Radiotherapy &Oncology Radio &O - Estro-members.org

ESTRO27 

September 14 – 18, 2008 

Göteborg, Sweden 

Volume Volume 88 Supplement 88 Supplement 2 September 2 September 2008 2008 ISSN 0167-8140 ISSN 0167-8140 

Radiotherapy 

&Oncology 

Journal Journal of the ofEuropean the European Society Society for for 

Therapeutic Radiology Radiology and Oncology 

and Oncology

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Volume 88 Supplement 2 (2008) 

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AIMS AND SCOPE 

Radiotherapy and Oncology publishes papers describing original research as well as review articles. It covers areas of interest relating to 

radiation oncology. This includes clinical radiotherapy, combined modality treatment, experimental work in radiobiology, chemobiology, 

hyperthermia and tumour biology, as well as physical aspects relevant to oncology, particularly in the field of imaging, dosimetry and radiation 

therapy planning. Papers on more general aspects of interest to the radiation oncologist including chemotherapy, surgery and immunology are 

also published. 

Clinical 

P. Scalliet 

Brussels, Belgium 

R.P. Abratt, Cape Town, South Africa 

K.K. Ang, Houston, TX, USA 

M. Bamberg, Tübingen, Germany 

A. Barrett, Glasgow, UK 

A.C. Begg, Amsterdam, The Netherlands 

S.M. Bentzen, Madison, WI, USA 

S. Bodis, Zrich, Switzerland 

M. Bolla, Grenoble, France 

T. Bortfield, Boston, MA, USA 

J. Bourhis, Villejuif, France 

P. Boyle, Milan, Italy 

M. Brada, Surrey, UK 

R.G. Bristow, Toronto, ON, Canada 

J.M. Brown, Stanford, CA, USA 

V. Budach, Berlin Germany 

F.A. Calvo, Madrid, Spain 

N. Coleman, Bethesda, MD, USA 

J.M. Cosset, Paris, France 

Physics 

D. Thwaites 

Leeds, UK 

EDITOR-IN-CHIEF 

Jens Overgaard, Aarhus, Denmark 

EDITORS 

Biology 

A.J. van der Kogel 

Nijmegen, The Netherlands 

PAST EDITORS 

Brachytherapy 

R. Pötter 

Vienna, Austria 

E. van der Schueren, Leuven, Belgium; H. Bartelink, Amsterdam, The Netherlands 

J.D. Cox, Houston, TX, USA 

L. Cozzi, Bellinzona, Switzerland 

B.J. Cummings, Toronto, ON, Canada 

O. Dahl, Bergen, Norway 

J. Denham, Waratah, Australia 

K. Dinshaw, Bombay, India 

S. Dische, Northwood, UK 

C. Fiorino, Milan, Italy 

Z. Fuks, New York, NY, USA 

J.P. Gérard, Lyon, France 

B. Glimelius, Uppsala, Sweden 

V. Grégoire, Bruxelles, Belgium 

J. Harris, Boston, MA, USA 

J.H. Hendry, Vienna, Austria 

M. Hiraoka, Kyoto, Japan 

J.Cl. Horiot, Dijon, France 

A. Horwich, London, UK 

R. Hunter, Manchester, UK 

EDITORIAL BOARD 

J. Jassem, Gdansk, Poland 

J.H.M. Kaanders, Nijmegen, The Netherlands 

T.J. Keane, Vancouver, Canada 

T. Kinsella, Madison, OH, USA 

J. Kurtz, Geneva, Switzerland 

P. Lambin, Heerlen, The Netherlands 

E. Lartigau, Lille, France 

J.W.H. Leer, Nijmegen, The Netherlands 

C.C. Ling, New York, NY, USA 

F. Macbeth, Cardiff, UK 

B. Maciejewski, Gliwice, Poland 

B.J. Mijnheer, Amsterdam, The Netherlands 

M. Molls, Munich, Germany 

J. Novotny, Prague, Czech Republic 

F. Nüsslin, Tübingen, Germany 

D.R. Olsen, Oslo, Norway 

L.J. Peters, Melbourne, Vic., Australia 

P. Poortmans, Tilburg, The Netherlands 

Education 

M. Baumann 

Dresden, Germany 

H.P. Rodemann, Tübingen, Germany 

J.Cl. Rosenwald, Paris, France 

M. Saunders, Northwood, UK 

W. Schlegel, Heidelberg, Germany 

W.U. Shipley, Boston, MA, USA 

M. Stuschke, Essen, Germany 

H.D. Suit, Boston, MA, USA 

H. Svensson, Umea˚, Sweden 

I. Tannock, Toronto, ON, Canada 

H. Thames, Houston, TX, USA 

A. Timothy, London, UK 

I. Turesson, Uppsala, Sweden 

W. Van den Bogaert, Leuven, Belgium 

A. van Oosterom, Leuven, Belgium 

H. von der Maase, Aarhus, Denmark 

H.R. Withers, Los Angeles, CA, USA 

B.G. Wouters, Maastricht, The Netherlands 

D. Zips, Dresden, Germany 

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CONTENT 

Abstract Spanish – Portuguese and Latin-American Association Day 

Monday, September 15, 2008 

Teaching lecture 

Evidence based medicine: bladder cancer (Abs. 1) 

Quality systems in radiotherapy (Abs. 2) 

Functional imaging and dose painting in prostate cancer (Abs. 3) 

DNA damage repair and signaling responses: new developments and clinical potential (Abs. 4) 

PET and PET/CT technology for RT (Abs. 5) 

Limitations of standard dosimetry methods in modern radiotherapy: from small to novel beams (Abs. 6) 

Acute radiation therapy effects in head & neck cancer (Abs. 7) 

Symposium 

BIOCARE (Abs. 8-11) 

Interdisciplinary treatment of locally advanced prostate cancer (Abs. 12-14) 

Shaping the RT future: clinical and technology (Abs. 15-18) 

New radiobiology insights applicable to brachytherapy (Abs. 19-21) 

Cancer stem cells and impact for clinical radiotherapy (Abs. 22-24) 

Biological target volumes and dose painting (Abs. 25-27) 

Challenges in the dosimetry of the new beams (Abs. 28-31) 

Head and neck cancer: skin and mouth care and diet (Abs. 32-34) 

High Risk Prostate Cancer (Abs. 35-38) 

Shaping the radiotherapy future: development of radiation oncology (Abs. 39-41) 

Partial breast irradiation (Abs. 42-44) 

Next steps in molecular targeting for radiotherapy (Abs. 45-48) 

Adaptive strategies in IGRT (Abs. 49-52) 

Tomotherapy and IMAT (Abs. 53-56) 

Use of PET/CT for radiation treatment planning (Abs. 57-59) 

Presidential Symposium (Abs. 60-62) 

Proffered paper 

Phase III randomised trials (Abs. 63-65) 

DNA-repair and signal transduction (Abs. 66-71) 

Adapting Optimized Therapy (Abs. 72-77) 

Applied dosimetry (Abs. 78-83) 

Treatment of cancer in H&N region and CNS (Abs. 84-88) 

Poster discussion 

Poster Discussion - physics (Abs. 89-109) 

Debate

The house believes that IGRT is the treatment of choice for T2 prostate carcinoma in a 60 y old man (Abs. 110-113) 


Clinical Lung (Abs. 114-119) 

BT Physics (Abs. 120-125) 

Molecular Targeting and Radiosensitization (Abs. 126-131) 

Physics Treatment technologies (Abs. 132-137) 

Rotational therapy (Abs. 138-143) 

Treatment of cancer in the thoracic region (Abs. 144-149) 

Quality of Life (Abs. 150-154) 

Award lecture 

Honorary Members (Abs. 155-157) 

Tuesday, September 16, 2008 


Screening, prevention and vaccination for cervical cancer (Abs. 158) 

Target Volume Selection and Delineation in Head and Neck tumors: beyond ICRU definition. (Abs. 159) 

3D image guided brachytherapy in head and neck cancer. Techniques and Benefits (Abs. 160) 

New developments in cell death: autophagy, senescence and the rest (Abs. 161) 

Multimodality imaging and registration (Abs. 162) 

Dose verification in advanced radiation therapy - New ESTRO Booklet (Abs. 163) 

Evidence based medicine: GI tumours (Abs. 164) 

Young scientist session 

How to write/submit a paper (Abs. 165-166) 

Symposium 

Clinical evidence for adjuvant radiotherapy for cervix and endometrial cancer (Abs. 167-169) 

Challenges in dose escalation in head and neck radiation oncology (Abs. 170-172) 

Advanced Treatment Planning in brachytherapy (Abs. 173-175) 

Mechanisms and treatment of normal tissue damage (Abs. 176-178) 

Protons/heavy ions/BNCT (Abs. 179-181) 

Modern dose calculation methods in radiation oncology (Abs. 182-184) 

Management of upper GI tumors (Abs. 185-187) 


Evidence Based Medicine (Abs. 188-190)

Symposium 

Definitive treatment in cervix and endometrium cancer: new horizon (Abs. 191-193) 

What is the standard of care for unresected locally advanced HNSCC? (Abs. 194-196) 

Volume effects in image guided brachytherapy (Abs. 197-199) 

Altered fractionation and impact on local control: future developments (Abs. 200-202) 

All you need to know about Hadron therapy (Abs. 203-206) 

Targeted radionuclide therapies (Abs. 207-209) 

Management of lower GI tumors (Abs. 210-212) 


Young Poster Session (Abs. 213-263) 


Gastro-intestinal Tumors (Abs. 268-273) 

Head & Neck I (Abs. 274-279) 

BT Gynaecology (Abs. 280-285) 

Normal Tissue Radiobiology (Abs. 286-291) 

Clinical aspects of hadron therapy (Abs. 292-297) 

Treatment planning and optimisation (Abs. 298-303) 

Treatment of cancer int the pelvic region (Abs. 304-308) 

Clinical Validation of Imaging (Abs. 309-314) 

Breast cancer (Abs. 315-320) 

Debate 

This house believes that the treatment of choice for loco-regional recurrence after concomitant chemo-radiotherapy 

in HNSCC is salvage surgery and post-operative re-irradiation (Abs. 321-323) 


Brachytherapy (Abs. 324-329) 

Treatment Techniques (Abs. 330-335) 

Physics aspects of Hadron therapy (Abs. 336-341) 

Dose Calculation (Abs. 342-347) 

Treatment Planning and Verification (Abs. 348-352) 

Social structure, risk management and other aspects (Abs. 353-358) 

Award lecture 

Breur lecture (Abs. 359) 


Highlights of the proffered papers (Abs. 360-362)

Wednesday, September 17, 2008 


Biologic basis for re-irradiation and current clinical concepts (Abs. 369) 

New irradiation techniques for breast cancer (Abs. 370) 

Symposium 

MAESTRO European Project: Innovations for planning and delivering of the RT treatment (Abs. 371-374) 


Molecular diagnosis and prediction: genome wide methods and potential (Abs. 375) 

MR imaging technology for radiation oncology (Abs. 376) 

The evolution of Linac technology for stereotactic radiosurgery (Abs. 377) 

Evidence based medicine: CNS tumours (Abs. 378) 

Symposium 

Is there still a role for radiotherapy in paediatric oncology? (Abs. 379-381) 

Tailoring for breast cancer radiotherapy (Abs. 382-384) 

ESMO/ESSO/ESTRO - State of the art in the management of rectal cancer I (Abs. 385-387) 

Tumor microenvironment and radiation response (Abs. 388-390) 

4D RT and respiratory gating (Abs. 391-394) 

Stereotatic body irradiation (Abs. 395-398) 

Management of gynaecological tumours (Abs. 399-401) 

Advances in the management of malignant glioma (Abs. 402-404) 

IMRT for breast cancer: a new standard? (Abs. 405-407) 

ESMO/ESSO/ESTRO - State of the art in the management of rectal cancer II (Abs. 408-410) 

Molecular imaging: from structures to treatment planning (Abs. 411-413) 

Respiratory surrogates and tumour motion (Abs. 414-417) 

Biological modelling in radiation oncology (Abs. 418-420) 

Late effects of radiation treatment - Psychosocial care (Abs. 421-423) 

Award lecture 

Regaud lecture (Abs. 424) 


Phase III randomised trials II (Abs. 425-426) 

Molecular biology in head and neck cancer (Abs. 427-431) 

Prediction and Genomics (Abs. 432-437)

Debate 

How much QA should be done for new radiotherapy technologies? (Abs. 438-440) 


Professional Development (Abs. 441-445) 

Symposium 

GENEPI 2 (Abs. 446-448) 


Prostate cancer (Abs. 449-454) 

Head & Neck II (Abs. 455-460) 

Target delineation (Abs. 461-466) 

Hypoxia and Vasculature (Abs. 467-472) 

Motion and uncertainties (Abs. 473-478) 

Clinical dose measurements (Abs. 479-484) 

Symposium 

GENEPI LOW RT (Abs. 485-487) 

Award lecture 

Varian/Fowler/Accuray (Abs. 488-491) 

Van der Schueren Award (Abs. 492) 

Thursday, September 18, 2008 


Evidence based medicine: anal cancer (Abs. 493) 

Cancer epidemiology (Abs. 494) 

MicroRNA and cancer (Abs. 495) 

Impact of new RT technology on margins (Abs. 496) 

Evidence based medicine: gynaecological tumours (Abs. 497) 

Quality management of ion beam therapy (Abs. 498) 

Evidence based medicine: prophylactic cranial irradiation (Abs. 499) 

Symposium 

New trends in the treatment of gastric cancer (Abs. 500-503) 

Waiting time in radiotherapy - Does it matter? (Abs. 504-508) 

Combining radiotherapy and immunotherapy: new concepts (Abs. 509-511)

Revisiting the concept of margins in treatment planning (Abs. 512-514) 

Management of CNS tumours (Abs. 515-517) 

Quality aspects of IGRT (Abs. 518-521) 

Omics, 4D and PET in radiotherapy for stage I-III NSCLC (Abs. 522-525) 

New trends in the treatment of pancreatic cancer (Abs. 526-528) 

Evidence based IMRT (Abs. 529-532) 

Radiation-induced secondary cancer: revisiting the field (Abs. 533-535) 

Treatment plan optimisation (Abs. 536-538) 


Treatment of prostate cancer (Abs. 539-544) 

Symposium 

Reliability of IGRT (Abs. 545-547) 

Treatment individualization in patients with SCLC treated by radiation therapy (Abs. 548-550) 

Debate 

Will all radiation therapy be proton therapy in 10 years from now? (Abs. 551-552) 

Posters 

Clinical/Disease sites : Brachytherapy techniques (Abs. 553-581) 

Clinical/Disease sites : Breast (Abs. 582-631) 

Clinical/Disease sites : CNS (Abs. 632-674) 

Clinical/Disease sites : Gastrointestinal tumors (Abs. 675-738) 

Clinical/Disease sites : Gynaecological tumours (Abs. 739-771) 

Clinical/Disease sites : Head and neck (Abs. 772-859) 

Clinical/Disease sites : Lung (Abs. 860-916) 

Clinical/Disease sites : Other tumor sites (Abs. 917-932) 

Clinical/Disease sites : Others (Abs. 933-947) 

Clinical/Disease sites : Paediatrics (Abs. 948-953) 

Clinical/Disease sites : Palliation/Supportive care/Patient support (Abs. 954-975) 

Clinical/Disease sites : Prostate (Abs. 976-1086) 

Clinical/Disease sites : Sarcoma, (Abs. 1087-1095) 

Clinical/Disease sites : Target and volume definition and delineation (Abs. 1096-1131) 

Physics and technology : Adaptive and image/dose guided RT (Abs. 1132-1186) 

Physics and technology : Applied dosimetry e.g. EPID, Gel, quality assurance (Abs. 1187-1240) 

Physics and technology : Basic dosimetry and detectors (Abs. 1241-1261) 

Physics and technology : Dose calculations (monitor calc, Monte Carlo, TPS) (Abs. 1262-1303) 

Physics and technology : Optimization and dose planning (Abs. 1304-1334) 

Physics and technology : Others (Abs. 1335-1345) 

Physics and technology : Patient immobilization/Positioning (Abs. 1346-1375) 

Physics and technology : Protons and ions (Abs. 1376-1384) 

Physics and technology : Treatment techniques, modalities and technology (Abs. 1385-1422) 

Radiobiology : Combined chemo/targeted agents and radiotherapy (Abs. 1423-1428) 

Radiobiology : DNA repair (Abs. 1429-1433) 

Radiobiology : Genomics and proteomics (Abs. 1434-1437) 

Radiobiology : Hypoxia and angiogenesis (Abs. 1438-1440)

Radiobiology : Normal tissue morbidity (Abs. 1441-1459) 

Radiobiology : Others (Abs. 1460-1479) 

Radiobiology : Predictive assays/Prognostic factors (Abs. 1480-1498) 

Radiobiology : Radiosensitisers (Abs. 1499-1501) 

Radiobiology : Signal transduction (Abs. 1502) 

Radiobiology : Time dose fractionation (Abs. 1503-1510) 

RTT (Abs. 1511-1538) 

Social, structural, logistics and other aspects of RO : Education and training (Abs. 1539-1545) 

Social, structural, logistics and other aspects of RO : Others (Abs. 1546-1548) 

Social, structural, logistics and other aspects of RO : Risk and quality management (Abs. 1549-1556)

Ab s t r A c t spA n i s h – po r t u g u e s e A n d LAt i n-Am e r i cA n As s o c iAt i o n dAy

1 oral 

HIGH EXPRESSION OF EPIDERMAL GROW FACTOR RECEPTOR 

IS A PROGNOSTIC FACTOR OF OVERALL SURVIVAL IN CERVIX 

CARCINOMA 

Elena Villafranca, Gemma Asin, Rosa Guarch, Pilar Romero, Fernando 

Arias, Ana Manterola, Enrique Martinez, Mikel Rico, Meritxel Vila, 

Miguel Angel Dominguez 

PurPose : to evaluate EGFR as a prognostic factor of survival, in biopsy 

of patients with cervix carcinoma (CC) treated at our Center with 

Chemo-Radiotherapy and High-Dose-Rate Brachytherapy (HDR-B). 

Material and Methods : Between July/2001 and September/2007 

were treated at our Center a total of 37 women with CC. Treatment 

consisted of radiotherapy (45 Gy at 1.8Gy per fraction) and 

concomitant chemotherapy (cisplatin, 40 mg/m2 weekly), followed 

by HDR-Brachytherapy (6 Gy/fx 5 fx on A point). Finally, all patients 

received a parametrial boost to a total dose of 60-66 Gy. 

EGFR were analized in 18 p. by Inmunohistochemist (IHC) : Grade 0 : 

no tincture; Grade 1 :50%). 

results : The study of EGFR could be done in 23 p. Characteristics 

of the series : stages : IIA-IIB : 11p (47%), IIIB-IVA : 4p (18%); N1( clinical 

or pathological by lymphadenectomy) : 8p (35%). 

Five-year overall survival for EGFR+++ was 0% (median of 21 months) 

against 76% in the group of EGFR 0/+/++ (median 64 months)(p=0.002). 

By multivariate analysis (Cox Regression), EGFR+++ was an independent 

prognostic factor of survival : HR : 8.1; IC 95 % : 1.8-35; p= 0.005. 

ConClusion : In our experience, EGFR expression was an important 

prognostic factor for survival of patiens with CC treated with Chemoradiotherapy 

and brachytherapy. Patiens with EGFR +++ had a risk 

8 times superior of mortality by cervix cancer. Targeted therapy 

against EGFR may be usefull in those patients. 

2 oral 

INFLUENCE OF APPLICATORS DESIGN ON THE QUALITY OF HIGH 

DOSE RATE INTRACAVITARY BRACHYTHERAPY INSERTIONS FOR 

WOMEN WITH CERVICAL CANCER 

De Melo M.D., Balloni H., Novaes P.E.R.S, Castro D.G, Teixeira G.N, 

Fogaroli R.C., Maia M.A.C, Pellizon A.C., Hanriot R., Salvajoli J.V. 

De p a r t a m e n t o D e ra D i o t e r a p i a - Ho s p i t a l a C Ca m a r g o – sã o pa u l o - Br a s i l 

PurPose : To investigate the impact of the applicators design in the 

quality of high dose rate intracavitary brachytherapy treatment for 

women with cervical cancer. 

Materials : We analyzed 836 intracavitary brachytherapy 

insertions for women with cervical cancer between November 2002 

and July 2006. There were two types of Fletcher applicators available 

in that time : Nucleotron and GammaMed. The treatment proceeded 

in an ambulatorial fashion without the use of routine anesthesia. In 

every insertion, the patients had two orthogonal radiographs for 

individual planning and dose optimization definition. They were 

treated in the same position of the X-Rays (gynecological). There 

were analyzed the differences between the insertions achieved 

with the two applicators for : the length of the uterine tandem 

(hysterometry), size of the vaginal colpostats, rectal and vesical 

shielding thru vaginal packing and the incidence of intercurrences. 

results : The median age for the entire population was 54 years. 

There were 284 insertions with Nucletron applicators and 553 

with GammaMed ones. There was no different related to the type 

of the applicator in median dose delivered to point A (6.6Gy x 

6.7Gy - p=0.2), hysterometry (57mm x 58mm - p=0,7) or neither 

intercurrences (10 x 11% - p=0.57). There was significant difference 

of the ovoid size used between the models. The use of mini-ovoid, 

small ovoid (2cm diameter) and median ovoid (2,5cm de diameter) 

was 7%, 66%, 2,8%, respectively for Nucletron and 30%, 42%, e 6,5% 

for GammaMed (p = 0.006 for mini vs others). The use of vaginal 

cylinder was similar between the two grups (23% x 18%, p=0.6). 

Vaginal packing was more common with GammaMed (62% vs 32%, 

p=0.001) probably because Nucletron model has an intrinsic device 

for rectal protection. 

ConClusion : The model design of different applicators can have 

an intrinsic relation with the better insertions geometry possible for 

intracavitary gynecological brachytherapy. The more common use 

of greater diameter ovoid with one of the models can decrease de 

dose received on the vaginal mucosa and expand the prescribed 

isodose volume, probably improving the quality of the treatment. 

3 oral 

EVALUATION OF SURGICAL RESECTION IN PATIENTS WITH LOCALLY 

ADVANCED CERVICAL CARNINOMAS AFTER NEOADYUVANT 

CHEMORADIOTHERAPY AND BRACHYTHERAPY OF HIGH DOSE 

RATE (HDR). 

Mª Carmen Salas Buzón, Lucía Gutierrez Bayard, Laura Díaz, Gloria 

Reina Vinardell. Ho s p i t a l universitario pu e r t a D e l ma r, Cá D i z 

objeCtive : The aim of this study was to evaluate the surgical 

resection on young patients of locally advanced cervical carcinoma 

in terms of morbility, tumoral control and survival, after neoadyuvant 

chemoradiotherapy and endouterine brachytherapy of High Dose 

Rate was applied 

Patients and method : Between January 2001 and February 2008, 

we evaluated 24 patients, with locally advanced cervical carcinomas 

considered as bulky and with clinical condition FIGO : Ib2 :1, IIB :15, 

IIAB :2, IIIA :2, IIIAB : 4. The age mean of these patients was 48 years 

of age (range 31-50). Clinical tumoral size mean was 5 cm (range 4.5- 

7cm). Pelvic nodes clinically positive were observed in 8 (38%) of the 

patients. Virtual simulation after helicoidal CT slides (0.5 cm) and 3D 

planning were taken. All patients received external pelvic radiotherapy 

with photons of 15 Mv. Concomitant weekly chemotherapy (o 

chemoradiotherapy?) with Cis-Platinum treatment was applied. The 

average pelvic dose was 49 Gy (range 45-50.4) administered over a 

five week period. 21 patients (87%) were administered intracavitary 

brachitherapy of high dose rate with Iridium – 192, dose of 10 Gy, with 

an average of two presurgical application. After a 5-6 week period, all 

patients underwent a modified radical histerectomy Class II, while 

15 patients (62%) with 7 isolated nodes on average (range : 4-20), 

underwent bilateral pelvic lymphadenectomy. The follow-up mediam 

was 62 months (range 23-85). 

results : The rate of complete pathological response was 42% . 

Residual tumor was observed in 14 (58%) patients. Of the residual 

tumor patients (1 cm. : 4 y > 2 cm : 5) all but 3 with 2 cm 

residual tumor received High Dose Rate (Ir 192) on average of 2,7 

fractions of 5Gy with tandem and ovoid application (Fletcher System) 

preoperative brachytherapy. One patient (Ib2) present a positive 

pelvic node (1+/9). Another patient who dsiplayed microscopic 

residual vaginal tumor, was treated with two postoperatory 

endovaginal brachytherapy fractions with dome and cylinders. 

Pathological parametrial infiltration was not detected in any of the 

patients. Every patient completed at least 5 cycles of Cisplatinum 

weekly. The hematological toxicity was moderate with 2 episodes 

of transitory plachetopenia. The maximum acute gastrointestinal 

morbidity to the radiotherapy was G : 2 (RTOG). 

A vesico-vaginal fistula observed in a patient was resolved spontaneously, 

two months after surgery, secondary to the pelvic fibrosis. 

The 3 and 5 year overall survival was 87% and 79% respectively. The 

3 and 5 year disease free survival was 79%. After a multivariated 

analysis, the only independent factor that dicreased the disease free 

survival and the overall survival was the presence of pathological 

residual tumor in the surgical specimen. 

ConClusion : Surgery after chemoradiotherapy may have a place 

within the multimodal treatment in young patients with locally 

advanced cervical carcinomas, especially in the case of tumors 

considered bulky. In selected cases, it may be used with acceptable 

morbidity, being essential the use of intracavitary brachytherapy.

4 oral 

LOCAL CONTROL RESULTS OF RADICAL RADIOTHERAPY OF CERVICAL 

CANCER. OUR EXPERIENCE 

Dávila-Fajardo R¹, López-Soler FJ¹, González-López A², De La Fuente- 

Munoz I¹, García-Fernández R¹, Salinas J¹, Porras M¹, Fernández-Pérez J¹ 

¹raDiation on C o l o g y (Ho s p i t a l u.vi r g e n D e la ar r i x a C a - mu r C i a), ²raDiopHysiCs 

a n D ra D i o p r o t eC t i o n (Ho s p i t a l u.vi r g e n D e la ar r i x a C a - mu r C i a) 

PurPose : To show the local control results and toxicity events 

of our patients suffering from a cervical cancer who were treated 

combining External Beam Radiotherapy (EBRT) with or without 

chemotherapy and Brachytherapy-High Dose Rate (HDR-BT) as 

radical treatment. 

Material/Methods : From May 2006 to May 2008, 14 patients (p), 

11 epidermoid cervical cancer and 3 adenocarcinoma, stage IB2 (1p)- 

IIA (2p)-IIB (8p) and IIIB (3p), received pelvic 3D-EBRT (46-50Gy); 8 of 

them underwent paraortic 3D-EBRT (44-45Gy), and 4 parametrium 

boost. Eleven of them followed concurrent chemotherapy (Cisplatin 

40mg/m²/w). HDR-BT (MicroSelectron) was delivered afterwards, 

under spinal anaesthesia; 12 patients received 24Gy and the rest 

received 20Gy (4 fractions). 

results : Four patients underwent rescue surgery (radical 

hysterectomy), 2 pathological complete response (14%) and 2 stage 

pT1a (14%). Seven patients (50%) had complete response (Citology, 

PET-Scan and MRI), two of them progressed (one metastatic 

subcutaneous implant ( 7%) and one paraortic lymph node (out of 

fields) (7%)). One patient was lost during the follow-up and two are 

already undergoing the staging study after treatment. In terms of 

toxicity treatment was well tolerated. We experienced during EBRT 

one G2 and one G3 cases of intestinal toxicity, and nine G1 cases 

of urinary toxicity. While BT no rectal toxicity and two G2 cases of 

urinary toxicity. 

ConClusion : EBRT with or without concurrent chemotherapy 

followed by HDR-BT as radical treatment in cervical cancer is a good 

option in terms of local control and tolerance. Sometimes rescue 

surgery can be needed. A wider number of patients and long-term 

clinical results are needed. 

5 oral 

“HIGH-RESOLUTION 1H NMR SPECTROSCOPY STUDIES OF 

PERCHLORIC ACID EXTRACTS OF CERVIX CARCINOMA AND CERVIX 

NORMAL MUCOSA” 

M Abreu Roldão, T.Lopes *, R.Cavas-Altas *, J. Moura *. 

in s t i t u to po r t u g u ê s on C o l o g i a D e li sB o a Fr a n C i sC o ge n t i l, Fa C u l D a D e CiênCias 

te C n o l o g i a*, un i v e r s iD a D e no v a D e li sB o a. 

PurPose : To develop the analytical chemistry study with magnetic 

resonance spectroscopy of carcinoma of the uterine cervix in order 

to more effectively identified risk factors that may improve the 

management of patients with cervical carcinoma so that we may apply 

more aggressive therapeutic strategies to those with poor prognosis. 

Material and Methods : Perchloric acid (PCA) extraction was 

performed on frozen 95 tissue samples obtained by biopsy of 80 

cervical carcinomas and of 15 normal uterine cervix. The samples 

were obtained before the patients were submitted to any therapy. 

We examined all these PCA extracts with 1H NMR spectroscopy 

and we obtained 95 spectra at 400 MHz on a Bruker ARX 400 

spectrometer. A qualitative characterization of the aliphatic and 

of the aromatic regions of the PCA extract spectra was carried 

out. With the integrated peak areas of the different metabolic 

substances identified (leucine, isoleucine, valine, threonine, lactate, 

alanine, lysine, acetate, glutamine, glutamate, proline, succinate, 

creatine, choline, glycine, taurine, inositol,serine, nucleotides and 

related compounds) we established several ratios and used them to 

correlate with the known prognostic factors of the carcinoma of the 

uterine cervix. 

results : Abnormal metabolism in the tumours gave increased 

levels of almost the metabolites analyzed. Statistically significant 

differences between the cancer and benign groups were seen 

for the levels of leucine, isoleucine, valine, alanine, lysine, proline, 

creatine, choline, taurine, inositol, cytosine, adenine and also for the 

metabolite peak area ratios of leucine, isoleucine, valine to alanine, 

creatine to alanine, creatine to choline, inositol to taurine, inositol to 

creatine and inositol to alanine; the difference of the metabolite peak 

area ratio of inositol to taurine was statistically significant when we 

compared the cancer samples in relation to histology, stage, tumour 

volume and haemoglobin level. 

ConClusion : The performance of 1H NMR spectroscopy in 

biopsies of carcinoma of the cervix is readily accomplished and the 

proposed methodology in the near future may be translated into a 

more accurate definition of prognostic indicators in this disease, an 

approach that potentially should result in improved therapy. 

6 oral 

ADENOCARCINOMA OF THE UTERINE CERVIX : PROGNOSIS, 

TREATMENT AND PATTERNS OF FAILURE. 

M. Abreu Roldão, F. Santos, I Cabral, J. Faria, S. Macedo. 

se r v i ç o D e ra D i o t e r a p i a, in s t i t u to po r t u g u ê s D e on C o l o g i a D e li sB o a Fr a n C i sC o 

ge n t i l (ipol), epe, li sB o a. 

PurPose : Controversy continues between advocates of radical 

surgery and radiation therapy. The combination of external beam 

radiation therapy ± chemotherapy, brachytherapy and surgery is 

the standard of care in the management of adenocarcinoma of the 

cervix. According to the tumour stage brachytherapy is indicated 

before or after surgery or is associated to external irradiation ± 

chemotherapy. The aim of this study is to investigate the influence 

of prognostic factors and, the impact of cervix cancer brachytherapy 

combined with external beam radiotherapy ± chemotherapy on 

local control, overall survival, disease free survival and morbidity in 

a consecutive cohort of 218 patients with adenocarcinoma of the 

uterine cervix treated at our institution. 

Materials and Methods : Between 1995 and 2005, 2203 patients 

with cervix uteri carcinoma were treated with radiotherapy at the 

IPOL. Histologically 218 were adenocarcinomas with a mean age 

of 54.6 years. Of the 218 patients 65 had International Federation 

of Gynaecology and Obstetrics (FIGO) stage IB1, 33 had stage IB2, 

55 had stage IIA, 37 had stage IIB, 22 had stage III, and 6 had stage 

IV disease; 39 cases were treated with external irradiation alone, 

whereas intracavitary brachytherapy was added in 51 patients; 37 

cases did surgery, with external irradiation and brachytherapy or 

with external irradiation only (14) or with brachytherapy only (36). 

We started to treat with concomitant chemo-radiotherapy in 2001, 

and 15 patients did combined therapy with external irradiation, and 

17 patients did combined therapy with external irradiation plus 

brachytherapy; surgery was added in 23 of these cases. 

Results : Median follow-up time was 53 months. The disease free and 

overall survival at 5 years was 69.7% and 68.7% respectively. Overall 

survival by stage was 82.1% IB1, 78.8% IB2, 56.3% IIA, 37.8% IIB, 37.3 

III and 0% IV. 

ConClusions : Patients with small volumes lesions have excellent 

local regional control and survival. Radiotherapy achieves good 

local regional control, but survival decrease with increasing primary 

tumour size. Concurrent chemo-radiotherapy is well tolerated and 

produces also excellent local control. Further studies are needed 

to better define the role neo-adjuvant and adjuvant therapy in 

adenocarcinoma of the uterine cervix.

7 oral 

RADIOBIOLOGICAL ANALYSIS OF RADIATION TREATMENTS IN 

PROSTATE CANCER BASED ON EQUIVALENTE UNIFORME DOSE 

(EUD) : BRACHYTHERAPY VS. EXTERNAL RADIOTHERAPY 

Victor Bourel, universiDaD Fa v a l o r o, Bu e n o s ai r e s, ar g e n t i n a 

Marcela de la Torre, CeDete, Bu e n o s ai r e s, ar g e n t i n a. 

PurPose : The objective of the work is to analyze and to compare 

different radiation treatment modalities (Brachytherapy LDR and 

Externa Radiotherapy 3D) from a radiobiological point of view. 

Material and Method : 60 patients (30 brachytherapy - 30 

external radiotherapy 3D) were analyzed from the three-dimensional 

data obtained with treatment plannings. The average prostate 

volume (without margin) was 34.8 cm3. 

The brachytherapy was carried out guided with ultrasound with I-125 

in real time prescribing 145 Gy to the target volume obtained like the 

prostate volume plus a margin of 3 mm. The external radiotherapy 

was carried out with 6 Mev photons with 6 conformed fields to the 

target volume obtained like the prostate volume plus a margin of 8 

mm in the 3 directions with manual correction in rectum and bladder. 

The isocenter dose was 77.4 Gy with a daily fraction of 1.8 Gy. 

The radiobiological analysis was made based on the calculation 

of Equivalent Uniform Dose (EUD) and using the Linear-Quadratic 

model to obtain the survival fraction in brachytherapy and external 

radiotherapy. The parameters used in the Linear-Quadratic model 

for prostate tissue were α = 0.15 Gy-1, α/β = 3.1 Gy, μ = 62.38 days-1 

and γ = 0.0165 day-1. 

The survival fraction was estimated like S = Σ (vi /vo ) . S (Di ). Where 

vi it is partial volume and Di is the equivalent dose to 1.8 Gy/fr. These 

values are taken from the respective Dose-Volume Histograms. 

results : The average EUD in patients treated with Brachytherapy 

was 74.1 Gy and the average EUD in patients treated with External 

Radiotherapy was 76.4 Gy. This result imply a tumor control 

probability (TCP) value of 91% and 94% for low risk patients and 

83% and 89% respectively for intermediate risk patients. 

ConClusion : With the uncertainty associated to the used 

radiobiological parameters, with the present levels of knowledge, 

it is possible to consider that the described treatments are 

radiobiologically equivalent. 

The used methodology of calculation can be applied to the 

comparison of any modality of radiation treatment. 

8 oral 

SPANISH EXPERIENCE WITH TOMOTHERAPY IN PROSTATE CANCER. 

Morera López, Rosa. Matute, Raúl. Delgado, José Miguel. Minguez, 

Cristina. Beltrán, César. Departament Radiation Oncology. 

Tomotherapy. ClíniCa “la mi l a g r o s a”. gr u p o imo. ma D r iD. sp a i n. 

objeCtives : To evaluate the radiotherapy in patients with 

prostate cancer (PC) with a new technique of irradiation like is the 

Tomotherapy, that combines two important technological advances 

as they are, intensity modulated radiotherapy (IMRT) and the image 

guided radiotherapy (IGRT). 

Material and Methods : The first Unit of Tomotherapy in Spain 

is operative from Abril 2006. Since then and until Abril 2008 we have 

treated a total of 293 patients, of who, 37 patients had PC diagnosis. 

All the patients were put under from one week before the planning 

CT, medical and dietetic treatment to try to daily reduce and to 

reproduce the rectal volume during the treatment. 

results : The tolerance to the treatment with Tomotherapy was 

excellent in all the patients, not presenting severe acute toxicity. 

The technique of Tomotherapy has allowed us to obtain excellent 

conformations of dose, being diminished the dose in risk organs 

(OR). The daily accomplishment of the megavoltage CT has allowed 

to see the daily position errors and to quantify them, as well as 

changes in the form and volume of the prostate and still more of the 

OR observing that the variations of the rectal filling cause important 

dosimeter repercussions. A daily localization pre-treatment 

megavoltage CT scans allows us to act of active way on the rectal 

volume making adapted radiotherapy, avoiding serious dosimeter 

repercussions and assuring a suitable cover target. 

ConClusions : Our advocate the use of IGRT in the treatments of 

IMRT in PC. The Tomotherapy could improve the therapeutic index 

in PC. The dose reduction in OR and the geometric precision are a 

potential benefit this new technique, will make us develop towards 

the hypofractionation in the CP. It would be of great interest to initiate 

trials to evaluate the impact of dose escalation versus IGRT in PC. 

9 oral 

IMAGE GUIDED HIGH-DOSE-RATE BRACHYTHERAPY WITH LOCAL 

ANESTHESIA IN AN OUTPATIENT BASIS FOR LOCALLY ADVANCED 

PROSTATE CANCER COMBINED WITH HIPOFRACTIONATED 

EXTERNAL BEAM RADIOTHERAPY. ANALYSIS OF ACUTE MORBIDITY 

AND PAIN SCORE. 

Pellizzon ACA, Novaes PERS, Salvajoli JV, Fogaroli R, Maia MA, Hanriot 

R, Castro Dg De p a r t a m e n t o D e ra D i o t e r a p i a – Ho s p i t a l aC Ca m a r g o – sã o 

pa u l o - Br a s i l 

PurPose : There are two primary methods to deliver radiotherapy 

to the prostate : external-beam and brachytherapy. High dose rate 

temporary brachytherapy, performed with catheters implanted 

into the prostate, has been performed since 90´s and nearly all HDR 

patients have been treated under general or spinal anesthesia. One 

new alternative involves the use of local anesthesia and conscious 

sedation, in an outpatient basis and images acquisition for HDR tridimensional 

planning (IG-HDR) using trans-rectal ultrasound. 

Materials and Methods : 16 consecutive patients with a median 

age of 62 (46-69), grouped into intermediate or high risk with locally 

advanced prostate cancer were encouraged to participate in an 

institutional protocol combining IG-HDR and hypofractionated 

conformal external-beam radiotherapy. For IG- HDR treatments, patients 

were submitted to 2 implants with one week interval, with two fractions 

of 7.5 Gy given per implant. Planning was based on images acquired 

using the VITESSE software. We evaluated pain related to the procedure 

according to the University of California, Los Angeles, The Universal Pain 

Assessment Tool and acute morbidity (urinary and rectal) according to 

the RTOG scale. One week after the end of HDR-BT regimen, the patient 

begins the hypofractionated conformal external-beam radiotherapy 

(h-RT3D) plan, with 45 Gy given in 3-Gy daily fractions for 3 weeks, with 

a total treatment time of 5 weeks. 

results : To date, we have performed 32 implants in years using 

local anesthesia. In all cases, implants were completed as planned 

with no deviation. Pain score ranged from 2 (mild) to 6 (moderate), 

with a median score of 3 to 4 (mild to moderate). Prostate volumes 

ranged from 25 to 48 cm3 (mean, 33 cm3). The amount of lidocaine 

administered ranged from 250 to 500 mg, with a median of 300 mg; 

this amount varied according to perceived tolerance to injections 

and was fairly constant among patients. The incidence of acute 

urinary and rectal acute toxicity G1-2 were 3/32 (9,3%) and 1/32 

(3,1%). No grade 3-4 toxicity was observed. 

ConClusions : Prostate HDR with the patient under local 

anesthesia is a relatively efficient procedure in terms of resource 

use and personnel time, with acceptable rate of acute toxicity. 

Local anesthesia may facilitate and expand HDR to boost external 

beam radiotherapy for intermediate and high risk patients in limited 

resource countries with a lack of hospital beds..

10 oral 

TC VS TRUS IN HIGH DOSE RATE PROSTATE BRACHYTHERAPY : A 

COMPARATIVE STUDY 

C. A. M. Jesus*, I. Monteiro-Grillo*', L. M. V. Prudêncio*, M. Jorge*, M. Ruivo* 

*Ce n t r o Hos p i t a l a r lisB o a nor t e - Ho s p i t a l D e san t a mar i a, ‘Fa C u l D a D e D e 

meDiCina D e li sB o a 

Av. Prof. Egas Moniz, 1649-035 Lisboa, Portugal 

introduCtion : In recent years, High Dose Rate Prostate 

Brachytherapy (HDR BT) has become one of the techniques of 

choice in the treatment on prostate cancer both as a monotherapy 

and as boost for external beam irradiation. 

One of the goals of radiotherapy is to conform the dose distribution 

to the tumor, sparing adjacent organs; for that purpose, one has to 

rely on accurate knowledge of the particular anatomy of the patient. 

For this reason, in brachytherapy, as in external beam radiotherapy, 

it is no surprise that imaging techniques are becoming of increasing 

importance on the implementation of the technique. 

objeCtives : The purpose of this work is to evaluate the capacity of 

a system that is exclusively base on Ultra Sound imaging, to replace 

a CT based system for prostate HDRBT treatments. The system will 

be evaluated based on dosimetric criteria as well as logistics and 

patient comfort. 

Methods : Since 2006, 77 patients where subjected to BT HDR. In 

52 of those patients, the needles where placed using TRUS guidance, 

but the planning was done using CT images. In the remaining 

patients, both the implant and the dosimetry where done exclusively 

with TRUS imaging. In both cases, the final needle positioning was 

verified using fluoroscopy. 

results : There is a clear tendency to reduce the dose on the OAR 

when using TRUS as compared to CT for identical coverage of the 

target volume. The dosimetric parameters (V100, V150, D90 for the 

target and DMAX at the OAR) show in general a smaller dispersion 

from implant to implant when using TRUS. 

ConClusions : Using TRUS for the planning of Prostate HDR BT is a 

viable alternative to CT planning. High quality dosimetric results can 

be obtained and the entire process takes less time. This is of extreme 

importance since it decreases the possibility of errors due to the fact 

that there is no need to move the patient between the insertion 

of the needles, image acquisition and treatment, improving also, 

patient comfort. 

11 Poster 

Radiotherapy plus Cetuximab for squuamous- Cell Carcinoma of the 

Head and Neck. 

L. Gutiérrez Bayard; C. Salas Buzón; L. Diaz. on C o l o g y ra D i o tH e r a p y. 

Ho s p i t a l u. pu e r t a D e l ma r. Cá D i z. spain. 

PurPose : We performed a retrospective review study of patients 

treated with Radiotherapy and cetuximab, a monoclonal antibody 

against the epidermal growth factor receptor, in the treatment of 

locoregionally advanced squamous – cell carcinoma of the head 

and neck. 

Methods : 23 patients with locoregionally advanced head and neck 

cancer, insuitable for concurrent platinum based chemotherapy, 

were assigned to treatment with high-dose radiotherapy plus 

weekly cetuximab. The primary end point was the response rate, 

and safety. 

results : Median follow up for all patients at last contact was 11 

months. The locoregioanl control was 69.6%. Cetuximab, instead 

cisplatin, doesn´t increase acute toxicities including mucositis and 

dysphagia, however it´s associated with a characteristic acneiform 

rash. In this study skin reactions was grade 3 in one patient; grade 2 

in 18 cases, and grade 1 in four patients. 

ConClusions : In a retrospective review of patients with 

locoregionally advanced head and neck cancer treated with external 

radiotherapy to concurrent cetuximab is a safe regimen andf there 

didn´t appear to be differences in locoregional control. 

12 Poster 

SYNCHROTRON RADIATION THERAPIES (SRT) : A PROMISING 

ALTERNATIVE FOR TREATING BRAIN TUMORS 

Prezado Y. 

PurPose : The use of Synchrotron Radiation (SR) is an innovative 

tool for treating brain tumors. Conventional radiotherapy is only 

palliative for several brain tumor grades, because it is necessary to 

deliver a high therapeutic dose of ionizing radiation to the tumor 

without exceeding healthy tissue tolerances. This limitation is 

particularly severe in the case of brain tumors because of the high 

risk of adverse normal tissue morbidity. At the ESRF the research has 

focused on the treatment of high grade gliomas which are some of 

the most resistant and aggressive human tumors. 

Materials and Methods : 

At ESRF two new techniques are being developed : 

I. Stereotactic Synchrotron Radition therapy (SSRT) : 

The tumor is loaded with a high Z element (iodine or gadolinium) 

combined or not with a chemotherapic drug. The beam size is 

adjusted to the tumor dimensions, the tumor positioned at the 

center of rotation and the irradiation is performed over several 

incidences with kilo-voltage X-ray beam (80 keV). The therapeutic 

effect is increased by an enhanced local energy deposition due to 

secondary particles mainly generated by photoelectric effect on the 

high – Z atoms located in the tumor. 

II. Microbeam Radiation Therapy (MRT) 

MRT is carried out using narrow (~25 μm) rectangular beams placed 

at a distance of typically 200 μm from each other 

As first seen in Brookhaven by Curtis et al [1] the normal tissue 

tolerance to small micrometer sized radiation beams is very high. 

MRT has shown that can safely deliver radiation doses to healthy 

tissues that are much higher that the doses tolerated by the same 

normal tissue from one standard milimeter wide radiosurgical beam 

(2). MRT might be used to treat brain tumors in children with less 

risk to the development of the central nervous system than using 

wider beams (2). 

results : A extended life span in rats bearing brain tumors has 

been observed for both techniques, SSRT (3) and MRT (4) . Preclinical 

trials demonstrate that both MRT and SSRT techniques can achieve 

tumor control, with no (or limited) normal tissue damage. 

ConClusions : Based on the encouraging preclinical results 

obtained so far, clinical trials will start in 2008-2009 at ESRF. 

(1)Curtis et al., Radiat.Res. Suppl. 7, pp. 250-257, 1967 

(2)Laissue et al., Develop. Med & Child Neurology 2007(49) 577 

(3)Adam et al, Int. J. Radiation Oncology Biol. Phys. 64 (2006) 603. 

(4) Laissue et al., Int. J. Cancer 78 (1998) 654.

ABSTRACTS CONFERENCE

MONDAY, SEPTEMBER 15, 2008 TEACHING LECTURE 

Monday, September 15, 2008 


1 speaker 

EVIDENCE BASED MEDICINE: BLADDER CANCER 

M. Høyer 1 

1 AARHUS UNIVERSITY HOSPITAL, Department of Oncology, Aarhus C, 

Denmark 

In most Western countries, radical cystectomy is preferred over radiotherapy 

in treatment of muscle invasive stages of urinary bladder carcinoma and patients 

are only offered radiotherapy if they are unfit for surgery. A number of 

retrospective studies have shown that patients with urinary bladder cancer 

can be cured by radiotherapy. Local control rate after treatment is 60-70% 

and long term control is obtained in 40-50% of the patients. A large fraction 

of patients will have a systemic failure and dissemination at an early time point 

characterize the disease. 5-years survival rates are often 20-50%, between 

24-50% when patients who are primarily selected for radiotherapy and 8-31% 

when radiotherapy is reserved for unfit patients. The volume to be treated 

in radiotherapy of bladder cancer remains unclear. Target volumes vary from 

partial bladder to the whole bladder including regional lymph nodes. It is often 

claimed that elderly people with bladder cancer do not tolerate radiation to a 

large volume including the lymph node. In contrast, others find that irradiation 

of elective lymph nodes followed by a boost to the bladder is tolerated with an 

acceptable level of toxicity. Pathology studies conclude that the risk of lymph 

node metastases is closely related to the T-stage and the lymph node at risk 

are the commen-, internal iliac- and upper external iliac nodes. Most often, 

radiotherapy to bladder cancer is given with 2 Gy per fraction to a total dose of 

60 Gy. Increasing the dose with normo-fractionation has not improved the outcome 

and hypofractionation with biological high doses has not been proven 

beneficial. In a study on hyperfractionation, patients treated with a total dose 

of 84 Gy in 1 Gy fractions three times daily had better outcome compared 

to patients treated with a standard dose/fractionation schedule. However, this 

type of fractionation if only rarely used in treatment of bladder cancer. Bladder 

cancer is associated with a high risk of distant metastasis and neoadjuvant 

platin based chemotherapy have an effect on survival. Furthermore, a strategy 

including extensive transurethral resection of the bladder tumor combined 

with chemotherapy and radiotherapy has been introduced for the purpose of 

preserving the urinary bladder. In standard setting, an isotropic margin of 2 

cm to account for day-to-day changes in target position is applied to the bladder. 

However, some studies have shown that an anisotropic margin may be 

more optimal. Focal boost to the macroscopic bladder tumor or the tumor bed 

after resection may be a way to improve the local control without increasing 

the probability of late reactions. IGRT combined with on board correction of 

tumor position may be a way to give a focussed high dose boost to the bladder 

tumor. In lymph node irradiation, IMRT may be superior to conventional 

3- or 4-field techniques with sparing of the rectum and the bowel. 

2 speaker 

QUALITY SYSTEMS IN RADIOTHERAPY 

P. Scalliet 1 

1 UNIVERSITÉ CATHOLIQUE DE LOUVAIN, Department of Radiation Oncology, 


Abstract not received. 

Functional imaging and dose painting in prostate 

cancer 

3 speaker 

FUNCTIONAL IMAGING AND DOSE PAINTING IN PROSTATE 

BRACHYTHERAPY 

P. Hoskin 1 , R. Alonzi 1 

1 MOUNT VERNON HOSPITAL, Cancer Centre, Northwood Middlesex, United 

Kingdom 

Radical radiotherapy is an effective treatment for localised prostate cancer. 

Tumour control shows a dose response. Dose escalation may be best 

achieved using brachytherapy. Currently the planning target volume (PTV) 

is defined as either the whole prostate or the peripheral zones. This does 

not however take into account either the distribution of tumour or potential 

areas of resistant tumour in targeting the dose to the most radioresistant 

cells. It is now possible to define the geographical extent of prostate cancer 

and many of its physiological characteristics using functional imaging. 

MR scanning can identify the distribution of tumour using T2 weighted se- 

quences and diffusion weighted imaging. This is also possible using magnetic 

resonance spectroscopy and 11C choline positron emission tomography 

(PET). Blood oxygen level dependent MRI (BOLD) will identify hypoxic 

regions within prostate. Since this technique depends upon haemoglobin the 

predictive value is increased by combining BOLD sequences with dynamic 

contrast enhanced scanning to derive blood flow parameters. Combining the 

two will give a positive predictive value of over 85% for areas with a fast R2* 

signal representing hypoxia. Hypoxic regions may also be identified using 

PET with 18F-misonidazole. New hypoxic markers are under evaluation including 

64Cu-ATSM. Areas of increased proliferation and therefore potentially 

rapidly repopulating tumour may be identified using 18F-fluorothymidine 

labelled PET. By using a combination of functional imaging techniques it is 

therefore possible to identify tumour bearing areas of prostate which are hypoxic 

and other areas which are rapidly repopulating. Different treatment 

strategies may be chosen on the basis of these findings but dose escalation 

will form a fundamental component of this. Brachytherapy using high 

dose rate afterloading techniques offers the optimal means of dose escalation 

within subvolumes in the prostate gland. It avoids the difficulties of set-up and 

organ motion errors encountered with external beam radiotherapy and provides 

more flexible dose delivery than permanent seed implantation. Intrinsic 

dose heterogeneity in a brachytherapy treatment volume can be exploited by 

adjusting dwell times within each catheter. Hot spots of over 200% are readily 

achieved and can be targeted to the putative radioresistant areas defined on 

functional imaging. There are constraints in this approach primarily related to 

the dynamic nature of tumour physiology so that the gap between functional 

imaging and treatment delivery must be minimised. The radiobiological models 

for defining the extent of dose escalation are also exploratory at present 

and will need refinement and clinical evaluation. Summary Dose escalation 

for localised carcinoma of the prostate offers the optimal chance of tumour 

control. Targeting of dose to areas of increased tumour cell density, hypoxia 

and proliferation as defined on functional imaging can be best achieved by 

high dose rate afterloading brachytherapy. 

DNA damage repair and signaling responses: new 

developments and clinical potential 

4 speaker 

DNA DAMAGE REPAIR AND SIGNALING RESPONSES: NEW 

DEVELOPMENTS AND CLINICAL POTENTIAL 

R. Syljuasen 1 

1 INSTITUTE FOR CANCER RESEARCH, Department of Radiation Biology, 

Oslo, Norway 

A major cellular response to ionizing radiation is the induction of molecular 

signaling cascades. These signaling cascades control cellular processes 

such as DNA damage repair, cell cycle checkpoints and cell death pathways. 

Interestingly, many of the proteins involved in DNA damage signaling are 

products of genes that are frequently altered in human cancer. Thus, cancer 

cells often display differences in the DNA damage repair and signaling 

responses when compared to normal cells. Such differences between cancer 

and normal cells might be exploited in order to search for new strategies 

to selectively sensitize cancer cells to DNA damaging agents. Here, I will 

attempt to give a summary of our current knowledge of the DNA damage repair 

and signaling responses induced by ionizing radiation, with emphasis on 

the induced checkpoints. I will also discuss how such knowledge might be 

relevant for radiation therapy of cancer. 

PET and PET/CT technology for RT 

5 speaker 

PET AND PET/CT TECHNOLOGY FOR RADIATION THERAPY 

T. Beyer 1 

1 UNIVERSITÄTSKLINIKUM ESSEN, Essen, Germany 

Positron Emission Tomography is a functional imaging technique that yields 

3-dimensional, quantitative information of pre-selected metabolic pathways 

and activities in vivo. Depending on the choice of tracer molecules various 

metabolic pathways can be studied. As of today, 18F-labeled glucose has 

proven to be the workhorse in PET oncology imaging. FDG-PET yields a 

high sensitivity and specificity for a range of malignancies based on the fact 

that tumours are hypermetabolic and, therefore, can be differentiated from 

normal tissue based on an increased glucose metabolism.However, while 

FDG-PET has proven to be an efficient cancer staging modality a number 

of pitfalls and downsides remain. Several of these PET-associated disadvantages 

can be addressed by combining PET and CT within a single imaging 

device. Such PET/CT tomographs were first presented in 1998 and have 

S 5

S 6 TEACHING LECTURE MONDAY, SEPTEMBER 15, 2008 

been commercially available since 2001. Today, virtually no PET-only tomograph 

is produced for patient scanning anymore. Instead all PET systems 

come in combination with a CT. An increasing number of studies demonstrate 

the benefits of combined PET/CT imaging and furthermore substantiate the 

hypothesis of its improved diagnostic accuracy and clinical value. Through 

the intrinsic incorporation of CT technology PET/CT is an ideal tool for radiation 

therapy treatment planning. Several groups have started to investigate 

the efficacy of PET/CT-guided RTP. This talk will detail the following topics:- 

Combined PET/CT technology in the context of RTPo Design, performance, 

RT-based patient positioning, RT laser, DICOM connectivity- The usefulness 

of PET/CT in diagnosis and staging and subsequent treatment stratification- 

The efficacy and accuracy of PET/CT-based target volume delineationo BTV, 

GTV, patient motion and correction, inter observer variabilities, PET tracer- 

The use of PET/CT in therapy monitoring and restagingo Combined hardware 

and software fusion, therapy response criteria- New developments in 

PET/CT hard- and software specifically for RT planningo Hardware adaptations, 

image-based dosimetry planning for TRTWith the number of clinical 

PET/CT installations rising rapidly new requirements are being defined for 

efficient software utilities to help display, quantify and utilize the combined 

PET/CT information for diagnosis, therapy planning and follow-up and restaging. 

Just as PET/CT has become the modality of choice for oncology diagnosis 

it will become more prominent in radiation oncology. 

6 speaker 

LIMITATIONS OF STANDARD DOSIMETRY METHODS IN MODERN 

RADIOTHERAPY: FROM SMALL TO NOVEL BEAMS 

P. Andreo 1 

1 KAROLINSKA INST., University of Stockholm, Stockholm, Sweden 

Developments in radiotherapy techniques have substantially increased the 

use of small fields for stereotactic treatments, mostly with linacs, and larger 

uniform or non-uniform fields which are composed of small fields such as 

for IMRT. Standard-, mini- and micro- multi-leaf collimators (MLCs) have become 

almost standard equipment on conventional accelerators. At the same 

time there has been an increased use of treatment units specifically designed 

for stereotaxy (Gamma-Knife, Cyber-Knife) or intensity modulated treatments 

(Tomo-Therapy). These developments have gradually undermined clinical 

dosimetry, as the widely disseminated codes of practice for dosimetry, or 

dosimetry protocols, cannot be applied to the conditions under which these 

small or novel beams operate and no specific dosimetry recommendations 

have formally been developed. Users must then decide by themselves how to 

perform clinical dosimetry. Dosimetry errors have become considerably larger 

than in conventional beams mostly due to two reasons. First, even if the reference 

conditions recommended by codes of practice cannot be established 

in some machines, or treatment modalities be traced to them, dosimetry protocols 

are applied as if standard reference conditions would be valid. Second, 

even if relative dosimetry of small fields and composite fields appears to be 

conceptually simple, dosimetry issues mostly linked to the type of detector 

utilized have contributed to the problem. Such dosimetry errors usually affect 

the entire number of patients being treated with a specific modality. In order 

to develop standardized recommendations for dosimetry procedures and 

detectors, an international working party on Small and Novel Field Dosimetry 

has been established by the International Atomic Energy Agency (IAEA) 

in Cooperation with the AAPM Therapy Physics Committee. Other similar 

groups have been organized at national levels which are linked to the international 

working party. The presentation will outline the proposed methodology 

for the dosimetry of small single field and composite fields that will form the 

basis of new international recommendations. These will also address requirements 

for quality assurance and provide a standardized framework for 

establishing traceable dosimetry for the wide variety of beams and delivery 

techniques available. The contribution of the other working party members is 

gratefully acknowledged:R Alfonso, S Huq, W Kilby, R Mackie , A Meghzifene, 

R Capote, H Palmans, K Rosser, J Seuntjens, W Ullrich, S Vatnitsky. 

7 speaker 

ACUTE RADIATION THERAPY EFFECTS IN HEAD & NECK CANCER 

J. Giralt 1 

1 VALL D’HEBRON UNIVERSITY HOSPITAL, Department of Radiation 

Oncology, Barcelona, Spain 

Head and neck cancer (H&NC) is the fifth most common neoplasm worldwide, 

the estimated incidence being more than 500,000 cases diagnosed per year. 

Their anatomic situation means that treatment can affect vital functions, such 

as speech or swallowing, that may considerately reduce a patient’s quality of 

life. The management of advanced cancer of H&NC involves the sequential 

or simultaneous use of several treatment options, including surgery, radiotherapy, 

and chemotherapy. Concurrent chemotherapy and radiotherapy (CT- 

RT) has become the standard of care for the treatment of locally advanced 

H&NC. As we have become more aggressive with CT-RT, toxicity rates have 

increased as well. Furthermore, time compression of dose delivery in accelerated 

fractionation has produced also high rates of severe toxicity. Oral 

mucositis is one of the most debilitating side effects of radiation therapy in the 

treatment of H&NC. Severe mucositis causes substantial pain, interferes with 

the patient’s ability to chew and swallow, and worsens the patient’s quality of 

life (QoL). It is the dose-limiting toxicity of treatment modalities like accelerated 

fractionation and CT-RT and the cause of treatment interruptions. Management 

of mucositis may require feeding tube placement, hospitalization, 

pain control using patient-controlled morphine and intensive supportive care. 

Radiation dermatitis is observed in most of the patients, being severe in 20- 

25% of cases. Its onset varies depending on the total skin dose, the dose per 

fraction, the overall treatment time, beam type and energy, and the surface 

area of the skin that is exposed to radiation. Severe reactions cause local discomfort, 

affecting patients’ QoL, and may lead to unplanned treatment delays. 

The effect on the skin of EGFR inhibitors plus radiation is of considerable interest, 

as it might require special care to reduce symptoms and severity. Considering 

the fact that radiation is known to upregulate EGFR, it would appear 

possible that there is some biological interplay between the pathophysiological 

effects of radiation on the skin and those of EGFR inhibitors. Xerostomia 

is one of the most common complications during and after radiotherapy for 

H&NC, because irreparable damage is caused to the salivary glands, which 

are included in the radiation fields. Xerostomia not only significantly impairs 

the QoL of potentially cured cancer patients, it may also lead to severe and 

long-term oral disorders. Various strategies have been used in recent years 

to reduce xerostomia after irradiation of H&NC, including radiation protectors, 

salivary stimulants, surgical transfer of a submandibular salivary gland away 

from the radiation fields, and IMRT aimed at the sparing of the parotid salivary 

glands. This overall increase in toxicity also points to a need to optimize therapeutic 

combinations. Among the possible ways to improve the therapeutic 

ratio, IMRT could be useful in preserving the parotid function and in reducing 

toxicity by sparing swallowing structures.

MONDAY, SEPTEMBER 15, 2008 SYMPOSIUM 

Symposium 

BIOCARE 

8 speaker 

OVERVIEW OF BIOCARE 

A. Brahme 1 

1 KAROLINSKA INSTITUTET, Medical Radiation Physics, Stockholm, Sweden 

BioCare is aimed at developing molecular tumor imaging for biologically optimized 

cancer therapy and cover a broad range of activities from the development 

of better diagnostic PET-CT equipment, improved diagnostic tracers, 

PET-CT based therapy optimization, PET-CT simulation and clinical validation 

of new tracers for tumor therapy response imaging. Here only one interesting 

example will be discussed, where the collaborating efforts of several work 

packages during the last few years have resulted in an continued improved 

understanding of the response of severely radiation resistant hypoxic tumours 

and new methods to achieve augmented therapeutic results. These tumours 

have a poorly functioning peripheral vasculature which may be visible with 

vascular tracers and FDG. The core of such tumours has a very poor vascular 

flow, which is insufficient for oxygenation and FDG uptake studies as 

seen by PET-CT, Doppler ultrasound or MRI. Today we understand that these 

hypoxic cores generally are due to a high interstitial tumour pressure which 

often is caused by a high Platelet Derived Growth Factor (PDGF) expression 

or for lung tumors also by a high pressure of the venous blood reaching the 

tumor directly from the heart. This latter mechanism has recently been observed 

clinically using the latest generation of PET-CT scanners with a 64 

slice CT detector. Their rapid imaging allow efficient freezing of the motion of 

the vasculature of the lung during breathing and visualization of the large vessels 

coming from the heart and directly reaching the periphery of the tumor. 

The high pressure of the blood in these vessels may close off the internal 

blood flow of the tumor, similar to what would happen in the brain in absence 

of the dura mater which prevents collapse of exiting vasculature and thus a 

reduction of the blood flow. When treated by radiation the FDG uptake slowly 

increases due to a better vascularisation as tumour cells in the core are increasingly 

eradicated and reducing the internal pressure. However, the initial 

hypoxia means that almost 3 times the dose needs to be delivered compared 

to a well oxygenated tumor. Generally the surrounding normal tissues will 

not tolerate so massive doses so these tumours are often recurrent. Different 

ways to improve vascularisation by PDGF antagonists like Glivec, antiangiogenic 

drugs like Avastin and hyperbaric oxygen may be used trying to improve 

the therapeutic outcome by increasing the vasculature before starting 

the treatment. In this way the therapeutic effect is increased in the tumor and 

significantly doses are needed for curation. 

9 speaker 

IMAGE-GUIDED DOSE ESCALATION IN RECTAL CANCER 

S. Roels 1 , P. Slagmolen 2 , J. Nuyts 3 , S. Stroobants 3 , N. Ectors 4 , F. 

Penninckx 5 , K. Haustermans 1 

1 UNIVERSITY HOSPITAL LEUVEN, Radiation Oncology, Leuven, Belgium 

2 UNIVERSITY HOSPITAL LEUVEN, Medical Image Computing (ESAT/PSI), 

Faculties of Medicine and Engineering, Leuven, Belgium 

3 UNIVERSITY HOSPITAL LEUVEN, Nuclear Medicine, Leuven, Belgium 

4 UNIVERSITY HOSPITAL LEUVEN, Pathology, Leuven, Belgium 

5 UNIVERSITY HOSPITAL LEUVEN, Abdominal Surgery, Leuven, Belgium 

Purpose Rectal cancer patients at high risk for local recurrence could benefit 

from radiotherapy (RT) dose escalation to the primary tumour. Accurate dose 

delivery requires an accurate definition and delineation of the tumour. The 

purpose of this study was to investigate the use of [18F]fluorodeoxyglucose 

(FDG) PETCT and magnetic resonance imaging (MRI) for RT target definition 

in rectal cancer. Additionally, the spatial distribution between FDG-PETdefined 

and MR-defined tumour volumes and their quantitative and spatial 

evolution during RT was assessed. Patients & Methods In 15 patients with resectable 

rectal cancer, FDG PETCT and MR were performed before, after 10 

fractions of RT and at the time of surgery. FDG-PET signals were automatically 

segmented with different delineation methods: an adaptive threshold 

method determined on the basis of the signal to background ratio (SBR) and 

a gradient-based segmentation method (GR). MR T1-weighted images were 

used for manual tumour delineation by an experienced radiologist. To register 

the different images, we applied a non-rigid image registration algorithm using 

a B-spline transformation model and mutual information constraints without 

use of regularisation penalties. Mismatch analyses were carried out to 

quantify the resulting overlap between the different volumes. The applied delineation 

methods on MR and PET were validated by comparing the preoperative 

images to the pathological tumour volume. Results Forty-five sequential 

PETCT and MR images were analyzed from 15 patients. On average, both 

MR and FDG-PET showed a trend towards tumour shrinkage during and after 

CRT. The mean MR volume was larger compared to the FDG-PET volume 

(Figure). The mean mismatch between FDG-PET and MR, calculated as the 

fraction of the PET volume that projects outside the MR, was 38% (range: 

7%-89%) and 35% (5%-88%) during RT. After 10 fractions of RT, 61% of the 

FDG volume remained inside the contour of the baseline FDG volume (range 

0%-94%). A similar result (59% (6%-95%)) was seen for the registration of 

the FDG volume obtained after RT to the baseline volume. On MR, 69% 

(21%-91%) of the MR volume during RT and 65% (0%-97%) of the MR volume 

after RT overlapped with the baseline volume. In 3/6 patients with a 

pathological complete tumour remission (pCR), there was a metabolic complete 

response on FDG-PET, whereas on MR, residual tumour tissue was 

still suspected in all 6 pCR patients. Conclusion Integration of more detailed 

anatomical MR images and additional FDG-PET information into the conventional 

CT-based RT planning seems feasible, provided that accurate registration 

and delineation algorithms are used. Spatial variance between MR 

and PET volumes should be taken into account in defining the target volume. 

Re-imaging during treatment can detect changes in geometry and functional 

characteristics/metabolism of the tumour, which support its use for adaptive 

RT. 

10 speaker 

PET-TRACER FOR RADIOTHERAPY RESPONSE: PRECLINICAL 

INVESTIGATIONS 

B. Beuthien-Baumann 1 , R. Bergmann 2 , V. Grégoire 3 , K. Haustermans 4 

1 

UNIVERSITÄTSKLINIKUM TECHNISCHE UNIVERSITÄT DRESDEN, Klinik für 

Nuklearmedizin, Dresden, Germany 

2 

FORSCHUNGSZENTRUM DRESDEN-ROSSENDORF, Institut für Radiopharmazie, 


3 

UNIVERSITÉ CATHOLIQUE DE LOUVAIN, Department of Radiation Oncology, 


4 

UNIVERSITAIR ZIEKENHUIS GASTHUISBERG, Radiation Oncology, Leuven, 

Belgium 

Positron Emission Tomography (PET), widely accepted for staging in oncology, 

is increasingly used for therapy response assessment. The objectives 

of workpackage 3 of the EU-project Biocare were the investigation of PET 

imaging for monitoring of therapy responses in small animal tumour models. 

This WP combined the investigation of PET scanning with information 

from autoradiography, functional histology and functional assays, aiming at 

a deeper insight into tumour biology, identification of the histological basis 

of the macroscopic PET signal under therapeutic conditions and identification 

of sensible tracers for tumour response monitoring.A panel of tumour 

xenografts on mice (SCC, adenocarcinoma, fibrosarcoma) were investigated 

with dedicated small animal PET. PET tracers investigated covered glucose 

metabolism (18F-FDG), proliferation (18F-FLT), and hypoxia (i.e.18F-Miso). 

PET was correlated to functional histology (i.e. pimonidazole, Glut1, Ki- 

67) and autoradiography. Treatment regimen included single dose irradiation 

(SD) and the COX2-inhibitor celecoxib. End points of treatment experiments 

were local tumour control or tumour growth delay.It was observed, that in 

different tumour entities the FDG-distribution at microscopic level may vary 

considerably concerning the relation to hypoxia and proliferation: While in the 

hSCC FaDu FDG-uptake was higher in hypoxic and Ki-67-positive tumour areas 

respectively, this was not observed in the h-adeno-ca HT29. After SD 

S 7

S 8 SYMPOSIUM MONDAY, SEPTEMBER 15, 2008 

irradiation most of the tumours investigated showed at the macroscopic PET 

level a decrease of FDG-uptake during follow up. FTL declined at day 1, but 

was back to base line 1 week post SD in HCT116. In HCT116, after COX2inhibitor 

FDG-uptake and FDG-pos. volume was stable, while FLT showed 

an increase of uptake but a decrease in FLT-pos. volume.Prognostic information 

(SD-experiments): An increase of radiation dose had a greater effect on 

local control in FaDu tumours with high pretherapeutic FDG-uptake than in 

tumours with low FDG-uptake. With 18F-Miso and FaDu, not the intensity of 

the PET signal but the 18F-Miso-positive volume was important: the smaller 

the hypoxic tumour volume, the better the chance of permanent local tumour 

control. Comparing tracer distribution in matching tumour slices from FDG- 

PET and autoradiography, image segmentation revealed local discrepancies 

of tracer distribution. Conclusion: PET-imaging is able to monitor treatment 

response in different tumour models and may offer prognostic information. 

Profound biologic information is gained by combining PET with autoradiography 

and histology. Possible local discrepancies in PET tracer distribution on 

PET- and autoradiography level have to be explored further with regard to clinical 

application. This work was supported by the 6th framework EU-project 

"BioCare", proposal #505785 

11 speaker 

BIOCARE - PET IMAGING FOR MONITORING OF TREATMENT IN 

MAN 

A. Saleem 1 

1 CHRISTIE HOSPITAL NHS FOUNDATION TRUST, Academic Radiation 

Oncology, Manchester, United Kingdom 

The role of positron emission tomography (PET) imaging for monitoring of 

anti-cancer therapy in man was evaluated as part of the ’Molecular imaging 

for Biological optimised cancer therapy’ (BioCare) project. The objectives 

were to develop and validate PET techniques for monitoring of anti-cancer 

therapy and its application. Clinical studies were conducted in a number of 

participating centres throughout Europe. Validation studies were carried out 

with [15O]-water (blood flow), [18F]-fluorothymidine (FLT) (proliferation), and 

[18F]-fluoromisonidazole (FMISO) (hypoxia) in a variety of tumours. Studies 

with [15O]-water also evaluated the validity of using an image derived 

input function instead of arterial input function for perfusion modelling in the 

imaging of abdominal tumours and the effect of injected dose of [15O]-H2O 

on the statistical quality of PET image data and accuracy. Validation studies 

correlating FMISO with pimonidazole immunohistochemistry in head and 

neck cancers have been completed. Work was carried out evaluating a 

number of algorithms for non-rigid registration in adaptive radiation therapy 

for the treatment of head and neck cancers, from which an optimal algorithm 

was selected. PET was used to monitor radiotherapy, chemotherapy 

or biological treatments in a variety of cancer types including non-small lung 

cancer (NSCLC), pharyngo-laryngeal cancer, soft tissue sarcoma, mesothelioma, 

pancreatic cancer and soft tissue sarcoma. Results from these studies 

have shown that FLT-PET in patients with head and neck cancer undergoing 

radiotherapy did not discriminate between reactive and metastatic lymph 

nodes. With [18F]fluorodeoxyglucose (FDG)-PET there was a significant impact 

on delineation of target volumes and dose-distribution during adaptive 

radiotherapy in patients with pharyngo-laryngeal tumours. In patients with 

NSCLC, monitoring of FDG uptake during a course of fractionated radiotherapy 

demonstrated that FDG uptake showed large intra-individual heterogeneity 

and different time trends were observed for metabolic responders compared 

to non-responders. Evaluation of tumour blood flow with radiolabelled 

water was also carried out in patients taking part in a dose-escalating phase I 

study of a vascular disrupting agent to determine the optimal biological dose. 

Overall, the aims of the project were generally achieved and a number of 

presentations and publications have resulted from work carried out. 

Interdisciplinary treatment of locally advanced 

prostate cancer 

12 speaker 

DEFINITIVE RADIOTHERAPY FOR LOCALLY ADVANCED 

PROSTATE CANCER 

M. Bolla 1 , F. Philippe 1 , V. Camille 1 

1 CHU DE GRENOBLE - A.MICHALLON, Department of Radiation Oncology, 

Grenoble, France 

External beam irradiation is the treatment of choice of locally advanced 

prostate cancer, T2c T3-4 N0-X M0 (TNM UICC 2002) provided it is combined 

with androgen suppression. The challenge is : i) to decrease the volume of 

the prostate ii) to improve the effectiveness of radiation by increasing its apoptotic 

effect iii) to decrease the occurrence of distant metastases due to infraclinical 

deposits at the time of diagnosis. The main trials showing a survival 

benefit were launched by the Radiation Therapy Oncology Group (RTOG) and 

the European Organisation on Treatment and Research on Cancer (EORTC), 

all using an LHRH analogue. According to Gleason score and modalities of 

administration a significant improvement in overall survival has been shown 

: i) for patients with poorly-differentiated tumours with either LHRH analogue 

being prescribed alone the last week of irradiation and continued until relapse 

(RTOG trial 85-31), or CAB given before and during irrradiation and followed 

by 2 years of LHRH analogue (RTOG Trial 92-02) . ii) for patients with Gleason 

score 2-6 with a CAB prescribed 2 months before and during radiation 

therapy (RTOG trial 86-10). iii) whatever the histological grade with LHRH 

analogue administered during and after irradiation for a total duration of 3 

years (EORTC trial 22863). Within the frame of an equivalence trial, EORTC 

trial 22961 has definitely shown that a long term androgen deprivation (3 

years ) is better than a short one (6 months). Innovative techniques such as 

three dimensional conformal /intensity modulated external beam radiotherapy 

might contribute to improve the results with dose escalation. 

13 speaker 

SURGERY ALONE FOR LOCALLY ADVANCED PROSTATE CANCER 

M. Wirth 1 

1 UNIVERSITY HOSPITAL CARL GUSTAV CARUS DRESDEN, Department of 

Urology, Dresden, Germany 

The term "locally advanced prostate cancer" is used for a wide spectrum of 

patients. Patients with lymph node metastases, true clinically non-organ confined 

tumors as well as patients with overstaged localized and thus curable 

prostate cancer may fall into this category. The treatment of locally advanced 

prostate cancer is subject to controversies. Radical prostatectomy, external 

beam radiotherapy and early or deferred hormonal therapy are possible treatment 

options. Frequently, several modalities are combined (multimodal treatment). 

Up to now, no advantage for the tantalizing strategy of downstaging 

or downsizing by neoadjuvant hormonal therapy has been demonstrated convincingly. 

After radical prostatectomy, similar grade-adjusted disease-specific 

survival may be achieved as in histopathologically localized disease. Exact 

staging and sparing adjuvant treatment to true high risk patients and the 

preservation of the option of curative radiotherapy are advantages for radical 

prostatectomy in locally advanced prostate cancer. After failure of external 

beam radiotherapy, on the other hand, radical prostatectomy is technically 

challenging and accompanied by an increased risk of complications. In 

patients with histopathological prove of locally advanced disease or positive 

margins, adjuvant radiotherapy may beneficial in terms of biochemical and 

local control; a survival advantage has, however, not yet been demonstrated. 

In the case of lymph node metastases after radical prostatectomy, but not in 

node-negative locally advanced disease, adjuvant hormonal treatment may 

improve survival. 

14 speaker 

ADJUVANT RT AND RT FOR PSA ELEVATION AFTER RADICAL 

PROSTATECTOMY 

T. Wiegel 1 

1 UNIV.- KLINIK ULM, Department of Radiation Oncology, Ulm, Germany 


Shaping the RT future: clinical and technology 

15 speaker 

ROLE OF GENOMICS AND PREDICTION OF RESPONSE 

A. Begg 1 

1 NETHERLANDS CANCER INSTITUTE, Department of Experimental Therapy, 

Amsterdam, Netherlands 

Purpose: To review current data on the value of genomics for predicting 

outcome where radiotherapy is the primary treatment modality, and to summarize 

future trends and possibilities. 

Methods: A literature review of genome wide profiling at the DNA and RNA 

levels will be given. This will include studies on array comparative genomic 

hybridization (aCGH), epigenetic changes, messenger RNA (mRNA) and microRNA 

(miRNA) profiling. In addition, data generated in our own lab on 

mRNA profiling of head and neck tumors treated with either radiotherapy 

alone or radiotherapy combined with cisplatin will be presented. 

Results: Expression profiling of mRNA in tumor biopsy material has shown 

promise in a variety of studies for predicting outcome, including local control 

and survival. Some expression signatures distinguish good and poor prognosis 

patients in a variety of tumors given a variety of treatments. These assess 

general malignancy. Few signatures to date have shown specificity for a particular 

treatment type, which are inherently more useful. Signatures for several 

biological processes and phenotypes, e.g. hypoxia, wounds, chemosen-


sitivity and radiosensitivity, have been defined on cell lines in culture. Several 

of these have surprisingly good predictive potential in clinical series. aCGH 

has also shown prognostic value in several studies, although signatures specific 

for radiation are lacking so far. Combining aCGH with expression profiling 

has demonstrated its value in distinguishing relevant from irrelevant genetic 

changes. Finally, microRNAs have been shown to play important roles in 

tumor development and in response to treatment. miRNA profiling is fundamentally 

different from mRNA profiling and should provide complementary 

and potentially powerful predictive information. 

Conclusions: The distinction between prognostic and predictive signatures 

is important for all genome wide studies. Hardly any treatment specific (predictive) 

signatures have been reported to date (although many prognostic 

signatures exist), and these are necessary for both increased understanding 

of treatment response and for the design of more rational interventions. The 

combination of genome wide techniques holds promise for improving prediction 

in the future. 

16 speaker 

TARGETED THERAPIES AND THE POTENTIAL FOR INDIVIDUAL- 

IZATION OF TREATMENT 

G. McKenna 1 

1 CHURCHILL HOSPITAL, Oxford, United Kingdom 


17 speaker 

WHAT’S AFTER IGRT? 

C. Ling 1 

1 MEMORIAL SLOAN-KETTERING CANCER CTR, New York, USA 


18 speaker 

FUTURE CLINICAL TRIAL DESIGN AND THE USE OF BIOLOGIC 

ENDPOINTS AND AGENTS IN RADIATION ONCOLOGY 

R. Corvo 1 

1 NATIONAL CANCER RESEARCH INSTITUTE AND UNIVERSITY, Radiation 

Oncology, Genoa, Italy 

The combination of novel biological targeted-therapies with radio(chemo)therapy 

is a rapidly expanding area of research. Novel 

biological therapies include: 1. agents that target growth factor receptor 

pathways; 2. therapies that target anti-growth factor evasion; 3. drugs 

that are able to either reactivate cell death signals or inactivate survival 

signals; 4. agents able to switch signalling on or off, respectively through 

the pro-angiogenic or anti-angiogenic pathways; 5. vectors for the delivery 

of therapeutic genes that can only be expressed in cancer cells showing 

immortalisation by reactivation of telomerase. This molecular scenario offers 

the prospect of designing smart tumor-directed therapies that exert preferential 

mechanististically favourable effects to yield additive, synergistic or even 

independent anti-cancer actions when combined with radio(chemo)therapy. 

In this context, a critical point is the possibility that novel targeted drugs 

may increase normal tissue toxicity or antagonise anti-tumor efficacy of 

the standard therapies. Preclinical data should be able to define suitable 

groups of patients for clinical trials on the basis of the underlying cancer 

biology. Phase I trials should give more useful informations on therapeutic 

effects than conventional Phase I trials. These trials should be conducted in 

patients with specific tumor types and the goal should include identification 

of the optimal biological dose (OBD) of the explored agent to be used 

with radio(chemo)therapy rather than the maximum tolerated dose. The 

OBD is defined as the lowest dose level showing optimal biological activity 

and no-dose limiting toxicity. Establishing a OBD for a biological agent is 

difficult because these agents are generally cytostatic in nature, making 

tumor skrinkage in a clinical trial an insensitive measure of efficacy. These 

findings point to the need for biological end-points to serve as early surrogate 

measures of benefit and development of treatment resistance. The use of 

biological end-points (i.e. tumor biopsy material, circulating factors, functional 

imaging measuring by PET/MR changes in the tumor after therapy) is still 

under investigation for objective assessment of their relevance. Subsequent 

Phase II trials should have a randomised design in order to allow clinicians 

to obtain an initial evidence of the efficacy of the new combination in 

comparison with standard therapy. Phase III trials might evolve to require 

smaller numbers of patients with tumors that are biologically homogeneous 

in which testing of new associations represents a rational strategy. In the 

absence of validated surrogate biomarkers for patient selection a reasonable 

approach for combining biological agents with radio(chemo)therapy may be 

to focus on tumor entities in which local control is sub-optimal. In addition, 

tumors for which novel agents have produced superior survival in the 

treatment of advanced radio(chemo)resistant disease would be also logical 

candidates. However, advances in biomarker development in clinical trials of 

targeted-therapy with radio(chemo)therapy should be a priority, particularly 

as the high cost of such biological agents may result in a major burden for 

health care systems. 

New radiobiology insights applicable to 

brachytherapy 

19 speaker 

CAN RADIOBIOLOGY PROVIDE RELIABLE ESTIMATES OF ADDING 

DOSES FROM IMAGE GUIDED EB 

S. Bentzen 1 

1 UNIV. OF WISCONSIN SCHOOL OF MEDICINE AND PUBLIC H, Madison WI, 

USA 


20 speaker 

IS THE LQ MODEL APPLICABLE FOR BRACHYTHERAPY WITH 

LARGE DOSES PER FRACTION? 

M. Joiner 1 

1 WAYNE STATE UNIVERSITY / KARMANOS CANCER, Department of 

Radiation Oncology, Grosse Pointe, USA 

Background: The Linear-Quadratic (LQ) model describes cellular responses 

to ionizing radiation very well at doses less than ~6 Gy and is the preferred 

model to use in this dose range. However at higher doses, in vivo assays 

show that the response of cells more closely resembles a linear relationship 

between ln(Surviving Fraction) and dose. Therefore models derived from target 

theory may better describe tissue responses to high doses per fraction 

used in brachytherapy.Methods: The two-component (TC) model has the correct 

behavior for large fraction sizes. Therefore, for a given α/β ratio, parameters 

in the TC model were derived that (1) lead to close agreement with 

tolerance doses predicted by the LQ model for doses per fraction 1-5 Gy, and 

(2) lead to high-dose D0s that agree with those observed from in vivo colony 

assays. For long individual treatment sessions, the incomplete-repair model 

was used to estimate loss of effectiveness.Results: High-dose D0s determined 

for a variety of tissues lie in the range 1.3-1.7 Gy. For a given α/β ratio 

and D0 = 1.5 Gy, unique parameter triples of the TC model are determined. 

Changes in doses per fraction in the high range 10-25 Gy lead to tolerance 

doses predicted by the TC model that are (1) higher and (2) less variable than 

those predicted by the LQ model. Corrections for protracted treatment time 

are in the 5-8% range.Conclusions: With large doses per fraction, the TC 

model may more accurately describe the responses to brachytherapy. Using 

the LQ model to predict high-dose responses from responses in the lower 

dose range, may overestimate the effect on the tumor and underestimate 

normal tissue tolerance. 

21 speaker 

QUANTIFYING EFFECTS OF DOSE INHOMOGENEITIES AND 

VARIATIONS IN DOSE RATE 

C. Armpilia 1 

1 ARETEION HOSPITAL, Athens, Greece 

The aim of this lecture is to review radiobiological quantification of i) dose-rate 

effects and ii) dose-gradient effects in brachytherapy applications.Dose-rate 

effects arise from the fact that sub-lethal damaged cells have the propensity 

to repair when dose delivery time is protracted (i.e. dose rate is lowered). 

Repair rates and α/β ratios are the main parameters which influence tissue 

responses when dose-rate is changed. Radiobiological equations, using 

extended version of the linear-quadratic model which quantify the dose-rate 

effect are presented for the main types of brachytherapy applications, i.e. 

high dose rate (HDR), low dose rate (LDR), pulsed (PB) and permanent interstitial. 

Brachytherapy dose distributions are strongly influenced by high 

dose gradients which are present. The dose gradients arise largely from the 

inverse-square effect and inevitably mean that both dose and dose rate vary 

throughout the treatment volume. This has important biological implications, 

i.e. when calculating the Biologically Effective Dose (BED as specified within 

the LQ model). Methods for incorporating dose gradient effects in order to 

determine an ’equivalent’ BED (BEDeq) within non-uniformly irradiated tissues 

are discussed. The BEDeq in a brachytherapy application corresponds 

to that associated with the uniform dose which would have to be applied to 

the same volume to yield the same surviving cells as does the brachytherapy. 

The concept is analogous that of the Equivalent Uniform Dose (EUD) for nonuniform 

external beam therapy. Allowance of dose-gradient effects has a role 

S 9


to play in the prospective design of safe radiation schedules as well as in the 

retrospective analysis of past treatments. 

Cancer stem cells and impact for clinical radiotherapy 

22 speaker 

HYPOXIA AND CANCER STEM CELLS AND METASTASIS 

R. P. Hill 1 

1 ONTARIO CANCER INSTITUTE/PRINCESS MARGARET HOSPITAL, Toronto, 

Ontario, Canada 

Hypoxia in tumours has been associated with more aggressive disease and 

increased metastatic spread in a variety of tumour types. Mechanisms underlying 

these observations remain uncertain although there is strong evidence 

that changes in the expression of metastasis-related genes may play a critical 

role, even though different genes are likely involved in different cancers. An 

important aspect of hypoxia in tumours is that it can occur both for prolonged 

time periods (chronic or diffusion-limited hypoxia) or as a result of intermittent 

changes in blood flow or red cell flux in individual blood vessels (acute or perfusion 

limited hypoxia). Our studies in vitro with a human cervical carcinoma 

cell line (ME180) have demonstrated that many metastasis-related genes are 

upregulated following exposure to chronic and acute hypoxia. Many of these 

same genes are also upregulated in orthotopic xenografts of the ME180 cells, 

in particular in the hypoxic cells in the tumour and in their lymph node metastases. 

Interestingly exposure of the tumour-bearing animals to acute (cyclic) 

hypoxia during their growth enhances lymphatic metastases. We are currently 

studying whether blocking the activity of some of these genes (e.g 

CXCR4, VEGF-C) may prevent this increase in metastases. Since, by definition 

metastases must arise from cancer stem-like cells it is also of interest 

to ask whether such cells exist in hypoxic regions of tumours and express 

such genes. To date relatively little information is available concerning this 

issue, however, there is some evidence that certain normal tissue stem cells 

may reside preferentially in an hypoxic niche, suggesting the possibility that 

this may also be the case in certain tumours. Further studies are needed to 

address this issue. 

23 speaker 

CHARACTERIZATION OF RADIATION RESISTANT STEM CELL 

PHENOTYPES IN HUMAN BREAST CANCER 

W. Woodward 1 , W. XU 2 , B. Debeb 2 , L. Li 2 , H. Mok 1 

1 

U.T. M.D. ANDERSON CANCER CENTER, Radiation Oncology, Houston, 

TX, USA 

2 

U.T. M.D. ANDERSON CANCER CENTER, Department of Experimental 

Radiation Oncology, Houston, TX, USA 

It has been suggested that breast progenitor cells, normal and malignant may 

be resistant to radiation, and that this may be mediated by stem cell survival 

pathways such as Notch and Wnt/beta-catenin. Targeting of survival 

pathways is an attractive therapeutic option if these cells are truly radioresistant, 

and if a meaningful therapeutic window between normal and cancer 

stem cells exists. Data from human breast cancer cell lines assessing enrichment 

for stem/progenitor cell phenotypes after radiation will be reviewed. 

Challenges in correlating short end-point marker studies to clonogenic assays 

will be discussed, and clonogenic assays comparing three-dimensional 

non-adherent progenitor promoting cultures to standard clonogenic assays 

presented. In an IRB approved study metastatic breast cancer cells were 

obtained in suspension after patients underwent therapeutic thoracentesis. 

Cancer stem/progenitor cells were assayed for stem progenitor phenotypes, 

cultured in non-adherent 3-D culture and subjected to ex vivo radiation. Enrichment 

in stem/progenitor cell phenotypes is evident after radiation in clinical 

samples. Issues related to translating these studies into primary material 

and multi-institutional trials will be discussed. 

24 speaker 

EVIDENCE FOR DISSOCIATION OF RESPONSE OF CANCER 

STEM CELLS AND NON-TUMOURIGENIC CELLS IN RADIATION 

ONCOLOGY 

M. Baumann 1 

1 UNIVERSITY OF TECHNOLOGY, MED. FAC. CARL GUSTAV CARUS, 

Department of Radiation Oncology, Dresden, Germany 

The aim of curative radiotherapy is to achieve permanent local tumour control. 

Recurrent tumours after radiotherapy originate by definition from at least 

one surviving cancer stem cell while permanent local tumour control requires 

inactivation of all cancer stem cells. This neglects the possibility that some 

tumors may be cured even if few stem cells survive the immediate effects of 

therapy, e.g. by tumour bed effects. Recent experimental techniques which 

combine isolation of tumour cell population based on specific surface markers 

with transplantation assays support that cancer stem cells are a specific 

subpopulation of all cancer cells, while the vast majority of cancer cells are 

non-tumourigenic. The question whether cancer stem cells may respond differently 

to radiotherapy or combined modality treatment compared to the bulk 

of non-stem tumour cells is of considerable scientific and practical interest. 

Changes in tumour volume after therapy, i.e. tumour response, are governed 

by the changes in the mass of tumour cells, i.e. primarily by the non-stem 

cells. In contrast, permanent tumour eradication is solely dependent on the 

complete inactivation of the subpopulation of cancer stem cells. Today the 

vast majority of preclinical studies in cancer research use volume dependent 

parameters such as tumour regression or tumour growth delay as experimental 

endpoints. This carries the substantial risk that new treatments may 

be optimized for their effect on the bulk of non-stem cancer cells, with no 

improvement in the curative potential. An overview will be given on recent experiments 

showing dissociation of tumour volume dependent endpoints and 

tumour cure after combined modality treatments and on experiments which 

attempt to directly measure the radiosensitivity of cancer stem cells. 

Biological target volumes and dose painting 

25 speaker 

EMPIRICAL APPROACH OF DOSE PAINTING 

W. De Neve 1 , I. Madani 1 

1 UZ GENT, Radiotherapy, Gent, Belgium 

In their editorial [1] entitled "Dose painting: Art or Science", Tanderup, 

Olsen and Grau discuss the vision behind dose painting based on biological 

imaging techniques. The authors argue that clinical implementation of 

dose painting should await a number of investigations including i) the 

clinical and biological rationale of inhomogeneous dose prescriptions; ii) 

preclinical evaluation using animal models; 3D-investigations on tumor 

regression during radiation therapy and iv) 3D-assessment of patterns of 

relapse; v) monitoring the changes of radiobiological parameters over time 

vi) developing methodology to incorporate time dependence in the treatment 

planning and vi) developing and assessing tools for plan evaluation and 

plan comparison. I agree that pre-clinical investigations could address the 

numerous unanswered questions on dose painting including those regarding 

the transformation of signal intensity to desired dose and fractionation for 

plan optimization engines. If we call knowledge-delayed, the approach that 

aims at funding the biological and biophysics basis first for clinical dose 

painting later then I would call empirical-now the approach of immediately 

conducting clinical trials without having the scientific knowledge for most 

of the issues raised in the abovementioned editorials. Yet I disagree with 

the editorials that clinical implementation should be delayed until it can 

be knowledge-based. Safe phase I-III trials with potential benefit to the 

patient can be undertaken with limited knowledge; actually no more than a 

solid hypothesis regarding the qualitative relationship between image signal 

intensity and radioresistance is required. A positive relationship -more signal 

intensity reflects more radioresistance- would guide to positive dose painting 

with dose intensification to regions of more intense signal, a negative 

relationship to negative dose painting. In the empirical-now approach, phase 

I trials need to answer questions related to dose/volume/toxicity i.e. how 

much dose intensification is possible to which sub-volumes of the tumor 

without reaching dose-limiting toxicity and allow correlating the patterns of 

relapse with dose-intensification [2]. Subsequent Phase II trials need to 

answer questions of anti-tumor activity and should best be conducted in 

a randomized design against standard homogeneous irradiation. Phase 

III trials should answer questions regarding efficacy in a multi-institutional 

setting and generate evidence for the replacement of the actual standard 

radiotherapy by dose painting. None of these questions can be answered 

by pre-clinical research. A proper trial design is required to account for time 

dependence of signal intensity and distribution. Tools for plan evaluation and 

plan comparison using a score of deviations between dose objectives for 

planning and dose prescription have been described [3]. I strongly argue 

to conduct empirical-now clinical trials simultaneously with translational 

and fundamental research. By doing so, the clinical trials might prevent 

derailing of the pre-clinical work into irrelevant directions. A simultaneous 

approach is the best guarantee for generating the basic data for replacing 

empirical transformations by solid biological models and might guide clinical 

trial design. In conclusion: empirical clinical trials of dose painting are 

essential while pre-clinical work might provide the knowledge-basis for new 

hypotheses that enhance the rate of progress. 

References: 

1. Tanderup K, et al. Radiother Oncol. 2006 Jun;79(3):245-8 

2. Madani I, et al. Int J Radiat Oncol Biol Phys. 2007 May 1;68(1):126-35 

3. Vanderstraeten B, et al. Radiother Oncol. 2006 Jun;79(3):249-58


26 speaker 

METHODS AND TECHNOLOGY FOR THE APPLICATION TO HEAD 

AND NECK TUMOURS 

M. Alber 1 

1 UNIVERSITÄTSKLINIK FÜR RADIOONKOLOGIE, Tübingen, Germany 

Functional imaging for target definition of head and neck tumours comprises a 

multitude of methods, with various MR techniques and PET tracers to visualize 

a wide range of biological and physiological properties of the tumour. The 

emerging preferred method for tumour delineation is FDG-PET while other 

tracers have been employed to visualize hypoxia, proliferation or neovascularization. 

MR methods have been applied to image perfusion, blood oxygen 

content, or diffusion. In general, it is difficult to establish a relationship 

between the image information and radiobiologically meaningful properties 

which could be used to modify radiotherapy. The first step is always an understanding 

of the physical limitations of the image such as misregistration, 

resolution, blurring and artefacts. Computer algorithms to deal with these 

problems have been shown to improve the quality of tumour delineation. In 

a second step, functional images can be used for patient selection for indiscriminate 

dose escalation, or ideally for a spatially resolved differential dose 

prescription aka dose painting. While this has been shown to be technically 

feasible with IMRT or IMPT, the required dose levels to produce a relevant effect 

in a population are still unclear. A method to derive these from a patient 

data set of hypoxia-sensitive PET imaging and follow-up data is presented. 

27 speaker 

DOSE PAINTING FOR BIOLOGICAL INDIVIDUALIZATION OF 

RADIOTHERAPY 

C. Chao 1 

1 U.T. M.D. ANDERSON CANCER CENTER, Houston, TX, USA 


Challenges in the dosimetry of the new beams 

28 speaker 

CHALLENGES IN THE DOSIMETRY OF NEW BEAMS 

K. A. Johansson 1 

1 SAHLGRENSKA UNIVERSITY HOSPITAL, Radiophysics, Göteborg, Sweden 

Introduction to the symposium "Challenges in the dosimetry of the new 

beams" It is a challenge to determine the absolute dose and relative dose 

distribution created by some of the new treatment modalities e.g. tomotherapy, 

CyberKnife, IMAT and dynamic IMRT. These modalities create small 

fields, steep dose gradients and/or irradiation with beam rotation. Dosimetry 

in non-equilibrium for small fields, for dynamic field shape and for arc irradiation 

requires special attention. National and international dosimetry protocols 

recommend measurements in a reference condition usually a static beam 

with a 10 cm x 10 cm field size for determination of the absolute dose. Dosimetric 

parameters for converting ionization to absorbed dose are available in 

the protocol for this partial equilibrium condition. Many of the new treatment 

modalities have only small field sizes and can not produce a static beam of 10 

cm x 10 cm. However, no such recommendations exist for small beams. Measurement 

for the determination of the absorbed dose in non-equilibrium fields 

and/or arc techniques requires detectors with specific design of size and material 

as well as energy and angular dependence. Monte Carlo simulation is 

often needed in order to obtain correction factors for converting detector signal 

to absorbed dose. Monte Carlo simulation is also a suitable tool in order 

to determine the dose distribution with acceptable accuracy in homogeneous 

and heterogeneous medium for these new modalities. 

29 speaker 

VERIFYING THE DOSIMETRY OF INTENSITY MODULATED ARC 

THERAPY (IMAT) 

M. Iori 1 , E. Cagni 1 , M. Paiusco 1 , S. Riccardi 1 , A. E. Nahum 2 

1 

S. MARIA NUOVA HOSPITAL, Department of Medical Physics, Reggio 

Emilia, Italy 

2 

CLATTERBRIDGE CENTRE FOR ONCOLOGY, Department of Physics, 

Bebington, Merseyside, United Kingdom 

Intensity-modulated arc therapy (IMAT) is a technique for realizing intensitymodulated 

treatments (IMRT) using rotational beams in which the field shape, 

formed by a multileaf collimator, changes constantly during the delivery. Since 

the IMAT modality is still considered a novel technology, and as the IMAT 

plans consist of multiple arc beams, each containing many small, irregular 

S 11 

and off-axis field segments, guided by the gantry angle indices the overlapping 

of which generates complex fluence distributions, specific quality control 

is required for its clinical implementation. To ensure the accuracy of an 

IMAT treatment it is essential that an accurate quality assurance (QA) procedure 

of the normal arc delivery mode be performed, giving special attention 

to the mechanical and dosimetric verification of the complete treatment system. 

Moreover, the dosimetry comparison between measurement and calculation 

of each treatment plan has to be added to the previous checks. Many 

modalities have been proposed for the dosimetry of IMAT treatments, and 

the plan-related approach (the whole plan is transferred to and verified with a 

simple geometrical phantom) has been generally applied. To respond to the 

request to carry out two/three-dimensional dosimetry checks, radiographic 

or radiochromic film dosimetry, together with multiple ionization chambers, 

rather than polymer gels have played a crucial part in the commissioning 

and in the pre-clinical plan verification of the IMAT technique. Nowadays, 

the conventional procedures for IMRT treatment verification involve matrixdetectors 

(MD) and electronic portal image (EPID) devices. As it becomes 

easier to acquire and manage, in real-time, these dose-images, the use of 

these systems is rapidly increasing. While these systems are normally used 

for (fixed-gantry) IMRT dosimetry, and also an MD device coupled with a dedicated 

phantom has been extended to the IMAT treatments, the same is not 

the case for EPIDs. The aim of this talk is to present an overview of the 

IMAT verification modalities using different methods [conventional, IMAT simulated, 

monitor units check software] and detector devices, and in particular 

our experience in the use of an amorphous silicon EPID system to verify the 

IMAT plans (figure). Further, preliminary results of some dose verifications for 

IMAT beams simulated as gated and un-gated, as well as 3D dose-delivered 

reconstruction for some IMAT plans, using the MD or the EPID devices, will 

be shown. 

30 speaker 

DOSIMETRIC CONSIDERATION DURING CALIBRATION OF A 

TOMOTHERAPY UNIT 

P. Francois 1 

1 CURIE, Physics, Paris, France 

Current dosimetric protocols based on the absorbed dose (AAPM TG-51 and 

IAEA TRS-398 protocols) require calibration measurements under reference 

conditions. Some radiation treatment systems (helical tomotherapy, gamma 

knife, robotic arms) cannot produce reference conditions at all. For example, 

the helical tomotherapy (HT) system uses a narrow fan 6MV beam similar 

to a computed tomography (CT) scanner with the maximum field width of 5 

cm in the inferiorsuperior direction. Also HT source-to-axis distance (SAD) is 

85 cm and while the SSD of 100 cm could be achieved it is not a geometry 

that patients would be treated with. The absence of flattening filter changes 

the beam quality and profiles compared to 6MV beams produced by usual 

linear accelerators. These characteristics open a new problem in standard 

dosimetry. Calibration has to be performed under non reference experimental 

conditions. In order to solve this problem, both protocols can be extended 

by inclusion of the measured-to-reference conversion factor To determine this 

factor, basic dosimetric quantities, like stopping power ratios, mass attenuation 

coefficients and chamber correction factors have to be measured or calculated. 

If measurements are not feasible, accurate Monte Carlo modeling is 

required. Practical considerations for the extension of the different protocols 

are illustrated using the case of the helical tomotherapy radiation unit, where 

the typical calibration measurement conditions are the 40x5 cm field size and 

the 85 cm surface source distance, limited by the system design.


31 speaker 

THE PHYSICS OF THE DOSIMETRY OF ’SMALL’ FIELDS IN RADIO- 

THERAPY 

A. E. Nahum 1 

1 CLATTERBRIDGE CENTRE FOR ONCOLOGY, Department of Physics, 

Bebington, Merseyside, United Kingdom 

The emphasis in this talk is on "Physics" i.e. understanding the dosimetry 

of "small" fields in radiotherapy. The radiation qualities of principal interest 

are megavoltage photons but when is a field "small"? My choice is when the 

field width is insufficient for charged particle equilibrium (CPE) at its centre 

and/or when the size of commonly used detectors is an appreciable fraction 

of this width. Dosimetry is a much misused term; it is the determination of 

absorbed dose, whether it be by measurement or by calculation; the latter 

will inevitably involve an understanding of the relevant radiation transport processes. 

Small fields, in the above sense, are primarily involved when treating 

small tumours. Such small fields are often associated with stereotactic techniques 

(originally confined to the head but nowadays increasingly employed 

in the lung). As one gradually decreases the field size, for a given number 

of monitor units (MU), the dose on the central axis (or "output factor"), at the 

depth, say, of Dmax, decreases, at first very gradually, and then, below a certain 

field diameter (or side length of a square field), very rapidly. The initial 

gradual decrease is principally due to the decreasing contribution of scattered 

photons. The rapid decrease is due primarily to a lack of (lateral) scattering 

equilibrium as the field width becomes comparable to that of the maximum 

range of secondary electrons (e.g. Ahnesj et al) , but there is also the effect 

of source occlusion parts of the extended source become shielded or blocked 

by the collimator (i.e. jaws). What happens if we now try to measure the dose 

in such small fields? This will depend on the type of detector. Perhaps the 

most obvious effect is due to detector size. All detectors yield the signal averaged 

over their volume; a dose that is changing rapidly in any direction 

requires a detector with small dimensions in that direction. The ionisation 

chambers conventionally used for absolute dose determination (’Farmer’ or 

plane-parallel geometry) are too large so either the so-called pinpoint chamber 

is required or, better still, diodes or diamond detectors. As an example, 

recently Scott et al have shown that, in a 15 MV photon beam, unshielded 

diodes appear to agree best with Monte-Carlo simulation, down to field sizes 

of 0.5 cm. These new results will be discussed in detail.Detectors are generally 

calibrated (in terms of absolute dose in water) in reference conditions i.e. 

at large field sizes. Apart from the averaging effect due to their size, should 

we expect other correction factors to be field-size dependent? For ion chambers 

it has been shown (e.g. by Andreo) that water/air stopping-power ratios 

vary only weakly with field size in photon beams; the lack of CPE per se is 

not a problem as Bragg-Gray (BG) behaviour does not involve any assumptions 

about equilibrium. For high-density non-BG cavities such as diodes or 

diamond detectors another potential effect may come into play, which we can 

term forced equilibrium the much shorter electron ranges in the detector will 

cause the deviation from CPE to be less, resulting in an overresponse compared 

to the dose in water.A very different but potentially important type of 

"small-field dosimetry" issue is related to the way in which an IMRT ’optimizer’ 

computes the relative weights of the different narrow beamlets during 

the inverse-planning process. If the (3D) dose distribution from an individual 

beamlet is seriously in error then the relative beam weights required to 

deliver the desired dose distribution will not be correct, nor will the delivered 

dose distribution correspond to that of the treatment plan. Das IJ, Ding G and 

Ahnesj A, Small fields: non-equilibrium radiation dosimetry Med. Phys. 35 

206-15, 2008Scott A, Nahum A and Fenwick J, Using a Monte Carlo model to 

predict dosimetric properties of small radiotherapy photon fields, Med. Phys. 

in press 

Head and neck cancer: skin and mouth care and 

diet 

32 speaker 

COMBINATION OF ANTI EGFR AGENTS AND RADIOTHERAPY IN 

ADVANCED H&N CANCERS: TREATMENT OF SKIN REACTIONS 

G. Vandevelde 1 , I. De Jaegher 1 , S. Nuyts 1 

1 UNIVERSITY HOSPITAL GASTHUISBERG, Department of Radiotherapy, 

Leuven, Belgium 

A high number of head and neck tumors (90-100%) show EGFR expression. 

This EGFR expression is an indicator of poor prognosis, increased metastasic 

potential and decreased survival in many cancers. Inhibition of the EGFR 

on this cancer cells may inhibit its growth or progression. The combination of 

Cetuximab, a monoclonal antibody that has the ability to block the EGFR expression, 

and radiotherapy in this patient group has demonstrated to improve 

local control and disease free survival. Patients treated with this concomitant 

regimen will develop several a-specific/general side effects (eg nausea 

, sweating, general ill feeling, higher sensitivity to sunlight). More important 

are some specific local reactions such as white patches in their mouth or lips, 

an acne-like skin rash, dry cracked or swollen skin in- and outside the treated 

area. Due to the high dose of radiotherapy (70 Gy) grade 2 and grade 3 skin 

reactions are often observed after 4 to 5 weeks (50 Gy). The combination with 

EGFr targeted agents will lead to even more severe skin toxicity. Special attention 

should be given to this complex problem since a combination of local 

radiotherapy related skin reactions with additional skin damage due to Cetuximab 

might decrease the patient’s general condition resulting in intensive 

local care and prolonged healing, treatment interruption and hospitalization. 

A specific skin care protocol has been developed and implemented for this 

patient population. On top of the recommendations, given in a conventional 

skin care protocol, additional specific advices are described. Since healing 

time of skin due to the additional damage has prolonged up to 6-8 weeks after 

completing radiotherapy, radiation therapists play a crucial role coordinating 

care for these patients throughout the whole process. 

33 speaker 

REVIEW CLINICS 

L. Hallissey 1 

1 CORK UNIVERSITY HOSPITAL, Department of Radiation Oncology, Cork, 

Ireland Republic of 

Background:Patients undergoing a course of radiation therapy experience 

side-effects which are monitored daily by the radiation therapist team on the 

treatment machines, and weekly by the medical team. In our department 

there are a large numbers of patients, a shortage in radiation oncology consultant 

staff and currently no specialist registrar training programme. This has 

resulted in an excessive workload with reduced time available for patient consultation 

and delay in implementing site specialisation within the department. 

In addition the publication of major reports influenced how we plan to deliver 

an optimum service in the future. These reports are the European Working 

Time Directive (2002) which laid down regulations with respect to the working 

hours of Non Consultant Hospital Doctor. The Hanley Report (2003) which 

emphasised areas where other non-medical staff were well placed to deliver 

aspects of a quality health service and the Strategy for Cancer Control (2006) 

which advocated increased timely radiation therapy information for patients. 

Materials and Methodology: In the context of the multiple factors outlined 

above it was agreed that Cork University Hospital would undertake a pilot 

project evaluating the effectiveness of radiation therapists facilitating the 

weekly on treatment review clinics for patients with breast and prostate cancer. 

These two groups of patients together represent 40% of the workload in 

the department. Funding was made available by the charitable organisation 

"Aid Cancer Treatment (ACT) " for staff to undertake additional education and 

to visit a number of centres in the UK where radiation therapist review clinics 

have been established for some time (the Irish Cancer Society took over funding 

the in 2007). The clinics commenced in January 2005 and regular review 

and audit was carried out. In July 2007 a series of questionnaires were sent 

out to patients, nurses, radiation oncologists and radiation therapists to elicit 

their opinion on the effectiveness of the model. 

Results: The responses to the patient questionnaire were 100% affirmative 

of the service offered in all areas surveyed. From the health professionals 

surveyed there was full agreement that, from the general perspective, side 

effects were managed appropriately and that the radiation therapists were an 

appropriate professional group to carry out these clinics. However when the 

side effects were identified individually there was some uncertainty in relation 

to arm mobility management (15%) and recall of treatment information (9%). 

A small minority of health professionals were unsure whether the service was 

enhanced and the needs of patients met (4% in each instance) and 50% did 

not feel that their workload was reduced as a result. 

Conclusion: The breast and prostate review clinics are now part of the routine 

practice of the department and seven radiation therapists are currently 

trained in review clinic facilitation. The level of satisfaction by both patients 

and other healthcare professionals is very high overall. The review clinics 

have been successful in reducing waiting times for patients to be seen of approximately 

30 minutes, in increasing the allocation of time for patients in the 

clinic, in an improved level of satisfaction for patients and a higher level of 

collaboration between the clinicians and the radiation therapists. The reduction 

in review workload for clinicians has allowed them more time to deal with 

complex or urgent reviews and new patient clinics. The radiation therapist led 

review clinics have been seamlessly integrated into the overall patient review 

process in Cork University Hospital and have been shown to complement 

existing practice. In November 2007 the initiative received the Irish Health 

Service Executive Achievement Award for new developments. 

References: 

Chesser, S., Bowman, K. & Philips, H. (2002) The European Working Time 

Directive and the training of surgeons. BMJ, 325(suppl), s69. 

Hanley Report (2003) Report of the National Task Force on Medical Staffing. 

Health Service Executive (2006) A Strategy for Cancer Control in Ireland.


34 speaker 

SMOKING DURING RADIOTHERAPY, ACUTE AND LATE TOXICITY 

L. Sharp 1 

1 KAROLINSKA UNIVERSITY HOSPITAL, Dep of Oncology/Radiotherapy, 

Stockholm, Sweden 

Several studies have shown that smoking prior to cancer diagnosis may be 

a risk factor for negative treatment outcome and even survivorship for some 

groups of patients. There are also published studies showing that smoking 

during radiotherapy (RT) can have a negative effect on the results due to tumour 

hypoxia. Some studies also indicate an increased risk for both acute 

and late toxicity, from smoking during RT. The acute toxicity is mainly seen in 

the irradiated skin and mucosa. The late toxicity seenas a result of smoking 

during RT in the published studies are conditions such as lung cancer, MI, 

fibrosis etc. In this session the author will give an overview of the published 

research in this field, for different groups of patients, and also suggest how 

clinicians can give adequate information and support to cancer patients regarding 

smoking cessation. Despite obvious benefits, few cancer patients are 

offered systematic help with smoking cessation. During this session hinders 

and benefits with smoking cessation integrated in the care at a RT-unit will 

also be discussed. 

High Risk Prostate Cancer 

35 speaker 

MOLECULAR DETERMINANTS OF THE CLINICAL BEHAVIOUR IN 

PROSTATE CANCER. THE MOLECULAR BIOLOGISTS POINT OF 

VIEW. 

Z. Culig 1 

1 INNSBRUCK MEDICAL UNIVERSITY, Department of Urology, Innsbruck, 

Austria 

Prostate cancer is a relatively slow growing tumor that could be cured if detected 

in early stages. However, small cancers that will not become clinically 

significant are being treated in some institutions. Prostate cancer is a heterogenous 

disease in which the expression of androgen receptor and target 

genes may vary between tumor samples obtained from one patient. Although 

many laboratories attempt to improve molecular diagnostics and find novel 

markers associated with more aggressive disease, it is still difficult to use data 

other than those describing Gleason score for clinical decisions. One reason 

for that is the multifunctional nature of action of some steroid hormones and 

cytokines. In this presentation, the focus will be on pleiotropic regulation of 

cellular events by androgens and interleukin-6 (IL-6). Androgenic activation of 

the androgen receptor (AR) is associated with biphasic regulation of cellular 

proliferation and a concentration-dependent effect on differentiation. AR expression 

in tumor cells may be increased due to adaptive changes that lead to 

enhanced receptor sensitivity. In contrast, epigenetic changes in the AR gene 

promoter are found in more aggressive tumor cells. Current therapy with androgen 

ablation or anti-androgens is initially very efficient, however, prostate 

cancer progression occurrs in a number of patients. The mechanisms are in 

part related to AR. For example, there may be point mutations or changes 

in coactivator/coreppressor ratio. Expression of some co-activators of the 

AR increases during androgen ablation and these proteins may also exhibit 

AR-independent effects on tumor cell invasion. The presence of androgens 

is required for the maintenance of differentiation function of prostate cancer 

cells. Therapies for prostate cancer do not distinguish between inhibition of 

the proliferation and differentiation function. IL-6, a cytokine whose expression 

is increased in prostate cancer tissue and patients sera, is a clinically 

important regulator of prostate cancer cell growth. It may inhibit proliferation 

and, in other cells, act as an anti-apoptotic cytokine. Its action is mediated 

through signaling pathways of Janus kinase/signal transducers and activator 

of transcription factors, mitogen-activated protein kinase, and Akt kinase. The 

effects of IL-6 are under control of suppressors of cytokine signaling (SOCS). 

These growth regulators seem to be clinically relevant because of their feedback 

role in signaling pathways of steroids and cytokines. 

36 speaker 

ASSESSMENT OF LYMPH NODE INVOLVEMENT IN PROSTATE 

CANCER - UNDERESTIMATED RISK? 

D. Weckermann 1 

1 KLINIKUM AUGSBURG, Department of Urology, Augsburg, Germany 

The rate of positive pelvic lymph nodes reported in open extended pelvic 

lymph node dissection (PLND) series varies, depending on the population 

studied, the number of lymph nodes removed and the histopathological analysis 

of lymph node specimens. Current nomograms can estimate the risk 

of lymph node metastasis in prostate cancer. But these staging tools of- 

S 13 

ten underestimate the risk of lymph node involvement especially in high 

risk disease because of postoperative upstaging and upgrading and the fact 

that most nomograms are based on results of limited PLND. Sentinel lymph 

nodes (SLN) are defined as any lymph nodes which receive direct lymphatic 

drainage from the primary tumor site. They can be detected by preoperative 

injecting a radioactive tracer (99m technetium nanocolloid) into the prostate. 

When the SLN is/are negative, the other lymph nodes are negative, too. Our 

results of SLN dissection in more than 1,500 men with clinically organ confined 

prostate cancer have shown that SLN dissection has a high sensitivity in 

detecting positive nodes (> 95%) while the false negative rate is low (< 5%). 

In high risk prostate cancer positive pelvic lymph nodes were found in more 

than 40%. These lymph node metastases were predominantly located along 

the internal iliac artery, followed by the external iliac vein and the obturator 

fossa. When the SLN is/are positive, secondary pelvic lymph nodes can be 

positive, too. In high risk disease 26 out of 94 men had positive non sentinel 

lymph nodes (NSLN), too. These positive NSLN were located close to SLN, 

but also on the contra lateral site of the pelvis. SLN dissection in prostate cancer 

is an excellent staging tool. In high risk prostate cancer a high percentage 

of men have positive NSLN in case of positive SLN. Therefore SLN dissection 

should be combined with extended PLND in order to obtain an exact lymph 

node staging and probably prolong PSA progression free survival. 

37 speaker 

ADJUVANT RADIOTHERAPY OF THE PELVIC LYMPH-NODE AREAS 

A. Zapatero 1 

1 HOSPITAL UNIVERSITARIO DE LA PRINCESA, Department of Radiation 

Oncology, Madrid, Spain 

The combination of high-dose radiotherapy and androgen deprivation for patients 

with high-risk prostate cancer has become a standard of care on the 

basis of the results of multiple randomized trials. Intuitively, elective pelvic 

node irradiation (EPNI) in this subgroup of high-risk disease could be effective 

in sterilizing occult nodal metastasis and, logically, in improving diseasefree 

survival (DFS) and overall survival (OS). This hypothesis has been the 

cornerstone for the incorporation of EPNI in most clinical trials in high-risk 

prostate cancer. However, if lymph node involvement were tantamount to 

distant metastasis spread instead of being a spring-board, EPNI would be 

less useful. Furthermore, hormone manipulation could address microscopically 

involved lymph nodes. Several retrospective and prospective randomized 

trials have been conducted in the past years with controversial results. 

Many of them were old, heterogeneous studies developed in the pre-PSA 

era and probably included patients not suitable for this purpose. The data 

from modern randomized trials like the updated results from RTOG 9413 and 

the preliminary report from GETUG-01 trial have thrown the discussion wide 

open again. While RTOG 9413 trial have shown an unexpected interaction 

between the timing of hormonal therapy and radiation field size making the 

analysis of this study more complex and no conclusive, the preliminary results 

of the French study did not lead to any improvement in progression-free 

survival with EPNI. Current issues like the realistic amount of benefit, definition 

of target volumes, radiation dose and therapeutic index of EPN, its 

biological interaction and timing with hormone therapy and the use of lymph 

node biomarkers, are crucial aspects that need to be conclusively answered 

in high-risk prostate cancer. PFS: progression-free survival; OS: overall survival; 

NS: not significant; WPRT: whole pelvic radiotherapy; PORT: prostate 

only radiotherapy; NHT: neoadjuvant hormone therapy; AHT: adjuvant hormone 

therapy. 

38 speaker 

RADIATIONS ROLE IN PATIENTS WITH PN+ PROSTATE CANCER 

C. Lawton 1 

1 MEDICAL COLLEGE OF WISCONSIN, Milwaukee, USA 

Abstract not received.


Shaping the radiotherapy future: development of 

radiation oncology 

39 speaker 

THE EPIDEMIOLOGICAL PICTURE AT A EUROPEAN LEVEL AND 

THE "AGENT TIME-BOMB" 

J. Coebergh 1 

1 ERASMUS UNIVERSITY, Rotterdam, Netherlands 


40 speaker 

THE FUTURE DEVELOPMENT OF OUR SPECIALTY IN EUROPE 

J. W. Leer 1 

1 RADBOUD UNIVERSITY NIJMEGEN MEDICAL CENTER, Medical Center, 

Nijmegen, Netherlands 

We observe a couple of changes in Radiation Oncology which need to be discussed 

and this should result in a strategy for ESTRO.Infrastructure for radiotherapy 

is expensive and creating new bunkers is time consuming.Therefore 

a good planning preferably on a national basis is necessary.A major change 

in indications for radiotherapy especially in one of the most treated tumour 

types can have a great impact on such a planning. Radiation Oncology is 

also again on a cross road.An example of these type of calculations will be 

presented In the seventies of the last century we have seen that radiotherapy 

split from radiology and became independed specialty in most countries. Today 

we see that image guided radiotherapy has become state of the art and 

that radiation oncologists are using more and more MRI, CT, S-PECT and 

PET-CT for treatment planning. At the same time there is hardly any tumour 

type which is not treated with a combined modality.Can radiotherapy remain 

standing alone or should we merge with radiology or medical oncology?The 

generalist in radiation oncology is disappearing. Subspecialisation in oncology 

is entering the discipline. This also has consequences for the minimum 

size of a department and the organization of oncology in a nation or region. 

Low volume radiotherapy will lose qualityWe also can observe a shift in responsibilities 

between doctors and technologists. This can be seen also in 

other disciplines and has let to extensive discussions in UEMS on the definition 

of a medical act and redefining the role of the physician. It also could have 

consequences for manpower planning. Finally all of these changes will have 

an impact on our curriculum. Do we need a common trunk with radiology or 

medical oncology? Do we need subspecialisation in the training programme? 

But also the way we train will change and will be competency based. 

41 speaker 

THE POTENTIAL FOR STRATEGIC DEVELOPMENT OF RADIATION 

ONCOLOGY SERVICES AT A NATIONAL LEVEL: OPPORTUNITIES 

AND PITFALLS. 

D. Hollywood 1 

1 TRINITY COLLEGE DUBLIN, Academic Unit of Clinical and Molecular 

Oncology, Dublin, Ireland Republic of 

Few international benchmarks for the development of radiation oncology services 

exist and almost no literature is available to guide national authorities on 

the development of newer radiation technologies such as IMRT or IGRT. Most 

countries have relied on historically limited guidelines that have attempted 

to base service development on estimates equipment or personnel. In addition 

the cost-benefit and cost-utility benefits of radiation therapy, although 

widely recognized and suggested, have also been poorly developed. It is 

highly possible that a direct consequence of this lack of knowledge is the 

slow development and multi-annual investment in radiation oncology in many 

countries that are significantly dependent on strategic public funding and investment.Recent 

economic models for national or large-scale radiation oncology 

service development/procurement have pursued new costing options 

that have more frequently been utilized in other governmental fiscal plans, 

including "public-private" partnership (PPP/P3). The methodology for undertaking 

this magnitude of multi-annual investment is poorly developed within 

the discipline of Radiation Oncology. In addition the long term cost and of this 

model of financing radiation oncology is unclear. These uncertainties may 

ultimately impact on the nature of service delivery, patient care, and possibly 

the future capacity to expand additional radiation oncology services particularly 

with rapidly changing technologies for example the potential option of 

rapidly implementing image guided RT, biologically optimized RT, and/or particle 

therapies.The newer finance models also place a new onus on Radiation 

Oncologists to more clearly define their professional role and responsibilities 

within the increasingly complex range of treatment: it will be a clear requirement 

to define the specific roles of key personnel in a number of developing 

areas including the potential future integration of functional imaging, and 

molecular modification approaches to RT.Since 1997 Ireland has pursued a 

complex process leading to a proposed National Programme for Radiation 

Oncology using a Public Private Partnership model. The issues, complexities 

and opportunities of this approach will be presented. 

Partial breast irradiation 

42 speaker 

CAN WE YET DEFINE THE CANDIDATES BETTER FOR PARTIAL 

BREAST IRRADIATION? 

C. Polgár 1 

1 NATIONAL INSTITUTE OF ONCOLOGY, Department of Radiotherapy, 

Budapest, Hungary 

In the last two decades accelerated partial breast irradiation (APBI) has been 

intensively evaluated in Phase I and II studies as a possible alternative to 

conventional whole breast irradiation (WBI). Majority of these trials using 

conservative patient selection criteria and proper treatment technique were 

successful in yielding an annual local recurrence rate in the range of 0 to 

1.3%. The 5-year results of the Hungarian single institutional Phase III trial 

also demonstrated the non-inferiority of APBI compared to 50 Gy WBI. Despite 

variability in selection criteria, the majority of women treated within these 

trials were > 40 years old, presented with node negative invasive ductal carcinomas 

up to 3 cm, without extensive intraductal component (EIC), and resected 

with clear margins. Based on available experience both the American 

Brachytherapy Society (ABS) and the American Society of Breast Surgeons 

(ASBS) published their guidelines for patient selection (Table 1.)However, 

controversy exists regarding the possible extension of selection criteria 

including patients younger than 50 (or 45) years, women with lobular carcinomas, 

EIC positive tumors, or with one to three positive nodes without 

extracapsular extension. Ongoing clinical research actually focuses on better 

definition of candidates for APBI (Table 2.). As data from ongoing multicentric 

Phase III trials mature, guidelines for patient selection should be revised 

and might be extended. However, until additional long-term outcome reports 

of Phase III trials are available, conservative patient selection criteria (as defined 

by the ABS and ASBS) should be considered for selecting candidates 

for APBI. 

43 speaker 

LATE NON SKIN TOXICITY OF APBI 

O. J. Ott 1 

1 UNIVERSITY HOSPITALS OF ERLANGEN, Erlangen, Germany 



44 speaker 

DOES SKIN DOSE MATTER? 

P. Niehoff 1 

1 UNIVERSITY HOSPITAL S-H CAMPUS KIEL, Kiel, Germany 


Next steps in molecular targeting for radiotherapy 

45 speaker 

ANTI-ANGIOGENESIS AND THE HER FAMILY AS TARGETS 

D. Zips 1 

1 UNIVERSITY HOSPITAL, TU DRESDEN, Department of Radiation Oncology, 

OncoRay Radiation Research Center, Dresden, Germany 

Biological targeting is a proven principle to improve outcome after radiotherapy. 

Conceptually successful targeting strategies focus on biological mechanisms 

that contribute to radiation resistance of tumours or radiation sensitivity 

of normal tissues. Preclinical as well as clinical evidence suggests that 

tumour angiogenesis and signaling via the human epidermal growth factor 

receptors (HER family) are promising targets for radiation oncology. Biological 

rationale for combination of anti-angiogenic/anti-HER therapies combined 

with radiotherapy, recent preclinical and clinical data for efficacy and biological 

mechanisms of interaction as well as novel developments for targeting will 

be reviewed. 

46 speaker 

RADIOSENSITIZATION: EGFR AND BEYOND 

G. Lammering 1 

1 UNIVERSITY HOSPITAL MAASTRICHT, Radiation Oncology (MAASTRO 

Clinic), Maastricht, Netherlands 

In our efforts to improve the clinical outcome of radiotherapy for solid tumors, 

three major radioresistance mechanisms have to be taken into account: Tumor 

cell hypoxia/ angiogenesis, intrinsic cellular radiosensitivity and tumor 

cell proliferation. The EGFR familiy and its asscociated signal- transduction 

pathways have been demonstrated to be associated with these three major 

mechanisms. Consequently, anti-EGFR targeted approaches in combination 

with radiotherapy have been tested and first clinical results are promising. 

However, despite this first success, only a few patients will ultimately benefit 

with an increased locoregional control, either because of a varying efficiency 

of the EGFR-directed therapy, or because of a non- sensitive molecular phenotype. 

Furthermore, solid tumors are a very heterogeneous disease. Therefore, 

complementary tests are needed to better select patients. One approach 

should be drug monitoring of the molecular targeted agent with imaging in order 

to better proof efficent drug delivery in the tumor, another way could be 

the development of new markers for EGFR- directed therapies, e.g. markers 

of PI3-K/Akt activation and markers of certain mutations in the PI3-K and/or 

MAPK pathway. A further improvement in the radiosensitization of solid tumors 

might be achievable through the combination of anti-EGFR therapies 

with chemotherapeutic agents, like gemcitabine or platinum, both of which 

are known to stimulate EGFR phosphorylation. Inhibition of this effect with 

EGFR inhibitors could therefore potentiate cytotoxicity and radiosensitization. 

Another way of further enhancing the effectiveness of anti-EGFR therapy during 

radiotherapy could be the additional modulation of the PI3-K/Akt pathway, 

especially in tumors that have elevated PI3-K/Akt cascade activity. Given the 

fact that the PI3-K/Akt pathway not only controls EGFR family- and IGF1-Rrelated 

cytroprotective radiation responses, but also two important tumor-cell 

responses to hypoxia, namely the enhanced VEGF and HIF-1alpha expression 

makes this pathway even more attractive for targeted treatment strategies. 

In preclinical studies, specific inhibition of PI3-K/Akt has been achieved 

by the use of HIV-protease inhibitors, which also resulted in enhanced radiosensitization. 

One downstream cell-growth regulator of the PI3-K/Akt pathway, 

the mammalian target of rapamycin (mTor) has also already successfully 

been used preclinically for radiosensitization. Nevertheless, HIF-1alpha and 

HSP-90 also represent central molecules for hypoxic responses, proliferation 

and repair signalling, which are attractive targets for radiosensitization. Taken 

together, future EGFR- related developments in radiosensitization will include 

complementary testing and combinations with other targeted agents. 

47 speaker 

S 15 

THE ROLE OF HOMOLOGOUS RECOMBINATION IN THE RE- 

SPONSE TO IONIZING RADIATION 

S. N. Powell 1 

1 WASHINGTON UNIVERSITY SCHOOL OF MEDICINE, St. Louis, USA 

The major biological effects of ionizing radiation are mediated through doublestrand 

damage to DNA. The two main pathways of DNA repair for these 

lesions are non-homologous end-joining (NHEJ) and homologous recombination 

(HR). Until recently, the major double-strand break repair pathway in 

mammalian cells was thought to be NHEJ, but recent evidence has shown 

that HR does contribute significantly to the repair of double-strand damage. 

Double-strand damage can affect cells post-replication, where the sister chromatid 

is available for repair by HR. Inactivation of HR shows a predominant 

effect on S and G2 phase radio-resistance. However, an additional role for HR 

is in the repair of one-ended double-strand breaks that occur at a collapsed 

replication fork, which maybe the major role of HR in cells. Cancer cells potentially 

depend on HR for double-strand break repair more than normal cells 

because of their higher proliferative fraction, with more cells in the S and G2 

phases of the cell cycle. In addition, genetic changes in cancer cells, such 

as the loss of p53 function, can remove the suppression of HR that normally 

exists in non-transformed cells. The conclusion from these observations is 

that cancerous cells will depend on HR for the repair of double-strand damage 

from ionizing radiation significantly more than the adjacent normal cells, 

even if they are proliferative normal cells. Thus, targeting homologous recombination 

should be an excellent strategy for enhancing the therapeutic gain of 

ionizing radiation. In addition, a number of cancer cells have lost the function 

of proteins involved in HR, such as BRCA1 and BRCA2 in breast and ovarian 

cancers. We have developed bio-assays to measure the function of HR in 

human tumor samples, since the loss of HR function leaves the cancer cells 

vulnerable to specific cytotoxic and biological agents. 

48 speaker 

EXPLOITING DNA REPAIR AS TARGET FOR IMPROVING RADIO- 

THERAPY 

T. Helleday 1 

1 UNIVERSITY OF OXFORD, Department of Radiation Oncology and Biology, 

Oxford, United Kingdom 

Radiotherapy causes highly toxic DNA double-strand breaks (DSB) that result 

in cell death. Normally, DSBs are repaired preferentially by non-homologous 

end joining (NHEJ) to prevent cell death, with homologous recombination 

(HR) as a back up pathway for DSBs that are difficult to simply ligate. Furthermore, 

DNA single-strand break (SSB) repair and DNA damage signalling 

pathways are also critical in the reponse to ionizing radiation (IR). A deficiency 

in DNA repair or DNA damage signalling radiosensitise cells to IR and 

inhibitors of NHEJ, ATM and PARP are currently exploited to radiosensitise tumours 

in preclinical models. Inhibitors of DNA repair may be used to minimise 

off-target effects following IR, but their overall success depend on their ability 

to selectively radiosensitise malignant tissue. DNA repair and DNA damage 

signalling pathways are often altered in cancers through somatic or inherited 

mutations. For instance BRCA1 or BRCA2 mutated breast or ovarian cancers 

are defective in HR, which also make them hypersensitive to inhibitors of 

SSB repair, such as inhibitors of poly(ADP-ribose)polymerase. The success 

of future use of DNA repair inhibitors as radiosensitisers may thus depend on 

the tumour DNA repair and damage signalling status. 

Adaptive strategies in IGRT 

49 speaker 

ADAPTIVE BIOLOGICAL IMAGE-GUIDED RT IN HNSCC: HOW FAR 

ARE WE FROM REALITY? 

X. Geets 1 , J. A. Lee 2 , A. Bol 2 , M. Lonneux 3 , V. Grégoire 1 

1 

CLINIQUES UNIVERSITAIRES SAINT-LUC, UCL, Radiation Oncology, 


2 

CLINIQUES UNIVERSITAIRES SAINT-LUC, UCL, Molecular Imaging and 

Experimental Radiotherapy Lab., Brussels, Belgium 

3 

CLINIQUES UNIVERSITAIRES SAINT-LUC, UCL, Nuclear Medicine, 


In recent years, the impressive progress performed in imaging, computational 

and technological fields have made possible the emergence of image-guided 

radiation therapy (IGRT) and adaptive radiation therapy (ART). The accuracy 

in radiation dose delivery reached by IMRT offers the possibility to increase locoregional 

dose-intensity, potentially overcoming poor tumor control achieved 

by standard approaches. However, before implementing such a technique in 

clinical routine, particular attention has to be paid at the target volumes defi-


nition and delineation procedures to avoid inadequate dosage to TVs/OARs. 

In head and neck squamous cell carcinoma (HNSCC), the GTV is typically 

defined on CT acquired prior to treatment. However, by providing functional 

information about the tumor, FDG-PET might advantageously complete the 

classical CT-Scan to better define the TVs. Similarly, re-imaging the tumor 

with an optimal imaging modality might account for the constantly changing 

anatomy and tumor shape occurring during the course of fractionated radiotherapy. 

Integrating this information into treatment planning might ultimately 

lead to a much tighter dose distribution.From a methodological point of view, 

the delineation of TVs on anatomical or functional images is not a trivial task. 

Firstly, the poor soft tissue contrast provided by CT comes out of the large interobserver 

variability in GTV delineation. In this regard, we showed that the 

use of consistent delineation guidelines significantly improved consistency 

between observers, either with CT and with MRI. Secondly, the intrinsic characteristics 

of PET images, including the blur effect and the high level of noise, 

make the detection of the tumor edges arduous. In this context, we developed 

specific image restoration tools, i.e. edge-preserving filters for denoising, and 

deconvolution algorithms for deblurring. This procedure restores the image 

quality, allowing the use of gradient-based segmentation techniques. This 

method was validated on phantom and patient images, and proved to be more 

accurate and reliable than threshold-based methods.Using these segmentation 

methods, we proved that GTVs significantly shrunk during radiotherapy 

in patients with HNSCC, independent of the imaging modality used (MRI, 

CT, FDG-PET). No clinically significant difference was found between CT and 

MRI, while FDG-PET provided significantly smaller volumes than those based 

on anatomical imaging. Refining the target volume delineation by means of 

functional and sequential imaging ultimately led to more optimal dose distributions 

to TVs with subsequent soft tissue sparing.In conclusion, we demonstrated 

that multi-modality-based adaptive planning is feasible in HN tumors 

and potentially opens new avenues for dose escalation strategies. However, 

as a high level of accuracy is required with such an approach, the delineation 

of TVs however requires particular attention. 

50 speaker 

CYBERKNIFE TREATMENTS: REAL-TIME ADAPTATION TO MOVING 

TARGETS 

M. Hoogeman 1 , J. Nuyttens 1 , J. Pöll 1 , J. B. Prévost 1 , P. Levendag 1 , B. 

Heijmen 1 

1 ERASMUS MC - DANIEL DEN HOED CANCER CENTER, Department of 

Radiation Oncology, Rotterdam, Netherlands 

Synchrony, which is part of the CyberKnife robotic radiosurgery treatment unit 

(Accuray Inc., Sunnyvale, US), is a real-time tumor tracking system for tumors 

that move with respiration. Motion compensation is achieved by the real-time 

updating of the beam position by means of a robotic manipulator. To steer 

the beam to the right location, Synchrony combines a non-continuous signal, 

i.e. in-room stereoscopic X-ray images of the internal target position, with a 

continuously recorded breathing signal, i.e. LEDs attached at the patient’s 

chest or abdomen. A linear or polynomial correlation model relates both signals. 

This model is built just prior to each treatment fraction and regularly 

updated throughout the treatment.Phantom experiments with a motion table 

have proven that the accuracy of the respiratory motion tracking system is 

0.7 ± 0.3 mm. In real patient treatments this accuracy might be declined 

by irregular breathing, varying phase-relationships between the internal and 

external breathing signal, and rapid base-line shifts. To quantify the clinical 

accuracy, data in log files of 47 lung cancer patients (167 treatment fractions), 

previously treated with respiratory motion tracking, were analysed. The logs 

were filtered to remove parts for which the data and the delivery of a clinically 

used beam did not match in time. For each treatment fraction, correlation 

model errors were quantified by its mean and standard deviation. The measured 

correlation model errors were small, with overall mean values for the 

involved 167 fractions below 0.2 ± 0.3 mm (1 SD) for all directions. Standard 

deviations describing intra-fraction variations around the fraction mean error 

were 0.9 mm (range: 0.2 - 1.9 mm) for SI, 0.7 mm (0.1 - 1.9 mm) for LR, and 

0.9 mm (0.2 - 2.5 mm) for AP. Without the use of motion tracking these variations 

would have been 2.9 mm (0.2 - 8.1 mm), 1.4 mm (0.2 - 5.5 mm), and 

1.7 mm (0.2 - 4.4 mm).The response of the respiratory motion compensating 

system is not instantaneously. Data processing and communication and 

the inertia of the system, causes a time lag of 115 ms. A prediction model 

[1] is used to compensate for this small time delay. The prediction error was 

quantified for the 167 treatment fractions by subtracting the predicted position 

from the actual measured position after 115 ms. The mean prediction 

error was negligibly small for all directions. The mean SD of the prediction 

error was 0.4 ± 0.3 mm in the SI direction (range: 0.0 - 1.6 mm). The SD 

was highly correlated with motion amplitude (R=0.9), where the error in the 

SI direction was 0.07 times the motion amplitude.In conclusion, the log file 

analyses have proven for real clinical cases that the geometrical error due 

to respiratory motion is dramatically reduced by the application of respiratory 

motion tracking. Especially for tumours with large motion amplitude, respiratory 

motion tracking considerably reduces the safety margin, and thus the 

treated volume.[1] Sheng et al., Proceedings of the Ninth IASTED International 

Conference Hawaii, 2007, 459-64. 

51 speaker 

ADAPTIVE STRATEGIES IN IG(IM)RT USING MLC ADAPTATIONS 

S. Webb 1 

1 INSTITUTE OF CANCER RESEARCH, Joint Department of Physics, London, 

United Kingdom 

Now that the methods to plan and deliver intensity-modulated radiation therapy 

(IMRT) are very well worked out and indeed much used in clinical practice, 

attention is focusing on aspects of the chain of processes that ultimately 

determine the accuracy of the physical basis of radiation therapy. One major 

concern is the treatment of moving body tissues. It has been observed that 

many targets move in a completely non stationary way. That is, the motion 

itself is irregular. There can be variations in amplitude, periodicity and baseline 

shifts during any one delivery fraction and indeed these variations may be 

themselves different between fractions. Moreover within the delivery of any 

one fraction the intrafraction motion may be different for the delivery of each 

beam comprising that fraction. A particular challenge is the variable motion 

of lung tumours. Techniques for coping with variable intrafraction organ motion 

when delivering intensity-modulated radiation therapy (IMRT) have been 

developed. Two strategies have been identified. [1] A strategy by which the 

fluence delivered up to a particular fraction is subtracted from the required 

total-course planned fluence to create an adapted residual fluence for the next 

fraction. This requires that the fluence already delivered can be computed, 

knowing the intrafraction motion during each fraction. If the adaptation is unconstrained, 

as would be required for perfect delivery of the planned fluence, 

then the individual fractional fluences would become unphysical, with both 

negative components and spikes. Hence it is argued that constraints must be 

applied; firstly positivity constraints and secondly constraints to limit fluence 

spikes. Additionally it is shown to be helpful to constrain other quantities. The 

power of the strategy is that it adapts to the (potentially variable) moving geometry 

during each fraction. It is not a perfect delivery but it is always better 

than making no adaptation. The fractionated nature of radiation therapy is 

thus exploited to advantage. The fluence adaptation method does not require 

impractical re-planning at each fraction but this imposes limitations. [2] In a 

second adaptive method the motion must be measured or modelled and the 

cumulative dose error after each fraction can be made the basis of computing 

a "next fraction" fluence map in such a way as to promote a close agreement 

between the final dose delivered and that planned. The advantage of this 

technique is that there is no need for any adaptive re-planning. 

52 speaker 

AUTOMATIC SEGMENTATION AND TARGETING OF ANATOMIC 

CHANGES AND SHIFTS AT THE LINAC 

P. Keall 1 

1 STANFORD UNIVERSITY SCHOOL OF MEDICINE, Department of Radiation 

Oncology, Stanford, USA 

The ultimate image guided adaptive radiotherapy to account for anatomic motion 

and deformation will continuously image the patient volume of interest, 

segment the appropriate anatomy, produce an optimal dynamic plan including 

future estimates of patient motion and targeting uncertainties, and deliver 

the dynamic plan. Though far from being integrated into a clinically available 

product, the component tools for each of the steps of this process are relatively 

mature. The status and challenges for integration of the components 

will be described. 

Tomotherapy and IMAT 

53 speaker 

PLANNING OPTIMIZATION ISSUES IN TOMOTHERAPY 

S. Broggi 1 

1 IRCCS SAN RAFFAELE, Medical Physics, Milan, Italy 

Helical Tomotherapy (HT) is a recent modality for intensity modulation delivery 

(IMRT). The radiation beam (6 MV), collimated to a fan beam which is modulated 

with a 64-leaf (nominal width=6.25 mm) binary MLC, is delivered on a 

continuous helix. Intensity modulation is accomplished by varying the aperture 

time of each leaf: the modulation pattern can change with the gantry 

angle and is defined over the course of a "projection", which corresponds 

to a gantry rotation of just 7 ◦ , giving a total of 51 projections per rotation. 

A fully integrated on-board mega-voltage CT (MVCT) system also enables 

image-guided delivery (IGRT). Planning optimisation and delivery are based 

on three specific parameters, able to influence the dose distribution conformation 

and the treatment irradiation time: field width, pitch and modulation 

factor. Inverse planning optimisation is based on an iterative approach and 

the dose calculation uses the convolution/superposition method.A number of 

planning comparison between HT and other irradiation modalities (3DCRT,


conventional IMRT, IMAT, protons) were conducted during last three years. 

The main advantage of HT planning is the excellent coverage and homogeneity 

of the dose distribution inside PTV as well as the ability of concomitantly 

delivering different doses to different target volumes, including very small 

volumes such as overlaps between PTVs and organs at risks. Sharp dose 

gradients may be generated with significant improvements in the sparing of 

organs at risk in many clinical situations. A slightly worsening is obtained for 

HT in the dose gradient reachable along the cranio-caudal direction for critical 

structures not proximal to the target volume, both respect to 3DCRT and conventional 

IMRT In most situations, in-field integral dose does not seem to be 

substantially increased compared to other photon modalities while out-of-field 

integral dose was found to be comparable to conventional IMRT. Treatment 

duration is strongly depending on the parameters applied during optimisation 

(pitch, field width and modulation factor), on the dimension of the PTV and on 

the delivered dose. In our clinical experience, typical average irradiation times 

ranged between 2-3 min/Gy for small PTVs and prostate, and 7-10 min/Gy for 

elongated PTVs (as for cranio-spinal irradiation). 

54 speaker 

THE VARIAN APPROACH TO SINGLE ARC MODULATED THERAPY 

S. Korreman 1 

1 THE FINSEN CENTER - RIGSHOSPITALET, Department of Radiation 

Oncology, Copenhagen, Denmark 

Purpose: Recently, Varian Medical Systems have announced the introduction 

of a new treatment technique, in which dose is delivered over a single 

gantry rotation with variable MLC positions, dose rate and gantry speed. A 

European council consisting of 5 clinics was established to test and evaluate 

the preclinical Eclipse environment for optimization of treatment plans for 

RapidArc delivery. In February 2008, a preclinical installation of the RapidArc 

beam delivery approach was carried out on a Varian Clinac at Rigshospitalet 

in Copenhagen for verification dosimetry purposes. The first clinical 

installations of RapidArc are planned for May 2008. Methods and materials: 

RapidArc plans were generated in the Eclipse preclinical version of the RapidArc 

optimizer for a number of patient cases, including H&N, prostate, cervix, 

anal canal, lung, pancreas, breast, brain and pediatric cases. The RapidArc 

plans were compared to IMRT plans with respect to target coverage, doses 

to organs at risk, doses to other healthy tissues, over-all maximum dose and 

number of monitor units. 20 of the treatment plans were included in the dosimetric 

verification measurements at the Clinac. The plans were delivered 

using a variety of different dosimetric equipment suitable for IMRT; PTW Octavius, 

IBA Dosimetry Matrixx with MultiCube, Scandidos Delta4, the linac 

EPID, radiochromic films and gels. Results: Overall, the RapidArc treatment 

plans gave better or equal sparing of the organs at risk as the IMRT treatment 

plans. The number of monitor units was lower in all cases, by approximately 

30-60%. Target dose homogeneity was more challenging, but was mostly 

comparable to that obtained for IMRT plans. Excellent agreement was observed 

between measured and calculated doses in most cases with gamma 

values above 1 in >95% of measured points. The reproducibility of delivery 

was also very high. Gamma analysis between two consecutive runs of the 

same delivery plan showed gamma values above 1 in none of the measured 

points. Conclusion: RapidArc optimization is very promising, especially regarding 

the potential of reducing the number of monitor units, while providing 

good sparing of organs at risk. The delivery of RapidArc has been verified 

to correspond well with calculated dose distributions for a number of different 

cases. The delivery was very reproducible, and was carried out with high 

stability of the accelerator performance. 

55 speaker 

INITIAL EXPERIENCE WITH ELEKTA VMAT DOSE PLANNING AND 

DELIVERY 

M. Stock 1 , G. Kragl 1 , K. Dieckmann 1 , R. Pötter 1 , D. Georg 1 

1 MEDICAL UNIVERSITY VIENNA, Department of Radiotherapy, Vienna, 

Austria 

Purpose/Objective: To describe and evaluate the clinical experience with 

Volumetric Modulated Arc Therapy (VMAT) implemented by Elekta. Material/Methods: 

A commercial treatment planning system (Ergo++) was used 

to create VMAT-plans for different treatment sites (pelvis, H&N, Brain). Arcs 

and MLC-shapes were defined by the planer semi-automatically. Arc weights 

were optimized by the arc modulation optimization algorithm (AMOA). Following 

parameters were implemented in Ergo++ to account for restrictions in 

beam delivery: min. 0.25MU/ ◦ , max. leaf speed 30 mm/s, gantry 180 ◦ (500 

MU) in 55-80 sec. depending on the energy used. Plans were exported to 

Mosaiq (Vers 1.41B1) and delivered with a Elekta Synergy accelerator (Desktop 

R7.0). During delivery field shape, gantry and collimator angle and dose 

rate changes. Performance parameters like treatment efficiency and deliverability 

were determined. For patient related quality assurance, ionization 

chamber measurements in according points and film measurements in 3 axial 

planes for γ-evaluation were made. For machine related QA ionization 

chamber, films and a 2D ionization chamber array was used. Results: Most 

S 17 

of the tested and applied arc beams were easy to apply, just a small amount 

of beams were not applicable because of restriction mismatch in TPS, R&V or 

linac. The total treatment delivery was in mean 7 min for 3-4 arcs. The mean 

number of MUs per plan were 230. Treated and explored sites, where advantages 

of VMAT can be seen are prostate, brain and H&N tumours. Especially 

when non coplanar arcs can be applied, VMAT shows superior results. 

Measurements with ionization chamber showed acceptable results with deviations 

of less than 3%. The results for the γ-evaluation were acceptable in 

the PTV-region. Some violations of the γ-criteria were seen for the low dose 

area. Conclusion: Initial results demonstrated the feasibility of VMAT, which 

is a promising treatment method for the future with improved efficiency and 

superior dose distributions for different sites. As the pencil beam model implemented 

in the planning software is not state of the art, further improvement 

of dose calculation accuracy can be expected in future versions. More automated 

tools in the VMAT planning process like leaf sequencing would help 

to advance the planning process, especially when adaptive radiotherapy with 

the inclusion of IGRT and online planning is desired. 

56 speaker 

DAILY USE OF MVCT IN TOMOTHERAPY 

A. Vaandering 1 , L. Renard 1 , J. A. Lee 1 , V. Grégoire 1 

1 CLINIQUES UNIVERSITAIRES ST LUC, Radiation Oncology, Brussels, 

Belgium 

Purpose: Helical tomotherapy is a modality of radiation treatment equipped 

with an on-board imaging device (MVCT) which allows for daily patient setup 

verification and correction in the medial-lateral (m-l), cranial-caudal (c-c), 

anterior-posterior (a-p) and transversal angular (roll) direction. In this study, 

we measured the positioning accuracy and evaluated different MVCT protocols 

for brain and head and neck (H&N) tumor patients. 

Materials and methods: The daily set-up errors of 75 H&N patients immobilized 

with 5 fixation points thermoplastic masks and 26 brain patients immobilized 

with 3 fixation points thermoplastic masks were detected by matching 

the MVCT with the treatment plan CT images. This step was accomplished 

automatically by the system’s software (automatic deviations) and manually 

by the nurses (accepted deviations). Systematic and random errors were 

then analyzed on a patient and population basis. Moreover, 2 MVCT protocols 

were retrospectively evaluated in which MVCTs are either realized during 

the treatment’s first five fractions or on alternate weeks. The systematic deviations 

calculated during the prior "MVCT" week were automatically corrected 

for during the "non-MVCT" days. The effect of these protocols on dose distributions 

is currently being analyzed. 

Results: The accepted systematic (random) deviations reached 1.7mm 

(1.4mm), 1.6mm (1.5mm), 1.5mm (1.5mm) and 0.5 ◦ (0.6 ◦ ) for H&N cancer 

patients and reached 1.7mm (0.91mm), 1.7mm (1.1mm), 1.1mm (0.8mm) 

and 1.1 ◦ (0.7 ◦ ) brain cancer patients in the m-l, c-c, a-p and roll direction, respectively 

. A t-test detected statistical but not clinically significant differences 

between the accepted and automatic deviations. Both MVCT protocols do result 

in similar residual deviations, but the CTV-PTV margins that would need 

to exist if these protocols were to be applied are inferior for the alternate week 

protocol. The effect of these observations on dose distribution is being evaluated. 

Conclusion: The systematic and random accepted deviations are comparable 

to published studies. There existed no clinical difference between the 

accepted and automatic deviations but manual refinements do have their usefulness. 

The alternate week MVCT protocol seems to be a correct formula 

to adopt in order to diminish the frequency of pre-treatment MVCTs. However, 

the clinical relevance of these observations can be discussed and their 

effects on dose distributions are currently being studied.


Use of PET/CT for radiation treatment planning 

57 speaker 

USE OF PET-CT IN RADIOTHERAPY PLANNING 

L. O’Neill 1 

1 ST LUKE’S HOSPITAL, Dublin, Ireland Republic of 


58 speaker 

THERAPY PET-CT SCANNING - THE NURSING POINT OF VIEW 

E. Abrahamsson 1 

1 RIGSHOSPITALET, UNIVERSITY HOSPITAL OF COPENHAGEN, Department 

of Clinical Physiology, PET Cyclotron Unit, Copenhagen, Denmark 

The use of PET/CT scanning has dramatically increased over the last few 

years. PET/CT scanning with FDG is today an important imaging modality in 

diagnosing, staging, follow-up, localizing recurrence and for radiation therapy 

planning. By using the PET tracer FDG ( fluordeoxyglucose) it is possible 

to define the metabolic activity of the tumour and with the CT scan to define 

the anatomical details and tissue homogeneities. With the combined PET/CT 

for therapy planning it is therefore possible to define the target volume and 

the risk organs, tailor the radiation treatment and hopefully reduce the side 

effects. The therapy PET/CT is especially valuable for head and neck cancer, 

esophageal- and cardia cancer, lung cancer, cervix cancer, anal cancer 

and lymphoma. From the patient’s point of view the dual PET/CT imaging 

is more comfortable because just one scan session is necessary. Performing 

a therapy PET/CT scan is a complex session and demands trained staff. 

In our hospital we have a very successful collaboration with multidisciplinary 

teams from the PET department and the Radiotherapydepartment, both contributing 

with professional trained staff. Overall patient care is very important 

and a well-structured day for the planning session must be organized. The 

planning day includes a chain of different functions and communication flow, 

and the patient will meet a different person for each function, each an expert 

on their domain. The first step at arriving in the treatment unit is making 

an immobilization device and establishing a treatment chart. The patient will 

have a talk with one of the responsible nurses at the treatment unit, who informs 

the patient about the course of events for the treatment. The standard 

patient preparation for a PET/CT study is also used for a therapy PET/CT. 

To achieve optimal PET imaging data and to avoid artefacts and pitfalls, it is 

very important to follow the correct preparations, e.g. be fasting six hours 

before FDG injection, be well hydrated, avoid exercise and remember to keep 

warm, in order to avoid uptake in muscles and brown fat tissue. Patient positioning 

in the PET/CT scanner follows the same principles as for all therapy 

planning; comfortable for the patient, easily reproduced and secure. We use 

an external LAP-laser system for positioning and markings of the ISO-centre 

and reference points. The major subject when preparing and performing the 

therapy PET/CT scan is the radiation burden to the involved personnel. The 

FDG -tracer discharges photons with an energy of 511 keV and great penetrating 

ability. It is therefore important that all information handlings, moulding 

and other preparations have to be done before the tracer injection. The time 

with the injected patient should be minimised and the radiation burden should 

be shared between several personnel, who should be experienced and well 

trained in handling radioactivity. 

References: 

1. Grire V, Haustermans, K, Geets X, et al. PET-based treatment planning in 

radiotherapy: A new standard? Eur J Nucl Med 2007; 48:6877. 

2. Borgwardt L, et al. Practical use and implementation of PET in children in 

a hospital PET centre. Eur J Nucl Med Mol Imaging (2003) 30:1389-1397 

3. Ava Bixler, Greg Springer, Richard Lovas. Practical Aspects of Radiation 

Safety for Using Fluorine-18. J Nucl Med Technol 1999; 27:14-16 

59 speaker 

4D GATED PET/CT: ACQUISITION, PROCESSING AND THERAPEU- 

TIC APPLICATIONS 

S. Cola 1 

1 ARCISPEDALE S. MARIA NUOVA, Department of Nuclear Medicine, Reggio 

Emilia, Italy 

Purpose/objective. 4D PET-CT imaging is becoming increasingly available for 

radiotherapy treatment planning. The possibility to personalize the margins 

around the tumor will allow improved local control and reduced treatment toxicity. 

The aim of this study was to evaluate the impact of respiratory-gated 

PET-CT imaging on lung cancer patient treatment planning.Material/methods 

We use a new generation PET/CT scanner 16 slice linked to a gating respiratory 

acquisition system composed of an infrared video camera and remote 

computer (workstation RPM). The patient is injected intravenously with 255- 

370 MBq of 18F 2-fluoro-2-deoxy-D-gluose (18FDG), after about one hour he 

is setup on the rigid bed in the radiotherapy treatment position. The patient’s 

respiratory motion is monitored by the infrared video camera, tracking external 

markers placed in the point of maximum vertical excursion.Results For the 

patients, 4D PET-CT derived patient specific margin led to a reduction of tumor 

margin and thus significantly reduced the lung toxicity.The gated studies 

allowed moreover to identify the patients who might benefit from respiratorygated 

radiation treatment.Conclusions 4D PET-CT provides information on 

extent and trajectory of lesion motion for a more precise dose delivery, with 

an increase of tumor dose homogeneity and a reduction of the dose to critical 

structures. 

Presidential Symposium 

60 speaker 

GENOME WIDE DISEASE ASSOCIATION STUDIES 

V. Kristensen 1 , A. L. Borresen-Dale 1 

1 INSTITUTE FOR CANCER RESEARCH AND INSTITUTE FOR CLINICAL 

EPIDEMIOLOGY, Faculty of Medicine, University of Oslo, Oslo, Norway 

Recent developments in whole genome Single Nucleotide Polymorphism 

(SNP) analysis have spurred a number of Genome-Wide Association Studies 

(GWAS) in breast, prostate, and up-coming testicular and bowel cancer cancer 

(1,2,3). Until now the genetic variants that have been revealed by these 

studies are responsible for comparatively small increases in relative risk of 

disease and it is unlikely that highly predictive genetic variants will emerge 

from subsequent studies, even if one takes into consideration the multistage 

design of GWAS studies that is aimed at "amplifying" the hereditary effect by 

using individuals with a highly familial component of the disease as a starting 

point. At present the goal is to interrogate the data concentrating on clinical 

and molecular subtypes for each of the diseases studied, first identifying 

discreet molecular and clinical subtypes for each disease and subsequently 

improving data analysis including probability models, pattern recognition and 

Bayesian neuronal networking models. To improve the reliability and accuracy 

of the molecular classification by expression profiles, we need to identify 

the role an individual’s genotype (SNPs, CNVs) and exposure (eg hormones) 

has on these profiles. Recently, GWAS analysis of BC has revealed SNPs 

in 5 novel genes associated to susceptibility. Should the probability of developing 

a given subclass of breast cancer be genetically determined, we might 

expect to find that the newly discovered susceptibility genes are differentially 

expressed in the various tumor subclasses, and that their transcription is regulated 

in cis by SNPs within them. With this in mind, we retrieved the mRNA 

expression data of these 5 genes from 112 breast tumors representing all 

5 subclasses, and significantly different mRNA levels between the subtypes 

were found for all the 5 genes by ANOVA analysis (4). One known strong factor 

underlying the subclassification is the estrogen receptor (ER). We have 

previously reported that the expression of a set of nine mRNA transcripts 

of members of the oestradiol metabolic and signalling pathways, including 

CYP19 (aromatase), was significantly different in the five molecular subtypes 

(5). We have identified a SNP in the 30-untranslated area of CYP19 mRNA 

to be associated to higher mRNA levels and tumor size in locally advanced 

breast cancers (stage III/IV) (6). The distribution of the different alleles of this 

SNP is significantly different in the five molecular subtypes. This illustrates the 

necessity to conduct stratified SNP-disease association studies (7). Stratification 

of patients by their molecular subtypes may give much more power 

to the classical case control studies, and genes of no or borderline overall 

significance may be highly penetrant for certain subclasses, and therefore 

identifiable. 

1. Easton DF, Pooley KA, Dunning AM, Pharoah PD, Thompson D,Ballinger 

DG, Luben R, et al.:Genome-wide association study identifies novel breast 

cancer susceptibility loci. Nature 2007, 447:1087-1093. 

2. Hunter DJ, Kraft P, Jacobs KB, Cox DG, Yeager M, Hankinson SE, Wacholder 

S, Wang Z, Welch R, Hutchinson A, et al.: A genome-wide association 

study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal 

breast cancer. Nat Genet 2007, 39:870-874. 

3. Stacey SN, Manolescu A, Sulem P, Rafnar T, Gudmundsson J,Gudjonsson 

SA, Masson G, Jakobsdottir M, Thorlacius S, Helgason A, et al.: Common 

variants on chromosomes 2q35 and 16q12 confer susceptibility to estrogen 

receptor-positive breast cancer. Nat. Genet 2007, in press. 

4. Kristensen, V.N., Harada, N., Yoshimura, N., Haraldsen, E.,Lonning, P.E., 

Erikstein, B., Karesen, R., Kristensen, T.,Brresen-Dale, 2000. Genetic variants 

of CYP19(aromatase) and breast cancer risk. Oncogene 19, 13291333. 

5. Kristensen, V.N., Srlie, T., Geisler, J., Langerd, A.,Yoshimura, N., Ka ◦ resen, 

R., Harada, N., Lnning, P.E., Brresen-Dale, A.L., 2005. Gene expression 

profiling of breast cancer in relation to estrogen receptor status and estrogen 

metabolizing enzymes: clinical implications. Clin. Cancer Res. 11, 878883. 

6. Nordgard, S.H., Johansen, F.E., Aln G.I., Naume, B., Brresen-Dale, A.L., 

Kristensen, V.N., 2007. Genes harbouring susceptibility SNPs are differentially 

expressed in the breast cancer subtypes. Breast Cancer Res. 9, 113. 

7. Vessela N. Kristensen, Brresen-Dale, A.-L., 2008 SNPs associated with 

molecular subtypes of breast cancer: On the usefulness of stratified Genomewide 

Association Studies (GWAS) in the identification of novel susceptibility 

loci, Molecular Oncology (2008), doi:10.1016/j.molonc.2008.02.003

MONDAY, SEPTEMBER 15, 2008 PROFFERED PAPER 

61 speaker 

NANO PARTICLES IN RADIATION ONCOLOGY 

K. A. Vallis 1 

1 UNIVERSITY OF OXFORD, Radiation Oncology and Biology, Oxford, United 

Kingdom 

Nanobiotechnology is a rapidly evolving field with the potential to impact the 

practice of radiation oncology. Several types of nanoparticle are being evaluated 

as vehicles for the targeted transport of contrast agents, cytotoxics 

and radioisotopes to tumours. Some nanoscale drug delivery systems, such 

as liposomes, have been in clinical use for some time. More recently innovations 

such as quantum dots, nanoshells, block co-polymer micelles and 

carbon nanotubes have been developed. The encapsulation capacity, drug 

release profile and performance of nanoparticles vary with their size and with 

their chemical and physical nature. Nanoparticles can be designed to bind to 

specific cellular compartments such as the cell membrane, cytoplasmic and 

nuclear receptors or even to components of the microenvironment. Generally, 

nanoparticles present an extensive surface area and can therefore carry large 

payloads, improving the chance of cancer detection or of delivering cytotoxic 

quantities of anticancer agent, compared to conventional pharmaceuticals. 

Nanoparticles that are modified by the addition of several different antibodies, 

capable of recognizing an array of epitopes, may be used to overcome 

the problem of target heterogeneity within a tumour. Despite the potential 

benefits of nanoparticles, concerns about their toxicity, pharmacokinetic properties 

and stability remain. In this session, recent developments in the design 

of nanoparticles and related platforms will be reviewed. The potential diagnostic 

and therapeutic applications of nanoparticles in radiation oncology will 

be considered. 

62 speaker 

A COMPACT LINAC FOR INTENSITY MODULATED PROTON 

THERAPY BASED ON A DIELECTRIC WALL ACCELERATOR 

G. J. Caporaso 1 , T. Mackie 2 , S. Sampayan 1 , Y. J. Chen 1 , D. Blackfield 1 , 

J. Harris 1 , S. Hawkins 1 , C. Holmes 1 , S. Nelson 1 , A. Paul 1 , B. Poole 1 , M. 

Rhodes 1 , D. Sanders 1 , J. Sullivan 1 , L. Wang 1 , J. Watson 1 , P. Reckwerdt 

2 , R. Schmidt 2 , D. Pearson 2 , R. Flynn 3 , D. Matthews 4 , J. Purdy 4 

1 

LAWRENCE LIVERMORE NATIONAL LABORATORY UNIVERSITY, Livermore 

CA, USA 

2 

TOMOTHERAPY INCORPORATED, Madison, WI, USA 

3 

UNIVERSITY OF WISCONSIN, MADISON, Madison WI, USA 

4 

UNIVERSITY OF CALIFORNIA, DAVIS, Sacramento, USA 

A novel compact CT-guided intensity modulated proton radiotherapy (IMPT) 

system is described. The system is being designed to deliver fast IMPT so 

that larger target volumes and motion management can be accomplished. 

The system will be ideal for large and complex target volumes in young patients.The 

basis of the design is the dielectric wall accelerator (DWA) system 

being developed at the Lawrence Livermore National Laboratory (LLNL). The 

DWA uses fast switched high voltage transmission lines to generate pulsed 

electric fields on the inside of a high gradient insulating (HGI) acceleration 

tube. High electric field gradients are achieved by the use of alternating insulators 

and conductors and short pulse times. The system will produce individual 

pulses that can be varied in intensity, energy and spot width. The 

IMPT planning system will optimize delivery characteristics. The system will 

be capable of being sited in a conventional linac vault and provide intensity 

modulated rotational therapy. Feasibility tests of an optimization system for 

selecting the position, energy, intensity and spot size for a collection of spots 

comprising the treatment are underway. A prototype is being designed and 

concept designs of the envelope and environmental needs of the unit are beginning. 

The status of the developmental new technologies that make the 

compact system possible will be reviewed. These include, high gradient vacuum 

insulators, solid dielectric materials, SiC photoconductive switches and 

compact proton sources. Conflict of Interest: Some of the authors have financial 

interest in TomoTherapy, Inc., which has licensed the DWA technology 

from LLNL. *Patents Pending. Lawrence Livermore National Laboratory 

is operated by Lawrence Livermore National Security, LLC, for the U.S. Department 

of Energy, National Nuclear Security Administration under Contract 

DE-AC52-07NA27344. 


Phase III randomised trials 

63 oral 

S 19 

VAGINAL BRACHYTHERAPY VERSUS EXTERNAL BEAM PELVIC 

RADIOTHERAPY FOR HIGH-INTERMEDIATE RISK ENDOMETRIAL 

CANCER: RESULTS OF THE RANDOMIZED PORTEC-2 TRIAL. 

R. Nout 1 , H. Putter 2 , I. Jürgenliemk-Schulz 3 , J. Jobsen 4 , L. Lutgens 5 , E. 

van der Steen-Banasik 6 , J. W. Mens 7 , A. Slot 8 , M. Stenfert Kroese 9 , B. 

van Bunningen 10 , V. Smit 11 , P. van den Tol 12 , C. Creutzberg 1 

1 

LUMC, Clinical Oncology, Leiden, Netherlands 

2 

LUMC, Department of Biostatistics, Leiden, Netherlands 

3 

UMCU, Radiotherapy, Utrecht, Netherlands 

4 

MEDISCH SPECTRUM TWENTE, Radiotherapy, Enschede, Netherlands 

5 

MAASTRO, Radiation Oncology, Maastricht, Netherlands 

6 

ARTI, Radiotherapy, Arnhem, Netherlands 

7 

ERASMUS MC, Radiotherapy, Rotterdam, Netherlands 

8 

RIF, Radiotherapy, Leeuwarden, Netherlands 

9 

RADIOTHERAPY INSTITUTE STEDENDRIEHOEK, Radiotherapy, Deventer, 

Netherlands 

10 

NETHERLANDS CANCER INSITUTE, Radiotherapy, Amsterdam, Netherlands 

11 

LUMC, Pathology, Leiden, Netherlands 

12 

LUMC, IKW-datacenter, Leiden, Netherlands 

Purpose: Postoperative pelvic external beam radiotherapy (EBRT) reduces 

the risk of pelvic recurrence for patients with stage I endometrial carcinoma 

(EC), but without a survival benefit. In the first PORTEC-trial, the 5-year risk 

of pelvic recurrence for patients with high-intermediate risk features was 19% 

without further treatment, as compared to 5% after EBRT. The majority of 

recurrences were located in the upper vagina. Phase II trials have suggested 

vaginal brachytherapy (VBT) to be as effective as EBRT in reducing vaginal 

relapse, but with less morbidity. Two-year quality of life results have shown a 

benefit for VBT: EBRT patients reported significantly more bowel symptoms, 

resulting in limitation of daily activities. PORTEC-2 is the first randomized 

trial comparing the efficacy of VBT and EBRT to determine which treatment 

provides local control with least morbidity and best quality of life. 

Materials: The PORTEC-2 trial was a multicenter randomized trial. After 

surgery, patients were randomly allocated (1:1) to pelvic EBRT (46 Gy in 23 

fractions) or VBT (21 Gy HDR in 3 fractions, or 30 Gy LDR). Eligible patients 

had a high-intermediate risk EC, defined as: age at least 60 and stage 1C 

grade 1-2 or stage 1B grade 3; any age and stage 2A grade 1-2 or grade 3 

with < 50% myometrial invasion. Stratification was done for stage, treatment 

center, VBT dose rate, and age. Primary endpoint was vaginal relapse rate 

(VRR).The aim was to estimate the difference in VRR with sufficient precision 

(SE 80%) for detecting a difference of 6% (8% vs 2%) in VRR between 

both arms (one-sided). Secondary endpoints were survival (OS), quality of 

life, toxicity, and overall pelvic recurrence. VRR and pelvic recurrence were 

compared using competing risk analysis; OS were compared using a log-rank 

test. 

Results: A total of 427 patients were randomized (214 to EBRT and 213 to 

VBT). Current median follow-up is 2 years and 9 months. Analysis of the 

primary endpoint shows a low number of vaginal relapses, with a SE of the 

difference between the VRR in both treatment arms

S 20 PROFFERED PAPER MONDAY, SEPTEMBER 15, 2008 

ment of Urology, Exeter, United Kingdom 

5 

SUSSEX CANCER CENTRE, Department of Radiotherapy, Brighton, United 

Kingdom 

6 

CHELTENHAM GENERAL HOSPITAL, Glocestershire Oncology Centre, 

Cheltenham, United Kingdom 

7 

SOUTH DEVON HEALTHCARE TRUST, Department of Radiotherapy, 

Torquay, United Kingdom 

Purpose: Radiotherapy has been used as alternative to radical cystectomy 

for the management of muscle invasive bladder cancer. Important limitations 

to its use are a). the probability of attaining and maintaining local tumour 

control and b). the risk of late bladder toxicity. The BC2001 trial was set up 

to address whether the use of concomitant chemotherapy could improve loco 

regional control and whether radiotherapy volume modification could reduce 

late toxicity without detriment to tumour control. This is the first report of this 

trial focusing on the radiotherapy volume randomisation. 

Materials: BC2001 is a multicentre randomised phase III trial utilising a 2x2 

design. Patients have been randomised to one or both of two randomisations. 

The first randomisation was between radiotherapy alone or radiotherapy with 

5Fluoruracil (500mg/m2 daily for five days as continuous infusion weeks one 

and four) and mitomycin C day 1 of radiotherapy only. The second randomisation 

was between radiotherapy to the tumour and whole bladder (sRT) with 

1.5cm margin versus a reduced volume treatment (rvRT). In rvRT, the tumour 

+1.5cm margin was treated to 100+/-5% target dose whilst the remaining 

bladder received 80% of the target dose delivered either by a two-phase approach 

or a concomitant boost technique. All patients were CT planned on an 

empty bladder using 3or4 fields. Conformal fields were allowed but not mandated. 

Patients could receive either 55Gy in 20f or 64Gy in 32f. The primary 

endpoint for the radiotherapy was the late toxicity at one year as assessed 

by RTOG scores. The trial was originally designed to recruit 480 patients to 

have 86% power to detect a 15% reduction in RTOG grade 3-4 toxicity from 

40% to 25%. The trial was closed before full accrual due to slow recruitment 

in September 2006. At that time 212 patients had been recruited giving an 

estimated power of 73% a two sided alpha of 5% to detect an improvement in 

RTOG grade toxicity from 40% to 20%. Analysis will be by intention to treat. 

Results: At the time of trial closure 220 patients had been recruited into the 

stRT vs. rvRT comparison, 109 patients to sRT and 111 to rvRT with 64 of 

these patients were randomised to receive chemo-RT. The median age was 

73 years, 80% were Male, WHO performance status (0) 57%, (1) 37%, (2) 

6%. Initial summary analysis, for the purposes of this abstract, show that in 

the rvRT arm around 72% patients received two-phase treatment, 26% by 

concomitant boost and 2% patients receiving sRT (protocol deviation). The 

median follow up is currently over 24 months. CTC Grade 3 or 4 acute toxicity 

was reported in 20% of stRT patients (n=105) and 25% of rvRT patients 

(n=106). RTOG grade 3/4 Late GU toxicity was reported in 26/89 patients 

(with evaluable data) (13 stRT, 13rvRt) and late GI toxicity in 8/53 patients 

(5stRT, 3rvRT). 

Conclusions: Full clinical trial analysis of the randomised results will be undertaken 

in May 2008 and will be presented at the ESTRO meeting. 

65 oral 

INDUCTION CHEMOTHERAPY (ICT) AND DOSE INTENSIFICATION 

OF THE RADIATION BOOST IN LOCALLY ADVANCED ANAL 

CANAL CARCINOMA (LAACC): DEFINITIVE ANALYSIS OF THE 

INTERGROUP ACCORD 03 TRIAL (FÉDÉRATION NATIONALE 

DES CENTRES DE LUTTE CONTRE LE CANCER ? FONDATION 

FRANÇAISE DE CANCÉROLOGIE DIGESTIVE) 

D. Peiffert 1 , J. P. Gerard 2 , M. Ducreux 3 , C. Lemanski 4 , E. Francois 5 , M. 

Giovannini 6 , F. Cvitkovic 7 , X. Mirabel 8 , O. Bouché 9 

1 

CENTRE ALEXIS VAUTRIN, Radiation Oncology, Vandoeuvre-lès-Nancy, 

France 

2 

CENTRE ANTOINE LACASSAGNE, Radiation Oncology, Nice, France 

3 

INSTITUT GUSTAVE ROUSSY, Department of Gastro-Enterology, Villejuif, 

France 

4 

CENTRE VAL D’AURELLE, Radiation Oncology, Montpellier, France 

5 

CENTRE ANTOINE LACASSAGNE, Medical Oncology, Nice, France 

6 

INSTITUT PAOLI-CALMETTES, Department of Gastro-Enterology, Marseille, 

France 

7 

CENTRE RENÉ HUGUENIN, Medical Oncology, St Cloud, France 

8 

CENTRE OSCAR LAMBRET, Radiation Oncology, Lille, France 

9 

CHU ROBERT DEBRÉ, Department of Gastro-Enterology, Reims, France 

Purpose: Combined radiochemotherapy is the standard treatment of LAACC. 

The addition of an ICT (Ann Oncol 2001;12:397) and of a higher dose of 

irradiation boost (HDRT) are studied in a 4 arms trial (A= ICT, B=ICT+HDRT, 

C= Reference= Pelvic RT: 45Gy in 25 fractions with 2 cycles of 5FU-CDDP 

W1 and W5 and a boost of 15 Gy, D= HDRT). The aim of the study (closed in 

March 2005) was to compare the results in terms of Colostomy free survival 

(CFS). 

Materials: 307pts included by 20 institutes in 74 months were analysed. The 

mean age was 59 y. [range 31-81], the sex ratio was 6/1. All the LAACC were 

SCC histologic type. There were 10 T1, 130 T2, 106 T3, 53 T4, 8 TX, 180 

N0, 53 N1, 63 N2-3, 11 NX. The T size was < 4 cm in 70 pts and ≥ 4 cm in 

212 pts, ND 25 pts. The 4 arms were well balanced concerning the sex ratio, 

age, stage, T size, differentiation. 

Results: One violation of the protocol was noticed (metastatic disease). The 

tolerance to the treatment was similar in the 4 arms (A: 4 toxic deaths, B=2, 

C=2, D +1). 4 pts did not receive the irradiation boost. The compliance to 

the treatment was: 99% for ICT, 100% for pelvic RT-CT (median dose= 45 

Gy), and 96% for the boost. The tumour complete (+ partial) responses at 2 

months were: A: 78% (+18%), B: 86% (+13%), C: = 74% (+21%), D: = 74 

% (+22%), (NS). The median and mean follow-up were 43 months [range 1 - 

94]. Overall failures ( 28%): arm A: 28%, arm B: 21.%, arm C: 30%, arm D: 

30%. The actuarial results at 3 years were: Local control (88%): arm A: 80%, 

B: 96%, C: 90 %, D: 87%. Event free survival (71%): arm A: 70%, B: 78%, 

C: 67%, D: 68%. Overall survival was 78% at 3 Y (73% at 5 y). The causes 

of the 74 deaths were the cancer in 50 pts (A: 15 pts, B: 8 pt, C: 11 pts, D: 

16 pts). The colostomy free survival was 83% at 3 years: A: 83%, B: 85%, 

C: 86%, D: 80%. The specific survival was 84 % at 3 y: A=79%, B=88,5%, 

C=89%, D=79%. 

Conclusions: The results will be analysed to better understand the high rate 

of local control for improvement of the colostomy free results 

DNA-repair and signal transduction 

66 oral 

BASE EXCISION REPAIR DEFICIENT CELLS RELY ON HOMOLO- 

GOUS RECOMBINATION FOR SURVIVAL AFTER RADIATION: A 

POTENTIAL NEW STRATEGY FOR TUMOR-SPECIFIC RADIOSEN- 

SITIZATION 

C. Vens 1 , S. Neijenhuis 1 , M. Verwijs-Janssen 1 , L. van den Broek 1 , M. 

Pourghiasian 1 , B. Adrian 1 

1 THE NETHERLANDS CANCER INSTITUTE, Department of Experimental 

Therapy, Amsterdam, Netherlands 

Purpose: To elucidate DNA repair backup pathways in response to radiation 

in tumor cells harboring mutations in genes of the base excision repair (BER) 

pathway. The long term goal is to exploit this knowledge for tumor specific 

radiosensitization. 

Materials: The roles of BER and homologous recombination (HR) were assessed 

using cells deficient in DNA polymerase beta (polb), or expressing 

a truncated form of polb, or deficient in rad51C. Survival was assessed by 

colony formation. Homologous recombination was analyzed by RAD51 foci 

formation. DSB induction was monitored by chromosome and chromatid 

aberrations. 

Results: DNA polymerase beta (polb) has been identified as a crucial enzyme 

in BER and single strand break repair (SSBR). We have previously 

shown that expression of truncated polb (polbDN) resulted in radiosensitization, 

confirming polb’s critical role in repair of IR induced DNA damage. 

We hypothesized that the dominant negative action of the truncated polb resulted 

from the capacity to block alternative BER sub-pathways at lesions and 

repair intermediates otherwise dealt with by the wildtype enzyme. We speculated 

that the increased cytotoxicity when expressing polbDN results from 

the formation of additional DSBs from unrepaired BER/SSBR intermediates. 

Indeed, inhibition of BER after IR by the expression of the polbDN showed 

an increased induction of chromosome aberrations, thus demonstrating the 

formation of additional secondary DSBs. These resulted partly from SSBs 

or BER intermediates encountering a replication fork as underlined by the 

increased formation of chromatid-type of aberrations. Since replication associated 

secondary DSBs have been reported to be repaired by HR dependent 

processes, we expected repair of the polbDN induced secondary DSBs to rely 

on this DSB repair pathway as backup. To test this, we expressed polbDN in 

HR-proficient and deficient cells. A marked increase in polbDN-induced radiosensitization 

in the HR-deficient cells compared to the HR-proficient cells 

confirmed our hypothesis. HR dependence was further demonstrated by increased 

rad51 foci formation after IR in polbDN expressing cells. 

Conclusions: Our studies reveal an increased dependence on HR after irradiation 

in cells impaired in BER. These findings could be translated into a 

tumor-specific radiosensitization strategy in which tumors impaired in BER, 

i.e. expressing aberrant polb, are specifically radiosensitized with an HR 

inhibitor. Low inhibitor doses could be used, which are non-sensitizing in 

normal cells. We provide proof of principle by showing increased radiosensitization 

in polbDN expressing cells by caffeine, which is known to inhibit HR 

dependent processes after IR. Since a considerable proportion of tumors express 

aberrant or truncated polb, future studies are directed at exploiting the 

HR-dependence of BER impaired tumors for potential clinical application.


67 oral 

SENSING OF DNA-DSBS UNDER CONTINUAL HYPOXIA 

R. Bristow 1 , R. Kumareswaran 1 , F. Jalali 1 , N. Chan 1 

1 PRINCESS MARGARET HOSPITAL AND UNIVERSITY OF TORONTO, Applied 

Molecular Oncology, Ontario Cancer Institute, Toronto, Canada 

Purpose: Incorrectly repaired DNA double strand breaks (DNA-dsbs) can 

result in genomic instability, tumour progression and altered sensitivity to radiotherapy. 

Intracellular hypoxia may also give rise to genetic instability, although 

little is known about the effect of hypoxia on DNA-dsb sensing. The 

initial sensing of DNA-dsbs following ionizing radiation (IR) is mediated by the 

MRE11-ATM complex and the susequent phosphorylation of gammaH2AX 

with subsequent recruitment of MDC1, 53BP-1 and DNA-dsb reapir proteins. 

We therefore tested whether the sensing of DNA-dsbs and chromatin biology 

is decreased in cells irradiated under,and kept under, continual hypoxic or 

anoxic conditions. 

Materials: To test this hypothesis, we used normal diploid fibroblast strains, 

GM05757, synchronized in G0-G1 to preclude DNA replication as a source of 

DNA repair foci. The cells were pre-treated with 0.2% O2 (hypoxia), 0.0% O2 

(anoxia) or 21% O2 (normoxia) for 16 hours and then irradiated and kept under 

hypoxic/ anoxic/ normoxic conditions for another 24 hours. The biomarkers 

gammaH2AX, MRE11, 53BP-, ATMSre1981 and the MRN comples was 

tracked using quantitative immunofluorescent microscopy to score intranuclear 

foci. We also completed COMET and clonogenic assays for similarly 

treated cells. 

Results: We observed an expected 2 to 3 fold decrease in initial number 

of gammaH2AX foci at 30 minutes following 2 or 5 Gy post-IR under hypoxia 

and anoxia; consistent with the OER. However, we observed an increase 

in the relative ATM-dependent residual gammaH2AX foci at times between 

4 and 24 hours post-IR under continual hypoxia. 53BP-1 and ATM foci 

were also elevated. These residual foci corresponded to increased residual 

DNA-dsbs based on neutral COMET assays and were not related to altered 

phosphatase levels (e.g. PP2A). Of interest, these residual DNA breaks in 

G0-G1 did not lead to increased cell kill following clongenic assays, suggesting 

that these breaks can be repaired when cells are released into S and 

the G2M phases post-2Gy. Current experiments are testing whether there 

is decreased fidelity of repair and altered chromatin structure following irradiaiton 

under hypoxia with clinically-relevant doses of IR in NHEJ-proficient and 

NHEJ-deficient cells. 

Conclusions: Hypoxic cells may have an altered ability to sense and repair 

DNA-dsbs in G0-G1. The hypoxic and anoxic cells also show abnormal 

chroamtin structure. Our findings are consistent with aberrant DNA-dsb sensing 

and repair under hypoxia as a potential factor in genetic instability and may 

relate to the role of hypoxia in tumor progression. Supported by a Terry Fox 

Hypoxia Project Program Grant and CCS Career Award to RGB. 

68 oral 

RADIATION SURVIVAL AND REPAIR OF RADIOGENIC DNA DOUBLE 

STRAND BREAKS: A COMPARISON BETWEEN CELL GROWTH AS 

MONOLAYER OR THREE-DIMENSIONALLY 

N. Cordes 1 , K. Storch 1 

1 ONCORAY, Dresden, Germany 

Purpose: Adhesion to extracellular matrix (ECM) proteins influences cell survival 

after exposure to ionizing radiation. DNA repair of radiation-induced 

DNA lesions might meet distinct molecular regulatory processes on the basis 

of differential interactions of cells with ECM under two- versus threedimensional 

growth controlling cell shape and chromatin organization. The 

aim of this study was to evaluate the repair of radiation-induced DNA double 

strand breaks (DSBs) under three-dimensional (3D) cell culture conditions in 

comparison to traditional two-dimensional (2D) cell culture. 

Materials: The human lung carcinoma cell line A549 was cultivated with 

laminin-rich extracellular matrix (lrECM) under 2D and 3D conditions. In addition 

to clonogenic radiation survival (0-6 Gy), the number of DNA DSBs 

was determined using the foci assay (gammaH2AX-S139 plus p53BP1). Radiation 

induced phosphorylation of ATM-S1981 and gammaH2AX-S139, expression 

of p21, acetylation of histone H3 and cell cycling were analyzed 

in irradiated cells by Western Blotting or fluorescence-activated cell sorting 

(BrdU plus PI), respectively. 

Results: Clonogenic radiation survival was significantly (p < 0.05) increased 

in A549 cells cultivated in 3D as compared to 2D. Furthermore, irradiated 

cells grown in 3D had significantly less (p < 0.05) residual DNA DSBs than in 

2D. The number of residual DSBs and the cellular survival correlated with r2 

= 0.9327 (p < 0.0001). In comparison to 2D, the number of DSBs was significantly 

(p < 0.001) lower in 3D within the first six hours of DNA repair. In parallel, 

radiation-induced phosphorylation of ATM-S1981 and gammaH2AX-S139 

was also reduced under 3D conditions. Most interestingly, three-dimensional 

growth prevented a radiation-induced G2 phase block, which was characteristically 

executed in 2D cultivated cells. A missing radiation-induced p21 

induction further underscored this difference in cell cycling. Associated with 

chromatin condensation, histone H3 was clearly less acetylated in 3D in contrast 

to 2D. 

S 21 

Conclusions: The data indicate that cells irradiated under 3D cell culture 

conditions show an altered radiation-induced DNA repair response than 2D 

cell culture, which can be linked to improved clonogenic radiation survival. 

Future studies in 3D will elucidate the impact of extracellular matrix for chromatin 

structure and DNA repair. 

69 oral 

CAVEOLIN-1 CONTRIBUTES TO REGULATION OF RADIATION 

SURVIVAL VIA THE BETA1 INTEGRIN/AKT SIGNALING AXIS 

S. Hehlgans 1 , I. Eke 1 , N. Cordes 1 

1 ONCORAY, Dresden, Germany 

Purpose: Caveolin-1 serves in endo-/exocytosis as well as in mutual and 

cooperative signaling from integrins and receptor-tyrosine kinases, both of 

which putatively contribute to radiation and chemoresistance of tumors. Using 

a three-dimensional (3D) cell culture model, this study was performed 

to evaluate the distinct role of Caveolin-1 in radiation survival of pancreatic 

tumor cell lines and its interactions with beta1 integrin. 

Materials: Pancreatic tumor cell lines (PATU-8902, MiaPaCa2, Panc1) were 

stably transfected with a Caveolin-1 expression vector (plus/minus GFP) or 

empty vector or transiently with Caveolin-1 siRNA. Upon irradiation (0-6 Gy, 

X-rays), 3D laminin-rich extracellular matrix (3D lrECM) cell cultures were 

subjected to 3D clonogenic assays, Western blotting (Caveolin-1, beta1 integrin, 

ILK, PINCH-1, FAK, Paxillin, p130Cas, AKT, GSK3beta, Rac), immunoprecipitation 

and intracellular tracking of Caveolin-1-GFP and fluorochromelabeled 

monoclonal anti-beta1 integrin antibodies. 

Results: Overexpression of Caveolin-1 improves clonogenic radiation survival 

of tested cell lines while siRNA-mediated Caveolin-1 knockdown resulted 

in significantly (p


Conclusions: These data indicated that EGFR-ligand-induced AKT phosphorylation 

is independent of erbB1/erbB2 heterodimerization but dependent 

on erbB1 homodimerization. However, IR-induced AKT phosphrylation is 

dependent on erbB1/erbB2 heterodimerization. Moreover, IR-induced AKT 

phosphorylation seems to be independent of erbB2 kinase activity. AcknowledgementThis 

work was supported by grant from the Deutsche Forschungsgemeinschaft 

(DFG PAK 190, Ro527/5-1 

71 oral 

RADIOTHERAPY FRACTION SIZE SENSITIVITY MODULATED BY 

DNA REPAIR SYSTEMS 

N. Somaiah 1 , K. Rothkamm 2 , F. Daley 3 , A. Pearson 4 , J. R. Yarnold 5 

1 

RADIATION ONCOLOGY & BIOLOGY INSTITUTE; GRAY CANCER INSTITUTE, 

Radiobiology Radiotherapy, Oxford, United Kingdom 

2 

HEALTH PROTECTION AGENCY, Radiation Protection Services, Chilton, 

Didcot, Oxfordshire, United Kingdom 

3 

GRAY CANCER INSTITUTE, Department of Histopathology, Northwood, 

Middllesex, United Kingdom 

4 

INSTITUTE OF CANCER RESEARCH, Academic Radiotherapy, Sutton, 


5 

INSTITUTE OF CANCER RESEARCH & THE ROYAL MARSDEN HOSPITAL, 

Academic Radiotherapy, Sutton, United Kingdom 

Purpose: Sensitivity to fraction size is associated with the proliferative status 

of stem cells in the basal skin epidermis, which are more sensitive to fraction 

size (α/β~4Gy) during the first 3 weeks of radiotherapy (RT) than during 

weeks 4 5 (α/β>10Gy) [1,2]. Molecular processes relevant to cellular recovery 

in vitro and to fraction size sensitivity in vivo include recognition and 

processing of DNA double strand breaks (DSBs). A longer repair half-time 

for homologous recombination repair (HR) compared to non homologous end 

joining has been proposed as a basis for the reduced RT fractionation sensitivity 

of rapidly proliferating tissues [3]. Also, rapidly cycling cells have less 

time than slowly proliferating ones to complete the repair of complex DSB 

prior to DNA replication & mitosis, regardless of fraction size. This study exploits 

accelerated repopulation in human epidermis to investigate changes in 

DSB repair capacity & pathways associated with loss of fraction size sensitivity 

that may be relevant to fractionation sensitivity in other normal tissues &, 

perhaps, tumours. 

Materials: Thirty patients prescribed radiotherapy to a dose of 50 Gy in 25 

fractions of 2.0 Gy over 5 wks to the breast after tumour excision of early 

breast cancer were recruited into the study. The estimated dose per fraction 

to the epidermis was 1.6 Gy. Four mm punch biopsies of breast skin were 

collected at the following time-points:a) 2hrs after 1st fraction from irradiated 

& contra lateral breast.b) 2hrs after 5th fraction from irradiated breast.c) 1hr 

before & 2hr after final fraction from irradiated breast (day 33) 

Results: Formalin fixed paraffin embedded sections of epidermis were costained 

by immunohistochemistry & immunofluorescence for β-1 Integrin 

(epidermal stem cell marker), Ki67 (cell proliferation marker), RAD51 (marker 

for HR) & 53BP1 (DSB marker). The population of β-1 Integrin+ Ki67+ cells 

shows a drop from baseline by day 5 of RT followed by a significant increase 

by day 33 (p=0.001). All epidermal cells show 53BP1 foci following RT, but 

RAD51 foci are present only in a subset of Ki67-expressing cells. Between 

day 1 & 33, preliminary results from 9 patients show an average 3.9 fold 

increase (range 2.0 to 7.2, p=0.001) in the fraction of Ki67-positive cells carrying 

RAD51 foci in the basal epidermis. 

Conclusions: Accelerated repopulation in the epidermis at the end of a 5week 

course of fractionated RT appears to be associated with an increased 

adoption of HR for repairing DSBs. This observation may be relevant to the 

loss of fractionation sensitivity reported in epidermis over the same period 

in clinical studies.References:1. Turesson I & Thames HD. Radiother Oncol, 

1989. 15(2):169-88.2. Hopewell JW, Nyman J & Turesson I. Int J Radiat Biol, 

2003. 79(7): 513-24.3. Lambin P. ESTRO News, 2004. 58: p. 13. 

Adapting Optimized Therapy 

72 oral 

ONLINE CORRECTION OF TRANSLATIONS AND ROTATIONS 

FOR IMRT OF PROSTATE CANCER: PROSTATE, RECTUM, AND 

BLADDER DOSE EFFECTS 

E. Rijkhorst 1 , A. Lakeman 1 , M. van Herk 1 , J. Lebesque 1 , J. J. Sonke 1 

1 THE NETHERLANDS CANCER INSTITUTE - ANTONI VAN LEEUWENHOEK 

HOSPITAL, Department of Radiation Oncology, Amsterdam, Netherlands 

Purpose: To validate a method for online translational and rotational organ 

motion correction, and to quantify and evaluate the accumulated prostate, 

rectum, and bladder dose for several online correction strategies for IMRT of 

prostate cancer. 

Materials: Repeat CT scans of 19 prostate cancer patients were used. Per 

patient, two IMRT plans with a regular (7 mm), and a smaller (4 mm) margin, 

were created. To quantify prostate organ motion, repeat CT clinical target 

volumes (CTVs) were rigidly registered onto the planning CTV. Three online 

strategies were simulated: setup correction, CTV translation correction, 

and CTV translation and rotation correction. A couch shift was used to compensate 

for translations, while rotations were corrected for by using gantry 

and collimator angle adjustments (Rijkhorst et al. 2007). The prostate, rectum, 

and bladder dose were accumulated for each patient, plan, and strategy. 

The minimum CTV dose (Dmin), rectal wall equivalent uniform dose (EUD, 

n=0.13), and bladder surface receiving ≥78Gy (S78), were calculated. 

Results: A 7 mm margin was insufficient with only online setup correction, 

while with online CTV translation correction, it was sufficient (i.e. Dmin ≥95% 

Dprescribed for all cases). A 4 mm margin required additional online CTV rotational 

correction. Margin reduction from 7 to 4 mm led to a decrease in 

average accumulated rectum EUD by 2.8±0.8Gy, and average accumulated 

bladder S78 by 2.0±1.4%. For 4 mm margin plans, the average accumulated 

rectum EUD was smaller than the planned EUD by 2.2±1.8Gy, and insensitive 

to whether or not rotational corrections were applied. 

Conclusions: A 4 mm margin required online translation and rotation correction. 

Margin reduction combined with online corrections would decrease 

the rectum and bladder dose for all patients in our group, allowing safe implementation 

of dose escalation.Rijkhorst EJ, van Herk M, Lebesque JV, Sonke 

JJ, Strategy for online correction of rotational organ motion for intensitymodulated 

radiotherapy of prostate cancer. Int J Radiat Oncol Biol Phys 

2007;69:1608-1617. 

73 oral 

A QUANTIFICATION OF THE INFLUENCE OF ORGAN MOTION 

ON CONFORMAL VERSUS INTENSITY-MODULATED PELVIC 

RADIOTHERAPY FOR PROSTATE CANCER BASED ON THE 

GENERALIZED EQUIVALENT UNIFORM DOSE 

L. Bolstad Hysing 1 , T. Skorpen 1 , M. Alber 2 , L. Fjellsboe 1 , S. I. Helle 1 , L. 

P. Muren 1 

1 

HAUKELAND UNIVERSITY HOSPITAL, Dept of oncology and medical 

physics, Bergen, Norway 

2 

UNIVERSITY HOSPITAL FOR RADIATION ONCOLOGY, Section for biomedical 

physics, Tuebingen, Germany 

Purpose: Several planning studies have shown the superiority of intensitymodulated 

radiotherapy (IMRT) over conformal radiotherapy (CRT) for treatment 

of pelvic lymph nodes in prostate cancer patients. The large mobility 

of the relevant organs at risk (ORs) in the pelvis may however jeopardize the 

normal tissue sparing shown on planned dose. The purpose of the present 

study was therefore to compare an IMRT planning approach (based on one 

CT/contour) with CRT under the influence of organ motion. We hypothesized 

that IMRT would be less robust towards OR motion than CRT. By robust we 

mean that the dose metrics of the plan are predictable to within a tolerable 

uncertainty of the metrics of the applied dose. In other words; does better in 

planning stay better in application, or is the planning advantage of IMRT just 

an illusion? 

Materials: We simulated IMRT and CRT for delivery of 50Gy to the prostate, 

seminal vesicles and pelvic lymph nodes in 20 male patients. Each out of 

these patients had 5-8 treatment CT scans in addition to the planning CT. 

Planning was done in Eclipse without correcting for OR motion. Evaluation 

was performed using both volume parameters (for the bowel) and generalized 

Equivalent Uniform Doses (gEUDs) derived from the CRT and IMRT 

dose matrices and the planning and treatment OR outlines. A volume-effect 

parameter of 4, 12 and 8 was used for calculation of gEUD for bowel, rectum 

and bladder, respectively. For the bowel, the gEUD was normalised to a 

Vref of 200cm3. For each patient and each OR, an average of the treatment 

gEUDs (gEUDtreat) was calculated for CRT and IMRT. The paired t-test was 

used to compare IMRT with CRT and gEUDtreat with gEUDplan. 

Results: The mean gEUDtreat was reduced from 43 to 40 Gy, 47 to 46 

Gy and 48 to 45 Gy with IMRT for bowel, rectum and bladder, respectively 

(p0.05) for any OR, but exceeded 6% for the bowel in 6/20 patients. 

Conclusions: IMRT was better than CRT on planned dose. Internal organ 

motion made all metrics (gEUDs and volume parameters) worse, sometimes 

significantly so. Still, IMRT remained better than CRT also under the influence 

of internal organ motion. The gEUD was less sensitive towards bowel motion 

than volume parameters. For the bowel, gEUD should preferably be calculated 

relative to an absolute reference volume. The examined IMRT planning 

approach (of one contour only) is reasonably robust and therefore considered 

clinically acceptable. 

74 oral 

RELATING THE LOCATION OF BIOCHEMICAL RECURRENCES IN 

PROSTATE CANCER WITH GIVEN LOCAL DOSE USING REPEATED 

FUNCTIONAL MR IMAGING. 

C. Berg 1 , M. R. Moman 1 , M. Philippens 1 , J. Lagendijk 1 , U. van der Heide 

1 , M. van Vulpen 1 

1 UNIVERSITY MEDICAL CENTRE UTRECHT, Radiotherapy, Utrecht, 

Netherlands


Purpose: The use of functional imaging techniques in prostate cancer has 

created the possibility to identify the GTV in the prostate and treat this with 

a higher dosage. To evaluate the effectiveness of such a boosting strategy, 

it is necessary to assess in a large patient group the location of a local biochemical 

recurrence with respect to the given dose distribution. In this study 

we present an imaging strategy designed to visualize the correlation between 

the extent of a biochemical recurrence and the dose distribution. 

Materials: From 2006 325 patients with stage T3 prostate cancer underwent 

prior to radiotherapy an MRI exam to facilitate contouring and identification of 

the GTV. For patients with a biochemical recurrence after the radiotherapy the 

MRI exam was repeated The exam includes 2 anatomical scans: a multislice 

T2 weighted TSE sequence (TR/TE=8400/120 ms) and a balanced SSFP sequence 

(TR/TE=5.3/2.4 ms). For tumour localisation within the prostate we 

use Dynamic Contrast Enhanced (DCE) MRI and Diffusion Weighted Imaging 

(DWI) sequences. The DCE MRI protocol consists of a 3D spoiled gradient 

echo sequence (TR/TE=4.0/2.1 ms, flip angle 16 o ,1x1x5 mm 3 res.) resulting 

in 10 axial slices per dynamic. Scans were repeated 120 times at 2.4s interval. 

8 ml of gadolinium-DTPA contrast was injected. A pharmo-kinetic model 

was fitted to the enhancement data resulting in 3D maps of K trans , kep and 

vep. DWI scans were performed using an EPI sequence (TR/TE=5000/54 

ms) and 3 b-values (300, 500, 1000 s/mm2) from which the apparent Diffusion 

Coefficients (ADC) were estimated. Mutual information registration is 

used to register these images to the MR and CT scans used for treatment 

planning. 

Results: So far, 11 patients with a biochemical recurrence have been 

scanned. The median time to recurrence was 31 months. In 6 cases the 

functional MRI scans suspected a local recurrence which could be verified by 

transrectal ultrasound guided biopsies in 4 patients. For 3 of these 4 patient 

the given dose at the locations of recurrence was 70 Gy for 1 patient 77 Gy. 

Images could be registered. 

Conclusions: Pre and post treatment imaging is necessary to establish the 

relation between the given dose distribution and the location of the recurrence. 

Due to its excellent anatomical and functional contrast, MRI is the 

ideal modality to investigate this relation. Due to the absence of radiation 

burden, MRI can even be applied in follow up imaging to detect the onset of 

a recurrence or establish a baseline reference. 

75 oral 

SENSITIVITY STUDY OF PATIENT RESPIRATORY MOTION UNCER- 

TAINTY ON 4D IMRT PLANNING 

D. Yan 1 

1 WILLIAM BEAUMONT HOSPITAL & RESEARCH INSTITUTE, Radiation 

Oncology, Royal Oak, Michigan, USA 

Purpose: Patient respiratory motion density function (pdf) has been successfully 

included in 4D IMRT planning in managing lung cancer radiotherapy. The 

resulting dose distribution is comparable to those planned using the real-time 

tracking or the gating techniques. However, the motion pdf could vary during 

and between treatment deliveries resulting dose deviation from the one originally 

planned. In this study, we applied clinically observed pdf variation to 

evaluate the effect of the variation on the dose distribution obtained from the 

4D inverse planning. 

S 23 

Materials: 4D inverse planning performed for each of 4 lung cancer patients 

was used. The reference pdf for each voxel was obtained applying 

deformable registration on 4D CT images with target excursion of 1.5~3.0cm. 

Treatment pdf was constructed by deviating the second and higher order moments 

of the reference pdf, meanwhile the baseline (the first order moment or 

the mean) position was assumed to remain 0. This assumption is supported 

by online cone beam CT guided localization and correction. The ranges of the 

higher order moments’ deviation were obtained from clinical measurements 

of 8 lung cancer patients. The treatment dose in organs of interest was then 

accumulated using the treatment pdf and compared with those obtained using 

the reference pdf. The minimal dose (D99%) for target (GTV), and the 

DVH and EUD in lung, heart and cord were used for the evaluation. 

Results: Dosimetric effect of respiratory pattern (pdf) variation is dominated 

by its 2nd order moment (or the standard deviation) variation. The minimal 

dose in GTV decreases 0.9% + 1.1%, -2.8% + 0.6% and 5.5% + 2.1% respectively 

with the reference standard deviation discrepancy of 0.5, 1 and 2 

mm. The pdf variation has minimal effect on lung, heart and cord EUDs. 

Conclusions: Variation in respiratory motion pattern causes dose reduction 

in target. However, the deviation is relatively insensitive to the variation, as 

long as the baseline position of the target remains in the treatment course. 

Previous study has shown a limit variation on the motion pdf standard deviation 

(< 1 mm for 95% lung cancer patients during the conventional radiotherapy 

course). Therefore, 4D IMRT planning with online tumor mean position 

control is a reliable and practical technique in managing patient respiratory 

motion during the lung cancer radiotherapy. 

76 oral 

UNRAVELING INFLUENCES OF PATIENT ERROR SOURCES ON 

BREAST IMRT PLANS BY MEANS OF DEFORMABLE REGISTRA- 

TION 

A. van Mourik 1 , S. R. van Kranen 1 , S. den Hollander 1 , J. J. Sonke 1 , C. 

van Vliet-Vroegindeweij 1 

1 NKI-AVL, Radiotherapy, Amsterdam, Netherlands 

Purpose: Patient setup error and tissue deformation during treatment of 

breast cancer patients lead to variations in position and shape of the target 

volume and alter the originally planned dose distribution. As a result a 

different dose will end up at a different position. The goal of this study was to 

determine the sensitivity of 3 breast RT planning strategies for these patient 

error sources by evaluation of accumulated dose. 

Materials: For 5 patients, 3 original plans were made (Pinnacle 7.6c) with 

identical tangential beam setup: 1. Wedge: forward planning, glancing open 

fields with wedges; 2. SimpleIMRT: inverse planning, ~80% glancing open 

fields, ~20% segments, (clinical standard); 3. FullIMRT: inverse planning, 

100% segments. The impact of setup error and shape changes was unravelled 

by accumulating the dose over 5 fractions, taking the separate and 

combined errors into account. To that end, the dose was recalculated on: " 

original CT after setup translations (T) " deformed CT (see below) (D) " deformed 

CT after setup translations (T&D) The original CT was deformed to 

the CBCT of the day to account for shape changes. Tissue to tissue correspondence 

between planning CT and daily CB scans was established with 

b-spline deformable registration. Resulting deformation fields were used to 

generate a deformed CT for recalculating the dose distributions (according 

to plan 1, 2 and 3) and to deform these distributions back into the original 

planning CT for accumulation. Per plan, target volume coverage (V95) was 

determined for original plan (O), in the presence of translation errors only (T), 

deformation errors only (D) and when both error sources are present (T&D). 

Results: The impact of error sources is reflected in degradation of plan coverage 

(O vs. T, D and T&D, see table). Comparing V95 decrease for translations 

(O-T) and deformations (O-D), translations represent the larger error 

source for plan 1&2. Conversely, for plan 3 deformations seem have a larger 

impact. Underdosage was mainly located near the skin. 

Conclusions: Preliminary results show that impact of error sources on breast 

RT depends on planning technique. Full IMRT plans do not have glancing 

beams and are therefore more susceptible to deformation errors of the breast 

contour. This demonstrates that incorporation of deformation errors provide 

a more realistic estimate of plan deterioration. The difference between D and 

T&D reveals the gain that can be achieved by clinically using an online instead 

of an offline correction protocol.


77 oral 

IN VIVO BEAM PROFILE VERIFICATION OF NARROW HIGH EN- 

ERGY SCANNED PHOTON BEAMS USING PET-CT MEASUREMENT 

OF INDUCED ACTIVITY 

S. Strååt 1 , B. Andreassen 1 , C. Jonsson 2 , R. Holmberg 3 , A. Brahme 1 , P. 

Näfstadius 4 

1 

KAROLINSKA INSTITUTET & STOCKHOLM UNIVERSITY, Medical Radiation 

Physics, Stockholm, Sweden 

2 

KAROLINSKA UNIVERSITY HOSPITAL, Department of Medical 

Physics/Nuclear Medicine, Stockholm, Sweden 

3 

KAROLINSKA INSTITUTET, Medical Radiation Physics, Stockholm, Sweden 

4 

KAROLINSKA UNIVERSITY HOSPITAL, Hospital Physics, Stockholm, 

Sweden 

Purpose: Cancer treatment with narrow high energy scanned photon beams 

provides high accuracy and flexibility in dose delivery which is of major importance 

for advanced treatment techniques such as IMRT where precision is of 

primary importance. It is also suitable for in vivo dose delivery verification 

with PET since positron emitters such as 11 C, 13 N and 15 O are produced by 

(γ,n) reactions in the irradiated tissue when photon energies over 15 MeV are 

used (Janek et al 2006 Phys. Med. Biol. 51 576983). By combining narrow 

high energy photon beam treatment with PET imaging the activated tissue in 

a patient can be measured and it may be possible to detect deviations in the 

delivered dose from that in the treatment plan. This is particularly important 

when IMRT is used and small misalignments can cause severe normal tissue 

side effects and underdosage in the target. 

Materials: The elementary beam used is a 50MV bremsstrahlung beam, 

which is a photon beam generated by 50 MeV electrons incident on a target. 

The accelerator used is the Racetrack Microtron at the Karolinska University 

Hospital. Two thin transmission targets made of 3 and 6 mm Be and 

one thicker full range target consisting of 5 mm W + 7.25 mm Cu are used. 

The elementary photon beam is either stationary or scanned in a desired 

scan pattern on suitable graphite (C) and PMMA (C5H8O2) phantoms. The 

scan pattern is optimized to produce a uniform rectangular field. Scanning is 

performed both with and without collimation. The photoneutron reactions resulting 

in the production of the positron-emitting radionuclides in the graphite 

and PMMA phantoms are 12 C(γ,n) 11 C and 16 O(γ,n) 15 O with 20.4 respectively 

2.04 min half-lives. The induced activity is measured in a PET-CT and 

the positron distribution is compared with the planned dose profile. The distribution 

and density of the produced positron emitters in the irradiated medium 

are also Monte Carlo simulated using Geant4. 

Results: The FWHM of the 50 MV elementary beam, measured 5 mm below 

the surface of a water phantom, at isocenter (SID = 100 cm), is 34, 39 

and 86 mm for 3Be, 6Be and 5W7.25Cu target respectively. The measured 

PET signal will be proportional to the photon fluence convoluted with a point 

spread function, determined by the positron range and physical properties of 

the camera. 

Conclusions: The advantages of using a thin transmission target are twofold. 

Since the photon spectra from thin Be bremsstrahlung targets are harder 

than that from a thick WCu target, this will produce more (γ,n) reactions due 

to better spectral matching of the photoneutron cross section. Furthermore, 

the low energy photon component from a thick target contributes more to 

absorbed dose than a harder high energy photon spectrum, indicating the 

usefulness of narrow photon beam scanning for in vivo dose verification with 

PET. This study shows the need to eventually do real patient dose delivery in 

order to account for biological transport processes in living tissue. 

Applied dosimetry 

78 oral 

4D TUMOUR-TRACKING RADIOTHERAPY: A DOSIMETRIC AND 

GEOMETRIC VERIFICATION USING POLYMER GEL 

S. Ceberg 1 , P. Keall 2 , H. Gustavsson 1 , F. Nordström 1 , J. Zimmerman 3 , 

G. Persson 3 , J. Medin 3 , A. Sawant 2 , M. Svatos 4 , H. Cattell 4 , S. Bäck 1 , 

S. Korreman 3 

1 

LUND UNIVERSITY, MALMÖ UNIVERSITY HOSPITAL, Department of Medical 

Radiation Physics, Malmö, Sweden 

2 

STANFORD UNIVERSITY, Radiation Oncology, Stanford, USA 

3 

THE FINSEN CENTER - RIGSHOSPITALET, Department of Radiation 


4 

VARIAN MEDICAL SYSTEMS, Palo Alto CA, USA 

Purpose: The advantage of 4D tumour-tracking radiation delivery is the ability 

to allow a tighter margin around the target by continuously following its motion. 

However, there are geometric and dosimetric uncertainties associated 

with beam delivery system constraints (such as any possible delay between 

target motion detection and beam repositioning) and output variations (e.g. 

due to dissimilar head-scatter conditions during off-axis irradiation). The aim 

of this study was to perform a geometric and dosimetric verification of a 4D 

dynamic multileaf collimator (DMLC)-based respiratory motion-tracking delivery 

using a 3D polymer gel dosimetry system. 

Materials: A DMLC real-time motion-tracking (RTT) system was used together 

with Varian’s optical real-time positioning system (RPM). A respiratorylike 

target motion, perpendicular to the beam direction and parallel to the 

leaf motion, was simulated mechanically. Three identical 250 ml nPAG 

(3%acrylamide/3%N,N’- methylene-bis-acrylamide) phantoms were irradiated 

with A) a static beam and the gel at rest, B) a static beam and the gel 

in motion, and C) beam tracking and the gel in motion. Magnetic resonance 

imaging was used to evaluate the absorbed dose response. Images were 

acquired using a 1.5T Siemens scanner with a 32 multi-spin echo sequence. 

Comparable measurements were made using a 2D ionisation chamber array 

(PTW). All irradiations were performed using a small circular, r =15 mm, 6 MV 

photon beam. 

Results: As expected, the motion introduced a significant dose-blurring when 

no tracking was applied (fig. A&B). When tracking was applied, this effect was 

compensated for (fig. A&C). The distance between the 50% absorbed dose 

contour of the static and tracked gel-measurements was less than 1 mm for 

96% of the points along the contour (max 1.4 mm). The absorbed dose in 

planes through the depth of dose maximum in the static and tracked gels 

were also compared. A 91% pass ratio was reached for a gamma criteria 

of [3%,3mm] for a region where the absorbed dose was greater than 80%. 

For doses >20% the pass ratio was 82% (fig. D). Apart from a well confined 

region within the treated area, most of the dose points failing the gamma criteria 

occurred in the penumbra region, possibly due to motion induced dosesmearing 

effects. Overall, the 2D array measurements agreed well with the 

gel measurements. However, due to the limited spatial resolution of the 2D 

array a detailed comparison was not possible. 

Conclusions: Geometric and dosimetric measurements of a 4D DMLCbased 

respiratory motion-tracking dose delivery verified the ability to account 

for target motion during radiotherapy. Good agreement in absorbed dose was 

found between the static and tracked measurements. Our findings show that 

high resolution 3D polymer gel dosimetry has a potential to discover possible 

problems with DMLC patterns or beam delivery, and this will be further 

investigated.


79 oral 

PRE-TREATMENT DOSIMETRIC VERIFICATION OF RAPIDARC 

TREATMENTS WITH AN ASI EPID AND THE GLAAS ALGORITHM. 

G. Nicolini 1 , A. Fogliata 1 , E. Vanetti 1 , A. Clivio 1 , S. Korreman 2 , L. Cozzi 

1 

1 IOSI, Medical Physics, Bellinzona, Switzerland 

2 THE FINSEN CENTER - RIGSHOSPITALET, Medical Physics, Copenhagen, 

Denmark 

Purpose: RapidArc (RA) is a Volumetric Modulated Arc Therapy based on 

a single arc where MLC, dose rate and gantry speed are optimised and varied 

simultaneously. Pre-treatment verification of this new delivery was investigated 

with the consolidated GLAaS method using the Varian amorphous 

silicon PortalVision aS1000 (PV-aS1000) system. GLAaS is a calibration 

algorithm based on the separation of measured signal in components from 

primary or transmitted radiation for different field sizes. 

Materials: PV-aS1000 response to variable dose rate was preliminary assessed 

as well as residual support arm motion during rotation. Tests were 

performed on 6 and 18 MV photon beams. PV-aS1000 was positioned at 

SDD=100cm without additional buildup. Delivery was realised in the same 

conditions as for patients. Measurements, converted into dose with GLAaS, 

were compared with dose matrices computed by the Eclipse TPS at dmax 

with the AAA algorithm and a dose calculation grid of 1 mm. To assess RA 

calculation vs. delivery at various stages of the arc rotation, a study was performed 

testing the entire 360 ◦ arc and partial arcs (180 ◦ , 90 ◦ , 45 ◦ , 30 ◦ , 

15 ◦ and 10 ◦ ). Analysis was based on the gamma evaluation (DTA=3mm, 

DeltaD=3%). The Gamma Agreement Index, GAI, percentage of the field 

area with gamma


Purpose: New generation of radiation therapy accelerators requires highly 

accurate dose measurements with high spatial resolution patterns. IMRT 

is especially demanding since the positioning accuracy of all the multi-leafs 

should be verified for each applied field and at any incidence. In the following 

paper, we present a new 2D tissue equivalent dosimeter with high spatial 

resolution that can fulfill these tasks. 

Materials: A plastic scintillator sheet is sandwiched between two polystyrene 

cubes and the emitted light is observed by a high resolution camera (cf. figure 

1). A patented procedure allows efficient discrimination of the scintillation 

proportional to the dose from the parasitic Cerenkov radiation. This extraction 

made on cumulated images taken during an irradiation field at a rate of 

10 images/ second provides high resolution mapping of the dose rate and cumulated 

dose in quasi real time. The dosimeter is tissue equivalent (ICRU-44) 

and works both for electrons and photons without complex parameter adjustment 

since phantom and detector materials are identical. The calibration is 

simple and independent of the irradiation conditions (energy, fluence, quality&). 

Fig. 1. The device is composed of a plastic scintillator placed within 

a polystyrene phantom. To absorb the renkov radiation produced behind the 

scintillator, its back face is black-painted. A gelatin filter prevents the renkov 

light to produce additional scintillation, and a modulation mask allows the discrimination 

of the scintillation. The camera is kept out of the irradiation beam 

by using a mirror included in the bottom polystyrene cube. 

Results: In the proposed paper, we discuss the principle of the dosimeter 

and its calibration procedure. We compare the results btained in photons 

and electrons beams to standard ionization chamber measurements in 

polystyrene. The different measurement pecifications are precisely evaluated 

and compared to other techniques. Finally we present some IMRT field measurement 

and compare the results to TPS and dosimetric films. One example 

of comparison with a standard ioniration chamber is reported in igure 2 in the 

case of 15MV photons and in figure 3 in the case of 9MV electrons. In both 

cases, the agreement is excellent. Fig. 2. Depth dose profiles measured by 

DOSIMAP (left and right) and ionization chamber (right) for 15MV photons: 

the profile is taken at the center of the field, the difference is less than 2% for 

all the positions. 

Conclusions: In conclusion we will present a new 2D dosimeter that exhibit 

two main advantages compared to the existing systems: It is trictly tissue 

equivalent and so does not require complex calibrations. All types of irradiations 

with photons and electrons can be measured without additional calibrations. 

Its second unique capacity is its high spatial resolution of 2mm and the 

capacity to measure the entire dose applied at any position in one cross section. 

These characteristics make it the best choice for rapid and easy control 

of complex irradiation fields. 

82 oral 

HOW WELL CAN UK CENTRES DELIVER HEAD AND NECK IMRT? 

A DOSIMETRY AUDIT FOR THE PARSPORT TRIAL 

C. Clark 1 , H. Chantler 2 , C. Edwards 3 , V. N. Hansen 1 , H. James 4 , G. 

Webster 5 , E. Miles 6 , T. Guerrero Urbano 6 , S. Bhide 6 , M. Bidmead 1 , C. 

Nutting 6 

1 

ROYAL MARSDEN HOSPITAL (SUTTON), Physics, Sutton, United Kingdom 

2 

ADDENBROOKES HOSPITAL, Physics, Cambridge, United Kingdom 

3 

UNIVERSITY HOSPITAL NORTH STAFFORDSHIRE, Physics, Stoke-on-Trent, 


4 

IPSWICH HOSPITAL, Physics, Ipswich, United Kingdom 

5 

CHRISTIE HOSPITAL NHS TRUST, Physics, Manchester, United Kingdom 

6 

ROYAL MARSDEN HOSPITAL, Radiotherapy, London, United Kingdom 

Purpose: PARSPORT was the first multi-centre randomised controlled trial 

of IMRT versus conventional radiotherapy (CRT) for patients with head and 

neck cancer in the UK. Contributing centres underwent a rigorous quality 

assurance program before joining the trial and completed exercises in volume 

delineation, planning, process documentation, a questionnaire and data 

transfer verification(1). Once the centre had started entering patients into the 

trial they received a dosimetry audit visit. 

Materials: The dosimetry audit consisted of treatment planning system (TPS) 

tests, individual field verification films at gantry 0 and combined field film tests 

(gantry angles from the clinical plan). Dose point measurements were also 

made. The TPS audit consisted of geometric volumes testing MLC positioning, 

transmission and relative dose levels (see fig 1). The film and dose 

point tests consisted of a universal patient planned at all centres which was 

transferred onto solid water blocks (for the film tests) or a cylindrical solid water 

phantom for point dose measurements (CIRS 002HN phantom). A PTW 

semiflex ion chamber was used in the CIRS phantom to measure points in 

the primary PTV (PTV1), elective PTV (PTV2) and the spinal cord (SC). The 

measured dose was compared with the dose calculated in the phantom by 

the TPS. The films were analysed using the γ index method of Low et al (2). 

A threshold was applied at 10% and a film was considered to pass if >95% of 

each film gave γ indices of


83 oral 

IPEM GUIDANCE NOTES ON SMALL FIELD MV PHOTON DOSIME- 

TRY 

M. M. Aspradakis 1 , J. Byrne 2 , J. Conway 3 , S. Duane 4 , H. Palmans 4 , K. 

Rosser 5 , J. Warrington 5 

1 

TOMOTHERAPY EUROPE GMBH, Department of Medical Physics - 

Research, Diegem, Belgium 

2 

NEWCASTLE GENERAL HOSPITAL, Department of Regional Medical 

Physics, Newcastle-upon-Tyne, United Kingdom 

3 

WESTON PARK HOSPITAL, Department of Medical Physics, Sheffield, 


4 

NATIONAL PHYSICAL LABORATORY, Ionizing Radiation, Teddington, United 

Kingdom 

5 

ROYAL MARSDEN HOSPITAL, Joint Department of Physics, London, United 

Kingdom 

Purpose: The purpose of this report is to give recommendations on how to 

accurately measure dosimetric parameters in small MV photon beams. 

Materials: Treatment using small photon fields has been an established practice 

in stereotactic radiotherapy for many years. Technological improvements 

in conventional linear accelerators have lead to better mechanical accuracy, 

stability and dosimetric control. At the same time there has been an increasing 

availability in the clinic of standard-, mini- and micro- multi-leaf collimators 

(MLCs) on conventional linear accelerators as well as the introduction of 

new treatment units specifically designed for stereotaxy (Gamma Knife, CyberKnife) 

or intensity modulated treatments (IMRT) (TomoTherapy). These 

technical improvements implicitly encourage the use of treatment field sizes 

which previously would have been the preserve of the stereotactic community.There 

are a number of interdependent problems in the use of small fields. 

First the normal field size definition (FWHM) breaks down. The accurate 

measurement of standard dosimetric quantities in narrow collimated fields 

strongly depends on the size of the detector with respect to the field dimensions 

and the changes in detector response at small beams as opposed to 

larger fields. Some of the standard dosimetric quantities are difficult to measure 

and planning systems’ definitions of data may differ from the local clinic’s 

definition. Some of these problems could cause local differences between 

measurement, prediction and actual dose of the order of 10%.In intensity 

modulated radiotherapy (IMRT), individual small segments may not contribute 

a significant dose in themselves but an IMRT treatment field may comprise of 

many small segments. Dosimetric errors in small segments could therefore 

cause a significant dosimetric error in the whole IMRT treatment. However, 

because IMRT fields are likely to extend over a much larger area, quality control 

testing can benefit from averaging and problems with small segments may 

not be apparent or significant. This is not the case in small individual fields. 

Small fields used to treat small patient volumes may contribute a significant 

proportion of the prescribed dose to the patient. Any dosimetric errors in 

these small fields could therefore cause a significant error in overall delivery 

of prescribed dose. 

Results: The report:" Summarises the problems with small photon beams, 

their dosimetry and modelling by treatment planning systems." Reviews suitable 

detector systems and methods for the determination of small field dosimetric 

parameters." Summarises quality assurance issues in treatment planning 

and delivery involving small fields." Provides clear guidance of good 

practice for the measurement of dosimetric parameters in narrow collimated 

MV beams. 

Conclusions: Currently there is no guidance provided to clinical radiotherapy 

physicists on accurate small field MV dosimetry. This report is unique and its 

aimed readership will be clinical radiotherapy physicists and dosimetrists. 

Treatment of cancer in H&N region and CNS 

84 oral 

INTER AND INTRA OBSERVER VARIATION IN THE GROSS TU- 

MOUR VOLUME (GTV) DELINEATION FOR GLIOBLASTOMA (GBM) 

K. Burton 1 , S. Jefferies 1 , R. Jena 1 , V. Estall 1 , N. Burnet 2 

1 ADDENBROOKE’S HOSPITAL, Oncology, Cambridge, United Kingdom 

2 UNIVERSITY OF CAMBRIDGE, Oncology, Cambridge, United Kingdom 

S 27 

Purpose: Clinical delineation of tumour volume may differ between different 

observers and introduce a geometric uncertainty in the planning process. The 

aim of this study was to assess and quantify the variation that occurs between 

different observers when delineating the GTV for glioblastoma (GBM). The 

work also investigated intra-observer variation when observers delineated the 

same tumour on a number of occasions. 

Materials: Four experienced Neuro-Oncologists were asked to delineate 

the GTV on image data sets of 14 patients previously irradiated for GBM. 

The image data sets consisted of a co-registered planning CT and contrastenhanced 

MRI. The majority of the patients had undergone debulking surgery 

(11); the other 3 had only a biopsy. Each observer was asked to delineate 

the GTV on three occasions, separated by at least a month. A total of 141 

outlines were obtained. 

Results: Comparison was made between the volumes of tissue encompassed 

by the delineated outlines. In five cases (36%) the comparison was 

very good, with the largest and smallest delineated volume being within 20% 

of the mean. This included all the biopsy only cases. However, in 5 cases a 

variance greater than 40% was seen. Review of these cases revealed that in 

all 5 the difference was as a result of post-operative meningeal enhancement 

that had been included in the GTV by some observers but not others. Additionally, 

a calculation was made of the 3D position of the isocentre of each 

delineated GTV using the treatment planning system, and the differences 

compared. The mean difference for each observer, calculated from their three 

outlines, was compared to the means for the other observers. A difference 

in the isocentre position greater than 0.4cm was observed in three cases, 

and once again these were post-operative cases where the meningeal enhancement 

had been included by some and not others. However, differences 

were less than 0.3cm in 80% of comparisons. Intra-observer variation was 

assessed using similar methods and revealed great consistency. Observers 

that chose to include meningeal enhancement were consistent in their approach 

and vice versa. 

Conclusions: The study revealed that in the majority of cases the variation 

between different experienced Neuro-Oncologists when delineating the 

GTV for GBM was small. However, where patients had undergone debulking 

surgery prior to radiotherapy the decision to include meningeal enhancement 

in the GTV differed between observers. Support from radiologists during the 

planning process or use of advanced imaging modalities may improve this 

area of uncertainty. 

85 oral 

THE INFLUENCE OF INTEROBSERVER VARIATION ON ORGANS 

AT RISK IN HEAD AND NECK CANCER. 

E. Lamers 1 , C. Rasch 1 , C. van Vliet 1 

1 NETHERLANDS CANCER INSTITUTE-ANTONI VAN LEEUWENHOEKHUIS, 

Radiotherapy, Amsterdam, Netherlands 

Purpose: Delineations are of crucial importance for inverse treatment planning. 

Recently, work has focussed on decreasing the interobserver variation 

for the GTV and CTV. However, also for the OARs the interobserver variation 

needs to be as small as possible. This is important to make sure that the resulting 

treatment plan is safe for the OARs, regardless of the observer. In this 

study the variation in delineated volumes of the OARs for a head and neck 

patient were quantified, together with its effect on the dose to the OARs. 

Materials: Axial CT-slices of a nasopharynx T4N1M0 case were used for 

delineating several OARs. Accurate work instructions and delineation atlases 

were available and emphasised during the study. Nine observers delineated 

the applicable OARs. For one delineation set, a treatment plan was made 

to quantify the effect of the interobserver variation on the dose delivered to 

the OARs. The total dose prescribed for this case was 70 Gy simultaneously 

given in 35 fractions of 2.0 Gy, with 35 x 1.65 Gy for the elective nodes. 

Treatment planning was performed in Pinnacle version 8.0h. 

Results: For all OARs, we tabulated the average of the delineated volume 

and its SD, as well as the lowest and the highest maximum dose for the nine 

observers (table 1). Significant variations were present for almost all OARs. 

These OARs show remarkable differences in the delineated volume and a 

wide variety in the physical dose. This is not only due to the difference in 

the size of the delineated volume between the different observers, but also to 

differences in their position. 

Conclusions: Due to advances in the treatment techniques (such as adaptive 

techniques and dose escalation), the treatment techniques are more tailored 

to tolerances of the OARs. As a result, the impact of OAR delineation 

variation is comparable to the GTV/CTV delineation variations. These effects 

increasingly need to be taken into account.


86 oral 

NORMAL STRUCTURE SPARING WITH PARTIAL LARYNGEAL RA- 

DIATION FOR T1A GLOTTIC CANCER: DOSIMETRIC EVALUATION 

OF VARYING PTV MARGINS AND RADIATION TECHNIQUES. 

J. Roussos 1 , J. Waldron 2 , A. Bayley 2 , L. Dawson 2 , B. Cummings 2 , J. 

Kim 2 , J. Rigash 2 , S. Breen 3 , B. O’Sullivan 2 

1 PRINCESS MARGARET HOSPITAL, Radiation Therapy, Toronto, Canada 

2 PRINCESS MARGARET HOSPITAL, Radiation Oncology, Toronto, Canada 

3 PRINCESS MARGARET HOSPITAL, Radiation Physics, Toronto, Canada 

Purpose: T1a glottic cancer is highly curable with local radiotherapy delivered 

with a parallel-opposed pair of beams. This technique results in irradiation of 

a volume of neck significantly greater than the target. Treatment modification 

may improve long-term function and ameliorate risk of late effects. This work 

describes the variation in dose to normal structures for four different radiation 

treatment plans and varying PTV margins for T1a glottic cancer. 

Materials: Two target volumes were defined for five cases of T1a glottic cancer: 

the original GTV and a partial glottic CTV, which included the GTV and 

entire ipsilateral cord with a tissue margin of 5 mm. Two PTVs were generated 

as 5 and 3 mm expansions of the CTVs . Organs at risk (OAR) included 

ipsilateral and contralateral common carotid arteries (IC, CC), ipsilateral and 

contralateral arytenoid cartilages (IA, CA), contralateral vocal cord (CVC), 

post cricoid pharynx (PCP) and spinal cord. Four treatment plans were produced: 

lateral parallel opposed pair (POP); anterior wedge pair (AWP); opposed 

obliques (OOB); and five-field IMRT. Dose distributions were normalized 

so that 95% of the PTVs received 100% of the dose. Mean doses to the 

OR were compared for all treatment techniques and PTV margins of 5 and 

3mm. 

Results: The average (and range) of the mean dose for each OAR are expressed 

as a percentage of prescribed dose for each plan with 5mm and 

3mm PTVs respectively in the table below. Spinal cord dose was

MONDAY, SEPTEMBER 15, 2008 POSTER DISCUSSION 

image-guided supine CSI technique was developed at UCH. 

Materials: The new technique was piloted with paediatric patients with a 

view to reducing the numbers of children requiring GA. All patients were immobilised 

using a 5 point Sinmed Posicast shell with their necks extended in 

order to avoid the spinal fields exiting through the mandible. Further immobilisation 

was provided by custom-made hip immobilisers. A planning CT was 

performed on a GE Lightspeed 16 slice scanner and patients planned with a 

moving gap technique with MLCs to shield critical organs. The junction between 

the cranial and spinal fields was dosimetrically matched and all gaps 

were treated daily. Segments and low weighted boost fields were used to 

compensate for the variation in depth of the spine. All patients were treated 

with 6MV on a Varian 2100 CD linear accelerator with OBI. An anterior setup 

field with a skin-rendered image at the spine longitudinal Isocentre position 

was used for daily verification of an accurate inferior shift to the spine Isocentre 

from the cranial Isocentre. This was complemented with weekly cranial 

and daily online spinal position verification with orthogonal kV imaging. 

Results: As of March 2008, 7 patients have been treated with this technique 

(with only one under GA due to their young age.) Of the remainder, 4 would 

have been under GA if treated prone and 2 patients were able to be entered 

into the HART trial. Data gathered from the imaging will allow a review of 

set-up tolerances with regards to cranial Isocentre, cribiform plate coverage, 

spine straightness and curvature. Radiographers, play therapists and anaesthetists 

find the technique easier for the patient. 

Conclusions: The supine positioning reduces the number of children requiring 

GA and if required, enables safe administration of anaesthesia and 

monitoring during treatment. This technique provides improved stability and 

reproducibility in patient setup with no patients to date requiring re-planning. 

In addition, pre-treatment online verification of patient setup and position improves 

treatment accuracy and may lead to a reduction of planning margins. 

Poster discussion 

Poster Discussion - physics 

89 oral 

S 29 

CONFIDENCE INTERVALS ON NTCP ESTIMATES FOR INDIVIDU- 

ALISED DOSE-PRESCRIPTION 

E. Rutkowska 1 , C. Baker 1 , C. Eswar 2 , J. Fenwick 2 , J. Littler 2 , Z. Malik 2 , 

A. E. Nahum 2 

1 UNIVERSITY OF LIVERPOOL, Medical Imaging Radiotherapy, School of 

Health Sciences, Liverpool, United Kingdom 

2 CLATTERBRIDGE CENTRE FOR ONCOLOGY (CCO), Department of Physics 

and Radiotherapy, Wirral, United Kingdom 

Purpose: The clinical use of NTCP predictions is limited by the uncertainties 

in the model parameters, which are derived from a population of patients. 

Associated confidence intervals (CI) would give the clinician valuable information 

about the uncertainty in the NTCP prediction, for a given dose plan and 

prescription dose (Dpr). The aim of this work is to show how such confidence 

intervals can be derived from the literature or local clinical data, and used 

together with estimates of TCP to facilitate individualised dose-prescription. 

Materials: We have used the LKB and the relative seriality models to estimate 

NTCP (α/β=3 Gy), and the Marsden model for TCP (α=0.31 Gy -1 , 

α/β=10 Gy, σα=0.062 Gy -1 , ρcl=107 cm -3 , clonogen dblg time 3 days, 21 

days to prolfn. start). A probability distribution (PD) method (Gagliardi, PhD 

thesis, Stockholm Uni. 1998; Schilstra & Meertens, IJROBP 2001) was used 

to calculate NTCP with CI for different DVHs. NTCP parameters were fitted 

to clinical data for radiation pneumonitis vs. mean lung dose (MLD) collected 

from the literature. Calculations were performed on data from 31 patients 

treated for lung cancer at CCO. For each of these 31 patients, NTCP with CI 

was calculated from the DVH of total lung GTV (TL-GTV), as well as TCP 

and complication-free control (CFC) from the GTV DVH, for a range of possible 

Dpr. 

Results: Our parameter estimates were very similar to published parameter 

estimates from clinical studies. This indicates that the PD method based on 

MLD data from the literature is consistent with other fitting methods. Ideally, 

if enough local clinical data is available, the NTCP with CI can be calculated 

with a three-parameter PD, based on DVHs instead of MLD as input data. 

As more local outcome data is accumulated, the CI on NTCP estimates will 

decrease and be tailored to local treatment techniques. 

Conclusions: Together with an estimate of TCP, the NTCP for a range of 

Dpr can be a guide for the clinician in finding the optimal dose, as a tradeoff 

between local control and complication probabilities. The CI of the NTCP 

estimates give an indication of the uncertainty in the predicted response of 

an average patient, for a given dose plan and Dpr. Currently at CCO, for 

the standard 55 Gy to the tumour, the patient in the figure would achieve (on 

the average) NTCP=8.5% and TCP=42%. However, with individualised doseprescription 

she/he might receive 63 Gy (NTCP=10% at the lower end of the 

CI), resulting in a significantly increased TCP (71%), or 51 Gy if the dose 

were chosen based on the upper limit of the CI for the NTCP (TCP=25%). 

The clinical choice of Dpr may also be influenced by the health status of the 

individual patient, taking into account co-morbidities.

S 30 POSTER DISCUSSION MONDAY, SEPTEMBER 15, 2008 

90 oral 

AN ANALYTICAL APPROACH TO SINGLE ARC INTENSITY MOD- 

ULATED ARC THERAPY (IMAT) WITH DYNAMIC MULTILEAF 

COLLIMATORS 

R. Loeschel 1 , W. Hoegele 1 , B. Dobler 2 , R. Cormack 3 , L. Chin 3 , P. 

Zygmanski 3 

1 

UNIVERSITY OF APPLIED SCIENCES, Department of Computer Science 

and Mathematics, Regensburg, Germany 

2 

UNIVERSITY OF REGENSBURG, Department of Radiotherapy , Regensburg, 

Germany 

3 

BRIGHAM AND WOMENS HOSPITAL AND HARVARD MEDICAL SCHOOL, 

Department of Radiation Oncology, Boston, USA 

Purpose: The purpose of this study is to introduce a method to deliver a 

conformal dose distribution for concave targets by intensity modulated arc 

therapy (IMAT) with a dynamic multileaf collimator (dMLC) using one single 

gantry rotation only. 

Materials: The modulation of the beam profile is achieved by a periodically 

piecewise linear motion of the dMLC. Under the assumptions of such a specific 

dMLC motion pattern, the inverse problem to find the beam profile and 

the leaf movements is reduced to a linear problem. This can be solved using 

the Projection Theorem, which yields a small system of linear equations and 

the solution is guaranteed to be unique. Simplified scatter and attenuation 

are included in the model. We analyzed the dependence on the dose rate 

of the accelerator, the properties of the dMLC, and the geometry of the target. 

The studies were performed on various 3-dimensional radial symmetric 

targets (PTV) encompassing an organ at risk (OAR) in a cylindrical patient. 

Target radii were varying in cranio-caudal direction between 4 cm and 10 cm 

and OAR radii between 2 cm and 8 cm. 

Results: A motion pattern for continuous dMLC movement during continuous 

gantry motion is derived, which allows achieving a highly conformal and 

homogeneous dose distribution in the PTV, with a minimum dose of 95% and 

a maximum dose of 105% of the prescription dose for all patient geometries 

studied. The dose to the OAR could be reduced to 50% of the prescription 

dose within 6 mm from the boundary to the PTV. Plan quality and treatment 

time are dependent on the velocity of the leaf motion. The above mentioned 

plan quality with a fraction dose of 1.8 Gy delivered at a dose rate of 100 

cGy/min can be achieved in a total treatment time of about 10 min at a maximum 

velocity of the dMLC of 3 cm/s. Higher fraction doses could be delivered 

in the same time using a higher dose rate. Reduction of treatment time for 

unchanged plan quality is limited by the speed of the dMLC in the actual generation 

of accelerators. It is therefore at the moment only possible at the cost 

of changed plan quality. 

Conclusions: A new method has been developed to achieve highly conformal 

and homogeneous dose distributions for concave targets encompassing 

OAR with one single gantry rotation only. The dMLC motion is intuitive and 

can be derived by analytical methods. The method has been proven for radial 

symmetric targets. The extension to other geometries will follow the same 

intuitive pattern. 

91 oral 

HIGH PRECISION OBJECTIVES FOR IMRT OPTIMIZATION USING 

PINNACLE 

R. Bohoslavsky 1 , M. Witte 1 , M. van Herk 1 


Purpose: Although triangulated surface meshes are available in the Pinnacle 

treatment planning system, the objective functions for IMRT optimization rely 

on volumes described as contours on the CT slices. A set of replacement 

objectives was developed to exploit the increased definition of mesh-based 

volumes, enabling high precision IMRT optimization. 

Materials: A customized set of objectives was created for the research version 

of the Pinnacle treatment planning system. These functions reach a high 

spatial accuracy by interpolation over the dose grid (usually 4 mm), and by 

performing Monte Carlo volume integration of triangulated regions of interest 

(ROIs). This results in a higher accuracy of the cost value evaluation. Small 

structures with dimensions of the order of the dose grid resolution, such as 

optical nerves (see Fig), may benefit the most from this refinement. We compared 

the objective functions provided by Pinnacle with our high precision 

objectives, using the treatment plan of a head and neck cancer patient. We 

first optimized applying the original Pinnacle functions until a minimum of the 

total cost was achieved. Next, we applied our new functions and continued 

optimization. DVHs based on the triangulated ROIs (i.e., with a high precision) 

were computed for both resulting dose distributions. 

Results: The higher order accuracy of the cost evaluation did require more 

computation time during initialization (a few minutes), but the final optimization 

processs was not noticeably slowed down. The improved cost evaluation 

results in different cost function values, and slightly different dose distributions. 

PTV coverage was improved somewhat without violating organs at risk 

(OARs) dose constraints, basically because the OARs are described with a 

higher resolution. Further analyses will determine whether small organs at 

risk can be more effectively spared without compromising target coverage. 

Conclusions: High precision IMRT optimization based on surface meshes 

can be performed with limited increase of computational time. Resulting treatment 

plans are very similar to the reference plan using standard optimization 

techniques. In general, the differences are small unless a very high spatial 

accuracy is required, such as for small structures like the optic nerve. 

92 oral 

ASSESSMENT OF TARGET VOLUMES AND DOSE COVERAGE 

IN 4D IMAGING AND PLANNING OF LUNG CANCER PATIENTS 

TREATED WITH STEREOTACTIC BODY RADIOTHERAPY (SBRT) 

I. Chetty 1 , I. Ouyang 1 , N. Wen 1 , D. Liu 1 , Q. Chen 1 , D. Babij 1 , I. Aref 1 , 

B. Movsas 1 , M. Ajlouni 1 

1 HENRY FORD HEALTH SYSTEM, Radiation Oncology, Detroit, USA 

Purpose: To compare target volumes assessed via 4D and free-breathing CT 

for patients treated with peripheral lung lesions and to determine the impact 

of 4D treatment volumes on IMRT treatment plans. 

Materials: The target volumes of 5 lung cancer patients imaged using 4D- 

CT and treated with hypo-fractionated SBRT (12 Gy/Fxn x 4Fxn) were retrospectively 

analyzed. For each patient 6-to-8 CT datasets were acquired 

between inhale and exhale respiratory phases on a Philips 16 slice 4D-CT 

scanner. The GTV was segmented on each dataset using a maximum intensity 

projection (MIP) method and an ITV (ITV4D), representing the composite 

of GTVs, was formed. The ITV4D was expanded 5 mm uniformly to generate 

a PTV (PTV4D). The GTV was also contoured on the free-breathing 

scan and expanded using population-based margins of 5 mm and 10 mm in 

the axial and longitudinal planes, respectively, to form a free-breathing-based 

PTV (PTVFB), following RTOG protocol #0236. Additionally, a composite 

of GTVs contoured on only the inhale and exhale scans was generated to 

form the ITVInh_Exh; this volume was expanded 5 mm uniformly to form the 

PTVInh_Exh. IMRT treatment plans were optimized using each of PTV4D, 

PTVFB, and PTVInh_Exh, while minimizing the dose to normal lung tissue. 

All DVHs were converted to biologically effective dose (BED) using the linearquadratic 

model. Dose coverage to relevant target volumes was evaluated 

using generalized equivalent uniform dose (gEUD). NTCP, mean lung dose 

(MLD) and V20 were assessed as dose metrics of healthy lung tissue. 

Results: For 3 patients, PTV4D was substantially larger than PTVFB (average 

increase of 33%; max.=65%). For these cases, plans optimized based 

on the PTVFB showed significant reductions in the gEUD of the PTV4D relative 

to that of the PTVFB; average and max. reductions were 9.4% (8 Gy) 

and 14% (11.6 Gy) for a PTVFB gEUD of 85 Gy. For the remaining two 

patients, volumes were equivalent in one case and PTV4D was 11% smaller 

than PTVFB in the other case; gEUD differences between PTV4D and PTVFB 

were less than 1% in these plans. ITVInh_Exh was smaller than ITV4D in all 

cases (mean=31%; max.= 78%, smaller) suggesting that the inhale and exhale 

breathing phases sometimes fail to capture the largest extents of tumor 

motion in the respiratory cycle. Because tumor volumes in this study were 

small (ave. GTV4D = 21cc; range = 4-35 cc), the volume of irradiated healthy 

lung was limited. Therefore differences in NTCP, MLD and V20 between IMRT 

plans optimized using the various target volumes were inconsequential. 

Conclusions: Results suggest, based on 4D imaging and planning, that the 

use of population-based margin expansions may not adequately account for 

tumor motion of peripheral lung tumors. This may be of increased importance 

in the SBRT setting, where the overall effects of motion may be escalated 

given the small number of fractions. Acknowledgement NIH R01-CA106770


93 oral 

AMBIGUITY IN DEFINITION OF A DOSE PAINTING TARGET 

R. Jeraj 1 , K. McCall 1 , P. Harari 2 , M. Mehta 2 , M. Ritter 2 , S. Bentzen 2 , J. 

Nickles 1 , S. Perlman 3 

1 

UNIVERSITY OF WISCONSIN, MADISON, Medical Physics, Madison WI, 

USA 

2 

UNIVERSITY OF WISCONSIN, MADISON, Human Oncology, Madison WI, 

USA 

3 

UNIVERSITY OF WISCONSIN, MADISON, Radiology, Madison WI, USA 

Purpose: Biological heterogeneity of tumors is responsible for spatially variable 

radiosensitivity. Selective dose escalation in biologically resistant parts 

of the tumors most often termed dose painting - would lead to improved tumor 

treatment control. The biological properties most often considered for dose 

painting are highly metabolic regions, highly proliferative regions or regions 

of increased tumor hypoxia. The obvious question appears about ambiguity 

of the definition of the potential dose painting target. 

Materials: Head and neck, lung and esophagus patients have been 

scanned with three different PET imaging agents 2-fluoro-2-deoxy-D-glucose 

(FDG), as a surrogate of tumor metabolism, 3-deoxy-3-fluorothymidine 

(18F-FLT), as a surrogate of tumor proliferation and Cu-diacetyl-bis(N4methylthiosemicarbazone) 

(61Cu-ATSM) as a surrogate of tumor hypoxia. All 

scans were static acquired at 60 minutes for FDG-PET and FLT-PET and 3 

hours post-injection for CuATSM-PET. The standardized uptake values (SUV) 

distributions were used in the analysis. The CT data between the imaging 

sessions was co-registered and the corresponding PET data compared and 

analyzed. 

Results: Strong biological heterogeneity has been observed for all investigated 

biological phenotypes. The level of heterogeneity has been similar for 

each tumor and all three phenotypes. Spatial correlation between the biological 

heterogeneities revealed two distinctive types one, where all biological 

phenotypes spatially match well each other and one, where different biological 

phenotypes spatially do not show any particular correlation. In the later 

case, overlapping regions might exist, but not necessarily. 

Conclusions: While for some cases, all three investigated biological phenotypes 

metabolism, proliferation and hypoxia could be used to define a 

spatially robust target for dose painting, in most cases the dose painting target 

can not be unambiguously defined. More work is needed to establish 

relevant and optimal dose painting target before dose escalation based on 

biological properties is safely used in clinical setting. 

94 oral 

VOLUMETRIC MODULATED ARC THERAPY (VMAT) VS. SERIAL 

TOMOTHERAPY AND SEGMENTAL (STEP AND SHOOT) IMRT FOR 

BOOST TREATMENT OF PROSTATE CANCER 

D. Wolff 1 , F. Stieler 1 , Y. Abo-Madyan 1 , M. Polednik 1 , S. Mai 1 , V. Steil 1 , 

F. Wenz 1 , F. Lohr 1 

1 UNIVERSITY MEDICAL CENTER MANNHEIM, Department of Radiation 

Oncology, Mannheim, Germany 

Purpose: VMAT is about to be established clinically on a wide basis and may 

increase the efficiency of Intensity Modulated Radiotherapy (IMRT) treatment. 

The goal of this investigation was to compare VMAT to established IMRT 

delivery techniques of serial Tomotherapy and segmental IMRT for prostate 

cancer. 

Materials: Using CT data sets of 9 patients treated for prostate cancer, treatment 

plans for all three techniques were created. Segmental IMRT was 

planned for a conventional MLC (Elekta MLCi, 2x40 leaves, 1cm) and serial 

Tomotherapy for the MIMiC Multivane-Collimator (NOMOS, Corp.), using 

Corvus 6.3 (Nomos; Pencil beam). VMAT was planned with ERGO++ R1.7 

(3D Line Medical Systems/Elekta; Pencil beam). Segmental IMRT plans with 

MLC used 7 isotropic beams. Serial Tomotherapy plans were calculated in 

1cm mode and for a 300 ◦ rotation. VMAT plans were created with a 360 ◦ and 

two 100 ◦ rotations. Evaluation of plan quality used metrics of conformity index 

(CI=Vtissue D99%/Vtarget), homogeneity index (HI=Dmax/Dprescribed), 

dose to normal tissue and the isodose which encompasses 95% of the target 

volume. For conformity index dose to 99% of target was used instead of 

Dmin. 

Results: Median indices for conformity and homogeneity of the Corvus plans 

were: for MIMiC CI 1,5 / HI 1,19; MLC based segmental IMRT CI 1,75 

/ HI 1,15; and VMAT plans CI 1,63 / HI 1,1. 76Gy. The resulting median 

doses to organ at risk (OAR) for (MIMiC/MLC/VMAT) were: for anterior 

rectum (52,2Gy/52,4Gy/53,1Gy), posterior rectum (32,3Gy/33,5Gy/34,6Gy) 

and bladder (44,9Gy/44,1Gy/52,8Gy). Volumes of normal tissue receiving 

≥70% of prescribed dose (53Gy) for (MIMiC/MLC/VMAT) were 

627ml/669ml/622ml, for ≥50% (38Gy) 1158ml/1496ml/1165ml and for 

≥30% (23Gy) 3109ml/3601ml/3272ml. Dose encompassing 95% of PTV 

was (MIMiC/MLC/VMAT) 69,8Gy/65,5Gy/68,4Gy. Median treatment time 

(MIMiC/MLC/VMAT) was 15min/7,5min/3min. 

Conclusions: Rotational therapy techniques showed higher conformity, coverage 

and lower normal tissue exposure. Homogeneity and dose to posterior 

rectum were similar for all three approaches. VMAT plans are deliverable 

S 31 

within a 3minute time slot which is the most efficient treatment option compared 

to the MIMiC- and MLC based approaches. 

95 oral 

BIOLOGICAL TARGET VOLUME FOR LESIONS WITH INHOMOGE- 

NEOUS ACTIVITY DISTRIBUTION IN PET 

R. Bundschuh 1 , G. Delso 1 , M. Essler 1 , A. Martínez-Möller 1 , S. Astner 2 , 

S. Nekolla 1 , S. Ziegler 1 , M. Schwaiger 1 

1 

KLINIKUM RECHTS DER ISAR DER TU MÜNCHEN, Nuclear Medicine, 

München, Germany 

2 

KLINIKUM RECHTS DER ISAR DER TU MÜNCHEN, Radiotherapy, München, 

Germany 

Purpose: Tumor volume segmentation based on biological imaging, e.g. 

PET, is of great interest in radiotherapy treatment planning. Currently most 

algorithms are based on a threshold which seems to be appropriate in phantom 

studies with homogeneously filled spheres. In general, tumors can not 

be considered homogeneous (e.g. central necrosis). Therefore we analyzed 

segmentation methods for inhomogeneous lesions. 

Materials: Three segmentation-algorithms were compared: threshold of 

maximum (M1) or mean (M2) activity uptake in the lesion, and a gradient 

method based on the Marr-Hildreth operator (M3). Data from 4 phantom 

measurements using radioactive wax simulating inhomogeneous lesions (40 

mm diameter) of different activity distribution were used to compare the different 

methods. In addition, Monte Carlo simulations were done to simulate 

inhomogeneous lesions of different size (2050 mm diameter) in the lung of a 

patient. Practicability of the algorithms was additionally tested with 10 data 

sets of patients with lung-lesions. 

Results: In the phantom study lesion volumes determined by M1 (M2; M3) 

were 54 (48; 3)% too small in case of higher activity concentrations in the 

center of the lesion. With lower activity concentration in the center of the lesion, 

M3 showed with 20% error only a slightly improved result compared to 

M1 (26%) and M2 (30%). For homogeneous lesions the results of all three 

methods were within 3% of the real volume. Similar results were found with 

the Monte Carlo data: All methods worked well in the homogeneous case, M1 

and M2 resulted in underestimation of the volume of up to 77% in inhomogeneous 

lesions. For M3 this underestimation was much lower with a mean of 

15.3% for the inner to outer activity concentration of 3:1. All results of the 

simulated data are displayed in the table. 

Conclusions: In case of inhomogeneous uptake, current threshold based 

segmentation methods fail. Gradient based methods are superior in this case. 

96 oral 

FULLY AUTOMATED ON-LINE CORRECTION FOR INTRAFRACTION 

PROSTATE MOTION BY CONTINUOUS IMAGING OF FIDUCIAL 

MARKERS 

H. de Boer 1 , V. Rajan 1 , J. Barnhoorn 1 , T. Mutanga 1 , D. Wentzler 1 , B. 

Heijmen 1 

1 ERASMUS MC - DANIEL DEN HOED, Radiotherapy, Rotterdam, Netherlands 

Purpose: We apply a fast, automated method for prostate targeting on implanted 

fiducial markers. Using crossfire kV and MV beam imaging, this stereographic 

targeting (SGT) method yields systematic errors Σ (SD) < 0.5 mm 

and random errors σ (SD) < 1 mm for the prostate in < 1 min (Mutanga 

IJROBP 2008). These small errors hold directly before fraction delivery. Here 

we propose an extension to also correct for potential intrafraction motion: 

iSGT. 

Materials: We studied intrafraction motion in 10 IMRT and 10 non-IMRT patients. 

Due to several reasons (fraction dose, number of beams, dose rate) 

IMRT treatments took on average longer (10 min) than non-IMRT treatments 

(5 min). kV/MV imaging and correction by SGT was applied (Elekta Synergy), 

using an integrated remote couch control (RCC). The subsequent iSGT procedure 

can be applied for any treatment beam, or only for selected beams. 

The (fully automated) procedure is: (1) image the first few MU (for IMRT, we 

used a segment showing all markers), (2) automatically register markers, (3) 

if displacement > 3 mm, execute correction by RCC, and (4) deliver remaining 

beam dose. As intrafraction motion is mainly in cranial-caudal (CC) and 

anterior-posterior (AP) directions, we studied efficacy if iSGT is applied to 

the 110 ◦ and 250 ◦ beams in our treatments. A lateral validation kVI was


obtained after the last beam. To report the influence of intrafraction motion 

(corrections), effective systematic and random errors (Σeff and σeff) were 

calculated by time-weighed averaging of marker positions in the images. The 

automatic marker registration successrate was determined by comparison 

with manual registration of 690 MV images. 

Results: Directly after SGT correction Σ < 0.6 mm and σ < 0.9 mm for all 

patients. For non-IMRT treatments, Σeff and σeff were only slightly larger, 

but for the longer IMRT treatment times the systematic errors doubled: Σeff = 

1.2 mm. This increase could be traced to reproducible intrafraction changes 

in patient composure. Nevertheless, iSGT could reduce these errors to their 

initial values, yielding Σeff = 0.6 mm and σeff = 0.9 mm (both AP and CC). 

Marker registration took < 2 sec and had a successrate of 97%. 

Conclusions: Intrafraction motion can limit high precision prostate targeting, 

especially for treatment times > 5 min and in specific patients. On-line 

correction by iSGT requires no extra imaging dose (only MV imaging), adds 

negligible treatment time and can reduce intrafraction motion to negligible 

levels. 

97 oral 

COMPARISON OF TWELVE DEFORMABLE REGISTRATION 

STRATEGIES IN ADAPTIVE RADIATION THERAPY FOR THE 

TREATMENT OF HEAD AND NECK TUMORS. 

P. Castadot 1 , J. Lee 1 , A. Parraga 2 , X. Geets 1 , B. Macq 2 , V. Grégoire 1 

1 UNIVERSITÉ CATHOLIQUE DE LOUVAIN, Center for Molecular Imaging and 

Experimental Radiotherapy, Brussels, Belgium 

2 UNIVERSITÉ CATHOLIQUE DE LOUVAIN, Communications and Remote 

Sensing Laboratory, Brussels, Belgium 

Purpose: Modifications of patient’s anatomy occur during head and neck 

(HN) radiotherapy (RT). These modifications may impact on the dose distribution 

to Target Volumes and Organs At Risk. Adaptive radiotherapy (ART) 

whereby patients are re-imaged and re-planned during treatment is a possible 

strategy to improve treatment delivery. It however requires the use of 

deformable registration (DR) algorithms that need to be properly validated on 

clinical material. 

Materials: Twelve voxel-based DR strategies were compared on a dataset 

of 5 patients imaged with computed tomography (CT) before and once during 

RT (on average after a mean dose of 36.8 Gy): Level-set (LS), Levelset 

in multi-resolution (LSMR), Demons’ algorithm in multi-resolution (DMR), 

DMR followed by LS (DMR-LS), Fast free-form deformable registration via 

calculus of variations (F3CV) and F3CV followed by LS (F3CV-LS). The use 

of an edge-preserving denoising filter applied to the registered images and 

combined to all the aforesaid strategies was also tested (fLS, fLSMR, fDMR, 

fDMR-LS, fF3CV, fF3CV-LS). All these strategies were compared to a rigid 

registration based on Mutual Information (MI, fMI). Chronological and antichronological 

registrations were also studied. The various DR strategies were 

evaluated using a volume-based criterion (i.e. Dice similarity index, DSI) and 

a voxel intensity criterion (i.e. correlation coefficient, CC) on a total of 18 

different manually contoured volumes. 

Results: For the DSI analysis, the best 3 strategies were DMR, fDMR-LS, 

and fDMR with median values of 0.86, 0.85 and 0.85, respectively; corresponding 

Inter Quartile Range (IQR) reached 9.6%, 10% and 10.2%. For 

the CC analysis, the 3 best strategies were fDMR-LS, DMR-LS and DMR 

with median values of 0.97, 0.96 and 0.94, respectively; corresponding IQR 

reached 11%, 9% and 15%. Concerning the time sequence analysis, the antichronological 

registration (all deformable strategies pooled) showed a better 

median DSI value (0.84 vs 0.83, p


images were used to calculate the daily dose variation in these organs, using 

an in-house developed Monte Carlo-based dose calculation system. In part 2 

of our study we evaluated the use of contrast imaging based on novel elastic 

microspheres for imaging of the prostate in canine subjects. A phantom for 

contrast imaging was designed. 

Results: The figure shows the effect of a typical prostate shift in a cancer 

patient on a Monte Carlo dose distribution. The shifts of the isodose lines 

in the A/P direction can be clearly seen in the left panel. After correction of 

the patient setup in three directions, the improved dose distribution can be 

seen in the right panel. This procedure was repeated for in total 644 fractions 

for 32 patients. Without setup correction, dose errors in D95 exceeding 10% 

in some cases were noted. Although the target coverage is much improved 

after setup correction, a residual difference compared to the planned dose 

remains. This amounted to no more than a few percent. The canine study 

with US contrast imaging demonstrated that the boundaries of the prostate 

can be more clearly delineated, which might improve prostate contouring in 

patients. 

Conclusions: A novel 3D US imaging system allowed accurate daily dose 

assessment for prostate cancer. Novel applications such as contrast imaging 

open exciting venues for clinical applications. 

100 oral 

DOSIMETRIC OUTCOMES OF ADAPTIVE REPLANNING VERSUS 

DAILY TARGET-VOLUME CORRECTION IN PROSTATE 

D. Litzenberg 1 , K. Jee 1 , R. Ten Haken 1 , D. McShan 1 , B. Fraass 1 

1 UNIVERSITY OF MICHIGAN, Radiation Oncology, Ann Arbor MI, USA 

Purpose: To investigate the dosimetric benefit of daily pre-treatment correction 

versus a delivery outcome-driven replanning strategy in radiation therapy 

of the prostate. 

Materials: In 35 patients treated while using the Calypso Tracking System, 

daily pre-treatment target volume shifts from skin tattoos were determined, as 

was the mean of the intra-fraction motion. This data was used to simulate the 

dosimetric outcomes for patients planned using a 5 mm CTV to PTV margin 

in three scenarios. In each scenario, daily offsets were used to recalculated 

cumulative dose. It was assumed that the remaining fractions would be delivered 

as planned to estimate the final dose. The minimum dose to the CTV 

(prostate), and the mean dose to the rectum were used to assess dosimetric 

outcome. In the first scenario no corrections were made after setup to 

skin tattoos. This was calculated by shifting the planning CT to the initially 

measured position with setup to skin tattoos for each fraction. The replanning 

scenario was performed using a priority-based optimization technique. After 

each fraction the cumulative dose was calculated as in the first scenario, 

however, the deviation of a predetermined delivered dose criteria triggered reoptimization 

(e.g., the minimum PTV dose differs by > 4 Gy). In the example, 

a high priority was given to maintaining the minimum dose to the PTV at 78 

Gy while minimizing the mean rectum dose was addressed at lower level of 

priority, and replanning was performed four times. For the daily pre-treatment 

position correction scenario, the 3D mean offset due to intra-fraction motion 

was taken into account. 

Results: In general, not accounting for interfraction variation from setting up 

to tattoos leads to degradation of dosimetric goals. In the example, the minimum 

dose to the prostate, and mean dose to the rectum, are reduced by 

21.9% and 36.7% respectively. The replanning strategy generally attempts 

to restore dosimetric outcomes in the target volume, but may be sensitive to 

priorities and goals of the re-optimization in other volumes. In the example, 

the minimum dose to the prostate was reduced by only 2.9%, however mean 

dose to the rectum increased by 21.6%. The daily repositioning strategy generally 

maintained the dosimetric outcomes as originally planned by closely 

restoring the prostate to the planning CT geometry. In the example, the minimum 

dose to the prostate and mean dose to the rectum increased by 3.3% 

and 15.7% by consistently moving the volumes back to the high dose region. 

In this scenario, it appears that a smaller margin would have been beneficial. 

Conclusions: In the simulations performed here for large changes in internal 

target position, daily pre-treatment realignment to internal markers results 

in higher minimum dose to the CTV and lower mean dose to the rectum, 

compared to a sophisticated offline adaptive replanning technique, and with 

much less time and effort. 

101 oral 

S 33 

THE DOSE CONSEQUENCE OF ADAPTIVE IMRT FOR CERVIX 

CANCER: THE INFLUENCE OF TUMOR SIZE 

K. Lim 1 , V. Kelly 1 , J. Stewart 2 , X. Xie 1 , J. Moseley 2 , K. Brock 2 , Y. Cho 

2 , A. Fyles 1 , A. Lundin 3 , H. Rehbinder 3 , M. Milosevic 1 

1 PRINCESS MARGARET HOSPITAL; UNIVERSITY OF TORONTO, Radiation 

Medicine Program; Department of Radiation Oncology, Toronto, Canada 

2 PRINCESS MARGARET HOSPITAL; UNIVERSITY OF TORONTO, Radiation 

Medicine Program; Department of Radiation Physics, Toronto, Canada 

3 RAYSEARCH LABORATORIES AB, Stockholm, Sweden 

Purpose: Geographical miss due to tumor & organ mobility is a concern for 

cervix cancer IMRT. Overdosing of organs at risk (OAR) as tumor shrinks 

and normal tissues move into the high dose region is also possible. Tumor 

size may also influence such geometrical dynamics. Our hypothesis was that 

a mid-treatment replan would result in improved target coverage and OAR 

sparing compared to no replan, particularly for large tumors. We assessed 

the dose consequences of organ motion & tumor regression in these two 

IMRT scenarios. 

Materials: 30 pts with stage 1B-IVA cervix cancer, who underwent standard 

chemoRT & brachytherapy, had baseline & weekly MRI scans of the pelvis 

during treatment. The clinical target volume (CTV = GTV + cervix + parametria 

+ upper vagina + 2cm uterus) & OARs were contoured on the fused axial 

MR-CT images and on each weekly scan. Patient anatomy at each fraction 

was deformably mapped to the baseline case, allowing the dosimetric impact 

of inter-fraction motion to be modelled. Patients were dichotomised on 

median tumor volume (33cc). A PTV margin of 3mm (smallest limit of what 

might be clinically feasible in the setting of modern IGRT) was used as previous 

work by our group showed 5mm PTV margins to be adequate. Perfect 

daily image-guided set up to bone was assumed. Prescribed dose was 50Gy. 

CTV D98 >= 47.5Gy was considered acceptable. We compared dose to tumor 

& OARs for baseline plan, delivered plan (accumulated dose at the end of 

treatment, after organ motion has been accounted for) and replan (occurring 

mid-course and used for the remainder of treatment).


Results: There was a significant reduction in the delivered dose to the CTV 

relative to the planned dose in all patients, particularly in those with small tumors 

at diagnosis (p


distribution, the fluence profiles for different collimator settings and output factors 

free in air (called collimator factor, CF) are calculated. With the availability 

of an appropriate polyenergetic pencil beam kernel (PBK), and using convolution 

techniques, dose profiles and output factors (OF) for small fields can be 

modeled. This method offers an experimental alternative to the conventional 

dosimetry of small fields, where large uncertainties have been observed. 

Materials: The reconstruction is based on the measurement of strip integrals 

of the source. These are obtained by placing a radiation detector under a 

collimator assembly that limits its field of view to a very thin slit of the source 

of about 0.3 mm, hence, detecting radiation that comes from a small strip of 

the source. By moving the assembly and the detector at different positions 

and angular orientations with respect to the source, a set of strip integrals is 

obtained. The use of CT reconstruction techniques, with the set of strip integrals 

as input data, allows recovering information on size and shape of the 

source. The reconstruction is performed by establishing a linear equation system 

which relates the projection data to the unknown parameters (pixel values) 

that represent the reconstructed source; the equation system is solved 

using a least square minimization iterative algorithm.Direct applications of 

the source intensity distribution are the generation of fluence profiles and CF. 

When the geometry of the linac head is known, a simple integration of this 

source, limited by the different openings of the collimators and the position of 

the calculation point, can model the different relative fluence profiles and CF 

for small fields. Using convolution methods and the PBK this fluence profiles 

and CF can be converted into dose profiles and OF in water, respectively. 

Measurements were performed with a diode detector for field sizes up to 5x5 

cm. 

Results: Relative fluence profiles generated for squared fields using the reconstructed 

source distribution show deviations less than 2% and 2 mm when 

compared to the measured values. A good agreement between the CF measurements 

and calculation is also observed. Accuracy of the OF and dose 

profiles modeling will be discussed. 

Conclusions: An alternative method to the measurement of CF/OF in small 

fields is presented. The possibility of modeling fluence as well as dose profiles 

(once the PBK are available) in a simple approach, allows this method 

to be used as a supplemental periodical dosimetry check for the linac performance. 

105 oral 

PERFORMANCE OF THE RADPOS DOSE-POSITION VERIFICATION 

SYSTEM IN 4D RADIOTHERAPY USING A DEFORMABLE LUNG 

PHANTOM 

J. Cygler 1 , A. Cherpak 2 , S. Monica 3 , S. Jan 4 

1 

THE OTTAWA HOSPITAL CANCER CENTRE, Medical Physics, Ottawa, 

Canada 

2 

CARLETON UNIVERSITY, Physics, Ottawa, Canada 

3 

MAISONNEUVE-ROSEMONT HOSPITAL, Medical Physics, Montréal, Canada 

4 

MCGILL UNIVERSITY, Medical Physics, Montreal, Canada 

Purpose: Measurement and minimization of the impact of respiratory motion 

in imaging, treatment planning and delivery require a quantitative means of 

verification of both dose and position in a reproducible setup involving periodic 

motion and deformation. With the recent increase in applications of image 

guided radiation therapy, the verification of different aspects of the 4D radiotherapy 

involving breathing motion is critical. The purpose of our work was 

to use the novel dose-position measuring system, RADPOS, in conjunction 

with a deformable lung phantom to quantitatively verify planning and delivery 

stages of 4D radiotherapy. 

Materials: RADPOS probes, consisting of a MOSFET dosimeter combined 

with an electromagnetic positioning sensor were placed inside the deformable 

lung phantom containing a tumour made of tissue equivalent material: one 

detector inside and the other outside the tumour, inside the lung portion of the 

phantom. CT scans were taken with the phantom in three breathing phases, 

end of inhale (EOI), middle of inhale (MOI), and end of exhale (EOE). The 

detector position inside the phantom was read with the RADPOS software 

and compared to the position determined from the CT data. A three-beam 

conformal treatment plan was created using as "planning dataset" the CT image 

of the phantom in the EOE phase, with the two detectors at the positions 

described above. Superposition algorithm with inhomogeneity corrections on 

(XiO TPS) was used to calculate the dose distribution. The breathing cycle 

was divided into two states, EOE and EOI. The same treatment was delivered 

twice, with the phantom in the EOE and in the EOI phases. RADPOS measured 

doses during both irradiations were compared to the treatment plan 

calculated values. 

Results: The detector displacements measured by the RADPOS system 

were within 1.4 mm, -0.1 mm, and 1.5 mm of measurements from the CT images 

for movement between the EOE and EOI, EOI and MOI, and MOI and 

EOE phases, respectively. There was no trend in the differences in RADPOSmeasured 

and calculated doses for individual beams and breathing states, 

with a maximum deviation of 3.52 cGy (2.2% of total dose) for the detector 

inside the tumour and 4.66 cGy (4.2% of the total dose) for the detector in the 

lung tissue. 

Conclusions: Our results indicate that RADPOS combined with deformable 

lung phantom can be a useful tool for quality assurance in 4D treatment delivery. 

Acknowledgements: This project was partially supported by an operating 

S 35 

grant from the Canadian Inst. of Health Research #MOP 79448 and a grant 

from The Health Technology Exchange (HTX). 

106 oral 

LUNG DOSE CALCULATIONS FOR BREAST TREATMENT: IMPACT 

OF DOSE CALCULATION ALGORITHMS IN DIFFERENT RESPIRA- 

TORY PHASES 

E. Vanetti de’ Palma 1 , A. Fogliata 1 , G. Nicolini 1 , A. Clivio 1 , P. Winkler 2 , 

L. Cozzi 1 


2 UNIVERSITY HOSPITAL GRAZ, Medical Physics, Graz, Austria 

Purpose: To investigate the influence of different air filling in lungs on the calculation 

accuracy of photon dose algorithms and to identify potential patterns 

of failure with clinical implications. 

Materials: Selected respiratory phases were free breathing (FB) and deep inspiration 

breath hold (DIBH). Algorithms investigated were the standard pencil 

beam (PBC), the Anisotropic Analytical Algorithm (AAA) and the Collapsed 

Cone (CC) from the Varian Eclipse or Philips Pinnacle treatment planning systems. 

Algorithms were compared against the Voxel Monte Carlo (VMC++). 

Analysis was performed in terms of physical quantities inspecting either dose 

volume or dose mass histograms and in terms of an extension to three dimension 

of the gamma index of Low. 

Results: Collectives acquired in FB or DIBH showed well separated average 

lung density distributions with mean density of 0.27±0.04 and 0.16±0.02 

g/cm3 respectively, and average peak density of 0.17±0.03 and 0.09±0.02 

g/cm3. Analysis of volume- or mass- dose histograms proved the expected 

deviations on PBC results due to the missing lateral transport of electrons with 

underestimations in the low dose region and overestimations in the high dose 

region. More complicate patterns were observed for CC and AAA. From the 

gamma analysis it resulted that PBC is systematically defective compared to 

VMC++ over the entire range of lung densities and dose levels with severe violations 

in both respiratory phases. The fraction of lung voxels with gamma>1 

for PBC reached 25% in DIBH and about 15% in FB. CC and AAA performed, 

on the contrary, similarly and with fractions of lung voxels with gamma>1 in 

average inferior to 2% in FB and 4-5% (AAA) or 6-8% (CC) in DIBH. 

Conclusions: PBC proved to be defective in calculations involving lungs and 

particularly for cases where specific respiratory phases (e.g. DIBH) are assumed 

for treatment. CC and AAA manifested a good to excellent degree 

of consistency against Monte Carlo simulations and provided stable results 

over the entire range of clinically relevant densities. Defective were in practice 

confined to small density ranges peaked around 0.05 g/cm3, well below 

observed mean and peak distributions of real lungs. 

107 oral 

PREDICTING SMALL PHOTON FIELD DOSIMETRY WITH A MONTE 

CARLO MODEL 

A. Scott 1 , A. E. Nahum 1 , J. Fenwick 1 

1 CLATTERBRIDGE CENTRE FOR ONCOLOGY (CCO), Physics Department, 

Wirral, United Kingdom 

Purpose: Accurate characterisation of small-field dosimetry requires measurements 

to be made with precisely aligned, specialised detectors and is 

thus time-consuming and error-prone. This work concerns measurement differences 

between detectors by using a Monte Carlo model matched to largefield 

data to predict properties of smaller fields. Measurements made with 

a variety of detectors have been compared with calculated results to assess 

their validity and explore reasons for differences. Electron diodes are expected 

to produce some of the most useful data, as their small sensitive cross 

sections give good resolution whilst their energy dependence is shown to vary 

little with depth and field size for a 15 MV linac beam. 

Materials: BEAMnrc has been used to create a model of a 15MV beam from 

a Varian 2100C by matching to dosimetric data for square fields larger than 

3 cm measured with a variety of detectors. High resolution voxels (0.5 mm 

x 0.5 mm x 2 mm) were used in the penumbral region whilst 2 mm cubical 

voxels were used on the central axis. 

Results: The model produces small-field profiles and percentage depth 

doses (PDD) that agree well with electron diode data for field sizes down 

to 0.5 cm. Larger detectors including the pinpoint chamber and a diamond 

are seen to broaden the penumbra at all field sizes and increase the PDD for 

fields sizes below 2 cm due to divergence. Whilst, for fields sizes of 1.5 

cm and above, little detector-to-detector variation exists in measured output 

factors, a relative spread of 17.8% is seen for a 0.5cm field. Although 

good agreement is obtained between output factors calculated with the Monte 

Carlo model and those measured with the electron diode for fields 1.5cm and 

above, the MC value is 6% low for the smallest 0.5cm field. Further modelling 

suggests this discrepancy can be resolved with a small reduction in the focal 

spot size. Data will be presented to show the sensitivity of the calculated 

penumbra and output factor to focal spot size. 

Conclusions: We have shown that the large-field Monte Carlo model can 

be used to predict small-field profiles and PDDs measured with an electron


diode. However, the output factors for the smallest fields depend significantly 

on the size of the focal spot and so a highly accurate penumbra match is 

required. 

108 oral 

TWO CENTRE INVESTIGATION INTO APPARENT ENERGY DEPEN- 

DENCE OF GAFCHROMIC EBT FILM 

C. Fletcher 1 , A. McCabe 2 , A. Morgan 3 , J. Verney 1 , D. Thwaites 2 

1 UNIVERSITY HOSPITAL, COVENTRY, Department of Clinical Physics and 

Bioengineering, Coventry, United Kingdom 

2 ST JAMES’S INSTITUTE OF ONCOLOGY, Department of Medical Physics 

and Engineering, Leeds, United Kingdom 

3 ST JAMES’S INSTITUTE OF ONCOLOGY, Medical Physics, Leeds, United 

Kingdom 

Purpose: GafChromic EBT film is reported to have a near energy independent 

response. However, independent studies at St James’s Institute of Oncology, 

Leeds and University Hospital Coventry have both shown differences 

between the dose responses of EBT at MV and kV energies 

Materials: Coventry: The dose response of GafChromic EBT was investigated 

for 100kV (2.06mm Al HVL), 250kV (1.94mm Cu HVL), 6MV and 25MV 

photons and 4MeV and 20MeV electrons for doses between 0 and 10Gy. 

Films were exposed on the surface of a WTe solid water phantom for kV 

energies and at dmax for MV energies. 100kV films were exposed using a 

3cm diameter applicator (30cm FSD) and 250kV films using a 10cm diameter 

applicator (50cm FSD). MV films were exposed using a 10cm by 10cm 

field (100cm SSD for photons, 95cm SSD for electrons). Films were digitised 

using a Vidar white light scanner with a 16bit scanning resolution. Optical 

density was calculated from film intensities obtained using PTW MePhysTo 

mc2. 

Leeds: The dose response of GafChromic EBT film was investigated for photon 

energies of 80kV (2.7mm Al HVL), 6MV and 10MV. For MV energies, 

measurements were performed by exposing the film isocentrically in a WTe 

phantom at a depth of 5cm using a 10cm x 10cm field size. For 80kV, film was 

exposed on the surface of a WT1 phantom using a 5cm diameter applicator 

(20cm FSD). Films were digitised using an Epson Expression 1680 flatbed 

colour scanner in 48bit mode. Software written in Matlab was used to extract 

the 16bit red channel and correct the images for the non-uniform response 

of the scanner . A non-linear least squares curve fitting routine was used to 

construct a calibration curve. 

Results: Measurements at both centres showed similar energy dependency, 

figure 1.A response for 2Gy exposures of EBT at 100kV of 0.930 relative to 

the response at 6MV has been reported. However, at Coventry, response 

relative to 6MV of 0.742 + 1.6% was found for 100kV and 0.855 + 1.6% for 

250kV and at Leeds a relative response of 0.776 + 1.2% was found for 80kV 

relative to 6MV. 

Figure 1: Calibration curves for GafChromic EBT measured using a 

range of different energies at Leeds and Coventry 

Conclusions: Two independent studies have observed similar magnitudes 

of differences between the dose responses of EBT at MV and kV energies, 

contrary to the response reported in the literature. Further work is required to 

verify this apparent energy dependence and to identify possible causes. 

109 oral 

QUALITY ASSURANCE OF DOSIMETRY IN UK CENTRES PARTIC- 

IPATING IN THE IMPORT LOW PARTIAL BREAST RADIOTHERAPY 

TRIAL 

L. Ciurlionis 1 , Y. Tsang 1 

1 MOUNT VERNON HOSPITAL, Clinical Physics, Northwood Middlesex, 


Purpose: IMPORT (Intensity Modulated Partial Organ RadioTherapy) LOW 

is a multi-centre, randomised trial which tests whether partial breast radiotherapy 

is as effective and less damaging than whole breast radiotherapy in 

low risk, early stage breast cancer. As part of the trial’s quality assurance 

program dosimetry measurements have been performed at 17 collaborating 

radiotherapy centres to ensure consistent treatment between centres and to 

examine the ability of treatment planning systems (TPS) to calculate the dose 

to the breast correctly. 

Materials: Preliminary measurements were made testing the ability of the 

planning system to model small MLC shapes in a simple square phantom. 

A custom-made breast phantom was constructed and a full CT dataset was 

made available to each centre. Plans were prepared in accordance with the 

IMPORT LOW trial protocol, and measurements were performed across the 

treatment volume with an ionisation chamber in the breast phantom. Data 

was analysed from 9 different TPS’s, 3 linac manufacturers, and 5 photon 

energies ranging from 6MV 18MV. 

Results: Dose points measured in the centre of the small MLC shapes were 

within 3% of the TPS dose in 16 out of 17 centres (range 2.5% - 2.3%). 

13 out of 17 centres used simple manual segments to achieve the required 

dose homogeneity in the breast phantom plan, 3 inverse-planned IMRT and 1 

used physical compensators. An average of 6 fields were used to achieve the 

IMPORT LOW planning aims (range 4 9). The mean discrepancy between 

measured and calculated dose for all points of interest was less than 3% for 

each centre. Dose measured in the centre of the partial breast volume was 

within 2.5% of the TPS dose for all centres (mean 0.7%, range -2.5% - 1.0%). 

Mean dose close to the apex of the breast, within 2cm of the skin surface, 

was measured to be within 0.6% of calculated (range 2.8% - 2.5%). Dose to 

a point within 2cm of the lung was measured lower than predicted by 15 out 

of 17 centres (mean 2.1%, range 5.1% - 0.6%). 

Conclusions: Dosimetry measurements have provided confidence that participants 

in the IMPORT LOW trial will deliver treatment with an acceptable 

degree of consistency between centres, despite variations in TPS, planning 

technique and beam energy. Modern TPS algorithms can accurately predict 

dose across the breast volume in complex planning situations, including areas 

close to missing tissue and inhomogeneities.

MONDAY, SEPTEMBER 15, 2008 DEBATE 

Debate 

The house believes that IGRT is the treatment of 

choice for T2 prostate carcinoma in a 60 y old man 

110 speaker 

THIS HOUSE BELIEVES THAT IGRT IS THE TREATMENT OF 

CHOICE FOR T2 PROSTATE CARCINOMA IN 60 YEARS OLD MEN. 

G. Kovács 1 

1 UNIVERSITY OF LÜBECK, Radiation Oncology, Lübeck, Germany 

Counterpoint:T-stage is the less relevant risk factor in comparing it to the 

role of initial PSA and Gleason score. Therefore, for better understanding, 

it is better to compare treatment results of low-, intermediate- and high risk 

groups, where the risk definition should be described by at least three factors 

(iPSA, Gleason score, T-stage). However, there are many evidences 

in the literature showing the clear advantage of local radiation dose escalation 

in improving the results of radiotherapy in locally advanced prostate cancer. 

Analysis of single institutional dose escalation trials by external beam 

(EBRT) or combined EBRT+ Brachytherapy (BT) -both seeds or remote stepping 

sources- showed, that the improvement in outcome by escalating the 

dose reach the plateau at approximately 85-95 Gy total dose. Modern radiation 

therapy technology like IMRT or IGRT- allows the application of this high 

local dose with acceptable early and late toxicity. However, if we compare different 

dose escalation modalities, there are major differences between IGRT 

and BT technology in quality of boost target definition, inter- and intrafraction 

target movements, target dose painting, volume of normal tissue low 

dose areas, total treatment time as well in organ at risk (OAR) doses.Target 

definition: IGRT commonly uses CT images for target definition purposes 

compared to transrectal ultrasound (TRUS) used at brachytherapy. TRUS is 

more eligible for local definition of the anatomy. Additionally, in BT there is 

no need for security zones around of the prostate (PTV=CTV).Interfraction 

target movements: IGRT technology reduces the influence of interfraction 

movements; however, this type of movement does not exist in brachytherapy.Intrafraction 

target movements: by using 4D technology and IGRT the 

negative influence of target movements can be minimized, but it do not exist 

in interstitial brachytherapy.Target dose painting: IGRT together with 4D technology 

offers the possibility of dose painting; however, the use of remote stepping 

source technology offers higher dose gradients within the target.Volume 

of low dose area: IGRT can not avoid the irradiation of large normal tissue 

volumes with lower dose. The avoidance of low doses in normal tissues is 

important in a 60 years old man, since nowadays he has the potential to 

live additional 20 years. The steep dose fall-off of BT sources avoids normal 

tissue radiation.Dose on OARs: There is no better method of keeping 

the OAR dose low, than using BT sources with steep dose fall-off.Total treatment 

time: the application of doses >80 Gy is at least two weeks shorter by 

EBRT+BTIn summary, if we compare the potential of IGRT alone versus any 

kind of EBRT+ BT boost in local dose escalated prostate radiotherapy, there 

are many factors supporting EBRT+ BT as the treatment of choice. 

111 speaker 

IN FAVOUR OF THE MOTION 

G. De Meerleer 1 , V. Fonteyne 1 , G. Soete 2 

1 GHENT UNIVERSITY HOSPITAL, Radiotherapy, Gent, Belgium 

2 AZ VUB, Radiotherapy, Brussels, Belgium 

The house believes that image guided radiotherapy is the treatment of choice 

for T2 prostate carcinoma in a 60 year old man: will the urologists finally take 

radiotherapy into account when decision has to be made? 

In case of localized prostate cancer, several randomized trial have 

demonstrated significantly better biochemical control rates with increased 

dose (1-5). An improved local control also improves the metastasis-free 

survival (5) Modern technology such as intensity-modulated radiotherapy 

(IMRT) or conformal arc therapy allow dose escalation at a low level of late 

gastro-intestinal (GI) and genito-urinary (GU) toxicity. But after all, what are 

the exact data, and is the radiation oncologist finally in the position to stand 

up for his/her rights and the right of the "T2 prostate cancer patient" to have 

access to modern radiotherapy? 

With a NID2 varying from 76 Gy to 83 Gy and using IMRT or conformal arc 

therapy, biochemical control at 3, 5 and 7 years is obtained in 86-94% (6-9), 

85-92% (7, 10) and 72-90% (11). The argument that these high doses are 

accompanied by a not-tolerable increase in toxicity is nonsense, at least 

when modern radiotherapy techniques are considered. 

Modern series have reported 6% grade ≥2 late GI toxicity with a median 

time to development of 17 months (12). Grade 3 rectal bleeding, still 

considered as the most important toxicity by many physicians occurs only 

in 1-3% of the patients (7, 12, 13). Moreover, 91% of the late grade ≥2 GI 

toxicity resolves with time (12). IMRT clearly reduces the actuarial likelihood 

of developing late grade ≥2 GI toxicity at 10 years from 13 to 5% (p80 % (12). For 

both late GI and GU toxicity, there is a clear relationship with acute GI and 

S 37 

GU toxicity respectively. 

The criticism that external-beam radiotherapy takes several weeks is of 

course correct when normal fractionation schedules are used. However, in 

view of the low α/β ratio of prostate cancer, hypofractionation schedules 

have been used more frequently providing similar results concerning 

biochemical control and toxicity except for urgency of defecation (14). 

Further improvements of image guided radiotherapy include dose focusing 

on the MR-detected intraprostatic lesion (15) and efforts to reduce the risk of 

developing secondary malignancies. 

Anno 2008, no patient with a T2 prostate cancer should be hidden from the 

opportunity of having image-guided radiotherapy. Biochemical outcomes are 

excellent and at least comparable with those of radical prostatectomy. Late 

toxicity is low. Other than scientific reasons should not play a role in decision 

making. 

References: 

1. Zietman et al. JAMA 2005; 294: 1231-1239. 

2. Peeters et al. J Clin Oncol 2006; 24: 1990-1996. 

3. Dearnaley et al. Lancet Oncol 2007; 8: 475-478. 

4. Kuban et al. Int J Radiat Oncol Biol Phys 2008; 70: 67-74. 

5. Pollack et al. J Clin Oncol 2000; 18: 3904-3911. 

6. Zelefsky et al. Int J Radiat Oncol Biol Phys 2002; 53: 1111-1116. 

7. Vora et al. Int J Radiat Oncol Biol Phys 2007; 68: 1053-1058. 

8. De Meerleer et al. Radiother Oncol 2007; 82: 160-166. 

9. Soete et al. Personnal communication. 

10.Cahlon et al. Int J Radiat Oncol Biol Phys 2008; In Press. 

11.Zelefsky et al. Int J Radiat Oncol Biol Phys 2008; In Press. 

12.Zelefskyt et al. Int J Radiat Oncol Biol Phys 2008; 70: 1124-1129. 

13.Jereczek-Fossa et al. Int J Radiat Oncol Biol Phys 2008; In Press. 

14. Yeoh et al. Int J Radiat Oncol Biol Phys 2006; 66: 1072-1083. 

15. Fonteyne et al. Int J Radiat Oncol Biol Phys 2008; In Press. 

112 speaker 

IN FAVOUR OF THE MOTION 

D. Boehmer 1 

1 CHARITÉ CAMPUS VIRCHOW KLINIKUM, Berlin, Germany 


113 speaker 

AGAINST THE MOTION 

P. A. Abrahamsson 1 

1 MALMÖ UNIVERSITY HOSPITAL, Malmö, Sweden 




Clinical Lung 

114 oral 

PATTERNS OF PRACTICE SURVEY FOR RADIATION THERAPY IN 

LUNG CANCER AMONG ESTRO MEMBERS 

J. Widder 1 , D. De Ruysscher 2 , S. Senan 3 , B. Movsas 4 , H. Sandler 5 , J. 

Langendijk 1 , F. M. Kong 6 

1 

UNIVERSITY MEDICAL CENTRE GRONINGEN, Radiotherapy, Groningen, 

Netherlands 

2 

UNIVERSITY MEDICAL CENTRE MAASTRICHT, MAASTRO, GROW, 

Maastricht, Netherlands 

3 

FREE UNIVERSITY MEDICAL CENTRE, Radiotherapy, Amsterdam, 

Netherlands 

4 

HENRY FORD HOSPITAL, Radiation Oncology, Detroit, USA 

5 

UNIVERSITY OF MICHIGAN, Radiation Oncology, Ann Arbor MI, USA 

6 

VETERANS AFFAIRS ANN ARBOR HEALTHCARE SYSTEM/UNIVERSITY OF 

MICHIGAN, Radiation Oncology, Ann Arbor, USA 

Purpose: To investigate current patterns of practice in treatment of NSCLC 

and SCLC among ESTRO members. 

Materials: ESTRO members (n ~4500) received a 35-item questionnaire by 

e-mail in June 2007, which was designed by a panel of ASTRO radiation oncologists. 

Results from the US were presented at ASCO 2007. Respondents 

were asked about treatment of patients who were recently seen in their practice. 

Questions addressed treatment strategy, and radiotherapy planning and 

delivery. Results are reported descriptively and correlations with indicators 

for expertise were tested using Pearson’s chi-square test. 

Results: A total of 590 of 603 responses received were evaluable (overall 

response rate 13%). Peripheral stage I NSCLC in medically inoperable patients 

was treated using conventional RT by choice by 33% of respondents, 

with stereotactic RT (SRT) by 23%, and with conventional RT due to the unavailability 

of SRT by 35%, respectively. Thus, 58% treated or would like 

to treat those patients with SRT. For a central stage I NSCLC, 63% of the 

respondents chose conventional RT, 9% treated with SRT, and 34% would 

prefer SRT. Medically inoperable patients with NSCLC cT2N1 received combined 

chemotherapy with RT (CRT) by 86% of respondents, stage III NSCLC 

patients with a good performance score received CRT from 98%, treatment 

was delivered concurrently by 76%. A stage III patient with poor performance 

status was treated with RT alone by 43%, 42% gave some CRT combination. 

In SCLC LD, 75% of respondents administered early RT, but 50% would 

have liked to commence RT with the 1st cycle had logistics permitted this. 

Elective nodal irradiation (ENI) is omitted in NSCLC by 44% of respondents, 

and in SCLC by 27%, respectively. Only 38% of the respondents were content 

with radiotherapy planning using rapid CT scans acquired during quiet 

(uncoached) respiration, while 57% used or would like to use a motion management 

strategy. Responses did not correlate with years since qualification 

as radiation oncologists (+/- 10 years), but highly significant differences were 

recorded between respondents specialising in thoracic oncology (n=152) versus 

non-specialists (n=378) (p=0.003 p 50 %, MLD=15 Gy when FeV1 and/ or DLCO 40-49 

%, MLD=10 Gy when FeV1 and/or DLCO < 40 %. Other dose-constraints: 

spinal cord max: 54 Gy, brachial plexus (Dmax): 66 Gy. Minimum tumor dose: 

54 Gy. Maximal dose: 79.2 Gy. Radiation doses were specified according to


ICRU 50. Radiotherapy was delivered in twice-daily fractions of 1.8 Gy, with 

8 h to 10 h as interfraction-interval, 5 days per week. Primary endpoint: overall 

survival. Secondary endpoints: progression-free survival (PFS), dyspnea 

(CTCAE 3.0), dysphagia (CTCAE 3.0). Analysis was performed on March 

10, 2008. The trial was approved by the required authorities; all patients 

gave informed consent. 

Results: 196 patients were included: 139 males, 57 females. The median 

age (+/- SD, range) was 68.3 +/- 10.5 years (42-88); WHO PS 0 19 %, 1 55 

%, 2 26 %; median FeV1 92.6 +/- 19.5 %; DLCO 60.9 +/- 20.5 %; stage: I 26 

%, II 14 %, IIIA 23 %, IIIB 37 %; squamous cell 28 %, adenocarcinoma 10 

%, large cell 30 %, NSCLC NOS 32 %. The median radiation dose was 63.1 

+/- 13.9 Gy (5.4-79.2), delivered in 34.8 +/- 8.5 fractions (3-44) in a median 

overall treatment time of 25.5 +/- 7.2 days (1-69). The median MLD was 13.6 

+/- 4.5 Gy (2.4-19.9). The median follow-up was 17.1 +/- 4.6 months (10-28). 

Toxicity: Esophagus: grade 0: 43%, 1: 34%, 2: 19%, 3: 5%; all reversible 

within 3 weeks post-treatment. Max dyspnea: grade 0: 21%, 1: 40%, 2: 24%, 

3: 12%, 4: 3%, 5: 1% (1 patient). Important (grade 2 or more) lung toxicity 

was observed in 15% (95 % CI 10-20) of the patients. No Grade 2 or higher 

dermatitis was observed during or after radiotherapy. Median survival was: 

for stage I: 22 months (95 % CI 16-27), stage II: 15 months (95 % CI 7-24), 

stage IIIA: 18 months (95 % CI 9-26) and stage IIIB: 15 months (95 % CI 

7-23). 

Conclusions: Individualized radiotherapy according to the MLD yields toxicity 

as expected from our in silico and phase I trials. Survival is similar to 

concurrent chemo-radiation schedules, but longer follow-up and randomized 

comparisons are needed. 

117 oral 

STEREOTACTIC BODY RADIOTHERAPY FOR MEDICALLY INOP- 

ERABLE STAGE I NON-SMALL CELL LUNG CANCER: MATURE 

OUTCOME AND TOXICITY RESULTS 

N. Kopek 1 , M. Paludan 1 , J. Petersen 2 , C. Grau 1 , M. Høyer 1 

1 AARHUS UNIVERSITY HOSPITAL, Oncology, Aarhus C, Denmark 

2 AARHUS UNIVERSITY HOSPITAL, Medical Physics, Aarhus C, Denmark 

Purpose: To report the mature outcome and toxicity results of stereotactic 

body radiotherapy (SBRT) in the treatment of medically inoperable patients 

with primary stage I NSCLC at the Aarhus University Hospital. 

Materials: Between 2000 and 2007, 89 consecutive patients were treated by 

linac-based SBRT using a body frame. Forty-five gray in three fractions (BED 

112.5 Gy) over one week prescribed to the isocentre (67% isodose covering 

PTV) was given until 2004 when 67.5 Gy in 3 fractions (BED 219.4 Gy) 

was introduced for non-centrally located lesions. Forty-six percent of patients 

were under protocol while the remainder were retrospectively reviewed. 

Results: With a median follow-up of 44 months, 5 patients developed local 

failure. The local control rate at 4 years was 89% while the freedom-fromfailure 

was 36%. The 2-,3- and 5-year cancer specific survival was 72%, 64% 

and 50% respectively, with a median of 61 months. The median overall survival 

was 22 months. No significant differences in control or survival rates 

were observed between dose schedules. Seventy-eight percent of all worst 

toxicity grade scores were grade 0 or represented no change from baseline. 

Of all toxicities above baseline, the most frequent was asymptomatic pulmonary 

fibrosis (20.4%), followed by worsening of performance status (14%) 

and dyspnea (11.7%). Most toxicity was grade 1 (67.9%) with 14% grade 

3/4. This profile was consistent during both the acute/subacute and late onset 

periods, with the exception of the most frequent toxicity: asymptomatic 

pneumonitis dominated the subacute period progressing to fibrosis in the late 

period. No significant difference in the toxicity profiles was observed between 

dose schedules. 

Conclusions: Longer follow-up confirms the excellent local control and encouraging 

survival outcomes of SBRT for inoperable early stage NSCLC. The 

late toxicity is characterized by radiographic changes and decline in lung function/PS. 

No significant gain in control with a BED > 112.5 Gy was observed 

and therefore use of a lower dose/fraction schedule for centrally located lesions 

is recommended. SBRT is now the standard of care for inoperable 

stage I NSCLC at Aarhus University Hospital. A Scandinavian randomized 

trial is presently recruiting to formally compare SBRT with conventionally fractionated 

radiotherapy. 

118 oral 

DETERMINATION OF A VOXEL CONTROL PROBABILITY; A QUAN- 

TITATIVE RELATION BETWEEN FDG UPTAKE IN THE TUMOR, 

DOSE AND TUMOR CONTROL TO GUIDE TUMOR DOSE REDISTRI- 

BUTION IN NON-SMALL CELL LUNG CANCER (NSCLC) 

S. Petit 1 , H. Aerts 1 , C. Offermann 1 , M. Oellers 1 , P. Lambin 1 , D. De 

Ruysscher 1 , A. Dekker 1 

1 GROW - SCHOOL FOR ONCOLOGY AND DEVELOPMENTAL BIOLOGY, 

MAASTRICHT UNIVERSITY MEDI, Department of Radiation Oncology 

(MAASTRO), Maastricht, Netherlands 

Purpose: Purpose: Local tumor failure still occurs in the overwhelming major- 

S 39 

ity of locally advanced NSCLC patients treated with (chemo)radiation. There 

are strong indications that treatment efficacy can be improved by redistributing 

dose from radio-sensitive to radio-resistant tumor regions without increasing 

the dose to normal tissue. We have shown previously (abstract Aerts et 

al.) that the likelihood of residual disease 3 months after therapy is largest 

in the regions that correspond to high fluorine-18 deoxyglucose (FDG) uptake 

zones in the primary tumor before the start of therapy. This observation 

makes FDG uptake a potential target for tumor dose redistribution. Our objective 

is to derive a voxel control probability, i.e. a quantitative relation between 

FDG uptake in a voxel before the start of radiotherapy, delivered dose to the 

voxel and the probability of residual disease in that voxel 3 months after therapy 

in order to guide tumor dose redistribution. 

Materials: Materials and Methods: 95 patients with inoperable NSCLC (stage 

I-III) that were treated with radical radiotherapy alone or with chemo-radiation 

were analyzed. FDG PET-CT scans were acquired just before the start of radiotherapy 

(day 0) and three months post-treatment. The total radiation dose 

varied between 54 and 80 Gy. The PET scans of each patient before and 

after therapy were registered using an automatic rigid registration based on 

bony landmarks in the proximity of the primary tumor using the CT scans. Tumors 

with large deformations, as determined by two independent observers, 

were excluded from the analysis. The residual disease of the primary tumor 

after therapy was defined as the voxels (size 5x5x5 mm3) with a FDG uptake 

higher than the maximum uptake in the aortic arch. The probability of 

residual disease in a tumor voxel as function of its SUV at day 0 (SUV0) is 

determined for each tumor by scoring the portion of voxels within predefined 

SUV bandwidths that contain residual disease after therapy. 

Results: Preliminary Results: 4 patients were excluded because of large 

deformations of the tumor. 24 patients had a residual 3 months after therapy, 

of which 11 have been analyzed so far. Below an SUV0 of 5 the probability 

of residual disease increases with increasing SUV0 for each patient. The 

maximum probability occurred at an SUV of 8. For SUV0 > 10 the probability 

decreased, but only three patients had FDG uptake values above this level. 

A strong inter-patient dependence on the probability of residual disease was 

observed. 

Conclusions: Conclusion :The probability of residual disease in a tumor 

voxel depends on its SUV before therapy. The large variation between different 

patients was expected and is thought to arise from differences in delivered 

dose, tumor volume and integral SUV uptake. The influence of these 

parameters on the probability of residual disease is studied and results will 

be presented at the conference. 

119 oral 

THE CHOICE OF A SPECIFIC 4D-DATASET FOR LUNG CANCER 

TREATMENT PLANNING DOES NOT AFFECT THE PNEUMONITIS 

RISK ASSESMENT 

M. van de Pol 1 , H. Sandra 1 , W. de Kruijf 1 

1 DR BERNARD VERBEETEN INSTITUUT, Tilburg, Netherlands 

Purpose: To reduce the uncertainties and artifacts caused by respiratory 

motion during CT scanning, 4D-CT data sets containing 3D CT images at 

multiple phases of the respiratory cycle are being used for lung cancer treatment 

planning. The purpose of this study is to evaluate the implications of the 

choice of a specific dataset for treatment planning focussing on lung volume 

variation and DVH-values used for predicting the chance of radiation pneumonitis. 

Materials: 4D-Computed tomography (4D-CT) scans were obtained for 27 

patients with stage I-III non-small cell lung cancer. These scans were performed 

on a LightSpeed RT CT scanner (GE Medical Systems) during quiet 

uncoached respiration. During the scanning procedure, respiratory signals 

are recorded using the Varian RPM respiratory monitoring hardware. Using 

Advantage 4D (GE Medical Systems) each CT image was sorted into 1 of 10 

"bins" corresponding to the respiratory phase at which the image was captured. 

Both lungs were contoured using the built-in segmentation algorithms 

of Advantage Sim MD (GE Medical Systems). XIO (CMS) performed the dose 

calculations providing similar target coverage on the following bins: the average 

intensity projection (AvIP), the phase bin corresponding with the largest 

volume (in all cases the 0% phase), and in the phase bin corresponding with 

the smallest volume (the 50-60% phase). The prescribed dose was 3 times 

18 Gy on the surrounding 80% isodose line in 13 patients with stage I disease 

and 24 times 2.75 Gy according to the ICRU-62 guidelines in 14 patients with 

stage III disease. The following dosimetric parameters were generated from 

the DVH: mean lung dose (MLD), lung-volume receiving at least 20 Gy (V20), 

lung-volume receiving at least 5 Gy (V5). Based on these parameters, the 

risk for radiation pneumonitis was assessed. 

Results: The mean variation in pulmonary volume within a patient is 13.2% 

(range 4.4-43.2%). This results in a mean variation of the absolute value 

of the V20 of 1.3% (range 0.0-3.7%), of the V5 of 2.2% (range -1.3 5.3) 

and of the MLD of 77cGy (range 8 -211cGy). In all but one patient, DVHparameters 

were lowest, when calculated on the phase bin with the maximum 

pulmonary volume (phase 0). Dose calculations on the AvIP result in values 

for the DVH parameters between those for calculations on the maximum and 

minimum lung volume. The differences in DVH parameter values do not lead 

to changes in the estimated pneumonitis risk using the Graham risk profile 

(IJROBP 1999: 45; 323-9).


Conclusions: Changes in pulmonary volume, as seen in quiet respiration 

during 4D-CT-acquisition, do not result in a clinically relevant variation in DVH 

values. Therefore, the selected phase in treatment planning to determine 

DVH-parameters seems to be clinically irrelevant. 

BT Physics 

120 oral 

BROAD BEAM TRANSMISSION DATA FOR THE SHIELDING OF 

BRACHYTHERAPY FACILITIES* 

J. Venselaar 1 , F. Ballester 2 , D. Baltas 3 , J. Gimeno 4 , D. Granero 5 , P. 

Papagiannis 6 , J. Perez-Calatayud 5 

1 

DR. B. VERBEETEN INSTITUTE, Department of Clinical Physics, Tilburg, 

Netherlands 

2 

UNIVERSITY OF VALENCIA-IFIC, Valencia, Spain 

3 

KLINIKUM OFFENBACH GMBH, Department of Engineering and Medical 

Physics, Offenbach am Main, Germany 

4 

IVO, Radiation Oncology, Valencia, Spain 

5 

LA FE UNIVERSITY HOSPITAL, Radiation Oncology, Valencia, Spain 

6 

ATHENS UNIVERSITY, MEDICAL SCHOOL, Laboratory of Medical Physics, 

Athens, Greece 

Purpose: To arrive at a validated, self-consistent, data set for brachytherapy 

facility shielding that addresses the variation of corresponding results in the 

literature due to the diversity of methods and assumptions used, and present 

it in a form appropriate to facilitate the accurate design or modification of 

facilities in view of the recent changes in popularity and delivery technology 

in brachytherapy. 

Materials: The GEANT4 Monte Carlo simulation code was used to calculate 

broad beam transmission curves of Co-60, Cs-137, Ir-192, Yb-169, I- 

125 and Pd-103, through materials of interest for structural shielding (stainless 

steel, lead, leaded glass, ordinary and barite concrete). Primary photon 

spectra were taken by the NuDat 2 software (National Nuclear Data 

Center, Brookhaven National Laboratory). Photon emissions of energy less 

than 10keV were suppressed and bare point sources were simulated for 

each radionuclide/material combination in a geometry chosen to represent 

brachytherapy facilities in terms of dimensions without taking into account the 

photon build up originating from inside the room. Density and percentage 

elemental composition of the simulated shielding materials were taken from 

the Physical Reference Data server of the National Institute of Standards and 

Technology. The MCNPX code was also used independently for the partial 

validation of results. 

Results: Broad beam transmission data for each radionuclide/material combination 

are presented and compared to results derived from literature in the 

form of the Half Value Layer (HVL) and Tenth Value Layer (TVL) indices. A 

three parameter model used in diagnostic X-ray shielding is also fitted to the 

data allowing for the calculation of barrier thicknesses necessitated by any 

combination of distance, occupancy and facility workload to arrive at a design 

goal dose limit. The effect of patient attenuation, which is significant for lower 

energy photon emitters, is discussed using transmission data through water. 

Conclusions: While HVL and TVL data are the current cornerstone of 

brachytherapy facility shielding, the combination of an accurate representation 

of broad beam transmission data with an analytical expression to describe 

them, could greatly promote accuracy and simplicity. *Work done 

within the framework of the GEC-ESTRO BRAPHYQS group. 

121 oral 

THE RECONSTRUCTION OF BRACHYTHERAPY RING APPLICA- 

TORS DIRECTLY ON MR IMAGES 

D. Berger 1 , J. Dimopoulos 1 , R. Pötter 1 , C. Kirisits 1 

1 MEDICAL UNIVERSITY OF VIENNA, Radiotherapy, Vienna, Austria 

Purpose: The purpose of this study was to introduce direct reconstruction 

method for intracavitary tandem ring applicators in MRI based brachytherapy 

treatment planning and test the feasibility for clinical use. 

Materials: The Vienna ring applicator was systematically used in 10 clinical 

insertions. Reconstruction and dose calculation was performed independently 

on two treatment planning systems (PLATO v14.3 and OncentraGYN 

v0.9, both Nucletron). DVH parameters (per fraction, prescribed dose 7Gy) 

D90 for the target HR-CTV, D2cc for organs at risk (bladder, rectum and sigmoid) 

were analyzed and compared to the up to now in clinical practice used 

radiograph/MRI registration based method using PLATO EVAL. To achieve 

equivalent treatment plans for all reconstructions (source strength and dwell 

times/weights were taken from the clinical used reference plan. Reconstruction 

was performed with back projection using pre defined library plans and 

3 anchor points (registration points) defined at 1st source position of ring, 

tandem and the ring center. The first source position inside the ring is not 

visible on MRI. The orientation of the ring applicator can be identified by 

holes drilled into the ring as they become visible due to body fluids when 

the applicator is inside the patient. Exact coordinates of first ring source 

position relative to drilled ring holes and the outer shape were optically measured 

at dedicated transparent ring phantoms. Geometric information’s were 

plotted on transparency (for use at PLATO) and defined in a template configuration 

file (OncentraGYN). The 1st ring source position was digitized on 

para-transverse oriented MRI slices. When PLATO was used for reconstruction, 

the transparency was placed on the screen and rotated to fit with the 

visible ring holes, while in OncentraGYN the existing applicator geometry information 

(outer surface and source path) was directly used when positioning 

the visible parts of the applicator into the 3D MRI dataset. 

Results: Both methods can be used and reduce the time for treatment 

planning substantially. The built-in solution in OncentraGYN was superior 

to the manual fit of a transparency on the screen. DVH parameters 

evaluated at plans using reconstruction directly on MRI differ from 

the clinical used plans as follows (mean differences ): for OncentraGYN 

by 0.2±0.4Gy, -0.2±0.4Gy, 0.2±0.3Gy, 0.0±0.2Gy and for PLATO by 

0.1±0.9Gy, -0.1±0.5Gy, 0.2±0.2Gy, 0.1±0.2Gy for HR-CTV-D90, bladder- 

D2cc, rectum-D2cc and sigmoid-D2cc , respectively. 

Conclusions: The introduced direct reconstruction method on MRI when 

using the Vienna applicator is clinical feasible and is applicable on treatment 

planning systems when the exact geometry of the ring applicator is known 

and implemented. 

122 oral 

QUALITY ASSURANCE FOR PROSTATE BRACHYTHERAPY 

B. Al-Qaisieh 1 , D. Baltas 2 , T. P. Hellebust 3 , F. A. Siebert 4 , C. Kirisits 5 , J. 

Venselaar 6 

1 

ST JAMES’S INSTITUTE OF ONCOLOGY, Department of Medical Physics 


2 

STRAHLENKLINIK, Department of Medical Physics and Engineering, 

Offenbach, Germany 

3 

RIKSHOSPITAL-RADIUMHOSPITAL HEALTH TRUST, Department of Medical 

Physics, Oslo, Norway 

4 

UNIVERSITY HOSPITAL OF SCHLESWIG-HOLSTEIN, Clinic of Radiotherapy, 

Kiel, Germany 

5 

MEDICAL UNIVERSITY OF VIENNA, Department of Radiotherapy, Vienna, 

Austria 

6 

DR. B. VERBEETEN INSTITUUT, Department of Radiotherapy, Tilburg, 

Netherlands 

Purpose: To produce guidelines and recommendations to perform quality 

assurance (QA) tests for High Dose Rate (HDR) and Low Dose Rate (LDR) 

prostate Brachytherapy implants. 

Materials: A comprehensive checklist of QA procedures, to be carried out as 

standard practice for prostate Brachytherapy, was identified by the GEC ES- 

TRO BRAPHYQS Group. An extensive literature search in combination with 

experience provided by members of the ESTRO BRAPHYQS Group were 

used to propose methods to carry out relevant QA tests. 

Results: The QA checklist covers a wide range of areas such as procedure 

risk assessment, source calibrations, needle/catheter loading and commission, 

template/grid calibration, stepper unit, ultrasound machine check, 

clinical commissioning of planning System, treatment plan check, and post 

implant dosimetry. For each of these areas, an efficient and practical QA 

procedure was designed. 

Conclusions: A comprehensive QA system for prostate Brachytherapy is 

required to enhance and promote high quality medical practice. Such comprehensive 

systems ensure that patients receive doses that are as low as 

reasonably practical (ALARP). 

123 oral 

DOSE-VOLUME HISTOGRAM BASED INVERSE OPTIMIZATION 

FOR CERVIX CANCER BRACHYTHERAPY PLANNING: IMPLEMEN- 

TATION OF CLINICAL EXPERIENCE FROM MANUAL TREATMENT 

PLANNING 

P. Trnkova 1 , D. Baltas 2 , J. Dimopoulos 1 , R. Pötter 1 , C. Kirisits 1 

1 


Austria 

2 

KLINIKUM OFFENBACH GMBH, Department of Medical Physics and 

Engineering, Offenbach am Main, Germany 

Purpose: HIPO (Hybrid Inverse Planning Optimization) has been adapted as 

a new anatomy based inverse optimization tool for cervix cancer brachytherapy. 

Its objective is to create treatment plans with better coverage for target 

structures and lower dose to organs at risk. This study compares the dosimetric 

differences to manually optimized treatment plans. 

Materials: Ten tandem/ring (T/R) applicator and ten cases with additional 

needles (T/R+N) were included with plan for 7 Gy per fraction created with 

PLATO (release 14.3, Nucletron) within clinical routine. For all patients, standard 

loading patterns were consequently manually optimized to reach the 

best coverage of High Risk-CTV and to spare organs at risk. The second 

plan was retrospectively created with OncentraGYN (release 0.9.14, Nucletron). 

For all patients, anatomy based loading patterns were used for opti-


mization with HIPO using fixed reconstructed catheter positions. All inverse 

plans were based on dwell time gradient restriction, and different optimization 

constraints for T/R and needles to preserve the spatial high dose and dwell 

time distribution as accepted for manual plans. 

Results: For all T/R and 7 T/R+N patients, a better coverage of target (V100) 

was achieved with HIPO. The D90 was on average higher by 0.2 ± 0.6 Gy 

(mean difference ± SD). For 7 patients, D90 was lower but never >4% compared 

to manual, except one case where it still reached 140% of prescribed 

dose. The D2cc per fraction for bladder, rectum and sigmoid was on average 

lower by 0.2 ± 0.5 Gy, 0.4 ± 0.2 Gy, 0.2 ± 0.3 Gy respectively for T/R 

patients and 0.6 ± 0.7 Gy, 0.3 ± 0.5 Gy, 0.3 ± 0.3 Gy for T/R+N patients 

(a decrease from 4.5 to 4 Gy per fraction means a total dose reduction of 

5 Gy EQD2 dose for a 4 fraction schedule). The whole implant volume was 

lower in 17 cases for VPD, in 16 for V2xPD and in 17 for V4xPD when HIPO 

was applied. The amount of time needed for autoactivation of dwell positions, 

several optimization runs (each 50 ◦ C). 

Conclusions: The robot is MRI compatible and operates well inside a 1.5T 

magnetic field without causing image artefacts. Accurate needle tracking is 

feasible on MR images that can be acquired in seconds. Titanium needles, 

20 cm long, are safe to use in MR scanners up to 3T. MRI guided prostate 

brachytherapy seems feasible with this robot. 

125 oral 

S 41 

AN APPROACH TO CONVENTIONAL BRACHYTHERAPY TREAT- 

MENT PLANNING TO SIMULATE COMPLEX DOSE DISTRIBUTIONS 

M. Rivard 1 , C. Melhus 1 , J. Perez-Calatayud 2 , D. Granero 2 , F. Ballester 3 

1 

TUFTS MEDICAL CENTER, Department of Radiation Oncology, Boston, 

USA 

2 

HOSPITAL LA FE, Radiotherapy, Valencia, Spain 

3 

UNIVERSITY OF VALENCIA-IFIC, Atomic, Molecular, and Nuclear Physics, 

Valencia, Spain 

Purpose: Conventional brachytherapy treatment planning relies on entry 

of single-source dose distributions determined via measurements or Monte 

Carlo simulations in a large, homogenous liquid water medium. This approach 

relying on the superposition principle of individual seed dose distributions 

to replicate the total dose distribution works well for low dose rate 

prostate implants. However, there are many situations where this environment 

will differ from a clinical implant, and the resultant dose distribution 

obtained from the treatment planning system will be significantly inaccurate 

given common clinical requirements. These situations include plaque therapy 

where patient scatter conditions and patient geometry are not addressed 

using the current AAPM TG-43 brachytherapy dosimetry formalism. Specifically, 

methods have been established to integrate complex shielding and air 

gap behaviors into the calculated source distributions to improve treatment 

planning system accuracy for these treatments. 

Materials: High-resolution dose distributions from complex brachytherapy 

plaques determined using Monte Carlo methods were used as input data. 

These included COMS-based eye plaques using 125 I, 103 Pd, and 131 Cs; 4- 

8cm diameter AccuBoost peripheral breast brachytherapy applicators from 

Advanced Radiation Therapy; and the Leipzig and Valencia skin applicators 

from Nucletron Corp. Brachytherapy dosimetry parameters were derived by 

positioning the coordinate system axis origin along the cylindrical dose distribution 

axis of symmetry, and entered into a conventional treatment planning 

system (e.g., Pinnacle by Philips). Dose distributions were subsequently calculated 

and compared to the original Monte Carlo-derived dose distributions. 

Results: Complex brachytherapy dose distributions were accurately reproduced 

by the planning system, and generally yielded agreement within ~2% 

as compared to > 60% errors associated with conventional brachytherapy 

planning techniques. Differences with the input data using our technique were 

attributed to linear interpolation errors, and were largest near the field edge 

and near the tissue boundary (i.e, skin or sclera). Dosimetric agreement improved 

as the spatial resolution of the fitted dosimetry parameters improved, 

and was visually indistinguishable from the complex Monte Carlo input data. 

Conclusions: A new brachytherapy treatment planning technique was developed 

to simulate complex brachytherapy dose distributions in tissue using 

conventional treatment planning software. This approach produced 

more accurate estimates of patient dose distributions than the conventional 

brachytherapy dosimetry formalism. The approach and favorable results 

should be generalizable to other source/tissue types, geometries, and planning 

systems.


Molecular Targeting and Radiosensitization 

126 oral 

ENHANCEMENT OF RADIATION RESPONSE IN P53-DEFICIENT 

CANCER CELLS IN VIVO USING DIFFERENT SCHEDULES OF 

RADIATION AND AZD1152, AN AURORA B KINASE INHIBITOR 

Y. Tao 1 , C. Leteur 2 , V. Frascogna 2 , P. Zhang 2 , P. Opolon 3 , K. Mundt 4 , 

G. Kroemer 5 , J. Bourhis 1 , E. Deutsch 1 

1 INSTITUT GUSTAVE-ROUSSY, Radiotherapy, Villejuif, France 

2 INSTITUT GUSTAVE-ROUSSY, UPRES EA27-10, Villejuif, France 

3 INSTITUT GUSTAVE-ROUSSY, UMR 8121, Villejuif, France 

4 ASTRAZENECA, Macclesfield, Cheshire, United Kingdom 

5 INSTITUT GUSTAVE-ROUSSY, U848, Villejuif, France 

Purpose: Overexpression of Aurora kinases has been correlated with cancer 

susceptibility and poor prognosis in many human cancers. We have recently 

shown the ability of AZD1152, an Aurora kinase inhibitor with selectivity for 

Aurora B kinase, to enhance the effect of irradiation. This effect was also observed 

using siRNA, or by transfection with an inducible kinase-dead Aurora 

B in p53-deficient cancer cells (Oncogene, in press). The aim of the study 

reported here was to evaluate the effect the scheduling of AZD1152 administration 

on radiosensitivity and the effect AZD1152 on fractionated radiation. 

Materials: AZD1152 is a highly potent Aurora kinase inhibitor selective for 

Aurora B kinase. AZD1152 is a phosphate pro-drug that is converted in vivo 

to the active moiety AZD1152-HQPA. 60Coγ-ray was used for in vivo (nude 

mice) irradiation. 

Results: We have previously shown that 4-day administration of AZD1152 

35 mg/kg/day increased radiation cell killing in the p53-/- HCT116 cell line in 

vivo. In the current study, we administered a single dose of AZD1152 160 

mg/kg in vivo following delivery of one 8 Gy fraction of radiation. This single 

dose of AZD1152 did have an effect on tumor growth inhibition but the 

effect was not increased when the compound was combined with radiation. 

We next compared three different schedules of radiation and AZD1152 (4day 

dosing of 35 mg/kg/day): neo-adjuvant schedule, AZD1152 on days 1 

to 4 then one fraction of 8 Gy radiation on day 5; adjuvant schedule, one 

fraction of 8 Gy radiation on day 1 and then AZD1152 on days 2-5; concomitant 

schedule, AZD1152 on days 1-4 combined with one fraction of 8 Gy 

radiation on day 1. Significantly greater tumor growth delays were observed 

when AZD1152 was combined with radiation compared with administration 

of radiation or AZD1152 alone in all three schedules. We have shown that 

AZD1152 enhanced the in vivo cell killing effect not only when combined with 

single dose (8 Gy) irradiation, but also when combined with fractionated radiation 

(2.5 Gy for 4 days concomitantly delivered with 4 days of AZD1152 35 

mg/kg/day). Finally, we show that AZD1152 can lead to mitotic catastrophe in 

cancer cells in vitro and in vivo by inducing micronuclei and multinucleation. 

Conclusions: This study demonstrates that different schedules of administration 

of AZD1152 and radiation can enhance radiation-induced cell death 

in p53-deficient cancer cells in vivo. These preclinical data support further 

clinical exploration of scheduling of chemo-radiotherapy and fractionated radiotherapy 

as frequently used in clinical practice. 

127 oral 

A NOVEL THERAPEUTIC MODEL THAT COMBINES ADENOVIRAL- 

MEDIATED NIS GENE THERAPY, EXTERNAL BEAM RADIOTHER- 

APY (EBRT) AND RADIOSENSITISING AGENTS (DNA-REPAIR 

INHIBITORS) IN NON-THYROID CANCER 

M. Hingorani 1 , C. White 1 , K. Copeland 1 , S. Zaidi 1 , A. Merron 2 , I. 

Peerlinck 2 , G. Vassaux 2 , G. Smith 3 , A. Slade 3 , K. Harrington 1 

1 

INSTITUTE OF CANCER RESEARCH, Targeted Therapy Laboratory, London, 


2 

JOHN VANE SCIENCE CENTRE, Center for Molecular Oncology, London, 


3 

KUDOS PHARMACEUTICALS, Cambridge, United Kingdom 

Purpose: Sodium Iodide Symporter (NIS) is a transmembrane protein that 

mediates active iodide transport in the thyroid gland. NIS gene therapy (NGT) 

enables treatment of non-thyroidal tumour cells with radioisotope therapy. In 

combination with EBRT, this may achieve tumour-specific escalation of radiation 

dose. We propose a therapeutic model of adenoviral-mediated NGT 

combined with EBRT and radiosensitising agents to treat non-thyroid cancer. 

Materials: Replication-deficient adenoviral vectors expressing NIS (CMV or 

tumour-specific telomerase (hTR) promoter), GFP (CMV), or luciferase (RSV 

promoter) were employed to transduce tumour cell lines (HCT116 (colorectal), 

SIHN-5B (Head & Neck), H1299 (lung)). NIS, GFP, and luciferase expression 

was quantitated using iodide-uptake, FACS, and bioluminescent imaging, 

respectively. Effect of EBRT (0, 4, and 8 Gy) on adenoviral-mediated 

gene expression and its modulation in the presence of DNA repair inhibition 

(DNA-PK inhibitor (KU-0057788)) was assessed. Effect of adenoviralmediated 

NIS (131I) cytotoxicity was evaluated in vitro using clonogenic assays. 

In vivo therapeutic effect of NIS-mediated radioiodide therapy, combined 

with EBRT and DNA-repair inhibition (DNA-PK inhibitor (KU-0060648)), 

was evaluated in nude mice bearing HCT116 xenografts. 

Results: EBRT induced a dose-dependent increase (upto 4-fold) in the level 

of adenoviral-mediated gene expression in vitro and in vivo. This was maintained 

at later time-points (5 days) after infection. Interestingly, the effect was 

further enhanced (upto 2-fold) by DNA repair inhibition, indicating that this 

was mediated by radiation-induced DNA damage. Furthermore, adenoviralmediated 

NIS (131I) cytotoxicity was enhanced after EBRT in HCT116 and 

SIHN-5B cell lines. Combining EBRT (8 Gy) with NIS-mediated 131I (1mCi) 

therapy in vivo was associated with a significantly greater reduction in tumour 

volume compared to that observed with either modality alone. At 5 weeks 

post-treatment, a 67% reduction in average tumour volume was observed 

in the combination arm, that contrasted with an increase (30%) in the volume 

of tumours in mice treated with RT or NIS-mediated 131I therapy alone. 

The maximal effect was observed when EBRT and NGT were combined with 

DNA-PK inhibitor (KU-0060648 (25mg/kg)) with complete regression of 90% 

tumours within 4 weeks (Figure 1). 

Conclusions: Adenoviral-mediated NGT, combined with EBRT and DNA repair 

inhibition is an attractive proposition for the treatment of non-thyroid cancer. 

Targeted NIS delivery should lead to tumour-specific cytotoxicity with 

sparing of normal tissues, combined with an improvement in therapeutic index. 

128 oral 

HETEROGENEITY OF THE EFFECT OF COMBINED FRACTION- 

ATED RADIOTHERAPY AND EGFR/HER2 TYROSINE KINASE 

INHIBITION 

K. Gurtner 1 , C. Schütze 1 , F. Solca 2 , M. Baumann 1 , M. Krause 1 

1 MEDICAL FACULTY AND UNIVERSITY HOSPITAL CARL GUSTAV CARUS, 

TECHNISCHE UNIVERSITÄ, Department of Radiation Oncology, OncoRay – 

Centre for Radiation Research in Oncology, Dresden, Germany 

2 BOEHRINGER INGELHEIM AUSTRIA, Vienna, Austria 

Purpose: Previous results confirmed an enhanced anti-proliferative effect of 

the EGFR/HER2 tyrosine kinase (TK) inhibitor BIBW 2992 (TOVOK R○ ) alone 

and after single dose irradiation of FaDu human squamous cell carcinoma 

(SCC) xenografts in vivo. The aim of the present study was to investigate the 

efficacy of a combined fractionated radiotherapy and administration of BIBW 

2992 using 5 different tumour models. 

Materials: Tumour growth delay defined as the difference in time to 2fold 

(GDV2) or 5fold starting tumour volume (GDV5) for treated and control groups 

was determined in 5 tumour models (A7 glioma and the SCC models FaDu, 

UT-SCC-14, A431, UT-SCC-15). To assess single agent activity of BIBW 

2992, tumor bearing NMRI (nu/nu) mice were fed daily with either BIBW 2992 

(20 mg/kg body weight) or carrier up to a final tumour diameter of 15 mm. 

The same treatment was applied to tumour bearing mice concomitantly with 

fractionated radiotherapy (15f/15d, total dose 30Gy, ambient) to assess the 

effect of the chemoradiation combination.


Results: In all tumour models, BIBW 2992 alone leads to a significant delay 

in tumour growth. However, considerable heterogeneity between the models 

exists. While only a slight delay in tumour growth could be observed in A7 

(enhancement ratio of 1.1 and 1.3 for GDV2 and GDV5), a pronounced tumour 

growth delay was seen in FaDu with an enhancement ratio of 12.8 for 

GDV2. In all other tumour models, during treatment time (56-60 days) total 

regressions of the tumours and no recurrences were seen. 

Conclusions: It has been shown that as a single agent administration of 

BIBW 2992 leads to a significant delay in tumour growth in all tumour models. 

However, the extent of this effect varies between the different tumour models. 

The significant effect of the drug alone translates into an improvement of the 

radiation effect after simultaneous treatment in 4/5 tumour models. Whether 

or not the tumour growth delay is consistent with an improvement of local 

tumour control and with differences in downstream signal transduction is currently 

being investigated in our laboratory. 

129 oral 

DORANIDAZOLE AS A RADIOSENSITIZER: COMPARISON WITH 

MISONIDAZOLE AND NIMORAZOLE 

M. R. Horsman 1 , R. Murata 1 , M. Tsujitani 2 , J. Overgaard 1 

1 

AARHUS UNIVERSITY HOSPITAL, Experimental Clinical Oncology, Aarhus 

C, Denmark 

2 

POLA PHARMA INC, Department of Pharmaceutical Planning, Yokohama, 

Japan 

Purpose: This study was designed to assess the potential of the nitroaromatic 

radiosensitizer doranidazole to preferentially enhance radiationinduced 

local control in a murine tumour and to compare that affect to data 

obtained with the classical nitroaromatic radiosensitizers that have shown efficacy 

in clinical trials, namely misonidazole and nimorazole. 

Materials: A C3H mammary carcinoma grown in the right rear foot of female 

CDF1 mice was used and treated when at 200 cubic mm in size. Doranidazole 

was dissolved in saline and injected intravenously. Radiation (240 kV 

x-rays) was locally administered to the tumours or normal feet of restrained 

non-anaesthetised animals. Response endpoints were local tumour control 

at 90 days and moist desquamation in foot skin 11-23 days after irradiation. 

Following logit analysis of the radiation dose response curves the TCD50 (tumour) 

or MDD50 (skin) doses (radiation doses producing a response in 50% 

of treated mice) were estimated and a sensitizer enhancement ratio (SER; 

ratio of the TCD50 or MDD50 for radiation alone and radiation with drug) calculated. 

Statistical analysis was performed using a Chi-squared test (p


Physics Treatment technologies 

132 oral 

CONSTRUCTION OF A HYBRID 1.5 T MRI ACCELERATOR FOR 

REAL-TIME SOFT-TISSUE BASED IMAGE GUIDANCE: STATUS 

REPORT 

B. Raaymakers 1 , J. Lagendijk 1 , A. Raaijmakers 1 , E. Kerkhof 1 , R. van der 

Put 1 , I. Van Dijk 1 , J. Kok 1 , M. van Vulpen 2 , J. Overweg 3 , K. Brown 4 

1 UMC UTRECHT, Radiotherapy, Utrecht, Netherlands 

2 UMC UTRECHT, Radiation Oncology, Utrecht, Netherlands 

3 PHILIPS RESEARCH, MRI, Hamburg, Germany 

4 ELEKTA UK LIMITED, Crawley, West Sussex, United Kingdom 

Purpose: Imaging is becoming increasingly important for the entire cycle of 

radiotherapy: treatment planning, delivery, response assessment and followup. 

All steps can gain from improved soft-tissue contrast for visualisation of 

the tumour and the organs at risk. MRI is an appropriate modality for offering 

exactly that. 

Materials: The Department of Radiotherapy, UMC Utrecht, The Netherlands, 

in collaboration with Elekta, Crawley, UK, Philips Medical Systems, Best, The 

Netherlands and Philips Research, Hamburg, Germany, is constructing a hybrid 

1.5T MRI radiotherapy system. This system can be used for real-time, 

soft-tissue based image guidance. This paves the way for high resolution 

dose painting for GTV boosting/ablation. Also PTV margins can be minimised 

to spare normal tissues.Preceeding research showed the technical feasibility 

of such a hybrid system. The design is a 6MV accelerator positioned in a 

ring around the MRI in the mid-transversal plane, this is schematically shown 

in the figure below. The magnet design is adjusted in order to minimise the 

magnetic interference and to minimise the absorption of the beam. 

Results: The prototype is planned for autumn 2008. The aim is to demonstrate 

MRI guided irradiation with sub- mm precision. The prototype will initially 

be static: the accelerator will be in a fixed lateral position. The treatment 

room preparation will be discussed including: creation of entrance route in 

bunker, faraday cage and passive magnetic room-shielding to minimise magnetic 

interference with neighbouring clinical accelerators. 

Conclusions: The current Geant4 Monte Carlo simulations on the accelerator 

output and radiation dosimetry will be verified in the prototype. Geant4 

simulations were also used to find suitable IMRT solutions in the presence 

of a 1.5T field, these will be evaluated experimentally. System related issues 

addressed will be the radiofrequency interference between the MRI and 

the accelerator, the geometric correction of images dedicated for this system 

and the geometrical coupling of the MRI and accelerator coordinate system. 

The hardware for acquiring real-time MRI data during irradiation, i.e. the MRI 

accelerator is the first requirement for MRI guidance. Additional steps are automatic 

target definition, decision making and plan adaptation. Our progress 

on automatic target definition wil be discussed as well as the quantification of 

the clinical benefit of MRI guidance. 

133 oral 

DEVELOPMENT OF 7 T MRI FOR RADIOTHERAPY TUMOUR 

CHARACTERIZATION. 

J. Lagendijk 1 , B. Van den Bergen 1 , A. Van Lier 1 , A. Raaijmakers 1 , D. 

Klomp 2 , P. Luijten 2 , C. van den Berg 1 

1 

UNIVERSITY MEDICAL CENTRE UTRECHT, Radiotherapy, Utrecht, 

Netherlands 

2 

UNIVERSITY MEDICAL CENTRE UTRECHT, Radiology, Utrecht, Netherlands 

Purpose: High field MRI has high promises for oncologic purposes. The 

higher magnetic field augments the signal of various functional imaging techniques. 

These include the higher spectral resolution for spectroscopy, the 

increased blood oxygenation contrast for BOLD, higher contrast of Susceptibility 

Weighted Imaging and the higher sensitivity to other elements than 

hydrogen such as 19 Fluor. These high field functional MR techniques open 

up new possibilities for radiotherapy to characterize the tumour with respect to 

radiosensitivity or follow changes in biochemical tumour environment during 

therapy. 

Materials: Recently, a 7 Tesla MR scanner was installed in Utrecht with oncology 

as one of the application spearheads. To make this high field MR scanner 

suitable for whole body oncologic imaging some technical challenges with 

respect to the radiofrequency (RF) field, used to excite the hydrogen nuclei, 

have to be overcome. The RF challenges for high field MRI originate from 

the inevitable increase of the frequency of the RF field with increasing field 

strengths. The high frequency, with its related smaller wavelength, leads to 

anatomy dependent interference patterns in the body. The final result is a 

highly non-uniform RF excitation (B1 + ) field and significant higher RF heating 

(SAR) at some areas due to local amplification of the electric field. In this 

study we investigated a method to solve these problems and enable 7 Tesla 

MR prostate imaging. Using electromagnetic simulations we have simulated 

the RF fields inside the patient and investigated whether by controlling the 

phase and amplitude of each RF transmit elements seperately, the B1 + field 

around in the prostate can be optimized while simultaneously reducing SAR 

levels to safe limits. 

Results: We have found that by individual control of the RF transmit elements, 

the B1 + field inside the prostate can be considerably improved with 

respect to conventional excitation. Although the optimized excitation outperforms 

the conventional excitation on both the B1 + and SAR aspect, it is possible 

to prioritize B1 + homogeneity or SAR. 

Conclusions: The RF field challenges of 7T prostate imaging can be overcome 

using a multi-transmit channel concept. Based on simulations, we expect 

that the B1 + excitation field in the prostate can optimized sufficiently to 

allow most functional sequences and stay with safe SAR levels. 

134 oral 

NORMAL TISSUE COMPLICATION PROBABILITIES (NTCP) IN 

STEREOTACTIC BODY RADIATION THERAPY (SBRT) FOR LUNG- 

CANCER; A MODELLING STUDY ON CLINICAL DATA 

B. Wennberg 1 , P. Baumann 2 , I. Lax 1 

1 

KAROLINSKA UNIVERSITY HOSPITAL AND INSTITUTE, Medical Physics, 


2 

KAROLINSKA UNIVERSITY HOSPITAL AND INSTITUTE, Oncology, Stock- 

holm, Sweden 

Purpose: In SBRT of peripheral lung tumors the incidence of clinical radiation 

pneumonitis (RP, grade 2 or more) is low (2-10%). This seems to be almost


irrespectively of prescribed dose as long as the tumor is relatively small. This 

is contradictory to clinical findings from conventional RT. The hypothesis in 

this work was that existing biological models does not fully describe SBRT. 

Materials: Seventeen patients suffering from inoperable non-small cell lung 

cancer, T1T2 N0 M0 were studied. The patients were treated by SBRT at 

Karolinska Universitetssjukhuset, Stockholm, with 15 Gy x 3 prescribed to 

the 65% isodose at the periphery of the PTV, resulting in a central dose of 

22 Gy x 3. The mean GTV dose and volume were 66 Gy (physical dose) 

respectively 7 cc and the mean lung-GTV dose volume were 6.9 Gy (physical 

dose) respectively 2071 cc. All patients were calculated with a PB algorithm 

on TMS-Helax (v6.1b) by Nucletron. Ten percent had RP, grade 2 or more 

(NCI-CTC). DVH for the lung tissue was corrected with the multitarget model 

instead of the LQ-model. Thus the high dose region of the DVH’s was corrected 

assuming an exponential survival curve, after the shoulder, instead of 

the continous bending curve as predicted by the LQ model. NTCP values 

for lung complication (RP grade 2 or more) were calculated with the Lyman- 

Kuther-Burman (LKB) model. Published parameter values from conventional 

radiotherapy, assuming a parallel architecture of functional subunits, as well 

as parameter values assuming a more serial architecture was used 

Results: NTCP values calculated with lung-DVH corrected with the multitarget 

model and assuming a more serial architecture could improve the fit to 

clinical data. This may in part be explained by the anatomy of the lungs. If 

parts of the fine bronchii are damaged by radiation the part of the lung beyond 

that may not function properly, eventually leading to clinical symptoms. 

Conclusions: In localized treatment of lung tissue up to very high doses, 

such as in SBRT, the response seems to correspond more a like serial architecture 

of the functional subunits. 

135 oral 

DETECTOR-BASED DOSIMETRY AND QA OF A HELICAL TO- 

MOTHERAPY UNIT 

K. Tournel 1 , I. Van De Vondel 1 , D. Verellen 1 , S. Lelie 1 , M. Duchateau 1 , 

N. Linthout 1 , T. Reynders 1 , T. Gevaert 1 , G. Storme 1 

1 ONCOLOGY CENTER UZ BRUSSEL, Radiotherapy, Brussels, Belgium 

Purpose: In Tomotherapy dose is highly dependant on the output and shape 

of the beam (’cone’). Variations in these can have huge influences on IMRTtreatments 

and daily monitoring is required, but are time consuming using 

conventional methods. This study presents an in-house developed tool (’TomoCheck’) 

that is completely automatic and independent of classical dosimetric 

tools and will reduce QA time significantly. 

Materials: A software package was developed to run independently on the 

system and retrieve the integrated CT-detector and dosechamber data directly 

without any need for pre-processing. The system will compare daily 

cone profiles and output of the three system dose chambers to a fixed reference 

and will analyze these signals to calculate target and magnetron condition. 

All measurements are logged, allowing for system monitoring in time. 

The ability to monitor daily output changes was tested by using static fields 

and ionization chamber(IC) measurements. To validate the link between output, 

cone and daily patient QA measurements a dedicated IMRT-plan containing 

disjunct targets on and off the machine axis was used and a linear 

regression model was built to check for consistency between the tomocheck 

variables (mean variations of output and cone) and the IMRT measurements. 

This would allow thresholds for action levels to be set on the TomoCheck 

variables. 

Results: Results show that the in-house tool can be used to monitor output 

and cone shape on tomotherapy in a fast and reliable way. Furthermore, 

the system has the ability of separating effects of output and cone in one 

single measurement. The static beam measurements using IC show a correspondence 

within 2% after elimination of the cone effect. Using a 6D-linear 

regression the software can predict IMRT-ionization chamber measurements 

within 0.7%, and a 2% threshold on cone and output values can be used in 

daily routine. Early results show that the model’s instabilities model could 

predict problems such as target or magnetron failure prematurely. 

Conclusions: The in-house developed software tool based on direct detector 

and dose-chamber monitoring can be used to monitor output- and conevariation 

in 1 procedure. By using a regression the tool can also replace 

IMRT-QA measurements. Combined, this allows for daily QA-time reduction 

from 50 to 5 minutes. 

136 oral 

S 45 

DEVELOPMENT OF A NATIONAL PROTOCOL FOR EVALUATING 

THE PERFORMANCE OF X-RAY VOLUMETRIC IGRT SYSTEMS 

R. Lindsay 1 , J. Sykes 1 , D. Thwaites 1 

1 LEEDS TEACHING HOSPITALS TRUST, Department of Medical Physics and 

Engineering, Leeds, United Kingdom 

Purpose: The Centre for Evidence Based Purchasing (UK government) has 

a remit to evaluate medical equipment to inform local and national purchasing 

decisions. We have developed a protocol to comparatively benchmark the 

technical performance of three X-ray Volumetric IGRT systems. 

Materials: A protocol for evaluation was developed on the Elekta Synergy 

system. A full set of tests were then repeated at a Varian and TomoTherapy 

test centre. A sub-set of tests will shortly be repeated at four Elekta and 

three Varian test sites to determine consistency of performance across multiple 

installations and statistical significance of any manufacturer dependent 

differences. 

Results: The evaluation protocol was split into three categories: image guidance 

geometric accuracy, imaging dose and, image quality. Image guidance 

accuracy had two components: an alignment check of imaging and treatment 

delivery systems using the QUASAR Penta-Guide phantom and a full 

circle Image-Correct-Verify test based on soft tissue using the Virtually Human 

Male Pelvis phantom. The imaging dose protocol employed a Farmer 

chamber traceable to national standards in either two CTDI phantoms for full 

tests or one CTDI phantom for a subset of tests at the evaluation centers. 

Image quality parameters such as resolution, uniformity, contrast and noise 

were measured in the CATPhan-600 using the measurements of dose to relate 

contrast to noise across all systems. 

Conclusions: The protocol developed sets standards in evaluating these 

types of system. The results from the evaluation in conjunction with a complete 

functional specification of each system will be used to compile a buyer’s 

guide. 

137 oral 

THE IMPACT ON IMAGE REGISTRATION QUALITY WHEN THE 

NUMBER OF PROJECTIONS IN A 3D CONE-BEAM CT RECON- 

STRUCTION IS REDUCED 

J. Westberg 1 , H. Jensen 1 , A. Bertelsen 1 , C. Brink 1 

1 LABORATORY OF RADIATION PHYSICS, Odense University Hospital, 

DK-5000 Odense, Denmark


Purpose: The acquisition time and dose delivery of a 3D cone-beam CT scan 

(CBCT) depends on the number of projections. A full standard 360 ◦ CBCT 

used for patient position verification on the accelerator takes approximately 

120 seconds to acquire with the standard number of projections (typically 

630). A fewer number of projections can reduce the total scan time and dose 

to the patient. The fewer projections will evidently have an impact on the image 

quality of the reconstruction. The purpose of this project is to determine 

how much we can reduce the number of projections, and still maintain an image 

registration of the therapy planning CT and the CBCT comparable to the 

one obtained by a full standard scan. 

Materials: The X-ray Volume Imaging (XVI) software is used for reconstruction 

of the CBCT and the image registration. XVI provides a feature to select 

which projections to include in the 3D CBCT reconstruction. This boolean flag 

can be turned either on or off automatically for each projection by accessing 

the XVI database directly. The number of projections was reduced by selecting 

the first projection in the rotation and then every second, third, fourth, and 

tenth for each trial, reducing the number to 50%, 33%, 25%, and 10% respectively. 

Our preliminary data was made with the Alderson phantom scanned at 

an Elekta Synergy accelerator with a XVI CBCT system, and reconstructed 

using the M20 High Resolution preset. Image registration was carried out 

for both of the two algorithms available in XVI software, one based on bone 

density values and the other on all density values (named grey values). Both 

registrations were compared with the results from the full standard scan. 

Results: The reduced number of projections does not have a significant impact 

on the image registration of the Alderson phantom. Surprisingly the 

registrations gave almost the same results when using only 10% of the projections. 

The length of the absolute couch shift was less than 1.2 mm for 

the bony registration method and less than 0.2 mm for grey value. These 

differences are relative small compared to an overall acceptance limit on the 

patient position of 5 mm as used in many institutions. 

Conclusions: Using only 10% of the projections in the XVI software results 

in an image registration similar to the one based on the full standard scan. 

Visually there is a reduction of the image quality, however 3D XVI CBCT is not 

used as a diagnostics tool and thus visual quality is not an issue. The reduction 

in number of projections will reduce the acquisition time and dose given 

to the patient. Our ongoing clinical study will show whether this reduction 

holds for clinical patients as well. 

Rotational therapy 

138 oral 

INFLUENCE OF HARDWARE CONSTRAINTS ON THE PLAN QUAL- 

ITY IN ROTATION THERAPY 

S. Ulrich 1 , S. Nill 1 , U. Oelfke 1 

1 GERMAN CANCER RESEARCH CENTER, Medical Physics, Heidelberg, 

Germany 

Purpose: Rotation therapy with variable dose rate (called VMAT, rapidarc 

therapy or arc-modulated cone beam therapy (AMCBT)) currently becomes 

avaiable at first clinical sites. This fast treatment technique utilizes a single 

rotation of the gantry with variable aperture shapes and weights to deliver the 

complete dose. In this work we examined the impact of hardware constraints 

on the quality of achievable clinical dose distributions. 

Materials: Our AMCBT treatment planning approach starts from anatomy 

based initial aperture shapes and optimizes the beam weights with a fast gradient 

algorithm, while the aperture shapes are determined with a global tabu 

search algorithm. To account for limitations that are caused by the hardware 

the following constraints were included into the optimization: a minimum and 

maximum beam weight (depending on the dose rate of the linac), a maximum 

change of consecutive beam weights (depending on the achievable variation 

of the dose rate per second) and a maximum change of consecutive aperture 

shapes (depending on the speed of the MLC leaves). All these limits depend 

on the gantry rotation speed, which is calculated based on the total number 

of MUs to be delivered and is assumed to be constant for one treatment. For 

the optimization we assumed a gantry speed between 50-360 ◦ /min, a dose 

rate between 30-300 MU/min that can be varied by 15 MU/min per second 

and a maximum MLC leave speed of 3 cm/s. 

Results: For four clinical cases (prostate, head, pancreas) we optimized 

treatment plans for AMCBT with and without constraints. The gantry rotation 

speed was between 133 ◦ /min and 316 ◦ /min for the different cases, resulting 

in treatment times between 2.7 minutes and 1.2 minutes. The treatment 

plan generated with an unconstrained optimization was defined as the optimal 

dose distribution for the respective case. The consideration of MLC related 

restrictions into the optimization did not lead to any differences in the dose 

distribution. However, the dose rate constraints resulted in an increase of 

the objective function and observable differences in the dose distribution. As 

an example the impact of the limitations on the number of MUs per beam is 

shown in figure1. 

Conclusions: For some cases the range of the dose rate stated above is 

not sufficient to completely exploit the potential advantages of dynamically 

modulated rotation therapy. Limitations imposed by the MLC leave speed did 

not lead to a degradation of the plan quality. 

139 oral 

RAPIDARC TREATMENT FOR HEAD AND NECK TUMORS, A 

PLANNING STUDY WITH DOSIMETRIC VALIDATION 

W. Verbakel 1 , S. Senan 1 , D. Hoffmans 2 , B. Slotman 1 , J. Cuijpers 1 

1 VUMC, Radiation Oncology, Amsterdam, Netherlands 

2 VUMC, FMT, Amsterdam, Netherlands 

Purpose: A novel approach for planning and delivery with an aperture base 

method of intensity modulated single arc therapy is now available with RapidArc 

(Varian Medical Systems). This allows for delivery of typical head and 

neck treatment plans with a single 360 ◦ arc in less than 2 minutes per fraction, 

while achieving IMRT-like dose distributions. As such, RapidArc (RA) 

can be of large benefit to both patients and departments. We report the first 

planning comparison between RA and IMRT for 9 cases of head and neck 

tumors, with dosimetric validations of four of the plans. 

Materials: RapidArc plans using pre-clinical versions (8.2.14 and 8.2.16) 

were generated for nine head and neck patients with advanced disease and 

compared with the clinical sliding-window 7-field IMRT plans (Eclipse 8.1.14). 

All plans had a simultaneous integrated boost (SIB) of 2 Gy per fraction. 

Parotid glands, spinal cord, brainstem, oral cavity and trachea were delineated 

as organs at risk (OAR). Dose to OARs, PTV coverage and conformity 

index (CI) were compared between RA and IMRT. Six of the RA plans were 

re-optimized by means of a "base dose plan", resulting in a final plan consisting 

of 2 arcs. This was compared to a single arc RA and IMRT plans. 

Four of the single arc plans were delivered with a Varian Linac and measured 

in a solid water phantom in 5 coronal planes, 2 cm separated, using 

double Gafchromic R○EBT films. Measured and calculated dose distributions 

were compared using 2D gamma evaluation with limits of 2 mm and 3.5% (of 

typical PTV dose in phantom). 

Results: RapidArc treatment planning, a largely automated procedure and 

comparable to IMRT, could be performed in approximately 1 hour per patient. 

Average number of monitor units for single arc plans was 459 versus 1104 

for IMRT. Average dose to OAR was similar for RA and IMRT. CI was slightly 

worse for the single arc RA plan (boost: 1.14 b 0.09 vs. 1.22 b 0.04), and dose 

in PTV was less homogeneous for RA. All plans based on two arcs resulted in 

excellent PTV homogeneity, which was better than IMRT. The average relative 

volume of the elective PTV receiving more than 107% of its prescribed dose 

was 6.9, 14.3 and 3.4%, respectively, for the IMRT, single RA and double 

RA plans. Number of MU increased minimally for double RA and calculated 

treatment time increased to 3 minutes. Film measurements agreed well with 

calculations, average gamma was 0.33 and on average 2.4% of film surface 

had a gamma >1. The figure shows a typical gamma map (mean=0.33) of 

a film measurement. For the plan with largest deviations, maximum 7.6% 

of film surface had a gamma >1. All film measurements showed stronger 

modulation of dose than was calculated. 

Conclusions: Film measurements show that RA accurately delivers the 

planned dose distributions. RA using two arcs led to major improvement of 

the PTV dose homogeneity. Given the similar sparing of OARs and a major 

decrease in treatment duration, RapidArc delivery for head and neck tumors 

appears superior to ’conventional’ IMRT.Research was done in collaboration 

with Varian Medical Systems


140 oral 

COMPARISON AT PLANNING LEVEL BETWEEN VARIAN RAPIDARC 

AND HELICAL TOMOTHERAPY FOR SMALL BENIGN BRAIN 

TUMORS. 

A. Clivio 1 , A. Fogliata 1 , G. Nicolini 1 , E. Vanetti 1 , S. Yartsev 2 , L. Cozzi 1 


2 LONDON REGIONAL CANCER CENTRE, Medical Physics, London, Canada 

Purpose: The potential benefits and limitations of the new volumetric aperture 

based intensity modulated arc therapy (RapidArc, RA) from Varian and 

of the Helical Tomotherapy (HT) were investigated on a cohort of ’benign’ 

brain tumours. RapidArc consists of a planning and delivery method based 

on a single arc where multileaf collimator, dose rate and gantry speed are 

optimised simultaneously to achieve the needed degree of modulation. RapidArc 

is based on direct aperture field optimisation. The entire process aims 

to reduce delivery time and to minimise monitor units per Gy needed. 

Materials: Plans for five acoustic neurinomas (prescription: 50 Gy, 2Gy per 

fraction), five meningiomas (60 Gy, 2Gy/fr) and two pituitary adenomas (54 

Gy, 2Gy/fr) were computed to generate dose distributions using a common 

CT dataset to delineate planning target volume and organs at risk. For the 

present study, RapidArc was investigated for a 6MV beam from a Varian linear 

accelerator equipped with the new High Definition MLC (with 2.5 mm leaf 

width at isocentre in the central 8 cm of the field and 5 mm in the outer 2x7 

cm field parts). 

Results: HT and RA resulted equivalent in terms of target coverage. V95% 

was 100% for both techniques while D99% was 97.0+-1.2 and 96.8+-1.7 while 

Conformity Index was 2.5+-0.7 and 2.3+-0.9 for RA and HT. Sistematic differences 

where on the contrary substantiated for organs at risk. In particular 

maximum significant dose (D1%) was: 34.0+-13.4 vs 38.2+-12.4 (RA vs HT) 

on brain stem 32.9+-24.3 vs 36.6+-23.3 on optic chiasm, 7.5+-6.7 vs 11.7+- 

9.9 for ipsilateral optic nerve and 4.0+-2.6 vs 5.9+-2.9 for ipsilateral eye. For 

healthy tissue (brain minus target) the Integral dose was 8.7+-3.4 vs 10.4+- 

4.2 (RA vs HT) while V10Gy was 9.2+-6.1 Gy and 12.1+-8.2 Gy respectively. 

MU per Gy for RA were 26.0+-25 while for HT were roughly a factor 10 higher 

but due to the different delivery methods it is difficult to perform a direct comparison. 

Conclusions: Both techniques provided good target coverage and primarily 

differed in organs at risk and healthy tissue with RA resulting in general better 

sparing of involved serial organs as well as a reduction of 2-3 Gy in the 

bath at medium dose levels, with potential impacts on patients with long life 

expectancy. 

141 oral 

DMLC MOTION TRACKING OF MOVING TARGETS FOR INTENSITY 

MODULATED ARC THERAPY TREATMENT 

J. Zimmerman 1 , S. Korreman 1 , G. Persson 1 , H. Cattell 2 , M. Svatos 2 , A. 

Sawant 3 , R. Venkat 3 , D. Carlson 3 , P. Keall 3 

1 



2 

VARIAN MEDICAL SYSTEMS, Palo Alto CA, USA 

3 

STANFORD UNIVERSITY, Stanford, USA 

S 47 

Purpose: Intensity modulated arc therapy offers great advantages with the 

capability of delivering a fast and highly conformal treatment. However, moving 

targets represent a major challenge. Tracking of a moving target makes 

it possible to let the beam follow the motion, shaped by a dynamic MLC 

(DMLC). The purpose of this work was to evaluate the dose delivered to moving 

targets using the RapidArc (Varian) technology with and without a DMLC 

tracking algorithm. 

Materials: A Varian Clinac 21iX was equipped with RapidArc and a 3D DMLC 

tracking application. A motion platform was placed on the couch, SI amplitude 

1 cm and motion cycle 5-6 seconds, with the detectors on top. A PTW 

seven29 and a Scandidos Delta4 was used, the latter capable of measuring 

dose stepwise at 177 control points for each beam. Two RapidArc plans 

were delivered, a lung tumour plan (arc angles 179 ◦ -181 ◦ , target dose 2.0 

Gy) and a prostate plan (arc angles 200 ◦ -160 ◦ , target dose 3.3 Gy). Motion 

was tracked using a Real-time Position Management (RPM) system (Varian). 

For each detector and plan respectively, reference measurements were 

performed at state (0) "no motion, no tracking". Comparing measurements 

were made at states: (1) "motion, no tracking"; (2) "motion, tracking"; (3) "no 

motion, tracking"; (4) "no motion, tracking, no input from the RPM system". 

Gamma evaluation analysis was made with the criteria 3% dose difference, 

3mm Distance to Agreement. 

Results: Figure 1 shows the fractions of measurement points passing the 

gamma test of states (1) and (2) for both plans and both detectors respectively. 

There was a significant improvement of the gamma tests between 

measurements without and with tracking (Lung plan: 52% to 68% for PTW 

and 87% to 97% Delta4; Prostate plan: 49% to 66% PTW and 81% to 88% 

Delta4). The different levels between the instruments may be explained by 

their difference in detector size and detector plane orientation. The Delta4 

stepwise dose information clearly showed for state (1) an under- respective 

overdosage, periodically shifting from one end to the other along the fields’ 

SI-direction for both plans, as expected. This phenomenon was completely 

gone for state (2) measurements. State (3) and (4) together with repeated 

measurements of all states (PTW) showed a high level of noise coming from 

the RPM system, which deteriorated the improvement in the use of the tracking 

algorithm. 

Conclusions: It has been shown that the present 3D DMLC tracking algorithm 

is capable of improving the dose distribution delivered by RapidArc 

plans to a moving target. The test also showed the great importance of minimizing 

the noise in the tracking system for reaching the full benefit from the 

application.Acknowledgements: Thanks to Ingemar Wiberg (ScandiDos AB, 

Uppsala, Sweden) for his great support with the Delta4 detector, during the 

measurements as well as the analysis. 

142 oral 

DOSIMETRIC VERIFICATION OF RAPIDARC TM VOLUMETRIC 

MODULATED ARC THERAPY 

J. Medin 1 , F. Kjær-Kristoffersen 1 , S. Ceberg 2 , S. Bäck 2 , H. Gustavsson 

2 3 4 5 6 7 

, Y. Archambault , J. Bocanek , L. Cozzi , V. Eberhard , I. Gomola , I. 

Wiberg 8 , S. Korreman 1 

1 

RIGSHOSPITALET, COPENHAGEN UNIVERSITY HOSPITAL, Radiation 


2 

MALMÖ UNIVERSITY HOSPITAL, Medical Physics, Malmö, Sweden 

3 

VARIAN MEDICAL SYSTEMS, Las Vegas, NV, USA 

4 

VARIAN MEDICAL SYSTEMS INTERNATIONAL AG, Zug, Switzerland 

5 

ONCOLOGY INSTITUTE OF SOUTHERN SWITZERLAND, Radiation Oncology, 

Medical Physics Unit, Bellinzona, Switzerland 

6 

PTW, Freiburg, Germany 

7 

IBA DOSIMETRY, Schwarzenbruck, Germany 

8 

SCANDIDOS AB, Uppsala, Sweden 

Purpose: Recently, Varian Medical Systems have announced the introduction 

of a new treatment technique to perform volumetric modulated arc ther-


apy (RapidArc TM ). With this technique the absorbed dose is delivered during 

a single gantry rotation using variable MLC positions, dose rate and gantry 

speed. A preclinical installation of the RapidArc beam delivery approach was 

carried out on a Varian Clinac at Rigshospitalet in Copenhagen. The purpose 

of the installation was to perform measurements in order to verify the 

correctness of absorbed doses delivered with the RapidArc technique. 

Materials: Several treatment plans were generated in the Eclipse preclinical 

version of the RapidArc optimizer including H&N, prostate, and lung. The 

various plans were delivered and measured with four different dosimetric systems; 

IBA I’mRT MatriXX with MULTICube, PTW 2D-ARRAY seven29 with 

OCTAVIUS, Scandidos Delta4, and polymer gel. Using the polymer gel detector, 

a high spatial resolution of the measurement together with volumetric 

analysis were obtained. All plans were delivered several times, which allowed 

a comparison between measured and calculated absorbed doses together 

with a verification of the consistency of the delivery. Gamma analysis (acceptance 

criteria 3%/3mmDTA) was used to verify the correspondence between 

dose distributions. The temporal resolution of the delivery was analysed by 

investigating the arc segments between control points (177 control points per 

rotation) separately. 

Results: Overall, good agreement was observed between measured and calculated 

absorbed doses in most cases with gamma values below 1 in >95% 

of the measured points. The reproducibility of delivery was found to be very 

high. Gamma analysis between two consecutive runs of the same delivery 

plan generally showed gamma values above 1 in less than 1% of the measured 

points. Temporal analysis showed some discrepancies between doses 

delivered between control points (~2 degrees of the rotation) in consecutive 

runs of a plan, however these were cancelled out in the accumulated absorbed 

dose in the cases investigated. 

Conclusions: The delivery of RapidArc therapy has been verified to correspond 

well with calculated absorbed dose distributions for a number of different 

cases. The delivery was found to be reproducible, and carried out with 

high stability of the accelerator performance. 

143 oral 

EVALUATION OF THE TPS OF TOMOTHERAPY IN SMALL LUNG TU- 

MORS USING TOMOPEN, THE FIRST MONTE CARLO TREATMENT 

PLANNING FOR TOMOTHERAPY 

E. Sterpin 1 , G. Olivera 2 , S. Vynckier 3 

1 

UCL - SAINT-LUC UNIVERSITY HOSPITAL, Radiotherapy, Brussels, 

Belgium 

2 

TOMOTHERAPY INCORPORATED, Department of Research, Madison, WI, 

USA 

3 

SAINT-LUC UNIVERSITY HOSPITAL, Radiotherapy, Brussels, Belgium 

Purpose: Evaluate the accuracy of the TPS of Tomotherapy in inhomogeneous 

phantoms and lung tumors using TomoPen, an accurately benchmarked 

Monte Carlo (MC) model of helical Tomotherapy 

Materials: The convolution/superposition (C/S) algorithm delivered by Tomotherapy 

is based on the collapsed-cone approximation. This approximation 

may lead to significant deviations in inhomogeneous media. TomoPen is 

a previously validated MC model of helical Tomotherapy (Sterpin et al 2008). 

Its validity should therefore not be limited by the presence of inhomogeneities. 

For the phantom study, static fields with sizes of 0.6x2.5, 2.5x2.5 and 10x2.5 

cm were used. This phantom was made with three slabs (2 cm thick each) 

of water-like density material separated two by two with 7 cm thick slabs with 

a varying density set to three possible values (ρ = 0.1, 0.25, 0.4 g/cm). The 

accuracy of C/S was evaluated by comparing dose distributions calculated 

with C/S and TomoPen. For one value of the density (ρ = 0.25 g/cm), measurements 

with EBT gafchromic films were performed and compared to calculations. 

The clinical part of this study focuses on comparing TomoPen and 

C/S in three lung tumors cases. The tumors were small, with diameters within 

a range of 2 to 5 cm. To ensure a "fair" comparison, all the calculations were 

performed using identical dose grid and dose-volume histogram (DVH) computation 

engine. 

Results: In the phantom study, a good agreement was generally achieved 

between TomoPen, C/S and measurements (for ρ = 0.25 g/cm) for lateral 

profiles, with deviations within 2% /1 mm, proving that the C/S algorithm accounts 

for loss of lateral equilibrium effects. For depth dose distributions, 

good agreement was also achieved when ρ = 0.4 and 0.25 g/cm with deviations 

within 3%. However, in the most extreme case (ρ = 0.1 g/cm), differences 

between TomoPen and C/S could reach 10% of the maximum dose. In 

the clinical study, deviations up to 3% could be observed for the mean dose to 

the target volume as shown in the figure where dose distributions and DVHs 

are compared for one small lung tumor case (3 cm diameter). In this example, 

C/S significantly predicted higher dose coverage of the target volume (PTV) 

than TomoPen, whereas no visible difference was observed for the right lung. 

Conclusions: Those results proved the ability of the C/S algorithm to compute 

the dose in inhomogeneities with reasonable accuracy but demonstrated 

also the potential of introducing TomoPen in clinical practice, especially for extreme 

cases such as small lung tumors. 

Treatment of cancer in the thoracic region 

144 oral 

THREE-DIMENSIONAL CONFORMAL VERSUS DIRECT APER- 

TURE OPTIMISATION-BASED INTENSITY MODULATED BREAST 

CONSERVING RADIOTHERAPY INCLUDING SIMULTANEOUSLY 

INTEGRATED BOOST 

H. P. van der Laan 1 , W. Dolsma 1 , J. Maduro 1 , E. Korevaar 1 , H. 

Langendijk 1 

1 UNIVERSITY MEDICAL CENTER GRONINGEN / UNIVERSITY OF GRONIN- 

GEN, Department of Radiation Oncology, Groningen, Netherlands 

Purpose: The main purpose was to investigate the possible reduction of dose 

delivered to organs at risk (OAR) in three-dimensional conformal breast conserving 

radiotherapy with simultaneously integrated boost (3D-CRT-SIB) by 

application of various strategies for direct aperture optimisation-based intensity 

modulated radiotherapy SIB (IMRT-SIB). Second, we tried to identify pretreatment 

factors that could be used to identify patients which benefit most 

from IMRT-SIB. 

Materials: Thirty patients with early-stage left-sided breast cancer that were 

treated with 3D-CRT-SIB were selected for this study. Dosimetric results were 

compared to that with ’first acceptable solution’ and ’optimised solution’ IMRT- 

SIB. Two plans were made for each IMRT-SIB solution: 1) a fully segmented 

plan, 2) a plan consisting of conformal open beams delivering 75% of the 

dose to the breast and boost planning target volumes (PTV) and IMRT segments 

delivering the remaining 25%. Patient related factors were tested for 

their ability to predict OAR dose reductions and reduced normal tissue complication 

probability (NTCP) of late cardiac mortality, radiation pneumonitis and 

breast fibrosis with IMRT-SIB, using existing NTCP model parameters derived 

from studies reporting on these complications in breast cancer patients.


Results: Coverage of the PTVs was adequate for each plan and each patient. 

IMRT-SIB significantly reduced the dose delivered to the heart and lungs, volumes 

receiving ≥95% and ≥107% of the prescribed breast dose, and as 

shown in the table, NTCP of cardiac mortality and breast fibrosis, when compared 

to 3D-CRT-SIB. Smaller differences were found between the various 

IMRT-SIB strategies. The overlap between heart and breast planning target 

volume in tangential beam’s-eye-view was significantly associated with reduced 

proportions of heart receiving ≥30 Gy and reduced probability of late 

cardiac mortality with IMRT-SIB as compared to 3D-CRT-SIB. Boost volume 

was significantly associated with reduced lung dose and reduced volumes 

receiving ≥107% of the prescribed breast dose. Boost location was significantly 

associated with reduced lung dose, reduced volumes receiving ≥95% 

of the prescribed breast dose and breast fibrosis. 

Conclusions: IMRT-SIB reduces dose delivered to heart, lungs and glandular 

breast tissue beyond the levels obtained with 3D-CRT-SIB. Furthermore, 

potential reductions of OAR dose and NTCP depend on specific patient related 

factors. These allow selection of patients for IMRT-SIB. 

145 oral 

IMPACT OF SEROMA REDUCTION ON BREAST BOOST VOLUME 

IRRADIATION 

D. Minkema 1 , A. van Mourik 1 , C. Hurkmans 2 , P. Elkhuizen 1 , C. van 

Vliet-Vroegindeweij 1 

1 THE NETHERLANDS CANCER INSTITUTE/ ANTONI VAN LEEUWENHOEK 

HOSPITAL, Radiation Oncology, Amsterdam, Netherlands 

2 CATHARINA HOSPITAL, Eindhoven, Netherlands 

Purpose: CT based planning of a boost for breast RT requires accurate definition 

and delineation of the target volume, i.e. excision cavity. Volume reduction 

of the excision cavity as a consequence of shrinking seroma in the 

course of treatment is disregarded in single CT planning. Hence, a larger 

boost volume may be irradiated than necessary. To compensate for this effect, 

sequential boost (SEQ) strategies with a second CT scan for the boost 

plan might be used. Similarly, though less effectively, simultaneous integrated 

boost (SIB) techniques may be replanned halfway through treatment. The 

purpose of this multi-institutional study is to investigate seroma reduction and 

to see if this effect can be used to improve breast RT. 

Materials: CT scans of 37 patients (stage T1-2 invasive breast cancer; breast 

conserving surgery followed by SIB/SEQ RT; CT prior to RT & CT during RT) 

were used in this study. The excision cavity including seroma was delineated 

on both CT-scans by a radiation technologist and reviewed by a radiationoncologist 

(PE). A CTV was generated in the conventional way. CTV differences 

(CTVdiff (cm3, %)) between first and second CT scan were computed. 

Linear regression of days between surgery and first CT (dayss-ct) and initial 

CTV volume (CTVinit (cm3)) was performed on this difference. 

Results: Absolute and relative seroma reductions are both inversely correlated 

with the time lapse between surgery and first CT (see Table 1). CTVinit 

predominantly determines absolute CTV reduction, but is no indicator for relative 

reduction. No evidence was found to suggest that CTV reduction was 

more pronounced below certain dayss-ct or CTVinit thresholds. Note that the 

range of dayss-ct in this study was limited. 

Conclusions: The time interval between surgery and CT as well as initial 

CTV volume are important factors in CTV volume reduction. Taking this into 

account, a SIB might best be chosen in case of larger surgery-RT intervals, 

in combination with replanning. Patients with large initial CTVs benefit more 

from a SEQ with repeated CT during RT. In general, SIBs have a tighter 

total dose distribution, but when taking the seroma effect into consideration 

the breast volume receiving a high dose might not be smaller compared to 

SEQ. To further substantiate these findings a planning study needs to be 

performed. 

146 oral 

S 49 

COMPARATIVE DOSIMETRIC STUDY OF PHOTON AND ELECTRON 

BOOST TECHNIQUES USING COMPUTED TOMOGRAPHY GUIDED 

TARGET DEFINITION AND PLANNING AFTER BREAST CONSERV- 

ING THERAPY 

G. Mitera 1 , M. Davidson 2 , M. Cardoso 1 , J. P. Pignol 1 

1 ODETTE CANCER CENTRE, Radiation Oncology, Toronto, Canada 

2 ODETTE CANCER CENTRE, Radiation Physics, Toronto, Canada 

Purpose: To investigate the dosimetric impact of photon and electron boost 

techniques after breast conserving therapy using computed tomography 

(CT)-based target definitions and 3D planning. The aim of this study was to 

compare dose distributions for each type of boost in terms of target coverage 

and dose delivered to organs at risk. 

Materials: Fourty one patients who had undergone CT simulation for whole 

breast radiotherapy after breast-conserving surgery to the left breast were included 

in the study. Treatment plans were generated to deliver 50 Gy to the 

whole breast using a multi-segmented forward intensity modulated radiotherapy 

approach. Post-surgical cavities, as seen on CT were contoured to create 

the clinical target volume (CTV). For photon boosts, a 1.5 cm margin added 

to the CTV defined the planning target volume (PTV1). For electrons, the 

dose was specified at the depth of Dmax at the 90% isodose level. An electron 

energy sufficient to provide 85% isodose coverage to the PTV2 (cavity 

plus 2 cm margin) was chosen. Six patients were excluded from the analysis 

as their PTVs could not be adequately covered using the highest available 

electron energy (18 MeV). A dose of 16 Gy was prescribed to the respective 

boost PTVs. To compare the dosimetric impact of boost type, treatment plans 

were generated and dose-volume histograms (DVHs) were generated for the 

’evaluation’ PTVs, heart, left anterior descending artery (LAD) and lungs. The 

’evaluation’ PTV is the portion of the PTV excluding the chest wall and 5 mm 

of skin. 

Results: For the thirty five patients analyzed, a DVH analysis showed that 

the mean PTV receiving 95% of the dose (V95) was equivalent for both the 

photon and electron plans (p=0.49). The differences in DVH parameters for 

the heart, including V40, V30, V5 and V1 were negligible (p>0.13) between 

techniques. However, a significant increase in mean heart dose of 31.2 cGy 

(p=0.035) was observed in electron plans. The mean dose to the LAD was 

on average 58.2 cGy higher using electrons, though not statistically significant 

(p=0.08). Electrons also deposited a higher dose to the lungs on average, 

resulting in a significant increase in DVH parameters such as V20 (5% 

with electrons vs 4.8%), V5 (12.4% vs 10%) and V1(43.3% vs 40.4%). Each 

parameter analyzed for the organs at risk fell within normal tissue dose tolerances. 

Conclusions: Preliminary dosimetric analysis reveals that using photons or 

electrons for boosting breast surgical cavities results in equivalent coverage of 

the target. Although statistically significant differences were observed within 

some dosimetric parameters for the organs at risk, these small differences 

may not be clinically significant. These results suggest that on average, photon 

and electron boosts provide comparable dosimetric outcomes. Further 

stratification of the data (e.g. by CTV size or location) may reveal additional 

trends to allow us to tailor boost techniques appropriately for each patient.


147 oral 

FEASIBILITY OF THREE-DIMENSIONAL CONFORMAL SIMULTA- 

NEOUSLY INTEGRATED BOOST TECHNIQUE WITH REGARD TO 

ACUTE SKIN TOXICITY AND OTHER SIDE EFFECTS IN BREAST 

CONSERVING RADIOTHERAPY 

M. Hollander 1 , H. P. van der Laan 1 , W. Dolsma 1 , J. Maduro 1 , H. 

Langendijk 1 



Purpose: In 2005, we introduced three-dimensional conformal radiotherapy 

with simultaneously integrated boost (3D-CRT-SIB) for breast-conserving 

treatment in early breast cancer. With this technique, dose per fraction to 

the boost was increased from 2.0 Gy to 2.3 Gy and overall treatment time 

was reduced with 8 days. Theoretically, these two factors could result in an 

increase in acute toxicity. Therefore, the purpose of this study was to evaluate 

physician-rated acute skin toxicity and patient-rated side effects during 

treatment with this technique. 

Materials: This was a prospective study and the study population was composed 

of 186 consecutive patients. Acute toxicity was rated by the treating 

radiation oncologist using the CTCAE v3.0 scoring system for radiation dermatitis 

on three occasions (every two weeks) during treatment. Concurrently, 

the patients were asked to fill out the UMCG Radiotherapy Breast Cancer 

Questionnaire (RBCQ). The RBCQ was composed of 17 questions regarding 

side effects, graded at a four point scale as none, a bit, moderate or severe. 

Occurrence of physician-rated acute skin toxicity and patient-rated side effects 

during treatment was analysed. 

Results: As expected, physician-rated acute skin toxicity increased when 

time of treatment elapsed. Furthermore, patient-rated acute side effects 

which were showing an increase during treatment, included most frequently 

reactions of the skin. For example, it was found that physician-rated acute 

skin toxicity and patient-rated redness of the skin was minimal during the first 

weeks of treatment, while after 21 fractions, a significant increased incidence 

of Grade 2 or higher and moderate / severe toxicity was observed, with relative 

risks of 4.1 and 3.1, respectively. However, severe patient-rated side 

effects were rarely seen and only 7% experienced severe redness of the skin 

in the last week of treatment. Moreover the maximum physician-rated acute 

skin toxicity was Grade 3 in only 2% of the patients and Grade 2 in 34%. The 

table shows physician-rated acute skin toxicity and the most frequently seen 

patient-rated side effects in the last week of treatment. 

Conclusions: The most frequently seen toxicities during treatment were skin 

toxicities. Severe side effects were rarely reported and 36% of the patients 

had a physician-rated acute skin toxicity of Grade 2 or higher. Therefore, 

3D-CRT-SIB as employed in our institution seems to be well tolerated and 

feasible with respect to acute skin toxicity and treatment related side effects. 

148 oral 

RESPIRATORY GATED RADIOTHERAPY FOR DAILY ROUTINE: 2 

YEARS CLINICAL EXPERIENCE FROM THE RTT’S PERSPECTIVE 

S. Genhart 1 , C. Siegrist 1 , C. von Briel 1 , P. Cossmann 1 

1 INSTITUTE FOR RADIOTHERAPY, CH 5000 Aarau, Switzerland 

Purpose: Respiratory gated treatment using the Varian RPMgating system 

offers the possibility to apply radiation therapy under breathing control. Since 

2 1/2 years we are treating all breast and lung cancer patients with such a 

system. The aim of this study was to evaluate the properties of such systems 

with regard to a clinical use in daily routine. 

Materials: The vertical motion of an external marker box, i.e. the breathing 

excursion, is tracked by an infrared sensitive video-camera-based hardware. 

The system is used for acquisition of the CT-Scan (4D-CT) as well as the 

treatments; for the latter it manages the controlled switching of the radiation 

beam during a pre-selected specific phase of the respiratory cycle. In order 

to achieve a stable and regular breathing pattern the patient receives digital 

breathe-in/breathe-out commands from the gating system via loudspeakers 

called audio coaching in the CT-room and treatment room. Furthermore a 

self-developed integrated biofeedback-system called video coaching - shows 

the patient the actual breathing curve on a table mounted monitor. For the 

treatment the patient has the choice between free breathing and voluntary 

end inspiration breath-hold. 

Results: Patients have to be audio-coached using their fixed individual inhale 

and exhale duration as well as breathing amplitude which have to be 

determined prior to the CT acquisition within a separate coaching session. 

The whole coaching process at the CT scanner may need up to 30 min, depending 

on the patient’s compliance. The 4DCT-acquisition is approx. 15 min 

long. Chosen gating thresholds mostly vary between 90% and 50% of the 

maximum amplitude. Correspondingly this leads to duty cycles and thus to 

a prolongation of the beam-on time by a factor of up to 3. Hence the time 

slot needed for a two-field breast treatment including setup control using onboard-imaging 

increases from 10 up to 15 min for free-breathing, whereas 

voluntary breath-hold allows still a 10 min slot. 

Conclusions: Our experiences indicate that audio and video coached gating 

can be used in daily routine. Only in some rare cases a gated treatment is 

hardly or even not possible. Video-coaching in our opinion is indispensable 

for clinical routine as it optimizes the quality of CT data. It significantly decreases 

an overshooting and/or undershooting of the thresholds and hence 

limits unacceptable treatment prolongation, which occurs when the patients 

are only audio-coached. 

149 oral 

CLINICAL IMPLEMENTATION OF VOLUMETRIC INTENSITY MODU- 

LATED ARC THERAPY (VMAT) 

H. McNair 1 , A. Aitken 1 , J. Bedford 2 , J. Brock 1 , S. Helyer 3 , A. Warrington 

2 , M. Brada 4 

1 

ROYAL MARSDEN NHS FOUNDATION TRUST AND INSTITUTE OF CANCER 

RESEARCH, Radiotherapy, Sutton, United Kingdom 

2 


RESEARCH, Joint Department of Physics, Sutton, United Kingdom 

3 

ROYAL MARSDEN NHS FOUNDATION TRUST, Radiotherapy, Sutton, United 

Kingdom 

4 


RESEARCH, Academic Unit of Radiotherapy, Sutton, United Kingdom 

Purpose: VMAT is a development of IMRT and allows highly conformal treatment 

plans to be delivered with increased efficiency. IMRT is routinely delivered 

at the Royal Marsden Hospital and VMAT is a logical progression. The 

changes in treatment delivery and verification, were first implemented and 

tested in a patient who received adjuvant RT for small cell lung cancer using 

conventional margins and dose 

Materials: The patient was immobilised using a lung board; CT scans were 

acquired with a Philips Brilliance Big Bore CT scanner. The treatment was 

inverse planned using AutoBeam v4.6 in-house software and transferred to 

Philips Pinnacle3. A single coplanar clockwise arc starting at gantry angle 

190a and finishing at gantry angle 170a was defined. The arc consisted of 35 

control points at 10a gantry intervals. The MLC movement between control 

points was limited to allow the gantry to rotate at close to maximum speed of 

6a/s. The treatment was delivered to a dose of 50 Gy in 25 fractions using 

MOSAIQ version 1.41, an Elekta Precise linac and verified with Synergy cone 

beam CT using a No Action Level off line protocol. 

Results: 23 fractions of radiotherapy were successfully delivered with VMAT. 

Two fractions were delivered using a standard conformal plan when the VMAT 

linac was unavailable. The treatment time was 90 secs for the VMAT plan and 

180 secs for the conformal plan. The systematic and random set up errors 

were 1.8 mm (3.5 mm), 1.2 mm (3.1 mm) and 1.8 mm (1.2 mm) in right-left, 

superior-inferior and anteriorposterior directions respectively. 

Conclusions: We have successfully treated the first patient with VMAT. The 

efficient delivery of such highly localized treatment has potential for hypofractionated 

treatments such as SBRT. 

Quality of Life 

150 oral 

THE FIRST PROSPECTIVE STUDY COMPARING SHORT-COURSE 

AND LONG-COURSE RADIOTHERAPY FOR LOCAL CONTROL OF 

METASTATIC SPINAL CORD COMPRESSION 

D. Rades 1 , M. Lange 1 , T. Veninga 2 , L. Stalpers 3 , A. Bajrovic 4 , V. Rudat 

5 , S. Schild 6 , J. Dunst 1 

1 

UNIVERSITY HOSPITAL SCHLESWIG-HOLSTEIN, Radiation Oncology, 

Luebeck, Germany 

2 

DR. BERNARD VERBEETEN INSTITUTE, Radiation Oncology, Tilburg, 

Netherlands 

3 

ACADEMIC MEDICAL CENTER, Radiation Oncology, Amsterdam, Nether-


lands 

4 

UNIVERSITY MEDICAL CENTER HAMBURG-EPPENDORF, Radiation 

Oncology, Hamburg, Germany 

5 

SAAD SPECIALIST HOSPITAL, Radiation Oncology, Al Khobar, Saudi Arabia 

6 

MAYO CLINIC SCOTTSDALE, Radiation Oncology, Scottsdale, USA 

Purpose: This study (SCORE = Spinal Cord cOmpression Recurrence Evaluation) 

is the first prospective study that compared short-course RT and 

long-course RT for local control (LC) of metastatic spinal cord compression 

(MSCC). 

Materials: The study compared short-course RT with 1x8 Gy or 5x4 Gy given 

in

S 52 AWARD LECTURE MONDAY, SEPTEMBER 15, 2008 

tocol (p=0.0004), wiht an earlier onset with hyperfractionated and combined 

conventional-hyperfractionated schedules. Univariate comparison, with regard 

to incidence as well as latency of mucositis grade 2 or 3, did not reveal 

any significant differences between dexpanthenol vs. water mouth washes 

within the radiotherapy protocols as well as for the entire population. In a 

multivariate analysis, using radiotherapy protocol, dexpanthenol administration 

and mechanical cleansing as independent parameters, only the effect of 

the radiotherapy protocol was significant (p

TUESDAY, SEPTEMBER 16, 2008 TEACHING LECTURE 

Tuesday, September 16, 2008 


158 speaker 

SCREENING, PREVENTION AND VACCINATION FOR CERVICAL 

CANCER 

T. Iftner 1 

1 UKT, Sektion Experimentelle Virologie, Tuebingen, Germany 

Cervical cancer has been recognized as a rare outcome of a common sexually 

transmitted infection. The etiological association is restricted to a limited 

number of so called "high risk" human papillomavirus types. The association 

is causal in nature and under optimal testing systems HPV DNA can be identified 

in all specimens of invasive cervical cancer. However, only the persistent 

infection with "high risk" Human Papillomavirus types is a necessary cause 

of cervical cancer. Cofactors that modify the risk among HPV DNA positive 

women include the use of oral contraceptives for 5 or more years, smoking, 

high parity (5 or more full term pregnancies) and previous exposure to other 

sexually transmitted diseases such as clamydia trachomatis and Herpes virus 

type 2. Women exposed to the human immunodeficiency virus (HIV) are at 

high risk of HPV infection, HPV DNA persistency and progression of HPV lesions 

to cervical cancer. The main onco-proteins of "high risk" HPV types are 

E6 and E7, which can bind to and degrade cellular tumor suppressor proteins 

like p53 and pRb. In addition, the E6 protein induces the activity of the telomerase 

enzyme and impairs the efficiency of the base excision DNA repair 

pathway. The activity of the E6 and E7 proteins pushes infected cells into the 

S-phase and leads to the accumulation of chromosomal abnormalities and 

centrosome duplications. Two prophylactic vaccines directed against the two 

main high risk types (16 and 18) are now available and show high efficacy to 

prevent persistent infections and cervical disease caused by HPV16/18. However, 

successful therapeutic vaccines and specific antiviral therapies have not 

yet been developed. 

159 speaker 

TARGET VOLUME SELECTION AND DELINEATION IN HEAD AND 

NECK TUMORS: BEYOND ICRU DEFINITION. 

V. Grégoire 1 

1 UNIVERSITÉ CATHOLIQUE DE LOUVAIN, ST-LUC UNIVERSITY HOSPITAL, 

Department of Radiation Oncology, Brussels, Belgium 

Implementation of Intensity Modulated RadioTherapy (IMRT) for head and 

neck tumors requires proper selection of the Clinical Target Volume (CTV) for 

the neck nodes and the primary tumors, and accurate 3D delineation of these 

selected volumes.For CTV selection and delineation in the N0 neck, collaborative 

works between radiation oncologists, surgeons and radiologists led 

to the publication in 2004 of consensus recommendations for the delineation 

of levels I to VI (R&O, 69: 227-236, 2003). DAHANCA, EORTC, GORTEC, 

NCIC and RTOG have endorsed these new recommendations. The use of a 

unique set of unambiguous and easily identifiable boundaries should limit the 

variability in CTV delineation in the neck and hence contribute to increase homogeneity 

in treatment delivery.More recently, these recommendations have 

been revisited for the node positive neck (R&O, 79: 15-20, 2006). In a nutshell, 

cranially, it is recommended to include the retro-styloid space up to 

the base of skull. In case of nodal involvement in level IV and/or Vb, it is 

also recommended to include the sub-clavicular fossae. When a node abuts 

a non-lymphatic structure (e.g. the SCM) or present extracapsular extension 

(based on imaging or pathological assessment), it is recommended to include 

this structure into the CTV in the entire invaded level. In the post-operative 

situation, in addition to the recommendations outlined above, the CTV should 

always include the entire operative bed including all tissue volume with radiological 

evidence of fibrosis and edema. For primary tumors, the selection 

of the CTV is a far more complex issue, which remain mainly unresolved. A 

general principles that should govern the elaboration of recommendations for 

the selection of primary tumor CTV is that the microscopic spread of squamous 

cell carcinomas follows anatomical compartments (e.g. para-laryngeal, 

para-pharyngeal, pre-epiglottic spaces) bounded by anatomical barriers (e.g. 

bone cortex, muscular facia, ligaments). Unless transgressed, such barriers 

would limit the local primary tumor spread. 

160 speaker 

3D IMAGE GUIDED BRACHYTHERAPY IN HEAD AND NECK 

CANCER. TECHNIQUES AND BENEFITS 

V. Strnad 1 

1 UNIVERSITY HOSPITAL ERLANGEN, Dept. of Radiation Oncology, Erlangen, 

Germany 

Introduction: The most often technique using for brachytherapy of head neck 

S 53 

cancer is the multicatheter interstitial technique. During last decades the insertion 

of plastic tubes is usually has been made based on traditional clinical 

information’s as palpation, inspection and panendoscopy. There is little 

experience with the use of modern imaging techniques as CT-, MRI- or PET- 

CT-imaging for modern Image Guided Interstitial Brachytherapy for head and 

neck tumours. Principal it is possible to use all images as furthermore information’s 

for Image Guided Brachytherapy besides the X-ray imaging. The 

imaging techniques have to meet the highest requirements for good identification 

of tumor, of encompassing soft tissue and of bone structures. Also it 

should be possible to reconstruct the implanted plastic tubes with maximum 

accuracy and thus to have the possibility to make a quantitative and qualitative 

analysis of the dose distribution, DVH etc. 

Methods: The X-ray imaging is today an obsolete imaging modality for Image 

Guided Interstitial Brachytherapy. Surely it allows doubtless a good catheter 

reconstruction, but no information’s are available about soft tissue and tumor 

bulk. In contrast to it the CT imaging in the majority of cases make possible 

to distinguish the tumor bulk, but in case of small tumors and particularly 

in postoperative cases (only surgical scare is present!) no or very limited 

information’s are present about the tumor size. Additionally metal artifacts’ 

(teeth-fillings) hamper to distinguish the correct size and form of tumor bulk. 

Nearly the same limitations presents the MR-imaging (the teeth-fillings leads 

to effacements of MR-signal), but the diversity of soft tissue imaging is among 

all imaging methods the best. The PET-CT eliminate to a certain extent the 

not sufficiently information’s of CT. First of all we can imagine with PET-CT the 

metabolic active part’s of tumor and in this way additionally localize some part 

of tumor. But also using PET-CT for Image Guided Interstitial Brachytherapy 

it is necessary be aware PET-CT shows us also soft tissue injury (particularly 

misleading PET hot signal due early surgical injury) or inflammation as "hot 

signal" and it is also to keep in mind that the not metabolic active parts of 

tumor or very small tumors are not visualized. The efficacy and side effects 

of interstitial multicatheter LDR- and PDR-brachytherapy for head and neck 

tumors are very good documented in a lot of clinical studies. The local control 

rates are between 80-90% or better. The probability of serious side effects 

such soft tissue necrosis or osteoradionecrosis is nowadays in "centers of 

excellence" below 5% - particularly thanks to the Image Guided Interstitial 

Brachytherapy. 

Conclusion: All modern imaging modalities such CT, PET-CT and MRI can 

support the interventional radiation oncologist, but can not replace his clinical 

feeling. The finger and eye of the surgeon is by nothing to replace. Image 

Guided Interstitial Brachytherapy for head and neck tumours’ is a treatment 

option with excellent efficacy and negligible side effects for carefully selected 

patients. If done properly, the interstitial brachytherapy alone or as boost is 

safe and delivers a dose that is higher and more conformal than what can be 

achieved by external beam radiation alone. 

161 speaker 

NEW DEVELOPMENTS IN CELL DEATH: AUTOPHAGY, SENES- 

CENCE AND THE REST 

M. Pruschy 1 

1 UNIVERSITY HOSPITAL ZÜRICH, Department of Radiation Oncology, 

Zurich, Switzerland 

During the last decade major research efforts in ionizing radiation (IR)induced 

cell death focused on the study of IR-induced apoptosis and mitotic 

cell death. Though other modes of IR-induced stress responses leading 

to different modes of (programmed) cell death have been identified during 

the last years, including IR-induced autophagy, senescence and even necrosis. 

The mode of cell death induced by IR depends on the amount and 

quality of DNA damage, the DNA damage response, and the induction of 

DNA-damage-independent cellular stress responses. Eventually the different 

modes of IR-induced cell death can also differ widely amongst different 

tumor and normal cell types and depend on their genetic background. We 

will give an overview on the major cellular processes and pathways related to 

IR-induced autophagy, senescence and necrosis, and present how they can 

be distinguished at the molecular and morphological level. Importantly these 

programmed forms of cell death are differently activated and are frequently 

altered in cancer and therefore also contribute to variations in radiosensitivity 

amongst tumor cells. We will discuss the impact of these newly identified 

modes of cell death for loss of clonogenicity and present early attempts to exploit 

these different modes of cells death to overcome treatment resistances 

as part of combined treatment modalities with ionizing radiation and antisignaling 

agents.

S 54 TEACHING LECTURE TUESDAY, SEPTEMBER 16, 2008 

Multimodality imaging and registration 

162 speaker 

MULTIMODALITY IMAGING AND REGISTRATION 

M. Kessler 1 

1 UNIVERSITY OF MICHIGAN, Department of Radiation Oncology, Ann Arbor 

MI, USA 

Accurate target delineation and image guidance are essential components in 

modern radiotherapy. The definition of the gross tumor volume (GTV) and 

specification of appropriate margins around the GTV dictate the maximum 

radiation doses that may be safely delivered. Ongoing developments in multimodality 

and 4D imaging technologies are providing opportunities to improve 

tumor localization and patient modeling for treatment planning and to reduce 

setup variations and PTV margin size for treatment delivery. Proper use of 

these technologies can provide greater sparing of dose to normal tissues and 

permit safer escalation of tumor doses. Imaging techniques are also being 

developed to help predict response to treatment during therapy when interventions 

and adaptations are still possible. Optimal use of these technologies 

requires tools to spatially register multimodality and time series image data, 

and once registered to transfer and integrate anatomic, functional and dosimetric 

information from the different imaging studies.Modern treatment planning 

and treatment delivery systems do provide some form of these tools, 

though most support only simple geometric models with very few degrees of 

freedom (DOF), usually global rigid transformations (e.g., three rotations and 

three translations). Unfortunately, accurate registration of image data from 

clinical sites other than the brain or limited anatomic regions requires many 

more degrees of freedom to properly model deformation, sliding of tissues, 

and changes in tumor size and patient weight between or during imaging 

studies and treatment fractions. The situation is further complicated by the 

realization that the optimal number of DOF and other registration parameters 

vary from tissue to tissue; using too few or too many DOF or inappropriate 

parameters can cause inaccurate or unphysical results. Fortunately, 

development of sophisticated image registration algorithms which accommodate 

common anatomic and physiologic processes is a very active area of 

research and promising techniques are emerging and undergoing clinical validation. 

As with any new technology introduced in the clinic, many obstacles 

must be overcome before widespread adoption can occur. This lecture will 

describe the current state of this technology and provide examples of the 

opportunities and challenges ahead. 

163 speaker 

DOSE VERIFICATION IN ADVANCED RADIATION THERAPY - NEW 

ESTRO BOOKLET 

M. Karlsson 1 , A. Ahnesjö 2 , D. Georg 3 , T. Nyholm 1 , J. Olofsson 1 

1 

UNIVERSITY OF UMEÅ, Radiation Sciences, Umeå, Sweden 

2 

NUCLETRON SCANDINAVIA AB AND UPPSALA UNIVERSITY, Section of 

Oncology, Uppsala, Sweden 

3 

MEDICAL UNIVERSITY VIENNA, Department of Radiotherapy, Vienna, 

Austria 

Radiation therapy and treatment planning has gradually increased in complexity 

and manual procedures for independent dose verification can in many 

cases not be properly performed today. Legal demands on independent dose 

verification are regulated by the EURATOM directive 97/43. A task group has 

been assigned by ESTRO for further analysis of independent dose verification 

and its implications for advanced radiation therapy. Estimations of clinical 

outcome and risk for side effects should always be used as baseline for dosimetric 

tolerance limits and action limits. An evaluation of methods presented 

in the literature used to define action limits for the individual patient shows the 

need of a more strict formalism for this purpose. It was further realized that 

systematic deviations and trends of dose variations within the action limits 

may serve as important quality indicators of the treatments delivered clinically. 

To obtain these quality indicators all deviations should be collected both 

in a local database, and into a common "global database" for shared access 

of statistical results. The action limits employed in the QA-procedure are set 

to ensure that the clinical tolerance limits will not exceed a specified risk. In 

order to set proper action limits the uncertainty of the verification tool must be 

known. However, proper setting of the action limits may result in unrealistic 

limits of accepted dose deviation if the uncertainty of the verification tool is too 

large. An independent dose calculation tool should ideally be accurate, easy 

to commission with independent beam data, simple to handle, and be thoroughly 

verified with respect to resulting uncertainty. Published models of the 

photon fluence in the treatment head show that the uncertainty in beam fluence 

modelling can in general can be performed with an accuracy better than 

1SD = 1%. For the dose calculation in the patient geometry several types 

of pencil beam models and point kernel models can be found in the literature. 

A method suggesting that TPR20,10 should be used as the only beam 

quality specification will significantly reduce the measurements needed. If a 

correction method for off-axes softening is applied on that model, the total 

1SD-uncertainty in the dose calculation can be kept below 2% for most beam 

geometries, including the uncertainty in the treatment head modelling. 

164 speaker 

EVIDENCE BASED MEDICINE: GI TUMOURS 

D. Sebag-Montefiore 1 

1 ST JAMES’S INSTITUTE OF ONCOLOGY, Department of Radiation Oncology, 

Leeds, United Kingdom 

The management of gastrointestinal cancer has been defined by a large body 

of evidence from clinical research. This teaching session will focus on research 

involving the use of radiation with or without concurrent chemotherapy 

in the initial treatment of gastrointestinal cancer with the emphasis on rectal 

and anal cancer. In rectal cancer the major focus has been testing the role of 

adjuvant radiotherapy used either pre-operatively or post-operatively. There 

are three key meta-analyses that have evaluate the randomised controlled 

trials [Lancet. 2001:358:1291-304; Jama. 2000 284:1008-15; Cochrane 

Database Syst Rev. 2007(2):CD002102]. All conclude that adjuvant radiotherapy 

reduces the risk of local recurrence but there are differing conclusions 

with respect to cancer specific and overall survival. The differences between 

the three studies will be discussed. New studies have recently reported, including 

the MRC CR07 trial [JCO Part I. Vol 24, No. 18S 3511, 2006 abstract] 

and the implications of this new data with respect to the current evidence 

will be presented.Two pivotal trials [N Eng J Med 2006;355(11):1114-23.; J 

Clin Oncol 2006;24(28):4620-5] have established that pre-operative concurrent 

chemoradiation (CRT) is superior to long course radiotherapy alone with 

respect to local recurrence but without any significant improvement in disease 

free survival. Two further trials warrant discussion - the German study 

that compared pre-operative CRT versus post-operative CRT [N Engl J Med 

2004;351(17):1731-40] and the Polish trial that compared short course preoperative 

RT versus pre-op CRT [Br J Surg 2006;93(10):1215-23]. A further 

important question is whether pre-op CRT can improve the rate of sphincter 

preserving surgery and a recent overview of the phase III evidence (both 

direct and indirect) will be discussed [Radiother Oncol 2006;80(1):4-12.]. A 

key aspect of the presentation will be to discuss the international impact of 

the trials and their influence on clinical practice. Current areas of remaining 

uncertainty will also be highlighted with a view on the important of future clinical 

trial design.Despite the rarity of the disease, anal cancer is an excellent 

example of the evolution of the evidence base from a case report, through 

phase II studies to pivotal phase III trials. CRT is considered the standard 

approach and the supporting evidence is consistent and impressive. Two 

trials established the superiority of Mitomycin C, 5fluoruracil and RT (MMC 

5FU RT) over radiation alone [Lancet 1996;348:1049 1054; J Clin Oncol 

1996;14:2527 - 2539] and one trial showed MMC 5FU RT to be superior to 

5FU RT [J Clin Oncol 1997;15:2040-2049]. Two recent phase III trials set out 

to test whether cisplatin was superior to MMC when combined with 5FU RT. 

One study has recently reported [JAMA. 2008 Apr 23;299(16):1914-21] no 

evidence of any benefit for cisplatin compared to MMC and the current UK 

ACT 2 study is close to its target recruitment of 950 patients. The two trial 

designs of the most recent studies evaluating cisplatin will be compared and 

potential design weaknesses discussed. The presentation will also highlight 

important previous ph II data [Am J Med. 1985 Feb;78(2):211-5] that suggest 

that studies reducing treatment intensity are required in patients with early 

stage anal cancer.The presentation will conclude with some key observations 

with respect to future trial methadology and the important step from clinical 

trial results to infuencing routine clinical practice.

TUESDAY, SEPTEMBER 16, 2008 SYMPOSIUM 


165 speaker 

HOW TO WRITE/SUBMIT A PAPER 

J. Overgaard 1 

1 AARHUS UNIVERSITY HOSPITAL, Aarhus C, Denmark 


166 speaker 

GETTING YOUR PAPER PUBLISHED; THE TRICKS OF THE TRADE 

J. F. Daisne 1 , M. Koritzinsky 2 , M. Mast 3 , L. P. Muren 4 

1 

CLINIQUE ST. ELISABETH, Department of Radiation Oncology, Namur, 

Belgium 

2 

ONTARIO CANCER INSTITUTE/PRINCESS MARGARET HOSPITAL, University 

Health Network, Toronto, Ontario, Canada 

3 

MEDICAL CENTRE HAAGLANDEN, Department of Radiation Oncology, The 

Hague, Netherlands 

4 

AARHUS UNIVERSITY HOSPITAL, Department of Medical Physics and 

Oncology, Aarhus C, Denmark 

All scientists are evaluated with regard to their publication records, determining 

the success of grant applications and career development. Although high 

quality research forms the cornerstone of a scientific paper, numerous strategic 

decisions need to be made on the path to publication. It is crucial for 

young scientists to rapidly pick up these "tricks of the publication trade" to 

push the editorial decision towards that desirable "Accepted".In this session, 

a panel of four young scientists representing our RT professions will discuss 

publication strategies with the Editor-in-Chief of Radiotherapy & Oncology. 

Together we aim to outline the top strategic mistakes made by submitting authors, 

and how to fix them. Issues to be discussed include: How to select the 

appropriate journal How to prepare papers for this journal How to respond to 

reviewersThe session will also be open for questions from the audience. 

Symposium 

S 55 

Clinical evidence for adjuvant radiotherapy for 

cervix and endometrial cancer 

167 speaker 

RADIOTHERAPY FOR ENDOMETRIAL CANCER: CURRENT EVI- 

DENCE AND TRENDS 

C. Creutzberg 1 

1 LEIDEN UNIVERSITY MEDICAL CENTER, Clinical Oncology, Leiden, 

Netherlands 

Endometrial carcinoma, the most common gynecologic cancer in Western 

countries, is typically a cancer of postmenopausal women between 55 and 

85 years of age. It is usually diagnosed at an early stage, resulting in a favorable 

prognosis, with 5-year overall and cancer-specific survival rates in 

the range of 80-85% and 90-95%, respectively. Pelvic radiotherapy has been 

widely used for many years as adjuvant therapy after surgery for women with 

endometrial carcinoma. Three randomized trials have established the role of 

radiotherapy in intermediate risk endometrial carcinoma; the Norwegian trial 

(1968-74), PORTEC 1 (1990-97) and GOG99 (1987-95). These all demonstrated 

that pelvic radiotherapy (RT) provides a highly significant reduction of 

vaginal and pelvic recurrence, but without a survival advantage. Risk factors 

for recurrence were grade 3 disease, stage 1C and age ≥60 years. From 

the PORTEC-1 trial it was concluded that pelvic RT should only be recommended 

to patients at sufficiently high risk of locoregional recurrence (15% 

or over) to warrant the risk of treatment associated morbidity in order to maximize 

initial local control and relapse-free survival. This has resulted in a clear 

reduction of the indications for pelvic RT. Both in PORTEC-1 and in GOG 99 a 

so-called "high-intermediate risk group" was defined, for which the risk of locoregional 

relapse without RT was over 20%. The recently closed PORTEC 

2 trial is currently evaluating whether pelvic external beam therapy can be 

safely replaced by brachytherapy, with results expected in 2008. As a result 

of these trials there has been a further reduction in the use of adjuvant 

radiotherapy for intermediate-risk disease, and a switch to vaginal brachytherapy. 

The principal challenge now is achieving higher survival rates in women 

with high-risk disease. Women with stage IC grade 3 endometrial carcinoma, 

those with stage IIB and III disease or with serous or clear cell histology have 

a reduced survival rates of 50-60% due to increased rates of distant metastases. 

Pelvic RT continues to be the most effective adjuvant treatment to ensure 

pelvic control. Combination of radiotherapy and chemotherapy seems 

the way forward to reduce the risk of distant metastases and improve survival. 

While trials comparing adjuvant chemotherapy and radiotherapy did 

not show any survival difference, both a RTOG phase II study and the randomized 

NSGO/EORTC trial have suggested improved progression-free and 

overall survival in the in the patient group treated with both chemotherapy 

and radiotherapy. The international collaborative randomized PORTEC3 trial 

investigates both survival benefit and ’cost’ in terms of toxicity and quality of 

life of chemotherapy during and after radiotherapy for patients with high-risk 

endometrial carcinoma. 

168 speaker 

NEOADJUVANT TREATMENT IN CERVICAL CANCER 

G. Thomas 1 

1 TORONTO SUNNYBROOK CANCER CENTER, Department of Radiation 

Oncology, North York, Toronto, Canada 

The use and utility of neoadjuvant and adjuvant therapies in cervical cancer 

is dependent on the modality chosen as definitive treatment and the efficacies 

of each additional treatment. Neoadjuvant chemotherapy (NACT) prior 

to surgery plus or minus subsequent adjuvant therapy is being used in a number 

of countries as "standard therapy" for patients with Stage IB, II-III cervical 

cancer. Theoretically NACT may reduce the volume of pelvic disease improving 

operability and possibly sterilizing nodal disease. One large randomized 

trial has been conducted NACT to definitive irradiation in doses which are 

considered inadequate. This study showed a 5-year survival advantage for 

neoadjuvant chemotherapy followed by surgery vs. radiation (54% vs. 44%, 

Benedetti Panici et al); apparent benefit was confined to those with IB/IIA 

(69% vs.51%) disease and not for stage IIB and III. Unfortunately results on 

both arms of the study were inferior to those reported for concurrent chemoradiation 

(CT/RT) (82% Keys et al) or surgery followed by adjuvant CT/RT (78% 

Peters et al). The ongoing EORTC study 55994 compares NACT to CT/RT 

in Stage IB/IIB disease. Sequential phase II studies examining neoadjuvant 

CT/RT or neoadjuvant CT alone suggests that pathologic complete response 

is significantly higher with CT/RT (50-88% vs. 26%) and relapses fewer. A 

neoadjuvant strategy of CT/RT has not been examined in randomized phase 

III trials. Debate would then occur as to which treatment component is considered 

definitive: is the surgery then adjuvant to CT/RT rather than the reverse. 

This strategy of NACT prior to definitive irradiation has been tested in numerous 

randomized phase III trials. Results are coincident and suggest either 

no benefit or detrimental survival. It is theorized that overall protraction of 

antineoplastic treatment allows accelerated proliferation abrogating possible

S 56 SYMPOSIUM TUESDAY, SEPTEMBER 16, 2008 

benefit to the NACT. This strategy has been abandoned. Most centers have 

abandoned the use of neoadjuvant radiation alone prior to surgery; pelvic 

control rates even with tumours as bulky as 7 cm are over 85% with radiation 

alone and higher with chemoradiation. Reported results are good for 

this strategy but the incremental therapeutic benefit for the routine addition of 

surgery to radiation is unclear. Level I evidence would suggest that definitive 

concurrent CT/RT or surgery followed by adjuvant CT/RT constitute the standard 

of care for Stage IB/IIA disease and concurrent CT/RT the standard for 

Stage IIB and III. 

169 speaker 

EVIDENCE FOR ADJUVANT RADIOTHERAPY IN CERVIX CANCER 

WITH OR WITHOUT DRUGS 

C. J. Orton 1 

1 ST JAMES’S INSTITUTE OF ONCOLOGY, Clinical Oncology, Leeds, United 

Kingdom 

In patients with early stage cervical cancer managed by radical hysterectomy, 

the roles of postoperative radiotherapy and chemotherapy are still being defined. 

Prognostic factors in early stage cervical cancer:There are a number of 

histological prognostic indicators in cervical cancer following radical hysterectomy. 

In early stage disease the larger the tumour, including tumour volume, 

canal length, cervical stromal tumour-free rim and parametrial extension, the 

greater the risk of lymph node metastases. Other prognostic factors include 

the depth of invasion relative to overall wall thickness, lymphovascular space 

invasion (LVSI) and lymph node status. The presence of LVSI correlates with 

the risk of lymph node metastases. In one series, patients with no LVSI, only 

6% had positive lymph nodes, compared with 34% with LVSI; corresponding 

5 year survival is 90% with no LVSI, compared to 60% with LVSI; LVSI 

correlates with local failure. Lymph node status is closely related to stage, 

grade and tumour size. The presence of lymph node micrometastases does 

not appear to affect outcome adversely. The effect of tumour grade is controversial 

as there is no universally accepted grading system, although in one 

series those with poorly differentiated stage 1 tumours had a 5-year survival 

of 41-62% compared to 80-90% for those with well-differentiated lesions. A 

clinical review of outcomes of patients with stage IB, node negative, cervical 

cancer, managed at the Royal Hospital for Women in Sydney1, revealed 

that 87% of recurrences occurred in the central pelvis. Pelvic relapses after 

surgery are salvaged in 15-45% of cases with the use of radiotherapy.High 

risk group:The presence of positive nodes, positive parametria, or positive 

surgical margins is associated with an increased risk of recurrence. The most 

important prognostic factor is the involvement of lymph nodes. Five-year survival 

rates in those with positive nodes vary from 51-78%. The prognosis for 

patients with a single positive lymph node below the common iliac bifurcation 

is similar to that of patients with negative nodes. In contrast, the fiveyear 

survival of patients with positive paraaortic nodes treated with extended 

field radiotherapy is approximately 50%. The involvement of the parametria 

results in a reduction in five-year survival regardless of lymph node status, 

from 86% to 63%. Adjuvant therapy for high-risk disease:Patients with positive 

nodes usually receive radiotherapy. There is now evidence for a benefit 

in survival. A small multi-institutional retrospective study conducted by the 

SGO2 in 1979 revealed that there was a lower incidence of pelvic recurrence 

in the irradiated group but this was countered by an increased incidence of 

distant metastases in the unirradiated group. In 2000, the SGO3 reported 

the results of a randomised controlled trial of women with FIGO stage IA2, 

IB and IIA carcinoma of the cervix found to have metastatic disease in pelvic 

lymph nodes, positive parametrial involvement or positive surgical margins 

at the time of primary radical hysterectomy. Patients were randomised to either 

external pelvic radiotherapy with cisplatin and 5-fluorouracil (two cycles 

given during radiotherapy followed by a further two cycles) or external pelvic 

radiotherapy alone. The three-year survival for the women receiving adjuvant 

chemotherapy plus radiotherapy was 87% compared with 77% for those receiving 

radiotherapy alone. This difference was statistically significant. In a 

subsequent publication4 it was reported that patients who completed three to 

four cycles of chemotherapy had significantly better outcomes than those who 

only completed one or two cycles. These data suggest that there might be 

additional benefit from adjuvant chemotherapy after completion of concomitant 

chemoradiotherapy.Intermediate-risk disease:In 1989, the GOG5 published 

the results of a prospective clinicopathological study of 732 patients 

with stage IB cervical cancer treated by radical hysterectomy and bilateral 

pelvic lymphadenectomy. Of these, 645 patients had no disease beyond the 

cervix and negative paraaortic nodes; one hundred had micrometastases in 

pelvic nodes, but their survival was not significantly different from patients with 

negative nodes. Three independent prognostic factors were identified, including 

tumour size, the presence or absence of LVSI and the depth of tumour 

invasion. There is also evidence that patients with multiple intermediate-risk 

factors may be at greater risk than patients with a single positive node. Although 

patients with negative nodes have a 85-90% survival rate after radical 

surgery, they contribute approximately 50% of treatment failures, with most of 

the failures (70%) occurring in the pelvis.Adjuvant therapy for intermediaterisk 

disease:On the basis of these findings, the GOG6 then conducted a randomised 

controlled trial in which 277 patients with stage IB2 cancers and two 

or more high risk factors were randomised to radical hysterectomy with or 

without postoperative irradiation. 137 were randomised to pelvic radiotherapy 

and 140 had no further treatment. The addition of pelvic radiotherapy reduced 

the risk of recurrence, with a recurrence-free survival of 88% compared with 

79% for the control arm at two years. Although the two arms were equal with 

regards to the three risk factors, it is not clear in which group the recurrences 

occurred, and follow-up was short. There was no significant difference in 

overall survival; 11% died of cancer in the radiotherapy arm, compared with 

18% in the control arm. This equates to a 47% reduction in the risk of recurrence 

with adjuvant radiotherapy. There was 10% non-compliance in the 

radiotherapy group. Severe GOG grade 3-4 gastrointestinal and urinary toxicity 

occurred in 6.2% of patients receiving radiotherapy compared with 1.4% of 

controls. In a later publication7 with a ten-year median follow-up, a significant 

benefit was still evident for radiotherapy in terms of progression-free survival 

but the 30% reduction in the risk of death was only of borderline statistical 

significance.Conclusions:Although cross-sectional imaging cannot be used 

to alter the FIGO stage, the information gained from the pre-treatment evaluation 

of cervical cancer is increasingly important in determining treatment 

options. Magnetic resonance imaging (MRI) allows the integrity of the cervical 

stromal ring, involvement of the parametria, and the presence of enlarged 

or suspicious pelvic and paraaortic lymph nodes to be assessed, together 

with visualisation of the renal tract. There is concern that the combination 

of surgery followed by radiotherapy, with or without concomitant chemotherapy 

results in increased treatment related morbidity. There is therefore a 

strong case for avoiding surgery in those patients who are identified preoperatively 

to have high risk factors on MRI. However, it recognised that there 

are a number of patients in whom this is not possible because of lack of 

resources, or by virtue that these factors are not detected or recognised preoperatively. 

In the future it is likely that positron emission tomography (PET) 

in conjunction with CT scanning, will be used to evaluate patients prior to 

treatment. In high-risk patients the role of adjuvant chemoradiotherapy is 

established. In intermediate-risk patients, radiotherapy reduces the risk of recurrence; 

given the evidence supporting the superiority of chemoradiotherapy 

over radiotherapy, there is increasing credence to offer chemoradiotherapy to 

this group of patients. Presently, the most common chemotherapy regimen 

is weekly cisplatin. More than one-third of patients who recur will present 

with extra-pelvic disease. There is increasing interest in the role of adjuvant 

chemotherapy following primary surgery for early stage disease and definitive 

chemoradiotherapy for more advanced disease. Presently, the results from 

systemic treatments are disappointing and there is optimism for the addition 

of newer biological agents to standard chemotherapy.References:1. Kridelka 

FJ, Adjuvant small field pelvic radiation for patients with high-risk stage IB 

node negative cervical cancer after radical hysterectomy and pelvic lymph 

node dissection: a pilot study. Cancer 199; 86:2059-20652. Morrow CP, Is 

pelvic radiation beneficial in the postoperative management of stage IB squamous 

cell carcinoma of the cervix with pelvic node metastases treated by 

radical hysterectomy and pelvic lymphadenectomy? Gynecol Oncol. 1980, 

10:1053. Peters WA, Concurrent chemotherapy and pelvic radiation therapy 

compared with pelvic radiation therapy alone as adjuvant therapy after 

radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol. 

2000 Apr; 18(8):1606-13.4. Monk BJ, Rethinking the use of radiation and 

chemotherapy after radical hysterectomy: a clinical-pathologic analysis of a 

Gynecologic Oncology Group/Southwest Oncology Group/Radiation Therapy 

Oncology Group trial. Gynecol Oncol. 2005 Mar; 96(3):721-8.5. Delgado 

G, Prospective surgical-pathological study of disease-free interval in patients 

with stage IB squamous cell carcinoma of the cervix: a Gynecologic Oncology 

Group study. Gynecol Oncol 1990; 38:352.6. Sedlis A, A randomized trial 

of pelvic radiation therapy versus no further therapy in selected patients with 

stage IB carcinoma of the cervix after radical hysterectomy and pelvic lymphadenectomy: 

A Gynecologic Oncology Group Study. Gynecol Oncol 1999; 

73:177.7. Rotman M, A phase III randomized trial of postoperative pelvic irradiation 

in Stage IB cervical carcinoma with poor prognostic features: follow-up 

of a gynecologic oncology group study. Int J Radiat Oncol Biol Phys 2006; 

65:169. 

Challenges in dose escalation in head and neck 

radiation oncology 

170 speaker 

CONFORMAL AVOIDANCE OR DOSE PAINTING AS THE NEXT 

STEP FOR INCREASING THE THERAPY 

P. Engström 1 , L. McDermott 2 

1 LUND UNIVERSITY HOSPITAL, Radiation Physics, Lund, Sweden 

2 NETHERLANDS CANCER INSTITUTE, Radiation Oncology Department, 


"For fine strokes you need a thin brush" Dose painting and "theragnostic 

imaging" - whereby dose is planned according to the imaged tumour radioresponsiveness 

in 4D - is counter intuitive for physicists. Painting suggests 

2D, sculpting suggests 3D. Nevertheless, the objective is to prescribe 

dose in much more detail than conventional homogeneous distributions within 

the PTV, using biological imaging. Delineation of the target volume on CT 

scans has long been the bottle neck of radiotherapy uncertainties. With PET, 

SPECT and MRI information, the ability to distinguish between benign and


malignant cells has become vastly improved. The use of specific imaging 

markers for hypoxia and cell proliferation brings even more information to the 

palette of the dose painter. While the benefits are clear, there are obvious 

reasons for caution - such as redistribution of dose within the tumour, the 

clinical validity of biological labels on images and the temporal stability of indicators 

(e.g. oxygenation). And these are reasonable clinical arguments. A 

consideration for the physicist is that all this dose painting detail is superfluous, 

and even potentially harmful, if the level of accuracy cannot be matched 

by both geometrical and dosimetric accuracy. Two things can go wrong between 

planning and treatment: the dose can go to the wrong place and the 

wrong dose can be delivered. If a 5% boost is prescribed to a malignant region 

of 3 mm extent within the GTV, you need to be sure that the patient’s 

positioning (including physiological organ movement) is much better than 3 

mm and dose verification is much better than 5%. Both 3D in-room imaging 

and 2D (or preferably 3D) in vivo dosimetry currently exist that can provide 

this level of accuracy. Cone-beam CT and EPID dosimetry can make such 

levels of accuracy possible and on a large scale too. However, without such 

tools, dose painting efforts make for very nice art work, but do not work as 

science. 

171 speaker 

NORMAL TISSUE DOSE-VOLUME CONSTRAINTS IN THE OPTI- 

MIZATION PROCESS (E.G. SWALLOWING MUSCLE, PAROTID, 

LARYNX) 

A. Eisbruch 1 


The first step in the optimization process for IMRT of head and neck (HN) 

cancer requires the clinical identification of which are the important structures 

whose function we would like to spare. After these structures are defined, we 

can then try to correlate dose and function in order to know what are the 

compromises which are worthwhile taking regarding target doses, in order 

to maximize the probability of complication-free local/regional tumor control. 

The clinical process leading to the identification of the important structures 

has not been straightforward. The initial structures which we have tried to 

spare were the parotid glands, assuming that 1. their sparing will eliminate 

xerostomia, and, importantly, 2. it was relatively easy to spare contralateral 

glands. The initial hypothesis was that we will be able to find partial gland volumes 

receiving certain doses which will be consistent with preserved function. 

Our results revealed several thresholds of partial volumes and doses, 

however, they were all highly correlated with each other, as well as the mean 

dose. The mean dose therefore emerged as the main dosimetric measure. 

The weakness in this measure is that different RT techniques producing different 

dose distributions within the glands are expected to produce different 

relationships between partial volume doses and mean doses, resulting in different 

correlations between mean dose and function. Apart for the dosimetric 

weakness, recent findings by the Groningen group of the differences in doseresponse 

of different anatomical parts of the rat parotid glands highlight the 

potential importance of the spatial dose distribution, about which we do not 

have human data. The next issue emerged after treating patients with parotid 

sparing 3D RT or IMRT and the realization that while xerostomia is reduced, it 

has not been eliminated. This has led to the clinical understanding of the importance 

of the mucin-rich minor salivary glands within the oral cavity and the 

submandibular glands. Establishing dose-response relashionships for these 

glands has therefore become necessary in order to try and spare them while 

minimizing compromises in target doses. A similar clinical process is occurring 

in the efforts to reduce dysphagia, which is arguably the most important 

complication following aggressive chemo-RT of HN cancer. The identification 

of the most important structures whose sparing is likely to result in a clinical 

benefit, establishing dose-response relationships using adequate metrics, 

and understanding the weaknesses and limitations in interpreting such 

results, are essential. These issues will be updated and discussed. 

172 speaker 

EVALUATION AND MANAGEMENT OF LATE SIDE EFFECTS AFTER 

INTENSIFIED HEAD AND NECK RADIOTHERAPY 

J. Kaanders 1 

1 RADBOUD UNIVERSITY NIJMEGEN MEDICAL CENTRE, Dept. of Radiation 

Oncology, Nijmegen, Netherlands 

Intensified radiotherapy regimens are being employed in head and neck cancer 

to increase tumor control and maintain organ anatomy. Strategies include 

altered fractionation, dose escalation by high precision radiotherapy 

techniques and combination of radiotherapy with chemotherapy or biological 

response modifiers. However, organ preservation does not necessarily 

translate to the preservation of function. Although the organ may remain 

anatomically intact, late radiation damage at the tissue level and to related 

structures can significantly impair organ function. Many functions and in particular 

speech and swallowing are complex processes involving the interaction 

of a large number of cranial nerves, muscles and mucosal structures 

requiring precise coordination. A thorough understanding of the pathophysi- 

S 57 

ology of late radiation side effects is therefore essential for devising effective 

preventative and rehabilitation strategies. Intensified treatments are accompanied 

by increased acute and often also late morbidity although the latter 

is less well documented and often underestimated. Clinical trials advocating 

organ preservation and function sparing tend to focus on tumor control 

and early toxicity. Few studies provide detailed and objective assessments 

of long-term functional outcome and late morbidity. This requires standardized 

and prospective surveillance programs. Limited history and physical examination 

suffice as baseline screening but patients presenting with noticeable 

impairments require evaluation by a multidisciplinary team of medics and 

paramedics and specific function tests. First and foremost is the prevention 

of late adverse effects. Highly conformal radiotherapy techniques such as 

IMRT and adaptive radiotherapy offer great prospect. Further optimization of 

these high precision radiotherapy techniques requires the identification of the 

various structures associated with the risk on a given side effect and detailed 

dose-volume characteristics. This is an important field of ongoing research. 

Next in the management of late morbidity is early recognition and timely initiation 

of rehabilitative and supportive care programs. Finally, research into 

strategies for relieving the burden of late effects is crucial to improve the quality 

of life of long-term survivors of head and neck cancer. 

Advanced Treatment Planning in brachytherapy 

173 speaker 

DOES CTV-TO-PTV MARGINS MAKE SENSE IN BT 

K. Tanderup 1 


Denmark 

CTV-to-PTV margin is a concept originating from external beam radiotherapy 

(EBRT). The margin ensures that geometric uncertainties during fractionated 

radiotherapy will not lead to significant underdosage of the target. 

Geometric uncertainties in EBRT are caused by system (accelerator, couch 

etc) and set up uncertainties, and organ/target movement. A margin is therefore 

added to the CTV in order to increase the size of the prescription dose 

plateau. The same kind of errors is present in brachytherapy although of 

different size. System uncertainties are mainly due to small uncertainties in 

source positioning (


the reconstruction process could lead to geometrical uncertainties and thus 

uncertainties in definition of source positions. When using rigid applicators 

(e.g. ring applicator) it is most accurate to use pre-defined applicator geometry 

(library applicator) which is imported into the acquired 3D study. The 

applicators will appear as black areas in a T2 MR image when MRI is used 

in combination with rigid plastic applicators. A library applicator should then 

preferably include the outer dimensions of the applicator, while the treatment 

planning system should facilitate rotation and translation of the applicator until 

it fits the MR study. If the applicator reconstruction is directly performed using 

transversal CT images, a marker-string is often used to define the source 

or dwell positions. The string will not be visible on MR or US images. For 

MRI, plastic tubes filled with water, oil or gadolinium could be used. The 

inner diameter of the inserted plastic tube (i.e. the volume of the contrast 

medium) has a lower limit in order for the marker-string to be visualised. It is 

important to minimise any displacement of the applicator in relation to adjacent 

structures during the time between the image acquisition and the treatment. 

In transrectal US-based treatment planning for high dose rate prostate 

brachytherapy the treatment should be performed with the patient in lithotomy 

position. When treating several fractions using the same implant, the position 

of the applicators in relation to the target volume and organs at risk should be 

evaluated prior to each fraction. 

175 speaker 

INVERSE DOSE PLANNING IN IMAGE BASED BT, PROSPECTS 

AND PITFALLS 

C. Kirisits 1 

1 MEDICAL UNIVERSITY OF VIENNA, Department of Radiotherapy, Vienna, 

Austria 

Inverse planning is no standard procedure for most brachytherapy treatments. 

However, already more than 10 years ago a fast simulated annealing algorithm 

to optimize permanent prostate seed distributions was presented. The 

two major research groups (mainly based in Quebec/San Francisco, and Offenbach, 

Germany) focused first on solutions for prostate brachytherapy. In 

literature their algorithms are know as Inverse Planning with fast Simulated 

Annealing (IPSA) and Hybrid Inverse Planning Optimization (HIPO), respectively. 

In the meantime both have been included into commercial treatment 

planning systems. Major vendors for brachytherapy planning systems are developing 

inverse planning tools. Several studies, including publications from 

independent groups, demonstrated the feasibility and advantages of inverse 

planning for prostate brachytherapy (HDR and seeds). Dedicated class solutions 

improve the reproducibility, decrease the effect of learning curves and 

accelerate the planning process. In addition inverse planning allows achieving 

complex dose distributions in case of multiple targets or boosting structures.The 

essential part of all these developments was that manual planning 

of several hundred patients led to the establishment of general treatment 

planning rules. This was initially missing when transferring the good experience 

from prostate to GYN implants. While interstitial techniques seem to be 

comparable to prostate, intracavitary or intracavitary/interstitial combinations 

needed further adaptation of the initially developed algorithms. Especially the 

unique spatial distribution of high dose regions in cervix cancer brachytherapy 

has to be taken into account. Prostate treatment plans, including dose 

and volume constraints for target, urethra, rectum, and bladder are different 

to GYN cases. Besides these organs, the sigmoid, but also non contoured 

structures as vagina, connective tissue, ureter, nerves and vessels in the 

parametrium have to be taken into consideration. A pure dose point or DVH 

based concept is not sufficient for such cases, and additional anatomy based 

loading and modulation restriction is needed. The experience for other sites, 

including breast, is very limited at the moment and needs further analysis and 

adaptations. For all sites, it seems mandatory to first investigate not only dose 

or volumes parameters for inverse plans, but also to study the whole loading 

pattern and dose distribution based on clinical experience with forward planning. 

Mechanisms and treatment of normal tissue damage 

176 speaker 

PREDICTION OF WOUND HEALING RESPONSE IN THE RT PATIENT 

M. McKay 1 

1 PETER MACCALLUM CANCER INSTITUTE, East Melbourne, Australia 


177 speaker 

RADIATION-INDUCED HEART DISEASE: POSSIBLE THERAPEUTIC 

INTERVENTIONS 

M. Boerma 1 , J. Wang 2 , A. Kulkarni 2 , K. Roberto 1 , M. Hauer-Jensen 3 

1 UAMS, Pharmaceutical Sciences, Little Rock, USA 

2 UAMS, Surgery, Little Rock, USA 

3 UAMS, Department of Surgery and Pathology, Little Rock, USA 

Radiation-induced heart disease (RIHD) is a potentially life-threatening side 

effect of radiation therapy of thoracic and chest wall tumors whenever all or 

part of the heart is included in the radiation field. Manifestations of RIHD 

include acute and chronic pericarditis, accelerated atherosclerosis, myocardial 

fibrosis and valve abnormalities. Chronic manifestations of RIHD become 

apparent ten years after radiation therapy. Especially in patients treated before 

the 1980’s, a 2-fold increase in cardiovascular mortality is seen after 

radiation therapy for breast cancer and Hodgkin’s disease. Despite current 

advances in radiation delivery and treatment planning, cardiac radiation exposure 

still cannot be fully prevented in many cases of thoracic radiation 

therapy. Indeed, studies show myocardial perfusion defects in a large proportion 

of patients within months after irradiation. Although the long-term 

significance of these perfusion defects remains to be determined, they may 

suggest ischemic changes in the heart after thoracic radiation therapy. There 

is currently no method to prevent or reverse RIHD. Therefore, research is urgently 

needed to unravel the mechanisms of RIHD and develop intervention 

strategies. Experimental models have helped elucidate some of the mechanisms 

of cardiac injury after localized heart irradiation. A prominent clinical 

manifestation of RIHD is myocardial fibrosis. Although some symptoms of 

RIHD, such as intimal thickening of coronary arteries, are less pronounced 

in heart of rats and rabbits than in humans, both animal models are excellent 

for studying radiation-induced myocardial fibrosis. Experimental studies 

have shown that microvascular damage contributes to the pathophysiology 

of RIHD. Several studies have also shown a role for transforming growth factor 

beta in the formation of myocardial fibrosis. We have performed studies 

to address the potential roles of mast cells and endothelin in the heart after 

irradiation. Experimental in vivo models have been used to test potential 

intervention strategies in RIHD. Studies have shown that radiation-induced 

myocardial fibrosis is reduced in animals treated with angiotensin converting 

enzyme inhibitors, or with amifostine. Recently, we have shown that a 

combination of pentoxifylline and vitamin E reduced myocardial fibrosis and 

improved left ventricular function when administered after local heart irradiation 

in rats. Although the above studies have shed some light on potential 

interventions in RIHD, more research is needed to reduce the incidence and 

severity of this radiation therapy side effect in our growing population of longterm 

cancer survivors. 

178 speaker 

LONG-TERM FIBROGENIC SIGNALS IN RADIATION-INDUCED 

TISSUE REPAIR 

M. C. Vozenin-Brotons 1 , H. Haydont 1 

1 IRSN/IGR, UPRES EA 27-10, Villejuif, France 

Fibrosis is a common side-effect of cancer treatment by radiotherapy, which 

affects long-term cancer survivor quality of life and will become a serious 

clinical issue within the next years. Activation of TGF-b1 was recognized as a 

central mediator involved in the initiation of radiation fibrosis via activation of 

the Smad3/4 signaling pathway (1) and subsequent transactivation of alphasmooth 

muscle actin and extracellular matrix (ECM) genes (2). However, 

based on our studies performed on human samples of radiation enteropathy 

(RE) presenting with long-term established fibrosis, we questioned the role 

of the TGF-b1/Smad3/4 pathway in the maintenance of the fibrotic process 

(3,4). In long-term established fibrosis like that associated with delayed RE, 

in situ TGF b1 deposition is low, whereas CTGF expression is high. To explore 

this apparent paradox, cell response to increasing dose of TGF b1 was 

investigated in cells modeling initiation and maintenance of fibrosis i.e. normal 

and fibrosis-derived smooth muscle cells respectively. Activation of cell 

specific signaling pathways, by low TGF b1 doses, was demonstrated with a 

main activation of the Rho/ROCK pathway in fibrosis-derived cells, whereas 

the Smad pathway was mainly activated in normal cells. This leads to subsequent 

and cell-specific regulation of the CTGF gene, suggesting a specific 

pro-fibrotic role for CTGF in fibrosis-initiated cells. Thereby, the modulation of 

CTGF expression by itself and the combination of TGF b1 and CTGF was investigated 

in fibrosis-derived cells. CTGF auto-induction was shown and low 

concentration of TGF b1 nenhanced this auto-induction. This study defines 

a novel Rho/ROCK, Smad3 independent mode of TGF b signaling that may 

operate during the chronic stages of fibrosis and provides evidence of both 

specific and combinatorial roles of low TGF b1 dose and CTGF (5). These results 

re-enforce this idea that targeting the Rho/ROCK signals is an efficient 

anti-fibrotic treatment as recently shown in pre-clinical experiments (6). 1. 

Flanders, K. C et al. (2002) Am J Pathol 160(3), 1057-1068; 2.Verrecchia, F 

et al. (2001) J Biol Chem 276(20), 17058-17062; 3.Vozenin-Brotons, MC. et 

al. (2003) International journal of radiation oncology, biology, physics 56(2), 

561-572; 4. Haydont, V. et al. (2005) Radiother Oncol 76(2), 219-225; 5.


Haydont, V. et al. (2008 in press) Am J Physiol, Cell physiol; 6. Haydont, V. 

et al. (2007) Clin Cancer Res 13(18 Pt 1), 5331-5340 

Protons/heavy ions/BNCT 

179 speaker 

EVIDENCE FOR ION THERAPY 

J. Debus 1 

1 UNIV. KLINIKUM HEIDELBERG, Heidelberg, Germany 


180 speaker 

FUTURE CHALLENGES IN HADRON THERAPY 

A. Lomax 1 

1 PAUL SCHERRER INSTITUTE, Villigen - PSI, Switzerland 


181 speaker 

PROMISES AND CLINICAL ACHIEVEMENTS OF BNCT: THE 

FINNISH EXPERIENCE 

H. Joensuu 1 

1 HELSINKI UNIVERSITY CENTRAL HOSPITAL, Oncology, Helsinki, Finland 

Purpose: Boron neutron capture therapy (BNCT) is based on the nuclear 

capture reaction that occurs when non-radioactive boron (10B) is irradiated 

with neutrons of thermal energy to yield high energy alpha particles (4He2+) 

and recoiling lithium (7Li) nuclei. The effect of α and 7Li is primarily limited to 

boron containing cells, since they have pathlengths of approximately one cell 

diameter in tissue. The success of BNCT is dependent upon a selective uptake 

of sufficient amounts of 10B into cancer cells as compared with normal 

tissues. We have evaluated BNCT using boronophenylalanine (BPA) as the 

boron carrier in the treatment of glioblastoma and inoperable head and neck 

cancer that has recurred locally following surgery and conventional photon 

irradiation. 

Methods: 121 patients diagnosed with glioblastoma or head and neck cancer 

were treated at the Helsinki University Central Hospital/VTT BNCT facility 

by February 2008. The first completed clinical trial involved 12 patients with 

locally recurred, inoperable head and neck cancer (rT3, rT4, or rN2). The 

study participants had received a cumulative dose of 54 to 74 Gy conventional 

photon irradiation at the time of primary surgery. Two BPA-based BNCT 

treatments, administered 34 to 83 days apart, were given to treat recurrent 

cancer. 

Results: Ten (83%) of the patients responded to BNCT with a median response 

duration of 12.1 months. Three of the 12 subjects survived for 2 

years without cancer recurrence, and one patient is currently alive without 

recurrence 3 years after treatment initiation. Due to frequent responses observed 

the protocol was subsequently expanded to 30 patients, of whom 29 

were entered by February 2008. In addition, 21 patients with recurred, inoperable 

and irradiated head and neck cancer have now been treated with 

BNCT outside of the clinical trial for various reasons. Early efficacy results 

from these cohorts are in line with the first series. 

Conclusions: Most patients with inoperable, locally recurred head and neck 

cancer respond to BNCT despite having been treated with prior conventional 

radiotherapy or chemoradiotherapy. Few patients may become long-term survivors. 

The results will be updated at the meeting. Future protocols are being 

considered to evaluate BNCT administered concomitantly with chemotherapy 

or with targeted agents. 

Modern dose calculation methods in radiation oncology 

182 speaker 

MONTE CARLO TREATMENT PLANNING FOR RADIATION THER- 

APY 

J. M. Fernández-Varea 1 

1 UNIVERSITAT DE BARCELONA, Facultat de Fisica, Barcelona, Spain 

Monte Carlo (MC) methods have become powerful tools to describe the transport 

of radiation through matter. The two most remarkable advantages of 

S 59 

these techniques are the possibility of incorporating accurate radiation interaction 

properties (cross sections) and the flexibility to deal with complex geometries. 

This had led to the widespread use of MC codes in medical physics, 

in particular to calculate absorbed dose distributions for treatment planning 

in radiation therapy. In the presentation, a brief overview will be given of 

the cross-section databases adopted by the most popular general-purpose 

MC codes, together with the implemented geometry packages. Algorithms to 

speed up the tracking of charged particles will be summarized. Considerable 

reduction in the simulation times can be achieved by MC codes specialized 

for radiotherapy-type applications, whose underlying simplifications shall be 

outlined. Finally, we will focus on important issues related to MC treatment 

planning. These include the generation of phase-space files and beam modelling, 

specific variance-reduction techniques, denoising of dose distributions, 

and the conversion of MC dose information into absorbed dose to water. 

183 speaker 

ADVANCED KERNEL METHODS VERSUS MONTE CARLO BASED 

DOSE CALCULATIONS FOR HIGH ENERGY PHOTON BEAMS 

D. Georg 1 , P. Winkler 1 


Austria 

Purpose: Monte Carlo dose calculation algorithms are becoming commercially 

available for high energy photon beams. On the other hand, accurate 

advanced kernel based methods are in clinical use for many years. The aim 

of this study was to compare the accuracy of both types of dose calculation 

in simulated clinical settings. 

Methods and materials: The treatment planning systems investigated were 

Oncentra Masterplan (Nulcetron, V3.0) with a collapsed cone (CC) convolution 

algorithm, iPlan (BrainLAB, V4.0) and Monaco (CMS, V1.0). The latter 

two TPS offer XVMC based Monte Carlo (MC) dose calculation. All systems 

were commissioned for an ELEKTA Synergy platform providing 6, 10 and 

18MV beams. Measurements were performed with a calibrated ionization 

chamber in a reference point and radiochromic EBT type films. In a first step, 

single field geometries were verified in a homogenous polystyrene phantom 

in order to exclude large commissioning errors. Second, standard and IMRT 

treatments were delivered to an inhomogeneous phantom where cork was 

used to simulate lung. Dose calculation was carried out with a calculation 

grid size of 2x2x2mm. Dosimetric comparisons included single points, and 

1D as well as 2D gamma evaluations using 2mm and 2% dose difference 

criteria. Finally, dose calculation speed was assessed in the light of future 

demands for on-line treatment planning. 

Results: Ionization chamber measurements in the isocenter revealed no 

large differences between MC and CC dose calculation. For line profiles 

and depth dose curves (various field sizes) the mean gamma values were 

0.46±0.17 (6MV), 0.43±0.16 (10MV), and 0.44±0.20 (18MV) for the CC algorithm 

and 0.42±0.14, 0.44±0.12, and 0.43±0.15 for the MC systems. The 

number of points exceeding the gamma criteria was between 9% and 13% for 

all systems. Measurements in the presence of heterogeneities revealed no 

significant differences between CC and MC dose calculations. Time for dose 

calculation was about 1min per field for the CC algorithm and up to 10 times 

higher for the MC systems, depending on field size. 

Conclusion: The dosimetric difference between advanced kernel methods 

and Monte Carlo based dose calculation was small and comparable to the 

measurement uncertainty. The current project will be extended to additional 

treatment planning systems with advanced kernel methods, i.e. ADAC Pinnacle 

with a collapsed cone convolution algorithm and Varian Eclipse with an 

analytical anisotropic algorithm (AAA). 

184 speaker 

MODERN ALGORITHMS FOR DOSE CALCULATIONS IN 

BRACHYTHERAPY 

A. Meigooni 1 

1 UNIV. OF KENTUCKY MEDICAL CENTER, Lexington, USA 

The significance of brachytherapy treatment in treatment of various cancer 

sites has been demonstrated by various investigators around the globe. Traditionally, 

this treatment modality was performed only by limited institutions. 

However, the wide spread of this treatment technique can be attributed to the 

advancement of the source design, improvement of treatment delivery technique, 

and development of the treatment planning systems based on the most 

recent algorithms provided by the AAPM (American Association of Physicist 

in Medicine) Task Group 43 (TG-43). The formalism introduced by this protocol 

is as follows:


Where D(r,θ) is the dose rate at point P(r,θ), SK is the air kerma strength, Λ 

is the dose rate constant, GL(r,θ) is the geometric function, gL(r) is the radial 

dose function, and F(r,θ) is the 2D anisotropy function. This algorithm and the 

corresponding parameters had been verified and improved by different investigators 

using experimental and theoretical techniques within past decayed 

couple of decayed. This formalism is easy to adapt for any treatment planning 

systems and the parameters in this protocol are relatively easy to determine. 

In addition, it has been demonstrated that the various independent investigators 

were able to obtain the dosimetric parameters of one source type with a 

good agreement with the others. Although, the initial phase of this protocol 

was mainly for the interstitial brachytherapy sources, different investigators 

had shown its application for other source types such as intravascular beta 

and photon emitter sources, high energy photon emitter sources. 

The original TG-43 formalism was created in polar coordinate system. However, 

Schaart et al. 1 that the dose distribution around intravascular line 

sources, can be better described using a similar formalism in cylindrical coordinate 

system. At our institution, we have recently verified that with cylindrical 

coordinate system one could achieve the dose distribution around both small 

(active length ≤ 1cm) or elongated source (active length > 1cm) 2 . The application 

of the original and updated TG-43 formalism as modern algorithms 

for dose calculation around the brachytherapy sources will be reviewed. Also, 

the possible routes for the future work will be presented. 

1. Schaart DR, Clarijs MC, Bos AJ. On the applicability of the AAPM TG- 

60/TG-43 dose calculation formalism to intravascular line sources: proposal 

for an adapted formalism. Med Phys. 2001;28(4):638653. 

2. Awan SB, Dini SA, Hussain M, Soleimani-Meigooni DN, and Meigooni 

AS, Cylindrical coordinate-based TG-43U1 parameters for dose calculation 

around elongated brachytherapy sources. JOURNAL OF APPLIED CLINI- 

CAL MEDICAL PHYSICS, VOLUME 9, NUMBER 2, SPRING 2008 

Management of upper GI tumors 

185 speaker 

RADIOLOGICAL IMAGING OF THE UPPER GI TRACT, THE STOM- 

ACH 

L. Grenacher 1 

1 UNIVERSITY OF HEIDELBERG, Department of Diagnostic and Interventional 

Radiology, Heidelberg, Germany 

By means of ongoing developments and increasingly sophisticated endoscopic 

techniques, the value of radiologic diagnostic methods in the upper 

GI-tract has undergone considerable changes. Conventional barium meal 

studies have eventually lost their predominant role in the diagnostic workup 

of the upper GI-tract except for the immediate postoperative controls. 

Endoscopy is considered the gold standard for primary evaluation and diagnosis. 

Beside endoscopy, endosonography is distinctly helpful as a complementary 

technique, due to its high spatial resolution to evaluate inflammatory 

changes, and the depth of tumor infiltration in small carcinomas and 

carcinomas associated with ulcerations. 

Despite the high sensitivity of conventional radiography with a detection rate 

of carcinomas between 85 to 90%, this modality has lost its value in the preoperative 

diagnostic management of diseases of the stomach due to the increasing 

availability of endoscopy and the value of cross sectional imaging. 

As a result of these competitive diagnostic modalities, the number of conventional 

radiologic investigations is decreasing and the optimal expertise of the 

trainee radiologist is difficult to maintain and to be guaranteed. 

Double contrast techniques have continuously been demoted to a historical 

diagnostic tool. 

CT, and Multi-Detector-Row Computed Tomography (MDCT, Multislice-CT 

=MSCT) in particular, plays a very important role in staging malignant tumors 

of the stomach. The distinctly optimized technique of so called "Hydro-CT" 

including distension to the gastric wall with 1-1.5 l oral contrast media, mainly 

water, has fostered the diagnostic value of CT in the diagnosis of diseases of 

the stomach. Under using these "Hydro-CT" technique the detection rate of 

gastric carcinoma is between 89% up to 94% and for liver metastasis between 

85% to 92% because of its outstanding possibilities to delineate infiltrations 

of neighboured vessels or organic structures. For the overall T staging the 

sensitivity is rather low between 43% to 65%, for the lymph nodes between 

64 to 88%. 

According to the tumor type MSCT supplies first morphological details to define 

the entity of the lesion (polyps, gastritis, lymphoma, GIST, carcinoma). 

Nevertheless the definite differential diagnosis remains difficult. In addition, 

multiplanar reconstruction (MPR) derived from MD-CT data sets, are very 

helpful to localize these pathologies and to demonstrate their anatomic relationship 

to adjacent organs and vascular structures. 

Actually, MRI plays no major part in the diagnostic evaluation of the upper GItract. 

Staging and extension of local infiltrations can be done by CT equally. 

Complementary or facultative use is possible.Images:Image 1: Hydro-CT of 

a GIST tumorImage 2: Hydro-MRI of a GIST tumorImage 3: Hydro-CT with 

coronal MPR of a gastric lymphomaImage 4: Hydro-MRI of a gastric carcinoma 

186 speaker 

POSTOPERATIVE CHEMORADIOTHERAPY IN GASTRIC CANCER- 

FROM PHASE I TO PHASE III STUDIES 

E. Jansen 1 

1 NETHERLANDS CANCER INSTITUTE, Radiotherapy, Amsterdam, Nether- 

lands 

Surgical resection remains the cornerstone of curative treatment of gastric 

cancer. However, with surgery only, long-term survival is poor, especially 

in patients with T3-4 tumors and/or tumor positive lymph nodes. Randomized 

studies that compared standard limited (D1) lymph node dissections 

with more extended (D2) resections in the Western world, failed to show a 

significant survival benefit for more extensive surgery. Other studies failed to 

show a benefit of postoperative radiotherapy or chemotherapy when applied 

as single treatment. A substantial increase in survival was found with perioperative 

chemotherapy with epirubicin, cisplatin and 5-FU in the so called 

MAGIC study (1). In addition, the SWOG/Intergroup 0116 study showed that 

postoperative chemoradiotherapy with 5-FU prolonged 5 year overall survival 

compared to surgery only (2). At the Netherlands Cancer Institute phase 

I-II studies with daily or weekly adjuvant cisplatin and capecitabine based 

chemoradiotherapy have been performed in over 120 patients with resected 

gastric cancer. These studies demonstrated that intensive postoperative concurrent 

chemoradiotherapy is feasible. Furthermore effort was put in optimizing 

radiotherapy technique. With 3D- or IMRT techniques it is possible to 

adequately irradiate a postoperative CTV, while sparing kidneys and liver. In 

addition, CTV delineation guidelines have been developed aiming at minimizing 

inter- and intraobserver variability. For daily practice it remains unclear 

whether patients with operable gastric cancer should have pre- (and post-) 

operative chemotherapy or postoperative chemoradiotherapy. To resolve this 

dilemma the CRITICS study was developed, a joint effort between surgeons, 

gastroenterologists, medical oncologists, pathologists and radiation oncologists 

in the Netherlands (and currently Sweden). The CRITICS study is a randomized 

phase III trial (clinicaltrials.gov NCT 00407186) in which all patients 

receive 3 courses of ECC (epirubicin, cisplatin, capecitabine) chemotherapy 

and then have a D1+ gastric resection. After surgery patients receive either 

another 3 courses of ECC chemotherapy or chemoradiotherapy (45 Gy in 

25 fractions, with weekly cisplatin and daily capecitabine). Endpoints of this 

study are overall and disease-free survival, toxicity and quality of life. Furthermore, 

tissue banking and analysis (genomics, proteomics) are part of the 

study. Quality assurance both in radiotherapy and surgery (Maruyama index) 

is obligatory. At the meeting the following topics will be addressed: studies 

that led to the development of the CRITICS study and characteristics of 

modern gastric cancer radiotherapy. References: 1. Cunningham D et al. N

TUESDAY, SEPTEMBER 16, 2008 YOUNG SCIENTIST SESSION 

Engl J Med 2006; 355: 11-20 2. Macdonald JS et al. N Engl J Med 2001; 

345:725-30 

187 speaker 

SMALL CELL CARCINOMA OF THE OESOPHAGUS 

E. Hudson 1 , J. Powell 1 , S. Mukherjee 1 , D. Crosby 1 , E. Brewster 1 , S. 

Maughan 1 , H. Bailey 1 , F. Lester 1 

1 VELINDRE NHS TRUST, Cardiff, Wales, United Kingdom 

Primary small cell oesophageal carcinoma (SCOC) is rare, prognosis is poor 

and metastases are often present at the time of diagnosis. Due to its rarity, an 

optimum treatment strategy has not been established. Small cell lung cancer 

(SCLC) is a far more common disease, and shares many clinicopathologic 

features with SCOC. Therefore, a similar staging and treatment strategy for 

SCOC was adopted. We report our clinical experience using this strategy, 

and review the published literature on SCOC. All cases of SCOC referred 

to Velindre Hospital, UK, between 1998 and 2005 were identified. Survival 

was recorded from the date of histological diagnosis. Staging was analogous 

to that used in SCLC; limited disease (LD) was defined as a tumor 

mass contained within the oesophagus or perioesophageal tissues, such that 

the disease can be encompassed within a tolerable radiation therapy port, 

and extensive disease (ED) included all other patients. Survival was calculated 

using the Kaplan-Meier method. For the literature review, the electronic 

databases MEDLINE, EMBASE and Cancerlit were searched. Sixteen patients 

were identified. Age range was 48-81 years with a median age of 68.5 

years and 12/16 (75%) patients were female. In all cases, pure SCOC was 

reported. In total, 13/16 patients had disease in the lower 1/3rd and 3/16 had 

disease in the middle 1/3rd. In total, 6/16 (38%) patients had LD, and 9/16 

(56%) had ED. Stage was not recorded in 1/16 (6%) patient. Chemotherapy 

was given to 6/9 patients with ED; all received four to six cycles of PE 

(carboplatin AUC 5-6 i.v. plus oral etoposide 3-weekly). Chemotherapy was 

given to 5/6 patients with LD. One patient received six cycles of ICE. The others 

received four to six cycles of either PE or CE (cisplatin 60-80mg/m2 i.v 

and oral etoposide 3-weekly). All five patients received RT to the oesophagus 

given with curative intent following a PR to chemotherapy. Two patients 

also received PCI. RT to the oesophagus was given 3-4 weeks after the last 

cycle of chemotherapy. Doses varied between 30-50Gy in 12-25 fractions 

over 2-5 weeks. The median survival of all 16 patients was 13.2 months 

(95% CI 7.7-18.7). The median survival of patients with ED and LD was 

9.1 months (95%CI 3.3-14.8) and 24.4 months (95%CI 19.9-28.9) respectively. 

No prospective randomized trials were identified, and caution should 

be applied when basing treatment strategies on retrospective data, as poor 

record keeping and bias may influence results. However, for localised disease 

platinum-based combination chemotherapy and RT to the oesophagus may 

provide effective local control and avoid the morbidity of extensive surgery. 

Oesophagectomy or RT alone are probably inadequate, and if used, should 

be combined with adjuvant or neoadjuvant platinum-based chemotherapy. 

The role of PCI is controversial, and should be discussed with patients on 

an individual basis. For those patients presenting with metastases, palliative 

chemotherapy may prolong survival. 


Evidence Based Medicine 

188 speaker 

S 61 

EVIDENCE BASED MEDICINE: FRACTIONATION, STEREOTACTIC 

IRRADIATION AND PARTICLE BEAM RADIOTHERAPY 

B. A. Jereczek-Fossa 1 

1 UNIVERSITY OF MILAN&EUROPEAN INSTITUTE OF ONCOLOGY, Radiation 

Oncology, Milan, Italy 

Fractionation. Based on the empiric background, 1.8-2Gy daily doses are 

routinely used in RT. Altered fractionation has been tested for many years in 

order to improve treatment efficacy and/or reduce normal tissue injury. The 

most studied tumor sites include head&neck, breast and prostate malignancies. 

Recently, the results of large studies and meta-analyses have been published. 

MARCH meta-analysis showed that altered fractionated RT improves 

survival in patients with head&neck cancer. Comparison of the different types 

of altered RT suggests that hyperfractionation has the greatest benefit. Two 

large START studies on breast cancer demonstrated that hypofractionation 

delivering 40Gy/15 fr. or 41.6Gy/13 fr. was associated with the rates of localregional 

tumour relapse and late adverse effects at least as effective as the 

standard schedule of 50Gy/25 fr. This finding is consistent with the hypothesis 

that breast cancer and the dose-limiting normal tissues respond similarly to 

change in fraction size. Several pilot studies on the prostate cancer showed 

the feasibility of hypofractionation, however the results of ongoing randomized 

trials are awaited before this approach become routine in prostate cancer. 

Stereotactic radiotherapy (SRT). SRT is a novel technique that takes 

advantage of the technologic improvement in dose delivery and verification. 

Randomized data showed that SRT boost after whole brain RT (WBRT) improves 

survival in selected patients with single brain metastases. Although 

the addition of SRT to WBRT improves local control in patients with up to four 

metastases, it does not affect overall survival in patients with multiple metastases. 

Phase I/II trials for tumors of the lung, liver, spine, pancreas, kidney, 

and prostate demonstrated that SRT may provide results similar to surgery, 

while avoiding morbidities associated with that invasive approach. Phase III 

trials are warranted to firmly establish the role of SRT. Particle beam. Particle 

beam RT can represent several radiobiological and physical advantages over 

conventional photon RT: improved dose distribution, permitting dose escalation 

within the target and optimal sparing of normal tissues. Preclinical and 

clinical studies suggest a potential gain in the tumors characterized by poor 

radiosensitivity and critical location. The most used hadrons are at present 

protons and, still on the experimental basis, carbon ions. Some indications for 

proton RT for ocular melanoma and skull base tumors (chordoma and chondrosarcoma) 

are accepted by the radiation oncology community. Pilot studies 

on the carbon ion RT of skull base tumors, head and neck tumors, nonsmallcell, 

lung cancer, hepatocellular carcinomas, bone and soft-tissue sarcomas, 

and prostate showed promising results, however well designed prospective 

clinical studies are sorely warranted in order to establish the role of this RT 

modality in cancer care. 

189 speaker 

EVIDENCE BASED MEDICINE- COMBINATION DRUG TREATMENTS 

IN RADIATION ONCOLOGY 

R. Simcock 1 

1 BRIGHTON AND SUSSEX UNIVERSITY HOSPITALS NHS TRUST, Sussex 

Cancer Centre, Brighton, United Kingdom 

The combination of radiotherapy with drug treatments offers potential for 

improved treatment results through non-interactive and interactive mechanisms. 

Developments in drug therapy have offered new cytotoxic agents, 

novel schedules and targeted molecular therapies for investigation. These 

developments have occurred alongside advances in supportive care that have 

allowed for safer management of acute toxicities. Chemoradiation using platinum 

-based chemotherapy regimens is a long established practice however 

published evidence (Level 1a to Level 3) on ideal schedule, dose and combination 

treatment continues to accumulate. Regimens containing platinum and 

taxanes are being investigated as both induction (neoadjuvant) and concomitant 

strategies attempting to maximise spatial cooperation and independent 

cell kill. A universally accepted standard of care has not been defined.Hypoxic 

cell sensitisers with chemoradiotherapy continue to be tested for their potential 

for radiation enhancement and Level 2 evidence is available. EGFR inhibitors 

used with radiotherapy can improve local control. Mechanisms for 

this effect include increased cell kill, radiosensitisation and inhibition of DNA 

repair. Relatively low toxicity profiles encourage combination with other treatments 

to maximise therapeutic ratio. Novel therapy strategies have now been 

tested in randomised controlled trials in head & neck and Level 2 evidence 

is now accumulating in other disease sites. Potential advantages and problems 

with these drug combination strategies will be explored and new data 

will be reviewed and presented according to treatment strategy and level of 

evidence.


190 speaker 

EVIDENCE BASED MEDICINE-NEW TECHNOLOGY IN RADIATION 

ONCOLOGY 

D. Zips 1 

1 UNIVERSITY HOSPITAL, TU DRESDEN, Radiation Oncology, OncoRay 

Radiation Research Center, Dresden, Germany 

Development and availability of new technology is a major driving force in 

the progress of radiation oncology. Conceptually new technologies strive for 

widening the therapeutic window of radiotherapy which is defined by the separation 

of the radiation dose effect curves of local tumour control and normal 

tissue complication probabilities. This can be achieved for example by increased 

conformality and precision of beam delivery, by consideration spatial 

heterogeneity of radiation resistance within tumours and by assessment of 

temporal changes in anatomy and physiology for adaptive treatment. Examples 

for advanced technology applications in radiation oncology are intensitymodulation, 

image guidance, 4D-treatment planning and adaptive treatment 

delivery. Recent evidence arising from planning studies, prospective clinical 

applications as well as of controlled clinical trials using new technology will 

be reviewed. 

Symposium 

Definitive treatment in cervix and endometrium 

cancer: new horizon 

191 speaker 

IMAGE GUIDED ADAPTIVE RADIOTHERAPY FOR CERVIX CANCER 

- GYN GEC ESTRO RECOMMENDATIONS 

R. Pötter 1 


Austria 

Image guided radiotherapy for cervix cancer has been recently introduced as 

a specific approach for individualized and focused brachytherapy. The major 

tool has been MRI at diagnosis and after 4-5 weeks of radio-chemotherapy 

- at the time of brachytherapy with the MRI compatible applicator in place. 

There is major anatomical change during this interval in advanced disease 

mainly due to tumour remission which requires adaptive 4 D treatment planning. 

Visualisation of the applicator is provided together with (residual) tumour, 

cervix, uterine corpus, parametria, vagina and adjacent organs at risk. 

The applicator is reconstructed onto the MR images to enable the accurate 

definition of source dwell positions and times. Concepts and terms were developed 

for a systematic MRI based approach for tumour and target assessment 

(Gyn GEC ESTRO Recommendations I RadiothOncol 2005, 74:235). 

Based on contouring of GTV, CTV and OAR, treatment planning is performed 

aiming at adaptation of the appropriate dose to the CTV and at meeting certain 

dose volume constraints for OAR. Specific dose volume parameters were 

introduced: D 90, D 100 for CTV, 0.1 ccm, 1 ccm, 2 ccm for OAR (GEC ES- 

TRO Rec. II RadiothOncol 2006, 78:67). Doses are normalized to 2 Gy per 

fraction (EQD2) by applying the linear quadratic model and are summarized 

for dose constraints (IJROBP 2007, 69:619). This systematic approach has 

been successfully implemented clinically mainly by European centres. Dose 

volume adaptation for target and OAR was proven to be clinically feasible 

(e.g. IJROBP 2005, 62:901). Through a dedicated network (Gyn GEC ES- 

TRO) specific issues of this complex procedure have been addressed with 

regard to training and education as well as to research and development. 

Up to 4/2008 about 500 patients have been treated applying this MRI based 

adaptive approach. First clinical results as published in a large series of 141 

patients from Vienna (RadiothOncol 2007, 83:148) and reported from other 

centres during recent meetings (Paris, Leuven, Aarhus (~150 patients)) indicate 

local control rates approaching 100% for limited disease and extensive 

good responding disease and about 90% for extensive disease with poor response 

by applying total doses >87 Gy EQD2 (HRCTV). The rate of late 

adverse side effects seem to be low (G3,4 5500 patients) established 

a hazard ratio of 0.73 when chemotherapy is used. Similar benefit 

accrued for non-platinum containing chemotherapy including 5FU and Mitomycin. 

In certain settings 5FU (oral or intravenous) could replace cisplatin. 

The absolute benefit of CT/RT is 10%, 7% and 3% in Stage I/IIA, IIB and IIIB 

respectively. Of the failures 52% are locoregional and 44% are distant. The 

challenge for future trials is to improve both locoregional control and distant 

metastases. Hypothesis generating data from this analysis suggests that adjuvant 

chemotherapy may add incremental benefit; this has not been tested in 

clinical trials. Novel targeted therapies, e.g. antiangiogenics, antiviral agents, 

monoclonal antibodies or tyrosine kinase inhibitors need to be investigated. 

In the GOG study recurrent, persistent and metastatic disease in no significant 

outcome differences, were observed between four platinum doublets. 

Progression-free survivals (PFS)are < 6 months. Various risk factors shorten 

PFS including performance status > 0, pelvic disease, prior use of concurrent 

platinum, and < 1 year to recurrence. Standard antineoplastics are of little 

utility. Current trial proposals include the addition of Bevacizumab to conventional 

antineoplastics. Future progress in cervical cancer rests in making 

vaccine prevention accessible world-wide.


193 speaker 

LOCAL CONTROL AND SURVIVAL IN DEFINITIVE RADIOTHERAPY 

OF ENDOMETRIUM CANCER: ROL 

C. Haie-Meder 1 , I. Dumas 2 , T. Messaï 1 , C. Lhommé 3 

1 INSTITUT GUSTAVE-ROUSSY, Radiotherapy, Villejuif, France 

2 INSTITUT GUSTAVE-ROUSSY, Physics, Villejuif, France 

3 INSTITUT GUSTAVE-ROUSSY, Medical Oncology, Villejuif, France 

The standard treatment of endometrial cancer consists of total hystectomy 

and bilateral salpingo-oophorectomy +/- pelvic +/- paraaortic lymph node dissection. 

Severe comorbidities may lead to preclude surgery. In this situation, 

definitive radiotherapy, including brachytherapy, represents the only curative 

option. CT and more accurately MRI images provide information for GTV (and 

more particularly tumour thickness), CTV and organs at risk assessment, 

complementary to clinical examination. CTV for external irradiation includes 

the whole uterus, the paracolpic and parametrial tissues, the upper vagina 

and iliac lymph nodes. PTV is usually defined as the CTV plus a 1cm margin 

in all directions. At the time of brachytherapy, CT and/or MRI compatible 

applicators allow a more precise definition of the target volume and a better 

assessment of the dose delivered to the critical organs. The GTV includes 

the primary tumour and its local extension. Although no clear recommendation 

has been reported, CTV for brachytherapy includes the GTV plus the 

whole uterus, and the upper third of the vagina. Different types of applicators 

have been described in the literature, some of them being standardized 

(modified Heyman packing, Rotte applicator, multiple-channel Bauer applicator), 

the others being more individualized (umbrella technique). Treatment 

plannings for brachytherapy are not standardized even if some specification 

points have been described (point My or "serosa" point or A-line). Nowadays, 

a more sophisticated approach includes optimization with dwell time and location 

adaptation. The total dose depends on the therapeutic approach using 

brachytherapy alone or combined with external irradiation. The brachytherapy 

dose also depends on the dose-rate. For brachytherapy alone, a total 

dose of 60 Gy to 75 Gy is delivered with LDR or PDR, while 5 to 6 fractions 

of 7 Gy are delivered with HDR, some authors using a BID schedule. When 

combined with external irradiation, either the number of fractions or the dose 

per fraction is reduced. External irradiation dose ranges from 30 Gy to 45 

Gy, depending on tumour extension and/or lymph node involvement. Results 

using the 3-D approach with DVH analysis are rather scarce. For external 

irradiation, IMRT seems to reduce the absolute rectal wall, bowel and bladder 

volumes at the prescribed dose with the bladder filling being an important cofactor 

of IMRT benefit. DVH analysis is also in favour of the supine position 

for definitive radiotherapy to anticipate a rectal protection for brachytherapy. 

For brachytherapy, DVH analysis evidences the difficulty to include the whole 

uterus to the prescribed dose without reaching the maximal tolerable doses 

to critical organs. Further studies are necessary to better define the dose 

necessary to the CTV, while the GTV requiring the maximal dose should be 

defined as accurately as possible with all the modern image tools available. 

What is the standard of care for unresected locally 

advanced HNSCC? 

194 speaker 

INDUCTION AND/OR CONCOMITANT CHEMOTHERAPY? 

L. Licitra 1 

1 ISTITUTO NAZIONALE DEI TUMORI, Milan, Italy 


195 speaker 

LARYNX PRESERVATION: A SUCCESSFUL MULTIMODALITY 

APPROACH? 

J. L. Lefebvre 1 

1 CENTRE OSCAR LAMBRET, Head and Neck, Lille, France 

For a long period of time either radical surgery (total laryngectomy, TL) or 

defintive radiotherapy (RT) were proposed for the treament of previously untreated 

advanced larynx/hypopharynx squamous cell carcinoma. Treatment 

choice was only based on institutional policies. There was no consensus on 

a randomized comparison between both approaches, that should have been 

the first larynx preservation (LP) trial. In the early 80s, cisplatin + 5FU (PF) 

appeared as able to provide in previously untreated patients impressive response 

rates and to predict radiosensitivity of responding tumours. On this 

basis a multidisciplinary discussion could at last lead the first generation of 

LP trials based on induction chemotherapy (ICT). Patients eligible for a TL 

were randomized between the conventional treatment (LT +/- postop RT) and 

the experimental treatment (ICT followed by RT in good responders or by 

LT +/- postop RT in poor responders). From the published randomized trials 

S 63 

(VA, EORTC 24891, GETTEC) it appeared that survival was not inferior in 

the experimental arm (except in the GETTEC trial) and that nearly 60 % of 

larynx could be preserved. As that time concurrent chemoradiotherapy (CT- 

RT) appeared as superior to ICT in terms of locoregional control and survival 

(MACH-NC). The second generation of LP trials compared ICT followed by 

RT in good responders with CT-RT (and in one trial, RTOG 91-11, with RT in 

a third arm). It appeared that CR-RT was able to provide higher LP rates (up 

to 84 %) but again without any impact on survival and at the price of a higher 

acute and late toxicity that could compromize the function of the preserved 

larynx. The EORTC 24954 comparing ICT versus alternating CT-RT failed 

to find any difference between both arms. Meanwhile docetaxel + PF (TPF) 

ICT appeared to improve both locoregional control and overall survival as 

well as the concurrent administration of RT and cetuximab, a molecular targeted 

therapy blocking the EGFR pathway, in randomized trials. Of interest 

the acute toxicity was not increased in either approach. In a subset analysis 

of larynx/hypopharynx SCC in two randomized trials, LP appeared to be 

higher with TPF or with RT + cetuximab. Finally a randomized trial comparing 

PF versus TPF followed by RT in good responders showed an higher LP 

but no advantage in survival in the TPF arm. A fair multidisciplinary collaboration 

has allowed finetuning the treatment of advanced larynx/hypopharynx 

SCC (LT or various LP strategies). The current multidisciplinary discussion 

is aiming to assess in LP approches the respective role of TPF-ICT versus 

CT-RT, the feasibility of ICT followed by CT-RT, how to integrate cetuximab 

in this clinical reseach, how to improve survival and how to better assess LP 

as a part of the overall outcome. Future research should also pay attention 

to biological and/or imaging tools able to select patients to various strategies 

and to monitor the treatment and the follow-up. 

196 speaker 

RADIOTHERAPY AND A TARGETED AGENT WITH OR WITHOUT 

CHEMOTHERAPY? 

B. O’Sullivan 1 

1 PRINCESS MARGARET HOPSITAL, UNIVERSITY OF TORONTO, Radiation 

Oncology, Toronto, Canada 

Evidence from randomized trials and meta-analyses have established the 

place of intensified approaches using chemotherapy with radiotherapy (RT) 

or altered fractionation RT to achieve dual goals of organ preservation and 

cure of unresected locally advanced head and neck HNSCC. At the same 

time emerging awareness exists that these goals are being attained at the 

price of functional debilitation for a proportion of these patients. A recent tendency 

has included the design of trials that apply even greater intensification 

as newer approaches emerge from the efficacy results of other trials. Some 

contemporary trials are including combinations of several approaches, with 

great emphasis on cancer control and potentially less attention to the consequences 

for patient morbidity and function. For multiple reasons, that include 

costs, monitoring, and availability of instruments needed to perform reliable 

late effects morbidity evaluation, many trial strategies have not been able to 

focus reliably on long term treatment sequelae assessment. Most recently, 

targeted agents have emerged as part of the treatment armamentarium led 

by the EGFR inhibitor class of agents in combination with RT. While such 

agents are associated with unique problems, they also open the therapeutic 

door to the possibility of achieving similar tumor control to those expected 

with more conventional approaches, but with a different and potentially more 

acceptable toxicity profile. This presentation will focus on the potential for the 

development of trials that address "chemo-sparing" strategies that could substitute 

the use of an EGFR antibody in place of concurrent high dose cisplatin 

combined with 70 Gy of fractionated RT, seemingly the world wide standard. 

The use of "chemo-additive" approaches that include targeted approaches in 

combination with chemo-RT are also being evaluated and will also be discussed. 

However our group would contend that an important question that 

patients need answered at this time is whether we can achieve comparable 

control rates with less toxicity than other widely used strategies. The potential 

for combination of RT with EGFR blockade to achieve this are real. 

Answers to such a question would have practice changing potential because 

of its focus on the therapeutic index. Trials addressing such questions are 

complex due to non-inferiority design concerns, the choice of control group in 

the present changing therapeutic environment for head and neck cancer, and 

the need for assessments that address patient quality of life and functional 

outcome. Ideally such evaluation should also include attention to swallowing 

assessment and economic analysis and tissue acquisition for potential molecular 

correlates with outcome. Unless the medical community takes some time 

to consider strategies and goals that are relevant to patient utility in locally 

advanced HNSCC trial we will simply continue a burdensome journey of enhancing 

survival at any cost. Unfortunately, in the end our patients are the 

ones who will bear this burden.


Volume effects in image guided brachytherapy 

197 speaker 

RELATING CLINICAL DATA TO DVH PARAMETERS IN GYNE BT 

J. Dimopoulos 1 

1 MUV, Radiotherapy, Vienna, Austria 

In 3(4)D image guided brachytherapy (IGBT) of cervical cancer systematic 

integration of concepts for DVH-parameters with cautious dose volume adaptation 

are associated with high local tumour control rates (~85%) and low 

rates of late side effects (


Beam Quality: To deliver a high dose, the constraint is always to maintain 

an acceptable dose to healthy tissues. So multiplying the gantry angles drive 

to a quantity close to conventional treatments. However, concerning geometry, 

an isocenter, a gantry angle or a collimation have to be secured with a 

lower tolerance value. Dosimetric aspects like homogeneity, linearity or reproducibility 

have also to be the subject of a particular QA program. 

Dosimetric validations: An important dosimetric validation work has to support 

the clinical aspects. Anthropomorphic phantoms and adapted dosimetry 

detectors have to be used to simulate treatments and prove that all the procedure 

respects the quality level and the expected prescription. 

Conclusion: To deliver a high dose in one session will never be a simple 

event. One has to keep in mind that any error will be irreparable. All dosimetric 

parameters get an increased importance. Before thinking about the 

radiobiology and positioning aspects, the ability to guaranty a coherent beam 

quality is dominating. Many departments are ready now to go on such protocols. 

It’s time to highlight the need of acquiring adapted competence before 

the first treatment. 

All you need to know about Hadron therapy 

203 speaker 

NEW CONCEPTS IN ACCELERATOR AND DELIVERY SYSTEMS 

FOR PARTICLE THERAPY 

M. Schippers 1 

1 PSI, Accelerator department, Villigen, Switzerland 

The strong increase of interest in radiation therapy with protons or carbon 

ions at clinics in Europe, Asia and the USA has encouraged new developments 

and a large product choice from various vendors. During the past 

most beam delivery techniques have been developed in accelerator laboratories, 

but at present a breakthrough is observed as these techniques have 

been further developed by industry and are becoming applicable for routine 

use in clinical environments. However, new techniques are coming up and in 

order to maintain the advantages of particle therapy, it is the task of industry 

to incorporate these into their products. The accelerator used for particle 

therapy is a cyclotron or a synchrotron. For economic reasons a particle therapy 

facility consists of several treatment rooms, alternately supplied with the 

beam from one common accelerator. To spread the dose over the tumor, 

different beam delivery techniques can be used and applied with a gantry. 

The technique that has become standard practice for protons is based on 

a "scattered beam". More recently the "spot scanning" technique (currently 

only in use at PSI, Switzerland, and GSI, Germany) is being implemented at 

several new facilities. There are two lines of new developments. First of all 

there are projects aiming for improvement of the current techniques (e.g. fast 

3D pencil beam scanning at PSI), in order to obtain the ultimate reachable 

accuracy with protons or ions and to cope with moving targets or organs at 

risk. Secondly several groups are investigating alternative accelerator techniques. 

The reduction of size and improvement of beam quality are typical 

goals in the development of new accelerators for carbon ions. For protons, 

one aims at (cheap) integrated accelerator+gantry systems, applicable at single, 

stand alone, relatively small treatment rooms. When choosing a beam 

delivery technique, it should be noted that this choice also has consequences 

for the particle accelerator (cyclotron or synchrotron), as well as the type of 

gantry. Depending on the goals of a future hadron therapy facility, one has 

to consider above consequences in relation to costs, available space and 

future upgrades. In order to judge new developments, one has not only to 

consider their (usually claimed economic) advantages, but above all whether 

they can at least provide treatments with the same quality as the current particle 

therapy modalities. Different techniques, accelerators and proposals will 

be reviewed. 

204 speaker 

ABSOLUTE AND RELATIVE DOSIMETRY FOR PROTON THERAPY 

H. Palmans 1 

1 NATIONAL PHYSICAL LABORATORY, Radiation dosimetry, Teddington, 


Radiotherapy using proton beams has been a steadily growing modality for 

several decades but has seen a new and substantial growth in recent years. 

Commercial installations for pure therapeutic use based on conventional accelerators 

such as cyclotrons and synchrotrons are now available and the 

prospect of new and cheaper beam production techniques such as laser acceleration, 

non-scaling fixed field alternating gradient synchrotrons and dielectric 

wall accelerators will further increase interest in proton therapy. Despite 

these developments, dosimetry for proton beams has not reached the 

same level of accuracy and consistency as for x-rays, thus compromising its 

full potential exploitation. An overview and current status of techniques used 

for absolute and relative dosimetry will be given. For absolute dosimetry, 

calorimeters are the first choice since they provide the most direct measurement 

of absorbed dose to water, the quantity of interest. Water and graphite 

S 65 

calorimeters are most commonly used and the National Physical Laboratory 

is at present building a primary standard level graphite calorimeter. Absolute 

dosimetry can also be based on fluence measurements using Faraday cups 

or activation measurements, especially for scanned pencil beams, but with 

more difficulty to reach the desired accuracy. Advantages and difficulties of 

each of these methods will be discussed. Ionisation chambers are the most 

widely used instruments for reference dosimetry in the clinic. While they could 

in principle also be used to derive absorbed dose to water from first principles, 

their practical use relies on calibrations that are at present only available 

in photon beams. This results in complications related to differences in 

interaction data between protons and photons and potentially significant perturbations. 

Recent activities to review, revise and improve these data will be 

presented. Several problems encountered in relative dosimetry for protons 

have a lot in common with those in photon beams in particular where small 

fields, adjacent fields and sharp gradients are involved. One of the main differences 

and concerns in this respect is the dependence on linear energy 

transfer (LET) of the dose response of many detectors in proton beams. For 

ionisation chambers and some types of diodes this proves to be a minor problem 

but for several other detectors suitable for 3D-dosimetry in x-ray beams 

this LET-dependence is substantial. Examples and further discussion will be 

given. 

205 speaker 

ANALYTICAL AND MONTE CARLO DOSE CALCULATIONS FOR 

PARTICLE THERAPY 

H. Szymanowski 1 

1 GERMAN CANCER RESEARCH CENTER, DKFZ, Heidelberg, Germany 

The main requirement of a dose calculation algorithm is the ability to predict 

accurately the dose deposition pattern in the patient within a reasonable 

time, accounting for the physical properties of the treatment beam and for the 

patient’s anatomical data.The most accurate dose calculation method is currently 

provided by Monte Carlo codes allowing the simulation of the particle 

interactions and energy deposit in the tissue at a microscopic scale. Dose calculation 

engines using Monte Carlo simulation codes may however be time 

consuming in comparison to fast analytical dose calculation methods, e.g. 

pencil beam algorithms, which are mostly based on macroscopic modelling 

of particle beam interaction. Basic principles, current developments, advantages 

and limitations of both types of dose calculation algorithms, Monte 

Carlo and analytical, will be reviewed in this lecture. In particular methods 

for the determination of the physical and biological dose from particle 

beams, procedures for the implementation of the physical input data characterizing 

the therapy beam, i.e. the initial phase space of the particles, into 

the dose calculation algorithms and procedures allowing to account for the 

patient anatomical structures and tissue inhomogeneities using information 

from CT data will be presented and discussed. 

206 speaker 

MONITORING OF HADRON THERAPY BY MEANS OF PET TECH- 

NIQUES 

W. Enghardt 1 

1 TECHNISCHE UNIVERSITÄT DRESDEN, OncoRay - Radiation Research in 

Oncology, Dresden, Germany 

According to their favourable physical and radiobiological properties beams 

of protons and ions offer a considerable potential for a precise and highly tumour 

conformal radiation therapy. However, the dose distributions delivered 

by these beams are sensitive to the ion range in-vivo. Therefore, an in-situ 

monitoring of the dose delivery in particular the ion range is desirable. At 

present the only available technology for this purpose is positron emission tomography 

(PET). If a dedicated PET scanner is integrated into the treatment 

site, the technology is called in-beam PET. It is based upon the registration of 

annihilation events following the decay of positron emitters, which are generated 

via nuclear interaction between the impinging ions and the atomic nuclei 

of the tissue irradiated. At the experimental 12 C ion therapy facility at the 

Gesellschaft fr Schwerionenforschung (GSI) in Darmstadt, Germany an inbeam 

PET scanner has been installed and the technique has been clinically 

applied for the first time. At this facility about 400 patients, predominantly with 

radiation resistant tumours in delicate anatomical positions in the head and 

neck region, have been treated since 1997. All treatments have been monitored 

by means of in-beam PET. According to this experience the clinical 

potential of in-beam PET can be evaluated. In-beam PET allows for a beam 

delivery independent verification of the whole chain from treatment planning 

(in particular the physical models) to the dose deposition. Furthermore, it has 

been proven as a valuable tool for detecting and quantifying of randomly occurring 

deviations between the planned and the actually deposited dose distributions. 

The reasons for such deviations are minor patient mispositioning 

or anatomical (i.e. density) modifications of the tissue penetrated by the therapeutic 

ion beams. This information is obtained for each daily dose fraction, 

which offers the possibility of an intervention during the following fractions.


Targeted radionuclide therapies 

207 speaker 

DOSIMETRY METHODS IN SYSTEMIC RADIATION THERAPY 

S. E. Strand 1 

1 MEDICAL RADIATION PHYSICS, Department of Clinical Sciences, Lund, 

Sweden 

Disseminated cancer will have good possibilities of being treated with targeted 

radionuclide therapy (TRT). As radionuclide therapy treatments (RNT) 

are expanding and very high activities are administered, the safety and the 

treatment optimization must be based on proper dosimetry models. No good 

correlation between traditional dosimetry calculations and biological therapy 

effects has been obtained so far. Used semi-quantitative measurements do 

not account for anatomical and physiological variations and can cause either 

inadequate treatment of tumours or excessive absorbed doses to sensitive 

non-target organs resulting in poor therapeutic ratios. Present dosimetry 

therefore needs to be replaced by better 2D and 3D quantification methods 

and more realistic geometrical considerations on the tissue and cellular 

level and where voxel-based dosimetry needs to have a substructure 

in each macroscopic voxel. The pharmacokinetics in vivo of i.e. radioimmunoconjugates 

needs to be guided in order to achieve better therapeutic 

ratios. A future important direction is the combination of nuclear medicine 

techniques SPECT/PET with CT/MRI techniques. Especially the combination 

of PET/SPECT and MRI in one instrumentation is a novel initiative that 

will bring MRI with high spatial resolution and excellent soft-tissue contrast 

for anatomical imaging (however with low sensitivity for quantitative physiological 

imaging) together with PET/SPECT, providing quantitative in vivo information 

about functional processes. To enhance the therapeutic ratio the 

pharmacokinetics needs to be manipulated to reduce the normal tissue exposure. 

Based on quantitative imaging, new treatment strategies will be possible 

to develop for individual patient treatment. Many of these ideas have 

to be tested pre-clinically with high resolution imaging as µ-PET/ µ-SPECT 

supplemented with information on tissue and cellular level combined with histology. 

208 speaker 

RADIOBIOLOGY OF SYSTEMIC RADIOTHERAPY 

D. Murray 1 

1 CROSS CANCER INST., Experimental Oncology, Edmonton, Canada 

Radiobiological modeling of systemic radiotherapy (SRT) has largely depended 

on extrapolation of data obtained using homogeneous exposures to 

single or fractionated doses of radiation delivered at high dose rate (HDR). 

The underlying assumption is that such exposures have biological equivalence 

to the declining low dose rate (LDR) exposures typically administered 

in SRT. In recent years, it has become apparent that the cellular and molecular 

mechanisms by which mammalian cells respond to low dose and/or LDR 

radiation exposures can be quite different from those occurring at HDR. Many 

of these low dose/LDR findings were controversial on their initial appearance, 

often because such effects were not universal. Understanding the mechanisms 

of these various effects will enable us to move forward to the point 

where we will be able to better use this information to guide translational and 

clinical advances. Rooted in this mechanistic discussion is the role of the cellular 

DNA damage surveillance-response network, especially with regards to 

the response to DNA double strand breaks which are the "signature" lesion 

generated by ionizing radiations. Of major importance in this regard are the 

phenomena of low dose hyper-radiosensitivity-increased radioresistance, inverse 

dose-rate effects, adaptive responses, and the bystander effect (which 

is quite distinct from the "crossfire" effect which is also operative in SRT). 

Each of these areas requires a major reconsideration of existing models for 

radiation action and an understanding of how this knowledge will integrate 

into the evolution of clinical SRT practice. Validation of a role in vivo for any 

or all of these effects in SRT would greatly impact the way we would assess 

therapeutic response to SRT, the design of clinical trials of novel SRT radiopharmaceuticals, 

and risk estimates for both therapeutic and diagnostic radiopharmaceuticals. 

Also of great interest is the radiation-dose responsiveness 

and LDR implications of the various modes of cell death, such as apoptosis 

and accelerated senescence. The current state of research in LDR effects 

therefore offers a major opportunity to critically address the basic science of 

clinical SRT practice, to use this new knowledge to expand the use and roles 

of SRT, and to facilitate the introduction of new radiopharmaceuticals. 

209 speaker 

RECENT DEVELOPMENTS AND FUTURE POSSIBILITIES 

M. Luster 1 

1 UNIVERSITÄT WÜRZBURG, Würzburg, Germany 

Over the last two decades novel treatment modalities, such as radio la- 

beled antibodies and peptides, targeting specific antigens or receptors and 

to a lesser extent local application of radiopharmaceuticals have been introduced 

in the clinical practice. Recently combined approaches using nuclear 

medicine tools in conjunction with chemotherapy, external beam radiation 

therapy and other treatment modalities are more extensively explored.Peptide 

receptor radionuclide therapy (PRRT) consists in the systemic administration 

of a synthetic analogue, radio labelled with a suitable beta-emitting radionuclide. 

These compounds are able to irradiate tumours and their metastases 

via the internalization through a specific receptor subtype, generally 

over-expressed on the cell membrane. PRRT can deliver radiation doses 

to tumours, which are adequate to achieve significant volume reduction. 

Pre-clinical studies have indicated many potential receptor candidates for 

PRRT. To date, the mostly exploited system is the somatostatin-somatostatin 

receptor. Treatment with radio labeled somatostatin analogues, such as 

[ 90 Y-DOTA 0 ,Tyr 3 ]-octreotide and [ 177 Lu-DOTA 0 ,Tyr 3 ]-octreotate, is a promising 

new tool in the management of patients with inoperable or metastasized 

gastro-entero-pancreatic (GEP) neuroendocrine tumours. Clinical trials performed 

in several countries, despite different phase I-II protocols, thus not 

specifically addressing efficacy, showed complete and partial responses in 

10 to 30% of patients for [ 90 Y-DOTA 0 ,Tyr 3 ]-octreotide. In the clinical trial with 

[ 177 Lu-DOTA 0 ,Tyr 3 ]-octreotate, 47% overall response rate was observed, with 

a median time to progression of >36 months. Significant biochemical and 

symptomatic responses in functioning tumours were encountered for both 

radiopeptides. Toxicity, requiring renal-protective agents, is generally mild 

and may involve kidneys and bone marrow. These data indicate that PRRT 

is a convincing alternative in the treatment scenario of GEP tumours.Newer 

peptides, with higher affinity for other somatostatin receptor subtypes, are 

presently under investigation and could extend PRRT to other endocrine 

as well as non-endocrine tumours.Following the same targeting principle, in 

the future, PRRT could be addressed to tumours such as breast, prostate, 

pancreas, and brain cancer, whose cells over-express receptors for several 

neuropeptides such as bombesin, gastrin, neurotensin, substance P, GLP-1, 

neuropeptide Y, and CRH. In this respect, clinical experiences are ongoing 

with radiopeptides including radiolabelled gastrin analogues in medullary thyroid 

carcinoma, substance-P analogues in high-grade glioma and bombesin 

analogues in hormone-refractory prostate carcinoma.Two radio labeled anti- 

CD20 monoclonal antibodies are currently available for radioimmunotherapy 

(RIT) of B-cell lymphoma, i.e. Y-90-ibritumomab tiuxetan(Zevalin_, IDEC 

Pharmaceuticals and Schering AG, Berlin, Germany) and I-131-tositumomab 

(Bexxar_, Glaxo Smith Kline, Philadelphia PA). Beta-emitting radionuclides 

(i.e. Y-90, I-131, Cu-67, Lu-177) are mostly used for B-cell lymphomas in clinical 

trials. For the treatment of microscopic disease and leukaemia, these radionuclides 

do have the disadvantage that their beta energy results in energy 

deposition beyond the targeted cell. Another option is the useof targeted alpha 

particles with radionuclides such as bismuth-213 or actinium-225, which 

offers both the possibility of selective tumour cell kill with less damage to 

surrounding normal cells and a higher radiobiological effectiveness. In a 

series of clinical trials patients achieved excellent overall response rates of 

50 -80%, with complete response rates of 20 - 40%.The introduction of radio 

labeled mIBG enabled successful imaging of neuroectodermally derived 

tumours (neuroblastomas, pheochromocytomas, paragangliomas, medullary 

thyroid carcinomas, carcinoid tumors) and has led to the development of I-131 

mIBG treatment of those malignancies. This therapy leads to symptomatic 

and hormonal improvement and moderate tumour regression/stabilization in 

patients with metastatic disease with an acceptable rate of adverse effects. 

Bone-seeking radiopharmaceuticals are one of the therapeutic tools available 

for palliation of bone pain and should be used within a multidisciplinary 

approach, in order to choose the best option for each patient in a correct 

sequence. Intravenous injection of Sr-89 chloride, Sm-153 lexidronam or 

186 Re-etidronate is used for the treatment of bone pain due to osteoblastic 

metastases or mixed osteoblastic lesions from prostate or breast carcinomas 

(established indications) or any other tumour presenting osteoblastic lesions 

seen as areas of intense uptake at bone scan. Clinical practice and experimental 

studies demonstrated that treatment can be safely performed after 

local field external beam radiotherapy. The onset of response is rapid after 

treatment with short-lived isotopes (i.e. Sm-153 lexidronam and Re-186 

etidronate). After treatment with long-lived isotopes (Sr-89), the onset is prolonged 

for a few weeks. The duration of response, on the other hand, is 

longer for long-lived radioisotopes than for short-lived isotopes.Local application 

of radiopharmaceuticals in liver tumours has become widely accepted 

mainly due to its favourable toxicity profile and the feasibility of combination 

with other therapies such as systemic chemotherapy and limited liver resection. 

Management of lower GI tumors 

210 speaker 

A SYSTEMATIC OVERVIEW OF RADIATION THERAPY EFFECTS IN 

RECTAL CANCER 

P. Maingon 1 

1 CENTRE GEORGES-FRANÇOIS LECLERC, Radiotherapy, Dijon, France


Although the rate of local recurrence after multimodality treatment for primary 

rectal cancer has decreased considerably since the introduction of total 

mesorectum excision, up to 1/3 of patients develop a locoregional relapse 

during the course of their disease. According to the long-term results of 3 recent 

randomized trials, preoperative radiotherapy + 5 FU provides improved 

tumor down-staging and local control. However no significant difference has 

been achieved yet in a 5 year disease free and overall survival rates. All 

patients received 55 Gy preoperatively, which is considered as a standard 

therapy in the EORTC. The 5 x 5 Gy preoperative irradiation with immediate 

surgery has gained much popularity in Europe. The high effectiveness 

and low toxicity of this scheme of fractionation have been demonstrated in 

Swedish and Dutch randomized trials. Furthermore it is not clear whether 

chemoradiation offers an advantage in sphincter preservation in comparison 

with 5 x 5 Gy schedule. Refinement of the radiotherapy technique and a 

more accurate selection of patients suitable for the treatment probably further 

improve the results at least in regard to treatment related complication. 

High resolution magnetic resonance imaging has achieved good accuracy 

in the preoperative prediction of positive circumferential radial margin, death 

of extra-mural spread and other poor prognostic features suggestive of locally 

advanced disease. The impact of pathologic downstaging and local recurrence 

and positive circumferential resection margin (CRM) on local recurrence 

and survival in patients treated with neoadjuvant chemo-radiotherapy is 

one of the most important prognostic factors in terms of risk of subsequent local 

recurrence and disease free survival rate. The CRM should be considered 

a major prognostic factor and should be validated in further trials as an early 

alternative clinical endpoint. Morphological features and molecular markers 

majoring the effects of preoperative radio-chemotherapy are expected to correlate 

with downstaging and seems to be an important factor for response. 

An emerging strategy to improve outcome is to incorporate new biologically 

active, target therapy to establish combined chemoradiation regimens in the 

preoperative setting. With the aim to improve local control and reducing systemic 

micro-metastasis, the use of neoadjuvant combination chemotherapy 

seems to be interesting to study as induction before radiotherapy of before 

combined modality treatment. Obviously, well-defined clinical target volume, 

limited to the mesorectum should be promoted to improve acute tolerance 

and anorectal functions after these neoadjuvant strategies. 

211 speaker 

THE TME TRIAL: WHAT HAVE WE LEARNED IN 10 YEARS? 

C. Marijnen 1 

1 THE NETHERLANDS CANCER INSTITUTE, Clinical Oncology, Amsterdam, 

Netherlands 

Local recurrence is a major problem in rectal cancer treatment. Preoperative 

short term radiotherapy has shown to improve local control and survival 

in combination with conventional surgery. The Dutch TME trial investigated 

the value of this regimen in combination with total mesorectal excision (TME). 

Long term results are reported after a median follow-up of 6 years. Five year 

local recurrence risk of patients undergoing a macroscopically complete local 

resection was 5"6% in case of preoperative radiotherapy compared to 10.9% 

in patients undergoing TME alone (P < 0"001). Overall survival at 5 years was 

64"2% and 63"5% respectively (P = 0"902). Subgroup analyses showed significant 

effect of radiotherapy in reducing local recurrence risk for patients with 

nodal involvement, for patients with lesions between 5 and 10 centimetres 

from the anal verge. The results of both the Dutch TME as well as the MRC 

CR07 study demonstrate that for patients with a positive circumferential resection 

margin, the recurrence rate is high after preoperative radiotherapy, but 

also after postoperative (chemo)radiotherapy. These findings suggest that a 

conventional radiotherapy scheme might be a better option. Reliable preoperative 

identification of patients at risk for positive resection margins is therefore 

very important. Apart from the beneficial effects, side-effects of the treatment 

should be taken into account. Several studies have demonstrated that acute 

toxicity after this type of radiotherapy is acceptable. However, more recent 

studies report that fecal incontinence and increased frequency are observed 

more often after preoperative radiotherapy. In addition, sexual dysfunctioning 

is increased. A recent Swedish report demonstrates increased incidence of 

secondary cancers after short-term preoperative radiotherapy. The question 

is therefore whether short-term preoperative radiotherapy is needed for all patients. 

Better patient selection to identify patients at risk for local recurrence 

is therefore necessary. In addition, informing patients about side-effects and 

patient participation in treatment decision making should be advocated. 

212 speaker 

NEW DEVELOPMENTS IN RADIOTHERAPY FOR RECTAL CANCER 

(E.G. CBCT, FUNCTIONAL IMAGING) 

I. Mertens 1 , S. Roels 1 , K. Haustermans 1 

1 UNIVERSITY HOSPITAL LEUVEN, Department of Radiation Oncology, 

Leuven, Belgium 

In locally advanced rectal cancer, the combination of pre-operative 

(chemo)radiotherapy followed by TME-surgery, has reduced the overall local 

S 67 

recurrence rate to less than 10%. However, a significant difference in local 

recurrence rate exists between patients with or without tumoral involvement 

of the circumferential resection margin (positive or negative CRM). Patients 

with a positive CRM have at least a twofold higher risk to relapse in the pelvis. 

This finding supports the importance of tumor shrinkage (downsizing) in patients 

with a narrow or involved CRM at diagnosis. In this high-risk group, a 

supplemental dose to the tumor could induce more downsizing and thereby 

improving local control. When dose-escalation to the tumor is considered, 

new challenges in radiotherapy planning emerge. Due to the relatively small 

tumor volume and the continuous movement of the pelvic organs, the risk to 

partly "miss" the tumor is high. Therefore a real-time tumor tracking system, 

like cone-beam-CT (CBCT), seems to be promising to ensure daily tumor localisation. 

However, even with a CBCT-equipped linear accelerator, correct 

dose-delivery is not obvious. Firstly, the low soft tissue contrast of the CBCT 

images makes the distinction between tumoral tissue and normal rectal wall 

difficult. Therefore, additional rectal contrast or tumor clipping (placement 

of fiducial markers around the tumor) are useful and need to be evaluated. 

Secondly, current treatment planning is only based on pre-treatment imaging. 

Ideally, the treatment should be adapted daily to the actual position and shape 

of the patient and the tumour. However, adaptive RT still poses many technical 

problems, including the use of CBCT for accurate dose calculation and 

treatment dose accumulation and techniques for deformable image registration. 

Until these issues are solved, the variation in position and shape of the 

rectal tumor must be taken into account by applying safety margins around 

the target volume. Recently, MRI and PETCT have been tested to optimize 

tumor definition and delineation in rectal cancer. Repeating these imaging 

modalities during and after radiotherapy can be used for adaptive treatment, 

but also for tumor response prediction. If this prediction is reliable, patients 

can eventually be selected for more or less aggressive treatment, including 

organ sparing surgery.

S 68 YOUNG SCIENTIST SESSION TUESDAY, SEPTEMBER 16, 2008 


Young Poster Session 

213 oral 

SECOND NAL-PROTOCOL CAN IMPROVE THE SETUP FOR LUNG 

PATIENTS TREATED WITH RESPIRATORY GATED RADIOTHERAPY 

B. Haring 1 , J. Cuijpers 1 , J. Van Sörnsen de Koste 1 , F. Spoelstra 1 , S. 

Senan 1 , B. Slotman 1 

1 VU UNIVERSITY MEDICAL CENTER, Radiation Oncology, Amsterdam, 

Netherlands 

Purpose: Patients with stage III lung cancer can benefit from respiratory 

gated radiotherapy treatment (RGRT) that allows smaller radiation fields 

to be used as treatment is restricted to typical moments during breathing. 

Moreover, use of audio-coaching during end-inspiration (EI) period gating 

showed an average of 10.2 % mean increased lung volume compared to 

free-breathing, thereby reducing lung doses (Haasbeek et al, IJROBP-2008). 

However, besides proper target definition, accurate RGRT requires that patient 

setup error is minimal. We present a patient setup correction protocol 

facilitating this requirement. 

Materials: Free breathing 4DCT scanning is routinely performed in lung patients 

undergoing RT treatment. When tumor motion exceeds 7.5 mm or if 

RGRT is expected to reduce lung dose, an audio-coached 4DCT planning 

scan is acquisitioned immediately afterwards. The EI gating window typically 

presents 30% of the breathing cycle. The target is defined by contouring 

tumor in three successive respiratory phase bins around EI period. The reconstructed 

Average Intensity Projection (Ave-IP) data set is used for dose 

calculation and the corresponding Ave-IP DRR is used to verify patient setup 

at the treatment unit. Patient setup during treatment is verified using a No 

Action-level (NAL) patient setup and correction protocol (Boer IJROBP-2005), 

that estimates the mean setup error using the first three fractions and applies 

a correction for the remaining treatment sessions. A second NAL-procedure 

is performed halfway the treatment to correct for possible time-trends. Verification 

during the treatment was performed by acquiring Time-integrated 

electronic portal imaging (TI-EPI) for AP treatment beams, which makes it 

possible to verify patient positioning for every treatment fraction. 

Results: Data of 12 patients was available for this analysis. With use of 

the double NAL-procedure, the treatment accuracy increased. The SD for 

systematic errors (Σ) applying one NAL-procedure are 3.2 mm LR and 2.5 

mm SI as for applying 2nd NAL-procedures the Σ are 2.0 mm LR and 1.6 

mm SI. The random errors (σ) for both procedures in both directions stayed 

approximately 3 mm on average. Three patients were repositioned very well 

(σ T 2.0 mm), as 5 patients showed large setup errors (σ d 3.5 mm). As 

images were only obtained in AP direction, there is no information available 

about vertical errors. 

Conclusions: Application of the second-NAL protocol proved very effective, 

thereby allowing for more accurate RGRT deliveries. 

214 oral 

QUALITY AUDITS IN RADIATION THERAPY 

M. Gackle 1 , M. Goharian 2 , W. MacKillop 3 , P. Dunscombe 2 

1 TOM BAKER CANCER CENTRE, Radiation Oncology, Calgary, Canada 

2 TOM BAKER CANCER CENTRE, Medical Physics, Calgary, Canada 

3 QUEENS UNIVERSITY, Kingston, Canada 

Purpose: Health care providers have an obligation to deliver high quality 

patient treatments. However, particularly in a technologically sophisticated 

multidisciplinary environment such as a Radiation Treatment Program (RTP), 

identifying the relevant dimensions of quality and developing metrics for their 

evaluation is challenging. Several approaches to quality audits have been 

developed for use in a variety of jurisdictions. Our interest in this work was to 

apply three audit protocols to the evaluation of one RTP, that at the Tom Baker 

Cancer Centre (TBCC), and to identify similarities and differences in the audit 

outcomes. In order to carry out this study it was necessary to develop a 

compliance grading system that was applicable to the structural standards 

embodied in the three quality audit protocols. 

Materials: The RTP at the TBCC, which delivers 3,000 courses of radiation 

therapy annually, was evaluated against three structural standards: draft 

Canadian Structural Standards (CSS), American College of Radiation Oncology 

(ACRO) Practice Accreditation Program and the International Atomic 

Energy Agency’s (IAEA) Comprehensive Audits of Radiation Practices. The 

structural, as opposed to process and outcome, standards were identified 

and used in this study. Our grading system consists of five levels of progressive 

compliance: none, minimal, partial, substantial and full compliance. In 

order to achieve full compliance, the highest level, a RTP would need documented 

proof that the quality standard has been addressed, implemented 

and is regularly audited to assess for continual improvement and effectiveness. 

An overall grade was assigned by adding the scores for the individual 

structural standards. 

Results: The results are presented as pie charts with the number of individual 

standards in each quality audit indicated. Each of the three standards had 

different formats and emphases which explains at least some of the variation 

in the final grades. 

Conclusions: A simple progressive grading system has been developed and 

applied with the structural quality standards of three different organizations. 

The grading system is general and easy to use. The results provide a clear 

snapshot of the quality of a RTP. The assessment of the three auditing protocols, 

although different in design and format, yielded similar pictures of the 

quality of the TBCC Clinical RTP. 

215 oral 

SKIN MARKING USING PERMANENT MAKE-UP: 3 YEARS EXPERI- 

ENCE IN CLINICAL USE 

C. Siegrist 1 , P. Schneeberger 1 , C. von Briel 1 , P. Cossmann 1 

1 INSTITUTE FOR RADIOTHERAPY, Hirslanden Klinik, CH 5000 Aarau, 

Switzerland 

Purpose: In radiotherapy stringent necessity exists for skin marking in order 

to achieve precise patient positioning for every treatment session, i.e. it is 

an instrument with high impact on quality assurance. Aim of this study was 

to evaluate whether the permanent make-up method is an approach being 

reasonable everyday. 

Materials: The newly designed dedicated system Symphony Liner (Swiss 

Color Int.) has fixed rate of 90 stitches per minute. With disposable needle 

modules little dots or narrow lines can be tattooed onto the skin under sterile 

conditions. The colours used are on a natural basis, not leading to allergic 

reactions by the patients. For an adequate colour choice the undertone of the 

skin is taken into consideration. After the application the stitching areas are


sealed with liquid plaster. We investigated the patient’s choice (new permanent 

make-up vs. conventional pencil marking approach) within a collective 

of 300 patients with regard to sex, age and treatment area and evaluated the 

reasons for their choices. We also looked at pros and cons of both methods 

as well as possible seasonal changes. 

Results: The system is easy to handle, i.e. after a short introduction it can 

be used in daily routine. Directly after the treatment a slight bleeding followed 

by a weak skin irritation in the "tattoo" region can be seen. These effects 

normally disappear quickly and afterwards the dot’s marking looks similar to 

normal liver spots. 50% of the breast patients and 35% of the thorax patients 

decided to undergo permanent make-up marking. For prostate patients 

approx. 40% have chosen the new method. Patients who underwent the permanent 

make-up method didn’t want to have visible lines on their skin, any 

impairment of personal hygiene or sport activities, i.e. no need to care about 

the marking. Reasons against the new method mentioned by the patients 

are pain, no visible memories of the treatment afterwards desired or cosmetic 

objections. 

Conclusions: Our experiences from a 3 years period indicate that the permanent 

make-up method is a real alternative to the conventional way with 

pencil marking. Reactions by the patients are quite different, depending on 

sex, age and treatment region. Slight but not significant seasonal effects also 

have been observed, indicating there are additional influence factors due to 

the summer like swimming and sunbath activities. Depending on the patient’s 

individual physiology the markings should bleach out within 6 months and 2 

years. 

216 oral 

THE USE OF PIXY PHANTOM IMAGES TO ASSESS RADIOTHER- 

APISTS INTER-OBSERVER VARIABILITY IN IMAGE MATCHING 

PELVIC AND THORACIC EPIS 

A. O’Neill 1 

1 CANCER CENTRE, BELFAST TRUST, Belfast, United Kingdom 

Purpose: In the radiotherapy department at the Northern Ireland regional 

Cancer Centre in Belfast, electronic portal imaging remains the gold standard 

for assessing treatment set-up accuracy and has provided the basis for 

establishing our random and systematic set-up errors. A recent software upgrade 

(Aria Off-Line Review version 7.5.49) saw the introduction of new image 

matching tools. This study attempts to establish the level of observer variability 

between radiotherapists using these tools to match DRRs and EPIs. 

Materials: Using a solid anthropomorphic phantom called ’Pixy’ (Elimpex- 

Medizintechnik), helical CT scans were acquired on a GE Lightspeed RT 

wide-bore scanner using standard radiotherapy protocols (2.5 mm slice thickness). 

Simple 3D plans were generated on Nucletron Oncentra Masterplan, 

including high resolution DRRs. Typical treatment images were acquired for 

each field (based on 3 MUs) with a Varian amorphous silicon aS500 EPID 

on a Varian 2100CD Clinac. A group of 10 radiotherapists experienced in 

anatomy matching and review, have matched the phantom images using 

ARIA Offline Review matching software, and recorded their results. Microsoft 

Excel statistical analysis tools were used to calculate the minimum, maximum, 

mean and standard deviation for each image. 

Results: Five sets (AP+LAT) of pelvic EPIs and five sets of thorax EPIs where 

acquired; 20 images in total. We recorded 200 sets of image match data. 

Analysis of match results indicate that the inter-observer variability between 

10 radiotherapists experienced in image matching is 0.8mm or less when 

expressed as the standard deviation for each image matched. 

Conclusions: This study has enabled the measurement of inter-observer 

variability in a group of 10 radiotherapists with similar experience in bony 

anatomy image matching, using ARIA Off-Line Review matching software. 

The DRRs’ and EPIs acquired using the Pixy phantom will facilitate training 

and allow us to assess the impact of future software upgrades on image 

matching consistency. This study provides supporting evidence for the delegation 

of EPI approval from radiation oncologists to radiotherapists and for 

the development of radiotherapists implementing on-set correction protocols. 

217 oral 

QUALITY IMPROVEMENT FRAMEWORK IN RADIOTHERAPY 

V. Fernandes 1 , A. Ferreira 1 , R. Rodrigues 1 , M. Eiras 2 , A. Escoval 3 

1 

HOSPITAL CUF DESCOBERTAS, Radiotherapy, Lisboa, Portugal 

2 

ESCOLA SUPERIOR DE TECNOLOGIA DA SAÚDE DE LISBOA, Radiotherapy, 

Lisbon, Portugal 

3 

ESCOLA NACIONAL DE SAÚDE PÚBLICA, Health Systems Management, 


Purpose: The result of many improvements and developments in quality 

methods and procedures provides a quality improvement framework; however 

all standards should be reviewed over time to track the process if improvements 

can be made. It is only possible to come about by indicators 

assessment to obtain quantitative data on the quality of care given.A study 

has been undertaken to evaluate the quality in a portuguese radiotherapy 

department to provide a continuous quality improvement. 

S 69 

Materials: Under the coordination of an expert in health system management 

a working group consisting of radiation oncologists and radiation technologists 

has started to monitor the performance and quality levels of 13 indicators 

in a typical portuguese radiotherapy department based on the study published 

by Cionini el al. in 2007.The work is being carried out in three steps; 1) 

a preliminary scientific validation of the quality indicators for the portuguese 

reality; 2) collecting data based on the indicators, and 3) a comparison of the 

data collected from the portuguese radiotherapy department with those from 

the italian hospitals. 

Results: The group of indicators to evaluate the material and human resources, 

namely the workload, use of high energy units, instrumentation 

for dosimetry and quality control, treatment planning with CT and waiting 

times, though difficult to measure the last one, have taken a very good quotation. 

The indicator high energy unit downtime for non-planned maintenance 

showed a value under the compliance 0.7. The quality of clinical records 

gets the score 20 of 24, though the very small number of multidisciplinary approach. 

Treatment planning with CT, number of fields per planned treated volume, 

shaped field and portal verification, indicates treatment techniques are 

sufficiently updated. The quality controls and performance checks of treatment 

machines, the procedures are according to the international guidelines. 

The patient satisfaction represents 95% of compliance. 

Conclusions: This is the preliminary results of the first evaluation and was 

very good in general according to the literature.We need to know the current 

base line, and then continuously measure and monitor the indicators, combined 

with feedback, auditing and public disclosure of the measured data, in 

order that these results increase the opportunities for quality improvement as 

well as to educate others by sharing the results of a national and international 

survey. 

218 oral 

EXPECTED VERSUS MEASURED LUNG VOLUME ON FOUR- 

DIMENSIONAL COMPUTED TOMOGRAPHY USING PRESSURE 

SENSOR-BASED BREATHING PHASE RECONSTRUCTION 

E. Kloen 1 , I. Breton 1 , M. Pranger 1 , F. Ubbels 1 , J. Widder 1 , K. Schilstra 

1 , H. Langendijk 1 , H. P. van der Laan 1 



Purpose: During a study involving four-dimensional (4D) computed tomography 

(CT), it seemed that calculated lung volumes in some cases did not match 

the corresponding breathing phases. Therefore, the purpose of this study was 

to compare lung volumes expected on the basis of breathing curves acquired 

by means of a belly belt-derived pressure signal with lung volumes measured 

upon phase assorted 4D-CT images when pressure sensor-based equipment 

for breathing phase is used. 

Materials: Ten patients underwent 4D-CT scanning for radiotherapy planning 

for lung cancer. During CT, respiration was monitored with a belly belt 

equipped with a pressure sensor (Anzai Medical). Abdominal movement resulted 

in a breathing curve that was used to reconstruct CT data sets of the 

whole breathing cycle at 10% intervals. Relative volumes of the right and left 

lung, determined by delineating the lungs for each phase, were compared to 

the relative volumes expected on the basis of the obtained breathing curve. 

Results: In the majority of breathing phases, expected and measured lung 

volumes matched closely and no significant differences were found. However, 

significant differences were found at 10% and 70% expiration, where 

the mean measured relative lung volumes indicated that the actual phases of 

expiration were 3% (0-12%, p=0.01) and 64% (49-77%, p=0.04), respectively. 

The deviation of measured from expected lung volumes in these phases could 

be partly explained by the linear conversion of the sinus-shaped breathing 

curve to reconstruct the consecutive 4D-CT data sets. 

Conclusions: The pressure sensor-based breathing curve corresponded in 

most cases with the actual relative lung volumes determined on reconstructed 

4D-CT. As long as 0%, 50% and 100% expiration phases are used for 4D 

target definition, these may be regarded to represent the actual breathing 

phases. 

219 oral 

RESPIRATORY GATED RADIOTHERAPY HAS A DIFFERENT 

NORMAL TISSUE SPARING EFFECT FOR LEFT- AND RIGHT-SIDED 

BREAST CANCER PATIENTS. 

K. Erven 1 , J. Hrbacek 1 , S. Petillion 1 , F. Van den Heuvel 1 , C. Weltens 1 , 

W. Van den Bogaert 1 

1 UNIVERSITY HOSPITAL LEUVEN, Radiotherapy, Leuven, Belgium 

Purpose: To determine the heart and lung sparing effects of gated radiotherapy 

for left- and right-sided breast cancer patients separately. To investigate 

the effect of gating in inspiration on the irradiated lung mass. 

Materials: Twenty breast cancer patients (10 left- and 10 right-sided), were 

consecutively enrolled in this study. They underwent a non-gated (NG) CTscan 

on the virtual simulator (Siemens Sensation OpenTM), followed by a 

CT-scan using prospective gating (PG). To perform the PG CT-scan, the RPM


system (VarianTM) was used to record the patients breathing pattern and 

coach them to breath deeply. A gated window was chosen in inspiration and 

by an automatic interface between the RPM system and the CT scanner, 

CT acquisition was triggered in this window. Target volumes (breast, internal 

mammary and median supraclavicular lymphnodes) and normal tissues 

(heart and lungs) were delineated on both the NG and PG CT-scans. For 

each patient a treatment plan was designed on both CT-scans, using a singleisocentric 

photon technique. Dose calculations were done with the AAA algorithm. 

Dose-Volume metrics were used to evaluate the normal tissue doses. 

Additionally, lung density data were calculated from the CT numbers to estimate 

the irradiated lung mass. 

Results: For left-sided patients, a significant reduction in mean heart dose 

[7.3 Gy (NG) to 3.9 Gy (PG), p


respectively. Comparing breast to other treatment sites, dose differences are 

similar but γ values are higher due to the presence of lung tissue in the beam 

which our method currently does not account for. 

Conclusions: When applying an off-axis correction for large EPID shifts and 

using a dose specification point, in vivo EPID dosimetry for breast treatments 

shows excellent results. The method is now used clinically in our department, 

and is the standard patient specific QA method. 

222 oral 

MONTE CARLO STUDY ON THE USE OF PIN POINT IONISATION 

CHAMBERS FOR SMALL FIELD DOSIMETRY 

F. Crop 1 , N. Reynaert 2 , G. Pittomvils 3 , L. Vakaet 3 , H. Thierens 2 

1 UGENT/UZ GENT, Medical physics/radiotherapy, Gent, Belgium 

2 UGENT, Medical Physics, Gent, Belgium 


Purpose: Our aim was to understand the influence of different spot sizes, 

location in penumbra and measuring depth on the correction factors for micro 

ionisation chambers in small field dosimetry. Classic (reference) dosimetry is 

not applicable in this setting as there is a state of electronic disequilibrium. 

Knowledge of the different factors for wall, central electrode, water to air and 

volume correction could lead to a correction model for clinical use of micro 

ionisation chambers. To this purpose, speed enhancements were introduced 

in the c++ EGS user code CScavity in order to calculate correction factors in 

limited time. 

Materials: The EGSpp user code cavity was adapted (CScavity) for faster 

calculation of correction factors. Correlated sampling and the use of multiple 

ionisation chamber locations was implemented in the code. We benchmarked 

CScavity against results in the literature and calculations with cavity. Cscavity 

was then applied in the calculation of different correction factors for small field 

settings: (1) central electrode correction, (2) wall correction, (3) water to air 

conversion and (4) volume correction. Pin Point (PP) 31016 and PP31006 

geometries were investigated in a 0.8x0.8cm field setting on a Synergy linac. 

Full BEAMnrc linac simulations were used as input for CScavity. The linac 

was first tuned against measurements, and spot size parameters were varied 

between gaussian 0.6mm FWHM and 2.0mm FWHM in order to investigate 

the influence on the correction factors. 

Results: Large efficiency increases up to 40 times were attained for calculating 

chamber correction factors in a single location. Large spot sizes resulted 

in less correction starting from the penumbra. Correction factors for 

measurements in the optimal measuring direction and within the central axis 

of the beam favor the slender geometry of the PP31006 model, but in the 

non-optimal direction this PP31006 model results in more severe correction 

compared to the PP31016 model. In the non-optimal direction, for small spot 

sizes (0.6mm FHWM), the PP31006 results in extremities in volume correction 

of 1.125(1) at 2mm off axis towards 0.831(2) at 5mm off axis. 

Conclusions: Fast calculations of correction factors are possible in Cscavity. 

The spot size of the incident electron beam on the target has an important 

contribution to the correction factors for micro ionisation chambers. In a 

general IMRT or stereotactic radiosurgery setting, the PP31016 results in an 

overall lesser correction. 

223 oral 

S 71 

ACCURACY OF MODERN DOSE CALCULATION ALGORITHMS IN 

LUNG TISSUE 

H. Piersma 1 , T. Nuver 2 , P. Koken 1 , E. Damen 2 

1 

VU UNIVERSITY MEDICAL CENTRE, Radiotherapy, Amsterdam, Netherlands 

2 

THE NETHERLANDS CANCER INSTITUTE, Radiotherapy, Amsterdam, 

Netherlands 

Purpose: Correct modelling of the penumbra broadening in lung tissue is 

essential to make an accurate estimate of target coverage and dose to the 

organs at risk. The accuracy of penumbra broadening and absolute dose values 

calculated by two modern treatment planning algorithms (AAA-Eclipse & 

Collapsed Cone (CC)-Pinnacle) was investigated. This study was a continuation 

of earlier work on pencil beam algorithms done by Engelsman et al. 

(2001). 

Materials: Measurements were performed in an inhomogeneous lung phantom 

and in a homogeneous polystyrene phantom. The lung phantom consisted 

of cork slabs (16cm) with on top and at the bottom a 2cm polystyrene 

slab. A polystyrene sphere (=5cm) was positioned at the geometrical centre 

of the cork layers.6MV (AAA and CC) and 15MV (AAA) or 18MV (CC) 

AP-beams were planned. The dose was prescribed at the isocentre, which 

was located in the centre of the sphere. The 95% isodose encompassed 

the PTV (sphere+1.5cm margin) in the isocentre plane perpendicular to the 

beam axis. The plan calculated for the lung phantom was also used for the 

homogeneous measurements.Dose profiles were measured with absolutely 

calibrated Gafchromic film at 10 different depths in the phantoms.From the 

calculated and measured profiles the following parameters were determined 

for the lung and homogeneous phantom: absolute dose values along the central 

axis, penumbra width (PW:80%-20%), beam fringe (BF:90%-50%) and 

position of the 95% points. For PW, BW and 95% points the relative change 

between the inhomogeneous and the homogeneous phantoms were also derived. 

Results: AAA: 6 + 15 MVLung phantom: absolute dose values agreed within 

2.5%. For both energies PW and BF values agreed within 2mm, except 

at 5cm depth (4mm). The 95% points differed less than 2mm. Homogeneous 

phantom: differences of PW, BF and 95% points were smaller than 

2mm.However, calculated relative changes of PW and BF and 95% points 

were underestimated up to 5mm for 15 MV at 5cm. For 6 MV these values 

were: PW (2mm), BF (1mm), 95% points (3mm). CC: 6 MVLung phantom: 

measured absolute dose values agreed within 1.6% for 6 MV. PW and 

BF were slightly overestimated (2 and 3mm respectively); 95% points were 

underestimated by 3mm.Homogeneous phantom: differences for PW, BF 

and 95% points were 1, 2 and 2mm respectively.Calculated relative changes 

were: PW (2mm), BF (1mm) and 95% points (2mm). CC: 18 MVPreliminary 

data showed larger differences than would be expected based on the AAA 15 

MV data. The reason for this is currently unclear. 

Conclusions: For AAA (6+15 MV) and CC (6 MV) good agreement is found 

between calculations and measurements in lung tissue which indicates correct 

modelling of the penumbra broadening. Agreements are much better 

than with PB algorithms. The larger differences for the CC 18MV beam need 

further investigation. 

224 oral 

EXPERIMENTAL VERIFICATION OF A NEW PROTON PENCIL BEAM 

IMPLEMENTATION, WITH A SCANNED PROTON BEAM 

N. Tilly 1 , E. Traneus 1 , A. Ahnesjö 1 , M. Jansson 2 , T. Ersmark 2 , L. 

Glimelius 2 , D. Hedfors 2 

1 NUCLETRON SCANDINAVIA AB, Uppsala, Sweden 

2 RAYSEARCH LABORATORIES AB, Sveavägen 25, SE-111 34 , Stockholm, 

Sweden 

Purpose: The increased interest in active scanning proton therapy calls for 

the development and implementation of accurate treatment planning algorithms 

for state-of-the-art scanned proton beam delivery. A source beam 

model, a pencil beam algorithm and efficient treatment plan optimization were 

implemented in a commercial treatment planning system. In this work, experimental 

verification of the beam model and the proton dose engine was 

performed. 

Materials: Measurements were carried out using the compact proton scanning 

system at the The Svedberg Laboratory (TSL) in Uppsala, Sweden 

(Lorin et al 2000, Tilly et al 2007). A fluorescent screen viewed via a mirror 

and a CCD camera was mounted parallel, as well as orthogonal to the central 

beam axis in a PMMA phantom. The fluorescent screen/CCD camera setup 

has proven to be an excellent detector for two-dimensional measurements of 

dynamic dose delivery (Boon et al 2000), however, it does not yield a linear 

response with proton energy, but shows a quenching for higher LETs (Tilly 

et al 2007). To account for this effect, a proton energy dependent correction 

factor was experimentally obtained by measuring the dose at several depths 

in PMMA with both a cylindrical Farmer ion chamber and the screen/CCD 

camera setup for a mono-energetic scanned field. 

Results: An image obtained with the screen positioned parallel to the central


beam axis, sandwiched in the center of 8 cm PMMA is shown in the left panel 

of Figure 1. The PMMA phantom was here placed directly behind a 2 cm 

thick block of brass on top of a corresponding 2 cm block of PMMA, with the 

brass/PMMA interface in the center of the 14x14 cm 2 proton field. The lack of 

lateral equilibrium as an effect of the inhomogeneity is here clearly visualized 

as a drop shaped hot spot in the joint penumbra region of the two halves of 

the field. The corresponding pencil beam calculation corrected for quenching 

is shown in the right panel of Figure 1. 

Conclusions: A new proton pencil beam implementation was experimentally 

verified utilizing a state-of-the-art actively scanned proton beam system. 

Measurements show that the beam source model, proton range and 

multiple Coulomb scattering calculations yield results within clinical acceptance.Figure 

1. Relative intensity of the fluorescent screen (left panel) and the 

corresponding pencil beam calculation corrected for quenching (right panel) 

for a scanned 14 x 14 cm 2 proton field where the upper half of the field contains 

a brass pocket starting at the surface, extending 2 cm into the PMMA 

phantom. The screen is placed parallel to the central beam axis and mounted 

in the center of 8 cm PMMA, starting directly after the brass pocket. 

225 oral 

INVESTIGATION OF ADEQUATE ACCEPTANCE CRITERIA FOR THE 

GAMMA-INDEX IN SCANNED ION RADIOTHERAPY 

S. Lahrmann 1 , O. Jäkel 2 , C. P. Karger 1 

1 GERMAN CANCER RESEARCH CENTER (DKFZ), Dept. Of Medical Physics 

in Radiation Oncology, Heidelberg, Germany 

2 HEIDELBERG ION THERAPY (HIT), GERMAN CANCER RESEARCH CENTER 

(DKFZ), Dept. Of Medical Physics in Radiation Oncology, Heidelberg, 

Germany 

Purpose: In photon IMRT the gamma-index is routinely used to assess the 

results of dose verification measurements. For photons, acceptance criteria 

of 3 % as well as 5 % of the maximum dose and 3 mm for the distance to 

agreement (DTA) are widely accepted. For heavy ions, adequate acceptance 

criteria have not been systematically investigated. 

Materials: At GSI (Darmstadt, Germany) dose verification for scanned carbon 

ion therapy is performed with a 3D stack of 24 ionization chambers. Acceptance 

criteria of 5 % for the mean deviation as well as for the standard 

deviation of deviations between measured and calculated dose are currently 

applied. For this purpose, only measurement positions in moderate dose gradients 

are considered. Now, a tool for calculation of the gamma-index in 3 

dimensions has been implemented into the verification software. Acceptance 

criteria of 3 % / 3 mm (a), 5 % / 2 mm (b), 6 % / 1 mm (c) and 7 % / 2 

mm (d) have been retrospectively analyzed in 40 treatment fields verified and 

accepted at GSI. The resulting treatment plan acceptance rates were compared 

to those found with current criteria. Additionally, the gamma-index was 

recalculated after correcting the measured dose by the mean dose deviation 

obtained for the respective measurement using acceptance criteria of 5 % / 2 

mm. 

Results: A mean dose deviation of (-2.8 + 5.0) % (1 SD) was observed and 

80 % of the individual measurement positions showed deviations below + 

7.0 %. The range of the mean gamma-indices for individual patients was 

0.24 1.12 (a), 0.25 0.95 (b), 0.24 0.94 (c) and 0.19 0.74 (d). A fraction 

of 0.81 (a), 0.85 (b), 0.82 (c) and 0.89 (d) of all measurement positions in 

all fields yielded a gamma-index below 1. When the measured doses were 

corrected for the mean dose deviation, mean gamma-indices of 0.22 0.82 

with a fraction of 0.89 below 1 were obtained (5 % / 2 mm, compare fig. 1). 

Conclusions: Using acceptance criteria of 7 % for dose deviation and 2 

mm for DTA, the same acceptance rates were obtained as with the currently 

applied criteria. Simulations showed that the dose tolerance limit of 7 % can 

be reduced to 5 %, if the beam model is improved. Figure 1: Distribution of 

gamma-indices applying acceptance criteria of 5 % / 2 mm after correction of 

the measured values for the mean dose deviation. 

226 oral 

POTENTIAL OF INDIVIDUAL BIOLOGICALLY OPTIMIZED IMRT FOR 

BREAST CANCER 

B. Costa Ferreira 1 , P. Mavroidis 2 , M. Adamus-Górka 3 , R. Svensson 3 , B. 

Lind 3 

1 

AVEIRO UNIVERSITY AND INST. PORTG. ONCOLOGY OF COIMBRA, Physics 

Department, Aveiro, Portugal 

2 

LARISSA UNIVERSITY HOSPITAL, Medical Physics Department, Larissa, 

Greece 

3 

KAROLINSKA INSTITUTET, Department of Medical Radiation Physics, 


Purpose: The full potential of biologically optimized radiation therapy (RT) 

can be maximized with the prediction of individual patient radiosensitivity prior 

to treatment. Unfortunately, the available dose-response parameters, derived 

from clinical trials, reflect an average radiosensitivity of the population. 

Materials: A breast cancer patient was chosen for analysing the effect of the 

variation of individual radiosensitivity on the optimal dose distribution. Thus, 

deviations from the average biological parameters, describing tumour, heart 

and lung response, were introduced covering the range of patient radiosensitivity 

reported in the literature. Two treatment configurations of 3 and 7 

biologically optimized intensity modulated beams were employed. 

Results: The reference dose distribution, which is the optimal for the average 

patient biology shows that in the 3-field IMRT plan the complication-free 

tumour control probability, P+, was 91.0% due to a probability of tumour control, 

PB, of 94.4% and a probability of heart, PH, and ipsilateral injury, PLL, of 

0.4% and 1.1%, respectively, whereas in the 7-field IMRT plan P+ was 93.9% 

with a PB of 95.9% and PH and PLL of 0.4% and 0.4%, respectively. In 

the 3-beam plan, the difference in P+ between the optimal dose distribution 

(when the individual patient radiosensitivity is known) and the reference dose 

distribution, which is the optimal for the average patient biology, ranges up 

to 13.9% when varying the radiosensitivity of the target volume, up to 0.9% 

when varying the radiosensitivity of heart and up to 1.3% when varying the 

radiosensitivity of lung. Similarly, for the 7-beam plan, the differences in P+ 

are up to 11.8% for the target, up to 1.6% for heart and up to 0.9% for left 

lung. When the radiosensitivity of the most important tissues in breast cancer 

RT were simultaneously changed, the maximum gain in outcome was as high 

as 7.7%. 

Conclusions: Even for radiosensitive patients a simple treatment technique 

is sufficient to maximize outcome, since no significant benefits were obtained 

with a more complex technique using 7 intensity modulated beams portals. 

The impact of the dose-response uncertainties on the treatment outcome 

was clinically insignificant for the majority of the simulated patients. Nevertheless, 

the development of predictive assays to select patients with extreme 

radiosensitivity or radioresistance may significantly improve the quality of individual 

biologically optimized RT.


227 oral 

COMPARISON OF CTV-PTV MARGIN RECIPES IN TWO DUTCH 

RANDOMIZED PROSTATE CANCER TRIALS 

I. Kassim 1 , M. Dirkx 1 , B. Heijmen 1 

1 ERASMUS MC-DANIEL DEN HOED CANCER CENTER, Radiation Oncology, 

Rotterdam, Netherlands 

Purpose: The CTV-PTV margin recipes applied in a former Dutch dose escalation 

trial (CKVO), a new hypofractionated trial (HYPRO) and a modified 

version of this protocol (HYPRO-exp) were compared. While for the CKVO 

and HYPRO plans the rectum was excluded for the boost PTV, the representative 

target volume (RTV), i.e., the volume that should be treated taking 

positioning uncertainties into account, was used for planning in HYPRO-exp. 

The plans were compared focussing on target coverage and rectum dose. 

Materials: Treatment plans were generated for 36 prostate cancer patients 

using XIO version 4.3.3 (CMS Inc). For CKVO, the CTV-PTV margin was 10 

mm, which was reduced to 5mm (0 mm at the dorsal side) for the boost phase. 

A 3D conformal radiotherapy technique was used, delivering 68 Gy to PTV1 

and sequentially 10 Gy to the boost volume (PTV2). Because in the HYPRO 

study on-line position verification on markers in the prostate is applied, the 

CTV-PTV margins around the prostate could be reduced to 6 mm (7.5 mm 

at the caudal side) and10 mm around the seminal vesicles. For the boost 

phase these margins were reduced to 5 mm, but no margins was taken at the 

overlap with the rectum. The margins recipe for HYPRO-exp was identical 

to HYPRO, except that the zero CTV-PTV margins towards the rectum was 

omitted. For the HYPRO and HYPRO-exp plans a simultaneous integrated 

boost technique using IMRT was applied delivering 72.2 Gy to PTV1 and 78 

Gy to PTV2. For all the plans, the dose to the rectum was compared using 

V40, V50 V70 and the equivalent uniform dose (EUD), calculated with α=5. 

In addition the dose coverage and minimum dose of the RTV were quantified. 

Results: Compared to CKVO the rectal EUD was reduced by 5.6±2.1 Gy for 

HYPRO and by 5.2±1.9 Gy for HYPRO-exp. V50 and V70 were significantly 

lower as well (p


ment procedure that can be applied quickly after the I-125 implant. This would 

allow to discover any significant underdosage while the patient is still under 

anaesthesia in the treatment position. 

Materials: To achieve this, we need to reconstruct accurately the 3D position 

of each implanted seed and to co-register it with the prostate contour. The reconstruction 

of the seed 3D positions is performed with an isocentric imaging 

system adjacent to the treatment table. Seven cone-beam images acquired 

over an angle of 60o are used to generate a seed-only volume (figure 1) relying 

on a tomosynthesis-based filtered reconstruction. A 3D connected component 

analysis is then performed on this seed-only volume to extract each 

seed position. A graphical user interface (GUI) has been developed to allow 

the user to visualize the final seed positions and to conveniently introduce corrections 

in the positioning of seeds, if needed. The co-registration between 

the tomosynthesis-based seed positions and the TRUS-based prostate contour 

is performed by applying the same rigid transformation as the one derived 

from the best match between the planned and the reconstructed seed 

positions. A phantom and a clinical study (24 patients) were carried out to 

validate the technique. 

Results: A phantom study has demonstrated a very good localization accuracy 

of (0.4±0.4)mm. The reconstruction algorithm also provides the seed 

orientation with an uncertainty of (10±8)o. This enables us to achieve a more 

accurate dose calculation by including anisotropy effects. In a patient study 

with an average of 56 seeds per implant, the automatic tomosynthesis-based 

reconstruction yields a detection rate of 96% of the seeds and less than 1.5% 

of false-positives. With the help of the GUI, the user can achieve a 100% 

detection rate in an average of 3 minutes. Patient dose analyses have shown 

a substantial decrease in D90 and V100 between the planned and the intraoperative 

dosimetry, respectively (11±8)% and (4±3)%. 

Conclusions: This seed reconstruction and prostate contour fusion method 

provides accurate intra-operative dosimetry, in less than 10 minutes extra 

time to the whole implantation procedure. We believe that this technique may 

be used to discover considerable underdosage and to improve the dosimetric 

coverage by potentially reimplanting additional seeds. 

230 oral 

CAN RESPIRATORY COACHING FOR 4D CT EMULATE FREE 

BREATHING DURING THE TREATMENT COURSE? 

G. Persson 1 , D. E. Nygaard 1 , M. Olsen 1 , A. N. Pedersen 1 , L. Specht 1 , 

S. Korreman 1 

1 RIGSHOSPITALET, COPENHAGEN UNIVERSITY HOSPITAL, Department of 

Radiation Oncology, Copenhagen, Denmark 

Purpose: Using 4D CT and finding the midventilation scan for planning in 

lung cancer radiotherapy diminishes the risk of introducing a systematic error 

caused by tumor motion. The image quality of 4D CT depends on breathing 

regularity. Respiratory coaching may improve regularity, facilitating less 

motion artifacts. We question the safety of coached planning 4D CT without 

coaching during treatment. For this purpose we investigated whether it is 

possible to coach to a more regular breathing close to the free breathing. 

Materials: Eleven volunteers, recruited among health professionals in the department, 

went through auditive respiratory coaching on three different days 

within a two week period. The RPM system (Varian) was used to track the 

respiratory motion. On all days, free breathing and two coaching modes were 

recorded. All breathing curves are being analyzed regarding amplitude to find 

inter- and intrasession variations. We assumed that first day’s free breathing 

simulated an uncoached 4D CT planning and compared the mean amplitude 

to the mean amplitudes of the free and coached breathing from day two and 

three. We equally assumed that the coached breathing from day1 simulated 

a coached 4D CT planning and compared the mean amplitude to the mean 

amplitudes from the free and coached breathing from day two and three (two 

tailed T-test, p


prostate CTVs available. An algorithm was written to determine both the 

optimum 3D translation and the rotation angles required in order to align the 

repeat CTVs with their planning CTV. Angles considered were those possible 

through gantry rotation, couch rotation and couch tilt. The optimum shifts 

and angles were determined as those that will minimise the volume of the 

repeat scan CTV lying outside the volume of the planning CTV. Three different 

situations were investigated: 1) 3D translation only (3 DoF), 2) rotation after 

applying the optimum 3D translation (3+3 DoF) and 3) translation and rotation 

optimised concurrently (6 DoF). 

Results: For the bladder, the overall average volume percentage (across 

scans and patients) of the repeat CTV not included in the planning scan CTV 

was reduced from 13.2% without IGRT to 9.4%, 9.1% and 8.9% with 3DoF, 

3+3 DoF and 6 DoF, respectively. For 12 of the 62 repeat bladder CTVs, 

a reduction greater than 5% in the volume not covered was obtained when 

including rotation. For the prostate, the overall average of the repeat CTV 

not enclosed by the planning CTV was reduced from 25.5% without IGRT to 

16.3%, 16.2% and 16.1% with 3DoF, 3+3 DoF and 6 DoF, respectively. The 

largest reduction obtained using 6 DoF in stead of 3 DoF for the prostate was 

3%. 

Conclusions: When treating either the bladder or prostate alone, translational 

IGRT correction was by far the most important action necessary to 

ensure alignment of the repeat CTV with the planning CTV. As it is the largest 

positional deviations that determine the margins required, further studies of 

the impact in terms of margins are currently being performed. 

233 oral 

ASSESSMENT OF RESIDUAL DEFORMATION FOR ONLINE 

IMAGE-GUIDED RADIOTHERAPY FOR PROSTATE CANCER USING 

IMPLANTED FIDUCIAL MARKERS 

J. de Boer 1 , E. J. Rijkhorst 1 , R. de Jong 1 , M. van Herk 1 , J. Lebesque 1 , 

J. J. Sonke 1 


Purpose: Prostate organ motion is often corrected for using a couch shift assuming 

rigid-body prostate motion. The purpose of this study was to quantify 

prostate using implanted fiducial markers. 

Materials: For three patients, three 0.35 x 30 mm gold markers (Visicoil R○) 

were implanted transperineally in the prostate using transrectal ultrasound 

guidance. The markers were aligned approximately along the CC-axis. For 

each patient, a series of cone-beam CT (CBCT) scans were obtained as part 

of the treatment protocol. The prostate in each CBCT scan was registered 

onto the planning CT scan using two different methods: 1) rigid 3D greyvalue 

registration using a shaped region of interest of the prostate gland and 

seminal vesicles, and 2) rigid chamfer matching of the markers. Differences 

between these registration methods in both translations and rotations were 

calculated. Furthermore, inter-fraction residual marker deformation was assessed 

by modeling each marker by a B-spline with degree 3, and 5 to 7 

control points. Rigid motion was compensated for by using the marker registration 

results. Residual displacements of the markers between planning CT 

and CBCT were calculated for thirty evenly spaced points along the B-spline. 

Results: Patients included in this study manifested large rotations of the 

prostate gland giving rise to substantial differences between the 3D greyvalue 

registration and the marker registration. For the three main axes the 

following differences (mean ± standard deviation) were found: 0.3 ± 0.6 mm 

(LR), -0.5 ± 2.1 mm (CC) and -0.7 ± 1.5 mm (AP) for translations and 3.9 ± 

5.6 ◦ (LR), -0.1 ± 1.9 ◦ (CC) and -0.2 ± 2.1 ◦ (AP) for rotations. The residual 

marker displacements (mean ± standard deviation) after marker registration 

were -0.1 ± 0.6 mm (LR), 0.2 ± 1.5 mm (CC) and 0.0 ± 0.8 mm (AP). The 

largest residual displacements were found near the apex of the prostate. 

Conclusions: Early results show substantial differences between grey-value 

registration and marker registration of CBCT scans, especially around the 

left-right axis, indicating differential organ motion between prostate gland and 

seminal vesicles. Residual marker displacements were relatively small indicating 

limited deformation of the prostate’s internal anatomy. 

234 oral 

ELECTROCARDIOGRAPHIC (ECG) FINDINGS AMONG EARLY 

STAGE BREAST CANCER PATIENTS AND ASSOCIATION WITH RA- 

DIATION TREATMENT (RT) TECHNIQUE AND BASELINE CARDIAC 

RISK FACTORS 

C. Correa 1 , J. Liao 2 , V. Ferrari 3 , H. Litt 4 , L. Solin 5 , E. Harris 6 

1 


2 

UNIVERSITY OF PENNSYLVANIA, R, Philadelphia PA, USA 

3 

UNIVERSITY OF PENNSYLVANIA, Department of Internal Medicine, 

Philadelphia PA, USA 

4 

UNIVERSITY OF PENNSYLVANIA, Radiology, Philadelphia PA, USA 

5 

ALBERT EINSTEIN UNIVERSITY, Radiation Oncology, Philadelphia, USA 

6 

MOFFITT CANCER CENTER, Radiation Oncology, Tampa, USA 

Purpose: The cardiac effects of modern tangential beam RT for early stage 

breast cancer are not well quantified. ECG abnormalities may be predictive 

S 75 

of radiation related cardiac injury. 

Materials: A total of 1,140 patients who underwent RT for stage I-II breast 

cancer from 1977-1994 were screened for ECGs performed before RT and after 

completion of RT. All ECGs were analyzed by the same electronic system 

and verified by a cardiologist. The probability of ECG abnormalities in relation 

to RT fields were evaluated by univariate analysis with the Kaplan-Meier 

method and compared by the log-rank test. Multivariate Cox proportional hazards 

regression analysis was performed among a smaller subset of patients 

(58% of patients with ECGs) who had complete baseline cardiac risk factor 

information to evaluate for RT effects while accounting for baseline cardiac 

risk. If there were few events, multivariate analysis was not performed (NP). 

Results: A total of 198 patients had both pre-RT and post-RT ECGs. The 

median time of post-RT ECGs was 6.1 years (range 0.25 21 years). After 

correcting for pre-existing ECG abnormalities, univariate analysis showed 

that several ECG findings were associated with left-side and internal mammary 

nodal irradiation (IMN): ST segment abnormalities left ventricular hypertrophy, 

right bundle branch block, left anterior fascicular block, repolarization 

abnormalities, and ectopic rhythm (Table 1). When corrected for baseline cardiac 

risk factors, IMN RT versus none (HR = 12) and left versus right-side RT 

(HR = 5.6) were associated with an increased risk of left ventricular hypertrophy. 

The highest risk was among patients treated with left-side plus IMN RT 

as compared to right-side RT alone (HR = 62). Similarly, left-side plus IMN 

RT was associated with an increased risk of right bundle branch block (HR 

= 101) and ectopic rhythm (HR = 165) as compared to right-side RT alone. 

When tests for interaction were performed, left-side plus IMN RT and blood 

pressure together conferred a greater risk for left ventricular hypertrophy than 

either alone, p for interaction = 0.03. The right bundle branch and left anterior 

fascicular conduction pathways are located anteriorly in the heart in anatomic 

close proximity to the IMNs. Left ventricular hypertrophy occurs in the left ventricle 

of the heart, with more probable irradiation of this structure with left-side 

and IMN RT. ST segment abnormalities can be located in various anatomic 

locations in the heart. Clinically, ST segment abnormalities are associated 

with myocardial ischemia, while left ventricular hypertrophy is indicative of 

left ventricular wall thickening. In general populations ECG abnormalities are 

predictive of cardiovascular morbidity and mortality. 

Conclusions: Left-side and regional nodal RT using modern techniques for 

early stage breast cancer may be associated with an increased risk of ECG 

abnormalities that is of potential clinical significance. The risk of ECG abnormalities 

may be modified by baseline patient cardiac risk factors. 

235 oral 

SORENESS AND SENSITIVITY TO SUN EXPOSURE 10 TO 16 

YEARS AFTER BREAST CANCER RADIOTHERAPY 

D. Lundstedt 1 , M. Gustafsson 2 , P. Malmström 3 , K. A. Johansson 4 , D. 

Alsadius 1 , A. Sundberg 2 , U. Olofsson 5 , E. Holmberg 6 , H. Anderson 7 , G. 

Steineck 8 , P. Karlsson 9 

1 SAHLGRENSKA UNIVERSITY HOSPITAL AND SAHLGRENSKA ACADEMY, 

Department of Oncology and Clinical Cancer Epidemiology, Gothenburg, 

Sweden 

2 SAHLGRENSKA UNIVERSITY HOSPITAL AND SAHLGRENSKA ACADEMY, 

Department of Radiophysics and Clinical Cancer Epidemiology, Gothenburg,


Sweden 

3 

LUND UNIVERSITY HOSPITAL, Department of Oncology, Lund, Sweden 

4 

SAHLGRENSKA UNIVERSITY HOSPITAL, Radiophysics, Göteborg, Sweden 

5 

SAHLGRENSKA UNIVERSITY HOSPITAL AND SAHLGRENSKA ACADEMY, 

Oncologic Centre and Clinical Cancer Epidemiology, Gothenburg, Sweden 

6 

SAHLGRENSKA UNIVERSITY HOSPITAL, Oncologic Centre, Göteborg, 

Sweden 

7 

LUND UNIVERSITY, Department of Cancer Epidemiology, Malmö, Sweden 

8 

SAHLGRENSKA ACADEMY AND KAROLINSKA INSTITUTET, KAROLINSKA 

UNIVERSITY HOSPITAL, Department of Clinical Cancer Epidemiology, 

Gothenburg and Stockholm, Sweden 

9 

SAHLGRENSKA UNIVERSITY HOSPITAL, Oncology, Göteborg, Sweden 

Purpose: We have some information on breast-irradiation toxicity but lack 

data on long-term adverse effects from a randomized study. 

Materials: Between 1991 and 1997, 1187 women with stage I-II lymph node 

negative breast cancer were randomized in a Swedish study of breast conservation 

and axillary dissection with or without postoperative radiotherapy. 

The breast parenchyma was treated with 48 to 54 Gy in two Gy fractions five 

days weekly using tangential photon beams. In 2007 the group comprised 

417 alive and recurrence free women born 1931 or later. At the end of 2007, 

we collected data from this group using a validated questionnaire consisting 

of 333 questions regarding symptoms and quality of life. In order of believed 

likelihood, we hypothesized radiation to induce: breast discomfort, edema, 

skin hyper sensitivity, erysipelas, heart or lung symptoms, rib fractures or decreased 

shoulder mobility. 

Results: In total 366 (87.8%) women returned the questionnaires. We found 

no statistically difference between the groups for edema, erysipelas, heart 

or lung symptoms, rib fractures or shoulder mobility. However, in the group 

with postoperative radiotherapy nine percent reported soreness in the treated 

breast at least once a week (RR 14.5; 95% CI 1.9 108), 28 percent slight to 

substantial soreness in response to touching the treated breast (RR 2.4; 95% 

CI 1.5 3.9), 35 percent slight to substantial soreness in response to pressure 

on the treated breast (RR 2.2; 95% CI 1.5 3.3), 21 percent slight to substantial 

hypersensitivity in response to touching the treated breast (RR 3.9; 95% 

CI 2.0 7.9), 20 percent slight to substantial discomfort in the breast area in 

response to wearing tight clothing (RR 2.1; 95% CI 1.2 3.7), eight percent 

reported more sensitivity to sun exposure on the treated side compared to 

the contra lateral breast (RR 6.3; 95% CI 1.5 27.5) and five percent that sun 

exposure or warmth had slight to substantial effects on their quality of life (RR 

8.8; 95% CI 1.1 67.8). 

Conclusions: Women with stage I II breast cancer treated with breastconserving 

surgery and postoperative radiotherapy report more soreness and 

discomfort in the irradiated breast, as well as increased sensitivity to sun exposure 

10 to 16 years after their treatment, compared to women having undergone 

surgery only. 

236 oral 

PHASE II STUDIES ON ACCELERATED IMRT IN BREAST CARCI- 

NOMA: PRELIMINARY RESULTS 

A. G. Morganti 1 , S. Cilla 2 , V. Valentini 3 , C. Digesù 1 , G. Ferrandina 4 , F. 

Deodato 1 , G. Macchia 1 , G. Garganese 4 , L. Di Lullo 5 , F. Scarabeo 6 , L. 

Caravatta 1 , N. Cellini 3 , A. Piermattei 2 , G. Scambia 7 

1 

"JOHN PAUL II" CENTER FOR HIGH TECHNOLOGY RESEARCH AND 

EDUCATION IN BIOMEDICAL S, Radiotherapy, Campobasso, Italy 

2 


EDUCATION IN BIOMEDICAL S, Physics, Campobasso, Italy 

3 

POLICLINICO UNIVERSITARIO "AGOSTINO GEMELLI", CATHOLIC UNIVER- 

SITY, Radiotherapy, Rome, Italy 

4 


EDUCATION IN BIOMEDICAL S, Department of Gynaecology, Campobasso, 

Italy 

5 

GENERAL HOSPITAL, Oncology, Isernia, Italy 

6 

GENERAL HOSPITAL, Surgery, Isernia, Italy 

7 

POLICLINICO UNIVERSITARIO "AGOSTINO GEMELLI", CATHOLIC UNIVER- 

SITY, Department of Gynaecology, Rome, Italy 

Purpose: Simplified techniques of IMRT in postoperative irradiation of conservative 

resected breast carcinoma have been proposed. Aim of this analysis 

was to evaluate the preliminary results in terms of dosimetric parameters 

and acute toxicity of two clinical studies on accelerated IMRT-based postoperative 

radiotherapy. These results are compared with those recorded in an 

historical control group (CG) of patients treated with "standard" 3D postoperative 

radiotherapy. 

Materials: The primary end-point of the MARA (Modulated Accelerated Radiotherapy 

in Adjuvant treatment of Breast Carcinoma) studies was late toxicity. 

Secondary end-points were acute toxicity, local control and overall survival. 

In the MARA-1 study, patients with low risk of local recurrence were 

enrolled and the aim was to reduce the total duration of treatment. Patients 

with medium-high risk of recurrence were enrolled in the MARA-2; the aim 

was to achieve both an improvement of TCP (Tumor Control Probability) and 

a slight reduction of treatment duration. In the CG, two conformally shaped 

wedged tangential beams (energy: 6-10 MV) were used. In the MARA-1 and 

MARA-2 studies, two tangential fields were used, and the dose was divided 

into a larger segment, including the whole irradiated breast (energy: 6-10 

MV), and a smaller segment (10-15 MV), directed to the larger and deeper 

part of the gland, to improve dose homogeneity. Prescribed dose to the breast 

was 50.4 Gy (1.8 Gy/fraction) in the CG, 40 Gy (2.5 Gy/fraction) in MARA-1 

study, and 50 Gy (2 Gy/fraction) in MARA-2 study. A sequential boost dose of 

10 Gy (2 Gy/fraction) was delivered by an electron beam in the CG. Patients 

in MARA-1 and MARA-2 studies received a concomitant boost with 2 tangential 

wedged and conformally shaped photon beams (daily dose: 25 cGy and 

40 cGy, respectively). Therefore total dose to the tumor bed was 60.4 Gy, 44 

Gy and 60 Gy in CG, MARA-1 and MARA-2 studies, respectively. No patients 

received concurrent chemotherapy during RT. 

Results: 332 patients were included in the analysis (MARA-1: 99 pts; MARA- 

2: 102 pts; CG: 131 pts). Dosimetric analysis showed Dmax and V107% 

reduction (p < 0.001) and Dmin improvement in the PTV (p < 0.001) in patients 

treated with IMRT. Moreover, excluding patients treated with prophylactic 

nodal irradiation, a significant improvement of lung (ipsilateral) V80% 

(p=0.030) and V95% (p 2 acute skin toxicity was 33.6%, 13.1% 

and 45.1% in the CG, MARA-1 and MARA-2, respectively (p3 months), no late grade 3 toxicity occurred, one patient 

had late grade 2 diarrhoea. 

Conclusions: IMAT ± cisplatin has low toxicity and is excellent in rendering 

irresectable cervical cancer resectable with low toxicity. All operated patients 

had tumour free resection margins. No pelvic relapses have yet been observed 

in this patient group.


238 oral 

OPTIMIZATION OF INTRA-UTERINE BRACHYTHERAPY (BT) IN 

CERVIX CANCER: DO WE NEED TO DEFINE THE PRE-TREATMENT 

TUMOUR? 

D. Williamson 1 , J. Jezioranski 1 , A. Beiki-Ardakani 1 , J. Xie 1 , D. Zwahlen 

1 , W. Levin 1 , L. Manchul 1 , A. Fyles 1 , M. Milosevic 1 

1 PRINCESS MARGARET HOSPITAL/UNIVERSITY OF TORONTO, Radiation 

Medicine Program, Toronto, Canada 

Purpose: GEC-ESTRO guidelines recommend optimizing BT plans for cervix 

cancer using both high and intermediate risk CTV’s (HRCTV and IRCTV) and 

dose constraints for rectum, sigmoid colon and bladder. However, IRCTV can 

be difficult to relate to patient and tumour geometry at BT due to tumour 

regression and normal tissue deformation. We compared plans based on HR 

and IRCTV’s vs. HRCTV alone to evaluate the necessity of incorporating the 

IRCTV in the optimization process. We also evaluated pre-treatment factors 

to determine patients benefiting from IRCTV delineation. 

Materials: Thirty-three patients undergoing PDR BT for stage IB-IVA cervical 

cancer following external beam radiotherapy (EBRT) and concurrent cisplatin 

were analysed. 10 patients had evidence of myometrial invasion on 

pre-treatment pelvic MR imaging. All patients received EBRT 45-50 Gy/25 

fractions followed by PDR delivered with single intracavitary application using 

an intra-uterine line source without vaginal colpostats. Delineation of target 

structures and organs at risk (OAR’s) conformed to GEC-ESTRO guidelines. 

Two optimized BT plans were derived retrospectively. The first was optimized 

to deliver 35-40 Gy to the HRCTV and 20 Gy to IRCTV as per GEC-ESTRO 

guidelines, constrained to total (EBRT+BT) OAR dose limits of EQD2Gy 2cc 


in case of IMRT was 62.8 Gy (range: 56.0-68.8 Gy; 95% CI: 57.7-67.8 Gy), 

as compared to 58.8 Gy (range: 51.6-66.3 Gy; 95% CI: 56.0-61.5 Gy) in 

case of IMPT (p


243 oral 

FOLLOW-UP OF NON-SMALL CELL LUNG CANCER (NSCLC) 

PATIENTS AFTER (CHEMO)RADIOTHERAPY WITH 18FDG-PET-CT 

SCANS: A PROSPECTIVE STUDY 

J. Van Loon 1 , J. Grutters 1 , A. M. Dingemans 2 , G. Bootsma 3 , W. Geraedts 

4 , C. Pitz 5 , P. Lambin 1 , D. De Ruysscher 1 , J. Simons 6 

1 

MAASTRO CLINIC, Radiation Oncology, Maastricht, Netherlands 

2 

MAASTRICHT UNIVERSITY HOSPITAL, Department of Pulmonology, 


3 

ATRIUM MEDICAL CENTRE, Department of Lung Diseases, Heerlen, 

Netherlands 

4 

ORBIS MEDICAL CENTRE, Department of Pulmonology, Sittard, Netherlands 

5 

LAURENTIUS HOSPITAL, Department of Lung Diseases, Roermond, 

Netherlands 

6 

SINT JANS GASTHUIS, Department of Lung Diseases, Weert, Netherlands 

Purpose: Follow-up of patients treated with curative intent for NSCLC with 

imaging is of unproven benefit. Most patients with a recurrence have symptoms 

at time of presentation. Furthermore, a major restriction of both chest 

X-ray and CT is the poor discriminating capacity between residual or recurrent 

disease and post-treatment changes. Because the accuracy to stage 

NSCLC with 18FDG-PET-CT is superior to CT, we hypothesized that FDG- 

PET-CT scans 3 months after the beginning of radiotherapy (RT) could lead 

to early detection of recurrences that could be amenable for radical treatment. 

Materials: Patients with stage I-III NSCLC, treated with curative intent by 

means of (chemo)radiation, were prospectively evaluated (NCT00573040; 

NCT00572325). All patients underwent a planned whole body FDG-PET- 

CT scan three months after the start of RT, irrespective of the presence of 

symptoms. The CT-and PET findings were first reported independently and 

thereafter jointly by the radiologist and the PET-scan specialist. A recurrence 

was defined as either locoregional or distant. Within 1 week after the PET-CT 

scan, patients were evaluated clinically by history taking and clinical examination. 

Results: Of the 100 included patients, 79 had locally advanced disease, defined 

as UICC stage III. The median time interval between the start of RT and 

the PET-CT scan was 15 ± 3.9 weeks (range: 6-26 weeks). In 24/100 (24 %, 

95 % CI 17-33 %) patients a recurrence was detected. Seven were locoregional, 

7 distant, and 10 both locoregional and distant. 16/24 (67%, 95 % CI 

47-82 %) patients with a recurrence were symptomatic. No curative treatment 

could be offered to any of those patients. Of the 8/24 (33 %, 95 % CI 18-53 %) 

patients without symptoms, 4 recurrences were only detected with PET, while 

4 were detected with CT only. Of the 4 patients with a recurrence detected 

on PET, 3 were diagnosed with potentially curable disease. One patient had 

isolated adrenal metastases that were treated with surgery, while one patient 

had a local recurrence, treated with radical RT. The third patient had both resectable 

local residual disease and an isolated adrenal metastasis. For the 4 

patients with a recurrence detected on CT, only palliative treatment could be 

offered. 

Conclusions: PET-CT scanning 3 months after curative treatment for NSCLC 

led to the detection of potentially curable recurrences in 3/100 (3 %, 95 % CI 

1-8 %) patients. These 3 patients were all asymptomatic and recurrences 

were only detected by PET, not with CT. The cost-effectiveness of routine 

PET-CT scanning is currently being investigated. 

244 oral 

IORT IN PANCREATIC CANCER: A JOINT ANALYSIS IN 5 EURO- 

PEAN CENTERS 

G. R. D’Agostino 1 , V. Valentini 1 , G. C. Mattiucci 1 , A. G. Morganti 1 , F. 

Calvo 2 , J. L. Garcia-Sabrido 3 , F. Sedlmayer 4 , G. Fastner 4 , R. Krempien 

5 , P. Passoni 6 , V. Di Carlo 7 , M. Reni 8 

1 

UNIVERSITÀ CATTOLICA DEL SACRO CUORE, Radiotherapy, Rome, Italy 

2 

HOSPITAL GREGORIO MARANON, Radiotherapy, Madrid, Spain 

3 

HOSPITAL GREGORIO MARANON, Surgery, Madrid, Spain 

4 

UNIVERSITAT PARACELSUS, Radiotherapy, Salzburg, Austria 

5 

UNIVERSITAT HEIDELBERG, Radiotherapy, Heidelberg, Germany 

6 

OSPEDALE SAN RAFFAELE, Radiotherapy, Milan, Italy 

7 

OSPEDALE SAN RAFFAELE, Department of Endocrine-Pancreatic Surgery, 

Milan, Italy 

8 

OSPEDALE SAN RAFFAELE, Medical Oncology, Milan, Italy 

Purpose: This joint analysis of 5 European Centers explores in a large sample 

of pancreatic cancer patients submitted to primary surgery the role of 

intra-operative radiation therapy (IORT) in local control and survival. 

Materials: Patients with a histologic diagnosis of carcinoma of the pancreas 

undergoing surgery with radical intent and IORT were considered eligible 

to this analysis. Preoperative and/or postoperative external radiotherapy + 

chemotherapy were permitted at discretion of the study investigators. Local 

control (LC), and overall survival (OS) were calculated from the time of 

surgery + IORT by the Kaplan-Meier actuarial method. 

Results: From 1985 to 2006 a total of 270 patients were enrolled in the study 

from 5 European Institutions. Radical surgery was performed in 91.5% of 

S 79 

cases, preceded by ERT in 63 cases (RT-CT in 38% of them), and complicated 

by adverse events in 59 cases (33.9%). Overall, only 4 patients died 

as a result of surgical complications. After surgery + IORT, 106 patients received 

further ERT (RT-CT in 7.5% of them). Median follow-up was 96 months 

(range 3-180). Median LC was 15 months, whereas 5-year LC was 23.3%, 

significantly associated with tumor size (p


246 oral 

HEALTH-RELATED QUALITY OF LIFE AFTER PERMANENT I-125 

BRACHYTHERAPY AND EXTERNAL BEAM RADIOTHERAPY FOR 

PROSTATE CANCER - A MATCHED PAIR COMPARISON 

M. Pinkawa 1 , B. Asadpour 1 , B. Gagel 1 , M. D. Piroth 1 , S. Nussen 1 , M. 

Kehl 1 , H. Borchers 2 , G. Jakse 2 , M. Eble 1 

1 

UNIVERSITY HOSPITAL RWTH AACHEN, Radiooncology, Aachen, 

Germany 

2 

UNIVERSITY HOSPITAL RWTH AACHEN, Urology, Aachen, Germany 

Purpose: The aim of the study was to compare health-related quality of life 

(HRQOL) after permanent I-125 brachytherapy (BT) and external beam radiotherapy 

(RT) for prostate cancer. 

Materials: A group of 104 patients (52 in each group) has been surveyed 

prospectively before RT/BT (time A), at the last day of RT or one month after 

BT (time B), and a median time of 16 months after RT/BT (time C) using 

a validated questionnaire (Expanded Prostate Cancer Index Composite). 

The multi-item scale scores were transformed lineary to a 0-100 scale, with 

higher scores representing better HRQOL. All patients in the RT-group were 

treated with 1.8-2.0Gy fractions up to a total dose of 70.2-72.0Gy. BT was 

performed as monotherapy with a prescription dose of 145Gy. Only patients 

who answered all questionnaires have been included. Pairs were matched 

according to following criteria: age±5years, prostate volume±10cc, use of 

antiandrogens, and erectile function. 

Results: Mean patient age was 67years, mean prostate volume 39cc in 

both groups. Neoadjuvant antiandrogens have been used in 15 cases, respectively. 

HRQOL results are shown in the Table (* indicating significant 

differences between RT and BT). Patients scheduled for BT presented with 

significantly better urinary bother and urinary obstructive/irritative scores before 

treatment. Other scores did not differ >5 points. However, compared 

to baseline levels, both urinary function and urinary bother scores (obstructive/irritative 

scores in particular) decreased more after BT both at time B and 

time C. Bowel function and bowel bother scores tended to be higher after 

BT, with a lower percentage of patients with painful bowel movements (BT: 

12%/27%/15%; RT: 19%/52%/35% at time A/B/C, respectively; p


Materials: From January 2003 to November 2007, 162 patients with histologically 

proven high risk prostate cancer were recruited to this study. High 

risk were patients with PSA> 20 ng/ml or with at least 2 of the following characteristics: 

PSA of 11 to 20, Gleason Score > 6, T>2b. All patients received 

hormonal therapy for 9 months. Seventy four patients were randomized to 

receive 80 Gy in 40 fractions in 8 weeks (control arm), and 73 were allocated 

to receive 62 Gy in 20 fractions in 5 weeks, 4 fractions per week, (hypofractionated 

arm). All patients were treated with 3D conformal radiation therapy 

(3DCRT). The median follow-up (FU) is 25 months (range 2-47). Of the 90 patients 

with a >2 year FU, 71 patients, 34 in the control and 37 in the hypofractionated 

arm, underwent a 2-yr prostate re-biopsy with, at least, 6 specimens 

for each lobe, depending on the size of the residual prostate. 

Results: In 65 of the 71 patients (91%) undergone prostate re-biopsy, the histological 

examination showed only extended post-XRT modifications. Residual 

atypic cells were found in the remaining 6 patients (9%), 2 in the control 

and 4 in the hypofractionation arm. Only 1 of the 6 patients with positive biopsies 

is presently showing a PSA rise due to pelvic node metastases, while 

the remaining 4 are still b-NED with a PSA13cc 15Gy. 

Results: SRS was applied on 150 lesions in 86 patients (mean 1.7 lesion 

per patient, mean KPS 86). Median radiation dose was 21 Gray, median 

PTV 5.1 cc. Whole brain radiation therapy (WBRT) had been administered 

earlier to 11 patients (13%), and 12 patients (14%) received SRS together 

with WBRT. The median overall survival was 6.2 months after SRS and 9.7 

months from diagnosis of brain metastasis. Actuarial survival rates at 6, 12 

and 24 months after SRS were 53%, 35% and 12% respectively. Multivariate 

analysis revealed that a KPS of 90 or 100 (p = 0.009) and female sex (p 

= 0.003) were associated with a longer survival. A complete response was 

achieved in 11 metastases (12%), partial response in 48 (53%) and stable 

disease in 29 (31%), resulting in a short-term local control rate of 94%, which 

was maintained at the last follow-up MR in 70 of 90 (78%) evaluable lesions. 

Actuarial local control rates at 6, 12 and 24 months were 82%, 63% and 57%. 

Radiation dose ≤ 15 Gy (p = 0.017) and KPS < 90 (p = 0.013) were independent 

predictors of a shorter time to local failure. Six patients had a second 

SRS following progressive intracranial disease with a median survival of 7.4 

months. Five patients showed evidence of radionecrosis after a median of 

5.8 months with a median survival in these patients of 14.8 months. Addition 

of WBRT to SRS neither led to improvement of survival nor of local control. 

Conclusions: Survival was mainly determined by KPS following SRS for 

brain metastasis,. Local failure was associated with relatively low radiation


doses of 12-15 Gy delivered to a PTV of ≥ 13 cc. The potential of hypofractionated 

SRS for brain metastases of larger volume warrants further study. 

252 oral 

MAGNETIC RESONANCE SPECTROSCOPY OF BRAIN IS CORRE- 

LATED WITH RESULTS OF COGNITIVE TESTS FOR CHILDREN 

AFTER PROPHYLACTIC CRANIAL IRRADIATION (PCI) 

R. Tarnawski 1 , K. Ficek 1 

1 CENTRE OF ONCOLOGY MSC MEMORIAL INSTITUTE, Radiotherapy, 

Gliwice, Poland 

Purpose: To correlate results of cognitive tests with changes of brain 

metabolism studied by Magnetic Resonance Spectroscopy (MRS) in vivo. 

Materials: A group of thirty children treated with PCI because of ALL aged 4- 

17 (mean 9 years) and a group of 15 children aged 5-15 (mean 10 years) who 

received only chemotherapy because of ALL were examined using MRI/MRS 

tomography system (Elscint Prestige 2T). Irradiated children received doses 

of 18 Gy in 10 fractions 5 to 7 years before MRI/MRS studies, also control 

group of ALL patients treated without PCI was examined 5 to 7 years after 

the end of chemotherapy. Children underwent also simple cognitive tests, 

testing separately concentration, memory, and school learning ability. Relative 

intensities of the signals (choline [Cho], creatine [Cr], N-acetyl aspartate 

[NAA], myo-inositol, lactate, and lipids) were obtained by numeric integration 

of fitted signals. Four voxels located in opposite temporal and parietal lobes 

were examined. Means from four voxels were calculated for each metabolite 

ratio. 

Results: MR imaging revealed demyelinisations in group of 5 children in PCI 

group. No significant abnormalities were found by MRI in control group. MRS 

showed changes in brain metabolism in group of 10 children in PCI group and 

1 child in control group. Decrease of NAA/Cr and increase of Cho/Cr ratio 

were observed. Decrease of NAA/Cr is often described as an impairment of 

neuronal function, increase of Cho/Cr is related to damage of white matter. 

Results of MRS were closely correlated with cognitive concentration testing 

but not with memory and school learning ability. Decreased concentration 

ability was observed for 50% of children in PCI group and 40% of children in 

control group. Logistic model including NAA/Cr and Cho/Cr ratio was built. It 

was possible to predict results of concentration test with 87% sensitivity and 

75% specificity. 

Conclusions: Decrease of NAA/Cr ratio and increase of Cho/Cr ratio are 

closely correlated with results of cognitive testing in group of children who 

received PCI as a part of ALL treatment. 

253 oral 

OBSERVER VARIABILITIES OF SUV MEASUREMENTS OF 18F- 

FDG PET-CT BEFORE RADIOTHERAPY. CONSEQUENCES FOR 

THE PREDICTION OF SURVIVAL IN PATIENTS WITH A GLIOBLAS- 

TOMA. 

B. Vanhauten 1 , S. B. Abdulfatah 2 , R. Houben 1 , R. Debougnoux-Huppertz 

1 , M. van Kroonenburgh 2 , G. Bosmans 1 , P. Lambin 3 , B. Baumert 3 

1 

UNIVERSITY HOSPITAL MAASTRICHT, Dept. Radiation-Oncology (MAAS- 

TRO), Maastricht, Netherlands 

2 

UNIVERSITY HOSPITAL MAASTRICHT, Dept. Nuclear Medicine, Maastricht, 

Netherlands 

3 

UNIVERSITY HOSPITAL MAASTRICHT, Dept. Radiation-oncology (MAAS- 

TRO), GROW, Maastricht, Netherlands 

Purpose: To evaluate the potential influence of intra- and interobserver variability 

on the prognostic value of 18-FDG PET-CT prior to radiotherapy. To 

confirm reproducibility of preliminary data showing that high uptake of 18FDG 

on PET-CT scan before radiotherapy in glioblastoma could be a marker for reduced 

survival. 

Materials: Between 2003 and 2006, 72 patients were scanned with a combiend 

PET-CT for radiation treatment planning. Target volumes were determined 

by the use of both modalities, PET and CT. Based on the same definition 

of volumes of interest of white matter, max SUV uptake in the tumour 

and contra-lateral grey matter independent and blinded measurements were 

performed by 2 radiation-oncologists (RTO)(with a physicist) (n = 65) and a 

nuclear medical physician (n = 23)(NP). Qualitative (FDG uptake) and semiquantitative 

assessment with standardized uptake values (SUV) were performed. 

Values of SUV were compared to standardized volumes of white 

and grey matter in the normal brain which were determined for each patient 

on the CT part of the combined PET-CT scan. One repeated measurement 

was done by the same observer for a subgroup of patients (n = 20) in order 

to define intra-observer variability. Intra- and inter-observer variabilities were 

compared by paired the t-test. The influence of observer variability on prognostic 

value of PET was measured by Kappa as a measure for agreement. 

The prognostic value was defined by overall survival with the median tumour 

SUV as cut-off value. 

Results: Small confidence intervals and Kappa values show agreement for 

majority of measurements For the intra-observer variability a good agreement 

for repeated measurements was found. Good agreement of Kappa for SUV 

max and T/WM (0.9 and 0.6). The inter-observer variability was significantly 

different between radiation-oncologists for SUVmax and T/C, however with 

clinically small confidence intervals. Between RTO and NP a significant difference 

for T/C was found. There was insufficient agreement for the T/C ratio 

between RTO and RTO and NP (0.2 and 0.3). The T/Wm ratio was a significant 

prognostic factor for survival for both RTO, not for the NP presumably 

due to the small patient group measured by the NP. Prognostic value of PET- 

CT for survival was repeatable for 2 observers with a T/WM ratio ≤ 1.68. 

Conclusions: FDG-PET-CT can differentiate between prognostic subgroups 

within glioblastoma patients. Differences in intra- and inter-observer variability 

are small and measurements are repeatable (between 3 blinded observers 

major agreements) and do not influence clinical results. 

254 oral 

THE ROLE OF RADICAL HYPO-FRACTIONATION RADIOTHERAPY 

FOR DIFFUSE INTRINSIC BRAIN STEM GLIOMA IN CHILDREN: A 

PILOT STUDY. 

G. O. Janssens 1 , C. Gidding 2 , E. van Lindert 3 , F. Oldenburger 4 , C. 

Erasmus 5 , A. Schouten - Meeteren 6 , J. Kaanders 1 

1 

RADBOUD UNIVERSITY NIJMEGEN MEDICAL CENTRE, Dept. of Radiation 


2 

RADBOUD UNIVERSITY NIJMEGEN MEDICAL CENTRE, Dept. of Paediatric 


3 

RADBOUD UNIVERSITY NIJMEGEN MEDICAL CENTRE, Dept. of Neurosurgery, 


4 

ACADEMIC MEDICAL CENTRE AMSTERDAM, Dept. of Radiation Oncology, 

Amsterdam , Netherlands 

5 

RADBOUD UNIVERSITY NIJMEGEN MEDICAL CENTRE, Department of 

Paediatric Neurology, Nijmegen, Netherlands 

6 

ACADEMIC MEDICAL CENTRE AMSTERDAM, Dept. of Paediatric Oncology, 

Amsterdam , Netherlands 

Purpose: Despite aggressive approaches in many clinical trials done over 

the last three decades, the prognosis for children with diffuse intrinsic brain 

stem glioma remains dismal and most will die within 1 year of diagnosis. In 

order to reduce patient burden we investigated the feasibility of a radical hypofractionation 

schedule, given over 3 weeks, as an alternative to the standard 

conventional radiotherapy schedule (30 fractions of 1.8 Gy over 6 weeks). 

Materials: Between July 2004 and October 2007, 9 children, age 3 to 13, 

were treated in the radiotherapy departments of Nijmegen (n=7) and Amsterdam 

(n=2) by a hypo-fractionation schedule consisting of 13 fractions of 3 Gy 

(n=8) or 6 fractions of 5.5 Gy (n=1) given over 3 weeks (range 18 to 22 days). 

All patients included had symptoms for less than 3 months (mean 5.9 weeks) 

and at least 2 signs of the neurological triad (long tract signs, ataxia, cranial 

nerve deficit). On MR imaging, there was bilateral involvement of the pons 

in 8 of 9 patients, encasement of the basilary artery in 7 of 9 patients and 

extension into the cerebellar peduncle in 6 of 9 patients. Because of doubtful 

clinical and radiological features, a stereotactic biopsy was obtained in 4 

patients, all confirming a WHO grade 4 astrocytoma. 

Results: Symptom improvement occurred in all patients within 2 weeks after 

start of radiotherapy. Median time to progression from diagnosis was 4.9 

months. At a mean follow-up time of 15 months (range 3 to 41 months), 7 

patients have died. Six out of 7 patients died of local disease progression, 1 

patient died of CNS-infection but with tumor progression as proven by MRI. 

Median overall survival was 8.6 months. Median time to death after progression 

was 3.6 months. No grade 3 or 4 toxicity was observed. These results 

are not different from what is reported in the literature. According to a recently 

published review of clinical trials, the median time to progression, overall survival 

and time between progression and death ranged from 5 to 8.8, 7 to 16 

and 1 to 4.5 months, respectively, with conventional, accelerated or hyperfractionated 

schedules and other experimental treatment combinations (Hargrave


et al. Lancet Oncology. Vol 7; 241-247, 2006). 

Conclusions: The use of a radical hypofractionation radiotherapy regimen 

for children with a newly diagnosed diffuse intrinsic brain stem glioma is feasible 

and associated with no grade 3 or 4 toxicities. The median time to 

progression, overall survival and time to death after progression are within 

the range of published data. Therefore, 39Gy in 13 fractions of 3 Gy over 3 

weeks, could be considered as a good alternative to more protracted regimens. 

It offers patients quick symptom relieve and a temporary improvement 

in neurological signs and symptoms with minimal overall treatment time and 

a maximal escape from outpatient department transfers and hospital stay. 

255 oral 

CHEMOTHERAPY AND EXTERNAL BEAM RADIATION AS INITIAL 

TREATMENT FOR RETINOBLASTOMA 

M. Arguis 1 , M. Nieves 2 , C. Sabado 3 , M. Ramos 1 , S. Gallego 3 , M. Valdes 

1 , J. Sanchez de Toledo 3 , J. Giralt 1 

1 

VALL D’HEBRON HOSPITAL, Radiation Oncology, Barcelona, Spain 

2 

VALL D’HEBRON HOSPITAL, Department of Ophthalmology, Barcelona, 

Spain 

3 

VALL D’HEBRON HOSPITAL, Paediatric Oncology , Barcelona, Spain 

Purpose: Most patients with retinoblastoma have extensive disease within 

the eye at diagnosis. We retrospectively reviewed our experience treating 

retinoblastoma with chemotherapy and external beam radiotherapy as initial 

treatment to determinate effect on eye conservation, tumor control and complication 

rates. 

Materials: We analysed 33 eyes in 22 patients with retinoblastoma who received 

initial treatment with Chemotherapy and External Beam Radiotherapy 

(EBRT) at Vall d’Hebron Hospital from January 1996 to March 2006. Work 

up consisted on ocular examination under anesthesia, ocular ultrasonography 

and MRI. Indications for EBRT were retinal tumors larger than 12 mm 

in base and 8 mm in thickness, multifocal tumors, non confined vitreous or 

subretinal seeds and macular located tumor. Chemotherapy was 6 cycles 

of carboplatin, vincristine and etoposide every three weeks. Followed by 3-D 

conformal radiation with 6Mev photons to a total dose of 40 Gy in 20 fractions. 

Evaluation of tumor control, and toxicity were done by ocular examination under 

anaesthesia every two-three months. 

Results: Thirty-three eyes in 22 patients were analysed. Mean age at presentation 

was 9 months (range 1-95 months). Familial history was seen in 

4 patients (12%). Bilateral tumors were present in 12 patients (54%), and 

10 patients had unilateral tumors. According to the Internacional Classification, 

1 patient was at group A, 10 patients were at group B, 2 patients were 

at group C, 18 at group D and 2 at group E. 3 eyes were enucleated as 

initial treatment and 30 eyes underwent chemotherapy following EBRT. With 

a mean follow up of 60 months, local recurrence rate was 36%, no distant 

metastases were seen. Eye conservation rate was 74%. Overall survival was 

100% in this serie. Late complications included cataract (63%), retinopathy 

(1%). Only one patient developed a second tumor in the radiation field. 

Conclusions: Chemotherapy and external beam radiotherapy for retinoblastoma 

as initial treatment was associated with high eye conservation and tumor 

control rates Late complications are acceptable 

256 oral 

DISPARITY BETWEEN IN VIVO EGFR EXPRESSION AND 

ZIRCONIUM-89-LABELED CETUXIMAB UPTAKE ASSESSED WITH 

PET 

H. Aerts 1 , L. Dubois 1 , L. Perk 2 , P. Vermaelen 3 , G. van Dongen 2 , B. 

Wouters 1 , P. Lambin 1 

1 UNIVERSITY OF MAASTRICHT, Department of Radiation Oncology 

(MAASTRO), Maastricht, Netherlands 

2 VU UNIVERSITY MEDICAL CENTRE, Department of Nuclear Medicine and 

PET Research, Amsterdam, Netherlands 

3 UNIVERSITY HOSPITAL GASTHUISBERG AND KULEUVEN, Department of 

Nuclear Medicine, Leuven, Belgium 

Purpose: The epidermal growth factor receptor (EGFR) is highly expressed 

in a significant number of human malignancies and its expression is related 

with tumor aggressiveness and overall treatment resistance. The monoclonal 

antibody cetuximab (IMC-C225) is increasingly used in clinical settings as 

treatment modality in combination with more conventional therapies, such as 

radio and chemotherapy. However, a lot is unknown about patient-specific 

tumoral uptake and overall pharmacokinetics. Non-invasive quantification of 

in vivo cetuximab uptake could provide important diagnostic information, i.e. 

selecting patients beneficial for cetuximab treatment and evaluating therapy. 

Contributing to this knowledge, we developed and validated a novel probe using 

cetuximab labeled with the long-lived positron emitter Zirconium-89 ( 89 Zr) 

for positron emission tomography (PET) imaging. 

Materials: Tumor cells with varying EGFR expression levels were used for in 

vivo mice experiments. Human A-431 epidermoid carcinoma cells were designated 

as high, human glioblastoma U-373 MG and human colorectal adenocarcinoma 

HT-29 cells as intermediate, and human T-47D breast carcinoma 

S 83 

as low EGFR expressing cells. PET imaging with 89 Zr - labeled cetuximab 

(3.35 ± 0.14 MBq) was performed on tumor bearing NMRI-nu mice from 1 

to 120 hours post injection (p.i.). Confirmatory gamma-counting and Western 

blot quantification, using anti-EGFR monoclonal antibodies, was performed 

on ex vivo tumor material. 

Results: PET imaging revealed a clear uptake of 89 Zr - labeled cetuximab 

in EGFR positive tumors. Tumor-to-blood ratios in the high and intermediate 

EGFR expressing cell lines were significantly higher from 24 hours p.i. on, 

compared with the low expressing cells, and reached an optimum after 72-96 

hours p.i. However, a disparity was found between 89 Zr - labeled cetuximab 

uptake and in vivo EGFR expression levels. Normal tissue uptake was unaffected 

by the different tumor types. Gamma-counting and Western blotting 

confirmed the findings seen non-invasively. 

Conclusions: The 89 Zr - labeled cetuximab imaging probe represents a 

promising tool to evaluate the biologic and pharmacokinetic effects of cetuximab 

non-invasively. This probe reveals a disparity between in vivo EGFR 

expression levels and cetuximab uptake. In a general sense, the results indicate 

an overall disparity between antibody uptake and expression levels of a 

biologic target in a tumor, revealing additional mechanisms influencing tumor 

delivery. These additional mechanisms can explain why expression alone is 

not sufficient to explain therapy effects. 

257 oral 

GU TOXICITY AFTER RT FOR PROSTATE CANCER: DOSE MAPS 

AND DOSE SURFACE DATA TO IDENTIFY DOSE-EFFECT RELA- 

TIONSHIPS 

W. Heemsbergen 1 , M. Witte 1 , A. Al-Mamgani 2 , M. van Herk 1 , J. 

Lebesque 1 

1 NETHERLANDS CANCER INSTITUTE / ANTONI VAN LEEUWENHOEK 


2 ERASMUS MEDICAL CENTER, Radiation Oncology, Rotterdam, Netherlands 

Purpose: For prostate cancer patients treated with external RT, significant 

dose-effect relationships for late genitourinary (GU) toxicity are seldom found. 

Due to variable filling, the location and stretching of the bladder wall will be 

different from day to day, making the delineated bladder on the planning CT 

scan of limited predictive value for the true accumulated bladder dose during 

RT. We investigated whether dose maps of the area around the prostate were 

useful to detect dose-effect relationships for GU endpoints. Additionally, we 

analyzed available dose surface data of the bladder in a conventional way. 

Materials: Data of 552 patients of the Dutch escalation study (68 Gy vs 78 

Gy) were available. We constructed 3D dose maps of the region around the 

prostate on the planning CT (without considering the delineated bladder). For 

each patient the map gives the dose at a certain distance (≤ 4 cm) of the 

prostate surface, along radial lines from the centre of the prostate in many 

predefined directions, allowing comparisons of local dose between patients. 

Dose difference maps were calculated: differences between patients with and 

without a late GU complaint, for 3 endpoints (G3 obstruction, G2 nocturia 

and G2 pain/cramps needing medication). Furthermore, we determined the 

predictive value of the absolute and relative dose surface histograms (DSHs) 

of the delineated bladder receiving ≥ 5 Gy - ≥ 80 Gy, with dose steps of 5 

Gy (Cox regression). 

Results: Cumulative incidences at 7y were: 10 % (obstruction), 29 % (nocturia) 

and 16 % (pain/cramps). For obstruction (Fig. 1), the dose difference 

map indicated highly significant differences in the bladder area, with the 

largest dose differences (10-12 Gy, p ≈ 0.002) in the region (indicated with 

a circle) where the ureters end in the bladder (mean local dose about 40-50 

Gy). For nocturia, no significant differences were found. For G2 pain/cramps, 

dose differences were found in the bladder area close to the pubic bone. 

Analyses with absolute and relative DSHs showed only significant relationships 

between hotspots and GU endpoints. In the 78 Gy group, the absolute 

surface ≥ 80 Gy was associated with cramps/pain (p=0.008), obstruction 

(p=0.001) and nocturia (p=0.05). Surfaces > 80 Gy were present in about 15 

% of the 78 Gy patients. Hotspots (≥ 70 Gy) in the 68 Gy group were only 

associated with nocturia (p=0.04). 

Conclusions: Dose mapping in the bladder area indicated local dose-effect 

relationships predicting for late GU toxicity, which were not found with conventional 

DSH analyses. It is likely that bladder DSH analyses can also find 

these effects when the relevant area is delineated, providing more conclusive 

evidence for a true dose-effect relationship. We conclude that dose maps 

are complementary to DSH analyses; they are very useful for generating hypotheses 

to driving dose-effect analyses in the right direction.


258 oral 

ENHANCED EXPRESSION OF EARLY INJURY WITH INCREASED 

IRRADIATED RAT LUNG VOLUMES 

H. Faber 1 , P. van Luijk 1 , C. Muijs 2 , J. Schippers 3 , S. Brandenburg 4 , J. 

Langendijk 1 , R. Coppes 1 

1 

UNIVERSITY MEDICAL CENTER GRONINGEN, UNIVERSITY OF GRONINGEN, 

Department of Radiation Oncology, Groningen, Netherlands 

2 

UNIVERSITY MEDICAL CENTER GRONINGEN, UNIVERSITY OF GRONINGEN, 

Section of Radiation and Stress Cell Biology, Department of Cell Biology, 

Groningen, Netherlands 

3 

PAUL SCHERRER INSTITUT, Accelerator department, Villigen-PSI, 

Switzerland 

4 

KERNFYSISCH VERSNELLER INSTITUUT, Groningen, Netherlands 

Purpose: To improve the local control rates of thoracic malignancies by radiation 

dose escalation, more insight is required in dose distribution parameters 

that can be used as dose constraints in radiotherapy treatment planning. 

Recently, we showed in rat lung that low dose scattered over a large lung 

volume causes more early toxicity in terms of respiratory dysfunction than an 

extreme dose confined to a small volume (1). Two distinct pathologic lesions 

were identified in the early 8 weeks post-irradiation: vascular inflammation 

and parenchymal inflammation. Vascular inflammation translated into early 

respiratory dysfunction in completely irradiated lung, whereas, parenchymal 

inflammation was seen after higher doses and did not translate into respiratory 

dysfunction when 25% of lung volume was irradiated. In this study 

we further investigated the volume dependence of vascular and parenchymal 

inflammation and its translation to respiratory dysfunction. 

Materials: Radiation ports were designed using planning CT scans of 5 agematched 

animals. 88, 63 and 50% of rat lungs were irradiated with 10-22 Gy 

using 150 MeV protons. As a measure of global function, breathing rate was 

measured before and every 2 weeks after irradiation. At the peak of early 

pneumonitis (8 weeks post-irradiation) the level of vascular and parenchymal 

inflammation and expression of inflammatory cytokines (PCR) were determined 

and related to overall respiratory function. 

Results: After 50% lung volume irradiation, a clear dose response curve 

was observed for both vascular (starting at doses > 13 Gy) and parenchymal 

inflammation (starting at doses > 16 Gy). Increasing the volume reduced 

the dose at which vascular inflammation, cytokine expression and respiratory 

dysfunction was observed. Interestingly, the amount of infiltrates in the 

shielded part of the lungs increased with volume at lower doses. 

Conclusions: These data confirm that irradiation of a larger lung volume at 

a lower doses leads to more early respiratory dysfunction due to vascular 

inflammation when compared to lung irradiated to a smaller volume. These 

findings may be crucial for clinical treatment planning of dose escalations 

and choices for modern radiotherapy techniques such as proton therapy. (1) 

Novakova-Jiresova A, van Luijk P, van Goor H, Kampinga HH, Coppes RP. 

Changes in expression of injury after irradiation of increasing volumes in rat 

lung. Int J Radiat Oncol Biol Phys. (2007) 67:1510-8. 

259 oral 

A COMPUTER MODEL TO SIMULATE THE IMPACT OF RADIO- 

SENSITIVITY HETEROGENEITY ON TUMOUR CONTROL PROBA- 

BILITY 

C. Harting 1 , P. Peschke 2 , C. P. Karger 1 

1 GERMAN CANCER RESEARCH CENTER (DKFZ), Department of Medical 

Physics in Radiation Oncology, Heidelberg, Germany 

2 GERMAN CANCER RESEARCH CENTER (DKFZ), Clinical Cooperation Unit 

Radiation Oncology, Heidelberg, Germany 

Purpose: Tumour specific radio-sensitivity and proliferation activity may 

strongly influence the required therapeutic dose. The influence of these parameters 

on tumour control probability (TCP) is studied. 

Materials: A single cell and Monte-Carlo based model was developed to 

simulate tumour growth and radiation response. Only tumour and capillary 

cells located on a three-dimensional grid were considered. Tumour cells were 

characterized by their age, their ability to proliferate, their oxygenation status 

and their radio-sensitivity. Capillary cells were considered as sources of a 

radial-dependent oxygen profile and may proliferate. Simulation of tumour 

growth started with a single tumour cell embedded in a grid of equidistantly 

located capillary cells. Response to radiation was simulated by the linearquadratic 

(LQ) model taking into account the lower radio-sensitivity of poorly 

oxygenated tumour cells. Cell specific parameters, e.g. the cell cycle time 

or the tumour specific parameters α and β of the LQ-model were taken as 

random samples of a Gaussian distribution. Additionally, the inter-tumoural 

radio-sensitivity was varied. 

Results: For single doses, an inter-tumoural radio-sensitivity variation of 30 

% is necessary to show a significant decrease of the slope of the TCP curve 

while for a schedule with 40 fractions this effect was observed already at a 

variation of 10 %. If the same simulations were preformed without considering 

proliferation the dose response curve with and without an inter-tumoural 

radio-sensitivity variation of 10 % differ not significantly. 

Conclusions: Inter-tumoural radio-sensitivity variation influences TCPcurves. 

At fractionated schedules the influence is enhanced by proliferation. 

In the clinical situation, both parameters may vary throughout the tumour. 

Integration of data from biological imaging is required to better predict the 

response of individual tumours. A patient model is currently implemented 

260 oral 

PROTEIN EXPRESSIONS PREDICT RADIOSENSITIVITY IN HEAD 

AND NECK SQUAMOUS CELL CARCINOMA 

L. Farnebo 1 , L. Vainikka 2 , K. Roberg 2 

1 LINKÖPING UNIVERSITY HOSPITAL, ENT, Linköping, Sweden 

2 LINKÖPING UNIVERSITY HOSPITAL, Department of ENT, Linköping, 

Sweden 

Purpose: The aim of this study was to identify a panel of markers involved in 

apoptosis and/or growth control that in combination had a strong correlation 

to radiosensitivity. 

Materials: 42 head and neck squamous cell carcinoma (HNSCC) cell lines 

with an intrinsic radiosensitivity (IR) between 1.4 and 2.6 (measured with a 

clonogenic assay) and normal oral keratinocytes (NOK) were analysed with 

ELISA to evaluate the protein expression of EGFR, survivin, Bax, Bcl-2, Bcl- 

XL, HSP70 and COX-2. The mean expression was standardized to the mean 

for NOK within three ELISA analyses and the protein expression was classified 

into four groups 0-3 points no, small, middle or large changes. These 

cell lines were also analysed for p53 mutations and separated into groups 

depending on the type of p53 mutation they carried. Each mutation was 

awarded 1 point in the system named Number of Negative Points (NNP). 

Results: Our previous results have indicated that certain combinations of 

NNP for a specific tumour cell line correlates to its IR. In this study the NNP 

for survivin alone had a significant correlation to IR, (R=0.35, P=0.022). When 

statistically analysing the different combinations of the above mentioned proteins, 

the NNP sum of survivin, Bax, Bcl-2, Bcl-XL and COX-2 together had 

the strongest correlation to IR, (R=0.43, P=0.004). The NNP score for the p53 

mutations did not increase the correlation (R=0.42, P=0.006) when added to 

the other factors. 

Conclusions: In this study our results suggest that the combination of survivin, 

Bax, Bcl-2, Bcl-XL and COX-2 can predict the IR in HNSCC when using 

the NNP method. However, before using this method in the clinic, more factors 

at protein and gene level as well as an enhanced number of tumours 

has to be investigated. Even so, in the future we think that combinations of 

factors in the NNP system could be very influential in shaping the treatment 

of patients on an individual basis.


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P73 INDUCES PROFIBROTIC PAI-1 EXPRESSION SIMILAR TO P53 

M. Niemantsverdriet 1 , H. Langendijk 1 , H. Kampinga 2 , R. Coppes 1 

1 UNIVERSITY MEDICAL CENTER GRONINGEN, UNIVERSITY OF GRONINGEN, 


2 UNIVERSITY MEDICAL CENTER GRONINGEN, UNIVERSITY OF GRONIN- 

GEN, Department of Cell Biology; section Radiation Stress Cell Biology, 


Purpose: Radiation-induced fibrosis is a serious side effect of cancer treatment. 

Profibrotic proteins such as plasminogen activator inhibitor-1 (PAI-1) 

play major roles in the development of fibrosis via the modulation of extracellular 

matrix integrity. Many of these profibrotic genes can be induced by 

TGF-β and by members of the p53 family. Both pathways are induced by 

irradiation. Moreover, TGF-β and p53 act synergistic on the expression of 

several profibrotic genes, including PAI-1, resulting in high expression levels 

(Hageman et al 2005). In this study we further investigated the role of p53 

and its family member p73 on radiation and TGF-β induced PAI-1 expression. 

Materials: We used a p53 inducible cell line (Niemantsverdriet et al 2005) 

to study the effect of p53 and radiation on PAI-1 expression independently 

of each other. To further investigate radiation, TGF-β signalling and the expression 

of PAI-1 we used stable cell lines with integrated PAI-1 promoter 

luciferase constructs. To investigate the influence of p73 splice variants, we 

transfected these constructs in combination with plasmids expressing p53 

and p73 variants. 

Results: After expression of p53 and addition of TGF-β, radiation was not 

required for the synergetic activation of PAI-1, indicating that the synergy between 

radiation and TGF-β in p53 proficient cells is solely dependent on p53. 

In addition to radiation and p53, also p73 splice variants pronouncedly activated 

PAI-1 albeit to a lesser extent than p53. 

Conclusions: The synergystic effect of radiation and TGF-β and radiation 

on PAI-1 expression is p53 dependent. p53 family member p73 also stimulates 

the expression of PAI-1, similar to p53. This finding may be of great 

importance since many tumours overexpress p73 as well as TGF-β. Therefore, 

like p53 and TGF-β, p73 might be implemented in the normal tissue 

response to radiation by activating expression of PAI-1 and other profibrotic 

genes. Hageman J et al. Radiation and transforming growth factor-beta cooperate 

in transcriptional activation of the profibrotic plasminogen activator 

inhibitor-1 gene. Clin Cancer Res (2005) 11, 5956. Niemantsverdriet M et 

al. Radiation response and cell cycle regulation of p53 rescued malignant 

keratinocytes. Exp Cell Res. (2005) 310(1):237-47. 

262 oral 

EVALUATION OF REPOSITIONING ACCURACY OF PATIENTS 

USING A 3D-LASER SURFACE IMAGING SYSTEM 

T. Moser 1 , K. Schubert 2 , G. Sroka-Perez 3 , K. Herfarth 2 , J. Debus 3 , C. 

Karger 1 

1 

GERMAN CANCER RESEARCH CENTER (DKFZ), Dept. of Medical Physics 

in Radiation Oncology , Heidelberg, Germany 

2 

UNIVERSITY OF HEIDELBERG, Department of Radiation Oncology, 

Heidelberg, Germany 

3 

UNIVERSITY OF HEIDELBERG, Radiooncology and Radiotherapy, Heidel- 

berg, Germany 

Purpose: A 3D-laser surface imaging system is analysed for its applicability 

to determine the inter-fractional setup error in radiotherapy patients. 

Materials: A 3D-laser-imaging system (Galaxy, LAP Laser, Lneburg, Germany) 

is used to reconstruct 3D patient surfaces with high resolution. The 

system uses lasers designed for application in patients and is mounted at 

the ceiling of a tomotherapy unit (Hi"Art System, TomoTherapy, Madison, WI, 

USA). The reflections of the projected laser lines are recorded by a camera 

and a 3D-surface model of the patient is reconstructed. The actual patient 

position is then compared with that of a reference setup by image registration 

for a pre-defined region of interest. As a result of the registration, a setup correction 

with 4 or 6 degrees of freedom is calculated. This correction can be 

used to improve the setup of the patient. The calibration stability of the system 

was investigated. In addition, the setup of 7 patients (H&N: 2, Breast: 1, 

Thorax: 2, Prostate: 2) were analyzed to quantify the daily setup reproducibility 

after conventional positioning using room lasers as well as after correcting 

the setup by the Megavoltage CT of the tomotherapy unit. For this, the image 

of the actual treatment position was registered with that at the first fraction. 

Results: The data of the daily calibration showed daily variations of less than 

0.5 mm (mean value). MV-CT-based corrections were reliably detected by the 

system. The measured reproducibility after MV-CT-based setup corrections 

was largely dependent on the tumor site. For head and neck tumors, the 

initial setup showed already to be highly reproducible. As a mask system was 

used, MV-CT-based corrections of patient movements in the mask could not 

be detected by the surface imaging system and therefore the reproducibility 

measured by the imaging system decreased after setup correction. For the 

Breast tumor, the imaging system measured an increased reproducibility after 

the MV-CT-based correction for the thoracic tumors, this improvement was not 

seen. For prostate tumors, the improvement of the setup by the MV-CT was 

S 85 

partly reflected by the imaging system. 

Conclusions: The system is able to accurately detect translations of the patient. 

As the setup correction was performed on the basis of the MV-CTs as 

gold standard, the reproducibility of the reconstructed surface was strongly 

dependent on the correlation between surface and internal structures. For 

those tumors where this correlation is good, the absolute setup accuracy may 

be further increased by using the surface contours from the treatment planning 

CT rather than those acquired by the imaging system at the first fraction. 

These results have to be confirmed by further investigations. 

263 oral 

IMAGE QUALITY ASSESSMENT OF EXTRA CRANIAL 3D-CT DATA 

OBTAINED BY THREE DIFFERENT IMAGE GUIDED RADIATION- 

THERAPY DEVICES 

S. Nill 1 , K. Schubert 2 , U. Oelfke 1 

1 GERMAN CANCER RESEARCH CENTER, Department of Medical Physics in 


2 UNIVERSITY CLINIC HEIDELBERG, Department of Radiation Oncology, 


Purpose: Modern IGRT systems allow a fast acquisition of 3D-CT data of the 

patient in the treatment position. Naturally the different technical properties of 

these devices lead to images of different quality at various levels of imaging 

dose. In this work we quantitatively assess the image qualities of two MV 

based and one kV based IGRT-CT solutions by analyzing images of large QA 

phantoms designed to simulate the extra cranial patient anatomy. 

Materials: The following three devices were used to acquire images of different 

phantoms including a cylindrical CTDI and an elliptic body phantom 

with contrast inserts of different sizes at different positions: i) a Tomotherapy 

(Tomo) device using a fan beam with an imaging beam of 3.5MV, ii) the 

Siemens Primatom single slice fan beam CT with an energy of 130kV and an 

Artiste prototype equipped with MV(6MV) cone beam(CB) CT. The diameter 

of the CTDI body phantom was 32cm whereas the elliptic body phantom had 

a major-axis of 45cm. For each device three levels of imaging dose were 

selected. The CTDIw ranges from 0.78cGy to 16.55cGy. Based on individual 

inserts of these phantoms the dose dependency for the homogeneity (difference 

between central and outer ROI),signal to noise ratio, contrast to noise 

ratio (CNR) and the electron density to Hounsfield units(HU) correlation were 

compared. 

Results: As expected the kV fan beam system is superior to the other two 

systems for most of the evaluated imaging parameters. E.g. the CNR of the 

Tomo system is approx. 20% lower compared to the kV fan beam system 

and is even more reduced for the MV CB system(>200%). The difference 

between both MV systems is mostly due to the lower MV energy, the higher 

DQE and the fan beam of the Tomo system. The correlation of the e- density 

to HU is independent of the applied dose and the position of the inserts in 

the phantom for the kV and the Tomo system. For the MVCB system some 

differences are found especially for the lowest imaging dose used(2.67cGy). 

Conclusions: Based on the current results the normal CT scanner is still 

superior to all other imaging devices especially for the soft tissue contrast 

achievable with low imaging doses but especially the differences to the Tomo 

unit are not as large as observed for Head&Neck size phantoms. For the 

MV cone beam system a higher dose needs to be applied to the patient to 

obtain suitable images. Further investigations will include also kV CB images. 

Disclaimer: Partially funded by Siemens Med OCS.

S 86 PROFFERED PAPER TUESDAY, SEPTEMBER 16, 2008 


Gastro-intestinal Tumors 

268 oral 

RADIOTHERAPY IN GASTRIC CANCER: A SURVIVAL META- 

ANALYSIS 

V. Valentini 1 , F. Cellini 2 , G. C. Mattiucci 1 , M. Balducci 1 , G. R. D’Agostino 

1 , E. D’Angelo 1 , N. Dinapoli 1 , N. Nicolotti 3 , C. Valentini 4 , G. La Torre 3 

1 

UNIVERSITÀ CATTOLICA DEL SACRO CUORE, Radiotherapy, Rome, Italy 

2 

UNIVERSITA CAMPUS BIOMEDICO, Radiotherapy, Roma, Italy 

3 

UNIVERSITÀ CATTOLICA DEL SACRO CUORE, Department of Epidemiology, 

Rome, Italy 

4 

UNIVERSITÀ LA SAPIENZA, II FACOLTÀ, Radiotherapy, Rome, Italy 

Purpose: Gastric carcinoma has still an high mortality rate, despite a decrease 

in its incidence. It has an high risk of local recurrence or distant 

metastases. For this reason the survival rate at 3 or 5-years remain low. 

Resection is considered curative. Surgical techniques are today improving 

and standardized in order to allow an increment of the curative resection rate. 

Several studies about the possible utility of radiotherapy (RT) for the treatment 

of gastric carcinoma are now available. The objective of our meta-analysis is 

to assess the effectiveness of surgery combined with preoperative, intraoperative 

(IORT) or postoperative RT, to improve survival rate in patients with 

resectable gastric cancer. 

Materials: A computerized bibliographic research was conducted using Medline, 

Embase, Scopus. Only randomized controlled trials (RCTs), comparing 

survival of surgery with RT versus surgery alone, were included in this metaanalysis. 

Twelve studies were eligible. For each study a quality assessment 

was conducted using Chalmers scale. Data were extracted after 3 and 5 

years of follow-up from two independent researchers and combined using 

Review Manager 4.2.10. A sensitivity analysis was performed for treatment 

modality (pre/IORT/postoperative RT). 

Results: Maximum quality score was 48 and minimum 10. An overall significative 

increment of survival was found at 3 years [OR=1.29; CI 95% (1.00, 

1.68)] and 5 years [OR=1.46; CI 95% (1.04, 2.05)] (Fig. 1) using RT combined 

with surgery. Considering the studies with preoperative RT, we found 

a significant increment of survival at 3 years [OR=1.86; CI 95% (1.30, 2.66)] 

and 5 years [OR=1.48; CI 95% (1.02, 2.16)]. Considering the studies without 

IORT a significative increment of survival at 3 years [OR=1.37; CI 95% (1.15, 

1.63)] and 5 years [OR=1.58; CI 95% (1.04, 2.42)] was found. 

Conclusions: In patients with resectable gastric carcinoma, RT significantly 

increases survival at 3 and 5 years. Even though a significative increment 

at 3 or 5 years of survival in patients treated with preoperative RT or without 

IORT, new evidences are needed to better compare alternative. 

269 oral 

DEVELOPMENT AND EXTERNAL VALIDATION OF A PROGNOSTIC 

MODEL, BASED ON SEQUENTIAL FDG-CTPET, FOR PATHOLOG- 

ICAL COMPLETE RESPONSE OF ADVANCED RECTAL CANCER 

PATIENTS 

R. van Stiphout 1 , G. Lammering 1 , J. Buijsen 1 , S. Yu 2 , D. Rubello 3 , 

M. Gava 3 , C. Dehing 1 , M. Janssen 1 , L. Persoon 1 , R. Beets-Tan 1 , S. 

Krishnan 2 , B. Rao 2 , E. Postma 4 , C. Capirci 3 , P. Lambin 1 

1 

DEPARTMENT OF RADIATION ONCOLOGY (MAASTRO), GROW, UNIVER- 

SITY HOSPITAL MAASTRICHT, Maastricht, Netherlands 

2 

SIEMENS MEDICAL SOLUTIONS, Malvern, USA 

3 

DIVISION OF RADIOTHERAPY, S. MARIA DELLA MISERICORDIA HOSPITAL, 

Rovigo, Italy 

4 

MICC, UNIVERSITY MAASTRICHT, FACULTY OF HUMANITIES AND 

SCIENCES, Maastricht, Netherlands 

Purpose: Prediction of tumor response after chemoradiotherapy (CRT) might 

be helpful in individualizing treatment strategies, i.e. selecting patients who 

need less invasive surgery or another radiotherapy strategy in stead of resection. 

For rectal cancer it is known that 10-30% of the patients will respond 

with a pathologic complete response (pCR) after CRT. It is expected 

that adding data collected after CRT might lead to a more predictive model 

compared to evaluating only pretreatment data. In this study pretreatment 

data together with sequential FDG-CT/PET data are evaluated for their predictiveness 

of pCR in locally advanced rectal cancer patients. The resulting 

predictive model will be validated using an external dataset. 

Materials: Data from a collaborating group (Capirci et al.) consisting of 78 

rectal cancer patients were collected prospectively and used to build a model 

(training set). These patients received long-term CRT of 56 Gy and PVI 5- 

FU at 300 mg/m2. The collected pretreatment parameters included gender, 

age, tumor length, cT and SUVmax from CT/PET imaging. All patients underwent 

a CT/PET before treatment and 42 days after CRT. The absolute 

difference (DeltaSUVmax) and percent difference (Response Index, RI) of 

SUVmax between pre- and post-CRT PET scans were also included for evaluation. 

To identify cases responding with a pCR after CRT, the pathologic 

reports of the surgical specimens were reviewed for tumor stage after resection 

(ypT). Multivariate analysis was performed with a 2-norm support vector 

machine (SVM). The external validation dataset from MAASTRO consisted 

of 21 rectal patients receiving long-term CRT and was used to confirm the 

findings. Performance of the model was expressed as the AUC (Area Under 

the Curve) of the Receiver Operating Characteristic (ROC) and assessed with 

leave-one-out (LOO) cross-validation and with the external validation dataset. 

The maximum value of the AUC is 1.0, indicating a perfect prediction model, 

whereas a value of 0.5 indicates a random chance to correctly predict the 

pCR. 

Results: Chemoradiotherapy resulted in a pCR for 27% of the patients in 

the training set and 19% in the validation set. The best model resulted in 

the predictive parameters DeltaSUVmax, pretreatment SUVmax and tumor 

length with weights 0.13, -0.11 and -0.09 respectively. This model performed 

with a LOO AUC of 0.86 (95% CI 0.76-0.94) and a validation AUC of 0.91 

(95% CI 0.81-0.93). 

Conclusions: Evaluation of pretreatment data with dual CT/PET data resulted 

in a highly predictive model for pCR. Further increase of patient pool 

size and inclusion of extra variables from imaging, biomarkers, gene signatures 

etc. are expected to further increase the accuracy of prediction. 

270 oral 

PREOPERATIVE CHEMORADIATION FOR LOCALLY ADVANCED 

RECTAL CANCER. PRELIMINARY SAFETY RESULTS OF THE 

ACCORD 12/0405 PRODIGE-2 RANDOMIZED TRIAL. 

J. P. Gérard 1 , D. Azria 2 , S. Gourgou-Bourgade 3 , I. Martel-Laffay 4 , C. 

Hennequin 5 , P. L. Etienne 6 , E. François 7 , V. Vendrely 8 , G. De Laroche 9 , 

C. Montoto-Grillot 10 

1 

CENTRE ANTOINE LACASSAGNE, Radiotherapy, Nice, France 

2 

CENTRE VAL D’AURELLE, Radiotherapy, Montpellier, France 

3 

CENTRE VAL D’AURELLE, Montpellier, France 

4 

CENTRE LÉON BÉRARD, Lyon, France 

5 

HÔPITAL ST LOUIS, Radiotherapy, Paris, France 

6 

CLINIQUE ARMORICAINE DE RADIOLOGIE, Radiotherapy, St. Brieuc, 

France 

7 

CENTRE ANTOINE LACASSAGNE, Radiation Oncology, Nice, France 

8 

HÔPITAL ST ANDRÉ, Radiotherapy, Bordeaux, France 

9 

INSTITUT DE CANCÉROLOGIE DE LA LOIRE, St. Priest en Jarez, Cedex, 

France 

10 

FÉDÉRATION NATIONALE DES CENTRES DE LUTTE CONTRE LE CANCER, 

Paris, France 

Purpose: The FFCD 9203 [JCO 2006;24:4620-5] and the EORTC 22921 

[NEJM 2006;355:1114-23] trials showed superiority of neoadjuvant chemoradiation 

(CT-RT) to radiotherapy (RT) alone in terms of pathological Complete 

Response (pCR) (11%) and local control in locally advanced rectal cancers 

(LARC). The ACCORD 12/0405 PRODIGE-2 trial was initiated to optimize 

this neoadjuvant approach. 

Materials: Patients with T3 or resectable T4 or distal T2, N0-1-2 non 

metastatic rectal adenocarcinoma were randomized to either arm A: concurrent 

RT 45Gy/25f/5w + capecitabine (800mg/m/bid) (RT-Cap) or arm

TUESDAY, SEPTEMBER 16, 2008 PROFFERED PAPER 

B: concurrent RT 50Gy/25f/5w + capecitabine (800mg/m/bid) + oxaliplatin 

50mg/m/w (RT-Capox). Randomization was stratified by center, tumor site, 

and stage. Total mesorectal excision (TME) was scheduled 6 weeks after the 

end of CT-RT. Adjuvant chemotherapy was optional. The main end point of 

this trial was ypCR and the hypothesis was to increase it from 11% (arm A) to 

20% arm B). To test this hypothesis, 590 patients were needed. Secondary 

endpoints included R0 resection, conservative surgery, survival, local control 

and toxicity. This report presents preliminary safety data from the first 150 

patients with complete data 60 days after surgery. 

Results: Between 11/2005 and 02/2008, a total of 470 patients were randomized 

(234 and 236 in arm A and B, respectively) in 54 centers. Patient 

characteristics were well balanced at baseline: male 67%, median age 61 

years (range : 25-80), 61% low rectum, 87% T3 stage. No toxic death was 

observed. Compliance to surgery appeared satisfactory. 

Conclusions: The toxicities of RT-Capox arm (B) were acceptable and allowed 

continuation of the trial. Accrual will be finished in September 2008 

and results of the primary endpoint will be available in 2009. Updated and 

detailed safety results for the first 300 patients will be shown at the meeting. 

271 oral 

PREOPERATIVE CHEMO-RADIOTHERAPY REGIMEN WITH 

CAPECITABINE AND BEVACIZUMAB IN LOCALLY ADVANCED 

RECTAL CANCER. A FEASIBILITY STUDY 

C. Marijnen 1 , H. Rutten 2 , H. de Wilt 3 , M. Tesselaar 4 , J. Nuyttens 5 , J. 

Remmelzwaal 6 , K. Punt 7 , H. Martijn 8 , G. Hospers 9 , A. Cats 10 

1 

NETHERLANDS CANCER INSTITUTE, Radiation Oncology, Amsterdam, 

Netherlands 

2 

CATHARINA HOSPITAL EINDHOVEN, Surgery, Eindhoven, Netherlands 

3 

ERASMUS MEDICAL CENTER, Surgery, Rotterdam, Netherlands 

4 

LEIDEN UNIVERSITY MEDICAL CENTER, Clinical Oncology, Leiden, 

Netherlands 

5 

ERASMUS MEDICAL CENTER, Radiation Oncology, Rotterdam, Netherlands 

6 

NETHERLANDS CANCER INSTITUTE, Medical Statistics, Amsterdam, 

Netherlands 

7 

UMCN ST. RADBOUD, Medical Oncology, Nijmegen, Netherlands 

8 

CATHARINA HOSPITAL EINDHOVEN, Radiation Oncology, Eindhoven, 

Netherlands 

9 

UNIVERSITY MEDICAL CENTER GRONINGEN, Medical Oncology, Groningen, 

Netherlands 

10 

NETHERLANDS CANCER INSTITUTE, Department of Gastroenterology, 


Purpose: Radiotherapy (RT) combined with 5FU and bevacizumab seems a 

promising combination for locally advanced rectal cancer, but little data are 

available regarding toxicity and surgical complications. This multicenter study 

tests the feasibility of the combination of RT, capecitabine and bevacizumab 

in rectal cancer patients. 

Materials: 60 patients with a rectal adenocarcinoma with a threatened or involved 

circumferential resection margin (CRM) will be included. Treatment 

consists of radiotherapy (50 Gy in 25 fractions), capecitabine 825 mg/m2 bid 

and bevacizumab 5 mg /m2 iv on day -14, 1, 15 and 29, with surgery 6- 

10 weeks thereafter. An interim analysis was planned after inclusion of 15 

patients undergoing an abdominoperineal resection (APR) or Hartmann procedure. 

Results: So far, 23 patients (12 cT3, 11 cT4 tumors; have been entered who 

underwent 12 APR, 3 Hartmann procedures and 7 low anterior resections 

(LAR). One patient died before surgery. The study was put on hold when the 

number of 15 APR/Hartmann procedures was reached. During chemoradiotherapy 

(CRT), 7 grade 3 toxicities (4 skin, 2 diarrhea, 1 tenesmi) and 1 grade 

4 toxicity (anal mucositis) were reported. In addition, one patient developed 

an enteritis with diffuse uncontrollable bleeding at the end of the CRT. Eventually, 

this patient died before she could be operated on. Two small bowel 

perforations occurred: one 2 days after stopping the CRT, and one 19 days 

postoperatively, i.e. 70 days after the last bevacizumab. A third patient had an 

asymptomatic rectal wall perforation at the site of the primary tumor. Surgical 

complications consisted of 1 perineal dehiscence, 1 rectovaginal fistula after 

a stapling failure and 1 peroperative bleeding (5500 cc). Postoperatively, 1 

patient developed a pulmonary embolism. The CRM was negative in 20/22 

operated patients. Downstaging of the T-stage was observed in 18/21 patients. 

Of those, two patients had a complete pathological response, whereas 

9 patients had a ypT0-2 tumor. 

Conclusions: These results indicate that the combination of radiotherapy, 

capecitabine and bevacizumab is very effective. The toxicity pattern demon- 

S 87 

strates that extension of the study is warranted to further investigate the relation 

between radiation-induced enteritis and small bowel complications with 

this combination. 

272 oral 

ANASTOMOTIC LOCAL RECURRENCE OF RECTAL CANCER 

REMAINS AN IMPORTANT AND PREVENTABLE PATTERN OF 

FAILURE FOLLOWING TOTAL MESORECTAL EXCISION: LESSONS 

FOR RADIOTHERAPISTS 

B. ONeill 1 , D. Tait 2 , G. Brown 3 

1 

ST LUKE’S HOSPITAL, Department of Radiation Oncology, Dublin, Ireland 

Republic of 

2 

ROYAL MARSDEN HOSPITAL, Radiotherapy, London, United Kingdom 

3 

ROYAL MARSDEN HOSPITAL, Radiology, London, United Kingdom 

Purpose: High-resolution MRI has excellent soft-tissue resolution allowing 

identification of fascial layers and compartments. We analyse MR-defined 

patterns of recurrence of rectal cancer following total mesorectal excision 

(TME). These patterns have not been previously described by MR criteria. 

Patterns of failure may have changed in the TME era. 

Materials: A database of rectal adenocarcinomas treated at the Royal Marsden 

Hospital from 2000-2007 was analysed to identify pelvic recurrences following 

primary TME. T2-weighted high-resolution MRI imaging was available 

for 60 patients. Each pelvic failure was assigned one or more of the following 

pre-defined pelvic ’compartment’ patterns of recurrence: anastomotic, 

mesorectal margin, central, presacral, ’retro-presacral’ (a pattern not previously 

described), perineal, peritoneal and nodal (malignant pelvic recurrent 

nodal disease by MR-criteria). 

Results: Almost half (29/60, 48.3%) of recurrences were anastomotic; 

mesorectal margin 6.7% (4/60); central 6.7% (4/60); presacral 8.3% (5/60); 

’retro-presacral’ 10% (6/60); perineal 5% (3/60); peritoneal 1.7% (1/60) and 

nodal 16.7% (10/60; 2 of these, 3.3% presented as only malignant pelvic 

nodal disease as only site of recurrent disease; the majority, 8/60, 13.3%, 

were in association with another pattern of recurrence). High-resolution MR 

images of each pattern are presented. 

Conclusions: MRI has the ability to identify and classify pelvic recurrences 

of rectal cancer. While it is expected in the TME era that mesorectal margin 

recurrence would be a relatively uncommon pattern, anastomotic recurrence 

of rectal cancer remains an important and likely preventable pattern of 

failure following total mesorectal excision. Accurate documentation of these 

patterns of local recurrence is essential, as they indicate aetiology of local 

recurrences. Both the rate and pattern of local recurrence for rectal cancer 

are important for Radiotherapists, guiding patient selection and radiotherapy 

volumes for preoperative therapy. The images displays axial T2 weighted fast 

spin echo (TR 3900 TE 120) pelvic MRI for the same patient: a) Presacral (arrow, 

recurrence arising anteriorly from the presacral fascia) recurrence; and 

b) Retro-Presacral (arrow, recurrence arising posterior to the presacral fascia, 

causing characteristic ’bowing’ forward of the presacral fascia) recurrence. 

273 oral 

SEXUAL FUNCTION AFTER RADIOTHERAPY FOR RECTAL CAN- 

CER 

K. Bruheim 1 , M. G. Guren 1 , L. Balteskard 2 , E. Carlsen 3 , K. M. Tveit 1 

1 

ULLEVAAL UNIVERSITY HOSPITAL, Cancer Centre, Oslo, Norway 

2 

THE UNIVERSITY HOSPITAL OF TROMSØ, Oncology Department, Tromsø, 

Norway 

3 

ULLEVAAL UNIVERSITY HOSPITAL, Department of Gastrointestinal surgery, 

Oslo, Norway 

Purpose: Background: An increasing number of patients with rectal cancer 

receive pre- or postoperative radiotherapy. It is known that pelvic irradiation 

can affect sexual function, however, there is little knowledge of the prevalence 

and nature of sexual dysfunction in women, and limited knowledge about 

erectile dysfunction in men, after radiotherapy for rectal cancer 1 .


Materials: All Norwegian patients who received pre- or postoperative radiotherapy 

(46-50 Gy in 2 Gy fractions) for stage II-III rectal cancer in the 

years 1993-2003 were identified from The Norwegian Rectal Cancer Registry. 

Patients treated with surgery alone served as controls. The patients were 

without evidence of local recurrence or metastases. Self-administered questionnaires 

were sent by mail.Female patients received the Sexual Function- 

Vaginal-Changes Questionnaire (SVQ), and male patients the International 

Index of Erectile Function (IIEF), validated questionnaires previously used on 

cancer patients 2, 3 . The SVQ is a 20-item questionnaire that measures five 

main areas of female sexual function; sexual interest, lubrication, orgasm, 

pain, and satisfaction with sex life. In addition there are items on vaginal problems. 

The IIEF is a 15-item questionnaire, where each question is rated on a 

05 point scale, a high score indicates good sexual function. Five domains of 

male sexual function are measured; sexual desire, erectile function, orgasmic 

function, intercourse satisfaction, and overall satisfaction with sex life. The total 

score of each domain in the IIEF is the product of 2 or more different questions, 

and the total score ranges from 10 to 30. Questions about treatment 

for erectile dysfunction and ejaculation disorders were added. Comparison 

of symptoms between treatment groups was done with Pearson chi-square 

tests for categorical data, and Mann Whitney U-test for continuous variables. 

All tests were two-tailed, and a p-value < 0.05 was considered statistically 

significant. 

Results: Of 1010 eligible rectal cancer patients the questionnaires were returned 

from 498 patients, of whom 185 had received adjuvant radiotherapy, 

and 313 surgery alone. The mean age was 69 years (range 36-95), and 

the mean time since surgery was 5.6 years (range 2.3-12.8). The following 

results are based on preliminary analysis of the data.The SVQ was returned 

from 217 women, 74 had been irradiated, and 143 treated with surgery alone. 

Approximately 78% of the female patients had no or little sexual interest, 32 

% had been sexually active the last four weeks, there were no significant difference 

between irradiated patients and controls. In sexually active women, 

moderate to severe lack of vaginal lubrication was reported by 50% in the 

radiotherapy group, and by 23% in the control group (p=0.07). Thirty-two per 

cent of the irradiated, versus 13% of the non-irradiated women, were unable 

to achieve orgasm (p=0.15). Thirty-five per cent of the irradiated and 11% 

of the non-irradiated women that had been sexually active, had moderate to 

severe dyspareunia (p=0.04), and 35% versus 6%, respectively, had vaginal 

bleeding during intercourse (p=0.008). Fifty-five per cent of the irradiated and 

15% of the non-irradiated women experienced reduced vaginal dimension 

(p=0.004). There were no significant differences in mean scores of satisfaction 

with sex life between irradiated and non-irradiated women.The IIEF 

was returned from 281 men, 111 who had been irradiated, and 170 treated 

with surgery alone. Approximately 41% of the irradiated and 58% of the nonirradiated 

had been sexually active the last four weeks (p=0.007). The score 

of sexual desire was not significantly different in the two groups; irradiated 

patients had a mean score of 4.9 and the non-irradiated a score of 5.1, out of 

a maximum score of 10. The frequency of moderate to severe erectile dysfunction 

(score 16 or less of a total score of 30) was 87% in the radiotherapy 

group and 61% in the non-irradiated group (p< 0.001). Fourteen per cent 

of the irradiated, and 7% of the non-irradiated men had used treatment for 

erectile dysfunction (p=0.06). Irradiated patients had significantly impaired 

scores for several scales; orgasmic function (2.9 vs 4.6, maximum score 10, 

p=0.003), satisfaction with sexual intercourse (2.3 vs 4.4, maximum score 15, 

p=0.003), and overall satisfaction with sex life (4.2 vs 5.6, maximum score 10, 

p


and neck. A previous reported trial on intra-arterial chemoradiation versus 

intravenous chemoradiation was negative (ASTRO annual meeting 2006). 

Analysis on this and earlier studies revealed tumor volume and unilateral 

intra-arterial administration as a predictor for outcome. The purpose of this 

study was to reveal the category of patients that can benefit from unilateral 

cisplatin chemoradiation. 

Materials: 239 patients with (functionally) inoperable head and neck cancer 

were included from 2000 till 2004 in a multicenter randomized phase III trial 

comparing intra-arterial (4x150 mg/m2) and intravenous (3x100 mg/m2) cisplatin 

chemoradiation (70 Gy in 35 daily fractions). Subgroup analysis on 

primary site, tumor volume and uni versus bilateral intra-arterial infusion was 

performed. 

Results: Local control (LC) was significantly better in the intra-arterial vs. 

the intravenous arm among patients whose tumor did not extend across the 

midline (LC: HR=.17, 95% CI: .05-.60, p=.0025), while it was non-significantly 

worse for patients whose tumor did extend across the midline (LC: HR=1.43, 

95% CI: .66-3.09). Further evaluating the treatment effect by extension 

across the midline and tumor volume (T 30 ml, >30 ml) revealed that the 

benefit from intra-arterial treatment was limited to the 26 patients with a relatively 

large tumor not extending across the midline (LC: HR=.14, 95% CI: 

.03-.72, p=0.0547) while no significant benefit was observed in the remaining 

patients. Similar to local control disease specific survival was superior 

for patients with lateralized tumors treated with intra-arterial chemoradiation 

(Fig.1). 

Conclusions: For lateralized tumors with a volume of > 30 ml local control 

and disease specific survival was superior with intra-arterial cisplatin 

chemoradiation compared to intravenous chemoradiation. For all other categories 

intra-arterial was non-significantly worse. 

276 oral 

CONCOMITANT CHEMORADIOTHERAPY(CT/RT) 

VS NEODJUVANT CHEMOTHERAPY WITH DOC- 

ETAXEL/CISPLATIN/5FLUOROURACIL(TPF) FOLLOWED CT/RT IN 

LOCALLY ADVANCED HEAD AND NECK CANCER. FINAL RESULTS 

OF A PHASE II RANDOMIZED STUDY 

A. Buffoli 1 , L. Loreggian 2 , A. Gava 3 , F. Campostrini 4 , G. Gardani 5 , L. 

Tomio 6 , D. Dondi 7 , M. Polsinelli 1 , G. Morandini 8 , A. Paccagnella 9 

1 

AZIENDA OSP.UNIV. S.M. MISERICORDIA UDINE, Radiotherapy, Udine, 

Italy 

2 

AZIENDA OSPEDALIERA PADOVA IOV, Radiotherapy, Padova, Italy 

3 

OSPEDALE CA FONCELLO, Radiotherapy, Treviso, Italy 

4 

AZIENDA USSL 21, Radiotherapy, Legnago, Italy 

5 

OSPEDALE SAN GERARDO, Radiotherapy, Monza, Italy 

6 

OSPEDALE S.CHIARA, Radiotherapy, Trento, Italy 

7 

SANOFI AVENTIS, Medical Research, Milano, Italy 

8 

AZIENDA OSP.UNIV. S.M. MISERICORDIA UDINE, Oncology, Udine, Italy 

9 

OSPEDALE SS. GIOVANNI E PAOLO, Oncology, Venezia, Italy 

Purpose: Concomitant CT/RT is the standard treatment for locally advanced 

head and neck squamous cell carcinoma. This trial explores the efficacy of induction 

chemotherapy with TPF before concomitant CT/RT and concomitant 

CT/RT alone in locally advanced unresectable disease. 

Materials: From January 2003 to January 2006, 101 patients (pts) with stage 

III-IV M0, PS 0-1, were randomized to 2 cycles of cisplatin (P) 20mg/sqm 

days 1-4, 5FU (F) 800 mg/sqm 96-hour CI wks 1 and 6 during RT (66-70 Gy) 

(Arm A) or 3 cycles TPF (docetaxel 75 mg/sqm and P 80 mg/sqm on day 1, 

F 800 mg/sqm 96 hours CI) every 3 weeks followed by the same CT/RT (Arm 

B). Neck dissection was planned for pts with stage N2-N3 and pathological 

complete response (CR) at the primary tumor. A minimum accrual of 96 pts 

was required to detect a difference in radiological CR (primary endpoint) of at 

least 15% in favor of arm B. 

Results: Pts/tumor characteristics were well balanced in the two arms. During 

TPF, G3-4 neutropenia was the main hematological toxicity (52%) while 

nonhematological toxicities were mild. CR rate after TPF was 6.5%. During 

concomitant CT/RT, hematological and nonhematological toxicities were not 

increased in the experimental arm B and the feasibility of CT/RT was not compromised. 

Grade 3-4 toxicities in arms A and B, respectively, were mucositis 

S 89 

38% and 25%, dysphagia 21% and 16%, skin reaction 13% and 15%, weight 

loss 2% and 4%. Radiological evaluation (CT or MRI scan) of responses 6-8 

weeks from the end of CT/RT showed a CR of 21.2% in arm A and 50.0% in 

arm B. Radiological CRs at 8 months for unresected pts were 40.0% in Arm A 

and 57.1% in Arm B. Median OS and 1-yr OS were respectively 33.3 months 

and 77.6% in Arm A; median OS was not reached in arm B and 1-yr OS was 

86.0%. 

Conclusions: Neoadjuvant TPF is feasible and does not compromise subsequent 

concomitant CT/RT. Compared with CT/RT, induction TPF plus CT/RT 

significantly improves clinical CR evaluated at 8 weeks and 8 months after 

the end of the treatment. A trend for improved OS was also observed. The 

phase III part of the study with survival as the primary end-point is ongoing. 

277 oral 

IS THERE A DOSE-EFFECT RELATIONSHIP IN ELECTIVE NODAL 

IRRADIATION FOR SQUAMOUS CELL CARCINOMA OF THE HEAD 

AND NECK IN THE POSTOPERATIVE SETTING? 

M. R. Vergeer 1 , P. Doornaert 1 , R. de Bree 2 , R. Leemans 2 , B. Slotman 1 , 

H. Langendijk 3 

1 

VU UNIVERSITY MEDICAL CENTER, Radiation Oncology, Amsterdam, 

Netherlands 

2 

VU UNIVERSITY MEDICAL CENTER, Otolaryngology/Head and Neck 

Surgery, Amsterdam, Netherlands 

3 

UNIVERSITY MEDICAL CENTER GRONINGEN/UNIVERSITY OF GRONINGEN, 

Radiation Oncology, Groningen, Netherlands 

Purpose: This study was performed to investigate the presence of a doseeffect 

relationship in electively irradiated N0 necks and to identify prognostic 

factors for regional recurrence. 

Materials: This study included 619 patients with HNSCC, with either unilateral 

or bilateral cN0 and pN0 necks, who were treated between 1985 and 

2000 with primary surgery and postoperative radiotherapy. Of all 1238 necks, 

785 were treated with elective nodal irradiation in case of a cN0 or pN0 neck. 

Before 1997, the elective dose on the neck was 50 Gy (ED50Gy). From 1997 

on, the elective dose was decreased to 46 Gy (ED46Gy). 

Results: Regional control at 3 years was 94% in the cN0 neck compared to 

97% the pN0 neck and 90% in the ipsilateral compared to 96% the contralateral 

neck (p=0.08 and p= 0.006, respectively). Neck side was a prognostic 

factor for regional control in the cN0 neck, although not in the pN0 neck. Regional 

control at 3 years was 78% in the ipsilateral cN0 neck and 96% in 

the contralateral cN0 neck (p


Results: For all patients, the rate of SWALM6 was 23%. After univariate 

and multivariate logistic regression analysis, the following factors turned out 

to be independent prognostic factors for SWALM6: T3-T4, bilateral neck irradiation, 

weight loss prior to radiation, oropharyngeal and nasopharyngeal 

tumours, accelerated radiotherapy and concomitant chemoradiation. By summation 

of the regression coefficients derived from the multivariate model, the 

Total Risk Score (TRS) could be calculated. In the logistic regression model, 

the TRS was significantly associated with SWALM6 (OR: 1.19 per point (95% 

CI: 1.14-1.23; p


281 oral 

PHASE II STUDY OF PET IMAGE-GUIDED IMRT TO 60 GY 

P. Grigsby 1 , A. Singh 1 

1 MALLINCKRODT INSTITUTE OF RADIOLOGY, St Louis, USA 

Purpose: To evaluate the feasibility and toxicity of PET Image-Guided IMRT 

irradiation of FDG-PET positive pelvic and para-aortic lymph nodes to 60 Gy 

in patients with carcinoma of the cervix. 

Materials: This is a prospective Phase II study of 24 patients with FIGO 

clinical stages Ib2 to IIIb cervical cancer. The pre-treatment FDG-PET/CT 

demonstrated FDG-positive pelvic and para-aortic lymph nodes without evidence 

of other distant metastatic disease. Patients received external irradiation 

to the pelvis and para-aortic region, intracavitary brachytherapy, and 

concurrent chemotherapy with weekly cisplatin. Using IMRT over 30 fractions, 

50.4 Gy was delivered to the CTVNodal volume in the pelvis and para-aortic 

lymph node regions and 60 Gy was administered to the FDG-positive lymph 

nodes in the pelvis and para-aortic regions. Acute and late toxicity were evaluated 

and recorded weekly during therapy and with each follow-up according 

to the Common Toxicity Criteria scale. 

Results: All 24 patients received the prescribed 60 Gy IMRT to the positive 

pelvic and para-aortic lymph nodes. The median follow-up was 14.3 months 

(range 3-40). Acute grade 3 toxicity occurred in 58% (14/24), acute grade 4 

toxicity occurred in 33% (8/24), and one patient had grade 5 toxicity during 

treatment due to renal failure from chemotherapy. Three patients had late 

grade 4 toxicity consisting of small bowel obstruction in 2 and proctitis in one. 

There were no late grade 5 toxicities. The mean overall treatment time was 

58 days (range 45 to 101 days). Nineteen patients (19 of 24) underwent a 3month 

follow-up FDG-PET scan which demonstrated absence of FDG uptake 

in the pelvic and para-aortic lymph nodes in 17/19 (89%). The 36-month 

progression-free survival estimate for all patients was 23%. The 36-month 

progression-free survival estimate for the 17 patients with no FDG uptake in 

the 60 Gy volumes on their 3-month posttherapy FDG-PET was 25% with all 

recurrences occurring at distant sites (i.e., none failed in the pelvic or paraaortic 

lymph nodes). 

Conclusions: The results suggest that PET Image-Guided IMRT to 60 Gy 

to pelvic and para-aortic lymph nodes with concurrent chemotherapy results 

in elimination of nodal disease in most patients but survival is poor due to 

the development of distant metastatic disease. The grade 4 toxicity was high 

(33%, 8/24) and one patient died from complications of therapy. 

282 oral 

DOSE-VOLUME FOR IONIZING RADIATION TO THE RECTUM 

AND SIGMOID DECIDES THE PREVALENCE OF UNEXPECTED 

DEFECATION IN CLOTHING 

H. Lind 1 , G. Dunberger 1 , M. Al-Abany 2 , B. Lind 3 , E. Alevronta 4 , E. 

Onelöv 5 , J. Bohlin 6 , G. Steineck 7 , E. Åvall-Lundqvist 8 

1 

KAROLINSKA INSTITUTET, Department of Clinical Cancer Epidemiology, 


2 

KAROLINSKA INSTITUTET AND KAROLINSKA UNIVERSITY HOSPITAL, 

Oncology-Pathology, Clinical Cancer Epidemiology and Medical Radiation 


3 

KAROLINSKA INSTITUTET AND STOCKHOLM UNIVERSITY, Medical 

Radiation Physics, Stockholm, Sweden 

4 

KAROLINSKA INSTITUTET, Medical Radiation Physics and Medical Physics, 

Medical School of Patras, Stockholm, Sweden 

5 

KAROLINSKA INSTITUTET, Clinical Cancer Epidemiology, Stockholm, 

Sweden 

6 

KAROLINSKA UNIVERSITY HOSPITAL, Diagnostic Radiology, Stockholm, 

Sweden 

7 

KAROLINSKA INSTITUTET AND SAHLGRENSKA ACADEMY, Oncology- 

Pathology, Clinical Cancer Epidemiology, Stockholm and Gothenburg, 

Sweden 

8 

KAROLINSKA UNIVERSITY HOSPITAL, Gynecological Oncology, Stockholm, 

Sweden 

Purpose: The relation between dose-volume histograms of ionizing radiation 

and the prevalence of patient-reported radiotherapy-induced symptoms 

among long term gynecological cancer survivors is unknown. 

Materials: Six hundred and seventy-seven women, who were treated with radiotherapy 

for a gynecological cancer in Stockholm during 1991 to 2003, participated 

in this population-based study. A control group of 480 women from 

the Swedish Population Registry, matched for age and regional residence, 

was also included. Based on in-depth interviews a questionnaire including 

351 questions was constructed, and validated face-to-face. The questionnaire 

covered symptoms from six anatomical regions as well as demographical, 

psychological and quality of life issues. In addition, the medical records 

were reviewed for information concerning treatment details. Treatment-plan 

data were restored, risk organs i.e. anal sphincter, rectum, sigmoid and small 

intestines contoured and the corresponding dose-volume histograms calculated. 

Mean dose from organ volumes were correlated to the prevalence of 

radiotherapy-related symptoms. 

Results: Response rate was 77 % for cancer survivors and 72 % for control 

S 91 

women. Mean follow-up time was 7.8 years. Dose-volume histograms were 

calculated for 85 % of the responding patients. An unexpected defecation 

in clothing, during the last 6 months, affected 18 % of survivors after pelvic 

radiotherapy and 0.9 % of controls, Relative Risk (RR) 20.9 with a 95 % CI 

6.0-72.2. The risk of having the symptom was significantly correlated to the 

mean dose of ionizing radiation to the rectum and the sigmoid. The RR for 

unexpected defecation in clothing with a mean dose of ≥ 40 Gy to the rectum 

and the sigmoid compared to patients receiving


model, the median D100 and D90 were 54.4 Gyα/β10 and 63.5 Gyα/β10 for 

the IR-CTV, respectively and 61.6Gyα/β10 and 74.9 Gyα/β10 for the HR- 

CTV, respectively. Twenty-three patients developed grade 1-2 complications. 

One patient presented grade 3 ureterovaginal fistula. No grade 4 or greater 

complication was observed. 

Conclusions: MRI-guided PDR BT with optimization integrating limits of tolerance 

to organs at risk allows excellent local control rates. Moreover, our 

results confirm that the ability to optimized dwell times may contribute to an 

improvement in local control rates with a low rate of late complications. 

285 oral 

THE ROLE OF HYPERTHERMIA IN THE TREATMENT OF LOCALLY 

ADVANCED CERVIX CARCINOMA WITH RADIOTHERAPY: A 

SYSTEMATIC REVIEW. PRELIMINARY RESULTS ON BEHALF OF 

THE COCHRANE GYNAECOLOGICAL CANCER REVIEW GROUP. 

L. Lutgens 1 , C. van der Zee 2 , D. De Haas-Kock 1 , J. Buijsen 1 , G. van 

Mastrigt 1 , G. Lammering 1 , M. Pijls-Johannesma 1 , D. De Ruysscher 1 , P. 

Lambin 1 

1 MAASTRO CLINIC, Radiotherapy, Maastricht, Netherlands 

2 ERASMUS MC, Radiation Oncology, Rotterdam, Netherlands 

Purpose: To assess whether combined radiotherapy and hyperthermia 

(RHT) yields an advantage as compared to standard radiotherapy only (RT) 

for the treatment of locally advanced cervix carcinoma. The endpoints studied 

were (1) local tumor control, (2) overall survival (OS) and disease free 

survival (DFS) and (3) treatment related acute and late toxicity grade ≥ 3. 

Materials: Randomized controlled trials (RCT) were identified by searching 

the Cochrane Central Register of Controlled Trials (CENTRAL), MED- 

LINE (1975 to present), EMBASE (1975 to present) and CANCERLIT (1975 

to present). In addition the trial registers of Physicians Data Query Protocols 

(Open and Closed Protocols), United Kingdom Co-ordinating Committee 

on Cancer Research (UKCCCR), Register of Cancer Trials (Open and 

Closed Protocols) and MetaRegister were searched for open and closed trials. 

Searches were performed without restricting the language of studies 

retrieved. For statistical analysis a weighted estimate of the typical treatment 

effect across studies was computed for 2- and 3-year survival data. The risk 

ratio (RR) was used as the effect measure. Chi-square heterogeneity tests 

were used to test for statistical heterogeneity among trials. The analyses 

were performed using random or fixed effects models. Statistical analysis 

was performed with Reference Manager (RevMan). 

Results: Six RCTs published between 1987 and 2005 were identified and 

used for the current analysis. Between 70 and 100% of patients included in 

5 studies showing a beneficial effect of hyperthermia had FIGO stage IIIB 

disease in contrast to 38% of patients in the only negative study. The pooled 

data yielded a significantly higher complete response rate following RHT (RR 

1.38; 95% CI 1.15 - 1.65; p


288 oral 

RADIATION-INDUCED LATE FUNCTIONAL AND FIBROTIC 

CHANGES IN MOUSE URINARY BLADDER: IS THERE A ROLE OF 

HYPOXIA? 

J. Jaal 1 , W. Dörr 2 

1 TARTU UNIVERSITY CLINICS, CLINIC OF HAEMATOLOGY AND ONCOLOGY, 

Dept. of Radiotherapy and Oncological Therapy, Tartu, Estonia 

2 UNIVERSITY OF TECHNOLOGY, MEDICAL FACULTY CARL GUSTAV CARUS, 

Laboratory of Radiobiology and Experimental Centre, Dresden, Germany 

Purpose: Bladder dysfunction, due to radiotherapy of pelvic tumours, occurs 

in three phases: an early, reversible reaction, a dose-dependent, symptomfree 

latent time, and a late response phase with irreversible and progressive 

changes. During the late phase, changes in collagen metabolism and development 

of fibrosis have been demonstrated. Whether formation of fibrotic 

tissue after irradiation is accompanied by tissue hypoxia was evaluated in the 

present study. 

Materials: Female C3H mice were subjected to single dose irradiation with 

26 Gy. Groups of mice (n=8) were sacrificed between days 60 to 330 after 

irradiation. Before sacrifice, the functional bladder damage of each animal 

was evaluated from urination frequency assay. Therefore, all histological parameters 

could be correlated with bladder function on individual basis. An 

age-matched, untreated control group (n=8) was included at each time point. 

The bladders were excised, fixed in formalin and processed for histology and 

immunohistochemistry. The amount of collagen in the bladder wall was determined 

after Massons Trichrome staining using an arbitrary score ranging from 

0 to 3. Also, the number of Hypoxia-inducible factor 1- alpha (HIF-1alpha) 

positive cells in the bladder wall was counted in 5 randomly taken microscopic 

fields. 

Results: Compared to age-matched controls, irradiated animals displayed increased 

levels of urination frequency (0.24b0.01 vs 0.38b0.04, meanbSEM, 

n=80) and collagen (1.20b0.01 vs 1.81b0.07, meanbSEM, n=80). Moreover, 

the number of infiltrating HIF-1alpha positive cells in the urinary bladder wall 

was higher in irradiated animals (0.35b0.01 vs 3.34b0.62, meanbSEM, n=80). 

In individual irradiated animals, the frequency of urination was positively correlated 

with the amount of collagen in the bladder wall (p< 0.0001). Similarly, 

animals with increased urination frequency had increased levels of HIF-1 alpha 

positive cells in the bladder wall (p< 0.0001). Additionally, the amount 

of collagen was positively correlated with the number of HIF-1alpha positive 

cells on individual basis (p< 0.0001). 

Conclusions: Irradiation results in late functional and fibrotic damage of 

mouse urinary bladder. Moreover, irradiation increased the number of infiltrating 

HIF-1alpha positive cells in the bladder wall. Taken together, these data 

illustrate that hypoxia might play a role in the development of late radiationinduced 

fibrosis in the urinary bladder. 

289 oral 

MEDIUM-SIZED ARTERIES DEVELOP A THICKER NEO-INTIMA 

FOLLOWING IRRADIATION 

N. Russell 1 , S. Hoving 2 , L. Woerdeman 3 , J. Hage 3 , S. Heeneman 4 , R. 

de Bree 5 , P. Lohuis 6 , L. Smeele 6 , M. Deamen 4 , F. Stewart 2 

1 

NKI-AVL, Radiotherapy, Amsterdam, Netherlands 

2 

NKI-AVL, Department of Experimental Therapy, Amsterdam, Netherlands 

3 

NKI-AVL, Department of Plastic and Reconstructive Surgery, Amsterdam, 

Netherlands 

4 

UMCM, Cardiovascular Research Institute, Maastricht, Netherlands 

5 

VUMC, Department of Head and Neck, Amsterdam, Netherlands 

6 

NKI-AVL, Department of Head and Neck, Amsterdam, Netherlands 

S 93 

Purpose: Vascular damage is an important determinant of late radiation morbidity. 

This study evaluates the nature of pathogenic changes occurring in 

medium-sized arteries following radiotherapy for head and neck cancer (H&N) 

and breast cancer (BC). 

Materials: Biopsies of arteries used for anastomosis in free-flap reconstructive 

surgery were obtained from 114 patients. We biopsied the facial artery 

from 25 irradiated and 45 unirradiated H&N patients. Internal mammary 

artery (IMA) biopsies were obtained from 19 BC patients irradiated to the 

internal mammary chain and from 25 unirradiated patients. The free flap 

artery from each patient was also biopsied. Clinical and therapeutic data were 

recorded. Measurements were made of histological parameters of paraffin 

embedded vessels: using imaging analysis software the ratio of the thickness 

of the intima to the thickness of the media (IMT), a marker of atherosclerotic 

plaque development, was determined. The sections were also scored for 

proteoglycan content and collagen content. 

Results: Mean follow-up time was 4 years following irradiation. There was 

a significant 1.7-fold increase in the IMT following radiotherapy in the H&N 

patient group (p=0.031), and a 1.5-fold increase in the BC group, after correction 

for the IMT value of the free flap artery. There was an increase in the 

proteoglycan content of the media in the irradiated IMA vessels, from 59.9% 

to 69.8% (p=0.005). 

Conclusions: Pathological changes were observed and quantified in irradiated 

vessels from both patient groups, but absolute values for IMT were 

greater in the H&N group. These results suggest radiotherapy is an additional 

risk factor for atherosclerosis. 

290 oral 

PHARMACOLOGICAL MODULATION OF THE RHO/ROCK PATHWAY 

REVERSES LUNG FIBROSIS IN C57B6 MICE 

N. Pasinetti 1 , L. Costa 1 , P. Opolon 2 , D. Violot 3 , S. Magrini 1 , J. Bourhis 3 , 

M. C. Vozenin-Brotons 4 

1 ISTITUTO DEL RADIO, Radiotherapy, Brescia, Italy 

2 INSTITUT GUSTAVE ROUSSY, UMR 8121 Laboratoire de vectorologie et 

transfert de gènes, Villejuif, France 

3 INSTITUT GUSTAVE ROUSSY, Laboratoire UPRES EA 27-10 Radiosensibilité 

des tumeurs et tissus sains, Villejuif, France 

4 LRPAT, IRSN/DRPH/SRBE, Radiobiology, Fontenay aux Roses, France 

Purpose: Activation of Rho/ROCK signalling pathway triggers radio-induced 

fibrosis in the gut and constitutes a new therapeutic target as Rho inhibition 

using statins displays anti-fibrotic properties in radiation enteropathy models. 

In the present study we aimed at investigating whether the pathological activation 

of the Rho/ROCK pathway was specific to the gut or could constitute 

a more general pathogenic path. Therefore, we developed models of lung fibrosis 

in mice and used them to test the anti-fibrotic properties of Rho/ROCK 

pharmacological inhibitors. 

Materials: Lung fibrosis was induced in pathogen-free 10-wk-old female 

C57BL/6 mice by 1) IP injection of the radio-mimetic drug Bleomycin at 40 

mg/kg body weight on Days 0, 2, 4, 6 and 8 and 2) Thorax irradiation (16 

Gy, 17 Gy; RX 250 KeV). Mice follow-up was performed twice a week for 

the overall experimental period and tissue collection was perfomed at Day 

15, Day 30 for the bleomycin model and at week 15 and 26 in the irradiation 

model. Fibrosis development was monitored by HES staining. Safron stain 

was used for collagen quantification after slide scanning (Nikon Scan) and 

analysis by Pixcyt program. CTGF and α SM actin expression were studied 

by Western Blot and Q-RT-PCR. Curative effect of Rho and ROCK inhibition 

were studied in vivo using respectively pravastatin (40 mg/Kg/d), simvastatin 

(20 mg/Kg/d) and Y-27632 (30 mg/Kg/d) delivered over 14 days via osmotic 

pump implantation. 

Results: Histopathological examinations essentially show inflammatory lesions 

mixed up with fibrotic areas at Day 15 whereas fibrosis is fully established 

D30. The fibrotic lesions are located in the subpleural zones and within 

the large peripheral vessels. Quantification of the collagen deposition show 

progressive increase of collagen after D15. Curative administration of pravastatin 

and Y-27632 increased the body weight of the animals by 25% as compared 

to the vehicle-treated group and significantly improved survival (83% vs 

56%), whereas Simvastatin was less potent with a survival gain equal to 10%. 

In the pravastatin and Y-27632 -treated groups HES analysis showed an almost 

complete regression of fibrosis in all animals whereas results obtained 

with simvastatin were less impressive. Similar experiments are currently ongoing 

in the radiation-induced model. 

Conclusions: The present results show that bleomycin-induced lung fibrosis 

can be modulated by Rho/ROCK pathway inhibition and suggest different 

mechanism of action for pravastatin vs simvastatin. As the Rho family is 

composed of several members, one hypothesis is that the two drugs target 

different member of the Rho family. Our previous studies suggest involvement 

of RhoA and B and the current anti-fibrotic action displayed by Y-27632 

supports RhoA involvement. Further studies are currently ongoing to define 

the Rho proteins involved along with the Guanine-exchange factors (GEF) 

associated. In conclusion, this study confirms and extends the therapeutic 

potential for Rho/ROCK inhibition to modulate fibrosis induced by radio- and 

chemo-therapy.


291 oral 

ACUTE EPITHELIAL EFFECTS OF RADIOTHERAPY ARE CAUSED 

BY PERSISTENT CHECKPOINT ACTIVATION RATHER THAN 

CELL-KILL 

I. Turesson 1 , J. Nyman 2 , M. Simonsson 3 , F. Qvarnström 3 , M. Book 1 , I. 

Hermansson 2 , S. Sigurdardottir 1 , K. A. Johansson 4 

1 

UPPSALA UNIVERSITY, Department of Oncology, Radiology and Clinical 

Immunology, Uppsala, Sweden 

2 

GÖTEBORG UNIVERSITY, SAHLGRENSKA UNIVERSITY HOSPITAL, Department 

of Oncology, Gothenburg, Sweden 

3 

UPPSALA UNIVERSITY, Uppsala, Sweden 

4 


of Radiophysics , Gothenburg, Sweden 

Purpose: In response to ionizing radiation, cells activate DNA damage 

checkpoint pathways to protect the genome. The outcome of the DNA damage 

checkpoint activation by radiation depends largely on the cell type in 

various tissues and radiation dose. Damaged cells can be eliminated by cell 

death, or permanent arrest induced by cellular senescence or terminal differentiation. 

Alternatively, cells can survive and resume cell cycle progression 

upon checkpoint recovery. The aim of this study was to estimate the impact 

of DNA damage checkpoints on the keratinocyte response to fractionated radiotherapy. 

Materials: Skin punch biopsies from breast cancer patients were taken before, 

during and after radiotherapy, from areas receiving daily fractions of 2 

Gy over the course of 5 weeks. Cell cycle progression in the basal cell layer 

of the epidermis was determined by staining for the molecular markers: Ki- 

67, Rb, cyclin A, cyclin B, phosphoH3 and p21. Cell death was quantified by 

γH2AX staining. Clonogenic stem cells were distinguished from clonogenic 

progenitor cells by BMI-1 staining. The number of stained keratinocytes in 

the basal cell layer were counted. 

Results: Our data suggests an immediate G0 arrest upon commencement 

of treatment. However, after 2 to 3 weeks cells appear to re-enter into the 

cell cycle, displaying an effort to repopulate the epidermis. Nevertheless, 

from this time point and onwards, cell cycle arrests in G1 and G2 increased 

gradually and, accordingly, entry into mitosis was depressed. Cell death was 

infrequent throughout the treatment and no reduction of stem cells was evident. 

Checkpoint recovery and accelerated repopulation was only detected 

after completion of radiotherapy. 

Conclusions: In normal epithelium, such as skin, repeated DNA damage 

induced by fractionated radiotherapy result in persistent checkpoint activation 

causing a permanent growth arrest of clonogenic non-stem cells. Our results 

indicate that the observed growth arrest, rather than cell-killing, causes the 

acute effects. Furthermore, clonogenic stem cells are radioresistant, and 

their ability to fully recover the epithelium is not compromised by the effects 

of radiotherapy. 

Clinical aspects of hadron therapy 

292 oral 

EFFECTIVENESS AND SAFETY OF SPOT SCANNING PROTON 

RADIATION THERAPY FOR SKULL BASE TUMORS: FIRST LONG 

TERM REPORT OF THE PSI EXPERIENCE 

C. Ares 1 , A. Lomax 1 , E. B. Hug 1 , A. Bolsi 1 , B. Timmermann 1 , H. P. Rutz 

1 , A. Coray 1 , E. Pedroni S 1 , G. Goitein 1 

1 PAUL SCHERRER INSTITUTE, Center for Proton Radiation Therapy, Villigen 

- PSI, Switzerland 

Purpose: To evaluate the effectiveness and safety of spot scanning proton 

radiation therapy in chordomas and low- and intermediate-grade chondrosarcomas 

of the skull base. 

Materials: Between October 1998 and November 2005, 64 patients with 

chordomas (42 patients) and low- or intermediate-grade chondrosarcomas 

(22 patients) of the skull base have been treated at Paul Scherrer Institute with 

proton radiation therapy using the spot scanning technique with the scanning 

gantry, developed at PSI, and degraded beams of the 590-MeV cyclotron. 

All patients had gross residual tumor at the time of treatment. Median total 

dose for chordomas was 73.8 Gy (RBE) (range, 67.674 Gy (RBE)) and 68.4 

Gy (RBE) (range 63-74 Gy (RBE)) for chondrosarcomas. Radiotherapy was 

delivered with standard fractionation at 4 fractions per week. Local control, 

disease specific survival and overall survival rates were calculated using the 

Kaplan-Meier method. Toxicity was assessed according to the Common Terminology 

Criteria (CTCAE v.3.0). 

Results: Mean follow-up time was 38 months with a minimum follow-up period 

of > 1 year (range, 1492 months). Five patients with chordoma and 1 

patient with chondrosarcoma experienced local recurrence after proton radiation 

therapy. No regional failures or distant metastasis were observed. 

The actuarial 5-year local control rates were 81% and 94% for chordomas 

and chondrosarcomas, respectively. Brainstem compression of the tumor 

at the time of proton radiation therapy (p=0.007) and gross tumor volume 

>25ml (p=0.03) were statistically significantly associated with lower local control 

rates. Rates of disease specific survival and overall survival at 5 years 

were 81% and 62% for chordomas and 100% and 91 % for chondrosarcomas, 

respectively. High grade late toxicity consisted of 1 patient with Grade 3 

and 1 patient with Grade 4 unilateral optic nerve neuropathy, and 2 patients 

with Grade 3 temporal lobe CNS necrosis. No patient experienced brainstem 

toxicity. The actuarial 5-year freedom from high grade toxicity was 94%. Due 

to the small number of events no risk factors predictive of high grade toxicity 

were identified. 

Conclusions: Our data indicate safety and efficacy of Spot-Scanning based 

Proton-Radiotherapy for skull base chordomas and chondrosarcomas. With 

target definition, dose prescription and normal organ tolerance levels comparable 

between active scanning technology at PSI and passive scattering 

based proton-radiotherapy of other institutions rates of complication-free survival, 

tumor control and overall survival are at present similar. Risk factors for 

local failure are similar to other proton therapy based series (brainstem compression, 

residual gross tumor volume >25ml). We have established outcome 

data for a cohort of patients treated homogeneously, that will be the basis for 

introducing new technologies and for developing new treatment algorithms. 

293 oral 

SENSITIVITY TO ORGAN MOVEMENT OF PROSTATE IMPT AND 

IMRT 

M. Soukup 1 , M. Soehn 1 , J. Liang 2 , D. Yan 2 , M. Alber 3 

1 

UNIVERSITY HOSPITAL TUEBINGEN, Section for biomedical physics, 

Tuebingen, Germany 

2 

WILLIAM BEAUMONT HOSPITAL, Radiation Oncology, Royal Oak MI, USA 

3 

UNIVERSITY HOSPITAL TUEBINGEN, Section for Biomedical Physics, 


Purpose: Intensity modulated therapy with photons (IMRT) and protons 

(IMPT) allows for high dose conformality to the PTV and sparing of the OARs 

if calculated on a single static CT. For prostate patients organ movement with 

related changes of the density distribution in the irradiated volume occurs 

during the irradiation course. We evaluated the sensitivity of IMPT and IMRT 

plans to organ movement by recalculation of the delivered dose and accumulation 

after warping the dose to the reference geometry. 

Materials: IMPT and IMRT treatment plans were evaluated for 4 patients with 

an average of 16 CT data sets per patient. The treatment plans are calculated 

on one CT data set and recalculated on the CTs taken during the irradiation 

course. The PTV is prescribed to 78Gy and created as a hull of the prostate 

contours from the first three CTs surrounded by a margin of 7mm. All CTs are 

matched to the bony structures around the prostate. Thus the patient setup 

corrections (shifts, rotations) to reach the optimum position of the planning CT 

are simulated. To estimate the influence of gas volumes in rectum, another 

set of treatment plans was created with simulated filling of the rectum cavities 

with water. Both IMPT and IMRT were optimized with the same EUD-based 

optimization algorithm. To evaluate the dose to organs correctly, the dose is 

accumulated in the reference geometry by a deformable organ registration 

algorithm for the total DVH and EUD. Accurate dose calculation algorithms 

were used - Monte Carlo for IMRT and a pencil beam algorithm with the lateral 

heterogeneity correction and large angle scatter lateral correction for IMPT. 

Results: Similar plan quality can be achieved for both IMPT and IMRT on 

the original CT. Integral dose and dose to distant parts of the critical organs 

is significantly lower for IMPT. With IMPT unacceptably low total doses in the 

GTV were observed for patients with gas in the rectum. Simulated filling of 

the cavities with water in the original CT helps to achieve similar total EUDs 

as with IMRT. The spread of the daily EUD is higher for IMPT, especially for 

the prostate and the rectum wall. The spread remains higher even with the 

gas cavities in all CTs filled with water. Thus, also other geometry changes 

than rectum filling play a role in the IMPT dose degradation. 

Conclusions: IMPT shows significantly higher sensitivity to organ movements 

than IMRT. Not taking care of the gas cavities can lead to serious 

underdosage of the target. 

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PROTON BEAM RADIATION THERAPY (PT) OF CHILDHOOD 

MALIGNANCIES AT THE PAUL SCHERRER INSTITUTE (PSI): A 

PROSPECTIVE ANALYSIS. 

B. Timmermann 1 , S. Maier 1 , A. Lomax 1 , E. Hug 1 

1 PAUL SCHERRER INSTITUTE, Villigen - PSI, Switzerland 

Purpose: Proton Beam Radiation Therapy is increasingly applied in the treatment 

of children with cancer. Still, clinical data on PT in children is limited. At 

PSI, any proton beam treatment in children is continuously and standardized 

followed up since 2004. We are now reporting on the first results regarding 

toxicity and tumour control. 

Materials: Since 2004, 51 children received PT at PSI. In total; 29 boys and 

22 girls have been treated with 0.3-19.5 age of years (med. 2.7) at time of 

first diagnosis. The most frequent diagnosis was sarcoma (in 23), beside 

brain tumour (in 19), chordoma or low grade chondrosarcoma (in 6) and var-


ious types (in 3). The tumour was located at head or neck in 41 children, at 

the spine in 8, and in the pelvis in 2 patients. In the majority of paediatric patients, 

gross residual disease was still present before PT started. All but one 

child had localized disease. One child presented with cervical lymph node 

metastases. In 40 children chemotherapy was administered before or during 

PT. In 48 out of 51 children, the full course of irradiation was performed with 

proton beam only. The median total dose for the group was 54 Gy (range, 

45-74.1 Gy) with 1.8.-2 Gy per fraction, 4-5 times weekly. Acute toxicity was 

registered weekly and classified according to the EORTC/RTOG scores. Additionally, 

questionnaires were sent out to referring clinicians and parents to 

evaluate long term side effects and tumour control. 

Results: After median follow-up time of 23 months (range, 5-61.5 months), 

5 children have died (9.8%). In 44 out of 51 children, local tumour control 

was achieved (86.3%). The predominant site of failure was the local tumour 

site. After failure analysis, only in-field recurrences have occurred. Seventeen 

children receiving parallel chemotherapy presented with acute toxicity 

scored grade 3-4 for bone marrow (n=15) or mucosa (n=2). In 35 children, information 

about long term toxicity was evaluable. We observed complications 

scored grade 1-2 for skin, salivary glands, eye, ear, bone/teeth, endocrine 

function or CNS. 

Conclusions: In our cohort, PT was feasible and well tolerated for the majority 

of the patients. No unexpected complication occurred. Local tumour 

control rates are promising. However, larger cohorts and longer follow-up 

time is needed to confirm first results. 

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CANCER RISK FROM NEUTRON DOSE IN PROTON THERAPY FOR 

ADULT AND PEDIATRIC PATIENTS 

C. Zacharatou Jarlskog 1 , H. Paganetti 2 

1 COPENHAGEN UNIVERSITY HOSPITAL, RIGSHOSPITALET, Department of 


2 MASSACHUSETTS GENERAL HOSPITAL AND HARVARD MEDICAL SCHOOL, 


Purpose: Due to the rising concern for radiation-induced cancers from scattered 

dose in proton treatments, a study was performed to estimate the dependence 

of secondary cancer risk on patient age and field parameters. Special 

emphasis was put on pediatric patients due to their long life expectancy 

after treatment and because their still developing tissues are more sensitive 

to radiation. 

Materials: One adult and five pediatric whole-body voxel phantoms were implemented 

in the Geant4 Monte Carlo as virtual patients. The adult phantom 

represented the anatomy of a 39-year old male while the pediatric models 

imitated a 9-month old male, a 4-year old female, an 8-year old female, an 

11-year old male and a 14-year old male. Eight proton treatment fields were 

simulated using a complete model of the nozzle at one of the treatment rooms 

of the F. H. Burr Proton Therapy Center at Massachusetts General Hospital. 

We used the simulated organ equivalent neutron doses and applied the BEIR 

VII models to estimate the lifetime attributable risk, LAR, for leukemia and 10 

solid cancers (stomach, colon, liver, lung, breast, bladder, thyroid, esophagus, 

pancreas and kidney) as a function of patient age, field characteristics 

and neutron origin. In order to disentangle the age- and gender-dependence 

of our phantoms, we also analyzed the risks for the 4-year old female assuming 

LAR model parameters for males. All LAR values were calculated for a 

prescribed dose of 70 Gy. 

Results: Overall, females are at a greater risk than males by a factor ~2.5. 

Neutrons generated in the nozzle give LAR values which are a factor ~10 

higher than those due to neutrons generated internally in the patient. Varying 

the beam range/modulation width from 10/5 cm to 15/10 cm increases 

the LAR by ~2. The lifetime cancer risk increases markedly as the patient 

age decreases, roughly a factor 10 between the 9-month old and the adult 

phantom. In female patients, the risk for breast cancer prevails but is still 

less than the baseline risk, which is however not the case for thyroid cancer. 

For male pediatric patients, the highest LAR values were found for lung cancer, 

leukemia and thyroid cancer. Leukemia had the highest risk for an adult 

male. The treatment LAR values were in general below 1%, except for breast, 

thyroid and lung cancer for females (up to 5%). 

Conclusions: Patient age and gender are of primary importance in estimating 

cancer risks in proton therapy. Overall, we found that the neutron-dose 

risk is low but can potentially exceed the baseline risk in the treatment of large 

tumors. 

296 oral 

INTENSITY MODULATED PROTON THERAPY VS HELICOIDAL 

TOMOTHERAPY IN NASOPHARYNX CANCER: NTCP EVALUATION 

L. Widesott 1 , A. Pierelli 2 , C. Fiorino 2 , I. Dell’Oca 3 , S. Broggi 2 , M. 

Cattaneo 2 , N. Di Muzio 3 , F. Fazio 4 , R. Calandrino 2 , M. Schwarz 1 

1 AGENZIA PROVINCIALE PER LA PROTONTERAPIA, Trento, Italy 

2 H.S. RAFFAELE, Department of Medical Physics, Milano, Italy 

3 H.S. RAFFAELE, Department of Radiotherapy, Milano, Italy 

4 H.S. RAFFAELE, Department of Radiotherapy and IBFM-CNR, Milano, Italy 

S 95 

Purpose: To compare intensity modulated proton therapy (IMPT) and Helical 

Tomotherapy (HT) treatment plans for nasopharynx cancer using a simultaneous 

integrated boost (SIB) approach. To have an evaluation of the probable 

clinical impact on OARs of the different dose distributon obtained, a detailed 

NTCP analysis is presented. 

Materials: Data of six patients previously treated with HT were used. A 

3-beams IMPT technique was optimized in the Hyperion TPS, simulating a 

’beam scanning’ technique. HT was planned in the Tomotherapy TPS. Both 

techniques were optimized to simultaneously deliver 66 Gy in 30 fractions on 

PTV1 (T+N+) and 54 Gy on PTV2 (N). NTCP calculation was performed for 

parotid glands and larynx using several sets of paramters (m, n, TD50) extracted 

from literature (Emami et al. 1991, Eisbruch et al. 1999, Roesink et al. 

2001, 2004, for the parotids and Rancati et al 2007 for the larynx). Furthermore 

we tried to evaluate, implementing the linear spline model proposed by 

Li et al. 2007, the mean stimulated and unstimulated saliva flow rate changes, 

24 months after radiation therapy compared to baseline. 

Results: Very similar PTVs coverage and homogeneity of the target dose distribution 

for IMPT and HT were found. The conformity index was significantly 

lower for protons compared to photons (1.19 vs 1.42 respectively). Mean 

dose in the omolateral and contralateral parotids decreased by 6.4 Gy and 

5.6 Gy respectively with IMPT. The values of V20 and V30 of mucosae and 

esophagus with IMPT were significantly lower in comparison with HT. Maximum 

dose of brain stem was reduced from 50.4 Gy (HT) to 35.0 Gy (IMPT). 

The average value of V50 for larynx was significantly lower in HT, while for 

thyroid was comparable. V30, V20 and V10 values in total body volume decreased 

with IMPT by 14.5%, 19.4% and 23.1% respectively. NTCP values 

for the parotids were significantly lower in IMPT for all the sets of parameters 

(p < 0.03), but we evaluated an almost full recovery of the contralateral parotid 

with HT too. Larynx NTCP was not statistically different for the two irradiation 

techniques (Table). 

Conclusions: Excellent target coverage, homogeneity within PTV’s and 

sparing of the OAR’s were reached with both modalities. IMPT allows better 

sparing for most OARs, at medium-to-low doses and it was highlighted in 

the NTCP evaluation of the parotids. Significantly lower integral dose in IMPT 

many have an important impact in decreasing radiation-induced cancers. 

297 oral 

INTERNATIONAL, MULTICENTRIC IN SILICO CLINICAL TRIAL 

IN LUNG, PROSTATE AND HEAD&NECK CANCER, COMPARING 

PHOTONS, PROTONS AND C-ION THERAPY TREATMENT: A 

MULTICENTRIC PLANNING STUDY BASED ON A REFERENCE 

DATASET OF PATIENTS: EVALUATION OF FEASIBILITY 

R. Jongen 1 , A. Dekker 1 , S. Qamhiyeh 2 , B. Baumert 1 , W. De Neve 3 , G. 

De Meerleer 3 , D. De Ruysscher 1 , M. Eble 4 , M. Engelsman 5 , V. Fonteyne 

3 , J. L. Habrand 6 , N. Kanematsu 7 , H. Langendijk 8 , A. Lomax 9 , I. Madani 

3 , B. Masayuki 7 , N. Matsufuji 7 , A. Mazal 6 , U. Oelfke 2 , W. Schlegel 2 , 

H. Tsujii 7 , M. Verheij 10 , C. Rasch 10 , T. van de Water 8 , P. Lambin 1 , M.


Pijls-Johannesma 1 

1 

MAASTRICHT RADIATION ONCOLOGY (MAASTRO), GROW, UNIVERSITY 

HOSPITAL MAASTRICHT, Radiation Oncology, Maastricht, Netherlands 

2 

DEUTSCHE KREBSFORSCHUNGSZENTRUM (DKFZ), Radiation Oncology, 


3 

UNIVERSITY HOSPITAL GHENT (UHG), Radiation Oncology, Ghent, 

Belgium 

4 

UNIVERSITY HOSPITAL AACHEN (KLINIKUM), Radiation Oncology, Aachen, 

Germany 

5 

MASSACHUSETTS GENERAL HOSPITAL AND HARVARD MEDICAL SCHOOL, 

Radiation Oncology, Boston, USA 

6 

CENTRE DE PROTONTHERAPIE D’ORSAY (CPO), Radiation Oncology, 

Orsay, France 

7 

NATIONAL INSTITUTE OF RADIOLOGICAL SCIENCES (NIRS), Radiation 

Oncology, Chiba, Japan 

8 

UNIVERSITY MEDICAL CENTER GRONINGEN (UMCG), Radiation Oncology, 


9 

PAUL SCHERRER INSTITUTE (PSI), Proton Radiotherapy, Villingen, 

Switzerland 

10 

NETHERLANDS CANCER INSTITUTE (NKI), Radiation Oncology, Amster- 

dam, Netherlands 

Purpose: Introducing the "In silico trial" and discussing issues related to initiating 

an international research study in the field of treatment planning comparisons. 

The aim of the trial is to demonstrate that, with the same dose on 

the tumor, particle therapy decreases irradiation of normal tissue in head and 

neck, prostate and lung cancer tumors, and therefore decreases the risk of 

both side effects in the surrounding normal tissues and of secondary tumor 

induction. In a subsequent study, we will investigate how these risk reductions 

translate into costs. Next, we will investigate if particle therapy increases tumor 

control probability as compared to photons, with the same probability of 

toxicity for normal tissue, resulting in improvements in local control and survival 

rate. 

Materials: In the first phase of the project, photon, proton and 12C-ions curative 

radiotherapy plans are compared using the same "state of the art" images 

and structure delineations, dose specifications, dose constraints and 

fractionation schedules. To prevent for patient selection, patients are consecutive 

included in this trial. Treatment plans are compared based on NTCP of 

OAR. Currently available RBE models will be used to estimate the biological 

effective dose. Each patient is its own reference case. The challenges to initiate 

the project were both scientific and management related. Scientifically, 

high credibility of the study is insured by including centers with longstanding 

experience in particle and/or photon radiotherapy. 

Results: Participants agreed on criteria for interpretation of motion and 

NTCP models used for comparison. Management issues were: data export 

and import, access to the data (security issues), compatibility of different 

treatment planning systems used by the centers, authorship rights, defining 

the tasks to the participants (resources) and finally management of information 

flow and evaluation of the work flow. Most of the above issues were 

settled by agreeing on a project protocol which describes the patient data, 

defines the criteria for treatment planning and sets the tasks to the participants. 

A secured FTP site has been launched for data transfer. Twice yearly 

review meetings will be held to ensure project progress, to discuss preliminary 

results and to implement new insights regarding patient selection and 

data analysis. 

Conclusions: The international, multi-centric In-silico clinical treatment planning 

study seems to be feasible. We believe this is a new, complementary 

way to do clinical research. The expected outcome of the study is to identify 

(sub)groups of patients who might benefit from particle therapy or any new innovative 

irradiation modality (e.g. Tomotherapy). These findings will obviously 

to be validated in prospective trials. Furthermore the reference data-set will 

also be useful in order to improve comparisons of individual future planning 

studies. 

Treatment planning and optimisation 

298 oral 

4D STEREOTACTIC LUNG IMRT PLANNING USING MONTE-CARLO 

DOSE CALCULATIONS ON MULTIPLE RCCT-BASED DEFORMABLE 

GEOMETRIES 

M. Söhn 1 , D. Yan 2 , M. Alber 1 

1 

UNIVERSITY OF TÜBINGEN, Section for Biomedical Physics, Radiooncological 

Clinic, Tübingen, Germany 

2 


Purpose: To fully address the problems of stereotactic treatment of moving 

lung lesions, the dose-to-moving-tissue instead of a static dose distribution 

should be optimized in IMRT-planning. This requires dose warping during optimization 

based on deformation fields obtained from deformable registration 

between multiple phases of a respiratory correlated CT (RCCT) dataset. Simultaneously, 

Monte Carlo (MC) dose calculation is performed in multiple geometries 

to account for varying lung tissue inhomogeneities. During delivery, 

baseline-control, i.e. image-guided setup to the daily tumor mean position, is 

important for optimal 4D-planning based motion management. 

Materials: The presented 4D planning approach uses RCCT data reconstructed 

at 8-10 breathing phases, the estimated patient’s probability density 

function (pdf) of respiratory motion, the contoured volumes of the CTV and 

OARs at a reference phase and the deformation fields between the referenceand 

all other phases as input. The algorithm was implemented into the clinical 

IMRT-planning software Hyperion, which allows EUD-based biological optimization 

based on MC-dose distributions computed with the XVMC-code. 

During IMRT optimization, the dose is simultaneously calculated in each of 

the input CTs enhanced by uncertainty in setup and warped to the reference 

geometry using the deformation fields. The different phases are weighted according 

to the pdf of respiratory motion from the RCCT data. The resulting 

’expected dose’ as warped to the reference geometry is used during IMRToptimization. 

Accumulated DVHs and EUDs of the CTV and OARs resulting 

from this ’4D-plan’ were compared to the results of margin-based gated IMRT 

treatment at exhale position. 

Results: The algorithm implements the optimal treatment for free-breathing 

irradiation with online setup to mean tumor position. It was tested on example 

patient datasets with large target excursions. Calculation times on a dualquadcore 

Xeon PC with 2.66GHz and 16GB memory were in the order of 

an hour for a fully-segmented, MC-calculated plan. Both the 4D-approach 

and gated treatment gave similar results for target coverage and OAR doses. 

For gated treatment, however, the latter depend on the margin necessary to 

account for positional uncertainties during the gating window. 

Conclusions: Provided the availability of daily image-guided setup, the presented 

4D planning approach offers an alternative to gating by providing the 

optimal dose for free-breathing stereotactic lung IMRT treatment for patients 

with regular breathing characteristics. 

299 oral 

INTRODUCING PARETO FRONT EVALUATION AS A CONCEPT FOR 

OBJECTIVE EVALUATION OF INVERSE PLANNING AND DELIVERY 

TECHNIQUES 

R. Ottosson 1 , P. Engström 2 , D. Sjöström 1 , C. Behrens 1 , A. Karlsson 1 , T. 

Knöös 2 , C. Ceberg 2 

1 

COPENHAGEN UNIVERSITY HOSPITAL, HERLEV, Department of Oncology 

(R), Herlev, Denmark 

2 

LUND UNIVERSITY HOSPITAL, Department of Radiation Physics, Lund, 

Sweden 

Purpose: Pareto optimality is a concept that has been used within economics 

for over a century. The concept has since then been adopted by 

other branches such as engineering and computer game theory. The aim of 

the Pareto optimization is to locate the mathematically most favourable tradeoff 

for a given set of mutually contradicting objectives. A solution is said to be 

Pareto optimal when it is not possible to improve one objective without deteriorating 

at least one of the other. Thus, the Pareto concept applies well to 

the inverse planning process of external radiotherapy, which involves inherently 

contradictory objectives, high and uniform target dose on one hand, and 

sparing of surrounding tissue and nearby OAR on the other. A set of Pareto 

optimal solutions constitute the Pareto front. Due to the specific characteristics 

of a TPS or delivery technique the Pareto front for a given case is likely 

to differ from one TPS or delivery technique to another. The purpose of this 

study was to design and test a method that may be used as an evaluation 

tool for TPSs and delivery techniques. The next step in inverse planning is to 

automate the optimization process and produce a large number of Pareto optimal 

plans for treatment selection. This has already been achieved by others 

for IMRT, adding various delivery modalities would improve the benefit even 

further. 

Materials: A number of plans of varying importance regarding target conformity 

and sparing of OAR were created for different TPSs and delivery 

techniques. The DVHs of each plan were evaluated with respect to target 

coverage and dose to critical OAR. Case specific Pareto fronts were created 

based on the aforementioned parameters. 

Results: Pareto fronts were successfully sampled for all cases studied. All 

produced Pareto fronts did indeed follow the definition of the Pareto concept, 

i.e. sparing of the OAR could not be improved without target coverage being 

impaired or vice versa. Furthermore, various treatment techniques resulted in 

distinguished and well separated Pareto fronts. The plan degradation, when 

proceeding from optimal to actual fluence for both dynamic and segmented 

IMRT is included as an illustrative example of Pareto fronts as an evaluative 

tool [figure 1]. The issue of designing a model for unbiased comparison of 

parameters with such large inherent discrepancies as different TPSs or delivery 

techniques proved problematic. Different TPSs, for instance, may differ in 

strictly physical parameters, such as mean dose, while biological parameters, 

such as TCP may be comparable. 

Conclusions: It is quite possible to use Pareto front evaluation as a comparative 

tool for a number of parameters in radiotherapy. Examples of such 

parameters are optimization algorithms of TPSs, the variation between accelerators 

or delivery techniques and the degradation of a plan during the 

treatment planning process, i.e. from optimal fluence to actual fluence.


300 oral 

THE BENEFIT OF BIOLOGICAL OPTIMISATION OF IMRT FOR 

NORMAL TISSUES: SEVEN YEARS OF CLINICAL EXPERIENCE. 

M. Alber 1 , G. Nguyen 2 , A. Horst 3 , B. Frey 3 , M. Söhn 1 , U. Ganswindt 2 , 

C. Belka 2 

1 

UNIVERSITY OF TÜBINGEN, Section for Biomedical Physics, Tübingen, 

Germany 

2 

UNIVERSITY OF TÜBINGEN, Clinic for Radiooncology, Tübingen, Germany 

3 

UNIVERSITY OF TÜBINGEN, Section for biomedical physics, Tübingen, 

Germany 

Purpose: The use of biological cost functions for normal tissues in IMRT 

optimization results in typical features of the dose distributions in a population 

of patients, which deviate from the past 3D conformal experience. By means 

of statistical analysis of dose distributions and follow-up data, we try to assess 

the benefit of biological optimisation for normal tissues on a data base of 

nearly one thousand treatments. 

Materials: Starting in September 2001, all IMRT treatments were optimized 

using EUD-based class solutions. Thus, the treatments were highly standardized 

with respect to normal tissue dose distributions. The normal tissue 

DVHs of various patient groups (prostate, head-and-neck) were pooled and 

subjected to a principal component analysis. Further, normal tissue response 

data was available to search for correlations of treatment-related complications 

and DVH features. 

Results: Due to the variability of patient geometry, it is inevitable that a standardized 

treatment technique induces a certain spread in dose distributions 

in a population. With biological cost functions and IMRT, this spread tends to 

be smaller, mostly because patients with a very unfavourable geometry obtain 

a treatment plan where the potential of IMRT to spare normal tissues is 

used better. By means of the PCA, it can be shown that the dominant modes 

of dose variability in a patient population are isotoxic, i.e. even if there is a 

deviation from the mean dose distribution, it is not to the detriment of the patient. 

This finding is model-independent and based on a previous outcome 

analysis for prostate patients treated with 3D CRT. No feature of the biologically 

optimized dose distributions could be identified that correlate with the 

risk of rectal bleeding. Since the overall incidence of complication was very 

low, the observed complication rate is associated with a large uncertainty. In 

contrast, it is straightforward to express the mean and variance of the delivered 

EUDs, which makes the latter a more pragmatic parameter for clinical 

class solutions. 

Conclusions: Biological optimisation for normal tissues reduces the risk of 

complications in a population mostly by keeping a tighter control on the dose 

in a situation of unfavourable patient geometry. 

301 oral 

INCORPORATING UNCERTAINTIES IN RESPIRATORY MOTION 

INTO TREATMENT PLAN OPTIMIZATION 

E. Heath 1 , J. Unkelbach 2 , U. Oelfke 1 

1 

DEUTSCHES KREBSFORSCHUNGZENTRUM, Medical Physics, Heidelberg, 

Germany 

2 



Purpose: Inverse planning methods which incorporate organ motion 1 have 

the potential to deliver a highly conformal dose to tumors which are affected 

by respiratory motion. However, these methods assume that throughout the 

S 97 

treatment process the patient breathing motion is consistent with the motion 

model derived from the 4D CT images. It is known that inter and intra-fraction 

variations in patient breathing patterns can occur 2 , in which case the dose 

distribution planned on the 4D CT motion model may not be realized. 

Materials: A probabilistic approach to inverse planning in the presence of organ 

motion was previously developed 3 . The method minimizes an objective 

function which sums the quadratic difference between the expectation and 

prescribed dose values with the variance of the dose in the target volume. We 

have extended this method to account for variations in the respiration motion 

amplitude and baseline exhale position. The variance of the dose in each 

target voxel was determined by evaluating the cumulative dose for different 

motion trajectories based on an amplitude and exhale position sampled from 

a probability distribution. Treatment plans optimized with and without variance 

minimization were evaluated for a 6-field lung patient. The peak-to-peak tumor 

motion amplitude was 2.5 cm and a normal distribution with a standard 

deviation of +/- 5 mm was used to characterize the deviations of the motion 

amplitude and exhale position from the nominal values. To visualize the dose 

uncertainty in the target volume, cumulative dose volume histograms (DVHs) 

were calculated for each sampled amplitude and exhale position. 

Results: Dose distributions and corresponding target DVHs are shown in 

Figure 1. For the case of a single fraction delivery (1b), the planned dose distribution 

for the variance minimization plan resembles a safety margin planning 

approach. For this plan, the expectation value of the target dose in 

the presence of respiratory motion trajectory variations is in close agreement 

with the cumulative target dose for the nominal trajectory (1e). If variance 

minimization is not included in the objective function, the target dose coverage 

is significantly reduced in the presence of motion variations. Inspection 

of the individual DVHs for a +/-5 mm variation in amplitude and exhale position 

demonstrate that the plan with variance minimization is less sensitive to 

changes in the motion trajectory. 

Conclusions: We have developed an inverse treatment planning method 

which incorporates information about variability in respiratory motion. The 

method allows an automated determination of treatment plans which maximize 

target dose conformality while minimizing the dosimetric impact of such 

variations and can be extended to include other uncertainties in 4D patient 

models such as image registration errors.(1) Trofimov A., Rietzel E., Lu H-M., 

Martin B., Jiang S., Chen G.T.Y. and T. Bortfeld "Temporo-spatial IMRT optimization: 

concepts, implementation and initial results" Phys. Med. Biol. 50 

2779-2798 (2005). (2) Sonke J-J., Lebesque J. and M. Van Herk "Variability 

of four-dimensional computed tomography patient models" Int. J. Radiation 

Oncology Biol. Phys. 70 590-598 (2008). (3) Unkelbach J. and U. Oelfke "Inclusion 

of organ movements in IMRT treatment planning via inverse planning 

based on probability distributions" Phys. Med. Biol. 49 4005-4029 (2004).


302 oral 

EVALUATION OF OPTIMAL MARGIN RELATED TO THE RES- 

PIRATION INDUCED INTRAFRACTIONAL TUMOUR POSITION 

UNCERTAINTY OF NON-SMALL CELL LUNG CANCER PATIENTS 

C. Brink 1 , M. Nielsen 1 , M. Baker 1 , S. Korreman 2 , O. Hansen 3 

1 

ODENSE UNIVERSITY HOSPITAL, Laboratory of Radiation Physics, Odense, 

Denmark 

2 

RIGSHOSPITALET, COPENHAGEN UNIVERSITY HOSPITAL, Department of 

Radiation Oncology 

3 

ODENSE UNIVERSITY HOSPITAL, Department of Oncology, Odense, 

Denmark 

Purpose: Radical radiation treatment of lung tumours often includes large 

radiation fields due to the risk of internal tumour movement. This leads to 

restrictions on the treatment dose in order to avoid unacceptable risks of radiation 

induced normal tissue complications (NTCP). If treatment fields are reduced 

in size, part of the tumour may be outside the treated volume for some 

fraction of the radiation time. However, the decrease in treatment field area 

allows an increase in MU per treatment for a given level of NTCP, and this 

might compensate for the partial "tumour-miss". Time resolved cone-beam 

CT becomes available in many institutions very soon and this will reduce the 

inter-fractional uncertainty. However, the respiration will still introduce intrafractional 

uncertainties. 

Materials: The patients are 4D CT scanned and the CTV is outlined in one 

of the respiration phases and automatically transferred to the other phases. 

Based on the mid-ventilation phase and a PTV created from the CTV using 

a margin recipe including the breathing uncertainty, a standard 5 field plan is 

produced (66 Gy / 33 fractions). The plan is subsequently transferred to the 

other respiration phases such that DVH’s averaged over the respiration cycle 

(dose probability histogram) for the CTV can be calculated. The reference 

frame of the study consists of the dose probability histogram of the CTV and 

lung tissue.Afterward the treatment fields are reduced in size by 2.5 and 5 

mm in all directions, and the calculations repeated. Due to the reduced size 

of the treatment field the mean lung dose (MLD) based on the dose probability 

histogram is decreased. Using MLD as a predictor of pneumonitis the dose 

per fraction is increased such that the MLD value for the new plans equals the 

reference value. Having established the same risk of pneumonitis the dose 

probability histograms for the CTV for the new plans can be compared with 

the one for the reference plan. 

Results: Currently 6 patients have been analysed in the study. Reduction 

of the margins allows a large escalation in isocenter dose (~10% and ~20% 

for 2.5 and 5 mm reduction, respectively) for fixed lung damage. Likewise 

the mean dose to the CTV increases with approximately the same values. 

More interesting, even the minimum isodose curve surrounding 99% of the 

CTV D(99), did also increase by ~9% and ~17% for 2.5 and 5 mm reduction, 

respectively (~64Gy for the standard plan, ~70 Gy for 2.5 mm and ~75 Gy for 

5 mm). 

Conclusions: A reduction in the margins from CTV to PTV will lead to a large 

reduction in treated normal lung tissue and, correspondingly, an increased 

number of MU’s can be delivered without increasing the risk of pneumonitis. 

As a result, the CTV receives a larger dose than the dose in the reference 

plan (standard margins). This is likely to increase the local control probability. 

At the conference we expect to present data for approximately 20 patients. 

303 oral 

INVERSE TREATMENT PLANNING IN 3D IMAGE GUIDED INTRA- 

CAVITARY BRACHYTHERAPY FOR CERVICAL CANCER 

K. Tanderup 1 , S. K. Nielsen 2 , J. C. Lindegaard 1 

1 

AARHUS UNIVERSITY HOSPITAL, Department of Oncology, Aarhus C, 

Denmark 

2 

AARHUS UNIVERSITY HOSPITAL, Department of Medical Physics, Aarhus 

C, Denmark 

Purpose: 3D image guided brachytherapy in cervical cancer rely on careful 

optimisation of the treatment plan. Inverse planning (IP) is a new tool for dose 

optimisation which is still relatively unexplored in this setting. The purpose 

of this study was to compare inverse and manual dose planning (MP) with 

regard to: 1) feasibility of planning procedure and 2) dose volume parameters 

in tumour and organs at risk. 

Materials: Dose plans of 10 cervical cancer patients (IB1: 2pt, IIB: 8 pt) 

with tumour diameter 85Gy; bladder: D2cc < 90 Gy; rectum and sigmoid: D2cc < 75 Gy. With 

IP the loading in the ring (and thereby the dose to the vagina) was controlled 

by using a system feature which generates a reference line around the ring to 

which a dose constraint can be applied during optimisation. Visual inspection 

of the isodose curves was performed to evaluate the difference between MP 

and IP in spatial dose distribution. 

Results: Mean tumour volume was 34±11 cc. IP was fast (< 10 min) and 

easy to use whereas the time for MP was longer and operator dependent 

(approx. 20-40 min). With IP the dose in the vaginal region could be more 

reproducibly controlled than with MP. Small manual adaptations to dwell times 

were performed after IP in 4/10 cases. All DVH constraints were respected in 

all patients for both MP and IP. With IP a modest increase was seen in D90 

from 95Gy to 97Gy. There was no significant difference between MP and IP 

regarding dose to organs at risk and regarding the size of overdose volumes 

irradiated to more than 200% of prescribed dose. The spatial distribution of 

overdose volumes was similar for IP and MP. 

Conclusions: This study shows that IP is feasible in intracavitary brachytherapy 

and results in dose plans which are comparable to or slightly better than 

obtained with MP. The great advantage of IP is speed and reproducibility. For 

larger tumours and more complex brachytherapy implants, the advantages of 

IP are currently being explored and are expected be even more pronounced. 

Treatment of cancer int the pelvic region 

304 oral 

INTERFRACTION CTV SHAPE VARIABILITY OF RECTUM CANCER 

PATIENTS. 

R. de Jong 1 , J. Nijkamp 1 , J. Duppen 1 , J. J. Sonke 1 , C. van Vliet 1 , C. 

Rasch 1 , C. Marijnen 1 

1 THE NETHERLANDS CANCER INSTITUTE-ANTONI VAN LEEUWENHOEK 


Purpose: Changes in rectum and bladder filling cause large geometrical uncertainties 

during radiotherapy of rectum cancer patients. In our department 

this leads to generous delineations (~10 mm outside mesorectal fat at the 

anterior border), combined with a 10 mm PTV margin. The actual geometrical 

uncertainties and required PTV margins however, are currently unknown. 

The purpose of this study was to quantify the CTV shape changes occurring 

during radiotherapy of rectum cancer patients treated pre-operatively with 5x5 

Gy. 

Materials: Interfraction CTV shape variability was assessed on Cone-Beam 

CT (CBCT) scans acquired just prior to irradiation for 21 patients. Bony alignment 

was performed. Since no major shape changes were expected in the 

nodal areas, only the mesorectal fat was delineated as a surrogate CTV (s- 

CTV) on the planning CT and on each CBCT scan. In addition, rectum and 

bladder were delineated. Mean and standard deviation (SD) of the difference 

between the CBCT scans and planning CT s-CTV delineations were calculated 

per patient and converted to surface maps. A surface maps is a rectangular 

representation of the recum, where the horizontal axis represents the 

2D polar coordinate (0-360 degrees) and the vertical axis the cranial-caudal 

distance to the anus, normalized to the distance between anus and the caudal 

part of the sacro-iliac joints. Group statistics were quantified by systematic 

and random errors calculated for each pixel of the surface map. 

Results: The systematic (Σ) and random (σ) errors varied substantially for 

different regions of the s-CTV. Errors, both Σ and σ, up to 8 mm were found 

on the anterior upper-middle part of the s-CTV (e.g. starting at the bottom 

end of the bladder). At the lateral and dorsal borders of the s-CTV the errors 

were relatively small except for below the os coccyx (tail bone). The large 

systematic and random errors in the upper-middle part were mainly caused 

by differences in bladder and rectum filling. Errors below the os coccyx seem 

to be caused by differences in muscle tension. 

Conclusions: Interfraction shape variability is substantial in certain parts of 

the s-CTV. The large systematic and random errors support the generous delineations 

with a 10 mm margin, however in a subset of the patients this would 

still be insufficient to cover mesorectal fat. A non-uniform margin is under investigation 

to account for the location dependency of the shape variability. 

Different drinking protocols are tested to attempt to reduce the variation in 

bladder filling. 

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SET UP ACCURACY MEASURED WITH 6 DEGREES OF FREEDOM 

(DOF) INFORMATION FOR PELVIC RADIOTHERAPY USING TO- 

MOTHERAPY ON-LINE IMAGE REGISTRATION 

D. Routsis 1 , J. Dean 1 , R. Kirby 1 , L. Adams 2 , J. Fairfoul 2 , S. Thomas 2 , 

S. Russell 1 , H. Patterson 1 , Y. Rimmer 1 , N. Burnet 3 

1 

CAMBRIDGE UNIVERSITY HOSPITALS NHS TRUST, Radiotherapy, 

Cambridge, United Kingdom 

2 

CAMBRIDGE UNIVERSITY HOSPITALS NHS TRUST, Medical Physics, 


3 

CAMBRIDGE UNIVERSITY, Department of Oncology, Cambridge, United 

Kingdom 

Purpose: There are many uncertainties in the radiotherapy process that result 

in us being unsure that the tumour location for the treatment delivery 

is the same as that planned. Strategies to combat these uncertainties have 

been defined 1,2 but their use is dependent on each radiotherapy centre being


able to quantify the magnitude of the uncertainty. One component is the accuracy 

with which the patients’ position can be reproduced. Conventional measures 

are limited by the amount of data obtainable from 2D imaging and low 

sampling methods. Volumetric imaging with Tomotherapy provides a method 

whereby the whole of the anatomical dataset for the treatment can be visualised 

on a daily basis, showing variations with 6DoF. Rotational variations 

can be measured as well as translational. This study evaluated the complete 

variation in daily setup (internal and external) for patients having prostatic 

radiotherapy. 

Materials: 10 patients were imaged daily throughout treatment using on-line 

MVCT scanning. Patients were immobilised using indexed soft knee and ankle 

devices. Images were co-registered with the planning CT dataset and 

variations measured in all planes and rotations for 6 and 4 DoF. Comparisons 

were made using the whole CT dataset. 

Results: Data were obtained from 284 treatment fractions. Mean variations 

of 6DoF vs 4DoF were 0.96mm (2.56 SD) vs 1.07 mm (2.45 SD) laterally, 

-1.82 mm (2.56 SD) vs -1.91mm (2.90 SD) longitudinally, 5.96 mm (2.58 SD) 

vs 6.45mm (4.40 SD) vertically, and -0.01 o (0.41 SD) vs -0.02 o (0.35 SD) roll. 

Pitch measured in 6DoF was -0.02 o (1.02 SD), yaw was -0.05 o (0.48 SD). 

Conclusions: A combination of daily positioning by the radiographer and the 

immobilisation used was effective at providing daily positional reproducibility, 

however, a systematic issue seems to exist within the department. Variation 

trends were seen in the vertical and longitudinal directions; couch sag is 

being investigated. Variances exist when determining setup accuracy using 

4DoF information to 6. This should be considered when comparing setup 

reproducibilities. 1 Geometric Uncertainties in Radiotherapy. The British Institute 

of Radiology 2003 2 ICRU Report 50: prescribing, recording and reporting 

photon beam therapy 1993 

306 oral 

TUMOR RESPONSE PREDICTION BY PET-CT IN RECTAL CANCER 

USING COMPUTER AIDED AUTO-DELINEATION 

J. van den Bogaard 1 , J. Buijsen 1 , H. Aerts 1 , M. Oellers 1 , R. Beets-Tan 2 , 

R. Vliegen 3 , P. Lambin 1 , B. Vanhauten 1 , T. Eiland 1 , A. van Baardwijk 1 , 

G. Lammering 1 


2 UNIVERSITY HOSPITAL MAASTRICHT, Radiology, Maastricht, Netherlands 

3 ATRIUM MEDICAL CENTER, Radiology, Heerlen, Netherlands 

Purpose: What is the potential predictive value of a pre-therapeutic and a 

post-therapeutic FDG-CT-PET simulation for histological tumor response in 

patients treated with pre-operative chemoradiotherapy using computer aided 

auto delineation of the tumor. 

Materials: A total of 20 patients with locally advanced rectal cancer were 

included. These patients were all treated with chemoradiotherapy to a total 

dose of 50.4 Gy at 1.8 Gy/fraction, concomitant with capecitabine 825 mg/m2 

BID. Surgery was performed 6-10 weeks (mean 64 days, range 45-132) after 

completion of chemoradiation. Tumours were auto-contoured using Esoft 

image processing software. Semi-quantitative analysis was done, evaluating 

SUV values on pre- and post-scans. Furthermore SUV values were plotted 

in volume histograms and areas under the curve were calculated. To 

gain insight in the clinical significance of the changes in PET findings during 

chemoradiation ROC analysis of different parameters was performed. The 

histological evaluation of the tumor response after chemoradiation on surgical 

specimens was performed according to the TRG score by Mandard. 

Results: Tumour diameters based on PET auto-contours were not different 

between responders and non-responders. The SUVmax was significantly 

lower for responders (TRG1-2) than for non-responders (TRG3-4). Furthermore, 

a significantly higher decrease of SUVmean was observed in responders 

as compared to non-responders. ROC curve analysis of the relative 

decrease in AUC showed a cut-off point of 56% for the prediction of response 

with a sensitivity of 75% and a specificity of 69%. The same analysis revealed 

a cut-off point of 55.7% for the relative decrease (response index RI) of the 

S 99 

SUVmean resulting in a sensitivity of 100% and a specificity of 62%. For the 

RI SUVmax the cut-off was 60.3% resulting in a sensitivity and specificity of 

100% and 54%. 

Conclusions: Changes in tumor metabolism on PET-scan after chemoradiation 

are useful in the evaluation of tumor response after chemoradiotherapy. 

The response index of SUV values seems to be the best discriminating 

parameter between responders and non-responders. Tumor volume after 

chemoradiation using auto-contouring does not predict for tumour response. 

307 oral 

LONG-TERM FECAL LEAKAGE AFTER RADIOTHERAPY AND 

NEED FOR TOILET ACCESS AMONG GYNECOLOGICAL CANCER 

SURVIVORS 

G. Dunberger 1 , H. Lind 1 , G. Steineck 2 , A. C. Waldenström 3 , M. Al-Abany 

1 , U. Nyberg 4 , E. Avall-Lundqvist 5 

1 



2 

KAROLINSKA INSTITUTET/SAHLGRENSKA ACADEMY, Department of 

Clinical Cancer Epidemiology, Stockholm/Gothenburg, Sweden 

3 

SAHLGRENSKA UNIVERSITY HOSPITAL, Department of Gynecological 

Oncology, Göteborg, Sweden 

4 

ST GORAN HOSPITAL, Department of Clinical Neuroscience, Section of 

Psychiatry, Stockholm, Sweden 

5 

KAROLINSKA UNIVERSITY HOSPITAL, Department of Gynecological 

Oncology, Stockholm, Sweden 

Purpose: To investigate the impact of fecal leakage on quality of life among 

long-term gynecological cancer survivors after pelvic radiotherapy. 

Materials: A population-based study of 869 women, who had been treated 

with radiotherapy for a gynecological cancer during 1991 to 2003 at two Departments 

of Gynecological Oncology in Sweden, took place in 2006. A control 

group of 480 women from the Swedish Population Registry, matched for 

age and regional residence, was also included. In preparation, we made 

in-depth interviews with 26 women with a history of gynaecological cancer. 

Based on their narratives, we constructed a questionnaire including 351 questions 

and validated it face-to-face. The women were asked about experienced 

anatomical symptoms originating from the bowels, anal sphincter, urinary and 

genital tract, the skeleton and lower abdomen and legs. When having a symptom 

questions relating to coping strategies were added. The questionnaire 

also covered questions concerning demographics, psychological and quality 

of life factors. 

Results: Six hundred and forty nine cancer survivors (79%) and 344 

(72%) control women returned the questionnaire. Mean follow-up was 7.8 

years. The cancer survivors reported seven different symptoms of fecal 

leakage. The prevalence of fecal leakage (when having the symptom "yes" 

or "no") ranged between 7-50% among cancer survivors and between 0.9- 

17% among controls. Results from logistic regression, with forward selection 

procedures, of therapy-related symptoms showed that self experience of 

smelling feces significantly lowered quality of life (OR 2.1; 95% CI 1.3-3.6). 

The need to always have immediate toilet access, in order to avoid fecal leakage 

in clothing, was reported by 37% of survivors and 6% among controls. 

Among cancer survivors 29% had located toilet accessibility prior to leaving 

home compared to 7% among controls. Twenty six percent of the cancer survivors 

and 4 % of the controls reported the feeling of being unclean and 20% 

of the survivors and 3% of controls stated that fecal leakage had changed 

them as persons. 

Conclusions: Many long term gynecological cancer survivors treated with 

pelvic irradiation report the necessity to always have immediate toilet access 

and to locate toilet accessibility prior to leaving home, in order to avoid fecal 

leakage in clothing. 

308 oral 

HOW DOES RTT’S IN NORWAY INFORM THE PATIENT UNDERGO- 

ING RADIOTHERAPY ABOUT THE CONSEQUENCES REGARDING 

COMPLICATION AFFECTING THE PATIENTS’ SEXUAL HEALTH? 

M. Poulin Hansen 1 , S. Hjertnes 1 , L. Flatin Lien 1 , V. Kristensen 1 , T. Borg 

2 , B. Bø 1 

1 OSLO UNIVERSITY COLLEGE, Faculty of Health Sciences, Oslo, Norway 

2 RIKSHOSPITALET-RADIUMHOSPITALET MEDICAL CENTER, Oslo, Norway 

Purpose: Our thought is that it is a great variation on how information is given 

to the patient about sexual health problems, regarding radiotherapy treatment 

in Norwegian radiotherapy centers. Literature on nursing shows that there are 

different reasons why nurses choose to inform or not. Are the contributing 

factors the same for RTT’s? According to Norwegian health laws, the patient 

has a right to get information about possible risks and consequences caused 

by his/hers treatment. Based on these laws, our aim is to try to create a 

consciously raising around this area of responsibility. In our study we want 

to emphasize the physical, emotional, social and psychological aspects of 

sexuality. 

Materials: Our results are based on a survey given to radiotherapists at ten


different radiotherapy-centers in Norway. The participants were randomly selected. 

The selection consisted of approximately 25 % of the total amount 

of radiotherapists in Norway. We also asked the head staff/superintendent 

at the ten different centers, if they had any written procedures concerning 

information given to patients about their sexual health. 

Results: The survey shows that only one out of ten radiotherapy centers 

in Norway, have written procedures concerning information about treatment 

consequences affecting sexual health. In the other hospitals, doctors and 

nurses have the primary information role on this subject. Results show that 

even though most radiotherapists think that the patients’ sexual health is an 

important subject, the majority do not think that it is their responsibility to inform 

the patients. However, there are a minority who do inform the patients 

about problems regarding sexual health, as they did see it as their responsibility. 

In the question of whether or not they feel competent and comfortable 

providing information on the subject, the answers varies a lot. Approximately 

50 % claim that they do not feel comfortable and competent to talk about sexuality 

as a subject. Reasons for this are because of education or rather lack 

of this, differences in experience about the subject, and the fact that it is a 

hard topic to talk about, both for the patient and the staff. 

Conclusions: One out of ten radiotherapy centres in Norway have written 

procedures that includes information about sexual health. It seems as though 

the presence of written procedures have an impact on the radiotherapists 

feeling of responsibility of providing information, concerning treatment consequences 

affecting sexual health. 

Clinical Validation of Imaging 

309 oral 

BIOLOGICAL IMAGE-GUIDED RADIOTHERAPY WITH REPEATED 

FDG-PET, FMISO-PET, DCE-MRI AND DW-MRI IN HEAD AND NECK 

CANCER. 

P. Dirix 1 , V. Vandecaveye 2 , P. Slagmolen 1 , F. De Keyzer 2 , S. Stroobants 

3 , R. Hermans 2 , S. Nuyts 1 

1 

UNIVERSITY HOSPITALS GASTHUISBERG, Radiation Oncology, Leuven, 

Belgium 

2 

UNIVERSITY HOSPITALS GASTHUISBERG, Radiology, Leuven, Belgium 

3 

UNIVERSITY HOSPITALS GASTHUISBERG, Nuclear Medicine, Leuven, 

Belgium 

Purpose: To evaluate the potential of repeated FDG-PET, FMISO-PET, perfusion 

(DCE) MRI, and diffusion-weighted (DW) MRI imaging to provide an 

appropriate and reliable biological target for dose-painting. 

Materials: Twenty patients with stage III or IV head and neck cancer, treated 

with hyperfractionated RT and concomitant CT, were prospectively enrolled 

in a bio-imaging protocol. Sequential PET/CT (FDG and FMISO) and MRI 

(T1-, T2-, DCE- and DW-sequences) scans were performed before, during 

(week 2 and 4) and after RT. All images were acquired while the patient was 

immobilized in the treatment position. Non-rigid registration techniques were 

developed to register images obtained at different time points, with different 

modalities. A signal-to-background algorithm was used to delineate the GTV 

on FDG-PET/CT. The hypoxic volume (HV) was defined as the pixels with a 

tissue to blood (T/B) FMISO ratio of ≥ 1.2. DW images with a large range of 

b-values (between 0 1000 sec/mm 2 ) were obtained on a 1.5T MRI. The apparent 

diffusion coefficient (ADC) was calculated for the entire b-value range. 

Results: Median follow-up was 23 months (range: 6 52 months); actuarial 

2-year disease-free survival (DFS) was 55%. Before RT, the mean GTV was 

38.9 cc on CT, 40.1 cc on T1-MRI, 34.4 cc on T2-MRI, 24.1 cc on FDG- 

PET, and 26.9 cc on DW-MRI, respectively. On FMISO-PET, the mean HV 

was 4.1 cc and mean T/Bmax was 1.45 (range: 1.13 2.09). There was 

an excellent correlation between GTV delineation based on CT and T1-MRI 

(R = 0.98), and between FDG-PET and DW-MRI volumes (R = 0.96). No 

significant correlation between increased glucose metabolism and hypoxia 

was observed. During RT, there was considerable shrinkage of the GTV on all 

anatomical imaging modalities. There was little residual hypoxia on FMISO- 

PET scans during week 4 of RT: mean HV was 0.33 cc and mean T/Bmax 

was 1.20 (range: 0.96 1.61); there was also considerable variability in spatial 

FMISO uptake between different time-points. On DW-MRI, the mean tumor 

volume was 16.7 cc during week 2 and 9.4 cc during week 4 of RT, and 1.5 cc 

at 3 weeks after RT, respectively. In statistical analysis, DFS was significantly 

correlated with SUVmax on FDG-PET before RT (p = 0.02), T/Bmax before 

RT (p = 0.04), initial HV (p = 0.04), T/Bmax during week 4 of RT (p = 0.06), 

and the presence of residual disease on DW-MRI at 3 weeks after RT (p = 

0.01). Patients who developed a disease recurrence during follow-up had 

lower ADC values on DW-MRI at week 4 during RT (0.0014 mm 2 /sec vs. 

0.0018 mm 2 /sec, p = 0.04), and at 3 weeks after RT (0.0015 mm 2 /sec vs. 

0.0018 mm 2 /sec, p = 0.05), and a higher initial slope (23.8/s vs. 14.7/s) on 

baseline DCE-MRI. 

Conclusions: These results confirm the added value of FDG-PET and 

FMISO-PET for radiotherapy treatment planning of HNC, and suggest the 

potential of DCE- and DW-MRI for dose-painting and early response assessment. 

We are currently validating these promising results with DCE- and 

DW-MRI in a much larger patient group. 

310 oral 

FLT-PET IN HUMAN HEAD AND NECK CARCINOMAS: VALIDATION 

WITH HISTOPATHOLOGY OF SURGICAL SPECIMEN 

E. Troost 1 , A. Hoffmann 1 , P. Slootweg 2 , M. Merkx 3 , J. van Dalen 4 , A. 

van der Kogel 1 , W. Oyen 4 , J. Kaanders 1 , J. Bussink 1 

1 

RADBOUD UNIVERSITY NIJMEGEN MEDICAL CENTRE, Radiation Oncology, 


2 

RADBOUD UNIVERSITY NIJMEGEN MEDICAL CENTRE, Pathology, Nijmegen, 

Netherlands 

3 

RADBOUD UNIVERSITY NIJMEGEN MEDICAL CENTRE, Department of 

Maxillofacial Surgery, Nijmegen, Netherlands 

4 

RADBOUD UNIVERSITY NIJMEGEN MEDICAL CENTRE, Nuclear Medicine, 


Purpose: Tumour cell proliferation is one of the major resistance mechanisms 

in radiation therapy. Positron emission tomography (PET) using 18 Flabeled 

thymidine (FLT) is a non-invasive imaging modality to assess proliferative 

activity. Functional information obtained by FLT-PET might be employed 

for individualized treatment planning and early response monitoring. However, 

before applying this in clinical practice, FLT-PET should be validated 

against histopathology, including established immunohistochemical staining 

methods. This was the aim of the current study. 

Materials: Twenty-two patients with stage T2T4 squamous cell carcinomas 

of the head and neck eligible for surgical tumour resection were included. 

Prior to surgery, a co-registered FLT-PET and contrast-enhanced CT scan 

were acquired. Twenty minutes before the operation, the proliferation marker 

iododeoxyuridine (IdUrd) was intravenously administered. From the fresh tumour 

resection specimen a representative sample was taken, and a 5 µm 

section was immunohistochemically stained for IdUrd. The IdUrd labelling 

index (IdUrd-LI) was calculated for the entire tumour section and also in selected 

regions of interest with highest proliferative activity. The gross tumour 

volume (GTV) was visually delineated on CT (GTVCT) and on FLT-PET applying 

two delineation protocols: static thresholding using a 50% isocontour 

of the maximum tumour signal (GTV50%) and adaptive thresholding using a 

tumour-to-background dependent threshold (GTVTBR). The mean standardised 

uptake value (SUVmean) within these PET volumes was calculated and 

correlated to IdUrd-LI. 

Results: All 22 pathologically confirmed primary tumours were visualised by 

FLT-PET compared to 17 by CT (sensitivity 100% vs. 77%). The average SU- 

Vmean was 4.3 (range: 1.513.5) for GTV50%, and 4.3 (range: 1.612.9) for 

GTVTBR. In most tumours, IdUrd staining was heterogeneously distributed 

with areas of high and low proliferation. The average IdUrd-LI for the entire 

tumour sections ranged from


Results: In figure 1 the best overlap of the suspicious regions found with 

both techniques is shown for one patient. Even the best possible overlap 

of suspicious regions is limited. Similar results are found for all patients, the 

best possible DC between suspicious regions ranged from 0-0.5 for the entire 

prostate and 0-0.6 when only the PZ was investigated. 

Conclusions: Poor overlap is found between regions with low ADC values 

and high Ktrans values. This implies that simultaneous diffusion and perfusion 

imaging provides complementary functional data, which can help to 

improve tumor delineation. As the difference in perfusion and diffusion data 

may reflect actual differences in tumor physiology, one should be careful with 

tumor delineation based on one of these functional imaging techniques only. 

312 oral 

PETCT FOR TARGET VOLUME DEFINITION AND EVOLUTION IN 

RECTAL CANCER 

S. Roels 1 , P. Slagmolen 2 , J. Nuyts 3 , S. Stroobants 3 , F. Penninckx 4 , K. 

Haustermans 1 

1 UNIVERSITY HOSPITAL LEUVEN, Radiation Oncology, Leuven, Belgium 

2 UNIVERSITY HOSPITAL LEUVEN, Medical Image Computing (ESAT/PSI), 

Faculties of Medicine and Engineering, Leuven, Belgium 

3 UNIVERSITY HOSPITAL LEUVEN, Nuclear Medicine, Leuven, Belgium 

4 UNIVERSITY HOSPITAL LEUVEN, Abdominal Surgery, Leuven, Belgium 

Purpose: The purpose of this study is to investigate the use of 

[18F]fluorodeoxyglucose (FDG), [18F]32-deoxy-32-fluorothymidine (FLT) and 

[18F]fluoromisonidazole (FMISO) PETCT for RT target definition and evolution 

in rectal cancer. 

Materials: In 15 patients, FDG PETCT was performed before and during 

preoperative radiotherapy for resectable rectal cancer. Ten patients received 

additional FMISO PETCT and 5 patients additional FLT PETCT on the same 

time points. All PET signals were automatically delineated with a gradientbased 

segmentation algorithm and non-rigid registration algorithms were applied 

to register the different images to the corresponding CT. Mismatch analyses 

were carried out to quantify the resulting overlap between FDG and 

FLT/FMISO volumes and between PET volumes over time to assess how the 

different volumes correspond after registration. The mismatch of a certain 

volume A to a certain volume B is defined as the percentage of A that does 

not belong to B. 

Results: Ninety sequential PETCT images were analyzed from 15 patients. 

The mean FDG, FLT and FMISO PET volumes showed a tendency to shrink 

during preoperative RT (Figure). On each time point, FMISO volumes were 

significantly smaller than the corresponding FDG volumes (Wilcoxon Matched 

Pairs Test). FLT PET volumes were also smaller but not significantly. The 

results of the mismatch analyses between the PET tracers showed a mean 

65% mismatch between the FMISO and FDG volumes obtained before RT 

S 101 

(range: 35%-100%). The same result was seen during RT (65% mismatch 

(38%-87%)). FLT volumes showed a better overlap with the corresponding 

FDG volumes (mean 25% (12%-41%) mismatch before RT and 51% (19%- 

78%) during RT. Registration of the PET volumes taken before and during 

RT revealed that on average 61% (0%-94%) of the FDG volume during RT 

overlapped with the baseline FDG. For FMISO, only 20% (0%-71%) of the 

volume during RT remained inside the contour of the baseline volume. For 

FLT, the corresponding volume overlap was 49% (0%-90%). 

Conclusions: FDG, FLT and FMISO PET signals reflect different functional 

characteristics that change during RT. FLT and FDG show a good spatial correspondence, 

while FMISO demonstrates more variance compared to FDG, 

most likely due to false positive physiological uptake in the bowel. Moreover, 

the signal uptake seems less stable over time compared to FDG and 

FLT. FDG and FLT PETCT imaging seem most appropriate to integrate in the 

(adaptive) preoperative RT treatment for rectal cancer.


313 oral 

EARLY PREDICTION OF RADIATION-INDUCED LUNG DAMAGE 

(RILD) USING FDG UPTAKE PATTERNS IN THE LUNG 

A. Dekker 1 , A. Houben 1 , P. Lambin 1 , D. De Ruysscher 1 

1 DEPARTMENT OF RADIATION ONCOLOGY (MAASTRO), GROW - SCHOOL 

FOR ONCOLOGY AND DEVEL, Radiation Oncology, Maastricht, Netherlands 

Purpose: Radiation therapy is frequently used to treat tumors in and around 

the thoracic region, such as lung and breast cancer. A commonly found complication 

is radiation-induced lung damage (RILD), which can result in significant 

morbidity. An accurate prediction of the risk at RILD is therefore of great 

clinical importance. At present, dosimetric parameters such as the MLD are 

used to predict RILD in NSCLC patients, but they have a low accuracy with 

typically AUC’s of 0.60. It is already suggested in literature that the SUV uptake 

is measure of inflammation of the lung tissue. We hypothesized that the 

FDG uptake in the lung as well as the concentration of IL-6 in the blood, early 

during radiotherapy, would reflect subclinical RILD and hence be predictive 

for later development of RILD. 

Materials: An FDG-PET-CT scan was made on day 0, day 7 and day 14 after 

initiation of radical radiotherapy in 18 patients. The SUV uptake pattern 

of the lung tissue minus the gross tumor volume was determined. The highuptake 

regions were defined as the regions of the lung with a SUV > x, with x 

ranging from 1 to 2,5. The volumes of high uptake regions were normalized 

for the total lung volume of that day, to exclude volume influences. Performance 

of the model was expressed as the area under the curve (AUC) of 

the receiver operating characteristic (ROC) and assessed using leave-oneout 

(LOO) cross-validation. The maximum value of the AUC is 1.0; indicating 

a perfect prediction model. A value of 0.5 indicates that patients are correctly 

classified in 50% of the cases, e.g. as good as chance. 

Results: 18 Patients are included in this study from which 6 develop RILD ≥ 

grade 2, CTCAE v3.0. The delta SUV (>1,5) between day 14 and day 0 was 

highly predictive for the risk at RILD (AUC = 0,83), using an LOO algorithm. 

The IL-6 concentration does not correlate with the incidence of RILD. 

Conclusions: The increase of FDG uptake in the high-uptake (SUV>1,5) regions 

of the normal lung during radiotherapy within the first two weeks, was 

highly predictive (AUC = 0,83) for subsequent clinical RILD. Larger cohort 

of patients, prospective coinformation and external validation are needed. 

These high risk patients may benefit from trials to prevent RILD. 

314 oral 

PRE-TREATMENT FMISO HYPOXIC VOLUME IS A SIGNIFICANT 

PROGNOSTIC FACTOR FOR LOCAL CONTROL AFTER IRRADIA- 

TION OF FADU HNSCC XENOGRAFTS 

C. Schütze 1 , R. Bergmann 2 , B. Mosch 3 , A. Yaromina 1 , F. Hessel 1 , 

M. Krause 1 , H. Thames 4 , D. Zips 1 , P. Mäding 5 , M. Baumann 6 , B. 

Beuthien-Baumann 7 

1 

MEDICAL FACULTY CARL GUSTAV CARUS, UNIVERSITY OF TECHNOLOGY, 

Department of Radiation Oncology, OncoRay Center for Radiation Research 

in Oncol, Dresden, Germany 

2 

PET-ZENTRUM FORSCHUNGSZENTRUM DRESDEN ROSSENDORF, Division 

of Radiopharmaceutical Biology, OncoRay Center for Radiation Research in 

O, Dresden, Germany 

3 

PET-ZENTRUM FORSCHUNGSZENTRUM DRESDEN ROSSENDORF, Radiopharmaceutical 

Biology Division , Dresden, Germany 

4 

UNIVERSITY OF TEXAS M.D. ANDERSON CANCER CENTRE, Department 

of Biostatistics and Applied Mathematics, Houston, USA 

5 

PET-ZENTRUM FORSCHUNGSZENTRUM DRESDEN ROSSENDORF, Radiopharmaceutical 

Production Group , Dresden, Germany 

6 

MEDICAL FACULTY CARL GUSTAV CARUS, UNIVERSITY OF TECHNOLOGY, 


7 

UNIVERSITÄTSKLINIKUM CARL GUSTAV CARUS, Department of Nuclear 

Medicine, OncoRay Center for Radiation Research in Oncolog, Dresden, 

Germany 

Purpose: To investigate whether pre-treatment FMISO hypoxic tumour volume 

(HV) adds significant information about radiotherapy outcome in FaDu 

human squamous cell carcinoma (hSCC) in nude mice. 

Materials: The hSCC cell line FaDu was transplanted subcutaneously into 

the hind leg of NMRI nude mice. Seventy animals entered the study at tumour 

volumes ranging from 165-343 mm. [ 18 F]fluoromisonidazole ([ 18 F]FMISO)- 

PET scanning was performed under anesthesia on a dedicated animal PET 

scanner (MicroPET R○ P4, CTI Molecular Imaging Inc, measured attenuation 

correction, 11 MBq 18 FMISO i.v., list mode acquisition for 30 min after 210 

min p.i). The regions of interest (ROI) include the FMISO positive hypoxic volume, 

the mean, the maximum concentration (ROVER software, ABX GmbH, 

Radeberg, Germany). After an initial FMISO-PET (day 0) the tumours were 

stratified according to the median hypoxic volume (HV) for single dose irradiation 

with either 25 Gy or 35 Gy under normal blood flow conditions using 

200 kV X-rays (0.5 mm Cu, ~1.2 Gy min -1 ). The endpoints were local tumour 

control and time to local failure. Five animals are currently still in follow up. 

Results: Tumour local control rate after irradiation with 25 Gy was lower than 

after irradiation with 35 Gy (22% vs. 69%, log rank p


Conclusions: The evaluation at 10 years of follow-up confirms the 5-year 

results showing similarity of the outcome with the external electron, external 

photon or brachytherapy techniques for delivering a boost dose to the primary 

tumour bed in the framework of breast conserving therapy. 

316 oral 

PERSISTING RISKS IN PRE-MENOPAUSAL BREAST CANCER 

PATIENTS AFTER STANDARD THERAPY (BCS, RT, +/- SYSTEMIC 

THERAPIES) 

J. Hammer 1 , C. Track 1 , D. H. Seewald 1 , J. Feichtinger 1 , H. Thames 2 , A. 

L. Petzer 3 , W. Langsteger 4 , K. J. Spiegl 1 , S. Pöstlberger 5 , E. Bräutigam 1 

1 

BARMHERZIGE SCHWESTERN HOSPITAL, Radiation Oncology, Linz, Austria 

2 

M.D.ANDERSON CANCER CENTER, Biostatistics and Applied Mathematics, 

Houston, USA 

3 

BARMHERZIGE SCHWESTERN HOSPITAL, Department of Internal Medicine 

/ Hematology and Oncology, Linz, Austria 

4 

BARMHERZIGE SCHWESTERN HOSPITAL, Nuclear Medicine, Linz, Austria 

5 

BARMHERZIGE SCHWESTERN HOSPITAL, Surgery and Breast Health 

Center, Linz, Austria 

Purpose: To evaluate which risk parameters gain in importance after breast 

conserving surgery (BCS), systemic therapy (ST) and radiation therapy (RT) 

in pre-menopausal women. 

Materials: From 1984 to 1999, 2208 patients with T1-2 N0-1 breast cancer, 

who underwent BCS ± ST, were referred to radiotherapy. In 1696 of them all 

variables used in this analysis were available. 575 out of this subgroup were 

pre-menopausal. Margin status was tumour-free in 564 patients (98.1%). R1 

resection in 7 patients and 4 with unknown margins: 4 of them presented 

with recurrent disease during follow up. Recursive partitioning analysis was 

carried out for the endpoints local recurrence (LR), disease free survival rate 

(DFR) and disease specific survival (DSS). Co-variates included were age, 

T-stage, T-size (mm), N-stage, ratio of involved lymph nodes and excised 

nodes (n-ratio, NR), location of the index tumor (loc), ER and PR status, and 

menopausal status. The number of positive axillary nodes did not become 

significant whenever NR was included in the statistical fit. The relative hazard 

ratio (RHR, HR relative to the median patient) was estimated in sub-groups 

of at least 25 patients. Constraint: p ≤ 0.05. 

Results: After a mean f/u of 122 months the rate of LR at 10 years was 8.9% 

(all patients 5.8%, post-menopausal 4.1%), the DFR was 76.0% (all 80.3%, 

post-meno 83.0%), and DSS was 87.0% (all 88.5%, post-meno 89.3%) in 

this young patient set. For LR the most relevant parameter is T-size with a cut 

point at 25.5 mm (10-yr LR rate 7.6% vs. 20.6%), followed by age and tumour 

location. For DFR there is a low cut point in NR of 16% (10-yr: 16%: 45.5%), followed by T-size and PR, and age in the third level. The 

worst 10-yr DFS rate is given in patients with NR >16% and PR neg: 26.7%! 

For DSS the NR again is the most significant prognostic factor with a cut 

point at 16% (10-yr rate 90.2% vs. 65.0%), followed by T-size and grading. 

The number of positive axillary nodes was insignificant whenever the node 

ratio was included in the statistical analysis. 

Conclusions: We hypothesize that after BCS, ±ST, and RT, subgroups of 

young patients are at higher risk; in LR determined by T-size and age. Higher 

risk is also indicated for medially and centrally located tumours. High risk in 

the survival parameters is determined mostly by NR, PR negativity, T-size, 

age and grading. The 10-year rates of these subgroups indicate that these 

patients may need a more aggressive therapy. A dramatically low survival rate 

is given in patients presenting with NR >16% and negative PR. The present 

results differ from most published reports, where tumour location is not found 

critical to the likelihood of local recurrence. 

317 oral 

EVALUATION OF TUMOUR BED LOCALISATION AND IMAGE- 

GUIDED RADIOTHERAPY FOR BREAST CANCER: THE IMPORT 

GOLD SEED STUDY 

C. Coles 1 , G. Wishart 2 , J. Wilkinson 1 , S. Vowler 3 , J. Vasconcelos 3 , 

E. Donovan 4 , J. Fairfoul 1 , E. Harris 4 , C. Mackenzie 5 , D. Routsis 1 , A. 

Poynter 5 , C. Rawlings 6 , N. Twyman 1 , R. Wilks 6 , J. R. Yarnold 4 

1 

CAMBRIDGE UNIVERSITY HOSPITALS NHS FOUNDATION TRUST, Oncology 

Centre, Cambridge, United Kingdom 

2 

CAMBRIDGE UNIVERSITY HOSPITALS NHS FOUNDATION TRUST, Cambridge 

breast Unit, Cambridge, United Kingdom 

3 

CENTRE FOR APPLIED MEDICAL STATISTICS, Cambridge, United Kingdom 

4 

ROYAL MARSDEN HOSPITAL NHS TRUST, Institute of Cancer Research, 

London, United Kingdom 

5 

IPSWICH HOSPITAL NHS TRUST, Oncology Department, Ipswich, United 

Kingdom 

6 

TORBAY HOSPITAL, Oncology Department, Torquay, United Kingdom 

Purpose: The UK IMPORT (Intensity Modulated Partial Organ Radiotherapy) 

trials hypothesise that breast irradiation can be tailored according to a 

woman’s risk of local recurrence. Accurate tumour bed (TB) localisation is 

essential for both planning and delivery of more complex risk-adapted radio- 

S 103 

therapy (RT). The aim of this multicentre study is to investigate the feasibility 

of implanted gold seeds for TB localisation and image-guided radiotherapy 

(IGRT) and inform protocol development for the IMPORT HIGH trial. 

Materials: For each patient, 6 gold seeds were implanted around the TB. 

Successful seed insertion was defined as 6 seeds correctly positioned. TB 

localisation was carried out following the CT planning scan by outlining the 

gold seeds and associated seroma/architectural distortion. Successful use 

of seeds for CT planning was defined as unique identification of all 6 seeds. 

An additional study CT scan was carried out in the last week of RT to give 

the change in TB volume. Inter and intra-observer variability in TB outlining 

was also investigated with 5 clinicians outlining 5 CT datasets on 2 separate 

occasions. The patients were treated with standard whole breast RT. Portal 

imaging (PI) was carried out for a maximum of 15 fractions. Successful use 

of seeds for portal imaging was defined as at least 3 seeds uniquely identified 

to give daily couch displacement co-ordinates in a minimum of 10 out of the 

15 fractions. 

Results: 51 patients were recruited from 4 UK oncology centres, and the 

success rates for insertion, CT localisation and PI assessment were 88%, 

95% and 100% respectively. The median times for surgical insertion, CT 

localisation and PI assessment were 9, 10 and 8 minutes respectively. Median 

change in TB volume between CTs was -9.33 cm3 (95% CI: -15.54 to 

-3.17, p 20 Gy. In this patients 

the mean movement of the diaphragm was 26 mm against 16 mm for patients 

with dose reduction 20 Gy) and 5.2 mm (> 20Gy) (p=0.05). 

Conclusions: Irradiation only in the inspiration phase significantly reduce 

radiation dose to the heart and especially to the anterior wall of the heart. 

Patients with maximal use of the diaphragm (abdominal breathing) seem to 

profit more from treating only in inspiration. 

319 oral 

DEATH OF ISCHEMIC HEART DISEASE 10-19 YEARS AFTER 

TREATMENT FOR EARLY BREAST CANCER: A POPULATION- 

BASED NESTED CASE-CONTROL STUDY REGARDING ABSORBED 

DOSE TO THE HEART AND 11 ANATOMICAL SUBSTRUCTURES OF


THE HEART 

M. Perman 1 , I. Johanson 2 , B. Ohlson 3 , K. A. Johansson 3 , P. Karlsson 1 

1 


2 

SAHLGRENSKA UNIVERSITY HOSPITAL, Oncological Center, Göteborg, 

Sweden 

3 

SAHLGRENSKA UNIVERSITY HOSPITAL, Radiation Physics, Göteborg, 

Sweden 

Purpose: It is well established that absorbed dose to the heart is associated 

with increased late cardiovascular mortality for breast cancer patients. The 

dose-volume-effect relationships for different substructures of the heart, including 

the left descending coronary artery (LAD) is unclear. The purpose 

of this study was to investigate dose-volume effect relationships for the different 

substructures of the heart for patients with late cardiac mortality after 

treatment for early breast cancer (EBC). 

Materials: Case subjects were defined as breast cancer patients, living in 

Gothenburg and diagnosed with EBC before 71 years of age between 1958 

and 1992, who subsequently had died from ischemic heart disease (IHD) 

10-19 years after diagnosis. 134 case subjects were identified among a population 

of 2813 patients diagnosed with EBC during this period. For each 

case subject one matched control subject was randomly selected from this 

population. Control subjects had lived as least as long after diagnosis of EBC 

as their case subjects. Radiation treatment data was collected from each individual 

patient record. The arrangements of the fields for each patient was 

reconstructed on three different CT-scans with medium-, small- and largesized 

hearts. 11 substructures and heart were delineated on the three scans 

and dose to the volumes of interest was calculated. The odds ratios (OR) for 

ischemic heart death by RT exposure or not, left-sided RT or not, right-sided 

RT or not, different intervals of dose to LAD and other substructures of the 

heart were calculated using conditional logistic regression. 

Results: Preliminary results indicate that OR for ischemic heart death by RT 

exposure or not was 10,4 (CI 4,7 - 25,0), left-sided RT or not 4,5 (CI 2,4 - 8,3), 

right-sided RT or not 1,6 (CI 0,94 - 2,8). Dose-volume data for all 12 volumes 

was evaluated for all 157 patients (108 cases and 49 controls) treated with 

radiotherapy. A significant variation of mean and maximum doses was found 

for most of the structures. Dose-volume effect relationships for heart and 

substructures will be presented at the meeting. 

Conclusions: In our population dose delivered to the heart is associated 

with increased risk of death of IHD 10-19 years after radiotherapy. For future 

developments in radiotherapy for EBC it is vital to identify which substructures 

that comprise the organ(s) at risk for late cardiac mortality. The complete 

results including ORs for dose intervals to different anatomical substructures 

of the heart will be further explored and presented at the ESTRO meeting. 

320 oral 

FOUR-YEAR TREATMENT EFFICACY BY THE AMERICAN SOCI- 

ETY OF BREAST SURGEONS (ASBS) MAMMOSITE R○ BREAST 

BRACHYTHERAPY REGISTRY TRIAL IN PATIENTS TREATED WITH 

ACCELERATED PARTIAL BREAST IRRADIATION (APBI) 

F. Vicini 1 , P. Beitsch 2 , C. Quiet 3 , A. Keleher 4 , D. Garcia 5 , H. Snider 6 , 

M. Gittleman 7 , V. Zannis 8 , H. Kuerer 9 , E. Whitacre 10 , P. Whitworth 11 , R. 

Fine 12 , B. Haffty 13 , M. Keisch 14 

1 


2 

DALLAS BREAST CENTER, Surgery, Dallas, Texas, USA 

3 

FOUNDATION FOR CANCER RESEARCH AND EDUCATION, Arizona Oncology 

Services, Scottsdale, Arizona, USA 

4 

WESTERN PENNSYLVANIA HOSPITAL, Surgery, Pittsburgh, Pennsylvania, 

USA 

5 

ST. LOUIS CANCER & BREAST CENTER, Radiation Oncology, St. Louis, 

Missouri, USA 

6 

ALABAMA BREAST CENTER, Surgery, Montgomery, Alabama, USA 

7 

SACRED HEART HOSPITAL, Surgery, Allentown, Pennsylvania, USA 

8 

BREAST CARE CENTER OF THE SOUTHWEST, Surgery, Phoenix, Arizona, 

USA 

9 

MD ANDERSON CANCER CENTER, Surgery, Houston, Texas, USA 

10 

THE BREAST CENTER OF SOUTHERN ARIZONA, Surgery, Tucson, 

Arizona, USA 

11 

NASHVILLE BREAST CARE CENTER, Surgery, Nashville, Tennessee, USA 

12 

ADVANCED BREAST CARE, Surgery, Marietta, Georgia, USA 

13 

UMDNJ-ROBERT WOOD JOHNSON MEDICAL SCHOOL, Radiation 

Oncology, New Brunswick, New Jersey, USA 

14 

CEDARS MEDICAL CENTER, Radiation Oncology, Miami FL, USA 

Purpose: Four-year data on treatment efficacy, cosmetic results and toxicities 

for patients enrolled on the American Society of Breast Surgeons (ASBS) 

sponsored MammoSite breast brachytherapy registry trial are presented. 

Materials: 1440 patients (1449 cases) with early stage breast cancer undergoing 

breast conserving therapy were treated with the MammoSite device to 

deliver adjuvant, accelerated partial breast irradiation (APBI) (34 Gy in 3.4 Gy 

fractions). 1255 patients (87%) had invasive breast cancer (IBC) (93% T1, 3% 

N1, median size = 10 mm) and 13% (n=194) had DCIS (median size 8 mm). 

Median follow-up for surviving patients was 36.6 months (range, 0-66.3). 

Results: 28 patients (1.9%) developed an ipsilateral breast tumor recurrence 

(IBTR) for a 3-yr actuarial rate of 2.15% (2.12% for IBC and 2.41% for DCIS). 

No clinical, pathologic or treatment related variables were associated with 

isolated IBTR. 4 patients (0.3%) developed an axillary failure (AF) (3-yr actuarial 

rate 0.36%). The percentage of patients with good/excellent cosmetic 

results at 12 (n=998), 24 (n=803), 36 (n=627), and 48 months (n=232 cases) 

was: 94.6%, 93.9%, 93.6%, and 91.4%, respectively. Breast seromas were 

reported in 26.8% (n=388) of cases overall (33.8% in open cavity and 21.0% 

in closed cavity implants). 12.7% of seromas were symptomatic (17.5% in 

open cavity and 8.8% in closed cavity implants). Fat necrosis was observed 

in 2.0% of all cases. A subset analysis of the first 400 consecutive cases 

enrolled was performed (352 IBC [median tumor size=10 mm], 48 DCIS [median 

size= 9 mm]). With a median follow-up of 45.9 months, the 4-yr actuarial 

rate of IBTR was 2.65% (3.00% for IBC, 0.0% for DCIS). The percentage of 

patients with good/excellent cosmetic results at 24 (n=222), 36 (n=194), and 

48 months (n=135 cases) was: 92.8%, 90.2%, and 89.6%, respectively. 

Conclusions: Treatment efficacy, cosmesis and toxicity 4 years after treatment 

with APBI using the MammoSite device are good and similar to those 

reported with other forms of APBI with similar follow-up.

TUESDAY, SEPTEMBER 16, 2008 DEBATE 

Debate 

This house believes that the treatment of choice 

for loco-regional recurrence after concomitant 

chemo-radiotherapy in HNSCC is salvage surgery 

and post-operative re-irradiation 

321 speaker 

WHICH PATIENTS ARE SUITABLE FOR SALVAGE SURGERY FOR 

LOCO-REGIONAL RECURRENCE AFTER RT 

P. Bradley 1 

1 NOTTINGHAM UNIVERSITY HOSPITALS, Nottingham, United Kingdom 

The current indication for CRT (Chemoradiotherapy) for HNSCC (Head and 

Neck Squamous Cell Carcinoma) has become blurred in clinical practice 

since it was first advocated in the VA Study 1991, which investigated operable 

advanced laryngeal cancer (Stage III/IV). Presently patients who are 

deemed "fit-enough", be they operable or inoperable (Departmental Policy!) 

are all recommended for non-surgical treatment, with the concept of ossible 

surgical salvage for persistent or recurrent disease. The sites most involved 

in such treatment policy includes larynx, oro- and hypo-pharynx and 

the neck.Persistent or recurrence of HNSCC after CRT may present locally, 

regionally or distally, or a combination of all three anatomical areas and thus 

need to be evaluated prior to any decision is made. The decision to offer salvage 

surgical treatment should be considered individually on each patient and 

should seperate the primary and regional sites, and then combine to evaluate 

the appropriate decision. Patient evaluation – the primary site after CRT is 

best performed sometime between 4 - 8 weeks, and should include CT/MRI 

and biopsy in previously operable patients only. Evaluatin of the neck is best 

performed some time between 8 - 12 weeks employing PET/CT.Factors which 

are associated wth a poor response and hence unlikely to be cured by CRT 

includes large volume disease either primary, nodal disease or when combined. 

A review of advanced laryngeal cancers showed a concentric tumour 

growth pattern was found in 77% of primary disease, while only 19% of recurrent 

tumours (CRT) had a concentric growth pattern, and were also associated 

with contralateral and dissasociate tumour cells and high evidence of 

perineural spread.Thus paients suitable for salvage surgery after CRT, must 

have been surgically curable to start with, generally have had small vlume 

disease treated with minimal bone/cartialge involvement, and physiologically 

/ psychologically able to withstand high risk complicated surgery, with its associated 

significant risks of functional morbidity and mortality. There is no 

evidence that current CRT "downsizes" tumours making inoperable tumours 

operable! Whether adding in second post-operative re-irradiation will increase 

the likely locoregional disease control with anticipated prolongation of tumour 

free survival requires testing! 

322 speaker 

POSTOPERATIVE RE-IRRADIATION AFTER SALVAGE SURGERY: 

FOR WHOM AND AT WHICH PRICE 

H. Langendijk 1 

1 UNIVERSITY MEDICAL CENTER GRONINGEN, Radiation Oncology, 


The purpose of this review is to highlight the most important developments in 

the management of recurrent or second primary head and neck carcinoma in 

previously irradiated areas by surgery and postoperative re-irradiation (RE- 

PORT) that have been published in the medical literature in the past years. 

Whenever possible, salvage surgery is considered the treatment of choice for 

recurrent and second primary HNSCC in previously irradiated areas. Patients 

eligible for surgery should have non-metastastic disease, with limited tumours 

that can be surgically resected without unacceptable morbidity and be considered 

medically fit to undergo surgery. Although salvage surgery alone can 

be relatively successful in a well-selected subset of patients, results become 

worse in more advanced recurrent stages. Especially in case of risk factors 

for locoregional recurrence, such as positive surgical margins and lymph node 

metastases with extranodal spread, the postoperative (chemo-)re-irradiation 

should be considered. Our own prospective study on REPORT showed a 3years 

locoregional control rate (LRC) and overall survival rate (OS) of 74% 

and 44%, respectively. These results did not significantly differ from the results 

obtained among patients that underwent surgery and postoperative radiotherapy 

for the first time RE-PORT patients experienced significantly more 

grade 3 and 4 neck fibrosis and laryngeal complications as compared to the 

PRI-PORT patients but no differences were observed with regard to the more 

general dimensions of quality of life. Recently, the GORTEC/GETTEC reported 

on a prospective study in which 130 patients that underwent salvage 

surgery were randomly assigned to receive full dose re-irradiation combined 

with concomitant chemotherapy (5-FU and Hydroxyurea) versus no adjuvant 

treatment. A significant improvement with regard to progression free survival 

was observed in those patients that were assigned to receive postoperative 

chemo-re-irradiation compared to those that underwent surgery alone, which 

S 105 

increased from 18% to 37% after 2 years (p=0.008). However, this benefit 

in progression free survival was not translated into a significant improvement 

of the OS. In this study, an increase was noted in grade 3 or more RTOG 

late radiation-induced morbidity. In summary it can be concluded that highdose 

postoperative (chemo)-re-irradiation can be administered safely with a 

moderate but acceptable increase in late radiation-induced toxicity. More importantly, 

the results indicate that postoperative (chemo-)re-irradiation significantly 

improves LRC among patients at risk for a second failure. Therefore, 

postoperative (chemo-)re-irradiation should be considered in these cases. On 

the other hand, as an increasing number of patients currently receive more 

effective initial treatment regimens, recurrent and second primary tumours in 

previously irradiated areas nowadays may represent a more radio-resistant 

population than reported in previous studies. Therefore, full-dose chemore-irradiation 

should only be applied in well selected cases. More attention 

should be paid to the use of advanced and emerging radiation delivery techniques, 

optimisation of fractionation and the addition of biological modifiers. 

323 speaker 

IS THERE ANY ROLE FOR BRACHYTHERAPY IN THIS CLINICAL 

SETTING 

D. Peiffert 1 

1 CRAN - CENTRE A. VAUTRIN, Department of Radiation Oncology, 

Vandoeuvre-Les Nancy, France 

Salvage brachytherapy (BT) in irradiated area is an option of treatment that 

was used for early locoregional recurrences or second primaries. Several retrospective 

series confirmed that it was possible to obtain a high rate of local 

control for lesion smaller than 2 cm, close to the rate obtained for first primaries, 

if a dose of 60 Gy or higher was delivered. The tolerance is worse with 

a risk of grade III late complications (soft tissues of bone necrosis) two times 

higher. These results open a door for combined salvage BT and surgery now 

using new tools including 3D imaging and prescription of the optimal dose 

rate. Three D dosimetry is becoming a standard for interstitial brachytherapy. 

This gives the possibility to determine the normal tissues DVH’S and target 

DVH’S. The new stepping sources afterloaders offer the possibility to optimize 

the index of conformity and COIN index. The knowledge of biological 

prognostic factors for local control and late complications after treatment of a 

first primary can then be used to improve the results for salvage treatment. 

As brachytherapy has the advantage to reduce the PTV to the volume of the 

CTV, it also gives the possibility to directly implant the sources into the target, 

with a deep fall-off of the peripheral isodoses, which gives the possibility to reduce 

the dose delivered to the adjacent organs. This was well demonstrated 

for oropharyngeal tumors, with advantages in favor of BT compared to CRT 

and IMRT. The use of a per-operative implant of the target that gives the insurance 

to be really closed to the target, improves the CTV delineation. Later 

on, it is possible to use stepping sources or even seeds, with the possibility to 

prescribe the optimal low dose rate for stepping sources, and potentially the 

very low dose rate for seeds. These arguments really comfort the possibility 

to use brachytherapy in combination with salvage surgery for treatment of locoregional 

recurrences after concomitant chemo-radiation, and open a new 

paradigm.



Brachytherapy 

324 oral 

LONG-TERM CHRONIC TOXICITY OF A DOSE ESCALATING HIGH 

DOSE RATE BRACHYTHERAPY (HDR-BT) BOOST COMBINED 

M. Ghilezan 1 , K. Marvin 1 , M. Wallace 1 , G. Gustafson 1 , L. Kestin 1 , E. 

Sebastian 1 , A. Martinez 1 

1 WILLIAM BEAUMONT HOSPITAL, Department of Radiation Oncology, Royal 

Oak MI, USA 

Purpose: To assess and compare the long-term chronic toxicity of patients 

with intermediate/high risk prostate cancer treated with a dose escalating 

HDR prostate brachytherapy boost combined with 46Gy EBRT to the pelvis, 

with a biological equivalent dose (BED) ranging from 180Gy to 306Gy. 

Materials: From December 1991 to December 2005, 439 prostate cancer 

patients with at least one intermediate/high risk factor, defined by the National 

Comprehensive Cancer Network (NCCN), were treated with a combination 

of 4-field pelvic EBRT and HDR-BT prostate boost delivered during 

the EBRT course. An escalating dose regimen was used for the HDR boost 

component of the treatment. The escalating dose level groups were: Group 

A (5.5Gyx3, 6Gyx3, 6.5Gyx3, 8.25Gy x 2), Group B (8.75Gyx2, 9.5x2) and 

Group C (10.5Gy x 2 and 11.5Gy x 2). The BED’s calculated with an alpha/beta=1.5 

were


327 oral 

INTERSTITIAL HIGH DOSE RATE (HDR) BRACHYTHERAPY + 

INTENSITY MODULATED RADIATION THERAPY (IMRT) VS. HDR 

MONOTHERAPY FOR EARLY STAGE PROSTATE CANCER : A 

REPORT OF 357 CASES 

G. Steven 1 , R. Mark 1 , P. Anderson 1 , T. Neumann 1 , M. Nair 1 , D. White 1 , 

R. Akins 2 

1 

JOE ARRINGTON CANCER CENTER, Department of Radiation Oncology, 

Lubbock, USA 

2 

UNIVERSITY OF MIAMI, Department of Radiation Oncology, Miami, USA 

Purpose: Transrectal Ultrasound (TRUS) guided interstitial implant for 

prostate cancer using High Dose Rate (HDR) + External Beam Radiation 

Therapy (EBRT) technique has been reported with results comparing favorably 

to surgery, Low Dose Rate (LDR) brachytherapy +/- EBRT, EBRT, and Intensity 

Modulated Radiation Therapy (IMRT). The role of supplemental EBRT 

in brachytherapy is controversial. We compare our results of HDR + IMRT vs. 

HDR monotherapy. 

Materials: Between 1997 and 2008, 357 patients with T1 and T2 localized 

prostate underwent TRUS guided interstitial implant. There were no Gleason 

Score or PSA exclusions. After discussion of treatment options, 109 patients 

elected HDR Implant + IMRT and 248 patients underwent HDR monotherapy. 

No patient received Hormonal Blockade. Median Gleason Score was 7 (range 

: 4 to 10). Median PSA was 9.8 (0.60 to 39.8). IMRT treatment volume 

included the prostate + seminal vesicles + 2 cm margin. Implant treatment 

volumes ranged from 42 cm3 to 196 cm3. In patients who received IMRT + 

HDR, 4500 cGy in 25 fractions was given via IMRT and 1650 cGy to 2000 cGy 

in 3 fractions via HDR. Our protocol for HDR alone, has called for two HDR 

Implants. The treatment volume received 2,250 cGy in 3 fractions prescribed 

to the 100% Isodose line, given over 24 hours. A 2nd implant was performed 

4 weeks later, delivering a further 2,250 cGy in 3 fractions, bringing the final 

dose to the prostate to 4,500 cGy in 6 fractions. Urethral dose points (12-16) 

were followed, and limited to < 105% of the prescription dose. 

Results: There was no significant difference between the treatment groups 

with respect to T- Stage, Gleason Score, and PSA. With a median follow-up 

of 88 months (range : 6 months to 144 months), the overall PSA disease 

free survival was 89.0% (318/357). In patients undergoing IMRT + HDR Implant, 

PSA disease free survival was 87.2% (95/109) vs. 89.9% (223/248) 

for patients undergoing HDR alone (p=0.46). The 5 year actuarial survival 

was 86% for the group receiving IMRT + HDR vs. 89% with HDR monotherapy 

(log rank = 0.5). Urethral stricture requiring dilatation has developed in 

4.5% (16/357) of patients. Urinary stress incontinence has occurred in 3.4% 

(12/357). RTOG late bladder toxicities were : 0% Grade 4, 0% Grade 3, and 

3.4% (12/357) Grade 2. RTOG late rectal toxicities were : 0.3% (1/357) Grade 

4, 0% Grade 3, 3.1% (11/357) Grade 2, and 3.6% (13/357) Grade 1. RTOG 

late rectal toxicity was higher in patients undergoing HDR + IMRT with 15.6% 

(17/109) of patients experiencing Grade 2 and 1 symptoms, vs. 2.8% (7/248) 

receiving HDR alone (p < 0.0001). 

Conclusions: We have observed no significant difference in PSA disease 

free survival in patients undergoing HDR monotherapy vs. HDR + IMRT. 

Complications were similar, though RTOG Grade 1 and 2 late toxicity was 

higher in patients receiving HDR + IMRT. HDR monotherapy compares favorably 

to EBRT, LDR +/- EBRT, and HDR + IMRT, both with regard to PSA 

disease free survival, and complications. With regard to implant technique, 

HDR brachytherapy offers other advantages over LDR, such as no radiation 

exposure to hospital personnel, no seed migration, greater dose flexibility and 

precision of radiation dose delivery. Larger volumes can be treated with HDR. 

By omitting EBRT, rectal complications may be reduced. 

328 oral 

S 107 

BRACHYTHERAPY, EXTERNAL BEAM RADIOTHERAPY AND 

RADICAL PROSTATECTOMY: COMPARISON OF THE IMPACT 

ON HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH 

LOCALIZED PROSTATE CANCER 2 YEARS AFTER TREATMENT 

F. Guedea 1 , J. F. Suárez 2 , M. Ferrer 3 , F. Ferrer 1 , A. Boladeras 1 , J. Pera 

1 , M. Ventura 1 , V. E. Padín 1 , F. Aguiló 2 

1 

INSTITUT CATALÀ D’ONCOLOGIA, Oncología Radioterápica, L’Hospitalet de 

Llobregat, Spain 

2 

HOSPITAL UNIVERSITARI DE BELLVITGE, Urología, L’Hospitalet de 


3 

IMIM-HOSPITAL DEL MAR, Unidad de Investigación en Servicios Sanitar- 

ios, Barcelona, Spain 

Purpose: To compare the effect of treatment on health-related quality of life 

(HRQL) in patients with localized prostate cancer from before treatment to 2 

years postintervention. 

Materials: This was a prospective, longitudinal study of 304 patients treated 

at the Catalan Institute of Oncology and the University Hospital of Bellvitge 

in Spain for localized prostate cancer. Patients underwent radical prostatectomy 

(114 patients), 3D external conformal radiotherapy (134), or brachytherapy 

(56). The HRQL questionnaires administered before and after treatment 

(months 1, 3, 6, 12, 24) were the Medical Outcomes Study 36-item 

Short Form, the Functional Assessment of Cancer Therapy (General and 

Prostate Specific), the Expanded Prostate Cancer Index Composite (EPIC), 

and the American Urological Association Symptom Index. Differences between 

groups were tested by analysis of variance. Generalized estimating 

equations (GEE) models were constructed to assess between-group differences 

in HRWL at 2 years of follow-up after adjusting for clinical variables. 

Results: In each treatment group, HRQL initially deteriorated after treatment 

with subsequent partial recovery. However, the score on some domains were 

still significantly lower 2 years after treatment. GEE models showed that, 

compared to the brachytherapy group, radical prostatectomy patients had 

worse EPIC sexual summary and urinary incontinence scores (-18.74 and 

11.45; P


or intermediate risk disease (GS=7 or PSA 10-20ng/mL) had 5 year bRFS of 

100 % compared to 43 % for those with high risk disease (GS>=8 or PSA>20 

ng/mL or GS=7 with PSA 10-20 ng/mL) (p=0008.) Patients with PNI had 

nearly identical 5-year bRFS to those without PNI, 67% and 71 %, respectively 

(p=0.57). 

Conclusions: In our population nearly 1 in 7 patients with presumed T1 ot T2 

disease actually had occult T3b disease. Even among patients with GS


compared with corresponding DVHs resulting from our previous two-phase 

sequential conformal technique that delivered 60 Gy to the bladder and 46 

Gy to the pelvic lymph nodes. To evaluate the conformity, the Dice Similarity 

Coefficient (DSC) was calculated at 95 % dose level for the PTV (bladder). 

Calculations of the generalised Effective Uniform Dose (gEUD) were also performed 

for the bowel (reference volume of 200 cm3 and a = 4) and the rectum 

(a = 12). 

Results: Using IMRT, we obtained a significant normal tissue sparing as 

well as a highly conformal treatment of the bladder. For the bowel, a significant 

volume reduction was obtained at all dose levels between 20 and 50 Gy 

(p


335 oral 

TREATMENT PLAN INTERCOMPARISON BETWEEN RAPIDARC 

AND HELICAL TOMOTHERAPY FOR SELECTED PEDIATRIC CASES 

WITH SIB REGIME. 

A. Fogliata Cozzi 1 , G. Nicolini 1 , E. Vanetti 1 , A. Clivio 1 , S. Yartsev 2 , L. 

Cozzi 1 


2 LONDON REGIONAL CANCER CENTRE, Medical Physics, London, Canada 

Purpose: The potential benefits and limitations of the new volumetric intensity 

modulated arc therapy (RapidArc, RA) from Varian and of the Helical 

Tomotherapy (HT) were investigated on five paediatric patients. RA offers a 

combined planning and delivery method based on an arc where multileaf collimator, 

dose rate and gantry speed are optimised simultaneously to achieve 

the needed degree of modulation. RA is based on direct aperture field optimisation, 

with the aim to reduce delivery time and to minimise MU/Gy needed. 

Materials: The same image and structure sets of five paediatric patients were 

used to design RA and HT plans. The tumour types included a Ewing sarcoma, 

a rhabdomyosarcoma, a metastatic rhabdomyosarcoma, a liver metastasis 

of Wilm’s tumour, and brain metastasis from a nefroblastoma. Four 

cases were planned with SIB at two prescription dose levels to the targets 

depending on the case. DVHs of the targets were evaluated as the ratio between 

corresponding parameter values from RA and HT plans. Fot the PTVs, 

analysed parameters were: D2, D98 (as maximum and minimum significant 

doses), D5-D95 to evaluate the dose homogeneity in the target. Organs at 

risk (OAR) DVHs were evaluated case by case, and results were presented 

as the difference of the analysed parameter in RA and HT plans. 

Results: Over all our cases, no significant difference was found in 

the average RA/HT ratios for the PTV with lower prescription level: 

D2RA/HT=0.995±0.035; D98RA/HT=0.996±0.042. Dose coverage was 

slightly better for the PTV with higher prescription: D2RA/HT=0.984±0.035; 

D98RA/HT=0.979±0.020. Homogeneity parameters for all PTVs, averaged 

over all the patients, were D5-D95=3.9±1.4 Gy for RA, 3.0±1.1 Gy for HT 

plans. Mean doses to the OARs and maximum dose for the spinal cord were 

computed. Average on the mean OARRA-HT dose difference was better for 

RA (-1.7±4.9 Gy), while the maximum dose to the spinal cord was lower in 

HT plans: 4.2±5.5 Gy. The healthy tissue mean dose (the dose bath) was 

larger for HT in all cases with average value for the difference of -1.5±0.9 Gy. 

Conclusions: Both RA and HT provided good target coverage and OAR 

sparing with potential impact on patients with long life expectancy.


Physics aspects of Hadron therapy 

336 oral 

CARBON ION BOOST AND IMRT: SEQUENTIAL VS. SIMULTANE- 

OUS INTEGRATED BOOST 

M. C. Frese 1 , J. Wilkens 1 , A. Jensen 2 , U. Oelfke 1 

1 GERMAN CANCER RESEARCH CENTER (DKFZ), Department of Medical 

Physics in Radiation Oncology, Heidelberg, Germany 

2 UNIVERSITY OF HEIDELBERG, Department of Radiation Oncology, 


Purpose: A clinical application of carbon ions in radiotherapy is their use as 

a sequential boost irradiation for a photon IMRT plan. The two respective 

treatment plans are usually optimized separately and the sum is calculated in 

terms of the photon equivalent dose. New treatment centres with carbon ion 

and photon beams in close proximity could allow for a treatment with carbon 

ions and photon IMRT within the same fraction. This requires simultaneous 

optimization of both treatment plans to account for the biological effect of both 

modalities at the same time. 

Materials: We developed a method for biological optimization for ion and 

photon therapy based on the linear-quadratic model for the biological effect. 

The method was implemented in our treatment planning system KonRad and 

allows for different radiation modalities in the same plan. To investigate the 

impact of simultaneous optimization two clinical cases containing a high-dose 

boost volume (PTV1) and a surrounding low-dose target volume (PTV2) were 

optimized for four different treatment strategies with 30 fractions: IMRT with 

integrated boost (photons only), photon IMRT for PTV2 with a sequential carbon 

ion boost, photon IMRT with a simultaneous integrated carbon ion boost 

for all fractions and finally a combination where the integrated carbon boost 

is delivered only for 10 fractions and additionally IMRT only for PTV2 for 20 

fractions. The carbon ion irradiation was aimed at PTV1 only. All cases were 

optimized for the same prescribed doses in PTV1 (66 CGE) and PTV2 (54 

CGE). 

Results: As expected all plans incorporating carbon ions improved the sparing 

of normal tissues compared to the mere photon IMRT plan. The two plans 

with the integrated carbon ion boost showed a reduced overdosage of PTV2 

compared to the other two treatment strategies. Best results were achieved 

with treatment plans using photon IMRT with a simultaneous carbon ion boost 

for all fractions. However, comparable plan quality was achieved using an integrated 

carbon ion boost only for ten fractions and for the other fractions only 

IMRT. 

Conclusions: Simultaneously optimized IMRT plans with an integrated carbon 

ion boost result in reduced overdosage of the PTV2 and normal tissue. 

Treatment with a combined photon and carbon plan for all fractions is 

favourable, but the slightly reduced plan quality if a simultaneous integrated 

boost is only applied for 10 fractions is acceptable bearing in mind that this 

strategy reduces the treatment effort. 

337 oral 

PARTICLE THERAPY APPEARS TO BE A COST-EFFECTIVE 

TREATMENT MODALITY AS OPPOSED TO CONVENTIONAL 3D 

RADIOTHERAPY AND STEREOTACTIC BODY RADIOTHERAPY 

FOR INOPERABLE STAGE I NON-SMALL CELL LUNG CANCER 

PATIENTS, BUT MORE EVIDENCE IS NEEDED 

J. Grutters 1 , M. Pijls-Johannesma 1 , M. Joore 2 , D. De Ruysscher 1 , A. 

Dekker 1 , A. Peeters 1 , S. Reimoser 3 , J. Severens 4 , P. Lambin 1 

1 MAASTRO CLINIC, Radiation Oncology , Maastricht, Netherlands 

2 UNIVERSITY HOSPITAL MAASTRICHT, Department of Clinical Epidemiology 

and Medical Technology Assessment, Maastricht, Netherlands 

3 TURNER & TOWNSEND GMBH, Munchen, Germany 

4 MAASTRICHT UNIVERSITY, Department of Health Organization, Policy 

Economics, Maastricht, Netherlands 

Purpose: Particle therapy with protons or carbon-ions is a promising treatment 

modality for non-small cell lung cancer (NSCLC). However, the initial 

investment for particle therapy is high, and it is unclear whether the potential 

extra effects are worth the extra costs. Therefore, the cost-effectiveness 

of particle therapy as opposed to conventional 3D radiotherapy (3DRT) and 

stereotactic body radiotherapy (SBRT) for inoperable stage I NSCLC patients 

was examined. 

Materials: A Markov model was constructed with four health states regarding 

survival and irreversible adverse events. In the absence of comparative studies, 

modelling is a solution to synthesize available evidence. The health care 

costs and effects on survival of 3DRT, SBRT, proton therapy and carbon-ion 

therapy for a cohort of inoperable stage I NSCLC patients were compared 

over a five-year time horizon. Transition probabilities were derived from publications 

of centres worldwide with longstanding experience in particle or photon 

radiotherapy using a systematic review. 

Results: Preliminary results showed that the expected total health care costs 

per patient for SBRT were e531 higher than 3DRT and that SBRT yielded 

1.03 more life-years than 3DRT (Figure 1), resulting in an incremental costeffectiveness 

ratio (ICER) of e517 per life-year gained. Proton therapy was 

S 111 

e2517 more expensive than SBRT and yielded 0.44 extra life-years, resulting 

in an ICER of e5660 per life-year gained. Carbon-ion therapy was e2970 

more expensive and yielded 0.05 extra life-years compared to proton therapy, 

resulting in an ICER of e58.386 per life-year gained. 

Conclusions: These preliminary results indicate that particle therapy is a 

cost-effective treatment modality for inoperable stage I NSCLC patients. However, 

the results should be interpreted with caution, as the differences between 

the different treatment modalities are small and surrounded by large 

uncertainty. More analyses will be performed of which the results will be presented 

at the conference. First, probabilistic sensitivity analyses will be used 

to reflect uncertainty in de model parameters. Second, particle therapy is 

expected to improve quality of life. Therefore quality of life weights will be 

collected for the different health states in order to allow for the calculation of 

costs per quality adjusted life year (QALY) gained. It is expected that this will 

result in a lower ICER of carbon-ion therapy as opposed to proton therapy. 

Third, particle therapy may be more cost-effective in different patient populations, 

i.e. operable stage I patients or stage III NSCLC patients. Therefore the 

cost-effectiveness of particle therapy will also be assessed for these populations. 

Finally, expected value of perfect information (EVPI) analyses will be 

presented in order to support decisions regarding the investment in further 

research. 

338 oral 

PROTON RADIOGRAPHY FOR CLINICAL APLLICATION 

C. Talamonti 1 , V. Reggioli 1 , L. Marrazzo 1 , M. Bruzzi 2 , M. Bucciolini 1 , M. 

Patterson 3 , H. Sadrozinski 3 , V. Bashkirov 4 , R. Schulte 4 , N. Randazzo 5 , 

V. Sipala 5 , P. Cirrone 6 

1 

UNIVERSITY OF FLORENCE AND INFN SEZIONE DI FIRENZE, Clinical 

Physiopathology, Florence, Italy 

2 

UNIVERSITY OF FLORENCE AND INFN SEZIONE DI FIRENZE, Energetic, 

Florence, Italy 

3 

SANTA CRUZ INSTITUTE FOR PARTICLE PHYSICS, UC Santa Cruz- CA, 

USA 

4 

LOMA LINDA UNIVERSITY MEDICAL CENTER, Loma Linda, USA 

5 

INFN SEZIONE DI CATANIA, Catania, Italy 

6 

INFN LABORATORI NAZIONALI DEL SUD, Catania, Italy 

Purpose: Proton imaging is not yet used in the clinical routine, although the 

advantages of this technique have been extensively demonstrated. In the 

context of quality assurance in proton therapy, proton images can be used 

to verify the correct positioning of the patient and to control the range of the 

protons. Proton Computed Tomography (pCT) is also the most appropriate 

imaging method to perform planning and verification of proton based radiation 

treatments, since it permits to evaluate the distribution of proton stopping 

power within the tissues. The PRoton IMAging project, founded by INFN and 

MIUR (Italy), aims to realize a proton Computed Radiography (pCR) system 

and finaly a pCT system. A preliminary experience about this subject has 

been acquired in previous experiments performed at the medical proton synchrotron 

located at Loma Linda University Medical Centre (LLUMC). In particular 

this work constitutes a valuable knowledge in data reconstruction and 

simulation for PRIMA project. 

Materials: In this work the results of the last LLUMC experiment are reported. 

The experimental set-up consists of telescopes of silicon strip detectors at 

the entrance and exit of a phantom and of a CsI crystal calorimeter to measure 

the proton energy loss (Fig.1).The telescope makes use of the silicon 

planes, each of the four x-y planes consists of two single silicon strip detector 

(SSD), with their strips crossing at 90 degree. While with a pitch of 

the SSD of 236 µm the position resolution is 68 µm, the performance of the 

system is determined by multiple Coulomb scattering (MCS). For example, 

the MCS in one x-y plane amounts to about 3 mrad for 200 MeV protons, 

similar to the directional precision of the telescopes with 3 cm separation between 

planes. The calorimeter consists of single crystals of doped CsI of 12 

cm length, sufficient to stop 200 meV protons. The low-contrast segmented 

phantom consists of an array of 12 1" plates of tissue equivalent plastic, e.g. 

Poly(methyl methacrylate) PMMA, tightly stacked along the beam direction. 

The 6th plate contains a pattern of holes of varying diameters and depth, and 

was removable to calibrate the overall density of the stack. 

Results: In Fig 2 is shown the radiography of the 6th plate without applying 

any correction for MCS. The image is reconstructed by defining a 2D grid


of two strips pixel. The mean energy is then plotted on the grid resulting 

in the proton image of the phantom. To measure the spatial resolution of 

the system, a commercial QC-3 phantom was used. It consists of groups 

of high contrast bar patterns with spatial frequencies in the range 0.1-0.7 

lp/mm. The patterns comprise alternate plates of lead and plastic. There are 

also some regionswith uniform absorbers. In Fig 3 the reconstructed image 

is plotted.These images yield information on the realistic dose dependence 

of contrast and resolution. 

Conclusions: We have report the results of a beam experiment to develop 

proton computed tomograpy. we have imaged a low contrast phantom inside 

a stack of PMMA plate by reconstructing the mean outgoing energy of each 

image pixel. Even if no correction is applied it is possible to distinguish 6 mm 

of thickness over 15 cm and in the region of higher statistic it is possible to 

resolve holes of 1mm diameter. The QC3 radiography shows the central part 

of the phantom and without corrections we can distinguish the bar patterns 

with spatial frequencies 0.25 lp/mm and 0.45 lp/mm. 

339 oral 

PATIENT SPECIFIC RESPIRATORY MOTION PROBABILITY DEN- 

SITY FUNCTION CONVOLVED DOSE DISTRIBUTION FOR PROTON 

THERAPY OF LUNG CANCER 

L. Zhao 1 , G. Sandison 1 , J. Farr 2 

1 PURDUE UNIVERSITY, School of Health Sciences, West Lafayette, USA 

2 WESTDEUTSCHES PROTONENTHERAPIEZENTRUM ESSEN GGMBH, Essen, 

Germany 

Purpose: To predict the dose distribution for moving targets and surrounding 

normal tissues by convolving a static dose distribution with a patient specific 

respiratory probability density function that describes the nature of the motion 

for proton therapy of lung cancer. 

Materials: Four dimensional computed tomography (4D-CT) scans of a dynamic 

thorax phantom (CIRS Model 008) and a representative lung cancer 

patient were acquired to quantify tumor motion trajectories. The centroids of 

the targets were calculated after contouring over all 10 phases of the 4D-CT 

scan on the CMS XiO R○Treatment Planning System. The patient specific 

respiratory probability density functions in the bin of 1mm were obtained by 

interpolating with a cubic-spline function. The static dose distribution calculated 

from the treatment planning system and the patient specific respiratory 

probability density function were input into in-house developed software to 

implement dose convolution. The static dose distribution and the convolved 

dose distribution were compared in a commercial dosimetry analysis package 

(OmniPro I’mRT). 

Results: An analysis of the dose maps showed that the maximum dose difference 

between the static dose and the convolved dose was 29% and 16% of 

the prescribed dose (70Gy) in the phantom and the patient, respectively. Figure 

1displays the static dose map and the patient respiratory motion probability 

density function convolved dose map of the phantom in the coronal isocentric 

plane.Figure 1: 2D Dose maps of the phantom in the coronal isocentric 

plane. (a) Static dose. b) Patient specific respiratory motion probability density 

function convolved dose map. 

Conclusions: Direct incorporating patient specific respiratory motion probability 

density function into dose calculation can effectively predict the dose to 

the lung tumor and normal structures, which provides a potential solution to 

the limitations of the PTV concept in proton therapy.


340 oral 

ROBUSTNESS ANALYSIS STUDY IN FRACTIONATED PROTON 

RADIOTHERAPY 

C. Negreanu 1 , O. Stadelmann 1 , A. Lomax 1 

1 PAUL SCHERRER INSTITUTE, Centre for Proton Radiotherapy, Villigen - 

PSI, Switzerland 

Purpose: A robust radiation treatment planning achieves a good agreement 

between treatment dose and prescription. Current practice uses conventional 

static margins to account for uncertainties, but overdosing of nearby normal 

tissue may result, however, in increased toxicity in patients. Moreover, for 

proton radiation therapy (PT), the effects of such uncertainties can potentially 

occur well within the target volume, due to the effects of misaligned density 

heterogeneities. In order to attain the best compromise between tumor 

control and risk of normal tissue complications, the assessment of the PT 

treatment plans and their robustness to both spatial and range uncertainties 

is proposed. 

Materials: An error analysis tool, developed to simultaneously process any 

number of ’error’ dose distributions (recalculated doses considering various 

PT uncertainties), has been used to analyze single field and full plan dose 

distributions. The single fields have been categorised using a ’heterogeneity 

index’ (HI), whereby the density heterogeneities seen by a field are combined 

into a single value. The lower HI, the more homogenous the anatomy through 

which the field passes. Plan robustness has been assessed by combining all 

error dose distributions using a normal probability distribution function, with 

the resulting distributions being analysed using gamma-index distributions 

(compared to the nominal plan) and the changes in D98 values to the CTV 

(deltaD98). Random spatial errors of 2 and 4mm and systematic range uncertainties 

of +/-3% have been analysed, together with the effect of varying 

PTV margins from 2-5mm. 

Results: A clustering effect for the gamma-index distribution as a function 

of deltaD98 is observed for various HI. An example is given in the figure, 

where the percentage of points with a gamma-value > 1 (acceptance criterion, 

3%/3mm) is plotted against deltaD98 for a number of fields. Fields with large 

HI values (>25, shown in red) clearly show higher gamma-values, and a slight 

shift to larger deltaD98, implying that density heterogeneities have an effect 

throughout the target, but less of an effect on target coverage. Varying the 

PTV margin generally reduces the deltaD98, but has a smaller effect on the 

gamma-analysis. Similar analysis applied to full plans shows, although case 

dependent, considerable differences between plans calculated using fields 

with large HI against those with fields with small HI. This indicates that our HI 

could still be fine tuned somewhat. Range uncertainty analysis showed that 

only 3% undershoots have an effect on CTV coverage, and mainly reduce the 

D98. 

Conclusions: The role of the systematic and random errorrs on treatment 

plans for various tumor sites has been assessed for various PTV margins. 

This analysis is currently being extended to include rotations.Fig.: Gammaindex 

map for 3mmPTV margins and 2mm standard deviation as a function 

of the deltaD98 for various HI. 

341 oral 

MONTE CARLO STUDIES OF SECONDARY DOSES FROM TREAT- 

MENT OF PROSTATE CANCER WITH LIGHT IONS 

I. Gudowska 1 , M. Hultqvist 1 

1 KAROLINSKA INSTITUTET AND STOCKHOLM UNIVERSITY, Medical 


Purpose: In light ion beams, secondary particles are produced both in the 

beam line and in the patient. These particles include neutrons, protons and 

heavier fragments and deliver dose both to the tumour and normal tissues. 

In addition, dose to tissues close to the target can be delivered by scattered 

S 113 

primary particles. Unwanted damage can thus be inflicted and the risk for 

radiation induced secondary cancers arises. 

Materials: Due to the very complex interaction pathways of high energy 

and heavy charged ions transported in the patient, 3-D Monte Carlo particle 

transport codes provide a unique and very useful tool in the prediction of 

the physical radiation doses to organs. In the present work the mathematical 

anthropomorphic phantom ADAM-HIT, based on the adult male phantom 

from the ORNL Mathematical Phantom Series, was applied in the Monte 

Carlo code SHIELD-HIT for simulations of prostate irradiations with 1 H, 7 Li 

and 12 C ion beams. The doses to healthy organs delivered by scattered primaries 

and secondaries produced in the phantom, the energy spectra and 

LET-distributions of these particles were studied. Careful analysis of the dose 

distribution in the rectum was performed by the implementation of a more detailed 

geometrical structure of this organ. 

Results: The secondary doses to healthy organs are in the order of 10 -10 - 

10 -4 of the dose to the target (prostate) and decrease with distance from the 

target. Protons in the LET-interval 0-5 eV/nm contribute most to the secondary 

doses in all organs and for all beams. Heavier secondary ions (from 

He to Ca) have LET values up to 3000 eV/nm and have larger dose contributions 

in the ion beams of larger atomic number Z. In general the organ dose 

per target dose increases with increasing Z of the primary particle; however, 

for lighter primary ions (Z≤3) and for organs close to the prostate, such as 

the rectal wall (about 1 mm distance), scattered primary particles show nonnegligible 

dose contributions. In the case of full rectal filling, the percentage 

of the total dose to the rectal wall that is due to protons is 99 % for the 1 H 

beam, 80 % for the 7 Li beam and 87 % for the 12 C beam, and the percentages 

due to Li-ions are 0.01 %, 2 % and 0.4 %, respectively. These numbers 

indicate dose contributions from scattered primaries. 

Conclusions: The secondary doses contribute mainly to the organs close 

to the irradiated volume and the dominating secondary particles are protons. 

In the rectal wall, the total dose per target dose is similar for the different 

beams. Although the production of secondaries increases with Z, the dose 

contribution from scattered light primaries even out the difference. The RBE 

of particles delivering secondary doses need to be considered when estimating 

the risk of induction of secondary tumours. 

Dose Calculation 

342 oral 

DOSE CALCULATION FOR PROTON RADIOTHERAPY BASED-ON 

MONTE CARLO SIMULATION USING ANATOMICAL DETAILED 

HUMAN MODEL 

B. Guo 1 , Y. Liu 1 , C. Shi 1 , P. Mavroidis 2 , C. Ha 1 , G. Xu 3 , N. Papanikolaou 

1 

1 

UNIVERSITY OF TEXAS, CANCER THERAPY & RESEARCH CENTER, 

Radiation Oncology, San Antonio, USA 

2 

KAROLINSKA INSTITUTET AND STOCKHOLM UNIVERSITY, Stockholm, 

Sweden 

3 

RENSSELAER POLYTECHNIC INSTITUTE, Department of Mechanical, 

Aerospace, and Nuclear Engineering , Troy, New York, USA 

Purpose: The need for high dose accuracy has long been an issue since 

the complexity of human body and the complex treatment planning. In this 

work, we aim to build an accurate dose calculation algorithm based on human 

anatomy-based model using Monte Carlo simulation for providing basic and 

benchmarking data for therapeutic protons. 

Materials: Both phantom-based and human anatomy-based models were 

used. The human anatomy model was developed from Visible Human Project 

(VHP R○) at National Library in Medicine (NLM). VHP project created a set 

of complete, anatomically detailed, three-dimensional representations of the 

normal human bodies. The human anatomy-based model, named as VIP- 

Man, was built with 4 mm x 4 mm x 4mm voxel resolution with total over 6 

million voxels for describing the whole body, as Figure 1 (a-d). Each voxel 

was assigned physical properties, including density and isotopic composition. 

The Los Alamos National Library developed Monte Carlo code, MCNPX, 

was used to simulate the transport and energy deposit to each voxel. An 

in-house dosimetry software package, Human Anatomy-based Monte Carlo 

Dose (HAMD) was developed to analysis the huge dose dataset based on 

Monte Carlo simulation and the three dimensional dose matrix was super 

positioned to the CT image correspondingly. 

Results: The Monte Carlo simulation provided very close agreement to the 

two widely used proton range-energy tables with the average depth peak difference 

less than 0.70% and 0.37%, the maximum difference less than 1.17% 

and 1.15% to ICRU Report 49 and Janni Data nuclear data table (DNDT) respectively 

from 40 MeV to 250 MeV energy range.HAMD performed very accurately 

in proton treatment dose calculation. HAMD offers very friendly and 

familiar interface for physicians to conveniently review a treatment plan. The 

isodose lines in transverse, sagittal and coronal views provided very conformal 

coverage to the contours in lung, as Figure 1 (e-f). 

Conclusions: The simulated proton range-energy table has been accurately 

benchmarked compared to two independent dataset of measurements. The 

in-house developed dose algorithm HAMD performs very well in dose calculation 

both in phantom-based and human anatomy-based heterogeneity. The


HAMD needs further validation by using additional human anatomy-based 

models and specified beam source configuration. The long-term and board 

objective is to provide an extreme accurate dose calculation based on human 

model for benchmarking clinic treatment planning systems. 

343 oral 

FAST PENCIL KERNEL DOSE CALCULATIONS FOR PHOTON 

BEAMS USING INTERPOLATION IN THE PENCIL KERNEL PARAM- 

ETER SPACE 

D. Eriksson 1 , A. Ahnesjö 1 

1 NUCLETRON SCANDINAVIA AB, Klostergatan 12, SE-751 47 , Uppsala, 

Sweden 

Purpose: In modern radiotherapy there is a need for fast pencil kernel dose 

calculation, although more accurate but slower algorithms exist. Fast dose 

calculations can drive IMRT optimizations to refined objectives or facilitate 

multiple calculations for simulation of setup uncertainties.Pencil kernel dose 

calculations are based on a convolution of the kernel with the beam energy 

fluence, which can be calculated very fast for lateral planes using FFT technique. 

Lateral dose distributions can be used together with interpolation along 

the depth dimension to reduce calculation time. Parameterization of pencil 

kernels have been published, which raise the issue if more effective interpolation 

schemes can be constructed using the parameter domain instead of 

the depth dimension. 

Materials: We use the pencil kernel parameterization given through Eq. (1), 

where Az, az, Bz and bz are depth dependent parameters, ρ the mass density, 

r the cylindrical radius and z the calculation depth. The first term represent 

the primary dose component and the second term the scatter dose. 

The primary dose interpolation was done using Eq. (2),where l and h are the 

depths for which explicit convolutions are performed, Sl , Sh and Sz are the 

beam axis distances to l, h, and z, respectively, Siso is the isocenter distance, 

ψl and ψh are the energy fluencies in air projected at l and h. The scatter 

dose is interpolated analogously.The selection of the convolution planes were 

optimized for 56 different treatment units ranging from 60Co to 50 MV to minimize 

dose errors and correlating the result to their respective TPR20,10 values. 

The resulting algorithm was implemented into a commercial treatment 

planning system, Oncentra R○MasterPlan v3.1 as Enhanced Pencil Beam. 

Results: We found that two depths for the primary dose and three depths for 

the patient scatter dose were sufficient. The locations of the required planes 

were well correlated with the TPR20,10 index, see Figure 1. The largest 

differences were found in the build-up penumbra region, considered to be of 

minor relevance. Calculation speed improvement was 4 to 8 times compared 

to MasterPlan v3.0. 

Conclusions: We have shown that lateral dose interpolation can be efficiently 

performed in the kernel parameter space to facilitate fast dose calculations. 

Figure1. Correlation between the optimized locations of the two 

convolution planes for the primary dose, relative to the kernel max amplitude 

depth, and the TPR20,10 index for the 56 treatment units. 

344 oral 

VERIFICATION OF MONTE CARLO DOSE CALCULATIONS IN AN 

ANTHROPOMORPHIC THORAX PHANTOM FOR CYBERKNIFE 

TREATMENT OF SMALL LUNG TUMOURS. 

H. Marijnissen 1 , M. Hol 1 , P. van der Baan 1 , B. Heijmen 1 

1 ERASMUS MC, Radiotherapy, Rotterdam, Netherlands 

Purpose: The purpose of this dosimetry study is to establish the accuracy 

of dose calculations for Cyberknife treatment of small lung tumors, performed 

with the Monte Carlo Dose Calculation Algorithm in Multiplan. Monte Carlo 

calculations are compared with phantom measurements and predictions with 

the simpler Ray-Tracing Dose Calculation Algorithm also in MultiPlan. 

Materials: Measurements for commissioning of the Monte Carlo dose calculation 

engine consisted of measurement of Output Factors in air, pdd for 

the 60 mm cone and a beam profile measurement without cone. Verification 

measurements were performed in slab phantoms and in a newly constructed 

anthropomorphic thorax phantom. The applied water-, lung- and bone equivalent 

phantom materials (Gammex RMI) are well specified for Monte Carlo


modeling. The modular thorax phantom can be equipped with Solid Water 

lung tumours of 10, 20 or 30 mm in diameter, embedded in the lung tissue 

equivalent material. Measurements were mainly performed with Gafchromic 

EBT film, complemented with single point stereotactic diode and pinpoint ionization 

chamber (PTW) in additional water phantom experiments. Gafchromic 

EBT film allows precise and rapid measurement of absolute dose and dose 

distribution as also confirmed in this study. For cones of 5, 10, 20 and 

60mm, single beam experiments were done for various slab phantoms. For 

the thorax phantom, multi-beam treatments were performed, simulating a patient 

treatment. The absolute dose and dose distribution was measured with 

Gafchromic EBT film in a plane through the center of the lung tumour. 

Results: Gafchromic EBT film measurements and Monte Carlo calculations 

for single beam irradiations of the homogeneous Solid Water slab phantom 

were in excellent agreement with water phantom measurements using the 

diode and pinpoint ionization chamber, as well as with ray-tracing dose calculations. 

This proved that (1) our beam data was correctly modelled in the 

Monte Carlo TPS, and (2) the Gafchromic EBT film was suitable for further 

experiments. For the inhomogeneous slab phantoms, Monte Carlo calculated 

absolute lung doses generally agreed within 3% with measurements, even for 

the smallest cones. Also for beam profiles and depth dose curves excellent 

agreement with measurements was observed. For the 3 solid lung tumours 

in the thorax phantom, MultiPlan isocentric treatment plans were compared 

with Monte Carlo and Gafchromic EBT film results. The agreement between 

Monte Carlo and Gafchromic EBT film was within the expected experimental 

error, while considerable discrepancies between measurements and raytracing 

dose calculations were observed. 

Conclusions: Monte Carlo and Gafchromic EBT film measurements in inhomogeneous 

(anthropomorphic) phantoms were in very good agreement. 

For treatment of (small) lung tumours the Monte Carlo is the preferred dose 

calculation engine. 

345 oral 

DOSIMETRIC VERIFICATION OF RADIOTHERAPY TREATMENT 

PLANNING SYSTEMS: RESULTS OF IAEA PILOT STUDY 

E. Gershkevitsh 1 , R. Schmidt 2 , G. Velez 3 , D. Miller 4 , E. Korf 5 , F. Yip 6 , 

S. Wanwilairat 7 , S. Vatnitsky 8 

1 

NORTH ESTONIA REGIONAL HOSPITAL, Radiotherapy, Tallinn, Estonia 

2 

UNIVERSITY MEDICAL CENTRE EPPENDORF, Radiotherapy and Radiobiology, 

Hamburg, Germany 

3 

CABIN, Radiotherapy, Chubut, Argentina 

4 

LOMA LINDA UNIVERSITY MEDICAL CENTER, Loma Linda, USA 

5 

SOUTHERN CROSS HOSPITAL, Radiotherapy, Cape Town, South Africa 

6 

INSTITUTE OF ONCOLOGY AND RADIOBIOLOGY, Radiotherapy, La Habana, 

Cuba 

7 

CHIANG MAI UNIVERSITY HOSPITAL, Radiotherapy, Chiang Mai, Thailand 

8 

INTERNATIONAL ATOMIC ENERGY AGENCY, Medical Physics and Dosime- 

try, Vienna, Austria 

Purpose: The methodology developed by IAEA for dosimetric quality control 

of treatment planning systems has been tested in different hospitals through 

a pilot study. The aim was to verify the methodology and observe the range of 

deviations between planned and delivered doses in 3D conformal radiotherapy 

in situations close to clinical setting. 

Materials: The methodology is based on anthropomorphic phantom representing 

the human thorax and simulates the whole chain of external beam 

radiotherapy treatment planning activities. The phantom is scanned using 

computed tomography and eight test cases are planned on treatment planning 

system which simulate different irradiation geometries found in conformal 

radiotherapy. The doses were measured with ion chambers and deviation 

between measured and treatment planning system calculated doses were reported. 

This methodology was tested in 17 different hospitals which are using 

14 different algorithms/inhomogeneity correction methods implemented in different 

treatment planning systems. 

Results: A total of 53 clinical test case datasets for different energies and 

calculation algorithms have been produced. Most of the systems with advanced 

algorithms complied with predefined agreement criteria. The dose 

differences more than 20% were discovered for some of simple algorithms 

and high energy X-ray beams. The number of deviations outside agreement 

criteria increases with the beam energy and decreases with advancement of 

treatment planning system calculation algorithms. 

Conclusions: Large deviations exist in some simple dose calculation algorithms, 

therefore more advanced algorithms would be preferable and therefore 

should be implemented in clinical practice. The test cases that could be 

performed in reasonable time would help the user to appreciate the possibilities 

of their system and understand its limitations. 

346 oral 

S 115 

MONTE-CARLO DOSIMETRY FOR STEREOTACTIC SYN- 

CHROTRON RADIATION THERAPY (SSRT) FOR BRAIN TUMORS 

Y. Prezado Alonso 1 , J. F. Adam 2 , A. Bravin 1 , M. Edouard 3 , H. Ellaume 3 , 

F. Esteve 3 , C. Nemoz 1 , M. Renier 1 

1 

EUROPEAN SYNCHROTRON RADIATION FACILITY, Biomedical Beamline 

ID17, Grenoble, France 

2 

UNIVERSITÉ JOSEPH FOURIER, Grenoble, France 

3 

INSERM U647, Grenoble, France 

Purpose: High-grade glioma are still of poor prognostic value. Radiotherapy 

of such tumors requires high doses, whereas the tolerance of healthy brain 

tissues limits the maximum deliverable dose. A local dose enhancement can 

be obtained in brain tumors after infusion of an iodinated contrast agent and 

irradiation with kilovoltage X-rays. Preclinical trials using iodinated contrast 

agents have shown a significant extension of the life span in treated tumorbearing 

animals (J.F. Adam et al, Int. J. Radiation Oncology Biol. Phys. 64 

(2006) 603). In the perspectives of phase I-II clinical trials, the aim of this 

study is to assess the dosimetric properties of the Stereotactic Synchrotron 

Radiotherapy (SSRT), when the irradiation is done from several entrance angles. 

SSRT delivered with a continuous arch has already been studied (C. 

Boudou et al., Phys. Med. Biol. 50 (2005) 4841). 

Materials: Monte-Carlo is considered the state-of the art method in radiation 

physics calculations. The PENELOPE code has been used to determine the 

dose distributions in a head phantom ( O.K .Harling et al., Med Phys. 22 

(1995) 579) to assess the doses. Nine beams irradiating the head from different 

entrance angles have been simulated. A theoretical cylindrical tumor of 

different sizes, loaded with different iodine concentrations was included in the 

calculations. Several simulations considering different positions of the tumor 

inside the brain were performed. 

Results: The presence of iodine in the tumor increases the deposited dose in 

the tumor, and therefore the therapeutic effect, by a factor depending on the 

iodine concentration. The enhancement factors for different iodine concentrations 

will be here presented. In addition, the simulations show that the dose to 

the bone remains within tolerance whereas that received by the healthy brain 

tissues is significantly lower in average than in conventional radiotherapy. The 

dose distribution for the different positions, sizes of the tumor as well as for 

several iodine concentrations will be presented. The average doses received 

by the organs at risk will be discussed. 

Conclusions: This study demonstrates that SSRT treatments with a discrete 

number of entrance angles result in an enhancement factor of the dose deposited 

in the tumor while the doses in the healthy tissues remain within tolerances. 

Moreover, a better sparing of the brain than in conventional radiotherapy 

is obtained. 

347 oral 

DUAL-ENERGY CT IN MONTE CARLO TREATMENT PLANNING: A 

FEASIBILITY STUDY WITH A CANINE SUBJECT 

M. Bazalova 1 , J. F. Carrier 2 , L. Beaulieu 3 , F. Verhaegen 1 

1 

MCGILL UNIVERSITY HEALTH CENTER, Medical Physics, Montreal, 

Canada 

2 

HOPITAL NOTRE-DAME DU CHUM, Département de Radio-Oncologie, 

Montreal, Canada 

3 

CENTRE HOSPITALIER UNIV DE QUEBEC, Département de Radio- 

Oncologie, Quebec City, Canada 

Purpose: It has been previously shown that material segmentation is an important 

step in Monte Carlo dose calculations (MCDC), especially for kilovoltage 

photons. The aim of this study is to investigate the feasibility of dualenergy 

CT-based material extraction (DECT) for tissue segmentation and 

density assignment in MCDC for a phantom and a canine subject. 

Materials: CT images at two tube voltages (100kV and 140kV) of an RMI 

electron density CT phantom holding cylinders of different tissue-equivalent 

materials were acquired. The Z and ρ of the phantom were iteratively extracted 

by processing dual-energy CT images and the corresponding CT xray 

spectra. The CT x-ray spectra needed for an accurate extraction of Z and 

ρ were calculated by an analytical program. To test the feasibility of Z and 

ρ extraction for MC material segmentation, the RMI phantom with 17 inserts 

was used (Fig 1a). The Z and ρ were extracted for the 17 materials. ρ-maps 

were reconstructed using two approaches the commonly used single-energy 

CT approach (ρsingle) using a calibration curve and the dual-energy CT approach 

(ρdual) using DECT. A similar study was done on a canine subject. 

ρ-maps obtained by the two methods are compared and Z -maps are also 

extracted. 

Results: The Z and ρ of 17 tissue materials with Z varying from 5.74 to 14.14 

and ρ varying from 0.300 to 1.819 g/cm3 were extracted accurately, with a 

mean error of 3.2% and 1.8%, respectively. The ratios ρsingle/ρ and ρdual/ρ 

(Fig 1b and 1c) of the RMI phantom indicate that the ρ for soft bone tissue 

equivalent materials are overestimated using the single-energy approach by 

10% and 8%, respectively. The ρ of an adipose-equivalent cylinder is underestimated 

by 6%. The ρ assignment accuracy with DECT is within 2% 

with the exception of another low density adipose insert where the ρ is over-


estimated by 4%.In the canine study we found out that the DECT assigned 

ρdual-map (Fig 1e) is noisier than the ρsingle-map (Fig 1d). This was partially 

due to the noise in the original CT images and partially due to subject 

motion between the two scans. Disregarding the motion artifacts in the legs 

and in the intestines, the ratio of the two maps (Fig 1f) indicates a density 

overestimation of bone marrow with the single-energy approach, which is in 

agreement with the phantom study. The relatively noisy extracted Z -map is 

shown in Fig 1g where Z of bone marrow agrees with the published ICRU-44 

values. 

Conclusions: We have shown that material segmentation and density assignment 

using dual-energy CT images is possible for a phantom and a canine 

subject. The improvement in density assignment is significant especially 

for soft bone tissue equivalent materials, MCDC for the canine subject using 

DECT extracted mass densities and effective atomic numbers will be presented. 

Treatment Planning and Verification 

348 oral 

A COMPARISON OF TOMOTHERAPY AND CONVENTIONAL LINAC 

VERIFICATION IMAGING PRACTICES 

S. Sirois 1 , J. Gluszko 1 , M. Evans 2 , W. Parker 2 , C. Freeman 1 

1 

MCGILL UNIVERSITY HEALTH CENTRE, Radiation Oncology, Montreal, 

Canada 

2 

MCGILL UNIVERSITY HEALTH CENTRE, Medical Physics, Montreal, Canada 

Purpose: The use of intensity modulated radiation therapy (IMRT), mandates 

the use of reliable daily or weekly imaging techniques to minimize the risk of 

inter treatment mis-alignments. The purpose of this study was to investigate 

the change in image acquisition practices following the installation of a Hi-Art 

Tomotherapy unit and to compare the dose received by the patient during 

Tomotherapy MVCT to that of portal imaging on a conventional linear accelerator 

(linac). 

Materials: In order to compare the dose delivered to the patient from pretreatment 

imaging, ten consecutive patients who had undergone radiation 

treatment with IMRT on a Varian linear accelerator for head and neck tumors 

were compared to ten similar patients treated with IMRT on Tomotherapy. 

All patients received 70 Gy in 33 fractions. The total number of electronic 

portal images (linac) and MVCT scans (Tomotherapy) were recorded for each 

patient over their course of treatment. In addition the monitor units delivered 

during the imaging sequence was recorded for each patient. To determine 

the dose received by the patient, a calibrated ion chamber was placed in a 

tissue equivalent phantom with a geometry similar to that of the patient during 

treatment, and this set-up was then used to estimate the dose received by the 

patient during verification imaging. 

Results: Our imaging practice with the introduction of the Tomotherapy unit 

has been adapted to include the use of daily pre-treatment MVCT scanning 

for all patients and all fractions. This has been a change from our experience 

of using weekly pre-treatment portal imaging when using the conventional 

linac. The average number of electronic portal images taken per patient on 

the conventional linac over a full course of treatment was 19 at 6 MU per 

portal. Thus the average total dose delivered was approximately 1.2 Gy per 

patient. The average number of MVCT scans taken on Tomotherapy was 36, 

and the average total dose delivered was approximately 0.65 Gy per patient. 

It is apparent that the total dose delivered is a function of the number of 

verification images produced. The judicious choice of imaging techniques 

can reduce both the image acquisition time and dose delivered to the patient 

for both the conventional linac and the Tomotherapy unit. 

Conclusions: The average dose delivered with a daily MVCT (Tomotherapy) 

unit is lower than that from electronic portal images (linac) over a standard 

course of IMRT treatments. The introduction of a Tomotherapy unit with daily 

MVCT imaging lead us to question the dose delivered to the patient due to 

verification imaging. This study convinced us that daily MVCT imaging has 

definite clinical benefits without an increase in patient dose when compared 

to our experience with a conventional linac. 

349 oral 

DOSIMETRIC EVALUATION OF KV AND CONEBEAM IMAGE 

ACQUISITION USED FOR RADIOTHERAPY DAILY TREATMENT 

VERIFICATION 

I. Cardoso 1 , M. Pontes 1 , C. Souto 1 , A. Coutinho 1 , P. Carvoeiras 1 , S. 

Lopes 1 , M. Barreiros 1 , V. Santos 1 , M. Coelho 1 , M. Santos 1 , C. Borges 

1 , N. Teixeira 2 , P. Ferreira 2 , M. Ramalho 2 

1 CENTRO ONCOLÓGICO DR A NATÁLIA CHAVES, Lisboa, Portugal 

2 MEDICALCONSULT, Lisboa, Portugal 

Purpose: Radiotherapy treatments have become more complex as result of 

new treatment planning concepts, thus requiring new technological devices 

that allow a more sophisticated process control of the treatment workflow in a 

Radiotherapy Department. One of the main technologies that are presented 

as improvements used in treatment control and verification are based in kV 

image acquisition. Nevertheless this means more dose for the patient that 

should be taken into account when the total dose is analysed. The main goal 

of this work is to evaluate the dose that results from the use of KV and CBCT 

images for radiotherapy daily treatment verifications and how often they could 

be used. 

Materials: Images were obtained in fluoroscopic, radiographic and CBCT 

modes of an anthropomorphic phantom CIRS R○, to reproduce Head and 

Neck and pelvic regions, with the use on the On-Board Imager R○(OBI) 

Varian R○equipment. Acquisition parameters used were 125kV and 80mA, 

and measurements were obtained using 2 different cylindrical ionization 

chambers: 2 regular radiotherapy chambers with 0,125cc and 0,6cc, and using 

as reference the IAEA TRS398 and DIN 6809-5 protocols. 

Results: When the image acquisition is done using the fluoroscopic mode 

the average dose is near 0.035mGy and in the radiographic mode the value 

arises to 0.265mGy per incidence. With the use of CBCT, the average dose 

for each acquisition is around 4,4cGy, for pelvic region and 5cGy for Head 

and Neck localization. 

Conclusions: The obtained values of the 3 acquisition modes are substantial 

different when compared with the total treatment doses that are used in a 

conventional radiotherapy treatment. Observing the results and the possible 

number of uses during a total course of treatment with each type of image 

acquisition for treatment verification, is possible to say that the use of fluoroscopic 

and radiographic images doesn’t compromise or change significantly 

the total dose for each patient. However is not possible to have the same conclusions 

when we analyze the doses that are given to patient when is used the 

CBCT mode. Although this acquisition favours the knowledge of changes that 

occurs in soft tissues during the course of the treatment, the total dose given 

to a patient can be altered significantly, depending on the frequency that this 

image acquisition mode is used. So, for this case, it should be established, in 

each department and for each pathology, a protocol of use, in order to obtain 

the necessary information, without compromising the treatment goals. 

350 oral 

EFFICIENT AND ACCURATE IMRT VERIFICATION FOR ALL CURA- 

TIVE PATIENTS BY MEANS OF EPID DOSIMETRY 

R. Tielenburg 1 , A. Mans 1 , R. Vijlbrief 1 , M. Van de Burgt 1 , M. Baas 1 , L. 

McDermott 1 , M. Wendling 1 , M. van Herk 1 , B. Mijnheer 1 , J. Stroom 1 



Purpose: To provide an overview of the current clinical practice for individual 

IMRT plan verification in our institution by means of only EPID dosimetry, with 

high accuracy and a minimum of workload. 

Materials: Acquired EPID images are back-projected and converted to dose 

in a plane intersecting the isocenter and compared with the planned dose distribution 

by means of the γ index. All IMRT and all breast plans are verified 

in vivo, except for high dose, single fraction treatments or when the field size 

exceeds the detector size. In these cases, a pre-treatment check on a phantom 

is performed. With pre-treatment dosimetry, treatment planning system 

(TPS) dose calculation, plan transfer and plan deliverability are verified. With 

in vivo dosimetry, patient setup errors and anatomy changes can be detected 

as well. New plans are automatically detected when sent to the linac. The acquisition 

of open images (without patient; needed for back-projection model) 

is performed by dedicated radiographers and takes 10 min/plan. For every 

acquired portal image, the corresponding plan dose is automatically found. 

For normal fractionation schemes, an in vivo verification includes data from 

3 treatment fractions, and analysis must be completed before treatment of 

the 4th fraction. Currently, automatic decision rules are applied for prostate, 

rectum and head&neck verifications. The complete procedure is paperless. 

Results: From the total amount of 2500 plans per year (1900 patients), ~2320 

are verified in vivo and 180 pre-treatment. Yearly, we expect to do 100 pretreatment 

verifications extra because of discrepancies found in vivo. Averaged 

over all plans, the dose difference is 1.0% in the isocenter and the average 

of the mean γ (3%, 3mm) is 0.5. Due to a high degree of automation, the 

analysis of in vivo data and pre-treatment data takes 3 and 45 min (including 

preparation), respectively, and is mostly performed by two part time radiographers. 

The automatic decision rules have approved ~50% of prostate, rec-


tum and head&neck plans, however, currently all plans are finally approved 

by the responsible clinical physicist. Since 2005, 2-4 clinically relevant errors 

were detected yearly, such as patient anatomy changes and one serious plan 

transmission error. 

Conclusions: In our department, EPID dosimetry is used as the only, highly 

efficient and accurate tool for verification of all curative (99% IMRT) plans. 

With a minimum of workload, the radiotherapy chain is provided with a sophisticated 

safety net. 

351 oral 

WHAT ARE THE REQUIRED MARGINS TO COMPENSATE FOR 

CHANGES IN THE POSITION OF THE BLADDER TUMOUR IN 

ONLINE AND OFFLINE CORRECTED RADIOTHERAPY? 

M. Kamphuis 1 , D. van Rooijen 1 , A. Bel 1 

1 ACADEMIC MEDICAL CENTER, Radiation Oncology, Amsterdam, Nether- 

lands 

Purpose: First to evaluate the size of the margins used in offline protocols by 

calculating the actually given dose. Second to determine the size of the margins 

needed to compensate for bladder tumour motion in an online correction 

protocol . 

Materials: The investigation was carried out using the data of 8 patients with 

solitary bladder cancer, treated in the AMC. All patients received a dose of 40 

Gy in 20 daily fractions to the pelvis, with a daily 0.75 Gy concomitant boost 

on the bladder tumour plus margin. Patients underwent 7 to 9 follow-up CTscans. 

The GTV was delineated and the translations of the centre of gravity 

were registered relatively to the bone structures. Mean and SD of the translations 

were computed. Based on these data we calculated required margins 

using Van Herk’s margin recipe (2.5Σ + 0.7σ). For the X- Y- and Z-directions 

we needed a 3.9, 11.6 and 9.4 mm margin respectively. With the use of a 

pseudo-random number generator we created virtual translations for all 20 

fractions based on individual mean and SD. The impact of organ motion on 

the coverage of the GTV was studied by creating five margins of 0, 3, 6, 9, 

and 12 mm around the original GTV. The original treatment plan was adapted 

and recalculated for these five margins (99% of the GTV receives 95% of the 

prescribed dose). Created translations as well as adapted treatment plans 

were imported in APlan. This in-house developed program enables calculation 

of the actually delivered dose taking organ motion into account. For every 

patient, recalculation was performed per margin and per fraction. Calculation 

was performed with and without correction for tumour motion. All 20 fractions 

of the individual patients were added up. The DVH of the actually delivered 

dose was compared with the initial DVH without the inclusion of organ motion. 

Variations in bony anatomy were neglected because they are small in 

comparison to the motion of the tumour. 

Results: Without applying a margin, all patients received a far too low dosage 

of the GTV (up to 29%). However adequate coverage for all patients was 

obtained using the 12 mm margin. In seven patients tumour motion could 

easily be compensated by using a 9 mm margin. Online corrected treatment 

results in a complete dose coverage of the GTV without the use of margins. 

Conclusions: Calculation of actually given dose is a successful way of evaluating 

the size of applied margins. Without margins or correction serious 

underdosage occurs. Online correction is a save option for compensating 

bladder tumour motion. The size of margins correcting for organ motion in 

offline radiotherapy, as calculated with Van Herk’s margin recipe, is in agreement 

with the results of this study. 

352 oral 

PROPOSAL OF A NODAL AREA CONTOURING GUIDELINES FOR 

RECTAL CANCER TREATMENT: CLINICAL VALIDATION REPORT 

D. Pasini 1 , M. A. Gambacorta 1 , S. Manfrida 1 , M. C. Barba 1 , S. Arcangeli 

2 , R. D’Amico 1 , N. Dinapoli 1 , G. C. Mattiucci 1 , M. Balducci 1 , A. Mannocci 

3 , G. La Torre 3 , V. Valentini 1 

1 UNIVERSITÀ CATTOLICA DEL SACRO CUORE, Radiotherapy, Rome, Italy 

2 REGINA ELENA NATIONAL CANCER INSTITUTE, Radiotherapy, Rome, Italy 

3 UNIVERSITÀ CATTOLICA DEL SACRO CUORE, Hygiene-Epidemiology and 

Biostatistics , Rome, Italy 

Purpose: To assess if 2D treatment planning (TP) guidelines (Gunderson LL 

IJROBP. 11;1379-93;1985) for rectal cancer treatment are adequate to cover 

the volumes contoured on CT. 

Materials: CT of 30 pts were acquired. Nodal areas at risk were delineated 

on Eclipse-VARIAN-v.7.3.10-TPS: mesorectum (M), internal iliac (IIN), obturator 

nodes (ON) and external iliac nodes (EIN), PTV was obtained summing 

all these volumes + 1cm. According to CT, for each patient were created 2 

PTVs: PTV_T3 (M+ON+IIN) and PTV_T4 (M+ON+IIN+EIN). For each PTV 

were calculated 2 TP: a 2D based on bony landmarks and a 3D obtained 

adding 1cm between PTV and MLC. From each DVH were calculated the 

median dose and SD of 2D and 3D TP, compared (2D vs 3D) the percentage 

of volume covered by the dose, using non parametric Mann Whitney test, calculated, 

with the Wilcoxon test for two-related samples, the doses at which 

the lack of volume coverage started to decrease significantly. According to 

S 117 

the percentage of prescribed dose covering the 97% of the PTV, the treatment 

plans were defined: optimal when dose was > 97%, good when dose 

was between 97% and 90%, bad when dose was < 90%. The level of significance 

was set at p≤0.05. The statistical analysis was performed with SPSS 

12.00 per Windows. 

Results: In PTV_T3 the median volume (MV) receiving a dose > 97% was 

93.91% (SD 6.94) and 94.36% (SD 4.93), the MV receiving a dose > 105% 

was 1.29% (SD 1.92) and 1.31% (SD 1.66), in 2D and 3D plan respectively. In 

PTV_T4 the MV receiving a dose > 97% was 89.31% (SD 7.18) and 92.59% 

(SD 5.4), the MV receiving a dose > 105% was .75% (SD 1.37) and 1.82% 

(SD 2.02), in 2D and 3D plan respectively. The difference between 2D and 3D 

TP, in cT3 pts, was significant in these dose intervals: 29%-95% in PTV_T3, 

35.5%-94% in M, 37%-97% in ON and 69%-95% in IIN; the difference between 

2D and 3D TP, in cT4 patients, were significantly different in these interval 

of doses 7%-97% in PTV_T4, 81%-96%, in M, 97%-99% in ON, 89%- 

93.5% in IIN, 10.5%-106% in EIN. In cT3 pts the volume coverage started 

to decrease significantly at these dose levels: 29.5-30% (2D) and 88.5-89% 

(3D) in PTV_T3, 84-84.5% (2D) and 93-93.5% (3D) in M, 91-91.5% (2D) and 

95.5-96% (3D) in ON, 93-93.5% (2D) and 95-95.5% (3D) in IIN; in cT4 pts the 

volume coverage started to decrease significantly at these dose levels: 6.5- 

7% (2D) and 87-87.5% (3D) in PTV_T4, 88.5-89% (2D) and 93-93.5% (3D) 

in M, 98-98.5% (2D) and 96.5-97% (3D) in ON, 91-91.5% (2D) and 93.5-94% 

(3D) in IIN, 11-11.5% (2D) and 94-94.5% (3D) in EIN. Comparing 2D vs 3D 

plans, the coverage of PTV_T3 was optimal in 15/30(50%) and 14/30(46.7%), 

good in 10/30 (33.3%) and 16/30(53.3%) and bad in 5/30 (16.7%) and 0; the 

coverage of PTV_T4 was optimal in 5/30(16.7%) and 4/30(13.4%), good in 

0% and 25/30(83.3%) and bad in 25/30(83.3%) and 1/30(3.3%). 

Conclusions: 2D technique seems insufficient to cover the volumes contoured 

on CT, 3D treatment plan is recommended in all stages of rectal cancer. 

Social structure, risk management and other aspects 

353 oral 

A POPULATION - BASED STUDY OF THE FRACTIONATION OF 

POST - LUMPECTOMY BREAST RADIOTHERAPY IN ONTARIO 

A. Ashworth 1 , W. Kong 1 , T. Whelan 2 , W. MacKillop 1 

1 QUEEN’S CANCER RESEARCH INSTITUTE, QUEEN’S UNIVERSITY, Cancer 

Care Epidemiology, Kingston, Canada 

2 JURAVINSKI CANCER CENTRE, MCMASTER UNIVERSITY, Department of 

Clinical Epidemiology Biostatistics, Hamilton, Canada 

Purpose: 

1. To describe the fractionation of post-lumpectomy radiotherapy (PL-RT) 

used in Ontario between 1984-2004. 

2. To test the hypothesis that the results of the Ontario Clinical Oncology 

Group (OCOG) Trial 1 , which showed the equivalence of 16 and 25fraction 

RT schedules, resulted in more frequent use of the 16-fraction 

schedule. 

Materials: Electronic RT records from all provincial RT centers in Ontario and 

surgical treatment records from the Canadian Institute for Health Information 

were linked to the Ontario Cancer Registry to identify all breast cancer patients 

treated with PL-RT in Ontario between 1984-2004. Observed patterns 

of fractionation were correlated with the dates of publication of landmark clinical 

trials. 

Results: Over the 20-year study period, 33,481 patients received PL-RT in 

Ontario. The most commonly prescribed number of fractions/course were 16 

and 25 fractions. A smaller proportion of courses were administered in 20, 

21 or 30 fractions, representing courses of 16 or 25 fractions to the whole 

breast with 4-5 boost fractions. Over the entire study period, fractionation 

varied widely among the nine Ontario cancer centers; the mean number of 

fractions/course was 21, ranging from 18-24. The 16-fraction RT schedule 

was the most commonly used schedule in Ontario in the early 1980’s. After 

1985, there is a shift towards use of the 25-fraction schedule coinciding with 

publication of the NSAPB-06 study. By 1997, 73% of all PL-RT courses in 

Ontario used the 25-fraction schedule. There was a dramatic shift in fractionation 

practices between 1997 and 2002, prior to publication of the OCOG 

trial, when the percentage of courses using the 16-fraction schedule nearly 

doubled, peaking in 2002 at 72%. Use of this schedule subsequently declined 

to 63%. Inter-centre variations in practice patterns persisted after publication 

of the OCOG trial. 

Conclusions: Contrary to our hypothesis, a shift in practice patterns favouring 

the shorter 16-fraction RT schedule occurred prior to publication of the 

OCOG trial. 1 Whelan T, MacKenzie R, Julian J, Levine M, Shelley W, Grimard 

L, et al. Randomized trial of breast irradiation schedules after lumpectomy 

for women with lymph node-negative breast cancer. Journal of the National 

Cancer Institute 2002;94:1143.


354 oral 

VARIATION IN DELINEATION OF THE GTV, CTV AND PTV BETWEEN 

THE TRAINING INSTITUTES FOR RADIATION ONCOLOGISTS IN 

THE NETHERLANDS 

L. Uitterhoeve 1 , J. Duppen 2 , Y. v.d.Linden 3 , R. Haas 2 , M. Olofsen-v.Acht 

4 , C. Terhaard 5 , R. Nout 6 , E. Zwijnenburg 4 , E. Wiegman 7 , C. Hurkmans 

8 , I. K. Kolkman-Deurloo 4 , C. Marijnen 2 

1 

ACADEMIC MEDICAL CENTER, Department of Radiotherapy, Amsterdam, 

Netherlands 

2 

NETHERLAND CANCER INSTITUTE, Department of Radiotherapy, Amsterdam, 

Netherlands 

3 

RADIOTHERAPEUTISCH INSTITUUT FRIESLAND, Leeuwarden, Netherlands 

4 

ERASMUS MEDICAL CENTER, Department of Radiation Oncology, 


5 

UNIVERSITY MEDICAL CENTER UTRECHT, Department of Radiation 

Oncology, Utrecht, Netherlands 

6 

LEIDEN UNIVERSITY MEDICAL CENTER, Radiation Oncology, Leiden, 

Netherlands 

7 

UNIVERSITY MEDICAL CENTER GRONINGEN, Department of Radiation 

Oncology, Groningen, Netherlands 

8 

CATHARINA ZIEKENHUIS, Department of Radiotherapy, Eindhoven, 

Netherlands 

Purpose: The education of the 75 residents in training for Radiation Oncologist 

in the Netherlands is partly organized partly on a national basis, partly 

on an institutional basis. The nationally organized part consists of 2 training 

days per year, 10 in total for the entire training period of 5 years. Each 

day focuses on a subject of clinical oncology. The following subjects are discussed: 

breast cancer, lung cancer, neurological tumours, gynaecological tumours, 

urological tumours, head and neck cancer, gastro-intestinal tumours, 

haemato-oncology, soft tissue sarcomas, skin cancer, and palliation. Before 

each of these days 20 key articles about the subject are studied. The residents 

have to make a patient case including delineation of the GTV (if appropriate), 

the CTV and the PTV on an institutional base. The answers and 

delineations are analyzed and discussed during the meeting in the presence 

of several experts in the field.. Apart from these subjects a course of radiobiology, 

of basic radiation physics, and a course of imaging techniques and 

treatment planning is mandatory. A written examination test is obligatory for 

all residents on each training course or day. 

Materials: Four case histories with electronic data of clinical questions and 

GTV-, and CTV- contours are available for analysis (breast, lung, vulvar and 

rectal cancer). 

Results: Data are present from 9 university training institutes and from 5 

affiliated training hospitals. There is not much diversity in the answers on the 

clinical questions. The delineation of the GTV and CTV varies widely from 

one institution to another. However, the chosen margin between the CTV and 

the PTV is very uniform. If articles with delineation guidelines were enclosed 

in the mandatory list of articles to be studied, less variation was seen in GTV 

and CTV contours. Case and delineation analysis are a highly appreciated 

part of the national training program and led to a higher level of agreement 

between residents. 

Conclusions: On a national basis insight in the variation between training 

institutes concerning GTV and CTV delineation should be an obligatory part 

of the training of residents in Radiation Oncology. Guidelines in the literature 

about delineation of the GTV and CTV are needed.. The educational system 

in the Netherlands guaranties a basic quality of oncological knowledge and 

skills of the residents in Radiation Oncology at the end of their training period. 

This approach may be very well applicable to a European based educational 

system. 

355 oral 

QUALITY ASSURANCE TEAMS FOR RADIATION ONCOLOGY 

(QUATRO): COMPREHENSIVE AUDITS IN RADIOTHERAPY IN 

CENTRAL AND EASTERN EUROPE 

J. Izewska 1 , E. Salminen 1 , E. Zubizarreta 1 

1 IAEA, Vienna, Austria 

Purpose: The objective of a comprehensive clinical audit is to review and 

evaluate the quality of all components of the practice of radiotherapy with a 

view for quality improvement. The comprehensive audit addresses the various 

aspects of radiotherapy practices, such as equipment, staffing, infrastructure 

and the operation of services. 

Materials: A guidance document "Comprehensive Audits of Radiotherapy 

Practices: A Tool for Quality Improvement" has been published by the IAEA. 

It provides a general audit methodology that can be applied in a range of economic 

settings. This activity is given a name of "Quality Assurance Team for 

Radiation Oncology (QUATRO)". QUATRO procedures have been endorsed 

by ESTRO, EFOMP and IOMP. A multidisciplinary team comprising a radiation 

oncologist, a medical physicist and a radiotherapy technologist carries 

out the audit. A major part of the audit is patient-oriented and the audit procedures 

follow the path of a patient from the diagnosis and decision to treat, 

through treatment prescription, planning, treatment preparation and delivery, 

and finally through the follow-up process. 

Results: Several workshops on the QUATRO methodology were run by the 

IAEA in 2005-2006 to train the audit teams and hospital staff prior to fielding 

QUATRO missions. Since 2005, the IAEA has organized over 25 QUATRO 

audits based on the voluntary requests by its Member States in Africa, Asia, 

Europe and Latin America. Two ’lessons learned’ meetings were convened 

in 2007 with both auditors and auditees of Europe and Asia to collect their 

feedback on the process of QUATRO, exchange experiences and outline future 

activities. The conclusion of missions conducted in Central and Eastern 

Europe suggested that three of the 15 audited centres operate to international 

standards and several centres represent good professional and technical 

level with well trained, hard working and dedicated staff. However, equipment 

and staff shortages constitute a general problem; in particular training of 

RTTs requires to be improved. Also, insufficient funding of radiotherapy operations 

has been noted with poor sustainability of resources in some countries. 

Conclusions: To summarize, QUATRO provides a useful tool for improvement 

of radiotherapy practices. The IAEA is the first international organization 

who prepared the methodology, trained experts and started the implementation 

of the comprehensive audit in radiotherapy worldwide. In the future the 

QUATRO methodology will be transferred to the national level. Acknowledgement 

Numerous experts who conducted QUATRO missions in Europe are 

acknowledged. 

356 oral 

STAFFING AND EQUIPMENT OF RT CENTRES; COMPARING 

THE PROPOSED EORTC GUIDELINES TO ESTRO AND DUTCH 

GUIDELINES 

C. Hurkmans 1 , T. Budiharto 2 , E. Musat 2 , P. Poortmans 3 , A. Monti 4 , R. 

Bar-Deroma 5 , Z. Bernstein 5 , G. van Tienhoven 6 , L. Collette 2 , B. Davis 7 , 

E. Aird 8 , B. Slotman 9 , P. Vos 3 

1 

CATHARINA HOSPITAL, Radiotherapy, Eindhoven, Netherlands 

2 

EORTC, Head Quarters, Brussels, Belgium 

3 

DR. BERNARD VERBEETEN INSTITUUT, Radiotherapy, Tilburg, Netherlands 

4 

ST ANNA HOSPITAL, Medical Physics, Como, Italy 

5 

RAMBAM MEDICAL CENTRE, Radiation Oncology, Haifa, Israel 

6 

ACADEMIC MEDICAL CENTRE, Radiotherapy, Amsterdam, Netherlands 

7 

UNIVERSITAETSSPITALKLINIK RADIO-ONKOLOGIE, Radiotherapy, Zurich, 

Switzerland 

8 

MOUNT VERNON HOSPITAL, Medical Physics, Northwood Middlesex, 


9 

FREE UNIVERSITY HOSPITAL, Radiotherapy, Amsterdam, Netherlands 

Purpose: First, to compare the updated recommendations on staffing and 

equipment for EORTC ROG centres to the ESTRO 2005 and the Dutch 2007 

guidelines. Second, to suggest a common framework for future guidelines. 

Materials: The guidelines and associated underlying data from the three surveys 

were analysed. For the Dutch guidelines, the guidelines were recalculated 

to number of patients per Full-Time-Equivalent (or per equipment unit). 

Results: Both EORTC and ESTRO have based their workload definitions on 

the number of patients that receive radiotherapy. The Dutch NVRO guidelines 

refined the workload calculations by introducing 4 radiotherapy complexity 

classes for teletherapy and 5 classes of brachytherapy. Using this 

latter refinement, a more than merely patient numbers related workload increase 

could be foreseen, which stimulated timely planning of investments. 

The more recent EORTC and Dutch guidelines are similar to the slightly older 

ESTRO guidelines (see table). However, an increase of throughput for CT 

scanners/simulators is foreseen, reflecting the increased replacement of conventional 

simulators by time efficient CT scanners. The ESTRO guidelines 

are based on a survey of national guidelines, whereas the EORTC and Dutch 

guidelines are based on actual infrastructure information. Although all three


surveys collected data on technologist staffing and treatment planning equipment, 

no guidelines were formulated for these important topics. However, 

minimum requirements have been set in the EORTC and Dutch (in brackets) 

guidelines as follows: MV units: 2 (4); radiation oncologists: 3 (8); and clinical 

physicists: 2 (3). 

Conclusions: The various guidelines are reasonably similar but figures for 

technologists and infrastructure other than MV units are missing. The suggested 

set of minimum facility requirements for a department varies much 

more, reflecting the huge variance throughout Europe. Overall, there exists a 

need for more comprehensive guidelines that closely follow trends in technology 

and workload. 

357 oral 

TECHNICAL ERRORS AND INCIDENTS IN RADIOTHERAPY PRO- 

CESS: COMPARISON OF 5-10 YEAR FOLLOW-UP IN TWO FINNISH 

HOSPITALS 

P. Arponen 1 , S. Hyödynmaa 2 , A. Karhu-Hämäläinen 1 , M. Pitkänen 2 , M. 

Tenhunen 1 

1 

HELSINKI UNIVERSITY CENTRAL HOSPITAL, Radiotherapy, Helsinki, 

Finland 

2 

TAMPERE UNIVERSITY HOSPITAL, Radiotherapy, Tampere, Finland 

Purpose: Due to the rapid development of the radiotherapy techniques, the 

accuracy of radiotherapy has improved. However, the possibility of different 

errors and incidents has increased. In this study we analyzed the type and 

number of errors and incidents taken place in radiotherapy (RT) process during 

5-10 years. 

Materials: The study consists of 37800 treated RT patients from two hospitals:Helsinki 

University Central Hospital (HUCH) and Tampere University 

Hospital (TAUH) in Finland. The two hospitals have been collecting data on 

occurred errors in RT process since 2002 and 1997, respectively. All deviations 

were recorded on a dedicated sheet by anyone observing it. Each 

incident was checked and immediate corrective actions taken if needed. Basically 

there were two types of deviations: A) those leading to a dose deviation 

in treatment and B) those detected before treatment, not resulting in dose 

error. All incidents in group A were classified into 3 categories: 1) 0-5%, 

2) 5-10% and 3) >10% error in dose to target (according Yeung et al. from 

North-Eastern Ontario Regional Cancer Centre, Radiother&Oncol 2005). All 

reported events were presented to the whole staff with the purpose of learning 

from errors on a regular basis. 

Results: During years 1997-2006 about 60000 (HUCH) and 30000 (TAUH) 

RT fractions/year were given, on average 17.3 fractions/patient. The total 

number of treated fields during that time has nearly doubled. Reports on 

various deviations, including documentation were given on average in 4,1% 

of cases. Table 1 shows the percentage of various errors in each category 

related to the number of patients. Typical major errors were associated with 

wrong patient, monitor units, shielding, field size or location. We noticed 

a decrease in errors of >10% and diminishing trend in events 10% errors and reduced the smaller ones. Results are 

in good agreement with those reported by Yeung. Errors are more often discovered 

before they take place in treatment. Open discussion and feedback 

contributes to learning from OUR errors. 

358 oral 

S 119 

RISK ANALYSIS METHODS: THEIR IMPORTANCE FOR THE 

SAFETY ASSESSMENT OF RADIOTHERAPY 

P. Ortiz Lopez 1 , M. L. Ramirez 2 , C. Dumenigo 3 , J. D. McDonnell 4 , J. J. 

Vilaragut 5 , S. Papadopulos 6 , P. P. Pereira 7 , M. Gonçalves 8 , J. Morales 

9 10 11 12 13 

, R. Ferro , R. López Morones , J. M. Delgado , F. Somoano , C. 

Álvarez 2 , A. Guillén 14 , M. Rodriguez 15 

1 

INTERNATIONAL ATOMIC ENERGY AGENCY, Safety and security coordination 

section, Vienna, Austria 

2 

CONSEJO DE SEGURIDAD NUCLEAR, Instalaciones Radiactivas Médicas, 

Madrid, Spain 

3 

CENTRO NACIONAL DE SEGURIDAD NUCLEAR, Licenciamiento , La 

Habana, Cuba 

4 

UNIVERSIDAD NACIONAL DE ROSARIO, Radiofisica, Rosario, Argentina 

5 

CENTRO NACIONAL DE SEGURIDAD NUCLEAR, Anáisis Probabilista de 

Seguridad, La Habana, Cuba 

6 

AUTORIDAD REGULATORIA NUCLEAR, Inspección, Buenos Aires, Argentina 

7 

INSTITUTO NACIONAL DE CANCER, Radioterapia, Rio de Janeiro - RJ, 

Brazil 

8 

INSTITUTO DE RADIOPROTEÇÃO E DOSIMETRIA, COMISSAO NACIONAL DE 

ENERGIA NUCLEAR (C, Inspección, Rio de Janeiro, Brazil 

9 

INSTITUTO NACIONAL DE ONCOLOGÍA Y RADIOBIOLOGÍA, Física de 

Radioterapia, La Habana, Cuba 

10 

CENTRO NACIONAL DE SEGURIDAD NUCLEAR, Análisis Probabilista de 

Seguridad, La Habana, Cuba 

11 

COMISIÓN NACIONAL DE SEGURIDAD NUCLEAR Y SALVAGUARDIAS, 

Análisis Probabilista de Seguridad, Mexico, City, Mexico 

12 

INSTITUTO MADRILEÑO DE ONCOLOGIA, Física de Radioterapia, Madrid, 

Spain 

13 

ELEKTA MEDICAL S.A., Servicio Técnico, Madrid, Spain 

14 

CENTRO NACIONAL DE SEGURIDAD NUCLEAR, Dirección, La Habana, 

Cuba 

15 

CONSEJO DE SEGURIDAD NUCLEAR, Subdirección General de Seguridad 

Operacional, Madrid, Spain 

Purpose: Radiation safety has largely been based on compliance with regulatory 

requirements, codes of practice and international standards, which 

can be considered a "prescriptive method". Lessons learned from accident 

analysis have been published, and incorporated into safety assessments, in 

order to check whether a facility is safe enough to avoid accidents, similar to 

the reported ones. This approach can be also called "reactive method". The 

limitation of both approaches is that of being confined to reported experience, 

i.e., they do not primarily address the question of "what else can go wrong", 

and for this reason, latent risks from other potential events, which were never 

published or never happened, remain unaddressed. Moreover, the two approaches 

focus on events with major consequences and low probability but 

may not pay enough attention to others with higher probability and lower, but 

still significant, consequences. More "proactive approaches" are, therefore, 

needed, to systematically assess risk in radiation facilities, by identifying all 

potential equipment faults and human error, which can lead to predefined unwanted 

consequences and by evaluating their importance as a combination

S 120 AWARD LECTURE TUESDAY, SEPTEMBER 16, 2008 

of likelihood of occurrence and severity of the consequences. This article 

is aimed at describing the work done by a group involving radiation oncologists, 

physicists, safety specialists, regulators, and manufacturers on applying 

"proactive approaches" to radiotherapy. The work is done under a project of 

the Ibero American Forum of Nuclear and Radiation Safety Regulatory Organizations 

(the FORO). 

Materials: Two methods were applied in this project: probabilistic safety assessment 

(PSA) was used for external beam treatments with linear electron 

accelerators; and the risk-matrix approach was applied for cobalt 60 external 

beam therapy and brachytherapy and is being applied to treatment with 

accelerators. 

Results: In this work event sequences were identified, their likelihood of occurrence, 

the consequences, the efficiency of interlocks and control checks 

were evaluated and the global importance in terms of overall risk was estimated, 

in order to facilitate decision making and implementation of preventive 

measures. 

Conclusions: A comparison is presented of indications and limitations of 

each method, in terms of practical application and resources required. Finally, 

ways are described to extend this experience to other countries in form of pilot 

exercises. 

Award lecture 

Breur lecture 

359 speaker 

ADAPTIVE RADIATION ONCOLOGY BASED ON MOLECULAR AND 

FUNCTIONAL IMAGING 

D. R. Olsen 1 

1 DNR - NORWEGIAN RADIUM HOSPITAL, Institute for Cancer Research, 

Oslo, Norway 

Progress in molecular and functional imaging opens new possibilities for the 

optimization of radiation therapy for the individual cancer patient. Conventional 

anatomical and morphological imaging has for many years been critical 

for accurate target volume delineation. More recently, image guided radiation 

therapy has successfully led to high precision delivery of fractionated radiation 

therapy. The use of medical imaging in radiation oncology is currently 

experiencing a shift of paradigm as molecular and functional imaging is being 

introduced into modern treatment planning and in early response monitoring 

and prediction. Information about biological and physiological processes of 

relevance for the response to treatment is provided, non-invasively, by these 

techniques. As such they are expected to leverage the further development 

towards individualized radiation oncology. Not only will molecular and functional 

imaging be of value in deciding where the radiation should be delivered 

but also with respect to how. Recent PET research has led to the development 

of a number of tracers of interest for radiation oncology, enabling 

visualization of cellular metabolism and proliferation, apoptosis, angiogenesis, 

hypoxia as well as receptor status of tumours. In contrast to PET, MR 

imaging provide mainly indirect information about biological characteristics 

of the tumour. Diffusion MR imaging has been shown to provide information 

about cell death. Analysis of dynamic contrast enhanced MR imaging - 

using tumour kinetic models - provide information about perfusion and may 

thus be of relevance to e.g. tumour hypoxia. Measurement of tumour bioenergetic 

status, by 31 P-MR spectroscopy, has demonstrated to provide information 

about tumour hypoxia as well as treatment response. In prostate 

cancer maps of choline, creatine vs. citrate ratios, measured by 1 H-MR spectroscopy, 

has already been utilized in guiding boost treatment. Molecular and 

functional imaging represents potentially vast amount of information relevant 

for the response to radiation therapy, and will most likely have major impacts 

on radiation oncology planning in the coming years. However, a pre-requisite 

for the utilization and incorporation of this information into 4D (i.e. temporal 

as well as spatial) radiation oncology planning is: 1) further validation of the 

information provided by the imaging modalities, 2) investigation of temporal 

as well as spatial variation within individual tumours, 3) development of probabilistic 

rather than deterministic strategies for translating the information into 

treatment plan requirements, and 4) development of strategies that account 

for multi-modality imaging that provide not necessarily unique and unambiguous 

information. If we successfully address these questions molecular and 

functional imaging will represent the next frontier in individualized radiation 

oncology.



Highlights of the proffered papers 

360 oral 

ACCELERATED RADIOTHERAPY AND/OR CONCOMITANT 

CHEMOTHERAPY IN LOCALLY ADVANCED HEAD AND NECK SCC: 

RESULTS OF A GORTEC RANDOMIZED TRIAL. (ON BEHALF OF 

THE GORTEC) 

J. Bourhis 1 , C. Sire 2 , M. Lapeyre 3 , V. Grégoire 4 , P. Maingon 5 , G. Calais 

6 7 8 9 10 11 

, L. Martin , M. Alfonsi , P. Deprez , T. Pignon , E. Bardet , A. 

Lusinchi 9 , A. Aupérin 9 

1 

INSTITUT GUSTAVE ROUSSY, Villejuif, France 

2 

CHBS LORIENT, Lorient, France 

3 

CENTRE JEAN PERRIN, Clermont Ferrand, France 

4 

UCL CLINIQUES UNIV. ST.LUC, Brussels, Belgium 

5 

CENTRE GEORGES-FRANÇOIS LECLERC, Dijon, France 

6 

HÔPITAL BRETONNEAU, Tours, France 

7 

CENTRE GUILLAUME LE CONQUÉRANT, Le Havre, France 

8 

HÔPITAL JOSEPH IMBERT, Arles, France 

9 

INSTITUT GUSTAVE ROUSSY, Biostatistics and Applied Mathematics, 

Villejuif, France 

10 

UNIVERSITY HOSPITAL LA TIMONE, Marseille, France 

11 

CENTRE RENÉ GAUDUCHEAU, Saint-Herblain, France 

Purpose: Previous meta-analyses and GORTEC randomised trials have 

shown that either accelerated radiotherapy (RT) or concomitant RTchemotherapy 

(CT), were both superior to conventional RT in terms of tumor 

control and survival, in patients with locally advanced head and neck squamous 

cell carcinomas (HNSCC). Based on these results, a randomised trial 

was designed to evaluate the value of combining both accelerated RT (Acc- 

RT) and concomitant CT in this type of patients. 

Materials: The hypothesis tested was that the combination of Acc-RT + CT 

would lead to a 15% improvement in progression free survival (PFS) at 3 

years, as compared to either very Acc-RT alone or to conventional RT + CT. 

To answer this question 840 patients with locally advanced HNSCC were randomised 

between 2000 an 2007 in 22 GORTEC centers to receive 70 Gy in 

7 weeks + 3 cycles of concomitant carboplatin and 5FU (Calais et al JNCI 

1999) (arm A) or 70 Gy in 6 weeks (Acc concomitant boost) + 2 cycles of 

carboplatin-5FU (Arm B) or very Acc-RT, 64.8 Gy in 3.5 weeks without CT 

(1.8 Gy BID) (Arm C). 

Results: There was no imbalance between the 3 arms regarding age (mean 

55) stage (91% T3-T4 ; 79% N1-N3), gender (87% males), tumor site (66% 

oropharynx) and all the other patient/tumor related factors. The compliance 

to chemotherapy was relatively good (3 cycles as planned in 76% of cases 

in arm A and 2 cycles as planned in 93% of cases in arm B). The RT dose 

and overall time were as per protocol with no major deviation in 91%, 91% 

and 88% in arm A, B and C, respectively.Acute mucosal toxicity was more 

severe in the very Acc-RT arm, as compared to the 2 CT arms. However 

when considering all types of toxicities, there was no significant difference in 

acute toxicity between the 3 arms and only slight differences were observed. 

Indeed, at least one grade 3-4 toxicity was seen in 83% of the patients in the 

conventional RT + CT arm, compared to 89% in the 2 other arms. With a median 

follow-up of 3.5 years, 449 patients died and 511 events were observed 

(relapse, progression, second primary or death). There was no difference 

between the 3 arms regarding loco-regional failure and survival. PFS at 3 

years was not different between the 2 chemotherapy arms, however PFS was 

significantly better in the conventional RT + CT arm as compared to the very 

Acc-RT arm (p=0.03). The data were not mature enough to evaluate late 

toxicity. 

Conclusions: the hypothesis that combining Acc-RT + CT would improve 

PFS, as compared to conventional RT + CT or to very Acc-RT was not confirmed. 

Conventional RT + CT provided the best ratio efficacy / tolerance, as 

compared to the 2 other arms. 

361 oral 

TWO-YEAR RESULTS FROM A SWEDISH STUDY ON CONVEN- 

TIONAL VERSUS ACCELERATED RADIOTHERAPY IN HEAD AND 

NECK SQUAMOUS CELL CARCINOMA (ARTSCAN) 

B. Zackrisson 1 , E. Kjellén 1 , T. Björk-Eriksson 2 , S. Friesland 3 , J. 

Reizenstein 4 , M. Lagerlund 5 , L. Ekberg 6 , B. Lödén 7 , J. Ahlgren 8 , C. 

Lindholm 9 , E. Brun 10 , C. Mercke 3 , J. O. Fernberg 3 , K. A. Johansson 11 , 

S 121 

J. Rzepecki 12 , H. Sjödin 5 , P. Nilsson 1 

1 

UMEÅ UNIVERSITY HOSPITAL, Oncology, Umeå, Sweden 

2 


3 

KAROLINSKA UNIVERSITY HOSPITAL AT SOLNA, Oncology, Stockholm, 

Sweden 

4 

ÖREBRO UNIVERSITY HOSPITAL, Oncology, Örebro, Sweden 

5 

KAROLINSKA UNIVERSITY HOSPITAL AT HUDDINGE, Oncology, Stockholm, 

Sweden 

6 

MALMÖ UNIVERSITY HOSPITAL, Oncology, Malmö, Sweden 

7 

KARLSTAD CENTRAL HOSPITAL, Oncology, Karlstad, Sweden 

8 

GÄVLE HOSPITAL, Oncology, Gävle, Sweden 

9 

RYHOV COUNTY HOSPITAL, Oncology, Jönköping, Sweden 

10 

LUND UNIVERSITY HOSPITAL, Oncology, Lund, Sweden 

11 


12 

LINKÖPING UNIVERSITY HOSPITAL, Oncology, Linköping, Sweden 

Purpose: Some studies on accelerated fractionation (AF) have shown increased 

efficacy in the treatment of head and neck cancers while others have 

been non-conclusive. Many of these studies have included too few patients 

to draw firm conclusions about outcome. In 1998 a national Swedish group 

decided to perform a randomised controlled clinical study of AF. 

Materials: Patients with verified squamous cell carcinoma of the oral cavity, 

oropharynx, larynx (except glottic T1-T2, N0) and hypopharynx were included. 

Patients with prior chemotherapy or prior surgery, other than diagnostic, 

were excluded. Patients were randomised to either conventional fractionation 

(2 Gy/day, 5 days/week in 49 days, total dose 68 Gy) or to accelerated 

(1.1 + 2.0 Gy/day, 5 days/week in 35 days, total dose 68 Gy). PTVa contained 

GTV and volumes for prophylactic treatment to 46 Gy. PTVb(oost), comprising 

GTV with a margin, thus received an additional 22 Gy. In the accelerated 

(concomitant boost) schedule the PTVb was treated with 1.1 Gy in the morning 

session in 20 fractions while PTVa concomitantly received 2.0 Gy in the 

afternoon session in 23 fractions. Hence, three treatment days contained only 

one fraction. In the conventional treatment arm PTVa was treated with 2.0 Gy 

during the first 23 fractions while PTVb received the same dose/fraction during 

the following eleven fractions. An extensive QA protocol, e.g. consisting 

of central monitoring of the treatment process, was followed throughout the 

study. The primary end point was local tumour control. Other end points were 

survival, acute and late morbidity and quality of life after five years. 

Results: The study was closed in June 2006 when 750 patients had been 

randomised. The median age was 62 years (range 26-91). 83% of the patients 

had stage III-IV disease. 48% had oropharyngeal, 21% laryngeal, 17% 

hypopharyngeal and 14% oral cancers. The first per protocol analysis with 

>90% of the patients having a follow-up time >2 years is ongoing. Two-year 

data regarding loco-regional control, overall survival and morbidity will be presented. 

Conclusions: The study has served as a tool for achieving a national consensus 

on treatment of these diseases. The results will be used for establishing 

standards for treatment in Sweden that will serve as baseline for future 

studies. 

362 oral 

QUANTIFYING THE ROBUSTNESS OF IMRT TREATMENT PLANS 

FROM A STATISTICAL OPTIMIZATION MODEL TO ACCOUNT FOR 

ORGAN DEFORMATION 

B. Sobotta 1 , M. Söhn 1 , M. Alber 1 

1 RADIOONCOLOGICAL CLINIC, UNIVERSITY OF TÜBINGEN, Section for 

biomedical physics, Tübingen, Germany 

Purpose: Organ movement is still the biggest challenge in prostate treatment 

despite advances in online imaging. The residual uncertainty about the 

patient geometry can be captured by a limited number of CTs, which provide 

only incomplete information about the organ motion. To alleviate this problem, 

a statistical model of motion is created using Principle Component Analysis 

(PCA). The dose is optimized with this deformable patient model, whilst the 

uncertainty of the dose quality metrics is assessed by a machine learning 

algorithm. 

Materials: Starting from multiple CT images, a PCA model of the patient is 

created. The EUD is evaluated for a multitude of geometry instances sampled 

from the PCA model. The PCA model serves as a generator of synthetic 

patient geometries. In contrast to the Coverage Probability approach, a statistical 

distribution of each separate dose metric is obtained incorporating the 

correlated movement of all volumes of interest (VOI).The subsequent calculation 

of the mean and variance of the EUD allows for a viable estimate of the 

expected treatment outcome along with the residual uncertainty. In addition, 

joint distributions of outcome metrics for different VOIs can be generated.The 

algorithm was implemented into the clinical IMRT-planning software Hyperion, 

which utilizes EUD-based biological optimization. The calculation time 

for a prostate plan on an up-to-date multicore workstation is in the order of an 

hour. 

Results: The dose distribution is optimized given the patient specific mobility 

of the organs. Since an estimate of the uncertainty of the delivered EUD is 

given, the method provides insight about the potential need of further setup 

correction or online imaging. Hence, a robust plan with respect to geometrical

S 122 

PROFFERED PAPER 

deviations of the PTV and the OARs is obtained. Due to the independent evaluation 

of each geometry instance, the correlation of dose metrics between 

individual organs is revealed. This substantial information gain facilitates the 

inevitable tradeoff between OAR sparing and tumour control. 

Conclusions: Based on a few CTs, the proposed method is able to create 

robust treatment plans while remaining clinically practical. This is also applicable 

to compensate for the residual error of online-setup protocols. By 

quantifying the uncertainty of the treatment outcome, it provides a measure 

for the robustness of the plan. Since the only information required is a probability 

density function along with samples of the support, other inputs than 

PCA are conceivable. 

TUESDAY, 

SEPTEMBER 16, 2008

WEDNESDAY, SEPTEMBER 17, 2008 SYMPOSIUM 

Wednesday, September 17, 2008 


Biologic basis for re-irradiation and current clinical 

concepts 

369 speaker 

REIRRADIATION: BIOLOGICAL BASIS, TECHNIQUES AND RE- 

SULTS 

C. Nieder 1 

1 NORDLANDSSYKEHUSET HF, Medical Department - Oncology Radiation 

Oncology, Bodoe, Norway 

To summarize experimental data related to normal tissue tolerance and recovery 

processes and to provide clinical data obtained with different reirradiation 

techniques and regimens in different disease entities. The literature 

on both experimental and clinical reirradiation studies is being reviewed. A 

considerable number of reirradiation studies have been published since the 

overview in Seminars in Radiation Oncology 2000 (Nieder C, Milas L, Ang 

KK). The experimental basis largely was already provided before that date. 

Results from animal models suggest that acute reactions in the reirradiation 

setting to not differ significantly from those observed in first-line treatment. 

While lung and spinal cord recover from occult damage to a considerable 

extent during the interval between two radiotherapy series, no recovery was 

observed for heart, kidney and bladder. These findings have important implications 

for the development of late toxicity after reirradiation. Clinical data 

confirm the ability of the spinal cord to tolerate reirradiation to certain dose 

levels and a risk score that can be used to estimate the risk of myelopathy 

has recently been published. In palliative settings, reirradiation has successfully 

been used in patients with glioma, brain metastases, bone metastases, 

lung cancer, head and neck cancer, recurrent breast cancer and pelvic malignancies. 

Curative approaches for selected patients, e.g., with head and 

neck cancer and prostate cancer appear to exist. Recently, IMRT, stereotactic 

radiotherapy and brachytherapy have increasingly been used, as highly conformal 

dose distributions might reduce the risk of normal tissue reactions. In 

addition, chemotherapy and hyperthermia were studied, as combined modality 

treatment might increase local control when radiation dose escalation is 

not feasible. Typically, target volumes do not include elective lymph node areas 

in order to reduce normal tissue exposure. Increasing evidence supports 

the administration of reirradiation in various palliative and curative settings. 

However, randomized controlled trials are largely lacking and therefore many 

open questions, e.g., regarding optimal patient selection, fractionation and 

combination with other treatments remain. In many institutions, reirradiation 

is provided on a highly individualised basis where previous dose, volume, 

treatment response and side effects as well as time interval, disease extent, 

prognosis, comorbidity, tissue tolerance and presumed quality of life are taken 

into consideration. 

370 speaker 

NEW IRRADIATION TECHNIQUES FOR BREAST CANCER 

A. Fourquet 1 

1 INSTITUT CURIE, Paris, France 


Symposium 

S 123 

MAESTRO European Project: Innovations for 

planning and delivering of the RT treatment 

371 speaker 

INTRODUCTION TO THE MAESTRO SESSION (METHODS AND 

ADVANCED EQUIPMENT FOR SIMULATION AND TREATMENT IN 

RADIO-ONCOLOGY) 

R. Hugon 1 

1 CEA, Gif-sur-Yvette, France 

The integrated project MAESTRO proposes innovative research in the framework 

of the fight against cancer by developing practical solutions in the field 

of external radiotherapy. As a major concern of radiotherapy is to deliver the 

most conformational dose while sparing healthy tissues, MAESTRO aims at 

providing more precise tools, quicker calculation means, appropriate quality 

assurance devices, and in particular at helping novel technologies to spread, 

like Intensity-Modulated Radiation Therapy (IMRT), Image-Guided Radiation 

Therapy (IGRT) and Proton-therapy. Lasting from May 2004 to October 2009 

and coordinated by CEA (France), MAESTRO involves 25 partners from 9 

European countries, including : - research institutes which develop the devices, 

- clinics which provide technical requirements and advices, and perform 

the tests of devices developed within Maestro in clinical environment, 

- industrial companies which have the mission to industrialize the devices. 

The technical developments are split into scientific work-packages (WP) : a) 

Adaptive radiation delivery : The goal is to increase treatment precision by 

tracking organ motions and altering patient positioning in real time. b) Development 

by IBA of a proton beam head working in the Pencil Beam Scanning 

(PBS) mode, making treatment more accurate, reducing collateral damage to 

healthy tissues and minimizing proton production. c) Radiation therapy software 

development, aiming at preparing more precise treatments more quickly 

: multimodality image registration and automatic segmentation of organs at 

risk based on anatomical atlas, Monte-Carlo-based calculation of the dose 

distribution for electron and photon beams. These modules are being integrated 

into the Dosisoft’s treatment planning system. d) Sensors for dose 

evaluation, devoted to better control of the dose delivered by the treatment : 

within this WP various technologies of point, 2D and 3D dosimeters are designed 

and developed. They are intended to pre-treatment dose verification 

and in vivo dose measurement. Scanditronix already markets 2D detectors 

developed within MAESTRO. A WP dedicated to the clinical activities insures 

that the devices developed within MAESTRO meet the clinical requirements. 

It also includes the development of a dose risk assessment module (second 

cancer induction risk) based on the assessment of the out-of-field dose distribution, 

the goal of which is to help the choice of best treatment parameters 

and modality. 

372 speaker 

FULLY AUTOMATIC SEGMENTATION OF BRAIN, HEAD AND NECK, 

AND PELVIS OAR 

A. Guimond 1 , P. Y. Bondiau 2 , O. Commowick 3 , V. Grégoire 4 , J. Costa 5 , 

H. Delingette 5 , A. Isambert 6 , J. B. Ruaud 1 , G. Malandain 5 

1 DOSISOFT, Cachan, France 

2 CENTRE ANTOINE-LACASSAGNE, Radiotherapy, Nice, France 

3 DOSISOFT / INRIA, Cachan, France 


Experimental Radiotherapy , Brussels, Belgium 

5 INRIA, Asclépios, Sophia Antipolis, France 

6 INSTITUT GUSTAVE-ROUSSY, Physics, Villejuif, France 

Radiotherapy planning requires accurate delineations of the tumor and of the 

critical structures. Atlas-based segmentation has been shown to be very efficient 

to automatically delineate these structures. Different atlas construction 

methodologies can be designed, and can be divided into image based 

atlases and shape based atlas. Their choice depends on the expected difficulties 

to warp the atlas onto a patient image. An image based atlas is 

made of a couple of images representing the same subject, one medical image 

of the modality to be processed (e.g. MRI or CT) and one labels image 

which defined the critical structures. Atlas-based segmentation is then 

achieved by non-linearly registering the first image onto the patient’s image 

to be contoured, and by applying the calculated deformation to the labels’ 

image. Building an atlas consists then in obtaining a medical image together 

with its segmentation. It can be achieved first by segmenting carefully a given 

subject. This approach has been investigated for the cerebral critical structures 

in (Bondiau, IJROBP 2004), where an artificial 3D MR image has been 

manually segmented. The atlas-based segmentation yields average sensitivity 

and specificity of respectively 0.76 and 0.97. However, using an individual 

to build the atlas may introduce bias since this individual may not be representative 

of the patients’ population. This point can be addressed by computing 

a virtual average subject from a whole population already segmented (one 

may reuse treatment planning contours and images of a treated population), 

which implies calculating both an average medical image and average con-

S 124 SYMPOSIUM WEDNESDAY, SEPTEMBER 17, 2008 

tours. This approach has been investigated for the critical structures in the 

head and neck localization (Commowick, RO 2008) with average sensitivity 

and specificity of respectively 0.82 and 0.86. A shape based atlas is made of 

a medical image with attached deformable shapes of the critical structures. 

A first registration of the medical image with the patient’s image allows to 

roughly align the shapes with the structures to be delineated. Then, based 

on the image information, these shapes are deformed to adapt themselves 

to the structures contours (Costa, ISBI 2007). These atlases have been implemented 

and validated in the DOSIsoft ISOgray product (Isambert, ESTRO 

2007 and RO 2007). 

373 speaker 

MONTE CARLO PENELOPE CODE INTEGRATED INTO A TPS FOR 

DAILY CLINICAL USE: FROM MYTH TO REALITY 

F. Husson 1 , F. Salvat 2 , A. Isambert 3 , S. Morrow 1 , E. Franchisseur 1 

1 DOSISOFT S.A., TPS radiotherapy, Cachan, France 

2 UNIVERSITAT DE BARCELONA, Barcelona, Spain 

3 INSTITUT GUSTAVE ROUSSY, Radiotherapy, Villejuif, France 

The Monte Carlo (MC) method allows calculating accurate dose distributions 

for clinical radiotherapy, particularly in heterogeneous patient tissues where 

the effects of electron transport cannot be accurately handled with conventional, 

deterministic dose algorithms. With the development of faster codes 

optimised for radiotherapy calculations and improvements in computer processor 

technology, the Dosisoft company is currently releasing Penelope 

based MC algorithms for photon and electron beam treatment planning in 

the Isogray system. Firstly, the original PENELOPE MC code (F.SALVAT, 

Barcelona University) has been sped up and adapted to voxelised geometries. 

As a simplification, aspects of the physics not relevant in the energy 

range of medical applications have been pruned. The resulting PENFAST 

code is a fast MC code version implemented in the software package allowing 

the management of dose calculation in CT-patient exams. Secondly, the 

method used for clinical dose calculations with MC simulation is quite different 

from conventional algorithms and many features are unique components of a 

MC system: accelerator treatment head simulation and beam modelling, CTto-material 

conversion and anatomical description of the patient, statistical 

uncertainties, voxel-size and processing-time effects on calculation results, 

dose-prescription and monitor-unit calculation& Some of these issues are 

discussed and details of their implementation in Isogray are presented. For 

a successful implementation of the MC method in a radiotherapy treatment 

planning system, new approaches particularly for beam commissioning, patient 

modelling, dose reporting and verification calculations are encouraged. 

In addition, the specific issues associated with MC systems require educational 

efforts for both developers and end-users to ensure that patient dose 

calculations are effected safely. 

374 speaker 

NEW COUCH BASED CONTROL SYSTEM FOR AUTOMATIC INTER 

AND INTRA FRACTION PATIENT MOTION COMPENSATION FOR 

IGRT 

O. Haas 1 , P. Skworcow 1 , A. Sahih 1 , I. Land 2 , D. Paluszczyszyn 1 , J. Mills 

2 , G. Bueno 3 , M. Fisher 4 

1 

COVENTRY UNIVERSITY, Control Theory and Applications Centre, 

Coventry, United Kingdom 

2 

UNIVERSITY HOSPITALS COVENTRY AND WARWICKSHIRE NHS TRUST, 

Department of Clinical Physics and Bioengineering, 

Kingdom 

Coventry, United 

3 

UNIVERSITY OF CASTILLA-LA-MANCHA, Ciudad Real, Spain 

4 

UNIVERSITY OF EAST ANGLIA, Norfolk, United Kingdom 

Purpose/Objectif: To design, implement and evaluate on a clinical patient 

support system (PSS) a new predictive control strategy to position automatically 

patient before each fraction and compensate for intra-fractional organ 

motion. 

Materials/Methods: Elekta, Siemens and Varian PSS and table tops performances 

in terms of speed, accuracy and mechanical deflection were assessed. 

The PSS limitations were taken into account to design a new IGRT 

controller that could be interfaced with current PSS to automatically position 

patient and compensate for breathing motion during radiation delivery. The 

novelty of the approach lies in the exploitation of the predicted organ motion 

and the limitations associated with the velocity and torque available on standard 

PSS to calculate a control action able to accommodate PSS dynamics 

and video tracking delays. The performances of neural networks, linear and 

nonlinear filters as well as interactive multiple models to predict organ/patient 

motion were assessed. Interfraction motion was detected using geometrical 

active contour applied to CT and video sequence. Intrafractional patient motion 

was measured two IEEE1394 cameras using a video tracking system 

implemented in LabVIEW using an NI6024E data acquisition card to communicate 

to the control system the target locations sent by. A rapid prototyping 

approach was used to design, develop and implement the control system on a 

clinical PSS. The control system was programmed in C, Matlab and Simulink 

and implemented onto the dSPACE R&D Controller Board DS1104. The latter 

was connected to the PSS joystick and sensors. The performance of the new 

tracking system was evaluated by assessing, in terms of root mean square 

the error between the true trajectory and the actual trajectory, the ability of 

the PSS to follow a range simulated patient motion as well as compensate for 

the motion of a purpose built phantoms. 

Results: The video tracking system has a sub-millimetre resolution for a 

tracking envelope of 50mm x 50mm x 50mm with a sampling frequency between 

15 and 60Hz. The motion prediction algorithm are able to predict motion 

changes from 0.1s up to 0.6s in advance with prediction accuracy ranging 

from 0.6 to 1.1mm (RMSE). Neural network performed best but Kalman filter 

was used for the practical demonstration due to ease of tuning. The MPC 

control system evaluated for a clinical PSS, see Figure 1, was shown to be 

able to follow a given trajectory with sub-millimetre accuracy. 

Conclusions: The new model predictive control system incorporating motion 

prediction and PSS constraints was demonstrated in practice and shown to 

be able to track realistic patient motion with sub-millimetre accuracy. Details 

of the motion detection, motion prediction and control system design can be 

found in [1]. 

Haas O.C.L. and Burnham K.J. (eds.), 2008, Intelligent and Adaptive Systems 

in Medicine. Boca Raton, Taylor & Francis.

WEDNESDAY, SEPTEMBER 17, 2008 TEACHING LECTURE 


375 speaker 

MOLECULAR DIAGNOSIS AND PREDICTION: GENOME WIDE 

METHODS AND POTENTIAL 

C. West 1 

1 UNIVERSITY OF MANCHESTER, Academic Radiation Oncology, Manch- 

ester, United Kingdom 

The draft sequence of the human genome was published in 2001 with the 

full sequence becoming available in April 2003. New high throughput technologies 

and capabilities have also become available for analysis of a large 

number of genes or the whole genome. This ’genomic revolution’ increases 

the possibility of future personalised treatment based on molecular profiling. 

For radiotherapy, radiogenomics and the characterisation of molecular profiles 

predicting radioresponse have evolved from previous predictive assay 

work involving predominantly cell-based tests. In general, the cell-based assays 

lack the sensitivity and specificity required for routine clinical use, but 

new technologies have the potential to be more comprehensive and robust. It 

is clear that the extent of the reaction of a tumour or normal tissue to ionising 

radiation depends on multiple factors and genes. We are moving away from 

the 20th century approach of measuring radiosensitivity, hypoxia or proliferation 

to a whole genome strategy that encompasses potentially all biological 

factors underlying patient differences in radioresponse. Testing multiple 

genes should therefore increase the chance of obtaining an accurate predictor. 

These genes can be investigated at the DNA (genome), RNA (transcriptome) 

or protein (proteome) level. For example, high throughput genotyping 

methods are available for the simultaneous investigation of genome wide single 

nucleotide polymorphisms. It is possible to examine the RNA transcription 

of every human gene. At the protein level, the increasing availability of antibodies 

and the development of tissue microarrays for investigating multiple 

samples will facilitate the development of molecular profiles based on protein 

expression. This progress in assay methods is associated with increased research 

in bioinformatics and advances in cluster analysis approaches, which 

are required for the development of molecular profiles. Thus, the genomic 

revolution and developments in high throughput technology has potential to 

enable us to predict patient response to radiotherapy. Future research should 

focus on increasing our understanding of the new tools in terms of radiobiologically 

valid phenotypes. Such research will be facilitated by embedding 

translational studies into radiotherapy trials associated with the collection of 

high quality physics, clinical and outcome data. 

376 speaker 

MR IMAGING TECHNOLOGY FOR RADIATION ONCOLOGY 

J. Kurhanewicz 1 

1 UCSF COMPREHENSIVE CANCER CENTER, San Francisco CA, USA 


377 speaker 

THE EVOLUTION OF LINAC TECHNOLOGY FOR STEREOTACTIC 

RADIOSURGERY 

T. Solberg 1 

1 UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, Radiation 

Oncology, Dallas, USA 

Stereotactic radiosurgery was pioneered by Lars Leksell In 1951. Over the 

ensuing years, high-dose irradiation of cranial neoplasms delivered in a single 

fraction has become a standard of care in the treatment brain tumors, vascular 

malformations, functional disorders, and pain. While the earliest applications 

utilized kilovoltage x-rays, Leksell later abandoned x-rays for protons, 

which offered superior dose localization properties. Throughout the 1960’s 

and 1970’s, thousands of patients were treated with proton radiosurgery, albeit 

at only a handful of institutions worldwide. Leksell subsequently developed 

the Gamma Knife, a technology which has treated over 400,000 patients 

to date. Despite demonstrated clinical success, technological shortcomings 

precluded the use of conventional linear accelerators in radiosurgery applications 

for several decades. In 1984, Osvaldo Betti described modifications to 

a conventional linac to enable radiosurgery. The standard couch, the weakest 

link for mechanical precision, was replaced by curved rails on which a 

special seat affixed with a stereotactic frame could travel. The device was 

later referred to (affectionately) as the "cyclothrone." The following year Federico 

Colombo reported on initial clinical results of linac radiosurgery for brain 

tumors and AVMs. His experience also included a small series of pediatric 

patients. The late 80’s saw continued development in technology for linacbased 

radiosurgery, stimulated primarily by groups in Boston and Gainesville. 

Over the last decades, linac radiosurgery has evolved at a rapid pace, producing: 

dedicated linac devices for stereotactic delivery, relocatable frames 

to facilitate fractionated delivery, "frameless" technologies, and the applica- 

S 125 

tion to extracranial tumor sites. The mid-90’s ushered in initial attempts at 

body radiosurgery, pioneered in two very different ways by groups in Sweden 

and in the U.S. In Stockholm, Ingmar Lax and Henric Blomgren developed 

the stereotactic body frame. The system consisted of an immobilization box 

with embedded CT fiducials, and a device for compressing the chest to limit 

respiratory motion. The Karolinska group has successfully treated thousands 

of patients for malignancies in the chest and abdomen, and the methodology 

has gone on to find broad acceptance at a number of centers worldwide. In 

contrast, the system described by Allan Hamilton at the University of Arizona 

was developed for the express purpose of treating spinal targets in a single 

fraction. The system consisted of a shallow rigid box, in which patients were 

placed in a prone position. Under anesthesia, small clamps were attached to 

one or two spinous processes adjacent to the intended target. These clamps 

were rigidly attached to two semicircular metal arches which were also used 

to define stereotactic coordinates. Imaging, planning and treatment were performed 

in a single setting with rigid fixation for the duration of the procedure. 

This prototype spinal system was subsequently used in the treatment of nine 

patients, all of whom had recurrent spinal disease. Doses prescribed were 

understandably conservative, ranging from 8 to 10 Gy. Spinal radiosurgery, 

now performed non-invasively with the aid of image guidance, is a rapidly 

growing modality for the treatment of benign and malignant disease. Much 

higher doses than those initially used by Hamilton can be delivered safely 

and effectively. Since its inception, linac radiosurgery has become a highly 

successful treatment for cranial and extracranial disease and continues to revolutionize 

the traditional fields of neurosurgery and radiation oncology. There 

are numerous benefits to such a paradigm, including improved patient outcomes 

and reduced healthcare costs. This presentation will review 25 years 

of progress in linac radiosurgery with a focus on current state-of-the-art and 

future directions. 

Evidence based medicine: CNS tumours 

378 speaker 

EVIDENCE-BASED MEDICINE ( EBM) : PRIMARY CNS TUMORS 

R. O. Mirimanoff 1 

1 CENTRE HOSPITALIER UNIV. VAUDOIS, Department of Radiation Oncology, 

Lausanne, Switzerland 

Purpose: To review the management of the most frequent primary CNS tumors 

from diagnosis to therapy, according to the best EBM data.Methods: 

Given the extraordinary variety of tumors that can affect the CNS, we will discuss 

only intra-axial lesions such as low-grade and high-grade glioma with 

some of their common pathological sub-groups or anatomical variants, the 

primary CNS lymphoma, and PNET or PNET-like tumors. For each tumor 

type we will summarize briefly some basic and new pathological features, 

including the increasing role of molecular genetic analysis, which can be relevant 

to diagnosis and therapy, we will address some specific current or innovative 

imaging techniques, and then we will focus on the respective role 

of surgery, radiation therapy (RT) and chemotherapy (CXT) or their combinations, 

whenever possible according to the most important and recent randomized 

phase III trials.Results : Low-grade glioma (LGG) or WHO I and II 

comprise a wide range of tumors from pure astrocytic to oligodendroglial to 

mixed components. Molecular pathology includes for example early PDGF 

overexpression and later a series of accumulated alterations which lead to 

increased malignancy. In the oligo type the characteristic alteration is a loss 

of chromosomes 1p and 19q with important prognostic implications. Surgery 

is the mainstay in symptomatic LGG patients ; RT improves progression-free 

(PFS) but not overall (OS) survival. High-dose RT is not superior and more 

toxic than moderate-dose RT (45-50Gy). The role of chemotherapy is still 

under investigation. High-grade glioma (HGG) or WHO III and IV include 

anaplastic astrocytoma, glioblastoma multiforme (GBM) and anaplastic oligodendroglioma, 

which should be studied separately due to large differences 

in pathology, genetic alterations and prognosis. For example GBM have a 

high frequency of overexpression of EGFR, of angiogenesis and LOH 10q. 

Surgery when feasible impacts on survival, and post-operative RT improves 

OS, but there is no evidence that doses higher than 60 Gy are any better. In 

elderly patients with a particularily poor OS, hypofractionated RT is equivalent 

to conventional RT. The addition of temozolomide (TMZ) to RT improves DFS 

and OS, especially in good prognostic categories (RPA III) and in tumors with 

the methylation of the promotor gene MGMT. The role of TMZ in anaplastic 

astrocytoma is under investigation. In anaplastic oligodendroglioma, CXT 

with PCV improves PFS but not OS, even when there is a 1p 19q loss. Primary 

CNS (or Primary Brain PBL) lymphoma can occur in immunocompetent 

or immunosupressed patients, with a key role of EBV virus for the latter. In 

80% of cases PBL belong to the large-cell diffuse B-cell lymphoma and rarely 

to the T-cell category. Contrarily to the peripheral lymphoma, PBL are not very 

radio-sensitive and even after whole brain RT to 40-50 Gy (which was the previous 

standard), OS was poor with 12-18 months median OS. RT combined to 

methotrexate (MTX)-based chemotherapy has yielded to improved survival, 

at the cost of severe neurotoxicity especially in elderly patients. Currently 

MTX-based CXT alone is the preferred treatment, with RT reserved to recurrence 

or progression, and seems to preserve better the cognitive functions. 

Contrarily to LGG, HGG and PBL, other tumor types or sites were rarely if


ever studied in controlled clinical trials, with the exception of children’s medulloblastoma. 

However we will also summarize some data regarding ependymoma, 

brainstem glioma, intraspinal tumors, and PNET.Conclusions: Primary 

CNS tumors, even when excluding extra-axial lesions, represent a very 

large group of tumors with widely different features regarding their biological 

behaviour, management and prognosis. As far as therapy is concerned, level 

I EBM is available only in some of the most frequent tumor types like highgrade 

and low-grade glioma, and only in a minority of the remaining ones. 

However, whatever the level of evidence, most studies confirm the central 

role of surgery and RT, and the emerging role of CXT with or without the 

other treatments. Specific molecular characteristics already play a role in the 

diagnosis and prognosis, and may help in the future for more individualized 

treatment’s choice. 

Symposium 

Is there still a role for radiotherapy in paediatric 

oncology? 

379 speaker 

THE SPECIFIC PROBLEMS WITH PEDIATRIC PATIENTS: MANAGE- 

MENT, ANAESTHESIA, IMMOBILISATION AND NEW RADIOTHER- 

APY TECHNIQUES 

A. Aitken 1 , F. Saran 2 , S. Helyer 1 , H. Taylor 1 

1 ROYAL MARSDEN HOSPITAL, Radiotherapy, Sutton, United Kingdom 

2 ROYAL MARSDEN HOSPITAL, Neuro-Oncology, Sutton, United Kingdom 

The delivery of radiotherapy to paediatric patients presents a unique challenge 

to clinical oncology. Given the rapid changes in technology and evolving 

clinical knowledge patient management, immobilisation, anaesthesia and 

treatment techniques are key issues that need to be constantly monitored, assessed, 

developed, and adapted. Optimal disease management is essential 

if the profound impact on the patient, both physiologically and psychologically, 

is to be minimised and needs to be performed in the setting of national and international 

agreed protocols. The radiotherapeutic management of paediatric 

patients requires the co-ordination of a multidisciplinary team. It is important 

that both the patient and carers receive sufficient support throughout their 

treatment pathway from all medical personnel involved. Patients requiring 

anaesthesia or sedation in order to overcome non-compliance provide additional 

challenges. This approach is complex, costly, time consuming and can 

induce further complications such as sleep disruption and sub-optimal nutrition. 

A difference of opinion between the preferred use of sedation or general 

anaesthesia is also still prevalent amongst different departments. Effective 

immobilisation is fundamental to the accurate delivery of radiotherapy and 

can aid in reducing random and systematic errors. Commercial systems offer 

accurate repositioning and immobilisation however; they may not be ideal 

for paediatric patients and could result in non-adherence or poor compliance. 

Further development of these systems may therefore be required. With improved 

technology comes the development of new techniques and the successful 

application of these technologies will be determined by the skill and 

expertise of the clinicians, physicists and radiographers involved. New technologies 

do offer the potential for therapeutic gain while sparing normal tissue. 

Any additional cost and effort is justifiable for possible long-term benefits 

associated with this patient group whose risk of long-term effects or the induction 

of secondary cancer must be considered. 

380 speaker 

CHANGING PRACTICE OF RADIOTHERAPY IN MEDULLOBLAS- 

TOMA 

F. Saran 1 , A. Aitken 1 , H. Taylor 1 

1 ROYAL MARSDEN NHS FOUNDATION TRUST, Radiotherapy, Sutton, United 

Kingdom 

MB (primitive neuroectodermal tumour (PNET) of the posterior fossa) is the 

commonest malignant CNS tumour of childhood and has a high propensity to 

spread through the cerebrospinal fluid. Surgery and radiotherapy (RT) to the 

craniospinal axis (CSRT) has been the fundamental treatment component to 

obtain long term cure. Our understanding and management of these tumours 

has substantially changed over the last 20 years due to a large number of consecutive 

prospective clinical trials in the paediatric setting. Progress has been 

made in pathology by identifying that anaplastic and large cell medulloblastomas 

carry a poorer prognosis similar to patients with metastatic disease at 

diagnosis. The standard of care in the past was to offer post-operative CSRT 

to a dose of 35 Gy followed by a boost to the posterior fossa of 20 Gy (cumulative 

dose 54 - 55 Gy). Average 3 year survival for patients with disease 

confined to the posterior fossa (standard risk, SR) was in the range of 60%. 

The quality of RT has a fundamental impact on outcome. Today treatment 

is age and risk dependent. In the infant setting the focus has been either to 

avoid RT entirely and/ or replace it with primary postoperative chemotherapeutic 

strategies. In the older patient group of SR patients (radiological residual 

disease < 1.5 cm on immediate postoperative imaging and the absence of 

metastases (M0)) the focus, both in Europe and the US, has been on a dose 

reduction of the CSRT component in combination with chemotherapy yielding 

3 year survival rates in the range of 80%. Only the French group has explored 

a RT only approach using hyperfractionation (M-SFOP 98) with similar survival 

rates. The management of high risk disease (evidence of metastases at 

presentation and / or unfavourable histopathology) remains a challenge. Conventional 

treatment strategies (surgery and radiotherapy) offer 5 year survival 

rates in the range of 35-40%. Some recently published phase II studies using 

combined modality approaches (including intensive chemotherapy) could 

potentially offer improved outcomes. The clinical experience suggests that 

the chemotherapy tolerance of "paediatric" regimes in the adult population is 

reduced. In addition, given the different pattern of recurrence, there is doubt 

if the underlying biology of paediatric and adult MB is identical. Thus, in the 

absence of prospective randomised clinical trials with underpinning biological 

studies, it remains to be proven if treatment strategies derived from the


paediatric experience can be directly translated into adult practice. 

381 speaker 

ADVANCES IN THE MANAGEMENT OF EWING’S SARCOMA 

T. Björk-Eriksson 1 

1 SAHLGRENSKA UNIVERSITY HOSPITAL, Department of Oncology, Göte- 

borg, Sweden 

Ewings sarcoma (ES) is the second most common primary bone tumour seen 

in children and adolescents, first described by James Ewing in 1921. ES are 

high grade malignancies consisting of primitive, small, blue round cells that 

exhibit varying degrees of neural differentiation. ES occur predominantly in 

bone but may also present as primary soft tissue lesions (extra-osseous Ewings 

sarcoma, Askin tumour and malignant peripheral neuroectodermal tumour) 

and very rarely in visceral organs. Almost all of the Ewing sarcoma 

family tumours are characterised by a re-arrangement of chromosome 22, 

most common in the form of an 11;22 translocation leading to formation of 

the EWS_FLI-1 fusion gene. ES are highly aggressive tumours with approximately 

25% presenting with metastatic disease. ES was early on discovered 

to be very radiation sensitive, however, without systemic treatment more then 

90 % of patients died from secondary metastasis. Today ES is therefore 

considered to be a systemic disease necessitating local as well as systemic 

treatment. During the last 40 years an aggressive multidisciplinary approach 

has resulted in significantly improved prognosis. The improved outcome is not 

only due to refined treatment but also due to improved diagnostic tools (immunohistochemistry 

and cytogenetic/molecular genetic techniques), refined 

assessment of treatment response and new imaging techniques (CT, MRI 

and PET) leading to a more precise diagnosis and risk stratification. This 

means that a more individualized treatment can be offered to patients with 

ES. According to chemotherapy new drugs and dose intensified treatment 

with up-front supportive care including e.g. cytokines and antibiotics has contributed 

to better results. Improved understanding of the role of surgery in 

ES treatment has led not only to better survival but also to organ- and function 

sparing surgical techniques. With regard to radiation therapy, patients 

with ES has gained from e.g. higher photon energies, alternative fractionation, 

improved definition of targets, brachyterapi, new treatment techniques 

like intensity modulated radiotherapy (IMRT) and particle therapy. Besides 

this, improvements in follow-up, new fertility sparing techniques together with 

patient- and family support should be mentioned as factors contributing to 

improved treatment results in terms of event-free survival, overall survival 

and improved quality of life. There is, however, still a strong need for further 

improvement of treatment results, both in terms of local recurrent disease, 

survival and side-effects including e.g. secondary malignancies. 

Tailoring for breast cancer radiotherapy 

382 speaker 

WHICH WOMEN REMAIN AT SIGNIFICANT RISK OF LOCAL 

RELAPSE? 

E. Senkus-Konefka 1 

1 MEDICAL UNIVERSITY OF GDANSK, Department of Oncology and 

Radiotherapy, Gdansk, Poland 

Data from the 2005 Early Breast Cancer Trialists Cooperative Group overview 

suggest a direct impact of loco-regional relapse on the risk of breast cancer 

death: it is estimated that one of four loco-regional relapses will result in additional 

breast cancer death. Radiotherapy is an effective method allowing 

for prevention of approximately of these relapses; however at the expense 

of considerable toxicity and possibly increased non-cancer related mortality. 

Thus, identification of patients at significant risk of loco-regional relapse, 

which may derive most benefit from postoperative radiotherapy, remains of utmost 

importance. Additionally, improving efficacy of systemic adjuvant treatments, 

allowing for better control of subclinical systemic disease, may actually 

underscore the need for more effective local treatments. Traditionally radiotherapy 

was applied to patients with estimated > 20% risk of loco-regional 

relapse, i.e. those with T3 tumors and/or involvement of >3 axillary lymph 

nodes. Data from randomized clinical studies on adjuvant radiotherapy suggest, 

however, that significant benefit can also be achieved in patients traditionally 

considered to be of intermediate recurrence risk. This group includes 

patients with involvement of 1-3 lymph nodes and/or large, high-grade grade, 

endocrine non-responsive tumors. Predictors of high risk of loco-regional relapse 

include also younger age, medial location of primary, lymphovascular 

invasion, involvement of >25% of removed nodes, large diameter of nodal 

metastases and their extracapsular extension. On the other hand, some subpopulations 

of patients traditionally included in "high-risk" group may actually 

have the risk of loco-regional recurrence low enough to justify omission of radiotherapy. 

Examples of such patients include endocrine responsive tumors 

with involvement of > 4 lymph nodes or pT3N0 patients treated with mastectomy. 

The discriminatory value of "traditional" prognostic and predictive 

risk factors is, however, limited and most likely will not improve markedly in 

S 127 

the future. Further refinements allowing for treatment individualization may be 

expected as a result of recent developments in molecular biology. Techniques 

such as gene expression assays using DNA microarray technology may allow 

for identification of gene signatures providing more precise prognostic or 

predictive information. 

383 speaker 

WHAT IS THE CLINICAL RATIONALE FOR DOSE INTENSIFICA- 

TION? 

J. R. Yarnold 1 

1 THE ROYAL MARSDEN NHS FOUNDATION TRUST, Academic Unit of 

Radiotherapy, Sutton, United Kingdom 

The standard approach to dose intensification in women with early breast 

cancer treated by breast conservation surgery involves a shrinking field technique 

delivering a sequential boost dose of 16 Gy in 2.0 Gy fractions to the 

tumour bed following whole breast radiotherapy to 50 Gy in 25 fractions over 

a total of 6.6 weeks. In high risk subgroups, with local relapse risk 10% at 

10 years despite optimal surgery, systemic therapy and standard radiotherapy, 

the case for dose intensification assumes that the excess local relapses 

risk is localised within an identifiable partial breast (boost) volume. Published 

data are consistent with this assumption, although the precision with which 

local relapse can be localised within the boost volume without internal fiducial 

markers and 3D reconstruction is uncertain. Assuming that radiation resistance 

is a significant factor in high risk subgroups, dose intensification is a 

rational approach. A 16 Gy boost dose to the tumour bed halves the risk of 

local relapse, corresponding to a g value of about 0.5 (% increase in local 

control per % increase in dose given in 2 Gy fractions). In the adjuvant context, 

the dose response is log-linear rather than sigmoid, so the g value offers 

a reasonable guide to further modest gains from dose intensification even 

at levels of local control > 90%. The dose response for late adverse effects 

is steeper than this (g value of 2), but the impact on morbidity is expected 

to be less than after whole breast radiotherapy due to the smaller volumes 

irradiated, especially if conventional or novel brachytherapy techniques are 

employed. A further consideration relates to clinical trials of hypofractionation 

that suggest no disadvantage to this approach with external beam radiotherapy. 

This raises opportunities for dose intensification using techniques of 

intensity modulated radiotherapy that modulates fraction size in preference to 

fraction number. This approach is under test in the UK IMPORT High Trial 

comparing sequential and concurrent boost in women at higher than average 

local relapse risk. 

384 speaker 

HOW TO DEFINE THE TARGET VOLUME ? 

L. Boersma 1 , P. Poortmans 2 

1 UNIVERSITY HOSPITAL MAASTRICHT, MAASTRO CLINIC, Radiation 

Oncology, Maastricht, Netherlands 

2 BERNARD VERBEETEN INSTITUUT, Radiation Oncology, Tilburg, Nether- 

lands 

Background and aim: CT-based treatment planning for breast radiotherapy 

(RT) may allow more accurate delineation of the CTV. However, this is not 

standardized and may result in larger irradiated volumes. The challenges 

and strategies for target volume delineation for the breast and the boost will 

be discussed. 

Challenges: The CTV-breast includes the entire amount of glandular tissue. 

Especially for older patients, this is however not well visible on a CT-scan. 

When delineation is based on palpation and a PTV margin is added, the irradiated 

volume increases beyond the conventional one, without any clinical 

arguments to sustain this enlargement. The CTV-boost is defined as the rim 

of tissue within 1 to 2 cm of the primary tumor. Obviously, as demonstrated 

by the large interobserver variation reported for CTV-boost delineation, it is 

quite challenging to reconstruct this on the post-operative planning CT. First, 

the excision cavity is not always clearly visible. Consequently, localization of 

the CTV-boost depends on clips and pre-operative clinical information, which 

is however mostly not available with the patient in RT position. Moreover, the 

excision cavity is shown to change and shrink after surgery, making it even 

more doubtful whether it is safe to delineate based only on the shrunken excision 

cavity. Finally, accurate information on free margins in 3D is usually 

lacking, such that isotropic margins of 1 to 2 cm around the excision cavity 

are needed. This strategy leads to 1.6-1.8 fold larger irradiated volumes than 

with conventional simulation. 

Strategies: Based on information from palpation and visible glandular tissue, 

the CTV-breast can be delineated. The treatment fields, conventionally positioned 

based on clinical information, can than be adapted to the CTV-breast 

as well as to the heart, the lungs and the primary tumor bed. If necessary, the 

outer medial and/or lateral margins of the CTV-breast can be compromised, 

provided that the PTV-boost is still adequately covered. Delineation of the 

CTV-boost will be improved by pre-operative imaging in RT position. In addition, 

3D information on the resection margins reduces the irradiated boost 

volume with about 40%. The size of the excision cavity can be decreased


by choosing an appropriate surgical technique, or by increasing the time between 

surgery and planning-CT. Another approach to reduce the irradiated 

boost volume is to apply a simultaneously integrated boost technique. 

Conclusions: The introduction of CT-based treatment planning in breast RT 

allows more accurate delineation of CTV-breast and CTV-boost. However, a 

large inter-observer variation is seen, and CT-based delineation leads to an 

increase of the irradiated volumes. Currently, no data are available that show 

that more accurate CT-based delineation improves local control. Nevertheless, 

there are several strategies available to improve both CTV-breast and 

CTV-boost delineation leading to a decrease in interobserver variation. 

ESMO/ESSO/ESTRO - State of the art in the management 

of rectal cancer I 

385 speaker 

WHAT DO WE GET TO KNOW FROM THE PATHOLOGIST? 

N. Scott 1 

1 ST JAMES UNIVERSITY HOSPITAL, Pathology, LEEDS, United 

Kingdom 

The effective management of rectal cancer, early or advanced, requires a 

multi-disciplinary team approach in which the histopathologist plays a vital 

part. Pathological examination of the excision specimen can help determine 

prognosis, predict where recurrence is likely to occur, measure how responsive 

a tumour is to radiotherapy or chemotherapy and help audit both radiological 

and surgical technique. Recent key developments in pathological 

practise such as examination of the radial resection margin, mesorectal grading 

and features of the irradiated rectal cancer specimen will be covered in 

this presentation to illustrate the difficulties they pose and what insights they 

give to the behaviour of this common tumour. 

386 speaker 

MRI: STAGING AND RE-STAGING AFTER PREOPERATIVE TREAT- 

MENT, NEW CONTRAST AGENTS 

G. Brown 1 

1 ROYAL MARSDEN HOSPITAL, Radiology, London, United Kingdom 

This lecture will provide a review of : " Prognostic features identified using 

MRI " The value of MRI in patient selection for preoperative therapy " MRI for 

planning treatment volumes " Assessment of response after radiotherapy or 

chemoradiotherapy " Potential new tools for tumour evaluation such as functional 

imaging and novel contrast agents The ability to define the preoperative 

prognostic factors that predict for local and/or distant failure has made it possible 

to tailor preoperative strategies according to the detailed staging information 

afforded by high resolution techniques. A critical role of the technique 

is identifying patients at high risk of local recurrence based on relationship of 

tumour to the potential mesorectal surgical resection margin and also on the 

anatomical location of tumours with respect to the sphincter complex. The 

criteria for identifying potential margin involvement have been validated in the 

multi-centre setting and standardization of techniques and reporting criteria 

have been shown to be critical in obtaining consistently accurate results. The 

technique can be used to assess tumour response before and after preoperative 

chemoradiotherapy and can be used to help to plan surgery particularly 

using the baseline ands post treatment scans as a reference. In assessing 

response it is important to document the degree of regression of tumour away 

from the potential margin as well as the post treatment stage of the tumour 

and careful correlation with adequately sampled pathological assessment is 

required. The use of MRI in the evaluation of apparent complete clinical response 

is being evaluated in a phase II trial and how functional imaging techniques 

may be used as a surveillance method in patients wishing to defer 

surgery following chemoradiotherapy and potential complete response. 

387 speaker 

THE CONCEPT OF RADICAL SURGERY IN RECTAL CANCER 

T. Wiggers 1 

1 UNIVERSITY MEDICAL CENTER GRONINGEN, Department of Surgical 


Only a limited numbers of primary rectal tumors (T1) can be treated with a 

local excision . For the remaining tumors the concept of a radical resection 

with the endopelvic fascia as the anatomical border has been developed over 

the last twenty years. The introduction of this so called total mesorectal excision 

has reduced the local recurrence rate to 10%. The combination with 

a short course of preoperative radiotherapy has further reduced the recurrence 

rate to 5 percent . However this reduction has resulted in serious late 

side effects . In case of a threatened circumferential margin primary resection 

of the tumor will result in a high percentage of an involved margin with 

a subsequent high local recurrence rate even if pretreated with short course 

radiotherapy . The TNM classification is not sufficient to make the distinction 

between primary resectable cases and patients in need of neoadjuvant 

treatment . To define the concept of radical rectal surgery in combination with 

preoperative chemoradiation the following definition will be used for locally 

advanced rectal cancers: Any T4, any T3 with a predicted margin of less than 

1 millimeter to the endopelvic fascia, any lymph node outside the TME field. 

Modern imaging techniques are necessary for accurate assessment of rectal 

tumors since digital examination only is inferior . In nearly all cases staging 

with Magnetic Resonance Imaging (MRI) is mandatory since it gives a more 

optimal insight in the local tumor extension . Improvement of lymph node 

staging within and outside the rectal envelope may be expected with the introduction 

ultra small super paramagnetic iron oxides (USPIO)-enhanced MRI 

. After staging four groups of tumors can be distinguished: tumors with limited 

growth into the mesorectal fat, tumors with extensive tumor growth towards 

the endopelvic fascia but within the mesorectal envelope (including pathological 

lymph nodes), tumors invading adjacent structures but with growth limited 

to the pelvis and tumors with metastatic extra-pelvic disease (liver, lung, 

para-aortic and/or inguinal). In the first situation it remains questionable if 

besides radical excision preoperative radiotherapy is always mandatory. Both 

the Dutch and English study show an advantage in respect to local tumor 

control but the numbers needed to treat in relation to the numbers treated 

to harm make the choice often difficult. In the second and third situation 

neoadjuvant radiotherapy (dose between 45 and 50 Gray) with a 5-FU based 

chemotherapy as a radio sensitizer should be considered as standard therapy 

. The question is still open if intensifying chemotherapy with the addition of a 

second drug will increase downsizing and down staging without an increase 

of toxicity . After a waiting period of at least six weeks a TME resection may 

be performed in case of tumor confined to the pelvic envelope (even with autonomic 

plexus and sphincter sparing). In case of T4 tumors the operative


procedure should exist in more extensive "en bloc" resections with the extent 

mainly based on the primary imaging. This may include lateral side wall resections 

and excision of involved organs. If an abdomino perineal resection is 

necessary a wide local resection with complete removal of the levator muscle 

has become standard . Tailored made decisions have to be made in case 

of synchronous extra-pelvic lymph node or distant metastases. Usually induction 

chemotherapy is necessary for making a distinction between patients 

with or without a good prognosis based on the response . Summarizing it 

has become clear that identification of extent of tumor growth in rectal tumors 

is based on image guided staging. Based on this outcome radical surgery 

aiming on a R0 resection is in nearly all cases possible. 

Tumor microenvironment and radiation response 

388 speaker 

NITRIC OXIDE: TUMOR ANGIOGENESIS VS RADIOSENSITIZATION 

O. Feron 1 

1 UCL, Unit of Pharmacology and Therapeutics, Brussels, Belgium 

The biological status of nitrite recently evolved from an inactive end-product 

of nitric oxide (NO) catabolism to the largest intravascular and tissue storage 

of NO. While low pO2 favors enzymatic reconversion of nitrite into NO, 

low pH supports a non-enzymatic pathway. Since hypoxia and acidity are 

characteristics of the tumor microenvironment, nitrite could preferentially lead 

to NO production in tumors. Furthermore, the recent identification of eNOS 

as a potential nitrite reductase supports an active role of the downregulation 

of caveolin (normally involved in an inhibitory interaction with eNOS) in the 

enhanced capacity of tumor endothelial cells to produce NO. Here, we will 

report (i) how nitrite administration could influence response to radiotherapy 

through modulation of tumor oxygenation and (ii) how the lack of caveolin 

observed in the tumor vasculature is a favorable ground for nitrite-driven tumor 

angiogenesis. This work opens new perspectives for the use of nitrite 

as a safe and clinically applicable radiosensitizing modality and confirms the 

therapeutic value of the modulation of caveolin expression to interfere with 

nitrite-driven tumor angiogenesis. 

389 speaker 

ROLE OF LOX IN HYPOXIA-INDUCED METASTASIS 

J. Erler 1 

1 STANFORD UNIVERSITY SCHOOL OF MEDICINE, Stanford, USA 

All solid tumours contain regions of hypoxia. Tumour hypoxia is clinically associated 

with metastases and decreased survival, and hypoxic tumour cells 

have increased invasive and metastatic potential. We recently identified lysyl 

oxidase (LOX) as a hypoxia-induced gene that is essential for breast cancer 

metastasis [Erler et al, Nature, 2006]. LOX is a secreted amine oxidase that 

initiates the cross-linking of collagens and elastins in the extracellular matrix 

(ECM). Patients with elevated LOX expression have significantly decreased 

metastasis-free and overall survival. We showed that hypoxia-induced LOX 

activity in the ECM enables invasion through effects on cell-matrix adhesion 

and focal adhesion kinase activity. We now demonstrate that LOX secreted 

by hypoxic cells at the primary tumour is required for the formation of the premetastatic 

niche [Kaplan et al, Nature, 2005], which is necessary to support 

metastatic tumour growth.Using orthotopic models of breast cancer, we found 

LOX to be associated with fibronectin at distant sites of future metastasis. 

Bone marrow-derived cells (BMDCs) were recruited to these sites creating a 

niche permissive to the growth of metastasising tumour cells. LOX inhibition 

prevented BMDC recruitment and pre-metastatic niche formation, abrogating 

metastatic progression. We observed decreased LOX activity levels in the 

blood concomitant with the presence of distant metastases, and this association 

was confirmed in human cancer patients. Injection of mice with conditioned 

media (CM) from hypoxic wild type tumour cells supported metastatic 

growth of primary tumour cells expressing shRNA to LOX, which do not normally 

metastasize. This could be prevented by LOX inhibition, and restored 

by supplement of purified LOX. Injection of non-tumour bearing mice with CM 

from hypoxic wild type tumour cells resulted in recruitment of BMDCs to distant 

sites of future metastasis and formation of the pre-metastatic niche. This 

was also prevented by LOX inhibition, and restored by supplement of purified 

LOX. Importantly, LOX-dependent BMDC recruitment was demonstrated in 

both immuno-compromised and immune-proficient mice. We are the first to 

identify a protein secreted by the primary tumour that is directly involved in 

pre-metastatic niche formation. Our data suggest that targeting the niche is a 

valid therapeutic approach to prevent metastasis, and suggest LOX secreted 

by hypoxic tumour cells as a good therapeutic target. Furthermore, we show 

that LOX activity levels in the blood are associated with the development of 

metastases, and may be used to predict patient outcome. 

390 speaker 

S 129 

TARGETING TRANSLATIONAL CONTROL PATHWAYS IN HYPOXIC 

CELLS SENSITIZES TUMORS TO IRRADIATION 

K. Rouschop 1 , L. Dubois 1 , T. van den Beucken 2 , H. Niessen 3 , K. 

Savelkouls 1 , J. Bussink 4 , H. Mujcic 1 , W. Landuyt 5 , P. Lambin 1 , A. van 

der Kogel 4 , M. Koritzinsky 2 , B. Wouters 2 

1 

GROW RESEARCH INSTITUTE, MAASTRICHT UNIVERSITY, Maastro, 


2 

UNIVERSITY OF TORONTO ONTARIO CANCER INSTITUTE/PRINCESS 

MARGARET HOSPITAL, UNIVE, Department of Radiation Oncology, Toronto, 

Canada 

3 

GROW RESEARCH INSTITUTE, MAASTRICHT UNIVERSITY, Department of 

molecular genetics, Maastricht, Netherlands 

4 



5 

K.U. LEUVEN, GASTHUISBERG-CDG, Laboratory of Experimental 

Oncology/Radiobiology, Leuven, Belgium 

Hypoxia is a common feature of tumors that contributes to malignancy and 

treatment resistance. The basis for these effects derives in part through a 

transcriptional response mediated by the hypoxia inducible factor (HIF) family 

of transcription factors. In addition, we have shown that hypoxia influences 

mRNA translation by activation of the PERK kinase/integrated stress 

response (ISR) arm of the unfolded protein response (UPR). We established 

a new tumor model that allows therapeutic evaluation of targeting these pathways 

within an identical genetic background. Cell lines were engineered to 

accept transgenes encoding dominant negative or mir30 based RNAi targeting 

various components of the HIF and ISR pathways. To mimic the clinical 

situation, transgene expression was regulated by doxycycline such that the 

pathways could be targeted after tumors were established. Consistent with 

previous studies with knockout cell lines, targeting the ISR resulted in significant 

sensitization to hypoxia induced cell death. In wild type cells we discovered 

that the ISR regulates autophagy as a survival mechanism during 

hypoxia. Furthermore, inhibition of autophagy sensitized cells to hypoxia by 

decreasing proliferation and clonogenic capacity. In vivo, targeting the HIF or 

ISR pathways after tumor establishment had little or no effect on overall tumor 

growth. However, targeting the ISR resulted in a significant increase in tumor 

growth delay after radiation therapy. Hypoxic tumor areas stained positive 

for markers of autophagy and pharmacological inhibition of this pathway also 

sensitized tumors to irradiation. These data suggest that the ISR contributes 

to hypoxic tolerance in vivo by regulating autophagy and that this pathway is 

an interesting therapeutic target in combination with radiotherapy. 

4D RT and respiratory gating 

391 speaker 

DECISION MAKING AND PLANNING STRATEGY IN 4D RADIO- 

THERAPY. 

H. McNair 1 

1 ROYAL MARSDEN NHS FOUNDATION TRUST, Radiotherapy, London, 


Lung tumour motion is one of the major challenges in radiotherapy treatment. 

The application of 4D radiotherapy in planning and treatment of lung cancer 

patients has the potential to overcome or compensate for, the problem 

of motion. The technique strategies used include breath hold, voluntary or 

controlled, using surrogates for tumour position either implanted markers or 

abdominal markers, or using margins to include magnitude of motion. To apply 

these techniques effectively and efficiently ideally requires choosing the 

method of planning and delivery with respect to individual patients characteristics, 

methods of immobilisation and the fractionation and dose regime to be 

used. However to predict or even assess the magnitude and reproducibility 

of the patient’s breathing pattern and tumour motion is complex. To make a 

decision regarding patients treatment the question remains as to whether a 

threshold be identified as to which patients benefit most, tolerate the technique 

and maintain reproducibility. This paper will attempt to address these 

issues when preparing a patient to receive radiotherapy for lung cancer . 

392 speaker 

CLINICAL CASE: LUNG - THE NEED FOR INDIVIDUAL MARGIN 

ASSIGNMENT USING 4D CT SCANS AND THE REDUNDANCY OF 

RESPIRATORY GATED TREATMENT 

J. Wolthaus 1 , J. J. Sonke 1 , V. Mexner 1 , M. van Herk 1 , M. Rossi 1 , J. 

Belderbos 1 , J. Lebesque 1 , E. Damen 1 


HOSPITAL, Radiation Oncology , Amsterdam, Netherlands


Respiratory motion causes imaging artifacts in conventional 3D freebreathing 

scanning since CT slices are arbitrary snapshots acquired without 

any time-information of the moving tumor. These respiratory induced 

artifacts result in uncertainties in the target definition and therefore an additional 

margin is necessary to prevent under-dosage of the tumor. However, 

large uncertainties need large margins (yielding large PTV’s), which limits 

dose to the tumor and may increase the dose to healthy tissue and organsat-risk.Currently, 

4D respiration-correlated CT imaging techniques to obtain 

a scan without these respiration-induced artifacts have been developed and 

potentially can help to reduce the uncertainty. However, sensible use of a 4D 

CT scans in treatment planning is essential. The target volume (TV)-to-PTV 

uncertainty margins can be calculated using the population-based statistics 

margin recipe M=2.5Σ+0.7σ, incorporating systematic (Σ) and random (σ) 

uncertainties. Uncertainties due to inter-fractional setup errors, baseline variation 

(changes in mean tumor position) and patient specific respiration need 

to be included. However, the contributions of these uncertainties differ for 

different TV definition approaches (ITV, Gated RT and Mid-ventilation).A simulation 

of 45 patients was performed to compute the uncertainty margins and 

treatment volumes for different TV approaches. It showed that on average the 

ITV method resulted in a significantly increased irradiated volume. The TV 

for the gating and mid-ventilation methods resulted in an approximately equal 

PTV reduction compared to the TV for free-breathing CT. To show the feasibility 

of the mid-ventilation approach, finally, a verification of the dose coverage 

of the mid-ventilation approach is performed by a full 4D dose accumulation 

over the respiratory cycle for ten patients. This verification showed that good 

dose coverage will be obtained, even when the tumor motion is larger than 3 

cm.In conclusion, using a simple mid-ventilation approach results in an equal 

PTV size as gated radiotherapy with an adequate dose-coverage. Therefore 

gated radiotherapy can be considered redundant for lung cancer patients. 

393 speaker 

CLINICAL CASE: BREAST - FOCUS ON THE BENEFIT OF GATED 

DELIVERY IN INSPIRATION OR DEEP INSPIRATION 

A. Pedersen 1 

1 THE FINSEN CENTER - RIGSHOSPITALET, Radiation Oncology, Copen- 

hagen, Denmark 

Breast radiotherapy has evolved over the past century to provide the most 

contemporary technique using a non-divergent co-planar tangential field 

beam. Such technique is challenged with the geometry of often large breast 

size or internal mammary lymph node co-irradiation with mediolateral target 

extensions bending concavely around risk organs, and with respiratory motion 

of target and risk organs, and with fluctuation of lung tissue density. In 

the adjuvant setting the majority of patients are over treated, but all are at 

risk of cardiopulmonary side-effects This concern regards particularly heart 

and coronary arteries in left-sided cases, potentially offsetting the survival 

benefit, thus emphasizing the need for further reduction of the low risk of cardiac 

side effects. The aim of respiratory gating in breast radiotherapy is to 

implement a comprehensible technique applicable to a large patient group, 

and to reduce radiation doses to risk organs, without compromising doses 

to target structures. Inspiration implies posteroinferior displacement of the 

heart, consistently indicating that only a slight change in heart position appreciably 

impacts the volume in field of left-sided cases. Furthermore, lung 

inflation significantly reduces volume of lung in the high dose region irrespective 

of side. In contrast to intensity modulation, no change in target or contralateral 

organ doses are experienced. Free breathing gating compares well 

with deep inspiration breath-hold in terms of dosimetric risk organ sparing. 

Breast patients show good breathing compliance, why audio coached enhanced 

free breathing gating further improves the spatial organ separation 

and thereby favourises the dosimetric benefits for breast conservation as well 

as mastectomy cases. For routine gated patients the calculated normal tissue 

complication probabilities compare well with the predicted values from 

pre-clinical computer tomography studies.At Rigshospitalet, Denmark, gated 

breast radiotherapy has been in routine use since 2004 as standard of care 

for left-sided cases requiring internal mammary lymph node co-irradiation, 

with more than 350 patients treated so far. Less than 10% of patients eligible 

are excluded from this technique, primarily due to non-compliance. Except 

from individualised patient respiration training, treatment planning as well as 

slot times are resource equal to non-gated treatments. 

394 speaker 

CHALLENGES IN ONLINE IMAGE GUIDED RESPIRATORY MAN- 

AGEMENT FOR LIVER TUMORS 

K. Brock 1 


Image guided radiotherapy (IGRT) combined with respiratory management 

techniques for liver cancer has the potential to improve tumor response and 

reduce complications by decreasing treatment margins while ensuring accurate 

delivery of the intended dose. IGRT for liver cancer, however, remains 

challenging due to lack of inherent contrast between the liver and the tumor, 

making direct targeting of the tumor difficult, if not impossible. Respiratory 

management techniques, such as gating and breath hold, require IGRT at 

delivery to account for day to day changes in baseline breathing position and 

breathing motion. Recent research has investigated the application of these 

combined techniques.Research has shown the ability to safely escalate the 

dose to both primary and metastatic liver tumors using respiratory management 

techniques. These techniques include allowing the patient to breath 

normally and modifying the treatment beam (i.e. gating and tracking) and 

modifying the patients breathing while delivering a standard treatment beam 

(i.e. breath hold and abdominal compression). Techniques such as these are 

warranted when respiratory motion exceeds 5 mm. Uncertainties have been 

shown to exist when using these techniques, such as variations between external 

surrogates which monitor breathing and variations in the breath hold 

position relative to boney anatomy. Advances in online image guidance technology 

enable verification and validation of these techniques prior to treatment 

and throughout the treatment delivery.Online image guidance for the 

liver is challenging. The vast majority of tumors in the liver are only visible 

under optimally timed contrast enhancement. Changes in the shape as well 

as position of the liver leads to some uncertainty in the use of rigid registration 

to map the tumor, identified on the diagnostic quality pre-treatment 

imaging, onto the online IGRT images. Research into deformable registration 

techniques is challenged by time constraints and the in-room imaging 

(e.g. 2D data and 3D/4D data with less contrast). Recent advancements has 

allowed ’4D’ and breath hold imaging technology to extend into the in-room 

imaging setting, allowing for improved identification of the liver boundary.This 

presentation will focus on the need for the integration of IGRT with respiratory 

management techniques, methods to overcome the limited visualization 

of the tumor in IGRT of the liver through improved integration of pre-treatment 

images, and the potential for gating and breath hold techniques in liver cancer 

treatment. 

Stereotatic body irradiation 

395 speaker 

THE DEVELOPMENT OF STEREOTACTIC BODY RADIOTHERAPY 

I. Lax 1 

1 KAROLINSKA UNIVERSITY HOSPITAL, Hospital Physics, Stockholm, 

Sweden 

Based on the experience from intracranial stereotactic radiosurgery/radiotherapy, 

and considering the very potent volume effect 

experienced in radiotherapy, localized hypofractionated stereotactic radiotherapy 

to extremely high biological target doses of macroscopic tumors in 

the lungs and liver was initiated the first years of the 1990s, to which the 

acronym SBRT later was established. The initial characteristics of SBRT 

were, apart from the stereotactic methodology, a planned heterogeneous 

dose distribution within PTV for an improved therapeutic ratio, tomographic 

geometrical verification of the tumor position in the stereotactic coordinate 

system, hypofractionation and the use of methods for reduction of breathing 

motions of the target. From about the mid 1990s the fractionation scheme 

with generally three to five fractions have been used, though less than three 

fractions are used to some extent for very small tumors. Initial promising 

clinical results of SBRT and general availability of technology has rapidly 

disseminated of the treatment philosophy as well as stimulated scientific 

activities in the field. Results from clinical trials of SBRT have established 

tumor effects and toxicity, confirming initial experience, especially for early 

stage lung cancer. Broad activities in SBRT have in later years focused on 

technical and methodological issues of optimized dose delivery, with much 

attention to questions related to targets moving with the respiration, while 

basic questions in this emerging field are of radiobiological nature, in terms 

of organ and tumor response to unconventional spatial and temporal dose 

distributions. Response patterns established from conventional radiotherapy, 

of typical host organs in SBRT, such as the lung, seems to be quite different 

in SBRT. Increasing considerations of the fine-structure of the host organs 

and targets will likely be of increasing importance to understand the response 

of SBRT. 

396 speaker 

BALANCING TUMOR EFFECT AND NORMAL TISSUE EFFECT IN 

STEREOTACTIC BODY RADIOTHERAPY (SBRT) 

W. Tomé 1 , M. Mehta 2 

1 UNIVERSITY OF WISCONSIN SCHOOL OF MEDICINE AND PUBLIC HEALTH, 

Department of Human Oncology and Medical Physics, Madison, USA 

2 UNIVERSITY OF WISCONSIN SCHOOL OF MEDICINE AND PUBLIC HEALTH, 

Human Oncology, Madison, USA 

Objective: A model that balances expected tumor and normal tissue effect 

for various SBRT schedules is discussed. 

Methods and Materials: Because SBRT uses a small number of fractions 

delivered in less than two weeks, accelerated repopulation is not believed to


be a significant concern; a schedule that delivers a minimal peripheral tumor 

normalized total dose (NTD) ≥ 84 Gy10 is projected to achieve ≥ 80% progression 

free survival at 30 months. In order to balance expected tumor and 

normal tissue effect, the NTDmean to the residual healthy lung (both lungs 

PTV) has to be kept below 19Gy3 (dose at which the risk of pneumonitis ≤ 

20%), while delivering a minimal peripheral tumor NTD10 ≥ 84 Gy10 to the 

PTV. 

Results: Our modeling shows that the selection of a schedule which allows 

one to balance tumor and normal tissue effect depends on the ratio of Prescription 

Isodose Volume (PIV) to residual lung volume. This ratio is directly 

correlated with the NTDmean received by the residual lung for a fixed minimal 

peripheral late local damage NTD3 MP around the high dose volume. 

Conclusion: In order to choose the schedule with the highest 30-month progression 

free survival, one needs to minimize the PIV as far as possible 

without compromising PTV coverage. This indicates the need to incorporate 

advanced treatment planning techniques, 4D imaging, and volumetric 

image guided treatment delivery techniques into the SBRT process. Inverse 

planning can be used to reduce the PIV by conforming dose more closely to 

the PTV. 4D imaging can be used to better define the PTV. Volumetric image 

guided treatment delivery can reduce the systematic and random setup errors 

down to the level of imaging uncertainty, and therefore allows one to reduce 

margins to only take account of breathing motion of the GTV, the extent of 

microscopic disease, and the imaging uncertainty yielding a smaller PTV. To 

test this model we are currently conducting a randomized clinical trial. 

397 speaker 

SEVERE HYPOFRACTIONATION AND INTRA-TUMOUR DOSE 

HETEROGENEITY IN STEREOTACTIC BODY RADIOTHERAPY: AN 

ANSWER TO TUMOUR HYPOXIA? 

R. Ruggieri 1 

1 ISTITUTO SCIENTIFICO ROMAGNOLO PER LO STUDIO E LA CURA DEI 

TUMORI, Medical Physics, Meldola (FC), Italy 

A rationale for the severe hypofractionation adopted in stereotactic body radiotherapy 

(SBRT) has been generally based on the small size of the highdose 

volumes in the adjacent parallel organs at risk (e.g., lungs or liver). Such 

an approach, however, does not take into account the effect of the intrinsic tumour 

dose heterogeneity of SBRT. By dose prescription to about 70% of the 

dose-normalization point, SBRT techniques ensure, in fact, a tumour dose 

delivery which is well-approximated by a simultaneous dose-boosting (sdb) 

strategy to about 50% of the tumour volume at a dose-boost ratio (dbr) equal 

to about 1.3.Such intrinsic tumour dose heterogeneity might impact on the 

radioresistant hypoxic tumour clonogens probably present during SBRT as a 

result of the inefficiency of reoxygenation when a small number of fractions 

are employed. However, a simple model assuming an Oxygen Enhancement 

Ratio (OER) around 3 for all the hypoxic clonogens would require a dbr 

greater than 1.3. Further, the absence in SBRT of an explicit hypoxia targeting 

strategy (’blind’ sdb) ought to be considered.A more complex model 

will thus be presented, where the chronic and acute components of tumour 

hypoxia are separately analyzed and different estimates for the OER from recent 

literature, which try to include the effects of in vivo prolonged hypoxia, 

are considered.According to this model, an appreciable gain in tumour control 

probability (TCP) is predicted for SBRT ’blind’ sdb compared to homogeneous 

tumour irradiation. Further, the specific targeting of chronic hypoxia (e.g. 

by the optimized use of certain PET-tracers) might be a promising strategy 

to further increase the TCP. Finally, with reference to iso-toxicity schedules 

for variable number of fractions, n, computed on individual NSCLC patients 

which were planned for homogeneous and ’blind’ sdb tumour irradiations, it 

will be shown that a Poissonian-LQ TCP model which assumes no tumour hypoxia 

too easily justifies the use of severe hypofractionation, even for large tumour 

volumes. By contrast, the inclusion of tumour hypoxia strongly reduces 

the appeal of severe hypofractionation, unless ’blind’ sdb is concurrently performed. 

Therefore, intrinsic tumour dose heterogeneity might complement 

the high level of dose-sparing to the adjacent normal tissues in a rationale for 

the reported effectiveness of severely hypofractionated SBRT. 

398 speaker 

4-DIMENSIONAL STEREOTACTIC RADIOTHERAPY WITH REAL- 

TIME TUMOUR MOTION TRACKING US 

J. Nuyttens 1 



The CyberKnife is a frameless, image-guided radiotherapy system involving 

a 6-MV linear accelerator mounted on a robotic arm possessing six degrees 

of freedom. The imaging system uses 2 diagnostic X-ray sources mounted to 

the ceiling and paired with amorphous silicon detectors to acquire live, digital 

radiographic images of the patient. The Synchrony system requires the insertion 

of markers in or near the tumour, which are used to define the tumour’s 

position. The motion of light emitting diodes placed on the patient’s torso is 

continuously registered by a camera array. The system makes a correspon- 

S 131 

dence model between the movement of the internal markers and the LEDs, 

based on 6-8 X-ray images taken at the start of the treatment. This model 

enables the linear accelerator to continuously track the motion of the markers 

via the motion of the LEDs, thereby adjusting automatically the position of 

the beam relative to the moving target. The correspondence model is continuously 

updated throughout the treatment by the regular acquisition of X-ray 

images. At the Erasmus MC, this robotic stereotactic radiotherapy system 

is used since March 2005 to irradiate early stage lung tumors and solitary 

metastasis in the lung in medically inoperable patients or in patients who 

refuse surgery, and until now more than 150 patients are treated. Different 

methods of fiducial placement are developed and will be discussed as well as 

the technique. Peripheral tumors were treated with a total dose of 60 Gy (20 

Gy/fr), or with a total dose of 45 Gy (15 Gy/fr). Central tumors were treated 

with 6*8 Gy , 5*9 Gy or 5*10 Gy, depending on the proximity of the organs 

at risk like trachea and oesophagus. The PTV equals the GTV + 5 mm. The 

dose to the PTV was prescribed to the 70-85% isodose line. The response 

was evaluated according to the RECIST criteria with a CT 8 weeks after the 

last treatment and routinely thereafter. The early results of the first 100 tumors 

in 77 patients with 77 early stage lung cancer tumors and 14 patients 

with 23 solitary metastases are promising and show that four-dimensional tumor 

tracking for these patients resulted in a 2 years local control of 94% with 

doses of 60 Gy in 3 fractions. Central tumors or tumors treated with a lower 

dose had a lower local control. Further research is needed to establish the 

dose for central tumors. 

Management of gynaecological tumours 

399 speaker 

ADVANCED PRACTICE IN BRACHYTHERAPY: AN EXAMPLE OF 

RADIOGRAPHER ROLE EXTENSION, AS PART OF THE FOUR TIER 

STRUCTURE IN THE UK 

E. Armstrong 1 

1 UNIVERSITY COLLEGE HOSPITAL, Radiotherapy, London, United Kingdom 

The NHS Plan released in 2000 aimed to modernise the NHS and improve 

services. It specifically wanted to create a more patient-centred service with 

reduced waiting times and increased access to treatment. To facilitate these 

goals it was aimed to make full use of health professionals’ skills by extending 

professional boundaries. Since 2000 advanced practice has impacted greatly 

on health care in the United Kingdom (UK) with the allied health professionals 

(such as physiotherapists, nurses and radiographers) extending their responsibilities 

into previously clinician lead roles. In radiotherapy advancing 

treatment techniques are putting increasing demands on oncologists’ time. 

This has encouraged new ways of working by utilising one of the greatest 

resources it possesses: the workforce. Now roles are to be defined by skill 

and competency, not profession. The four-tier structure facilitates extended 

roles by the introduction of advanced practitioners and ultimately consultant 

practitioners. In addition are the roles of practitioner (registered radiographers), 

and assistant practitioner (those working under direction and supervision). 

Advanced practitioners develop skills and responsibilities beyond that 

required at professional registration. At University College Hospital (UCH) in 

London radiographers have taken part in post-registration Masters Degree 

training in: intravenous contrast administration, breast simulation, and gynaecological 

brachytherapy. Vaginal vault brachytherapy insertions provide 

an ideal opportunity for radiographer advanced practice as it allows a specific 

area of expert practice to be gained. At UCH the service has been radiographer 

led for 18 months, and is proving beneficial for all involved. The clinical 

need behind the service redesign was to offer an efficient service with an 

optimum distribution of skills, thus providing a cost effective service. The clinician 

led service was not flexible and often resulted in keeping patients waiting. 

These issues are no longer a problem; ladies attending for brachytherapy 

are offered flexible appointments and are seen with minimal delay. Clinicians’ 

time has been released which can be used in other areas of patient care, 

for example exploring the use of 3D planning for intra-uterine brachytherapy 

insertions. The professional development of radiographers can also have 

a positive impact on their job satisfaction and therefore on recruitment and 

retention. Radiographer role extension should not however be undertaken 

without a robust teaching process. This involves assessment through an 

accredited teaching establishment and in-house teaching and training from 

clinical staff. In addition financial support (to cover fees) and staffing support 

(to facilitate study leave) must be provided.To conclude a radiographer 

led brachytherapy service (for vaginal vault insertions) has worked well for 

UCH, benefiting patient, clinician and radiographer. However, considerable 

logistical planning was required prior to implementation to achieve a smooth 

handover.


400 speaker 

GYNAECOLOGICAL CANCER TREATMENT AND SEXUAL DYS- 

FUNCTION 

K. Bergmark 1 

1 KAROLINSKA INSTITUTET, Department of Gynaecological Oncology, 


After cervical carcinoma, sexual dysfunction is the symptom that distresses 

the greatest proportion of women. The majority of cervical cancer survivors 

are young or middle-aged women who will live many years with their 

treatment-induced sequelae. The impact on sexual function after treatment 

of other forms of gynaecological cancer is not as well studied, but it is shown 

that also many women with endometrial, ovarian and especially vulvar cancer 

have major sexual dysfunction. The origin can be physical, psycological 

and social. The disease- and treatment-induced morbidity can affect the 

sexual function and libido, and thus affect the prerequisites for the sex-life. 

Treatment-induced changes of the mucous membranes and supporting tissues, 

nerve- and vascular damage and hormonal factors are all involved, 

after radiotherapy, surgery as well as after chemotherapy. The women report 

insufficient lubrication, vaginal shortness and inelasticity, and dyspareunia. 

Preventive issues, including nerve-preserving surgery, interventions and rehabilitation 

may diminish the development of sexual dysfunction. Information 

about sexual dysfunction is often the most important issue when patients are 

asked about what side-effects they want more information about. By giving 

the patient and her partner the opportunity to discuss sexual issues early in 

the course of treatment, the impact of disease and treatment on the sexual 

function can be less severe. Background factors, both physical and psychological, 

and preventive and interventive actions will be discussed. 

401 speaker 

THE COMPLEXITIES OF MANAGING SEXUAL HEALTH FOLLOWING 

A DIAGNOSIS OF A GYNAECOLOGICAL CANCER 

L. Punt 1 

1 ADDENBROOKE’S HOSPITAL, Oncology, Box 193, Cambridge, United 

Kingdom 

"As advances in prevention, detection and management of cancer increases 

the likelihood of long-term survival, the ethos of cancer treatment now lies not 

only in ’survival’, but quality survival."(1) 

Introduction: With advancing techniques in treatment delivery survival rates 

in the field of gynaecological oncology have been steadily rising. In cervix 

cancer alone survival across all stages is relatively high with an overall 5year 

survival rate of 64% (2) 

This demonstrates that not only are more women surviving following radical 

treatment, but also a significant number of women are living longer with the 

consequences of their disease and it’s treatment. The impact of long term 

side effects on quality of life issues therefore play a more significant role in 

the quality outcome measures of treatment. 

Discussion. 

To consider the multi-faceted issues contributing to sexual dysfunction, following 

a diagnosis for and treatment of a gynaecological cancer. 

To identify the pivotal position health care professionals are in to positively 

influence patient outcomes by legitimising sexual health. 

To highlight those issues that impede provision of support and information. 

To summarise how the complexities of sexual health management will be best 

addressed within a multi-professional team providing a truly holistic, patient 

centred approach. 

To identify areas of research needed to develop National and International 

strategies for the management of sexual dysfunction. 

(1) Bahadur G. (2000) Fertility issues for cancer patients. Molecular and cellular 

endocrinology. Aug;169:117-122 

(2) Coleman M, Rachet B, Woods L, et al. (2004) Trends and socio-economic 

inequalities in cancer survival in England and Wales up to 2001. British Jornal 

for Cancer. 9th March 1367-1373 

Advances in the management of malignant glioma 

402 speaker 

THE POTENTIAL OF MODERN IMAGING TECHNIQUES IN DEFIN- 

ING THE RADIOTHERAPY TARGET V 

A. L. Grosu 1 

1 UNIVERSITY FREIBURG, Radiation Oncology, Freiburg, Germany 

For many tumour types, radiation therapy is considered an efficient method 

to ’kill tumour cells’ and the ’target and destroy’ principle is fundamental to its 

efficacy. Focusing the irradiation dose on the tumour and sparing the normal 

tissue are the most important goals of radiation therapy technique. This al- 

lows dose escalation for tumour tissue and dose reduction for normal tissue to 

achieve greater tumour control and a lower rate of side effects. As such, technological 

developments of the last decades have focused on the improvement 

of hardware and software systems able to deliver irradiation with a high geometrical 

accuracy. The radiation treatment plan is traditionally based on the 

data of computer tomography (CT) and magnetic resonance imaging (MRI). 

The enormous advantage of these investigations is the non-invasive, highly 

accurate anatomical 3-D visualisation. Fundamental concepts in the definition 

of target volume were formulated based on the results of these investigations, 

such as gross tumour volume (GTV), clinical target volume (CTV), 

and planning target volume (PTV). GTV defines the macroscopic tumour volume, 

as defined by radiology or clinical investigation, CTV encompasses the 

GTV plus the microscopic tumour infiltration, and the PTV includes the GTV 

and CTV plus a small margin, which takes into account possible inaccuracies 

introduced by patient/organ motion during radiation delivery. Huge clinical 

experience has accumulated over the years using these investigations, but 

time and experience has shown not only the advantages, but also the limits 

of CT and MRI or of so-called ’anatomical imaging’. Tumour visualization 

using these techniques is based on variation of tissue density (CT) or intensity 

(MRI), on volume effects and on contrast enhancement. However, these 

are not necessarily specific tumour characteristics. Similar changes may also 

be seen in non-tumour tissue due to pathological conditions, such as inflammation, 

or after therapy (surgery, radiotherapy or chemotherapy). Therefore, 

anatomical imaging could have limits in the presentation of tumour anatomy 

(tumour extension), when tumour and normal tissue have similar density (intensity) 

or similar properties concerning contrast enhancement. In recent 

years, new methods of tumour visualization have advanced the domain of 

medical imaging. Techniques like positron emission tomography (PET), single 

photon emission computed tomography (SPECT) and magnetic resonance 

spectroscopy (MRS) enable visualization of tumour biology, giving additional 

information about metabolism, physiology and molecular biology of tumour 

tissue. This new class of images, showing specific biological events, complements 

the anatomical information of traditional radiological techniques. IMRT 

combined with a treatment plan based on biological imaging could be used 

for future biological individualization of radiation therapy. The first rationale 

for using biological imaging in TVD is the higher sensitivity and specificity of 

these investigations for tumour tissue, in comparison to CT and MRI. For example, 

for PET this was demonstrated in many studies, which compared the 

results of PET with the results of the radiological investigations and histology. 

The hypothesis tested in these studies, was that using PET in addition 

to CT and/or MRI, enables GTV to be delineated with a higher accuracy. The 

ideal PET tracer in this situation should be taken up homogenously from all 

the cells of the whole tumour and the intensity of the PET uptake should be 

directly proportional to the density of tumour cells. The second rationale for 

integrating biological imaging in the process of radiation treatment planning is 

the ability of PET to visualize biological pathways, which can be targeted by 

radiation therapy. The imaging of hypoxia, angiogenesis, proliferation, apoptosis 

etc. leads to the identification of different areas of an inhomogeneous 

tumour mass, areas of which can be individually targeted. For example, hypoxic 

areas can be treated with higher radiation doses than non-hypoxic areas. 

The goal of this presentation is to summarize data of current literature 

concerning the use of biological imaging for TVD in the process of radiation 

treatment planning. 

403 speaker 

COMBINED CHEMO-RADIOTHERAPY: ADVANTAGES AND DISAD- 

VANTAGES OF NOVEL TECHNOLOGY AND TREATMENT DELIVERY 

D. C. Weber 1 , F. Villa 2 

1 GENEVA UNIVERSITY HOSPITAL, Radiation Oncology, Geneva, Switzerland 

2 ICO, BADALONA, Radiation Oncology, Barcelona, Spain 

Radiation therapy, with or without concomitant chemotherapy, for high-grade 

glioma is effective with an undisputedly demonstrated improvement in patient’s 

outcome, compared with supportive care or chemotherapy alone in 

phase III trials. RT results usually in a remarkable, albeit temporary, improvement 

of patient’s performance status and neuro-cognitive function. Unfortunately, 

the benefit of conventional RT does not extend to cure for the vast 

majority of patients. As such, glioblastoma glioma patient have a poor prognosis, 

with a reported 5-year overall survival of 60 Gy) radiation dose delivery. The reason of 

treatment failure may be essentially two folds. First, radiation delivery may 

be targeting clinical target volumes that are not optimally defined. With current 

non-metabolic imaging technology, using radio-labelled amino acids or 

misonidazole analogues, we can indeed deliver multi-dimensional conformal 

RT with a high degree of geometrical precision but with somewhat suboptimal 

biological conformity. Alternatively, functional imaging may enable radiation 

oncologists to better define non target structures, as to optimally spare these


regions. More specifically, using Tomotherapy for brain tumour patients, it is 

possible to treat metastases, whilst sparing the hippocampus[1]. Other studies 

have shown that using functional MRI and IMRT planning will diminish the 

mean dose to the contralateral and ipsilateral primary motor cortex. The first 

talk of this symposium will focus on the issue of target definition for high-grade 

glioma. Second, the radioresistance of high-grade glioma may be too important; 

60 Gy delivered to the target volume may be too conservative a dose to 

optimally control this tumour. Mathematical modelling of survival of glioblastoma 

patients, using Monte Carlo simulation, suggests that the patient’s survivorship 

would be increased > 2.5 fold with a dose increment of 60 to 74 

Gy. To deliver this radiation dose level, non-conventional RT, not limited to but 

including helical Tomotherapy, hadrons’ beam therapy or intensity modulated 

RT (IMRT), the latter two with imaged-guided dose delivery, may be required. 

Dose comparative studies have suggested that Tomotherapy and IMRT techniques 

are equieffective in terms of tumour coverage and to adherence to the 

stringent clinical dose constraints. Moreover, these aforementioned delivery 

techniques have differential performance ratio (i.e. newly increase performance/consequential 

performance decrease), as these delivery modalities 

have been precisely honed on a delivery aspect. As a result, enhancement of 

one aspect of the machine performance is usually accompanied by a diminution 

of an other[2]. The inception of non-conventional RT brought with it great 

excitement in Neuro-oncolgy, as the radiation dose conformality available with 

non-conventional RT is unparalleled. In this presentation, the pros and cons 

of non-conventional RT will be described. In essence, the advantages of 

these techniques are: 1) the ability for the radiation oncologist to paint (i.e. 

shape) dose to the organs at risk abutting the target volume, while fully dosing 

the tumour and regions of microscopic spread; 2) to decrease the volume 

of non-target structures receiving high-dose radiation; 3) to implement into a 

clinical setting image guidance and adaptive dose guidance. CT imaging for 

patient setup verification allows one to correct for interfraction setup errors; 

and 4) to deliver a simultaneous integrated boost (SIB) to overcome radioresistance. 

Regarding the latter, it is a fundamental principle of radiobiology 

that, all things being equal, the probability of controlling a tumour rises as the 

radiation dose is increased. Delivering IMRT for glioblastoma seems equitoxic 

to conventional RT with an IMRT boost. Although a Japanese group has 

shown an increase of PFS and OS for malignant glioma patients treated with 

hypofractionated IMRT using SIB compared with non-IMRT, two US group did 

not demonstrate any survival advantage (median OS, 9 months) in patients 

treated with standard fractionation IMRT. The disadvantages of non conventional 

RT may be however clinically relevant and includes: 1) increase of 

radiation-induced necrosis in regions treated with inhomogeneous dose after 

high dose RT or chemo-RT; 2) increase of neuro-cognitive dysfunction as 

a result of white matter alterations, consequently to the increase of integral 

dose delivered to the brain. Studies have shown that demyelination and mild 

structural degradation of axonal fibers occur in normal-appearing white matter 

after RT and that this process is dose-dependant; 3) RT associated costs may 

be an issue depending on health system and re-imbursement policy. These 

costs may be large but could substantially decrease with learning effects: a 

French study has shown that the treatment direct costs were halved in centers 

with a previous experience of IMRT, when compared to those with no IMRT 

experience. To conclude a radiographer led brachytherapy service (for vaginal 

vault insertions) has worked well for UCH, benefiting patient, clinician and 

radiographer. However, considerable logistical planning was required prior to 

implementation to achieve a smooth handover. 

404 speaker 

COMBINING VASCULAR AGENTS AND RADIATION - COMING TO 

THE CLINIC 

A. Dicker 1 

1 THOMAS JEFFERSON UNIVERSITY, Department of Radiation Oncology, 

Philadelphia, USA 

Glioblastoma multiforme (GBM) tumors are the most common and aggressive 

form of primary brain tumors in adults. Recent clinical studies indicate that 

adding the DNA damaging agent, temozolamide (TMZ), to radiotherapy (RT) 

increases survival in GBM and that the addition of EGFR inhibitors provide 

benefit for GBM patients with specific tumor genotypes. In this connection, 

30-40% of all GBMs contain amplification of the EGFR gene or overexpression 

of EGFR or a mutant variant, EGFRvIII; these genetic alterations are 

thought to confers radio- and chemoresistance on tumor cells. The mechanism/s 

whereby EGFR inhibition provide benefit for GBM patients is not 

clearly understood. It is known that EGFR inhibition prevents downstream 

signaling to MAPK and PI3K/Akt and thereby regulates cell cycle progression, 

proliferation, apoptosis and angiogenesis. Recent data also link EGFR 

family-initiated pathways to DNA damage and DNA repair. Poly-ADP-ribose 

polymerase (PARP-1) is a nuclear enzyme that is a component of the DNA 

base excision repair system. Its catalytic activity is stimulated by DNA strand 

breaks arising from cancer cytotoxic therapies such as chemo-radiotherapy 

and its activity and/or expression has been found to be elevated in human 

cancer. PARP-1 activation can also occur through DNA-independent mechanisms 

through a MAPK signaling cascade. Therefore PARP-1 activation may 

be regulated by upstream EGFR-initiated pathways. The presentation will discuss 

approaches that are being taken at the preclinical and clinical levels to 

build on rational approaches to the combination of targeted agents (antiangio- 

S 133 

genics, PARP inhibitors, etc) with with chemo-radiation and how translational 

research will bring laboratory bench research to the bedside and back. 

IMRT for breast cancer: a new standard? 

405 speaker 

WHEN TO CONSIDER IMRT FOR BREAST CANCER? 

T. Juhler-Nøttrup 1 , F. Kjær-Kristoffersen 1 , A. N. Pedersen 1 , S. Korreman 1 

1 THE FINSEN CENTER - RIGSHOSPITALET, Department of Radiation 


Breast irradiation takes up approximately half of the numbers of patients 

treated in our department of radiotherapy, calling for standard methods or 

class solutions. Five years ago, most centres used 2D treatment planning 

for breast cancer radiotherapy, but today the question is if IMRT should be 

the standard planning method. Numerous publications have evaluated the 

potentials of IMRT suggesting improved dose homogeneity, reduced toxicity 

and efficacy, although not all patients will benefit from IMRT. We only use 

IMRT as our standard for very few patients. The three main reasons for this 

are; IMRT is associated with large patient volumes receiving a low dose, it 

is not possible to predict which patients will gain form IMRT, and IMRT is 

more sensitive to target motion than conventional 3D CRT. Radiotherapy for 

breast cancer is complicated with a challenging target geometry that bends 

concavely around the organs at risk. The long term toxicity of the treatment 

includes excess mortality which is important for this group of patients who 

are most likely to be cured. This challenge calls for optimal target coverage 

and precise evaluation and minimisation of dose to organs at risk. We use 

to the national guidelines from the Danish Breast Cancer Cooperative Group 

for target definition and dose constrains to organs at risk. With respect to 

these guidelines most patients can be treated with conventional 3D CRT. For 

patients with stage II left sided breast cancer (both lumpectomy and mastectomy), 

we include parasternal node irradiation. In these cases we have used 

gating with audio coaching as the standard treatment since 2004 to minimise 

dose to organs at risk. 3D CRT and the use of gating for the mentioned left 

sided cases, together with careful evaluation of the target definition, produce 

sufficient plans for 99% of our breast cancer treatments. For the remaining 

patients we have used IMRT. In all we have treated 29 breast cancer patients, 

of more than 900 patients treated with IMRT the last 7 years at Rigshospitalet. 

For more than 60% of the breast cases, IMRT was combined with gating and 

8 patients had bilateral cancer. The experiences we gained from gating, controlling 

the extend of the respiratory motion, and the on-line and off-line verification 

and correction of this motion, have been valuable introducing IMRT. 

With IMRT we want to keep the respiratory motion of the target as low as 

possible, to rely on the calculated dose distribution. We use vacuum bags to 

immobilise the patient and this immobilisation reduces the anterior posterior 

motion of the breast during breathing with 50% compared to patients without 

immobilisation. The spontaneous anterior posterior breathing motion is reduced 

to a mean value of 2.5 mm after immobilisation. Knowing the motion to 

be minimal in one direction, it is possible to optimise the beam configuration 

and the leaf motion accordingly. 

406 speaker 

IDENTIFYING SENSIBLE PLANNING SOLUTIONS 

C. Hurkmans 1 

1 CATHARINA HOSPITAL, Radiotherapy, Eindhoven, Netherlands 

The use of IMRT and other advanced techniques is rapidly increasing, also for 

breast cancer patients. Although in general, local control and overall survival 

for breast cancer is high and radiotherapy complications limited compared to 

other cancers, there are still significant improvements possible. Besides a 

further increase in local control, a further reduction of early and late complications 

is of importance and will improve the quality of life. This session will 

mainly focus on irradiation of the breast or thorax alone (without locoregional 

lymph node areas), as these local treatments benefit most from the introduction 

of IMRT. The delineation of the target volumes, e.g. the breast tissue 

and the boost clinical target volume is a difficult task and cooperative group 

guidelines for these delineations will be discussed. Also, defining sensible 

CTV-PTV margins is challenging. In order to reduce complications, the main 

organs at risk (i.e., the breast, lungs, ribs and heart) need to be taken into 

account. Dose-volume criteria for organs at risk will be discussed and their 

validity. Thereafter, examples of IMRT solutions for breast or thorax irradiation 

will be presented with or without an additional boost. The concepts of sequential 

and simultaneous integrated boosts and their respective advantages and 

disadvantages will be highlighted. The use of breathhold techniques will be 

discussed in the context of reducing cardiac morbidity.


407 speaker 

3-D POSITION VERIFICATION OF WHOLE BREAST IRRADIATION; 

IS IT WORTHWILE? 

M. Mast 1 , J. Egmond van 1 , J. Santvoort van 1 , H. Struikmans 1 

1 MEDICAL CENTRE HAAGLANDEN, Radiotherapy, The Hague, Netherlands 

Breast cancer is the most common malignant disease in the Western Europe. 

In an average radiotherapy department, 20-30% of the cancer patients 

are treated for breast cancer. Whole breast irradiation should be applied in 

such a way that the target volume is covered adequately and heart and lungs 

are spared as much as possible. This is of such vital importance because 

of the reported risks of increased serious cardiac damage (due to the use 

of chemotherapy, biologicals and radiotherapy) and lung cancer (associated 

with smoking). The use of a planning CT scan enables the delineation of the 

CTV as well as organs at risk (heart and lungs) and enables the evaluation 

of the 3D dose distribution. The use of a planning CT scan, however, is not 

a standard procedure for patients with breast cancer. The use of modern 

techniques (IMRT and SIB) is increasingly used in departments of Radiation 

Oncology all over Western Europe. An essential part of the quality of the 

treatment is position verification. The method of visual verification immediately 

before treatment is commonly used to confirm that the light field covers 

the entire breast. In our opinion the adjustment of the patient position is of 

great importance because of the close relation between the treatment fields 

and the organs at risk. To visualise the position of the patient during the 

course of radiotherapy, an Electronic Portal Imaging Device (EPID) or a Cone 

Beam CT (CBCT) can be used. Both techniques can be said to have several 

pros and cons. Using EPID has the advantage that it takes little time, 

and as its disadvantages that the images can be hard to interpret, and that 

extra doses (MV) are obligatory. Using CBCT has the advantage of giving 

information on soft issue (this implicates CTV); however it has the disadvantages 

of costing extra time because of the matching procedures and the fact 

that extra doses (KV) are obligatory. Gold markers can be used to visualise 

the lumpectomy cavity in the breast. But one has to be aware both of the 

interobserver variability’s in delineating the CTV boost and of the change of 

CTV boost volume variation during the course of radiotherapy. In conclusion, 

introducing IMRT and SIB techniques for breast cancer patients is important. 

However, position verification is just as important in order to adjust the patient 

position. All of this will be discussed at during the presentation. 

ESMO/ESSO/ESTRO - State of the art in the management 

of rectal cancer II 

408 speaker 

LOCAL EXCISION OF RECTAL CANCER - SELECTION AND 

RESULTS 

I. Taylor 1 

1 UNIVERSITY COLLEGE LONDON, London, United Kingdom 

There is increasing interest in local excision for early rectal cancer (ERC). 

ERC is defined as invasive adenocarcinoma spreading into but not beyond 

the submucosa (T1 tumour). Accurate pre-operative diagnosis is essential 

and several techniques are available including endorectal ultrasonography 

and MRI. In appropriately selected patients, T1 tumours can be cured by local 

excision. Endoscopy polypectomy is appropriate for polypoid tumours on 

a stalk. If the tumour is sessile, endoscopic excision by this method is less 

satisfactory. For sessile lesions not suitable for polypectomy, other surgical 

options are available." Extensive polypectomy with endoscopic mucosal resectionThese 

techniques for sessile tumours are feasible but it may be more 

difficult to ensure complete excision." Per-anal excisionIf the lesion is within 

10cm of the anus per-anal excision with appropriate retractors and headlight 

illumination is feasible, however local recurrence rates may be considered 

unacceptable with this technique." Transanal Endoscopic Microsurgery 

(TEMS)This method uses a resectascope to give a stereoscopic view of the 

rectum. It is suitable for tumours up to 25cm from the anal verge and is associated 

with a low incidence of morbidity and mortality. The technique is difficult 

and the equipment expensive." Anterior resectionFor high risk early rectal 

cancer in which the previous techniques are unsuitable, an anterior resection 

may be required. Occasionally adequate excision can only be achieved with 

an abdomino-perineal excision.In all these techniques, the aim is to achieve 

a complete excision with a low local recurrence rate and minimal morbidity. 

Depending upon the histology, postoperative radiotherapy may also be necessary. 

It must be emphasised that all patients with early rectal cancer should 

be discussed in a multi-disciplinary meeting to ensure appropriate selection 

and treatment. 

409 speaker 

FRACTIONATION (5X5 AND LONGER SCHEDULE!), CONCOMITANT 

CHEMOTHERAPY AND TARGETED AGENTS, TARGET VOLUME, 

SIDE EFFECTS 

B. Glimelius 1 

1 UPPSALA UNIVERSITY HOSPITAL AKADEMISKA SJUKHUSET, Department 

of Radiation Oncology, Uppsala, Sweden 

Radiotherapy has an important role in addition to surgery in the management 

of primary rectal cancer. The main purposes are to decrease local recurrence 

rates in primarily resectable cancers and allow radical surgery in the 

non-resectable tumours. It has then been hoped that also survival will be 

improved. In addition, many have during the past decade stressed that yet 

another relevant endpoint is sphincter preservation rates.Through the past 

decades, many, sometimes also large randomised clinical trials have been 

performed and our knowledge concerning rectal cancer radiation is extensive. 

Still, many controversies exist. Some of these controversies are not 

based upon a lack of solid evidence. In other aspects, more clinical studies 

are needed. Staging of newly diagnosed rectal cancer has become more 

and more important in order to stratify patients according to risk category. A 

group of early rectal cancers, preferably T1-2, some T3a/b and N0 can easily 

be managed without radiotherapy, provided the surgery is properly done. 

The local recurrence rates in this favourable (good) group should be less than 

5%. A more advanced group (low tumours T3 high tumours T3c/d N0-N2 

can be managed with short course radiotherapy followed by surgery provided 

the crm is not threatened. If surgery was the only treatment in this intermediate 

group (bad), a local recurrence would be seen in more than 10% of 

the patients, a figure reduced by more than 50% by the radiotherapy. In the 

most advanced tumours, T4a or crm+, radiochemotherapy is the preferred 

treatment although short-course radiotherapy with a delay is a valid option 

in patients not properly tolerating the radiochemotherapy. The addition of 

chemotherapy to long-course radiotherapy is established after the results of 

three large randomised trials. Targeted agents are still experimental in addition 

to the radiochemotherapy. A direct head-to-head comparison between 

short-course 5 x 5 Gy and long-course 25 x 2 Gy is ongoing.In order to decrease 

acute and particularly late toxicity, adequate target volumes should 

be used. Studies having explored the patterns of recurrence have found that 

the target volumes used most recently could potentially be reduced, but not 

very much in order to prevent most of the recurrences. The target volumes 

should be drawn more individually than has been the case in the past. We 

know the scale of late morbidity from the trials done during the 1980s 1990s. 

Even if it can be suspected that it is less with presently used techniques, further 

improvements are possible, for example using IMRT, including IMPT and 

IGRT. 

410 speaker 

PERIOPERATIVE SYSTEMIC TREATMENT FOR RECTAL CANCER: 

POSSIBLE STANDARDS, AND NEW 

H. Schmoll 1 

1 MEDICAL SCHOOL HANNOVER, Hannover, Germany 

Rectal cancer is a very frequent disease since about 45 % of patients is colorectal 

cancer are those having rectal cancer. In addition, colorectal cancer 

is the most frequent cancer type for male and female in central Europe. The 

survival of stage II and III rectal cancer is about 60%, and needs definitively 

improvement. It has been clearly shown in all randomised trials in the last 10 

years that after optimisation of local treatment by TME surgery and locoregional 

(chemo)radiotherapy the local relapse rate is significantly and clinically 

highly relevant decreased; however, without influence to distant metastases, 

and therefore survival. The only mean to improve survival is systemic treatment. 

The EORTC trial has shown that preoperative 5FU in conjunction with 

radiation as well as postoperative 5FU or both together has some influence 

on relapse free and overall survival. The QUASAR trial has shown that in 

stage II rectal cancer postop 5FU plus or minus radiation is able to significantly 

improve the survival, as well as some other smaller trials have shown 

the same type of information whereas the Netherlands trial did not show any 

difference, but the accumulated data show evidence for the need of the systemic 

application of 5FU as adjuvant treatment as in colon cancer. However, 

5FU is a very weak chemotherapy to prevent distant metastases and combination 

chemotherapy is urgently needed to be investigated prospectively in 

colon cancer. In addition, combination chemotherapy is very well tolerated in 

combination with radiation before surgery. Most promising is the combination 

of iv or oral 5FU (capecitabine) plus oxaliplatin plus radiation, 4 months after 

surgery. The addition of antiangiogenic strategies, in particular bevacizumab, 

to preop chemoradiation as well as postop chemotherapy is of high interest 

and currently investigated in phase II trials with promising results. The combination 

of combined chemotherapy plus radiation plus EGF-receptor antibody 

is more complex since kras-mutation in the primary tumors has a negative 

impact on the efficacy as well a potentially negative interaction on this combination 

plus radiation. Currently, the PETACC 6 trial in Europe and the NSBAP 

trial in United States are investigating the additional value of oxaliplatin to iv 

or oral 5FU.


Molecular imaging: from structures to treatment 

planning 

411 speaker 

ASPECTS OF TUMOUR BIOLOGY AS IMAGED BY PET: CURRENT 

EVIDENCE AND PROSPECTS 

M. Piert 1 

1 UNIVERSITY OF MICHIGAN MEDICAL CENTER, Department of Radiology, 

Ann Arbor, MI, USA 

Biological information derived from positron emission tomography (PET) is increasingly 

been proposed for target volume definition in radiation treatment. 

Currently, F18-labelled fluorodeoxyglucose (FDG) is the only widely accepted 

PET tracer for the visualization and quantification of the increased glucose 

consumption known to exist in various malignancies. The clinical value of 

FDG is most appreciated for evaluation of response to treatment, but may 

also serve as a distinct target in radiation treatment. However, other tracers 

that evaluate specific metabolic pathways or the microenvironment including 

the perfusion of malignancies are proposed for radiation treatment 

planning purposes as well. Such tracers include C11-Methionine (MET), 

F18-Fluorothymidine (FLT), and C11-Choline (CHOL), all related to certain 

aspects of tumour proliferation. Also, much attention has been paid to PET 

tracers depicting hypoxia as enhanced tracer uptake would predict radioresistance, 

and thus non-response to conventional radiation treatment and certain 

chemotherapy drugs. Accordingly, strategies including radiation boost to the 

hypoxic subvolumes of malignancies have been proposed in order to overcome 

hypoxia-induced radioresistance. While there are many exciting emerging 

imaging techniques based on biological information derived from PET, further 

validation is essential before they can safely be applied for treatment selection 

and planning purposes. As an introduction to this important topic, the 

presentation will focus on the biological basis for such approaches, current 

evidence for clinical applicability to radiation oncology, and future prospects. 

412 speaker 

PITFALLS OF PET IMAGING FOR TARGET DEFINITION IN RADIA- 

TION ONCOLOGY 

J. Lee 1 , X. Geets 1 , V. Grégoire 1 , A. Bol 1 



The purpose of PET in radiation oncology is multiple. Important applications 

are for instance diagnosis (lesion localization), target delineation, and 

detection of tumor heterogeneity. PET-based diagnosis is widely used; target 

delineation and heterogeneity detection are still active research domains. 

Leaving all biological aspects of PET aside, we focus on the technical limitations 

of existing PET systems, which affect the delineation quality.Like any 

other imaging modality, PET can be described by several properties. As each 

pixel corresponds to a measurement, its intensity value is corrupted by statistical 

noise, which is characterized e.g. by a signal-to-noise ratio (SNR). 

As delineation tries to classify pixels (e.g. tumor vs. healthy), specificity and 

sensitivity are useful quantities as well. From the optical standpoint, resolution 

is a key property; it is described by the full width at half maximum 

(FWHM) of the point-spread function (PSF). A low resolution degrades the 

SNR and the specificity/sensitivity.For PET involves high-energy photons and 

must cope with low statistics due to dose limitation, the resolution and SNR 

are low compared to e.g. CT. This leads to blurred and noisy images. Blur and 

noise in the reconstructed image depend both on hardware and software aspects. 

Corrections applied to the data (for scatter and random coincidences, 

dead time, attenuation, etc.) are crucial, as is image reconstruction. Each 

manufacturer develops its own reconstruction algorithm and many settings 

affect the image properties. Usual protocols achieve a tradeoff between quality 

and reconstruction speed that is acceptable for diagnosis, not for target 

delineation.We show that: 1) delineation accuracy depend on the resolution 

and SNR; 2) threshold-based delineation cannot work optimally if the background 

or target activities are not uniform, or if the target is not spherical; 

3) the optimal threshold depends on both the sphere diameter and the PSF 

FWHM. Finally, we suggest that the acquisition and reconstruction protocols 

can be specifically adjusted in order to apply image restoration techniques 

(e.g. resolution recovery). The interest in these techniques is rising, because 

tackle the delineation problem with a sound approach that takes into account 

the image properties. We present some delineation results with such a technique, 

and demonstrate the accuracy improvement.In conclusion, the quality 

of PET-based delineation depends on two important image properties: the 

SNR and the resolution. The acquisition and reconstruction protocols can be 

adapted to meet the specific requirements of delineation in terms of image 

quality. Additional image processing can compensate for the intrinsically low 

resolution of PET and increase the delineation accuracy. 

413 speaker 

S 135 

FUNCTIONAL IMAGE GUIDED RT IN THE CLINIC: EVIDENT 

BENEFITS 

M. Mac Manus 1 

1 PETER MACCALLUM CANCER INSTITUTE, Department of Radiation 

Oncology, East Melbourne, Australia 

The functional imaging technology with the greatest impact on radiotherapy 

(RT) is PET scanning. Promising technologies such as magnetic resonance 

(MR) spectroscopy as yet have no significant clinical role. The most widely 

used PET radiopharmaceutical, 18 F-fluorodeoxyglucose (FDG), is excellent 

for imaging a broad range of malignancies commonly treated with RT, including 

non-small cell lung cancer (NSCLC), oesophageal cancer, head and neck 

cancers and the lymphomas. PET has two inseparable roles in RT patients, 

namely staging and RT planning. A single PET scan should serve both purposes 

if it is known that the patient is to be treated with RT. The scan should 

be performed in the treatment position with immobilisation devices in place. If 

the patient remains a candidate for RT after PET, images can be transferred 

to the RT planning computer for contouring. For many cancers, especially 

NSCLC, FDG-PET-assisted staging is much more accurate than conventional 

staging. PET frequently changes lymph node staging compared to CT based 

staging, which relies on the unreliable parameter of lymph node size. When 

PET staging is demonstrably more accurate than conventional staging, PET 

should be used routinely for RT planning. There are already evident benefits 

from the use of PET in patient selection and for RT planning in NSCLC. 

PET excludes about 30% of patients with incurable disease from futile RT. 

PET-staged patients have better survival than patients treated without PET. 

Survival appears improved largely because patients with extensive disease 

are excluded but PET may also contribute to this effect through better RT 

planning. All published studies in NSCLC show that PET or PET/CT-based 

RT planning is significantly different from CT based planning, in a percentage 

of cases that ranges from 27% to 100%. PET-based RT planning helps to 

avoid geographic miss of regions or lesions not seen on CT and can minimise 

unnecessary irradiation of tissues that do not contain tumour, such as 

atelectatic lung. Intensive study of PET-based RT planning is under way in 

other malignancies. The role of PET varies between different tumour types. 

In head and neck cancer for example, PET increases the accuracy of lymph 

node staging but PET-based contouring of the primary tumour can be difficult 

when differences between PET, CT and MRI scans of the same lesion cannot 

be resolved. The literature on PET-based RT planning is scarce in other 

malignancies, but it appears to be especially promising in oesophageal carcinomas 

and some types of lymphoma. Novel approaches to the use of PET in 

RT planning are being explored. These include hypoxia imaging with agents 

such as 18F-fluoromisonidazole which could potentially facilitate "dose painting" 

of radioresistant hypoxic tumour sub-volumes and the use of FDG-PET 

imaging during RT to facilitate "response adapted RT". 

Respiratory surrogates and tumour motion 

414 speaker 

INTRA- AND INTERFRACTION MOVEMENT OF TUMOURS 

J. J. Sonke 1 


HOSPITAL, Radiotherapy, Amsterdam, Netherlands 

Large geometrical uncertainties are associated with radiotherapy treatment 

of tumors in the thoracic and upper abdominal region. Next to uncertainties 

in target definition, positional variability of the tumor represents an important 

geometrical uncertainty. Both intra- and interfractional position variability 

have three major components: 1) setup variation, i.e., differences between 

the planned and actual position of the overall anatomy, 2) base line variation, 

i.e., differences between the planned and actual position of the time weighted 

mean tumor position relative to the bony anatomy and 3) (variation in) respiratory 

motion, i.e., differences between the planned and actual position of 

the tumor over the respiratory cycle relative to its base line. Setup error and 

baseline variation are similar in size both interfractionally (~4 mm, 1 SD) and 

intrafractionally (1-2 mm, 1 SD), and similar in size for the systematic and 

random error. Interfractional variation of respiratory motion is generally small 

(1 mm, 1 SD), while the intrafractional component is patient dependent (< 3 

mm, 1 SD for 65% of the lung cancer patients). Moreover, respiratory motion 

represents a random error relative to its baseline position and has therefore a 

limited impact on the delivered dose to the tumor. An overview will be given of 

image guided correction strategies to manage intra and interfraction position 

variability of tumors and their impact on the required safety margins.


415 speaker 

IMAGE REGISTRATION AND SPIROMETRY FOR TUMOUR TRACK- 

ING 

G. Christensen 1 

1 THE UNIVERSITY OF IOWA, Department of Electrical and Computer 

Engineering and Radiation Oncology, Iowa City, IA, USA 

Breathing motion is a significant source of error in radiotherapy treatment 

planning for the thorax and upper abdomen. Increasing the beam aperture 

is the method used to account for lung motion in conventional conformal radiotherapy 

which increases the risk of delivering radiation dose to healthy 

tissue and critical organs. Several methods have been proposed to account 

for breathing motion induced error such as respiratory gating, couching and 

breath-hold. Image registration methods can be used as a method to track 

lung motion and apply this information for radiotherapy treatment. This talk 

will describe a relationship between tracking lung motion using spirometry 

data and image registration of consecutive CT image volumes collected from 

a multislice CT scanner over multiple breathing cycles. Temporal CT sequences 

collected over 2-3 breathing cycles were analyzed in this study. At 

each couch position, 15 image volumes were. Small deformation inverse consistent 

linear elastic (SICLE) image registration was used to register consecutive 

image scans. The log-Jacobian of these incremental transformations 

was computed to give a map of the local expansion and contraction of the 

lung during the breathing cycle. The log-Jacobian images demonstrate that 

the lung does not expand uniformly during the breathing cycle, but rather expands 

and contracts locally during both inhalation and exhalation. Predicting 

the location, motion and compression/expansion of the tumor and normal tissue 

using image registration and spirometry could have many important benefits 

for radiotherapy treatment. These benefits include reducing radiation 

dose to normal tissue, maximizing dose to the tumor, improving patient care, 

reducing treatment cost, and increasing patient throughput.The figure shows 

color coded Log-Jacobian images superimposed on target CT volumes for 3 

individuals, along with their continuous spirometry plot. The images for each 

individual were selected such that similar sections of the lung were shown in 

all images at similar phases of the breathing motion. The top images were 

selected at the RMB location in an exhalation phase, denoted by the red line 

on the continuous spirometry plot. The bottom images were selected at the 

same location, but at an inhalation phase. 

416 speaker 

REAL TIME RESPIRATION/MOTION MONITORING BASED TREAT- 

MENT DELIVERY 

B. Paliwal 1 , D. Tewatia 1 , W. Tome 1 , G. Olivera 1 , T. Mackie 1 

1 UNIVERSITY OF WISCONSIN SCHOOL OF MEDICINE AND PUBLICHEALTH, 

Human Oncology and Medical Physics, Madison, USA 

Objective: Primary objective of this presentation is to describe a technique of 

real time respiration monitoring during the radiotherapy treatment beam deliv- 

ery. It holds the promise of accurate dose delivery to the tumor while allowing 

at the same time reduction in the volume of normal tissue being irradiated 

to high dose. It would enable adjustment of margins to account for motion. 

Radiation treatment at a higher dose will be achieved at a constant level of 

normal tissue toxicity, which can potentially yield increase local control. 

Methods and Materials: Dedicated IMRT optimization can generate a highly 

conformed, non-uniform dose distribution that corresponding to the optimal 

biological effects. If there were no intra-fraction motion management technique 

involved, then the attempt to optimize delivery will most likely smear 

the dose or even worse, the interplay of intra-fraction motion and IMRT beam 

motion will result in hot or cold spots throughout the field. In this presentation, 

we would present different intra-fraction motion management techniques for 

adaptive 4D TomoTherapy/TopoTherapy treatment. 

Some of the examples of variety of motion management approaches are: 

3.5D, Breath hold delivery, Breath synchronization planning and delivery 

(BSD), Gated Tomo delivery (TomoGate), Real time motion adaptive delivery 

(RMAD) and real time motion adaptive optimization (RMAO). Our objective is 

to achieve a free-breathing delivery technique with 100% duty cycle. 

In our study a 5 cm diameter cylinder mounted on a 4D actuator was used to 

simulate motion and verify the Free Breathing 4D treatment delivery for both 

spherical and saddle shaped targets. A real time detector signal based Tomotherapy 

integrated planning and delivery process was implemented. Verification 

film dosimetry based dose distributions and profiles for motion corrected 

and uncorrected treatment delivery were obtained and will be presented. 

Results: Comparisons spherical and saddle shape targets for calculated 

dose distributions and film profiles suggests that with proper jaw width, couch 

speed, and margins it is possible to treat moving targets using Tomotherapy. 

Additionally, in cases where extreme motion occurs, motion-corrected delivery 

could be applied. 

Conclusions: The presented methodology shows that real time motion tracking 

using the therapy beam is feasible. 

417 speaker 

IMPACT OF DIFFERENT BREATHING CONDITIONS ON THE DOSE 

TO SURROUNDING NORMAL STRUCTURES IN TANGENTIAL FIELD 

BREAST RADIOTHERAPY. 

R. Prabhakar 1 

1 INSTITUTE ROTARY CANCER HOSPITAL, Department of Radiation 

Oncology, New Delhi, India 

Adjuvant radiotherapy using tangential fields in breast carcinoma has been 

shown to improve the local control. However, improvement in the treatment 

outcome must always be balanced with the potential risk of long-term complications 

such as late cardiac mortality and radiation induced pneumonitis. The 

challenging parameters which interfere in achieving the treatment outcome 

and complications are organ motion and setup-errors. In the current scenario, 

with more and more breast cancer patients receiving cardio toxic drugs 

like trastuzumab, anthracyclines, etc., it becomes all the more important to 

keep the cardiac radiation dose to as low as possible especially in left sided 

tumors. There are several studies supporting that the risk of cardiac mortality 

is high for patients treated by radiotherapy for left-sided as compared to 

right-sided breast cancer. Respiration is the main culprit responsible for organ 

motion which affects the position of the breast, lungs and heart. There 

are different strategies to combat the respiratory motion during radiation delivery. 

These include gating, applying abdominal pressure, voluntary shallow 

breathing, voluntary deep inspiration, active breathing control (ABC) and 

tumor tracking. Each technique has its own pros and cons.Different breathing 

conditions such as deep inspiration breath-hold (DIBH), normal breathing 

phase (NB) and deep expiration breath-hold (DEBH) have their own effect 

on the dose to surrounding critical structures. Our results have shown a 

considerable reduction in the cardiac dose for left-sided breast cancer due 

to DIBH as compared to NB and DEBH. The average reduction in cardiac 

dose due to DIBH was 64% and 74% as compared to NB and DEBH respectively. 

There is a considerable increase in the lung volume from DEBH to 

NB and also from NB to DIBH. The average reduction in liver dose for rightsided 

breast cancer due to DIBH was 50% and 70% as compared to NB and 

DEBH respectively.Inspiratory breathing phase has been shown to considerably 

reduce the dose to the heart and liver in left-sided and right-sided breast 

cancer patients respectively as compared to the other two breathing conditions. 

Treating the patient in a particular respiratory phase also reduces the 

motion artifacts. Image-guided radiation therapy equipped with ABC or gating 

reduces the problems due to organ motion. In, ABC technique, the patient is 

made to hold the breath for a given period of time monitored by a spirometer 

during which the radiation is delivered. In respiratory gating technique, 

the patient breathing is monitored by a device and radiation is delivered only 

during certain time intervals, synchronous with the patient’s respiratory cycle. 

Both gating and ABC requires sufficient training to the patient before performing 

the procedure. For breast cancer patients undergoing radiotherapy 

by tangential fields, treatment in inspiration phase has been shown to reduce 

the cardiac dose considerably.


Biological modelling in radiation oncology 

418 speaker 

GENE PROFILE COMBINED TO DVH SHAPE AS PREDICTOR OF 

RECTAL BLEEDING 

R. Valdagni 1 

1 FONDAZIONE IRCCS ISTITUTO NAZIONALE DEI TUMORI, Milan, Italy 

One of the implicit assumptions in radiotherapy clinical practice is that radiation 

sensitivity in humankind is uniform. Few exceptions to this statement 

regard the very limited group of individuals affected by genetic disorders such 

as ataxia-telengectasia, Fanconi anemia, Nijmegen breakage syndrome, who 

are exquisitely sensitive to radiation but easily identified by their clinical symptoms. 

However, a number of hints from human studies indicate that the assumption 

of uniform radiosensitivity is incorrect. Inter-patient variability in 

expressing radio-induced toxicity of normal tissues is widely recognized and 

evident in the clinic, suggesting that such a phenomenon might be, at least 

in part, genetically determined. Recognizing the existence of an unidentified 

radiosensitive sub-population could imply two consequences: (1) it should be 

considered unethical to suggest a radiosensitive individual to undergo high 

dose radiation because of the potential severe, debilitating acute and late 

normal tissue injuries; (2) in an analytical study, the presence of an unknown 

radiosensitive sub-population might tend to distort the shape of the doseresponse 

relationship, invalidating its general extrapolation. In prostate cancer, 

several studies using uni-multivariate analysis estimate the risk of gastrointestinal 

morbidity based on dosimetric and clinical variables. For late rectal 

bleeding, although these studies do not definitively clarify the role of some 

clinical variables (e.g. the true influence of diabetes or hypertension or of 

concomitant androgen deprivation), they provide a solid set of dose-volume 

constraints to be observed in order to keep the probability of such morbidity 

reasonably low. When considering dose escalation protocols, it is clearly 

evident that, in spite of utilizing highly sophisticated technology and strictly 

applying dose constraints, 5-10% of our patients still suffer from severe rectal 

bleeding. The use of dosimetric models only may be insufficient and clinical 

as well as biological parameters should also be included in predictive 

tools. Few studies in the literature attempt to identify biological predictors of 

acute/late toxicity in prostate cancer irradiation and look at the potential correlation 

between rectal injury and individual gene profiles (Svensson, PLoS 

Medicine 2006; Hmmerich, Int J Radiat Biol 2006; Cesaretti, Int J Radiat Oncol 

Biol Phys 2007; Peters, Int J Radiat Biol 2008). Based on recent findings, 

where abnormal transcriptional responses to DNA damage were associated 

to acute toxicity in non prostate cancer patients (Rieger, Proc Natl Acad Sci 

2004), in the attempt to identify markers predicting late rectal bleeding, we 

analysed 35 genes involved in DNA-repair or pathways known as targets for 

radiation. Patients were selected within the AIROPROS 0101 trial, a specifically 

designed protocol to study the correlation between late rectal bleeding 

and dosimetric parameters (Rancati, Radioth Oncol 2004). The availability of 

accurate dose-volume information helped to minimize the potential bias due 

to inaccuracy in dose delivery. According to our working hypothesis, individual 

dose volume information coupled to single patient’s gene profile might 

concur to explain, on the basis of DVH quality, unexpected rectal bleeders 

as well as the unpredicted absence of late toxicity in some individuals.Thirty 

pts undergoing high dose conformal radiation with a minimum follow-up of 

48 months were selected: a) 10 pts in the low risk group (V7060%) with G2- 

3 late bleeding; c) 10 pts in the high risk group showing no toxicity (supposed 

"radio-resistant" pts). As control group 10 healthy donors were used. 

Quantitative RT-PCR was performed using Taqman Assays-on-Demand on 

RNA from lymphoblastoid cells (LCL) obtained from EBV-immortalized peripheral 

blood mononuclear cells. Inter-group expression levels and class 

prediction were compared using the BRB ArrayTools. Nine genes were 

significantly down-regulated in "sensitive" pts vs "resistant" pts: AKR1B1 

(p=0.019), UBB (p=0.018), LSM7 (p=0.0016), NUDT1 (p=0.0031), MRPL23 

(p=0.015), PSMD1 (p=0.062), BAZ1B (p=0.042), SEC22L1 (p=0.040) and 

PSMB4 (p=0.0079). A defined cut-off level allowed the identification of the 

"sensitive" pts for 4/9 genes. In addition, 4 genes were significantly upregulated 

in "resistant" pts vs all bleeding pts: DRAP1 (p=0.0025), DDX17 

(p=0.048), RAD23 (p=0.015) and SRF (p=0.024). In all cases it was possible 

to define a cut-off level for the identification of the "resistant" pts.Our 

data seem to confirm Cesaretti’s findings (in brachytherapy) on the possible 

genetic component of rectal bleeding and when more pts will be available, it 

might be reasonable to unveil the double nature of the dose-response relationship 

also for external radiation. The characterization of the independent 

contribution of a single patient’s own genetic makeup to the development of 

late radiation toxicity might lead to the clinical application of predictive tests 

to better tailor treatments to the single patient: (a) avoiding radiation injury 

to highly sensitive patients and addressing them to alternative treatments, 

namely radical prostatectomy; (b) modifying treatment planning introducing 

more stringent DVH constraints to have a reasonably lower risk of morbidity; 

(c) modifying the treatment technique, shifting for example, from conformal 

to intensity modulated radiation; (d) modifying the treatment strategy, e.g. 

adding androgen deprivation to a lower prescription dose; or (e) allowing safe 

dose escalation in non susceptible, "resistant", high risk class patients. 

419 speaker 

S 137 

QUANTEC WORK 

J. Deasy 1 

1 WASHINGTON UNIVERSITY IN ST. LOUIS, Radiation Oncology, St. Louis, 

USA 

QUANTEC stands for ’QUANTitative Normal TissuE models in the Clinic,’ and 

is a large, inter-societal effort (AAPM, ASTRO and a few ESTRO members) 

to review and update normal tissue complication endpoints with an emphasis 

on dose-volume tolerance factors and models. The QUANTEC meeting 

was held in Madison, WI, in October of 2007 and included about 50 radiation 

oncology scientists (physicians, physicists, radiobiologists, and statisticians). 

Papers are being prepared for a special issue of the Int J of Radiat Oncol Biol 

Physics by teams of physicians, physicists, and modelers. The papers review 

the clinical significance of the endpoints, discuss the published data in light 

of study quality, and attempt to synthesize the findings of various groups. 

Gaps in knowledge and potential fruitful directions are highlighted. Clinical 

guidelines for judging the likely toxicity risk of treatment plans are suggested 

where possible. A series of papers discusses the need for further research 

in new areas likely to significantly impact research in this area, including: the 

need for inter-institutional, publicly accessible databases of anonymized treatment 

plans and outcomes; the potential of genetic or epigenetic biomarkers 

to identify patients at high risk for complications and the need to co-analyze 

these with dose-volume data for maximum effect; the potential of conformal 

small-animal experiments as a normal tissue-tolerance platform; the potential 

of imaging methods to provide clues and quantitative tolerance data; and the 

need to combine many different sources of data as part of outcomes modeling 

(imaging, dose distributions, patient-reported outcomes, etc.). An effort 

is made across the papers to quantitatively compare published results where 

possible. Although data are not complete or comparable enough to make a 

transition to fully base clinical practice on present datasets and models, the 

available data and analyses are much more extensive than even just a few 

years ago. This effort has been financially supported by ASTRO and the 

AAPM. 

420 speaker 

TCP MODELS - WHERE ARE WE NOW? 

M. Ebert 1 

1 SIR CHARLES GAIRDNER HOSPITAL, Radiation Oncology, Perth, Australia 

The concept of a ’tumour control probability’ (TCP) is a powerful one in a field 

of medicine that relies on statistics. It defines one of the fundamental objectives 

of definitive radiotherapy, and promises to provide an objective measure 

of the likely outcome of a patient’s or group of patients’ treatment. TCP ’models’ 

are mathematical formulations of the TCP concept. These models have 

been developed on the basis of two principle sources of data, i) mechanistic 

models based on laboratory observations, and ii) empirical models based 

on observation of clinical populations. Considerable effort has been made to 

correlate these two approaches. Currently, a principal objective of research 

into TCP models is to move from a model describing the general response of 

a population, to one which provides an objective estimate of outcome for an 

individual patient. This patient-specific formulation encompasses concepts 

in: - inherent radiosensitivity assessed with molecular markers - spatial and 

temporal distributions of histology and function - detailed spatial and temporal 

dose delivery effects. Recent discoveries in radiation oncology are also 

providing us with opportunities to move from a tumour control ’probability’ to 

a definitive notion of tumour control. Techniques in patient profiling, adaptive 

methods, outcomes assessment and the results of clinical trials to produce 

more definitive and clinically-useful models of tumour response. This talk 

shall conclude with an examination of where progress is being made with 

TCP models. This includes the incorporation into clinically-useful TCP models 

of emerging concepts such as: - specific genomic and molecular effects - 

the influence of inter-cellular signalling - the spatio-temporal influence of dynamic 

dose delivery - ’negative’ TCP (ie., the induction of secondary cancers) 

. 

Late effects of radiation treatment - Psychosocial 

care 

421 speaker 

RADIOTHERAPY AND EFFECTS ON SEXUAL FUNCTIONING 

L. Incrocci 1 

1 ERASMUS MEDICAL CENTER ROTTERDAM, Department of Andrology, 


Prostate cancer affects the lives of thousands of men across Europe and is 

the most frequent non-skin male malignancy in Western countries. Prostate


cancer incidence rates increased by 192% between 1973 and 1992. Two 

main factors have contributed to this situation: the worldwide trend for increased 

longevity in the general population, and the improved level of detection 

due to routine prostate-specific antigen tests. Radiation therapy is 

together with radical prostatectomy the most effective treatment for localized 

disease. Both external beam radiotherapy (EBRT) and brachytherapy can 

be offered as curative options. Published rates of erectile dysfunction (ED) 

following EBRT vary from 7-80%, and after brachytherapy this percentage 

may be as high as 60%. The etiology of ED after radiation of prostate cancer 

is multi-factorial. Vascular, neurogenic and psychogenic factors are often 

reported, though a vascular mechanism seems more likely to be involved. Patients 

treated for prostate cancer still want to enjoy sexual life. Studies have 

shown that up to 79% of men older than 70 years still are sexually active and 

most of these weekly. Intracavernosal injections of a vasoactive drug have 

been used since the 1980s with satisfactory results in patients complaining 

of ED. Since the introduction of sildenafil citrate (Viagra), most patients are 

treated with an oral drug. Sildenafil and tadalafil (Cialis) are effective to treat 

ED in about half of the patients after radiotherapy. Testicular cancer affects 

more often young men in their fertile and sexually active life. Seminoma is 

treated by orchiectomy followed by infradiaphragmatic EBRT. In our survey, 

about 20% of the patients reported less sexual interest, pleasure and activity 

since treatment, and this was not significantly correlated with age. Though 

these percentages were not different from an age-matched control group of 

men without testicular cancer. Fifteen per cent of the patients had ED. Sixtytwo 

per cent found their body had changed after treatment. Patients need to 

be adequately counselled on the effects of cancer treatment on their sexual 

life and relationship, about the different treatment possibilities and reassured 

of being able to enjoy a normal sexual life. Unfortunately sexual counseling 

has not become a routine part of oncology care in most hospitals. In busy oncology 

clinics, where the outpatient visit is focused on addressing prognosis 

and treatment, physicians do not have time to assess quality-of-life. Another 

barrier is the discomfort physicians have to discuss sexuality, though sexual 

counselling should be routinely provided in an oncology clinic. 

422 speaker 

PSYCHOLOGICAL CARE:TOWARDS A DEDICATED UNIT FOR 

TEENAGERS & YOUNG ADULTS WITH CANCER 

M. Mascarin 1 , K. Bianchet 2 , S. Birri 3 , A. Annunziata 2 , E. Byther 4 , E. 

Chimienti 5 , M. Gigante 1 , D. Lombardi 5 , M. Michieli 5 , L. Peratoner 1 , S. 

Scalone 5 , M. Spina 5 , P. Zotti 2 , I. Truccolo 6 

1 

CENTRO DI RIFERIMENTO ONCOLOGICO, Radiation Oncology, Aviano, Italy 

2 

CENTRO DI RIFERIMENTO ONCOLOGICO, Psycho-Oncology Unit, Aviano, 

Italy 

3 

FRIULI VENEZIA GIULIA AGENCY FOR HEALTH, Udine, Italy 

4 

CENTRO DI RIFERIMENTO ONCOLOGICO, Scientific Directorate, Aviano, 

Italy 

5 

CENTRO DI RIFERIMENTO ONCOLOGICO, Department of Medical Oncology, 

Aviano, Italy 

6 

CENTRO DI RIFERIMENTO ONCOLOGICO, Scientific Library, Aviano, Italy 

Background-Objectives: Interest for adolescents/young adults affected by 

cancer has emerged in recent years with improvements in the treatment of 

pediatric tumors, yet not relying on specific protocols for tailored therapeutics 

or psychosocial aspects. National collaborative projects for this population 

are rare. Ours is a cancer research & treatment center endowed with a Youth 

Area since 2006 specifically for adolescents. Our effort was to customize 

treatment, given the complex psychosocial environment, particularly during 

diagnosis and treatment. 

Methods: We analyzed,in a regional pop.1.2 million,how many teens with 

cancer are treated at pediatric or adult facilities in 2005-2007. At the same 

time,we presented a project development strategy for personalized management 

of 14-24 year old patients in which they take part. From early 2007, 

we aided personalization by coordinating team care, finalized in the Youth 

Area Project. It offers more accessible types of structural(patients’ library)or 

social(psychological support)resources. A multidisciplinary clinical approach 

preserves fertility and reduces adverse effects on social & body image. 

Results: In 2007,56 pts were treated in Youth Area with 180 hospitalizations(47% 

DH);15% admissions(1264 days)were due to treatment complications. 

Considering only patients with primary tumor diagnosis or chemoradiotherapy, 

there were 1011 regional admissions in 2005-2006 for 14- 

24 year olds:159(16%)in pediatric cancer units;280(28%)in adult cancer 

units;71(7%)in adult haematology units;90(9%)in pediatric;47(5%)in medical;364(36%)in 

surgical units. When activity began, total admissions were 

453:128(28%)in Youth Area;64(14%)in pediatric cancer;4(1%)in adult cancer;23(5%)in 

adult haematology units;32(7%)in pediatric;18 (4%)in medical;184 

(40%)in surgical units. The majority in pediatric oncology units were 

under 17(90%); instead in the Youth Area they were equally distributed in 

age:14-24 years. 63% came from other areas of Italy and 83% of them were 

enrolled in clinical trials. 

Conclusions: in general, placing young adults in medical institutes for children 

or older adults is inadequate. We argue that care must not only be 

administration of a drug or technique but must take into consideration the 

entire individual. Adolescents/young adults with cancer suffer from a lack of 

progress in outcomes and education among community oncologists. "The 

Youth Area" concept will result in a better clinical, psychological, and logistic 

approach to care. 

423 oral 

"IM SO TIRED, I WONDER WHY?" - A SUPPORTIVE INTERVENTION 

AGAINST FATIGUE USED IN CLINICAL 

A. Holst-Hansson 1 , C. Wändel 1 

1 UMAS, Department of Radiation Oncology, Malmö, Sweden 

Purpose: Studies reveals that radiotherapy induced fatigue is the most common 

side-effect of irradiation, reported in up to 90 % of patients during the 

course of treatment and at follow-up visits. The severity of fatigue increases 

during the course of radiation treatment and reaches its highest levels during 

the second to third week of treatment and can persist for months following the 

completion of the therapy. No intervention was available for these patients at 

the Department of Radiation Therapy in the south of Sweden. Ten patients 

were included in a pilot project in the spring of 2007.The aim was to investigate 

if a supportive intervention could contribute to decreased experience of 

fatigue by patients during radiation therapy. 

Materials: When the primary nurse discovered that the patient was suffering 

from fatigue she started an intervention. The level of fatigue was measured 

by using the Visual Analog Scale, VAS. VAS-line a score of 0-10, higher score 

indicating greater level of fatigue. Fatiguelevel higher than 4 led to start of the 

supportive intervention. The patient receives both oral and written information 

according to a nursing management conducted by the authors. The pamphlet 

"Im so tired, I wonder why" was prepared and the questionnaire of emotional 

distress, from National Comprehensive Cancer Network (NCCN) was translated 

by the authors. Follow-up intervievs was planned in cooperation with 

the patient. The inconveniences experienced by the patient was discussed 

during the follow-up interview. Supportive intervention could contain for example 

contact with a doctor, a dietetic or a counsellor. If needed follow-up 

interviews took place even after treatment course was ended. 

Results: 

1. The support of the oncology nurse according to supportive intervention 

contributed to decreased fatigue levels. 

2. The oral and written information about fatigue contributed to the patients 

ability to manage their fatigue, as the patient gained more knowledge 

about their condition. 

3. The follow-up interview and the questionnaire of emotional distress 

made it possible for the nurse to offer the patient the right support. 

Conclusions: 

1. The positive impact with decreased fatigue levels led to the introduction 

of the supportive intervention to all patients with fatigue who received 

radiation therapy at department. 

2. The supportive intervention is an elementary and cost-efficient 

method.

WEDNESDAY, SEPTEMBER 17, 2008 PROFFERED PAPER 

Award lecture 

Regaud lecture 

424 speaker 

REGAUD LECTURE 

K. Ang 1 




Phase III randomised trials II 

425 oral 

S 139 

DAILY LOW DOSE OF CISPLATIN (P) RADIOCHEMOTHERAPY FOR 

LIMITED SMALL CELL LUNG CANCER (SCCL) : AN EUROPEAN 

LUNG CANCER WORKING PARTY PHASE III TRIAL 

P. Van Houtte 1 , T. Berghmans 2 , B. Prevost 3 , J. J. Laffite 4 , A. Efremidis 5 , 

M. C. Florin 6 , M. Paesmans 7 , N. Leclercq 2 , J. P. Sculier 2 

1 

INSTITUT JULES BORDET, Radiation Oncology, Brussels, Belgium 

2 

INSTITUT JULES BORDET, Department of Intensive Care and Thoracic 

Oncology, Brussels, Belgium 

3 

OSCAR LAMBRET, Radiation Oncology, Lille, France 

4 

CHRU LILLE, Pneumology, Lille, France 

5 

SAINT SAVAS HOSPITAL, Medical Oncology, Athens, Greece 

6 

CH DOUAI, Pneumology, Douai, France 

7 

INSTITUT JULES BORDET, Data Centre, Brussels, Belgium 

Purpose: Cisplatin etoposide and early chest radiotherapy remain the current 

recommendation for the management of limited SCLC. The EORTC Non 

small cell lung cancer trial demonstrated a benefit in term of survival and local 

control when using low daily dose of P. The present phase III trial was 

launched to see the benefit of daily low dose of P compared to the classical 

approach for limited SCCL. 

Materials: Patients with previously untreated pathological confirmed SCLC, 

Karnofsky performance status >60, adequate haematological, hepatic, renal, 

lung and cardiac functions, limited disease after a complete workup including 

brain imaging were eligible. After central randomisation, patients were treated 

with a first course of E (100 mg/m2D1-3) plus P given at 90 mg/m2 on D1 ( 

arm A) or at 6 mg/m2 one hour before each fraction of chest radiotherapy 

(15 times 2.66 Gy) (arm B). After completion of chest RT, patients received 

5 additional cycles of E-P at full dose. The initial plan was to randomise 232 

patients to detect a 10% increase in 2-year survival rate with the P daily dose. 

Results: From 1993 to 2006, 204 eligible patients were randomised (arm A 

104 and arm B 100) without any significant imbalance between both arms. 

Compliance to chemotherapy was better in arm A: 78% completed the 6 

courses compared to 70% in arm B. Furthermore, the total P dose delivered 

during chest radiotherapy was lower in arm B with 15 patients not receiving 

the 15 doses. Most patients received the planned dose of chest radiotherapy : 

90% in arm A and 96% in arm B. In term of toxicity during the radiochemotherapy, 

more leucopenia and nephrotoxicity was recorded in arm A and more 

thrombopenia and esophagitis in arm B. Partial and complete response rates 

were similar in both arms, 84% for arm A and 80% for arm B respectively. 

Two- and 5-years survival rates were 35%, 18% in arm A and 38%, 21% in 

arm B (p=0.48). Pattern of failure was very similar in both arms: locoregional 

failure was respectively 22% in arm A and 26% in arm B, brain metastases 

29% in arm A and 27% in arm B. 

Conclusions: Both arms yield good long-term survival in this multicentric 

trial with early radiochemotherapy. The type of P administration, single high 

dose vs daily low dose, had no impact on survival or local control but well on 

the type of toxicity. 

426 oral 

SINGLE-DOSE (8 GY) VERSUS SHORT-COURSE (8 GY X 2) 

RADIOTHERAPY IN METASTATIC SPINAL CORD COMPRESSION: 

RESULTS OF A PHASE III, RANDOMIZED, MULTICENTRE TRIAL 

E. Maranzano 1 , F. Trippa 1 , M. Casale 1 , M. Lupattelli 2 , R. Bellavita 2 , L. 

Marafioti 3 , S. Pergolizzi 4 , M. Mignogna 5 , G. Silvano 6 , V. Fusco 7 

1 OSPEDALE SANTA MARIA, Radiation Oncology, Terni, Italy 

2 UNIVERSITY HOSPITAL MONTELUCE, Radiation Oncology, Perugia, Italy 

3 OSPEDALE MARIANO SANTO, Radiation Oncology, Cosenza, Italy 

4 HOSPITAL, Radiation Oncology, Taormina, Italy 

5 HOSPITAL, Radiation Oncology, Lucca, Italy 

6 HOSPITAL DE LA ESPERANCA, Radiation Oncology, Barcelona, Spain 

7 HOSPITAL, Radiation Oncology, Rionero in Vulture (PZ), Italy 

Purpose: In a previous randomized trial we showed that the short-course 

radiotherapy (RT) regimen of 8 Gy x 2 was feasible and effective in pts with 

metastatic spinal cord compression (MSCC) and short (

S 140 PROFFERED PAPER WEDNESDAY, SEPTEMBER 17, 2008 

Results: 306 (94%) pts were assessable, 150 treated with the short-course 

and 156 with the single-dose RT; 21 are not assessable because of early 

death (9 pts), because they were lost to follow-up (10 pts), or refused RT 

(2 pts). Male/female ratio was 198/108, median age 67 yrs (range, 33-87), 

and median KPS 60 (range, 20-100). As shown in the table, no difference 

in outcome was found between the two RT schedules adopted. The median 

duration of response was 5 and 4.5 months for short-course and single-dose 

RT (p=0.4), respectively. The median overall survival was 4 months for both 

regimens. The incidence of toxicity per group is under evaluation and can be 

reported during the ESTRO meeting. 

Conclusions: Both RT schedules adopted were feasible and effective in pts 

with MSCC and short life expectancy. 

Molecular biology in head and neck cancer 

427 oral 

THE MOLECULAR PREDICTORS OF LOCO-REGIONAL TUMOR 

CONTROL AND DISTANT METASTASES IN A RANDOMIZED CLINI- 

CAL TRIAL ON 7-DAYS-A-WEEK POSTOPERATIVE RADIOTHERAPY 

FOR SQUAMOUS-CELL HEAD AND NECK CANCER 

R. Suwinski 1 , M. Jaworska 2 , B. Nikiel 2 , M. Bialas 2 , M. Bankowska- 

Wozniak 3 , A. Mucha-Malecka 4 , W. Majewski 1 , K. Skladowski 1 , L. 

Miszczyk 1 , D. Lange 2 

1 CENTER OF ONCOLOGY, Radiation Oncology, Gliwice, Poland 

2 CENTER OF ONCOLOGY, Pathology, Gliwice, Poland 

3 REGIONAL CANCER CENTER, Radiation Oncology, Bydgoszcz, Poland 

4 CENTER OF ONCOLOGY, Radiation Oncology, Krakow, Poland 

Purpose: To identify the molecular and pathological predictors of tumor control 

and distant metastases based on the data from a randomized clinical trial 

on 7-days-a-week postoperative radiotherapy for squamous-cell head and 

neck cancer 

Materials: Between 2001 and 2004 279 patients with high-risk squamous 

cell cancer of the head and neck were enrolled to the trial and randomized 

to receive 63 Gy in fractions of 1.8 Gy given 5- or 7-days-a-week. The 

clinical outcome of a trial has been presented elsewhere (Radiother Oncol 

2007,82,Suppl 1:37). For this report we used 125 pathological samples from 

the trial that were available for immunohistochemical assays. The expression 

of EGFR, nm23, p53, Ki67, cyclin D, and selected pathological features (pTN 

stage, pathological margins, number of invaded neck nodes, tumor grade, 

presence of necrosis and keratosis) were related to the clinical outcome (locoregional 

control or distant metastases) using a multivariate Cox proportional 

hazard regression model. The model was optimized using backward stepwise 

regression. 

Results: High expression of nm23, high number of invaded neck nodes and 

high expression of EGFR appeared to be significantly and independently related 

to impaired loco-regional tumor control (p-values 0.01, 0.01 and 0.05, 

respectively). The other markers and treatment-related parameters did not 

appear significant. When individual molecular and pathological risk factors 

were combined to create a joint "molecular" risk score, such score appeared 

significantly superior in prediction of tumor control compared to "traditional" 

score based on the pathological features. As for metastases-free survival 

the presence of necrosis in tumor, absence of keratosis and high number of 

invaded nodes appeared to be significantly and independently related to increased 

metastases risk (p-values 0.02, 0.03 and 0.05, respectively), while 

expression of the analysed molecular markers did not appear significant. 

Conclusions: These results support the studies which indicate that, contrary 

to some other cancer sites, high expression of nm23 appears to be 

a strong negative predictor of loco-regional tumor control in squamous cell 

cancer of the head and neck. Also, the EGFR expression was strongly related 

to loco-regional tumor control. The conventional pathological markers 

(necrosis, keratosis, invaded nodes) appeared to be the best predictors of 

distant metastases in the analyzed dataset. Combining individual predictors 

in a joint risk score may considerably enhance our predictive ability. 

428 oral 

PREDICTION OF LOCAL RECURRENCE AFTER RADIOTHERAPY 

IN HEAD AND NECK CANCER BY EXPRESSION PROFILING 

M. de Jong 1 , J. Pramana 2 , M. Lacko 3 , C. Peutz-Kootstra 4 , J. de Jong 5 , 

R. Takes 6 , H. Kaanders 7 , E. Schuuring 8 , B. van der Laan 9 , L. van den 

Broek 10 , J. Jansen 11 , C. Rasch 12 , M. L. van Velthuysen 13 , L. Wessels 

14 , R. Grénman 15 , M. van den Brekel 16 , F. Hoebers 12 , A. Begg 17 

1 

THE NETHERLANDS CANCER INSTITUTE, Department of Experimental 

Therapy and Radiation Oncology, Amsterdam, Netherlands 

2 


Therapy and Head and Neck Surgery, Amsterdam, Netherlands 

3 

UNIVERSITY MEDICAL CENTER MAASTRICHT, Otorhinolaryngology and 

Head and Neck Surgery, Maastricht, Netherlands 

4 

UNIVERSITY MEDICAL CENTER MAASTRICHT, Pathology, Maastricht, 

Netherlands 

5 

UNIVERSITY MEDICAL CENTER MAASTRICHT, Radiation Oncology, 


6 

RADBOUD UNIVERSITY MEDICAL CENTRE NIJMEGEN, Otorhinolaryngology 

and Head and Neck Surgery, Nijmegen, Netherlands 

7 

RADBOUD UNIVERSITY MEDICAL CENTRE NIJMEGEN, Radiation Oncology, 


8 

UNIVERSITY MEDICAL CENTER GRONINGEN, Pathology, Groningen, 

Netherlands 

9 

UNIVERSITY MEDICAL CENTER GRONINGEN, Otorhinolaryngology and 

Head and Neck Surgery, Groningen, Netherlands 

10 

LEIDEN UNIVERSITY MEDICAL CENTER, Pathology, Leiden, Netherlands 

11 

LEIDEN UNIVERSITY MEDICAL CENTER, Otorhinolaryngology and Head 

and Neck Surgery, Leiden, Netherlands 

12 

THE NETHERLANDS CANCER INSTITUTE, Radiation Oncology, Amsterdam, 

Netherlands 

13 

THE NETHERLANDS CANCER INSTITUTE, Pathology, Amsterdam, 

Netherlands 

14 

THE NETHERLANDS CANCER INSTITUTE, Department of Bioinformatics, 


15 

UNIVERSITY OF TURKU, Department of Otorhinolaryngology ? Head and 

neck surgery and Medical biochemistry, Turku, Finland 

16 

THE NETHERLANDS CANCER INSTITUTE, Otorhinolaryngology and Head 

and Neck Surgery, Amsterdam, Netherlands 

17 


Therapy, Amsterdam, Netherlands 

Purpose: To find a gene expression profile that will accurately predict local 

recurrence after radiotherapy in head and neck cancer. This will not only 

give more insight into the molecular processes underlying treatment failure, 

but will also enable clinicians to individualize treatment, leading to increased 

survival and less unnecessary morbidity. 

Materials: We first studied 92 tumors from patients with T3-T4 HNSCC, 

treated with radiotherapy plus cisplatin (RADPLAT). In the present follow-up 

study, we set out to find an expression profile in a matched series of patients 

with and without a local recurrence after radiotherapy alone. We have 

included pre-treatment biopsies from 99 patients with a T1-3 larynx carcinoma, 

representing a more homogeneous group than the RADPLAT series. 

All biopsies were snap frozen in liquid nitrogen. RNA was extracted with RNA- 

Bee and purified using the Qiagen RNeasy mini and RNase-free DNase kits. 

Subsequently, the RNA was amplified and hybridized to Illumina bead arrays. 

Data were analyzed with Biometric Research Branch (BRB) array tools. In 

parallel, we are studying a panel of 30 HNSCC cell lines with a range of radiosensitivities 

in order to define an "intrinsic radiosensitivity" signature for 

this tumor type. 

Results: In the RADPLAT study we showed, using supervised analyses with 

cross validation, that expression signatures could be found which predict locoregional 

recurrences. In addition, a published "high risk" signature (Chung et 

al) was also highly predictive. At the time of writing for the larynx RT alone 

series, 80 frozen samples have been collected and have suitable quality of 

the extracted RNA and percent tumors cells in the biopsy (>50%). The study 

will be completed at the time of the meeting. We will report on unsupervised 

and supervised analyses, and the predictive potential of signatures found for 

RADPLAT and of several published signatures including those for hypoxia, 

proliferation, stem cells, and intrinsic radiosensitivity. At the time of writing for 

the in vitro study, RNA has been extracted from 24 cell lines, with a range of 

radiosensitivities, before and after irradiation. We expect to supplement this 

with 6 more cell lines by the time of the meeting. Signatures which arise from 

this study will be tested on the two clinical series for their predictive potential 

and we will report on these results. 

Conclusions: Prediction of outcome after radiotherapy appears to be feasible 

using expression profiling, although results need validation in independent 

series. In vitro derived signatures have shown promise for a number of 

biological processes (e.g. hypoxia, wound healing), and we will report here


whether in vitro derived radiosensitivity signatures show similar promise in 

this disease type. 

429 oral 

PROGNOSTIC SIGNIFICANCE OF P16 IN LOCALLY ADVANCED 

SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK 

(LA-SCCHN) TREATED WITH CONCURRENT CISPLATIN AND 

RADIOTHERAPY 

H. Lau 1 , D. Hao 2 , M. Eliasziw 3 , S. Lees-Miller 4 , A. Magliocco 5 

1 

TOM BAKER CANCER CENTRE, Radiation Oncology, Calgary, Canada 

2 

TOM BAKER CANCER CENTRE, Medical Oncology, Calgary, Canada 

3 

UNIVERSITY OF CALGARY, Department of Community Health and 

Epidemiology, Calgary, Canada 

4 

UNIVERSITY OF CALGARY, Department of Biochemistry and Molecular 

Biology, Calgary, Canada 

5 

TOM BAKER CANCER CENTRE, Pathology, Calgary, Canada 

Purpose: Human papillomavirus (HPV) associated SCCHN is emerging as 

a distinct clinico-pathologic entity. p16 expression is strongly correlated with 

tumor HPV status. Our aim was to confirm literature results showing p16 positive 

patients are a distinct subset of SCCHN patients with different prognosis 

from p16 negative patients. 

Materials: Records of 91 consecutive LA-SCCHN pts treated at the Tom 

Baker Cancer Centre between August 2000 and March 2005 were reviewed. 

All patients had biopsy proven SCCHN and were treated with concurrent 

cisplatin and radiotherapy. p16 expression was assessed by conventional 

immunohistochemistry (Dako) using a 4-point semiquantitative scale by the 

study pathologist (AMM) without knowledge of the clinical results. 

Results: Formalin-fixed paraffin embedded biopsies adequate for p16 analysis 

were available from 55 pts. 29 patients were p16 positive and 26 were 

p16 negative. p16 positive patients were younger (mean age 52 v 62, p < 

0.001), more likely to be stage IV at diagnosis (83% v 58%, p = 0.04), more 

likely to be never smokers (38% v 8%, p = 0.008), and presented often with 

oropharyngeal primaries (72% v 27%, p < 0001). With a median follow-up 

of 38 months (range 3 to 85), the 5-year overall survival for p16 positive and 

negative patients was 79% and 27%, p < 0.001. Even after adjusting for 

the observed patient differences in a multivariate Cox regression model, p16 

positive remained an independent significant predictor of better survival (HR 

= 0.17, 95% CI: 0.04,0.83, p = 0.028). The 5-year disease-specific survival 

for p16 positive and negative patients was 91% and 34%, p < 0.001. The 

5-year locoregional recurrence rates for p16 positive and negative patients 

were 11% and 60%, p < 0.001. 

Conclusions: Our retrospective results confirm that p16 positive LA-SCCHN 

patients have improved prognosis following concurrent chemoradiation and 

that this should be considered a stratification variable in current and future 

clinical trials. 

430 oral 

VALIDATION OF RADIATION RELEVANT GENE SIGNATURES ON 

TUMOR XENOGRAFT DATASETS 

M. Starmans 1 , D. Zips 2 , A. Yaromina 2 , B. Wouters 3 , M. Baumann 2 , P. 

Lambin 1 

1 MAASTRICHT RADIATION ONCOLOGY (MAASTRO), GROW RESEARCH 

INSTITUTE, UNIVERSITY OF, Maastricht, Netherlands 

2 DEPARTMENT OF RADIATION ONCOLOGY - CENTRE FOR RADIATION 

RESEARCH IN ONCOLOGY, ME, Dresden, Germany 

3 ONTARIO CANCER INSTITUTE/PRINCESS MARGARET HOSPITAL, Toronto, 


Purpose: Proliferation, hypoxia, intrinsic radiosensitivity and ’stemness’ are 

characteristics implicated in determining outcome of radiotherapy. Creation 

of gene-expression signatures related to these phenotypes may thus provide 

valuable information on prognosis and prediction. However gene expression 

studies tend to produce a high rate of false positive findings and thus the application 

of these signatures in the clinic is difficult. Here we have explored 

the possibility of validating published and unpublished signatures on a comprehensive 

dataset of human tumor xenografts. 

Materials: Gene expression profiles (Affymetrix HG-U133 Plus2.0 

GeneChip) of ten human head and neck squamous cell (HNSCCs) xenografts 

were obtained. Gene expression signatures were obtained both from our own 

unpublished data and from other published microarray studies. These are 

signatures for hypoxia (CA9, SLC2A1, Chi et al., Seigneuric et al.), for proliferation 

(Starmans et al.), the wound signature and the "invasiveness" gene 

signature (IGS). The prognostic value of these signatures was tested for various 

endpoints that have been determined in the different xenograft models. 

These include the hypoxic fraction (Pimonidazole hypoxic fraction, pHF), relative 

vascular area (RVA), perfused fraction (PF), BrdU Labelling Index (BrdU 

LI), volume doubling time (VDT), the radiation dose necessary to locally control 

50% of the tumors (TCD50) and the dose necessary to locally control 50% 

of the tumors under clamped conditions (TCD50clamp), A signature score is 

derived for each tumor xenograft, which is used to test the prognostic value 

S 141 

of the signature. To evaluate the extent of the risk of false positive results, we 

developed a method to test batches of a user-specified number of random 

signatures in a datasets. The percentage of signatures demonstrating significant 

prognostic value was assessed. We also specified before hand several 

hypotheses. 

Results: We found the following correlations: Hypoxia signature (Seigneuric 

et al.) - TCD50clamp: p=0.04; Hypoxia (Chi et al.) - PF: p=0.01; SLC2A1 

- TCD50clamp: p=0.01; CA9 - PF: p=0.02; CA9 - VDT: p=0.01; proliferation 

(Starmans et al.) - BrdU LI: p=0.06, Wound - BrdU LI: p=0.01, IGS - RVA: 

p=0.06; IGS - BrdU LI: p=0.03 However we also found that a signature consisting 

of randomly selected genes has an average 30% chance of reaching 

significance for at least one of the studied endpoint. 

Conclusions: This xenograft dataset is an interesting and valuable tool for 

external validation of various signatures. Most of the findings were compatible 

with our hypothesis. However we also found that the risk of false positive 

findings is significant. This confirms our previous conclusion that validation 

of signatures should be performed on several independent datasets to robustly 

assess their prognostic value.(supported by grant KWF, EC Euroxy, 

DFG grants PAK 124, Ba 1433/4, Ba 1433/5). 

431 oral 

THE USE OF PHOSPHORYLATED HISTONE H2AX AS A MARKER 

OF RADIATION SENSITIVITY OF 2 HUMAN SQUAMOUS CELL 

CARCINOMA (HSCC) LINES IN VITRO AND IN VIVO 

A. Menegakis 1 , M. Krause 1 , W. Eicheler 2 , A. Doerfler 1 , A. Yaromina 1 , H. 

Thames 3 , M. Baumann 2 

1 MEDICAL FACULTY CARL GUSTAV CARUS, TECHNISCHE UNIVERSITÄT 

DRESDEN, Radiation Oncology and Radiobiology; OncoRay - Centre for 

Radiation Research in , Dresden, Germany 

2 MEDICAL FACULTY CARL GUSTAV CARUS, TECHNISCHE UNIVERSITÄT 

DRESDEN, Radiation Oncology and Radiobiology; Experimental Centre; 

OncoRay - Centre for R, Dresden, Germany 

3 UNIVERSITY OF TEXAS M.D. ANDERSON CANCER CENTRE, Department 


Purpose: Upon induction of Double Strand Breaks (DSBs), histone H2AX 

is rapidly phosphorylated near the broken ends forming nuclear foci γH2AX. 

We have investigated the induction and kinetics of γH2AX foci and explored 

the potential of using the number of residual γH2AX foci as a marker for 

radiosensitivity in two hSCC in vitro and in vivo. 

Materials: FaDu (moderately sensitive) and SKX (extremely sensitive) were 

used. For the in vitro study, the cells were cultivated until confluence, irradiated 

with single doses (SD) and incubated for 24h. The cells were either 

stained for γH2AX or seeded for colony forming assay. For kinetic experiments, 

cells were irradiated with 4 Gy and stained at several time points after 

irradiation. In the in vivo study, induction and repair kinetics of the foci dephosphorylation 

after SD irradiation were evaluated in oxyganated cells (close to 

perfused vessels) and hypoxic cells (pimonidazole area). The number of foci 

was counted per nucleus by eye. 

Results: The mean number of residual γH2AX foci (24 hours after irradiation) 

in vitro increased lineraly with increasing dose and significantly correlated 

with the cell survival and the expected lethal lesions according to Poisson 

statistics for both cell lines. In vivo in FaDu, the mean number of initial foci in 

hypoxic cells was three times lower than in oxic cells. Kinetics of dephosphorylation 

was similar in both populations and followed exponential decay as in 

in vitro. The induction of foci inversely correlates with the distance from the 

closest perfused vessel. The halftimes of the foci dephosphorylation for oxic 

and hypoxic cells are comparable to those of normal tissues after functional 

assays. The kinetics of the foci dephosphorylation of the SKX are under investigation 

and will be included. Tumor control assays have been performed 

in parallel for both cell lines and will be correlated with the γH2AX data. 

Conclusions: The data suggest that the residual γH2AX foci can be used 

as a reliable marker to indicate cell killing by radiation. Based only on the 

mean number of residual foci cell survival curves can be predicted for both 

cell lines in vitro. Detecting the formation and persistence of γH2AX foci in 

vivo provides a tool to study induction and repair of DSBs in different tumor 

cell populations. The data support that the phosphorylation of H2AX can be 

used as a good method to predict radiosensitivity of tumours both in vitro 

and in vivo.Supported by the 6th framework EU-project BioCare, proposal 

No505785


Prediction and Genomics 

432 oral 

NO ASSOCIATION BETWEEN SINGLE NUCLEOTIDE POLYMOR- 

PHISMS IN THE TRANSFORMING GROWTH FACTOR BETA-1 GENE 

AND BREAST SHRINKAGE AFTER RADIOTHERAPY 

G. Barnett 1 , N. Burnet 1 , C. Coles 1 , C. Baynes 2 , S. Scollen 2 , R. Elliott 

3 3 2 4 4 4 

, C. West , P. Harrington , J. Wilkinson , M. Moody , C. Wilson , C. 

McQuade 4 , G. Wishart 5 , A. Dunning 2 

1 

ADDENBROOKES HOSPITAL, University of Cambridge Department of 

Oncology, Cambridge, United Kingdom 

2 

STRANGEWAYS RESEARCH LABORATORY, Cancer Research-UK Department 

of Oncology, Cambridge, United Kingdom 

3 

THE UNIVERSITY OF MANCHESTER, Academic Radiation Oncology, 

Division of Cancer Studies, Manchester, United Kingdom 

4 

ADDENBROOKES HOSPITAL, Department of Oncology, Cambridge, United 

Kingdom 

5 

ADDENBROOKES HOSPITAL, Cambridge breast Unit, Cambridge, United 

Kingdom 

Purpose: The ultimate goal of radiogenomics is to develop genetic profiles 

that allow individualisation of radiation treatment. The candidate gene 

approach has the attraction that it assumes, and can test, simple biological 

hypotheses.Two small studies have shown a correlation between single 

nucleotide polymorphisms (SNPs) in the transforming growth factor beta-1 

(TGFβ-1) gene and late radiotherapy normal tissue damage in breast cancer 

patients. We sought to confirm this relationship using another SNP in TGFβ- 

1 (rs4803455) which is strongly correlated with both the C-509T and L10P 

SNPs previously studied. 

Materials: The TGFβ-1 SNP (rs4803455) was genotyped in 431 breast cancer 

patients who were recruited to both the RAPPER (Radiogenomics: Assessment 

of Polymorphisms for Predicting the Effects of Radiotherapy) and 

Cambridge Breast IMRT trials. The clinical endpoint, breast shrinkage, was 

assessed two years after radiotherapy using a validated photographic technique 

with a three-point scale: "no change", "some shrinkage" or "marked 

shrinkage". Regression analysis was used to relate photographic score with 

genotype. 

Results: On photographic assessment, 127 patients showed some degree of 

breast shrinkage, whilst 25 patients showed marked breast shrinkage. There 

was no significant association between SNP rs4803455 genotype and breast 

shrinkage after radiotherapy (P = 0.93). 

Conclusions: Although small studies have reported a correlation between 

late tissue damage after radiotherapy and SNPs in TGFβ-1, this larger study 

found no such association. This illustrates the limitations of the candidate 

gene approach. Recently, Genome Wide Association Studies (GWAS), with 

more stringent levels of significance and consequently larger sample sizes, 

have generated more reproducible associations between genotype and cancer 

risk. Genome Wide Association Studies may therefore be more effective 

in radiogenomics than the candidate gene approach. 

433 oral 

RADIOGENOMICS AND RAPPER: DESIGNING STUDIES WITH 

SUFFICIENT POWER 

N. Burnet 1 , R. Elliott 2 , A. Dunning 3 , G. Barnett 1 , P. Pharoah 3 , D. 

Dearnaley 4 , C. Coles 1 , C. West 5 

1 

UNIVERSITY OF CAMBRIDGE, ADDENBROOKE’S HOSPITAL, Oncology, 


2 

CHRISTIE HOSPITAL, Division of Cancer Studies, Manchester, United 

Kingdom 

3 

STRANGEWAYS RESEARCH LABORATORY, CRC Human Cancer Genetics 

Group, Cambridge, United Kingdom 

4 

ROYAL MARSDEN NHS FOUNDATION TRUST & THE INSTITUTE OF CANCER 

RESEARCH, Academic Unit of Radiotherapy 

Kingdom 

Oncology, Surrey, United 

5 

CHRISTIE HOSPITAL, Division of Cancer Studies, manchester, United 

Kingdom 

Purpose: The success (or failure) of radiogenomics will depend on our ability 

to design and perform studies with sufficient power to detect real effects. 

The ultimate goal is to develop genetic profiles that allow individualisation of 

radiotherapy (RT) to optimise tumour control while reducing toxicity. The candidate 

gene approach, though attractive (and traditional) assumes we fully 

understand the biology of normal tissue response and can name most of the 

genes involved neither of these assumptions is safe. 

Materials: RAPPER is a large UK radiogenomics study testing the hypothesis 

that single nucleotide polymorphisms (SNPs) in multiple genes are responsible 

for individual variation in normal tissue response to RT. Clinical data 

and blood samples are being collected from breast, prostate, gynaecological 

& rectal cancer patients treated in formal, mostly randomised, studies of curative 

RT. EDTA blood samples are stored from 1833 patients (83% of target), 

with surplus held for future work. High-quality DNA has been extracted 

from 1429/1436 samples (>99%), average yield 195±67 µg, range 22-494 

µg. RAPPER was designed as a candidate gene study using SNP-tags, focusing 

on cell-cycle checkpoint control, DNA damage response and cytokine 

pathways. An initial analysis on 431 breast cancer patients indicates no relationship 

between the candidate TGFβ1 509CT polymorphism and breast 

shrinkage, contrary to previous reports (Barnett et al, this meeting). 

Results: Since RAPPER’s inception, Genome Wide Association Scans 

(GWAS) have become practicable. These utilise high-throughput genotyping 

of up to a million SNPs simultaneously and require no a priori knowledge 

of the position or function of risk alleles. Recent GWASs for susceptibility 

to breast, prostate and colorectal cancers have identified genes of unknown 

function and even non-coding DNA regions (Easton et al, Eeles et al, & others). 

This weakens the argument for candidate gene studies. 

Conclusions: Although GWASs require large patient numbers, they use a 

multi-stage approach that reduces the amount of genotyping required without 

sacrificing statistical power. A new power calculation for RAPPER suggests 

a phased approach would require 2,000 patients in a first phase to derive a 

signature, then a further 8,000 in a confirmation phase. Further studies would 

be required to test the ability of the SNP signature to predict outcome, and 

evaluate sensitivity, specificity and predictive errors. This will require international 

collaboration, but such a design will have the advantage of reproducibly 

identifying new genes associated with RT toxicity. 

434 oral 

ASSOCIATION OF SINGLE NUCLEOTIDE POLYMORPHISMS (SNPS) 

IN TWO SELECTED GENES WITH RISK OF ACUTE REACTIONS OF 

BREAST CANCER PATIENTS AFTER RADIOTHERAPY 

U. Höller 1 , K. Derda 2 , K. Borgmann 3 , P. Feyer 1 , E. Dikomey 2 , A. Raabe 

2 

1 VIVANTES KLINIKUM NEUKOELLN, Department of Radiation Oncology and 

Nuclear Medicine, Berlin, Germany 

2 UNIVERSITY MEDICAL CENTER HAMBURG, Lab. of Radiobiology Experimental 

Radiooncology, Hamburg, Germany 

3 UNIVERSITY MEDICAL CENTER HAMBURG, Laboratory of Radiobiology 

Experimental Radiooncology, Hamburg, Germany 

Purpose: A small group of patients will always show severe acute effects 

after radiotherapy. It was the aim of this study to test, whether SNPs can be 

used to identify these patients at high risk of clinical acute reactions. 

Materials: Blood samples were selected from 87 patients with breast cancer 

stage I/II, who had undergone breast conserving surgery. Patients were 

treated with 3D-planned tangential photon fields to the breast only, applying 

a mean tumor dose of 50.4 Gy (range 50-50.4; 1.8-2.0 Gy/f) ± boost with 

10 Gy. At 50 Gy (before boost therapy), erythema as a typical acute reaction 

was prospectively evaluated by two observers using the RTOG score. 

Blood samples taken prior to therapy were used to analyse lymphocytes for 

SNPs in TGF1 (C-509T) and in XPD(A751C) using the PCR-RFLP method 

or MALDI-TOF, respectively. 

Results: Acute reaction of grade 2/3 developed in 47 out of 88 patients 

(53%). Breast volume was the only clinical risk factor for erythema: 44% 

of patients with breast volume < 750 cm had erythema as opposed to 66% of 

patients with larger breast volume (> 750 cm) (p=0.0216). For both SNPs, the 

allele distribution was comparable to that known for an European population. 

For patients with SNP in TGF1 the risk of erythema grade 2/3 was clearly 

increased. To exclude the confounding factor, further analysis was restricted 

to the 55 patients with breast volume < 750 cm. The association of SNP in 

TGF1 and erythema was pronounced (83% erythema G2/3 in patients with 

SNP vs 26% in patients without SNP). In contrast, for SNP in XPD, risk of 

acute reaction declined from 50 in patients without SNPs to 39% in patients 

with SNP showing that wild typ-allele might be a risk factor. Combining both 

risk alleles, a clear increase of the risk for acute reaction from 20 % to 90% 

was observed. 

Conclusions: Individual risk of acute reaction after radiotherapy might be 

determined via the identification of specific risk alleles. 

435 oral 

RADIOTHERAPY RESPONSIVE MARKERS IN SEQUENTIAL 

BIOPSY SAMPLES FROM CERVICAL CANCER PATIENTS DURING 

FRACTIONATED RADIOTHERAPY 

M. Iwakawa 1 , T. Ohno 1 , T. Tamaki 1 , S. Kato 1 , M. Nakawatari 1 , T. Imai 1 

1 NIRS, Research Center for Charged Particle Therapy, Chiba, Japan 

Purpose: We previously reported radiotherapy-responsive genes, which 

were revealed by comprehensive transcriptome analysis using the microarray 

technology for sequential biopsies for cervical cancer patients with radiotherapy 

(RT). We found several tens of RT-responsive genes, including 

well-known radiation-responsive apoptosis/cell cycle-related genes, such as 

cdkn1a/p21, CAD, and Bax, and several tens of genes categorized into extracellular 

matrix (ECM), such as HPSE and CD44. In addition, several 

cytokines were also included. In this study, we investigated the possibility 

that some of those molecules, which were changed their expressions by RT, 

might be new biomarkers for the effectiveness of RT. Sequential biopsy sam-


ples were immunohistochemically analyzed before and during RT in cervical 

cancer patients, and the prognostic value of such changes of 15 candidate 

molecules for disease failure after RT were evaluated. 

Materials: Biopsy specimens were obtained from 91 patients with cervical 

cancers before (pretreatment) and 1 week after initiation (midtreatment) of 

radiotherapy. Immunohistochemical studies of 15 candidate markers, which 

were in RT-responsive genes or related with those genes, were performed to 

detect protein expression using an automated streptavidin-biotin immunoperoxidase 

staining system. Positive area/numbers of cells proportion (%) of immunostaining 

were analyzed using an image analysis system or the positive 

staining appearance was scored by grading system. Patients were defined 

as good or poor responders based on their two-year disease-free survival. 

Aberrant genomic change, human papillomavirus infection, and p53 status in 

tumor were also evaluated. 

Results: Protein expression of cdkn1a/p21, Bax, p53 and FGF2 in midtreatment 

samples (mid) was significantly higher than in pretreatment samples 

(pre). Protein expression of P-cadherin, ICAD, S100, p73 and VEGF in mid 

was significantly lower than in pre. Discontinuity of laminin staining pattern in 

mid was significantly higher than in pre. The ratio change (mid versus pre) of 

FGF2 expression in poor responders was significantly lower than that in good 

responders (P < 0.05). The number of cases with discontinuity of laminin 

staining pattern at pre was significantly higher in the poor responders (P < 

0.05). 

Conclusions: Using biopsy specimens from pretreatment and midtreatment 

cervical cancers, we revealed significant changes in expression of several 

proteins during fractionated radiotherapy. We also found that some of these 

ratio changes were significantly associated with prognosis. These molecular 

features in sequential biopsy samples might help us to identify patients at high 

risk of disease failure after radiotherapy and to provide tool for personalized 

radiotherapy. 

436 oral 

FDG-AND ACETATE-PET IN RADIOTHERAPY. INSIGHTS IN TU- 

MOUR VOLUME DEFINITION, OXIDATIVE METABOLISM AND 

PERFUSION AND THEIR RELATIONSHIP TO RADIORESPONSIVE- 

NESS 

S. Johansson 1 , S. Aijun 2 , A. Dasu 3 , I. Turesson 4 , J. Sörensen 5 

1 

SECTION OF ONCOLOGY AND NUCLEAR MEDICINE, Department of Medical 

Sciences, Uppsala, Sweden 

2 

UNIVERSITY HOSPITAL, SECTION OF ONCOLOGY, Department of Radiation 

Sciences, Umeå, Sweden 

3 

SECTION OF RADIATION PHYSICS, Department of Radiation Sciences, 

Umeå, Sweden 

4 

SECTION OF ONCOLOGY, Department of Medical Sciences, Uppsala, 

Sweden 

5 

SECTION OF NUCLEAR MEDICINE, Uppsala, Sweden 

Purpose: To evaluate the usefulness of 1-[11C]-acetate positron emission 

tomography (ACE-PET) in head and neck cancer patients treated with radiotherapy. 

Issues that were addressed included detection and delineation 

of gross tumour volumes before radiotherapy in comparison to the results 

obtained using 18F-fluorodeoxyglucose (FDG)-PET. Early ACE deposition is 

proportional to blood flow, while tissue clearance rate is proportional to CO2 

release. We therefore applied repeated dynamic ACE-PET to investigate the 

feasibility of measuring tumour microenvironmental characteristics such as 

oxidative metabolism and perfusion during on-going treatment. 

Materials: Ten patients with histologically verified squamous cell carcinoma 

were investigated by FDG-PET and ACE-PET prior to radiotherapy. The two 

scans were performed on the same or consecutive days. Diagnostic CT 

and/or MRI were performed in all patients. The image data sets were analysed 

both visually and semiquantitatively. All primary tumours and metastases 

were delineated automatically by using the 50% threshold of maximum 

radioactivity corrected for background. The tumour volumes were evaluated 

and compared. In 9 patients tumour oxidative metabolic rate (OXm) and perfusion 

(rF) were assessed by dynamic ACE-PET before and after 15, 30 and 

55 Gy were delivered. Patients were grouped as complete (CR) and partial 

responders (PR) to radiotherapy. 

Results: Tumour volumes delineated with ACE were on average 50% larger 

than the FDG volumes (p


Debate 

How much QA should be done for new radiotherapy 

technologies? 

438 speaker 

INTRODUCTION: HOW MUCH QA SHOULD BE DONE FOR NEW 

RADIOTHERAPY? 

T. Knöös 1 

1 LUND UNIVERSITY HOSPITAL, Radiotherapy Physics, Lund, Sweden 

The ESTRO Physics Committee has had a number of discussions recently 

on the topic of Quality Assurance requirements in Radiotherapy. Specifically, 

the questions of how much QA is required and how often tests should be 

performed have been debated. Historically a number of QA protocols have 

been published which have set out the type of tests, frequency of test and 

tolerances expected. However, as technology becomes more complex these 

protocols may no longer be appropriate. In addition, QA is generally a resource 

intensive process so significant increases in QA requirements can 

divert scarce staff from other potentially important tasks, such as the introduction 

of more efficient treatment approaches. While it is very important to 

assure the accuracy and safety of the patient using complex technology, modern 

treatment devices may be more reliable and accurate than before, raising 

questions about what QA we should be performing and how often. Some of 

the recent thinking is reflected in discussions of cost-benefit and risk analysis 

as applied to QA. In addition there are different philosophies applied to 

specific areas, such as patient-specific QA for IMRT. A debate between Ben 

Mijnheer (NL) and Geoff Ibbott (US) on the topic of quality assurance for new 

radiotherapy technology will be chaired by David Thwaites (UK). After short 

presentations by Ben Mijnheer and Geoff Ibbott a discussion will take place 

with a panel consisting of Edwin Aird (UK), Coen Hurkmans (NL) representing 

EORTC and Per Nilsson (S) and Nuria Jornet(SP) representing the ESTRO 

QA group.Some of the topics that will be covered during the debate include: 

How much QA/QC is required with modern equipment? Patient and/or class 

based QA for modern techniques such as IMRT and IGRT. Cost/benefit of 

QA and clinical audit. Risk analysis of new technologies Who should perform 

different tasks/steps in the QA process? 

439 speaker 

HOW MUCH QA SHOULD BE DONE FOR NEW RADIOTHERAPY 

TECHNOLOGIES - AMERICAN VIEW 

G. Ibbott 1 



440 speaker 

HOW MUCH QA SHOULD BE DONE FOR NEW RADIOTHERAPY 

TECHNOLOGIES - EUROPEAN VIEW 

B. Mijnheer 1 

1 THE NETHERLANDS CANCER INSTITUTE, Amsterdam, Netherlands 



Professional Development 

441 oral 

DEFINING THE FIELD OF RADIATION THERAPIST RESEARCH 

J. Cox 1 , G. Halkett 2 

1 

UNIVERSITY OF SYDNEY, Discipline of Medical Radiation Sciences, 

Sydney, Australia 

2 

CURTIN UNIVERSITY OF TECHNOLOGY, WA Centre for Cancer and 

Palliative Care, Perth, Australia 

Purpose: Few Australian Radiation Therapists (RTs) take lead research 

roles, with a review in 2002 finding that fewer than 1% of the total workforce 

were employed in research. A search of publications indicates this is a 

world-wide problem. This research is the second stage of an Australia-wide 

process to ascertain RTs’ research priorities to enable the development of 

future projects. 

Materials: The Delphi method was used as it has previously been successful 

in identifying research priorities in related fields. The first stage involved 

a questionnaire sent to all radiation oncology departments in Australia, asking 

respondents to identify problems in patient treatment, working with colleagues 

and general radiation therapy areas. The results of this questionnaire 

were used to create a list of research areas which was sent to the 

departments for prioritisation of research areas as the second stage of the 

project. 

Results: For the first stage, 29 of 46 questionnaires were returned (63% response 

rate). Four hundred and nine items were identified, 374 amenable to 

research questions, and 30 uncodable. The research areas generated for the 

second phase questionnaire were grouped into twelve major research categories, 

ranging across technical, patient-centred and management issues. 

Some examples are: Techniques/Equipment; Imaging in Radiation Therapy; 

Patient Education; Symptom Management; Workload; and Manual Handling 

and Occupational Safety. Prioritization of these research areas is now under 

way. 

Conclusions: The excellent response rate to the first phase indicates RTs 

are keen to improve current practice and are interested in a broad range of 

areas. A large amount of the radiation therapist research published to date 

has been limited to the fields of education, professional development and 

role expansion, which neglects major parts of RT practice like evaluation of 

new treatment techniques, development of evidence based practice and improvement 

of patient care. This may be a historical aberration caused by 

the relatively recent arrival of radiation therapy to academia and the lack of 

experienced research mentors in technical and patient-centred areas. To advance 

as a profession, radiation therapists should define their own core field 

of knowledge. The results of this project will provide guidance in the development 

of radiation therapy research. 

442 oral 

THE PRACTICAL IMPLICATIONS OF RADIOTHERAPY TRIALS 

S. Hynds 1 , S. Early 1 

1 CANCER CENTRE BELFAST CITY HOSPITAL, Radiotherapy, Belfast, Ireland 

Republic of 

Purpose: The impact of any radiotherapy clinical trial on a radiotherapy department 

workload depends on a particular protocol. The issues raised by a 

trial protocol can be managed successfully by a Clinical Research Radiographer, 

who is perfectly placed to co-ordinate and facilitate radiotherapy studies. 

This position provides management and flexibility to network with the 

relevant healthcare professionals to identify and recruit patients. The experience 

of the Cancer Centre, Belfast will be discussed in order to demonstrate 

the changes in practice and difficulties in setting up radiation oncology trials. 

Materials: In 2001, a Lead Clinical Research Radiographer was appointed 

in Belfast to support radiation oncology trials. In reality this post was created 

due to the demands of the START trial with a vision to expand the local 

radiotherapy trial portfolio, to attract other researchers. Over the last number 

of years this aim has become a reality with 10 trials open to recruitment 

and 4 trials in follow up. There are now 2 Clinical Research Radiographers 

employed by the Northern Ireland cancer clinical Trials Unit, 1 Research and 

Development Radiographer, 1 Academic Lead for Radiation Oncology/ Senior 

Lecturer/ Consultant Oncologist, 2 Clinical Research Fellows and a number 

of Physicists active in research. 

Results: The total number of patients screened for possible inclusion into 

a radiotherapy or multi-modality trial is 1100 with 385 recruited in the last 

7 years. The studies involve numerous cancer sites and a diverse multiprofessional 

group. Some examples of changes to practice, the patient care 

pathway and solving problems in fulfilling trial entry criteria will be discussed. 

The changes in practice have been initiated by studies such as START, the 

breast radiotherapy trial which facilitated change in breast technique from 

fixed FSD to isocentric technique. There was an additional resource benefit 

from a radiotherapy scheduling perspective as patients were treated on alternate 

days allowing two new patients to commence treatment on the same


week. The role of the clinical research radiographer extends beyond the radiotherapy 

department, influencing the practice of referring surgeons as their 

management may deem certain patients ineligible before they reach the oncologists. 

Conclusions: The impact of radiotherapy studies on workload and resources 

are discussed but the necessity of these studies to improve outcome for patients 

and improve the quality of the service is paramount. The issues of trial 

recruitment, the problems with meeting the entry criteria and the impact of 

time management for certain studies will be discussed. 

443 oral 

PATIENT SAFETY ASSESSMENT AT A RADIOTHERAPY DEPART- 

MENT 

M. Eiras 1 , I. Monteiro Grillo 2 , A. Escoval 3 

1 

ESCOLA SUPERIOR DE TECNOLOGIA DA SAÚDE DE LISBOA, Radiotherapy, 


2 

HOSPITAL DE SANTA MARIA, Serviço de Radioterapia, Lisbon, Portugal 

3 

ESCOLA NACIONAL DE SAÚDE PÚBLICA, Health Systems Management, 


Purpose: Since the Institute of Medicine (IOM) report ”To Err is Human”, 

healthcare organizations have been recognizing the need to adopt strategies 

towards Patient Safety. As it is well recognised, Radiotherapy can treat cancer 

patients but it can also cause them harm. A QA programme can help to identify 

and correct errors that may take place during the radiotherapy pathway. In 

such a complex environment effective leadership, well designed systems and 

well trained professionals are the main issues to develop a culture of safety. 

This research assesses the patient safety culture at a Radiotherapy Department. 

This will allow us to track changes which will be introduced during the 

coming year. 

Materials: We conducted a survey - The Hospital Survey on Patient Safety 

Culture (HSPSC) - that examines patient safety culture from a hospital staff 

perspective and can be completed by all hospital staff members. It was developed 

by the Agency for Healthcare Research and Quality (AHRQ) as a tool for 

assessing patient safety culture, tracking changes in patient safety over time 

and evaluating the impact of patient safety interventions. The survey measures 

seven unit-level aspects of safety culture, three hospital-level aspects 

and four outcome variables. A (re)validation of the translation to Portuguese 

was done. This survey was distributed to all staff members in a radiotherapy 

department. 

Results: The Portuguese version of the HSPSC seems robust and the overall 

response rate was 65% which is considered very good, 45% radiotherapy 

technologists, 19% radiation oncologists, 16% secretaries and 6,2% physicists 

and nurses. The lowest scores were found in the dimensions: management 

support to patient safety, with a overall score (OS) of 35%; communication 

openness, with a OS of 36%; team work across units, with a OS of 34%. 

The highest scores were found in two dimensions: organizational learning, 

with a OS of 62%; overall perceptions of patient safety, with a OS of 63%. No 

events were reported in nearly 100% of the surveys. The overall grade to the 

work area was considered very good to 42% and acceptable to 55% of the 

respondents. 

Conclusions: As it was the first time we assessed patient safety culture in 

this department it became evident that all staff members were very interested 

to participate. When we compared this data with the AHRQ Publication 

No.07-0025- April 2007, all our dimensions were lower but we were able 

to identify some similarities. When we compared the results within the dimension 

organizational learning, the variable ’staff are actively doing things 

to improve patient safety’ had a rate of 71,9% compared to 80%; ’mistakes 

have led to positive changes’ had 48,4% compared to 61% and ’after we 

make changes to improve patient safety, we evaluate their effectiveness’ had 

65,6% compared to 66%. Reflecting on our results we were able to identify 

several areas with urgent need to improvement so we will conduct a panel 

with experts from the staff members in order to identify actions to be taken 

in the near future. A new patient safety culture assessment will be done in 

a six months period which will lead us to create and implement robust error 

reduction mechanisms in our radiotherapy department. 

444 oral 

RTT’S AND DIAGNOSTIC RADIOGRAPHERS: DIFFERENT EDUCA- 

TION, BUT SAME JOB? 

J. T. Olsen 1 , C. Fredheim 1 , S. Levernes 2 , B. Bø 1 


2 RIKSHOSPITALET/RADIUMHOSPITALET, Dept. of Medical Physics, Oslo, 

Norway 

Purpose: The goal of this study was to deal with the competence of diagnostic 

radiographers (bachelor in radiography) compared to that of RTT’s (bachelor 

in radiography + 1-year post grad. course in radiotherapy). We want find 

out how many radiographers that are employed within the radiotherapy centres 

in Norway and which challenges this could lead to. Further on we looked 

closer into these professions to se if they could perform the same job despite 

S 145 

the difference in formal education. Internal training can contribute to diminish 

the difference between the two professions. Our experience from four different 

radiotherapy centres in Norway indicates a variation in which tasks the 

radiographer has permission to accomplish. We also got the feeling of going 

beyond our competence when working as a radiographer in a RTT’s place. 

This has aroused our interest about the competence within the radiotherapy 

centres in relation to the requirements of quality and safety defined by law and 

regulation administered by Norwegian Radiation Protection Authority (NRPA). 

Materials: To approach the problem we made a question form and sent it to 

all the leaders at the ten radiotherapy centres in Norway. The question form 

consists of 17 questions about employment and tasks for the two professions. 

Others materials we have used is the law and regulation of NRPA, the core 

curriculum for both professions and a report on unintended overexposure of 

a patient at the Beatson Oncology Centre in January 2006. 

Results: Today there are a total of 22 radiographers and 305 RTT’s working 

in the radiotherapy departments in Norway. The results from the returned 

question forms show that there is a great variation in which tasks the radiographers 

are allowed to perform. 

Conclusions: Because there are radiographers working in the radiotherapy 

centres, it seems necessary to regulate more formally the type of tasks they 

can perform compared to RTT’s. This have to take into consideration both 

formal education and internal training. We hope that this paper can contribute 

to focus on the radiotherapy profession and clarify the competence of RTT’s 

compared to radiographers. 

445 oral 

EORTC RADIOTHERAPY TECHNOLOGISTS SECTION : INTRODUC- 

TION AND NEWS 

F. Duclos 1 , E. R. O. G. RadioTherapy Technologists Section 2 

1 CHUV, Radiation Oncology, LAUSANNE, Switzerland 

2 EORTC, Radio Oncology Group, Brussels, Belgium 

Purpose: Aims, Structure, Board, Activities and Projects. 

Materials: New structure and objectives The RT Technologists Section of 

the European Organisation for Research and Treatment of Cancer (EORTC) 

Radiation Oncology Group proudly presents its renewed structure and objectives. 

In the near future, the RT Technologists section will be starting new 

projects and participate in the preparation of new trial protocols. It will also put 

an effort into building an European network of RT technologists. According 

to their specific field of expertise, RT technologists will be asked to participate 

in projects, review trial protocols, and present their activities during the 

annual Radiation Oncology Group meetings. RT technologists will also be 

challenged to take on responsibilities regarding the introduction and quality 

assurance of EORTC trials within their own departments. Board The new 

board will consist of 4 persons : in addition to the chairman, the group will 

appoint a new secretary, a projects supervisor and a science supervisor. 

Projects The projects supervisor will play a key role in the initiation of new 

RT Technologists projects. The group will review the standard Radiotherapy 

protocol text and Radiotherapy Form for future EORTC trials. In case of a 

new trial, the edited version of the Radiotherapy protocol text and Form will 

be commented upon by RT Technologists experts. The section is planning 

to initiate supplementary research related to new EORTC trial protocols with 

the aim of proposing independent research projects to be carried out under 

the authority of the EORTC. Science The science supervisor will play a 

key role in the exchange of scientific information among RT Technologists. 

Parallel to the regular Radiotherapy Oncology Group (ROG) meetings, the 

RT Technologists Section will organize international symposia during which 

RT Technologists can present results of their own research activities. The 

symposia will always deal with topical subjects that have significant impact 

on the work of RT Technologists. The symposia will also serve as a platform. 

During interactive sessions, RT Technologists will discuss concepts for 

new research, exchange opinions and comment on various subjects that are 

of special interest for the Section. International representatives and experts 

The RT Technologists Section will put an effort into building an international 

network of RT Technologists. This network will consist of local and national 

representatives, members and experts. Local representatives will prepare 

their own departments for new EORTC protocols. They will monitor the data 

collection process and make sure research data is returned to the EORTC 

conclusively and complete. National representatives connect the board to the 

local representatives and will play an important role in crossing the language 

barrier. RT Technologists from participating institutes can take on responsibilities 

as a member in activities and projects of the Section, while some of 

them will be consulted as experts for reviewing EORTC protocols and take 

part in RT Technologists’ supplementary research. 

Results: One of the Section most important aims is to build a European network 

of RT Technologists. This means there is an opportunity for RT Technologists 

to participate in this network as members, representatives and / or 

experts. Therefor, the Section needs local representatives of departments. 

This implicates responsibilities regarding the introduction of new EORTC trials 

in departments, particularly when these involve additional procedures to 

be carried out by technologists. It also means acting as a contact person 

for the group. Those who have good communication skills and good command 

of the English language, may even be interested in becoming national 

representatives and act as international contact persons.


Conclusions: If, as a Radiotherapy Technologist, you are interested in actively 

participating to Research, you have questions about the EORTC clinical 

trials, want to participate in an international Technologists Network, just join 

us, first by attending this presentation, and then, by registering in the Section 

to be regularly informed about the Section News. 

Symposium 

GENEPI 2 

446 speaker 

GOOD RESEARCH GOVERNANCE AND THE ESTRO GENEPI 2 

PROJECTS 

E. B. van Veen 1 

1 MEDLAWCONSULT, Den Haag, Netherlands 

The GENEPI projects do not differ substantially from many other European 

projects where researchers exchange data and tissue. Diverging regulations 

and ethical traditions in the various European countries provide a complicated 

landscape with hurdles and pitfalls through which the projects have to 

find their way. Informed consent, which is of utmost importance in clinical 

research, has invaded the language of these observational projects as well. 

However, this ’obsession’ with informed consent does not provide a way out 

on the longer run and could even endanger sound observational research. 

Examples of various approaches towards using data and tissue for research 

will be given, reflecting different regulatory and ethical traditions. The way out 

is not further top down harmonisation at the EU level. When the EU tried to 

harmonise these issues, as with the data protection Directive (94/46 EC) and 

the clinical trial Directive (2001/20 EC) it did no achieve harmonisation, but 

especially in the latter case - had added additional bureaucracy especially 

for academic or non-commercial research. The way forward will be good 

research governance which incorporates existing regulations without exaggerating 

them. This good research governance should do something extra. 

It will help to use the most possible flexibility given in the various regulations. 

This requires trust. With good research governance researchers show that 

they merit the trust vested in them by patients and society at large. It aims 

to achieve a fair balance of the interests of all the stakeholders in a transparent 

way. Such research governance should be developed bottom-up, by 

researchers together with the most interested stakeholders, patient organisations. 

It should not become an extra bureaucratic layer. A good research 

governance framework should not establish rules but principles which provide 

for enough flexibility for the specifics of a project, according to the ’comply or 

explain’ principle. The GENEPI projects are in an excellent position to be 

the first European project with an explicit good research governance Code. 

Many of these principles have been implicitly applied in the GENEPI projects 

already. The presentation will spell out the most important principles and 

discuss their application in the GENEPI projects. Though more should be 

done. Suggestions will be given for the development of principles which are 

still under discussion, like ’ownership’ of data and tissue and ’benefit sharing’. 

Issues of intellectual property rights and patents fall in the category as 

well. Any arrangement should be fair towards all concerned: those who have 

invested or contributed to the project in one way or the other and those who 

have made the invention in one way or another. ESTRO-GENEPI Material 

transfer agreements are being developed at the moment but an overarching 

rationale is needed. It is suggested that in the end the yardstick should be 

how it will be guaranteed that the fruits of research will indeed benefit patients 

or the public at large in a solidarity based European healthcare system. Only 

if the ESTRO projects show how they are an essential link for such research, 

they can and should benefit as well as an intermediary structure to guarantee 

their long term sustainability. And a spelled out good research governance 

Code seems the way to show this as well. 

447 speaker 

OVERREACTORS: DEFINITION AND VALUE 

D. De Ruysscher 1 , T. Hoelscher 2 , A. Polanski 3 , V. Grégoire 4 , E. B. van 

Veen 5 , C. Verfaillie 6 , K. Haustermans 7 

1 

MAASTRICHT UNIVERSITY MEDICAL CENTRE (MUCM+), Maastro clinic, 

GROW Research Institute, Maastricht, Netherlands 

2 

UNIVERSITY HOSPITAL, TU DRESDEN, Department of Radiation Oncology, 


3 

SILESIAN UNIVERSITY OF TECHNOLOGY, Computer Engineering, Gliwice, 

Poland 

4 

UCL CLINIQUES UNIV. ST.LUC, Department of Radiation Oncology, 


5 

MEDLAWCONSULT, Den Haag, Netherlands 

6 

ESTRO, Brussels, Belgium 

7 

UNIVERSITY HOSPITAL GASTHUISBERG, Department of Radiation 

Oncology, Leuven, Belgium 

The so-called normal tissue tolerance for radiation was derived from the most 

radiosensitive sub-group of patients. As the incidence of severe, late irreversible 

tissue damage could not exceed 5 %, the 5 % most radiosensitive 

patients thus determined the prescribed radiation doses. However, because 

of this, radiation dose-escalation and therefore a higher chance of local tumor 

control is hampered. Identifying the most radiosensitive group would 

therefore have huge clinical implications. This is the aim of the over-reactor 

study that is part of the GENEPI-II project.We hypothesize that the study of 

normal tissue obtained from that sub-group of patients who exhibit clinical


radiation hypersensitivity will allow us to identify changes in gene profiles (resulting 

either from mutation or altered gene expression patterns) that lead to 

this phenotype. In the first place, we want to establish a tissue bank containing 

skin fibroblasts, whole blood, lymphocytes, plasma and lymphoblastoid 

cell lines from clinically radiation hypersensitive patients. Overreacting patients 

are defined as individuals who developed severe acute or late side 

effects after radiotherapy without concurrent chemotherapy or "biologicals" 

(e.g. interferon), "targeted drugs" (e.g. EGFR or VEGF inhibitors) or radioprotectors 

(e.g. amifostine). Severe acute side effects are CTCAE 3.0 grade 

2 or more occurring at very low radiation doses where these side effects are 

unexpected; CTCAE 3.0 grade 3-4 lasting more than 4 weeks after the end 

of radiotherapy and/ or requiring surgical intervention at any time. Severe 

late side effects are CTCAE 3.0 grade 3-4 occurring or persisting more than 

90 days after the end of radiotherapy. Knowledge of the dose distribution 

should be known, making it clear that the adverse reaction was not due to 

radiotherapy technique or overdose. 

448 speaker 

PHYSICS QA ON THE GENEPI TISSUE AND DATA BANK: IMPOR- 

TANCE AND CHALLENGES 

M. Tomsej 1 

1 EQUAL-ESTRO SAS, Neuilly-sur-Seine, France 

Tissue banks have become an essential infrastructure for biomedical research, 

molecular biology, genomics and proteomics. GENEPI 2 aims at 

the qualitative and quantitative further development of the European tissue 

bank and data base GENEPIENTB, established with EURATOM support in 

FP5. It is dedicated to research in radiation effects and in the genetic determinants 

of the variation in individual radiosensitivity. With tissues from more 

than 4000 patients linked to solid outcome data stored, GENEPI is currently 

the largest infrastructure in this field worldwide. For each tissue, treatment 

data (dose distributions with dose gradients, total dose, dose per fraction) 

and outcome data are recorded. It will be a major objective for GENEPI 2 

to develop the tools to make these rich data easily searchable and available 

for distant querying. Tissues will be collected from a group of patients who 

demonstrated an unexpectedly severe response to RT.Furthermore a host of 

tools had to be developed to enable the upload and conversion to a common 

format of treatment plans and to select in them points of interest for analysis 

such as low dose areas. This would not only facilitate the assessment of the 

quality of the submitted data but also add an attractive new dimension to the 

database as infrastructure for dosimetric research and for the quantification 

of risk for secondary tumours. In addition, a separate database would be 

created for overreactors: patients showing an extreme response to normally 

well tolerated irradiation doses and whose genetic makeup might provide a 

shortcut to identifying the genetic basis of individual radiosensitivity. For this 

group of patients a full range of new procedures for patient selection and 

QA needed to be created and specific ethical issues addressed.Therefore, 

major attention will be paid to all aspects of quality assurance.The specific 

added value of the GENEPI infrastructure for research in radiation effects is 

totally dependent on the reliability of the quality of the documentation related 

to each of the stored tissues. Checking this quality at 3 different levels is the 

main objective of this working package.1. Centers including more than 150 

patients into the GENEPI database.The external audit procedure will have to 

be performed by accepted bodies, e.g. EQUAL-ESTRO, national lab, &This 

audit includes thermoluminescent dosimeters LiF (TLD) measurements.For 

new centers that intend to include more than 150 patients in the database, 

a prospective external dosimetry audit will be required. This audit will have 

to be performed according to the protocol defined by EQUAL-ESTRO including 

reference absorbed dose (following ESTRO recommendations, depth dependence, 

field size and shape dependence (MLC), and wedge transmission 

factor). Typically, this audit will be carried out using TLDs in a water phantom 

at specified dose. The number of Monitor Units to be prescribed will be 

calculated according to the same procedures as used in clinical practice.The 

reading of these dosimeters and the analysis of the results will be performed 

by EQUAL-ESTRO as well as a comprehensive dosimetry report will be issued.2. 

Random dosimetry check of patients included in the databaseTwo 

percents of all patients included in the database will have a posterior dosimetry 

check based on the data stored in the database and data that will be 

requested to the centers. The objective of this check is to verify that the dose 

certified by the providing centers has been actually delivered. In case of disagreement 

between the recorded and the verified doses, additional patients 

will be checked. In case this procedure identifies a systematic deviation between 

the prescribed and delivered dose, a notification will be sent to the 

head of the Radiation Oncology Department. In case this procedure identifies 

random inconsistencies in the delivered dose, the data recorded in the 

database will be tagged and made unavailable for public query.These checks 

will be done after a given inclusion period of e.g. 6-12 months, providing that 

at least 50 patients will have been entered. If not, the check will be postponed 

for another period of 6-12 months.Centers will be asked to provide 

basic dosimetry data e.g. output factors, percentage depth doses, profiles, 

& from the beam energy of the machine that was used to treat the patient 

subject to control. More sophisticated tool such as the EQUAL-ESTRO MU 

verification software (EQUAL-Dose) could be also used. EQUAL-Dose is a 

QA tool intended for independent verification of clinical dose calculations per- 

S 147 

formed with an arbitrary treatment planning system. The DICOM RT Plan is 

exported from the Treatment Planning System to EQUAL-Dose that will then 

calculate the dose in user-specified points, taking into account the geometry 

and characteristics of the used linac. EQUAL-Dose is internet and modelbased, 

i.e. it contains some specific algorithms (multisource treatment head 

and pencil kernel models) that offer a high calculation accuracy (2D, 3D-CRT 

and static and dynamic IMRT), and that demands very limited dosimetry commissioning 

data.3. Comprehensive dosimetry checks for patients deemed to 

be over-reactorsFor patients who are already included in the database with 

a tag "over-reactors", a comprehensive dosimetry check will be performed to 

ensure that the prescribed dose was indeed delivered within a 5% tolerance 

range. These checks will include verifications of the machine used and the 

treatment plan parameters." Treatment delivery machine checkThese checks 

will include dose verifications in a water phantom in different points in reference 

and non-reference conditions according to the EQUAL-ESTRO external 

dosimetry audit, including reference absorbed dose (following ESTRO recommendations, 

depth dependence, field size and shape dependence (MLC), 

and wedge transmission factor). Typically, this audit will be carried out using 

thermoluminescent dosimeters (LiF) in a water phantom at specified dose. 

The number of Monitor Units to be prescribed will be calculated according 

to the same procedures as used in clinical practice." Verification of treatment 

plan parametersIn case of no major dose deviation from the above-mentioned 

checks is found, a "dosimetry reconstruction" will be performed using the parameters 

effectively used to treat the patients. This check procedure will likely 

require a site visit with onsite measurements using ionization chamber (absolute 

dosimetry) and films (relative dosimetry) in a phantom. Practically, each 

treatment field (intensity modulated or not) will be applied onto a phantom, 

following a DICOM RT plan export. Calculated dose distributions and point 

doses (from Treatment Planning System) at certain depth will be compared to 

measured ones.A comprehensive report will be issued after this comprehensive 

dosimetry audit.Only patients for whom the comprehensive dosimetry 

checks will have confirmed that the dose was indeed delivered within 5% of 

the prescribed dose will be tagged proven over-reactors.



Prostate cancer 

449 oral 

UPDATED RESULTS OF SWOG 8794: ADJUVANT RADIATION FOR 

HIGH RISK PROSTATE CANCER 

G. Swanson 1 , I. Thompson 2 , C. Tangen 3 , J. Paradelo 4 , E. Canby-Hagino 

5 , E. Crawford 6 , G. Miller 7 , M. Lucia 7 , J. Forman 8 , J. Chin 9 , E. Messing 

10 

1 

UTHSCSA, Radiation Oncology, San Antonio, USA 

2 

UTHSCSA, Urology, San Antonio, USA 

3 

SWOG STATISTICAL CENTER, Department of Biostatistics, Seattle, USA 

4 

KANSAS CITY COMMUNITY CLINICAL ONCOLOGY PROGRAM, Radiation 

Oncology, Kansas City, USA 

5 

WILFORD HALL MEDICAL CENTER, Urology, San Antonio, USA 

6 

UNIVERISITY OF COLORADO HEALTH SCIENCES CENTER, Urology, Denver, 

USA 

7 

UNIVERISITY OF COLORADO HEALTH SCIENCES CENTER, Pathology, 

Denver, USA 

8 

WAYNE STATE UNIVERSITY SCHOOL OF MEDICINE, Radiation Oncology, 

Detroit, USA 

9 

UNIVERSITY OF WESTERN ONTARIO, Department of Surgical Oncology, 

London, Canada 

10 

UNIVERSITY OF ROCHESTER SCHOOL OF MEDICINE, Urology, Rochester, 

USA 

Purpose: It has been long recognized that men with pathologic stage T3 have 

a higher risk of recurrence than those with organ confined disease. SWOG 

8794 was designed to address whether there was a benefit to adjuvant radiation. 

When first reported and with a median follow-up of 10 years, adjuvant 

radiation was found to increase biochemical control, decrease local failure, 

and although there was a trend toward improvement, the impact on overall 

and metastatic free survival was not significantly improved. We now update 

these data with 38 more deaths and a median follow up of 11.5 years. 

Materials: The primary endpoint of the study was metastasis free survival. 

In addition to other measures of disease status, quality of life was measured 

at baseline and for 5 years in a large fraction of subjects. Within 16 weeks 

after prostatectomy, patients were randomized to adjuvant radiation versus 

observation. Eligibility criteria included any of the following: positive surgical 

margin, extracapsular extension, or seminal vesicle invasion with no clinical 

or histological evidence of lymph node metastasis. Radiotherapy consisted 

of 60-64 Gy directed at the prostate fossa. PSA was not mandated at study 

inception, but was added shortly thereafter and most patients have PSA data. 

Between 1988 and 1997, 425 eligible and six ineligible subjects with pT3 

adenocarcinoma of the prostate were enrolled in SWOG 8794. 

Results: Adjuvant radiation significantly improved metastasis free survival 

(p=0.036; HR 0.74, 95% CI 0.56,0.98), the study’s primary endpoint. Overall 

survival was improved with radiation (p=0.053; HR 0.76, 95% CI 0.57, 

1.00). Fifteen year metastasis free survival was 46% for radiation and 38% 

for observation. For overall survival, it was 47% and 37% respectively. As 

previously reported, radiation therapy also significantly reduced biochemical 

and local failure as well as the need for subsequent androgen ablation (all 

p=20 ng/mL and/or Gleason score ≥4+3 were staged with lymphnode 

dissection and bone scintigraphy (456 patients). In total, 59 patients 

were lost at follow-up. The biologically no evidence of disease (bNED) was 

defined as time to PSA relapse using ASTRO 2006 criteria (nadir + 2 ng/mL). 

Occurrence of side-effects was assessed according to RTOG. 

Results: Results: The mean follow-up was 4.5 years. During this time 84 

patients have died and 33 of them have had a PSA relapse or progressive 

prostate cancer. In the remaining 51 patients, a non-prostate cancer related 

death has been confirmed. The probability of bNED at 5 years was 83%. 

According to 0, 1, 2 or 3 risk factors (defined as T3-stage, PSA ≥10 ng/mL 

or Gleason ≥4+3) the probability of bNED at 5 years was 91%, 90%, 81% 

and 58%, respectively. See figure.The clinical side effects in the urinary tract 

(Uro) were more common than those in the lower gastro intestinal tract (G-I). 

At 4 years follow-up, the frequency of late reactions for Uro grade 3 and G-I 

grade 3 were 10% and 2 %, respectively. 

Conclusions: Conclusions: HDR brachytherapy combined with external radiotherapy 

generates a high probability of bNED in patients with low to intermediate 

risk prostate cancer. High-risk localized prostate cancer is still a 

therapeutic challenge as the vast majority of the patients develop metastases. 

Furthermore, GI toxicity can be regarded as acceptable but the Uro toxicity 

needs to be reduced. Therefore, in 2002 we have implemented a modification 

of the treatment procedure and the Uro toxicity has then significantly 

decreased.


452 oral 

PSA RESPONSE SIGNATURES - SEPARATING THE GOOD FROM 

THE BAD IN PROSTATE CANCER 

D. Lamb 1 , J. Denham 2 , D. Joseph 3 , T. Keen-Hun 4 , J. Matthews 5 , C. 

Atkinson 6 , N. Spry 3 , I. Franklin 7 , S. Turner 8 , D. Bill 2 , M. Ebert 2 , A. 

Steigler 2 , P. Gleeson 2 , C. D’Este 9 , D. Woodhead 2 

1 

WELLINGTON HOSPITAL, Wellington Blood and Cancer Centre, Wellington, 

New Zealand 

2 

CALVARY MATER HOSPITAL, Newcastle, Australia 

3 

SIR CHARLES GAIRDNER HOSPITAL, Perth, Australia 

4 

PETER MACCALLUM CANCER INSTITUTE, East Melbourne, Australia 

5 

AUCKLAND HOSPITAL, Auckland, New Zealand 

6 

CHRISTCHURCH HOSPITAL, Christchurch, New Zealand 

7 

ROYAL BRISBANE HOSPITAL, Department of Oncology, Brisbane, Australia 

8 

WESTMEAD HOSPITAL, Sydney, Australia 

9 

CENTRE FOR EPIDEMIOLOGY AND BIOSTATISTICS, Newcastle, Australia 

Purpose: We sought to determine whether an individual’s PSA descent pattern 

from baseline to nadir (PSA response signature or PRS) after radiation 

treatment (RT) for prostate cancer correlated with the lowness of the PSA 

nadir and the subsequent biological behaviour of the tumour. 

Materials: In the TROG 96.01 trial, 802 eligible patients with T2b,c,3,4 N0 

prostate cancer (PC) were randomized to 0, 3 or 6 months maximal AD 

(goserelin 3.6mg s.c. monthly and flutamide 250mg p.o. tid) commencing 

2 and 5 months prior to XRT (66.00Gy to the prostate and seminal vesicles). 

Serial measurements of serum PSA prior to, during and after treatment were 

mandated. Pattern recognition software was developed to characterize the 

shape of the PSA descent pattern for each trial patient. 

Results: Of the 270 patients treated with RT alone, 249 were observed to 

have one of three characteristic descent patterns: single exponential (PRS 

Type 1), double exponential or polyexponential (PRS Type 2). The 135 patients 

(50%) with PRS Type 2 reached a lower PSA nadir, and demonstrated 

longer doubling times on relapse, compared to PRS Type 1 patients. PRS 

Type 2 patients also had significantly lower rates of local (p=0.0014) and distant 

failure (p


454 oral 

DEVELOPMENT OF NOMOGRAMS TO PREDICT MODER- 

ATE/SEVERE LATE RECTAL BLEEDING IN PROSTATE CANCER 

PATIENTS UNDERGOING 3DCRT 

R. Valdagni 1 , T. Rancati 1 , C. Fiorino 2 , V. Vavassori 3 , M. Baccolini 4 , C. 

Bianchi 5 , L. Menegotti 6 , A. Monti 7 , M. Pasquino 8 , M. Stasi 9 , G. Fellin 10 

1 

FONDAZIONE IRCCS - ISTITUTO NAZIONALE DEI TUMORI, Prostate 

Program, Milan, Italy 

2 

OSPEDALE SAN RAFFAELE, Medical Physics, Milan, Italy 

3 

OSPEDALE DI CIRCOLO, Radiotherapy, Varese, Italy 

4 

OSPEDALE VILLA MARIA CECILIA, Medical Physics, Lugo, Italy 

5 

OSPEDALE DI CIRCOLO, Medical Physics , Varese, Italy 

6 

OSPEDALE SANTA CHIARA, Medical Physics, Trento, Italy 

7 

OSPEDALE SANT’ANNA, Medical Physics, Como, Italy 

8 

OSPEDALE CIVILE ASL 9, Medical Physics, Ivrea, Italy 

9 

OSPEDALE MOLINETTE, Medical Physics, Turin, Italy 

10 

OSPEDALE SANTA CHIARA, Radiotherapy, Trento, Italy 

Purpose: To predict moderate/severe late rectal bleeding (lrb) in prostate 

cancer patients (pts) undergoing 3DCRT by the use of a tool (nomogram) 

that takes into account clinical and dosimetric variables which proved to be 

significant in the AIROPROS 0102 trial 

Materials: Pts treated at doses >=70Gy (ICRU dose: median 74Gy; range: 

70-81.6Gy; 1.8-2 Gy/fr) in AIROPROS 0102, a prospective cooperative trial 

focused on rectal toxicity (tox) in 3DCRT for prostate cancer, were considered. 

Data on 615 pts (follow-up: 36 mos) were analyzed. G2 lrb was 

scored if bleeding occurred >2 times/week or if pts received 1-2 blood transfusions 

and/or laser coagulations; G3 if pts reported daily bleeding.The correlation 

between pre-treatment morbidities, hormonal therapy, drug prescription, 

presence of diabetes or hypertension, abdominal surgery (SURG) prior 

to CRT, presence of acute LGI RTOG tox (aLGI), pelvic nodes and seminal 

vesicles irradiation, mean rectal dose, dose-volume histograms constraints 

(from V20Gy to V75Gy) and G2-G3 lrb was investigated by uni- and multivariate 

(MVA) logistic analyses.Using the R-project software, nomograms to 

predict G2-G3 lrb, were developed using MVA results and the aLGI nomogram 

(Valdagni et al. IJROBP, in press, 2008). 

Results: 25/615 G2 and 17/615 G3 lrb were registered. In MVA V75Gy resulted 

to be significantly correlated with G2-G3 lrb, together with SURG and 

the presence of G2-G3 aLGI. In order to develop a pre-treatment nomogram 

to estimate grade


ies were assessed by two independent reviewers according to the eligibility 

criteria and included in the present meta-analysis. Searches were performed 

without restricting the language of studies retrieved. For statistical analysis a 

weighted estimate (Peto odds or Hazard ratio) of the typical treatment effect 

across studies was computed for survival data. The risk ratio (RR) was used 

as the effect measure for LRTC. Chi-square heterogeneity tests were used 

to test for statistical heterogeneity among trials. In case of statistical heterogeneity 

random effect models were used. Statistical analysis was performed 

with Review Manager (RevMan). 

Results: Seven RCTs published between 2004 and 2007 were identified. 

Five of them reporting data on long term follow up and were included in the 

current analysis. Four published their study results as full length journal papers 

and the remaining as an abstract. Standard RT resulted in a small but 

significant better LRTC compared to RT +EPO (RR 0.90; 95% CI 0.83 - 0.98; 

p=0.01, n=4). The LRPFS measured in three studies was not significantly different 

between both groups (HR 0.75; 95% CI 0.53 - 1.05; p=0.09), As shown 

in the Forest plot the pooled data yielded a significantly better OS for the RT 

without EPO as compared to RT + EPO group (HR 0.73; 95% CI 0.58 - 0.91; 

p=0.005). If we do not consider the two studies (Machtay 2006 and Rosen 

2003) who supplemented iron in the EPO and not in the control group the 

conclusions concerning OS and LRPFS still hold. However, no conclusions 

can be drawn about LRPFS as only one study (Henke 2003) has reported 

this outcome besides Machtay et al. and Rosen et al.. 

Conclusions: Based on these preliminary results of this ongoing Cochrane 

review there is no evidence that the combined treatment of radiotherapy with 

Erythropoietin yields an advantage as compared to standard radiotherapy 

for the treatment of Head and Neck cancer patients. There is even strong 

suggestion that EPO influence negatively the outcome. Publication of long 

term follow up of unpublished studies and analysis of other endpoints as acute 

and late toxicity are essential to make a firm conclusion. 

457 oral 

THE ROLE OF COX-2 INHIBITOR (CELECOXIB) IN COMBINATION 

WITH CHEMO-RADIOTHERAPY IN HEAD AND NECK CARCINOMA 

TO REDUCE ACUTE TOXICITIES, PHASE III ,RANDOMIZED CLINI- 

CAL TRIAL 

M. Aghili 1 , M. Mojahed 1 , A. Kazemian 1 , S. Izadi 1 , F. Farhan 1 

1 CANCER INSTITUTE, Radiation Oncology, Tehran, Iran Islamic Republic of 

Purpose: Chemo-radiotherapy (ChT-RT) induced toxicities such as oral mucositis 

represents a therapeutic challenge frequently encountered in cancer 

patients. This side effects causes significant morbidity and may delay or 

interruption of treatment plan, as well as reduce therapeutic index. Cyclooxygenase 

2 (COX-2) is an inducible enzyme primarily expressed in inflamed 

tissues and tumor. COX-2 inhibitors have shown promise as radio- and 

chemosensitizer and reduce radio-induce toxicities . We conducted a Phase 

III ,Randomized double blind Clinical Trial to evaluate the toxicity and efficacy 

of celecoxib, a selective COX-2 inhibitor, administered concurrently Cht-RT 

for locally advanced head and neck carcinoma. Here in we report the first 

report about the role of COX-2 inhibitor in acute toxicicities. 

Materials: One-hundred-twenty-two patients with stage III/IV (locally advanced) 

carcinoma of the oropharynx, oral cavity, hypopharynx„ larynx or 

nasopharynx who referred to department of radiation-oncology for primary 

treatment were eligible. Patients were treated with chemotherapy (Cisplatin 

weekly or every 3 weeks) concurrently with radiation (66-70 Gy). Celecoxib 

(100 mg qid) was started at the first day of radiotherapy and was given for a 

total of 8 weeks . Acute toxicicities and were evaluated every week by WHO 

scale. 

Results: One hundred twenty two patients were enrolled into the study, 61 

on the Cox2 arm and 61 on the placebo arm. No significant differences were 

observed between treatment groups for any of the baseline subject characteristics. 

17 patients (14%) did not complete the treatment according to the protocol 

(8 from Cox2 group and 9 from placebo group); A significant difference 

in the time of onset of grade 2 mucositis was found between the two groups; 

the median of this time for patients taking Cox2 was 56 days and for patients 

assigned to take placebo was 28 days (p=0.000). Also there was a significant 

difference in the rate of grade 3 mucositis between the two groups. Grade 3 

mucositis was found just in one patient (1.6%) in the Cox2 group compared 

with 13 (21.3%) in the other group (p=0.001).In repeated measure ANOVA 

the mucositis, dysphagia, epidermitis and oral pain score changed significantly 

over the typical 5 weeksin two groups but these changes were more 

sever in placebo group (p=0.000). In the analysis of the overall changes in the 

S 151 

following laboratory parameters: WBC, hemoglobin and platelet and ANOVA 

showed that these parameters decreased over time in both groups without a 

significant difference between groups. 

Conclusions: The results of these study showed that the use of a cox-2 

inhibitor (celecoxib) may reduce acute toxicities of chemoradiation specially 

mucositis in head and neck cancer. 

458 oral 

IMPROVED SURVIVAL AND RESPONSE TO RADIOTHERAPY IN 

HPV-RELATED OROPHARYNGEAL CARCINOMAS - A SUBGROUP 

ANALYSIS OF THE RANDOMIZED DAHANCA 5 & 7 TRIALS 

P. Lassen 1 , J. G. Eriksen 1 , T. Tramm 2 , J. Alsner 1 , S. H. Dutoit 2 , J. 

Overgaard 1 

1 

AARHUS UNIVERSITY HOSPITAL, Department of Experimental Clinical 


2 

AARHUS UNIVERSITY HOSPITAL, Department of Pathology, Aarhus C, 

Denmark 

Purpose: Expression of p16 is highly correlated to infection with HPV in 

oropharyngeal carcinomas. The aim of this study was to evaluate the impact 

of p16 expression on treatment response and survival in a prospectively 

analyzed cohort of Danish oropharyngeal cancer patients treated with radiotherapy 

according to the randomized DAHANCA 5 & 7 trials. 

Materials: Between January 1986 and December 1999 The Danish Head 

and Neck Cancer group (DAHANCA) conducted the nationwide DAHANCA 

5 & 7 randomized trials, focusing on overcoming the disadvantages of tumour 

cell hypoxia and accelerated tumour cell proliferation in relation to radiotherapy. 

(Overgaard J. et al. Radiother. Oncol. 46; 1998:135-146. Lancet 

2003; 362: 933-940). In the present study, 335 oropharyngeal tumour tissues 

from patients enrolled in these trials were evaluated by immunohistochemistry 

for p16 expression. Tumours were classified as p16 positive in case of a 

strong, confluent nuclear and cytoplasmatic staining pattern or p16 negative 

(absence of staining). 

Results: In total, 135 of the 335 oropharyngeal tumours were p16 positive 

corresponding to 40%. No statistical significant differences were observed 

between the p16 positive and p16 negative groups regarding tumour stage, 

gender, and age. Loco-regional tumour control was significantly improved for 

p16 positive tumours compared to p16 negative, with 5-year actuarial values 

of 67% versus 36% (p < 0.0001). A similar beneficial outcome for p16 positive 

tumours was observed for the 5-year actuarial values for cancer specific 

survival (69% versus 35%, p < 0.0001) and overall survival (54% versus 18%, 

p < 0.0001). In a Cox proportional hazard multivariate analysis p16 expression 

remained a very strong independent prognostic factor for loco-regional 

tumour control [OR: 0.34 (95% C.I. 0.23 - 0.50)], cancer specific death [OR: 

0.28 (0.19 - 0.42)] and overall death [OR: 0.32 (0.23 - 0.45)]. p16 was an 

even stronger prognostic factor related to these outcomes than the clinical 

parameters T-stage and Nodal-status. 

Conclusions: Expression of p16 is significantly correlated to improved 

survival and loco-regional tumour control in oropharyngeal cancer patients 

treated with radiotherapy. p16 status proved to be the strongest independent 

prognostic factor altogether and as such it has been implemented as a 

prerandomization stratum in ongoing and future clinical trials initiated by DA- 

HANCA. Presented on behalf of the Danish Head and Neck Cancer group 

(DAHANCA) 

459 oral 

CHARACTERIZATION OF SQUAMOUS CELL CARCINOMAS OF THE 

SUPRAGLOTTIC LARYNX WITH OR WITHOUT MUTATIONS IN TP53 

J. G. Eriksen 1 , P. Lassen 1 , J. Alsner 1 , J. Overgaard 1 

1 AARHUS UNIVERSITY HOSPITAL, Department of Experimental Clinical 


Purpose: Objective: Tobacco smoking is the primary etiology for squamous 

cell carcinomas of the supraglottic larynx and is reported to initiate the carcinogenic 

process by inducing mutations in TP53. However, not all supraglottic 

larynx carcinomas have mutations in TP53 and a distinct molecular 

profile might separate tumors with or without TP53-mutations. The aim of 

the present study was to characterize possible differences in key-proteins in 

supraglottic larynx tumors according to the TP53-mutational status. 

Materials: Methods: Paraffin-embedded formalin fixed pretreatment biopsies 

of 123 patients with squamous cell carcinomas of the supraglottic larynx 

was collected from patients treated with radiotherapy with curative intent 

between January 1986 and December 1999 according to the DAHANCAguidelines: 

66-68 Gy, 2 Gy/fx, 5-6 fractions/week and concomitant radiosensitizer 

(nimorazole). For estimation of TP53-mutations, DNA was extracted 

from the biopsies and screened for mutations in exon 4c-10 of TP53 by DH- 

PLC (WAWE R○). Mutations were further characterized by sequencing. EGFr, 

p16, KI-67, BCL2 and E-cadherin were estimated by immunohistochemistry. 

Data were evaluated by descriptive statistics, Spearman’s test for trend and 

logistic regression analysis. 

Results: Results: 62 carcinomas were wildtype or had silent mutations out-


side the domains, 61 had mutations inside the domains or null-mutations 

leading to stop-codons. The TP53-mutational status was not correlated to 

the expression of E-cadherin, BCL2 and KI-67 or tumor cell differentiation. 

High expression of EGFr seemed to be correlated to tumors with mutations 

in TP53 (p=0.03) and TP53 wildtype tumors had twice as high expression of 

p16 compared to carcinomas with mutations in TP53 (p=0.04). Furthermore, 

logistic regression analysis separating by mutational status, suggested that 

carcinomas with mutations in TP53 had relative higher expression of EGFr 

(p=0.03, RR=2.6 (1.1-6.3)) and lower expression of p16 (p=0.04; RR=0.4 

(0.2-0.9)) compared to wildtype tumors or tumors with silent mutations outside 

the domains. 

Conclusions: Conclusion: The results of the present study suggest that low 

expression of EGFr and high expression p16 might be two of the markers 

that characterize tumors without mutations in TP53. These data are in accordance 

with experimental data and indicate that other factors than tobacco 

(i.e. HPV-virus) might be involved in the carcinogenic process of squamous 

cell carcinomas of the supraglottic larynx. 

460 oral 

PALIFERMIN SIGNIFICANTLY REDUCES SEVERE ORAL MU- 

COSITIS IN SUBJECTS WITH RESECTED LOCALLY ADVANCED 

HEAD AND NECK CANCER UNDERGOING POST-OPERATIVE 

CONCURRENT RADIO-CHEMOTHERAPY 

M. Henke 1 , M. Alfonsi 2 , P. Foa 3 , J. Giralt 4 , E. Bardet 5 , L. Cerezo 6 , M. 

Salzwimmer 7 , M. Whiley 8 , L. Emmerson 8 , D. Berger 9 

1 

UNIVERSITÄTSKLINIKUM FREIBURG, Department of Radiooncology, 

Freiburg, Germany 

2 

INSTITUT SAINTE CATHERINE SERVICE DE RADIOTHÉRAPIE, Avignon, 

France 

3 

SAN PAOLO UNIVERSITY HOSPITAL, Department of Oncology, Milan, Italy 

4 

VALL D’HEBRON UNIVERSITY HOSPITAL, Radiation Oncology Department, 

Barcelona, Spain 

5 

CRLCC NANTES-ATLANTIQUES, Nantes, France 

6 

HOSPITAL UNIVERSITARIO DE LA PRINCESA, Radiation Oncology, Madrid, 

Spain 

7 

EAR-, NOSE- AND THROAT UNIVERSITY HOSPITAL GRAZ, Department of 

General ENT, Graz, Austria 

8 

AMGEN LTD., Cambridge, United Kingdom 

9 

AMGEN INC., Thousand Oaks, CA, USA 

Purpose: Oral mucositis (OM) is a debilitating and often treatment-limiting 

side effect of cancer treatment and is frequently observed in subjects receiving 

combined radio- and chemotherapy (RT/CT) for head and neck cancer 

(HNC). Palifermin (Kepivance R○ , rhu-KGF) reduces severe OM in subjects 

receiving myeloablative therapy and hematopoetic stem cell transplantation 

for hematological malignancies. This study assessed the efficacy and safety 

of palifermin in subjects with resected locally advanced HNC receiving adjuvant 

RT/CT. 

Materials: This multinational, randomized, double-blind, placebo-controlled, 

phase 3 trial, included adults with resected stage II-IVb squamous cell HNC 

receiving adjuvant RT/CT (standard RT 2 Gy/day for 6 weeks (total 60 Gy) 

with an optional boost of 6 Gy and cisplatin 100 mg/m 2 days 1, 22 and optionally 

on day 43). Subjects were randomized 1:1 to receive IV palifermin 

(120 mcg/kg) or placebo once weekly until completion of RT/CT, with the first 

dose 3 days before the start of RT/CT. Randomization was stratified by postsurgical 

residual tumor (R0,R1) and tumor location. The primary endpoint 

was the incidence of severe OM (WHO Grade 3 or 4). 

Results: A total of 186 subjects were enrolled; 92 randomized to palifermin 

and 94 to placebo. The incidence of severe OM (primary endpoint) was significantly 

reduced in the palifermin subjects compared with the placebo subjects 

(51% vs 67%; p=0.027). Median duration of severe OM was 4.5 days (first 

quartile, Q1, third quartile, Q3; 0, 30) in the palifermin subjects and 22 days 

(Q1, Q3; 0, 37) in the placebo subjects, and median time to onset of severe 

OM was delayed in the palifermin subjects compared to placebo (45 vs 32 

days). Incidence of xerostomia at 4 months was increased in the palifermin 

subjects (76% vs 63%). These differences in secondary endpoints were not 

statistically significant after statistical multiplicity adjustment. Severe adverse 

events (AEs; CTCAE grade 3, 4, 5) occurred in 49% of palifermin subjects and 

55% of the placebo subjects. The most frequent (≥5%) treatment-related 

AE reported was erythema (8% palifermin, 1% placebo). Overall survival 

(median follow-up 63 weeks) was compared using Kaplan-Meier curves and 

the stratified log-rank-test, and no difference between subjects was observed 

(p=0.83) 

Conclusions: Palifermin significantly reduced the incidence of severe OM in 

subjects with resected locally advanced HNC undergoing adjuvant RT/CT. 

Target delineation 

461 oral 

THE USE OF PET IMAGING FOR ADAPTIVE BIOLOGICAL IMAGE 

GUIDED RADIOTHERAPY: STRENGTHS AND LIMITATIONS AS- 

SESSED IN ANIMAL MODEL 

N. Christian 1 , A. Bol 1 , M. De Bast 1 , B. Jordan 2 , J. Lee 1 , V. Grégoire 1 



2 UNIVERSITÉ CATHOLIQUE DE LOUVAIN, Biomedical Magnetic Resonance 

Unit, Brussels, Belgium 

Purpose: Biological image-guided radiotherapy aims at specifically irradiating 

biologically relevant sub-volumes within the tumor. PET with various 

tracers is a relevant imaging modality to define such sub-volumes. This approach 

requires that PET imaging is sensitive and specific enough to image 

various biological pathways of interest, e.g. tumor metabolism, proliferation, 

hypoxia,& In this framework, a validation of PET imaging used for adaptive 

radiotherapy was undertaken in an animal model by comparing small animal 

PET images (2.7 mm resolution) with autoradiography (AR) (100 µm resolution) 

in various tumors and in various physiological situations. 

Materials: A special template for imaging tumor-bearing mouse has been 

used. It allows registration between MRI images (Biospec, Brcker), PET images 

(Mosaic, Philips) and Autoradiography (FLA-5100, Fujifilm). After registration, 

the tumors on the PET and AR images were segmented using a 

threshold-based method. The thresholds were selected to obtain absolute 

equal volumes in the PET and AR images. Matching indexes were then calculated 

between the various volumes. The entire imaging process was repeated 

for FSAII tumors (n=5), SCCVII (n=5) and irradiated (35 Gy) FSAII 

tumors (n=5). 

Results: In regions with high FDG activity delineated using high thresholds, 

low matching values 39% ± 12% (mean ± SD) were observed between the 

volumes delineated on the PET images and those delineated on autoradiography. 

The matching values progressively increased when considering larger 

volumes obtained with lower thresholds. The relationship between the matching 

values and the percentage of overall tumor volume was fitted through a 

power regression (r = 0.93). This relationship was non statistically different 

between tumor type or tumor size. The matching improved with higher PET 

resolution (by simulating variations of the Full Width at Half Maximum of the 

PET camera), and vice versa. Extrapolation of the data to human tumors imaged 

with a human PET showed a similar relationship between the matching 

indices and the fractional volume. 

Conclusions: Discrepancies were found between the PET images and the 

underlying microscopic reality visualized by AR images. These differences 

were important when considering small and highly active regions of the tumors. 

Dose painting based on PET images should therefore be carefully 

considered and take these limitations into account. 

462 oral 

ACCURACY OF DIFFUSION-WEIGHTED MRI FOR NODAL STAGING 

AND RADIOTHERAPY PLANNING OF HEAD AND NECK SQUAMOUS 

CELL CARCINOMA. 

V. Vandecaveye 1 , P. Dirix 2 , F. De Keyzer 1 , K. Op de beeck 1 , V. Vander 

Poorten 3 , P. Delaere 3 , E. Verbeken 4 , R. Hermans 1 , S. Nuyts 2 

1 

UNIVERSITY HOSPITALS GASTHUISBERG, Radiology, Leuven, Belgium 

2 

UNIVERSITY HOSPITALS GASTHUISBERG, Radiation Oncology, Leuven, 

Belgium 

3 

UNIVERSITY HOSPITALS GASTHUISBERG, Department of Otorhinolaryngology 

- Head and Neck Surgery, Leuven, Belgium 

4 

UNIVERSITY HOSPITALS GASTHUISBERG, Pathology, Leuven, Belgium 

Purpose: With highly conformal radiotherapy (RT) techniques, accurate localization 

of head and neck squamous cell carcinoma (HNSCC) is crucial. 

This pilot study prospectively examined the use of diffusion-weighted (DW) 

magnetic resonance imaging (MRI) for nodal staging and its impact on RT 

planning. 

Materials: From June 2004 to April 2006, 22 patients with locally-advanced 

HNSCC received a contrast-enhanced computed tomography (CT) as well 

as an MRI scan prior to neck dissection surgery. MRI examinations consisted 

of both routine turbo spin-echo (TSE) sequences and DW sequences 

with a large range of b-values (0 to 1000 sec/mm). After topographic correlation, 

lymph nodes (LN) were evaluated microscopically with prekeratineimmunostaining. 

An optimal apparent diffusion coefficient (ADC) threshold 

for discriminating between malignant and benign LN was determined. A RT 

planning study was performed on these surgically treated patients. One set of 

target volumes was designed with conventional imaging (CT and TSE-MRI) 

guidance only, and another with the corresponding DW-MRI images. A third, 

reference set was contoured solely based on pathology results ("gold standard"). 

Results: Using an ADC threshold of 0.00094 mm/sec, a sensitivity of 89% 

and a specificity of 97% per LN was found for DW-MRI. The neck level staging 

sensitivity and specificity for DW-MRI was 94% and 97%, respectively. DW-


MRI correctly detected nodal disease in 4 patients considered N0 on conventional 

imaging and bilateral disease in 2 patients considered to have unilateral 

disease. Also, 2 patients considered to have nodal disease on conventional 

imaging were correctly downstaged to N0 by DW-MRI. Nodal staging 

agreement between imaging results and pathology findings was significantly 

stronger for DW-MRI (Kappa 0.97; 95% confidence interval (CI): 0.84 1.00) 

than for conventional imaging (Kappa 0.56; 95% CI: 0.16 0.96; p = 0.019 by 

McNemar’s testing). For both imaging modalities, the absolute differences in 

RT volumes with those obtained by pathology were calculated. Using an exact 

paired Wilcoxon test, the observed difference was significantly larger for 

conventional imaging compared to DW-MRI for nodal gross tumor volume (p 

= 0.0013) as well as for nodal clinical target volume (p = 0.034) delineation. 

The nodal gross target volume (GTV) was correctly changed in 68% (15/22) 

of patients based on DW-MRI. There was an increase in 12 patients of a 

mean 41% of the reference GTV, which would have received insufficient dose 

on conventional imaging alone. 

Conclusions: These findings suggest that DW-MRI is superior to conventional 

imaging for pre-RT nodal staging of HNSCC, with an important potential 

impact on organ-sparing and disease control. Confirmatory trials should 

be initiated, preferably in comparison with [ 18 F]-fluorodeoxyglucose (FDG) 

positron emission tomography (PET). 

463 oral 

IDENTIFICATION OF RADIORESISTANT AREAS WITHIN THE 

TUMOR USING FDG-PET-CT: WHERE DOES RADIOTHERAPY 

FAIL? 

G. Bosmans 1 , H. Aerts 1 , S. Petit 1 , C. Offermann 1 , A. Dekker 1 , P. Lambin 

1 , D. De Ruysscher 1 , A. van Baardwijk 1 

1 MAASTRICHT UNIVERSITY MEDICAL CENTRE (MUCM+), Department of 

Radiation Oncology (MAASTRO), GROW ? School for Oncology and Devel, 


Purpose: In recent years, it has become clear that tumors are not homogeneous, 

but heterogeneous, for biologic characteristics and radioresistance. 

Identification of radioresistance areas within the tumor is of great interest, for 

it may allow selective boosting of these zones. This study addressed the critical 

question whether the location of the residual disease after radiotherapy 

can be predicted based on FDG-PET imaging. This knowledge is crucial to 

design strategies to escalate or redistribute dose within the tumor based on 

FDG-PET imaging. 

Materials: 95 patients with inoperable NSCLC (stage I-III), treated with radical 

radiotherapy alone or with chemo-radiation were studied as part of two 

phase II trials (NCT00573040, NCT00572325). Two FDG-PET scans were 

available for each patient, one before start of radiotherapy (pre-scan) and 

one after radiotherapy (post-scan). Of these 95 patients, 32 showed residual 

disease on the post-radiotherapy scan from which 4 were excluded due 

to large deformation. The volume of residual disease was defined by the 

area with a Standardized Uptake Value (SUV) higher than the uptake in the 

aortic arch. The overlap fraction (OF) was defined as the overlap of several 

SUV threshold based auto-delineations (34-90% of the maximal SUV) on the 

pre-scan with the residual disease of the post-scan. 

Results: The residual disease was located almost completely (OF > 90%) 

within the contour of the original tumor (18 of the 28 patients analyzed so 

far), defined as the 34% threshold SUV contour, based on the source-tobackground 

ratio (van Baardwijk et al Int J Radiat Oncol Biol Phys 2007). As 

depicted in figure 1, on average (bold black line) the residual disease had 

an OF of more than 70% with the 50% SUV threshold of the pre-treatment 

PET scan. Due to the small volumes of the 70-90% SUV thresholds before 

therapy, the OFs with the residual disease were low. 

Conclusions: Residual disease within the primary tumor is not due to geographic 

miss. The location of residual disease largely corresponds with the 

original high uptake area before radiotherapy. Therefore, escalating dose to 

this specific area is likely to improve local control. Figure 1. Overlap Fractions 

of the residual disease on the post radiotherapy scan with the SUV threshold 

of the PET scan before radiotherapy. 

464 oral 

S 153 

TO DEVELOP A SEGMENTATION PROCESS THAT UTILIZES 

OPTIMIZED ANATOMICAL PLANES 

D. Low 1 , C. Abraham 1 , P. Parikh 1 , S. Mutic 1 , W. Thorstad 1 , L. Lu 2 , D. 

Khullar 1 , A. Apte 1 , J. Deasy 1 , T. Ju 2 

1 WASHINGTON UNIVERSITY, Radiation Oncology, Saint Louis, USA 

2 WASHINGTON UNIVERSITY, Computer Science, Saint Louis, USA 

Purpose: To develop a segmentation process that utilizes optimized anatomical 

planes. 

Materials: The segmentation process currently used in radiation therapy was 

developed within the historical limitations of computed tomography (CT) scanners 

and treatment planning systems; specifically the need to use relatively 

thick CT slices. With modern multi-slice CT scanners, sub-millimeter isotropic 

voxel imaging is available, so the bias inherent in the use of transverse slices 

can be examined. A central hypothesis of this study is that the segmentation 

of the CT scans, which are 3-dimensional scalar matrices, will require a) a 

quantitative evaluation of the spatial correspondence between the scalar field 

data and the segmentation boundary (contour) and b) this evaluation requires 

the presentation of two-dimensional slices (planar or curved) through the CT 

dataset. Hypothesis a) is based on the absolute registration requirement between 

the radiation beams and the structures and hypothesis b) is based on 

fundamental limitations of visualization of 3D scalar matrix datasets. Given 

these constraints, an investigation of the optimal location of contouring planes 

is being conducted. We propose orienting the planes using anatomical reference 

regions such as lymph node chains. We hypothesize that the results 

of this segmentation technique will be both more accurate and more efficient 

than the current transverse-based processes. In order to determine the number 

and orientation of contour planes required to accurately reconstruct structures, 

a structure library has been generated. For each structure, planes were 

positioned and the surface intersection with the planes defined a contour. The 

surface was generated based on these contours and compared against the 

original surface. The number and orientation of the intersecting planes was 

varied. 

Results: The segmentation tests were conducted on a prostate library and 

the accuracy of reconstruction using 3 mm transverse planes was compared 

against the oblique planes. In general, half as many oblique planes were 

required to match the accuracy of the transverse planes. 

Conclusions: We are proposing a novel approach to contouring that utilizes 

anatomically referenced oblique planes. This project requires the generation 

of an algorithm to generate a surface from oblique contours, the determination 

of the number of contours required to reconstruct typical structures in 

radiation therapy, and evidence that efficient and accurate navigation through 

the 3D dataset is possible. The first step has been accomplished and initial 

data from the second step indicates that fewer oblique contours are required. 

The final step is in preparation. If successful, the proposed process could 

revolutionize the methods with which radiation oncologists interact with the 

basic imaging datasets used for segmentation generation and evaluation. 

465 oral 

AUTOMATIC EVALUATION OF THE LOCAL UNCERTAINTY OF 

DISPLACEMENT VECTOR FIELDS RESULTING FROM A B-SPLINE 

DEFORMABLE REGISTRATION ALGORITHM 

M. Hub 1 , M. Kessler 2 , C. Karger 1 

1 

GERMAN CANCER RESEARCH CENTER (DKFZ), Department of Medical 

Physics, Heidelberg, Germany 

2 

UNIVERSITY OF MICHIGAN, Department of Radiation Oncology, Ann Arbor 

MI, USA


Purpose: We developed a method to distinguish image regions where a 

b-spline deformable registration algorithm performs accurately from areas 

where the registration is likely to be less accurate. 

Materials: After b-spline registration based on the SSD-metric, the resulting 

coefficients are input for the algorithm described here. If the result of a registration 

is well-defined the SSD should increase with any additional deformation. 

In any position where this is locally not the case, we can not distinguish 

whether the initial or the modified displacement vector is the better estimate. 

This ambiguity can be used to estimate the uncertainty of the registration. We 

calculate the local contribution to the global SSD metric from a small region 

around each voxel and evaluate its dependence on moderate and randomly 

performed variations of the b-spline coefficients. 400 small random modifications 

are applied to each b-spline coefficient. For each set of modified coefficients, 

the test image is deformed accordingly and the deviation between the 

resulting and the initial displacement is calculated for each direction in space 

and for each voxel. For each voxel and direction, the largest deviation (dmax) 

in any of the test deformations, for which the local SSD is smaller than or 

equal to the initial local SSD, is stored as a measure of the uncertainty. 

Results: An artificially deformed lung data set was used as reference and 

registered with its un-deformed version. We calculated the magnitude of the 

deviation between the ground truth and the estimated displacement vector for 

each voxel. This displacement is regarded as the local error of the registration. 

Fig. 1 shows that we have a smaller average registration error for the 

voxels with a dmax value below a threshold (well registered region) compared 

to averaging over all voxels. In addition, the algorithm was applied to a deformable 

phantom with internal markers of known displacement. In positions 

with large local errors in SI direction, large values for dmax,z. were obtained. 

Conclusions: The local sensitivity of a figure of merit in deformable alignment 

has the potential to divide an image into sub-regions which differ in 

the magnitude of their average registration error. This method has been successfully 

demonstrated with images from a deforming phantom and on clinical 

data with simulated deformations. 

466 oral 

MARGIN DESIGN FOR DEFORMING AND DIFFERENTIAL MOVING 

TARGET VOLUMES 

S. R. van Kranen 1 , M. van Herk 1 , J. J. Sonke 1 

1 NETHERLANDS CANCER INSTITUTE - ANTONI VAN LEEUWENHOEK 


Purpose: Image guided radiotherapy in combination with advanced registration 

techniques revealed substantial deforming and differential moving 

anatomy (multiple targets with different motion) for tumor sites such as headand-neck, 

rectum and lung. Classical recipes (e.g. M=2.5Σ+ 0.7σ), assume 

the target to be a single rigid object, which is clearly violated in the presence 

of such changes. The purpose of this study was to derive margins for 

differential moving targets and deformations. 

Materials: The framework of the classical margin recipe was extended by analyzing 

multiple points in space (differential motion) or on a spherical surface 

with deformations perpendicular to the surface. All points move with a Gaussian 

distribution with a constant standard deviation Σ and a single correlation 

r between the distributions which could be varied. By generating many possible 

instances the margin required to encompass all points for 90% of the 

instances was derived as a function of the number of points, r and Σ (Monte 

Carlo simulations). In this analysis, we focused on the effect of the systematic 

error as the random errors still blur the dose distribution and their effect 

for deforming and differential motion is unchanged compared to a single rigid 

object. 

Results: Complete target coverage for 90% of the population depended on 

the number of points and the their correlation, see figure 1. If points move 

with r=1, the solution for classical 90% coverage probability was retrieved, 

i.e. a margin of 2.5Σ for multiple targets and 1.3Σ for deformations (single 

sided 1D probability distribution). For the fully uncorrelated situation, margins 

depended on the number of points. For deformations 20 points results in a 

margin of 2.5Σ, 200 points in 3.2Σ. For a situation with multiple rigid targets, 

the margins required increased from 2.8Σ (2 targets) to 3.1Σ (5 targets). 

Conclusions: It is appealing to apply classical margins for deformations or 

differential moving anatomy but the results are incorrect for 2 reasons. First, 

target coverage is unaffected for surface-points moving inwards. Second, 

with more than one point the probability of having all points within classical 

margins simultaneously decreases. We expect that larger tumors need more 

points to describe observed deformations and margins will increase accordingly. 

Hypoxia and Vasculature 

467 oral 

IMPACT OF FRACTIONATED IRRADIATION ON TUMOR MICROEN- 

VIRONMENT IN HUMAN SQUAMOUS CELLS CARCINOMAS (HSCC) 

IN NUDE MICE 

A. Yaromina 1 , D. Zips 1 , H. Thames 2 , T. Kroeber 1 , A. Meinzer 1 , C. 

Petersen 3 , B. Beuthien-Baumann 4 , M. Baumann 5 

1 

UNIVERSITY OF TECHNOLOGY DRESDEN, MEDICAL FACULTY C.G. CARUS, 

Department of Radiation Oncology, OncoRay Radiation Research Center, 


2 

UNIVERSITY OF TEXAS M.D. ANDERSON CANCER CENTRE, Department 


3 

PRAXIS F. RADIOONKOLOGIE, Hamburg, Germany 

4 

PET-ZENTRUM FORSCHUNGSZENTRUM DRESDEN ROSSENDORF, Nuclear 

Medicine, Dresden, Germany 

5 

UNIVERSITY OF TECHNOLOGY DRESDEN, MEDICAL FACULTY C.G. CARUS, 

Radiation Oncology, Experimental Centre, OncoRay - Centre for Radiation 

Research, Dresden, Germany 

Purpose: To investigate whether changes in tumor microenvironment during 

fractionated irradiation correlate with the outcome of radiotherapy. The results 

are compared with changes in radiobiological hypoxic fraction of tumor stem 

cells (rHF) after fractionated irradiation.


Materials: UT-SCC-14 and FaDu hSCC were transplanted s.c. into the leg 

of nude mice. Tumors at 7 mm diameter were irradiated with 30 fractions 

in 6 weeks (variable total doses). To determine rHF after 15 2-Gy fractions, 

tumors were irradiated with graded single doses under ambient or clamp conditions. 

rHF was estimated using maximum likelihood models. rHF of unirradiated 

tumors was determined previously. Local tumor control was evaluated 

120 days after irradiation. Radiation response was quantified as dose 

required to cure 50% of tumors (TCD50). For histological evaluation, 11 unirradiated 

tumors and 9-12 tumors irradiated with 3, 5, 10, or 15 2-Gy fractions 

were excised after injection of pimonidazole and perfusion marker Hoechst. 

To detect tumor vasculature, an antibody against endothelium (CD31) was 

used. Relative hypoxic area within a viable tumor region (pHF), relative vascular 

area (RVA), fraction of perfused vessels (PF), and necrotic fraction (NF) 

were determined in 2-4 sections per tumor. 

Results: TCD50 after 30 fractions/6 weeks was 44Gy [95% CI 30;53] for UT- 

SCC-14 and 61Gy [56;68] for FaDu. The rHF increased after 15 fractions from 

22% to 56% (p=0.036) for UT-SCC-14 and from 40% to about 100% for FaDu. 

In UT-SCC-14, there were significant changes in pHF, RVA, and PF after irradiation 

with 5 fractions (compared with unirradiated tumors). pHF increased 

from 19% to 25% (p=0.036), RVA decreased from 2.2% to 1.9% (p=0.06), 

and PF decreased from 83% to 74% (p=0.04). NF increased throughout fractionated 

irradiation (p=0.0002). 

Conclusions: Impact on tumor microenvironment was most visible after 5 

fractions. There was an increase in hypoxic fraction at the same time as a decrease 

in tumor vascularisation and perfusion. The modest changes in histological 

parameters during irradiation however cannot explain the dramatic increase 

in rHF after 15 fractions. Whether these parameters measured during 

fractionated irradiation better correlate with radiotherapy outcome compared 

with pretreatment measurements requires histological evaluation of more tumor 

lines, which is ongoing and results on total of 3 tumor types will be included. 

Supported by DFG Ba1433/5-1 and in part by the 6th framework 

EU-project BioCare, proposal No505785. 

468 oral 

SERIAL [18]FAZA-PET IMAGING FOR CHANGES IN HYPOXIA DUR- 

ING / POST RADIOCHEMOTHERAPY AND IMPACT ON TREATMENT 

OUTCOME 

B. Röper 1 , R. Beck 2 , N. Andratschke 1 , A. Weber 2 , J. A. Lebschi 2 , J. M. 

Carlsen 2 , M. Picchio 3 , M. Souvatzoglou 2 , H. J. Machulla 4 , M. Piert 5 

1 

KLINIKUM RECHTS DER ISAR, TECHNICAL UNIVERSITY OF MUNICH, 

Department of Radiation Oncology, Muenchen, Germany 

2 


Department of Nuclear Medicine, Muenchen, Germany 

3 

SCIENTIFIC INSTITUTE SAN RAFFAELE, IBFM-CNR, Department of 

Nuclear Medicine, Milan, Italy 

4 

UNIVERSITY OF TÜBINGEN, Radiopharmazie, PET Zentrum, Tübingen, 

Germany 

5 

UNIVERSITY OF MICHIGAN, Nuclear Medicine, Ann Arbor MI, USA 

Purpose: To explore the changes in hypoxia under radiotherapy (RTx), 

hypoxia-directed chemotherapy (CTx) and combined radiochemotherapy 

(RCTx) in comparison with sham-treated tumours (NIL) in a mouse model by 

means of serial PET-imaging using the hypoxia tracer [18]F-fluoroazomycin 

arabinoside (FAZA). 

Materials: 85 EMT6 tumor bearing mice were subjected to serial FAZA-PET 

examinations in the context of conservative tumour treatment with RTx (36Gy 

total dose in fractions of 4.5Gy b.i.d), CTx (8 i.p.-injections of Tirapazamine 

14mg/kg, b.i.d.), RCTx or NIL. Tumour growth was investigated three times 

per week by volumetric ultrasonography (11MHz). Treatment was started at 

a median tumour volume of 70µl. Volumetric follow-up was continued until 

exceeding 500 µl or intercurrent death. PET examinations were scheduled 

before start of treatment and at least once during follow-up. FAZA-uptake was 

given as tumour-to-background ratio (TB-ratio). 

Results: 70 of 85 mice (17 or 18 in each treatment group) completed therapy 

and had at least one pre- and one posttherapeutic FAZA-PET. They accounted 

for 199 of all 220 PET scans performed of which 195 were evaluable 

(98%), consisting of 80 datasets at a median of 1 day before and 115 

at a median of 8 days after individual start of therapy. FAZA-uptake correlated 

with tumour volume in untreated tumors (correlation coefficient [CC] 

0.84). CTx alone did not alter this finding at all (CC=0.83) and RTx alone 

marginally (CC=0.76). Only combined treatment (RCTx) lead to changes in 

hypoxia less dependent on tumour volume (CC=0.57). Calculation of linear 

regression curves (x-axis: common logarithm of tumour volume at the date of 

PET-imaging, y-axis: FAZA-uptake) resulted in slopes of 1.54 for NIL, 1.94 for 

CTx, 1.33 for RTx and 0.90 for RCTx, respectively. Calculated absolute increase 

of more than 0.2 units in TB-ratio per day between last pretherapeutic 

and first posttherapeutic PET predicted rapid tumor growth (from 70 to 500ul 

within 16 days) with a specificity of 83% and a sensitivity of 50% (Chi-Square 

= 4.36, p80% of ROI 

(range 34% to 99%). However, in the majority of the tumours (45/55), there 

was a large (>95%) contribution of low signal intensity areas to this positive 

colocalisation. Colocalisation of high signal intensities was much less (mean: 

0.1%, range 0% to 22%).Sixty-five percent (36/55) of the tumours showed 

positive colocalisation between pEGFR-pAkt in >80% of the ROI (range 28% 

to 99%). Also here, this was mainly attributable to low signal intensity areas. 

No significant correlations were found between pEGFR-pimonidazole 

or pEGFR-pAkt colocalisation and clinical parameters such as tumour site or 

stage. 

Conclusions: The high percentage of ROI with positive colocalisation of 

pEGFR-pAkt provides evidence for the activation of the PI3-K/Akt - pathway 

by pEGFR in head and neck tumours. The positive colocalisation of pEGFRpimonidazole 

in low signal intensity areas suggests activation of EGFR under 

conditions of intermediate hypoxia but less so in severe hypoxia. 

470 oral 

TARGETING TRANSLATIONAL CONTROL PATHWAYS IN HYPOXIC 

CELLS SENSITIZES TUMORS TO IRRADIATION 

B. Wouters 1 , K. Rouschop 2 , L. Dubois 2 , T. van den Beucken 1 , K. 

Savelkouls 2 , P. Lambin 3 , M. Koritzinsky 1 

1 

ONTARIO CANCER INSTITUTE/PRINCESS MARGARET HOSPITAL, Toronto, 


2 

MAASTRICHT UNIVERSITY, Maastro, Maastricht, Netherlands 

3 

MAASTRO CLINIC, Radiotherapy, Maastricht, Netherlands 

Purpose: Hypoxia is a common feature of tumors that contributes to malignancy 

and treatment resistance. The basis for these effects derives in part 

from a transcriptional response mediated by the hypoxia inducible factor (HIF) 

family of transcription factors. In addition, we have shown that hypoxia influences 

mRNA translation by activation of the PERK kinase as part of the unfolded 

protein response (UPR) and by inhibition of the eIF4F complex which is 

controlled by the mammalian target of rapamycin (mTOR). Although several 

studies implicate important roles for HIF, PERK and mTOR in hypoxic adaptation, 

the potential of targeting these pathways to modify hypoxia and therapy 

response has not been addressed. To this end, we established a new tumor 

model that allows therapeutic evaluation of targeting these pathways within 

an identical genetic background. 

Materials: Cell lines were engineered to accept transgenes at a single genomic 

location encoding dominant negative or mir30 based RNAi targeting 

various components of these three hypoxic response pathways. To closely 

mimic the clinical situation, transgene expression is regulated by doxycycline 

such that tumors can be established with a wild type phenotype and subsequently 

induced to inactivate the pathway of interest. 

Results: In tissue culture, knockdown of HIF-1α resulted in decreased proliferation 

under hypoxic conditions, whereas interference with UPR and/or 

mTOR signaling had no proliferation defect. Conversely, cells defective 

in UPR activation (via expression of eIF2α(S51A) or over-expression of


GADD34) or mTOR-signaling (overexpression eIF4E) were significantly sensitized 

to hypoxia induced cell death, whereas HIF knockdown cells were not. 

In vivo, targeting the HIF, UPR or mTOR pathways after tumor establishment 

had little or no effect on overall tumor growth. However, targeting both the 

UPR and mTOR pathways resulted in a significant increase in tumor growth 

delay after radiation therapy in comparison to wild type tumors or tumors induced 

to inactivate HIF. 

Conclusions: Together these data suggest that pathways regulating translation 

play important roles in facilitating hypoxic cell survival and tumor radioresistance. 

471 oral 

NITRIC OXIDE SYNTHASE INHIBITION AND THE EFFECTS OF 

ITS COMBINATION WITH COMBRETASTATIN-A4-PHOSPHATE AND 

RADIOTHERAPY 

H. Mandeville 1 , P. Hoskin 1 , G. Lewis 2 , V. Prise 2 , M. Saunders 1 , G. Tozer 

3 , S. Hill 2 

1 

MOUNT VERNON HOSPITAL, Marie Curie Research Wing, Northwood 

Middlesex, United Kingdom 

2 

GRAY CANCER INSTITUTE, UNIVERSITY OF OXFORD, Northwood, 


3 

UNIVERSITY OF SHEFFIELD, Sheffield, United Kingdom 

Purpose: To investigate tumour growth delay using the nitric oxide synthase 

inhibitor, N(omega)-nitro-L-arginine (L-NNA) with combretastatin-A4phosphate 

(CA4P) and radiotherapy (RT). 

Materials: Murine adenocarcinomas NT (CaNT) in female CBA mice were 

used with geometric mean diameter (GMD) 5-6.5 mm. All treatment schedules 

were administered over a 2 week period. Schedules were as follows: 

L-NNA (Sigma-Aldrich Co. Ltd., UK) 1mg/ml in drinking water continuously, 

CA4P (Oxigene Inc., USA), 100 mg/ kg ip given on the 5th day of each week, 

CA4P 50mg/ kg ip 5 times a week given immediately after RT; L-NNA, CA4P 

and RT were given in all possible combinations with appropriate controls 

used. RT was delivered using 240 kV/ 15 mA X-rays, 40Gy in 8 fractions; 

4 daily fractions followed by a three day gap then a further 4 daily fractions. 

After treatment tumours were measured in 3 orthogonal diameters 2- 3 times 

a week. Tumour volumes were then calculated and normalised to allow comparison 

of mean growth curves for each group. The time taken for regrowth to 

3 times original volume was then calculated to allow statistical analysis using 

one-way ANOVA followed by Tukey-Kramer multiple comparisons testing. 

Results: Mean time to grow to 3 times the original tumour volume +/- 1SE, 

for the different treatments and combinations, are shown in the table. Both 

CA4P alone and L-NNA alone induced a significant tumour growth delay. 

Both schedules of CA4P combined with L-NNA significantly improved tumour 

growth delay compared to either treatment given alone. CA4P 100 mg/ kg 

given ip 24 hours after the final fraction of RT each week produced enhanced 

tumour growth delay but this effect was not seen with CA4P 50mg/kg given 

throughout the radiation course. The addition of L-NNA to RT +/- CA4P did 

not show any significant additional benefit. 

Conclusions: Results suggest that L-NNA enhances CA4P-induced tumour 

vascular disruption. Weekly CA4P significantly increased growth delay obtained 

with RT alone, suggesting efficacy of CA4P on irradiated or re-growing 

blood vessels. Daily CA4P and L-NNA in the drinking water were less effective 

than weekly CA4P in combination with RT and the combination of weekly 

CA4P and RT was not improved by the addition of L-NNA. This suggests that 

the benefit of adding a vascular-disrupting agent to radiotherapy is compromised 

if given throughout the course of radiation treatment, which could be 

due to induced hypoxia from vascular shut-down. Further scheduling studies 

are warranted to determine whether it is possible to exploit, in radiotherapy, 

the benefit of enhanced tumour vascular disruption obtained with the combination 

of L-NNA and CA4P. 

472 oral 

HYPOXIA INHIBITS DISULFIDE BOND FORMATION AND PROTEIN 

FOLDING IN THE ENDOPLASMIC RETICULUM 

M. Koritzinsky 1 , K. Rouschop 2 , T. van den Beucken 2 , I. Braakman 3 , B. 

Wouters 1 

1 

UNIVERSITY HEALTH NETWORK, Ontario Cancer Institute, Toronto, Canada 

2 

MAASTRICHT UNIVERSITY, Maastricht Radiation Oncology, Maastricht, 

Netherlands 

3 

UTRECHT UNIVERSITY, Department of Chemistry, Utrecht, Netherlands 

Purpose: Hypoxia activates cellular stress pathways that are consistent with 

the presence of endoplasmic reticulum (ER) stress. Here, we investigated 

the underlying mechanism responsible for hypoxia induced ER stress. We 

hypothesized that, like in yeast, molecular oxygen serves as the terminal electron 

acceptor during oxidative protein folding. We therefore predicted that lack 

of oxygen inhibits disulfide bond formation and protein folding in the ER. 

Materials: Using a pulse-chase assay, we characterized the maturation pathway 

of a model protein, influenza-hemagglutinin (Flu-HA), during hypoxia. We 

radioactively labeled Flu-HA with 35S-methionine during its synthesis and 

immunoprecipitated it 0-120 minutes following labeling. Flu-HA contains six 

intrachain disulfide bonds that are formed in a well-defined order following


its synthesis. We monitored the formation of these disulfide bonds on nonreducing 

SDS-PAGE gels. Flu-HA also undergoes several rounds of oligosaccharide 

modifications during maturation. We monitored sugar processing on 

reducing SDS-PAGE gels. 

Results: Hypoxia prevented the formation of disulfide bonds in Flu-HA. In 

consequence, Flu-HA could not undergo complex glycosylation in the Golgi. 

The inhibition of disulfide bond formation was reversible upon reoxygenation. 

In contrast, hypoxia did not affect co-translational N-linked glycosylation or 

modifications of these glycans in the ER. 

Conclusions: Hypoxia severely inhibits the formation of disulfide bonds in 

the ER. This has important implications for hypoxia induced secreted or membrane 

bound proteins which all mature in the ER. 

Motion and uncertainties 

473 oral 

MOTION-COMPENSATED CONE-BEAM CT FOR ACCURATE ON- 

LINE ASSESSMENT OF THE POSITION OF LUNG TUMORS 

S. Rit 1 , J. Wolthaus 1 , M. van Herk 1 , J. J. Sonke 1 



Purpose: Respiratory motion induces artifacts in cone-beam (CB) CT images 

of the thorax which can prevent an accurate localization of lung tumors 

at treatment time for patient positioning. Respiration-correlated reconstruction 

has been used to correct for this motion but only a subset of the CB 

projections is used to reconstruct each frame of the 4D CBCT image thus requiring 

a long acquisition time. We propose instead an online implementation 

of motion-compensated (MC) CBCT, i.e. the compensation of the respiratory 

motion during the reconstruction from all the CB projections using a prior 

estimation of a model of the respiratory motion. 

Materials: A model of the patient respiratory motion, represented by a 4D 

deformation vector field (DVF), was constructed from the 4D planning CT 

with deformable registration. The respiratory motion during the CB acquisition 

was derived from this model depending on the phase of a respiratory signal 

extracted from the X-ray images. The motion was compensated in the filteredbackprojection 

reconstruction by warping each backprojection according to 

the 4D DVF. The method was evaluated on 26 CBCT scans of 3 patients 

acquired on an Elekta Synergy with the two protocols used for static CBCT 

(1 min scan time) and 4D CBCT (4 min scan time). For each scan, three 

CBCT images were reconstructed: non-corrected, respiration-correlated and 

motion-compensated and tumor localization accuracy was evaluated with the 

4D CBCT image as a reference. 

Results: Visual observation of reconstructed MC-CBCT images showed that 

most of the respiratory motion artifacts were removed while preserving an 

image quality comparable to static CBCT, even for the 1 min protocol where 

4D CBCT is unusable due to strong view-aliasing artifacts. Compared to 

4D CBCT, the mean misalignment processed by the ROI registration of MC- 

CBCT images was 0.3 mm/0.5 mm with the 4 min/1 min protocol which is 

more accurate than non-corrected CBCT images for which it was 1.4 mm/1.2 

mm. The computational time was 3 hours for the estimation of the motion 

model (before the treatment fractions) and 230 s/67 s for the 4 min/1 min 

protocol for the reconstruction (concurrent with CB acquisition), providing thus 

a MC-CBCT image within a few seconds after the end of the acquisition. 

Conclusions: MC-CBCT corrects most of the respiratory motion artifacts as 

in 4D CBCT and is therefore an alternative solution to assess the position of 

lung tumors. Contrary to 4D CBCT, MC-CBCT uses all the CB projections to 

reconstruct a 3D CBCT which allows to reduce the acquisition time (from 4 

min to 1 min in our institution) while obtaining a higher image quality. 

474 oral 

S 157 

DELIVERY OUTCOME-DRIVEN ADAPTIVE REPLANNING STRAT- 

EGY FOR PATIENT DEFORMATION 

K. W. Jee 1 , R. Kashani 1 , A. Eisbruch 1 , J. Balter 1 , M. Kessler 1 , D. 

McShan 1 , R. Ten Haken 1 , B. Fraass 1 

1 UNIVERSITY OF MICHIGAN MEDICAL CENTER, Radiation Oncology, Ann 

Arbor, MI, USA 

Purpose: With increasing availability of imaging and dosimetric information 

during a treatment course, the original plan can be altered to tailor delivery 

outcomes or control them in the presence of patient geometry variations or 

delivery errors. In this study, an off-line re-planning framework based on a 

multivariate optimal control concept (called Model Predictive Control) is investigated 

for IMRT treatments. 

Materials: The use of a re-planning strategy is demonstrated for patients exhibiting 

large anatomical changes. A patient with squamous cell carcinoma is 

shown below as an example. Repeat Cone-beam CTs available at treatment 

session 18, 23, 28, and 33 were used to track the deforming patient geometry 

as well as their associated calculation points used for IMRT optimization. 

The accumulated dose-to-date was calculated after each session. This information 

was fed back to the optimization system, tracking and estimating the 

delivery outcomes projected at the end of the treatment course. Re-planning 

was triggered to restore the original treatment goals by a tolerance limit. A replanning 

was performed for multiple non-linear planning constrains and goals 

using a multi-criteria optimization technique (preemptive goal programming). 

Results: With the adaptation of the treatment plan to the patient-specific 

anatomical changes, the plan delivery outcomes (particularly high priority 

goals) could be improved significantly in terms of accuracy and robustness 

to those changes. Results from the example case show changes in the 

predicted outcomes due to the anatomical deformation at four measurement 

points. Re-planning was triggered at the time when the first cone-beam data 

were available in order to account for deformed target volumes. A single replanning 

successfully restored the original goal levels for the primary target 

and high risk nodal volumes (e.g., the minimum PTV doses shown in solid 

lines) while reducing doses to the critical organs (e.g., the contralateral paratoid 

mean dose and the maximum cord dose), thus avoiding under dosing the 

targets which would have occurred without adaptation (shown in dotted lines). 

The timing of the most significant change (at least from this case) indicates 

that frequent patient model updates early in treatment may be most critical to 

plan adaptation. 

Conclusions: A re-planning framework driven by multiple delivery outcomes 

facilitates direct prediction and control of consequences brought by newly 

available patient models or treatment errors. Explicit handling of planning 

constraints allows intuitive tradeoffs among planning goals with different priorities 

at re-planning. Incorporation of dose-to-date at a given treatment session 

promotes accurate estimation of delivery outcomes allowing intuitive allocation 

of re-planning and QA resources as the fractionated treatment proceeds 

over time. Supported by NIHP01CA59827


475 oral 

A PRACTICAL METHOD TO DEAL WITH DIFFERENTIAL MOTION 

OF TARGET AND OAR DURING IMAGE GUIDED RADIOTHERAPY 

M. van Herk 1 , J. Belderbos 1 , E. Damen 1 , P. Remeijer 1 , J. J. Sonke 1 

1 THE NETHERLANDS CANCER INSTITUTE / ANTONI VAN LEEUWENHOEK 


Purpose: Current image guidance (IGRT) systems provide efficient on-line 

correction of the target position. Significant motion, however, may occur 

between the target and organs-at-risk (OARs), for instance for lung tumors 

(baseline shifts). In that case, proper positioning of the target may lead to 

overdosage of an OAR (e.g., the spinal cord). The purpose of this work is 

to devise a practical IGRT system that can deal with such differential motion, 

and to implement it for hypofractionated RT of lung cancer. 

Materials: During treatment planning, OARs were delineated and expanded 

by 1 cm to validate that differential motion of up to 1 cm could be safely 

corrected during treatment delivery without violating OAR dose constraints. 

In some cases a smaller expansion was required to reach an acceptable 

plan. The IGRT system is equipped with two regions of interest (ROIs) for 

registration. One is placed on the spinal column, while the other is placed 

around the target. Image registration is performed for both ROIs separately 

providing separate setup error data of OAR and target. Prior to determining 

the required table shift (typically the target registration without rotations), the 

software checks the proposed correction against predefined limits for both 

ROIs. The limit for the spinal column registration is set to the OAR expansion, 

while the limit for the target registration is set to the PTV margin (e.g., 

7 mm). When during IGRT the correction would move the high dose region 

outside limits towards the OAR, a warning message is generated. In a separate 

review procedure, the operator must then "fade" between correct target 

and OAR positioning to reach a compromise where both ROIs are within limits. 

The system has been applied in 86 patients with peripheral lung tumors 

treated with 3 fractions of 18 Gy. 

Results: In 10 out of 86 patients, the proximity of the tumor and OAR required 

PRV expansions of less than 1 cm. In 6 of these patients and 2 others, a 

compromise had to be made because the baseline shift was in the direction 

of the OAR during one or more fractions. In all cases, it was possible to find 

a correction that satisfied both target and OAR constraints. 

Conclusions: Especially in hypofractionated radiotherapy of lung tumors, differential 

motion of tumor and OAR may lead to serious overdosages when 

OARs are not considered in the IGRT procedure. We therefore developed 

and implemented a practical IGRT system to deal with this problem. 

476 oral 

FULL DOSIMETRIC EVALUATION OF THE IMPACT OF ORGAN 

DEFORMATION, ROTATION AND RESIDUE POSITIONING ERRORS 

IN PROSTATE AND SEMINAL VESICLE IRRADIATION 

T. Mutanga 1 , C. de Boer 1 , G. van der Wielen 2 , L. Incrocci 2 , B. Heijmen 1 

1 ERASMUS MC - DANIEL DEN HOED ONCOLOGY CENTER, Radiation 

Oncology, Division of Medical Physics, Rotterdam, Netherlands 

2 ERASMUS MC - DANIEL DEN HOED ONCOLOGY CENTER, Radiation 

Oncology, Rotterdam, Netherlands 

Purpose: We apply stereographic targeting (SGT) for accurate on-line 

prostate positioning on fiducial markers (Mutanga IJROBP 2008). SGT results 

in residue translation errors that are small compared to the dose gradients 

as well as compared to the residue rotation and deformation errors at 

the seminal vesicles (SV) and rectum. In this case, standard margin recipes 

(weighted combination of systematic and random error magnitudes) are of 

limited applicability. To derive appropriate margins, we therefore developed 

a system that rigorously determines the influence of all known geometric uncertainties 

on delivered dose. 

Materials: In a repeat CT scan study, rotation and deformation errors after 

SGT translation corrections were derived for prostate, rectum and SV using 

non-rigid registration (v.d. Wielen, IJROBP submitted). We used these results 

in our current study for 10 patients with a dose of 78 Gy prescribed to 

the prostate and entire SV volume (CTV). IMRT treatment plans were prepared 

(XiO, CMS) for a range of CTV-PTV margins for both the prostate and 

the SV (95% isodose encompassing the PTV). The impact of residue targeting 

errors was calculated by tracking moving voxels inside the planned dose 

distribution. This voxel motion was simulated according to known systematic 

and random error distributions from (1) rotations and deformations, (2) SGT 

residue errors and (3) intrafraction motions. For each patient, the statistical 

distribution of dose-volume parameters over simulated treatment courses 

was determined together with the average value over all treatment courses, 

appropriately separating the influence of systematic and random errors. 

Results: For 4 mm margin around the prostate and 7 mm around the SV, 

simulated actual dose coverage was still adequate. If V95% is the volume 

receiving at least 95% of the prescribed dose, then the change in expected 

V95% compared to planned V95% was 0% for the prostate in studied patients. 

For the SV, the corresponding V95% change was 0.1± 0.3%. For 

the rectum, V50Gy and V70Gy changed by 2.8±2% respectively 0.5±3% 

relative to treatment plan, mainly due to organ deformation. 

Conclusions: We have developed a system for margin optimization and validation 

in the presence of rotations and deformations. When applied to realistic 

dose distributions for SGT prostate treatments, we found that prostate 

margins of 4 mm and SV margins of 7 mm were adequate. Currently we 

extend our study by including more patients and TCP/NTCP analysis. 

477 oral 

A METHOD TO ESTIMATE MEAN TUMOR POSITION, TUMOR 

MOTION AND THE TUMOR TRAJECTORY FROM CONE-BEAM CT 

PROJECTIONS FOR PROSTATE IGRT APPLICATIONS 

P. R. Poulsen 1 2 , B. Cho 2 , K. Langen 3 , P. Kupelian 3 , P. Keall 4 

1 

AARHUS UNIVERSITY HOSPITAL, Department of Medical Physics and 


2 

STANFORD UNIVERSITY, Department of Radiation Oncology, Stanford, 

USA 

3 

MD ANDERSON CANCER CENTER ORLANDO, Department of Radiation 

Oncology, Orlando, FL, USA 

4 

STANFORD UNIVERSITY, Department of Radiaiton oncology, Stanford, USA 

Purpose: Cone-beam CT (CBCT) is currently used to create volumetric images 

prior to radiotherapy treatment. However, with radioopaque markers the 

CBCT projection data can provide much richer information. The aim of this 

work was to develop a probability based method for estimation of the mean 

tumor position, amount of tumor motion, and the tumor trajectory in 3D based 

on CBCT projections, and to investigate this method for prostate radiotherapy. 

Materials: CBCT acquisition was simulated for 536 prostate trajectories (17 

patients) recorded with electromagnetic transponders. Each track was divided 

into segments of 60 seconds (5261 segments in total) for which CBCT 

was simulated by projecting the 3D position onto a flat panel detector that 

rotated 360 degrees clockwise in 60 seconds. An imaging frequency of 10 

Hz was assumed, resulting in 600 projections per simulated scan. The mean 

and standard deviation of the tumor position and the AP-CC motion correlation 

were determined with maximum likelihood estimation (MLE) based on 

the projection data, assuming a Gaussian motion distribution. The unknown 

position along the imager axis was estimated for each projection as the expectation 

value determined by the MLE method. Transformation of the estimated 

3D position from imager coordinates to patient coordinates provided 

the estimated trajectory, which was then compared with the actual trajectory. 

The method was experimentally investigated by acquiring a CBCT scan of 

a 3D motion stage with a phantom that reproduced a patient-measured trajectory 

with large motion (Fig 1). The position of a marker in the phantom 

was extracted from the projections and used to estimate the trajectory by this 

method. 

Results: The root-mean-square (rms) and maximum 3D error for the mean 

prostate position was 0.04 mm and 0.92 mm, respectively. The standard 

deviation of the prostate position was determined with an rms (and maximum) 

error of 0.04 (0.63) mm (LR), 0.001 (0.07) mm (CC), and 0.05 (1.23) mm (AP). 

The trajectories were estimated with a mean and maximum rms 3D error of 

0.18 and 1.98 mm. The estimated trajectory from the experimental study was 

very close to that from the simulation, and as seen in Fig. 1 it was in good 

agreement with the actual trajectory of the motion stage. 

Conclusions: A method for accurate estimation of the mean tumor position, 

tumor motion and the tumor trajectory of the prostate from CBCT projections 

has been developed.


478 oral 

RESIDUAL SEMINAL VESICLE MOTION IN MARKER BASED IGRT 

FOR PROSTATE CANCER 

M. Smitsmans 1 , J. de Bois 1 , J. J. Sonke 1 , J. Lebesque 1 , D. Jaffray 2 , M. 

van Herk 1 

1 NKI-AVL, Radiation Oncology, Amsterdam, Netherlands 

2 PMH, Radiation Physics, Toronto, Canada 

Purpose: To account for prostate and seminal vesicle (SV) motion large 

margins are needed (mostly 10 mm is used). With current developments 

in image-guided radiotherapy (IGRT), prostate treatments become more accurate 

and margins can potentially be reduced. However, it is not known how 

much the SV move independently of the prostate gland, which is important 

when the SV are part of the target volume and marker based IGRT is used. It 

is the purpose of this study to determine residual motion of individual seminal 

vesicles and the corresponding safety margins for marker based IGRT. 

Materials: Cone-beam CT (CBCT) data, acquired at PMH, of 13 prostate 

cancer patients (297 CBCTs) with implanted markers were used. SV motion 

was determined with respect to marker registration with and without rotations 

incorporated (i.e., assuming that perfect correction is possible). The SV were 

individually registered (with help of regions of interest) using grey value information 

in the transverse plane using in-house developed software, only LR 

and AP translations (TLR and TAP) were assessed, assuming adequate coverage 

along the length of the SV. Subsequently, registrations were visually 

assessed and failures were corrected manually. Margins (M) were calculated 

using the 2.5 SIGMA + 0.7 sigma margin recipe. 

Results: The success rate of SV registration was very high: around 98% 

for both vesicles. Motion of both SV is comparable as well (Table 1). After 

correction for translation based on marker positions the SV motion is 2.8 mm 

SD in the LR direction and 4.1 mm SD in the AP direction. Correction for 

rotations of the markers (which were quite large: around 5 dg SD around the 

LR axis) did not reduce residual SV motion. 

Conclusions: Our data shows that margins for residual motion of the SV in 

marker based IGRT should be generous: 9 mm in AP direction and 6 mm in 

LR direction. Correction for rotations derived from implanted markers hardly 

reduces the SV motion, suggesting deformation of the SV with respect to the 

prostate gland that is not captured by the marker position. For those patients 

where the SV are part of the target volume, soft tissue based image-guidance 

methods may therefore be beneficial. 

Clinical dose measurements 

479 oral 

S 159 

2D IN-VIVO VERIFICATION IN CLINICAL ROUTINE USING EPID 

DOSIMETRY: CLINICAL EXPERIENCE WITH MORE THAN 2000 

PATIENTS 

S. Nysten 1 , W. van Elmpt 1 , B. Mijnheer 1 , L. Persoon 1 , P. Lambin 1 , A. 

Dekker 1 

1 UNIVERSITY HOSPITAL MAASTRICHT, Department of Radiation Oncology 

(MAASTRO), GROW, Maastricht, Netherlands 

Purpose: Electronic Portal Imaging Devices (EPIDs) are usually applied for 

patient set-up verification and detection of organ motion in clinical routine. Another 

application is the use of EPIDs for dosimetric verification of a treatment. 

However, only few departments use dosimetric EPID methods in clinical routine 

for large scale patient treatment verification. We have implemented 2D 

EPID dosimetry clinically based on in-house developed methods and apply 

this to all our patients treated with a curative intent. 

Materials: Six linear accelerators (Siemens Oncor) have been used, 

equipped with an amorphous silicon (a-Si) flat panel portal imager (Siemens 

OptiVue 500/1000/1000 ST) calibrated for portal dosimetry. Pre-treatment 

and in-vivo dosimetric verification procedures are applied comparing the 

measured 2D portal dose distribution with a predicted reference 2D portal 

dose image at the EPID plane. Measured and predicted portal dose distributions 

are compared using the gamma evaluation method. We have implemented 

this in a fully automatic way, with automatic flagging of gamma 

images that require evaluation by a medical physicist. 

Results: In the period between December 2006 and January 2008, up to 

2000 patients were enrolled in the in-vivo dosimetry program and more than 

10.000 treatment fields were verified. For breast, the most common cause of 

gamma differences was due to patient set-up: large dose differences occur 

due to the high gradient in thickness around the breast. For the lungs, common 

differences were found in the lateral beams and around the diaphragm 

related to breathing. The head-and-neck group showed differences due to 

changes in anatomy, patient position and used fixation aids. In the pelvic region, 

the most frequent cause of differences was due to rectum and bladder 

filling. Sometimes large individual patient errors were detected and corrected, 

e.g. attenuation of the treatment beam by the arm of a patient, large setup 

errors, erroneous density corrections in the TPS and an incomplete field-ofview 

of the planning CT. 

Conclusions: The described clinical procedures and physical methods have 

been clinically applied to all our patients treated with a curative intent for more 

than one year now. Based on these results, we have not only a fast way of 

monitoring the dosimetric accuracy of a treatment but also several errors have 

been detected and corrected. Therefore, we think that in future a standard 2D 

EPID dosimetry program for both pre-treatment and in-vivo verification of patient 

treatments is strongly required and currently feasible in clinical practice. 

480 oral 

CAN BRACHYTHERAPY ERRORS AND ACCIDENTS BE IDENTIFIED 

BY USING ONLINE IN VIVO TIME-RESOLVED LUMINESCENCE 

DOSIMETRY? 

C. Andersen 1 , S. Nielsen 2 , J. C. Lindegaard 3 , K. Tanderup 2 

1 

RISØ NATIONAL LABORATORY FOR SUSTAINABLE ENERGY, TECHNICAL 

UNIVERSITY OF DENMARK, Department of Radiation Research, Roskillde, 

Denmark 

2 


C, Denmark 

3 


Denmark 

Purpose: The prime objective of in vivo dosimetry in radiotherapy is to test if 

the dose delivery is carried out in accordance with the treatment plan. Significant 

discrepancies between measurements and plan are indicators of errors,


and it is the hypothesis of this work that online dose verification (in particular 

based on time-resolved measurements) can help to prevent dose delivery 

accidents in brachytherapy resulting from, for example, applicator reconstruction 

errors, interchanged guide tubes or afterloader malfunctions. 

Materials: We used a newly developed luminescence dosimetry system for 

in vivo measurements in a cervix cancer patient undergoing pulsed dose rate 

brachytherapy (Varian GammaMed Plus with Ir-192). The treatment comprised 

20 pulses (1 pulse/h) delivered by a combined intracavitary/interstitial 

applicator using a tandem ring system together with four needles with a total 

of 32 dwell positions. A dosimeter probe was placed in a brachy needle 

directly in the tumor region, and both radioluminescence and optically stimulated 

luminescence were recorded using a thin optical fiber cable between 

the dosimeter crystal and the optical readout instrumentation. 

Results: The time-resolved measurements (see figure) were essentially 

identical from pulse to pulse (0.5% relative standard deviation for the ~1 Gy 

dose per pulse), and the measurements were in excellent agreement with 

the expected values from the treatment planning system (i.e. within the experimental 

uncertainty) for all individual applicators and dwell positions. To 

test the ability of the method to detect errors, we systematically modified the 

treatment plan 80 times to simulate that any two guide tubes had been interchanged 

(see example in figure) or that one of the applicators had been 

offset by +/- 1 to 7 mm compared with its true position. 

Conclusions: It was found for this patient that we could detect (i) the interchange 

of any two guide tubes in 9 out of 10 cases, and (ii) the imposed 

applicator reconstruction errors larger than 6 mm in more than 50% of the investigated 

cases. The time-resolved dose-rate measurements (1 s time resolution) 

were found to be a significantly better indicator for errors than the timeintegrated 

doses. The time-resolved measurements furthermore provided a 

good way to visualize the progression and stability of the treatment. The findings 

from this study may be applicable also for brachy dosimetry based on 

diodes or other measurement techniques. 

481 oral 

3D DOSE VERIFICATION FOR LUNG CANCER TREATMENTS BY IN 

AQUA VIVO EPID DOSIMETRY 

M. Wendling 1 , L. McDermott 1 , A. Mans 1 , J. J. Sonke 1 , M. van Herk 1 , B. 

Mijnheer 1 



Purpose: In our hospital we implemented in vivo EPID dosimetry for almost 

all high-energy photon treatments of cancer with curative intent. Due to the 

large tissue inhomogeneities, lung cancer treatments were initially excluded 

from this dose verification method. The aim of this study was to test a new 

method, in aqua vivo EPID dosimetry, for fast absolute dose verification in 3D 

for lung cancer during actual patient treatment. 

Materials: Our current back-projection dose-reconstruction algorithm uses 

water-based scatter-correction kernels and does therefore not account for 

tissue inhomogeneities. For in aqua vivo dosimetry, the dose was reconstructed 

in the patient as if the patient would have consisted entirely of water. 

Therefore, every EPID transmission image was first corrected with a transmission 

conversion image, TCI, that was calculated for each gantry angle 

based on the planning CT scan (see Figure). Then the 3D dose distributions 

were reconstructed for each beam and summed to obtain the total 3D dose 

distribution. Comparison was made against the dose distribution calculated 

with the treatment planning system (TPS), where for this purpose the inhomogeneity 

correction was switched off. 3D dose distributions from the EPID 

and TPS were compared using 3D γ evaluation, applying criteria of 3% of the 

isocentre dose and 3 mm. Ten clinical lung cancer treatments with 6 and 10 

MV photons were investigated in aqua vivo (one fraction each). 

Results: The agreement between 3D EPID-based in aqua vivo dose distributions 

and the in aqua plans was very good. The ratio of the isocentre dose 

values of the in aqua vivo EPID dose and the in aqua plan was on average 

1.00 (0.02 SD). The region within the 50% isodose surface (relative to the 

isocentre dose) was statistically analysed. On average, 97% of points were 

within agreement (2.5% SD). The patient-averaged γmean was 0.39 (0.05 

SD). γ1% ("nearly the maximum") was on average 1.09 (0.25 SD). 

Conclusions: By using in aqua vivo EPID dosimetry, dose verification for 

lung cancer patients during the actual treatment is possible, except for the 

tissue inhomogeneity correction of the TPS. The method is accurate within γ 

criteria of 3% and 3 mm. As the verification is performed during the actual 

patient treatment and is based on patient-transmission images, it is sensitive 

to linac output variations, patient anatomy changes and patient shifts, which 

are all important for the actual delivered patient dose. This method has been 

implemented clinically. 

482 oral 

A METHOD TO PERFORM 3D IN VIVO DOSIMETRY USING MV 

CONE-BEAM CT AND EPID DOSIMETRY: FROM PLANNED TO 

MEASURED DOSE DISTRIBUTION 

W. van Elmpt 1 , S. Nijsten 1 , S. Petit 1 , B. Mijnheer 1 , P. Lambin 1 , A. Dekker 

1 



Purpose: A method has been developed to verify in vivo the 3D dose distribution 

delivered to patients based on measurements during treatment and 

on-line imaging. This method is completely independent of the treatment 

planning procedure. 

Materials: Patient anatomy is imaged using on-line low-dose (8 or 15 

MU) MV cone-beam CT data acquired with a commercially available linac 

(Siemens Oncor) prior or after treatment. The MV cone-beam CT images are 

corrected for cupping artifacts and converted into an electron density distribution 

that is used for dose calculation. Energy fluence exiting the linear accelerator 

is measured from transit dose EPID images acquired behind the patient 

during treatment using a calibrated a-Si EPID (Siemens OptiVue 1000). The 

patient-scattered dose is subtracted from the images and the energy fluence 

is extracted. This energy fluence is back-projected through the cone-beam 

CT scan and used as input for a 3D dose calculation using Monte Carlo 

simulations inside the cone-beam CT scan. The method has been tested 

for both homogeneous and inhomogeneous phantoms using conformal and 

IMRT treatment fields. 3D reconstructed dose distributions have been compared 

with planned dose distributions using a gamma evaluation (3%/3mm) 

in coronal, sagittal and transversal planes through the isocenter. 

Results: The 3D reconstructed dose distribution inside the MV cone-beam 

CT scan of a 4-field box treatment delivered to a cubic phantom showed excellent 

agreement with the planned dose distribution; more than 95% of the 

points in all planes had a gamma


transversal plane, respectively. A 5 field conformal treatment delivered to an 

inhomogeneous phantom consisting of a layer of low-density cork material, 

resulted in 98%, 94% and 99% of the points having gamma values


Symposium 

GENEPI LOW RT 

485 speaker 

INTRODUCTION TO GENEPI-LOWRT 

P. O’Neill 1 

1 UNIVERSITY OF OXFORD, Radiation Oncology and Biology, Oxford, United 

Kingdom 

Although recent advances in radiation delivery have significantly reduced the 

risk and severity of skin fibrosis, ~5-10% of patients receiving radiotherapy 

still suffer from normal tissue damage which seriously affects quality of life. 

Attempts to link normal tissue responses in patients and various phenotypical 

cell and molecular responses to high (>2.0 Gy) in vitro doses have generally 

been unsuccessful. Potentially, the high doses used previously could 

be masking a low dose effect. Furthermore, the pattern of gene expression 

induced by low dose radiation is very different from that seen at high doses. 

The GENEPI-lowRT project aims therefore to explore links between the development 

of severe, normal tissue complications following radiotherapy with 

various phenotypical responses and genetic pathways induced at low radiation 

doses. The project comprises 7 European clinical and basic science 

laboratories who will address whether changes in genetic and functional responses 

induced at low doses in either fibroblasts or T-cells derived from 

breast cancer patients correlate with the severity of patients’ normal tissue 

responses. Linking the GENEPI database (www.genepi-estro.org) with the 

levels of genetic changes induced at low dose provides an ideal opportunity 

to address whether genetic differences between individuals are associated 

with the development of severe, normal tissue complications The knowledge 

obtained from this combination of approaches will help assess if low dose 

effects can be used to quantify non-cancer health risks and identify potential 

genetic components of occupational, environmental and medical exposure to 

radiation. Funded by EU Sixth Framework Programme (FI6R-036452). 

486 speaker 

THE LYMPHOCYTE RESPONSE TO LOW AND HIGH DOSE IONIZ- 

ING RADIATION MEASURED BY GENE 

M. Giphart-Gassler 1 

1 LEIDEN UNIVERSITY MEDICAL CENTER, Leiden, Netherlands 

Radiation is an effective anti-cancer therapy but leads to severe late radiation 

toxicity in 5%10% of patients. These late effects limit the dose of radiotherapy. 

We postulate that variation in the incidence and severity of late complications 

is at least partly determined by intrinsic genetic differences between individuals. 

Such variation might be reflected by a difference in genetically regulated 

responses to radiation such as transcription. Our ultimate goal is to predict 

the severity of normal tissue damage after radiotherapy by transcription profiling. 

Assuming that genetic differences between individuals affect the transcriptional 

response to radiation of all cells, we have chosen T-lymphocytes as 

a surrogate tissue. We have determined the differences in gene expression 

after 2Gy in lymphocytes of patients treated for prostate cancer. This difference 

was used to discriminate between patients with severe late radiation 

toxicity from patients without complications following radiotherapy. By using 

a random cross validation strategy, a gene expression profile (classifier) was 

found that correctly classified 63% of the patients. A better performance was 

obtained by taking functional gene sets based on gene ontology for classification. 

Although the results were promising additional studies are needed, 

also because less correct classification was obtained of patients in an independent 

validation set. Classical cellular responses to in vitro radiation at 

a dose of 2Gy are dominated by cell killing and a p53-dependent transcriptional 

response. Interestingly, the most prominent radiation-responsive genes 

do not separate patients groups differing in late radiation toxicity. We propose 

that late radiation toxicity reflects more the sub-lethal effects of radiation in 

normal tissue. Therefore, we hypothesize in the Genepi-lowRT program that 

in vitro irradiation with low dose ≤100mGy evokes a transcriptional response 

that more closely relates to the late complications of radiotherapy. We intend 

to identify by microarray analysis, genes or gene sets which response after 

low dose radiation can discriminate between breast cancer patients from the 

Genepi cohort that differ in normal tissue toxicity. As a first step towards this 

goal, we determined gene expression patterns of T-lymphocytes from two 

control individuals after radiation with a range of low doses to identify lowdose 

specific pathways and dose response relationships. 

487 speaker 

STATISTICAL PROCESSING OF DNA MICROARRAY DATA: DETECT- 

ING SUBTLE CHANGES OF GENE 

J. Polanska 1 , H. Vrieling 2 , M. Giphart-Gassler 2 , A. Polanski 3 

1 

THE SILESIAN UNIVERSITY OF TECHNOLOGY, Systems Engineering, 


2 

LEIDEN UNIVERSITY MEDICAL CENTER (LUMC), Department of Toxicoge- 

netics, Leiden, Netherlands 

3 THE SILESIAN UNIVERSITY OF TECHNOLOGY, Institute of Informatics, 


Objectives: For some DNA microarray datasets, standard methods of gene 

expression profile analyses fail to provide statistically significant conclusions, 

yet there is evidence that these datasets might potentially lead to discovering 

interesting genetic mechanisms. An example of such datasets are the 

results of experiments related to low dose irradiation which contain only subtle 

differential expressions and therefore need special methods of analyses. 

In the presentation we overview methods of tuning methodologies of DNA 

data analyses to the problem of detection of subtle (low level) differences and 

signals in DNA microarray data. The results are based on the analysis of 

existing DNA microarray datasets related to sensitivity of patients and cells to 

irradiation. 

Methods: We studied several possible hypotheses concerning developing 

procedures for detecting low level signals and/or differences in DNA microarray 

data. These hypotheses concerned different levels of DNA microarray 

data processing: (i) the level of probes and cells and the level of DNA microarray 

data quality control, (ii) the level of annotations of genes corresponding to 

probes, (iii) the level of signal processing and classification algorithms. In the 

research we have composed and verified algorithms of different structures, 

based on the analyzed datasets. 

Results and Conclusions: The methodology for verification of the efficiency 

of different approaches was based on comparing predictive powers of classifiers 

with the use of multiple random validation tests. We observed that introducing 

various changes to constructions of classifiers, such as introducing 

rules of selections for genes, selecting genes by using quality control procedures 

or fitting classifiers to hypotheses concerning probability distributions of 

expression signals, may lead to differences of predictive powers of classifiers 

of the order of 10-20% of errors in the verification step. 

Acknowledgment: This work was supported by EURATOM project FI6R- 

036452 GENEPI-lowRT.

WEDNESDAY, SEPTEMBER 17, 2008 AWARD LECTURE 

Award lecture 

Varian/Fowler/Accuray 

488 oral 

IN-VIVO DOSIMETRY IN THE URETHRA AFTER INTERSTITIAL 

PROSTATE IRRADIATION. 

E. Bloemen- van Gurp 1 , B. Haanstra 1 , L. Murrer 1 , F. van Gils 1 , R. Pijls 1 , 

A. Dekker 1 , B. Mijnheer 1 , P. Lambin 1 


Purpose: In-vivo dosimetry in brachytherapy is a challenge due to the high 

dose gradients and the low photon energies involved. We present the results 

of a phantom and patient study to validate the micro-MOSFET for dose 

verification after permanent 125I implants and to evaluate the detector under 

clinical use in order to determine the dose in the urethra after the implant. 

Materials: Phantom measurements were performed to investigate the sensitivity 

of the micro-MOSFET under varying conditions. A reference measurement 

was performed to simulate the clinical situation using a clinical plan and 

a custom-made phantom. Measured and calculated dose values were compared. 

Patient measurements were performed in 17 patients, directly after the 

implant procedure using a high sensitive linear 5ive array (TN-502LA) positioned 

in the urine catheter. The in-vivo dose values were extrapolated to the 

total dose at these positions, using the known half-life time of the 125I, and 

the results were compared to the calculated dose values at these positions 

using the TPS. 

Results: A temperature correction of 11%, the deviation between calibration 

temperature and patient temperature, was implemented. Also a correction 

for the attenuation caused by the catheter was used. Patient in-vivo measurements 

demonstrated a mean deviation of -5.6%±17.6%. A deviation 

of -1.1%±9.9% (1SD) was observed in the higher dose region (>100 Gy). 

The larger deviations in the regions at distance from the seeds (low dose) 

are mostly due to the larger distance between the detector and the seeds 

resulting in increasing influence of inhomogeneities, which is not calculated 

accurately by the TPS. The global deviation, expressing the dose relative to 

the highest dose, is however a better way to express the dose in the low dose 

region (figure 2), resulting in a mean deviation of -4.8% ±11% (1SD). 

Conclusions: MOSFETs are potentially suitable for in-vivo dosimetry purposes 

after interstitial prostate implantation and can attribute considerably to 

the overall quality assurance of permanent 125I prostate implants. The high 

dose region is accurate enough to guard the dose to the urethra (~200gy). 

For adequate interpretation some factors still have to be investigated such as 

the influence of in homogeneity correction and inter-seed attenuation in the 

low dose region. 

489 oral 

CONSEQUENCES OF INTERMITTENT HYPOXIA ON THE RADIO- 

RESISTANCE OF THE VASCULAR AND THE TUMOR CELL 

COMPARTMENTS. 

P. Martinive 1 , F. Defresne 2 , C. Bouzin 2 , V. Grégoire 3 , C. Michiels 4 , O. 

Feron 2 

1 

ULG, Radiotherapy, Liège, Belgium 

2 

UCL, Unit of Pharmacology and Therapeutics, Brussels, Belgium 

3 

UCL, Center for Molecular and Experimental Radiotherapy, Brussels, 

Belgium 

4 

FUNDP, Laboratory of Biochemistry and Cellular Biology, Namur, Belgium 

Purpose: Hypoxia is a common feature in tumors associated with an increased 

resistance of tumor cells to therapies. Perfusion-limited or intermittent 

hypoxia (IH) in tumors is characterized by fluctuating changes in pO2 

within the disorganized vascular network. A major difference with the chronic 

hypoxia is that the tumor vasculature itself may be directly influenced by 

the hypoxic environment and that the re-oxygenation phases complicate the 

S 163 

usual hypoxia-induced phenotypic pattern. Here, we dissected the IH-driven 

EC pathways leading to radio-resistance. 

Materials: 

Results: We have recently demonstrated that endothelial cell (EC) exposure 

to IH rendered them resistant to radiotherapy and promoted angiogenesis. 

Moreover, an in vivo approach to enforce IH in tumor-bearing mice 

showed that it was associated with less radiation-induced apoptosis within 

both the vascular and the tumor cell compartments. Here, we found that EC 

exposure to cycles of hypoxia-reoxygenation led to the accumulation of the 

hypoxia-inducible factor-1-alpha (HIF-1a during the hypoxic periods while it 

was completely abrogated during the reoxygenation phases. The use of HIF- 

1a-targeting small interfering RNA led us to document that the accumulation 

of HIF-1a during intermittent hypoxia accounted for the higher resistance of 

EC. We also found that the phosphorylation of Akt, ERK and eNOS during the 

reoxygenation phases accounted for cell survival. We identified the stimulation 

of the mitochondrial respiration and the activation of the PI3K/Akt pathway 

during the intermediary reoxygenation periods as the major triggers of 

the stabilization of HIF-1 and cell resistance to radiotherapy. We also found 

that the NOS inhibitor L-NAME further stimulated the IH-driven HIF-1 α accumulation 

and the associated gain in EC survival, thereby mirroring the effects 

of a PI3K/Akt inhibitor. The combination of both drugs however resulted in a 

decrease in EC survival and angiogenesis. 

Conclusions: IH precondition endothelial and tumor cells in such way that 

they are more resistant to apoptosis and more prone to participate in tumor 

progression. Our observations also underscore the potential of drugs targeting 

HIF-1a to re-sensitize the tumor vasculature to anticancer treatments 

as well as the combination of these drugs with anti-angiogenic therapies, in 

particular those targeting NO pathway. 

490 oral 

QUANTITATIVE ASSESSMENT OF THE REPRODUCIBILITY AND 

THE CONSISTENCY OF PROTON BEAM RANGE VERIFICATION 

WITH PET/CT 

A. Knopf 1 , K. Parodi 2 , H. Paganetti 1 , E. Cascio 1 , A. Bonab 3 , T. Bortfeld 

1 

1 MGH, Radiation Oncology, Boston, USA 

2 HEIDELBERG ION THERAPY CENTER, Radiation Oncology, Heidelberg, 

Germany 

3 MGH, Radiology, Boston, USA 

Purpose: A promising method for in vivo and non-invasive monitoring of radiation 

treatments with proton beams is positron emission tomography (PET). 

At Massachusetts General Hospital (MGH) we investigate how accurately 

the proton range can be verified in the patient with offline PET/CT scans. 

In vivo PET measurements are challenged by blood perfusion, variations of 

tissue compositions, patient motion and image co-registration uncertainties. 

Besides these biological and treatment specific factors, the accuracy of the 

method is constrained by the underlying physics processes. This phantom 

study distinguishes physical factors from other factors, assessing the reproducibility 

and consistency of the PET/CT range verification method. 

Materials: A circular SOBP proton field has been delivered to an in house 

designed phantom consisting of poly-methyl methacrylate (PMMA), lung and 

bone equivalent slabs. PET data were acquired in listmode starting within 

15 min after irradiation using a commercial PET/CT scanner. The measured 

PET distributions were compared to simulations of the PET signal based on 

Geant4 and FLUKA Monte Carlo (MC) codes. Besides a range comparison 

at specific positions in the fall-off region of the activity depth profiles, a range 

analysis taking the entire fall-off region into account was performed. The 

range difference between two activity depth profiles was determined by shifting 

their normalized fall-off regions against each other until the minimum of 

the sum of absolute differences in the activity values was found. 

Results: To test the reproducibility of the measured PET signal the irradiation 

and PET scan of the phantom were repeated twice and activation depth 

profiles at identical geometrical positions within the phantom were compared. 

The reproducibility of the measured PET range was found to be in the order 

of 1 mm standard deviation. To test the consistency of the measured PET 

signal activation, depth profiles within identical material arrangements, but at 

different positions within the irradiation field, were compared. The consistency 

of the PET/CT range verification method was found to be in the same 

order as the reproducibility. We found that the shift-method is a more robust 

strategy for range verifications than the comparison of ranges at specific positions 

in the fall-off region, which is sensitive to statistical noise and modeling 

uncertainties. 

Conclusions: This phantom study indicates the physical potential for a millimeter 

accuracy in PET range verification of the dose delivered in proton 

irradiation by commercially available PET/CT scanners despite their coarse 

spatial resolution of about 4-5mm.

S 164 AWARD LECTURE WEDNESDAY, SEPTEMBER 17, 2008 

491 oral 

PRE-TREATMENT VERIFICATION OF THE TARGET POSITION 

IS MOST SIGNIFICANT TO INCREASE OVERALL ACCURACY IN 

PULMONARY HYPO-FRACTIONATED RADIOTHERAPY 

M. Guckenberger 1 , T. Krieger 1 , J. Wilbert 1 , O. Sauer 1 , K. Baier 1 , A. 

Richter 1 , M. Flentje 1 

1 JULIUS-MAXIMILIANS UNIVERSITY, Department of Radiation Oncology, 

Würzburg, Germany 

Purpose: To evaluate the potential of image-guidance, gated beam delivery 

and continuous intra-fractional target monitoring for margin reduction in hypofractionated 

radiotherapy of pulmonary tumors. 

Materials: Margins necessary for compensation of breathing motion of intrapulmonary 

targets were evaluated using 4D dose calculation based on respiratory 

correlated CT and non-rigid image registration (Pinnacle TPS v 8.1t). 

For 16 pulmonary targets, the macroscopic tumor was defined as clinical target 

volume CTV in the CT pulmonary window of the 4D-CT series with the 

target in the time-weighted average position. Multi-field treatment plans were 

generated with a D95 dose of 80% to the CTV and maximum dose of 100%. 

The loss of dose to the CTV due to breathing motion was calculated and 

field-size was stepwise increased until loss of dose was completely compensated. 

Inter-fractional and intra-fractional set-up errors were evaluated 

based on kilo-voltage cone-beam CT (CBCT) studies acquired prior to and 

after stereotactic body-radiotherapy for 50 pulmonary targets (1-8 fractions 

per treatment). Delineation uncertainties of 1mm (1SD) were assumed. Margins 

for compensation of uncertainties were calculated using the van Herk 

recipe. 

Results: The mean motion amplitude of the 16 targets was 12mm±5mm. A 

non-linear function between motion and increase of field size for compensation 

of dose loss to the CTV was observed: increase of field size of 1.3mm 

2.8mm and 6.4mm around the CTV was sufficient for compensation of motion 

amplitudes of 5mm, 10mm and 20mm, respectively. Image-guided protocols 

using the bony anatomy as surrogate (IGRT-bone) and matching the tumor 

itself (IGRT-tumor) were simulated. For no-gated treatment with patients 

breathing freely, IGRT-bone and IGRT-tumor required margins of 11.2mm and 

6.6mm around the CTV in superior-inferior direction for complete compensation 

of residual uncertainties assuming 10mm motion amplitude. Using 

gated beam delivery (assuming no residual motion), margins of 8.4mm and 

3.8mm were calculated for IGRT-bone and IGRT-tumor, respectively. Continuous 

intra-fractional monitoring of the target would additionally allow 1.3mm 

margin reduction for both gated and non-gated treatments. 

Conclusions: Rather small margins were sufficient for compensation of dose 

loss due to breathing induced motion of pulmonary targets. Verification of the 

target position prior to treatment was most significant for increasing overall 

accuracy. 

Van der Schueren Award 

492 speaker 

EMMANUEL VAN DER SCHUEREN AWARD 

A. Begg 1 



THURSDAY, SEPTEMBER 18, 2008 TEACHING LECTURE 

Thursday, September 18, 2008 


Evidence based medicine: anal cancer 

493 speaker 

TREATMENT OF ANAL CANCER 

J. F. Bosset 1 

1 HÔPITAL UNIV. JEAN MINJOZ, Besançon, France 

Ten years ago chemoradiotherapy was established standard treatment in anal 

carcinoma. The treatment scheme being a combination of external beam 

irradiation to a total dose of 50-60 Gy on the gross tumour volume with 5- 

FU Mitomycin C delivered during radiotherapy.Since that time, a number of 

questions emerged, some have been resolved. The main points that will be 

discussed are : 1. Optimisation of the disease stage determinations, (is there 

a place for PET) ? 2. Is CMT standard for all invasive cancer ? 3. Is there an 

agreement on the dose (in Gy) that is needed for elective node radiotherapy, 

and for the gross disease ? 4. When the inguinal region should be irradiated 

? 5. Is a gap acceptable or is it detrimental ? 6. Is there a place for surgery 

? 7. Is standard CMT sufficient for large tumors ? 8. Is there any other 

chemotherapeutic combined treatment acceptable ? 9. Is there a place for 

upfront chemoradiotherapy ? 10. How to assess late toxicities.These main 

topics will be developed. 

Cancer epidemiology 

494 speaker 

THE CHANGING PICTURE OF CANCER IN EUROPE 

H. Storm 1 

1 DANISH CANCER SOCIETY, Cancer prevention Documentation, Køben- 

havn, Denmark 

It was estimated that 3 191 600 new cancer cases (excluding non-melanoma 

skin cancer) and 1 703 000 cancer deaths occurred in 2006 in Europe of 

which 53% and 56% respectively occurred in men. The increase in 2 years 

was estimated to be 300 000 cases. The ageing of the European population 

alone will increase these numbers in the future and cancer will continue 

to be a major public health problem. The most common cancer was breast 

cancer followed by colorectal and lung whereas the mortality was highest for 

lung followed by colorectal, breast and stomach cancer. The cancer picture is 

however changing, both with respect to incidence, mortality and survival and 

the differences between the European countries with the respect to these 

variables are under intense surveillance and study. This has lead to the development 

and interest in national cancer control plans although none so far 

has been developed for EU. The need for better and comparable data is obvious, 

and clearly demonstrated in the collaboration by the Nordic countries 

on incidence, mortality, prevalence, survival, and predictions for the future. 

The presentation will be based on recent European and Nordic publications 

and available databases and software that can demonstrate the changing picture 

of cancer in Europe and point to plausible reasons behind the observed 

changes. Better access to care, early diagnosis and better treatment will 

influence mortality, survival and prevalence whereas prevention like actions 

to curb the tobacco epidemic will reduce the incidence of several cancers 

and other important exposures may led to incidence increase on top of the 

increase caused by ageing 

495 speaker 

MICRORNA AND CANCER 

R. Agami 1 



Impact of new RT technology on margins 

496 speaker 

S 165 

ARE MARGINS STILL REQUIRED IN IMAGE GUIDED RADIOTHER- 

APY? 

M. van Herk 1 

1 THE NETHERLANDS CANCER INSTITUTE, Department of Radiation 

Oncology, Amsterdam, Netherlands 

The advent of image guided radiotherapy (IGRT) has allowed major improvements 

in the accuracy of treatment delivery and is currently causing a shift towards 

hypofractionation. Due to these changes, the necessity and magnitude 

of treatment margins is often discussed. It is the purpose of this presentation 

to discuss treatment margins in the context of these new techniques. Treatment 

margins, from the CTV (Clinical target volume) to PTV (Planning Target 

volume), are used to ’absorb’ geometrical uncertainties that are introduced in 

all steps of the radiotherapy procedure, i.e., such that small errors in positioning 

of the tumor relative to the treatment beam do no lead to unacceptable 

underdosage of the CTV. This concept is equally valid in IGRT and classical 

radiotherapy, although the source and magnitude of the uncertainties are 

partly different. The main uncertainty that is identical independent of the treatment 

technique is the uncertainty related to target volume delineation. It has 

been shown that if the ’average’ observer would be correct, that a margin 

equal to 2.5 the SD of the local shape variations is required to ensure that the 

target volume of one observer is adequately treated when the target volume 

of another observer is used to base the treatment plan on. Image guidance 

will next deal with ’classical’ sources of uncertainty such as setup error and 

organ motion. However, a new source of uncertainty is introduced with image 

guidance: the process of image registration has a finite accuracy, as well as 

the correction method to reposition the patient or the tumor. For some sites, 

like brain, these uncertainties are very small. For other sites, such as the 

prostate, the accuracy is limited due to low contrast and deformations. Even 

if implanted markers are used, the accuracy is limited by deformations, mainly 

for the seminal vesicles relative to the markers, requiring a margin of almost 

1 cm. Finally, there will at least be some motion between the time that the 

image for image guidance is taken and the time of treatment. It is important 

that these uncertainties are recognized, quantified and taken into account. 

For hypofractioned radiotherapy of the lung, these uncertainties range from 

1-2 mm SD. Another aspect that requires attention is the effect of limiting the 

number of fractions on the margin equations. These are generally derived 

assuming that random errors can be modeled as a blurring of the dose distribution. 

With a few fractions this assumption may be invalidated. However, 

because delineation uncertainty dominates systematic errors, and respiration 

induced motion dominates random errors, this effect turns to be negligible in 

many cases.However, density effects and prescription dose levels used do 

affect the margin equations and should be taken into account. In conclusion, 

margins are still highly important in the era of image guidance, and maybe 

even more then before, because a realistic view is required to estimate margins 

that are now determined by other errors sources that did not exist before 

or have a higher impact. 

497 speaker 

EVIDENCE BASED MEDICINE: GYNAECOLOGICAL TUMOURS 

E. Van Limbergen 1 

1 UNIVERSITY HOSPITAL GASTHUISBERG, Department of Radiation 



498 speaker 

QUALITY MANAGEMENT OF ION BEAM THERAPY 

H. Kooy 1 , M. Engelsman 1 

1 MASSACHUSETTS GENERAL HOSPITAL & HARVARD MEDICAL SCHOOL, 

Department of Radiation Oncology, F H Burr Proton Therapy Center, Boston, 

USA 

Quality management in radiotherapy ensures that all the activities necessary 

to design, develop and implement a treatment are effective and efficient with 

respect to the system and its performance # . Quality management can be 

considered to have three main components: quality assurance, quality control, 

and quality improvement. Quality management is focused not only on 

quality, defined in ISO 9000 as "Degree to which a set of inherent characteristics 

fulfills requirements," but also the means to achieve it. Quality management 

therefore uses quality assurance and control of processes to achieve 

more consistent quality. Quality management in radiotherapy has the primary 

purpose to deliver the intended dose, as acurately as possible, to the target 

volume. As such there is a strong, and perhaps biased, emphasis on 

the radiotherapy equipment with a lesser emphasis on the cause-and-effect 

relationship of the other physical processes, such as captured in treatment

S 166 SYMPOSIUM THURSDAY, SEPTEMBER 18, 2008 

planning, or procedural aspects. Radiotherapy has a long history and quality 

management as such has been very much experience-based and has had 

the opportunity to incrementally incorporate new technologies. Finally, quality 

management continuous to evolve, based on accumulated experience within 

the field and new methodologies in general. Ion therapy, while sharing the 

basic functional processes of conventional radiotherapy, introduces significantly 

new concepts and deployment features. The radiation equipment has 

no commonality with conventional equipment, is considerably more complex, 

and often has no track record of operation or a foundation of experience by 

its users. Furthermore, the modality, ions, introduces new physics whose primary 

feature, with respect to the patient, is the high demand of spatial and 

dosimetric precision. While, again, the quality management procedures from 

conventional radiotherapy apply, these must be considered anew in light of 

the cause-and-effect relations introduced as a consequence of ion physical 

processes and controls.The radiotherapy patient experiences a sequence of 

fundamental processes: imaging, treatment planning, and treatment delivery. 

Ion therapy has consequences for each of them. One physical property, 

the one of primary clinical relevance, is the ion Bragg peak. The determination 

and control of its position within the patient is the primary new element 

for quality management. Its position is highly dependent on accurate tissue 

stopping power determination and accurate representation, much more so 

compared to photon radiation, of the time-dependent representation of the 

patient. This impacts imaging, especially 4D imaging, subsequent treatment 

planning, and treatment delivery. For each process, we need to ensure that 

the patient remains within the envelop of uncertainties as characterized by 

the overal process. Finally, the quality management process of the equipment 

needs to be evaluated in terms of the fundamental physical processes.In this 

lecture, we will introduce the basics of ion therapy physics and illustrate the 

quality management program in terms of the individual processes and causeand-effect 

relationships. # Adapted from the wikipedia.org entry. 

499 speaker 

EVIDENCE BASED MEDICINE: PROPHYLACTIC CRANIAL IRRADI- 

ATION 

M. Stuschke 1 , C. Poettgen 1 

1 UNIVERSITÄTSKLINIKUM ESSEN, Department of Radiation Oncology, 

Essen, Germany 

Efficacy and potential risks of prophylactic cranial irradiation (PCI) in small 

cell lung cancer patients will be discussed as well as salvage options for brain 

metastases. The risk of brain metastases in limited disease small cell lung 

cancer (SCLC) and in complete response after induction chemotherapy is 

about 60% at 3 years. PCI can reduce this risk by more then 50% (relative 

risk 0.46) and improve survival. PCI is a standard treatment option for SCLC 

in complete remission for patients with limited and nowadays also for extensive 

disease and should be considered for patients with partial response. The 

supporting level 1 data form randomized controlled trials will be presented. 

The dose response relation of tumour control in the brain as well as the timing 

of PCI and observed long term side effects from prospective as well as 

retrospective studies will be discussed. In NSCLC, a similar underlying risk 

of brain metastases exists and the brain is the predominant site of failure in 

Stage III NSCLC after multimodal therapy. Chemotherapy does not prevent 

brain metastases in NSCLC and PCI is effective with a similar dose response 

as in SCLC. However, the data base for the use of PCI is NSCLC is much 

smaller than in SCLC and PCI should be used here within clinical trials. Further 

developments in radiotherapy as avoidance of sensitive structures in the 

brain are discussed. 

Symposium 

New trends in the treatment of gastric cancer 

500 speaker 

TARGET VOLUMES FOR RADIOTHERAPY IN GASTRIC CARCI- 

NOMA 

V. Valentini 1 

1 POLICL. UNIV. "A. GEMELLI", Department of Radiation Oncology, Roma, 

Italy 

Gastric cancer is still a major problem for the oncologists. Surgery is the 

main therapeutic approach; usually, a complete surgical resection is necessary 

to offer potentially curative therapy to patients with adenocarcinoma of 

the stomach. However, many patients with more locally advanced tumours 

will experience local and distal recurrences. Radiotherapy + chemotherapy 

seems to improve local control and survival, as rencent meta-analyses have 

shown. The toxicity was always reported as major problem limiting the prescription 

of radiotherapy until some years ago, and it was related mainly to 

the large treatment volumes and to the not optimal technology available to 

shield the surrounding structures at risk. During the last ten years the radiation 

therapy technique dramatically improved its potential, but, in spite of 

the standardization of the surgical approach to the locoregional nodes, the 

clinical target definition of the nodal area for radiotherapy is still missing. The 

aim of this presentation is to review the incidence of nodal area involvement 

according to the tumour location and stage, the definition of firm anatomical 

references to identify in planning CT these nodal areas, and to propose how 

to tailor the CTV prescription accordingly. 

501 speaker 

WHY NOT A SURGICAL TREATMENT? 

C. van de Velde 1 

1 LEIDEN UNIVERSITY MEDICAL CENTER, Surgery, Leiden, Netherlands 

Since the first successful gastric resection by Billroth in 1881, substantial 

research has been performed to evaluate results and improve outcomes of 

gastrectomy. Fortunately, results have indeed improved. Still, the risk-benefit 

ratio should be calculated for each patient so the procedure is known to represent 

optimal treatment. The extent of disease, the operative procedure, and 

the selection of the patient all play a crucial role in optimizing outcome. 

The JRSGC has provided guidelines for the standardization of surgical treatment 

and pathological evaluation (1). As a result of these guidelines, physicians 

now speak the same language concerning gastric cancer, and the possibility 

has been created to compare different studies on this subject. Nevertheless, 

considerable variation is still seen in results of gastric cancer treatment. 

Several surgical-, patient-, tumor-, and treatment-related factors may 

play a role in this variation. 

Resectability of gastric cancer has increased in the past decades, not only 

because of earlier detection but also due to the technical ability to perform 

extended operations. Pessimism about outcomes may prevail, however, and 

lead to negative attitudes that may become self-fulfilling. If the surgeon performs 

palliative procedures because of a belief that gastric cancer is nearly 

always incurable at presentation, this low expectation will be fulfilled (2). Conversely, 

inappropriately aggressive surgery in unfit patients may lead to increased 

postoperative morbidity and postoperative mortality without improving 

long-term outcome (3). 

Tumor stage is an important prognostic factor in gastric cancer. A strong relationship 

is found between depth of invasion and the occurrence of lymph node 

metastasis. The occurrence of lymph node metastasis is in itself strongly related 

to 5-year survival. Because the incidence of lymph node metastasis is 

known to be greater in the node stations near the tumor than in more distant 

ones (4), and the distance between tumor and lymph node shows a direct 

relationship with survival (5), the question remains as to which patients can 

benefit from an extended lymph node dissection. 

In Japan, where extended (D2) dissections are standardized, results from 

gastric cancer treatment are encouraging. In Western countries, nonrandomized 

trials seemed to indicate that survival may be better for patients undergoing 

a D2 dissection, although the Japanese results could not be matched. As 

noted previously, two large randomized Western studies, the DGCT and the 

MRC, have compared D1 and D2 dissections (6,7), and final results are now 

available (8,9). These studies show that the group undergoing D2 dissection 

experienced higher morbidity and hospital mortality without showing a significantly 

longer survival. The conclusion is that these studies do not generally 

support the standard use of extended (D2) lymph node dissection in Western 

patients with gastric cancer. 

With a mean survival of 45% at 5 years, the results of the Dutch D1 and D2 

trials for both treatment arms are far better than the previous experience in 

Western countries. This indicates the benefit of trial participation with optimal 

selection, use of surgical techniques, compliance in dissecting the appropriate 

lymph nodes, and postoperative care throughout the study. 

The use of subtotal versus total gastrectomy for tumors in the distal part of the 

stomach has often been a point of discussion. From previous studies, subto-

THURSDAY, SEPTEMBER 18, 2008 SYMPOSIUM 

tal gastrectomy appears to carry less morbidity and achieve the same survival 

rates, provided that an adequate tumor free margin can be obtained. Resection 

line involvement should be evaluated perioperatively by frozen-section 

examination. In all studies, resection of spleen and pancreas led to increased 

hospital mortality and increased morbidity, which eventually resulted in a decreased 

survival. Therefore, in Western countries, resection the pancreas 

and spleen are recommended only if tumor ingrowth prohibits a possible curative 

resection. 

Age is found to be an important prognostic factor among Western patients. 

Although the resectability and curability rates do not differ across age groups, 

both a significant increase in morbidity and mortality and a markedly worse 

survival rate are seen with increasing age. 

The presence of disease in lymph node station 16 (N4) or a positive result on 

cytologic examination of abdominal fluid is associated with poor prognosis. 

Consequently, extended resections should be avoided in these situations. 

The technical skills of the surgeon may also influence outcomes in gastric 

surgery. Only in the German Gastric Cancer Study was a significant difference 

in outcomes found between surgeons with more or less experience, 

especially with regard to the occurrence of anastomotic leakage. Other trials 

failed to show a significant difference. Although morbidity in Western countries 

exceeds that in Japan, no significant difference in morbidity and hospital 

mortality is found for Japanese surgeons operating on Western patients and 

for Western surgeons (10). Thus, the difference in results between Japanese 

and Western studies does not seem to be caused by the skills of the surgeons. 

Nevertheless, a learning curve for performance of extended resections 

has been shown by McCulloch (2,11). This may be one of the reasons 

that more experienced hospitals show a lower morbidity and hospital mortality 

(12). Other reasons for better results may be better patient selection, a 

better pathological analysis (stage migration phenomenon), better preoperative 

staging, and the possibility of (neo)adjuvant chemotherapy. In view of the 

much lower postoperative mortality rates reported by specialized centers, the 

treatment of gastric cancer should be the territory of a multidisciplinary team 

of committed specialists in all areas to achieve optimal results. Preoperative 

assessment of the lesion and the patient, as well as perioperative management, 

are as important as the operation itself (13). Promising results from 

genomic profiling and from nomograms that predict disease-specific survival 

may, in the near future, help discriminate between patients with a high risk 

of relapse and select those patients who will most likely benefit from tailored 

multimodality treatment. 

References 

1. Kajitani T. The general rules for the gastric cancer study in surgery and 

pathology. Part I. Clinical classification. Jap J Surg 1981;11(2):127-139. 

2. McCulloch P, Niita ME, Kazi H, Gama-Rodrigues JJ. Gastrectomy with extended 

lymphadenectomy for primary treatment of gastric cancer. Br J Surg 

2005;92(1):5-13. 

3. Gilbertsen VA. Results of treatment of stomach cancer. An appraisal 

of efforts for more extensive surgery and a report of 1,983 cases. Cancer 

1969;23(6):1305-1308. 

4. Maruyama K, Gunven P, Okabayashi K, Sasako M, Kinoshita T. Lymph 

node metastases of gastric cancer. General pattern in 1931 patients. Ann 

Surg 1989;210:596-602. 

5. Sasako M, McCulloch P, Kinoshita T, Maruyama K. New method to evaluate 

the therapeutic value of lymph node dissection for gastric cancer. Br J 

Surg 1995;82(3):346-351. 

6. Hartgrink HH, van de Velde CJ, Putter H, et al. Extended lymph node dissection 

for gastric cancer: who may benefit? Final results of the randomized 

Dutch gastric cancer group trial. J Clin Oncol 2004:22(11):2069-2077. 

7. Cuschieri A, Fayers P, Fielding J, et al. Postoperative morbidity and mortality 

after D1 and D2 resection for gastric cancer: preliminary results of the 

MRC randomized controlled surgical trial. Lancer 1996;347:995-999. 

8. Bonenkamp JJ, Hermans J, Sasako M, van de Velde CJ. Extended lymphnode 

dissection for gastric cancer. Dutch Gastric Cancer Group. N Engl J 

Med 1999;340(12):908-914. 

9. Cuschieri A, Weeden S, Fielding J, et al. Patient survival after D1 and D2 

resections for gastric cancer: long-term results of the MRC randomized surgical 

trial. Surgical Cooperative Group. Br J Cancer 1999;79(9-10):1522-1530. 

10. Bonenkamp JJ, for the Dutch Gastric Cancer Group. D1 versus D2 dissection 

for gastric cancer (comment on letters). Lancet 1995;345:1517-1518. 

11. Parikh D, Johnson M, Chagla L, Lowe D, McCulloch P. D2 gastrectomy: 

lessons from a prospective audit of the learning curve. Br J Surg 

1996;83(11):1595-1539. 

12. Meyer HJ. The influence of case load and the extent of resection 

on the quality of treatment outcome in gastric cancer. Eur J Surg Oncol 

2005;31(6):595-604. 

13. Sasako M. Risk factors for surgical treatment in the Dutch Gastric Cancer 

Trial. Br J Surg 1997;84(11):1567-1571. 

502 speaker 

WHY NOT PREOPERATIVE CHEMORADIATION? 

E. Van Cutsem 1 

1 UNIVERSITY HOSPITAL GASTHUISBERG, Department of Digestive Oncol- 

ogy , Leuven, Belgium 

Surgery remains the cornerstone of the management of patients with re- 

S 167 

sectable gastric cancer. Many patients will develop however a recurrence 

after surgical resection. It has been shown that the outcome of patients 

with resectable gastric cancer can be improved by a strategy of perioperative 

(pre- en postoperative) chemotherapy (European studies), by postoperative 

chemoradiotherapy (US study) and by an adjuvant chemotherapy with 

S1 (Japanese study). Based on these randomized studies showing an improved 

survival of patients with resectable gastric cancer with a multimodality 

approach, an (neo-)adjuvant therapy is actually recommended. In an effort 

to improve downsizing of large tumors and to increase the R0 resection, a 

preoperative chemoradiotherapy has been explored in non-metastatic gastric 

cancer. Although preoperative chemoradiotherapy in gastric cancer is 

still investigational, recent single- and multi-institutional studies have shown 

a high R0 resection rate even in large tumors and a complete response rate 

of ± 20 % in careful selected patients. These studies also reported a better 

tolerance of preoperative chemoradiotherapy compared to postoperative 

chemoradiotherapy and an acceptable postoperative complication rate. The 

studies demonstrate also a favourable disease free survival and a long survival 

in patients who can undergo an R0 resection and in the patients who 

have a pCR after preoperative chemoradiotherapy. However; a significant 

number of potentially resectable patients have interval progression on or after 

the preoperative chemoradiotherapy. Although preoperative chemoradiotherapy 

is a promising treatment strategy in resectable gastric cancer, its actual 

role is not yet clear and has to be validated in larger clinical trials. Amongst 

the open questions that have to be answered, are questions on patient selection: 

stage (locally advanced or also smaller tumors only), type (localized 

or diffuse type) and localisation (gastroesophageal junction adenocarcinoma 

versus other localisations) Since it is unlikely that all patient with gastric cancer 

benefit from a neoadjuvant chemotherapy or chemoradiotherapy, optimal 

selection strategies for patients exposed to multimodality treatments, will have 

to be done. Here also the search for predictive and prognostic molecular 

markers and for ways of predicting early in the treatment the response and 

benefit of the treatment via FDG-PET scan may be important tools for optimizing 

the treatment strategy. 

503 speaker 

WHY NOT POSTOPERATIVE CHEMO-RADIATION? 

W. Budach 1 

1 UNIVERSITY CLINIC HEINRICH-HEINE UNIVERS. DUSSELDO, Düsseldorf, 

Germany 


Waiting time in radiotherapy - Does it matter? 

504 speaker 

INTRODUCTION AND OUTLINE OF THE PROBLEM 

J. Overgaard 1 



505 speaker 

DO TUMORS PROLIFERATE DURING WAITING TIME? EXAMPLE 

FROM SQUAMOUS CELL CARCINOMA OF HEAD AND NECK 

A. R. Jensen 1 



506 speaker 

THE RELATIONSHIP BETWEEN WAITING TIME FOR RADIOTHER- 

APY AND CLINICAL OUTCOMES 

W. MacKillop 1 

1 QUEEN’S UNIVERSITY CANCER RESEARCH INSTITUTE, Kingston, Ontario, 

Canada 



507 speaker 

MODELING AND PREDICTING THE IMPACT OF DELAY ON THE 

OUTCOMES OF RADIOTHERAPY 

J. P. Voroney 1 

1 QUEEN’S UNIVERSITY CANCER RESEARCH INSTITUTE, Department of 

Radiation Oncology, Kingston, Ontario, Canada 

Purpose: To outline the evidence that delay affects radiotherapy outcomes, 

emphasizing clinical studies (randomized trials of cancer prevention, randomized 

trials of upfront versus expectant radiotherapy, retrospective cohort studies 

of patients subjected to varying wait time). To review radiobiologic tumour 

control probability (TCP) models based and cell and animal studies and generalized 

to humans. To review single institution studies of (1) a commonly 

measured prognostic factor, tumour volume, that can increase during delay, 

and (2) how this prognostic factor changes with delay i.e. tumour volume doubling 

time. To perform meta-analysis and sensitivity analysis to determine the 

robustness of predictions based on tumour volume and median tumour volume 

doubling times, for head and neck cancer.Methods: Meta-analysis of the 

exponential relationship between tumour volume and local control/survival, 

and meta-analysis of tumour volume doubling times based on systematic review 

of clinical studies.Results: Within head and neck, the relative risk per cc 

increase in tumour volume varies by a factor of 20 between glottic cancers 

and nasopharyngeal cancers. Doubling times by subsite are unavailable in 

head and neck, but vary considerably in primary disease (median 12 weeks 

for head and neck, to 7 years for low risk prostate cancer) and metastic or 

recurrent disease doubles faster (1 week for recurrent head and neck, to 16 

weeks for metastastic prostate cancer). Histology influences doubling time; 

interquartile ranges in doubling time are large, and distributions are lognormal.Conclusions: 

There is strong clinical evidence that delay affects local 

control and survival in patients with head and neck cancer. Simple radiobiologic 

models with only two parameters, that can be estimated directly from 

clinical studies, predict results of delay seen in head and neck studies. The 

relevant predictors are the ratio of the delay time to the tumour volume doubling 

time, and the product of the tumour volume and the rate at which prognosis 

changes with volume. Parameter values, however, vary considerably 

within and among sites, and for less common diseases, in some cases no 

studies have been done from which appropriate parameters could be estimated. 

508 speaker 

CONCLUSION: HOW TO TRANSLATE THE EVIDENCE INTO PRAC- 

TICAL CLINICAL GUIDELINES 

W. MacKillop 1 

1 QUEEN’S UNIVERSITY CANCER RESEARCH INSTITUTE, Kingston, Ontario, 

Canada 


Combining radiotherapy and immunotherapy: 

new concepts 

509 speaker 

RADIATION MODULATES THE PEPTIDE REPERTOIRE, ENHANC- 

ING MHC CLASS I EXPRESSION AND IMPROVING ANTI-TUMOR 

IMMUNO-THERAPY 

J. Neefjes 1 , X. Qiao 1 , B. Pang 1 

1 NKI-AVL, Tumor Biology, Amsterdam, Netherlands 

MHC class I molecules present peptides, derived from proteins degraded by 

proteasomes, to the immune system. Killer cells (CTL) may recognize these 

MHC class I-peptide combinations and respond by killing cells expressing 

such combinations. Hence viral-infected cells, transplanted organs and other 

cells expressing non-self antigens are cleared. In principle tumors may be 

cleared as well which is the rationale behind tumor-immunology. Here patients 

are vaccinated in various ways to boost the immune system against 

tumors. The results on tumor control are however relatively minor and major 

advances have to be developed before this can be successfully applied. 

We have observed that ionizing radiation increases the intracellular peptide 

pool for various reasons. As a result, MHC class I expression is increased in a 

dose-dependent manner and so is the immune response to radiation-exposed 

cells. We subsequently tested whether the combination of radiation and immunotherapy 

had additive effects on tumor clearance. Mouse tumors were locally 

exposed to radiation before adoptive transfer of tumor-specific CTL. Tumors 

were only cleared by combining radiotherapy with immunotherapy. This 

approach combines the target-selectivity of immunotherapy with the spatialselectivity 

of radiotherapy and may be an essential boosting mechanism for 

successful immunotherapy against human tumors. Are other combinations 

also improving tumor therapy? We have noted major effects of the topoIIinhibitor 

doxorubicin on the chromatin structure of exposed cells in a timedependent 

manner. We will present data where chemotherapy is combined 

with radiotherapy under different cellular states following doxo-treatment with 

different results on cell toxicity. These results show that doxorubicin-resistant 

cells can be eliminated when low dose-radiation is applied at a defined time 

and explains the molecular basis for this effect. 

510 speaker 

COMBINING RADIOTHERAPY AND IMMUNOTHERAPY: CLINICAL 

TRANSLATION 

S. Formenti 1 , K. Freedman 1 , S. Adams 1 , M. Fenton-Kerimian 1 , M. 

Donach 1 , S. Demaria 1 

1 NYU SCHOOL OF MEDICINE, Radiation Oncology, New York, USA 

Standard cancer treatment aims at achieving cancer cell death. The process 

also results in releasing antigens to dendritic cells for cross-presentation to 

T-cells, a potential opportunity for induction of an immune response to the 

tumor. Many barriers exist to inhibit this course, however. Over the past 

several years, we have explored preclinically strategies to overcome these 

barriers, with promising results. For instance, we in a pre-clinical model of 

syngeneic mammary carcinoma in immunocompetent mice radiation treatment 

to an established tumor nodule when combined a DC growth factor was 

able to induce a T cell-mediated anti-tumor immune response inhibiting tumor 

growth outside of the field of radiation (Int. J. Radiat. Oncol. Biol. Phys. 

58:862-70, 2004). A "proof-of principle" clinical trial was derived, aiming at 

detecting a response outside the radiation field after GM-CSF administration 

(as DC growth factor) in metastatic cancer patients. This type of effect of radiotherapy 

was originally described as "abscopal", from the latin "ab scopus", 

away from the target. Eligible were patients with metastatic cancer with at 

least 3 measurable lesions, who had no change or progression during systemic 

chemotherapy. The protocol required that the same systemic therapy 

be maintained but radiation therapy to be added to one lesion, 3.5 Gy X 10, 

over 2 weeks. Day seven (after one week of radiation) GM-CSF, 125 micrograms/kg, 

was given s.c., daily for 14 days. Abscopal response was defined 

as a measurable (RECIST) response in any of the lesions outside the radiation 

field, assessed by PET-CT. A total of 14 patients accrued to this trial. 

Tumor histology was: lung cancer (8), breast cancer (4), bladder (1), eccrine 

(1). Median age was 62 (range 41-89). A total of 26 cycles of therapy were 

administered (10 patients received 2 cycles) during chemotherapy. Grade 

3 toxicity were: 2 lymphopenia, 1 thrombocytopenia, 1 anemia and 1 nausea/vomiting. 

Most common toxicity consisted of fatigue: grade 3 in 1 case 

and grade 1-2 in ten. Two patients suffered syncopal episodes, likely related 

to EDTA in the formulation of GM-CSF used.Twelve patients can be evaluated 

for response (i.e. have complete treatment and have had PET/CT before and 

following therapy): four have achieved an abscopal response (30%) classified 

as a partial response of at least one lesion outside the treatment field. In five 

patients a decrease in SUV of non-irradiated lesions was observed on PET 

scan, preceded by a "flare" effect at PET in three cases. The combination of 

radiation therapy and GM-CSF resulted in a systemic effect outside the radiation 

field, in 30% of patients who either did not to respond or progress during 

chemotherapy. This trial confirms in the clinic the preclinical feasibility and efficacy 

of harnessing the local radiotherapy effects to synergize with immune 

therapy. A novel application of radiotherapy as an adjuvant strategy to cancer 

immunotherapy is introduced. 

511 speaker 

NOVEL APPROACHES TO THE DEVELOPMENT OF RADIO- 

IMMUNOTHERAPY COMBINATIONS IN CANCER 

T. Illidge 1 

1 UNIVERSITY OF MANCHESTER, School of Cancer and Imaging Sciences, 

Paterson Institute for Cancer Research, Manchester, United Kingdom 

Recent advances have begun to underline the importance of enhancing 

our understanding of the interactions between radiotherapy (RT) and immunotherapy 

in the treatment of cancer. These interactions can be with vector 

such antibody (mAb) targeted radiation as used with radioimmunotherapy 

(RIT) or with external beam radiation therapy (EBRT) in combination with immunotherapy. 

Using preclinical models of RIT our group has been able to 

provide new insights out the mechanisms of action of RIT and to investigate 

the relative contributions of targeted radiation and monoclonal antibody (mAb) 

effector mechanisms to the induction of tumour cell death and long-term successful 

clearance of tumour. Recent work has focused on how anti-CD20 

mAb and RT interact to induce tumour cell death secondary to a form of "cytoplasmic" 

cell death that appears to bypass the apoptotic machinery. Our 

current research focuses on further defining this pro-death signalling pathway 

in this novel type of antibody induced cell death. In addition to investigating 

the mode and mechanisms of RT induced tumour cell death, we are 

interested in understanding the effects that RT has on the host immune response. 

In this work we examine how local RT and systemically delivered 

targeted radiation damage to tumour cells can alert the immune system


and how anti-tumour activity can be promoted using immunoregulatory 

mAb such anti-CD40. We are interested in further understanding how 

RT increases immunogenicity of tumour cells and how the tumour microenvironment 

interacts with dying tumour. This research involves investigating 

the roles played by the key host immune effector cells involved in the 

response to and clearance of dying tumour, including macrophages, dendritic 

cells and NK-cells. Novel immunostimulatory mAb and immunoligands are 

used to augment immune effector responses to tumour by blocking or stimulating 

co-receptors in the immune system. Current targets and some of the 

factors which have been found to be of potential significance in combining RT 

with immunotherapy will be discussed. 

Revisiting the concept of margins in treatment 

planning 

512 speaker 

IMPROVING TARGET DEFINITION BY CORRELATING PATHOLOGY 

WITH PRETREATMENT IMAGING 

K. Gilhuijs 1 

1 THE NETHERLANDS CANCER INSITUTE - ANTONI VAN LEEUWENHOEK 

HOSPITAL, Diagnostic Oncology, Amsterdam, Netherlands 

Purpose/objective: Advances in treatment planning, IMRT and IGRT allow 

dose escalations to optimize local control without increasing normal-tissue 

complications. Now, uncertainty in the extent of disease becomes the major 

limiting factor. CT, MRI and PET provide anatomical and functional information, 

but large variations in target delineation occur while the true disease extent 

remains unknown. The aim of this pathology-validated imaging research 

is to incorporate correlations of histopathology and pretreatment imaging in 

the selection of GTV and CTV in individual patients and subgroups of patients. 

Methods/materials: We focus on lung and breast as these sites illustrate 

complementary interests in radiotherapy: reduction of high local recurrence 

rates (lung) and reduction of treated normal tissue (breast). Pathology protocols 

based on complete embedding, serial sectioning and reconstruction 

have been implemented to allow registration of histopathology with pretreatment 

imaging. The GTV at imaging was correlated with histopathology, and 

the incidence of microscopic disease at various distances from the GTV quantified. 

Deformable registration was used to assess deformations between invivo 

imaging and ex-vivo pathology. 

Results: Lung: The GTV at CT and the GTV at PET overestimated the GTV 

at pathology by 4 mm and 3 mm, respectively (n=16). Surrounding islets of 

microscopic disease were found in 50% of the patients. The mean of the 

maximum extension per patient was 5 mm (range 0-9 mm). Due to deformation 

of the excised tissue, the true in-vivo extension may be up to two 

times larger. Breast: Contrast-enhanced MRI depicted unexpected multifocal 

disease in 22% (n=324) of patients scheduled for breast-conserving therapy 

(BCT). MRI accurately depicted the GTV at pathology (0.8 mm mean difference), 

while conventional mammography underestimated it (7.3 mm mean 

difference). Microscopic disease >1 cm from the edge of the GTV was found 

in 53% of patients. Taking microscopic extension and relative position of the 

tumor in the excision specimen into account, the radiation boost CTV could 

potentially be reduced by 26% without loss of tumor coverage. 

Conclusion: Incorporating pathology information through correlation with 

pretreatment imaging provides new information and insights that may optimize 

target volumes, thus increasing local control and reducing involved 

healthy tissue. 

513 speaker 

PLANNING ORGAN AT RISK VOLUME MARGINS IN PRACTICE 

L. P. Muren 1 , U. V. Elstrøm 1 , L. Hysing 2 , T. Wentzel-Larsen 3 , J. Petersen 

4 , Karlsdottir 2 

1 

AARHUS UNIVERSITY HOSPITAL, Depts of Medical Physics and Oncology, 

Aarhus C, Denmark 

2 

HAUKELAND UNIVERSITY HOSPITAL, Dept of oncology and medical 

physics, Bergen, Norway 

3 

HAUKELAND UNIVERSITY HOSPTIAL, Center for Clinical Research, Bergen, 

Norway 

4 

AARHUS UNIVERSITY HOSPITAL, Medical Physics, Aarhus C, Denmark 

The Planning organ at Risk Volume (PRV) was proposed as a simple method 

to account for geometrical uncertainties of organs at risk (ORs) in RT planning 

and evaluation. Both the introduction of IMRT and our increasing knowledge 

about geometrical uncertainties has increased the need for such methods. 

This presentation will initially address issues related to calculation of 

PRV margins. The PRV margin formalism follows in the trail of margin calculations 

for targets, however with additional levels of complexity originating 

in the need to account for the dose/volume response of the OR. A margin 

recipe applicable for rigid ORs has been presented whereas for deformable 

S 169 

ORs, a more direct empirical method has been shown to be useful. Examples 

of the two major potential areas of application of PRVs will be given, 

covering use in IMRT optimisation and in late effect prediction. The IMRT optimisation 

application will be for sino-nasal cancer within the DAHANCA IMRT 

protocol where use of PRVs is advised for all ORs assumed to have a serial 

arrangement. It will be shown that plans optimised with PRVs lead to a reduced 

maximum dose for the relevant ORs compared to plans without PRVs, 

however, at the cost of loss of target dose homogeneity. In on-going work, frequent 

online volumetric imaging data will be used to compare the sensitivity 

of plans optimised with and without PRVs with respect to both set-up errors 

and anatomical changes. Regarding use of PRVs in late effect prediction, 

we have compared the correlation between GI adverse effects (after prostate 

RT) and rectum DVH parameters for both the OR and a set of rectum PRVs 

(with previously derived margin combinations). The initial analysis based on 

acute GI effects data showed that the DVHs of the PRVs had 2-3 times as 

many dose levels correlating significantly to the GI effects compared to the 

DVH for the OR. Currently we are repeating this analysis using DVH and late 

effect data for an extended prostate RT material. For the bowel, we have 

quantified the size of PRVs required to include various levels of the considerable 

internal motion of this organ. The resulting PRVs were large and hence 

also rather unspecific, calling for a more sophisticated solution to account for 

bowel motion. Although PRVs are shown to be useful in IMRT optimisation 

and have potential for improving the correlation with adverse effects, use of 

PRVs is not the final answer. In the same way as passive use of margins 

to account for geometrical uncertainties of the target is not the ultimate solution, 

the role of PRVs in IMRT optimisation will be replaced by patient-specific 

adaptive geometry models, probably combining population-based data with 

individual data acquired before or early in the treatment course. Its potential 

role in improving correlation with adverse effects will be replaced by accurate 

accumulation of 3D OR dose distributions, obtained through daily volumetric 

imaging and deformable registration. 

514 speaker 

MARGINS IN MOTION 

C. Rasch 1 , S. R. van Kranen 1 , E. Lamers 1 , M. van Herk 1 , J. J. Sonke 1 

1 THE NETHERLANDS CANCER INSTITUTE ANTONI VAN LEEUWENHOEKHUIS, 

Radiotherapy, Amsterdam, Netherlands 

Background: Applied margins from CTV to PTV in head and neck cancer 

irradiation are small; in the order of 3-5 mm. Partly this is based on reports 

describing these setup errors in terms of rigid body translations in the order 

of 1.5 mm (1SD). The rigid body approach can only describe an average of 

the local setup variability. Shape changes during radiation treatment might 

play a role on a local level. The impact of CTV to PTV margins on dose to the 

organs at risk depends on the proximity of the OAR’s to the target. By focusing 

the setup correction to areas close to the OAR’s margins can locally be 

reduced, probably decreasing side effects. Local setup corrections however 

will require larger margins at remote area’s, where dosimetric impact is less 

important. 

Materials and Methods: For 38 head and neck cancers patients multiple 

cone beam images were acquired during the course of radiation. Local setup 

errors were determined for multiple anatomical defined regions and compared 

with the setup error for an extensive single region encompassing the vertebrae, 

neck, jaw, clavicle and base of skull. The dose to organs at risk was 

calculated for four patients simulating different setup correction strategies and 

margins based on local setup accuracy. First a conventional rigid body approach 

was simulated with 5 mm CTV-PTV margin in an offline setup correction 

strategy. Second, dosimetric impact was determined for an online setup 

correction strategy focusing on the organs at risk and tumor with differentiated 

margins ranging from 2-7 mm, thus taking patient deformation into account. 

Results: Systematic and random errors for the rigid body approach were 1.2- 

1.5 mm (1SD). Local misalignment was in general larger, systematic errors 

ranged from 1.1-3.4 mm and random from 1.3-2.5 mm. For the four patients 

planned with differentiated margins the dose to the parotid glands and oral 

cavity was reduced from 27-24 Gy and 17-15 Gy respectively. The dose to 

the brainstem remained unchanged. 

Conclusion: Changes in shape give rise to substantial local setup errors. 

By applying differentiated margins and focusing setup corrections to regions 

critical to the outcome of the treatment plan, dose to the OAR’s was reduced 

whilst maintaining target coverage. 

Management of CNS tumours 

515 speaker 

RADIOTHERAPY IN THE MANAGEMENT OF INTRACRANIAL 

MENINGIOMA 

S. Milker-Zabel 1 

1 GERMAN CANCER RESEARCH CENTER (DKFZ), RadiationOncology and 

Radiotherapy, Heidelberg, Germany


Meningiomas are one of the most common primary brain tumours in adults 

accounting from 14-20%. The lesions are usually benign and slowly growing. 

The most common localization is parasagital with 25%, and at the sphenoidal 

wings with 20%. Rare subtypes concerning the localization are cavernous 

sinus meningioma with 6%, optic nerve sheath meningioma with 2% and 

meningiomas located at the clivus. Total resection is the standard treatment 

if the tumor is resectable and if there are no contraindications for surgery. As 

an alternative we have the possibility for radiotherapy, like fractionated stereotactic 

radiotherapy (FSRT), intensity-modulated radiotherapy (IMRT), proton 

beam radiotherapy and stereotactic radiosurgery (SRS). Regarding the literature 

the potential of these radiotherapeutic techniques will be discussed. 

In case of inoperability due to the localization of the meningioma or due to 

co-morbid conditions of the patients, and after subtotal resection stereotactic 

radiotherapy can provide durable local control rates up to 95-100% in benign 

meningiomas. The increased incidence of local recurrence in patients with 

WHO grade II and III meningiomas had led to the policy of offering routine radiation 

therapy even following complete resection. Fractionated stereotactic 

radiotherapy and well as intensity modulated radiotherapy is useful for larger 

complex shaped tumors closely approximating critical structures, like the optic 

system (chiasm, optic nerves) and the brainstem. As reported in the literature 

excellent local control rates ranging from 80% to 100% can be achieved with 

FSRT with a low risk of side effects ranging between 0% and 9.7%. Only a 

few data exist about proton beam radiotherapy in meningioma. The results 

are comparable to those of SRS and FSRT/ IMRT. SRS is useful in smallto 

moderate-sized lesions with a maximal diameter < 3 cm and a distance 

to the optic system/ chiasm / optic nerves > 5 mm. The risk for treatment 

related side effects for SRS is also relatively low ranging between 2% and 

27%. Stereotactic radiosurgery and fractionated stereotactic radiotherapy as 

well as IMRT and proton beam radiotherapy are complementary techniques 

appropriate for different clinical scenarios. Compared to radiosurgery, fractionated 

techniques have the additional radiobiological advantage of fractionation 

to allow normal tissue sparing. In patients with an atypical or malignant 

meningiomas proton beam radiation therapy or a combination of photon irradiation 

and proton boost may be advantageous concerning local control and 

disease-free survival. 

516 speaker 

CRANIO-SPINAL AXIS (CSA) RADIOTHERAPY: IMPROVEMENTS 

IN TECHNIQUE - FROM CONVENTIONAL TO CT PLANNED AND 

PRONE TO SUPINE. 

H. Taylor 1 , F. Saran 1 , A. Mosleh-Shirazi 2 , A. Warrington 3 , V. N. Hansen 

3 , S. Eagle 1 , T. Greene 1 

1 

ROYAL MARSDEN NHS FOUNDATION TRUST, Radiotherapy Department, 

Sutton, United Kingdom 

2 

NAMAZI HOSPITAL, SHIRAZ UNIVERSITY OF MEDICAL SCIENCES, 

Radiotherapy Department, Shiraz, Iran Islamic Republic of 

3 

INSTITUTE OF CANCER RESEARCH AND ROYAL MARSDEN NHS TRUST, 

Joint Department of Physics, Sutton, United Kingdom 

Radiotherapy of the CSA is indicated in primary tumours with a high propensity 

to spread through the CSF (e.g. PNETs). It necessitates multiple abutting 

beams to ensure homogenous cover of the target volume. Traditionally this 

technique has been delivered prone due to technical and mechanical limitations 

of planning equipment and LINACs. In 2001 a patient with medulloblastoma 

was referred to our department. Given his age, height and neurological 

deficit (blind, paraplegic) a reproducible whole CSA treatment could only be 

given supine and an ’ad hoc’ change was required. Given the positive experience 

in 2002 we established a multidisciplinary working group for the change 

in practice after decades of using a prone technique. The technique was successfully 

implemented and with the advent of more sophisticated planning 

methods in conjunction with linac couch developments from 2005 we began 

to CT plan and treat all patients supine. Immobilisation has always been key 

to the technique. In the prone set-up the patient was positioned in the front 

half of a shell, with tattoos along the spine. Because we could see the light 

field junction, alignment was regularly manipulated to make things ’look right’ 

but still required a substantial number of corrections once a verification film 

was obtained. We currently use a vacuum bag and thermoplastic shell, for 

chin and shoulder immobilisation, and raise the knees for a flat back. Improvements 

were seen in many different aspects of the treatment particularly 

in minimising errors. Set-up accuracy of the brain and spine fields is ~1.5mm 

and ~2mm mm respectively. Overall it is far more acceptable for a patient to lie 

face up than down, especially for young children and those treated under GA. 

The change in practice including the use of CT planning and MLC shielding 

rather than individually cast alloy blocks has reduced mould room time and 

time from booking to starting treatment. (40 15 days) Multiple segmented 

beams are now used to create a homogenous dose distribution across the 

length of the spine. The ’feathered edge’ required at the junction between the 

skull and spine is achieved by segmented fields that are all treated on a daily 

basis which has improved the dose distribution as well as accuracy of set-up. 

Verification is undertaken on set on D 1-3 and weekly thereafter. As the light 

field cannot be seen from the posterior spine field with the supine technique, 

a steel ball bearing is placed at the inferior border of the lateral cranial fields 

on the anterior midline and imaged in both planes. The technique has further 

evolved over the last 3 years and we have now a safe and more accurate 

technique compared to the prone set-up using conventional planning which 

is feasible in both adult and paediatric patients. In addition this technique allows 

a safer, less time-consuming data transfer from the TPS to Mosaiq, via 

DICOM. The first patient treated in 2001 remains in a first complete remission. 

517 speaker 

FOCAL IRREVERSIBLE ALOPECIA IN HIGH DOSE RADIOTHERAPY 

FOR BRAIN TUMORS IS AVOIDABLE 

B. Vanstraelen 1 , J. Menten 1 , J. Verstraete 1 

1 UZ LEUVEN, Radiotherapy, Leuven, Belgium 

Introduction: Cortical brain tumors are located near the skull, so hair follicles 

are very close to the irradiation target volume. Doses of 60Gy to the hair follicles 

cause in 80% permanent alopecia. Focal hair loss is one of the stressful 

side-effects in long-term survivors but can be avoided by minimizing the dose 

below 40Gy to the hair follicles without decreasing the tumor control. 

Methods: -In delineating the GTV and subsequent CTV is the inner surface 

of the skull a natural border. 

-Secondly, for the treatment plan, the highest energy (18 MV in our department) 

is used. Due to the larger build-up region "skin sparing effect" the dose 

at the hair follicles is lowerd. 

-The most frequent cause for getting permanent alopecia superficial brain tumor 

irradiation is the overlap on the skin between 3 or more different beams. 

Using at least 3 at the skin non-overlapping beams can solve this problem, 

however more volume of normal brain will be irradiated to low non toxic doses. 

Sometimes inclination of opposing beams is necessary to minimize the region 

of overlap. During the presentation will be demonstrated how this to do. 

-Blocks are individually placed in the tangential fields just to touch the outside 

of the skull to protect the subcutaneous hair follicles from high irradiation 

doses (>40Gy). 

Results: This technique is used for 20 years in our department, but is modified 

in the last 3 years. The cerrobend blocks are replaced by multileaf collimators 

(5 mm) and the localization procedure on the simulator to define 

the beam inclination is skipped and replaced by a virtual simulation after 3D 

CT-scanning. The radiotherapy dose to the hair follicles needs to be below 

40Gy and for the brain there is a constrain for a maximum of 102% if 60Gy 

in 2gy fraction size is prescribed, this to avoid brain necroses. Grade 3 or 4 

post-irradiation alopecia were no longer seen in the long term follow-up (≥ 

20 years) while there is no increase in local recurrences against the inner 

surface of the skull . 

Conclusion: Definite alopecia can be avoided in brain irradiation by using at 

least 3 beams with high energy photons (18MV) if overlap at the skin with ≥3 

fields is avoided. 

Quality aspects of IGRT 

518 speaker 

EUROPEAN INSTITUTE OF RADIOTHERAPY 1ST TASK GROUP 

REPORT, AND SOME GENERAL ASPECTS OF IGRT QA 

S. Korreman 1 , P. Maingon 2 , H. McNair 3 , U. Oelfke 4 , C. Rasch 5 , D. 

Verellen 6 , B. Mijnheer 5 , V. Khoo 7 

1 



2 

CENTRE G-F LECLERC, Radiotherapy Department, Dijon, France 

3 

THE ROYAL MARSDEN HOSPITAL, Department of Radiotherapy, London, 


4 

DKFZ, Dept. of Medical Physics, Heidelberg, Germany 

5 

NKI, Radiotherapy, Amsterdam, Netherlands 

6 

UZBRUSSEL, Radiotherapie, Brussels, Belgium 

7 

THE ROYAL MARSDEN HOSPITAL, Urology Unit, London, United Kingdom 

Background: In mid-2007, the first task group under the auspices of the 

European Institute of Radiotherapy (EIR) was formed to provide a review of 

the current status of 3D CT-based image guided in-room systems and their 

pertinent application for image guidance. This addresses both technical and 

practical issues, and an approximate estimation of work practices including 

work flow issues. 

Material and Methods: The systems of four major vendors of CT-based 

in-room image guidance systems have been specifically evaluated; Elekta, 

Siemens, Tomotherapy and Varian solutions, together with the generic workflow 

processes for system implementation, capabilities and use. Workflow 

evaluation has been performed by sending out a questionnaire to a number 

of clinics in Europe. The clinics were asked to report timing (and comments) 

for processes including image acquisition, reconstruction, analysis and application 

of corrections for prostate and head&neck cancer cases. 

Results: The task group has produced the report "3D CT-based in-room image 

guidance systems: a practical and technical guide" relaying the outcome 

of the group’s work within the subject. The report consists of sections covering 

generic issues of MV and kV CT-based techniques, technical specifications 

of several image guidance systems, as well as user provided information


on the clinical workflow for the selected user cases. 

Conclusions: This report proposes and aims to provide a common platform 

for assessment of the properties of the different systems and their clinical implementation, 

with respect to both technical and workflow issues. This report 

also provides a check list with suggestions for aspects to consider when purchasing 

3D CT-based image guidance systems, as well as for the handling of 

your chosen system. 

519 speaker 

GEOMETRIC QA OF IGRT SYSTEMS 

J. Sykes 1 



There is now a wide range of Image guided radiotherapy systems available 

on the market including ultrasound, orthogonal radiographic and fluoroscopic, 

surface sensors and surface fiducial tracking, helical MV CT and cone beam 

CT both kV and MV. They all have one thing in common, the requirement to 

accurately locate the target or target surrogate in the frame of reference of 

the treatment beam. The geometrical accuracy and reproducibility of the system 

needs to be measured and factored into the design of treatment margins. 

Quality assurance of system geometry is therefore essential both for ensuring 

systematic errors are minimised and for determining the random component 

over time. For nearly all IGRT systems, Quality Assurance (QA) of geometry 

can be divided into three key components: - registration of a single point in 

the imaging system to a single point (MV isocentre) in the treatment system 

- spatial integrity of the imaging system; i.e. rotation, scaling and distortion - 

patient correction e.g. automatic couch translation/rotation. This talk will discuss 

a range of methods for checking system geometry using predominantly 

cone beam CT as an example. The frequency with which these checks should 

be carried out and the tolerance of the check will also be discussed and will 

be dependent on : - the magnitude and impact of any likely geometric inaccuracy 

- the tolerance required for a particular image guided procedure - 

the frequency with which a geometric error is likely to occur. Geometric misalignment 

in Cone Beam CT may also have implications on image quality and 

accuracy of image registration. These will be highlighted with reference to the 

other talks in this session. 

520 speaker 

DOSIMETRIC QA OF IGRT SYSTEMS 

U. Oelfke 1 

1 GERMAN CANCER RESEARCH CENTER (DKFZ), Heidelberg, Germany 


521 speaker 

QUALITY ASSURANCE OF ALIGNMENT AND AUTOMATION FOR 

IGRT 

J. Balter 1 , M. Kessler 1 , R. Kashani 1 , K. Lam 1 , M. Hub 2 


2 DEUTSCHES KREBSFORSCHUNGSZENTRUM (DKFZ), Radiation Oncology, 


The field of radiotherapy has been very successful recently in introducing image 

alignment tools into clinical practice. Not only manual, but automated 

alignment techniques as well are available for use in aiding image-guided patient 

positioning. Furthermore, deformable alignment is being promised and 

potentially delivered to aid positioning and plan modification. With such a 

variety of complex tools being presented to the community, the need is ever 

pressing for standards of practice in documenting, accepting, commissioning, 

and testing these techniques. Directly related is the need for tools and 

related methodologies that can effectively provide a trustworthy testing environment 

for individual users. This talk explores these areas. The nature of 

various alignment methods will be briefly explored and classified (degrees of 

freedom, level of automation, optimization method, figure of merit, final user 

feedback and review). Physical and computational methods of validation will 

be explored, ranging from repeat alignment experiments on generated data 

to physical phantoms and finally observer studies on clinical data. A discussion 

of the impact of uncertainty in alignment will be included, with other 

factors from the control process mentioned in the error budget and influence 

on thresholds and decisions of off-line versus on-line adjustments at various 

levels of complexity. The importance of end-to-end tests, and procedures 

that include the impact of uncertainty in the process, will be included. Current 

efforts of the AAPM in quality assurance of alignment for IGRT will be 

mentioned. 

S 171 

Omics, 4D and PET in radiotherapy for stage I-III 

NSCLC 

522 speaker 

TARGET DEFINITION USING PET-CT FOR LUNG CANCER PA- 

TIENTS 

R. Steenbakkers 1 , I. Fitton 2 , J. Duppen 1 , M. van Herk 1 , C. Rasch 1 



2 GEORGES POMPIDOU EUROPEAN HOSPITAL, Radiology, Paris, France 

Purpose: Currently, PET-CT is considered to be standard of care in the diagnostic 

workup of patients with lung cancer. We wanted to evaluate the impact 

of matched PET-CT on target definition for radiotherapy. 

Materials and methods: Eleven radiation oncologist from five different institutions 

delineated the Gross Tumor Volume (GTV), including pathological 

lymph nodes, of 22 lung cancer patients (stage I IIIB). For the first delineation 

round, they delineated on CT only. For the second delineation round, 

they delineated on a matched PET-CT. The variation in delineation among 

the radiation oncologists was computed in 3-D. All observer computer interactions 

were recorded and analyzed with a tool called ’Big Brother’. 

Results: The addition of PET has a large impact on treated volume, mainly 

due restaging. For all patients, the variation in delineation was reduced from 

1.0 cm (1 SD) for CT only to 0.4 cm for matched PET-CT. The largest reduction 

of the variation in delineation was seen at the tumor - atelectasis region 

(SD 1.9 cm reduced to 0.5 cm). For several patients the addition of PET is 

helpful to distinguish atelectasis from tumor. Unfortunate some patients had 

increased FDG-uptake in atelectasis as well, probably due to inflammation. 

Using PET-CT, radiation oncologists are able to identify more easily pathological 

lymph nodes. Remarkably, in our study 10% of the lymph nodes, which 

revealed increased FDG-uptake, were missed. The addition of contrast enhancement 

for the planning CT is warranted in these cases. Furthermore, for 

patients with tumors mainly surrounded by lung tissue (without lymph nodes), 

the variation in delineation was rather small using CT only (SD 0.4 cm). The 

addition of PET-CT for these patients did not significantly reduce the variation 

(SD 0.3, p =0.2). With the Big Brother tool, we found inappropriate use of 

level and window settings for delineating the GTV and that some radiation 

oncologists did not delineate according protocol. 

Conclusions: Implementing a matched PET-CT has a large impact on target 

volume delineation of lung cancer patients. However, the remaining variation 

in delineation is still large compared to other geometrical uncertainties (setup 

variation and organ motion) and further improvement is warranted. Furthermore, 

for delineating tumors mainly surrounded by lung tissue (without pathological 

lymph nodes) a matched PET-CT seems not essential. 

523 speaker 

STEREOTACTIC BODY RADIOTHERAPY FOR MEDICALLY INOPER- 

ABLE PATIENTS WITH STAGE I NON-SMALL CELL LUNG CANCER. 

AN EARLY REPORT FROM A PROSPECTIVE PHASE II STUDY. 

P. Baumann 1 , J. Nyman 2 , M. Høyer 3 , G. Gagliardi 4 , I. Lax 4 , B. Wennberg 

4 5 6 1 5 7 

, N. Drugge , L. Ekberg , S. Friesland , K. A. Johansson , J. A. Lund , 

E. Morhed 8 , K. Nilsson 9 , N. Levin 10 , M. Paludan 3 , C. Sederholm 11 , A. 

Traberg 12 , L. Wittgren 13 , R. Lewensohn 1 

1 

KAROLINSKA UNIVERSITY HOSPITAL, Department of Oncology and 

Radiotherapy, Stockholm, Sweden 

2 

GÖTEBORG UNIVERSITY, SAHLGRENSKA UNIVERSITY HOSPIT, Department 

of Radiation Oncology, Göteborg, Sweden 

3 

AARHUS UNIVERSITY HOSPITAL, Department of Oncology and Radiotherapy, 


4 

KAROLINSKA UNIVERSITY HOSPITAL, Department of Hospital Radiophysics, 


5 

GÖTEBORG UNIVERSITY, SAHLGRENSKA UNIVERSITY HOSPIT, Department 

of Hospital Radiophysics, Göteborg, Sweden 

6 

MALMÖ UNIVERSITY HOSPITAL, Department of Oncology and Radiother-


apy, Malmö, Sweden 

7 

ST. OLAVS UNIVERSITY HOSPITAL TRONDHEIM, Department of Oncology 

and Radiotherapy, Trondheim, Norway 

8 

UPPSALA UNIVERSITY HOSPITAL AKADEMISKA SJUKHUSET, Department 

of Hospital Radiophysics, Uppsala, Sweden 

9 

UPPSALA UNIVERSITY HOSPITAL AKADEMISKA SJUKHUSET, Department 

of Oncology and Radiotherapy, Uppsala, Sweden 

10 

ST. OLAVS UNIVERSITY HOSPITAL TRONDHEIM, Department of Hospital 

Radiophysics, Trondheim, Norway 

11 

LINKÖPING UNIVERSITY, Department of Oncology and Radiotherapy, 

Linköping, Sweden 

12 

AARHUS UNIVERSITY HOSPITAL, Department of Hospital Radiophysics, 


13 

MALMÖ UNIVERSITY HOSPITAL, Department of Hospital Radiophysics, 

Malmö, Sweden 

Within the Nordic study group of Stereotactic Body Radiotherapy (SBRT) we 

have previously shown an 88% local control with a median dose of 15 Gy 

x 3 in medically inoperable patients with stage I non small cell lung cancer 

(NSCLC). From a prospective phase II study on the same patient category 

we now report on local control, survival and toxicity as related to severity of 

COPD and cardio vascular disease CVD.Sixty patients from Sweden, Norway 

and Denmark entered the study from Aug. 2003 to Sept. 2005. Fiftyseven 

patients with T1 (65%) and T2 (35%) and a median age of 75 years 

(range 59-87 y) were evaluable. At baseline mean FEV1% was 64% and 

mean Karnofsky index was 80. The patients were further subdivided in four 

groups according to severity of COPD (GOLD criteria). SBRT was delivered 

in the Stereotactic Body Frame (SBF) with 15 Gy x 3 to the 67% isodose of the 

periphery of the PTV.At a median follow-up of 24 months the local control rate 

was 96%. Nine patients (16%) had local failure, regional- or distant metastases. 

Twenty patients (35%) died during follow-up and in 20% (4/20) of the 

cases death was related to lung cancer. The 1- and 2-years overall survival 

was 86% and 65% respectively. No grade 4 or 5 toxicity was reported. Grade 

3 toxicity was seen in 12 patients (21%). There was no significant decline of 

FEV1% during follow up independent of GOLD status. No decrease in performance 

status could be seen in the whole patient group but the CVD group 

had a significantly larger decrease than the COPD group. Final survival and 

response data will be presented at the time of the meeting.SBRT for stage I 

NSCLC results in a favourable local control rate with acceptable toxicity, even 

for the patients with highly impaired medical condition due to COPD. 

524 speaker 

AN IMMUNE RESPONSE ENRICHED 72-GENE PROGNOSTIC 

PROFILE FOR EARLY STAGE NON-SMALL-CELL LUNG CANCER 

P. Roepman 1 , J. Jassem 2 , E. Smit 3 , T. Muley 4 , J. Niklinski 5 , T. van 

de Velde 6 , A. Witteveen 7 , A. Floore 7 , S. Burgers 6 , G. Giaccone 8 , M. 

Meister 4 , H. Dienemann 4 , M. Skrzypski 2 , M. Kozlowski 5 , W. Mooi 3 , N. 

Zandwijk 6 

1 AGENDIA, Department of Bioinformatics, Amsterdam, Netherlands 

2 MEDICAL UNIVERSITY OF GDANSK, Poland 

3 VU MEDICAL CENTER, Amsterdam, Netherlands 

4 THORAXKLINIK UNIVERSITY OF HEIDELBERG, Heidelberg, Germany 

5 MEDICAL UNIVERSITY OF BIALYSTOK, Bialystok, Poland 

6 NETHERLANDS CANCER INSTITUTE-ANTONI VAN LEEUWENHOEK HOSPI- 

TAL (NKI-AVL), Amsterdam, Netherlands 

7 AGENDIA, Amsterdam, Netherlands 

8 NATIONAL CANCER INSTITUTE, NATIONAL INSTITUTES OF HEALTH,, 

Bethesda, USA 

Background: Current staging methods are imprecise for predicting prognosis 

of early stage non-small-cell lung cancer (NSCLC). We aimed to develop 

a gene expression profile or stage I and II NSCLC, allowing identification of 

patients with a high risk of disease ecurrence within 2-3 years after initial diagnosis. 

Methods: We used whole-genome gene expression microarrays to analyze 

frozen tumor samples from 172 NSCLC patients (pT1-2, N0-1, M0) from 5 

European institutions, who had undergone complete pulmonary resection. 

Median follow-up was 89 months (1.2 389) and 64 patients developed a recurrence. 

A random two-thirds of the samples were assigned as the training 

cohort with the remaining samples set aside for independent validation. Cox 

proportional hazards models were used to evaluate the association between 

expression levels of individual genes and patient recurrence-free survival. A 

nearest mean analysis was used to develop a gene-expression classifier for 

disease recurrence. 

Results: We have developed a 72 gene expression prognostic NSCLC classifier. 

Based on the classifier score, patients were classified as either high 

or low risk of disease recurrence. Patients classified as low-risk showed a 

significantly better recurrence-free survival in both the training set (p


surgical centres, pancreatic cancer biology, and its resistance to conventional 

treatment modalities. Until recently, cancer researchers had little regard for 

the implications of tumour cell heterogeneity and focused mainly on the tumour 

as a whole. A better understanding of cancer initiation, progression and 

recurrence has led to the hypothesis that tumours are steered by a small subset 

of ’tumour-driving cells’ or ’tumour-initiating cells’ generically named cancer 

stem cells (CSC). Activation or reactivation of developmental signalling 

cascades, increased DNA-repair and anti-apoptotic mechanisms and expression 

of multidrug efflux transporters in these fuelling CSC may explain at least 

partially why PDAC is resistant to standard multimodal therapy. Conventional 

chemotherapy and radiotherapy affect rapidly dividing pancreatic cancer cells 

that constitute the tumour bulk but fail to target the CSC that drive tumorigenesis 

and metastasis. Indeed, there is growing evidence to support a crucial 

role for CSC in PDAC. In the future, any treatment designed to eradicate 

pancreatic cancer needs to eradicate all the CSC without hampering the essential 

regeneration capacity of normal tissue stem cells. Further exploration 

of this close encounter between stem cell biology and cancer biology has the 

potential to revolutionize pancreatic cancer therapy in the near future. 

527 speaker 

WHY NOT PREOPERATIVE CHEMO-RADIATION? 

K. Haustermans 1 

1 LEUVEN CANCER INSTITUTE, UZ LEUVEN, Radiation Oncology, Leuven, 

Belgium 

Adenocarcinoma of the pancreas is a devastating disease. Only approximately 

20 % of the patients are operable at the time of diagnosis. Median 

survival of this selected patient group is only 12 months. Patients die of both 

locoregional recurrence and distant metastasis. Patterns of relapse are important 

when considering adjuvant therapy. In a recent study, local recurrence 

with or without distant metastasis occurred in 41% of patients who underwent 

surgery alone and distant metastasis was diagnosed in 49% [1]. This failure 

pattern highlights the need for optimal surgery and evaluation of adjuvant 

treatment strategies, which include chemoradiation or chemotherapy. The 

risk of subclinical metastasis at the time of primary surgery prompted clinicians 

to initiate studies in which chemoradiation is given preoperatively. In 

this way, patients with disseminated disease at the time of re-staging after 

chemoradiation will not be subjected to major surgery. Resectability rate can 

be improved thanks to downstaging and downsizing caused by the preoperative 

treatment. Also from the biological point of view preoperative chemoradiation 

has the advantage of a better oxygenated tumor bed compared to the 

post-operative setting. Moreover, in a multimodal approach it is always better 

to keep the most toxic treatment, which is for these patients surgery, until the 

end. For radiation oncologists it is easier to delineate the GTV and CTV in 

the preoperative setting compared to the post-operative setting as the tumor 

is still in place. Less normal tissue toxicity due to the radiation can thus be 

expected. The optimal combination schedule is a matter of discussion. Large 

irradiated volumes as well as large doses per fraction preclude the administration 

of full doses of drugs due to the risk of toxicity. Moreover, these patients 

have a limited life expectancy which emphasizes the need for short radiation 

schedules with minimal toxicity. Because of the large percentage of patients 

with disseminated disease the improved locoregional control achieved with 

preoperative chemoradiation followed by surgery will translate in only a small 

survival advantage. Therefore, more effective systemic agents are needed 

to maximize radiation sensitisation and to treat microscopic extra-pancreatic 

disease. Until today, the use of neo-adjuvant strategies in the preoperative 

setting in potentially resectable tumors remains experimental. In a promising 

phase II study, 86 patients were treated preoperatively with gemcitabine 

plus radiotherapy 10 times 3 Gy [2]. Seventy-one patients underwent surgery 

and 74% of them had a resectable tumor and 54% a pathological response. 

Median survival in resected patients was 36 months versus 7 months in nonresected 

cases. Randomized studies are necessary to confirm these promising 

results. 

1. Oettle H, Post S, Neuhaus P et al. Adjuvant chemotherapy with gemcitabine 

vs observation in patients undergoing curative-intent resection of pancreatic 

cancer: a randomized controlled trial. JAMA 2007; 297: 267277. 

2. Wolff R, Evans D, Crane C et al. Initial results of preoperative gemcitabine 

based chemoradiation for resectable pancreatic adenocarcinoma. Proc Am 

Soc Clin Oncol 2002; 21: 130a (Abstr 516). 

528 speaker 

WHY NOT POSTOPERATIVE CHEMO-RADIATION? 

J. Van Laethem 1 

1 CUB HÔPITAL ERASME, Brussels, Belgium 


Evidence based IMRT 

529 speaker 

OPTIMISATION AND DEVELOPMENT OF CLASS SOLUTIONS 

C. De Wagter 1 , W. De Gersem 1 , W. De Neve 1 


S 173 

Class solutions can be defined as the specialised methodologies to plan 

and deliver advanced radiation treatments to specific anatomical sites. The 

anatomical diversity of both PTV and organs at risk within the human body, in 

combination with the various dosimetric objectives and constraints, lead to a 

wide range of geodosimetric demands to which the class solution approach is 

more practical than any general all-round inverse-planning methodology. This 

definition implies much more than a set of planning parameters that is on the 

average acceptable for every patient involved, as is sometimes alluded to 

in literature. Class solutions streamline the planning process and, although 

that they may internally contain inverse planning techniques, they offer the 

ease and flexibility of forward treatment planning. In addition, class solutions 

improve the delivery efficiency and importantly for comparative studies ensure 

that the patients are treated in similar ways. Notwithstanding the fact that 

class solutions may be considered as stripped down full optimisation planning 

methodologies, they have enough flexibility and intelligence incorporated to 

cover variations over a sufficiently wide range of patients. The importance 

of class solutions has been recognized also by treatment planning system 

(TPS) vendors. Although the use of class solutions may be considered as to 

"mimic" dosimetrists, their optimisation and validation is work for experienced 

professionals. For the development and optimisation of class solutions one 

best follows a hierarchy with three taxonomic levels: orders (highest), families 

and species (lowest). Classification criteria for class solution orders (1) are irradiation 

modality (photons, particles) and delivery technique (IMRT, IMAT, tomotherapy, 

&). Criteria at the family (2) level include i) concepts as forward or 

inverse planning; ii) type of dosimetric objectives (physical or biological) and 

constraints in combination with the organ characteristics (parallel or serial architecture, 

moving position, &); iii) beam arrangement; iv) conformal therapy 

or conformal avoidance; v) bixel or aperture based method. The parameterisation 

or commissioning of such a generic family (2) then leads to class 

solution species (3) that are specific for certain anatomical sites and dose 

prescriptions. As a matter of fact, a same anatomical site can be planned 

using different families and thus species of class solutions. This approach 

allows dosimetric intercomparison studies that, when conducted in an "evolutionary 

framework", are components of evidence-based IMRT. The taxonomy 

of the class solutions currently implemented at GUH will be presented and 

discussed. 

530 speaker 

BREAST INTENSITY MODULATED RADIOTHERAPY (IMRT) AND 

CLINICAL BENEFIT: WHAT IS THE EVIDENCE? 

C. Coles 1 

1 CAMBRIDGE UNIVERSITY HOSPITALS NHS FOUNDATION TRUST, Oncology 

Centre, Cambridge, United Kingdom 

Introduction There have been numerous reports of improved dose homogeneity 

with intensity modulated radiotherapy (IMRT), compared with standard 

wedged tangential breast radiotherapy. It has been hypothesised that 

this improvement in dose distribution will translate into a reduction in acute 

and late normal tissue toxicity. However, this requires testing within welldesigned 

randomised controlled trials (RCTs). The design and available results 

of these RCTs will be reviewed. Methods Two RCTs of breast IMRT 

versus standard radiotherapy have been published and a third larger trial is 

still in the follow up phase. Between 1997 and 2000, the Royal Marsden 

Hospital (RMH) trial, randomised 306 patients judged as bring at higher than 

average risk of radiation-induced normal tissue toxicity by virtue of breast 

size and/or shape. The primary endpoint was change in breast appearance 

scored from serial photographs at 1, 2 and 5 years. Between 2003 and 

2005, 358 patients were randomly assigned in two Canadian centres. The 

primary endpoint in this RCT was acute radiation induced toxicity. The Cambridge 

Breast IMRT trial has randomised 814 patients with significant dose 

inhomogeneity with standard radiotherapy, between 2003 and 2007. The 

primary endpoint is change in breast appearance scored from serial photographs 

at 2 and 5 years. Results In the RMH trial, 240 (79%) patients with 

5-year photographs were available for analysis. Change in breast appearance 

was identified in 71/122 (58%) allocated standard 2D treatment compared 

to only 47/118 (40%) patients allocated 3D IMRT. The control arm patients 

were 1.7 times more likely to have a change in breast appearance than the 

IMRT arm patients (95% confidence interval 1.2-2.5, p=0.008). No significant 

differences between treatment groups were found in patient reported breast 

discomfort, breast hardness or quality of life. In the Canadian trial, 31.2% 

developed moist desquamation during or up to 6 weeks after their radiation 

treatment with IMRT, compared with 47.8% with standard treatment experiencing 

(p=0.002). The use of IMRT did not correlate with pain and quality of 

life, but the presence of moist desquamation did significantly correlate with 

pain (p=0.002) and reduced quality of life (p=0.003). The Cambridge Breast


IMRT trial is as yet unreported. Conclusion There is limited RCT evidence 

that IMRT reduces acute and/or late radiation-induced normal tissue toxicity 

compared with standard breast radiotherapy. It remains to be seen whether 

the larger Cambridge Breast IMRT trial will support this data. It is possible 

that the patient’s genetic profile may be as important as physical dosimetry 

in determining the individual variation in normal tissue response to radiation. 

Blood DNA samples from patients in the Cambridge trial are under investigation 

for this purpose within a multicentre UK study, RAPPER Radiogenomics: 

Assessment of Polymorphisms for Predicting the effects of Radiotherapy. . 

531 speaker 

PROSTATE CANCER AND IMRT 

D. Routsis 1 

1 ADDENBROOKE’S HOSPITAL, Cambridge, United Kingdom 


532 speaker 

PRELIMINARY RESULTS FROM CLINICAL IMRT TRIALS 

C. Nutting 1 

1 ROYAL MARSDEN NHS FOUNDATION TRUST AND INSTITUTE OF CANCER 

RESEARCH, Sutton, United Kingdom 

IMRT has been in routine clinical practice in some institutions for approaching 

10 years, and its clinical implementation has been very rapid, particularly in 

North America.So far, very few randomised clinical trials of IMRT have been 

reported, with many clinicians apparently happy to accept at face value the 

potentially improved dose distributions and the data from Phase II clinical trial 

publications.This presentation will review the evidence base for clinical IMRT, 

concentrating on head and neck, pelvic, breast, and other tumour sites. 

Radiation-induced secondary cancer: revisiting 

the field 

533 speaker 

RADIATION-INDUCED SECONDARY CANCERS ; THE CLINICAL 

EXPERIENCE 

K. R. Trott 1 

1 ST. BARTHOLOMEW’S MEDICAL COLLEGE, London, United Kingdom 


534 speaker 

MODELS TO PREDICT RADIATION INDUCED CANCER AT LARGE 

DOSE 

U. Schneider 1 

1 STADTSPITAL TRIEMLI, Radiation Oncology and Nuclear Medicine, Zurich, 

Switzerland 

The dose-response relationship for radiation carcinogenesis up to one or two 

Gy has been quantified in several major analyses of the atomic bomb survivors 

data. Recent papers have been published, for example, by Preston 

et al and Walsh et al. This dose range is important for radiation protection 

purposes where low doses are of particular interest. However, it is also important 

to know the shape of the dose-response curve for radiation induced 

cancer for doses larger than one Gy. In patients who receive radiotherapy, 

parts of the patient volume can receive high doses and it is therefore of great 

importance to know the risk for the patient to develop a cancer which could 

have been caused by the radiation treatment. In addition, the health risk to 

astronauts from space radiation is recognized as one of the limiting factors 

for long-term space missions. During solar events astronauts can receive 

doses which are larger than one Gy. There is currently much debate concerning 

the shape of the dose-response curve for radiation-induced cancer. 

It is not known whether cancer risk as a function of dose continues to be 

linear or decreases at high dose due to cell killing or levels off due to, for 

example, a balance between cell killing and repopulation effects (see Figure). 

The work presented here, aims to clarify the dose-response shape for 

doses larger than one Gy. In this dose range, data are available from the 

atomic bomb survivors from Hiroshima and Nagasaki, although the data pertaining 

to doses of over 4 Gy have not usually been included in previous 

analyses, due to the associated large uncertainties. In addition, data are 

available from radiotherapy patients who were irradiated with localized doses 

of up to around 70 Gy. The aim of this report is to give an literature overview 

of the possible dose-response relationship for radiation induced solid cancer 

for radiotherapy doses.Still many problems and uncertainties are involved and 

very little is currently known about the shape of dose-response relationships 

for radiation-induced cancer in the radiotherapy dose range. However it is 

important to acquire more information in this area. 

535 speaker 

ICRP/ICRU RECOMMENDATIONS 

J. M. Cosset 1 , A. Wambersie 2 , C. Cousins 3 

1 

VICE-CHAIRMAN, ICRP COMMITTEE 3, Belgium 

2 

ICRU, Belgium 

3 

CHAIRWOMAN, ICRP COMMITTEE 3, Belgium 

While a number of new techniques of Radiotherapy, such as IMRT, have recently 

emerged, and are rapidly introduced into routine practice, a few authors 

have underlined possible disadvantages of some modern technologies. 

With the increase in the numbers of beams and also the increase in the number 

of monitor Units ( MU), more healthy tissues receive low doses, with, 

consequently, the theoretical potential to increase the risk of secondary induced 

cancers in those areas. Some authors have calculated that in some 

instances, in particular with IMRT, this risk could be doubled.ICRP and ICRU 

therefore decided to elaborate a common document aiming at evaluating the 

risks of second cancers related to the newly introduced techniques, and aiming 

at proposing solutions to manage this risk.The document will be based on 

the available clinical data, taking advantage of the recent NIH 2006 publication 

" New malignancies among cancer survivors". Clinical experience shows 

that most of the induced cancers occur in or close to the high-dose treatment 

volume ( and not in the low-dose regions). Clinical data also emphasize the 

role of age, with children being much more sensitive to the carcinogenic effect 

of ionizing radiations than adults. Last but not least, the relative risks 

tend to be lower in the medical series than in the Japanese bomb survivors, 

an important point if we keep in mind that most risk models are directly derived 

from this last cohort.A second section of the future document will focus 

on the physical characteristics and on the dose distribution achieved by the 

various techniques. We propose to split the dose regions outside the target 

volume into three groups ; "low dose", medium dose" and "high dose". A first 

analysis shows that with most modern techniques, the "low-dose" regions 

are increased, but that in parallel, the "high-dose" regions are decreased, 

with a counterbalance of the risks. Moreover, one must consider here the 

non-negligible scattered dose delivered by the physical wedges, as well as 

the dose delivered by modern IGRT ( Image-guided Radiotherapy).An entire 

section is going to be devoted to the radiobiological aspects , and particularly 

to the analysis of the different risk models, taking into account ( or not ) the 

"competition" at high dose between the mutagenic effect and the cell killing. 

Depending on the model, the second cancer risk can be calculated to be either 

superior with modern techniques such as IMRT, or exactly similar ( with 

an advantage for Protontherapy in most cases ).Recommandations will be 

made to reduce as much as possible the risk of second radio-induced cancers. 

Emphasis will be put on children, since for various reasons the risk of 

developing a radio-induced cancer is much higher in chidren than in adults after 

a given dose of radiation.The ICRP/ICRU document is still in a draft form. 

Of note, close contacts have been developped with other groups working on 

the same topic, such as NCRP.


Treatment plan optimisation 

536 speaker 

MULTI-OBJECTIVE TREATMENT PLAN OPTIMISATION WITH 

RADIOBIOLOGICAL MODELS: PRINCIPLES AND TOOLS 

A. Hoffmann 1 

1 RADBOUD UNIVERSITY NIJMEGEN MEDICAL CENTRE, Radiation Oncology, 


Inverse treatment planning of intensity-modulated radiation therapy can be 

considered a multi-objective optimization problem. Multiple conflicting treatment 

plan evaluation criteria are used as objective functions to steer the 

optimization process to a compromise solution for which a sufficiently high 

dose is delivered to the tumor target volume, while surrounding organs at 

risk are spared as much as possible. We focus on two limitations of most 

commercial treatment planning systems: 1) only dose or dose-volume based 

physical criteria are used as objectives, and 2) weighting factors are required 

to balance the objectives involved prior to optimization and thereby form a 

single-objective function as the sum of constituent objective functions. Limitations 

of physical criteria for plan evaluation and optimization have been 

examined before and will be discussed. The potential advantage of biological 

criteria taking into account the radiobiological properties of the tissues 

involved has been acknowledged in the past years. Specifically, criteria 

based on tumor control probability (TCP), normal tissue complication probability 

(NTCP), equivalent uniform dose (EUD) and generalized equivalent 

uniform dose (gEUD) have been considered. We demonstrate the use of a 

tool that is currently available to exploit such criteria for biological evaluation 

and optimization of treatment plans. In particular, its ability for rival plan assessment 

and prescription dose customization in the TCP-NTCP space are 

addressed. Furthermore, the weighted-sum-based a priori decision making 

approach is criticized and the concept of Pareto optimality that allows for a 

posteriori decision making is addressed. We review the current progress 

in multi-objective treatment planning exploiting this concept and focus on two 

important aspects: methods to find Pareto optimal treatment plans and equivalence 

of physical and biological objective functions. The first aspect deals 

with recent developments in techniques to identify the Pareto efficient frontier 

(PEF). Specifically, for optimization problems with convex objective functions, 

algorithms and strategies to generate a representative subset of the (convex) 

PEF are reviewed. The second aspect relates to invariance of the PEF under 

transformations of non-convex criteria like TCP and NTCP. This presentation 

will review a unifying framework of convex multi-objective optimization problems 

that was proposed to identify criterion functions which are truly distinct 

and thus yield different PEFs. Examples of transformations to convexify commonly 

used radiobiological treatment evaluation criteria based on the linear 

quadratic model to account for fractionation effects will be presented. 

537 speaker 

TREATMENT PLAN OPTIMISATION IN BRACHYTHERAPY 

K. Tanderup 1 


Denmark 

Image guided brachytherapy and 3D dose optimisation has been used for 

prostate cancer since the 90’s. In recent years, 3D image guidance has 

rapidly developed for cervix and breast cancer brachytherapy. The dose 

optimisation procedure is mainly guided by dose volume histogram (DVH) 

parameters: V100, D100, D90 for target volumes and D2cc for OAR. However, 

because of the large dose inhomogeneity, parameters indicating the 

dose homogeneity and high dose volumes (V150/V200 or D70/D50) are also 

considered for the target and small absolute volumes for the OAR (e.g. 0.1 

cm3, 1 cm3) Different dose optimisation tools are available: manual, graphical 

(called "drag and drop of isodoses") and inverse optimisation. With manual 

optimisation, dwell times are adjusted manually until DVH constraints are 

fulfilled as closely as possible. This procedure is depending on the dose 

planner and may be time consuming. With graphical optimisation, isodose 

lines are pushed or pulled by the dose planner, while the system calculates 

corresponding dwell times. Inverse planning is a relatively new and promising 

way of fast optimisation that has been developed for HDR brachytherapy 

in prostate cancer and attributed to be useful for clinical practice. Evidence 

for advantages and disadvantages is still awaited for other sites. Since this 

method is guided exclusively by DVH constraints, the major question is how 

far the DVH constraints selected will meet the physical and clinical demands. 

The pitfalls discussed so far are mainly large deviations from standard loading 

patterns. It has to be kept in mind that brachytherapy based on standard 

loading patterns as used for decades in clinical practice has been comprehensively 

correlated to clinical outcome. It has been shown in several treatment 

planning studies that dose optimisation can significantly improve certain DVH 

parameters for both tumour and organs at risk. The potential amount of increase 

in target dose seems to be in the range of 10-20%. The benefit in OAR 

DVH parameters can be even more pronounced, depending on the individual 

topography. The clinical potential of dose optimisation is that this change in 

dose and volume, if carefully applied and based on the existing clinical expe- 

S 175 

rience, may lead to improved local control and/or decreased morbidity. This 

potential, however, depends to a large degree on the different clinical situations 

and the different clinical applications, e.g. for gynaecology, breast and 

prostate brachytherapy. 

538 speaker 

ROBUST BIOLOGICALLY BASED IMRT OPTIMISATION INCLUDING 

UNCERTAINTIES OF INPUT PARAMETERS 

M. Patriksson 1 , C. Cromvik 1 

1 CHALMERS UNIVERSITY OF TECHNOLOGY, Department of Mathematical 

Sciences, Göteborg, Sweden 

Robustness is an essential part of an optimal IMRT plan. Biological variations, 

positioning uncertainties, and setup errors all contribute to uncertainties 

in a treatment plan.A model for the optimal plan should incorporate uncertainty 

modelling so that it is less sensitive to variations, which otherwise could 

have a large impact on the quality of the plan. The traditional approach to deal 

with uncertainties is to set up a stochastic model, where certainparameters 

are assumed to be stochastic with a certain probability distribution. However, 

it is often the case that the probability distribution is unknown; for example, 

the true mean and variance might be unknown for a normal distribution, and 

the natural question is then what effect this may have on an optimal plan.We 

will present what we mean by robustness and outline a mathematical theory 

which covers many models for IMRT planning optimisation. We will show 

which type of models are robust, both convex and nonconvex ones, and we 

will present some numerical results showing the effect of usinga robust IMRT 

optimisation model in contrast to a traditional one.

S 176 PROFFERED PAPER THURSDAY, SEPTEMBER 18, 2008 


Treatment of prostate cancer 

539 oral 

INTERIM RESULTS FROM A RANDOMISED TRIAL COMPARING 

THE BLADDER VOLUME CONSISTENCY ACHIEVED WITH TWO 

BLADDER-FILLING PROTOCOLS IN PROSTATE CONFORMAL 

RADIOTHERAPY. 

L. Mullaney 1 , L. A. Cleary 1 , E. O’Shea 1 , J. Armstrong 1 , T. O Hara 2 , L. 

O’Neill 3 , P. Thirion 1 

1 

ST. LUKES HOSPITAL, Radiotherapy Department, Dublin, Ireland Republic 

of 

2 

ST. LUKES HOSPITAL, Dublin, Ireland Republic of 

3 

ST. LUKES HOSPITAL, Department of Physics, Dublin, Ireland Republic of 

Purpose: As a consequence of more conformal treatment techniques in 

prostate radiotherapy, dose distributions are increasingly conformed to target 

volumes and become more sensitive to treatment uncertainties, such as 

organ motion. Hollow organs present difficulties because of their variation in 

volume and position according to differences in filling. The optimal bladderfilling 

instructions for prostate patients remain to be determined. The aims 

of this trial are to compare the current institutional bladder-filling instructions 

(1080ml H20, 30 mins delay - Arm A) to instructions that might be less demanding 

on patients (540ml H20, 30 mins delay Arm B) in terms of consistency 

of bladder volume achieved during radiotherapy treatment; acute GU 

and GI toxicity; patients’ satisfaction and quality of life; and staff satisfaction. 

Materials: n = 220 radical prostate patients. Bladder volume measurements 

are obtained using the BladderScan TM Instrument (BVI), immediately prior to 

obtaining the planning CT scan and verification and approximately twice during 

each week of treatment. The bladder volumes obtained during treatment 

are compared with the BVI volume obtained at the planning CT scan. 

Results: Interim analysis on the first 50 patient to complete RT found that 

the CT bladder volumes were significantly less than the treatment volumes 

for both arms (Arm A(6 cups) p=0.02; Arm B(3 cups) p=0.001). Verification 

bladder volumes were not significantly different from treatment volumes for 

both arms (Arm A, p=0.12; Arm B, p=0.98). Treatment bladder volumes were 

relatively consistent for individual patients on both Arms. Toxicity showed no 

significant difference between both Arms, except for dysuria, where the incidence 

was higher in Arm A. Median comfort scores are significantly higher 

(more comfortable) for patients in Arm B, p=0.026. A possible reason for 

this inconsistency between planning CT, verification and treatment bladder 

volumes may be due to a pre-hydration letter that is sent to patients prior to 

their CT appointment. This letter requests patients to pre-hydrate i.e. to drink 

approximately 2/3 l of H2O daily, for 3 days prior to their planning CT appointment. 

This may have resulted in the patients having large bladder volumes 

at time of CT and subsequently smaller volumes at time of verification and 

treatment. Patients no longer receive any pre-hydration instructions prior to 

appointments. 

Conclusions: Our initial results showed that patients are not achieving consistent 

bladder volumes between planning CT and treatment. Changes on 

treatment from planning CT bladder volume have dosimetric consequences 

that may impact on normal tissue complication probability. The change in 

hospital policy to remove the pre-hydration letter may result in increase consistent 

between planning CT and treatment. Results from this further analysis 

will also be available for ESTRO 27. 

540 oral 

CONFORMAL PROSTATE RADIOTHERAPY:HOW HAS THE ROU- 

TINE USE OF CONE BEAM CT INFLUENCED CLINICAL PRACTICE? 

H. Summers 1 , S. Stanley 1 , D. Green 1 , J. Sykes 2 , A. Henry 3 

1 

ST JAMES’S INSTITUTE OF ONCOLOGY, Radiotherapy, Leeds, United 

Kingdom 

2 

ST JAMES’S INSTITUTE OF ONCOLOGY, Medical Physics, Leeds, United 

Kingdom 

3 

ST JAMES’S INSTITUTE OF ONCOLOGY, Clinical Oncology, Leeds, United 

Kingdom 

Purpose: To analyse the impact of the introduction of routine cone beam CT 

(CBCT) off-line imaging protocols in prostate radiotherapy and identify factors 

to help select at planning which patients may benefit from CBCT instead of or 

in addition to MV portal imaging. 

Materials: A retrospective review of the CBCT images of 32 patients receiving 

conformal prostate radiotherapy (55Gy in 20 daily fractions). Patients received 

information on diet and some received regular laxatives prior to treatment. 

CBCTs were acquired off-line fractions 1-3 and then once weekly (6 

planned CBCT/ patient). Images were reviewed by a clinician with a treatment 

radiographer. Bone and CTV set up errors (SUEs) were recorded every fraction 

and population averages calculated. AP rectal diameters were measured 

at the superior, isocentre and inferior planes. Interventions included isocentre 

shifts (if systematic CTV SUEs > 5mm), giving patient further diet advice or 

laxative. Fybogel (bulking agent) was prescribed if random changes in rectal 

distension seen. The intervention rate was assessed. 

Results: Using CBCT the mean CTV population SUEs were < 3mm in all directions. 

AP displacements accounted for 90% of CTV SUEs with 76% seen 

in the anterior direction. CTV SUE exceeded bone SUE for 59% of patients.In 

total 226 CBCTs were acquired (192 planned) resulting in 86 changes in patient 

management. 75% of imaged fractions resulted in intervention. The 

intervention rate was greater for treatments including seminal vesicles vs. 

prostate alone. If bony SUEs only had been used only 19% of patients would 

have required an intervention. The population mean AP rectal diameter at the 

isocentre was 4.2cm. Larger rectal diameter was not directly proportional to 

larger CTV SUE but differences in diameter > 1cm between superior, isocentre 

and inferior levels were associated with greater CTV errors. Sagital rectal 

shapes at planning scan were categorised into Pyramid, Inverse Pyramid, Diamond, 

Hourglass and Regular. Inverse pyramid and diamond shapes were 

associated with greater CTV SUEs and could be used at planning to identify 

those patients who would benefit most from CBCT. 

Conclusions: The workload and intervention rate increased with CBCT compared 

to standard 2-D approaches but did allow more accurate treatment 

delivery. Patients who may benefit from CBCT imaging can be identified at 

planning scan by the size and sagital shape of the rectum. Treatments to the 

prostate and seminal vesicles are subject to more error than prostate alone 

and also may benefit from CBCT imaging. 

541 oral 

PROSTATE ROTATION DETERMINED FROM DAILY IN-ROOM 

COMPUTERISED TOMOGRAPHY (CT) IMAGES. 

R. Owen 1 , T. Kron 2 , F. Foroudi 3 , J. Cox 4 

1 

PETER MACCALLUM CANCER CENTRE, Radiation Therapy Services, 

Melbourne, Australia 

2 

PETER MACCALLUM CANCER CENTRE, Department of Physical Sciences, 


3 

PETER MACCALLUM CANCER CENTRE, Department of Radiation Oncology, 


4 

UNIVERSITY OF SYDNEY, School of Medical Radiation Sciences, Sydney, 

Australia 

Purpose: To determine the rotation of the prostate in the sagittal, transverse 

and coronal planes using implanted fiducial markers and in room computed 

tomography (CT) images. 

Materials: Daily in treatment room CT (Siemens Primatom TM ) images (mean 

number per patient = 34) of 3.0mm slice thickness and pitch 1.5 (512 X 512 

matrix, 50cm FOV) were acquired for 10 patients during their radiotherapy 

treatment for prostate cancer. Each patient had 3 fiducial markers implanted 

into the prostate apex and left and right lobes. The CT scans were evaluated 

after correction of the patient position to ≤2.0mm of the planned position. The 

coordinate locations of the 3 markers were identified relative to the centre of 

volume (CoV) coordinate of the prostate contour. Each patient’s data set was 

assessed individually. Where possible the marker in the apex of the prostate 

was used as the pivot point of rotation along each axis. The coordinates of 

the other 2 markers in the corresponding dimension (eg. for rotation along the 

sagittal plane the AP and SI coordinates are required) were averaged and the 

degree of rotation was calculated using trigonometry. Prostate rotation was 

computed 1) relative to the planning CT scan and 2) relative to the average 

rotation found in the first 5 fractions (n= 6 including the planning CT scan). 

Results: A total of 341 CT images were evaluated. The group systematic 

rotational error was 7.8 ◦ in the sagittal and 3.8 ◦ and 0.9 ◦ in the transverse 

and coronal planes respectively. This error was reduced to -1.4 ◦ and -2.1 ◦ 

in the sagittal and transverse planes respectively when the average rotation 

of the first 5 treatment fractions was used as the reference. Rotation in the 

coronal plane increased from 0.8 ◦ to -3.3 ◦ . For 2 patients, the rotation in the 

sagittal plane varied by more than 30 ◦ from planning CT and in 4 patients the 

rotation in this plane was ≤5.0 ◦ . 

Conclusions: Considerable rotation of the prostate exists. Information from 

a single CT scan does not adequately reflect prostate rotation during a course 

of radiation. A systematic correction based on the average of the first 5 fractions 

reduced the rotation error of the prostate for subsequent treatment fractions. 

Adapting the treatment plan to reflect this could potentially increase 

precision and save time between image acquisition and treatment delivery 

due to complex corrections that may be required at each treatment session. 

542 oral 

DOSIMETRIC ANALYSIS OF TREATMENT PLAN DEGRADATION 

AFTER LARGE SHIFT CORRECTIONS DURING IMAGE-GUIDED 

RADIATION THERAPY (IGRT) FOR THE TREATMENT OF PROSTATE 

CANCER. 

S. Merrick 1 , J. Wong 1 , C. W. Cheng 1 , J. Gao 1 

1 MORRISTOWN MEMORIAL HOSPITAL, Radiation Oncology, Morristown, NJ, 

USA 

Purpose: The use of image guided radiation therapy (IGRT) to correct for 

day-to-day systematic setup errors is essential to minimize the dose variation

THURSDAY, SEPTEMBER 18, 2008 PROFFERED PAPER 

to the treatment target. Many studies have previously shown these variations 

with and without IGRT correction. We now investigate the dose variations 

to the surrounding normal structures after IGRT correction. With regards to 

large shifts of the isocenter, the initial intensely-modulated radiation therapy 

(IMRT) calculations may no longer be applicable because IMRT delivers precise 

amounts of dose with small segmented fields based on fixed anatomical 

locations. 

Materials: IGRT CT scans from prostate cancer patients treated with external 

beam IMRT were compiled and examined. Our IGRT system is comprised 

of a linear accelerator with an in room diagnostic CT-on-rails attached to the 

same treatment table. Patients with final shift corrections ranging in magnitude 

from 5mm to 15mm in the anterior / posterior direction were reviewed. 

Results were analyzed to determine the variations between the initial treatment 

plan calculations versus the original treatment plan superimposed and 

recalculated on the daily IGRT CT scans with the appropriate shift implemented. 

Results: Even with large shift corrections (10mm or more), neither the PTV 

coverage nor mean dose to the PTV was significantly affected with the largest 

difference being 2 3%. In addition, the coverage to the prostate gland did not 

change significantly regardless of the resulting shift magnitude from IGRT. 

However, rectal dose was significantly affected with mean dose differences 

ranging from 15 25% in severe cases. These differences also increased as 

shift magnitude increased and were additionally magnified with large changes 

in treatment planning parameters such as depths and effective path lengths. 

These existing changes were random and non-specific to any one single parameter, 

but the overall dosimetric variations for the rectum were significantly 

affected, particularly with shifts greater than 10mm in the AP/PA direction. 

Conclusions: The positional changes of the target, normal tissue, and differences 

in beam parameters taken individually do not cause significant breakdowns 

in the original treatment plan, but these changes taken as a whole 

and compounded, result in dramatic DVH degradation. To our knowledge, 

this is the first report of dosimetric degradation of initial treatment plans to 

the surrounding normal structures after IGRT corrections. These changes in 

dosimetry may be critical, especially when clinicians have based their estimates 

of current or future side effects/complications on the initial treatment 

plan DVH. As such, with large shifts to the isocenter and positions of normal 

tissues surrounding the target, mere IGRT isocentric corrections may not 

be adequate and further consideration for some type of re-planning maybe 

needed. 

543 oral 

RADIOTHERAPY WITH SIMULTANEOUS INTEGRATED BOOST 

AS A TREATMENT FOR PROSTATE CANCER WITH A MAGNETIC 

RESONANCE (MR) DETECTED INTRA-PROSTATIC LESION (IPL): A 

PLANNING STUDY OF IMAT VERSUS IMRT. 

B. Speleers 1 , W. De Neve 1 , C. De Wagter 1 , F. Jacobs 1 , G. Villeirs 2 , G. 

De Meerleer 1 , A. Van Greveling 1 , V. Fonteyne 1 


2 GHENT UNIVERSITY HOSPITAL, Radiology, Gent, Belgium 

Purpose: To compare 4 different planning techniques for patients with localized 

prostate cancer presenting with a MR-detected IPL. 

Materials: This planning study involves 12 patients. All of them had a MR or 

MRI-spectroscopy detected IPL. For treatment planning, the following anastructs 

were delineated on CT-images: 1. IPL, CTV (prostate + seminal vesicles). 

2. rectum, sigmoid colon, bladder and femoral heads. The PTV was 

created with a 4 mm isotropic margin around the CTV. The plans were optimised 

by GRATIS R○(Sherouse Systems Inc.chapel hill,NC,USA) in order to 

achieve a median dose on the IPL, CTV and PTV of 86, 78 and 76 Gy respectively, 

given that the maximal dose on the rectum did not exceed 76 Gy. 

For each patient, 4 different planning techniques and 2 different photon energy 

levels (6 and 18 MV) were compared, resulting in 8 treatment plans. We 

compared 3 IMRT techniques with SB-IMAT. The IMRT plans consisted of 

3 (0 ◦ -116 ◦ -244 ◦ ; IMRT_3), 5 (0 ◦ -45 ◦ -90 ◦ -225 ◦ -270 ◦ ; IMRT_5) or 7 fields 

(20 ◦ -70 ◦ -120 ◦ -170 ◦ -210 ◦ -260 ◦ -310 ◦ ; IMRT_7). Dose volume histograms 

were used to compare treatment plans. Physical and biological (NTCP) endpoints 

(see Table) were evaluated using a mixed model ANOVA and post-hoc 

Scheffe tests. Planning technique and photon energy were used as fixed 

factors. Patient ID was used as a random factor. 

Results: There was no significant difference between 6 and 18 MV photons 

for the same planning technique. For CTV and IPL Dmin, Dmed and Dmax 

were significantely higher for IMAT compared to the IMRT plans (p


Symposium 

Reliability of IGRT 

545 speaker 

RELIABILITY OF THE BONY ANATOMY IN IMAGE-GUIDED 

STEREOTACTIC RADIOTHERAPY 

M. Guckenberger 1 , M. Flentje 1 

1 JULIUS-MAXIMILIANS UNIVERSITY, Department of Radiation Oncology, 

Würzburg, Germany 

Current standard for verification of patient positioning is electronic portal 

imaging using the therapeutic megavolt x-ray beam. Image quality and especially 

soft-tissue contrast is limited as result of the high x-ray energy. Consequently, 

the bony anatomy usually serves as surrogate for the actual target 

unless radio-opaque markers are implanted into or near the target. Since recently, 

in-room kilo-voltage volume imaging is available offering high spatial 

resolution combined with improved soft-tissue contrast making pre-treatment 

verification of the target position itself possible. In high precision radiotherapy 

of cranial and extra-cranial lesions, so-called "frameless" stereotactic radiotherapy 

has been described: the stereotactic system of external coordinates 

is replaced by image-guidance. For some indications a fixed relationship between 

the target and the bony anatomy has been demonstrated. Imageguidance 

matching the bony anatomy is consequently reliable. However, internal 

mobility independent from the bony anatomy has been described especially 

for intra-pulmonary targets and targets located in the upper abdomen. 

In such cases, image-guidance targeting the lesion itself has been shown to 

significantly increase accuracy of treatment. 

546 speaker 

IMAGE-GUIDED VERIFICATION WITH AN EPID IN CINE MODE 

R. Berbeco 1 , F. Hacker 1 , D. Ionascu 1 , S. J. Park 1 , H. Mamon 1 

1 BRIGHAM AND WOMEN’S HOSPITAL AND HARVARD MEDICAL SCHOOL, 


Purpose: During conventional radiotherapy, the location of the patients’ 

anatomy, particularly the tumor, while the treatment beam is on is of primary 

importance. This becomes especially relevant in treatment sites where large 

intra-fraction motion has been observed (upper abdomen and thorax). We 

have demonstrated a method for monitoring the target during irradiation with 

beam’s-eye-view (BEV) imaging, and then using the intra-fraction data to retrospectively 

calculate the delivered dose. This can be done in between each 

fraction and the cumulative treatment dose updated daily. If discrepancies are 

seen between planned and delivered, the treatment may be altered such that 

the delivered distribution converges with the plan. Method and Materials: The 

radiotherapy target is visualized daily during radiotherapy by collecting the 

exit radiation with an electronic portal-imaging device (EPID) in cine mode. 

In between each fraction, the location of the target in the treatment images is 

compared with the reference position from simulation. The in-treatment target 

positions are introduced in the treatment planning software as sub-fields 

representing equal fractions of the original fields’ monitor units. The dose distributions 

from each of the sub-fields are summed to calculate the dose delivered 

each day. This distribution is updated daily to provide the cumulative 

delivered dose distribution. Results: The target position during radiotherapy 

has been recorded and the dose-volume histograms (DVH) for the planned 

and delivered distributions have been calculated for several patients. Delivered 

doses to target and critical structures are generated for each fraction 

and cumulatively. Using the cine EPID method, we have discovered several 

cases of unexpected, non-periodic intra-fraction motion. Note that this intreatment 

monitoring is implemented independently of the setup procedure. 

Therefore, not only is the cine EPID method compatible with IGRT, but also 

it provides an important, independent verification of the target position during 

radiotherapy. Conclusion: The cine EPID method can be used to ensure 

the reliability of IGRT. The delivered dose is calculated using the information 

contained in BEV images acquired during irradiation. By calculating the dose 

actually delivered to the target, we can assess our treatment procedures as 

well as more accurately report clinical results.


547 speaker 

IGRT FOR CERVIX CANCER 

R. Ahmad 1 , M. Hoogeman 1 , L. Bondar 1 , V. Dawtal 1 , S. Quint 1 , I. de 

Pree 1 , J. W. Mens 1 , B. Heijmen 1 

1 ERASMUS MEDICAL CENTER, Radiation Oncology, Rotterdam, Netherlands 

Target volume motion in cervical cancer patients is of the non-rigid type and 

large of magnitude. To encompass the complex movements generous CTVto-PTV 

margins of 1.5 to 2 cm are used. The motion can partly be explained 

by bladder filling changes, and also rectum filling changes that cause position 

and shape variations. To limit internal organ motion, patients are instructed 

to have a full bladder at planning and during each treatment fraction. A full 

bladder also limits side effects, as it helps to push small bowel away from 

the high dose region. However, repeat US bladder scan measurements at 

planning and twice weekly during the treatment showed that it is impossible 

to maintain a full bladder during the treatment course. Besides a reduction of 

76% in bladder volume a large inter-fraction variability was observed of 168 

ml (1 SD).IGRT in cervical cancer patients might reduce the large margins, 

and treatment related morbidity, provided that quick knowledge of the target 

location and shape can be obtained prior to dose delivery. For the complex 

and predominately non-rigid organ motion of the cervix and uterus such quick 

knowledge is hard to obtain. In-room CBCT scanning might facilitate, but softtissue 

contrast is poor due to scatter and bowel motion during acquisition. US 

bladder scanning can be used to obtain an estimate of the bladder volume. 

The hypothesis was tested that for certain patients the bladder volume is a 

predictor for the position of the uterus. CT data of 11 prone treated patients 

were used. The data consisted of a variable bladder filling CT scan series 

acquired at planning and a series after 40 Gy. An observer localized in the 

bone-matched CT scans Points-of-interest (POI), i.e. the uterus tip and polymeric 

markers in the vaginal fornices. A patient-specific prediction model was 

built relating the bladder volume and the position of the POI prior to treatment. 

The predictability of the model was tested using the CT data obtained after 40 

Gy. A large inter-patient variation was observed in the relation between the 

position of the uterus and the volume of the bladder. The range of displacement 

per 100 ml bladder volume change was 0.2 to 1.3 cm (median 0.6 cm). 

The maximum observed displacement ranged from 1.3 to 5.2 cm (median 

3.3 cm). For 9 out of 11 patients the correlation was significant. For patients 

for which the uterus motion was large at planning corrections based on 

the prediction model could potentially reduce the systematic error by 1.8 cm 

(range 0.1-3.6 cm). Tumor regression was the main cause in cases where 

the prediction model was not accurate, which emphasizes the need to perform 

volumetric imaging regularly. Full 3D patient-specific models obtained 

by non-rigid image registration to generate patient specific margins and to 

assist in IGRT for cervical cancer are currently under development. 

Treatment individualization in patients with SCLC 

treated by radiation therapy 

548 speaker 

RADICAL RADIOTHERAPY IN FRAIL AND/OR ELDERLY PATIENTS 

Y. Lievens 1 

1 UNIVERSITAIRE ZIEKENHUIZEN LEUVEN, Department of Radiation 


The ageing of the population of Western countries represents a special challenge 

for cancer care. Elderly patients are often more frail than their younger 

S 179 

counterparts and present with more co-morbidities, necessitating specific attention 

to avoid treatment toxicity. Moreover, the available evidence - typically 

derived from studies where the frail and elderly are underrepresented or even 

excluded - provides poor guidance for the daily practice in these patients. As 

a result, elderly patients are less likely to be adequately staged and frequently 

receive less aggressive, suboptimal treatment.Lung cancer is a common disease 

in the elderly, with small-cell lung cancer (SCLC) accounting for 20% 

to 25% of the total number of cases. Of these, the minority (20%-30%) will 

be diagnosed with loco-regional tumour extension only (defined as limited 

disease, LD), amenable for treatment with curative intent. Based on metaanalyses 

published in the nineties, curative treatment for LD-SCLC combines 

CT with thoracic irradiation (TI) followed by prophylactic cranial irradiation for 

those in complete remission. A major effort should be made to timely integrate 

chemo- and radiotherapy - that is, minimizing overall treatment time 

while ensuring optimal dose delivery - as this has been recognized to be a 

major contributing factor to outcome. Both the early administration of concurrent 

chemo-radiotherapy and the use of hyperfractioned schedules have 

been studied in this context and have shown their merit. Nevertheless, it has 

likewise been suggested that the advantages of shortened overall treatment 

time may only become apparent provided that the total chemotherapy dose 

delivered is not jeopardized. This brings us to the key issue concerning the 

curative treatment of LD-SCLC in the old and frail patient population: can 

we identify those individuals for whom a dose-intensive approach is justified 

and what measures can we take to limit treatment toxicity?In general, age 

is not regarded as a valuable prognostic criterion for outcome or treatment 

tolerability in LD-SCLC. One meta-analysis showed a trend towards worse 

survival after the addition of TI to CT in patients over 70 years of age, possibly 

due to toxicity. Other (mostly retrospective) analyses investigating the 

influence of various prognostic factors on the outcome in SCLC showed conflicting 

results regarding the impact of age on the delivery, tolerance and efficacy 

of TI in the combined modality treatment of LD-SCLC. Biological age 

should therefore be defined individually taking performance status and comorbidities 

into account - if possible supplemented with a complete geriatric 

assessment - in order to guide treatment intensity, rather than an arbitrarily 

established age limit.If judged necessary on the basis of those assessments, 

treatment can then be tailored towards the general condition of the patient, as 

has been reported in a few phase II studies specifically designed for elderly 

patients with LD-SCLC. But whenever possible, an adequate dose-intensity 

should be aimed for. Obviously, supportive measures should be taken appropriately. 

From a technical point of view, all efforts should be made to optimize 

target definition and radiotherapy planning and delivery in order to minimize 

the dose to the critical organs and potentially ensuing side effects. Finally, 

approaches allowing to reduce the treatment volume (such as starting the 

concomitant chemo-radiotherapy regimen after one or two cycles of induction 

chemotherapy, omitting elective nodal irradiation) deserve further evaluation. 

549 speaker 

RADIOTHERAPY IN LIMITED DISEASE SCLC - INCLUDING DOSE, 

FRACTIONATION, VOLUME AND TIMING 

R. Dziadziuszko 1 

1 MEDICAL UNIVERSITY OF GDANSK, Dept. of Oncology and Radiotherapy, 

Gdansk, Poland 

Concurrent chemotherapy and thoracic radiotherapy administered early remains 

the best treatment option for patients with limited disease small cell 

lung cancer (LD SCLC). However, sequential treatment with chemotherapy 

and chest irradiation may be considered for patients with significant comorbidities 

and/or if bulky mediastinal disease is present. Several aspects of 

thoracic radiotherapy are still being explored to establish optimal integration 

of chest irradiation in the management of LD SCLC. Radiation dose. 

Conventionally-fractionated thoracic irradiation in the dose range of 45Gy 60 

Gy is typically given concomitantly with chemotherapy in most institutions. 

Maximal tolerated total dose (MTD) of once daily irradiation is around 70Gy in 

this setting. Several reports document better local control for higher radiation 

doses, however survival benefit from thoracic dose escalation is not proven. 

Fractionation. The Intergroup 0096 phase III randomized trial reported by Turrisi 

et al. established survival and local control superiority of twice-daily chest 

radiotherapy to 45 Gy in 30 fractions as compared to 45 Gy of once daily treatment. 

Early grade 3 or higher esophagitis is dose-limiting toxicity and MTD of 

twice-daily fractionation is around 45 Gy. Clinical trials comparing hyperfractionated 

twice-daily radiotherapy to 45 Gy versus once daily or mixed once 

then twice daily radiotherapy schedules to higher doses are currently ongoing. 

Volume. For sequential chemoradiation approach, available evidence 

suggests that limiting chest irradiation portals to post-chemotherapy volume 

does not increase local recurrence rate. However, care should be taken to 

include pre-chemotherapy involved lymph node areas in the treatment volume. 

For concurrent chemo-radiotherapy, limited experience with involvedfield 

chest irradiation suggests acceptable local relapse rates. This approach 

warrants further investigation. Timing. Clinical trials and meta-analyses indicate 

that early thoracic radiotherapy is more effective then late thoracic irradiation 

given concurrently with chemotherapy. It is also established that short 

overall treatment time is associated with improved treatment outcome. The 

risk of severe hematological toxicity from concurrent treatment, particularly 

neutropenia and thrombocytopenia, is markedly increased with large radio-

S 180 DEBATE THURSDAY, SEPTEMBER 18, 2008 

therapy portals and should be individually considered. For some patients, it 

is prudent to defer definitive radiotherapy to increase therapeutic index with 

smaller irradiation volume after 2-3 cycles of chemotherapy. 

550 speaker 

RADIOTHERAPY IN EXTENSIVE DISEASE SCLC 

B. Slotman 1 

1 VU UNIVERSITY MEDICAL CENTER, Radiation Oncology, Amsterdam, 

Netherlands 

Introduction Chemotherapy is the cornerstone of treatment of SCLC and 

recent platinum-based randomized studies in ED-SCLC show a time-to progression 

of less than 6 months and a median survival of less than 1 year. 

Survival of patients with ED-SCLC has shown very little improvement in the 

past few decades and 2-year survival is still below 5%. Many approaches, including 

new agents, combinations of agents and maintenance chemotherapy 

have been evaluated, but they have not shown to be of benefit. Until recently, 

radiotherapy was only used with palliative intent in ED-SCLC patients. In this 

presentation, the role of prophylactic cranial irradiation (PCI) and the possible 

role of chest irradiation in ED-SCLC will be discussed. Prophylactic cranial 

irradiation Brain metastases are common in SCLC and have a great impact 

on the physical and psychological functioning of patients. The response 

of symptomatic brain metastases to systemic or local treatment is poor. This 

has led to the use of PCI in patients with limited disease (LD) who had a complete 

response to initial therapy. PCI was found to reduce the risk of symptomatic 

brain metastases and to improve survival. Within the EORTC Radiation 

Oncology and Lung Cancer Groups, we have performed a randomized 

trial of prophylactic cranial irradiation (PCI) in patients with extensive-disease 

small-cell lung cancer (ED-SCLC) who had had a response to chemotherapy 

(EORTC 22992-08993; Slotman et al., NEJM 357, 664-672, 2007). Patients 

with ED-SCLC (18-75 years; WHO ≤2) and a response to chemotherapy 

were randomized to observation (standard of care) or PCI. The primary 

endpoint was time to symptomatic brain metastases. A CT or MRI scan of 

the brain was performed when one or more key-symptoms suggesting brain 

metastases was present. The study was sized to detect a hazard ratio (HR) 

of 0.44 at 80% power with 2-sided α=0.05. The groups (143 patients in each 

arm) were well balanced for baseline characteristics. PCI decreased the risk 

of developing symptomatic brain metastases (HR 0.27 (95%CI: 0.16-0.44; 

P

POSTERS

Clinical/Disease sites : 

Brachytherapy techniques 

553 poster 

3D ANALYSIS OF A MODIFIED MANCHESTER DOSIMETRY 

SYSTEM TO REDUCE DOSES TO ORGANS AT RISK IN HDR 

INTRACAVITARY BRACHYTHERAPY FOR CERVICAL CANCER 

K. Chalmers 1 , H. Coomber 1 , H. Appleby 1 , P. Humphrey 2 , P. Cornes 3 

1 

BRISTOL HAEMATOLOGY AND ONCOLOGY CENTRE, Radiotherapy Physics 

Unit, Bristol, United Kingdom 

2 

BRISTOL HAEMATOLOGY AND ONCOLOGY CENTRE, Department of 

Radiotherapy, Bristol, United Kingdom 

3 

BRISTOL HAEMATOLOGY AND ONCOLOGY CENTRE, Clinical Oncology, 

Bristol, United Kingdom 

Purpose: The dose delivered in intracavitary HDR brachytherapy treatments 

based on Manchester-type source loading patterns may be compromised because 

of high doses to the rectum and/or bladder. Wong et al a described 

a method (the Hong Kong (HK) method) based on 2D imaging, to lower the 

rectal dose by reducing the relative dwell-time weighting in the ovoid tubes. 

The purpose of this study was to apply the HK method to our standard plans, 

using 3D dosimetry to investigate the effect on D2cc (rectum, bladder) and 

the degree of reduction in cervix dose coverage. 

Materials: The treatment plans of 42 patients with stage T1B-T4a/FIGO1B- 

IVA cervical cancer treated with 3 fractions of brachytherapy with defined- or 

flexible-geometry Fletcher-style applicators (Varian) were studied. D2cc (rectum, 

bladder) and doses to ICRU rectal and bladder points were obtained 

from CT-based 3D dose calculations (Brachyvision, Varian). The calculated 

doses at each fraction had been used to influence the following insertion, and 

to dose-reduce at the final fraction if necessary. Excess of OAR tolerance 

was noted. Where ICRU rectal tolerance had been exceeded, plans were 

recalculated with reduced ovoid dwell times to achieve tolerance. The resulting 

change in the ovoid:IU tube time ratios, the ICRU doses and D2cc, and 

the area enclosed by the prescription isodose at the level of the cervix were 

recorded. 

Results: 19/42 patients had third fraction dose reduction. 14/19 had small 

ovoids. Of 108 fractions included in the study, 38% met the ICRU-based 

rectal dose constraint, whereas 80% met the D2cc dose constraint with the 

standard loading. The corresponding figures for bladder were 64.8% and 

72.6%. To achieve tolerance, the mean ovoid dwell-time weighting relative 

to the IU tube was reduced from 1.41 to (0.68 ± 0.12) in the most extreme 

case. The reduction in treated area at the cervix was between 20-30%, with 

dimensions of long/short axes of the prescription isodose changing from a 

minimum of 5.14/ 4.32 cm, to 4.50/3.78 cm. 

Conclusions: The good correlation (r=0.65) between reducing rectal ICRU 

and D2cc demonstrates that the HK method is an effective method for reducing 

OAR dose. However ICRU rectal point doses were not representative of 

D2cc, and therefore 3D dose calculation eliminates the need for dose reduction 

based on rectal dose in many cases. Cervix coverage by the prescription 

isodose drops to less than a 4 cm diameter and therefore must be assessed 

in individual cases by an oncologist. In Bristol bladder tolerance dose is most 

often the limiting dose, and reducing the ovoid time weighting has less impact 

on reducing bladder dose. Moving from Manchester loading to individual 

plans based on a PTV may be the most consistent way of reducing OAR 

dose. 

a A Pre-optimised Dosimetry System using a Rigid Applicator for Intracavitary 

Treatment of Cervical Carcinoma, Wong VYW et al, Clinical Oncology, 

18:612-620, 2006 

554 poster 

3D BASED BRACHYTHERAPY OF CERVICAL CANCER: EVALUA- 

TION OF GRAPHICALLY ADJUSTED DOSES IN COMPARISON WITH 

STANDARDIZED PLANS. 

E. R. Schellhorn 1 , M. L. M. Laache 1 , K. Reberg 1 , K. Sundfør 2 , H. 

Oksefjell 2 , E. Sundqvist 1 , T. P. Hellebust 3 , E. S. Bergstrand 3 

1 

OSLO UNIVERSITY COLLEGE, Faculty of Health Sciences, Oslo, Norway 

2 

RIKSHOSPITALET/RADIUMHOSPITALET, Dept. of Gynaecological Oncology, 

Oslo, Norway 

3 

RIKSHOSPITALET/RADIUMHOSPITALET, Dept. of Medical Physics, Oslo, 

Norway 

Purpose: In our hospital the intracavitary brachytherapy (ICBT) for cervical 

cancer patients has traditionally been performed with high dose rate (HDR) 

afterloading using a ring/tandem applicator with a standardized source configuration 

forming the classical pear shaped dose distribution. The target dose 

was specified in Point A. In 1997 3D CT based treatment planning was introduced 

in our department, and since 2001 CT-based planning is performed for 

all patients.The treatment plan is now days optimized by graphically adjusting 

the isodoses taking into account diagnostic MR information, findings from 

clinical examinations and doses to organs at risk (OAR). This retrospective 

study aims to compare the optimized dose distribution with the standard plan. 

CLINICAL/DISEASE SITES : BRACHYTHERAPY TECHNIQUES 

S 183 

Materials: This study comprises twenty patients that were treated with HDR 

ICBT using an optimized treatment plan (OptPlan). It is not possible to define 

an accurate target volume using CT [1,2], thus no CTV was delineated. Standard 

plans (StdPlan) were generated for one fraction for each of the twenty 

patients and the minimum dose to the most exposed 2cc volume (D2cc) for 

bladder and rectum were recorded. Doses to point A plus D2cc for rectum 

and bladder were compared for the StdPlan and OptPlan. To evaluate the 

difference between the two plans the 100 % isodose in the StandPlan was 

delineated (V100Std) and the conformity to the 100% isodose in the OptPlan 

was recorded. 

Results: For OptPlans we observed a general average decrease and increase 

in the prescribed standardized dose to point A in 14 and 5 patients, 

respectively. This constitutes an average dose reduction and increase of 16% 

and 17%. 19 patients had a lower dose to D2cc of the bladder and/or the rectum. 

One patient had an increase in dose to both point A and OAR, however 

for the OptPlan D2cc was below the dose constraints defined by our department. 

In average 86% of V100Std was encompassed by the 100% isodose in 

the OptPlan. For 10 patients the volume of the 100% isodose in the OptPlan 

plan was smaller than for the StdPlan. 

Conclusions: Graphically optimized dose plans can be used to lower the 

dose to OARs. This is often not possible without also decreasing the dose to 

point A, as our results show. The point A acts as a surrogate for target dose 

in lack of a CTV outline. In line with the GEC ESTRO recommendations [1,2], 

we plan to start using MR based treatment planning with dose optimization for 

both the outlined target and the OARs in 2008. References:1. Haie-Meder C 

et al 2005 Recommendations from the Gynaecological (GYN) GEC ESTRO 

Working Group (I): Concepts and terms in 3D image based 3D treatment 

planning in cervix cancer brachytherapy with emphasis on MRI assessment 

of GTV and CTV Radiother. Oncol. 74 2352452. Ptter R et al 2006 Recommendations 

from the Gynaecological (GYN) GEC ESTRO Working Group 

(II): Concepts and terms in 3D image-based treatment planning in cervix cancer 

brachytherapy-3D volume parameters and aspects of 3D image-based 

anatomy, radiation physics, radiobiology Radiother. Oncol. 78 6777 

555 poster 

A NOVEL INTRAOCULAR BRACHYTHERAPY DEVICE FOR WET 

AGE-RELATED MACULAR DEGENERATION (AMD) 

B. Guix 1 , B. Woodward 2 , W. Vermeere 2 

1 IMOR FOUNDATION, MEDICAL INSTITUTE FOR RADIOTHERAPY AND 

ONCOLOGY, Radiation Oncology, Barcelona, Spain 

2 NEOVISTA INC, Freemont, CA, USA 

Purpose: A novel intraocular brachytherapy device (NeoVista, Inc.) has been 

developed for the treatment of wet age-related macular degeneration (AMD). 

The handheld device has been designed to allow delivery of ionizing radiation 

focally to the choroidal neovascularization site while minimizing radiation 

exposure to other ocular structures at risk. Information regarding this system 

with respect to its dosimetric characteristics, focused dose distribution 

at target site, therapeutic performance, and dose to critical structures will be 

presented. 

Materials: The brachytherapy system presented is based on a miniaturized 

high-dose rate 90Sr/90Y beta source. Using radiochromic film dosimetry, the 

dose distribution at target site has been characterized with respect to dose 

rate, field size, and field isotropy. Absolute dose rate measurements in terms 

of "absorbed dose to water" are presented based on a specially designed 

reference source calibrated by NIST. During this study, particular attention 

was paid to minimize doses to critical structures of the eye: lens, optic disc, 

and optic nerve 

Results: The radiation field characteristics at target site were found to be 

dependent on a variety of parameters amongst them source activity, sourceto-target 

distance, treatment angle, and particularly the design of the delivery 

device cannula. Given an optimum source-to-target distance of 2.6 mm, the 

50% isodose diameter was determined to be approximately 4.5 mm. The 

absorbed dose rate at treatment site (about 6 Gy/min) is high enough to allow 

for an acceptable irradiation time of typically less than 5 minutes. Doses 

to critical structures are significantly lower than with other radiation oriented 

treatment modalities. Clinical results achieved in feasibility studies are presented 

Conclusions: The main advantage of the NeoVista surgical device is its ability 

to apply a therapeutic radiation dose focally to a limited volume of tissue; 

i.e., the radiation field is localized to the subfoveal neovascularization site. 

The optic disc, optic nerve, and lens receive doses significantly less than 

their known tolerance doses for radiation damage. Clinical results achieved 

to date are equivalent to existing pharmaco-therapeutic therapies for AMD 

with potential benefits to both patients and practitioners. These benefits in 

the areas of long-term efficacy, Quality of Life, and economics are continuing 

to be investigated in additional clinical trials

S 184 CLINICAL/DISEASE SITES : BRACHYTHERAPY TECHNIQUES 

556 poster 

AN ANATOMICAL WAY OF DELINEATING THE PROSTATIC URE- 

THRA IN PROSTATE CANCER BRACHYTHERAPY 

D. Kudrén 1 , T. Lindell 1 , A. M. Neubeck 1 , I. Turesson 1 

1 UPPSALA UNIVERSITY HOSPITAL, Oncology, Uppsala, Sweden 

Purpose: For dose calculations in prostate brachytherapy, the urethra is usually 

delineated with a circular cross-section, often centred on a Foley catheter. 

The urethra, defined in this way, is often seen to move significantly within the 

prostate. Neither this shape nor this mobility seems to be consistent with the 

anatomy of the prostatic urethra. We have therefore sought to visualise the 

prostatic urethra better and hopefully reduce brachytherapy side effects. 

Materials: Since late 2007 this is the standard method used in our hospital for 

visualising the urethra in ultrasonography-guided live-planned high-dose-rate 

prostate brachytherapy:A Foley catheter is inserted into the urinary bladder 

and the catheter balloon is inflated. A Nton catheter is inserted next to the 

Foley catheter, all the way to the bladder neck.Contrast medium is made by 

aerating 510 ml of lidocaine gel by mixing in a syringe. Before gathering the 

first series of transrectal ultrasonograms, the Nton catheter is slowly removed 

while the contrast medium gel is injected through it, thus leaving gel surrounding 

the Foley catheter, which is left indwelling.In the subsequently obtained 

ultrasound images, prior to inserting the applicators, the urethra is delineated 

by the hyper-ecogenic areas caused by the gel. 

Results: Almost always both catheters can easily be inserted. The contrast 

medium is readily seen with the ultrasound. The urethra is delineated with a 

larger and usually more irregular cross-section than that of the Foley catheter 

itself. At this stage the catheter most often is found close to the posterior wall 

of the urethra. The catheter is visible as a zone with less ecogenicity, within 

the gel-filled urethra.The gel can also be perceived in the second series of 

ultrasonograms, after the insertion of the applicators. The position of the 

urethra, as visualised by the gel, does not seem to change much relative to 

the outline of the prostate. The Foley catheter however, does tend to move, 

most often anteriorly. 

Conclusions: This method seems to be an efficient, yet simple way of visualising 

the prostatic urethra during prostate brachytherapy. We believe that this 

method demonstrates the anatomy more accurately than using the catheter 

as the sole reference. We also believe that most of the apparent mobility of 

the urethra within the prostate during treatment is due to movement of the 

Foley catheter inside the urethra and not to displacement of the urethra itself. 

557 poster 

BASE OF TONGUE CANCER TREATED WITH EXTERNAL RADIO- 

THERAPY AND BOOSTED WITH PDR OR HDR BRACHYTHERAPY 

C. E. Mercke 1 , G. Margolin 2 , G. Adell 1 , S. Friesland 1 , G. Wichardt 1 , H. 

Sjodin 1 , G. von Döbeln 1 , J. Nilsson 3 , E. Bengtsson 3 , M. Lundell 3 

1 

KAROLINSKA UNIVERSITY HOSPITAL, Oncology, Stockholm, Sweden 

2 

KAROLINSKA UNIVERSITY HOSPITAL, Department of Head and Neck, 


3 

KAROLINSKA UNIVERSITY HOSPITAL, Medical Physics, Stockholm, Sweden 

Purpose: Base of tongue cancer (BOT) is a common neoplasm of the upper 

autodigestive tract. Therapeutic management classically consists of radiotherapy, 

surgery or a combination of these modalities. Lately neoadjuvant 

and concurrent chemotherapy and inhibition of the EGF receptor during radiotherapy 

have indicated superior results to conventionally fractionated radiotherapy 

alone. Our current institutional policy is to use external radiotherapy 

(ERT) boosted with brachytherapy (BT) for the primary tumour, supplemented 

with induction chemotherapy for fit patients. Surgery is reserved for 

residual neck disease. Preferred BT boost technique is with pulsed dose 

rate (PDR), replaced with high dose rate (HDR) when PDR is not available, 

and aiming at similar BED values for late normal tissue effects. The present 

study reports the pilot results of this policy, evaluating early effect differences 

between boosts given with either PDR or HDR. 

Materials: 50 newly diagnosed pts with squamous cell carcinomas of the 

BOT during 2002-2007 were respectively evaluated. Pts were staged according 

to the 2002 UICC staging system: T1-T2=30 pts, T3-T4=20 pts, stage 

I-II=4 pts, III-IV=46 pts. Male/female ratio was 35/15, median age 63 years 

(range 32-82). Accel. ERT was given to 23 pts (dose range 53.6-68 Gy) and 

conventional fractionation to 27 pts (dose range 50-68 Gy). BT was administrated 

over 2-4 days. PDR was given every second hour 5 times a day and 

HDR with 2 fractions per day, interval 6 hours. BT doses ranged from 9 to 27 

Gy, depending on initial ERT dose. Induction chemotherapy was given to 24 

pts. 

Results: PDR was used for 54% of pts. Median time between ERT and BT 

was 15 days with no difference between boost techniques. At follow-up local 

control was seen in 45/48 pts (2 pts not evaluable because of early death). 

There were 2 failures with PDR and 1 with HDR. 40/50 pts are alive at followup, 

5 dead from BOT cancer (1 regional, 1 distant failure), 3 from lung cancer, 

1 from alcohol abuse and 1 from cardiovascular disease. 

Conclusions: Tumour control was good in a short follow-up period for these 

mostly advanced patients with BOT cancer. No difference was registered 

between the PDR and HDR schedules at least for the dose ranges as used 

in the present study. Radiation dose/time schedules were chosen to reflect 

similar BED values for late normal tissue effects but follow-up time was too 

short to evaluate differences with respect to late complications. 

558 poster 

CLINICAL FEASIBILITY OF MRI BASED DOSE PLANNING IN 

BRACHYTHERAPY FOR CERVICAL CANCER. 

L. Bohr Mordhorst 1 , U. Granlund 2 , B. Bermark 1 

1 

ÖREBRO UNIVERSITY HOSPITAL, Department of Gynaecological Oncology, 

Örebro, Sweden 

2 

ÖREBRO UNIVERSITY HOSPITAL, Department of Medical Physics, Örebro, 

Sweden 

Purpose: MRI has the potential of giving higher accuracy in delineation of 

targets and organs at risk in brachytherapy. The aim of this work was to 

evaluate if MRI based dose planning for brachytherapy in cervical cancer is 

possible in an environment where MRI is not available at the brachytherapy 

department. 

Materials: In a pilot study ten cervix cancer patients were to be treated with 

MRI based dose plans. MRI was performed with a ring applicator in place 

at the first treatment fraction. Immediately after the MRI study a CT scan 

was also performed. For subsequent fractions the aim was to do at least one 

more 3D image (CT or MRI) based dose plan during the rest of the treatment 

course. Patients were treated with either 3 or 5 fractions of 6 Gy. Fractions 

where no 3D imaging was performed were treated according to the dose plan 

from the latest 3D imaging session. At fractions where CT/MRI was done 

patients were implanted and treated under spinal anaesthesia. Implantation 

of the ring applicator was done at the brachytherapy department and patients 

were then transported through culvert to the radiology department for MRI 

examination, then back to the radiotherapy department for CT examination, 

target definition, dose planning and treatment. 

Results: At the time of abstract submission MRI based dose plans have been 

made for 8 patients. These patients have received a total of 31 fractions. At 

9 of these fractions the dose plan was based on MR and CT imaging and 

at 6 fractions the dose plan was based on CT imaging only. The average 

time for the MR imaging based treatment procedure is approximately 5 hours 

from implantation to completed treatment. The procedure seems to be well 

tolerated by patients. 

Conclusions: MRI based treatment planning in brachytherapy is a time consuming 

procedure that requires a high level of cooperation and coordination 

between different specialities, but seems to be clinically realistic even if MRI 

is not available locally at the brachytherapy department.

559 poster 

COMBINED EXTERNAL RADIOTHERAPY AND HIGH DOSE RATE 

BRACHYTHERAPY BOOST OF RELAPSING UROEPITHELIAL 

CANCER IN THE REMAINING URETER 

K. M. Kälkner 1 , E. Bengtsson 2 , A. Valdman 1 , A. Ullén 1 , J. Swärd 3 , M. 

Brehmer 3 

1 KAROLINSKA UNIVERSITY HOSPITAL, Oncology, Stockholm, Sweden 

2 KAROLINSKA UNIVERSITY HOSPITAL, Medical Physics, Stockholm, Sweden 

3 KAROLINSKA UNIVERSITY HOSPITAL, Department of Urology, Stockholm, 

Sweden 

Purpose: To describe a novel organ sparing radiotherapeutic technique in a 

case of tumour relapse in the only remaining ureter. 

Materials: A 73-year-old man with the history a radical cystectomy, rightsided 

nephrectomy, and ureterectomy due to recurrent muscleinvasive uroepithelial 

carcinoma grade II-III, developed in spring 2007 a biopsy-verified relapse 

of low differentiated tumour cells (GIII) in the left proximal ureter. The 

length of the tumour on ureterography was 5 cm. Treatment with endoscopic 

laser was not possible due to the circumferentially growth of the tumour and 

muscleinvasiveness. The patient was offered left-sided nephrectomy and 

ureterecomy, but the operation was refused due to the fact that he would 

be dependent on hemodialysis. Tumour localisation just proximal to the remaining 

kidney excluded the possibility of delivering the high-dose external 

radiotherapy without impairing renal function. A combination of lower dose 

external radiotherapy with a boost of high-dose rate brachytherapy was proposed. 

Results: The patient received a percutaneous nephrostomy catheter draining 

the urine. Beside the nephrostomy catheter, a long thin catheter was placed 

extending through the entire length of tumour and ending at the distal part of 

the ureter. An HDR Iridium-192 source was put through this long catheter using 

afterloading technique with a Nucletron µSelectron machine (Nucletron, 

the Netherlands). The dose was 2.5Gy per fraction at 1cm distance and a 

length at 7cm covering the length of tumour visualised by fluoroscopy plus 

1 cm in cranio-caudal direction. The boost dose of 25Gy was delivered with 

two fractions per day. Brachytherapy was followed by three-dimensional conformal 

radiotherapy with four-field technique. CTV was defined as the tumour 

area plus 2 cm margin. The remaining kidney received less then 75% of total 

external dose.At 6 months follow-up a ureterography was performed with no 

sign of tumour and a ureteroscopy at 9 months did not disclosed any relapse. 

The renal cell function has been stable. No side-effects have been reported. 

Conclusions: Current case report describes the successful attempt to perform 

an organ-sparing treatment of uroepithelial cancer located in the proximal 

ureter. Since the nature of the disease will eventually create a recurrence 

in the uroepithelium of the renal pelvis, the nephrectomy will be inevitable. 

However, for the present patient this treatment created a limitation period 

from hemodialysis. 

560 poster 

DOSE EFFECTS DUE TO DISPLACEMENTS OF TANDEM OVOID 

APPLICATORS DURING PDR BRACHYTHERAPY FOR CERVICAL 

CANCER. 

H. Lotz 1 , M. Moerland 2 , R. Tersteeg 2 , I. Jürgenliemk-Schulz 2 

1 AMSTERDAM MEDICAL CENTRE, Radiotherapy, Amsterdam, Netherlands 

2 UMC, Radiotherapy, Utrecht, Netherlands 

Purpose: To investigate applicator shifts, and the effects on the dose to tumor 

and OAR’s during PDR treatments, which were individually planned according 

to the GEC-ESTRO guideline for 3D gynecologic brachytherapy. 

Materials: Since February 2006, PDR brachy has been applied using MR 

imaging for both delineation of tumor (hr-ctv) and organs at risk (OAR: bladder, 

rectum), and 3D optimization. For 7 patients, receiving 2 PDR treatments 

of 29 or 32 pulses (one pulse per hour, 24 hours scheme), MR imaging with 

the applicator in situ was repeated on the second treatment day. This MR 

was registered to the initial MR scan, and delineation and reconstruction was 

performed again. The average time interval in between the 2 acquisitions was 

21 (SD 6) hours. We evaluated the geometrical shifts of the applicators relative 

to the bony structures, and we calculated the dose parameters (D90% 

(hr-ctv), D2cc (bladder), D2cc (rectum)) for ’day 2’ by applying the same dwell 

positions and dwell times as in the clinically applied plan. All dose values 

were expressed in EQD2 Gy, with α/β=3 for OAR and α/β=10 for hr-ctv. 

Results: In relation to the bony structures, the top of the intrauterine tandem 

shifted on average 4 (SD 9) mm into the ventral direction and 5 (SD 6) mm into 

the cranial direction during the 14 treatments. With respect to the distal part 

of the tandem, the shift was 8 (SD 7) mm ventrally and 2 (SD5) mm cranially. 

For a single PDR treatment, the average D90% (hr-ctv) on ’day 2’ was 1.2 (SD 

2.9) Gy lower than estimated from the treatment plan of day 1, and for the 2 

treatments together it was 2.3 (SD 4.8) Gy lower. The average D2cc (bladder) 

was 2 (SD 5) Gy higher for a single PDR, and 4 (SD 8) Gy higher for 2 PDR’s. 

Similarly, for the rectum the values were 1 (SD 3) Gy higher (single PDR), 

and 2 (SD 4) Gy higher (2 PDRs). One patient showed a large displacement 

of the tandem during both treatments in the same direction. This resulted in a 

total decrease of 10.7 Gy in the D90% (hr-ctv) and an increase of 20.9 Gy in 


S 185 

the D2cc (bladder) and 1.1 Gy in the D2cc (rectum). For all other patients, the 

average decrease in D90% was 1 (SD 3) Gy, and increase in D2cc (bladder) 

and D2cc (rectum) was 1 (SD 4) and 3 (SD 4) Gy, respectively. 

Conclusions: Within a single PDR treatment, applicator shifts occur. In this 

series, the tandem mainly moved ventro-cranially, relative to the bony structures. 

However, despite these shifts, in 6 out of 7 patients, the resulting variations 

in the dose to tumor and OAR’s were acceptable. (For the definitive 

presentation data of more patients will be included in the analysis). 

561 poster 

DOSIMETRIC ANALYSIS FOR FORTY TWO IR-192 HIGH DOSE 

RATE BRACHYTHERAPY SOURCES - TATA MEMORIAL HOSPITAL 

EXPERIENCE OF FOURTEEN YEARS. 

P. Sharma 1 , R. Kinhikar 1 , D. Deshpande 1 , S. K. Shrivastava 2 , K. Dinshaw 

2 

1 TATA MEMORIAL HOSPITAL, Medical Physics, Mumbai, India 

2 TATA MEMORIAL HOSPITAL, Radiation Oncology, Mumbai, India 

Purpose: High dose rate brachytherapy (HDRBT) has been widely used in 

Tata Memorial Hospital since 1994. The dosimetry for Ir-192 source is critical 

and needs extensive quality assurance. To analyze the results of dosimetry 

performed since last 14 years to measure the source strength for HDRBT Ir- 

192 source at our hospital. The dosimetric analysis of 42 sources has been 

reported. 

Materials: An eighteen channel Microselectron HDRBT machine (Nucletron 

BV, Netherlands) was installed and commissioned in 1994 at Tata Memorial 

Hospital. The machine has the capability to accommodate a single 12 Ci 

Ir-192 source in a tungsten container. Till date, dosimetry was carried our 

for 42 sources. The activity measurements were carried out with Well Type 

Chamber (400 CC, 4Π geometry) and Source Dosimetry System (SDS). The 

Reference Air Kerma Rate (RAKR) measurements were carried out with a 

0.6 CC cylindrical ion chamber (PTW, Germany) and UNIDOS electrometer. 

The RAKR measurements were performed at 10 cm distance from the 

source in an indigenously designed jig. The peak response of the source per 

dwell position was estimated and the final measurements were carried out 

at the position of peak response. The measured source strength was then 

compared with the source strength quoted by the manufacturer in the source 

calibration certificate. 

Results: The mean variation between the measured (Well Type Ion chamber) 

and the quoted source strength was found to be 0.21 % (SD 1.75). Similarly, 

the mean variation between the measured (RAKR) and the quoted source 

strength was 0.87% (SD 1.87). Both the dosimetry measurements revealed 

the mean variation of < 1% from the quoted source strength. 

Conclusions: The dosimetry performed for 42 sources was well within the 

acceptable limits and the measured source strength was always used for clinical 

treatment planning of HDRBT treatments. The functionality of HDR machine 

was found satisfactory for last 14 years and thus safely being used for 

clinical applications at our hospital. 

562 poster 

ESTIMATION OF USEFULNESS OF THE NEW BRONCHOSCOPIC 

DEVICES FOR TARGET DEFINITION IN ENDOBRONCHIAL HDR 

BRACHYTHERAPY. 

A. Kasprowicz 1 , A. Kulik 1 , J. Lyczek 1 , M. Dabkowski 1 

1 MARIA SKLODOWSKA CURIE MEMORIAL CANCER CENTER, Brachytherapy 

Department, Warsaw, Poland 

Purpose: Endoscopic imaging techniques develop very dynamic nowadays. 

Some of them, particularly special light bronchoscopy as AFI or NBI, allow to 

detect pathological lesions in bronchial mucosa and estimate its spread. The 

aim of the study is estimation of usefulness of the new bronchoscopic devices 

for target definition in endobronchial HDR brachytherapy. 

Materials: From October 2007 to March 2008 twelve patients (9 men, 3 

women), aged 45 73 years were enrolled into the study. All of them had 

centrally located, endobronchial, histopatologically proven non small cell lung 

cancer. 

Results: All patients participated in the study underwent bronchofiberoscopy 

with conventional white light imaging as a first step of examination. The length 

of infiltration, its proximal and distal margin were estimated. Then special 

light bronchoscopy was performed using two types of bronchofiberoscopes 

: EVIS - LUCERA type F260 with AFI system exploited natural fluorescence 

of bronchial epithelium and EVIS - EXERA2 type 1T180 with NBI system 

visualized subepithelial vascular patterns. Any changes in bronchial mucosa 

near the main tumor were sampled. Endobronchial HDR brachytherapy was 

performed after histopathological results were known. There was necessity 

to elongate of irradiated section about 9 -20 % in 7/12 cases because of 

histopatological findings. 

Conclusions: Short time and small investigated group do not unambiguously 

allow to estimate the value of presented method. But first results are promising 

and study will be continued.


563 poster 

GROWTH RETARDATION AND SURVIVAL PROLONGATION OF 

EXPERIMENTAL LUNG CARCINOMA BY INTERSTITIAL 224RA- 

LOADED WIRES RELEASING DIFFUSING ALPHA-EMITTING 

ATOMS 

Y. Keisari 1 , T. Cooks 1 , M. Efrati 1 , H. Bittan 2 , M. Schmidt 2 , L. Arazi 2 , I. 

Kelson 2 

1 

TEL-AVIV UNIVERSITY / FACULTY OF MEDICINE, Department of Human 

Microbiology, Tel-Aviv, Israel 

2 

TEL-AVIV UNIVERSITY /SCHOOL OF PHYSICS & ASTRONOMY, Department 

of Nuclear Physics, Tel-Aviv, Israel 

Purpose: Alpha particles are substantially more effective in cell killing than 

photons and electrons. However, the short range of alpha particles in tissue 

has so far precluded their use against solid tumors. We have developed a 

new form of brachytherapy that enables the treatment of solid tumors with alpha 

radiation, which was termed- Diffusing Alpha-emitters Radiation Therapy 

(DART). The basic idea of DART is to insert into the tumor sources loaded 

with 224Ra atoms, which release from their surface short-lived alpha-emitting 

atoms. These disperse inside the tumor and deliver a lethal dose through their 

alpha decays. The present study examines the anti-tumoral effects resulting 

from the release of alpha emitting radioisotopes into solid lung carcinoma 

(LL/2 and A427) tumors. We assessed the efficacy of the short-lived daughters 

of 224Ra, which are released into the malignant tissue, to produce tumor 

growth retardation and prolong life. 

Materials: Radioactive wires (0.3 mm diameter and 5 mm long) with 224Ra 

activities in the range 12-33 kBq were inserted into LL/2 tumors in C57BL/6 

mice and into human derived A427 tumors in athymic mice. Tumor development 

was recorded during 21 days (LL2) or 28 days (A427) and survival was 

monitored for 45 days (LL2) or 120 days (A427). An in-vitro set-up tested the 

dose dependent killing of tumors cells exposed to alpha particles. 

Results: The insertion of a single DART wire into the center of 6-7 mm (130 

mm average volume) tumors had a pronounced retardation effect on tumor 

growth in the murine model, leading to a significant inhibition of 49% (LL2) 

and 93% (A427) in tumor development, and prolongations of 48% (LL2) in 

life expectancy. These observed effects were strengthened when tumors 

were treated with two DART wires. In the human model more than 80% 

of the treated tumors disappeared or shrunk. Autoradiographic analysis of 

the treated sectioned tissue revealed intratumoral distribution of radioactive 

atoms around the wires, and histological analysis revealed corresponding areas 

of necrosis. In-vitro experiments demonstrated a dose-dependent killing 

of tumors cells exposed to alpha particles. 

Conclusions: The results indicate that DART causes significant damage 

to lung carcinoma, and prolongs survival. DART treatment holds great potential 

for the treatment of human lung cancer, and might be augmented by 

chemotherapy and other modalities like immunotherapy or anti growth factors. 

564 poster 

HIGH DOSE RATE AFTERLOADING INTRALUMINAL BRACHYTHER- 

APY FOR ADVANCED INOPERABLE ANO-RECTAL CARCINOMA 

P. Hoskin 1 , C. Corner 1 , L. Bryant 1 , C. Chapman 1 , R. Glynne-Jones 1 

1 MOUNT VERNON CANCER CENTRE, Mount Vernon Hospital, Northwood, 


Purpose: This is a retrospective review of 79 consecutive patients treated 

between 2001 and 2007 with locally advanced ano-rectal cancer. 

Materials: 52 patients were unfit for major surgery but received radiotherapy 

with radical intent, either as a 12Gy at 1cm boost after external beam radiation 

45Gy in 25 fractions or as monotherapy treating up to 36Gy at 1cm in 

6Gy fractions, 2 to 3 times weekly. 27 patients with advanced or metastatic 

disease received palliative treatment predominantly a single fraction of 10Gy 

at 1cm. The tumour was located in the anal canal in 15 patients and the 

remainder had rectal tumours. The median age was 82 years (range 33-97 

years) 

Results: Objective local tumour response was seen in 41 of 48 assessable 

patients (85%) of whom 28 had a complete response (58%) and 13 had a 

partial response with > 50% regression (27%). The most common symptom 

was rectal bleeding affecting 52 patients. This responded to treatment with 

a complete response rate of 63% and partial response rate of 43%. Mucous 

discharge affected 23 patients of whom 35% had a complete response and 

43% a partial response. Rectal pain was present in 18 patients with a 50% 

compete response and 33% partial response and diarrhoea was present in 

21 patients with a 43% complete response and 43% partial response. Median 

duration of symptom responses was 3 months (range 1 73 months). Median 

survival for patients treated with radical intent was 18.5 months (range 2-119 

months), and 6 months (range 1week-37 months) for the palliative patients. 

Six patients reported late toxicity all of whom had received treatment with 

radical intent with 3 cases of radionecrotic ulcer, 2 strictures and 1 fistula. 

Conclusions: In conclusion intraluminal HDR brachytherapy is effective as 

local treatment both in the radical and palliative setting, with a high tumour 

and symptom response rates and acceptable late toxicity. 

565 poster 

HIGH DOSE RATE BRACHYTHERAPY IN SKIN CANCERS: PATIENT 

CONVENIENCE, LOCAL CONTROL AND COSMETIC RESULTS 

S. Rodriguez Villalba 1 , M. Santos 1 , J. Richart 1 , N. Louis-Belle 1 , J. 

Perez-Calatayud 2 , F. Ballester 3 , D. Granero 2 , M. C. Pujades 2 

1 

CLINICA BENIDORM HOSPITAL, Radiotherapy Department, Benidorm, 

Spain 

2 


3 

UNIVERSITY OF VALENCIA-IFIC, Atomic, Molecular, and Nuclear Physics, 


Purpose: Primary non melanoma skin cancers are usually treated with 

surgery or radiotherapy. However, excellent local tumour rates and cosmetic 

outcomes with low toxicity are obtained with high dose rate brachytherapy 

(HDRB) using interstitial implants or superficial moulds. 

Materials: From 1998 to 2007, 49 primary skin lesions on 42 patients were 

treated with HDRB. 23 were squamous cell carcinomas, 22 basal cell carcinomas, 

3 Bowel disease and 1 Merkel tumour. The disease was macroscopic 

in 39 cases and in 10 patients the treatment was made after resection with 

affected microscopic margins. 6 patients had received external radiotherapy 

several years ago and in one patient with an enormous Bowen’s disease 

HDRB was used as boost after external radiotherapy. 32 lesions were treated 

using an interstitial flexible catheters technique and 17 with a thermoplastic 

mould placing the flexible catheters in the surface. In both cases the catheters 

were separated 1 centimetre. Usually we used interstitial implants for macroscopic 

lesions and surface mould for microscopic disease or lesions less than 

1 cm of diameter. The dose was calculated between 0,5 and 1 cm. The median 

dose was 3200 cGy (1800 cGy 4500 cGy) with a median of 10 fractions 

(4 10). Patients with microscopic disease have received 9-10 fractions of 

300 cGy, twice a day, with an interval of 4 6 hours. The other patient was 

diagnosed of a Bowen’s disease and received 6 fractions of 600 cGy, one 

treatment a day. The fraction in the patients with macroscopic disease varies 

depending of the size and location of the lesion. Most of the patients were 

treated with 8 fractions of 450 cGy, twice a day, 10 x 400 cGy or 10 x 450 cGy 

in big lesions. 

Results: The local control of all patients was 96 %. They were two patients 

treated in the first 2 years with a surface mould failed locally, 10 and 

11 months after the HDRB treatment respectively. Both of them were rescue, 

the first with a laser resection and the second one with an interstitial implant. 

After these failures we began to do to all patients an ultrasound of the tumour 

or of the surgical bed in the cases of microscopic disease before the 

treatment. We usually choose the interstitial technique when the ultrasound 

shows more than 5 mm of deep in the lesion. After this policy, we have not 

had more local failures. Acute and chronic side effects were scored according 

to RTOG scoring system. Twelve patients developed grade 1 acute skin toxicity 

(24.4 %), 25 grade 2 (51 %). None patient developed grade 3-4 acute skin 

reactions. The acute side effects were maximal 10 days after the treatment 

and subsided a median of time of 12 days (6 25 days). 

Conclusions: HDRB with an ultrasound for optimize dosimetry is a useful 

and comfortable technique in the treatment of primary skin cancers, with low 

toxicity and excellent cosmetic results. Local control is similar to other standard 

approaches like surgery of external beam radiotherapy. 

566 poster 

HIGH DOSE-RATE INTRACAVITARY BRACHYTHERAPY IN ELDERLY 

WOMEN WITH CERVICAL CANCER 

M. Melo 1 , P. Novaes 1 , H. Balloni 1 , G. Teixeira 1 , D. Castro 1 , J. V. Salvajoli 

1 

1 HOSPITAL A. C. CAMARGO, Radiotherapy, Sao Paulo, Brazil 

Purpose: To investigate the technical aspects and safety of high dose rate 

intracavitary brachytherapy applications in elderly women with cervical cancer. 

Materials: From May 2000 through June 2006, 544 intracavitary brachytherapy 

applications were performed for women with advanced (IIIB) cervical carcinoma. 

344 procedures were done in patients with less than 70 years old 

(median 49) and an other 200 were done in patients with more than 70 years 

old (median 76). Itch patients perform a mean of 3.8 insertions (median 4) all 

with high dose-rate afterloading and Fletcher applicators. All patients were 

also submitted to a four-field technique (box) external beam radiotherapy with 

a median of 54gy. Use of general anesthesia was not routinely performed for 

all the application. 

Results: The older women group and the younger ones were found homogeneous 

in some characteristics: teletherapy and brachytherapy doses (51 vs. 

52GY and 26 vs. 27GY respectively), hysterometry (57 vs. 58mm) and involvement 

of lower vagina (11 vs. 10%). In others, there was an expected difference 

between the groups with the older women receiving less chemotherapy 

(12 vs. 29%; p = 0.03) and shorter total treatment time (59 vs. 62 days; 

p = 0.01). Some little differences were find in technical aspects with older 

women using smaller vaginal Fletcher ovoids (36% mini, 46% small vs. 18% 

mini, 58% small; p = 0.01), less vaginal packing (64 vs. 76%; p = 0.002) 

and greater doses on rectum (75x70%, p = 0.0001) and bladder (66x60%;

p = 0.0001) ICRU points. Our major results showed that there was no problem 

with safety in relation to intracavitary application for elderly women, with 

the older patients needing similar proportion of anesthesia (22 vs. 25%; p = 

0.4) and post-insertion analgesic medication (22 vs. 29%; p = 0.08) than the 

younger ones. older women also had similar incidence of treatment interruptions 

or abortions (12 vs. 14%; p =0.6). 

Conclusions: high dose rate intracavitary brachytherapy is a safety and technically 

viable procedure for elderly women with cervical cancer. 

567 poster 

HIGH-DOSE-RATE (HDR) BRACHYTHERAPY OF PATIENTS WITH 

BASAL CELL SKIN CARCINOMAS OF THE FACE WHO PREVIOUSLY 

UNDERGONE SURGERY: RESULTS OF MARIA SKLODOWSKA- 

CURIE MEMORIAL CANCER CENTER AND INSTITUTE OF 

ONCOLOGY (GLIWICE, POLAND). 

B. Smolska 1 , I. Wzietek 2 , B. Bialas 3 , M. Szlag 4 , K. Trela 2 , M. Giglok 1 , 

A. Namysl-Kaletka 2 , A. Zajusz 1 

1 MARIA SKLODOWSKA-CURIE MEMORIAL CANCER CENTER AND INSTITUTE 

OF ONCOLOGY, II Radiotherapy Clinic, Gliwice, Poland 


OF ONCOLOGY, Radiotherapy , Gliwice, Poland 


OF ONCOLOGY, Brachytherapy, Gliwice, Poland 


OF ONCOLOGY, Radiotherapy and Brachytherapy Planning, Gliwice, Poland 

Purpose: To evaluate the efficacy, toxicity and cosmetic results after highdose-rate 

(HDR) brachytherapy for patients with basal cell skin carcinomas of 

the face who previously undergone surgery. 

Materials: From July 2001 to December 2005, 113 lesions of basal cell carcinomas 

of the face were treated in Maria Sklodowska-Curie Memorial Cancer 

Center and Institute of Oncology (Gliwice, Poland) by HDR brachytherapy 

with iridium-192. The analysis included 21 patients who were treated 

with adjuvant HDR brachytherapy after surgery (first excision in 11 cases and 

secondary excision in 10 cases). Postoperative HDR brachytherapy was indicated 

in 17 cases because of incomplete excision and in 4 cases because 

of uncertain margins. The tumors were localized in the nose 7 lesions, in the 

periorbital region -7, in the periauricular region -3, in the forehead -2, others 

-2. The median age was 63 years (range 43-79) with sex ratio F/M=2.5. Patients 

were treated as follows: 12 - 3 times per week, 7 - 2 times per week, 2 

- every day. The median of total dose administrated was 36 Gy (range 24-45 

Gy) with a median of 8 fractions (range 5-9). The median overall treatment 

time was 18 days (range 12-26). Localization of the scar in 19 cases required 

individual custom surface mold applicators, built over a plaster mold of the 

patient’s face to obtain in the whole area of the applicator a uniform dose 

distribution in the surface of the applicator and at 5 mm depth from the skin 

surface. Only in 3 patients standard HAM applicators could be implemented. 

The reference point was from 0.3 to 0.5 cm from the applicator surface. Median 

number of catheters used was 2 (range 1-3). Toxicity was assessed 

according to RTOG/EORTC scoring system. 

Results: The median follow-up was 27 months (1-70 months). Three year 

recurrence-free survival rate for all patients was 87 %. There were 4 local recurrences. 

In all cases secondary excision were performed. The median time 

to recurrence was 29 months (range 13-43). No patient required the treatment 

interruption and all finished the treatment on the planned total dose. In 

general acute toxicity was acceptable; however grade 4 toxicity (skin necrosis) 

occurred in 1 patient six weeks after the treatment. Grade 1 late reactions 

had developed in 52% of patients, consistent with some pigmentation 

changes and slight atrophy. All patients assessed very good cosmetic results 

of treatment after recovery of acute skin reactions. 

Conclusions: Modern brachytherapy techniques allow individualizing the 

treatment and obtain uniformed dose distribution what ensure low toxicity and 

gives excellent cosmetic results. This is the reason why the use of postoperative 

HDR brachytherapy is worth to be considered in a case of incomplete 

excision of the tumor localized in the area where safety surgical margins are 

difficult to be obtained. 

568 poster 

HIGH-DOSE-RATE (HDR) BRACHYTHERAPY OF PATIENTS WITH 

PRIMARY AND RECURRENT BASAL CELL SKIN CARCINOMAS OF 

THE FACE: RESULTS OF MARIA SKLODOWSKA-CURIE MEMORIAL 

CANCER CENTER AND INSTITUTE OF ONCOLOGY (GLIWICE, 


S 187 

POLAND) 

I. Wzietek 1 , B. Smolska-Ciszewska 2 , B. Bialas 3 , M. Szlag 4 , K. Trela 1 , M. 

Giglok 2 , A. Namysl-Kaletka 1 , A. Zajusz 2 


OF ONCOLOGY, Radiotherapy, Gliwice, Poland 


OF ONCOLOGY, II Radiotherapy Clinic, Gliwice, Poland 


OF ONCOLOGY, Brachytherapy , Gliwice, Poland 


OF ONCOLOGY, Radiotherapy and Brachytherapy Planning, Gliwice, Poland 

Purpose: To evaluate the effectiveness and normal tissue reactions after 

high-dose-rate brachytherapy of patients with basal cell skin carcinoma of the 

face. 

Materials: From July 2001 to December 2005, 113 lesions of basal cell carcinomas 

of the face were treated in Maria Sklodowska-Curie Memorial Cancer 

Center and Institute of Oncology (Gliwice, Poland) by HDR brachytherapy 

with iridium-192. The analysis included 63 patients with primary cancer and 

29 with recurrent tumor. Standard HAM applicators were implemented in 28 

(30%) patients and 64 (70%) patients were treated with custom surface mold 

applicators, built over a plaster mold of the patient’s face. The stage distribution 

was: T152%, T2-32%, T33%, T4-9% and TX-4% respectively. The 

tumors were localized in the nose 41% lesions, in the periauricular region 

-22%, in the periorbital region -13%, in the forehead -8%, others -16%. The 

median age was 72 years (range 35-101) with 51% male and 49% female. 

Patients were treated as follows: 61% - 3 times per week, 32% - 2 times per 

week, 2% - every day, 5% - twice a day (with an inter-fraction interval of 6 

hours). The median of total dose administrated was 40 Gy (range 20-64 Gy) 

with a median of 8 fractions (range 4-15). The median overall treatment time 

was 20 days (range 7-38). The reference point was from 0.4 to 1.0 cm from 

the applicator surface (median 0.5). Median number of catheters used was 

3 (range 1-10). Toxicity was assessed according to RTOG/EORTC scoring 

system 

Results: The median follow-up was 22 months (1-64 months). The evaluation 

of local response one month after the treatment was: 79 (86%) complete 

and 13 (14%) partial regression. There were 8 local recurrences, 5/63 patients 

treated for primary tumor and 3/29 patients treated for recurrent tumor. 

The median time to recurrence was 20.4 months (range 6.6-39.5). For patients 

treated with radical intent five year recurrence-free survival rate was 

81% in group with primary cancer and 66% in group with recurrent tumor 

(p=0.5). Local progression occurred in 7 lesions: 3/63 patients treated for primary 

lesion and 4/29 patients treated for recurrent tumor. The median time 

to progression was 12.7 months (range 4.9 19.3). All patients presented a 

certain degree of skin erythema at treatment completion. Acute toxicity was 

responsible for treatment interruption in 2 cases and finishing the treatment 

one fraction earlier in 2 cases. Grade 1 late reactions had developed in 58% 

cases, consistent with some pigmentation changes and slight atrophy and 

only one (1%) grade 2 consistent with patchy atrophy and moderate teleangiectasia. 

Cosmetic effect of treatment assessed by patients after recovery of 

acute skin reactions was very good in 85%, good in 9%, satisfactory 5% and 

poor in 1% of all cases. 

Conclusions: HDR brachytherapy is safe and effective for the treatment of 

basal cell skin carcinomas of the face with low toxicity and very good cosmetic 

results. 

569 poster 

IMPORTANCE OF NEEDLE POSITIONS IN INTERSTITIAL HIGH- 

DOSE-RATE PROSTATE IMPLANTS WITH REGARD TO DOSIMET- 

RIC PARAMETERS 

G. Fröhlich 1 , T. Major 2 , P. Ágoston 3 , J. Fodor 2 

1 

SEMMELWEIS UNIVERSITY, School of PhD Studies, Budapest, Hungary 

2 

NATIONAL INSTITUTE OF ONCOLOGY, Department of Radiotherapy, 

Budapest, Hungary 

3 

NATIONAL INSTITUTE OF ONCOLOGY, Budapest, Hungary 

Purpose: To evaluate the effect of the catheter positions and optimization 

methods on the dosimetric quality of transrectal ultrasound guided high-doserate 

prostate implants. 

Materials: Treatment plans of 25 prostate implants with real needle positions 

(RNP) were evaluated using dose-volume histograms. Then, in a new plan 

the needles were distributed uniformly (UNP) and only geometrical optimisation 

(GO) was applied. Next, graphical optimisation (GRO) was also performed. 

Student t-test was used to compare dose-volume parameters: the 

fraction of the prostate volume receiving 90 (V90), 100 (V100), 150 (V150) 

and 200% (V200) of the prescribed dose, dose delivered to 90% of the 

prostate volume (D90), minimum dose in the prostate (Dmin), maximal dose 

to rectum (Dr) and urethra (Du) reference points, dose to the most exposed 

volume of 2 cm 3 (D2) of the rectum and 0.1 cm 3 (D0.1) and 1% of the urethra 

(D1). Dose non-uniformity ratio (DNR) and dose homogeneity index (DHI) 

were calculated to quantify dose homogeneity. The dose conformity was assessed 

with the use of conformal index (COIN). 

Results: Using uniform needle distributions and GO the V90, V100, V150,


V200, D90 and Dmin decreased significantly (99.4 vs. 95.3; 96.5 vs. 89.3; 

33.2 vs. 24.2; 11.0 vs. 7.6; 109.1 vs. 99.9 and 89.8 vs. 75.1%, respectively) 

compared to plans with RNP. Du, D1 and D0.1 also decreased (115.2 vs. 

110.1; 130.6 vs. 121.7; 121 vs. 115%). Dose homogeneity was better (DNR: 

0.32 vs. 0.26) but the coverage was less (V100: 97 vs. 89%).With GRO 

the V90, V100, V150, V200, D90 and Dmin increased significantly (95.3 vs. 

99.6; 89.3 vs. 96.9; 24.2 vs. 26.7; 7.6 vs. 8.8; 99.9 vs. 109.8 and 75.1 vs. 

91%). The mean maximal dose to rectum decreased (Dr: 79.1 vs. 72.9%) 

but to urethra it increased (Du: 110.1 vs. 115.3; D1: 121.7 vs. 131.5; D0.1: 

115 vs. 121.3%). The coverage and conformality also improved (V100: 89 

vs. 98%; COIN: 0.65 vs. 0.69).Comparing the plans with RNP and UNP with 

GO+GRO the high dose regions and maximum rectum dose were significantly 

lower (V150: 33.2 vs. 26.7; V200: 11.0 vs. 8.8; Dr: 76.6 vs. 72.9%) and the 

consequence is the better DNR parameter (0.32 vs. 0.27). The V100 did not 

change, the COIN was better but not significantly (0.67 vs. 0.69). 

Conclusions: Using uniform needle placements and GO does not result acceptable 

dose distribution, except for the dose homogeneity. With GRO the 

quality of the implants can be significantly improved. The advantages of uniform 

needle positions are the more uniform dose distribution in the prostate 

and lower dose to rectum. 

570 poster 

INTERSTITIAL BRACHYTHERAPY FOR DOSE ESCALATION IN 

HEAD AND NECK CANCER: A VIEW FROM THE DEVELOPING 

WORLD 

J. Goswami 1 , S. Mitra 1 , S. Saha 1 , N. Patra 1 , A. Ghosh Dastidar 1 , S. 

Basu 1 , K. Chatterjee 1 , S. Sarkar 1 , J. Jayanti 1 , K. Ghosh 1 

1 MEDICAL COLLEGE HOSPITAL, Radiotherapy, Kolkata, India 

Purpose: Brachytherapy in head and neck cancer allows dose escalation 

with tolerable toxicities in head and neck cancer. This study is to assess 

efficacy and toxicity associated with external beam radiation therapy (EBRT) 

and high dose rate [HDR] interstitial 192Ir brachytherapy for the treatment of 

squamous carcinoma of the oropharynx and oral cavity. 

Materials: Between November 2004 and June 2007, 33 patients with 

oropharynx and oral cavity carcinomas were treated with 192Ir interstitial implants 

after EBRT at Medical College Hospital, Kolkata. Fifteen patients had 

early stage disease (Stage I and II), and 18 had advanced stage disease 

(Stage III and IV). Eleven patients had cervical lymph node involvement at 

diagnosis. All received EBRT to a median dose of 50 Gy (range 4666 Gy) to 

the primary tumor and regional lymph nodes before brachytherapy. Interstitial 

implant was performed within 1-2 weeks after EBRT. Seven patients with 

advanced stage disease underwent concomitant chemotherapy with EBRT. 

Node-positive patients with residual neck disease also underwent neck dissection. 

Brachytherapy dose[HDR] in combination with EBRT varied from14 

to 21 Gy, 3Gy per fraction, two fractions daily with a minimum gap of 5-6 

hours . Local control, freedom from disease, progression free survival and 

complications were assessed. 

Results: Follow up duration was between 3 months and 30 months. At the 

end of treatment with radiation 79% achieved complete response (CR) [15/15 

in Early stage vs. 11/18 in the advanced stage (p

Results: Procedure time and tolerability, as assessed by VAS, were 61 (55- 

70) minutes, and 1 (0-3), respectively. No complications were observed. All 

of 13 inserted needles were inside HR-CTV and outside OAR. Differences in 

pre-planned and actual needle depths and needle insertion points were 0.5 

(st. dev 0.35) cm and 3 (st. dev. 4.6) degrees, respectively. Differences in 

preplanned and actual D90 and V100 for the HR-CTV were 3.7 (st. dev. 2.2) 

Gy and 3.8 (st. dev. 3.8) %, respectively. Doses to OAR were comparable. 

The ratio between D90 for the HR-CTV and D2cc for the most exposed OAR 

was 1.3 for standard intracavitary plan and 1.7 for pre-plan based approach. 

Conclusions: The procedure was well tolerated and feasible. Pre-plan geometry 

could be reproduced thoroughly at BT application. Pre-planning approach 

could serve as a basis for accomplishment of BT in a single, optimized 

insertion. Based on these results, a prospective study of MRI assisted BT 

pre-planning in patients with insufficient response and/or unfavourable topography 

after external beam radiotherapy, is being initiated at our institution. 

573 poster 

PREOPERATIVE HDR BRACHYTHERAPY IN IB AND IIA CERVICAL 

CANCER PATIENTS - TOLERANCE AND EFFICACY 

S. Kellas 1 , B. Bialas 1 , M. Fijalkowski 1 , J. Bystrzycka 1 , K. Raczek- 

Zwierzycka 2 

1 MARIA SKLODOWSKA CURIE MEMORIAL CANCER CENTRE AND INSTITUTE 

OF ONCOLOGY, G, Department of Brachytherapy, Gliwice, Poland 

2 MARIA SKLODOWSKA CURIE MEMORIAL CANCER CENTRE AND INSTITUTE 

OF ONCOLOGY, G, Gliwice, Poland 

Purpose: The aim of the study was to analyse the efficacy and tolerance of 

preoperative HDR brachytherapy in patients with cervical cancer IB and IIA. 

Materials: From January 1996 to December 2002 in Maria Skodowska-Curie 

Memorial Cancer Centre and Institute of Oncology, Gliwice Branch 108 patients 

with cervical cancer stage IB-IIA were treated with preoperative HDR 

brachytherapy (BT) (IB40,7%; IIA59,3%). The most frequent was squamous 

cell carcinoma. In preoperative BT total dose to point A ranged from 30 to 45 

Gy in 6-9 fractions twice a week. The fraction dose was 4-5 Gy at point A. Six 

weeks after BT all patients underwent radical Wertheim-Meigs hysterectomy. 

Patients with disadvantageous risk factors or with positive specimen histology 

had a complementary therapy: external-beam radiotherapy (EBRT) either 

Co60 or 6MV photons given to the whole pelvic volume in daily fractions of 

2 Gy up to total dose of 36-52 Gy (17 patients) or EBRT with cisplatin-based 

chemotherapy given weekly at the dose of 30-40 mg/m2 in 5-7 fractions (7 

patients) or chemotherapy (3 patients). Acute and late radiation toxicity were 

evaluated according to EORTC/RTCG. 

Results: In postoperative specimen histopathology 87 patients (80,6 %) had 

tumor-free specimen in BT target (in cervix and cavity). In this group there 

were 14 cases of cancer cells outside the BT target. In 21 patients (19,4%) 

cancer cells were still in BT target and in this group there were 11 patients 

who had also cancer cells outside the target. In patients with complementary 

therapy 5 year disease-free survival rate was 77,8%, recurrence rate was 

18,5% and the lack of remission - 3,7%. In 81 patients without complementary 

therapy 5 year disease-free survival rate was 90,1%, recurrence - 8,7% and 

the lack of remission - 1,2%. 5,5% of patients developed acute toxicity in 

both rectum and bladder only in I and II grade EORTC/RTCG. Late severe 

complication occurred only in rectum in 1,8%. 

Conclusions: Preoperative HDR brachytherapy in patients with IB and IIA 

cervical cancer is an effective and well tolerated therapy with acceptable rate 

of side effects. 

574 poster 

RADIOTHERAPY OF SOLID MALIGNANT HUMAN TUMORS IN 

ATHYMIC MICE BY INTRATUMORAL 224RA-LOADED WIRES 

RELEASING ALPHA EMITTING ATOMS CAN ACHIEVE LOCAL 

TUMOR CONTROL. 

I. Kelson 1 , T. Cooks 1 , M. Tal 1 , R. Etzyoni 1 , M. Schmidt 2 , L. Arazi 2 , Y. 

Keisari 1 

1 

TEL-AVIV UNIVERSITY / FACULTY OF MEDICINE, Department of Human 

Microbiology, Tel-Aviv, Israel 

2 

TEL-AVIV UNIVERSITY / SCHOOL OF PHYSICS & ASTRONOMY, Department 

of Nuclear Physics, Tel-Aviv, Israel 

Purpose: Alpha radiation (high LET of 100-200 keV/micron) is the most lethal 

form of radiation. Yet, its short range in tissue (


576 poster 

SIMPLIFIED BRACHYTHERAPY DOSIMETRY SYSTEMS FOR 

MEDICALLY INOPERABLE EARLY STAGE ENDOMETRIAL CANCER 

USING THE VARIAN TM ENDOMETRIUM APPLICATOR 

C. French 1 , A. Atkin 1 , P. Cornes 1 

1 BRISTOL HAEMATOLOGY & ONCOLOGY CENTRE, Bristol, United Kingdom 

Purpose: The increasing incidence of endometrial cancer and its association 

with diabetes, obesity, hypertension and heart failure means radiotherapy is 

used increasingly as a sole treatment modality inpatients unfit for surgery. 

Manchester/Fletcher cervix applicators are used frequently but with only a 

single intrauterine tube deliver inhomogeneous dose to the uterus. Heyman 

packing with Norman-Simon applicators require complex dosimetry and are 

not reproducible on multiple fractions. Madison type 2-channel applicators offer 

improved dose distribution but require complex dosimetry for 2-D planning 

to customised dose points (M and W). 

Materials: Insertions in actual patients are compared using both 

Manchester/Fletcher cervix and Varian TM Endometrium 2 channel (Madison 

type) intrauterine applicators in 3-D using an image-guided Varian 

Brachyvision TM system. We replace the complex Madison uterine 2Ddosimetry 

system with the GEC/ESTRO cervix 3D-system, reporting doses 

at the ICRU-38 reference point-A and conform that reference isodose to the 

CTV (the uterus). This dose is delivered by passing an HDR source up each 

arm of the ’Y’ shape to the prescribed positions. 

Results: For a typical 5.4Gy Iridium-HDR fraction, the DVH data shows the 

Varian TM Endometrium intrauterine applicator offers superior coverage of CTV 

to Manchester/Fletcher, with D80 of 80.5% and 62.1% respectively. The 

equivalent doses to OAR are significantly reduced, with LQED 2Gy/# D2cc 

of bladder of 1.69Gy vs 2.72Gy and rectum of 0.24Gy vs 2.55Gy. On the 

poster we show hard copy images and more detailed results. 

Conclusions: Multichannel intrauterine applicators offer CTV and OAR dosimetric 

advantages over cervix applicators. Image guided 3-D planning simplifies 

the complex Madison intrauterine dosimetry system. Choosing traditional 

cervix cancer ICRU-38 and GEC/ESTRO dose points estimates OAR doses 

that can be compared with the large body of established data from cervix 

cancer which improves treatment safety. 

577 poster 

THE EFFECT OF PATIENT POSITION ON THE DOSE DISTRIBUTION 

OF INTRACAVITARY BRACHYTHERAPY FOR CERVICAL CANCER: 

THREE DIMENSIONAL COMPUTERIZED TOMOGRAPHY PLAN 

EVALUATION AND IN VIVO DOSIMETRIC STUDY. 

F. Colak 1 , M. Cengiz 2 , D. Yildiz 2 , E. Haciislamoglu 1 , A. Dogan 2 , G. 

Ozyigit 2 , F. Yildiz 2 

1 

KARADENIZ TECHNICAL UNIVERSITY, FACULTY OF MEDICINE, Radiation 

Oncology, Trabzon, Turkey 

2 

HACETTEPE UNIVERSITY, FACULTY OF MEDICINE, Radiation Oncology, 

Ankara, Turkey 

Purpose: The impact of leg position on the dose distribution during intracavitary 

brachytherapy for cervical cancer was evaluated in this study in order 

to determine whether there is an organ or applicator movement due to leg 

position. 

Materials: This prospective study was performed on 11 women with cervical 

cancer who underwent intracavitary brachytherapy. After insertion of 

brachytherapy applicator, serial computerized tomography slices with 5 mm 

thickness were taken from each patients. Two sets of CT slices were taken 

including pelvis, one with straight leg and the other with bended leg position 

with knee support. The target and critical organs were delineated by radiation 

oncologist. The dose (7 Gy) prescibed to point A. Radiotherapy plan 

was run on the Plato Planning Software System V14.1 (Nucletron Inc, NL) to 

get the dose distributions, dose-volume histograms, and the maximum dose 

points. Besides, rectum and bladder doses were measured in both leg positions 

during treatment by Scanditronix in-vivo dosimetry system (IBA Dosimetry 

Inc, Germany). The doses and volumes of organs were compared with 

Wilcoxon Signed Ranks test by using SPSS 11.5 statistical software (SPSS 

Inc, Chicago, IL). 

Results: No significant difference regarding the dose distributions and volumes 

of target, sigmoid and bladder due to leg position was observed neither 

on 3D planning nor in-vivo dose measurements. However, there were significant 

differences only for 25 and 50% isodose coverages of rectum in favor of 

straight leg position (p=0.026). There were no significant diffrences regarding 

maximum doses and in in any critical organ. The median maximum doses 

according to straight and bended leg positions respectively were as follows; 

5.28 Gy vs 5.59 Gy for rectum, 5.29 Gy vs 4.43 Gy for sigmoid colon, 7.23 

Gy vs 7.15 Gy for bladder (p>0.05). In vivo dosimetric measurements were 

also not significantly different between two positions. The median bladder and 

rectum doses were 3.92 Gy and 4.55 Gy for straight leg position and 4.15 Gy 

and 3.77 Gy for bended leg with knee support position, respectively (p>0.05). 

Conclusions: Change in leg position caused only small change in rectum 

dose distribution and did not cause any other change in both dose distributions 

and in vivo measured doses of both target and critical organs during 

cervical brachytherapy. The impact of this change should further be studied 

and patient comfort should also be considered for the appropriate patient 

positioning. 

578 poster 

THE EFFECT OF RECTAL RETRACTOR ON RECTAL DOSE IN 

GYNECOLOGICAL BRACHYTHERAPY APPLICATIONS 

N. Tuncel 1 , E. Dundar 1 , A. Inal 1 , M. G. Aksu 1 , A. F. Korcum 1 

1 AKDENIZ UNIVERSITY MEDICAL SCHOOL, Radiation Oncology , Antalya, 

Turkey 

Purpose: Since 2004, an in house designed rectal retractor tool and its fixation 

device have been used in gynecological brachytherapy insertions to reduce 

the rectum dose. In this study the effect of rectal retractor on doses of 

vaginal cuff, rectum and bladder were examined retrospectively. 

Materials: The dosimetric data of the patients who were treated using the 

Fletcher ovoid set of HDR Ir192 MicroSelectron brachytherapy unit were utilized 

at the Radiation Oncology Department of Akdeniz University Medical 

School. Between 2001 and 2003 the plans of the 109 brachytherapy insertions 

of the 33 patients treated without using the rectal retractor (Group I) and 

from 2004 to 2007 the plans of the 371 brachytherapy insertions of the 123 

patients treated with the rectal retractor (Group II) were evaluated. The orthogonal 

films were obtained at each fraction of the brachytherapy insertion 

by using SLS 23 SimCT unit. The vaginal cuff (Vk), rectum (Rg) and bladder 

(Bl) reference points were determined in Group I. In addition to these points 

another vaginal cuff reference point (Vk2) was defined to evaluate the effect 

of retractor on vaginal cuff dose in Group II. Treatment plans were made for 

each fraction with the BPS-V13.7 soft ware in Nucletron Plato treatment planning 

system. The dose normalization (%100) was performed to the catheter 

oriented lateral dose points (dps) which were defined laterally along the 1st- 

5th dwell positions (2.5 mm step size) of both ovoids at 5 mm deep into the 

vaginal surface.The prescribed dose at each fraction was 500cGy.The dose 

ratio of reference points according to the fraction dose was calculated for each 

fraction. The effectiveness of the rectal retractor implementations in patients 

were retrospectively investigated by comparing these data obtained from two 

groups. 

Results: Mean percent dose of reference points for each group was shown 

in table 1. Rectum and the bladder doses were decreased by 26.3% and 6% 

respectively while the vaginal cuff dose was increased by 7.1% with using the 

rectal retractor. The mean percent dose of Vk2 reference point was 97.5 in 

group II. 

Conclusions: The designed rectal retractor and its fixation device in gynecological 

brachytherapy applications have been used succesfully for decreasing 

the rectum dose without affecting the vaginal cuff dose.Figure 1: The applicators 

and the the reference points on AP (a) and lateral (b) films.

579 poster 

THE ROLE OF THE RADIOTHERAPY PHYSICIST IN INTRAOPER- 

ATIVE PARTIAL BREAST IRRADIATION USING A LOW ENERGY 

X-RAY SOURCE, BASED ON 10 YEARS CLINICAL EXPERIENCE 

C. Stacey 1 , M. Metaxas 1 , S. Morgan 2 , D. D’Souza 1 

1 

UNIVERSITY COLLEGE LONDON HOSPITALS NHS TRUST, Radiotherapy 

Physics, London, United Kingdom 

2 

ROYAL SUSSEX COUNTY HOSPITAL, Radiotherapy Physics, Brighton, 


Purpose: To describe the role of the radiotherapy physicist in the clinical implementation 

of the Intrabeam TM system for intraoperative radiotherapy (Carl 

Zeiss, Germany), based on 10 years experience at University College London 

Hospital. 

Materials: On delivery of the 50kVp electronic X-Ray system, the Radiotherapy 

Physics Group undertook acceptance and commissioning. Half-value 

layer measurements were made using a PTW 23342 0.02cc ion chamber. A 

dedicated water phantom was employed to measure variation of dose rate 

with radial distance from the X-Ray source in 5 orthogonal directions and 

in one direction for each of 8 spherical applicators. These measurements 

were compared with the manufacturer supplied QA peripherals and with radiochromic 

film to assess radial isotropy and output constancy and stability. 

A radiation protection survey and risk assessment was performed for unshielded 

surgical theatres prior to clinical introduction. The routine physics 

requirement comprises: pre-treatment QA and calculation of applicator treatment 

times; in theatre: actively delivering and monitoring the radiation treatment, 

monitoring and enforcement of staff radiation protection in and around 

the theatre and measurement of patient skin dose by TLD. 

Results: UCLH physicists have commissioned 4 such X-Ray sources for clinical 

use. We have treated 134 patients over a period of 10 years. To date, 

dose rate surveys during treatment have demonstrated the safe usage of the 

system under controlled conditions and no member of staff has had a recordable 

radiation dose. 

Conclusions: The Intrabeam TM device has been shown to be very stable 

dosimetrically and also practical within a standard clinical environment. The 

involvement of the radiotherapy physicist in the commissioning and clinical 

implementation of this intraoperative radiotherapy system is imperative to ensure 

safe treatment delivery and radiation protection of staff and patients. 

580 poster 

THREE OR FOUR FRACTIONS PER WEEK IN POSTOPERATIVE 

HIGH DOSE RATE BRACHYTHERAPY (HDRBT) FOR ENDOME- 


S 191 

TRIAL CARCINOMA (EC) 

A. Rovirosa 1 , M. Vargas 1 , C. Ascaso 2 , A. Sánchez-Reyes 3 , F. Martinez 

1 , A. Herreros 1 , R. M. Francisco 1 , M. Piñeiro 2 , M. Arenas 4 , A. Biete 5 

1 HOSPITAL CLÍNIC, Radiation Oncology, ICMHO, Barcelona, Spain 

2 UNIVERSITY OF BARCELONA, Public Health Dpt., Barcelona, Spain 

3 CLINICA PLATON, Radiation Oncology Dpt., Barcelona, Spain 

4 HOSPITAL SANT JOAN DE REUS, Oncology Dpt., Tarragona, Spain 

5 HOSPITAL CLÍNIC, Radiation Oncology Dpt., Barcelona, Spain 

Purpose: To evaluate the HDRBT results in postoperative treatment of EC 

using a schedule of 3 or 4 fractions/week. 

Materials: Between June 03 and December 06, 89 patients (pts) were treated 

after surgery of EC with HDRBT (HDR Ir192, MicroHDR Nucletron projector). 

After surgery patients were staged using FIGO classification: 24 IB, 45 IC, 

4IIA, 6 IIB, 4 IIIA, 2 IIIB, 4 IIIC. Pathology: 77 endometrioid, 6 serous, 2 clear 

cell, 3 mixed types, 1 miscelaneous. Radiotherapy: 67/89 pts. received external 

beam irradiation (EBI) plus HDRBT (Group 1) and 19/89 pts. received 

exclusive HDRBT (Group 2). Group 1: EBI mean dose was 45 Gy (range 

44-50), 1.8-2 Gy/day, using 6 or 18 MV photons from a Linac; after EBI pts 

received HDRBT with 3 fractions of 4 to 6 Gy. Group 2: Pts received 6 fractions 

of 4 to 5 Gy. HDRBT dose was prescribed at 5 mm from vaginal surface 

and the applicators were colpostats in 6/89 cases and cylinders in 83/89 

cases (cylinder’s diameter were 2, 2.5, 3 and 3.5 cm). HDRBT was administered 

3 or 4 days per week regime when possible. Overall treatment time 

with HDRBT. Group 1: HDRBT was completed in a median time of 5 days 

in 32 pts (range 3 to 5) and in more than 5 days in 35 pts, median 7 days 

(range 6-23). Group 2: HDRBT was completed in less than 15 days in 11 pts, 

median 14 days (range 9-15) and, in 16 days or more in 11 pts, median 22 

days (range 16 to 28). Toxicity was evaluated using RTOG scores and it was 

performed the study of BED in vaginal mucosa surface. Statistics: Student’s 

t-test, Chi-square test & ROC curves. 

Results: Pts mean follow-up was 31 months (range 5.37-70.27). Only 1/89 

pts had vaginal relapse and died and 1/89 pts was lost in follow-up. Early 

toxicity appeared in 8/89 (9%) pts and was resolved; late toxicity appeared 

in 13/89 (14%): vaginal mucosa 7G1, 3G2, 1G4; bladder 2G1, 2G2; rectal 

2G1. No differences in toxicity were found in relation to the overall treatment 

interval time in Group 1 and in Group 2. Mean BED vaginal mucosa in pts 

receiving EBI was 63Gy (range 41-146) and in cases with HDRBT alone was 

118 Gy (range 82-198). Cases with G2 late vaginal toxicity received more 

than 60 Gy when pts had previous EBI and more than 120 Gy in pts treated 

by HDRBT alone. 

Conclusions: 1) Three fractions of 4-5 Gy administered in 3 to 5 days after 

EBI or 6 fractions in less than 15 days in patients receiving HDRBT alone 

seems a safe treatment in relation to toxicity and local control for EC. 2) A bigger 

number of patients are needed to probe a relationship of vaginal toxicity 

with BED. 

581 poster 

TOWARDS AN EFFICIENT AND ACCURATE HDR-BRACHYTHERAPY 

BOOST TREATMENT OF THE BREAST 

B. Schaeken 1 , C. Goor 1 

1 ZNA MIDDELHEIM, Radiotherapy, Antwerpen, Belgium 

Purpose: To develop an easy, fast and straightforward procedure for 

brachytherapy boost of breast cancer without compromising accuracy. To design 

new tools to meet this goal, so the overall treatment time can be reduced 

to approximately one hour. 

Materials: Only patients in whom the tumorbed is marked using metal hemoclips 

are applicable for this method. The patient is positioned exactly the 

same way as during the treatment for EBRT (breast plate Cablon; arms lying 

above the head using a bowl support). At first, the angle of the needle path 

is estimated on the dosimetry Ct scan used for the planning of the EBRT. 

We designed a special mechanical arm, equipped with the breast bridge for 

needle placement, which is mounted on the table top. The two opposing 

templates are each provided with a radio opaque marker to allow alignment 

under the desired angle using fluoroscopy. Thereafter the breast templates 

are rotated along the bridge’s axis to align needle entry holes with the position 

of the clips and chest wall. Two extra templates are mounted on top of the 

bridge, which are equipped with a needle guide tool that allows insertion of 

the needles one by one without bending. This way the conditions for the Paris 

System are guaranteed. All needles are inserted under local anaesthesia. A 

dosimetry CT scan with the breast implant (helix mode, 1 mm slices) is taken 

for definitive dose planning (Flexiplan, Isodose Control; 7 Gy @ DB, Dskin < 

3 Gy). Directly after the planning procedure, the patient is connected to the 

HDR-afterloader (Flexitron, Isodose Control) and treated. 

Results: Our new procedure resulted in a significant reduction of the overall 

procedure time: from 3 hours initially to 1 hour. The guidance system for needle 

insertion allows straightforward and safe insertion of all needles under the 

correct angle, without bending, maintaining parallelism of all needles which is 

confirmed on the CT images with breast implant. The whole treatment procedure 

can be done in an adequate and safe way, regardless the experience of 

the physician. 

Conclusions: Due to simple tools, we succeeded in simplifying this treatment

S 192 CLINICAL/DISEASE SITES : BREAST 

mode without making compromises on its quality. 

Clinical/Disease sites : Breast 

582 poster 

A 3% UREA LOTION PREVENTS DEHYDRATION AND DESQUAMA- 

TION AFTER RADIOTHERAPY. A DOUBLE-BLIND, RANDOMIZED, 

PLACEBO-CONTROLLED STUDY 

V. M. Reyes Lopez 1 , J. Coll 2 , M. Ramos 1 , A. Capdevila 2 , A. Mirada 2 , J. 

Giralt 1 

1 VALL D’HEBRON UNIVERSITY HOSPITAL, Radiation Oncology Department, 


2 ISDIN, barcelona, Spain 

Purpose: To determine the effectiveness of a 3% urea hydrating lotion for 

irradiated skin in reducing radiation induced, using non-invasive biophysical 

instrumental tests 

Materials: Double blind, randomized placebo-controlled, phase 3 trial, included 

women with resected breast cancer receiving adjuvant radiotherapy 

(RT) (conventional RT 1.80 Gy 5x week to a total dose of 50.4 Gy, with an 

optional boost up to 66.4 Gy). Subjects were randomized 1:1 to receive a hydrating 

lotion containing 3% urea, polidocanol and hyaluronic acid (group 1) or 

a placebo hydrating lotion with no active products (group 2). Patients applied 

the product throughout the course of the RT. Cutaneous toxicity was assessed 

clinically using the RTOG/EORTC scale and pigmentation and pruritus were 

recorded on scales of 0 to 3. The instrumental tests measured hydration 

(Corneometer 820 CM), transepidermal water loss (TEWL) (TEWAMETER- 

TM210), erythema (Colorimeter a*) and desquamation (D-Squam stripping 

and Colorimeter c*). The measurements were performed at the start of the 

RT, after 3 weeks, at the end of treatment, and 1 month after the end of treatment 

Results: Forty-eight patients were included and assigned to two groups 

(n=22 group 1 and n=26 group 2). Grade 3 acute skin toxicity was observed 

in 5,3% and 4,5%; there were no significant differences between the groups. 

There were no significant differences with regard to pruritus. Pigmentation 

was significantly greater in group 1 (p

Materials: 196 patients (pts) receiving adjuvant RT for breast cancer, treated 

between 2002 and 2007, were examined. 104 of them underwent 3D RT, 

while IMRT was performed in 92 patients. The clinical indication for IMRT 

was represented by unfavourable anatomic characteristics in 33 pts (35.8%) 

and, in 59 cases (64.1%), by the necessity to irradiate locoregional lymph 

nodes. All pts. were affected by breast carcinoma, stage 0 to III, surgically 

resected, and received sistemic therapy (chemotherapy, hormonotherapy, or 

nothing, according to stage). Radiation dose was the same in the 2 groups: 

it varied from 48.6 to 50 Gy to whole breast or chest wall (with daily fractions 

of 1.8-2 Gy). A total dose of 50 Gy on supraclavicular and eventually internal 

mammary chains and 54 Gy on the axilla, in case of nodal involvement, 

was delivered. The boost dose of 10-16 Gy on the tumor bed, according to 

margins status, was added. Besides the pts. were stratified, in respect of 

breast volume, into 2 groups:


the recurrence. We recommend using decision tree methods together with 

KaplanMeier analysis to determine risk factors and effect of these factors on 

survival. 

589 poster 

ASSESSING SOFT TISSUE DEFORMATION AND DOSIMETRIC 

DISCREPANCIES IN WHOLE BREAST IRRADIATION. THE USE OF 

CONE-BEAM COMPUTED TOMOGRAPHY TO VERIFY CURRENT 

TREATMENT PRACTICES. 

N. Anderson 1 , M. Wada 1 , K. Rykers 1 , M. Rolfo 1 , E. Zupan 1 , R. Height 

1 , M. Lawlor 1 , M. Feigen 1 

1 AUSTIN HEALTH, Radiation Oncology, Melbourne, Australia 

Purpose: Whole breast irradiation is dependent on external skin markers as 

a means of field verification. 2D verification is a commonly used method of 

treatment verification, based on image registration of chest wall and lung volumes 

using MV images. Elekta kV cone beam CT (CBCT) allows for 3D information 

to be collected throughout a course of radiotherapy. The kV imaging 

allows direct image comparison with planning CT data and enables the user 

to readily detect soft tissue discrepancies. In this study CBCT data is compared 

with planning CT data by co-registering kV data sets and by overlaying 

treatment beams on both datasets. Dosimetric impact, positional changes 

and soft tissue variation is quantified, and the current quality of breast irradiation 

is evaluated. 

Materials: 5 patients undergoing whole breast irradiation were used for analysis 

as part of a hospital ethics board-approved prospective study. Patients 

were CBCT scanned 8-10 times during their treatment course (50Gy in 25 

fractions). Patients were aligned using skin markings along the medial and 

posterior beam edges. These edges were defined with fiducial markers to allow 

for accurate field placement on the CBCT data sets. CBCT data sets were 

exported from the CBCT system to the planning system (CMS, XiO) and registered 

with the corresponding planning CT. Positional errors were recorded 

and beams were overlayed on the CBCT to determine the dosimetric impact 

of these errors. Bulk density corrections were applied to both planning and 

cone beam data sets, to negate the discrepancy in Hounsfield units between 

scans. A breast planning target volume (PTV) was established to assess the 

dosimetric consequences of the soft tissue errors. 

Results: Preliminary findings present dosimetric deviations to breast PTV 

mean dose of 0.04%, with a range of 0.02% to 1.7%. The 98% isodose 

coverage to the PTV (V98) presents a mean deviation of 2.4%, with a range 

of 0.7% to 9.5%. The 95% isodose coverage to the PTV (V95) presents a 

mean deviation of 1.2%, with a range of 0.04% to 2.2%. The maximum dose 

to heart mean was 4.3%, ranging from 1.5% to 15.1%. 

Conclusions: Results from this investigation give strong support to our current 

practices of whole breast irradiation. Dose discrepancies are small based 

on treatment plans being overlayed onto CBCT data sets. Organ at risk dose 

comparisons also present minor discrepancies. However, breast IMRT is an 

area of treatment planning and delivery that requires a high level of precision 

in treatment execution. Soft tissue discrepancies and positioning variation 

can have a considerable dosimetric impact on PTV coverage. CBCT may 

play a significant role in the quality assurance of breast IMRT, utilising the 

methodologies presented in this study. 

590 poster 

BREAST CONSERVING THERAPY WITH HIGH DOSE RADIOTHER- 

APY (60 GY) FOR MULTIFOCAL AND MULTICENTRIC BREAST 

CANCER 

A. Bonanni 1 , L. Marmiroli 1 , O. Caspiani 1 , F. Tortoreto 1 , G. Mazzarella 1 , 

M. Leone 1 , A. Petrone 1 , S. De Fazio 1 , C. Guidi 1 

1 SAN GIOVANNI CALIBITA HOSPITAL, Rome, Italy 

Purpose: Management of patients with multifocal or multicentric invasive 

breast tumor is still an area of breast cancer cure without unanimous agreement. 

Several authors agree that a clinical diagnosis is an indication to 

mastectomy, although a pathologic diagnosis, after quadrantectomy, is often 

treated with breast-conserving treatment. The objective of this study was to 

evaluate the characteristics and outcomes in terms of progression free survival 

(PFS) and toxicity, of women with multifocal or multicentric breast tumor 

treated at our institution with a high radiation dose (60 Gy) to the whole breast. 

Materials: We have retrospectively analyzed records from 870 patients 

breast cancer treated at Fatebenefratelli Hospital, Isola Tiberina (Rome) from 

January 2001 to June 2006. A total of 42 patients with multifocal or multicentric 

invasive breast tumor was identified who received breast conserving 

surgery plus postmastectomy radiation therapy, with or without chemotherapy. 

All patients were forewarned of the likely higher chances of cure with a 

mastectomy, but all of them refused. Patients were treated with irradiation of 

the breast, 60 Gy to the whole implicated breast without boost, with tangential 

fields; regional lymphatic stations were treated as indicated (50 Gy). 

Results: The median age of the 42 patients was 61 years (38 85); 34 had a 

multifocal breast tumor, 8 patients had a multicentric tumor. The pathological 

tumor’s stage was T1 in 36 patients, T2 in 5, T3 in 1; the nodal stage was 

N0 in 27, N1 in 11 and N2 in 4 patients. The histological subtype was ductal 

carcinoma in 29 cases and lobular carcinoma in 13 cases. 26 patients (62%) 

were treated with chemotherapy. With a median follow-up of 18 months (9 

60), the rate of loco-regional failure was 1/42 (2%) and the rate of distant 

metastases was 1/42 (2%); PFS was achieved in 40 patients (95%). WHO 

grade 3 acute skin toxicity was observed in 36% of patients; anyway, no difference 

in permanent cosmetic anomalies were observed, when compared to 

standard treatment. 

Conclusions: Patients with pathological multifocal or multicentric breast tumor 

treated with breast conserving surgery followed by high dose radiation 

therapy to whole breast (60 Gy) have a very good outcome in terms of locoregional 

control and disease-free survival. Our results indicate that the 

breast conserving treatment is a suitable option in this cohort of patients. 

591 poster 

BREAST-CONSERVATION TREATMENT WITHOUT ANY SURGICAL 

PROCEDURE USING NEWLY DEVELOPED ENZYME-TARGETING 

RADIOSENSITIZER CONTAINING HYDROGEN PEROXIDE & 

SODIUM HYALURONATE FOR BREAST CANCER PATIENTS 

Y. Ogawa 1 , K. Kubota 1 , H. Ue 1 , Y. Kataoka 1 , K. Miyatake 1 , M. Tadokoro 

1 , K. Tsuzuki 1 , T. Yamanishi 1 , S. Itoh 1 , S. Kariya 1 , J. Hitomi 1 , A. Tsuzuki 

1 , T. Sasaki 1 , N. Yokota 1 , N. Hamada 1 , M. Fukumoto 1 , A. Nishioka 1 

1 MEDICAL SCHOOL, KOCHI UNIVERSITY, Diagnostic Radiology Radiation 

Oncology, Nankoku, Japan 

Purpose: Using a currently used linear accelerator, we intended to inactivate 

peroxidase/catalase in a topical tumor tissue by the application of hydrogen 

peroxide, thus re-oxygenizing the tumor tissue by the oxygen produced by 

the hydrogen peroxide degradation. In this way, we can convert radioresistant 

tumors into radiosensitive ones. On the basis of this strategy, we have 

developed a new enzyme-targeted radiosensitization treatment named KOR- 

TUC I (Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas, Type 

I) using a hydrogen peroxide solution (Oxydol)-soaked gauze bolus for superficially 

exposed & unresectable neoplasms, such as malignant melanoma 

and malignant fibrous histiocytoma, based on our experimental results which 

demonstrated hydrogen peroxide as a strong radiosensitizer for a highly radioresistant 

osteosarcoma cell line. This newly developed radiosensitization 

treatment showed to be an effective & valuable method of radiosensitization 

in terms of the blockade of anti-oxidative enzymes such as peroxidases, resulting 

in local oxygen production. 

Materials: Based on our clinical experiences using KORTUC I, we also 

developed a new radiosensitizer containing hydrogen peroxide & sodium 

hyaluronate for topical tumor injection for various types of tumors which are 

not superficially exposed, and the method was named KORTUC II. The agent 

is composed of 0.5% hydrogen peroxide & 0.83% sodium hyaluronate, which 

is safe for injection into human tumor tissue, slowering the degradation of hydrogen 

peroxide & elonging the acting time by containing sodium hyaluronate 

for adding viscousity and avoiding irritation for human body. KORTUC II trial 

was accepted by our local ethical committee concerning of the injection for 

advanced bone/soft tissue malignant neoplasms, breast cancer of op.refused 

or aged patients, and metastatic lymph nodes. 

Results: Thirty two patients including 14 breast cancer patients (stage I: 2 

patients, stage II: 6, stage III: 3, and stage IV: 3) were enrolled in the KOR- 

TUC II trial upon fully informed consent. Especially concerning breast cancer 

patients, all of the tumors of 14 patients showed clinically complete response 

evaluated by PET-CT studies performed approximately 3 months following the 

KORTUC II treatment. The patients did not show any severe complications 

excluding mild dermatitis (grade I), and cosmetic results were excellent for 12 

of the 14. Patients under 75 years old also undertook systemic chemotherapy 

prior to the KORTUC II treatment, and patients with estrogen receptor-positive 

tumors also undertook hormonal therapy. None of the 14 patients have so far 

shown local recurrence, and the mean follow-up period at the end of February 

2008 was still short and 12.5 months. 

Conclusions: In conclusion, breast-conservation treatment without any surgical 

procedure can be performed by using our new enzyme-targeting radiosensitizer 

for topical tumor injection into the tumor tissue. 

592 poster 

BREATHING MOTION IN SUPINE AND PRONE BREAST CANCER 

RADIOTHERAPY: INTRA-FRACTION DISPLACEMENTS USING AN 

EPID IN CINE MODE ACQUISITION 

D. Gaudino 1 , S. Ramella 1 , G. Stimato 1 , F. Cellini 1 , M. Ciresa 1 , M. Fiore 

1 , C. Greco 1 , V. Altomare 2 , R. Carino 2 , A. Primavera 2 , D. Stagnitto 3 , R. 

Andrich 3 , R. M. D’Angelillo 1 , L. Trodella 1 

1 CAMPUS BIO-MEDICO UNIVERSITY, Radiotherapy, Rome, Italy 

2 CAMPUS BIO-MEDICO UNIVERSITY, Breast Unit, Rome, Italy 

3 S. GIOVANNI HOSPITAL, Breast Unit, Rome, Italy 

Purpose: To compare intra-fraction breathing motion in the same patient 

treated in supine and in prone positions. 

Materials: Each patient underwent virtual simulation with computed tomog-

aphy either in supine position (using breast board device) either in prone 

position (using an home made system for prone set-up to displace the controlateral 

breast away from the tangential field borders). Treatment planning was 

performed on both studies. Two optimized plan were runned using tangential 

field and were approved according to dosimetric constraints. During the initial 

three and the following three days, each patient was treated in supine and 

prone position, respectively. During the delivering of these treatment sessions, 

CINE acquisition mode was performed using Varian Electronic Portal 

Imaging device. Each images was acquired every 1,66 seconds from both the 

tangential fields. Displacements at the central axis between the isocenter and 

skin contour were measured by a single operator so to diminish inter-operator 

variability. 

Results: 1067 electronic portal images from 10 patients were collected and 

analyzed. EPI in supine and prone position were 60% and 40% of the total 

respectively. The reason of this unbalance is in the short duration of dose 

delivering in prone position due to reduced monitor unit compare with supine 

treatment (p


early stage left sided breast cancer. 

Materials: Plan analysis was performed for two groups of patients, with ten 

patients in each group. First group received FBIG, and second group DI- 

VBH RGRT course. In FBIG group, planning Computed Tomography (CT) 

study acquisition was performed using retrospective Four-Dimensional Computed 

Tomography (4DCT) technique. In DIVBH group planning CT study 

was acquired using prospectively gated CT scanning. For each group notgated 

CT study was obtained as well. Contouring of target volumes and 

normal anatomy, and treatment planning was performed on both CT studies, 

allowing direct comparison of the clinical parameters of not-gated and 

respiratory-gated treatment plans. Following clinical parameters were evaluated 

for treatment plans: mean heart dose, maximal heart dose, mean lung 

dose and maximal lung dose. 

Results: Significant heart sparing was observed for FBIG and DIVBH groups, 

as compared to non-gated plan of the same patients: mean heart dose was 

reduced by 43 and 45% in FBIG and DIVBH groups, respectively. However, 

DIVBH group had shown much lower maximal heart dose: it was reduced 

by 6 and 58% in FBIG and DIVBH groups, respectively. Maximal lung dose 

was not changed for both RGRT groups. All RGRT plans patients had shown 

significant reduction of mean lung dose in comparison with non-gated plans: 

14 and 25% in FBIG and DIVBH groups, respectively. DIVBH provided much 

better heart sparing as compared with DIVBH RGRT: mean heart dose and 

maximal heart dose in DIVBH group was lower by 46 and 56% respectively, 

than in FBIG group. DIVBH technique had also shown better lung sparing, 

as mean lung dose in this group was lower by 22% as compared with FBIG 

group. 

Conclusions: Both RGRT techniques (FBIG and DIVBH) provide significant 

heart sparing in comparison with non-gated radiotherapy techniques in postoperative 

breast radiotherapy for left-sided early stage breast cancer patients. 

Use of RGRT for breast irradiation allowed to achieve significant reduction of 

mean lung dose, so reducing potential lung toxicity. DIVBH RGRT is preferable 

for the clinical use, as it provides better heart and lung sparing, as compared 

with FBIG RGRT. 

596 poster 

CT-IMAGE BASED INTERSTITIAL HDR BRACHYTHERAPY (HDR- 

BT) BOOST IN THE CONSERVATIVE TREATMENT OF STAGE I-II 

BREAST CANCER 

M. Kubaszewska 1 , M. Dymnicka 2 , J. Skowronek 1 , A. Chichel 1 , M. 

Kanikowski 1 

1 GREATPOLAND CANCER CENTER, Brachytherapy, Poznan, Poland 

2 GREATPOLAND CANCER CENTER, Medical Physics, Poznan, Poland 

Purpose: We present the preliminary findings of our protocol treating the 

tumor bed as a boost after BCS in selected patients with early-stage breast 

cancer treated with interstitial High Dose Rate (HDR) BT based on CT image 

procedure. 

Materials: Between January 2006 and August 2007, a total of 58 female 

patients with stage I to II breast cancer underwent BCS. This therapeutic 

procedure consist of a conservative surgical procedure, external irradiation of 

entire breast and a boost of additional irradiation to the tumor bed. All patient 

received boost using interstitial BT via flexible implant tubes. The boost dose 

was 10 Gy in each case. Pre-implant of CT scans were performed in order 

to localize surgical clips and define the tumor cavity. The target volume was 

determined as the clipped excision cavity with a margin of 2 cm and marked 

on the breast’s skin. 

Results: The skin dose didn’t exceed 60% of prescribed dose (it was fulfilled 

when superficial plane was implanted at least 10 mm from the skin). The evaluations 

involved the use of: cumulative dose-volume histograms (DVH), the 

high dose volumes calculation (V150%, V200%), the mean volume encompassed 

by the 100% reference isodose surface (V100%), the dose uniformity 

ratio (DNR), defined as the ratio of the 150% high dose volume (V150%) to 

the 100% reference dose volume (V100%) and the method of dose optimization 

procedure. 

Conclusions: 1. Accurate tumor bed delineation should be an important goal 

of brachytherapy boost treatment planning. 2. The use of surgical clips and 

CT together seems to be the best method to determine the target volume, 3 . 

Two sets (pre-implant and post-implant) of CT scans are required to improve 

the implant quality. 4. CT based BT boost treatment planning is useful tool 

to avoid geographical miss. 5. The irregular 3-D shape of the target volume 

and the normal tissue structures can only be localized correctly on the basis 

of visual information obtained from cross-sectional CT-imaging (better local 

control rate with less side effects might be achieved with these technique 

based on CT-imaging). 

597 poster 

DOSE TO DIFFERENT CARDIO-VASCULAR STRUCTURES DURING 

BREAST IRRADIATION 

M. Aznar 1 , S. Korreman 1 , G. Persson 1 , A. Pedersen 1 , M. Josipovic 1 , L. 

Specht 1 

1 COPENHAGEN UNIVERSITY HOSPITAL, Department of Radiation Oncology, 

Copenhagen, Denmark 

Purpose: Adjuvant radiotherapy for breast cancer can lead to risk of late cardiac 

complications. The Danish Breast Cancer Cooperative Group (DBCG) 

recommends that the volume of heart receiving more than 40 Gy be kept below 

5%, and the volume receiving more than 20 Gy be kept under 10%. When 

a portion of the heart is included in the radiotherapy field, the highest doses 

are likely to be to the anterior heart, especially to the left anterior descending 

coronary artery (LAD). This is a concern since new evidence suggests that 

arteries are particularly sensitive to radiation [1] and the LAD is one of the 

typical sites of origin for ischaemic heart disease. The purpose of the present 

work is to assess the acceptability of left-sided breast treatments with respect 

to the doses delivered to the heart and the LAD in each patient. 

Materials: In our clinic, the arch of the LAD is routinely contoured by the radiation 

oncologist and is used as a surrogate for evaluation of heart irradiation. 

The whole heart was retrospectively contoured on 24 patients for research 

purposes. All patients were treated with respiratory gated radiation therapy 

in the inspiration phase of breathing. The LAD was considered to receive a 

high dose when over 5% of the contoured volume received more than 20Gy. 

Results: For 4 out of 24 patients, the volume of heart irradiated was well 

below the threshold recommended by the DBCG whereas a high dose was 

still being delivered to the LAD. In one case, the dose to the LAD was low 

while 19% of the contoured heart volume received over 20 Gy. Results for 

two different contouring strategies of the LAD will also be discussed. 

Conclusions: Our experience indicates that it is not sufficient to calculate the 

dose to the heart as a whole organ: the dose to the LAD should also be considered 

when investigating the acceptability of a breast irradiation treatment. 

[1] Schultz-Hector S, Trott KR. Radiation-induced cardiovascular diseases: is 

the epidemiological evidence compatible with the radiobiological data? Int J 

Radiat Biol Phys 2007, 67:10-18

598 poster 

ESTABLISHMENT AND IMPLEMENTATION OF COMMON GUIDE- 

LINES FOR 3D TREATMENT PLANNING FOR BREAST CANCER IN 

SOUTHERN AND WESTERN SWEDEN 

L. Wittgren 1 , C. Björksund 2 , R. Chakarova 3 , K. A. Johansson 3 , P. 

Malmström 4 , P. Nilsson 5 , P. Karlsson 6 

1 

UNIVERSITY HOSPITAL UMAS, Dept of radiation physics, Malmö, Sweden 

2 

CENTRALLASARETTET, Medicinsk fysik och teknik, Växjö, Sweden 

3 

SAHLGRENSKA UNIVERSITY HOSPITAL, Dept of radiation physics, 


4 

LUND UNIVERSITY HOSPITAL, Department of Oncology, Lund, Sweden 

5 

LUND UNIVERSITY HOSPITAL, Radiation Physics, Lund, Sweden 

6 


Purpose: The purpose of this study was to introduce individual 3D-based 

treatment planning for all breast cancer patients receiving radiotherapy after 

mastectomy or after breast conserving surgery radiotherapy departments in 

West and South of Sweden (5 centres, 3 million inhabitants). This was accomplished 

by identifying common target definition templates and a common 

radiation technique for all participant clinics. 

Materials: Common guidelines regarding target definition and treatment 

planning techniques have been established utilizing 3D-treatment planning 

after mastectomy or after breast conserving surgery. Three different clinical 

situations were considered; treatment of breast after breast conservation 

surgery, treatment of breast and loco-regional lymph nodes after breast conservation 

surgery and chest wall and loco-regional lymph nodes after mastectomy. 

For each clinical situation the priority of the target volumes and organs 

at risk were defined as well as detailed requirements on the calculated 

dose distributions. Treatment planning techniques were suggested in order 

to fulfil these requirements. To verify the implementation of the guidelines a 

dummy run procedure regarding target outlining and treatment planning was 

performed. This was done in order to check compliance to the protocol at 

the participating centres and to find ambiguities in the instructions. At three 

separate occasions data were collected regarding all patients treated at the 

different centres during one month (200 patients). 

Results: Common guidelines for breast cancer radiotherapy were established 

and implemented to all patients treated in southern and western Sweden. 

Anatomical guidance for outlining of target volumes based on the risk 

for developing a recurrence was established. Further, priorities of target volumes 

and organs at risk regarding dose distributions and dose constraints 

were defined. The evaluation of 200 patients and the results from the dummy 

run proved the applicability of the guidelines. 

Conclusions: By a multidisciplinary approach new guidelines was established 

and the implementation was proved successful by evaluation of patient 

data as well as a dummy run procedure. The prospective approach of establishing 

and implementing these guidelines will enable future evaluation of 

both treatment results and side effects in relation to the given absorbed doses 

to different organs. 

599 poster 

EVALUATION OF THE SIZE AND POSITION OF THE TUMOR 

BED BY THE SURGICAL CLIPS DURING POST-LUMPECTOMY 

RADIOTHERAPY 

M. S. Thomsen 1 , B. Offersen 2 , M. Overgaard 2 

1 AARHUS UNIVERSITY HOSPITAL, Medical Physics, Aarhus C, Denmark 

2 AARHUS UNIVERSITY HOSPITAL, Oncology, Aarhus C, Denmark 

Purpose: The Danish Breast Cancer Group (DBCG) recommends that postlumpectomy 

radiotherapy in patients younger than 50 years includes a boost 

to the tumor bed. In the pre-CT era, this boost was planned on the simulator 

immediately prior to the start of boost treatment. Now, a CT scan is acquired 

for planning of the whole breast fields. If this scan also is going to be used for 

planning of the boost treatment it is required that the size and position of the 

tumor bed is unchanged during treatment. The purpose of this study was to 

investigate if there are any changes in the size and position of the tumor bed 

visualized by the surgical clips during whole breast irradiation . 

Materials: In the period July 2006 to December 2007, 35 patients with a 

mean breast volume of 604 cm 3 (median 545 cm 3 , range 132-1517 cm 3 ) and 

at least 3 surgical clips marking the tumor bed were CT scanned in the same 

position for both whole breast planning and boost planning. The mean number 

of days between the two planning CT scans was 39 days (range 28-49 

days). The average number of days between the lumpectomy and the first 

CT scan was 155 days (median 175 days, range 32-219 days) reflecting that 

a large proportion of these patients received chemotherapy prior to radiotherapy. 

The positions of the surgical clips were determined on both CT scans. 

This was carried out by measuring the position of the clips in a three dimensional 

coordinate system and determine the distance of each clips from the 

origin of the coordinate system. Furthermore, the distance of the clips from 

the skin surface was determined. 

Results: The sum of clips distances in each CT scan was calculated. The 

mean difference between the sum of clips distances in the first and the second 

CT scan was found to be +2.9 mm (median 2.5 mm, range -3.2 - 24.9 

CLINICAL/DISEASE SITES : BREAST 

S 197 

mm). The positive sign shows that the mutual distance between the clips 

was larger in the first CT scan than in the second CT scan. The mean difference 

between the depths of the clips below the skin surface between the two 

CT scans was 0.0 mm (median 0.3, range -3.8 - 4.8 mm).The two patients 

with largest changes of clips distances were scanned 32 and 36 days after 

lumpectomy. For one of these patients, it was found that one of the clips had 

migrated between the two scans whereas the positions of the 3 other clips 

did not change. For the other patient, some shrinkage of the tumor bed was 

observed. This indicates that changes in clips positions are possible if radiotherapy 

is initiated shortly after lumpectomy. However, the observed change 

is shrinkage resulting in a larger boost ctv if based on the primary CT scan. 

For the other patients where radiotherapy was started more than 60 days after 

lumpectomy no significant change of tumor bed was observed. 

Conclusions: The CT scan acquired for planning the whole breast fields may 

also be used for planning of the boost treatment. 

600 poster 

HEALTH TISSUE SPARING IN EARLY STAGE BREAST CANCER 

TREATED WITH SINGLE SHOT EXTERNAL BEAM PARTIAL BREAST 

IRRADIATION (PBI) WITH PATIENTS IN PRONE POSITION 

C. Giordano 1 , S. Arcangeli 1 , P. Pinnaro 1 , V. Landoni 1 , G. Iaccarino 1 , G. 

Arcangeli 1 

1 REGINA ELENA CANCER INSTITUTE, Radiotherapy, Roma, Italy 

Purpose: This study reports the feasibility of a new simple external beam 

technique to treat the tumour area in early stage breast cancer after conservative 

surgery. 

Materials: Patients with T1-2 N0-1 breast cancer, age ≥ 48 years, postmenopausal 

status, histologically proven non lobular carcinoma of the breast, 

primary tumour ≤ 3 cm, negative surgical margins, negative sentinel nodes 

or < 4 positive axillary nodes, no extracapsular extension, were recruited for 

this study. CT planning and treatment were performed in prone position on a 

dedicated couch. CTV (Clinical Target Volume) was identified by the surgical 

clips with a 1.5-2.0 cm margin. A dose of 21 Gy was delivered in a single 

session. 

Results: 50 patients entered this study. The meadian PTV (Planning Target 

Volume) and ipsilateral breast volumes (IBV) were 91 cm3 and 867 cm3, 

respectively, with a PTV/IBV ratio of 11%. The patients compliance was excellent. 

Few patients developed a mild, localized dermatitis, and none experienced 

lyponecrosis. 

Conclusions: Full dose, single fraction external beam radiotherapy is a simple 

and safe method to deliver postoperative treatment after breast conserving 

surgery. 

601 poster 

INITIAL QA AND CLINICAL EXPERIENCE OF BREATHING ADAPTED 

RADIOTHERAPY. 

C. Thornberg 1 , W. Ottosson 2 , S. Ceberg 3 , L. Wittgren 1 , S. Bäck 1 

1 

MALMÖ UNIVERSITY HOSPITAL, Radiation Physics, Malmö, Sweden 

2 

COPENHAGEN UNIVERSITY HOSPITAL, HERLEV, Oncology, Division of 

radiophysics, Herlev, Denmark 

3 



Purpose: In order to reduce radiation dose to heart and lung from external radiotherapy 

of left side breast cancer, breathing adapted radiotherapy (BART) 

was introduced in our clinic in 2007 as an end-inspiration gating technique. 

Since November 2007, 40% of all breast cancer patients were treated with 

the new gating technique. The purpose of this study was to present results 

and experiences from the QA tests before implementation of the technique, 

as well as some clinical experience considering further QA, tolerances and 

patient handling. 

Materials: The BART system consists of Varians real time positioning system 

(RPM) using a box with reflecting markers, placed on the chest and tracked 

by an infrared camera. The real time breathing pattern is used to establish the 

gating parameters. Before implementation, a series of tests were performed 

including i.e accelerator output, dosimetry, linearity, lowest number of MU:s 

acceptable, flatness and symmetry. A moving phantom was used to evaluate 

the geometry of objects in the reconstructed CT slices. The influence of motion 

on dosimetric aspects of the beam was investigated using a linear diode 

array detector system, LDA 99 (IBA Dosimetry), and an in-house built breathing 

robot simulating respiratory motion. Identical irradiations were performed 

using the respiratory robot with a) the detector in a fixed position in an uninterrupted 

beam, b) the detector moving with the robot in an uninterrupted 

beam, and c) the detector moving, only irradiated when its position was in the 

simulated end-inspiration phase. Finally, CT-studies for fifteen patients were 

acquired both with respiratory gating and during free breathing. To evaluate 

the benefit from BART, treatment plans were optimised for both CT studies. 

Results: The results of the QA measurements before implementation of the 

system were within limits suggested by the manufacturer. The linearity of 

the dose per MU had a maximum deviation of 0.7%. The symmetry of the


beam was maximum 1.8% and flatness showed a value of maximum 5.1 % 

for a clinically relevant number of MU:s (10-15). In measurements with the 

LDA99 and the breathing robot, gated and static profiles agreed well, with a 

difference in FWHM within 1.1 mm (figure 1). The dose smearing effect was 

insignificant for the investigated gating window. The stability of the system 

when tracking a box without respiratory movement was within 1.5 mm. The 

discrepancy between the true length of the breathing phantom and its length 

in the reconstructed CT images was within 3 mm. The reduction in average 

dose to the heart was around 50% as a mean for 15 patients. 

Conclusions: The BART technique was successfully integrated as an efficient 

way of reducing mainly heart doses to patients with left-sided breast 

cancer. The results of the initial QA tests of the performance of the accelerator 

and CT scanner was satisfactory. 

602 poster 

INTEROBSERVER VARIABILITY IN TARGET VOLUME DELINEATION 

OF BOOST VOLUME IN BREAST IRRADIATION ACROSS INSTITU- 

TIONS 

C. van Vliet-Vroegindewij 1 , A. van Mourik 1 , D. Minkema 1 , J. Duppen 1 , H. 

Bartelink 1 , P. Elkhuizen 1 

1 THE NETHERLANDS CANCER INSTITUTE/ANTONI VAN LEEUWENHOEK 


Purpose: To determine the interobserver variability of target volume delineation 

of boost volumes in tangential breast irradiation across several institutions 

and including patients with different amounts of seroma. 

Materials: Thirteen radiation oncologists from eleven different institutions delineated 

the volumes of surgical area, CTV boost and PTV boost of two leftsided 

and three right sided breast cancer patients. All observers used a written 

instruction and had access to all clinical available information, such as 

mammogram, MRI and patient file. Three patients had no seroma (patient 

1-3), one patient had some seroma (patient 4) and one patient had a clearly 

visible seroma (patient 5). The conformity index (CI) of two delineated structures 

(defined as the ratio of the overlapping volume and the encompassing 

total delineated volume) was used to quantify the difference in delineation 

between observers. The average CI of a patient is defined as the average 

of the CI’s for all combinations of two observers over that specific patient. A 

CI of 1 indicates perfect overlap. For all patients a median delineation was 

defined by the volume consisting of all pixels that were delineated by at least 

50% of the observers. Interobserver variation was evaluated by calculating 

the root mean square (RMS) distance between the median surface and each 

individual surface. To pinpoint specific areas of variation the median was subdivided 

in several anatomic regions: caudal, cranial, lateral, medial, dorsal, 

ventral and skin. 

Results: A large variety in the delineated volumes can be observed (Table 

1). In general, some observers consistently delineated larger volumes than 

the median volume for all patients, while others were consistently delineating 

smaller than the median volumes. The CI values reported showed a correlation 

with the presence of seroma. When seroma was hardly present, average 

CI-values below 0.5 were found, whereas in the case of a clearly visible 

seroma an average CI-value of 0.8 was found Contrary to our expectations, 

hardly any variations in average RMS distance were found over the different 

anatomic regions. 

Conclusions: Significant interobserver variations were found in the delineated 

volumes. The presence of seroma resulted in low interobserver variations. 

Regardless of the presence of seroma, none of the directions showed 

a significantly larger variation than the others. 

603 poster 

INTERSTITIAL HIGH DOSE RATE (HDR) BRACHYTHERAPY FOR 

DUCTAL CARCINOMA IN SITU OF THE BREAST : 5 YEAR RESULTS 

OF 38 CASES USING MULTI-CATHETER TECHNIQUE 

S. Biggs 1 , R. Mark 1 , P. Anderson 1 , T. Neumann 1 , M. Nair 1 , R. Akins 2 , 

S. Gurley 1 , D. White 1 

1 JOE ARRINGTON CANCER CENTER, Radiation Oncology, Lubbock, USA 

2 UNIVERSITY OF MIAMI, Department of Radiation Oncology, Miami, USA 

Purpose: External Beam Radiation Therapy (EBRT) has been the standard 

of care for breast conservation radiation therapy, in both Invasive Ductal Carcinoma 

(IDC) and Ductal Carcinoma In Situ (DCIS). Recent data indicates 

that Interstitial Implant and High Dose Rate (HDR) radiation afterloading compares 

very favorably to EBRT in selected cases of IDC. There is little data 

regarding HDR in DCIS. We report our HDR results in 38 patients with DCIS. 

Materials: Patients with Tis, T1, and T2 tumors measuring < 3 cm, negative 

surgical margins, and negative axillary lymph nodes were judged to be candidates 

for Interstitial Implant. Implants were performed under Stereotactic 

Mammographic guidance with conscious sedation and local anesthesia. The 

implants were placed using the Anderson-Nair Template using from 3 to 8 

planes, and 8 to 62 needles. Catheters were subsequently threaded thru the 

needles, and the needles removed. Catheter spacing was 1.0 to 1.5 cm. Radiation 

Treatment planning was performed using CT Scanning and the Plato 

System. Treatment volumes ranged from 25 cm3 to 359 cm3. HDR treatment 

was given using the Nucletron afterloading system. The breast implant 

volume received 3400 cGy in 10 fractions prescribed to the Planning Target 

Volume, given BID over 5 days. 

Results: Between 2000 and 2008, 167 patients underwent Interstitial HDR 

Implant. The procedure was well tolerated. No patient required hospital admission. 

With a median follow-up 56 months (range 6-98 months), local recurrence 

(LR) occurred in 3.0% (5/167). LR occurred in 2.3% (3/129) of patient 

with IDC vs. 5.2% (2/38) in DCIS (p = 0.32). Cosmetic results were good 

to excellent in 88.0% (147/167) of the patients. There were no infections. 

Wound healing complications developed in 4.8% (8/167). Three of these patients 

had received anthracycline based Chemotherapy. The other five had 

large (> 200 cm3) implant volumes, catheter spacing of 1.5 cm, and V-150% 

of > 30%. Two patients healed after 6 months of conservative treatment. 

Surgery was required in six patients who developed fat necrosis. 

Conclusions: With median 56 month follow-up, Breast Conservation radiation 

therapy utilizing Interstitial Multi-Catheter HDR Implant has yielded local 

recurrence rates and cosmetic results which compare favorably to EBRT in 

selected patients. There was no difference in LR between patients with IDC 

and DCIS. Treatment with anthracycline based Chemotherapy, large (> 200 

cm3) implant volumes, and V-150% > 30%, appear to be relative contraindications 

to Interstitial HDR Implant. Finally, catheter spacing of 1 cm yielded 

optimal dosimetry and minimized complications.

604 poster 

INTERSTITIAL HIGH DOSE RATE (HDR) BRACHYTHERAPY FOR 

EARLY STAGE BREAST CANCER : A REPORT OF 167 CASES 

USING MULTI-CATHETER TECHNIQUE 

P. Anderson 1 , R. Mark 1 , T. Neumann 1 , M. Nair 1 , D. White 1 , S. Gurley 1 


Purpose: External Beam Radiation Therapy (EBRT) has been the standard 

of care for breast conservation radiation therapy. Recent data indicates that 

Interstitial Implant and High Dose Rate (HDR) radiation afterloading compares 

very favorably to EBRT in selected patients. 

Materials: Patients with Tis, T1, and T2 tumors measuring < 3 cm, negative 

surgical margins, and negative axillary lymph nodes were judged to be candidates 

for Interstitial Implant. Implants were performed under Stereotactic 

Mammographic guidance with conscious sedation and local anesthesia. The 

implants were placed using the Anderson-Nair Template using from 3 to 8 

planes, and 8 to 62 needles. Catheters were subsequently threaded thru the 

needles, and the needles removed. Catheter spacing was 1.0 to 1.5 cm. Radiation 

Treatment planning was performed using CT Scanning and the Plato 

System. Treatment volumes ranged from 25 cm3 to 359 cm3. HDR treatment 

was given using the Nucletron afterloading system. The breast implant 

volume received 3400 cGy in 10 fractions prescribed to the Planning Target 

Volume, given BID over 5 days. 

Results: Between 2000 and 2008, 167 patients underwent Interstitial HDR 

Implant. The procedure was well tolerated. No patient required hospital admission. 

With a median follow-up 56 months (range 6-98 months), local recurrence 

occurred in 3.0% (5/167). Cosmetic results were good to excellent 

in 88.0% (147/167) of the patients. There were no infections. Wound healing 

complications developed in 4.8% (8/167). Three of these patients had 

received anthracycline based Chemotherapy. The other five had large (> 200 

cm3) implant volumes, catheter spacing of 1.5 cm, and V-150% of > 30%. 

Two patients healed after 6 months of conservative treatment. Surgery was 

required in six patients who developed fat necrosis. 

Conclusions: With median 56 month follow-up, Breast Conservation radiation 

therapy utilizing Interstitial Multi-Catheter HDR Implant has yielded local 

recurrence rates and cosmetic results which compare favorably to EBRT in 

selected patients. Treatment with anthracycline based Chemotherapy, large 

(> 200 cm3) implant volumes, and V-150% > 30%, appear to be relative contraindications 

to Interstitial HDR Implant. Finally, catheter spacing of 1 cm 

yielded optimal dosimetry and minimized complications. Compared to Mammosite 

technique, the Interstitial Multi-Catheter method offers greater flexibility 

of radiation delivery. Advantages include, no concern regarding surgical 

cavity shape irregularities, balloon conformality to surgical cavity, balloon 

rupture, balloon movement, air gaps, skin balloon proximity to skin, balloon 

shape distortion, and catheter movement within the balloon. 

605 poster 

INVESTIGATING THE EXPECTED EFFECTS OF PATIENT POSI- 

TIONING, BREATHING AND RADIATION PNEUMONITIS SCORING 

IN BREAST CANCER RADIOTHERAPY 

S. Hyödynmaa 1 , P. Mavroidis 2 , B. Costa Ferreira 3 , S. Axelsson 2 , N. 

Papanikolaou 4 , B. Lind 2 

1 

TAMPERE UNIVERSITY HOSPITAL, Department of Oncology, Pikonlinna, 

Finland 

2 

KAROLINSKA INSTITUTET AND STOCKHOLM UNIVERSITY, Department of 

Medical Radiation Physics, Stockholm, Sweden 

3 

UNIVERSITY OF AVEIRO, I3N Physics, Aveiro, Portugal 

4 

UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER, Department of 

Radiation Oncology, San Antonio, TX, USA 

Purpose: Of the most important parts of the radiotherapy process is accuracy 

in patient positioning and elimination of internal organ motion. Significant 

dose delivery discrepancies can contribute to a reduction of local tumor control 

and an increase of side effects. In this study, the expected effects of 

patient setup and breathing uncertainties characterizing three different irradiation 

techniques in breast cancer radiotherapy are investigated. 

Materials: Fifteen breast cancer patients are examined (5 resected with negative 

nodes (R-), 5 resected with positive nodes (R+) and 5 ablated). For the 

R- patients, two opposite tangential 6 MV photon wedge fields were used. For 

the R+ patients, a frontal photon field was added to the two tangential fields. 

The ablated patients were irradiated with two almost opposite anteroposterior 

photon fields and one electron field. Gaussian distributions are used to approximate 

the positioning uncertainties in the anteroposterior and craniocaudal 

directions. Breathing is assumed to have a linear behavior. The planned 

and delivered dose distributions are compared based on the complicationfree 

tumor control probability, P+ and the biologically effective uniform dose, 

(BEUD) concepts. 

Results: For the R- treatment plans, at the optimum dose levels of the corresponding 

dose distributions, the P+ values are 97.9% and 97.3%. The 

respective total control probabilities, PB are 99.3% and 99.1%, whereas the 

corresponding total complication probabilities, PI are 1.4% and 1.8%. For the 

R+ case and the corresponding dose distributions, the P+ values are 94.2% 


S 199 

and 93.0%, the PB values are 97.5% and 96.3%, whereas the PI values are 

3.3% and 3.3%, respectively. For the Ablation case and the corresponding 

dose distributions, the P+ values are 96.9% and 89.4%, the PB values are 

99.0% and 96.5%, whereas the PI values are 2.1% and 7.2%, respectively. 

In this case, for lung radiation pneumonitis Grade 1-2, the P+ values would 

change to 69.3% and 37.7%, respectively. 

Conclusions: Significant deviations between the planned and delivered dose 

distributions can be introduced by the combined effects of positioning uncertainties 

and breathing motion. The positioning and breathing uncertainties do 

not affect much the dose distribution to the CTV because they influence more 

the tissues lying at the edges of the irradiating fields. The delivered dose distributions 

show larger lung complication probabilities than the planned ones. 

606 poster 

LOCAL RECURRENCES AFTER BREAST CONSERVATIVE 

SURGERY ACCORDING TO DIFFERENT TIME PERIODS. 

A. Courdi 1 , E. Chamorey 2 , J. M. Ferrero 3 , E. Teissier 4 , F. Ettore 5 , M. 

Lallement 6 , J. Castelli 1 , I. Raoust 6 

1 CENTRE A. LACASSAGNE, Radiotherapy, Nice, France 

2 CENTRE A. LACASSAGNE, Department of Biostatistics, Nice, France 

3 CENTRE A. LACASSAGNE, Medical Oncology, Nice, France 

4 CENTRE AZURÉEN DE CANCÉROLOGIE, Radiotherapy, Mougins, France 

5 CENTRE A. LACASSAGNE, Pathology, Nice, France 

6 CENTRE A. LACASSAGNE, Surgery, Nice, France 

Purpose: To examine the rate of local recurrences (LR) in the ipsilateral 

breast after conservative surgery for breast cancer according to the time period 

of surgery. 

Materials: Patients treated with primary surgery from 1986 to 2002 were 

included in the study. Out of 2030 patients treated conservatively, 524 were 

operated before 1990 (group A), 683 between 1990 and 1997 (group B) and 

823 after 1997 (group C). All patients received post-operative radiotherapy. 

Chemotherapy and/or hormonal therapy was given according to the treatment 

policy at the time of presentation. In this study, follow-up was restricted to 5 

years for each time period to ensure an equal follow-up to each group. 

Results: The respective 5-year LR rates for these groups were 9.5%, 4.2% 

and 2.7% (p < 0.0001). The respective percent pT1 tumours were 82.1%, 

79.4% and 83.5%. To investigate whether the better results in recent years 

were related to smaller size at presentation, we have studied the outcome of 

pT1 tumours in each group. The respective rates of LR were 9.3%, 4.0% and 

1.4% (p < 0.0001). The mean sizes (in mm ± SD) of pT1 tumours were 13.6 

± 4.5, 13.1 ± 4.9 and 12.7 ± 4.9 for groups A, B and C respectively (p = 

0.03). To test whether this difference could have affected LR in the different 

groups, we analysed the 5-year LR of tumours measuring between 13.6 and 

18 mm (13.6 + 1 SD) vs tumours between 12.7 and 7.8 mm (12.7 1 SD) 

in the whole population. There was no statistical difference between the 2 

groups with 5-year LR of 5.3% and 4.6% respectively (p = 0.58). 

Conclusions: The rate of LR after conservative surgery for breast cancer 

has considerably decreased for patients treated in recent years. This was 

not solely the result of smaller tumour size at presentation, for at equal size, 

results were better in recent years. Rather progress in surgical procedures, 

more precise pathology reports (often requiring re-excision), higher quality 

and dose of radiotherapy and adequate hormonal therapy contributed to the 

improved results.


607 poster 

LONG TERM RESULTS OF BREAST CONSERVING OPERATION 

AND RADIATION THERAPY IN EARLY BREAST CANCER: A SINGLE 

INSTITUTIONAL EXPERIENCE 

J. H. Kim 1 , K. Ok Bae 1 , K. Sun Hee 2 

1 

DONGSAN MED CTR. KEIMYUNG UNIV, Radiation Oncology, Daegu, Korea 

Republic of 

2 

DONGSAN MED CTR. KEIMYUNG UNIV, General Surgery, Daegu, Korea 

Republic of 

Purpose: To evaluate long term results in terms of failure, survival and 

cosmesis after breast conserving operation and radiation therapy in early 

breast cancer. 

Materials: From January 1992 through December 2002, one hundred fifity 

five patients with early stage I and II breast cancer were treated with conservative 

surgery plus radiotherapy at Keimyung University Dongsan Medical 

Center. Age distribution was 25 to 72 years old with median age of 44. According 

to TNM stage, eighty eight were stage I, forty nine were IIa, and 

eighteen were IIb. Most patients underwent excision of all gross tumor and 

ipsilateral axillary dissection. Breast was irradiated through medial and lateral 

tangential fields of 6 MV photons to 50.4 Gy in 28 fractions over 5.5 

weeks. We delivered a boost irradiation dose of 10 to 16 Gy in 1 to 2 weeks 

to excision site. Adjuvant chemotherapy was administered in seventy six patients 

with several regimens such as CMF (cyclophosphamide, methotrexate, 

5-fluorouracil), AC (adriamycin, cyclophosphamide), FEC (5-FU, etoposide, 

cyclophosphamide). Adjuvant hormonal therapy was administered in ninety 

one patients with tamoxifen. Cosmetic results were assessed by questionnaire 

to patients grading of excellent, good, fair, poor. Follow-up periods were 

13 to 179 months with median 92 months. 

Results: Five year- and ten year-overall survival rate was 96.7% and 95.8%. 

Five year- and ten year- disease free survival rate (5YDFS, 10YDFS) was 

93.8% and 90.2%. According to stage, 5YDFS and 10YDFS was 95.1% and 

92.2%, 91.3% and 88.7%, 94.1% and 86.2% in stage I, IIa and IIb, respectively. 

Ten patients had distant metastasis and one had local and distant failure 

and one had local failure alone. Most of patients with distant metastasis 

had multiple metastatic sites with 45.5 months of median time to metastasis. 

Most common distant metastatic site was lung. Two patients with local failure 

had multiple recurrent foci in same breast at 11 and 40 months after radiation 

and were treated with mastectomy and chemotherapy. Three patients(1.9%) 

had an arm edema with 64 months of median time. One hundred nineteen 

patients answered our cosmetic result questionnaire and results were good 

to excellent in ninety six patients (80.6%). 

Conclusions: We considered that conservative surgery and radiation for the 

treatment of early stage invasive breast cancer had excellent survival and 

cosmetic results. 

608 poster 

LONG-TERM OUTCOME OF PATIENTS TREATED WITH BREAST 

CONSERVING SURGERY AND POST OPERATIVE RADIATION 

THERAPY FOR DUCTAL CARCINOMA IN SITU IN EDINBURGH 

CANCER CENTRE 1980-2000 

A. Stillie 1 , I. Kunkler 1 , G. Kerr 2 

1 

EDINBURGH CANCER CENTRE, Clinical Oncology, Edinburgh, United 

Kingdom 

2 

EDINBURGH CANCER CENTRE, Medical Statistics, Edinburgh, United 

Kingdom 

Purpose: Retrospective review to analyse the long-term outcome of patients 

treated with breast conserving surgery (BCS) and post operative whole breast 

radiation therapy (RT) for ductal carcinoma in situ (DCIS) in a single institution 

from 1980-2000. 

Materials: Case records of all patients with DCIS managed with BCS and 

post operative RT in Edinburgh Cancer Centre from 1980-2000 were retrospectively 

reviewed. Information was obtained to ascertain whether age at 

diagnosis, detection method, grade, margin status, presence of necrosis, and 

radiotherapy dose and fractionation had a significant effect on relapse and/or 

survival. Survival rates were calculated by the Kaplan Meier method and a 

multivariate Cox proportional hazards ratio was used to evaluate the significance 

of the aforementioned variables in relation to overall and relapse free 

survival. 117 patients were identified from the departmental database. 7 patients 

were excluded from the final analysis; 2 had previous invasive breast 

carcinomas and 5 did not receive radiotherapy until they developed loco regional 

recurrence of in situ or invasive disease. 110 patients were thus included 

in the final analysis. 

Results: The median age of patients was 56 (range 32-74). The majority, 

80%, had screen detected lesions. Median size of tumour was 15.4mm 

(range 2-40mm). Necrosis was present in 32%. Radial margins were >1mm 

in 81% of patients. All patients with radial margins ≤1mm underwent reexcision 

to ensure a final excision margin of >1mm. The majority of patients 

had high nuclear grade DCIS (54.5%). However the grade of DCIS was not 

documented in the pathology report of 42.7% of cases. The majority of patients 

(56.4%) received 50Gy in 25 fractions to the ipsilateral breast. 38.1% 

of patients received a RT boost to the tumour bed. At a median follow up 

of 84 months 15 patients (13.6%) developed loco regional recurrence in the 

ipsilateral breast; 4 DCIS and 11 invasive carcinoma. The 5 year relapse free 

survival was 94.8% and the actuarial 10 year relapse free survival was 86.0%. 

18 patients have died, of whom only one died of invasive breast carcinoma. 

The 5 year overall survival was 95.7% and 10 year actuarial overall survival 

90.3%. Age at diagnosis, time cohort, site of disease, detection method, 

margin status, presence of necrosis, and radiotherapy dose, in this cohort of 

patients, were not significant in relation to relapse free or overall survival. 

Conclusions: In conclusion the overall survival and relapse free survival of 

this single institution cohort of patients treated with BCS and RT for DCIS is 

consistent with published clinical trial data. 

609 poster 

LONG-TERM SEQUEL OF PROPHYLACTIC INTERNAL MAMMARY 

NODE IRRADIATION AFTER MASTECTOMY: AN INDIAN EXPERI- 

ENCE. 

S. Saha 1 , A. Gangopadhyay 1 , A. GhoshDastidar 1 , S. Ghorai 1 

1 MEDICAL COLLEGE HOSPITAL, Radiotherapy, Kolkata, India 

Purpose: There is no consensus regarding post-mastectomy adjuvant internal 

mammary node (IMN) irradiation in patients with medial or central quadrant 

breast cancer receiving anthracycline-based chemotherapy. The study 

aims to evaluate the benefit of inclusion of IMN during adjuvant radiotherapy 

as well as to analyze the cardiac effect amounting from radiation of this additional 

anatomical area. Study end points: locoregional recurrence, cardiac 

complications. 

Materials: After mastectomy with level II axilla dissection, IMN radiation was 

considered only in medial or central quadrant disease with axilla involvement. 

Between June 2000 and November 2002, 203 patients receiving post 

surgery chest wall radiation (50 Gy/25 fractions/5 wks), were randomized (after 

informed consent) to: Arm I- receiving additional IMN radiation (n=94; left 

breast: 43) and Arm II- no IMN radiation (n=109; left breast: 55). All patients 

received 6 cycles of FAC chemotherapy. CT-based planning was done for 

each patient to optimize IMN coverage. Volume of heart irradiated and the 

volume of heart receiving 5 Gy (V5) were estimated individually from integral 

DVH. Maximum heart distance (MHD) was measured for majority. All patients 

were monitored with ECG, Chest X-ray, Echocardiogram at the start of radiation, 

on completion and then 6 monthly. TMT and 24 hr. Holter monitoring 

were performed in selected cases. 

Results: After a median follow up of 72 months, 4 had chest wall recurrence 

2 of whom received IMN radiation. IMN recurrence was observed in none, 

whether they received IMN radiation or not. Regarding cardiac effects, 2 

patients of Arm I developed constrictive pericarditis. 3 had LV dysfunction 

(estimated by EF < 50%) and 3 developed congestive failure all belonged to 

Arm I with left sided disease. No toxicity was noted in 55 left breast cases of 

Arm II (p < 0.001). So significant late cardiac effect was observed in 8/43 left 

breast IMN -treated and in 0/55 left breast IMN- not treated cases (p

41% of patients underwent BCS, and 65% received adjuvant radiation therapy, 

with doses ranging from 26 Gy in 13 fractions to 50 Gy in 25, and 20% 

received an additional boost. 54% of patients received adjuvant chemotherapy. 

Overall, 51% of stages I-III patients experienced relapse, with a trend 

towards improvement in the last five years. The rate of LR recurrence in 

mastectomy patients was 21% and comparable to those treated with BCS followed 

by radiation (26%). Patients receiving 40 Gy or less adjuvantly seemed 

to have slightly more LR failures than those receiving >40 Gy (31% Vs 23%). 

The LR recurrence rate in the sub-group of patients who received a boost 

was 31% and similar to that of the sub-group who did not (30%). Mortality 

rates showed a trend towards improvement with time. 

Conclusions: This >40-year retrospective study represents one of the 

largest reviews of very young women with BC. These patients appear to 

present more frequently with poor prognostic markers when compared to 

older historical subsets of patients, likely resulting in the observed poorer outcomes. 

LR recurrence rates are particularly high and merit careful attention 

in further studies targeting this population. 

611 poster 

OPTIMIZATION IN PRONE BREAST RADIOTHERAPY AND SUB- 

GROUPS ANALYSIS 

S. Ramella 1 , G. Stimato 1 , D. Gaudino 1 , F. Cellini 1 , M. Ciresa 1 , M. Fiore 

1 , C. Greco 1 , D. Stagnitto 2 , R. Andrich 2 , V. Altomare 3 , A. Primavera 3 , R. 

Carino 3 , R. M. D’Angelillo 1 , L. Trodella 1 

1 CAMPUS BIO-MEDICO UNIVERSITY, Radiation Oncology, Rome, Italy 

2 S. GIOVANNI HOSPITAL, Breast Unit, Rome, Italy 

3 CAMPUS BIO-MEDICO UNIVERSITY, Breast Unit, Rome, Italy 

Purpose: To select subgroups of breast cancer patients who may benefit 

from prone-position technique for 3D conformal radiotherapy after conservative 

surgery. 

Materials: Thirty-eight patients with early breast cancer were divided into 

three groups according to target volume size measured in supine position: 

small ( ≤400cc), medium (400-700cc) and large (≥700cc). A second analysis 

was made up according to tumour location inside the breast quadrants 

(Upper/Lower and Outer/Inner). An home-made device was used for prone 

set-up to displace the controlateral breast away from the tangential field borders. 

All patients underwent to treatment planning computed tomography in 

both the supine and prone positions. Dosimetric data to explore dose distribution 

and volume of normal tissue irradiated were calculated for each patient 

in both positions. 

Results: Homogeneity index, hot spots areas, the maximum dose, and lung 

constraints (V5Gy, maximum lung distance and central lung distance) were 

significantly less in the prone position (p


cer. 

Materials: In MA Radiotherapy Center of Uludag University Medical Faculty 

Department of Radiation Oncology one hundred ninety eight patients 

threated with radiotherapy after breast conserving surgery during 1995-2005 

were evaluated retrospectively. Radiotherapy was applied 46-50 Gy with a 

daily fraction dose of 2 Gy for the whole breast , 16-20 Gy boost for the tumor 

bed and total dose completed was 66 Gy. Median age was 50 (range: 

28-85). One hundred and fifteen (58%) had stage I, 83 (42%) had stage II 

disease. The prognostic factors were analysed as the parameters associated 

with demografic, tumor and therapy. The program SPSS 13 was used for statistical 

analysis. The survival analysis were calculated with Kaplan-Meier Log 

Rank method and Cox regression models were applied to identify multivariate 

analysis for the factors that influence on survey. 

Results: During a median follow-up duration of 49 months (range: 2-137) 3 

patients (1,5%) developed local recurrence and 16 patients (8%) developed 

distant metastasis. No metastasis was detected in patients who developed 

local recurrence.Ten patients (50%) had died due to breast cancer and the 

other 10 patients had died because of comorbid illnesses. Five-year overall 

survival was 95% and disease-free survival was 86%. Age (p

618 poster 

QUANTITATIVE ASSESSMENT OF RADIATION-INDUCED NORMAL 

TISSUE TOXICITY USING ULTRASONIC IMAGING AND ULTRA- 

SONIC TISSUE CHARACTERIZATION: PRELIMINARY IN VIVO 

EXPERIENCE IN BREAST CANCER RADIOTHERAPY 

T. Liu 1 , J. Zhou 1 , S. Woodhouse 1 , P. Schiff 1 , L. Ballas 1 , G. Kutcher 1 

1 COLUMBIA UNIVERSITY MEDICAL CENTER, Radiation Oncology, New York, 

USA 

Purpose: Breast conservation therapy (BCT) has been shown to be equivalent 

to mastectomy in large clinical trials and has become the preferred treatment 

choice in women with early-stage breast cancer. Despite advances in 

radiation therapy technology, high doses of ionizing radiation often induce 

acute and late tissue toxicity. There is currently no objective means of measuring 

breast tissue injury/toxicity in the clinic. The purpose of this study is 

to investigate the use of ultrasonic imaging and ultrasound tissue characterization 

(UTC) to quantitatively evaluate normal tissue toxicity in breast cancer 

radiation treatment. 

Materials: A total of twenty-two breast cancer patients were enrolled in our 

study. All patients underwent lumpectomy followed by whole breast radiation 

of 50-50.4 Gy and an electron boost to the tumor bed of 10-16 Gy. Median 

follow up was 22 months (6-94 months). A clinical ultrasound scanner (Sonix 

RP system) with a linear array probe (L14-5/38) was used for data acquisition. 

Conventional B-mode images as well as the backscattered RF signals were 

captured simultaneously. The B-mode images show anatomical structure and 

the UTC technique extracts spectral features that are associated with properties 

of tissue microstructures. Three parameters of toxicity were measured 

in a quantitative fashion: skin thickness, Pearson correlation coefficient (assessing 

skin hypodermal layer toxicity), UTC midband fit (assessing breast 

glandular tissue toxicity). Statistical analysis was performed to correlate the 

UTC findings with clinical and patient assessments. 

Results: Ultrasound measurements for the treated breast were compared 

with the contra-lateral breast for quantitative assessment of normal tissue radiation 

toxicity. For all 22 patients the average thickness of the irradiated skin 

increased by 50% (p=0.005) and the average Pearson correlation coefficient 

of the irradiated hypodermis decreased by 35% (p=0.02). For the underlying 

glandular tissue, there were significant changes in the treated breast according 

to UTC midband fit (p = 0.002). Changes in midband fit were primarily 

related to soft tissue stiffness and correlated with the presence of fibrosis. 

The most severe radiation-induced toxicity consistently occurred in the tumor 

bed regions of the treated breast. The quantitative ultrasound measurements 

were consistent with the clinical breast toxicity evaluation and patient selfassessments. 

Conclusions: This study describes an advanced ultrasonic imaging method 

to quantitatively measure skin and subcutaneous tissue changes associated 

with breast cancer radiation therapy. Our ultrasonic technique can measure 

the extent and location of breast radiation toxicity. This tool will become increasingly 

valuable as we evaluate new strategies for breast cancer radiation 

therapy, such as hypo-fractionation and partial breast radiation therapy. 

619 poster 

RADIATION-INDUCED BRONCHIOLITIS OBLITERANS ORGANIZ- 

ING PNEUMONITIS SYNDROME AFTER BREAST-CONSERVING 

THERAPY 

E. Ogo 1 , C. Tsuji 1 , H. Suefuji 1 , G. Suzuki 1 , H. Etou 1 , C. Hattori 1 , T. Abe 

1 , N. Hayabuchi 1 

1 KURUME UNIVERSITY, Radiology, Kurume, Japan 

Purpose: We observed a rare and unique occurrence of radiation-induced 

pulmonary injury outside the tangential field for early breast cancer treatment. 

The findings appeared to be idiopathic and were called radiation-induced 

bronchiolitis obliterans organizing pneumonia (BOOP) syndrome. 

Materials: We conducted a retrospective analysis of 484 consecutive patients 

with early breast cancer undergoing tangential-field radiation therapy in 

our institution from January 1992 to February 2007. We observed more than 

one year after radiotherapy. Radiotherapy was administered by 4 MV photons 

in all patients. The patients underwent chest X-ray periodically. If we found 

the BOOP syndrome, we added chest computed tomography scans (CT ) and 

classified the characteristics of pulmonary lesions outside the radiation field. 


S 203 

Results: The incidents of the radiation-induced BOOP syndrome was 10 patients 

(2.1%; 10/484). Five of them had fever and cough, three had no symptoms. 

We did not find a relationship between the characteristics of patients 

and the occurrence of radiation-induced BOOP syndrome. The pulmonary 

lesions were classified into four patterns on the chest CT. Progression of the 

pulmonary lesions observed on chest x-ray was classified into three patterns. 

BOOP syndrome appeared within 5.6 months (2 to 12 months) after radiotherapy 

and completely disappeared within 5 to 12 months after its onset. 

Their clinical conditions were not severe and these pulmonary lesions disappeared 

gradually without use of steroid in our institution. There was no death 

caused by BOOP syndrome. 

Conclusions: Although the incidence of BOOP syndrome and its associated 

prognosis are not significant, the patient clinical condition must be carefully 

followed. 

620 poster 

RADIOTHERAPY TIMING IN 4820 PATIENTS WITH BREAST CAN- 

CER. THE UNIVERSITY OF FLORENCE EXPERIENCE 

L. Livi 1 

1 CAREGGI HOSPITAL, Firenze, Italy 

Purpose: The objective of this study was to analyze the relationship between 

delay in radiotherapy (RT) after breast conserving surgery and ipsilateral 

breast recurrence (BR). 

Materials: We included in our analysis 4,820 patients with breast cancer 

who underwent postoperative RT at the University of Florence. Patients were 

categorized in four groups according to time intervals (T1:180 days). 

Results: At the multivariate analysis, timing RT does not reach statistical significance 

in patients who received only postoperative RT (n:1,935) or RT and 

HT (n:1,684) or RT, CHT and HT (n:529). In the postoperative RT only group 

age at presentation, surgical margins and boost to the tumour bed resulted 

to be independent prognostic factors to BR. In the RT plus HT group, age 

at presentation and boost emerged as independent prognostic factors to BR 

(p=0.006 and p=0.049, respectively), while in the RT plus CHT and HT group 

only multifocality resulted to be an independent BR predictor ( p=0.01). Only 

in the group of patients treated with RT and CHT (n:672), multivariate analysis 

with stepwise selection showed timing as independent prognostic factor 

(HR:1.59, 95%CI:1.01-2.52; p=0.045). By analyzing this group of patients 

we found that mostly of patients included had worse prognostic factors and 

received CHT according CMF schedule before undergoing RT. 

Conclusions: Delay in the start of RT does not increase the risk of LR in 

patients irrespectively to the adjuvant treatment received. 

621 poster 

REMISSION RATES AFTER NEOADJUVANT RADIOCHEMOTHER- 

APY FOR LOCALLY ADVANCED BREAST CANCER 

S. Roth 1 , I. Lang 1 , B. Gerlach 2 

1 UNIVERSITAETSKLINIK, Radiotherapy, Duesseldorf, Germany 

2 STAEDTISCHE KRANKENANSTALTEN, Radiotherapy, Dortmund, Germany 

Purpose: Evaluation of remission rates after neoadjuvant chemotherapy followed 

by or combined simultaneously with preoperative external radiotherapy 

+/- HDR-interstitial implants. 

Materials: 149 women with biopsy-proven breast tumors were evaluated 

in this retrospective study. Of the 149 patients 45 received preoperative 

chemotherapy (4 x EC) and sequentially 50 Gy external radiotherapy. The 

residual were treated by 50 Gy external radiotherapy plus 10 Gy interstitial 

HDR-implants combined with simultaneous mitoxantrone. The stage distribution 

was in the external radiotherapy group: 2A n=12, 2B n=16, 3A n=7, 3B 

n=10 and more advanced in the external plus interstitial radiotherapy group: 

2A n=7, 2B n=38, 3A n=32, 3B n=27. 

Results: The pCR in the 45 pts. with external RT was 36% and the pCR 

in the external and interstitial group 31%. In the external group the pCR rate 

was in cT2 43% (9/21), in cT3 29% (4/14), in cT4 30% (3/10). In the combined 

external and interstitial RT-group the pCR- rate was in cT2 42% (8/19), in cT3 

43% (20/58) and in cT4 19% (5/27). 

Conclusions: The combination of neoadjuvant chemotherapy and preoperative 

radiotherapy results in a high pCR rates. If there is an impact on relapse 

free and overall survival should be assessed within the framework of a clinical 

trial.


622 poster 

RT BOOST VOLUME REDUCTION FOR BREAST CANCER PATIENTS 

USING HISTOPATHOLOGY DATA: INITIAL RESULTS 

J. Stroom 1 , A. Schlief 2 , H. Peterse 3 , H. Bartelink 1 , K. Gilhuijs 2 


2 NKI-AVL, Radiology, Amsterdam, Netherlands 

3 NKI-AVL, Pathology, Amsterdam, Netherlands 

Purpose: At the NKI-AvL, breast-conserving therapy (BCT) consists of limited 

surgery to remove the tumor bulk followed by total breast irradiation with 

an extra boost to the excision site. The boost target is the delineated excision 

site plus an isotropic CTV margin equal to 15 mm minus the minimum 

tumor-free distance between tumor bulk and edge of the surgical specimen. 

Although surgery aims to remove the tumor with symmetric margins, this is 

rarely accomplished. The aim of this study is to investigate potential reduction 

of the boost volumes without loss of tumor coverage when asymmetry of 

tumor excision is compensated by a reverse asymmetry during radiotherapy. 

Materials: Firstly, an extensive pathology tumor distribution study was performed 

to assess the frequency and extent of microscopic disease around the 

gross tumor in the breasts of 37 patients undergoing BCT. This resulted in a 

model of disease spread around the gross tumor, which allows us to calculate 

the probability of finding disease outside a specific volume (Pout,vol). Secondly, 

the model was prospectively applied to 10 BCT patients scheduled to 

receive post-operative radiotherapy. Using the relative position of the tumor 

bulk in the excision specimen, the model was used to calculate Pout,TTV, 

with TTV the total treated volume (TTV: surgery + CTVboost). We subsequently 

determined new, anisotropic CTV margins that minimized the CTV 

volume but maintained Pout,TTV (see Figure). Potential volume reductions 

of CTVboost and TTV were calculated. 

Results: We found that the microscopic disease is isotropically distributed 

around the gross tumor, and that there is 35% probability of finding disease 

beyond 15 mm from the gross tumor. For the 10 RT patients however, the average 

Pout,TTV was only 17%. This is due to the asymmetry during surgery, 

which yields total TTV margins that can in some directions be considerably 

larger than the intended 15 mm. By applying new asymmetric CTV margins 

that reverse the asymmetry during surgery while keeping Pout,TTV = 17%, 

the (isotropic) TTV margin becomes on average 20 mm. Nevertheless, the 

CTVboost and the TTV are on average reduced by 27% (= 19cc) and 20% (= 

53cc), respectively. 

Conclusions: Current volumes of the radiation boost field in the breast may 

be unnecessarily large due to the asymmetrically excised breast tumors. Correcting 

for this asymmetry may reduce the boost volume considerably, while 

maintaining tumor coverage. 

623 poster 

SUPRACLAVICULAR FOSSA AND AXILLARY LYMPH NODES IRRA- 

DIATION IN BREAST CANCER: IS THERE A BETTER TECHNIQUE? 

M. Ben-Dvaid 1 , V. Pytigorskaya 1 , Z. Symon 1 , R. Pfeffer 1 

1 SHEBA MEDICAL CENTER, Radiation Oncology, Ramat-Gan, Israel 

Purpose: Traditionally, supraclavicular fossa was treated to a distance of 3cm 

below the skin surface in normal weight and 5cm in obese women. The axilla 

was treated to mid point of the body, with two oblique opposing fields using 

6MV photons. The 100% dose was prescribed to the SCV point, and a posterior 

axillary field was added to complete 100% dose to the axillary point. Due 

to the deep position of the axillary point, higher doses were delivered to the 

soft tissue and skin at the anterior part the body through the posterior field, 

causing acute skin reaction with desquamation and pain, scar formation and 

worse cosmetic outcome. A dosimetry exercise is presented here; comparing 

this traditional radiation technique with combination of anterior electron 

field and posterior photon beam aiming to reduce the surface dose using 3D 

conformal radiation. 

Materials: Treatment plans of 10 women with node positive breast cancer 

who were treated at the Sheba Medical Center were analyzed. All women 

were simulated using CT scan, and a 3D treatment plan was generated. The 

SCV and axillary points were positioned as described above; ipsilateral lung 

was contoured on each CT slice. Treatment was delivered to the whole breast 

using 2 tangential fields, the axilla and the supraclavicular area with two opposed 

fields, using 6MV photons. All plans were prescribed to deliver 100% 

of the dose (50Gy) to the SCV point with additional axillary field to allow for 

100% dose delivered to the axillary point (plan #1). For each patient, two 

additional plans were generated: Plan #2: 15MeV AP and 6MV PA; Plan #3: 

15MeV AP and 15MV PA, with the same reference points as target. The Maximal 

V20 allowed for the ipsilateral lung was 30% in all plans. The plans were 

then compared regarding the coverage of the reference points and the DVH 

of normal structures (ipsilateral lung and 5mm anterior body skin area). 

Results: When comparing the mean dose to the anterior 5mm of the skin, 

there was a 20% reduction with plans 2 and 3 compared to plan 1, 89.9% 

and 90% vs. 114%, respectively (p=0.04). The V20 of the ipsilateral lung 

was below 30% in all plans, with 52% reduction of the V20 when using plans 

2 and 3 (p=0.04). The mean V20 was 25% with plan 1and 13% for plans 2 

and 3 (p=0.04). The mean dose to the SCV and axillary points were 120% 

and 101%, with plan 1 compared to 107% and 101% with plans 2 and 3, 

respectively (11% reduction) (p=0.05).

Conclusions: Using combination of anterior electron field with posterior 6MV 

or 15MV photons to treat the SCV and axillary region resulted in excellent 

target point’s coverage and reduced dose to normal tissue surrounding the 

target volume. 

624 poster 

TARGET VOLUME LOCALISATION FOR TUMOUR BED RADIOTHER- 

APY IN EARLY BREAST CANCER 

S. Guglani 1 , E. de Winton 2 , E. Vamvakas 3 , D. Willis 3 , K. Yuen 4 , B. Chua 

5 

1 

GLOUCESTERSHIRE ONCOLOGY CENTRE, Clinical Oncology, Cheltenham, 


2 

BRISTOL HAEMATOLOGY AND ONCOLOGY CENTRE, Clinical Oncology, 


3 

PETER MACCALLUM CANCER CENTRE, Radiation Therapy, Melbourne, 

Australia 

4 

PETER MACCALLUM CANCER CENTRE, Center for Biostatistics Clinical 

Trials, Melbourne, Australia 

5 

PETER MACCALLUM CANCER CENTRE, Radiation Oncology, Melbourne, 

Australia 

Purpose: This study compared clinical and CT techniques for target volume 

localisation of tumour bed boost in patients undergoing whole breast radiotherapy 

following conservative surgery for early breast cancer. 

Materials: Patients were prospectively recruited and CT scanned in the treatment 

position following clinical delineation and wiring of the whole breast, 

surgical scar and boost field as per protocol guidelines. CT boost volumes 

were contoured in 3 dimensions: The tumour bed (delineated by surgical 

clips and seroma cavity) was expanded by 1cm to the CTV and 2cm to PTV. 

A definitive treatment plan was generated to encompass the PTV with ≥90% 

isodose using electrons. A hypothetical plan was also generated to cover 

the clinically-determined boost field by the 50% isodose for comparison.The 

primary endpoint was the difference in PTV coverage by the 90% isodose between 

clinical and CT plans. PTV coverage using the clinical technique was 

considered insufficient if ≥10% less than PTV coverage using the CT technique. 

The hypothesis of >10% of cases in the population with insufficient 

PTV coverage from the clinical technique was tested using a one-sided test. 

The secondary endpoints included the difference in electron energy (EE) selected 

and the percentage volume difference of normal breast tissue covered 

by the 50% isodose comparing the two techniques. 

Results: Fifty patient plans were evaluated. The median PTV coverage 

by the 90% isodose using the clinical and CT techniques was 29% (range, 

5%90%) and 83% (range, 25%100%) respectively. Insufficient PTV coverage 

using the clinical technique was observed in 88% of patients (95% CI, 

77%95%; p < 0.0001).Clinical examination resulted in equivalent or underestimated 

EE compared to the CT technique in 30% and 70% of cases respectively. 

The median % volume of normal breast tissue encompassed within the 

50% isodose was 11% vs. 22% for clinical vs. CT technique respectively (p 

< 0.0001). The % volume of normal breast tissue within the 50% isodose of 

the CT boost was ≥10% more than that of the clinical boost in 54% of cases 

and


lack support and counseling to deal with. Half an hours meeting with the contact 

nurse before starting the radiation therapy does not leave much time to 

discuss topics like family, body image, changing of role in the family and job 

situation etc. 

Materials: A quantitative prospective controlled research based on questionnaires 

answered by 89 women 6 weeks after finishing the radiation therapy. 

90 women were included, with 30 women to each intervention A, B and C. Intervention 

A, control group representing the actual practice, offers the patient 

half an hour’s consultation on the first treatment day with the contact nurse. 

Intervention B, offers in addition to A also a planned half an hour consultation 

on one of the last treatment days. Intervention C offers the patients A and B 

and in addition to this half an hours consultation 10 and 30 days after having 

finished the radiation therapy. 

Results: When it comes to act of competence related to care of the skin all 

three interventions are relatively high indexed (72-79). This indicates that in 

relation to the physical area there is no benefit to offering consultation, as in 

intervention B and C. In areas like sexuality and spirituality, it is the same. 

Regarding fatigue it shows that the patients benefit significantly from nursing 

consultation 10 and 30 days after finishing radiation therapy. Regarding body 

image the results indicate that patients benefit from a nursing consultation 

one the last days of their treatment, and it does not improve further in intervention 

C. There is significantly difference when it comes to counseling and 

support in the mental area from A to B to C. This indicates that patients benefit 

from nursing consultation 10 and 30 days after finishing radiation therapy. 

In the area "role in the everyday life patients benefit from nursing consultation 

10 and 30 day after finishing the radiation therapy. Finally data show that 

from 73% to 100% of the women attach great importance that they met their 

contact nurse at the nursing consultation. 

Conclusions: This Study has provided evidence that nursing consultations 

with the contact nurse can be a valuable method to ensure that patients are 

given the possibility of individually counseling and an experience of support 

and continuity during and after radiation therapy. 

628 poster 

THREE-DIMENSIONAL CONFORMAL RADIATION THERAPY TO 

THE SUPRACLAVICULAR AND INFRACLAVICULAR NODES : 

COMPARISON WITH STANDARD TECHNIQUE 

N. Vasev 1 , O. Arsovski 2 , L. Dusko 3 

1 

RADIOTHERAPY AND ONCOLOGY, Department of breast cancer, Lodz, 

Poland 

2 

RADIOTHERAPY AND ONCOLOGY, Brachytherapy, Lodz, Poland 

3 

RADIOTHERAPY AND ONCOLOGY, Physics, Lodz, Poland 

Purpose: Irradiation of the supraclavicular (SCV) and infraclavicular (ICV) 

nodal groups is often indicated in the clinical radiotherapy of patients with 

breast cancer. We estimated the radiation dose received by these nodal 

groups in a series of patients treated with an optimized dosimetric technique 

and compared these doses to doses received with standard technique . 

Materials: Sixty four patients underwent 3D treatment planning. SCV and 

ICV nodal groups were outlined by using anatomic structures. Optimized 

dose calculations were then made for SCV and IFV and compared with standard 

dose calculations using the supraclavicular field and the depth of 3 cm. 

Results: Median maximum depth (MMD) of the SCLN nodes was 6,1 cm. 

MMD of the ICLN was 7.16. Volume of the SCLN encompassed with 90% 

surface isodose in the optimized conformal plans was 94.7% (range 89%- 

99.07), compared with a 74.39% (range 56.09-95.67%) in standard plans. 

Volume of the ICLN was 70.8% (53.4%-100%) in the optimized conformal 

plans, compared with 17.66% (7.7%-88.6%)in standard plans. Optimization 

for all conformal radiation therapy plans was made with 15 MeV photon energy. 

Conclusions: The irradiation of breast lymph nodes requires 3D conformal 

processing of the treatment. Differences in anatomical location and in 

depth of SCV and IFV nodes significantly affected the dose coverage of these 

nodes. Optimized treatment parameters should be selected to ensure adequate 

irradiation of target volumes while sparing healthy tissues as much as 

possible. Photon energy of 15 MeV could be optimal selection. 

629 poster 

TOLERANCE, SAFETY AND ACCEPTANCE RESULTS OF A PHASE 

I/II TRIAL OF ACCELERATED PARTIAL BREAST IRRADIATION 

USING PERMANENT BREAST 103PD SEED IMPLANT (PBSI) 

J. P. Pignol 1 , B. Keller 1 , E. Rakovitch 2 , R. Sankreacha 1 

1 

SUNNYBROOK HEALTH SCIENCES CENTRE, Medical Physics, Toronto, 

Canada 

2 

SUNNYBROOK HEALTH SCIENCES CENTRE, Radiation Oncology, Toronto, 

Canada 

Purpose: A permanent breast seed implant (PBSI) technique has been developed 

for patients eligible for Accelerated Partial Breast Irradiation (APBI). 

PBSI realizes the implantation of 103 Pd stranded seeds under ultra-sound 

guidance in a single one-hour session using light sedation and skin freezing. 

A Phase I/II clinical trial has been activated to assess the treatment tolerance, 

feasibility and efficacy of this novel treatment. 

Materials: Eligible patient includes those referred for adjuvant radiotherapy 

for an infiltrating ductal carcinoma T 3 cm in diameter, surgical margin ≥ 2 

mm, no extensive in situ carcinoma, no lympho-vascular invasion, and negative 

lymph nodes. Patients received a permanent seed implant and a minimal 

peripheral dose of 90Gy was prescribed to the CTV identified on the CT scan 

plus a margin of 1 to 1.5 cm 

Results: From May 2004 to March 2007, 122 patients were included in the 

study and 67 patients received PBSI. Fifty five patients were deemed technically 

challenging mainly because of a large seroma (19/55) or large PTV 

(16/55). The procedure was well tolerated, with 17% of the patients presenting 

a significant pain following the procedure. Only one patient (1.5%) presented 

an acute skin reaction Grade III from the NCI-CTC scale. The rates 

of acute moist desquamation, erythema and indurations were respectively 

10.4%, 42% and 27%. The rate of grade I telangiectasia was 14% at 1 years. 

The rate of skin reactions is dramatically reduced when the skin receives less 

than 85% of the prescribed dose. Using the RTOG questionnaire, 80 to 90% 

of the patients were very satisfied by their treatment and the remaining was 

satisfied by the treatment. One patient developed an abscess (1.5%) resolving 

after antibiotics. No patient has recurred after a median follow-up of 31 

months [range 11 to 49 months]. 

Conclusions: PBSI feasibility, safety and tolerance compares favorably with 

external beam and other partial breast irradiation techniques. This technique 

requires a careful patient selection. 

630 poster 

USE OF AXILLARY DEODORANT AND THE IMPACT ON ACUTE 

SKIN TOXICITY DURING RADIATION THERAPY FOR BREAST 

CANCER: A RANDOMIZED TRIAL 

V. Theberge 1 , A. Dagnault 1 , F. Harel 2 

1 

CHUQ-HOTEL-DIEU DE QUEBEC, Radiation Oncology, Quebec city, 

Canada 

2 

CHUQ-HOTEL-DIEU DE QUEBEC, Research center of Hotel-Dieu de 

Quebec, Universite Laval, Quebec city, Canada 

Purpose: The effect of using deodorant during irradiation for breast cancer 

was never specifically evaluated. The objective of this study was to determine 

prospectively the impact of deodorant use on acute skin toxicity and quality 

of life during radiation therapy (RT).

Materials: Eighty-four patients were randomized prior to RT for breast cancer 

to use deodorant everyday (DG, n=40) or not (NoDG, n=44). Antiperspirant 

with aluminium was not allowed. Patients were stratified according to axillary 

irradiation and previous chemotherapy. Patients with concomitant chemotherapy 

or partial breast irradiation were excluded. Patients were evaluated at 

the end of RT and two weeks post-RT for acute skin toxicity using the RTOG 

acute skin toxicity criteria. Toxicity evaluations were always performed by the 

principal investigator blinded to the group assignment. Symptoms of acute 

skin toxicity (discomfort, pain, pruritus, sweating) and quality of life (using the 

EORTC QLQ-C30 scale) were self-evaluated. For each toxicity criteria, the 

point estimate of rate difference (D) with 95% one-sided upper confidence 

limit (UCL) was computed. To claim noninferiority due to deodorant use, the 

only requirement is that the UCL is lower than the noninferiority margin fixed 

to 12,8% as suggested by Rhmel (2001). P value associated with the null 

hypothesis of inferiority was also computed. 

Results: Grade 2 axillary radiodermatitis occurred in 9/40 (23%) in DG vs 

13/44 (30%) in NoDG (D=-7%; UCL=8.6%), satisfying statistical criteria for 

noninferiority (p=0.0189). Grade 2 breast radiodermatitis occurred in 30% 

in DG vs 34.1% in NoDG (D=-4.1%; UCL=12.7%), also satisfying statistical 

criteria for noninferiority (p=0.0489). Similar results were observed for the 

self-reported evaluations (discomfort, pain and pruritus). Both groups showed 

similar quality of life. Furthermore, less sweating was reported by patients of 

the DG (18% vs 39%, p=0,0322). 

Conclusions: According to our definition of noninferiority margin, occurrence 

of skin toxicity was statistically equivalent in both groups. Using deodorant 

(not antiperspirant with aluminium) during RT for breast cancer does not increase 

skin toxicity and its related symptoms. As expected, sweating decreased 

significantly with the use of deodorant. There is no evidence to forbid 

deodorant during radiotherapy for breast cancer. 

631 poster 

VASCULAR ENDOTHELIAL GROWTH FACTOR C SERUM LEVELS 

IN PATIENTS WITH BREAST CANCER 

I. Gisterek 1 , R. Matkowski 1 , P. Sedlaczek 2 , K. Szewczyk 1 , U. Staszek 1 , 

P. Biecek 3 , A. Lacko 1 , M. Bebenek 4 , M. Pudelko 4 , J. Kornafel 1 

1 

WROCLAW MEDICAL UNIVERSITY, Oncology, Wroclaw, Poland 

2 

WROCLAW MEDICAL UNIVERSITY, Department of Clinical Immunology, 

Wroclaw, Poland 

3 

WROCLAW UNIVERSITY OF TECHNOLOGY, Department of Mathematics 

and Computer Science, Wroclaw, Poland 

4 

LOWER SILESIAN ONCOLOGY CENTER, Surgery, Wroclaw, Poland 

Purpose: Vascular endothelial growth factor C (VEGF-C), a member of 

VEGF family binds to vascular endothelial growth factor receptor-3 on lymphatic 

endothelial cells and promotes lymphangiogenesis. It plays a critical 

role in the progression of malignant tumors. Since determining of blood 

biomarkers is minimally invasive and relatively easy to perform procedure and 

there are several reports suggesting that soluble VEGF-C might be potential 

marker of poor prognosis and lymph node metastases, we analysed the 

serum VEGF-C levels in human breast cancer in relation to clinicopathologic 

parameters and treatment outcome. 

Materials: Serum VEGF C levels were measured preoperatively in 349 patients 

with breast cancer using immunohistochemical method (ELISA) with 

R&D Systems Kit (Wiesbaden, Germany). All patients presented with operable 

disease (stage I: n=153, 43,84%; stage II: n=101, 28,94%, stage III: n=83; 

23,78%) and underwent primary surgery. All patients received standard adjuvant 

treatment. Ductal carcinoma was diagnosed in 228 patients, lobular in 

65, other types of invasive carcinoma in 44 and ductal carcinoma in situ in 12 

women. The median age of patients was 58 years (range: 29-83). 

Results: The median serum VEGF-C levels was 3098 pg/ml, mean 3040 

pg/ml (range 1068 - 5234 pg/ml). There was no significant correlation between 

serum VEGF-C levels and clinicopathologic parameters (pathological 

stage, tumour size and grade, axillary lymph node status, HER2, estrogen 

receptor alpha and progesterone receptor expressions, patients age, overall 

and disease free survival). We observed statistically significant correlation 

between VEGF-C levels and erythrocytes counts (p=0.0368), leukocytes 

counts (p=0.043) and platelets counts (p=0.0000273). 

Conclusions: Circulating serum VEGF C levels does not display prognostic 

value in breast cancer patients. It does not correlate with survival or any of 

important clinicopathological features. We found correlation between blood 

cell counts and serum VEGF-C levels. The mechanism of this relationship is 

not fully defined however it does not seem to have any clinical significance. 

CLINICAL/DISEASE SITES : CNS 

Clinical/Disease sites : CNS 

632 poster 

S 207 

3D-CONFORMAL RADIATION THERAPY (CRT) PLUS STEREOTAC- 

TIC BOOST (SRT) AND CONCOMITANT TEMOZOLOMIDE IN HIGH 

GRADE GLIOMAS (HGG): FINAL REPORT 

G. Apicella 1 , M. Balducci 1 , C. Anile 2 , S. Manfrida 1 , N. Dinapoli 1 , G. R. 

D’Agostino 1 , L. Azario 3 , G. Mantini 1 , V. Frascino 1 , A. Fiorentino 1 , A. 

Mangiola 2 , V. Valentini 1 

1 POLICL. UNIV. "A. GEMELLI", Radiation Oncology, Roma, Italy 

2 POLICL. UNIV. "A. GEMELLI", Institute of Neurosurgery, Roma, Italy 

3 POLICL. UNIV. "A. GEMELLI", Department of Physics, Roma, Italy 

Purpose: We analyzed impact on survival of a concomitant and/or sequential 

conformal stereotactic boost for patients with HGG. 

Materials: Eligible criteria were: age over 18 yrs-old, histological diagnosis of 

HGG, KPS > 70, pre and post-surgical MRI evaluation, consent form. Primary 

end-point was survival; secondary end-points were: local control and toxicity. 

The accrual number to increase survival of 25% related to Stupp’s study, was 

extimated of 35 pts, according to the Simon mode. RTOG score was used 

to grade toxicities. Dose to CTV1 (ring enhancement plus residual tumor if 

present) was 6940 cGy, to CTV2 (CTV1 plus a 1,5 cm margin) was 5040 

cGy in concomitant plus sequential SRT group (A) and 5940 cGy in only 

sequential SRT group (B) ; dose to CTV3 (CTV1 plus oedema) was 3960 cGy. 

Concomitant SRT boost was delivered at the dose of 90 cGy three times a 

week during weeks 3 to 6 while a sequential SRT boost was administered in 

four fractions of 250 cGy each. TMZ (75 mg/m2 ) was administrated during 

the first two weeks of radiotherapy for group A and for 4 weeks for group B. 

Adjuvant TMZ (150-200 mg/m2 ) was administered for at least 6 cycles. 

Results: From November 2003 to February 2008 41 pts affected by HGG 

were enrolled. Median age was 50 yrs-old (range 25-65); histological subtypes 

were: 36 (88%) glioblastoma multiforme (GBM) and 5 (12%) anaplastic 

astrocitoma; 28 pts (68%) presented a macroscopic residual tumor while13 

pts (12%) had no visible tumor in the postsurgical scan. RPA (Recursive 

Partitioning Analysis) classes were: 7 pts class I , 10 class III, 23 class IV, 

one patient class V. Complete or partial response after radiotherapy was observed 

in 27 pts (64%); stable disease in 11 (28%) and progression in 3 (8%). 

Neurological acute toxicity G1-2 was 2% (5/41) and G3 was observed in 1/41 

pts; late toxicity in terms of radionecrosis was observed at 14 mts in only one 

case. At a median follow-up of 43 mts (range 6-53) 22 pts (54%) are alive and 

19 (46%) are dead. Median overall survival was 33 mts and actuarial 2 yrs 

survival is 61%. Median progression free survival (PFS) was 23 mts: PFS at 

2 yrs was 33%. Among GBM median survival was 31 mts (55% at two year). 

We observed a statistically significative difference (p=0.03) between R0 and 

R1 patients, but no difference between the two schedules (0,145). 

Conclusions: Stereotactic boost in TMZ schedule seems to increase survival 

in HGG with acceptable toxicity. 

633 poster 

A REVIEW OF THE INCIDENCE AND RADIOLOGICAL FEATURES 

OF PSEUDO-PROGRESSION IN A COHORT OF GLIOBLASTOMA 

PATIENTS TREATED WITH TEMOZOLOMIDE AND CHEMO- 

RADIATION 

S. Jefferies 1 , C. Magri 1 , D. Scoffings 2 , N. Antoun 2 , K. Burton 1 , L. Muffett 

1 , P. Jones 3 , R. Jena 1 , N. Burnet 4 

1 

ADDENBROOKE’S HOSPITAL, Oncology, Cambridge, United Kingdom 

2 

ADDENBROOKE’S HOSPITAL, Radiology, Cambridge, United Kingdom 

3 

UNIVERSITY OF CAMBRIDGE, HUTCHISON/MRC, Oncology, Cambridge, 


4 

UNIVERSITY OF CAMBRIDGE, ADDENBROOKE’S HOSPITAL, Oncology, 


Purpose: Radiotherapy (RT) and concomitant plus adjuvant temozolomide 

(TMZ) is the new standard of care for glioblastoma (GBM). Interpretation of 

imaging after radiotherapy needs to be undertaken with caution due to the 

reported occurrence of pseudo-progression (PP). The aim of this study was 

to retrospectively assess the incidence and radiological features of PP in a 

cohort of patients treated with TMZ-RT. 

Materials: The pre- and post-radiotherapy MRI brain scans were collected 

for all patients treated with TMZ-RT for GBM at Addenbrooke’s Hospital between 

April 2005 and July 2007. Radiotherapy consisted of 60Gy in 6 weeks 

combined with daily TMZ (75mg/m2 /day). Adjuvant TMZ commenced at 4 

weeks after RT for 6 cycles (150-200mg/m2/1-5 days/every 4 weeks). MRI’s 

were obtained pre-RT, at 4 weeks after RT and 4 and 7 months. All images 

were anonymised and reviewed without clinical details by the same radiologist. 

The images were assessed for progression according to the radiologists’ 

standard reporting criteria and MacDonald’s Criteria. Images were scored for 

presence of necrosis, enhancement (margin, solid), non-contrast enhancing 

tumour, oedema, cyst(s), multifocality, tumour or oedema crossing midline 

and subependymal spread 

Results: Of all patients treated, 16 had completed TMZ-RT and adjuvant 

TMZ and were eligible for this review. Six patients had no evidence of pro-

S 208 CLINICAL/DISEASE SITES : CNS 

gression on MRI at 1, 4, 7 months. Using MacDonald’s criteria 10/16 patients 

were found to have evidence of suggestive radiological progression. Of the 10 

with worsened radiology 4 (40%) resulted from PP with evidence of increase 

in size of tumour on MRI at 1 month (1), 1 and 4 months (2) or 4 months 

(1) with subsequent improvement of MRI scans. Two patients progressed 

on MRI at 1, 4 and 7 months. 4/16 patients progressed at 4 (1) and 7 (3) 

months. Four out of 16 patients (25%) demonstrated PP using Macdonald’s 

criteria. The PP incidence was the same with standard radiological reporting. 

No imaging features correlated with PP versus true progression. 

Conclusions: Radiological PP occurred in 25% of GBM patients treated with 

chemo-irradiation with TMZ and occurred at 1 and 4 months. It was detected 

by both MacDonald’s Criteria and standard reporting criteria. No specific 

radiological features could be identified that detected PP versus true progression. 

Further imaging modalities need to be assessed to see if these can 

distinguish for PP. These data support the notion to continue TMZ in case of 

progressive lesions at 1 and 4 months after RT/TMZ. 

634 poster 

AN OUTCOME REVIEW OF THE INTRODUCTION OF CONCOMI- 

TANT AND ADJUVANT TEMOZOLAMIDE WITH RADIOTHERAPY 

FOR GLIOBLASTOMA MULTIFORME IN A UK CENTRE. 

B. J. Haylock 1 , F. Alam 2 , A. Zia 1 , H. Wong 2 

1 

CLATTERBRIDGE CENTRE FOR ONCOLOGY, Clinical Oncology, Bebington, 

Merseyside, United Kingdom 

2 

CLATTERBRIDGE CENTRE FOR ONCOLOGY, Radiation Oncology, Bebing- 

ton, Merseyside, United Kingdom 

Purpose: The prognosis for glioblastoma multiforme (GBM) is very poor. 

Radical radiotherapy is considered the mainstay of treatment following 

surgery. The role of chemotherapy has been controversial until the publication 

of a landmark phase III randomised controlled trial of concomitant and 

adjuvant Temozolomide(TMZ) and radiotherapy (Stupp et al) in abstract form 

at ASCO 2004. On the basis of this study TMZ was incorporated into our 

standard treatment protocol. We describe the results of a clinical audit undertaken 

to validate this change in practice. 

Materials: All patients were referred via the Walton Centre for Neurology 

and Neurosurgery, following biopsy and debulking surgery if possible to the 

Clatterbridge Centre for Oncology. Eligible patients were: histologically confirmed 

WHO grade IV glioma (GBM); age between 18 years and 70 years; 

WHO performance status (PS) 0,1 or 2, and treated with the Stupp regime 

(i.e. Radical radiotherapy - 60 Gy in 30 daily fractions with concomitant TMZ 

75mg/m2 daily 7days/week) followed by up to 6 cycles of adjuvant TMZ (150- 

200mg/m2). A retrospective analysis was performed for overall and progression 

free survival as well as prognostic variables, compliance, toxicity and 

cost. 

Results: One hundred and nine eligible patients, 39 females and 70 males, 

were referred between June 2004 and June 2007. The median age was 52.79 

(range18-68) years. The majority of patients were PS 0 or 1 (84%), and had 

undergone macroscopic debulking (72 %). With a median followup for surviving 

patients of 13.4 months the median survival was 12 months (95% CI 

10.6 13.4) and the 2 year survival was 15 % see Fig 1. The median progression 

free survival was 10 months (95% CI 8.7 11.3). The median survival 

a similar group of patients treated without TMZ was 8.5 months. Favourable 

prognostic variables included PS and extent of surgery but not age (< or > 

60 years). Only 47.7% patients achieved full drug compliance. The commonest 

reason for stopping was disease progression or death. The commonest 

medical complication was thrombocytopenia. The real cost of adding TMZ is 

discussed. 

Conclusions: The results of this review of treating a real UK population in the 

NHS with a trial regime of concurrent and adjuvant TMZ has shown a benefit 

over the previous standard treatment. An analysis of prognostic factors, 

the real drug costs and the treatment of recurrence following relapse will be 

discussed. 

635 poster 

ANALYSIS OF PRE-OPERATIVE VERSUS POST-OPERATIVE MAG- 

NETIC RESONANCE IMAGING (MR) IN RADIOTHERAPY PLANNING 

FOR GLIOBLASTOMA MULTIFORME (GBM) 

C. Deville 1 , D. McMichael 1 , S. Both 1 

1 UNIVERSITY OF PENNSYLVANIA, Radiation Oncology, Philadelphia PA, 

USA 

Purpose: The modest benefit of adjuvant radiotherapy in resected GBM is 

well-established. Utilization of MR fusion in treatment planning has facilitated 

tumor localization. Guidelines in clinical and gross tumor volume (CTV, 

GTV) delineation applying standard margins to enhancing tumor and peritumoral 

edema have been adopted. It is unclear whether immediate pre- or 

post-operative imaging is more appropriate for target delineation, specifically 

which presents a more favorable risk to benefit ratio in considering patterns 

of relapse versus sparing of critical structures. This study was undertaken to 

evaluate the differences in target volume definition based on immediate pre- 

and post-operative MRs and its impact on dosimetric coverage. 

Materials: Eleven patients with GBM undergoing adjuvant radiotherapy at our 

institution following maximum safe resection with pre- and post-operative MRs 

were retrospectively planned with IMRT or 3DCRT techniques. The CTV was 

defined as the area of enhancing tumor, edema, and a 2 cm margin on FLAIR 

sequences, while the GTV was defined as the area of enhancing tumor plus a 

2 cm margin on T1 post gadolinium contrast sequences. Two separate CTVs 

and GTVs were delineated for each patient using pre- vs. post-operative 

imaging fused to the planning CT data set. The CTV was treated to 51 Gy 

and GTV to 60 Gy with concomitant boost IMRT, or to 46 Gy with sequential 

GTV conedown to 60 Gy using 3DCRT based on departmental protocol with 

standard dose limits to organs at risk (brainstem, optic chiasm, optic nerves, 

and cochlea). Differences in size of pre- and post-operative MR defined targets 

were analyzed. The targets coverage evaluation was performed using 

the original plan employed for patient treatment (OPT). 

Results: Overall target volume varied with both pre- and post-operative MRs 

utilized in treatment planning without a consistent trend in size variation. If the 

pre-operative MR was used for the OPT, 95% of the post-operative defined 

CTV received a 100% of the prescribed dose (PD) while the GTV received 

between 88 and 100% of the PD. When the post-operative MR was used for 

the OPD, 95% of the pre-operative defined CTV received between 79 and 

98% of the PD, while the GTV received between 86 and 99% of the PD. The 

CTV coverage was adequate in 84% of the cases while the GTV coverage 

only in 26% of the cases. DVH indicators for all critical structures were within 

the limits. 

Conclusions: Neither pre- nor post-operative MR imaging consistently reduced 

target volumes. The use of pre-operative MR for target delineation 

seems to provide more adequate coverage at the CTV level as compared to 

post-operative MR target delineation. GTV coverage is comparable regardless 

of data set used, however not consistently adequate. Correlation among 

target definition, dosimetry and disease progression on surveillance MR may 

elucidate optimal study selection in initial treatment planning. 

636 poster 

ASSESSMENT OF VARIOUS STRATEGIES FOR 18F-FET PET- 

BASED DELINEATION OF TARGET VOLUMES IN HIGH-GRADE 

GLIOMA PATIENTS 

H. Vees 1 , S. Senthamizhchelvan 2 , O. Ratib 2 , R. Miralbell 1 , D. Weber 1 , 

H. Zaidi 2 

1 HUG, Radiation Oncology, Geneva, Switzerland 

2 HUG, Nuclear Medicine, Geneva, Switzerland 

Purpose: To assess the value and impact of 18F-fluoro-ethyl-tyrosine (18F- 

FET) positron emission tomography (PET) in clinical management and delineation 

of gross tumor volume (GTV) in patients with high grade gliomas as 

compared with MRI alone. In this study, seven methods for tumor delineation 

on 18F-FET-PET are compared with MRI-based delineation. 

Materials: The study population consisted of eighteen patients with high 

grade gliomas (grade III, 4 patients and IV, 14 patients). Listmode PET 

data acquisition (30 min) started immediately following injection of 200 MBq 

of 18F-FET. Seven image segmentation techniques were used to delineate 

18F-FET PET GTVs and the results compared to the manual MRI-derived 

GTV (GTVMRI). PET image segmentation techniques included manual delineation 

of contours (GTVman), an isocontour of a standardized uptake value 

(SUV) of 2.5 (GTV2.5), a fixed threshold of 40% and 50% of the maximum 

signal intensity (GTV40% and GTV50%), signal-to-background ratio (SBR)based 

adaptive thresholding (GTVSBR), gradient find (GTVGF), and region 

growing (GTVRG) algorithms. 

Results: Overall, molecular PET/CT imaging altered further management 

of most patients. Contours defined using GTVSUV failed to provide successful 

delineation in 75% of cases. In addition, the volumes and shapes 

of GTVs delineated using the other techniques were greatly affected by the 

selection of the segmentation algorithm. Overall, all GTVs defined on PETbased 

techniques were smaller than GTVMRI. Yet, PET often detected tumors 

that are not visible on MRI and added significant tumor extension outside 

the GTVMRI. 

Conclusions: 18F-FET PET/CT had a major impact on further clinical management 

of patients with high grade gliomas. The choice of the most appropriate 

18F-FET PET-based segmentation algorithm is crucial since it impacts 

both the volume and shape of the ensuing GTV. With adequate delineation, 

PET may add considerably to conventional MRI-guided GTV delineation.

637 poster 

ASSOCIATION OF 11C-METHIONINE PET UPTAKE WITH SITE OF 

FAILURE AFTER CONCURRENT TEMOZOLOMIDE AND RADIATION 

FOR GLIOBLASTOMA MULTIFORME 

C. Tsien 1 , I. Lee 1 , J. Larry 2 , T. Lawrence 1 , D. Gomez-Hassan 3 , R. Ten 

Haken 1 , L. Rogers 2 , Y. Cao 1 , M. Piert 4 

1 


2 

UNIVERSITY OF MICHIGAN, Neuro-Oncology, Ann Arbor MI, USA 

3 

UNIVERSITY OF MICHIGAN, Department of Neuro-Radiology, Ann Arbor 

MI, USA 

4 

UNIVERSITY OF MICHIGAN, Nuclear Medicine, Ann Arbor MI, USA 

Purpose: To determine if increased uptake on 11C-methionine-PET (MET- 

PET) imaging obtained prior to radiation therapy and temozolomide is associated 

with the site of subsequent failure in newly diagnosed glioblastoma 

multiforme (GBM). 

Materials: Patients with primary GBM were treated on a prospective trial 

with dose escalated radiation and concurrent temozolomide. As part of the 

study, MET-PET was obtained prior to treatment but was not used for target 

volume definition. Using automated image registration, we assessed whether 

the area of increased MET-PET activity (PET-GTV) was fully encompassed 

within the high-dose region and compared the patterns of failure for those 

with and without adequate high-dose coverage of the PET-GTV. 

Results: Twenty-six patients were evaluated with a median follow-up of 15 

months. Nineteen of 26 had appreciable (> 1 cm3) volumes of increased 

MET-PET activity prior to treatment. Five of nineteen patients had PET-GTV 

that was not fully encompassed within the high-dose region, and all five patients 

had non-central failures. Among the 14 patients with adequately covered 

PET-GTV, only 2 had non-central treatment failures. Three of 14 patients 

had no evidence of recurrence with over 1 year after radiation therapy. Inadequate 

PET-GTV coverage was associated with increased risk of noncentral 

failures. (p < 0.01). 

Conclusions: Pretreatment MET-PET appears to identify areas at highest 

risk for recurrence for patients with GBM. It would be reasonable to test a 

strategy of incorporating MET-PET into radiation treatment planning, particularly 

for identifying areas for conformal boost. 

638 poster 

CONFORMAL CNS IRRADIATION IN THE SUPINE POSITION IN 

CHILDREN. 

S. Pysklak 1 , E. Korab-Chranowska 1 , A. Chmiel 1 , K. Czaja 1 

1 UCHC, Radiotherapy, Cracow, Poland 

Purpose: Radiotherapy in children with diagnosed medulloblastoma requires 

prone positioning of the patient. However, there are certain circumstances 

(e.g. anesthesia, breath difficulties) when the prone position isn’t possible. 

A case of a patient with medulloblastoma, who underwent irradiation in the 

supine position, is described below. 

Materials: The patient was immobilized in the supine position using a custom 

head cushion and thermoplastic mask for the head and shoulders. CT scans 

were taken and sent to the 3D treatment planning system where the target 

volume and critical organs were outlined. The PTV was covered by two opposed 

cranial and two posterior spinal fields using 6MV photon beams. The 

facial skeleton was shielded by individual blocks and the collimator was rotated 

in order to match the inferior limits of the brain fields with the divergent 

superior border of the upper spinal field. The upper spinal field was symmetrical. 

The lower field was a half beam. The couch column and gantry were 

rotated so that the borders of the adjacent spinal fields were parallel. The 

spinal fields’ isocenters were at fixed longitudinal distances from the cranial 

isocenter. Also, DRRs of two simulation anterior fields (opposing beams to 

the spinal fields with the same isocenter) were generated in order to mark 

the shape of those fields on the patient’s mask and skin. The positions of 

the isocenters were marked on the mask and tattooed on the patient’s skin 

for the cranial and spinal fields, respectively. Also, SSD for each simulation 

spinal field and the gap between them was measured and verified with the 

treatment protocol. After 7th and 14th fractions (of 21) re-simulation was performed 

i.e. field jaws were repositioned asymmetrically in order to shift the 

gaps between the therapeutic beams. After a dose of 3507 cGy, the cranial 

area was boosted with two opposed photon fields, up to a total dose of 

5500cGy. 

Results: The treatment plan was verified with the PVI. Portal images of the 

treatment fields were taken during the 1st, 8th, and 15th fractions. Fusion 

of DRRs from the treatment planning system, simulation images and portal 

images indicated very good accuracy and reproducibility of patient positioning 

and realization of the plan. In vivo dosimetry with the MOSFET detectors was 

performed in order to check the dose delivered to the patient. 

Conclusions: A safe and accurate method of craniospinal irradiation in children 

with medulloblastoma in the supine position is presented. 

639 poster 


S 209 

FEASIBILITY STUDY OF AN INNOVATIVE IR-192 HDR PERI- 

OPERATIVE BRACHYTHERAPY TREATMENT IN FOCAL RECUR- 

RENT MALIGNANT GLIOMA 

M. G. Fabrini 1 , F. Pasqualetti 1 , R. Vannozzi 2 , F. Perrone 1 , V. Scotti 1 , S. 

Crespi 1 , L. Cionini 1 

1 S.CHIARA HOSPITAL, Radiotherapy and Oncology , Pisa, Italy 

2 S.CHIARA HOSPITAL, Neurosurgery, Pisa, Italy 

Purpose: The aim of this work is to present the first results of an original HDR 

brachytherapy technique for patients with unifocal recurrent gliomas o metastasis 

after primary treatment with surgery and radiotherapy +/- chemotherapy. 

We have use a balloon shaped inflatable applicator for HDR brachytherapy of 

two different diameters, which is surgically placed in the tumour resection 

cavity. 

Materials: Patients with focal recurrent unilateral, histological confirmed 

GBM or metastasis, after surgery, standard radiotherapy +/- chemotherapy, 

were considered eligible. All patients were clinical symptomatic for recurrence. 

From January 2005, 21 patients (19 recurrent GBM and 2 metastasis) 

14 male and 7 females, with an average age of 70 years and with KPS >70, 

has been treated with surgery and brachytherapy. This technique is based 

on the use of a balloon-shaped applicator to administer a single fraction of 

18 Gy to the target volume after surgical session. After the removal of the 

recurrence, the surgeon places, in the tumour resection cavity, the applicator 

and filled it by isotonic solution (12-16 cc) under microscopy guide, in order 

to adapt the balloon to the cavity. The source transit channel and the filler 

channel of the applicator remain outside the head as pass through a hole in 

the cranial bone patch. Therefore, the patient is awaked and undergoes to 

a Computed Tomography study in order to reconstruct the radioactive source 

channel and the balloon and to determine the dosimetric plan. Afterwards, 

the BT is performed by means of an HDR, computer controlled, Ir-192 source 

(Nucletron, Holland), and the sources positions and their relative permanence 

times are optimised in order to fit the isodoses to the cavity shape. At the end 

of the BT, the applicator is removed in the neurosurgery room. After 20 days 

the patients are examined. In patients with KPS>70 a second line chemotherapy 

with Fotemustine is administered. Follow-up is performed with CT or RM 

every 3 months 

Results: Acute side effects of BT were mild nausea and headache, the 

complication rates were 4% (venous haemorrhage, 1/21pz). No incidence 

of wound infection or meningitis was observed. At the first control 16 patients 

(80%) have an improvement of the performance status with a relieve 

of the clinical sign. The median overall survival in patients with GBM was 25 

months, the median survival after brachytherapy was 8.4 months. 

Conclusions: Although our experience is at the beginning, interstitial HDR 

brachytherapy is well tolerated with acceptable toxicity and tumour growth 

control. Based on our experiences this procedure can be performed safely 

without excessive restriction. 

640 poster 

FOLLOW-UP STUDY OF PATIENTS WITH A NEW DIAGNOSIS OF 

GLIOBLASTOMA MULTIFORME TREATED WITH TEMOZOLOMIDE 

AND THALIDOMIDE 

A. Gramaglia 1 , E. Novelli 2 , A. Ravasio 1 , S. Nava 1 , F. Mattana 1 , M. 

Mapelli 1 , C. Bassetti 1 , V. Cerreta 1 

1 

POLICLINICO DI MONZA, Department of Radiation Oncology and Medical 

Physics, Monza, Italy 

2 

GRUPPO POLICLINICO DI MONZA, Department of Biostatistics, Novara, 

Italy 

Purpose: The chemotherapic agent temozolomide and the antiangiogenetic 

agent thalidomide have both demonstrated antitumor effects in patients with 

glioblastoma multiforme (GBM). The objective of the study was to determine 

if the combined strategy of temozolomide and thalidomide with radiotherapy 

is associated with an improved median survival. The efficacy and tolerability 

of temozolomide alone and in combination with thalidomide were explored in 

a single-institution 13 years experience. 

Materials: From April 1993 to May 2006, one hundred and seventy patients 

with GBM underwent microsurgical tumor extirpation and radioterapy: 82 

(48.2%) patients received no additional treatment (C), in 42 (24.7%) patients 

temozolomide was given alone (T) and 46 (27.1%) patients had a combined 

chemotherapy of temozolomide and thalidomide (TT). Radiotherapy parameters 

were a dose of 45 Gy delivered in 2.5-3 Gy fractions over 3-4 weeks, 

followed by a boost dose of 20 Gy delivered in 4-5 Gy fractions in 1 week. 

Temozolamide was administered starting at the end of radiotherapy with a 

dose of 200 mg/m 2 daily for 5 days, every 4 weeks. Thalidomide was started 

at the end of radiotherapy with a dose of 20 mg and escalated by 20 mg every 

week depending on patient tolerance, to a maximum of 100 mg daily. 

Results: Median survival, starting from the first radiotherapy, was 54 weeks 

(95% CI, 50-58 weeks) in C-patients, 83 weeks (95% CI, 36-130 weeks) in 

T-patients and 86 weeks (95% CI, 65-106 weeks) in TT-patients. Compared 

to the C-patients, the median survival of those who received temozolomide 

alone or in combination with thalidomide was 86 weeks (95% CI, 70-102


weeks), with a significant improvement in survival outcome (log-rank=6.613, 

p=0.010) (Figure 1). Temozolamide and thalidomide were well tolerated and 

only mild to moderate toxicities were observed. 

Conclusions: The strategy of combining temozolomide, thalidomide and radiotherapy 

in the treatment of GBM appears to be well tolerated and with 

favourable survival outcome. The addition of thalidomide in association 

with temozolamide does not offer a significant advantage over temozolamide 

alone. 

641 poster 

GLIOSARCOMAS: ANALYSIS OF 9 CASES TREATED WITH RADIO- 

THERAPY 

C. Edincik 1 , S. Sarihan 1 , S. Yildirim 1 , M. Kurt 1 , S. Cetintas 1 , S. Dogan 

2 , S. Tolunay 3 

1 

ULUDAG UNIVERSITY, FACULTY OF MEDICINE, Radiation Oncology, Bursa, 

Turkey 

2 

ULUDAG UNIVERSITY, FACULTY OF MEDICINE, Neurosurgery, Bursa, 

Turkey 

3 

ULUDAG UNIVERSITY, FACULTY OF MEDICINE, Pathology, Bursa, Turkey 

Purpose: Gliosarcoma account for 2-8% of all glioblastoma multiforme 

(GBM), depending on definitions used. They are primary brain tumors with 

mixed glial and mesenchymal components. Gliosarcomas usually affects 

patients in the sixth to seventh decade of life with a male preponderance. 

Treatment includes tumor resection, postoperative radiation therapy (RT) and 

sometimes chemotherapy. The goal of this study was to examine clinical features, 

treatment, survival and patterns of failure of gliosarcoma patients (pts). 

Materials: Between January 1996 and January 2007, 200 pts with GBM underwent 

RT at our hospital among them 9 gliosarcomas (4.5%). Surgical 

resection was total in 2, subtotal in 6 pts and 1 patient had steriotactic biopsy. 

All pts underwent tumor resection followed by postoperative RT. One patient 

received whole brain RT (30 Gy) and 8 underwent local RT with LINAC extended 

2.5 cm beyond to the edema margins. Total dose of RT was 60 Gy 

(range; 60-66 Gy) for 8 pts. Chemotherapy was administered to 2 pts after 

RT. 

Results: Two pts were male, 7 female, with a median age of 45 years (range; 

32-75 years). The median Karnofsky Performance Status was 80 (range; 50- 

90). The locations, all supratentorial, included temporal in 1, parietal in 1, 

frontal in 3 pts, and extensive in 4 pts. The median tumor size was 5 cm 

(range; 3-10 cm). Histologically, 3 pts consisted of sarcomatous component. 

At a median follow-up 8 months, 1-year survival was 33%. The median overall 

survival was 8 months (range; 3-14 months). All but one pts had local tumor 

recurrences during the follow-up time and 1 pt had lung metastasis at 4th 

months after diagnosis. Eight pts died of disease during the follow-up time. 

One patient was alive with evidence of residual tumor at evaluation time (12 

months). When the effect of various parameters on survival was evaluated; 

the presence of seizure was found to be as favorable prognostic factor (14 vs. 

5 months; p=0.036). 

Conclusions: Gliosarcomas are rare biphasic neoplasms of the central nervous 

system composed of a GBM admixed with a sarcomatous component. 

Despite prognosis of gliosarcomas remains poor, a multidisciplinary approach 

(surgery, RT and chemotherapy) seems to be associated with slight more prolonged 

survival times. 

642 poster 

HAVE CHANGES IN SYSTEMIC TREATMENT IMPROVED SURVIVAL 

IN PATIENTS WITH BREAST CANCER METASTATIC TO THE BRAIN? 

A. Dalhaug 1 , K. Marienhagen 2 , J. Norum 2 , C. Nieder 1 

1 NORDLANDSSYKEHUSET HF, Oncology, Bodoe, Norway 

2 UNIVERSITY OF NORTH-NORWAY, Oncology, Tromsø, Norway 

Purpose: Newly developed systemic treatment regimens might lead to improved 

survival also in the subgroup of breast cancer patients that harbour 

brain metastases. In order to examine this hypothesis, a matched pairs analysis 

was performed that involved one group of patients, which were treated 

after these new drugs were introduced (taxanes, trastuzumab, capecitabine 

etc.; treatment period 2001-2007), and one group of patients, which were 

treated approximately 10 years earlier. 

Materials: The contemporary group included all patients with brain metastases 

from breast cancer, which received whole-brain radiotherapy (WBRT) 

with 10 fractions of 3 Gy between 2000 and 2007 at the University Hospital 

of North-Norway. The patients (n=32) were identified from the database of 

the Radiation Oncology facility. No patients with carcinomatous meningitis 

were included. A historical control group treated with the same WBRT regimen 

was generated. From this larger group (n=47), 32 patients were selected 

for a matched pairs analysis without survival information available at the time 

of matching. To obtain two groups with comparable baseline characteristics, 

two matching criteria were used: prognostic class according to the published 

recursive partitioning analysis (RPA class) and use of additional local treatment 

for relapses after WBRT, e.g., radiosurgery or surgical resection. The 

Kaplan-Meier method was used to generate actuarial survival curves. These 

were compared with the log rank test. Wilcoxon- and Kruskal-Wallis-tests 

were used to compare the baseline characteristics between the two groups. 

A p-value

Their median follow-up times were 24 months (range, 9-60 months) and 16 

months (range, 12-36 months). The median progression free and overall 

survival times were 14.7 ± 2.6 months and 22.4 months ± 3.6 (3-60). The 

1-year and 2-year survival rates were 77% and 41%. The patterns of failure 

was central in 13 of 30 (44%), marginal in 7 of 30 (23%), out-field in 3 of 

30 (10%), and CSF seeding in 7 of 30 (23%). Radiation necrosis observed 

in the MRI occurred in 18 patients (44%). Fourteen patients had grade 1, 3 

patients had grade 2, 1 patient had grade 3. No patient had grade 4 radiation 

necrosis. 

Conclusions: Dose escalation of radiotherapy was feasible in the setting of 

concurrent chemoradiotherapy and resulted in improved survival for glioblastoma. 

Our results deserve further well designed investigation of radiation 

dose escalation study for glioblastoma. 

644 poster 

HYPOFRACTIONATED STEREOTACTIC RADIOTHERAPY OF 

ACOUSTIC NEUROMA (7 X 4 GY): RESULTS AFTER 42 MONTHS 

OF MEDIAN FOLLOW-UP TIME 

M. Kranzinger 1 , F. Zehentmayr 1 , G. Oberascher 2 , F. Merz 1 , O. Nairz 1 , 

H. Rahim 3 , F. Sedlmayer 1 

1 

LANDESKRANKENHAUS SALZBURG, PMU, Radio-Oncology, Salzburg, 

Austria 

2 

LANDESKRANKENHAUS SALZBURG, PMU, Department of Head and Neck, 

Salzburg, Austria 

3 

LANDESKRANKENHAUS SALZBURG, PMU, Department of Radiation Safety 

, Salzburg, Austria 

Purpose: To combine the advantages of short overall treatment time (patient 

comfort, reproducible PTV coverage) and fractionation (reduced late effects 

on cranial nerves) for stereotactic irradiation of acoustic neuroma (AN), 

we initiated a prospective study on hypofractionated stereotactic radiotherapy 

(hSRT) with 7 times 4 Gy. 

Materials: Between 7/2001 and 5/2007, 25 patients (pts) with unilateral 

AN were treated by hSRT (stereotactic system Leibinger-Fischer, Heidelberg 

mask, manually driven 1mm microMLC, software Virtuoso 3.0 DKFZ Heidelberg, 

Germany). Median age was 57,4 yrs (range 32,6 75,6 yrs). Maximal 

extrameatal tumour diameter measured 8-29 mm. Seven pts had surgery 

prior to hSRT, 18 pts had irradiation only.We generated 4-6 fixed microMLC 

beams, to give 4 Gy to the ICRU-reference point for 3-5 fractions per week, 

encompassing the PTV within the 90% isodose volume. PTV was defined 

as GTV plus 1-1,5 mm margin. The median PTV was 0,9 ml (range 0,2 

8,8 ml). Follow up with MRT and audiologic evaluation (Gardner-Robertson 

classes, audiogram with the mean of the 0,5-, 1-, 2- and 3 kHz values) started 

6 months after hSRT and was repeated yearly. 

Results: The volume relation between latest follow up and pretreatment status 

was measured for each pt (fig.: solid line). The dotted line (fig.) shows 

theoretical spherical volume correlations calculated on the basis of real initial 

volumes with an additional 2mm of the diameter of the sphere. This virtual line 

was created for comparison with reported one-dimensional measurements for 

tumour progression (e.g. 2mm increase of the longest diameter). One pt (1 

/ 25) with prior surgery and irradiation of the recurrence showed a 3-fold increase 

of the initial volume and was counted as progress. Hearing pts (n= 

19) showed a deterioration in the audiogram by a median of 14dB (range 

3 27 dB). With a median follow-up of 42 months (mean 37 months) two 

pts showed hemifacial spasm resolving without treatment after 3-11 months. 

One of these pts experienced persistent discrete facial nerve lesion grade III 

(House-Brackmann Scale). No pt developed deterioration of the preoperative 

cranial nerve function or any other new lesion of the ipsilateral facial or 

trigeminal nerve. No pt needed salvage surgery. 


S 211 

Conclusions: Shortening of overall treatment time by hSRT with 7 x 4 Gy is 

feasible in small and medium sized ANs with a local control rate of >95% at 

four years. Only low grade side effects on both hearing capacity as well as 

on the facial nerve were observed. We would like to stimulate our colleagues 

to irradiate pts with GR class I- II hearing early in the course. 

645 poster 

IMPACT ON TOLERANCE AND SURVIVAL OF CONCOMITANT 

RADIOCHEMOTHERAPY IN ELDERLY PATIENTS AFFECTED BY 

GLIOBLASTOMA MULTIFORME (GBM) 

A. Fiorentino 1 , M. Balducci 1 , G. R. D’Agostino 1 , G. C. Mattiucci 1 , S. 

Manfrida 1 , D. Smaniotto 1 , F. Miccichè 1 , G. Mantini 1 , P. Bonomo 1 , S. 

Patriccioli 1 , E. Ippolito 1 , N. Cellini 1 

1 RADIOLOGY, Radiation Oncology, Rome, Italy 

Purpose: We evaluated the tolerance and the efficacy of a conventional 

radiochemo-therapy in elderly patients (>65 years old) with glioblastoma multiforme 

(GBM). 

Materials: Patients with histological proven GBM were treated with 3Dconformal 

radiotherapy. Clinical Target Volume (CTV) was defined on postoperative 

MRI. CTV1 included ring enhancement plus residual tumor if 

present plus 1,5 cm. CTV2 included ring enhancement plus residual tumor if 

present and oedema. PTV1-2 was represented by CTV1-2 plus 0,5cm. Dose 

to CTV1 was 5940 cGy while 3960 cGy was administered to CTV2. All patients 

received concomitant and adjuvant chemotherapy with temozolomide 

(TMZ). Toxicity was evaluated according to RTOG score. Survival analysis 

were based on Kaplan-Meier method and log-rank testing was used for comparison 

of groups. 

Results: From 2000 to 2007, 92 patient with histological proven GBM were 

observed; patients under 65 years were 48 (52.2%) and 44 over 65 years 

old (47.8%). Among the younger patients, median age was 51 years (range 

21-64), 28 were male (59.3%)and 21 female (43.7%). In the elderly group, 

median age was 69 years (range, 65-80), and 18 were > 70 years old; M/F 

ratio was 1:1. In both groups compliance to treatment was 100%. In the 

oldest and youngest group, neurological acute toxicity Grade 1-2 was 9% 

(4/44) and 8,3% (4/48) respectively, while we observed Grade 3 toxicity only 

in the elderly groups (2/44). This difference was not statistically significant. 

At a median follow-up of 25 months (range, 5-75), median progression-free 

survival (PFS) was 10 months in the under 65 yrs patients and 8 months in 

the > 65 yrs patients; no difference was observed ( p=0.9). In the under 65 

yrs group median overall survival (OS) was 17 months and 12 months in the 

> 65 yrs group. One- year and two-year survival was 56% and 22% in the 

oldest group and 65% and 24% in the youngest. (p=0.4). In the elderly group 

(>65) we observed a worse survival in patients over 70 yrs old. Median overall 

survival (OS) was15 months in the under 65, and 9 months in the > 70 years 

old patients. One and two-year survival was 42% and 25% in the upper 70, 

69% and 31% in the under 70 years old patients (p=0,04). 

Conclusions: In our experience age did not represent a limiting factor for 

tolerability. Radical treatment should not be denied to elderly patients but in 

over 70 yrs patients other schedules could be considered.


646 poster 

IS SURVIVAL IN PATIENTS WITH ANAPLASTIC ASTROCYTOMA 

AND GLIOBLASTOMA MULTIFORME REALLY DIFFERENT ATTEND- 

ING RTOG-RPA GROUPS? 

J. Maldonado 1 , M. Ramos 1 , E. Jimenez 2 , A. Ortega 3 , S. Benavente 1 , M. 

Arguis 1 , J. Giralt 1 

1 

HOSPITAL UNIVERSITARI VALL D’HEBRON, Radiation Oncology, Barcelona, 

Spain 

2 

RACSA, Neurosurgery, San Jose, Costa Rica 

3 

HOSPITAL UNIVERSITARI VALL D’HEBRON, Pathology, Barcelona, Spain 

Purpose: The distinction between anaplastic astrocytoma (AA) and glioblastoma 

multiforme (GBM) is important in terms of clinical management, providing 

prognostic information to the patient. Once the combination of temozolamide 

and radiotherapy has became a standard in many centres, recent 

reports in the literature points out inconsistencies in pathological grade and 

clinical outcome when patients are stratified by age, molecular and genetic 

features, imaging or oligodendroglial elements. The purpose of this analysis 

is to test if patients with AA or GBM stratified by RTOG-RPA classes have or 

not a different clinical outcome in our centre. 

Materials: All adult high-grade gliomas treated 1999 2006 were assessed. 

We have previously validated and reported the RTOG-RPA classes outcomes 

in our centre. The same pathologist reviewed all the tumors. A Kaplan Meier 

estimate for survival method was used for median survival time (MST) in 

month (m). We retrospectively analysed MST for AA vs. GMB in different 

prognostic RPA groups. 

Results: 134 of 161 patients were included into the study. 27 patients were 

withdrawn due to irregular follow-up. Mean age was 55,7 year, (range 27 

82); 96 men and 65 women; 18 AA (14%) and 116 GBM (86%). RTOG-RPA 

frequencies were: Group I 6,8%, Group II 1.2%, Group III 13%, Group IV 

36%, Group V 27.4%, and Group VI 14.9%. MST with a 95% C.I. was: Group 

I 49.3 m (24.1, 74.4), N.A for group II. Group III 16.5 m (13.7, 19,3), Group 

IV 8.2 m (5.8 , 10.6), Group V 8.0 m (6.2 , 9.8) and Group VI 5,91 m (2.8 , 

9.0). MST for AA was 25.1 m 95% C.I. (5.5, 44.6) and for all GBM 8.1 m (6.7 

9.4). When analyse only GMB groups II to IV MST was 10.3 m, 95% C.I (7.8, 

12.2). GMB group III MST was 16.5 m(13.7, 19.35). 

Conclusions: In our series AA and GBM have a different clinical outcome in 

terms of MST. Group III GBM have the best results but inferior to AA. RTOG- 

RPA classification remains a useful clinical reference tool despite the new 

gold standard combined strategies. 

647 poster 

LINAC RADIOSURGERY FOR GLOMUS JUGULARE TUMORS 

V. Zaccariotti 1 , J. Paiva 2 , I. Assis 2 , K. Tabata 2 , F. Goulart 3 , J. Arruda 1 

1 HOSPITAL ARAUJO JORGE, Neurosurgery, Goiania, Brazil 

2 HOSPITAL ARAUJO JORGE, Radiotherapy, Goiania, Brazil 

3 HOSPITAL ARAUJO JORGE, Physics, Goiania, Brazil 

Purpose: Despite of being a slow growing hypervascular benign tumor, Glomus 

Jugulare is a challenge for the neurosurgeon, due to its complex localization 

and relation to the cranial nerves. Microsurgery alone or associated 

with radiation therapy has been used for decades, but is frequently associated 

with injury of the lower cranial nerves. In the last decade, radiosurgery has 

been employed to control tumor grow, but long term follow up is still missing. 

The objective of this report is to analize the late results of radiosurgery alone 

in the treatment of glomus jugulare. 

Materials: Three patients with four complex glomus jugulare tumors were 

submitted to radiosurgery as primary therapy. Two men and one woman, this 

one with bilateral lesion, were 78, 60 and 23 years old. The volume of the 

lesions was 2.33, 3.06, 4.92 and 19.6 cc. The primary symptoms were pain 

and there was no cranial nerve dysfunction. The patients received 16 Gy 

to 20 Gy at 90% isodose line, using a Linac with conformal shaped beam 

collimator. 

Results: All patients had important relief of the pain with no more medication 

needed, and a follow up of 71, 67 and 76 months showed slight reduction of 

the lesion in all three patients. The female patient developed a new glomus 

jugulare tumor in the contra lateral side and was submitted again to radiosurgery 

(follow up of 36 months). None patient suffered a lower cranial nerve 

deficit after conformal shaped beam radiosurgery. 

Conclusions: Despite of the small number of cases, long term follow up 

showed that radiosurgery is safe and effective to control tumor grow and to 

reduce pain associated with glomus jugulare. 

648 poster 

LINAC RADIOSURGERY FOR HYPOTHALAMIC HAMARTOMA 

EPILEPSY 

I. Assis 1 , J. Paiva 1 , V. Zaccariotti 2 , K. Tabata 1 , J. Arruda 2 , K. Rezende 3 




Purpose: Usually, medically resistant epilepsy can be treated with surgery to 

disconnect or to make a resection of the epileptogenic area. Often with good 

results and acceptable complications. Radiosurgery is also a established 

treatment to diferent diseases proportioning good results to very low complications. 

However, it is uncertain what produces the control of the epileptogenic 

focus. The hypothalamic hamartoma usually is a clear and evident 

lesion in a epileptogenic area, with good surgical results, but with high morbidity. 

The intention of this report is describe four cases of hypothalamic 

hamartoma epilepsy treated with linac radiosurgery. 

Materials: We treated four male patients with medically untreatable epilepsy 

secondary to hypothalamic hamartoma. They were 3, 8, 16 and 21 years old, 

all of them with daily typical gelastic seizures. These patients treated their 

epilepsy with anti-epileptical drugs and/or surgery proportioning only partial 

control. The 3 years old patient received 6 circular arcs to a volume of 6.7cc 

with a dose of 1600 cGy in a isodose of 80%. The 8 years old patient was 

treated with 16 shaped beams to a volume of 1.8cc. The dose was 1600 cGy 

in a isodose line of 90%. The 16 years old patient was treated the volume of 

1.0cc with 14 shaped beams to a dose of 1600 cGy in a isodose line of 90%. 

The last patient received 12 shaped beams to a volume of 2.0cc to a dose of 

1800 cGy in a isodose of 90%. 

Results: The 3 years old patient had initial results four months after the procedure 

and had a follow up of 54 months until the end of this report. The 

8 years old patient also had initial results four months after the radiosurgery 

and a follow up of 48 months. The 16 years old patient had the initial results 

six months after the treatment and was followed by 10 months. The 21 years 

old patient was followed 36 months and begun the initial results six months 

after the radiosurgery. The Engel Class was I, I, III and II, respectively. None 

complication to date. 

Conclusions: Current options to treat epilepsy includes microsurgery, intersticial 

radiosurgery with I125, radiofrequency ablation and linac based radiosurgery. 

This radiosurgery may act as modulation on hamartoma. The Linac 

based radiosurgery has showed good long term results with safety and low 

morbity. We hope to confirm this in trials with a bigger casuistic. 

649 poster 

LINAC-BASED CONFORMAL RADIOSURGERY OF INTRACRANIAL 

ARTERIOVENOUS MALFORMATIONS; A RETROSPECTIVE STUDY 

Z. Taheri-Kadkhoda 1 , C. Lundqvist 2 , A. Berntsson 3 , S. Hertzman 4 , G. 

Wikholm 3 

1 

SAHLGRENSKA UNIVERSITY HOSPITAL, Jubileumskliniken, Göteborg, 

Sweden 

2 

SAHLGRENSKA UNIVERSITY HOSPITAL, Department of Neurology, 


3 

SAHLGRENSKA UNIVERSITY HOSPITAL, Neuroradiology, Göteborg, 

Sweden 

4 


Purpose: Stereotactic radiosurgery (SRS) is the treatment method of choice 

for intracranial arteriovenous malformations (AVMs) which are not suitable for 

surgery or when total obliteration of the nidus is not achieved with intravascular 

embolizations. The aim of this retrospective study was to evaluate the 

clinical outcomes for patients with intracranial AVMs whom received LINACbased 

conformal SRS at our institution. 

Materials: Since February 1996 to November 2005, 97 patients with intracranial 

AVMs were treated with LINAC-based SRS +/- prior embolizations. The 

median age was 42 years (range, 13-73 ys) with female/male ratio of 1.04 

(50 females /48 males). Majority of the patients were immobilized using the 

Brown-Robert-Wells SRS headframe. Dedicated stereotactic systems (Radionics 

or Brianlab) were used for preparation and delivery of the treatments. 

The prescription dose for majority of the patients was 22 Gy (range, 15-22 

Gy) in a single fraction at isocenter and the treatment was delivered using 6 

MV photons and dynamic arc technique with circular cones or micro multileaf 

collimators. 

Results: A retrospective analysis of the treatment outcomes for the first 40 

patients who had a minimum radiological follow-up of two years revealed a 

total and subtotal radiological obliteration rate of 75% (19 patients with total 

and 11 with subtotal obliterations). Moderate obliteration was achieved in 

seven (17.5%) of the patients and three (7.5%) had no effect of the treatment. 

During the follow-up, one patient suffered from visual impairment and two 

patients complained of memory loss. Only two patients had post-irradiation 

bleeding. 

Conclusions: The preliminary results of using Linac-based SRS for intracranial 

AVMs at our institution reveal that this modality is safe and can yield 

acceptable success rates in obliteration of AVMs. A more update of the treat-

ment outcomes and overview of the predictive factors for treatment success 

concerning the whole cohort of the patients will be presented. 

650 poster 

LINAC-STEREOTACTIC RADIOSURGERY (LSRS) IN THE MANAGE- 

MENT OF TRIGEMINAL NEURALGIA : AN UPDATE OF 51 CASES 

R. Mark 1 , P. Anderson 1 , T. Neumann 1 , M. Nair 1 , S. Gurley 1 , D. White 1 


Purpose: Stereotactic Radiosurgery (SRS) with the Gamma Knife (GK) has 

been used successfully in the treatment of Trigeminal Neuralgia (TN). Results 

have been comparable to open surgery. There have been few reports with the 

use Linac-Stereotactic Radiosurgery (LSRS) in the management of TN. We 

report our updated results with LSRS in the treatment of TN. 

Materials: Between 2000 and 2008, 51 patients with medically refractory 

TN were treated with LSRS. Prior neurosurgical intervention had been performed 

in 39 patients. Twenty two patients had one procedure, 14 patients 

two, and 5 patients three interventions. All patients had typical TN. LSRS was 

given to the cranial nerve V entry root zone into the brainstem. Targeting was 

defined by CT and MRI Scans, and CT Cisternogram, utilizing axial and coronal 

images. Treatment planning was accomplished thru Radionics Treatment 

Planning System. The dose was 87 Gy to Dm, in one fraction using the 5 mm 

collimator and 6 arcs with the 20% Isodose line just touching the brainstem. 

This dosimetry is similar to Gamma Knife. The dose rate was 400 MU/min. 

Average Arc length was 130 degrees. Response to treatment was defined as 

excellent (no pain, off analgesics), good (no pain, with analgesics), and poor 

(continued pain despite analgesics). 

Results: With a median follow-up of 54 months (range 12-98 months), 68.6% 

(35/51) of patients have reported an excellent or good result after LSRS. One 

patient has sustained permanent ipsilateral facial numbness. 

Conclusions: LSRS offers comparable results to GK SRS in the management 

of TN. 

651 poster 

MEDULLOBLASTOMA IN CHILHOOD AND ADULTS: PROGNOSTIC 

FACTORS AND TREATMENT RESULTS: A SINGLE-CENTER EXPE- 

RIENCE 

Z. Ozgen 1 , N. Ozseker 1 , S. Ozgen 1 , S. Bilge 1 , H. Ozyurt 1 , A. Mayadagli 

1 

1 DR. LUTFI KÝRDAR KARTAL EDUCATION AND RESEARCH HOSPITAL, 

Radiation Oncology, Istanbul, Turkey 

Purpose: In this study we evaluated the treatment resuls of medulloblastoma 

patients applied to our clinic and compared the outcomes of children and 

adult age groups. 

Materials: Fiftynine patients with diagnosis of medulloblastoma applied for 

radiotherapy after operation and treated at Radiation Oncology Department 

in Dr. Ltfi Krdar Kartal Education and Research Hospital in between 1997- 

2006 were analized retrospectively. 

Results: Seventeen out of 59 patient ( 29%) over age 18 were grouped as 

adult. Median age of 42 children was 6 (range 2-16), adulthood median age 

was 27 ( 18-52). Of all the patients 39 (66%) were male, 20 ( 34%) were 

female. Total surgical resection were performed in 37/59 (63%) patients, 

remaining patients 22/59 (37%) were undergone subtotal resection. Those 

patients (n= 30/59; 51 %) with totally resected tumor without spread were 

grouped as standart risk. Those patients with more than 1.5 cm residual tumor 

and / or metastasis (n= 29 / 59; 49 %) were evaluted as high risk group. 


S 213 

All patients were applied craniospinal radiotherapy postoperatively. Total cranial 

dose was 36 Gy ( 30-40 Gy) , with additional posteror fossa boost to total 

54 Gy, spinal axis dose was 36 Gy (25- 36 Gy). Chemotherapy was not given 

to any of the adult patient, while 23 (40%) of all children who grouped as high 

risk were applied combined chemotherapy. Age, sex, risk groups, extention 

of surgery, interval between surgery and radiotherapy, duration of total radiotherapy 

were analyzed as prognostic factors in both adult and childhood 

groups. None of them were found to be statistically significant. Median follow 

up of our series was 40 months ( range 6- 120). Median overall survival in 

all ages was 64 months, average 5 year overall survival was 60 %. Average 

disease free survival for 5 year was 49 % and median was 60 months. No 

statistical difference was found for survivals in between childhood and adult 

age groups. 

Conclusions: In our series there was no difference in tumor characteristics 

and radiotherapy doses in between adults and children either standart or high 

risk groups. But in adult patients in high risk group, chemotherapy was not 

used unlike to children. Although small number of adult patients in high risk 

group, 5 year survival was found to be 75 % and there is no sufficient evidence 

for the use of chemotherapy in this group. But small number of adult patients 

in this study makes it difficult to suggest chemotherapy for adults. Further 

studies are needed. 

652 poster 

NO NEGATIVE IMPACT ON SURVIVAL OF PITUITARY RADIOTHER- 

APY IN ACTH PRODUCING ADENOMAS 

G. A. Sattler 1 , A. Van den Bergh 1 , B. Wolffenbuttel 2 , W. Sluiter 2 , G. Van 

den Berg 2 , J. Langendijk 1 , A. Van Beek 2 

1 UNIVERSITY MEDICAL CENTER GRONINGEN/UNIVERSITY OF GRONINGEN, 


2 UNIVERSITY MEDICAL CENTER GRONINGEN/UNIVERSITY OF GRONINGEN, 

Department of Endocrinology and Metabolic Diseases, Groningen, Netherlands 

Purpose: Pituitary radiotherapy (PRT) is widely considered as the most appropriate 

treatment for patients with adrenocorticotropic hormone (ACTH) 

producing adenomas (Cushing’s disease and Nelson’s syndrome) where (repeated) 

pituitary surgery was unsuccessful. Previous studies have suggested 

that PRT for nonfunctioning pituitary adenomas and growth hormone secreting 

adenomas may have a negative impact on survival. However, there is little 

information about the impact of PRT on survival in ACTH producing adenomas. 

The aim of this study was to compare long-term survival in patients who 

are treated for ACTH producing adenomas after surgery with or without PRT. 

Materials: A retrospective study was performed in 78 patients (21 male and 

57 female) treated for Cushing’s disease (n=67) or Nelson’s syndrome (n=11) 

between 1961 and 2007 at the University Medical Center Groningen. Pituitary 

surgery was performed in 74 patients. PRT was given to 31 patients of whom 

21 had Cushing’s disease and 10 Nelson’s syndrome. A total dose between 

45 and 52 Gy was applied with 1,8 to 2,1 Gy daily fractions. The standardized 

survival time (SST) was calculated for the whole cohort and for patients with 

or without PRT and were compared with that of the general Dutch population. 

The standardized survival time provides an age-adjusted estimate of survival 

in each individual, thereby enabling direct comparison between groups. 

Results: Median age at diagnosis was 38 years (range 9-73 yrs). Median 

overall follow-up time was 11 years (range 1-48 yrs). Total cumulative followup 

time was 1008 patient-years. Median follow-up time after PRT was 12 

years (range 129 yrs). Total cumulative follow-up time after PRT was 445 

patient-years. At the end of follow-up, 63 out of 78 (81%) patients were 

alive. The median SST was decreased for the entire cohort (0,84 CI 95%, 

0.74-0.95, p < 0.001). The cumulative survival at half of the individual life expectancy 

was 92% for the general Dutch population. In patients who received 

PRT cumulative survival at half of the individual life expectancy was 75.2%. 

In patients who did not receive PRT this was 73.8% (p=ns). 

Conclusions: Pituitary radiotherapy has no negative impact on survival in 

ACTH producing adenomas. 

653 poster 

OUTCOME AFTER MULTIMODALITY THERAPY AND RADIATION 

DOSE IN SUPRATENTORIAL PRIMITIVE NEUROECTODERMAL 

TUMORS 

J. H. Choi 1 , I. H. Kim 1 , B. K. Cho 2 , H. W. Jung 2 , H. Y. Shin 3 

1 

SEOUL NATIONAL UNIVERSITY HOSPITAL, Radiation Oncology, Seoul, 

Korea Republic of 

2 

SEOUL NATIONAL UNIVERSITY HOSPITAL, Neurosurgery, Seoul, Korea 

Republic of 

3 

SEOUL NATIONAL UNIVERSITY HOSPITAL, Department of Paediatrics, 

Seoul, Korea Republic of 

Purpose: To evaluate the outcome of patients with supratentorial primitive 

neuroectodermal tumors (sPNET) after surgery, radiotherapy, and 

chemotherapy and to identify prognostic factors for survival in this population. 

Materials: Forty-seven patients who underwent surgery for sPNET received


radiotherapy with or without chemotherapy between March 1988 and July 

2006. Median age was 6 years (range, 1-62 years); 29 were males, 18 

females. The tumors were distributed in cortical (39), pineal (5), and thalamic/suprasellar 

(3) regions. Five patients had disease dissemination at 

diagnosis. Complete resection was performed in 28 patients. Adjuvant 

chemotherapy was administered before and after radiation in 41 patients and 

2 patients did not receive complete chemotherapy. All the patients received a 

median dose of 54 Gy (range, 45-56.4 Gy) to the primary tumor site and 40 

patients received craniospinal irradiation (CSI). As for CSI, 23 patients were 

treated with reduced dose (median 23.4Gy; range, 18-24 Gy) and 17 patients 

with standard dose of 36 Gy. 

Results: Median follow-up period was 59 months (range, 9-232 months). 

Overall survival (OS) at 5 years was 77.6% ± 6.3%. Overall progression 

free survival (PFS) at 5 years was 63.6% ± 7.4%. Progression occurred in 

17 patients, with local recurrences in 14, intracranial recurrences in 3, and 

spinal recurrence in 2. In univariate analysis, the factors associated with an 

increase in survival were the localized disease and complete chemotherapy 

by univariate analysis (p = 0.008, 0.009, respectively). There was no statistical 

association between CSI dose and survival. Although not significant (p 

= 0.088), there was a trend toward better survival of those patients with complete 

resection compared with those with incomplete resection. Disseminated 

disease was found to be adverse prognostic factors for survival by multivariate 

analysis (p = 0.016). Of the patients with localized tumor who had have 

complete resection and chemotherapy, OS at was 80.4% with low dose CSI 

and 81.8% with standard dose CSI (p = 0.984). 

Conclusions: Our data suggested that survival of sPNET is good after 

multimodality therapy. In localized sPNETs that was excised completely, 

chemotherapy with reduced dose CSI could result in as same survival as 

standard dose CSI. 

654 poster 

OUTCOME OF DIFFERENT SCHEDULES FOR WHOLE BRAIN 

IRRADIATION OF METASTATIC MELANOMA 

R. Hultborn 1 , J. Ylvén 1 , S. Kinhult 2 , L. Lundgren 2 , U. Stierner 1 , I. 

Turesson 3 

1 INSTITUTE OF CLINICAL SCIENCES, THE SAHLGRENSKA ACADEMY, 

Department of Oncology, Gothenburg, Sweden 

2 DEPARTMENT OF CLINICAL SCIENCES, Oncology, Lund, Sweden 

3 UPPSALA UNIVERSITY HOSPITAL AKADEMISKA SJUKHUSET, Department 

of Oncology, Radiology and Clinical Immunology, Uppsala, Sweden 

Purpose: To analyze the survival after palliative whole brain irradiation for 

metastatic melanoma using different fraction schedules. 

Materials: At one centre (A) 51 patients were treated by lateral opposed 

fields 3.3 Gy twice daily for five consecutive days and at an other centre (B) 

45 patients were treated mainly with 3.0 Gy daily to 30 Gy during two weeks. 

Survival from start of radiotherapy was studied in relation to fractionation, 

age, gender, number of metastases and metastasectomy pre-radiotherapy. 

Results: Survival was dismal at both centres with a median survival of 4.5 

and 3.4 months respectively. Age did not influence outcome in the accelerated 

group while survival for elderly was shortest in the conventionally fractionated 

group. Females fared insignificantly better than males irrespective 

of fractionation. Patients with single brain lesions survived approximately six 

months irrespective of fractionation, the majority after metastasectomy. The 

30-day post-irradiation mortality was similar at both centres (12% and 13% 

respectively). 

Conclusions: No obvious differece in survival between conventional and accelerated 

radiotherapy was found. The burden of the department is similar 

but for the patient the 5 days treatment may be beneficial. 

655 poster 

POSTOPERATIVE STEREOTACTIC RADIOSURGERY WITHOUT 

WHOLE-BRAIN RADIATION THERAPY IN THE TREATMENT OF 

METASTASES TO THE BRAIN 

A. Hartford 1 , N. Simmons 2 , W. Spire 2 , A. Kulkarni 1 , M. Bellerive 1 , K. 

Erkmen 2 , J. Friedman 3 , D. Gladstone 1 , E. Hug 4 , D. Roberts 2 

1 

DARTMOUTH-HITCHCOCK MEDICAL CENTER, Radiation Oncology, 

Lebanon, NH, USA 

2 

DARTMOUTH-HITCHCOCK MEDICAL CENTER, Neurosurgery, Lebanon, NH, 

USA 

3 

TEXAS A&M HEALTH SCIENCE CENTER, Neurosurgery, College Station, 

TX, USA 

4 

PSI, Center for Proton Radiation Therapy, Villigen, Switzerland 

Purpose: Following surgical resection of metastatic brain disease, postoperative 

radiotherapy to the whole brain has been shown to lower the risk of 

tumor recurrence at the site of the original metastasis (10% versus 46% in 

controls), as well as to lower the risk at other sites in the brain (14% versus 

37% in controls) (Patchell et al. JAMA 1998; 280: 1485-1489). For several 

years our institution has offered patients the option of stereotactic radiosurgical 

treatment of the surgical bed as an alternative to whole brain radiotherapy. 

This constitutes our first report of this experience. 

Materials: IRB-approved retrospective chart review was undertaken of patients’ 

records who underwent gross total surgical resection of one or more 

brain metastases followed by focal stereotactic radiosurgery to the surgical 

resection cavity plus margin without whole brain radiotherapy. All patients 

were treated with LINAC-based stereotactic radiosurgery while immobilized 

within an externally fixed, BRW-stereotactic headframe. 

Results: To date retrospective review has identified 43 patients who underwent 

such treatment, between 2002 and 2007. Preliminary analysis of the 

first 13 patients demonstrates local control at the resection cavity site of 10/13 

= 77% with mean follow-up of 13.4 months . Dose delivered to the resection 

cavity averaged 11.8 Gy (mode 10 Gy, range 8.0 18.0 Gy). No relationship 

was seen between dose delivered and local control rate, with average dose 

for controlled lesions 11.6 Gy, while for lesions subsequently recurring the 

average dose was 12.7 Gy (two-tailed t-test = 0.74). 

Conclusions: Preliminary analysis demonstrates good local control rates using 

post-operative stereotactic radiosurgery to the surgical cavity following resection 

of metastatic brain disease. With larger numbers this analysis will be 

more robust. So far, no relationship has been identified between dose and 

local control. Further analysis also will explore recurrence rates and ultimate 

control rates at intracranial sites distant from the surgical resection. 

656 poster 

PRELIMINARY RESULTS OF HYPOFRACTIONATED STEREOTAC- 

TIC RADIOTHERAPY FOR INTRACRANIAL MENINGIOMAS 

F. Trippa 1 , S. Costantini 2 , C. Giorgi 3 , R. Rossi 1 , M. Casale 1 , M. Principi 

4 , I. Aprile 4 , F. Loreti 5 , E. Maranzano 1 

1 

S.MARIA - HOSPITAL, Radiation Oncology, Terni, Italy 

2 

UNIVERSITY SCHOOL OF MEDICINE - TOR VERGATA, Radiation Oncology, 

Rome, Italy 

3 

S.MARIA - HOSPITAL, Neurosurgery, Terni, Italy 

4 

S.MARIA - HOSPITAL, Neuroradiology, Terni, Italy 

5 

S.MARIA - HOSPITAL, Nuclear Medicine, Terni, Italy 

Purpose: Fractionated stereotactic radiotherapy is adopted as an alternative 

to radiosurgery or conformal radiotherapy when meningiomas are incompletely 

excised, surgically inaccessible, or recurrent. We report our experience 

in patients (pts) with intracranial meningiomas treated with hypofractionated 

stereotactic radiotherapy (HSRT). 

Materials: From August 2003 to February 2007, 35 consecutive pts with 

a median age of 59 years (range, 23-86) underwent HSRT for intracranial 

meningiomas using a 5-MV linear accelerator fitted with a commercial dynamic 

micro-multileaf collimator. Male/female ratio was 9/26 and median 

Karnofsky performance status was 90% (range, 60-100). In 16 lesions (44%) 

diagnosis was based upon clinical and radiological data. After surgery or 

biopsy, 19 pts had histologically proven World Health Organization (WHO) 

grade I and 2 pts grade II meningiomas. Eleven lesions (31%) had an incomplete 

resection and 9 (25%) relapsed after surgical excision. The median 

treatment volume was 23 cc (range, 4-58). At the time of HSRT, the 

tumor sites were as follows: cavernous sinus, 9; tubercle of sella, 6; sphenoidal/petroclival, 

5; cerebellopontine angle, 5; orbital 3; other sites, 7. The 

main symptoms on first admission were visual compromise in 51% and cerebellar 

ataxia in 9% of pts. Nineteen (54%) pts received 42 Gy and sixteen 

(46%) pts 45 Gy of total dose, 3 Gy/fraction, 5 fractions/week (the equivalent 

dose in 2-Gy fraction, calculated with an alfa/beta ratio of 3 Gy, is 50.4 Gy 

and 54 Gy, respectively). 

Results: The mean clinical and imaging follow-up period was 24 months 

(range 4-47) and 24 pts had a follow-up >=12 months. At time of analysis, 35 

pts were evaluable for response. Tumor control was achieved in 34 (97%) pts; 

32 (91%) lesions remained stable, 2 (6%) decreased and 1 (3%) progressed 

in size. Median duration of local control was 23 months (range, 4-47). Clinical 

improvement or stabilization of pre-existing neurological symptoms was observed 

in 15 (60%) and in 9 (36%) pts, respectively. A woman with a progression 

of disease after HSRT had worsening of her clinical status. Treatment 

was well tolerated without clinically significant acute and late toxicity. 

Conclusions: Our preliminary data suggest that HSRT can be an effective 

treatment modality for local control of intracranial meningiomas. Hypofractionated 

regimen is safe and feasible, without significant late toxicity. 

657 poster 

PROSPECTIVE EVALUATION OF THE VITAL AND FUNCTIONAL 

OUTCOME OF PATIENTS DIAGNOSED WITH MRI-DEFINED MALIG- 

NANT IMPENDING SPINAL CORD COMPRESSION TREATED BY 

PALLIATIVE RADIOTHERAPY ALONE 

P. Thirion 1 , M. McGarry 2 , G. Rangaswamy 1 , C. Small 1 , O. McArdle 1 , A. 

Clayton-Lea 3 

1 

ST. LUKE’S HOSPITAL, Department of Radiation Oncology, Dublin, Ireland 

Republic of 

2 

ST. LUKE’S HOSPITAL, Clinical Trials Unit, Dublin, Ireland Republic of 

3 

ST. LUKE’S HOSPITAL, Radiotherapy Department, Dublin, Ireland Republic 

of

Purpose: Spinal cord compression represents one of the major cancerrelated 

neurological complications, involving both a vital and functional prognosis. 

The wider availability of MRI and the increased clinician awareness 

have led to an increase in the diagnosis of malignant Impending Spinal Cord 

Compression (ISCC), usually defined as ’The presence of a mass that distorts 

the theca but does not indent or displace the cord.’1 In a retrospective 

analysis, our group already found that the overall survival of patients (pts) 

with ISCC was similar to pts with established spinal cord compression when 

treated by radiotherapy (RT) alone, (median survival respectively 99 days vs. 

105 days) [Clayton-Lea et al, ESTRO 2007]. We present here the preliminary 

results of a prospective observational study assessing the vital and functional 

outcome and survival of pts with ISCC. 

Materials: Since July 2007 all pts diagnosed with ISCC referred for RT to our 

centres were prospectively included in an observational study, agreed by the 

local ethics committee. Eligible pts had cytologicaly/histologicaly proven malignancies, 

an MRI-defined ISCC and were treated by RT alone (no decompressive 

surgery). The mobility status (unaided, with walking aid, bed-bound) 

was evaluated before treatment, then at weeks 1, 5 and 12, by direct clinical 

evaluation or phone call. 

Results: From 30/07/07 to 07/03/08, 6 pts were referred with ISCC. The clinical 

characteristics were as follows: age (median: 72 yrs, [range 47-84]), gender 

(3 female; 3 male), primary tumour sites (Prostate, NSCLC, Renal, Lymphoma). 

The presenting symptoms were pain in all pts (duration range 2-24 

wks) with 3 of the 6 pts reporting constant pain (PVAS range 1-8). None of the 

pts had sensory loss or bladder/anal incontinence at time of referral. All pts 

were exclusively treated by palliative radiotherapy, based on our institutional 

practice (volume: level + 1 to 2 vertebrae, 1 to 2 field class arrangement, dose 

20 Gy/5 daily fractions). Despite treatment, the evaluation at week 5 showed 

a decrease in mobility status associated with bladder incontinence in 3 of the 

six pts. The median survival was similar to previously published (108 days, 

range 35-143 days). Updated results on the above patients, as well as on 

patients presenting within the next 6 months with ISCC will be presented at 

time of the conference. 

Conclusions: This observational study shows that a large proportion of pts 

with ISCC treated by RT alone will develop early, significant neurological deterioration. 

Our current approach regarding treatment and management of 

this cohort of patients warrants further research. This research is supported 

by the St Luke’s Institute of Cancer Research. 1Williams MP, Cherryman GR, 

Husband JE. Magnetic resonance in suspected metastatic spinal cord compression 

Clin Radiol 1988;40:286290. 

658 poster 

RADIOSURGERY FOR CAVERNOUS MALFORMATIONS OF THE 

BRAIN: A PRELIMINARY REPORT OF 23 CASES. 

S. Blamek 1 , D. Larysz 2 , A. Idasiak 1 , K. Ficek 1 , A. Rudnik 2 , L. Miszczyk 

1 , R. Tarnawski 1 


OF ONCOLOGY, GLIWICE, Department of Radiotherapy, Gliwice, Poland 

2 SILESIAN MEDICAL UNIVERSITY, Department of Neurosurgery, Katowice, 

Poland 

Purpose: Background and purpose. Stereotactic radiosurgery (SRS) for cavernous 

malformations of the brain is a controversial method of treatment. Its 

efficiency and safety is still a subject of debate. The aim of the study was 

to evaluate the effect and adverse effects of stereotactic irradiation for brain 

cavernomas. 

Materials: Material. 23 patients; 15 men and 8 women, aged 15-63, mean 

and median age was 38 years. 7 (30.4%) had previous clinically manifested 

hemorrhage, 8 (34.8%) suffered from epileptic seizures, other symptoms 

were: headaches 11 (47.8%), dizziness 9 (39.1%), impaired vision 4 (17.4%), 

paresis 6 (26%), nausea and vomiting 5 (21.7%), impaired speech 2 (8.7%), 

involuntary movements 2 (8.7%). One patient was previously irradiated (28 

Gy in 7 fractions), 5 was operated on (evacuation of hematoma with partial 

removal of the cavernoma). All patients were irradiated with linear accelerator 

equipped with micro-multileaf collimator, the doses applied ranged between 

10 and 20 Gy, mean and median dose were 16 Gy. Median follow-up time 

was 20.6 months. Method. During follow up patients had repeated clinical 

and imaging examinations. The presence of clinical symptoms of bleeding 

and postradiosurgical sequelae were registered. MR and CT examinations 

were used to asses the changes in cavernoma appearance and occurrence 

any radiation -induced damages. Annual hemorrhage risk after treatment was 

calculated using Kaplan-Meier lifetables. 

Results: Results. One patient had hemorrhage after treatment which resulted 

with neurological deterioration. The patient did not have hemorrhage 

before SRS. Annual hemorrhage risk was 2.4% (SE=3.5%), 7.1% (SE=6.4%) 

and 4.3 (SE=5.9%) in the first, second and third year of observation, respectively. 

No hemorrhage was observed in previously bleeding patients. Imaging 

alterations indicating postirradiation damage were present in 7 patients 

(30.4%). In two cases radiation necrosis was diagnosed, in both cases it was 

associated with neurological deterioration, however in one case neurological 

symptoms appeared after hemorrhage. In two patients clinical worsening was 

observed without signs of radiation damage on CT or MRI: headaches and 

facial numbness in one and vision impairment (decreased acuity and double 


S 215 

vision) in the other (lesion located in tectal plate). 

Conclusions: Conclusions. SRS, because of its unproven value, is not a 

standard treatment modality for cavernomas in our center. Although hemorrhage 

rate after SRS is low in the presented material, the risk of radiation 

damage is considerable. Further investigation is required to establish the 

value of SRS in the treatment of cavernous malformations. 

659 poster 

RADIOSURGERY FOR THE TREATMENT OF BRAIN METASTASES: 

RPA, SIR AND PROGNOSTIC FACTORS 

T. Antunes 1 , P. Ravasco 2 , V. Mendonca 1 , M. Fortunato 1 , I. Monteiro Grillo 

1 

1 HOSPITAL DE SANTA MARIA, Serviço de Radioterapia, Lisbon, Portugal 

2 INSTITUTO DE MEDICINA MOLECULAR, FACULDADE DE MEDICINA DA 

UNIVERSIDADE DE LISBOA, Unidade de Nutrição e Metabolismo, Lisbon, 

Portugal 

Purpose: Reliable and feasible prognostic factors are necessary to identify 

homogeneous patient populations, allowing a correct therapeutic orientation 

according to the possible disease and treatment outcomes. Thus our purpose 

was to evaluate the value of using Recursive Three Analysis (RPA) vs Score 

Index for Radiosurgery (SIR) in the therapeutic guidance according to the 

prognosis of patients with brain metastases (BM) submitted to Radiosurgery 

(RS). 

Materials: This study comprised a retrospective analysis of 87 patients with 

BM who underwent RS between August 1995 and August 2007. Mean age 

was 56.8 (36{82) years and mean Karnofsky Index (KI) was 80 (40{100); 75 

patients were submitted to whole brain radiotherapy (WBRT){30Gy in 10 fractions, 

followed by RS. The remaining patients were only submitted to RS. The 

mean lesion volume was 3.72 (0.07{15.0) cm3; the mean marginal doses was 

18 (10{20) Gy. On average 1 (1{4) brain lesion was treated. Before RS, 80 

(91.9%) patients had controlled primary disease. The evaluated prognostic 

factors included: age, KI, extra cranial disease, number of BM, volume of 

the biggest lesion, doses and WBRT. The survival curves were calculated after 

stratification for the RPA/SIR classes, in order to determine their potential 

prognostic value. 

Results: Median survival was 8 (1{44) months; 3 patients were lost to followup; 

76 patients died: 61 (80.2%) due to disease progression/metastatic disease; 

6 (7.9%) with local progression of the irradiated lesion and 9 (11.9%) by 

concurrent disease. The patient distribution by RPA classes was: 1 (n=69), 2 

(n=16) and 3 (n=2), p


Conclusions: TMZ given as concomitant to RT and as maintenance treatment 

in Pts with GBM has shown to be effective and well tolerated in adjuvant 

setting. Further follow-up and larger number of Pts will be required to define 

its concrete advantage on survival. 

661 poster 

RADIOTHERAPY WITH CONCOMITANT AND ADJUVANT TEMO- 

ZOLOMIDE IN GLIOBLASTOMA MULTIFORME PATIENTS: A 

PROSPECTIVE STUDY 

S. Sarihan 1 , S. Yildirim 1 , H. Ozturk 1 , T. Evrensel 2 , H. Kocaeli 3 , S. 

Tolunay 4 

1 

ULUDAG UNIVERSITY, FACULTY OF MEDICINE, Radiation Oncology, Bursa, 

Turkey 

2 

ULUDAG UNIVERSITY, FACULTY OF MEDICINE, Medical Oncology, Bursa, 

Turkey 

3 

ULUDAG UNIVERSITY, FACULTY OF MEDICINE, Neurosurgery, Bursa, 

Turkey 

4 

ULUDAG UNIVERSITY, FACULTY OF MEDICINE, Pathology, Bursa, Turkey 

Purpose: We conducted a prospective study in patients (pts) with glioblastoma 

multiforme (GBM) who underwent surgery followed by radiotherapy (RT) 

plus concomitant and adjuvant temozolomide (TMZ). 

Materials: Between February 2005 and September 2007, we selected 26 

pts with newly diagnosed GBM underwent surgery followed by RT plus concomitant 

and adjuvant TMZ. Radiotherapy was applied with a median dose of 

60 Gy (58-60 Gy), in 30 fractions over 6 weeks along with concomitant TMZ 

(75 mg/m2) daily followed by 6 cycles of adjuvant TMZ (150-200 mg/m2 for 5 

days during each 28-day cycle). 

Results: All patients evaluated at January 2008. Median age was 54 years 

(27-70 years); 20 pts were male and 6 were female. Thirty percent of pts 

underwent a total resection of tumor and 70% had partial resection. Five pts 

had neurologic deficite and 8 pts had seizure prior the treatment. The postoperative 

median Karnofsky Performance Status (KPS) was 90 (70-100). All pts 

received concomitant RT and TMZ. Radio-chemotherapy was well tolerated 

with 8% (2/26 pts) developing grade 3 thrombocytopenia, 4% (1/26 pts) elevated 

hepatic enzymes and 4% (1/26) allergic reaction respectively during the 

treatment and could be completed without interruption in 22 of 26 pts (84%). 

Six pts did not received adjuvant TMZ due to rapid progression. Adjuvant 

TMZ were given to 17 pts with median 3 cycles (1-6 cycles). In the evaluation 

time 3 pts have been continued to receive adjuvant TMZ. In 13 pts the 

adjuvant TMZ was not completed due to progressive disease in 53% (9/17), 

grade 3-4 hematologic toxicity in 18% (3/17), and and rush in 6% (1/17) of 

the pts. After treatment, median KPS was found 90 (90-100) and improved of 

neurologic deficits by 80% (4/5 pts). Assesment of response was done radiologically 

6 weeks after the completion of RT, objective response was obtained 

in 15 pts (58%) (partial response: 1 pt, NED: 7 pts, stabil disease: 7 pts). 

One patient was not evaluated for response. Tumor progression was seen in 

10 pts and 8 pts underwent to reoperation. At a median follow-up 12 months, 

1-year survival was 68%. The median overall (OS) and progression-free survival 

(PFS) was 18 and 6 months, respectively. The median progression time 

was 2 months (1-10 months). Both the median OS and PFS rates were found 

higher in pts who received adjuvant chemotherapy, significantly (21 vs. 10 

months and 10 vs. 1 month, p=0.001, p and < 80 mm2, respectively, were 

evaluated. 

Results: In the group receiving a marginal dose of 20 (+/- 1) Gy, the mean 

tumor size decreased rapidly until 2 months, and thereafter remained stable 

or continued to decrease gradually, regardless of the tumor size. On the 

other hand, in patients with a tumor size > 80 mm2 treated with 15 (+/- 1) 

Gy, the mean tumor size decreased at 1 month but tended to increase thereafter. 

Tumors < 80 mm2 diminished gradually after a 15-Gy dose. Small cell 

carcinomas and squamous cell carcinomas of the lung shrank faster than did 

adenocarcinomas of the lung. However, local control rate did not seem to differ 

significantly between squamous cell carcinomas and adenocarcinomas. 

There were no difference in the regression curves between metastases from 

lung adenocarcinoma and those from breast cancer. 

Conclusions: The mean tumor size decreased until 2 months after GKS. 

Squamous cell carcinoma regressed more rapidly than did adenocarcinomas, 

but the local control rate was not different between the two. Differences according 

to the primary tumor site were unclear. 

664 poster 

RESULTS FROM 447 PATIENTS TREATED WITH COMBINED- 

MODALITY THERAPY FOR GLIOBLASTOMA MULTIFORME (GBM) 

AT THE MEDICAL UNIVERSITY OF VIENNA 

A. Rottenfusser 1 , M. Preusser 2 , G. Altorjai 1 , R. Bartsch 2 , C. Luetgendorf- 

Caucig 1 , M. Hassler 2 , T. Czech 3 , J. Hainfellner 4 , C. Marosi 2 , R. Pötter

1 , K. Dieckmann 1 

1 


Austria 

2 

MEDICAL UNIVERSITY OF VIENNA, First Departement of Medicine and 

Cancer Centre, Vienna, Austria 

3 

MEDICAL UNIVERSITY OF VIENNA, Department of Neuro-Surgery, Vienna, 

Austria 

4 

MEDICAL UNIVERSITY OF VIENNA, Department of Neuro-Pathology, 

Vienna, Austria 

Purpose: Since 1994, patients diagnosed with GBM at the Medical University 

of Vienna and Karnofsky Performance Score ≥70 received a combination of 

neuro-surgical resection, irradiation and chemotherapy. Soon, major differences 

in outcome became evident. We therefore investigated if the introduction 

of temozolomide (TMZ) as well as other factors, including haemoglobin 

levels (Hb), high lactate-dehydrogenase (LDH) levels as potential surrogate 

for increased tumour vasculature, and proliferation rate may predict outcome. 

Materials: Four-hundred forty-seven patients were available for this analysis. 

Preoperative LDH, Hb, and MRI-scans as well as histological samples were 

available. Proliferation rate was estimated by the immunohistochemical assessment 

of nuclear antigen Ki-67 with MIB-1 antibody. We used a cut-off of 

>=20% to define tumours with high proliferation rate. All patients received a 

postoperative 3-D-conformale irradiation of the primary tumour region with a 

safety margin of 10 to 15 mm. Chemotherapy consisted of CCNU, fotemustine 

/ dacarbacine, or TMZ. Following primary treatment, MRI-scans were 

conducted every three months. Progression-free survival (PFS) and overall 

survival (OS) were estimated using the Kaplan-Meier product-limit-method. 

The log-rank test was used to test differences between curves. Factors significantly 

associated OS were analysed in a Cox regression model. 

Results: Median age was 63.7 years (y) (range [r] 24-85 y). 146/447 (32%) 

underwent total resection; reminders had tumour biopsy or subtotal resection 

only. Median PFS was 0.6 y (r 0.04-8.33 y; 95% CI 0.52-0.69). Median OS 

was 1.05 y (r 0.05-8.39; 95% CI 0.94-1.16). In the Cox regression model, age 

< 65 y (p=0015), treatment with TMZ (p=0.012), and total resection (p=0.021) 

were significantly associated with longer OS. 

Conclusions: Our results are well in line with data from different other studies, 

demonstrating a benefit for younger patients as well as for those treated 

with TMZ. Elevated LDH levels and high proliferation rate may define a subgroup 

of patients with worse outcome. Final results will be presented at the 

meeting. 

665 poster 

RISK FACTORS OF VISUAL COMPLICATIONS AFTER FRACTION- 

ATED STEREOTACTIC RADIOTHERAPY 

B. Baumert 1 , R. Houben 2 , G. Bosmans 2 , J. Jager 2 , T. Veninga 3 , A. 

Theelen 2 , R. Debougnoux-Huppertz 2 , P. Lambin 1 

1 

UNIVERSITY HOSPITAL MAASTRICHT, Dept. Radiation-oncology (MAAS- 

TRO), GROW (Research Institute Growth and Developm, Maastricht, 

Netherlands 

2 

UNIVERSITY HOSPITAL MAASTRICHT, Dept. Radiation-Oncology (MAAS- 

TRO), Maastricht, Netherlands 

3 

DR. BERNARD VERBEETEN INSTITUUT, Dept. of Radiation Oncology, 

Tilburg, Netherlands 

Purpose: To examine potential risk factors and the 3D dose distributions of 

the chiasm and optic nerves in relation to visual complication rate. 

Materials: Seventy-five patients (median age 57 years) of more than 215 patients 

treated by stereotactic radiotherapy (SCRT) between 2003 and 2007 

with fractions of 1.8 Gy and an inclusion of optic nerves and/or chiasm have 

been identified. Doses given to the optic system range between 5-105% of 

the prescribed dose (mean total dose 53.2 Gy). Mean and median follow-up 

was 21.3 and 17.5 months, respectively. For 6 patients (3 pituitary adenoma, 

1 suprasellar meningioma, 1 glioma, 1 craniopharyngeoma) a decrease in 

vision and/or visual fields between 11 and 36 months after SCRT has been 

documented. Risk factors taken into account were tumour resection, hypertension, 

diabetes mellitus, age and dose-volume relations. SCRT is based 

on MRI scan with 1 mm voxels and 3D planning. Dose-volume-histograms 

for small volumes were calculated with grid sizes of 1-2 mm. Potential risk 

factors were identified with univariate analyses (Chi-square for dichotomous 

and Mann-Whitney U for continuous variables), and subsequently reduced 

in a backward logistic regression analysis (with validity determined by the 

Hosmer-Lemeshow test). Because of the small number of patients with visual 

complications, all analyses were carried out with α=0.1. 

Results: Total doses > 50 Gy received 48.2% (mean) of the chiasm in 42 

patients, 16.3% of the left optic nerve in 23 patients, 12.4% of the right optic 

nerve in 21 cases, 17.6% part of the left and right optic nerve, respectively. 

Mean maximum doses were 39.2 Gy to the chiasm, 27.6 Gy to the left optic 

nerve, 28.0 Gy to the right optic nerve and 33.3 Gy to part of both optic 

nerves, respectively. Maximum chiasm dose was for patients with visual toxicity 

median 52.7 Gy (52-63 Gy), for patients without toxicity 50.2 Gy (2-60 Gy). 

to Univariate analysis found tumour resection, partial irradiation of the chiasm 

with a dose > 50 Gy, minimum and maximum dose to the chiasm, maximum 

dose to the right optic nerve and age in years as significant risk factors. Mul- 


S 217 

tivariate analysis confirmed only age (p=0.03, OR 1.1 per year), and tumour 

resection (p=0.033, OR 13) as significant prognosticators. The probability of 

a visual complication can be determined as follows: the higher the age the 

higher the risk for a visual complication. Patients irradiated after a resection 

are at higher risk. The model was internally valid (Hosmer-Lemeshow Chi 

2.97; df=7; p=0.89). 

Conclusions: We could identify in this patient group age and tumour resection 

as a risk factor for visual toxicity. Higher age is presumably an indicator for 

increasing incidence of cerebro-vascular diseases which adds to the vascular 

injuries inflicted by radiotherapy. Maximum total doses to the optic system 

should be kept below 50 Gy and ≤ 1.8 Gy per fraction especially for SCRT of 

benign brain tumours 

666 poster 

ROLE OF RADIOTHERAPY IN INTRACRANIAL HEMANGIOPERICY- 

TOMA 

J. Lee 1 , I. H. Kim 1 

1 SEOUL NATIONAL UNIVERSITY HOSPITAL, Radiation Oncology, Seoul, 


Purpose: Intracranial hemangiopericytoma originated from perivascular pericytes 

is a rare neoplasm. Intracranial hemangiopericytoma is known as highly 

recurrence or metastasis rates. A retrospective study was performed to evaluate 

the role of radiotherapy in intracranial hemangiopericytoma. 

Materials: Medical records of 23 patients with intracranial hemangiopericytoma 

who were treated from February 1987 to August 2007 in Seoul National 

University Hospital were retrospectively reviewed. Twelve patients were 

treated by operation only and 11 patients by operation with adjuvant radiotherapy. 

Extent of surgical resection was gross total resection (GTR, n = 15) and 

subtotal resection (STR, n = 8). Radiotherapy technique was delivered with 

conventional radiotherapy (n = 5) and conformal radiotherapy (n = 6). Adjuvant 

radiotherapy was performed to 7 patients underwent STR and 4 patients 

underwent GTR. The median follow-up period was 48 months (range 1-203). 

Results: The 5, 10 and 15-year overall survival rates were 96%, 96% and 

20%. The 5 and 10-year progression free survival rates (PFS) were 73% and 

24%. The median PFS was 82 months (range 1-129). Of the 23 patients, 

6 had local recurrences (LR), 2 had LR with distant metastasis (DM), and 1 

had DM. PFS tended to be better without significance in cases with female, 

old age, good performance status (ECOG 0,1) and small tumor (< 5 cm). The 

5-year PFS for patients treated with GTR and STR were 92% and 33% (p = 

0.025). The median PFS was 112 months for operation group and 77 months 

for operation with adjuvant radiotherapy group (p = 0.054). The 5-year PFS 

for patients treated with GTR, GTR with adjuvant radiotherapy and STR with 

adjuvant radiotherapy was 100%, 75% and 38% (GTR vs. STR with adjuvant 

radiotherapy, p = 0.048 and GTR with adjuvant radiotherapy vs. STR with 

adjuvant radiotherapy, p = 0.430). 

Conclusions: Initial complete resection of tumor is most important for treatment 

of intracranial hemangiopericytoma. Adjuvant radiotherapy is necessary 

for patients treated with incomplete resection of tumor. 

667 poster 

SIMULTANEOUS INTEGRATED BOOST IN RADIOTHERAPY OF 

GLIOBLASTOMA MULTIFORME: EARLY EXPERIENCE ON 10 

CASES 

A. Urgesi 1 , U. Monetti 1 , A. Mussano 1 , S. Gribaudo 1 , S. La Sala 1 , A. 

Sardo 1 , V. Richetto 1 , E. Madon 1 

1 OIRM S.ANNA, Radiation Oncology, Torino, Italy 

Purpose: Local and marginal recurrence account for the majority of failures 

after RT for GBM. Dose escalation however has failed to show a clear survival 

benefit. Recently the combination of RT with concomitant and sequential 

Temozolomide (TMZ) has become standard treatment after having shown a 

significant survival improvement in randomised trials. RT dose escalation has 

not been extensively tested in this new contest. The purpose of this study is 

to explore the feasibility of dose escalation through a simultaneous integrated 

boost in patients treated with concomitant and sequential TMZ. 

Materials: Ten pts (6 M, 4 F, median age 56) referred to our department for 

RT after surgery for GBM were enrolled in the study. All pts had residual 

disease at the start of RT, none was under steroid therapy and all were in 

good performance status (ECOG 0-1). GTV was defined as the contrastenhancing 

mass at MR; CTV was GTV + 2 cm and PTV was CTV + 0.5 

cm. All pts were immobilized with rigid thermoplastic masks and localized 

stereotactically. IMAT employing a micromultileaf collimator with 5 mm leaves 

was used in all pts. Dose prescriptions were 1.8 Gy/fraction to PTV and 2.5 

Gy/fraction to GTV; total dose was 59.4 Gy to PTV and 82.5 Gy to GTV in 33 

fractions. Mean GTV volume was 43+7 cc. The mean Paddick CI was 0.65+3 

for both PTV and GTV. Mean EUD (a/b: 10) was 71.19+1.65 Gy to PTV and 

79.09+1.69 Gy to GTV. Pts were seen at weekly intervals during treatment, 

monthly in the following 3 months and at 3 month intervals thereafter. A first 

evaluation MR was performed 45-60 days after the end of treatment. All pts 

gave informed consent to the study.


Results: All pts completed treatment in the prescribed time (mean duration: 

46+1 days). No patient required steroid therapy during treatment nor in the 

first 3 months after therapy. Mean follow-up is 3 months (range:1-6). A major 

response at first evaluation (> 70% reduction of the CE area) was observed 

in 3 pts, a minor response (25-50% reduction) in 2 and stable disease in 5. 

One pt showed progression requiring steroids at 6 months. All pts are alive 

at the moment of this report. 

Conclusions: Dose escalation through simultaneous integrated boost is feasible 

in a population of pts with GBM in good PS. The major clinical advantage 

of this approach is increased GTV dose without increasing of overall 

treatment time. Results are too preliminary to allow meaningful evaluation 

although the observation of 3 major responses is encouraging. 

668 poster 

STEREOTACTIC RADIOSURGERY (SRS) - THE PATIENTS PER- 

SPECTIVE 

R. Smee 1 , J. Williams 1 

1 THE PRINCE OF WALES CANCER CENTRE, Department of Radiation 

Oncology, Randwick, Australia 

Purpose: There is now extensive literature demonstrating the objective benefit 

of SRS for intracranial and skull base lesions. Quality of life compared to 

surgery may also be favourable. This study aims to chart the patients perspective 

of this procedure. 

Materials: A 3-phase diary study was prospectively initiated in March 2005, 

after the experience of the previously treated 100 patients was evaluated. 

The phase-1 diary establishes the patient perspective 24 hours after treatment, 

phase-2 at one week and phase-3 at 3 months post SRS. The diary 

investigates the symptom profile, emotional functioning and mood state at 

these time frames using the Likert scale. The expectation was that any adverse 

features related to the procedure would subside quickly post SRS. The 

specific aim of the project was to evaluate the physical, psychological and 

social well being of the patient post treatment. 

Results: In this ongoing study 224 patients were evaluated with the last 

patient completing the study in January 2008. Cerebral metastases were 

the dominant condition (36.6%), followed by meningiomas and vestibular 

schwannomas. 206 patients completed phase-l & 2 (92%), 184 completed 

all 3 phases (82%). 22 palliatively treated patients (11%) were too ill to complete 

the study, and 20 (10%) diaries were not returned. Pleasingly 100% 

noted their procedure management was "exceptional", 10% found application 

of the head-ring was ’horrendous’, but 60% indicated they would repeat the 

process for a positive outcome. Loss of concentration and balance scored 

high on the Likert scale throughout all phases, with 91% still experiencing 

fatigue at 3 months post SRS. 

Conclusions: The patient experiences the procedure different to the clinician’s 

expectation. Fatigue continues for up to 3 months post treatment for 

the great majority of patients. Further investigation is warranted. 

669 poster 

STEREOTACTIC RADIOSURGERY FOR ACOUSTIC NEUROMA: A 

SINGLE INSTITUTION EXPERIENCE 

P. Anselmo 1 , M. L. Basagni 1 , F. Trippa 1 , M. Casale 1 , R. Rossi 1 , L. 

Chirico 1 , S. Costantini 2 , C. Giorgi 3 , E. Maranzano 1 

1 


2 


Rome, Italy 

3 

S.MARIA - HOSPITAL, Neurosurgery, Terni, Italy 

Purpose: The clinical outcome and toxicity of stereotactic radiosurgery (SRS) 

was assessed for acoustic neuroma in 53 patients (pts) treated in our institution. 

Materials: Between September 2001 and January 2008, 53 pts (median age: 

60; range: 23-85) with acoustic neuroma underwent stereotactic radiosurgery 

(SRS) using a 5-MV Linac fitted with a dynamic micromultileaf collimator. 

Thirty-nine (73.5%) pts received SRS alone, and remaining fourteen (26.5%) 

were treated with SRS after surgery: 5 (36%) pts had a relapse, 9 (64%) 

a residual disease. Before SRS, 40 (75.5%) pts had deficit of hearing only 

(Gardner-Robertson classes 2, 3 and 4), 10 (19%) pts had postoperative V 

and or VII cranial nerves deficits, and 3 (5.5%) pts had no symptoms. The 

median target volume was 1.7cc (range 0.1-7.40), the planning target volume 

(PTV) included the tumor mass evidenced at the magnetic resonance imaging 

(MRI) with a margin of 1 mm. Single doses of 13-20 Gy (median 17 Gy) 

were prescribed at the PTV isocentre. The follow-up consisted of a first MRI 

after 3-6 months from SRS, followed by MRI, a hearing test and a neurological 

examination, every 4 months. 

Results: Thirty of 53 pts (57%) have a follow-up longer than two years (24- 

66 months). No acute toxicity was observed. Nine (30%) pts presented late 

toxicity that consisted in a mild and transient trigeminal and facial morbidity. 

Two (22%) pts developed a complete facial nerve palsy, while five (66%) 

presented a radiation-induced trigeminal neuralgia. Twenty five (83%) pts reported 

a clinic response (ie, steady state or improvement) to the treatment, 

five (17%) pts worsened in hearing capacity. Examining MRI response, 28 

(93%) pts presented an instrumental response (ie, shrinkage or stable disease), 

and only 2 (7%) pts developed a progression of disease. The hearing 

preservation rate in patients with useful hearing before SRS was 63% at 2 

years. The toxicity appears to be directly correlated to the dose and tumor 

size. In fact, pts who developed late toxicity were treated with high doses 

(median dose 17.5 Gy) and had masses greater than 4 cc. 

Conclusions: In our experience, SRS results in a good local control rate of 

acoustic neuroma with a risk of cranial nerve toxicity slightly superior to that 

reported in literature. To reduce late toxicity, SRS is now reserved to small 

lesions and prescribed doses not exceed 15 Gy. 

670 poster 

STEREOTACTIC RADIOTHERAPY FOR NONFUNCTIONING PITU- 

ITARY ADENOMAS - A BRAZILIAN EXPERIENCE 

J. Paiva 1 , V. Zaccariotti 2 , I. Assis 1 , J. Arruda 2 , K. Tabata 1 , V. Araujo 3 , 

N. Freitas 1 , J. Pinezi 1 , W. Abreu 1 




Purpose: Transsphenoidal surgery is the main management of nonfunctioning 

pituitary adenomas (NFA). However, a significant number of NFAs will recur 

and so require additional treatment. Conventional radiotherapy (CRT) is 

commonly used in incompletely resected or recurrent NFAs with a long-term 

tumor control in up to 90% of patients. In spite of this, there are concerns 

about the real necessity and potencial toxicityof CRT and its use remains 

controversial. Stereotactic radiation techniques have been used in NFAs in 

order to minimize pos-radiation long-term complications. In this article, we encompass 

an analysis of all consecutive patients who were treated with linac 

based stereotactic radiotherapy for NFAs, focusing onradiologic tumor control 

and actinic toxicity. 

Materials: From 2003 through 2007, 10 patients who had nonfunctioning pituitary 

adenoma were treated with linac based stereotactic radiotherapy. The 

software components of treatment planning required stereotactic computed 

tomography (CT) and magnetic resonance imaging (MRI) images. The irradiation 

system used a micromultileaf collimator apparatus in a standart linear 

accelerator 6MV photons. After the treatment completed all patients were 

followed with CT and/or MRI studies, when we determined response as reduction 

from at least 25% in the greatest tumor dimension compared with 

baseline radiographic study. Stabilization as a reduction or a increase until 

25% in the tumor dimension, and progression as a increase to at least 25%. 

Complete response was defined when studies displayed no tumor tissue. 

Results: Five patients were male and five were female. The age range was 

from 44 to 76 years old (mean 57.2 years). The mean follow up was 35.2 

months (range from 4 to 84 months). Intrasellar extension in association with 

extrasellar tumor extension was documented in 3 of 10 patients (30%). Five 

patients had extrasellar adenoma (50%) and two patients had intrasellar adenoma 

(20%). Cavernous sinus infiltration ocurred in 6 cases (60%). The volume 

treated varied between 0.59cc and 34.01cc (mean 7.02cc). Total dose 

of radiation was from 40 to 58Gy (mean 53.6Gy), and daily fraction 180 or 

200cGy. Mean maximum dose prescribed in tumor was 2.06Gy (range from 

1.89 to 2.32Gy), and mean minimum dose prescribed was 1.76Gy (range 

from 1.58 to 1.96Gy). Only three patientes suffered mild headache as acute 

toxicity, and two patients evolved to hypopituitarism as late toxicity. Four patients 

were considered responsive (40%) and six patients stable (60%). 

Conclusions: Stereotactic treatment offer a more localized irradiation when 

compared with CRT and the reported results suggest efficacy and potential 

reduction in long-term morbidity. However, is not clear if that is due to short 

follow up or small number of patients. As well, there is a need for prospectives 

trials to compare efficacy and toxicity of different stereotactic techiniques. 

671 poster 

THE CAUSE OF DEATH OF THE RPA CLASS 1 BRAIN METASTASES 

TREATED BY STEREOTACTIC RADIOSURGERY 

M. Takahashi 1 , T. Inomata 1 , T. Shimbo 1 , Y. Uesugi 1 , I. Narabayashi 1 

1 OSAKA MEDICAL COLLEGE, Radiology, Osaka, Japan 

Purpose: We clarified the cause of death of the patients treated by stereotactic 

radiosurgery with brain metastases classified RPA class 1. 

Materials: Between December 1998 and February 2007 we treated 233 patients 

with brain metastases by stereotactic radiosurgery (SRS). By classification 

of RTOG recursive partition analysis (RPA), 25 patients were classified 

RPA class 1, 151 patients were classified class 2, and 57 patients were 

classified class 3. We investigated the cause of RPA class 1 patients’ death 

retrospectively, and considered the characteristics of not so good prognostic 

patients. 

Results: The mean age of 25 patients was 57.5 years old. Sixteen were 

males and 9 were females. The primary site of 22 patients was lung. The 

median survival time of these 25 patients was 31 months, 3-year and 5-year 

survival rate was 49.0% and 13.1%, respectively. Six patients were alive and

19 were died. The cause of their death was brain recurrence (n=6; 31.6%), 

distant recurrence (n=7; 36.8%), primary site recurrence (n=2; 10.5%), and 

pneumonia (n=1; 5.3%), and 2 patients’ cause of death were unknown. The 

sites of metastases after SRS were brain (17), bone (9), liver (2), and adrenal 

gland (1), and 5 patients did not have any metastasis. Although 68% of RPA 

class 1 patients had brain metastases after SRS, only 35.3% of these patients 

were died of neurological cause. 

Conclusions: The common causes of death of the patients treated by SRS 

with brain metastases classified RPA class 1 were distant recurrence (36.8%) 

and brain recurrence (31.6%). Seventeen patients had brain metastases after 

treatment by SRS, nevertheless, only 6 patients of there were death from 

brain metastases. 

672 poster 

VALIDATION OF RTOG-RPA GROUPS IN HOSPITAL UNIVERSITARI 

VALL D’HEBRON (HUVH) FOR HIGH GRADE GLIOMAS (HGG) 

J. Giralt 1 , M. Ramos 1 , J. Maldonado 1 , E. Puertas 1 , E. Jimenez 2 , S. 

Benavente 1 , M. Arguis 1 

1 H.U. VALL D’HEBRON, Barcelona, Spain 

2 RACSA, San Jose, Costa Rica 

Purpose: The RTOG RPA groups have been adopted as a survival reference 

for clinical practice and research. In order to design a survival reference 

baseline for HUVH clinical trials, we analyzed our experience treating HGG 

to test if it fits with the survival RTOG published results. 

Materials: We retrospectively reviewed the clinical features and median survival 

time of all the HGG patients treated in HUVH from 1999 to 2006. We 

classified them by RTOG RPA classes and we calculated the median survival 

time (MST) by Kaplan-Meier method. We compared the survival results 

between the patients from our centre and those from RTOG. 

Results: We included 134 of 161 patients into the MST analysis. There were 

27 patients without enough data. The mean age at diagnosis was 55.76 years 

old and there were 96 men and 65 women. The histopathology diagnosis 

were anaplastic astrocytoma (AA) in 18 (14%) and glioblastoma multiforme 

(GBM) in 116 (86%). The mean of Karnofsky status for all patients was 84%. 

The proportion of RPA groups and MST in months with the 95% CI are shown 

in the following table: 

Conclusions: Although in some situations we had difficulties to classify the 

patients into the RPA groups, in general RTOG-RPA groups fits quite well 

regarding our dataset.For groups III to VI we obtained slightly superior MST 

results regarding RTOG data. For group II we decided not to analyze the data 

because of the small sample. For group I we obtained inferior results probably 

artefacted by the small sample size for this group. In order to establish a 

baseline survival for clinical research, every centre should review its own data. 

673 poster 

WEEKLY ALTERNATING TEMOZOLOMIDE AFTER CHEMO- 

RADIOTHERAPY IN OPERATED HIGH GRADE GLIOMAS: RESULTS 

IN 34 PATIENTS 

S. Dall’Oglio 1 , A. D’amico 1 , F. Pioli 1 , M. Palazzi 1 , M. Gabbani 1 , S. 

Maluta 1 

1 UNIVERSITY HOSPITAL, Radiotherapy, Verona, Italy 

Purpose: The prognosis of newly diagnosed high grade gliomas (HGG) after 

surgery is still dismal. The standard chemo-radiotherapy regimen yields a 

two-year survival rate of 26.5%. Dose-dense regimens have been applied 

in relapsed HGG, and the weekly alternating one showed low toxicity. We 

performed a new phase II trial enrolling patients with newly diagnosed HGG, 

to test the efficacy of a weekly alternating TMZ schedule after surgery and 

concomitant chemo-radiotherapy. 

Materials: From October 2005 to April 2007, 34 patients (21 males, 13 females; 

age 30-70, mean age 53) were enrolled in the study. The local ethics 

committee approved it. The main inclusion criteria were prior surgery for HGG 

(histology proven), age more than 18 years, Karnofsky performance status 


S 219 

(KPS) of 60 or more, no alteration on bone marrow reserve, liver function, 

or renal function. Each patient was assigned to a RPA HGG class according 

to the RTOG classification (zero to 12). Concomitant chemo-radiotherapy 

started within 6 weeks after surgery. Radiotherapy consisted of 2 Gy per fraction, 

for a total dose of 60 Gy. Concomitant chemotherapy consisted of TMZ 

at a dose of 75 mg/m 2 . After a 4-week break, patients were then to receive 

12 cycles of 1 week on/1week off TMZ, with 75 mg/m 2 the first cycle, 100 

mg/m 2 the second one, 125 mg/m 2 the third one, 150 mg/m 2 from the fourth 

to the twelfth one. Haematological toxicity was monitored every week during 

concomitant chemo-radiotherapy and every 4 weeks after. Statistical analysis 

was performed with Intercooled Stata 9.2. 

Results: Follow-up ranged from 8 to 27 months (median 10 months). Among 

RPA class 4 patients (age50, KPS

S 220 CLINICAL/DISEASE SITES : GASTROINTESTINAL TUMORS 

26 mts vs 6 mts in IELSG score 3-4 (p < 0.05); median OS in patients with 

IELSG score 1-2 was 32 mts vs 12 mts in IELSG score 3-4 s (p < 0.05). 

Conclusions: Our data confirmed prognostic value of IELSG score on DFS 

and OS; therefore we need perspective trials to test its utility on therapeutic 

strategy. 

Clinical/Disease sites : Gastrointestinal 

tumors 

675 poster 

SHORT-COURSE PRE-OPERATIVE RADIOTHERAPY WITH ELEC- 

TIVE DELAY PRIOR TO SURGERY, IN FRAIL AND POOR PS 

PATIENTS WITH UNRESECTABLE RECTAL CANCER. 

D. Sebag-Montefiore 1 , M. Hingorani 1 , G. Radhakrishna 1 , P. Hatfield 1 , R. 

Cooper 1 , A. Melcher 1 , A. Crellin 1 

1 ST. JAMES INSTITUTE OF ONCOLOGY, Clinical Oncology, Leeds, United 

Kingdom 

Purpose: Neoadjuvant CRT is regarded as standard treatment for patients 

with unresectable rectal cancer. However, it is not always feasible to treat 

patients with CRT because of frailty, poor performance status or medical comorbidity. 

Short course radiotherapy [SCPRT] using 25 Gy in 5 fractions is 

a highly effective radiotherapy schedule and may result in downstaging if a 

6-8 week interval is allowed for tumour regression prior to surgery (delay- 

SCPRT). We report on the early outcome measures observed in a cohort of 

patients, treated in our centre using delay-SCPRT, with locally unresectable 

disease. 

Materials: Forty-three patients, treated between 2000 and 2007, were retrospectively 

identified. All patients had either clinically fixed tumours or MRIscan 

evidence of tumour within 2mm of the radial resection margin (CRM). 

Data includes patient demographics, relevant co-morbidities, tumour characteristics 

and details of any post-RT radiological assessment. In addition, the 

surgical, pathological, and clinical outcome (local recurrence [LR] and overall 

survival [OS]) were evaluated. 

Results: The mean age of patients was 80 years (range 58-87) with 22 

(51.2%) male and 21 (48.8%) female. The primary indication for delay- 

SCPRT was frailty or a poor PS of ≥ 2 in 32 (74.4%), and associated comorbidities 

in 11 (25.6%) patients. The proportion of low, mid, and high tumours 

was 42%, 40%, and 18% respectively. 26/43 (60.5%) patients proceeded 

to surgery at median interval of 8 weeks after delay-SCPRT. 22/26 

(85%) underwent resection with an uninvolved CRM, 2/26 (7.5%) had CRM 

involvement (defined as tumour T3 or >N1, 

aged between 18-80, ECOG ≤ 2, adequate bone marrow reserve, and normal 

renal and hepatic functions were included. Pre-treatment staging was 

performed with magnetic resonance or endorectal ultrasound. Patients were 

treated with oral capecitabine 825 mg/m2/12 h days 1 to 42 continuously, 

and 50 Gy RT in 2 Gy fractions. Three-dimensional planning and conformal 

techniques were used in all patients. 

Results: Thirty patients were enrolled (M/F 22/8), median age 63.3 years 

(33-80) and ECOG =0: 85.1%. Tumor was located within the 5 distal cm in 

21 patients (70%) and between 6 and 15 cm from the anal verge in 9 patients 

(30%). Fifteen patients (50%) were T3N0M0, 12 (40%) T3N1-2M0 

and 3 (10%) T2N1-2. Twenty-seven patients (90%) completed combined 

modality therapy, three patients completed RT but not chemotherapy. The 

most frequent treatment-related grade I/II toxicities were diarrhea (40%), frequency/dysuria 

(16%), proctitis (26%), hand-foot syndrome (6%) and leucopenia 

(4.5%). Grade III toxicities were limited to diarrhea (2 patients) and 

hand-foot syndrome (1 patient). An anterior resection was performed on 17 

patients (56%), an abdominal-perineal resection in 10 (33%) and a transanal 

resection in 3 patients (10%). There were no major postoperative complications. 

Nine patients (30%) had pathologic complete response, 14 (46%) 

had partial response and 7 (23%) had stable disease. Table 1 shows the 

downstaging of the disease. 

Conclusions: The combination of preoperative capecitabine and RT in patients 

with locally advanced rectal cancer has significant antitumor activity, 

with a high proportion of complete pathological responses and tumour downstaging. 

The sphincter preservation rate was high, and the toxicity profile was 

acceptable in these patients. 

677 poster 

ABDOMINAL CRAMPS AS A SIGN OF EARLY POSTRADIATION 

REACTION DURING PREOPERATIVE RADIOCHEMOTHERAPY FOR 

RECTAL CANCER 

A. Rychter 1 , J. Fijuth 1 , M. Spych 1 

1 COPERNICUS MEMORIAL HOSPITAL, REGIONAL CANCER CENTRE, 

Radiation Oncology, Lodz, Poland 

Purpose: Abdominal pain manifested as cramps may be one of the most 

distressful symptoms experienced by patients during the rectal cancer radiochemotherapy. 

Causes of these symptoms are complex and still not clear. 

They may not be associated with diarrhea and interfere with protocol compliance. 

The aim of this work is to investigate the clinical and dosimetric factors 

influencing occurrence and intensity of abdominal cramps among patients receiving 

radiochemotherapy for locally advanced rectal cancer 

Materials: Fifty consecutive patients with locally advanced rectal cancer 

treated with radiochemotherapy at Copernicus Memorial Hospital were under 

evaluation. The doses of radiotherapy of 50 Gy52,2 Gy in fractions of 

1,8 Gy to 2 Gy were applied. The chemotherapy regimen consisted of 350 

mg/m 5-Fu and 20mg/m of Leucovorin given for five days during the first and 

last week of radiotherapy. Presence of symptoms had being assessed every 

week according to own adopted scale based on RTOG/EORTC toxicity 

score. The endpoint for this analysis was the occurrence of Grade 3 abdominal 

cramps (requiring opioids and treatment breaks) according to own toxicity 

score. The statistical analyses were performed to determinate risk factors 

of abdominal pain occurrence. Patient characteristic clinical factors such as: 

age, pre-treatment haemoglobin level, bladder volume, diet compliance and 

alcohol use during radiotherapy treatment were included to statistical analysis. 

Following parameters related to radiotherapy technique were included to 

statistical analysis: volumes of intestine receiving doses between 5 Gy and 50 

Gy(V5-V50), median and maximum PTV dose and maximum intestine doses. 

Results: Nineteen (38%) patients developed mild and intensive abdominal 

cramps classified as degree of 211 (22%) and 3-8 (16%) according to our 

score. In 52 % of cases they were not connected with diarrhoea. Analysis 

of clinical factors revealed the trend of young age, low pre-treatment Hb level 

and female sex towards intensity of symptoms (respectively p=0,06, p=0,06, 

p=0,057). Among the dosimetric factors the most important: were volumes of 

bowel included within the isodoses of 40 and 45 Gy (p=0.016, p=0,001). 

Conclusions: None of clinical factors influenced occurrence of abdominal 

cramps. The dosimetric parameters influencing occurrence of this symptom 

were volumes of bowel inside high dose - 40-45 Gy isodoses. The volume 

of bowel within doses above 40 Gy should be reduced to improve safety and 

tolerance of radiochemotherapy of rectal cancer.

678 poster 

ADJUVANT CHEMORADIATION OF PANCREATIC CANCER - 

EFFECTIVENES AND TOLERANCE OF COMBINED THERAPY 

A. Namysl-Kaletka 1 , L. Miszczyk 1 , A. Idasiak 1 , E. Wolny 1 , G. Wozniak 1 , 

J. Wydmanski 1 

1 CENTRE OF ONCOLOGY MSC MEMORIAL INSTITUTE GLIWICE, Radiother- 

apy Department, Gliwice, Poland 

Purpose: An evaluation of the results and toxicity of radiotherapy combined 

with chemotherapy for postoperative pancreatic cancer patients. 

Materials: Retrospective analysis of treatment results 35 of patients with pancreatic 

cancer after surgery was performed. Mean patients age was 58. All 

were in good performance status. The most common tumor type was adenocarcinoma. 

Majority of patients had locally advanced disease (T3), 42% 

pts were nodal positive. Tumor size ranged from 1,5 to 4 cm. Patients were 

treated with high energy photons to total dose of 45-50,4 Gy delivered in 1,8 

Gy fraction dose. Mean CTV volume was 180 ccm. In all cases radiotherapy 

was combined with CT. Chemotherapy was based on 5-fluorouracyl and 

leucovorin. Mean follow up was 12 months. LC, DFS, and distant metastases 

rate were evaluated. Gastrointestinal and hematological toxicity were 

assessed. Correlations between parameters were tested using Sperman 

analysis, survival analysis was done using Kaplan Maier method. 

Results: Overall survival was 42% and DFS was 56%. Metastases were observed 

in 10 cases, the most commonly in liver. The mean period to mets 

detection was 10 months. Local relapse were found in 3 cases. Gastrointestinal 

and hematological tolerance was acceptable. Spearman analysis did not 

revealed any significant correlation between parameters. Kaplan Maier analysis 

did not show statistical significant survival differences between T and N 

status patients. Also neither grading nor surgical margin status did not influence 

on DFS. 

Conclusions: Obtained results allow to form conclusions that well performed 

surgery remains mainstay therapy and fundamental prognostic factor of pancreatic 

cancer. Adjuvant radiochemotherapy is moderately effective and well 

tolerated treatment for pancreatic cancer patients. 

679 poster 

ADJUVANT CHEMORADIOTHERAPY AFTER CURATIVE RESEC- 

TION FOR EXTRAHEPATIC BILE DUCT CANCER 

K. Kim 1 , E. K. Chie 1 , S. W. Kim 2 , Y. J. Bang 3 , S. W. Ha 1 

1 

SEOUL NATIONAL UNIVERSITY COLLEGE OF MEDICINE, Radiation 

Oncology, Seoul , Korea Republic of 

2 

SEOUL NATIONAL UNIVERSITY COLLEGE OF MEDICINE, Surgery, Seoul , 


3 

SEOUL NATIONAL UNIVERSITY COLLEGE OF MEDICINE, Department of 

Internal Medicine, Seoul , Korea Republic of 

Purpose: To analyze the outcome of adjuvant chemoradiotherapy for patients 

with extrahepatic bile duct (EHBD) cancer who had undergone curative 

surgery, and to identify the prognostic factors for these patients. 

Materials: Between January 1995 and December 2002, 86 patients with adenocarcinoma 

of the EHBD underwent curative resection followed by adjuvant 

chemoradiotherapy. There were 59 males and 27 females, and median age 

was 59 years (range; 34-73). Postoperative radiotherapy was delivered to tumor 

bed and regional lymph nodes up to 40 Gy at 2 Gy per fraction with a twoweek 

planned rest. Intravenous 5-fluorouracil (500mg/m2/day) was given on 

day 1 to 3 of each split course. The median follow-up period was 33 months 

in all patients, and was 83 months in survivors. 

Results: The 5-year overall survival rate of all patients was 44.7%, with a median 

survival time of 34 months. On univariate analysis, number of involved 

lymph node ≥3 and poorly-differentiated tumor were associated with poor 

overall survival. There were no differences of 5-year overall survival rates between 

patients with R0-resected tumors and R1-resected ones (46.3% and 

41.4%, respectively, p = 0.6641). When age (≤60 vs. >60 yrs), extent of 

resection (R0 vs. R1), tumor location (proximal vs. distal), T stage (T1-3 vs. 

T4), number of involved lymph node (0-2 vs. ≥3), histologic differentiation 

(well- and moderately-differentiated vs. poorly-differentiated), and the interval 

between surgery and radiotherapy (3 positive nodes, RR: 2.9, 

95% CI: 1.15-7.3, p=0.02) were related significantly to relapse-free survival. 

The lymph node status influenced significantly the disease-specific survival 

too (RR: 3.35, 95% CI: 1.15-9.76, p=0.03). The reviewed studies confirmed 

the INT 0116 trial’s survival outcomes. In these articles the median follow-up 

time varied between 20 and 66 months and the three year overall survival 

rate between 54% and 69%. In six studies they treated the patients with microscopic 

residual tumor also and evaluated the outcome. Positive surgical 

margins had negative impact on disease-free survival in five of the reviewed 

trials. Toxicity was observed in a lower percentage in every article (GI: 14- 

33%, HAE: 9.7-34%) than in the INT 0116 trial (GI: 33%, HAE: 54%). The 

rate of toxic death was higher only in one study (10.5%) and was less than 

2% in the rest. 

Conclusions: Our and the published survival results are similar to the INT 

0116 trial’s outcome, but grade 3-4 toxicity was observed in lower percentage. 

In more than half of the studies the protocol was also applied in patients with 

R1 resection. R1 status has negative impact on survival. In these cases 

more aggressive chemotherapy may improve the results. For the protocol’s 

final evaluation more patients and longer follow-up time are needed. 

681 poster 

ADJUVANT CONCURRENT CHEMORADIOTHERAPY IS ABLE TO 

IMPROVE SURVIVAL AND LOCAL-REGIONAL CONTROL FOR 

RECTAL CANCER PATIENTS WITH MODERATELY HIGH-RISK 

J. Jin 1 , Y. Li 1 , N. Li 1 , X. Chen 1 , T. Li 1 , S. Wang 1 , W. Wang 1 , Y. Liu 1 , Y. 

Song 1 , X. Liu 1 , Z. Yu 1 

1 CANCER HOSPITAL, CHINESE ACADEMY OF MEDICAL SCIENCES, 

Radiation Oncology, Beijing, China 

Purpose: To analyze the survival and relapse rates by T and N stage and 

choose the proper adjuvant therapy for rectal cancer patients with different 

risk. 

Materials: Data were pooled between January 2000 and December 2004, 

669 patients with stage II (48.1%) and III rectal carcinoma after radical 

resection [Low abdomen resection (LAR), 69.2%; Anterior perineal resection 

(APR), 30.8%] were retrospectively reviewed. Surgery (S) was the 

only treatment in 105 patients (15.7%), while others received adjuvant 

treatment as follows: irradiation (RT) with or without chemotherapy (CT; 

n=174), concurrent chemoradiothrapy (CRT) with or without CT (n=321), CT 

alone (n=38) and unknown (n=31). The 95.7% of RT dose to the pelvic 

was between DT 45-50.4Gy. Most concurrent chemotherapy agents were 

oral 5-fluorouracil (5-FU; 90.0%, 289/321) including Carmofur (185/289), 

capecitabine (34/289), doxifluridine (56/289) and Tegufer (14/289). Regimen 

for CT were oxaliplatin/5-FU/leucovorin (CF; 131/292, 44.8%), hydroxycamptothecin 

(HCPT)/5-FU/CF（92/292, 32.6%）and 5- 

FU/CF(66/292，22.6%). The median follow-up was 3.4 year, and 

90.7% of patients were available at the end of last follow-up of Dec. 31, 

2006. 

Results: The 5-year overall survival (OS), relapse-free survival (RFS), causespecific 

survival (CSS), local-regional relapse free survival (LRFS) and distant 

metastasis free survival (DMFS) for whole group were 69.6%, 64.4%, 

73.2%, 85.9% and 75.7%, respectively. Patients were grouped based on 

OS rate: (1) intermediate (IIA and IIIA, n=312, 46.6%), with 5-year OS 

rate above 80%, (2) moderately high (IIB, IIIB, IIIC except T4N2, n=322, 

48.1%) with 50-80% and (3) high (T4N2, n=35, 5.2%), lower than 50%.The


5-year OS, RFS, CSS, LRFS and DMFS rates for three groups were 80.3%, 

63.2%, 30.8% (P=0.000); 78.2%, 55.1%, 22.7% (P=0.000); 85.2%, 66.0%, 

30.8% (P=0.000); 91.0%, 82.1%, 65.8% (P=0.001); and 86.8%, 68.3, 40.8% 

(P=0.000). Adjuvant therapy (RT or CRT ± CT, n=533) could definitely improve 

OS, RFS, LRFS when compared with S alone (n=105) (72.5% vs 

56.6%, P=0.000; 66.3% vs 55.9%, P=0.048; 87.6% vs 76.5%, P=0.015), 

but mainly benefited for moderately high-risk group (adjuvant therapy group, 

n=226 vs. S alone, n=37; 65.4% vs 53.6%, P=0.007; 58.3% vs 36.6%, 

P=0.028;85.7% vs 55.2%, P=0.000), not for intermediate or high-risk groups. 

When comparing RT±CT (n=86) and CRT±CT (n=161) further in moderately 

high-risk group, CRT±CT significantly improved OS, RFS, CSS, and 

LRFS (73.8% vs 54.0%, P=0.01; 64.1% vs 47.9%, P=0.02; 76.7% vs. 55.9%, 

P=0.007; and 89.6% vs 73.9%, P=0.033). 

Conclusions: Adjuvant therapy can improve long-term survival and localregional 

control for stage II and III rectal cancer, mainly benefit for patients 

with moderately high-risk, especially when employed with concurrent 

chemoradiothreapy. Different treatment strategies may be indicated differently 

for intermediate-risk versus moderately high- or high-risk patients. 

682 poster 

ADJUVANT RADIOTHERAPY (RT) FOR EXTRAHEPATIC BILE 

DUCT CANCERS (EBDC): THE GENEVA UNIVERSITY HOSPITALS 

EXPERIENCE 

M. Bonet Beltran 1 , A. D. Roth 2 , G. Mentha 3 , A. S. Allal 4 

1 

HOSPITAL SANT JOAN DE REUS AND GENEVA UNIVERSITY HOSPITALS, 

Radiation Oncology, Reus-Tarragona, Spain 

2 

GENEVA UNIVERSITY HOSPITALS, Oncosurgery, Geneva, Switzerland 

3 

GENEVA UNIVERSITY HOSPITALS, Unit of Visceral and Transplantation 

Surgery, Geneva, Switzerland 

4 

GENEVA UNIVERSITY HOSPITALS, Radiation Oncology, Geneva, Switzer- 

land 

Purpose: EBDC are uncommon malignancies and have poor prognosis with 

high rates of locoregional recurrence. The role of adjuvant RT remains unclear. 

The purpose of the present study is to assess the feasibility and the 

potential impact of adjuvant RT in a series of patients treated in one institution. 

Materials: Between 1998 and 2004, 38 patients with non-metastatic bile duct 

cancer received RT. We excluded 12 patients presenting with unresectable 

disease and 3 with intrahepatic cholangiocarcinoma. The remaining 23 patients 

treated with surgery with curative intent were evaluated. Four patients 

had gallbladder cancer, 12 cholangiocarcinoma and 7 ampullary cancers. 

Surgical margins were negative in 11 (48%), narrow in 2 (9%), and microscopically 

involved in 8 (35%). Eleven patients (55%) had pathological nodal 

involvement. All patients received 3D-CRT to a median total dose of 50.4 Gy. 

In only one patient, a 20 Gy brachytherapy boost was delivered due to gross 

positive margins. The majority of patients received concurrent chemotherapy 

based on 5-FU. Median follow-up for all patients was 31 months (range 4-79), 

with a minimal follow-up for surviving patients of 56 months (range 39-78). 

Results: All patients completed the planned RT schedule without interruption. 

Acute grade 2 (RTOG) abdominal pain and diarrhea was recorded in 2 

patients (9%). Nausea or vomiting grade 1 and 2 was observed in 8 (35%) 

and 2 patients (9%) respectively. One patient developed a major late toxicity 

potentially RT-related at 11 months post treatment (surgical anastomosis 

stenosis requiring a partial gastrectomy). At last evaluation 7 patients were 

alive. The main pattern of recurrence was both locorregional and distant (liver, 

peritoneum and/or lung). No difference was observed in locorregional control 

according to the tumor sublocation. The 5-year actuarial loco-regional control 

rate was of 61.8% (78% and 48% for patients operated on with negative and 

positive/narrow/unknown margins respectively, p=0.15). The 5-year actuarial 

overall survival was of 29.6% for the entire group (55% if negative margins 

and 16.7% if positive/narrow/unknown margins, p=0.18). 

Conclusions: Postoperative radiotherapy with 50-60 Gy is feasible with acceptable 

acute and late toxicities. While patients with positive surgical margins 

had a lower loco-regional control, some patients seem to have beneficed 

from adjuvant treatment. Prospective randomized trial is needed to confirm 

definitively the role of RT in this tumor location. 

683 poster 

ADJUVANT THERAPY RADIOTHERAPY-BASED ON OLDER AND 

OLDEST ELDERLY RECTAL CANCER PATIENTS 

F. Fiorica 1 , F. Cartei 1 , S. Ursino 1 , M. Berretta 2 , S. Berretta 3 

1 UNIVERSITY HOSPITAL S’ANNA, Radiotherapy, Ferrara, Italy 

2 NATIONAL CANCER INSTITUTE, CRO, Medical Oncology, Aviano, Italy 

3 UNIVERSITY OF CATANIA, Surgery, Catania, Italy 

Purpose: The pupose of this study was to evaluate the impact of radiotherapy 

in terms of feasibility and activity in patients aged ≥ 75 with advanced rectal 

cancer. 

Materials: From January 2002 to December 2006, 41 consecutive patients 

(27 men and 14 women) aged ≥ 75 received radiotherapy for local advanced 

rectal cancer, 9 in a pre-operative and 22 in a post-operative setting. Sixteen 

patients received concomitant chemotherapy. Variables considered were age, 

co-morbidities (evaluated according to the Adult Co-morbidity Evaluation index 

ACE-27), surgery versus no surgery, and timing of radiotherapy. 

Results: The median age was 80.5 years (range 75-90). A total of 19.5% 

patients had no co-morbidity, 48.8% mild, 17.1% moderate and 14.6% severe 

co-morbidities. Thirty-nine subjects (95.1%) were submitted to surgery. All 

patients but one completed the planned radiation schedule. At median followup 

of 23.1 months, the 2- and 4-year overall survival rates were 71.8% and 

61.6%, respectively. There was a better survival for patients with no or mild 

co-morbidities (p= 0.002) and a good performance status (p=0.003). The 

cancer-free survival at 2- and 4-years was 78.9% and 26.4%, respectively. 

No difference in acute and late toxicity rates was found between patients with 

different ACE-27 indexes. 

Conclusions: Compliance with radiotherapy is good and rate of toxicity is acceptable 

in elderly patients. Patients with no or mild co-morbidities have a significantly 

better survival. Increasing severity of co-morbidity may sufficiently 

shorten remaining life expectancy to cancel gains with adjuvant radiotherapy. 

Further prospective trials are needed to confirm these results. 

684 poster 

AN IMPROVED DRINKING PROTOCOL TO DECREASE IRRADIATED 

VOLUME OF SMALL BOWEL DURING RADIOTHERAPY OF RECTAL 

CANCER 

M. Eenink 1 , W. Heemsbergen 1 , B. Doodeman 1 , R. de Jong 1 , C. Marijnen 

1 , C. van Vliet-Vroegindeweij 1 

1 NETHERLANDS CANCER INSTITUTE - ANTONI VAN LEEUWENHOEK 


Purpose: Small bowel complications are the major adverse side effect associated 

with radiotherapy of rectal cancer. The amount of irradiated small 

bowel can potentially be reduced by treating patients with a full bladder. The 

aim of this study was to evaluate a new drinking protocol that was recently 

introduced in our clinic to this end. 

Materials: Old protocol (OP): patients were instructed to empty their bladder 

one hour before start of treatment and subsequently drink 250 ml of water. 

New protocol (NP): patients were instructed to void one hour before start of 

treatment and drink 350 ml / 500 ml of water. In addition, with the aim of reducing 

day-to-day variability in bladder filling, patients were instructed to drink 

2 liters of fluids (with the exception of alcoholic beverages and coffee) per day 

during the course of treatment. Patients with early stage rectal cancer were 

considered, receiving radiotherapy (5x5 Gy) prior to surgery. The bladder was 

delineated on the planning CT and on cone-beam CT (CBCT) images, which 

were acquired for each fraction. 

Results: So far, 28 patients under OP and 13 patients under NP were considered 

for analysis. The first 4 patients under NP received 500 ml and were 

excluded from further analyses: 2 of these patients had trouble maintaining a 

full bladder. The subsequent 9 patients were therefore asked to drink 350 ml, 

which was well tolerated. Bladder volume during treatment, obtained from the 

CBCT images, was 189 ± 116 ml (mean ± SD) for OP and 272 ± 126 ml for 

NP (p=0.046). The number of times bladder volume on CBCT deviated more 

than 50 ml and 100 ml from planning CT was increased with NP (respectively 

p=0.005 and p=0.03, chi-squared trend test). However, the relative deviation 

of CBCT bladder volume from planning CT did not differ significantly between 

OP and NP. 

Conclusions: With the new drinking protocol, bladder volume during treatment 

is increased. The new protocol results in an absolute, but not relative, 

increase of inter-fraction variability in bladder volume. No evidence was 

found for effects associated with the additional drinking instruction. A complete 

assessment of the new protocol needs to take into account the effect of 

the increased bladder variability on required PTV margins and corresponding 

modification of IMRT technique. These studies are currently under way. 

685 poster 

ANAL CANCER "SHOULD A MAINTENANCE CHEMOTHERAPY 

AFTER INITIAL (CHEMO)RADIOTHERAPY BE CONSIDERED" 

(ANALYSIS OF 20 YEARS RESULTS.) 

P. Vitek 1 , J. Kubes 1 , J. Dvorak 1 , F. Trebicky 1 

1 INSTITUTE OF RADIATION ONCOLOGY, University Hospital Na Bulovce, 

Praha 8, Czech Republic 

Purpose: Anal canal cancer is efficiently treated by chemoradiotherapy 

achieving high rate of complete regression. On the other hand the survival 

data do not reflect this high efficacy in general and the prognosis was even 

quoted as "poor". The relationship between good efficacy and limited survival 

reflects either high relapse rate or substantial toxicity. The U.K. phase III trial 

ACT II addresses the question of maintenance chemotherapy, however the 

mature data are not yet available. A single institution retrospective analysis 

was performed to assess survival data after completed chemoradiation and 

to evaluate the influence of either relapse or toxicity. 

Materials: 62 patients with epidermoid cancer of anal canal, clinical stage

I IIIB underwent chemoradiotherapy or radiotherapy alone in a period from 

1986 to 2006. Median age at diagnosis was 57 years (25-84). 2 pts. were 

HIV positive. The administered dose was 54 -60 Gy and 70 Gy for chemoradiation 

or radiation alone respectively. Elective radiation of iliac nodes was 

included. Common chemotherapy regimen mitomycin C (d 1) + continuous 

5-fluorouracil (d 1-4, 29-32) was employed. There was no further treatment in 

pts. achieving complete regression. Patients in partial regression underwent 

abdominoperineal resection. 

Results: Complete regression and partial regression rates were 89% and 

10% respectively. Upon analysis 44 pts. (71%) are alive, 18 pts. (29%) died. 

The overall survival data (median 80 months, 5 year 65%) contrast with overall 

relapse rate 24% (median time to relapse 11 months). 4 pts. (6,5%) died 

in relationship to principal disease. The acute toxicity gr. III, IV RTOG (mucositis, 

dermatitis, leukopenia) and late effects (fibrosis, strictures, atrophy, 

sphincter failures, mucosal ulcerations, osteoradionecrosis) were reported in 

24 pts. (38%) and 13 pts. (21%) respectively. 5 pts. (8%) did not complete 

the treatment due to excessive toxicity. 2 toxic deaths were reported (renal 

failure, bowel perforation). 

Conclusions: Chemoradiation (evtl. radiation alone) is an effective frontline 

treatment for the epidermoid anal cancer. On the other hand the toxicity, 

including long term effects, is substantial. The survival data presented are 

favorable. If a maintenance chemotherapy is considered, it remains questionable 

how far it may contribute to toxicity or reduce relapse rate and how far 

the overall survival may be impacted. 

686 poster 

BOOSTING ANAL SQUAMOUS CELL CARCINOMA WITH HELICAL 

TOMOTHERAPY 

A. Roegiers 1 , C. Clermont 1 , F. Alexis 2 , J. F. Daisne 1 

1 

CLINIQUE & MATERNITÉ STE-ELISABETH, Radiation Oncology, Namur, 

Belgium 

2 

CLINIQUE & MATERNITÉ STE-ELISABETH, Radiology, Namur, Belgium 

Purpose: Boosting anal squamous cell carcinoma (SCC) can usually be performed 

either with brachytherapy or external beam radiotherapy. For patients 

with non-circonferential tumors, we present an original approach combining 

highly conformal radiotherapy with daily image guidance through the use of 

a helical tomotherapy unit. The aim is to preserve as much normal sphincter 

as possible and ultimately preserve satisfactory anal function in the frame of 

organ preservation treatment with high dose radiotherapy. 

Materials: Three patients (two females and one male) aged 39, 41 and 

55 at diagnosis of locally advanced (respectively T2N3M0, T4N0M0 and 

T3N0M0) anal SCC were treated with curative intent with combined radioand 

chemotherapy. Prophylactic radiotherapy was administered to the whole 

pelvis to a dose of 45 Gy (1.8 Gy by fraction) with a sliding window IMRT 

technique delivered by a classical LINAC unit. One week before the end of 

this first phase, patients underwent a new planning CT in prone position with 

a plastic tube inserted in the anal canal. Boost volume was defined in the 

male patient with submucosal metallic fiducials inserted pre-treatment and in 

the two female patients with diagnostic MRI matched to the CT. A dose of 20 

Gy (2.0 Gy by fraction) was delivered without planned split course with helical 

tomotherapy. After insertion of plastic tube, daily MV-CT was performed and 

matching to planning CT was done with special attention to plastic tube and 

pathologic nodes when indicated. Response was evaluated at three months 

with rectoscopy, PET-CT and MRI. Follow-up was performed clinically with a 

special emphasis on perineal functions. 

Results: All patients completed treatment without planned break. At followup 

times of 15, nine and five months, all are disease-free. One patient experienced 

minor and inconstant anal incontinency without significant impact on 

social life, the two others presenting satisfactory anal function. Male patient 

experienced worsening of a pre-existant penile dysfunction and both women 

presented dyspareunia due to mild shrinkening of the introitus. One patient 

presented significant dysuria requesting the prescription of oxybutinine. All 

three patients were though globally satisfied of the functional result. 

Conclusions: Boosting anal SCC with helical tomotherapy is feasible and 

offers the possibility to administer high dose radiotherapy while minimizing 

the functional impact of treatment. 

687 poster 

CHANGES IN 18-FDG PET MYOCARDIAL ACTIVITY AFTER 

CHEMORADIOTHERAPY FOR ESOPHAGEAL CANCER MAY NOT 

PREDICT FOR SYMPTOMATIC CARDIAC TOXICITY 

A. Konski 1 , T. Li 2 , J. Cheng 3 , J. Yu 4 , N. Meropol 3 , S. Cohen 3 , W. Scott 

5 , N. Lewis 3 , G. Freedman 1 

1 FOX CHASE CANCER CENTER, Radiation Oncology, Philadelphia, USA 

2 FOX CHASE CANCER CENTER, Biostatistics, Philadelphia, USA 

3 FOX CHASE CANCER CENTER, Medical Oncology, Philadelphia, USA 

4 FOX CHASE CANCER CENTER, Diagnostic Imaging, Philadelphia, USA 

5 FOX CHASE CANCER CENTER, Surgical Oncology, Philadelphia, USA 

Purpose: The purpose of this study was to determine if changes in myocar- 

CLINICAL/DISEASE SITES : GASTROINTESTINAL TUMORS 

S 223 

dial uptake of 18-FDG PET correlate with symptomatic cardiac toxicity in patients 

with esophageal cancer treated with combined modality local therapy. 

Materials: Eighty-six patients with locally advanced esophageal cancer between 

6/02 and 11/06 presented for treatment. Twenty-six patients only had 

1 PET scan and 7 did not have complete DVH analysis of treatment and were 

ineligible for analysis. 53 eligible patients with locally advanced esophageal 

carcinoma undergoing pre-operative or definitive chemoradiotherapy (CRT) 

had pre- and post-treatment 18-FDG PET scans with % change in maximum 

SUV measured from the septum, apex and lateral wall of the heart. Cardiac 

toxicity as measured by RTOG and Common Toxicity Criteria Adverse 

Events (CTCAE) v3.0 was identified by retrospective chart review. Wilcoxan 

test was used to determine an association between the % SUV change and 

factors of: any cardiac toxicity, RTOG or CTCAE v3.0 cardiac toxicity, sex, 

prior heart disease, diabetes, insulin use, smoking history or prior cardiac 

bypass/angioplasty. The Spearman correlation was used to determine association 

of Heart V(20, 30, 40), Left Ventricle V(20, 30, 40) days from RT 

completion and post-treatment PET, and age. 

Results: The median % change was -18 (range: -90-362)%, -9 (range: -84- 

455)%, and -6 (-88-1110)% for the lateral wall, septum and apex respectively. 

The median days between end of RT and PET scan was 25 (range: 10-76) 

days. Median follow-up was 16 (range: 4-56) months. Eleven patients were 

identified as having a cardiac toxicity ([RTOG grade 3- 8 and RTOG grade 

4- 3] and [CTCAE grade 1- 3 and 4- 6, 4 and 1 respectively). There was no 

correlation with the investigated variables and incidence of cardiac toxicity. 

Conclusions: In this pilot study and first of it’s kind, we have not identified 

a correlation between percent change in SUV myocardial uptake and cardiac 

toxicity. Further study with more patients should be performed to confirm 

these preliminary data. 

688 poster 

COMPARISON OF CHEMOTHERAPY REGIMEN IN PRE-OPERATIVE 

CHEMORADIATION FOR RECTAL CANCER 

H. J. Park 1 , J. Lee 1 , E. K. Chie 1 

1 SEOUL NATIONAL UNIVERSITY HOSPITAL, Radiation Oncology, Seoul, 


Purpose: To examine the relationship between chemotherapy regimen and 

outcome and factors affecting tumor response in patients with rectal cancer 

who underwent preoperative chemoradiotherapy. 

Materials: Medical records of 103 patients who received preoperative 

chemoradiotherapy followed by radical surgery for clinical staged T3 or 4 rectal 

cancer from July 2003 to November 2007 were retrospectively reviewed. 

Radiation dose ranged from 50.4 Gy to 54 Gy. Thirty patients were treated 

with one cycle of bolus 5-FU (group A), 56 with two cycles of bolus 5-FU 

(group B) and 17 with oral Capecitabine (group C). Interval from radiotherapy 

to surgery was 37 to 80 days (median 57). Ninety one patients underwent 

low anterior resection, while three patients underwent Hartmann’s operation 

and another nine underwent abdominoperineal resection. 

Results: The complete pathologic response and overall downstaging rate 

were 12.6% and 71.8%, respectively. The pathologic response rate of grade 

3 to 5 and downstaging rate for group A, group B, and group C were 

67.6%/66.7%, 77.3%/75% and 80%/68.1%, respectively. The rate of sphincter 

saving surgery was higher in group B compared to group A in low lying 

tumor (97.4% vs. 75 %, p = 0.007). Pathologic response rate had correlation 

with overall downstaging. There was no statistically significant difference in 

pathologic response rate, overall downstaging and sufficient (> 0.5cm) radial 

resection margin between three groups. The pathological response rate of 

grade 3 to 5 was significantly higher in female patients (89.3% vs. 66.7%, p 

= 0.021) and patients with longer interval (> 58 days) between radiotherapy 

to surgery (82% vs. 64.2%, p = 0.049). There was no grade 3 to 4 gastrointestinal 

or hematologic toxicity during treatment in all patients. 

Conclusions: Different chemotherapy regimen had no impact on significant 

pathologic response, downstaging and sufficient radial resection margin 

in cT3-4 rectal cancer with preoperative chemoradiation therapy. However, 

sphincter salvage rate in low lying tumor was significantly lower in insufficient 

chemotherapy regimen group without difference in grade 3 or higher toxicity. 

Based on this result, patient should be offered sufficient chemotherapy in 

combination with radiotherapy to maximize the chance of sphincter preservation. 

689 poster 

CONTACT X-RAY TREATMENT FOR RECTAL CANCER. EARLY 

EXPERIENCE IN CENTRE ANTOINE LACASSAGNE (CAL) 

K. Benezery 1 , J. P. Gerard 1 , A. Ginot 1 , E. Francois 2 , J. M. Hannoun-Levi 

1 , S. Marcié 3 

1 CENTRE ANTOINE LACASSAGNE, Radiation Oncology, Nice, France 

2 CENTRE ANTOINE LACASSAGNE, Medical Oncology, Nice, France 

3 CENTRE ANTOINE LACASSAGNE, Medical Physics, Nice, France 

Purpose: Contact x-ray (CXR) was used in CAL since 2002 for rectal cancer 

for curative and conservative intent.


Materials: Between 2002 and 2006, 44 patients (pts) were treated in four 

different clinical situations : 1) T1 N0 tumors treated with Transanal Local 

Excision (TLE) followed by adjuvant CXR (45 Gy/3 F) (7 pts). 2) T2-3 M0 

tumors in inoperable pts (11) treated with combined CXR (90-100 Gy/3-4 F) + 

External Beam Radiotherapy (EBRT) + concurrent chemotherapy. 3) T3 N0-2 

tumors treated with preoperative CXR (70-10 Gy/3-4 F) + EBRT (+ concurrent 

chemotherapy) followed by surgery (21 pts). 4) : T2 tumors treated with CXR 

(70-10 Gy/3-4 F) + EBRT followed by TLE (5 pts). 

Results: Median follow up was 25 months. 1) Local excision first : no local 

failure was observed. Anorectal function was good in all cases. 2) CXR 

+ EBRT alone :out of 11 patients, 10 were locally controlled with a good 

anorectal function. 3) Preoperative CXR + EBRT : anterior resection was 

performed in 16/21 patients. Complete sterilization of the operative specimen 

was seen in 4 cases (19%). No local recurrence occurred so far. 4) In 5 

patients treated with CXR + EBRT + TLE a complete or near complete clinical 

response was observed in all cases. A TLE with R0 resection margin was 

performed in all cases. Rectum was preserved with a good function in all 

these patients. 

Conclusions: These early results confirm that CXR in association with 

surgery (or alone with EBRT) is playing a major role in the conservative and 

curative treatment of rectal cancer. This technique should see a strong renewal 

with the manufacturing in 2008 of a new contact x-ray unit (Papillon 

50). 

690 poster 

CYBERKNIFE (CK) STEREOTACTIC RADIOTHER- 

APY/RADIOSURGERY IN THE TREATMENT OF PATIENTS 

(PTS) AFFECTED WITH PANCREATIC MALIGNANT NEOPLASM. 

M. Possanzini 1 , L. C. Bianchi 1 , L. Brait 2 , A. Bergantin 2 , F. Locatelli 2 , M. 

Meregalli 3 , A. Brambilla 3 , L. Fariselli 4 , G. Beltramo 1 

1 

CENTRO DIAGNOSTICO ITALIANO, Cyberknife Radiosurgery Dept., Milan, 

Italy 

2 

CENTRO DIAGNOSTICO ITALIANO, Imaging Dept., Milan, Italy 

3 

H.S.CARLO, Surgical and Oncological Dept, Milan, Italy 

4 

NEUROLOGICAL INSTITUTE C.BESTA FOUNDATION CENTRO DIAGNOSTICO 

ITALIANO, Radiotherapy Dept, Milan, Italy 

Purpose: to assess the feasibility of CK stereotactic radiotherapy in the treatment 

of pancreatic malignant neoplasm. 

Materials: from December 2004 to August 2007, 16 patients with pancreatic 

malignant neoplasm were treated at our Institution. 13 pts presented with 

pancreatic carcinoma, 2 pts with symptomatic metastasis, from lung and renal 

cancer, and 1 patient with a pancreatic recurrence of colic carcinoid. Six 

patients with pancreatic adenocarcinoma relaps after surgical resection followed 

adjuvant radiotherapy with doses ranged from 45 - 60 Gy (4/6), was 

treated with CK stereotactic radiotherapy . In other 3 pts CK Stereotactic radiotherapy 

was administred after surgical bilyar bypass. In six patients with 

inoperable cancer Ck was administered with a pain control intent. All pts with 

metastatic lesions received Ck radiation treatment after surgical excision. In 8 

of 16 pts a Gemcitabine-based chemotherapy scheme was proposed before 

ck radiotherapy treatment. 14 patients received 3 fractions of 8-9 gy /fraction, 

in 2 patients 1 fraction of 10 gy was administered 

Results: With a median follow up of 17 months (2-38.5), we observed a 

median survival time of 6.5 months (range 2 27.8 ) in patients treated after 

pancreatic cancer relapse with a median survival time from diagnosis of 32 

months (17.1 37), 6.8 months (range 2.4 - 26) in inoperable patients and 

3.4 months (range 3 3.8) in patients with metastatic pancreatic desease.No 

patients manifested collateral effects greater than G2. 

Conclusions: dose escalation clinical trials are mandatory to establish the 

best treatment scheme for patients affected with newly diagnosed pancreatic 

carcinoma. Feasibility of palliative stereotactic radiation therapy with CyberKnife 

should be studied for selected patients affected with relapsed pancreatic 

carcinoma or pancreatic metastasis. 

691 poster 

CYBERKNIFE STEREOTACTIC RADIATION THERAPY FOR HEPATIC 

TUMORS : PRELIMINARY RESULTS ON 30 PATIENTS 

X. Mirabel 1 , F. Bonodeau 2 , S. Dharancy 3 , C. Duburque 4 , O. Romano 5 , 

S. Dominguez 6 , T. Lacornerie 1 , A. Adenis 6 , E. Lartigau 1 

1 


2 

CENTRE OSCAR LAMBRET, Radiology, Lille, France 

3 

CHRU, Gastroentérologie, Lille, France 

4 

HÔPITAL SAINT PHILIBERT, Department of Hepato-gastro-enterology, 

Lomme, France 

5 

CHRU, Unité d’oncologie, Lille, France 

6 

CENTRE OSCAR LAMBRET, Cancérologie digestive, Lille, France 

Purpose: CyberKnife allows the delivery of hepatic stereotactic radiotherapy 

(HSRT) synchronized to the respiration.The objective of this work is to assess 

preliminary results on feasibility, toxicity and response on the first 30 patients 

treated in Lille. 

Materials: From June 2007 to January 2008, 30 patients (18 male and 12 

female) with hepatic tumors were irradiated with the CyberKnife : 13 primary 

hepatic tumors (11 hepatocarcinomas and 2 cholangiocarcinomas) and 17 

metastases (13 were from colorectal cancer). 4 patients had 2 lesions and 

1 had 4 metastases. Cirrhotic patients were classified Child A5 to B8, hepatocarcinomas 

Okuda I or II, BCLC A1 to C. All patients with hepatic metastases 

had been previously treated by chemotherapy (17/17), surgery (13/17) 

or radiofrequency ablation (2/17). Treatment indications were discussed at 

the multidisciplinary gastro-intestinal oncology panel in the presence of surgeons 

and radiologists. All patients signed an informed consent. Toxicities 

are recorded in a prospective manner. Response is assessed according to 

RECIST criteria.Doses consisted of 45 Gy delivered in 3 fractions over 10 

days for primary hepatic tumors and 40 Gy in 4 fractions in 2 weeks for secondary 

hepatic tumors. The dose is prescribed to the 80% isodose. CTV 

consisted of 1 cm of healthy liver around the GTV. The PTV is an extension 

of the CTV of 1.5 mm, CyberKnife accuracy for moving targets. 

Results: Fiducials (median 4, 3-7) were implanted under local anesthesia 

and CT guidance in all patients without toxicity. All treatments were delivered 

as planned with tracking of the respiratory movements, a mean number 

of beams of 147, and mean duration per fraction delivery of 106 minutes.28 

patients are evaluable for toxicity during the treatment and at 6 weeks. Nausea 

and vomiting (43%) and hepatic pain (32%) were the most frequently reported 

toxicity. 2 patients experienced grade 3-4 toxicities (hepatic cytolysis 

and vomiting). At 3 and 6 month, the main toxicity is hepatic pain (4 patients 

grade 1-2), gastritis lesions and duodenal ulcer in 3 patients (2 grade 2 and 

1 grade 3.1 patient died from decompensated cirrhosis 2 months after HSRT 

for hepatocarcinoma without any cytolysis following treatment. Her cirrhosis 

was Child B8 before treatment.20 patients are evaluable for response with 

more than 3 month follow-up. 8 partial response (40%) and 12 stable disease 

(60%) are observed. 2 stable patients had a recurrence in the treated zone 

and 4 developed hepatic (2) and pulmonary (2) metastases. 

Conclusions: HSRT is feasible and toxicity is minimal even in patients previously 

operated and treated with chemotherapy or in cirrhotic patients.Taking 

into account duodenal toxicity, it seems legitimate to put strict dose constraints 

on DVH to the stomach and the duodenum.HSRT with CyberKnife 

is a new therapeutic option potentially curative for intrahepatic malignant lesions. 

It adds further to the already available therapeutic methods. 

692 poster 

CYBERKNIFE STEREOTACTIC RADIOTHERAPY/RADIOSURGERY 

IN THE TREATMENT OF PATIENTS AFFECTED WITH LIVER 

MALIGNANT NEOPLASM. 

L. Bianchi 1 , M. Possanzini 1 , L. Brait 2 , A. Bergantin 2 , F. Locatelli 2 , A. 

Brambilla 3 , M. Meregalli 3 , G. Beltramo 1 , L. Fariselli 4 

1 

CENTRO DIAGNOSTICO ITALIANO, Cyberknife Radiosurgery Dept., Milan, 

Italy 

2 

CENTRO DIAGNOSTICO ITALIANO, Department of Imaging, Milan, Italy 

3 

H. S. CARLO, Surgical and Oncological, Milan, Italy 

4 

NEUROLOGICAL INSTITUTE C. BESTA, Radiotherapy, Milan, Italy 

Purpose: to valuate the technical and clinical feasibility and the collateral 

effects of CyberKnife stereotactic radiotherapy/radiosurgery on patients affected 

with liver malignant neoplasm. 

Materials: Eight patients with 10 expansive hepatic lesions (3 cholangiocarcinoma, 

1 hepatocarcinoma, 2 colic, 2 breast, 1 pancreatic and 1 renal 

metastasis) have been treated with CyberKnife stereotactic radiotherapy/radiosurgery. 

All patients, except one, presented with A or B Child Pugh 

stage. In the group of patients affected with metastatic disease, the one with 

two colic metastasis has been treated with 18 Gy in single shoot, other 2 patients 

(2 breast and 1 renal metastasis) received 3 fraction of 8 Gy/fraction 

and the last received 3 fractions of 10 Gy/fraction. In the second group, patients 

affected with cholangiocarcinoma , received 4 fractions of 6.5 to 9 Gy/fr., 

while patient with Hepatocarcinoma has been treated with 5 fractions of 6.5 

Gy. 

Results: With a median follow up of 4.5 months, we achieved complete response 

in 3 patients (37.5 %), partial response in 1 (12.5%), stable desease 

in 2 (25%) and local progression in 2 (25%) after treating Cyberknife. Treatment 

response was assessed by abdominal ct and hepatic angiography. All 

patients manifested mild complications including mild nausea, abdominal discomfort, 

and leukopenia /thrombocytophenia while one patient with cirrhosis 

HCV-related and HIV was been hospitalized for hepatic insufficiency after 10 

days from the end of CyberKnife radiotherapy cycle. 

Conclusions: stereotactic radiotherapy with CyberKnife is a safe and effective 

local treatment in the therapy of malignant masses of the liver. Caution 

is necessary in that patients in which the hepatic function is compromised. 

Studies of dose-escalation are necessary to determine the lower effective 

dose to be prescribed in case of primitive or metastatic hepatic masses.

693 poster 

EVALUATION OF CLINICAL AND HISTOPATHOLOGICAL FACTORS 

AFTER NEOADJUVANT TREATMENT OF ADVANCED RECTAL 

CANCER 

A. Nikolenyi 1 , K. Hideghéty 2 , Z. Nagy 2 , I. Németh 3 , L. Tiszlavicz 3 , A. 

Maráz 2 , A. Cserháti 2 , J. Bontovics 2 , L. Varga 4 

1 UNIVERSITY OF SZEGED, Department of Oncotherapy, Szeged, Hungary 

2 UNIVERSITY OF SZEGED, Clinic of Oncotherapy, Szeged, Hungary 

3 UNIVERSITY OF SZEGED, Department of Pathology, Szeged, Hungary 

4 UNIVERSITY OF SZEGED, Clinic of Surgery, Szeged, Hungary 

Purpose: Investigation of protein expression profile in correlation to clinical 

and morphological features after combined preoperative chemo-radiation for 

advanced rectal cancer. 

Materials: We introduced long course chemoradiation in the treatment of 

advanced rectal cancer in 2005. In this study 54 patients, age:61,1 (42-85) 

years, 38 males and 24 females, with 85% T3-T4 and 39% N+ tumours, were 

treated with 350 mg/m2 5FU- 20 m/m2LV (bolus) iv. on days 1-5 and 21-25 

concomitant with 45 + 5,4 Gy 3D conformal radiotherapy 6-10 weeks before 

surgery. All patients irradiated with thermoplastic mask fixation on belly cushion 

of AIO SolutionTM(ORFIT) had completed the neoadjuvant therapy. Radiation 

was delivered from 4 and 6 fields. Toxicity was graded using CTCAE 

0.3. We evaluated the clinical parameters and treatment outcome in correlation 

to pathological responce (pTNM staging and Mandard score(TRG)). 

Formalin fixed, paraffin embedded surgical specimens (n=23) were studied 

for p53, Bax, β-catenin, APC, EGFr, MDR, Villin, Cox-2, MLH1, MSH-2 expression 

by tissue array automated multiplex immunohisto-chemic method. 

Statistical analysis included χ2 and Kruskal-Wallis tests. 

Results: We introduced long course chemoradiation in the treatment of advanced 

rectal cancer in 2005. In this study 54 patients, age:61,1 (42-85) 

years, 38 males and 24 females, with 85% T3-T4 and 39% N+ tumours, were 

treated with 350 mg/m2 5FU- 20 m/m2LV (bolus) iv. on days 1-5 and 21-25 

concomitant with 45 + 5,4 Gy 3D conformal radiotherapy 6-10 weeks before 

surgery. All patients irradiated with thermoplastic mask fixation on belly cushion 

of AIO SolutionTM(ORFIT) had completed the neoadjuvant therapy. Radiation 

was delivered from 4 and 6 fields. Toxicity was graded using CTCAE 

0.3. We evaluated the clinical parameters and treatment outcome in correlation 

to pathological responce (pTNM staging and Mandard score(TRG)). 

Formalin fixed, paraffin embedded surgical specimens (n=23) were studied 

for p53, Bax, β-catenin, APC, EGFr, MDR, Villin, Cox-2, MLH1, MSH-2 expression 

by tissue array automated multiplex immunohisto-chemic method. 

Statistical analysis included χ2 and Kruskal-Wallis tests. Results Initially 70 

% of the tumours (length of 4,9 (± 3,1)cm) located in the lower third of the 

rectum (distance from anal verge 7,8(± 6,4) cm). Gross tumor volume (GTV), 

contoured on planning CT was 140,7 (± 116,4) cm3. Grade 1-2 diarrhoea 

in 34, cystitis in 8, proctitis in 9, and perianal dermatitis in 15 cases were 

detected. No treatment break was indicated due to toxicity. Sphincter preserving 

surgery was performed in 71%. During 24,6 (12-33) months follow 

up 1 pat. died after 19 month in metastatic disease, 53 are alive. Statistically 

ypN+ status and TRG score, furthermore the close circumferential resection 

margin showed significant correlation to disease progression. Pathological tumour 

responce significantly correlated with p53, COX2 and BAX expression. 

Association between MDR and treatment resistence was obtained. 

Conclusions: : Initially 70% of the patients could not be operated with 

sphincter preservation, from them 46% live with well functioning sphincter 

after 2 years. Therapeutic index could be improved with new combinations 

and dose escalation. However non-responders (lack of downstaging, ypN 

positivity and high TRG score) experience controvers effect from long course 

neoadjuvant treatment. Predictive value of p53, COX2 and BAX expression 

should be further studied. Pathological examination of tumour samples may 

provide further information for proper patient selection. 


694 poster 

S 225 

EVALUATION OF DOCETAXEL AND 5-FLUOROURACIL WITH 

CONCURRENT RADIOTHERAPY IN PATIENTS WITH ESOPHAGEAL 

CANCER 

T. Atsuta 1 , K. Kodani 1 , K. Michimoto 1 , Y. Shimatani 1 , M. Kobayashi 1 , T. 

Ogawa 1 

1 TOTTORI UNIVERSITY FACULTY OF MEDICINE, Radiology, Yonago, Japan 

Purpose: Definitive chemoradiotherapy have become frequently used for 

unresectable esophageal cancer. Although the most common chemotherapeutic 

agents used in conjunction with radiation therapy are cisplatin and 

5-fluorouracil (5-FU), this combination have limited efficacy. More recently, 

taxanes has been found to be an active agent in esophageal cancer with its 

radiosensitizing effect. The aim of this study was to evaluate the clinical outcome 

and the toxicity using the regimen of docetaxel/5-FU and concurrent 

radiation therapy in the management of esophageal cancer. 

Materials: Twenty-four patients with squamous cell carcinoma of the esophagus 

were enrolled. Thirteen patients (54%) had stage III, 2 (8%) had stage 

IVA, and 2 (8%) had stage IVB. Seven patients had operable stage with stage 

I or IIA, but they had medical problem with receiving surgery. Patients received 

protracted infusion of 5-FU 250mg/m2/24 hours on days 1-5, 8-12, 

15-19, 22-26, 29-33 and 36-40, 1-hour infusion of docetaxel 5~10mg/m2 on 

days 1, 8, 22 and 29. Concurrent radiation therapy was performed at a total 

dose of 60Gy in 30 fractions over 6 weeks. No split course was set. Responders 

received chemotherapy for adjuvant treatment. 

Results: Fifteen (48%) patients completed the full course of the protocol, and 

6 patients (25%) received the full dose of radiotherapy but a reduced dose of 

chemotherapy from the initially determined dose. The overall response rate 

was 71% (17/24), and the complete response rate was 38% (9/24). Five 

(50%) of the 10 patients with T4 disease achieved a complete response. 

With a median follow-up duration of 13.8 months, the 2-year survival rate was 

48.5% and the median survival time was 18 months. Major toxicities exceeding 

grade 3 were lymphocytopenia and esophagitis. Four patients developed 

perforation of the esophageal wall. Two treatment-related deaths occurred. 

The incidence of local/regional failure was 17% and the distant failure was 

21%. 

Conclusions: Severe esophagitis was dose-limiting and the dose intensity 

of chemotherapy used in this protocol seemed to be insufficient to control the 

distant metastasis. Based on the overall response rate and survival rate, the 

results obtained from the present protocol did not offer the survival advantage 

compared with the traditional cisplatin/5-FU based regimen. 

695 poster 

EVALUATION OF TOLERANCE AND LOCAL EFFECTIVENESS OF 

EXTRACRANIAL STERATACTIC RADIOSURGERY IN TREATMENT 

PATIENTS WITH LIVER TUMORS . 

B. Jochymek 1 , K. Ficek 1 , H. Urbanczyk 1 , R. Kulik 1 , E. Wolny 1 , L. 

Miszczyk 1 

1 CENTER OF ONCOLOGY, Department of Radiotherapy, Gliwice, Poland 

Purpose: An evaluation of patient‘s tolerance and liver tumors response after 

extracranial stereotactic radiosurgery of patients unproper for the surgical 

resection and chemotherapy . 

Materials: The material comprised 35 patients (16 women and 19 men) aged 

40-81 years (median 62 ) with 56 hepatic tumors which were treated using 

extracranial stereotactic radiosurgery. Total doses varied from 6 Gy to 36 Gy 

and were delivered using 5 to 10 beams. Tumors volumes varied from 0.8 to 

179,5 cc.. In 44 cases tumors were irradiated using single dose varied from 

to 6 Gy to 16 Gy. In 12 cases patents were irradiated three times with fraction 

dose of 12 Gy to the total dose of 36 Gy in overall treatment time of 15 days. 

In 16 cases (22 metastatic lesions) respiratory gating was used, in total irradiating. 

Fractionation method , prescribed dose and gating using depended 

on patients performance status, tumors size and extrahepatic extention .Because 

of relatively short follow up only treatment toxicity and tumor response 

(changes of tumor dimensions) were evaluated. Evaluation was performed 3 

months after the treatment 

Results: 15 patiens were examined after the treatment. Remaning patiens 

were lost from follow up. Changes of 27 tumors diameters was evaluated. In 

the majority of cases the therapy was performed with no significant adverse 

symptoms. Severe symptoms (vomites, end elevation of hepatic enzymes) 

were observed in two case (patients with big tumor volumes 87.0 and 116,1 

cc). In whole evaluated patients gruoup 59% tumors decreased and 41% 

tumors progressed after radiosurgery. In the remaining subgroup (without 

gating) 44% tumors decreased and 56% of tumors progressed after the treatment. 

After gated radiosurgery 88% of tumors decreased and 11% tumors 

progressed . 

Conclusions: Extracranial stereotactic radiosurgery is valuable, non-invasive 

palliative treatment modality giving acceptable acute toxicity and good local 

effectiveness for patient with livertumors, who are not suitable for surgery 

and/or chemotherapy. Effectiveness of radiosurgery with gating could be better 

than radisurgery alone but is more time-consuming. The role of extracranial 

stereotactive radiotherapy should be further investigated.


696 poster 

HEALTH-RELATED QUALITY OF LIFE AFTER ANTERIOR RE- 

SECTION OR ABDOMINOPERINEAL RESECTION FOR RECTAL 

CANCER (ON BEHALF OF THE POLISH COLORECTAL CANCER 

STUDY GROUP) 

D. Tyc-Szczepaniak 1 , L. Pietrzak 1 , K. Bujko 1 

1 MARIA SKLODOWSKA-CURIE MEMORIAL CANCER CENTRE, Department of 

Radiotherapy, Warsaw, Poland 

Purpose: The common belief is that a health-related quality of life (H-RQoL) 

is worse after abdominoperineal resection than after anterior resection. However, 

conflicting results have been described in the literature with majority of 

reports showing similar H-RQoL following those surgical procedures. The aim 

of this report is to explore this issue. 

Materials: The Polish randomized trial compared preoperative short-course 

radiotherapy with preoperative conventionally fractionated chemoradiation in 

312 patients with resectable cT3-T4 rectal cancer. Patients who were without 

disease were asked to answer the EORTC QLQ-C30 (version 2) questionnaire. 

Results: 221 patients (87% response rate) completed the QLQ-C30. There 

were 116 patients with functioning sphincters and 105 patients with stoma. 

The distribution of the main clinical characteristics was well balanced in the 

both groups. The median time from surgery to completion the QLQ-C30 

questionnaire was 12 months, range 3-65 months. There were no significant 

differences in the H-RQoL scores between patients with stoma and without 

stoma. For example, the media of scores for the global QoL status was 50 vs. 

66 points (p=0.87), respectively. A trend (p=0.058) favoring patients without 

stoma was observed in role functioning, i.e. daily activities. 

Conclusions: The H-RQoL scores did not differ in patients with and without 

stoma. 

697 poster 

IDENTIFICATION OF OPTIMAL PET IMAGING CRITERIA FOR 

TREATMENT RESPONSE PREDICTION 

G. Lammering 1 , M. Janssen 1 , M. Oellers 1 , J. Buijsen 1 , P. Lambin 1 , A. 

Dekker 1 

1 DEPARTMENT OF RADIATION ONCOLOGY (MAASTRO), RESEARCH INSTI- 

TUTE GROW, UNIVERSITY, Radiation Oncology, Maastricht, Netherlands 

Purpose: Several criteria are known to influence the SUVs resulting from 

PET imaging. However, these criteria are often not quantified or taken into 

account when using (repeated) PET imaging for the prediction of tumor treatment 

response. Thus, we analyzed in detail the influence of blood glucose 

concentration and the timing of PET acquisition on the SUV determination. 

Materials: Twenty-one patients diagnosed with locally advanced rectal cancer, 

referred for pre-operative radio-chemo-therapy, were included. Repeated 

dynamic PET imaging was performed for each patient, once before starting 

therapy and twice during therapy. All PET-data were corrected for the 

blood glucose concentration (BGC) of the patient and compared to the noncorrected 

PET-data to study the influence of the BGC on FDG uptake. Also, 

the time dependency for SUV determination was calculated from the dynamic 

PET-data. For this, five patients were dynamically scanned during the first 60 

min. after FDG injection and twice statically, at 90 and 120 min. after FDG 

injection to analyze the time span the tumor needs to reach FDG uptake saturation. 

Results: During therapy, intra-patient changes ranged from -20.3 up to 32.8% 

for the BGCs. Comparisons between the SUVs before and after BGC correction 

revealed differences ranging from -23.3 up to 22.9%. None of the investigated 

tumors demonstrated a saturation of FDG uptake within the first 60 

minutes after FDG injection. The time dependencies of the mean and max. 

SUV were calculated as being 0.78±0.41 ∆SUV/10min. (range: 0.15 / 1.59) 

and 1.37±0.70 ∆SUV/10min. (range: 0.37 / 2.76) respectively. Importantly, 

delaying the PET acquisition by 30 min. (90 min. after FDG injection) reduces 

the time dependency of the SUV determination by 6 fold. 

Conclusions: The BGC as well as the time interval between FDG injection 

and the start of PET acquisition strongly influences the SUVs. PET imaging 

starting 90 min. after FDG injection, in stead of the most often used time 

interval of 60 min., reduces the time dependency of SUV determination by 

6 fold. Thus, all criteria influencing the SUVs should be kept constant or a 

correction for the fluctuations should be applied to ensure reliable treatment 

response predictions. 

698 poster 

IMPACT OF REFERRAL TIME AND LIVER FUNCTION ON RADIO- 

THERAPY FOR HEPATOCELLULAR CARCINOMA WITH PORTAL 

VEIN TUMOR THROMBOSIS 

Y. Kim 1 , E. K. Chie 1 , K. Y. Eom 1 , M. Y. Lee 1 , J. H. Yoon 2 , W. Kim 2 , S. 

W. Ha 1 

1 SEOUL NATIONAL UNIVERSITY COLLEGE OF MEDICINE, Radiation 


2 SEOUL NATIONAL UNIVERSITY COLLEGE OF MEDICINE, Department of 

Internal Medicine, Seoul , Korea Republic of 

Purpose: To determine the appropriate timing and impact of liver function on 

the outcome of radiotherapy for the patients with portal vein tumor thrombosis 

(PVTT) caused by hepatocellular carcinoma (HCC) 

Materials: Twenty-one patients underwent radiotherapy for PVTT due to HCC 

between June 2004 and June 2007. Sixteen patients underwent radiotherapy 

only to PVTT and 5 patients to PVT and liver mass. Twenty patients were 

treated by transcatheter arterial chemo-embolization (TACE) 1-10 times (median 

3 times) prior to radiotherapy and one patient was treated by lobectomy 

in addition to TACEs. Radiotherapy was initiated 2 weeks to 22 months (median 

3 months) after the diagnosis. Patients were treated with biologic effective 

dose of 46.8-67.2 Gy10 (median 60 Gy10) with daily fraction size of 2-3 

Gy. Liver function was assessed with Child-Pugh class scoring at the time 

of PVTT diagnosis and at the time of radiotherapy. Child-Pugh class score of 

five was interpreted as intact liver function. Statistical analysis was performed 

using Kaplan-Meier method for survival and log-rank test for univariate analysis. 

Results: Follow-up computed tomography at four months after completion of 

radiotherapy showed a partial response (PR) in 2 patients (10%), stable disease 

(SD) in 13 patients (62%), and progressive disease (PD) in 3 patients 

(14%), respectively. The median survival was not reached at the median 

follow-up period of 15 months. The 1yr survival rate(SR) was 76 %. The patients 

with less tumor burden (tumor volume ≤ 20% of liver volume) showed 

better outcome (p=0.0001). The 1yr SR of patients with impaired liver function 

at the time of radiotherapy was significantly worse compared to that of the 

patients with intact liver function (50 % vs. 100 %, p = 0.003). Worsening of 

the liver function before radiotherapy significantly deteriorated the treatment 

outcome (1yr SR from diagnosis, 56 % vs. 92 %, p=0.02; 1yr SR from radiotherapy 

initiation, 42 % vs. 80 %, p=0.04). However, patients with time 

interval greater than three months from diagnosis of PVTT to radiotherapy 

had improved survival from initiation of radiotherapy (1yr SR, 89 % vs. 38 %, 

p=0.02). 

Conclusions: Results from this study indicate that it is not only the delay in 

initiation of radiotherapy, but also the change in liver function that will have 

significant impact on treatment result for patient undergoing radiotherapy for 

PVTT caused by HCC. Authors suggest that radiotherapy should be offered 

before liver function is declined. 

699 poster 

IMPLEMENTATION OF THE IMRT TECHNIQUE DURING IRRADIA- 

TION OF THE RECTUM AND REGIONAL LYMPH NODES IN THE 

PREOPERATIVE SETTING 

A. Karczewska - Dzionk 1 , T. Piotrowski 2 , E. Wierzchosawska 3 , M. 

Szpakowska 3 , Z. Wareñczak 4 

1 GREATPOLAND CANCER CENTER, I Radiotherapy, Poznan, Poland 


3 GREATPOLAND CANCER CENTER, Radiology, Poznan, Poland 

4 GREATPOLAND CANCER CENTER, Gynecological Oncology, Poznan, 

Poland 

Purpose: Preoperative radiotherapy plays an important role in a therapy of 

patients with rectal cancer. As a result of recent advances in treatment of 

cancer and its detection at an early stage the improvement of survival of 

these patients has been observed.. The risk of developing of a new primary 

cancer stays one of the major of medical concerns for cancer survivors Thus 

the reduction of the dose in the surrounding organs is required. The aim of 

this study was the analysis of the doses in organs at risk and the analysis of 

the accuracy during preoperative irradiation using IMRT technique. 

Materials: Treatment plans of 20 consecutive patients (9 women and 11 men) 

with rectal cancer were analyzed. The disease stage was diagnosed using 

3xT2 MRI technique and was in a range T3N0-N2. Patients were immobilized 

using a standard belly board device. Gross Tumor Volume (GTV) was the tumor 

within the rectum, margin 4 cm proximally and distally, 3 cm laterally. 

Clinical Target Volume (CTV) covered GTV with margin and regional lymph 

nodes (perirectal, presacral and internal iliac), margin 1 cm. For each patient 

2 treatment plans were prepared (Three-field "box technique" and IMRT technique) 

and Dose Volume Histograms (DVH) were obtained. CT slices were 

performed three times during radiotherapy - before planning and on the third 

and fifth day. The Mobility of organs and the accuracy of treatment plan were 

verified. 

Results: Doses were assessed in following organs: bowels, prostate and 

bladder in man, and bowels, vagina, uterus and bladder in woman. Using

IMRT technique median doses in surrounding organs were significantly reduced 

except prostate in men and uterus in woman. Median dose in the 

bladder was reduced in range 70-80% depending on the patient and median 

dose in the bowels was reduced 60-70%. Median dose in the prostate and 

uterus depends on GTV location. Mobility of rectum and blood vessels was 

accordingly 2 and 0.8 cm. The change of IMRT plans concerning GTV, PTV 

or organ at risk motion was not required. 

Conclusions: IMRT seems to be a favorable technique of preoperative radiotherapy 

especially at obese patients. Further clinical trials are required to 

concern the location of possible recurrences. 

700 poster 

INFLUENCE OF THE INTERVAL BETWEEN PREOPERATIVE 

RADIOCHEMOTHERAPY AND SURGERY ON PATHOLOGIC COM- 

PLETE RESPONSE AND DOWNSTAGING FOR RESECTABLE 

RECTAL CANCER 

A. Gomez Caamaño 1 , E. Castro Gomez 1 , U. Anido Herranz 2 , A. Carballo 

Castro 1 , S. Candamio Folgar 2 , A. Varela Pazos 1 , J. Iglesias García 3 , F. 

González Rodríguez 4 , R. López López 2 , C. Porto Vazquez 1 

1 

HOSPITAL CLÍNICO UNIVERSITARIO, Radiation Oncology, Santiago de 

Compostela, Spain 

2 

HOSPITAL CLÍNICO UNIVERSITARIO, Medical Oncology, Santiago de 

Compostela, Spain 

3 

HOSPITAL CLÍNICO UNIVERSITARIO, Department of Gastro-Enterology, 

Santiago de Compostela, Spain 

4 

HOSPITAL CLÍNICO UNIVERSITARIO, Surgery, Santiago de Compostela, 

Spain 

Purpose: The optimal timing of surgery after preoperative radiochemotherapy 

(PRCT) in rectal cancer remains controversial. The aim of this study 

was evaluate the role of interval between PRCT and surgery on pathologic 

complete response (PCR) and downstaging. 

Materials: Between January 1999 and June 2007, 291 consecutive patients 

with resectable cancer of the rectum were treated with PRCT. Median age 

was 68 (range 57-79) years. The preoperative staging before surgery was 

performed with abdominal and pelvic computerized tomography [100%], endorectal 

ultrasound [97.1%] and pelvic magnetic resonance [9.3%]. 66 patients 

had stage II and 225 had stage III. Tumors were located in lower third 

[35%], medium third [44%] and upper third [21%]. Delivered dose of radiotherapy 

was 45-59.4 Gy (1.8 Gy/day). Chemotherapy was 5-fluorouracil (5- 

FU) by continuous i.v. infusion (CI) in 162 patients [55%], 5-FU bolus according 

to Mayo Clinic in 90 patients [31%] and UFT in 39 [14%]. 90 patients were 

treated with Co60, and 201 with LINAC (lineal accelerator). All patients completed 

PRCT. Between radiotherapy and surgery the mean time was 7±2.6 

weeks. Abdominoperineal resection was performed in 108 patients [37%] 

and anterior resection in 183 patients [63%]. The patients were divided into 

four groups based in interval between PRCT and surgery: less than 4-week 

(group A), 4-week to 6-week (group B), 6-week to 8-week (group C) and more 

than 8-week (group D). We have compared time interval with PCR and downstaging, 

using Chi-squared test. 

Results: Group A had 15 patients, group B had 73 patients, group C had 

108 patients and group C had 92 patients. DownT was 60%, 52%, 50% and 

52% on group A, B, C and D, respectively. DownN was 73%, 81%, 72% and 

73% on group A, B, C and D, respectively. Downstaging was 73%, 67%, 

69% and 76% on group A, B, C and D, respectively. No significant difference 

was found in downT, downN or downstaging. PCR was 7%, 11%, 17% and 

24% on group A, B, C and D, respectively; there was significant difference 

(p=0.011). 

Conclusions: A long time interval (more than 6-week) between PRCT and 

surgery provides increased PCR, although larger randomized studies will be 

needed for definitive conclusions. 


701 poster 

S 227 

INTEROBSERVER VARIABILITY IN TARGET VOLUME DELINEATION 

IN POSTOPERATIVE RADIOCHEMOTHERAPY FOR GASTRIC CAN- 

CER 

C. Moretones Agut 1 , D. Leon 1 , A. M. Boladeras 1 , M. Cambray 1 , M. Macia 

1 , V. Navarro 1 , I. Modolell 2 , F. Guedea 1 

1 

INSTITUT CATALÀ D’ONCOLOGIA, Radiation Oncology, L’Hospitalet de 


2 

INSTITUT CATALÀ D’ONCOLOGIA, Medical Physics, L’Hospitalet de 


Purpose: Since the INT0116 trial demonstrated a major survival advantage 

of adding postoperative radiochemotherapy for gastric cancer in 2001, radiation 

oncologists have developed their own methods for delineating volume 

treatments. However, volume delineation is difficult in cases with rich lymphatic 

drainage of the upper abdomen and post-surgical anatomical changes. 

The aim of this study is to determine the interobserver variability between 

radiation oncologists in target volume delineation for adjuvant radiotherapy 

planning in gastric cancer. 

Materials: Four physicians trained in delineating upper abdomen volumes 

were asked to delimitate the planning target volume (PTV) on the same 3D 

CT-images in 9 postoperative radiochemotherapy gastric cancer cases according 

to the MacDonald scheme. Instructions were given to include the 

tumor bed, the remaining stomach if partial surgery was performed, anastomosis, 

the duodenal loop and perigastric, celiac, local paraaortic, splenic, 

hepatoduodenal and pancreaticoduodenal lymph nodes. Enhanced preoperative 

CT images were available. None of the observers (OB) had knowledge 

of the volumes outlined by the others. For each case and physician, 

PTV volume, maximum dimension along 3 axes, and volume discrepancy 

from the main observer (called "A") were calculated. The principal variable 

was volume mismatch between OB A and the other observers (called "B"), 

which were compared using the formula A U B / A intersection B applied to 

the 3D CT-images, which were compared in pairs using boolean operators. 

Analysis of variance with two random effects (researchers and patients) was 

performed. 

Results: Mean volumes were measured as follows: 1410 cm3 for main 

OB and 1231 for OB2, 734.6 for OB3, and 1350 for OB4. The maximum 

dimensions of main observer volume in cm were x:15.76±2.09, 

y:12.8±3.81, and z:16.14±2.70. Discrepancies were 519.9±431.6 cm3 for 

OB2, 652.1±294.36 for OB3 and 225.90±237.07 for OB4. Standard deviation 

ascribed to patients as random effect was 898.6 cm3. Standard deviation 

ascribed to observers was 198.10 cm3 considered as statistically significant 

difference although clinically less evident. 

Conclusions: Despite the difficulties inherent to PTV delineation, the use of 

a structured method minimizes interobserver variability. A preoperative CTscan 

with the patient in radiation position might facilitate PTV delineation.


702 poster 

INTERSTITIAL PDR BRACHYTHERAPY MAY COMPENSATE AN R1 

RESECTION IN ADVANCED RECTO-SIGMOID CANCER 

J. C. Lindegaard 1 , P. C. Rasmussen 2 , K. Tanderup 3 , S. K. Nielsen 3 , T. Tei 

4 , H. Vind Thaysen 2 , S. Laurberg 2 

1 


Denmark 

2 

AARHUS UNIVERSITY HOSPITAL, Department of Abdominal Surgery, 


3 


C, Denmark 

4 

AARHUS UNIVERSITY HOSPITAL, Department of Plastic Surgery, Aarhus C, 

Denmark 

Purpose: To evaluate outcome of extensive abdomino-pelvic surgery combined 

with interstitial pulsed dose rate (PDR) brachytherapy (BT) in locally 

inoperable primary or recurrent recto-sigmoid cancer. 

Materials: 45 patients with rectal (41) and sigmoid cancer (4) referred from 

all parts of Denmark and consecutively operated 2001-2007 were evaluated. 

There were 18 primaries and 27 recurrent cases. Median age was 60 years 

(38-81). Patients were selected for this very extensive treatment when R0 

resection close to muscle and bone in the posterior pelvis was considered 

impossible based on preoperative pelvic MR and palpation in general anaesthesia. 

Patients were screened for disseminated disease by CT and US or 

PET-CT. Thirty-three patients not previously irradiated were given preoperative 

long course chemo-radiotherapy (46-60 Gy/25-30 fx). Following resection 

of tumor and all involved pelvic organs the BT catheters were sutured in parallel 

at a distance of 1-1.5 cm and the tumor bed was marked with silver clips. 

A vertical rectus abdominis myocutaneous (VRAM) flap was used to cover 

the BT catheters and reconstruct the perineal defect. Guided by the preoperative 

MRI and the silver clips the target for PDR BT was contoured at 5 

mm distance from the catheters. The average target volume was 33 cm3. 

Prescribed PDR dose at 0.5 mm from the catheters was 25-30 Gy, 0.5-0.6 

Gy/pulse, 1 pulse/hr. BT was initiated between 1-7 days after the operation. 

Postoperative radiotherapy (25 Gy/15 fx) to the tumor bed only were used in 

patients irradiated for previous disease in the pelvis. 

Results: R0 resection was obtained in 16, R1 in 27 and R2 resection in 2 patients, 

respectively. Bricker bladder was used in 25 and all patients received a 

colostomy. A median of 4.5 (3-8) BT catheters were used to cover the tumor 

bed. The 30 day mortality was 0%. However, one patient did not recover and 

died from septicaemia at day 64. Late toxicity comprised moderate neuropathy 

in 6, fistula in 5, subileus in 3, soft-tissue necrosis in 2, hydronephrosis 

in 2, insufficiency fracture in 1 and ureter leakage in 1 patient. Three year 

overall-survival (OS±SE) was 62%±8, local control (LC±SE) 66%±9 and 

disease free survival (DFS±SE) 38%±8. The number of BT catheters (3-4 

vs. 5-8) significantly (p

Conclusions: In this preliminary investigation, the results indicate that patients 

with unresectable pancreatic cancer are most likely to be benefit from 

125I seed implantation. Excellent palliation of pain was achieved. Intraoperative 

ultrasound-guided 125I seed implantation might be a promising new 

modality to improve the treatment outcome in stage II and III unresectable 

pancreatic cancer, but not in patients with stage IV pancreatic cancer. 

705 poster 

LOCAL RECURRENCE FOLLOWING PRE-OPERATIVE CHEMORA- 

DIOTHERAPY AND TME SURGERY FOR LOCALLY ADVANCED 

RECTAL CANCER TREATED IN THE MOUNT VERNON COLOREC- 

TAL CANCER NETWORK 

A. Nikapota 1 , R. Glynne-Jones 1 , M. Harrison 1 , R. Hughes 1 , S. Mawdsley 

1 , N. Anyamene 1 

1 MOUNT VERNON CANCER CENTRE, Department of Radiotherapy, 

Northwood, United Kingdom 

Purpose: Introduction: Pre-operative chemoradiotherapy (CRT) facilitates 

curative resection and reduces recurrence rates in locally advanced rectal 

cancer (LARC). Incomplete excision with involvement of the circumferential 

resection margin is associated with an increased risk of local recurrence and 

reduced survival. Current radiotherapy field sizes in this setting are controversial, 

partly because the location of locoregional recurrence following CRT 

and TME is poorly documented. Aims: To determine the incidence and the 

sites of loco-regional recurrence after CRT and TME. 

Materials: Between 2000 and 2005 172 patients (pts) have been identified 

from a prospective database as been treated for borderline and unresectable 

LARC. Staging investigations included pelvic magnetic resonance imaging 

and radiotherapy dose was 45Gy in 25 fractions. Chemotherapy agents depended 

on the clinical trials in progress at the time of treatment and included 

fluorouracil, capecitabine, oxaliplatin and irinotecan. Six to 8 weeks following 

chemoradiation pts underwent TME surgery. Follow up data including resection 

margins, sites of recurrence and outcome were obtained 

Results: Of the 172 pts 132 were planned for surgery and 128 proceeded 

with TME surgery following pre-operative CRT. 102 underwent a complete 

resection and 15 had an incomplete resection. Data was not available on 11 

pts. With a median follow up of 60 months local recurrence following complete 

resection was 6.3% and 60% with an incomplete resection. Three of the pts 

with local recurrence have been salvaged with further therapy. Sites of local 

(pelvic) recurrence are 5 pre-sacral space, 1 bilateral ovarian, 2 bladder and 

1 posterior vaginal wall, 2 low pelvis and 1 pelvic brim 

Conclusions: These results show that the overall local recurrence rate in 

our pts is 7.5%, although this rate is much higher in the pts who had an incomplete 

excision. The majority of local recurrences occur in-field close to 

the primary tumour, especially within the pre-sacral space. This information 

is similar to other studies of recurrence after TME and will assist in design of 

future planning algorithms. Further studies need to establish whether combination 

therapy with novel agents and dose intensification to the areas at risk, 

as defined on pre-operative imaging, might reduce local recurrence. The majority 

of pts with local recurrence developed distant metastases suggesting 

altered tumour biology after CRT associated with a worse prognosis. 

706 poster 

LONG TERM ANALYSIS OF PROGNOSTIC FACTORS IN UNRE- 

SECTABLE PANCREATIC CANCER 

G. C. Mattiucci 1 , V. Valentini 1 , A. G. Morganti 2 , E. Ippolito 1 , S. Alfieri 3 , 

A. Antinori 4 , E. Ciurlia 1 , A. Crucitti 4 , G. R. D’Agostino 1 , S. Luzi 1 , D. 

Smaniotto 1 , N. Cellini 1 

1 

CATHOLIC UNIVERSITY OF SACRED HEART, Radiotherapy, Rome, Italy 

2 

CATHOLIC UNIVERSITY OF THE SACRED HEART, Radiotherapy, Campobasso, 

Italy 

3 

CATHOLIC UNIVERSITY OF SACRED HEART, Department of Digestive 

Surgery, Rome, Italy 

4 

CATHOLIC UNIVERSITY OF SACRED HEART, Surgery, Rome, Italy 

Purpose: To analyse factors influencing the outcome in patients (pts) affected 

by locally advanced pancreatic cancers (LAPC) treated with continous 

infusion of Gemcitabine (Gem) associated with external beam radiotherapy. 

Materials: Weekly Gem (100 mg/m2) was given as a 24-hour infusion during 

the course of 3D- radiation therapy (prescribed dose to the nodal drainage 

areas 39.6 Gy and 50.4 Gy to the tumour). After chemoradiation (CT-RT) pts 

with an ECOG PS < 3 received further 5 cycles of sequential chemotherapy 

which consisted of Gem (1000 mg/m2) administered on day 1 and 8 every 21 

days. Response rate was evaluated according to WHO radiological criteria 6 

weeks from the end of CT-RT. 

Results: Forty pts (M/F 22/18; median age 62 yrs, range 36-76) were treated 

from 2000 to 2005. The majority of pts were T4 (n:34; 85%), 6 pts (15%) 

were T3. Sixteen pts (40%) were node positive at diagnosis. Thirty-three 

pts (82.5%) completed the radiation course (RT dose range 27.9-50.4 Gy). 

The median Gem dose administered was 76% (range 32-100%). Thirty pts 

(76.3%) received further Gem-based chemotherapy after CT-RT. A clinical re- 


S 229 

mission either complete (n: 4; 10%) or partial (n:8; 20%) was achieved in 12 

pts (30%). Stable disease was observed in 18 pts (45%). Ten pts (25%) experienced 

disease progression. With a median follow-up of 76 months (range: 

32-98), 3- and 5-year local control (LC) was 38% (median: 11months), 3- and 

5-year time to progression (TTP) was 23% (median: 10 months), 3-and 5-year 

metastases free survival (MFS) was 30% (median: 10 months). Three and 

five year overall survival (OS) was 22.5% (median: 15.5 months). Univariate 

analysis was used to identify factors impacting on LC, TTP, MFS and OS. 

Complete delivery of prescribed RT dose and clinical remission were significantly 

related to all the outcomes analysed (p:


708 poster 

OESOPHAGEAL CANCER SURVIVAL AFTER NEOADJUVANT 

CHEMORADIOTHERAPY FOLLOWED BY SURGERY. 

B. Navalpotro 1 , I. Quispe 2 , E. Puertas 1 , E. Casado 2 , M. Ramos 1 , J. 

Capdevila 2 , J. Ramos 2 , A. Nadal 3 , J. Pradell 3 , J. Tabernero 2 , J. Giralt 1 

1 

VALL DHEBRON UNIVERSITY HOSPITAL, Radiation Oncology, Barcelona, 

Spain 

2 

VALL DHEBRON UNIVERSITY HOSPITAL, Medical Oncology, Barcelona, 

Spain 

3 

VALL DHEBRON UNIVERSITY HOSPITAL, Surgery, Barcelona, Spain 

Purpose: Multimodal therapy comprising neoadjuvant chemoradiotherapy 

(CT-RT) followed by resection has been suggested to improve survival for 

properly selected oesophageal cancer (EC) patients (pts), although the definitive 

role of surgery after CT-RT remains controversial. The achievement of a 

complete pathological response (pCR) or a major response is associated with 

an improved survival. We retrospectively evaluated locally advanced EC patients 

of our institution to determine overall survival (OS) and pCR rate, as 

well as to identify prognostic factors for OS. 

Materials: Single institution retrospective study of EC patients treated with 

CT-RT between 2002 and 2006. Treatment consisted in 3-4 cycles of cisplatin 

(75 mg/m2 day 1) plus 5-fluorouracil (750 mg/m2 continuous infusion days 1- 

5) with concomitant radiotherapy (total dose 50.4 Gy, 1.8 Gy/d), followed by 

surgery 6 weeks after completion of CT-RT. Surgical approach was dictated 

by location of tumour and surgeon preference (The most common was transhiatal 

esophagectomy). OS was calculated using Kaplan-Meier method and 

multivariate analysis was done using Cox model. 

Results: We included 85 pts: median age 56 years; 79 males and 6 females; 

histology: 72% squamous cell carcinoma and 26% adenocarcinoma; upper 

third: 14%, Middle third: 44%; and lower third 42%. Baseline stage IIA 19 

(22%), IIB 5 (6%), III 52 (61%) and IVA 9 (11%). Resection was performed in 

51 (60%) pts after CT-RT, 76% (39 pts) of them showing pathological downstaging 

and 33%(17 pts) pCR. The correlation between clinical baseline and 

pathological staging distribution for 51 resected pts was I= 0/4, IIA= 14/13, 

IIB= 4/8, III= 29/8, IVA= 4/0 and IVB= 0/1, respectively. Median follow-up was 

33.4 months (m). For the whole population median OS was 18.8 m and 5-year 

OS was 30%. Median and 5-year OS were 35.2m/40% for the resected and 

11.6 m/12% for non-resected pts. For the population resected (51 pts), those 

with histopathological tumor regression grade (TRG) 1-2 had an improved 

5-year OS compared with those with TRG 3-5 (82% vs 13%, p

1 , V. Valentini 2 

1 

CATHOLIC UNIVERSITY OF THE SACRED HEART, Radiotherapy Dpt. , 

Campobasso, Italy 

2 

CATHOLIC UNIVERSITY OF SACRED HEART, Radiotherapy Dpt. , Rome, 

Italy 

3 

CAMPUS BIO-MEDICO, Radiotherapy Dpt. , Rome, Italy 

Purpose: In 2002 a USA working group defined the guidelines for 2D fields 

arrangement for post operative radio-chemotherapy approach of gastric cancer. 

The incidence of nodal involvement according to the JGCA location system 

and the availability of 3D conformal techniques, supported the proposal of 

revision of guidelines for CTV and fields arrangement. We investigated if this 

optimization in CTV and in treatment planning, comparing three-dimensional 

conformal approach with the classic anterioposterior-posterioanterior fields, 

determine a better radiation distribution and a better sparing on organ at risk. 

Materials: We selected post-operative gastric cancer patients reported in our 

Institution (Catholic University of Sacred Heart of Rome and Campobasso) 

addressed to dose and timing of RT-CT similar to that used in the trial INT- 

0116. For every patient we performed: a first plan drawed according to 2D 

guidelines radiotherapy; a second plan with 3D conformal techiniques and 

according to the delineation of nodal area at risk for each location. For eight 

patients we additionally performed two plans considering the different location 

of ipothetical tumor. The main endpoint was to evaluate the doses at OAR 

by dose-volume hystograms. The plans were perfomed according to ICRU 

rules. The mean radiation dose were registered and statistical analysis was 

performed using two-tailed t-test. 

Results: We reviewed the data of 24 patients and we consider the dose at 

OAR according to the different location of tumor. For each tumor location 

the t-test about mean dose and 1/3, 2/3 at liver was statistically significant 

for 2D treatment plan. Considering the mean dose and other parameters to 

left kidney, differences were not significant. Mean dose at one third to right 

kidney was 36.8 (3D) and 49.54 (2D) and t-test was statistically significant 

p=0.0003. Also for other location the values were statistically significant. 

Conclusions: A real advantage of 3D conformal treatment plan performed 

according our guidelines appear for right kidney, while not for left kidney. 

About the dose at liver, like as evident by literature, is better in 2D plan compared 

to 3D. On the base of our results we can concludes that this revision 

of CTV and the use of 3D conformal radiotherapy allows to reduce delivery 

dose to kidney. 

713 poster 

PRELIMINARY REPORT FOR COMBINED LOCAL THERAPY WITH 

EXTERNAL BEAM RADIOTHERAPY (ERT) AND PHOTODYNAMIC 

THERAPY (PDT) IN LOCALLY ADVANCED ESOPHAGEAL CANCER 

J. Y. Jang 1 , C. K. Park 2 , Y. K. Oh 1 

1 

CHOSUN UNIVERSITY HOSPITAL, Radiation Oncology, Gwangju, Korea 

Republic of 

2 

CHOSUN UNIVERSITY HOSPITAL, Department of Internal Medicine, 

Gwangju, Korea Republic of 

Purpose: The main treatment in the advanced esophageal cancer is 

chemoradiotherapy or chemoradiotherapy followed by surgery. In spite of the 

advance result of multimodality therapy, a large proportion of the esophageal 

cancer patients were still treated with radiotherapy alone. The survival outcome 

of radiotherapy alone was very poor although radiotherapy has been 

the major treatment modality in advanced esophageal cancer. We report 

the outcome of combined radiotherapy and photodynamic therapy in a local 

therapeutic approach for the treatment of patients with advanced esophageal 

cancer. 

Materials: Six patients with squamous cell carcinoma in esophagus were 

treated curatively with photodynamic therapy (PDT) and external beam radiotherapy 

(ERT). The location of tumor was mid-thoracic portion in 4 patients 

and upper thoracic portion in 2 patients. Tumor length ranged from 2 cm to 

8 cm, with a median of 5 cm. For AJCC Staging, Stage III was found in 5 

patients. ERT was delivered with a total of 50.4~59.4 Gy over 39~59 days 

(median 55.8 Gy per 45 days). All patients were treated with one-time photodynamic 

therapy 7~22 days (median 14 days) before radiotherapy. Four 

patients had past history such as diabetes, hypertension, tuberculosis, cerebral 

infarct. Four patients were chronic alcoholics. Follow-up period was 1~43 

months (median 16 months). 

Results: All patients had improved degree of dysphagia. The complete response 

rate 1~3 months after radiotherapy was 50% (3/6). The median survival 

was 17 month (range 1-43 months). One of 6 patients was dead 1 month 

after radiotherapy due to aspiration pneumonia. The expired patient had had 

a history of tuberculosis managed by thoracotomy. The survival rate in 1 year 

and 2 years were 66.7% (4/6) and 33.3% (2/6), respectively. The significant 

prognostic factor was only the location of tumor (p=0.0177) and others were 

not significant. The median survival was 3 months in upper thoracic portion 

and 19 months in mid-thoracic portion of esophageal cancer. 

Conclusions: PDT is the curative treatment of superficial esophageal cancer 

and palliative treatment of dysphagia or obstruction in advanced esophageal 

cancer. The result of ERT alone in advanced esophageal cancer was poor. 

This paper shows that the combination of ERT and PDT as a local therapy 


S 231 

offers promising results for patients with advanced esophageal cancer. It 

is expected that added systemic modality to combined ERT and PDT will 

improve tumor control and increase survival rate. 

714 poster 

PRELIMINARY RESULT OF SALVAGE REIRRADIATION USING 

HELICAL TOMOTHERAPY FOR LOCALLY RECURRENT RECTAL 

CANCER 

K. C. Keum 1 , Y. B. Kim 1 , S. Y. Kim 1 , J. Kim 1 , D. H. Lee 1 , H. I. Yoon 1 , J. 

H. Cho 1 , J. Seong 1 , C. O. Suh 1 , G. E. Kim 1 

1 YONSEI CANCER CENTER, Radiation Oncology, Seoul, Korea Republic of 

Purpose: Despite adjuvant radio-chemotherapy after total mesorectal excision, 

10~25% of rectal cancer patients still suffer from local recurrence. There 

are few options of treatment for locally recurrent cases. Re-irradiation to 

the pelvis has been avoided for unacceptable risk of normal organ complications. 

The purpose of this study is to evaluate preliminary result of salvage 

re-irradiation using helical Tomotherapy. 

Materials: Between April, 2006 and June, 2007, eight patients after adjuvant 

radio-chemotherapy with locally recurrent rectal cancer were treated with salvage 

re-irradiation using helical Tomotherapy in Yonsei Cancer Center, Seoul, 

Korea. Helical Tomotherapy treatment plans were generated using Tomotherapy 

Hi-Art System, version 2.0. 

Results: Five patients were male, and 3 patients were female. Median age 

was 56 years (range 40-63). Median dose of initial irradiation was 54 Gy. Recurred 

site were 4 presacral areas, 3 pelvic lymph nodes, 1 perineum, and 1 

iliac bone metastasis. Median dose of re-irradiation was 60 Gy over 20 fractions. 

Median interval to salvage re-irradiation was 43 months. There were 

1 complete remission, 5 partial remissions, and 3 stable diseases. During 

median follow-up of 9 months, 2 patients had liver metastasis, 1 patient had 

skin metastasis. Five patients were alive with disease, and 2 patients had 

no evidence of disease at the last follow up visit. There was one death due 

to chemotherapy-related sepsis after tomotherapy. No late gastrointestinal 

toxicity was reported. Genitourinary toxicities were observed in one patient, 

who received suprapubic cystostomy due to ureteral stricture at post-Tomo 7 

months. 

Conclusions: Salvage hypofractionated re-irradiation with Tomotherapy appears 

to be a safe and feasible method with acceptable toxicity, providing 

salvage strategies for locally recurrent rectal cancer despite small number of 

patients and short follow-up periods. 

715 poster 

PREOPERATIVE CHEMORADIATION AND LOCAL EXCISION FOR 

SELECTED T2-T3 RECTAL CANCER PATIENTS: LONG TERM 

RESULTS OF A POOLED ANALYSIS 

A. De Paoli 1 , R. Sigon 2 , S. Pucciarelli 3 , C. Coco 4 , G. Boz 1 , M. L. Friso 

5 6 1 7 3 2 

, A. Gambacorta , R. Innocente , V. Canzonieri , D. Nitti , C. Rossi , 

F. De Marchi 2 , V. Valentini 6 

1 

NATIONAL CANCER INSTITUTE - C.R.O., Radiation Oncology, Aviano, Italy 

2 

NATIONAL CANCER INSTITUTE - C.R.O., Department of Surgical Oncology, 

Aviano, Italy 

3 

UNIVERSITY, Surgery, Padova, Italy 

4 

UCSC, Surgery, Roma , Italy 

5 

UNIVERSITY, Radiation Oncology, Padova, Italy 

6 

UCSC, Radiation Oncology, Roma , Italy 

7 

NATIONAL CANCER INSTITUTE - C.R.O., Pathology, Aviano, Italy 

Purpose: To evaluate long-term results of local excision in selected patients 

with T2-T3 low rectal cancer downstaged by pre-op chemoradiation (CT-RT) 

and treated with local excision 

Materials: Consecutive pts who underwent pre-op CT-RT and surgery with 

curative intent for rectal cancer at three Institutions from December 1993 

to December 2005 were considered for the study. CT-RT consisted of 45- 

50.4 Gy / 25-28 fractions combined with 5FU-based CT. Local excision (LE) 

was performed in selected pts with major clinical response who were unsuitable 

for, or refused, an abdominal-perineal resection. LE was approached 

transanally by removing full-thickness rectal wall. 

Results: Thirty-five pts (M/F: 23/12; median age 69 years, range 46-85 

years) underwent LE following RT-CT at their respective Institutions during 

the considered time interval. Clinical stage of disease, based on transrectal 

ultrasonography and pelvic CT or MRI findings, included 6 T2 N0, 24 T3 N0 

and 5 T3 N1. Median distance from anal verge was 3.4 cm (range 2-5 cm). 

Selection criteria included: APR as expected surgery in 35/35 pts; circumferential 

tumor involvement


native to APR, in a carefully selected subset of rectal cancer pts with stage 

T2-3 N0 disease. This approach is now being prospectively evaluated in selected 

pts with low rectal cancer after major response to pre-op CT-RT in an 

ongoing Italian collaborative study (LEADER Study). 

716 poster 

PREOPERATIVE RADIOCHEMOTHERAPY WITH CETUXIMAB, 

CAPECITABINE AND MITOMYCIN C IN LOCALLY ADVANCED 

RECTAL CANCER 

S. Stojanovic 1 , L. Radosevic-Jelic 1 , I. Popov 2 , N. Borojevic 1 , Z. Krivokapic 

3 , M. Micev 3 , D. Kecmanovic 3 

1 

INSTITUTE FOR ONCOLOGY AND RADIOLOGY OF SERBIA, Radiotherapy, 

Belgrade, Serbia 

2 

INSTITUTE FOR ONCOLOGY AND RADIOLOGY OF SERBIA, Medical 

Oncology, Belgrade, Serbia 

3 

INSTITUTE FOR DIGESTIVE DISEASE, CLINICAL CENTER OF SERBIA, First 

surgical clinic, Belgrade, Serbia 

Purpose: Preoperative radiochemotherapy is accepted as standard treatment 

option in locally advanced rectal cancer treatment. Nowadays, further 

investigations have been conducted in order to find best concomitant 

chemotherapy agents ± targeting therapy with monoclonal antibody. 

Materials: From April to September 2007, at the Institute for Oncology and 

Radiology of Serbia 15 patients with locally advanced rectal cancer were 

treated with concomitant radiochemotherapy. Preoperative radiotherapy was 

conducted on linear accelerators (6, 18 MeV) with tumor dose of 45 Gy in 25 

fractions in isocentric technique, combined with concomitant chemotherapy 

Mitomycin C 7 mg/m 2 at 1, 29 day, Capecitabine 825 mg/m 2 bid continuous 

from 1- 37 day and Cetuximab (400 mg/m 2 , week 1 of cycle 1, initial dose; 

following 250 mg/ m 2 weekly). T3 stage was diagnosed in 10 pts and T4 in 

5 pts. Positive lymph nodes were noted in 11 pts. Four to six weeks after 

radiochemotherapy clinical response rate (cRR) was evaluated by control examinations, 

rectoscopy and abdominal and pelvic CT. Acute toxicity during 

the treatment was scored according to Common Toxicity Criteria version 2.0. 

Results: Acute toxicity was diagnosed in 12 pts (80%). Grades 3-4 toxicity 

was as follows: dermatitis (9/15 pts), diarrhea (2/ 15 pts), leucopenia (2/15 

pts), skin rush (2/15). Out of 15 pts, cRR was achieved in 14 pts (93, 3%) 

(Complete response (CR) in 3 pts and partial response (PR) in 11 pts). After 

evaluation all 15 pts have been radically operated with R0 resection 2 months 

after the end of therapy. Pathohistological down -staging rate was 73, 75%. 

Conclusions: Our study shows promising treatment results on neoadjuvant 

radiochemotherapy with Cetuximab, Capecitabine and Mitomycin C. Further 

investigations and patient’s enrolment are necessary. 

717 poster 

PREOPERATIVE RADIOCHEMOTHERAPY WITH CISPLATIN PLUS 

LV5FU2 IN LOCALLY ADVANCED ESOPHAGEAL CANCER OF UICC 

STAGES II-III, PHASE II STUDY: PRELIMINARY REPORT 

L. Radosevic-Jelic 1 , V. Stankovic 1 , T. Josifovski 1 , P. Pesko 2 , M. Micev 3 , 

I. Popov 4 

1 

INSTITUTE FOR ONCOLOGY AND RADIOLOGY OF SERBIA, Radiotherapy, 

Belgrade, Serbia 

2 

INSTITUTE FOR DIGESTIVE DISEASE, Surgery, Belgrade, Serbia 

3 

INSTITUTE FOR DIGESTIVE DISEASE, Pathology, Belgrade, Serbia 

4 

INSTITUTE FOR ONCOLOGY AND RADIOLOGY OF SERBIA, Medical 

Oncology, Belgrade, Serbia 

Purpose: Prognosis for patients with esophageal cancer is quite poor, specially 

for locally advanced stages. Recent evidence suggests that the adition 

of neoadjuvant radiochemotherapy may improve resectability rate, reduce the 

risk of recurrence and improve survival. We report our preliminary results with 

neoadjuvant radiochemotherapy. 

Materials: 32 patients with locally advanced squamous cell cancer of the 

esophagus have been enrolled since December 2006. in the study which is 

a part of Ministery of Science Project number 145059. According to UICC 

staging system 8 pts have been in clinical stage II and 18 pts in clinical stage 

III. Tumor location was as follows: cervical esophagus 1pt, upper third of thoracic 

esophagus-14 pts, medium-12 pts, lower third-5 pts. Preoperative radiotherapy 

with tumor dose of 50,4 Gy in 28 fractions have been applied with 

concomitant chemotherapy with Cisplatin plus LV5FU2. Four to six weeks after 

radiochemotherapy clinical response rate (cRR) was evaluated by control 

examinations. 

Results: All patients have finished radiotherapy course. All grades toxicity 

was diagnosed in 30 pts (94%). Grade 3-4 toxicity was noted in 14 pts 

(mucositis 10/32 pts, leucopenia 6/32 pts, cardiotoxicity 4/32 pts). In 18 pts 

chemotherapy was not interrupted due to toxicity. Out of 32 pts, clinical RR 

was achieved in 17 pts (53%) (Complete response in 3/32 pts and partial response 

in 14/32 pts). Early progression was detected in 2 pts. 8 pts have 

been radically operated with R0 resection 2 months after the end of therapy 

(resection rate was 25%). According to histopathological assessment, complete 

tumor regression was noted in 3 patients (TRG 1/5), 4 pts had TRG 3/5 

and 1pt had TRG 4/5 

Conclusions: Further enrolment of patients in this study (to reach power 

of more than 80%) with determination of EGFR status and other potential 

predictive factors, are ongoing. 

718 poster 

PREOPERATIVE RADIOTHERAPY AND LOCAL EXCISION FOR 

RADIOSENSITIVE RECTAL CANCER: AN INTERIM ANALYSIS OF 


K. Bujko 1 , P. Richter 2 , M. Kolodziejczyk 1 , M. Nowacki 3 , J. Kulig 2 , T. 

Popiela 2 , T. Gach 2 , J. Oledzki 3 , R. Sopylo 3 , W. Meissner 4 , R. Wierzbicki 

4 , W. Polkowski 4 , T. Kowalska 1 , G. Stryczynska 5 , K. Paprota 1 

1 CENTER OF ONCOLOGY, Radiotherapy, Warsaw, Poland 

2 JAGIELLONIAN UNIVERSITY, Surgery, Krakow, Poland 

3 CENTER OF ONCOLOGY, Surgery, Warsaw, Poland 

4 MEDICAL ACADEMY, Surgery, Lublin, Poland 

5 GREATPOLAND CENTER OF ONCOLOGY, Radiotherapy, Poznan, Poland 

Purpose: The aim is to present preliminary results of preoperative radiotherapy 

and full-thickness local excision for rectal cancer. This treatment is 

attractive due to the organ sparing. 

Materials: Between 2003 and 2007, 47 patients with extraperitoneal tumour 

(≤ 3 cm; G1-2; unfavorable cT1, cT2, borderline T2-3; cN0) were treated 

either with 5 x 5 Gy + 4 Gy boost or with chemoradiation (50,4 Gy + 5.4 Gy 

boost, 1.8 per fraction + 5-fluorouracyl and Leucovorin). Before treatment, the 

mucosa at tumour’s edges was tattooed. Interval between radiation and local 

excision was 6 weeks. Conversion to open surgery was offered to patients 

with poor response (pT2-3, positive margin) due to the high risk of nodal disease 

and expected poor local control. In 22 patients radiotherapy schedule 

was randomly allocated. The remaining 25 patients were treated according to 

the protocol without randomization (phase I-II of the study, refused randomization 

or were unfit for chemotherapy). Short-course radiotherapy received 

33 patients and 14 chemoradiation. 

Results: The acute radiation toxicity I-IIIo was observed in 33% of patients 

in the short-course radiotherapy group and in 71% of the chemoradiation 

group. Resection with the use of retractors was carried out in 53% of patients, 

transrectal endoscope microsurgery in 36%, Kraske procedure in 4% and 

no surgery in 6%. The postoperative complications requiring re-intervention 

were recorded in 11% of patients. The complete pathological response (pCR) 

was 32% in the short-course radiotherapy group and 54% in the chemoradiation 

group. The corresponding values for the rate of patients requiring conversion 

to open surgery were 39% and 23%; 8 patients actually underwent this 

procedure and remaining 7 refused or were unfit. At 14 months of median 

follow-up (range 0-41) local recurrence (including one intramucosal cancer) 

was detected in 7% of patients; all underwent salvage surgery. Late complications 

were observed in 7% of patients. 16% of patients, in whom anterior 

resection was initially deemed possible (n=19), lost their chance for sphincter 

preservation as the abdominoperineal resection had to be performed either 

for conversion or as rescue procedure. 

Conclusions: High rate of organ sparing, acceptable local control, early and 

late toxicity encourage study continuation. Preoperative radiation and local 

excision is controversial for fit patients in whom anterior resection may initially 

be curried out. 

719 poster 

PROGNOSTIC SIGNIFICANCE OF BLOOD TRANSFUSIONS IN 

PATIENTS WITH OESOPHAGEAL CANCER TREATED WITH COM- 

BINED CHEMORADIOTHERAPY. 

J. K. L. Tuan 1 , M. Hawkins 2 , D. Tait 2 

1 

ROYAL MARSDEN HOSPITAL, Unit of Gastrointestinal Radiotherapy , 


2 

ROYAL MARSDEN HOSPITAL, Gastrointestinal Radiotherapy Unit, London, 


Purpose: Anaemia occurs commonly in patients with oesophageal cancer. 

This study evaluates the effect of blood transfusion (BT) on survival outcomes 

in patients with oesophageal cancer treated with combined chemoradiotherapy 

(CRT). 

Materials: From 2000 to 2007, 300 patients with unresectable oesophageal 

cancer were treated with induction chemotherapy followed by CRT. Data on 

haemoglobin (Hb) before and during radiation therapy (RT) and BT requirements 

were abstracted by chart review. Patients had weekly blood counts 

during the CRT treatment. According to the Hb levels measured in the first 

week of RT, patients were stratified to normal Hb group (> or = 12.0 g/dL) 

or anaemic group (< 12.0 g/dL). If Hb decreased to

atio = 20:29. 26 (53.1%) and 22 (44.9%) patients had Squamous Cell Carcinoma 

and Adeno-Carcinoma. 32 (65.3%) and 12 (24.5%) had T3 and T4 

stage disease, respectively. 30 and 19 had N0 and N1 nodal stage, respectively. 

24 (49%) and 22 (44.9%) had AJCC Stage IIA and III, respectively. 

20 (40.8%) relapses and 30 (61.2%) deaths were recorded. The 2-year OS 

and RFS rates were 61.8% and 53.3%, respectively. Median Hb in the first 

week of RT was 11.3 g/dL (range 8.7-15.2). 31 patients had Hb < 12 g/dL, of 

which 21 had BT and 10 did not receive BT as Hb recovered spontaneously. 

15 patients had Hb > 12 g/dL but 4 needed BT during RT. 3 patients did not 

have Hb recorded in the first week, but one received BT. A total of 26 patients 

had BT, and required a median of 2 units (range 2-6). A total of 79 

units were transfused during CRT. The 2-year OS was 58.5% vs 66.7% in 

patients whoreceived BT vs the patients who did not (P=0.72). The 2-year 

locoregional control rate was 56.3% in patients with normal Hb, vs 51.8%, in 

anaemic patients (Hb < 12g/dL) in first week of RT (P = 0.20). 

Conclusions: Anaemia has been used as a surrogate marker for tumor hypoxia. 

In our study, the use of routine BT to correct for anaemia did not result 

in improved patient outcomes. Further research is required to clarify the utility 

of blood transfusion in patients undergoing CRT for oesophageal cancer. 

720 poster 

PROSPECTIVE COMPARISON OF OUTCOME IN PATIENTS WITH 

RESECTABLE THORACIC ESOPHAGEAL CANCER RECEIVING 

CHEMORADIOTHERAPY AND PATIENTS UNDERGOING SURGERY 

H. Ariga 1 , Y. Ogawa 1 , K. Takeda 1 , T. Sakayauchi 1 , K. Fujimoto 1 , K. 

Jingu 1 , K. Nemoto 2 , S. Miyazaki 3 , T. Yoshioka 4 , S. Yamada 1 

1 TOHOKU UNIVERSITY, Radiation Oncology, Sendai, Japan 

2 YAMAGATA UNIVERSITY, Radiation Oncology, Yamagata, Japan 

3 TOHOKU UNIVERSITY, Department of Surgical Oncology, Sendai, Japan 

4 YAMAGATA UNIVERSITY, Medical Oncology, Yamagata, Japan 

Purpose: Esophagectomy remains the mainstay treatment for esophageal 

cancer, though retrospective studies have suggested that the efficacy of 

chemoradiotherapy (CRT) is similar to that of surgery. To determine whether 

CRT can substitute for surgery as the primary treatment modality, a prospective 

comparison of therapeutic outcomes after treatment in patients with resectable 

esophageal cancer who had received CRT and those who had undergone 

surgery was carried out. 

Materials: Eligible patients had resectable T1b-3N0-1M0 thoracic 

esophageal cancer and could tolerate the planned surgical procedure. After 

detailed explanation of each treatment by the surgeon, the patients chose 

either chemoradiotherapy (CRT group) or surgery (OP group). The CRT consisted 

of two cycles of cisplatin of 40 mg/m 2 on days 1 and 8 and fluorouracil 

at 400 mg/m 2 /24 hours on days 1 to 5 and days 8 to 12 repeated every 5 

weeks with split-course concurrent radiotherapy of 60 Gy in 30 fractions. An 

additional two cycles of chemotherapy was performed. Patients with progressive 

disease during CRT and with persistent or recurrent disease after CRT 

underwent salvage resection. All patients were followed up by planned complete 

examination. For assessment of quality of life (QOL) after treatment, 

a cross-sectional QOL survey was performed with the EORTC quality of life 

questionnaire version 3.0. 

Results: Of the 99 eligible patients between January 2001 and December 

2005, 51 patients chose CRT and 48 patients chose surgery. All patients had 

squamous cell carcinoma. There were no significant differences between 

the two treatment groups in age, sex, tumor site and clinical stage. In the 


S 233 

CRT group, 13 patients (25.5%) underwent surgery and 5 patients (9.8%) underwent 

endoscopic mucosal resection as salvage therapy. After a median 

follow-up period of 42.7 months (52.1 months in patients who were alive), 

three- and five-year survival rates were 78.4%, 76.2% in the CRT group versus 

57.0%, 51.6% in the OP group (p = 0.0156), respectively. Multivariate 

analysis showed that earlier clinical stage (p < 0.001) and the CRT group (p = 

0.070) was associated with a reduced mortality rate. In the QOL survey (the 

response rate of 95.4%), the global QOL score was significantly worse in the 

patients undergoing esophagectomy (p = 0.035). 

Conclusions: Among patients with resectable thoracic esophageal squamous 

cell carcinoma, CRT, with salvage therapy if needed, is comparable or 

superior to surgery in the treatment outcome. Preservation of the esophagus 

significantly improves QOL in these patients. 

721 poster 

PROTON BEAM THERAPY FOR HEPATOCELLULAR CARCINOMA 

ASSOCIATED WITH PORTAL VEIN TUMOR THROMBI 

S. Sugahara 1 , H. Nakayama 1 , N. Fukumitsu 1 , K. Fukuda 2 , M. Abei 2 , J. 

Souda 2 , Y. Oshiro 1 , K. Ohara 1 , K. Tsuboi 1 , K. Tokuuye 1 

1 

TSUKUBA UNIVERSITY HOSPITAL, Radiation Oncology, Tsukuba-shi, 

Ibarakiken, Japan 

2 

TSUKUBA UNIVERSITY HOSPITAL, Department of Internal Medicine, 

Tsukuba-shi, Ibarakiken, Japan 

Purpose: To investigate the efficacy of proton beam therapy (PBT) in hepatocellular 

carcinoma (HCC) with portal vein tumor thrombi (PVTT). 

Materials: From February 1991 to September 2005, 452 patients with HCC 

underwent PBT at our institution. Of these patients, 35 presented with tumor 

thrombi in the main trunk (20 patients) or major branches (15patients) of the 

portal vein. Their tumors ranged from 25 mm to 110 mm in size (median, 

55 mm). A median total dose of 72.6 GyE in 22 fractions was given over 31 

days (ranging from 55.0 to 77.0 GyE) was delivered to a target volume that 

encompassed the primary lesion and the PVTT. 

Results: Thirty-two patients were progression-free during a median followup 

period of 20 months (ranging from 2 to 88). Three patients experienced 

progressive disease. Of these patients, one had tumor progression during 

treatment and died 2 months after the beginning of PBT, and two suffered 

marginal recurrences one month after PBT. Of the two patients with marginal 

recurrence, one completed a second course of PBT, successfully, and the 

other died of progressive disease 8 months after initiation of PBT. Of the 

patients who remained progression-free at 20 months, twelve patients were 

alive as of March 2008, 12 had died of multiple tumors in the liver, 4 of distant 

metastases, and 5 of various causes (liver failure, rupture of esophageal 

varices, esophageal cancer, cerebral infarction, and a traffic accident). Local 

progression-free survival rates were 48% at 2 years and 41% at 4 years, 

and the median local progression-free survival was 20 months. Acute toxicity 

of grade 3 or higher was observed in one patient (thrombocytopenia: from 

43000/mm3 to 13000/mm3 during treatment), but no one discontinued treatment 

as a result of toxicity or experienced late toxicity of grade 3 or higher. 

Conclusions: PBT seems effective for patients with HCC and PVTT. Our 

analysis reveals that PBT improves local control and significantly prolongs 

survival in these patients. 

722 poster 

RADICAL DEFINITIVE EXTERNAL BEAM RADIOTHERAPY FOR 

RECTAL CANCER 

A. Sprawka 1 , D. Tyc-Szczepaniak 1 , E. Skrocki 1 , L. Pietrzak 1 , K. Bujko 1 

1 MARIA SKLODOWSKA-CURIE MEMORIAL CANCER CENTRE AND INSTITUTE 

OF ONCOLOGY, Radiotherapy, Warsaw, Poland 

Purpose: Definitive radiotherapy is uncommonly used for rectal cancer. The 

purpose of this retrospective study is to present results of this treatment in 

patients who refused or were unfit for surgery or had unresectable lesions. 

Materials: Between 2000 and 2005, 25 patients (9 with primary tumor and 

16 with pelvic recurrence after surgery) underwent radical external beam radiotherapy 

(22 had 3D treatment planning). The maximal tumor dimension 

ranged from 2 to10 cm, median 5 cm; in 8 patients on digital rectal examination 

the tumor was fixed. The total dose varied from 55 to 68 Gy, median 

64 Gy; 1.8-2.5 Gy per fraction. In 9 patients irradiation was combined with 

bolus 5-fluorouracyl and Leucovorin. The remaining 16 patients were unfit for 

chemotherapy. The follow-up for living patients ranged from 31 to 89 months, 

median 55. One patient was lost to follow-up. 

Results: Local control, defined as lack of tumor progression assessed clinically 

and on pelvic CT, was observed in 44% patients. 24% patients died due 

to the co-morbidity free of cancer. Local recurrences alone were detected 

in 36% of patients; local recurrences concurrent with distant metastases in 

16%; distant metastases alone in 8%. Four patients, 2 with primary tumor 

and 2 with recurrence, were alive and free of cancer from 31 to 66 months 

after treatment. In those 4 patients the maximal tumor dimension ranged from 

6 to10 cm; in 2 of them the tumor was fixed on rectal examination. Five-year 

overall survival, disease-free survival and cumulative incidence of local recur-


rences were 28% (95% CI 6% 50%), 13% (95% CI 0%29%), and 87% (95% 

CI 71% 100%), respectively. Severe late toxicity occurred in 2 patients. 

Conclusions: Our results suggest that radical radiotherapy alone for primary 

or recurrent rectal cancer provides an opportunity for cure. 

723 poster 

RADICAL HYPOFRACTIONATED RADIOTHERAPY FOR EL- 

DERLY/FRAIL PATIENTS WITH OESOPHAGEAL CARCINOMA 

P. Hatfield 1 , D. Sebag-Montefiore 1 , A. Crellin 1 

1 ST. JAMES INSTITUTE OF ONCOLOGY, Clinical Oncology, Leeds, United 

Kingdom 

Purpose: Chemoradiotherapy is well established as the definitive nonsurgical 

treatment for oesophageal cancer. However, not all patients are 

suitable for this, especially those who are elderly, frail, of poor performance 

status or have significant medical co-morbidities. Encouraging results have 

previously been shown with a hypofractionated radiotherapy-alone approach 

for small, localised tumours. We have adopted this regime for elderly/frail patients, 

who nonetheless have localised disease, and present the retrospective 

results of our first 24 patients. 

Materials: Patients considered unfit for either surgery or radical chemoradiotherapy, 

with localised tumours up to 8cm long, were treated with radiotherapy 

(50 Gray in 16 fractions over 22 days). Treatments were CT planned. Medical 

records were analysed retrospectively to assess patient characteristics, 

toxicity and outcome. 

Results: Twenty-four patients were treated in Leeds between Dec 2005 and 

Feb 2008. Median age was 80.6 years (interquartile range 76.7-82.5). There 

were 12 males and 12 females. Only 5 patients (21%) did not have significant 

co-morbidities. Of those that did, 13 (54%) had cardiovascular disease, 

2 (8%) had significant respiratory conditions, 4 (17%) had other cancers 

(myeloma, renal and prostate x2), 2 (8%) gave a history of stroke, 1 (4%) had 

dementia and 2 (8%) had significant renal impairment. Performance status 

varied from 0-2 (0- 12.5%; 1- 50%; 2- 21%; not recorded- 16.5%). Nineteen 

patients (79%) had lower third tumours and five (21%) middle third tumours. 

Mean tumour length was 3.9 cm. Histology demonstrated adenocarcinoma in 

58%, squamous cell carcinoma in 38% and undifferentiated carcinoma in 4%. 

Tumours were staged by CT in all cases and EUS in 46%. T stage (based 

on EUS where available or CT if not) varied from 2-4 (T2- 42%; T3- 54%; 

T4- 4%). Eleven patients (46%) had adjacent N1 nodes considered involved 

(encompassable by treatment volume). All patients successfully completed 

treatment. One patient (4%) developed acute grade 3 dyspnoea following radiotherapy, 

subsequently treated successfully with steroids. No other grade 3 

or above acute or late toxicities were identified. Median overall survival was 

14 months. 

Conclusions: Hypofractionated radical radiotherapy provides a useful treatment 

option for patients that are considered unfit for both surgery and 

chemoradiation on the basis of age, frailty, co-morbidities or performance status. 

724 poster 

RADIOCHEMOTHERAPY OF SQUAMOUS CELL CARCINOMA OF 

ANAL CANAL: AN EXPERIENCE OF 20 YEARS IN 313 PATIENTS AT 

THE TATA MEMORIAL HOSPITAL 

R. Engineer 1 , S. K. Shrivastava 1 , S. Mallick 1 , U. Mahantshetty 1 , R. 

Bhutani 1 , K. Dinshaw 1 


Purpose: Definitive chemoradiation is the standard of care for patients with 

locoregional squamous cell carcinoma of the anal canal. However the optimum 

doses of radiotherapy with and without chemotherapy remains unanswered. 

Therefore, we performed a systematic analysis of clinical data of 

presentation, treatment, outcome, toxicity, survival and other associated prognostic 

factors of the patients of anal canal who received treatment at our Hospital. 

Materials: The medical records of 313 patients treated with radiotherapy from 

the year 1985 to 2005 were studied. The median age of presentation was 

55yrs (22-84) and 75% of patients were males. The T-stages according to 

the 1987 UICC classification were: T1 16 (5.1%), T2 164 (52.4%), T3 109 

(35%) and T4 in 24 (7.7%) patients. There were 93 (30%) patients with nodal 

involvement at presentation. Of the 313 patients, 101 (32.3%) patients received 

radiotherapy (RT) alone, 170 (54.3%) received concomitant chemoradiation 

(CRT) and 41 (13.2%) patients were treated with surgery followed by 

radiation therapy with or without chemotherapy. The radiation dose for the patients 

treated with radical radiotherapy was 45 Gy over 25fractions followed 

by a boost of 20-30Gy with either external beam or brachytherapy (median 

dose 60Gy). One hundred and sixteen patients received brachytherapy as a 

boost after definitive external beam radiotherapy. The chemotherapy regimen 

was fluorouracil (1000 mg/m2) plus mitomycin (1015 mg/m2) if medically fit 

(n=172). Mean follow up was 36 months. 

Results: Complete clinical tumor response rate after radiotherapy was 74.8% 

in the whole group. The rate of local tumor recurrence was 14.3%. Of the 

313 patients, 105 had either locoregional recurrence or persistent disease. 

Of these 63 (60%) could be salvaged by surgery. The 5yr overall (OS) and 

disease free survival (DFS) for the whole group was 70.8% and 58.5% respectively. 

On Univariate analysis, factors affecting DFS and OS were T 

stage, nodal status and dose of RT (> 60 Gy p=0.003) whereas the addition 

of chemotherapy affected OS but not DFS (62.1% vs 44.5% p=0.05). 

There were 60% of patients who were disease free with preserved sphincter. 

On multivariate analysis factors affecting survival were nodal stage (N0 vs N2 

p=0.05, N0 vs N3 p=0.00), addition of chemotherapy (RT vs CRT p=0.04) and 

RT dose (>60Gy vs < 60Gy p=0.00). 

Conclusions: The majority of patients with anal canal carcinoma can be 

treated with curative intent using a sphincter-sparing approach of radiation 

with or without chemotherapy even with advanced disease. There is improvement 

in disease free and overall survival by delivering higher doses of radiation 

and with the addition of chemotherapy. 

725 poster 

RECTAL CANCER: COMPLETE PATHOLOGICAL REMISSION AFTER 

PREOPERATIVE CHEMO-RADIATION. 

E. Nasr 1 , F. Azoury 1 , D. Nehme - Nasr 1 , C. Tohme 2 , M. Ghosn 3 , F. 

Farhat 3 , F. Nasr 3 , R. Sarkis 2 , B. Abboud 2 , J. Kattan 3 , G. Chahine 3 

1 HDF, Radiation Oncology, beirut, Lebanon 

2 HDF, General Surgery, beirut, Lebanon 

3 HDF, Oncology, beirut, Lebanon 

Purpose: To report the patient outcome of preoperative concomitant chemoradiation 

for rectal cancer in our center. 

Materials: We retrospectively reviewed the records of the 24 patients treated 

at our center for rectal cancer between December 2001 and March 2006. 

Median follow up was 23 months (4-70). Median age was 54 years (33-78). 

Gender distribution was 16 men and 8 women. Clinical presentation consisted 

of rectal bleeding in 78% of the cases, constipation in 25%, anal pain 

in 25%, diarrhea in 16.7% and weight loss in 12.5%. The median length of the 

tumors was 62 mm (15-170). The tumor was in the inferior third of the rectum 

in 58.3%, middle third in 37.5% and superior third 4.2%, diagnosed with a 

flexible rectoscope. The most prevalent histological variety was an adenocarcinoma 

in 91.7% of the cases, moderately differentiated in 50%. Initial staging 

was based on the CT scan in 45.8% and endorectal ultrasound in 29.2%. 

Staging was done according to the TNM classification, 4 patients had a stage 

I disease, 5 had a stage II, 12 had a stage III, 2 had stage IV disease and one 

patient could not be staged clinically.Radiotherapy was delivered to the pelvis 

using three fields (two laterals and one posterior) with a linear accelerator, 18 

MV photons for a dose of 45 50.4 Gy in 25 28 fractions. Chemotherapy was 

done concomitantly. Different chemotherapy regimens were used, most were 

5FU based. Continuous infusion of 5FU for 5 days was the most frequently 

used regimen (41.7%). Surgery was done after a median delay of 42 days 

after the initial preoperative treatment. It consisted of a sphincter sparing 

procedure in 15 patients and an abdomino-perineal amputation in 8 patients. 

Results: Three patients had a grade 2 intestinal toxicity (diarrhea), one patient 

had a grade 2 rectal toxicity, febrile neutropenia occurred in one patient. 

Postoperative complications occurred in 3 patients: one anastomosis leak, 

one recto-vaginal fistula and one case of anal incontinence. Complete pathological 

response was observed in six of the twenty four patients (25%). One 

of these patients had however a residual positive lymph node. Down staging 

occurred in six patients. After a median follow up of 20 months local recurrence 

occurred in five patients and metastasis in seven. Local Relapse Free 

Survival at 2 years was 75.2%. Overall Survival was 72.9%. 

Conclusions: Concurrent chemo-radiation for rectal cancer in the preoperative 

setting is feasible and well tolerated. A complete pathological response 

was observed in 25% of the cases. However, the effect on local recurrence 

and overall survival requires a larger number of patients and a longer follow 

up. 

726 poster 

RESULTS OF NOVELTY TECHNIQUE OF 3D IRRADIATION OR 

CHEMOIRRADIATION FOLLOWING RESECTION OF GASTRIC 

ADENOCARCINOMA 

G. Koukourakis 1 , V. Kouloulias 1 , G. Zacharias 2 , K. Kamposioras 3 , D. 

Mauri 3 , G. Maravelis 1 , A. Miliadou 1 , G. Liberopoulou 4 , A. Gouliamos 5 

1 

UNIVERSITY HOSPITAL OF ATHENS ATTIKON, Radiation Oncology, Athens, 

Greece 

2 

PACMER GREECE, Pathology, Athens, Greece 

3 

PACMER GREECE, Department of Medical Oncology, Athens, Greece 

4 

UNIVERSITY HOSPITAL OF ATHENS ATTIKON, Department of Radiation 

Physics, Athens, Greece 

5 

UNIVERSITY HOSPITAL OF ATHENS ATTIKON, Department of Radiology, 


Purpose: Many radiation oncologists are reluctant to use anteroposteriorposteroanterior 

field arrangement when treated gastric carcinoma with adjuvant 

postoperative irradiation due to concers about normal tissue toxicity,

especially in relation to the kidneys and spinal cord. In this report we evaluate 

the results of the novelty technique of 3D postoperative irradiation with or 

without chemotherapy in patients with stomach and gastroesophageal juction 

carcinoma. 

Materials: The records of twenty five patients who underwent resection for 

stomach cancer and received adjuvant radiation or chemo-radiation were retrospectively 

reviewed. The radiation therapy was delivered with a five field 

mono-isocentric 3D conformal arrangement. For each patient, a second radiotherapy 

treatment plan was generated using AP-PA fields. Using dose 

volume histogram analysis (DVH) the two techniques were then compared for 

target volume coverage and dose to normal tissues. 

Results: The conformal technique provides more adequate coverage of the 

target volume with 99% of the planning target volume (PTV) receiving 95% of 

the prescribed dose, compared to 93% using APPA fields. Comparative DVHs 

for the right kidney, left kidney and spinal cord demonstrate lower radiation 

doses using the conformal technique, and although the liver dose is higher, it 

is still well below liver tolerance. 

Conclusions: 3D conformal radiotherapy produces superior dose distributions 

and reduced radiation doses to the kidneys and spinal cord compared 

to APPA techniques, with the potential to reduce treatment toxicity. 

727 poster 

SET-UP VARIABILITY IN RECTAL CANCER PATIENTS AND THEIR 

IMRT PLANS, BASED ON DIFFUSION WEIGHTED MRI (DWMRI). 

S. Van Brussel 1 , F. Deckers 2 , S. Van Laere 3 , A. Sprangers 4 , P. Huget 1 , 

L. Dirix 5 , R. Weytjens 1 

1 

SINT-AUGUSTINUS GZA, Radiotherapy-Oncology, Wilrijk, Belgium 

2 

SINT-AUGUSTINUS GZA, Radiology, Wilrijk, Belgium 

3 

SINT-AUGUSTINUS GZA, Department of Biomedcal Statistics, Wilrijk, 

Belgium 

4 

SINT-AUGUSTINUS GZA, Fysicist, Wilrijk, Belgium 

5 

SINT-AUGUSTINUS GZA, Medical Oncology, Wilrijk, Belgium 

Purpose: As a prerequisite to the implementation of IMRT in the treatment 

of rectal cancer, the systematic and random error, both intrafractionally and 

interfractionally, was quantified. Using these results, we performed an IMRT 

planning study based on DWMRI. The latter evaluates the diffusion capacity 

of water molecules and obtains information about microscopic structures 

such as cell density or necrotic cell clusters and therefore indirectly assesses 

tumour aggressiveness. 

Materials: From September 2007 to January 2008, 19 consecutive patients 

with rectal cancer were treated by conformal 3 or 4 field technique, positioned 

on a belly board. An average of 18 portal images (PI’s) were taken during a 

single fraction. These were obtained during the first three days of the treatment 

and afterwards once a week. For five patients an IMRT planning study 

was performed using 5 to 8 6-MV photon beams. DWMRI was used for dose 

painting. A lesion was defined as being positive for the presence of tumour if 

a focal area of high signal was detected in the rectum in high b-value images 

(b-value 1000 s/mm). 

Results: Regarding the intrafractional PI’s we noted in no direction, a variation 

larger then 2 mm. No further statistics were done because of the limited 

role of such small deviations in clinical practice. Comparing the interfractional 

PI’s, the systematic set-up variation for all patients was 2.20mm in lateral, 

1.85mm in longitudinal and 1.79mm in vertical direction. The random set-up 

deviation was 2.30mm in lateral, 2.20mm in longitudinal and 2.00mm in vertical 

direction. The margin to expand the CTV to a safe planning target volume 

(within an offline correction protocol) should be at least 7.10 mm in lateral 

direction, 6.17 mm in longitudinal direction and 5.87mm in vertical direction. 

Photon IMRT and a simultaneously Integrated Boost ( SIB) were used to treat 

the whole pelvis to 45 Gy and the region with the maximum diffusion restriction 

(on DWMRI with the highest b-value) to 52.5Gy in 25 treatments. Dose 

on small bowel was kept 45 Gy or lower. Dose constraints could be reached 

with 6, 7 as well as with 8 fields. No statistical difference was found between 

the 6 and 8 field plans for PTV, CTV, bladder, femoral heads and dose outside 

PTV. First results of quality control with 2 D array showed a promising gamma 

evaluation. 

Conclusions: In our department no large intrafractional and interfractional 

movements were observed. As patient set-up was shown reliable, we started 

a SIB IMRT planning study, with doses on small bowel as low as possible, but 

with dose painting to 52.5 Gy on regions with highest probability for tumour 

cells, based on DWMRI. Though time consuming, we consider this technique 

as feasible. 

728 poster 

STEREOTACTIC BODY RADIATION THERAPY FOR METASTASES 

TO ABDOMINAL LYMPH NODES 

M. Bignardi 1 , S. Castiglioni 1 , P. Navarria 1 , S. Pentimalli 1 , S. Agostino 

Ninone 1 , P. Lattuada 1 , G. Urso 1 , M. Scorsetti 1 

1 HUMANITAS INSTITUTE, Radiation Oncology, Rozzano (Milan), Italy 

Purpose: To report short-term local control and toxicity in a series of patients 


S 235 

treated with hypofractionated stereotactic body radiation therapy (SBRT) for 

metastases from different tumors to abdominal lymph nodes. 

Materials: Starting in October 2005 we treated 40 patients with SBRT to 

abdominal targets, including 15 nodal metastases from different primary tumors. 

Five metastases were at the hepatic hilus, 10 in other abdominal sites. 

Twelve patients with an isolated nodal metastasis were treated by hypofractionated 

SBRT alone, while 3 patients bearing disease in multiple nodes were 

treated first by extended field 3D-conformal radiotherapy followed by a SBRT 

single dose boost to the largest nodal metastases. Most common primaries 

were colon (3) and gastric cancer (3). Mean patient age was 61 years (range 

38-79). Mean CTV volume was 32 cm3 (range 6.6-87.9). Patient were immobilized 

by means of a vacuum pillow combined with a thermoplastic body 

cast including a styrofoam block for abdominal compression. Planning CT 

was acquired with a stereotactic body frame. Hypofractionated SBRT was 

delivered in 3 to 6 daily fractions, with total doses ranging from 24 Gy to 36 

Gy prescribed at the 80% isodose line encompassing the PTV (30 to 45 Gy 

at the isocenter). Doses were prescribed according to fixed adjustment criteria 

based on normal tissues constraints. When used as a boost, SBRT was 

delivered in a single 8-10 Gy fraction. A kilovoltage on-board imaging system 

was used in order to achieve on-line adjustment of set up inaccuracies 

in each fraction. Up to April 2007 two open-field orthogonal KV images were 

matched to reference DRRs. Later on the same on-board system was used 

to acquire cone-beam CT (CBCT) images at each fraction. CBCT images 

were compared with reference planning CT by means of a manual matching 

followed by automatic refinement. 

Results: Image guidance at each fraction gave us confidence to progressively 

reduce the CTV to PTV margin, from the conventional 5-10 mm margin 

to a residual 3-5 mm margin allowing both for intra-fraction organ motion and 

for inaccuracies in image interpretation. No Common Toxicity Criteria (CTC) 

grade 3-4 acute liver or gastro-intestinal toxicity was observed. Local control 

as well as late toxicity were assessable in 12 patients with adequate follow up. 

Local control at 6 months defined as no radiological evidence of tumor growth 

inside the target lesion at last follow up was achieved in 10/12 cases. No CTC 

grade 2-4 late toxicity was reported at a median follow up of 12 months. 

Conclusions: Although abdominal SBRT has been validated mainly for liver 

tumors, our preliminary results support the hypothesis that high biologically 

effective doses may be given safely by SBRT also in selected patients with 

nodal metastases, provided that doses are carefully tailored according to normal 

tissues constraints. 

729 poster 

STEREOTACTIC RADIATION THERAPY FOR ISOLATED LUNG 

RECURRENCE FROM COLORECTAL CANCER 

C. Choi 1 , M. Kim 1 , S. Yoo 1 , C. Cho 1 , H. Yoo 1 , K. Yang 1 , Y. Seo 1 , J. 

Kang 1 , D. Lee 2 

1 KOREA INSTITUE OF RADIOLOGICAL AND MEDICAL SCIENCES, Radiation 

Oncology, Seoul, Korea Republic of 

2 KOREA INSTITUE OF RADIOLOGICAL AND MEDICAL SCIENCES, CyberKnife 

Center, Seoul, Korea Republic of 

Purpose: The value of surgically resecting metastases to the lung is well 

established. Pulmonary resection can achieve 5-year survival rates of 20% 

to 40%. However, pulmonary resection is only indicated in a relatively small 

percentage of carefully selected patients due to anatomical location of tumor, 

their medical problems, or their refusal to surgery. In these cases, we hypothesized, 

stereotactic radiation therapy (SRT) using the CyberKnife (CK) could 

be used as a alternative local treatment. The efficacy and toxicity of SRS for 

isolated lung recurrence from colorectal cancer(CRC) was evaluated. 

Materials: From June 2003 to December 2006, 13 patients were proven to 

have metachronous isolated pulmonary recurrences from CRC and enrolled 

for this retrospective analysis. Ten patients had single lesion, 2 had double 

lesions and 1 had 3 lesions. Among them, 4 patients received 2nd CK treatment 

due to new single metastatic lesions developed outside the previous 

CK field. So, total lesions treated by the CK were 21. All patients received 

chemotherapy after recurrence and treated with total doses of 39 51 Gy in 

3 fractions The range of planning target volume (PTV) was 0.8 44.8 cc (median 

6.4 cc). Overall survival (OS) rate for 13 patients and local control (LC) 

rate for 21 lesions were calculated as end-points of this study according to 

Kaplan-Meier method. Two groups divided by characteristics of age, sex, status 

of relapse, disease free duration (DFD) from initial operation, number of 

lesions, PTV, and CK doses were compared by log rank analysis in aspect of 

OS and LC. Toxicities related to treatment were evaluated by RTOG toxicity 

score. 

Results: The 3-year OS rate for 13 patients and 3-year LC rate for 21 lesions 

were 61.0% and 56.4%, respectively. The median overall survival time was 

not reached yet. Tumor responses were evaluated at 8 weeks after CK with 

CT and/or PET-CT. Complete response (CR) were shown in 5 lesions, partial 

response (PR) in 6, and stable disease (SD) in 10. There was no progression 

(PD) at that time. The cases with smaller PTV < 6 cc (diameter < 2.3 cm) 

showed better LC rate ( 83.3 % vs 25.3% p = 0.018). There were no any 

other significant prognostic factors for OS and LC. Treatment related severe 

complications, grade 3 or more, was not found during follow-up period. 

Conclusions: Even though the number of cases was limited, the OS and LC 

rate were outstanding and showed similar to the results of cases performed


pulmonary resection. SRS of colorectal pulmonary metastases may have 

a useful role in local control and overall survival for nonsurgical candidates, 

especially in small lesion. 

730 poster 

STEREOTACTIC RADIATION THERAPY IN HEPATOCELLULAR 

CARCINOMA WHO HAD FAILED OTHER TREATMENT MODALITY 

Y. Seo 1 , K. MiSook 1 , S. lYoo 1 , C. Cho 1 , K. Yang 1 , Y. HyungJun 1 , C. 

Choi 1 , J. Kang 1 , D. Lee 2 

1 KOREA INSTITUTE OF RADIOLOGICAL & MEDICAL SCIENCES, Radiation 


2 KOREA INSTITUTE OF RADIOLOGICAL & MEDICAL SCIENCES, CyberKnife 


Purpose: Primary liver cancer is third of cancer incidence in Korea. Although 

a variety of alternative treatment modalities have been attempted, the 5 year 

survival rate of unresectable hepatocellular carcinoma (HCC) is usually less 

than 10%. Stereotactic radiation therapy (SRT) can give higher dose and reduce 

normal liver volume. And it can produce up to three times the biological 

effect produced by fractionated RT. The purpose of this study is to evaluate 

the efficacy of SRT in the localized unresectable HCC which has not available 

treatment modality. 

Materials: Between March 2003 and February 2007, 24 patients were treated 

by SRT (32-51 Gy in 3 or 4 fractions). Four patients had inoperable lesion 

who have rejected other alternative treatment and 20 patients failed previous 

treatment including transcatheter arterial chemoembolization or radiofrequency 

ablation. Sixteen patients had solitary mass and 8 patients had multiple 

masses in the liver. The diameter of treated tumor was 2.6-15.8 cm 

(median 5.2 cm). The follow-up duration from SRT was 4-46 months (median 

15 months). 

Results: The 1-year and 2-year overall survival rate were 54.2% and 35.0%, 

respectively (median 15 months). The 1-year and 2-year local progression 

free survival rate was 62.5% and 46.9%, respectively (median 14 months). 

The group treated by over 70 Gy (NTD2Gy) showed better survival than that 

treated by below 70 Gy (p=0.037). Planning target volume and serum alphafetoprotein 

level before SBRT were also statistically significant prognostic factor 

for survival (p=0.008 and 0.023, respectively). Severe acute radiation toxicity 

was not observed during follow-up period. A patient could receive lobectomy 

after SRT by virtue of decrease of tumor size and expansion of normal 

liver volume and he survives 35 months after SRT. 

Conclusions: Result of SRT is outstanding compared to previous reports in 

localized unresectable liver cancer. Aggressive local modality would improve 

survival in the patient who has unresectable lesion or failed other treatment 

modalities. And through SRT followed by operation, long term survivor can 

be expected. 

731 poster 

THE COMPARISON OF THE CONFORMAL RADIOTHERAPY (CFRT - 

2, 3 AND 4 FIELDS ) AND INTENSITY MODULATED RADIOTHERAPY 

(IMRT) IN NEOADJUVANT RADIOCHEMOTHERAPY FOR PATIENTS 

WITH STOMACH CANCER. 

E. Wolny 1 , J. Wydmanski 2 , A. Tukiendorf 1 , I. Wesolowska 3 , I. Bereza 3 , 

W. Leszczyñski 3 , P. Olejnik 2 , B. Jochymek 1 , R. Suwinski 1 

1 MARIA SKLODOWSKA-CURIE MEMORIAL CENTER OF ONCOLOGY, 

Radiotherapy Department, Gliwice, Poland 


Department of Radiotherapy and Conventional and Intraoperativ Radioth, 



Department of Radiotherapy and Brachytherapy Planning, Gliwice, Poland 

Purpose: To compare CFRT - 2, 3, 4 fields (F) and IMRT in planning of 

neoadjuvant radiochemotherapy in patients with stomach cancer. 

Materials: A treatment planning study was performed to compare 

CFRT(2F,3F,4F) and IMRT for twenty patients with stomach cancer. For each 

patient from this group four treatment plans were performed: 3 for CFRT and 

1 - IMRT. The CFRT plans consisted of two opposite fields (2F), two opposite 

fields and one oblique fields (3F), two lateral and two oblique fields (4F) 

and the IMRT plan. Treatment plans were compared using dose-volume histograms 

and plots of means doses for PTV min, both Kidneys (K) V20, Liver 

(L) V30 and Dmax for Spinal Cord (SC). 

Results: - Minimum dose in PTV (PTVmin) for 2F plan was: 42,7Gy, 3F- 

42,8Gy, 4F 43,18Gy and in IMRT 42,65Gy (p

daily fractions were delivered in a single phase conformal plan. Acute and 

late toxicities were recorded. The primary endpoint was ’in field’ recurrence 

with secondary endpoints: anastomotic recurrence, nodal and distant recurrence. 

Disease free survival (DFS) and OS were measured from time of 

surgery and time of presentation respectively. 

Results: Median age was 58 years (range 39-77). 18 patients (pts) received 

platinum-fluoropyrimidine based pre-operative chemotherapy. 18 had Ivor 

Lewis oesophagogastrectomy, 2 a partial oesophagogastrectomy for Siewerts 

type 1 (13 pts) and type 2 (7 pts) tumours. 9 pts received further 

chemotherapy prior to CRT. 11 received CRT, 9 pts received radiotherapy 

(RT) alone. 1 pt received chemotherapy after RT. CRT was commenced 

within 4.1 months (1- 5.8) after surgery. 2 pts were unable to complete RT: 1 

developed bone metastases and another developed severe respiratory sepsis. 

No G3 or G4 toxicities were reported. 1 pt died within 28 days of completing 

RT with a post mortem confirming death from an unrelated cause. 

"In field’ recurrence was 20% (4 pts), anastomotic recurrence- 10% (2 pts), 

nodal recurrence- 10% (2 pts) and distant recurrence-15% (3 pts). Median 

time to relapse following RT was 2.9 mo (range 1-40.5), median DFS 8.1 mo 

(1.3-33.4) and median OS 14.7 mo (2.8-56.4). 

Conclusions: Localised post operative CRT can be safely delivered to patients 

with involved CRM in adenocarcinoma of the oesophagus. However, 

accurate delineation at radiotherapy planning is essential as most recurrences 

were in field or anastomotic. This suggests a revision of target volume 

definition and radiation dose delivered. Prospective data collection as part of 

a clinical trial would ascertain if there is a therapeutic benefit. 

734 poster 

THE TREATMENT EXPERIENCE OF CYBERKNIFE R○ G4 RADIO- 

SURGERY IN LIVER TUMOR 

S. J. Shim 1 , W. K. Chung 1 , G. Kim 1 , C. K. Min 1 , D. J. Chung 2 , T. H. Lee 

3 

1 

KONYANG UNIVERSITY COLLEGE OF MEDICINE, Radiation Oncology, 

Daejeon, Korea Republic of 

2 

KONYANG UNIVERSITY COLLEGE OF MEDICINE, Radiology, Daejeon, 


3 

KONYANG UNIVERSITY COLLEGE OF MEDICINE, Department of Internal 

Medicine, Daejeon, Korea Republic of 

Purpose: To investigate the feasibility of CyberKnife radiosurgery in liver tumor 

using SynchronyTM respiratory tracking system. 

Materials: From April 2007 to August 2007, a CyberKnife radiosurgery was 

performed on 21 patients with liver tumor. Among them, analysis was performed 

in 13 patients (8 primary tumors, 5 metastases) whose tumor volume 

was less than 300 cm3. Patients were positioned in an individually 

shaped vacuum cusion. All patients underwent ultrasonography-guided percutaneous 

placement of 3-4 fiducials into the liver. The mean tumor volume, 

mean fraction, mean dose, and mean prescribed isodose of patients that we 

treated was 91.4mL, 3, 3900cGy and 74%, respectively. Follow-up CT scanning 

was performed every 2 months. For evaluation of the treatment accuracy, 

we analyzed the correlation error in each patient. 

Results: During the follow-up period of 3-10 months (median 6 months) for 

the above patients, no severe acute toxicity was noticed. For treated area, 

Complete response was observed in 2 of 13, Partial response was observed 

in 10 of 13 and stable disease in 1 of 13. Progression of systemic disease was 

observed in 5. One patient died due to sepsis for liver abscess 3 month after 

treatment. Maximum correlation errors were less than 3mm in all patients 

Conclusions: CyberKnife R○G4 radiosurgery in liver tumor is a feasible treatment 

for most of our patients for local control without acute toxicity. Longer 

follow-up is needed for definitive clinical results. 

735 poster 

TOXICITY DATA FOR CONCURRENT CHEMORADIOTHERAPY WITH 

5-FU AND OXALIPLATIN (FOLFOX) FOR LOCALLY ADVANCED 

ESOPHAGEAL CANCER 

A. Thukral 1 , J. Metz 1 , P. ODwyer 2 , V. Bar Ad 1 

1 

HOSPITAL OF UNIVERSITY OF PENNSYLVANIA, Radiation Oncology, 


2 

HOSPITAL OF UNIVERSITY OF PENNSYLVANIA, Hematology/ Oncology, 


Purpose: The purpose of the current retrospective analysis is to characterize 

the safety and tolerability of oxaliplatin/ 5-fluorouracil given concurrently with 

radiation for patients (pts) with locally advanced esophageal cancer. 

Materials: Between July 2005 and May 2007, eleven pts with clinical T3 

and/or N1 lower esophageal or GEJ adenocarcinoma were treated with preoperative 

(10 pts) or definitive (1 pt) concurrent chemoradiotherapy. The median 

age was 56 yrs. All pts received a pretreatment jejunostomy tube and 

nutritional counseling. A 3D conformal radiotherapy was used encompassing 

the primary tumor and the locoregional lymphatic drainage, to a total dose of 

50.4 Gy preoperatively and 59.4 Gy for definitive treatment. The chemotherapy 

regimen consisted of protracted infusion 5-FU (225 mg/m2/day) through- 


S 237 

out radiotherapy and Oxaliplatin (85 mg/m2) given every 2 weeks. During the 

treatment the chemoradiotherapy-related side effects were assessed at least 

weekly. 

Results: The main toxicities included mucositis, nausea/ vomiting, dysphagia, 

and fatigue. During the first weeks of treatment,

S 238 CLINICAL/DISEASE SITES : GYNAECOLOGICAL TUMOURS 

patients had locally advanced tumors, 1 patient had a tumor arising from a reconstructed 

gastric tube after the resection of esophageal cancer, and 1 had 

early-stage cancer of the gastric remnant (primary gastric cancer was resected 

several years ago). Two of 8 had peritoneal carcinomatosis. The indication 

for radiotherapy included the inoperable state (n=6) or the patients’ refusal 

of operation (n=2). The median prescribed dose was 60Gy/30fr. Seven 

patients underwent various chemotherapy (S-1/CDDP for 2, PAC for 2, S-1 for 

1, 5-FU/LV for 1, FP for 1), and six patients underwent hyperthermia. Median 

follow-up time was 19.5 months (range, 6-39 months). Tumor response was 

evaluated at 2.5-3 months according to the WHO criteria. 

Results: Complete response (CR) was achieved in 4 patients. The treatment 

resulted in partial response (PR) in 3 patients, no change (NC) in 1 patient, 

and there was no progression disease. The response rate was 88%. We experienced 

1 local recurrence among CR cases which was salvaged by EMR. 

Two patients who showed CR are still alive without evidence of the disease 

for more than 2 years, while 2 patients died from other malignancies after 

they kept CR for more than 2 years. Among 4 cases who showed PR or 

NC, one patient is alive with stable disease being treated with chemotherapy 

and hyperthermia, while three patients died from the disease. Grade 3 acute 

gastritis occurred in 2 patients and grade 4 leucopoenia in 1 patient. We 

observed no late toxicities greater than grade 2. 

Conclusions: Although the number of our patients is small, our clinical results 

of semi-radical radiotherapy with chemotherapy and hyperthermia for 

primary gastric cancer seem to be encouraging. The semi-radical radiotherapy 

might be an alternative treatment in the patients with locally advanced, 

inoperable gastric cancer. 

738 poster 

TUMOR DELINEATION BASED ON TIME ACTIVITY CURVE DIF- 

FERENCES ASSESSED WITH DYNAMIC FDG PET-CT IN RECTAL 

CANCER PATIENTS 

M. Janssen 1 , M. Oellers 1 , G. Bosmans 1 , J. Lee 2 , J. Buijsen 1 , D. De 

Ruysscher 1 , P. Lambin 1 , A. Dekker 1 , G. Lammering 1 

1 DEPARTMENT OF RADIATION ONCOLOGY (MAASTRO), RESEARCH INSTI- 

TUTE GROW, UNIVERSITY, Radiation Oncology, Maastricht, Netherlands 

2 DEPARTMENT OF RADIATION ONCOLOGY, CENTER FOR MOLECULAR 

IMAGING AND EXPERIMENTAL, Radiation Oncology, Brussels, Belgium 

Purpose: Accurate tumor delineation is of crucial importance for successful 

treatment in radiotherapy. The main goal of this research was the development 

of an unsupervised tumor delineation method based on time activity 

curve (TAC) shape differences between tumor tissue and healthy tissue. The 

tumor contour resulting from dynamic PET analysis was compared to two 

tumor contours resulting from manual tumor delineation by a radiation oncologist 

and SUV-thresholding of static PET data. 

Materials: Dynamic PET-CT acquisition was performed for 60 minutes starting 

directly after FDG injection. After acquisition and reconstruction, the data 

were filtered to attenuate noise. Correction for tissue motion during acquisition 

was applied. For tumor delineation, the TAC slope-values were k-means 

clustered into 2 clusters. The resulting tumor contour (contour-one) was compared 

to a contour manually drawn by the radiation oncologist (contour-two) 

and one contour generated using a threshold of the maximum SUV (contourthree). 

Results: The tumor volumes of contour-two and -three were significantly 

larger than the tumor volumes of contour-one, with both contour-two and - 

three containing many voxels showing flat TACs at low activities. However, in 

some cases, contour-two did not cover all voxels showing upward TACs. 

Conclusions: Both automated SUV-contouring and manual tumor delineation 

possibly incorrectly assign healthy tissue, showing flat TACs, as being 

malignant. On the other hand, in some cases, the manually drawn tumor 

contours do not cover all voxels showing steep upward TACs, suspected to 

be malignant. These findings suggest a role for tumor contouring based on 

dynamic PET analysis. 

Clinical/Disease sites : Gynaecological 

tumours 

739 poster 

AN INVESTIGATION INTO THE RELATIONSHIP BETWEEN 

MRI-BASED DVH PARAMETERS AND VAGINAL MORBIDITY IN 

CERVICAL CANCER BRACHYTHERAPY 

E. Fidarova 1 , S. Schüssler 2 , J. Dimopoulos 1 , B. Bachtiary 1 , P. Georg 1 , 

D. Berger 1 , C. Kirisits 1 , R. Pötter 1 

1 MEDICAL UNIVERSITY OF VIENNA, Radiotherapy, Vienna, Austria 

2 CHRISTIAN ALBRECHTS UNIVERSITY OF KIEL, Radiotherapy, Kiel, 

Germany 

Purpose: To evaluate vaginal morbidity and investigate whether there is a 

correlation between late vaginal changes and DVH-parameters for vaginal 

mucosa in patients with locally advanced cervical cancer treated by definitive 

radiochemotherapy, including 3D MRI-based brachytherapy. 

Materials: 26 cervical cancer patients (median age 55 yrs, range: 38-80) with 

the FIGO stages IB-IVB (IB=2, IIAB=11, IIB=9, IIIAB=1, IIIB=1, IVA=1, IVB=1) 

were included. The vaginal length, elasticity, macroscopic/microscopic mucosal 

appearance (atrophy, teleangiectasiae (TA), contact bleeding, fibrosis, 

ulceration, and necrosis), the maturation index, and the maturation value 

(MV) were assessed. Vaginal morbidity was recorded using LENT/SOMA 

scale. The vaginal wall was contoured on axial T2-weighted MR images. In 

case of poor visualisation a 4 mm thickness was assumed. Total doses were 

normalised to 2Gy per fraction using LQ equation (EQD2, α/β=3Gy). The 

doses to the most exposed 0.1 (dose), 1, 2, 5 and 10 cm 3 volumes were calculated 

and correlated to an overall LENT/SOMA grade and single adverse 

events. 

Results: Median follow-up was 28 months (range: 4-114). All patients experienced 

late vaginal morbidity. LENT/SOMA grade distribution was as follows: 

G1=9/26 pts (35%), G2=17/26 pts (65%), G3 and G4=0/26 pts. Shortening 

of vagina occurred in 17/26 pts (65%) and decreased vaginal elasticity was 

found in 12/26 pts (46%). TA were detected in the majority of patients: 23/26 

(88%); 11/26 pts (42%) had contact bleeding. TA were mainly located in the 

proximal third of vagina (20/23 pts-87%), but also were present in the middle 

(14/23 pts-61%) and the distal thirds (4/23 pts-17%). Ulceration in the proximal 

third of the vagina was observed only in one patient. In 13 out of 16 

patients with atrophic mucosal changes the MV was below 50. There was no 

significant correlation between either the overall LENT/SOMA score or single 

adverse events and the DVH-parameters. 

Conclusions: The proximal third of vagina was mainly affected by the adverse 

changes. Obtained results demonstrated that vaginal morbidity was 

not significantly correlated to any DVH-parameters which are commonly used 

in 3D MRI-based cervical cancer brachytherapy. New dosimetric concepts 

are required to establish dose volume relationships and dose constraints. In 

addition, the influence of quality of post-treatment care and other co-factors 

have to be assessed in future prospective studies. 

740 poster 

BLOOD PERFUSION IN CERVICAL TUMORS PRIOR TO CHEMO- 

RADIATION IS INDICATIVE FOR TUMOR REGRESSION AFTER 

FOUR WEEKS OF TREATMENT 

U. van der Heide 1 , C. Arteaga de Castro 1 , G. Groenendaal 1 , C. van den 

Berg 1 , J. Roesink 1 , I. Jürgenliemk-Schulz 1 

1 UNIVERSITY MEDICAL CENTER - UTRECHT, Department of Radiation 

Oncology, Utrecht, Netherlands 

Purpose: During external-beam radiotherapy of patients with cervical cancer 

a substantial regression of the tumor volume can be achieved, which benefits 

the effectiveness of intracavitary boosting in the later phase of the treatment. 

The rate of tumor regression varies between patients but can be as large as 

50% of the volume per week. We investigated if the measurement of tumor 

perfusion prior to the treatment can be used to predict this regression. 

Materials: 13 patients with cervical cancer were monitored with MRI scans 

prior to and weekly in the first four weeks of chemo-radiation. T2-weighted 

sagittal and axial scans were made on a 1.5T MRI scanner. Also, a dynamic 

contrast-enhanced series was made in each exam: 15 ml of 0.5M gadolinium- 

DTPA was injected in 10 seconds, followed by a saline flush; Scans were 

repeated 120 times at a 2.4 second interval with a 3D spoiled gradient echo 

sequence (TR/TE 4.9/1.6 ms, flip angle 30, 10 slices, 256x256). The precontrast 

T1 was derived using three pre-scans with different flip angles (4.5, 

8 and 16). Concentration-time curves were analyzed using the Tofts model, 

yielding quantitative 3D maps of the blood flow parameter K trans . 

Results: The average pre-treatment tumor volume was 60 ml [6 154 ml]. 

After 4 weeks of treatment the volume was on average reduced to 35% of the 

pre-treatment volume [9 65%]. However, no correlation was found between 

tumor reduction and pre-treatment tumor volume (p=0.77). The average K trans 

in the tumor showed an increasing trend during the course of the treatment, 

but no significance was reached. However, the 10th percentile of the tumor 

voxels (representing the voxels with poorest perfusion) did show a significant 

increase in K trans after two weeks of treatment, from 0.17 min -1 prior to treatment 

to 0.29 min -1 (p=0.003). A significant correlation was found between 

the 10th percentile K trans prior to treatment and tumor reduction after 4 weeks 

(p=0.04), with a smaller value of the 10th percentile of K trans corresponding to 

a smaller tumor reduction after 4 weeks. 

Conclusions: On average, substantial tumor regression is observed during 

the first 4 weeks of chemoradiation. Also, an increase in blood perfusion is 

found in the poorest perfused part of the tumor. In contrast to initial tumor 

size, the K trans in the poorest perfused part of the tumor prior to treatment is 

indicative of tumor regression during the first 4 weeks of chemoradiation. 

741 poster 

CLINICAL PROFILE OF PATIENTS WITH ENDOMETRIAL CARCI-

NOMA HAVING CO-MORBID ILLNESSES 

M. Kumar 1 , D. Sharma 1 , G. Rath 1 , S. Kumar 1 , A. Bahl 1 , P. Julka 1 

1 AIIMS, Radiation Oncology, New Delhi, India 

Purpose: Association of co-morbid medical conditions with endometrial carcinoma 

is well known. There are few reports regarding the clinical outcome 

of endometrial carcinoma patients having co-morbid conditions. The aim of 

this study was to analyze the clinical profile and outcome of endometrial carcinoma 

patients having co-morbid conditions. 

Materials: A retrospective analysis was carried out of the patients with endometrial 

carcinoma having co-morbid conditions. The clinical case records 

were studied for distribution according to age, co-morbid medical illnesses, 

stage at presentation, pathological characterisitics viz. garde, myometrial invasion 

etc., and treatment. 

Results: Of 133 patients who had endometrial carcinoma, 76 (57%) had associated 

co-morbid conditions. Age of the patients ranged from 39-72 years 

(median age 58 years). Patient population over 60 years was significantly 

higher as compared to patients without any co-morbidity (53% vs 28%). A 

total of 92 medical disorders were found in these 76 patients. Hypertension 

was the commonest disorder followed by diabetes mellitus (DM 28, hypertension 

46, asthma 3, angina/coronary artery disease 5, and hypothyroidism 

10). Seventy two patients underwent surgery (total abdominal hysterectomy 

with bilateral oopherectomy) while remaining 4 could not be operated due to 

medical illnesses. The distribution according to stage, adjuvant therapy, and 

acute treatment related toxicity and disease control was comparable to the 

historical control patients in our institute. 

Conclusions: About 57% patients of endometrial carcinoma at our institute 

present with associated co-morbid conditions. Age at presentation was found 

to be statistically higher in these patients. Rest of the clinical and therapeutic 

factors were comparable. 

742 poster 

COMPARISON AT PLANNING LEVEL BETWEEN VARIAN RAPIDARC 

AND DYNAMIC SLIGING WINDOW IMRT IN CERVIX CANCER. 

L. Cozzi 1 , K. Dinshaw 2 , S. K. Shrivastava 2 , R. Engineer 2 , M. Umesh 2 , 

S. Jamema 2 , A. Fogliata 1 , D. Deshpande 2 


2 TATA MEMORIAL HOSPITAL, Radiotherapy, Mumbai, India 

Purpose: The potential benefits and limitations of the new volumetric aperture 

based intensity modulated arc therapy (RapidArc, RA) from Varian and 

of the "conventional" dynamic sliding window IMRT were investigated on a 

cohort of cervix cancer patients. RapidArc consists of a planning and delivery 

method based on a single arc where multileaf collimator, dose rate and 

gantry speed are optimised simultaneously to achieve the needed degree of 

modulation. RapidArc is based on direct aperture field optimisation. The entire 

process aims to reduce delivery time and to minimise monitor units per 

Gy needed. 

Materials: Plans for 8 patients affected by cervix carcinoma were optimised 

for both IMRT and Rapidarc on the Varian Eclipse system using a non-clinical 

engineering release of the RapidArc optimiser. Plans were computed for 

6 MV beams on a Varian linac equipped with a Millennium multileaf with 

120 leaves. Dose prescription was set to 50 Gy in 2 Gy fractions asking 

for +-5% target homogeneity. Maximum dose to Rectum, bladder and 

small bowel was fixed at 47.5 Gy while additional constraints were asked 

to rectum (mean


treatment. In this ongoing randomized study, completion of accrual, comparison 

of toxicities and outcome is essential to evaluate the exact role of 

concurrent chemoradiation in advance cervical cancers. An interim analysis 

is scheduled in December 2008 to assess the toxicities and early outcome. 

745 poster 

CONSOLIDATIVE WHOLE ABDOMINAL INTENSITY MODULATED 

RADIOTHERAPY (IMRT) FOR HIGH RISK STAGE FIGO III PATIENTS 

WITH OVARIAN CANCER: FIRST RESULTS OF THE OVAR-IMRT-01 

STUDY 

N. Rochet 1 , F. Sterzing 1 , A. Jensen 1 , J. Dinkel 2 , K. Herfarth 1 , K. 

Schubert 1 , M. Eichbaum 3 , A. Schneeweiss 3 , C. Sohn 3 , W. Harms 4 , J. 

Debus 1 

1 

UNIVERSITY OF HEIDELBERG, Department of Radiation Oncology, 


2 

GERMAN CANCER RESEARCH CENTER, Department of Radiology, 


3 

UNIVERSITY OF HEIDELBERG, Department of Gynaecology and Obstetrics, 


4 

ST. CLARASPITAL, Department of Radiation Oncology, Basel, Switzerland 

Purpose: The prognosis for patients with advanced epithelial ovarian cancer 

remains poor despite aggressive surgical resection and platinum-based 

chemotherapy. Despite whole abdominal irradiation’s (WAI) clinically proven 

efficacy the use of radiotherapy in ovarian cancer has profoundly decreased 

mainly due to high toxicity. Modern intensity-modulated radiation therapy 

(IMRT) could allow to spare kidneys, liver and bone marrow while still adequately 

covering the peritoneal cavity with a homogenous dose. The OVAR- 

IMRT-01 study is a single center pilot trial of a phase I/II study to assess the 

feasibility of intensity-modulated WAI. 

Materials: Eight patients with advanced ovarian cancer stage FIGO III, R1 

or R2< 1cm after surgical resection and platinum-based chemotherapy were 

treated with WAI as consolidation therapy using intensity modulated radiation 

therapy (IMRT) to a total dose of 30 Gy in 1.5 Gy fractions. IMRT was applied 

using step-and-shoot-IMRT (n=3) or helical tomotherapy (n=5). Organs 

at risk (OARs) were bone marrow, kidneys, liver, spinal cord, thoracic and 

lumbosacral vertebral bodies and pelvic bones. The planning target volume 

(PTV) included the entire peritoneal cavity plus pelvic and para-aortic node 

regions. 

Results: Intensity-modulated WAI enabled a very homogeneous dose distribution 

with excellent sparing of OARs. Very satisfying target coverage was 

achieved, with a mean V90 of 88%, a mean V95 of 78%, a mean V105 of 14% 

and a mean V110 of 5%. Mean liver dose was 23 Gy and mean kidney doses 

were 10 Gy and 9 Gy respectively. Treatment could be performed without 

interruptions in mean daily time of 25,3 minutes and was well tolerated. Common 

Toxicity Criteria Grade 3 was experienced by 3 patients for neutropenia, 

by 2 patients for gastrointestinal toxicity and by 1 patient for transient liver 

enzyme elevation. Median follow-up is 11 months (1-16), 6 patients are in 

complete remission, 2 are in progress (local progress n=1, hepatic metastasis 

n=1). Small bowel obstruction occurred in 2 patients. 

Conclusions: Intensity-modulated WAI is clinically feasible and can be performed 

on a daily basis. It enabled excellent coverage of the PTV and effective 

sparing of liver, kidneys and bone marrow. Intensity-modulated WAI 

provides a new promising option in the adjuvant treatment of advanced ovarian 

cancer stage FIGO III, toxicity and outcome will be evaluated in a further 

phase II study. 

746 poster 

EVALUATION OF ACUTE NORMAL TISSUE REACTIONS DURING 

RADIOTHERAPY IN WOMAN WITH GYNAECOLOGICAL CANCERS 

DIAGNOSIS. 

Z. Warenczak 1 , A. Roszak 1 , H. Wlodarczyk 1 

1 GREATPOLAND CANCER CENTER, Gynecological Oncology, Poznan, 

Poland 

Purpose: Acute radiotherapy reactions are commonly underestimated and 

underreported in literature. Our aim was to evaluate the incidence and score 

of acute reactions during definitive and adjuvant radiotherapy. 

Materials: Performed was detailed prospective analysis of 263 patients with 

gynaecological malignancies. All patients received both intracavitary (BRT) 

and external beam irradiation (EBRT). We divided all patients in too two 

groups and made analysis between them and in the groups. First group of 

90 patients, with cervical cancer was treated with definitive radiotherapy exclusively 

(RT) or radiochemiotherapy (RCHT). Second group of 173 patients 

with cervical cancer (CC) and endometrial cancer (EC) was treated with adjuvant 

radiotherapy after surgery. Analysis included acute bowel and urinary 

tract reaction. The score of adverse effects was assessed using EORTC and 

CTCAEv3,0 scales. Chi-quadrate, U Manna-Whitneya and Fishera statistical 

models were used for calculations. 

Results: Post radiation reaction during therapy was found in 55,1% of patients. 

Significantly more side effects were observed in definitive than in 

postoperative radiotherapy group (p

Purpose: Examination of acute hematological toxicity and overall survival in 

External Beam Radiation Therapy (EBRT) + cisplatin versus EBRT alone in 

patients with advanced cervical cancer. 

Materials: Between 2003 and 2006, 187 patients with cervical cancer, median 

age 44 years (26-67) have been treated in Dept of Radiotherapy, National 

Hospital of Oncology Sofia and followed for mean period of 24 months 

(3 60). 3 patients were lost of follow up. Clinical stage distribution of all 

patients is the following: IB2- 40%, IIA,B 34%, IIIA,B 23%, IVA 2%. The 

patients from the two groups are comparable in age and clinical stage. Group 

I -102 patients (55 %), treated with EBRT + cisplatin once weekly - 50 mg i.v., 

total dose of 200 mg. Group II - 85 patients (45 %) were treated with EBRlone. 

A post operative radiotherapy for the volume of the pelvis using "Box" 

technique with daily dose of 2 Gy, 5 times per week in total dose of 50 Gy has 

been applied in 148 patients 79%. Definitive radiation therapy using "Box" 

technique with daily dose of 2 Gy, 5 times per week in total dose of 60 Gy 

has been applied in 39 patients 21%. Criteria for inclusion: metastatic pelvic 

lymph nodes N+, positive vaginal, or parametrial margins, lymphovascular 

space involvement, size of lesion > 4cm, advance clinical stage ≥ by FIGO. 

The acute hematological toxicity has been assessed using the Common xicity 

Criteria version 3,0. The values of: HGB, WBC, LY, PLT were checked before 

the start and in the last week of the treatment course. 

Results: Hematological toxicity has been examined in 1-5 grades. tabl.1In 

patients with EBRT + cisplatin (group .), the treatment has been interrupted in 

6 patient (6,2%) for period of 1 week due to hematological toxicity, recovered 

without medication treatment. The overall survival in patients treated with 

EBRT + cisplatin is 81% versus 75% in patients treated with EBRT alone. 

Conclusions: The observed hematological toxicity in patients with advanced 

cervical cancer, treated with EBRT + cisplatin don’t violate the treatment 

course, in comparison with the patients treated with EBRT alone. The unsatisfactory 

overall survival difference - only 6 % observed in group versus 

group II, could be explained with the advanced stage of cervical cancer B-VA 

in 69%, from which - 70% are N+. 

749 poster 

FACTORS INFLUENCING THE TOLERANCE OF PREOPERATIVE 

RADIOCHEMOTHERAPY FOR RECTAL CANCER 

R. Bibik 1 , M. Spych 2 , A. Rychter 1 , J. Fijuth 2 

1 COPERNICUS MEMORIAL HOSPITAL OF LODZ, REGIONAL CANCER 

CENTER, Department of Radiation Oncology, Lodz, Poland 

2 MEDICAL UNIVERSITY OF LODZ, Department of Radiation Oncology, Lodz, 

Poland 

Purpose: Diarrhea is the most common and intense early reaction(ER) during 

preoperative radiochemotherapy of rectal cancer, which may interfere with 

treatment continuation. So the aim of this paper was to identify the clinical 

factors and physical parameters correlating with ER based on treatment 

technique evaluation and patient’s characteristic. 

Materials: 50 consecutive patients with locally advanced rectal cancer 

treated with radiochemotherapy in Copernicus Memorial Hospital were under 

evaluation. Early radiotherapy reactions had being assessed every week during 

radiotherapy treatment according to modified EOTRC/RTOG scale. The 

endpoint for this analysis was the occurrence of radiation enteritis of Grade 3 

or higher. The statistical analyses were performed to determinate risk factors 

of early radiation enteritis. Age, pre-treatment haemoglobin level, bladder 

volume, diet compliance and alcohol use during radiotherapy treatment were 

included to statistical analysis of clinical factors. Following parameters related 

to radiotherapy technique were included to statistical analysis: volumes of intestine 

receiving doses between V5 Gy and V50 Gy, median and maximal 

PTV dose and maximal intestine doses. 

Results: 24 (48%) patients developed Grade 3 enteritis according to modified 

RTOG/EORTC score and 10 (20%) according to standard RTOG/EORTC 

scale. This was the most common and intense side effect during preoperative 

radiochemotherapy of patients with locally advanced rectal cancer. The 

clinical factors influencing development of early gastrointestinal radiotherapy 

complication were: age, haemoglobin level and bladder volume (respectively: 

p=0, 0003, p=0.001, 0,008). Statistical analysis of dose volume histograms 

revealed that there were significant differences between groups with clinical 

manifestation of early radiation enteritis and without this manifestation in volumes 

of bowel included in isodoses 20 Gy(V20) to 45 Gy (V50) (p values 

were between 0,02 and 0,00009). Multivariate analysis of clinical and dosimetric 

parameters showed that the only factors influencing occurrences of 

gastrointestinal complication were volumes of bowel included within the 40 

Gy and 45 Gy isodoses. This indicates that volume of irradiated bowel within 

CLINICAL/DISEASE SITES : GYNAECOLOGICAL TUMOURS 

S 241 

the clinically significant dose is the most important factor for development of 

radiation enteritis. 

Conclusions: Early intestinal, postradiological reaction which is the most 

common and intensive complication during radiochemotherapy of patients 

with locally advanced rectal cancer, influencing the treatment tolerance and 

compliance to protocol. The most important clinical factors influencing development 

of ER were patients younger age and low pre-treatment haemoglobin 

concentration. The factors connected with irradiation technique having impact 

on complications presence were the V 20 Gy to V 45Gy of bowel. 

750 poster 

IMAGE-GUIDED RADIATION DOSIMETRY FOR CERVICAL CANCER 

VERSUS CLASSICAL POINT A DOSIMETRY 

K. Hatano 1 , M. Sakai 1 , H. Araki 1 , T. Imagunbai 1 , N. Tohyama 1 , T. 

Kodama 1 

1 CHIBA CANCER CENTER, Radiation Oncology, Chiba, Japan 

Purpose: Current clinical practice when using intracavitary brachytherapy for 

cervical cancer is to prescribe the dose to Point A. However, this is an empirical 

method using a virtual point unrelated to actual anatomy and does 

not reflect the dose to the tumour. The tumour volume irradiated by the first 

brachytherapy fraction can be very variable when using only Point A for dose 

specification. For different patients, Point A may be situated within the tumour 

volume, or alternatively, outside the volume. Therefore if treatment is 

prescribed on the basis of Point A dose, even when using an optimisation 

procedure, the results can be underdosage or overdosage to the tumour and 

overdosage to organs at risk (OARs). However, when the tumour volume can 

be measured using MR imaging the dose distrribution to the gross tumour 

volume (GTV) can be optimised. Improved conformality of the 3D dose distribution 

for cervical cancer with a reduction in late morbidity. The objective 

of this study is to compare the relationship of toxicity and maximum dose 

of OAR when using classical Manchester Point A dosimetry with the use of 

image-guilded radiation therapy (IGRT) using MR/CT to obtain beter 3D conformality. 

Materials: 1995-2003. The study population consisted of 82 patients treated 

between January 1995 and December 2003, with FIGO stage distribution 

as follows: Ib: 12, IIa:2, IIb:32, IIIa: 2, IIIb: 21, IVa:1, IVb:12.. All cases 

had histologically confirmed squamous cell carcinoma of the uterine cervix. 

All patrients were treated with external beam radiotherapy and MR imageguided 

intracavitary HDR brachytherapy. The mean age of the patients was 

61.3 years (range 33-85 years). The median follow-up period was 60 months 

(range 5-135 months). All patients were treated with 30 Gy whole pelvic irradiation 

followed by a 20 Gy boost to the parametrium. Both CT and MR 

imaging were performed at the times of the first and third brachytherapy fractions. 

CT/MR compatible applicators were used. The GTV was defined by a 

high signal intensity region obtained using MR imaging. The planning target 

volume (PTV) included a 1cm margin cranio-caudally. We delivered 6 Gy per 

fraction to the PTV: one fraction per week, to a total dose of 24 Gy. Before 

1995 a total of 248 patients were treated with the same external irradiation 

technique followed by intracavitary brachytherapy using a Manchester system 

optimisation technique of 6 Gy per fraction to a total dose of 24 Gy to 

Point A). For the two time periods 1995-2003 for IGRTand Before 1995 for 

non-IGRT, the five-year survival rates were compared according to stage, in 

terms of Point A mean dose. We also evaluated the minimum tumor control 

dose. Toxicity was assessed using maximum rectal dose, bladder dose and 

late genitourinary morbidity rates. 

Results: The benefit of OS & RFS at 5 years for stage IIb (92.4% vs. 64.2% 

& 96.7% vs. 83.7%)) & III(68.7% vs. 52.8% & 85.2% vs. 62.5%) patients 

in IGRT group. Total mean Point A dose by HDR-brachytherapy of 

IGRT group was 19.84 Gy(range:4.08-28.40Gy). The total maximum rectal 

dose by HDR-brachytherapy for each group was 21.96Gy (mean: 8.56Gy) 

and 40Gy (mean:25.6Gy), respectively. The maximun bladder dose by 

HDR-brachytherapy for each group was 23.76Gy(mean: 7.2Gy) and 48.2Gy 

(mean: 12.1Gy), respectively. Minimum tumor dose for local control was 4- 

5Gy/fraction to a total dose of 16-20Gy by brachytherapy. From an analysis 

of late rectal complication rate & maximum rectal dose in Non-IGRT 

group, about 44% of the treated patients experienced Grade 1&2 rectal 

bleeding. The maximum rectal dose of these patients was higher than or 

equal to 8Gy/frac. On the other hand, patients whose maximum rectal 

dose/fraction was less than 8Gy experienced no rectal bleeding. From the 

data of Non-IGRT group, we should reduce the maximum rectal dose to less 

than 8Gy/fraction. In IGRT group, maximum rectal dose has been reduced 

to less than 8Gy/frac. IGRT enabled us to reduce the rate of grade 1-2 rectal 

bleeding from 44% to 14% (one third ). IGRT Non-IGRT Morbidity at 

5 years Grade 1 bladder 2/82 18.5% (46/248) Grade 1 rectal 10/82 30.2% 

(75/248) Grade 2 rectal 2/82 13.3% (33/248) Grade 1 bladder/rectal 20.1% 

(50/248) Grade 2 bladder/rectal 13.3% (33/248) Grade 3 bladder/rectal None 

5.6% (14/248) 

Conclusions: Although the patient numbers are small in the IGRT group, 

the results indicate that with IGRT using MR/CT imaging has less morbidity 

than that of the non-IGRT dosimetry. Minimum tumor dose of brachytherapy 

should be 16-20 Gy /4fraction. We have to reduce the miximum rectal dose 

to less than 8Gy/farc. to a total dose of 32Gy by HDR brachytherapy.


751 poster 

IMAGE-GUIDED STEREOTACTIC RADIATION THERAPY IN PA- 

TIENTS WITH ISOLATED PARAAORTIC LYMPH NODE METASTASIS 

FROM CARCINOMA OF UTERUS 

C. Choi 1 , C. Cho 1 , S. Yoo 1 , M. Kim 1 , H. Yoo 1 , K. Yang 1 , Y. Seo 1 , J. 






Purpose: Isolated paraaortic lymph node (PALN) metastasis is defined to be 

a disease confined to PALN only as metastatic site. The survival outcome 

of patients with isolated PALN metastasis is dismal. This result is due to 

the limited effectiveness of salvage therapies. Salvage surgery or radiation 

therapy has a limited role in patients with isolated PALN recurrence because 

of their potential morbidity and mortality are excessive. We hypothesized that 

stereotactic radiation therapy (SRT) using the CyberKnife (CK) system would 

lead to better local control via delivery of higher dose to tumor and this result 

would be translated to survival gain, ultimately. The aims of this study are to 

evaluate the role of SRT as local treatment for isolated PALN metastasis from 

carcinoma of uterus. 

Materials: From September 2002 to October 2007, 30 patients with isolated 

PALN metastasis from carcinoma of uterus, who had received SRT using CK 

at Korea Institute of Radiological and Medical Sciences (KIRAMS), were enrolled 

for this retrospective analysis. All patients were proven to have isolated 

PALN metastasis by computed tomography (CT) and/or positron emission tomography 

(PET)-CT. Twenty-eight patients were uterine cervix cancers and 

remaining 2 were endometrial cancers. Age ranged from 31 to 68 years old 

(median 52 years). The latent time between initial treatment and first relapse 

ranged from 3 to 81 months (median 14 months). After detection of isolated 

PALN metastasis, 25 of 30 patients received chemotherapy with concomitant 

SRT as salvage treatment. Tumor volume ranged from 13.2 cc to 57.3 cc (median 

16.3 cc). The follow-up duration ranged from 3 to 67 months (median 21 

months). Twenty-six patients were treated with SRT, while the remaining 4 

patients with external beam radiation therapy (27 Gy to 45 Gy) followed by 

SRT boost (13 to 33 Gy). Doses of SRT ranged from 33 Gy to 45 Gy (median 

39 Gy) in 3 fractions. Overall survival (OS), local control (LC) rate and disease 

progression-free survival (DPFS) rate were calculated according to Kaplan- 

Meier method. Comparison between prognosis groups was performed by 

log-rank analysis. Toxicities were evaluated using the Radiation Therapy Oncology 

Group/European Organization for Research and Treatment of Cancer 

(RTOG/EORTC) radiation morbidity criteria. 

Results: The 4-year overall survival rate was 50.1 % and median survival 

time was not reached yet. Overall survival rate of symptomatic patients was 

significantly lower than asymptomatic patients (p = 0.002). The 4-year actuarial 

local control rate was 67.4%. Patients with 17 cc or less planning target 

volume (PTV) had significantly higher local control rate (p = 0.09). The 4-year 

disease progression-free survival rate and median time to disease progression 

was 45.0% and 32 months, respectively. Small PTV was a favorable 

prognostic factor (p = 0.043). Grade 3 or more complication requiring hospitalization 

was reported in 1 patient at 18 months after SRT. The patient was 

suffered from ureter stricture and underwent procedure to insert catheter. 

Conclusions: The overall survival rate and local control rate were promising 

with low toxicities. SRT using CK could be regarded as an effective treatment 

modality to treat isolated PALN metastasis from carcinoma of uterus. 

752 poster 

IMRT AS A SINGLE MODALITY IN THE TREATMENT OF LOCALLY 

ADVANCED CARCINOMA OF THE CERVIX 

H. Coomber 1 , H. Al-Booz 2 

1 

BRISTOL HAEMATOLOGY AND ONCOLOGY CENTER, Medical Physics, 


2 

BRISTOL HAEMATOLOGY AND ONCOLOGY CENTER, Clinical Oncology, 


Purpose: Currently, patients with locally advanced carcinoma of the cervix 

who have an anaesthetic/ operative risk or other contraindication to proceed 

with brachytherapy are having lower doses of radiotherapy than planned. We 

are aiming to study the possibility of using IMRT as the sole modality of treatment 

to be able to deliver a radical dose to the PTV and minimal dose to the 

organs at risk, to avoid under-treating this group of patients. 

Materials: The study included ten patients with locally advanced cervical cancer, 

and a performance status of 0/1, who were successful in completing their 

radical dose of External beam radiotherapy (50.4 Gy/ 25 fractions/ 5 weeks) 

with weekly Cisplatin chemotherapy (40mg/m2 IV infusion) between October 

2007 and February 2008. This was followed by three fractions of intra uterine 

brachytherapy and parametrial boost as indicated. The same planning 

CT scans were re-outlined as per IMRT protocol, which is not currently the 

standard modality of treatment in our centre. The GTV, CTV and surrounding 

organs were delineated. Isodoses were checked with the new plan, and 

calculation of the doses achieved to the PTV and the doses received to the 

organs at risk are documented. 

Results: Provisional check to the IMRT DVH’s reveal nearly 90% of the plans 

examined receive the intended dose to the PTV, and only 2% of the plans 

have a rectal dose in excess of 63Gy. More detailed data will be presented at 

the meeting. 

Conclusions: Omitting intrauterine brachytherapy for patients with locally advanced 

cervical carcinoma is possible by delivering the intended radical dose 

by IMRT. We are suggesting that this modality of treatment can be used for 

those who are not fit for brachytherapy, however, this cannot be replacing the 

standard radiotherapy currently used with both external and internal treatment 

until a multi-centre randomised trial takes place and confirm the above. 

753 poster 

INTRAPERITONEAL ALPHA-RADIOIMMUNOTHERAPY OF OVARIAN 

CANCER - PHARMACOKINETICS AND DOSIMETRY OF 211-AT- 

MX35 F(AB’)2 IN A PHASE I STUDY 

E. Haglund 1 , H. Andersson 2 , T. Bäck 1 , C. Divgi 3 , J. Elgqvist 4 , S. Frost 1 , 

J. Himmelman 5 , G. Horvath 4 , R. Hultborn 4 , H. Jensen 6 , S. Lindegren 1 , 

S. Palm 1 , L. Jacobsson 1 

1 

INSTITUTE OF CLINICAL SCIENCES, THE SAHLGRENSKA ACADEMY, 

Radiophysics, Gothenburg, Sweden 

2 


3 

UNIVERSITY HOSPITAL OF PENNSYLVANIA, Nuclear Medicine and Clinicak 

Molecular Imaging Section, New York, USA 

4 

INSTITUTE OF CLINICAL SCIENCES, THE SAHLGRENSKA ACADEMY, 

Oncology, Gothenburg, Sweden 

5 

SAHLGRENSKA UNIVERSITY HOSPITAL, Nuclear Medicine, Göteborg, 

Sweden 

6 

COPENHAGEN UNIVERSITY HOSPITAL, PET and Cyclotron Unit, Copen- 


Purpose: The alpha particle-emitter 211 At labeled to a monoclonal antibody 

has in several animal studies proved effective in treatment of microscopic 

ovarian cancer in the peritoneal cavity. In this study pharmacokinetics and 

radiotoxicity are evaluated in patients after intraperitoneal injection of 211 At- 

MX35 F(ab’)2. 

Materials: Nine patients in good remission following second-line chemotherapy 

for recurrent ovarian carcinoma participated in the study with informed 

consent. The patients underwent laparoscopy and peritoneal scintigraphy before 

the therapy. During the laparoscopy a peritoneal catheter was inserted 

and the peritoneal cavity was inspected to exclude presence of macroscopic 

tumor growth or major adhesions. The scintigraphy was made to study the 

fluid distribution in the peritoneal cavity. For the therapy, patients were infused 

with 33-172 MBq 211 At-MX35 F(ab’)2 in 1-2 L Extraneal solution via the 

peritoneal catheter. The remaining solution was drained from the peritoneal 

cavity after 24h. Gamma camera whole body scans were made at 1, 6, 12 

and 24h. All urine and samples of blood and peritoneal fluid were collected 

at 1 48h and measured for radioactivity content. 

Results: The 24h and 48h urinary excretion of 211 At was 2% and 8% respectively. 

The thyroid uptake was 1% at 24h in the first five patients. The 

following patients were effectively blocked by potassium perchlorate. No other 

organ uptake could be detected. Estimated absorbed radiation doses were: 

to bone marrow 0.08 mGy/MBq, to unblocked thyroid 15 mGy/MBq and to the 

peritoneal surface 8 mGy/MBq. No adverse effects were observed in laboratory 

parameters or subjectively. 

Conclusions: At least 150 MBq of 211 At-MX35 F(ab’)2 in 1-2L solution could 

safely be administered intraperitoneally. Extrapolation from animal data indicates 

that this activity level should result in sufficiently high absorbed doses 

to erradicate micrometastases on the peritoneum. 

754 poster 

LATE RADIATION EFFECTS TO THE RECTUM AND BLADDER IN 

GYNAECOLOGIC CANCER PATIENTS: RE-SCORING AFTER 8 

YEARS WITH LENT/SOMA AND RTOG/EORTC LATE-EFFECTS 

SCORING SCALES 

Y. Anacak 1 , Y. Bolukbasi 1 , Z. Ozsaran 1 , D. Yalman 1 , A. Aras 1 

1 EGE UNIVERSITY HOSPITAL, Radiation Oncology, Izmir, Turkey 

Purpose: In 1999 we evaluated the late effects of radiotherapy to the rectum 

and bladder in 116 gynaecological cancer patients using two different scoring 

scales (LENT/SOMA and RTOG/EORTC). The results were published in the 

red journal (Anacak et al., 2001). In this study we recalled the same patients 

after 8 years and scored the late effects using the same questionnaires. The 

purpose of this study is to evaluate radiation effects at a later period and to 

see whether there is a change by time and to check whether the correlation 

between the two scoring systems still exist after 8 years. 

Materials: All patients were treated by a combination of external irradiation 

and intracavitary HDR brachytherapy between 1988 and 1998. First evaluation 

was done in 1999 where 116 patients were participated; minimum followup 

time was 6 months. Patients were re-evaluated in 2007. There were 63 

patients in the 2nd evaluation since 20 patients died of their disease or other

easons and 33 patients were either lost to follow-up or refused to participate. 

Median follow-up time was 120 months (range 102-163). The median age 

of those 63 patients was 63 (38 to 79); diagnosis was cancer of the uterine 

cervix in 47 patients and cancer of the endometrium in 26. The total doses to 

ICRU points were as follows: bladder 55.5±4.71 Gy and rectum 55.8±3.24 

Gy. 

Results: The correlation between the two scoring scales were analysed using 

the Spearman‘s rho rank correlation test. There was a moderate correlation 

between LENT/SOMA and RTOG/EORTC scales both for rectum (r=0.69, 

p


756 poster 

MRI-BASED ASSESSMENT OF SHIFTS IN VAGINAL POSITION IN 

PATIENTS WITH GYNECOLOGICAL TUMORS AFTER HYSTEREC- 

TOMY 

M. Toet-Bosma 1 , U. van der Heide 1 , L. van de Bunt 1 , G. de Kort 2 , H. 

Schreuder 3 , I. Jurgenliemk-Schulz 1 

1 UMC-UTRECHT, Radiotherapy, Utrecht, Netherlands 

2 UMC-UTRECHT, Radiology, Utrecht, Netherlands 

3 UMC-UTRECHT, gynecology, Utrecht, Netherlands 

Purpose: An important concern in pelvic radiotherapy in patients with gynecologic 

malignancies is the considerable volume of the organs at risk (bladder, 

rectum and bowel) included in the conventional radiation fields. An approach 

to reduce the irradiated volumes of these organs and thus the risk 

of treatment-related sequelae is 3-D conformal or intensity- modulated radiotherapy 

(IMRT). However, the margins to be added to the CTV (clinical target 

volume) to generate the PTV (planning target volume) in patients who have 

undergone hysterectomy are not well defined so far. The purpose of this 

study is to define the changes in the position of the vaginal CTV’s during the 

course of radiation therapy in order to create adequate margins to generate 

the PTV’s. 

Materials: Fifteen endometrial en cervical cancer patients after hysterectomy 

were included. Each patient underwent five MRI exams on a 1.5 Tesla MRI 

scanner (weekly during the radiotherapy). Seventy-five datasets were generated. 

Vaginal CTV’s were contoured on MRI (T2 weighted slices in three 

dimensions); the inferior boundary of the CTV was defined as the caudal border 

of the symphysis. The changes in the vaginal positions relative to the 

position of the vagina on the first MRI of each patient were measured 

Results: The margins, which accommodate the changes in the position of 

the vaginal CTV on five consecutive MRI exams, are indicated in table 1. 

Conclusions: In gynecological patients after a hysterectomy we found a 

substantial shift of the position of the vagina on five consecutive MRI’s. To 

accommodate the changes in the position of the vaginal CTV an inhomogeneous 

PTV margin is needed with a maximum in the posterior dimension. 

When smaller PTV margins are chosen to profit from the use of IMRT or 3-D 

conformal treatment more specific position verification, based on the position 

of the target volume during the course of radiotherapy, is mandatory. Future 

work includes the following: (1) Defining the correlation of the shift of the 

vaginal CTV with changes in the volume of the surrounding organs at risk. 

(2) Defining position shifts of the lymphatic regions and the parametrial tissue 

on consecutive MR images and their correlation with changes in the volume 

of the organs at risk. 

757 poster 

ORGANS AT RISK DISPLACEMENTS AND THE CONSECUTIVE 

DOSIMETRIC IMPACT DURING BRACHYTHERAPY FOR CERVICAL 

CANCER 

T. Romdhani Messai 1 , I. Dumas 2 , N. Magné 1 , C. Chargari 1 , N. Gillion 1 , 

C. Haie-Meder 1 

1 GUSTAVE ROUSSY, Radiation Oncology, Villejuif, France 

2 GUSTAVE ROUSSY, Physics, Villejuif, France 

Purpose: To investigate organs at risk (OAR) displacements and the consecutive 

dosimetric impact during PDR brachytherapy for cervical cancer. 

Materials: Nine patients having PDR brachytherapy for cervical carcinoma 

were enrolled in this study. All patients were treated with external beam radiation 

therapy with concomitant chemotherapy prior to brachytherapy. The 

brachytherapy plan was applied using MRI exam. Three CT scan images 

were acquired at regular interval during brachytherapy. OAR (rectum, bladder 

and sigmoid) were delineated in each CT scan. The first part of the study 

was to investigate OAR displacement and variability. The different CT scans 

were matched together aligning bony structures. The geometrical shifts of 

the isocenter of each OAR and the volume variation were studied. The second 

part of the study was to compare the dose parameters of the OAR (D2cc 

bladder, D2cc rectum, D2cc sigmoid) when applying the same dwell positions 

and times on each CT scans. D2cc reported in this study represent only 

the brachytherapy contribution.For statistic analysis, we performed repeated 

measures ANOVA using nonparametric methods. 

Results: Organ at risk displacement: The main direction for the rectal and 

bladder isocenter displacement was into the cranio-caudal direction. The 

mean shift was 2.5 mm (SD = 4.4 mm) for the rectal isocenter and 1.6 mm 

(SD = 4.1 mm) for the bladder isocenter. The sigmoid isocenter displacement 

was mainly found into the antero-posterior direction with a mean shift of 4.3 

mm (SD = 9.6 mm). The rectal isocenter displacement between the 3 CT exams 

was statistically significant in the cranio-caudal direction (p=0.02) and the 

antero-posterior direction (p

(MF) and reviewed by the last author (JZ). Primary endpoint was local control, 

disease specific survival and late toxicity were secondary endpoints. 

Relationships between outcome parameters and prognostic and treatmentrelated 

factors were analysed using logistic regression analysis (response 

rate) or Cox Regression Analysis (local control, disease specific survival, late 

toxicity). Univariate and multivariate analyses were performed using the most 

important patient- tumour- and treatment-related factors. 

Results: The addition of hyperthermia to standard radiotherapy results in 

long-term major improvement of local control (37 to 56 %, p = 0.01) and 

survival (20 to 37 %, p = 0.03), without increasing late toxicity at 12 years 

follow-up. Local control and survival of patients treated since the trial closed 

are similar to the results of RHT-arm of the trial. In addition to commonly 

identified prognostic factors, thermal parameters incorporating both time and 

temperature have a significant influence on tumour control endpoints in multivariate 

analysis. A temperature increase of 1 0 C is expected to result in at 

least 6 % increase of chance of cure. 

Conclusions: Our results confirm previously found beneficial effects from 

adding hyperthermia to radiotherapy for patients with LACC; local control 

and survival are significantly improved compared to radiotherapy alone, the 

treatment results are consistent over time and can be reproduced in a large 

group of patients. Therefore, it is justified to offer RT+HT as an alternative 

to chemoradiation for patients with LACC for patients who are unfit to receive 

concomitant chemotherapy. The finding of a thermal dose response relationship 

can be an important stepping stone for further improvement of therapy. 

759 poster 

POINT VS VOLUMETRIC BLADDER AND RECTAL DOSIMETRY 

IN COMBINED INTRACAVITARY-INTERSTITIAL HIGH DOSE-RATE 

(HDR) BRACHYTHERAPY: CORRELATION AND COMPARISON 

WITH PUBLISHED VIENNA APPLICATOR DATA 

R. Yaparpalvi 1 , S. Mutyala 1 , N. Thawani 1 , D. Mah 1 , S. Kalnicki 1 

1 MONTEFIORE MEDICAL CENTER/AECOM, Radiation Oncology, New York, 

USA 

Purpose: We correlated rectal and bladder point and volumetric dose data 

in patients treated for advanced cervix cancers with combined intracavitaryinterstitial 

(IC+IS) high dose-rate brachytherapy (HDR BT). The results are 

compared with published Vienna applicator data 

Materials: We retrospectively analyzed 30 individual IC+IS implants from 

10 patients treated with external beam radiation therapy (EBRT) followed by 

HDR BT for locally advanced cervix carcinoma. EBRT consisted of 45 Gy to 

the pelvis followed by 9-14.4 Gy boost to the parametria. BT consisted of a 

total dose of 21 Gy delivered in 7 Gy fraction. For each implant, CT-image 

based simulation and image-guided BT treatment planning was performed. 

Bladder and rectal doses were evaluated and analyzed using both ICRU reference 

points and dose-volume histograms (DVHs). From these DVHs, minimal 

doses to highest irradiated 0.1cc, 1 cc, 2 cc, and 5 cc volumes of rectum 

and bladder were individually recorded in each case (designated as D0.1cc, 

D1cc, D2cc and D5cc respectively). The cumulative doses to the rectum 

and bladder were calculated by combining contributions from external beam 

therapy and BT. In these calculations, the dose contributions to bladder and 

rectum from parametrial boost with midline shielding were not considered. To 

facilitate comparison with published literature, the total doses were normalized 

to 2-Gy fractions (EQD2) using the equation EQD2total = EQD2EBRT+ 

EQD2BT. 

Results: The results are summarized and compared with the Vienna applicator 

study in Table 1. The dose values in Table 1 correspond to mean EQD2 

dose values averaged over the study population. The mean contoured bladder 

volume was 68 ± 22cc. The mean contoured rectal volume was 52 ± 

16cc. ICRU rectal reference dose correlated best with volumetric rectal D2cc 

dose (rS= 0.91, p=0.0003); however, the ICRU bladder dose did not correlate 

with bladder D2cc dose (rS= 0.23, p=0.50). 

Conclusions: Our study findings reveal a strong correlation between 

ICRU rectal reference dose and volumetric rectal D2cc dose in combined 

intracavitary-interstitial high dose-rate (HDR) brachytherapy. This surrogate 

rectal-dose relationship is valuable in establishing rectal tolerance dose levels 

in transitioning from traditional 2-D to image based 3-D dose planning. 


760 poster 

S 245 

POST CHEMORADIOTHERAPY STRESS FRACTURES TO THE 

PELVIS: IS IMRT THE ANSWER? 

H. Al-Booz 1 , J. Hughes 2 , A. Stapleton 3 

1 

BRISTOL HAEMATOLOGY AND ONCOLOGY CENTER, Clinical Oncology, 


2 

BRISTOL ROYAL INFIRMARY, Radiology, Bristol, United Kingdom 

3 

BRISTOL HAEMATOLOGY AND ONCOLOGY CENTER, Medical Physics, 


Purpose: We have noted an increase in the prevalence of patients presenting 

with radiologically confirmed stress fractures within 6 months of completing 

radiotherapy. We set out to study the dose delivered to radiological stress 

fractures when IMRT is substituted for conformal 3D CT planning for locally 

advanced carcinoma of the cervix. 

Materials: 30 patients treated over the past year with a radical dose of CT 

planned external beam radiotherapy (50.4 Gy/ 28 fractions/ 5.5 weeks) combined 

with weekly Cisplatin chemotherapy (40mg/m2 IV infusion). This was 

followed by three fractions of intrauterine HDR brachytherapy (13.5 Gy/ 3 fractions) 

and parametrial boost as indicated (5.4 Gy/ 3fractions/ 1.8 Gy/ fraction). 

Five patients had persistent lower back pain between three and six months 

post completion of treatment. Sacral ala stress fractures were identified on 

T1w spin echo MRI of the pelvis. We identified the area of fracture on MRI and 

correlated this with the planning CT. Isodoses were highlighted and the dose 

delivered to the area of the fracture was determined. We then re-calculated 

the isodoses using the previous planning CT as per IMRT protocol; the GTV, 

CTV and surrounding organs were delineated. Doses to the area of the fracture 

were re-examined and compared to the correlating area on the original 

plan. 

Results: Using our standard technique, the area of stress fracture received 

95% of the total dose delivered to the whole pelvis (95% of the 50.4Gy/28#) 

in two of five patients. In the three other patients the area of stress fracture 

received between 101- 103% of the total dose delivered to the whole pelvis. 

On the IMRT plans, initial analysis of the DVH’s demonstrate that the dose to 

area of stress fracture would not exceed the 88% of the total dose delivered 

to the whole pelvis. More detailed data will be presented at the meeting. 

Conclusions: IMRT will reduce the dose to the sacrum during radical radiotherapy 

to the pelvis for patients with locally advanced cervical carcinoma. 

While the sacrum is not recognized as an organ at risk in standard planning, 

the recognition of the high prevalence of these early stress fractures suggests 

that does reduction to the pelvis should be considered. 

761 poster 

QUALITY ASSURANCE FOR A PROSPECTIVE MULTI- 

INSTITUTIONAL TRIAL OF DEFINITIVE RADIOTHERAPY USING 

HIGH-DOSE-RATE INTRACAVITARY BRACHYTHERAPY FOR 

UTERINE CERVICAL CANCER: THE INDIVIDUAL CASE REVIEW 

T. Toita 1 , M. Oguchi 2 , T. Ohno 3 , S. Kato 4 , Y. Niibe 5 , T. Kodaira 6 , T. 

Kazumoto 7 , M. Kataoka 8 , N. Shikama 9 , M. Kenjo 10 , T. Teshima 11 , K.


Hayakawa 5 , Y. Kagami 12 

1 

UNIVERSITY OF THE RYUKYUS, GRADUATE SCHOOL OF MEDICAL 

SCIENCE, Radiology, Okinawa, Japan 

2 

CANCER INSTITUTE HOSPITAL, Radiation Oncology, Tokyo, Japan 

3 

GUNMA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, Department of 

Radiology and Radiation Oncology, Maebashi, Japan 

4 

NATIONAL INSTITUTE OF RADIOLOGICAL SCIENCES, Research Center for 

Charged Particle Therapy, Chiba-shi, Japan 

5 

KITASATO UNIVERSITY, SCHOOL OF MEDICINE, Radiology, Sagamihara, 

Japan 

6 

AICHI CANCER CENTER, Radiation Oncology, Nagoya, Japan 

7 

SAITAMA CANCER CENTER, Radiology, Saitama, Japan 

8 

NATIONAL SHIKOKU CANCER CENTER, Radiology, Ehime, Japan 

9 

SHINSHU UNIVERSITY, SCHOOL OF MEDICINE, Radiology, Matsumoto, 

Japan 

10 

HIROSHIMA UNIVERSITY, GRADUATE SCHOOL OF MEDICAL SCIENCE, 

Radiology, Hiroshima, Japan 

11 

OSAKA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, Department of 

Medical Physics and Engineering, Suita, Japan 

12 

NATIONAL CANCER CENTER HOSPITAL, Radiation Oncology Division, 

Tokyo, Japan 

Purpose: To assess compliance with a radiotherapy protocol of the multiinstitutional 

prospective study (JAROG0401), which investigated the efficacy 

and toxicity of definitive radiotherapy using high-dose rate intracavitary 

brachytherapy (HDR-ICBT) for patients with early stage uterine cervical cancer. 

Materials: Individual case review (ICR) of all 60 patients entered into the 

study was performed. Patient data including pretreatment MRI (T2WI), data 

of external beam radiotherapy (EBRT) (treatment chart, simulation films/ digitally 

reconstructed radiographs (DRR), portal films/ electronic portal imaging 

device (EPID) data, and dose distributions), and data of HDR-ICBT (treatment 

chart, AP/ lateral orthogonal films, and isodose distributions for all insertions) 

were collected by mail. All radiological images and dose distributions were 

digitally processed, mounted on Microsoft PowerPoint, and converted into 

CD-ROM format. Other data such as treatment charts were submitted as 

hard copies. The radiotherapy parameters reviewed were clearly stated in 

the study protocol. Protocol compliance with 16 items of radiotherapy was 

evaluated according to prearranged criteria. The data were reviewed and 

evaluated by participating radiation oncologists on the quality assurance (QA) 

committee of the JAROG. The QA committee met and performed ICR three 

times during the patient accrual period and immediately after a final patient 

entered. The ICR results of each QA committee were fed back immediately 

to the participating institutions. 

Results: Of the 60 patients (63%) evaluated, 38 were "acceptable" for all 16 

items according to the criteria. The items described by quantitative values, 

such as prescribed doses, some time intervals and overall treatment were 

well followed. The number of cases evaluated as "deviation" decreased with 

each successive QA committee meeting; 6/15 in the 1st meeting, 7/20 in the 

2nd, and 6/25 in the 3rd. Ten patients (17%) were evaluated as "deviation" 

using the method of point A determination. 

Conclusions: The present ICR demonstrated generally good radiotherapy 

protocol compliance. The decreasing number of "deviations" with each successive 

QA committee meeting suggested that the QA program could improve 

protocol compliance of radiotherapy. A dummy run or benchmark case evaluation 

might work effectively for some QA, such as point A determination, in 

future multi-institutional studies involving HDR-ICBT. 

762 poster 

RADIOTHERAPY INDUCES LONG-TERM SYMPTOMS FROM SIX 

SEPARATE REGIONS IN GYNECOLOGICAL CANCER SURVIVORS 

E. Avall-Lundqvist 1 , G. Dunberger 2 , H. Lind 2 , A. C. Waldenström 3 , M. 

Al-Abany 2 , U. Nyberg 4 , E. Onelöv 2 , G. Steineck 5 

1 

KAROLINSKA UNIVERSITY HOSPITAL, Department of Gynecologic 


2 



3 

SAHLGRENSKA UNIVERSITY HOSPITAL, Department of Gynaecological 

Oncology, Göteborg, Sweden 

4 

ST GORAN HOSPITAL, Section of Psychiatry, Stockholm, Sweden 

5 

KAROLINSKA INSTITUTET/SAHLGRENSKA ACADEMY, Department of 

Clinical Cancer Epidemiology, Stockholm/Gothenburg, Sweden 

Purpose: A patient-reported inventory of radiotherapy-induced symptoms 

among long term gynecological cancer survivors is lacking. 

Materials: Eight hundred and sixty-nine women, who had been treated with 

radiotherapy for a gynecological cancer during 1991 to 2003 at two Departments 

of Gynaecological Oncology in Sweden, participated in a populationbased 

study. A control group of 480 women from the Swedish Population 

Registry, matched for age and regional residence, was also included. In 

preparation, we made in-depth interviews with 26 women with a history of 

gynecological cancer. Based on their experience, we constructed a questionnaire, 

including 351 questions and validated face-to-face with 20 individuals. 

The women answered the questions covering experienced physical symptoms 

from the bowel, anal sphincter, urinary and genital tract, the skeleton 

as well as lower abdomen and legs. The questionnaire also covered demographical, 

psychological and quality of life questions 

Results: Response rate was 79% for cancer survivors and 72% for control 

women. Mean follow-up was 7.8 years. The highest relative risk (RR) was 

found for unexpected defecation in clothing (RR 20.9; 95% CI 6.0-72.2), protracted 

genital pain (RR 11.3; 95% CI 3.7-33.9), loose stools while asleep (RR 

9.9; 95% CI 4.4-22.4) and pain from sacrum when walking indoors (RR 9.0; 

95% CI 5.0-16.0). Vomiting with abdominal pain (RR 4.0; 95% CI 1.8-8.7), 

difficulty feeling when bladder is full (RR 4.0; 95% CI 2.1-7.5) and protracted 

leg pain (RR 2.0; 95% CI 1.4-2.9) were symptoms also strongly associated 

with radiotherapy. 

Conclusions: Pelvic radiotherapy is related to long-term symptoms from all 

studied regions namely the bowel, anal sphincter, urinary and genital tract, 

skeleton as well as lower abdomen and legs 

763 poster 

RECURRENT ENDOMETRIAL CARCINOMA: RESULTS AFTER 

SALVAGE RADIOTHERAPY WITH HDR BRT ALONE OR IN COMBI- 

NATION WITH EBRT 

S. Gribaudo 1 , E. Madon 1 , U. Monetti 1 , A. Mussano 1 , V. Richetto 1 , A. 

Sardo 1 , A. Urgesi 1 

1 A.O. OIRM-S.ANNA, Radiotherapy, Turin, Italy 

Purpose: To evaluate the efficacy, long-term disease control, survival and 

complication rates of high dose rate brachytherapy (HDR BRT) alone or in 

combination with external beam radiotherapy (EBRT) in the treatment of patients 

with local recurrences of adenocarcinoma of the endometrium. 

Materials: From 1997 to 2006 107 pts with vaginal or pelvic recurrence of endometrial 

carcinoma were treated; 89 endometrioid (83.2%). Mean age at the 

recurrence 73 (41-87). Mean time to relapse was 33 months (range 3-122). 

Symptoms were: vaginal bleeding 35 (32.7%), vaginal bleeding and abdominal 

pain 29 (27.1%), abdominal or back pain 33 (30.8%); 10 patients (9.3%) 

were asymptomatic. Staging with the Perez modified FIGO for primary vaginal 

carcinoma: 35 pts Stage I (32.7%), 62 Stage II (57.9%), 5 Stage III (4.7%), 

5 Stage IV (4.7%). Primary treatment: 81 (75.7%) surgery alone, 14 (13.1%) 

surgery plus EBRT, 9 (8.4%) surgery plus CTH, 3 (2.8%) RT alone.HDR BRT 

was used in 96 pts (93 intracavitary and 3 interstitial) in 35 cases BRT HDR 

alone, in 61 was combined with EBRT. EBRT doses from 30.6 to 66.6 Gy. 

Intracavitary HDR BRT doses from 15 to 25 Gy in combination with EBRT 

and from 30 to 55 Gy when used alone; fraction size 5-6 Gy. Prescriptions 

for intracavitary therapy were at depths ranging between 5 and 10 mm, according 

with the lesion size and 3-4 fractions/week were used. Intracavitary 

vaginal applicators was used: vaginal cylinders, vaginal shielded cylinders, 

vaginal Miami applicator and vaginal ovoids. EBRT: 6 MV photons AP-PA 

and 4 fields box technique; a central lead shield was used in the last part of 

EBRT in the 25% pts and in some cases (bulky disease, previously irradiated 

pts) was used with a DMLC collimator. 

Results: Median follow-up was 75 months (range 18-132). CR was achieved 

in 99 pts (92.5%). The 5-year overall survival were: 82.4% in Stage I, 55.2% 

in Stage II, 60.6% in Stage III and 40% in Stage IV. The 5-year DFS were 

80% in Stage I, 51.7% in Stage II, 54.1% in Stage III and 40% in Stage IV. 

Median time to relapse in the 14 local recurrences was 15 months (range 6- 

47); 6 of these pts have been retreated with further HDR intracavitary BRT 

and 4 achieved a new complete response. The late complications were scoring 

according to the Franco-Italian Glossary, in 55% pts there were no late

complication. Affected organs included vagina 43.9% (26.1% G1 11.2% G2 

6.5% G3), bladder 17.7% (9.3% G1 8.4% G2 no G3) and rectum 19.6% 

(7.5% G1 11.2% G2 1% G3); two pts developed a severe necrosis of the 

mucosa of the inferior third of the vagina which resolved after medical therapy. 

Conclusions: Treatment of local recurrences of endometrial adenocarcinoma 

with HDR BRT alone or in combination with EBRT is effective. Factors 

determining treatment outcome were relapse Stage (I-IIA), association 

of EBRT and HDR BRT, total dose. HDR BRT alone if the staging of relapses 

is correct is efficacy and safe. Second salvage HDR BRT is possible. Severe 

complications are rare even in pre-irradiated pts. 

764 poster 

RESULTS OF PILOT STUDY WITH USE PET (18FDG) IN RADIO- 

THERAPY TREATMENT PLANNING IN PATIENTS WITH CERVIX 

CARCINOMA 

H. Dolezelova 1 , P. Slampa 2 , B. Ondrova 2 , J. Gombosova 2 , T. Novotny 2 , 

J. Ruzickova 2 , J. Garcic 2 , L. Hynkova 2 , H. Soukalova 2 

1 MASARYK MEMORIAL CANCER INSTITUTE AND MEDICAL FACULTY 

MASARYK UNIVERSITY, Radiation Oncology, Brno, Czech Republic 

2 MEMORIAL CANCER INSTITUTE AND MEDICAL FACULTY MASARYK 

UNIVERSITY, Radiation Oncology, Brno, Czech Republic 

Purpose: Positron emission tomography (PET) is a complementary method 

to determine target volumes in radiotherapy. Daily using of PET in the oncology 

praxis can change treatment strategy and improve its outcome. Results 

of this pilot study show the role of PET with 18F-fluorodeoxyglicose (18FDG) 

in staging of cervical carcinoma and in the radiotherapeutic planning. 

Materials: Between March 2005 and May 2007, 51 patients with cervical 

carcinoma were treated with combination of external beam radiotherapy and 

HDR brachytherapy (uterovaginal application; 4-5 fractions), with or without 

concomitant cisplatin. The lymphatic nodes treatment field size was determined 

by PET/CT fusion. We used standard regime of radiotherapy: 5x1.8 

Gy/fractions/week. The upper board of radiation field depends on lymph 

involvement: in case no lymph involvement the upper board was in L4/5; 

with involved illiac nodes or paraaortic nodes the upper board was moved 

to Th12/L1. Treatment results were evaluated by PET 3 and 9 months after 

treatment. 

Results: The difference in the results of PET and CT was evaluated in this 

study. In 32 cases (62.7%) the results of PET and CT were identical, in 14 

cases (27.5%) the nodal involvement was more extensive according to PET, 

in 5 cases (9.8%) the nodal involvement was more extensive according to 

CT. PET results 3 months after treatment were as follows: in 3 cases (5.9%) 

stable disease, in 35 cases (68.6%) negative, in 4 cases (7.8%), progression 

of disease, in 3 cases (5.9%) partial regression. There should not occur any 

false positive results caused by inflammatory reaction persisting 3 months 

after radiotherapy, as was confirmed by repeating PET 9 months after treatment. 

Conclusions: The results of this study confirmed the important role of PET in 

diagnosis and treatment of cervical carcinoma and in determination of target 

volumes in radiotherapy. PET was found to be a standard staging examination 

of cervical carcinoma in Masaryk Mem. Cancer Inst. The predictive value of 

PET has not yet been validated. THIS STUDY WAS SUPPORTED BY THE 

RESEARCH GRANT IGA MZ CR NR/8322-3 

765 poster 

RESULTS OF POSTOPERATIVE RADIOTHERAPY IN THE TREAT- 

MENT OF UTERINE SARCOMAS: A RETROSPECTIVE ANALYSIS 

OF 46 PATIENTS 

D. Yalman 1 , Z. Ozsaran 1 , B. Baltalarli 2 , O. Demir 3 , A. Aras 1 

1 

EGE UNIVERSITY FACULTY OF MEDICINE, Radiation Oncology, Izmir, 

Turkey 

2 

PAMUKKALE UNIVERSITY FACULTY OF MEDICINE, Radiation Oncology, 

Denizli, Turkey 

3 

ATATURK STATE HOSPITAL, Radiation Oncology, Izmir, Turkey 

Purpose: The aim of this study is to evaluate the treatment outcome, survival 

data and prognostic factors in patients with uterine sarcoma treated by 

postoperative radiotherapy. 

Materials: Records of 46 patients treated between 1993-2003 were reviewed. 

Median age was 55 (range 31-75). There were 21 mixed mullerian 

tumors, 12 leiomyosarcomas, 11 endometrial stromal sarcomas and 2 

adenosarcomas. According to FIGO classification 65.2% were Stage I, 17.4% 

Stage II, 13% Stage III and 4.3% Stage IV. All patients received external radiotherapy 

with 1.8 Gy daily fractions up to 50.4-64 Gy (median 50.4 Gy). 

Intracavitary brachytherapy was applied to 39 patients. Twelve patients received 

adjuvant chemotherapy. 

Results: Median follow-up time was 48 months (6-144 months). Seventeen 

patients (37%) developed distant metastases and one patient had local 

failure. Five-year overall, disease-free and local recurrence-free survival 

rates were 57.8%, 60.5% and 97.8% respectively. Univariate analysis 

demonstrated that stage (p=0.011), histologic subtype (p=0.010), tumor 


S 247 

size (p=0.044), and positive peritoneal cytology (p=0.006) and the use of 

chemotherapy (p=0.005) had a significant effect on overall survival. Prognostic 

factors influencing disease-free survival were stage (p=0.009), positive 

peritoneal cytology (p=0.000) and the use of chemotherapy (p=0.002). The 

only prognostic factor affecting local control was stage (p=0.000). 

Conclusions: Postoperative radiotherapy seems to be an effective adjuvant 

treatment providing high local control rates in uterine sarcomas. However 

its efficacy should be clarified by randomized trials. The important prognostic 

factors influencing the treatment results were stage, histologic subtype, tumor 

size and positive peritoneal cytology. 

766 poster 

RESULTS OF TREATMENT IN PATIENTS WITH STAGE I ENDOME- 

TRIAL CARCINOMA 

G. K. Rath 1 , D. Sharma 1 , K. Milind 1 , P. Julka 1 , A. Bahl 1 , K. Haresh 1 , S. 

Kumar 1 

1 ALL INDIA INSTITUTE OF MEDICAL SCIENCES, Radiation Oncology, 

NewDelhi, India 

Purpose: The aim of this study was to analyze the results of treatment in 

patients with stage I endometrial carcinoma. 

Materials: The study population consisted of 70 patients who underwent 

surgery and found to have FIGO stage I endometrial carcinoma. The surgical 

procedure followed was total abdominal hysterectomy (TAH) plus bilateral 

salpingo oopherectomy (BSO) with or without lymph node sampling. The policy 

of adjuvant treatment was as follows: stage IA, Grade 1-2, no adjuvant 

treatment; Stage IA grade 3, IB grade 1-2; intravaginal brachytherapy (IVBT) 

alone; stage IB grade 3, IC grade 1-3; pelvic external beam radiotherapy 

(EBRT) combined with IVBT. The dose of IVBT was 7 Gy x 3 fractions (high 

dose rate, once a week fraction) prescribed at 0.5 cm from the surface of intravaginal 

applicator. The length of vagina treated was 3-5 cm. The dose of 

IVBT, when combined with EBRT, was 6 Gy x 2 fractions. Pelvic EBRT dose 

was 5040 cGy in 28 fractions over 5.5 weeks with conventional fractionation 

schedule. Pelvic control rate, overall survival and late toxicity (RTOG criteria) 

were determined in different substages. 

Results: The age of the patients ranged from 23-76 years (median 54 years). 

The distribution of the stage and grade was as follows: IA GI, 5; IA G2, 0; IA 

G3, 2; IB G1, 29; IB G2, 5; IB G3, 8; IC G1, 8; IC G2, 6; and IC G3, 7 patients. 

Of 70 patients, 62 (89%) had pelvic disease control. The 5 year projected 

survival was 76%. The severe late radiation related morbidity (RTOG grade 

3-4) was 6%. 

Conclusions: Our policy of adjuvant treatment in stage provides excellent 

disease control and survival with minimal long term toxicity. 

767 poster 

ROLE OF VARIOUS METHODS OF BRACHYTHERAPY IN CARCI- 

NOMA OF VAGINA 

S. Kucucuk 1 , B. Sarper 2 , I. Aslay 1 , G. Kemikler 3 , I. Ozbay 3 , M. Dincer 1 , 

S. Berkman 4 , Y. Eralp 5 , R. Disci 6 , G. Tore 1 

1 

ISTANBUL UNIVERSITY ONCOLOGY INSTITUTE, Radiation Oncology, 

Istanbul, Turkey 

2 

KOCAELI UNIVERSITY MEDICAL SCHOOL, Radiation Oncology, Kocaeli, 

Turkey 

3 

ISTANBUL UNIVERSITY ONCOLOGY INSTITUTE, Medical Physics, Istanbul, 

Turkey 

4 

ISTANBUL UNIVERSITY ISTANBUL MEDICAL SCHOOL, Department of 

Gynecology and Obstetrics, Istanbul, Turkey 

5 

ISTANBUL UNIVERSITY ONCOLOGY INSTITUTE, Medical Oncology, Istanbul, 

Turkey 

6 

ISTANBUL UNIVERSITY ISTANBUL MEDICAL SCHOOL, Department of 

Biostatistics, Istanbul, Turkey 

Purpose: To analyze the impact of the total doses of irradiation, biological 

equivalent dose (BED) and brachytherapy techniques on treatment results in 

patients treated with definitive radiotherapy for carcinoma of the vagina. 

Materials: Fifty patients with carcinoma of the vagina who received radiation 

therapy were reviewed, retrospectively. Forty two patients (84%) were treated 

with a combination of external beam irradiation (EBRT) and brachytherapy, 

and 8 (16%) were treated with EBRT only. Fifteen patients (36%) received 

high dose rate (HDR), 27 (64%) received low dose rate (LDR) brachytherapy. 

Results: With a median follow-up of 42 months, 24 patients (48%) were recurred 

locally. The local recurrence rates (LRR) in patients treated with EBRT 

alone, EBRT and HDR brachytherapy, EBRT and LDR brachytherapy were 

88%, 60% and 29%, respectively. Although overall survival was similar in 

LDR and HDR group (47.6%, 41.8%, respectively), local disease free survival 

(LDFS) was higher in LDR group than in HDR group (60.2%, 33.3%, 

respectively). LRR were decreased from 63% to 30.4% when total dose exceeds 

70 Gy , 55.8% to 25% when BED value exceeds 80 Gy. Response 

to EBRT, brachytherapy, total dose and BED values were significant factors 

in LDFS on univariate analysis, brachytherapy and tumor dimension (>4 cm) 

were the prognostic factors on multivariate analysis.


Conclusions: Definitive radiotherapy is the treatment choice for the patients 

with vaginal carcinoma. Optimal outcomes can be achieved with adequate 

dose delivery. Brachytherapy, which can be individualized to cover the target 

volume, plays an effective role in this treatment. 

768 poster 

STANDARD BONY LANDMARK-BASED SUPERIOR BORDER IS 

NOT RELIABLE FOR RADIATION TREATMENT IN PATIENTS WITH 

CERVICAL CANCER 

B. Santamaria Torruco 1 , D. Vilar Compte 2 , M. Rodríguez Ponce 1 , F. 

Herrera Martínez 1 , A. Calvo Fernandez 1 , A. Poitevin Chacon 1 

1 

INSTITUTO NACIONAL DE CANCEROLOGIA, Department of Radiation 

Oncology, D.F., Mexico 

2 

INSTITUTO NACIONAL DE CANCEROLOGIA, Department of Infectious 

Diseases, D.F., Mexico 

Purpose: The purpose of this study was to evaluate whether the pelvic-field 

superior border for cervical cancer based on bony landmarks set up in the 

intervertebral space between L4 and L5 adequately covers the common iliac 

nodal group within the treatment volume of 3D-stimulated patients. Additionally, 

we registered bony landmark-based aorta location and measured from 

intervertebral space between L4-L5 to aortic bifurcation and the distance from 

vertebral space between L4-L5 to optimal coverage limit in which common iliac 

nodes were included. We also estimated whether there was a correlation 

between patient height in Mexican population and bifurcation location. 

Materials: We included patients with uterine cervical cancer stages IBIVA 

and patients who had undergone surgery for their primary disease who presented 

high risk factors (positive margins, vascular and lymphatic permeation, 

pelvic node invasion) and who had not been treated previously with radiotherapy. 

Computed tomography simulation was used with patients in prone 

position using 0.5-cm slices. Planning was with Eclipse system. Images were 

reconstructed to identify aortic bifurcation location, as well as optimal location 

of treatment volume coverage to correlate this with anatomic bony landmarks. 

Adequate planning volume was defined as 1.5 cm above the bifurcation of the 

aorta covered with isodose curve of +5 to 7% and was considered inadequate 

when the distance was >1.5 cm. Distance from L4L5 vertebral space to the 

bifurcation was measured in cm, and was also measured 1.5 cm above this 

landmark to determine optimal treatment volume-coverage distance. Patient 

height measured in cm was correlated with the aortic bifurcation location. 

Results: 101 patients with uterine cervix cancer were included. Mean age 

was 48 ± 4 years. Patient clinical stage: IBI, 6 (5.9%); IB2, 4 (4.0%); IIA, 1 

(1.0%); IIB, 47 (46.5%); IIIA, 2 (2%); IIIB, 24 (23.8%);stage IVA 2 (2.5%), and 

14 (13.9%) were operated on with high risk factors. Optimal limit setup coverage 

was suitable in 21 (20.8%) of patients. Optimal distance to coverage: 

median was 3.0 cm (0.06.9 cm). In 85, 90, and 95 percentile: 4.5, 5.0, and 

5.6 cm. Anatomic bony landmark-based optimal location (Figure 1) was: If 

the treatment border was placed at L4/L5 interspace, only 5% of cases was 

covered, while this was 35.6% if placed in mid-L4, 77.2% at L4-L3 interspace, 

94.1% in mid-L3, while if placed at L2-L3 interspace, 100% was covered. Relationship 

between patient size and bifurcation location. Mean patient height 

was 150 cm (140173 cm) and was correlated with the aortic location. Spearman 

rank correlation was performed with 0.193 as coefficient of association 

with p

Results: For treatment-related bladder morbidity, the highest incidence 

was observed for cystitis (39%), and the lowest incidence for urine incontinence 

(22%). No significant differences were found between the two treatment 

groups. The analysis showed that CTCAE-cystitis, CTCAE-bladder, 

CTCAE-incontinence and CTCAE-enteritis were all significantly associated 

with HRQoL in general. More specifically, all grade 2-4 radiation-induced urinary 

tract toxicity had a large impact on the general dimensions of HRQoL, 

such as on physical, role, emotional and social functioning as well as on 

global QoL. Similar results were found for CTCAE-enteritis. 

Conclusions: The addition of concomitant CHT to RT did not result in an increased 

risk of late radiation-induced sides effects. However, urinary tract and 

intestinal side effects are found in a relatively large proportion of patients, and 

have a major negative impact on HRQoL. The results of this study stresses 

the importance of prevention of these side effect, e.g. by using advanced and 

imaging guided radiation delivery techniques. 

771 poster 

VESICAL INSTILLATIONS OF HYALURONIC ACID REDUCE 

THE ACUTE VESICAL TOXICITY INDUCED BY HIGH DOSE 

BRACHYTHERAPY 

A. Rodriguez Perez 1 , P. M. Samper Ots 1 , M. C. Lopez Carrizosa 2 , J. M. 

Delgado Perez 2 , A. Sotoca Ruiz 2 

1 

HOSPITAL CENTRAL DE LA DEFENSA GOMEZ ULLA, Radiation Oncology, 

Madrid, Spain 

2 

HOSPITAL CENTRAL DE LA DEFENSA, Radiation Oncology, MADRID, Spain 

Purpose: To determine whether the intravesical use of hyaluronic acid (HA) 

reduces acute and late vesical toxicity induced by radiotherapy. 

Materials: Single-centre retrospective study of patients diagnosed with cervical 

and endometrial cancer treated between September 2002 and November 

2007 with brachytherapy (BT) with or without intravesical instillation of 

HA. Patients were assigned consecutively to the two treatment groups (HA or 

non-HA). Forty mg of HA was instilled intravesically for approximately 30 minutes 

prior to each BT session. Rates of acute and late vesical toxicity were 

recorded in the two groups using the RTOG criteria. 

Results: Ninety-five clinical histories of patients treated with BT were reviewed 

(48 with HA instillation and 47 without). The diagnoses were cervical 

cancer (28.4%), endometrial cancer (70.5%) and vaginal cancer (1.1%). 

Surgery had been administered in 85.3% of cases, external radiotherapy in 

76.8%, and chemotherapy in 25.3%. There were no significant differences 

between the HA group and the non-HA group with regard to the total number 

of BT sessions (mean: 5.0 vs 4.9, n.s.), dose per session (mean: 478.13 vs 

505.32 cGy; n.s.), total dose (mean: 24.02 vs 24.86 Gy; n.s.) or biological 

equivalent dose (mean: 35.59 vs 37.82; n.s.). In all the sessions the percentage 

of patients presenting acute vesical toxicity was lower in the HA group 

(p

S 250 CLINICAL/DISEASE SITES : HEAD AND NECK 

774 poster 

ACUTE TOXICITY AND RESPONSE TO INDUCTION CHEMOTHER- 

APY AND CONCOMITANT HYPOFRACTIONATED RADIOTHERAPY 

IN LOCALLY ADVANCED ORAL CANCER 

A. Jamshed 1 , R. Hussain 2 , M. Fareed 1 , M. Ali 1 , I. Haider 1 , S. Hameed 

1 , M. Shah 1 , U. Majeed 1 , R. Azhar 3 , Q. Ahmed 3 

1 

SHAUKAT KHANUM MEMORIAL CANCER HOSPITAL, Radiation Oncology, 

Lahore, Pakistan 

2 

SHAUKAT KHANUM MEMORIAL CANCER HOSPITAL, Surgery, Lahore, 

Pakistan 

3 

SHAUKAT KHANUM MEMORIAL CANCER HOSPITAL, Pathology, Lahore, 

Pakistan 

Purpose: Survival in locally advanced squamous cell carcinoma of the oral 

cavity (SCCOC) is poor with standard treatment. We evaluated acute toxicity, 

response and short term survival to a newer regime of induction chemotherapy 

followed by concomitant hypofractionated radiotherapy (CHypoRT) in locally 

advanced SCCOC. 

Materials: Between June 2005 and July 2007, 48 patients with locally advanced 

SCCOC were treated with induction chemotherapy and CHypoRT in 

our institution. Male 69%:Females 31%. Site of disease: tongue 17 (35%), 

buccal mucosa 20 (42%), lower alveolus 4 (8%), upper alveolus 1 (2%), retromolar 

trigone 5 (11%) and hard palate 1 (2%) patient. Seven patients (15%) 

had AJCC stage III and 41 (85%) patients had stage IV disease. Induction 

chemotherapy was cisplatin 75 mg/m2 day 1 and gemcitabine 1000 mg/m2 

day 1 and 8. Primary tumour and nodal metastases were irradiated with 2.75 

Gy once a day, 5 days a week to a median tumour dose of 55 Gy with concurrent 

cisplatin 75 mg/m2 day 1 and 22. Spinal cord dose was limited to 30.2 

Gy. Percutaneous endoscopic gastrostomy (PEG) was placed in 31 patients 

(65%). Toxicity was assessed at weekly intervals during radiation therapy and 

response at 6 weeks following completion of treatment. Toxicity was scored 

according to common toxicity criteria. 

Results: Induction chemotherapy was well tolerated with no grade 3 4 

haematological, hepatic or renal toxicity. Response to induction chemotherapy 

was CR in 22 (46%) and PR in 26 (54%) patients. Overall response 

to induction chemotherapy was 100%. Severe acute toxicity related to CHypoRT: 

oral mucositis grade 3-4 in 8 (17%), severe oral pain grade 2 in 2 (4%), 

dehydration grade 3 in 1 (2%) and febrile neutropenia in 2 (4%) patients. 

Treatment delay due to acute radiation toxicity: < 1 week in 10 (21%) and 

more than 1 week in 2 (4%) patients. Tumour response to CHypoRT was CR 

in 36 (75%) and persistent disease in 12 (25%). Kaplan Meier estimate of 

overall survival and disease free survival at 2.4 years was 70% (95%CI:1.76 

2.32) and 34% (95%CI: 0.86-2.18) respectively. 

Conclusions: Gemcitabine cisplatin has a high response rate in untreated 

SCCOC. Acute toxicity and response to CHypoRT are comparable to more 

conventional treatment regimens used in oral cavity cancer. It has the added 

advantage of short duration and economic feasibility and merits evaluation in 

controlled trials against standard treatment regimes. 

775 poster 

ADAPTIVE 18F-FDG-PET-BASED DOSE PAINTING BY NUMBERS 

FOR HEAD AND NECK CANCER ? THE FIRST RESULTS OF PHASE 

I DOSE ESCALATION STUDY 

I. Madani 1 , C. Derie 1 , B. Vanderstraeten 1 , M. Coghe 1 , W. De Gersem 1 , 

W. De Neve 1 


Purpose: to investigate feasibility and to measure acute and dose-limiting 

toxicity (DLT) when we performed phase I dose escalation study using 

adaptive 18 F-FDG-PET-based dose painting by numbers ( 18 F-FDG-PET-voxel 

intensity-based IMRT) for head and neck cancer. 

Materials: Between February and June 2007, 7 patients with squamous cell 

carcinoma of the oro-, hypopharynx and oral cavity were treated with adaptive 

18 F-FDG-PET-voxel intensity-based IMRT. All patients but 2 received concomitant 

platinum-based chemotherapy. The dose was "painted" by numbers 

in the clinical target volume (CTV) in 2 consecutive periods followed by conventional 

IMRT to the median dose 80.92 Gy (Figure 1). Period I (10x2.5 

Gy) was based on pre-treatment 18 F-FDG-PET/CT. After the first 8 fractions 

per-treatment 18 F-FDG-PET/CT was performed. Adapted targets, organs at 

risk and the treatment plan were used for period II (10x3.0 Gy). Conventional 

IMRT (12x2.16 Gy) was based on per-treatment 18 F-FDG-PET/CT. Methodology 

of 18 F-FDG-PET-voxel intensity-based IMRT was described previously 

[1]. 18 F-FDG-PET-voxel intensity-based IMRT was delivered using daily conebeam 

CT set-up. Rigid registration of pre- and per-treatment CT- and 18 F- 

FDG-PET-images was used for plan summation. Acute toxicity was scoring 

using CTC v.2. DLT was defined as any Grade 4 toxicity observed during 

radiotherapy and up to 3 months after treatment end. 

Results: Adaptation of the targets reduced the volume of the gross tumor 

volume from 12.5±16.2 (period I) to 5.3±7.2 cc (period II); the CTV: from 

73.1±47.3 (period I) to 61.8±46.5 cc (period II). D2, D50 and D98 in the 

CTV for the whole treatment were 83.6±2.3, 78.9±4.4 and 70.8±7.2 Gy respectively. 

D50 in the PTV and elective neck: 77.6±4.9 and 45.2±0.9 Gy re- 

spectively. Treatment plan adaptation resulted in decrease in the dose to the 

spinal cord: D2 and D50 were 38.8±5.1 and 20.6±8.3 Gy correspondently. 

The mean Q-factor, a measure of the obtained dose over the intended dose, 

of 18 F-FDG-PET-voxel intensity-based IMRT treatment plans was 3.6±2.3% 

at the planned 5%. All 7 patients completed treatment with no evidence of 

disease at 3 months follow-up. No DLT was observed. Grade 3 acute dysphagia 

was detected in 5 patients, mucositis - 2 patients and 1 had grade 3 

dermatitis. Of 6 patients receiving percutaneous gastrostomy (PEG), 2 were 

PEG-dependent at 6 months follow-up. One patient without PEG required 

esophagus dilatation at 3 months, another one developed mucosal ulceration 

inside the CTV at 6 months follow-up. 

Conclusions: Adaptive 18 F-FDG-PET-voxel intensity-based IMRT of head 

and neck cancer is feasible. Acute toxicity appears tolerable. Adaptive approach 

allows reducing the volumes and doses to organs at risk. References:1. 

Radiother Oncol 2006;79:249-58. 

776 poster 

ADENOID CYSTIC CARCINOMA (ACC) OF THE NASOPHARYNX 

(NP) : 5 NEW CASES PRESENTATION, NON-SURGICAL MANAGE- 

MENT AND LITERATURE REVIEW 

O. Chan 1 , M. Lei 1 , M. E. A. O’Connell 1 , M. Gleeson 2 , R. Simo 3 

1 

GUY’S AND ST THOMAS’ NHS FOUNDATION TRUST, Clinical Oncology, 


2 

GUY’S AND ST THOMAS’ NHS FOUNDATION TRUST, Department of 

Otorhinolaryngology Skull Base Surgery, London, United Kingdom 

3 


Otorhinolaryngology, London, United Kingdom 

Purpose: Adenoid cystic carcinoma (ACC) of the nasopharynx (NP) is very 

rare with about 50 cases described in the World literature. We report 5 additional 

patients. 

Materials: From 1974 to 2007, 5 patients with biopsy proven nasopharyngeal 

ACC were treated. We report their clinical course. 

Results: Case1 59 year old male presented with weight loss,headache, epistaxis 

and bone pain. Nasendoscopy and CT scans revealed extensive tumour 

involving the skull base. Bone scan showed rib and pelvic metastases (Stage 

lVC, AJCC 2007). He received radiotherapy (RT) 65Gy to the NP and 30Gy 

to the pelvis but died 10 months later with progressive disease. Case 2 29 

year old female presented with headache and diplopia. CT scan showed disease 

involving the sphenoid sinus (Stage lVA). She received RT 65Gy with 

Epirubicin/Cisplatin chemotherapy. 12 months later disease recurred in the 

cavernous sinus and she received stereotactic RT 12Gy. She relapsed and 

died 54 months from diagnosis with local recurrence. Case 3 46 year old 

male presented with rhinosinusitis. Nasendoscopy revealed tumour arising 

from the NP and MRI scan showed infiltration of the maxillary antrum,nasal 

cavity,pterygopalatine fossa with ipsilateral level 2 nodes (Stage lVA). He received 

RT 65Gy and is well at 16 months. Case 4 52 year old male presented 

with headache and epistaxes. MRI showed disease from post-nasal 

space involving skull base and cavernous sinus (Stage lVB). He received RT 

65Gy with good partial response and is alive at 12 months. Case 5 71 year 

old female presented with epistaxis,anorexia and weight loss. MRI confirmed 

tumour from NP involving skull base,orbit,pterygopalatine fossa with intracranial 

extension and bilateral neck nodes. CT showed lung metastases (Stage 

lVC). She received palliative care and died 6 months later. 

Conclusions: Literature review shows that the time from first symptom to 

treatment ranges from 2 weeks to 5 years (median 24 months). Patients 

present with insidious onset of facial pain, epistaxis,diplopia and hearing loss. 

Compared with undifferentiated squamous carcinoma, ACC of the NP has a 

higher incidence of cranial nerve involvement (55%) and a lower incidence 

of cervical lymphadenopathy (15%). The 5 and 10 year overall survivals reported 

are 78% and 50% respectively. Despite radical local therapy the outcome 

is poor. 

777 poster 

ADVERSE SKIN REACTIONS DURING HIGH.DOSE RADIOTHER- 

APY PLUS CETUXIMAB IN LOCALLY ADVANCED HEAD AND NECK 

CANCER: A THERAPEUTIC APPROACH 

F. Miccichè 1 , V. Valentini 1 , N. Dinapoli 1 , R. Autorino 1 , M. Balducci 1 , P. 

Bonomo 1 , B. De Bari 1 , M. De Santis 1 , S. Lanza Silveri 2 , C. Guerriero 2 , 

R. Capizzi 2 

1 CATHOLIC UNIVERSITY, Department of Radiotherapy, Rome, Italy 

2 CATHOLIC UNIVERSITY, Department of Dermatology, Rome, Italy 

Purpose: To evaluate the effect of dematologic counselling on cutaneous 

toxicity and on radiotherapy treatment interruptions in patients undergoing 

radiation therapy plus cetuximab for advanced head and neck cancer. Skin 

reactions are one of the most frequent adverse events during this therapy. 

Materials: Patients with advanced squamous-cell carcinoma of the oropharynx, 

hypopharynx and larynx, ECOG 0, no undergone previous chemotherapy 

(CHT) or RT were enrolled . Before the start of RT plus Cetuximab and 

once a week patients received dermatologic evaluation. Toxicity was eval-

uated weekly according to CTC v3.0. Treatment consisted of high.dose RT 

plus weekly cetuximab at an initial test of 20 mg/mq to test the tolerability, 

followed by a loading dose of 400 mg/mq one week before radiotherapy and 

then a dose of 250 mg/mq weekly for the duration of radiotherapy. The control 

group (15 patients) received dermatologic visit on demand only after a severe 

skin reaction. 

Results: A total of twenty patients underwent at pre-treatment dermatologic 

evaluation and a strict dermatologic monitoring once a week , indipendently 

from the severity of the reaction. They have been also subjected to standardized 

treatement according to skin toxicity, while the control group (15 

patients) has been subjected to dermatologic visit required by the radiotherapy 

clinicians only after a severe skin reaction. The interruption’s mean was 

12.6 days (range 0-28 days) and the 8/15 pts had an interruption > 8 days 

in the control group. The major cause of interruption in this group was skin 

toxicity of grade 3-4 (60%). The costant therapy of cutaneous-mucous adverse 

events of patients of second group, based on the toxicity grade, has 

permitted a better control of dermatologic synthoms in the patients put under 

a strict monitoring of clinic manifestations. 

Conclusions: The costant therapy of cutaneous-mucous adverse events of 

these patients, based on the toxicity grade, has permitted a better control of 

dermatologic synthoms in the patients put under a strict monitoring of clinic 

manifestations. The preliminary results seems that a rapide and serious examination 

of these patients prevents the rise of cutaneous-mucous reactions 

and guarantees a better quality of life and, at the same time, the reduction of 

interruptions of radiotherapy treatment. 

778 poster 

ASSESSMENT OF DOSE TO BREAST TISSUE DURING HEAD AND 

NECK CANCER RADIATION THERAPY 

S. Both 1 , J. Novak 1 , P. Dutta 1 , A. Kassaee 1 , V. Bar Ad 1 

1 UNIVERSITY OF PENNSYLVANIA, Department of Radiation Oncology, 

Philadelphia PA, USA 

Purpose: For more then a decade IMRT combined with 3D techniques were 

employed by many institutions. IMRT techniques can treat the primary site 

and entire lymphatic drainage while critical structures can be spared, avoiding 

the dose uncertainty at match lines with traditional 3D techniques. However 

the combination of IMRT with AP or AP/PA supraclavicular half beam block 

(HBB) techniques are widely used by many institutions as one of the concerns 

is that we are treating a larger volume of normal tissue irradiated at a 

lower radiation dose when IMRT is used as compared to conventional radiotherapy. 

We investigated the dose at breast level outside of the treatment field 

when IMRT alone is used or when used in combination with conformal techniques, 

as secondary malignancies at breast level are of concern, especially 

for young women. 

Materials: The volumes simulating a head and neck cancer were outlined 

on a female RANDO phantom and planned with (i) IMRT and AP HBB field 

with a low match line, (ii) IMRT and AP/PA fields with a high match line and 

(iii) IMRT only. A separate (iiii) IMRT plan was generated with the HRCTV 

extended to superclav level for outside-of-field dose comparison. The Eclipse 

Varian TPS, V.8.1, was used for planning. Doses to 16 points distributed 

throughout the superior breast quadrants were calculated and measured by 

thermoluminescent dosimetery (TLDs). The IMRT planning was performed 

for a concomitant boost technique based on our protocol with 57.6, 66, 70.4 

Gy to LRCTV, HRCTV and GTV levels respectively within 32 fractions. The 

half beam block (HBB) AP field and AP/PA fields were calculated for 54 Gy 

at LRCTV levels within 30 fractions for a low and high match line. Optimized 

IMRT plans were generated for each patient with 9 coplanar fields and delivered 

using the 6 MV beam of a Primus Siemens Linac. 

Results: The Eclipse-calculated dose was less than the measured dose for 

the 16 points for all plans. The difference increased with the distance from the 

field. The data show that the mean dose per fraction to the proximal part of the 

superior quadrants of the breast tissue is higher when we combine an AP/PA 

HBB or AP HBB with IMRT versus IMRT only (11cGy vs 8.6 cGy) .The mean 

dose per fraction to the distal part of the superior breast quadrants varies from 

3 cGy to 4.7 cGy with the minimum dose corresponding to AP HBB/ IMRT and 

maximum to AP/PA HBB/ IMRT. The maximum mean proximal (336.75cGy) 

and distal (130.5 cGy) dose for the whole treatment was given by the AP/PA 

HBB/ IMRT plan. The minimum mean proximal dose for the whole treatment 

was given by IMRT only (273.6cGy) and the minimum mean distal dose by 

AP HBB/ IMRT (100.5cGy). 

Conclusions: The combination of AP/PA HBB/ IMRT gives the highest dose 

to the breast during head and neck irradiation .All other techniques deliver 

doses from 20 to 30% less. For young female patients it is critical to choose 

the technique which may decrease most the risk of a dose-related second 

primary malignancy. 

779 poster 

BRACHYTHERAPY AS PART OF A MULTIDISCIPLINARY TREAT- 

MENT FOR CHILDREN WITH RHABDOMYOSARCOMA IN THE 

CLINICAL/DISEASE SITES : HEAD AND NECK 

S 251 

HEAD AND NECK REGION 

C. Koning 1 , L. Blank 2 , K. Koedooder 2 , H. van der Grient 2 , M. van de Kar 

2 , J. Buwalda 3 , H. Merks 4 , S. Strackee 5 , N. Freling 6 

1 

ACADEMIC MEDICAL CENTER AMSTERDAM, Radiotherapy, Amsterdam, 

Netherlands 

2 

ACADEMIC MEDICAL CENTER, Radiotherapy, Amsterdam, Netherlands 

3 

UMCU, ENT, Utrecht, Netherlands 

4 

ACADEMIC MEDICAL CENTER, Department of Paediatric Oncology, 


5 

ACADEMIC MEDICAL CENTER, Department of Plastic and Reconstructive 

Surgery, Amsterdam, Netherlands 

6 

ACADEMIC MEDICAL CENTER, Radiology, Amsterdam, Netherlands 

Purpose: To cure children with rhabdomyosarcoma in the head and neck region 

(the orbit excluded) forms a major challenge for the pediatric oncological 

community. A multidisciplinary approach, consisting of consecutive Ablative 

Surgery, MOuld technique afterloading brachytherapy and immediate surgical 

REconstruction (AMORE), to be applied after chemotherapy according to 

SIOP protocols, was designed. The treatment data are analysed and results 

are presented. 

Materials: After macroscopically radical tumorresection, moulds constructed 

for each individual, were placed fitting into the surgical defect. The moulds 

were made of 5 mm thick layers of thermoplastic rubber, consisting of different 

parts. Flexible catheters were positioned between the layers. By this 

approach wound collapse and displacement of the catheters were avoided. 

Twenty nine patients were treated with LDR; 13 with PDR; both were well tolerated. 

The dose to the CTV, varying between 40 and 50 Gy was given to 

42 patients, treated form 1993 until 2007, divided over the primary treatment 

group (31 patients) and salvage treatment (11 patients). Twenty nine tumors 

were located in the parameningeal (pm) and 13 in the non-parameningeal 

(npm) regions. The age of the patients at the moment of AMORE varied from 

1.2-16.9 years with an average of 6.5 years. Eighteen were females and 24 

were males. Follow-up varied from 0.15 to 14.5 years with an average of 

more than 5.5 years. 

Results: Eleven patients died: three from local recurrence only, six with local 

and distant disease, one due to distant metastases only and one patient from 

a second primary tumor. The overall 5 year survival for the primary treatment 

group is 70 %, for the pm group 66% and for the npm group 83 % respectively. 

For the salvage group the 5 year survival rate is 82 %. The treatment was 

tolerated very well, acute toxicity was mild. Late side-effects were unavoidable 

and were partly related to tumorgrowth, surgery and/or radiotherapy. In 

general they were acceptable. 

Conclusions: The AMORE protocol is feasible; local control and overall survival 

rates are good and side effects are acceptable. 

780 poster 

CHEMORADIATION (CRT) FOR LOCALLY ADVANCED SQUAMOUS 

CARCINOMA OF THE HEAD & NECK (HNSCC) USING CONCUR- 

RENT 3-WEEKLY CISPLATIN CHEMOTHERAPY: COMPLIANCE AND 

ACUTE TOXICITY 

M. Lei 1 , O. Chan 1 , A. Franklin 1 , M. E. A. O’Connell 1 

1 GUY’S AND ST THOMAS’ NHS FOUNDATION TRUST, Clinical Oncology, 


Purpose: Platinum based CRT is the non-surgical standard therapy for locally 

advanced HNSCC. However, dose scheduling remains contraversial. We report 

compliance and toxicity for outpatient 3-weekly Cisplatin chemotherapy 

concurrent with radical radiotherapy. 

Materials: From June 2003 to December 2007, 138 patients with locally 

advanced HNSCC received Cisplatin 75mg/m 2 on days 1,22,40 concurrent 

with radiotherapy 65Gy in 30 daily fractions. Patient details, acute toxicity,recurrence 

and survival data were recorded. 

Results: There were 138 patients: 107 males and 31 females of mean age 

57 years (range 31-83) with biopsy proven HNSCC. Mean follow-up was 413 

days (range 60-133). Tumour sites were oropharynx 78,larynx 35,nasopharynx 

16,paranasal sinus 5, other 4. 39 patients were Stage lll and 99 Stage lV. 

Mean overall treatment time was 43 days (range 40-46). 91% completed CRT 

without gaps. Delays were due to transport failure in 3; patient choice/holiday 

in 7; unexpected death in 2. 113 patients had insertion of a feeding gastrostomy 

tube before CRT and 8 required nasogastric tubes during CRT. 107 

(77%) completed 3 cycles of Cisplatin. 21 (16%) completed 2 cycles owing 

to neutropenia in 7 patients; non-neutropenic sepsis in 4;frailty in 4;Grade 2 

emesis in 2;cardiac arrest in 1;cachexia in 1,tinnitus in 2. 10 (7%) had 1 cycle 

only owing to Grade 3 neutropenia in 1; Grade 2 neutropenia in 4;cachexia in 

1;Grade 3 emesis in 1, frailty in 3. 43 patients required hospital admission for 

a mean of 19 days (range 2-66) with sepsis in 14; cachexia in 12;emesis in 

6; frailty in 11. 59 patients required blood transfusion for Grades l/2 haematological 

toxicity. Overall survival was 80% with disease free survival 70%. 

There were no treatment-related deaths. 

Conclusions: Chemoradiotherapy using concurrent 3-weekly Cisplatin 

75mg/m 2 ia an active well-tolerated outpatient regimen with favourable rates 

of local control and survival.


781 poster 

COMPARISON OF THE CONVENTIONAL 2-D TREATMENT TECH- 

NIQUE WITH 3-D CONFORMAL RADIOTHERAPY IN PATIENTS 

WITH NASOPHARYNGEAL CANCER (NPC) 

P. Gkogkou 1 , C. Armpilia 1 , M. Balafouta 1 , V. Michalaki 2 , C. Antypas 1 , A. 

Zygogianni 1 , K. Gennatas 2 , I. Kouvaris 1 

1 

ARETAIEIO HOSPITAL UNIVERSITY OF ATHENS, Radiation Oncology, 


2 

ARETAIEIO HOSPITAL UNIVERSITY OF ATHENS, Department of Pathology 

Oncology, Athens, Greece 

Purpose: To evaluate the benefit of using 3-dimensional conformal radiotherapy 

(3D-CRT) in cancer patients with nasopharyngeal cancer (NPC) using a 

6MV photon beam. 

Materials: Twenty randomly chosen patients with NPC were retrospectively 

studied. For ten patients a 2-D technique was planned using bilateral opposing 

faciocervical fields and one lower anterior cervical field. PTV1 (Phase 

I) included the macroscopic tumour volume, the nearby anatomic structures 

and the regional bilateral upper neck lymphatics. PTV2 (Phase II) included 

the primary tumour and the retropharyngeal area. Phase II was planned using 

bilateral opposing fields but the spinal cord was shielded. For the other 

ten patients 3-D conformal technique was planned for the entire course of 

treatment (PTV1 and PTV2). The lower neck was irradiated using a matched 

anterior field with a central block. Treatment plans for both techniques were 

assessed based on dose distributions. For 3D-CRT dose volume histograms 

were also considered. The total median prescribed dose was 64Gy. 

Results: Comparison between 2-D RT and 3D-CRT showed that 3D planning 

allows for better delineation of tumour target, for clearer delineation of critical 

normal tissues and for more accurate dosimetry. Thus, with 3D-CRT higher 

doses can be delivered to the tumour volume without increasing the dose to 

normal structures. 

Conclusions: The results suggest possible advantages such as preservation 

of salivary functions, improved local tumour control and patient survival, 

arising from the use of 3D-CRT over the standard conventional 2-D technique 

for the treatment of nasopharyngeal cancer. 

782 poster 

CONVENTIONAL, 3DCRT AND IMRT PLANNINGS AT NECK NEG- 

ATIVE NASOPHARYNGEAL CARCINOMAS: THE DIFFERENCES 

BETWEEN THE DOSES AND VOLUMES OF THE PAROTID AND 

SUBMANDIBULAR GLANDS 

N. Dag 1 , F. Akman 1 , S. Kurt 1 , M. Kinay 1 

1 DOKUZ EYLUL UNIVERSITY, Radiation Oncology, Izmir, Turkey 

Purpose: The aim of this study is to compare the effects of the conventional, 

3DCRT and IMRT treatment plannings over the target volumes and normal 

tissues. 

Materials: The study population consisted of 10 patients with T1-4, N0, M0 

nasopharyngeal carcinoma. All of the patients had their treatment at Dokuz 

Eylul University between June 2002 and December 2004. For this study we 

used the computerized tomography images of the patients which were taken 

in our institute for treatment planning. For each patient GTV, CTV, PTV and 

OAR were contoured according to ICRU 50 and 62. After defining the targets 

and OAR conventional, 3DCRT and IMRT plannings were made. Twoopposed 

isocentric lateral fields and an anterior field were used for conventional 

planning, non-coplanar isocentric 5 fields were used for 3DCRT and 

non-coplanar isocentric 7 fields were used for IMRT planning. At conventional 

and 3DCRT, total dose of 70 Gy with 2 Gy per fraction was planned for 

GTV and total dose of 50 Gy with 2 Gy per fraction was planned for CTV. Simultaneous 

Integrated Boost technique was used for IMRT planning and we 

gave a total dose of 66 Gy at 30 fractions to GTV and total dose of 54 Gy at 

30 fractions to CTV. After choosing the suitable isodose curve, we evaluated 

the DVH’s of each treatment planning. To evaluate the differences between 

the target volumes and normal tissues we calculated the mean dose percentages 

of GTV, CTV and PTV and the V26 Gy (the volume which has ≥26 

Gy) volumes of bilateral parotid glands and D50(the dose of the 50% volume) 

doses of bilateral submandibular glands. We used SPSS version 11.0 to collect 

the data and paired samples t test for evaluating the differences between 

the treatment plannings 

Results: At IMRT the mean dose percentages are higher than 3DCRT for 

GTV and PTV (p=0,003 and p=0,019). For these two target volumes there 

isn’t any significant difference between the conventional treatment planning 

and 3DCRT or IMRT. For CTV the mean dose percentages are higher at 

conventional treatment planning than 3DCRT (p=0,019), at IMRT the dose 

percentages are statistical higher than conventional planning (p=0,001) and 

3DCRT (p

public transport, sheet of information, etc. In the brochure "Information for you 

who receives radiotherapy towards ear- nose and throat area" the patient can 

read the following: * What is radiation therapy? * Preparations before radiation 

therapy * Treatment documentation * Treatment * Verification of the 

treatment * Contact with dentist and dental hygienist * Nutrition * Doctor appointments 

* What to think about during radiation therapy * Side effects: Skin, 

Mucous membranes, Pain, Loss of hair 

Conclusions: The first patient received a diary and an information brochure 

in December of 2007. In the end of February of 2008 we had delivered 22 

examples. The reactions from the patients are so far positive. They are very 

content to have all this information regarding their decease in one place and 

under their own supervision. When the diary and information brochure has 

been used for a year there will be an evaluation. 

785 poster 

DIFFERENCES IN FEEDING TUBE REQUIREMENTS FOR PATIENTS 

TREATED WITH IMRT VERSUS TWO DIMENSIONAL RADIATION 

TECHNIQUES FOR ADVANCED HEAD AND NECK CANCER. 

J. Waldron 1 , A. Bayley 1 , B. Cummings 1 , L. Dawson 1 , J. Kim 1 , J. Ringash 

1 , B. O’Sullivan 1 


Purpose: To describe differences in feeding tube requirements between patients 

with advanced head and neck cancers treated with accelerated hyperfractionated 

radiation using IMRT verses two dimensional (2DRT) techniques. 

Materials: Two cohorts of patients were compared. The first cohort of patients 

(N=107) was part of a prospective dose escalation study of hyperfractionated 

accelerated radiation conducted between 1998 and 2003 utilizing 

2DRT. The second cohort of patients (N=70) were treated with the same fractionation 

scheme between 2005 and 2007 utilizing IMRT. The dose to the 

primary site for both cohorts was 64 Gy delivered in 40 fractions bid over 4 

weeks. The dose delivered to uninvolved at risk neck regions for the 2DRT 

cohort was 48 Gy in 30 fractions bid over the first 3 weeks of treatment. For 

the IMRT cohort this dose was 46 Gy in 40 fractions bid over 4 weeks delivered 

simultaneously with the high dose to the primary site. For IMRT planning 

uninvolved midline structures including mucosa, esophagus and post cricoid 

pharynx were contoured and plans were generated to attempt to limit their 

mean dose to 40Gy and maximum point dose to 45Gy. For both cohorts percutaneous 

feeding tubes were inserted prophylactically at the time of treatment. 

Tubes were removed when swallowing function had recovered enough 

to permit sufficient oral intake. Time between tube insertion and removal 

or last follow-up with the tube still in place was calculated for each patient. 

Kaplan-Meier rates of tube dependence were calculated for each cohort. 

Results: The characteristics of the two cohorts treated with 2DRT vs IMRT 

were as follows: Primary sites (oropharynx 58% vs 50%, larynx 27% vs 36%, 

hypopharynx 15% vs 14%), T Categories (T1 4% vs 3%, T2 14% vs 23%, 

T3 48% vs 54%, T4 34% vs 20%), Node positive 68% vs 56%, median age 

58 (range 35-76) vs 66 (range 43-78), median follow up time 2.6 years vs 1.1 

years. Median duration of tube feeding: 21 weeks vs 16 weeks. Actuarial 

rates of feeding tube dependence for the 2DRT vs IMRT cohorts at 6 months 

and one year post insertion were 47% vs 27% and 24% vs 9% (p=0.002, 

log-rank). 

Conclusions: These results indicate patients treated with IMRT techniques 

had significantly less long term requirements for tube feeding. The reasons 

for this observation are likely multifactorial and in part influenced by differences 

in these sequential nonrandomized cohorts. However, this data suggests 

that by permitting dose to the uninvolved neck to be delivered over 4 

weeks rather than 3 weeks and allowing greater conformality in the high dose 

volume, the need for long term tube use is reduced with IMRT. Conclusions 

as to the efficacy of this approach await further follow up in the IMRT cohort. 

786 poster 

DOES CRANIAL NERVE DEFICIT INDICATE LESS FAVOURABLE 

PROGNOSIS THAN ADVANCED CERVICAL NODAL DISEASE IN 

PATIENTS WITH NASOPHARYNGEAL CARCINOMA? 

R. Meral 1 , S. Tuna 2 , R. Disci 3 , A. Karadeniz 4 , M. Altun 4 

1 IU ONCOLOGY, Radiation Oncology, Istanbul, Turkey 

2 IU ONCOLOGY, Medical Oncology, Istanbul, Turkey 

3 IU ONCOLOGY, Biostatistics and cancer epidemiology, Istanbul, Turkey 

4 IU ISTANBUL MEDICAL FACULTY, Radiation Oncology, Istanbul, Turkey 

Purpose: This study aims to show that the presence of a cranial nerve (CN) 

deficit can be a less favourable prognostic feature than the presence of "advanced 

cervical nodal involvement" (N3) in patients with nasopharyngeal carcinoma 

(NPC). 

Materials: We retrospectively reviewed the clinical findings and radiological 

findings in 250 NPC patients diagnosed consecutively between 1990 and 

1998. Eighty-five patients who were also reviewed in terms of treatment outcome 

were found to have CN deficit or N3 regional disease only. The median 

follow-up of these 85 patients was 36 months (range, 2-200 months). Statistical 

analyses were performed using the chi-square test and the Kaplan-Meier 


S 253 

method. 

Results: At the time of diagnosis, 34 (40%) of the 85 had a CN deficit, and 

51 (60%) had N3 without CN deficit. Disease-free median survival was 7 

months in patients with CN deficit and 34 months in patients with N3 (nearly 

significant, p = 0.054). Overall median survival was 18 months in patients 

with CN deficit and 75 months in patients with N3 (p = 0.013). When the 

two groups were compared after stratification for histopathology (WHO 1 / 

WHO 2-3) and age (>50 / 0.1), though the overall survival difference between 

the two groups for younger patients with WHO 2-3 histopathology was nearly 

significant (p = 0.058). 

Conclusions: The presence of CN deficit and N3 disease in patients with 

NPC were equal in terms of prognosis. However, there was a big overall 

survival difference in favour of N3 disease between the two groups that did 

not reach the level of statistical significance. We suggest further evaluation of 

these two categories of locoregionally advanced NPC with more patients. If 

the less favourable prognosis of the presence of CN deficit compared with N3 

disease can be proved, this will have an impact on the staging and treatment 

of nasopharyngeal carcinoma. 

787 poster 

DOSE-VOLUME PREDICTORS FOR SALIVARY DYSFUNCTION 

AND RECOVERY IN PARTIALLY IRRADIATED PAROTID AND 

SUBMANDIBULAR GLANDS IN HEAD AND NECK CANCERS 

C. Rabuka 1 , A. Thompson 2 , V. Moiseenko 3 , A. Hovan 1 , J. Wu 4 

1 VCC/BCCA, Oral Oncology, Vancouver, Canada 

2 UBC/BCCA, Radiation Oncology, Vancouver, Canada 

3 VCC/BCCA, Medical Physics, Vancouver, Canada 

4 VCC/BCCA, Radiation Oncology, Vancouver, Canada 

Purpose: Xerostomia is a debilitating toxicity in head and neck cancer 

(HNC) patients treated with radiation therapy (RT). Some authors have reported 

a dose-volume relationship for salivary function based on a variety 

of RT techniques. In this study, we correlated objective salivary dysfunction 

and recovery outcomes with three-dimensional conformal (3DCRT) and 

intensity-modulated radiotherapy (IMRT) dose data for both the parotid and 

submandibular glands to produce dose response curves and predictive factors 

for xerostomia. 

Materials: All seventy HNC patients included in this study were CT planned 

(Varian, Eclipse) and treated with either IMRT or 3DCRT using a variety 

of uni- and bilateral techniques. Prescribed doses ranged from 40-70Gy, 

2Gy/fraction, 5 fractions/week. All patients had their stimulated and unstimulated 

whole mouth salivary function measured prior to RT and post-RT at 3 

and 12-24 months. Grade IV xerostomia was defined as ≤25% pre-RT salivary 

output (LENT SOMA scale). The different RT techniques produced variable 

dose-volume histograms (DVHs) for individual parotid and submandibular 

glands. The Lyman-Kutcher-Burman normal tissue complication model 

was used to describe the dose-volume response of unstimulated and stimulated 

SF. Multivariate logistic regression analysis was performed to investigate 

the effect of patient- and treatment-specific parameters such as RT technique, 

chemotherapy, demographics and cancer type. 

Results: A detailed analysis of the 70 patients will be presented, including 

dose-volume predictors for xerostomia, and a comparison of salivary output 

and recovery between RT delivery techniques. An initial analysis of 28 

patients with 3-month resting and stimulated SF revealed 18 (64%) and 17 

(61%) had grade IV xerostomia, respectively. 34 patients with 12-24 month 

resting and stimulated SF revealed 16 (47%) and 13 (38%) had ongoing 

grade IV xerostomia, respectively. Further dosimetric and statistical analyses 

will be performed to provide comparisons between different RT techniques 

and their associated salivary function toxicities. 

Conclusions: Salivary function has a significant impact on a patient’s quality 

of life; techniques to improve SF should be a priority for all HNC patients 

treated with RT. Preliminary results indicate that some degree of SF recovery 

occurs 12-24 months post-RT. Strategies to maximize this recovery will be 

discussed. 

788 poster 

DOSIMETRIC PREDICTORS OF PEG TUBE DEPENDENCY IN 

OROPHARYNGEAL CARCINOMA AFTER EXCLUSIVE IMRT 

G. Gunn 1 , G. Sanguineti 2 , N. Rao 1 , E. Endres 3 , M. Cianchetti 1 , B. 

Parker 4 

1 

UNIVERSITY OF TEXAS MEDICAL BRANCH, Radiation Oncology, Galveston, 

USA 

2 

THE SIDNEY KIMMEL COMPREHENSIVE CANCER CENTER AT JOHNS 

HOPKINS, Department of Radiation Oncology and Molecular Radiation 

Sciences, Baltimore, USA 

3 

UNIVERSITY OF TEXAS MEDICAL BRANCH, Radiation Oncology Physics, 

Galveston, USA 

4 

MARY BIRD PERKINS CANCER CENTER, Medical Physics, Baton Rouge 

LA, USA


Purpose: To explore dosimetric predictors of PEG tube dependency in patients 

with oropharyngeal carcinoma treated with definitive IMRT alone. 

Materials: Patients treated at UTMB for oropharyngeal cancer from 2003 to 

2007 with definitive IMRT alone (no chemotherapy) were selected. For these 

patients, our policy has been to recommend a PEG tube only if/when clinically 

indicated and to leave it in place until unused. The doses to selected organs 

at risk (OAR) were retrospectively collected as cumulative DVHs. OAR considered 

were the superior, middle, and inferior constrictor mm (SC/MC/IC), 

the cricopharyngeus m (CR) and the cervical esophagus (CE). The relative 

volume of each OAR receiving at least 40, 50, 60 and 70 Gy were extracted 

and categorized as dichotomous variables using median values as the cutoff. 

The time to PEG dependency was calculated actuarially with Kaplan Meier 

from the last day of treatment until the date of PEG removal. Patients without 

PEG placement were considered events at time zero. All patients getting 

a PEG tube, except for one patient who died of intercurrent disease at 3 

months, were followed until removal or, if not, for at least 30 months. Groups 

were compared using univariate analysis with log rank test. No multivariate 

analysis was attempted. 

Results: 58 patients were included in the analysis. 37 patients did not need 

a PEG tube. Of those getting a PEG tube, median duration of PEG dependency 

was 3.3 months (range 1.8-32.7 months). PEG dependency correlated 

with: V60 for all 3 constrictors (p=0.009,

792 poster 

FDG-PET/CT SIGNIFICANTLY IMPACTS ON THE MANAGEMENT OF 

HEAD AND NECK CANCER- THE ROYAL MARSDEN EXPERIENCE 

P. Dandekar 1 , Y. Barbachano 2 , G. Cook 3 , P. Rhys-Evans 1 , C. Nutting 1 , 

K. Harrington 1 , K. Newbold 4 

1 

THE ROYAL MARSDEN NHS FOUNDATION TRUST, Head and Neck , Sutton, 


2 

THE ROYAL MARSDEN NHS FOUNDATION TRUST, Clinical Research and 

Development , Sutton, United Kingdom 

3 

THE ROYAL MARSDEN NHS FOUNDATION TRUST, Department of Nuclear 

Medicine PET , Sutton, United Kingdom 

4 

THE ROYAL MARSDEN NHS FOUNDATION TRUST, Department of Head, 

Neck Thyroid Unit , Sutton, United Kingdom 

Purpose: Retrospective analysis of the impact of FDG-PET/CT on the management 

of Head and Neck Cancer (HNC) at a single institution. 

Materials: 157 patients with HNC referred to the Royal Marsden Hospital and 

underwent 201 FDG-PET/CT scans between March 2003 and January 2008. 

Data was collected retrospectively from patient records and scan reports were 

compared to clinical examination and anatomical imaging such as CT and 

MRI. 

Results: The median age 56.9 years and 73% were males. The primary 

site of disease was as follows: 35% oropharynx, 20% oral cavity, 6% larynx, 

4% hypopharynx, 5.5% thyroid and 10% other including salivary gland tumours. 

20% presented with cervical lymph nodes of unknown primary. The 

recorded reason for PET/CT was as follows: 20% for staging, 10% to identify 

primary site, 47% to identify disease recurrence, 10% to assess response 

to chemotherapy or radiotherapy, 9% for routine follow up and 3.5% as a 

part of a research protocol. Pathological correlation for the primary site was 

available in 52/157 patients of which 88.4% confirmed the PET/CT finding. 

42/157 patients had pathological correlation for nodal status of which 92.8% 

confirmed the PET/CT findings. Following conventional diagnostic workup, 

PET/CT changed the status of primary (T) in 27.4%, nodes (N) in 20.9% and 

distant metastasis (M) in 16% of examinations. Management was altered due 

to PET/CT in 23% of the whole population; in 56% of patients who had change 

in T stage on PET/CT (Fisher’s exact test p= 98% of the prescribed dose, 

were 92.5%. The mean fraction of PTV1 receiving >98% of the prescribed 

dose, were 92%. Homolateral parotids from GTV received a mean dose of 

27Gy and the controlateral parotids received a mean dose of 22.4Gy. On 18 

evaluable patients, no G4 toxicity was observed. Acute oral mucositis : G2 

n=3, G3 n=15. Acute skin toxicity : G1 n=2, G2 n=13, G3 n=3. Acute xerostomia 

: G1 n=9, G2 n=8, G3 n=1. 7 patients needed a nutritionnal support 

(2 with nasogastric tube and 5 with gastrostomy), 3 patients interrupted treatment 

(3 to 8 days) for acute toxicity. With a median follow-up of 4 months (3 

weeks-8 months), the locoregional control was 100%. 

Conclusions: Those results confirm the effectiveness of IMRT by helical tomotherapy 

to spare parotid glands without degradation of the target volumes 

coverage, in the treatment of head and neck cancer. Helical tomotherapy allows 

precise IMRT and permitting realization of concurent radiochemotherapy 

or SIB scheme radiotherapy with an acceptable toxicity profile. 

795 poster 

HIGH-RISK HEAD AND NECK CANCERS TREATED WITH POSTOP- 

ERATIVE CONCURRENT RADIOTHERAPY AND CHEMOTHERAPY: 

IMPACT ON OUTCOMES 

S. Benavente 1 , M. Ramos 1 , J. Giralt 1 , A. Urdambidelus 1 , E. Hermosilla 1 

1 VALL DHEBRON UNIVERSITY HOSPITAL, Radiation Oncology, Barcelona, 

Spain 

Purpose: To evaluate the impact of concomitant postoperative radiochemotherapy 

on high-risk head and neck cancer patients in a single institutional 

setting. 

Materials: Between 1999 and 2005, 75 patients with a minimum follow-up of 

2 years were analyzed. 60 to 66 Gy in 6-7 weeks plus concurrent cisplatin 

(100 mg/m2 on days 1, 22 and 43) were administered. 

Results: Distribution of high-risk features was: pT3-4, 47%; pN+, 86%; LVI,


12%; PNI, 13%; margins(+), 39%; and ECE(+), 35%. 5-year LRC, OS and 

CSS were 58%, 46% and 60%, respectively. Covariates affecting OS were 

tumor stage (p=0.006) and margin status (p=0.001). In subset analyses, certain 

benefit in nodal relapse was seen if pN2 or ECE(+) were present while 

patients with margins(+) did very poorly. Metastatic disease ranged from 16% 

to 23%, developing earlier if margins(+) or ECE(+). Exitus from second tumors 

was about 2-fold or higher for pN2 or margins(+) (14-21%) compared 

with ECE(+) patients (8%). 

Conclusions: Head and neck cancers with positive margins have a very 

poor prognosis following postoperative radiochemotherapy. Metastatic disease 

was present in 16-23% of high-risk patients. Exitus from second cancers 

was higher if margins(+) or pN2 cases. 

796 poster 

IMPACT OF FDG-PET FOR RADIOTHERAPY PRESCRIPTION 

TO NECK NODES OF HNSCC : A COMPARISON WITH CT TO 

PATHOLOGY. 

S. Deheneffe 1 , J. Installe 2 , H. Crevecoeur 3 , J. F. Daisne 1 

1 

CLINIQUE & MATERNITÉ STE-ELISABETH, Radiation Oncology, Namur, 

Belgium 

2 

CLINIQUE & MATERNITÉ STE-ELISABETH, Nuclear Medicine, Namur, 

Belgium 

3 

CLINIQUE & MATERNITÉ STE-ELISABETH, Department of Cervico-maxillo- 

facial Surgery, Namur, Belgium 

Purpose: The impact of 18-Fluoro-Deoxy-Glucose Positron Emission Tomography 

(FDG-PET) for the delineation of the primary Gross Tumor Volume of 

Head and Neck Squamous Cell Carcinomas (HNSCC) has been demonstrated. 

The impact of FDG-PET for the prescription of radiotherapy to the 

neck nodes still remains unclear.In our center, FDG-PET is systematically 

used in the presurgical work-up of oral cavity / oropharynx HNSCC.In this 

framework, we retrospectively compared the diagnotic performance of Computed 

Tomography Scanner (CT) and FDG-PET to pathological examination 

of surgically removed neck nodes. 

Materials: Between October 2000 and June 2006, 421 patients with oral 

cavity or oropharyngeal HNSCC were investigated preoperatively with CT 

and FDG-PET. Among these patients, 71 were eligible but complete datasets 

(FDG-PET, CT, and pathology) were available for retrospective review for 

21 of them, representing 28 dissected hemi-necks.Pathological analysis was 

considered as the gold standard. For each hemi-neck, sensitivity, specificity, 

positive predictive value (PPV), negative predictive value (NPV) and accuracy 

were calculated for CT and FDG-PET. For the subset of patients with 

pathologically involved nodes, level-by-level correlation was performed. 

Results: Fifteen of the 28 hemi-necks presented pathologically involved 

nodes. Sensitivity and specificity of CT were 73 and 85% and of FDG-PET 67 

and 85%, respectively. PPV and NPV of CT were 85 and 73%, and of FDG- 

PET were 83 and 69%, respectively. Accuracy was 79% for CT and 75% for 

FDG-PET. Level-by-level correlation for involved hemi-necks revealed that CT 

performed better than FDG-PET with respective sensitivity values of 81 and 

63%, specificity of 97 and 87%, PPV of 93 and 67%, NPV of 93 and 85% and 

accuracy of 93 and 80%. FDG-PET showed lower performance because of 

anatomical discrepancies and inability to visualize necrotic nodes. 

Conclusions: The diagnostic performances of CT and FDG-PET are relatively 

equivalent by hemi-necks.For level-by-level analysis, FDG-PET is 

anatomically less accurate. Whether combined PET-CT could relief this limitation 

remains to be investigated.Compared to FDG-PET, CT remains standard 

for neck nodes radiotherapy prescription. The inability of both modalities 

to detect microscopic foci does not preclude the elective irradiation of selected 

clinically uninvolved node levels. 

797 poster 

IMPORTANCE OF CONTOURING THE CERVICAL SPINE LEVELS IN 

IMRT RADIATION FOR HEAD AND NECK CANCERS:IMPLICATIONS 

FOR RE-IRRADIATION 

B. Parashar 1 , C. Kuo 1 , J. E. Meyer 1 , A. Sabbas 1 , D. Nori 1 

1 WEILL CORNELL MEDICAL CENTER, Radiation Oncology, New York, USA 

Purpose: To evaluate the maximum differential cervical spinal (C-spine) cord 

dose in Intensity Modulated Radiation Therapy (IMRT) plans of patients undergoing 

radiotherapy for treatment of head and neck cancer. 

Materials: The C-spine of ten head and neck cancer patients that were 

planned using IMRT was contoured by the same physician with a separate 

contour for each cervical vertebral body. In addition, the right and left sides 

of each cervical cord level were specified by splitting the cord in the center. 

A dose volume histogram (DVH) and maximum point dose were obtained for 

each contour and compared. 

Results: The cord dose varied significantly between cervical cord levels and 

also between the right and the left sides. Further, the dose to the cord was 

dependent on the location of the primary tumor and/or or the high risk areas. 

Cord levels located in the vicinity of the high dose area had a higher maximum 

dose compared to those that were away from that region, though such 

variation was not consistently seen. 

Conclusions: This report provides information that is critical for planning reirradiation 

treatments. Therefore we would recommend that contouring of the 

C-spine cord for every IMRT plan should include outlining of each cervical 

cord level (using cervical vertebrae) and identification of the right and the left 

sides of the cord on each plan. 

798 poster 

IMRT FOR HEAD AND NECK SQUAMOUS CELL CARCINOMA. THE 

CLCC NANTES-ATLANTIQUE EXPERIENCE 

A. Mervoyer 1 , F. Rolland 2 , G. Delpon 3 , F. Drouet 1 , E. Bompas 4 , A. 

Lisbona 3 , L. Campion 5 , E. Bardet 1 

1 

CENTRE RENÉ GAUDUCHEAU, Radiation Oncology, Saint-Herblain, France 

2 

CENTRE RENÉ GAUDUCHEAU, Medical Oncology, Saint-Herblain, France 

3 

CENTRE RENÉ GAUDUCHEAU, Physics, Saint-Herblain, France 

4 

CENTRE RENÉ GAUDUCHEAU, Department of Medical Oncology, Saint- 

Herblain, France 

5 

CENTRE RENÉ GAUDUCHEAU, Department of Statistics, Saint-Herblain, 

France 

Purpose: To review the CRLCC Nantes-Atlantique experience with intensity 

modulated radiotherapy (IMRT) in the treatment of head and neck squamous 

cell carcinoma. 

Materials: From April 2004 to December 2007, 105 patients with head-andneck 

squamous cell carcinoma were treated with IMRT for curative intent. 

Sites included were nasopharynx 7, oral cavity 10, salivary gland 10, oropharynx 

37, larynx 7, facial sinuses 15, hypopharynx 11, and unknown primary 

8. Acute toxicity and late xerostomia were scored using the RTOG radiation 

morbidity scale. Patients who received postoperative IMRT (16), unilateral irradiation 

(19), helical tomotherapy (22) or stereotactic radiotherapy (16) were 

excluded. We kept 32 patients who received a definitive bilateral head and 

neck IMRT. Median age was 59 (range 40-79). There were 14 oropharynx, 

9 hypopharynx, 5 larynx, 2 oral cavities and 2 nasopharynx. The prescribed 

doses were 70 Gy in 35 fractions (35x2 Gy) on the PTV2 (gross tumor volume 

+ margin) and 56 Gy in 35 fractions (35x 1.6 Gy) on the PTV 1 (sub 

clinical region + margin). Ten patients received induction chemotherapy by

TPF (taxotere/cis-platinium/5-fluorouracil), 15 a concurrent chemotherapy either 

with cis-platinium (9) or cetuximab (6). 

Results: D98% were respectively 48.7 Gy for the PTV1 and 65.7 Gy for the 

PTV2. The mean dose to the parotid glands was 30 Gy with a V30 at 43 

Gy. The median follow-up was 15 months (range 1-40). Acute xerostomia 

G3-4 was 33%. Late xerostomia G3-4 was 6%, 3%, and 0% at, 2, 6 and 12 

months respectively. The one-year estimates of progression free rate, tumoral 

progression free rate, regional progression free rate, and overall survival were 

69%, 82%, 88% and 90%. 

Conclusions: Those results have confirmed the effectiveness of IMRT in 

terms of parotid sparing compared to a conventional radiotherapy with no 

influence on loco-regional control or overall survival. 

799 poster 

IMRT IN HEAD AND NECK CANCER 

A. Pedro Olive 1 , C. Lainez 1 , A. Vila 1 , L. M. Moya 1 , J. C. Julia 1 , N. Artola 

1 , A. Sanchez-Reyes 1 

1 HOSPITAL PLATO, Oncology, Barcelona, Spain 

Purpose: Head and neck cancer is an ideal tumor for the intensity-modulated 

radiotherapy (IMRT) because the organ motion is absent with a good immobilization. 

During the last three years, 21 head and neck cancer patients were 

candidates to IMRT in our center. The main inclusion criteria were difficult 

cancer volume, risk organ proximity, prognosis, age and previous radiotherapy. 

Due to the great cost and the very high complexity of this technique, it 

would be desirable to carry out a study of the advisability of the IMRT. Our 

aim was to review our experience in this technique and report dosimetric 

measures, toxicity and outcome. 

Materials: The a priori candidates to IMRT were: 13 nasopharyngeal cancer 

patients (n: 3 relapses, previously irradiated), a hemangiopericytoma, 

a tonsil cancer, a pineal tumor, an esthesioneuroblastoma and 4 pytuitari 

adenomas. All patients were simulated matching CT and MR images (T2, 

T1+gadolinium), and in 3 cases with a FDG-PET/CT guided. The target volume 

(GTV and CTV) were conformed by the aid of the same radiologist. In 

all cases a 3D conformal radiotherapy (3DCRT) planning was performed and 

compared with the IMRT planning in order to decide the advisability of the 

technique. All pytuitari adenomas, the pineal tumor and 5 nasopharyngeal 

cancers included the 3 relapses were early refused to IMRT because the 

planned volumes and risk organs were correctly irradiated using 3DCRT. Finally 

10 patients underwent IMRT. All planning were calculated using sliding 

windows IMRT technique (ECLIPSE, HELIOS module) and treated in a 2100 

C/D 120 multileaf Varian CLINAC. Prescribed doses were 70 Gy in 8 patients 

and 60 Gy in the hemangiopericytoma and esthesioneuroblastoma patients. 

Constrains values were: optic nerve Dmax, 50 Gy; optic chiasm Dmax, 50 

Gy; parotid gland dose as low as possible (mean dose


802 poster 

INTENSITY MODULATED RADIOTHERAPY (IMRT) IN PATIENTS 

WITH HEAD AND NECK CANCER 

D. Van den Weyngaert 1 , D. Van Gestel 1 , B. Dom 1 , D. Schrijvers 2 , J. B. 

Vermorken 3 

1 

ZNA MIDDELHEIM - UZA, University Radiotherapy Antwerp, Antwerp, 

Belgium 

2 

ZNA MIDDELHEIM, Oncology, Antwerpen, Belgium 

3 

ANTWERP UNIVERSITY HOSPITAL, Oncology, Antwerp, Belgium 

Purpose: The treatment of head and neck cancer has evolved in recent years 

and new radiotherapy techniques have entered clinical practice. IMRT in the 

head and neck region is used to homogenize dose distribution and to spare 

the parotid glands, submandibular and minor salivary glands, larynx and swallowing 

structures. In the Ziekenhuisnetwerk Antwerpen (ZNA)-Middelheim, 

IMRT in patients with head and neck cancer has been used since 2003. In 

this retrospective analysis, the treatment results in relation to toxicity and outcome 

are analysed. 

Materials: Patients with histologically proven localized non-metastatic head 

and neck cancer were included in the analysis. They were treated with inversed 

planned step and shoot IMRT. Depending on the type of surgery the 

prescribed doses varied from 60 Gray (Gy) (2 Gy/fraction(fr)) to 66 Gy (2 

Gy/fr) in the postoperative setting and from 66 Gy (2.2 Gy/fr) to 70 Gy (2 Gy/fr) 

in the others. Radiotherapy was given alone, after induction chemotherapy or 

with concomitant chemotherapy. Acute and late toxicity were evaluated by 

RTOG toxicity scales; treatment outcomes (local control rate (LCR), overall 

survival (OS)) were calculated from the start of radiation. 

Results: Between 11/2003 and 6/2007, 86 patients (59 men; 27 women; 

median age 55, range: 34-82 years) with local-locoregional head and neck 

cancer (71 squamous cell carcinoma, 9 adenocarcinoma, 6 undifferentiated 

carcinoma) at different regions (oral cavity 24; oropharynx 22; nasopharynx 

13; larynx 9; hypopharynx 3; and unspecified location 15) were treated with 

IMRT. Most patients presented with a new diagnosis while 8 had locally recurrent 

disease. In patients with a primary diagnosis, treatment consisted 

of induction chemotherapy followed by IMRT in 4 pts; induction chemotherapy 

followed by chemo-IMRT in 16 pts; surgery followed by IMRT in 23 pts; 

surgery followed by concomitant chemo-IMRT in 7 pts; concomitant chemo- 

IMRT in 10 pts; or IMRT alone in 18 patients. 3 patients stopped during IMRT, 

one due to development of a toxic megacolon and 2 due to patient refusal. 

Acute and late toxicities according to treatment are given in Table 1 In the 

observed period 15 patients died: 10 due to tumour recurrence/progression; 

1 toxic megacolon, 1 postoperative complication after salvage surgery, 2 second 

primaries and 1 due to unknown reason. After 3 years LCR was 87% 

(95% confidence interval 78-93%) and OS 70%. 

Conclusions: IMRT is feasible after surgery, induction chemotherapy and in 

combination with chemotherapy or as single treatment modality in patients 

with head and neck cancer. Acute and late toxicity are acceptable with no 

grade 4 toxicity and 3-year LCR and OS are high. 

803 poster 

INTENSITY MODULATED RADIOTHERAPY (IMRT) IN THE MANAGE- 

MENT OF LOCALLY ADVANCED OROPHARYNGEAL SQUAMOUS 

CELL CARCINOMATA (SCC): A REPORT OF CLINICAL OUTCOMES 

FROM A SINGLE U.K. INSTITUTION 

K. Yip 1 , F. Rahman 1 , V. Caskie 2 , C. Dyson 3 , A. Ford 1 , C. D. Scrase 1 

1 

THE IPSWICH HOSPITAL NHS TRUST, Department of Clinical Oncology, 

Ipswich, United Kingdom 

2 

THE IPSWICH HOSPITAL NHS TRUST, Department of Speech and 

Language Therapy, Ipswich, United Kingdom 

3 

THE IPSWICH HOSPITAL NHS TRUST, Department of Dietetics, Ipswich, 


Purpose: Altered fractionation schedules and chemotherapy especially when 

given concurrently with radiotherapy demonstrate improved tumour control of 

head & neck SCC. Both approaches however intensify acute and possibly late 

toxicities. IMRT facilitates normal tissue sparing and might be expected to improve 

the tolerability of such schedules. Since 2002, accelerated radiotherapy 

schedules delivered by IMRT with selective use of concurrent chemotherapy 

have been the standard of care at this institution. This paper evaluates tumour 

control and toxicity especially in relation to swallowing dysfunction and 

trismus in those patients (pts) with locally advanced oropharyngeal SCC. 

Materials: Prospective data collection and retrospective review of all patientrelated 

data since commencement of the IMRT programme was undertaken. 

Pts were assessed by dieticians, speech & language therapists and specialist 

radiographers before, during and after treatment. The Therapy Outcome 

Measure (TOM) scores were used to assess the degree of dysphagia experienced 

by pts after treatment. Trismus was defined as < 3.5cm mouth opening 

at incisors. 

Results: 25 pts received parotid sparing IMRT between 1/2002 and 11/2007. 

Median age was 54 years. All had stage III or IV tumours. 64% were T1/2, 

32% T3/4 and 4% unclassified. 32% were N0, 8% N1, 56% N2 and 4% 

N3. 68% received post-operative radiotherapy (PORT). 6 had concurrent 

chemotherapy (CT), 1 concurrent cetuximab and 10 RT alone. 32% had primary 

radiotherapy (1 ◦ RT). 6 had concurrent CT, 1 concurrent cetuximab and 

1 RT alone. 65Gy in 30 fractions over 40 days was prescribed in 88% pts. 

54Gy in 36 fractions over 16 days was prescribed to 12% pts who required 

PORT. 28% were admitted due to acute complications from treatment. RTOG 

G3 mucositis was reported in 52%. CT where prescribed was delayed or discontinued 

in 42%. RT was delayed or discontinued (by one fraction) in 12%. 

96% pts received nutritional support via gastrostomy tubes. TOM scores of 

swallowing dysfunction are evaluable in 22 pts.18% have returned to normal 

diet, 41% report some dietary modifications, 18% require oral feeding supplements. 

23% are dependent on the non-oral feeding route to varying degrees. 

Treatment related trismus was recorded in 20% all responding to simple intervention. 

With a mean (median) follow up of 20.7 (15.6) months, 88% pts 

are alive and disease free. 8% pts have died without disease. One pt is alive 

with local recurrence at >1year post treatment. 

Conclusions: Intensified schedules of 1 ◦ RT and PORT with IMRT have 

achieved excellent disease control in this pt population with locally advanced 

oropharyngeal SCC. This compares favourably with historical series. Significant 

but manageable acute toxicities were observed. Most pts at the time of 

analysis have reported an effect on their diet post treatment. The data lends 

support to such treatment approaches but is reliant on good multi-disciplinary 

working and appropriate pt selection. 

804 poster 

INTENSITY MODULATED RADIOTHERAPY (IMRT) IN THE TREAT- 

MENT OF MALIGNANCIES OF THE PARANASAL SINUSES AND 

NASAL CAVITY: CLINICAL EXPERIENCE AT A SINGLE U.K. CENTRE 

C. D. Scrase 1 , K. Yip 1 , F. Rahman 1 , A. Poynter 2 , H. James 2 , S. Smith 2 , 

G. Picken 3 

1 

THE IPSWICH HOSPITAL NHS TRUST, Department of Clinical Oncology, 


2 

THE IPSWICH HOSPITAL NHS TRUST, Department of Radiotherapy 

Physics, Ipswich, United Kingdom 

3 

THE IPSWICH HOSPITAL NHS TRUST, Department of Diagnostic Imaging, 


Purpose: Paranasal sinus & nasal cavity tumours present a radiotherapeutic 

challenge because of the close proximity of planning target volume (PTV) to 

normal tissues. Since 2002, IMRT has been the standard of care in the management 

of this group of patients (pts) at this institution. This paper considers 

the tumour type and overall treatment approach, evaluates the dosimetric issues 

and the clinical outcome in this treated population. 

Materials: Prospective data collection and retrospective review of all ptrelated 

data. The IMRT approach was to optimise conformality and dose 

delivery to the PTV whilst keeping the dose to organs at risk (OAR) to within 

conventional tolerance levels unless sparing of the ipsilateral optic nerve compromised 

PTV coverage. 

Results: 21 pts were treated between 3/2002 and 6/2007. 57% received 

post-operative IMRT, 5% post-operative chemo-IMRT, 24% 1 ◦ chemo-IMRT 

and 14% 1 ◦ IMRT alone. 29% were squamous cell carcinoma, 24% olfactory 

neuroblastoma, 14% melanoma, 14% adenocarcinoma, 10% adenoid cystic 

carcinoma, 10% lymphoma or plasmacytoma. 18 pts were stage 3 or 4. All 

patients were treated by a 7 field co-planar arrangement. Mean 1 ◦ PTV was 

297 cm3 (range 84-819.8 cm3) & included one maxillary sinus (n=15) or both 

(n=3) or none (n=3). Median prescribed dose was 60 Gy (range 30-65 Gy 

with daily fractionation over no more than six weeks). The lower doses relate 

to the two haematological tumours. Excluding these, maximum OAR dose 

with 2.5-5mm planning margins (excluding brain) were: optic chiasm 54.7Gy 

(median=46.8Gy); brain stem 51.1Gy (median=24.9Gy); brain 64.3Gy (median=10.4Gy); 

ipsilateral lens 17.6Gy (median=12.1Gy); contra-lateral lens 

18.3Gy (median=11.1Gy); ipsilateral optic nerve 58.7Gy (median=53.9Gy); 

contra-lateral optic nerve 56.0Gy (median=50.3Gy). Acute RTOG G1-2 conjunctivitis 

was reported in 71% with the posterior orbit included within the PTV 

in 20%. In all but one patient this resolved within weeks of treatment completion. 

Nausea was reported by 48% pts. Alopecia occurred in all patients, 

the pattern dictated by the PTV. Late complications are inferior peri-orbital 

lymphoedema that has resolved by 6 months (n=1), RTOG grade 1 bilateral

cataract (n=1) and ipselateral RTOG grade 3 hearing loss (n=1). No other 

significant late effects have emerged thus far. None have reported symptomatic 

dry eyes. With a median follow up of 13.8 months, six patients (27%) 

have died of disease (local or metastatic) and one patient is alive with disease 

recurrence. 

Conclusions: Encouraging disease control has been achieved in some very 

advanced cancers of the paranasal/nasal cavity territory using IMRT. Acute 

toxicities can be anticipated for such of volumes of irradiation. Longer follow 

up is required to allow for a fuller evaluation of the potential late toxicity associated 

with its use. The programme continues with an evaluation of field 

optimisation. 

805 poster 

INTENSITY MODULATED RADIOTHERAPY FOR NASOPHARYN- 

GEAL CARCINOMA; INITIAL EXPERIENCE OF YONSEI CANCER 

CENTER 

C. G. Lee 1 , J. W. Kim 1 , W. S. Koom 1 , Y. B. Kim 1 , I. J. Lee 1 , J. H. Cho 1 , 

K. C. Keum 1 , J. Seong 1 , C. O. Suh 1 , G. E. Kim 1 

1 YONSEI UNIVERSITY MEDICAL COLLEGE, Radiation Oncology, Seoul, 


Purpose: Since May 2002, nasopharyngeal cancer (NPC) patients have 

been treated with intensity modulated radiotherapy (IMRT) at Yonsei Cancer 

Center. We retrospectively analyzed the clinical outcomes of IMRT with 

simultaneously integrated boost technique. 

Materials: Between May 2002 and December 2005, 35 patients with stages 

I to IVB NPC underwent IMRT encompassing 3 targets: gross tumor volume 

(GTV), high-risk subclinical disease (CTV1), and low-risk subclinical disease 

(CTV2). Daily fractions of 2.12, 1.8 and 1.7 Gy were delivered to GTV, CTV1 

and CTV2 to total doses of 70.0, 59.4 and 56.1 Gy in 33 fractions over 7 

weeks, respectively. Twenty patients (57%) received concurrent chemotherapy; 

weekly cisplatin (DDP group, 7 patients), 5FU-Cisplatin-Taxotere (FTP 

group, 12 patients), and 5FU-Carboplatin (1 patient) 

Results: With a median follow-up of 33 months, there were 2 local recurrences 

in GTV, 2 regional recurrences in CTV1, and 6 distant metastases. 

Three year overall and local-, regional-, and distant-metastasis free survivals 

were 88.3% and 94.0%, 93.2%, and 85.5%, respectively. Grade 3 acute mucositis 

was observed in 10 (29%) patients 8 (23%) patients in the CCRT group 

vs. 2 (6%) patients in the RT alone group (p=0.14), and 8 (23%) patients in 

the FTP group vs. none in the DDP group (p = 0.01). At 9 month-follow-up, 

Grade 2 xerostomia was observed in 17 (49%) patients 13 patients in the 

CCRT group vs. 4 patients in the RT alone group (p=0.03). No patient experienced 

xerostomia of Grade 3 or higher. Mean dose to total parotid volume 

(Dmean_TP) and Dose to 50% parotid volume (D50_TP) showed no significant 

correlation with prevalence of xerostomia at 9 month-follow-up (p=0.16 

and p=0.09, respectively). 

Conclusions: Initial IMRT experiences of our institution for nasopharyngeal 

cancer were encouraging, and the dose fractionation scheme proved feasible 

without serious complications. 

806 poster 

INTENSITY MODULATED RADIOTHERAPY FOR PRIMARY IN- 

TRAOCULAR LYMPHOMA: EARLY TREATMENT OUTCOMES IN A 

SERIES OF 5 PATIENTS 

E. Nowakowska 1 , P. Martenka 1 , D. Jezierska 1 , K. Adamska 1 

1 WCO, Radiotherapy, Poznan, Poland 

Purpose: To assess the clinical outcome and ocular complications of a cohort 

of patients with primary intraocular lymphoma (PIOL) treated with intensity 

modulated radiotherapy (IMRT). 

Materials: Retrospective case analysis of medical records of a series of 

consecutive patients presenting with PIOL in Wielkopolskie Cancer Center 

treated with IMRT was performed. A total of 5 patients were included. The 

median age of onset of symptoms was 77 years. Most were female (60%) 

and none had bilateral eye involvement .Four patients had low-grade B-cell 

lymphoma and 1 had diffuse large B- cell lymphoma. All patients had clinical 

stage I according to Ann Arbor lymphoma classification and none had general 

symptoms of disease. All patients received intensity modulated radiation 

therapy with total dose range to PTV of 36 - 40Gy and 1,8Gy or 2,0Gy per 

fraction, respectively. 

Results: During time course of radiotherapy only mild toxicity was observed 

which consisted mainly of conjunctivitis of irradiated eye which resolved within 

1 month after completion of radiotherapy. In all patients at the end of radiotherapy 

significant clinical improvement was observed in terms of pain of the 

eye, ocular swelling, and exophthalmus. Clinical improvement was sustained 

at control visits at 3 and 6 months after completion of radiotherapy. At 6 

months after radiotherapy radiological complete remission in magnetic resonance 

imaging was observed in 1 patient and partial remission in remaining 

4 patients 

Conclusions: Intensity modulated radiotherapy for primary intraocular lymphoma 

in an elderly population seems to be very effective in terms of clinical 


as well as radiological response and is associated with low toxicity. 

807 poster 

S 259 

INVOLVED FIELD IRRADIATION IN HEAD AND NECK LOCALIZED 

DIFFUSE LARGE B-CELL LYMPHOMA 

J. Yu 1 , A. Yong Chan 1 , P. Won 1 , K. Won Ki 2 , P. Keun Chil 2 , L. Jeong Ae 

1 

1 

SAMSUNG MEDICAL CENTER, Radiation Oncology, Seoul, Korea Republic 

of 

2 

SAMSUNG MEDICAL CENTER, Department of Internal Medicine, Seoul, 


Purpose: To report the treatment outcomes after combined modality therapy 

(CMT) in patients with stage I/II head and neck (HN) diffuse large B-cell 

lymphoma (DLBL). 

Materials: A retrospective review was performed on 86 patients with stage 

I/II DLBL of HN who received CMT from 1995 till 2006 at Samsung Medical 

Center. The most common involved sites were oropharynx (40.7%) and cervical 

lymph node (38.4%). Involved field radiation therapy (IFRT) was given 

following median 4 cycles of CHOP or R-CHOP chemotherapy. The RT target 

volume was individually determined to cover the known gross lesion with 

adequate margin (2-3cm), and the median radiation dose was 39.8 Gy over 

4-5weeks. 

Results: Overall survival rate (OS) and relapse-free survival rate (RFS) at 

10 years were 74.0 %, and 88.9%. After median follow-up of 57 months (11- 

131), eight treatment failures were observed: distant metastasis in eight; and 

loco-regional failure in four patients. Among four patients with loco-regional 

failure, three presented with in-field failures, and one did with out-field failure 

at contralateral recurrence. During and after completion of RT, there was no 

severe side effect except one patient with grade 3 mucositis. Multivariate 

analyses showed that B symptom (p=0.022) and abnormal LDH (p=0.017) 

were related with poor OS, age older than 60 (p=0.033) was with RFS, and 

International prognostic index (IPI, p=0.03) was related with OS and RFS. 

Conclusions: The results of this study demonstrated that stage I, II head and 

neck DLBCL patients did not need ipsilateral whole neck irradiation. Reasonable 

margin from tumor may reduce radiation toxicity with same treatment 

results. 

808 poster 

IS IT POSSIBLE TO COMPENSATE MICROSCOPIC POSITIVE 

MARGINS OF RECURRENT HEAD AND NECK CANCER WITH 

INTERSTITIAL HIGH DOSE RATE BRACHYTHERAPY COMBINED 

OR NOT WITH EXTERNAL BEAM RADIOTHERAPY? 

A. Pellizzon 1 , P. E. Novaes 1 , J. V. Salvajoli 1 , R. Fogaroli 1 , M. Conte 1 

1 HOSPITAL AC CAMARGO, Radiation Oncology, Sao Paulo, Brazil 

Purpose: It is a controversy issue what is the best approach for isolated 

cervical recurrences of head and neck cancer (rHNC), although surgery is 

mandatory when feasible. A treatment policy combining salvage surgery and 

interstitial high dose rate brachytherapy (I-HDR) was implemented as an institutional 

policy of treatment at the Brachytherapy Service - Hospital AC Camargo, 

besides the paucity of data in the literature. 

Materials: We evaluated the results in terms of local control and survival of 

21 consecutive with rHNC who were submitted to salvage surgery and I-HDR. 

Results: The crude local control rate for all patients was 52.4%. Fifteen 

(71%) patients had had a previous course of external beam radiotherapy 

(EBRT) with a median dose of 45 Gy (range 30-66). The median dose of 

the second EBRT course was 30 Gy (range 25-50). The 10-year overall (OS) 

and local relapse-free survival (LRFS) rates were 42.5% and 27%, respectively. 

The only predictive factor associated to LFRS and OS was negative 

margin status (p = 0.0007 and p = 0.0002). 

Conclusions: The complete surgery is mandatory for local control, but strategies 

involving the use of I-HDR, EBRT and probably concurrent chemotherapy 

shall be necessary to compensate for positive surgical margins. 

809 poster 

IS REPLANNING REQUIRED FOLLOWING SHRINKAGE OF NOR- 

MAL TISSUES IN POST OPERATIVE HEAD & NECK CANCER 

PATIENTS ON IMRT? 

V. Bansal 1 , K. Jani 1 , A. Kumar 1 , D. Bhavsar 1 , V. Subramanian 1 , R. Patel 

2 

1 APOLLO HOSPITALS - CBCC, Radiation Oncology, Gandhinagar, India 

2 CBCC - USA, Medical Oncology, Bakersfield, USA 

Purpose: One of the major objectives of IMRT is to save the parotids in head 

& neck carcinomas. Volumetric changes do occur in head & neck normal 

tissues during the course of radiotherapy. Our aims of the study were (1) 

to evaluate the difference between planned dose & delivered dose to major


critical structures during the course of radiotherapy and (2) to find out optimal 

replanning strategy. 

Materials: In our study we included 7 H & N cancer patients ’operated’ for 

Carcinoma of Buccal Mucosa, Retromolar Trigone & Lower Alveolus. All patients 

were planned by IMRT using 7 or 9 beams for a dose of 60 to 63 Gy to 

be delivered over 30 35 #. All these patients underwent weekly Cone Beam 

CT (CBCT) for isocentric verification, correction of setup errors if any and for 

assessing any gross volumetric change in body contour. Daily orthogonal KV 

beams were used to check and correct any set up errors using Varian’s on 

board imaging device. Using the same immobilization mask weekly planning 

CT scan was done from 5th week onwards (earlier if any gross change in 

body contour seen before 5th week on CBCT). Contralateral parotid & spinal 

cord were contoured on the new CT images and any volumetric change in 

parotid was noted. The original plan was applied to the new scans & doses 

were recomputed for normal structures. Replanning was done weekly keeping 

the same constraints and margins. All weekly cumulative doses to parotid 

and spinal cord were added to arrive at the final doses received by them at 

the end of treatment. 

Results: Contralateral mean parotid dose increased by 12 %, whereas its 

volume reduced by 15 % by the last week of treatment. Volume reduction & 

dropping of parotid to high dose region due to body contour shrinkage seems 

to be the obvious reason for the increase in mean parotid dose. Dmax of 

spinal cord increased in the range of 1.2 8 %. 

Conclusions: Increase in dose to parotid and spinal cord mandates replanning. 

We have re-planned from 5th week onwards due to practical reasons. 

We feel that more frequent replanning and faster planning is the future ahead 

towards realisation of better function preservation. Better & faster algorithms 

to recalculate & sum up the doses and volume changes of critical structures 

over weeks will give realistic dose received to these structures. 

810 poster 

KI-67 PREDICTS LOCOREGIONAL RECURRENCE IN EARLY 

STAGES OF ORAL TONGUE SQUAMOUS CELL CARCINOMA 

D. Wangsa 1 , M. Ryott 2 , J. Luo 3 , G. Elmberger 1 , F. Petersson 1 , G. Auer 

1 , E. Åvall-Lundqvist 4 , E. Munck-Wikland 2 

1 

KAROLINSKA INSTITUTET, KAROLINSKA UNIVERSITY HOSPITAL, Oncology- 

Pathology, Stockholm, Sweden 

2 

KAROLINSKA INSTITUTET, KAROLINSKA UNIVERSITY HOSPITAL, Oto- 

Rhino-Laryngology, Stockholm, Sweden 

3 

KAROLINSKA INSTITUTET, Department of Medical Epidemiology and 

Biostatistics, Stockholm, Sweden 

4 

KAROLINSKA INSTITUTET, KAROLINSKA UNIVERSITY HOSPITAL, Gynaecologic 


Purpose: To investigate the correlation between Ki-67 expression and recurrence 

predictions in OTSCC patients. Our secondary objective was to 

examine the change in Ki-67 expression before and after radiotherapy. 

Materials: Formalin fixed, paraffin embedded biopsy specimens were obtained 

from 76 patients with histopathologically confirmed OTSCC, UICC 

Stages I-IV, treated at the Department of Oto-Rhino-Laryngology, Karolinska 

University Hospital (Stockholm, Sweden) from January 2000 to December 

2004. Immunohistochemical staining with the commercially available monoclonal 

antibody (clone MIB-1 by Dako), was made on 4µm sections using the 

Benchmark XT system, a product of Ventana Medical Systems. This system 

automatically standardizes, prepares and stains the 4µm Ki-67 slide sections 

at the same time. The stained Ki-67 slides were analyzed according to their 

nuclear staining pattern using the VIAS workstation, a Ventana Image Analysis 

System at 400x magnification. Approximately 1000 cells were evaluated, 

with the given percentages from 0 to 100, with 0 being no nuclear staining to 

100 being total nuclear staining of the cells. 

Results: In OTSCC, 50% of the patients died following a minimum follow-up 

time of 3 years, with a median survival time of 22 months. Comparisons revealed 

a significant correlation between a high proliferation rate and tumor 

recurrence in OTSCC patients within Stage 1 (P=0.028). When patients who 

received surgery was combined with those who received pre-operative radiotherapy, 

the correlation between recurrence and a high proliferation rate 

decreased (P=0.047). Ki-67 post-radiotherapy specimens exhibited lower 

proliferation expressions (P=0.001) in all patients who received 50-68Gy preoperative 

radiotherapy. The degree of Ki-67 expression decrease differed 

among the patients, but all patients who developed a cancer recurrence had 

a decrease in Ki-67 expression of 14 or less. 

Conclusions: High proliferation seems to be related to an elevated recurrence 

risk after surgery alone. However, this relation could not be found in 

patients treated with a multi-modality treatment of neoadjuvant radiotherapy 

and surgery. Ki-67 may therefore be a prognostic marker of recurrence in 

OTSCC patients who receive no additional treatment other than surgery. 

811 poster 

LOCALLY ADVANCED LARYNGEAL CARCINOMA (LALC) IN 

PATIENTS WITH SEVERE COMORBILITY: OUTCOME WITH HIPER- 

FRACTIONATED RADIOTHERAPY (HFX) AND CISPLATIN 

G. Asin 1 , R. Lopez 2 , P. Romero 1 , M. Goñi 1 , T. Vila 1 , M. Uzcanga 2 , E. 

Oria 3 , V. Arrazubi 4 , M. A. Domínguez 1 , F. Arias 1 

1 HOSPITAL DE NAVARRA, Radiation Oncology, Pamplona, Spain 

2 HOSPITAL VIRGEN DEL CAMINO, ORL, Pamplona, Spain 

3 HOSPITAL DE NAVARRA, Department of Nutrition, Pamplona, Spain 

4 HOSPITAL DE NAVARRA, Medical Oncology, Pamplona, Spain 

Purpose: To review the outcome of the patients with LALC and bad prognosis 

due to very advanced tumours or severe comorbility treated with HFX and 

concomitant cisplatin. 

Materials: From May/2002, 27 pts with IK>60%, fulfilled the selected criteria 

(at least two of the factors: unresectable tumours, severe cardiovascular 

disease, heavy active smokers (>30 cig/d) and alcoholic drinkers (>200 

mg/d etanol), or chronic hepatopathy (cirrhosis or hepatitis C). There were 

27 pts, 24 stage IV (89%) and 3 III AJCC. Supraglottic and hypopharynx location 

in 22 (82%). Treatment plan: Hyperfractionation (HFX) at 1.2 Gy/fx, 

B.I.D, 5days/week to a total dose of 76.8 Gy to 81.6 Gy., and cisplatin, 20 

mg/m2/day, 5 days, in continuous perfusion, on weeks 1 and 5 of radiation. 

Results: Tumor response (RECIST): complete response: 20 p( 74%), partial 

response: 5p,and 2 NR. Survival: Median follow-up: 21 months (9-52).Two 

years overall survival and Local control 60% and 62%, respectively. Acute 

toxicity (CTCv3.0) Grade III-IV in 15p (56%), most mucositis and epithelitis. 3 

p. (12%) had pneumonia; 4 p. needed tracheotomy by glottis edema. Media 

of hospitalization days due to toxicity: 7 days (0-52). There were no toxic 

deaths. During follow-up, 3 p. had non-tumor related death. 

Conclusions: Including in this bad group of laryngeal cancer, HFX and cisplatin 

can achieve acceptable rate of local control and survival. 

812 poster 

LONG-TERM FOLLOW UP RESULTS OF MALIGNANT MINOR 

SALIVARY GLAND TUMOURS (MSGT) TREATED WITH COMBINED 

SURGERY AND POST-OPERATIVE RADIOTHERAPY (PORT) AT A 

SINGLE CENTRE 

M. E. A. O’Connell 1 , A. Franklin 1 , M. Gleeson 2 

1 

GUY’S AND ST THOMAS’ NHS FOUNDATION TRUST, Clinical Oncology, 


2 


Otorhinolaryngology Skull Base Surgery, London, United Kingdom 

Purpose: Malignant tumours of the minor salvary glands are rare. Initial 

therapy comprises surgery and PORT. We describe long-term results from a 

single centre. 

Materials: A retrospective review of 82 patients with malignant tumours of minor 

salivary gland origin treated between 1975 and 2006 is reported. There 

were 41 males and 41 females of mean age 52 years (range 13-89). Mean 

follow-up was 82 months (range 12-396). Histologically, 34 were adenoid 

cystic (ADC),18 adenocarcinoma (AC),21 mucoepidermoid (MEC),5 acinic 

cell (ACC),2 malignant melanoma and 2 sarcoma. Tumour sites were: palate 

20, maxilla 13, tongue base 8,floor of mouth 6,external auditory meatus 5, 

lip 5,cheek 5,nasopharynx 5,nasal cavity 4, larynx 4,sphenoid sinus 3,retromolar 

trigone 3 and trachea 1. Overall stage groups l-lV were: 13%,41%,5% 

and 40% respectively. Indications for PORT were high grade tumour; microscopically 

involved margins; resection for recurrent disease; invasion of 

skin,bone,nerve; positive lymph nodes; gross residual or unresectable disease. 

PORT doses to the primary and neck if involved were 50-54Gy in 20 

fractions or 60-65Gy in 30 fractions. The clinically negative neck was treated 

to 50Gy in 25 fractions equivalent except for low grade (LG) tumours. 

Results: As a working model tumours were grouped into 2 major categories: 

(i) low grade (LG) consisting of low grade MEC, ACC and low grade AC and 

(ii) high grade (HG) consisting of ACC, high grade AC, high grade MEC, 

melanoma and sarcoma. For LG tumours, 85% were early stages l/ll with 

15% advanced stages lll/lV. In contrast for HG tumours 35% were stages l/ll 

with 65% stages lll/lV. The 5, 10 and 20 year overall survivals were 98%, 

85%, and 80% respectively for LG contrasted with 60%,55% and 45% for 

HG (p=0.005). Cox regression analysis showed lymph node status, nerve involvement, 

vascular invasion and grade to be independent risk factors. Lymph 

node metastases occurred in only 6% and distant metastases (lung and bone) 

in 10% of HG tumours. 

Conclusions: Favourable local control rates and overall survival are achieved 

with combined surgery and radiotherapy. 

813 poster 

LONG-TERM RESULTS OF ORGAN PRESERVATION CHEMORA- 

DIOTHERAPY (CRT) FOR SQUAMOUS CELL CARCINOMA OF THE 

LARYNX (LSCC) TREATED AT A SINGLE CENTRE 

A. Franklin 1 , M. E. A. O’Connell 1 

1 GUY’S AND ST THOMAS’ NHS FOUNDATION TRUST, Clinical Oncology, 

London, United Kingdom

Purpose: Squamous cell carcinoma of the larynx (LSCC) is the most common 

non-cutaneous malignancy of the head and neck. Optimal management 

remains contraversial with a major impact on natural speech and survival. 

We report the long-term results of organ preservation strategies from a single 

centre. 

Materials: Between 1976 and 2007, 272 patients with biopsy-proven LSCC 

were treated using an organ preservation startegy. Patients with early stages 

T1 and T2 tumours were treated with radical radiotherapy 54Gy in 20 fractions. 

Patients with T3N0M0 tumours received radiotherapy 65Gy with concomitant 

3-weekly Cisplatin chemotherapy 75mg/m 2 . Patients with T3 tumours 

and positive lymph nodes and all patients with T4 tumours underwent 

total laryngectomy, neck dissection and post-operative radiotherapy 60-65Gy 

(PORT). Mean follow-up was 36 months (range 6-360).Patient characteristics, 

details of CRT with recurrence and survival data were recorded. 

Results: There were 272 patients: 225 male and 47 female (ratio 5:1) of 

mean age 63 years (range 31-83). The T stages were: Tis and T1 =88(32%), 

T2=98 (36%), T3=50 (18%) and T4=36 (13%). Overall survivals (OS) at 5 

years were: 90%, 85%, 55% and 65% for T1, T2, T3 and T4 respectively 

(Kaplan Meier). OS at 15 years were 70%, 70%, 50% and 35% for T1, T2, 

T3 and T4 respectively. For early T1 and T2 tumours there were 11/186 (6%) 

local failures at 30 years salvaged by laryngectomy. Disappointingly, T3N0M0 

tumours treated with CRT only fared worse than those treated with combined 

surgery and PORT with 2- and 5-year OS 75% and 20% only contrasted with 

85% and 60% respectively. For T4 tumours 6/36 (17%) developed distant 

metastases mainly to the lung. 

Conclusions: Laryngeal function preservation with CRT has gained increasing 

weight. However, this and other published studies have shown inferior survival 

for T3 tumours compared with combined surgery and PORT. This may be 

attributable to neck failure and staged neck dissection should be considered 

even in the clinically negative neck. For T4 tumours induction chemotherapy 

and post-operative CRT should be considered to prevent and/or delay distant 

dissemination. 

814 poster 

MALIGNANT TUMORS OF THE NASAL CAVITY AND PARANASAL 

SINUSES: LONG-TERM OUTCOME AND MORBIDITY WITH EMPHA- 

SIS ON HYPOTHALAMIC-PITUITARY DAMAGE 

A. Snyers 1 , G. Janssens 1 , A. Hermus 2 , M. Twickler 2 , R. Takes 3 , A. 

Kappelle 4 , T. Merkx 5 , P. Dirix 6 , H. Kaanders 1 

1 

UMC ST RADBOUD, Radiation Oncology, Nijmegen, Netherlands 

2 

UMC ST RADBOUD, Department of Endocrinology, Nijmegen, Netherlands 

3 

UMC ST RADBOUD, Department of Otorhinolaryngology - Head and Neck 

Surgery, Nijmegen, Netherlands 

4 

UMC ST RADBOUD, Department of Neurology, Nijmegen, Netherlands 

5 

UMC ST RADBOUD, Department of Oral and Maxillofacial Surgery, 


6 

LEUVENS KANKER INSTITUUT, Radiation Oncology, Leuven, Belgium 

Purpose: To evaluate the long-term outcome after surgery and radiotherapy 

for sinonasal cancer and to assess the late effects of radiotherapy with special 

emphasis on hypothalamic-pituitary dysfunction. 

Materials: A retrospective analysis was performed of 168 patients treated 

for sinonasal cancer at the Radboud University Nijmegen Medical Centre between 

1986 and 2006. A subgroup analysis was done on 76 patients with 

adenocarcinoma or squamous cell carcinomas treated with curative intent. 

Long-term survivors were evaluated for late toxicity by a multidisciplinary 

team of medical specialists using the LENT SOMA scale. Endocrinological 

tests were performed and, when indicated, additional stimulation tests, for 

assessment of hypothalamic-pituitary function. 

Results: Five-year actuarial local control and overall survival rates were 62% 

and 35% for all patients and 64% and 42% for the subgroup with squamous 

cell carcinoma and adenocarcinoma. In the multivariate analysis, T-stage was 

the only significant factor predicting for local relapse (79% at 5-years for T1-3 

vs. 53% for T4, p = 0.006). Sinonasal mucosal melanomas had the highest 

rate of regional failure (33% at 5 years). Grade III-IV late ophtalmic complications 

occurred in 7% but only in 2.4% of cases treated with 3-D conformal 

radiotherapy. Five out of 21 patients (24%) evaluated at the late morbidity 

clinic had hypopituitarism with multiple hormonal deficiencies. 

Conclusions: Local failure is the dominant cause of treatment failure for patients 

with sinonasal cancer with T4-stage being the only independent predictor. 

Because of a high rate of radiation-induced endocrinopathy, we recommend 

endocrinological surveillance for these patients. 

815 poster 

MONITORING DOSIMETRIC IMPACT OF WEIGHT LOSS WITH 

KILO-VOLTAGE (KV) CONE BEAM CT (CBCT) DURING PAROTID 


S 261 

SPARING IMRT AND CONCURRENT CHEMOTHERAPY 

K. Ho 1 , T. Marchant 2 , C. Moore 2 , G. Webster 2 , C. Rowbottom 2 , L. Lee 

3 , B. Yap 3 , A. Sykes 3 , N. Slevin 3 

1 UNIVERSITY OF MANCHESTER, Academic Department of Radiation 


2 CHRISTIE HOSPITAL NHS FOUNDATION TRUST, North Western Medical 

Physics, Manchester, United Kingdom 

3 CHRISTIE HOSPITAL NHS FOUNDATION TRUST, Department of Clinical 


Purpose: Parotid sparing IMRT is increasingly used to reduce long term xerostomia. 

However, head and neck cancer patients receiving radiotherapy frequently 

experience significant weight loss and tumour shrinkage during treatment 

especially when concurrent chemotherapy is used. We aim to examine 

the dosimetric impact of such changes on the parotid and critical structures 

to identify if re-planning of IMRT is required during treatment. 

Materials: Eight patients with non-metastatic stage IV oropharyngeal cancer 

(6 tonsil, 2 base of tongue) were treated with contralateral parotid sparing 

IMRT. Mean doses of 65Gy and 54Gy were delivered to CTV1 and CTV2 

respectively in 30 daily fractions over 6 weeks. Each patient received 2 cycles 

of concurrent platinum based chemotherapy. KV CBCT was prospectively 

acquired at the end of each week. Each CBCT was co-registered with 

planned isocentre. Spinal cord and brainstem were copied onto the CBCT 

and adjusted for spinal curvature movement. Parotids were contoured bilaterally 

on CBCT by a single observer. Dose calculation using original IMRT 

plans was performed on acquired CBCT after correcting grey scale to provide 

Hounsfield unit information. 

Results: End of treatment mean weight loss was 7.5kg (8.8%) of baseline 

weight. Ipsilateral and contralateral parotid showed a mean reduction in volume 

of 29.7% and 28.4% respectively. Planned contralateral parotid mean 

dose, V24, D50 were not significantly different compared to delivered mean 

dose, V24 and D50 during treatment (p>0.1). An increase in delivered mean 

maximum spinal cord dose of 4.4Gy was observed in 1 patient although the 

mean highest dose to 1cc was only 43.9Gy. For the entire patient cohort there 

was no significant difference between planned and delivered maximum dose 

to the brainstem (p=0.6) and spinal cord (p=0.2). Despite a >10% weight 

loss in 5 patients, there was no significant dosimetric change affecting the 

contralateral parotid and neural structures. 

Conclusions: Although patient weight loss and parotid volume shrinkage 

was observed, it was reassuring that overall there was no significant excessive 

dose to the spinal cord, brainstem and contralateral parotid. No replanning 

was felt necessary for this patient cohort but a larger patient sample 

will be investigated to further confirm these results. Weekly KV CBCT is a 

valuable tool for patient setup verification and monitoring of dosimetric variation 

during radiotherapy. 

816 poster 

NASOPHARYNGEAL CANCER BOOSTED BY BRACHYTHERAPY 

OR STEREOTACTIC RADIATION: OBJECTIVE MEASUREMENTS OF 

FUNCTIONAL IMPAIRMENT AND QUALITY OF LIFE ASPECTS 

P. Levendag 1 , C. de Pan 1 , D. Teguh 1 , I. Noever 1 , P. van Rooij 1 , J. 

Feenstra 2 , N. Homans 2 , E. Kilic 3 , M. Hoogeman 1 , P. Schmitz 4 , P. Nowak 

1 

1 

ERASMUS MEDICAL CENTER, Radiation-Oncology, Rotterdam, Netherlands 

2 

ERASMUS MEDICAL CENTER, Department of ENT-Surgery (Audiology), 


3 

ERASMUS MEDICAL CENTER, Department of Ophthalmology, Rotterdam, 

Netherlands 

4 

ERASMUS MEDICAL CENTER, Medical Statistics, Rotterdam, Netherlands 

Purpose: In Nasopharyngeal cancer (NPC), the aggressive nature of the 

disease and its treatment can affect both function and quality of life. In the 

Erasmus MC, high cumulative doses of radiation (81Gy) are applied to the 

primary by boosting by either brachytherapy (BT; T1T2 tumors) or by (frameless) 

stereotactic radiation therapy (SRT; T3T4 tumors). The first aim of the 

study is to analyze late side-effects by QoL questionnaires. The second part 

deals with 3-D dose distributions in the cranial nerves and in other organs at 

risk (OAR). In this regard, in particular hearing loss is a frequently reported 

late side-effect. 

Materials: Between 2000 and 2005, 47 NPC patients (mean age 53 yrs; 

range 19 - 75) were treated according to protocol. That is 3 courses of neoadjuvant 

CHT (advanced disease, 32 patients) followed by 3DCRT (70Gy) 

and a boost. QoL was evaluated by 2 questionnaires (EORTC H&N-35 and 

MDADI) in cancer-free survivors with more than 1 yr FU. Eighty percent of 

NED patients agreed to be re-examined with special focus on the cranial 

nerves, ear- and eye functions. Hearing was measured by subjective audiometry 

and objectively by Brainstem Evoked Response Audiometry (BERA). 

Results: Five year LC and OS rates of 96% and 80% (T1,2) as opposed to 

78% and 60% (T3,4) were obtained. Grade 3 and 4 dysphagia was observed 

in 15% for H&N35, and in 10% for MDADI. Other side effects were xerostomia 

75%, sticky saliva 47%, and trismus 10%. Patients experienced a median 

[mixed] hearing loss in AD of 60 dB (range 7-73 [perceptive], 1-45 [conduc-


tive]) and in AS of 50 dB (range 12-63 [perceptive], -5-43 [conductive]). The 

hearing loss originated in the cochlea or n.VIII (BERA). 

Conclusions: QoL analysis revealed late side effects such as dysphagia, xerostomia 

and hearing deficits. Apparently for dysphagia and xerostomia the 

factor total dose (p=0.05), and for hearing, factors such as age [>50, p=0.02], 

Chemotherapy [Cisplatin yes; ns) and RT dose [>45Gy; ns], seem to play 

an important role. The total dose to be received by the cranial nerves and 

cochlea should be included as constraints in the treatment plan optimization 

(IMRT). As a preventative measure a CT/MRI based atlas (boxes), corresponding 

to the anterior- middle- and posterior cranial fossa of the base of 

skull, was developed for fast pre-treatment evaluation (Dmax) of the dose 

distributions in critical nerve structures and cochlea. 

817 poster 

NASOPHARYNGEAL CANCER TREATED WITH ACCELERATED 

RADIOTHERAPY IN COMBINATION WITH HYPOXIC MODIFICATION 

(NIMORAZOLE) AND WEEKLY CISPLATINUM. RESULTS FROM THE 

FIRST 45 PATIENTS TREATED ACCORDING TO THE DAHANCA 14 

GUIDELINES 

J. Bentzen 1 , J. Johansen 2 , C. Kristensen 3 , L. Andersen 4 , M. Overgaard 

5 , J. Overgaard 6 

1 

HERLEV HOSPITAL,, Dept of Oncology„ Herlev , Denmark 

2 

ODENSE UNIVERSITY HOSPITAL,, Dept of Oncology, Odense, Denmark 

3 

RIGSHOSPITALET,, Dept of Oncology, The Finsen Centre„ Copenhagen, 

Denmark 

4 

AALBORG HOSPITAL,, Dept of Oncology„ Aalborg, Denmark 

5 

AARHUS UNIVERSITY HOSPITAL,, Dept of Oncology„ Aarhus , Denmark 

6 

AARHUS UNIVERSITY HOSPITAL, Dept of Experimental Clinical Oncology„ 


Purpose: Purpose: To improve the treatment outcome for nasopharyngeal 

cancer (NPC) in Denmark, DAHANCA added in 2003 weekly concomitant cisplatinum 

to its slightly accelerated radiation treatment schedule (DAHANCA 

14 protocol). This analysis describes survival data, loco-regional control, and 

compliance to treatment. 

Materials: Material/Methods. Data from 45 patients who prospectively had 

been reported to the DAHANCA secretariat was obtained for the present analysis.This 

consisted of 32 men and 13 women, 3 with stage I disease, 10 stage 

II, 16 stage III, and 16 stage IV. 39 patients received radiation treatment with a 

curative intent with a prescription dose of 68 Gy in 2 Gy fractions, 6 fractions 

per week. The radiosensitizer nimorazole was given orally at a dose of 1200 

mg/m2 before each fraction. Concomitant cisplatinum (40 mg/m2 i.v.) was 

given once a week during radiotherapy for a maximum of 6 cycles. 

Results: Results. 35 patients received concomitant cisplatinum as per protocol. 

Compliance was good since 76 % of the patients received five cycles of 

cisplatinum or more, that is >200mg/m2. 3-year recurrence-free survival and 

overall survival rates were 72 % and 80 %, respectively 

Conclusions: Conclusion: In spite of accelerated radiotherapy to large head 

and neck volumes, compliance was good in this cohorte of nasopharyngeal 

cancer patients. Survival rates were high, and in agreement with other reports. 

However, the fraction of stage IV patients in this study was small. 

818 poster 

NECK DISSECTION IS NOT NECESSARY AFTER INDUCTION 

CHEMOTHERAPY FOLLOWED BY CONCOMITANT CHEMORADIA- 

TION IN PATIENTS WITH N2A-C M0 HEAD-AND-NECK SQUAMOUS 

CELL CARCINOMA 

S. Loo 1 , C. Beadsmoore 2 , C. Martin 1 , P. Montgomery 3 , T. Roques 1 

1 

NORFOLK AND NORWICH UNIVERSITY HOSPITAL NHS TRUST, Oncology, 

Norwich, United Kingdom 

2 

NORFOLK AND NORWICH UNIVERSITY HOSPITAL NHS TRUST, Radiology, 


3 

NORFOLK AND NORWICH UNIVERSITY HOSPITAL NHS TRUST, ENT, 


Purpose: The role of neck dissection in the management of neck metastases 

in patients with stage N2A-C head-and-neck squamous cell carcinoma 

(HNSCC) remains undefined. [18F]-fluorodeoxyglucose positron emission 

tomography/computed tomography (FDG PET/CT) has been used to select 

patients for neck dissection after curative radiotherapy. With the addition of 

induction chemotherapy to radiotherapy and concomitant chemotherapy, a 

complete response will be achieved in a high proportion of patients. The aim 

of this study is to determine whether neck dissection is necessary in patients 

treated with this strategy. 

Materials: Between April 2005 and September 2007, 37 patients with stage 

N2A-C M0 HNSCC were treated with curative intent using a non-surgical approach. 

Treatment for this group of patients in our institution is induction 

chemotherapy with up to 3 cycles of cisplatin and 5-fluorouracil followed by 

radical radiotherapy with concomitant platinum-based chemotherapy. FDG- 

PET/CT is performed 3 months after completion of treatment. Neck dissection 

is carried out only in those patients with a PET scan that shows increased 

tracer uptake in the neck or when there is high clinical suspicion of residual 

disease. Those with a negative PET are observed. (Prior to April 2005, treatment 

would have involved performing a planned neck dissection following 

chemoradiation, which is the current standard practice in the United Kingdom). 

Results: 9 patients had N2A, 18 had N2B and 10 had N2C disease. The 

primary tumour sites were oropharynx (31), hypopharynx (2), nasopharynx 

(1) and unknown primary (3). 34 patients received induction chemotherapy. 

29 received radiation with concomitant platinum-based chemotherapy. Only 

1 patient had residual cervical lymphadenopathy showing increased FDG uptake. 

That patient underwent a neck dissection but no residual cancer was 

present on pathologic assessment. The remaining 36 were observed without 

neck dissection. At a median follow up of 12.2 months, no regional recurrence 

has been identified. PET has a negative predictive value of 100%. 

Conclusions: Induction chemotherapy with cisplatin and 5-fluorouracil followed 

by radical radiotherapy with concurrent platinum-based chemotherapy 

is an effective regimen for the management of neck metastasis in patients 

with stage N2A-C M0 HNSCC. No regional failures have occurred and neck 

dissection can thus be safely withheld. FDG PET/CT performed 3 months after 

the completion of treatment can provide accurate assessment of treatment 

response. Longer follow-up will be needed to confirm our findings. 

819 poster 

NUTRITIONAL COUNSELLING IN HEAD AND NECK CANCER 

PATIENTS UNDERGOING RADIOTHERAPY: RESULTS OF A LONGI- 

TUDINAL STUDY 

F. Marazzi 1 , G. E. Martorana 2 , M. Bossola 3 , C. Iannattone 1 , G. Mantini 

1 , M. C. Mele 2 , F. Miccichè 1 , L. Nardone 1 , S. Silipigni 1 , V. Valentini 1 

1 

CATHOLIC UNIVERSITY, Department of Radiotherapy, Rome, Italy 

2 

CATHOLIC UNIVERSITY, Department of Biochemistry and Clinical Biochemistry 

Institute, Rome, Italy 

3 

CATHOLIC UNIVERSITY, Department of Surgical Science, Rome, Italy 

Purpose: To evaluate the effect of nutritional counselling on toxicity, nutritional 

status and quality of life in patients undergoing radiation therapy for 

head and neck cancer. 

Materials: Between Aug 2007 and Feb 2008 all patients with head and neck 

cancer candidates to radiotherapy concurrent to chemotherapy (cisplatin or 

cetuximab) were considered eligible. Before the start of RT-CT and twice a 

week patients received nutritional counselling. A highly palatable oral supplement 

(dissolvable hydrolysed proteins with high biological value and alphalinolenic 

fatty acid) was added to diet. Toxicity was evaluated weekly according 

to CTC v3.0. 

Results: 19 patients were included in the study (mean age 56.1±9.9 years; 

16 males and 3 females). 6 patients were treated with 3D conformal RT 

and 13 with IMRT. The total dose was 70 Gy with conventional fractionation 

(12 cases) or 66 Gy with accelerated fractionation using SIB (7 cases). All 

patients completed RT. Mucositis G3 was present in 36.8% of the cases. Only 

patients treated with cetuximab (n=11) developed skin dermatitis G3/4 (G3, 5 

and G4, 2 cases). All patients who received cetuximab developed acne (in 2 

cases, G3). Dysphagia G3 was present in 47% of patients. In 6/19 patients, 

interruption ≥6 days was needed whereas in 9 was

the end; p=0.36) as well as the transferrin levels (mg/dl) (224.5±55.6 at the 

start and 212±53.3 at the end; p=0.41). BCAA levels (mmol/l) remained 

stable during RT (536.3±134 at the start and 500±110 at the end; p=0.62) 

as well as the LNAA (705±188 at the start and 660±144 at the end; p=0.64). 

The tryptophan levels decreased significantly (82.1±27.6 at the start and 

41.1±11.9 at the end; p 50 days in 62% (33) of the patients. Thirty two percent (17) of the patients 

required tracheostomy before or during concurrent CRT. Percutaneous 

endoscopic gastrostomy was placed in 80% (43). 

Results: Kaplan Meier estimate for 3 year disease free survival (DFS) was 

65% (95%CI;24.7 -37.2). On univariate analysis grade ( well vs moderate/poor, 

p=0.04), presence of tracheotomy (yes vs no, p= 0.03) and prolonged 

radiotherapy treatment time (< 50 days vs > 50 days, p= 0.04) had 

a significant negative influence on DFS survival. Age (< 50 yrs vs > 50 yrs, 

p=0.64), sex (males vs females, p=0.14), smoking ( smokers vs non smokers, 

p=0.46), stage (III vs IV, p=0.12) and subsite (supraglottis vs glottis p=0.57) 

did not influence survival. On multivariate analysis no factor was significant. 

Conclusions: Results of laryngeal preservation with concurrent chemoradiation 

in our population are comparable to reports from western literature. Prolonged 

radiation treatment time, presence of tracheotomy and high tumour 

grade have a negative influence on survival in these patients. 

822 poster 

OUTCOME OF T1N0M0 SQUAMOUS CELL CARCINOMA OF THE 

LARYNX WITH SHORT COURSE RADIOTHERAPY 50 GRAY IN 16 

FRACTIONS: THE BIRMINGHAM EXPERIENCE 

N. Cheah 1 , S. Lupton 1 , A. Marshall 2 , A. Hartley 1 , J. Glaholm 1 

1 QUEEN ELIZABETH HOSPITAL, UNIVERSITY HOSPITAL BIRMINGHAM NHS 

FOUNDATION TRUST, Cancer Centre, Birmingham B15 2TH, United Kingdom 

2 THE UNIVERSITY OF WARWICK, Warwick Medical School Clinical Trials 

Unit, Coventry CV4 7A, United Kingdom 

Purpose: To review results of hypofractionated radiotherapy in T1N0M0 

squamous cell carcinoma of the larynx. 

Materials: A series of 100 patients treated with radiotherapy from 1993 until 

2001 was reviewed. Median age was 67 years. Median follow up was 7 years 

(range 3-14 years). Radiotherapy was delivered to a total dose of 50 Gray 

in 16 fractions treating daily, 5 days a week over 21 days. The radiotherapy 

fields used were either 2 wedged lateral parallel opposed or anterior oblique 

fields. 

Results: Loco-regional control rates with radiotherapy alone were 92% at 

2 years and 88% at 5 years. Following salvage surgery, the ultimate locoregional 

control rate was 96%. The relapse-free survival rates at 2 and 5 

years were 85% and 70%. The cause-specific survival rates at 2 and 5 years 

were 99% and 97%. The median overall survival was 11 years and overall 

survival rates at 2 and 5 years were 91% and 76%. Second primary cancers 

occurred in 21% of patients, primarily in the lung and prostate. 

Conclusions: Primary radiotherapy using 50 Gray in 16 fractions for T1N0M0 

squamous cell carcinoma of the larynx offers high loco-regional control rates 

with voice preservation. These results from a hypofractionated radiotherapy 

schedule are comparable to other longer fractionation schedules and offer 

potential for optimising resource usage. In the event of local relapse, salvage 

surgery still offers good loco-regional control.


823 poster 

P53 EXPRESSION IN PATIENTS WITH NASOPHARYNGEAL CAN- 

CER 

C. Demiroz 1 , O. Saraydaroglu 2 , L. Ozkan 2 , O. Yerci 1 

1 

ULUDAG UNIVERSITY MEDICAL COLLEGE, Radiation Oncology, Bursa, 

Turkey 

2 

ULUDAG UNIVERSITY MEDICAL COLLEGE, Pathology, Bursa, Turkey 

Purpose: The aim of this study was to observe the clinical and histopathological 

relation of the p53 gene expression in primary nasopharyngeal cancers 

and its effect on survival and local control 

Materials: We retrospectively assessed 21 nasopharynx cancer patients 

those have been treated in Uludag University Muammer Agim Radiotheraphy 

Center during 1997-2005 and whose paraffin block samples were available. 

Sixteen (76%) of our patients were male. Median age was 51 (18-67) and 9 of 

the patients (43%) were younger than 50. Distributions by tumor stage were 

evaluated as follows; T2a 7 patients, T2b 3 patients, T3 2 patients, and 9 patients 

were T4. Nodal stage distributions were; 5 N0 patients, 3 N1 patients, 

10 N2 and 3 N3 patients. Histologically 7 patients (33%) had squamous cell 

carcinoma, 13 (67%) had indifferentiated carcinoma and 1 patient could not 

be histologically typed. External RT was applied at 180-200 cGy/fx at a total 

of 70-72 Gy. Six patients had brachytherapy with HDR Ir-192 source at 

7 Gy/fx once after external RT. The paraffin blocks of the patients were evaluated 

immunohistochemically for p53 expression and dyed areas over 5% 

were regarded as positive. Impact on survival was analyzed by Kaplan-Meier 

log rank test. Correlations of variables were analyzed by Spearman’s correlation 

analysis. Statistical analyses were achieved by SPSS and p values 

below 0,05 were accepted as statistically significant. 

Results: The mean value for follow-up period is 38 months, while median 

value is 36 months. 5 years survival in the study group is 48%, while metastasis 

free 5 years survival is 46%. At the endoscopic examination 14 patients 

(70%) were found to have complete response, 2 patients (10%) had 

no regression and 5 patients (20%) had no record of final evaluation. We 

determined complete response and nearly complete response in 12 patients 

(57%), partial response in 1 patient (5%) and stable disease in 5 (20%) patients 

in radiologic evaluation. Six patients (29%) had metastases during 

follow-up period. Eight of the patients (38%) were still alive, 11 were (52%) 

dead and we could not contact 2 of the patients. P53 positive in 13 patients 

and analyses showed no relation between P53 and survival and local control. 

Other analyses on survival; patients with high performance status were 

significantly were more likely to survive longer (p=0.01). Survival in patients 

those received adjuvant chemotheraphy were longer than those who did not 

(p=0.01). Although patients who received concomitant chemoradiotherapy 

also had longer survivals, this was not statistically significant. Patients who received 

adjuvant CT (p=0.020), and also female patients (p=0,07) were found 

to have a lower rate of metastasis. All patients with endoscopically complete 

regression had longer survivals (p=0,07). 

Conclusions: The results of our study did not show statistically significant 

relation between p53 over expression and survival and loco-regional control 

in nasopharynx cancer patients treated with radiochemotheraphy. 

824 poster 

PALLIATIVE PDR BRACHYTHERAPY IN TREATMENT OF RECUR- 

RENT LARYNX CANCER 

J. Skowronek 1 , A. Chichel 1 , M. Kubaszewska 1 , M. Kanikowski 1 , G. 

Zwierzchowski 2 , M. Fundowicz 1 



Purpose: A large majority of patients with recurrences of larynx cancer are 

disqualified from radical treatment and constitute a group of bad prognosis. 

Some of them can be qualified for salvage surgery and treated mostly with a 

palliative intent. In some cases brachytherapy can be a treatment of choice 

after previously applied external beam radiotherapy. The paper is to present 

results of PDR interstitial brachytherapy (PDR BT) in a described group of 

patients. 

Materials: Thirty eight patients with recurrent larynx cancer were treated with 

PDR - BT since October 2000 till September 2005 in Greatpoland Cancer 

Center. The age of patients ranged from 41 to 79 years, average 59,5 years. 

The group consisted of 5 women (13,2%) and 33 men (86,8%). Clinical locations 

of tumor before PDR BT were: metastasis in loco regional lymph 

node system (n=22, 57.9%), recurrence in trachestomy area (n=14, 36.8%) 

and infiltration of surrounded organs (n=2, 5.3%). In 37 cases squamous cell 

carcinoma, in one case adenocarcinoma were diagnosed. 29 patients were 

previously both operated and irradiated (76.3%), 3 were irradiated (7.9%) and 

6 were operated (15.8%) as a single modalities. Primary lesions were irradiated 

most frequently with total dose of 70 Gy. Median time between primary 

tumor and its recurrent appearance was 15.5 months (min. 3 and max. 48 

months) and it was longer than 12 months in 18 cases. Recurrences were 

treated up to total dose of 20 Gy, most commonly with a single fraction of 

20 Gy in 25 pulses by 0.8 Gy hourly. In 5 cases PDR fraction was repeated 

in view of small size of a tumor and relative good response after first fraction. 

In 6 cases hyperthermia was added. The assessment of the results was 

performed in 1st months after completion of the treatment and then after 3, 

6 and 12 months. Tolerance of the treatment and acute complications are 

discussed. 

Results: Median survival time carried out 5.3 months (1 8 months). In 1st 

month after the end of the treatment complete remission (CR) was found 

in 3 (%), partial remission (PR) in 25 (%) and lack of remission (NR) in 10 

(16.7%) cases, respectively. In 3rd and 6th months remission (CR + PR) 

was observed in (%) and (%) patients, respectively. In 14 cases superficial 

necrosis was observed in first and third months of observation. 

Conclusions: 1. PDR brachytherapy can be a treatment of choice in patients 

previously irradiated with external beam radiotherapy and/or surgery. 

2. It appears to be, that in case of infiltrating the tracheostomy area PDR 

brachytherapy can prolong overall survival time. 3. To confirm the above a 

comparative investigation of a larger group of patients is needed. 

825 poster 

PAROTID LYMPH NODES METASTASES FROM SKIN CARCINOMA 

-TREATMENT BY RADIOTHERAPY 

B. Jancar 1 

1 INSTITUTE OF ONCOLOGY, Radiotherapy, Bucharest, Romania 

Purpose: Squamous cell carcinoma of the skin in the H&N area, especially if 

located on the scalp, in temporal and frontal area frequently metastasizes 

to lymph nodes in the parotid area. Metastases are most often treated 

by surgery. Patients with inoperable metastases or those who are unfit for 

surgery are treated with irradiation.Our aim was asses the efficiency of treatment 

of metastases to the parotid area with irradiation. 

Materials: From 1986 to 2006, 23 pts with metastases from skin carcinoma to 

parotid lymph nodes were treated with irradiation. There were 13 female and 

10 male pts. The patients were of advanced age, median age was 81,6 years 

(from 68 to 90 years) with several concomitant diseases. They were unfit for 

surgery because of advanced age and poor physical condition, so irradiation 

was the treatment of choice. In some patients more than one location of 

previously treated skin carcinoma could be the source of metastases, but it 

could not be determined which one of them is the culprit. They were irradiated 

with the dose equivalent of 70 Gy. 

Results: In all patients complete regression was observed. All survivors were 

followed for more than one year. In 3 patients progression outside the treatment 

area occured within the first year after treatment and 4 other patients 

died of unrelated diseases.Two to six years after the completed therapy, 16 

patients were alive and NED. 

Conclusions: Radiotherapy is very effective treatment for local control of 

lymph nodes metastases in the parotid area even if patients are in poor condition 

and unfit for surgery. Photograps of patients before and after treatment 

will be presented 

826 poster 

PAROTID-SPARING IMRT - WHERE EXACTLY IS THE PAROTID ? 

T. Roques 1 , S. Loo 1 , P. Smith 1 , C. Martin 1 , S. Cherian 1 

1 NORFOLK AND NORWICH UNIVERSITY HOSPITAL NHS TRUST, Oncology, 


Purpose: IMRT for oropharyngeal cancer aims to keep the contralateral 

mean parotid dose below 24Gy to preserve unstimulated salivary gland function. 

In practice the mean dose accepted is usually within 10% of this figure 

as trying to reduce the dose further risks under-dosing the PTV. An oncologist

contours the parotid in each patient. This study assesses the inter-observer 

variability in parotid contours and the impact this may have on the IMRT solution. 

Materials: CT datasets (without contrast) from 10 patients with oropharyngeal 

cancer who had been treated with IMRT were anonymised. 12 subjects 

(3 radiologists, 4 oncologists and 5 dosimetrists) were given relevant clinical 

information and access to diagnostic imaging for each patient. They were 

asked to contour the parotid gland that had been spared with IMRT. They 

rated their confidence in the contours drawn on a Likert scale (0-10). The 

DVH for each study parotid contour was calculated using the IMRT plan actually 

delivered for that patient. This was compared to the original DVH obtained 

when the plan was used clinically. 

Results: The mean parotid dose achieved during the actual treatment ranged 

from 22.1 to 25.2Gy (all within 10% of 24Gy). Using the study contours, the 

mean parotid dose obtained was within 10% of 24Gy for only 53% of oncologist 

volumes, 55% of radiologist volumes and 52% of dosimetrist volumes. 

Mean dose was within 20% of 24Gy for 80%, 90% and 92% of the volumes 

respectively. No significant differences were noted between the groups apart 

from radiologists contouring faster (8 vs 15 mins) and more confidently (8 vs 

5 on a Likert scale) compared to oncologists or dosimetrists. 

Conclusions: Inter-observer variability in parotid contours is clinically significant. 

Different parotid contours can change the parotid DVH to a point where 

a different plan would have been produced to achieve a mean dose of less 

than 24Gy. This may in turn result in a change in dose to the PTV. Consensus 

guidelines on parotid contouring are therefore needed so that parotid 

DVHs can be translated into the clinical endpoint of salivary sparing between 

institutions or within clinical trials. 

827 poster 

PARTICLE THERAPY FOR MUCOSAL MALIGNANT MELANOMA OF 

THE HEAD AND NECK: A RETROSPECTIVE STUDY 

D. Miyawaki 1 , M. Murakami 1 , Y. Oda 1 , Y. Demizu 1 , R. Sasaki 2 , Y. 

Hishikawa 1 , K. Sugimura 2 

1 HYOGO ION BEAM MEDICAL CENTER, Radiology, Tatsuno, Japan 

2 KOBE UNIVERSITY GRADUATE SCHOOL OF MEDICINE, Radiology, Kobe, 

Japan 

Purpose: Mucosal malignant melanoma (MMM) of the head and neck is resistant 

to conventional photon (X-ray or gamma-ray) radiotherapy. Particle 

therapy including proton therapy and carbon-ion therapy may be useful for 

the treatment of MMM because of its ability to deliver high dose to tumors 

while minimizing the dose to risk organs. Moreover, carbon-ion is supposed 

to be effective against MMM according to the results of biologic experiments. 

The purpose of this study was to assess the efficacy and toxicity of particle 

radiotherapy for MMM of the head and neck at Hyogo Ion Beam Medical 

Center (HIBMC) retrospectively. 

Materials: Between February 2002 and August 2006, 48 patients with MMM 

of the head and neck were treated with particle therapy. Twenty five of 48 

patients had no treatment before the particle therapy, whereas 8 had undergone 

surgery and chemotherapy, 7 surgery only, 7 chemotherapy only, and 

1 photon radiotherapy. Thirty six patients received proton therapy of 65 GyE 

in 26 fractions and 12 patients received carbon-ion therapy of 57.6 GyE in 

16 fractions. Primary tumor sites were nasal cavity in 26, maxillary sinus in 

5, ethmoid sinus in 5, palate in 5, and others in 7. Corresponding T-stages 

were T1 in 6, T2 in 10, T3 in 17, and T4 in 13. Overall and progression-free 

survivals, and local control were evaluated using the Kaplan-Meier method. 

Acute and late morbidities were assessed based on the Common Terminology 

Criteria for Adverse Events (CTCAE) v3.0. The median follow-up was 17 

months (range, 4-45 months). 


S 265 

Results: The 2-year overall survival and progression-free survival rates were 

53% and 25%, respectively. Six patients experienced local recurrence and 

the 2-year local control rate was 87%. Thirty three patients experienced distant 

metastases (lymph node, bone, lung, etc.). Within 1 year, 25 patients 

(52%) developed distant metastases. Grade 3 acute reactions were observed 

in 16 patients (mucositis in 12, dermatitis in 2, and otitis media in 2); however, 

no patients discontinued the treatment. Grade 4 late adverse effect was observed 

in 1 patient (visual loss). 

Conclusions: Particle radiotherapy showed favorable outcome for local control 

of MMM of the head and neck. As for distant metastasis, however, 

even the patients with early stage MMM (T1-2) developed multiple metastases 

even though the primary tumors are controlled. The current multidrug 

chemotherapy has limited effects on distantly recurred patients and good 

treatment to address this problem is awaited. 

828 poster 

POSTOPERATIVE RADIOTHERAPY TO PATIENTS WITH MAJOR 

SALIVARY GLAND CANCER 

J. Noh 1 , Y. C. Ahn 1 , W. Park 1 , H. Y. Kim 1 , C. H. Baek 2 , Y. I. Son 2 , H. S. 

Jeong 2 

1 

SAMSUNG MEDICAL CENTER, Radiation Oncology, Seoul, Korea Republic 

of 

2 

SAMSUNG MEDICAL CENTER, Department of Otolaryngology-Head and 

Neck Surgery, Seoul, Korea Republic of 

Purpose: This retrospective study analyzed treatment results of surgical resection 

and adjuvant radiation therapy (RT) in patients with major salivary 

gland cancer. 

Materials: Between March 1995 and January 2006, 75 patients received 

surgical resection and adjuvant RT for primary major salivary gland cancer. 

Complete resection was attempted in all patients and any type of neck dissection 

was performed in 27 patients (36.0%). All had one or more of following 

risk factors for recurrence: high-grade histology; positive or close (


- symptomatic NG tube). 16(31%) did not receive any form of enteral feeding. 

This differs from only 11% of pts in the Bonner trial with gr. 3-5 wt loss, 

CTCv3.0. Average wt loss was 2.63% (range -8.9 to +8.3) with a PG tube, 

vs. 9% (-14.1 to +3) with a SG tube, p=0.001. No one with a PG tube had a 

wt loss of >/10%, vs. 7/12 (58%) witha SG tube. The highest % wt loss with 

a PG tube was 8.9%, seen in 1 pt, vs. 14.1% in the other group. 7 pts with a 

SG tube lost more wt than the highest documented value of wt loss in the PG 

group, Table 1. 13/23 (56%) with a PG tube stayed in hospital for >4days after 

completing XRT, vs. 10/12 (83%) in the other group. This was due to grade 3 

mucositis and XRT-induced skin dermatitis. Minor complications occurred in 

12/23 (52.2%) with a PG tube, vs. no complications in the other group. The 

complications were leakage, local infection and a need for tube replacement 

in 7/23 pts. 

Conclusions: This study shows average wt loss with XRT and cetuximab 

was higher than the Bonner trial. It shows those with a PG tube lost significantly 

less wt, never losing >/10% body wt. These pts had a shorter hospital 

stay. Minor complications seen were likely due to a longer duration of tube 

insertion. 

830 poster 

RADIATION-INDUCED OPTIC NEUROPATHY: DOSE RESPONSE 

AND MODELING TOTAL DOSE AND FRACTIONATION. 

N. Bhandare 1 , W. Song 1 , V. Moiseenko 2 , M. Robert 1 , W. Mendenhall 1 

1 UNIVERSITY OF FLORIDA, Radiation Oncology, Gainesville, FL, USA 

2 VANCOUVER CANCER CENTER, Vancouver, USA 

Purpose: To evaluate the effects of total radiation dose received by the optic 

nerve and fractionation schemes (once daily [QD] and twice daily [BID]) on 

the risk of radiation-induced optic neuropathy (RION). 

Materials: Dose response (TD5, NTCP55, NTCP60) of the optic nerve was 

established by fitting incidence of RION to a logistic function. Also α/β was 

estimated by fitting a logistic function based on linear quadratic formalism to 

dose response. The maximum likelihood method was used to optimize the fit 

in both analyses. A comparison of 3 data sets on RION from the literature 1-3 

was carried out using the results obtained by (a) dose response modeling on 

3 data sets with (b) reported percentage incidence in the datasets, (c) Cox 

regression analysis, and (d) Kaplan-Meier product limiting actuarial analysis. 

Results: The incidence of RION increases with the total dose received by 

a segment of the optic nerve as indicated by the logistic modeling of dose 

response as well as the Cox regression analysis and Kaplan-Meier actuarial 

analysis. The logistic modeling of the 3 datasets indicates that the ranges for 

the combined data (QD+BID) are: TD5,52-57 Gy; NTCP55, 2.5-5.7%; and 

NTCP60, 6.5-11.1%. Based on the actuarial analysis, the 5-year probability 

of incidence varies from 3-5% for doses 60Gy. A 

Cox regression analysis indicated that fractionation was marginally significant 

(p=0.05-0.09). The actuarial analysis estimated the 5- and 10-year incidence 

for doses >60 Gy for QD was 21% and 23% and for BID it was 8% and 8%, 

respectively. 1 The logistic modeling for one of the datasets 1 estimated the 

following for the QD and BID data: TD5, 50 Gy and 66.3 Gy; NTCP55, 7.3% 

and 2.8%; and NTCP60, 9.9% and 3.6%, respectively. The estimated α/β for 

RION was 1.6 Gy 3 and 1.76 Gy. 1 

Conclusions: While the risk of RION increases with an increase in the total 

dose received by a segment of the optic nerve or optic chiasm, a threshold 

total dose to limit the incidence of RION cannot be determined from the 

limited data available in the literature. The decision to limit the dose to any 

segment of the optic nerve should be based on all of the available information 

including: (a) the information obtained from modeling, (b) the percent incidence 

in clinical data, (c) the Cox regression analyses, and (d) the actuarial 

analyses. Hyperfractionation indicates promise in reducing the incidence of 

RION. Reference List 1. Bhandare N et al. Does altered fractionation influence 

risk of radiation-induced optic neuropathy? Int J Radiat Oncol Biol 

Phys 2005;62:1070-1077. 2. Parsons JT et al. Radiation optic neuropathy 

after megavoltage external-beam irradiation: analysis of time-dose factors. 

Int J Radiat Oncol Biol Phys 1994;30:755-763. 3. Jiang GL et al. Radiationinduced 

injury to the visual pathway. Radiother Oncol 1994;30:17-25. 

831 poster 

RADIOTHERAPY FOR SINONASAL SQUAMOUS CELL CARCINOMA 

N. Jang 1 , H. G. Wu 1 , C. I. Park 1 

1 SEOUL NATIONAL UNIVERSITY OF COLLEGE OF MEDICINE, Department of 

*Radiation Oncology, Seoul, Korea Republic of 

Purpose: To evaluate the clinical outcome of radiotherapy for malignancies 

of the nasal cavity and maxillary sinus. 

Materials: Between May 1990 and July 2004, 81 patients with histologically 

proven squamous cell carcinoma of the maxillary sinus (n = 61) or nasal cavity 

(n = 20) were treated with postoperative (n = 36), or primary (n = 45) radiotherapy, 

using conventional or two-dimensional (n = 69) or three-dimensional 

conformal (n = 12) techniques. The median radiation dose was 66.6 Gy. Median 

age at diagnosis was 58 years (range, 19-83 years) and 78% of patients 

were male. Eighty-eight percent (postoperative, 83%; primary, 91%) of patients 

had T3 or 4 tumors and 88% of patients had N0 neck. Elective neck 

irradiation of the cervical lymph nodes was performed in 2 patients. Histologic 

grade was available only in 36 patients, and well, moderate, poorly differentiated 

squamous carcinoma were 14, 14, and 8 cases, respectively. Resection 

margin status was available in 30 patients, and R0, R1, and R2 resection 

was performed in 12, 10, 8 patients, respectively. Chemotherapy was used in 

54% of patients and most of them received 3 cycles of neoadjuvant 5-FU and 

cisplatin. 

Results: Median follow-up was 29 months (range, 4187 months) for all patients, 

and 92 months (range, 17187 months) for patients still alive at the last 

follow-up date. In all patients, the 5-year overall, local recurrence free, and 

disease-free survival rates were 41%, 51%, and 43%, respectively. In postoperative 

setting, the 5-year overall, local recurrence free, and disease-free 

survival rates were 46%, 57%, and 57%, respectively. With primary radiotherapy, 

the 5-year overall, local recurrence free, and disease-free survival rates 

were 36%, 47%, and 32%, respectively. Seventy-five percent of recurrences 

were developed within 18 months of follow-up and only 7% of recurrences 

were developed after 3 years of follow-up. Sixteen (20%) of all 81 patients 

and 10 (14%) of 71 originally N0 patients developed a regional failure in the 

neck. Most of regional recurrences were developed at ipsilateral level I (n=5), 

II (n=6), and contralateral level II (n=6). Distant metastasis occurred in 13 

patients and major site of failure were lung (n=10) and bone (n=9). The 5year 

overall survival rates of T1, 2, 3, 4 patients were 50%, 57%, 45%, and 

37%, respectively. Advanced stage was the most important prognostic factor 

on multivariate analysis in all patients. In postoperative cases, gross residual 

disease after surgery and positive lymph node were significant adverse factor 

of survival. With primary radiotherapy, complete response after radiotherapy 

was significant good prognostic factor of survival in multivariate analysis. 

Most of acute complication was grade 1-2 mucositis and dry mouth. 

Conclusions: In sinonasal squamous cell carcinoma, local failure was dominant 

cause of failure. However, in our series, 14% of regional recurrence was 

developed in initially N0 neck. To improve treatment outcome, aggressive 

local treatment with elective irradiation to upper neck may be considered.

832 poster 

RATES OF INVOLVEMENT FOR EACH NECK NODAL LEVEL IN 

PATIENTS WITH EARLY T-STAGE/ NODE-POSITIVE OROPHARYN- 

GEAL CARCINOMA 

G. Sanguineti 1 , J. Califano 2 , J. Zhou 1 , E. Stafford 2 , W. Koch 2 , R. Tufano 

2 , C. Gourin 2 , S. Marur 3 , A. Forastiere 3 

1 JOHNS HOPKINS, Radiation Oncology, Baltimore, USA 

2 JOHNS HOPKINS, Department of Head and Neck, Baltimore, USA 

3 JOHNS HOPKINS, Medical Oncology, Baltimore, USA 

Purpose: To describe the prevalence of pathological ipsilateral neck nodal 

involvement of for early T-stage/node positive oropharyngeal carcinoma. 

Materials: We retrospectively identified all of the patients that underwent upfront 

neck dissection for oropharyngeal squamous cell carcinoma at Johns 

Hopkins (JH) as part of their initial management in the last 10 years. We 

further selected the patients that fulfilled all of the following criteria: 1. early 

clinical T-stage (cT1-2); 2. cN+ at presentation; 3. no previous/synchronous 

tumors; 4. no previous excisional biopsy or ‘neck violation‘; 5. multi (3+) level 

neck dissection at JH; 6. neck specimen processed by surgical levels. For 

patients with bilateral neck nodes (N=8), only the site of dominant/presenting 

disease was considered. From the pathology report, we extracted the prevalence 

rate of involvement of levels I-V. 

Results: 103 patients met the criteria. Most of patients had primary tumors 

in the tonsil (N=72, 70%) or the base of tongue (N=26, 25%). cT-stage was 

as follows: T1, 58 pts (56.3%); T2, 45 pts (43.7%). Neck surgery consisted 

in radical neck dissection (RND) in 15 pts (14.6%), modified RND in 73 pts 

(70.9%) and selective neck dissection in 15 pts (14.6%). As result, level I, II, 

III, IV and V had been dissected in 95, 103, 103, 100 and 92 pts, respectively. 

The rate of pathological involvement of each level was 9.5%, 91.3%, 40.8%, 

18.0% and 3.3% for levels I-V, respectively. 77 pts (74.7%) had disease confined 

to levels II and/or III. Isolated involvement of levels I or IV was observed 

in one case each; no patient had isolated involvement of level V. 

Conclusions: In this contemporary series of patients with node positive/early 

T stage oropharyngeal cancer, of the patients have nodal disease confined 

to levels II and/or III. Level IV is at high risk of involvement, while levels I and 

V are at low risk. These prevalence rates provide the basis for computing 

the risk of subclinical disease in the neck that is negative on imaging; clinical 

implications will be discussed. 

833 poster 

REPLANNING THE IMRT TREATMENT ON DIFFERENT CT SCANS 

FOR HEAD AND NECK CANCER: IS THERE AN OPTIMAL TIMING 

FOR NEW SCANNING DURING TREATMENT? 

N. Dinapoli 1 , G. C. Mattiucci 1 , M. Balducci 1 , P. Bonomo 1 , B. De Bari 1 , 

M. De Santis 1 , F. De Rose 1 , A. Fiorentino 1 , S. Patriccioli 1 , C. G. Rinaldi 

1 , V. Valentini 1 

1 RADIOTERAPIA, Radiologia, Policlinico A. Gemelli, ROME, Italy 

Purpose: In RT for H&N malignancies the mucositis is one of the most important 

side effects and it can often led to weight loss for problems in feeding. 

There are evidences in literature that optimal dose distribution can be modified 

by changes in morphology of the patients due to weight loss and it could 

led to a potential growth of side effects or unpredictable dose distribution. In 

this study we investigated the possibility to optimize the IMRT treatments during 

the course of therapy using multiple CT scans and treatment plans (TPs) 

in order to adapt the therapy to modifications in weight of patients and find 

the moment when this replanning has to be performed. 

Materials: A retrospective analysis on 22 pts with locally advanced H&N cancer 

treated with IMRT was performed. Each patient underwent to a 1st simulation 

CT scan and a 1st TP was realized. Then, during treatment, each 

patient underwent to 2 further (20 pts) or 1 further CT scan (2 pts) in order 

to perform new TPs. All these TPs were realized by using a commercial 

treatment planning system (Eclipse, Varian). The further TPs were realized 

by copying the fluence maps from the starting TPs, and new dose distributions 

were simulated by normalizing the prescribed dose in order to obtain 

the same number of monitor units delivered with the 1st TP. So we obtained 

new dose distributions that simulated the changes in dose levels given by 

changes in the morphology of patients. Dose volume histograms (DVHs) 

were collected by each TP for the analysis of changes in dose distribution. 

Results: All patients had locally advanced H&N cancer including 3 nasopharynx, 

6 oropharynx, 2 hypopharynx and 11 larynx. DVHs were calculated in 

relative mode in order to compare different treatment schedules applied to 

different patients among themselves. A total number of 64 TPs on 64 different 

CT scans was performed. Results on changes in body hot spot values, 

spinal cord hot spot values, mean right, mean left parotid gland and mean 

parotid glands sum values are summarized in the table. 

Conclusions: The analysis of linear regression shows that there is a trend 

in increasing doses for spinal cord hot spot, body hot spot and parotid sum 

mean dose. In order to decrease the risk of unpredictable dose distribution 

and dose growth to critical structures a replanning can be scheduled considering 

the coefficient of linear regression lines and according to prescribed 

doses and local institutional protocols. 


834 poster 

S 267 

RESULTS OF EXTERNAL BEAM RADIATION THERAPY (EBRT) 

VERSUS EBRT AND "BOOST" BRACHYTHERAPY IN THE TREAT- 

MENT OF BASE OF TONGUE TUMORS. 

L. Takacsi-Nagy 1 , F. Oberna 2 , C. Polgár 1 , T. Major 1 , J. Fodor 1 

1 NATIONAL INSTITUTE OF ONCOLOGY, Budapest, Hungary 

2 BÁCS-KISKUN COUNTY HOSPITAL, Kecskemét, Hungary 

Purpose: To study the importance of high dose rate (HDR) boost brachytherapy 

(BT) after external beam radiation therapy (EBRT) of base tongue tumors. 

Materials: Between 1992 and 2005 ninety four patients with biopsy proven 

carcinoma of the base of tongue (T1-4N0-3M0) were treated with primary 

radiation therapy. For forty-four patients EBRT (mean dose, 61 Gy; range, 

50-66 Gy) with BT (mean dose, 17 Gy; range, 12-30 Gy; fraction number, 

1-8) and for fifty patients EBRT alone (mean dose, 63 Gy; range, 60-72 Gy) 

was given. 

Results: The median follow-up time for surviving patients was 95 months 

(range, 24-169 months). Boost BT increased the incidence of local tumor 

control (LTC) from 36 % to 59 % (p = 0.020). The 5-year probability of LTC 

was 56 % vs. 34 % (p = 0.029), the locoregional tumor control 47 % vs. 

31 % (p = 0.122) and the overall survival (OS) 50 % vs. 29 % (p = 0.028), 

respectively, in favour of the boost group. Serious, grade 4 radiation toxicity 

occurred in 14 % (6/44) and 8 % (4/50), respectively (p = 0.291). 

Conclusions: Boost HDR BT after EBRT improves LTC and OS significantly 

without considerable increase the risk of side-effects. 

835 poster 

RISK FACTORS REGARDING ESOPHAGEAL STRICTURE AFTER 

RADIOTHERAPY TREATMENT FOR HEAD & NECK CANCER. 

A. Ahlberg 1 , M. Al-Abany 2 , E. Alevronta 3 , P. Mavroidis 3 , S. Friesland 4 , 

A. Tilikidis 2 , B. Lind 5 , G. Laurell 6 

1 

KAROLINSKA UNIVERSITY HOSPITAL, Department of Otolaryngology, 


2 


3 

KAROLINSKA INSTITUTE, Medical Radiation Physics, Stockholm, Sweden 

4 


5 

KAROLINSKA INSTITUTE, Department of Oncology-Pathology, div of Clinical 

Cancer Epidemiology, Stockholm, Sweden 

6 

UMEÅ UNIVERSITY, Clinical Sciences, Umeå, Sweden 

Purpose: It is well recognized that many patients with head and neck carcinoma 

have problems with food intake and malnutrition. The purpose of 

this case-control study is to investigate the risk factors and irradiation doses 

that are associated with development of non-neoplastic stricture in the upper 

esophagus after external radiotherapy. 

Materials: This study is based on a sample 78 patients who received radiation 

treatment for head & neck cancer at Karolinska Hospital, Stockholm, 

Sweden. Of these patients 33 developed esophageal stricture and 45 were 

symptom-free and constituted a control group. The distribution of the groups 

of patients with and without stricture by the anatomical cancer site is: oral 

(15%, 12%), larynx (27%, 44%), hypopharynx (9%, 0%), oropharynx (30%, 

25%), epipharynx (9%, 4%), others (9%, 10%), respectively. For each patient 

the 3D dose distribution of the upper 5 cm of esophagus and the clinical 

treatment outcome were available. The analysis was conducted for the periods 

1991-2000, 2001-2005 and total due to a change of irradiation techniques 

over the years. Radiotherapy data are combined with clinical data extracted 

from the medical journals. 

Results: The mean and maximum doses to the upper 5 cm of esophagus 

were on average 49.9 (SD =12.8) and 61.2 (SD=7.9) Gy for patients with stricture, 

whereas they were 31.8 (SD =18.5) and 55.7 (SD =19) Gy for the control 

group. Stratifying the patients by treatment technique, the mean dose for patients 

with and without stricture was 49.8 (SD =14.1) and 21.4 (SD =14.1) 

for patients treated in the period 2001-2005; whereas the mean dose for patients 

with and without stricture was 49.9 (SD =12.6) and 45.9 (SD =14.2) of 

patients treated in the period 1991-2000. A statistically significant correlation 

between dose to the upper 5 cm of esophagus and the esophageal stricture 

was found. The Odds Ratio for the total group of patients receiving a mean


dose of 46 Gy or higher to the upper 5 cm of esophagus was = 6.3, 95 % CI 

= 2.3-16.9. Stratifying the patients by treatment time, the Odds Ratio was = 

35.7, 95 % CI = 4.2-333.3 for patients treated after 2000 and = 1.9, 95 % CI 

= 0.6-6.5 for patients treated before 2001. 

Conclusions: Larger mean and maximum doses to the upper 5 cm of esophagus 

characterize the group of patients with stricture compared to the group 

of patients without stricture. There is indication that a change in the irradiation 

technique decreased the risk for esophageal complications. However, 

data also indicates that development of esophageal stricture after radiotherapy 

might not only depend on the dose. We are currently investigating different 

clinical parameters that could be related to this complication. 

836 poster 

RISK OF DISTANT METASTASES IN POSTOPERATIVE RADIOTHER- 

APY OF 835 PATIENTS WITH LARYNGEAL CANCER 

A. Idasiak 1 , T. Rutkowski 1 , I. Wesolowska 2 , G. Wozniak 1 , R. Suwinski 1 

1 MARIA SKLODOWSKA - CURIE MEMORIAL CANCER CENTER AND 

INSTITUTE OF ONCOLOGY GLIWICE, Radiotherapy Department , Gliwice, 

Poland 


INSTITUTE OF ONCOLOGY GLIWICE, Department of Radiotherapy Treatment 

Planning, Gliwice, Poland 

Purpose: Laryngeal cancer is the most common head and neck malignancy. 

Postoperative radiotherapy in advanced laryngeal cancer reduces risk of local 

and regional recurrences. An improvement in local and regional control 

achieved by combined therapy results that distant metastases become an increasingly 

common case of treatment failure.The aim of the study is to evaluate 

the prognostic factors for the risk of distant metastases after postoperative 

radiotherapy for laryngeal cancer. 

Materials: Medical records of 835 patients (81 women, 754 men) with laryngeal 

cancer treated between 1980-2003 were analyzed. The age ranged 

from 35 to 78 (median 56). All patients had locally advanced squamous cell 

laryngeal cancer treated with surgery and postoperative radiotherapy. Locally 

advanced tomors (T3, T4) constituted 526 cases (63%). Positive lymph nodes 

were found in 371 of 835 cases (44%). The survival plots were estimated using 

the Kaplan-Meier method. A multivariate Cox proportional hazard model 

and logistic regression model was used to evaluated influence of the following 

variables on MFS and the ultimate risk of metastases: age, sex, localization, 

TN stage, HGB before and at the end radiotherapy, total radiation dose, dose 

per fraction, overall treatment time, interval surgery-radiation time, pathological 

margins and positive nodes in surgical specimen. 

Results: The crude incidence of distant metastases was 9% (78/835 pts). 

One year, 3-year, 5- year and 10-year actuarial metastases free survival 

were 95%, 88%, 86% and 81% respectively. The Cox regression analysis 

revealed two variables, which had significant and independent influence on 

metastases-free survival: localization of cancer (glottic vs. supraglottic) and 

number of positive lymph nodes at pathological staging. The lungs and bones 

were the most common sites of metastases (55% and 35% respectively), 

whereas metastases to liver (6%) and brain (4%) were rare. 

Conclusions: Distant metastases rate is important part of treatment failure 

in postoperative radiotherapy for patients with laryngeal cancer. In the presented 

group of patients it was 9% vs. 18% of local treatment failure. Number 

of positive lymph nodes in pathological specimen and site of primary cancer 

(glottic vs. supraglottic) significantly and independently predict risk of distant 

metastases in this set of patients with laryngeal cancer. 

837 poster 

SENSORINEURAL HEARING LOSS AFTER TREATMENT IN 

NASOPHARYNGEAL CARCINOMA: A QUANLITATIVE AND QUANTI- 

TATIVE LONGITUDINAL ANALYSIS 

S. H. Chan 1 , W. T. Ng 1 , K. L. Kam 2 , C. W. Choi 3 , T. K. Yau 1 , A. W. M. 

Lee 1 , S. K. Chow 2 

1 

PAMELA YOUDE NETHERSOLE EASTERN HOSPITAL, Clinical Oncology, 

Hong Kong, China 

2 

PAMELA YOUDE NETHERSOLE EASTERN HOSPITAL, Department of 

Otorhinolaryngology, Hong Kong, China 

3 

HONG KONG CANCER FUND, Hong Kong Cancer Fund, Hong Kong, China 

Purpose: To analyze the effects of chemotherapy and radiation in relation 

to sensorineural hearing loss (SNHL) development following contemporary 

treatment in nasopharyngeal carcinoma (NPC). 

Materials: Eighty-seven NPC patients were treated with radiotherapy or 

chemoradiotherapy using either three-dimensional conformal radiotherapy 

(3D-CRT) or intensity modulated radiotherapy (IMRT) technique between 

September 2004 and December 2005. Tympanometry and pure-tone audiogram 

(PTA) assessment were performed before radiotherapy and then serially 

at 6-month-interval. Dose volume data of the cochlea were analyzed. The effect 

of cisplatin delivered in concurrent or non-current phase was explored. 

Results: Among the 170 eligible ears, radiotherapy (n=30) and chemoradiotherapy 

(n=140) resulted in 40% (n=12) and 56.4% (n=79) persistent SNHL 

(>=15 dB loss) respectively after a median follow-up of 2 years. High tone 

loss was more frequent statistically in the chemoradiotherapy group than radiotherapy 

alone group (55% vs 33.3%, p

per fraction given to this volume was 2 Gy up to 60 Gy. The PTV1-ETV + 

4mm (electively irradiated volume) received dose per fraction 1.7-1.8 Gy up 

to 54-56 Gy. Overall treatment time was 6 weeks (5 fr/week, 30 fr.). Concomitant 

chemotherapy consisted of cisplatin in daily dose100mg/m 2 given 

two times during irradiation (1 and 22 day of treatment). The evaluation of 

early tolerance was performed once weekly during treatment and every 2 

months during the follow up. The early reactions were scored according to 

the EORTC/RTOG scale. Between Sept. 2006 and Jan. 2008, 38 patients 

with III and IV clinical stage of SCHNC were treated (24 oropharyngeal cancers, 

7 laryngeal cancers, 7 hypopharyngeal cancers). 

Results: The follow-up time ranged from 10 weeks to 16 months. No severe 

life risking complications were observed. G3 mucositis was noted in all patients, 

but area of this reaction was limited only to the boost volume. At the 

end of treatment extended reactions were observed as follows: G2 skin reactions 

8/38, moderate xerostomia 34/38, functional G3 mucositis 3/38. Extension 

of those reactions were decreased during follow up with recovery within 

2 months, except for xerostomia. Complete regression was observed in 37 / 

38 pts. Local recurrence was observed in one case. 

Conclusions: At present it might be concluded that accelerated radiotherapy 

with SIBIMRT given concomitantly with cisplatin is well tolerated as far as 

early tolerance are concerned. It might be expected that this method could 

produce better local control of the advanced SCHNC without increasing toxicity. 

840 poster 

SIMULTANEOUS MODULATED ACCELERATED RADIATION 

THERAPY (SMART) AND CONCOMITANT CHEMOTHERAPY IN 

EPITHELIAL TUMORS OF NASOPHARYNX AND OROPHARYNX . 

E. Dononi 1 , G. Frezza 1 , M. Palombarini 2 , A. Baldissera 1 , C. Degli Esposti 

1 , O. Martelli 1 , F. Monari 1 , F. Salvi 1 , F. Spagnolli 1 , P. Chiovati 2 , R. 

Romagnoli 2 

1 BELLARIA HOSPITAL, Radiotherapy, Bologna, Italy 

2 BELLARIA HOSPITAL, Medical Physics, Bologna, Italy 

Purpose: To assess the results of intensity modulated radiation therapy 

(IMRT) with simultaneous boost and concomitant chemotherapy in 29 patients 

(pts) with nasopharynx and oropharynx tumors after one year of follow 

up (fu). 

Materials: From January 2005 to March 2008 42 pts with carcinoma of the 

nasopharynx (13pts), of the oropharynx (25pts) or with metastases in cervical 

lymph nodes from unknown primary (4pts) have been treated with IMRT 

with simultaneous boost and concomitant chemotherapy. Pts were staged 

with fibroscopy of the upper respiratory and digestive tract, CT scan and, 

when appropriated, MR and PET scan. Stage of the disease at diagnosis 

was the following: Oropharynx: T1N+ 3 pts, T2N0 2 pts, T2N+ 9 pts, T3N0 

4 pts, T3N+ 4pts, T4N+ 3 pts. Nasopharynx: T2N0 1 pt, T2N+ 5pts, T3N+ 

3 pts, T4N0 2 pts, T4N+ 2 pts. Metastatic carcinoma in neck node with unknown 

primary TxN2b 3 pts, TxN3 1 pts. Patients were immobilized with a 

thermoplastic mask extending below the shoulder. A planning CT scan of the 

head, the neck and of the upper thorax with a 3 mm spacing and 120 ml of IV 

Iopamiro R○was performed to define clinical target volumes (CTV) and organs 

at risk (OAR). Dose was prescribed at the isodose comprising >95% of PTV, 

defined as CTV+5 mm margin. The aim of inverse planning was to spare 

OAR according to the following constraints: Parotids: >30Gy to < 60 % volume; 

larynx: >50Gy to < 30% volume; spine < 45Gy. Daily dose was 2.2Gy 

to PTV66 and 1.8Gy to PTV54. 30 daily fraction in 6 weeks were given with 

concomitant Cisplatinum (30 mg/square meter/weekly). IMRT was performed 

according to the "step and shoot technique" with 6 MV photons. 7 equally 

spaced fields were employed, with a mean number of 17 segments per field. 

Results: We have considered in this analysis only pts treated before March 

2007 (29 pts). It was always possible to respect dose limits to OAR. All evaluable 

patients have achieved a clinical complete remission (CR). 3 pts died 

for other causes at 1 mos, 1 mos and 1 year respectively, while still in CR. 3 

pts developed local recurrence: 2 pts (T2N2a and T3N2c nasopharynx) 15 

mos after treatment and were reirradiated; they are still alive at 30 and 19 

mos from the end of the first treatment respectively. The other one pt (T2N1 

oropharynx) has presented local recurrence at 5 mos and died for disease 

progression. Two pts presented distant metastases. None of the patients 

presents a hyposcialia of grade > 1. 20 pts have been evaluated with QLQ 

H&N35 score: 4pts have a >95% residual swallowing function, 4pts between 

90% and 95%, 7pts between 80% and 90% (4pts


90% of the prescribed dose (54 Gy in 1.8 Gy daily fractions) was determined. 

The influence of reducing the margin for position uncertainty from 5 to 2 mm 

was investigated. 

Results: The mean dose to the contralateral submandibular gland was reduced 

from 54 Gy to approximately 40 Gy if the dose coverage to the contralateral 

PTV was reduced from 95% to 90% of the prescribed dose. The 

estimated normal tissue complication probability (NTCP) was reduced below 

50%. Reducing the margin from 5 to 2 mm resulted in a decrease in the mean 

dose to the contralateral submandibular gland of approximately 6 Gy. 

Conclusions: Reducing the mean dose to the contralateral submandibular 

gland below 40 Gy is possible with a reasonable dose coverage of the contralateral 

elective PTV. 

844 poster 

STEREOTACTIC IRRADIATION FOR ESTHESONEUROBLASTOMA 

OF THE SINONASAL TRACT 

H. Sato 1 , J. Ebi 1 , A. Yukawa 1 , M. Toshima 1 , F. Shishido 1 

1 FUKUSHIMA MEDICAL UNIVERSITY, Radiology, Fukushima, Japan 

Purpose: To review our experiences about Stereotactic Irradiation (STI) in 

the treatment of Esthesioneuroblastoma (ENB). 

Materials: Five patients with ENB of the sinonasal tract who rejected the surgical 

operation and chemotherapy, or who were inoperable, were treated by 

only STI between 1999 and 2005 at Fukushima Medical University. Two of 

them were treated with stereotactic radiosurgery (SRS), and two with stereotactic 

radiotherapy(SRT) , the one with SRT after conventional radiotherapy. 

Results: A mean follow-up was 47Months (8-95Months), all patients showed 

complete response(CR). Three cases were alive with no local recurrence, 

but two died from gastric cancer at 36 Months after treatment and systemic 

metastasis at 12Months after treatment. In one patient treated with SRS, a 

partial resection of left maxillary sinus cavity was required because of fluid 

collection in this cavity. Histological examination revealed that there weren’t 

any viable tumor cells remaining. In the other case, follow-up MRI revealed 

small brain necrosis near the treatment area, but no treatment was required. 

In three with SRT, there were no major side effects. 

Conclusions: We treated five ENB patients with STI without any complimentary 

treatments. All patients showed CR with no local recurrence. STI is a 

successful treatment approach for local control of ENB in the sinonasal tract 

under appropriate conditions. 

845 poster 

STEREOTACTIC RE-IRRADIATION WITH CYBERKNIFE COMBINED 

TO CETUXIMAB FOR RECURRENT HEAD AND NECK TUMOURS 

E. Lartigau 1 , X. Mirabel 1 , T. Lacornerie 1 , B. Coche-Dequant 1 , J. L. 

Lefebvre 2 , F. Dubus 1 , T. Sarrazin 1 

1 CENTRE OSCAR LAMBRET, Academic Radiation Oncology, Lille, France 

2 CENTRE OSCAR LAMBRET, Lille, France 

Purpose: Hypofractionated robotic stereotactic radiotherapy delivers highly 

conformal treatments in few fractions. Preliminary results on feasibility and 

toxicity in reirradiation of head and neck tumours are reported. 

Materials: Between 14/06/2007 and 10/03/08, 16 patients (10 men & 6 

women) have been treated in a feasibility study for a recurrent head and neck 

tumour at the CyberKnife Nord-Ouest in Lille. All patients had been previously 

irradiated in the stereotactic treatment fields (mean dose : 58 Gy) with 

a mean interval time of 3.7 years between primary tumour and recurrence. 

Mean age was 51 (22 to 66 years). Informed consent was given. Histology 

of the primary tumour was squamous carcinoma. Delivered dose was 36 Gy 

(6 X 6 Gy) in 12 days combined with cetuximab for carcinomas (450 mg/m2 

once, followed by 4 times 250 mg/ m2 weekly) starting one week before and 

ending 2 weeks after the last fraction dose. CTV was GTV + 5 mm margins 

and PTV= CTV. Mean GTV volume was 74 cm3. The prescription isodose 

was the 80 % covering at least 95% of the GTV. Mean fraction treatment time 

was 52 minutes, with a mean of 152 beams per treatment. 

Results: Treatment was well tolerated with only 2 treatment interruptions (5 

days and 1 month). Acute reactions were limited with one patient expresssing 

grade III mucousitis and skin reactions in the treated fields. All patients receiving 

cetuximab expressed grade II to III skin reactions linked to the molecule. 

The protocole is feasible and well tolerated. The first 6 patients (fup > 3 

months) expressed a treatment response (2 complete & 4 partial). 

Conclusions: Cyberknife treatment is feasible and minimally toxic even in 

patients previosusly irradiated for head and neck tumours. Long term local 

control and late toxicity should be evaluated. Hypofractionated robotic 

stereotactic radiotherapy is a new, potentially curative therapeutic option with 

immediate excellent tolerance. A phase II prospective study using this protocol 

is now running. 

846 poster 

SURGERY PLUS HIGH DOSE POST-OPERATIVE RADIOTHERAPY 

YIELDS EXCELLENT LOCAL CONTROL RATE IN PATIENTS WITH 

POSITIVE RESECTION MARGIN FOR MALIGNANT PAROTID 

TUMOURS 

M. Ahmed 1 , S. Bhide 1 , A. Miah 1 , Y. Barbachano 2 , K. Harrington 1 , K. 

Newbold 3 , C. Nutting 1 

1 

ROYAL MARSDEN HOSPITAL, Head and Neck Unit, London, United 

Kingdom 

2 

ROYAL MARSDEN HOSPITAL, Department of Statistics, Sutton, United 

Kingdom 

3 

ROYAL MARSDEN HOSPITAL, Head and Neck Unit, Sutton, United Kingdom 

Purpose: Radiotherapy is commonly used to reduce the risk of recurrence of 

malignant parotid gland tumours. We report our experience with radiotherapy 

for parotid malignancies at the Royal Marsden Hospital. 

Materials: A retrospective review of the case notes of the patients diagnosed 

with malignant parotid tumours treated with megavoltage irradiation, 

from 1995-2005 at the Royal Marsden hospital, formed the basis of this study. 

The following information was obtained: age, sex, details of pathology, type of 

surgery, type of radiotherapy and outcome data. Outcome data included the 

date of recurrence, the type of recurrence i.e. local or metastatic, the date of 

death and the cause of death. This data was used to calculate local control 

rates, disease free and overall survival. 

Results: Forty-five patients (54%) underwent superficial parotidectomy, 

twenty-six (30%) patients underwent total parotidectomy and thirteen patients 

(16%) had fine needle aspiration (FNA). Adenocarcinoma, squamous cell carcinoma 

and mucoepidermoid carcinoma, were the most prevalent histologies. 

Lateral wedged pair field technique was the most frequent method of radiation 

delivery. Fifty-two patients (61%) were treated with one of two radiobiologically 

equivalent dose regimes: 50 Gy in 20 fractions or 60 Gy in 30 fractions. 

This is the standard dose used for sterilising microscopic disease in our institution. 

Twenty-eight patients (33%) were treated with a higher radiation dose 

of 65 Gy in 30 fractions due to the presence of residual macroscopic disease 

(R2 resection). The 5 year locoregional control, disease free and overall survival 

rates, respectively, were 75%, 54% and 58%. Univariate followed by 

multivariate analysis of various factors affecting local recurrence showed age 

(p = 0.02) and T stage (p = 0.02) to be significant. Positive resection margin 

was not associated with worse local control (p=0.4). 

Conclusions: Our study has shown good results in patients receiving post 

operative radiotherapy to the parotid bed, in spite of varied patient mix. In 

addition it demonstrates that patients with positive margins post surgery (R2 

resection) can be salvaged with higher radiation dose. 

847 poster 

THE DOSE TO THE SUPERIOR PHARYNGEAL CONSTRIC- 

TOR DOES NOT AFFECT SUBJECTIVE OR THE OBJECTIVE 

DYSPHAGIA-RELATED PARAMETERS POST CHEMO-IMRT FOR 

HEAD AND NECK CANCER 

S. Bhide 1 , S. Gulliford 2 , R. Kazi 1 , R. Dwivedi 1 , K. Harrington 1 , C. Nutting 

1 

1 ROYAL MARSDEN HOSPITAL, London, United Kingdom 

2 ROYAL MARSDEN HOSPITAL, Academic Physics, Sutton, United Kingdom 

Purpose: It has been postulated that the probability of dysphagia post 

chemo-radiation in head and neck cancer squamous (HNC) increases with 

increasing dose to the pharyngeal constrictors (PC), especially superior constrictor 

(SC) . The aim of this study is to correlate the dose to the PC with 

the subjective and objective assessments of swallowing in patients with HNC 

undergoing IMRT and concomitant chemotherapy. 

Materials: DVHs for SC, middle (MC) and inferior constrictors (IC) were 

generated for 37 patients who had undergone chemo-IMRT (accelerated hypofractionated 

RT equivalent to at least 66 Gy in 33 fractions and cisplatin 

100mg/m2 week 1&5) for locally advanced HNC. The mean radiation dose to 

each constrictor was obtained and converted to equivalent dose in 2 Gy fractions. 

All patients completed the MD Anderson dysphagia inventory (MDADI) 

questionnaire at 1 year post treatment. Objective late dysphagia score was 

documented at 1 year using the RTOG late toxicity criteria. The mean dose to 

each of the constrictors was correlated to the objective dysphagia grade and 

global, total physical (TP) and two most relevant components of the physical 

section of the MDADI (P6:"swallowing takes a great effort" & P8:"I cough 

when I try to drink liquids"), using the Spearman’s rank correlation. The odds 

ratio of dysphagia (>grade 0), poor global (

SC were not significantly higher than patients receiving < 60 Gy. The mean 

dose to the MC was >60 Gy in all patients. 

Conclusions: The radiation dose to any of the Individual constrictors (SC, 

IC & MC) does not correlate to the objective dysphagia grade or the patient 

reported MDADI questionnaire at 1 year, in our study. Future prospective 

assessment of a larger cohort of patients needs to be undertaken prior to 

implementing PC sparing IMRT. Sparing the PC might lead to a geographical 

miss, especially SC keeping in mind its close proximity to the lateral retropharyngeal 

nodes and the parapharyngeal spaces. Table showing the R 2 and 

Odds ratios (mean dose < vs. > 60 Gy) for the PC’s (Note: The mean dose 

to the MC > 60 Gy for all patients therefore odds ratios not generated). 

848 poster 

THE EFFECT OF SMOKING HISTORY ON LOCAL CONTROL IN 

THE PATIENTS WITH EARLY GLOTTIC CANCER TREATED WITH 

RADIOTHERAPY 

L. Özkan 1 , C. Demiroz 1 , U. Gurlek 1 

1 ULUDAG UNIVERSITY MEDICAL FACULTY, Radiation Oncology, Görükle / 

Bursa, Turkey 

Purpose: The aim of this study is to determine the effect of smoking history 

on local control for the patients with early glottic squamous cell carcinoma 

(T1-2N0M0) who were treated with radiotherapy. 

Materials: Between October 1995 and December 2006, 79 patients with 

early glottic squamous cell carcinoma of larynx (T1-2N0M0) who were treated 

at the department of radiation oncology of Uludag University Medical Faculty 

were retrospectively evaluated for the effect of smoking history on local control.Median 

age was 58 and 75 (95%) of them were male. All of the patients 

had been diagnosed the squamous cell carcinoma of glottic larynx, histopatologically. 

Distribution by histologic grade was as follows: grade-1; 52%, 

grade-2; 30%, grade-3; 5% and undetermined 13%. Factors estimated as 

prognostic were age at the diagnosis, histologic grade, clinical stage, anterior 

commissur involvement, and smoking history as number of daily cigarettes 

and period of time as smoker. Five and ten years of local control and survival 

were determined by using life-time tables. Kapplan-Meier log rank test were 

used for univariat analysis while multivariat analysis were made by using Cox 

regression test. 

Results: Median follow up time for the living patients was 62 months. In the 

following period, one of the patients were died from the disease while 15 of 

them were died by other causes. 10 patients had experienced local failure. 

Ten years local control rate was 87,3%. More than 20 cigarettes in a day was 

found as the most important worse prognostic factor on local control in the 

univariat (p= 0,06) and multivariat (p=0,074) analyses. 

Conclusions: More than 20 cigarattes smoking in a day was found as the 

most important negative prognostic factor for the patients with early glottic 

carcinoma. 

849 poster 

THE GRONINGEN RADIOTHERAPY-INDUCED XEROSTOMIA 

QUESTIONNAIRE: DEVELOPMENT AND VALIDATION OF A NEW 

XEROSTOMIA QUESTIONNAIRE FOR PATIENTS TREATED WITH 

RADIOTHERAPY FOR HEAD AND NECK CANCER. 

M. Christianen 1 , F. Burlage 1 , H. Bijl 1 , O. Hoegen-Chouvalova 1 , T. Bock, 

de 2 , H. Langendijk 1 

1 UMCG, Radiotherapy, Groningen, Netherlands 

2 UMCG, Department of Epidemiology, Groningen, Netherlands 

Purpose: Xerostomia is a frequently reported side effect among patients 

treated with radiotherapy for head and neck cancer. Currently, in many studies, 

the EORTC QLQ-H&N35 is being used to assess patient-rated xerostomia. 

However, this questionnaire only contains one question regarding xerostomia 

and does not enable evaluation of different aspects of patient-rated 

xerostomia. In particular, to determine the added value of new radiation techniques, 

such as IMRT, a more comprehensive questionnaire is required to 

assess the different aspects of salivary function. Therefore, we developed 

and validated a new instrument, the Groningen Radiotherapy-induced Xerostomia 

Questionnaire (GRIX). 

Materials: First, a list of questions regarding salivary function was composed 

by literature review and expert opinions. This list of questions was reviewed 

by experts in this field and by patients. Based on this review, the final GRIX 

was established. Eventually, the final GRIX contained 16 questions (e.g. dry 

mouth at rest, during exercise, during speaking, during the night) which can 

also be organized into 2 subscales (xerostomia and sticky saliva). In addition, 

factor analysis was performed and the GRIX was tested on internal consistency, 

stability (test-retest reliability) and responsiveness in 140 subsequent 

head and neck cancer patients treated with curative (chemo-)radiation. Patients 

were asked to fill out the questionnaire at baseline, weekly during RT 

and at 6 weeks and 6 months after completion of RT. 

Results: The factor analysis revealed that the two subscales, xerostomia 

and sticky saliva scored very high regarding internal consistency (cronbachs 

alpha 0.95 and 0.93, respectively). For the stability, we used GRIX from base- 


S 271 

line and the one on the first day of treatment. Patients with oral surgery and 

dental extractions before radiotherapy and patients who were unable to fill in 

the second GRIX on the first day of treatment were left out of this analysis. 

The test-retest reliability was very good. Furthermore, the responsiveness of 

both subscales was high, with significantly higher scores with increasing dose 

to the salivary glands during the course of treatment. Overall, the outcome of 

the questionnaire revealed different patterns of xerostomia and sticky saliva 

among different patients, e.g. differences in xerostomia at rest and during 

exercise. 

Conclusions: The Groningen Radiotherapy-induced Xerostomia Questionnaire 

is a reliable and valid instrument to assess different aspects of radiationinduced 

xerostomia among patients with head and neck cancer and can be 

used to evaluate the efficacy of advanced and emerging radiation delivery 

techniques. 

850 poster 

THE PREDICTIVE VALUE OF CLINICAL AND IMAGING EXAM- 

INATION PRIOR TO NECK DISSECTION AFTER DEFINITIVE 

RADIOTHERAPY FOR LOCOREGIONALLY ADVANCED CANCERS 

OF THE HEAD AND NECK 

M. Garg 1 , P. Ahn 1 , S. Kalnicki 1 , R. Smith 2 , M. Haigentz 3 , R. Owen 4 , B. 

Schiff 2 

1 MMC/AECOM, Radiation Oncology, Bronx, USA 

2 MMC/AECOM, Department of Otolaryngology, Bronx, USA 

3 MMC/AECOM, Medical Oncology, Bronx, USA 

4 MMC/AECOM, Department of Head and Neck, Bronx, USA 

Purpose: In this retrospective analysis, we seek to elucidate factors that can 

identify the utility of planned neck dissection and postradiotherapy imaging 

for advanced cancers of the head and neck area after definitive radiotherapy. 

Materials: Results from 28 patients with N1 (2 patients), N2 (20), or N3 (6) 

neck disease treated from the years 2000 to 2007 who underwent neck dissection 

up to 1 year after completing definitive radiotherapy were retrospectively 

examined. Characteristics of this population included a median age of 

58 years (range: 34-70 years). A chart review was conducted comparing the 

results of physical examination in any available radiation oncologist, ENT or 

medical oncologist’s notes (23 patients), as well as PET-CT (16 patients) and 

CT/MRI scan (16 patients) prior to any neck dissection, with the pathologic 

results of neck dissection and any biopsy or resection of the primary site. 

Patient outcomes data was also examined, with a median follow-up of 16.2 

months (range: 3.1-84.4 months). 

Results: 16/28 patients had residual disease on neck dissection, in a manner 

that was highly dependent on preradiotherapy neck burden. For N3 disease, 

5/6 patients had residual neck disease on dissection. For N2 disease, 7/20 

patients had residual disease in the neck, all but 1 of which were predicted by 

a combination of physical examination, PET-CT and dedicated CT scan. For 

residual disease in the neck, physical examination had a sensitivity of 16.7% 

and specificity of 46.7%, with a positive predictive value (PPV) of 11.1% and 

negative predictive value (NPV) of 58.3%. Pre-dissection PET-CT had sensitivity 

of 66.7% and specificity of 90%, with a PPV of 80% and NPV of 81.8%. 

Dedicated CT or MRI of the neck had sensitivity of 85.7% and specificity of 

60%, with a PPV of 60% and NPV of 85.7%. For primary disease, examination 

had sensitivity of 40% and specificity of 93.8%. PET-CT had sensitivity 

of 75% and specificity of 72.7% for primary disease, while dedicated 

CT or MRI had sensitivity of 100% and specificity of 72.7%. For disease of 

the neck, the patients in whom PET-CT predicted for a true residual or true 

eradication of neck disease had their scan an average of 2.7 months after 

completing radiotherapy, versus 2.3 months for patients with false positive of 

false negative residual disease (p=0.08). Similar trends are true for the interval 

between completion of radiotherapy with physical examination as well 

as pre-dissection CT/MRI. Overall, there is a disease-specific survival rate of 

89.3%. 

Conclusions: In patients with N1+ neck disease, PET-CT prior to neck dissection 

has utility in predicting any residual disease in the primary site and 

the neck. The results of this small, retrospective analysis that it would be a 

reasonable option to observe patients with N2 neck disease for any residual 

disease in the neck, while patients with N3 disease should undergo planned 

neck dissection. Pre-dissection PET-CT may have little utility in patients with 

N3 neck disease due to the preponderance of residual neck disease in this 

population.


851 poster 

THE PRIMARY PREVENTION OF TRISMUS IN PATIENTS UN- 

DERGOING RADIOTHERAPY TO THE MASSETER, TEMPORALIS, 

PTERYGOID MUSCLES AND TEMPOROMANDIBULAR JOINT. 

V. Loorents 1 , K. Hultman 1 

1 DEPARTMENT OF RADIATION ONCOLOGY, Radiotherapy, Linköping, 

Sweden 

Purpose: Background Trismus is a very painful condition, which results 

in a limited mouth opening. This leads to difficulty in eating, swallowing, 

speech and general mouth hygiene. Patients suffering from trismus often 

have chronic pain with depressive tendencies, which has a significant effect 

on their quality of life. Trismus can occur in patients undergoing radiotherapy 

to specific areas of the head or neck. Research in the area of trismus is limited; 

it is not known exactly when trismus develops, one study suggests that 

some patients have experienced a diminished opening at as low doses as 15 

Gy. Literature suggests benefits of a training programme, but there is a lack 

of evidence to support the use of a training programme during radiotherapy. 

Aim To investigate the effectiveness of prophylactic training methods during 

radiotherapy, comparing a training device to physiotherapy in the prevention 

of trismus. The study also aims to investigate the incidence of radiotherapyinduced 

trismus in patients who receive radiotherapy to the masseter, temporalis, 

pterygoid muscles and even the temporomandibular joint. Investigating 

trismus and quality of life during radiotherapy and up to one year after completed 

treatment. Goal The prevention of trismus during radiotherapy. 

Materials: Randomised controlled prospective study Group 1: The TheraBite 

Jaw Motion Rehabilitation System. Group 2: Physiotherapy. Group 3: Traditional 

therapy An oncologist identifies the target area; the respondents are 

randomised into one of the three groups. A hospital specialist dentist measures 

the mouth opening every week, during radiotherapy and during followup 

(up to one year) after radiotherapy. Quality of life is measured during 

radiotherapy and during follow-up (3 months and 6 months) using FACT-H&N 

(version 4). 

Results: Expected results 40% of the respondents will have developed trismus 

during or after radiotherapy. A 40% decrease in incidence of trismus with 

the use of TheraBite Jaw Motion Rehabilitation System A 20% decrease in 

incidence of trismus with physiotherapy. 

Conclusions: 

852 poster 

THE PROGNOSTIC VALUE OF NODAL RATIO (NR) IN LOCALLY AD- 

VANCED OPERABLE SQUAMOUS CELL CARCINOMA OF THE HEAD 

AND NECK (SCCHN): ANALYSIS OF PROSPECTIVE RANDOMIZED 

TRIAL ON POSTOPERATIVE CONCOMITANT CHEMORADIOTHER- 

APY (CRT) WITH MITOMYCIN C AND BLEOMYCIN 

P. Strojan 1 , M. Budihna 1 , B. Zakotnik 2 , L. Smid 3 

1 

INSTITUTE OF ONCOLOGY LJUBLJANA, Department of Radiation Oncology, 

Ljubljana, Slovenia 

2 

INSTITUTE OF ONCOLOGY LJUBLJANA, Department of Medical Oncology, 


3 

UNIVERSITY CLINICAL CENTER, Department of ENT Surgery, Ljubljana, 

Slovenia 

Purpose: To examine the prognostic power of the NR of positive/excised 

nodes in predicting disease-free survival (DFS) of pts with locally advanced 

operable SCCHN treated in prospective randomized trial (‘mid L et al, Int J 

Radiat Oncol Biol Phys 2003;56:1055-62). 

Materials: Data from 55 pts (RT arm) and 59 pts (CRT arm) with stage III/IV 

SCCHN treated between 1997-2001 in prospective randomized trial on post- 

operative concomitant CRT were analyzed. Chemotherapy included Mitomycin 

C 15 mg/m2 IV after 10 Gy and Bleomycin 5 mg IM twice weekly during 

RT. Patients’ and tumor characteristics were well balanced between the two 

arms. Median follow-up was 76 mos (48-103 mos). The whole data set and 

each of the treatment arms separately were statistically evaluated for DFS 

using Cox regression in respect to the established prognostic factors found 

to be significant indicators of patients’ survival in univariate analysis. NR was 

analyzed as continuous variable. DFS was defined as the time interval between 

surgery and locoregional recurrence or systemic dissemination (DFS1) 

or death from any cause (DFS2). 

Results: The median number of excised nodes was 17, range 4-103 (RT: 

17.5, 4-103; CRT: 17, 4-60), and of positive nodes 2, range 0-18 (RT: 2, 

0-14; CRT: 2, 0-18). In multivariate analysis for DFS1, only the presence 

of one or more high-risk prognostic factors (extracapsular extension CE perineural, 

lymphatic, and/or venous invasion and/or residual disease) was retained 

in the final model (p=0.018, RR=2.79, 95% CI=1.19-6.53); other variables 

tested: TNM stage and NR, p>0.05. After stratifying the patients according 

to treatment arm, NR appeared as the only significant variable in RT 

arm (p=0.038, RR=50.7, 95% CI=1.24-2073.67); presence of high-risk prognostic 

factors and tumor site, p>0.05. In CRT arm, none of the variables 

tested reached the level of statistical significance (pN stage, ECE and NR, 

p>0.05). For DFS2, use of chemotherapy (p=0.025, RR=0.52, 95% CI=0.29- 

0.92) tumor site (larynx vs. others: p=0.034, RR=2.37, 95% CI=1.07-5.27) 

and NR (p=0.047, RR=5.51, 95% CI=1.02-29.65) were retained in the final 

model (high-risk prognostic factors and TNM stage, p>0.05). In RT arm, 

NR appeared as the only but marginally significant prognosticator (p=0.056, 

RR=21.90, 95% CI=0.93-517.91); tumor site and presence of high-risk prognostic 

factors, p>0.05). None of the factors tested was significant in CRT arm 

(NR, pN stage, ECE, p>0.05). 

Conclusions: The addition of chemotherapy to postoperative RT compensate 

for the negative impact of adverse prognostic factors, including that of 

NR, on DFS. 

853 poster 

THE USE OF INTENSITY MODULATED RADIATION THERAPY 

(IMRT) IN THE TREATMENT OF NASOPHARYNGEAL CANCER: THE 

REGINA ELENA INSTITUTE EXPERIENCE. 

L. Marucci 1 , G. Giovinazzo 1 , I. Sperduti 2 , L. Strigari 3 , S. Marzi 3 , G. 

Arcangeli 1 

1 REGINA ELENA INSTITUTE, Radiation Oncology, Rome, Italy 

2 REGINA ELENA INSTITUTE, Department of Biostatistics, Rome, Italy 

3 REGINA ELENA INSTITUTE, Medical Physics, Rome, Italy 

Purpose: Nasopharyngeal cancer, in spite of its radiosensitivity, has long 

been a challenge for the radiation oncologist because of its proximity to critical 

normal structures. IMRT offers the possibility of highly conforming the 

dose around the target, while sparing surrounding normal tissues. This is the 

initial report of a prospective study on the use of IMRT in the treatment of 

nasopharyngeal cancer. 

Materials: From January 2003 to August 2007, 48 patients were treated with 

IMRT for non metastatic nasopharyngeal cancer. All patients were immobilized 

with a thermoplastic mask. A CT scan was performed with 3mm slices. 

The GTV (macroscopic disease including the primary and macroscopically involved 

nodes), CTV1 (regions at high risk of microscopic disease) and CTV2 

(regions at intermediate risk of microscopic disease) were contoured on each 

slice. The targets were expanded 5mm to obtain the PTVs. The dose prescribed 

to the PTVGTV was 70Gy, 60Gy to the PTVCTV1, and 54Gy to the 

PTVCTV2, delivered in 33 fractions with the SIB (simultaneous integrated 

boost). Patients with more locally advanced disease also received concomitant 

and adjuvant chemotherapy. 

Results: Mean patients age was 53 years (range 18-84). Histology was 

squamous cell carcinoma G3 in 14 and undifferentiated carcinoma in 34 patients. 

14 patients were classified as stage I or II and 34 stage III or IV. 85% of 

the patients received chemotherapy. Median follow up was 24 months. The 

2 years actuarial local control was 96%. One patient with a cT3 lesion and 

infiltrated carotid died after 3 months of carotid blow out. Another patient with 

a cT2 lesion had a recurrence within the cavernous sinus, outside the target 

volume, after 2 years and was retreated. None of the patients recurred in 

the neck. The actuarial 2 years disease free survival (DFS) and cancer specific 

overall survival were 82.4% and 91.2%, respectively. When calculated 

separately, the 2 years DFS was 100% for patients in stage I-II and 74.2% 

in stage III-IV. Metastasis, as expected, had higher incidence in patients with 

advanced nodal disease (cN2-3). Mean parotid glands dose was 33.4Gy. At 

18 months the incidence of severe xerostomia was 23%. 

Conclusions: The use of IMRT in the treatment of nasopharyngeal cancer 

resulted in high loco-regional control. The decrease in parotid glands mean 

dose resulted in low % of severe xerostomia. Distant metastasis remain the 

dominant problem and warrant the need to find new and more efficacious 

drugs.

854 poster 

THE USE OF MRI IN THE EVALUATION OF RADIATION-INDUCED 

CHANGES IN WATER AND FAT CONTENT OF THE PAROTID GLAND 

N. Raaijmakers 1 , A. Houweling 1 , N. van den Berg 1 , T. Dijkema 1 , J. 

Roesink 1 , C. Terhaard 1 

1 UNIVERSITY MEDICAL CENTER, Radiotherapy, Utrecht, Netherlands 

Purpose: Xerostomia is the most common side effect after radiotherapy (RT) 

in patients with head-and-neck cancer. The underlying effects are still not 

fully understood. The water content of the parotid gland is most likely changing 

due to radiation damage. Various MR methods to study water content are 

available, from which MR sialography and a multi-point Dixon technique were 

applied in this study. With the Dixon technique, it is also possible to investigate 

the fat content, the second main component of the parotid gland after 

water. 

Materials: Five healthy subjects were scanned to determine the natural variation 

in water content in healthy parotid glands. Three patients were included, 

they all received a high dose to one parotid gland and a lower dose to the 

other gland, which resulted in a difference in remaining salivary flow rate between 

both parotid glands.The sagittal oriented images were acquired on a 

3.0 T MR scanner (Achieva, Philips Medical Systems, Best, NL), using lateral 

located FLEX M surface coils. The sialography images were acquired using 

a MS TSE sequence (TR/TE = 6000/190). The multi-point Dixon technique 

was a 2D gradient-echo sequence (TR/TE = 65/9.9) using 4 echoes (delta TE 

= 0.5). 

Results: The sagittal sialography images showed the salivary ductal system 

within the parotid gland. The contour of the gland was clearly visible as an 

area of increased signal intensity (figure A). The sialography images of the 

patients were very similar to the images of the healthy subjects (figure A 

& D) and the signal intensities of the irradiated glands were in the range 

of the natural variation.The sagittal Dixon water and fat images showed a 

homogeneous water and fat content among the parotid gland. The images of 

the patients were again very similar to the images of the healthy subjects. The 

Dixon water signal intensities of the irradiated glands were within the range of 

the natural variation. However, there was a difference in the Dixon fat images 

between the functioning and the damaged gland in patients (figure C & F). 

Conclusions: In this small pilot study, we observed no damage to the large 

ductal system or a change in water content of the parotid gland as a radiationinduced 

effect. It appeared that there was a difference in the fat content after 

a high RT dose, which could account for a difference in tissue composition. 

In order to further determine this effect, more patients will be scanned before 

and at several time points after RT. 


855 poster 

S 273 

TREATMENT OF CARCINOMA OF THE EXTERNAL AUDITORY 

CANAL AND MIDDLE EAR : A SINGLE INSTITUTIONAL RETRO- 

SPECTIVE REVIEW 

H. C. Kang 1 , H. G. Wu 1 , C. I. Park 1 , C. S. Kim 2 , S. H. Oh 2 

1 SEOUL NATIONAL UNIVERSITY COLLEGE OF MEDICINE, Radiation 


2 SEOUL NATIONAL UNIVERSITY COLLEGE OF MEDICINE, Department of 

Otolaryngology, Seoul , Korea Republic of 

Purpose: To investigate the roles of radiotherapy in treating patients with 

carcinomas of the external auditory canal and middle ear. 

Materials: A series of 51 patients with histologically confirmed carcinoma 

who were treated between 1981 and 2007 in our institutions were analyzed. 

Thirty-nine patients with squamous cell carcinoma (SqCC) and 12 patients 

with non-squamous cell carcinoma (nine with adenoid cystic carcinoma, 2 

with sebaceous carcinoma, 1 with basal cell carcinoma) were treated. The 

patients treated by radiotherapy alone received 39-70 Gy (median 66 Gy) in 

13-35 fractions. The patients treated with perioperative radiotherapy received 

44-70 Gy (median 61.2 Gy) in 22-37 fractions. Clinical end-points were overall 

survival, disease-free survival (DFS) and analyzed only for patients with 

SqCC. The median follow-up was 1.7 years (range: 0.2-18.5 years). 

Results: The 5-year overall survival rate calculated by the Kaplan-Meier 

method for patients with SqCC was 81%. On multivariate analysis, performance 

status (ECOG-ps), T-stage (Stell’s stage) and disease free status had 

significant impact on overall survival. The 5-year DFS rate was 64%. Treatment 

modality was significant factor in DFS on multivariate analysis. Patients 

treated by radiotherapy alone had lower 5-year DFS rate (38%) compared 

with the others’ (79%) (p = 0.034). In surgery alone group, all patients had T1 

disease and been controlled until last follow up. 

Conclusions: For advanced (T2-3) SqCC of the external auditory canal and 

middle ear, surgery with radiotherapy is the preferred treatment. 

856 poster 

TREATMENT OF OROPHARYNGEAL CARCINOMA WITH HY- 

POFRACTIONATED RADIOTHERAPY 

A. Choudhury 1 , D. Williamson 1 , J. Anderson 1 , C. Coyle 1 , K. Dyker 1 , M. 

Sen 1 

1 ST JAMES’S INSTITUTE OF ONCOLOGY, Clinical Oncology, Leeds, United 

Kingdom 

Purpose: Oropharyngeal squamous cell carcinoma has been treated with 

accelerated hypofractionated radiotherapy in order to improve local control, 

although this may be at the expense of increased early and late toxicity. We 

have audited the toxicity and two year disease-free survival in patients treated 

at the regional centre in Leeds. 

Materials: Between 2004 and 2005, patients with oropharyngeal cancer were 

treated with a hypofractionated radiotherapy regime: 55 Gy/20# to the primary 

tumour site and 40 Gy/15# to the uninvolved regional lymph nodes. The use 

of induction and concurrent chemotherapy was noted. Both early and late 

toxicity were assessed. Disease-free survival at two years was documented 

Results: Twenty-eight patients were treated between August 2004 and 

September 2005. The median age at diagnosis was 59 years (Range: 35-85 

years). All patients had stage II-IV disease and were of good performance 

status (WHO 0 to 1). Thirteen patients had induction chemotherapy and 

nine patients had concurrent chemoradiotherapy with platinum. Fifteen patients 

required admission for management of acute toxicity. Median follow 

up was 25 months (Range: 7-41 months). Two of the patients had significant 

late toxicity (grade 3 or 4) and still required enteric feeding when last 

assessed. Disease-free survival was higher in those patients treated with 

concurrent chemoradiotherapy compared to those treated with radiotherapy 

alone (100% v 82% at 2 years, logrank p=0.15), although there was no difference 

in disease-free survival in patients treated with or without induction 

chemotherapy (92% v 85%, logrank p=0.93). Late toxicity was acceptable. 

Conclusions: Hypofractionated radiotherapy regimes can be used to treat 

oropharyngeal squamous cell carcinoma, although early toxicity needs to be 

managed as an inpatient in the majority of patients. Late toxicity is acceptable. 

The addition of concurrent platinum chemotherapy results in increased 

disease-free survival in carefully selected patients. 

857 poster 

TREATMENT OUTCOMES FOR OROPHARYNGEAL SQUAMOUS 

CARCINOMA PRESENTING WITH N3 DISEASE 

S. Iganej 1 

1 KAISER PERMANENTE, Radiation Oncology, Los Angeles, USA 

Purpose: Patients with advanced neck disease have traditionally been 

thought to have poor prognosis and, therefore, aggressive treatment is controversial. 

The purpose of this study was to retrospectively evaluate outcomes

S 274 CLINICAL/DISEASE SITES : LUNG 

for patients with oropharyngeal squamous cell carcinoma presenting with N3 

nodal disease, who had undergone potentially curative therapy. 

Materials: From January 1995 through October of 2003, 27 patients with 

N3 oropharyngeal cancer were treated definitively (median follow-up, 34.5 

months) at our institution. Thirteen patients were treated with concurrent 

chemoradiotherapy, 6 had initial surgery followed by adjuvant RT, 6 underwent 

radiotherapy (RT) alone and 2 patients had induction chemotherapy followed 

by RT. 

Results: With a median follow-up of 71 months for surviving patients, 13 patients 

(48%) had recurrent disease. Local, Regional and Distant recurrences 

were noted in 22%, 26%, and 30% of patients, respectively. Median time to 

failure was 9 months. Locoregional control was achieved in 84% of patients 

who were treated with either surgery followed by adjuvant RT, or concurrent 

chemoradiation with the remaining patients having only a 25% rate of locoregional 

control, P=0.01. At last follow-up, 13 (48%) patients were alive with 

no evidence of disease, another had died of intercurrent disease, and the 

remaining 13 had died of disease. 

Conclusions: This review suggests that a considerable portion of patients 

with oropharyngeal squamous cell carcinoma who present with N3 disease 

will have long-term survival without any recurrence when treated aggressively, 

with either concurrent chemoradiation or surgery followed by adjuvant 

therapy. 

858 poster 

TREATMENT RESULTS AND PROGNOSTIC FACTORS OF NA- 

SOPHARYNGEAL CARCINOMA: A SINGLE INSTITUTION’S 

EXPERIENCE 

M. G. Aksu 1 , A. F. Korcum 1 , M. Ozdogan 2 , D. Ural 1 

1 AKDENIZUNIVERSITY, Radiation Oncology, Antalya, Turkey 

2 AKDENIZUNIVERSITY, Medical Oncology, Antalya, Turkey 

Purpose: Treatment results and prognostic factors in patients with locoregionally 

advanced nasopharyngeal carcinoma treated with concurrent 

chemoradiotherapy were analyzed. 

Materials: A total of 55 patients with histologically proven and non metastatic 

nasopharyngeal carcinoma that were treated between 2000 and 2007 were 

evaluated retrospectively. There were 37 males and 18 females, their ages 

ranging from 19 to 74 years (median, 50 years). Tumor stage was I in one 

patient, II in six, III in 29 and IV in 19 patients. Conventional external radiotherapy 

with a total dose of 60-72 Gy (1.8-2 Gy/fraction) was delivered to 

all patients. An intracavitary brachytherapy boost of 6-10 Gy was delivered 

to 7 patients. Five patients treated with radiotherapy alone and 50 patients 

received concurrent cisplatin based chemotherapy. Neoadjuvant chemotherapy 

which consisted of docetaxel+cisplatin± 5-fluorouracil was delivered in 8 

(14,5%) patients while 16 (29.1%) patients received radiotherapy followed by 

adjuvant chemotherapy which consisted of cisplatin and 5-fluorouracil. Univariate 

and multivariate analyses were performed to identify variables significantly 

associated with disease-free survival, and overall survival. 

Results: The most frequent grade 3+ acute radiation side effects were 

esophagitis (12.7%), mucositis (10.7%) neutropenia (8.6%) and dermatitis 

(3.6%) while late effects were xerostomia (1.8%), esophagitis (3.5%) and mucositis 

(1.8%). Most of the patients lost median 11% of pretreatment weight 

during radiotherapy. Median follow-up was 19,4 (4.5-93) months. Complete 

response was seen in 76.4% of patients. Local failure was observed in six 

patients and distant metastasis in 13 patients. Median disease-free and overall 

survivals were 42,9 and 67 months, respectively. Three years disease-free 

and overall survival rates were 51% and 54,9%, respectively. Complete tumor 

response after radiotherapy has statistically significant effect on both diseasefree 

and overall survival (p

861 poster 

A COMPARISON OF DIFFERENT QUANTITATIVE SPECT RE- 

CONSTRUCTION TECHNIQUES: 3D PERFUSION MAPS, AND 

CALCULATIONS OF FUNCTION-WEIGHTED DOSE IN LUNG 

A. Thompson 1 , A. Celler 2 , J. Powe 3 , D. Worsley 3 , S. Shcherbinin 2 , L. 

Yin 4 , C. Duzenli 4 , V. Moiseenko 4 , B. Gill 4 , F. Sheehan 1 , C. Marlowe 5 

1 

VANCOUVER CANCER CENTRE, BRITISH COLUMBIA CANCER AGENCY, 

Radiation Oncology, Vancouver, Canada 

2 

UNIVERSITY OF BRITISH COLUMBIA, Radiology, Vancouver BC, Canada 

3 

VANCOUVER GENERAL HOSPITAL, Nuclear Medicine, Vancouver, Canada 

4 


Medical Physics, Vancouver, Canada 

5 


Radiation Therapy, Vancouver, Canada 

Purpose: Single Photon Emission Computerized Tomography (SPECT) provides 

a means of creating three-dimensional (3D) maps of lung perfusion. 

Such information can potentially be used in planning function-sparing radiation 

therapy. However, the effects of SPECT image reconstruction remain 

undetermined. In this study we investigated the impact of different quantitative 

SPECT reconstruction techniques on 3D perfusion maps, and calculated 

functional burden-weighted doses (FWD) for lung cancer patients. 

Materials: Patients with a diagnosis of lung cancer, and prescription dose ≥ 

30Gy were prospectively recruited. Following their planning CT-scan, patients 

had a SPECT-CT scan where they were set up in the treatment position. Intravenous 

technetium-99m labeled macro-aggregated albumin was injected 

prior to the scan. Four SPECT reconstruction techniques were studied: (i) 

neither attenuation nor scatter was used (NCF); (ii) the CT-based attenuation 

map was scaled to indirectly account for scatter (BBF); (iii) full CT-based 

attenuation and scatter corrections (NBF); and (iv) the vendor’s reconstruction 

(CAM). The SPECT-CT images were registered to the planning CT, and 

the normal lung volume was defined as whole lung minus gross tumour volume. 

Two definitions of functional lung were explored. First, cut-off levels of 

SPECT signal were determined so that 10, 20,& 90% of normal lung voxels 

had SPECT signal values above these levels. For example, V30 would mean 

the top 30% of normal lung as ranked by SPECT signal. Second, volume 

cut-off levels were determined in order to rank normal lung voxels according 

to cumulative SPECT signal. FWD values were calculated for these lung 

volumes. 

Results: Substantial spread of FWD was demonstrated for the different 

SPECT reconstruction techniques. The difference was particularly pronounced 

for the 10-50% of lung showing SPECT signal above the cut-off. 

For a representative patient planned to receive 60 Gy to isocentre, FWD for 

the 10% of lung with the strongest SPECT signal was 3.5 Gy for NCF and 6.2 

Gy for NBF. For the highest 50% volume, corresponding values were 6.9 and 

7.6 Gy. The Figure shows the calculated FWD for a representative patient. 

Differences of a similar order of magnitude were observed for the definition of 

lung volume using volume cut-off levels. 

Conclusions: The method of SPECT reconstruction does affect calculated 

FWD. The use of the more-advanced SPECT reconstruction methods should 

be explored for function-sparing radiation therapy planning. 

862 poster 

A PHASE I STUDY OF PALLIATIVE THORACIC RADIATION WITH 

CONCURRENT AND ADJUVANT NIMOTUZUMAB FOR PATIENTS 

CLINICAL/DISEASE SITES : LUNG 

S 275 

WITH STAGE IIB/III/IV NON-SMALL CELL LUNG CANCER 

A. Brade 1 , G. Bebb 2 , C. Smith 3 , S. Rorke 4 , I. Sherman 5 

1 

PRINCESS MARGARET HOSPITAL - UNVERSITY HEALTH NETWORK, 

Radiation Oncology, Toronto, Canada 

2 

TOM BAKER CANCER CENTRE, Medical Oncology, Calgary, Canada 

3 

HUNTER NEW ENGLAND HEALTH, Area Cancer Services, New South 

Wales, Australia 

4 

H. MICHAEL BLISS CANCER CENTRE, Medical Oncology, St. John’s, 

Canada 

5 

YM BIOSCIENCES, Mississauga, Canada 

Purpose: The epidermal growth factor receptor (EGFR) has been implicated 

in pre-clinical models of non small cell lung cancer (NSCLC) as contributing 

to angiogenesis, metastasis, and resistance to radiation and chemotherapy, 

while its over expression is associated with poorer outcome. Nimotuzumab 

is a humanized monoclonal antibody (mAb) directed against the extracellular 

domain of human EGFR1 that does not exhibit the typical skin and GI toxicity 

seen with other agents in this class. Nimotuzumab administered concurrently 

with radiotherapy is a well-tolerated combination that may enhance radiocurability 

of unresectable head and neck neoplasms. Here we outline the results 

of a phase I trial of this agent given concurrently with and adjuvantly following 

palliative radiation in patients with NSCLC. 

Materials: From March 2005 to December 2007, eligible patients (age >18 

years; histologically or cytologically confirmed Stage IIB, III or IV NSCLC; 

unsuitable for radical radiation or chemo-radiation; measurable disease within 

the planned radiation field) received nimotuzumab as a 30 minute IV infusion 

weekly on weeks 1 - 8 starting on day 1, 2 to 6 hrs after radiation (30 Gy 10 

fractions, Monday to Friday,). If response or disease stability was observed, 

nimotuzumab was continued every other week starting from week 10 until 

progression or toxicity. 

Results: 18 patients (age 46 86; median age 69) have been enrolled in the 

3 cohorts (100/200/400 mg) of the study. ECOG performance status: 0/1/2 

3/10/5. Stages at diagnosis: IIIA/IIIB/IV - 2/6/10. The median number of drug 

infusions was 11 (range 2-23). In 18 evaluable patients, the best observed 

local response was CR/PR/SD/PD - 0/8/8/2. 8 of 18 patients have died and 

3 remain on study therapy. Median overall survival for the first two cohorts is 

40.5 wks. No dose limiting toxicities have been observed and two SAEs have 

been reported as possibly attributable to study therapy Gr 3 pneumonitis and 

Gr 3 neutropenia. 

Conclusions: Nimotuzumab administered concurrently with and adjuvantly 

following palliative radiation is well tolerated up to 400 mg in NSCLC patients 

not fit for chemotherapy. Although it specifically targets the EGF receptor, 

the absence of rash, hypomagnesemia and diarrhea makes it therapeutically 

attractive. A similar study has been recently completed in Korea and preliminary 

data is congruent with the results of this trial. Enrollment on this trial is 

now complete and updated results will be presented at the congress. 

863 poster 

A PRELIMINARY REPORT OF SINGLE FRACTION CARBON-ION 

RADIOTHERAPY FOR STAGE I NON-SMALL CELL LUNG CANCER 

M. Baba 1 , T. Sugane 1 , M. Nakajima 1 , N. Yamamoto 1 , T. A. Miyamoto 2 , 

S. Kandatsu 1 , K. Yoshikawa 1 , N. Matsufuji 2 , S. I. Minohara 2 , T. Kamada 

1 , J. E. Mizoe 1 , H. Tsujii 2 , N. Working Group for Lung Cancer 2 

1 NATIONAL INSTITUTE OF RADIOLOGICAL SCIENCES, Research Center 

Hospital for Charged Particle Therapy, Chiba-shi, Japan 

2 NATIONAL INSTITUTE OF RADIOLOGICAL SCIENCES, Research Center for 

Charged Particle Therapy, Chiba-shi, Japan 

Purpose: We have previously reported successful local control and minimal 

adverse reactions after carbon-ion radiotherapy (C-Ion RT) using 4 or 9 fractionated 

irradiation in stage I non-small cell lung cancer (NSCLC). In this paper 

we describe preliminary the local control and the adverse reactions after 

single fraction C-Ion RT for stage I NSCLC. 

Materials: From April 2003 to August 2007, a total of 72 patients with stage 

I NSCLC were treated in dose escalation study using single fraction C-ion 

RT at Research Center Hospital for Charged Particle Therapy, National Institute 

of Radiological Sciences. Those patients who had a follow-up time 

of 6 months or more were analyzed. The total dose in a single fraction irradiation 

was started at 36.0GyE and escalated by 5% increment: 36.0GyE 

(n=18), 38.0GyE (n=14), 40.0GyE (n=15), 42.0GyE (n=15), 44.0GyE (n=10). 

An average age was 75 years, and gender breakdown was 23 females and 

49 males. The tumors consisted of 47 for T1 and 25 for T2. The average 

tumor size was 27.7 mm in diameter. Histology was all determined by biopsy: 

45 adenocarcinomas, 26 squamous cell carcinomas, and one large cell carcinoma. 

The 65% of the patients had medically inoperable tumors. The targets 

were most commonly irradiated from four oblique directions using respiratorygating. 

Toxicities of CIRT to the skin and lung were assessed according to 

NCI-CTC (early) and RTOG/EOTRC (late). 

Results: All patients were followed up until death, with a median follow-up 

time of 16.1 months, ranging from 1.6 months to 21.6 months. The local 

control rate for the 72 primary lesions was 89.3%, and those for the T1 (n=47) 

and T2 (n=25) tumors were 94.6% and 78.7%. The 28-month overall survival 

rate was 85.4% and the cause-specific survival rate was 98.0%. Early skin


reactions were assessed for 72 lesions and late skin reactions for 69 lesions. 

Of the early reactions, 69 were grade 1 and one was grade 2. Among the late 

reactions, 65 were grade 1, one was grade 2. Lung reactions were clinically 

assessed in the 72 patients. Forty-five had grade 0, and 27 had grade 1 in 

early reaction. Late reactions were scored in 69 patients, and there were 12 

patients for grade 0 and 57 patients for grade 1. 

Conclusions: It is preliminary concluded that C-Ion RT using single fraction 

is promising curative modality for stage I NSCLC. 

864 poster 

A PROSPECTIVE ASSESSMENT OF PULMONARY TOXICITY AFTER 

RADICAL RADIOTHERAPY (RRT) IN PATIENTS WITH POOR LUNG 

FUNCTION 

A. Price 1 , C. Faivre-Finn 2 , M. Snee 3 , S. Erridge 1 , N. Mohammed 4 , S. 

Russell 5 

1 

WESTERN GENERAL HOSPITAL, Oncology, Edinburgh, United Kingdom 

2 

CHRISTIE HOSPITAL, Clinical Oncology, Altrincham, United Kingdom 

3 

COOKRIDGE HOSPITAL, Clinical Oncology, Leeds, United Kingdom 

4 

BEATSON ONCOLOGY CENTRE, Clinical Oncology, Glasgow, United 

Kingdom 

5 

CACTUS, Edinburgh, United Kingdom 

Purpose: Background RRT is the treatment of choice in patients with medically 

inoperable non-small cell lung cancer, but its tolerance in individuals with 

poor lung function is unclear. We report the pulmonary toxicity and physiological 

changes observed in a group of such patients in the year after RRT. Aim 

To determine whether pulmonary radiotherapy toxicity is increased in patients 

with poor lung function, defined as either lung volumes or gas transfer less 

than half predicted. 

Materials: A randomised trial of 55 Gy in 20 fractions over 4 weeks with 

or without weekly low dose gemcitabine was carried out from 2003-5. Lung 

volumes and gas transfer were measured at baseline, 3 and 12 months, and 

CTC v 2.0 toxicity documented at 0, 1, 2, 3 , 6, 9 & 12 months. 

Results: 107 patients were randomised, with baseline lung function data 

available on 102. 35 (34%) had poor lung function with either FEV1 or gas 

transfer 6 weeks (n=1), > 3 months (n=17) or > 6 months (n=1) after RT. 

Definitions of the MTD and Dose Limiting Toxicity were reported in 21 (88%) 

and 19 (79%) of the trials, respectively. MTD was related to late complications 

with a follow-up of more than 3 months, 6 months and 12 months, in 6 

(25%), 1 (4%) and 0 (0%) trials, respectively. Only 3 (13%) trials included a 

detailed power calculation. 

Conclusions: There is no consensus on the methodology used for phase I 

radiation dose escalation trials. Only 7 (29%) of the trials used late toxicity 

data to proceed to the next dose escalation level or to define MTD. These 

results stimulated us to develop guidelines for the design of phase I dose 

escalation trials with RT. To do so we will try to reach consensus among 

experts with the use of a Delphi technique. 

866 poster 

ASSESSMENT OF 2 NOVEL RESPIRATORY SIGNALS FOR USE 

IN THE DELIVERY OF GATED / TRACKED RADIOTHERAPY FOR 

NON-SMALL CELL LUNG CANCER 

S. Hughes 1 , J. McClelland 2 , S. Tarte 2 , S. Ahmad 3 , D. Hawkes 2 , D. 

Landau 3 

1 

KING’S COLLEGE LONDON, Division of Imaging Sciences, London, United 

Kingdom 

2 

UNIVERSITY COLLEGE LONDON, Center for Medical Image Computing, 


3 

GUY’S AND ST.THOMAS’ HOSPITAL NHS FOUNDATION TRUST, Oncology 

Dpt., London, United Kingdom 

Purpose: In selected patients with NSCLC the therapeutic index of radical 

radiotherapy can be improved with gating / tracking technology. Both techniques 

require real-time information on target location. This is often derived 

from a surrogate respiratory signal. We assessed the correlation of 2 novel 

surrogate respiratory signals with a spirometer-derived signal (gold standard). 

The novel signals were obtained using the VisionRT stereoscopic camera 

system. The VisionRT-Tracked-Point (VRT-TP) signal was derived from tracking 

a point located midway between the umbilicus and xiphisternum. The 

VisionRT-Surface-Derived-Volume (VRT-SDV) signal was derived from 3-D 

body-surface imaging of the torso. Both have potential advantages over current 

surrogate signals. 

Materials: 11 subjects with NSCLC were recruited. Each was positioned 

as for radiotherapy treatment, and then instructed to breathe in 5 different 

modes: normal, abdominal, thoracic, deep and shallow breathing. Synchronous 

respiratory signals were recorded for later analysis. The signals 

were analysed for correlation across all modes of breathing, and phase shifts. 

The VRT-SDV was also assessed for its ability to determine the mode of 

breathing. 

Results: Both novel respiratory signals showed good correlation (>0.80) with 

spirometry in 9 out of 11 subjects. For all subjects the correlation with spirometry 

was better for the VRT-SDV signal than the VRT-TP signal. Only one 

subject displayed a phase shift between the VisionRT derived signals and 

spirometry. The VRT-SDV signal could also differentiate between different 

modes of breathing. Unlike the spirometer-derived signal, neither VisionRTderived 

signal was subject to drift.

Conclusions: Both the VRT-TP and VRT-SDV signals have potential applications 

in respiratory-gated and tracked radiotherapy. They can also be used 

as a signal for sorting 4DCT images, and to drive 4DCT single and multipleparameter 

motion models. 

867 poster 

CHANGES OF TREATMENT OUTCOME OF STAGE III NON-SMALL 

CELL LUNG CANCER TREATED WITH CONCURRENT CHEMORA- 

DIOTHERAPY IN THE SINGLE INSTITUTION 

Y. Hamamoto 1 , M. Kataoka 1 

1 SHIKOKU CANCER CENTER, Radiology, Matsuyama, Japan 

Purpose: Concurrent chemoradiotherapy (CCRT) for non-small cell lung cancer 

(NSCLC) was introduced to our institution in 1992. After that, experience 

of chemoradiotherapy increased, diagnostic radiology and chemotherapy 

drugs advanced, and CT simulator was introduced. We investigated 

changes of treatment outcome of stage III NSCLC treated with CCRT between 

1992 and 2005 in our institution. 

Materials: Between 1992 and 2005, 109 patients with stage III NSCLC (stage 

IIIA, 41; stage IIIB, 68) were treated with CCRT in our institution. In the 

early period (1992-1997), the typical treatment was hyperfractionated radiation 

therapy (mean total dose 70.6 Gy) combined with concurrent chemotherapy 

of cisplatin plus 5FU (n=25). In the middle period (1998-2002), the typical 

treatment was conventional radiation therapy of 60 Gy and cisplatin plus docetaxel 

(n=45). In the late period (2003-2005), typical treatment regimen was 

not changed significantly from the middle period (n=39). Median follow-up 

time was 25 months. 

Results: The 3-year overall survival rates were 36% for the early period, 

34% for the middle period, and 45% for the late period (p=0.545). The 3-year 

disease-free survival rates were 28% for the early period, 24% for the middle 

period, and 21% for the late period (p=0.611). The 3-year loco-regional control 

rates were 54% for the early period, 41% for the middle period, and 34% 

for the late period (p=0.789). Treatment-related death occurred in 8% (2/25) 

of patients in the early period, and 4% (2/45) of patients in the middle period. 

No treatment-related death occurred in patients of the late period (0/39). 

Conclusions: Despite increased experience of CCRT and advance of devices, 

survival rates and loco-regional control rates of stage III NSCLC treated 

with CCRT did not improve significantly over 14 years in our institution. 

Treatment-related death decreased in more recent years. 

868 poster 

CISPLATIN/ETOPOSIDE CHEMOTHERAPY COMBINED WITH 

TWICE DAILY THORACIC RADIOTHERAPY FOR LIMITED SMALL- 

CELL LUNG CANCER. RESULTS AND EVALUATION OF ACUTE 

TOXICITY 

J. Lopez Guerra 1 , N. Rodríguez 1 , X. Sanz 1 , P. Foro 1 , A. Reig 1 , J. 

Lozano 1 , I. Membrive 1 , M. Lacruz 2 , J. Quera 2 , E. Fernández-Velilla 1 , M. 


S 277 

Algara 2 

1 HOSPITAL DE LA ESPERANZA, Radiation Oncology, Barcelona, Spain 

2 HOSPITAL DE LA ESPERANZA, UNIVERSIDAD POMPEU FABRA, Radiation 

Oncology, Barcelona, Spain 

Purpose: Schedules of concurrent chemo-radiation in the treatment of small 

cell lung carcinoma are leading to improved survival when compared to sequential 

treatments but also with a considerable increase in acute toxicities. 

We analyze the acute toxicity and the efficacy of concurrent chemotherapy 

and radiotherapy in the treatment of limited stage of small cell lung carcinoma. 

Twice-daily accelerated thoracic radiotherapy has potential advantages over 

once-daily radiotherapy. 

Materials: Since 1999 to 2007, forty patients affected of limited small cell 

lung carcinoma were included. The median age was 61.3 years (range 38 to 

77). Eastern Cooperative Oncology Group (ECOG) performance status was 

≤2. The chemotherapy administrated was Cisplatin (80 mg/m2) on day 1 and 

Etoposide (100 mg/m2) on days 1-3 for four cycles in 70 % of patients, and 

in 95 % of cases the radiotherapy began between the first to third cycles of 

chemotherapy. All patients received a total of 45 Gy of concurrent thoracic 

radiotherapy, given twice daily in 1.5 Gy fractions separated 6 hours each 

other over a three-week period plus a boost of 9 Gy to the tumor. The 80 % 

of patients had profilactic cranial irradiation. This treatment consisted of 10 

doses of 3.0 Gy to the midplane of the brain over a two-week period, for a 

total of 30 Gy in 94 % of cases. 

Results: The most common toxicity was esophagitis (37.5% grade III), followed 

by dermitis. The mean duration of esophagitis was 35 days. Acute 

grade-2 pneumonitis was presented in 7.5% of the patients. In any case the 

radiochemotherapy was interrupted. A complete response was observed in 

27.5 % of cases, a partial response in 57.5 %, stable disease in 5 % and 

7.5 % had local progression. Follow-up ranged from 3.4 months to 8 years 

(median, 23 months). The mediam survival was 23.4 months. The overall survival, 

cause specific survival and local recurrence free survival at two years 

was 47%, 28% and 64.2% respectively 

Conclusions: Radiochemotherapy improve the results in patients with SCLC, 

despite an increased toxicity. The acute side effects seem acceptable and 

controlled with standard treatments. Turrisi et al. reported a 2-year OS rate 

of 47% and cause specific survival rate of 29% for patients receiving twice 

daily fractionation. Despite of the limited number of patients and the shorter 

follow-up these data are promising, because they represent as in published 

data an improve in the response rates, overall survival, cause specific survival 

and local recurrence free survival. 

869 poster 

CLINICAL RESPONSE AND TOXICITY OF THE TREATMENT WITH 

PULMONARY HIGH DOSE RATE BRACHYTHERAPY. 

P. M. Samper Ots 1 , M. C. Lopez Carrizosa 2 , A. Rodriguez Perez 2 , J. 

Escobar 3 , J. M. Delgado Perez 2 , C. Perez Vara 2 

1 

HOSPITAL CENTRAL DE LA DEFENSA "GÓMEZ ULLA", Oncologia Radioterapica, 

Madrid, Spain 

2 

HOSPITAL CENTRAL DE LA DEFENSA, Oncologia Radioterapica, MADRID, 

Spain 

3 

HOSPITAL CENTRAL DE LA DEFENSA, Neumoloía, MADRID, Spain 

Purpose: To analyze the clinical response and toxicity of the treatment with 

endoluminal high dose rate Brachytherapy (BT) in patients with primary or 

metastatic endobronchyal expression. 

Materials: Retrospective study of 119 patients dealt with BT, from January 

of 1992 to December of 2006. Our protocol of BT consists of 4 applications, 

once to the week of 500 cGy, specified to 0.7 cm of the aplicator. System of 

after load, MicroselectrR, plato planning v 3.4.0. The bronchyal tumor was 

primary in 113 cases (95%) and 6 metastatic. 70 patients (58.8%) received 

BT being part of the radical treatment and 49 (41.2%) single with palliative 

intention. 16 patients (13.4%) received concomitant chemotherapy to the BT. 

Control bronchoscopy was performed a month after treatment to evaluate 

the responser to the BT. We have analyzed the clinical response and the 

acute and delayed complications. The statistical analysis has been made 

with SPSS version12.0. 

Results: Age 62.9 + 11.1 years (34-85), 110 patients (92.4%) men. 72 

patients (60.5%) presented previous symptoms to the BT: hemoptysis in 

28 cases (23.5%) and related obstruction in 44 cases (37%). After BT 

68.05% improved, 8.4% presented stabilization, 5.5% clinical progression 

and 18.05% do not consist. Control bronchoscopy showed: 43.7% CR, 34.5% 

PR, 9,2% stabilization, 6.7% progression and 5,9% could not be evaluated. 

8 patients (6.7%) presented acute complications: hemoptysis in 3 cases 

(2.5%), cardiac arrhythmias in 3 cases (2.5%), 1 case bronchoesophageal 

fistula (0.8%) and another patient hematemesis (0.8%). 4 patients (3.3%) 

presented delayed complications: 3 bronchoesophageal fistulas (2.5%) and 

one esophageal stricture (0.8%). From the diagnosis of the primary tumor 

the global average survival and the free survival of disease were 52.12 + 

8.17 months and 36.36 + 4.68 months, respectively. From the BT treatment 

the global average survival and the free survival of disease were 22.99 + 2.65 

months and 16.53 + 1.9 months, respectively. 

Conclusions: The pulmonary BT is well tolerated treatment that obtains im-


provement of the symptoms in 68% of the cases, CR in 43.7%, with a low 

incidence of acute (6,7%) and delayed (3.3%) toxicity. 

870 poster 

COMPARISON OF INTENSITY-MODULATED RADIOTHERAPY 

(IMRT) AND 3D-CONFORMAL RADIOTHERAPY (3D-CRT) FOR THE 

RADICAL TREATMENT OF PANCOAST TUMOURS. 

A. Hollingdale 1 , H. Chantler 2 , S. Harden 1 


2 ADDENBROOKE’S HOSPITAL, Medical Physics, Cambridge, United Kingdom 

Purpose: Pancoast tumours were first described in 1932 as superior sulcus 

tumours characterised by pain, Horner’s syndrome, bony destruction and 

hand muscle atrophy. A variety of tumours can cause this at the superior 

thoracic inlet, and now a pragmatic definition is of an apical primary nonsmall-cell 

lung carcinoma with associated shoulder or arm pain. Due to the 

proximity of the spinal cord to the tumour it has been difficult to treat these 

with high doses of radiotherapy using conventional methods. Here we present 

the use of IMRT as a possible solution. 

Materials: A patient with an inoperable left Pancoast tumour suitable for radical 

radiotherapy was immobilised with a thermoplastic shell from vertex to 

shoulders, and a CT scan performed without intravenous contrast with 3mm 

slices. The following structures were contoured using ARPS (Addenbrooke’s 

Radiotherapy Planning System) in-house software: GTV, spinal canal, lungs, 

oesophagus, and thyroid. Spinal cord PRV was defined as spinal canal 

+ 3mm radially, and GTV-PTV margin was 15mm in all directions, grown 

to avoid cord PRV. The patient was then planned using standard 3D-CRT 

(ARPS; Bentley Milan algorithm) and IMRT (XiO; superposition algorithm) to 

receive 55Gy in 20 fractions, with a maximum cord dose of 80%. A clinical 

comparison of the plans was then performed. 

Results: The 3D-CRT plan used 3 fields with 6MV photons and left anterior 

oblique, right anterior oblique and left posterior oblique fields. The IMRT plan 

was a 5 field step-and-shoot plan with 78 segments evenly distributed. Calculation 

using the Bentley Milan algorithm was slightly inferior compared to 

the superposition algorithm, due to inhomogeneity of dose distribution particularly 

at the lung interface. The IMRT plan allowed wrapping of the high 

dose volume around the spinal cord so that PTV coverage improved without 

significantly increasing the dose to the spinal cord. Comparisons of the doses 

received in each plan are shown in the table below. 

Conclusions: The use of IMRT is superior to standard 3D-CRT in the treatment 

of apical lung tumours allowing increased dose to be delivered without 

compromising normal structures, in particular by shaping the high dose region 

around the spinal cord. Patient immobilisation and good quality assurance 

are important in the implementation of this treatment. 

871 poster 

CONCURRENT CHEMORADIOTHERAPY IN LOCALLY ADVANCED 

NON-SMALL CELL LUNG CANCER: COMPARISON OF TWO TREAT- 

MENT REGIMENS 

M. Leclerc 1 , Y. Lacasse 2 , B. Raby 2 , F. Laberge 2 , B. Fournier 2 , S. Martin 

2 

1 HÔTEL-DIEU DE QUÉBEC, CENTRE HOSPITALIER UNIVERSITAIRE DE 

QUÉBEC (CHUQ), Département de Radio-Oncologie, Québec, Canada 

2 HÔPITAL LAVAL, INSTITUT UNIVERSITAIRE DE CARDIOLOGIE ET DE 

PNEUMOLOGIE, Clinique d’oncologie ambulatoire, Centre de pneumologie, 

Québec, Canada 

Purpose: The primary objective was to compare overall survival and secondary 

objectives were to examine failure-free survival, response rates and 

toxicity between two regimens of concurrent chemo-radiotherapy (CALGB 

9431 and SWOG S9504). 

Materials: We conducted a retrospective analysis of all patients treated with 

either protocol in our institution from November 2004 to September 2007. 

CALGB 9431 consisted of cisplatin and vinorelbine given as induction followed 

by concomitant chemoradiotherapy. SWOG S9504 consisted of cisplatin 

and etoposide given concomitantly with radiotherapy followed by consolidation 

docetaxel. 

Results: 28 patients were treated with CALGB 9431 and 53 with SWOG 

S9504; 68 patients contributed to the analysis (20 in CALGB 9431 and 48 in 

SWOG S9504). The two groups were similar in age, sex, stage, histology, 

weight loss and comorbidities at the time of diagnosis. Median follow-up in 

CALGB 9431 and SWOG S9504 was 20 and 11 months, respectively. There 

were significantly more partial responses in SWOG S9504 (70% vs. 40%). 

However, we did not observe significant differences in 2-year overall survival 

(CALBG 9431: 50% vs. SWOG S9504: 53%; log rank test, p=0.92) and 

failure-free survival (CALGB 9431: 15% vs. SWOG S9504: 31%; log rank 

test, p=0.88). Severe neutropenia occurred more frequently in CALGB 9431 

(74% vs. 13%; p

873 poster 

CRITICAL NORMAL TISSUES DOSE FOR NON SMALL CELL LUNG 

CANCER TREATMENT USING 3-D CONFORMAL RADIOTHERAPY 

D. Karacetin 1 , E. Kemikler 2 , S. Karaman 2 , A. Cakýr 2 , N. Tenekeci 2 , E. 

Kaytan Saglam 2 , E. N. Oral 2 , A. Kizir 2 

1 

SISLI ETFAL RESEARCH AND TRAINING HOSPITAL, Radiation Oncology, 


2 

ISTANBUL UNIVERSITY, Radiation Oncology, Istanbul, Turkey 

Purpose: To estimate the doses to the lung, heart, esophagus and spinal 

cord in stage III, Non Small Cell Lung cancer (NSCLC) radiotherapy used 3- 

D conformal radiotherapy.In locally advanced lung cancer , the use of radiotherapy 

and /or concurrent chemoradiotherapy is associated with significant 

pulmoner, cardiac and esophagial toxicity. While modern radiotherapy techniques 

have reduced radiation exposure to the heart, lung, esophagus and 

spinal cord, they have not eliminated. In this prospective study ,we analysed 

the levels of doses effecting crictical normal tissues ,during application of 3 D 

conformal radiotherapy 

Materials: Yn this study, 24 patients who were treated using 3-D conformal 

radiotherapy. with stage III non small cell lung cancer (NSCLC) , were 

considered. After, CT- simulatation, the fields were marked with the help of 

Radiologists. As lungs, heart (left and right atrium and left and right ventricle) 

, esophagus and spinal cord. volumes were calculated and Dose-volume 

histogrammes were created. Chemoraidiotherapy were used in these patients,after 

induction chemotherapy. The target included the primary tumor 

and regional nodes. The goal was to deliver 66 Gy to the planing target volume 

(PTV) in 33 daily fractions ( 46 Gy to electively treated mediastinum) 

while meeting multiple normal tissue dose constraints. Lung V(20), V(30), 

V(40) and mean lung dose, heart V(30), esophagus V(50) , spinal cord V(50) 

and mean doses were calculated. 

Results: Our statistical evaulation was made using SPSS method ,and we 

found crictical normal tissues doses following; Lung V20 was 3547 cGy (min 

190- max 6098) ,V30 2492 (min. 22- max. 5136), mean lung dose was 

1762 (min. 739-max.3339). Heart mean dose was1892 (min.22-max.4084), 

V30 25330 (min. 18-max.5779). Right atrium mean dose was 1770(min.3max.6128) 

, V30 2013 (min.0-max.6285). Left atrium mean dose was 2988 

(min.26-max.5850), V30 3753 (min.28-max.6158). right ventricile mean dose 

was1237 (min.1-max.3925), V30 1485(min.0-max.4276). Left ventricile mean 

dose was 1542 (min.0-max.4513). Spinal cord mean doses was 1201 (min 

115-max.2139). Esophagus mean dose was 2700 (min.912-max.4513). 

Conclusions: Because of stage III, bulky tumors , protection of crictical normal 

tissues were limited. Acute side effects were observed ; 18 patients had 

grade 1-2 esophajit, 2 patients had grade 3-4 pnomonitis, and 2 patients had 

grade 1-2 pnomonitis. The use of 3-D conformal radiotherapy, has the ability 

to reduce normal tissue toxicity, but has limited potential for dose escalation 

in node positive patients. 

874 poster 

CROSS-CULTURAL APPLICATION OF THE EORTC QLQ-C30 AND 

QLQ-LC13: IMPACT OF SOCIAL EPIDEMIOLOGIC FACTORS ON 

QUALITY OF LIFE IN LUNG CANCER PATIENTS 

F. Ataman 1 , N. Songur 2 , S. Ay 3 , S. Kaya 2 , A. Bottomley 4 

1 SULEYMAN DEMIREL UNIVERSIRTY, Radiation Oncology, Isparta, Turkey 

2 SULEYMAN DEMIREL UNIVERSIRTY, Chest Disease, Isparta, Turkey 

3 CELAL BAYAR UNIVERSIRTY, Public Health, Manisa, Turkey 

4 EORTC DATA CENTER, Quality of Life Unit, Brussels, Belgium 

Purpose: Lung cancer patients’ QoL is contemporary measured by the 

widely used EORTC QLQ-C30 core and lung cancer specific EORTC QLQ- 

LC13 questionnaires(Qs).The purpose of this work is to assess QoL scales 


S 279 

and their association with socio-economic(SE) and -cultural(SC) factors in 

lung cancer patients. 

Materials: The Turkish version of the two Qs were self-administered by a 

cohort of 38 lung cancer patients received surgery and/or radiation and/or 

chemotherapy. The effect of SE and SC factors on the symptom scales of the 

both Qs were investigated. The domains of EORTC QLQ-C30 was 5 functioning 

scales of physical(PF), role (RF), emotional (EF), cognitive (CF), social 

(SF), 3 symptom scales (fatigue, nausea and vomiting, pain), one global 

health status, six single items (dyspnoea, insomnia, appetite loss, constipation, 

diarrhea, financial difficulties). The EORTC QLQ-LC13, a supplementary 

module, which included symptom scales of dyspnoea, coughing, haemoptysis, 

sore mouth, dysphasia, peripheral neuropathy, alopecia, chest pain, arm 

&shoulder pain, and pain in other parts. We examined the effects of age (>60 

vs. ≤60 years), gender, marital status (married vs. unmarried), educational 

level (not have any school education vs. graduated from primary school or 

higher), household-size (small vs. large), income (income lower vs. average 

or more) on QoL domains. The analysis was done using relevant EORTC 

Scoring Manual procedures and SPSS program. The effecting factors was 

analyzed by Mann-Whitney U test and multiple linear regression (MLR). 

Results: The median age of the 38 patients was 61 (range, 30-77). Only 

3 patients (8%) were female. There were 29 non-small cell (76%) cancer 

and 9 small cell (24%) lung cancer patients. Thirty-six patients (95%) were 

married. Seven patients (18%) did not have any school education, whereas 

the rest had finished secondary school or higher. Twelve patients (12%) had 

definitive surgery, 27 patients (71%) received chemotherapy, and 9 patients 

(24%) received radiotherapy. Twenty-four patients (63%) had a average or 

more income and 14 patients (37%) had a lower income. The MLR analysis 

for the EORTC QLQ-C30 indicated small family, male gender, primary school 

or more higher education, average or more income increased SF, RF, EF, 

constipation, respectively(p


876 poster 

DEVELOPMENT AND EXTERNAL VALIDATION OF A PREDICTION 

MODEL FOR SURVIVAL OF NON-SMALL CELL LUNG CANCER 

PATIENTS TREATED WITH (CHEMO) RADIOTHERAPY: IDENTIFI- 

CATION OF A SUBGROUP WITH A GOOD PROGNOSIS. 

C. Dehing 1 , S. Yu 2 , D. De Ruysscher 1 , S. Meersschout 3 , K. Van Beek 4 , 

Y. Lievens 4 , J. Van Meerbeeck 3 , W. De Neve 3 , G. Fung 2 , B. Rao 2 , S. 

Krishnan 2 , P. Lambin 1 

1 


2 

SIEMENS MEDICAL SOLUTIONS, Malvern, USA 

3 

UNIVERSITY HOSPITAL GHENT, Lung Oncological Network Ghent, Ghent, 

Belgium 

4 

UNIVERSITY HOSPITAL LEUVEN, Radiotherapy, Leuven, Belgium 

Purpose: Radiotherapy, combined with chemotherapy, is treatment of choice 

for a large group of non-small cell lung cancer (NSCLC) patients. However, 

clinical TNM stage is highly inaccurate for the prediction of survival of nonsurgical 

patients and alternatives are currently lacking. The objective of this 

study was to develop and validate a prediction model for survival of NSCLC 

patients, treated with (chemo) radiotherapy. 

Materials: Clinical data from 403 consecutive inoperable NSCLC patients, 

stage I-IIIB, treated radically with (chemo) radiation were collected. A prognostic 

model for 2-year survival was developed, using 2-norm Support Vector 

Machines. Performance of the model was expressed as the AUC (Area Under 

the Curve) of the Receiver Operating Characteristic (ROC) and assessed using 

leave-one-out (LOO) cross-validation. External validation was performed 

in two independent datasets from Ghent and Leuven. The maximum value 

of the AUC is 1.0; indicating a perfect prediction model. A value of 0.5 indicates 

that patients are correctly classified in 50% of the cases, e.g. as good 

as chance. In addition, a risk score was calculated by dividing each model 

coefficient by the smallest coefficient and rounding it to the nearest integer. A 

nomogram, which is in fact a graphical representation of the risk score, was 

made for practical use. 

Results: The final multivariate model consisted of gender, WHO performance 

status, forced expiratory volume (FEV1), number of positive lymph node stations 

and gross tumor volume. The AUC, assessed by LOO cross-validation, 

was 0.75, while application of the model to the external datasets yielded an 

AUC of 0.75 and 0.76 respectively. Splitting the MAASTRO cohort into 3 

subgroups, based on the risk score, resulted in the identification of a high, 

medium and low risk group. The 2-year survival (S2) was 66% (95% CI 54%- 

78%) for the low risk group, 29% (95% CI 21%-37%) for the medium risk 

group and 14% (95% CI 5%-23%) for the high risk group. According to this 

risk stratification 17 patients (14.8%) with a clinical T3 or T4 tumor, 18 patients 

(12.5%) with a clinical N2 or N3 stage, and 26 patients (14.1%) with a 

clinical stage III were included in the low risk group. 

Conclusions: The model successfully estimates 2-year survival of individual 

patients and the performance, assessed internally as well as in two independent 

datasets, is good. A patient group with a good prognosis, having a 

2-year survival of 66%, could be identified. This group also included clinical 

T3-4 tumors. The model could assist clinicians in clinical decision-making 

and treatment tailoring. 

877 poster 

DOES PET- CT IN THE RADIOTHERAPY TREATMENT PLANNING 

PROCESS FOR NON-SMALL CELL LUNG CANCER REDUCE 

INTER-OBSERVER VARIABILITY? 

G. Hanna 1 , K. Carson 2 , J. McAleese 3 , V. Cosgrove 4 , D. Stewart 3 , R. 

Eakin 3 , A. Zatari 4 , L. Young 5 , J. Clarke 6 , J. O’Sullivan 1 , T. Lynch 7 , A. 

Hounsell 4 

1 

1. CENTRE FOR CANCER RESEARCH AND CELL BIOLOGY, QUEEN?S 

UNIVERSITY BELFAST., Department of Radiation Oncology, Belfast, United 

Kingdom 

2 

ROYAL VICTORIA HOSPITAL, BELFAST, Northern Ireland Regional Medical 

Physics Agency, Belfast, United Kingdom 

3 

CANCER CENTRE, BELFAST CITY HOSPITAL, Department of Clinical 

Oncology, Belfast, United Kingdom 

4 

CANCER CENTRE, BELFAST CITY HOSPITAL, Northern Ireland Regional 

Medical Physics Agency, Belfast, United Kingdom 

5 

CANCER CENTRE, BELFAST CITY HOSPITAL, Therapeutic Radiography, 

Belfast, United Kingdom 

6 

ROYAL VICTORIA HOSPITAL, BELFAST, Department of Nuclear Medicine, 

Belfast, United Kingdom 

7 

CANCER CENTRE, BELFAST CITY HOSPITAL, Department of Nuclear 

Medicine, Belfast, United Kingdom 

Purpose: CT is the gold standard for gross tumour volume (GTV) definition in 

the treatment planning process for the radical treatment of non-small cell lung 

cancer (NSCLC) with radiotherapy (RT). Despite technical improvements in 

RT delivery, increased use of systemic therapies and more accurate staging, 

survival remains poor. It has been shown that PET-CT is more accurate than 

CT alone in the staging of NSCLC and that PET alters GTV in the RT planning 

process. We seek to examine the impact of using combined PET-CT images 

for GTV definition in the NSCLC in patients whose disease has already been 

fully staged with PET-CT imaging. In particular we wish to assess whether 

PET-CT can reduce inter-observer variability in target definition. 

Materials: From March 2005 to June 2007, 28 patients with pathologically 

confirmed NSCLC stages IA to IIIB were enrolled in a PET-CT RT planning 

study. All patients had a staging PET-CT scan prior to consent to ensure 

they were suitable for radical radiotherapy. 14 patients received induction 

chemotherapy. In place of a planning RT CT scan, patients were scanned 

on a GE Discovery LS PET-CT scanner. All patients were treated based on 

their CT volumes. In a virtual planning study, 4 radiation oncologists (RO) 

independently delineated the GTV on the CT images alone, and then on the 

fused PET-CT images. The ROs had access to a complete set of diagnostic 

and clinical information for each patient including the staging PET-CT images. 

In-house software was used to compare the GTVs outlined. Intra-observer 

variability was compared using concordance index (CI). 

Results: There is an improvement in CI between observers when defining 

the GTV using the PET-CT images as opposed to using CT alone for matched 

cases (mean CI of 0.55 for CT and 0.59 for PET-CT, p=0.001). This difference 

is also present and highly significant in the subset of the induction chemotherapy 

group (mean CI 0.44 for CT and 0.49 for PET-CT, p1cm diameter) (2) GTVPET: drawn using the fused 

PET-CT and defined using a standard threshold value of 42% of the maxi-

mum PET standard uptake value (SUV). An isotropic margin of 0.8cm was 

extended from both GTVCT,PET to define CTVCT,PET and a further expansion 

of 1-1.5cm to generate PTVCT,PET, depending on tumour location. 3D 

treatment plans were generated using PTVPET using OMP v.3.0. Dose volume 

constraints (DVC) to PTVPET were based on ICRU 50/62 with respect 

to homogeneity and coverage. For the organs at risk (OR) institutional constraints 

of Dmax < 44Gy for the spinal cord, V50


with contrast CT: 1/10 (10%) patients had CR at PET, but PD at a successive 

PET/CT, six months later, 4/10 (40%) patients had PR , 5/10 (50%) PD (3 at 

PET, 2 at contrast CT). Five patients are alive, with 5 months (1-22) of median 

survival from the beginning of HT. 

Conclusions: The 5 responses to treatment, in patients who were essentially 

palliative, and the good toxicity profile (none greater than G2) indicates that 

HT is a good option in the treatment of MPM. Our next step will be the addition 

of a simultaneous boost in the most active areas at PET/CT (BTV). 

881 poster 

HYPOFRACTIONATED RADIOTHERAPY IN ELDERLY PATIENTS 

WITH MEDICALLY INOPERABLE STAGE I-II NON-SMALL-CELL 

LUNG CANCER 

P. Bonfili 1 , M. Di Staso 1 , G. L. Gravina 1 , P. Franzese 1 , F. Soldà 1 , A. 

Piscopo 1 , V. Tombolini 1 

1 UNIVERSITY OF L’AQUILA, Radiotherapy, L’Aquila, Italy 

Purpose: We analyzed the results of hypofractionated-radiotherapy (HFRT) 

and prognostic factors in a cohort of elderly patients with medically inoperable 

stage I-II non-small-cell-lung cancer (NSCLC). For this purpose, the primary 

endpoint of study was report the OS associated with treatment at 2 years. As 

secondary outcome measures, we assessed cause-specific-survival (CCS), 

disease-free-survival (DFS) and local control at 2 years. Additionally, side 

effects associated with radiotherapy were also recorded. 

Materials: Between November 2003 and December 2005, 24 patients were 

treated with HFRT. radiotherapy was performed with a dose of 60 Gy in 20 

daily fractions with 3 Gy per fraction. Squamous-cell-carcinoma (SCC) was 

diagnosed in 17 patients and 7 patients were diagnosed with adenocarcinoma. 

To evaluate association between potential prognostic factors and OS, 

a univariate Cox proportional hazard analysis was performed to obtain hazard 

ratio (HR) and CI 95%. The prognostic factors evaluated were: sex, stage 

(I vs. II), KPS, tumor histology and tumor size. All statistical analyses were 

performed using the SPSS R○statistical analysis software package, version 

10.0. With an intention to treat-strategy all patients were included in the final 

analysis. 

Results: At 2-years the overall-survival (OS), the cause-specific-survival 

(CSS) and the disease-free-survival were 58.3%, 62.5%, and 41.7% respectively. 

The median OS, CSS, and DFS were 21 months (22.9 to 33.3), 27.9 

(26.3 to 34.1), and 24.7 (19.9 to 31.2) respectively. At univariate analysis the 

only factors significantly influencing OS were the KPS> 90 (HR 1.056;95% 

CI 1.013 to 1.101) and tumor size< 4 cm (HR 0.890;95%CI 0.735 to 0.929). 

Local control was 70.8% at 2 years. No grade 3-4 acute toxicity was reported. 

Grade-2 oesophagitis was reported in 3 cases, dry cough in 5 patients with 

grade-1 dyspnoea in two cases. In 1 patient was radiologically observed a 

late lung fibrosis of grade-1. No significant changes in lung function parameters 

were found at 6 and 12 months after radiotherapy. 

Conclusions: This series, including elderly patients with medically inoperable 

stage I-II NSCLC, showed that HFRT is safe in these patients. The 

median survival was encouraging. Long-term results will be necessary to 

confirm these results. 

882 poster 

HYPOFRACTIONATED RADIOTHERAPY WITH STEREOTACTIC 

LOCALIZATION IN EARLY STAGE NON SMALL CELL LUNG CANCER 

(NSCLC) 

F. Salvi 1 , G. Frezza 1 , E. Dononi 1 , L. Vicenzi 1 , A. Baldissera 1 , C. 

Degli Esposti 1 , O. Martelli 1 , F. Monari 1 , F. Spagnolli 1 , P. Chiovati 2 , M. 

Palombarini 2 , R. Romagnoli 2 

1 BELLARIA HOSPITAL, Radiotherapy, Bologna, Italy 

2 BELLARIA HOSPITAL, Medical Physics, Bologna, Italy 

Purpose: To evaluate the response rate, survival and the toxicity of hypofractionated 

radiotherapy (50-55 Gy/5 fractions) in patients affected by early stage 

(T1-T2 15 

Gy at < 10%. Irradiation was given with 4-6 fixed non coplanar and coplanar 

beams of 10 MV photons, shaped with a MLC aiming to encompass the PTV 

with 80% isodose. We considered the pulmonary mean dose (425 cGy) and 

the V12 (mean value 10.9%) as possible factors of complication risk. Mean 

dose to PTV ranged from 4766 to 5451 cGy. Treatment was performed on 5 

consecutive daily fractions (fx). 

Results: Mean follow up was 24 months (range: 1-64 months). Response 

was evaluated with chest CT scan and/or PET scan with 18 FDG. 29 pts are 

alive (22 without evidence of disease progression). Death was cancer related 

only in 16/28 pts. 2 pts. are lost at the follow up, without progression of disease 

after 13 and 18 months respectively from the end of treatment. Distant 

metastases were the first cause of failure. We observed only 5 isolated local 

disease progressions in the site of treatment. Acute and late toxicity more 

then grade 2, scored according to RTOG criteria, and a reduction of FEV1 > 

10% were never observed. 

Conclusions: Hypofractionated (50Gy/5fx) SRT in early stage NSCLC gives 

a high response rate with acceptable toxicity but further follow up is necessary 

to determine if this observation is related to an improvement of survival rate. 

883 poster 

HYPOFRACTIONATED STEREOTACTIC RADIOTHERAPY (HSRT) IN 

PRIMARY OR RECURRENT NON-SMALL CELL LUNG CANCER 

F. Zimmermann 1 , U. Schratzenstaller 1 , S. Schill 2 , H. Geinitz 2 , S. Astner 

2 , A. Papachristofilou 1 , M. Molls 2 

1 UNIVERSITY CLINIC, Institute of Radiation Oncology, Basel, Switzerland 

2 UNIVERSITY CLINIC, Clinic of Radiation Oncology, Munich, Germany 

Purpose: For inoperable patients with early stage non-small cell lung cancer 

(NSCLC) and/or locally recurrent cancer after previous thoracic radiotherapy, 

HSRT has been introduced as treatment of choice in Munich in 2000 and in 

Basel in 2008. 

Materials: We report on 81 patients with early stage NSCLC (cT 1-2 cN0 

cM0)(group 1), and 18 patients with local or regional recurrence of NSCLC 

after previous thoracic radiotherapy (group 2)(median age 76 (59-92) years), 

treated between December 2000 and January 2007 by HSRT (mean BED 

with a/b=3: 193.75 (88-270),mean BED with a/b=10: 84.4 (43.2-112.5) in surrounding 

60 %-isodose). Mean follow-up is 23 (3-60) months. Target volume 

was visible tumour in lung and mediastinal window as well as FDG-PET-scan, 

with safety margin for planning target volume of 3-12 mm for positioning of the 

patient and 6-22 m for breathing excursions. All pat. had complete staging 

with CT-scan of thorax, abdomen and brain (in Adenocarcinoma) as well as 

FDG-PET before radiotherapy. 

Results: Local tumor control is 88 % and 81 %, and cancer-specific-survival 

at 3 years 73 % and 32 % for group 1 and 2, respectively. In each group, 2 

patients died from local recurrence, but 25 % and 60 % from distant metastases 

in group 1 and 2, respectively. Side effects were mild in both groups, 

with pneumonitis III ◦ CTC of 3 % and 5.5 %, and pneumonitis II ◦ of 25 % 

and 11 % in group 1 and 2, respectively, and no treatment-related mortality. 

Conclusions: HSRT of early stage NSCLC and/or local/regional tumor recurrence 

even after previous thoracic radiotherapy is feasible with low rate of 

severe side effects, but high local control rates. Distant metastases are the 

main cancer-related cause of death, and systemic therapy should be taken 

into account in younger patients. 

884 poster 

IMRT IN COMBINATION WITH CETUXIMAB IN THE TREATMENT 

OF NSCLC: THE NEAR TRIAL (NCT 00115518): TOXICITY AND 

PRELIMINARY RESULTS 

A. D. Jensen 1 , M. W. Münter 1 , H. Bischoff 2 , R. Haselmann 1 , C. Timke 

1 , R. Krempien 1 , F. Sterzing 1 , S. Nill 3 , S. Heeger 4 , A. Hoess 3 , U. 

Haberkorn 5 , P. Huber 6 , M. Steins 2 , M. Thomas 2 , J. Debus 1 , K. Herfarth 

1 

1 

UNIVERSITY OF HEIDELBERG, Radiation Oncology, Heidelberg, Germany 

2 

THORAXKLINIK HEIDELBERG, Medical Oncology, Heidelberg, Germany 

3 

GERMAN CANCER RESEARCH CENTRE (DKFZ), Medical Physics, 


4 

MERCK KGAA, Darmstadt, Germany 

5 

UNIVERSITY OF HEIDELBERG, Nuclear Medicine, Heidelberg, Germany 

6 

GERMAN CANCER RESEARCH CENTRE (DKFZ), Clinical Cooperation Unit 


Purpose: Treatment of stage III NSCLC still poses a serious therapeutic challenge. 

In case surgical resection is impossible, combined RCHT is the treatment 

of choice, though sometimes accompanied with marked side-effects. 

Many patients are not eligible for combined modality treatment due to comorbidities. 

Besides, we are often faced with very large primary tumours 

hence adequate dosage in conventional RT techniques rarely succeeds due 

to doses to surrounding normal tissue. Within the NEAR trial, patients are 

treated with weekly EGFR-antibody cetuximab and intensity-modulated RT.

Aim of the trial is to evaluate toxicity and tumour response. 

Materials: The CTV includes the primary tumour plus locoregional lymph 

nodes and receives a dose of 50 Gy (2Gy/ Fx). The GTV including primary 

tumour and PET-positive areas is subsequently boosted to 66 Gy (2Gy/ 

Fx). Optimisation of IMRT is achieved using inverse planning in our Kon- 

Rad planning system. Subsequent dose calculation is done on VIRTUOS 

(Version 4.4.9) using superposition algorithms. Dose distributions of primary 

and boost plans are added using voxel-by-voxel addition in order to evaluate 

resulting DVHs. Treatment duration is approx. 4 months incl. 13 adjuvant 

weekly courses of cetuximab. Staging and follow-up include CT-thorax, FDG- 

PET, and lung function tests. 

Results: 22 of 30 pts aged 57-82 years (median 71 a) could be included so 

far. Median follow-up is 14 months (2-29). 2 pts are still on treatment, one 

pt died prior to treatment end. Overall, treatment was very well tolerated: 

there was only one case of therapy-related ◦ 3 morbidity (oesophagitis). All 

pts showed acneiforme skin reactions ( ◦ I) typical for treatment with EGFRinhibitors. 

Higher grade skin toxicity has not been observed. According to 

RECIST, 15/20 pts showed PR, 4/13 pts SD. All pts exhibited a marked reduction 

of SUV in their f/u PET scans. Tumour volumes treated were comparatively 

large ranging from [398-1531 ml] with a median of 739 ml for the 

PTV and from [100-529ml] with a median of 364 ml for the GTV. Hence, the 

median V20 was 29%, and the V15 and V10 38% and 47% respectively. 6/21 

patients developed pneumonitis (CTC ◦ I) as diagnosed on CT-scans, none of 

these changes proved symptomatic or required treatment. Maximum dose to 

oesophagus was 63 Gy (median), the mean dose was 38 Gy. 

Conclusions: The NEAR-trial has so far proved a reasonably safe treatment 

regimen with only mild side-effects and encouraging tumour response. No 

increase of toxicity could be demonstrated by the addition of cetuximab and 

IMRT even considering large treated volumes. 

885 poster 

INTERIM RESULTS OF CONCURRENT CHEMORADIATION THER- 

APY WITH CONTINUOUS PACLITAXEL INFUSION AND WEEKLY 

CISPLATIN FOR STAGE III NON-SMALL CELL LUNG CANCER 

S. H. Lee 1 , L. Kyu Chan 1 , C. Jin-Ho 1 , C. Eun Kyung 2 , P. Se Hoon 2 , J. 

Sung Whan 2 , P. Jeong Woong 2 , P. Soo-Jin 3 

1 GIL MEDICAL CENTER, GACHON UNIVERSITY OF MEDICINE AND SCIENCE, 

Radiation Oncology, Incheon, Korea Republic of 


Department of Internal Medicine, Incheon, Korea Republic of 


Radiology, Incheon, Korea Republic of 

Purpose: In 2004, we reported the results of weekly paclitaxel concomitant 

with cisplatin and radiation therapy (RT), but this study was early closed because 

of unsatisfactory response rate (43.8%) and high grade 3-4 toxicities 

(75%). So, The chemotherapy protocol was amended from weekly paclitaxel 

to protracted continuous paclitaxel infusion during RT. The aim of this study 

was to evaluate the outcome and efficacy of continuous paclitaxel infusion, 

weekly cisplatin and concurrent RT for stage III non-small cell lung cancer 

(NSCLC). 

Materials: Between January 2003 and May 2006, twenty-six patients with locally 

advanced stage III NSCLC received paclitaxel and cisplatin with concurrent 

RT. Patients were treated with thoracic RT with continuous paclitaxel 40 

mg/m 2 infusion and weekly cisplatin 20 mg/m 2 throughout the RT. A median 5 

cycles (range: 3~8) of chemotherapy were performed. Radiation therapy was 

delivered with 1.8 Gy daily fractions to a total dose of 50.4~74 Gy (median: 

66 Gy) in 7~8 weeks. 

Results: The follow-up period was 3.7~62.5 months (median: 18.7 months). 

The overall response rate was 57.7%. The median overall survival time was 

18.9 months and the 1-year and 2-year overall survival rates were 64% and 

43.2%, respectively. The median progression survival time was 11.6 months 

and the 1-year and 2-year progression-free survival rates were 50.0% and 

41.5%, respectively. Locoregional failure occurred in 26.9% (7/26). Distant 

metastases were found in 30.8% (8/26). On univariate analysis of overall 

survival, tumor response (p=0.002) and pathology (p


888 poster 

LUNG CANCER RADIOTHERAPY USING 3D-CRT, MLC-BASED 

IMRT AND HELICAL TOMOTHERAPY 

M. Delichas 1 , P. Mavroidis 2 , B. Costa Ferreira 3 , C. Shi 4 , A. Gutierrez 4 , 

B. Lind 2 , N. Papanikolaou 4 , C. Ha 4 

1 ARISTOTLE UNIVERSITY OF THESSALONIKI, Department of Medical 

Physics, Medical School, Thessaloniki, Greece 



3 UNIVERSITY OF AVEIRO, I3N Physics, Aveiro, Portugal 

4 UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER, Department of 


Purpose: The effectiveness of 3D-Conformal Radiotherapy (3D-CRT), Intensity 

Modulated Radiotherapy (IMRT) using Multileaf Collimators (MLC) and 

Helical Tomotherapy (HT) has been an issue of increasing interest over the 

past few years. The biologically effective uniform dose (BEUD) together with 

the complication-free tumor control probability (P+) are used together with 

common dosimetric criteria to evaluate the three radiation modalities. 

Materials: Four lung cancer cases have been investigated by developing a 

3D-CRT treatment plan, a linac MLC-based step-and-shoot IMRT plan and a 

Helical Tomotherapy plan for each. The 3D-CRT and the MLC-based IMRT 

treatment plans were developed on the Philips treatment planning station using 

the Pinnacle 7.6 software release while the dedicated Tomotherapy treatment 

planning station was used for the HT plans. The three sets of treatment 

plans were evaluated and compared based on dosimetric measures such as 

DVHs, mean, maximum and minimum doses. Furthermore, radiobiological 

measures such as the P+ index and the BEUD concept were also used. 

Results: For the examined lung cancer case, the average 3D-CRT dose distribution 

appears to be inferior than the MLC-based IMRT and HT treatment 

plans, which appear to be almost equivalent over the clinically useful dose 

prescription range. More specifically, the avarage 3D-Conformal, MLC-based 

IMRT and HT treatment plans give a P+ of 55.4%, 72.9% and 66.9%, for a 

BEUD to the internal target volume (ITV) of 57.0Gy, 66.9Gy and 64.0Gy, respectively. 

The complication-free tumor control could be increased by almost 

5% if dose prescription could be optimized allowing a risk for complications 

higher than 5%. This is illustrated in the figure by plotting the P+, total control 

probability, PB and total complication probability, PI curves against the BEUD. 

Conclusions: The ability of both the MLC based-IMRT and HT to produce 

dose distributions of high conformality is considerably larger than that of the 

3D-CRT. In this sense they can cover PTV with a higher dose sparing at the 

same time the organs at risk. This is expected to lead to increased tumor control 

and reduced risk for complications as it is indicated by the radiobiological 

treatment plan evaluation and the dose-response relations of the irradiated 

tumors and normal tissues. In order to compare and effectively evaluate different 

treatment plans, the use of P - BEUD diagrams can compliment the 

traditional tools of evaluation. 

889 poster 

MULTI-DISCIPLINARY MANAGEMENT OF ADVANCED STAGE III 

NON SMALL CELL LUNG CANCER (NSCLC): PRELIMINARY RE- 

SULTS OF A PHASE TWO TRIAL WITH NEOADJUVANT CISPLATIN 

AND GEMCITABINE AND CONCURRENT RADIOTHERAPY. 

G. Mantini 1 , V. Valentini 1 , B. Meduri 1 , M. Massaccesi 1 , F. Maggi 2 , A. R. 

Larici 2 , S. Valente 3 , F. M. Corbo 3 , A. Mulè 4 , M. L. Calcagni 5 , A. Cesario 

6 , M. T. Congedo 6 , S. Margaritora 6 , P. Granone 6 

1 

POLYCLINIC UNIVERSITY "A. GEMELLI", CATHOLIC UNIVERSITY, Radiotherapy, 

Rome, Italy 

2 

POLYCLINIC UNIVERSITY "A. GEMELLI", CATHOLIC UNIVERSITY, Radiology, 

Rome, Italy 

3 

POLYCLINIC UNIVERSITY "A. GEMELLI", CATHOLIC UNIVERSITY, Department 

of Respiratory Physio-Pathology, Rome, Italy 

4 

POLYCLINIC UNIVERSITY "A. GEMELLI", CATHOLIC UNIVERSITY, Pathology, 

Rome, Italy 

5 

POLYCLINIC UNIVERSITY "A. GEMELLI", CATHOLIC UNIVERSITY, Nuclear 

Medicine, Rome, Italy 

6 

POLYCLINIC UNIVERSITY "A. GEMELLI", CATHOLIC UNIVERSITY, Department 

of General Thoracic Surgery, Rome, Italy 

Purpose: Many clinical trials showed a relationship between pathological 

down staging after neo-adjuvant therapy and survival in patients with stage III 

NSCLC. In our Institution we tested the feasibility and efficacy of neo-adjuvant 

Concurrent Radio-Chemotherapy (CRCT) with weekly Gemcitabine (GEM) 

followed by surgery, in patients with stage III NSCLC; 18/46 (39%) patients 

showed a pathologic down-staging to stage 0 or I and their overall 2-yr survival 

was 66.1%. Aim of this trial was to evaluate the safety and efficacy of a 

multimodality regimen consisting of CRCT with GEM plus Cisplatin (CDDP) 

followed by surgery. 

Materials: Patients with clinical stage III (IIIA: N2 or IIIB: T4 mediastinum 

or great vessels invasion) NSCLC entered in a protocol of CRCT consisting 

of CDDP (20 mg/m2/day for 4 consecutive days, every 4 weeks) and 

GEM (350 mg/m2/day, weekly) and conformal radiotherapy (total dose 50.4 

Gy). Surgery was performed in those patients judged to be resectable at 

re-staging. The analysis of proportion of major down-staging with H0 ("bad" 

response probability, previous study) and H1 ("good" response probability, 

ongoing study), was performed by single proportion test and the validation of 

the accrual was determined by the single proportion powered analysis (Systat 

11, SPSS Science, Chicago, IL USA). 

Results: Between August 2003 and May 2007, 39 patients (median age 63) 

with clinical stage III NSCLC (16 IIIA and 23 IIIB) were enrolled. G3 (RTOG) 

oesophagitis was recorded in 3/39 (8%) patients. 6/39 (15%) patients complained 

dysphagia G2. 1 patient (2.5%) developed radiation pneumonitis 

G3; another one showed pulmonary toxicity G2. Haematological toxicity was 

mild. 34/39 (87%) patients underwent radical resection: 8 pneumonectomies 

were performed. Four post-operative major complications were described; 2 

(5.7%) post-operative death occurred. Pathologic down-staging to stage 0 

or I was observed in 24/39 patients (62%), 12/39 (31%) patients showed no 

residual disease at pathologic examination. At the single proportion test the 

proportion of major down-staging was significantly higher than the proportion 

observed with only GEM (p=0.005). The number of observed patients (39) is 

consistent with the number required (35) to detected a difference of 62% vs 

39%, according to single proportion powered analysis (α= 0.05, power= 0.8). 

Conclusions: In our experience, neo-adjuvant CRCT with CDDP and GEM 

provided significant better outcome in terms of pathologic down-staging than 

our previous phase II study at price of moderate toxicity. 

890 poster 

MULTIMODALITY TREATMENT OF STAGE III NON-SMALL CELL 

LUNG CANCER: EARLY RESULTS OF A PHASE II TRIAL USING 

PREOPERATIVE CISPLATIN AND GEMCITABINE WITH CONCUR- 

RENT RADIOTHERAPY 

R. M. D’Angelillo 1 , S. Ramella 1 , F. Cellini 1 , A. Cesario 2 , M. Ciresa 1 , M. 

Fiore 1 , C. Greco 1 , E. Pompeo 3 , T. C. Mineo 3 , P. Granone 4 , L. Trodella 1 

1 CAMPUS BIO-MEDICO UNIVERSITY, Radiotherapy, Rome, Italy 

2 CATHOLIC UNIVERSITY; IRCCS SAN RAFFAELE, Division of General 

Thoracic Surgery; Pulmonary Rehabilitation, Rome, Italy 

3 TOR VERGATA UNIVERSITY, Division of Thoracic Surgery, Rome, Italy 

4 CATHOLIC UNIVERSITY, Division of General Thoracic Surgery, Rome, Italy 

Purpose: We report the preliminary results of a phase II trial exploring the 

efficacy and the feasibility of combination of gemcitabine and cisplatin concurrent 

with radiotherapy followed by surgery in patients with stage III non-small 

cell lung cancer (NSCLC). 

Materials: Patients, with histo-cytologically confirmed NSCLC and deemed 

unresectable for stage IIIAN2 or IIIB-T4 disease, were treated according to 

a combined chemo-radiation protocol with Cisplatin, 80 mg/mq the first and 

last week of treatment, and weekly Gemcitabine, 300-350 mg/mq. Involved 

field Radiotherapy was delivered up to 50.4 Gy, with daily fractionation of 

1.8 Gy/die. Pulmonary, esophageal, cardiac, hematological and skin toxicities 

were assessed. After radiological and pneumological re-assessment, pa-

tients judged operable underwent surgery. The study was designed according 

to Simon’s two stage phase II trial, with a target activity of 20% (established 

as a pathological dowstaging to stage 0-I), an a-error of 0.05 and a power of 

study of 80%; the early assessment was on 16 patients, while target sample 

size was 50-55 patients. 

Results: The evaluation performed on initial 16 patients showed a 43% activity 

of induction protocol with 7 patients who underwent radical surgery with a 

pathological downstaging to stage 0-I. Thus enrollement was carried on, and 

49 patients are actually enrolled. 46 are evaluable for acute toxicity, clinical 

and pathological response to treatment. Stage at diagnosis was IIIAN2 in 24 

patients and IIIBT4 for the remaining 22. Eight patients (17.4%) experienced 

acute grade 3-4 hemathological toxicity (mainly leucopenia without any febrile 

neutropenia), while acute grade 3 esophageal toxicity was recorded in 3 patients 

(6.5%). One patient developed a grade 4 pulmonary toxicity. Among 46 

patients response was recorded as follows: 38 (82.6%) Partial Response, 1 

No Change disease and 7 Progressive Disease (5 cases of distant progression). 

Thirty-five patients (76.1%) underwent to radical surgery. Pathological 

specimens showed a downstaging in 25 (54.3%) to stage 0-I, and in 5 (10.9%) 

as stage II disease. A stage III disease was histologically detected in the latter 

resected patients. 

Conclusions: The results of trial confirm the feasibility and the efficacy of 

gemcitabine and cisplatin concurrent with radiotherapy followed by surgery. A 

longer follow-up is needed to confirm the long term benefit of such treatment. 

891 poster 

N-STAGE, SURVIVAL AND HIPOFRACTIONATED RADIOTHERAPY 

IN NON-SMALL CELL LUNG CANCER 

J. L. Monroy Anton 1 , M. Soler Tortosa 1 , A. V. Navarro Bergadà 1 , M. Lopez 

Muñoz 1 , C. Gaspar Martinez 2 , R. Girones 3 

1 

HOSPITAL UNIVERSITARIO DE LA RIBERA, Radiation Oncology, Alzira, 

Spain 

2 

HOSPITAL UNIVERSITARIO DE LA RIBERA, Medical Oncology, Alzira, Spain 

3 

HOSPITAL LLUI ALCANYIS, Medical Oncology, Xativa, Spain 

Purpose: Radiotherapy fractionated schedules are used in lung cancer treatment 

for those patients in which high total doses with conventional fractionation 

are not appropriated: age, concomitant diseases, poor Kafnofsky index, 

etc. N-stage determines treatment volumes, tolerance and overall survival. 

The objective was to determine differences in survival, using three different 

schedules of hipofractionated external radiotherapy. 

Materials: We studied 53 patients diagnosed in our institution of non small 

cell lung cancer and treated with hipofractionated external radiotherapy (virtual 

simulation and 3D planning). None of the patients underwent surgery 

before or after radiotherapy. 25 patients received different schemes of 

chemotherapy. Aged ranged between 42-88 years (mean: 69.5, median: 

58.5). According N-stage, patients were divided in two groups: N0: 18 patients; 

N+ (1-3): 35. We use three different radiotherapy schedules: - 23 

patients received 3Gy in 10 fractions (10x3), total dose: 30Gy and two weeks 

treatment - 12 patients received 5Gy in 4 fractions (5x4), total dose: 20Gy 

and one week total treatment - 18 patients received 5Gy in 4 fractions in a 

two weeks treatment with a 2 weeks interval gap, total dose: 20Gy. Survival 

was measured in months since finish of radiation treatment to November 2007 

Results: All patients completed radiotherapy with no important acute sideeffects. 

We evaluated two situations: 1.- Mean survival time: - N0 patients: 

11 months in 10x3 schedule group; 22 m. in 5x4x2; 18 m. in 5x4. - N+: 

6 months for 10x3; 8 m for 5x4x2; 3m for 5x4. 2.- Survival longer than 6 

months: - N0 group: 12 patients alive (66.6%). Fractionation schedules: 4 

patients in 10x3 (33%); 6 patients (50%) in 5x4x2; 2 patients (17%) in 5x4. - 

N+: 13 patients alive (37%): 7 patients (54 %) in 10x3; 5 patients (38%) in 

5x4x2; only 1 patient (8%) in 5x4 

Conclusions: Hipofractionated radiation treatments are well tolerated in 

NSCLC patients in which high total doses are not adequate, even though 

N+ stage conduce to an increase in planning treatment volumes with theoretically 

consecutive increased toxicity. In both analysed groups (N0, N+), 5x4x2 

seems to be the best schedule in terms of mean survival. As we expected, 

survival in N0 patients is higher than N+, in all schemes. Analysing survival 

>6months, 5x4x2 presents higher proportion of patients alive in N0 group. 

However, in N+, 10x3 seems to be better schedule. The 5x4 scheme shows 

poor results, except in N0 mean survival. This could be a good fractionation 

for extremely fragile patients with negative N-stage or palliation in N+ tumors 

892 poster 

NSCLC: PRIMARY TUMOR SIZE - RADIATION DOSE RELATED, 

ACCELERATED, TWICE DAILY RADIOTHERAPY BY TARGET 

SPLITTING: A PROSPECTIVE DOSE-FINDING STUDY 

K. Wurstbauer 1 , H. Deutschmann 1 , P. Kopp 1 , M. Kranzinger 1 , F. Merz 1 , 

O. Nairz 1 , H. Schöller 1 , M. Studnicka 2 , F. Sedlmayer 1 

1 PARACELSUS MEDIZINISCHE PRIVATUNIVERSITÄT, University Clinic of 

Radiation Oncology, Salzburg, Austria 

2 PARACELSUS MEDIZINISCHE PRIVATUNIVERSITÄT, University Clinic of 

Radiation Pneumology, Salzburg, Austria 


S 285 

Purpose: Dose-finding correlating dose to primary tumor size in accelerated, 

twice daily radiotherapy of non-operated NSCLC patients. 

Materials: 1/04-12/07: 102 patients with 104 histologically/ cytologically 

proven tumors. Stage I: 24 pts.; II: 5; IIIA: 43; IIIB: 30. Weight loss >5%/3 

months: 26 patients. Slow planning CTs (4s/slice), patients freely breathing, 

margin GTV to PTV 7 mm. 4 groups according to primary tumor size (mean 

of 3 perpendicular diameters) / total dose / n: 6,0 cm/90,0 Gy/8. Macroscopically 

involved nodes 61,2 Gy median (range 54,0-75,6 Gy), nodes electively 45,0 

Gy (to volume about 6 cm cranially to apparently involved nodes). Single fraction 

1,8 Gy (ICRU), twice daily, interval 11h, 5 days/week, duration 33 days 

median (29-42). Use of conformal target splitting technique in most patients. 

Antimycotic prophylaxis for esophagitis with amphotericine B lozengers. In 

64 patients 2 cycles of chemotherapy before radiotherapy, no simultaneous 

chemotherapy. Modification of dose/size levels according to prospectively 

performed analysis intended. Median follow-up of all patients 17,6 months, of 

patients alive 19,2 m. 

Results: To 97% of the patients the intended dose has been applied. Until 

now 13 local recurrences (0/15, 6/57, 5/24, 2/8 in the respective groups) 

with an actuarial local tumor control rate at 2 years of 82%. 4 regional recurrences 

(3 of them in elective, previously not treated sites). Actuarial overall 

survival rate at 1 / 2 years is 79% / 58%, respectively; median 28,0 months. 

For 40 IIIA-N2 patients median survival is 30,1 months. 2 treatment-related 

deaths: pulmonary fibrosis 5 and 6 months after radiotherapy (in both patients 

preexisting pulmonary fibrosis did exist). Pneumonitis grade 3: 2 patients. 

Esophagitis grade 1: 27 pts., 2: 6 pts., 3: 5 pts. No late toxicity >grade 1. 

Conclusions: Locoregional tumor control is high. Until now no modification 

of dose and/or tumor size levels. Survival rates are promising. Patients with 

preexisting pulmonary fibrosis must be excluded. Accrual is continued. 

893 poster 

ONLY HALF OF LOCALLY ADVANCED LUNG CANCER PATIENTS 

ARE ELIGIBLE FOR CONCURRENT CHEMOTHERAPY AND RADIO- 

THERAPY: A PROSPECTIVE, POPULATION-BASED STUDY. 

A. Botterweck 1 , D. De Ruysscher 2 , M. Dirx 1 , M. Hochstenbag 3 , R. 

Wanders 4 , G. Bootsma 5 , W. Geraedts 6 , J. Simons 7 , C. Pitz 8 , P. Lambin 

2 

1 

COMPREHENSIVE CANCER CENTRE LIMBURG (IKL), Maastricht, Netherlands 

2 

UNIVERSITY MEDICAL CENTER MAASTRICHT, MAASTRO CLINIC, GROW, 

Radiation Oncology, Maastricht, Netherlands 

3 

UNIVERSITY MEDICAL CENTER MAASTRICHT, Department of Lung 

Diseases, Maastricht, Netherlands 

4 


5 

ATRIUM MEDICAL CENTER, Department of Pulmonology, Heerlen, 

Netherlands 

6 

MAASLAND HOSPITAL, Department of Lung Diseases, Sittard, Netherlands 

7 

SINT JANS GASTHUIS, Department of Lung Diseases, Weert, Netherlands 

8 

LAURENTIUS HOSPITAL, Department of Lung Diseases, Roermond, 

Netherlands 

Purpose: In most trials as well as in guidelines, patients with stage III nonsmall 

cell lung cancer (NSCLC) and limited stage small cell lung cancer 

(SCLC) are excluded from concurrent chemo-radiation mostly on the basis 

of co-morbidity and age. To get insight in what proportion of patients with 

stage III lung cancer would be suitable for concurrent chemo-radiation, we 

performed a prospective population-based study. 

Materials: From 2002 to 2005, all patients with a pathological diagnosis 

of lung cancer and clinical stage III in the Maastricht Cancer Registry, the 

Netherlands, were prospectively assessed for severe forms of the following 

co-morbidity: COPD, myocardial infarction, cardiac insufficiency, angina pectoris, 

CABG, intermittent claudication, abdominal aneurysm, cerebrovascular 

accident, hemiplegia, rheumatoid arthritis, renal failure, stomach ulcer requiring 

surgery, colitis, liver cirrhosis, hepatitis, dementia, chronic infections. Patients 

were excluded from concurrent chemo-radiation if they had one or more 

severe co-morbidity or were 75 years or older. 

Results: 711 patients were included, 577 with NSCLC and 134 with SCLC. 

From 25 patients, co-morbidity was unknown. 166 patients (23.3 %) were 

75 years or older. Patients less than 75 years had significantly less comorbidities 

than older patients (49 % vs. 64.5 % respectively; p=0.001). Of 

the 526 patients less than 75 years, co-morbidities were as follows: 278 (52.9 

%) 0, 188 (35.7 %) 1, 56 (11.4 %) 2 or more. No significant differences in 

the incidence of co-morbidities were observed between NSCLC and SCLC 

patients (52 % vs. 47 %; p=0.35). 332/711 (47 %) of the whole patient group 

was considered as ineligible for concurrent chemo-radiation (Figure 1). 

Conclusions: Nearly half of patients with stage III lung cancer were not eligible 

for concurrent chemo-radiation. Research to improve the prognosis of 

this group with alternative treatment strategies is needed.


894 poster 

OPTIMIZATION OF LUNG CANCER TREATMENT: A COMPARISON 

OF IMRT AND 3D-CRT 

R. Sjögren 1 , A. Haraldsson 1 , M. Karlsson 1 , P. Bergström 1 , P. Nilsson 1 

1 UMEÅ UNIVERSITY, Department of Radiation Sciences, Umeå, Sweden 

Purpose: Clinical experience shows a poor local tumor control for patients 

with inoperable non-small cell lung cancer (NSCLC) undergoing radiotherapy 

with or without chemotherapy. Concurrently, proof of a dose-response 

relationship is evident and modern techniques of radiotherapy such as IMRT 

have proven itself as a versatile treatment method. In this work we compare 

our current 3D-CRT technique with IMRT in a planning study. The aim is to 

increase the dose to tumor tissue but keeping the dose-volume constraints to 

normal tissue. 

Materials: Treatment plans for twenty-three NSCLC patients already treated 

at our department with 3D-CRT (2-5 coplanar beams) were renormalized to 

maximize the dose to PTV, with dose-volume constraints to normal tissue still 

below the limits used clinically. The IMRT plans were optimized to maximize 

the dose to GTV and PTV (74-732 cm3), allowing a heterogeneous dose 

in the PTV. The IMRT plans were optimized using seven 6 MV beams in a 

coplanar arrangement. Oncentra MasterPlan was used for the optimization. 

The method used for comparing our plans was D99, D1 and TCP. 

Results: D99 and D1 dose values of the GTV and PTV are presented in 

the figure as an average of the 23 patients. The dose values of the GTV are 

considerably higher in the IMRT case. Calculated TCP-values are also higher 

for the IMRT plans for all patients. 

Conclusions: IMRT is better than clinical 3D-CRT when comparing tumor 

control probability and allows, in an easy way, the possibility of giving an 

integrated boost to the GTV. 

895 poster 

OUTCOME OF LARGE V20 IN THE RADIOTHERAPY OF NSCLC 

O. Hansen 1 , C. Brink 2 , M. Nielsen 2 , K. H. Hansen 1 , P. Sørensen 1 

1 ODENSE UNIVERSITY HOSPITAL, Dept. of Oncology, R, Odense, Denmark 

2 ODENSE UNIVERSITY HOSPITAL, Radiophysic Laboratory, Dept. of 

Oncology, R , Odense, Denmark 

Purpose: High radiation dose to the lungs is associated with a worse outcome 

after radiotherapy (RT). The V20 the percentage of the lunge receiving 

a specific dose is used as a measure of the exposure of the lung to radiation. 

From 1995 to 2006 356 patients with non-small cell lung cancer received 3-D 

conformal RT with doses exciding 60 Gy in 30 fractions. According to the radiation 

protocols used a V20 up to 50% were allowed, and 79 patients (22%) 

had V20≥40%. We have retrospectively analysed the outcome of these patients. 

Materials: The patients were prospectively registered for RT dose, dose distribution 

to the lungs and the tumour, vital status and causes of death. Measurements 

of FEV1 and FVC were obtained for each follow-up. Information 

of side effects was retrospectively obtained from the patient files. 

Results: As of Feb. 2008 303 patients were dead, 247 due to lung cancer, 

14 of infection or treatment toxicity, and 42 due to courses not related 

to the cancer. In a univariate analysis the patients receiving V20 ≥40% had 

significant reduced survival compared with he patients receiving less the 3year 

survival being 6% and 31%, respectively. The number of death due to 

infection or treatment toxicity did not differ between the groups. In a Cox analysis 

it was still a statistical significant factor together with performance status 

(PS), GTV, and gender while age, FEV1 at start of RT, stage and history of 

smoking were not of significance. If the analyses were restricted to death 

not due to the cancer, PS, GTV, and V20 ≥40% were significant factors, but 

V20 ≥40% and GTV were still significant factors with PS being of borderline 

significance. If the analyses were restricted to patients surviving 2 years, the 

V20≥40% were still a significant factor for death and cancer death, but not 

death of other reasons. In logistic regression analyses the V20 together with 

poor pre-treatment FEV1 predicted occurrence of dyspnoe grade 3 during the 

first 3 months after radiation while other parameters were of no significance. 

V20≥40% did not influence a decrement in FEV1 and FVC obtained 3, 6, 

12, 24, 36, or 48 months after start of RT compared with the pre-treatment 

values. 

Conclusions: Large V20 is associated with poor survival but the excess 

death rate was caused by the cancer not toxicity. Large V20 was associated 

with occurrence of dyspnoe during the first 3 months, but did not influence 

measurement of FEV1 and FVC. 

896 poster 

OUTCOMES FOLLOWING EXTRAPLEURAL PNEUMONECTOMY 

AND EXTERNAL BEAM RADIOTHERAPY IN PATIENTS WITH 

MESOTHELIOMA. A SINGLE CENTRE EXPERIENCE 

G. Radhakrishna 1 , J. Adlard 1 , S. Wilson 2 , M. Snee 1 

1 

ST.JAMES’S INSTITUTE OF ONCOLOGY, Department of Non Surgical 

Oncology, Leeds, United Kingdom 

2 

ST.JAMES’S INSTITUTE OF ONCOLOGY, Medical Physics, Leeds, United 

Kingdom 

Purpose: Mesothelioma is an insidious disease arising from mesothelial surfaces. 

Median survival for mesothelioma is between 9 to 14 months and 

treatment options are limited. Early stage mesothelioma can be treated with 

a combination of Extra Pleural Pneumonectomy (EPP) followed by External 

Beam Radiotherapy (EBRT) however the morbidity may not justify this aggressive 

treatment. We reviewed patient outcome in terms of survival, pattern 

of relapse and time to relapse following EPP and EBRT treated in our centre. 

Materials: We reviewed the cases in our centre which had a combination of 

EPP and EBRT retrospectively using case notes and our planning system to 

calculate doses to the lung. Radiotherapy was delivered using 6MV photons 

with 3D conformal radiotherapy. We assessed the time to relapse and overall 

survival for our series. Although not carried out prospectively, we assessed 

acute and wherever possible late toxicities. 

Results: 15 patients were treated from1999 to 2005.12 patients had epithelial 

histological subtypes and 3 had a biphasic subtype. Patients were staged 

according to the AJCC TNM classification 2002. There were 4 patients with 

stage 1 disease, 3 patients with stage 2 disease, 5 with stage 3 disease and 

1 with stage 4 disease. 2 patients (including the patient with stage 4 disease) 

received pre operative chemotherapy. All but one of these patients received 

EBRT to a dose of 50Gy in 25 fractions with 6MV photons. One patient received 

a dose of 45Gy in 25 fractions.12 of the 15 patients relapsed within the 

abdominal cavity as their first site of relapse, and one patient relapsed with 

brain metastases but later developed abdominal relapse. The median interval 

to relapse following diagnosis was 15.9 months and the median time to death 

was 20.9 months. 14 patients died of mesothelioma and 1 died of treatment 

related gastro pleural-fistula (from a post mortem examination) as a consequence 

of both his surgery and EBRT. Of the 15 patients, 13 had evaluable 

dose plans. The lung DVH for the volume of contra lateral lung receiving less 

than or equal to 5Gy ranged between 0-42% with an average dose of 13.3 

and a median dose of 8 Gy. The most common toxicity acutely was nausea 

and lethargy. No grade 3 or 4 toxicities were noted in the acute setting. Two 

patients developed long term radiation toxicity with one patient developing hypertension 

due to radiation effects on her kidneys and one patient dying from 

a gastro-pleural fistula 

Conclusions: This data suggests that the time to relapse was approximately 

15.9 months and the commonest site of relapse was the abdomen. The median 

survival in our series was 20.9 months. The time to relapse and survival 

compares favourably with historical series. Most relapses occurred outside 

the thoracic cavity indicating effective local control using combined surgery 

and radiotherapy.

897 poster 

PATTERNS OF FAILURE AFTER COMBINED TREATMENT OF 

LIMITED DISEASE - SMALL CELL LUNG CANCER (LD-SCLC) 

M. Wierzchowski 1 , A. Sprawka 1 , L. Kepka 1 

1 MARIA SKLODOWSKA-CURIE MEMORIAL CANCER CENTRE AND INSTITUTE 

OF ONCOLOGY, Radiation Oncology, Warsaw, Poland 

Purpose: To review retrospectively patterns of failure after chemoradiotherapy 

in patients with LD-SCLC 

Materials: Between 1997 and 2006, 116 consecutive patients with LD-SCLC 

received 4 cycles of cisplatin and etoposide (PE) chemotherapy with sequential 

thoracic radiotherapy 28 x 2 Gy (70% ) or concurrent radiotherapy (CRT) 

(30%) 30 x 1,5 Gy in b.i.d. regimen given with first cycle of PE. 52% of patients 

were treated with 2D technique; the remaining 48% had conformal 3D 

radiotherapy. Radiation fields encompassed gross tumor with 1-2 cm margin 

and electively mediastinal lymph nodes. Supraclavicular regions were not 

electively treated. Prophylactic cranial irradiation (PCI) was administered to 

39% of patients. Local control was defined as a lack of radiological progression. 

Results: Median follow up for 11 living patients was 33 months. In-field local 

progression was observed in 41 patients (35%). Eight patients (7%) developed 

extra-field nodal recurrence (6/in supraclavicular, 2 /in mediastinum) including 

5 (4% of all) with isolated (without local progression) extra- field nodal 

recurrence in supraclavicular region. Distant recurrences occurred in 71 patients 

(61%); it is noteworthy to mention that 41 (35%) had brain metastases. 

There was statistically significant difference in cumulative Incidence of brain 

metastases with respect to the PCI use (50% vs. 16% at 2-years for no PCI 

vs. PCI group, p=0,003). The overall survival at 2 and 3 years were 36% and 

26%, respectively; median survival was 18 months. The overall survival at 

3 years was 21% for patients with sequential treatment, 33 % for those with 

CRT, p=0.18. There was no difference in 2-years overall survival with respect 

to the PCI use (39% PCI vs. 33% without PCI group, p=0.31).The diseasefree 

survival rates at 2 and 3 years were 17% and 13%, respectively. The 

cumulative incidence of local recurrences at 2 years was 48%. There was 

3% RTOG grade 3 or higher early radiation induced toxicity, 3% developed 

RTOG grade 3 late lung toxicity. 

Conclusions: Most common type of failure after treatment of LD-SCLC were 

distant metastases, second cause were local recurrences. Isolated extra field 

nodal failures were rare; however, the need for extension of elective fields to 

supraclavicular areas may be reconsidered in some patients. 

898 poster 

POST-OPERATIVE RADIOTHERAPY FOR LUNG CANCER: IM- 

PROVEMENT OF REGIONAL RECURRENCE-FREE SURVIVAL WITH 

THE USE OF 3D TECHNIQUE COMPARED TO 2D TECHNIQUE 

L. Masson-Côté 1 , C. Couture 2 , F. Harel 3 , A. Dagnault 1 

1 

L’HÔTEL-DIEU DE QUÉBEC DU CHUQ, Radiation Oncology, Québec, 

Canada 

2 

HÔPITAL LAVAL, INSTITUT DE CARDIOLOGIE ET DE PNEUMOLOGIE DE 

L’UNIVERSITÉ LAVAL, Department of Anatomopathology, Québec, Canada 

3 

CENTRE DE RECHERCHE DE L’HÔTEL-DIEU DE QUÉBEC DU CHUQ, 

Department of Biostatistics, Québec, Canada 

Purpose: The role of post-operative radiotherapy (PORT) in lung cancer 

treatment is controversial. Most studies on PORT were done with 2D ra- 


S 287 

diotherapy technique. However, modern 3D technique could improve PORT 

outcomes. 

Materials: A total of 172 charts of patients treated by PORT for lung cancer 

between 1995 and 2007 at L’Htel-Dieu de Quc were reviewed retrospectively. 

All patients underwent oncological resection of their tumour and were 

staged to rule out distant metastasis. Outcomes in terms of survival and 

secondary effects were analysed by comparing 2D technique (n=71) to 3D 

technique conformal radiotherapy (n=101). KaplanMeier survival curves were 

constructed and compared using log-rank test. Hazard ratios associated with 

3D technique were calculated with the use of multivariate Cox regression 

analysis controlling for age and smoking status. 

Results: Most tumours were NSCLC (85%). TNM stages included mostly 

stages IIB (23%), IIIA (49%) and IIIB (12%). Main clinical indications for 

PORT were positive resection margins (24%), stages pN2 (48%) and pN1 

(22%). All patients were treated with linear accelerator, 6MV or 23MV beams; 

the majority with a total dose of 50Gy, 2Gy per fraction. Treatment field was 

individually planned based on clinical indication and extent of resected disease. 

Most treatment fields included mediastinal lymph nodes and/or surgical 

bed. A minority of patients (25%) were treated with neoadjuvant or 

adjuvant chemotherapy. Patients treated with 2D technique were comparable 

to patients treated with 3D technique except for chemotherapy regimens and 

smoking status; there were more current smokers in the 2D technique group. 

Kaplan-Meier survival analysis showed 3D technique significantly improved 

regional recurrence-free survival (rRFS) compared with 2D technique (89% 

vs 70% at 4 years, p=0.0073); 3D technique was associated with a 3-fold decreased 

risk of rRFS (adjusted HR=0.34; 95% CI, 0.13-0.88; p=0.0258). Toxicities 

were acceptable with very few cases of radiation-induced pneumonitis 

(5%), grade 3 dysphagia (0.6%) without grade 4 dysphagia. Side effects were 

comparable for both groups. 

Conclusions: 3D technique conformal radiotherapy in PORT for lung cancer 

improves regional recurrence-free survival of patients compared to 2D technique. 

Better control of mediastinal lymph nodes with the 3D technique best 

explains our results. 

899 poster 

PRELIMINARY RESULTS FROM A PHASE 1 DOSE ESCALATION 

TRIAL OF LIMITED FIELD HYPOFRACTIONATED THORACIC RA- 

DIOTHERAPY FOR LIMITED STAGE SMALL CELL LUNG CANCER 

W. H. Y. Roa 1 , Q. Chu 2 , C. Butts 2 , A. Joy 2 , D. Fenton 2 , M. Smylie 2 , A. 

Reiman 2 , D. Yee 1 

1 CROSS CANCER INSTITUTE, Radiation Oncology, Edmonton, Canada 

2 CROSS CANCER INSTITUTE, Medical Oncology, Edmonton, Canada 

Purpose: Though thoracic radiotherapy (RT) has an established role in combined 

modality management of limited stage small cell lung cancer, the optimal 

RT dose-fractionation regimen remains undefined. Recent evidence 

indicates intensification of RT dose and minimisation of overall RT treatment 

time improve local control and overall survival for limited stage small cell lung 

cancer patients. Hypofractionation is a strategy which may help achieve both 

goals of dose escalation without prolonging overall treatment time. The purpose 

of this study is to define the maximal tolerated dose of hypofractionated 

thoracic RT combined with chemotherapy for limited stage small cell lung 

cancer. 

Materials: Patients were accrued to one of four RT dose levels: 54 Gy, 58 

Gy, 62 Gy or 65 Gy. RT was given in 25 daily fractions and given concurrently 

with the earliest chemotherapy cycle logistically possible. Six patients were 

sequentially accrued to each dose level based on observed RT-related acute 

toxicity rates in each dose level. RT was planned using conformal techniques 

and targetted gross disease (visible lung tumor and involved nodes) plus margin. 

All patients received 4 cycles of concurrent platinum-based chemotherapy. 

Disease response was assessed 4-6 weeks after chemoRT completion 

and complete/ near complete responders were offered prophylactic cranial 

irradiation. The maximal tolerated RT dose was based on the dose which 

caused unacceptably high RT-related toxicity rates. Patients were regularly 

assessed before, during and after RT completion for treatment-related toxicities 

and disease status. Toxicity was graded using NCI Common Toxicity 

Criteria scales. 

Results: Twelve limited stage patients have been accrued. Dose level one 

(54 Gy) has been closed and six patients have been accrued to dose level 

two (58 Gy). All 6 patients prescribed 54 Gy and 3 patients prescribed 58 

Gy have completed all prescribed RT. There have been no treatment-related 

deaths. The maximum acute RT toxicity has been grade 2 esophagitis which 

occured in 3 patients receiving 54 Gy and one receiving 58 Gy. There have 

been 3 hospitalizations (2 febrile neutropenia and 1 ruptured duodenal ulcer). 

Of 5 patients who have been re-staged, 4 have attained complete responses. 

Five patients have received PCI. There have been no disease progression/ 

recurrence events so far. 

Conclusions: RT has been well-tolerated and the maximal tolerated hypofractionated 

thoracic RT dose has not yet been determined on this protocol.


900 poster 

PRELIMINARY RESULTS OF AN INTERNATIONAL MULTI-MODALITY 

IN-SILICO TRIAL FOR LUNG CANCER 

S. Qamhiyeh 1 , C. Rasch 2 , M. Pijls-Johannesma 3 , M. Engelsman 4 , D. De 

Ruysscher 3 , A. Dekker 3 , P. Lambin 3 

1 

DEUTSCHES KREBSFORSCHUNGSZENTRUM (DKFZ), Radiation Oncology, 


2 

NETHERLANDS CANCER INSTITUTE (NKI), Radiation Oncology, Amsterdam, 

Netherlands 

3 

MAASTRICHT RADIATION ONCOLOGY (MAASTRO), GROW RESEARCH 

INSTITUTE, UNIVERSITY HOS, Radiation Oncology, Maastricht, Netherlands 

4 



Purpose: To report on the preliminary results of our multi-centric "in-silico 

trial" for radiotherapy for lung cancer. 

Materials: During the first phase of our international study multiple treatment 

plans will be designed for each of twenty-five lung cancer patients. A wide 

variety of external beam radiotherapy techniques and modalities will be used; 

protons and carbon ions (both passive scattered and IMPT), and photons 

(conformal, IMRT, Tomotherapy). Typically, each planning technique is applied 

by a different institute. The study will assess the benefit of using each 

modality and delivery technique only, assuming, e.g., uniform patient setup 

accuracy, breathing motion and fractionation schedules. 

Results: We will discuss the planning protocol that was agreed upon. This 

includes inclusion criteria, the desired target coverage, the priority and dosevolume 

limits of organs at risk. CT-scans, delineated targets and normal tissues 

have recently been made available to each of the participating institutes. 

Submitted treatment planning data for three patients currently only allows a 

comparison between IMRT and passive-scattered protons. The IMRT plans 

for two patients did not fulfill the criterion that only 2 % of the PTV was allowed 

to receive more than 107 % of the prescribed dose. All proton and IMRT plans 

stayed within the dose limits for lung, oesophagus and heart. The mean dose 

to the oesophagus was, averaged over all three patients, 11.4 Gy for IMRT 

and 7.3 Gy for protons. For the heart these values are 4.0 Gy and 0.1 Gy, 

respectively. The lung was the primary organ at risk to spare during treatment 

planning. The mean lung dose decreased from 12.8 Gy for IMRT to 8.6 Gy 

for protons with both plans ensuring target coverage under setup errors and 

breathing motion. 

Conclusions: The technical hurdles for our study have been overcome and 

treatment planning data is being gathered from all participating centers. We 

hope that the completed study will provide an indication regarding the possible 

benefit of particle therapy. The preliminary results demonstrate a significant 

reduction of mean lung dose by more then 25 %, which gives the 

opportunity of dose escalation at an isotoxic level. 

901 poster 

PROSPECTIVE OBSERVATIONAL CLINICAL STUDY EVALUATING 

THE EFFICIENCY AND TOXICITY OF HEMITHORACIC RADIOTHER- 

APY AFTER EXTRA PLEURAL PNEUMONECTOMY IN MALIGN 

PLEURAL MESOTHELIOMA 

F. Akyol 1 , P. Hurmuz 1 , G. Ozyigit 1 , U. Selek 1 , S. Emri 2 

1 



2 

HACETTEPE UNIVERSITY, FACULTY OF MEDICINE, Chest Diseases, 


Purpose: To evaluate the efficiency and the toxicity of three dimensional 

conformal hemithoracic radiotherapy (3D-HTCRT) after extra pleural pneumonectomy 

(EPP). 

Materials: In this prospective study between September 2004 and June 

2007, 14 patients (4 female, 10 male) referred to our department for 3D- 

HTCRT after EPP were assessed. During EPP operation ipsilateral lung 

was removed together with parietal pleura, visceral pleura, pericardium and 

hemidiaphragm, then diaphragm and pericardium were reconstructed. Radiotherapy 

(XRT) with 1.8 Gy daily fraction doses to a total dose of 50.4 Gy 

was applied to hemithoracic cavity. 

Results: The median age was 51 years (range, 3361 years), and 12 patients 

(86%) had white stucco history. The disease was left sided in 8 cases and 

right sided in 6 cases. Most commonly seen histopathology was epitheliod 

type (79%). According to American Joint Commission on Cancer (AJCC) 

2002 staging system one case was stage I, 4 cases were stage II, 9 cases 

were stage III. A total median dose of 50,4 Gy XRT with 1,8 Gy daily fraction 

doses was applied to hemithoracic cavity. Eleven patients received adjuvant 

chemotherapy consisting of cisplatin and pemetrexed combination. After a 

median of 16 months follow-up, intrathoracic control was 100%. Eight patients 

developed abdominal relapse and 2 developed distant metastasis. Ten 

cases were dead. Two of them were without the evidence of disease. Median 

2-year overall and disease free survival rates were 25% and 21%. XRT 

was generally well tolerated. The acute toxicities of XRT were grade I-II and 

did not cause a treatment cessation. In one case, XRT was stopped due to 

emphyema secondary to surgery. In one patient the etiology of the ascites 

developed during the treatment was established to be pericarditis. 

Conclusions: Excellent intrathoracic control with 3D-HTCRT after EPP 

seems to change the relapse patterns of MPM. High rates of relapses in the 

abdomen may be prevented by preoperative assessment of the abdomen with 

invasive procedures like laparoscopy plus peritoneal fluid cytology and paying 

high attention to avoid tumor spillage during the surgery. More effective 

systemic treatment may be needed to prevent the recurrences outside the 

thorax. 

902 poster 

PROSPECTIVE STUDY ON QUALITY OF LIFE IN EARLY-STAGE 

NON-SMALL CELL LUNG CANCER PATIENTS TREATED WITH 

4-DIMENSIONAL STEREOTACTIC RADIOTHERAPY. 

N. van der Voort van Zyp 1 , J. B. Prévost 1 , C. Braat 1 , J. Praag 1 , P. 

Levendag 1 , J. Nuyttens 1 

1 ERASMUS MC- DANIEL DEN HOED CANCER CENTER, Radiotherapy, 


Purpose: To assess the impact of 4-dimensional stereotactic radiotherapy 

(4-D SRT) on the patient’s quality of life (QoL). 

Materials: From January 2006 to December 2007, 38 patients with pathologically 

confirmed T1-2N0M0 non-small cell lung cancer were treated with 4-D 

SRT using Cyberknife. Treatment consisted of 60 Gy in 3 fractions for 30 patients 

with peripheral tumors and 45-50 Gy in 3-5 fractions for 8 patients with 

central tumors. Thirty-four patients were medically inoperable and 4 refused 

surgery. Seventeen patients had a T1 tumor and 21 had a T2 tumor. The majority 

of patients were male (81.6%). The median age was 77.3 years (range: 

55-87 yrs). Nineteen patients had a charlson comorbidity score ≤1, twelve 

a score of 3-4 and six a score ≥5. The median cumulative illness ranking 

score was 6. The EORTC Quality of Life Questionnaire QLQ-C30 and the 

EORTC QLQ-LC 13 were used to investigate changes in QoL. Assessments 

were performed before treatment, at 3 weeks, and at 2, 4, 6, and 9 months 

after treatment until death or progressive disease. 

Results: The median follow up was 9 months (range: 1-21 months). Compliance 

was 89.5% (34/38) at 3 weeks, 94.4% (34/36) at 2 months, 97% (32/33) 

at 4 months, 100% (27/27) at 6 months and 94.7% (18/19) at 9 months. Three 

patients had progressive disease and were excluded from analysis at 2, 4 and 

9 months. Six patients died, three at 6 months and three at 9 months. The 

emotional functioning score showed a significant improvement at 3 weeks 

until 4 months. Global health status showed a trend toward improvement at 

9 months (p=0.068). All other functional scores including global health status, 

performance, cognitive, social and role functioning showed no significant 

changes. Respiratory symptoms showed no significant changes after radiotherapy 

although a trend was seen for an increase in chest pain at 3 weeks 

(p=0.057) and an increase in dyspnoe at 6 months (p=0.053). During and 

after therapy no significant increase in general symptoms was seen except 

for a slight increase in loss of appetite at 2 months (p=0.03). 

Conclusions: Four-dimensional stereotactic radiotherapy showed a significant 

increase in the emotional functioning score from 3 weeks until 4 months 

after treatment and a trend for increased global health score at 9 months after 

treatment. Remaining functional scores, respiratory and general symptoms 

showed no significant changes, suggesting that 4D-SRT was well tolerated in 

this patient group. 

903 poster 

RADIATION THERAPY OF NON-SMALL CELL LUNG CANCER WITH 

DOSE ESCALATION ON COBALT 60 GAMMA UNITS. 

V. Sotnikov 1 , V. Kharchenko 1 , G. Panshin 1 , E. Nikolaeva 1 , A. Ivashin 1 , 

O. Scvortsova 2 

1 RUSSIAN SCIENTIFIC CENTRE OF ROENTGENORADIOLOGY, Radiation 

Therapy, Moscow, Russian Federation 

2 RUSSIAN SCIENTIFIC CENTRE OF ROENTGENORADIOLOGY, Laboratory, 

Moscow, Russian Federation 

Purpose: The high dose radiation therapy is used in numerous tumor sites, 

including lung. It demands expansive modern equipment and never realized 

on Cobalt 60 gamma units. The purpose of this work was to evaluate the 

toxicity and shot term results of telegamma therapy of peripheral non-small 

cell lung cancer (NSCLC) with escalation of daily dose (3Gy) and total dose 

60Gy. 

Materials: Between January 2003 and September 2007 we intend to treat 33 

patients age 45-81 years (median age 68) with peripheral NSCLC (T1-4N0- 

3M0-1, stage IA-3, stage IB-9, IIB-6, IIIA-4, IIIB-5, stage IV -4 pa-tients), not 

suitable for surgery due to stage or severe cardiac and/or lung comorbidities. 

Eleven patients received 2-4 cycles of neoadjuvant chemotherapy After CTbased 

2-D planning all the patients were irradiated on Cobalt 60 gamma units. 

Tumor and involved lymph nodes irradiated separately. The tumor motion was 

determined by roentgenoscopy on simulator. Gross tumor volume + 1cm of 

surrounding lung tissue were included in PTV. In order to minimize MLD two 

fields with wedges were typically used as in the most of the cases the tumor 

was located near the chest wall or directly invade it. The daily dose 3Gy

(specified at 90% isodose) was given 5 times a week. The total dose for 

tumor was 60Gy (α/β=3, EQD2=72Gy, M.Joiner equation), the total dose for 

involved lymph nodes was 39Gy (EQD2=47Gy). 

Results: 31 (93%) patients completed the full course of irradiation and were 

included in analysis. In two cases the irradiation was finished prematurely 

due to exacerbation of ischemic heart disease. In 6 cases the irradiation was 

in-terrupted due to esophagitis. According to RESIST criteria, after the radiation 

therapy the complete regression of the tumor was seen in 7 patients 

(23%), partial regression of the tumor was seen in 14 patients (45%), stabilization 

in 10 patients (32%). Pulmonitis grade II was diagnosed only in 

7 patients (23%) during the next 3 months after the radiation therapy and in 

all cases resolved successfully. Local changes of lung tissue density were 

revealed radiologically in all patients. No patients experienced shot-term or 

long-term toxicity grade 3-4 according to RTOG criteria. Disease-specific survival: 

1 year -91,1%, 2 years 46,7%, 3 years 35,0%. Survival without infield 

progression: 1 year 84,0%, 2 years 53,8%, 3 years 53,8%. Overall survival: 

1 year 80,7%, 2 years 39,0%, 3 years 29,3%. 

Conclusions: Radiation therapy of the peripheral non-small cell lung cancer 

with escalation of daily dose up to 3Gy (60Gy total dose) can be safely 

performed on traditional Cobalt 60 gamma units. Comparing with classic fractionation 

this regimen decrease the period of irradiation from 40 to 28 days, 

and the number of procedures from 30 to 20, so more patients can be treated 

on the same equipment with more chances for local cure. 

904 poster 

RADIATION-INDUCED CHANGES IN POSITRON EMISSION TO- 

MOGRAPHY OF IRRADIATED LUNGS IN ESOPHAGEAL CANCER 

PATIENTS TREATED WITH RADIOTHERAPY 

H. Yoon 1 , I. Lee 1 , Y. Kim 1 , J. Kim 1 , D. Lee 1 , C. Lee 1 , K. Keum 1 , M. Yun 

2 , H. Cho 2 

1 

YONSEI CANCER CENTER, Department of Radiation Oncology, Seoul, 


2 

YONSEI CANCER CENTER, Department of Nuclear Medicine, Seoul, Korea 

Republic of 

Purpose: To evaluate patterns of fluorodeoxyglucose (FDG) uptake of the 

irradiated lung after completing radiotherapy in esophageal cancer patients. 

Materials: From May 2005 to June 2007, a total of 35 patients with 

esophageal cancer received 3-dimensional conformal radiotherapy. The 

mean age was 64.1 years, and the mean radiation dose was 59.6 Gy. The 

percentages of lung volume receiving at least 10 Gy (V10) and 20 Gy (V20) 

were recorded from each pulmonary dose–volume histogram. Follow up 

Positron Emission Tomography (PET) was conducted from 2 weeks to 7 

months after radiotherapy. The maximum standard uptake value (SUV) was 

evaluated in the irradiated lungs. The subsequent PET study was performed 

after radiotherapy in 16 patients. 

Results: No instances of severe radiation pneumonitis were detected in the 

35 patients receiving a mean lung dose of less than 12 Gy and less than 20% 

occurrence was detected in patients receiving a mean dose of V20. FDG uptake 

was positive (SUV = 3.95 b 1.9) in 12 patients (34.3%). The positive FDG 

uptake in the irradiated lung varied according to the time of the PET evaluation. 

Early evaluation (< 3 months) of PET demonstrated increased FDG 

uptake in the irradiated lung (58.3%) as compared to delayed evaluation (≥ 

3 months) of FDG uptake (21.7%). Among the patients who underwent sequential 

PET, eight patients (50%) exhibited Increased FDG uptake in the first 

follow-up PET. At the second follow-up PET, the FDG uptake was negative in 

all patients that showed increased FDG uptake in first follow-up PET. 

Conclusions: This study demonstrated various patterns of increased lung 

metabolic activity in the irradiated lung relative to the period of time between 

radiotherapy and sequential PET scanning. PET scanning of irradiated lungs 

may be useful in monitoring patients receiving radiation therapy for thoracic 

malignancies and may have a predictive value for pulmonary toxicity and subsequent 

fibrosis. 

905 poster 

RADIOBIOLOGICAL AND ISODOSE-BASED METHODOLOGY FOR 

OPTIMIZING THORACIC HYPOFRACTIONATED RADIOTHERAPY 

H. Gay 1 , C. Sibata 1 , R. Allison 1 , B. Jeremic 2 

1 THE BRODY SCHOOL OF MEDICINE LEO JENKINS CANCER CE, Department 

of Radiation Oncology, Greenville, North Carolina, USA 

2 INTERNATIONAL ATOMIC ENERGY AGENCY, 12345, Vienna, Austria 

Purpose: Define potential normal tissue dose constraints to minimize the 

mortality and morbidity of hypofractionated lung radiotherapy. 

Materials: This radiobiological analysis assumes that: the linear quadratic 

(LQ) model is valid up to 28 Gy per fraction, the α/β ratio is 2 for the spinal 

cord and brachial plexus, 4 for pneumonitis, 10 for acute skin reactions, and 

3 for late complications in other normal tissues. A review of the literature 

was made to generate possible normal tissue constraints for the organs at 

risk from hypofractionated lung radiotherapy, and serve as the basis for the 

radiobiological and isodose-based analysis. 


S 289 

Results: Preliminary normal tissue constraints to reduce mortality and morbidity 

were defined for most organs at risk from hypofractionated lung radiotherapy. 

A modified dose nomenclature was introduced to facilitate the 

comparison of hypofractionated doses. Potential side effects from hypofractionated 

lung radiotherapy such as aortic dissection, neuropathy, and fatal 

organ perforation rarely seen in conventional treatments were identified. The 

isodose-based method for treatment plan analysis and normal tissue dose 

constraint simplification was illustrated. 

Conclusions: The radiobiological analysis based on the LQ method, biologically 

equivalent dose nomenclature, and isodose-based method proposed 

in this study to simplify normal tissue dose constraints and treatment plan 

evaluation may also be applied to extrathoracic hypofractionated radiotherapy. 

Prospective validation of the preliminary normal tissue dose constraints 

obtained for hypofractionated lung radiotherapy is necessary. 

906 poster 

RESPIRATORY FUNCTION MONITORING IN RADIOTHERAPY OF 

LUNG CANCER PATIENTS 

A. Benko 1 , J. Hadjiev 1 , M. Vallyon 1 , C. Glavak 1 , P. Bogner 1 , I. Repa 1 

1 UNIVERSITY OF KAPOSVAR HEALTH CENTRE, Department of Oncoradiol- 

ogy, Kaposvar, Hungary 

Purpose: Since February 2006 selected lung cancer patients have been 

monitored during irradiation with a piston PDD 301/S spirometer unit. This 

study was designed for monitoring differences in FEF1/FVC before and after 

irradiation. 

Materials: Eleven Stage IIb-IV patients were enrolled in the study. The mean 

age was 59.8 years, with lung cancer Karnofsky performance status higher 

than 70%. 55% of the tumors were located in the upper lobe, 27% in the 

lower lobe and 18% of them were central. All patients received CT based 

3D conformal irradiation with 1,8 Gy fractions daily, that is an overall mean 

dose of 50-60 Gy. FEV1 and FEV1/FVC were measured before and after the 

treatment. DVH based analysis was also performed in order to see to what 

extent had the right or left lung received 10 Gy and to what extent they had 

been irradiated by 20 Gy. 

Results: The mean lung volume receiving 10 Gy was 63% in the left and 85% 

in the right lung. Mean lung volume receiving 20 Gy was 67% (left lung) and 

13 % (right lung). The mean change in FEV1 improved after the treatment. 

Changes in FEV1/FVC were only moderateby the end of the treatment but 

data on both parameters were valuable. 

Conclusions: Respiratory function monitoring is a safe and patient-friendly 

method both in terms of administration as well as conduction during and after 

radiation therapy. It can be employed freely several times during an irradiation 

treatment to gather objective data on the patients’ subjective feeling of respiratory 

obstruction. It presents valuable information on possible side effects 

of the treatment, too. Our study showed that no significant changes were 

measured in FEVC1 and FEV1/FVC. It proves that the use of CT based 3D 

conformal radiation thearpy is a tolarable and safe method for the treatment 

of lung cancer patients. 

907 poster 

ROBOTIC STEREOTACTIC RADIOSURGERY USING A GENERA- 

TION 4 CYBERKNIFE R○ FOR PRIMARY AND METASTATIC LUNG 

TUMORS: A PRELIMINARY REPORT 

W. K. Chung 1 , S. J. Sim 1 , C. K. Min 1 , G. J. Kim 1 , J. W. Son 2 

1 

KONYANG UNIVERSITY HOSPITAL, Radiation Oncology, DaeJeon, Korea 

Republic of 

2 

KONYANG UNIVERSITY HOSPITAL, Pneumology, DaeJeon, Korea Republic 

of 

Purpose: In this study, we evaluated the clinical response to and complications 

from robotic stereotactic radiosurgery with a Generation 4 (G4) 

CyberKnife R○(Accuray Incorporated, Sunnyvale, California, USA) for the 

treatment of primary and metastatic lung cancer. 

Materials: We analyzed 21 patients (13 men and 8 women) between the 

ages of 29 to 81(median 64) with 22 intrathoracic lesions diagnosed pathologically 

in our hospital or at other hospitals. Fifteen tumors were primary, 3 

colorectal, 1 from breast cancer and 2 were Sarcomas. ECOG performance 

scores were generally favorable. Three to 4 fiducial markers were implanted 

in or around the tumors for each patient before the recording of their planning 

CT studies. Gross tumor volume (GTV) ranged between 2 cc and 426 cc 

(median 36.2 cc). The planning treatment volume (PTV) included the GTV 

plus a 3- to 5-mm margin. A dose of 24 Gy to 60 Gy (median 50 Gy) was 

prescribed to the 64% to 89% isodose line (median 74%) and delivered in 

3-4 fractions. Synchrony R○Respiratory Tracking System (Accuray) was used 

during the treatment as the patient breathed freely. Median follow-up period 

was 7 months. Clinical outcomes were evaluated by chest CT and PET-CT 

every 3 months after the treatment. 

Results: All patients were evaluable for response and complications. Eight 

patients experienced a complete response (38%), 11 partial response (52%) 

and 2 patients’ disease progressed (10%). We observed 3 grade I-II radia-


tion pneumonitis (13%), and 4 cases of pneumothorax (19%) due to fiducial 

placement. One patient, who had undergone conventional radiation therapy 

of 66 Gy in 33 fractions before 3 months receiving 24 Gy in 3 fractions as a 

boost to a residual lesion in the right hilar region, experienced active bleeding 

at the target site and was lost. 

Conclusions: Robotic stereotactic radiosurgery with CyberKnife is a feasible 

treatment option with an acceptable complication rate. However, special attention 

must be paid to central lesions and repeat treatments of lung lesions. 

908 poster 

ROBOTIC STEREOTACTIC RADIOTHERAPY FOR LUNG TUMOR: 

DOSE AND TOXICITY EVALUATION. 

G. A. Panizzoni 1 , G. Bolzicco 1 , C. Baiocchi 1 , A. Testolin 1 , C. Mari 1 , M. S. 

Favretto 1 , F. Messina 1 , P. Scalchi 2 , C. Cavedon 2 , S. Cora 2 , F. Colombo 

3 , P. Francescon 2 , R. Guglielmi 1 

1 S. BORTOLO HOSPITAL, Radiation Oncology, Vicenza, Italy 

2 S. BORTOLO HOSPITAL, Medical Physics, Vicenza, Italy 

3 S. BORTOLO HOSPITAL, Robotic Radiosurgery Unit, Vicenza, Italy 

Purpose: 87 consecutives lung tumors, 33 early stage cancer, 39 solitary 

lung metastases and 15 local relapses after traditional treatments, were evaluated 

to report local recurrence rate and treatment tolerance after Robotic 

Stereotactic Radiotherapy with Cyberknife (Accuray) at St. Bortolo’s Hospital 

of Vicenza, Italy. 

Materials: The median age was 69 (range 31-86). Doses ranged from 26 Gy 

in one single fraction to 36 Gy in three consecutive days. Peripheral tumors 

were implanted with gold fiducials. The doses were correlated to site, volume 

and previous external beam irradiations. The dose to the PTV was prescribed 

to the 77-80 % isodose line. The median follow-up was 9 months (range 4- 

26). 

Results: No major toxicity was experienced: mild lung fibrosis in 26/87, disphagia 

in one case. The response was evaluated with a CT or CT-PET 8 

weeks after the last treatment day and routinely thereafter. Local control 

(CR+PR+NC) was different and correlated to clinical presentation (primary: 

21/33, metastatic: 16/39, relapses: 11/15) to dose (26 Gy in one fraction: 

20/39, fractionated 36 Gy: 28/48), to the volume (less than 10 cmc: 25/38, 

more than 10 cmc: 24/49). 

Conclusions: Local control appears of 65% if the lesion is smaller than 10 

cmc, peripheral and without previous EBRT. For further presentations, to improve 

our results, we consider that is necessary to reach higher doses with a 

larger number of fractions. 

909 poster 

SHIFT INVARIANCE OF THE DOSE DISTRIBUTION FOR ONLINE 

CORRECTIONS OF STEREOTACTIC BODY RADIOTHERAPY OF 


M. Temurhan 1 , J. J. Sonke 1 , G. Borst 1 , J. Belderbos 1 , E. Damen 1 



Purpose: Substantial baseline variation (motion of the mean tumor position 

relative to the bony anatomy) has been observed in lung cancer patients 

treated with stereotactic body radiotherapy (SBRT). Therefore, online corrections 

based on the actual tumor position are used in our institution. This 

procedure assumes shift invariance of the dose distribution for small corrections. 

In this planning study the maximum shifting distance was determined 

beyond which the plan should be re-planned before treatment. 

Materials: The treatment plans of five lung cancer patients treated with 

SBRT (3x18 Gy) were taken and recalculated (Pinnacle 7.6c) after shifting 

the isocenter and the planning target volume (PTV), without re-optimizing. 

Shifts (0.5 cm, 1.0 cm and 1.5 cm) were applied in 12 equiangular spaced 

directions of the sagittal plane (baseline shifts are small in the left-right direction).For 

the five patients, the number of beams varied from 13 to 16, their 

directions depending on the position of the tumor. PTV volumes ranged from 

13.5 cc to 86.9 cc. The main objective for the original plans was that at least 

95% of the PTV volume received 54 Gy. For this study the following was 

recorded for each shift in each plan:- the fraction of the PTV receiving 54 Gy 

(V54),- the minimum dose received by 95% of the PTV (D95). 

Results: The results are summarized in table 1. As expected, increasing 

shifts led to increasing deterioration of the PTV coverage, but varied over the 

patient group. Typically, D95 dropped up to 1 Gy for 0.5 cm shifts, 1-2 Gy for 

1.0 cm shifts and 1-3 Gy for 1.5 cm shifts. Patient 5 is an exception, manifesting 

a large deterioration of the dose distribution already at small shifts, which 

was tracked down to an extremely low density of the lung tissue surrounding 

the tumor (

it is often difficult to perform a re-operation for these patients due to their 

medical complication or high age. We retrospectively evaluated the feasibility 

and effect of stereotactic body radiotherapy (SBRT) to a growing solitary lung 

tumor after curative surgery for NSCLC. 

Materials: Twenty-one patients presented with a solitary lung tumor after curative 

surgery for NSCLC were treated with SBRT from December 2000 to 

May 2007. All the patients were medically inoperable. The median age was 

75 years old (range; 56-80 years old). The histologic type was adenocarcinoma 

in 6 tumors, squamous cell carcinoma in 2, large cell carcinoma in 

1, and unknown in 12. The tumors without pathologic confirmation of malignancy 

were diagnosed by the continuous growing on the computed tomography 

examinations and18F-fluorodeoxyglucose positron emission tomography 

positive lesions. All tumors were less than 3 cm. SBRT was performed using 

on-board kilo-voltage X-ray imaging system. The prescribed doses were 45 

Gy / 3 fractions in 4 patients, 48 Gy / 4 fractions in 6, 60 Gy / 8 fractions in 7, 

and 60 Gy / 15 fractions in 4. 

Results: All the patients tolerated SBRT very well. The median follow-up 

period from the time of completion of SBRT was 28.9 months (range; 6.1- 

46.2 months). Acute adverse events were graded using the National Cancer 

Institute’s Common Toxicity Criteria for adverse events version 3.0. Grade 1 

acute pneumonitis developed in 17 patients, grade 2 in 3 patients, and grade 3 

in 1 patient. One patient did not develop radiation-induced pneumonitis. Late 

lung toxicity at one year after SBRT was acceptable. Twenty of 21 tumors 

were locally controlled during the follow-up period. The 3-year local control 

probability was 100 %. The disease-free, cause-specific, and overall survival 

rates at 3 years after SBRT were 58.3 %, 100 %, and 94.7 %, respectively. 

Conclusions: SBRT is well tolerated in patients with some co-morbidity, and 

high local control probabilities and minimal toxicity can be achieved. SBRT 

should be considered as a choice of treatment for patients with a solitary lung 

tumor after curative surgery for NSCLC. 

912 poster 

STEREOTACTIC TREATMENT OF LUNG MALIGNANCIES GUIDED 

BY CONE-BEAM CT 

F. Casamassima 1 , L. Masi 1 , C. Polli 1 , I. Bonucci 1 , C. Menichelli 1 , E. 

D’Imporzano 1 

1 U.O.RADIOBIOLOGIA CLINICA UNIVERSITÀ DI FIRENZE, Fisiopatologia 

Clinica, Firenze, Italy 

Purpose: We analyzed the accuracy, safety and efficacy of hypofractionated 

(1-3 fx) treatment for lung malignancies using CBCT for target alignment without 

any external frame. 

Materials: 131 patients were treated for 202 lesions (47 primary and 155 

metastases). Median age was 69 yars. Lesions centrally located were 49. 

Median diameter of target was 2.6 cm (range 0.5-6 cm). The GTVs was delineated 

on two CT data sets at the end of inspiration and expiration to obtain 

an ITV (median volume was 20.6cc, range 1 to 200cc). The patients were 

trained to reduce and visually chek their breathing volume using a computerized 

spirometer (ABC Elekta). The dose for peripheral lesions was 26 Gy 

in single fraction and was 30 Gy in 3 fx for centrally located. The dose was 

prescribed at isocenter. Median BED 10 value was 83 Gy. Dose constraints 

for OAR was defined according to RTOG criteria. Treatment was delivered 

by 6 Mv Linac using multiple arcs and dynamic mMLC. CBCT (Elekta Synergy) 

was recorded before each fx and matched on planning CT (Elekta XVI) 

to ensure the alignment of the target inside the ITV contours. For response 

evaluation RECIST criteria was used. CT scans were recorded 60 days after 

the end of treatment and every 3 months successively. Any acute or delayed 

toxicity was recorded according to WHO criteria. 

Results: Local response to treatment in 174 evaluable Pts. was: 34% CR, 

29% PR, 26% SD, 11% PD respectively. Complete response, separately 

analysed for BED values, statistically correlates with BED10 (p. 0.009): CR 

21% and 44% for BED10 inferior or superior to 90 Gy respectively Median 

OS for all Pts was 16.4 months. No statistically significant difference between 

primary or metastatic lesions was found. On the contrary a difference on OS 

(p. 0.05) was found between pts treated by BED10 < or > to 90 Gy and for 

lesions volume less than 30 cc (p. 0.012). PFS was 70% at 16.6 months 

(median not reached). NSCLC Pts treated by a single fx showed better OS 

(p. 0.05). 98 pts are still alive and only 3 out of 33 died for progressive disease 

in the lung. The acute reactions in the lung, evaluable on CT scan, were 

observed only in 58% of emphysematous pts. v/s 70% of other Pts. These 

radiological acute and late reactions were not symptomatic, except for a mild 

cough. 

Conclusions: In our experience the SRS/T of lung malignancies appear safe 

and effective. Local control and OS correlates with BED10 values of treatment 

and whit the volume ( 30 cc) of lesion. The single shoot treatment 

appears more effective (p.0,05) for NSCLC pts. Lungs emphysema leads to 

minor local reactions. Since the lesions are well recognizable on CBCT its 

use assures a safe reduction of ITV particularly when the pts were trained to 

reduce their breathing volume by ABC. 

913 poster 


S 291 

THE RISK OF THE ACUTE SIDE EFFECTS IN THE LUNG AFTER 

3-DIMENSIONAL - CONFORMAL RADIOTHERAPY FOR NON-SMALL 

CELL LUNG CANCER 

M. Spych 1 , J. Fijuth 1 

1 MEDICAL UNIVERSITY OF LODZ, Radiotherapy, Lodz, Poland 

Purpose: To evaluate the risk of acute side effects in the lung after 3D-CRT 

in patients treated for non small cell lung cancer (NSCLC). Attempt of singling 

out clinical factors and factors related to treatment technique which may 

increase the risk of the acute postradiation pneumonitis. 

Materials: The analysis concerned 34 consecutive patients who underwent 

radical radiation therapy for NSCLC. The endpoint for this analysis 

was the occurrence of Grade 2 radiation pneumonitis according to modified 

RTOG/EORTC toxicity score. Clinical factors as well as factors related to 

treatment techniqes were included to the statystical analysis. The Kaplan 

Meier estimator was used to evaluate the risk of radiation pulmonitis development 

in analysed patients group. A variance analysis was used, to find 

the impact of dosimetric factors on toxicity intensification. Finally, univariate 

and multivariate analysis was carried through, to single out factor which could 

describe the toxicity risk in the most precise way. 

Results: Fifty three percent of patients included to the study suffered from 

acute postradiological pneumonitis. Fifteen patients (44,1%) experienced 

grade 2, and the next three patients (8,9%) grade 3 toxicity in modyfied 

RTOG/EORTC scale. No Grade 4 was recorded in this study. Clinical factors 

did not have any impact on the risk of acute lung toxicity (p≥0,18). The analysis 

of dose-volume histograms showed a difference in lung volumes reciving 

low doses (10 Gy, 20 Gy) in groups of patient with and without clinical manifestation 

of the side effect (p0,01). In lung volumes receiving the dose of 40 

Gy, 50 Gy and 60 Gy, which were defined as high dose lung volumes, the statistically 

significant differences were noticed in total lung volumes (p≤0,002). 

Results of variance analysis indicated the relationship between the percentage 

of lung volume receiving low dose of the ionizing radiation, and the course 

of acute postradiation pneumonitis. The univariate analysis showed that the 

lung volumes receiving dose of 10 Gy, ipsilateral lung and total lung volume 

receiving 20 Gy, and total lung volume receiving dose of 30 Gy and 40 Gy increased 

the postradiation pneumonitis risk. The multivariate analysis showed 

that only the total lung volume receiving dose of 10 Gy was correlated with 

increased risk of postradiation pneumonitis (p=0,01). 

Conclusions: The acute postradiation pneumonitis is the relevant clinical 

problem in patients who underwent radical radiotherapy for NSCLC. The lung 

volume receiving dose of 10 Gy is the most important dosimetric factor which 

influenced the postradiation acute pneumonitis. 

914 poster 

TOWARDS A BETTER PREDICTION OF RADIATION-INDUCED 

LUNG DAMAGE (RILD) USING THERAPY AND PATIENT RELATED 

PARAMETERS 

A. Houben 1 , H. Aerts 1 , P. Lambin 1 , A. Dekker 1 , D. De Ruysscher 1 

1 MAASTRO CLINIC, Department of Radiation Oncology, Maastricht, 

Netherlands 

Purpose: Radiation therapy is frequently used to treat tumors in and around 

the thoracic region, such as lung and breast cancer. A commonly found complication 

is radiation-induced lung damage (RILD), which can result in significant 

morbidity. An accurate prediction of the risk at RILD before the initiation 

of therapy is therefore of great clinical importance. The dosimetric parameters 

used nowadays to predict RILD (e.g. MLD, V20, NTCP) in NSCLC patients 

have a low accuracy, typically with AUC’s of 0.60. We hypothesized that the 

prediction of RILD with the MLD could be improved by using a more accurate 

dose calculation algorithm in combination with functionality corrections of the 

lung tissue. These functionality corrections include sorting out the air filled 

cavities (bullae) from the total lung volume and converting the physical dose 

into a normalized total dose distribution. 

Materials: CT images and follow up data of 73 NSCLC lung cancer patients 

were used. A fast fourier transform (FFT) convolution and an multi grid (MG) 

superposition algorithm were compared using a dosimetric parameter (MLD). 

Functionality corrections were made by converting the dose distributions into 

a normalized total dose distribution (NTD), with corrections made for the fractionation 

as well as fractionation in combination with overall treatment time, 

and by sorting out bullae from the total lung volume. Other patient-related parameters, 

like the pre-treatment lung function parameters (FEV1 and DLco), 

were also related to RILD. Univariate logistic regression was used to correlate 

all parameters to the incidence of RILD. 

Results: The convolution algorithm overestimated the MLD with 5,4%, compared 

to the superposition algorithm. The predictive abilities of all MLD derived 

parameters were limited (AUC = 0,50 0,57), so using a different dose 

calculation algorithm as well as correcting for functionality of the lung tissue 

does not significant increase the predictive abilities of the MLD. RILD was significantly 

correlated with pre-treatment lung function parameters (FEV1 and 

DLco), which show good predictive power (AUC = 0,71 and AUC = 0,67 respectively).

S 292 CLINICAL/DISEASE SITES : OTHER TUMOR SITES 

Conclusions: So we can predict RILD best from a single pre treatment patient 

related parameter called FEV1, with a AUC of 0,71. Thus, patients with a 

restricted pre-treatment lung function, especially FEV1 and Dlco, appear to be 

more vulnerable for developing RILD after radiotherapy. An analysis of 73 patients 

showed that improvement of the MLD, using dose corrections, does not 

significantly better predict RILD than the uncorrected MLD. Future research, 

combining treatment as well as patient related parameters using machine 

learning techniques, could even further improve the predicting power. 

915 poster 

USE OF MAXIMUM INTENSITY PROJECTIONS (MIPS) FOR TARGET 

OUTLINING IN 4DCT PLANNING FOR NSCLC 

R. Muirhead 1 , C. Featherstone 1 , S. Muscat 2 , S. McNee 2 

1 

THE BEATSON, WEST OF SCOTLAND CANCER CENTRE, Clinical Oncology, 

Glasgow, United Kingdom 

2 

THE BEATSON, WEST OF SCOTLAND CANCER CENTRE, Physics, Glasgow, 


Purpose: Four-dimensional CT (4DCT) makes it possible to define patientspecific 

margins for intra-fraction motion for NSCLC, as opposed to standard 

"population-based" margins. There is no consensus as yet on the best voluming 

method for these scans. Underberg et. al. [1] showed that for Stage I 

tumours, Maximum Intensity Projection (MIP) images are equivalent to using 

composite gross tumor volumes (GTV’s) from all 10 phases of a 4DCT. Ezhil 

et al [2] found differences in target volumes for the two techniques for various 

stages of tumour. We investigated both outlining methods with a particular 

interest in the more advanced stages which are more common. 

Materials: 4DCT data was collected from 14 sequential patients with NSCLC 

lung cancer who had received radical radiotherapy at The Beatson West of 

Scotland Cancer Centre. Only 1 patient was Stage I, 7 were Stage IIB and 

6 Stage were IIIA. An experienced clinician manually contoured the GTV on 

all 10 phases of each 4DCT dataset and on the MIP of the 4DCT dataset. 

The production of an individualized internal target volume was based on (a) 

the combination of GTVs from the 10 phases to produce ITV_10PHASE (b) 

the MIP contour, ITV_MIP, which already includes intra-fraction movement in 

the scan. The outlines were compared to assess volumes of overlap and 

exclusion. 

Results: The Stage I patient had almost identical volumes and centre of mass 

using both methods. In Stage II and Stage III tumours, the ITV_10PHASE 

was significantly bigger than the ITV_MIP in all patients. There was a median 

of 19% (range 7% - 36%) of the volume of ITV_10PHASE not covered 

by the ITV_MIP. These were usually located in sites of equal or greater density, 

such as within the mediastinum or at the diaphragm. In contrast there 

was a median of 2.5% (range 0.5 - 10%) of the ITV_MIP not covered by the 

ITV_10PHASE. These small differences in volume were scattered around the 

edges of the ITV and were not considered to be of clinical significance. 

Conclusions: For the Stage I patient, our findings were in keeping with Underberg 

et.al. In Stage II and III tumours, we found in accordance with Ezhil 

et.al. All three studies would suggest that the MIP is not a completely reliable 

image set to use when contouring node positive NSCLC. MIPs give poorer 

resolution of nodal disease in the vicinity of higher density tissue than is found 

for the individual 10PHASE image sets. Determining an optimal method of 

outlining requires further investigation. Outlining all 10PHASE image sets 

is extremely time-consuming as only 2 image sets can be registered at any 

time. Stage I NSCLC tumours can possibly be outlined on the MIP alone. Efficient 

outlining for more advanced stages may require software development 

or derivation and application of suitable ITV to PTV margins. 

916 poster 

USING HYPERPOLARISED HELIUM-3 MRI TO DETECT CHANGES 

IN VENTILATION AFTER RADICAL LUNG RADIOTHERAPY 

O. Din 1 , J. Wild 2 , N. Woodhouse 2 , J. Swinscoe 1 , M. Hatton 3 , R. Ireland 

4 

1 

UNIVERSITY OF SHEFFIELD, Academic Unit of Clinical Oncology, Sheffield, 


2 

UNIVERSITY OF SHEFFIELD, Academic Unit of Radiology, Sheffield, United 

Kingdom 

3 

SHEFFIELD TEACHING HOSPITALS NHS FOUNDATION TRUST, Department 

of Clinical Oncology, Sheffield, United Kingdom 

4 

UNIVERSITY OF SHEFFIELD, Academic Units of Clinical Oncology and 

Radiology, Sheffield, United Kingdom 

Purpose: As with SPECT, hyperpolarized helium-3 MRI (3He MRI) may be a 

useful supplementary tool for the evaluation of lung cancer radiotherapy (RT) 

and its side effects. The aim of this study was to test the feasibility of using 

3He MRI to evaluate radiation induced lung changes. 

Materials: 4 NSCLC patients who received a radical dose of radiotherapy 

were assessed using this technique. All had both pre and post treatment CT 

and 3He MRI. 3He gas was polarized on site and ventilation images were 

acquired during a single breath-hold of a 1L 3He/N2 mixture. 3He MRI was 

performed on a 1.5T whole body system with the patient in the treatment po- 

sition. Ventilation images were acquired before radiotherapy (on the same 

day as planning CT) and three months following the end of treatment. Pre 

and post treatment MRIs were registered to each other and to the treatment 

planning and post treatment CTs, using anatomical landmark based rigid registration. 

Once registered, the 3He MR images were fused with the dose 

distribution calculated from the original treatment plan. 

Results: In all 4 patients, a reduction in ventilation was seen in the high dose 

volume. In 3 of these, this reduction correlated well with radiation induced 

damage apparent on CT. In 1 case, improved ventilation occurred as a result 

of tumour response. This patient had a 5cm left upper lobe adenocarcinoma 

with associated collapse (T4 N0). Pre RT images showed a large ventilation 

defect at the site of the primary tumour and collapsed lung. In addition, 

peripheral ventilation defects in both lungs were seen. Post RT, a response 

in the primary has been shown by resolution of the lobar collapse on CT. 

This is matched by an improvement in the 3He ventilation in the left upper 

lobe. In addition, CT has shown evidence of pneumonitis in the left lower 

lobe. The 3He images show a decrease in the functional area of ventilation 

in this region. Correspondingly, DLCO reduced by 16%. Review of the dose 

distribution suggests this area received approximately 38Gy. 

Conclusions: 3He MRI ventilation provides a novel and safe method of assessment 

of functional lung pathophysiology. This study has shown changes 

in 3He MRI ventilation can correlate well with both tumour response and radiation 

induced lung injury. Further work is required to assess its use in the 

earlier detection of pneumonitis and its potential as a predictive tool. 

Clinical/Disease sites : Other tumor 

sites 

917 poster 

3D - CONFORMAL EXTERNAL IRRADIATION WITH CONCURRENT 

WEEKLY GEMCITABINE AND CISPLATINUM AS PRESERVATION 

THERAPY FOR TRANSITIONAL CELL BLADDER CARCINOMA. A 

PHASE I DOSE ESCALATION TRIAL. 

H. Varveris 1 , E. Petinellis 1 , M. Mazonakis 2 , J. Stratakis 2 , F. Zacharopoulou 

2 , A. Fasoulaki 1 , E. Lyraraki 1 , S. Kachris 1 , A. Varveris 1 , A. Tzedakis 1 , 

M. Xenaki 1 , M. Kotronaki 1 , J. Damilakis 2 

1 UNIVERSITY HOSPITAL OF CRETE, Radiation Oncology, Heraklion, Greece 

2 UNIVERSITY HOSPITAL OF CRETE, Medical Physics, Heraklion, Greece 

Purpose: Although the use of radical transurethral resection (TUR) followed 

by concomitant chemoradiation leads to a similar overall survival when compared 

to cystectomy, the optimal treatment remains to be elucidated. A phase 

I study was conducted to evaluate the dose limiting toxicity (DLT) and the maximum 

tolerated dose (MTD) of Gemitabine (GEM) given concurrently with 3Dconformal 

radiotherapy (3D-CRT) and cisplatinum (CDDP) for patients with 

transitional cell locally advanced bladder cancer. 

Materials: Twenty four patients (19 male, 5 female), median age 72 years 

with clinical stage T2 (n=10), T3 (n = 8), and T4α (n = 6) without distant 

metastases, were enrolled, after macroscopically complete TUR. They all received 

3D CRT with a 18-MV Linear Accelerator, 70.2 Gy conventionally 

fractionated (1.8 Gy per day, 5 days a week , box technique) over 8 weeks. 

The GEM starting dose of 50 mg/m2/week was increased by 50 mg/m2 increments 

to 2 levels (100 and 150 mg/m2 /week) in cohorts of 6 patients. 

The standard dose of CDDP was 20 mg/m2 given 2 days after GEM infusion, 

once weekly. Both drugs were given 30 to 60 minutes before RT. 

Results: All patients were evaluated for toxicity. The DLT was defined as the 

occurrence of any of the following: 1) grade 3 neutropenia / thrombocytopenia 

2) non hematologic toxicity d grade 3, as abdominal pain / diarrhea (proctitis), 

dysuria / frequency (cystitis) not resolving to grade 1/2 within 2 days and 

grade 2/3 asthenia / fatique 3) any adverse event necessitating the interruption 

of RT for 1 week, arising in more than 3 of 6 patients in each cohort: 

The GEM dose immediately before the level at which the DLT was observed 

was defined as the MTD level. Six cases accrued to level 1 (GEM dose 50 

mg/m2/week). No grade 3 or 4 toxicities were seen. From 6 patients included 

at level 2, 2 had episodes of grade 3 bladder toxicity, while 3 presented with 

grade 3 hematological sequelae. From 6 patients accrued to level 3, 5 had 

episodes of grade 3/4 neutropenia and / or thrombocytopenia and 3 showed 

grade 3 asthenia / malaise. In 4 patients treatment was interrupted for more 

than 1 week. The remaning 6 patients were treated at the 100 mg/m2/week. 

GEM dose level. 

Conclusions: The MTD of GEM given concurrently with CDDP and RT was 

determined at the 100 mg/m2/week dose level, while DLTs were reached at 

the 150 mg/m2/week GEM dose level. The above chemoradiation schema 

is a tolerated regimen, easy to administer in ambulatory patients and merits 

further consideration in phase II trials.

918 poster 

CAN RADIATION THERAPY CONVERT TO COMPLETE REMISSION 

AGGRESSIVE NON-HODGKIN’S LYMPHOMA PATIENTS WITH 

LOCALISED PET-POSITIVE RESIDUAL DISEASE AFTER SYSTEMIC 

THERAPY? 

A. R. Filippi 1 , L. Todisco 1 , A. Chiappella 2 , A. Lucchini 3 , C. Marinone 4 , 

G. Parvis 5 , C. Tarella 6 , U. Vitolo 2 , U. Ricardi 1 

1 UNIVERSITA DI TORINO, Radiation Oncology, Torino, Italy 

2 A.S.O.U. S. GIOVANNI BATTISTA, Hematology, Torino, Italy 

3 OSP. AMEDEO DI SAVOIA, Infectious Diseases, Torino, Italy 

4 A.S.O.U. S. GIOVANNI BATTISTA, Torino, Italy 

5 A.S.O.U. S. LUIGI, Hematology, Orbassano, Italy 

6 UNIVERSITA DI TORINO, Hematology, Torino, Italy 

Purpose: To retrospectively investigate the impact of radiation therapy (RT) in 

patients affected by aggressive Non-Hodgkin’s Lymphoma (NHL) with limited 

PET-positive residual disease after first line or salvage chemo (CT) or chemoimmunotherapy 

(CT-IT). 

Materials: From May 2004 to June 2007, 16 patients were treated and selected 

for analysis: 10 had a diagnosis of Diffuse Large B-Cell, 1 of Follicular 

grade 3B, 3 of Burkitt’s and 2 of Diffuse Small Cell NHL. One patient presented 

as stage I, 6 as stage II, 2 as stage III and 8 as stage IV disease 

at diagnosis. Ten patients were treated with RT after first-line CT or CT-IT, 

including frontline high-dose CT (HDCT) and auto-grafting (ASCT) in 1 case 

with high-risk disease, and 6 after salvage treatments (3 after HDCT-ASCT). 

All patients had a positive PET finding after systemic therapy in sites of disease 

at diagnosis, and 11/16 (69%) repeated a PET scan 3 months after RT. 

In 5/16 patients (31%) response after RT was evaluated only on CT scans 

(in 2/5 because of clear disease progression after the end of RT). Globally, 

14/16 were in partial response after systemic therapy and 2 in stable disease. 

RT doses ranged from 25 to 36 Gy, on the basis of residual disease site and 

prior CT. Median follow-up time (from the start of RT to the last observation) 

was 12 months (range 1-43). 

Results: Response was evaluated with modified criteria for NHLs (2007). 

Thirteen patients were converted to complete remission after RT (10 PET 

negative and 3 in CR on CT scans); 12/13 are alive and disease-free without 

any other treatment and 1 is alive and disease-free after allogeneic transplantation. 

One had a partial response after RT on PET scans (reduction of 

50% of Standard Uptake Value) and is persistently positive without relapse in 

other sites and 2 had progressive disease (1 died shortly after RT, 1 after 7 

months). 

Conclusions: In patients sensitive to systemic therapy, with at least a partial 

response, RT seems to have a role in obtaining a high rate of complete 

remissions (92.8%, 13/14), with a potential impact on survival. In refractory 

chemo-resistant aggressive lymphomas, the role of RT appears to be only 

palliative. 

919 poster 

CONSOLIDATING RADIOTHERAPY AFTER CHEMOTHERAPY FOR 

HIGH-RISK NON-HODGKIN?S LYMPHOMA: STILL A MATTER OF 

INTEREST! 

D. Grootenboers 1 , M. van de Pol 2 , P. Poortmans 2 

1 UMCG, Radiotherapy, Groningen, Netherlands 

2 BVI, Radiotherapy, Tilburg, Netherlands 

Purpose: The primary treatment for stage >= II aggressive non-Hodgkin’s 

lymphoma (NHL) consists of 6 to 8 cycles of chemotherapy. The role of consolidating 

radiotherapy for high-risk patients is a matter of debate for many 

years. Against this background, we retrospectively analysed the outcome of 

all our patients consecutively treated with curative intent with consolidating 

radiotherapy after chemotherapy. 

Materials: From 1972 to 2005, we treated 181 patients for stage >= II NHL 

after chemotherapy. The vast majority of 160 patients was irradiated in the 

framework of the initial combined modality treatment. A total of 76 patients 

had a complete response and 84 had residual disease at the time of their 

referral for radiotherapy. As a separate group, 21 patients were irradiated after 

salvage chemotherapy for recurrent disease. All patient files were evaluated 

and updated if required. 

Results: The median age at the time of referral for radiotherapy was 61 years 

(range 9 - 83); 105 were male en 76 female. The median follow-up time for 

surviving patients is 4.7 years (0.3-33). Radiotherapy was given according to 

the "iceberg principle", or the "involved field", "extended field" and "involved 

nodal" concepts or to residual disease only in 49 (27%), 100 (55%), 4 (2%), 

18 (10%), 10 (6%) patients, respectively. The 5 year overall survival is 63% in 

the initially irradiated group with a CR after chemotherapy, 58% in the initially 

irradiated group with residual disease and 35% in patients irradiated for a 

recurrence (median survival 10.0 years, 9.0 years and 3.1 years respectively). 

Disease free survival at 5 years is 61%, 60% and 37% (median 10.0, 10.0 

and 2.1 years), respectively. In 28 out of the 73 patients who developed a 

recurrence of the disease after combined modality treatment, the disease 

recurrence was (at least partially) within the original radiation field. The acute 

radiotherapy related toxicity was grade 1 or less in 145 patients (80%), grade 

CLINICAL/DISEASE SITES : OTHER TUMOR SITES 

S 293 

2 in 34 (19%) and grade 3 in 2 patients. Late toxicity was not reported. 

Conclusions: The outcome of our patients in this non-selected group of highrisk 

NHL treated with consolidating radiotherapy after induction chemotherapy 

compares favourably with the results published in the literature. The presence 

of residual disease after chemotherapy or the radiotherapy technique had no 

influence on the outcome but patients who were treated for recurrent disease 

experienced a worse prognosis. Radiotherapy-related toxicity was very mild. 

Therefore, we advise to consider consolidating radiotherapy to high-risk NHL 

patients after induction chemotherapy. 

920 poster 

CURATIVE TREATMENT WITH RADIATION THERAPY FOR EXTRA- 

MAMMARY PAGET’S DISEASE 

M. Hata 1 , I. Ogino 1 , M. Omura 1 , I. Koike 1 , S. Kurihara 1 , Y. Tayama 1 , T. 

Inoue 1 

1 YOKOHAMA CITY UNIVERSITY GRADUATE SCHOOL OF MEDICINE, 

Radiology, Yokohama, Japan 

Purpose: Extramammary Paget’s disease (EMPD) is a relatively rare malignancy 

that usually arises in external genitalia. Wide surgical resection remains 

the standard and most reliable curative treatment for EMPD. However, 

as many EMPD patients are elderly and have coexistent diseases, surgical 

procedures are frequently inappropriate. There have been a few reports on 

treatment results from radiation therapy; thus we carried out a review to determine 

the role of radiation therapy in EMPD. 

Materials: Twenty-one patients, 4 men and 17 women, aged 52 to 94 years 

(median, 72) at irradiation, with EMPD in external genitalia underwent radiation 

therapy with curative intent. The clinical stage at diagnosis was T2-3N0- 

1M0; 7 patients had regional lymph node metastases but none had distant 

metastasis. A total dose of 45-70.2 Gy (median, 60 Gy) in 25-39 fractions 

(median, 33 fractions) was delivered to the pelvis including tumors. 

Results: In all patients but two, the irradiated tumors were controlled during 

the follow-up period of 8-114 months (median, 38) after treatment. Nine patients 

had recurrences including local recurrences within the radiation fields 

in 2 and lymph node or/and distant metastases outside the radiation fields in 

7 at 3-43 months after treatment. The local control rates were 90% at both 

2 and 5 years. Five patients died 33-73 months after irradiation; the causes 

of death were tumor progression in 2, infectious pneumonia in 2, and renal 

failure in 1. The overall and cause-specific survival rates were 100% each 

at 2 years, and 53% and 93%, respectively, at 5 years. No therapy-related 

toxicity of grade 3 or greater was observed. 

Conclusions: Radiation therapy was effective and safe for patients with 

EMPD and appeared to contribute to prolonged survival as a result of good 

tumor control. 

921 poster 

DISTRIBUTION OF PLEURAL DISSEMINATION FROM THYMIC 

TUMORS: IMPLICATIONS FOR PROPHYLACTIC IRRADIATION TO 

THE PLEURA 

S. Otsuka 1 , Y. Shibamoto 1 , M. Hara 1 , S. Sasaki 1 , C. Sugie 1 , C. 

Ikeya-Hashizume 2 , H. Ogino 1 , F. Baba 1 , H. Iwata 1 , T. Kawai 1 , M. Mimura 

3 

1 NAGOYA CITY UNIVERSITY, Radiology, Nagoya, Japan 

2 NAGOYA KYOURITSU HOSPITAL, Radiology, Nagoya, Japan 

3 NAGOYA DAINI RED CROSS HOSPITAL, Radiology, Nagoya, Japan 

Purpose: Thymoma and thymic cancers often develop pleural dissemination. 

To treat or prevent pleural dissemination, radiation therapy appears to play an 

important role. Entire hemithorax irradiation using a conventional technique 

has been advocated by some groups, but with this method, only a limited 

total dose can be delivered to the whole pleura due to adverse effects against 

normal lung. With intensity-modulated radiation therapy (IMRT), the whole 

pleura can be covered while reducing the dose to the lung. However, when 

all the interlobar pleuras are included in the target volume, radiation doses 

to the lung become higher, even by using IMRT, and consequently the dose 

to the pleura cannot be increased sufficiently. In this study, we investigated 

distribution of pleural disseminations from thymic tumors, and evaluated the 

possibility for omitting the interlobar pleuras from the IMRT field. 

Materials: CT images of the entire thorax in 30 patients with pleural disseminations 

from thymic tumors were evaluated. These patients had pleural 

disseminations either at initial presentation or recurrence. Patients with more 

than 20 lesions were excluded. The whole pleura was divided into the following 

6 parts: upper and lower (divided at the carina level) mediastinal, upper 

and lower costal, diaphragmatic, and interlobar parts. Using a tomotherapy 

work station, IMRT plans for the whole-pleural irradiation to deliver 20 Gy with 

or without irradiation to the interlobar part were created and compared. 

Results: There were 117 disseminated lesions. Pleural disseminations were 

seen in the lower costal part in 52 lesions (20 patients), the diaphragmatic 

part in 32 (15 patients), the lower mediastinal part in 14 (10 patients), the 

interlobar part in 11 (8 patients), the upper costal part in 6 (6 patients), and 

the upper mediastinal part in 2 (in 2 patients). No patients had lesions in


bilateral thoraxes. Dissemination on the interlobar pleura was seen in 27% 

of the patients and in 9% of all 117 lesions. Pleural disseminations tended 

to develop much more often in the lower thorax. There were no correlations 

between the percentage of patients with interlobar lesions and age, sex, laterality 

of the thorax, and WHO histological classification. When the whole 

pleuras were included in the IMRT field, the V5Gy, V10Gy and V15Gy for the 

lung were 57%, 41%, and 34%, respectively, while they were 53%, 34%, and 

25%, respectively, in a plan excluding the interlobar pleura. 

Conclusions: Pleural disseminations were detected in all parts of the pleura, 

including the interlobar part. All lesions existed only within the hemithorax. 

For prophylactic pleural irradiation, the interlobar pleura cannot be excluded 

from the clinical target volume. Even so, higher doses appeared deliverable to 

the whole pleura by using tomotherapy as compared to conventional hemithorax 

irradiation. 

922 poster 

EFFICACY OF RADIOTHERAPY IN CLASSICAL KAPOSI’S 

SARCOMA EITHER WITH SINGLE DOSE OR FRACTIONATED 

RADIOTHERAPY 

S. Akyurek 1 , F. Yildiz 2 , Y. Pak 3 , S. Surenkok 4 , A. F. Korcum 5 , S. Kamer 

6 , F. Tokatli 7 , B. Baltalarli 8 , A. Haydaroglu 6 

1 

ANKARA UNIVERSITY SCHOOL OF MEDICINE, Radiation Oncology, Ankara, 

Turkey 

2 



3 

GAZI UNIVERSITY SCHOOL OF MEDICINE, Radiation Oncology, Ankara, 

Turkey 

4 

GULHANE UNIVERSITY SCHOOL OF MEDICINE, Radiation Oncology, 


5 

AKDENIZ UNIVERSITY SCHOOL OF MEDICINE, Radiation Oncology, 

Antalya, Turkey 

6 

EGE UNIVERSITY SCHOOL OF MEDICINE, Radiation Oncology, Izmir, 

Turkey 

7 

TRAKYA UNIVERSITY SCHOOL OF MEDICINE, Radiation Oncology, Edirne, 

Turkey 

8 

PAMUKKALE UNIVERSITY SCHOOL OF MEDICINE, Radiation Oncology, 

Denizli, Turkey 

Purpose: To retrospectively evaluate the efficacy of single fraction or fractionated 

radiotherapy in patients with classical Kaposi’s sarcoma (CKS) 

Materials: In this retrospective analysis 128 patients with CKS who were 

treated between January 1991 and September 2007 in 8 centers in Turkey 

were included. Median age was 65 (range 18-87). The male to female ratio 

was 2.8. Disease was confined to extremities in 95% of cases, and lower 

limbs were the most frequent sites of the involvement. Only in the 5% of 

cases, lesions were localized in the trunk. Five patients (4%) had visceral 

involvement at the time of diagnosis and 13 patients (10%) had an underlying 

immunocompromised state. Of the 325 fields treated, 90 were with fractionated 

regimen as 10-40 Gy in 2-20 fractions. The other 235 fields were iradiated 

with 5-10 Gy of single doses. The majority of lesions (92%) were treated 

with 3-10 MeV electron beams while 6% of lesions were treated with Co60 

teletherapy unit , remaining 2% of patiens were treated with 195-200KVp Xray. 

Results: Median follow-up time was 48 months (1-130 months) for the whole 

populations. At the last follow-up complete and partial response rates were 

%75 and %17, respectively. Twenty patients (8%) had stable or progressive 

disease. The overall response rates achieved with fractionated and single 

high dose radiotherapy were 100% and 87%, respectively (p=0.04). Complete 

and partial response rates for fractionated and single high dose radiotherapy 

were 79%, 21% and 72%, 15%, respectively. In both dose group 

various degrees of hyperpigmentation, mild edema and fibrsis were detected. 

The difference was not statistically significant. 

Conclusions: Our long term results suggest that fractionated radiotherapy 

is highly effective in controlling the CKS. If we consider in clinical practice it 

seems that single high dose radiotherapy is also effective and alternative of 

fractionated radiotherapy. 

923 poster 

EVOLUTION OF LUNG FUNCTION PARAMETERS IN RELATION TO 

THE MEAN LUNG DOSE DELIVERED DURING RADIOTHERAPY 

IN A TRI-MODALITY TREATMENT PROTOCOL FOR MALIGNANT 

PLEURAL MESOTHELIOMA (MPM). 

Y. Lievens 1 , B. Vanstraelen 1 , P. Nafteux 2 , K. Nackaerts 3 

1 UZ LEUVEN, Radiation Oncology, Leuven, Belgium 

2 UZ LEUVEN, Department of Thoracic Surgery, Leuven, Belgium 

3 UZ LEUVEN, Department of Pulmonology, Leuven, Belgium 

Purpose: To analyse the evolution in lung function parameters of MPM patients 

after hemi-thoracic radiotherapy with 3D conformal radiotherapy (3D- 

CRT) or intensity modulated radiotherapy (IMRT) as a function of the mean 

lung dose (MLD). 

Materials: Out of 43 patients included in a tri-modality protocol between 3- 

2003 and 12-2007, 22 patients have been referred for hemi-thoracic radiotherapy 

(RT) after 3 cycles of cisplatin-based induction chemotherapy and 

extrapleural pneumonectomy. Twenty patients completed the entire RT treatment 

(54Gy/1.8Gy), 4 of them received an additional boost of 10Gy/2Gy to 

areas of incomplete resection. All patients were evaluated for lung function 

changes (FEV1 - forced expiratory volume at 1 second and DLCO - diffusion 

capacity). 

Results: Of the 20 patients completing radiotherapy, 3 have not yet reached 

6 months follow-up. Two patients died within 6 months after RT: one due 

to metastatic disease, one because of overwhelming BOOP after RT (with a 

Vlung20 of only 5%, but a MLD of 16.5Gy). Three additional patients were 

excluded because of lacking lung function parameters at 6 months due to 

follow-up elsewhere. The remaining 12 patients were included in this analysis: 

3 were treated with 3D-CRT (all with left-sided mesothelioma and irradiated 

before 9-2006), 9 with IMRT (all except one were right-sided). The 

average MLD in the 3D-CRT plans was 3,3Gy (1,6Gy - 4,3Gy) and 9,8Gy 

(6,3Gy 13,1Gy) in case of IMRT. Patients were further divided into a high 

MLD (>9,5Gy) group comprising 5 patients and a low MLD (≤ 9.5Gy) group 

(7 patients), regardless of the treatment technique. The table shows the percentile 

change in lung function parameters (mean and range) between predicted 

post-operative values and the observed values at six months and 1 

year post-radiotherapy respectively. 

Conclusions: The better target coverage and organ sparing (especially of 

liver and heart) that generally results from the use of IMRT in treatment planning 

of MPM, should be pondered against a higher dose delivered to the 

remaining lung. In this series, a MLD greater than 9.5Gy did not translate 

into a worse pulmonary outcome within the first year after radiotherapy. Although 

the data are still limited, there seems to be a decline of lung function 

parameters over time, for which close follow-up is warranted. 

924 poster 

INTENSITY-MODULATED RADIOTHERAPY FOR THE TREATMENT 

OF MEDIASTINAL TUMOR MASSES IN PATIENTS WITH EARLY 

STAGE HODGKIN LYMPHOMA 

T. Girinsky 1 , M. Ghalibafian 2 , I. Ferreira 3 , N. Dessard 1 , A. Paumier 1 , T. 

Messai 1 

1 

GUSTAVE ROUSSY, Radiation Oncology, Villejuif, France 

2 

MAHAK HOSPITAL, Radiation Oncology, Aqdasieh, Tehran, Iran Islamic 

Republic of 

3 

GUSTAVE ROUSSY, Physics, Villejuif, France 

Purpose: To lessen the occurrence rate of late heart complications in patients 

with mediastinal Hodgkin lymphoma. 

Materials: Patients with early stage Hodgkin lymphoma or recurrent mediastinal 

disease were entered in the study. All patients were treated with 

chemotherapy prior to irradiation. The clinical target volume (CTV) was determined 

on the postchemotherapy CT simulation according to the recently 

published EORTC guidelines [1]. A 10-mm isotropic margin was added for 

the planning target volume (PTV). Dose constraints were systematically assigned 

to a virtual volume located behind the PTV and/or the coronary artery 

origins. The IMRT planning was performed with Helios Cadplan (Varian). Radiation 

doses varied from 30 Gy to 40 Gy. 

Results: Thirty patients with primary Hodgkin lymphoma and one patient 

with recurrent disease entered the study from January 2003 to April 2007. 

The median age was 29 years (range 17-75). Sixteen percent of the patients 

had a stage I and 84% were stage II. The chemotherapy treatment consisted 

of 3 to 6 cycles of ABVD. Twenty patients were given 40 Gy and in eleven 

patients radiation doses ranged from 21.6 Gy to 36 Gy. The median followup 

was 29 months (range 2-57). The 3-year progression-free survival and 

overall survival were 91.7% and 100% respectively. There was one in field 

recurrence in a patient with bulky mediastinal disease which was PET avid 

after 6 cycles of ABVD. Concerning radiation doses delivered to organs at 

risk, data could be retrieved for only 20 patients. The mean radiation dose 

delivered to the origin of the coronary arteries was 26 Gy and the mean heart 

V30 was 18.5%. 

Conclusions: Our preliminary results suggest that patients with mediastinal 

tumor masses can be treated with IMRT in order to protect organs at risk such 

the heart and the origin of the coronary arteries. [1] T. Girinsky, R. van der 

Maazen and L. Specht et al., Involved-node radiotherapy (INRT) in patients 

with early Hodgkin lymphoma: concepts and guidelines, Radiother Oncol 79 

(2006), pp. 270277.

925 poster 

LATE GASTRIC TOXICITY AFTER WHOLE STOMACH RA- 

DIOTHERAPY IN THE GASTRIC MALIGNANT LYMPHOMA : 

MULTI-INSTITUTIONS STUDY IN JAPAN 

H. Suefuji 1 , C. Hattoori 1 , C. Tsuji 1 , H. Eto 1 , G. Suzuki 1 , J. Uozumi 1 , E. 

Ogo 1 , N. Hayabuchi 1 

1 KURUME UNIVERSITY, SCHOOL OF MEDICINE, Radiation Oncology, 

Kurume, Japan 

Purpose: Recently, radiotherapy has become the standard therapies for the 

gastric malignant lymphoma in Japan. However, in out knowledge, there are 

no articles concerning the safety of the radiotherapy for the gastric malignant 

lymphoma. We dispatched a questionnaire to the institutions having Linier 

accelerator and investigated the safety of the whole stomach radiotherapy 

(WSRT). 

Materials: The gastric malignant lymphoma cases treated with WSRT in the 

period from January 1995 to March 2005 were investigated in this study. We 

selected the number of WSRT cases and investigated late gastric toxicity 

cases in each institutions. We intended for gastric toxicity after a half year after 

radiotherapy, because of the limitation of the late side effect in this study. 

We asked 121 institutions for investigation and got an answer from 57 institutions. 

Results: The numbers of WSRT were 637 in this period. DLBCL (diffuse 

large B-cell lymphoma), MALT lymphoma and the other histology and unknown 

cases, were 274 (42%), 268 (43%) and 95 (15%), respectively. The 

numbers of WSRT in each institutions over 30 cases, 20-29 cases, 10-19 

cases, 1-9 cases and zero case were 4, 7, 11, 29 and 6 institutions, respectively. 

There were only 5 of 637 cases (0.78%) about the late toxicity of the 

stomach. Three GVE (gastric vascular ectasia)-like mucositis cases (in the 

figure), one gastric perforation case and one secondary early gastric cancer 

case were shown in this study. There were no cases required total gastrectomy 

except one secondary gastric cancer case and no cases with relapsed 

malignant lymphoma in these 5 late toxicity cases. 

Conclusions: In conclusion, we thought about that WSRT for gastric malignant 

lymphoma could be very safety therapeutic method. It was difficult to 

confirm the cause of the late gastric toxicity after WSRT in this study. 

926 poster 

OUTCOMES OF RADIOTHERAPY FOR LOCALLY-ADVANCED 

BLADDER CANCER 

M. Murcia - Mejia 1 , V. Macías Hernández 1 

1 CAPIO-HOSPITAL GENERAL DE CATALUNYA, Radiation Oncology, Sant 

Cugat del Vallés (Barcelona), Spain 

Purpose: To investigate the pattern of failure after conservative treatment, as 

well as its early and late side effects. 

Materials: 29 consecutive inoperable G3 bladder cancer patients (T2-4 N0 

M0) were irradiated between 2-2003 and 122007. Concomitant chemotherapy 

(weekly cisplatin) was administered in 69% of patients plus neoadjuvant 

chemotherapy (cisplatin-gemcitabine) in 55%. Hydronefrosis was associated 

in 27.6% patients. Prescribed dose to PTV1 (empty bladder + 15-25 mm) 

was 50-62 Gy. Pelvic lymph node areas were included in 10 patients to a 

dose of 45-50.4 Gy. Total dose to PTV2 (macroscopic tumour + 10-15 mm) 

was 68.2±3 Gy (median 70 Gy). 3DCRT was performed in 20 patients with 

box technique and was 2.5D in 9 patients. Minimum PTV dose was 95% of 

CLINICAL/DISEASE SITES : OTHER TUMOR SITES 

S 295 

prescribed dose. RTOG was assessed prospectively according RTOG scale. 

Follow-up included cistoscopy with TUR and multiple random biopsies, citoloy 

and body CT. 

Results: Age 76.9±8.8. Mean follow-up is 26.5±16.8 months. Local recurrence 

was assessed in 8 patients, 5 in situ (17.2%) and 3 infiltrative (10.3%) 

at 12.4±9.1 months and 14.7±5.1 months respectively. The 3 patients with 

infiltrative local recurrence received a total PTV2 dose


928 poster 

RADIATION AS MONOTHERAPY IN OCULAR ADNEXAL MUCOSA- 

ASSOCIATED LYMPHOID TISSUE LYMPHOMA PATIENTS. SINGLE 

CENTER EXPERIENCE. 

A. Bilalis 1 , D. Demenagas 2 , P. Stefanitsi 1 , A. Sioni 1 , A. Pouli 1 , S. 

Tsakanikas 1 , K. Papanastasiou 1 , M. Nachat 2 , A. Sotiropoulou 2 , M. 

Stamatelou 1 

1 

ST. SAVVAS ANTICANCER INSTITUTE - HOSPITAL, Department of 

Haematology, Athens, Greece 

2 

ST. SAVVAS ANTICANCER INSTITUTE - HOSPITAL, Radiation Oncology, 


Purpose: Ocular adnexal mucosa-associated lymphoid tissue lymphoma 

(OAMALT) constitutes a specific entity of non Hodgkin lymphomas. It is 

mainly a slow growing tumor of B-cell, without a standard treatment management. 

Aim of our study is to present the clinical behaviour and the treatment 

outcome in OAMALT patients who received radiation therapy (RT). 

Materials: we retrospectively analyzed the medical records of 16 patients 

with OAMALT since 1999, who received RT monotherapy. Last follow up 

(FU) was January 2008. In all the patients the initial evaluation consisted 

of regional biopsy (histology and immunocytochemistry) , CT scan (visceral 

scull, thorax, abdomen), gastroscopy (biopsies and detection for H. pylori), 

and trephine bone marrow biopsy. Radiation therapy was performed with 

linear accelerators 6 MV after 3D conformal treatment planning. For patient 

immobilization thermoblastic mask was used. 

Results: sixteen patients (9 females and 7 males) stage IA, median age upon 

diagnosis 58 years (range 39 78) were evaluated. The initial management 

for all patients was RT (35-39Gy, 2Gy / fraction). Median FU was 49 months 

(6-102). During that time all the patients achieved complete remission (CR) 

except one patient who relapsed in the contralateral eye. Nine patients developed 

cataract in the treated eye. 

Conclusions: although the sample is limited, it seems that RT can be the 

treatment of choise in OAMALT patients stage IA. 

929 poster 

RADIOSENSITIVE METASTASES FROM RENAL CELL CARCINOMA 

USING BRACHYTHERAPY BOOST 

A. Richard Holm 1 , C. Mercke 2 , P. Wersäll 1 , E. Bengtsson 2 , U. Harmenberg 

1 , K. M. Kälkner 1 



Purpose: Describing a case of a 67 years old female suffering from metastases 

to the lower lip from a renal cell carcinoma (RCC) treated with combined 

external radiotherapy and high dose rate brachytherapy. Suggesting a good 

clinical response after delivering high doses of radiotherapy with a normalized 

total dose exceeding 90 Gy (2 Gy fraction equivalents and alpha/beta 

ratio equal to 3). 

Materials: In 2002 a female born 1942, previously healthy, non-smoker was 

diagnosed with a left sided RCC Fuhrman grade 3, stage T3a according to 

the TNM classification. The tumour was radically excised. In January 2004 a 

cerebral metastasis was treated with stereotactic radiotherapy. In March 2004 

lung metastases were treated with interferon (Introna R○3x106 IE three times 

a week) with partial regression of the lung metastases. However, the patient 

experienced severe fatigue during treatment and the interferon treatment was 

periodically paused. In August 2006 two soft tissue metastases developed in 

the lower lip. Rapid progression of these lesions occurred, and radiotherapy 

was initiated. From the 18th to 31st of August, a total dose of 30 Gy (3 Gy 

per fraction) was delivered using two opposed fields of photons (6 MV). The 

patient was hospitalised due to mucositis and subsequent nutritional deficiencies. 

From the 13th to 19th of September the patients received 30 Gy given in 

ten fractions (two fractions per day) using Ir-192 HDR implants. The dose plan 

was made using CT-images imported into the PLATO-brachytherapy planning 

system (Nucletron, the Netherlands) see figure. 

Results: One month later the tumours in the lower lip started to become 

necrotic and two months after radiotherapy the metastases have reduced 

more than 50%. In January 2007 the lip metastases were no longer palpable. 

However, on a CT of the brain several small metastases had developed 

and over a short space of time the patient deteriorated and was admitted to a 

hospice. The patient died in March 2007. 

Conclusions: Renal cell carcinoma is considered to be a radioresistant tumour, 

however, the use of high doses delivered with large fractions has overcome 

the resistance. Here we describe a method combining external and 

brachytherapy radiotherapy in a palliative setting to avoid mutating surgery. 

930 poster 

RADIOTHERAPY AND IMIQUIMOD IN MERKEL’S CELL CARCINOMA 

(MCC): A CASE REPORT 

E. Mazzeo 1 , M. Balducci 1 , B. De Bari 1 , S. Manfrida 1 , G. R. D’Agostino 1 , 

N. Dinapoli 1 , V. Valentini 1 

1 CATHOLIC UNIVERSITY OF SACRED HEART, Radiotherapy, Rome, Italy 

Purpose: Merkel’s Cell Carcinoma (MCC) is a rare primary small neuroendocrine 

cell skin tumour that occurs in the elderly. Literature strongly support 

postoperative radiotherapy to improve local control. We present a case of 

an old man presenting a Merkel’s carcinoma treated with the association of 

radiotherapy with imiquimod (Aldara. 

Materials: We present the case of a diabetic 82 years old man, treated with 

dialysis for a chronic renal insufficiency, presenting a MCC of the right zigomatic 

area. Despite surgery, a post-operative echography showed a residual 

disease. When we visited him the lesion was about 11 x 10 centimetres in diameter 

and appears as a firm, painless lump prominent on the skin for about 

1,5 cm, fixed on deep tissues. Parotid and zigomatic area with omolateral 

laterocervical limphnodes were treated by two angled, wedged fields, using 

a 6MV LINAC. Total dose on PTV has been 50,4 Gy (1,8 Gy/die). Concurrent 

imiquimod once a day on the zigomatic area interested by macroscopic 

infiltration and on the surrounding erythema was applied. 

Results: After 12 applications, the patient showed an acute G3 skin toxicity 

(RTOG), with a crust on the treated area that cleared up with a 3 week interruption 

of the integrated treatment. After the interruption, when the crust 

was removed, the underlying skin appeared completely re-epithelized, So, 

we decided to suspend concurrent imiquimod, continuing treatment only with 

radiation therapy. During this second part of the treatment, he experienced a 

G2 dermatitis and a G2 stomatitis. A clinical evaluation, performed 7 months 

after the end of radiotherapy, showed a complete response. A CT scan and 

a clinical evaluation of the treated area, performed 7 months after the radiation 

therapy, did not show any sign of local recurrence, with a very good local 

tropisms. 

Conclusions: This case report suggests a possible and effective use of immunomodulators, 

as imiquimod, as part of radiation therapies for cutaneous 

malignancies as MCC. Skin tolerance should be an important issue to consider. 

931 poster 

THYMOMA: LONG-TERM RESULTS OF TREATMENT AND ROLE OF 

RADIOTHERAPY 

M. Hetnal 1 , K. Malecki 1 , M. Wolanin 1 , S. Korzeniowski 1 

1 CENTRE OF ONCOLOGY, Breast and Thoracic Cancer Unit, Krakow, Poland 

Purpose: The aim of this study is to assess results of treatment, factors 

influencing prognosis with regard to causes of failure and treatment tolerance 

in patients with thymoma. 

Materials: Between 1966 and 2006, 63 patients with thymoma had been 

treated at the Centre of Oncology in Krakow. Median age was 43 years, 31 

patients were males, 32 were females. Main endpoints of the analysis were 

locoregional recurrence-free survival (LRRFS), disease free survival (DFS)

and overall survival (OS). Kaplan-Meier method was used to calculate survival 

rates. Univariate and multivariate analyses of prognostic factors were 

performed using log rank test and Cox’s proportional hazard method. Patients 

were treated by means of different treatment modalities: surgery followed 

by radiotherapy (52%), radiotherapy alone (13%), chemoradiotherapy alone 

(15%), surgery followed by chemoradiotherapy (5%), surgery alone (5%) and 

others. 

Results: The 10-year LRRFS was 79 %, DFS was 57% and OS was 

57%. Masaoka stage was the only independent prognostic factor for LRRFS. 

Masaoka stage and method of radiotherapy delivery (higher photon energies), 

were independent prognostic factors for OS. For DFS, the independent 

prognostic factors were age, type of treatment (favoured surgery followed by 

radiotherapy or chemoradiotherapy), Masaoka stage and year of start of treatment. 

Most common reactions were lung fibrosis in 36% of patients (mainly 

asymptomatic in most patients), pneumonitis (9%) and oesophagitis (4%). 

Conclusions: Surgery combined with radiotherapy and chemoradiotherapy 

and modern radiotherapy techniques are correlated with improvement of survival 

in patients with early stage thymoma. Anyway, in patients with very early 

stage thymoma the complete surgical excision seems to be sufficient method 

of treatment. 

932 poster 

TOTAL SKIN ELECTRON IRRADIATION (TSEI) FOR MYCOSIS 

FUNGOIDES ? CLINICAL RESULTS. RETREATMENT POSSIBLE? 

M. Doleckova 1 , P. Berkovsky 1 , A. Studynkova 1 

1 NEMOCNICE CESKE BUDEJOVICE A.S., ONO, Ceske Budejovice, Czech 

Republic 

Purpose: TSEI therapy is a complex method for delivering superficial irradiation 

to entire skin surface for patients with cutaneous T-cell lymphoma especially 

with mycosis fungoides (MF). The majority of patiens has recurrence 

after TSEI eventually. Some patients may be candidates for a second course 

of TSEI. The purpose of this report is to evaluate short and long-term clinical 

results of TSEI and using this metod for retreatment. 

Materials: Thirty six patients (p.) with MF received TSEI in Department of 

Oncology, Reg. Hospital C. Budejovice, Czech Republik (1993- 2007). There 

were 26 male, 10 female, the average age 62. Diferent treatments modalities 

have been used prior to TSEI for 24 patients. TSEI technique developed at 

McGill University, Montreal (Freeman C.R., 1992) was modified to our conditions. 

The patient standing in position ballet dancer" rotates on a carrousel. 

Two oblique fields produce a uniform treatment field" over the total length patient 

for SSD 355 cm, 6 MeV electrons. By rotational radiotherapy technique 

(n=26) maximal dose is achieved on the surface of the skin. By stationary radiotherapy 

technique (n=10) is on the surface 88% (max. dose in 9 mm) with 

plexi, without plexi 77% (max. dose in 14 mm). A total dose was 30-40 Gy 

(10 Gy / week). Dose distribution was monitored with set of TLD dosimetres 

with subsequent patch" (n=36) and boost" treatments (n=22). Some patiens 

with relaps were candidates for second course of TSEI after other failed treatment. 

Seven patiens had TSEI retreatment with average dose 23 Gy (6-30 

Gy), average total dose (inicial plus repeated TSEI) was 64 Gy (46-88 Gy). A 

second complete course of intense TSEI was administered to 2 p. Average 

time for repeating TSEI was 35 months. Third course TSEI was offered to 2 

patients, total dose 70 Gy and 88 Gy. 

Results: Response to initial TSEI was in 100% (n=36). Complete response 

has been seen in 95% (34/36), 15 p. (42%) are alive (10 p. without MF, 5 p. 

with MF), 21 p. (58%) died (10 p. died from progressive MF, 11 p. from other 

cause). Overall survival (n=36) (by Kaplan-Meier): 3-survival rate was 68- 

72%, 5-survival rate was 52%, 10-survival rate was 11%. Results achieved 

are not statistically significant, the group of patients is too small. Relaps: 

61% p. (21/36). Good paliation effect has been achieved for all patients with 

repeating TSEI, relief of symptoms, for someones only for short time, average 

was 10,5 months (1-29). 

Conclusions: Most patiens with MF have benefit from TSEI. Some patients 

achieved long-standing remission, patients with advance disease effective 

palliation. The repeating TSEI offers next posibility for paliative treatment. 

TSEI retreatment improves quality of life for all patients. 

Clinical/Disease sites : Others 

933 poster 

BEXXAR PROTOCOL CP98-020 : RESULTS WITH I-131 LABELED 

ANTIBODY IN PATIENTS WITH NON-HODKIN’S LYMPHOMA RE- 

FRACTORY TO CHEMOTHERAPY AND RITUXAN : A REPORT OF 50 

CLINICAL/DISEASE SITES : OTHERS 

S 297 

CASES 

D. Quick 1 , R. Mark 2 , P. Anderson 2 , T. Neumann 2 , M. Nair 2 , R. Akins 3 

1 

JOE ARRINGTON CANCER CENTER, Department of Medical Oncology, 

Lubbock, USA 

2 

JOE ARRINGTON CANCER CENTER, Department of Radiation Oncology, 

Lubbock, USA 

3 

UNIVERSITY OF MIAMI, Department of Radiation Oncology, Miami, USA 

Purpose: Non-Hodgkin’s Lymphoma (NHL) B-Cell subtype, is generally very 

sensitive to Chemotherapy and Rituxan. In patients who have developed refractory 

disease, the course of disease is usually rapidly fatal. Many NHL 

B-Cells express CD-20 Antigen. Such patients may be candidates for Radioimmunotherapy 

(RIT) with tositumomab murine monoclonal antibody conjugated 

with I-131, which can bind to CD-20 expressing cells with potentially 

lethal effects. We present results in 50 patients treated according to the 

Bexxar CP98-020 Protocol. 

Materials: Initially, candidates for Bexxar CP98-020 Protocol, were patients 

with NHL expressing CD-20 which had become refractory to Chemotherapy 

and Rituxan. Since 2006, four patients have received primary treatment for 

NHL with RIT. Eligibility criteria included Platelet count > 100,000, less than 

25% involved bone marrow, and no kidney dysfunction. In addition, the patients 

could not be pregnant or breast feeding. Between 2001 and 2008, 50 

patients received I-131 labeled Antibody. The total body dose was 75 cGy for 

Platelet counts > 150,000 and 65 cGy for Plt 100-150,000. Activity ranged 

from 60 mCi to 120 mCi. 

Results: Median follow-up was 48 months (range 6-84 months). The response 

rate was 72.0% (36/50), with complete response achieved in 28.0% 

(14/50) of the patients. Median progression free survival was 14 months. All 

four patients treated with primary RIT remain free of recurrence, with followup 

periods ranging from 8-36 months. Toxicity was moderate, with 10.0 % 

(5/50) of patients experiencing profound (Platelets < 10,000) thrombocytopenia, 

which was prolonged, lasting more than 20 weeks. There were no bleeding 

complications, and no patient required a transfusion. For the remaining 

45 patients, Plt counts decreased mildly for 4-6 weeks following RIT, and then 

returned to normal values by 10-20 weeks. 

Conclusions: RIT has yielded promising results in NHL patients refractory 

to Chemotherapy and Rituxan. Toxicity has been acceptable. While follow-up 

is short, RIT may be considered for first line treatment in some cases of NHL. 

934 poster 

DETERMINATION OF THE DOSE-RESPONSE RELATIONS OF 

ACOUSTIC NEUROMAS AFTER TREATMENT WITH GAMMA KNIFE 

E. Koutsouveli 1 , P. Mavroidis 2 , P. Karaiskos 3 , P. Sandilos 4 , C. Stergiou 1 , 

M. Torrens 1 

1 

HYGEIA HOSPITAL, Department of Radiosurgery and Medical Physics, 


2 

KAROLINSKA INST. AND STOCKHOLM UNIVERSITY, Department of Medical 


3 

UNIVERSITY OF ATHENS, Department of Medical Physics, Medical School, 


4 

ARETEION UNIVERSITY HOSPITAL, Department of Radiology, Athens, 

Greece 

Purpose: The purpose of this work is to examine factors that are related with 

the response of acoustic neuromas after Gamma Knife radiosurgery. This 

is accomplished by associating dosimetric measures and other treatment related 

parameters with the clinical follow-up results. 

Materials: This study examines 25 patients who were treated for acoustic 

neuromas with the Leksell Gamma Knife (model C) unit, which is equipped 

with an automated positioning system (APS). The treatment outcome and 

the dose distribution delivered to the target were available for each patient. 

The dedicated GammaPlan treatment planning system was used for the development 

of the treatment plans based on CT and MRI images using the 

stereotactic frame in position. Clinical and radiological findings were used for 

assessing target response, which is express as a significant size reduction of 

the target volume (response group). All the patients had at least 2 years of 

follow-up. 

Results: The mean age of the patients in the response group is 60.3 y, 

whereas in the non-response group it is 54.2 y. The corresponding prescribed 

doses range between 11-12 Gy with a mean reference isodose of 

49% (45-54%) and 11-14 Gy with isodose 47% (40-50%), respectively. The 

initial target volume in the response group is 5.5 cc (0.7-12.1 cc), whereas 

in the non-response group it is 5.0 cc (0.2-19.3 cc). For the two groups of 

patients the mean and minimum doses (Dmean, Dmin) are 15.8 and 8.5 Gy 

and 16.4 and 8.1 Gy, respectively. The average volume receiving 10 and 12 

Gy is 6.3 and 4.4 cc for the response group and 6.5 and 3.8 cc for the nonresponse 

group, respectively. Finally, the average conformity index was 0.8 

(0.5-0.9) in the response group and 0.8 (0.7-0.9) in the non-response group, 

respectively. A positive association of target response with Dmin was found 

(odds ratio (OR) = 4.3) at the cutoff dose of 8.7 Gy. Furthermore, the Dmin 

seems to differentiate well the two patient groups since in a ROC analysis 

it gives the area under the ROC curve = 0.69. Finally, it is found that documented 

target response rate increases with minimum target dose.

S 298 CLINICAL/DISEASE SITES : OTHERS 

Conclusions: It is shown that the response group receives larger average 

minimum dose than the non-response group. The minimum dose of 8.7 Gy 

can be considered as a primary threshold above which the probability of having 

target response increases considerably. In the future, a maximum likelihood 

fitting will be used to determine the parameters characterizing the doseresponse 

relation of acoustic neuromas. 

935 poster 

DOES THYROID STUNNING OCCUR IN PATIENTS TREATED WITH 

I-131 FOR HYPERTHYROIDISM? 

E. Forssell-Aronsson 1 , C. Lundh 1 , U. Lindencrona 1 , J. Himmelman 1 , A. 

Lundström 1 , G. Berg 2 

1 

GÖTEBORG UNIVERSITY, SAHLGRENSKA UNIVERSITY HOSPITAL, Radiation 

Physics, Gothenburg, Sweden 

2 

GÖTEBORG UNIVERSITY, SAHLGRENSKA UNIVERSITY HOSPITAL, Oncol- 

ogy, Gothenburg, Sweden 

Purpose: Thyroid stunning is discussed mainly regarding thyroid carcinoma 

patients undergoing radioiodine treatment. The extent of the effect varies 

among published studies. Attempts have been made to identify the highest 

absorbed dose that does not cause stunning. Previously, we showed that 

stunning was evident in primary cultured porcine thyrocytes exposed to 0.15 

Gy from 131I. If this result is applicable in vivo, stunning would be found 

also in hyperthyroid patients receiving 131 I therapy, since the absorbed dose 

from the diagnostic amount of 131 I is typically 0.1-0.3 Gy. Therefore, we investigated 

whether thyroid stunning could be identified in patients receiving 

radioiodine treatment for benign thyroid disease. 

Materials: Nineteen patients diagnosed with Graves’ disease or toxic nodular 

goiter who received 131 I treatment were included in the study. Uptake measurements 

were performed one and six days after administration of both diagnostic 

(0.45-0.62 MBq) and therapeutic (200-620 MBq) amounts of 131 I was 

determined. The ratio between the percentage uptake of therapeutic and diagnostic 

amounts of 131 I was calculated. The estimated effective half-life and 

the absorbed dose delivered per unit activity administered were determined 

for both administrations of 131 I. Serum levels of antibodies against thyroperoxidase 

and TSH receptor were determined. 

Results: Large individual variations in 131 I uptake after therapy compared 

to after diagnostics were evident. In 26% (day 1) and 47% (day 6) of the 

patients, the percentage uptake was lower at therapy than at diagnostics, 

indicating possible stunning. Uptake was higher at therapy in 37% (day 1) and 

26% (day 6) of the patients. No correlations between the change in uptake 

and absorbed dose at diagnostics or at therapy were observed. There was a 

statistically significant correlation between the absorbed dose from diagnostic 

131 I and the change in estimated effective half-life from diagnostics to therapy 

and also the change in absorbed dose per unit activity administered at therapy 

compared to at diagnostics. No overall changes in effective half-life or uptake 

for diagnostic or therapeutic administration of 131 I were detected. 

Conclusions: The statistically significant negative correlation between absorbed 

dose from diagnostic 131 I and the change in estimated effective halflife 

as well as the change in absorbed dose delivered per unit activity suggest 

thyroid stunning. Further studies are needed to establish a connection between 

absorbed dose, time, and stunning, for low absorbed doses such as 

those administered for hyperthyroidism. 

936 poster 

FIRST TOXICITY REPORT OF THE BC2001 TRIAL; A MULTICENTRE 

PHASE III RANDOMISED TRIAL OF RADIOTHERAPY WITH AND 

WITHOUT SYNCHRONOUS CHEMOTHERAPY IN MUSCLE INVA- 

SIVE BLADDER CANCER ISCRTN NO. 68324339, EUDRACT NO. 

2004-000164-26. 

N. James 1 , S. Hussain 1 , C. Rawlings 2 , P. Jenkins 3 , J. Tremlett 4 , M. 

Crundwell 5 , R. Huddart 6 , E. Hall 7 , S. Rogers 7 

1 

UNIVERSITY OF BIRMINGHAM, CRUK Institute for Cancer Studies, 

Birmingham, United Kingdom 

2 

SOUTH DEVON HEALTHCARE NHS TRUST, Department of Radiotherapy, 

Torquay, United Kingdom 

3 

CHELTENHAM GENERAL HOSPITAL, Glocestershire Oncology Centre, 

Cheltenham, United Kingdom 

4 

SUSSEX CANCER CENTRE, Department of Radiotherapy, Brighton, United 

Kingdom 

5 

ROYAL DEVON & EXETER HOSPITAL NHS FOUNDATION TRUST, Department 

of Urology, Exeter, United Kingdom 

6 

THE INSTITUTE OF CANCER RESEARCH, Clinical Academic Radiotherapy, 


7 

THE INSTITUTE OF CANCER RESEARCH, Clinical Trials and Statistics Unit, 


Purpose: The BC2001 trial was set up to address whether the use of concomitant 

chemotherapy could improve loco regional control and whether radiotherapy 

volume modification could reduce late toxicity without detriment to 

tumour control. The trial was designed to assess initial toxicity, toxicity during 

treatment, and then at six months, twelve months and annually thereafter according 

to the CTC, RTOG and Lent/Som scales. The trial closed to accrual 

on 30/04/2008. This is the first report of this trial focusing on acute toxicity. 

Materials: BC2001 was a multi-centre phase randomised phase III trial utilising 

a 2x2 design. Patients were randomised to one or both of two randomisations: 

1. radiotherapy alone (RT) or with 5-fluoruracil (5FU) (500mg/m2 daily 

for 5 days as continuous infusion weeks 1 and 4) and mitomycin C (MMC) day 

1 (chemoRT); 2. radiotherapy to the tumour and whole bladder or a 2-stage 

technique reducing dose to uninvolved bladder to 85%. 

Results: The initial summary analyses have been made for the purposes of 

this abstract; a full clinical trial analysis will be presented at the meeting. At 

the time of trial closure 352 patients had been recruited to the chemoradiotherapy 

comparison, with 175 patients randomised to chemoRT. Median age 

was 73 (IQR 54-84) years, 80% male, WHO performance status (0) 57%, (1) 

37%, (2) 6%. Patients were well balanced with respect to age, stage and 

performance status. Haematological toxicity during treatment: 12 chemoRT 

patients suffered grade 3 or 4 haemotological toxicities versus 7 RT patients. 

Non-haematological toxicity: there were 15 grade 3 toxicities in the chemoRT 

arm compared with 12 grade 3 and two grade 4 toxicities in the RT only arm. 

We have 6 month follow up data on 197/352 patients: 9% of chemoRT patients 

have grade 3/4 toxicity versus 3% of RT only patients. The remaining 

patients in both arms had maximum toxicity grade 0-2. 

Conclusions: In keeping with our previous phase I and II trials, chemoRT 

with 5FU/MMC was well tolerated with modest increases in reported toxicity 

compared to RT only. We will present a fuller analysis at the meeting including 

delivered dose intensity and a detailed breakdown of patterns and duration of 

toxicity. 

937 poster 

FRACTIONATED CYBERKNIFE RADIOSURGERY FOR UVEAL 

MELANOMA 

U. Selek 1 , F. Zorlu 1 , H. Kýratlý 2 , A. Dogan 1 

1 



2 

HACETTEPE UNIVERSITY, FACULTY OF MEDICINE, Department of Ophtal- 

mology, Ankara, Turkey 

Purpose: To evaluate prospectively local tumor control and morbidity after 

fractionated Cyberknife radiosurgery for uveal melanoma, unsuitable for 

ruthenium-106 brachytherapy or local resection. 

Materials: Cyberknife radiosurgery was offered only to patients with uveal 

melanoma who were deemed unsuitable for ruthenium-106 brachytherapy or 

local resection. This study includes: (1), melanoma of ≥7 mm in initial height; 

or (2), juxtapapillary and/or juxtamacular tumors (height, ≥3 mm; posterior 

tumor magrin extending to 3 mm of optic disk rim and/or fovea). In these 

cases, episcleral ruthenium-106 brachytherapy is complicated by a increased 

rate of local tumor control failures and radiation-induced side-effects. Patients 

were excluded if they presented evidence of echographic extrascleral tumor 

extension, neovascular glaucoma, or any form of pretreatment or metastases 

at baseline. The eye was stabilized by peribulbar injection of 5 cc 2% lidocaine 

while the patient is staring. CT-scans with a 1 mm slice thickness were 

obtained for planning. Cyberknife radiosurgery is performed to a total dose 

of 60 Gy to 70% or 85% isodose line in 3 fractions (20 Gy/fraction). PTV for 

Cyberknife is the contrast-enhancing lesion demonstrated on MRI plus a 1 

mm margin. 

Results: Four patients with uveal melanoma were treated in this protocol. All 

patients had serous retinal detachment accompanied with the tumor. None 

of the potential grade ≥2 acute toxicities were observed. One month follow 

up revealed no progression of disease with stabile mass in all patients and 

improvement of retinal detachment in three patients and increment in one. 

Longer follow up is required for further recommendations.

Conclusions: Cyberknife fractionated radiosurgery appears to be an effective 

local treatment in uveal melanoma with no serious acute side effects. 

938 poster 

INFLUENCE OF I.V. CONTRAST AGENT ON DOSE CALCULATION IN 

3D-TREATMENT PLANNING FOR RADIOSURGERY OF CEREBRAL 

ARTERIOVENOUS MALFORMATIONS 

A. Zabel-du Bois 1 , B. Ackermann 1 , S. Milker-Zabel 1 , H. Hauswald 1 , O. 

Schramm 1 , G. Sroka-Perez 1 , P. Huber 2 , J. Debus 1 

1 

UNIVERSITY OF HEIDELBERG, Radiooncology and Radiotherapy, Heidelberg, 

Germany 

2 

GERMAN CANCER RESEARCH CENTER (DKFZ), Radiation Therapy, 


Purpose: For radiosurgery (RS) in cerebral arteriovenous malformations 

(AVM) accurate contouring of the target volume is recommended. Therefore, 

the application of i.v. contrast agent is needed to outline the nidus during 

the computed tomography (CT) scans. In order to calculate the dose from 

CT scans the Hounsfield units (HU) are converted into the corresponding 

electron densities. Due to the high atomic number of contrast agent a certain 

overdosage is expected. We investigate the influence of local density 

increase by i.v. contrast agent on dose calculation in three-dimensional (3D)treatment 

planning for RS of cerebral AVM. 

Materials: For 3D-treatment planning all CT images were transferred to the 

STP 3.0 software (Stryker-Leibinger, Freiburg, Germany). Linac-based RS 

was performed using a total number of 9 to 14 isocentric, non-coplanar, irregulary 

shaped beams. An estimation of dose deviation was calculated from the 

data sets of 30 patients using the published equation for 6 MeV photons. Additionally, 

we used the enhanced and unenhanced data sets of 10 patients for 

exact analysation of dose deviation. Dose calculation was performed using 

the same RS treatment plan on both data sets. Both plans were standardized 

to 1 Gy at isocenter with the same dose weight for all beams. 

Results: Mean target volume was 5.3 cc (range, 0.1-41.2 cc). Mean maximum 

diameter of target was 23.2 mm (range, 8-51 mm). Mean difference 

of HU (dHU) between enhanced and unenhanced CT was 152 HU (range, 

50-350 HU). The estimated dose deviation was 1/3 -15(34%); Histology: NSI-33,NSII-9,MC-2 

Non Hodgkin Lymphoma: Age:mean(range)-20-32 (26) ;2-breast DLBCL,1brain 

DLBCL 2-mediastinal DLBCL; Treatment: Hodgkin Lymphoma I 

trimester: therapeutic abortion-6, radiotherapy(IF)-2, miscarriage(7Hbd)-1 ; 

II trimester: radiotherapy (IF-total dose 30-35 Gy) and chemotherapy regimen 

EVA(2cycles)before delivery-2; chemotherapy EVA(3-4 cycles)before 

delivery and radiotherapy after delivery-16 radiotherapy(IF-total dose between 

20-44 Gy)before delivery and chemotherapy LOPP,MOPP,MOPP/ABV 

after delivery -5; In vivo dosimetry of testes during radiation treatment by irregular 

fields- supradiaphragmatic lymph node. Thermoluminescent dosimetry 

and individually blocks of the abdomen were used. The dose to the fetus 

was estimated individually in all. III trimester-method "watch and wait"-12 

patients NHL-individual therapy 

Results: Hodgkin Lymphoma: Live with CR/CRu-37 (20-206 months after 


S 299 

therapy),PR 2 patient PD-7(3-72 months after CR), Live with PD-1 after PB- 

SCT, Death with PD -4 Children(age)-35 (3 month-20 years); Non-Hodgkin 

Lymphoma: Live with CR/CRu-2(39-58 months after therapy ); Death with 

PD-2 (12-94 months after delivery); Live after abortion and chemotherapy 

protocol GMALL before radiotherapy -1; Children(age)4 -(2-9 years); In all 

cases of studied children ,physical, neurological psychological, hematological 

functions are normal. One infant developed acute respiratory distress 

syndrome and died 6 days after delivery 

Conclusions: Treatment requires individualization to insure that the patient 

will be cured and fetus protected. The group of pregnant woman with NHL 

had a poorer overall prognosis compared with the group with HL. 

940 poster 

PROGNOSTIC FACTORS IN PATIENTS WITH ENDOMETRIAL 

CANCER TREATED WITH SURGERY AND POSTOPERATIVE 

RADIOTHERAPY 

B. Lindner 1 , R. Krynicki 1 , W. Michalschi 2 , J. Jonska-Gmyrek 1 , J. 

Staniaszek 1 , M. Niemec 1 

1 

MARIA SKLODOWSKA-CURIE MEMORIAL CANCER CENTER, Radiotherapy 

, Warsaw, Poland 

2 

MARIA SKLODOWSKA-CURIE MEMORIAL CANCER CENTER, Biostatistic, 

Warsaw, Poland 

Purpose: To assess the prognostic factors in endometrial cancer. 

Materials: Material consisted of 880 patients with FIGO stage I-III endometrial 

cancer treated between 1992-1998 with total hysterectomy and adjuvant 

radiotherapy. The median follow-up time for leaving patients was 9 years, 

range 0,5-13 years. The multivariate Cox’s analysis of prognostic factors for 

overall survival was carried out. The following variables were analyzed: stage 

of the disease; histopatological type of the tumor; grade; depth of the invasion 

of myometrium (≤ 50% vs. > 50%); WHO performance status (0 vs ≥1); 

the hormonal activity status (pre- or postmenopausal); coexistence of obesity, 

hypertension and diabetes; interval between hysterectomy and radiotherapy 

(≤ 74 vs > 74 days). 

Results: The following variables were negatively associated with overall survival: 

long time interval between surgery and radiotherapy, hazard ratio (HR) 

1,33 (95 % confidence interval (CI) 1,01;1,75 (p=0.040); advanced stage 

of disease HR 2,8 CI 2,05;3,81 p

S 300 CLINICAL/DISEASE SITES : OTHERS 

of achieving CD4+/CD8+ T cell count ≤ 10% of baseline. Donor specific cytotoxic 

antibodies were eliminated with i.v immunoglobulins & plasmapharesis 

before RTx. Immunosuppression was withdrawn 3-6months after RTx for patients 

with consistently positive chimerism. Robust tolerance was defined 

as stable allograft function for >100 days without immunosuppression. Prope 

tolerance was defined as early adequate, stable grafts function with no rejection 

episodes on minimum immunosuppression. Metastable tolerance was 

adequate graft function on immunosuppression with single episode of steroid 

responsive acute rejection. 

Results: 

Conclusions: The safe & effective dose for tolerance induction in LRD renal 

transplantation is 1000 cGy. 

942 poster 

RADIATION THERAPY ON LEFT THORACIC AN CHEMOTHERAPY 

ANTHRACYCLINE-CONTAINING: TRANSIENT ELECTROCARDIA- 

GRAPHIC ABNORMALITIES AND PERSISTENT SCINTIGRAPHIC 

PERFUSION DEFECTS 

G. Gallucci 1 , M. Coccaro 2 , A. Nappi 3 , S. Clemente 4 , V. Fusco 5 

1 

ONCOLOGICAL HOSPITAL, Department of Cardiology, Rionero in Vulture 

(Pz), Italy 

2 

ONCOLOGICAL HOSPITAL, Oncology Unit, Rionero in Vulture (Pz), Italy 

3 

ONCOLOGICAL HOSPITAL, Neclear Medicine, Rionero in Vulture (Pz), Italy 

4 

ONCOLOGICAL HOSPITAL, Medical Physics, Rionero in Vulture (Pz), Italy 

5 

ONCOLOGICAL HOSPITAL, Radioterapy Oncology, Rionero in Vulture (Pz), 

Italy 

Purpose: Radiation Therapy (RT) to the thorax and anthracycline-based 

chemotherapy (CHT) play an important role in the multimodality management 

of patients with breast cancer. Although modern RT techniques have reduced 

radiation exposure to the heart, they may not have eliminated cardiotoxicity. 

It appears that contemporary RT methods to the left brest may still cause 

cardiovascular disease. Changes in myocardial perfusion, wall motion and 

ejection fraction have been demonstrated in patients undergoing radiation 

treatment. To evaluate post-radiation regional heart changes from tangential 

photon beam RT, we have examined the surrogate endpoints of electrocardiographic 

(ECG) change and single photon emission computed tomography 

(SPECT) cardiac perfusion after RT. 

Materials: 10 patients (mean age 44 affected by left side ductal infiltrating 

carcinoma of the breast) were treated with neoadjuvant CHT (epyrubicine 75 

mg/m2 and taxol 175 mg/m2) every 3 weeks for 4 cycles, surgical mastectomy, 

adyuvant CHT (CMF 1-8 given every 3 weeks for 6 cycles) and RT 

(total dose of irradiation was 60Gy). 

Results: Before surgery 12 lead ECG were normal. Six months after RT their 

12 lead ECG showed marked abnormalities of ventricular repolarization mimicking 

anterior myocardial ischemia with ST elevation in V2-V3 and negative 

T waves in D1, a VL, V2-V6 without both symptoms and echocardiographic 

abnormalities of left ventricle (LV) wall motion. SPECT myocardial perfusion 

scintigraphy showed reversible perfusion defects in distal anterolateral and 

anteroseptal region of the LV and a fixed perfusion defect in the apical region 

possibly due to attenuation from breast prothesis. We put them on ASA 

and betablockers. After 3 months, their ECG was unchanged. After 1 year 

while their ECG are normal, myocardial perfusion defects in distal anterolateral 

and anteroseptal region of the LV are still present. The patiens are still 

asymptomatic and scheduled for a long follow-up. 

Conclusions: We recommend frequent cardiac monitoring of patients submitted 

to anthracycline-based CHT and to left side wall RT because recognition 

of the relationship between RT and CAD may lead to a better understanding 

of the clinical impact of these abnormalities, to a quantitative definition of 

the need for more intensive investigations and to an earlier intervention. 

943 poster 

RADIATION-INDUCED PLEXOPATHY: SIGNIFICANT NEUROLOGI- 

CAL SYMPTOMS REGRESSION BY A PENTOCLO COMBINATION IN 

A PHASE II TRIAL. 

S. Delanian 1 , P. F. Pradat 2 , R. Porcher 3 , T. Maisonobe 4 , J. L. Lefaix 5 

1 

HÔPITAL SAINT LOUIS, AHHP, Department of Oncology-Radiotherapy, 

Paris, France 

2 

HÔPITAL PITIÉ SALPÉTRIÈRE, APHP, Fédération de Neurologie, Paris, 

France 

3 

HÔPITAL SAINT LOUIS, APHP, Département d, Paris, France 

4 

HÔPITAL PITIÉ SALPÉTRIÈRE, APHP, Fédération de Neurophysiologie 

Clinique, Paris, France 

5 

COMMISSARIAT À L’ENERGIE ATOMIQUE, Caen, France 

Purpose: Radiation-induced peripheral neuropathy (RIP) is a rare and severe 

delayed complication of radiotherapy that is spontaneously irreversible, 

characterized by a triad combining demyelization, axonal degeneration and 

fibrosis. There is currently no medical treatment to limit or reduce symptoms 

[1]. We previously described a successful long term use of combined pentoxifylline 

-tocopherol (PE) in RI superficial fibrosis [2]; and PE- clodronate 

(Pentoclo) in osteoradionecrosis [3]. In a series of patients treated with 

PE for superficial fibrosis including 8 patients who suffered with combined 

brachial plexopathy after breast cancer irradiation, we observed 4/8 neurological 

symptoms stabilisation but no improvement at 18 months. 

Materials: For last ten years, 93 patients were seen for RIP at Saint Louis 

Hospital. Fifty assessable patients, with partial PRI of upper limb (32 cases) 

or lower limbs (18 cases) for mean seven years, 20 yrs after RT for breast 

cancer or Hodgkin disease (exclusion for analysis if complete motor deficit, 4 

limbs, immediate lost of follow-up) were treated by a daily oral PENTOCLO 

combination using pentoxifylline (800mg)- tocopherol (1000mg)- intermittent 

clodronate (1600mg/d; 5 days/7), alternated with prednisone (20 mg/d; 2 

days/7). The main endpoint was a neurological score/ 20 adapted from SOMA 

95// CTAEv3.0 2003// NCI.CTC 99// INCAT 2000 scales with pain/5, sensory/5, 

motor/10. Clinical assessment and EMG were done every 6 months 

during 5 years: mean initial score Mo was 11 ±3 [range 5-16]. 

Results: Treatment was well tolerated. Pentoclo was continuously effective 

over several years and resulted in a significant progressive neurological score 

improvement (p

on residual disease. 2) Voxel dose probability, which describes the chance 

that a voxel actually receives a certain dose given a planned dose distribution. 

This is needed to adapt the multi-dose level treatment plan to make it robust to 

planning uncertainties without using margins...In practice we will compute a 

Dynamic Probability with a confidence interval for each voxel of interest. Our 

simulations show that this is feasible (see Figure). 3) Verification of the actual 

delivered cumulative dose using 3D in vivo dosimetry and taking advantage 

of non-rigid deformation models. (van Elmpt et al.; Fekkes et al.). Further 

refinements of this approach are possible by taking into account the effect of 

systemic treatments and other biological and genetic factors. We emphasise, 

however, that a great deal of research and clinical studies are needed before 

this can be realised in clinical practice. 

Conclusions: Voxel Control/ Complication Probability is a quantitative, flexible 

model that may allow personalised radiation alone or combined with drugs 

and takes advantage of tumour and normal tissue heterogeneity. 

945 poster 

SELECTION OF THYROID CANCER PATIENTS FOR THERAPEUTIC 

DOSES OF RADIOIODINE - CAN STIMULATED THYROGLOBULIN 

LEVELS AFTER IODINE 131 ABLATION PREDICT FOR THE NEED 

FOR SUBSEQUENT DOSES OF IODINE 131? 

S. Cherian 1 , R. Benson 1 , L. Tan 1 , S. Jefferies 1 

1 CAMBRIDGE UNIVERSITY HOSPITALS NHS FOUNDATION TRUST, Oncology, 


Purpose: In patients with differentiated thyroid cancer, British Thyroid Association 

guidelines recommend a diagnostic whole body iodine scan (WBS) 

6 months after I 131 ablation. Patients with positive scans then proceed to a 

therapy dose of I 131 . This policy avoids unnecessary treatment in some patients, 

thus minimising the risk of second malignancies. However, patients 

have to endure symptoms of hypothyroidism from thyroxine withdrawal twice 

(for WBS and subsequent therapy dose). In selected high risk patients, therefore, 

our policy is to omit WBS and proceed directly to the therapy dose. This 

audit evaluates the use of stimulated thyroglobulin (sTg) levels at the time 

of initial ablation to improve patient selection for subsequent therapy dose 

without diagnostic WBS. 

Materials: 58 consecutive patients underwent I 131 ablation between June 

04 and May 06 for differentiated thyroid cancer. sTg levels and WBS were 

obtained at the time of ablation. Patients considered low risk (based on age, 

sex and stage) proceeded to diagnostic WBS at 6 months whilst high risk 

patients proceeded to therapy I 131 dose with WBS and sTg at the time of 

therapy. 

Results: 19 patients were excluded from the analysis with negative scan and 

sTg (2), anti Tg antibodies (1) and missing sTg results (16). Of the remaining 

39 patients, 29 were female and 10 male. 14 patients (35.9%) had diagnostic 

WBS at 6 months while 25 patients (64.1%) received therapy I 131 . Of the 14 

patients who had diagnostic WBS, WBS was negative in 12 patients (85.7%) 

and positive in 2 (14.3%). Of the 25 patients who had therapy I 131 , 16 (64%) 

had positive scans or detectable sTg at the time of therapy. 9 patients (36%) 

had negative scans and undetectable sTg at the time of therapy and could 

be considered to have had unnecessary treatment. 7 patients had sTg > 50 

mcg/l at the time of ablation, all of whom had positive scans and/or detectable 

sTg at the time of subsequent therapy I 131 . 12 patients had sTg > 10 mcg/l 

at the time of ablation, 10 of them had detectable sTg at subsequent therapy 

I 131 . The sTg of the two that became undetectable was 18.8 and 40.9 mcg/l. 

Conclusions: Using a post ablation threshold sTg > 10 mcg/l to select patients 

for subsequent I 131 therapy could optimise patient selection for subsequent 

radioiodine. This would minimise the number thyroxine withdrawals 

for higher risk patients and decrease the risk of over-treatment in lower risk 

patients. 

946 poster 

THE RELATIONSHIP BETWEEN RADIOTHERAPY DELAY AND 

LOCAL RECURRENCE 

D. Sutton 1 , Z. Chen 1 , W. Kong 1 , S. Keller 1 , J. P. Voroney 1 , W. MacKillop 

1 

1 QUEEN’S UNIVERSITY CANCER RESEARCH INSTITUTE, Cancer Care and 

Epidemiology, Kingston, Ontario, Canada 

Purpose: There has been variation in the results of studies examining the 

effect of radiotherapy (RT) delay on clinical outcomes. The purpose of this 

study was to synthesize the most recent clinical evidence relating RT delay to 

the risk of local recurrence. 

Materials: We updated a systematic review of all papers published between 

1975-2005 to include papers published between 2005-2007 using PubMed, 

HealthStar, and the Cochrane Library databases. Only high quality (HQ) studies 

that properly controlled for confounding factors were included in our primary 

analysis. 

Results: Our combined search yielded 42 relevant papers, of which 22 met 

our HQ criteria. Meta-analyses of the 22 HQ papers on local recurrence 

showed evidence of increased risk from RT delay: RR local recurrence/month 


S 301 

= 1.12, 95%CI= 1.07, 1.18. For post-operative breast radiation, the RR local 

recurrence/month =1.09, 95%CI= 1.02, 1.16. For definitive head and neck 

radiation, the RR local recurrence/month =1.15, 95%CI= 1.02, 1.29, and 

for post-operative head and neck radiation, the RR local recurrence/month 

=1.19, 95%CI=1.08, 1.31. Meta-analyses of all 42 relevant papers produced 

similar findings to those in our primary analysis: RR local recurrence/month 

= 1.12, 95%CI= 1.07, 1.16. 

Conclusions: RT delay is associated with an increased risk of local recurrence. 

This association is strongest in head and neck cancer patients. Waiting 

time for RT should be as short as reasonably achievable. 

947 poster 

TREATMENT WITH GLUTAMINE DURING RADIOTHERAPY ON 

PELVIC AREA. INITIAL RESULTS 

I. Membrive Conejo 1 , A. Reig 1 , M. Algara 1 , P. Foro 1 , J. Sanz 1 , N. 

Rodriguez 1 , J. Lozano 1 , J. L. Lopez 1 , J. Dengra 1 

1 HOSPITAL DE L’ESPERANÇA, Radiotherapy, Barcelona, Spain 

Purpose: Diverse studies conclude that administration of glutamine during 

treatment with radiotherapy has a protective action on mucosa decreasing 

incidence of the inflammatory effect of the radiation or delaying toxicity. Mainly 

the benefit has been demonstrated in protection of esophageal mucosa and 

small bowel. The objective was to know if the administration of glutamine 

during radiotherapy treatment in pelvis has a good tolerance and if there are 

a decrease in the incidence of small bowel or rectum toxicity. 

Materials: Every patient received prophylactic glutamine powder in doses of 

10 g/8 h 10 days before the beginning of the treatment with pelvic radiotherapy 

and up to 10 days after the end. We registered the G-I toxicity (enteritis 

and proctitis) and the dose of radiation administered to the patient at the beginning 

of toxicity. RTOG toxicity criteria was used to evaluate the G-I toxicity. 

The toxicity was assessed only during the time of treatment on pelvic area, 

without including the toxicity during the boost treatment. 

Results: 27 patients were included in the study, mean age was 64.29 years. 

There were 10 (37 %) with cervix carcinoma, 11 (40.7 %) with endometrial 

carcinoma and 6 (22.3 %) with rectal carcinoma. In 11.5 % an abdominal 

surgery was performed and then chemotherapy, 29.6 % only with chemotherapy, 

44.4 only with surgery and in 7.5 % nor surgery nor chemotherapy. The 

type of chemotherapy was 5-Fluorouracil in 46.2 % of the patients and cisplatine 

in 53.8 %. The average dose of radiotherapy administered on the pelvis 

was 45.29 Gy with 1.8-2 Gy/fraction. We excluded 1 patient because bad tolerance 

to glutamine (nauseas and vomits after the ingestion) The registered 

toxicity was (stratified in groups): 

Conclusions: We conclude that acute gastrointestinal toxicity during treatment 

of pelvic radiotherapy with administration of glutamine is similar to the 

habitual toxicity in our center. In our study the toxicity has been gathered 

during the pelvic treatment up to 45-46 Gy, in next studies we have to verify 

if the protective effect of glutamine is demonstrated with higher doses of radiation. 

Glutamine was well tolerated, only 1 patient has been excluded from 

the study by adverse effects.

S 302 CLINICAL/DISEASE SITES : PAEDIATRICS 

Clinical/Disease sites : Paediatrics 

948 poster 

20 YEARS OF EXPERIENCE IN THE TREATMENT OF EWING 

SARCOMA IN CHILDREN 

J. Vízkeleti 1 , B. Kocsis 1 , G. Fröhlich 1 

1 NATIONAL INSTITUTE OF ONCOLOGY, Radiotherapy, Budapest, Hungary 

Purpose: To evaluate the results and the side effects of radiotherapy for infants 

with Ewing sarcoma. 

Materials: Between 1987 and 2007 60 children (aged 4-19 years) with Ewing 

sarcoma were subjected to radiotherapy in our Department. The baseline 

clinical and treatment caracteristics were reviewed. The median follow up of 

survivor patients was 149 months. 

Results: The total crude rate of local recurrence or distant metastases was 

34.5% or 58% respectively. The crude rate of cause specific death was 60%, 

and the median survival time was 84 months (range 8-236). We found a 

corellation between the age of the patient and the survival time. None of the 

survivig patients developed second primary. 

Conclusions: Older age has a negative influence on survival time. Patients 

can be considered cured at 6 years after radiotherapy. 

949 poster 

CASE REPORT: PROTON RADIATION THERAPY FOR SECONDARY 

ATYPICAL LUMBAR MENINGEOMA ARISING 25 YEARS AFTER IN- 

TERDISCIPLINARY TREATMENT FOR ADVANCED WILMS TUMOR 

B. Pehlivan 1 , H. P. Rutz 1 , G. Goitein 1 , K. Haller 1 , A. Lomax 1 , E. Hug 1 , 

B. Timmermann 1 

1 PAUL SCHERRER INSTITUTE, Center for Proton Radiation Therapy, Villigen 

- PSI, Switzerland 

Purpose: To report a case treated with spot scanning proton radiation therapy 

(PT) for progressive lumbar meningeoma WHO grade II in a survivor of 

Wilms tumor in childhood. 

Materials: At the age of 1 year (1974), the female patient was diagnosed 

with stage V Wilms tumor originating in the right kidney with metastasis to: 

the contralateral kidney and lungs. She was treated with resection of the right 

kidney, partial resection of the left kidney and triple resection of pulmonary 

metastasis followed by chemotherapy (Actinomycin D) and involved field radiation 

therapy (30 Gy). She remained tumor free for the next 25 years (until 

1999) when she presented with symptoms of cauda equina compression at 

the level of L1 to L2. She underwent surgical decompression. Histologically, 

meningeoma WHO grade I was diagnosed. She underwent two additional 

subsequent resections, one in 2000 and one in 2001 for symptomatic tumor 

progression. In 2002, she had yet another cauda equina compression, this 

time at the level of L3 to 4. Partial resection revealed atypical meningeoma 

WHO grade II. She remained symptomatic (pain) and was referred for PT. 

We treated her to a doses DRBE (conversion factor: 1.1) of 68.5 Gy to cauda 

equina (L1 to L4). Treatment was delivered in 4 daily fractions of 1.8 Gy per 

week. The patient was irradiated in the prone position. Dose to ovaries was 

below 0.1%. Maximal dose to the hypertrophic remaining left kidney (228 ml) 

was 45.4% (15.2 ml or 6.6% received a dose of ≥1%, 4.6 ml or 2% a dose of 

≥5%). We will present the results of an ongoing planning dose comparison 

(PT as delivered vs. IMRT) and comment on organ at risk and integral doses. 

Results: Within 3 weeks of initiating PT, pain began receding. After 7 weeks, 

she was pain free. In the irradiated skin, a grade 2 reaction developed temporally. 

On follow-up MRIs, residual tumor resolved within 6 months and the 

patient remained in remission thereafter. In 2004 (14 months after PT) and 

2006 (27 months after PT) she gave birth to two healthy boys. At the writing 

of this report, she is working (80% activity) as a highly qualified professional. 

She has no neurological or other complaint. 

Conclusions: The general claim that proton irradiation reduces unwanted 

dose load to non-target tissues is underlined by this case. It illustrates the 

normal tissue sparing capability of PT not only for defined organs at risk; 

the use of PT allowed here to effectively sparing pre-irradiated tissues from 

unnecessary re-exposure, even though the exact limits of the earlier target 

volumes were unknown. 

950 poster 

INTENSITY MODULATION RADIOTHERAPY IN THE TREATMENT 

OF PAEDIATRIC NEUROBLASTOMA 

M. Piergentili 1 , F. Foppiano 2 , S. Garelli 1 , S. Barra 1 

1 NATIONAL INSTITUTE FOR CANCER RESEARCH, Genova, Italy 

2 ASL 5, La Spezia, Italy 

Purpose: Our purpose is to understand how useful IMRT can be in paediatric 

radiotherapy in comparison with traditional 3D conformational technique for 

irradiation of paravertebral disease. 

Materials: Four patients who received radiotherapy for abdominal neuroblastoma 

at our institution were identified. All of them were male and the mean 

age at radiotherapy treatment was 2.6 yrs (range 1.9-2.9). Three patients had 

stage IV disease and one was a relapse. All patients presented paravertebral 

disease between D7 and L1 vertebrae. RT dose was 2100cGy/150cGy/14 

fractions for all the patients.We prepared conformal 3D and IMRT treatment 

plans to evaluate which was the best solution. In the elaboration of the 

plans our goals were: homogeneous vertebral irradiation and kidney sparing. 

We considered different IMRT techniques: IMRT with 4 and 7 radiation 

fields and we compared plans with different beam energies: 6MV and both 

6MV and 15MV. We used the same constraints for all the patients and for 

all the IMRT techniques used: kidney: V16Gy

952 poster 

CLINICAL/DISEASE SITES : PALLIATION/SUPPORTIVE CARE/PATIENT SUPPORT 

RISK ESTIMATION OF RADIATION-INDUCED THYROID CANCER 

FROM TREATMENT OF SUPRA-DIAPHRAGMATIC HODGKIN’S 

DISEASE IN CHILDREN 

A. Tzedakis 1 , M. Mazonakis 1 , J. Stratakis 2 , S. Kachris 2 , E. Lyraraki 2 , A. 

Fasoulaki 2 , E. Petinelly 2 , H. Varveris 2 

1 

UNIVERSITY HOSPITAL OF HERAKLION, Medical Physics, Heraklion, 

Greece 

2 

UNIVERSITY HOSPITAL OF HERAKLION, Radiation Oncology, Heraklion, 

Greece 

Purpose: To estimate the thyroid dose and the associated risk for cancer 

induction resulting from supra-diaphragmatic radiotherapy for Hodgkin’s disease, 

during childhood. 

Materials: The MCNP5 Monte Carlo code was used to simulate a 6 MV 

linear accelerator photon beam. Mathematical anthropomorphic phantoms 

generated by BodyBuilder software (White Rock Science, White Rock, NM, 

USA) were employed to represent the average individuals of 5, 10, and 15 

years old. Anterior and posterior field irradiations in the region of mediastinum 

were simulated. The shielding of lung structures was modeled with 6-cm-thick 

lead blocks placed on a Lucite tray. The mean thyroid dose was calculated. 

Monte Carlo calculations were verified by directly measuring thyroid dose on 

a physical phantom simulating a 10-year-old individual using thermoluminescent 

dosimeters. The risk for thyroid tumor induction was assessed using 

appropriate risk coefficients suggested by ICRP and NCRP. 

Results: For a prescribed tumor dose of 20 Gy, the thyroid dose was found 

to vary with respect to patient age. For subjects of 5-, 10-, and 15-years old, 

the thyroid dose was 310, 410 and 449 mGy, respectively. The consequent 

risk for thyroid cancer development was 233, 308 and 337 (X10 -5 ) for 5-, 10-, 

and 15-years old patients, respectively. The percentage differences between 

Monte Carlo calculated and TLD measured organ doses were less than 14.5 

%. 

Conclusions: Radiotherapy for supra-diaphragmatic Hodgkin’s disease in 

children can result in an increased risk for development of thyroid malignancies. 

The presented data may be of value for estimating the mean thyroid 

dose and the associated risk for induction of secondary thyroid malignancies 

from supra-diaphragmatic radiotherapy. 

953 poster 

TOTAL BODY IRRADIATION IN PAEDIATRIC PATIENTS: ROLE OF 

EQUIVALENT UNIFORM DOSE IN TREATMENT EVALUATION 

E. Madon 1 , A. Mussano 1 , U. Monetti 1 , S. Gribaudo 1 , A. Sardo 1 , V. 

Richetto 1 , A. Urgesi 1 

1 OIRM S.ANNA, Radiation Oncology, Torino, Italy 

Purpose: Total body irradiation is a fundamental component of bone marrow 

transplantation (BMT) in most malignant and many genetic disease states. 

The target volume encompasses the entire body that should be irradiated 

with homogeneity. Dose information are generally incomplete if based only 

on in vivo dosimetry. To supply this physical deficiency, dose calculation has 

been performed on TC images that should include the entire body: this can be 

possible with paediatric patients without long acquisition time. With modern 

TPS it’s possible to calculate dose volume histogram on different organ and 

achieve good information on physical and biological dose on tissues. The 

purpose of this study is to analyse correlation between dose information and 

treatment effects. 

Materials: 23 patients (11 M, 12 F, median age 10) referred to our department 

for TBI before BMT were enrolled in the study. All pts received 2 Gy 

administered twice daily to a total dose of 12 Gy. For infants and small children 

(6 pts) an anterior/posterior set up with a SSD of 170 cm was employed. 

Larger children and adolescents (17 pts) was treated in lateral position with 

two opposite fields (AP/PA) and appropriate SSD to cover the whole body. 

Compensator were used to reduce build up regions only in the second group. 

For all patients lungs were shielded by blocks. No compensator were used 

for smaller peripheral regions that were placed near penumbra fields. Dose 

calculation have been performed on pinnacle TPS on TC images for all body. 

In vivo dosimetry during all treatments checked dose delivered. For each patient 

physical and radiobiological evaluation has been performed. Mean target 

S 303 

dose was 12 b 1,5 Gy, (from a minimum of 7,5 b 2 Gy to a maximum of 13,4 b 

1,5 Gy), maximum lung mean dose was 6,5 b 2 Gy. Equivalent uniform dose 

(EUD) was also calculated with TPS on target volume, lung, thyroid, lens and 

gonads. It was quite bigger than mean dose in all patients. A first clinical 

evaluation was performed during treatment and all pts have been followed for 

three months after BMT. 

Results: All pts completed treatment in the prescribed time with prescription 

dose delivered. No patient required strong support therapy during treatment 

nor in the first 3 months after therapy. Mean follow-up is 10 months (range:1- 

24). No major complications were observed. 

Conclusions: The major advantage of this physical approach is increased 

dose information correlating to treatment efficiency. To evaluate relationship 

between EUD and acute/ late toxicity of treatment a statistical analysis is under 

study. Results are too preliminary to allow meaningful evaluation although 

whole engraftment was observed in all patients. 

Clinical/Disease sites : Palliation/Supportive 

care/Patient support 

954 poster 

131-METAIODOBENZYLGUANIDINE (131 MIBG) THERAPY FOR 

PATIENTS WITH MALIGNANT PHEOCHROMOCYTOMA AND PARA- 

GANGLIOMA: THE ISRAELI EXPERIENCE 

M. Shilkrut 1 , R. Bar-Deroma 1 , G. Bar Sela 1 , A. Kuten 1 

1 RAMBAM HEALTH CARE CAMPUS, FACULTY OF MEDICINE, TECHNION, 

Oncology, Haifa, Israel 

Purpose: Malignant pheochromocytoma (PCC) and paraganglioma (PGG) 

are rare diseases with poor prognosis and poor response to chemotherapy/EBRT. 

131-MIBG selectively concentrates in chromaffin tissues, and has 

been used for both scintigraphic localization and systemic treatment of PCC 

and PGG. The following is a report of clinical experience at RHCC - an Israeli 

refferal center for 131- IMBG therapy - in the treatment of malignant PCC and 

PGG by 131-MIBG. 

Materials: The charts of 9 patients (pts) with malignant PCC (n=6) and PGG 

(n=3), treated at RHCC between 2000 and 2007, were reviewed. The majority 

of pts were selected for 131 MIBG therapy based upon positive tracer uptake 

studies. Response to 131-MIBG therapy was evaluated by tumor, hormone 

and symptomatic relief criteria. 

Results: Age ranged between 21 - 67 yrs (median: 47 yrs); 6 (67%) were 

men, 3 (33%) were women. One pt with PCC had neurofibromatosis type 

1. The most common site of metastases were the lungs (6 pts, 67%); 5 pts 

(56%) had bone metastases. 8/9 pts (89%) were symptomatic. 2 pts were 

treated by EBRT prior to or in between 131-MIBG treatments. Number of 131 

MIBG treatments ranged from 1 to 4 with a mean of 2.2±1.1. 3 pts (33%) 

received one treatment; 2 pts (23%) received 2 treatments, 3 pts (33%) received 

3 treatments, and one pt (11%) received 4 treatments of 131-MIBG. 

The median initial dose was 5.3 GBq (144 mCi) (range: 3.7 GBq - 5.6 GBq; 

100-150 mCi). The second, third and forth treatments were 5.6 GBq each 

(150 mCi). The median cumulative dose was 98.1 GBq (2650 mCi) (range: 

5.6 GBq 22.4 GBq; 150 600 mCi). All pts received potassium iodide prior 

to 131 MIBG. The median follow up is 25 months (range: 7-50 months). 8/9 

pts are alive. There were no complete responses. 4 pts (44%) had partial 

objective tumor response, 2 pts (23%) had stable disease and 3 pts (33%) 

progressed after therapy. 5 pts (56%) experienced symptomatic response. 

Hormone response rate was 56%. One pt (11%) had transient thrombocytopenia 

grade 1, one pt (11%) developed subclinical hypothyroidism. 

Conclusions: Tumor and hormonal response as well as symptomatic relief 

can be achieved by 131-MIBG therapy, with minor side effects. 131 MIBG is 

a potent palliative adjunct in pts with malignant PCC and PGG. 

955 poster 

A UK INSITITUTION S 10 YEAR EXPERIENCE OF TREATING 

INTRACRANIAL METASTATIC DISEASE FROM MELANOMA 

S. Gwynne 1 , N. Howes 1 , J. Barber 1 , T. Abbas 2 

1 VELINDRE CANCER CENTRE, Clinical Oncology, Cardiff, United Kingdom 

2 VELINDRE CANCER CENTRE, Medical Oncology, Cardiff, United Kingdom 

Purpose: The CNS is a known site of metastases from malignant melanoma 

with incidence ranging from 10-40% in clinical studies, with an even higher 

incidence in autopsy series. In the absence of effective systemic therapies, 

WBRT has been the standard of care for such patients, either as adjuvant 

treatment after surgery or stereotactic RT, or as the only treatment modality 

in patients with multiple lesions. The doses and fractionation schemes vary, 

in keeping with the uncertainties around the optimal regime for the treatment

S 304 CLINICAL/DISEASE SITES : PALLIATION/SUPPORTIVE CARE/PATIENT SUPPORT 

of melanoma.. There is some evidence that doses greater than 30Gy are 

associated with an increased response in melanoma. Several groups have 

audited their survival following WBRT in the treatment of this condition but 

there is a paucity of UK studies. The overall median survival of patients with 

CNS metastases treated with WBRT ranges between 9 and 20 weeks with 1 

yr survival rates of less than 13%. We audited our practice to assess whether 

our survival data was comparable to the published literature. 

Materials: All patients referred to Velindre Hospital with a diagnosis of 

melanoma between 1997 and 2007 were retrieved from an electronic 

database. 270 of these received radiotherapy and 117 of these were identified 

as having WBRT. Data regarding demographics, treatment and survival 

for this group were compiled. 

Results: 66 males and 51 females were included with a mean age at the 

start of treatment of 55.7 yrs (18.37 - 81.47). Median time to development of 

brain mets from diagnosis was 13.32 months Median survival for all 117 pts 

was 9.71 weeks. (0.28691.14) with a 1 yr survival of 4.3% 41.035% (48/117) 

of melanomas were located on the trunk and were associated with a slightly 

better median survival of 10.29 weeks compared to 8.71 weeks in the 41.03% 

(48/117) who had limb primaries. Median survival of those who had surgery 

followed by WBRT (10/117) was 12.07 weeks. Median survival according 

to dose was 14.29 weeks with dose >30Gy, 13.21 wks with dose equal to 

30Gy, and 8 weeks with dose < 30Gy (p

959 poster 


C-TELOPEPTIDES: FROM BONE RESORPTION MARKER TO 

TUMOR RESPONSE PREDICTOR 

M. C. Lopez Carrizosa 1 , P. M. Samper Ots 1 , A. Rodriguez Perez 1 , J. M. 

Delgado Perez 1 

1 HOSPITAL CENTRAL DE LA DEFENSA GOMEZ ULLA, Oncology- 

Radiotherapy, Madrid, Spain 

Purpose: To assess the levels of C-telopeptides (CTX) in serum patients 

with bone metastases (BM) treated with zoledronic acid (ZA) and to evaluate 

the usefulness of this marker of bone resorption to predict the bone disease 

progression, the response to ZA therapy and its effect on prognosis. 

Materials: A retrospective ansis was performed between march/03 and 

dec/06. 26 patients with BM and ZA treatment were included. Median 

age was 69 years (range, 52-84) and 17 male patients (65.4%). 49% of 

patients (13) with prostate carcinoma, 31% (8) with breast cancer patients 

and 20% (5 patients) with other solid tumors. 42,3% were G3. Serum tests 

such as peripheral blood test and CTX (β-crossLaps), urinary phosphocalcic 

metabolism and bone gammagraphy were performed at baseline, 6, 12, 18 

and 24 months. Intravenous ZA, 4 mg every 3-4 weeks and a daily intake 

of oral calcium plus vitamine D were administered until the development of 

skeletal complications (SC) or the study completion. Statistical analysis was 

performed using the SPSS v.12.0 program. 

Results: At the time of diagnosis, 57,7% of patients had multiple BM and 

42,3% received palliative irradiation. In the course of the study, there were 

SC in 16.7% of patients who all received antalgic radiotherapy. At the end 

of the study, 68% of patients had disease progresi 32% who had not. No 

severe side effects have been related. At baseline, the CTX median value 

was 562,475+305,179 pg/ml (69,131330 pg/ml) and alkaline phosphatase 

(AP) :123,153+90,195 U/L (53-513 U/L) and no differences statistically significant 

were found out between prostate cancer and breast cancer patients. 

During the study, the AP levels, the urinary phosphocalcic removal and the 

calcium serum levels were not statistically significant. At 6 and at 12 months 

after starting the ZA treatment, CTX levels decreased, being statistically significant 

(p= 0.0001 and p=0.030, respectively). Even though prostate cancer 

patients had lower baseline CTX level than breast cancer patients, there 

was not a significant correlation. On the contrary, the CTX level at 6 months 

was significantly reduced in prostate cancer vs breast cancer patients (p= 

0.0001). Patients without disease progression after completion of the study 

had a baseline CTX level (p=0.04), at 18 months (p=0.006) significantly lower 

than patients with bone disease progression. 5 or more BM were related with 

a lesser tumor control (p=0.017), a lower decreased CTX levels, a worse outcome 

and an increased CTX levels at 18 months (p=0.006) compared with 

less than 5 BM. Patients with SC had an increased CTX levels, statistically 

significant at 12 and at 18 months (p=0.008 and p=0.006, respectively). 

Conclusions: Decreased CTX levels predict the response to ZA therapy, a 

lower incidence of SC and a higher probability of tumor control. 

960 poster 

CHALLENGES AND ISSUES IN CONDUCTING CLINICAL TRIALS IN 

PALLIATIVE RADIOTHERAPY 

M. McGarry 1 , A. Clayton-Lea 2 , C. Small 3 , O. McArdle 3 , P. Thirion 3 , M. 

Moriarty 3 

1 

ST. LUKE’S HOSPITAL, Clinical Trials Unit, Dublin, Ireland Republic of 

2 


of 

3 


Republic of 

S 305 

Purpose: Malignant spinal cord compression (MSCC) represents one of the 

major cancer-related neurological complications, involving both a vital and 

functional prognosis. Radiotherapy (RT) has a major role, as sole modality 

or in combination with decompressive surgery. To better define the optimal 

radiotherapy modalities, two ICORG palliative clinical trials were initiated and 

are presently conducted in our institution. 

Materials: The ICORG 05-03 is an ongoing prospective randomised clinical 

trial comparing 10 Gy/1 fraction vs. 20 Gy/5 daily fractions in patients 

(pts) with MSCC treated with RT alone. The ICORG 07-11 is an ongoing 

phase II trial assessing the efficacy and toxicity of a radiobiological-based 

re-irradiation in pts with MSCC arising in a previously irradiated area. The 

2 trials are locally co-ordinated by 1 clinical research radiation therapist. Pt 

evaluation and follow-up (FU) are the same in both trials and involves recording 

history, previous treatment, symptoms (pain and motricity) and QoL questionnaire 

before RT and at weeks 1, 5, 12 and every 3 mths either by direct 

clinical evaluation or phone call. 

Results: The ICORG 05-03 is opened since January 2006 and ICORG 07- 

11 since October 2007. To date, 37 pts and 2 pts are included in the above 

trials out of a total of 217 and 17 pts screened respectively, representing an 

overall uptake rate of 17% (17% in ICORG 05-03; 12% in ICORG 07-11). All 

patients were treated during the emergency on-call period (100% after 17.00) 

and were mostly referred to us at the end of the week (48% Thursday/Friday). 

The median duration of screening, recruitment and initial assessment was 

70 minutes (range 40 to 100 mins) with the co-ordinator using sensitivity and 

tact when approaching potentially eligible palliative patients. The reasons 

for non-inclusion were: ineligibility (78% n=152), missing information (15% 

n=29), clinician refusal (4% n=8) and patient refusal (3% n=6). Refusal of 

eligible patients to participate was very low (11% of all eligible pts) indicating 

a strong willingness among palliative patients to be involved in clinical 

trials. Generous time is given for FU assessment with sensitivity essential 

(co-ordinator is frequently informed of a patient’s RIP by a relative at FU) 

having one co-ordinator recruit and FU patients is deemed essential as this 

cohort of patients regularly voice appreciation for the continuity of contact. 

Conclusions: Conducting and co-ordinating clinical trials in palliative radiotherapy 

represents a specific challenge because of the specific psychological 

and clinical context, in addition to the work environment (after hours, end 

of week). Research involving palliative patients is challenging but essential 

in order to optimise treatment for future patients. In our experience this is 

of paramount importance to patients participating in these two trials and is 

regularly expressed by them as a source of satisfaction and comfort. This 

research is supported by the St Luke’s Institute of Cancer Research. 

961 poster 

CONTROLLED-RELEASE OXYCODONE (OXYCONTIN) TABLETS 

FOR THE TREATMENT OF CANCER PAIN AND RADIOTHERAPY IN 

NAIVE PATIENTS: PRELIMINARY RESULTS. 

F. Piro 1 , L. Ziccarelli 1 , P. Ziccarelli 1 , R. Siciliano 1 , P. Indrieri 1 , E. Cervo 1 

1 OSPEDALE MARIANO SANTO, Cosenza, Italy 

Purpose: In patients with bone metastasis or primitive cancer the pain grade 

moderate-severe is often complicated by neuropathic component so that it is 

impossible to deliver an efficacy analgesic therapy without a large knowledgeable 

of palliative care and symptom management. To evaluate the efficacy of 

controlled-release oxycodone (OxyContin) tablets in patients with pain submitted 

to radiotherapy. 

Materials: From January 2007 to december 2007, 35 patients, avarage age 

55 aa, with cancer pain grade severe-moderate and without an efficacy analgesic 

therapy, were enrolled. So before treatment planning and irradiation 

procedures they were administered 40 mg/die of controlled- release oxycodone 

tablets. 

Results: Every patient completed the analgesic therapy prescribed, in out patient 

setting, without a dose variation or breakthrough pain episodes. During 

treatment simulation and all treatment delivery the patients maintained the 

set-up position established by radiation oncologist. Among all the enrolled 

patients, 32 were affected with bone metastasis, the other 3 were primitive 

cancers. The pain control was effective in 31 patients and occurred immediately 

after the first administration drug of 40 mg/die; for the other 4 patients 

pain control was obtained with 80 mg/die. The analgesic therapy was performed 

for 3-4 months without significant adverse effects and without use of 

others analgesic drug. 

Conclusions: The controlled-release oxycodone tablet is a good drug, without 

the ceiling effect of the equivalent complexed drug. It is efficacy both in 

association or not with radiotherapy, according to WHO three-step analgesic 

ladder. Pain management is an ongoing process, opioid analgesics such as 

radiotherapy treatment are very important for moderate-severe pain in cancer 

patients. 

962 poster 

DECISION SUPPORT IN RECTAL CANCER: ADAPTIVE CONJOINT 

ANALYSIS AS A MEASURE OF INDIVIDUAL TREATMENT PREFER-


ENCE 

A. Pieterse 1 , C. Marijnen 2 , M. Baas-Thijssen 1 , C. van de Velde 3 , A. 

Stiggelbout 1 

1 

LEIDEN UNIVERSITY MEDICAL CENTER, Medical Decision Making, Leiden, 

Netherlands 

2 

NETHERLANDS CANCER INSTITUTE, Radiation Oncology, Amsterdam, 

Netherlands 

3 

LEIDEN UNIVERSITY MEDICAL CENTER, Surgery, Leiden, Netherlands 

Purpose: Patient participation in treatment decision making is increasingly 

advocated. A commonly used direct elicitation technique to evaluate patients’ 

preferences is the Treatment Tradeoff Method (TTM), in which the patient is 

presented with descriptive and probabilistic information on reasonable treatment 

alternatives. However, this technique has been shown to be prone to 

biases. Adaptive Conjoint Analysis (ACA) is an individually-tailored computerized 

indirect preference elicitation method. It presents the patient with pairwise 

comparisons of (positive and negative) treatment outcomes, which are 

increasingly tailored to what the patient considers relevant tradeoffs. So far, 

ACA has not been tested in cancer patients. In the treatment of rectal cancer, 

preoperative radiotherapy has shown to improve local control, but not overall 

survival in several randomised studies. Preoperative radiotherapy is known to 

increase probability of faecal incontinence and sexual dysfunction. We therefore 

evaluated the feasibility of ACA for assessing treatment preferences in 

rectal cancer patients. 

Materials: Sixty-eight disease free rectal cancer patients previously treated 

in the TME trial, were asked to complete a TTM- and an ACA-task. For the 

probabilities of outcome, figures were derived from the TME trial. TTM- and 

ACA-based treatment preferences were compared. In addition, relative importances 

of survival, local control, fecal incontinence, and sexual dysfunction 

were assessed using ACA. 

Results: All patients completed the TTM- and 66 participants completed the 

ACA-task. However, about half of the patients indicated to find the ACA difficult 

to complete. Comparing ACA- and TTM-based treatment preferences, 

only 20/65 respondents were congruent. ACA-based treatment preferences 

were unrelated to previous treatment, whereas TTM-based preferences were 

strongly related to previous treatment. In the ACA-task, local control and faecal 

incontinence were considered more important than survival and sexual 

dysfunction with the given range of probabilities. 

Conclusions: ACA utilities per se should not be used to base individual clinical 

decisions on, but seems a promising tool in helping patients to reflect on 

tradeoffs underlying decisions. In comparison with the TTM, ACA is more 

likely to exclude biased treatment preferences. 

963 poster 

EFFECTS OF ERYTHROPOETIN BETA ON HEMOGLOBIN LEVEL 

AND QUALITY OF LIFE IN ANEMIC CANCER PATIENTS RECEIV- 

ING RADIOTHERAPY +/- CHEMOTHERAPY. A MULTICENTER, 


H. Athanassiou 1 , J. Skarlatos 1 , D. Antonadou 1 , K. Panousaki 1 , N. 

Coliarakis 1 , C. Zabatis 1 , K. Beroukas 1 , P. Karageorgis 1 

1 HELLENIC GROUP FOR CLINICAL RADIATION ONCOLOGY, Athens, Greece 

Purpose: The current prospective, multicenter study was performed to evaluate 

the effectiveness, safety and quality of life benefit of recombinant human 

erythropoietin beta (EPO beta) in anemic cancer patients undergoing a 5-7 

week course of radiation therapy +/- chemotherapy. 

Materials: Between January 2004 and June 2006, a total of 123 cancer patients 

with anemia (Hb 9-12 g/dL) were enrolled in this 16- week study, 119 

were eligible for efficacy evaluation. Patients initially received EPO beta at a 

dose of 20,000 units (U) SC three times per week. If Hb increased by >/= 2 

g/dL after two weeks, the EPO dose was decreased by 50%. If the Hb was > 

14 g/dL at any time during the study, EPO beta was discontinued. Endpoints 

were changes in Hb levels and quality of life (QOL) parameters by using the 

linear analog scale assessment (LASA) instrument. 

Results: Mean Hb at baseline was 10.5±1.0 g/dL. There was a significant 

increase in the mean Hb levels from the first week of radiotherapy with the 

peak value at week 7 from the baseline (31.2%). The mean increase in Hb 

from baseline to the time of final evaluation was 2.04 +/- 1.23 g/dL (P < 0.05). 

Blood transfusion was necessary in 4 patients. EPO beta therapy was found 

to be well tolerated. Significant improvement of mean Linear Analog Scale 

Assessment (LASA) scores for energy level, ability to perform daily activities, 

and overall QOL from baseline to the time of final evaluation was also 

observed. 

Conclusions: Treatment with erythropoietin beta was safe and effective in 

cancer patients undergoing radiotherapy +/- chemotherapy. Hb levels were 

significantly increased during the radiotherapy period and quality of life was 

significantly improved. 

964 poster 

FIRST RESULTS OF THE PROSPECTIVE HOSPITAL DEL MAR 

BONE HEALTH PROSTATE CANCER STUDY (HMBHPC) IN MEN 

RECEIVING SHORT TERM HORMONOTHERAPY AND PELVIC 

RADIOTHERAPY 

J. Lozano Galan 1 , X. Nogués 2 , P. Foro 1 , X. Sanz 1 , P. Dengra 1 , V. Piera 

1 1 1 1 1 2 

, I. Membrive , N. Rodríguez , A. Reig , J. L. López , M. J. Peña , M. 

Algara 3 

1 

IMAS-HOSPITAL DE LA ESPERANÇA, Radiation Oncology, Barcelona, 

Spain 

2 

IMIM-HOSPITAL DEL MAR, URFOA-IMIM. Universitat Autònoma de 

Barcelona, Barcelona, Spain 

3 

IMAS-HOSPITAL DE LA ESPERANÇA, Radiation Oncology. Universitat 

Pompeu Fabra, Barcelona, Spain 

Purpose: Long-term androgen deprivation therapy produces alterations in 

bone mass density (BMD) and bone turnover markers, increasing fracture 

risk. Low levels of 25-OH vitamin D (VitD) promotes bone resorption due to 

an increase of PTH . The HMBHPC study is an ongoing phase IV study addressed 

to evaluate the effect of short-term (6 months) androgen deprivation 

therapy (STADT) and radiotherapy (RT) on bone health in our prostate cancer 

patients. The aim of the present analysis is to assess bone health baseline 

status in this cohort. 

Materials: Patients with localised prostate cancer before start STADT and RT 

were included. BMD and VitD level, were measured at baseline. A validated 

calcium intake questionnaire was also filled. 

Results: Twenty-four patients have been included so far. Age ranged from 

58 to 80 with a mean (+/- SD) of 71.8 years (+/- 6.12). Baseline BMD values 

(WHO criteria) were:12.5% normal, 54.2% had osteopenia and 33.3% had 

osteoporosis. Ninety percent had baseline values of vitD below 30 ng/ml. 

Total calcium intake of patients was 1500 mg/day . 

Conclusions: Our preliminary results strongly suggests that we should routinely 

evaluate at baseline VitD status before starting STADT and radiotherapy 

in prostate cancer patients, because hypovitaminosisD (


completion rates were to low to provide meaningful comparisons between the 

two radiotherapy regimens. The median OS was 9 months. The OS was 64% 

(+/- 5%) after 6 months, 28% (+/- 4,5%) after 12 months. The six-months 

and one-year EFS was 28.4% (+/- 4.8%) and 1.2% (+/- 1.2%), respectively. 

The OS at 6 and 12 months for arm A and arm B were 65 vs 65% and 29 vs 

26%, respectively. The EFS at 6 and 12 months were 30 vs 26% and 2 vs 

0%, respectively. There was not a statistically significant difference in terms 

of OS and EFS between the two radiotherapy regimens (p= 0.423 and 0.735, 

respectively). Median OS was 8 and 10 months in arm A and B, respectively. 

Nor the class (V-VI) by the Curran RPA neither the Ki-67 expression and the 

p53 status have resulted as prognostic factors. 

Conclusions: The two radiotherapy regimens seem to be feasible and 

enough effective as palliative treatment for "poor prognosis" GBM patients 

but no difference in terms of OS and EFS has been found. The study is on 

going in order to reach the number of patients established by the statistical 

analysis. As reported in the literature, we can confirm the difficulty of performing 

the neurological and QOL evaluation in a group of patients with poor 

clinical condition and fast pathological progression. 

966 poster 

INTERNATIONAL PATTERNS OF PRACTICE IN PALLIATIVE RADIO- 

THERAPY FOR PAINFUL BONE METASTASES 

A. Fairchild 1 , T. Barnes 2 , S. Ghosh 3 , E. Ben-Josef 4 , D. Roos 5 , W. 

Hartsell 6 , T. Holt 7 , J. Wu 8 , N. Janjan 9 , E. Chow 2 

1 

CROSS CANCER INSTITUTE, Radiation Oncology, Edmonton, Canada 

2 

ODETTE CANCER CENTRE, SUNNYBROOK HEALTH SCIENCES CENTRE, 

Radiation Oncology, Toronto, Ontario, Canada 

3 

CROSS CANCER INSTITUTE, Experimental Oncology , Edmonton, Canada 

4 


5 

ROYAL ADELAIDE HOSPITAL, Radiation Oncology, Adelaide, Australia 

6 

GOOD SAMARITAN CANCER CENTER, Radiation Oncology, Downers 

Grove, Illinois, USA 

7 

MATER CENTRE, Radiation Oncology, South Brisbane, Australia 

8 

TOM BAKER CANCER CENTRE, Radiation Oncology, Calgary, Canada 

9 

UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER, Radiation 

Oncology, Houston, Texas , USA 

Purpose: To determine patterns of practice in palliative radiation therapy 

(RT) for painful bone metastases (BM) in view of randomized controlled trials 

(RCTs) and meta-analyses demonstrating the equivalence of single fraction 

(SF) and multi-fraction schedules. 

Materials: Radiation Oncologist (RO) members of the American Society 

of Therapeutic Radiology and Oncology (ASTRO), the Canadian Association 

of Radiation Oncology (CARO), and fellows of the Royal Australian and 

New Zealand College of Radiology (FRANZCR) currently practicing worldwide 

were invited to participate. Five case scenarios were presented (Table); 

respondents were asked whether they would recommend RT, and if so, 

what dose. Descriptive statistics were compiled as proportions and medians 

(ranges), and two-sided Fisher’s exact test was performed. Forward conditional 

logistic regression was used to identify predictors of use of 8 Gray in 

one fraction (8Gy/1) by ROs currently practicing in Europe. Due to small 

numbers, this could not be performed for UK respondents. 

Results: 962 eligible responses from 47 countries were received from respondents 

in private (21.5%), public (35.0%), community (35.2%) or university 

(36.9%) practice a median of 14 years (1-49 yrs). Overall, palliative RT 

comprised 30Gy. 8.3-58.3% of UK ROs would 

prescribe SF; no UK oncologist would offer doses >30Gy for any case. Significantly 

more European respondents recommended 8Gy/1 for patients being 

retreated (on average 50.0%) compared to initial BM presentation (case 

1)(22/112; 19.6%)(p


968 poster 

MANAGEMENT OF SYMPTOMATIC BONE METASTASES FROM 

BREAST CANCER WITH EXTERNAL RADIOTHERAPY AND IBAN- 

DRONATE: RESULTS OF A PROSPECTIVE, PILOT STUDY. 

V. Vassiliou 1 , K. Christine 2 , L. Michael 3 , T. Athanassios 4 , G. Efstathia 5 , 

P. Theodoros 2 , K. Dimitrios 1 

1 

UNIVERISTY OF PATRAS MEDICAL SCHOOL, Radiation Oncology, Patras, 

Greece 

2 

UNIVERISTY OF PATRAS MEDICAL SCHOOL, Radiology, Patras, Greece 

3 

UNIVERISTY OF PATRAS MEDICAL SCHOOL, Public Health, Patras, Greece 

4 

UNIVERISTY OF PATRAS MEDICAL SCHOOL, Department of Histopathology, 

Patras, Greece 

5 

UNIVERISTY OF PATRAS MEDICAL SCHOOL, Laboratory Clinical Oncology, 


Purpose: We herein report the results of a prospective pilot study that investigated 

the effectiveness of the combination of radiotherapy and ibandronate, 

in women with metastatic bone disease from breast cancer. 

Materials: Patients (n=32) were treated with concomitant application of radiotherapy 

(30-40 Gy) and intravenous monthly infusions of ibandronate (6 

mg, 10 monthly cycles) and underwent clinical and radiological assessments 

prior to therapy and at the time points of 3, 6 and 10 months post the onset of 

the combined treatment. The clinical status of each patient was assessed by 

using a bone pain scale graded from 0 to 10 (10 = worst possible pain, 0 = no 

pain), performance status evaluation (Karnofsky performance status index, 0- 

100), and a quality of life questionnaire (EORTC-QOL-physical functioning). 

The analgesic consumption was also recorded at all evaluation time points in 

detail and opioid requirement was transformed into daily oral morphine equivalents 

(mg). Bone lesions were assessed with computed tomography (CT) by 

using a bone algorithm and slices of 3 mm thickness. The bone density of 

each metastatic bone lesion was measured in Hounsfield units (HU) on representative 

CT images and all delineated images were kept for comparison 

at successive evaluations. Pain responses at a specific time point were evaluated 

by comparing pain scores to those of the preceding assessment. A 

complete pain response was defined as a pain score of zero with no concomitant 

increase in opioid use (stable or reduced opioid need). 

Results: Mean bone pain score decreased from 5.1 at baseline to 0.8 at 3 

months, with further reductions at later time points (all p

1 


1 

HOSPITAL, Radiation Oncology, Taormina, Italy 

2 


3 

HOSPICE, Medical Oncology, Perugia, Italy 

4 


Rome, Italy 

5 

FATEBENEFRATELLI - HOSPITAL, Radiation Oncology, Rome, Italy 

6 

HOSPITAL, Radiation Oncology, Cosenza, Italy 

Purpose: To determine the incidence of RID. 

Materials: Fifty-five Italian radiation oncology Centres took part in this trial 

and 1020 pts were enrolled. The accrual lasted 3 consecutive weeks. Evaluation 

was based on diary cards filled in daily by pts during radiotherapy (RT) 

and 1 week after stopping it. Diary cards recorded both the onset and intensity 

of diarrhea. Prophylactic and symptomatic drug prescriptions were also 

registered. 

Results: 1004 pts were eligible for this analysis. There were 343 (34%) pts 

submitted to irradiation on pelvis (291) or upper abdomen (52). Chemotherapy 

was administered previously or concomitantly to RT in 392 (39%) and 

120 (12%) pts, respectively. 147 of 1004 (15%) pts had diarrhea; the median 

time of diarrhea was 5 days (range, 1-51): the median minimum number 

of daily events was 1 (range, 1-7) with a median maximum events of 3 

(range, 1-23). 82 of 147 pts (56%) had a drug prescription for preventing 

diarrhea. The symptom was mainly observed among pts treated with pelvicabdominal 

fields; diarrhea was reported also in 19% of pts treated for head 

and neck cancer, 12% of pts with brain tumors, 7% of pts with thoracic malignancies, 

4% of pts with breast cancer, and 8% of pts with skin/extremities 

tumors. In the evaluation of the onset of diarrhea, we found the following factors 

to be statistically significant predictors of increased likelihood of diarrhea: 

gender (male vs female; p

S 310 CLINICAL/DISEASE SITES : PROSTATE 

Conclusions: The present study showed a significant impact of symptoms 

after RT on patients’ QoL and a significant association between patients’ anxiety 

and their QoL. The severity of symptoms following the RT correlated with 

a compromised QoL and levels of anxiety. Symptom complications following 

radiotherapy treatment were significantly associated with a poor quality of life 

and high levels of anxiety. They result in fatigue, sleeplessness, pain, and 

diarrhoea all affecting their well-being. The worsening in patients’ QoL perception 

did not lead to a significant reduction in daily activities or treatment 

tolerance. 

974 poster 

THE LEKSELL GAMMA KNIFE IN TREATMENT OF LARGER VOL- 

UMES BRAIN METASTASES 

G. Simonova 1 

1 HOSPITAL NA HOMOLCE PRAGUE 5, Department of Stereotactic and 

radiation neurosurgery, Prague, Czech Republic 

Purpose: Aim of study was to analyze treatment results of patients with brain 

metastases 15 000 mm3 and larger 

Materials: Material, method: 117 patients (pts) with 121 brain metastases of 

volume 15 000 mm3 and larger were treated over a period of 10 years. Characteristics: 

median of age was 59 years, 62% pts. with solitary metastasis 

and 38 % with 2-4. Histology: non small lung cancer 33 %, breast cancer 

9,5%, melanoma 10%, GIT cancer 11%, others 21,5%. Median of Karnofsky 

rate (KPS) was 80, median of gross tumor volume (GTV) was 18 750 

mm3 (15 100-37 300 mm3), planning treated volume (PTV) was 22 700mm3 

(16 000 41 500 mm3), median of of minimal dose (D min) was 18 Gy (14-20 

Gy). All patients underwent radiosurgery using Leksell gamma knife and were 

controlled every 4 months. Following categories were used to evaluate local 

effect of treatment: complete regression (CR), partial regression (PR), stabilization 

(ST) (no change), progression (PROG) and local reoccurrence (REC). 

Toxicity was measured by RTOG/EORTC SOMA LENT system. Progression 

free survival (PFS) was measured from the day of treatment. Different potential 

prognostic factors were proposed for statistical analysis: sex, age, KPS, 

histology, status of primary tumor, other organ dissemination, GTV, D min. 

Following events were studied: PFS and tumor response. The univariate 

analyses was performed using log-rank test. The multivariate analyses were 

performed with Cox proportional hazards model using the forward stepwise 

(conditional likelihood ratio) method. Variables with significant p value (p0.05) 

at least in one of two actuarial analyses were considered as possible prognostic 

factor for relevant event. 

Results: Complete regression was achieved in 2.5%, PR in 55%, ST in 

25.5% and PROG was found in 17%. REC was observed in 8 % .The acute 

toxicity grade 2,3 in 10% of patients and late toxicity grade 2,3 were observed 

in 12%. Statistically significant factors for local tumor control were 

sex (p=0.006 log rank, p=0.032 Cox) (better results for male) and histology 

(p=0.003 log rank) (better results for renal cell carcinoma, breast carcinoma 

and melanomas). Statistically significant factors PFS were histology (p=0.002 

log rank) (the better results for melanoma and renal cell carcinoma) and 

metastatic extent outside brain (p=0.035 log rank, p=0.017 Cox) (the worse 

results for other organ dissemination). The median of PFS was 7 months (1- 

90 months). Statistically significant factors for PFS possessed to identify the 

favorable subgroup of treated patients with following characteristics: patients 

with breast or renal cell carcinoma and without other organ dissemination. 

Conclusions: Despite the 17% incidence of local progression method remains 

the important treatment modality for larger volume metastases. 

975 poster 

THE USE OF A FINITE ELEMENT MODEL IMPROVES THE PREDIC- 

TION OF FEMORAL FRACTURE RISK IN COMPARISON TO THE 

PREDICTION OF EXPERIENCED CLINICIANS. 

Y. van der Linden 1 , J. van Aken 2 , N. Verdonschot 2 , H. Huizenga 3 , E. 

Tanck 2 

1 

RADIOTHERAPEUTIC INSTITUTE FRIESLAND, Leeuwarden, Netherlands 

2 

UNIVERSITY MEDICAL CENTRE NIJMEGEN, Orthopaedic Research Lab, 


3 

UNIVERSITY MEDICAL CENTRE NIJMEGEN, Dept. of Radiotherapy, 


Purpose: Bone metastases occur in about 15% of all cancer patients. Pathological 

fractures that may develop in these lesions are most frequently located 

in the femur. Unfortunately, it is extremely difficult to determine the risk of 

fracture, even for experienced clinicians. As a result, patients are surgically 

overtreated, whereas some patients, who are defined to be at low risk, may 

fracture their bones [1]. The purpose of this study was to develop a femur 

(patient) specific finite element model to improve the prediction of fracture 

risk under stance loading. In addition, we tested if our model was better in 

predicting fracture risk than experienced clinicians. 

Materials: Eight human cadaver femora with and without simulated metastases 

were CT-scanned (Philips, ACQsim, 120kV, 220mAs, 3mm slices). A 

solid calibration phantom (Image Analysis, 0, 50, 100 and 200 mg/ml cal- 

cium hydroxyapatite) was included in each scan. From the scans, eight finite 

element (FE) models were generated using brick elements with sizes of 

about 1x1x3 mm. The ash density of each element was computed from the 

calibrated CT scan data. Using ash densities, non-linear isotropic mechanical 

properties were implemented [2]. After scanning, laboratory experiments 

were performed. The femora were loaded under compression until fracture. 

During the experiments, the failure forces and the course of failure were registered. 

These experiments were simulated in the FE-models, in which plastic 

deformation simulated fracture of the bones. The relationship between the 

experimental failure force and predicted failure force was determined using 

Pearson’s correlation. Five experienced clinicians (3 orthopaedic surgeons, 1 

radiologist, 1 radiation oncologist) were asked to rank the femora on strength 

using X-rays (AP and ML) and additional information on gender and age. The 

Spearman’s rank correlation coefficients were calculated between prediction 

and experiment for both the FE-model and the expert rankings to compare 

the performance of the clinicians. 

Results: A strong correlation (r2 = 0.93) was found between the experimental 

failure force and predicted failure force. The course of failure, visible by 

the plastic deformation, showed similarities with the fracture locations found 

in the experiments (figure 1). The Spearman’s rank correlations between 

experiment and predictions ranged between r2=0.23 and r2=0.54 for the clinicians, 

whereas it was significantly higher, r2=0.86, for the FE-model (figure 

2). 

Conclusions: In femoral metastases, the prediction of fracture risk has been 

mainly based on X-rays. We showed that femur specific FE models better 

predicted fracture risk than experienced clinicians. The model is now under 

further development in order to clinically implement it for prediction of in vivo 

fracture risks in cancer patients suffering bone metastases. References 1. 

Van der Linden et al, JBJS, 86B:566-573, 2004. 2. Keyak et al, Clin Orthop 

Rel Res, 437:219-28, 2005. 

Clinical/Disease sites : Prostate 

976 poster 

7-YEAR PSA RELAPSE-FREE SURVIVAL AFTER I-125 PROSTATE 

BRACHYTHERAPY 

R. Laing 1 , S. Khaksar 1 , S. Langley 1 , I. Wells 1 , J. Nobes 1 

1 THE ROYAL SURREY COUNTY HOSPITAL, St. Luke’s Cancer Centre, 

Guildford, United Kingdom 

Purpose: Over 1300 patients have undergone I-125 prostate brachytherapy 

(BXT) in our unit. We present outcome data for the first 500 consecutive 

patients. 

Materials: A prospective database of patients treated with BXT between 

1999-2004 was analysed. Patients were stratified into low (51%), intermediate 

(36%) and high (13%) risk, as defined by the MSKCC Prognostic Index. 

Patients received 145Gy BXT alone (47%), BXT with neoadjuvant androgen 

deprivation (35%), 45Gy external beam radiotherapy with 110Gy BXT (3%), 

or trimodality therapy. Biochemical relapse-free survival (bRFS) and PSA 

nadirs were analysed for treatment received in each risk group. 

Results: Median follow-up was 61 months (range 38-105) with a mean patient 

age of 63 years. Prostate cancer-specific survival was 99.6%. 37 patients 

(7.4%) experienced biochemical failure according to the 2006 RTOG- 

ASTRO Phoenix Consensus definition (PSA ≥ nadir plus 2 ng/ml): 6% low, 

9% intermediate, and 11% high risk patients. Actuarial 7-year biochemical 

relapse-free survival (bRFS) was 94% for low risk, 90% for intermediate risk, 

87% for high risk, and 91% for all patients. PSA nadir ≤ 0.5 ng/ml was 

achieved by 84% at both 4 (n=268) and 5 years (n=160); 5-year PSA ≤ 0.2 

ng/ml was 73%. Mean D90 was 147Gy for BXT alone (n=379), and 112Gy 

for boost patients (n=81). 

Conclusions: This updates our previously reported bRFS following prostate 

BXT, confirming that results of this treatment, both alone and as combination 

therapy, are durable beyond 5 years.

977 poster 

A VIRTUAL FLUOROSCOPY SYSTEM TO AID IN PROSTATE SEED 

IMPLANTS 

V. Sarkar 1 , A. Gutierrez 1 , S. Stathakis 1 , G. Swanson 1 , N. Papanikolaou 1 

1 UTHSCSA, Radiation Oncology, San Antonio, USA 

Purpose: To develop a software platform to produce a virtual fluoroscopic 

image of permanent brachytherapy seeds placed in the prostate. 

Materials: Any real-time, intra-operative treatment planning system (TPS) 

allows users to perform a sonographic prostate volume study in the operating 

room and use the information to generate a seed implant plan. With the 

plan created, the spatial coordinates of each seed can be extracted from 

the treatment planning system. In this case, we obtained the data from 

Nucletron’s SPOT TM system (Veenendaal, The Netherlands). This information 

was used as input to an in-house-developed software platform based on 

Matlab R○(Version 8.0, Natick, MA). The software utilizes the optimized seed 

location from the pre-plan and performs a forward projection implementing 

a divergent x-ray beam model to determine a virtual fluoroscopic image of 

the planned seeds. The primary forward projection is performed using an 

arbitrary coordinate system. Since there is no exact fixed placement of the 

fluoroscopy system over the patient, the center of the image must be input 

by the user so that the system reprojects the seeds. The user also has the 

option of varying the source-to-object distance as well as perform some small 

translational and rotational adjustments to make the final calculated distribution 

agree with the actual geometry of the fluoroscopic system relative to the 

patient. To obtain orientation information, the projected seeds can be overlaid 

on a radiograph of the patient taken prior to the start of the implant procedure. 

Results: Preliminary testing shows that the system works as expected for 

projections created at any angle. 

Conclusions: This system allows for quick (on average less than 5 seconds 

on an off-the-shelf PC with a 2 GHz dual core processor) generation of a virtual 

fluoroscopic image of the planned seed pattern. The image can be used 

as a verification tool to aid the physician in evaluating the implant throughout 

the procedure and take remedial action should the implant deviate from the 

planned distribution. Moreover, multiple virtual images can be compared to 

actual post-implant, fluoroscopic images to detect seed placement deviations 

and opens the eventual possibility of calculate ensuing dosimetric differences. 

978 poster 

ACCURACY AND VALIDITY OF CORRECTIONS OF ISOCENTER 

USING BONY LANDMARK FUSION OR SURROGATE MARKERS IN- 

SIDE PROSTATE GLANDS - IMAGE GUIDED RADIATION THERAPY 

TREATMENT OF PROSTATE CANCER 

Z. Gao 1 , J. Wong 1 , S. Merrick 1 , M. Li 1 , M. Uematsu 2 , M. Lauterbach 3 , 

R. Stephenie 4 , C. W. Cheng 1 

1 

MORRISTOWN MEMORIAL HOSPITAL, Radiation Oncology, Morristown, NJ, 

USA 

2 

UAS ONCOLOGY CENTER, Radiation Oncology, Kagosima, Japan 

3 

SIEMENS MEDICAL SOLUTION, Oncology solutions, Concord,CA, USA 

4 

MORRISTOWN MEMORIAL HOSPITAL, Carol G. Simon Cancer Center, 

Morristown, NJ, USA 

Purpose: Two of the most commonly used image-guided radiation therapy 

(IGRT) techniques are: 1) bony landmarks, 2) implanted fiducial markers. 

Because neither of these methods take into account the actual positions and 

shape of the target or tumor volume at the time of treatment, they serve as a 

surrogate to the interfractional movements of the target. In our department, 

we have used in room CT in combination with linear accelerator for IGRT 

since year 2000. Over 400 patients and 3000 pre-treatment CT scans have 

been collected. We selected 10 patients with multiple intrinsic calcifications in 

the prostate glands for this study. The intrinsic prostate calcifications as seen 

in figure 1 function like implanted fiducial makers, except without migrations. 

CLINICAL/DISEASE SITES : PROSTATE 

S 311 

By retrospectively analyzing 144 CT scans obtained throughout the course 

of treatments in these 10 patients, we gained insight into the accuracy and 

validity of the two of most commonly used methods of IGRT. 

Materials: 10 patients with significant calcification in their prostate were retrospectively 

reviewed. Each patient was imaged via CT-on-rails for 15 fractions. 

A total of 144 valid scans were compared against their planning CTs. 

The method of CT-guided IGRT has been descibied previously. Using the CT 

scans obtained, we correct for the daily set up errors using two methods:1) 

Bony Landmark Fusion (BLF)the Pinnacle Syntegra R○system is utilized to 

automatically match the anatomy. 2) Intrinsic calcification (CF)all ten of these 

patients had multiple intrinsic calcifications scattered at different parts of the 

prostate glands. As such, their properties are similar to that of implanted 

fiducial markers. The CT data were manually fused by matching the calcifications. 

After applying both types of registrations, we examine how much the 

prostate gland is still varied from the planned isocenters. 

Results: In the lateral directions 13% and 3% shifts measured with BLF were 

off more than 3 and 5 mm respectively when the actual positioning is reviewed 

with the CT scans. For the CF group, 21% and 4% were off more than 3 and 

5 mm respectively against those measured with MPF. In the AP direction, for 

the BLF group, 38% and 19% were off more than 3 and 5 mm respectively. 

For the CF group, 26% and 10% were off more than 3 and 5 mm resectively. 

In the SI direction, for the BLF group, 19% and 10% were off more than 3 and 

5 mm respectively. For the CF group, 26% and 9% were off more than 3 and 

5 mm respectively. 

Conclusions: Although bony landmark fusion and fiducial markers are 

straightforward and quick to be performed, our data indicated that both methods 

may miss the ’corrected isocenter’ by 3mm or more for a substantial 

number of patients. Dosimetric considerations of these variations will be presented 

in the conference. Our data further implied that accurate and clear 

images of the prostate gland and normal tissue is a pre-requisite for performing 

IGRT. 

979 poster 

ACUTE AND CHRONIC TOXICITY OF HYPOFRACTIONATED RA- 

DIOTHERAPY IN TREATMENT OF INTERMEDIATE-RISK PROSTATE 

CANCER 

M. Di Genesio Pagliuca 1 , M. Di Staso 1 , P. Bonfili 1 , G. L. Gravina 1 , F. 

Soldà 1 , P. Franzese 1 , V. Tombolini 1 

1 UNIVERSITY OF L’AQUILA, Radiotherapy, L’Aquila, Italy 

Purpose: Radiobiological evidences suggested that prostatic cancer could 

be characterized by a low proliferation index and by an αMβ ratio of 1.5-4, 

lower than closer late responding normal tissues (rectal and vesical αMβ> 

4). This assumption could justify the use of higher doses per fraction, biologically 

equivalent to a conventional fractionation. We have evaluated the safety 

of hypofractionated radiotherapy assessing genitourinary (GU) an gastrointestinal 

(GI) toxicity from baseline to 6 months after treatment. 

Materials: Enrolled patients (pts) had one the following higher risk features: 

Gleason score 7, PSA at diagnosis > 10 ng/mL and < 20 ng/mL or T2b clinical 

stage. All pts received 6 months of hormonal therapy (HT) consisting of 

a gonadotropin-releasing hormone agonist. Total radiation dose was 5430 

cGy in 15 fractions, 3 times per week with 362 cGy per fraction. GU and GI 

symptoms were assessed at baseline, weekly during radiotherapy, at 2 and 4 

weeks after the end of radiotherapy and every 3 months thereafter. 

Results: Thirtyfive pts were recruited and the median follow-up was 30.5 

months (25.6-32.5). 21 pts (60%) experienced Grade 1 and 5 (14.3%) Grade 

II acute GU toxicity. None developed a Grade III-IV acute GU toxicity. At 3 

months, 2 pts (5.7%) had Grade I GU toxicity. At 12 and 24 months none 

experienced GU toxicity. Acute grades 0, I and II GI toxicity were detected 

respectively in 24 (68.6)%, 9 (25.7%) and 2 (5.7%) pts. No acute grade III or 

IV GI toxicity was recorded. At 3 months, 4 pts (11.4%) had Grade I GI toxicity. 

At 24 months there were still 1 (3%) pt with Grade I GI toxicity. No Grade 

II-III and IV GI toxicity was detected at 12 and 24 months. GU and GI symptoms 

assessment at baseline showed that, respectively, 5 pts (14.3%) reported 

daytime frequency > 8 micturitions, 20 pts (57.1%) reported nicturia > 

2 episodes per night, 5 pts (14.3%) had urgency more than occasionally, 8 pts 

(22.9%) reported slow stream more than occasionally, 3 pts (8.6%) had bowel


frequency > 3 stools/day, and 1 pt (3%) reported occasional rectal bleeding 

. The analysis of the same GU and GI symptoms at 6 months demonstrated 

that respectively, 4 pts (11.4%) reported daytime frequency > 8 micturitions, 

23 pts (65.7%) reported nicturia with > 2 episodes per night, 10 pts (28.6%) 

had urgency more than occasionally, 7 pts (20%) reported slow stream more 

than occasionally, 6 pts (17.1%) had bowel frequency more than 3 stools/day, 

and 3 pts (8.6%) reported occasional rectal bleeding rated. There was no evidence 

of differences in terms of bladder and bowel functioning at 6 months 

respect to the baseline values. The General Linear Model Regression analysis 

indicates that acute GU toxicity is influenced by the baseline degree of 

GU symptoms as only significant predictive factor. No other factors reached 

significance on the acute and late GU toxicity as well as on the late GU toxicity. 

Conclusions: Hypofractionated radiotherapy regimen associated to 6 

months of HT presents an acceptable toxicity. The small worsening detected 

in bladder and bowel functioning seems to be not clinically significant. 

980 poster 

ACUTE AND LATE TOXICITY OF HYPO-FRACTIONATED SIMULTA- 

NEOUS INTEGRATED BOOST TOMOTHERAPY OF 60 PROSTATE 

CANCER PATIENTS. 

N. Di Muzio 1 , C. Fiorino 2 , C. Cozzarini 1 , F. Alongi 1 , P. Mangili 2 , G. 

Berardi 1 , S. Broggi 2 , R. Calandrino 2 , F. Fazio 3 

1 SCIENTIFIC INSTITUTE SAN RAFFAELE, Radiotherapy, Milan, Italy 

2 SCIENTIFIC INSTITUTE SAN RAFFAELE, Physics, Milan, Italy 

3 SCIENTIFIC INSTITUTE SAN RAFFAELE, IBFM-CNR, Department of 

Nuclear Medicine, Radiotherapy, Milan, Italy 

Purpose: To evaluate acute and early late toxicity in patients( pts) with localized 

prostate cancer treated with moderately hypofractionated radiotherapy 

delivered by Tomotherapy Hi ART I-II 

Materials: Between January 2006 and December 2007, 60 pts. were evaluated. 

The median follow up was 10 months (3-25months) and median age 

was 75 years (60-84). According to NCCN class risk, 31/60 pts were considered 

low, 20/60 intermediate and 9/60 high risk. 29/60 received also pelvic 

lymph nodes irradiation. Different CTVs were defined: CTV1: Pelvic nodes 

(N); CTV2: 2/3 cranial portion of seminal vesicles (SV); CTV3: lower third of 

SV; CTV4: prostate; OP: overlap region between PTV4 and rectum. Different 

doses to each PTV, according with a grouping risk, were delivered in 28 

fractions: low risk: 56 Gy, 61.6 Gy and 71.4 Gy for PTV2-4 respectively; intermediate 

risk: 51.8 Gy, 61.6 Gy, 65.5 Gy and 74.2 Gy for PTV1-4 respectively; 

high risk: 51.8 Gy, 65.5 Gy for PTV1-2 and 74.2 Gy for both PTV3 and PTV4. 

For all patients the dose to OP was limited to 65.5 Gy 

Results: Acute and late toxicity were defined according to RTOG and 

RTOG/EORTC scoring system Acute GU toxicities were: 25/60(42%) G0, 

21/60(35%) G1, 12/60(20%) G2, 2/60(3%) G3. The median time to GU toxicity 

was 28 days (range 6-42). Acute rectal toxicities were: 42/60(70%) G0 

and 18/60(30%) G1, mainly proctitis. No patients experienced G2 acute rectal 

side effects. Median time to G1 proctitis was 27 days ( range:18-72days). 

Twelve(20%) pts showed upper intestinal (UI) toxicity with a median time to 

event of 28 days (6-41days), 5 of them received pelvic irradiation. They were 

all recorded as G1. 40/ 60 pts received also neoadjuvant and/or adjuvant hormone 

therapy . Considering the prescription dose we obtained two groups A 

and B: in 31 low risk (group A) and in 29 intermediate-high risk (group B) the 

cumulative doses were 71,4 Gy and 74,2 Gy respectively. Both these groups 

showed the absence of rectal and upper GI toxicity greater than G1. In 25 

pts with a minimum follow up of 12 months we recorded only 1G2 and 2G1 

proctitis. Up to now none experienced G3 or G4 toxicity. In the same group 

we reported GU toxicity as follow: 19 G0, 3 G1, 2 G2, 1 G3(urethral stenosis). 

All pts are bNED according to ASTRO failure criteria 

Conclusions: This phase I-II study shows excellent results of acute and 

early late GI toxicity rates. Moreover the GU acute and early late toxicity is 

comparable with those reported in other series with conventional/moderately 

hypofractionated schedules The Tomotherapy planning and delivery system 

provided improved dose distribution allowed for both lower median rectal dose 

and decreased dose to the intestinal cavity when the pelvic lymph nodes are 

included. Further follow up is needed to assess definitive late toxicity and 

tumour control outcome. 

981 poster 

ACUTE TOXICITY COMPARISON BETWEEN IMRT, TOMOTHERAPY 

AND 3DCRT IN THE TREATMENT OF PELVIC NODES DURING POST 

OPERATIVE RADIATION THERAPY FOR HIGH AND INTERMEDIATE 

LOCALIZED PROSTATE CANCERPATIENTS 

F. Alongi 1 , C. Fiorino 2 , C. Cozzarini 1 , L. Perna 2 , N. Di Muzio 1 , S. Broggi 

2 , R. Calandrino 2 , F. Fazio 3 

1 SCIENTIFIC INSTITUTE SAN RAFFAELE, MILAN, Radiotherapy, Milan, Italy 

2 SCIENTIFIC INSTITUTE SAN RAFFAELE, MILAN, Physics, Milan, Italy 

3 SCIENTIFIC INSTITUTE SAN RAFFAELE, MILAN, IBFM-CNR, Radiotherapy, 

Nuclear Medicine, Milan, Italy 

Purpose: To compare the incidence of acute genito-urinary(GU), upper 

gastrointestinal (uGI) and rectal (lGI) toxicity profile among three dimensional 

conformal radiotherapy (3DCRT), intensity modulated radiation therapy 

(IMRT) and Tomotherapy(TomoT), and in patients with localized carcinoma of 

the prostate (CaP) treated with prostatic bed (PB) and pelvic lymph-nodal 

(pLN) irradiation after radical prostatectomy (RP) . 

Materials: Between February 2004 and February 2008, 144 consecutive intermediate 

and high patients (pts) previously submitted to RP for a clinically 

localized CaP underwent PB+pLN irradiation in our Department for salvage 

or adjuvant intent. Out of the 144 patients, 80 underwent box 3DCRT, 19 5fields 

dynamic MLC IMRT (Varian system) with linear accelerator while 44 

were treated with Helical-Tomotherapy(Hi Art II) with a simultaneous integrated 

boost approach. The median age was 64.7 and 65,6 for 3DCRT and 

IMRT-TomoT group respectively. The median dose delivered to the PB was 

72.8 Gy (65.8-77.4) at 1.8Gy/fr in the 3DCRT group and 70.3 Gy (64.4-76) 

at 1.8-2.55Gy/fr in the IMRT TomoT group. The median dose delivered to 

the pLN was 50.1 Gy (45-54Gy) at1.8 Gy/fraction in the 3DCRT group and 

50.1 Gy (50-54 Gy) at 1.8-2 Gy/ fr in the IMRT-TomoT group. The median 

time from RP to RT was 397 and 429 days, respectively, (p=0,82, t-student 

test) in 3DCRT and IMRT-TomoT group. Acute GU, uGI e lGI toxicities after 

radiation treatment were evaluated and scored using RTOG/EORTC system. 

Dose-volume histograms of all patients were recovered for further analysis. 

Results: In patients treated with IMRT or TomoT a significantly lower incidence 

of the risk of acute GU, uGI and lGI injuries with respect to those who 

underwent 3DCRT was recorded. G2-3 GU toxicities were 6.3 % vs 12.5 % 

(p=0.21). For uGI, G2-3 toxicities were 4.8 % vs 22.5 % (p.0,0035). For lGI, 

G2-3 toxicities were 1.6 % vs 8.8 % (p=0.065). When comparing against TomoT 

only against 3DCRT, the differences slightly increased as follows: G2-3 

GU: 4.5 % vs 12.5 % (p = 0.15); G2-3 uGI: 2.3 % vs 22.5 % (p = 0.0034); 

G2-3 lGI: 0.0 % vs 8.8 % (p = 0.05). The average DVHs of rectum, bladder 

and intestinal cavity referred to the first 5-6 weeks of treatment show a dramatically 

improved sparing with IMRT-TomoT, especially for intestinal cavity. 

TomoT was shown to further spare these organs compared to Linac IMRT. 

Conclusions: The results of our study on a large sample of patients treated 

to pelvic nodes, shows that acute GU, uGI and IGI toxicities are significantly 

reduced with TomoT and IMRT when treating PB and pLN after radical prostatectomy. 

Longer term data are awaited for late toxicity profiles and clinical 

efficacy in TomoT and IMRT patients. 

982 poster 

ANALYSIS OF INTERFRACTION PROSTATE MOTION USING 

MEGAVOLTAGE CONEBEAM CT 

K. Bylund 1 , J. Bayouth 1 , M. Smith 1 , J. Buatti 1 

1 UNIVERSITY OF IOWA COLLEGE OF MEDICINE, Radiation Oncology, Iowa 

City, IA, USA 

Purpose: To determine the degree of interfraction prostate motion and its 

components as measured by daily megavoltage cone beam CT (MV CBCT) 

imaging. 

Materials: 984 daily MV CBCT images from 24 patients receiving definitive 

IMRT for localized prostate cancer were analyzed retrospectively. Pretreatment 

couch shifts, based on physician registration of MV CBCT to planning 

CT data sets, were used as a measure of daily interfraction motion. No 

bowel or bladder regimen was prescribed. Patients were immobilized using a 

deformable mold, and aligned with laser sights before daily MV CBCT imaging. 

Off-line bony registration was also performed using a mutual information 

algorithm to separate bony misalignment from internal organ motion. Group 

systematic (M), systematic (Σ), and random (σ) errors were calculated for 

total interfraction motion, bony misalignment, and internal prostate motion. 

Results: Mean vector interfraction prostate motion was 6.7 mm. Mean single 

axis displacements from zero were 4.9 mm (Anterior-Posterior, AP), 2.9 mm 

(Left-Right), and 2.1 mm (Superior-Inferior). The largest positional inaccuracy 

was accounted for by systematic deviations in bony misalignment. This was 

larger than systematic internal prostate motion (p < 0.001), and again largest 

in the AP direction (4.8 mm). Random deviations were due to relatively equal 

contributions from bony misalignment and internal prostate motion. Daily AP 

motion did not correlate with elapsed days since beginning therapy, either in 

the aggregate (R 2 = 0.12), or in individual patients (all R 2 < 0.15). Average 

AP motion was not correlated with planning rectal size near the prostate (R 2 

= 0.04), although 4 patients had planning rectal volumes of > 100 cc. Mean 

interfraction motion over the first six days of therapy, when used as a subsequent 

offset, reduced acceptable AP planning treatment volume margins 

(2.5Σ + 0.7σ ) by 40-55%. 

Conclusions: MV CBCT imaging showed significant interfraction motion with 

respect to conventional 3D conformal and IMRT margins. Large systematic 

deviations were seen in bony misalignment, which may be due skin changes, 

incorrect skin marking placement, or changes in muscle tone. Approximately 

half of the reduction in acceptable treatment margins associated with daily 

MV CBCT image guidance can be obtained after six daily images.

983 poster 

ARE THE DOSE ESCALATION TO MORE THEN 70 GY CAUSES 

INCREASED ACUTE AND LATE RECTAL AND BLADDER TOXICITY? 

H. Urbanczyk 1 , J. Ciechowicz 2 , L. Miszczyk 1 

1 

MSC MEMORIAL CANCER CENTER IN GLIWICE, Radiotherapy Dep., 


2 

MEDICAL UNIVERSITY OF LODZ, Computer Laboratory, Lodz, Poland 

Purpose: To evaluate the acute and late rectal and bladder toxicity for patients 

irradiated because of Prostate Cancer (PC). 

Materials: 161 non-operated PC patients, aged 50-79 (median 67), treated 

radically in the Radiotherapy Department, MSC Memorial Cancer Center in 

Gliwice, between 1996 and 2001. Patient were treated conformally, using 

mainly 20 MV photons (149 patients). Prescribed doses have been increasing 

from 60 Gy at the beginning to 74 Gy at the end of the aforementioned period. 

The degree of the experience in conformal radiotherapy of the medical team 

have been increasing too in this time. The median delivered dose was 70 

Gy. RTOG/EORTC scale were used for an evaluation of the acute and late 

rectal and bladder toxicity, 1 and 3 (acute), 6, 12, 18 and 24 (late) months 

after irradiation completion. 

Results: We did not observe any 4 score toxicity. Acute bladder toxicity of 

level 3 was observed for five patients one month after irradiation and for one 

of them two months later. Late bladder and rectal toxicities of 3 score were 

observed only incidentally. More than 80% patients have got 0 level of the 

late rectal and bladder toxicity and 0 level of the acute rectal toxicity. Only 

acute toxicity depends on prescribed dose. We find statistically significant 

correlation between total delivered dose and the degree of bladder toxicity 

score three months after irradiation (p=0,013) and between this dose and the 

level of rectal toxicity one month after treatment. 

Conclusions: The frequency of rectal and bladder toxicities were acceptable. 

Late toxicity is not depended on total delivered dose in analyzed group of 

patients. 

984 poster 

ASSESSING THE IMPACT OF A CLINICAL TRIAL PROTOCOL ON 

INTRA AND INTER-OBSERVER TARGET VOLUME CONTOURING 

FOR POST-PROSTATECTOMY RADIOTHERAPY 

J. Logue 1 , D. Mitchell 1 , L. Perry 2 , S. Smith 2 , T. Elliott 1 , R. Cowan 1 , J. 

Livsey 1 , J. Wylie 1 

1 CHRISTIE HOSPITAL, Clinical Oncology, Altrincham, United Kingdom 

2 CHRISTIE HOSPITAL, Radiotherapy Physics, North Western Medical 

Physics, Altrincham, United Kingdom 

Purpose: To compare post-prostatectomy clinical target volume delineation 

before and after the introduction of the MRC PR10 clinical trial contouring 

protocol. 

Materials: Six site specialised clinical oncologists were asked to independently 

delineate a clinical target volume on the CT images of 3 cases, previously 

treated with post-prostatectomy radiotherapy for pT3 disease, positive 

margins or a rising PSA. 3 weeks later the clinicians repeated the exercise but 

observed the MRC PR10 ’RADICALS’ trial contouring protocol recommendations. 

Volumes were assessed for inter and intra-physician variability pre and 

post-protocol, using the maximum volume ratio (maximum volume/minimum 

volume) and coefficient of variation (SD x 100/mean) to express differences 

in volume size and dispersal of volumes around the mean. 

Results: An increase in mean clinical target volume (CTV) from 40.7cm3 to 

53.9cm3 was noted as a result of complying with the protocol (table 1), with 

individual increases in the mean CTV of 65%, 15% and 24% for patient 1, 2 

and 3 respectively. The maximum volume ratio’s improved with the protocol, 

falling from 3.4 to 1.9 for case 1, from 4.5 to 1.8 for case 2 and from 3.1 to 


S 313 

2.4 for case 3. The coefficient of variation reduced for all cases as a result 

of the protocol. Greater consistency in voluming for 5 of the 6 clinicians was 

noted after introduction of the protocol. When the effects of the individual factors 

(doctors, patient’s and protocol) on the volumes were assessed using a 

three way analysis of variance, both the doctors (P=0.005) and the protocol 

(P=0.004) were significant factors in contributing to the variation, while the patient’s 

were not (P=0.45). When the effect of combined factors was assessed, 

no combination was found to be significant. 

Conclusions: There is substansial inter-observer variation in target volume 

delinaetion for post prostatectomy radiotherapy which can be reduced by the 

use of a contouring protocol. It also decreases intra-observer variability. The 

current MRC PR10 contouring protocol leads to an increase in the treatment 

volumes when compared to those typically applied at our centre. While the 

PR10 trial addressed the timing of adjuvant radiotherapy and use of hormonal 

manipulation, continued research is required to optimise the targeting of adjuvant 

radiotherapy and to develop prognositic nomograms aiding patient selection. 

985 poster 

AUTOMATIC CLASSIFICATION OF 3T-MR SPECTRA FOR PROSTATE 

CANCER LOCALISATION 

P. Oberhammer 1 , A. Gröger 2 , M. Blank 1 , M. Alber 3 

1 

SIEMENS AG MEDICAL SOLUTIONS, Imaging Science Institute Tübingen, 

Erlangen, Germany 

2 

UNIVERSITY OF TÜBINGEN, Department of Radiological Diagnostics, 

Tübingen, Germany 

3 

UNIVERSITY OF TÜBINGEN, Department of Radiation Oncology, Section for 

Biomedical Physics, Tübingen, Germany 

Purpose: A high degree of inter-patient variability and diffuse tumour growth 

pose problems for the classification of MR choline+creatine/citrate spectra. In 

order to determine a single dominant intra-prostatic lesion, different automatic 

classification algorithms were evaluated for MRSI voxel discrimination and 

compared with respect to robustness and performance. 

Materials: Using combined results of MR imaging and spectroscopy at 3T, tumour 

voxel discrimination was performed for 24 biopsy-proven prostate cancer 

patients with a total of 5868 voxels. 2018 voxels were classified as tumour, 

1180 probably tumour, 993 probably healthy and 1677 healthy. Based 

on metabolite concentrations following methods were used for differentiation: 

i) (Cho+Cr)/Cit ratio ii) Cho/Cit ratio iii) linear discriminant analysis (LDA) iv) 

neural network non-linear statistical data modelling v) support vector machine 

(SVM) maximum margin classifier. Additionally, local neighbourhood information 

is integrated by means of the Cho/Cit ratio. Performance was evaluated 

using a leave-one-patient-out cross-validation scheme and area under the 

receiver operating characteristic (ROC) curve as well as sensitivity (Se) and 

specificity (Sp). 

Results: For these methods the results for ROC curves were as follows: i) 

0.758 ii) 0.771 iii) 0.702 iv) 0.723 v) 0.693. Because of mostly diffuse tumour 

spread, long-time hormone deprivation therapy, and prostatitis only patients 

with local tumour focus were considered resulting in a total of 1470 voxels 

(104 tumour, 173 prob. tumour, 236 prob. healthy, 957 healthy). Areas under 

the ROC curves (Fig. 1) were as follows: i) 0.871 ii) 0.912 iii) 0.916 iv) 0.907 v) 

0.925. Following values for (Se, Sp) were obtained: i) 0.86, 0.71 ii) 0.89, 0.77 

iii) 0.87, 0.82 iv) 0.78, 0.88 v) 0.86, 0.86. Using adjacent voxel information for 

methods iii-v, the following results (ROC, Se, Sp) were obtained: iii) 0.926, 

0.90, 0.81 iv) 0.913, 0.87, 0.82 v) 0.928, 0.94, 0.80. 

Conclusions: For local tumour focus patients, all presented methods perform 

better than the established (Cho+Cr)/Cit ratio and can be used for automatic 

tumour discrimination in the clinical routine. Compared to the choline/citrate 

ratio, only LDA and SVM could slightly improve the classification performance, 

while neural networks were hard to control. Adding neighbourhood information 

resulted in a small improvement for SVM and LDA methods. Problems 

are present in patients with diffuse tumour spreading, long-time hormone deprivation 

therapy, and prostatitis, where tested automatic classification algorithms 

are not suitable for therapy decisions.


986 poster 

BIOCHEMICAL RECURRENCE AFTER STEREOTACTIC RADIATION 

THERAPY USING CYBERKNIFE TREATMENT OF LOCALIZED 


C. Choi 1 , C. Cho 1 , S. Yoo 1 , M. Kim 1 , H. Yoo 1 , K. Yang 1 , Y. Seo 1 , J. 






Purpose: Herein is reported our initial experience of the CyberKnife to show 

its safety and feasibility as a treatment modality for localized prostate cancer. 

Materials: Between August 2002 and November 2005, 44 patients, with 

biopsy-proven prostate cancers, who treated with CyberKnife were enrolled 

in this study. The patients were divided into three risk groups: low (pretreatment 

PSA < 10 ng/ml and Gleason score ≤ 6 and Stage T1b T2a); high 

(pretreatment PSA ≥ 20ng/ml or Gleason score ≥ 8); and intermediate (all 

other patients). Ten patients of 44 were low, 9 were intermediate, and remaining 

25 patients were high risk group. The median age was 70 years (range 52 

79) and the median follow-up duration was 13 months (range 4 46 months). 

All patients except 1 had received CK treatment with total doses of 32 36 Gy 

in 4 fractions. One patient had received CK treatment with doses of 24 Gy 

in 3 fractions. The biochemical failure free survival rate and overall survival 

rate were analyzed according to Kaplan-Meier method. The biochemical failure 

was evaluated by ASTRO definition and modified ASTRO definition. The 

acute toxicities of rectum and urinary bladder were also evaluated using the 

acute toxicity score of the Radiation Therapy Oncology Group (RTOG). The 

results of acute toxicities were compared to those of the historical control, 

which had been treated with conventional four field box technique. 

Results: The 3-year biochemical failure free and overall survival rate by AS- 

TRO definition and modified ASTRO definition were 75.4% and 100% and 

78.8% and 100%, respectively. Fourteen and 17 patients had experienced 

grade 1 or 2 acute toxicities of rectum and urinary bladder, respectively. However, 

there were no severe acute toxicities more than grade 3. All toxicities 

were controlled spontaneously or with medications within 3 months after treatment. 

Conclusions: The results of CK treatment for localized prostate cancer were 

comparable with those of IMRT or 3D CRT. Moreover, the short treatment 

period compared to conventional radiotherapy would provide convenience to 

patient with increment on quality of life. So, CK treatment could be adopted 

as an option for treatment for localized prostate cancer. 

987 poster 

CARBON ION THERAPY FOR PROSTATE CANCER SEEMS COST- 

EFFECTIVE IN THE LONG TERM WHEN QUALITY OF LIFE IS 

TAKEN INTO ACCOUNT, BUT MORE EVIDENCE IS STILL NEEDED 

A. Peeters 1 , M. Joore 2 , M. Pijls-Johannesma 1 , D. De Ruysscher 1 , A. 

Dekker 1 , J. Grutters 1 , S. Reimoser 3 , J. Severens 4 , P. Lambin 1 

1 MAASTRO CLINIC, Radiation Oncology, Maastricht, Netherlands 

2 UNIVERSITY HOSPITAL MAASTRICHT, MAASTRO CLINIC, Department 

of Clinical Epidemiology and Medical Technology Assessment, Maastricht, 

Netherlands 

3 TURNER & TOWNSEND GMBH, Munchen, Germany 

4 UNIVERSITY HOSPITAL MAASTRICHT, MAASTRO CLINIC, Department of 

Health Organization, Policy Economics, Maastricht, Netherlands 

Purpose: Therapy with charged particles, protons and carbon ions (c-ions), 

is a promising modality to treat prostate cancer. It offers improved dose distributions 

to the target volume as compared to conventional radiotherapy, with 

better sparing of surrounding healthy tissues. However, the costs of particle 

therapy are high compared to photon therapy and it is unclear whether the 

extra effects are worth the extra costs. A cost-effectiveness of particle therapy 

as opposed to the best current external beam radiotherapy (EBRT) with 

photons was examined. 

Materials: In a cost-effectiveness Markov model two treatment strategies (for 

the moment), with c-ions and photons, were evaluated. Therapy effects were 

simulated for a cohort of 70 year old males with locally advanced prostate 

cancer eligible for curative EBRT. The outcomes were survival, quality adjusted 

survival and costs. The therapy effects and quality of life estimates 

were derived from the literature. The c-ion estimates were based on the outcomes 

from the NIRS Institute, Chiba, Japan. Photon therapy estimates were 

based on treatment with intensity modulated radiation therapy (IMRT). Toxicity 

of treatment was taken into account. Direct medical costs were assigned. 

The time horizon of the model was 10 years. The study was performed from 

the health care perspective. 

Results: Preliminary results showed that c-ion treatment leads to better clinical 

effects but more costs. The expected total health care costs per patient 

over 10 years were e22 880 for c-ion and e13 550 for photon therapy. The 

expected life years were 8,78 and 8,68, respectively. The difference in the 

clinical effects became larger, when quality of life was accounted for. The 

quality of life adjusted life years (QALY’s) were 7,82 for c-ion and 7,59 for 

photon therapy. Extra costs per QALY gained were e40 170 (up to 65 000 in 

a sensitivity analysis). 

Conclusions: The preliminary results indicate that with a threshold of e80 

000 per QALY, treatment with c-ions is cost-effective (for 70 years old, within 

10 years). The model will be further adapted. Firstly, treatment with protons 

will be added and included in the cost-effectiveness analysis. Secondly, analyses 

will be performed for different age and risk categories (based on T stage, 

Gleason score and initial PSA value). Thirdly, the probability that the different 

treatment modalities are cost-effective, given the existing uncertainty, will be 

assessed. Finally, it will be determined whether future research is needed to 

reduce existing uncertainty and for which parameters such research would be 

most valuable according to an expected value of perfect information (EVPI) 

analysis. 

988 poster 

CLINICAL AND DOSIMETRIC PREDICTORS OF ACUTE TOXICITY 

AFTER A FOUR-WEEK HYPOFRACTIONATED EXTERNAL BEAM 

RADIOTHERAPY REGIMEN FOR PROSTATE CANCER: RESULTS 

FROM A MULTICENTRIC PROSPECTIVE TRIAL 

S. Arcangeli 1 , L. Strigari 2 , G. Soete 3 , G. De Meerleer 4 , S. Gomellini 1 , V. 

Fonteyne 4 , G. Storme 3 

1 

REGINA ELENA NATIONAL CANCER INSTITUTE, Radiotherapy, Rome, Italy 

2 

REGINA ELENA NATIONAL CANCER INSTITUTE, Laboratory of Medical 

Physics and Expert Systems, Rome, Italy 

3 

RADIOTHERAPY ONCOLOGY CENTER UZB, Radiotherapy, Brussels, 

Belgium 

4 

GHENT UNIVERSITY HOSPITAL UZG, Radiotherapy, Ghent, Belgium 

Purpose: To investigate predictors for gastrointestinal (GI) and genitourinary 

(GU) acute toxicity after a short course hypofractionated radiotherapy regimen 

for prostate cancer. 

Materials: Three institutions (IRE, UZB, GUH) included 102 patients with 

T1-T3N0M0 prostate cancer in a phase II study. Patients were treated with 

56 Gy in 16 fractions over 4 weeks. Acute toxicity was scored using the 

RTOG/EORTC criteria extended with additional symptoms, and the international 

prostate symptom index (IPSS) weekly during treatment and 1 and 2 

months afterwards. The correlation with a number of clinical and dosimetric 

parameters was assessed by univariate and multivariate analyses. 

Results: No grade 3 or 4 Gastro-intestinal (GI) side effects were observed. 

Grade 1 and grade 2 rectal GI toxicity occurred in 36%, and 38%, respectively. 

The corresponding figures for grade 1 and grade 2 Genito-urinary 

(GU) toxicity were 42% and 39%, respectively. A grade ≥ 3 GU toxicity was 

detected in 4% of patients. In multivariate analysis, percent rectal volumes 

higher than 8% receiving doses ≥ 53 Gy (V53) were statistically correlated 

to G2 acute rectal reaction (p=0.006). For GU morbidity, only the IPSS pretreatment 

score was independently associated (p=0.0036) with an increase 

in GU acute effects. 

Conclusions: Both acute GU and GI toxicity are comparable with other series. 

Our data show that the increase in the incidence and intensity of acute 

toxicity is a transient effect related to the shorter overall treatment time rather 

than a larger effect in biological equivalent dose with respect to a conventional 

fractionation regime. 

989 poster 

CLINICAL APPLICATION OF DYNAMIC CONTRAST ENHANCED 

MAGNETIC RESONANCE IMAGING (DCE MRI) FOR THE LOCAL-

IZATION OF RECURRENT PROSTATE CANCER. 

M. Moman 1 , E. Roeloffzen 1 , N. van den Berg 1 , U. van der Heide 1 , M. van 

Vulpen 1 


Purpose: Local recurrences after radiotherapy for prostate cancer are detected 

by PSA measurements in combination with prostate biopsy. In order 

to improve salvage treatment, and as a guide for biopsy procedures, there 

is a need for more accurate localization of recurrent tumour. A few studies 

show promising results regarding tumour detection using dynamic contrast 

enhanced magnetic resonance imaging (DCE MRI). The aim of this study 

was to investigate the clinical advantages of using DCE MRI in the detection 

of local recurrences after radiotherapy for prostate cancer. 

Materials: We describe the evaluation of 11 patients with a biochemical recurrence 

after radiotherapy for prostate cancer in the University Medical Center 

Utrecht. All patients underwent a DCE MRI and if indicated this was followed 

by prostate biopsy. The DCE MR images, based on the parameter 

K trans , were analysed and compared with the patient’s clinical information for 

further treatment decisions. No biopsy was performed in patients with no area 

suspect for tumour on DCE MRI. 

Results: DCE MR images showed areas with relatively increased perfusion 

in 6 patients (figure 1). In 2 patients of this group no biopsy was performed; 

in one because of a very short time since treatment and a decreasing PSA 

level at follow up, and in the other patient biopsy was postponed because of 

an alternating blood PSA level reacting on antibiotics, and subsequent suspicion 

for prostatitis. In the remaining 4 patients, 1 patient was treated primary 

by brachytherapy (140 Gy), 2 by intensity modulated radiotherapy (IMRT, 76 

Gy) and 1 by conventional external beam radiation (70 Gy). Median age at 

diagnosis was 63 years (range 60 67). Initial tumour stage was T3 in 3 patients 

and T2 in 1 patient. Tumours were well differentiated in 2 patients and 

moderately differentiated in 2 patients. Pre-treatment PSA ranged from 7.2 

to 30.0 ng/ml. PSA-nadir after treatment ranged from 0.3 to 7.5 ng/ml. The 

median time to biochemical recurrence was 28 months. Within suspected tumour 

areas on DCE MRI, the mean values of K trans were approximately twice 

the background level. Values ranged from 0,15 to 0,30 ml/min/cm3 for normal 

tissue, and 0,35 to 0,65 ml/min/cm3 for suspected areas. Biopsies from 

the suspected areas showed adenocarcinoma in all 4 cases, with Gleason 

scores of 6, 7, 7 and 7. Based on these findings, all patients were treated 

with salvage therapy; 3 by cryoablation and 1 by prostatectomy. 

Conclusions: These results show that in the clinical practice of radiation 

oncology, DCE MRI can contribute to the detection and localization of local 

recurrences of prostate cancer. More exact tumour localization could make 

localized salvage treatment possible, for example localized brachytherapy or 

IMRT on the tumour area. Further research is needed concerning threshold 

definition of DCE parameters, validation of DCE MRI and experience with 

localized salvage therapy. 

990 poster 


S 315 

CLINICAL IMPLEMENTATION OF IMAT PROSTATE TREATMENT 

USING ELEKTA SYNERGY 

K. Shiraishi 1 , K. Nakagawa 1 , A. Haga 1 , K. Ohtomo 1 , Y. Okano 1 , T. 

Oritate 1 , K. Yoda 2 

1 UNIVERSITY OF TOKYO HOSPITAL, Department of Radiology, Tokyo, Japan 

2 ELEKTA KK, Medical Physics, Kobe, Japan 

Purpose: Intensity modulated arc therapy (IMAT) for prostate treatment using 

ERGO++ treatment planning system and Elekta internal multi-leaf collimator 

(MLC) has been clinically implemented. 

Materials: An IMAT plan was made by ERGO++ and Elekta internal MLC. 

Dose was delivered to a water phantom in a cylindrical acrylic enclosure. The 

isocenter dose was measured by a pin-point chamber, which was compared 

to the calculated isocenter dose. An EDR2 film was placed inside a multi-layer 

acrylic phantom to obtain relative dose distributions, which were compared to 

calculated dose distributions. Subsequently, IMAT beams were delivered to 

prostate cancer patients. ERGO++ provides a static arc modulation (SAM) for 

a linac controller where MLC cannot be moved during gantry rotation, which 

was used for our clinical study. A full-angle arc was divided into many small 

arcs (hereinafter, referred to as "sub-arcs"), each of which has an optimized 

MU when ERGO++ inverse planning is completed. 

Results: The isocenter dose discrepancy was 1.7 % and the corresponding 

isodose contour distance between measurement and calculation for a range 

of over 50% of prescribed dose was mostly less than 2 mm. The on-axis dose 

profile discrepancy was generally less than 3 % for a range of over 50 % of the 

prescribed dose. By the time of writing, 5 patients have been treated by IMAT. 

The beam-on time was approximately 10 minutes because MLC leaves were 

moved between two successive sub-arcs each time after beams is turned off. 

Conclusions: We have successfully implement IMAT delivery using Elekta 

Synergy and internal MLC for prostate treatment. 

991 poster 

CLINICAL OUTCOME IN PATIENTS WITH PROSTATE CANCER 

TREATED WITH HIGH DOSE-RATE 192-IRIDIUM BRACHYTHERAPY 

AS MONOTHERAPY 

M. Ryberg 1 , E. Castellanos 1 , M. Hjelm-Eriksson 1 , G. Cohn-Cedermark 1 , 

A. Valdman 1 , A. Ullén 1 , J. Nilsson 2 , M. Lundell 2 , G. Lundell 1 , S. Nilsson 

1 , K. M. Kälkner 1 



Purpose: High dose rate (HDR) brachytherapy as monotherapy has been 

suggested to be an option in the treatment of localized prostate cancer. 

Prostate cancers are supposed to have low alpha/beta ratio and therefore 

be suitable to treatment with few fractions at high doses. We now report the 

feasibility for this type of treatment to patients with localized carcinoma of the 

prostate. 

Materials: From 2004 through mid 2007, 20 patients with localized prostate 

cancer were treated with two HDR brachytherapy sessions, 2 weeks apart, 

delivering 15 Gy to the planning target volume (PTV) defined as the prostate 

gland including the base of the seminal vesicles + 3 mm margin. The dose 

to the inner surface of the rectal wall was always kept below 60% of the prescribed 

dose of 15 Gy. The volume of the urethra was defined during the 

preplanning examination by the area of an 18 Gauge Foley catheter located 

in the urethra in each image throughout the length of the prostate gland. The 

acceptable maximum dose to the urethra volume was 15.5 Gy. The end point, 

no biological evidence of disease (bNED), was defined at PSA levels nadir + 

2 µg/L. Early side effects were assessed according to the RTOG scale for 

urinary tract and lower gastrointestinal tract symptoms. 

Results: 18 of the 20 assessable patients are bNED after a median followup 

of 24 months (range 3-42 months). One of the two patients developed 

an apparent PSA relapse with an increase of PSA to 6.9 µg/L. An aspiration 

biopsy from the prostate was performed for cytology, with no cancer cells 

recognised. The PSA has since decreased to 1.4 µg/L with no signs of progression 

during 34 months of follow-up. The second patient disclosed a PSA 

at 2.1 µg/L at 40 months follow-up. No patient experienced early rectal toxicity 

RTOG grade 3. Early urinary tract toxicity RTOG grade 3 was documented 

in 5 of the patients. The side-effects decreased over time but is still ongoing 

after 24 months in one patient who performs intermittent catheterisation. The 

presence of toxicity over time is demonstrated in figure. 

Conclusions: HDR used as monotherapy produces promising clinical results. 

Rectal toxicity is acceptable. The urinary tract toxicity is most likely the 

limiting factor for HDR as monotherapy, but further follow-up and evaluation is 

necessary. We have now increased the time between the treatments to three 

weeks and reduced the accepted maximal dose to the urethra to 15 Gy


992 poster 

CLINICAL VALUE OF [11C]-CHOLINE PET FOR THE DETECTION 

OF RECURRENCE IN PATIENTS WITH PSA RELAPSE AFTER EBRT 

FOR PROSTATE CANCER 

A. Breeuwsma 1 , J. Pruim 2 , F. van den Bergh 3 , R. Dierckx 2 , R. Nijman 4 , 

I. J. de Jong 4 

1 

UNIVERSITY MEDICAL CENTER GRONINGEN, Department of Urology/ 

Nuclear Medicine and Molecular Imaging, Groningen, Netherlands 

2 

UNIVERSITY MEDICAL CENTER GRONINGEN, Department of Nuclear 

Medicine and Molecular Imaging, Groningen, Netherlands 

3 

UNIVERSITY MEDICAL CENTER GRONINGEN, Radiotherapy, Groningen, 

Netherlands 

4 

UNIVERSITY MEDICAL CENTER GRONINGEN, Urology, Groningen, 

Netherlands 

Purpose: An elevated serum PSA level alone cannot distinguish between 

local, regional recurrences and the presence of distant metastases after curative 

treatment for prostate cancer. With the advent of salvage treatment 

such as cryotherapy, it has become important to localise the site of recurrence 

(local or distant). In this study the potential of 11 C-choline positron 

emission tomography (PET) to identify site of recurrence was investigated in 

patients with rising PSA after external beam radiotherapy (EBRT). 

Materials: 63 patients with histologically proven prostate cancer treated with 

external beam radiotherapy with curative intent and showing biochemical recurrence 

as defined by American society for Therapeutic Radiology and Oncology 

(ASTRO) consensus statement were included. Additionally, 7 patients 

without recurrence underwent a PET scan. After receiving 400 MBq 

11 C-choline intravenously a scan was made using an ECAT HR+ camera. 

Attenuation-corrected images were made using an iterative reconstruction algorithm 

(ordered subset expectation maximisation). As reference we used 

biopsy-proven histology from site of suspicion, positive findings with other 

imaging modalities, clinical follow-up and/ or response to adjuvant therapy 

expressed through PSA decline. 

Results: None of the patients without biochemical recurrence had a positive 

PET scan (no false positives). 50/ 63 patients with biochemical recurrence 

(median PSA 9 ng/ mL; mean PSA 12.5) showed abnormal uptake with PET 

(sensitivity 79%). Site of recurrence was only local in 39/ 50 patients (mean 

PSA 8.9 ng/ mL at scan), 9/ 50 patients locoregionally (mean PSA 12.7 ng/ 

mL) and 2/50 distant metastases (mean PSA 16,4 ng/ mL). Overall positive 

predictive value and negative predictive value for 11 C-choline PET was 1.0 

and 0.35 respectively. 

Conclusions: 11 C-choline PET scan is a sensitive technique to identify the 

site of recurrence in patients with PSA relapse after EBRT for prostate cancer. 

It can be a valuable tool in selecting candidates for local salvage treatment. 

993 poster 

CO-MORBIDITY AND THE RISK OF SIDE-EFFECTS AFTER 

COMBINED EXTERNAL RADIOTHERAPY AND HIGH DOSE RATE 

BRACHYTHERAPY IN PATIENTS WITH LOCALIZED PROSTATE 

CANCER 

K. Sandberg 1 , G. Cohn-Cedermark 1 , M. Hjelm-Eriksson 1 , E. Castellanos 

1 , A. Ullén 1 , J. Nilsson 2 , M. Lundell 2 , G. Lundell 1 , U. Harmenberg 1 , S. 

Nilsson 1 , K. M. Kälkner 1 



Purpose: Diabetes and vascular disease has been regarded as risk factors 

for developing side effects after radiotherapy. Using our experience from 

treatment of localized prostate cancer with conformal external radiotherapy 

combined with a high dose-rate (HDR) brachytherapy boost we conducted a 

retrospective study on co-morbidity impact on the risk of side-effects. 

Materials: From 1998 to 2002, 668 patients with localized prostate cancer 

received neoadjuvant hormonal therapy and external radiotherapy combined 

with 2 fractions of transperineal-approach HDR brachytherapy with transrectal 

ultrasound guidance. The patients completed a questionnaire prior to the 

medical visit at Radiumhemmet. The patient was asked to write down if they 

have been hospitalized previously, the presence of any disease with on-going 

controls and the actual intake of pharmaceutical. This questionnaire was 

complemented by the physician’s questions and noted in the medical chart. 

Retrospectively, one person read all the charts and patients self assessed 

questionnaire to assess co-morbidity according to Charlson score. From this 

score we extracted patients with diabetes and vascular disease. A medical 

history of hypertonia, angina pectoris, history of coronar heart infarction, TIA, 

and coronar by-pass surgery was assessed as vascular disease. Side-effects 

were assessed according to RTOG. 51 patients were lost of follow-up. 

Results: During an average follow-up at 4.5 years (range 0.5 to 9.2 years) 58 

patient died and 40 of these patients died without evidence of prostate cancer. 

The number of patients with diabetes was 53 (9%), with a vascular disease; 

243 (39%) and with a combination of diabetes and vascular disease; 38 (6%). 

During follow-up 17 patients and 100 patients developed RTOG grade 3 toxicity 

from intestinal tract and urinary tract, respectively. No difference was 

found in proportion of patients developing grade 3 toxicity from urogenital 

tract among patients with or without diabetes (9 out of 53 and 91 out of 564, 

respectively). Neither did the toxicity differ among patients who had vascular 

disease compared to those patients without vascular disease. 

Conclusions: Co-morbidity assessed according to principles of Charlson 

score can’t identify patients at increased risk for developing side effects 

graded according to RTOG score. 

994 poster 

CO-MORBIDITY AS AN IMPORTANT PROGNOSTIC FACTOR IN THE 

CLINICAL OUTCOME OF PATIENTS WITH PROSTATE CANCER 

TREATED WITH EXTERNAL BEAM RADIOTHERAPY AND HIGH 

DOSE-RATE 192-IRIDIUM BRACHYTHERAPY BOOST. 

M. Hjelm-Eriksson 1 , E. Castellanos 1 , G. Cohn-Cedermark 1 , K. Sandberg 

1 1 2 2 1 1 

, A. Ullén , E. Bengtsson , G. Lundell , S. Nilsson , S. Levitt , K. M. 

Kälkner 1 

1 


2 


Purpose: 50% of patients with prostate cancer are older than 70 years at 

diagnosis. With increased age the co-morbidity will inevitably increase. This 

is an important fact when deciding treatment modalities for localized prostate 

cancer. The contemporary view is that eligibility for radical treatment should 

remain restricted to patients assumed to have a life expectancy of at least 

10 years.Using our experience from treatment of localized prostate cancer 

with conformal external radiotherapy combined with high dose-rate (HDR) 

brachytherapy boost, we have now conducted a retrospective study on the 

impact of co-morbidity on prognosis. 

Materials: From May 1998 through Dec 2001, 503 patients with localized 

prostate cancer received neoadjuvant hormonal therapy and external radiotherapy 

combined with 2 fractions of HDR brachytherapy administered using 

a transperineal approach with transrectal ultrasound guidance. The patients 

completed a questionnaire prior to their first medical visit at Radiumhemmet. 

They were asked to write down if they had been hospitalized previously, the 

presence of any disease with on-going controls and the actual intake of pharmaceuticals. 

This questionnaire was complemented by the physician’s questions 

and noted in the medical chart. Retrospectively, one person read all 

the charts and the patient’s self assessed questionnaire to create a Charlson 

score. The Charlson score is a weighted index and consists of a list of 19 

conditions. 

Results: 74 patients have died during a mean follow-up of 5.8 years (range 

1-9 years). Ten patients were lost at follow-up. In 41 cases, the cause of 

death was not related to the prostate cancer but in the remaining 33 cases either 

a PSA-relapse or a progressive prostate cancer was documented before 

death. The co-morbidity according to the Charlson score is demonstrated in 

table.Co-morbidity score, clinical T-stage), PSA levels at diagnosis and grade 

of differentiation (high, middle or low grade) was used in a Cox proportional 

hazards regression model. The total co-morbidity score remains independently 

associated to overall survival after adjusting for T-stage, WHO grade 

and PSA (dichotomised to 20 ng/mL) as prognostic factors with Hazards ratio 

1,33 (confidence interval 1.11-1.59). 

Conclusions: Co-morbidity assessed according to Charlson’s score can 

identify patients with increased risk for early death. The co-morbidity should 

be considered when treatment options are discussed with the patient.

995 poster 

COMPUTER GENERATED IMAGE GUIDANCE IMPROVES EARLY 

SIDE EFFECTS IN INTRA-OPERATIVE PROSTATE BRACHYTHER- 

APY 

S. Husain 1 , S. Angyalfi 1 , P. Dunscombe 2 , D. A. Radford 2 , I. Kay 2 , T. 

Meyer 2 

1 

TOM BAKER CANCER CENTER, Radiation Oncology, Calgary, Alberta, 

Canada 

2 

TOM BAKER CANCER CENTER, Medical Physics, Calgary, Alberta, Canada 

Purpose: To demonstrate that an image guided intra-operative planning and 

automated delivery system, using ultrasound guided needle placement employing 

a sagital view results in consistently high post-operative D90’s with an 

acceptable and low rate of acute and sub-acute side effects. 

Materials: In our institute over 300 patients have had prostate brachytherapy 

performed using an intra-operative planning and delivery system (FIRST R○). 

Of these, 172 patients have more than 24 months of follow up (range 24-56 

months) and we report on these patients. The prescribed reference dose was 

144Gy to the prostate plus 3-5 mm margin. Average seed activity was 0.434 

mCi (range 0.35-0.52 mCi). Planning parameters were V100 >98%, V150 

(65 to 70%), V200 (30%) for the first 30 patients. After the first 30 implants 

our planning parameters were increased to: V100 > 99%, V150 (75 to 80%), 

V200 (35 to 40%) and intra-op D90 >190 Gy. Urethral, rectal and erectile 

function, were monitored by the AUA/IPSS score, rectal bleeding, diarrhea 

and the need for PDE5 inhibitors. Intra-op and Post-op dosimetry inculded 

D90, V100,V150 and V200. 

Results: The mean D90 planned intra-operatively was 194.4Gy (171.3- 

213.8Gy) and we noticed an average drop in D90 of 27.3 Gy. The postimplant 

mean parameters were D90 of 158.5Gy (Range 152Gy 182.7Gy) and 

V100 of 93.8% (Range 90.1% to 98.3%). Out of the 172 patients evaluated 1 

person developed an acute urinary obstruction requiring catheterization and 1 

patient developed a urinary stricture at 30 months requiring a dilatation. The 

mean IPSS score at baseline was 6.8 (range 0-26); 3 months 13.8 (range 

1-35), 12 months 7.9 (range 0-35). 23/172 (13.2%) patients required treatment 

for dysuria within the first 6 months and 17/172 (9.8%) developed symptoms 

between 9 and 24 months post treatment consistent with a urinary flare 

syndrome. Only 1 patient developed long term dysuria which settled at 20 

months post implant. Short term diarrhea was reported in 15/172 (8.7%), and 

bleeding occurred in 2/172 patients (1.2%) that resolved spontaneously within 

3 months. No late rectal symptoms have been reported. 79/129 evaluable 

patients (61.8%) were potent without assistance pre implant. 18/79 patients 

(22%) have subsequently required assistance with a PDE5 inhibitor such as 

Viagra, and all report satisfactory sexual function. Age < 65 predicted for use 

of PDE5 inhibitors post treatment (p=0.0061). 16/129 patients (12.5%) were 

using assistance pre implant and all report no change. It is early to report on 

PSA however the average PSA at baseline was 5.74 ng/ml, 6 months 1.33 

ng/ml, and 24 months 0.78 ng/ml. 

Conclusions: Computer guided intra-operative prostate brachytherapy allows 

for consistent intra-operative planning parameters that result in good 

post-op parameters with a reasonable range of D90 (30Gy) and V100 (8.2%). 

There appears to be a low overall acute urinary and rectal toxicity with a lower 

than average erectile dysfunction rate than reported in the literature. In a previous 

study we have shown that an intra-operative D90 of >190 Gy results in 

a or = T2c, PSA > 20 ng/ml, or Gleason score > or = 8) treated 

with HDR-BT combined with EBRT between July 1999 and Marchr 2006 at 

Kochi Medical School Hospital in Japan. Patient age ranged from 61 to 81 

years (median 72). Thirteen patients had received neoadjuvant hormonal 

therapy, which was stopped at the beginning of radiotherapy in all cases. Patients 

in this series were treated on three protocols. In the initial protocol, 8 

patients were treated with whole pelvis EBRT to 45 Gy in 25 fractions and 

HDR brachytherapy to 18 Gy in 3 fractions. In the second protocol, 8 patients 

were treated with prostatic EBRT to 40 Gy and HDR brachytherapy to 

18Gy in 3 fractions. In the third protocol, 8 patients were treated with prostatic 

EBRT to 40Gy and HDR brachytherappy to 18Gy in 2 fractions. In the 

first 12 patients, HDR-BT was planned by using two different oriented pelvic 

radiographs, and in the rest of patients, HDR-BT was planned by using CT 

images. Adjuvant hormonal therapy was not performed until biochemical failure 

or clinical recurrence became apparent. We used the American Society 

for Therapeutic Radiology and Oncology consensus definition for biochemical 

failure. Acute and chronic toxicities were scored using the Radiation Therapy 

Oncology Group guidelines. Follow-up ranged from 24 to 105 months (median, 

84 months). 

Results: The 3 and 5-year biochemical control rate was 87.1% and 80.4%, 

respectively. The 3-year overall, cause-specific, and disease-free survival 

rate was 85.6%, 100%, and 91.7%. The 5-year overall, cause-specific, and 

disease-free survival rate was 78.5%, 91.7%, and 84.0%. Two patients, who 

were treated with whole pelvis EBRT to 45 Gy and radiography-based HDR- 

BT, experienced Grades 3 and 4 late radiation toxicities for the gastrointestinal 

system, respectively. Grade 3 urethral stricture was observed in one patient. 

Acute toxicity has been modest. 

Conclusions: HDR-BT combined with EBRT is a very effective treatment for 

localized high risk prostate cancer. However, in order to achieve more reliable 

results, additional long-term follow-up is required. 

998 poster 

CYBERKNIFE TREATMENT FOR LOW AND INTERMEDIATE RISK 

LOCALIZED PROSTATE CANCER 

G. Bolzicco 1 , E. Scremin 2 , M. S. Favretto 1 , C. Tambone 2 , C. Cavedon 

3 , P. Scalchi 3 , G. A. Panizzoni 1 , C. Baiocchi 1 , A. Testolin 1 , C. Mari 1 , F. 

Messina 1 , A. Tasca 2 , P. Francescon 3 , R. Guglielmi 1 

1 S. BORTOLO HOSPITAL, Radiation Oncology, Vicenza, Italy 

2 S. BORTOLO HOSPITAL, Urology, Vicenza, Italy 

3 S. BORTOLO HOSPITAL, Medical Physics, Vicenza, Italy 

Purpose: Evaluation of the acute toxicity and kinetics of prostate specific 

antigen (PSA) in patients with prostate cancer treated with stereotactic body


radiation therapy (SBRT) by the CyberKnife R○System. 

Materials: From August 2006 to March 2008 15 patients were enrolled due 

to their age (mean 72 years) or inoperability. For these patients there was 

a histological diagnosis of prostate adenocarcinoma in stage T1b-T2c. Eight 

patients were started on hormone treatment prior to radiation treatment. The 

average PSA value was 7.9 ng/ml; in three patients it was more than 10 

ng/ml. The Gleason score was 7 (3+4) in 2 patients, 6 (3+3) in 12 patients 

and 5 (2+3) in 1 patient. The mean prostate volume was 33.1 cc (range, 20.5 

cc 45 cc). Four gold fiducials were implanted in each patient to allow imageguided 

treatment. During treatment patients were supine in a vacuum bag, 

their bladders filled with 80-100 cc of physiological solution, and the ampulla 

of the rectum was empty. The planning target volume (PTV) was constructed 

to deliver 35 Gy to the 80% isodose line in 5 equal fractions. 

Results: All 15 patients completed the treatment, and have an average 

follow-up of 8 months (2-20 months). Acute rectal (GI) and urinal toxicity (GU) 

were evaluated using the acute toxicity score of Radiation Therapy Oncology 

Group (RTOG): 5 patients had Grade 1 and 5 Grade 2 of GU/GI toxicity. No 

GU or GI toxicity higher than Grade 2 was found. The PSA value was determined 

30 days after treatment and then every three months. A progressive 

decrease in PSA was observed : mean 1,3 ng/ml at 3 months and 0,5 ng/ml 

at 6 months. 

Conclusions: CyberKnife treatment with 35 Gy in 5 fractions proved to be 

feasible, well tolerated, and resulted in good short-term control of PSA values. 

This is a treatment which, due to the absence of serious complications 

and the short time for the delivery, could be recommended as an alternative 

treatment option for localized prostate cancer in state T1b-T2c, low Gleason 

score (

lance, avoiding premature and inappropriate initiation of salvage therapy during 

a PSA bounce. 

1001 poster 

DETECTION OF PROSTATE CANCER RECURRENCE WITH 

11C-ACETATE PET AND PET/CT IN PATIENTS WITH EARLY BIO- 

CHEMICAL FAILURE AFTER PROSTATECTOMY 

I. Verbiene 1 , A. Bergman 2 , D. Kudrén 1 , J. Sörensen 2 , I. Turesson 1 

1 UPPSALA UNIVERSITY HOSPITAL, Oncology, Uppsala, Sweden 

2 UPPSALA UNIVERSITY HOSPITAL, Radiology, Uppsala, Sweden 

Purpose: Localisation of prostate cancer recurrence in patients with early 

biochemical failure after prostatectomy with conventional image techniques 

is often not possible. Treatment decisions are different for relapse in the 

prostate bed, pelvic lymph nodes and distant metastases. The main purpose 

of our study was to evaluate the diagnostic potential of 11C-Acetate Positron 

Emission Tomography (PET) combined with Computed Tomography (CT) in 

prostate cancer patients with early biochemical failure after prostatectomy in 

order to select adequate treatment modality: conventional radiotherapy (RT), 

Intensity Modulated Radiotherapy (IMRT) or hormonal treatment (HT). 

Materials: 63 patients with prostate specific antigen (PSA) relapse after 

prostatectomy were referred for radiotherapy to prostate bed and underwent 

11C-Acetate PET or PET/CT in 2003- 2007. Clinical data and PET/CT images 

were reviewed. 11C-Acetate uptake was interpreted as pathological, 

non pathological or equivocal. Standardised uptake value (SUV) > 2 was 

considered as pathological, and SUV < 2 as non pathological. 

Results: The first investigation of patients was done with PET in 11 patients 

and with PET/CT in 52 patients. PET and PET/CT showed pathological uptake 

in 43 (68%) cases (7 in the PET and 36 in the PET/CT group), and 

equivocal uptake in 3 (5%) cases. PSA ranged between 0.12 ng/ml and 4.3 

ng/ml (median 0.9 ng/ml). Pathological uptake in prostate bed was found in 

28 cases, in pelvic lymph nodes in 29 cases, and distant metastases were 

found in 6 cases. Local recurrence in prostate bed only was found in 13 

cases and in pelvic lymph nodes with or without uptake in prostate bed in 24 

cases. Pathological uptake in pelvic lymph nodes among the 29 patients was 

distributed as: il. externa, il. interna, il. communis region in 86%, 17%, and 

31% of cases respectively. After the first examination with PET or PET/CT, 

32 patients underwent RT to prostate bed, 5 patients were treated with IMRT 

to prostate bed and pelvic lymph nodes, 1 patient was treated with RT for 

metastasis in bone, and 10 patients received HT with bicalutamid. After observation 

and HT 19 patients underwent another PET/CT confirming earlier 

detected pathological uptake. After the second PET /CT examination additionally 

4 patients received RT to prostate bed, 7 patients were treated with 

IMRT to prostate bed and pelvic lymph nodes. 7 patients still are on HT only, 

and 6 patients did not receive any subsequent treatment. In follow-up, biochemical 

regression was found in 22 of 24 patients in RT group, and in 5 of 6 

patients in IMRT group. Totally 12 patients underwent a new PET/CT investigation 

after at least 3 month treatment with bicalutamid, and in 10 of those 

cases regression of pathological 11 C- Acetate uptake was observed. 

Conclusions: Our findings indicate that 11 C- Acetate PET/CT has the potential 

in selecting of treatment modality in prostate cancer patients with early 

biochemical recurrence. 

1002 poster 

DEVIATION CORRECTION METHOD FOR POSITIONING PATIENTS 

WITH PROSTATE ADENOCARCINOMA AND A HIP IMPLANT, BY 

MEANS OF IMPLANT MARKERS 

K. De Vos 1 , P. Swiggers 1 , J. Goossens 1 , I. Jacobs 1 , C. Goor 1 , D. Van 

den Weyngaert 1 

1 ZNA MIDDELHEIM, University Radiotherapy Antwerp, Antwerpen, Belgium 

Purpose: New techniques in radiation therapy for prostate cancer, like IMRT, 

allow to give higher doses to the target volume and improve outcome. This 

implicates that the daily set up error must be minimized. The use of implanted 

radio-opaque prostate markers in combination with daily verification of these 

markers by portal imaging (EPID) makes it possible. Standard, two EPI are 

taken before the treatment , at gantry angle 0 and 90, and compared with 

the resp. DRR at these angles. Correction can be made in L/R, S/I and 

A/P direction. A deviation of 3 mm is tolerated at our institution. In patients 

with prostate implant markers and a hip prosthesis, the markers can not be 

visualised on the lateral port image. Adjusting the lateral angle, the markers 

become visible but the measured deviation of the position of the markers 

does not correlate exactly with the actual deviation in the patient. Our goal 

was to find the proper gantry angle for visualisation of the prostate markers, 

calculate the actual deviation at the different gantry angles and make an easy 

to use chart for patient repositioning. 

Materials: The visualisation of the implant prostate markers was evaluated in 

a patient with a left hip prosthesis, using portal images at different gantry angles 

and comparing with the resp. DRR’s. The difference between measured 

deviation and the actual deviation was calculated for different gantry angles 

and deviations using a formula (Fig 1) These measurements are put into a 


S 319 

chart. 

Results: In case of a left hip prosthesis, the prostate markers were easy 

to visualise on portal images at a gantry angle of 60 ◦ . Calculation of the 

real, actual deviation according to the measured deviation, showed a minimal 

difference for measurements at the gantry angle of 60 ◦ . At an angle of 45 ◦ 

the measured distance is underestimated, so the tolerance level for correction 

of patient repositioning must be lower. If there is a deviation of 9 mm or more 

, patient repositioning must be calculated according to the easy to use chart 

(Table 1) 

Conclusions: Patients with a hip implant who need radiation for a prostate 

cancer can have a correct daily set up verification using prostate markers and 

EPI controls if the proper angle is chosen for the lateral portal image and a 

correction formula is used to calculate the actual deviation. One has to be 

aware that the tolerance level for patient repositioning has to be adapted at 

different gantry angles used for portal images. 

1003 poster 

DOES ADJUVANT HORMONAL THERAPY IMPROVE FREEDOM 

OF BIOCHEMICAL RECURRENCE IN PATIENTS WITH HIGH-RISK 

PROSTATE CANCER? 

H. Abusaris 1 , P. Hofman 1 , M. Vulpen, van 1 , J. Batterman 1 

1 UMC UTRECHT, Radiotherapy, Utrecht, Netherlands 

Purpose: The quality of the radiotherapy treatment has been significantly improved 

due to the introduction of sufficient position verification, a sufficiently 

high dose to the prostate and IMRT. Recently several groups showed that the


benefit of adjuvant hormonal therapy might be less than expected in current 

radiotherapy treatments. The aim of this retrospective study is to determine 

if adjuvant hormonal therapy has an effect on freedom of biochemical recurrence 

in patients only with high-risk prostate cancer. 

Materials: From 2001 till 2005 117 patients have been treated with IMRT up 

to 76 Gy in 35 fractions. Position verification was performed using fiducal 

gold markers. Tumors were staged as T3 > G2 (gleason 7 of higher) pN0/x 

M0/x. Mean PSA was 20 ng/ml (range 1.4 96 ng/ml). In this period there 

was no consensus in our region on the indications for adjuvant hormonal 

therapy. During this period 43 patients were treated with hormonal therapy. 

When comparing the groups with or without hormonal therapy there were no 

significant differences between these groups, except for a difference in PSA. 

The group with hormonal therapy had a mean PSA of 25.7 ng/ml (range 4.0 

96 ng/ml), and without hormonal therapy a mean PSA of 16.7 ng/ml (range 

1.4 68.0 ng/ml). 

Results: The median period of biochemical recurrence was 25 months 

(range 3 51 months). There was no significant difference in freedom of biochemical 

relapse between the patients who did or did not receive adjuvant 

hormonal therapy. Multivariate analysis showed only PSA and Gleason were 

predictors for biochemical recurrences. 

Conclusions: In our patient group adjuvant hormonal therapy does not appear 

to improve freedom of biochemical recurrence in patients with high-risk 

prostate cancer. 

1004 poster 

DOES THE SHAPE OF THE RECTAL SURFACE DOSE DISTRIBU- 

TION PREDICT THE RISK OF LATE RECTAL INCONTINENCE AND 

BLEEDING, IN PATIENTS TREATED WITH HIGH-DOSE 3DCRT FOR 

LOCALIZED PROSTATE CANCER? 

S. Gianolini 1 , L. Widesott 2 , T. Rancati 3 , E. De Martin 4 , C. Bianchi 5 , A. 

Monti 6 , L. Menegotti 7 , M. Pasquino 8 , M. Stasi 9 , G. Fellin 10 , V. Vavassori 

11 , R. Valdagni 3 , C. Fiorino 4 

1 TOMOTHERAPY EUROPEGMBH, Diegen, Belgium 

2 AGENZIA PROVINCIALE PROTONTERAPIA, Trento, Italy 

3 NATIONAL INSTITUTE OF CANCER, Prostate Program, Milano, Italy 

4 SAN RAFFAELE INSTITUTE, Medical Physics, Milano, Italy 

5 OSPEDALE DI CIRCOLO, Medical Physics, Varese, Italy 

6 OSPEDALE S. ANNA, Medical Physics, Ferrara, Italy 

7 OSPEDALE S. CHIARA, Medical Physics, Trento, Italy 

8 OSPEDALE DI IVREA, Medical Physics, Ivrea, Italy 

9 SCIENTIFIC INSTITUTE CANDIOLO, Medical Physics, Candiolo, Italy 

10 OSPEDALE S. CHIARA, Radiotherapy, Trento, Italy 

11 OSPEDALE DI CIRCOLO, Radiotherapy, Varese, Italy 

Purpose: Significant correlation between rectal DVHs and late toxicity was 

found in the AIRO-PROS0102 study: V70 and V75 were predictive of bleeding 

and V40 was predictive of incontinence. Further analysis of the dose 

distribution of the rectal surface (through dose maps) may add important refinements 

to dose-volume relationships for rectal toxicity. 

Materials: Data of more than 650 patients, prospectively scored by a questionnaire 

with a 3-year follow-up, were available; among these patients, it was 

decided to recover the treatment planning of the patients enrolled in five Institutions 

(n = 437). 3D planning data were exported to a dedicated software 

(Vodca) for dose maps calculation and analysis. Up to now, data of 301/437 

of 4/5 Institutions were processed and analysed. Dose map shapes of patients 

with toxicity were compared with 20 randomly chosen patients without 

toxicity. About bleeding, only patients treated to at least 78 Gy were considered 

(n =90, 11/90 bleeders). Incontinent patients were 9/301. A number 

of parameters were compared (see figure), such as maximum width and 

height of the 40, 70 and 75 Gy surface isodoses (S40, S70, S75) and the 

distances between S40, S70, S75 and the cranial/caudal limits of the rectum 

(TOP/BOTTOM). Height and TOP/BOTTOM distances were considered 

both in absolute (cm) and % value. Anterior and posterior rectal surface were 

considered separately (only for S40). 

Results: No difference between bleeders and no bleeders was evident for 

S70. S75 was higher (31% vs 26% p=0.21), in the bleeding group: S75 height 

was > or = 48 % in 7/11 vs 4/20 for bleeders and non-bleeders respectively 

(p=0.02). 6/11 bleeders showed a S75 TOP distance < or = 28% vs 6/20 

(p=0.18) for non bleeders (Fig. 1a). Concerning incontinence, a significantly 

larger S40 height was found in incontinent patients (95% vs 82%, p=0.008, 

ant-rectum; 75% vs 58%, p=0.05, post-rectum); significant lower values of 

S40 TOP distance (2% vs 13%, p=0.009, ant-rectum; 13% vs 29%, p=0.03, 

post-rectum) were also found for incontinent patients (Fig. 1b). 

Conclusions: The correlation between S75 height and bleeding confirms the 

predictivity of V75 for patients treated to > or = 78 Gy without any evidence of 

additional spatial effects; the trend found for S75 TOP should be confirmed in 

a larger population. Both height and S40 TOP are predictive of rectal incontinence, 

suggesting a stronger weight of the cranial portion of the rectum in 

the occurrence of this complication. 

1005 poster 

DOMINANT LOBE BOOST TO 84 GY USING 3D-CRT: ACUTE AND 

LATE TOXICITY REPORT 

A. Alvarez 1 , V. Macías Hernández 1 



Purpose: To investigate the feasibility and the potential increase of side effects 

when radiation dose is escalated focusing the therapy in the dominant 

lobe (DL). 

Materials: 19 selected intermediate-high risk patients (T2-3 N0 M0 and Gleason 

≥7) were irradiated between 10-2004 and 102005. A dominant lobe was 

defined when both DRE and TRUS biopsies were positive in the same lobe 

but negative in the contralateral lobe. 3 mm slices CT was realised in supine 

position, full bladder, empty rectum, immobilisation of feet. Initial CTV was 

prostate and seminal vesicles. Prescribed dose to PTVPSV (CTV + 7-12 

mm) was 78-80 Gy in 2 Gy/fraction. Prescribed dose to PTVDL (dominant 

lobe + 5 mm) was 4-6 Gy in 2 Gy/fraction. Pelvic lymph node areas were 

irradiated in 6 patients (31.6%) to a dose of 45-46 Gy. 3DCRT was delivered 

with 6 isocentric fields (box technique in the pelvis irradiation). Minimum 

PTV dose was 95% of prescribed dose. RTOG was assessed prospectively 

according RTOG scale. 

Results: Age 68.5 ± 5.9 y.o. Mean follow-up is 34.6 ± 3.9 months. DL 

volume was 13 ± 5.9 cc. Mean dose to PTVPSV and PTVDL were 81.8 ± 

0.8 Gy and 83.7 ± 0.6 Gy. Hormonal therapy was associated to RT in 94.7% 

patients (30 months in 84.2% and 6 months in 10.5%). Mean rectal dose 

was 44.9 ± 6.5 Gy. Maximum acute urinary toxicity was 8 G0 (42.1%), 7 

G1 (36.8%), 4 G2 (21%). Acute intestinal toxicity was 15 G0 (51.7%), 4 G1 

(21%), 0 G2 (0%). Any patient had acute G3 toxicity. Late toxicity is shown in 

figures 1 and 2. Up to now there are no biochemical/clinical failures.

Conclusions: Dose escalation with boost on DL to 84 Gy using 3D-CRT 

technique is feasible. Early results show acceptable rates of acute and late 

toxicity. 

1006 poster 

DOSE DISTRIBUTION IN 3-DIMENSIONAL CONFORMAL RADIO- 

THERAPY FOR PROSTATE CANCER: COMPARISON OF FEMUR 

DOSES FOR FOUR TREATMENT TECHNIQUES 

D. Karacetin 1 , A. Cakýr 2 , F. Agaoglu 2 , H. Camlýca 2 , A. Ergen 2 , Y. Dizdar 

2 , E. Darendeliler 2 

1 

SISLI ETFAL RESEARCH AND TRAINING HOSPITAL, Radiation Oncology, 


2 

ISTANBUL UNIVERSITY, Radiation Oncology, Istanbul, Turkey 

Purpose: Conformal radiotherapy of the prostate is an increasingly common 

technique . When using 3-D conformal radiotherapy methods, it is desirable 

to protect the vital organs such as, bladder, rectum and femur. In this study, 

our aim was, to compare the results of femur doses with co-planar beam 

arrangement from a variety of four-field (4F), five-field (5F), six-field (6F) and 

seven-field (7F) plans a dose escalated conformal radiotherapy schedule. 

Materials: At Istanbul Universtity, Medical Facuty of Radiation Oncology 

Clinic,between January 2005 - December 2006, In total 22 patients, with 

Prostate carcinoma, had been CT scanned ( 0.50 mm ) in supine position. 

During this CT scanning using, Sim Pro (CMD USA) programme, PTV 

CTV, bladder, rectum, femur volumes were entered and dose-volume histogrammes 

were created. The prostate plus seminal vesicles , formed CTV 

1 and only prostate was defined to be CTV 2. During the formation of PTV, 

into CTV; I, from the anterior-superior-inferior 8 mm, and from posterior 5 

mm tolerance were taken into account. After ,volume determination is calculated, 

using XIO (CMS-USA) 3-D Treatment Planning Computer each patient 

,4F (45 degrees -25%, 135 degrees -25%, 225 degrees 25%, 315 degrees 

-25%) , 5F( 0 ◦ -% 20, 45 ◦ -% 20, 90 ◦ -%20, 270 ◦ -%20, 315 ◦ -%20), 

6F( 45 ◦ -%20, 90 ◦ -%10, 135 ◦ -%20, 315 ◦ -%20, 270 ◦ -%10, 225 ◦ -% 20) 

and 7F ( 0 ◦ -%4, 45 ◦ -%12.9, 90 ◦ -%22.2, 135 ◦ -%12.9, 315 ◦ -%12.9, 270 ◦ - 

%22.2, 225 ◦ -%12.9) was entered. 7380 cGy, was calculated to be given to 

prostate. With the use of Siemens Oncor 18 MV photons conformal radiotherapy 

was applied. In DVH analysis, following were observed ; PTV 95%, 


S 321 

PTVmin, PTVmax, PTVmed., CTV%95, CTVmin, CTVmax, CTVmed, rectum 

%25,40,60,70; bladder %25,40,60,70 and left femur and right femur doses . 

Results: Our statistical evaulation was made using SPSS method and we 

found femur doses following; 4F V50 1030 cGy (min 58- max 1390) , 5F V50 

2425 cGy ( min. 540 max.3631), 6F V50 1769 cGy (min. 1234 max. 3912), 

and 7F V50 3230 cGy (min. 2150 max. 4137) When paired samples T test 

was made, we found considerebal lower femur doses for 4F techniques ( p ; 

0,05 ). 

Conclusions: We reached to the conclusion that, during radiotherapy of 

Prostate carcinoma especially the doses received by rectum, is the determinig 

factor, in view of late-toxicitity. During the usage of lateral fields (90 

degrees 270 degrees) to protect the rectum, the doses received by femur 

heads was observed to be increasing. Especially with older pateints, the critical 

doses of 52 Gy for TD5/5, 65Gy for TD 50/5 were obsreved to be reached 

late toxicity for 4F,5F,6F and 7F. 

1007 poster 

DOSE-VOLUME CHARACTERISTICS AND ACUTE TOXICTY OF 

HYPOFRACTIONATED INTENSITY-MODULATED ARC THERAPY 

(IMAT) + ANDROGEN DEPRIVATION (AD) AS PRIMARY THERAPY 

FOR LYMPH NODE METASTASIZED PROSTATE CANCER. 

W. De Neve 1 , V. Fonteyne 1 , G. Villeirs 2 , C. De Wagter 1 , F. Jacobs 1 , K. 

Vandecasteele 1 , P. Ost 1 , G. De Meerleer 1 



Purpose: To report on the dose distribution and acute upper and lower 

gastro-intestinal (GI) and genito-urinary (GU) toxicity of IMAT + AD for lymph 

node metastasized prostate cancer. 

Materials: 25 patients with T1-4 N1 M0 prostate cancer were treated with 

IMAT and 3 years of AD as primary treatment. The clinical target volume 

(CTV) was the prostate and seminal vesicles. The elective lymph node areas 

(lnn) were delineated as CTV_lnn. The planning target volume (PTV) 

and PTV_lnn were created using a 3-dimensional expansion of the CTV and 

CTV_lnn of 7mm. Rectum, sigmoid colon, bladder, small bowel and femoral 

heads were delineated as organs at risk. In view of the low α/β of prostate 

cancer, a median dose of 69.3 Gy and 50 Gy was prescribed in 25 fractions to 

the CTV and CTV_lnn respectively. There was a hard constraint on minimal 

dose for CTV_lnn and PTV_lnn i.e. 48 Gy and 46 Gy respectively. Toxicity 

was scored weekly during treatment and 1 and 3 months thereafter. Upper 

and lower GI toxicity were scored using the RTOG toxicity scoring system and 

RILIT (1) respectively. GU toxicity was scored based on a combined RTOG- 

SOMA/LENT-CTC toxicity scoring system. 

Results: The median follow-up time was 3 months. The median age was 

63 years (range 53-75 year). The median PSA was 14.4 ng/ml (range 2.7- 

126 ng/ml). N1 disease was confirmed histologically in 21 patients (pN1, 

lymphadenectomy) and based only on imaging (CT-MRI) in 4 patients. The 

mean prescription dose (± SEM) to the CTV and PTV was 70 Gy (± 0.2 Gy) 

and 69 Gy (± 0.2 Gy) respectively. For an α/β=3, this corresponds with a 

normalized isoeffective dose calculated for fractions of 2 Gy (NID2) of 81.2 

and 79.5 Gy respectively. The minimal dose on the CTV_Lnn and PTV_Lnn 

was 48.6 Gy (± 0.3 Gy) and 45.9 Gy (± 0.3 Gy) corresponding to a NID2 of 

49 and 46 Gy respectively (α/β=3). The mean and maximal rectal dose was 

52 Gy (± 0.8 Gy) and 68 Gy (± 0.2 Gy) respectively. The mean and maximal 

sigmoidal dose was 32 Gy (± 2.1 Gy) and 62 Gy (± 0.8 Gy) respectively. The 

mean and maximal small-intestine dose was 3 Gy (± 1.3 Gy) and 55 Gy (± 

2.3 Gy) respectively. The mean and maximal bladder dose was 47 Gy (± 

1.4 Gy) and 70 Gy (± 2.8 Gy) respectively. No acute grade 4 toxicity was 

reported. No patient developed upper GI or grade 3 lower GI toxicity. The 

incidence of lower GI and GU toxicity is represented in table 1 

Conclusions: Hypofractionated IMAT as primary therapy for lymph node 

metastasized prostate cancer is technically feasible. Compared to the RTOG- 

9413 data (2) the toxicity reported in our series is low and comparable to the 

more recentely published data of pelvic irradiation with intensity-modulated 

radiotherapy (3). References: 1. Fonteyne V. et al. Radiot Oncol. 2007; 

84: 156-163. Late radiotherapy-induced lower intestinal toxicity (RILIT) of 

intnsity-modulated radiotherapy for prostate cancer: the need for adapting 

toxicity scales and the appearance of the sigmoid colon as co-responsible 

organ for the lower intsetinal toxicity. 2. Roach M. et al. Int J radiat Oncol Biol 

Phys. 2006; 66: 647-653. Whole-pelvis, "mini-pelvis," or prostate-only external 

beam radiotherapy after neo-adjuvant and concurernt hormonal therapy in 

patients treated in the radiation therapy oncology group 9413 trial . 3. Muren 

LP et al. 2008; doi:10.1016/j.ijrobp.2007.11.060. Intensity-modulated radiotherapy 

forr pelvic lymph nodes in locally advanced prostate cancer: planning 

procedures and early experiences.


1008 poster 

DOSE-VOLUME RELATIONSHIP FOR ACUTE BOWEL TOXICITY 

FOR PATIENTS TREATED FOR PROSTATE CANCER INCLUDING 

PELVIC NODES IRRADIATION 

C. Fiorino 1 , F. Alongi 2 , L. Perna 1 , S. Broggi 1 , G. M. Cattaneo 1 , C. 

Cozzarini 2 , N. Di Muzio 2 , F. Fazio 2 , R. Calandrino 1 

1 SAN RAFFAELE INSTITUTE, Medical Physics, Milano, Italy 

2 SAN RAFFAELE INSTITUTE, Radiotherapy, Milano, Italy 

Purpose: Finding dose-volume relationships between dose-volume histograms 

(DVHs) of the intestinal cavity (IC) and grade 2-3 RTOG/EORTC 

acute bowel toxicity (tox) 

Materials: In the period Jan04 Nov07 pelvic nodes were irradiated in 191 patients 

with localized prostate cancer treated with radical or adjuvant/salvage 

intent. Planning and clinical data, including tox and a number of clinical information, 

were fully available for 175/191 and current analysis refers to this 

group. 91/175 were treated with a conventional 4-fields technique (50.4 Gy, 

1.8 Gy/fr) while the remaining 84 were treated with IMRT using conventional 

Linac (n = 26, 50.4 Gy, 1.8 Gy/fr) or Helical Tomotherapy (n=58, 50-54 Gy, 

1.8-2 Gy/fr, with simultaneous delivery of 65.8-72 Gy in 28-32 fractions). For 

all patients, IC outside the PTV was contoured and the DVH of the first 6 

weeks of treatment (i.e.: referred to pelvis irradiation) was recovered. The 

correlation between a number of clinical variables (hormonal therapy, age, diabetes, 

hypertension, abdominal/pelvic surgery prior to radiotherapy (SURG), 

prostatectomy), DVH parameters (from V10 to V55) and tox was investigated 

by uni- (UVA) and multivariate (MVA) analyses. 

Results: 22/175 G2-G3 tox were registered (no-IMRT:19/91; IMRT: 3/84). 

UVA analyses (Cox model and Mann-Withney U test) showed that DVH of 

IC is highly correlated with tox (from V20 to V50); p-values ranged between 

0.001 and 0.0002 with higher predictivity for V40-V50. Among the clinical variables, 

only previous prostatectomy (p=0.066) or SURG (p=012) were slightly 

correlated with tox. In a MVA (Cox model) including V45 (corresponding to 

the minimum p-value in UVA), SURG and prostatectomy, the most predictive 

parameters were V45 (p=0.002) and SURG (p=0.05, HR=2.4). When only 

considering the no-IMRT patients, a significant correlation of V10-V50 was 

found, with highest predictivity for V10 (p=0.001), clearly due to the enhancing 

effect of the correlation between V10-V20 and the treated volume in a box 

technique scenario. 

Conclusions: Owing to the concomitant delivery of conventional and IMRT 

techniques, it was possible to quantitatively assess the large volume effect 

of IC. Based on our findings, the risk of tox may be reduced to few % when 

using the following dose-volume constraints for IC (outside PTV): V30 < 300 

cc, V40 < 150 cc, V50 < 35 cc. Previous abdominal surgery seems to be an 

independent predictor of acute bowel toxicity. 

1009 poster 

DOSIMETRIC ANALYSIS OF REAL TIME AND POST IMPLANTATION 

DOSIMETRY FOR PROSTATE 

M. Smith 1 , S. Stathakis 2 , A. Gutierrez 1 , G. Swanson 1 , M. Joyner 1 , N. 

Papanikolaou 1 

1 UTHSCSA, Radiological Sciences, San Antonio, USA 

2 UTHSCSA, Department of Radiological Sciences, San Antonio, USA 

Purpose: To quantify the changes in prostate volume pre and post 

brachytherapy and its effect on the dose to the volume using volume studies 

of low dose radiation seed implants for prostate cancer. 

Materials: The most common method for prostate seed implants utilizes a 

pre implant ultrasound for planning and a post implant CT scan for verification. 

Ultrasound images of the patients in the lithotomy position were obtained 

one to two weeks before the implant procedure. The ultrasound has better 

resolution than the CT, but the source position is better delineated on CT 

scan. On the pre-planning ultrasound, the prostate and the urethra were contoured 

and then an optimized treatment plan was developed using the Spot 

pro 3.1 software. This was done in order to obtain the number of Palladium- 

103 seeds needed to be ordered to deliver the prescribed dose of 120Gy to 

the target. On the day of the implant a new optimized plan was created using 

real-time ultrasound images with the patient in actual treatment position with 

the resulting actual shape and volume of the prostate. Linked seeds were 

implanted according to the latter plan. A CT scan was performed after the 

seeds were implanted and the prostate and urethra were contoured. The 

post-implant treatment plan was developed by locating the seeds on the CT 

images and calculating the dose distribution. 

Results: The volumes of the planning and real time ultrasounds were similar. 

By comparing the pre and the post implant prostate volumes of five patients, 

it was found that there was an increase in volume by 31% to 39%. The 

magnitude of volume change correlates with the relative size of the prostate. 

In every case the post implant CT plan did not receive 100% of the dose as 

planned. The amount of deficit is correlated to the volume change. According 

to the post implant plans the V100 ranged from 81% to 99%. The smaller 

prostate volumes showed the lower values of V100. The tables and graphs 

of patients 1, 2, and 3 are shown below. 

Conclusions: Prostate volume changes due swelling after the implant appears 

to be associated with a reduction in dose coverage between the pre 

and post plans. It appears that these factors effect treatment planning which 

can ultimately determine the success in treating the cancer. 

1010 poster 

DOSIMETRIC INTERCOMPARISON BETWEEN INTENSITY MODU- 

LATED RADIATION THERAPY (IMRT) AND HIGH DOSE RATE (HDR) 

BRACHYTHERAPY TO DETERMINE WHICH TECHNIQUE OFFERS 

A HIGHER SELECTIVITY TO THE PROSTATE 

J. Hermesse 1 , S. Biver 1 , B. Thissen 1 , B. Warlimont 1 , N. Jansen 1 , P. 

Coucke 1 , P. Nickers 2 

1 

CHU LIEGE (LIEGE UNIVERSITY HOSPITAL), Radiation Oncology, Liege, 

Belgium 

2 


Purpose: We aimed at comparing the dose distribution of HDR brachytherapy 

and IMRT in prostate cancer. 

Materials: The tomodensitometric data of ten successive patients treated 

with HDR brachytherapy for prostate cancer were recovered for the dosimetric 

intercomparison. The Nomos-CorvusR treatment planning system (TPS) was 

used for IMRT planning while dose distribution for HDR brachytherapy was 

calculated with the BrachyvisionR TPS. A theorical dose of 10 Gy applied by 

2 Gy per fraction (EQD2) was prescribed on the PTV in the IMRT approach. 

We selected an α/β ratio of 1.5 Gy to calculate a biological equivalent unique 

dose for HDR brachytherapy (5.22 Gy). The dose was normalized in order to 

allow 95% coverage of the PTV. The dose-volume histograms were calculated 

for PTV and organs at risk (OAR’s). For these, doses were converted to 

EQD2, considering an α/β ratio of 3 Gy. Differences between the obtained 

dose-distributions were compared with a two-sided Student’s t-test. 

Results: Dose heterogeneity is more pronounced with HDR brachytherapy 

with a mean dose to the PTV of 23.8 Gy as compared to 10.5 Gy with IMRT. 

Cold spots are similar with both methods: 7.93 Gy and 8.17 Gy respectively 

with IMRT and HDR brachytherapy (p=0.6). The rectal dose is reduced by 

HDR brachytherapy as 0.5cc of the rectum received 5.9 Gy as compared

to 10.2 Gy with IMRT (p


Conclusions: The RS and LKB models manage to capture actual selfassessed 

rectal toxicity in the 64-78 Gy region. Future work includes analysis 

of the full patient data set, inclusion of fractionation effects, confidence estimates, 

validation of predictive power of the models and inclusion of organ 

motion in the analysis. 

1015 poster 

EUD BASED IMRT FOR PROSTATE CANCER IN 174 PATIENTS - 

TOXICITIES AND CORRELATING DOSE-VOLUME-HISTOGRAMS 

U. Ganswindt 1 , G. Nguyen 1 , A. Horst 2 , B. Frey 2 , M. Söhn 2 , M. Alber 2 , 

M. Bamberg 1 , C. Belka 1 

1 UNIVERSITY OF TUEBINGEN, Dept. of Radiooncology, Tuebingen, Germany 

2 UNIVERSITY OF TUEBINGEN, Dept. of Radiooncology, Biomedical Physics, 


Purpose: Intensity modulated radiotherapy (IMRT) is widely used for definitive 

radiotherapy of prostate cancer. IMRT allows the application of escalated 

radiation doses without increased side effects, in particular, gastrointestinal 

toxicity (GI). However, the planning procedures, the dose calculation 

algorithms and methods of clinical application vary between the individual institutions. 

From 2002 on IMRT planning in our department was based on 

Hyperion R○ (University of Tuebingen) software package. As a unique feature 

dose prescription is based on the Equivalent Uniform Dose (’EUD’) concept 

and DVH optimisation relies on biological modes. In addition all dose are 

calculated using the VMC Monte Carlo algorithm for dose calculation. Aim 

of our work was to retrospectively determine early and late toxicities in 174 

patients treated with IMRT in the primary setting. Potential co-morbidities and 

dose-volume-histogram(DVH)-data are analysed multivariately. 

Materials: All patients treated from 2002 until May 2007 were evaluated. 

Early side effects ([GI], genitourinary [GU]) were recorded using the RTOG 

criteria. Late toxicities were recorded with a clinical examination and a 

standardised questionnaire (RTOG-, CTC-, LENTSOMA-criteria). Multivariate 

analysis included the side effects, DVH- and EUD-data and relevant comorbidities. 

Results: 174 patients were included into the analysis. 84 patients (high-risk 

profile) received treatment of the prostate (70 Gy) with pelvic lymph nodes 

(50.4 Gy). 90 patients received a radiation dose of 70-74 Gy to the prostate 

alone, among them 15 patients with focal dose escalation (71-78 Gy). The 

mean dose to the prostate (without focal dose escalation) was 71.1 Gy. Early 

toxicities GU (RTOG): Grade 0: 10.1%, Grade 1: 45.6%, Grade 2 (along 

RTOG definition any use of drugs): 42.6%, Grade 3: 1.8%, Grade 4: 0%. 

Early toxicities GI (RTOG): Grade 0: 8.3%, Grade 1: 37.5%, Grade 2: 53.0%, 

Grade 3: 1.2%, Grade 4: 0%. The evaluation of late toxicities and the correlation 

with the EUD-/DVH-data is not completed yet and will be presented at 

the meeting. 

Conclusions: In regard to the high proportion of patients with additional radiation 

treatment of the pelvic lymph nodes the early toxicity rates were low 

with 1.8% (GU) and 1.2% (GI) Grade 3 side effects, and no grade 4 side effect 

(RTOG), respectively. The final analysis should enable for an EUD based 

prediction of toxicities. 

1016 poster 

GOLD SEEDS TRACKED IMAGE-GUIDED HYPOFRACTIONATED 

PROSTATE RADIOTHERAPY: IS INTRAPROSTATIC SEEDS MIGRA- 

TION A CONSISTENT PITFALL? 

F. Munoz Hernandez 1 , P. Franco 1 , A. Guarneri 1 , P. Ciammella 1 , C. Iftode 

1 , G. Cattari 1 , C. Fiandra 1 , R. Ragona 1 , U. Ricardi 1 

1 OSPEDALE SAN GIOVANNI BATTISTA-UNIVERSITY OF TURIN, Radio- 

threrapy, Turin, Italy 

Purpose: The better biochemical relapse-free survival compared with standard 

dose radiation therapy (RT) in prostate cancer has been permitted by 

the use of highly conformal dose escalation RT fields achieving a better target 

coverage with a concomitant sparing of organs at risk (OARs). Potential 

pitfalls of patient consist in setup errors and organ motion. In order to reduce 

these geometrical uncertainties, target localization and image-guided 

techniques (IGRT) might be usefull. Implanted fiducial markers (GMs) are an 

efficient and accurate tracking method for prostate IGRT as they are thought 

as surrogates for prostate position. Therefore, the positional stability of these 

markers is crucial. Aim of this study is to assess the impact of gold seeds 

migration on the correct localization of the prostate gland, within a hypofractionated 

prostate RT protocol currently ongoing at our institution. 

Materials: Ten patients have been enrolled hitherto onto this protocol, consisting 

in the administration of a radiation nominal dose of 70,2 Gy in 26 

daily fractions (fx) of 2,7 Gy each [(EQD2): 84.4 Gy with an α/atio of 1.5 

Gy], delivered over 5 weeks. 3 cylindrical gold markers were implanted under 

ultrasound-guidance at least one week before RT. After implantation, 

treatment planning Computed Tomography (CT) and Magnetic Resonance 

(MR) imaging were performed, in supine position, using a knee-feet immobilisation 

device. CT-MR imaging co-registration was performed, using a 

bony landmarks matching methods. All volumes including OaRs and CTV 

were contoured on MR-images. The Clinical Target Volume (CTV) included 

the prostate and proximal seminal vesicles. Each seed was identified and 

contoured separately. For each patient, pelvic CT scans were acquired in 

the treatment position to track seeds position within the prostate, during the 

course of RT. We assumed that a modification of inter-marker distance might 

be a reliable indicator of seeds migration. The positions of GMs were obtained 

on a CT/MR data set and 3 space coordinates (x, y, z) were considered 

for measurements. 23 CT scans were analysed; t-student analysis was performed 

comparing the difference of inter-seeds distance between reference 

CT scans, and CT during RT. 

Results: Results regarding seeds movement: Table 1. 

Conclusions: Our results suggest that GMs used as intra-prostatic markers 

may actually maintain their relative positions within the gland over the entire 

course of RT. Hence, they may be a reliable fiducial marker to correct patients’ 

position according to the estimated organ motion. Gold seeds can be considered 

a valid and safe surrogate of prostate gland position in the localization 

process. 

1017 poster 

HDR BRACHYTHERAPY OF PROSTATE CANCER AS A BOOST 

AFTER EXTERNAL BEAM RADIOTHERAPY 

M. Kanikowski 1 , J. Skowronek 1 , M. Kubaszewska 1 , A. Chichel 1 


Purpose: External beam radiotherapy (EBRT) in prostate cancer treatment 

seems to be nowdays as effective as surgery procedure. Low dose rate 

brachytherapy (LDR-BT) can be applied as a single modality treatment in 

patients from low risk group with localized tumors. High dose rate brachytherapy 

(HDR-BT) is very usefull in increasing prostate dose after EBRT (boost) 

which shortens whole radiation treatment. There is no clear recommendations 

about doses and schemes of combined radiation treatment (EBRT-BT). 

The aim of this work was to analyze the results and complications of two 

schemes in treatment of patients with initially localized prostate cancer. 

Materials: One group (I) consisted of 30 patients with prostate cancer were 

treated with interstitial HDR brachytherapy since June 2006 till January 2007 

in Greatpoland Cancer Center. HDR-BT was performed with a remote afterloading 

microSelectron unit (192Ir source) one months after 50 Gy’s dose 

of external beam radiation therapy. After brachytherapy planning (Nucletron 

SWIFT system has been applyed), all patients recieved 15 Gy’s of HDR-BT 

dose in one fraction The age of patients ranged from 59 to 80 years, avarage 

70.3 years. They were divided in risk groups by TNM, initially PSA, and Gleason 

score datas. The low, intermediate and high risk groups consisted of 

11 (36,7%), 11 (36,7%) and 8 (26,7%) men, respectively. The mean lavel of 

iPSA was settled on 36,4 ng/ml ranged from 0,06 till 594 ng/ml. The most of 

patients (21-70%) belonged to T2 group. In the same time we have treated 

a group (II) of 17 men in other scheme (46 Gy EBRT + 2 x 10 Gy HDR BT). 

Mean age of patients was 68,6 (range 58-76 years). Risk groups consisted 

as follows (low 58,8% , intermediate 17,6%, high 23,5%). The mean lavel 

of iPSA observed was 16,9 ng/ml (range 0,12-50 ng/ml). 20 of all patients 

(42,6%) recieved EBRT alone, 27 (57,4%) EBRT combined with hormonal 

therapy, before HDR-BT application (group I+II). Maximum androgen blocade 

had 16 of them (34,04%) and 11 patients (23,4%) recieved LHRH analogs or 

antyandrogen treatment only. In 6 of men ( 12,76%) has been treated after 

transrectal resection procedure (TURP). Number of needles used in HDR-BT 

treatment in the first group was 13,7 in mean value (ranged 8 - 18), in the 

second group 15,25 (ranged 9-18) . Tolerance of the treatment and acute 

complications in two groups were discussed. 

Results: Median observation time was 21 months. None of patients enrolled 

to our study died during this time. Complete remission was observed in 25 

patients (83,3%) from I group and in 10 (58,8%) from II group. Locoregional 

progression was noted in 2 patients (6,67%) and in 1 patient (5,89%) from 

group I, II respectively. 1 patient from group I developed distant metastases. 

Urologic and gastrointenstinal side effects were noted in most of patients from 

both groups. Dysuria 40 and 29,4%, incontinance 0 and 5,88%, frequency 

50 and 41,1%, rectal bleeding 20 and 5,88% from I and II groups respectively. 

Conclusions: 1. HDR brachytherapy of prostate cancer can be used as a 

boost after or before external beam radiation therapy in different treatment 

schemes. 2. Small groups comparison shows better results in group with 

higher dose of HDR-BT but less complication rate in two fractions group. 3. 

To confirm superiority of each kind of modality treatment a comperative investigation 

two larger groups is needed.

1018 poster 

HEALTH-RELATED QUALITY OF LIFE AFTER 76 GY INTENSITY- 

MODULATED RADIOTHERAPY FOR LOCALIZED PROSTATE 

CANCER: A PROSPECTIVE AND LONGITUDINAL STUDY 

V. Marchand 1 , S. Bourdin 1 , C. Charbonnel 2 , E. Rio 1 , C. Munos 3 , L. 

Campion 2 , M. A. Mahe 1 , S. Supiot 1 

1 

CENTRE RENÉ GAUDUCHEAU, Radiotherapy, Saint-Herblain, France 

2 

CENTRE RENÉ GAUDUCHEAU, Department of Biostatistics, Saint-Herblain, 

France 

3 

CENTRE RENÉ GAUDUCHEAU, Radiophysics, Saint-Herblain, France 

Purpose: To study longitudinal quality of life after 76 Gy intensity-modulated 

radiotherapy (IMRT) in patients with localized prostate carcinoma. 

Materials: From February to December 2006, fifty-five patients with localized 

prostate cancer were treated with IMRT and daily repositioning with the Exac- 

Trac system to a total dose of 76 Gy with a Novalis linear accelerator. Quality 

of life (QoL) was measured by the European Organization for Research and 

Treatment of Cancer core questionnaire (EORTC QLQ-C30 version 3.0), and 

the prostate specific EORTC QLQ-PR25, before radiotherapy (baseline) and 

at 2, 6, 18 months after treatment. QoL changes in time were considered 

clinically relevant if >10 points, and statistically significant if p values < 0.01 

using the Wilcoxon signed ranks test. 

Results: Median age was 73 [54-80]. Patient distribution for cancer risk according 

to D’Amico’s classification was: 18.0% low risk, 60.2% intermediate 

risk, 21.8% high risk. 45.5% patients received androgen deprivation therapy 

(ADT) for a median time of 6 months. QoL at 2 months showed significant deterioration 

in fatigue (+11.31, p = 1.10-7), urinary symptoms (+9.07, p = 3.10- 

11), dyspnea (+7.27, p = 0.008), emotional functioning (-7.02, p = 0.002), 

social functioning (-6.36, p = 0.003), cognitive functioning (-4.85, p = 0.004) 

and role functioning (-3.39, p = 0.007). QoL at 6 months showed improvement 

for all parameters except in fatigue (+5.86, p = 0.003) and urinary symptoms 

(+5.86, p = 0.0004). QoL at 18 months is being assessed and updated data 

will be presented. 

Conclusions: High-dose IMRT and accurate position verification allow to 

preserve a good QoL despite a temporary deterioration at 2 months. Subsequent 

more mature data at 18 months will be necessary to confirm our 

results. 

1019 poster 

HELICAL TOMOTHERAPY FOR LOCALIZED PROSTATE CARCI- 

NOMA: HOW MUCH IMRT DO WE REALLY NEED? 

O. De Hertogh 1 , Y. Boukour 2 , N. Christian 3 , P. Castadot 3 

1 C.H. PELTZER - LA TOURELLE, Radiotherapy, Verviers, Belgium 

2 C.H. PELTZER - LA TOURELLE, Medical Physics, Verviers, Belgium 

3 UNIVERSITÉ CATHOLIQUE DE LOUVAIN, ST-LUC UNIVERSITY HOSPITAL, 

Molecular Imaging and Experimental Radiotherapy, Brussels, Belgium 

Purpose: External-beam radiation therapy (EBRT) is indicated for patients 

presenting with localized prostate carcinoma (LPC). Compared to conventional 

3D-EBRT, intensity-modulated radiation therapy (IMRT) helps reduce 

the dose to the neighbouring organs-at-risk (OAR). In some radiotherapy departments, 

not all linear accelerators are equipped for IMRT: choosing which 

patients receive 3D-EBRT instead of IMRT may become a concern. Delivering 

part of the treatment with IMRT, and part with 3D-EBRT, may both reduce 

the dose to the OAR and increase the number of patients having access to 

IMRT. 

Materials: Comparative planning was performed to assess the dose to 

the rectum and bladder when delivering 3D-EBRT, IMRT using helical TomoTherapy, 

or a combination of both (CMRT, combined modality radiation 

therapy). Twenty plans were retrospectively performed for patients presenting 

with LPClocalized prostate carcinoma (cT1c-T2cN0M0, Gleason score 

6, PSA


1021 poster 

HIGH DOSE RATE BRACHYTHEAPY OF LARGE VOLUME 

PROSTATE - A SUITABLE ALTERNATIVE 

A. Korba 1 , S. M. Shah 1 , A. Razek 1 , J. Frazier 1 , P. Gilson 2 , P. Siami 2 , B. 

Romick 2 , B. Samm 2 , T. Gadient 2 , D. Foertsch 2 , M. Zenni 2 , T. Renschler 

2 , A. Sorensen 1 , W. Fisher 2 

1 

EVANSVILLE CANCER CENTER/TRI-STATE PROSTATE CANCER CENTER, 

Evansville, Indiana, USA 

2 

TRI-STATE PROSTATE CANCER CENTER, Evansville, Indiana, USA 

Purpose: LDR brachytherapy in large volume prostates may not provide adequate 

dose coverage of the prostate gland. There is also an inherent risk 

of urethral and rectal morbidity due to the need of placing a relatively greater 

number of seeds in order to approach a dose/volume appropriate to the enlarged 

glands. HDR brachytherapy is a suitable alternative for treating cancer 

of the prostate with volume of 50 cc or more. Since January 2001 we have 

adopted High Dose Rate brachytherapy for the treatment of prostate cancer 

in order to improve optimization of dose to prostate and limit doses to rectum 

and urethra. Our experience has shown that this technique is quite effective 

in treating prostates of volumes greater than 50 cc. 

Materials: A total of 576 patients with early prostate cancer stage T1,2N0 

were treated with a protocol of combined EBRT and HDR brachytherapy as 

of December 2007. EBRT was delivered using 3D conformal radiotherapy or 

IMRT with a tumor dose of 45-50.4 Gy. EBRT was followed after a period 

of 4 weeks by two fractions of TRUS guided HDR brachytherapy two weeks 

apart as an outpatient procedure. Each fraction was designed to deliver 10 

Gy to the prostate gland with 0-2 mm margin with 12 Gy to be delivered to 

the peripheral zone. The dose to rectum and urethra was limited as not to 

exceed 10 and 12 Gy respectively. Dose optimization was achieved using CT 

image based ABACUS algorithm. 

Results: One hundred two of the patients had prostate volume of greater than 

50 cc as determined by pre-implant ultrasound volume study and ranged from 

50 to 110 cc. Fifty-six patients had prostate volume greater than 60 cc with 

six patients having volume greater than 100 cc. In only one case adequate 

coverage was not provided due to pelvic anatomical limitations and EBRT 

was increased as a substitute. No severe, acute morbidity was noted within 

this group of patients. 

Conclusions: Our experience demonstrates that large volume prostates can 

be effectively treated using HDR brachytherapy. This procedure is tolerated 

very well with minimal side effects. Long term observation will be required to 

observe late complications and biochemical control. 

1022 poster 

HIGH DOSE TOMOTHERAPY TREATMENT OF LYMPH NODAL 

RELAPSE IN PROSTATE CANCER 

G. Berardi 1 , F. Alongi 1 , C. Cozzarini 1 , C. Landoni 2 , M. Picchio 2 , C. 

Fiorino 3 , G. Guazzoni 4 , C. Messa 2 , F. Fazio 5 , N. Di Muzio 1 

1 ISTITUTO SCIENTIFICO SAN RAFFAELE, Radiation Oncology, Milan, Italy 

2 ISTITUTO SCIENTIFICO SAN RAFFAELE, Nuclear Medicine, Milan, Italy 

3 ISTITUTO SCIENTIFICO SAN RAFFAELE, Physics, Milan, Italy 

4 ISTITUTO SCIENTIFICO SAN RAFFAELE, Urology, Milan, Italy 

5 ISTITUTO SCIENTIFICO SAN RAFFAELE / IBFM-CNR, Radiation Oncology 

/ Nuclear Medicine, Milan, Italy 

Purpose: Management of prostate cancer patients with biochemical relapse 

after radical prostatectomy (RP) or radiotherapy (RT) is controversial. 

[(11)C]Choline-PET/CT is an accurate diagnostic tool for the detection of 

lymph-node metastases of recurrent prostate cancer. Both pelvic radiotherapy(PRT) 

and pelvic +/-retroperitoneal lymph-node dissection have been tried 

to improved outcome in such patients, but it is unclear the optimal choice for 

ultimate nodal control. The objective of our study is the feasibility of high conformal 

intensity modulated treatment with helical Tomotherapy (HTT) in lymph 

nodal metastases(LNM) detected on [ (11)C]Choline- PET/CT. 

Materials: From January 2005 to September 2007, 14 patients(pts) with biochemical 

recurrence (median PSA:2.56), based on evidence of lymph-node 

metastases on [(11)C]choline-PET/CT scan were treated with high dose moderate 

hypofractionated HTT. The median age is 67 years (64-77). Pts were 

previously underwent RP (7 ) or RT (7): 2 radical, 5 post-operative salvage/adjuvant. 

Gleason score was always >6. All pts have a minimum follow 

up longer than 3 months. In 10/14 and 3/14 [(11)C]choline-PET/CT detected 

para-aortic and pelvic LNM respectively. Only 1/14 presented an extra 

abdominal LNM. The treatment plan was based on [(11)C]choline-PET/CT 

study. In all pts the detected LNM received higher dose thank to the technique 

of simultaneous integrated boost allowed by HTT. The doses ranging 

from 42Gy in 6 fraction to 67.2 in 28 fractions. However 9/14 were treated in 

25-28 fractions with doses from 57.5 to 67,2 Gy. All patients received previously 

hormonal deprivation and 4/14 also estramustine and/or taxotere. 

Results: The treatment was well tolerate. Only 2 pts experimented upper 

gastrointestinal G1 acute toxicity. No pts showed late toxicity. All pts were 

studied with [(11)C]Choline- PET/CT both for staging/ treatment planning, before 

RT and in 12/14 pts 40-120 days after the end of HTT. 8/14 presented 

Complete Response, 2/14 had Partial Response> 50%. 3 pts showed stable 

disease in irradiated area but progression in other sites. One patients died 

for tumour progression. The median follow-up for the entire group was 12 

months (4-24). 13/14 pts documented a significant reduction of PSA value 

after HTT without mild-.high grade of acute or late toxicity. 

Conclusions: Our data show that high dose moderate hypofractionated 

HTT[(11)C]Choline- PET/CT guided is safely and efficacy . The good rate 

of local control registered, suggest that high dose radiotherapy could be a 

valid treatment in prostate pts with lymph nodal relapse. Obviously we need 

a longer follow-up and more patients for definitive conclusion. 

1023 poster 

HIGH-DOSE IMRT FOR PROSTATE CANCER WITHOUT CLINICALLY 

RELEVANT DETERIORATION IN LONG-TERM QUALITY OF LIFE 

I. Lips 1 , U. van der Heide 1 , A. Boeken Kruger 2 , C. van Gils 3 , M. van 

Vulpen 1 


2 UMC UTRECHT, Urology, Utrecht, Netherlands 

3 UMC UTRECHT, Julius Center for Health Sciences and Primary Care, 

Utrecht, Netherlands 

Purpose: High-dose radiotherapy for prostate cancer demonstrates improved 

biochemical relapse-free treatment outcomes. However, an increased radiation 

dose causes a higher risk of developing complications and therefore a 

decrease in quality of life (QoL) could be expected. In a prospective study we 

investigated the long-term QoL after high-dose radiotherapy for prostate cancer 

with intensity-modulated radiotherapy (IMRT) and fiducial marker-based 

position verification. 

Materials: Between October 2003 and November 2004 95 patients with 

prostate cancer were treated with 76 Gy IMRT using gold fiducial markerbased 

position verification. Late rectal and bladder toxicity usually occurs 

within 3 years of completion of radiotherapy and therefore we measured QoL 

before treatment (baseline) and 1 month and 3 years after treatment. Patients 

completed the following questionnaires: RAND-36, EORTC QLQ-C30 

and EORTC QLQ-PR25 to measure the general, cancer specific and prostate 

cancer specific QoL, respectively. Differences in QoL before and after treatment 

were tested with a Wilcoxon signed ranks test. A p-value of < 0.01 was 

considered as statistically significant. QoL changes in time of 10 points or 

more were considered clinically relevant. 

Results: Figure 1 shows the QoL scores at baseline and after 3 years for all 

items (9 out of 29) with a significant change in QoL over time. After 3 years 

the QoL score concerning physical functioning, cognitive functioning, bowel 

symptoms/functioning and sexual activity deteriorated significantly, however 

only sexual activity demonstrated a change in QoL of more than 10 points. 

Comparing the long-term sexual activity scores with the measurements 1 

month after treatment did not demonstrate a significant decrease in QoL, thus 

sexual activity deteriorated directly after radiotherapy treatment and remained 

stable further on.The following QoL items showed a significant improvement 

between baseline and 3 years: social functioning, mental health, change in 

health, insomnia and emotional functioning. The QoL difference in time of 

change in health was the only clinically relevant improvement. The "response 

shift" mechanism (referring to a changed internal standard on which patients 

base their perception, due to a life-threatening disease) may be involved in 

this improvement over time. 

Conclusions: High-dose radiotherapy reduces long-term QoL in terms of 

sexual activity, while all other QoL items demonstrated no decrease in QoL 

3 years after treatment and even showed a small improvement in QoL over 

time. Therefore IMRT and accurate position verification provide the possibility 

to deliver high-dose radiotherapy without clinically relevant deterioration in 

long-term QoL.

1024 poster 

HIGH-DOSE-RATE BRACHYTHERAPY (HDR-BT) COMBINED WITH 

EXTERNAL BEAM RADIATION THERAPY (EBRT) IN PATIENTS WITH 


T. Inomata 1 , T. Shimbo 1 , M. Takahashi 1 , Y. Uesugi 1 , H. Azuma 2 , Y. 

Katsuoka 2 

1 OSAKA MEDICAL COLLEGE, Radiology, Osaka, Japan 

2 OSAKA MEDICAL COLLEGE, Urology, Osaka, Japan 

Purpose: To determine the effects of high dose rate brachytherapy (HDR-BT) 

combined with external beam radiation therapy (EBRT), and to evaluate the 

early and late sequelae. 

Materials: From April 2002 to September 2007, 73 patients with prostate 

cancer were treated with HDR-BT combined with EBRT. The patients were 

stratified into three groups: low-risk [19 patients (pts.)](GS: 2-6 and PSA==20 or T3). In all patients, EBRT 

was performed before HDR-BT. According to the risk groups, the dose ranging 

from 40 Gy / 20 fractions / 4 weeks to 50.4 Gy / 28 fractions / 5.6 weeks 

was delivered to the patients. After the completion of EBRT, HDR-BT was 

performed with 19.5 Gy / 3 fractions / 2 days. 

Results: The median follow-up was 30 months. Biochemical failure according 

to the Phoenix definition (nadir + 2 ng/ml) was 0 (0 %), 1 (5.3 %), and 

4 (11.4 %) in the low-, intermediate- and high-risk groups, respectively. The 

overall survival rate was 97.5 % and the cause-specific survival rate was 100 

%. Early sequelae were evaluated according to the Common Toxicity Criteria 

(CTC)-ver3.0. Early genitourinary toxicity of grade 1, grade 2, and grade 

3 was observed in eight, two and one patient, respectively. All the patients 

recovered from early toxicity within 12 months. Only one patient who had 

previously undertaken TURP suffered from urinary tract stricture (late toxicity), 

and that patient had urinary tract dilatation. There was no early and late 

rectal damage. 

Conclusions: HDR-BT combined with EBRT is especially applicable to 

intermediate- and high-risk group patients in addition to low-risk group patients 

with prostate cancer. Biochemical failure and early and late sequelae 

were acceptable. In particular, HDR-BT had the advantage of avoiding rectal 

toxicity. 

1025 poster 

HYBRID I-125 PROSTATE BRACHYTHERAPY TECHNIQUE: IM- 

PROVED DOSIMETRY AND 2-YEAR POTENCY 

J. Nobes 1 , M. Cunningham 1 , S. Khaksar 1 , S. Langley 1 , R. Laing 1 



Purpose: Erectile dysfunction following prostate brachytherapy is reported to 

be related to dose received by the penile bulb. To minimise this, whilst preserving 

prostate dosimetry, we have developed a technique for I-125 seed 

brachytherapy using both stranded seeds and loose seeds delivered with 

a Mick applicator, and implanted via the sagittal plane on trans-rectal ultrasound. 

Materials: Post-implant dosimetry and potency rates were compared in 120 

potent patients. In Group 1, 60 patients were treated using a conventional 

technique of seeds implanted in a modified-uniform distribution. From January 

2005 a novel, hybrid technique was developed using stranded seeds 

peripherally and centrally-distributed loose seeds implanted via a Mick applicator 

(Group 2). The latter technique allows greater flexibility when implanting 

the seeds at the apex. Each patient was prescribed a minimum peripheral 

dose of 145Gy. No patients received external beam radiotherapy or hormone 

treatment. There was no significant difference in age or pre-implant potency 

score (mean IIEF-5 score 22.4 vs. 22.6, p=0.074) between the two groups. 

Results: The new technique delivers lower penile bulb doses (D25 as %mPD 

Group 1: 61.2 ± 35.7, Group 2: 29.7 ± 16.0, p


1028 poster 

HYPOFRACTIONATED EXTERNAL BEAM RADIOTHERAPY FOR 

ORGAN-CONFINED PROSTATE CARCINOMA DELIVERED WITH 

THREE DIFFERENT IMAGE-GUIDED METHODS: PRELIMINARY 

RESULTS IN 105 CONSECUTIVE PATIENTS. 

B. A. Jereczek-Fossa 1 , D. Zerini 2 , F. Serafini 2 , E. Petazzi 2 , C. Fodor 2 , R. 

Cambria 3 , C. Garibaldi 3 , F. Cattani 3 , A. Vavassori 2 , G. B. Ivaldi 2 , V. D. 

Matei 4 , B. Rocco 4 , G. Musi 4 , F. Verweij 4 , E. Scardino 4 , O. de Cobelli 5 , 

P. Fossati 2 , R. Orecchia 1 

1 

EUROPEAN INSTITUTE OF ONCOLOGY -STATE UNIVERSITY, Radiotherapy, 

Milan, Italy 

2 

EUROPEAN INSTITUTE OF ONCOLOGY, Radiotherapy, Milan, Italy 

3 

EUROPEAN INSTITUTE OF ONCOLOGY, Medical Physics, Milan, Italy 

4 

EUROPEAN INSTITUTE OF ONCOLOGY, Urology, Milan, Italy 

5 

EUROPEAN INSTITUTE OF ONCOLOGY -STATE UNIVERSITY, Urology, Milan, 

Italy 

Purpose: To assess the feasibility and toxicity of the hypofractionated imageguided 

radiotherapy (IGRT) for localized prostate cancer, using three different 

devices implemented at our Institute: transabdominal ultrasound prostate 

localization (BATTM-NOMOS), ExacTracTM (X-Ray 6D system - BrainLAB), 

megavoltage Cone-Beam CT (On Board Imager CTTM - Varian Medical System). 

Materials: From August 2006 to February 2008, 104 pts (mean age 71 yrs) 

with localized prostate cancer (T1a-T2c), mean GS 6.3, mean iPSA 9.04 

ng/ml, were treated with an hypofractionated schedule (2.7 Gy/fr. x 26 fr., 

up to 70.2 Gy, equivalent to 84.2 Gy, with an a/b ratio of 1.5 Gy). According 

to NCCN 2007 definition, 48 pts were classified as low risk, 42 pts as intermediate 

risk and 15 pts as high risk. 34 pts. had some form of hormonal 

treatment. Pts were asked to have full bladder and empty rectum and were 

treated in supine position. The CTV to PTV margins were 7 mm in all directions, 

except 3 mm posteriorly. The CTV was the prostate only for 56 pts. 

and prostate plus the seminal vesicles for 49 pts. Daily target localization 

was performed before each radiotherapy session: 72 pts underwent prostate 

localization with BATTM, 18 pts with Cone-Beam CT and 15 pts had Exac- 

TracTM X-Ray assisted positioning (based on the visualisation of the gold 

markers VisicoilTM introduced in the prostate before simulation). Pts. were 

evaluated at the end of the treatment and at 3 and 6 months thereafter. The 

RTOG/EORTC criteria were used to classify side effects. 

Results: All the pts. have completed the radiotherapy course (mean total 

treatment time 39.7 days): acute toxicity resulted as follows: acute genitourinary 

G0 21 pts., G1 41 pts, G2 36 pts and G3 only 7 pts. Acute rectal toxicity 

G0 58 pts, G1 34 pts, G2 11 pts and G3 2 pts. After a median follow-up of 7.2 

mts. late toxicity was recorded in 52 pts and resulted for rectal symptom: G0 

47 pts and G1 5 pts. Genitourinary toxicity was: G0 27 pts., G1 17 pts., G2 6 

pts. and G3 2 pts. No biochemical failure was observed with a marked reduction 

of PSA from a mean iPSA of 9.04 ng/ml to 1.79 ng/ml at 3 months and to 

1.4 ng/ml at six months. IGRT with BATTM was faster than with the other two 

technique, with a median time for the procedure of 2.9 min, but the accuracy 

was operator-dependent and influenced by patient anatomy, prostate position 

and dimension and probe pressure. Cone-Beam CT and X-Ray assisted 

positioning showed less bias but have higher cost, are time-consuming, add 

X-ray exposure and the necessity of invasive markers insertion procedure (for 

ExacTracTM). 

Conclusions: The three IGRT technique applied are feasible procedures that 

allow for high precision irradiation and for the reduction of the normal tissue 

exposure. Acute toxicity profile of the hypofractionated schedule employed is 

good but longer follow-up is warranted in order to evaluate late toxicity and 

tumor outcome data. 

1029 poster 

HYPOFRACTIONATION VERSUS STANDARD FRACTION IN 

PROSTATE CANCER: ANALYSIS OF THE ACUTE TOXICITY. 

B. M. Saracino 1 , M. G. Petrongari 1 , S. Gomellini 1 , S. Arcangeli 1 , V. 

Landoni 2 , S. Marzi 2 , L. Strigari 2 , I. Sperduti 3 , G. Arcangeli 1 

1 

IRE, Radiotherapy, Rome, Italy 

2 

IRE, Physics, Rome, Italy 

3 

IRE, Department of Statistics, Rome, Italy 

Purpose: The aim of this study is to evaluate the tolerance and the acute 

toxicity of a hypofractionation in comparison to a conventional fractionation 

regimen in the radiotherapy of prostate cancer. 


proven, high risk prostate cancer were recruited to this study. All 

patients received a total androgen deprivation (AD) for 9 months. After 2 

months of AD, all patients underwent a 3D conformal radiotherapy to the 

prostate and seminal vesicles. Patients were randomized to receive a conventional 

fractionation of 80 Gy in 40 fractions in 8 weeks, or 62 Gy in 20 fractions 

in 5 weeks, (4 fractions per week). Acute hematological, gastrointestinal 

(GI) and genitourinary (GU) toxicities were weekly evaluated according to the 

RTOG/EORTC score system. 

Results: No patient experienced acute hematological toxicity or grade 3 gas- 

trointestinal (GI) or genitourinary (GU) toxicity. The acute grade 2 GI and 

GU toxicities were observed in the 23 % and 38% of patients, respectively, 

in the control arm and in 40% and 42%, of patients, respectively, in the hypofractionation 

arm (p=0.0007 for GI and 0.052 for GU toxicity). The actuarial 

analysis showed an earlier appearence of both toxicities in the hypofractionation 

arm in comparison to the standard arm. However, when both toxicities 

were analyzed as a function of the normalized total dose in 2 Gy fraction 

equivalents (NTD2) using α/β value of 10 for acute reactions, the statistical 

significance disappeared for both toxicities, suggesting that the acute toxicity 

is simply anticipated in the hypofractionation with respect to conventional 

fractionation. This observation was confirmed by the evaluation of the Mucositis 

Index which did not result in a significant difference between the 2 

arms, analyzed either as a function of time or of NTD2. 

Conclusions: These preliminary results suggest that the hypofractionation 

schedule is well tolerated although the acute G2 toxicity in this group, was 

observed earlier than in conventional fractionation. 

1030 poster 

I-125 PROSTATE BRACHYTHERAPY: A COMPARISON OF PRE- 

PLANNED VERSUS INTRA-OPERATIVE PLANNING METHODS 

M. Cunningham, J. Nobes 1 , S. Voulgaris 1 , S. Khaksar 1 , S. Langley 1 , R. 

Laing 1 



Purpose: Controversy exists regarding the value of real-time intra operative 

planning over a more conventional two-stage technique in prostate 

brachytherapy (BXT). As an experienced centre in BXT having performed 

over 1200 implants, we set to compare the post implant dosimetry of patients 

treated by either a real-time technique compare to a two-stage approach. 

Materials: The post-implant dosimetry for 60 patients treated with I- 

125 prostate BXT at our centre was analysed. Group 1 consists of 30 

consecutively-treated patients, whose implant was performed as a conventional 

two-stage procedure. Patients attended for a volume study, which was 

then planned and implemented at least 2 weeks later. From January 2007, 

25% of cases were treated with an intra-operatively planned implant; we have 

analysed the results of the last 30 consecutively-treated of these patients as 

Group 2. This technique involved a volume study and planning prior to the implant 

date, as in Group 1. At the time of the implant, intra-operative dosimetry 

was calculated after insertion of the peripheral stranded seeds. This information 

was used to determine the number and position of central loose seeds 

required, which were delivered via the Mick applicator. Following implantation 

of these loose seeds, dosimetry was re-acquired, and further seeds added if 

necessary to optimise coverage. The first five cases treated in this manner 

were excluded from the analysis, to account for the potential learning curve. 

For both groups, CT-based dosimetry occurred at Day 1 post-implant. 

Results: Prostate volume was not significantly different in each group (mean 

38.3cc ±10.7 vs. 35.4 ± 11.2, p=0.31). The number of seeds implanted also 

did not differ (82.9 ± 14.4 vs. 76.9 ± 15.2, p=0.12), although there was a 

trend to a lower number of seeds used when compared to the planned number 

in Group 2 (78.4 ±13.1 vs. 76.9 ± 15.2, p=0.65). Prostate implant quality 

and dosimetric coverage did not significantly differ between the two methods, 

as shown by the mean V100 (92.8% ± 5.4 vs. 91.1% ± 4.4, p=0.18) and 

D90 as %mPD (109% ± 12.4 vs. 104% ± 8.6, p=0.06) although there was 

a trend to slightly lower D90 in Group 2. The prostate V150 (52.7% ± 14.3 

vs. 43.6% ±9.3, p=0.01) and urethral V150 (6.49% ±11.1 vs. 1.68% ± 3.8, 

p=0.03) were lower in Group 2, although both mean values are within tolerance. 

Mean urethral dose (135Gy ± 21.4 vs. 126Gy ± 23.5, p=0.11) and 

rectal V100 (1.07cc ± 0.7 vs. 0.89cc ± 0.5, p=0.29) were unaffected. 

Conclusions: In experienced centres with an existing high standard of implant 

quality, it may be difficult to improve dosimetric outcome. The incorporation 

of intra-operative planning into the implant procedure did not impact on 

the quality of prostate dosimetry, although there is evidence for a beneficial 

effect upon urethral dose and prostate V150. Further studies will examine 

whether this translates into clinical benefit. 

1031 poster 

IMAGE-GUIDED IMRT REDUCING URETHRAL DOSE FOR 

PROSTATE CANCER -AN EVALUATION OF ACUTE AND LATE 

ADVERSE EFFECTS- 

K. Narazaki 1 , Y. Takai 1 , M. Mitusuya 1 , Y. Ogawa 1 , H. Ariga 1 , K. Takeda 

1 1 1 1 1 1 

, M. Koto , T. Sakayauchi , K. Fujimoto , K. Jingu , E. Nakata , S. 

Yamada 1 

1 

TOHOKU UNIVERSITY SCHOOL OF MEDICINE, Radiation Oncology, Sendai, 

Japan 

Purpose: We have treated clinically localized prostate cancer patients by 

image-guided IMRT using fiducial markers in the prostate and image-guided 

devices, with dose reduction to the peri-urethral area by 5 % of prescribed 

dose of 80Gy/40fr by dose painting. The purpose is to report our results 

of adverse effect to gastrointestinal (GI) and genitourinary (GU) tract, of the

image-guided IMRT reducing urethral dose for prostate cancer. 

Materials: Between January 2004 and May 2007, 74 patients with clinically 

localized prostate cancer were treated with image-guided IMRT with dose 

reduction to peri- urethral area. These patients consist of 4 patients with low 

risk, 11 intermediate risk and 59 high risk. 

Results: Median follow-up time is 12.4 months. A patient has died of intercurrent 

disease so far. The 3-year PSA relapse-free survival rates for 

patients in low, intermediate and high risk groups according to the ASTRO 

definition were 100%, 100% and 94.0%,respectively. No grade 2-4 late GU 

tract complications have been observed so far. The incidence of grade 2 late 

GI complications was 2.6%, and no grade 3-4 late complications have been 

observed. 

Conclusions: Our outcomes have been excellent so far.No late adverse effects 

of GU tract have been observed by image-guided IMRT reducing urethral 

dose. 

1032 poster 

IMPACT OF INTER-FRACTIONAL CHANGES IN RECTUM AND 

BLADDER ON PROSTATE RADIOTHERAPY 

S. Gonzales 1 , D. Lim Joon 1 , V. Khoo 2 , R. Height 1 , A. Mercuri 1 , J. 

McNamara 1 , M. Lawlor 1 , A. Viotto 1 , M. Bell 1 , W. Fernando 1 


2 ROYAL MARSDEN, Radiotherapy, London, United Kingdom 

Purpose: Dose escalation for prostate cancer RT has shown to improve patient 

outcomes. However, there is a need to constrain dose to the adjacent 

organs at risk to avoid increasing toxicity. These structures, specifically the 

bladder and rectum, are constantly subjected to inter-fractional movement 

that is not currently accounted for in planning methods. Potential volumetric 

and spatial changes may lead to differences between delivered dose, and 

dose predicted by the RT plan. This study aims to asses volume and spatial 

changes of rectum and bladder over the treatment course and to investigate 

the potential impact on dosimetry. 

Materials: The study population consisted of 5 patients with high-risk locally 

advanced prostate cancer. Median age of 68, mean PSA 9.1 ug/L, median 

Gleason score of 8. The patients were instructed to follow strict bladder and 

bowel preparation prior to simulation and treatment. They underwent simulation 

with CT and co-registered MRI following prostate gold fiducial seed 

insertion. All patients were planned to recieve 78 Gy in 39 fractions using 

IMRT. CT scans were performed at weeks 2, 4 and 6 of treatment and coregistered 

with the initial planning CT using gold seed matching. The rectal 

and bladder walls were contoured on each of the CT scans and the absolute 

bladder and rectal volumes were assessed. Spatial changes were analysed 

using a bounding box technique. Bladder and rectum DVH parameters were 

collated and analysed for each of the CT scans. 

Results: Analysis indicated the volume of the rectum increased over the 

course of treatment by a mean of 11.84cm 3 (range 5.22 to 27.72). The bladder 

volume reduced with subsequent fractions by a mean of 14cm 3 (range 

9.32 to 14.08). The predominant direction of shift for the wall of the rectum 

was anterior, at a mean shift of 0.37cm (range 0.02 to 0.73). The bladder 

moved in the anterior and superior directions at a mean shift of 0.46cm (range 

0.24 to 0.6), and 0.22cm (range 0.07 to 0.3) respectively. The rectum V40 and 

V50 increased by a mean of 2.71% (range 1.06 to 5.37) and 2.77% (range 

1.21 to 5.26%) respectively. The bladder DVH showed a mean decrease in 

the V50 and V70 by 1.63% (range -3.7 to 0.67) and 1.53% (range -3.38 to 

1.11) respectively. 

Conclusions: Rectum and bladder volumes demonstrated some interfractional 

variability. The rectum shifted towards the high dose gradient, 

hence an increase in dose to the organ. The bladder shifted away from the 

high dose region, resulting in a reduction in dose. There were only small 

changes in spatial relationships, perhaps reflecting our strict bowel and bladder 

preparation. Consequently, the dosimetry was predominantly within the 

planned constraint values, and estimated dose delivered to the rectum and 

bladder was within acceptable toxicity levels. A larger patient cohort will provide 

more definitive conclusions. 

1033 poster 

INFLUENCE OF SUPINE VERSUS PRONE PATIENT POSITION 

AND BLADDER FILLING ON DOSE TO ORGANS AT RISK IN 

RADIOTHERAPY FOR HIGH RISK PROSTATE CANCER 

K. Czigner 1 , P. Agoston 2 , G. Forgacs 1 , E. Pap 1 , Z. Zaka 1 , J. Fodor 1 


2 NATIONAL INSTITUTE OF ONCOLOGY, Budapest, Hungary 

Purpose: To compare dose volume parameters for organs at risk (OARs) at 

two different patient positions and different bladder filling in conformal pelvic 

irradiation for prostate cancer. 

Materials: Prospective evaluation of treatment plans of 14 patients receiving 

conformal locoregional radiotherapy for high risk prostate cancer was performed. 

CT scans of pelvis at 5-mm intervals were obtained for planning 

in four different ways. Two CT series were done with knee and ankle sup- 


S 329 

port (KAS) in supine position and with belly board (BB) in prone position 

with full bladder (FB). The series were repeated after patients have emptied 

their bladder (EB). According to patient position and bladder filling four different 

treatment plans (KAS-FB; BB-FB; KAS-EB; BB-EB) were generated on 

Philips-Pinnacle v7.6 planning system. Four-field technique (0 ◦ , 180 ◦ , 90 ◦ , 

and 270 ◦ ) was used for both pelvic and prostate irradiation. Planning treatment 

volumes (PTV) and OARs (i.e. rectum, rectum wall, bladder, bladder 

wall, bowels, sigmoid, femoral heads and penile bulb) were defined and delineated 

using identical definitions for the four patient setups. Similar relative 

weights of fields were applied for all patients to avoid dose volume differences 

due to weighting. Patient received 44Gy to the pelvis, 60Gy to prostate and 

vesicles and 78Gy to prostate with 2Gy daily fractions. It was required that at 

least 95% of volume of the PTV receive ≥95% of the prescribed dose. Dosevolume 

histograms were calculated for all PTVs and OARs. Vbladder50, 

Vbladder70, Vrectum50, Vrectum70, Vbowels50, Vbowels30, Vsigmoid50, 

Vsigmoid30 (%) data were compared with respect to patient setup and bladder 

filling. 

Results: Relative volumes of bladder (Vbladder50) were 48.7%, 48.1%, 

76.2% and 70.7% (p


1035 poster 

INTENSITY-MODULATED RADIOTHERAPY (IMRT) AS PRIMARY 

THERAPY FOR PROSTATE CANCER: AN UPDATE ON 5 YEARS 

BIOCHEMICAL CONTROL AND LATE TOXICITY. 

G. De Meerleer 1 , V. Fonteyne 1 , G. Villeirs 2 , W. De Neve 1 



Purpose: To give an update on biochemical non-evidence (bNED) and late 

toxicity after IMRT for prostate cancer. 

Materials: Between December 1998 and June 2005 133 patients were 

treated with IMRT as primary therapy for prostate cancer T1-4 N0 M0 at GUH. 

Table 1 shows the tumour characteristics. The clinical target volume (CTV) 

was the prostate +/- seminal vesicles (1). The planning target volume (PTV) 

was created to compensate for organ motion and set-up errors (2). First, patients 

were treated to a maximum rectum dose of 72 Gy (R72, n=51). Over 

time, patients were treated to a maximum rectum dose of 74 Gy (R74; n=82). 

Median CTV dose was 76 and 78 Gy for R72 and R74 respectively. The median 

PTV dose was 75 Gy and 77 Gy respectively, given in 36 or 37 fractions. 

Patients were divided into three risk groups to determine the use of androgen 

deprivation (AD). Thirty-four patients refused AD. Biochemical relapse was 

defined according to the Phoenix definition (3). To evaluate toxicity, patients 

were seen every three months during the first year after IMRT, 6-monthly upto 

5 years and yearly thereafter. Gastro-intestinal (GI) toxicity and genito-urinary 

(GU) toxicity was scored using an in-house developed scorings system RILIT 

(4) and the RTOG scoring system respectively. 

Results: The median follow-up time was 54 months. The overall 5-year bNED 

was 81%. A statistically significant difference (p

prognostic group. If AAD was already initiated before referral to our department, 

the MRI spectroscopy was not carried out. Image guidance was done 

using 18 Mv ultrasound for daily prostate positioning. To register acute gastrointestinal 

(GI) and genito-urinary (GU) toxicity, patients were seen weekly during 

treatment and 1 and 3 months thereafter. Toxicity was scored using the 

RTOG toxicity scale supplemented by an in-house developed scoring system 

adding 3 extra GI: (urgency, incontinence, rectal blood loss) and 1 extra GU 

symptom (incontinence) (2). 

Results: The median dose to the CTV and PTV was 80 and 78 Gy respectively. 

An IPL was found in 118 patients: 114 IPLM and 52 IPLS. The median 

dose to the IPLM and IPLS was 81 and 82 Gy, respectively. The inclusion 

of a IPL to perform a SIB did not change rectal or bladder DVH. There was 

no grade 3 and 4 acute GI toxicity. Grade 2 acute GI toxicity was present 

in 26 patients (11%). Three months after IMRT, all GI symptoms recovered, 

except urgency and incontinence. Grade 3 GU toxicity was present in 15 patients 

during treatment (7%), but was rarely observed 3 months thereafter. 

Ninety-five patients developed grade 2 acute GU toxicity (41%). There was 

no significant increase in grade 2/3 acute GI or GU toxicity when a SIB on the 

IPL was performed. 

Conclusions: Treatment-induced acute toxicity remains low when IMRT to 80 

Gy as primary therapy for PCa is used. A SIB on the IPL does not increase 

acute toxicity. References: 1. Diaz et al. Indications for and the significance 

of seminal vesicle irradiation during 3D conformal radiotherapy for localies 

prostate cancer. Int J Radiat Oncol Biol Phys 1994; 30: 323-329. 2. De 

Meerleer et al. Intensity-modaulted radiotherapy as primary treatment for 

prostate cancer: acute toxicity in 114 patients. Int J Radiat Oncol Biol Phys 

2004; 60: 777-787. 

1037 poster 

INTERSTITIAL HIGH DOSE RATE (HDR) BRACHYTHERAPY AS 

MONOTHERAPY FOR EARLY STAGE PROSTATE CANCER : A 


T. Neumann 1 , R. Mark 1 , P. Anderson 1 , M. Nair 1 , D. White 1 , S. Gurley 1 , 

R. Akins 2 




prostate cancer using Low Dose Rate (LDR) and High Dose Rate (HDR) 

technique has been reported with results comparing favorably to surgery and 

External Beam Radiation Therapy (EBRT). Often, HDR and LDR interstitial 

implant is combined with EBRT. There is little published data on HDR alone. 

We report our results with HDR alone. 

Materials: Between 1997 and 2008, 248 patients with T1 and T2 localized 

prostate underwent TRUS guided interstitial implant, under spinal anesthetic 

or local anesthetic. There were no Gleason Score or PSA exclusions. No 

patient received EBRT or Hormonal Blockade. Median Gleason Score was 

7 (range : 4 to 10). Median PSA was 9.3 (2.7 to 39.8). Treatment volumes 

ranged from 41 cm3 to 196 cm3. Treatment volume included the prostate and 

seminal vesicles in all cases. Radiation Treatment planning was performed 

using CT Scanning and the Nucletron Plato Treatment Planning System. Our 

IRB protocol for HDR alone, has called for two HDR Implants, spaced 4 weeks 

apart. The treatment volume received 2,250 cGy in 3 fractions prescribed to 

the 100% Isodose line, given over 24 hours. A 2nd implant was performed 

4 weeks later, delivering a further 2,250 cGy in 3 fractions, bringing the final 

dose to the prostate to 4,500 cGy in 6 fractions. Urethral dose points (12-16) 

were followed, and limited to < 105% of the prescription dose. 

Results: With a median follow-up of 88 months (range : 6 months to 144 

months), overall PSA Disease Free Survival (DFS) was 89.9% (223/248). 

By risk group, PSA DFS was 95.3% (61/64) for low risk, 90.6% (145/160) 

for intermediate risk, and 70.8% (17/24) for high risk disease. Acute and 

chronic complications were uncommon. Urethral stricture requiring dilatation 

has developed in 6.0% (15/248) of patients. Urinary stress incontinence has 

occurred in 3.6% (9/248). RTOG late bladder toxicities were : 0% Grade 4, 

0% Grade 3, and 3.6% (9/248) Grade 2. RTOG late rectal toxicities were : 

0.4% (1/248) Grade 4, 0% Grade 3, 1.2% (3/248) Grade 2, and 1.6% (4/248) 

Grade 1. 

Conclusions: With a median follow-up of 88 months, results with HDR implant 

alone compare favorably to EBRT, LDR +/- EBRT, and HDR + EBRT, 

both with regard to PSA DFS, and complications. HDR offers other advantages 

over LDR, such as no radiation exposure to hospital personnel, no 

seed migration, greater dose flexibility and precision of radiation dose delivery. 

Larger volumes can be treated with HDR. By omitting EBRT, bladder and 

rectal complications, and cost, appear to be significantly reduced. 

1038 poster 

INTERSTITIAL HIGH DOSE RATE (HDR) BRACHYTHERAPY UNDER 

LOCAL ANESTHESIA FOR EARLY STAGE PROSTATE CANCER : A 


S 331 


D. White 1 , R. Mark 1 , P. Anderson 1 , T. Neumann 1 , M. Nair 1 , S. Gurley 1 , 

R. Akins 2 




prostate cancer using Low Dose Rate (LDR) and High Dose Rate (HDR) 

techniques has been reported with results comparing very favorably to external 

beam radiation therapy. TRUS interstitial implant of the prostate has 

been traditionally performed under general or spinal anesthetic in an operating 

room. We report our results with a technique performed under local 

anesthesia in a Department procedure room. 

Materials: Patients with T1 and T2 localized prostate cancer were judged 

to be candidates for TRUS guided interstitial implant. Conscious sedation 

consisted of intravenous Morphine (12-22 mg) and Versed (6-14 mg), 

or intravenous Demerol (50-175 mg) and Versed (3-12 mg). Local anesthetic 

was given with a mixture of 1% Lidocaine, 0.25% Marcaine, 1:100,000 

Epinephrine, and 4% Sodium Bicarbonate neutralizing solution (20-120 cc). 

Local anesthesia was given to a 5 x 5 cm perineal area to a depth of 10 cm 

under TRUS guidance. The implants were placed under mobile multi-plane 

prostate template (Radiation Therapy Products Prostate Template) guidance 

using from 3 to 4 planes, and 12 to 22 needles. Needle spacing was 1.0 cm. 

The implant procedure included sigmoidoscopy and cystoscopy. 

Results: Between 2002 and 2008, 415 TRUS guided prostate implants were 

performed under local anesthesia. Median implant time was 45 minutes 

(range : 30 to 150 minutes). HDR treatment was given using the Nucletron 

afterloading system. The implant volume received 2,250 cGy in 3 fractions 

prescribed to the 100% Isodose line, given over 24 hours. Urethral dose 

points (12-16) were followed, and limited to < 105% of the prescription dose. 

The procedure was well tolerated, with all patients having completed the procedure. 

Three patients developed respiratory suppression, and required reversal 

with Narcan. All recovered uneventfully. Otherwise, there have been 

no acute complications to date. 

Conclusions: TRUS interstitial implant of the prostate under local anesthesia 

is feasible. Implant time, complications, cost, and scheduling convenience, 

compare favorably to general or spinal anesthetic technique. 

1039 poster 

INTRAOPERATIVE RADIOTHERAPY FOR LOCALLY ADVANCED 

PROSTATE CANCER: THE EXPERIENCE OF THE EUROPEAN 

INSTITUTE OF ONCOLOGY 

A. Vavassori 1 , M. Ciocca 2 , B. A. Jereczek-Fossa 3 , D. Zerini 1 , G. Ivaldi 1 , 

L. De Cicco 1 , R. Lazzari 1 , C. Fodor 1 , F. Cattani 2 , R. Cambria 2 , E. Rondi 

2 2 4 5 5 5 

, C. Garibaldi , O. de Cobelli , V. Matei , E. Scardino , F. Verweij , G. 

Musi 5 , B. Rocco 5 , A. Guido 1 , G. Gatto 1 , R. Orecchia 3 

1 


2 


3 

UNIVERSITY OF MILAN AND EUROPEAN INSTITUTE OF ONCOLOGY, 

Radiotherapy, Milan, Italy 

4 

UNIVERSITY OF MILAN AND EUROPEAN INSTITUTE OF ONCOLOGY, 

Urology, Milan, Italy 

5 


Purpose: To present the technique adopted for intraoperative radiotherapy 

(IORT) for locally advanced prostate cancer. 

Materials: Between June 2005 and October 2007, 26 patients (pts) with 

non-metastatic prostate cancer were treated with IORT before prostatectomy 

as part of their surgical procedure. Median age was 62.5 years (range 50- 

73). Ten pts were classified as ≤T2c, 16 pts as ≥T3. The median iPSA 

was 13 ng/ml and the median bioptic Gleason Score was 7. According to 

NCCN 2007, risk group distribution was as follows: intermediate risk 2 pts 

and high risk 24 pts. A total of 11 pts were treated with neoadjuvant hormones. 

Prostate dimensions were measured with intraoperative ultrasound 

in order to select the electron beam energy and the applicator size. IORT 

was delivered by a mobile linear accelerator in the operating room, using 8- 

10 MeV electron energies and 5-7 cm diameter applicators. The prescribed 

dose was 12 Gy at the 90% isodose. Three months later, postoperative external 

beam radiotherapy (EBRT) was prescribed to the prostatic bed alone 

and whole pelvis in case of pT3-4 pN0 and pN1, respectively. 

Results: According to the Memorial Sloan Kettering Cancer Center nomograms, 

the mean preoperative probability of organ-confined disease, extracapsular 

disease and lymph node involvement were 8%, 40% and 25% respectively. 

Postoperative histological findings were as follows: median GS 8, 

pT2 7 pts, pT3 16 pts, pT4 3 pts, pN0 14 pts, pN1 12 pts. Organ confined 

disease was diagnosed in 4 pts and no further radiation treatment was prescribed. 

Postoperative pelvic and prostatic bed EBRT were planned in 12 and 

10 pts, respectively. No patients had major acute rectal toxicity. Thirteen pts 

had G1 acute toxicity and only 1 patient had G3 urinary toxicity after IORT 

due to the development of jatrogenic monolateral uretheral stricture. No increased 

risk of urinary incontinence was recorded. After a median follow up 

of 17 months only 1 patient had evidence of biochemical relapse. 

Conclusions: IORT delivered before prostatectomy appeared a feasible and


safe approach for locally advanced prostate cancer, but longer follow-up is 

needed to evaluate late toxicity and clinical control. 

1040 poster 

IS IMRT BETTER THAN 3D CONFORMAL THERAPY FOR PROSTATE 

CANCER? A DOSIMETRIC COMPARISON 

C. Buckey 1 , S. Stathakis 1 , G. Swanson 1 , P. Mavroidis 1 , F. C. Su 1 , N. 



Purpose: This study compares and evaluates radiation therapy plans for 

prostate cases using both 3D conformal treatment (3DCRT) plans and IMRT 

plans, to ascertain if there are dosimetric advantages to IMRT, given the current 

constraints. Planning system, energy and dose volume constraints were 

varied, to find the most ideal combination. 

Materials: A single physician outlined the prostate (GTV), rectum, bladder, 

femoral heads and penile bulb of 10 consecutive prostate patients. 3DCRT 

plans, using 6 MV and 18 MV photons, were created with the Pinnacle treatment 

planning system (TPS). IMRT plans were generated by the Pinnacle, 

HiArt Tomotherapy, and Corvus TPSs, using two sets of constraints: from 

RTOG study 0415, and from Fox Chase Cancer Center (FCCC). 

Results: By comparing the plans in terms of dose statistics and dose volume 

histograms we observed that the 3DCRT was able to meet the RTOG 

dose constraints. The dose to critical structures was comparable, independent 

of the TPS. Dose homogeneity of the PTV was better achieved with the 

RTOG IMRT plans than 3DCRT plans, but was not as good for the FCCC 

IMRT plans. As neither criterion specify what is an acceptable DVH slope for 

the target, or what hot spots and cold spot are acceptable, this may not be 

problematic. The 3DCRT plan could be further improved if a better choice 

of beam angles was made. Dose to penile bulb is not a limiting factor when 

creating the 3D and IMRT plans based on RTOG criteria, but mattered greatly 

for the FCCC plans, influencing time and complexity. 

Conclusions: The plans were evaluated for: (i) ability to deliver 95% of the 

dose to the PTV without significant variation, and (ii) for dose to the rectum 

and bladder. The 3DCRT plans were able to meet the RTOG criteria, which 

suggests the added time and expense of IMRT planning was not justified for 

these cases. However, it is also true that allowing the TPS to work toward 

the RTOG criteria achieved a more homogeneous dose inside the target volume. 

On average, Pinnacle created the plans with the least variation, with 

Tomotherapy close behind, and Corvus well last. 

1041 poster 

LATE EFFECTS 3-YEARS AFTER HYPO-FRACTIONATED RADIO- 

THERAPY OF PROSTATE CANCER - RESULTS FROM A PILOT 

STUDY. 

A. Widmark 1 , P. Bergström 1 , P. O. Löfroth 2 , B. Zackrisson 1 , L. Franzén 1 , 

P. Fransson 1 

1 DEPT.OF RADIATION SCIENCES, Oncology, Umeå, Sweden 

2 DEPT.OF RADIATION SCIENCES, Radiation Physics, Umeå, Sweden 

Purpose: Recent publications have shown that α/βnfor prostate cancer (PC) 

is low (1.5-3.0 Gy), suggesting that hypo-fractionated radiotherapy (hypo-RT) 

could be advantageous for the treatment of localised PC. This hypothesis is 

at present tested in a randomised study comparing hypo-RT (7 x 6.1 Gy) to 

conventionally fractionated RT (39 x 2.0 Gy). The present report is from a pilot 

study on 12 patients treated prior to the start of the randomised study. Aim: To 

evaluate the technique and to preliminary evaluate late effects, after hypo-RT 

with 7 x 6.1 Gy to 42.7 Gy in patients with intermediate risk PC. All hypo- 

RT fractions are given with IGRT technique using the BeamCath R○technique 

with CTV-PTV margins of 6 mm (4 mm rectum). In a comparative clinical 

group, four fractions were given with this technique, while the remaining 35 

fractions were given with 10-15 mm margins. The RT-schedules are based 

on near equal late toxicity in both arms (α/β=3 Gy). 

Materials: Twelve patients included in the pilot study were treated between 

April 2004 and November 2005. Four patients received concomitant hormonal 

treatment. Toxicity was evaluated with the validated Prostate Cancer 

Symptom Scale (PCSS) questionnaire at baseline and up to 3 years after 

treatment. The hypo-RT arm was compared with a historical population of 

patients treated with 2 Gy daily fractions up to 78 Gy. 

Results: One patient given hormonal treatment was lost to follow-up due to 

early death in CVS. One patient treated in November 2005 has only reached 

the 2-year follow-up. The hypo-RT patients had decreased bowel symptoms 

such as stool leakage, blood in stools, compared to those treated with 78 Gy. 

No differences between the Hypo-RT and 78 Gy were found regarding urinary 

problems. PSA response was seen in all 12 patients, but one patient had a 

PSA relapse at 24 months. A biopsy did not show any remaining malignant 

cells. 

Conclusions: Hypo-fractionated RT of PC seems feasible. Decreased late 

bowel toxicity was seen in the hypo-RT patients compared with patients 

treated with conventional fractionation. No differences were found regarding 

urinary symptoms. PSA response was satisfactory. 

1042 poster 

LATE RECTAL BLEEDING AFTER CONFORMAL RADIOTHERAPY 

FOR PROSTATE CANCER: NTCP MODELING 

T. Rancati 1 , C. Fiorino 2 , V. Vavassori 3 , M. Baccolini 4 , C. Bianchi 5 , F. 

Foppiano 6 , L. Menegotti 7 , A. Monti 8 , M. Pasquino 9 , M. Stasi 10 , G. Fellin 

11 , R. Valdagni 1 

1 

FONDAZIONE IRCCS - ISTITUTO NAZIONALE DEI TUMORI, Prostate 

Program, Milan, Italy 

2 

OSPEDALE SAN RAFFAELE, Medical Physics, Milan, Italy 

3 

OSPEDALE DI CIRCOLO, Radiotherapy, Varese, Italy 

4 

OSPEDALE VILLA MARIA CECILIA, Medical Physics, Lugo, Italy 

5 

OSPEDALE DI CIRCOLO, Medical Physics , Varese, Italy 

6 

ISTITUTO NAZIONALE DEI TUMORI, Medical Physics, Genova, Italy 

7 

OSPEDALE SANTA CHIARA, Medical Physics, Trento, Italy 

8 

OSPEDALE SANT’ANNA, Medical Physics, Como, Italy 

9 

OSPEDALE CIVILE ASL 9, Medical Physics, Ivrea, Italy 

10 

OSPEDALE MOLINETTE, Medical Physics, Turin, Italy 

11 

OSPEDALE SANTA CHIARA, Radiotherapy, Trento, Italy 

Purpose: to fit a normal tissue complication probability (NTCP) model to 

clinical outcome on G2-G3 late rectal bleeding (lrb) after radiotherapy (RT) 

for prostate cancer 

Materials: rectal dose-volume histograms (DVHs) and clinical data of 1119 

patients (pts) enrolled in the AIROPROS 0101 (547 pts) and AIROPROS 

0102 (572 pts) multicenter trials were considered. All pts were treated in 

supine position mostly with 3 or 4-field techniques: ICRU doses were between 

64 and 81.6 Gy (1.8-2 Gy/fr). 1029/1119 pts were treated with conformal 

techniques. Minimum follow-up was 36 months. Pts were considered as 

bleeders if showing G2-G3 lrb within 36 months after the end of RT. G2 lrb 

was scored if bleeding occurred >2 times/week or if pts received 1-2 blood 

transfusions and/or laser coagulations; G3 if pts reported daily bleeding.The 

Logit model with DVH reduced to the equivalent uniform dose (EUD) was 

considered for NTCP fit (LOGEUD model). The parameters for the NTCP 

model were fit to patient data using a maximum likelihood analysis (MINUIT 

software). The 68% confidence intervals (CI) of each parameter were also 

derived. 

Results: 86/1119 G2-G3 lrb were registered (28 G3 lrb): 45/547 in AIRO- 

PROS 0101 and 41/572 in AIROPROS 0102 population. The LOGEUD model 

well describes the clinical outcome and does not overfit the data. The risk of 

lrb is a function of EUD (calculated from DVH using n=0.085 (1D-CI 0.017, 

3D-CI 0.047, best fit result)). Using LOGEUD the relationship between EUD 

and NTCP can be described with a TD50=97.7 Gy (1D-CI 1.8 Gy, 3D-CI 10.8 

Gy) and a steepness parameter k=6.02 (1D-CI 0.028, 3D-CI 1.82). Qualitative 

as well as quantitative comparisons show that the model fit the observed 

lrb rates very well. The figure shows the LOGEUD NTCP curve with the 

(95%-1D CI) compared with the experimental clinical incidence. 

Conclusions: These results well compare with previous published NTCP 

fits to lrb.Our patient population was "inhomogeneous" and this was interesting 

from a modeling point of view as a wider spectrum of DVH shapes 

produces a variety of dose-volume combinations which is useful when fitting 

a NTCP model (which depends both on dose and on volume parameters).As 

a consequence of these results in terms of dose-volume constraints during 

3DCRT/IMRT optimisation, we may confirm the prevalent importance of the 

high-dose region (70-75 Gy) which should be coupled to some constraints 

in the intermediate dose range (around 50-60 Gy) to further reduce the risk 

of bleeding. The AIROPROS triasl were partially supported by a grant from 

Fondazione Italo Monzino, Milan, Italy

1043 poster 

LDR BRACHYTHERAPY WITH SEEDS AS MONOTHERAPY IN 

EARLY PROSTATE CANCER - THE LUND-MALMÖ EXPERIENCE - 

THE 100 FIRST PATIENTS 

M. Einarsdottir 1 , R. Blom 1 , O. Bratt 2 , G. Ahlgren 3 , H. Leek 4 , I. L. Lamm 

5 , E. Wieslander 5 , P. Munck af Rosenschöld 5 

1 LUND UNIVERSITY HOSPITAL, Oncology, Lund, Sweden 

2 LUND UNIVERSITY HOSPITAL, Urology, Lund, Sweden 

3 MALMÖ UNIVERSITY HOSPITAL, Urology, Malmö, Sweden 

4 MALMÖ UNIVERSITY HOSPITAL, Oncology, Malmö, Sweden 


Purpose: In our institution, LDR brachytherapy is one of many treatment 

modalities in the favourable group of low risk prostate cancer patients: Stage 


Johannesma 4 , P. Lambin 5 , F. van Gils 6 

1 

MAASTRO CLINIC, Datamanagement, Maastricht, Netherlands 

2 

ING REAL ESTATE INVESTMENT MANAGEMENT BELGIUM, Property 

Analysis, Brussels, Belgium 

3 

MAASTRO CLINIC, Clinical Physics, Maastricht, Netherlands 

4 

MAASTRO CLINIC, Datamanagement, Heerlen, Netherlands 

5 


6 

MAASTRO CLINIC, Radiotherapy, Maastricht, Netherlands 

Purpose: Accurate measurement of toxicity of radiotherapy treatment (RT) 

for prostate carcinoma is important in the development of more effective treatment. 

Questionnaires can yield valuable information in addition to clinical 

judgement of the physician. The International Index of Erectile Function (IIEF) 

was used to measure erectile function. New questionnaires were used to 

measure radiation cystitis (RC-scale) and radiation proctitis (RP-scale). Aim 

was to determine psychometric properties of the IIEF, RC and RP-scale. 

Materials: Patients treated with RT for prostate cancer completed IIEF, RC- 

Scale and RP-scale at regular times during and after RT. The IIEF consists 

of 15 questions with a higher score referring to better erectile function. The 

RC-scale has 10 questions on common signs of radiation cystitis and the RPscale 

uses 13 questions with symptoms of radiation proctitis. A higher score 

points to higher toxicity. A question was added to all questionnaires regarding 

satisfaction with current symptoms by asking how the patient would feel 

if symptoms remained the same (on a 7-point scale from terrible to happy). 

Data were available for 178 (IIEF), 336 (RC-scale) and 333 (RP-scale) patients 

together with total RT dose (68 or 72 Gy). An exploratory factor analysis 

with Varimax rotation was done. Reliability was calculated as the ratio of 

true score variance and total variance derived from a linear mixed regression 

model. Validity was determined from Spearman correlations between questionnaire 

scores and scores on the satisfaction item, and from differences in 

toxicity scores of both dose groups using the Mann-Whitney U. 

Results: The IIEF consists of 3 factors (ability for sexual intercourse, sexual 

activity and sexual satisfaction). The RC-scale also consists of 3 factors 

(urinary problems, urinary control and urinary frequency). The RP-scale consists 

of 4 factors (overall bowel movement, pain, abnormalities and control). 

The IIEF had good reliability (ratio above 0.6) and both RC and RP-scale had 

moderate reliability (ratio just below 0.4). Validity results are shown in table 1. 

Both Spearman correlations and results of the Mann-Whitney U show signs 

of adequate validity. 

Conclusions: Factor structure of three self-report measures of toxicity of RT 

for prostate carcinoma was determined and all questionnaires showed adequate 

reliability and validity. Next step would be to determine the correspondence 

with toxicity scored by the physician and the practical implications for 

follow up after RT. 

1047 poster 

MODELING OF EARLY PSA KINETICS IN INTERMEDIATE RISK 


G. Delouya 1 , D. Taussky 1 , T. V. Nguyen 1 , M. Jolicoeur 1 , C. Lambert 1 , M. 

A. Fortin 1 , J. P. Bahary 1 , S. Gauthier-Bizier 2 , P. Despres 1 

1 CHUM-NOTRE-DAME, Radiation-Oncology, Montreal, Canada 

2 UNIVERSITY OF MONTREAL, Department of Medicine, Montreal, Canada 

Purpose: Changes in prostate specific antigen (PSA) values within the first 

year after radiotherapy can predict biochemical outcome on later follow up 

years. Other robust indicators of outcome might be present in analyzing the 

behavior of the early PSA kinetics. We investigated this hypothesis by modeling 

the PSA response in patients treated with external-beam radiotherapy 

for intermediate risk prostate cancer. 

Materials: We analyzed the PSA history of 74 patients from our institution 

with intermediate risk prostate cancer ( Gleason 6 + PSA values of 10-20 or 

Gleason 7 + PSA values

1049 poster 

OUTCOME AND QUALITY (QOL) OF LIFE AMONG PATIENTS 

TREATED WITH RADICAL PROSTATECTOMY, RADIOTHERAPY 

AND KRYOTHERAPY DURING TEN YEARS. SEVEN YEARS FOL- 

LOW UP. 

K. Majunder 1 , Y. Brandberg 2 , B. Lennernäs 2 , C. Bergdahl 3 , J. Hugosson 

3 , I. Franck-Lissbrant 2 

1 KI, Department of Oncology and Pathology, Stockholm, Sweden 

2 GU, Oncology, Gothenburg, Sweden 

3 GU, Urology, Gothenburg, Sweden 

Purpose: To present QoL and outcome for all patients treated in Gothenburg 

during 1988 and 1998 with localized prostate cancer. 

Materials: All patients during 1988-1998. with histological verified adenocarcinoma 

of the prostate (T1-T3bN0M0) and treated with a curative intention 

were asked to participate in the study. The treatment alternatives were 

open retropubic prostatectomy (RPE), high dose rate (HDR) brachytherapy 

(2x10Gy) in combination with external beam radiotherapy (2Gyx25), external 

beam only (2Gyx35; EBRT) or kryotherapy (KT). Margin used for EBRT 

was 2 cm and 1,5 cm towards rectum. Six months of total androgen blockage 

prior to radiation treatment were common. Quality of life and side effects 

were monitored using EORTC QLQ C30+PR25 in the patient cohort (mean 7 

years after treatment) and in a control-group of 200 men. 

Results: In total 751 patients were identified (377 RPE, 209 EBRT, 113 HDR 

and 52 KT). 66 patients had deceased from prostate cancer (5,3%, 18%, 

3,5%, 8% respectively). Cancer specific survival was similar for RPE and 

HDR and lower for EBRT. QoL and side effects between HDR and RPE were 

similar. The RPE grup scored higher overall QoL (also higher then the controlgroup). 

The EBRT group reported higher frequency of side effects in several 

questions. Questionnaire completion complience was high (80%). Data 

analysis is currently ongoing and will be presented. 

Conclusions: External beam combined with HDR brachytherapy and RPE 

are two effective treatments for localized prostate cancer. Side effects and 

QoL are similar and acceptable in these two modalities. EBRT seems to 

have more side effects with the target-margin used. However, this is not a 

randomized study and patients in the EBRT group was older. There might be 

a selection bias among RPE and HDR patients. 

1050 poster 

OUTCOME RESULTS FOR POST-OPERATIVE SALVAGE RADIO- 

THERAPY 

J. Cortés-González 1 , E. Castellanos 2 , S. Levitt 2 , M. Hjelm-Eriksson 3 , A. 

Holmberg 1 , M. Marquez 1 , K. M. Kälkner 2 

1 KAROLINSKA INSTITUTE, Cancer Centrum Karolinska, Stockholm, Sweden 


3 KAROLINSKA UNIVERSITY HOSPITAL, Radiumhemmet, Stockholm, Sweden 

Purpose: Prostate cancer is the most common malignancy in men. Radical 

prostatectomy (RP) is the primary treatment for localized disease. Although 

the clinical results of RP are usually favorable, rising PSA is a challenge 

for the practitioner. Watchful waiting, Total androgen blockage (TAB), adjuvant 

radiotherapy (AR) and salvage radiotherapy (SR) have been utilized to 

deal with this problem. This report details the results of the Karolinska Radiumhemmet 

outcomes of post-operative salvage radiotherapy for prostate 

cancer. 

Materials: We retrospectively reviewed medical records of 176 patients with 

rising PSA after RP treated with SR between January 2002 and January of 

2007. We lost follow up for 21 patients. Age, Pre RP PSA, pre salvage 

PSA, pT status and Gleason sum, disease free survival after RP, and PSA 

doubling time were recorded for the remaining 155 patients. The RT Clinical 

target volume (CTV) was defined as the prostate and seminal vesicle bed. 

The delivered dose was 70 Gy with 2 Gy per fraction. The treated fields 

were designed so that less than 15 % of the outlined rectal volume could 

receive doses greater than 70Gy. The calculation of 3 years relapse free 

probability is based on Stephenson 04. Side effects are reported according to 

the Radiation Therapy Oncology Group (RTOG) toxicity criteria. PSA relapse 

was defined as any increase of PSA above nadir value after SR. 

Results: Median age was 63 (49-77) and median follow-up was 28 months 

(6-71 mo.). PSA relapse occurred in 23% of the patients (36). The median 

3 year relapse free survival was (0.74) using Stephenson’s nomogram. The 

median relapse free period was 13 months (6-47 mo.). The Recurrence rate 

was somewhat dependent on the pT. The recurrence rate for pT3 was 75% 

(27), pT2 22% (8) and pT4 3% (1). The median relapse free time after RP was 

9.5 months (2-87). The early Urinary RTOG toxicity score was 0 in 38%,I-II in 

59%,and 3% were grade lll-lV, the early chronic toxicity was 67%, 30 % , and 

3% respectively. The chronic toxicity was 70 %, 22%, and 8% respectively. 

The GI RTOG toxicity scale, early was 29%, 71%, and 0%. The Early chronic 

was 72%,24%, and 4%. The Chronic was 73%, 21%, and 6% respectively. 

Conclusions: After a rise in PSA following RP, a higher dose of SR might 

increase local control of prostate cancer with a slight increase in rectal complications.. 

In the absence of a randomized trial the appropriate dose of SR 

is still uncertain. 


1051 poster 

S 335 

PERMANENT SEED IMPLANTATION FOR LOW RISK PROSTATE 

CANCER PATIENTS


The figure shows a typical example of a summed rectum wall map of a patient 

for a complete radiotherapy treatment (77Gy). The top is the cranial side of 

the rectal wall, the centre is the ventral side of the rectal wall and left and 

right are the dorsal side. It can be seen that the high dose region is smaller 

for the GM (left) than for the BA (right) position correction protocol.Ninety nine 

percent of the prostate volume receives a mean cumulative dose of at least 

75.0 Gy in the GM protocol versus 70.5 Gy in the BA protocol. 

Conclusions: Online position verification with gold markers aimed for adequate 

treatment of the prostate is effective and does not increase the dose to 

the rectal wall. 

1053 poster 

POSTIMPLANT DOSIMETRY AND URINARY MORBIDITY AFTER 

PERMANENT PROSTATE BRACHYTHERAPY 

J. Schaefer 1 , G. Welzel 1 , F. Wenz 1 

1 MANNHEIM MEDICAL CENTER, UNIVERSITY OF HEIDELBERG, Department 

of Radiation Oncology, Mannheim, Germany 

Purpose: To evaluate the relationship between health related quality of life 

(HRQoL) regarding urinary morbidity and postimplant dosimetry after permanent 

prostate brachytherapy. 

Materials: The EORTC QLQ-PR25 and the modified ICS-male questionnaire 

were sent to 296 men treated with prostate brachytherapy at Mannheim Medical 

Centre, University of Heidelberg/Germany between June 1998 and 2003 

December. 258 patients were alive at time of assessment. Of 238 questionnaires 

(92% response rate) 231 were suitable for analysis (97%). Median follow 

up was 51 months (13-78 months). Postimplant dosimetry was based on 

CT-images taken 6 weeks after implantation of the iodine-125 seeds. Calculated 

parameters were prostate volume receiving 100% (V100), 150% (V150) 

and 200% (V200) dose, dose to 90% of the prostate volume (D90). 

Results: Patients with urge symptoms had higher values for D90, V100, V150 

und V200 as patients without urge symptoms. Patients with urinary incontinence 

and stress incontinence have larger prostate volumes. 

Conclusions: Prostate volume and D90 are relevant parameters for HRQoL 

regarding urinary morbidity. 

1054 poster 

POSTOPERATIVE OR SALVAGE RADIOTHERAPY: PRELIMINARY 

RESULTS IN 431 PROSTATE CANCER PATIENTS 

D. Zerini 1 , B. A. Jereczek-Fossa 2 , C. Fodor 1 , L. Santoro 3 , A. Minissale 1 , 

A. Vavassori 1 , R. Cambria 4 , F. Cattani 4 , C. Garibaldi 4 , G. B. Ivaldi 1 , F. 

Serafini 1 , B. Franchi 1 , B. Avuzzi 1 , V. D. Matei 5 , B. Rocco 5 , E. Scardino 

5 , G. Musi 5 , F. Verweij 5 , O. de Cobelli 6 , R. Orecchia 6 

1 


2 

EUROPEAN INSTITUTE OF ONCOLOGY - STATE UNIVERSITY, Radiotherapy, 

Milan, Italy 

3 

EUROPEAN INSTITUTE OF ONCOLOGY, Department of Epidemiology and 

Biostatistics, Milan, Italy 

4 


5 


6 

EUROPEAN INSTITUTE OF ONCOLOGY - STATE UNIVERSITY, Urology, 

Milan, Italy 

Purpose: To evaluate the outcome of postoperative (PORT) and salvage radiotherapy 

(SART) using 3-dimensional conformal two-dynamic-arc (3D-ART) 

or six-field (3D-6F) techniques in 431 prostate cancer patients. 

Materials: 258 patients received PORT (started < 6 months after radical 

prostatectomy, RP) and 173 patients were treated with SART for biochemical 

failure after RP. Median age, preoperative PSA (iPSA) and Gleason score 

(GS) were 66 years, 9.4 ng/mL, and 7, respectively. Median dose was 70 

Gy/35 fractions for both PORT and SART patients. 3D-6F and 3D-ART were 

applied in 25.1% and 74.9% patients, respectively. Biochemical failure was 

defined as post-radiotherapy PSA nadir + 0.1. 

Results: Acute toxicity included rectal (PORT G1-2 44.2%; G3 0.8%, SART: 

G1-2 42.2%, G3 1.2%) and urinary events (PORT G1-2 51.2%; G3-4 2.3% 

SART: G1-2 37.6%, G3 0%). Late toxicity included rectal (PORT G1-2 

14.7%, G3-4 0.8%, SART G1-2 15.0%; G3 0.6%) and urinary events (PORT 

G1-2 28.3%; G3-4 3.7%, SART G1-2 19.3%; G3 0.6%). After median 

follow-up of 36 months, failure-free-survival (FFS) including both biochemical 

and clinical failure, was significantly longer in PORT patients (86.3% vs. 

63.3%, p

1056 poster 

PRELIMINARY RESULTS OF LATE RECTAL AND URINARY TOX- 

ICITY IN A PHASE II RANDOMIZED STUDY OF CONVENTIONAL 

FRACTIONATION VS. HYPOFRACTIONATION ON PATIENTS WITH 

HIGH RISK PROSTATE CANCER. 

M. G. Petrongari 1 , S. Gomellini 1 , B. M. Saracino 1 , S. Arcangeli 1 , S. Marzi 

2 , V. Landoni 2 , L. Strigari 2 , G. Arcangeli 1 

1 IRE, Radiotherapy, Rome, Italy 

2 IRE, Physics, Rome, Italy 

Purpose: Several recent studies suggested a great sensitivity of prostate 

cancer to high dose fractions due to an estimated α/atio of 1,5-2 Gy. With estimated 

α/alues of 3 to 5 Gy in late responding normal tissues of the pelvis, 

theoretical modeling shows a stronger enhancement of tumor effect than of 

late complications for larger (and fewer) fractions in prostate tumours. The 

purpose of this study is to test this hypothesis by comparing the late complication 

rate of a conventional fractionation and a biologically equivalent hypofractionated 

regimen in the radiotherapy of prostate cancer. 


proven, high risk prostate cancer were recruited to this study. All 

patients received a total androgen deprivation (AD) for 9 months. A 3D conformal 

radiotherapy to prostate and seminal vesicles was started after two 

months of AD. Patients were randomized to receive 80 Gy in 40 fractions in 8 

weeks (control arm A) or 62 Gy in 20 fractions in 5 weeks, 4 fractions per week 

(hypofractionation arm B). Late toxicities were defined as those detected 6 or 

more months after the end of radiation treament, and were evaluated following 

the EORTC/RTOG score system. The rectal mucosa damage was also 

evaluated in all patients with a 3 grade score scale (slight edema and rare 

telangectasia, moderate edema and confluent telangectasia, and necrosis) 

by means of pre- and post-treatment recto-sigmoidoscopies performed every 

six months after the end of radiation treatment. 

Results: One hundred thirty seven patients with a follow-up longer than 6 

months, 70 in the control and 67 in the hypofractionation arm were evaluated 

for late toxicity. Grade ≥3 toxicity was experienced by 4 patients of arm 

A, 2 (1.5%) rectal and 2 (1.5%) urinary toxicity, and in 1 patient of arm B 

(1.5%) who experienced an urinary incontinence. The actuarial 2-year G ≥2 

late rectal toxicity was 18% and 13% in the hypofractionated and control arm, 

respectively (p= 0,30). The actuarial 2-year G ≥2 rectal mucosa damage was 

18% and 20% in the former and latter arm, respectively. The actuarial 2 year 

G2 late urinary toxicity was 19% and 7%, respectively, for the experimental 

and control arm, respectively (p= 0,15). 

Conclusions: From these preliminary results, the hypofractionation schedule 

seems to be as safe as the conventional fractionation for both rectal and urinary 

tissues, with a slight but not significant trend in favor of hypofractionation, 

thus confirming the hypothesis of the theoretical modeling 


1057 poster 

S 337 

PROGNOSTIC SIGNIFICANCE OF PATHOLOGIC SV INVOLVEMENT 

AND THE EFFECT OF ADJUVANT RADIATION THERAPY ON 

OUTCOME 

G. Swanson 1 , I. Thompson 2 , B. Goldman 3 , C. Tangen 3 , J. Chin 4 , E. 

Messing 5 , E. Canby-Hagino 6 , J. Forman 7 , E. Crawford 8 

1 

UTHSCSA, Radiation Oncology, San Antonio, USA 

2 

UTHSCSA, Urology, San Antonio, USA 

3 

SWOG STATISTICAL CENTER, Department of Biostatistics, Seattle, USA 

4 

UNIVERSITY OF WESTERN ONTARIO, Department of Surgical Oncology, 

London, Canada 

5 

UNIVERSITY OF ROCHESTER SCHOOL OF MEDICINE, Urology, Rochester, 

USA 

6 

WILFORD HALL MEDICAL CENTER, Urology, San Antonio, USA 

7 

WAYNE STATE UNIVERSITY MEDICAL SCHOOL, Radiation Oncology, 

Detroit, USA 

8 

UNIVERISITY OF COLORADO HEALTH SCIENCES CENTER, Urology, Denver, 

USA 

Purpose: After prostatectomy, high risk patients are more likely to recur. We 

evaluated whether patients with seminal vesicle (SV) involvement had worse 

outcomes than those with capsular penetration and/or positive margins only 

and whether SV positive patients benefitted from adjuvant radiation therapy 

(RT). 

Materials: SWOG 8794 found a significant benefit of adjuvant RT vs. observation 

among 425 high risk (SV positive and/or capsular penetration and/or 

positive margins) patients randomized post prostatectomy. Subgroup analysis 

on the effect of positive seminal vesicles was undertaken. 

Results: After adjustment for treatment arm, SV involvement was a negative 

prognostic factor regardless of capsular penetration and/or positive margins. 

SV positive patients had decreased overall, metastasis-free, and biochemical 

failure-free survival (p


1058 poster 

PROSPECTIVE MEASUREMENT OF ACUTE TOXICITY DURING 

PELVIC EXTERNAL BEAM RADIOTHERAPY AND HIGH DOSE 

RATE (HDR) BRACHYTHERAPY BOOST IN MEN WITH LOCALIZED 

PROSTATE CANCER STRATIFIED BY AGE 

R. Galalae 1 , E. Tharavichitkul 2 , F. Geiger 3 , I. Lembke 1 , B. Buschbeck 1 , 

B. Kimmig 1 

1 UNIVERSITY KIEL, Radiation Therapy, Kiel, Germany 

2 UNIVERSITY CHINAG MAI, Radiation Therapy, Chiang Mai, Thailand 

3 UNIVERSITY KIEL, Department of Paediatrics, Kiel, Germany 

Purpose: To measure prospectively acute toxicity in elderly versus younger 

population of pelvic teletherapy and HDR brachytherapy for prostate cancer. 

Materials: Toxicity was measured prospectively in 140 patients at initiation(t0), 

during(t1-t6), and 6 weeks after radiotherapy(t7) according the international 

CTC-criteria. Mean iPSA was 24 ng/ml, mean stage was T2c, 

and mean Gleason score was 6. Organ systems were recorded in scales and 

scored according to symptom intensity using a new developed measurement 

instrument. Scoring ranged from grade 0(no symptoms) to grade 5(death). 

The pelvic radiotherapy was applied conventionally fractionated to TD 50 Gy. 

The HDR brachytherapy boost was performed using Holm’s transperineal approach 

by transrectal ultrasound guidance. 2x15 Gy were applied in the CTV 

1(peripheral zone). Mean grades of all items grouped in 8 scales of toxicity 

were calculated. Univariate analyses by age cohorts (65+ versus 65- years) 

were performed using the t-test for equality of means. 

Results: Mean grade of all scales climbed longitudinally from 0.1 to 0.2(t1 

to t6), and dropped again to 0.1(t7). Generally, grade 1 and 2 symptoms 

were registered only. In grade 1 was not observed. Mean grade for diarrhea 

climbed from 0.1 to 0.5 (t1 to t6), and decreased again to 0.1at t7. No grade 

3 diarrhea or higher was observed. The univariate analyses by age revealed 

no significantly stronger toxicities among the elderly cohort in all scales of 

toxicity compared with the younger one (p-values 0.769, 0.288, 0.362, 0.842, 

0.656, 0.563, and 0.296). 

Conclusions: Combined pelvic 3D external beam radiotherapy and HDR 

brachytherapy for prostate cancer is excellent tolerated in the elderly population 

as well. The toxicity measurement according to CTC classification by the 

used instrument was feasible. 

1059 poster 

PROSTATE MR SPECTROSCOPY WITH SURFACE COILS FOR THE 

EVALUATION OF ANDROGEN DEPRIVATION THERAPY 

A. Zapotoczna 1 , J. Simpson 1 , G. Sasso 2 

1 TOWNSVILLE TEACHING HOSPITAL, Medical Physics, Townsville, Australia 

2 CENTRE MEDICAL DE FORCILLES, Radiation Oncology, Ferolles-Attilly, 

France 

Purpose: Magnetic resonance spectroscopy (MRS) of the prostate measures 

biochemical changes within the prostatic volume, with the cancer regions 

characterised by increased levels of choline, reduced citrate or both. One of 

approaches to prostate cancer therapy is neoadjuvant androgen deprivation 

therapy (ADT) prior to radical prostatectomy and 3D conformal radiotherapy. 

ADT influences the MRS result by changing the prostate metabolism, with a 

significant time-dependent loss of metabolites during ADT. An endorectal coil 

is routinely applied for prostate MRS. It improves the signal strength in comparison 

with surface coils, but its use has disadvantages including patient 

compliance, coil cost and organ deformation. The aim was to evaluate the 

feasibility of prostate MRS with surface coils at 1.5 Tesla for a non-invasive 

assessment of the effectiveness of ADT. 

Materials: Nineteen patients affected by high risk, localised, histologically 

confirmed prostate cancer with a high Gleason score (range 6-9) and mean 

PSA range of 16.04ng/ml (1.5-66ng/ml) were enrolled. Informed consent was 

obtained and study was given ethics approval. The MRI/MRS investigation 

was performed before and after five months of hormonal therapy, using a 1.5T 

clinical Siemens scanner. MRS acquisition involved pointresolved spatially localized 

spectroscopy (PRESS) with fat and water spectral suppression. 2D 

MRS was employed for the first five patients and 3D MRS for the remainder. 

The metabolites of interest, choline (Cho), creatine (Cr) and citrate (Ci), 

were extracted from those voxels containing significant signal and the ratio 

(Cho+Cr)/Ci was calculated. 

Results: Using surface coils, good or acceptable results of MRS investigations 

were obtained at the prehormonal investigation, with exception of 

patients, for which the presence of air in the rectum distorted MR spectra. 

The average, standard deviation, minimum and maximum value of the 

(Cho+Cr)/Ci ratio was 0.31, 0.15, 0.01 and 0.67; 0.36, 0.15, 0.03 and 0.66; 

4.62, 4.79, 0.52 and 19.39 for the normal peripheral gland, normal central 

gland and tumour areas, respectively. Cancer was considered present when 

the (Cho+Cr)/Ci ratio showed more than three standard deviations from the 

normal area. After 5 months of hormonal therapy, the prostate volume on MR 

decreased by an average of 47.4% (from 10.0 to 89.7%). As expected, there 

was a decrease in MRS signal. However residual cancer could be detected 

by elevated choline levels even in the absence of citrate. For the 3D investigations, 

patients with detectable citrate at MRS had also higher PSA levels 

than patients without detectable citrate. 

Conclusions: Both the 2D and 3D MRS is feasible with surface coils as 

receiver coils. After five months of ADT increased choline levels could still 

show the regions of residual cancer, and that this generally correlated with 

increased PSA levels. This finding suggests that prostate MRS is capable of 

providing metabolic information, even for those patients receiving ADT. 

1060 poster 

PSA KINETICS AFTER HIGH DOSE RATE BRACHYTHERAPY 

IN PROSTATE CANCER. LONG TIME TO PSA NADIR AND NO 

FAILURES SEEN FOR PATIENTS WITH PSA BOUNCE. 

L. Aström 1 , I. Turesson 1 

1 ONCOLOGY, Uppsala, Sweden 

Purpose: PSA nadir (nPSA) and time to nadir (tnPSA) after curative radiotherapy 

have received increasing interest as potential prognostic markers. 

The significance of a temporary PSA bounce has been discussed but not established. 

We here retrospectively analysed PSA patterns after curative treatment 

with external beam radiotherapy (EBRT) and high dose rate brachytherapy 

(HDR-BT) for patients (pts) with localised prostate cancer. 

Materials: Data from 241 pts treated from 1995 to 2003 were analysed. The 

median follow-up was 56 months (12-129 mo). Preirradiatory short hormonal 

therapy (HT) was given to 188 pts (78%). EBRT was given with 2 Gy fractions 

to a total dose of 50 Gy. HDR-BT was given in two 10 Gy fractions. Follow 

up was at regular intervals including PSA measurements. PSA failure was 

defined according to the Phoenix definition (nadir + 2 ng/ml). Biochemical 

failure-free survival rate (BFS) was calculated with the Kaplan Meier method. 

Results: The overall BFS at four years was 75%. PSA failures developed in 

64 pts and the median time to PSA failure was 27 mo. The median nPSA 

was 1 ng/ml) 

was seen in 28 pts. The median time to bounce peak was 15 months with a 

median value of 2 ng/ml (maximum 6 ng/ml). None of these pts developed a 

later PSA failure and their median tnPSA was 38 mo. 

Conclusions: After HDR BT a long time to PSA nadir was observed, particularly 

in pts with PSA bounce, without PSA failure, and in pts not receiving 

hormonal therapy. A temporary PSA bounce was associated with excellent 

prognosis. 

1061 poster 

RADIOTHERAPY AFTER RADICAL PROSTATECTOMY IN PROSTATE 

CANCER 

C. Lainez 1 , A. Vila 1 , A. Sanchez-Reyes 2 , N. Artola 1 , L. M. Moya 1 , J. C. 

Julia 1 , A. Pedro 2 

1 HOSPITAL PLATO, Radioterapia, Barcelona, Spain 

2 HOSPITAL PLATO, Unidad Radiofisica, Barcelona, Spain 

Purpose: This retrospective study present the outcome of patients treated 

wich adyuvant or salvage radiotherapy (RT) alter radical prostatectomy at our 

institution. 

Materials: 40 patients received radiotherapy alter radical prostatectomy between 

2001 and 2007. Patient age, margin status, Gleason score, pathologic 

tumor stage, postprostatectomy and preRT PSA levels, and time from RT to 

rise were analyzed. At the time of radiotherapy, no patients had clinical or 

radiologic evidence of metastatic disease. The planing target volume was the 

prostatic bed, except a patient who presented nodal involvement. All patients 

were treated using linear acdcelerator with multi-leaf,a median dose of 70Gy 

in 2Gy daily fractions. Patient with positives regional pelvic lymph nodes received 

a median dose of 50Gy to the whole pelvis. Hormonal therapy was 

associated in the worse risk patients. The follow-up evaluation after RT consisted 

of serum PSA testing every 3-6months. Toxicity was graded using the 

RTOG scale. 

Results: Median age was 65 years (51-78 years).Positive margin were documented 

in twenty five patients, gleason score ≥7 in 30 patients, patologic 

stage pT3 in 20 patients,the median postoperative PSA was 0.22ng/ml and 

the median preRT PSA was 1.56ng/ml. The median time from prostatectomy 

to RT initiation was 33 months ( range 1-166 months). All the patients treated 

in the immediate postoperative had pT3 or positive surgical margins. Adyuvant 

androgen ablation was given to 11 patients, median duration was 16 

months.Grade 1gastrointestinal acute toxicity was observed only one patient, 

none of the patients experienced late toxicity. The median follow-up from the 

end of RT for all patients was 20 months( range 3-46 ). The biochemical control 

rate was 80% (32 patients).8 patients developed a rising PSA level, 5 of 

8 patients received salvage radiotherapy and the median time to failure for all 

(8) was 16 months. 

Conclusions: Salvage RT after prostatectomy can rescue patients with rerurent 

disease, and it seem adyuvant RT improved biochemical relapse-free

survival por patients with high-risk (pT3 or positive surgical margins). No relations 

between risck factor have been carried out due little number of patients 

analyced. 

1062 poster 

RELATIONSHIP BETWEEN PROSTATIC APEX, SWANSON’S LINE, 

AND URETHRA. IMPLICATIONS IN PROSTATIC RADIOTHERAPY. 

S. Sabater Martí 1 , M. Aguayo 1 , S. Vilar 1 , M. D. M. Sevillano 1 , M. V. Villas 

1 , A. T. Nuñez 1 , M. Rivera 1 , R. Berenguer 1 

1 COMPLEJO HOSPITALARIO ALBACETE (CHUA), Radiation Oncology, 

Albacete, Spain 

Purpose: Prostatic apex is one of the major challenges when delineating 

prostatic radiotherapy treatments. Retrograde urethrography has become a 

standard method for such localicalization. We investigated the relationship 

between prostatic apex, Swanson’s line (the straight line bisecting the pubic 

symphysis), and the "beak" of the uretrhrogram. 

Materials: 1) Twelve planning pelvic CT scans were obtained with 3 mm slice 

thickness. Previous a retrograde uretrography was made. 2) Twenty-seven 

diagnostic sagittal T2 pelvic MR owning to the twelve previous patients and 

fifteen additional patients treated with radiotherapy for prostate cancer were 

reviewed. The following measures were made: a) perpendicular distance 

from the "beak" of the urethrogram to the Swanson’s line; b) perpendicular 

distance from the Swanson’s line to the prostatic apex on sagittal CT and MR 

views. 

Results: All except two patients had the "beak" of urethrogram placed on 

the Swanson’s line. In one patient, the "beak" was found 8 mm anterior to 

the line and in a second one, 5.5 mm inside the pelvic floor. Mean distance 

from the "beak" of urethrogram to the Swanson’s line was 0.21 (SD 2.92). A 

non-significant correlation (Spearman r = 0.35) was obtained between distance 

from the prostatic apex and the Swanson’s line measured on MR images 

compared to images CT (mean MR distance 7.51, SD 4.64; mean CT 

distance 6.99, SD 5.03). 

Conclusions: Our results show a homogeneous location of the "beak" of 

urethrogram when related to the Swanson’s line. The prostatic apex on our 

results appears a bit caudal than previously reported. Our measurement 

method employed can be a possible explanation of the discrepancy; and the 

difficulty to differentiate the prostatic apex to the surrounding tissues. Retrograde 

uretrography could be replaced by the Swanson’s line when prostatic 

volumes are delineated for a radical radiotherapy treatment planning. 

1063 poster 

RELATIONSHIP BETWEEN TREATMENT PLAN PARAMETERS AND 

PARTICULAR PROGNOSTIC FACTORS IN PROSTATE CANCER 

TREATED WITH HIGH-DOSE-RATE BRACHYTHERAPY (HDR-BT) 

AS A BOOST. 

A. Chichel 1 , M. Kanikowski 1 , J. Skowronek 1 , M. Dymnicka 2 , T. Piotrowski 

2 



Purpose: The study is to determine the relationship between dose values in 

the prostate, OARs and particular prognostic factors related to high-dose-rate 

brachytherapy of prostate cancer. 

Materials: 190 patients (age 52 81, average 67,2) with prostate cancer (T1- 

3N0M0) were treated with interstitial HDR-BT since July 2006 till July 2007 in 

Greatpoland Cancer Center. HDR-BT was administered as a boost after previously 

delivered 50 Gy dose from external beam radiotherapy. All patients 

were given 15 Gy to PTV (encompassed by prostate capsule) in one fraction. 

Prostate volume was also assessed in all patients. Accordingly to dose volume 

histograms (DVH) there were determined parameters as follows: Dmin, 

Dmax, Dmean, D90 (reference dose given to 90% of treated volume), V100 

(volume receiving 100% dose), V150 and V200 for prostate and Dmin, Dmax, 

Dmean, D10 (dose given to 10% of OAR) and V100 for urethra and rectum 

(OARs), respectively. The parameters were correlated with prognostic factors: 

age, staging (TNM), Gleason score, initial PSA level (i-PSA), number of 

needles and volume of the prostate gland. Statistical analysis was prepared 

with Spearman correlation index; significance level of p-value < 0,05. 

Results: The mean value of D90 was 91,3%, range 65,9 102,8%. Mean 

urethral D10 was 121,8%, range 78,8 152,9%. Mean rectal D10 was 81,3%, 

range 37,4 101,0%. There was found statistically significant relationship between 

staging (TNM), prostate volume, and number of needles used for implant 

and increased prostate D90 (better coverage) and decreased V200 (better 

dose distribution). Amongst prognostic factors there was only age which 

was, indirectly, related to increased urethral D10 and Dmax. No correlation 

was found between any prognostic factor and rectal wall DVH parameters. 

Conclusions: Increased prostate volume with improved D90 and greater 

number of implanted needles results in better target coverage (higher V100), 

better dose distribution (lower V200) and decreased dose delivered to the 

urethra (lower urethral D10, Dmax), with no evident influence on rectal wall. 

Further investigation with close follow-up should give an answer if the above 


corresponds with morbidity. 

1064 poster 

S 339 

REPORT ON THE EARLY EFFICACY AND TOLERABILITY OF 

I125 PERMANENT PROSTATE BRACHYTHERAPY FROM A UK 

MULTI-INSTITUTIONAL DATABASE 

J. Wylie 1 , D. Mitchell 1 , P. Mandall 1 , D. Bottomley 2 , P. Hoskin 3 

1 

CHRISTIE HOSPITAL NHS TRUST, Clinical Oncology, Manchester, United 

Kingdom 

2 

ST JAMES’S UNIVERSITY HOSPITAL, Clinical Oncology, Leeds, United 

Kingdom 

3 

MOUNT VERNON CENTRE FOR CANCER TREATMENT, Clinical Oncology, 

Northwood, London, United Kingdom 

Purpose: To report on patient selection, implant quality and biochemical 

outcome following I125 permanent prostate brachytherapy from a multiinstitutional 

database. 

Materials: A central database was established in 2003 and has recorded patient 

demographics, tumour characteristics, pre and post-implant parameters 

and supplemental therapies on all patients implanted at the Christie Hospital, 

Manchester, Cookridge Hospital, Leeds and Mount Vernon Hospital, Northwood, 

London since then. RAPID-Strand TM (Oncura) seeds were used in the 

majority. We review the database and report on patient selection, implant 

characteristics, urinary toxicity as assessed by International Prostate Symptom 

Score (IPSS) as well as catheterization and urinary stricture rates. Early 

biochemical failure free survival rates are calculated by both ASTRO (1997) 

and Phoenix (nadir + 2ng/ml) definitions. 

Results: 1535 men with a median follow-up of 21months were registered between 

January 2003 and October 2006. Patient selection is similar between 

centres with median age 64 (41-82), median iPSA 6.6ng/mL (0.1-57) and median 

Gleason 6 (3-9) noted. Neo-adjuvant hormonal manipulation is used in 

245 men (16%) of men for downsizing and 159 (10%) for intermediate/high 

risk disease. Median pre-implant values are comparable with a D90 of 179Gy, 

189.3Gy and 184Gy, V100 of 99.8%, 100% and 99.2%, and V200 values of 

17.9%, 21.9% and 24.1% at each respective centre. Post implant dosimetry 

is lower for all indices at all centres by up to 38% except for the V200 at 

1 centre which increases. A negative correlation between post-implant D90 

and change in prostate size after the implant (oedema + CT contouring uncertainty) 

is noted at two centres (Pearson’s -0.51, -0.46, +0.53) The IPSS 

increases from a median of 5 at baseline to 18, six weeks after implant, but 

is not significantly different to baseline values by 12months. 9% of men require 

catheterisation after implant for a median duration of 55days, but urinary 

stricture rates remain low at 1%. Actuarial biochemical failure free survival at 

2years is 94.4% and 94.5% for ASTRO and Phoenix definition respectively. 

There are no pre- or post-implant indices which consistently predict for a reduced 

ASTRO and Phoenix biochemical failure rate. 

Conclusions: This maturing database representing approximately one third 

of UK implants between January 2003 and October 2006 confirms the early 

efficacy and tolerability of prostate brachytherapy. Accrual to the database 

will stop after 2000 patients but follow-up will continue and long term outcome 

analysis is planned. 

1065 poster 

RESULT OF SALVAGE RADIOTHERAPY WITHOUT HORMONAL 

THERAPY FOR BIOCHEMICAL RELAPSE AFTER COMPLETE PSA 

RESPONSE FOLLOWING PROSTATECTOMY 

M. Soler Tortosa 1 , J. L. Monroy 1 , M. López Muñóz 1 , A. V. Navarro 

Bergadà 1 

1 UNIVERSITY HOSPITAL DE LA RIBERA, Department of Radiation Oncology, 

Alzira, Spain 

Purpose: Salvage radiotherapy (RT) is used to rescue patients with biochemical 

failure of PSA (bPSA) after radical prostatectomy. The purpose is to 

evaluate our results of radiation therapy in patients submitted who achieved 

complete PSA response and who have never been with hormonal androgenic 

blockage. 

Materials: Between 2001 and 2006, a single institutional retrospective study 

was conducted in 26 patients received salvage RT on prostate bed after relapse 

bPSA without androgen blockage. The median dose was 66,7Gy. Parameters 

analyzed prognostics were: PSA at diagnosis; pre-radiation therapy 

PSA, pTNM, Gleason score, status of seminal vesicles; margin status; perineural 

infiltration and time from biochemical relapse. 

Results: Median follow-up time was 38 months. The 96 % of patients showed 

histological adverse data. Univariate analysis showed following results: Free 

survival of clinical relapse and biochemistry ( Kaplan Meyer ) were 84 % 

and 50 % respectively. The PSA post irradiation reduced significantly (p< 

0,02). Gleason score was not predictive of failure. The time from surgery to 

biochemical relapse was statistically significant for radiation therapy response 

(p=0.0004). 

Conclusions: The irradiation of the surgical bed gets a good local and biochemical 

PSA control. According to our study we thought that patients with


adverse data after surgery would benefit with a program of postoperative therapy 

better than radiotherapy course after bPSA relapse. 

1066 poster 

SALVAGE BRACHYTHERAPY COMBINED WITH MICROWAVE 

HYPERTHERMIA FOR RECURRENT PROSTATE CANCER . PRE- 

LIMINARY RESULTS OF A PHASE I STUDY. 

N. Piotrkowicz 1 , J. Lyczek 1 , A. Kulik 1 , A. Kasprowicz 1 , M. Kawczynska 1 , 

E. Gruszczynska 1 , B. Czyzew 1 

1 CENTRE OF ONCOLOGY M.S.CURIE MEMORIAL INSTITUTE, Brachytherapy, 


Purpose: There is a strong biological background for combined hyperthermia 

and radiation therapy in cancer treatment. Optimal salvage treatment of 

locally recurrent prostate cancer after radical radiation therapy is still a matter 

of controversy. Considering hyperthermia as a potent radiosensitiser it seems 

reasonable to combine brachytherapy with hyperthermia. 

Materials: From june 2006 to march 2007 10 patients with biopsy proven 

prostate cancer relapse after definitive external beam or/and brachytherapy 

were treated using hyperthermia assisted brachytherapy. At least 3 months 

of MAB was applied in every case. Castration PSA levels in 9/10 cases were 

achieved. Mean time to relapse was 33 (12-72) months. Mean PSA level was 

5,8 ng/ml (1,4-7,2). Micro Selectron HDR and Oncentra Prostate system was 

used for brachytherapy while hyperthermia was performed with microwave 

BSD 500 system. The same plastic tubes were used both for irradiation, hyperthermia 

and temperature measurements. Total radiation dose was 30Gy 

in 3 fractions of 10 Gy every third week. Hyperthermia session lasting for 45 

minutes with temperature of 42 ◦ C and was performed together with every 

fraction of irradiation. 

Results: No treatment related severe acute reactions were observed. One 

case of mild bleeding was observed after tubes removal. In three cases acute 

urinary retention was seen. In two cases urethal stricture occurred. 

Conclusions: Preliminary results are very encouraging. Phase II study is 

planned. 

1067 poster 

SALVAGE RADIOTHERAPY FOR BIOCHEMICAL FAILURE AFTER 

RADICAL PROSTATECTOMY: LONG-TERM RESULTS FROM A 

SINGLE INSTITUTION. 

T. Budiharto 1 , S. Junius 1 , K. Haustermans 1 , J. Verstraete 1 , R. Oyen 2 , E. 

Lerut 3 , S. Joniau 4 , H. Van Poppel 4 

1 UH LEUVEN, Radiotherapy, Leuven, Belgium 

2 UH LEUVEN, Radiology, Leuven, Belgium 

3 UH LEUVEN, Pathology, Leuven, Belgium 

4 UH LEUVEN, Urology, Leuven, Belgium 

Purpose: Salvage radiotherapy (RT) is used to treat prostate cancer patients 

with a biochemical failure after radical prostatectomy (RP). This study aims at 

assessing the long-term results of patients treated with salvage RT in a single 

institution and at determining predictive factors related to PSA outcome. 

Materials: A retrospective review of 109 patients, diagnosed with a rising 

PSA after RP and treated between August 1998 and December 2004, was 

performed. Margin status, Gleason score, pathologic tumour stage, capsular 

invasion and perforation, vascular invasion, seminal vesicle invasion, pre-RP 

and pre-RT PSA, PSA doubling time pre-RT, time between RP and PSA failure 

and time from PSA failure to start of salvage RT were analysed. None of 

the patients received hormonal therapy (HT) concomitantly. All patients were 

treated with high energy photons (18 MV) using a 3D conformal RT technique 

to encompass the prostatic bed to a total dose of 66 Gy in 2 Gy fractions. 

Results: Median follow-up was 55.0 months. Median time from RP to PSA 

progression was 12.7 months. Eighty percent (n = 88) had undetectable PSA 

in response to salvage RT. The 5-year biochemical relapse free survival was 

48.8%. Median PSA at salvage RT was 0.15 µg/L (0.0 2.16) and the median 

post RP PSA doubling time was 0.4 years (0.15 2.03 years). On univariate 

analysis, significant predictors of PSA recurrence after RT were Gleason 

score ≥ 7 (p=0.016), negative surgical margins (p3 days/week and 7 patients 

are doing them

equired to determine continued compliance and the material impact on future 

sphincter function.If found to be effective it appears that implementing such a 

regimen in this patient population is feasible. 

1070 poster 

SPIDER-PROSTATE: MANAGING CLINICAL DATA OF PROSTATE 

CANCER PATIENTS TREATED THROUGH A MULTIDISCIPLINARY 

APPROACH BY A PALM BASED SYSTEM 

A. Errico 1 , G. Mantini 1 , L. Tagliaferri 1 , M. Balducci 1 , A. Di Rito 1 , S. 

Fersino 1 , V. Frascino 1 , S. Luzi 1 , E. Mazzeo 1 , G. C. Mattiucci 1 , N. Cellini 

1 

1 CATHOLIC UNIVERSITY - UNIVERSITY HOSPITAL "A.GEMELLI", Radiother- 

apy, Roma, Italy 

Purpose: Aim of this work is to introduce a multidisciplinary file shared developed 

in our Institution to improve data collection to obtain informations useful 

for clinical activity and research. 

Materials: From 2001 a team consisting of Programmer and Medical doctor 

studied a system to collect a clinical data. At the same time a multidisciplinary 

working team of our institution began the analysis of significant variables in 

prostate cancer. SPIDER-prostate (System for Patient Individual Date Entry 

and Recording in prostate cancer) is a system of filing that allows the 

collection, the search and management of clinical data of patients treated 

in different places and moments from specialized medical doctors. All the 

informations recorded are shared and updated on-line from all the medical 

doctors, also through palm and wireless technology. The clinical data can be 

selected from the consumer without the intervention of the system planner. 

Results: 869 patients treated with radiotherapy for histologically confirmed 

prostate cancer by 1994 to today have been filed from May 2005. The activate 

procedures concern: appointments for the staging exames; staging, 

radiotherapy, hormonal therapy and follow-up data collection, through the use 

of electronic form; planning of the tests or examinations of follow-up visits. 

These data are so available in real time, and they are useful directly from 

the statistic analysis softwares for research purpose. Furthermore, SPIDERprostate 

can interact with the patients central hospital database to acquire all 

the information about the patient’ hospitalization. The system can calculate 

the months of global survival, disease-free survival, biochemical recurrencefree 

and/or local recurrence-free survival and it identifies the patients lost to 

follow-up. Moreover, the system contains a mail system. Extremely useful 

results the function of the presentation synthesis clinical data, enjoyable also 

from palm, both for the single operator and for the weekly multidisciplinary 

clinical cases discussion meeting. 

Conclusions: SPIDER-prostate is a good tool for the on-line data collecting, 

allowing to overcome the obstacles represented by multiples places, times 

and formality of filing of the data, that are typical of any multidisciplinary treatment. 

1071 poster 

STOCHASTIC PATTERN OF MOTION OF THE PROSTATE 

J. Kindblom 1 , B. Lennernäs 1 , H. Syrén 2 , R. Iustin 2 


2 MICROPOS MEDICAL, Gothenburg, Sweden 

Purpose: The prostate is a common target for radiotherapy and it is 

well known to be a moving target. Electromagnetic systems described by 

Lennern995 are now in clinical use and the aim of this study was to evaluate 

possible pattern of motion in prostate movements using such a system. 

Materials: The Micropos Medical 4 dimensional (4D) localization system has 

been used in a clinical trial in 10 patients for tracking prostate motion with 

a resolution of 1,7mm. During the study the tracking antenna (transponder) 

was placed in the prostate for approximately 10-20 minutes and position information 

data was stored. This information show how the prostate moves 

over time; that is in 4D. 

Results: All patients showed movements of the prostate from 1 20 mm. 

Large errors (15-20 mm) were usually temporary. In one patient there was 

a clear increased displacement with time, in one patient a possible movement 

related to breathing were monitored, but most of the patients showed 

stochastic movements within 1-5 mm, see Figure and example from one patient 

below. 

Conclusions: The prostate is a moving target. There was no clear pattern of 

movements of the prostate in the study and it is clear that more studies must 

be initiated to evaluate 4D movements in the era of small target-margins and 

4DRT. 


1072 poster 

S 341 

SUBCUTANEOUS ADIPOSE-TISSUE THICKNESS IS A MORE AC- 

CURATE INDICATOR OF THE VARIATION OF THE INTERFRACTION 

PROSTATE POSITION THROUGHOUT RADIATION TREATMENT 

THAN PATIENT’S WEIGHT OR BODY MASS INDEX. 

J. Wong 1 , G. P. Zhanrong 1 , M. C. Scott 1 , U. M. Minoru 2 , W. R. Paula 1 , 

A. M. Ian 1 , C. P. Chee-Wai 1 

1 MORRISTOWN MEMORIAL HOSPITAL, Morristown, NJ, USA 

2 UAS ONCOLOGY CENTER, 1st Division of General Surgery, Kagosima, 

Japan 

Purpose: Recent clinical outcome studies on prostate cancer reported the 

influence of patient’s obesity on the biochemical failure rates of these patients 

following various treatment modalities. Recently, we reported a strong 

correlation between obesity (BMI) and variance of lateral prostate shift (1). 

Our result indicated that without IGRT, the target volume may not receive the 

intended dose. We follow up this study by examining the correlation of the 

interfractional positioning of the prostate glands with respect to the patients’ 

weight, body mass index and a newly introduced conceptsubcutaneous adipose 

tissue thickness. 

Materials: Subcutaneous adipose tissue thickness (SAT) is defined as the 

distance ( in centimeter) measured along the central axis from the anterior 

skin to the portion of the closest muscle group (for the AP direction with 

prostate cancer treatment set up, it would be the rectus abdominus muscle 

overlying the symphsis pubsis). We retrospectively analyzed 117 prostate 

patients who received 10 to 15 fractions of IGRT treatment using CT-on-Rails 

from January 2006 to December 2007 in the first course. The daily prostate 

shift data along with patient’s weight, BMI, and SAT were collected and analyzed. 

Results: Our data indicates that lateral target shifts tend to increase with 

weight or BMI whereas the AP shift tends to decrease with weight or BMI. The 

Spearman ranked correlation coefficients between shift and the three body 

parameters indicate that all three body parameters are negatively correlated 

with the AP shift but positively correlated with the lateral shift. While all three 

parameters are statistically significantly associated with patients’ lateral shift 

(p


1073 poster 

SYSTEMIC AND RANDOM SET-UP ERRORS IN RADIOTHERAPY OF 

PROSTATE CANCER USING KV-CBCT. 

M. Machánová 1 , V. Richter 1 

1 REGIONAL HOSPITAL LIBEREC, Oncology, Liberec, Czech Republic 

Purpose: IGRT means not only checking set-up accuracy and correcting error 

in particular fraction, but evaluation of results and implementation into further 

practice improve treatment quality. To recognize the impact of systemic 

and random set up errors is one of the crucial points. 

Materials: 468 kV-CBCT acquisitions in 110 prostate cancer pts were evaluated. 

Acquisitions were taken first 1-3 fractions and then once a week (not in 

all cases fully realized). We formulated a null hypothesis of the mean of setup 

errors equal to zero, corresponding to their random character, and tested 

this hypothesis by the two-sided t-test. 

Results: The mean of set-up deviations (calculated of their absolute values) 

were in laterolateral(LL) direction(dir) 0.25±0.20cm, in anteroposterior(AP) 

0.28±0.25cm, in craniocaudal(CC) 0.29±0.36cm. The calculated p values 

for the whole cohort were LL p=0.0085, AP p=0.0001 and CC p=0.640. We, 

therefore, refused the null hypothesis (on 5% significance level) in LL and 

AP dir and we consider the errors to be random in CC dir. The statistical 

evaluation is anyway different in individual pts: Lesser impact of systematic 

errors was observed in individual pts: 2pts in no dir, 2pts in only 1 dir. 

Conclusions: a/ Although the absolute mean of set-up deviation is similar 

on all 3 directions, different impact of systemic and random errors was recognized. 

b/ Statistical evaluation of the whole cohort has an essential impact 

on exploring systemic errors and improving set up procedures and quality 

assurance of the work in each department. c/ Observed results in individual 

pts were different with minor impact of systematic errors. This fact can 

be influenced by smaller number of evaluated values, but also by higher acquisition 

numbers in evaluated individuals (8-10) compared to the average 

of the whole cohort (4.25). d/ Impact of random errors shown in individual 

pts has clinical importance for new fractionation schedules. According to our 

observation regular set up evaluation and error correction using IGRT is a 

necessary condition in hypofractionated RT, the role of random error in each 

set-up grows up with lower number of fractions. 

1074 poster 

TARGET VOLUME SEGMENTATION DISCREPANCIES BETWEEN 

ULTRASOUND AND COMPUTED TOMOGRAPHY MODALITIES IN 

PROSTATE BRACHYTHERAPY 

M. Joyner 1 , T. Tynan 1 , A. Gutierrez 1 , S. Stathakis 1 , N. Papanikolaou 1 , 

G. Swanson 1 

1 CANCER THERAPY & RESERACH CANCER AT THE UNIVERSITY OF TEXAS 

HEALTH SCIENCE CENTE, Radiation Oncology, San Antonio, USA 

Purpose: Preplanning for prostate brachytherapy involves the determination 

of the shape and volume of the gland. Typically, this is performed with ultrasound. 

Due to the difficulty in visualizing the sources on ultrasound, post 

planning is typically performed utilizing CT scan. Given that the two imaging 

modalities visualize the prostate differently, and the implant is planned based 

on ultrasound, the accuracy of using CT for post planning can be called into 

question. The first step in delineating this is to determine whether there are 

indeed differences in the volumes determined by US and CT, which is the 

goal of this study. 

Materials: Between August 28, 2007 and March 12, 2008, 33 consecutive 

patients underwent prostate volume measurement in the dorsal lithotomy position 

via trans-rectal ultrasound using a BNK Leopard ultrasound scanner 

with 2.5mm slices. Images were imported real-time to a Nucletron Spot- 

Pro 3.1 brachytherapy treatment planning system. Following ultrasound, a 

CT scan (GE Medical, Milwaukee WI) was performed with the patient in the 

supine position using a slice thickness of 2.5mm. The prostate and urethra 

were segmented by the same physician on both the ultrasound and CT scans 

using the SpotPro TPS. Patient data was binned in 5cc increments using the 

ultrasound prostate volume. 

Results: Approximately 70% (23/33) of patients demonstrated a decrease in 

prostate volume when using CT as compared to US, indicating a discrepancy 

between modalities. Within this group, the average percent volume decrease 

was 23.3%. Figure 1 shows the percentage volume difference between CT 

and US for each patient as a function of the US-based prostate volume. For 

smaller volumes (25cc), 

the volume defined by CT was almost consistently 20% smaller than the US. 

Conclusions: Due to the increased difficulty in visualizing the prostate on CT, 

it is highly likely that prostate volumes based on CT contours will differ from 

those obtained from ultrasound contoursespecially those larger than 25cc. 

Preliminary trends indicate that CT alone could underestimate the prostate 

volume by up to 50% in small prostate gland sizes. These discrepancies in 

volume size can significantly impact the treatment planning and CT-based 

post implant dosimetry. Investigations are currently underway to further explain 

these discrepancies.

1075 poster 

TECHNICAL DESCRIPTION OF THE NEXT GENERATION ELEC- 

TROMAGNETIC POSITION DEVICE FOR 4D RADIOTHERAPY. 

B. Lennernäs 1 , S. Nilsson 2 , S. Levitt 2 , B. Rosengren 3 , J. Linder 3 , H. 

Syrén 3 , R. Iustin 3 


2 KI, Oncology-Pathology, Stockholm, Sweden 

3 MICROPOS MEDICAL, Gothenburg, Sweden 

Purpose: Electromagnetic positioning for 4D radiotherapy was first described 

by Lennernt al 1995. The first generation of electromagnetic positioning systems 

for clinical use have been presented during the last two years and the 

aim of this study is to evaluate the 2:nd generation Micropos Medical 4D localisation 

system (MM4DLS) 

Materials: The system is a combination of a removable antenna placed 

on the carbon-fibre-treatment/ simulator/ CT-top and a removable implant 

(transponder) placed in the patient. In this study the transponder was 

mounted on a XYZ-coordinator and the position of the coordinator can 

be compared with the position of the MM4DLS in 3D. Measurement in a 

10x10x10 cm cube was performed 1000 times with a sampling frequency 

of 10 Hz. The system was also tested in a clinical radiotherapy chain on the 

CT (Siemens), simulator (Varian Simulix) and treatment top (Medical Intelligence). 

Results: The resolution of the 2:nd generation is; average error in 3D 0.47 

mm; SD: 0.2; max 1.8 mm. Corresponding data for generation one is 

0,77mm; 0,58mm and max 6.6 mm respectively. The carbon-fibre treatment 

top did not interfere with the system during measurement. The implant and 

antenna system did not interfere with the CT and showed less interference on 

the dose planning CT image compared with gold seeds. 

Conclusions: The MM4DLS system generation two shows improvements 

compared to generation one. It has sub-millimetre precision, low maximum 

error, low image disturbance and can be used on standard clinical carbon 

fibre treatment. 

1076 poster 

TELETHERAPY WITH INTERSTITIAL BRACHYTHERAPY FOR 

LOCALIZED PROSTATE CANCER: IMPACT OF TIMING OF 

BRACHYTHERAPY ON THE INCIDENCE OF COMPLICATIONS 

P. Agoston 1 , G. Frohlich 1 , T. Major 1 , J. Lovey 1 , A. Somogyi 1 , J. Fodor 1 


Purpose: To investigate whether the timing of brachytherapy (BT) is associated 

with an increased risk of complications following definitive tele- and 

brachytherapy for prostate cancer. 

Materials: Between 2001. and 2006. 133 patients with clinically localized 

prostate cancer were treated with three dimensional conformal external beam 

irradiation (median prostate dose: 60 Gy) and interstitial high dose-rate Ir-192 

brachytherapy (median dose: 10 Gy). According the timing of brachytherapy 

patients were divided into two groups: in group A and B BT was delivered 

between 0-3. week and 4-7. week of teletherapy. Early and late complications 

data were registered prospectively according to RTOG / EORTC toxicity 

grading scale. Surgical interventions due to late genitourinary and gastrointestinal 

complications were also scored separately. Median follow-up time 

was 34 months (range:12-62). 

Results: Earlier BT was associated with higher incidence grade 2, 3 late 

genitourinal complications (p


1079 poster 

THE IMPACT OF PROSTATE AND SEMINAL VESICLE MOTION ON 

PLANNING MARGINS OF PROSTATE GOLD SEED PATIENTS 

D. Lim Joon 1 , A. Mercuri 1 , V. Khoo 2 , K. Daly 1 , J. McNamara 1 , R. Stewart 

1 , K. Wan 3 , A. Rolfo 4 , M. Bell 1 , R. Chee 1 


2 ROYAL MARSDEN, Radiotherapy, London, United Kingdom 

3 AUSTIN HEALTH- BALLARAT, Radiation Oncology, Ballarat, Australia 

4 PETER MACCALLUM, Radiation Oncology, Melbourne, Australia 

Purpose: The seminal vesicles (SVs) form part of the target in the RT treatment 

of prostate cancer either because of the significant risk of involvement in 

locally advanced disease or because of overt clinical invasion. While prostate 

motion and the associated margins have been documented, there is little information 

on SV verification. Greater movement of the SVs compared to the 

prostate, if uncorrected, potentially leads to geometrical target miss. The aim 

of this prospective study was to assess and compare SV motion with respect 

to prostate motion and to ascertain the appropriate margins for each target. 

Materials: The study population consisted of 10 patients with locally advanced 

prostate cancer and considered to be at risk with SV invasion or had 

clinically T3b disease. The average age was 71 years, with average PSA and 

median Gleason scores of 10mg/L and 8 respectively, and T stages from T2a 

to T3b. Following consent, 5 gold seeds were inserted trans-rectally into each 

patient. Of the 5 seeds, 3 were inserted into the prostate (right base, left mid 

gland, right apex), and 1 into each of the left and right SVs. All patients were 

treated to a dose of 78Gy in 39 fractions with IMRT. Daily orthogonal 2D EPIs 

were taken of each patient in treatment position prior to RT. Elekta I-View 

GT template matching software was used to verify EPIs with the reference 

image (simulation digitally reconstructed radiograph). Online verification was 

performed for each fraction using the 3 prostate seeds. Matches of the left 

and right SV seeds were performed offline for each of the 39 fractions �of all 

10 patients. The total standard deviation (SD) of systematic errors ( tot) 

and SD of random errors (σtot) were calculated, and the CTV-PTV margins 

for both the prostate and SVs were generated using a previously published 

formula (2.5Σtot + 0.7σtot). 

Results: The average correctional shifts (with ranges) and margins for the 

prostate and SVs in mm were: 

Conclusions: Positional variation of the prostate and SVs was observed during 

RT. We have found that SV motion is greater in the RL and AP directions 

than prostate motion. Consequently, the calculated PTV margins for the SVs 

were greater than the prostate margins, indicating that differential margins 

may be warranted. 

1080 poster 

THE IMPORTANCE OF THE HIGH-DOSE RATE BRACHYTHERAPY 

BOOST FOR PROSTATE CANCER 

G. D. Wilson 1 , Y. Hasan 1 , J. Demanes 2 , A. Martinez 1 

1 WILLIAM BEAUMONT HOSPITAL, Radiation Oncology, Royal Oak MI, USA 

2 CET CANCER CENTER, Radiation Oncology, Oakland, USA 

Purpose: Radiation dose escalation using combined external beam radiotherapy 

(EBRT) and high-dose rate brachytherapy (HDR) has significantly 

improved the outcome of locally advanced prostate cancer. The purpose of 

this study was to investigate the importance of the HDR boost in the overall 

strategy of treatment by studying different dose-escalating treatment protocols 

from two centers using biologically effective dose (BED) modeling. 

Materials: Data was pooled from William Beaumont Hospital (WBH) and the 

CET Cancer Center. The two centers differed in their approach to scheduling 

external beam treatment (EBRT) and high dose-rate brachytherapy. At 

CET, HDR was given as the first treatment (in 4 fractions) followed by EBRT 

two weeks later whereas WBH combined HDR in the first, second and third 

weeks of 46 Gy in 2 Gy fractions EBRT when three HDR implants were used 

or in weeks 1 and 3 when 2 implants of were employed. A total of 12 different 

schedules were compared. Multiple clinical endpoints were analyzed including 

overall survival (OS), disease-free survival (DFS), local recurrence (LR), 

incidence of distant metastasis (DM), cause-specific survival (CSS), clinical 

failure rate (CLF) and biochemical failure rate (BCF); the latter defined by the 

PSA nadir plus 2ng/ml. Patients were studied overall and as a function of risk 

group. The standard BED model was used and the α/β ratio was assumed 

be 1.5 Gy based on recent modeling 

Results: Although there is a general improvement in clinical outcomes as 

the BEDs increase, there are notable exceptions where increasing dose does 

not necessarily translate into better failure rates. Stratifying all patients by 

median total BED (199.2 Gy) was without clinical significance for any of the 

endpoints. However, in the high-risk patients (n=397), a high BED was correlated 

with better OS (p=0.0232) and DFS (p=0.0291). Stratifying all patients 

according to schedules with higher (>0.6) or lower (

with the bDFS at the univariate analysis (p=0,019 and p=0,02, respectively); 

at multivariate analysis, only PSA value showed a significant correlation with 

the bDFS (p=0,01). In the subset of pts with nodal risk ≥ 30% (39 PORT and 

32 WPRT), at univariate analysis only WPRT was significantly correlated with 

the bDFS (p=0,01). Five-year bDFS was 46% for the PORT group and 80% 

for the WPRT group. Analyzing the subset of pts with risk > 15%, the 5-year 

bDFS of WPRT group (80 pts and bDFS 74%) and PORT group (95 pts and 

bDFS 73%) did not result significantly different (p=0.8). 

Conclusions: In our experience, patients with risk of nodal involvement > 

30% submitted to WPRT achieved a longer bDFS with respect to those patients 

treated to PORT. 

1082 poster 

TOXICITY AFTER THREE-DIMENSIONAL RADIOTHERAPY FOR 

PROSTATE CANCER. 

L. Ziccarelli 1 , E. Cervo 1 , P. Indrieri 1 , F. Piro 1 , R. Siciliano 1 , P. Ziccarelli 1 

1 OSPEDALE MARIANO SANTO, Radiation Oncology, Cosenza, Italy 

Purpose: To analyze treatment complication for prostate cancer managed by 

three-dimensional conformal therapy. 

Materials: From 2006 to 2007, 54 patients underwent conformal radiotherapy 

for localized carcinoma of the prostate. Patients were stratified according to 

stage, Gleason score and presenting prostate-specific antigen level. Media 

age was 70 years; median baseline prostate-specific antigen level was 20.2 

ng/mL, and the follow-up period was 10 months. Toxicity was scored with 

adapted RTOG/EORTC criteria. Patients received 50 Gy to the prostate and 

seminal vesicles (PTV1) followed by a boost to the prostate only to 74 Gy with 

200 cGy/daily. 

Results: Acute toxicity was reported in 60% of patients. No grade 4 or 5 

acute toxicity was reported. In gastrointestinal tract 6,9% of patients had 

G1 toxicity, 18% G2 toxicity and 1% G3 (mucorrhea and bleeding). In the 

genitourinary tract the observed rate of G1 acute toxicity was 28%, G2 21% 

and G3 3%. 4% of patients had G2 gastrointestinal toxicity (diarrhea) and 4% 

had G2 genitourinary late toxicity (dysuria and pollakiuria). 

Conclusions: Conformal radiotherapy in prostate cancer is well tolerated, it 

permits to reach high doses with acute and late toxicity. 

1083 poster 

TRENDS IN THE NATIONAL PRACTICE OF RADIOTHERAPY FOR 

LOCALIZED PROSTATE CANCER IN JAPAN: A PRELIMINARY 

PATTERNS OF CARE STUDY REPORT 

K. Nakamura 1 , K. Ogawa 2 , T. Sasaki 3 , H. Onishi 4 , M. Koizumi 5 , M. 

Araya 4 , A. Okamoto 6 , M. MItsumori 7 , T. Teshima 6 

1 

FUKUOKA UNIVERSITY, Radiology, Fukuoka, Japan 

2 

UNIVERSITY OF THE RYUKYUS, Radiology, Okinawa, Japan 

3 

NATIONAL KYUSHU CANCER CENTER, Radiation Oncology, Fukuoka, 

Japan 

4 

YAMANASHI UNIVERSITY, Radiology, Yamanashi, Japan 

5 

FUJITA HEALTH UNIVERSITY, Radiology, Nagoya, Japan 

6 

OSAKA UNIVERSITY, Medical Physics Engineering, Osaka, Japan 

7 

KYOTO UNIVERSITY GRADUATE SCHOOL OF MED., Radiation Oncology, 

Kyoto, Japan 

Purpose: The patterns of radiotherapy for prostate cancer has been changed 

rapidly in Japan. The purpose of this study is to examine the characteristics 

and changes of the patterns of radiotherapy for prostate cancer. 

Materials: The Patterns of Care Study conducted a random survey of institutions 

nationwide in Japan. Detailed information were collected on prostate 

cancer patients without distant metastases who were irradiated during the 

periods 1996-1998 and 1999-2001, and a survey on patients who were irradiated 

between 2003-2005 is in progress. 

Results: A total of 1184 patient data were collected in this study. The patients 

were divided into main three groups: The Fresh Group (57%) was treated 

with radical radiotherapy with photon beams; the Surgery Group (20%) was 

treated after prostatectomy; and the Hormone-Refractory Group (15%) was 

treated after progression from hormonal therapy. Other patients (8%) were 

treated with particle therapy or brachytherapy. In the Fresh Group, there was 

a decline in the fraction of patients with T3-4 tumors, from 65% in 1996- 

1998 to 44% in 1999-2001 and 35% in 2003-2005. A median dose to the 

prostate was 65 Gy, 68 Gy, and 69 Gy in 1996-1998, 1999-2001, and 2003- 

2005, respectively. Hormonal therapy was combined in approximately 85% 

of patients. In the Surgery Group, the median radiation dose of 60 Gy did 

not change between periods, but the 2003-2005 results showed a decrease 

in the use of doses < 60 Gy. In the Hormone-Refractory Group, the median 

dose of 66 Gy were irradiated at the median PSA level of 10 ng/mL. Since 

2003, low dose brachytherapy has started as one of the treatment options. 

Conclusions: The characteristics of prostate cancer and the patterns of radiation 

therapy in Japan are changing rapidly. 


1084 poster 

S 345 

USE OF A CORRECTION FACTOR FOR VOLUME CHANGES 

DURING TREATMENT TO PREDICT FOR ACUTE RECTAL TOXICITY 

IN EXTERNAL BEAM RADIOTHERAPY FOR PROSTATE CANCER 

R. Dahmane 1 

1 HOPITAL NOTRE DAME, Radio-Oncology, Montréal, Canada 

Purpose: Rectal volume and position change often during a course of treatment. 

Miralbell et al. (IJROBP 2003) developed a correction factor to adjust 

for volume changes during treatment. We correlated acute rectal toxicity with 

dose-volume parameters of the whole rectum and the rectum wall with and 

without this correction factor in patients treated with external beam radiotherapy 

(EBRT) for prostate cancer. 

Materials: We analyzed 85 prospectively evaluated patients. Patients received 

between 66 and 76 Gy for either primary or recurrent prostate cancer 

with EBRT. Acute rectal toxicity (RTOG definition) was correlated with rectal 

dose-volume histograms (DVH) on the planning scan and with a DVH adjusted 

with a correction factor. The correction factor is a polynomial function 

correlating the initial rectal volume with the mean percentage of change in the 

rectal volume during treatment. Student t-test was used to compare between 

patients with (grade 1-2) or without (grade 0) rectal toxicity. 

Results: Of the 85 patients, 66 patients (78%) experienced grade 1-2 acute 

toxicity. The most important dose-volume parameter that could differentiate 

between patients with or without toxicity was the median rectum wall dose (p = 

0.018). Mean whole rectum dose (p = 0.047) and median whole rectum dose 

(p = 0.032) were also significant predictors of toxicity. The correction factor 

improved slightly the value of the V40 of the rectum wall to predict toxicity (p 

= 0.042 without and 0.036 with correction factor). 

Conclusions: The use of a correction factor for volume changes during treatment 

does not improve the ability of DVH parameters to predict for acute rectal 

toxicity. The median whole rectum and rectum wall dose differentiate best 

between patients with or without acute rectal toxicity 

1085 poster 

USE OF A LH-RH AGONIST TREATMENT IN COMBINATION WITH 

RADIOTHERAPY (RT) IN PATIENTS WITH PROSTATE CANCER. AN 

OBSERVATIONAL STUDY. 

C. Hennequin 1 , P. M. Lugagne 2 , P. Coloby 3 , P. Costa 4 , H. Achour 5 , E. 

Leutenegger 6 

1 

CHU SAINT LOUIS, Paris, France 

2 

CLINIQUE DES SOEURS FRANCISCAINES, Versailles, France 

3 

CH PONTOISE, Pontoise, France 

4 

CHU NÎMES, Nîmes, France 

5 

LABORATOIRES ASTRAZENECA, Rueil Malmaison, France 

6 

ABR PHARMA, Paris, France 

Purpose: In France, prostate cancer (PK) is the most frequent men’s cancer. 

Chemical castration is recommended for metastasis and locally advanced PK. 

Due to PK diagnosis at earlier stages and ages, an overview of the population 

receiving an LHRH agonist (LH-RHa) in France seems quite useful. 

Materials: A longitudinal 6-month follow-up and prospective observational 

study was set up with urologists and radiotherapists, between the end of 2004 

and November 2006. Patients were included during a consultation of LH- 

RHa treatment introduction. QoL was measured by QLQ-C30 questionnaire 

including PR25 module, at inclusion and 6 months later. 

Results: 901 patients, mean age 73 (±9), were included by 180 specialists 

(156 urologists, 24 radiotherapists). For 3% of patients, PK was diagnosed 

during the inclusion consultation. Regarding the others, PK had been diagnosed 

13 (±25) months earlier (median=2). TNM classification at inclusion 

was a localized PK for 26% of patients, locally advanced for 51%, and metastasis 

PK for 20%. Medical context described by physicians for introduction of 

LH-RHa was metastasis detection (32% of patients), adjuvant radiotherapy 

(30%), rising PSA (20%), local relapse (5%), age (10%). For the 265 patients 

treated in combination with RT, 9 (4%) were in the favorable D’Amico group, 

54 (20%) in the intermediate group and 202 (76%) in the high risk group. 

The physician objectives for combining LH-RHa with RT were: improved survival: 

29%; progression delay (40%); PSA decrease (23%); prevention of 

complications/symptoms (8%). LH-RHa treatment was associated with an 

anti-androgen for 75% of patients. Hot flushes prevention treatment was associated 

to LH-RHa for only 2% of patients. 92% of patients received information 

on LH-RHa treatment side effects; lifestyle recommendations were given 

to 40%. Side effects of LH-RHa were observed in 66% of patients, mainly hot 

flushes and erectile dysfunction. The number of totally active patients (ECOG 

index 0) increased from 13% at inclusion to 42% at 6 months (p

S 346 CLINICAL/DISEASE SITES : SARCOMA, 

1086 poster 

WHOLE PELVIC RADIOTHERAPY COMBINED WITH NEOADJUVANT 

ANDROGEN DEPRIVATION FOR THE HIGH-RISK PROSTATE 

CANCER. RESULTS OF THE PROSPECTIVE COMPARISON TRIAL 

P. Milecki 1 , B. A. Jereczek-Fossa 2 , M. Baczyk 3 , Z. Kwias 4 , A. Antczak 4 

1 WIELKOPOLSKIE CANCER CENTER, Radiotherapy, POZNAN, Poland 

2 EUROPEAN INSTITUTE OF ONCOLOGY, Radiotherapy, Milan, Italy 

3 MEDICAL UNIVERSITY, Department of Nuclear Medicine, Poznan, Poland 

4 MEDICAL UNIVERSITY, Chair of Urology, Poznan, Poland 

Purpose: to study whether use of neoadjuvant androgen deprivation therapy 

(N-ADT) combined with whole pelvic radiotherapy (WPRT) for high-risk 

prostate cancer patients was associated with survival benefit over prostate 

radiotherapy only (PORT). 

Materials: Between May 1999 and December 2004, 162 high-risk prostate 

cancer patients (one of the following factors: T3 or PSA> 20 ng/ml or Gleason 

score>7) were treated with three-dimensional conformal radiotherapy 

(3DCRT) combined with long-term androgen deprivation therapy (L-ADT). Patients 

were prospectively divided into group A: 70 patients treated with N-ADT 

and WPRT and then with prostate and seminal vesicles radiotherapy (PORT) 

plus L-ADT and group B: 92 patients treated with PORT plus L-ADT. Patients 

represented following stage of disease; T2c: group A= 20 (29%), group B= 44 

(48%), T3: group A= 50 (71%) and group B= 48 (52%). The average probability 

of metastases to pelvic lymph nodes calculated according to the Roach 

formula were 35% and 31% for the group A and B, respectively. Median total 

dose of 46.4 Gy (44 Gy - 50 Gy) was applied to WPRT and 70.2 Gy (66 

Gy 74 Gy) to PORT. The median follow-up duration was 44 months (6 - 84 

months) and 45 months (7 - 79 months) for group A and B, respectively. The 

RTOG-ASTRO Phoenix definition of biochemical failure was used. Actuarial 

survival rates were calculated using Kaplan-Meier method and the log-rank 

test was performed to verify the differences between rates. 

Results: No significant difference in overall survival (OS) was found between 

analyzed groups (p= 0.4). Significant differences were observed in univariate 

analysis favoring WPRT combined with N-ADT for cause specific survival 

(CSS) (p= 0.01), distant metastases free-survival (DMFS) (p= 0.01), and 

trend for the prolongation of biochemical progression free-survival (b-PFS) 

(p= 0.07). On multivariate analysis combined treatment (WPRT + N-ADT) 

(p=0.01), lower PSA level (p=0.01), and lower risk of lymph nodes involment 

(p= 0.01) were significantly associated with longer CSS. 

Conclusions: Our results showed that WPRT combined with N-ADT compared 

to PORT for high-risk patients resulted in improvement in CSS, DMFS 

and bPFS. No OS benefit was observed. The longer follow up is warranted 

to confirm these findings. 

Clinical/Disease sites : Sarcoma, 

1087 poster 

EFFECTIVENESS AND TOLERABILITY OF ADJUVANT TREATMENT 

IN PATIENTS WITH SOFT TISSUE SARCOMAS AND UNFAVORABLE 

PROGNOSTIC FACTORS. 

B. Pilecki 1 , J. Strojek 2 , A. Kamiñski 2 , M. Goleñ 1 , A. Wygoda 1 , M. Hutnik 

1 , K. Skladowski 1 , E. Chmielnik 3 

1 COMPREHENSIVE CANCER CENTRE MARIA SKLODOWSKA-CURIE MEMO- 

RIAL INSTITUTE BRANCH GLI, Radiotherapy Department, Gliwice, Poland 


RIAL INSTITUTE BRANCH GLI, Surgery Department, Gliwice, Poland 


RIAL INSTITUTE BRANCH GLI, Patology Department, Gliwice, Poland 

Purpose: The evaluation of multidysciplinary treatment which consists of 

wide excision of the tumor and postoperative concurrent chemoradiotherapy. 

Materials: Retrospective analysis was based on 41 patients with soft tissue 

sarcomas (STS) who were treated in Cancer Center in Gliwice beetwen 2003 

and 2006. There were 22 (54%) males and 19 (46%) females in study group. 

Performance status of all patients was very good. The tumor site was extremity 

in 35 patients (85%). In 6 cases (15%) tumor was situated in the head and 

neck or trunk region. The most common histopathological types of tumors 

were fibrosarcoma and liposarcoma 22 (53%). Histopathologically,29 (71%) 

patients had high-grade tumors (G2,G3), and 12 (29%) had low-grade tumors 

(G1). Superficial sarcomas were recognized in 24 cases (58%) and the deep 

ones in 17 (42%) cases. According to the TNM system, 31 (76%) tumors 

were in T2 stage (>5cm), and 10 (24%) tumors were in T1 stage (

tasis were analyzed for local recurrence rate in relation to surgical margins 

and radiotherapy, occurrence of metastases and survival.Thirty-three primary 

and metastatic myxoid liposarcomas in 15 patients were treated with radiation 

therapy on the Department of Oncology University of Gothenburg. Twentyseven 

of the 33 tumours were surgically removed after preoperative radiation 

(3446 Gy) while 6 tumours were treated with radiotherapy alone (4460 Gy). 

Tumour size was measured by CT or MRI before and after radiotherapy in 30 

tumours. 

Results: In the SSG material 22% of the patients had primary surgery outside 

the sarcoma centre. No wide surgical margins were achieved in this group in 

contrary to 45% with wide margins at sarcoma centres. Despite non-wide 

surgery, only 58% of the high-grade lesions were treated with postoperative 

radiation therapy. The local recurrence rate in this group, if not irradiated, was 

47% and with postoperative radiation the local recurrence rate was 19%.Radiation 

therapy of myxoid liposarcoma at the Department of Oncology, University 

of Gothenburg, resulted in a median reduction in tumour volume of 53% 

in 23 of 30 irradiated tumours. All 27 surgically removed tumours revealed 

histological features of radiation response. The most striking morphological 

changes were lipogenic maturation, paucicellularity and hyalinisation. 

Conclusions: Patients with liposarcomas should be treated at specialized 

centres and postoperative radiotherapy is indicated for high-grade lesions. 

Radiation treatment often leads to significant volume reduction in myxoid liposarcomas 

and tissue response with a high degree of lipogenic maturation. 

Radiation treatment may be a useful preoperative option to increase 

resectability and could be used as a sole treatment in inoperable instances. 

1090 poster 

NEOADJUVANT TREATMENT IN SOFT TISSUE SARCOMAS 

B. Detti 1 

1 CAREGGI HOSPITAL, Department of Clinical Oncology, Firenze, Italy 

Purpose: The purpose of this study was to correlate clinical outcome with 

selected clinical parameters in a series of adults patients affected by softtissue 

sarcomas (STS). 

Materials: From 1998 to 2005, 51 inoperable patients with conservative 

surgery underwent neoadjuvant treatment (NT) at the University-Hospital of 

Florence. They received preoperative chemotherapy (p-CHT) with epidoxorubicin 

plus ifosfamide, associated to preoperative conventional external beam 

radiation therapy (p-EBRT) in 28 cases. Surgical resection was performed 3 

weeks after the completion of the NT. 

Results: At the time of analysis 17 patients out of 51 had died of cancer and 

34 were still alive. NT permitted to avoid amputation in 50 patients out of 51. 

Conclusions: NT in soft tissue tumours is still a controversial issue. On the 

basis of data presently available, preoperative treatment permitted in almost 

all patients limb sparing. 

1091 poster 

PALLIATIVE WHOLE LIVER IRRADIATION IN PATIENTS WITH 

HEPATOCELLULAR CARCINOMA 

M. Bialas 1 

1 MARIA SKLODOWSKA-CURIE MEMORIAL CANCER CENTER AND INST. OF 

ONC. GLIWICE, Radiotherapy, Gliwice, Poland 

Purpose: The aim of this study was to assess to effectiveness and tolerance 

of liver irradiation in patients with hepatocellular carcinoma. 

Materials: 10 patients (5 women and 5 men, 54-75 years old, median age 

68) were treated between 01.2003 and 03.2007 with external beam irradiation. 

All of them were irradiated to the total dose of 18 Gy with fraction dose 

of 1.8 Gy. 6 (60%) of patients were previously operated. All patients were 

retrospectively assessed for response, toxicity, and survival. 

Results: All patients completed the treatment. The most frequent acute toxicity 

was mild to moderate nausea, it was observed in 3 (30%) patients. Before 

treatment 60% of patients suffered from hepatalgia. 4 (40%) of patients 

demonstrated subjective response. Median duration of palliative effect was 

3 months (range 2-4 months). Median survival was 12 months (range 2-38 

months). 

Conclusions: Whole liver irradiation due to hepatoma can be an effective 

and safe method of palliation. 

1092 poster 

RADIATION THERAPY IN PATIENTS WITH ANGIOSARCOMA ? A 

RETROSPECTIVE ANALYSIS 

H. Garcia-Huttenlocher 1 , C. Timke 1 , J. Debus 1 , D. Schulz-Ertner 1 

1 UNIVERSITY OF HEIDELBERG, Radiooncology, Heidelberg, Germany 

Purpose: To retrospectively evaluate the outcome of patients with angiosarcoma 

treated with Radiotherapy (RT) at our institution. 

CLINICAL/DISEASE SITES : SARCOMA, 

S 347 

Materials: We analyzed treatment results in 27 patients with histological 

proven angiosarcoma, who received radiation therapy at our institution between 

1987 and 2007. The patient series included 15 male and 12 female 

patient, the median age was 60 years (range 27-80). Tumours were localized 

in head-andneck-region in 13 patients. The mediastinum was involved 

in 4, the retroperitoneum in 2, bony structures in 5 and the thoracic wall in 

3 patients, respectively. Seven patients had distant metastases at time of 

first diagnosis, one patient presented with lymph node metastases. Prior to 

RT, partial tumour resection was performed in 12 patients, 15 patients had a 

biopsy, only. Only one Patient was treated with adjuvant RT after complete 

resection. The remaining 26 patients had macroscopic tumour at the time of 

RT. Median radiation dose was 60 Gy (range 26 to 82 Gy). Seven patients 

had a history of a former irradiation in the past. Four of these 7 patients were 

reirradiated for local relapse after irradiation of an angiosarcoma and 3 patients 

were treated for a secondary tumour after breast cancer treatment 33, 

12 and 6 years ago. 

Results: Median follow-up was 11.75 months (range 1 to 299 months). At 

first follow-up, six to 8 weeks after completion of RT, 18 patients showed at 

least a partial remission, 2 patients had progressive disease and 2 patients 

showed a mixed response. Progression free survival probabilities at 1 and 

2 years were 45% and 22%, respectively. 13 patients were diagnosed with 

local recurrences, out of which six patients developed out of field recurrences. 

Overall survival was 42% and 33.6% at one and 5 years, respectively. 

Conclusions: Angiosarcomas are associated with a poor prognosis. Taking 

into consideration that all but one patient had macroscopic tumour residuals 

at the time of RT, results after RT can be considered in line with the RT results 

obtained in other sarcoma subtypes after incomplete resection. The poor 

prognosis is mainly related to their diffuse growth pattern and the fact, that 

angiosarcomas often occur in sites where a wide resection is impossible. 

The investigation of combined radiochemotherapy after incomplete resection 

is warranted. 

1093 poster 

RESULTS OF RADIOTHERAPY IN OSTEOSARCOMA 

R. Schwarz 1 , O. Bruland 2 , P. Schomberg 3 , A. Cassoni 4 , M. Kevric 5 , D. 

Carrle 5 , S. Bielack 5 

1 

MEDICAL CENTER HAMBURG-EPPENDORF, Radiation Oncology, Hamburg, 

Germany 

2 

THE NORWEGIAN RADIUM HOSPITAL, Oncology, Oslo, Norway 

3 

MAYO CLINIC, Radiation Oncology, Rochester, USA 

4 

MIDDLESEX HOSPITAL, Meyerstein Institute of Clinical Oncology, London, 


5 

KLINIKUM STUTTGART OLGAHOSPITAL, Pediatrics 5 (Oncology, Hematology 

und Immunology), Stuttgart, Germany 

Purpose: The experience of radiotherapy (RT) in the local treatment of osteosarcoma 

(OS) is limited. This is due to different reasons: OS is a rare 

tumor and surgery is the treatment of choice with high local control rates. 

Data of 100 patients with RT for OS from the international COSS-Registry 

(1980-2007) were analysed. Survival and local control rates at five years 

were calculated. Univariate and multivariate analyses were performed. 

Materials: The COSS-registry includes 3500 patients with histologically 

proven OS and other rare primary tumours of the bone. A total of 175 patients 

were irradiated over the period of 1980 to 2007 (5% of all patients). 

After exclusion of patients from analysis for different reasons, 100 patients 

were eligible. Median age was 18 (3-66) years. Indication for RT was a primary 

tumor in 66, a local recurrence in 11 and metastases in 23 patients. The 

location of irradiated tumors or metastases were: pelvis 33, lower extremity 

29, spine 13, head and neck 13, thoracic sites 10, and upper extremity 2 

cases. 94 Patients got external photontherapy, 2 pats. protontherapy, 2 pats. 

neutrontherapy, and 2 pats. intraoperative RT. Seventeen patients received a 

samarium-153-EDTMP therapy. Median dose for external RT was 55.8 Gy All 

patients were treated with chemotherapy in accordance to different COSSprotocols. 

Results: Median follow-up is 1.5 (0.2-23) years. 41 patients are alive, 59 patients 

died. Overall survival rates after RT for the whole group, for treatment 

of primary tumours, local recurrence, and metastases are 36 %, 55%, 15%, 

and 0% respectively. Patients with extremity tumours have a better survival 

than patients with axial tumours (55% vs. 25%, p=0.016). In 41 cases local 

control was achieved. Local control for the whole group is 30%. Local control 

rate for combined surgery and RT is significantly better than for RT alone 

(48% vs. 22%, p=0.002). Local control for treatment of primary tumours, local 

recurrence, and metastases are 40%, 17%, and 0% respectively. Local control 

for patients with additionally 153Samariumtherapy was poor. Use of dose 

over 60 Gy had no significant effect on local control. Prognostic factors for 

survival are indication for RT, RT plus surgery vs. RT alone and localisation. 

Prognostic factors for local control are indication for RT, and RT plus surgery 

vs. RT alone. 

Conclusions: Radiotherapy is an important option for local treatment of 

unresectable OS, after intralesional resection, or symptomatic metastases. 

Survival prognosis of theses patients is poor. Even the fact that many of 

these patients will die further on, they may benefit in terms of prolonged survival 

and prolonged local control. Combination of surgery, radiotherapy, and 

chemotherapy can be curative. Prognostic factors were identified.

S 348 CLINICAL/DISEASE SITES : TARGET AND VOLUME DEFINITION AND DELINEATION 

1094 poster 

SUCCESSFUL TREATMENT WITH TOTAL SKIN ELECTRON IRRADI- 

ATION AND DOXORUBICIN FOR CLASSIC KAPOSI SARCOMA 

M. Fundowicz 1 

1 GREATPOLAND CANCER CENTER, Radiotherapy, Poznan, Poland 

Purpose: Classic Kaposi Sarcoma (CKS) is a rare neoplasma and the best 

therapeutic method has not been determined to date. 

Materials: A 66-year old male in good health presented with asymptomatic 

skin lesions that had started to develope. Physical examination revealed numerous 

painless, bluish-red papules and nodules that coalesced in deepinfiltrated 

lesions affecting all his body. The most largest lesions were localized 

on his hands, chest, legs, soles of feet and between fingers, reaching 

the size from 1 to 3 cm.The separate bluish macula was also presents on 

mucosa in hard palate. The diagnosis of Kaposi sarcoma was established 

by histopatological and immunhistochemical examinations. HIV infection and 

dissemination of the disease to other organs were excluded. The treatment 

started with the total skin electron irradiation (TSEI), rotary-dual technique 

and 6 MeV electron beam, on the linear accelerator. The patient was administered 

1,5 Gy per day for the whole skin, four times weekly to the total dose 

of 34,5 Gy. Apart of that boost with 2 Gy per day were added on thighs, feet 

and hands up to 10 Gy, 20 Gy, 8 Gy respectively. During the therapy lesions 

gradually regressed. 

Results: Lesions on upper extremities and trunk disappeared, nodules on 

legs were flatten. The dry desquamation affecting lower extremities was observed 

as a side effect. The radiation changes were most intensified on 

hands, axillary and inguinal regions. The edema of legs persisted as well 

as the single macula on the mucosa. As the next step the chemotherapy 

with doxorubicin was given intravenously in 3 courses every three weeks. After 

chemotherapy the mucosa lesion turned pale and the edema of legs got 

smaller. Six months after the therapy the patient is in a healthy good conditions 

with remission of CKS. 

Conclusions: The presented combined treatment regiment with TSEI and 

chemotherapy with doxorubicin proved to be effective and well tolerated 

method of CKS therapy. 

1095 poster 

THE ROLE OF RADIATION THERAPY IN THE MANAGEMENT OF 

FACIAL DESMOID TUMORS 

N. Ozseker 1 , S. Ozden 1 , H. Tepetam 1 , Z. Ozgen 1 , N. Karadayi 2 , A. 

Mayadagli 1 

1 

DR. LUTFI KÝRDAR KARTAL EDUCATION AND RESEARCH HOSPITAL, 

Radiation Oncology, Istanbul, Turkey 

2 

DR. LUTFI KÝRDAR KARTAL EDUCATION AND RESEARCH HOSPITAL, 

Patology, Istanbul, Turkey 

Purpose: Desmoid tumors are rare connective tissue tumors that arise from 

fascia and musculoaponeurotic tissues. Desmoid tumors of the head and 

neck are very rarely reported for clinical features and outcome. With our 

treatment to the patient with desmoid tumor on maxillofacial area, we aimed 

to discuss about the relevance of radiotherapy in the treatment of desmoid 

tumors. 

Materials: Case report: The patient was a 33 years old woman. She presented 

with a mass on the glabella and between the eyes. We planned an 

external radiotherapy for the patient. It was done at total dose of 66 Gy divided 

in to 33 fractions (200 cGy/frx). Radiological complete response obtained by 

radiotherapy. The patient had been under follow up as "disease free" for 40 

months. Then she came with 3 cm a recurrent lesion on the right medial orbital 

area. This region had been protected for the eye protection during the 

radiotherapy. No treatment was applied yet. For the last one year she was 

followed up without further progression. 

Results: 

Conclusions: The treatment for desmoid tumors is negative line and surgery 

resection. When the existence of microscopic or macroscopic rest tumor 

treated with postoperative radiotherapy, local control rates increase. When 

the existence of surgery for the high functional or cosmetic losses. Therefore, 

radiotherapy may be a better alternative with similar control rates comparing 

to surgery which more functional or cosmetic losses. But radiotherapy margin 

must be large. 

Clinical/Disease sites : Target and 

volume definition and delineation 

1096 poster 

11C METHIONINE PET (MET-PET) IN TARGET VOLUME DEFI- 

NITION OF STEREOTACTIC RADIOTHERAPY(SRT) AND RADIO- 

SURGERY(SRS) OF INTRACRANIAL MENINGIOMA (WHO GRADE I) 

H. P. Bijl 1 , M. Heesters 1 , J. Pruim 2 , G. Wester 1 , R. Bolt 1 , M. van Dijk 3 , 

J. J. Mooij 3 , H. Langendijk 1 

1 UMCG, Radiation Oncology, Groningen, Netherlands 

2 UMCG, Nuclear Medicine, Groningen, Netherlands 

3 UMCG, Neurosurgery, Groningen, Netherlands 

Purpose: In meningioma long term tumor control with minimal side effects is 

achievable with SRT and SRS. However, precise target volume (GTV) definition 

is critical due to the possible infiltration into venous sinus, bone, along 

cranial nerves or vessels and dura. Meningiomas show a high 11C methionine 

uptake and can be visualized by PET. In this study we tested the hypothesis 

that the addition of MET-PET would result in a smaller GTV and to a dose 

reduction on critical brain structures. 

Materials: 20 patients were studied with pre SRT/SRS CT, GAD enhanced 

T1 3D MRI and MET-PET (ECAT HR+). GTV was defined by MR/CT only, 

MET-PET only and by the combination (final GTV). MET-PET GTV was defined 

based on the window at the tumor to brain interface. GTV’s calculated 

from CT/MR only, MET-PET only and final GTV were compared using paired 

samples statistics. Discrepancies in GTV areas were analyzed. In 5 patients 

with skull base meningioma SIMRT was performed using MR/CT GTV and final 

GTV. Mean dose reduction on hippocampus, chiasm and brain stem was 

calculated. Patients were treated with NOVALIS and BRAIN LAB Iplan/ Brainscan. 

Results: Meningioma were visualized in 18 patients, in 2 patients MET-PET 

was negative possibly due to small tumor volume. MET-PET defined GTV’s 

were significantly smaller compared to CT/MR based GTV’s, mean 8.7 cm3 

(range .83-27.9) and 15.9 cm3 (range 2.5-61.6)(p=.02). The addition of MET- 

PET did not led us to significantly reduce the final GTV compared to CT/MR 

(mean 12.1 cm3 range1.75-36.2 p=.06). MET-PET adequately identified the 

main tumor mass but not CT/MR suspected small extensions at the tumor 

margin below the PET camera resolution (5-6 mm) (along dural tails (89% 

of cases), blood vessels (11%) and cranial nerves (39%). In several cases 

larger extensions with diameter > 5 mm suspected on MR/CT , were negative 

on MET-PET. Here MET-PET showed no infiltration of cavernous sinus (35% 

of cases) sagittal sinus (22%) and skull base (17%). In 5 patients with absent 

cavernous sinus infiltration the final GTV was reduced compared to the 

MR/CT GTV and a radiotherapy dose reduction on hippocampus (mean dose 

31% (MR/CT plan) vs 23% (MR/CT/PET plan) , brain stem (24%vs18%) and 

chiasm (82%vs72%) was demonstrated. 

Conclusions: MET-PET GTV’s are smaller compared to MR/CT GTV’s although 

we did not significantly reduce final GTV. In patients with suspected 

cavernous sinus infiltration on MR/CT the addition of MET-PET reduced final 

GTV with a dose reduction on critical brain structures. 

1097 poster 

11C-CHOLINE PET/CT FOR INITIAL STAGING OF HIGH RISK 


J. Garcia 1 , V. Macías Hernández 2 , J. García-Ruíz 2 , A. Malet M 3 

1 CETIR, PET Unit, Esplugues de Llobregat, Esplugues de Llobregat, Spain 



3 CONSORCI SANITARI PARC TAULI, Radiology-UDIAT, Sabadell, Spain 

Purpose: The accuracy of abdominal CT and bone scan to detect nodal and 

distant metastases is quite low. Hipothesis: 11 C-choline PET/CT can localise 

false-negatives of the conventional exams. Theoretical benefits: [a] To avoid 

agressive local treatment in patients with metastases, [b] To adapt treatment 

volumes in order to irradiate with high dose selected lymph node areas, [c] To 

boost the dominant intraprostatic lesion. 

Materials: After Ethics Committee approval, informed consent was obtained. 

11C-choline PET/CT was performed in 10 patients prior to curative radiotherapy 

between 9/2006 and 3/2007. Inclusion criteria: T2-T4 N0 M0 and 

[Gleason 9 or (Gleason 7-8 + PSA>20ng)]. TRUS biopsy reports (4 per lobe) 

and pelvic MRI were compared. Probability of lymph node metastases and 

seminal vesicles involvement was calculated with the Roach formula. 

Results: Distant metastases were not found. PET/CT detected one iliac 

adenopathy that was false negative by MRI. However in another patient MRI 

showed one iliac adenopathy udetected by PET/CT. PET/CT found seminal 

infiltration in 40% of patients, similar to MRI. Perecentage of agreement between 

techniques: [a] T-stage: PET/CT vs DRE=0%, PET/CT vs MRI=30%, 

MRI vs DRE=20%; [b] Dominant lobe: PET/CT vs TRUS biopsy=80%, MRI 

vs TRUS biopsy=60%. RT plan was adapted to boost homolateral internal 

iliac area to 64 Gy in N1 patients. There is no late intestinal toxicity in this 

patients with 14.5 months follow-up.

CLINICAL/DISEASE SITES : TARGET AND VOLUME DEFINITION AND DELINEATION 

Conclusions: 11C-choline PET/CT seems to be unuseful to detect extraprostatic 

disease (T3a). The accuracy to show seminal involvement or to define 

the dominant lobe is quite similar to MRI. To locate initial lymphatic metastases 

makes feasible to deliver high dose in selected areas. Weakness of the 

study: Small sample, no histological confirmation of findings. 

1098 poster 

A METHOD FOR ACCURATE AND ROBUST SUV QUANTIFICATION 

WITH PET IN RADIATION TREATMENT RESPONSE EVALUATION 

A. Hoffmann 1 , J. van Dalen 2 , W. Oyen 2 , H. Kaanders 1 

1 



2 

RADBOUD UNIVERSITY NIJMEGEN MEDICAL CENTRE, Nuclear Medicine, 


Purpose: The standardised uptake value (SUV) is widely employed as a 

semi-quantitative index for tracer uptake with PET imaging. However, conventional 

methods to quantify SUV lack a solid theoretical basis and provide 

results that have a strong dependency on different imaging parameters: acquisition 

and reconstruction settings, lesion size, and tumour-to-background 

ratio (TBR). Therefore, these methods hamper the direct use of SUV quantification 

for response evaluation in radiotherapy, which may lead to misinterpretation 

in follow-up studies. It was our aim to develop an accurate and 

robust method for SUV quantification that is less susceptible to variations in 

said parameters. 

Materials: An iterative relative-threshold level method (RTL-SUV) was derived, 

based on the convolution of the measured point-spread function of 

the PET system with a sphere of diameter D. Validation of the method 

was performed using PET imaging (Siemens Biograph) of a Jaszczak phantom 

with 11 hollow spheres (D ranging from 4 to 60 mm) filled with F-18fluorodeoxyglucose 

(FDG), using different reconstruction settings (number of 

subsets, number of iterations, Gaussian filter). Activity concentrations were 

varied to obtain TBRs ranging from 1.5 to 10. The clinical feasibility of the 

method was assessed in patients with abdominal and lung lesions, by varying 

the number of iterations and subsets in OSEM2D reconstruction. Results 

were compared to conventional methods for SUV determination, in particular 

maximum-SUV and mean-SUV based on a 50% isocontour. 

Results: Phantom data validated our method: measured SUVs were consistent 

with the true activity concentration within 5%, and were independent of 

the TBR. Especially for small lesions (D


vanced oesophagus-, 46 pts of head-and-neck- and 89 pts of lung cancer) underwent 

standard positioning using AIO SolutionTM and thermoplastic mask 

fixation (ORFIT) and planning CT (Siemens Somatom Emotion 6 CT). After 

delivery of 45-50 Gy to the planning target volume (PTV) encompassing the 

contoured gross tumour volume (GTV) (primary tumour + affected regional 

lymphnodes) and entire involved and elective nodal regions a CT scan in the 

same position with mask was acquired again. Image fusion was performed in 

the XIO v. 4.2.0. planning system and the changed GTV1 was contoured on 

every axial slice. Volumetric and positional changes were determined. The 

boost volume (PTV1) and dose was defined taking into account the primary 

tumour extention, tumour shrinkage and geometrical reproducibility additionally 

to clinical data (changes of disease signs and toxicity) . 

Results: The individual mask had to be renewed in 8% o due to marked 

body or tumour changes. Gross tumour volume increased in great degree 

(in average 4 times larger (123-801%) than initially, ) in 3 NSCLC pts, and in 

further 5 cases (3 lung, 2 H&N) slightly, between 4% and 17%. 14 patients 

GTV (7 lung, 6 H&N and 1 esophage tumour) and had no significant difference 

of GTV and GTV1. Relevant tumour (10 esophage, 38 head-and-neckand 

76 lung cancer) shrinkage from 297 (± 684) cm3 to 88 (±14,6) cm3 

was detected in 124 pts. In terms of percentage of the initial volume, the median 

reduction was 30% (range, 6-87%). PTV, 1030 cm3 (± 832) could be 

decreased additionally to the deletion of only potential microscopic disease 

containing areas resulting in PTV1 of 497 cm3 (±246,5). 

Conclusions: Personalised mask fixation provides a good basis for accurate 

patient repositioning and image fusion. Individual evaluation of clinical data 

and anatomic changes prior to boost irradiation have significant impact on the 

complex therapeutical strategy and can lead to adapted treatment definition 

(target dose and volume). In the cases of tumour progression or no responce 

uneccessaire overtreatment could be avoided. The GTV to GTV1 loss proved 

to be mainly asymmetric, therefore the PTV1 should not be created only as 

auto margin around the initial GTV. Adjustment of the conformal radiation plan 

to the changed target and regional anatomy increases the treatment accuracy 

and therefore could be recommended during long course definitive irradiation 

of locally advanced tumour. Importance of inter-course in vivo radiosensitivity 

detection in patient selection for dose escalation should be further examined. 

1102 poster 

COMPARING THE AUTO-SEGMENTATION RESULTS OF 7 

PROSTATE PATIENTS WITH THE MANUAL SEGMENTATION RE- 

SULTS OF 7 RADIATION ONCOLOGISTS 

D. Huyskens 1 , P. Maingon 2 , B. Haas 3 , R. Bühlmann 3 , P. Kunz 3 , T. Coradi 

3 , A. Van Esch 1 , E. Salamon 4 

1 7SIGMA AND CLINIQUE STE ELISABETH, NAMUR, Tildonk, Belgium 

2 CENTRE FRANÇOIS LECLERC, Department of Radiotherapy, Dijon, France 

3 VARIAN MEDICAL SYSTEMS INTERNATIONAL AG, Department of Image 

Processing and Research, Baden-Daettwil, Switzerland 

4 CLINIQUE STE-ELISABETH, Department of Radiotherapy, Namur, Belgium 

Purpose: When trying to assess the accuracy of automatic segmentation 

modules for the prostate (Smart-segmentation v. 1.0.05, VMS) two origins of 

inaccuracies interfere: on the one hand the intrinsic accuracy/limitations of 

the automatic algorithm and on the other hand the inter-variability of volumes 

among clinicians. 

Materials: Seven Radiation oncologists were asked to contour seven 

prostate patients (resulting in 49 sets of contours). The Smart-Segmentation 

modules were run on these seven patients (resulting in 7 sets of automatic 

contours). The mathematical concept of Degree of Support (DoS) calculates 

if a given voxel is part of a certain hypothesis; the concept of DoS was introduced 

to calculate: a) the agreement among clinicians, b) the support given 

to contours of an individual clinician, c) the support given to the contours calculated 

by the automatic segmentation module. The DoS was calculated for 

a volume and on a slice per slice base. 

Results: The agreement among clinicians for the prostate and the bladder is 

comparable to the results obtained by the automatic segmentation algorithm. 

For both organs, the disagreement among clinicians increases towards the 

base and towards top of the organ. So does the support given to the automatic 

contours. The agreement among clinicians for the rectum is significantly 

larger than the support given to automatic segmentation algorithm. These 

results suggest that there is no direct method to improve the automatic contouring 

of the prostate and the bladder; the modelling of the rectum however 

could be improved 

Conclusions: By using the concept of DoS, we were able to quantify the 

accuracy of an auto-segmentation module within the variation of the clinician’s 

expertises. 

1103 poster 

DELINEATION FOR TUMOR BOOSTING IN PROSTATE CANCER 

BASED ON DYNAMIC CONTRAST-ENHANCED CT 

J. Korporaal 1 , C. Jeukens 1 , N. van den Berg 1 , G. Groenendaal 1 , M. van 

Vulpen 1 , U. van der Heide 1 

1 UNIVERSITY MEDICAL CENTER UTRECHT, Radiotherapy, Utrecht, 

Netherlands 

Purpose: To determine a (multi-focal) target for boosting, a ROI must be 

delineated. Dynamic contrast-enhanced (DCE) CT imaging has the potential 

to be useful in defining the boost targets, since it reflects neovascularization 

in the tumor. For radiotherapy it is important what the smallest volumes are 

that can be delineated and at which spatial resolution. 

Materials: 18 patients, with biopsy proven prostate cancer and scheduled for 

radiation treatment, underwent two DCE-CT exams within one week (referred 

to as CT1 and CT2). Imaging parameters: 64 slice, 120 kV, 200 mAs, iodine 

contrast agent (60 ml, 6 ml/s) followed by saline flush, subsequently 24, 10 

and 6 acquisitions with a time interval of 2.4, 10 and 20s respectively. All 

volumes were registered to the first pre-contrast acquisition of CT1 to remove 

prostate motion during the scans. Then, all volumes were reduced to 15 

nearly isotropic resolutions, varying from 0.002cc to 2.6cc per voxel. Tracer 

kinetics modeling was performed per voxel using the adiabatic approximation 

of the tissue homogeneity (AATH) model. For every resolution, all model 

parameters (flow, E, delay, Vextra and Tc) from CT1 and CT2 were compared 

with voxelwise Bland-Altman analysis. The within-patient standard deviation 

(wSD) is defined as the standard deviation of all differences divided by √ 2. 

Results: The flow value of the whole prostate (mean 17.7, range [10.0 32.5] 

ml/100gr/min) was lower than the flow found in regions suspected of tumor 

tissue (mean 37.9, range [23.6 87.7] ml/100gr/min). At voxel sizes larger 

than 0.5cc the wSD reaches a mean value of 4.0 ml/100gr/min, being the 

day-to-day variations in prostate blood flow and reflecting the measurement 

precision of the DCE-CT technique. At voxel sizes smaller than 0.5cc, the 

wSD will be dominated by noise and registration errors. 

Conclusions: The graph shows that the measurement precision of DCE- 

CT is dependent on the voxel size. A trade-off must be made between the 

wSD and the spatial resolution. At voxel sizes larger than 0.5cc, the wSD 

is sufficiently small to discriminate cancer tissue from healthy tissue. For 

tumors smaller than 0.5cc it is uncertain if boosting is required beyond the 

regular radiation dose in the prostate. The flow threshold at which a voxel is 

designated as tumor must be established using histological validation. 

1104 poster 

DOES GTV DEFINITION FOR RECTAL CANCER DIFFER SIGNIF- 

ICANTLY BETWEEN PLANNING CT AND MRI - A QUANTITATIVE 

SINGLE-CENTRE PILOT STUDY 

C. Dean 1 , J. Sykes 1 , A. Morgan 1 , S. Bacon 1 , R. Cooper 2 , D. 

Sebag-Montefiore 2 , P. Hatfield 2 , B. Carey 3 , S. Swift 3 , D. Thwaites 1 

1 

ST JAMES INSTITUTE OF ONCOLOGY, Medical Physics, Leeds, United 

Kingdom 

2 

ST JAMES INSTITUTE OF ONCOLOGY, Clinical Oncology, Leeds, United 

Kingdom 

3 

ST JAMES INSTITUTE OF ONCOLOGY, Clinical Radiology, Leeds, United 

Kingdom 

Purpose: There are indications that integration of MRI into radiotherapy treatment 

planning could improve tumour definition for rectal cancer due to its high 

soft tissue contrast. Differences in GTV shape, size and position between 

planning CT & MRI and between radiology & oncology were assessed in this 

study.


Materials: Seventeen pre-operative chemo-radiotherapy patients with rectal 

adenocarcinoma were included. CT and T2-w turbo spin-echo MRI were performed 

in the prone treatment position and the studies co-registered. Two 

radiologists by consensus (Rad) and two clinical oncologists (Onc1 & Onc2) 

separately delineated primary GTV on CT and MRI independently using diagnostic 

information. Delineations were then characterised by 3-D maximum 

extent, centre of mass (CoM) and volume. Disagreement was defined as [vol 

Avol B]/[max(vol A, vol B)]. The Lilliefors Test was used for normality and the 

non-parametric Wilcoxon Signed Rank Test to examine significant differences 

(alpha=0.05). 

Results: There were few significant differences in maximum extent between 

clinicians for CT. MRI revealed more, the largest being between Onc1 & Onc2 

by medians 0.5cm s-i (p= 0.045), 0.4cm a-p (p= 0.002) and 0.3cm l-r (p= 

0.015). Onc2 had the largest dimension differences between CT and MRI 

of medians 0.7cm l-r (p=0.004) and 1.0cm a-p (p=0.010). No significant differences 

in CoM were found between clinicians, although there were some 

small differences between modalities (median 0.1-0.2cm). Onc1 and OncAv 

CT volumes were significantly larger than Rad. MRI results, in direct contrast, 

showed significant differences between oncologists and between Onc2 

& Rad. Oncologists delineated significantly larger volumes on CT compared 

to MRI. Differences between modalities for radiology were not significant. Disagreement 

between Onc1 & Rad was significantly higher than between Onc2 

& Rad for CT. For MRI however, disagreement between Onc1 & Onc2 was 

significantly greater than between both Onc1 & Rad and Onc2 & Rad, in 

agreement with median volume differences (figure 1). 

Conclusions: In this institute the radiologists’ GTVs are independent of 

modality. Disparity for MRI-based definition is reduced between radiology 

& oncology but increased between oncologists compared to CT. Therefore, 

whilst the use of co-registered MRI does not offer an advantage for radiology, 

it does for oncology. With some training to reduce inter-oncologist variability, 

MRI-based GTV definition offers the possibility of smaller treatment volumes. 

1105 poster 

DOSE VOLUME HISTOGRAM EVALUATION OF PRONE AND 

SUPINE PATIENT POSITION IN EXTERNAL RADIOTHERAPY FOR 

GYNECOLOGIC CANCER 

A. M. Reig Castillejo 1 , M. Algara López 1 , P. Foro Arnalot 1 , N. Rodriguez 

de Dios 1 , X. Sanz Latiesas 1 , J. Lozano Galan 1 , J. L. López Guerra 1 , S. 

Villanueva 1 , J. Dengra 1 , J. Quera 1 , I. Membrive 1 

1 HOSPITAL DE LESPERANÇA, Radiation Oncology, Barcelona, Spain 

Purpose: Whole pelvic radiotherapy is used as standard treatment for gynecologic 

cancer. This treatment entails irradiation of small bowel, so, toxicity 

is very important. As gynecologic tumours are treated in a supine position, 

some investigators have treated patients in the prone position to displace 

S 351 

small bowell loops out of the pelvic fields. There are no data available concerning 

the positioning accuracy in the prone position for gynecologic malignancies. 

To perform a dose volume analysis of the small bowell depending on 

the patient position, comparing the volume receiving various levels of the prescribed 

dose in the two positions and to assess whether small bowell can be 

more effective spared when treating the pelvis in a supine or prone position. 

Materials: Between March 2007 to February 2008, 20 patients with gynecologic 

cancer received radiotherapy. Thirty minutes before simulation, patients 

ingested 75 ml of oral contrast. A CT scan was performed in the prone and 

supine position and slices were of one cm thickness each, from L3-L4 to the 

ischial tuberosities. PTV was delineated with one physician and had the following 

borders: L4/L5 superiorily, bottom of ischial tuberosities inferiorly, and 

15 mm outside the bonny pelvic laterally. And the lateral fields, with the same 

superior and inferior borders , but the anterior just infront of the pubic symphisis 

and the posterior in S2-S3 interspace .Small bowell was outlined on all 

CT scan slices. Mean dose administered was 45-50 Gy with 18 MV photons. 

Results: Mean volume between both positions were 362,9 ± 72,5% 

(p


asses primary visual cerebral cortex activation a blocked designed paradigm 

was used, consisting in four runs of subsequent rest and stimulation periods 

(blocks) each 76.4 s long (38.2 s the rest block and 38.2 s the stimulation 

block). During the rest period a white cross centered on black background 

was presented to the patient, whereas during the stimulation period 

a series of color geometric images (2 second per image) was showed.The 

data was processed using the free Matlab R○based software SPM5 from 

the Wellcome Department of Imaging Neuroscience University College London.Before 

statistics analysis, pre-processing steps (realignment, slice timing 

correction, anatomical-functional co-registration and smoothing) on EPI 

volumes was executed. A classical statistics analysis, based on the haemodynamic 

response function model of the BOLD effect, was carried out and a 

t-map (with a 0.05 family-wise corrected p-value) corresponding to the activated 

visual cortical areas as validate by the neuro-radiologist was extracted. 

Subsequently the two images (anatomical volume and activation volume) was 

co-registered with "mutual information technique with those from a RT dedicated 

CT scanner used for the dose planning of the treatment and used to 

define OAR that was identified with the activation volume. 

Results: The procedure leads to coregistration of functional MR and CT information 

with spatial precision of 2-3 mm. In this way we can give planning 

criteria and constrains to reduce late toxicity and functional disease to patients 

with long survival expectance. 

Conclusions: The data relative to adult population about the dose to avoid 

cognitive effect in brain treatment are poor. The question is what is the maximum 

deliverable dose to the OAR (the activated areas in our case) in order 

to maximally spare functional performances. The hippocampus role in arising 

of radiation induced dementia is known, so it is advisable not exceed a 5-10 

Gy dose in that area. Nothing can be said about other areas. Based on the 

literature regarding paediatric studies, the hypothesis for the maximum OAR 

dose is from 10 to 18 Gy. 18 Gy were used as constrain in OAR to plan the 

radiotherapic treatment. 

1108 poster 

GROSS TUMOR VOLUME DEFINITION IN TREATMENT PLANNING 

OF STREOTACTIC RADIOTHERAPY FOR BRAIN METASTASIS: 

DOSE COMPARISON STUDY WITH GADOTERIDOL 

T. Takahashi 1 , M. Shinbo 1 , M. Hondo 1 , K. Nishimura 1 , T. Yamano 1 , H. 

Yanagita 1 , H. Ohno 1 , T. Okada 1 , H. Osada 1 , N. Honda 1 

1 SAITAMA MEDICAL CENTER, SAITAMA MEDICAL UNIVERSITY, Radiology, 

Kawagoe, Japan 

Purpose: It is extremely important to identify GTV (Gross Tumor Volume) in 

treatment planning of Stereotactic Radiotherapy. We assessed GTV definition 

using enhanced axial images of MRI (1mm slice thickness). The aim of this 

study is to compare the definition of GTV using single-dose gadoreridol with 

that using double-dose gadoteridol, and we evaluated usefulness of doubledose 

gadoteridol in treatment planning of highly precise radiotherapy. 

Materials: Twenty-one lesions of 10 patients with brain metastases underwent 

axial MR images with gadoteridol in treatment planning of stereotactic 

radiotherapy for brain metastasis. We assessed GTV of each brain metastatic 

tumor on CT-MR fusion image of treatment planning after single and double 

dose administration of gadoteridol, respectively. 

Results: Each GTV of brain metastatic tumors was increased by using 

double-dose gadoteridol. The mean increased ratio of GTV by double-dose 

gadoteridol was 16.3 % in all tumors. Especially in tumors smaller than 1 ml, 

GTV was significantly increased by double-dose gadoteridol, and the mean 

increase ratio was 43.9 %. Futhermore, margin of tumors and border with 

normal brain tissue became clear by double-dose administration of gadoteridol. 

Conclusions: It is thought that double-dose administration of gadoteridol is 

useful for assessing GTV of brain metastasis in treatment planning of highly 

precise radiotherapy. 

1109 poster 

ICORG 06-35: PROSPECTIVE EVALUATION OF PET-CT SCAN IN 

PATIENTS WITH NON-OPERABLE OR NON-RESECTABLE NSCLC 

TREATED BY RADICAL 3-DIMENSIONAL CONFORMAL RADIATION 

THERAPY 

S. Gunn O’Connor 1 , R. McCloy 1 , B. McCafferty 1 , G. Rangaswamy 2 , C. 

Small 2 , G. Keane 3 , C. Collins 4 , A. Clayton-Lea 1 , E. O’Shea 1 , P. Thirion 

2 

1 


of 

2 


Republic of 

3 

ST. LUKE’S HOSPITAL, Department of Physics, Dublin, Ireland Republic of 

4 

ST. LUKE’S HOSPITAL, Department of Radiology, Dublin, Ireland Republic 

of 

Purpose: Positron Emission Tomography (PET) scans have demonstrated 

a significant increase in accuracy in the assessment of tumour extension in 

Non-Small Cell Lung Cancer (NSCLC), by establishing a more accurate diagnosis 

of local, regional nodal and metastatic tumour extension. Presently 

a PET scan is considered gold standard in pre-treatment assessment in patients 

(pts) with apparently localised NSCLC prior to considering any radical 

local approach, e.g. surgery or radical radiotherapy. This improved accuracy 

in tumour extension assessment has led to PET scan integration in the design 

of radiotherapy. Planning studies (Maastrich1) have demonstrated:- a significant 

difference between CT scan vs PET scan based volume and plan; a significant 

reduction of inter/intra-observer variation by using PET scan based 

tumour delineation techniques. 

Materials: ICORG 06-35, ’A prospective evaluation of PET-CT Scan in patients 

with non-operable or non-resectable NSCLC treated by Radical 3- 

Dimensional Conformal Radiation Therapy’, opened in August 2007 in St. 

Luke’s Hospital. The trial is co-ordinated by a Radiation Therapist (RT) and 

will employ a two-fold approach: - 1: Pilot study (n=10) to evaluate the technical 

feasibility of integrating PET-CT to planning-CT fusion into clinical practice 

in our institution. 2: A Phase II clinical trial (n=40, including 10 from the pilot 

study), to evaluate the safety of PET-CT scan based radiotherapy in terms of 

loco-regional control, through a precise evaluation of the intra-thoracic pattern 

of recurrence. 1) Conventional CT-scan Based Radiotherapy Technique 

All eligiable pts in this trial will undergo 3D-CRT planning and treatment while 

lying supine, breathing freely. The pt is set-up in the treatment position using 

a lung immobilisation device (lungboard). The pt then undergoes a noncontrast 

CT Scan (General Electric Lightspeed 4 slice CT) whilst breathing 

freely. The CT scan is acquired using the standard lung protocol, with a 3.27 

mm helical thickness and 1.5:1 pitch. An A/P and lateral topogram is taken to 

determine scanning margins. A single axial slice is taken to check for pt rotation 

prior to acquiring the complete number of axial slices. The axial slices 

are taken in 3.27 mm intervals and the tabletop height is recorded. 2) PET-CT 

scan Acquisition Pts then undergo a PET-CT scan in Blackrock Clinic, Dublin 

(our institution does not currently have PET-CT facilities) using a flat tabletop, 

the appropriate lung immobilisation device, and laser alignment to ensure 

that the patient is in the same treatment position with the same isocentre 

as the planning CT scan. A report of the PET-CT with specific reference to 

the primary tumour volume is issued by Blackrock Clinic. Two RTs from St. 

Luke’s Hospital attend the Blackrock Clinic for the PET-CT scan to ensure that 

the correct immobilisation and set-up procedures are used. A ’cold session’ 

(pre-injection phase) is used to familiarise the pt with the procedure. This enables 

the RTs to have minimal ptcontact post- injection. Once injected (’hot 

session’), the pt is radioactive and the RTs must adopt the ALARA principle. 

Exposure to the RTTs is recorded. Two separate plans, using the planning 

CT-GTV and the PET-CT-GTV are outputted. The pt will be treated using the 

PET-CT-GTV. All pts in the trial undergo standard post-treatment follow-up, 

including repeated 3 monthly CT scan of the thorax. The primary end-point of 

the pilot study will be the extent of successful delivery of PET-CT scan based 

radiotherapy - a rate of above 60% will be considered acceptable. 

Results: To mid-March, 10 pts have been recruited to the pilot study out of 

82 screened - 4 of these pts have subsequently been withdrawn as follows: 

- An unanticipated delay in receiving the PET scan report coupled with initial 

fusion software problems led to the first pt being withdrawn in order to avoid 

unnecessarily delaying the pt’s treatment start date. The second pt was 

unable to tolerate the lungboard. This subsequently led to an ability to tolerate 

this device being included as part of the eligibility criteria. One pt died prior to 

commencing treatment from a non-cancer related illness. One pt was shown 

to have rapid disease progression with associated deterioration, and received 

palliative RT. The process of fusing scans for the pilot study has proven quite 

challenging to date. This is due to: - Set-up errors, pts free-breathing, the time 

lapse between scans, the different duration of the scans (CT vs. PET), image 

quality, Lat Sup/Inf and Rotational movement. In addition, the importance 

of carefully selecting registration points and an appropriate threshold value 

(associated impact on volume) cannot be underestimated. 

Conclusions: Results from the pilot study will show the technical feasibility 

of integrating PET-CT to planning-CT fusion into clinical practice in our 

institution, and will determine whether or not we can safely advance to the 

next phase of this trial. 1De Ruysscher D et al. Int J Rad Onc Bio Phys 

2005;62:988-994 

1110 poster 

INHOMOGENEOUS MARGINS REDUCE THE PTV VOLUME IN IMRT 

FOR CERVICAL CANCER 

R. van der Put 1 , L. van de Bunt 1 , B. Raaymakers 1 


Purpose: In patients with cervical cancer the CTV consists of multiple structures 

and exhibits relatively large interfraction changes. To account for this 

motion and other positioning uncertainties during IMRT, a PTV margin is generally 

applied around the CTV to ensure adequate coverage. Since the motion 

characteristics vary across the CTV, the PTV would ideally be based on 

local statistics determined separately for each position on the CTV. This study 

proposes a new method to derive such inhomogeneous margins which can 

be used to construct a PTV. 

Materials: Seventeen patients with cervical cancer underwent an MRI exam 

before and weekly during IMRT. T2-weighted sagittal and axial scans were 

made on a 1.5 Tesla MRI scanner. This resulted in five sets of images per


patient. The CTV was delineated on all sets. The images for each patient 

were registered to the pre-treatment scan using the bony anatomy. The pretreatment 

CTV was resampled using manually placed landmarks and interpolation 

to provide 841 control points. For each patient the pre-treatment CTV 

was expanded along the gradient of the distance transform to create outward 

paths for each control point. The intersection of each path with the remaining 

four CTV’s defines the individual path lengths needed to generate a margin 

that accounts for interfraction motion and deformation. Statistical analysis on 

the combined patient data provides the generic path lengths needed to construct 

a new PTV. For evaluation a PTV for each patient was constructed with 

the proposed method and compared to a homogeneous margin of 15 mm 

and a previously reported method which derived anisotropic PTV margins 

from the boundaries of the CTV in the 6 main directions [1]. 

Results: The average PTV volume of the proposed method was 553 ml. For 

the homogeneous margin and 6 directions method the PTV volume was 725 

ml and 699 ml respectively. The average percentage of CTV volume covered 

by the PTV was 99.4%, 99.5%, and 99.6% for the proposed, homogeneous, 

and 6 directions methods respectively. 

Conclusions: Using a local margin to account for CTV motion, the PTV volume 

can be reduced by up to 24% compared to existing methods while maintaining 

similar coverage across treatment sessions.[1] L. van de Bunt et al. 

2007 Motion and Deformation of the Target Volumes During IMRT for Cervical 

Cancer: What Margins Do We Need? Int J Radiat Oncol Biol Phys 69 

388 

1111 poster 

INTEROBSERVER AND INTERMODALITY VARIABILITY OF 

PROSTATE AND SEMINAL VESICLES DEFINED BY COMPUTER- 

IZED TOMOGRAPHY AND MAGNETIC RESONANCE IMAGING 

G. Mazzarella 1 , M. Leone 1 , A. Bonanni 1 , F. Tortoreto 1 , R. Capparella 2 , 

R. Fragomeni 2 , B. Nardiello 2 , C. Guidi 1 , A. Petrone 1 , O. Caspiani 1 , L. 

Marmiroli 1 

1 

OSPEDALE "S. GIOVANNI CALIBITA" FATEBENEFRATELLI, ISOLA TIBERINA, 

Radiotherapy, Rome, Italy 

2 

OSPEDALE "S. GIOVANNI CALIBITA" FATEBENEFRATELLI, ISOLA TIBERINA, 

Medical Physics, Rome, Italy 

Purpose: The aim of this study is to determine the magnitude of the observer 

and scan related variation when delineating the prostate and the seminal vesicles 

(SV) in Computerized Tomography (CT) and Magnetic Resonance (MR) 

for radiotherapy treatment planning. 

Materials: Ten consecutive patients with localized prostate carcinoma underwent 

a CT and an axial MR scan (T2 images) in treatment position and 

conditions. Four radiation oncologists were asked to outline the prostate and 

SV independently, at first on CT and later on MR. The volumes were measured 

and the interobserver and interscan variability of the prostate and of 

the SV were evaluated. 

Results: In determining the interobserver CT variability, the mean CT-derived 

prostate volumes for the 10 patients were 50.31 cm3, 49.35 cm3, 47.09 cm3 

and 58.57 cm3 for observers 1, 2, 3 and 4, respectively; the mean CT-derived 

SV volumes were 15.7 cm3, 12.84 cm3, 13.72 cm3 and 15.00 cm3. The 

mean standard deviation (SD) of the different prostate volumes among all 

operators was ± 5.30 (10%), for the SV was ± 2.09 (16%). In determining 

the interobserver MR variability, the mean MR-derived prostate volumes were 

56.20 cm3, 46.44 cm3, 37.75 cm3 and 51.92 cm3 for observers 1, 2, 3 and 

4, respectively; the mean MR-derived SV volumes were 19.39 cm3, 13.61 

cm3, 14.03 cm3 and 13.99 cm3. The mean standard deviation (SD) of the 

different prostate volumes among all operators was ± 7.53 (16%), for the SV 

was ± 3.57 (27%). In determining the intermodality variability, the CT derived 

prostate volumes were larger than the MR derived volumes in 57% of cases; 

the mean ratio between CT volume and MR volume was 1.09 (SD 0.27). The 

CT derived SV volumes were larger than the MR derived volumes in 43% 

of cases; the mean ratio between CT volume and MR volume was 1.18 (SD 

0.62). 

Conclusions: In our experience, there is a tendency to outline a smaller 

prostate volume using T2 MR imaging than using TC, with an acceptable 

interobserver variability (16% of variability). Overall, operators were more 

confident with TC scans (10% of variability), despite all of them stated the 

advantage of the MR in delineating the apex of the prostate. A longer period 

of training with MR imaging of the prostate is needed. T2 MR imaging of the 

SV was considered not acceptable either in terms of interobserver variability 

(27%) either in terms of intermodality variability (62%). T1 MR imaging could 

probably add something to the correct contouring of the SV. 

1112 poster 

INTEROBSERVER CONCORDANCE FOR COMPUTED TOMOGRA- 

PHY TARGET VOLUME DELINEATION OF BREAST ELECTRON 

BOOST RADIOTHERAPY 

N. Rosenfelder 1 , M. Hawkins 1 , V. Wolstenholme 1 , G. Ho 1 , H. Urbanczyk 

1 , G. Ross 1 , D. Tait 1 

1 ROYAL MARSDEN HOSPITAL, Radiotherapy, London, United Kingdom 

S 353 

Purpose: Computed tomography (CT) planning could increase breast boost 

accuracy, when compared to clinical mark-up. Using CT we aim to examine 

variability in target volume delineation for electron boost planning in breast 

radiotherapy. 

Materials: Women receiving adjuvant whole breast radiotherapy (WBRT) and 

an electron boost after breast conserving surgery (BCS) were investigated. 

BCS using oncoplastic techniques was performed. As per local practice, 

WBRT was planned using CT data while the boost was defined clinically and 

delivered with electrons. 15 lumpectomy cavities in 15 consecutive patients 

were evaluated by 4 clinical oncologists. Physicians had access to all clinical, 

imaging and pathology details. Independently, each physician assigned 

a cavity visualization score (CVS 1, cavity not visualized; 2, cavity visualized 

but margins indistinct; 3, cavity visualized with some distinct margins; 

4, cavity visualized with all but one margin distinct; and 5, all cavity margins 

clearly defined). Cavities were contoured and a margin of 1.5cm added, excluding 

lung, to define the planning target volume (PTV). The PTV maximum 

diameter in 3 axes, and geometric centres were calculated for each case. 

Standard deviation of the PTV and the average shift of co-ordinates of the 

centre of mass (COM) were used as measures of variability of the PTV. Conformity 

index (CI) was calculated between each observer-observer pair. This 

is the ratio of overlapping volume to encompassing delineated volume. CI of 

1 indicates 100% concordance, CI of 0.50 indicates that observers agreed on 

50% of the encompassing delineated volume and CI of 0 indicates no concordance. 

Cases with low CI were studied further to identify features associated 

with low concordance. 

Results: Median time from surgery to CT was 60 days (range 26-195). 3 

patients received neoadjuvant chemotherapy and 5 patients received adjuvant 

chemotherapy. The mean CVS assigned was 2.63, SD 1.24. Median 

PTV was 70.7 cm3 (range 20.2-213.5). The maximum differences in geometric 

COM coordinates (mean cm ± SD) were as follows: for medial-lateral 

2.35 ± 2.68, cranio-caudal 1.87 ± 2.04 and antero-posterior 1.39 ± 0.87. 

The mean CI was 0.38 (range 0 0.81) CI was < 0.50 in 56 of 90 pairings 

and 0 in 7 pairings. As the mean CVS ranged from only 1.5 3.5 it was not 

possible to correlate CVS with CI. Poor conformity index did not correlate with 

any patient or tumour characteristics, including long interval from surgery and 

administration of chemotherapy. 

Conclusions: Substantial interobserver differences in delineation of the postsurgical 

target volume have been demonstrated. CI of less than 0.50 was 

seen in 62% of pairings. The use of oncoplastic techniques in breast conservation 

surgery may contribute to the difficulty in localising cavities. Margins 

greater than 1.5 cm may be necessary for boost definition, if the cavity is not 

clearly visualized on CT. 

1113 poster 

INTRA- AND INTER-OBSERVER VARIABILITY OF INTERNAL 

TARGET VOLUME DELINEATION AND VOLUME CHANGES OF 

LUNG TUMOURS ON REPEATED CT SCANS 

A. Petoukhova 1 , T. Steyn 2 , Y. Kalidien 2 , E. Kouwenhoven 1 , P. de Haan 2 , 

R. Wiggenraad 2 , A. Verbeek-de Kanter 2 , P. van de Vaart 2 

1 

MEDICAL CENTRE THE HAGUE, Department of Clinical Physics, The 


2 

MEDICAL CENTRE THE HAGUE, Department of Radiation Oncology, The 


Purpose: To determine intra-observer and inter-observer variability of internal 

target volume (ITV) delineation of lung tumours. To determine changes 

in the ITV during stereotactic treatment taking inter-observer variability into 

account. 

Materials: Between 9/2007 and 1/2008 ten patients with stage I NSCLC were 

treated with stereotactic radiotherapy at our department. These patients were 

irradiated in 3 fractions of 20 Gy or in 5 fractions of 12 Gy. Multiple spiral 

CT scans (consisting of one full-range scan and six scans limited to the tumour 

region) were used to define the ITVs during free breathing respiration. 

For clinical use the ITVs of ten patients were delineated by the same experienced 

radiation oncologist (first observer) in the iPlan system (BrainLab). 

Intra-observer variability of this observer was determined based on three delineations 

of the same patient for four patients. To analyse inter-observer 

variability ITVs of all ten patients were additionally delineated by three other 

radiation oncologists. Moreover, the first series of CT scans performed before 

the treatment was followed by a second series of CT scans carried out 

approximately two weeks after the first series and after at least two irradiation 

fractions had been given. The ITVs of the first and second CT series 

were compared. A conformity index (CI) of two ITVs was defined as a ratio 

of the intersecting and the encompassing volume. Additionally to analyse 

inter-observer variability the ratio between the volume of each ITV and mean 

volume of all ITVs (ITV ratio) was introduced. 

Results: The mean intra-observer variability of ITV delineation for the first 

observer was 3.6% and 7.5% for the first and the second CT series, respectively. 

The mean standard deviation (for the ITV) of the inter-observer variation 

for the ten patients was 13.4% for the first CT series and 17.1% for the 

second CT series. For the first CT series the mean ITV ratios for the four 

observers (see Figure 1a) were 1.03, 1.08, 0.90 and 0.99, respectively. The 

corresponding mean CI was 0.74. For the second CT series the results were


comparable (ITV ratios 0.97, 1.15, 0.89 and 0.98, respectively, CI 0.73, see 

Figure 1b). On the 95% confidence level, there was no significant change of 

the ITV in the second versus the first CT series. However, on the 90% level, 

there was a significant increase in ITV for 4 out of 10 patients. 

Conclusions: Considerable intra- and inter-observer variability of ITV delineation 

of lung tumours was found. On the 95% confidence level, no significant 

change of the ITV during the course of treatment was observed. 

1114 poster 

INVESTIGATING THE IMPACT OF USING CT VS CT-MRI IMAGES 

DURING ORGAN DELINEATION AND TREATMENT PLANNING IN 

PROSTATE CANCER RADIOTHERAPY 

P. Karaiskos 1 , P. Mavroidis 2 , B. Costa Ferreira 3 , N. Papanikolaou 4 , P. 

Sandilos 5 , E. Koutsouveli 6 , C. Scarleas 7 , K. Dardoufas 5 

1 

UNIVERSITY OF ATHENS, Department of Medical Physics, Medical School, 


2 



3 

UNIVERSITY OF AVEIRO, I3N Physics, Aveiro, Portugal 

4 



5 

ARETEION UNIVERSITY HOSPITAL, Department of Radiology, Athens, 

Greece 

6 

HYGEIA HOSPITAL, Department of Radiosurgery and Medical Physics, 


7 

HYGEIA HOSPITAL, Department of Radiotherapy and Medical Physics, 


Purpose: Modern radiation modalities have the capability of producing highly 

conformal dose distributions. Given the steep dose fall-off characterizing 

these distributions, the knowledge of the tumor location and extension of the 

PTV becomes very critical. The purpose of this study is to investigate the impact 

of using combined CT and MRI images in organ delineation compared 

to using CT images alone. 

Materials: In this study, CT and MRI images were acquired for 11 prostate 

cancer patients, at the position of treatment. The CTV was delineated using 

the CT and MRI images separately. The bladder and rectum were delineated 

using the CT images. Fusion of the two image sets was performed using the 

mutual information algorithm. In this way the CTV drawn on the MRI images 

was transferred to the CT images. The PTV was produced by adding to the 

CTV 1 cm margin in all directions apart from that towards rectum, which was 

0.6 cm. So, for each patient 2 PTVs were produced (based on the CT and 

MRI images). Two 4-field 3D-CRT treatment plans were produced for each 

patient. The DVHs of the targets and organs at risk were calculated together 

with common dosimetric criteria. The individual treatment plans were compared 

using the biologically effective uniform dose (BEUD) together with the 

complication-free tumor control probability (P+). 

Results: At the optimum dose level of the average CT-based PTV dose distribution, 

the complication-free tumor control probability, P+ is 51.9% for a 

BEUDPTV of 87.0 Gy and for the average CT-MRI delineated PTV dose distribution 

it is 60.8% for a BEUDPTV of 88.0 Gy, respectively. The respective 

total control probabilities, PB are 83.1% and 85.4%, whereas the corresponding 

total complication probabilities, PI are 31.2% and 24.6%. According to 

these results, the expected clinical effectiveness of 3D-CRT treatment plans 

can be increased by a maximum ∆P+ of around 8% in the case where combined 

CT-MRI delineation of PTV is performed. 

Conclusions: Although the 3D conformal radiotherapy technique that was 

applied is not characterized by very high conformality, it is apparent that the 

better knowledge of the PTV extension improved considerably the produced 

dose distribution. The PTV is irradiated more homogeneously and rectum, 

which has the largest risk for complications, is spared better. In the figure it is 

shown that the complication probability of rectum is significantly lower in the 

CT-MRI based treatment plan. 

1115 poster 

KNOWLEDGE-BASED SEGMENTATION OF THE BODY CONTOUR, 

LOBES OF THE LUNG, SPINAL CORD AND HEART IN COMPUTER 

TOMOGRAPHY 

A. Stoll 1 , R. Bendl 2 

1 GERMAN CANCER RESEARCH CENTER, Department of Imaging and 

Radiooncology, Heidelberg, Germany 

2 UNIVERSITY OF HEILBRONN, Department of Medical Informatics, Heil- 

bronn, Germany 

Purpose: Segmentation of organs at risk for radiation therapy planning is 

a time-consuming and knowledge-intensive task. It cannot be repeated frequently, 

although it is desirable for modern radiation treatment. In this contribution 

a knowledge-based segmentation approach for automatic segmentation 

of organs at risk for radiation therapy planning is introduced. 

Materials: The architecture of the system comprises several components. 

First of all, a static knowledge base is part of the system. Static knowledge 

comprises all kind of knowledge that a treatment planner or physician has 

to involve while doing the segmentation on raw computer tomography image 

data. It is permanent valid and independent from individual anatomical conditions. 

Furthermore, a dynamic knowledge base is adapted to patient specific 

anatomical conditions. Dynamic knowledge emerges when a case arises. It is 

highly data-driven. Therefore, four methods of pattern recognition (k-nearest 

neighbor classification, perceptron, quadratic discriminant analysis and support 

vector machine) are evaluated to acquire patient specific knowledge from 

medical images. Given expertise, anatomical knowledge and medical metainformation, 

volume growing and random walk segmentation are initialized 

and applied without user-interaction. 

Results: The system is developed with twelve human patients and evaluated 

with five additional. The training data was separated into seven male 

and five female data sets to evaluate the classification performance. 909 

measurements for male data and 650 measurements for female data could 

be obtained from all transversal slices. One measurement includes six features. 

Five features are based on tissue frequency and one is an anatomical 

measure. K-nearest neighbor classification showed most true-positive classification 

results , but it is very time-consuming and computational intensive. 

Therefore, support vector machine classification, which is slightly worse in 

classification performance, is preferred. 

Conclusions: In conclusion, promising segmentation result could be 

achieved. Body contour and both lobes of the lung could be identified and 

delineated in nearly all cases. Segmentation of the spinal cord and heart 

showed to be more often unsuccessful. Therefore, robust configuration and 

segmentation algorithms are necessary. The implementation was able to deal 

with abnormality like obesity and status after lobectomy.

1116 poster 


MATCHING 2D CYSTOSCOPY WITH 3D CT TO IMPROVE BLADDER 

TUMOR DELINEATION: A FEASIBILITY STUDY 

H. Dees-Ribbers 1 , M. van Herk 1 , M. Hulshof 2 , A. Bel 2 , P. Remeijer 1 , F. 

Pos 1 



2 ACADEMIC MEDICAL CENTER, UNIVERSITY OF AMSTERDAM, Department 

of Radiation Oncology, Amsterdam, Netherlands 

Purpose: Main challenges in RT of bladder cancer are correct delineation of 

the tumor and localization during treatment. We routinely insert liquid radioopaque 

markers (lipiodol) around the tumor during cystoscopy. These markers 

are then used for both target volume delineation and image guidance. Our 

purpose is to further improve tumor delineation by combining cystoscopic images 

with the planning CT using a 2D-3D matching strategy based on these 

markers. 

Materials: For three patients with bladder cancer, lipiodol was injected during 

cystoscopy, followed by a planning CT scan. In an overview photograph, 

the marked locations were indicated. To register the overview image with the 

CT, corresponding markers were identified on the photograph and CT. In this 

preliminary work the assumption was made that the tumor was planar and 

that perspective distortion was small. The cystoscopy image was registered 

(affine) on the markers using in-house matching software that partly eliminates 

perspective distortion. The registration makes it possible to display 

the intersection of the CT-based delineation with the registered cystoscopy 

photograph. The final cost function (the RMS of the distances between corresponding 

markers) was used to quantify the quality of the registration. 

Results: An example of a registration between a cystoscopy image and a 

CT scan is shown in the upper part of the figure (dotted line). The intersection 

of the CT based delineation with the cystoscopy image is shown in the 

lower part of the figure. A clear mismatch is visible between the tumor shape 

on the photograph and the delineated one. The residual errors of the registrations 

were 0.15, 0.74 and 0.42 cm which is much smaller than the visual 

discrepancy between CT delineation and the tumor on cystoscopy. The major 

difficulty is, however, the identification of corresponding markers in CT and 

cystoscopy. 

Conclusions: Registration of cystoscopic images with a planning CT scan is 

feasible and is expected to improve tumor localization. Improvement of the 

matching method is needed however, first taking lens distortion into account, 

and second taking the curvature of the bladder surface into account, since a 

tumor is not planar. Furthermore the lipiodol injection protocol needs to be 

refined to make the identification of corresponding markers easier. Finally, 

software for delineation on fused cystoscopy and CT images needs to be 

developed. 

1117 poster 

S 355 

MAY MR DIFFUSION-WEIGHTED IMAGING AFFECT THE TREAT- 

MENT VOLUME OF HIGH GRADE GLIOMA? PRELIMINARY 

RESULTS OF A PROSPECTIVE TRIAL. 

M. Krengli 1 , D. Beldì 1 , L. Masini 1 , G. Loi 2 , A. Stecco 3 , A. Littera 3 , A. 

Carriero 3 

1 UNIVERSITY OF "PIEMONTE ORIENTALE", Radiotherapy, Novara, Italy 

2 HOSPITAL "MAGGIORE DELLA CARITÀ", Medical Physics, Novara, Italy 

3 UNIVERSITY OF "PIEMONTE ORIENTALE", Radiology, Novara, Italy 

Purpose: The present study analysed the role of MR diffusion-weighted (DW) 

imaging in the detection of treatment volumes for radiotherapy. Literature 

data show that MR DW images may be able to detect tumour infiltration into 

peritumoral edema and into normal-appearing white matter (WM) allowing to 

a better delineation of clinical target volume (CTV). 

Materials: Twelve patients affected by high-grade gliomas (WHO III-IV) operated 

and candidate to adiuvant chemo-radiotherapy have been enrolled thus 

far. Prior to radiotherapy, they underwent MRI study by MR DW imaging. The 

apparent diffusion coefficient (ADC) and the fractional anisotropy (FA) were 

analysed. ADCs and FA were measured on volumes of interest generated 

from isotropic DW images represented by the enhancing tumour, hyperintense 

regions adjacent to enhancing tumor and the normal-appearing WM 

adjacent to hyperintense regions. The same measurements were performed 

on simmetric locations in the contralateral hemisphere. 

Results: Mean ADCs values in enhancing tumour and in peritumoral hyperintense 

regions were increased compared with contralateral normal WM 

(828.16 mm2/sec vs. 588.33 mm2/sec and 984.3 vs. 545.5 mm2/sec). No 

difference was seen in mean ADCs between peritumoral normal-appearing 

WM and the corrisponding contralateral normal-appearing WM (547.5 vs. 

575.5 mm2/sec). No difference was appreciable in mean FA values between 

glioma regions and normal tissues. Mean FA values in peritumoral hyperintense 

regions were slightly decreased compared to contralateral WM (0.267 

vs. 0.395). 

Conclusions: Our data confirm the possible role of ADC in the detection of 

tumour infiltration in perilesional edema to be included in the CTV. ADC values 

do not give information on tumour infiltration into normal-appearing white 

matter (WM), but the limited number of observations does not allow to draw 

definitive conclusions. The role of FA value deserves further investigation.


1118 poster 

MRI DELINEATION OF POST-OPERATIVE TUMOUR BED IN PAR- 

TIAL BREAST & BOOST RADIOTHERAPY PLANNED IN PRONE 

POSITION: FUSION AND COMPARISON WITH CT/TITANIUM 

CLIP-BASED METHOD 

A. Kirby 1 , E. Scurr 2 , V. Morgan 2 , M. Schmidt 2 , H. Convery 1 , P. Evans 1 , 

N. deSouza 2 , J. R. Yarnold 1 

1 

ROYAL MARSDEN HOSPITAL, Academic Radiotherapy, London, United 

Kingdom 

2 

ROYAL MARSDEN HOSPITAL, Department of Clinical Magnetic Resonance, 


Purpose: A common method of tumour bed delineation for partial breast/ 

tumour bed boost radiotherapy involves outlining titanium clips & architectural 

abnormalities on CT images. Uncertainties remain regarding delineation of 

the tumour bed/normal tissue interface between clips. MRI offers greater softtissue 

resolution. This study compares fused MR/CT with CT/clips alone as 

methods of tumour bed delineation following wide local excision. 

Materials: At lumpectomy, 20 women with G1-2 invasive ductal carcinoma 

or DCIS of the breast each had 6-12 titanium clips placed in the four radial, 

the anterior & deep margins of excision. Each woman underwent a CTplanning 

scan and MRI in the same prone position. Three 3D-MRI datasets 

(T1-weighted (standard & fat-suppressed) & T2-weighted) were co-registered 

with the CT data and matched using multimodality skin markers & glandular 

breast architecture. Tumour bed (TB) was delineated on each of the CT and 

MR datasets separately, and on the fused MR-CT dataset. Clinical target 

volumes (CTV) were generated using a 15mm margin (limited by 5mm from 

skin and the chest wall/lung interface). Planning target volumes (PTV) were 

generated using a 10mm margin (limited by 5mm from skin). Concordance 

of CT with MRCT TB and PTV was quantified using a conformity index (CI) 

(ratio of overlapping volume to total delineated volume). The proportion of 

discordance attributable to CT or MRCT underlap was measured. RT was 

planned according to UK IMPORT LOW study criteria to cover at least 95% 

of the CT-clip defined CTV with >95% of the isocentre dose in each case. 

The percentage of the MRCT CTV receiving >95% of the isocentre dose was 

measured. 

Results: Following analysis of the first 7 patients, the mean CI for CT vs 

MRCT TB was 0.61 and for PTV 0.92. The mean percentage of total delineated 

TB volume not predicted by CT/clips (i.e. geographical miss of inflammation/seroma 

seen on MR) was 28.8%. The percentage of total TB not 

predicted by MRCT (i.e. inappropriate inclusion of normal breast tissue on 

CT) was 9.7%. The T1-fat-suppressed MR sequence most clearly demonstrated 

tumour bed and clips in 6/7 patients. Seroma was demonstrated on 

T2-weighted images in 4/7 patients. Partial breast RT fields covered a mean 

of 97.1% of the CT CTV and 96.8% of MRCT-CTV, each with 95% of the 

prescribed dose. Analysis of 20 patients’ data will be presented. 

Conclusions: The addition of post-operative MR to CT/clip data may increase 

the TB volume by identifying a larger volume of inflammatory tissue. 

CT may overestimate TB by failing to distinguish normal glandular tissue from 

inflammation. PTVs derived from fused MR-CT data are concordant with 

those based on CT/clip data alone. Treatment plans based on the CT CTV 

satisfactorily encompass the MRCT CTV in all cases so far. The addition of 

MR to CT/clip data may not offer worthwhile benefits. 

1119 poster 

OPTIMIZING PLANNING TARGET VOLUME FOR ADJUVANT 

RADIOTHERAPY IN STAGE I TESTICULAR SEMINOMA 

A. Magli 1 , M. Signor 1 , C. Foti 2 , S. Fongione 1 , E. Moretti 2 , M. R. Malisan 

2 , C. Sacco 3 , R. Padovani 2 , A. Buffoli 1 

1 AZIENDA OSPEDALIERO-UNIVERSITARIA, Radiation Oncology, Udine, Italy 

2 AZIENDA OSPEDALIERO-UNIVERSITARIA, Medical Physycs, Udine, Italy 

3 AZIENDA OSPEDALIERO-UNIVERSITARIA, Medical Oncology, Udine, Italy 

Purpose: At presentation, 75% of all seminoma of the testes have Stage I 

disease. As testicular seminoma is a model of a highly curable tumor, it is 

important that treatment is optimized to ensure maximal cure rates while minimizing 

long-term complications of therapy. The fact that radiation constitutes 

the primary postorchiectomy therapy for the majority of patients means that 

attention must be paid to the details of radiation, including the doses used 

and volumes to be irradiated, to optimize the therapeutic ratio. Adjuvant radiotherapy 

is currently standard treatment of Stage I seminoma (SOS). One 

large trial that mapped failures has shown that nearly half of all patients with 

infra-diaphragmatic relapses have recurrent disease within 1 cm of the field 

edge [1]. This suggests that better definition of the target volume may lead 

to improvements in radiotherapy results. Currently, radiotherapy is progressing 

into the era of computerised tomogram (CT) based planning rather than 

plain film planning. This offers the opportunity to determine what doses target 

structures are actually achieving, and to conform the delivery of radiation to 

the target structure volume. 

Materials: The TC dataset from 10 consecutive SOS patients were identified 

between june 2005 and march 2007 at the University General Hospital 

in Udine. Three had left sided and seven had right-side tumours. A supine 

position set-up was used: a head and neck support, the arms above the 

shoulders and the hands on the top of the head, a LEG FIX system for feet 

and knees immobilization. Patients were scanned from the lower chest to the 

obturator foramen, with intravenous contrast, using a slice thickness of 5 mm 

and slice gaps of 5 mm. The prescribed dose was 25.5 Gy in 15 fractions 

at ICRU point with 10 MV nominal photons beams. Two plans were generated 

for each of 10 patients: one using traditional rectangular para- aortic 

fields created using criteria from the Medical research Council [2] , and one 

using conformal fields generated based on vascular anatomy (aorta, inferior 

vena cava, ipsilateral renal vein) [3]. 3D-CRT treatments were planned with 

the following three beams: a) An anterior field (gantry angle 0 ◦ ) with a vertically 

oriented wedge (5 ◦ -20 ◦ ). b) Two anterior oblique wedged fields, set 

at gantry angles 285 ◦ -300 ◦ from the right, and 60 ◦ -70 ◦ from the left side, 

with wedge angles 52 ◦ -60 ◦ . All fields were individually MLC-shaped to conform 

to the PTV contour. The beam weights were set around 40% for the 

anterior field and around 30% for each of the lateral fields. Dose-volume histograms 

(DVH) were generated for both the traditional and CT-base plans. 

For each renal volume we recorded minimum, mean, and maximum dose, 

as well as V15 and V25. For the vessel and lymphnodes related volume we 

reporded minimum, mean, and maximum doses, as well as V25.5% (100% 

of prescribed dose), V24.225 (95%), V23.715 (93%) and D95 (as per ICRU 

5062 guidelines refs.) Follow-up on the recommendations of the guidelines 

on testicular cancer (UAE) 

Results: The dosimetric analysis of traditional plans showed that 

they provided reasonable dosimetric coverage of the PTV The TC 

based plan delivered improved dosimetry to the vessel PTV compared 

with the traditional field (CT D95=24,6Gy±0,1, Dmean=25.5Gy±0,2, 

V25.5=44%±13.9, V24.225=98.4%±0.8, V23.715=99,6%±0.2; traditional 

plans D95=19Gy±5.4, Dmean=24.4Gy±0.6, V25.5=24.4%±15.9, 

V24.225=83.3%±5.9, V23.715=89.6%±4.7). CT-based plans were significantly 

wider than traditional plans (CT=11.9 cm, traditional=9.9 cm) The 

CT plan gives a higher mean dose to the kidneys; the V25 is higher, 

too, but only to 4% of the total kidneys volume (CT Dmean = 10.1Gy±1, 

V15 = 21.1%±5.1, V25 = 4%±4; traditional Dmean = 5.1Gy±0.7, V15 = 

13.2%±2.5, V25 = 1.8%±2.2). The mean follow-up time was 20 months 

(range: 10-28 months), median 19 months. No local recurrence and late 

toxicity was observed in the studied population. 

Conclusions: A simple CT-based field generation algorithm for SOS provides 

improved dosimetry individualization. Higher renal V25 irradiation of a 

low volume is unlikely of clinical significance. Given the potential for improved 

disease control with relatively little additional effort and probably minimal patient 

morbility, it is reasonable to consider CT based planning when available 

for treatment of the SOS

1120 poster 


OUR EXPERIENCE USING A PET/TC HYBRID IN SIMULATION 

THERAPY 

A. Vila 1 , C. Trampal 2 , A. Sanchez-Reyes 3 , C. Lainez 1 , L. Pla 2 , A. B. 

Rodriguez Garcia 4 , A. Pedro 3 

1 

HOSPITAL PLATO, Radioterapia, Barcelona, Spain 

2 

IAT- CRC MAR (IRBB), Department of Nuclear Medicine-PET-TC, 


3 

HOSPITAL PLATO, Unidad Radiofisica, Barcelona, Spain 

4 

HOSPITAL PLATO, Radiofisica, Barcelona, Spain 

Purpose: Nowadays curative approach recommends abandoning the concept 

of elective nodal irradiation. More detailed information than 3D reconstructed 

CT images in Virtual Simulation procedures is necessary to achieve 

this. It is possible to adapt PET/TC hybrids for simulation therapy procedures. 

FDG is the main employed tracer. The main questions are: How do I define 

tumoral edges in fused images?. What nodes should I regard as positive to 

irradiate and what techniques are of election?. How do we risk organ preservation 

in that new approaches in radiation therapy (RT)?. 

Materials: A group of 20 patients were simulated in a Discovery R○GE 

PET/TC hybrids (11 NSCLC, 4 oesophagus, 4 nasopharinx and 1 brain 

glioma studied with C-11 Methionine). PET/TC tumoral images and theirs 

SUV data (Standarized uptake value) were analysed. Parameters of attenuation 

and correction were derived from CT data. PET and TC series were 

fused in Eclipse R○Varian. To understand this fused images contrast threshold 

calculation employing vision tools in a source to background algorithms 

methodologies based on Nestle et al. were used. Contoured target volumes 

and risk organs based on TC vs. PET and irradiation therapy techniques 

were compared (lung V20 and V30, heart, spinal cord and in head and neck 

cancer: EORTC 0225 protocol). 

Results: Irradiation was indicated in 17 of 20 patients (85%): Radicals 

(82.3%): 7 NSCLC, 2 oesophageal cancers, 4 nasopharinx cancers and finally 

1 brain glioma (IMRT surgical bed). Three patients were out of radiotherapy 

intent (15%): 2 M1 and 1 oesophagus tumour sent to radical surgery. 

Non suspected changes in stage after PET/TC findings were shown in 8 patients 

(40%). False negative PET nodes: 3 cases and 3 patients show < 1 

cm positive lymph nodes. The mean SUV maximum values was 13.3 gr/ml 

(range 3.1-20.2). Large SUV in advanced NSCLC cases. Target volumes 

based on PET shows generally less volume in cc. Preliminary results show 

that using PET vs. TC in target thoracic volumes preserved lung, heart and 

spinal cord with statistically differences. 

Conclusions: 1- PET/TC hybrids in simulation therapy is a significant advance 

in radiation therapy of some kind of tumours. 2- Images treatment and 

contouring in radiation therapy work station is preceptive. 3- Close liaison 

between Nuclear Medicine and Radiation Oncologists is necessary. 3- In our 

experience, source to background methodologies using PET images is an 

accurate method to chose adequate tumoral edge. 

1121 poster 

PARTIAL BREAST IRRADIATION WITH 3D-CONFORMAL- 

EXTERNAL-BEAM-RADIOTHERAPY TECHNIQUE (IRMA): A 

MULTICENTRIC DUMMY RUN WITHIN EMILIA ROMAGNA REGION 

G. Frezza 1 , A. Baldissera 1 , P. Chiovati 2 , F. Bertoni 3 , G. Tolento 3 , G. 

Guidi 4 

1 AUSL BOLOGNA BELLARIA, U.O. Radiotherapy , Bologna, Italy 

2 AUSL BOLOGNA BELLARIA, Medical Physics, Bologna, Italy 

3 POLICLINICO DI MODENA, U.O. Radiotherapy , Modena, Italy 

4 POLICLINICO DI MODENA, Medical Physics, Modena, Italy 

Purpose: Within Emilia Romagna Region (ER) a study protocol (IRMA) has 

recently been developed for pts. affected by breast cancer at low risk for 

local relapse who underwent conservative surgery. This study matches the 

results, in term of risk for local relapse and toxicity, of two breast irradiation 

techniques: Partial Breast Irradiation by 3D conformal external beam radiotherapy 

(PBI-3DCRT) and Standard Whole Breast Irradiation (WB). The draft 

of the protocol was sent to ER Radiotherapy Departments and then it was discussed 

in multidisciplinary sessions among oncologists, physicists and surgeons. 

At the end of this phase each Centre was asked to do a dummy run to 

evaluate applicability or problems about implementation of the protocol. The 

dummy run was proposed for PBI-3DCRT as it represents a new technique 

for partial breast irradiation. 

Materials: Clinical and CT set data of two pts. treated with conservative 

breast surgery were sent: one with a lesion in her right upper-central quadrant 

and another with a lesion in her left upper external quadrant. Surgical 

bed was delimited by clips. Oncologists were asked to contour and physicists 

to plan according the protocol. The protocol provides the contouring of GTV 

(clips). The GTV is isotropically expanded of 1.5 cm to obtain the CTV. This 

expansion is however limited towards skin and thoracic wall so that the distance 

between CTV and these structures is > 0.5 cm, excluding, where possibile, 

the pectoral muscle. Then a further margin of 1 cm is added to the CTV 

to obtain PTV. OARs provided by the protocol are: heart, homolateral lung, 

thyroid, contra- and homolateral breast (volume of breast tissue irradiated by 

S 357 

the standard WB tangential fields). It is provided by the protocol the possibility 

of obtaining plans with 4-5 non-coplanar fields using 6-10 MV photon 

beams in isocentric technique. The prescribed dose is 38.5 Gy delivered in 

10 fractions, according to ICRU criteria. The protocol provides the verification 

of the dose distribution to the eval-PTV, obtained eliminating from the PTV 

its part beyond pt. body and within 0.5 cm from the skin and thoracic wall. 

Protocol dose constraints are: - 90% of the prescribed dose covers >/=90% 

of the PTV eval and no points exceed 120% of the prescribed dose. - /=50% of the prescribed dose - 

Contralateral breast and Thyroid should receive < 3% of the prescribed dose 

to any point. -


relationship between cardiac dose distributions and radiation induced heart 

damage. 

1123 poster 

THE EFFECT OF TUMOR MOVEMENT IN THE TREATMENT OF 

LUNG CANCER PATIENTS- DYNAMIC MR BASED STUDY. 

A. Kovacs 1 , J. Hadjiev 1 , F. Lakosi 1 , G. Antal 1 , I. Repa 1 , P. Bogner 1 

1 UNIVERSITY OF KAPOSVAR, Department of Oncoradiology, Kaposvar, 

Hungary 

Purpose: In the modern radiotherapy of lung cancer breathing related tumor 

motion is a crucial question. Uncertainty resulting from tumor movement must 

be considered in 3D therapy planning especially in case of IMRT or stereotactic 

therapy. The purpose of our dynamic MR based study was to detect 

tumor movements in upper and mid lobe located lung tumors and to analyze 

motion effects on the treatment planning. 

Materials: Twenty-four patients with newly diagnosed stage II-IV lung cancer 

were enrolled into the study. According to tumor localization in the right S1- 

S3 segments 9, in the right S4-S6 segments 2, in the left S1-S3 segments 

9 and in the left S4-S6 segments 4 lesions were detected. In normal treatment 

position individual dynamic MR examinations were performed in axial, 

sagittal and coronal planes (100 slices/30 sec). To calculate the difference 

in position primary, the center of the tumor was marked in all slices . For all 

the tumors in all slices in all planes the coordinates of the tumor centers were 

registered. Totally 24x100x9=2,16x104 coordinates were collected, studied, 

and visualized, using E-RAD PACS software. 

Results: Movements of the tumor under normal breathing conditions were 

registered in the three main direction. The mean antero-posterior deviation 

was 0,109 cm (range: 0,063 cm-0,204 cm), the mean medio-lateral deviation 

was 0,114 cm (range: 0,06 cm- 0,244 cm). The greatest deviation was 

measured in cranio-caudal direction (mean: 0,27 cm, range: 0,079 cm- 0,815 

cm). The mean direction independent deviation was 0,18 cm (range: 0,09 

cm- 0,48 cm). 

Conclusions: Dynamic MR is a sensitive and well tolerable method for tumor 

motion monitoring for high precision 3D therapy planning in lung cancer. Our 

results demonstrate that tumors located in the upper and mid lobes have 

moderate breath synchron movements. 

1124 poster 

THE EVALUATION OF TUMOR MOTION AND TREATMENT ACCU- 

RACY IN LIVER TUMOR USING SYNCHRONY MOTION TRACKING 

SYSTEM (GENERATION 4 (G4) CYBERKNIFE) 

G. Kim 1 , S. Shim 1 , W. Chung 1 , C. Min 1 , J. Kim 1 

1 KONYANG UNIV.HOSPITAL, Radiation Oncology, Daejeon, Korea Republic 

of 

Purpose: The Synchrony motion tracking system records the breathing 

movements of a patient’s chest and combines that information with sequential 

x-ray pictures of inserted fiducials, to enable the a Generation 4 (G4) 

CyberKnife R○robot to precisely follow the moving tumor as it delivers each 

radiation beam. In this study, we evaluated the tumor motion and treatment 

accuracy of Synchrony motion tracking system for the treatment of liver tumor. 

Materials: We analyzed the motion of tumor during treatment in 64 treatments 

of 24 patients who received CyberKnife radiosurgery for liver tumor. 

All patients underwent ultrasonography-guided percutaneous placement of 

4-6 gold fiducials around the liver tumor before the recording of their planning 

CT studies. For each treatment, the gold fiducials are periodically identified 

in both X-ray images (two diagonal images) and used to compute the 3D target 

position at every beam during treatment. This information was converted 

to Mtsmain.log and got the value for the movement in each treatment. For 

the evaluation the treatment accuracy, we analyzed the correlation error (the 

distance between the model-based estimated and image-based actual positions). 

Results: For translational movement, the mean motion ranged 13.9±5.5 mm 

in superior/inferior (SI), 1.9±0.9 mm in left/right (LR), and 4.9±1.9 mm in anterior/posterior 

(AP). The vector of translational movement for the compensation 

of treatment was 5.3±3.6mm. For rotational movement, the mean motion 

ranged 2.6±1.3 ◦ in X (left/right) axis, 2.3±1.0 ◦ in Y(superior/inferior)axis, 

and 2.8±1.1 ◦ in Z (anterior/posterior) axis. The mean correlation error was 

1.1±0.7 mm. 

Conclusions: In this study, we could identify the rotational movement including 

translation movement of liver tumor during treatment. These data might 

be used usefully in treatment planning. Also, Synchrony motion tracking system 

has a clinically relevant accuracy in liver tumor 

1125 poster 

THE IMPACT OF PET-CT IMAGING IN RADIOTHERAPY PLANNING 

FOR ESOPHAGEAL CANCER 

A. Nishioka 1 , Y. Ogawa 1 , S. Kariya 1 , M. Tadokoro 1 , K. Nakatani 1 , K. 

Tsuzuki 1 , H. Ue 1 , N. Hamada 1 , K. Kubota 1 , M. Fukumoto 1 

1 KOCHI UNIVERSITY, Radiology, Nankoku, Japan 

Purpose: PET-CT is increasingly used in the clinical management of many 

cancers. Compared to existing diagnostic imaging modalities, the presence, 

location and extent of lesions may be more accurately ascertained with PET- 

CT. The present study examined the usefulness of PET-CT imaging in radiotherapy 

planning for esophageal cancer. 

Materials: Subjects comprised 10 patients (8 men, 2 women) with advanced 

or recurrent esophageal cancer in whom PET-CT was performed over a 6month 

period from April to September 2006 and for whom radiotherapy was 

planned using a 3-dimensional radiotherapy planning system (Pinnacle3). 

Mean age was 60.8 years (range, 49-86 years). Five patients had primary 

esophageal cancer, 4 patients had recurrent esophageal cancer and 1 patient 

underwent postoperative radiotherapy. First, in the above-mentioned subjects, 

CT was performed for radiotherapy planning (Hitachi, RADIX PRIMA) 

and the results were sent to a 3-dimensional radiotherapy planning system 

(Hitachi Medico, Pinnacle3). Next, diagnostic imaging findings besides PET- 

CT were examined, and Pinnacle3 was used to determine the extent of the 

primary lesion and the location and extent of regional lymph node and distal 

metastases. Based on PET-CT (GE, Discovery ST Elite) findings, the location 

and extent of the primary lesion, regional lymph nodes and distal metastases 

were corrected. Lastly, irradiation fields were defined based on corrected 

lesion location and extent, and the usefulness of PET-CT was investigated. 

Results: Besides 3 patients who only had distal metastases, the primary 

lesion was clearly depicted by PET-CT. As far as the extent of lesion progression 

was concerned, while ascertaining the extent of progression in the craniocaudal 

direction based solely on radiotherapy-planning CT scans is often 

difficult, PET-CT made this easy to ascertain. Regarding lymph node metastasis, 

PET-CT was useful in identifying all lesions, including small lesions that 

were difficult to detect by other methodologies. However, in 1 patient in whom 

surgery was performed after PET-CT, pathological examination showed lymph 

node metastasis, but PET-CT could not detect the lesion. 

Conclusions: PET-CT provided valuable information about gross tumor volume 

(GTV), and also detected unsuspected nodal disease. Therefore, if the 

limitations are clearly understood, PET-CT is very useful in radiotherapy planning 

for esophageal cancer. 

1126 poster 

THE ROLE OF 3D ULTRASOUND FOR DELINEATION AND DAILY 

LOCALIZATION OF THE SURGICAL BED IN PATIENTS UNDERGO- 

ING ADJUVANT RADIATION AND BOOST FOR LOCALIZED BREAST 

CANCER 

P. Wong 1 , T. Muanza 2 , E. Reynard 3 , T. Niazi 2 , B. Bahoric 2 , S. Faria 2 , 

K. Sultanem 2 

1 MCGILL UNIVERSITY, Radiation Oncology, Montreal, Canada 

2 JEWISH GENERAL HOSPITAL, Radiation Oncology, Montréal, Canada 

3 JEWISH GENERAL HOSPITAL, Medical Physics, Montréal, Canada 

Purpose: The objective of this study is to evaluate the feasibility of using a 3D 

ultrasound (US) image guided radiotherapy system to improve the accuracy 

of breast tumour bed (TB) delineation for planning and daily localization prior 

to breast irradiation techniques. 

Materials: A total of 15 breast cancer patients underwent imaging for this 

study. 3D-US images were acquired using The ClarityTM breast system 

(Resonant Medical, Montreal, QC). At simulation, a CT scan was acquired, 

immediately followed by a registered 3D-U/S scan. A second CT and US 

set was acquired prior to boost treatment, approximately 6 weeks apart. The 

TB’s were contoured independently on CT and US. The CT and US data sets 

were compared to quantitatively evaluate spatial and temporal differences between 

volumes acquired by CT and US. Furthermore, TB displacements and 

volume changes between CT’s and between US’s were investigated. Probe 

pressure at the patient skin was calculated. 

Results: The percent TB volume overlap was 80% (standard deviation=13%). 

US defined TB volumes were generally smaller, on average 44% 

(21%) than CT. The mean maximum extent of the US outside the CT contour 

was 0.3 (2.1) mm, 0.2 (2.3) mm and 0.1 (2.8) mm in the A/P, L/R and S/I directions 

respectively. The mean difference in centroid displacement between the 

simulation and boost, as detected by CT vs. US, were 0.4 (2.6) mm, 1.4 (4.7) 

mm and 0.9 (3.7) mm in the A/P, L/R and S/I directions. TB volume shrunk by 

5% (38%) on CT and 30% (34%) on US between scans, and the mean probe 

pressure at the skin was 3.2 (2.6) mm. 

Conclusions: In addition to changes in breast shape and day-to-day positioning, 

TB volumes and centroid locations change over time following breast 

conserving surgery due to tissue healing. These variations may reduce positioning 

accuracy and thus the efficacy of both radiation boost and partial 

breast irradiation (PBI) techniques. 3D-US volumes overlapped accurately 

with CT contours. It is capable of tracking tumor displacement over the course


of treatment. The probe pressure on the skin was minimal and likely did not 

influence the accuracy of US data acquisition. Intra-modality ultrasound IGRT 

potentially offers an accurate and non-ionizing solution for tracking the TB for 

PBI and boost on a daily basis. 

1127 poster 

THE UTILITY OF IMMEDIATE IMAGING USING A 64-MDCT IN 

TREATMENT PLANNING OF PATIENTS WITH HEAD AND NECK 

NEOPLASM 

M. Yamamoto 1 , H. Hirakawa 2 , K. Tanaka 3 

1 

KURE MEDICAL CENTER CHUGOKU CANCER CENTER, Radiation Oncology, 

Kure, Japan 

2 

KURE MEDICAL CENCER CHUGOKU CANCER CENTER, Department of 

Otolaryngology, Kure, Japan 

3 

KURE MEDICAL CENTER CHUGOKU CANCER CENTER, Department of Oral 

Surgery, Kure, Japan 

Purpose: The use of contrast media during treatment planning computed tomography 

(CT) scan offers much higher accuracy in delineating the gross tumor 

volume (GTV). We prospectively investigated and evaluated the utility of 

immediate and delayed imaging using a 64-multidetector computed tomography 

(MDCT) in treatment planning of patients with head and neck neoplasm. 

Materials: Between February 2007 and February 2008, 15 patients with 

squamous cell carcinoma of the head and neck received both unenhanced 

and contrast-enhanced CT scans. Following unenhanced scanning, a contrast 

bolus (100ml) was administered over 50 seconds and immediate imaging 

acquisition followed. One hundred seconds after completion of the bolus, 

a delayed imaging acquisition obtained. Tumor and normal tissue enhancement 

was calculated and analyzed using the paired t test. 

Results: Mean tumor enhancement in immediate and delayed imaging 

groups was 57.8 +/- 29.7 Hounsfield units (HU) and 54.4 +/- 24.0 HU (NS). 

Mean normal tissue enhancement in immediate and delayed imaging groups 

was 13.7 +/- 10.9 HU and 22.3 +/- 14.0 HU (P < 0.05). The mean difference 

between tumor and normal tissue enhancement in immediate and delayed 

imaging groups was 44.0 +/- 25.2 HU and 25.4 +/- 24.7 HU (P < 0.05). 

Conclusions: The immediate imaging groups resulted in a statistically significant 

increase the mean difference between tumor and normal tissue enhancement 

relative to delayed imaging groups. The immediate imaging technique 

used can offer much higher accuracy in delineating the GTV. 

1128 poster 

TUMOR MOTION MANAGEMENT IN THE CONFORMAL RA- 

DIOTHERAPY OF LUNG CANCER: INDIVIDUALIZED UNGATED 

MARGINS 

L. A. Perez Romasanta 1 , D. Pintado 1 , C. Carrascosa 2 , M. Sanz 1 , E. 

Lozano 1 , F. Mendicote 1 , A. Gil 2 

1 

HOSPITAL GENERAL DE CIUDAD REAL, Radiation Oncology, Ciudad Real, 

Spain 

2 

HOSPITAL GENERAL DE CIUDAD REAL, Radiophysics, Ciudad Real, Spain 

Purpose: Introduction and goals: Recent studies have shown that tumor 

motion can vary substantially among lung patients suggesting that individualized 

margins would likely be more appropriate than standard margins. We 

evaluate the benefit derived from the use of individualized (ungated) margins 

compared with treatment plans based on a population-based margins. 

Materials: Material and Methods: Treatment plans were based on CT images 

and single physician-contoured target volumes for 12 patients. Tumor 

motion data were acquired by 4D CT scans using RPM system (Varian) on a 

Lightspeed scanner (GE). 4D CT scans were used to generate the PTV-MIP 

(Planning Target Volume Maximal Intensity Projection = GTV-MIP + 1cm). 

Population-based margins were derived from the literature and were in use 

routinely at our institution (PTV-3D = GTV-3D + 2.0cm cc & 1.5cm ap and 

lat). CT series from mid-inspiration respiratory phase (3D series) were used 

to generate the PTV-3D. We compare target volumes and the percent volume 

of lung receiving at least 20 Gy (V20) for a standard prescription. 

Results: Results: PTV mean values were 289.8 cm3 and 587.4 cm3 for MIP 

and 3D series respectively. Mean PTV-MIP was 49.2% the mean PTV-3D 

volume. V20 mean values were 18.5% and 25.1% for MIP and 3D series 

respectively; mean V20 derived from MIP series was 24.9% smaller than V20 

derived from 3D series. Comparison with paired-T test resulted in significant 

differences (p ≤ 0,001) in PTV volumes and V20 values between MIP and 

3D series. 

Conclusions: Conclusions: Individualized ungated margins based on 4D 

MIP series result in reduced planning volumes and more favourable lung dose 

when compared with conventional 3D treatment planning, offering a potential 

benefit for patients with lung cancer. 

1129 poster 

S 359 

USEFULNESS OF FDG PET-CT IN THE RADIOTHERAPY TREAT- 

MENT PLANNING IN HEAD AND NECK CANCER 

I. Rodriguez 1 , A. Escribano 1 , B. Caballero 1 , L. Miralles 1 , M. J. Ruiz 1 , A. 

Garcia Grande 1 , A. Mañas 1 

1 LA PAZ UNIVERSITY HOSPITAL, Radiotherapy, Madrid, Spain 

Purpose: The combination of an anatomical and a functional image as the 

Positron Emission Tomography Computarized Tomography (PET-CT) has 

been of the utmost importance in the oncology field. Nowadays, aimed at 

achieving more precision in the gross tumor volume (GTV) outlining, interest 

in using it for radiotherapy treatment planning is rising.The objectives are 

to correlate head and neck cancer GTVs outlined with PET-CT, to compare 

them with CT through independent observers, and to identify patients with 

metastatic disease, for whom no radical intention treatment is indicated 

Materials: 14 patients with hypopharynx carcinoma and 5 with cavum carcinoma 

underwent radiotherapy treatment planning with FDG PET-CT. It was 

done in conditions of inmovilization and in each case 2 GTVs of the primary 

tumor were outlined. One observer used a PET-CT fussion and the other a 

CT; GTVs were compared and measured in cc at primary tumor level. 

Results: 2 patients were excluded for presenting distance disemination according 

to PET-CT. In hypopharynx tumor cases, the GTV outlined with FDG 

PET-CT was reduced by 30% compared to CT. In cavum tumor cases, reduction 

reached the 22% compared to CT. 

Conclusions: The usefulness of FDG PET-CT in malignant Head and Neck 

cancer is that it enables reduction of volume treatment due to its higher accuracy 

in the outlining of the GTV. Besides, it offers relevant information about 

the detection of distant metastasis. Consequently, the intention of the treatment 

might be modified. 

1130 poster 

VARIATION IN POSITION AND VOLUME OF ORGANS AT RISK 

D. Alsadius 1 , A. C. Waldenström 1 , N. Pettersson 2 , K. A. Johansson 3 , G. 

Steineck 4 , M. Müller 5 

1 


Department of Oncology and Clinical Cancer Epidemiology, Gothenburg, 

Sweden 

2 


Department of Radiophysics and Clinical Cancer Epidemiology, Gothenburg, 

Sweden 

3 


Radiophysicas, Gothenburg, Sweden 

4 

SAHLGRENSKA UNIVERSITY HOSPITAL, SAHLGRENSKA ACADEMY AND 

KAROLINSKA INSTUTET, KA, Department of Clinical Cancer Epidemiology, 

Gothenburg and Stockholm, Sweden 

5 


Radiology, Gothenburg, Sweden 

Purpose: Radiotherapy involves unwanted ionizing radiation to the organs 

surrounding the tumor. As part of a research program looking at the relation 

between dose volume and long-term side effects, we assessed the variation 

in position and volume of organs at risk in the small pelvis. 

Materials: The study included 17 patients, ten men and seven women. The 

organs delineated were the sigmoid, rectum, anal sphincter, bladder, penile 

bulb, and cavernous bodies. Comparing two CT scans for the same patient, 

we calculated the relative volume of each organ. Using the "smallest box" 

model, we measured the extreme points in the cranial, caudal, dexter, sinister, 

anterior, and posterior direction. 

Results: Concerning the sigmoid, we obtained good agreement in documented 

relative volume (smaller volume divided by larger volume >0.5, possible 

values 0.0 1.0) but large variation in the documented position anteriorly 

and cranially (overlap volume divided by maximum possible overlap greater 

>0.5, possible values 0.01.0). The anterior rectal wall varied in position increasingly 

in the cranial direction. The bladder showed good relative overlap, 

while the relative volume varied substantially. 

Conclusions: We implicate that, in efforts to diminish unwanted radiation 

during radiotherapy to tumors in the small pelvis, it is important to consider 

the variation in position and volume of the sigmoid, rectum, and bladder.


1131 poster 

VOLUME DETERMINATION UNCERTAINTY. QUANTIFICATION BY 

MEANS OF THE SPATIAL CUMULATIVE DISTRIBUTION FUNCTION. 

A. González-López 1 , R. Dávila-Fajardo 2 , F. López-Soler 2 

1 HOSPITAL UNIVERSITARIO VIRGEN DE LA ARRIXACA, Servicio de 

Radiofísica y Protección Radiológica, Murcia, Spain 


Oncologia Radioterapica, Murcia, Spain 

Purpose: Defining volumes in radiotherapy is one of the most important 

phases in treatment planning. It is related to uncertainties mainly due to different 

imaging modalities and observers subjectivity. Uncertainties also occur 

due to organs motion, daily positioning and treatment unit tolerances. In order 

to determine security margins to guarantee a suitable coverage those uncertainties 

must be quantified. For the evaluation of uncertainties related to the 

volumes determination different indexes can be used, most common of them 

are standard deviation and concordance index. They are obtained from the 

statistical analysis of a series of contours (samples) delimited by one or different 

observers in different moments. A good index must fulfil a set of aims. 

It must take into account the spread of the volumes as well as their spatial 

position, and should not show any functional dependence on the number of 

samples. The standard deviation does not accomplish the first statement 

while the concordance index fails the second one. The purpose of this work 

is to show the quantification of the volume uncertainties by means of the spatial 

cumulative distribution function (SCDF). The spatial distribution function 

is the 3D probability distribution function of the volume. To every point in the 

space it assigns the probability of being included in it. From this function we 

can get some common central and dispersion parameters as mean, median, 

standard deviation and the interquartilic range. 

Materials: The SCDF is obtained for the prostatic volume delimited from CT 

scan images. Three different observers draw prostatic volume for three patients. 

In one case 25 samples are obtained, for the other two cases the 

number of contours per patient is 6. The next step is to determine the frequency 

that every pixel appears in the contours. The SCDF is then obtained 

as the cumulative histogram of that distribution. 

Results: The GUI implemented for the analysis is presented in the figure. 

The volume obtained as the union of the different volumes is 63.2 cm 3 while 

the intersection volume is 36.9 cm 3 . The median volume is 53.1 cm 3 , and 

the interquartilic range is 14.5 cm 3 . If we assume a cubic dependence of the 

volume with the margin, this dispersion value corresponds to a margin of 1.1 

mm. 

Conclusions: The SCDF is a reliable method to asses the uncertainties associated 

to volume determination in RT planning. It possesses better characteristics 

that common indexes used for this purpose as the standard deviation 

and the concordance index.

Physics and technology : Adaptive 

and image/dose guided RT 

1132 poster 

EVALUATION OF AN IMAGE-GUIDED RADIATION THERAPY 

TECHNIQUE USED FOR PROSTATE CANCER WITH AN ON-BOARD 

IMAGER AND COMPARISON WITH AN ON-LINE ADAPTIVE RADIA- 

TION THERAPY TECHNIQUE 

M. Lindskog 1 , B. Sorcini 1 

1 KAROLINSKA UNIVERSITY HOSPITAL, Department of Hospital Physics, 


Purpose: The daily uncertainty concerning tumor localization is one of the 

major problems during the course of radiation therapy. Image-guided radiation 

therapy (IGRT) can be used to improve the localization and adjustment of 

the planning target volume. In the case of prostate cancer patients the interfractional 

movement of the target may be large due to changes in rectal and 

bladder filling. In 2004 a Varian linear accelerator with an integrated imaging 

system, a so called On-Board Imager R○(OBI) was installed at the Karolinska 

University Hospital. Since then prostate cancer patients have been treated 

with IGRT based on implanted gold markers. The aim of this work was to 

evaluate both this IGRT technique used for prostate cancer patients and an 

alternative on-line adaptive radiation therapy (ART) method with an On-Board 

Imager (OBI). 

Materials: The study involves one prostate cancer patient treated with the 

dose escalated image guided IMRT technique with a total dose of 78 Gy at 

2 Gy/fraction. At 6 different treatment fractions, within a time period of 16 

days, a CBCT image set of the pelvic region was acquired immediately after 

isocenter correction. Daily dose verifications based on the CBCT image sets 

were performed. To investigate if any improvements compared to the IGRT 

technique could be achieved with on-line reoptimization ART, a reoptimization 

of an IMRT plan on one selected CBCT image was performed. The risk 

of developing late rectal and bladder toxicity was quantified using normal tissue 

complication probability (NTCP) calculations. Additional measurements 

on an Alderson phantom were performed to verify the accuracy of using the 

CBCT images for dose calculations. 

Results: The phantom measurements showed small dose deviations between 

the CT and CBCT images, with a mean dose increase to the prostate 

and seminal vesicles (SV) on the CBCT image of 2.5%. The daily dose to 

the prostate and SV of the IMRT patient showed to be acceptable. The daily 

dose to the rectum did not exceed the prescribed rectal dose except at one 

treatment fraction and the highest risk of developing late rectal toxicity was 

about 10.4%. Large daily bladder dose variations were observed (see figure) 

and at two treatment fractions the bladder dose restrictions were exceeded. 

With a reoptimization process of the dose plan, the dose to the bladder could 

be reduced while the dose to the target could be slightly improved. 

Conclusions: This work shows that for this specific patient appropriate doses 

to the prostate and SV can be delivered with IGRT. However, introducing a 

suitable ART method could lead to a reduction of inter-fractional rectal and 

bladder dose variations. 

PHYSICS AND TECHNOLOGY : ADAPTIVE AND IMAGE/DOSE GUIDED RT 

1133 poster 

S 361 

4D TRACKING RADIOTHERAPY DMMLC-BASED DELIVERY FOR 

RESPIRATORY LUNG TUMOR 

Y. Liu 1 , B. Lin 1 , C. Shi 1 , S. Stathakis 1 , A. Gutierrez 1 , N. Papanikolaou 1 

1 UNIVERSITY OF TEXAS, CANCER THERAPY & RESEARCH CENTER, 

Radiation Oncology, San Antonio, USA 

Purpose: The aim of this study is to provide a pre-clinical evaluation of fourdimensional 

tracking radiation therapy to lung tumor using a prototype tracking 

system. The evaluation was based on films dosimetric analysis, time delay 

measurements and treatment planning DVH analysis by using two types 

of dynamic phantoms. 

Materials: The concept for four-dimensional tracking radiation therapy 

(4DTRT) can be shortly explained as to control the beam following the target 

motion. As the beam aperture is formed by using dynamic MLC, the 

challenging part for 4DTRT is how to move the MLC leaves to form a tracking 

beam according to the motion of target. The key component of the 4DTRT 

system was a prototype of TrackBeam. It consists of an image processing 

tools and a first-of-its-kind dual-layer micro MLC. DmMLC has two layers of 

orthogonal leaves which provide advantages in speed and conformality when 

forming beam aperture for tracking. The TrackBeam was mounted to a Varian 

Linac and connected to a workstation which process the online MV fluence 

and controls each leaf’s motion. A Quasar dynamic phantom was used for radiographic 

film irradiation with 4DTRT and also 3DCRT. The phantom has a 

Gafchromic film insert and a gold marker in the insert. It can move in Sinusoid 

mode as well as real patient respiratory cycle. A tissue-equivalent thorax dynamic 

phantom (CIRS R○) was used for DVH analysis after a phantom-based 

3DCRT planning and a 4DTRT planning developed respectively. 

Results: The synchronization of marker motion and the DmMLC leaf motion 

was achieved within less than 0.05 seconds. To evaluate the effect of realtime 

tumor tracking, three evaluation patterns, named as the Static (tumor 

without motion), 3DCRT (tumor in motion, static beam), and 4DTRT (tumor 

in motion, tracking beam), were studied with Gafchromic films in dynamic 

phantoms. The films analysis indicated that total 29.91% over the tolerance of 

5% and 5.09% of over the tolerance of 5% when the 3DCRT and 4DTRT films 

compared to a static film. The DVH comparisons indicate 4DTRT reduces 

significant dose to the Ring from 75% (80% volume) to 60% (50% volume). 

4DTRT also reduces considerable amount dose to the total lung from 33% 

(30% volume) to 22% (22%). 

Conclusions: We evaluated a 4D tracking delivery and provided dosimetric 

analysis based on radiographic films and DVH analysis of a 3DCRT and 

4DTRT planning based on dynamic phantoms. Lung tumors are susceptible 

to motion due to respiration. The objective of dose delivery is to provide full 

coverage to tumor as possible and meanwhile limit the dose to the normal 

tissue as possible.

S 362 PHYSICS AND TECHNOLOGY : ADAPTIVE AND IMAGE/DOSE GUIDED RT 

1134 poster 

A METHOD OF QUANTIFYING DEFORMATIONAL SETUP ERROR 

UNDER HEAD AND NECK IMMOBILIZATION IN PATIENTS UNDER- 

GOING IMRT USING CONE-BEAM CT. 

M. Wada 1 , M. Rolfo 1 , R. Height 1 , D. Lim Joon 1 , A. Rolfo 2 , T. Kron 3 , V. 

Khoo 4 

1 

AUSTIN HEALTH, Radiation Oncology, Melbourne, Australia 

2 

PETER MACCALLUM CENTRE, Department of Radiation Oncology, 


3 

PETER MACCALLUM CENTRE, Department of Medical Physics, Melbourne, 

Australia 

4 

ROYAL MARSDEN HOSPITAL, Radiation Oncology, London, United Kingdom 

Purpose: Precision radiotherapy of head and neck is achievable with conformal 

delivery techniques such as IMRT. High spatial fidelity of the irradiated 

structures at treatment delivery relative to the anatomical model created at 

simulation is of vital importance to minimise the potential dosimetric consequences 

of minor set up variation. With the ability to acquire 3D anatomical 

data for image guidance we are realising the complexity of set up variation 

even under strict immobilization in head and neck treatment. We can now 

observe variation in the position of the jaw, skull, various levels of cervical 

and upper thoracic spine and the shoulders in relation to one another. 3D 

verification techniques allow visualisation of such changes, raising questions 

of how these need to be dealt with. We present a simple method of quantitatively 

analysing the distortional set up error that occurs in head and neck 

patients undergoing a course of radical treatment 

Materials: 5 patients treated with IMRT/IGRT for primary mucosal SCC’s 

including daily CBCT were analyzed. Multiple local rigid co-registration of 

VOI were performed using an automated bone match algorithm using Elekta 

Xvi interface. The VOI’s included C1-4, C6-T2, clivus, symphysis menti and 

R/L lateral clavicle/coracoid process. The relative position of each VOI were 

quantified in x, y, and z planes. The difference in the relative positional coordinates 

to a reference point (C1-4) were interpreted as distortional anatomical 

change. Spatial data was entered into a Hotelling’s statistics programme 

based on the Newcastle model, to determine the systematic and random "distortional" 

variation. 

Results: Using the upper cervical spine as geometric point of reference, 

there seems to be very little distortional movement of the clivus. Relative 

positional discrepancy was within 2.0mm systematic +/- 1.8mm random in 

all directions. Larger relative movement in C6-T2 was seen especially in the 

antero-posterior and lateral directions with systematic / random discrepancy 

up to 9.5mm and 7.8mm respectively. A trend toward a systematic distortion 

in the infero-posterior vector was seen with symphysis menti, indicating relaxation 

of the jaw. Shoulders tended to migrate postero-inferiorly with a large 

random movement of up to 9.3mm in the cranio-caudal direction. 

Conclusions: Set up variation, including distortional movement (often seen 

but not quantified), could lead to significant difference between planned vs. 

delivered dose. The variability observed in the relative position of the VOI’s 

indicated there may be a pattern of distortional movement, which is able to be 

quantified with such method as presented. This in turn may assist in generating 

anisotropic margins for PTV and OAR, be used as an alert for adaptive 

re-planning and an objective assessment tool to benchmark immobilization 

strategies. 

1135 poster 

A NEW APPROACH TO CONTRAST ENHANCEMENT IN MAGICA 

GEL DOSIMETER IMAGE WITH MRI TECHNIQUE 

M. Shahriari 1 , M. Abtahi 1 , M. H. Zahmatkesh 2 , H. Khalafi 3 , S. Akhlaghpoor 

3 , S. Bagheri 3 

1 

SBU, Radiation Application Engineering, Tehran, Iran Islamic Republic of 

2 

NUCLEAR SCIENCE AND TECHNOLOGY RESEARCH INSTITUTE NSTRI, 

Tehran, Iran Islamic Republic of 

3 

NOVIN MEDICAL RADIATION INC., Tehran, Iran Islamic Republic of 

Purpose: Two major advantages of polymer gel dosimeters are their ability to 

determine integrated 3D dose distribution as well as their ability to form in different 

shape[1]. Always artifacts are major problems in medical imaging, and 

gel dosimeter MR images are not immune from these problems [2-4]. Since 

in gel dosimetery spatial resolution has a great importance, one should be 

careful in using image processing filters. In this study contrast enhancement 

of MAGICA gel dosimeters with MRI in water environment and noise in the 

dose map was investigated 

Materials: Gel ProductionIn this study a new type of gel dosimeter with 

acronym MAGICA was used. This type of gel dosimeter was manufactured 

by adding of agarose to the ingredient of MAGIC [5] gel dosimeter and MAG- 

ICA gel dosimeter was manufactured in Novin Radiation Medicine Institute 

(I.R.Iran) in 2004. Agaros and gelatin provide a gelling matrix and keep the 

monomers and polymers in 3D. Addition of agaros increases the strength of 

the gel and keeps 3D distribution of dose after irradiation.Always some free 

radicals are found in water that can initiate the polymerization reaction (self 

polymerization). Hydroquinone is used to band these free radicals and inhibits 

from self polymerization. Under irradiation and radicals are produced 

and initiate the polymerization reaction. IrradiationGels were irradiated with 

a clinical system (Terathron C) that irradiates 1.17 and 1.33 MeV gamma radiations. 

To create scattered radiation same as human body, the gels were 

put under 5 cm water in irradiation duration. The radiation field is and dose 

rate is . Gamma source was calibrated by ionization chamber.Imaging and 

preparing an R2 mapIn this study the proton magnetic properties variation 

was exhibited by magnetic resonance imaging (MRI). Gels were imaged using 

a 0.5T MRI system (Philips). Since the gel temperature during imaging 

increases up to , always a little motion artifact will exist in MR image [2]. 24 

h after irradiation one is sure that the polymerization mechanism would be 

completed.R2(=1/T2) maps were computed using modified radiotherapy gel 

dosimetery image processing software coded in MATLAB. 

Results: Since these experiments are performed in water environment, the 

effect of contrast enhancement in MAGICA gel dosimeter with MRI technique 

was investigated to achieve this good, MR images in water and air were acquired 

while all other conditions of imaging were the same, e.g. in both case 

container was fixed in the head coil and was left for few minutes to avoid motion 

artifact due to water disturbance in the container. Figure 1 illustrates the 

R2 map from imaging in water.With comparison to imaging in air environment, 

imaging in water environment has increased the contrast noticeably. When 

small phantom is used this contrast enhancement for real boundary of R2 

map determination is very important.Figure1- R2 map from imaging in waterR2 

map in each image was calculated with selection of regions of interest 

(ROI) with equal number of pixels and the mean values of R2 and standard 

deviation of R2 in those regions were calculated. In this study the number of 

pixels was 364 and the ROIS were selected in the center of the phantoms. 

Conclusions: Imaging in water environment R2 map contrast is enhanced 

noticeably. This contrast enhancement can referred to susceptibility artifact 

removing. Susceptibility artifact occurs as the result of microscopic gradients 

or variation in the magnetic field strength that occur near the interface of substance 

of different magnetic susceptibility. This gradient causes dephasing at 

the interface and signal loss. Since magnetic property of gel is very similar to 

water this artifact is reduced and contrast enhanced noticeably when imaging 

is performed in water environment.

1136 poster 

A PHANTOM BASED INVESTIGATION OF THE EFFECTS OF MIP 

VERSUS AIP DERIVED INTERNAL TARGET VOLUMES ON 4D 

TREATMENT PLANNING 

T. Roland 1 , P. Rassiah-Szegedi 2 , M. Szegedi 1 , P. Mavroidis 1 , N. 



2 UNIVERSITY OF UTAH, Physics, Utah, USA 

Purpose: To study the effect of MIP versus AIP derived internal target volumes 

in 4D treatment planning. 

Materials: A typical breathing cycle was programmed into the CIRS moving 

tissue equivalent lung phantom which contained a 2 cm diameter target. 4D 

CT data scans were acquired on the LightSpeed 4-slice CT (General Electric, 

WI). The Maximum intensity projection (MIP), and average intensity projection 

(AIP) were reconstructed from the 4D CT data based on 10 phases. In 

addition, the minimum intensity projection (MinIP) and two 3D helical scans 

were acquired (1) with the phantom moving and (2) with phantom static. The 

target on all image sets was contoured by a single person using a standardized 

window/level setting. Treatment plans were generated on Pinnacle 7.6 to 

study the effect of different electron densities (pixel value) at the tumor edge 

predicted by the different image sets. The same dose constraints and gantry 

angles were used to generate plans for all data sets. The dose and fluence 

grid was set to 3 x 3 x 3 mm3. The fluence maps for each gantry angle were 

compared. 

Results: The MIP derived internal target volumes (ITV) were largest. Both 

the MIP and the 3D static target produced similar relative intensity maps as 

shown in figure 1a and 1b where a more homogeneous fluence distribution 

is observed. The average variation of energy fluence from the center to the 

edge of the target was estimated to be 20% for the optimization based on 

the 3D static target, 27% for the MIP and 37% for the AIP case for the beam 

studied. The convolution/superposition algorithm/inhomogeneity correction 

inherent in Pinnacle is capable of predicting the lower dose at the lung/lesion 

interface when low electron density (Hounsfield unit) is detected. Since a 

minimum dose is prescribed to the lesion, the optimizer increases the photon 

fluence at the edge of the tumor in the AIP image set, where the electron 

density is lower compared to the MIP. 

Conclusions: Planning using MIP or AIP of a 4DCT plays a role in the final 

dose distribution delivered to the patient. Planning using the MIP will produce 

a more homogenous delivered dose to the lesion regardless of tumor location, 

whereas the AIP will deliver a higher dose to the lesion at the end of the tumor 

trajectory. 

1137 poster 

ACCURACY ASSESSMENT OF INTER-FRACTION DOSE ACCUMU- 

LATION USING NON-RIGID DEFORMATION MODELS: STUDY IN 

CUBIC SILICON PHANTOMS 

S. Fekkes 1 , W. van Elmpt 1 , J. Orban de Xivry 2 , G. Janssens 2 , P. Lambin 

1 , A. Dekker 1 



2 UNIVERSITÉ CATHOLIQUE DE LOUVAIN, Communications and Remote 

Sensing Laboratory (TELE), Louvain-la-Neuve, Belgium 

Purpose: In radiotherapy, inter-fraction dose accumulation is necessary to 

evaluate the dose distribution of an entire course of treatment by adding up 

the multiple dose distributions of the different fractions. This summation of 

dose distributions is difficult due to changes in tumour volume and possible 

changes in the patient anatomy during treatment. For this purpose, we have 

investigated the accuracy of a non-rigid deformation method in terms of dose 

accumulation. 


S 363 

Materials: CT images were acquired using our Siemens Oncor MV conebeam 

CT imager and dose calculations were performed on these CT scans 

using CMS XiO treatment planning system. In total, 5 arbitrary deformations 

with maximum displacements up to 3 cm were applied to a cubic silicon phantom 

with 27 implanted markers. Before registering the silicon was masked in 

order to erase the markers and force homogeneous density, the CT scans 

were registered to the CT scan of the phantom in non-deformed condition using 

’morphons’, a non-rigid deformation method. The calculated deformation 

field was applied to the dose distributions of the 5 CT scans, and the accumulated 

dose per voxel was calculated. Three different dose distributions were 

investigated; a simple 2 beam plan, a standard 3 beam conformal plans with 

wedges and a highly conformal 8 beam plan. To asses the accuracy of the 

non-rigid registration, the dose values at the 27 marker positions in the original 

CT images were taken as the reference dose values and compared to the 

dose values found with and without non-rigid deformation applied. 

Results: The maximum shift in marker position was 28 mm which lead to 

a maximum dose difference of 38%. The absolute dose difference due to 

deformation over all markers and CT scans for the 3 plans was 7.4±7.5%, 

8.1±6.6% and 6.3±9.4%, respectively. Using non-deformable registration 

a decrease of the absolute dose difference to 4.2±3.9%, 2.4±2.4%, and 

1.7±2.8% was achieved. Overall a significant (p


1139 poster 

ADAPTIVE RADIOTHERAPY PLANNING FOR CANCER OF THE 

OESOPHAGUS 

M. Hawkins 1 , C. Brooks 1 , A. Aitken 1 , V. Hansen 1 , D. Tait 1 

1 ROYAL MARSDEN HOSPITAL, Radiation Oncology, Sutton, United Kingdom 

Purpose: To investigate the potential for reduction in normal tissue irradiation 

using an off-line strategy; by creating a patient specific planning target 

volume (PTV) with cone beam CT (CBCT) imaging acquired in the 1st week 

of radiotherapy for patients receiving radical radiotherapy (RT). 

Materials: Patients receiving 30 fractions of 3D planned RT for locally advanced 

carcinoma of the oesophagus are investigated. CTV (tumour and 

nodes) is outlined on the CT. PTV is defined as CTV and oesophagus outlined 

3-5 cm cranio-caudally to which a 1.5 cm circumferential margin is added 

(clinical plan). Pre-treatment CBCT are acquired days 1 to 4 (week1), then 

weekly (2-6) for the duration of RT. The images are imported into the planning 

system. No correction for set-up error is made. The tumour (CTV1) and oesophagus 

for the length of the PTV are contoured on each CBCT and a 5mm 

margin is added circumferentially. A composite volume (PTV1) is created using 

week1 CBCT volumes. The same process is repeated using CBCT week 

2-6 (CTV2 and PTV 2). A new plan is created using PTV1 (adaptive plan). 

The coverage of the 95% isodose of PTV1 is evaluated on PTV2. Dose volumes 

histograms (DVH) for lungs (V20, V30); mean dose heart and max. 

cord dose for 2 plans are compared. 

Results: An average of 10 CBCT (range 8-12) for 8 cases were analysed. 

The CTV volumes were: CTV= 77±43 cc, CTV1= 86±48cc, CTV2= 

84±42cc. The changes in DVH are summarised in table 1. For the adaptive 

plan the coverage of the 95% prescription isodose for PTV1 was 97±2% and 

the PTV2 95.7±3%. (t test=0.1) 

Conclusions: A reduced planning volume can be constructed within the first 

week of treatment using CBCT images to account for set-up variation and 

target localization. A single plan modification can be performed within the 

2nd week of treatment with considerable reduction in organ at risk dose. 

1140 poster 

AN EFFICIENT METHOD FOR SCATTER CORRECTION IN 3-D 

IMAGE RECONSTRUCTION FROM MEGAVOLTAGE CONE BEAM 

PROJECTIONS 

K. Leszczynski 1 , W. Yao 1 

1 REGIONAL CANCER PROGRAM OF THE HÔPITAL RÉGIONAL DE SUDBURY 

REGIONAL HOSPITAL, Medical Physics, Sudbury, Canada 

Purpose: Scatter is a major problem in megavoltage imaging as it adversely 

affects the already poor contrast and, in volumetric reconstructions from 

cone-beam projections, it results in inaccuracies and artifacts. The purpose 

of this study is to develop an efficient method for scatter correction in 2-D 

projectional megavoltage x-ray images and to implement it in 3-D image reconstruction 

from cone-beam projections. 

Materials: The proposed scatter correction method is based on an approximation 

of the Klein-Nishina formula that describes first order x-ray Compton 

scatter. In the approximate scatter formula characterization of the scattering 

object is functionally separated from that of the imaging system. Using this 

formula scatter and primary x-ray fluences are estimated from projectional 

images in an iterative manner. The accuracy of scatter estimation is tested 

in comparisons with Monte Carlo simulations and on experimental phantom 

data. The additive version of the Algebraic Reconstruction Technique (AART) 

is used for 3-D reconstruction of phantom objects from megavoltage conebeam 

projections, acquired with a flat panel EPID on a linear accelerator. 

The effect of scatter correction on quality of tomographic reconstruction is 

evaluated. 

Results: The accuracy of scatter component estimates obtained with our approximate 

method, expressed as relative error with respect to the Monte Carlo 

simulation results, ranges from 2% to 3%, for simple geometry and anthropomorphic 

scattering objects, respectively. A significant improvement is noted 

in tomographic image reconstructions from scatter corrected cone-beam projections, 

particularly in terms of the improved accuracy of CT number (attenuation 

coefficient) values and contrast. Examples of reconstructions with and 

without correction for scatter are shown in Figure 1. 

Conclusions: The proposed approximate analytical method allows for highly 

accurate estimation of primary and first order scatter components in projectional 

x-ray images without the need for additional imaging time and dose to 

the patient. When applied to scatter correction in megavoltage cone beam 

CT it leads to marked improvements in the reconstructed volumetric images. 

The computational efficiency of the correction process makes it suitable for 

online applications, as it requires only a few seconds of processing time per 

projection image. 

1141 poster 

AN IMAGE GUIDANCE PROTOCOL FOR MOTION MANAGEMENT 

IN STEREOTACTIC RESPIRATORY GATED TREATMENT OF LIVER 

METASTASES. 

J. Cuijpers 1 , C. Haasbeek 1 , W. Verbakel 1 , B. Haring 1 , F. Lagerwaard 1 , 

S. Senan 1 , B. Slotman 1 

1 VU UNIVERSITY MEDICAL CENTRE, Radiation Oncology, Amsterdam, 

Netherlands 

Purpose: To demonstrate the clinical use and feasibility of the Varian 

OBI/CBCT system and MV-cine portal images for on-line verification of 

respiratory-gated treatment of liver metastases. 

Materials: In a patient with two liver metastases, three gold markers were implanted. 

Target volumes were delineated on a breath-hold MRI scan that was 

co-registered with the expiration phase of an audio-coached 4DCT scan using 

the markers. A 5 mm PTV margin was added to the GTV to account for set-up 

uncertainties and for residual motion of the tumour in the gating interval. A 

coplanar 9-field technique was used and a dose of 8 times 7.5 Gy was prescribed 

to the 80% isodose encompassing the PTV. Patient positioning was 

based on the Varian On-Board Imager (OBI) system using two gated orthogonal 

kV-images using the implanted markers. An expiration breathhold CBCT 

was made (with maximal 3 interruptions) to verify the relation between visible 

tumour and markers. Before start of treatment, fluoroscopy was performed to 

verify the treatment gate. The patient was treated using audio-coached respiratory 

gating at end-expiration using the Varian RPM system. During each 

beam, cine MV-images were taken to verify proper positioning of the markers. 

If a structural displacement of more than 3 mm was observed, the patient was 

repositioned. In addition, an off-line assessment of the MV-cine images using 

colour intensity projections was done to validate the adequacy of the GTV to 

PTV margin. 

Results: Although severe image artefacts caused by the gold markers limited 

the delineation accuracy on CT, the tumour could be visualized well on the 

co-registered MRI. Respiratory gating reduced the motion amplitude of the 

GTV from 20 mm to less than 2 mm, leading to a reduction of the PTV size 

from 93 cc to 58 cc. Visibility of the markers on the kV- and MV-cine images 

was excellent. MV-cine imaging revealed that the maximum deviation of the 

actual position of the markers relative to the planned position was less than 5 

mm during 95% of the beam gates. In less than 1% of the MV-cine frames a 

displacement up to 10 mm was observed. The treatment time per fraction was 

approximately 45 minutes and treatment was tolerated well by the patient. 

Conclusions: Audio-coached respiratory-gated stereotactic treatment of 

liver tumours at end expiration is a feasible and accurate way for treatment of 

liver tumours. Daily on-line set-up requires gated stereoscopic imaging based 

on implanted markers. MV-cine imaging provides an excellent way to verify

the treatment during and after each treatment fraction.This work was partially 

supported by Varian Medical Systems 

1142 poster 

APLAN: A 4D TREATMENT PLANNING EVALUATION PROGRAM. 

A. Bel 1 , D. van Rooijen 1 , M. Kamphuis 1 , R. Pool 1 

1 AMC, Radiotherapy, Amsterdam, Netherlands 

Purpose: The aim of this work is to develop a 4D planning evaluation program 

with realistic dosimetric calculations of geometrical deviations of target(s) and 

organ(s) at risk. 

Materials: A system "APLAN" was developed to recalculate 4D treatment 

plans, starting from "static" 3D (IMRT) plans. APLAN includes a parallelized 

and optimized version of PLATO’s dose engine (Nucletron, The Netherlands) 

and is running on a PC. The system has transparent access to the main relevant 

databases: that of the planning system (PLATO) and the Cone Beam 

CT (CBCT) (Elekta, UK). An arbitrary number of CT sets, acquired with e.g. 

repeated CT scans or daily Cone Beam CT, can be read into APLAN. On 

each CT set volumes of interest (VOIs) can be delineated. A complementary 

way of performing the 4D recalculation is to import geometrical deviations per 

VOI (translation and rotations), as acquired with for instance EPI or CBCT. 

In APLAN each CT-set might include a set of geometrical deviations. For a 

CT-set with geometrical deviations per VOI, the recalculation is done in a twostage 

process. First the complete CT-set is shifted, according to the corresponding 

deviation, and the dose is calculated. Secondly, the VOIs within the 

shifted CT-set are again shifted to obtain the corresponding dose. In this way, 

effects of moving outer contours (change of SSDs) is taken into account while 

the dose to VOIs is calculated by a dose shift. Ensuing dose calculations are 

presented as isodoses and DVHs of the dose per deviation, the total delivered 

dose per CT-set and the overall total dose. Performance of the system 

is evaluated in terms of speed and usability within the clinical environment. 

Results: The system is user-friendly; data from both the planning system 

and the CBCT can be accessed with a few mouseclicks. On a 4-core PC, 

dose calculation takes typically about 3.5 s per plan (5 IMRT beams) for each 

deviation. Until so far, the system is used in retrospective studies to evaluate 

the actually given dose, using available data on organ movements (prostate 

and bladder treatments). Inclusion of multiple CT-sets proved especially useful 

for a bladder study where the dose was delivered in two stages: a large 

elective area to treat lymph nodes and a boost IMRT-area for the tumor. Each 

plan involved different geometrical deviations that were easily accounted for 

by including two CT-sets. 

Conclusions: APLAN enables a clinically feasible way to evaluate consequences 

of organ movements during the course of treatment. 

1143 poster 

APPLICATION OF IMPLANTED SUTURE-TYPE MARKERS FOR 

POSITION VERIFICATION OF BREAST CANCER PATIENTS USING 

MV TREATMENT BEAMS 

M. van Os 1 , S. Quint 1 , J. W. Mens 1 , J. Penninkhof 1 , M. Dirkx 1 

1 ERASMUS MC-DANIEL DEN HOED, Radiation Oncology, Rotterdam, 

Netherlands 

Purpose: Introduction: In our clinic breast cancer patients with tumours 

smaller than 5 cm are usually treated with breast-conserving surgery combined 

with post-operative radiotherapy. For positioning verification and correction 

of the whole breast treatment with tangential beams the breast and 

lung contours that are visible in MV images are used. During the boost treatment 

on the tumour bed, position verification is generally not possible due to 

lack of useful contour information in the treatment fields. Because the clips 

marking the boost area are mostly not visible in MV images, they cannot be 

used as reference contour either. Presently a simultaneous integrated boost 

technique is replacing our sequential treatment technique for breast cancer 

patients, requiring 3D position verification of the tumour bed. In a previous 

study we demonstrated that this is possible by acquiring two orthogonal kV 

images in which the clips are visible. However, in our clinic kV imaging is at 

this moment only possible at two treatment units, while about 500 breast cancer 

patients are treated per year. Therefore a study was started to investigate 

whether position verification and correction of the tumour bed could also be 

performed based on gold markers implanted in the lumpectomy cavity using 

the MV treatment beams. 

Materials: Methods: Three suture-type markers (CIVCO Medical Solutions), 

gold spheres of 2 mm, were implanted in the lumpectomy cavity in patients 

undergoing primary breast surgery. During the course of treatment MV images 

of the boost fields and a pair of orthogonal kV beams were acquired at 

least twice a week. For each fraction, the 3D set-up error based on the markers 

was derived from both the MV and the kV images and their difference 

was quantified. In addition the stability of the markers during the course of 

treatment was investigated. 

Results: Results: The suture-type markers were very well visible on each 

of the MV images. In a planning CT, scatter artefacts due to the markers 

were similar compared to surgical clips. During the course of treatment the 


S 365 

position of the markers remained stable within 1 mm. Any loss of markers 

was not observed. Differences between the 3D set-up errors derived from 

the MV and kV images were within 1 mm on average. 

Conclusions: Conclusion: In contrast to surgical clips, suture-type markers 

are clearly visible in MV images of the treatment fields. Due to their stability 

they are well suited for position verification and correction of the lumpectomy 

cavity for all breast cancer patients. 

1144 poster 

CHARACTERISATION OF A LINAC CONE-BEAM-CT OPTION: WHAT 

IS THE FUTURE POTENTIAL FOR TREATMENT PLANNING? 

U. Gneveckow 1 , C. von Briel 1 , P. Cossmann 1 


Switzerland 

Purpose: For image-guided radiotherapy (IGRT) the different vendors of linear 

accelerators offer new kV imaging tools with Cone-Beam-CT functionality. 

The aim of this study was to evaluate the future potential of such a cone beam 

CT option for therapy planning purposes. 

Materials: With the Varian On-Board Imager (OBI) Cone Beam CT (CBCT) 

option in a single 360 ◦ rotation a volumetric CT data set with 14 cm scan 

length and a 25 or 45 cm field-of-view (FOV) can be acquired. In order to calibrate 

the system with regard to hounsfield units (HU) a special phantom has 

been designed to include the whole imager area. Instead of a standard electron 

density CT phantom consists of three attachable segments with identical 

dimensions in order to cover the whole scan range and to offer realistic scatter 

conditions. Removable inserts allow flexible positioning of the probes (in 

the center/middle/border of the FOV) in one of the three segments and the 

measurement of central axis doses. A planning study based on DVH analysis 

was carried out to determine the usability of CBCT data and compare 

these with diagnostic CT data. Therefore two typical treatment techniques a 

6-field prostate plan and a 3-field thorax plan have been evaluated using an 

humanoid phantom (RSD Alderson). 

Results: Comparisons of data between a diagnostic CT scanner and the 

3D-calibrated CBCT with regard to image quality and HU representation indicate 

good accordance. Within the field of view the HU variation is up to 5%. 

Towards the imager edges hounsfield units show small deviations relative 

to the imager center (max. 8%). Relative dose distributions in CBCT-based 

plans show minor differences to plans calculated using a diagnostic CT image 

dataset (p=0.002) and absolute dosage deviations are within 1% (p=0.001). 

Central axis doses applied during the acquisition of one volumetric data set 

are between 0.8 and 1.8 cGy depending on the geometry. Results with real 

patient data show good image quality. 

Conclusions: A properly calibrated CBCT option allows off-line treatment 

planning based on CBCT data. Dose distributions and absolute MU’s are 

almost equivalent to dosimetric calculations based on diagnostic CT data. 

Deviations observed are from a clinical point of view not relevant. The 

image quality is sufficient for contouring of target outlines. Furthermore CBCT 

can serve as control CT in order to adapt the target volume and resize the 

treatment fields and/or optimize the treatment plan. 

1145 poster 

CLINICAL DECISION CRITERIA FOR IDENTIFYING LUNG CANCER 

PATIENTS WHO DERIVE SIGNIFICANT BENEFIT FROM VARIOUS 

ADAPTIVE TREATMENT TECHNIQUES 

I. Land 1 , J. Mills 1 , K. Young 1 , O. Haas 2 , A. Wilson 1 

1 UNIVERSITY HOSPITALS COVENTRY AND WARWICKSHIRE NHS TRUST, 

Arden Cancer Center, Coventry, United Kingdom 

2 COVENTRY UNIVERSITY, Control Theory and Applications Centre, 


Purpose: To develop decision criteria for selecting the most appropriate treatment 

strategy between conformal radiotherapy (CRT), gating with or without 

breathing training and real-time tumour tracking for individual lung cancer patients 

based on respiratory traces obtained prior to treatment. 

Materials: A parameterised organ motion model describing the target coverage 

as a function of the duty cycle and treatment position is presented. Respiratory 

motion within the model is described by 319 breathing traces recorded 

for 24 lung cancer patients at several days under free-breathing (FB), with audio 

instructions (AI), and with audio-visual biofeedback (AV). For each trace 

the required internal margin size for CRT, tracking and gating was calculated 

to achieve a chosen target coverage. The optimal treatment strategy for an 

individual patient was based on the required margin size to cover the target 

at all sessions (M), the inter-fractional variation of M (SDm) and the standard 

deviation of the intra-fractional motion (SDintra). 

Results: Treating at exhale position resulted in a smaller M for a given duty 

cycle for 92% of the patients and a smaller SDm for 67% of the patients 

compared with treating at inhale position. For treating at exhalation there 

is no significant difference between the three breathing training techniques 

with regard to the required margin size. However, for treating at inhalation 

71% benefit from audio-visual biofeedback. A simplified view showing the


major steps involved in the treatment strategy decision process is given in 

Fig. 1. The limits for the margin size (Lm) and its inter-fractional variation 

(LSD) are based on radiobiological considerations. Assuming Lm=4mm and 

LSD=1.5mm, CRT would be selected for 50% of the patients. Gated treatment 

at exhale (inhale) position would be appropriate with FB for 12.5% (0%), 

AI for 4.2% (4.2%) and AV for 12.5% (12.5%). Finally, tracking for 20.8% 

(33.3%). For patients treated with gated RT either a constant gating window 

or an intra-fractional adapted window would be used depending on the magnitude 

of SDintra. 

Conclusions: The decision criteria presented indicate whether the tumour 

mobility of a patient justifies implementing adaptive treatment techniques and 

assist in deciding the most appropriate treatment strategy and parameters. 

Identifying the percentage of patients that would benefit from a particular 

treatment strategy also provides an indication of the equipment required in 

hospitals. 

1146 poster 

CLINICAL INVESTIGATION OF ANATOMICAL AND DOSIMETRIC 

CHANGES IN HEAD AND NECK PATIENTS USING CONE-BEAM CT. 

M. Olevik Dunder 1 , B. Sorcini 1 , A. Tilikidis 1 , C. Mercke 2 



Purpose: The purpose of this project was to investigate how a cone-beam 

computed tomographer (CBCT) in the treatment room as well as a conven- 

tional fan beam CT can be used to determine anatomical changes and their 

impact on dose distribution in head and neck patients. 

Materials: 4 head and neck patients were repeatedly imaged, apart from 

their planning CT, during the course of their radiation therapy. 1 patient was 

repeatedly imaged with a CT and 3 patients were repeatedly imaged online, 

using an On Board Imager (OBI) kV CBCT (Varian Medical Systems Inc., Palo 

alto, Ca, USA). CBCT/CT-series were aquired once to twice a week. Each 

CBCT/CT series was rigidly registered to the planning CT in the treatment 

planning system Eclipse (Varian Medical Systems Inc., Palo alto, Ca, USA), 

using bony landmarks, see figure. The planning target volume, spinal cord 

and parotid glands were copied to the current CBCT/CT series and, where 

needed, manually edited slicewise. The dose distribution from the treatment 

plan was viewed as of the current anatomy by applying the treatment plan 

to the CBCT/CT-series, i.e. creating a hybridplan, and studying the corresponding 

dose-volume histograms. NTCP (Xerostomia) was calculated for 

one critical organ as an example of another dose evaluation tool. Uncertainties 

in dose calculations using the CBCT were quantified by imaging an anthropomorphic 

phantom, i.e. constant anatomy, with different CBCT settings. 

A comparison was made between the quality of the CT and CBCT images 

with regard to evaluating dose distributions, as well as an assessment of the 

practicality of using the two different modalities. Skindose from imaging with 

the CBCT was estimated using TLDs. 

Results: The repeated 3D imaging shows anatomical changes clearly, however 

they were in these 4 patients only slight changes. The average dose 

deviation relative treatment plan in the patients’ targets was 3% and for spinalcords 

7%. The phantom imaging shows that using the CBCT corresponding 

dose deviations of up to 1% and 5% for target and spinal cord respectively 

can appear only due to difference in image quality, registration technique uncertainty 

and daily set up variations. 

Conclusions: The CBCT is a useful tool to view anatomic changes in patients 

and to get an estimate of their impact on dose distribution. 

1147 poster 

CLINICAL USE OF THE CONE BEAM CT FOR 3D IMAGE GUIDED 

GYN BRACHYTHERAPY 

B. Reniers 1 , F. Verhaegen 2 

1 MONTREAL GENERAL HOSPITAL, Medical Physics Unit, Montreal, Canada 

2 MONTREAL GENERAL HOSPITAL, MCGILL UNIVERSITY, Medical Physics 

Unit, Montreal, Canada 

Purpose: This paper focuses on HDR gynecological treatments using 

Fletcher or ring applicators. Our present standard is to use orthogonal images 

to reconstruct the 3D position of the applicator. The organs at risk are 

defined using the ICRU points. Our purpose is to introduce 3D planning using 

a novel cone beam CT (CBCT) scanner. 

Materials: The CBCT scanner Simulix Evolution (Nucletron), dedicated for 

brachytherapy in our department was used. This new tool allows us to obtain 

3D images in the treatment room prior to treatment. These 3D images are 

used to recalculate the actual dose delivered during the treatment using the 

Plato Brachytherapy Planning System (Nucletron). The first step was to optimize 

the image quality by modifying the acquisition protocol and some of the 

default parameters of the image acquisition. We can then compare the dose 

calculated with the orthogonal images and with the CBCT images

Results: The currently achieved image quality allows us to easily find and 

reconstruct the applicators and plan the cases. We are able to perform treatment 

planning calculation using the CBCT images and Plato (see figure). 

The first step was to enable us to reproduce the loading that was used for 

the actual treatment and to get the dose to the ICRU points and the point A. 

The positioning of points A is easily achieved. However, the position of ICRU 

points is more challenging. In our institute, they are positioned traditionally on 

the lateral film using the vaginal packing as a guide for the rectum point and 

the Foley balloon for the bladder. The packing is easily seen on the CBCT. 

The Foley balloon is filled with a 10% contrast solution prior to the CBCT. 

We can also in most cases draw organs at risk like the bladder or even the 

rectum using the rectal probe as a guide. This allowed us to identify cases 

where the real position of the rectum was moved by up to 2cm compared to 

the ICRU point. These cases would have required an asymmetric loading of 

the colpostats in order to reduce the dose to the rectum. It is however still 

impossible, as in the case of CT images, to use the CBCT images to draw the 

target without considering the introduction of other modalities such as MRI or 

Ultrasound. 

Conclusions: The planning for GYN from the CBCT images is feasible. 

CBCT presents the advantages over CT to be acquired in the treatment room 

and in the treatment position due to the larger clearance of the CBCT. It also 

allows reconstructing slices as thin as 1mm although in most cases, 2mm is 

a good enough resolution. It will allow us to better assess the dose to the 

organs at risk using dose-volume histograms and compare them to the ICRU 

points commonly used. 

1148 poster 

COMPARISON OF 2D-PLANAR AND 3D-VOLUMETRIC MATCHING 

FOR PATIENT SETUP VERIFICATION IN IMAGE-GUIDED IMRT OF 

HEAD AND NECK CANCER 

U. V. Elstrøm 1 , L. P. Muren 2 , J. B. Petersen 2 , C. Grau 3 

1 

AARHUS UNIVERSITY HOSPITAL, Department of Oncology Department of 

Medical Physics, Aarhus C, Denmark 

2 


C, Denmark 

3 

AARHUS UNIVERSITY HOSPITAL, Oncology, Aarhus C, Denmark 

Purpose: Volumetric imaging using linear accelerator based kV Cone-beam 

CT (CBCT) facilitates soft tissue and tumour volume visualization at the treatment 

session to reposition head and neck (H&N) cancer patients. This task 

has traditionally been based on bony landmarks utilizing the MV treatment 

beam and portal imaging, a feature also offered by the kV imaging system. 

This study aimed at determining differences in the setup uncertainty for H&N 

cancer patients obtained by three different techniques; 2D-planar MV imaging, 

2D-planar kV imaging and 3D-volumetric CBCT. 

Materials: 45 consecutive head and neck cancer patients treated with dynamic 

IMRT were enrolled. At the first treatment session and subsequently 

once per week, orthogonal MV and kV radiographs (A-P and lateral) were 

obtained together with a CBCT (Varian On-Board Imager TM ) of the patient in 

the treatment position. For both modalities the radiographs were compared 

to reference DRR’s. A bony landmarks-based 2D-2D manual match was performed 

to determine the translational couch shifts in the A-P, L-R and S-I 

directions and the rotations around the L-R and A-P axes. Each CBCT was 

3D-3D auto-matched to the planning CT using the whole HU-range followed 

by manual correction using the soft tissue contrast. The deviations in all six 

degrees of freedom were estimated. All matching was conducted by one 

physicist using commercial clinical software. 

Results: Preliminary results from 15 patients with a median of 5 (range 1 to 

6) connected image sets per patient were analyzed. The average difference 

in translational shifts for 2D-planar imaging (EPID-OBI) was (A-R, L-R, S-I) 

(0.02 +/- 0.11, -0.05 +/- 0.07, 0.02 +/- 0.11)cm which corresponded to agreement 

within 0.2cm for 98%, 100% and 95% of the matches in the respec- 


S 367 

tive directions. The rotational shifts agreed within 3 o for 98% of the cases. 

Comparing 2D vs. 3D kV imaging (OBI-CBCT) we found a small average difference 

in shifts but an increased standard deviation (0.03 +/- 0.13, 0.00 +/- 

0.18, 0.04 +/- 0.17)cm. The largest differences were observed in two patients 

with substantial tumour shrinkage. 

Conclusions: No statistically significant difference was observed between 

the match results from the three techniques and similar systematic and random 

errors were found. However, the larger deviations between 2D and 3D 

imaging were consistently observed in patients with considerable anatomical 

changes which illustrate the potential of soft tissue visualization for target 

localization in IMRT of H&N cancer. 

1149 poster 

COMPARISON OF CONE BEAM CT AND CONVENTIONAL CT FOR 

CONTROL OF POSITION REPRODUCIBILITY IN STEREOTACTIC 

RADIOTHERAPY 

E. Wåhlin 1 , I. Lax 1 



Purpose: As part of our method for stereotactic body radiotherapy (SBRT), 

a computed tomography (CT) scan is routinely acquired shortly before the 

first treatment occasion. This CT-image is matched to the CT-image used for 

treatment planning, in order to verify positioning reproducibility of the tumour 

in the stereotactic system. We have made a preliminary investigation in order 

to evaluate the possibility of using cone beam CT (CBCT) for this positioning 

verification. 

Materials: For a limited number of patients undergoing SBRT at our department, 

CBCT scans were acquired after set-up for the first treatment fraction. 

The CBCT image and the images from the conventional verification CT were 

each registered independently to the treatment planning CT. The registration 

was performed using the fiducial markers of the stereotactic body frame. Images 

from the two CT modalities were compared for each patient with respect 

to their capability of visualising relevant structures, the tumour as well as bony 

structures and other organs. Also the two registrations for each patient were 

compared geometrically to investigate how well they correlated with the treatment 

planning CT. 

Results: Image quality is less good in CBCT images than in conventional 

CT, much due to streak artefacts. Tumours in the lung are still clearly visible 

in CBCT images, whereas tumours in e.g. the liver can not be distinguished 

from the surrounding healthy tissue. Both the CBCT and the conventional CT 

agree well with the treatment planning CT; generally within a few millimetres. 

Conclusions: This preliminary study indicates that for treatments of tumours 

in the lung, CBCT can replace conventional CT for positioning verification. 

For tumours in other organs, where direct visualisation of the target is not 

possible with CBCT, a surrogate must be used such as adjacent organs, bone 

structures or radio-opaque markers. In these cases, the inferior image quality 

of CBCT is a disadvantage compared to conventional CT. 

1150 poster 

COMPARISON OF SETUP ERRORS MEASURED WITH THE KILO- 

VOLTAGE CONE-BEAM CT AND ELECTRONIC PORTAL-IMAGES 

FOR BREAST CANCER PATIENTS 

R. Topolnjak 1 , J. J. Sonke 1 , D. Minkema 1 , P. Remeijer 1 , C. Rasch 1 , C. 

van Vliet-Vroegindeweij 1 



Purpose: With the clinical introduction of cone-beam CT (CBCT) systems 

setup errors can be measured with high accuracy in 3D. This allows quantifying 

the performance of portal image registration techniques that are still 

widely used for setup correction protocols. The purpose of this study was to 

quantify the differences in setup error measured with the CBCT and electronic 

portal-image device (EPID) for breast cancer patients. 

Materials: Nineteen breast patients, treated in a supine position for 28 days, 

were analyzed. CBCT scans (7-11 per patient) were acquired for an offline 

shrinking action level (SAL) setup correction protocol (action level: 9/N mm, 

Nmax=3) using bony anatomy registrations of the ribs (CBCTSAL). The EPID 

images were obtained during the same treatment fraction as the CBCT scans 

from the opposing oblique treatment beams (EPIDSAL). The EPID images 

were manually registered to the DRRs using the rib structures in the 2D coordinate 

system of the EPID (U, V). The U direction is roughly perpendicular 

to the patient surface and V is parallel to the cranial-caudal direction. 

CBCT scans were automatically registered with the planning CT scans in the 

3D room coordinate system. For the analyses the CBCT registrations were 

transformed to the EPID coordinate system. Correlation coefficients (R 2 ) and 

linear regression analysis were performed on the CBCT versus EPID registrations. 

The mean (M), systematic (Σ), random (σ) setup error and corresponding 

margins were calculated for the measured CBCTSAL and retrospectively 

simulated No-correction, EPID’SAL and EPIDOnline protocols. The simulated 

protocols were calculated assuming that CBCT provided the true data.


EPID’SAL (corrected EPIDSAL) data was calculated by adding EPID measurement 

uncertainties (EPIDSAL- trend_LineEPID) to the CBCTSAL data. 

EPIDOnline setup errors were calculated by subtracting CBCTSAL data from 

EPIDSAL data. Margins were calculated for a perfect 3D conformal irradiation, 

not taking organ motion and delineation errors into account. 

Results: The R 2 between CBCTSAL and EPIDSAL registrations was 0.61 

(U) and 0.35 (V). The slopes of linear regression analysis were 0.78 (U) and 

0.52 (V). This implies that the EPID underestimated setup errors in the V 

direction more than in the U direction. Table 1 shows M, Σ, σ and margin 

sizes for all protocols. 

Conclusions: EPID registration underestimated the actual bony anatomy 

setup error in breast cancer patients. This was probably due to poor image 

quality and non-visible anatomical landmarks on the EPID images, and 

therefore technicians did not correct EPID registrations sufficiently. Using the 

EPID instead of the CBCT system increased the required margins for 2 mm in 

an offline mode. If the EPID is used for online position verification a minimum 

of 5 mm margin will be necessary to account for registration uncertainties. 

Since M is relatively small for all protocols, we conclude that it is safe to use 

EPID for setup corrections. 

1151 poster 

COMPASS - A NOVEL SOLUTION FOR ON-LINE DOSE VERIFICA- 

TION AND 3D DOSE RECONSTRUCTION 

K. Eilertsen 1 , T. Furre 1 , H. Lorentzen 1 , A. Olsson 2 , E. Bäckmann 2 , N. 

Borglund 2 

1 THE NORWEGIAN RADIUM HOSPITAL, Medical Physics, Oslo, Norway 

2 RAYSEARCH LABORATORIES, Stockholm, Sweden 

Purpose: The COMPASS (Continous Online Monitoring PAtient Safety System) 

(IBA dosimetry, Germany, RaySearch Laboratories, Sweden) system 

consists of a transmission detector (T2D) attached to the accessory tray 

holder of the treatment unit, and a sophisticated software component for 

photon fluence reconstruction and subsequent dose calculation. Furthermore, 

Compass contains a workspace that facilitates on-line comparison of 

expected (from treatment plan) and measured 2D fluence as well as 3D dose 

distributions. The aim of this work was to perform a pre-clinical test of the 

T2D response and fluence reconstruction accuracy, and the the Compass 

dose calculation accuracy. 

Materials: Tests were carried out on a Siemens and a Varian accelerator. A 

number of different standard and IMRT treatment plans for two different phantom 

geometries were employed: An antropomorphic phantom loaded with 

TLDs, and a phantom that consisted of a MatriXX detector (IBA dosimetry, 

Germany) placed between two 5 cm thick slabs of solid water. The T2D response 

measured during beam delivery was reconstructed by Compass into 

fluence maps, and subsequently used by Compass to calculate the phantom 

doses. Standard statistics and gamma analysis were then applied to compare 

the planned with the measured/reconstructed fluence and dose distributions, 

respectively. 

Results: For the Siemens machine, the planned and reconstructed fluence 

distributions agreed within ±2%. The average deviation between the 

measured (TLD) doses and the reconstructed (from the measured fluences) 

doses in the antropomorphic phantom was 1.4%, the range was [-2.7%, 

3.8%], whereas the gamma analysis for the 2D data showed acceptable 

agreement at 3%/3mm level. For the Varian machine larger discrepancies between 

predictions and measurements were observed which may be attributed 

to an inadequate fluence model in Compass for this machine. 

Conclusions: An important challenge that remains in the field of external 

beam radiotherapy is daily verification and/or determination of the dose distribution 

in the patient. If employed together with a Conebeam CT system that 

allows for a precise depiction of the actual patient geometry, the Compass 

solution appears to be a promising step in this direction. 

1152 poster 

CONE BEAM CT AT THE GHENT UNIVERSITY HOSPITAL : FIRST 

CLINICAL RESULTS AND EVALUATION OF THE SELECTED WORK- 

FLOW 

G. Pittomvils 1 , M. Coghe 1 , A. Impens 1 , S. Nechelput 1 , G. Boon 1 , G. De 

Meerleer 1 , T. Boterberg 1 , W. De Neve 1 

1 GHENT UNIVERSITY HOSPITAL, Department of Radiotherapy, Gent, 

Belgium 

Purpose: At Ghent University Hospital the Elekta Cone Beam CT is used 

on the Synergy platform for patient positioning prior to treatment. An action 

level of 2 mm for patient repositioning was selected in an adapted ’no action 

level’ protocol. As proposed in literature a weekly follow-up measurement 

technique was introduced. The amplitude of this action level has been evaluated 

by analysing the systematic errors using a specially developed phantom 

and by post processing the clinical data for different pathologies with different 

patient immobilising devices. 

Materials: First a test phantom was constructed to evaluate the repositioning 

precision. The geometrical precision of the overall treatment process is compared 

to the amplitude of the ’no action level’. For treating intracranial lesions, 

patients are immobilised using a 3-point Posicast fixation system. The average 

mean of the displacements, their standard deviation (Σ) and the group 

mean of the standard deviations (σ) give an estimation of the random and 

systematic errors. The limited organ movements and good fixation should 

result in averages closed to the phantom measurements. The results of the 

weekly follow-up are compared to the selected threshold. 

Results: For test phantom the displacements in LR, AP and CC direction 

remain below 2 mm for al investigated protocols. The 3D average displacements 

(AvD) registered during the four initial fractions for the intracranial lesions 

and head and neck patients were 1.1±1.2 mm and 1.1±0.6 mm. The 

applied displacements (ApD) were 1.0±1.1 mm and 1.0±0.6 mm. During 

follow up the threshold was never exceeded and the remaining average difference 

(RAD) was reduced respectively to 0.35±0.9 mm and to 0.8±0.6 

mm. The analysis of the follow up data resulted for both indications in a setup 

treatment margin of 3.5 mm (M=2.5Σ+0.7σ). For lung tumours an AvD 

of 2.7±7.4 mm was observed of which 2.4±5.3 mm is due to CC displacement. 

After correction the RAD is within 0.3±1.0 mm and the obtained set-up 

treatment margins were 5 mm for the LR-direction, 6 mm for the AP-direction 

and 9 mm for the SI-direction. The same analysis is done for the prostate 

treatments. The AvD is very small (1.3±0.8 mm) and the spreading on the 

AP-direction is the largest. If an adaptive NAL protocol should be selected 

the set-up treatment margins should be 7 mm in LR-direction, 5 mm in CCdirection 

and 11 mm in the AP-direction. 

Conclusions: The amplitude of the action level (2 mm) for the adapted NAL 

protocol was appropriate for our clinical treatment protocols. 

1153 poster 

CONE BEAM CT BASED IGRT OF PROSTATE CANCER: INFLUENCE 

OF THE REGION SELECTED FOR IMAGE REGISTRATION ON 

PATIENT POSITIONING 

F. Pohl 1 , M. Hipp 1 , M. Riepl 1 , O. Koelbl 1 , L. Bogner 1 , B. Dobler 1 

1 UNIVERSITY OF REGENSBURG, Department of Radiotherapy , Regensburg, 

Germany 

Purpose: The purpose of the study was to investigate the influence of the 

size of the region selected for image registration on patient positioning in 

cone beam CT based IGRT of prostate cancer. 

Materials: An Elekta SynergyS R○linac equipped with Hexapod R○table top 

and XVI R○cone beam CT (CBCT) was used for image guided radiation therapy 

of prostate cancer. Patients were setup on the treatment table in an individual 

BlueBAG TM Vacuum Cushion (Medical Intelligence) using room lasers. 

A CBCT volume image was acquired and registered with the treatment planning 

CT using different areas for image registration: The XVI software requests 

the user to set the region for image registration using a cuboid called 

clip box. In this study 3 different clip box sizes were used: a) only soft tissue 

inbetween the pelvis minor (meaning the prostate itself), b) extended to 

include parts of the femoral heads and surrounded parts of the pelvis minor, 

c) extended to enclose the total hip. Image registration was performed using 

a greyscale match. The required correction values were calculated in 6 degrees 

of freedom (3 translational, 3 rotational) using the XVI software. The 

correction values were evaluated for the 3 clip box sizes in 21 data sets to 

assess the influence of the size of the clip box on patient positioning. The accuracy 

of the positioning process with the XVI system has been determined 

by phantom measurements to be within 1mm in each direction. 

Results: The length of the 3-dimensional vector required for translational 

correction of the patient position according to the XVI system was 6.0 mm 

for size a) of the clip box, 5.0 mm for size b), and 4.9 mm for size c), averaged 

over all data sets. Mean and maximum values of the latero-medial (Tx), 

cranio-caudal (Ty), and ventro-dorsal (Tz) components of the translation and 

the rotational corrections around the latero-medial (Rx), cranio-caudal (Ry), 

and ventro-dorsal (Rz) axis are given in table 1. 

Conclusions: The size of the region selected for image registration had no 

significant influence on the translational correction values calculated by the 

XVI system. For the rotational correction around the latero-medial axis, however, 

a significant difference could be observed for the smallest size, which did 

not include any bony structures. This can be explained by the fact, that bony 

structures have a large influence on image registration even if a greyscale 

algorithm is used. A possible rotation of the prostate relative to the pelvis will 

therefore be detected only if bony anatomy is not included in the clip box.

1154 poster 

CONE BEAM CT IMAGING ANALYSIS OF DAILY VARIATIONS IN 

BLADDER VOLUME AND POSITION DURING RADIOTHERAPY FOR 

BLADDER CANCER 

D. Yee 1 , L. Ko 1 , M. Parliament 1 , S. Rathee 2 , B. Murray 2 

1 CROSS CANCER INSTITUTE, Radiation Oncology, Edmonton, Canada 

2 CROSS CANCER INSTITUTE, Medical Physics, Edmonton, Canada 

Purpose: The urinary bladder is a dynamic organ whose position and size 

may vary significantly depending on the extent of bladder filling. Interfractional 

changes in target volume position and size may pose technical challenges 

to accurate radiotherapy (RT) delivery for bladder cancer. The purpose of 

this study is to quantify daily variations in bladder size and position occuring 

during a multi-fraction course of RT for bladder cancer. 

Materials: Ten bladder cancer patients receiving at least 20 RT fractions 

underwent daily cone beam CT (CBCT) bladder imaging in the treatment position. 

Patients were all instructed to have an empty bladder for each radiation 

treatment. Bladder and PTV were defined on each CBCT image and 

compared with pre-RT planning volumes for: bladder centre of mass shifts 

in the X, Y, and Z coordinates, bladder and PTV position and size variance, 

bladder volume margin displacement in the superior, inferior, lateral, anterior 

and posterior directions, and common overlap and mutually exclusive regions 

occupied by planning and CBCT bladder and PTV volumes. 

Results: Bladder and PTV volumes defined on 134 CBCT images from five 

patients have been analyzed. Mean ratio of CBCT to planning CT bladder volume 

was 74.56% (SD 14.2%). Mean CBCT bladder volume outside the planning 

CT bladder volume was 33.04 cm3 (SD 38.3 cm3). Mean planning CT 

bladder volume outside of CBCT bladder volume was 60.42 cm3 (SD 20.34 

cm3). Mean ratio of CBCT to planning CT PTV was 80.64% (SD 10.8%). 

Mean CBCT PTV outside the planning CT PTV was 36.49 cm3 (SD 21.1 

cm3). Mean planning CT PTV outside the CBCT PTV was 126.62 cm3 (SD 

50.9). Average CBCT bladder volume outside the planning CT PTV was 2.11 

cm3 (SD 2.9 cm3). Mean bladder edge displacement was: superior -0.63 cm 

(SD 0.83 cm), inferior -0.55 cm (SD 0.93 cm), right lateral -0.78 cm (SD 0.54 

cm), left lateral -0.78 (SD 0.67 cm), anterior -1.09 cm (SD 0.96 cm), posterior 

-0.85 cm (SD 0.74 cm). CBCT bladder and PTV volumes significantly differed 

from their planning CT counterparts (p < 0.043). 

Conclusions: Significant variations in bladder and PTV volume, size and 

position occured in patients undergoing RT on this trial. 

1155 poster 

CT DEFORMABLE REGISTRATION APPLIED TO THE EVALUATION 

OF SPINAL CORD DOSE ON HEAD AND NECK PATIENTS 

M. S. B. Pontes 1 , M. Figueiredo 2 , P. Chinita 3 , N. Teixeira 4 

1 MEDICALCONSULT, Physics, Lisboa, Portugal 

2 INSTITUTO SUPERIOR TÉCNICO, IT-DEEC, Lisboa, Portugal 

3 CENTRO ONCOLÓGICO DR A NATÁLIA CHAVES, Clinical, Lisboa, Portugal 

4 ESCOLA SUPERIOR DE TECNOLOGIAS DA SAÚDE, Physics, Lisboa, 

Portugal 

Purpose: Head and Neck patients undergo great morphological changes 

during their treatment course, thus it is tremendously hard to keep up track of 

every point dose in the treated area during the entire treatment. Normal procedures 

for dose comparison between different CT exams, done with a time 

gap and with normal anatomical changes, are based on RT Plan reconstructions 

made on the most recent CT. Along with this action, and depending on 

the actual deformation of the vertebral column, one can never be confident on 

the supposed spinal cord reported dose. In the present work, we propose a 

new method for spinal cord dose registration, based on CT deformation using 

a 3D Thin Plate Spline (TPS) Model. 

Materials: The TPS is a very well known tool for image registration, based 

on landmarks, and an excellent and fast method for the scope of this work. In 

fact, TPS allows making small deformations in our ROI (cervical column and 

spinal cord), regardless of what happens on other parts of the body, and it 

can lead a perfect fit between anatomic landmarks (ex: spinous processes). 


S 369 

The first step of our method is the treatment dose calculation on the original 

CT. Afterwards a subsequent CT is introduced, previous RT fields are reconstructed 

and calculations repeated for latter comparison. Then the spinal 

cord is segmented from C1 to T2 and precise anatomical landmarks located 

on the vertebrae (~70 points) are selected on both scans. Subsequently, the 

TPS transformation map between the two CTs is calculated using the landmark 

coordinates, and is applied to the first calculated 3D dose map. The 

resulting dose map can be superimposed to the second CT and dose values 

in any spinal cord point or location are obtained. The programming part was 

done on MatLab R○and calculations on Eclipse R○. 

Results: Assessment of the accuracy of this method is done by comparing 

DVH parameters of the spinal cord. Patients were split in two groups: 3 patients 

treated with IMRT and 6 with conformal treatments. Spinal cord mean, 

standard deviation, and maximum dose were computed and compared between 

the original CT calculations and the deformed dose map on the following 

CT. Differences were minimal: mean values differed ~0,2Gy for conformal 

treatments and 0,3Gy form IMRT; standard deviation ~0,2Gy in conformal 

and 0,3Gy in IMRT; and maximum ~0,4Gy conformal and 0,8Gy IMRT. This 

has a better agreement then the traditional reconstructions which, in the worst 

cases, can originate differences in the order of 1Gy for the mean and 2,8Gy 

for the maximum dose. The time spent in the whole process was very small 

when compared to other 3D deformable registration methods and was in the 

order of 9 minutes, excluding the human interaction involved in the segmentation 

and landmark selection. 

Conclusions: This method allow us to retrieve spinal cord dose values in any 

posterior CT acquisition with better relation to the initial treatment planning 

than by simply reconstructing the RT Plan. 

1156 poster 

DAILY CONE-BEAM CT IMAGE GUIDANCE FOR SINGLE VOCAL 

CORD TARGETING 

S. Osman 1 , H. de Boer 1 , A. Gangsaas 1 , B. Heijmen 1 , P. Levendag 1 

1 ERASMUS MC- DANIEL DEN HOED CANCER CENTER, Radiotherapy, 


Purpose: We are developing a technique for highly focused, single vocal cord 

irradiation (SVCI) in early glottic carcinoma, aiming at voice preservation and 

potentially allow for re-irradiation. From 4D CT studies we have concluded 

that breathing motion is not a significant problem in SVCI (Osman et al, Rad 

Onc submitted). Here, we investigate a procedure for fast and accurate, daily 

patient re-positioning using kV-cone beam CT (CBCT). 

Materials: Ten patients, treated in standard thermoplastic masks, were imaged 

daily in 33 fractions with XVI (Elekta Synergy). The acquisition time of 1 

min yields CBCT scans that average out the (generally very small) breathing 

motions near the cords. As a clinically feasible and fast method for on-line 

corrections, we selected the grey value registration available in XVI software 

(grey level correlation ratio) with a clipbox around the well visible thyroid cartilage. 

After application of the thus derived corrections, residue displacements 

with respect to the planning CT scan were measured in three points, i.e. the 

front node of the thyroid cartilage and the centers of the left and right arytenoids. 

Although specifically indicative for the position of the vocal cords, 

these points are less suitable for quick and reliable identification in an on-line 

registration procedure. The residue displacements of the center of gravity of 

these points are reported below. For a subset of CBCT scans, the entire procedure 

was repeated 5 times to determine the influence of clipbox placement. 

Results: While before correction the systematic displacements of the vocal 

cords were as large as 1 ± 3 mm (population mean µ ± SD Σ), Table 1 

shows that daily CBCT registration and correction reduced these values to 

less than 0.3 ± 0.7 mm. Similarly, daily random positioning errors (SD σ) 

were reduced to less than 1 mm. Correcting for translations only and not 

for rotations did not significantly affect this accuracy. The residue random 

displacements partly stem from the small inaccuracies introduced by manual 

clipbox selection (SD = 0.30.5 mm). 

Conclusions: Using standard mask fixation and commercially available 

CBCT acquisition and registration software, daily on-line registration and correction 

to obtain sub-mm systematic and random displacements for the vocal 

cords is clinically feasible. Hence, the high targeting precision required for 

SVCI may be achieved.


1157 poster 

DEVELOPMENT AND EVALUATION OF A METHOD TO IMPROVE 

ACCURACY OF CONE BEAM CT TO MV ISOCENTRE IMAGE 

ALIGNMENT USING THE QUASAR PENTA-GUIDE PHANTOM. 

J. Sykes 1 , R. Lindsay 1 , D. Brettle 1 , D. Magee 2 , D. Thwaites 1 



2 UNIVERSITY OF LEEDS, School of Computing, Leeds, United Kingdom 

Purpose: The Elekta Synergy system is supplied with a ball bearing (BB) 

phantom and software tools which can be used to accurately check the alignment 

of Cone Beam CT (CBCT) images to the Megavoltage (MV) isocentre 

as part of a quality assurance scheme. The QUASAR Penta-Guide phantom 

provides an alternative method with the benefit of not being manufacturer specific. 

However, it lacks the accuracy and precision of the Elekta-BB method. 

To improve the accuracy we have developed a method utilising the essential 

elements of the method used by Elekta but with the Penta-Guide phantom. 

Materials: Eight portal images were acquired of the Penta-Guide phantom, 

aligned to the isocentre using room lasers. The images were acquired with 

opposing head angles (0 ◦ , 180 ◦ ) at each gantry angle (0 ◦ , 90 ◦ , 180 ◦ and 

270 ◦ ) and with a 12cm square field. Image processing software was developed, 

using Matlab, to automatically locate the centre of the central spherical 

air cavity in the Penta-Guide phantom and the radiation field centre from the 

field edges in the eight images. These were back-projected to determine the 

air-cavity position relative to the MV isocentre. A CBCT scan was performed 

and registered with a reference CT of the Penta-Guide phantom to determine 

the relative position of the air-cavity centre to CBCT image centre. The vector 

difference between these two measurements gave the CBCT-MV alignment. 

This procedure was repeated eight times and compared to eight measurements 

using the Elekta-BB method performed in the same session. 

Results: The systematic difference in CBCT-MV alignment between the 

two methods was 0.15mm, 0.02mm, and 0.09mm in the lateral, longitudinal 

and vertical directions respectively. The standard deviation of the difference 

from mean over all three directions was 0.09mm for the Elekta method and 

0.15mm for the Penta-Guide method. 

Conclusions: Our method of measuring the CBCT-MV alignment using the 

Penta-Guide phantom is highly accurate and reproducible while maintaining 

independence from the manufacturer. The method could potentially be employed 

on integrated kV-CBCT systems from any manufacturer. 

1158 poster 

DOSE CALCULATIONS ON MEGAVOLTAGE CONE-BEAM CT 

IMAGES FOR HEAD AND NECK CANCER PATIENTS WITH UNDE- 

TACHABLE METALLIC CROWNS OF TEETH 

K. Kagawa 1 , H. Yamaguchi 1 , H. Kizaki 1 , N. Wakai 1 , T. Imai 1 , I. Sumida 2 

1 NTT WEST OSAKA HOSPITAL, Radiation Oncology, Osaka, Japan 

2 OSAKA UNIVERSITY GRADUATE SCHOOL OF MEDICINE, Radiation 

Oncology, Osaka, Japan 

Purpose: To evaluate usefulness of megavoltage cone-beam CT images in 

dose calculations for head and neck cancer patients with undetachable metallic 

crowns of teeth. 

Materials: Kilovoltage CT (kVCT) and megavoltage cone-beam CT 

(MVCBCT) images were obtained for an electron density phantom (Gammex 

RMI467) by CT simulator (Siemens Emotion) and linear accelerator (Siemens 

ONCOR). Heterogeneity correction tables were generated and registered 

onto a treatment planning software (CMS XiO) for both kVCT and MVCBCT. 

Ten head and neck cancer patients with undetachable metallic crowns of teeth 

were retrospectively investigated. All patients were treated by standard kVCTbased 

plans. Each plan was imported to a MVCBCT study set and dose 

distributions were re-calculated. Dose calculation results were compared between 

kVCT and MVCBCT with special attention to the artifact areas on kVCT 

caused by metallic crowns of teeth. Dosimetry experiments were performed 

on a dental model with detachable metallic crowns of teeth to evaluate the 

accuracy of dose calculations on MVCBCT. Calculated and measured doses 

were compared between kVCT and MVCBCT with or without the detachable 

metallic crowns of teeth. 

Results: In phantom study, CT numbers of kVCT and MVCBCT were closest 

for water. As relative electron density increases, kVCT showed higher CT 

numbers than MVCBCT. In patient study, both false-high and false-low density 

areas were observed around metallic crowns of teeth on kVCT. These 

artifacts were hardly observed on MVCBCT. In these artifact areas, dose calculations 

on MVCBCT showed -23% to +15% doses compared with kVCT. In 

dosimetry experiments on a dental model, calculated and measured doses 

showed a good correspondence for kVCT and MVCBCT without the metallic 

crowns of teeth. With the metallic crowns, however, calculated doses on 

kVCT showed at most 56% difference from the measurement. The dose calculation 

error on MVCBCT remained within 5% even with the metallic crowns. 

Conclusions: It is possible to both underestimate and overestimate actual 

doses in the artifact areas caused by metallic crowns of teeth in standard 

kVCT-based planning. In such patients, MVCBCT-based dose calculations 

can give more accurate dose distributions and make a useful dose guide for 

daily treatment delivery. 

1159 poster 

DOSIMETRIC IMPACT AND THEORETICAL CLINICAL BENEFITS OF 

FIDUCIAL MARKERS FOR DOSE ESCALATED PROSTATE CANCER 

RADIATION TREATMENT 

I. Gauthier 1 , J. F. Carrier 2 , D. Béliveau-Nadeau 2 , D. Taussky 1 

1 

CHUM - HÔPITAL NOTRE-DAME, Department of Radiation Oncology, 

Montréal, Canada 

2 

CHUM - HÔPITAL NOTRE-DAME, Department of Radiation Physics, 

Montréal, Canada 

Purpose: To assess the impact of implanted fiducial markers (FM) and daily 

kilovoltage-imaging (kV-imaging) on dose-volume histograms (DVH) parameters 

and normal tissue complication probability (NTCP) for rectum and bladder 

during prostate cancer radiation treatment. 

Materials: Two different setup scenarios were compared for 20 patients 

treated with 3D-conformal radiotherapy (3D-CRT) for localized prostate cancer 

to a total dose of 76 Gy in 38 fractions: an hypothetical plan using planning 

target volume (PTV) margins associated with daily skin marks alignment 

combined with weekly portal imaging (traditional setup), and the actual treatment 

plan using FM and daily kV-imaging as image guidance. With traditional 

setup, PTV margins for the first 60 Gy were 1.5 cm in all directions 

except for 1.0 cm posteriorly. For the boost of 16 Gy, PTV margins were reduced 

to 1.0 cm except for 0.8 cm posteriorly. For the plan relying on FM 

and daily kV-imaging, margins were the same for the whole treatment length 

(1.0 cm in all directions except for 0.8 cm posteriorly). Various DVH parameters 

were compared including Radiation Therapy Oncology Group (RTOG) 

dose-volume constraints for rectum (V60 Gy ≤50%, V65 Gy ≤35%, V70 Gy 

≤25%, V75 Gy ≤15%) and bladder (V65 Gy ≤50%, V70 Gy ≤35%, V75 Gy 

≤25%, V80 Gy ≤15%). NTCP analysis was also performed using the Lyman 

model with equivalent uniform dose (EUD). 

Results: With traditional setup, 85% of patients had a V70 Gy >25% for 

rectum. With FM and daily kV-imaging, this proportion was lowered to 45%. 

Moreover, 30% of patients with traditional setup versus 5% with FM were not 

respecting at least three RTOG constraints for rectum. When relying on FM 

and daily kV-imaging instead of traditional setup, the rectum V60 Gy, V65 Gy, 

V70 Gy and V75 Gy were on average 4.5 to 6.9% less. For bladder, the V65 

Gy, V70 Gy and V75 Gy were on average 5.4 to 8.4 % less when treated with 

FM. The mean rectal and bladder dose was 4.7 Gy and 6.7 Gy less with FM, 

respectively. The mean rectal NTCP was 11.5% with traditional setup and 9% 

with FM. For bladder, mean NTCP was below 1% for both techniques. The 

rectal EUD reduction found when using implanted FM suggests that we could 

increase the prostate prescription dose by 2.1 Gy (to 78.1 Gy) on average, 

while keeping the same level of late rectal toxicities as with traditional setup. 

Conclusions: For men undergoing high-dose 3D-CRT for localized prostate 

cancer, PTV margins reduction allowed by FM and daily kV-imaging is an efficient 

way of lowering the proportion of patients not fulfilling RTOG rectal and 

bladder dose-volume constraints. NTCP analysis suggests that FM should 

decrease the rate of late rectal toxicities, or might allow for moderate dose 

escalation. 

1160 poster 

ESTIMATION OF CTV-TO-PTV MARGINS FOR PROSTATE AND 

HEAD AND NECK CANCER PATIENTS FROM SETUP VERIFICATION 

DATA WITH AN ON BOARD IMAGER 

M. Djordjevic 1 , B. Sorcini 1 



Purpose: To estimate minimum CTV-to-PTV margins for prostate and head 

and neck IMRT treatments from images acquired on-line with an On-Board 

Imager R○(OBI) prior to treatment delivery.

Materials: Anterior-posterior (AP) and right-left (RL) high quality radiographic 

images of 195 prostate cancer patients (6900 measurements) and 12 head 

and neck patients (368 measurements) were acquired with an OBI during 

course of treatment. 150 of the prostate patients were treated with IMRT and 

gold markers had been implanted in the prostate under transrectal ultrasound 

control. For these patients the target position was registered according to the 

implanted markers. On the other patients, automatic bone structure registration 

was performed. The deviation from reference images, at each treatment 

fraction, was recorded. For each group; the overall mean systematic error, 

the mean inter-fraction variation (σ) and the inter-patient variation (Σ) was 

calculated in each couch direction. To estimate a CTV-to-PTV margin, to ensure 

a minimum dose of 95 % to the CTV for 90 % of the patients, van Herk’s 

formula M = 2.5Σ + 0.7σ was used. The combined data for prostate patients 

with and without gold marker implants were compared to evaluate the additional 

margin needed to account for prostate motion relative bone structure. 

Results: The mean execution errors, σ, for the prostate patients based on 

gold marker implants were 2.76 mm, 2.12 mm and 2.02 mm and the preparation 

errors, Σ, were 4.48 mm, 2.10 mm and 3.76 mm in AP, RL and craniocaudal 

(CC) directions. The margin formula yielded PTV-margins of 13.1 mm, 

6.7 mm and 10.1 mm in AP, RL and CC directions. Margins needed to account 

only for patient setup error based on bone structures were 6.3 mm, 6.0 

mm and 6.7 mm in AP, RL and CC directions. For the head and neck patients 

PTV-margins of 4.8 mm, 4.2 mm and 6.9 mm were obtained in AP, RL 

and CC directions. The larger margin in the CC direction was due to a larger 

preparation error in that direction. σ was in the range 1.5 1.8 mm in the three 

couch directions. 

Conclusions: Our results indicate that almost twice as large PTV margin 

is needed in the AP direction as in the RL direction to account for motion 

of the prostate. For successful IMRT treatments of prostate cancer on-line 

target verification is necessary. With the use of seed implants and on-line 

OBI guidance the PTV margin can be reduced to 4-5 mm in all directions. 

The margin used at Karolinska Hospital for head and neck patients, 5 mm, 

is enough in the transverse directions, however our results indicate that a 

slightly larger margin seem to be needed in the CC direction. 

1161 poster 

ESTIMATION OF OPTIMAL INTERNAL MARGINS ACCOUNTING 

FOR RESPIRATORY MOTION AND TARGET LOCALIZATION USING 

A MODEL BASED SIMULATION 

O. Masataka 1 , H. Aoyama 2 , H. Uno 2 , S. Tahara 2 , K. Inamura 2 , M. 

Hiromoto 2 , M. Takemoto 3 , N. Katayama 3 , M. Kuroda 1 , S. Kanazawa 3 

1 OKAYAMA UNIVERSITY GRADUATE SCHOOL OF HEALTH SCIENCES, 

Department of Radiological Technology, Okayama, Japan 

2 OKAYAMA UNIVERSITY HOSPITAL, Radiology, Okayama, Japan 

3 OKAYAMA UNIVERSITY SCHOOL OF MEDICINE, Radiology, Okayama, 

Japan 

Purpose: Respiratory gating and respiratory depression are useful for respiratory 

motion in stereotactic body radiotherapy. There are many approaches 

to account for respiratory motion during radiotherapy using active breathing 

control, tracking tumor motion with markers, and so on. In conventional threedimensional 

conformal radiotherapy, a breathing motion margin is determined 

by free-breathing computed tomography scan. In such a situation, internal 

margins and localization for the target volume often have been determined by 

clinical experiences. The purpose of this study was to investigate the relationship 

of optimum internal margins between respiratory motion and localization 

of the target volume. 

Materials: A virtual square of dimension 512X512 matrices was created with 

the dimension of any FOVs(each pixel size was 1/8X1/8 mm 2 to 1/4X1/4 

mm 2 ) . A 2D sphere representing the tumor was placed inside the square. 

The motion of a 2D sphere was modeled by a simple cosine curve, and an 

approximated curve using a sinusoidal simulating respiratory motion. A minimal 

time interval(∆t=0.01 sec) and various motion parameters such as wave 

amplitude, radius of a target volume, and a function of motion were set. Then 

the probability densities of the target position in each parameters ware calculated. 

From the calculated data, the frequency of the coverage was determined 

by the range of motion, margins, and positions for the target volume, 

respectively. 

Results: The probability densities were simulated to represent of a tumor 

position with the various respiratory motion patterns. The frequency of the 

coverage was depended on the input function, wave amplitude and additional 

margins; especially, it decreased rapidly when the amplitude was greater than 

the radius of the target volume in small tumor. The approximate equation of 

optimal internal margins for target volume of 99% coverage was also determined. 

Conclusions: In this study, we’ve found some interesting patterns to predict 

optimal internal margins with respiratory motion for the target volume. This 

study also showed that a method of simulating for the moving target and 

visualizing probability density. Further work is in progress to evaluate the 

optimal margins for the target localization in these models. 


1162 poster 

S 371 

EVALUATION OF GEOMETRIC ACCURACY IN SETUP VERIFICA- 

TION WITH AN ON BOARD IMAGER 

M. Djordjevic 1 , B. Sorcini 1 

1 KAROLINSKA UNIVERSITY HOSPITAL, Dept of Hospital Physics, Stockholm, 

Sweden 

Purpose: Modern radiation techniques with highly conformal dose delivery 

require high precision in treatment setup. This study aims to evaluate the 

geometric accuracy of the available methods for setup verification with an On 

Board Imager R○(OBI) used in image guided radiation therapy (IGRT). 

Materials: Phantoms containing fiducial markers were used to investigate the 

geometric accuracy of the different protocols used in image registration with 

an OBI. Various translational and rotational phantom displacements were executed 

over a 4 month period in addition to several mechanical stability tests. 

Before each phantom displacement the image center agreement with treatment 

isocenter was measured. For each displacement kV-kV, MV-kV and 

cone-beam CT (CBCT) images were acquired to perform 2D and 3D registrations. 

The same kV image set was used with both 2D/2D Match (kV images 

DRRs) and Marker Match (kV imagesreference CT) applications. The stability 

and agreement of OBI center-of-rotation and reconstructed CBCT center 

with treatment isocenter was evaluated over the period. Further, 2D/2D and 

3D/3D (CBCT-CT) registration was compared on a group of ten prostate patients 

with implanted gold markers. 

Results: The phantom study revealed differences in geometric accuracy of 

the different protocols for setup verification. For rotational and large translational 

corrections the Marker match application showed more accurate and 

consistent results than 2D/2D match in fiducial marker registration. The accuracy 

of rotational corrections with Marker match was within 0.3 ◦ for rotations 

up to 10.0 ◦ . A mean transverse vector disagreement of 0.8 mm between OBI 

and treatment isocenters was observed. Further, a systematic disagreement 

between transverse kV image center and transversal CBCT origin influenced 

the relative outcome of 2D and 3D registrations. Disagreement in axial image 

center in kV and MV images affected the accuracy of MV kV image registration. 

Fiducial marker registration on prostate patients showed a statistically 

significant difference between 2D/2D and 3D/3D registration. 

Conclusions: Our results show that the OBI is a very stable tool in IGRT with 

accurate geometric reproducibility in both 2D and 3D image acquisition. We 

recommend automatic Marker match over 2D/2D match for prostate patients 

with seed implants when also correcting for rotation and in treatments with 

small geometric margins such as IMRT. When using 2D/2D verification we 

suggest that a kV-kV image set is used ahead of a MV-kV set as it is more 

time efficient, provide less radiation dose to the patient and the better image 

quality increase the reliability of the registration. In cases of large corrections 

an additional registration should be considered when using 2D/2D match. 

The time extent of a 3D/3D registration limits its use for daily setup verification. 

1163 poster 

HYPOFRACTIONATED STEREOTACTIC BODY RADIOTHERAPY 

FOR THORACIC LESIONS: A COMPARISON BETWEEN FRAME 

DRR-PV GUIDED AND FRAMELESS CONE BEAM GUIDED SET UP 

S. Ursino 1 , F. Fiorica 1 , S. Lappi 2 , S. Fabbri 2 , C. Flammia 2 , E. De 

Guglielmo 2 , L. Perazzini 2 , L. Vignoli 1 , F. Cartei 1 

1 UNIVERSITY HOSPITAL S.ANNA, Radiotherapy, Ferrara, Italy 

2 UNIVERSITY HOSPITAL S.ANNA, Radiation Physic, Ferrara, Italy 

Purpose: Hypofractionated Extracranial Stereotactic Radiotherapy (HSRT) 

uses high dose fraction delivered on small lesions preferentially located in 

parallel organs; treatment of lung lesions is really the main application of this 

technique. Tumor localization and patient immobilization is a key for high 

precision of treatment delivery. It is possible to obtain this using a dedicated 

bodyframe. The introduction in clinical practice of Cone Beam CT can be 

useful for target localization. The aim of our study is to compare the accuracy 

of treatment delivery using bodyframe or wing-board and vacuum pillow. 

Materials: In 2007 we analysed 12 patients (primary or secondary lung lesions) 

treated with HSRT ( 30-48 Gy in 3-4 fractions at 85% isodose line) and 

we compared frame and frameless set up verification for all patients and for 

al sessions. Six patients were treated using a bodyframe (Elekta Stereotactic 

Bodyframe System). The isocenter displacement in repositioning before each


fraction was evaluated using MV portal images aligning bones structures with 

DRRs. We analyzed set up translations in all three dimensions and applied 

online correction only for major set up errors (> 0.5 cm). Other six patients 

were treated using wing-board and vacuum pillow as immobilization devices. 

The localization of isocenter was obtained by CBCT acquisition before each 

fraction matching with CT plan. Set up displacements were always corrected 

on-line in all directions and a second CBCT was obtained to confirm the shifts. 

A verification of rotation for this set of patients was estimated by an independent 

software ( Syntegra Pinncle). Finally we analysed isocenter translations 

in all three axes, the absolute magnitude of isocenter dislocations, the shifts 

applied in CBCT group. 

Results: The isocenter translations in bodyframe treated patients were 1.4 ± 

1.4 mm, 1.3 ± 1.7 mm and 0.9 ± 1.8 mm respectively for lateral (X), anteriorposterior 

(Y) and caudocranial (Z) and the absolute magnitude of isocenter 

dislocation was 3.0 ± 1.5 mm. In the group of patients treated frameless 

an average shift of 0.6 ± 2.2 m, 2.7 ± 3.7 mm and 0.2 ± 1.0 mm was 

applied respectively for lateral (X), anteroposterior (Y) and caudocranial (Z) 

directions, the absolute magnitude of isocenter dislocation was 4.3 ± 2.5 mm. 

The average rotational corrected deviation around Y axis was 2.3 ± 4.6 ◦ . No 

detectable rotation around the X and Z axes was observed fusing CBCT with 

CT Plan. The second CBCT always confirmed the correct overlapping with 

the CT Plan after applying shifts. 

Conclusions: Our data seem to confirm that the accuracy of HSRT using 

bodyframe is comparable with framless treatment using CBCT. The high quality 

of CBCT imaging leads to correct set up error < 5 mm to obtain the same 

positioning of the planning CT. The use of wing-board and vacuum pillow as 

immobilization devices avoid large rotational errors which are difficult to correct. 

1164 poster 

IMAGE GUIDED SPINAL IMRT: CTV-PTV MARGINS INCLUDING 

INTRAFRACTION PATIENT MOVEMENT. 

R. Wiggenraad 1 , J. van Egmond 2 , J. van Santvoort 2 

1 MEDICAL CENTER HAAGLANDEN, Radiotherapy, The Hague, Netherlands 

2 MEDICAL CENTER HAAGLANDEN, Clinical Physics, The Hague, Nether- 

lands 

Purpose: Radiotherapy of spinal and paraspinal targets to doses higher than 

the tolerance dose of the spinal cord is possible with modern image guided 

techniques, combined with IMRT. As immobilisation of patients treated on 

these targets is not as effective as in cranial patients, consideration should 

be given to patient movement during the fraction. The purpose of this study 

is to quantify inter- and intrafraction movements in spinal patients and to establish 

CTV to PTV margins when these intrafraction movements are taken 

into account. 

Materials: Sixteen (para)spinal patients receiving fractionated high dose 

IMRT on the Novalis (Brainlab AG Germany) were studied using the Brainlab 

Exactrac system. Eight patients with targets in the cervical region were 

immoblised with a thermoplastic mask. The other patients were positioned 

as comfortably as possible on the treatment couch without immobilisation 

material. Before every fraction the positioning was checked and corrected. 

Position checks at the end of the fraction were done twice a week. For every 

patient the translation error of the positioning before and after treatment was 

calculated. We established the CTV-PTV margins for this group of patients 

by using random and systematic translation errors at the start and end of 

fractions in an extended version of the margin recipe of Stroom et al *. This 

extension also includes estimations of other inaccuracies. Rotational errors 

were not taken into account. 

Results: The total and median number of fractions given was 312 and 

25 (range 3-35), before all of which the position after setup-correction was 

checked. The total and median number of position checks after the fraction 

was 124 and eight (range 2-20). In the table the translation errors before 

treatment (after setup-correction) and after treatment are shown in millimetres. 

The use of immobilisation masks had no clear influence on these errors. 

The mean 3D vectors of the translation errors were 0.8mm before treatment 

and 1.5mm after treatment. Taking into account inter- and intrafraction positioning 

errors and other inaccuracies, we established as CTV- PTV margins 

for this group of patients: 2.2mm (anterior-posterior), 2.7mm (cranial- caudal) 

and 2.8mm (left- right). 

Conclusions: In (para)spinal image guided IMRT intrafraction movements 

are small in most patients. When these movements and other inaccuracies 

are taken into account CTV-PTV margins of 3mm are safe. *Stroom 

ea IJROBP 1999 43;4:905 

1165 poster 

IMAGE REGISTRATION OF HYPERPOLARIZED 3HE MRI AND 

X-RAY CT IMAGES OF THE LUNG VIA 1H MRI AND MUTUAL 

INFORMATION 

R. Ireland 1 , N. Woodhouse 2 , J. Swinscoe 3 , M. Hatton 3 , B. Foran 3 , J. 

Wild 2 

1 

UNIVERSITY OF SHEFFIELD, Academic Units of Radiology and Clinical 

Oncology, Sheffield, United Kingdom 

2 

UNIVERSITY OF SHEFFIELD, Academic Unit of Radiology, Sheffield, United 

Kingdom 

3 

UNIVERSITY OF SHEFFIELD, Academic Unit of Clinical Oncology, Sheffield, 


Purpose: For hyperpolarized helium-3 (3He) MRI to be used in lung cancer 

RT planning, 3He-MRI must be registered to the planning CT. A direct 

method of registering 3He-MRI to CT is to use anatomical control points. An 

alternative, semi-automatic method is via an intermediate 1H-MRI that can 

be registered to the CT using mutual information. The aim of this study was 

to compare these two methods. 

Materials: Eight NSCLC RT patients underwent 3He-MRI, 1H-MRI and CT. 

With patients in treatment position, 3D 3He-MRI was acquired during a breath 

hold of a 3He/ N2 mixture on a modified 1.5T whole body system using an 

elliptical birdcage coil. Axial half Fourier SSFSE breath hold 1H-MRI were 

also acquired. On the same day, a planning CT was acquired on a 16 slice 

CT during a 530ms deep inspiration breath hold performed with a 1L bag 

filled with room air that simulated the MRI breathing maneuvers. MR images 

were transferred to an RT planning system and CT image fusion was initially 

performed using anatomical landmark based rigid registration. Up to 8 

landmarks around the lung base, apex and carina on both CT and 3He-MR 

images were used. Secondly, the anatomical landmark method was used to 

register the 3He-MRI to the 1H-MRI and then mutual information was used 

to align the 1H-MRI and CT images. For both methods, registration accuracy 

was assessed using the relative volume overlap [1]. The consistency of the 

two registration methods was compared using the paired samples Student t 

test. 

Results: The mean±SD registration accuracy of 1H-MRI to CT was 

90.4±6.0%. Registration errors were most prominent at the lung base. Accuracy 

for the direct and indirect 3He-MRI to CT registration methods was 

82.1±4.2% v. 83.0±4.9%. A two tailed Student t test demonstrates that 

the difference of 0.9% is not statistically significant (p=0.22) therefore the two 

methods provide equivalent accuracy. 

Conclusions: This study demonstrates the feasibility of a semi-automatic, 

indirect method of rigid image registration of 3He-MRI to CT via mutual information 

of 1H-MRI to CT. Despite the intermediate registration, the indirect 

method provides a similar level of registration accuracy to a direct anatomical 

landmark only based method. This provides the first step towards the goal of 

fully automatic 3He-MRI to CT registration which may be possible if 3He-MRI 

and 1H-MRI can be acquired in parallel. 

1166 poster 

IMAGE-GUIDED HYPO-FRACTIONATED RADIATION THERAPY 

FOR PROSTATE CANCER: DOES US LOCALIZATION CORRELATES 

WITH GOLD SEEDS TRACKING? 

C. Fiandra 1 , F. Munoz 2 , R. Ragona 1 , A. Guarneri 2 , P. Franco 2 , P. 

Ciammella 1 , N. Rondi 2 , C. Iftode 1 , G. Cattari 1 , U. Ricardi 1 

1 UNIVERSITY OF TURIN, Radiation Oncology, Turin, Italy 

2 ASO S. GIOVANNI BATTISTA MOLINETTE, Radiation Oncology, Turin, Italy 

Purpose: Prostate cancer radiation therapy strongly benefits from high fields 

conformation to allow for dose escalation. Hence geometric uncertainties 

should be taken into account to optimize the treatment. Aim of this study 

is to compare a 3D US based image-guided verification system for prostate 

alignment during fractionated radiotherapy (US, RESTITU system, Resonant 

Medical Inc., Montreal) with the localization capabilities of a radio-opaque 

fiducial markers EPID based (GMs) imaging device 

Materials: A pilot study was then conducted wherein prostate displacements 

were measured in 5 patients undergoing daily EBRT for prostate cancer. For 

each patient, 3-mm slice thicknesses were obtained through the pelvis (and 

prostate) for CT simulation; contouring was performed using the Masterplan 

(Nucletron, The Netherlands) treatment planning system, and a nominal dose 

of 70.2 Gy in 26 fractions was prescribed corresponding to an EQD2 of 84,4 

Gy (α/β = 1.5 Gy). Patients were aligned daily using skin marks laser alignment. 

The US system resides in both the CT-Sim and treatment rooms and 

calculates prostate misalignment by comparing prostate 3D US images acquired 

at both planning and treatment session. Prostate localization was performed 

relying on markers position using a Matlab in house software; two MV 

radiographs, separated by a treatment angle of 90 ◦ , were then acquired and 

marker positions were digitized on both images. Shifts were subsequently 

calculated by each respective system (US and GMs) in the Latero-Lateral, 

Anterior-Posterior and Cranio-Caudal directions before each treatment fraction, 

previous to any couch adjustment or dose delivery. Daily positioning was 

recorded for both localization devices resulting in 107 paired measures; the

couch was then moved based on GMs shifts to execute the on-line correction 

Results: Figure 1 illustrates a scatter plot of matched pairs for the two localization 

systems and three orthogonal regression plots using the specified 

orthogonal variance fit ratio for each axis and vector; ellipses represent the 

95% confidence range of the distributions 

Conclusions: The 107 US/GMs paired statistical analysis shows a p-value 

(Wilcoxon signed-rank test) of 0.124 for LL, 0.643 for AP and < 0.01 for CC, 

which indicates that the difference between the two systems is statistically 

significant only for the CC direction. Therefore, the present study indicates 

that a significant systematic difference exists between US (Restitu) and markers 

based EPID methods only in the CC axis; this might be due to a reduced 

intrinsic US visibility in this direction. Further study is necessary to establish 

the relevance of different factors such as patients selection or inter-observer 

variability 

1167 poster 

IMAGE-GUIDED RADIOTHERAPY (IGRT) FOR PROSTATE CANCER: 

EFFECT OF RESIDUAL SET-UP ERRORS AND INTRA-FRACTIONAL 

MOTION ON PLANNING TARGET VOLUME (PTV) MARGINS. 

R. Benson 1 , Y. Rimmer 1 , S. Tudor 2 , J. Dean 1 , N. Muskett 1 , H. Patterson 

1 , S. Russell 1 , C. Woodward 1 , J. Fairfoul 2 , A. Doble 3 , N. Burnet 4 


2 ADDENBROOKE’S HOSPITAL, Medical Physics, Cambridge, United Kingdom 

3 ADDENBROOKE’S HOSPITAL, Urology, Cambridge, United Kingdom 

4 UNIVERSITY OF CAMBRIDGE, Oncology, Cambridge, United Kingdom 

Purpose: IGRT on-line correction techniques in prostate radiotherapy are 

often assumed to eradicate the systematic errors caused by set-up uncertainties 

and organ motion, � with PTV margins ≤ 3mm deemed adequate. The 

residual systematic ( ) and random (σ) errors that occur following prostate 

localisation or due to intrafractional motion are not routinely measured. This 

study analyses the effect of the residual errors of an on-line correction protocol 

and intra-fractional motion of the prostate on the PTV margins. 

Materials: Between Sept 2006-Jan 2008, 44 patients received radical radiotherapy 

to the prostate gland. Three intra-prostatic gold seeds were inserted 

under ultrasound guidance one week prior to CT planning. Immediately prior 

to each fraction, two orthogonal megavoltage images were obtained using 

treatment portals. The Acculoc TM prostate localisation software was used to 

match marker locations to those planned and calculate an automated on-line 

3D analysis. The patient was repositioned prior to treatment exposure, using 

a corrective movement threshold of ≥ 2mm each day. Two further positional 

analyses were calculated: following prostate realignment prior to radiotherapy 

and at the end of the fraction. PTV margins were calculated using the 

van Herk formula (including random errors from this study and the phantom 

transfer errors of this IGRT system). 

Results: 4,884 positional data were analysed. The residual errors (mm), Σ 

and (σ) after the on-line correction protocol was applied were 0.38 (1.07), 

left-right (L-R), 0.61 (1.42) superior-inferior (S-I) and 0.85 (1.67) anteriorposterior 

(A-P). These values changed to 0.60 (1.30), 1.32 (2.10) and 1.70 

(2.28) respectively by the end of the fraction. Assuming theoretical complete 

correction of Σset-up/organ motion a PTV margin of 3.2mm (L-R), 3.3mm (S- 

I) and 3.5 mm (A-P) would be required. Inclusion of residual errors present 

before the treatment exposure starts requires the respective margins to be 

increased to 3.3mm, 3.7mm and 4.1mm. Inclusion of intra-fractional motion 

requires margins of 3.6mm, 5.2mm and 6.0mm. 

Conclusions: This study has demonstrated that if residual errors and intrafractional 

motion are to be accounted for, a PTV margin increase of 58% in 

the S-I direction and 71% in the A-P direction is required. This highlights the 

importance that disregarding these errors will underestimate the PTV margin 

required and could risk local tumour control. 


1168 poster 

S 373 

INVESTIGATING THE EXPECTED CLINICAL IMPACT OF DAILY 

MEGAVOLTAGE CT REGISTRATION ON ADAPTIVE RADIOTHERAPY 

WITH HELICAL TOMOTHERAPY 

P. Mavroidis 1 , F. C. Su 2 , D. Giantsoudi 2 , S. Stathakis 2 , G. Komisopoulos 

3 , C. Shi 2 , G. Swanson 2 , C. Ha 2 , N. Papanikolaou 2 





3 UNIVERSITY HOSPITAL OF LARISSA, Department of Medical Physics, 

Larissa, Greece 

Purpose: For reducing setup uncertainties, MVCT image sets have to be acquired 

to account for daily changes in the patient internal anatomy and setup 

position. Furthermore, a comparison with the kVCT study used for dosimetric 

planning must be performed resulting in repositioning the patient according to 

specific transitional and rotational shifts. This study aims to investigate the expected 

clinical impact of patient setup correction using the HiArt tomotherapy 

system. 

Materials: In this study, a new module of the tomotherapy software (TomoTherapy, 

Inc, Madison, WI) is employed by which, eventual dose discrepancies 

in patient setup can be corrected before treatment. In this process 

the delivered dose can be calculated for each fraction. The calculation was 

done for almost all the treatment fractions, and was subsequently compared 

to the planning dose for the same number of fractions. Using this method, 

patients treated for lung, pancreas and prostate carcinomas are evaluated. 

In each cancer case, two dose distributions were calculated using the MVCT 

image sets with and without patient setup correction. The dose distributions 

are compared by using common dosimetric measures as well as the biologically 

effective uniform dose (BEUD) and the complication-free tumor control 

probability (P+). 

Results: For the lung cancer case, at the optimum dose levels of the two 

dose distributions, the, P+ values are 57.6% and 56.8%, respectively. The 


corresponding total complication probabilities, PI are 20.5% and 21.3%. For 

the pancreas cancer case, at the optimum dose levels of the two dose distributions, 

the P+ values are 95.0% and 97.5%, respectively. The PB values 

are 97.8% and 98.7%, whereas the PI values are 2.9% and 1.2%. For the 

prostate cancer treatment plan, at the optimum dose levels of the two dose 

distributions, the P+ values are 57.7% and 55.9%, respectively. The PB values 

are 83.7% and 84.7%, whereas the PI values are 26.1% and 28.8%. The 

expected outcome of the treatment changed by almost 3%. 

Conclusions: According to our results, in Helical Tomotherapy, which is characterized 

by highly conformal dose distributions, the necessary target localization 

can be achieved through translational and roll corrections. In clinical 

cases, which may look dosimetrically similar, traditional dose based evaluation 

tools can be complemented by the use of P+BEUD diagrams to compare 

treatment plans.


1169 poster 

IS ON-LINE POSITION CORRECTION SUFFICIENT FOR ADEQUATE 

TREATMENT OF BLADDER TUMOURS? 

D. van Rooijen 1 , J. van de Kamer 1 , M. Kamphuis 1 , H. Lotz 1 , M. Hulshof 

1 , A. Bel 1 

1 ACADEMIC MEDICAL CENTER, Radiation Oncology, Amsterdam, Nether- 

lands 

Purpose: The position of a bladder tumour can have a large day-to-day variation. 

Therefore bladder cancer patients will benefit from on-line position 

verification. Because variation in the tumour position can be up to several 

centimetres, the question raised whether it is reasonable to assume that applying 

position correction is equal to shifting the planned dose distribution. In 

this study we investigated the dosimetric effect of position corrections through 

repetitive full dose calculations for different internal organ shifts. 

Materials: For ten patients 5-beam IMRT plans were made with a CTV-PTV 

margin of 5 mm. The prescribed dose to the PTV is 60 Gy. For each patient 

data of tumour motion were available for 7-9 fractions. With the individual 

mean and SD of these data, tumour motions per patient were created for all 

fractions with a pseudo-random number generator. In APLAN, an in-house 

developed software tool for evaluating 4D dose distributions, the dose distribution 

for the boost was calculated as if on-line position correction had been 

applied. The position variation of the tumour is with respect to the body contour 

and position correction of the displaced tumour is assumed to be perfect. 

Target coverage using on-line position correction was compared with target 

coverage without on-line position correction. 

Results: For three out of ten patients, the CTV was not entirely covered by 

the 95% isodose if on-line position correction was not applied. For these 

patients the volume that was covered by the 95% isodose was 93.5%, 88.1% 

and 80.2%, respectively. For two of these three patients, the CTV was also 

not adequately covered if on-line position correction would have been applied. 

For these two patients the volume that was covered by the 95% isodose was 

96.5% and 82.1%, and the mean dose to the target decreased with 2.4% and 

5.9% respectively. This effect is caused by a changed position of the tumour 

with respect to the body contour. The altered depth of the tumour makes the 

beams pass through more tissue, resulting in a lower dose in the target. The 

opposite effect, a higher dose in the CTV, also occurred in one patient. 

Conclusions: Using on-line position correction is not enough to ensure adequate 

target coverage for bladder tumours. Solutions can be found in on-line 

re-planning, in making plan libraries or in finding an appropriate margin to 

overcome this problem. 

1170 poster 

METHOD COMPARISON ANALYSIS OF CONE-BEAM CT (CBCT) 

AND STEREOSCOPIC KV X-RAY (KVX) POSITIONAL VERIFICATION 

FOR HEAD AND NECK. 

C. D. Fuller 1 , T. Scarbrough 2 , M. Choi 3 , J. J. Sonke 4 , C. Rasch 4 , J. Ting 

2 , D. Rosenthal 5 

1 UTHSCSA, Department of Radiation Oncology Radiological Sciences/Radiology, 

San Antonio, USA 

2 MIMA, Radiation Oncology, Melbourne, USA 


4 NKI-AVL, Radiation Oncology, Amsterdam, Netherlands 

5 UT MD ANDERSON, Radiation Oncology, Houston, USA 

Purpose: Direct comparison between distinct IGRT platforms for head and 

neck positional verification is rarely performed; we sought to evaluate CBCT 

and kVX techniques using accepted method comparison analyses. 

Materials: A sequential series of 33 patients (pts) from MIMA Cancer Center 

with tumors of the head and neck. Pts were immobilized with thermoplastic 

facemasks and custom-formed headrests, without shoulder immobilization. 

Approximately biweekly, pts were set-up to mask markings via inroom 

lasers, and kVX images obtained, followed within 2 minutes by CBCT 

acquisition. Setup error (device-measured offset from initial in-room laser 

alignment to isocenter) was assessed by registration of AP and lateral digitally 

reconstructed radiographs (DRR) with stereoscopic AP and lateral kVX 

images, followed by allineation of CBCT with the simulation CT. kVX/DRR 

and CBCT/CT pairs were automatched using Varian OBI v1.3 software, with 

software derived directional shifts in the lateral (X), anteroposterior (Y), and 

craniocaudal (Z) axes. Between-method shift agreement was compared with 

Altman-Bland methodology. Orthogonal regression was performed to determine 

bias-corrected correlation. 

Results: 100 total daily positional assessments were performed. The average 

difference between daily measures in the X, Y, and Z dimension were 0.2, 

-0.4, and 1.1 mm, with corrected standard deviation of differences of ±5.7, 

±4.8, ±2.8 mm. Orthogonal regression demonstrated variance-weighted 

correlation coefficient of 0.54, 0.74, and 0.81 in the X-, Y-, and Z-axes. A 

proportional bias was detected at the p=0.05 level in the X- and Z-axes. 

Conclusions: CBCT and kVX positional verification measurements using the 

same automated matching software show distinct distributional parameters 

when performed on the same patient near simultaneously, with poor correlation 

and standard deviation of measurements between devices. Post-hoc 

phantom-based quality assurance demonstrated geometric agreement within 

1 mm for all directions. Clinicians must recognize that software suggested 

shifts may result in distinct set-up distributions when using differing imaging 

modalities, and correct IGRT protocols as required. 

1171 poster 

MRI-COMPATIBLE FIDUCIAL MARKERS FOR PROSTATE CANCER 

PATIENTS 

G. Bol 1 , U. van der Heide 1 , A. Kotte 1 , M. van Vulpen 1 , J. Lagendijk 1 

1 UNIVERSITY MEDICAL CENTER, Radiotherapy, Utrecht, Netherlands 

Purpose: Fiducial markers in the prostate are an effective tool for improving 

the positioning accuracy of patients during external-beam radiotherapy. The 

accuracy of delineation of the prostate can be improved using MR imaging. 

As solid gold markers are poorly visible on most MRI sequences, registration 

is required between the MRI and CT scans. This procedure may introduce 

a systematic error in the treatment. To benefit optimally from the combination 

of marker based position verification and MRI delineation, we developed 

fiducial gold markers with a steel core, that are visible on CT and epid as 

well as the MRI images. This allowed us to study the errors introduced in the 

conventional procedure and quantify the benefits of MRI-visible markers. 

Materials: The MRI-compatible marker (fig. A) consists of a gold cylinder 

of 5 x 1 mm with a 0.3 mm center core made of surgical steel. The steel 

core causes an artifact on the MRI while the gold casing ensures detectability 

on portal imaging devices. For 20 patients, implanted with 3 markers, an 

MRI exam was made on a Philips 3T scanner. The exam consisted of a 

T1, a T2 and a steady-state free precession (SSFP) scan. Also a regular 

planning CT scan was made. The SSFP scan was registered to the CT using 

mutual information. The markers were clearly visible on all scans and their 

position was identified by the center of mass of the artifacts (fig. B). For each 

marker the distance was determined between the positions identified on the 

four scans. 

Results: For the 60 markers the distance between the marker positions identified 

on CT and SSFP scan were 0.2 ± 0.5 mm in the lateral, -0.5 ± 1.8 mm 

in the AP and -0.3 ± 1.7 mm in the cranio-caudal direction. This indicates the 

registration error between the two scans. In the absence of MRI-compatible 

markers this error would not be detected, but would introduce a systematic 

error in the treatment. Comparing the T1 and T2 with the SSFP scans we find 

distances between the marker positions of 0.3 ± 0.7 mm in the lateral, 0.3 

± 1.6 mm in the AP and -1.2 ± 2.1 mm in the cranio-caudal direction. This 

reflects intra-scan motion of the prostate as well as partial volume effects in 

the slice direction. 

Conclusions: Fiducial gold markers with a surgical steel core are visible on 

MRI. As a result, the same MRI sequence can be used for both delineation of 

the prostate and identification of the marker position. This approach reduces 

the systematic error in the treatment. 

1172 poster 

NON-RIGID ORGAN MOTION IN CERVICAL CANCER PATIENTS: 

ARE THE CERVIX AND UTERUS SHAPE AND POSITION PRE-

DICTABLE? 

M. Bondar 1 , M. Hoogeman 1 , G. Dhawtal 1 , J. W. Mens 1 , E. Vasquez 

Osorio 1 , I. de Pree 1 , S. Quint 1 , R. Ahmad 1 , B. Heijmen 1 



Purpose: Large non-rigid motion of the cervix and uterus requires generous 

CTV-to-PTV margins in the EBRT treatment of cervical cancer. Bladder filling 

has a large impact on the position and shape of the cervix-uterus, but the 

extent of motion and the bladder vs. cervix-uterus relationship are patient 

dependent. The aim of this study was to develop and evaluate a patient specific 

prediction model for the shape and position of the cervix-uterus based 

on measured bladder volumes. The model could be used to generate patient 

specific margins and to assist in online adaptation of the treatment plan. 

Materials: For four cervical cancer patients a planning CT scan with a full 

bladder and four subsequent repeat CT scans with a naturally filling bladder 

(empty to full) were acquired in prone position. The cervix-uterus, bladder, 

and rectum were manually contoured in the in total 20 CT scans. After a rigid 

CT bone match the repeat cervix-uterus surfaces were non-rigidly registered 

to the planning by using a registration method [1] modified to enforce point 

correspondence consistency. The patient specific model was developed by 

fitting the coordinates of the registered points of the surfaces to linear functions 

of the bladder volume. The predictability of the model was estimated by 

using leave-one-out cross-validation. The error of the model is reported as 

1) the RMS errors in LR/AP/IS directions and 2) the surface distance error 

(SDE) between the predicted and observed shapes. 

Results: The registration error was small, with an average mean transformation 

error of 0.2±0.2 mm (1 SD) and a mean correspondence error 

of 0.9±0.8 mm (1 SD). The impact of bladder filling on the position and 

shape of the cervix-uterus was patient specific; within the patient group the 

maximum observed displacement of the cervix-uterus ranged from 8 to 46 

mm for a bladder volume range of 57 to 730 ml. The RMS errors of the 

prediction model and the SDE error averaged for the patient group were 

4.1±2.5/5.2±1.8/4.8±2.0 mm in LR/AP/IS direction and 3.6±2.6 mm, respectively. 

Delineation inaccuracies and large displacements resulted in a 

lower predictability of the model. 

Conclusions: Large inter-patient variability requires the development of patient 

specific models to predict the location and shape of the cervix-uterus as 

a function of bladder volume. The level of accuracy of the prediction model 

makes it useful to facilitate the online adaptation of treatment plans. Further 

refinements of the model and analysis of data of more patients are currently 

in progress. References [1] Vues Osorio et al, Int J Radiat Oncol Biol Phys. 

2008 Mar 1;70(3):875-8 

1173 poster 

PHANTOM STUDY ON THE EFFECT OF STRUCTURE CONTRAST 

AND PARAMETER SETTINGS ON THE ACCURACY OF A B-SPLINE 

BASED METHOD FOR IMAGE REGISTRATION IN THE HEAD AND 

NECK AREA 

H. Meertens 1 , C. Brouwer 1 , L. Hogeweg 1 , H. Langendijk 1 , P. van Luijk 1 , 

A. van ’t Veld 1 



Purpose: Significant changes in the position of the salivary glands during the 

course of radiotherapy have been observed in clinical H&N studies. These 

changes might compromise the dose to relevant structures. Possibly this effect 

can be reduced by making new treatment plans during the course of 

treatment and adapt in this way the dose delivery to the observed changes. 

This adaptive process requires image registration, such as a B-Spline based 

Registration Method (BSRM), as a tool to register non-rigidly deformed CTdatasets 

and to quantify rigid displacements and deformations. Purpose 

study: testing of the BSRM as a method for deformable intensity based image 

registration for low contrast structures in a H&N phantom and evaluation of 

the effect of contrast and signal to noise ratio on the accuracy of the measured 

voxel displacements. 

Materials: CT images of a cubic 10x15x25 cm phantom with voxel size of 

1x1x2 mm, an average CT value of 0 HU and a noise of 10 HU (1SD) were 

constructed. The phantom contained circular and elliptical structures simulating 

the two parotid glands, a tumor and the spinal cord. From this set, 

alternative sets were constructed by application of : 1) an affine transform, 2) 

different known deformations and 3) alternative sets in which the CT values of 

the parotid and tumor structures were varied from 500 down to 10 HU simulating 

a decrease in contrast. The BSRM provided by the Insight Toolkit 1 was 

used to register the various transformed CT phantom data to the original CT 

phantom data. Displacement vectors are computed using B-spline interpolation 

from the displacement values of points located in a coarse B-spline grid 

(5 to 15 mm). The effect of different parameter settings of the registration, 

like the number of iterations, the spacing of the B-spline grid, the number of 

resolution levels, has been investigated. Computed deformation vectors were 

compared with the set of deformation vectors used to generate the deformed 

phantom images. In addition for each set of corresponding slices the sum of 

the squared differences per pixel and the normalized correlation coefficient 


S 375 

were used to evaluate the results. 

Results: Preliminary results show that the local contrast and signal to noise 

ratio of a structure in the H&N phantom determine to a great extent the accuracy 

of the measured displacement of voxels of that structure. This is especially 

the case for a structure with a low contrast (40-80 HU) to its surrounding, 

like the contrast of parotid and the submandibular glands in a patient. In addition 

all parameter settings affect the accuracy of the displacement vectors 

and the time needed for registration. A tracking accuracy of better than 2 mm 

for parotid gland edges seems feasible 

Conclusions: The BSRM seems to be suitable for intensity based deformable 

image registration of structures like the parotid and submandibular 

glands in the H&N region. Careful tuning of different parameter values is 

important to obtain reliable results. References: 1. ITK http://www.itk.org 

1174 poster 

PLANNED VS. DELIVERED DOSE DISTRIBUTIONS WITH AND 

WITHOUT PATIENT SETUP CORRECTION IN HELICAL TOMOTHER- 

APY 

N. Papanikolaou 1 , S. Stathakis 1 , P. Mavroidis 2 , C. Ha 1 





Purpose: To quantify the differences between highly conformal planned dose 

distributions and their delivered dose distributions with and without patient 

setup correction, using radiobiological measures. To investigate the expected 

clinical impact of these differences, Helical Tomotherapy (HT) was employed 

using the Helical Megavoltage CT (MVCT) scanner of the tomotherapy unit. 

Materials: A head and neck cancer case was used to study the accuracy 

of dose delivery. Right parotid, left parotid and spinal cord are the organs 

at risk proximal to the internal target volume (ITV). MVCT images were acquired 

daily on a helical tomotherapy unit (TomoTherapy, Inc., Madison, WI) 

before and after the patient setup correction. While these images are used 

primarily for patient alignment, they were also used to recalculate the treatment 

plan for the patient anatomy of the day. The biologically effective uniform 

dose (BEUD) together with the complication-free tumor control probability 

(P+) were used to compare the planned and delivered (with and without 

patient setup correction) dose distributions by plotting the tissue response 

probabilities vs. BEUD. 

Results: For the treatment plan, the maximum value of P+ was 88.3%, for 

a BEUDITV of 85.0 Gy. The total control probability, PB was 97.3% and the 

total risk for complications, PI was 9.3%. For the delivered dose distribution 

with patient setup correction in every fraction using the MVCT method the 

value of P+ was 87.2% for a BEUDITV of 83.6 Gy. The response probabilities 

PB and PI were 92.7% and 5.5%, respectively. Finally, for the delivered dose 

distribution without patient setup correction in every fraction, the value of P+ 

was 79.8% for a BEUDITV of 77.2 Gy. The response probabilities PB and PI 

were 83.6% and 3.8%, respectively. These results indicate that the expected 

effectiveness of the treatment plan dropped by a ∆P+ of 1.1% and 8.5% if 

the patient had been treated with and without setup correction, respectively. 

Conclusions: In the highly conformal dose distributions of HT, the reliability 

of the patient setup procedure is critical for the effectiveness of the treatment. 

For effective evaluation and comparison of such dose distributions, dosimetric 

evaluation tools should be complemented by P+ BEUD diagrams. The figure 

illustrates how the effectiveness of the dose distribution drops between the 

treatment plan and the dose delivery with and without patient setup correction 

in terms of DVHs and dose-response curves.


1175 poster 

POSITIONING ACCURACY IMPROVEMENT USING CONE BEAM CT 

FOR RECTAL CANCER PATIENTS 

M. Sastre Padró 1 , M. Engstrøm 1 , J. Rødal 1 , E. Malinen 1 , K. Eilertsen 1 

1 RIKSHOSPITALET, Medical Physics, Oslo, Norway 

Purpose: To assess the treatment positioning accuracy of rectal cancer patients 

using kilovoltage cone-beam computed tomography (CBCT). 

Materials: For 18 patients with rectal cancer receiving fractionated radiotherapy 

at an Elekta Synergy unit, CBCT images were acquired prior to treatment. 

The setup error at a given treatment session was measured by automatically 

matching the CBCT images with planning CT images using bone structures 

found in both image sets. The patients were repositioned according to the 

estimated setup errors. By portal imaging during treatment and subsequent 

manual matching with digitally reconstructed radiographs from planning CT 

images, the residual setup error was estimated. 

Results: A total of 118 CBCT images sets were analyzed. Quite large setup 

errors were observed for these patients. The population based systematic 

setup error was 2.9, 1.3 and 2.1 mm in the medial-lateral, caudio-cranial and 

dorsal-ventral direction, respectively. The population based random setup error 

was 2.8, 2.4 and 4.5 mm, respectively. After patient repositioning, the 

systematic error was 0.9, 0.7 and 1.0 mm, respectively. The corresponding 

random error was 1.4, 1.4 and 1.3 mm, respectively. Thus, both the systematic 

and random setup error were reduced by about 60 % following repositioning 

using CBCT. 

Conclusions: The current work shows that CBCT imaging greatly improves 

the positioning accuracy for rectal cancer patients. 

1176 poster 

QUANTIFICATION OF VOLUMETRIC AND GEOMETRIC ANATOMIC 

CHANGES FOR HEAD-NECK (HN) CANCER PATIENTS TREATED 

WITH HELICAL TOMOTHERAPY (HT) 

E. Maggiulli 1 , S. Broggi 1 , C. Fiorino 1 , I. Dell’Oca 2 , G. M. Cattaneo 1 , F. 

Ferruccio 3 , R. Calandrino 1 

1 H.S.RAFFAELE, Departement of Medical Physics, Milano, Italy 

2 H.S.RAFFAELE, Department of Radiotherapy, Milano, Italy 

3 H.S.RAFFAELE AND IBFM, Department of Radiotherapy and CNR, Milano, 

Italy 

Purpose: To quantify volumetric and geometric changes in body contour, 

parotid glands and air cavities as assessed by daily Megavoltage CT (MVCT) 

during tomotherapy of HN cancer. 

Materials: Twelve HN cancer patients (4 nasopharynx (N), 5 oropharynx (O), 

3 post-operative (PO)) irradiated with a simultaneous integrated boost approach 

(30 fractions) were considered. Daily MVCT scans were acquired to 

assess and correct patient set-up error. Body contour’s variation was estimated 

considering 12 MVCT scans (2 scans for week) for each patients, by 

measuring the body thickness in some defined anatomic position: skull base, 

C2, C3-C4, C4-C5 vertebral body. Parotid glands and air cavities were manually 

contoured on three MVCT scans (start-middle-end treatment) for radical 

N and O patients. Volumetric changes and positional shifts in medial, cranialcaudal, 

anterior-posterior directions were measured for these structures. 

Results: Body contour thickness shows a linear decrease with time; average 

thickness reductions between the start and the end of the therapy were 0.6 

cm (1SD=0.25), 1.2 cm (1SD=0.31) and 0.7 cm (1SD=0.26), for N, O and 

PO patients respectively. Parotid gland volume significantly decreases during 

irradiation: a global mean volume reduction equal to 25% (0.2 - 59.3%) and 

22% (0 - 49.2%), was found for N and O patients respectively. When comparing 

parotid volume reduction in the first and in the second half of the treatment 

(Figure 1), most of volume reduction was in the first part ( 20.6 % in the first 

half vs 1.3 % in the second half, p

Materials: Patients with locally advanced, inoperable non small cell lung cancer 

are enrolled in a clinical protocol for curative treatment with 66 Gy in 33 

fractions. For treatment planning a 4D-FDG-PET/4D-CT with phase correlated 

attenuation correction of the PET in treatment position was performed 

(Biograph 16, Siemens). Each series is devided into 8 phases and thus yields 

8 Gross Tumour Volumes (GTV), that are merged to the Internal Target Volume 

(ITV). The ITV-PET and ITV-CT are merged to the ITV0. The Clinical 

Target Volume (CTV) is generated from the ITV0 + 7 mm, and the Planning 

Target Volume (PTV) for the first 6 fractions from the CTV + 8 mm. The 

PTV margin is reduced to 5 mm after 6 fractions if the ITVN=1-5 (N: number 

of fraction) are positioned within the CTV. For treatments patients are 

positioned by X-ray verification (ExacTrac-Xray, BrainLab). Repeated 4D-CT 

scans are acquired with an in-room CT (Primatom, Siemens) immediately before 

treatment for the first 5 fractions and subsequently twice per week (i.e. 16 

repeated 4D-CTs per patient). Immediate evaluation of the 4D-CT includes 

the verification of patient positioning and adequateness of treatment fields 

(Pinnacle, Philips). Further evaluation of data analyses the breathing-phase 

dependent as well as the interfractional variability of tumour volume. Margins 

will be evaluated simulating gated radiotherapy. 

Results: The protocol started in January 2008. Up to now 5 patients are 

enrolled, 2 of them have completed their treatment. For the first 5 patients a 

PTV reduction to 79.5 % (SD = 2.1 %) after the first treatment week could be 

reached, which led to a decrease of Mean Lung Dose of 0.7 Gy (SD = 0.3 

Gy). Preliminary evaluation of the 4D data shows a minor phase dependent 

variability of the tumour volume compared to greater interfractional variations. 

To a first assessment this appears to be a variability in manual contouring the 

GTV for each CT scan than a true variability in tumour volume. 

Conclusions: The preliminary data suggest only small setup variability during 

treatment. Extension of the data base and further analysis will address if 

dose escalation by introducing gated radiotherapy is possible. Supported by 

BMBF (03ZIK/OncoRay) and Siemens Medical Solutions. 

1179 poster 

SBRT TREATMENTS: REDUCTION OF DIAPHRAGMATIC AND 

TUMOUR EXCURSION BY MEANS OF FORCED SHALLOW 

BREATHING WITH ABDOMINAL COMPRESSION. ASSESSMENT 

BASED ON 2504 TREATED TUMOURS. 

K. Karlsson 1 , G. Gagliardi 1 , E. Rutkowska 2 , I. Lax 1 

1 


Sweden 

2 

UNIVERSITY OF LIVERPOOL, Liverpool, United Kingdom 

Purpose: Several strategies are available to keep under control respiratory 

motions in radiotherapy. At Karolinska University Hospital abdominal compression 

has been routinely used in SBRT treatments to keep the craniocaudal 

(CC) diaphragm excursion within 10mm. Purpose of the study is to 

assess the efficacy of this method. 

Materials: This retrospective analysis is based on 1689 patients treated with 

SBRT in the Stereotactic Bodyframe between 1994 and 2006. Data were retrieved 

from a form routinely filled in at simulator with information on diaphragmatic 

and lately also tumour movements measured by fluoroscopy. The total 

numbers of tumours was 2504 of which 1248 located in lungs, 200 in the mediastinum, 

579 in the liver, 464 in the abdomen, 6 outside the trunk. For 7 

tumours information on location was not available. A total of 1182 tumours 

was treated in free breathing, 1322 with abdominal compression. Information 

on both tumour and diaphragmatic movements in the CC direction were 

given for 81 lung tumours, 62 treated in free breathing and 19 with abdominal 

compression. 

Results: The mean diaphragmatic CC excursions for tumours treated with 

abdominal pressure was 10.3mm (1st, 2nd, 3rd quartile:9,10,11). For these 

cases the mean diaphragm excursion before applying the pressure was 

18.1mm. For tumours treated in free breathing it was 11.4mm (1st, 2nd, 3rd 

quartile:10,10,12). In free breathing treatments the mean tumour CC excursion 

was 4.9mm; for those treated with the pressure it was 8.0mm (13.0mm 

before applying the pressure). Abdominal pressure was used mostly for lung 

tumours. Tumour and diaphragmatic CC movements were both available for 

81 lung tumours. Out of 30 tumours located above hilus, 27 were treated 

in free breathing with a mean tumour CC excursion of 3.7mm and a corresponding 

value for diaphragm of 14.2mm. Out of 51 tumours below hilus 35 

were treated in free breathing with a mean tumour, respectively diaphragm 

CC excursion of 5.6mm and 15.3mm. The remaining 16 tumours below hilus 

were treated with the pressure: the mean tumour respectively diaphragmatic 

longitudinal excursion was 8.4mm (without pressure: 13.8mm) and 10.2mm 

(without pressure: 15.3mm). 

Conclusions: These results show that the abdominal pressure method allows 

to keep the diaphragmatic CC excursion within 10 mm in most cases. 

Data on both tumour and diaphragmatic CC excursions indicate that tumour 

CC movements are smaller than the diaphragmatic ones. 


1180 poster 

S 377 

SIGNIFICANTLY REDUCING REGISTRATION TIME IN IGRT USING 

GRAPHICS PROCESSING UNITS 

K. Noe 1 , B. Denis de Senneville 2 , K. Tanderup 3 , T. Sørensen 4 

1 

UNIVERSITY OF AARHUS, Department of Computer Science, Aarhus N, 

Denmark 

2 

UNIVERSITÉ BORDEAUX, IMF, UMR 5231 CNRS, Bordeaux, France 

3 

AARHUS UNIVERSITY HOSPITAL, Aarhus C, Denmark 

4 

UNIVERSITY OF AARHUS, Department of Computer Science and Institute 

of Clinical Medicine, Aarhus N, Denmark 

Purpose: For online IGRT, rapid image processing is needed. Fast parallel 

computations using graphics processing units (GPUs) have recently been 

made more accessible through general purpose programming interfaces. We 

present a GPU implementation of the Horn and Schunck method for deformable 

registration of 4DCT lung acquisitions to exemplify the use of GPUs 

in IGRT. 

Materials: The registration is evaluated on the POPI-model acquired at the L 

Brd Cancer Center, France. It consists of thorax CT image series (resolution 

4826041 and voxel size 0.98.98.0 mm3) from 10 respiration phases in a free 

breathing volunteer and 41 anatomical landmark points in each image series. 

The registration method used is a multi-resolution GPU implementation of the 

3D Horn and Schunck algorithm. It is based on the CUDA framework from 

Nvidia. 

Results: On an Intel Core 2 CPU at 2.4GHz each registration took 30 minutes. 

On an Nvidia Geforce 8800GTX GPU in the same machine this registration 

took 37 seconds, making the GPU version 48.7 times faster. The 

nine image series of different respiration phases were registered to the same 

reference image (full inhale). Accuracy was evaluated on landmark distances 

before and after deformable registration. Original average landmark distance 

was 3.5 mm ± 2.0 mm (max = 14.0 mm). After registration, this average 

distance was equal to 1.1 mm ± 0.6 mm (max = 3.6 mm) which is well below 

the slice thickness of 2 mm. 

Conclusions: Using the GPU has led to a very significant reduction of the 

registration time due to the parallelized architecture of the GPU. Considering 

the slice spacing we find the registration result acceptable. The accuracy is 

comparable to previous results for the Demons algorithm in the POPI model 

(Vandemeulenboucke et al, ICCR 2007). The processing power of GPUs can 

be used for many image processing tasks in IGRT making it a useful and 

cost-effecient tool to help us towards online IGRT. 

1181 poster 

STABILITY OF LIPIODL AS MARKER FOR IMAGE GUIDED RADIO- 

THERAPY OF BLADDER CANCER 

X. Chai 1 , M. van Herk 2 , J. van de Kamer 1 , A. Bel 1 , P. Remeijer 2 , M. 

Hulshof 1 , F. Pos 3 

1 

ACADEMIC MEDICAL CENTER, UNIVERSITY OF AMSTERDAM, Radiology, 


2 

THE NETHERLANDS CANCER INSTITUTE-ANTONI VAN LEEUWENHOEK 


3 

THE NETHERLANDS CANCER INSTITUTE-ANTONI VAN LEEUWENHOEK 

HOSPITAL, Radiology, Amsterdam, Netherlands 

Purpose: The fatty radio-opaque substance lipiodol can be inserted with relative 

ease during cystoscopy to mark bladder tumor borders for target volume 

delineation and image guidance. However the instability of the marker shape 

is a potential disadvantage of lipiodol. The aim of this study is to quantify 

shape changes of the lipiodol markers and tumor and bladder shape change 

indicated by lipiodol markers. 

Materials: In 8 patients with bladder cancer, lipiodol was injected under cystoscopy, 

then a planning CT scan was made, followed by 6-9 cone beam CT 

(CBCT) scans during RT fractions distributed over the treatment period. All 

CBCT scans were first globally registered to corresponding planning CT using 

a chamfer matching algorithm on all segmented lipiodol markers together. 

For this purpose a region of interest was generated around the GTV, which 

was manually edited to exclude bone and include all lipiodol spots (which are 

as dense as bone). Using this global registration as starting point, each segmented 

lipiodol spot was next registered individually to quantify tumor/bladder 

deformation as local translation. Both registrations are restricted only translation. 

The residual cost function (the mean distance between the segmented 

features) was used to quantify deformation of the spots. For both quantities, 

M (overall mean), systematic error Σ (standard deviation of mean) and random 

error σ (RMS of standard deviation) were calculated. 

Results: The lipiodol spot deformation (distance and not direction specific) 

was small: M=0.05 cm, Σ=0.03 cm and σ=0.04 cm. No correlation between 

lipiodol deformation and treatment day was found, indicating very 

limited marker washout. In contrast, tumor/bladder deformations indicated 

by the spots were bigger: M=0.05cm, Σ=0.13cm and σ=0.21cm in L-R, 

M=0.01cm, Σ=0.13cm and σ=0.22cm in Cr-Ca and M=0.07cm, Σ=0.19cm 

and σ=0.22cm in A-P direction, respectively. One early patient had large 

tumor deformation, because the improper injection causes unconsistency of 

tumor deformation and lipiodol spot displacement.


Conclusions: Lipiodol marker shape change is negligible, and bladder/tumor 

deformation is small compared with tumor motion (SD 0.1-0.9 cm in C-C and 

A-P direction). Lipiodol injection is therefore an accurate and reliable method 

to indicate the position of bladder tumors. However, since improper injection 

may lead to large lipiodol displacement, one should be aware of potential 

marker deformation during treatment. 

1182 poster 

THE NORMAL TISSUE SPARING POTENTIAL OF ADAPTIVE 

STRATEGIES IN RADIOTHERAPY OF BLADDER CANCER BASED 

ON FIDUCIALS 

P. Wright 1 , A. Redpath 2 , J. Søndergaard 3 , M. Høyer 3 , C. Grau 3 , L. P. 

Muren 1 

1 

DEPT OF MEDICAL PHYSICS, Aarhus University Hospital, Aarhus C, 

Denmark 

2 

DEPT OF ONCOLOGY PHYSICS, Western General Hospital, Edinburgh, 


3 

DEPT OF ONCOLOGY, Aarhus University Hospital, Aarhus, Denmark 

Purpose: To improve the outcome in bladder RT we have investigated various 

adaptive treatment strategies involving on-board tumour/target visualisation 

using fiducials. The strategies are compared in terms of the amount of normal 

tissue enclosed within the PTV. 

Materials: CT data of five male bladder cancer patients having a planning 

and 7-8 repeat scans during treatment were used for this study. Various 

tumour positions (at the sup/inf/ant/post/left/right wall) were identified in the 

repeat scans based on a reference co-ordinate system. The origin of this 

system was positioned half-way between the centre of mass of the bladder 

and the entrance point into the bladder along an axis through the centres of 

masses of the prostate and the bladder. The repeat CTVs were translated, 

so that the tumour positions overlapped with the corresponding position on 

the planning CTV, whereafter the required margins were determined using a 

previously published margin calculation algorithm (Redpath and Muren, Radiother 

Oncol 2005; 77: 194-201). These calculations were performed both to 

find the margins required to enclose all repeat scans at the same time (standard 

PTV) and those to enclose the repeat scans one by one, i.e. simulating 

adaption on daily basis (adaptive PTV). Results were compared both with the 

case of optimising the margins for all repeat scans first without any shift of 

the contour (no image-guidance) and second after finding the best shift for 

the whole bladder in order to minimise the PTV volume (whole-bladder shift). 

Results: The volume of normal tissue enclosed within the PTV for the inferior 

and superior position’s standard PTVs was not notably different from the case 

of no image-guidance (Table 1). The standard PTV for the superior position 

gave the largest normal tissue volume. When covering all repeat scans the 

strategy of optimal shift is superior. Anyway, the single PTV strategy is most 

favourable in terms of normal tissue sparing. Compared to the standard PTV, 

the adaptive PTV nearly halved the volume of normal tissue included. 

Conclusions: By daily adaptation of the treatment the normal tissue irradiation 

could be considerably reduced. Further, this could open for dose escalating 

the tumour without increasing the side effects. 

1183 poster 

THE USE OF A DIETARY PROTOCOL - IS THERE ANY BENEFIT 

IN PROSTATE RADIOTHERAPY WITH OR WITHOUT IMAGE- 

GUIDANCE? 

Y. Rimmer 1 , R. Benson 1 , A. Lynch 2 , J. Treeby 1 , D. Routsis 1 , J. Fairfoul 

1 , A. Hoole 1 , A. Doble 3 , N. Burnet 4 

1 

ADDENBROOKE’S HOSPITAL, Oncology, Cambridge, United Kingdom 

2 

CAMBRIDGE RESEARCH INSTITUTE, Statistics, Cambridge, United 

Kingdom 

3 

ADDENBROOKE’S HOSPITAL, Urology, Cambridge, United Kingdom 

4 

UNIVERSITY OF CAMBRIDGE, Oncology, Cambridge, United Kingdom 

Purpose: Rectal distension on a patient’s planning CT scan is associated 

with an increased risk of biochemical and local failure after irradiation for 

prostate cancer if image-guided radiotherapy (IGRT) is not employed1. Daily 

prostate localisation using IGRT aims to reduce these inter-fractional rectal 

influences on organ motion but will have no effect on intra-fractional displacement. 

The use of diet modifications and laxatives to alter rectal filling varies 

widely, with little evidence of efficacy. This study evaluated whether a di- 

etary protocol could influence rectal distension at planning and the subsequent 

inter- and intra-fractional prostate motion during radiotherapy. 

Materials: 44 patients (pts) received IGRT (74Gy/37#) using intra-prostatic 

gold seed megavoltage verification. Portal images were taken daily, before 

a corrective action was applied and after radiotherapy. This data allowed 

inter- and intra-fractional analysis of translational and rotational prostate motion 

(Isoloc TM , MedTec R○). 20 pts (diet group-D) followed a low fibre diet 

advice plan and started oral laxatives prior to their CT planning scan until 

completion of radiotherapy. 24 pts (non-diet group-ND) received no instructions 

on rectal preparation. Rectal distension was assessed by calculation of 

the cross sectional area (CSA= rectal volume/length). 

Results: The median CSA (cm2) on the planning CT scan in D is 6.9 (5.8- 

8.1) compared to ND 10.1 (7.7-13.3), p=0.0074. A CSA > 11.2 cm2 (cut 

off value1) occurred in 10% of D and 42% of ND. The required corrective 

shifts in the anterior-posterior (A-P) direction if CSA 11.2 cm2 

were 0.2mm (SD 3.9) vs 5.6mm (SD 3.2), but were not statistically significant. 

No differences were found between D & ND for intra-fractional motion in 

any translational direction. However, differences were seen in pitch rotation 

(mean, -0.5 ◦ in D and 3.3 ◦ in ND), p

PHYSICS AND TECHNOLOGY : APPLIED DOSIMETRY E.G. EPID, GEL, QUALITY ASSURANCE 

Materials: The in-vivo dosimetry method was used to reconstruct the isocenter 

dose, Diso, in patient on the basis of correlation functions obtained by the 

ratios between the transit signals, St, and the mid-plane doses, Dm, measured 

in solid water phantoms. The method was implemented in six centers 

with a tolerance level of 5%. In particular in two centers we developed the invivo 

dosimetry for lung tumors. In the first center, the Elekta ABC device was 

used to irradiate five patients at the end of the inhale phase. In the second 

center, the long-term changes of the tumor configuration, were checked with 

the in-vivo dosimetry method for three patients. In both the centers, the electronic 

portal images (EPI) for every therapy fraction were analyzed to check 

the patient’s position and to reconstruct the D iso values. 

Results: In the center that used the ABC, correlations between the daily tumor 

shifts (by EPI) and the breath-hold volume (BHV) were observed. The 

intra-fraction and the inter-fraction reproducibility of lung tumor position presented 

variations up to 4 mm (1 SD). Moreover, the in-vivo dosimetry confirmed 

the need to irradiate the patient with a reproducible BHV. For the three 

patients, treated in the second center, the ratios, R, between reconstructed 

doses Diso and planned doses, Diso,TPS, were observed systematically out 

of the tolerance level after 15-20 Gy. For all the cases it was decided not to 

change the treatment to ensure the sterilization of the sub clinical disease. 

However new CT scans were acquired and the R values, obtained by the 

hybrid plans, were well within the tolerance level. 

Conclusions: The tumor position reproducibility can change with the BHV. 

For this reason the treatments with the ABC device were supported by: (i) the 

EPI analysis in every treatment fraction and (ii) the D iso value reconstruction. 

On the basis of results obtained in the second center, it has been planned to 

repeat the CT scan when the ratio R is systematically out of tolerance level of 

5%. 

1186 poster 

USE OF IGRT IN SBRT TREATMENTS, UTSW EXPERIENCE 

E. Papiez 1 , R. Timmerman 1 

1 UTSOUTHWESTERN MEDICAL CENTER, Radiation Oncology, Dallas, USA 

Purpose: To present an impact of CBCT on efficiency and accuracy of SBRT 

treatments in case of lung and prostate tumors. 

Materials: Patients interfraction and intrafaction setup errors have been analyzed 

for prostate SBRT treatments and for lung SBRT treatments. The CBCT 

has been utilized for this purpose. Three and more fiducial markers have 

been implanted in prostate and their absolute position in laboratory frame 

of reference has been determined by volumetric reconstruction of CT cone 

beam images for patients after their setup for treatment. The localization software 

has been used then for determination of translations in three dimensions 

before each treatment (deformations and rotations have been ignored in comparisons 

between original, planned positions of markers and reconstructed in 

CBCT positions of markers). Similar measurements have been performed to 

determine translations between planned and CBCT reconstructed positions 

of tumor centers (without markers used) for lung cancers. The CBCT measurements 

of shifts before the end of treatment have been also collected for 

comparisons. 

Results: 

1. : Average interfractional shift for SBRT prostate treatments in vertical 

direction was -0.51cm with average deviation from mean of 0.29cm 

and with maximal shift of 1.3cm, in longitudinal direction these values 

were respectively -.01, 0.29 and 0.6cm and in lateral direction these 

values were 0.05, 0.22 and 0.8cm respectively. 

2. Average intrafractional shift for SBRT prostate treatments in vertical 

direction was -0.05cm with average deviation from mean of 0.07cm 

and with maximal shift of 0.2cm, in longitudinal direction these values 

were respectively 0.07, 0.12 and 0.5cm and in lateral direction these 

values were -0.08, 0.1 and 0.2cm respectively. 

3. Average interfractional shift for SBRT Lung treatments in vertical direction 

was -0.24cm with average deviation from mean of 0.37cm and 

with maximal shift of 1.1cm, in longitudinal direction these values were 

respectively -.06, 0.41and 0.8cm and in lateral direction these values 

were -0.11, 0.34 and 0.9cm respectively. 

4. Average intrafractional shift for SBRT Lung treatments in vertical direction 

was -0.01cm with average deviation from mean of 0.06cm and 

with maximal shift of 0.2cm, in longitudinal direction these values were 

respectively 0.01, 0.04 and 0.3cm and in lateral direction these values 

were 0, 0.05 and 0.3cm respectively 

Conclusions: Daily use of CBCT IGRT for patient setups indicates that daily 

corrections of setup errors at treatment justify reduction of margins in SBRT 

treatments of lung and prostate. 

S 379 

Physics and technology : Applied 

dosimetry e.g. EPID, Gel, quality 

assurance 

1187 poster 

HIGH DOSE RATE BRACHYTHERAPY: IN VIVO DOSIMETRY OF 

RADIATION DOSE TO THE RECTUM 

A. Ullén 1 , P. Gorzov 1 , J. Nilsson 2 , C. Holmberg 1 , M. Lundell 2 , K. M. 

Kälkner 1 



Purpose: During high dose rate (HDR) brachytherapy extremely high doses 

are delivered into the tissue immediately adjacent to the sources, but a rapid 

decline in dose over short distance makes it possible to create a favorable 

dose-distribution. In order to verify the dose delivery to the rectum during 

HDR brachytherapy with Ir -192 sources, thermolumeniscens dosimetry 

(TLD) was used for measurement in vivo 

Materials: The dose to the rectum was measured during 60 HDR treatments 

in 30 patients with localized prostate cancer treated with neoadjuvant hormonal 

therapy, external radiotherapy (2 Gy per fraction, 25 fractions) combined 

with a boost of HDR brachytherapy (10 Gy per fraction, 2 fractions). 

The patients were selected by large prostate volume (>50cc) and/or cases 

of high rectal dose found at the pre-planned dose-plan. Our dose constraint 

limits set by our department is 7 Gy to a rectal mucosa volume.A series of 12 

TLDs, each 6 mm in length, were placed into a thin (.6 mm) catheter. This 

catheter was fixated on the rectal ultrasoundprobe and in position during the 

entire treatment. Before irradiation started, the ultrasoundprobe was adjusted 

2 cm further in the rectum. The measured dose was then compared to the 

dose calculated according to the pre-planned dose-plan.TLD. principal figure 

demonstrating a thin catheter covering 12 TLDs on a ultrasoundprobe. 

Results: 56 of 60 measurements were successful. During two treatments the 

catheter including the TLD was not fixated. This happened in the beginning of 

this series of measurements. In two cases several of the TLDs were unreadable. 

In 7 cases (12%) the measured TLD dose exceeded the dose constraint 

limits set by our department. The average length of rectum receiving higher 

dose was in these cases 24 mm. 

Conclusions: TLD measurements can be used as a method of quality assurance 

and make it possible in future to analyse the correlation between 

delivered dose and occurrence of side effects. However, the need persists for 

developing an on-line measurement system.

S 380 PHYSICS AND TECHNOLOGY : APPLIED DOSIMETRY E.G. EPID, GEL, QUALITY ASSURANCE 

1188 poster 

A FAST AND RELIABLE METHOD TO CALIBRATE RADIOCHROMIC 

FILMS FOR DOSIMETRIC CALIBRATION AND VERIFICATION IN 

IORT (INTRAOPERTIVE RADIOTHERAPY) 

L. Fontan 1 , D. Canonico 1 , L. Bindoni 1 , L. Mantovani 1 , V. Tonetto 1 , M. 

Princivalli 1 

1 FISICA SANITARIA, ULSS 9, Treviso, Italy 

Purpose: Beams with high dose per pulse make radiochromic films a diffusely 

adopted tool for quality assurance. As known, every film stock needs 

to be accurately calibrated of different beam quality and for a wide dose range. 

The standard method consist in irradiating at various doses a number of films, 

laying in a plane orthogonal to the beam axis at the reference depth in a water 

phantom, in order to draw the calibration curve. This method is time consuming 

and care must be taken especially to accurately position the film in water. 

The method described in this work is aimed to make a fast and reliable film 

calibration useful for dose verification and calibration of intraoperative radiotherapy 

electron beams. 

Materials: Radiochromic film: Gafchromic R○HS type films from ISP Technologies 

Inc.; linac: Siemens Oncor Impression Plus calibrated in accordance 

with IAEA TRS 398 protocol; mobile linac Novac-7Irradiation setup: 

7 or 9 MeV 20x20 cm^2 electron beam; full backscatter water phantom at 

SSD 100 cm.The steps of the procedure are: only one 2x13 cm^2 film strip 

positioned vertically (i.e. making the strip long axis coincide to the beam 

axis) is irradiated in a water phantom. The PDD curve obtained from the film 

is compared with the Linac PDD mesured with ionization chamber in order 

to elaborate a film calibration curve. The PDD curve of film is the net optical 

density (NOD) vs depth curve normalized to the maximum NOD. The NOD is 

drawn with scanning the film an office flat bed scanner in transmission mode. 

After the superposition of the maximum film PDD point to the maximum Linac 

PDD point, we observed a very good correspondence between the two PDD 

curves beyond the maximum build-up depth up to the depth of 5% dose.In 

this range of depths we used the film NOD values and the doses from the 

Linac PDD curve to draw the film calibration curve. Finally, a second film strip 

was irradiated, with the same setup, in the IORT beam and a NOD vs depth 

plot was drawn making possible to do beam calibration and verification. 

Results: As expected, the film calibration showed a nice linear correlation 

between NOD and dose (R^2 = 0.9998). 

Conclusions: The method described allows to simplify the radiochromic film 

calibration procedure improving the accuracy minimizing errors due to film 

handling and positioning in the wather phantom at the reference depth. Furthermore, 

the same irradiation modality allows straightforward determination 

of the IORT beam characteristics. 

1189 poster 

A PROCEDURE FOR INVESTIGATING LIGHT AND RADIATION 

FIELD CONGRUENCE USING EPID 

A. Fredh 1 , Palm 2 , G. Sernbo 2 

1 COPENHAGEN UNIVERSITY HOSPITAL, RIGSHOSPITALET, Department of 


2 SAHLGRENSKA UNIVERSITY HOSPITAL, Department of Radiation Physics, 


Purpose: A standalone method to check the congruence of the light field and 

the radiation field at a radiotherapy accelerator using EPID has been developed 

and evaluated. The purpose of the study was to establish a method 

that is easy to use in clinical practice for routine QA instead of performing 

measurements with film. 

Materials: An in-house phantom was developed consisting of a polystyrene 

plate with dimensions 25.1 cm x 25.1 cm x 0.5 cm. A radio-opaque point 

marker was used to locate the center of the field. A radio-opaque square 

made of tungsten was also placed 10 mm inwards from light field edge markings 

corresponding to a 20 cm x 20 cm field. The square marker was used 

in the evaluation of the EPID images to facilitate field size measurements at 

two points for each jaw orientation (to match the results of the automatic film 

evaluation). During the measurement procedure, the light field was aligned 

with the field markings and images were acquired using EPID based on the 

amorphous silicon technique. The measurements were repeated at the same 

geometry but after having placed a film behind the phantom. The field size 

was first determined by measuring the distance between the square marker 

and the radiation field edge on the EPID images using the associated EPID 

software. The film images were scanned with a Vidar VXR-16 Dosimetry Pro 

Scanner and subsequently analyzed with dedicated software (RIT113 V4.3) 

to determine the field size. The EPID and film measurements were performed 

at two different accelerators and the results for the four jaw directions were 

compared for the two methods. The accuracy and reproducibility of the measurements 

were evaluated. 

Results: The mean values (and their SD) of the measured field sizes were 

evaluated for both accelerators and for a sufficiently large number of measurements. 

We compared the results for EPID and film, the emphasis of the 

evaluation being on measurement stability. We found that EPID measurements 

were more robust than film measurements (the SD being 0.03 cm and 

0.04 cm for EPID and film, respectively). It was also found that the sensitivity 

of EPID measurements was about 1 mm. 

Conclusions: We concluded that it is feasible to replace film by EPID in 

routine QA for light/radiation field congruence. The EPID method is as good 

as the film method with an additional improvement on stability. When using 

the EPID method a tolerance of 1 mm is further recommended. 

1190 poster 

ABSOLUTE DOSE VERIFICATION OF DIFFERENT IMRT TREAT- 

MENTS USING TLD DOSIMETERS 

N. Lopez - Vilanova 1 , A. Sanchez-Reyes 2 , A. Vila 3 , M. A. Duch 2 , A. 

Rodriguez Garcia 1 , S. Loscos 1 , M. Ginjaume 2 , A. Pedro 1 

1 


2 

UPC, INTE, Barcelona, Spain 

3 

HOSPITAL PLATO, Barcelona, Spain 

Purpose: To determine the absolute dose in some points inside the treatment 

fields and to compare them with those obtained by the planning system in 

order to provide a quality control for IMRT treatments delivered using the 

slide windows technique (6 MV and 18 MV). 

Materials: The doses from dynamic multileaf collimation fields were measured 

for both 6 MV and 18 MV on a Varian 2100 CD 120 Millenium MLC using 

TLD dosimeters inserted in a RANDO Anderson phantom. The measurements 

were carried out on diverse treatments like prostate, head and neck, 

cranial tumors and breast tumors. Dosimetric planning was calculated by 

using ECLIPSE planning system and HELIOS module in the IMRT planning 

treatments. All treatments were a real patient dosimetric study performed in 

our Radiotherapy Service. 

Results: It has been found a very good agreement between calculated doses 

and experimental TLD doses for all the different treatments. As it can be 

shown in the following table, the differences obtained are lower than 3 %. 

Conclusions: TLD dosimeters provide an easy and simple absolute dose 

quality control on IMRT treatments.This work was supported in part by a grant 

FIS PI06/0394. 

1191 poster 

ACCURACY OF DOSE CALCULATIONS FOR SINUS ETHMOIDALIS 

PATIENTS TREATED WITH HELICAL TOMOTHERAPY. 

B. De Ost 1 , B. Schaeken 2 , D. Van Gestel 1 , J. Goossens 1 , D. Van den 

Weyngaert 1 

1 ZNA, Universitaire Radiotherapie Antwerpen, Antwerp, Belgium 

2 XIOS HOGESCHOOL LIMBURG, Nuclear Technological Centre NuTeC, 

Hasselt, Belgium 

Purpose: In the tomotherapy concept; planning, treatment and individual 

patient QA are part of one integrated system. The purpose of this work is to 

make an independent check of the calculated dose for patients treated for a 

sinus ethmoidalic carcinoma. 

Materials: For QA of individual treatment plans, the ’copy to phantom’ tool of 

the tomotherapy planning system is used: the sinogram is copied to the Alderson 

phantom such that the clinical situation is simulated in the most realistic 

way. Dose measurements are carried out with alanine detectors (Harwell) 

and TLD (Harshaw, pellets) at all points of interest (tumour volume, critical 

structures,&), and compared with the calculated dose. The EPR-signal intensity 

(EMS104, Bruker), measured as the peak to peak height of the central 

line in the absorption spectrum of L-α alanine, varies linearly with dose. The 

alanine dosimeters are calibrated in Co-60. The combined standard uncertainty 

in alanine dose measurement is 2.2% at an absorbed dose of about 

10 Gy. TLD’s are calibrated in 6MeV with an estimated combined standard 

uncertainty of 2.7% at 2 Gy. The phantom was set-up with an MVCT in fine 

mode. The dose administered to the detectors due to this MVCT was taken 

into account when analysing the measured dose. For the evaluation of dose 

calculations, the concept of confidence limit (CL) = | Dcalc-Dmeas| + 1.5 SD 

is adopted in low dose gradient regions and distance to agreement (DTA) in 

high dose gradient regions. The presented results are part of an ongoing 

project; more measurements will be performed to refine the confidence limit 

in tomotherapy. 

Results: Analysing a total of 184 measurements in 8 phantom set-ups: for 

measurements in a low dose gradient region a CL of 4.1% was found with 

alanine, CL is 5.6% with TLD. In high dose gradient region the CL for TLD 

measurements was 8.0% or a mean DTA of 0.74 mm (SD=1.04, N=25). In 

comparison with the step and shoot IMRT (Elekta Sli, measurements with 

alanine) for head and neck patients (N=225); a CL of 7,6% and, in case 

of a number of segments lower than 50, 6.2% were found. When using a


non IMRT, non coplanair 7 beams set-up for sinus ethmoidalis patient on a 

conventional linac, the CL is 3.5% (N=13, measurements with alanine). In 

this case the dose conformity to the PTV is significant lower compared to 

tomotherapy. 

Conclusions: The copy to phantom methodology, in combination with TLD 

and alanine measurements, is found to be a reliable technique to gain confidence 

in complex treatment modalities at our department. Numerous dose 

measurements will allow to establish a tolerance level for the treatment of 

ethmoidalis patients with helical tomotherapy. 

1192 poster 

AN INVESTIGATION OF THE DOSE DISTRIBUTION IN THE 3D 

DOSIMETER PRESAGETM WITH ELECTRON RADIATION. 

R. Hollingdale 1 , S. Doran 2 , A. Nisbet 1 

1 

ROYAL SURREY COUNTY HOSPITAL, Department of Medical Physics, 

Southampton, United Kingdom 

2 

INSTITUTE OF CANCER RESEARCH, Candiolo (Turin), Italy 

Purpose: Presage TM is a novel 3D dosimeter comprised of Polyurethane and 

a leuco malachite green dye. The optical density of the dosimeter changes 

when the dye is exposed to radiation, allowing a 3D view of the dose distribution 

to be seen when read by the optical CT scanner. This study investigates 

Presage TM when irradiated by electrons beams from a linear accelerator. 

Materials: Samples of Presage TM , 6cm in diameter and 6 cm in length, were 

irradiated with 6, 9 and 12 MeV electron beams from a linear accelerator and 

the 3D dose distributions produced read with an optical CT scanner. Due 

to the ability of Presage TM to be machined, identical samples with a 1cm diameter 

and 1cm deep cavity were also produced and irradiated, the dose 

distributions produced were compared to those without a cavity in the sample. 

The samples were also read by the scanner before irradiation to give 

information on background noise. 

Results: It was found that in Presage TM the percentage optical density 

change with depth closely matched the depth dose in a water phantom, this 

was closest at the lowest energy 6MeV where the position of maximum dose 

and optical density varied only by 0.84mm. The effect of the cavity in the 

sample was found to cause a rise in the relative dose deposited in the sample 

below the cavity, by up to 78% compared to when no cavity was present. 

The depth of maximum optical density was also found to decrease due to 

the cavity being present. The background noise of the samples was found to 

vary, with some samples being of poor quality and high noise. 

Conclusions: The dose distribution in Presage TM closely resembled the 

dose distribution in a water phantom and in combination with a CCD detector 

may be an attractive choice for complex 3-Dimensional electron dosimetry. 

1193 poster 

AUTOMATED QUALITY CONTROL OF THE MLC PERFORMANCE 

USING AN ELECTRONIC PORTAL IMAGING DEVICE 

M. De Brabandere 1 , J. Hrbacek 1 , A. Swinnen 1 , F. Van den Heuvel 1 

1 UNIVERSITY HOSPITAL GASTHUISBERG, Radiotherapy, Leuven, Belgium 

Purpose: To check the accuracy of the MLC performance, several tests have 

been developed and presented in literature. Most of these tests require a 

visual inspection of the projected leaf patterns, either using a light-field or 

traditional films. This method carries at least two disadvantages: it is time 

consuming and the evaluation is subject to the individual judgement of the 

performing physicist. We developed an automated procedure for QC of the 

MLC performance using the EPID. 

Materials: In our department 5 Clinac 2100 C/D units (Varian) equipped 

with an aSi EPID and a dynamic Millennium MLC are used. Three imagers 

have an active image acquisition unit of 1024x768 pixels (~40x30 cm2, res 

0.39mm/pix), two imagers have a 512x384 pixel matrix (res 0.78mm/pix). A 

radio-opaque pellet mounted on a plastic holder is placed in the isocentre. 

The pellet projection allows to define the isocentre location on the EPID images. 

Due to the limited size of the image acquisition unit, it is necessary for 

some checks to use multiple imager positions to cover the entire leaf travel 

range. The image information is processed using a Matlab script. Following 

checks are performed: a. Absolute leaf calibration: to verify the positional 

leaf accuracy during static delivery, the leaves cycle through a sequence of 

positions from 20 cm to 20 cm in 5 cm increments with a 5 cm gap between 

the left and right carriages. At each position, the actual distance with respect 

to the isocentre position is checked. b. MLC field radiation centre: checks the 

stability of the rotational axis. The imager is exposed with a centrally located 

field with collimator 0 ◦ , 45 ◦ and 315 ◦ . The centre of the resulting spoke pattern 

should coincide with the isocentre projection. Our MLC code detects the 

field centre based on the irradiated field outline and compares it to the exact 

isocentre position. c. MLC carriage skew: to verify that the MLC is correctly 

aligned with the secondary collimators two leaves are driven to overtravel position. 

Our programme calculates the angle between the protruding leaves 

and the parallel jaws. d. MLC carriage sag: a centrally located field is delivered 

from gantry 90 ◦ and 270 ◦ . The irradiated field centre is traced and the 

deviation with the isocentre location is recorded. e. Picket fence test: to verify 

S 381 

the positional leaf accuracy during dynamic delivery leaf pairs have multiple 

stops at equally spaced positions. A 0.5 mm gap is created between the left 

and right leaves, hence producing a hot spot at the pre-determined positions. 

A fence-like pattern with straight lines is created. Our programme calculates 

the offset between the measured and theoretical line positions. The MLC, 

jaw, collimator and gantry settings as well as the imager positions are programmed 

in subsequent fields of a patient file which is stored in the R&V 

system. The sequence of the fields is optimised to minimise the number of PI 

movements. 

Results: The Matlab program gives a graphical presentation of the acquired 

images, as well as an overview of the deviations, either in graphical or digital 

form. The method was preliminary tested on different treatment units. The 

first results show that the deviations are within 2 mm tolerance for the static 

leaf calibration, and within 1 mm for the leaf gap. The stability of the rotational 

MLC axis was < 1 mm, as well as the MLC carriage skew. The MLC carriage 

sag was < 1 mm. The picket fence test showed no deviations > 2 mm. Reproducibility 

of these results needs to be evaluated over time. Based on this, 

tolerance levels will be defined. Image delivery time takes 20-25 min. Image 

processing and evaluation takes an additional 5 minutes. This is a reduction 

in time to one third compared to the film-based method (60 min checks + 

15 min film development and evaluation). In addition, the MLC check is now 

totally quantitative, objective, and well recorded. 

Conclusions: We developed an automated procedure for QC of the MLC 

performance using the EPID. This method is a fast, accurate, objective and 

cheap alternative for the time-consuming film based QC checks. 

1194 poster 

BRACHYTHERAPY HDR DOSE EVALUATION IN GYNAECOLOGIC 

CANCER TREATMENT USING A RECTAL PROBE WITH ALA- 

NINE/EPR DOSIMETERS 

V. Pinto 1 , R. Pirraco 2 , A. Pereira 2 , T. Viterbo 2 , J. Lencart 2 , L. Pereira 1 

1 UNIVERSIDADE DE AVEIRO, Fisica, Aveiro, Portugal 

2 INSTITUTO PORTUGUÊS DE ONCOLOGIA FRANCISCO GENTIL (CROP), 

EPE, Fisica, Porto, Portugal 

Purpose: The quality control of Brachytherapy treatment delivery is an important 

field of study. Currently, our department does not measure the dose 

delivered at organs at risk, like the rectum in gynaecological High Dose Rate 

(HDR) treatments, and compare it with the values given by the treatment 

planning system (TPS). With the possibility to use alanine as dosimeter, due 

to linear dose response of electron paramagnetic resonance (EPR) signal of 

irradiated samples, a new brachytherapy dose control framework has been 

opened. 

Materials: For gynaecologic HDR Brachytherapy treatments the prescribed 

dose is 7Gy applied with an 192Ir source. The experimental data was collected 

via a rectal catheter with dosimeters located at specified points during 

treatment. A previous calibration curve was made in a dose ranging from 1 to 

30Gy. The calibration curve allows determination of the dose delivered to the 

patient’s rectum. In spite of the traditional reading of peaktopeak intensity of 

central EPR spectrum line of a dosimeter, we perform a spin density calculation, 

taking into account the total EPR spectrum, increasing accuracy. The 

dose was further evaluated by EPR theoretical reconstruction from the experimental 

spectra and considering the calibration curve.Doses determined with 

alanine/EPR method are compared with expected values from the TPS. 

Results: With these results a discussion is made for the possibility of applying 

this technique on a regular basis for measuring radiation doses to the rectum 

in gynaecologic treatment. 

Conclusions: Our work shows a comparison of doses measured to the rectum 

with alanine/EPR dosimeter method with doses calculated by the TPS 

when patients perform gynaecologic HDR treatments. 

1195 poster 

CLINICAL FEASIBILITY OF USING FILM-BASED, IN VIVO DOSIME- 

TRY TO DETECT SETUP ERRORS DURING STEREOTACTIC BODY 

RADIOTHERAPY TREATMENTS USING HELICAL TOMOTHERAPY 

D. Giantsoudi 1 , A. Gutierrez 1 , C. Shi 1 , N. Papanikolaou 1 

1 CANCER THERAPY & RESEARCH CENTER AT THE UNIVERSITY OF TEXAS 

HEALTH SCIENCE CENTE, Radiation Oncology, San Antonio, TX, USA 

Purpose: Film-based, in vivo dosimetry using helical tomotherapy has been 

previously proposed as a simple treatment delivery verification technique. 

Due to the high dose per fraction and low number of fractions, implementation 

of this technique for SBRT treatments may be of benefit to dose delivery 

verification. This study seeks to examine the clinical feasibility and sensitivity 

of film-based, exit dose dosimetry in detecting rigid body shifts and inhomogeneities 

during stereotactic body radiotherapy treatments (SBRT). 

Materials: A QUASARTM respiratory motion phantom (Modus Medical Devices, 

Canada) was CT scanned, in static mode, with an imaging insert containing 

two spheres of different sizes and a cube. A SBRT treatment plan 

was created with TomoTherapy TPS (TomoTherapy Inc, Madison WI) utilizing 

one of the spheres as the target volume. Dose prescription was 98% of


target volume to receive at least 60.0Gy delivered in 5 fractions. The image 

set was imported into tomotherapy TPS as a patient image set for treatment 

planning and as a phantom image set for delivery quality assurance verification. 

Radiographic film Kodak EDR2 (Kodak, Rochester NY) was placed 

at the couch table top below the phantom (coronal plane) during irradiation 

so as to measure the exit dose. Delivery was repeated with the introduction 

of various lateral shifts and inhomogeneities to the phantom. Calculated exit 

dose planes were extracted from the DQA analysis software and compared 

with measured films. 

Results: Agreement between calculated and measured exit dose planes for 

the original setup was shown to be within 10%. This discrepancy may be 

largely associated with the low absolute doses recorded (< 1Gy). However, 

good spatial agreement was achieved. Comparison profiles of the calculated 

and measured exit dose planes between the 2cm lateral shift and original 

setup indicate insufficient sensitivity of the film measurements to distinguish 

the expected differences and patternssee Figure 1. Similar conclusions were 

reached for 5cm lateral shifts as well as when relatively large inhomogeneities 

were introduced. 

Conclusions: Based on preliminary results, film-based, in vivo dosimetry 

may be suitable for lung SBRT dose delivery verification but was shown not 

to be sensitive in the detection of rigid body shifts and inhomogeneities. Further 

studies different treatment sites are planned to determine if film-based, 

in vivo dosimetry can be used as a secondary technique for patient setup 

verification. 

1196 poster 

CLINICAL IMPLEMENTATION OF DAILY IN VIVO MESUREMENTS 

USING MOSFET DETECTORS 

S. Karthikeyan 1 , N. Jornet 2 , P. Carrasco de Fez 2 , F. Garcia 3 , V. A. P. 

Reddy 1 , D. Manigandan 4 , T. Eudaldo 2 , M. Ribas 2 

1 

APOLLO CANCER HOSPITAL, Radiation Oncology, Madras, India 

2 

HOSPITAL DE LA SANTA CREU I SANT PAU, Radiofísica y Radioprotección, 


3 

CENTRO INVESTIGACIÓN PRÍNCIPE FELIPE, Bioinformatics Department, 


4 

ANNA UNIVERSITY, Physics, Chennai, India 

Purpose: In vivo dose measurements during each session are useful to detect 

random and systematic errors in dose delivery. The use of detectors with 

build-up caps to accurately measure entrance dose is not recommended as 

there is a risk to cause a dose reduction in part of the PTV. A method using 

two MOSFETs on the skin of the patient, with and without a cap, is proposed. 

Both are used, one next to the other, on the first day for each of the treatment 

fields. The one used with a cap is calibrated to give entrance dose and 

placed at field centre. The reading and position of the second detector in mV 

is recorded. If entrance dose is within tolerances the reading of the second 

detector is taken as the reference for daily measurements. In case of opposed 

fields the MOSFET without a cap was not moved, i.e. for the second 

field it would be placed at the exit side. This method was tested in a Cobalt 

Unit and can be extended to other units. 

Materials: The steps followed were: calibration and study of the intrinsic 

precision and correction factors, validation of the method in phantoms and 

clinical measurements. A study of the perturbation caused by this detector 

with and without the cap was performed. Calibration and correction factors 

for a set of TN-502-RD MOSFETs were determined with no cap and with two 

hemispherical caps of plastic water (pw) and brass with 1 and 0.6 cm radii 

respectively to give entrance dose. As MOSFET have a limited lifetime Gy, a 

statistical approach to determine the optimal sample size and irradiation dose 

was followed. Uncertainty in entrance dose measurements was calculated 

and tolerance levels were set. Measurements using phantoms of different 

thickness and A/P fields making controlled set-up errors were performed to 

check the sensitivity of the procedure. Measurements on a series of patients 


Results: Distributions of readings of 5 MOSFETs alternately irradiated with 

0.5 Gy and 1 Gy till they became useless were obtained. For both doses the 

distribution was normal, the SD was 1.5% and 0.8% for 0.5 and 1Gy respectively 

and the mean/dose coincided. For calibration purposes a sample of 3 

readings with 1 Gy was considered optimal. The mean was calculated and 

an uncertainty equal to 1.6% was assigned. The correction factors for SSD, 

field size and wedges for the two different caps were equal to unity within uncertainty. 

As the brass cap decreased the dose in a 6% at 5cm depth while 

the pw in 2%, the latter was preferred for patient measurements. Difference 

in response of the bare MOSFET with field size was 35% higher than that 

of an i.c. Similar behaviour was found for SSD and wedges. This is convenient 

for its use as second detector as errors in field size, SSD and wedges 

are easily detected. This second detector, setting 5% tolerance level, detects 

differences in field size of 5% of total area, in 2cm SSD and differences in 

2cm thickness when placed at the exit. The uncertainty on entrance dose 

determination in patients is mainly due to the detector’s intrinsic precision. 

Conclusions: The verification method using a second detector is sensible 

enough to detect errors >5% in daily treatment delivery without compromising 

the dose to the PTV. This study was partially financed by FIS PI041884 and 

UICC grant ICRETT No: ICR/07/054. 

1197 poster 

CLINICAL TRIAL OF A CUSTOMISED PLASTIC SCINTILLATION 

DOSIMETER FOR HDR BRACHYTHERAPY 

J. Lambert 1 , N. Suchowerska 2 , M. Jackson 2 , Y. B. Yin 1 , D. McKenzie 1 , 

S. Law 1 

1 UNIVERSITY OF SYDNEY, School of Physics, Lidcombe, NSW, Australia 

2 ROYAL PRINCE ALFRED HOSPITAL, Radiation Oncology, Sydney, Australia 

Purpose: We have developed a plastic scintillation dosimeter [BrachyFOD TM ] 

for QA of HDR brachytherapy. The sensitive volume is 4 x 0.5mm permitting 

it to be inserted into a urethral catheter to give real time measurements of 

dose. Readout is achieved in less than 0.5 second intervals Clinical trials 

with prostate patients have accrued 12 patients by early 2008. The dosimeter 

performance is promising. Clinical experience has led to modifications of the 

dosimeter design in two key areas: self checking for the integrity of the signal 

pathway and the inclusion of a positive location system. 

Materials: Following ethics and TGA approval, 12 patients have been recruited 

to test the BrachyFOD TM performance in a clinical trial, which commenced 

in 2007. The BrachyFOD TM was located in the urinary catheter in the 

urethra for prostate HDR patients. The measured dose to the urethra was 

compared to the calculated urethral dose as determined by the CT dosimetry 

treatment plan. 

Results: The additional intervention of inserting the BrachyFOD TM into the 

urinary catheter was well tolerated by patients, with no physical difficulties 

encountered for insertion. The extra time taken for insertion was no more 

than 3 minutes. For 70% of patients the measured dose was within 10% of 

the calculated dose. In the remaining cases the measured and calculated 

dose were not in agreement. Although the measured dose in these cases 

may have been real, uncertainty motivated two modifications in the dosimeter 

design. The first was a self checking protocol of the light signal pathway 

enabling us to diagnose and correct for any change in signal propagation 

and coupling. The second was the addition of a radio-opaque marker in the 

dosimeter design , enabling us to accurately locate it relative to the patient 

frame of reference. The constraints of ethics approval for this stage of the 

clinical trial did not permit any changes to the treatment should the measured 

and calculated doses differ. 

Conclusions: The improved design of BrachyFOD TM will give confidence to 

the clinician that the measured dose is sufficiently reliable to support intervention 

in the treatment should departures from the prescribed dose be detected. 

Early results from clinical trials show this dosimeter provides useful 

information, is easy to use and minimally affects the treatment procedure. 

ACKNOWLEDGEMENTS: The authors acknowledge the following funding in 

support of this research: NSW Cancer Council Grant RG-06-02 ARC Linkage 

Grant supported by: Bandwidth Foundation, CMS alphatech, Sydney Cancer 

Foundation.

1198 poster 


DAILY TEST ON DYNAMIC INTENSITY MODULATION RADIOTHER- 

APY USING EPID 

J. Richart Sancho 1 , J. Perez-Calatayud 2 , M. Santos 1 , S. Rodriguez 1 , V. 

Gonzalez 2 , D. Granero 2 , M. Pujades 2 , F. Ballester 3 

1 CLINICA BENIDORM HOSPITAL, Radiation Oncology, Benidorm, Spain 

2 LA FE UNIVERSITY HOSPITAL, Radiation Oncology, Valencia, Spain 

3 UNIVERSITY OF VALENCIA-IFIC, 1st Division of General Surgery, Valencia, 

Spain 

Purpose: It is well know that dynamic or sliding windows IMRT (dIMRT) are 

the most efficient methodology for both dosimetric conformation and practice 

aspects. However strict conditions must be verified on the linac and MLC, 

mainly the leaf speed and positioning. In our Institution more than half of the 

patients are treated with the dIMRT technique. For each patient, a specific 

QA verification is performed: 1) for each field the measured absolute fluence 

with EPID is compared with TPS and 2) all the plan is verified with a small ionization 

chamber in a phantom. Because of the workload dIMRT treatments, in 

addition with the previous QA patient specific tests, a daily test program has 

been developed and applied together with the morning tests. The purpose of 

this work is the presentation of this daily program and the experience in its 

application during more than 1 year. 

Materials: dIMRT is performed on a Clinac 2100 CD (Varian). The EPID (a-Si 

500) is complemented with a dosimetric package in the Eclipse TPS (Varian, 

v 6.5). The daily dIMRT program consists in 5 tests: 1) EPID calibration and 

reproducibility. A 10 cm x10 cm field is measured on the EPID. The measured 

parameters are: center shift AB and GT, Flatness-symmetry AB-GT and EPID 

signal in absolute CU units. 2) PWM Test. Recommended by Varian in order 

to evaluate the electric motor status. 3) Garden Fence Test. (Chui-LoSasso 

1996) Using 2 mm slit, reporting the final individual leaf position using profiles. 

4) Sweeping slip. (Chui-LoSasso 1998, Vieira-Pasma 2002) Using slit value 

of 0.5 cm. Symmetry AB-GT plus absolute CU value are reported. This test 

can appreciate up to 0.1 mm deviations. 5) Leaf Speed Test. (Chui-LoSasso 

1996). The resulted fluence is compared with the TPS predicted one. This is 

evaluated using the gamma test (Low 1998) and the steeped profile is also 

individually reported. 

Results: This program has been applied during more that 1 year. The setup 

and irradiation on the linac take less than 5 min, while the average time 

required for the analysis and reporting is 20 min. All performed test results 

have been in tolerance, same as the QA specific patient verification for the 

158 patients treated up today, always within the gamma criteria 3mm/3% 

Conclusions: The implementation of a daily QA dIMRT program is efficient 

and feasible. Because all the aspects with influence in the dIMRT and measuring 

system are tested, it allows keeping both in a high level of performance 

gives confidence in the application of this technique. All this is possible because 

of the EPID dosimetric capability. 

1199 poster 

DOSE DISTRIBUTION 3D-GAMMA EVALUATION OF DIFFERENT 

SESSION DELIVERIES THROUGH ACTUAL MLC POSITIONING 

D. Brown 1 , A. Fogliata 2 , G. Nicolini 2 , E. Vanetti 2 , A. Clivio 2 , L. Cozzi 2 

1 TOM BAKER CANCER CENTRE, Medical Physics, Calgary, Canada 


Purpose: To evaluate the use MLC log files, which record actual leaf positions 

during delivery of dynamic sliding window IMRT, for reconstruction of 

"treated" dose distributions to be compared with the original plan. 

Materials: IMRT Plans for 18 patients (10 H&N, 3 prostate, 3 breast, 2 cervix 

uteri) were optimized with the Varian Eclipse TPS for a Clinac 6EX equipped 

with a MLC-120 leaves. The MLC log files (DynaLog files) generated by the 

MLC controller for each treatment session were recorded. For every patient, 

Dynalog files from 2 to 5 daily sessions (a mean of 3.7 sessions/patient) were 

analysed. The DynaLog files record the position (in motor counts (mc) with 

a conversion of 512 mc/cm) of each leaf every 50 msec. This information is 

back-converted into MLC steering files importable into Eclipse. These "delivered" 

MLC sequences were then used to compute "actual" dose distributions 

on the original CT dataset using the AAA dose calculation algorithm. Resulting 

dose matrices were analysed through a 3D-valuation (for each patient and 

session), using the original dose-plan as benchmark. Threshold for gamma 

computation were (DTA, DeltaD): (1mm, 1%), (2mm, 2%), and (3mm, 3%). 

Three regions were analysed: the PTV (homogeneous high dose volume), a 

corona of 2 cm around the PTV (high dose gradient volume) and the volume 

encompassed by the 10% isodose. 

Results: Results are summarized as averages over patients and sessions 

to give a general appraisal of the results. Further stratifications were also 

applied. For PTV, average gamma ranged from 0.12±0.06 (3mm, 3%) to 

0.34±0.21 (1mm, 1%). The maximum gamma values exceed 1 only in the 

(1mm, 1%) analysis in a PTV volume smaller than 0.5%. For the dose falloff 

region gamma ranged from 0.09±0.05 (3mm, 3%) to 0.25±0.15 (1mm, 

1%). The maximum gamma exceed 1 only in the (1mm, 1%) analysis in a 

volume smaller than 0.5%. The volume encompassed by the 10% isodose 

presented average gamma from 0.05±0.03 (3mm, 3%) to 0.13±0.08 (1mm, 

S 383 

1%). The maximum, exceed 1 in the (3mm, 3%) analysis (max3D


plan, and a second one performed at the end of treatment. The dosimetric 

plans are based on x-ray images.Several parameters are quantified as a function 

of aplicator displacement measured in the x-ray images obtained before 

and after treatment. The parameters are: dose rate, prescription points dose 

(A points), parametric points dose (B points), Rectum and bladder maximum 

doses.One dosimetric plan was repeated five times to provide confidence intervals 

for the results. 

Results: The results show that bladder maximum dose is the most affected 

paremeter. A variation was also observed for the dose rate, but 

smaller.Displacements observed in this kind of treatment have several origins, 

namely: patient transfer between operating theater table to patient bed; 

internal organ movement, aplicators displacement due to the weight of the 

aplicators themselves.It is important to emphasize that it is not possible to 

evaluate the shift in aplicator position during treatment, since x-ray images 

are performed before starting and after finishing. There is also the possibility 

of an increase in displacement due to the transfer of the patient from the 

treatment bed to the x-ray table to acquire the second set of images. This is 

an extra displacement since the normal procedure does not include a second 

set of images. 

Conclusions: Dose quantification at organs at risk is of major importance in 

brachytherapy treatments. Our results show that evaluation of dose variations 

is essential. 

1202 poster 

DOSIMETRIC VALIDATIONS OF THORACIC RADIOTHERAPY. 

R. Garcia 1 , C. Khamphan 1 , V. Bodez 1 , E. Jaegle 1 , D. Nguyen 1 , M. 

Marguet 1 

1 INSTITUT SAINTE CATHERINE, Physics, Avignon - Cedex 02, France 

Purpose: Thoracic radiotherapy is very complex regarding the important difficulty 

to know the real dose distribution with low density tissues. Calculation 

models quality increases constantly but stay limited while Monte Carlo software 

are not available in routine. Dosimetric validations close to real configurations 

are always of a major importance. Anthropomorphic phantoms and 

film dosimetry are the best ways to study all parameters and help in clinical 

decisions. 

Materials: Anthropomorphic phantoms were specially built to offer three clinical 

situations and two density levels. It helped to simulate conformal and 

modulated plans. A costal target, an isolated target inside lung material and 

a bronchus target in continuity with a mediastinum were built around different 

cuts to place dosimetric films in their middle. The study was based on three 

photon beam energies X6, 8 and 18 MV. Gafchromic/EBT films have been 

chosen to limit its influence in low density materials. films were analysed with 

RIT113 software to display dose distribution matrix. 

Results: The dose distribution inside a target close to the low density material 

is influenced by the presence of the film and evaluated between 3 and 

4 %. The analyses help to know the margins which optimise the irradiation. 

They are established regarding photon energy, lung side, head-feet direction 

but also gantry angles and lung density. The study of one beam shows that a 

2 cm margin would be necessary for extreme conditions. However, values between 

0,7 mm and the maximum needed which can be limited to 1,5 cm. The 

necessary PTV for multiple sessions treatments bring to complex simulations 

because the margins influence the target dose distribution. IMRT appears as 

the main solution to optimise lung tumour irradiation but with the help of a 

strong control of breathing. 

Conclusions: It stays always necessary to well know the real dose distributions 

of the numerous ballistic configurations In a thoracic radiotherapy. IMRT, 

breathing control and IGRT offer a very precise radiotherapy which need to 

be well calculated and also well validated. Anthropomorphic phantoms and 

film dosimetry are the only way to optimise the validation of theoretical simulations. 

Based on real measurements, one can take better dosimetric decisions 

and also buy adapted equipments. 

1203 poster 

DOSIMETRY VERIFICATION OF A COMMERCIAL MONTE CARLO 

(MC) TREATMENT PLANNING FOR ELECTRONS TREATMENT. 

F. Lucio 1 , A. Boriano 1 , E. Calamia 1 , M. Barberis 1 

1 ASO S.CROCE E CARLE, Radiotherapy Department, CUNEO, Italy 

Purpose: The aim of this study has been the commissioning of a commercial 

treatment planning system for electrons beams treatments based on MC 

calculations. 

Materials: The accuracy between the calculations and measurements has 

been evaluated in terms of absolute and relative dose in homogeneous phantom. 

Situations examined included different conditions of SSD, gantry and 

presence of blocks. Other comparisons have been executed in heterogeneous 

phantoms to simulate certain clinical situations. 

Results: The percentage difference between absolute measured dose at 

point of maximum using a Elekta Precise linac accelerator (range of energy 

between 6-15 MeV) and calculated dose with Oncentra Masterplan (version 

3.0) treatment planning, in all situations examined, is always lower at 5%. We 

have found a good agreement analyzing the percentage depth dose using γ 

criteria; comparison have shown that only 5% of points exceed the γ > 1 with 

3%/3mm and 9% of points with 2%/2mm. Bidimensional analysis has been 

perfomed using EBT film irradiated orthogonally on the axis of the been in the 

situation of standard and extended SSD, and rotated gantry. Results show 

that 97.6% meet the γ criteria of 3%/3mm, and decrease to 89.2% when the 

criteria is reduced to 2%/2mm. Analysis of EBT in presence of blocks (rectangular 

block and L block) have showed that the agreement is 87% and 72% 

of points for the two criteria used. Finally the last two situations analyzed in 

presence of heterogeneity (lung and bone) have showed that, in presence 

of lung, the TPS respects the gamma criteria in 95% (3%/3mm) and 90% 

(2%/2mm) of points. In presence of bone the number of points where γ is 

less than one is respectively 69% and 58%. 

Conclusions: The performed analysis show a good agreement between 

measurements and TPS calculated data. It is important note that dimensions 

of voxel is fundamental to obtain an accurate dose calculation. As highlighted 

in other publications a voxel size smaller than 3 mm is recommend in all situations. 

The results obtained with heterogeneity have showed that in presence 

of bone TPS is not so good. This is probably due to the CT-HU calibration 

curve and emphasizes that a correct mapping of HU is essential to calculate 

accurate dose with Monte Carlo TPS. 

1204 poster 

EFFECT OF POLYTETRAFLUOROETHYLENE GRAFT TO DOSE 

DISTRIBUTION FOR PHOTON AND ELECTRON BEAMS 

E. Goksel 1 , M. Okutan 2 , N. Dagoglu 2 , E. Kemikler 2 , B. Sahin 2 , A. Toker 

3 , H. Bilge 4 , E. Darendeliler 4 

1 

CERRAHPASA MEDICAL FACULTY, Radiation Oncology, Istanbul, Turkey 

2 

ISTANBUL MEDICAL FACULTY, Radiation Oncology, Istanbul, Turkey 

3 

ISTANBUL MEDICAL FACULTY, Department of Thoracic Surgery, Istanbul, 

Turkey 

4 

ISTANBUL UNIVERSITY ONCOLOGY INSTITUTE, Radiation Oncology, 


Purpose: Polytetrafluoroethylene (PTFE) (Gore-tex R○) materials are used 

as grafts in a wide variety of applications in surgery and in endovasculer interventions. 

It is mainly used as a support tissue in thoracic surgery after 

chest wall resection. 2mm thick PTFE graft was used after chest wall resection 

for patients referred to Istanbul University Oncology Institue for adjuvant 

radiation therapy. 

Materials: Measurements were performed on a Siemens Oncor linear accelerator 

with 6 MV, 18 MV photon beams and 6, 9, 15 MeV electron beams 

using field size 10x10 cm. A PTW Markus parallel-plate ionization chamber 

was used in central axis of a RW-3 solid water phantom. Measurements 

were made at 100 cm SAD for Photon beams and at 100 cm SSD for electron 

beams. The ionisation chamber was placed 5 cm depth for photon beams 

and R85 depth of each energy for electron beams. First set up was irradiated 

without PTFE and second set up was irradiated after that 2 mm phantom 

was taken from 1 cm depth and 2 mm PTFE was placed instead of phantom. 

The results were compared with presence of a PTFE and absence of 

a PTFE for each energy of photon and electron beams. In addition; set-ups 

were scanned with CT and point doses were compared in central axis on a 

treatment planning system. 

Results: Although there is no significant difference for photon beams between 

set-ups without PTFE and with PTFE the dose increase %0,8 for 6 

MV, increasing reach %14 for 6 MeV electron beams. 

Conclusions: It should be noted that the dose beyond the graft would be 

increased significantly when planned with electron beams after PTFE graft 

reconstruction. This study suggests that when planning with electron beams, 

the area beyond the PTFE graft should be carefully assessed and critical 

organ doses must be evaluated accordingly. We need further studies to evaluate 

the interaction between photon and electron beams and variety of grafts 

used in surgery. 

1205 poster 

ELECTRON BEAM MATCHING FOR MEDICAL LINEAR ACCELERA- 

TORS 

C. Behrens 1 , U. Bjelkengren 1 , W. Ottosson 1 , D. Sjöström 1 

1 COPENHAGEN UNIVERSITY HOSPITAL, HERLEV, Department of Oncology, 

Herlev, Denmark 

Purpose: The flexibility in a radiotherapy department is enhanced if the patients 

can be given the same treatment using any of a set of medical linear 

accelerators without altering the treatment plans. For this to be possible, the 

accelerators must be beam matched. Besides increased flexibility in the daily 

clinical practice, beam matched accelerators also reduces the measurement 

workload during commissioning. The beam matching acceptance procedure 

defined by the vendor is based on relative measurements in limited geometries 

and at specific points. Since the vendor defined criteria are quite benevolent 

it is possible that the criteria are met, even though the accelerators are 

not matched well enough to fulfil the clinically relevant requirements of accu-


racy. The beam matching approach has been widely used for photon beams, 

whereas it is less common for electron beams. Due to fast dose falloff beyond 

a certain range defined by the energy of the electrons a relatively small 

change in energy can have a dramatic effect in the delivered dose to the patient. 

Also, the profiles can be very sensitive to small changes in energy and 

other beam parameters. Thus, it may be more difficult to beam match electron 

beams than photon beams. The aim of this study was to investigate the 

feasibility of the beam match procedure for electron beams. Further, based 

on our data analysis, the objective was to present relevant criteria that can be 

used for adequate beam matching. 

Materials: During a period of nine months, four Varian iX accelerators with 6, 

9, 12, 15 and 18 MeV electron beams were installed in our department. In the 

acceptance procedure the first installed accelerator was used as a reference. 

All accelerators fulfilled the vendor defined fine beam match criteria. During 

commissioning a more extensive set of measurements were carried out, e.g. 

depth doses (dd), inline and crossline profiles at the reference depth, and 

output factors. 

Results: The majority of the normalized dd were matched to within 0.5 mm, 

and all the electron beam output factors were within 1%. As an example 12 

MeV electron beam inline profiles are shown in the figure for four accelerators 

for the 6x6, 10x10, 15x15, 20x20 and 25x25 cm2 applicators. To separate the 

curves the data for the different applicators were normalized at the central 

axis to 96, 97, 98, 99 and 100 %, respectively. 

Conclusions: The beam matching acceptance criteria defined by the vendor 

are not strict enough to guarantee a satisfactory beam match. However, a 

clinical acceptable electron beam match can be achieved using stricter criteria 

and being thorough in the acceptance procedure. 

1206 poster 

EXPERIMENTAL EVALUATION OF A FLATTENING FILTER DESIGN 

FOR A 50KVP CONTACT X-RAY THERAPY UNIT 

J. Mills 1 , C. Fletcher 1 , G. Baugh 1 

1 UNIVERSITY HOSPITALS COVENTRY, Clinical Physics and Bioengineering, 


Purpose: An experimental method was devised to evaluate a flattening filter 

designed for an experimental 50kVp Contact therapy unit using BEAMnrc. 

Materials: Measurements of central axis (CAX) depth dose and field profiles 

were made using MD55 GafChromic film exposed parallel to the incident 

radiation in a purpose built solid water phantom made of WT1 material. 

CAX measurements were used to determine the input energy for Monte Carlo 

(MC) simulations. Then further MC simulations of the field profiles were validated 

with measurement. Two films were each given an exposure of approximately 

60Gy, scanned using a Vidar film scanner and analysed using the 

PTW MePhysto mc2 film analysis software in order to determine the central 

axis depth dose in 0.5mm steps. Field profiles at 2mm depth were extracted 

using a 0.5mm step size across the field. The 50kV X-ray unit was modelled 

in BEAMnrc[ ] with a realistic geometry and a parallel monoenergetic electron 

source of 48keV incident on the tungsten target. DOSXYZnrc[ ] was used to 

produce a central axis depth dose and off axis profiles in water. The specification 

chosen for flattening filter design was that the variation in flatness at 2mm 

depth over 80% of the FWHM should be less than +8% while maintaining 50% 

dose at 6mm and 10% dose at 25mm along the central axis. MC simulations 

were run with flattening filter designs built up using 2 to 5 Aluminium disks 

0.1-0.6mm thick and 2-6mm diameter. The flattening filter design which best 

met the flatness and depth dose requirements was selected for manufacture 

and testing. 

Results: CAX depth dose measurements and off axis measurements at 2mm 

deep agreed well with MC predictions when a 48keV incident electron source 

was used , Figure 1. Measurements of the field profile at 2mm depth with the 

S 385 

test flattening filter showed uniformity that complied with the specifications as 

predicted. 

Conclusions: A rapid measurement method for the evaluation of the radiation 

beam of a low kV unit has been demonstrated. The technique permits 

central axis and full isocontour measurements of the beam. The measurements 

demonstrated the validity of the MC predictions and verified the use of 

MC for a filter design at this energy. 

1207 poster 

FAST, DOSIMETRIC LEAF CALIBRATION USING ELECTRONIC 

PORTAL IMAGING 

E. Roelofs 1 , D. Emans 1 , M. Palacios 1 , A. Dekker 1 

1 GROW U.H. MAASTRICHT, Department of Radiation Oncology (MAAS- 

TRO Physics), Maastricht, Netherlands 

Purpose: Systematic leaf pair offset errors of 2 mm of the multileaf collimator 

(MLC) can lead to significant errors in segmented intensity modulated radiotherapy 

(IMRT) treatments, requiring an intensive quality assurance (QA) 

programme and frequent MLC calibration. To improve the calibration procedure, 

we propose an accurate and fast dosimetric leaf position calibration 

method for Siemens accelerators with an OPTIFOCUS 82 leaf MLC, using an 

OPTIVUE 500 amorphous silicon electronic portal image device (EPID). 

Materials: First, the centre of the EPID is determined by imaging half fields 

using one collimator bank at the central axis and rotating the collimator to 

90 ◦ and 270 ◦ . Then a fence test is performed, which consists of a single 

beam with four IMRT segments creating abutments at positions 10, 0 and 

-10 cm. For each segment, an image is taken with the EPID and the leaf 

positions are automatically determined using in-house developed software. 

The discrepancy between the desired and actual leaf position is then used to 

calibrate the MLC. After correction of the leaf settings, the test is repeated to 

validate the calibration. 

Results: By using a source-to-imager distance (SID) of 120 cm, a maximum 

field size of 30x30 cm 2 can be used to determine individual leaf positions for 

29 leafs with an accuracy of


individual MLC leafs can be obtained. Conventionally, the fence test is only 

performed for gantry angle 0 for which the effect of gravity on the performance 

of the MLC is small. 

Materials: For a number of different separations of the two MLC banks of 

a Varian Millennium MLC, both the sweeping gap test and the fence test are 

performed. The fence dose pattern is acquired with the electronic portal imaging 

device (EPID), facilitating an automatic determination of all leaf positions 

using the image analysis program ImageJ. In addition, the intensity and width 

of the fence pattern are determined automatically from the fence test pattern. 

In order to determine the absolute position of the individual MLC leafs (relative 

to the collimator axis) a fixed asymmetric aperture is mounted on the 

radiation head. With the aperture two EPID images are acquired for collimator 

angle 90 and 270, respectively. The center of the doubled exposed area 

is the intersection of collimator axis with the EPID. The absolute position of 

the individual MLC leafs are determined for gantry angle 0, 90, 180 and 270 

in order to investigate the effect of gravity on the performance of the MLC. 

Results: The digital fence test can within 5-10 minutes determine the leaf position 

of all MLC leafs with an accuracy better than 0.1 mm. This a significant 

improvement in comparison with the standard practice of visual inspection of 

the fence dose pattern on a dose sensitive film, which only provides an accuracy 

of ~0.5 mm. In addition, initial measurements reveal that the intensity 

of the digital fence dose pattern has a very good linear correlation with the 

sweeping gap ratio (R=0.99). Finally, the absolute digital fence test using a 

fixed asymmetric aperture provides an accurate determination of the effect of 

gravity on the MLC motion. 

Conclusions: The digital fence test is a very accurate and fast test for determination 

of all MLC leaf positions. In addition, the leaf separation of the 

two MLC banks can be determined accurately with the digital fence test. As a 

result, all geometric MLC QA for IMRT can be performed only using the digital 

fence test. 

1209 poster 

IN VIVO DOSIMETRY FROM EPID AND MONTE CARLO SIMULATION 

J. N. Badel 1 , C. Ginestet 2 , D. Sarrut 1 

1 CENTRE LÉON-BÉRARD - CREATIS LRMN CNRS UMR5220 - INSERM 

U630, Department of Radiation Physics and Research, Lyon, France 

2 CENTRE LÉON-BÉRARD, Department of Radiation Physics and Research, 

Lyon, France 

Purpose: The dosimetric properties of amorphous silicon electronic portal 

imaging devices (a-Si EPID) make it possible to determine 2D dose distribution 

from a portal image called portal dose image (PDI). Comparison of PDIs 

derived from measured portal images with predicted PDIs can reveal erroneous 

dose delivery to the patient, assuming that patient setup is correct. In 

this study, we propose to simulate a PDI of a given treatment with the MCNPX 

Monte Carlo code in order to compare it, for dose verification purpose, with 

the transit dose through a patient measured with a dose calibrated iViewGT 

ELEKTA EPID. 

Materials: For each given irradiation field configuration (beam energy, collimator 

shape, number of monitor units) the transmission Tpatient(x,y) through 

the patient measured from an EPID in a point (x,y), is defined by the ratio between 

the PDIpatient(x,y) acquired during patient treatment and the PDI0(x,y) 

measured without the patient. Thus, to predict the PDI of a given patient 

treatment, it is necessary to know Tpatient(x,y) and PDI0(x,y). To obtain 

PDIpatient(x,y) we proposed to convert a portal image acquired without the 

patient into a PDI from a home dosimetric calibration process. To obtain Tpatient(x,y), 

a complete Monte Carlo (MC) simulation (accelerator head, patient 

(from CT images), and EPID) of the treatment was performed. Tpatient(x,y) 

was computed as the ratio between the mean deposited energy inside the 

EPID phosphor screen with and without the patient. Measurements were 

performed with the 6 MV photons beam from Elekta Precise linac. Portal 

images were acquired with iViewGT amorphous silicon of Elekta and simulations 

were performed with MCNPX code version 2.5.f. 

Results: In a first time, we have validated the accelerator head simulation. 

Percentage depth dose (PDD) curves and profiles in water tank were simulated 

and compared to measurements. The mean difference between both 

PDDs was less than 1% after maximum dose depth and less than 1.5% in 

build-up region. The mean discrepancy between both profiles dose was less 

than 2% in the region from the beam axis to within 1 cm of the field edge. 

After this validation step, we have evaluated our prediction PDI method for a 

lung tumor treatment. We have computed the transmission through the patient 

in a region of interest (ROI) of 5 x 5 mm on axis from MC simulation and 

experimental measures. The discrepancy between both transmissions was 

less than 0.5%. 

Conclusions: We have proposed a method allowing the prediction of a PDI. 

The method was based both on measured and simulated data. Preliminary 

validations of the treatment head and the predicted transmission showed 

good agreement between measures and computation. Such method can 

serve for treatment verification purpose or, as Monte-Carlo simulation still 

remains slow, to help researchers to develop analytical fast PDI prediction 

method. 

1210 poster 

IN-VIVO DOSIMETRY FOR HEAD AND NECK IMRT VERIFICATION 

USING THERMOLUMINESCENT DOSIMETERS LOADED INTO A 

NASO-OESOPHAGEAL TUBE: THREE YEAR REVIEW 

K. Roxby 1 , F. Gagliardi 1 , J. Crosbie 1 

1 THE ALFRED HOSPITAL, William Buckland Radiotherapy Centre, Mel- 

bourne, Australia 

Purpose: The head and neck intensity modulated radiation therapy (IMRT) 

programme at the William Buckland Radiotherapy Centre was set up in 2004. 

In-vivo dosimetry is carried out using thermoluminescent dosimeters (TLDs) 

inserted into a naso-oesophageal tube for the first fraction of a patient’s treatment. 

The doses delivered are compared to the planned doses on the treatment 

planning system (TPS). Having accumulated data from 39 patients, we 

are now re-evaluating the need for in-vivo dosimetry for these patients. 

Materials: All patients were treated with a 7-field dynamic IMRT plan, 

planned initially using the Plato TPS and from mid-2006 using the Eclipse 

TPS. Twelve lithium fluoride TLD-100 rods were loaded into a nasooesophageal 

tube interspersed with lead markers. A nurse gently guided 

the tube down the patient’s naso-oesophagus, where it remained for the duration 

of the treatment fraction. One anterior-posterior and one lateral open 

field electronic portal image was acquired during patient set up. These were 

used to determine TLD position. The predicted dose at the TLD position was 

determined from the treatment plan. A dose range was also found by examining 

the doses in a small region (1cm diameter annulus) around that position 

and also in the adjacent CT slices. This takes into account the uncertainty in 

determining the exact TLD position. 

Results: Three hundred and three TLD results were considered here. The 

95% confidence interval of the ratio of the measured to the predicted dose 

was (0.974, 0.996). Our measured dose is generally slightly less than our predicted 

dose. This observation is consistent with the treatment planning system 

slightly overestimating the dose within the air cavity (naso-oesophageal 

region). 

Conclusions: In-vivo dosimetry using TLDs inserted into a nasooesophageal 

tube is an easy method of ensuring dose accuracy in head and 

neck IMRT plans. It continues to play an important part in our patient specific 

IMRT quality assurance programme. Given the good agreement between 

measured and predicted doses, we may consider forgoing in-vivo dosimetry 

for the more routine head & neck IMRT cases. 

1211 poster 

IN-VIVO DOSIMETRY IN RADIOTHERAPY: AN IAEA CO-ORDINATED 

RESEARCH PROJECT 

T. Bokulic 1 , A. M. Campos de Araujo 2 , J. Cygler 3 , P. Kukolowicz 4 , S. Luo 

5 , P. Mayles 6 , J. Izewska 7 

1 

UNIVERSITY HOSPITAL "SESTRE MILOSRDNICE", Zagreb, Croatia 

2 

INSTITUTO NACIONAL DE CANCER, Rio de Janeiro - RJ, Brazil 

3 

OTTAWA HOSPITAL REGIONAL CANCER CENTRE, Ottawa, Canada 

4 

HOLYCROSS CANCER CENTRE, Kielce, Poland 

5 

CHINESE CENTRE FOR DISEASE CONTROL AND PREVENTION, MINISTRY 

OF HEALTH, Beijing, China 

6 

CLATTERBRIDGE CENTRE OF ONCOLOGY, Bebington, United Kingdom 

7 

INTERNATIONAL ATOMIC ENERGY AGENCY, Dosimetry and Medical 

Radiation Physics Section, Vienna, Austria 

Purpose: The IAEA has conducted a Co-ordinated Research Project (CRP) 

entitled "Development of procedures for in vivo dosimetry in radiotherapy" in 

2005-2008. The CRP had an emphasis on patient dose studies, both to evaluate 

the clinical value of in vivo dosimetry and to compare different techniques 

for in vivo dosimetry in a clinical setting. Phantom studies to characterize 

dosimeters used in this CRP and to develop the relevant methodology have 

been performed prior to patient studies. The focus was on the dose delivery 

verification at the beam axis (entrance dose). Well established dosimetry 

methods based on TLD and semiconductor diodes have been compared to 

newer devices based on MOSFET and OSL technologies. 

Materials: The investigations have included dosimeter intrinsic characteristics, 

such as energy and angular dependence, fading, non-linearity, dose 

rate dependence, as well as environmental corrections, such as temperature 

dependence, and clinically related corrections, e.g., wedge factors, field 

size dependence, and SSD dependence. Measurement procedures have 

been developed and documented to obtain adequate measurement accuracy 

and precision, e.g., the reproducibility of on-phantom measurements within 

3% (1 SD). A set of build-up caps for various dosimeters needed for patient


dose measurements has been made available through this CRP. Following 

the dosimeter characterization and verification of the methodology for in vivo 

dosimetry on a Rando Alderson phantom, clinical evaluations have started 

with studies of patients treated with Co-60 or high-energy X rays for pelvic tumours, 

head and neck, and breast sites. The accuracy achievable for in vivo 

dosimetry for these sites has been evaluated for a few institutions in developing 

countries and compared to well documented studies in industrialized 

countries. 

Results: Participants have compared TLDs with MOSFETs, TLDs with OSL, 

diodes with MOSFETs, and diodes with OSL in a clinical use. For this purpose, 

simultaneous in vivo dose measurements have been performed on patients 

indicating dosimetry system properties particularly suitable for use in 

specific clinical situations. A set of written guidelines for clinical use of a 

given in-vivo dosimetry system with a list of possible restrictions and special 

considerations has been developed. 

Conclusions: The experience of this CRP may serve as a reference material 

for a radiotherapy centre in a developing country, and may be helpful for the 

selection of the appropriate in vivo dosimetry systems suitable for the local 

conditions in this country. Acknowledgement: In-kind contributions by Landauer 

(OSL), Thomson-Nielsen (MOSFET) and PTW (diodes) are acknowledged. 

1212 poster 

IN-VIVO DOSIMETRY WITH MOSFETS DURING INTRA-OPERATIVE 

RADIOTHERAPY 

J. Penninkhof 1 , J. van Wingerden 1 , J. van Egmond 1 , H. Ceha 2 , P. 

de Haan 2 , A. Verbeek-de Kanter 2 , A. Marinelli 3 , J. van der Sijp 3 , A. 

Petoukhova 1 

1 

MEDICAL CENTRE THE HAGUE, Clinical Physics, The Hague, Netherlands 

2 

MEDICAL CENTRE THE HAGUE, Department of Radiation Oncology, The 


3 

MEDICAL CENTRE THE HAGUE, Surgery, The Hague, Netherlands 

Purpose: The purpose of this study was to investigate the characteristics 

of metal-oxide semiconductor field-effect transistors (MOSFETs) and their 

use for in-vivo dosimetry during Intra-Operative RadioTherapy (IORT). In-vivo 

dosimetry is important for IORT because of the high dose delivered in a single 

fraction. 

Materials: The evaluation of the MOSFETs (Thomson Nielsen TN-502RD) 

consisted of measurement of linearity with dose, reproducibility in time, dependency 

on field size, dose-rate, energy and angular response for electron 

beams in the range of 4-12 MeV. The field perturbation by the MOSFET was 

assessed using film dosimetry. The measurements were performed at a conventional 

linear accelerator (Elekta) and at an IORT dedicated mobile accelerator 

(Mobetron, INTRAOP), in a homemade PMMA phantom at dose maximum. 

In the case of the Mobetron, an action level of 2% is standard for absolute 

dosimetry.During the period October 2007 - February 2008, six patients 

with a rectum carcinoma were treated with IORT while in-vivo dosimetry with 

MOSFETs was done. Calibration of the MOSFET detector was determined 

by measuring the absolute dose with a Roos chamber on the same day. The 

in-vivo dose measurements were performed by attaching the detector under 

the bolus at the end of the applicator. 

Results: At the linear accelerator, the linearity of the MOSFET signal was 

tested for 6 and 10 MeV in the dose range of 1 to 10 Gy and 0.1 to 10 Gy, respectively. 

On the Mobetron, the linearity was checked for 6 MeV in the dose 

range 3-20 Gy. All tests showed a linear behaviour with dose. The dependency 

on dose rate was checked on the linear accelerator for 6 and 10 MeV, 

ranging from 100 to 400 ME/min. The results did not show any influence of 

dose rate. Different MOSFET detectors indicated that the calibration factors 

increase with acquired dose. The effect of field size was relatively small and 

seemed to be exceeded by the dependency on acquired dose. Moreover, 

our data showed that the calibration factor was not strongly dependent on the 

nominal energy (within 2-3 %). The effect of a MOSFET detector on the dose 

in the underlying tissue was less than 2%. The results of in-vivo dosimetry 

are shown in the data table. 

Conclusions: The MOSFET system investigated here is easy to use and 

shows an agreement with the expected dose within 4.4%. 

1213 poster 

S 387 

INFLUENCE OF TREATMENT COUCH ATTENUATION ON DOSE 

DELIVERED BY RAPID ARC TM - VOLUMETRIC MODULATED ARC 

THERAPY MEASURED BY A 2D ION CHAMBER ARRAY 

I. Gomola 1 , T. Depuydt 2 , J. Bocanek 3 

1 IBA DOSIMETRY, Schwarzenbruck, Germany 

2 UNIVERSITY HOSPITALS LEUVEN, Radiotherapy, Leuven, Belgium 

3 VARIAN MEDICAL SYSTEMS INTERNATIONAL AG, Zug, Switzerland 

Purpose: Modern rotational treatment techniques are delivering radiation 

beams to the patients from various gantry angles. The radiation beams are 

attenuated when passing through a treatment couch. The magnitude of attenuation 

depends on the treatment couch design and materials used for its 

construction, beam energy, and gantry angle. Dosimetry impact on the cumulative 

dose distribution predicted by a treatment planning system has been 

evaluated on two different rotational treatment delivery techniques and two 

types of treatment couches. 

Materials: The study was carried out on two different couches: the EXACT TM 

(Varian) with a Clinac 2300C/D (Varian) equipped with the RapidArc option 

and the iBeam TM (Medical Inteligence) in combination with a Clinac 2100C/D. 

The dosimetry measurements were performed with a 2D ion chamber array 

(I’mRT MatriXX TM, IBA Dosimetry) which was inserted into a MULTICube TM 

phantom placed on the treatment couch. The effective point of the MatriXX 

detector was positioned at the isocentre of the treatment delivery system. 

The irradiation in both cases was performed in 6 and 18 MV x-ray beams. 

In this investigations were carried out two sets of measurements. In the first 

set of measurements the irradiations were performed at the gantry angle of 

0 ◦ (AP) and 180 ◦ (PA). The second set of measurements was performed with 

the full arc rotation (360 ◦ ). In case of the EXACT treatment couch the couch 

information were included in the CT phantom dataset prior to a TPS calculation 

(the Eclipse preclinical version of the RapidArc optimizer). In case of 

the iBeam couch the TPS calculation was performed with the ECLIPSE v 7.5 

without added model of the couch. The influence of couch attenuation to delivery 

of clinical IMRT fields (H&N and prostate) and Rapid Arc treatment was 

investigated. 

Results: The EXACT couch beam attenuation has been determined using 

the MatriXX detector array. The most of the attenuation was caused by the 

side couch bars. The maximum beam attenuation of 15% for 6X, and 8% 

for 18X, respectively was found. The Eclipse treatment planning system was 

used to calculate the dose distribution of the single field delivered with and 

without the couch in the beam. The comparison of the dose matrices revealed 

a good agreement of the measured and calculated dose distribution 

with 98% of the values (Gamma criterion 3% / 3mm). The influence of the 

iBeam couch attenuation on accuracy of hybrid plan IMRT QA was investigated. 

For (PA) 180 ◦ , the relative attenuation was found to be 3.5%. For very 

oblique irradiation values up to 7% were observed. 

Conclusions: The influence of the treatment couch should be considered 

into the dose calculations to minimize systematic errors in the dose delivery. 

Our measurements have shown that Eclipse treatment planning system correctly 

models couch influence to the overall dose distribution for static fields 

as well as for Rapid Arc delivery.


1214 poster 

MATRIX IONIZATION CHAMBER BASED DOSE RECONSTRUCTION 

FOR IMRT QA 

E. Korevaar 1 , A. van Hulzen 2 , D. Wauben 1 , P. van der Hulst 1 , H. 

Langendijk 1 , A. van ’t Veld 1 




Department of Neurosurgery, Groningen, Netherlands 

Purpose: Film measurements in phantoms are commonly applied in IMRT 

QA procedures in order to verify the dose distribution calculated by the treatment 

planning system versus the dose delivered at the linear accelerator. 

However, the procedures are labor intensive and results are limited to 2D 

plane(s) without information of patient anatomy. Therefore, we investigated 

a more efficient and at the same time more comprehensive method based 

on matrix ionization chamber measurements and dose reconstruction models. 

For this purpose the MatriXX detector and Compass system (RaySearch 

Laboratories AB and IBA Dosimetry GmbH) were applied. 

Materials: The Compass system consists of a fluence model, a detector 

model, a dose computation model and a method to reconstruct fluence from 

measurements. The fluence model in Compass was configured for the 6MV 

beam of an Elekta Sli linear accelerator, i.e. parameters in a three source 

model such as energy spectrum, spot sizes and scatter source weight were 

determined by fitting computed dose curves to water phantom measurements. 

In the clinical treatment planning system, treatments consisting of 

open fields and MLC test fields were set up to investigate various aspects 

of dose reconstruction, e.g. uniformity and collimation by the MLC at the tip 

and tongue and groove sides. Furthermore, a number of clinical head and 

neck IMRT treatments were selected. The treatments were transferred to a 

homogeneous phantom and exported to Compass and the accelerator. To 

verify the dose reconstruction EBT films were positioned horizontally in the 

phantom and subsequently MatriXX measurements were performed. Reconstructed 

dose distributions were compared to the film measurements after 

conversion to dose. In this procedure the non-uniformity of the applied film 

scanner was handled by a 2D correction function. 

Results: The correction function for the non-uniformity in the flatbed film 

scanner improved correspondence to reference data by locally up to 3%. 

Furthermore, the reconstructed dose in penumbra regions was improved by 

modification of the primary spot size in the fluence model. After these modifications 

a good agreement between measured and reconstructed absolute 

dose distributions in open fields was achieved (within 3%/3mm). The MLC 

test fields showed good accuracy in the high dose gradient regions. Errors 

in MLC position that were introduced on purpose of 1mm could be detected. 

It was found that the results for the clinical head and neck IMRT treatments 

were less sensitive to sub-optimal fluence model parameters than in the set 

of MLC test fields. For these IMRT treatments the percentage of points with 

gamma values > 1 was within 5%. 

Conclusions: With the dose reconstruction method small delivery errors can 

be detected and the effect of these on the dose distribution in the patient can 

easily be visualized and evaluated. 

1215 poster 

MONTE CARLO SIMULATIONS OF CORRECTION FACTORS FOR 

IAEA TLD HOLDERS 

M. Hultqvist 1 , J. M. Fernández-Varea 2 , J. Izewska 3 



2 UNIVERSITAT DE BARCELONA, Facultat de Fisica (ECM), Barcelona, Spain 

3 INTERNATIONAL ATOMIC ENERGY AGENCY, Dosimetry and Medical 

Radiation Physics Section, Vienna, Austria 

Purpose: The standard IAEA TLD holder has been developed for the 

IAEA/WHO TLD postal dose programme for audits of high-energy photon 

beams and it is also employed by the ESTRO-QUALity assurance network 

(EQUAL) and several national TLD audit networks. The holder is a tube made 

of PMMA with an opening at 5 cm from the top in which the TLD is inserted 

during irradiation; it is used for audits in reference conditions. Recently, a 

modified holder has been developed with an opening at 10 cm from the top 

and with a removable horizontal arm enabling TLD measurements off axis for 

audits in both reference and non-reference conditions. 

Materials: In the evaluation of the absorbed dose to water from the TLreadings, 

several correction factors are applied, including one for the influence 

of the holder which is required because the TLD is partially shielded 

by the holder tube. The holder correction is defined as the ratio of the TLresponse 

when the TLD is irradiated without the holder to the TL-response 

when it is irradiated in the holder. The ratios have previously been evaluated 

experimentally and analytically. In the present work, the holder correction is 

evaluated from Monte Carlo simulations with the PENELOPE code for 60 Co, 

6 MV and 18 MV photon beam qualities, on axis for both the standard and 

the modified holder without the horizontal arm. The resulting factors are compared 

to the existing experimental values. In addition, correction factors are 

presented for cases where no values are available. These include irradiations 

with 60 Co and 6 MV photon beams at 10 cm depth in the standard holder, and 

with 18 MV at the same depth in the modified holder. 

Results: The TLD holder correction factors calculated from the Monte Carlo 

simulations are within the experimental uncertainty of previously published 

data. For instance, the factor is 1.006 ± 0.002 (2 SD) for irradiations with a 

60 Co beam and the TLD capsule in the standard holder at a depth of 5 cm, in 

good agreement with the experimental value 1.008 ± 0.006. For irradiations 

at a depth equal to 10 cm, the factor for the same beam quality is 1.006 ± 

0.006 for the standard holder and 1.014 ± 0.012 for the modified one. 

Conclusions: Factors correcting for the influence of the IAEA TLD holder on 

the absorbed dose determined from the TL response have been evaluated 

from Monte Carlo simulations with PENELOPE. The factors have been verified 

against experimental values and factors for situations without previously 

published values have been calculated. 

1216 poster 

ORGAN MOTION CORRECTION WITH PATIENT SHIFTING DURING 

PROSTATE CANCER RADIOTHERAPY: EFFECT ON DELIVERED 

DOSE 

P. Kovacs 1 , Z. Sebestyén 1 , R. Farkas 1 , S. Bellyei 1 , K. Derczy 2 , A. 

Szigeti 1 , G. Liposits 1 , A. Gulyban 3 , O. Esik 1 , L. Mangel 1 

1 UNIVERSITY OF PECS, Institute of Oncotherapy, Pecs, Hungary 

2 UNIVERSITY OF PECS, Department of Radiology, Pecs, Hungary 

3 BORSOD-ABAUJ-ZEMPLEN COUNTY HOSPITAL, Institute of Radiotherapy 

and Clinical Oncology, Miskolc, Hungary 

Purpose: Examining the effect of organ motion correction on delivered dose 

in cases of Intensity Modulated Radiation Therapy (IMRT) and 3D Conformal 

Radiotherapy (3D-CRT) technique during prostate radiotherapy. 

Materials: We used a pelvic phantom to simulate the anterior-posterior organ 

motions at prostate radiotherapy. A hole for an ionisation chamber (IC) 

was created in the centre phantom to allow dose measurements in the representation 

of the prostate. 2 cm air-equivalent material (AEM) was put 2 cm 

below the hole to simulate the rectum. CT scans were taken with 3 mm slice 

increment for irradiation planning with PrecisePlan 2.03 (Elekta, Atlanta GA, 

). The structure set from a real patient was transferred to the phantom, using 

prostate and rectum adaptation to the geometrical parameters. Planning Target 

Volume was delineated according to Radiation Therapy Oncology Group 

(RTOG) 0126 study (2004.). IMRT and 3D-CRT plans were made on the 

grounds of M.J. Zelefsky et al. (Radiother Oncol 2000;55:241-249.), G.O. De 

Meerleer et al. (IJROBP 2000;47:639-648.) and our practice considering the 

dosimetrical constraints of RTOG 0126 study. ±1 cm prostate motion was 

simulated by modifying the position of the IC. It also simulated the changes in 

bladder volume. Rectum volume was also changed by increasing or decreasing 

the extension of the AEM. IC displacement was corrected by shifting the 

phantom. Delivered dose was measured in 7 cases using IMRT and 3D-CRT 

fractions, and single square beams (SSqB): anteroposterior (AP), posteroanterior 

(PA), lateral (LAT). 

Results: The variations from the planned dose in cases of different AEM 

thicknesses and IC positions are shown below.Table: "Dose variations"Dose 

variation is slightly below 1% at IMRT and around 1% at 3D-CRT. It is determined 

by the bladder volume and below of 4.5% at AP SSqB; by rectum 

volume and bladder volume up to 9% at PA SSqB, and around 0,5% at LAT 

SSqB. 

Conclusions: Using either IMRT or 3D-CRT, the effects of organ motion correction 

on delivered dose should be considered when choosing beam directions 

during treatment planning. It is advised to avoid directions nearby PA.

1217 poster 


PATIENT PLAN VERIFICATION WITH DIODE ARRAYS 

S. Riley 1 

1 CLATTERBRIDGE CENTRE FOR ONCOLOGY, Physics, Bebington, Mersey- 

side, United Kingdom 

Purpose: To establish effective methods for patient IMRT plan verification 

using the Delta4 (ScandiDos, Sweden) and MapCheck (Sun Nuclear, Florida) 

diode arrays. 

Materials: MapCheck is a single 22cm by 22cm array of 445 diodes with 

build-up equivalent to 2cm of water. We use it with an in-house rotating 

mounting to measure at different gantry angles. The Delta4 contains three 

arrays with a total of 1069 diodes that are arranged to form two orthogonal 

planes within a 22cm diameter PMMA cylinder. Step and shoot IMRT plans 

for the treatment of prostate, head and neck and mesothelioma tumours were 

verified. The gamma index was used to compare measured and planned 

dose distributions for individual beams. With Delta4 the gamma test was also 

done for the combined dose for the whole fraction. The ability of Delta4 to 

record the dose for each individual IMRT segment was used to investigate 

the variation of dose per MU when the segment MU was reduced and also 

when the same segment occurred at the start, middle or end of an IMRT 

beam. 

Results: Delta4 was used to verify 10 prostate plans and 5 head and neck 

plans. For the whole fraction, greater than 95% of diodes passed a gamma 

test of 3%/3mm for the prostate plans and of 4%/3mm for the head and neck 

plans. When the same IMRT plan was tested on Delta4 at two different beam 

energies, one energy was found to have consistently better agreement between 

planned and measured data. This may be due to a superior beam 

model. A record and verify system error, where the junctions of closed MLC 

pairs were moved from outside the field to within the field, was visible in the 

Delta4 measurements of the individual IMRT segments, although it passed 

the gamma test. With MapCheck it was less easy to see this error although 

the gamma results were poorer than usual. MapCheck was used to verify 

16 head and neck plans and 4 mesothelioma plans. The majority of these 

beams passed a 4%/4mm relative gamma test. Using Delta4 with an artificial 

step and shoot IMRT plan created for the purpose of the experiment, which 

had 2MU segments, we observed variations in the dose per MU of greater 

than 20% between the same 2MU segment delivered at different points within 

the IMRT beam. These segment dose variations are to be confirmed by ion 

chamber measurements. 

Conclusions: Diode arrays are shown to be an effective tool for patient plan 

verification and are capable of highlighting how the agreement of measured 

and planned doses might be improved. 

1218 poster 

PHANTOM FOR TL DOSIMETRY IN BRACHYTHERAPY 

J. Nilsson 1 , M. Lundell 1 


Purpose: Investigate the influence of heterogeneities in the treatment region 

for high dose rate HDR (Ir192) brachytherapy (BT) by constructing a phantom 

for Thermoluminescent Dosimetry (TLD) measurements. 

Materials: In BT the treatment plan is a very complex composition of many 

source positions in different needles, catheters or applicators. Many sites are 

measuring the source activity and maybe the dose distribution around one 

source position. In this phantom a real treatment situation could be verified 

and the impact of heterogeneities i.e. air cavities could be measured and 

compared to the treatment planning system (TPS) which does not take heterogeneities 

into account. The phantom is composed of Superflab from Mick 

Radio Nuclear Instruments, USA. The boards are placed on top of each other 

and between solid water blocks to create a large homogeneous phantom for 

real BT situations. Between the soft superflab material different applicators 

could be placed to create a treatment situation. Markers for determining the 

position of organs at risk could be placed in the phantom. Pieces of the superflab 

material could be cut away in order to simulate an air cavity in the 

treatment region. The phantom is scanned in a CT and the images are export 

to the TPS where the target is defined and a treatment plan created. TL 

rods or discs are placed into the phantom at exactly the same positions as the 

markers to be able to compare the dose from the TPS to the actual delivered 

dose. To verify the set up of the procedure a prostate treatment was delivered 

including fourteen needles placed by a template into the phantom and 

a catheter including TL rods was passing through the phantom to simulate a 

urethra. 

Results: When there were no air cavities present the agreement between the 

doseplan and the TLDs was within 5%. When introducing a small air cavity 

in the phantom the dose to the TLDs increased to >15% compared to the 

doseplan. The larger cavity the larger discrepancy. 

Conclusions: The results show that it is important to be aware of air cavities 

within the treatment volume in BT. In clinical practice you might get much 

higher doses than expected in specific areas. This concerns both small inhomogeneities, 

e.g. the urethra, and larger ones, e.g. mouth cavity. This might 

induce unexpected side effects of the treatment. 

1219 poster 

S 389 

PHOTON BEAM MATCHING AND THE ACCURACY OF A TPS FOR 

MEDICAL LINEAR ACCELERATORS 

D. Sjöström 1 , O. Wiviann 1 , U. Bjelkengren 1 , C. Behrens 1 

1 COPENHAGEN UNIVERSITY HOSPITAL, HERLEV, Department of Oncology, 


Purpose: The flexibility in a radiotherapy department is enhanced if the patients 

can be given the same treatment using any of a set of medical linear 

accelerators without altering the treatment plans. To make this possible the 

accelerators must be beam matched. Besides increased flexibility in the daily 

clinical practice, beam matched accelerators also reduces the measurement 

workload during commissioning. The beam matching acceptance procedure 

defined by the vendor is based on relative measurements in limited geometries 

and at specific points. Since the vendor defined criteria are quite benevolent 

it is possible that the criteria are met, even though the accelerators are 

not matched well enough to fulfil the clinically relevant requirements of accuracy. 

The purpose of this study was to investigate whether it is sufficient 

to use only one set of photon beam data in the treatment planning system 

(TPS) to characterize all eight linear accelerators. Further, based on our data 

analysis, the objective was to present relevant criteria that can be used for 

adequate beam matching 

Materials: During a period of nine months, eight Varian iX accelerators with 

6 and 15 MV were installed in our department. In the acceptance procedure 

the first installed accelerator was used as a reference. All accelerators fulfilled 

the vendor defined fine beam match criteria. During commissioning a more 

extensive set of measurements was carried out, e.g. depth doses (dd), point 

doses, profiles, and 2D array measurements. Input data for theTPS, Eclipse, 

was only measured for the reference accelerator. The measured data for all 

accelerators were compared with calculated data from the TPS and/or the 

reference accelerator. Open beams as well as enhanced dynamic wedged 

beams were evaluated. The data were analyzed using the gamma index, 

distance-to-agreement (DTA), and/or local percentage dose deviation (LPD). 

Results: The majority of the comparisons between measurements and TPS 

calculated absorbed dose data fulfilled the criteria 2% LPD, 2 mm DTA and/or 

2%/2 mm gamma index for open beams. For wedged beams the corresponding 

evaluation was 3% LPD, 2 mm DTA and/or 3%/2 mm gamma index. In 

the figure the deviation between Eclipse calculated and the measured dd for 

all eight accelerators are shown for two field sizes. The figure illustrate that 

the deviation for all data points and all accelerators are within the TPS acceptance 

criteria, but also that the mutual deviation between the accelerators are 

less than 1%. 

Conclusions: It is adequate to use only one data set in the TPS to achieve 

similar accuracy for all accelerators. The beam matching acceptance criteria 

defined by the vendor are not strict enough to guarantee an optimal beam 

match. Deviations between all accelerators are, for most data points, within 

1% and/or 1 mm for both open and wedged beams.


1220 poster 

PRE-TREATMENT VERIFICATION OF INTENSITY MODULATED 

BEAMS USING TRANSIT DOSIMETRY 

M. Litoborski 1 , J. Litoborska 1 , E. Licznerska 1 , S. Adamczyk 1 , M. 

Kruszyna 1 

1 GREATPOLAND CANCER CENTRE, Medical Physics Department, Poznan, 

Poland 

Purpose: Portal Dosimetry has become widely used for pre-treatment verification 

in intensity modulated radiotherapy (IMRT). The values which are 

compared are fluences: the predicted with the acquired. The gamma method 

is used to evaluate results after measurements. The aim of this study is to 

show author’s results of portal measurements and investigate errors during 

daily pre-treatment verification. 

Materials: For this study Varian equipment was used: Eclipse treatment 

planning system with Portal Dose Image Prediction algorithm. Total number 

of 403 patients treated using IMRT (Sliding Window) were included into 

the study. The authors-defined acceptance criteria for gamma evaluation 

were 3% for dose-difference and 3 mm for distance-to-agreement. During 

the gamma evaluation the score value shows how many points meet the requirements. 

The authors decided to accept results for which score value was 

not less than 95%. 

Results: Two groups of patients were analyzed. The first group included 

234 patients undergoing IMRT for pelvic region cancers and second group 

included 169 patients with localized head and neck cancers. The first group 

was treated with photons 20 MV, the second one with photons 6 MV. For 

the first group the mean gamma value was 0.27 ± 0.15 SD and the mean 

score 97.79% ± 3.38 SD, for the second group the mean gamma was 0.21 

± 0.10 SD and the mean score 99.00% ± 1.40 SD, respectively. For the 

1st group (pelvic) 143 fields exceeded gamma criteria, while in the 2nd group 

(head and neck) only 32 field did not meet the criteria. The errors were detected 

for the fields with large dose gradient at the edges. In some cases 

the calibration of electronic portal imaging device (EPID) older than 2 weeks, 

had large influence on errors. Also images acquired at larger distances from 

central axis showed deviations and usually exceeded the authors-defined acceptance 

criteria for gamma evaluation. In this study errors were found in 

patient isocenter localization, jaws position compared to the leaves being at 

the field edges and also for parameters X-smooth and Y-smooth which are 

set during optimization process. 

Conclusions: Portal Dosimetry is an accurate method of pre-treatment dose 

verification. It detects errors which can be eliminated before the patient treatment 

begins. In comparison to other methods: films or ion chambers matrix, 

Portal Dosimetry uses one digital system and is easy to perform and significantly 

faster. 

1221 poster 

PRELIMINARY STUDY ON SIMULATING 3D ORGAN MOTION 

ACCORDING TO THE RETROSPECTIVE IRREGULAR BREATHING 

SIGNAL 

S. Lim 1 , T. S. Jeung 1 , S. Lee 2 , S. H. Lee 3 , D. Shin 4 , H. D. Huh 5 , S. J. 

Cho 6 , S. H. Park 7 , S. D. Ahn 7 

1 

KOSIN UNIVERSITY GOSPEL HOSPITAL, KOSIN UNIVERSITY COLLEGE 

OF MEDICINE, Department of Radiation Oncology, Busan 602-702, Korea 

Republic of 

2 

COLLEGE OF MEDICINE, KOREA UNIVERSITY, Department of Radiation 

Oncology, Seoul 136-701, Korea Republic of 

3 

KYONGGI UNIVERSITY, Department of Medical Physics, Suwon 443-760, 


4 

NATIONAL CANCER CENTER, Research Institute and Hospital, Seoul, 


5 

COLLEGE OF MEDICINE, INHA UNIVERSITY, Department of Radiation 

Oncology, Incheon, Korea Republic of 

6 

DONGUK UNIVERSITY, Department of Radiation Oncology, Ilsan 100-715, 


7 

ASAN MEDICAL CENTER, UNIVERSITY OF ULSAN COLLEGE OF MEDICINE,, 

Department of Radiation Oncology, Seoul 138-736, Korea Republic of 

Purpose: The objective of this study is to see the feasibility of simulating 

irregular motion of organ in three dimensionally to be used for dosimetry of 

4D radiation therapy. 

Materials: A moving phantom was designed to move in three directions according 

to the irregular breathing signal. The retrospective breathing signal 

from the control computer transmitted to the 3D moving phantom in which 

GafChromic EBT film was inserted. The wireless Bluetooth signal allows the 

computer to control the remote phantom. Volunteers breathing signal and 

fluoroscopic movies were recorded by simulator (Acuity, Varian Medical Systems, 

Palo Alto, USA). The phantom with the film was irradiated as the 4D 

treatment planning for gated radiotherapy. The 3D motion of the phantom 

was compared with the patient’s organ motion in fluoroscopic movies to see 

the feasibility of the phantom. Residual motion kernel was acquired by deconvoluting 

the radiochromic image of moving phantom exposed with gated 

radiotherapy and the image in the static phantom exposed with non-gated 

radiotherapy. 

Results: The ten patient’s organ motion and the phantom motion agreed with 

more than 0.9 of correlation coefficient. The residual motion kernel was less 

than 5% of the organ motion when the gated radiotherapy was performed. 

Conclusions: The simulating phantom with simulating irregular organ motion 

was feasible to estimate the 4D radiation therapy such as gated radiotherapy. 

1222 poster 

QUALITY ASSURANCE OF ADVANCED RADIOTHERAPY TECH- 

NIQUES WITH DELTA4 

P. Mayles 1 , S. Elmer 1 , H. Mayles 1 , G. Nilsson 2 , S. Riley 1 , J. Shakeshaft 

1 

1 

CLATTERBRIDGE CENTRE FOR ONCOLOGY, Physics, Bebington, Merseyside, 


2 

SCANDIDOS AB, Uppsala, Sweden 

Purpose: Advanced techniques such as gated radiotherapy and Single Arc 

IMAT present additional challenges for quality assurance. Delta4 (Scandidos 

AB) is particularly suited to dealing with these challenges. 

Materials: Delta4 is a cylindrical phantom containing two orthogonal arrays 

of diodes which was designed as part of the EU funded project Invorad. A 

trigger pulse from the linac allows synchronisation of the measurement with 

the linac pulse and the field. For gated radiotherapy a moving platform has 

been built that allows the Delta4 phantom to be moved to simulate the movement 

of a thoracic tumour. The movements can be programmed to conform to 

tumour movements recorded during fluoroscopy for real patients. The quality 

assurance of IMAT is particularly challenging because of the many parameters 

that are varied during the rotation of the gantry. Because Delta4 is a 

three dimensional array of diodes it is particularly well suited to the quality 

assurance of this technique. For rotational therapy an additional angle transducer 

is applied to the gantry in order to relate the dose measurement to 

the treatment. Several Rapid Arc TM plans produced by the Eclipse planning 

system (Varian Medical Systems) have been measured with Delta4 and were 

delivered to the phantom several times to verify reproducibility of the delivery. 

Results: Early results of using the gating phantom suggest that gating can 

be achieved accurately. Further investigations are under way to measure 

the effect of movements on both IMRT treatment and conventional conformal 

treatment. Measurements of Rapid Arc treatment delivery show that it is as 

accurate as step and shoot IMRT achieving >96% of measured points within 

3% or 3mm. It is necessary to include the treatment couch in the calculation to 

achieve the best possible results. Delta4 offers the possibility of assessing the 

accuracy of delivery at different gantry angles and, by the design of particular 

geometric target volumes, to evaluate potential failure modes. 

Conclusions: Delta4 is a versatile and effective tool for quality assurance of 

advanced radiotherapy and provides an ideal solution to the quality assurance 

of modulated arc therapy. G. Nilsson is President and CEO of Scandidos AB. 

1223 poster 

QUALITY ASSURANCE OF TOMOTHERAPY (HI-ART) USING 

GAFCHROMIC EBT FILMS AND A FLAT-BED SCANNER 

F. Cremers 1 , E. Thom 1 , D. Albers 1 , T. Schönborn 1 , C. Grohmann 1 , R. 

Schmidt 1 , M. Todorovic 1 

1 UNIVERSITY-MEDICAL CENTER HAMBURG, Department of Radiotherapy 

and radio-oncology, Hamburg, Germany 

Purpose: Quality assurance (QA) according to TomoTherapy Inc. requires 

a radiographic film (EDR-2 or X-Omat V) in connection with a film developing 

device the QA program Film Analyzer Software by TomoTherapy 

Inc. and a 16-Bit digitizer by VIDAR (DosimetryProAdvantage). There are 

high costs and disadvantages involved for therapy centers which switched 

to radiochromic films (GafChromic EBT) or don’t have films at all. At the 

University-Medical Center in Hamburg IMRT verification is routinely performed 

using radiochromic films (GafChromic EBT). Radiochromic films have 

the advantage that they don’t have to be developed, a calibration is therefore 

only for different lot numbers necessary. They can be handled at room light 

and are tissue equivalent, which can be used for dosimetric purposes. In this 

study QA of tomotherapy (machine QA and patient QA) using EBT films and 

a flat-bed scanner will be shown. 

Materials: For the machine QA the irradiated films were digitized (Epson 

Expression 10000XL, Microtek ScanMaker8700). The generated image format 

48 RGB TIFF was converted to the VIDAR specific format (self-written C 

program) and could then be analyzed by the Film Analyzer Software, which 

contains routines for QA.For the verification of patient irradiations methods 

used to verify "conventional" IMRT irradiations were adopted. The tomotherapy 

treatment plan (TP) is transferred to a cylindrical solid-water phantom 

(Cheese phantom, 30 cm diameter, 18 cm length). The irradiation of the 

film is performed in either a coronal or sagittal plane of the phantom. In the 

phantom drillings allow for simultaneous dose measurements with ionization 

chambers. The film is digitized with a flat-bed scanner and the measured 

data are compared with the treatment planning data using self-written Mat- 

Lab routines.


Results: QA tests requiring film can be performed without a developing process. 

Deviations can be recognized at once. The results of the patient verification 

will be shown. To identify small dose differences the dose scaling was 

enlarged by a factor of 10. The measured and planned dose distributions are 

in good agreement (within a few %). Only in regimes of steep dose gradients 

the deviations are larger. 

Conclusions: Quality assurance of a tomotherapy system (machine and patient 

QA) is possible with GafChromic EBT and a flat-bed scanner instead of 

using a radiographic film and a VIDAR scanner. 

1224 poster 

QUALITY CONTROL OF THE SELECTSEED 125I INTERSTITIAL 

BRACHYTHERAPY SEED 

C. C. Alves de Oliveira 1 , M. D. C. Lopes 2 , A. Matos 1 , J. Perez-Calatayud 3 

1 

INSTITUTO PORTUGUES DE ONCOLOGIA DE COIMBRA, Medical Physics, 

Coimbra, Portugal 

2 

INSTITUTO PORTUGUES DE ONCOLOGIA DE COIMBRA, Coimbra, Portugal 

3 

HOSPITAL CLINICA BENIDORM, Benidorm, Spain 

Purpose: To investigate the reasoning for the deviations between the air 

kerma rate (Sk) value for Isotron I-125 seeds and the measured ones at 

IPOC-FG, EPE, in our clinical routine. 

Materials: 125I seeds (selectSeed) are delivered in a cartridge together with 

a delivery certificate. No clear information on the associated uncertainty or 

traceability is reported. In each prostate implant a QA seed is measured 

with a SourceCheck, type 34051, associated with a UNIDOS E electrometer, 

both from PTW Freiburg. The system calibration factor for the selectSeed is 

1.091x1012±4% YGym2h-1A-1. The combined uncertainty assigned to the 

measured Sk value is ±4.13%. The measured value is compared with the 

nominal one given in the delivery certificate. In order to collect more data, 

pos-implant measurements have been done using 160 unused seeds, from 

9 different seed cartridges. In order to check the calibration factor assigned 

to the measurement system, a calibration seed was requested from Isotron. 

It was delivered on February 22, 2008 with two calibration certificates (NIST 

and Isotron) and was measured using the above mentioned system. 

Results: For the 160 measured seeds we have obtained: an Sk value that 

differed from the nominal one, on average, by -3.66%±1.06%; the measurements’ 

interval ranged from -11.1% and +5.74%; in 46.43% of the cases the 

percentage differences were lower than -4% and in 3.57% they were higher 

than 4%. Regarding the calibration seed, taking into account the decay time, 

the Isotron reported SK value is 3.19% higher than the NIST calibration value 

while our measurement for this calibration seed stayed 3.99% below the NIST 

value. 

Conclusions: The result obtained with the calibration seed may indicate that 

Isotron overestimates the seeds Sk value and delivers seeds at the lower limit 

of the requested class, or even in the class below. An independent measurement 

of this calibration seed is about to be done at Clinica Benidorm (Spain) 

in order to clarify our deviation from NIST value. After that procedure a correction 

to the calibration factor assigned to our measuring system should be 

considered. If our system calibration factor was increased by 3.99% (coming 

to 1.135 instead of 1.091) then from our set of 160 measured values the 

average percentage deviation would rise to 0.15±1.06%. Nevertheless we 

can stress that in 50% of the measured seeds, Sk values were beyond the 

±4% interval claimed by Isotron. More complete information from Isotron 

traceability and uncertainty is required. 

1225 poster 

RADIOCHROMIC FILM DOSIMETRY WITH FLATBED SCANNERS: 

A FAST AND ACCURATE METHOD FOR DOSE CALIBRATION AND 

UNIFORMITY CORRECTION WITH SINGLE FILM EXPOSURE 

L. Menegotti 1 , A. Delana 1 , V. Vanoni 2 , A. Martignano 1 

1 HOSPITAL S. CHIARA, Medical Physics, Trento, Italy 

2 HOSPITAL S. CHIARA, Radiotherapy, Trento, Italy 

Purpose: Film dosimetry is an attractive tool for dose distribution verification 

in intensity modulated radiotherapy (IMRT). A critical aspect of radiochromic 

film dosimetry is the scanner used for the readout of the film: the output needs 

to be calibrated in dose response and corrected for pixel value and spatial 

dependent non-uniformity caused by light scattering; these procedures can 

take a long time. A method for a fast and accurate calibration and uniformity 

correction for radiochromic film dosimetry is presented: a single film exposure 

is used to do both calibration and correction. GafchromicTM EBT films were 

read with two flatbed ccd scanner (Epson V750 and 1680Pro). 

Materials: The accuracy of the method is investigated with specific dose 

patterns and a IMRT beam. The comparisons with a 2D array of ionization 

chambers using a 18 x 18 cm2 non modulated beam and an inverse pyramid 

dose pattern show a better agreement for the corrected films (gamma index 

analysis 3mm 3%). Application to a IMRT beam also shows better gamma 

index results. The number of points and dose range considered for correction 

and calibration appears to be appropriate for use in IMRT verification. 

S 391 

Results: The comparisons with PTW 2D Array Seven 29TM ionization chamber 

array showed that uncorrected films present differences that become 

higher the more the off-axis distance of the considered points; this artifact 

is of different magnitude in the two scanners, but can be well approximated 

by means of a 2nd order polynomial fit in both cases, with coefficients depending 

on the pixel value. Gamma index analysis between scanned films 

and 2D array measurements was performed. The corrected films showed 

a very good agreement with ion chamber array measurements; the agreement 

is comparable for the two scanners. As the artifact effect magnitude is 

different in the two scanners, the method is able to correct properly in both 

situations. 

Conclusions: The single film exposure reduces dose verification time, and 

the agreement between the corrected films and ion chamber array measurements 

makes radiochromic films an accurate and fast tool to perform dose 

verification. The method has been adopted in our clinical routine for IMRT 

dose verification in both transverse and coronal planes, and it showed to be 

fast and accurate, and has been adopted in IMRT dose verification clinical 

routine. 

1226 poster 

RESULTS OF PRACTICAL IMPLEMENTATION OF FILM DOSIMETRY 

FOR IMRT PLAN VERIFICATION 

A. Walewska 1 , W. Bulski 1 , K. Chelminski 1 , P. Kaminski 1 , J. Rostkowska 

1 , M. Kania 1 , M. Zalewska 1 , I. Markiewicz 1 , P. Grochowska 1 

1 THE MARIA SKLODOWSKA-CURIE MEMORIAL CANCER CENTER, Medical 

Physics Department, Warsaw, Poland 

Purpose: The aim of this study was evaluation of results of IMRT plans verification. 

The absolute film dosimetry as well as the ionization chamber point 

dose measurement procedure for total planned dose distribution was evaluated. 

The gamma evaluation concept was used for processing the plan 

verification results. 

Materials: More than 200 IMRT plans were verified using CarPet phantom 

(ESTRO Quasimodo project). The plans, mainly for head/neck and pelvic 

regions, were generated using Eclipse (Varian, Paolo Alto, USA) treatment 

planning system. Field settings and numbers of monitor units were copied 

from the patient plan to the phantom CT images and the dose distributions 

were recalculated. Kodak EDR2 films were placed inside the phantom. The 

films in the phantom were irradiated using all fields of the plan for recording total 

absolute dose distribution. For each plan the measured and the calculated 

dose distributions were compared using in house developed software IMRT- 

Compare. Two methods of calculation of the gamma factor, implemented in 

the software, were compared: Depuydt and in-house developed (INH). The 

3 mm in spatial domain and 3 % of the planned isocenter dose was taken 

as parameters for the gamma evaluation. The fraction of points passing the 

gamma < 1 criterion from rectangular region embedding the 80 % isodose 

was recorded for each plan. 

Results: For the calculation algorithm proposed by Depuydt, in about 75 % 

of evaluated plans the fraction of points for which gamma index value < 1 was 

more than 95 %. For the INH algorithm in about 60 % of cases the fraction 

of passing points was more than 95 %. The fraction of plans for which more 

than 95 % of points pass the gamma < 1 criterion remains stable over the 

time for both algorithms. 

Conclusions: Using different software or different calculation algorithm may 

influence the results of verification. Therefore, the acceptance criteria should 

be evaluated individually for the laboratory depending on the used equipment. 

Cases which fails the verification shows that there is still a need for pretreatment 

dosimetry performed for each IMRT plan. The use of EDR2 films preserving 

the same processing method allows for remaining the acceptance 

criteria unchanged during long period of time. 

1227 poster 

SENSITIVITY TO LUNG PATIENT POSITIONING ERRORS OF EPID 

"IN AQUA VIVO" DOSIMETRY 

L. McDermott 1 , M. Wendling 1 , A. Mans 1 , M. van Herk 1 , B. Mijnheer 1 

1 NETHERLANDS CANCER INSTITUTE-ANTONI VAN LEEUWENHOEK HOSPI- 

TAL, Radiation Oncology, Amsterdam, Netherlands 

Purpose: EPIDs can be used to derive dose information in 3D in vivo from 

treatment (transmission) images, however typically this assumes the patient 

is in the planned position. If the patient is in a different position, due to error or 

intended re-alignment (e.g. organ motion compensation/base line variation), 

then the radiation will go to a different place and the dose distribution may 

change from the planned dose. Whether or not EPID dosimetry picks up this 

change depends on the difference in transmitted radiation for each field. The 

aim of this study was to find the direction and magnitude of shifts for which 

an alert would be raised, based on our new EPID dosimetry method. 

Materials: An anthropomorphic thorax phantom was irradiated with 1 AP 

10cm 2 field and 2 IMRT patient plans (see table). For each irradiation, the 

phantom was shifted in 3 orthogonal directions (0.51.0cm steps). Based on 

EPID transmission images per field, the absolute dose was reconstructed in-


side the patient, in 2D for the AP field and 3D for IMRT plans. The dose 

was compared without inhomogeneity corrections, by using the "in aqua plan" 

(plan calculated with inhomogeneity correction "off") and the "in aqua vivo" 

EPID dose (reconstructed from EPID images, multiplied by the ratio of "in 

aqua" and original plan transmission images). γ statistics within a 50% isodose 

surface (of isocentre dose) were combined in a variable: Γ=[γmean/0.5 

+ γmax1%/2.0 + Pγ>1/3%]/3, where denominators are the alert criteria for 

each parameter. The shift for which Γ=1 (alert is raised) in each direction was 

recorded. 

Results: For verification in 2D (AP field), an alert was not raised until the 

isocentre was shifted 13.1cm anterior or 17.6cm posterior. The planned 

isocentre dose increased by 47% when re-planned with an 18cm posterior 

shift. Displacement in the plane perpendicular to the beam raised an alert after 

0.2 to 1.2cm. For verification in 3D (all fields, 2 IMRT plans), translations 

in any direction raised an alert after 1.2 to 1.9cm, except for shifts along the 

mediastinum (AP direction ) for the 3rd plan, whereby the transmission did 

not change (see table). 

Conclusions: EPID in aqua vivo dosimetry raises an alert for positioning 

differences of ~1-2cm for typical lung cancer treatment plans. If the transmission 

changes for enough fields, positioning changes will be detected. If 

the transmission does not change, despite large shifts, EPID dosimetry will 

not detect a difference. Most lung treatments consist of multiple beams and 

would therefore be sensitive to 1-2cm shifts. 

1228 poster 

STUDY ON THE ACCURACY OF TARGETING ACCORDING TO THE 

PHASE OF MOVING PHANTOM 

C. Min 1 , W. Chung 1 , S. Shim 1 , S. Lee 2 , S. Lim 3 , G. Kim 1 

1 

KONYANG UNIVERSITY HOSPITAL, Radiation Oncology, DaeJeon, Korea 

Republic of 

2 

KOREA UNIVERSITY COLLEGE OF MEDICINE, KOREA UNIVERSITY 

HOSPITAL, Radiation Oncology, Seoul, Korea Republic of 

3 

KOSIN UNIVERSITY GOSPEL HOSPITAL, Radiation Oncology, Busan, Korea 

Republic of 

Purpose: The steraotactic radiosurgery is applied to the whole body as well 

as cranium recently. In this study, the accuracy of targeting according to 

the various phases of the moving phantom was investigated by using the 

Syncrony for tracking the moving tumor with considering respiratory motion. 

Materials: The Syncrony phantom was scanned as width of 1.5 mm with 16 

channels CT (MX8000 IDT CT, Philips, USA) for treatment planning. The 

scanned CT images were used for isocentric conformal treatment planning 

using MutiPlan (Accuray, USA). The prescribed dose was 24 Gy per one 

fraction and the maximum dose was 30 Gy. Two sheets of GafChromic film 

(MD-55, Hay Manufacturing Service, USA) were placed in the cubic box of the 

Syncrony phantom with crossing each other. The photon beams of 6 MV were 

irradiated by tracking the moving Syncrony phantom with 1 second of phase. 

The exposed films were digitized by the flat bed scanner (Perfection V700 

Photo, Epson, Japan). The accuracy of targeting on radiochromic images was 

investigated in three-dimensionally by the end-to-end analyzer manufactured 

by Accuray. 

Results: The period of the moving phantom was 2.5~5 second. The errors of 

targeting were less than 0.7 mm for each directions. The mean square error 

was less than 1 mm, which was independent of period of the moving phantom 

Conclusions: It was found that the respiratory tracking system of fourth generation 

CyberKnife has the error within 1 mm. Therefore, the error of the 

tracking system could be reduced by regulating the patient’s respiration. 

1229 poster 

STUDY ON THE IMPACT OF RESPIRATORY MOVEMENT ON DOSE 

DISTRIBUTION USING AN IN-HOUSE ORGAN MOTION PHANTOM 

P. Babu Rao 1 , A. Mahata 1 

1 CHRISTIAN MEDICAL COLLEGE, Department of Radiation Oncology, 

Vellore, India 

Purpose: Respiratory and cardiac motions cause the largest displacements 

in intrathoracic tumors. The magnitude of displacement varies significantly 

with patient, position and size of the tumor and respiratory pattern of the 

patient. Lung motion during treatment results in an increase in the treated 

volume and the delivered dose distribution does not match the planned dose 

distribution. The purpose of this study is to develop an organ motion phantom 

that could simulate the tumor motion in the lung and investigate the resultant 

dose distribution due to the longitudinal motion of the lung with GafChromic 

films and Gel dosimetry 

Materials: A thorax shaped phantom made of acrylic filled with water was 

made. The phantom has two cylindrical inserts that represent the lung and 

one of them is attached to a movement system that can simulate the longitudinal 

respiratory motion of the lung with varying frequencies. The lung 

cylinder has provisions to place a GafChromic film or could be filled with Fe 

gel used for gel dosimetry. The respiratory motion in the phantom could be altered 

to simulate the respiratory movement of the patient. A GafChromic film 

was placed in the lung insert and was first exposed to a 5cm 2 field without 

any respiratory movement and then with varying frequencies of the respiratory 

motion. Similar experiment was performed with Fe Gel filled in the lung 

insert. 

Results: The dose distribution obtained without movement of the film (no respiratory 

movement) was compared with the dose distributions obtained with 

varying frequencies of respiratory movement. The dose distribution with the 

phantom (film) movement differed significantly from the dose distribution without 

phantom (film) movement. The area of the high dose region was reduced 

suggesting that the prescribed dose was delivered only on the area that was 

always within the radiation beam during the respiratory motion. However, the 

low dose region was elongated as larger volume was involved in the radiation 

beam due to the respiratory movement. The variation in the dose distribution 

due to different frequencies of the respiratory motion was insignificant. 

Conclusions: A phantom to study the impact of respiratory motion on lung 

treatments has been developed and the dose distribution obtained with respiratory 

movement differed significantly suggesting the need for gated treatments. 

1230 poster 

SUITABILITY OF MOSFETS FOR QUALITY ASSURANCE OF RU-106 

OPHTHALMIC PLAQUES 

E. Drud 1 , X. Sheng 1 , F. Cremers 1 

1 UNIVERSITY MEDICAL CENTER HAMBURG-EPPENDORF, Department of 

Radiotherapy and radio-oncology, Hamburg, Germany 

Purpose: Opthalmic plaques are used to treat tumors of the eye (e.g. 

retinoblastoma). Ru-106 is a widely used beta-particle emitter. Dosimetry 

of beta radiation is difficult due to the large gradients of the depth-dose curve. 

Dosimeters for beta sources therefore must have a very small volume. Otherwise 

the secondary-particle equilibrium to fulfill Bragg-Gray conditions cannot 

be established and dosimetry is impossible. The dose rate values provided by 

the manufacturer of the ophthalmic plaques have an uncertainty of +/-20%. 

Up to now only thermoluminescence detectors (TLDs) are used for quality assurance 

(QA) of Ru-106 ophthalmic plaques at our department. TLDs have 

several disadvantages such as teadious handling. The whole QA process 

takes several hours. As ophthalmic plaques are sometimes reused in short 

intervals QA can only be performed between two applications. MOSFET 

dosimeters have a very small active volume which makes them well suited 

for measurements in fields with steep dose gradients. They also allow instant 

readout in Gray after they have once been calibrated. In this study the 

suitability of MOSFET dosimeters for quality assurance of Ru-106 ophthalmic 

plaques was investigated. 

Materials: For QA of the Ru-106 ophthalmic plaques a TLD rod is put into 

one of the spherical plaques and left there for a certain time. No phantom material 

is used so the contribution of backscattering is missing. The TLDs have 

to pass a heating process prior to irradiation and are being reheated for dose 

evaluation. Besides they have to be calibrated before each measurement.The 

MOSFET dosimeters (Thomson and Nielson, Ottawa, Canada) have an active 

area of 0.04 mm. There are no published data on the thickness of the 

active area. As the effect of radiation on MOS devices is an interface effect, 

the thickness is in the order of few atom layers. A reader which is connected 

to a PC allows instant readout. The MOSFET was placed on a ball of paraffin. 

Then the Ru-106 plaque was put on top. 

Results: Dose values measured with MOSFETs are approx. 12% higher 

than those measured with TLDs. A reason for the higher response is the additional 

contribution of backscattering, as the MOSFET measurements were 

performed in a primitive phantom. 

Conclusions: In conclusion MOSFETs could be a practical alternative to

measurements with TLDs. 

1231 poster 


SUPERFICIAL TLD DOSE MEASUREMENTS FOR HEAD AND NECK 

CANCERS TREATED BY TOMOTHERAPY 

I. Pasquie 1 , E. Poupon 1 , P. Caradec 1 , C. Munos 1 , E. Bardet 2 , A. Lisbona 

1 

1 CRLCC NANTES ATLANTIQUE, Physics, Nantes, France 

2 CRLCC NANTES ATLANTIQUE, Radiation Oncology , Nantes, France 

Purpose: Helical tomotherapy is a novel radiotherapy treatment modality 

that delivers intensity modulated radiation in a rotational way. The use of 

51 6MV fan beams every 7 degrees enables to conform dose distributions to 

target volumes. Some works points out increased superficial dose resulting 

from obliquity effects when multiple tangential beams are applied to head and 

neck treatments. The purpose of this study is to compare skin doses measured 

with thermoluminescent dosimeters (TLDs), to doses calculated with 

tomotherapy Treatment Planning System (TPS). 

Materials: Measurements are performed at the Renuducheau CRLCC 

Nantes Atlantiques, France, on patients treated with tomotherapy for head 

and neck cancers. Three thermoluminescent dosimeters are placed underneath 

a five points immobilization mask on the skin of patients, one under the 

chin, one on the right up-collarbone and the last one on the left up-collarbone. 

Dose data are collected on several head and neck patients throughout the 

course of their treatment on a tomotherapy unit. 

Results: A total of 207 measurements are taken on 5 different head and neck 

patients. Dose measured with TLDs on the first patients are compared with 

calculated doses, a maximum standard deviation of 5% is obtained. Dose 

standard deviation on each dosimeter position is about 11% with a maximum 

of 17%. This significant deviation may come from uncertainties due to high 

gradient dose regions close to TLDs. 

Conclusions: To complete this study an anthropomorphic phantom is used to 

improve the reproducibility of the TLDs positioning. Furthermore skin sparing 

structures with dose constraints are used in dosimetric treatment plans in 

order to decrease superficial doses and the efficiency of those structures is 

evaluated. 

1232 poster 

THE EFFECT OF CLOTHING ON THE SKIN DOSE DURING 6 MEV 

TOTAL SKIN ELECTRON (TSE) IRRADIATION USING GAFCHROMIC 

EBT FILM 

R. Ramer 1 , T. Tynan 1 , T. Eng 2 , C. Esquivel 1 , N. Papanikolaou 1 


2 UTHSCSA, Radiation Onocology, San Antonio, USA 

Purpose: The purpose of this study was to determine what effect allowing 

the patient to wear various articles of clothing might have on the dose delivered 

to the patient. Total skin electron (TSE) radiotherapy is a standard form 

of treatment of mycosis fungoides, a form of cutaneous T-cell lymphoma.1 

TSE delivers a dose of radiation to the total body using electrons to treat 

the shallow affected region while sparing deeper tissues. During these treatments 

patients are typically required to be unclothed. In order to maintain 

the patient’s dignity and increase their comfort in often-chilly treatment vaults, 

it would be desirable to allow them to wear clothing. Gafchromic EBT films 

allow measurements at only slightly below the clinically relevant skin dose 

depth of 70 µm, while providing a 2D dose profile. 

Materials: A Rando (Phantom Lab, Salem, NY) phantom was placed in a 

standard upright treatment position. The midline of the patient was 150 cm 

from the isocenter. A Plexiglas degrader was placed 10 cm in front of phantom. 

Squares, 2cm x 2cm, and strips, 2 cm x 25 cm, of Gafchromic EBT film 

(ISP Corp, New Jersey) were placed at strategic locations on the phantom. 

The phantom was dressed in various outfits and measurements were taken 

for each. These outfits included (1) fully dressed: t-shirt, sweatpants, underwear 

and bra, (2) underwear and bra, (3) hospital gown, and (4) no clothing. 

A standard TSE treatment,1 consists of several pairs of angled fields (usually 

12 or 6 fields) providing a prescription dose of 200 cGy to the umbilicus for 

each fraction. One pair of fields, with a planned dose of 66 cGy, was delivered 

from a CLINAC 23EX (Varian Medical Systems, California) using the 6 MeV 

HDTSE electron mode, for each outfit. Measurements were compared with 

concurrent TLD measurements. The Gafchromic EBT film was allowed to sit 

for 24 hrs before reading to allow for maximum dose grow-in.2 

Results: It was found that all outfits caused a noticeable change in measured 

dose. The doses measured by Gafchromic EBT film differed from the 

expected dose and the TLD measured dose, although the expected and TLD 

doses were in agreement. Measured doses for each outfit are summarized in 

Table 1. 

Conclusions: The data obtained with the Gafchromic EBT film did not match 

the expected dose, or the TLD measurements. No patterns were found in 

these differences. In investigating possible reasons for the discrepancy, the 

2D dose distribution and was found to have insignificant variation. 

1233 poster 

S 393 

THE FEASIBILITY OF A HELICAL DOSIMETRY SYSTEM FOR 

HYBRID PLAN QUALITY ASSURANCE OF IMRT 

T. Depuydt 1 , I. Gomola 2 , A. Swinnen 1 , F. Van den Heuvel 1 

1 

UNIVERSITY HOSPITALS LEUVEN, GASTHUISBERG, Radiotherapy, Leuven, 

Belgium 

2 

IBA DOSIMETRY, Schwarzenbruck, Germany 

Purpose: To evaluate suitability of a Helical Dosimetry R○system (IBA), consisting 

of a 2D ion chamber array (IC) detector and a dedicated plastic phantom 

for hybrid plan QA of static gantry IMRT and rotational dose delivery 

techniques. 

Materials: For verification of IMRT and rotational dose delivery techniques 

the 2D IC array was placed horizontally in the phantom. A dose calculation of 

the hybrid treatment plan was performed on a CT scan of the phantom with 

unchanged treatment plan parameters. Gamma analysis (?dose=3% and 

?distance=3mm) was used for comparison between measured and calculated 

dose distributions in the active plane of the detector. The dose comparison 

was done both for the total hybrid plan and for the separate treatment fields. 

The impact of couch top attenuation and angular dependence of the 2D IC 

array detector on the clinical application of this QA solution was investigated. 

In addition, was evaluated the influence of air cavities in the 2D IC array on the 

performance of both algorithms available in the Eclipse (TPS from Varian), for 

the Pencil Beam Convolution (PBC) and the Analytical Anisotropic Algorithm 

(AAA). 

Results: For treatment fields delivered to the backside of the detector and 

passing through the couch, discrepancies between measurement and calculation 

of up to 7%, relative to the maximum field dose, were observed. The 

couch top attenuation contribution was approximately 4%. The angular dependence 

of the detector was below 3%. For fields with angles nearly parallel 

to the detector plane, the AAA calculation showed better agreement with the 

measurement than the PBC. For the gamma evaluation of the total dose of the 

hybrid plan the criterion resulted in agreement scores of more than 97%. For 

a field by field evaluation the combined impact of couch top attenuation and 

angular dependence of the detector (Figure 1(c),(d)) and the reduced dose 

calculation accuracy in low density media in case of PBC (Figure 1(a),(b)), 

introduced errors exceeding the 3%,3mm constraints. The data presented 

here are from static gantry IMRT, however, the results are also applicable to 

rotational techniques.


Conclusions: The Helical Dosimetry R○system is offering fast an accurate 

patient specific dosimetry QA of IMRT for hybrid plans as well as separate 

treatment fields on the fraction level. It is advised to account for couch top 

attenuation in dose calculation and to apply advanced dose calculation algorithms 

for accurate prediction of the 2D array detectors response. 

1234 poster 

THE STATISTICAL ANALYSIS OF PATIENT SPECIFIC DOSIMETRY 

QUALITY ASSURANCE (DQA) OF IMRT PLANS 

J. B. Chung 1 , J. S. Kim 1 , I. A. Kim 1 , J. M. Park 2 , Y. G. Park 3 , H. J. Kim 

2 , H. G. Wu 4 , I. H. Kim 4 , E. K. Chie 4 , T. S. Suh 5 , S. J. Ye 4 

1 

SEOUL NATIONAL UNIVERSITY BUNDANG HOSPITAL, Radiation Oncology, 

Seongnam, Korea Republic of 

2 

SEOUL NATIONAL UNIVERSITY GRADUATE SCHOOL, Radiation Applying 

Life Science, Seoul, Korea Republic of 

3 

SEOUL NATIONAL UNIVERSITY COLLEGE OF MEDICINE, Institute of 

Radiation Medicine, Seoul , Korea Republic of 

4 



5 

THE CATHOLIC UNIVERSITY OF KOREA, Department of Biomedical 

Engineering, Seoul, Korea Republic of 

Purpose: By analyzing measured results of patient specific DQA (dosimetry 

quality assurance) of IMRT plans, we identified several factors that affected 

the discrepancy between calculated and measured doses. 

Materials: From July 2006 to February 2008, patient specific DQA for 153 

IMRT plans of head and neck (H&N) cancer, prostate cancer, and brain tumor 

was performed by using a home-made cylindrical phantom. A verification 

point was selected in the regions of uniform and high dose. A diode array 

was used to compare individual fluence maps in a γ-index method. 

Results: The average difference between calculated and measured doses 

was -1.54±1.35% for H&N cancer, 0.13±1.05% for prostate cancer, and - 

0.70±1.34% for brain tumor. The maximum difference was -3.4% for H&N 

cancer, -3.4% for brain tumor, and 2.5% for prostate cancer. Planed and 

measured fluence maps were in agreement of 95.8±7.4% with the γ-index 

criteria of ±3 mm and ±3%. The number of PTVs, the number of split fields, 

and the degree of modulation showed strong correlations with the discrepancy 

between them. Most IMRT plans (96%) agreed with measured doses 

within the tolerance level of ±3% on patient specific DQA. However, we found 

systematic underdosage of highly modulated H&N plans while dose differences 

of other cancer patients followed the Gaussian distribution. 

Conclusions: We recommend that highly modulated plans over the tolerance 

level should be avoided even though they can be generated by RTP. We 

suggest that dosimetric corrections for IMRT plans over the tolerance level 

could be achievable only with an established IMRT QA protocol. 

1235 poster 

THERMOLUMINESCENT DOSIMETRY IN THE QUALITY ASSUR- 

ANCE OF LYMPHOMA CLINICAL TRIALS 

P. Diez 1 , P. Hoskin 2 

1 

MOUNT VERNON HOSPITAL, Clinical Physics, Northwood Middlesex, 


2 

MOUNT VERNON HOSPITAL, Northwood Middlesex, United Kingdom 

Purpose: In vivo dosimetry using thermoluminescent dosimeters (TLDs) for 

dose verification is widely accepted in clinical trial quality assurance (QA). QA 

programmes for two UK phase III randomised lymphoma clinical trials have 

included TLD dosimetry. The first a trial for advanced Hodgkin’s Disease 

comparing chemoradiation in the Stanford V schedule with ABVD, the other 

a trial of low dose radiotherapy (RT) for follicular lymphoma (FoRT). 

Materials: A cohort of patients from both the Stanford V (2002-2006) & FoRT 

(2006-2008) trials was monitored using postal TLDs despatched from & returned 

for analysis to the QA centre at Mount Vernon Hospital. The TLDs 

were placed at the centre of each field for the full duration of a single fraction 

treatment exposure. For parallel-opposed fields, the entrance & exit doses 

were measured & compared to the calculated mid-plane dose; for other multifield 

treatments surface doses were compared to the calculated dose from the 

teatment plan, supplied to the QA centre. 

Results: A total of 458 patients have received RT in the two trials, (Stanford 

V/ABVD 80.8%, FoRT 19.2%) of which 99 (21.6%) had TLD measurements 

(Stanford V/ABVD 74.7%, FoRT 25.3%); these were submitted from 

18 (40.9%) of the 44 centres involved. The mean & SD variation of measured 

dose from the expected dose was 3.12 ± 2.83%. Nine patients had measurements 

of >10% different to the expected dose, of which 3 were resolved 

with repeat measurements. QA identified 2 cases where the prescribed dose 

was outside trial protocol specifications & 3 where the treated volume was 

larger than outlined in the protocol. 

Conclusions: This TLD QA process identified 9 (9.1%) patients in whom a 

significant variation in dose from the protocol was measured. In 3 there may 

have been a measurement error which was resolved by repeat measurement 

leaving a total of 6 (6.1%) confirmed protocol deviations in this sample. Four 

of these were in neck fields where large gradient changes occurred from the 

oblique incidence. The other 2 were in the mediastinum where fields were 

very large, immobilisation poor & there are major tissue homogeneity issues 

encountered. These were eventually resolved by diode readings supplied by 

the treating centre or checks carried on water-equivalent blocks. In summary 

TLDs have proved a practical & valuable QA tool identifying a 6% deviation 

from protocol & highlighting the need for each patient undergoing RT to have 

in vivo dosimetry. Modern systems using diodes may, however, displace this 

traditional means of postal QA. An optimal QA programme will also include 

full dosimetry audits & collection & analysis of patient plans. 

1236 poster 

TLD AUDIT IN RADIOTHERAPY CENTERS IN BULGARIA - 2006/2007 

K. Sergieva 1 

1 QUEEN GIOVANNA UNIVERSITY HOSPITAL, Oncotherapy , Sofia, Bulgaria 

Purpose: The purpose of this work is: To continue the external TLD audit in 

all Bulgarian radiotherapy centers and to expand it in non reference conditions 

on axis and off axis. 

Materials: High energy photon Co-60 beams IAEA water phantom 

Manual TLD reader (Fimel LTM) IAEA capsules, LiF powder The dose 

absorbed to water DTLD [Gy] is: DTLD=MxNxflinxffadxfen, where M- 

TLD readings; Ncalibration coefficient of TLD system; flinnon-linearity 

dose response correction factor; ffadfading correction factor; fenenergy response 

correction factor. The deviations are defined by: ∆=(DSTATED 

DTLD)/DTLD*100%, where DSTATED User stated dose reported by the participants; 

DTLD SSDL measured dose. Deviations are based on values ∆. 

" ∆ ≤5% - acceptable level " ∆≥5% - major deviation and in site visit audits 

in details necessary " ∆>10% - emergency level and prompt actions is 

necessary The TLD audits are organized in the 3 steps in 2006 and 2007. 

Results: Step1: Beam output in reference conditions. The reference 

beam output is checked for S=10x10 cm at depth d=5cm for 11 beams from 

all radiotherapy centers in 2006. The distribution of ratio D(TLD)/D(stated) 

is: N=11; mean=0.999; rel. Stdev=2.1% Step2: Dose in reference and 

non-reference conditions on-axis. /graph 1/ The audit is included open 

and wedge fields. The sizes of the fields are: 10x10 cm, 7x7 cm, 7x20 cm, 

20x20 cm, 7Wx20 cm and 10Wx10 cm. The next dosimetric parameters 

are checked for 6 beams from 5 centers in 2006. 2.1 The reference beam 

output 2.2 Beam output variation 2.3 Wedge transmission factor The 

distribution of the ratio D(TLD)/D(stated) for all points is: N=36; mean=1.004; 

rel. Stdev = 2.0% graph. 1 Step3. Dose in non-reference conditions 

off-axis.The reference beam output, open and wedged field profiles, ratios 

D(20X20)/D(10X10) and Dwedged/Dopen are estimated using TLD. The TLD 

measurements on-axis and two positions off-axis ±5 cm, with and without 

wedges at 10 cm depth in water at SSD =75 cm are done for 4 beams from 

3 centers in 2007. The distribution of the ratio D(TLD)/D(stated) for all points 

is: N=44; mean=1.023; rel. Stdev = 1.7%


Conclusions: All checked beams comply with the acceptance level in all 

steps. The TLD audits in Non-reference conditions On axis and Off axis 

is successfully expanded and will applied in the next TLD audits. Acknowledgements 

This investigation has been supported by the IAEA through RC 

N11915Ro. 

1237 poster 

TRUE 3D-DOSIMETRIC VERIFICATION OF STEREOTACTIC RA- 

DIOTHERAPY (SRT), IMRT AND HELICAL TOMOTHERAPY ? A 

COMPARISON 

M. Todorovic 1 , M. Fischer 1 , D. Albers 1 , F. Cremers 1 

1 UNIVERSITY MEDICAL CENTER HAMBURG-EPPENDORF, Department of 

Radiotherapy and Radio-Oncology, Hamburg, Germany 

Purpose: The capability of commercial BANG gel (MGS Research, Inc., 

Madison, CT, USA) for external beam dose verification like SRT, IMRT and tomotherapy 

(Hi-Art) is investigated in this paper. Compared to films, BANG gel 

provides true 3D dose distributions in a tissue-equivalent medium. New techniques 

like tomotherapy require a high accuracy of dose calculation and delivery. 

To verify the accuracy of delivery we compared the results of the BANG 

gel measurements read out with a commercial OCTOPUS laser CT scanner 

(MGS Research, USA) to those obtained using the established GafChromic 

EBT films (two-dimensional). 

Materials: SRT, IMRT and tomotherapy treatment planning for a typical head 

and neck case was performed. The verification measurements were done using 

a µMLC manufactured by 3DLine in combination with a Siemens Primus 

(SRT and IMRT) and a helical tomotherapy treatment unit. The BANG gel 

was irradiated using a special adapter in our multi-purpose phantom (Easy- 

Cube, Euromechanics) also used for the film measurements. The read out 

of the BANG gel was done using the OCTOPUS scanner. The Scanner is 

designed for imaging 3D distributions of optical attenuation coefficient distributions 

in BANG gel for the use in 3D dose distribution measurements. The 

GafChromic EBT films were scanned after irradiation using a flat-bed scanner 

(Epson) and compared with the data provided by the BANG gel using selfwritten 

MatLab routines. Also voxel-by-voxel comparison of measured (BANG 

gel) and calculated dose distribution was done. 

Results: The use of polymer gel for verification of SRT, IMRT and tomotherapy 

was validated. The results for all three treatment types will be presented. 

As the GafChromic EBT is the established method for SRT and IMRT verification 

in our department, we first compared the 2D dose distributions derived 

from the GafChromic EBT with the BANG gel measurements. In the second 

step, we compared the calculated dose distributions with the true 3D data 

derived from the BANG gel. The gel measured dose distributions will be presented 

in comparison with the calculated plans. 

Conclusions: We found BANG gel dosimetry to be suitable for SRT, IMRT 

and tomotherapy. The results obtained with BANG gel dosimetry are comparable 

to the measurements from GafChromic films. The combination of 

Bang Gel and the OCTOPUS laser-based CT scanner is a very promising 

approach to the verification of true 3D dose distributions without the use of 

an MRI scanner. 

1238 poster 

USE OF GAFCHROMIC R○ EBT FILMS IN ELECTRON BEAMS RA- 

DIOTHERAPY. APPLICATION TO CLINICAL TREATMENT PLANNING 

SYSTEMS QUALITY ASSURANCE. 

J. El Barouky 1 , N. Fournier-Bidoz 1 , L. Simon 1 , S. Zefkili 1 , J. C. Rosenwald 

1 

1 INSTITUT CURIE, Medical Physics Departement, Paris, France 

S 395 

Purpose: Electrons radiotherapy is used in a wide range of cancer localizations. 

However, algorithms used for dose calculations in Treatment Planning 

Systems (TPS) are still in progress. In addition, measurements are more 

difficult to achieve in electron beams compared to photon beams. Usual dosimetric 

detectors do not fit to all geometric situations. 

Materials: New radiochromic films, GAFCHROMIC R○EBT, have been recently 

released in the market. Because they are not sensitive to visible light, 

they are easy to manipulate and can be shaped to any phantom. Their high 

resolution is adapted to the QA tests performed in a radiotherapy department. 

We first studied the feasibility of using GAFCHROMIC R○EBT films with electron 

beams: first level tests have been performed to compare the film measured 

data to that given by an ionization chamber in a water phantom (PDD, 

profiles and absolute dose). Then we used the EBT films for different quality 

assurance tests in electron beams as recommended by the IAEA TRS 

N ◦ 430: oblique incidence, complex surface shapes and heterogeneities. In 

order to evaluate the validity of electron beams dose distributions calculated 

by the Treatment Planning System Eclipse (Varian R○) we compared them to 

the measured data with the EBT films. 

Results: The PDD curves showed good agreement with the reference curves 

of the ionization chamber after the build up region. In the build up region the 

results were poorer but acceptable. Good agreement was observed with the 

profile curves. The EBT films dose distributions showed good agreement with 

the TPS Eclipse dose distributions for different QA tests. The figure below 

shows an example of the results we obtained using these films. 

Conclusions: This study shows the feasibility of using 

GAFCHROMIC R○EBT films with clinical electron beams. The QA 

tests were successfully performed using these films. 

1239 poster 

VALIDATION OF DELTA4 FOR CLINICAL USE 

E. Persson 1 , U. Granlund 1 

1 ÖREBRO UNIVERSITY HOSPITAL, Department of Medical Physics, Örebro, 

Sweden 

Purpose: The aim of this work was to validate the Delta4-system (ScandiDos 

AB, Uppsala, Sweden) for clinical use in the IMRT QA process. 

Materials: The Delta4-system consists of two perpendicular planes containing 

1069 diodes in a cylindrical PMMA-phantom, and is designed to check a 

complete treatment plan in one single measurement. Simple field arrangement 

with 6 MV photons was used to evaluate the system. Dose linearity was 

studied using one single field irradiated with varying number of monitor units, 

from 2 MU to 500 MU. Short term reproducibility was studied with repeated 

irradiation of a single field. For stability evaluation a 4-field box plan was measured 

a number of times during a long time period. Angular-, pulse rate- and 

dose rate dependence was also evaluated. 

Results: The system showed good dose linearity. For short term reproducibility 

the maximum standard deviation was 0.65% for 10 subsequent irradiations, 

inside the field the maximum standard deviation was 0.1%. Maximum 

deviation for the stability test was 0.7%. A minor pulse rate dependence 

was found. The system has a certain angular dependence, especially for angles 

nearly parallel to any of the detector planes. To avoid this problem for 

fields within ±5 from the detector planes it is possible to use the phantom in 

reversed position. 

Conclusions: The Delta4-system is suitable for clinical use, but field angles 

parallel to any of the detector planes should be avoided. 

1240 poster 

VERIFICATION OF DELIVERED PATIENT DOSE IN EXTERNAL 

RADIOTHERAPY IN SWEDEN 

J. Eriksson 1 , M. Blomquist 1 , J. Olofsson 1 , M. Karlsson 2 

1 UMEÅ UNIVERSITY HOSPITAL, Radiation Physics, Umeå, Sweden 

2 UMEÅ UNIVERSITY, Dep of Radiation sciences, Umeå, Sweden

S 396 PHYSICS AND TECHNOLOGY : BASIC DOSIMETRY AND DETECTORS 

Purpose: The aim of this work was to make a survey regarding the use of in 

vivo dosimetry in external radiotherapy in Sweden. 

Materials: A questionnaire was distributed to 17 radiotherapy departments 

in Sweden. The questions concerned the performance of in vivo dosimetry 

in clinical routine, i.e. procedures, frequency, action level, correction factors, 

error ratio, and actual errors leading to change of patient parameters. Questions 

concerning the future performance of in vivo dosimetry and whether it 

should continue to be mandatory were also asked. 

Results: All 17 Radiotherapy departments answered the questionnaire. All of 

them are performing in vivo dosimetry with diodes, some also complements 

with TLD for organs at risk, etc. The action levels used at the radiotherapy departments 

vary between ±3% to ±10%, with ±5% being the most common 

value. The use of correction factors differs from no factors at all to correcting 

for SSD, field size, beam incident angle, wedges and attenuation in table 

top. The ratio of second measurement, i.e. measurement over tolerance 

level, varies from a few percent up to 20%. To solve the problem with in vivo 

dosimetry for e.g. IMRT and SRT a few radiotherapy departments state that 

they are considering EPID in vivo dosimetry. The Swedish radiotherapy departments 

are divided about keeping the, in Sweden, mandatory demand for 

in vivo dosimetry on each patient. 

Conclusions: For conventional treatment techniques in vivo dosimetry is a 

good method to verify the delivered patient dose. However, the questionnaire 

showed that few errors were actually found and performing in vivo dosimetry 

for all patients takes a lot of time. A more effective approach may be 

to perform in vivo dosimetry only for treatments that has an increased risk 

of errors and for new treatment techniques that are still not fully established 

in the clinic. To solve the problem with in vivo dosimetry for complex treatments 

techniques alternatives to diode and TLD must be considered. EPIDdosimetry 

and transmission ion chambers seem to be a feasible solution for 

IMRT in vivo dosimetry 

Physics and technology : Basic 

dosimetry and detectors 

1241 poster 

A DOSIMETRY INTERCOMPARISON PHANTOM FOR INTRAOPERA- 

TIVE RADIOTHERAPY 

K. Armoogum 1 

1 THE PRINCESS ROYAL HOSPITAL, Radiation Physics, Hull, United Kingdom 

Purpose: In any clinical trial where ’identical’ devices are used to deliver the 

same prescribed dose to the same prescription depth, a means of quantifying 

the uniformity of dose delivery among participating centers is essential. 

Dosimetric accuracy is a vital requirement for the transfer of clinical experience 

among centers. The Zeiss Intrabeam TM low kV x-ray source (up to 50 

kV) is used to treat breast tumours as part of an international clinical trial. It 

was proposed to design a simple, robust phantom to be used for a mailed 

intercomparison of Intrabeam TM x-ray sources used in the centers involved in 

the TARGIT breast cancer trial. 

Materials: In this work, we designed, fabricated and investigated a cylindrical 

PMMA dosimetry intercomparison Phantom for intraOperative RadioTherapy 

(iPORT). The iPORT has two advantages over a water phantom. Firstly, the 

iPORT is more convenient for routine use than a water phantom. Secondly, 

the sensitive Beryllium-coated probe of the Zeiss Intrabeam TM does not need 

to be immersed in water for long periods, therefore minimizing degradation 

of the Beryllium. The iPORT phantom was designed under the constraints 

that it should be easy to manufacture, be made of readily available material, 

be simple to use, provide a fixed geometry and be robust enough to be 

mailed. Several phantom designs were appraised before selecting a simple 

cylindrical shape. The iPORT fits over an interlock, which enables the XRS to 

function without being mounted in the gantry. We manufactured an interlock 

out of stainless steel to perform this function however, other materials such 

as aluminum could possibly be used. The shaft of this interlock is 60.3 mm 

long but it is proposed to considerably shorten this to reduce its weight and 

make it more suitable for mailing. 

Results: The performance characteristics of the x-ray sources used in this 

intercomparison have previously been investigated, and they have proven to 

be uniform and stable over time. Any variation in absorbed dose measured 

at 10 mm from the probe tip of each source is therefore likely to arise from 

uncertainties in the measurement technique. We found a variation of ± 3.9% 

in absorbed dose for the four XRS investigated. The overall uncertainty was 

calculated to be 4.73% with the largest contribution from setup errors (2.5%). 

Conclusions: We propose that the iPORT phantom used in conjunction with 

an interlock and Gafchromic R○XR Type R film is a viable dosimetry intercomparison 

system for Intrabeam TM x-ray sources. 

1242 poster 

CHARACTERISATION OF MCP-600D AND MCP-700D THERMO- 

LUMINESCENCE DETECTORS FOR DOSIMETRY OF PHOTONEU- 

TRONS 

E. Brunckhorst 1 , X. Sheng 1 , J. Becker 1 , F. Cremers 1 

1 UNIVERSITY MEDICAL CENTER HAMBURG-EPPENDORF, Department for 

Radiotherapy and Radio-Oncology, Hamburg, Germany 

Purpose: The thermoluminescence material LiF:Mg,Cu,P is a very sensitive 

detector material, that is the most used passive detector material for radiation 

protection purposes. This study presents the characteristics of two special 

high-sensitive types of these detectors named MCP-600D and MCP-700D 

from TLD Poland. As the first type is 6 Li and second one 7 Li enriched, the 

first has a substantial higher sensitivity to neutrons, however they have similar 

photon sensitivity. Both are supposed to be used as paired detectors in the 

determination of photoneutron dose in high-energy photon fields. 

Materials: The used TL detectors have a size of 1 mm x 1 mm x 6 mm 

(square rod). The TLD reader 550 from Harshaw has been used for read 

out. All 150 TLDs of each type that were used in this study have never been 

used before and passed an initialization procedure of several consecutive irradiation 

and annealing cycles first. The optimal time-temperature profiles for 

reading and preheating have been obtained thereafter. Individual response, 

batch homogeneity and reproducibility over several irradiation cycles were 

obtained. The linearity of the detector response was investigated in a photon 

dose range up to 6.5 Gy. The energy dependence was studied for 4, 6 and 

15 MV photons. To check the response to photoneutrons, irradiations in a 

RW3 phantom were performed with tungsten plates on top of the phantom to 

increase the number of neutrons at the point of measurement. 

Results: The following time-temperature characteristics have been obtained 

for the reading procedure: preheating for 5s at 150 ◦ C, heating rate 6 ◦ C/s 

and an annealing temperature of 240 ◦ C. An external preheating for 10 minutes 

at 100 ◦ C is performed after irradiation and an external annealing for 10 

minutes at 240 ◦ C after read out. The batch homogeneity is within 7% for 

MCP-700D and within 11% for MCP-600D. The reproducibility is 4% and 5% 

resp. For both TLD types the detector response is linear up to 6.5 Gy. Energy 

dependence for the MCP-700D is within 2%, for MCP-600D it is within 2% 

for 4 and 6 MV. A higher response of 10% was determined for 15 MV for the 

MCP-600D. The tungsten experiment showed that the MCP-600D detect an 

additional charge in comparison to the MCP-700D. 

Conclusions: The investigated TL material has been characterised and prepared 

for further investigations. The TLDs are suitable for photoneutron detection, 

however long beam-on times and a large number of TLDs are necessary 

for reliable results. 

1243 poster 

CHARACTERIZATION AND EVALUATION OF A DIODE ARRAY 

DETECTOR SYSTEM FOR DYNAMIC AND CONVENTIONAL RADIO- 

THERAPY 

W. Ottosson 1 , F. Nordström 2 , S. Ceberg 2 , S. Bäck 2 

1 

COPENHAGEN UNIVERSITY HOSPITAL, HERLEV, Department of Oncology, 

R, Herlev, Denmark 

2 

MALMÖ UNIVERSITY HOSPITAL, Department of Medical Radiation Physics, 

Malmö, Sweden 

Purpose: To reach the expected treatment goal with radiotherapy and to 

avoid errors in the absorbed dose delivered to the patients all the steps in the 

treatment chain have to be thoroughly controlled with reliable methods and 

detectors. The aim of this study was to develop and evaluate a method for 

characterization and evaluation of the basic dosimetric parameters of a diode 

detector system, LDA-99 (IBA Dosimetry). The feasibility of using the LDA-99

as a reference detector for dynamic radiotherapy technique applications, i.e. 

IMRT and BART (Breathing Adapted Radiotherapy) was also investigated. 

Materials: Both water and air measurements were undertaken for 6 and 18 

MV photons. The dosimetric properties investigated were: linearity of detector 

response, dose rate, pulse rate, energy and directional dependence. 

Output factors were compared with ion chamber measurements. Depth dose 

curves measured in water for different field sizes and energies were compared 

with reference data. An IMRT verification field for a head and neck 

treatment was measured using the LDA-99 by repeated irradiations. Absorbed 

dose from two segments, 7MU each, was missing in the TPS (Master- 

Plan, Nucletron) calculated dose distribution due to a software malfunction. 

For the evaluation of the 2D IMRT measurements performed with the LDA-99 

a MATLAB software was developed and a gamma evaluation routine was implemented. 

The measured 2D dose distribution was compared with the TPS 

calculated data. For comparison the same IMRT field was measured using a 

2D ion chamber array (Seven29, PTW) and the gamma evaluation was executed 

using Verisoft (PTW). Further, the LDA-99 was mounted on an in-house 

developed breathing robot when investigating the feasibility of using it for verification 

of BART. The correlation between the gated and the static profiles for 

a 5x5 cm2 field using an 11 mm breathing motion were investigated. Also, a 

nongated profile was obtained during motion. 

Results: The LDA-99 results agreed well with reference data. A directional 

dependence of up to 90% was observed when the gantry was rotated 70 

degrees. The LDA-99 deviations compared to reference data were less than 

1% for field sizes larger than 4x4 cm2 and depths beyond dmax. The gamma 

index for the LDA-99 measurements correlated well with Verisoft’s gamma 

index of the Seven29 measurements. Owing to the higher spatial resolution 

for the LDA-99, more detectors failed the criteria 3%/3mm for the LDA-99 

measurements. The gated and static BART profile measurements correlated 

within 1,1 mm in field size which was owing to the few measurement points in 

the penumbra. 

Conclusions: The LDA-99 is suitable for commissioning of TPS data. It can 

be used as a reference detector for the BART application and for measuring 

individual profiles of IMRT fields. The gantry should be positioned perpendicular 

to the detector surface when executing the measurements to avoid 

uncertainties associated with the direction of the incident photons. 

1244 poster 

CHARACTERIZATION OF A DETECTOR SYSTEM FOR ON-LINE 

VERIFICATION IN IMRT 

C. Peroni 1 , N. Givhechi 1 , L. Berta 1 , B. Baiotto 2 , C. Brusasco 3 , R. Cirio 

1 4 3 1 5 3 

, M. Donetti , A. Giuliacci , S. Iliescu , F. Marchetto , L. Mueller , M. 

Stasi 2 

1 

UNIVERSITA’ DI TORINO, Dipartimento di Fisica Sperimentale, Torino, Italy 

2 

A.S.O. ORDINE MAURIZIANO DI TORINO E IRCC DI CANDIOLO, S.C. Fisica 

Sanitaria, Italy 

3 

IBA S.A., Louvain-la-neuve, Belgium 

4 

FONDAZIONE CNAO, Milano, Italy 

5 

ISTITUTO NAZIONALE DI FISICA NUCLEARE, Torino, Italy 

Purpose: IMRT requires a dedicated procedure to verify the correct delivery 

of the treatment plan of each patient consisting in the comparison before 

treatment of the dose distribution calculated by the TPS with the one measured 

with an independent dosimeter. On-line dosimetry completes this procedure 

by monitoring the delivered dose during the patient treatment. The 

aim of this work is to verify the performances of the Compass TM system designed 

both for patient pre-treatment verification and for on-line dosimetry. 

Materials: The Compass TM system consists of a dedicated control and analysis 

software interfacing two possible detectors mounted at the head of the 

linac with the appropriate holder: a 2D transmission detector (with 1600 pixels 

arranged in a matrix 40x40) or the 2D ionization chamber MatriXX TM . In 

this preliminary study, only a sub-set of the system features were exploited. 

The DICOM file for patient’s CT and plan structures were fed to the software 

that computed the dose distribution in patient geometry (computed dose). 

From the detector’s measurements, the software reconstructed the dose distribution 

(reconstructed dose) and a comparison between an independent 

measurement, TPS, reconstructed dose and computed dose was made. As 

a proof of validation of the system, we used MatriXX TM mounted at the head 

of a Clinac 600/D and a delivered a set of square fields, 8 simple dynamic 

plans (e.g. garden fences, wedge with MLC) and an IMRT plan for prostate 

with 5 beams. The reference dosimeter for this set up was again MatriXX TM 

set on the couch and the gantry angles were at 0 ◦ . 

Results: The comparison was performed using the "gamma method"; with 

3% relative difference, 3 mm DTA and a threshold at 20% of dose maximum. 

The percentages of failing points for square fields were always below 5% in 

every cross comparisons: TPS Vs reference measure, TPS Vs computed 

dose, TPS Vs reconstructed dose, reconstructed dose Vs reference measure 

and computed dose Vs reconstructed dose. For the 8 simple dynamic plans 

the percentages of failing points were below 0.3% in every cross comparison 

except for 6 plans with regard to the comparison of TPS Vs computed, and for 

2 plans with regard to the comparison reconstructed Vs reference measurement. 

For the IMRT plan the percentages of failing points were between 0%, 

for computed dose Vs reconstructed dose, and 2.26%, for TPS Vs computed 

dose. 

PHYSICS AND TECHNOLOGY : BASIC DOSIMETRY AND DETECTORS 

S 397 

Conclusions: Preliminary results show a general agreement between 

Compass TM dose reconstructions and the reference measurements. Further 

studies are in progress with the use of the transmisson detector and with 

GAF-Chromic film in an antropomorphic phantom as reference. 

1245 poster 

DIFFERENCES ON THE NEUTRON FIELD IN A VARIAN 2100CD 

LINAC FACILITY DUE TO IMRT OR NON-IMRT TREATMENTS 

M. J. Garcia-Fuste 1 , A. Sanchez-Reyes 2 , C. Domingo 1 , K. Amgarou 1 , E. 

Morales 1 , J. Castelo 1 

1 UNIVERSITAT AUTÒNOMA DE BARCELONA, Grup de Física de les 

Radiacions, Dept. Física, Cerdanyola, Spain 

2 CLINICA PLATO, Grup de Física de les Radiacions, Dept. Física, Barcelona, 

Spain 

Purpose: The use of IMRT treatments with high energy linear electron accelerators 

(LINACs) for medical cancer treatments is becoming widespread 

on an international scale. The associated Bremsstrahlung X-rays may produce 

neutrons as a result of subsequent photonuclear reactions with the different 

materials constituting the accelerator head. The generated neutron 

field is highly variable and depends strongly on the beam energy, on the accelerator 

shielding, on the flattering filter as well on the movable collimators 

(jaws) design, and on the geometry field used for irradiation. Neutron fields 

generated with IMRT and conventional treatments may show differences that 

increase the neutron dose delivered to patients. An estimate of these different 

photoneutron components is of practical interest in order to quantify the 

differences of radiological risk for the patients. Due to high frequency electromagnetic 

fields, and also to the presence of abundant leaked and scattered 

photons in these installations, measurements of the corresponding neutron 

fields by active dosemeters are extremely difficult. 

Materials: Neutron doses from uniform dynamic multileaf collimation fields 

were measured for 18 MV on a Varian 2100 CD 120 Millenium MLC using the 

UAB Bonner Sphere System (BSS) based on passive gold activation detectors. 

Neutron measurements were carried out under identical conditions for 

2 prostate patients. The measured neutron dose from these patients were 

compared with the corresponding data from uniform fields (3DCRT treatment) 

having similar jaws setting. Dosimetric planning was carried out using 

ECLIPSE Varian and HELIOS IMRT module. 

Results: The following figure shows the neutron spectrum on tha isocenter 

and a off axis placed at 75 cm from isocenter. Neutron dose measured is very 

similar to those obtained by Howell et al (Med.Phys. 2006 Feb;33(2):360-8) 

Conclusions: The data reported herein show an increase in the secondary 

neutron dose for high-energy IMRT in comparison toconventional radiotherapy 

from 18 MV IMRT. This increased secondary neutron dose appears to 

scale directly withbeam-on time as others have suggested.This work was 

supported in part by a grant FIS PI06/0394 

1246 poster 

DOSE DELIVERY ACCURACY AT LOW MONITOR UNITS FOR 

MEGAVOLTAGE BEAMS 

H. Acun 1 , G. Kemikler 1 

1 ISTANBUL UNIVERSITY ONCOLOGY INSTITUTE, Medical Physics, Istanbul, 

Turkey 

Purpose: The aim of IMRT (intensity modulated radiation therapy) is to deliver 

complex three-dimensional (3D) dose distribution. IMRT is usually delivered 

by a multileaf collimator (MLC) to generate non-uniform beam profiles. 

The step-and shoot IMRT is often required a number of multiple small segments 

and small monitor units. The purpose of this study is to investigate


the properties of the delivery accuracy at low monitor units at an ONCOR 

(Siemens) linear accelerator for 6MV and 18MV photon beams. 

Materials: All measurements were obtained using with PTW 0.125 

cm3semiflexible ionization chamber connected with PTW UNIDOS electrometer 

in solid water phantom. The chamber was positioned at the centre of 

10x10 cm2 field and at the depth of 5 cm in the phantom located at 100 cm 

FSD. The delivery accuracy was evaluated for 50 MU/min and 300 MU/min 

for 6 MV, 50 MU/min and 500 MU/min for 18 MV. The relative dose (RD) was 

found as a ratio of dose delivered per MU at the testing to that of the calibration 

conditions. 

Results: It is observed that the RD for different MU settings for 6 and 18 

MV photon remains with deviations less than 10% for 2 MU at setting of 

50 MU/minute. The RD deviates 5% to low dose of 2 MU for 6 MV at 300 

MU/minute setting. For 18 MV, the deviation is 4% at 500 MU/minute setting 

for 2 MU. For the >2MU the relative deviation is less than 2% for both 6 and 

18 MV photon beam. 

Conclusions: There is no significant deviation in therapeutic MU range for 

Oncor linear accelerator. However, the dose delivery accuracy should be 

analyzed before the implementing of IMRT. 

1247 poster 

ENERGY DEPENDENT RESPONSE OF AL2O3 AND ITS POTENTIAL 

APPLICATION IN PERSONAL MONITORING. 

V. Nelson 1 

1 MACARTHUR CANCER THERAPY CENTRE/SYDNEY UNIVERSITY, Medical 

Physics, Campbelltown, Australia 

Purpose: The aim of this study was to measure the energy dependent response 

of Al2O3, LiF:Mg,Ti and LiF:Mg,Cu,P thermoluminescent dosimeters 

and explore the possibility its application in personal monitoring for x-ray energy 

estimation and improve dose estimation. 

Materials: Ten TL chips of each type of above-mentioned materials were irradiated 

to x-ray beams of varying tube potential from 75 kVp to 300 kVp and 

Co60 gamma radiation. Effective energy of kilovoltage beams was calculated 

from the measured half value thickness of each beam. The responses were 

normalized to 1 mGy dose of Co60 radiation. Using Sigma plot software, 

polynomial fits were obtained to the TL response vs. effective energy. The 

ratio of responses of TLD100 & TLD500H and TLD100 & TLD100500 were 

plotted against the effective energy to investigate the sensitivity of these combinations 

to varying x-ray energy. 

Results: The response of TLD100 and TLD500 decreases with increasing 

x-ray energy, with a peak at approximately 30keV. The response of TLD100H 

initially increases with increasing x-ray energy then decrease with minima 

at approximately 100 keV, after which there is a steady rise to unity in the 

megavoltage region. The ratio of TLRs of TLD500 and TLD 100H showed 

higher sensitivity to variation in energy than the ratio of TLD500 and TLD100. 

Conclusions: Thermoluminescent (TL) dosimetry, especially using LiF, is 

widely used for both personal monitoring and patient dose measurement. 

However, the evaluation of dose may be hampered by the energy dependence 

of the TL materials, which provides the highest contribution to the total 

uncertainty in TL dosimetry. For accurate assessment of dose, information 

on the spectrum of radiation and knowledge of TL response at commonly encountered 

photon energies is essential. The method described above can 

be used to estimate the effective energy of radiation a TL monitor has been 

exposed by including TLD500 TL detector with either of the LiF TL detectors, 

commonly employed in personal monitoring. This will improve the dose 

estimation by applying appropriate energy correction to the response of LiF 

based personal monitors, which are known to exhibit energy dependency in 

the kilovoltage region. 

1248 poster 

ENTRANCE AND PERIPHERAL DOSE MEASUREMENTS DURING 

RADIOTHERAPY 

M. Suleiman 1 , K. Theodorou 1 , I. Tsougos 1 , C. Kappas 1 

1 UNIVERSITY OF THESSALY, Medical Physics, Larissa, Greece 

Purpose: In vivo dosimetry of entrance dose was performed using thermoluminescent 

dosimeters (TLD) in order to evaluate the clinical application of 

the build up caps in patient dose measurements and for different treatment 

techniques. In vivo dosimetry was performed to patient treated with breast, 

head and neck, pelvis and abdomen radiotherapy. Peripheral dose (thyroid 

and skin) was measured for patients during breast radiotherapy to evaluate 

the probability of secondary cancer induction. 

Materials: TLD-100 chips were used with different Copper build up caps (for 

6 MV and 15 MV photon beams from two linear accelerators. Entrance doses 

were measured for patients during radiotherapy course for breast, head and 

neck, abdomen and pelvis malignancies. 

Results: The mean dose ratio was 1.011+0.04, 1.017±0.05, 0.996±0.04 

and 1.003±0.04 for breast, head and neck, pelvis and abdomen, respectively 

compared to the dose derived from theoretical estimation (normalized dose 

at Dmax). The perturbation value can reach up to 20% of the Dmax, which 

acts as a limitation for entrance dose measurements. An average thyroid skin 

dose of 3.7% of the prescribed dose was measured per treatment session 

while the mean skin dose breast treatment session is estimated to be 42% of 

Dmax, for both internal and external fields. These results are comparable in 

those of the in vivo of reported in literature. 

Conclusions: This result has shown reasonable agreement between measured 

and expected doses compared with previous studies. Copper build up 

caps are reliable enough and feasible. The perturbation is the main cause 

of limitation for entrance dose measurements. Careful calibration and placement 

of the build up caps and TLD handling are necessary factors influencing 

the results. It is important for a suitable protection of the thyroid gland to be 

provided especially for patients receiving radical radiotherapy when young. 

1249 poster 

EVALUATION OF A 2D ARRAY FOR LINAC QUALITY CONTROL 

V. I. Pimentel Batel 1 , A. R. Figueira 1 , M. Trindade 2 , A. L. Carvalho 1 

1 HOSPITAL DE S. JOAO, Radioterapia, Porto, Portugal 

2 CENTRO HOSPITALAR TRÁS-OS-MONTES ALTO DOURO, Radioterapia, Vila 

Real, Portugal 

Purpose: The purpose of this work was to study the behavior of a 2D ion 

chamber array for use in routine linear accelerator (linac) quality control. 

Materials: The device is a Scanditronix Wellhofer I’mRT MatriXXTM 2D array 

with 32x32 ionization chambers, with a distance of 7,619 mm between the 

centers of the chambers. The detector short and medium term reproducibility 

was tested through an extensive set of repeated measurements. The response 

linearity of the system to dose was verified in the range 1-500 MU’s. 

We also tested its sensitivity to millimetric collimator positional changes. Furthermore, 

the output factors were study and compared with measurements 

done with a diode detector for field sizes from 1x1 cm2 to 20x20 cm2. 

Results: The results of the short-term reproducibility were 0.2% and for 

medium-term were approximately 1%. These values include the output fluctuations 

of the linac. The response was found to be linear with dose. We 

were able to detect 1 mm changes in field size but the differences were overestimated 

by 50%. For the output factors differences of 4% were found. 

Conclusions: The results of this study indicate that this type of device is 

suited to perform a number of linac routine quality control tests. The easiness 

of use and short setup time makes them an alternative method as compared 

to ion chambers and films. 

1250 poster 

EVALUATION OF THE CORRECTION FACTOR DUE TO THE 

LACK OF FULL SCATTER CONDITIONS IN CS-137 AND IR-192 

BRACHYTHERAPY DOSIMETRIC STUDIES 

F. Ballester 1 , J. Perez-Calatayud 2 , M. Rivard 3 , C. Melhus 3 , M. Pujades 2 , 

D. Granero 2 

1 

UNIVERSITY OF VALENCIA, Atomic, Molecular, and Nuclear Physics, 

Burjassot, Spain 

2 


3 

TUFTS UNIVERSITY SCHOOL OF MEDICINE, Radiation Oncology, Boston, 

USA 

Purpose: Use of a finite phantom to derive dose rate distributions around 

brachytherapy sources implies a lack of backscattering material near the 

phantom periphery. Conventional planning algorithms and newly-developed 

3D correction algorithms are based on physics data under full scatter conditions. 

Presently, most published Monte Carlo dosimetric studies have been 

obtained using either a spherical phantom (15 cm in radius) or a cylinder 

phantom (40x40 cm 2 ). The study objective was to derive a simple relationship 

to correlate the radial dose function, g(r), obtained for each one of these 

phantoms to that obtained for an unbounded phantom. 

Materials: Assuming bare point sources of 137 Cs and 192 Ir, kerma was calculated 

using Monte Carlo GEANT4 code for 1) a spherical phantom of 40 

cm in radius, R, which is assumed an unbounded phantom for r < 20 cm, and 

2) spherical phantoms of R = 15 cm and R = 21 cm. The later size mimics 

the scatter conditions of a 40x40 cm 2 cylindrical phantom for both radionuclides. 

From the ratio of the dose rate distributions for unbounded/bounded 

phantoms we derived the relationship between g(r) for both phantoms. 

Results: Phantom size correction results to g(r) were obtained and fit to 3rd 

order polynomials (R 2 > 0.999) valid for r < 10 cm, which is the clinical range 

of interest. To validate the method, published dose-rate distributions for two 

137 Cs and 192 Ir sources in bounded/unbounded phantoms were compared 

with the fits of this study. Agreement was typically within 0.2% over all distances 

studied. 

Conclusions: In order to compare the dose rate distributions published for 

different phantom sizes, a simple expression based on fits of the dose distribution 

ratios for bounded/unbounded phantoms was developed for 137 Cs and 

192 Ir. Using these relations, it was possible to correlate g(r) between bounded 

and unbounded phantoms for improved accuracy and consistency of clinical 

dosimetry.

1251 poster 

EXCLUSIVE CONTRIBUTION OF INTERNAL MAMMARY LYMPH 

NODE IRRADIATION TO HEART DOSE RADIATION EXPOSURE IN 

BREAST CANCER 

N. Magné 1 , C. Chargari 1 , P. Castadot 2 , N. Bourgois 2 , P. Van Houtte 2 


2 INSTITUT JULES BORDET, Radiotherapy, Brussels, Belgium 

Purpose: Recommended for high-risk patients, irradiation of the internal 

mammary chain (IMC) remains debated because of additional cardiovascular 

morbidities. However, there are few data on its own contribution to heart 

dose exposure. This prospective study is the first to assess the heart dose 

exposure related to radiotherapy (RT) of internal mammary lymph node. 

Materials: Thirty-six consecutive patients presenting breast cancer with clinical 

or histological indication for IMC irradiation were enrolled onto a prospective 

study, in order to assess the impact of IMC irradiation, in terms of heart 

dose-volume histogram. Four patients groups were defined, according the 

type of previous surgical procedure (mastectomy or lumpectomy) or breast 

cancer laterality. The IMC was treated by usual conformational irradiation 

technique (mean prescribed dose 50 Gy). For each regimen, cardiac dosevolume 

histograms were generated. 

Results: In case of right-sided cancers, the maximal irradiation doses delivered 

to the heart were 24.5 Gy for postlumpectomy radiotherapy versus 

31.2 Gy for postmastectomy irradiation. Patients with left-sided tumours had 

higher mean irradiation doses delivered to the heart (42.7 Gy for breast irradiation, 

versus 42.5 Gy for chest wall irradiation). The D1/3 and D2/3 were 

also significantly increased in case of left-sided cancer, compared with the 

patients suffering with right-sided tumours (10.2 Gy and 2.4 Gy for left-sided 

irradiation, versus 1.2 Gy and 0.9 Gy for right-sided irradiation, respectively). 

Conclusions: Heart dose exposure from right-sided irradiation is far from being 

inconsiderable. As long as low doses of ionizing radiation might have consequences 

on circulatory system, this should be considered by physicians. 

Left-sided IMN irradiation contributed for about 10Gy to cardiac radiation exposure, 

which represents the third of the maximum tolerable dose. 

1252 poster 

FIVE YEARS OF IN-HOUSE SOURCE STRENGTH VERIFICATION 

OF I-125 STRANDED SEEDS 

B. Schrauwen 1 , J. Venselaar 1 

1 DR. B. VERBEETEN INSTITUTE, Medical Physics, Tilburg, Netherlands 

Purpose: International recommendations on QA of brachytherapy underline 

the importance of verification of source strength at each delivery. In most European 

countries there is no easy access to a primary or secondary standards 

laboratory to obtain a traceable absolute calibration system for the low-energy 

I-125 seeds used for early stage prostate treatment. This work demonstrates 

the use and five-year’s experience with a simple and relative measurement 

technique. 

Materials: Since its introduction in 2003, a well-type chamber (Victoreen 

Sweet Spot) is used in our institute for the LDR I-125 seed implant technique 

for prostate patients. Stranded seeds (RapidStrands) are obtained from Oncura. 

A stainless steel insert is constructed for the well-type chamber suitable 

to hold the full RapidStrand. Five seeds expose the chamber while the holder 

shields the other 5 seeds. After a first reading is recorded, the strand is turned 

over and the 2nd reading is recorded of the remaining 5 seeds. Each strand 

used for patients has been measured in this way, always under sterile conditions 

and before the actual insertion of seeds. The reading of the 5 seed/half 

strand was compared with the mean of the readings of the preceding period 

corrected for the activity specified by the vendor. A tolerance level of 5% was 

considered applicable. In addition, all readings of the strands for the same 

patient were averaged and this average reading was again compared, with a 

tolerance level of 3%. In 5 years time, 296 patients were implanted, of which 

2471 strand results were obtained. 

Results: The results from the measurements were analyzed continuously 

over time. In these 5 years, the standard deviation of the 4942 average readings 

(per 5 seeds) was 1.4% (1sd). A time line is constructed showing small 

jumps at given points in time. In total, two striking deviations were encountered. 

In May and in June 2007 we found two patient cases where the 3% 

tolerance level was exceeded. In both patient cases, consistency checks on 

the equipment were made with remaining seeds from previous deliveries. For 

example, individual seeds of one of the strands were measured afterwards, 

showing that 5 seeds had a deviation of >5% while the other 5 seeds were 

in agreement within 1.2%. A total of 6 readings were found where the 5seed/half 

strands showed more than 5% deviation. The patients were in those 

cases inserted as much as possible with seeds from other strands only. The 

vendor was informed about the results. In spite of extensive communications 

between vendor and user, no clear conclusions could be drawn. 

Conclusions: In spite of the lack of easily accessible calibration facilities 

in the EU countries, it is demonstrated that even a simple but accurate and 

consistent relative verification procedure is able to show deviations in the delivery 

of the manufacturer’s sources. Of a total of 296 patients (2471 strands), 

6 out-of-tolerance delivered strands were detected. 

PHYSICS AND TECHNOLOGY : BASIC DOSIMETRY AND DETECTORS 

1253 poster 

S 399 

IMPLANTABLE DETECTORS FOR IN VIVO DOSIMETRY OF EX- 

TRACRANIAL TARGETS DURING RADIOTHERAPY TREATMENTS 

USING THE CYBERKNIFE. 

P. Scalchi 1 , A. Pacheco 2 , C. Cavedon 1 , R. Righetto 1 , M. E. Masterson- 

McGary 2 , S. Cora 1 , P. Francescon 1 , V. Santangelo 1 

1 AZIENDA U.L.S.S. 6, Medical Physics, Vicenza, Italy 

2 NCH REGIONAL CANCER INSTITUTE, Medical Physics, Naples FL, USA 

Purpose: CyberKnife permits Image Guided Hypofractionated Radiotherapy 

of both cranial and extracranial targets with high degree of precision and conformability. 

Image coregistration and tracking allow controlling patient setup 

and following organ motion. Phantom-verified dose accuracy is within 1-2 

mm. However only in vivo dosimetry can provide a final verification of the 

actual patient dose. Due to many CyberKnife beams, traditional methods are 

impractical. An ideal solution could be an implantable detector placed directly 

inside the target volume. This study aims to verify if an implantable dosimeter 

known as DVS (Sicel) can satisfy this purpose. 

Materials: The DVS system consists of implantable (and imageable) MOS- 

FETs detectors coupled with an antenna for wireless connection to a reading 

system. Due to the need for sterilization, the sensors are factory precalibrated. 

The original DVS was designed for use with standard external 

beam treatments. New DVS dosimeters are being developed for use with 

hypo-fractionated dose fractionation (DVS-HFT). For our application, any expected 

dosimetry uncertainty would be mainly due to a discrepancy between 

the factory linac-based calibration and actual Cyberknife treatment characteristics 

(radiation source, dose rate, field-size, angular dependence, dose 

fractionation, irradiation time). Three kinds of phantoms were used in this 

study: a virtual water phantom, a temperature-controlled water phantom (37 

◦ C testing) and a temperature-controlled body phantom. The following was 

investigated: response as a function of field size (collimator set 5 to 60 mm), 

dose rate and dose-per-pulse dependence, dose fractionation dependence 

(using 7, 10 and 12 Gy daily doses), time dependence (irradiation times from 

0.5 to 2.5 h). Finally, simulations of actual prostate treatments were performed 

using the body phantom. All doses were validated and referred to ion 

chamber measurements and/or obtained from the treatment planning system. 

Results: The discrepancies between the measured doses and the reference 

doses were on average within 5%. 

Conclusions: Initial results suggest that it may be possible to use the DVS 

implantable detectors for in vivo dosimetry of extracranial Radiotherapy using 

the Cyberknife system. Additional measurements and testing are needed to 

validate these preliminary results. 

1254 poster 

IN-VIVO DOSIMETRY PERFORMED ON-LINE DURING PDR 

BRACHYTHERAPY BY USE OF SMALL ALUMINIUM OXIDE CRYS- 

TALS 

S. K. Nielsen 1 , K. Tanderup 2 , J. C. Lindegaard 2 , C. E. Andersen 3 

1 


C, Denmark 

2 


Denmark 

3 

RISØ NATIONAL LABORATORY, TECHNICAL UNIVERSITY OF DENMARK, 

Radiation Physics Department, Roskilde, Denmark 

Purpose: Recently brachytherapy has developed from 2D based standard 

loading patterns to 3D image guided treatment plans. This increases the need 

to monitor the delivered dose to avoid misadministration. Currently, however, 

in-vivo dosimetry is difficult due to the size of standard in-vivo dosimeters. 

This presents a problem in the steep gradient field close to or even inside 

a tumour and more sophisticated dosimetry systems are needed. To address 

these issues a new dosimetry system for in-vivo measurements during 

brachytherapy was developed. 

Materials: The new system is based on radioluminescence (RL) and optically 

stimulated luminescence (OSL) from small (0.5 by 2 mm 2 ) carbon-doped aluminium 

oxide crystals (Al2O3:C) attached to 15 m long optical fibre cables. 

Each cable has one crystal, small enough to fit inside a brachytherapy applicator. 

The crystals can be read out remotely during the treatment, and the RL 

signal provides a real-time measurement of the dose rate at the position of 

the crystal. Immediately after the treatment, the OSL signal then gives the absorbed 

dose. We use an Ir-192 source from the GammaMed Plus afterloader 

unit, Varian. We have tested the system on five patients using different applicator 

types. In each case at least one crystal was placed in a needle close to 

or inside the tumour and once a probe was also placed in the patient’s rectum 

along with our usual diode rectal probe. 

Results: Feasibility of the system for patient in-vivo dosimetry was demonstrated 

in five patients treated with pulsed dose rate brachytherapy (PDR-BT) 

over 10-50 hours. One patient was treated interstitially with 15 needles for a 

supra vaginal recurrence of cervical cancer, the other four where treated for 

cervical cancer using a combination of the intracavitary ring/tandem applicator 

system and needles. For each pulse both the dose rate and the total dose 

were measured. The measured dose rate was compared with calculations of


the expected signal and good agreement was found. Both the RL signature 

for each pulse and the total dose per pulse obtained from the OSL signal 

remained stable throughout the treatments. 

Conclusions: In conclusion we have developed a new system that allows for 

intra-tumoral on-line dosimetry and monitoring of brachytherapy by minute 

patient friendly equipment. The perspective is to integrate this system in 

the clinic, enabling surveillance of the progression of PDR-BT with automatic 

warning if the measured dose rate differs unacceptably from the expected. 

1255 poster 

INVESTIGATING LITHIUM FORMATE EPR DOSIMETRY FOR 

ABSOLUTE DOSE MEASUREMENTS AROUND 192IR SOURCES 

L. Antonovic 1 , H. Gustafsson 1 , E. Lund 1 , G. Alm Carlsson 1 , Carlsson 

Tedgren 1 

1 LINKÖPING UNIVERSITY, IMH Radiation Physics , Linköping, Sweden 

Purpose: The aim of this work was to investigate lithium formate monohydrate 

(LiFo) that is a new material for EPR (Electron Paramagnetic Resonance) 

dosimetry, for absolute dose measurements around 192Ir brachytherapy 

sources. LiFo is of interest in having a density and mass energy absorption 

properties closer to water than the established material for TL (Thermo 

Luminescence) dosimetry, Lithium Flouride (LiF). LiFo is 2-6 times more sensitive 

(depending on read-out procedure) than alanine, a common material 

for EPR dosimetry. The photon spectrum around 192Ir sources varies significantly 

with distance from the source and is known to significantly affect the 

response (signal per unit absorbed dose in water) of LiF dosimeters. 

Materials: LiFo was mixed with 10% paraffin and manually pressed into 

tablets according to a routine previously used for external beam applications. 

Calibrations for absolute dosimetry were performed in a high energy photon 

beam. The 192Ir irradiations were performed with the dosimeters positioned 

in a solid phantom of PMMA at distances 1, 3 and 5 cm from the centre. In order 

to reduce dose gradients in this initial test of the LiFo material, the brachy 

source was stepped linearly through the centre of the phantom. For comparison, 

measurements were also performed using similarly sized LiF TL dosimeters. 

Monte Carlo simulations of the photon energy spectrum were performed 

and calculated and measured responses compared for both dosimetry systems 

to aid in the analysis of the experimental data. 

Results: Values of absorbed dose to water determined with the LiFo system 

agreed with those determined by the treatment planning system within the 

estimated uncertainties that ranged from 3-7% at the investigated distances 

(coverage factor k=1). LiFo is less sensitive than TL and needs to be irradiated 

with doses above around 2 Gy to get a comparable precision. The LiFo 

material has a linear dose response over a wide dose range (up to 1000 Gy) 

which means that the variation in dose with distance from a brachytherapy 

source or implant is not a problem and can be determined in the same irradiation. 

With LiF, dosimeters closest to the source may need to be redrawn 

from the phantom after some time in order to avoid too high doses. 

Conclusions: The LiFo EPR material can be used to measure absolute 

doses around 192Ir brachytherapy sources with an accuracy comparable to 

that of LiF TL, provided correction for the energy response can be made. The 

LiFo system has an advantage in situations where this is not possible due to 

lack of full information of the photon energy spectrum, such as when used for 

experimental verifications of arbitrary multiple source irradiations. 

1256 poster 

KILOVOLTAGE X-RAY DOSIMETRY - AN EXPERIMENTAL COMPARI- 

SON BETWEEN DIFFERENT DOSIMETRY PROTOCOLS 

P. Munck af Rosenschöld 1 , T. Knöös 1 , P. Nilsson 1 


Purpose: Kilovoltage dosimetry protocols by the IAEA (TRS 277 and 398), 

DIN (6809), IPEMB (with addendum), AAPM (TG-61) and NCS (report 10) 

were compared experimentally in four clinical beams. The purpose of the 

study was to investigate if the application of the protocols results in dosimetric 

differences of clinical significance. 

Materials: The beams had acceleration potentials of 30, 80, 120 and 200 

kV, with half-value layers ranging from 0.6 mm Al to 1 mm Cu. Dosimetric 

measurements were performed and data were collected under reference 

conditions as stipulated within each separate protocol under investigation. A 

Monte Carlo method (EGSnrc) was used to derive back-scatter factors for the 

actual x-ray machine. 

Results: In general, the agreement of the dosimetric data at the surface of 

a full-scatter water phantom obtained using the guidelines of the various protocols 

was fairly good, i.e. within 1-2% (see Table 1). However, the in-air 

calibration method using the IPEMB and AAPM TG-61 protocols yielded an 

absorbed dose about 7% lower than the IAEA TRS-398 protocol in the 120 kV 

beam. By replacing the back-scatter factors given in the protocols with Monte 

Carlo calculated back-scatter factors the convergence between the protocols 

improved (within 4%). Table 1. Absorbed dose to water (Gy/100MU) at the 

surface of a full-scatter phantom; comparison between air kerma and absorbed 

dose to water based protocols. Measurements are normalized to the 

average of each column. "Geometry" refers to the reference conditions for 

determination of absorbed dose to water: "in-air" represents air kerma measured 

free in air requiring the use of a back-scatter factor; "0 cm" represent 

absorbed dose measured at the surface of a full-scatter phantom; "2 cm" 

represents absorbed dose measured at 2 cm depth in water. 

Conclusions: The present study shows that the current supported dosimetry 

protocols in the kilovoltage range were in fairly good agreement, and there 

were only a few exceptions of clinical significance. 

1257 poster 

PERFORMANCE OPTIMIZATION OF THE INTEGRATED ACQUISI- 

TION MODE OF THE VARIAN AS500-II EPID AND INVESTIGATION 

FOR MEASUREMENT OF ENHANCED DYNAMIC WEDGE. 

Z. Al kattar 1 , J. N. Foulquier 1 , E. Touboul 1 

1 TENON HOSPITAL, Radiation Physics, Paris 20, France 

Purpose: To better understand the image acquisition operation of an EPID 

and to evaluate the dosimeter properties in treatments with enhanced dynamic 

wedges. 

Materials: The Work presented rests on the study of the Varian EPID: aS500- 

II and the Image Acquisition system IAS3. We are interested in integrated 

image acquisition mode not synchronized to the accelerator beam pulses. 

We investigated the influence of the Frame Cycle Time "FCT" parameter on 

the gray level, the speed of acquisition and the noise in the image, according 

to the energy of the X-ray beams (6 and 15 MV) and the Clinac 2100 C/D 

dose rate. We also studied the performances, stability and the reproducibility 

of the EPID aS500-II in measurements of the wedge factors of the fields with 

enhanced dynamic wedges. 

Results: In this mode, only one parameter the "FCT" influences the pixel 

value. The pixel value is directly proportional to this parameter PV = N x Rs -1 

x FCTs (N: number of frames, R: response of the detector /s) . When the FCT 

> 55 ms , the speed of acquisition is inversely proportional to this parameter 

Vf/s = FCTs -1 . The noise lies between 0.2% and 0.5%. We determined a 

rule to avoid saturation. Due the reproducibility of the EPID measured EDW 

factors the device is highly suited in this mode of acquisition to regular measurement 

of EDW. EPID measurements were found to exhibit a dependence 

on the wedge direction and EPID position. An empirical correction function 

was developed to correct the wedge profiles. 

Conclusions: The choice of the acquisition parameters is essential for the 

complete detection of radiations and especially to use this detector as a 

dosimeter. 

1258 poster 

SENSITOMETRIC CURVES OF RADIOCHROMIC DOSIMETRY 

FILMS FOR RADIOTHERAPY VERIFICATION 

K. Chelminski 1 , W. Bulski 1 , D. Georg 2 , D. Bodzak 1 , M. Fuss 2 , D. 

Oborska-Kumaszynska 3 , Z. Maniakowski 4 , J. Rostkowska 1 , M. Kania 1 , 

A. Walewska 1 , M. Zalewska 1 

1 

THE MARIA SKLODOWSKA-CURIE MEMORIAL CANCER CENTER, Medical 


2 

UNIVERSITY OF VIENNA MEDICAL SCHOOL, Department of Medical 

Radiation Physics, Vienna, Austria 

3 

LOWER SILESIAN ONCOLOGY CENTER, Medical Physics Department, 

Wroclaw, Poland 

4 

MARIA SKLODOWSKA-CURIE MEMORIAL CENTER OF ONCOLOGY, Medical 

Physics, Gliwice, Poland 

Purpose: The purpose of the study was determination of sensitometric 

curves for new types of radiochromic films in order to asses their potential 

use in Intensity Modulated Radiotherapy (IMRT) verification. Investigation of 

energy dependence of the sensitometric characteristics was performed. The 

questions which had to be answered were: Are the sensitometric curves energy 

dependent? What is the influence of the signal level recorded on the 

films on the dose readout uncertainty? Is the dose readout dependent on 

orientation of the films during digitization? 

Materials: GafChromic EBT and RTQA films (International Specialty Products, 

USA) were irradiated by several photon beams generated by Co-60 unit,

PHYSICS AND TECHNOLOGY : DOSE CALCULATIONS (MONITOR CALC, MONTE CARLO, TPS) 

and by linear accelerators in the energy range 4-25MV. The films were digitized 

using EPSON flat-bed scanner. FilmQA (3cognition, USA) software was 

used for determining the sensitometric curves. Each point of the sensitometric 

curve was determined as a mean pixel value from scanned 4 cm2 region 

of the film irradiated with known dose. 

Results: The mean pixel values for points of sensitometric curves differ about 

10% over the whole range of energy. However, the differences of the pixel 

values are more significant for doses up to 50 cGy for which the influence 

of the scanner is more pronounced due to low optical densities of the films. 

The digitization orientation dependence on the readout of the pixel value was 

observed for EBT type films. 

Conclusions: Radiochromic films seem to be useful tool for IMRT verification 

due to low energy dependence of the sensitometric curve. However, relatively 

high readout uncertainty may be expected using a flat-bed scanner for doses 

below 50 cGy. The advantages of the use of radiochromic films are related 

to uniform sensitivity to radiation from different X-ray beams and to very low 

sensitivity for the room light. The disadvantages are scanning orientation 

dependence of EBT type films and very low optical density which generates 

high readout uncertainty from films irradiated with doses below 50 cGy. 

1259 poster 

TEST OF ELECTROMETERS FOR DOSIMETRY SYSTEMS 

B. Blad 1 , P. Munck af Rosenschöld 1 , I. Kristensen 1 


Purpose: Dosimetry systems, which normally consist of an ionisation chamber 

and an electrometer, have to be checked regularly in order to maintain 

their characteristics. Calibration is performed regularly at National Standard 

Laboratories and locally by using radiation from a radiation source. However, 

normally the dosimetry system is calibrated as a unit. Therefore a calibration 

procedure for only the electrometers is valuable. The aim of this work is 

to calibrate electrometers at the department used in dosimetry systems. In 

regard to similar currents and times used during normal use. 

Materials: A Keithley 6221 (DC and AC current source) has been used as a 

reference current source. Currents of different magnitudes and durations can 

be generated. According the source specification the accuracy is: ±0.4 % 

+ 2 fA at range 2 nA and ±0.3 % + 10 fA at range 20 nA. Electrometer test 

have been performed at 1nA in 100 s equal 100 nC. The tested instruments 

are 5 Elektra from Precitron, two Unidos from PTW. The electrometers were 

connected via a driven screen cable in order to minimise measurement errors. 

All the instruments, including the generator, were left on several hours before 

measurements. Measurements were performed at several occasions. 

Results: Small differences were observed between the different electrometers. 

The results are presented in table 1, where the calibration constant, 

kelec = charge from the generator / measured charge. Since the accuracy of 

the generator is limited these checks is mainly intended for finding incorrect 

electrometers. Compensation of difference in sensitivity of the electrometers 

can only be made if the accuracy of the generator is considered. Good correlation 

can be observed between the measurement made locally and at the 

Standard laboratory. Three of the instruments were calibrated at SP, Technical 

Research Institute of Sweden. 

Conclusions: A simple current generator can be used for testing electrometers. 

1260 poster 

THE ROLE OF IN VIVO DOSIMETRY IN MODERN RADIOTHERAPY 

W. Bulski 1 , J. Rostkowska 1 , M. Kania 1 , A. Walewska 1 

1 CENTRE OF ONCOLOGY, Medical Physics Department, Krakow, Poland 

Purpose: The aim of this study was to revise the value of in vivo dosimetry in 

high tech radiotherapy. The measurements of entrance dose are discussed 

in this paper. The measurements of entrance dose became a standard procedure 

in the early nineties and are up to now a compulsory quality assurance 

procedures in many countries. However, since then the technology of 

S 401 

radiotherapy developed so much that the relevance of entrance dose measurements 

should be revised. 

Materials: During the period 2004-2007 in vivo dosimetry measurement were 

carried out on 7 Varian accelerators networked to the Varis Record and Verification 

[R&V] system. The measurements were performed for about 7000 

patients undergoing 3D conformal radiotherapy with MOSFET 20 System detectors 

(about 6500 patients) and semiconductor diodes from Scanditronix 

(about 500 patients). Tolerance limits were ±5% for open fields and ±7% for 

wedged fields (physical and dynamic). 

Results: In about 20% of cases the results were beyond the tolerance limits. 

However, after the repeated measurements the results remained beyond 

tolerance limits only in 3 cases, which is less than 0.05%. All 3 cases were 

detected on the accelerator which was not networked into the R&V system 

(the block trays were not accounted for in the calculations). 

Conclusions: The revue of literature and our own experience prove that in 

vivo dosimetry with available detectors characterized by somewhat limited accuracy, 

and therefore the tolerance limits as high as 5-7%, show that very few 

errors may be detected. In most studies the rate of errors over the tolerance 

limit is of the order of 1%, and almost all these errors are caused by wrong 

detector placement. It seems that the cost in terms of equipment, manpower 

and time consumed involved in the procedure does not justify the effort. The 

detailed costs of the measurements are now being evaluated. Moreover, in 

most precise and demanding techniques such as stereotaxy and IMRT the 

role of in vivo dosimetry is still not defined. The manpower involved could 

be better used for more thorough quality assurance procedures in equipment 

testing.It may be concluded that in vivo dosimetry should be limited to selected 

cases and to the implementation of new techniques in the department, 

and should not be compulsory in quality assurance regulations. 

1261 poster 

TLD AUDITS FOR MLC-SHAPED IRREGULAR FIELDS IN RADIO- 

THERAPY CENTRES IN POLAND 

J. Rostkowska 1 , W. Bulski 1 , M. Kania 1 , B. Gwiazdowska 1 , M. Zalewska 1 

1 CENTRE OF ONCOLOGY, Medical Physics Department, Krakow, Poland 

Purpose: The Secondary Standard Dosimetry Laboratory (SSDL) of the 

Medical Physics Department of the Centre of Oncology in Warsaw has become 

a member of the IAEA/WHO international network of such laboratories 

in 1988. The SSDL has been carrying-out the external postal TLD audits in 

teletherapy centres since 1991. Regular yearly audit runs have been carried 

out in reference conditions. Regular yearly audit runs have been extended to 

non-reference conditions since 2003. The results of selected runs are presented. 

Materials: TLD system consists of PCL3 TLD automatic reader and 

Niewiadomski &Co. (LiF:Mg,Ti) powder. TLD runs for on axis measurements 

in non-reference conditions were performed in Co-60, X-ray and electron 

beams. The TLD were irradiated at 10 cm and 5 cm depth for open 

fields (8x8, 10x10, 10x20 cm 2 ) and wedge field (10x10 cm 2 ) in Co-60 and 

X-ray beams. In electron beams the TLD were irradiated at depth of dmax for 

6x6 cm 2 and 10x10 cm 2 fields. Pilot studies were performed in order to test 

the methodology for the dosimetry measurements and the documentation for 

the practical operation of the audit system in a variety of non-reference conditions: 

off-axis (symmetric and asymmetric fields) and for fields formed by 

MLC. The nation-wide runs of the on axis measurements for MLC-shaped 

irregular fields have been performed. 

Results: The results of the audit in non-reference conditions for on axis measurements 

are in the majority o cases within the 3.5% tolerance limit which 

is usually used for reference conditions. The results of the pilot study for offaxis 

(symmetric and asymmetric fields) measurements and measurements 

for fields formed by MLC show that it is possible to keep the dose determination 

within tolerance limits by the implementation of correct methodology and 

carefully carried-out measurements and calculations of doses. The nationwide 

audit, off axis for MLC-shaped fields, show that measurements may be 

held within the ±5% limit. 

Conclusions: The methodology and results of the audit permit to introduce 

and maintain the audit program in non-reference conditions, for on-axis and 

off-axis measurements, at the national level. 

Physics and technology : Dose 

calculations (monitor calc, Monte 

Carlo, TPS) 

1262 poster 

A MULTIPLE SOURCE MONTE CARLO MODEL DEVELOPED FOR 

SIMULATING THE CLINICAL ELECTRON BEAMS OF NEPTUN 10PC

S 402 PHYSICS AND TECHNOLOGY : DOSE CALCULATIONS (MONITOR CALC, MONTE CARLO, TPS) 

MEDICAL LINAC 

B. Hashemi 1 , N. Jabbari 2 

1 

TARBIAT MODARES UNIVERSITY, Medical Physics, Tehran, Iran Islamic 

Republic of 

2 

UROMIA UNIVERSITY OF MEDICAL SCIENCES, Radiology, Uromia, Iran 

Islamic Republic of 

Purpose: To achieve high accuracy from a Monte Carlo dose calculation, 

detailed information of the beam characteristics is required. Some common 

Monte Carlo codes provide this through a phase-space output file demanding 

high disk space and CPU time. Using multiple-source models is an alternative 

saving disk space and CPU time. The aim of this study was to develop an 

accurate multiple-source model for NEPTUN 10 PC linac. 

Materials: The BEAMDP (BEAM Data Processor) Monte Carlo code was 

used to develop the source model. This code utilizes the BEAMnrc-based 

phase space information of the linac scored at the patient plane. The BEAMnrc 

code was used to simulate the linac treatment head. Monte Carlo calculations 

for all of the linac electron beams (6, 8 and 10 MeV) were performed 

at the reference field size (100 cm 2 ) and 100 cm SSD. All components of the 

treatment head were modeled as sub-sources for the electron beams. An initial 

number of 10 +7 histories was used to ensure good statistical uncertainty 

(mostly better than 1% (1SD)) in the forthcoming absorbed dose calculations. 

The constant values of AE=ECUT=0.7 MeV and AP=PCUT=0.01 MeV were 

used for all the component modules in the BEAMnrc simulations with the exception 

of scoring the phase-space file for which the cutoff energies of the 

next component must be set to some high values to prevent the backscatter 

radiation from the phantom. Central axis depth-dose curves and dose profiles 

for the electron beams were measured at the reference field and 100 cm SSD 

with diode detectors in an RFA 300 water phantom. Comparison of the NEP- 

TUN 10PC electron beam measurements with the central-axis depth-dose 

and dose profiles calculated from the original phase-space file showed good 

agreement. The corresponding phase-space data enabled us to characterize 

several sources representing the main components of the beam defining 

system. The full source model was used to generate Monte Carlo dose distributions 

and compare them with those calculated with the full phase space 

data for the electron beams. 

Results: The calculated dose distributions in the water phantom were in good 

agreement with those calculated using the original phase-space file for the 

full source model with an accuracy about 1%. In addition, the agreement 

between the experimental data and calculated data from the phase space file 

was good within 0.5% to 1% accuracy. 

Conclusions: The results showed that the multiple source model provides 

accurate results in Monte Carlo dose distribution calculations. The disk space 

requirements for the source model is considerably less compared to that for 

the full phase space beam. In addition, the overhead computing time for the 

electron beam reconstruction is negligible. 

1263 poster 

ABSORBED DOSE DISTRIBUTIONS IN THE VICINITY OF HIGH- 

DENSITY MATERIALS IN HEAD AND NECK RADIOTHERAPY: 

A QUANTITATIVE COMPARISON BETWEEN MEASUREMENTS, 

MONTE CARLO SIMULATIONS AND TREATMENT PLANNING DATA 

U. Bjelkengren 1 , S. Bäck 2 , E. Wieslander 3 , L. Wittgren 4 

1 COPENHAGEN UNIVERSITY HOSPITAL HERLEV, Herlev, Denmark 

2 LUND UNIVERSITY, MALMÖ UNIVERSITY HOSPITAL, Malmö, Sweden 

3 UNIVERSITY HOSPITAL LUND, Lund, Sweden 

4 MALMÖ UNIVERSITY HOSPITAL, Medical Radiation Physics, Malmö, 

Sweden 

Purpose: The introduction of high-density materials in the head and neck region 

will lead to discrepancies between planned and delivered absorbed dose 

for patients undergoing radiotherapy. These discrepancies occur due to large 

differences in density between the oral tissue and dental materials which also 

introduce image artifacts in the CT-images used for radiotherapy treatment 

planning. This could introduce additional uncertainties. The purpose of this 

study was to quantify the absorbed dose in the vicinity of high-density materials 

and to compare the results with treatment planning data to assure that 

the patient was given an optimal treatment. 

Materials: Dental materials were placed at 37 mm depth in a custom built 

water filled phantom and irradiated using a photon beam quality of 6 MV. A 

compact ionization chamber (CC01, IBA Dosimetry) was used to measure 

depth dose curves in front and beyond the high-density dental material. Corresponding 

Monte Carlo data as simulations were obtained using the EGSnrc 

user code DOSXYZnrc and used for reference. The dental materials studied 

were composite, porcelain, titanium and a 75 % gold alloy. The sizes of the 

dental materials were 1 cm3 except for the gold alloy that was 0.26 cm3. A 

computer generated phantom equal to the water filled phantom was created 

in the treatment planning system (TPS Master Plan v1.5, Nucletron). Two 

different calculation methods were evaluated, the pencil beam and the collapsed 

cone algorithms. In this study two CT scanners from different vendors 

were evaluated, GE HiSpeed and Siemens Sensation 64. 

Results: The compact ionization chamber data showed good agreement with 

the Monte Carlo simulations for all materials. A large difference was found 

between the TPS calculations and the measurements, especially in the case 

of the gold alloy (see figure). For the composite, porcelain and titanium cases 

an underestimation of 3.1, 4.7, and 5.8 % in absorbed dose was found at 5 cm 

depth. Differences of up to 8.8 % in absorbed dose were found between the 

two calculation algorithms. Differences of up to 700 HU was found between 

the CT-scanned dental materials and the Hounsfield scale implemented in the 

TPS for electron density calculation. A 3.0 % difference in absorbed dose was 

found at 5 cm depth for the gold alloy between the two different CT-scanners. 

Conclusions: The underestimation of absorbed dose in front of high-density 

materials due to backscattered contaminating electrons can not be neglected. 

The collapsed cone is the preferable dose calculation algorithm of the two 

evaluated. CT-scanners must be evaluated to find the most suitable filters and 

reconstruction algorithms to minimize image artifacts. Limitations in the TPS 

regarding assigning electron density and maximum density lead to additional 

uncertainties in the vicinity of high-density cavities. 

1264 poster 

ACCURATE LUNG DOSE DETERMINATION WHEN USING PARTIAL 

TRANSMISSION BLOCKS FOR STAGE IV NODULAR SCLEROSING 

HODGKIN’S LYMPHOMA 

J. Musgrove 1 , J. Winston 1 , A. Gupta 1 , J. Herrada 2 

1 

EL PASO CANCER CENTER, Radiation Oncology, El Paso, Texas, United 

Kingdom 

2 

TEXAS TECH UNIVERSITY, Medical Oncology, El Paso, Texas, USA 

Purpose: A 15 year-old male was diagnosed with Stage IVB nodular sclerosing 

Hodgkin’s lymphoma with metastatic bilateral pulmonary nodules. Protocols 

for Hodgkin’s lymphoma have required the use of partial transmission 

blocks for the lungs to prevent complications. The protocol requires that the 

dose be determined without inhomogeneity corrections. Our purpose was to 

deliver a 50% median dose to the lungs and to compare calculated doses to 

measured doses in a homogenous phantom. The calculated doses were also 

compared with and without inhomogeneity corrections. 

Materials: Dose distributions for 50% lung transmission blocks have been 

compared using dose distributions from the Eclipse treatment planning system 

(TPS), film dosimetry and diode arrays. The block transmission value in 

the TPS was modified to achieve a median dose to the lung on a dose volume 

histogram of below 50%. The dose to the lung using a 50% transmission 

block was greater than 50% due to internal scatter. The actual transmission 

required to obtain a median dose of approximately 50% was found to be 43%. 

Results: In order to achieve a transmission value of 43% in a homogeneous 

phantom, 1.5 millimeters of lead were added to the 50% transmission blocks. 

The dose distribution of the treatment blocks with the additional lead was 

measured using the above methods in a solid water phantom and compared 

with a 2D isodose map of the field generated by the TPS. Cross-sectional 

dose profiles at multiple areas in the field were examined. The analysis 

showed that the fields produced with the blocks closely matched the planned 

fields. 

Conclusions: Additional dosimetry proved valuable for successfully designing 

the treatment fields and determining the dose distribution under the partial 

transmission blocks to meet protocol requirements. Inhomogeneity calculations 

show a significant increased dose to parts of the lung as expected. 

1265 poster 

AN INVESTIGATION ON THE LINAC WEDGE FACTOR DEPEN- 

DENCE ON THE DEPTH, FIELD SIZE, AND OFF-AXIS USING 

MONTE CARLO METHOD 

B. Hashemi 1 , P. Hejazi 1 , M. Shahriari 2 , M. T. Eivazi 3 , A. Kazemnejad 4 

1 

TARBIAT MODARES UNIVERSITY, Medical Physics, Tehran, Iran Islamic 

Republic of 

2 

SHAHID BEHESHTI UNIVERSITY, Department of Nuclear Engineering, 


3 

KERMANSHAH UNIVERSITY OF MEDICAL SCIENCE, Medical Physics, 

Kermanshah, Iran Islamic Republic of 

4 

TARBIAT MODARES UNIVERSITY, Department of Biostatistics, Tehran, Iran 

Islamic Republic of 

Purpose: Dependence of the wedge factor of the internal wedge of an Elekta 

linac on the depth, field size, and off-axis for the 6MV photon beam has been 

investigated using Monte Carlo method. This has been done for symmetric 

as well as asymmetric fields. 

Materials: The head structure of an Elekta Linac was simulated with and 

without the internal wedge using Monte Carlo method. It was then benchmarked 

against experimental measurements. Thereafter, a standard water 

phantom and a mini phantom were simulated. Then, the linac wedge factor 

was determined for symmetric square field sizes of 4, 5, 10, 15, and 20 cm 2 

at a depth ranged from 0.5 to 34 cm. The simulated wedge factor was compared 

with that measured at 100 cm SAD for each field size. Then, one of the 

jaws was closed once at 1.7 cm (0.85 cm off-axis) and again at 3.5 cm (1.75 

cm off-axis) distance. This was done first toward the toe and then toward the 

heel side of the wedge. Then, the corresponding wedge factor resulted for


every situation of these asymmetric fields was determined. 

Results: Calculated values of the wedge factor for the symmetric fields were 

within 0.75% of the measured values. The results indicated an increase of the 

wedge factor up to 1.2% and 2% in the water and mini phantom respectively 

for the asymmetric fields. It was also noted that the wedge factor can change 

up to 5.2% and 2.7% for the 1.75 and 0.85 cm off-axis situations respectively 

compared to the common asymmetric fields (without off-axis for the same 

field size). The wedge factor in air and water showed a difference up to 0.9%. 

Similar to previous reported studies, analysis of our results suggests a general 

linear dependence of the wedge factor on the depth. Fitted trend lines 

indicate a dependence of the wedge factor on the direction and level of the 

off-axis for the 6 MV photon beam. 

Conclusions: The internal wedge has a fixed position in the photon beams. 

But, the variation of the beam direction can influence the beam output resulted 

from this structure. On the other hand, the beam output is also dependent 

on the field size and depth. The variation of the photon beam due 

to these circumstances can be determined accurately using Monte Carlo 

method. These can be taken into account in clinical practices to reduce the 

level of systematic errors. 

1266 poster 

ANALYSIS OF ELEKTA PRECISE BEAM MODELLING DATA FOR A 

COMMERCIAL ELECTRON MC DOSE CALCULATION ALGORITHM 

M. Arends 1 , A. H. Ausma 1 , E. Traneus 2 

1 

RADIOTHERAPEUTIC INSTITUTE FRIESLAND, Radiotherapy, Leeuwarden, 

Netherlands 

2 

NUCLETRON SCANDINAVIA AB, Uppsala, Sweden 

Purpose: To verify by Monte Carlo simulations and measurements the extension 

of an electron beam model for clinical electron beams to model beams 

collimated by Elekta circular applicators (3 to 5 cm diameter steel cylinders 

used with a small or no air-gap for treating shallow tumours). The beam model 

is implemented in a research version of the Oncentra MasterPlan treatment 

planning system by Nucletron B.V. 

Materials: The beam model is derived from a coupled multi-source electron 

beam model used for beams collimated by an applicator with an optional 

insert. In the extended beam model the phase space is reconstructed by 

sampling from an exit phase space (EPS) located at the entrance of the cylinder. 

The EPS is characterized by the same procedures as used for applicator 

collimated beams as specified in the system documentation. On request 

from the Monte Carlo dose engine (VMC++) electrons are sampled from the 

EPS and transported by 3 to 8 in-air multiple scattering steps from the EPS 

plane down to the exit of the cylinder. Electrons that hit the cylinder wall are 

absorbed and may, with a certain probability, give rise to out-scattered electrons. 

These are sampled from pre-calculated scatter kernels and are then 

transported further through the cylinder. To evaluate the implementation a 

set of beam phase spaces was simulated by BEAMnrc for a detailed model 

of the entire Elekta Precise treatment head. Water dose distributions were 

compared with BEAMnrc simulations, calculations by the treatment planning 

system and measurements for seven energies ranging from 4 to 18 MeV. 

Profiles on the two main axes at two depths (approximately depth of dose 

maximum and brehmstrahlungsdepth) and a percentage depth dose profile 

were compared. All water phantom measurements were performed with a 

p-type electron diode (Scanditronix Wellhfer). 

Results: An excellent agreement with the majority of dose points on the 

1%/1mm level between the measurements and the BEAMnrc simulations was 

obtained. A similar agreement is demonstrated for the treatment planning 

system calculations using the extended beam model for water profiles, depth 

doses and output factors at different air-gaps. 

Conclusions: The Oncentra MasterPlan beam model extension for the 

Elekta circular applicator yields dose calculations that are of adequate accuracy 

for routine clinical use. 

1267 poster 

BETA RAY POINT SOURCE DOSE DISTRIBUTIONS US- 

ING GATE/GEANT4. APPLICATION TO A 106RU OCULAR 

BRACHYTHERAPY TREATMENT. 

L. Maigne 1 , C. O. Thiam 1 , D. Donnarieix 2 , V. Breton 1 

1 LABORATOIRE DE PHYSIQUE CORPUSCULAIRE, PCSV, Aubière, France 

2 CENTRE JEAN PERRIN, Unité de physique médicale, Clermont Ferrand, 

France 

Purpose: Radial distributions of dose around isotropic point sources of electrons 

or beta emitters in an infinite water medium, or dose-point-kernels are 

the basis of many dosimetry problems for medical applications. In ocular 

brachytherapy, dose deposited from 106-Ru ophthalmic applicators of a given 

shape and of a given dimension can be derived from the calculation of dose 

point kernels. Analytical methods fail to account for the 3D nature of radiation 

transport and all relevant energy deposition processes. Monte Carlo 

simulations of dose point kernels is the only practical method for calculation 

that can consider all interactions of importance for the transport of secondary 

S 403 

particles. 

Materials: In GATE/GEANT4 simulations, the dose around a point source is 

obtained by scoring the energy deposited in thin concentric spherical shells 

around the source per particle decay. In the calculations, the energy scored 

in a spherical shell delimited by the radii R1 and R2 divided by the shell mass 

is taken as the dose at some effective radius of the shell R1


1269 poster 

CC VERSUS PB ALGORITHM IN DIFFERENT PATHOLOGIES - 

CLINICAL IMPLICATIONS 

J. Mateus 1 , T. Ventura 1 , M. D. C. Lopes 1 , B. Costa Ferreira 2 

1 



2 

I3N- UNIVERSIDADE DE AVEIRO, Fisica, Aveiro, Portugal 

Purpose: To evaluate the differences between two dose calculation algorithms: 

Pencil Beam (PB) and Collapsed Cone (CC) for different pathologies 

and to assess possible clinical implications. According to the accuracy of the 

calculated dose distribution and the calculation time, it was also intended to 

seek which algorithm in the different pathologies should be adopted on the 

clinical routine. 

Materials: A retrospective study was performed selecting at least 10 cases 

for each of the pathologies: lung, oesophagus, head and neck (H&N), breast, 

prostate and central nervous system (CNS). The plans used for clinical treatment 

and computed with PB, were re-calculated with CC and re-prescribed 

without any further optimization in Oncentra MasterPlan (v. 3.1). To evaluate 

the effect of algorithm differences on patients that have already been treated 

with the number of monitor units (MUs) calculated by PB, a correction factor, 

based on the ratio of the MUs determined by the 2 algorithms, was applied 

to the CC data (CC corrected). From the dose volume histograms (DVH) the 

maximum (Dmax), mean (Dmean) and minimum (Dmin) doses were determined 

for the planning target volume (PTV) and relevant organs at risk (OAR). 

All dosimetric comparisons were made taking CC as the gold standard. 

Results: In almost all clinical cases the dose homogeneity in the PTV is 

lower in the CC than in the PB (see fig.). This comes mainly from the lower 

Dmin calculated by CC, which may influence tumour control but may have a 

beneficial effect on the OARs. The difference in the number of MUs calculated 

by both algorithms depends on the pathology, ranging from 1.5 % for breast 

to 5.1% for lung. Thus the Dmin actually delivered to the PTV may have 

been even smaller than initially estimated by the CC not corrected. After 

applying the correction factor for the MUs, differences in Dmin higher than 

10% were observed for patients with lung, oesophagus and breast tumours. 

In these cases significant tissue heterogeneities are present and then the 

more accurate dose calculation computed by CC is needed. For the other 

pathologies, i.e. H&N, prostate and CNS, no significant dosimetric differences 

were obtained, between the two algorithms. 

Conclusions: Significant differences between the compared algorithms were 

obtained for lung, oesophagus and breast. For these cases the CC will be 

implemented in the clinical routine as the dose calculation algorithm. A reoptimization 

of the plans is then necessary to improve the value of Dmin in 

the PTV. 

1270 poster 

CELLULAR S-VALUES GENERATED WITH THE MONTE CARLO 

CODES PENELOPE, MCNPX AND GEANT4 

H. Uusijärvi 1 , N. Chouin 2 , M. Bardiès 2 , J. M. Fernández-Varea 3 

1 LUND UNIVERSITY, Clinical Sciences in Malmö, Malmö, Sweden 

2 UNIVERSITÉ DE NANTES, Faculté de Médecine, Nantes, France 

3 UNIVERSITAT DE BARCELONA, Facultat de Fisica (ECM), Barcelona, Spain 

Purpose: S-values are the absorbed dose to the target per unit cumulated 

activity in the source and are used in nuclear medicine dosimetry. S-values 

for many organs, as well as for various cell dimensions have been published 

by, e.g., the Medical Internal Radiation Dose (MIRD) committee. The aim of 

this work was to simulate cellular S-values with three general-purpose Monte 

Carlo (MC) codes, namely PENELOPE, MCNPX and GEANT4. Comparisons 

with S-values calculated using scaled dose point kernels generated 

with these codes were also done. 

Materials: S-values were simulated with the MC codes PENELOPE 2006, 

MCNPX 2.5.0 and GEANT4 4.8.2. PENELOPE implements a mixed simulation 

scheme: from detailed (event-by-event) to condensed simulation; in 

this study, detailed simulation was adopted. In turn, MCNPX and GEANT4 

employ a condensed history scheme. The radii of the spherical cell and its 

concentric nucleus were 6 µm and 4 µm, respectively. The nucleus was the 

target and the activity was assumed to be distributed uniformly either in the 

nucleus, the cytoplasm or on the cell surface. S-values were calculated for 

electrons with energies of 10 keV, 100 keV, 500 keV and 1 MeV. 

Results: The S-values generated by the three MC codes agree to within 

6% when the activity is distributed in the nucleus. Differences appear as the 

electron source is farther away from the nucleus:

1272 poster 


COMMISSIONING AND VALIDATION OF SMALL FIELDS IN STEP- 

AND-SHOOT IMRT 

N. Andræ 1 , I. Toma-Dasu 2 , P. Björk 1 , M. Saxner 3 , A. Gustafsson 3 , A. 

Ahnesjö 3 

1 

MÄLAR HOSPITAL, Department of Medical Physics and Bioengineering, 

Eskilstuna, Sweden 

2 

STOCKHOLM UNIVERSITY AND KAROLINSKA INSTITUTET, Department of 


3 

NUCLETRON SCANDINAVIA, Uppsala, Sweden 

Purpose: One of the most used irradiation techniques in modern radiation 

therapy is step-and-shoot IMRT. The accuracy of this technique in delivering 

complex dose distributions depends strongly on the size of the subfields used 

to shape optimal conformality of the dose distribution. An aim of this study 

is to determine the minimum size of subfields that can be used practically in 

step-and-shoot IMRT, as well as to set recommendations for their use and 

validation. 

Materials: Two different detectors, a CC04 ion chamber and a SFD stereotactic 

diode, have been used for measuring head scatter factors in air (Sc), 

output factors (Scp) and dose profiles in water for a wide range of field sizes. 

The measurements were then compared to calculations done using a prerelease 

version of the Nucletron MasterPlan TM v 3.1 treatment planning system 

employing a novel, high resolution fluence modelling together with both 

the pencil beam and the collapsed cone algorithms. Collimator settings were 

independently determined from FWHM film measurements under a tungsten 

sheet close to the treatment head, in order to reduce perturbations from lateral 

electron transport and geometrical penumbra. An analysis of the influence 

and sensitivity of the results for small fields with respect to the linear 

accelerator source size and shape was also made. 

Results: The results showed good agreement between the measurements 

performed with the ionization chamber and the stereotactic diode and the 

calculations for field sizes larger than 2 cm 2 . For smaller field sizes, measurements 

with different detectors yield different results. Calculations show 

agreements with measurements with the smallest detector, given careful field 

size calibration and commissioning of calculation parameters. An analysis 

showed that uncertainties in collimator settings and source characteristics 

gave large uncertainties in Scp for such small fields. 

Conclusions: Clinically relevant small subfields for IMRT are handled in a 

proper way by the treatment planning system. However, fields smaller than 2 

cm 2 are very sensitive to uncertainties in source size, as well as calibration 

and reproducibility of the collimator settings. Therefore if subfields smaller 

than 2 cm 2 are to be used in IMRT extra care should be taken to determine 

the source characteristics and to calibrate the collimators. The volume of 

the detectors used for validation of such small fields and the loss of charged 

particle equilibrium conditions also have to be taken into consideration. 

1273 poster 

COMMISSIONING OF AAA AND PB ALGORITHMS (ECLIPSE 

V.8.05) BY MEANS OF THE MC CODE PENELOPE. STUDY IN THE 

BUILD-UP REGION FOR TANGENTIAL BEAM TREATMENTS. 

V. Panettieri 1 , R. Palanco-Zamora 1 , E. Wåhlin 1 , M. Westermark 1 , I. Lax 1 

1 KAROLINSKA INSTITUTET AND KAROLINSKA UNIVERSITY HOSPITAL, 

Hospital Physics, Stockholm, Sweden 

Purpose: In treatments with tangential beams, such as breast or head and 

neck cancer, accurate dose calculation in the build-up region is of major importance 

especially considering late skin toxicity. In most treatment planning 

systems (TPSs) dose calculation in this region is based on measurements in 

a flat water phantom. Thus for beams with oblique incidence and in presence 

of curved surfaces this dose calculation is usually performed in a very approximate 

way. In the frame of TPS commissioning discrepancies in the build-up 

region obtained by comparing the AAA and the PB algorithms implemented 

in the Eclipse TPS (v.8.05) with Monte Carlo (MC) simulations (PENELOPE 

and the penEasy package) were quantified. To take into account the effect 

produced by the incidence angle of the beam on the surface, calculations 

were performed for different beam angles. 

Materials: A semi-spherical water phantom was modelled representing the 

breast and/or the head and neck contour of a patient. This phantom was 

introduced both in the TPS and in MC simulations. To reproduce tangential 

beams, calculations were performed for 6 and 18 MV beams produced by a 

Varian Clinac accelerator for different angles of incidence respectively 15, 30, 

45 and 75 degrees and different field sizes 3x3, 10x10 and 40x40 cm2. In 

all cases depth doses were obtained in the beam central axis and compared 

with those obtained with MC calculations, in which detailed accelerator geometry 

was modelled to obtain realistic phase-space files. To validate MC data 

a comparison with plane parallel chamber measurements was performed.A 

breast patient case was also studied. Dose distributions obtained with the 

TPS were compared with those obtained from CT data using the MC voxelized 

version of penEasy. 

Results: In comparison to MC in the build-up region PB underestimates 

doses in a range between 1 and 3 mm at the 80-90% dose level depend- 

S 405 

ing on the field size for both 6 and 18 MV beams. Differences are lower for 

larger angles of incidence. With AAA instead the difference is up to 0.7 mm 

in the worst case (small field and high angle of incidence). 

Conclusions: The introduction of the AAA in clinical routine might considerably 

affect dose distribution in the build-up region compared to PB and differences 

have to be accounted for in treatment planning. 

1274 poster 

CORRECTION OF THE TREATMENT TABLE ABSORPTION IN 

IMRT: TABLE MODELS IN TPS AND MEASUREMENTS USING AN 

ELECTRONIC 3D DETECTOR 

G. Lutters 1 , M. A. Anne Marie 1 , E. Fujak 1 , P. Egli 1 

1 KANTONSSPITAL AARAU AG, Institut fuer Radio-Onkologie, Aarau, 

Switzerland 

Purpose: Delta4 is a 3D real time detector, manufactured by Scandidos, for 

verifying patient dosimetry in IMRT. Investigations were performed on Delta4 

to characterize the IMRT verification when the absorption by the treatment 

table is taken into account. Treatment table models have be developed to 

calculate the absorption of dose for the patient treatment and the verification 

phantom. 

Materials: The device consists of two orthogonal crossing diode detector 

planes mounted in a cylindrical PMMA phantom. The 3D dose dependence 

of the system was evaluated when treating trough the carbon table top. Simple 

11x11cm fields for different gantry angles were planned using Pinnacle3 

v7.6c treatment planning system with two different models of the treatment 

table. A simple model contracts all material into one layer. The CT-model 

consists out of the simplified real geometry with a chosen density .The dose 

distribution calculated by the treatment planning was compared to the dose 

measured with Delta4. 

Results: An angular dependence of +/-2.7% could be attributed to the carbon 

treatment tabletop (Siemens TXT). The CT-model could not correctly be 

calculated by the TPS. The simple model predicts correctly absorption and 

fluence changes. For the simple model all fields gave a gamma index (3mm / 

3%)


equation 5" which gives us a qualitative global view of the calculation carried 

out. 

1276 poster 

DOSE CALCULATION ALGORITHMS FOR HDR COLORECTAL 

CANCER BRACHYTHERAPY TREATMENT WITH A SHIELDED 

APPLICATOR 

X. Yan 1 , E. Poon 1 , B. Reniers 1 , T. Vuong 2 , F. Verhaegen 1 

1 MCGILL UNIVESITY, Medical Physics Unit, Montreal, Canada 

2 MONTREAL GENERAL HOSPITAL, Radiation Oncology Department, 

Montreal, Canada 

Purpose: Forty-two colorectal cancer patients were treated with 192Ir HDR 

brachytherapy. A shielding rod was employed to limit the dose to healthy tissue. 

The treatment plans were produced, however, without the shielding. To 

study the dose distributions in shielded cases three techniques were developed 

and compared. 

Materials: The PLATO shielding algorithm used a modified shielding algorithm 

which is part of the Nucletron PLATO HDR treatment planning system. 

A ray-tracing technique was developed to take the shielding attenuation into 

account without detailed modeling of scatter. The third and most accurate 

technique was a Dose kernel superposition algorithm, based on Monte Carlo 

simulations. Dose matrices around the 192Ir source for a unit time at different 

dwell positions in a shielded applicator were pre-calculated using a Monte 

Carlo code. 

Results: The figure shows the isodoses resulting from the three shielding algorithms 

for a patient. The 3rd algorithm produces the more realistic isodose 

lines. Although the dose to healthy tissue was reduced by 28% and 14% in 

terms of ’V90 to healthy tissue’ and ’D20 to healthy tissue’, for 10 out of the 

42 patients the volume covered by the 100% isodose lines was reduced by 

more than 5%. This cold spot issue is visible in the figure as the red tumor 

volume that was not covered by the pink 100% isodose line. This cold spot 

was caused by the shielding of the tumor by the shielding rod, which was not 

taken into account in the planning, and by the sometimes very uneven dwell 

time distributions produced by the PLATO planning system. The isodose lines 

resulting from the 1st algorithm are similar to that from the 3rd algorithm but 

exhibited unexpected zigzag patterns (top-left figure). The results quite accurately 

predict the dose to tumor volume with 1.2%±1.3% and 2.7%±2.9% 

differences in terms of ’target V100’ and ’target D90’ compared to the results 

from 3rd algorithm, but noticeably over-estimated the dose to healthy tissue 

up to 16% in terms of ’V90 to tissue’.The isodose lines resulting from the 

2nd algorithm generally agree well with the results from the 3rd algorithm, 

with -0.5%±0.8%, -1.6%±2.0%, 0.2%±3.3% differences in terms of ’target 

V100’, ’target D90’, ’tissue V90’, respectively. 

Conclusions: Use of any of the three shielding algorithms results in improved 

dose estimates to healthy tissue and the tumor. The tumor cold spots can 

be avoided by implementing a shielding algorithm at the treatment planning 

stage. The 3rd algorithm, which is the more accurate, was found to also be 

the fastest. 

1277 poster 

DOSE CALCULATIONS OF FIVE RU-106 EYE PLAQUE 

BRACHYTHERAPY WITH MCNP4C CODE 

R. Jaberi 1 , Z. Azma 2 , A. Mahmood Reza 2 , Z. Mohammad Hosein 3 

1 

INSTITUTE OF CANCER, Department of Radiotherapy, Tehran, Iran Islamic 

Republic of 

2 

SHAHID BEHESHTI UNIVERSITY, Department of Radiation Medicine, 


3 

NOVIN MEDICAL RADIATION INSTITUTE, Tehran, Iran Islamic Republic of 

Purpose: One of the treatments for intra ocular tumors is Brachytherapy with 

eye plaque RU-106. Assurance about the exact dose distribution is crucial for 

the clinical decision and the outcome of treatment. As the plaque shape and 

convexity also size, the dosimetry of the emitted β rays is particularly difficult. 

So the plaque simulations were performed by Monte Carlo N-Particle code 

(MCNP) and the dose distribution data in depth and surface of each layer 

was evaluated. Primer articles were done about CCA, CCB round plaques. 

Materials: Simulations of CIA, CCB, CCA, COB, CGD plaques were performed 

with MCNP4C code in water phantom. Geometry and materials were 

simulated in detail in spherical coordinate. The energy distribution of Rh-106 

was selected from JANIS history. 

Results: Dose rate, relative dose rate data (along the central axis of the 

applicators), dose profiles were evaluated from applicator surface up to 11 

mm. The results were in good agreement with manufacturer data. 

Conclusions: This study is comprehensive examination of different type of 

eye plaques for treatment of choroidal, ciliary body and Iris melanoma and 

accurate calculations of 3 dimensional dose distributions of eye plaques were 

done. 

1278 poster 

DOSIMETRIC ASSESSMENT OF NSCLC PATIENTS PLANNED FOR 

ACCELERATED HYPOFRACTIONATED BR25 PROTOCOL BASED 

ON MONTE CARLO SIMULATIONS 

V. Moiseenko 1 , I. Popescu 1 , M. Liu 2 , A. Bergman 1 , B. Gill 1 , S. Kristensen 

3 , T. Teke 1 

1 


Medical Physics, Vancouver, Canada 

2 

FRASER VALLEY CENTRE, BRITISH COLUMBIA CANCER AGENCY, 

Radiation Oncology, Surrey, Canada 

3 

FRASER VALLEY CENTRE, BRITISH COLUMBIA CANCER AGENCY, 

Radiation Therapy, Surrey, Canada 

Purpose: To quantify the accuracy of dose distributions produced according 

to the accelerated hypofractionated radiation therapy protocol BR25 using 

Monte Carlo (MC). To quantify differences between dose-to-medium and 

dose-to-water in MC as calculated for these NSCLC patients. 

Materials: Twelve NSCLC patients were selected as being eligible for BR25 

(11 retrospectively, and 1 enrolled). Largest GTV dimensions ranged from 2.9 

to 5 cm and GTV volumes from 5 to 33 cc. For each patient three plans were 

produced in Eclipse TPS. Plan 1 followed the BR25 protocol, i.e., planned 

with no inhomogeneity corrections. Plan 2 was identical to plan 1 except


that inhomogeneity corrections were enabled (as a QA requirement for the 

RTOG 0618 protocol). Plan 3 was independently planned with inhomogeneity 

corrections enabled. MC simulations for plans 2 and 3 were performed. MC 

doses were reported as both dose-to-medium and dose-to-water. Doses to 

target volumes and normal lung, defined as both lungs minus gross tumour 

volume were compared. Equivalent uniform dose (EUD) was calculated for 

PTV, and normal lung. V20 was calculated for normal lung. 

Results: MC results showed underdosing of PTV for all patients. Eclipse 

TPS plans (Plan 1 and Plan 3) were designed to cover 100% of the PTV with 

95% of the prescription dose (60 Gy). MC simulations of these plans showed 

that typically less than 90% of the PTV was covered with this dose. This 

underdosing was worse for plans created with inhomogeneities on (Plan 3), 

than for those following the BR25 guidelines (Plan 1). For a representative 

patient, PTV EUD were 60.0 Gy, 61.4 Gy and 58.8 Gy for no-inhomgeneity 

(Plan 1), inhomogeneity on (Plan 2), and MC respectively. Corresponding 

DVH are shown in the figure. Plan 3 PTV EUD’s were 60.8 Gy and 58.6 Gy 

for inohomogeneity on, and MC respectively. Differences seen in EUD for 

MC dose-to-water vs. dose-to-medium were small compared to those seen 

between Eclipse TPS, and MC-based calculations. 

Conclusions: The MC results suggest that Eclipse TPS based calculations 

overestimate the dose coverage of PTV in BR25 eligible patients. The requirement 

that planning be performed without the use of inhomogeneity correction 

is supported, but the re-calculation of these plans with inhomogeneity 

correction on tends to report an increase in PTV EUD, while MC calculations 

show a marked decrease. Our results imply that MC-based dose calculation 

should be used as a QA tool for lung SBRT. 

1279 poster 

DOSIMETRIC DIFFERENCES BETWEEN TG-43 AND MONTE 

CARLO CALCULATION FOR BREAST LDR BRACHYTHERAPY 

C. Furstoss 1 , M. J. Bertrand 1 , E. Poon 1 , B. Reniers 2 , J. F. Carrier 3 , J. P. 

Pignol 4 , J. Williamson 5 , L. Beaulieu 6 , F. Verhaegen 2 

1 

MCGILL UNIVERSITY, Medical Physics Unit, Montreal, Canada 

2 

MONTREAL GENERAL HOSPITAL, Medical Physics Unit, Montreal, Canada 

3 

CENTRE HOSPITALIER DE UNIVERSITE DE MONTREAL, Medical Physics 

Unit, Montreal, Canada 

4 

SUNNYBROOK HEALTH SCIENCES CENTRE, Departments of Radiation 

Oncology Medical Biophysics , Toronto, Canada 

5 

VIRGINIA COMMONWEALTH UNIVERSITY, Department of Radiation 

Oncology, Richmond, VA, USA 

6 

CENTRE DE RECHERCHE DE HOTEL DIEU QUEBEC, Quebec, Canada 

Purpose: To study the Monte Carlo (MC) codes PTRAN_CT and MCNPX2.5 

and compare the dosimetry results with the TG-43 formalism for a permanent 

seed implant for breast brachytherapy. 

Materials: The geometry validation of a model 6711 iodine seed was studied 

calculating the radial dose function in water. In order to develop a future fast 

MC treatment planning system, the calculation time between MCNPX and 

PTRAN_CT was analyzed calculating the figure of merit for water phantoms 

with different voxel number. The MC absolute dose in water was validated 

comparing with values calculated with the TG-43 formalism. In a breast phantom, 

dose measurements with TLDs and Gafchromic film were compared to 

MC calculations. The MC results of a treatment plan for a permanent seed 

implant of a breast cancer case were compared with TG-43 calculations calculating 

the dosimetric indices D90 and D50 from the DVH of the PTV. 

Results: The discrepancy between the calculated and published radial dose 

functions in water is less than 3% for the two MC codes. The calculation 

time comparison between MCNPX and PTRAN_CT shows that PTRAN_CT 

is 10%-30% faster than MCNPX for a voxel number between 200,000 and 

500,000. Good agreement is obtained for the absolute dose calculated by 

the two MC codes compared to the TG-43 calculation in water. The average 

S 407 

difference between absolute doses with TLDs and calculated MC is -0.15 % 

with 12.2 % maximum difference. The agreement between measured and calculated 

absolute isodoses in the EBT Gafchromic film is good, except close 

to the seed due to the important dose gradient (figure 1). The breast cancer 

patient plan shows that not taking the attenuation between the different 

seeds into account introduces a 2.3% difference on the dosimetric indices (interseed 

attenuation). Considering the patient composition equivalent to water 

introduces an 8.2% difference. 

Conclusions: This study shows that MCNPX and PTRAN_CT give good 

agreement in absolute dose calculations compared to TG-43 and experiments. 

Moreover, the patient dosimetry study reveals the interest to use a 

MC code to investigate tissue composition and interseed attenuation effects. 

PTRAN_CT seems to be somewhat faster than MCNPX for clinical application. 

1280 poster 

DOSIMETRIC EFFECTS OF THE CLINICAL IMPLEMENTATION OF 

THE ANISOTROPIC ANALYTICAL ALGORITHM IN STAGE III LUNG 

CANCER 

P. Koken 1 , J. Cuijpers 1 

1 VU UNIVERSITY MEDICAL CENTRE, Radiotherapy, Amsterdam, Nether- 

lands 

Purpose: To compare dosimetric planning parameters between Anisotropic 

Analytical Algorithm (AAA) and Pencil Beam (PB) calculations for stage III 

lung cancer treatments. 

Materials: 11 lung treatment plans calculated with Varian’s PB algorithm 

were retrospectively re-calculated with AAA and fixed monitor units (MUs). 

Both 6MV and 15MV beams were used. Tumour locations within the lung 

were equally distributed. Dosimetric parameters of the PTV were the minimum 

dose received by 95% and 99% of the volume (D95 and D99), the 

volume receiving 95% of dose or more (V95), and maximum and mean dose. 

Also parameters relevant for organs at risk were compared: the volume of 

normal lung tissue receiving 20 Gy and 5 Gy or more (V20 and V5), mean 

lung dose (MLD) and maximum spinal cord dose (MSCD). Mean PTV dose, 

D95 and D99 have not been reported previously. All parameters were compared 

using a two-tailed paired t-test. The same parameters were also determined 

and compared in re-optimized treatment plans with AAA, i.e. with 

different MUs and accepting a D99 other than 95%. 

Results: Whereas PB calculations are known to overestimate D95, D99 and 

mean PTV dose, AAA calculations are expected to decrease these parameters 

significantly. Significant decreases in D95 (3.5%) and D99 (4.6%) were 

found. Mean PTV dose was on average 2.2% lower but differences up to 

4.8% were seen. The latter concerns patients with a considerable amount of 

irradiated lung tissue near to the normalisation point. MLD, MSCD and maximum 

PTV dose do not differ significantly between both algorithms. V20 and 

V5 calculated with AAA are significantly lower than the ones calculated with 

PB. As expected, the amount of MUs significantly increases if D95 or D99 and 

beam-setup are kept fixed in AAA calculations. MUs are comparable with PB 

calculations if the 90%-isodose instead of the 95%-isodose encompasses the 

PTV. 

Conclusions: As known from the literature AAA alters D95, D99, V20 dose 

values significantly. The averaged difference in V20 is only 1%, which is not 

clinically relevant. MLD, MSCD and maximum PTV dose values differ not 

significantly using AAA. This is confirmed in the literature. Newly studied 

parameters V5 and mean PTV dose values were found to alter significantly 

too. Differences in V5 could lead to adjustments in the treatment plan. Finally, 

PTV encompassed by the 90%-isodose is found to be a clinical acceptable 

compromise between improved AAA calculations in lung-tissue and clinical 

experience based on PB calculations.


1281 poster 

ELECTRON BEAMS COMMISSIONING AND VALIDATION OF MONTE 

CARLO CALCULATION MODULE IN ONCENTRA MASTERPLAN 

T. Ventura 1 , M. D. C. Lopes 1 , B. Costa Ferreira 2 , A. J. Neves 2 , M. Capela 

1 

1 



2 

I3N - UNIVERSIDADE DE AVEIRO, Fisica, Aveiro, Portugal 

Purpose: The purpose of the present work is to fully explore and validate 

electron dose calculations in the Monte Carlo (MC) module of Nucletron Oncentra 

MasterPlan (OMP). At the same time the accuracy of on-site tuning of 

electron energies between two twin machines (Oncor Avant-Garde, Siemens 

linear accelerators) is tested by cross-check comparisons. 

Materials: Dosimetry data for electron beams of 6, 9, 12, 15, 18 and 21 

MeV have been measured for a recently installed linear accelerator labelled 

Oncor1 (Oncor Avant-Garde, Siemens). After data processing and implementation, 

the MC calculation module of OMP v. 1.5 (Nucletron) treatment 

planning system was fully explored, tested and validated. Calculated percentdepth 

doses (PDD) and off-axis dose profiles at different depths have been 

compared with measured curves using the γ-function criteria and the Spanish 

protocol (2%, 2 mm or 4%, 3 mm depending on the curve type). Also 

point dose values have been calculated both for open electron applicators 

and frames (square, rectangular and circular apertures). Airgaps between the 

electron applicator and the phantom surface have also been tested. Finally, a 

phantom for testing heterogeneities has been designed and constructed. The 

accuracy of the on-site tuning of all beam energies for a second linac (Oncor2) 

was tested by cross-check comparisons between measurements for Oncor2 

and calculations in the TPS where the commissioning data of Oncor1 was 

used. 

Results: Regarding the whole set of measurements required by the electron 

beam modelling in MC module we can say that in general OMP version 1.5 

does comply with the established quality criteria whenever the dose points 

are below the practical range (< Rp) for each energy. Beyond Rp and for 

dose profiles, for the lowest electron nominal energy (6 MeV) and the largest 

field sizes (>20x20 cm2) we have in average around 15% of the comparison 

points out of criteria. This percentage lowers with increasing energy. 

The study on air-gaps between the electron applicator and the water surface 

showed that MC module in OMP models very well the air layers showing 

complete agreement with measured curves. Point dose comparisons both 

for open applicators and frames (square, rectangular and circular apertures) 

revealed a good energy matching of both linear accelerators (Oncor 1 and 

Oncor 2). The study on heterogeneities was also done. 50000 histories have 

been established for clinical routine as the corresponding calculation time is 

compatible to interactive planning. 

Conclusions: The Monte Carlo (MC) module of Nucletron Oncentra Master- 

Plan models the electron beams with good accuracy. The good agreement of 

the cross-check comparisons between the two twin machines (Oncor Avant- 

Garde, Siemens linear accelerators) is maintained by a daily quality control 

programme. This allows treatment planning to be performed for one of the 

two linacs and treatment delivery to be done in either Oncor 1 or Oncor 2. 

1282 poster 

EVALUATION OF ELECTRONIC EQUILIBRIUM CONDITIONS NEAR 

BRACHYTHERAPY SOURCES 

D. Granero 1 , J. Perez-Calatayud 1 , M. Rivard 2 , C. Melhus 2 , M. C. Pujades 

1 , F. Ballester 3 

1 


2 

TUFTS UNIVERSITY SCHOOL OF MEDICINE, Radiation Oncology, Boston, 

USA 

3 



Purpose: For high-energy photon-emitting brachytherapy sources such as 

60 Co, 137 Cs, 192 Ir, and 169 Yb, the main contribution of the systematic uncertainty 

in the dose distributions near the sources is understanding of electronic 

equilibrium and the contribution of b-rays due to radioactive disintegration. 

Thus, it is important to study these effects in detail to accurately depict dose 

distributions near these brachytherapy sources. This work studies the relative 

importance of b-ray contributions to total dose (b + γ + x-ray), and feasibility 

of using the approximation "collision kerma equals dose in electronic equilibrium 

conditions." 

Materials: Characteristics of kerma and dose distributions were studied for 

spherical 60 Co, 137 Cs, and 192 Ir sources with composition, encapsulation, and 

dimensions similar to those existing in the literature. Dose contribution of 

b-rays and γ+x-rays were individually examined using the GEANT4 Monte 

Carlo radiation transport code. 

Results: The comparison of kerma and dose rate distributions indicate ~20% 

electronic disequilibrium within 1 mm of sources, with 60 Co have the most 

pronounced effect. When examining the dose contribution of b-rays, 60 Co 

again had the most pronounced effect out to 5 mm beyond the capsule, with 

b-rays contributions for 192 Ir and 137 Cs 1.5 and 0.5 mm beyond the capsule, 

respectively. 

Conclusions: The dosimetric effect of b-rays for high-energy photon-emitting 

radionuclides and the influence of the electronic disequilibrium near of the 

sources were studied using Monte Carlo methods. For 60 Co and 137 Cs 

brachytherapy sources, electronic disequilibrium has an important role near 

the source. For 192 Ir the main perturbing dosimetric effect near the source is 

from b-ray contributions and not electronic disequilibrium. 

1283 poster 

EVALUATION OF METHODS OF INTERPOLATION-EXTRAPOLATION 

OF GL(R) AND F(R,) FOR HIGH-ENERGY BRACHYTHERAPY 

SOURCES 

M. D. C. Pujades 1 , D. Granero 1 , J. Perez-Calatayud 1 , M. Rivard 2 , C. 

Melhus 2 , F. Ballester 3 

1 LA FE UNIVERSITY HOSPITAL, Valencia, Spain 

2 TUFTS UNIVERSITY SCHOOL OF MEDICINE, Boston, USA 

3 UNIVERSITY OF VALENCIA, Burjassot, Spain 

Purpose: To determine dose distributions for brachytherapy sources at spatial 

locations not included in the radial dose function, gL(r), and anisotropy 

function, F(r,θ), table entries interpolation and/or extrapolations on these tables 

are required. The objectives of this study are: 1) check methods of interpolation/extrapolation 

that allow to obtain gL(r) and F(r,θ) from the reported 

data accurately; 2) check the minimum number of entries in gL(r) and F(r,θ) 

that allow to reproduce dose distributions with enough accuracy for both radial 

distance and angle. 

Materials: High-energy photon-emitting brachytherapy sources have been 

studied: (1) Co-60 source from BEBIG (model Co0.A86); (2) Cs-137 source 

(model CSM3). (3) Ir-192 source from BEBIG (model Ir2.A85-2); (4) hypothetical 

Yb-169 source. All sources have 3.5 mm active length except the 

Cs-137 source that has an equivalent active length of 1.8 cm. These sources 

mimic the clinically available ones. The mesh used for r has been the ones 

typically used in literature (in cm): 0.25, 0.5, 0.75, 1, 1.5, 2-8 (1 cm step) and 

10. In the case of F(r,θ) the angle entries close to the longitudinal source axis 

vary in the different studies from a minimum step of 1 up to 10. Therefore four 

different steps have been evaluated 1, 2, 5 and 10. Linear and linear-linear 

interpolation and extrapolation have been used to obtain the dose in a 0.05 

cm-1 grid. Extrapolations have been done for r > 10 cm until r = 20 cm. The 

results have been compared with the values obtained from the Monte Carlo 

calculations for the aforementioned sources with the same grid. 

Results: For gL(r), interpolation result differences are < 0.2% for all the 

sources compared to MC raw data. Extrapolation differences increases when 

energy decreases: 1%, 2%, 4%, 6% at 15 cm and 2%, 5%, 11%, 15% at 20 

cm for the Co-60, Cs-137, Ir-192 and Yb-169, respectively. For F(r,θ) for the 

four sources and four approximations, the agreement with MC is < 0.5% in all 

the radial range (up to 20 cm) for the case of 1 and 2 steps with the exception 

of Cs-137 where it was < 1.5% for θ < 15. At 5 step the Co-60 source is < 

0.5% , the Cs-137 source is < 1.5% for θ < 15, the Ir-192 source is < 0.5% 

and the Yb-169 source is < 2% for θ < 5. At 10 step the Co-60 source is < 

1.5% for θ < 5, the Cs-137 source is < 2% for θ < 10, the Ir-192 source is < 

1.5% for θ < 25 and the Yb-169 source is < 2% for θ < 10. 

Conclusions: For gL(r), the typical mesh in literature is adequate for the interpolations. 

Caution is needed with extrapolations to larger distances for some 

sources, although because of the inverse square law the dose rate is very 

low and clinically less relevant. For F(r,θ) close to longitudinal axis source, 

1-2 step is adequate for all studied sources. Linear and linear-linear interextrapolation 

are adequate for high energy brachytherapy sources in contrast 

with the low energy sources case. 

1284 poster 

EVALUATION OF THE DOSIMETRIC ACCURACY OF COUCH 

MODELING FOR RADIOTHERAPY TREATMENT PLANNING 

L. Tillikainen 1 , J. Kauppinen 1 , T. Torsti 1 , A. Van Esch 2 , D. Huyskens 2 

1 VARIAN MEDICAL SYSTEMS FINLAND OY, Helsinki, Finland 

2 7SIGMA, QA-team in Radiotherapy Physics, Tildonk, Belgium 

Purpose: To evaluate the usefulness and accuracy of couch modeling for 

radiotherapy treatment planning purposes. 

Materials: To model the treatment couch, a set of templates were implemented 

in a development version of Eclipse TM Integrated Treatment Planning 

System (Varian Medical Systems, Inc.). The modeled couch types include 

the Varian Exact R○Treatment Couch with different panels, and the Varian 

Exact R○IGRT Couch. The templates were created based on manufacturer 

drawings, and typically consisted of the couch top with panel surface and interior, 

and movable structural rails. A couch template contains a default HU 

value for each couch part. These HU values were determined from CBCT 

images of the treatment couch, and were in some cases empirically tuned to 

match the dosimetric measurements. After creating the couch from a template, 

user is able to move the different parts of the couch (separately or as 

a whole) with respect to the body. The structures can then be edited using 

standard contouring tools, and also the HU values can be modified. In AAA


dose calculation algorithm, the couch structures are modeled by including 

them in the internal electron density matrix used as the basis for the dose 

calculation. The accuracy of the dose calculation was evaluated with planar 

measurements for a set of static fields at different gantry angles. The measurements 

were performed using a 2D ion chamber array (Seven29, PTW 

Freiburg) located between solid water plates in the PTW Octavius phantom. 

Results: The measured absorption for the different flat couch panels varied 

from 2% to 4%, while the attenuation caused by the movable structural rails 

was in the range of 15-20 %. When including the different couch structures in 

the AAA dose calculation, agreement between measurement and calculation 

was mostly within 3%, 3mm of the local dose, for all couch setups and gantry 

angles. Slightly larger errors (~5%) were detected along the very edge of the 

rails. 

Conclusions: Including the attenuation of the couch into the dose calculation 

significantly increases the agreement between measured and calculated 

doses for posterior and posterior-oblique fields. In addition, the visualization 

of the couch structures on the planning CT makes it considerably easier for 

the planner to avoid treatment through the structural rails, should he/she wish 

to do so. There are also possible benefits for arc treatments with full gantry 

rotation, where the rails cannot be avoided. 

1285 poster 

EVALUATION ON PHANTOM AND PATIENT IMAGES OF A CT 

NUMBER CONVERSION METHOD USED IN A MONTE CARLO 

TREATMENT PLANNING SYSTEM (MCTPS) FOR ELECTRON 

BEAMS 

A. Isambert 1 , S. Morrow 2 , F. Husson 2 , D. Lefkopoulos 1 

1 INSTITUT GUSTAVE ROUSSY, Medical Physics, Villejuif, France 

2 DOSISOFT, Cachan, France 

Purpose: To perform MC dose calculations in a realistic patient geometry, 

data from CT scanner images are used as input to the MC code. The purpose 

of our study was (1) to evaluate a CT number (HU) conversion method (material 

and mass density assignments) used in the MCTPS ISOgray TM (Dosisoft), 

(2) to determine the boundary (HUb) between air and lung materials for material 

assignment in thorax images and (3) the dosimetric consequences of 

this boundary value for electron beam treatments. 

Materials: Material and mass density assignments were first quantitatively 

controlled on CT images of the CIRS 062 phantom (The Phantom Laboratory), 

and four phantoms made of solid water, bone and lung equivalent slabs. 

Then, the conversion method was qualitatively controlled on brain, head and 

neck, and pelvis images. Material assignment for thorax images was studied 

more thoroughly. First, 22 sets of thorax images were used to define the HUb 

value by analysing the histograms of the HU value distribution. Secondly, 

for 4 patients referred for a breast cancer radiotherapy, dose distributions of 

electron beam treatments of intramammary nodes (IMN) were calculated for 

2 boundary values. 

Results: On the CIRS 062 phantom images, the difference between known 

and measured mass densities was below 0.06 g/cm3 for all the inserts and 

the material assignment was satisfactory. On slab phantoms, mass densities 

and materials were incorrect in the vicinity of bone slabs because of artefacts 

due to the bone high density. On patient images, mass density and material 

matrices were in good agreement with the corresponding CT images. However, 

HU values can be modified if contrast product is injected, or because 

of CT artefacts in the vicinity of a hip prosthesis or dental fillings. Regarding 

material assignment for thorax images, the boundary between air and lung 

materials was found to be equal to -950. The IMN dose volume histograms 

were not sensitive to the HU boundary definition since the structure is above 

the lungs. 

Conclusions: Issues in density and material assignments were raised in 

this work, due the use of contrast product or to artefacts in CT images. Our 

work focused on material assignment on thorax images to define the correct 

boundary between air and lung materials. Dosimetric consequences of this 

boundary definition were low considering electron beams. This study will 

have to be done likewise for photon beams to determine specific dosimetric 

consequences. 

1286 poster 

HIGH-RESOLUTION 4D MONTE CARLO SIMULATIONS FOR TIME- 

DEPENDENT RADIATION SOURCES WITH GENERAL KINEMATICS 

I. Popescu 1 , J. Lobo 2 , E. Tsang 3 

1 

BRITISH COLUMBIA CANCER AGENCY, Medical Physics, Victoria, Canada 

2 

UNIVERSITY OF BRITISH COLUMBIA, Department of Physics and Astronomy, 

Vancouver BC, Canada 

3 

UNIVERSITY OF BRITISH COLUMBIA, Computer Science, Vancouver BC, 

Canada 

Purpose: Monte Carlo (MC) simulations of complex treatment techniques, 

such as the recently developed VMAT (or more traditional IMAT), tumor tracking, 

or CyberKnife require the capability to model time-dependent radiation 

sources with general kinematics, with respect to the patient. Such treatment 

S 409 

modalities are commonly represented as a superposition of several static 

simulations, often characterized by poor space and time resolution. A bruteforce 

MC modeling of VMAT or IMAT, for example, may require hundreds 

of simulations, involving the manipulation of hundreds of large phase space 

and 3ddose files that render such problems computationally prohibitive. We 

present a radically different approach that eliminates the intermediate phase 

spaces altogether. 

Materials: We have developed a new source for DOSXYZnrc (and the concept 

could be equally applied to VMC++), which allows for gantry and collimator 

rotation, couch rotation and translation in any direction, arbitrary isocentre 

motion with respect to the patient, variable MU rate, and intensity-modulation 

by particle transport through moving MLC. The codes that model the linac 

and the MLC are compiled as shared libraries, which are dynamically loaded 

at run time. 

Results: We present benchmarking results of simulations using the new 

source, compared with standard methods, and show MC dose distributions 

for the following treatment modalities or situations: linac-based VMAT and 

IMAT, stereotactic radiosurgery with multiple arcs and couch rotation, total 

body irradiation using a sweeping beam, dose to patient during cone-beam 

CT image acquisition, tomotherapy, and CyberKnife. Validation comparisons 

with other dose calculation systems or TLD measurements in anthropomorphic 

phantoms will be presented. 

Conclusions: We have developed a powerful, high-resolution, 4D Monte 

Carlo technique for applications in modern radiation therapy. Our results illustrate 

the rich spectrum of radiation treatment techniques, previously regarded 

as too complex for routine MC simulations, to which our method can be readily 

applied. 

1287 poster 

INCORPORATING CALCULUS UNCERTAINTY INTO A MONITOR 

UNIT VERIFICATION SOFTWARE FOR EXTERNAL RADIOTHERAPY 

A. Perez-Rozos 1 , I. Jerez Sainz 1 , M. Lobato Muñoz 1 , J. L. Carrasco 

Rodríguez 1 

1 HOSPITAL VIRGEN DE LA VICTORIA, Radiofísica y Protección Radiológica, 

Málaga, Spain 

Purpose: To incorporate calculus uncertainty into an independent monitor 

unit verification software for external radiotherapy. 

Materials: We have developed a software to perform an independent monitor 

unit verification using the geometrical data exported from computerized 

planning system (Philips Pinnacle v.7.4f), based on Excel and VBA macros. 

Two parallel algorithm, hand and Clarkson, are used. Taken into account 

the fields conditions, geometrical factors and dosimetric data, we have established 

an uncertainty matrix to the calculus algorithm, based in accepted 

commissioning criteria (Van Dyk; Spanish QA protocol for computerized treatment 

planning systems). This uncertainties could be estimated from comparisons 

between measured and calculated data in the commissioning process 

of the computerized treatment planning system. 

Results: The software shows the monitor unit verification and the predicted 

uncertainty, taking into account the beams conditions. Identify possible errors 

in the position of normalization and calculus points could be carried out (e.g. 

points near field edges or under blocks). Uncertainty assignements are about 

2% inside fields near central axis, 15% penumbra region, and 10% under 

blocks or MLC (percentage of dose in point). To calculate the uncertainty due 

to a beams array is necessary to estimate the covariance matrix between 

beams. 

Conclusions: Calculus uncertainty in the verification process is a step in 

our quality assurance program, that allows a rationale choice between similar 

treatment plans. 

1288 poster 

INFLUENCE OF THE TUMOR DIAMETER, THE LUNG DENSITY 

AND THE DOSE CALCULATION ALGORITHM IN LUNG CANCER 

TREATED WITH STEREOTACTIC BODY IRRADIATION 

F. Gassa 1 , M. Ayadi 1 , C. Ginestet 1 

1 LÉON BÉRARD ANTICANCER CENTER, Radiotherapy, Lyon, France 

Purpose: Stereotactic Body Radiation Therapy in lung cancer (SBRT) represents 

a major advance in radiation oncology. It has been shown that SBRT 

can provide high tumor local control by introducing heterogeneous dose distribution 

throughout the tumor volume with increasing dose to the center of 

the tumor and without increasing normal tissues toxicity. However treatment 

of very small lung tumors can lead to a specific dosimetric problem which is 

the electronic disequilibrium due to the inhomogeneous medium. The purpose 

of this study is: 1/ to simulate different spherical tumors in lung; 2/ to 

compare dose profiles and MUs with different algorithms; 3/ to illustrate dose 

coverage of the PTV with a clinical case. 

Materials: We simulated two different tumors of 1.6cm and 3.6cm of diameter 

in lung which electronic density varies between 0.25 and 0.1. We generated 

a PTV with asymetric margins (5mm in all directions except 8mm in the cranio 

caudal direction). Treatment planning was performed using twelve 6 MV pho-


ton beams aimed at the PTV using the Beam Modulator (Elekta). Beams 

were conformally shaped to the PTV with a margin varying from 0 to 4mm. 

This margin was used to obtain a dose gradient inside the PTV according 

to stereotactic method. Thanks to this study we define a strategy of treatment 

to keep the same peripheral isodose. The dose was prescribed at the 

center of the tumor and calculated with both Clarkson and Superposition algorithms 

(Xio, CMS). For each configuration, we reported the isodose which 

encompassed 99% and 95% of the PTV and the total MU (on all fields). We 

realized the same study on one patient treated in SBRT under diaphragmatic 

compression with the stereotactic body frame (SBF, Elekta). The patient had 

an infracentimetric tumor in the right upper lung (with emphysema i.e a lung 

density < 0.1). The total dose prescribed was 48 Gy in 4 fractions on the 70% 

isodose. We compared dose coverage of the PTV and the total MU calculated 

with both algorithms. 

Results: For the simulated tumor of 1.6cm of diameter, preliminary results 

showed variations of 17% on dose coverage for 99% of the PTV and 13% 

on the total MU between Superposition and Clarkson. By varying margins 

around the PTV from 0 to 4 mm, a variation of 16% was observed on the prescription 

isodose. For the clinical case, we found that the total MU calculated 

with Superpostion is up to 50.7% higher that MU calculated with Clarkson. 

Conclusions: This study highlights the importance of the algorithm used in 

the prescribed dose and the difficulty to cover the PTV for very small tumors 

in very low density media treated with SBRT. The method of variable margins 

of conformation allows us to prescribe always on the same isodose in order 

to have a robust clinical evaluation of SBRT. 

1289 poster 

LEEDS EXERCISE COMMISSIONING HDR ONCENTRA PROSTATE 

BRACHYTHERAPY 

C. Richardson 1 , P. Bowes 1 , B. Al-Qaisieh 1 

1 ST JAMES’S INSTITUTE OF ONCOLOGY, Department of Medical Physics 


Purpose: Set up and clinical commissioning of the Oncentra prostate (OCP) 

treatment planning system (TPS) for HDR prostate brachytherapy. 

Materials: Commissioning measurements were carried out on the OCP system 

for HDR Ir-192 treatment planning. The procedure includes a comprehensive 

dose calculation around a single and multiple source arrangement. 

The outcome was compared to TG 43, Monte Carlo calculations, and the 

Plato brachytherapy planning system. Isodose computation and dose volume 

histograms were also evaluated. Physical and virtual phantoms were used 

to assess contouring and growing algorithms. US image transfer, geometric 

verification and orientation were validated by using CIRS 45 QA phantom. 

Results: Point dose calculation by the OCP was within 1% difference compared 

to that of hand calculation of TG43 and direct comparison with the 

Plato planning system. Comparing the OCP with the Plato system, the DVH 

generated by line source algorithms was within 3.7%. Virtual phantom contouring 

and margin growing revealed a discrepancy of up to 2.6% compared 

to calculated volumes. The ability to reconstruct catheters using ultrasound 

images varies depending on the quality of the image. The discrepancy estimating 

the "free length" measured by the OCP system was between 0.01 to 

2.79% compared to hand measurements. Image capture and registration by 

the OCP system from the ultrasound machine were acceptable as tested by 

CIRS 45 QA phantom. 

Conclusions: This work has assessed the functionality and the performance 

of the Oncentra Prostate brachytherapy treatment planning system for treatment 

of prostate cancer through a series of commissioning tests. For the majority 

of tests, for example dosimetry, the OCP showed an acceptable result. 

Some features such as margin growing tools were less accurate for certain 

scenarios. This has to be taken into account according to its clinical relevance 

and demonstrates the importance of fully understanding the system used. 

1290 poster 

MONTE CARLO CALCULATION ON THE DOSE MODULATION 

EFFECT USING DYNAMIC MAGNETIC FIELDS IN PHOTON BEAMS 

M. J. Cho 1 , K. Hwan Kim 1 , Y. Kee Oh 2 , K. Chul Shin 3 , J. Kee Kim 4 , D. 

Hyeok Jeong 5 , J. Kee Kim 6 

1 

CHUNGNAM NATIONAL UNIVERSITY HOSPITAL / CANCER RESEARCH 

INSTITUTE, Radiation Oncology, Taejon, Korea Republic of 

2 

DONGSAN MEDICAL CENTER, Radiation Oncology, Taegu, Korea Republic 

of 

3 

DANKOOK UNIVERSITY HOSPITAL, Radiation Oncology, Cheonan Chungnam, 


4 

CHONBUK NATIONAL UNIVERSITY, Research Institute of Clinical Medicine, 

Jeonju, Korea Republic of 

5 

SCHOOL OF MEDICINE, WONKWANG UNIVERSITY, Radiation Oncology, 

Iksan, Korea Republic of 

6 

DONG-A UNIVERSITY HOSPITAL, Radiation Oncology, Busan, Korea 

Republic of 

Purpose: We performed Monte Carlo calculations to verify dose modulation 

by dynamic magnetic fields in phantom. 

Materials: This study shows the uniform dose distributions at a depth region 

as a target on the central axis of photon beam by moving transverse magnetic 

field. Using step-by-step shift and time factor of the position of the electromagnet 

as an approximation of continuous moving, we have shown the depth 

dose curves for two cases of moving magnetic field along a depth line, constant 

speed and optimal speed. The optimal time factors were calculated by 

least square methods using depth dose data for static magnetic field. 

Results: Applying 3 T magnetic fields at center, the amount of dose enhancement 

was about 10 % in comparison to without magnetic field. 

Conclusions: We have verified that the flat depth dose is produced by varying 

the speed of magnetic field as a function of position as a result of Monte 

Carlo calculations. 

1291 poster 

MONTE CARLO ESTIMATION OF TOTAL SCATTER FACTORS OF 

SMALL PHOTON BEAMS USED IN IMRT 

S. Cora 1 , P. Francescon 1 , C. Cavedon 1 , P. Scalchi 1 , V. Santangelo 1 

1 OSPEDALE "SAN BORTOLO", Medical Physics , Vicenza, Italy 

Purpose: To calculate total scatter factors (sc,p) of small beams from a 

Siemens Primus linear accelerator used in Intensity Modulated Radiation 

Therapy (IMRT). 

Materials: A method is proposed to estimate sc,p of two square fields of 

0.3 cm and 0.5 cm size, which consists of Monte Carlo simulation with the 

Cavity code (EGSnrc-based) of the active volume of the detectors and of 

the treatment head (BEAMnrc). Different values of the FWHM (Full Width at 

Half Maximum) of the electron beam incident on the target have been used 

in the simulation of the treatment head (1.0 to 2.5 mm). The energy of the 

source was 7.0 MeV. The average dose calculated in the sensitive volume of 

the detectors was compared with experimental measurements, which were 

made with a PTW 31014 Pin Point chamber and 3 diodes (PTW 60012, PTW 

60008 and SunNuclear EdgeDetectorTM). The method is able to calculate 

the correction factors to be applied to experimental sc,p and also to provide 

the best estimate of the FWHM. 

Results: With the Pin Point chamber the corrected sc,p values of the two 

fields were 0.085 and 0.243 compared to 0.049 and 0.234 obtained with raw 

measurements. With the 3 diodes the average corrected sc,p were 0.075 and 

0.256 compared to 0.082 and 0.272, for the two fields. The estimated FWHM 

was between 1.8 and 2.0 mm for all the detectors. 

Conclusions: The advantages of the proposed method are: tuning of the 

electron beam incident on the target in the Monte Carlo model is not based on 

measurements of profiles and depth doses, which for small beams is dependent 

on the spatial resolution and energy response of the detectors. Instead, 

the modeling of the source in Monte Carlo was performed taking into account 

the whole range of possible values of FWHM and comparing the simulated 

and measured values of sc,p together with the "true" Monte Carlo value of 

the dose in a small volume of water. Moreover, the detectors were accurately 

simulated with their actual shape and chemical composition, which is very 

important for the effects of scatter and attenuation from the materials around 

the sensitive volume. Results were consistent with underestimation of the 

sc,p from the ion chamber, partly due to volume effect, and overestimation 

from the diodes due to non-water equivalent materials of the silicon substrate 

(for all the diodes) and of the metal shield (PTW 60008 and Sun Nuclear). 

The proposed method will be extended to other linear accelerators.

1292 poster 


MONTE CARLO SIMULATION OF ACCELERATOR ROOM SHIELD- 

ING 

N. Tarnavski 1 



Purpose: This work is dedicated to the analysis of a medical accelerator 

room shielding. It uses Monte Carlo technique in order to verify accelerator 

room shielding estimations made by conventional methods. Geant4 Monte 

Carlo package is used to simulate both electromagnetic and hadronic interactions 

between elementary particles, thus taking neutron scattering into account. 

The medical linear accelerator in question has been recently installed 

at Nved hospital (Denmark). 

Materials: Geant4 Monte Carlo package is used to define the medical linac 

head geometry and geometry of the treatment room. A predefined physics 

list is used, which includes both electromagnetic and hadron interactions, thus 

taking neutron scattering at higher energies into account. 

Results: Accelerator room shielding is estimated to give medical personnel 

no more than 0,1 mSv / year which is 10 times smaller than the allowed dose. 

Conclusions: Medical accelerator room shielding satisfies the demands imposed 

on it (being somewhat overprotected). 

1293 poster 

MONTE CARLO STUDY OF THE OUT-OF-FIELD SPECTRA FOR 6MV 

AND 15MV PHOTON BEAMS WITH AND WITHOUT MLC. 

K. Theodorou 1 , I. Paramerits 1 , P. Tsiamas 2 , C. Kappas 1 


2 UNIVERSITY OF THESSALY, Medical Physics Department, Larissa, Greece 

Purpose: The aim of this study was to investigate the energy spectrum outside 

the field limits of therapeutic high energy photon beams. Monte Carlo 

simulations were used in order to determine the dose and to confirm or to try 

to re-estimate the Energy correction factors used in off-field in-vivo dosimetry. 

Materials: The ELEKTA-SL18 medical accelerator was simulated for 6MV 

and 15MV, using the EGSnrc code. The simulation includes the regular jaws 

and the MLC. The output of each simulation was a square scoring plane at 

the surface of a water phantom. The energy spectrum, the mean energy, 

the energy fluence and other parameters were studied for annular areas centred 

on the Z axis, and for 1cm2 rectangular areas centred on both X and Y 

axis. These regions were selected every 1cm inside and outside the reference 

(10x10)cm2 field of the primary beam for SSD of 100cm. 

Results: The spectra and all the aforementioned parameters were found to 

be in relation to the position (distance of the selected area’s center from the 

field’s center), and their comparison revealed differences, that exceeded the 

statistical error, between areas that had the same distance from the center 

but were located on different axes. These differences were more important for 

the lower energy (6MV), as the contribution from leakage radiation is relatively 

higher. For the areas positioned on the surface of a water phantom and for the 

corresponding areas at a depth of Dmax, the percentage of dose in respect 

to the dose on the center of the beam was calculated for both simulations 

and experimental TLD measurements. Their comparison served to study the 

influence of the spectral differences on the measurements of this energydependent 

dosimetric system outside the treatment field. 

Conclusions: The ELEKTA SL-18 LINAC was simulated for photon beams 

of 6MV and 15MV with and without MLCs. The photon energies and the 

dose to the out-field areas close to treatment field are considerable and this 

should be taken into account when radiosensitive organs are close to the field 

limits. This could be more important to complicated IMRT treatments where 

the treatment time is altered. 

1294 poster 

PERIPHERAL DOSE ESTIMATION FOR 6 AND 18 MV RADIATION 

THERAPY PHOTON BEAMS: A COMPUTERISED METHOD BASED 

ON AN EXPERIMENTAL STUDY 

F. Zacharopoulou 1 , M. Mazonakis 1 , C. Varveris 2 , J. Damilakis 1 

1 

HERAKLION UNIVERSITY HOSPITAL, Medical Physics, Heraklion, Crete, 

Greece 

2 

HERAKLION UNIVERSITY HOSPITAL, Radiotherapy, Heraklion, Crete, 

Greece 

Purpose: Estimation of the radiation dose, delivered to organs at risk outside 

the primary field (peripheral dose, PD) during radiotherapy, is critical in many 

clinical cases. The aim of this study is to develop an applicable computerised 

method for PD calculation. 

Materials: The proposed method of PD calculation is based on an inclusive 

experimental study. PD measurements were performed using a thimble ionization 

chamber embedded in a water phantom. Phantom exposures were 

generated by a linear accelerator (LINAC), producing 6 and 18 MV photon 

S 411 

beams, equipped with a multileaf collimator (MLC). The effect of the following 

treatment parameters: distance from the field edge, photon energy, field 

size, depth, collimator orientation, source-to-skin distance, off-axis distance, 

use of wedges and blocks, on the PD was examined. The PD dependence 

on the above parameters was mathematically expressed and a software program 

was built, utilising NI Labview 8 and Matlab 7.1. To verify this computerised 

method, PD measurements were performed using thermoluminescent 

dosimeters (TLDs) positioned on an anthropomorphic phantom, simulating 

the body dimensions of an average adult man. The same set of TLD measurements 

was also carried out on a different LINAC generating 6 MV X-rays. 

Results: In this software program, the inputs are the treatment parameters 

and its output is the PD at any point of interest. The developed program 

allows direct PD calculation for all possible treatment parameters employed in 

clinical practice. The mean difference between the TLD readings and the PD 

calculated values was 20% and 19% for 6 and 18 MV X-Rays, respectively. 

The corresponding difference using the different LINAC was 21%. 

Conclusions: The new computerised method allows PD calculation with adequate 

accuracy and applicability to other LINACs as well. 

1295 poster 

RADIOTHERAPY TREATMENT PLANNING BASED SOLELY ON 

MAGNETIC RESONANCE IMAGING 

M. Karlsson 1 , J. Jonsson 1 , T. Nyholm 1 , M. Karlsson 1 , B. Zackrisson 1 

1 UMEÅ UNIVERSITY, Dep of Radiation sciences, Umeå, Sweden 

Purpose: Radiotherapy treatment planning is today based on computer tomographic 

(CT) images, a modality that employs ionizing radiation to form a 

3D image of the patient. Since the image displays how the radiation interacts 

with the material, i.e. how much of the radiation that is attenuated, it is 

a very good base for dose calculation. The drawback of CT images is the 

poor soft tissue contrast, since the attenuation in soft tissue is fairly constant 

whether the radiation passes through muscle, fat, brain or a tumor. For this 

reason, magnetic resonance (MR) imaging has become more interesting for 

treatment planning since it has superior soft tissue contrast, making it possible 

to delineate tumors and other soft tissue organs with greater accuracy. 

The MR images does not offer the attenuation information provided in CT images, 

making it impossible to perform dose calculations. To get around this 

problem, different parts of the anatomy can be delineated and assigned mass 

density values, making dose calculations possible. Automatic segmentation 

tools have here a large potential. Also, the MR images have an inherent geometric 

distortion caused mainly by inhomogeneities in the magnetic fields. 

These can be corrected for by software, but the accuracy needed to be assessed 

before the clinical use of the method can be put into place. 

Materials: The geometric distortion was investigated by comparing CT images 

to MR images of the same patients and also by comparing different 

phantoms. To assess the dosimetric accuracy of the manually assigned densities, 

treatment plans were generated on normal CT images, CT images with 

assigned mass density and MR images with assigned mass density. 40 patients 

were investigated in 4 different anatomical regions. 

Results: The results show that the geometric distortion after the 3D software 

correction was very small and should not cause significant error to the treatment 

plans. For the CT images with manually assigned densities, the mean 

error in monitor units of the different anatomical regions was within ± 0.3 %, 

and no single patient exceeded 2.0 % error. MR images with assigned mass 

densities served as base for treatment planning in 20 patients with cancer in 

the thoracic or pelvic region. In the pelvic region, a total mean error in monitor 

units of -0.8 % was present and in the thoracic patients, the mean error was 

0.0 %. No single patient exceeded 2.5 % error. 

Conclusions: From a dosimetric standpoint, it is very feasible to base treatment 

plans on MR images. There is however some practical problems with 

MRI coils and patient immobilization devices that need to be addressed before 

this routine can be clinically implemented for all treatment regions. 

1296 poster 

SKIN SPARING DURING TOMOTHERAPY TREATMENT PLANNING: 

DETERMINATION OF THE SKIN DOSE BY MONTE CARLO CALCU- 

LATIONS AND MOSFET DOSIMETRY. 

A. Delor 1 , J. M. Denis 1 , N. de Patoul 1 , E. Sterpin 1 , S. Vynckier 1 

1 UCL, ST-LUC, Radiotherapy and Oncology, Brussels, Belgium 

Purpose: During treatment planning (TPS) with Tomotherapy the skin can be 

considered as an organ at risk (OAR) and therefore can be optimized. The 

goal is to determine to what extend doses to the skin can be reduced and 

to compare the calculated skin doses from the TPS with measured values 

using MOSFET dosimetry and Monte Carlo (MC) calculated values. As the 

Tomotherapy TPS is based on a Superposition/Convolution (S/C) model, MC 

calculations could indicate possible deviations with the TPS with respect to 

entrance dose. 

Materials: Different Tomotherapy treatment plans were created as well for 

a cylindrical phantom (Tomotherapy cheese phantom) as for the head and 

neck region of a Rando phantom. As for routine treatment planning the skin


was drawn as a 3mm thick region, adjacent to the inside of the external contour. 

Plans were optimized using the constraints on organs at risk including 

the skin as done in daily practice for head and neck treatment planning 

at the Tomotherapy unit. Moreover, treatment plans were also created ignoring 

the skin as an OAR. In order to confirm the calculated doses by the 

TPS, these phantoms were irradiated as per the plans and MOSFETs (Metal 

Oxide-Silicon Semiconductor Field Effect Transistor) were placed at several 

points on the surface of the phantoms.In a second step, all plans were recalculated 

using a MC model, TomoPen, as described by Sterpin et al (1). This 

MC model is based on the Penelope algorithm. 

Results: Comparison of the resulting DVH’s from the different treatment 

plans indicate that the dose to the skin can substantially be reduced by optimizing 

the dose to a 5mm zone adjacent to the external contour. These 

findings were confirmed as well by the MOSFET measurements as by the 

Monte Carlo. 

Conclusions: The dose to the skin for head and neck treatments by Tomotherapy 

is known to be high. It can substantially be reduced by taking the 

skin into account as an OAR. Moreover, MOSFET dosimetry is well adapted 

to determine skin dose and our Monte Carlo model confirms the reduction 

of the skin dose.(1): "Monte Carlo simulation of helical Tomotherapy with 

PENELOPE". E Sterpin, F Salvat, R Cravens, K Ruchala, G H Olivera and S 

Vynckier, Phys. Med. Biol. (submitted, third revision). 

1297 poster 

STUDY OF THE DOSIMETRIC ACCURACY OF COLLAPSED CONE 

CONVOLUTION SUPERPOSITION ALGORITHM VERSUS MONTE 

CARLO SIMULATIONS FOR SMALL LUNG VOLUMES 

O. Calvo 1 , A. Gutierrez 1 , S. Stathakis 1 , P. Rassiah-Szegedi 2 , N. 



2 UNIVERSITY OF UTAH, Physics, Utah, USA 

Purpose: To quantify the accuracy of a collapsed cone convolution superposition 

(CCCS) algorithm against Monte Carlo (MC) simulations for small 

lung lesions subject to electronic disequilibrium when very small segments 

are used during the IMRT optimization process. 

Materials: IMRT plans for eleven (n=11) lung patients were created using 

Pinnacle3 7.6 planning system (TPS). The lung lesions measured less than 

3 cm diameter and less than 27 cm3 and were treated in our institution with 

SBRT techniques. The optimized intensity maps for each plan were then 

used to calculate the dose distributions using the CCCS algorithm. For each 

patient, seven optimized plans were created, each with different minimum 

segment sizes selected. Minimum segment sizes varied from 0.25cm2 to 

6cm2. The linear accelerator was modeled using MC code EGSnrcBEAMnrc 

and verified against commissioned measured data. Intensity maps for 

each plan and the patient CT dataset from the TPS were exported to our 

MC software. All patients were planned using a 5-field IMRT plan (Millennium 

120-leaf MLC and Varian 2100C 6MV beam). Dose distributions were 

calculated and normalized so that the isocenter receives 45.0Gy. Isodose 

distributions, DVH, and ROI statistics were used for comparison between the 

two calculation methods. 

Results: Comparison of the DVHs from Pinnacle3 and MC show similar target 

coverage between CCCS algorithm and MC. The figure below shows orthogonal 

profiles of the calculated dose planes for the 0.25cm2 minimum segment 

plan for a selected patient. The maximum difference was observed in 

the case of the 2cm2 minimum segment size where the maximum dose predicted 

by Pinnacle3 differed by 5% from the Monte Carlo calculated value. 

Differences in the minimum, maximum and mean dose of the PTV were less 

than ±5% while doses to critical structures agreed within ±6% for all cases 

investigated. 

Conclusions: Good agreement exists in the dose distributions predicted by 

the CCCS algorithm and MC method. The CCCS algorithm can accurately 

predict doses to small lung tumors. 

1298 poster 

STUDY OF THE DOSIMETRIC AGREEMENT BETWEEN TWO 

LINACS OF THE SAME MODEL 

J. F. Calvo Ortega 1 , N. Ferreiros Vázquez 1 , L. Garrido Beltrán 2 , J. Casals 

Farran 1 

1 HOSPITAL QUIRÓN BARCELONA, Radiation Oncology, Barcelona, Spain 

2 FACULTY OF PHYSICS -UNIVERSITY OF BARCELONA, ECM, Barcelona, 

Spain 

Purpose: To assess the clinical agreement between two same model linacs 

when are configurated on a commercial treatment planning system (TPS). 

Materials: Two Varian 2100CD linacs (Varian Inc, Palo Alto, CA) were commissioned 

during the opening of a new radiation oncology department. Although 

these machines are of the same model, not exact dosimetric match 

could be reached during their acceptance procedure. A difference of 1.5% 

were noted for 35cmx35cm transversal profiles on the shoulders zones and 

probably due to a not identical flattening filter available on both machines; 

an agreement of less than 1% was found on the remaining acceptance tests 

provided by the manufacturer. Strictly speaking, linacs are not radiological 

paired, but we wondered about its "grade of matching" for a clinical purpose. 

For that, only the basic input data corresponding to one linac (said "CL1") 

were taken in order to perform the modelling of Pencil Beam algorithm on a 

Varian Eclipse TPS (v 8.0) for the case of photon beams (6 and 18 MV). Once 

the treatment units corresponding to each linac ("CL1" and "CL2") were created 

and configurated on Eclipse, an individual TPS commissioning of each 

one of them was made having in account its own experimental data. For 

that task, computed against measured dose distributions were compared for 

several clinical situations (including open and EDW fields) following the procedure 

given by the document TG-53. Histograms of deviations were registered 

for each linac for three categories: high dose-low gradient (region 1), high 

gradient (region 2) and low dose (region 3). A Kolmogorov-Smirnov test was 

applied in order to determine if the two histogram datasets differ significantly, 

i.e., whether there is a significant difference between the delivered treatments 

with both clinacs. 

Results: Kolmogorov-Smirnov test of the paired histograms on the different 

regions of interest (with a significance level of 5%) is shown on the below 

table. Maximum differences between the cumulative distributions, D, and P 

values were registred. Where P means the probability of observing the given 

sample result under the assumption that the null hypothesis (H0) is true. In 

this case, H0 means the two data sets has identical distribution.


Conclusions: We obtained not significant statistical difference between our 

two linacs when basic input data of one of them were used to configure both 

machines on Eclipse TPS. So, in our case, the radiological differences about 

1.5% found on the acceptance profiles don’t have a influence in order to consider 

our linacs as matched units. 

1299 poster 

SUPERFICIAL DOSE DISTRIBUTION IN BREAST FOR TANGENTIAL 

PHOTON BEAMS 

R. Chakarova 1 , A. Lindberg 2 , G. Bankvall 2 , M. Gustafsson 1 , A. Palm 1 , 

A. Bäck 1 

1 SAHLGRENSKA UNIVERSITY HOSPITAL, Department of Medical Physics 

and Engineering, Göteborg, Sweden 

2 SÖDRA ÄLVSBORG HOSPITAL, Engineering and physics, Borås, Sweden 

Purpose: It is well known that the calculation of the dose distribution close 

to breast/air interface is complicated due to lack of electron equilibrium and 

incomplete scatter conditions in this region. The objective of this study is to 

examine the superficial (0-2 cm) dose distribution in a breast shaped phantom 

irradiated by tangential photon beams. 

Materials: A 6 MV open 10x10 cm beam is tangentially incident on a 20 

cm diameter cylindrical solid water phantom. Measurements on an Elekta 

Precise and a Varian 600C accelerator are performed using square TLD rods 

(1x1x6 mm) and Gafchromic EBT film. Dose profiles from the surface towards 

the geometrical center of the phantom are obtained at three positions; beam 

axis entrance and exit, and laterally (perpendicular to the beam). Treatment 

planning calculations are performed for Elekta using MasterPlan 3.0 pencilbeam 

(PB) and collapsed-cone (CC) algorithms, and for Varian using Eclipse 

7.5.18 pencil-beam (PBC) and AAA algorithms. Monte Carlo calculations are 

carried out for both accelerators by implementing BEAMnrc models of the 

accelerator heads. Results for two opposed beams are derived by addition. 

Results: For one field, the entrance and exit dose at 0,5 mm depth are more 

than 45% lower than the lateral one, according to TLD measurements on 

Elekta. The dose variation is within 7% for the lateral profile beyond 2 mm 

and within 3% for the exit profile, compared to 30% difference at the beam 

entrance. The figure shows experimental and calculated lateral dose profiles 

for one field. The film measurements, normalized to the CC dose at 2 cm 

depth, agree well with the TLD results. It is seen that the PB algorithm overestimates 

the dose the first 3 mm from the surface, while the PBC algorithm 

underestimates the dose the first 10 mm. PB results are more consistent 

S 413 

with CC ones compared to PBC and AAA results. Measurements and Monte 

Carlo calculations support the CC and AAA algorithms 

Conclusions: When irradiated by two opposed tangential beams, the lateral 

superficial part of the breast receives full dose beyond 2 mm without added 

bolus material, whereas the build-up region is up to 8 mm where the beams 

enter. Eclipse PBC significantly underestimates the superficial dose at the 

beam entrance and transverse to the beam. MasterPlan PB overestimates 

the dose close to the lateral surface. CC and AAA calculations show good 

agreement with experimental and MC data. 

1300 poster 

TEST FIELDS FOR IMRT COMMISSIONING 

A. R. Figueira 1 , A. L. Carvalho 1 , M. Trindade 2 , V. Batel 1 

1 HOSPITAL DE S. JOAO, Radioterapia, Porto, Portugal 

2 CENTRO HOSPITALAR TRÁS-OS-MONTES ALTO DOURO, Radioterapia, Vila 

Real, Portugal 

Purpose: The dosimetric commissioning of an intensity modulated radiotherapy 

(IMRT) planning system should include the verification of progressively 

more complex fields. Several recommendations suggest starting with simple 

intensity patterns, like a wedge, a pyramid or a well. The purpose of this work 

was to create a set of simple test fields to check the dosimetric calculation 

accuracy during IMRT planning commissioning. 

Materials: A set of fields, with simple intensity patterns, were created to test 

the modelling of a 6 MV photon beam machine during the commissioning 

of CMS XiO treatment planning system (TPS) for step-and-shoot IMRT. The 

fields were created by editing the intensity levels, point by point, on a 10x10 

cm2 field and then allowing the TPS to do the necessary segmentation. The 

dose calculation results from the planning system were compared with measurements 

done on a Siemens Primus linear accelerator. For absolute point 

dosimetry we used an ion chamber and diode, and for 2D relative dose distribution 

comparison we used Gafchromic EBT films and a 2D ion chamber 

array (Scanditronix Wellhofer I’mRT MatriXX). Dose plane distributions were 

analysed and compared using both RIT113 v5.0 (Radiological Imaging Technology, 

Inc.) and OmniPro I’mRT (Scanditronix Wellhofer) software. 

Results: After the measured data we acquire for those fields, we could recalculate 

them on the TPS after each modelling parameter adjustment and 

repeat the comparison until we reached the desired result. We were able to 

identify and correct some penumbra and MLC transmission modelling problems.

S 414 PHYSICS AND TECHNOLOGY : OPTIMIZATION AND DOSE PLANNING 

Conclusions: The set of test fields allowed us to improve the commissioning 

process and to quantitatively check the TPS calculation accuracy for IMRT 

fields before clinical use. 

1301 poster 

THE PRECISION OF THE PENCIL BEAM ALGORITHM IN GATED 

RADIOTHERAPY OF BREAST CANCER 

D. E. Nygaard 1 , G. Persson 1 , T. Juhler-Nøttrup 2 , L. Aarup 1 , K. Kræmer 

1 , A. Pedersen 1 , L. Specht 1 , S. Korreman 1 

1 

THE FINSEN CENTER - RIGSHOSPITALET, Radiation Oncology, Copenhagen, 

Denmark 

2 

HERLEV HOSPITAL, Oncology, Herlev, Denmark 

Purpose: At Rigshospitalet left-sided lumpectomy patients with axillary 

lymph node metastases have since 2004 been offered supplementary gated 

radiotherapy during deep inspiration to minimize dose in heart and lungs. 

Dose plans have been calculated in Eclipse with the Single Pencil Beam algorithm 

(SPB), using the Modified Batho power law to correct for inhomogeneities. 

However, the fact that the Modified Batho power law does not take 

proper consideration of lateral electron scatter in e.g. tissue with low density 

has given rise to question the precision of the dose plans, since the lung 

density during deep inspiration is lower than the free breathing density. 

Materials: 8 left-sided lumpectomy patients were CT-scanned during deep 

inspiration breath hold (DIBH), end-inspiration gating (IG), free breathing (FB) 

and end-expiration gating (EG) respectively. 3 of the patients were also CTscanned 

during end-expiration breath hold (EBH). For each CT-scan, dose 

plans were calculated using SPB with basis in two tangential fields and an 

anterior field. Clinical target volume (CTV) included remaining breast, level III 

of the axillary lymph nodes plus periclavicular and parasternal lymph nodes, 

and total dose to CTV was 48 Gy. Dose in CTV, heart and left lung was 

examined with the Analytical Anisotropic Algorithm as reference. 

Results: In the CTV, the dose is estimated a little too homogenous by SPB, 

but the degree can be considered approximately independent of respiration 

phase. In the heart, the average dose Dm plus the volume that receives 5 and 

24 Gy or more respectively, i.e. V5Gy and V24Gy, are underestimated, and 

the absolute deviation increases slightly across the respiration phases from 

DIBH to EBH. In the left lung, Dm is underestimated, and the relative deviation 

is predominantly larger in the end-inspiration phase than in the end-expiration 

phase with average between 3.8 - 5.7 %. In the left lung, relative V5Gy and 

V24Gy are underestimated while relative V40Gy is overestimated, and the 

absolute as well as the relative deviation decreases typically from DIBH to 

EBH. The deviations are in general largest for V5Gy where the average deviations 

are between 17.4 - 26.6 % and 11.3 - 13.9 %-point respectively. 

Conclusions: With respect to the CTV and the heart, SPB can be considered 

unproblematic. Regarding the left lung, especially the underestimation 

of V5Gy must be considered as problematic - during deep inspiration as well 

as over the rest of the respiration cycle. 

1302 poster 

VALIDATION OF AN ANALYTICAL DOSE CALCULATION METHOD 

FOR 192IR HIGH DOSE RATE BRACHYTHERAPY APPLICATIONS 

E. Poon 1 , F. Verhaegen 1 

1 MCGILL UNIVERSITY, Medical Physics Unit, Montreal, Canada 

Purpose: We have developed an analytical dose calculation method to account 

for heterogeneities and patient dimensions for high dose rate (HDR) 

brachytherapy applications. Its validity at 192 Ir energies was examined. 

Materials: A dose kernel superposition and ray tracing approach that separates 

primary and scatter dose calculations was implemented in MATLAB. Using 

the PTRAN_CT Monte Carlo (MC) code, primary and scatter dose kernels 

of an HDR source in water were pre-calculated. To account for dose perturbations 

around high density structures, 3D kernels of the source in the presence 

of the applicator and shielding geometries were also used. Changes in 

photon attenuation and scatter dose due to anatomical heterogeneities were 

corrected for by ray tracing in the material and density matrices, both of which 

were derived from CT images. Dose to tissue-equivalent media was calculated 

using the effective mass energy absorption coefficient ratios based on 

the photon spectrum of an encapsulated source. For bony structures, the 

ratios are sensitive to the softening of the 192 Ir spectrum and therefore were 

parameterized as a function of distance in water. The smaller backscatter 

contribution near the skin was quantified by MC simulations of an 192 Ir point 

source at various positions in a 30 cm diameter water sphere. Scatter correction 

factors that depend on the distances between the source, the skin 

and the point of interest were obtained. Results of the analytical method 

and patient-specific PTRAN_CT simulations for several treatment sites were 

compared. 

Results: The proposed algorithm can accurately calculate dose in regions 

with tissue-equivalent densities, and near tungsten shielding for rectal treatment. 

It can also predict the reduced scatter dose near the skin for breast and 

head and neck cases. Compared to MC calculations, there are differences 

in the lung due to a smaller backscatter contribution. Some discrepancy is 

observed around large bony regions several centimeters away from the active 

dwell positions because the shift in the 192 Ir spectrum in the bone is not 

the same in water. This leads to uncertainties in the mass energy absorption 

coefficient ratios limited to at most a few percent. 

Conclusions: Our analytical method has been validated by MC calculations 

for HDR brachytherapy, including treatments with shielding when applicationspecific 

dose kernels are used. However, differences are expected near the 

lung or large bony structures. 

1303 poster 

VERIFICATION OF PHOTON DOSE CALCULATION ACCURACY BY 

THE PENCIL BEAM AND ANALYTICAL ANISOTROPIC ALGORITHM 

USING MOSFET DETECTORS 

A. Swinnen 1 , A. Nulens 1 , J. Verstraete 1 , F. Van den Heuvel 1 

1 UNIVERSITY HOSPITAL LEUVEN, Radiotherapy, Leuven, Belgium 

Purpose: The uncertainty of dose calculations should be below 3% to correlate 

treatment outcome with prescribed dose. Modern treatment planning 

systems (TPS) can fulfill this demand but due to approximations of the calculation 

algorithms larger errors in calculated dose can occur in and near 

to heterogeneities. The purpose of this study is to evaluate the accuracy 

of the dose calculated in and near heterogeneous media by the algorithms 

implemented in our commercial TPS: a pencil beam (PB) and an analytical 

anisotropic algorithm (AAA). 

Materials: Both algorithms are implemented in the Eclipse (Varian Medical 

Systems, Inc.) TPS for calculation of dose distributions for photon beams. 

Two phantom configurations, composed of layers of polystyrene and cork 

(3cm and 7cm cork respectively), are irradiated with 6MV, 10MV and 18MV 

open photon beams of field sizes varying between 3x3cm 2 and 10x10cm 2 

delivered by a Clinac 2100C/D. Absolute dose measurements are performed 

with the MOSFET detector positioned at the central axis at different depths 

in cork, at the interface cork-polystyrene and in polystyrene behind the lowdensity 

medium. The MOSFET detector is calibrated prior to the measurements 

and validated with ionization chamber measurements. 

Results: The repeatability of the calibration factor per detector in all beam 

energies is on average 0.6%. Two measurements per depth are in general 

reproducible within 1%. In the water equivalent part of the phantoms, the 

AAA and PB calculations agree with the measurements within 2%. Depth 

dose curves inside the cork are better with AAA than with PB, as PB generally 

overestimates the dose with 5%, while the agreement between AAA and 

measurements is on average 2.5%. For 18MV photon beams and field size 

3x3cm 2 , we observe that the difference between predicted depth doses by 

both algorithms inside the low-density medium is most pronounced and that 

both algorithms overestimate the dose. At the interface cork-polystyrene, the 

dose measurements agree more with AAA (within 2.5% on average) than with 

PB (within 8% on average). 

Conclusions: MOSFETs are found to be suitable for measuring doses in 

low-density media where there is a severe perturbation due to electronic disequilibrium. 

While the PB algorithm does not model the reduction in central 

axis dose in the low-density medium, the AAA does predict the dose reduction 

and re-buildup with sufficient accuracy. 

Physics and technology : Optimization 

and dose planning 

1304 poster 

A DOSIMETRIC COMPARISON OF IMRT VERSUS 3-D CONFOR- 

MAL BOOST FOLLOWING PELVIC RADIATION FOR HIGH RISK 


L. Tsvang 1 , R. Pfeffer 1 , Z. Symon 1 

1 THE CHAIM SHEBA MEDICAL CENTER, Oncology, Ramat Gan, Israel 

Purpose: The summed dosimetry of 4 field pelvic radiation and dose escalated 

3DCRT boost is associated with areas on inhomogeneity to critical 

organs adjacent to the CTV increasing the risk of toxicity. We hypothesized 

that an optimized IMRT boost which accounts for dose delivered to organs at 

risk during pelvic radiation would result in less inhomogeneity of dose and potentially 

reduce the risk of hot spots and toxicity. The purpose of this study is 

to compare IMRT to 3DCRT boost following pelvic radiotherapy with a special 

emphasis on the control of dose homogeneity to organs at risk. 

Materials: CT scans of 12 high risk prostate cancer patients treated with a 4 

field pelvic plan to 46 Gy followed by an IMRT boost to 36 Gy were utilized for 

this study. Patients were immobilized in the supine position with a knee rest. 

The CTV for the IMRT boost included the prostate and proximal SV expanded 

by 0.8 cm for PTV. In order to create a dose gradient within the PTV in the 

direction of adjacent critical organs which had previously received radiation in 

the pelvic plan, a smaller PTV (PTV82) comprising the prostate with a 0.6 cm

margin was generated Using Boolean operators the areas of PTV which overlap 

with rectum and bladder were defined as structures named PTV-Rectum 

and PTV-Bladder, respectively. Our 3DCRT boost protocol includes 2 plans: 

first the CTV is expanded by 1 cm (PTV1) and planned to 10 Gy and then 

expanded by 0.5 cm posteriorly towards the rectum and 1 cm in all other 

directions (PTV2) and planned to 26 Gy. The mean dose for each structure 

and specific DVH points for critical organs were normalized to the prescription 

dose for comparison. 

Results: IMRT boost decreased the mean dose to critical organs, particularly 

to the femur and permits control of the gradient dose to the PTV-Rectum and 

PTV-bladder. Table 1 shows an average value and range of mean dose for 

investigated structures and critical organs. 

Conclusions: We confirmed our hypothesis that IMRT boost using constraints 

which account for previous dose to critical structures achieves a more 

homogeneous dose to critical structures adjacent to the CTV potentially reducing 

toxicity. 

1305 poster 

A GEOMETRIC INDEX FOR BEAM ORIENTATION OPTIMIZATION IN 

LUNG CONFORMAL RADIOTHERAPY 

J. Meng 1 

1 NOVA SCOTIA CANCER CENTRE, CAPITAL DISTRICT HEALTH AUTHORITY, 

Radiation Oncology, Halifax, Canada 

Purpose: Beam orientation optimization has significant effect on lung conformal 

treatment planning. In comparison with other treatment sites such as 

prostate, the variation of tumour location, tumour volume and tumour shape of 

lung cancer is outstanding. Therefore, beam orientation optimization in conformal 

lung treatment deserves close attention. Manually optimizing beam 

orientation, however, is very time-consuming and extensive optimization is 

not practical. To facilitate treatment planning optimization for lung conformal 

radiotherapy, a geometric index was introduced. 

Materials: The geometric index for beam orientation optimization introduced 

in this paper is a function of gantry angle. This index is calculated based on 

patient’s anatomy only. No dose calculation is involved. In order to calculate 

this index, a computer software was created. Once a case is selected from a 

patient list, the software reads patient’s anatomy and calculates the geometric 

index. The gantry angle resolution is flexible to speed up the calculation 

with 0.5 degree near the optimal range. With a set of optimal gantry angles 

recommended by this geometric index, beam orientation optimization can be 

very quick. All radical lung patients at Nova Scotia Cancer Centre are treated 

by conformal two-phase technique with the summed dose of 60 - 63 Gy to 

PTV2. The normal tissue constrains for radical lung cases include the normal 

lung volume that receives 20 Gy and 10 Gy (V20 < 30% and V10 < 50%), 

maximum average dose to normal lung (20 Gy) and maximum point dose to 

spinal cord (50 Gy). To test this geometric index, conformal lung plans generated 

in the past two years are reviewed and seven most difficult cases are 

selected. Due to the large tumour volume (average 794 cm3 or 24% of normal 

lung volume) and small distance between tumour and spinal cord, the original 

two-phase plans did not satisfy one or two of the normal tissue constrains 

although the dosimetrists made a great effort to manually optimize beam orientation 

as well as beam aperture and beam weighting. These seven most 

difficult cases were re-planned by using this geometric index method. The 

new plans and original plans are compared according to V20, V10, Average 

lung dose and maximum cord dose. 

Results: By changing the gantry angles as recommended by the geometrical 

index, the new plans are significantly improved. All constrains are satisfied 

by the new plans. On average of the seven cases tested, V20 and V10 are 

reduced by 186 cGy and 360 cGy respectively. The average dose to normal 

lung reduced by 138 cGy. The maximum dose to spinal cord is also reduced 

by 82 cGy. 

Conclusions: The geometric index can be a useful tool for beam orientation 

optimization. 

PHYSICS AND TECHNOLOGY : OPTIMIZATION AND DOSE PLANNING 

1306 poster 

S 415 

ASSESSMENT OF THE SUITABILITY OF CT, MRI AND CT-MRI 

IMAGE FUSION FOR POST IMPLANT PROSTATE BRACHYTHER- 

APY DOSIMETRY ACCORDING TO THE ESTRO/EAU/EORTC 

RECOMMENDATIONS 

J. Bowden 1 , B. Al-Qaisieh 1 , A. McCabe 1 , G. Wright 1 , B. Carey 2 , P. 

Bownes 1 

1 ST JAMES’S INSTITUTE OF ONCOLOGY, Departments of Medical Physics 


2 ST JAMES’S INSTITUTE OF ONCOLOGY, Department of Radiology, Leeds, 


Purpose: To determine the dependence on the imaging modality used of the 

ESTRO/EAU/EORTC post implant prostate brachytherapy dosimetry parameters. 

Materials: Inter and intra-observer variability in prostate contouring and seed 

identification on CT and MRI was determined. Observer variability in contouring 

was determined by asking two observers to outline the prostate for 

6 patients a total of six times at weekly intervals on both CT and MR. The 

observers also independently identified seeds on 3 patients. Dose volume 

analysis was performed with calculation of the implant V100, V150 and V90. 

For the comparison of the dosimetry parameters as recommended by ES- 

TRO/EAU/EORTC, a total of 43 patients were used. On each CT and MRI 

scan the prostate, rectum, urethra and seeds were outlined once by the two 

observers. Dosimetry indices were reported for each set of scans individually. 

The CT images were fused with the MRI maintaining all the organ contours 

previously demarcated. Post implant dosimetry was performed using the contours 

from the MR scans and the seed positions identified on CT. 

Results: The average uncertainty in the outlining of the prostate was 30.2% 

and 23.4% for CT and MRI respectively. The apex was the site of highest uncertainty 

and the mid-section the lowest. There was no significant difference 

in the dosimetry indices calculated whether seeds were identified on CT or 

MRI. The average D90 values were 91.9% for MRI, 90.1% for CT and 84.1% 

for CT-MR with the difference between the CT-MR and CT and MR being significant. 

For the V100 the average values were 83.7% for the MRI, 83.7% 

for the CT and 80.8% for the CT-MR. The difference in V100 values was only 

significant for the CT-MR to CT. For the V150, the mean values were 53.5% 

for the MRI, 50.2% for the CT and 48.8% for the CT-MR with the difference 

only being significant between the CT-MR and MR. There was no significant 

difference between the CT V200 and that of the CT-MR but all other prostate 

parameters showed significant differences between the modalities. Overall, 

for the prostate and prostate margin contours, 10 different dose parameters 

have been calculated for CT, MR and CT-MR. Out of these 10 values, 9 were 

significantly different between CT and CT-MR whereas this was only 6 of the 

parameters between CT and CT-MR. For the rectal contour, there was a statistically 

significant difference between the CT-MR and both the CT and MR. 

For the urethra dose parameters, there was a statistically significant difference 

between the CT-MR and the CT values. 

Conclusions: This study shows that prostate contouring can be more accurately 

and reproducibly performed on MRI images than CT images but that 

the identification of implanted seeds is more accurately performed using CT 

images. The use of fused MR-CT images therefore represents the preferred 

method of choice for prostate post-implant dosimetry. If however CT-MR fusion 

is not available then CT alone is preferable over MR. 

1307 poster 

DMLC AND BEAM DOSE RATE BASED 4D RADIOTHERAPY 

L. Papiez 1 , R. Abolfath 1 

1 UNIVERITY OF TEXAS SOUTHWESTERN, Radiation Oncology, Dallas, USA 

Purpose: To introduce new method of delivery of DMLC IMRT therapy to 

moving body anatomy that differentiates dose to target and organs at risk. 

The shaping of intensity maps over moving target and healthy tissue is 

achieved through simultaneous control of leaf motions and beam dose rates. 

Materials: Formulas relating leaf speeds and beam dose rates for delivering 

planned intensity profiles to static and moving targets in DMLC IMRT are 

derived and tested for multiple intensity maps and multiple target motion patterns. 

The analysis of equations that define algorithms for DMLC IMRT delivery 

under variable beam dose rate reveals multitude of delivery strategies. 

A specific sub-class of strategies is distinguished that is suitable for clinical 

applications. This class of equivalent relative to moving target deliveries is 

notable for the condition of invariant motion of leaves provided they are defined 

as functions of cumulative number of monitor units and not as functions 

of time. This subclass of DMLC IMRT delivery strategies to moving body 

anatomy generalizes existing techniques of Varian DMLC IMRT irradiation 

methodology to static body anatomy. 

Results: We illustrate first how new algorithms work for DMLC IMRT deliveries 

to static targets. Then we show how newly derived algorithms deliver 

intensity maps to moving targets when variable beam dose rates are applied. 

In turn, we present an example of how new deliveries work in case when they 

are adapted in real time, when random motion of the target is registered at 

treatment . Finally, we show how variable beam dose rates can be used to


improve dose distributions in IMRT therapy to moving body anatomy relative 

to optimized dose distributions achievable with IMRT to static body anatomy. 

Conclusions: The DMLC IMRT utilizing variable beam dose rate allows improving 

radiation therapy to moving body anatomy relative to therapy for static 

body anatomy. 

1308 poster 

DOSIMETRIC COMPARISON OF PERMANENT PROSTATE 

BRACHYTHERAPY PLANS USING CS-131, I-125 AND PD-103 

SEEDS 

R. Yang 1 , J. Wang 1 

1 PEKING UNIVERSITY THIRD HOSPITAL, Department of Radiation Oncology, 

Beijing, China 

Purpose: To compare the dosimetric differences of permanent prostate 

brachytherapy utilizing Cs-131, I-125 and Pd-103 seeds. 

Materials: We randomly selected twenty patients with organ confined 

prostate cancer previously implanted with I-125 seeds in our institution, and 

re-planned these patients with Cs-131 (Model CS-1), I-125 (Model 6711) and 

Pd-103 (Model Pd-200) seeds to prescribed doses of 115 Gy, 145 Gy and 125 

Gy respectively using Prowess Brachytherapy 3.0 treatment planning system. 

The seed strengths employed were 1.8u (Cs-131), 0.5u (I-125) and 1.8u 

(Pd-103). The prostate, prostatic urethra and anterior wall of rectum were 

contoured on trans-rectal ultrasound images with no margin applied for PTV. 

For each case, three optimized treatment plans were generated by automatic 

loading and minor adjusting with identical contours of structures by the same 

medical physicist. The planning goals attempted were V100 (the percentage 

volume of the prostate receiving 100% of the prescribed doses) ~95%, 

D90 (the percentage dose received by 90% of the prostate volume) ≥100%, 

and prostatic urethra UD10 (the percentage dose to 10% of the contoured 

urethra)≤150%. For the plan comparison, we also computed prostate V200, 

V150, prostatic urethra UD30, rectum RV100 (the volume of contoured rectum 

receiving 100% of the prescribed doses). Number of seeds and needles 

were also counted. 

Results: The median prostate volume was 26.0cc (range 13.0cc to 66.1cc). 

The results of the study are summarized in table 1. A typical transversal 

seeds and dose distributions are shown in figure 1. As compared to Pd-103 

and I-125, Cs-131 improved the dose homogeneity and sparing of urethra 

and rectum. The average V150 decreased from 45.3% (Pd-103) and 39.6% 

(I-125) to 35.1% (Cs-131). The average UD10 decreased from 137.6% and 

123.9% to 122.5%. The average rectum RV100 decreased from 0.32cc and 

0.16cc to 0.12cc. In addition, the number of seeds decreased 12.5% and 

3.8%, the number of needles decreased 5.6% and 2.1% compared to Pd-103 

and I-125 seeds, while maintaining an average D90 of 107%, and V100 of 

95.0% or so for the three isotopes. 

Conclusions: From a view point of dosimetry, permanent prostate 

brachytherapy utilizing Cs-131 seeds allows for better dose homogeneity and 

sparing of urethra and rectum while providing comparable prostate coverage 

compared to I-125 or Pd-103 seeds with comparable or less seeds and 

needles. Further biological and clinical studies associated with Cs-131 are 

warranted. 

1309 poster 

DOSIMETRIC OPTIMISATION USING AN ATLAS-BASED AU- 

TOMATIC SEGMENTATION FOR THE DELINEATION OF BRAIN 

ORGANS AT RISK WITH CYBERKNIFE VERSUS 3D RADIOTHER- 

APY 

J. Thariat 1 , G. Malandain 2 , K. Benezery 1 , S. Marcié 1 , P. Y. Bondiau 1 

1 CENTRE LACASSAGNE, Radiation Oncology, Nice, France 

2 INRIA, Sophia Antipolis, France 

Purpose: Intracranial stereotactic Cyberknife radiotherapy (CK) can deliver 

high doses per fraction to brain tumors while limiting the dose to surrounding 

organs at risk (OAR). Fourth generation Cyberknife is equipped with a tumor 

tracking system that uses bony structures with submillimetric accuracy. Brain 

structures have not been evaluated specifically for their role on radio-induced 

adverse effects. Thalami, for example, are involved in alertness, learning, 

memory and motor functions. Multi-modal imaging is used routinely for accurate 

delineation during 3D radiotherapy. An atlas-based automatic segmentation 

has been implemented in the clinic for the delineation of brain OAR 

(Bondiau 2004). Inverse planning allows dosimetric optimisation to achieve 

high doses to the target and very low doses to surrounding tissues. There are 

some uncertainties extrapolating the linear quadratic model for doses over 8 

Gy per fraction. It was speculated that the higher conformity index of the Cyberknife 

technique would compensate for hypofractionation on the OAR and 

that dose escalation would be advantageous on the tumor. 

Materials: Millimetric planning CT and T1-T2 gadolinium-enhanced MRI 

were fused. The atlas was imported into the 3D Treatment Planning System 

(TPS) (Dosisoft TM -OTP) and CK TPS (Inview TM , MultiPlan TM ). We compared 

the doses to 2% of the volume of each of the OAR delivered with a Cyberknife 

hypofractionated escalation schedule to the tumor to that with a conventionally 

fractionated 3D radiotherapy: 3D in 2Gy-fractions (f)-54Gy and 18Gy/f- 

54Gy (simulated plan) for a case of temporo-frontal multiform glioblastoma. 

Results: Delineation of brain OAR was automatically performed. Atlas importation 

was feasible from Dosisoft TM into Multiplan TM through network connections. 

Mean ratios (mean 0.15; range 0.002-0.496) for maximal biologically 

equivalent doses (BED) (table) to the OAR (dose/OAR and /f

1310 poster 

FOR PROSTATE IMRT USING A BEAM MODULATOR, IS THE USE 

OF 6MV PHOTONS SUPERIOR, INFERIOR OR EQUIVALENT TO 

10MV PHOTONS? 

S. Derbyshire 1 , A. Morgan 1 , R. Thompson 1 , D. Thwaites 1 

1 ST JAMES INSTITUTE OF ONCOLOGY, Department of Medical Physics and 


Purpose: To determine the optimum energy for prostate IMRT treatments 

using an Elekta Beam Modulator linear accelerator, in order to inform decisions 

about energy and beam arrangement when commissioning IMRT for 

prostate cancer. No literature currently exists regarding IMRT planning using 

the XiO treatment planning system for delivery with a Beam Modulator 

treatment head. 

Materials: CMS XiO (v4.33.02) was used to create IMRT plans for an 

intermediate-risk prostate patient that satisfied all requirements of the Conventional 

or Hypofractionated High Dose Intensity Modulated Radiotherapy 

for Prostate Cancer (CHHiP) trial protocol, using test patient data from the 

trial QA information. Arrangements with 3, 5, 7, 9 and 11 equally spaced 

fields, containing both a direct anterior and a direct posterior beam were used, 

with both 6MV and 10MV photons. The effects of varying IMRT planning parameters 

(maximum number of iterations, leaf increment, number of discrete 

intensity levels, minimum segment size) were investigated. Treatment plans 

were compared in terms of isodose distributions, conformity indices for targets 

and critical structures, target dose homogeneity, body dose and plan 

complexity. Dosimetric verification was performed on selected plans using a 

Semiflex 0.125cc ion chamber and EDR2 film. 

Results: Target dose conformity and homogeneity and sparing of critical 

structures improved with an increasing number of beams, although any improvements 

were small for plans containing more than five fields. Set-ups 

containing a direct posterior field provided superior conformality around the 

rectum compared to anterior beam arrangements. Mean non-target dose 

and total number of monitor units were higher with 6MV for all beam arrangements. 

The dose distribution resulting from seven 6MV beams was considered 

clinically equivalent to that with five 10MV beams. Ion chamber measurements 

were initially consistently 5% lower than doses calculated by XiO, 

but gamma analyses on composite films showed good agreement between 

relative dose distributions for both energies. Further work has demonstrated 

the criticality of accurate leaf position calibration in IMRT delivery. 

Conclusions: IMRT treatments have been successfully delivered using a 

Beam Modulator, having developed planning methods with XiO to fulfil demanding 

dose criteria using many different set-ups. A number of plan evaluation 

parameters have been explored and related to clinical decisions. This 

study suggests that 6MV photons can produce a prostate IMRT plan that 

is comparable to one using 10MV photons, provided a sufficient number of 

fields is used to avoid high-dose regions near beam entry points. Although 

using 6MV slightly increases treatment calculation and delivery times and the 

number of QA measurements, it is preferred to avoid commissioning a second 

energy for IMRT. Work is ongoing to resolve the dose discrepancy and 

develop a clinical class solution. 

1311 poster 

HYPERTHERMIA TREATMENT PLANNING TARGETS HEATING TO 

THE TUMOR. 

G. van Rhoon 1 , M. Paulides 1 , J. Bakker 1 , N. Kuster 2 , E. Neufeld 2 , C. 

van der Zee 1 , P. Levendag 1 


2 IT’IS FOUNDATION, Zurich, Switzerland 

Purpose: The enormous progression in computational power and tremendous 

improvements in the available software for 3-D EM-modeling offer 

unique possibilities to enhance the quality of the hyperthermia treatment. 

The presently available advanced hyperthermia treatment planning systems 

provide an excellent opportunity to calculate 3D SAR- or temperature distributions 

and derive predicted HT-dose parameters from these distributions, as 

well as design and construction of a hyperthermia applicator for targeted heating 

of advanced carcinomas. At the same time such progress would strongly 

simplify translation of knowledge from experienced to less-experienced or 

new hyperthermia centers (education). 

Materials: An FDTD simulation package (SEMCAD-X, Schmid & Partner Engineering 

AG, Zrich, Switzerland) is used to predict the SAR distributions for 

various arrays of Lucite cone waveguide applicators. The 3-D model predictions 

are validated against 3-D measured SAR distributions using the wellaccepted 

gamma-method. In this manner the relative SAR distributions as 

predicted by the FDTD model are transferred to quantitative SAR distributions. 

The feasibility to qualitatively and quantitatively predict the 3-D SAR 

distribution in a realistic anatomy is demonstrated for patients with a tumor 

located on the chest wall. The HT field involves all macro- and microscopic 

tumor and should cover the whole RT-field. Additionally, high-resolution 3D 

electromagnetic (EM) simulations were used to perform parameters studies 

that were used to guide the design of the most suitable applicator setup. 

Results: In patients with non-standard treatments fields, qualitatively hyper- 


S 417 

thermia treatment planning was successfully used to support decision making 

with regard to the treatment strategy. Further, an excellent quantitative agreement 

was found between the measured and predicted 3-D SAR distribution. 

Next a quantitative 3-D SAR distribution was predicted for a patient treated 

by a 2x2 array of LCAs. It is shown that such an umbrella-style array configuration 

basically represents a "heating the base" approach: the applicators 

deposit most their EM power at the tissue below their footprint. The new Head 

and Neck applicator ‘HyperCollar‘ has been used to heat tumors of the larynx, 

base of tongue as well as very recently for nasopharyngeal tumors. Extensive 

treatment planning with EM simulations preceded the clinical treatment and 

showed that the focus can effectively be steered towards the target region. 

Conclusions: The result of this explorative study demonstrates that advanced 

EM-modeling, in this case using the SEMCAD-X model, provides 

reliable predictions of SAR patterns of various applicators. 

1312 poster 

IMPLEMENTATION OF 2007 ESTRO/EAU/EORTC RECOMMENDA- 

TIONS ON PROSTATE BRACHYTHERAPY 

P. Bownes 1 , G. Wright 1 , A. McCabe 1 , J. Bowden 1 , B. Al-Qaisieh 1 


Kingdom 

Purpose: To assess whether current clinical practice at St James’s Institute 

of Oncology-Leeds meets the requirements of the new ESTRO/EAU/EORTC 

guidelines. 

Materials: 20 patients were randomly selected for this study. Variseed TM 7.1 

treatment planning system (TPS) was used to generate treatment plan (preplan) 

using the standard Leeds planning protocol. Once the plans had been 

approved by the oncologist, the same 20 plans were then given to a radiologist 

who contoured the prostatic urethra and re-contoured the rectum following 

the recommendations of the new guidelines. Furthermore, using TPS automatic 

margin-growing algorithm the PTV was grown in accordance with the 

new guidelines. Without making any modifications to the existing seed configuration, 

the dosimetric indices associated with these new structures were 

compared to the requirements of the new guidelines. A different 20 patients’ 

CT scans have been randomly selected. The TPS was used to generate post 

implant dosimetry and quality indices were reported using the standard Leeds 

criteria. Without making any modifications to the existing seed configuration, 

the same 20 CT scans were used to report the dosimetric indices according 

to the new guidelines. Quality indices of both criteria were compared. 

Results: The results show that all the plans meet the current requirements. 

Three prostatic dosimetric indices indicate under-dose, although even for 

VP150 which exhibits the greatest degree of under-dose, the mean modulus 

discrepancy is less than 2% and at most 5.2%. In contrast, more discrepancies 

between the selected plans and the new guidelines were noticed in 

urethral dose; the limit on DU30 is exceeded by 11% on average, and by 

22.9% maximum. The DU10 limit is exceeded by an average of 4.2% but in 

some cases this limit has been met. The rectal DR2cc constraint is met by all 

plans. The post-plan dosimetry results show that CT images give variable results 

depending on the specific parameter and contour being assessed when 

compared to CT-MR fusion. 

Conclusions: In implementing the new guidelines, any change in clinical 

practice should be done with great care. Clinical outcome ultimately depends 

upon the implantation itself.


1313 poster 

IMPROVEMENT TREATMENT PLANNING PROCESS FOR HEAD 

AND NECK RADIATION THERAPY 

M. do Carmo Lopes 1 , B. Costa Ferreira 2 , J. Mateus 1 , M. Capela 1 

1 



2 

I3N - UNIV. AVEIRO, Fisica, Aveiro, Portugal 

Purpose: To compare the conventional treatment technique for patients with 

head and neck tumours with an improved forward planning technique (IFP) 

and two IMRT techniques using different fractionation schemes. 

Materials: A retrospective planning study was made using data from seven 

patients. The PTV1, PTV2 and PTV3 included the primary tumour, the high 

and low risk lymph nodes, respectively. Except for the conventional technique 

where a maximum dose of 64.8Gy was prescribed to the PTV1, 70.2Gy, 

59.4Gy and 50.4Gy were prescribed respectively to PTV1, PTV2 and PTV3. 

The main organs at risk were the spinal cord, the parotids and the mandibula. 

The conventional technique used a combination of lateral and oblique photon 

and electron beams to irradiate the PTV2 and PTV3 with blocks to protect 

the spinal cord. The boost was composed by 2 or 3 oblique photons 

beams to irradiate the PTV1. The IFP technique used 5 to 7 irradiation directions 

with a total number of beams of 15 to 21, in an irradiation strategy that 

spared as much as possible the critical organs. The IMRT techniques used 

5 to 9 equidistant photons beams of 6MV. The first technique, IMRT1, was 

prescribed with the conventional fractionation scheme of 1.8Gy per fraction 

during 39 fractions. The second IMRT technique, IMRT2, simultaneously irradiated 

the PTV2 and PTV3 with 59.4 and 50.4Gy, respectively, during 28 

fractions, and then the PTV1 was boosted with 6 fractions of 1.8Gy. Plan 

evaluation was based on DVH analysis and isodoses. 

Results: A significant improvement in the quality of the plan was possible with 

the IFP technique compared with the conventional one. A dose escalation 

in the tumour from 64.8Gy to 70.2Gy was possible while reducing the mean 

dose in the parotids by 8Gy and keeping the maximum dose in the spinal cord 

below 45Gy. No significant dosimetric advantages were obtained between 

the 2 IMRT techniques investigated. But with IMRT a further dose reduction 

in the parotids, of around 9Gy in the ipsilateral and 5Gy in the contralateral 

parotid, was obtained at the same time that target coverage was improved. 

Conclusions: Due to the significant improvement in dose conformality obtained 

with the IFP technique, this beam arrangement is used in the clinical 

routine while implementing IMRT. The practical and biological advantages of 

the dose painting technique IMRT2, with a shorter treatment time, may outweigh 

the small dosimetric differences between the two IMRT techniques and 

it is already being used for selected patients. 

1314 poster 

IMPROVING THE EFFICACY OF THERAPY PLANNING IN IMRT BY 

ELABORATION OF TEMPLATE OF INITIAL CONSTRAINTS 

L. Szczurek 1 , A. Skrobala 1 , T. Piotrowski 1 

1 GREAT POLAND CANCER CENTRE, Department of Medical Physics, 

Poznan, Poland 

Purpose: To develop a template of initial constraints for organs at risk (OAR) 

used during IMRT optimization for patients with larynx cancer and validate 

the methodology through evaluation DVH for a group of patients. 

Materials: IMRT plans with sliding windows technique were produced for 15 

patients with larynx cancer (T1-3 N12b M0) to irradiate the larynx (PTV2) 

and bilateral lymph nodes (PTV1) up to 50Gy in 25 fractions in first phase, 

followed by 10Gy in 5 fractions added to PTV2 in second phase. PTV1 and 

PTV2 were determined by adding the 0.5cm of tissues around the CTVs. The 

PTV1 and PTV2 were moved 3mm away from the skin to avoid build-up effect. 

The final DVH for each patient was obtained through the process of tightening 

the constraints and increasing the priorities for each volume. The validation 

of the methodology was done through evaluating the final DVHs for a group 

of patients. 

Results: The initial constraints for doses in target volume were: median dose 

of 50Gy in first (PTV1 and PTV2) and 10Gy in the PTV2 in second phase 

with priority 600 and 650 respectively. The respective priorities and maximum 

doses were defined: spinal cord 850 and < 44Gy, brain stem 350 and

tion, albeit by itself it has lower weight than proliferation. However, when it is 

associated with proliferation it could easily lead to treatment failure following 

an underdosage of the trouble foci. Treatment optimisation however could 

improve both tumour control and normal tissue sparing. 

Conclusions: The results of this study have provided a useful insight into 

the factors that could influence the inclusion of proliferation information into 

treatment planning. Furthermore, they have shown that the individualisation 

of the treatments based on imaged proliferation could lead to improved outcome 

while creating the premises for normal tissue sparing. 

1317 poster 

INCREASING THE ABILITY OF ARC TREATMENTS TO PRODUCE 

SHARP CHANGES IN DOSE DISTRIBUTION BY VARYING ROTATION 

AXIS 

J. Nord 1 , J. Peltola 1 

1 VARIAN MEDICAL SYSTEMS FINLAND, Applied Research, Helsinki, Finland 

Purpose: The purpose of this work was to study the effect of rotation axis 

in the ability to reproduce complex shapes. Organs and other structures in 

treatment plans may contain sharp changes in shape. These sharp changes 

may include contouring noise in direction perpendicular to imaging plane or 

small organs, such as optic nerve. 

Materials: A RapidArc TM (a form of volumetric modulated arc therapy, Varian 

Medical Systems) optimization method was used to optimize plans with sharp 

changes in shape. These plans were optimized using different rotation axes. 

The ability to create dose distributions that follow accurately the prescribed 

shapes was evaluated directly from isodose levels. 

Results: The isodose levels followed more accurately the target shape, when 

the sharp changes in shape were perpendicular to the rotation axis. With 

perpendicular setup the volume of region with over 95 % of prescribed dose 

outside target was 7.68 cm 3 . With 45 degrees titled setup the volume was 

11.44 cm 3 , 49 % more than with perpendicular setup. The volume of target 

was 46.55 cm 3 . 

Conclusions: Arc treatments are better in producing sharp changes in dose 

distribution in direction that is perpendicular to the rotation axis. 

1318 poster 

IS THERE A CORRELATION BETWEEN SIZE OF PLANNING 

TARGET VOLUME (PTV) AND MONITOR UNITS IN IMRT? 

I. Das 1 , C. W. Cheng 2 , P. Johnstone 3 

1 

UNIVERSITY OF PENNSYLVANIA, Radiation Oncology, Philadelphia PA, 

USA 

2 

MORRISTOWN MEMORIAL HOSPITAL, Radiation Oncology, Morristown, NJ, 

USA 

3 

INDIANA UNIVERSITY MEDICAL SCHOOL, Radiation Oncology, Indianapolis, 

USA 

Purpose: Treatment planning systems (TPS) for IMRT have evolved to a 

greater sophistication, with a faster convergence of the cost function in the 

dose-volume constraints for adequate dose coverage with fewer segments. 

IMRT however, produces relatively large (3-7 times) monitor units (MU) compared 

to forward planning in most TPS. Higher MU gives stray radiations that 

may add to the whole body dose and long term complications. An analysis 

of the correlation between MU and target volume is presented with possible 

explanation for the deviations. 

Materials: Analysis of 142 patients treated IMRT (brain, 2%; head and neck, 

9% and prostate, 89%) was performed retrospectively on two TPS. All of 

these patients were treated with seven evenly spaced coplanar IMRT fields 

with either 6 or 15 MV beams. The criteria on maximum number of segments 

(≤100), minimum MU/segment (≥2), and minimum area/segment (≥2 cm 2 ) 

were set for planning and strictly followed. The planning target volume (PTV), 

total MU and number of segments were recorded for initial and cone down 

(CD) portions of the treatment plan. The frequency distribution of the area of 

the segments in each field and MU were also analyzed. 

Results: The intuitive observation that large target volume has larger number 

of segments and hence more MU for a given dose has been observed 

in most IMRT plans. However, sixteen percent (23/142) of the patients were 

found to have larger MUs for smaller target volume in the CD fields for the 

same prescribed dose and the same beam arrangement. The MU reversal 

was confirmed by additional quality assurance by repeated planning. Figure 1 

shows the total MU versus PTV volume for both the original and CD treatment 

courses for these patients. The variation of MU versus volume clearly exhibited 

variable trends, independent of the TPS and disease site. The number 

of segments is not correlated with MU in either of the original course or the 

CD. The frequency distribution of the area in CD segments showed tendency 

towards smaller segments indicating that it is the number of the small area 

segments that are mainly responsible with lower scatter factor (Scp) hence 

producing higher MU. 

Conclusions: In general, a large PTV requires higher MU depending on the 

location PTV with respect to the organs at risk. However there is a subset 

of patients where this is reversed, and a small volume needs larger MU. This 


S 419 

may lead to a higher whole body dose, especially with higher energy beams. 

This reversal could be explained on the basis of frequency distribution of the 

small size segments needed to treat smaller PTV; since the output of a machine 

decreases as field size is reduced. The relatively higher frequency of 

smaller size segments in smaller volume PTV requires higher MU. To eliminate 

such abnormalities, TPS should provide tools to calculate and display 

the frequency distribution of the segment size for evaluating the quality of an 

IMRT plan. 

1319 poster 

MONTE CARLO CALCULATED ELECTRON MLC (EMLC) FIELDS 

COMBINED WITH PHOTON IMRT IMPROVES DOSE DISTRIBU- 

TIONS IN POST-MASTECTOMY RADIOTHERAPY 

T. Vatanen 1 , E. Traneus 2 , T. Lahtinen 3 

1 KUOPIO UNIVERSITY HOSPITAL, Department of Oncology, Kuopio, Finland 


3 UNIVERSITY OF KUOPIO, Department of Physics and Department of 

Oncology , Kuopio, Finland 

Purpose: Due to the interaction of electrons with tissue inhomogenities the 

treatment planning with electron beams is more complicated than with photons. 

Widely used pencil beam algorithms are inferior compared with the recent 

clinical MC based electron dose calculations. In the most frequent electron 

field application, post-mastectomy radiotherapy (PMRT) in breast cancer 

patients, the treatment fields are seldom calculated. Recently, we demonstrated 

with electron MC calculation that dose distributions in PMRT are far 

from uniform, with the presence of cold and hot spots. In the present investigation, 

we applied the MC-based electron treatment planning and eMLCshaped 

electron fields in PMRT. With the goal of receiving uniform dose distributions 

in the chest wall and surrounding lymphatics the electron field to the 

scar area of PTV was calculated first and the rest of the PTV were completed 

with the use of photon IMRT. 

Materials: Dose distributions from the Oncentra MasterPlan TPS were calculated 

for 5 breast cancer patients after modified radical mastectomy. The 

mixed beam treatment with electrons and photons consisted of anterior electron 

fields plus anterior-posterior and tangential photon fields. For the eMLC 

field a beam model based on a multi-source beam characterization was used. 

The extension to eMLC field shaping was implemented in a prototype version 

of the TPS. The eMLC prototype with 2 cm thick steel leaves and a sourceto-leaf 

distance 97.2 cm was attached under the 20x20 electron applicator of 

Varian 2100 C/D linac. The 6 MV photon step-and-shoot IMRT was optimized 

with four to six fields calculated with collapsed cone algorithm. 

Results: In all patients the dose coverage in PTV improved with the mixed 

beams and cold spots at electron-photon field interface reduced. The mean 

PTV and OAR doses were slightly higher for the mixed beam plans compared 

to conventional non-IMRT technique. 

Conclusions: Dose conformity in the chest improved with the use of combined 

electron eMLC and photon IMRT fields. The improved PTV coverage 

leads to a slight increase in the lung and heart doses. 

1320 poster 

OBTAINING A HIGHER TUMOR DOSE IN RADIOSURGERY WITH- 

OUT COMPROMISING NORMAL TISSUE 

J. van Santvoort 1 , R. Wiggenraad 2 , A. Verbeek 2 

1 

MEDICAL CENTER HAAGLANDEN, Clinical Physics, The Hague, Netherlands 

2 

MEDICAL CENTER HAAGLANDEN, Radiotherapy, The Hague, Netherlands 

Purpose: Radiosurgery dose levels for treatment of brain metastases are 

often based on results of the RTOG 90-05 study. This means that larger 

target volumes receive a lower dose (15 Gy minimum dose) in order to limit 

toxicity. As a result, failure rates are higher for this group.It was also observed 

that failure rates were lower for Gamma Knife treated patients than for Linac


treated patients. An obvious difference between these two modalities is the 

dosage: for most Gamma Knife plans dose is prescribed to the 50% isodose 

while for most Linac plans this is done for the 80% isodose. This results in 

a different dose distribution within the target volume.In this study we want to 

find a prescription isodose and dose level that results in a higher target dose 

without compromising normal tissue. 

Materials: For five patients with brain metastases the CTV (the visible volume 

on MRI) was contoured. A 2 mm margin was added to create the PTV. 

The PTV size ranged from 1 to 15 cc. Normal brain was contoured as the 

total brain minus the CTV. Treatment plans, using a dynamic conformal arc 

technique, were made for which either the 50, 60, 70 or 80% isodose encompassed 

the PTV.From the DVHs of these plans, gEUDs (generalized Equivalent 

Uniform Doses) for CTV, PTV and for normal brain were calculated. 

Also isocenter dose was calculated. Then for all plans the prescription dose 

is set at such a level that the normal brain gEUD is identical to the original 

plan, which was prescribed to the 80% isodose. This new combination of 

prescription dose and isodose results in a different gEUD for CTV and PTV 

and isocenter dose. 

Results: For both the 70 and 60% plans, the PTV gEUD is on average 3% 

higher than for the original plan. For the 50% plan the PTV gEUD is 1% lower. 

For the 70, 60 en 50% plans, the CTV gEUD is higher by respectively 8, 15 

and 22% and the isocenter dose by 10, 20 and 36% (see figure). 

Conclusions: The optimal prescription percentage appears to be 60% combined 

with a 11% lower prescription dose: for these values the gEUD for the 

PTV is 3% higher and for the CTV 15%. The isocenter dose is 20% higher. 

Prescribing to an even lower percentage results in a lower PTV gEUD.This 

new dosage scheme results in a higher target dose without a higher normal 

brain gEUD. 

1321 poster 

OPTIMISATION OF BEAM ORIENTATIONS FOR INTENSITY- 

MODULATED RADIOTHERAPY (IMRT) 

K. Gerard 1 , V. Marchesi 2 , X. Franceries 3 , F. Husson 4 , A. Noel 1 , H. 

Kafrouni 4 , P. Aletti 1 

1 

CENTRE ALEXIS VAUTRIN, CRAN, NANCY-UNIVERSITY, CNRS UMR 

7039, Medical Physics, Vandoeuvre-les-Nancy, France 

2 

CENTRE ALEXIS VAUTRIN, Medical Physics, Vandoeuvre-lès-Nancy, 

France 

3 

INSERM UMRS 825, Toulouse, France 

4 

DOSISOFT S.A, Cachan, France 

Purpose: Although successfully used for prostate and head-and-neck cancer 

treatments, IMRT routine clinical implementation is partially held back 

by the time required to perform treatment planning.All current inverse Treatment 

Planning Systems (TPS) allow the optimisation of the fluence maps, but 

the choice of the gantry angles is generally left to the expertise of the user. 

This implies that numerous trial-and-error attempts are needed to produce 

an acceptable treatment plan that may not be the optimal solution.This study 

presents a patient-specific algorithm that optimises the beam angles for each 

IMRT treatment.The aim is to evaluate this algorithm by comparing the results 

to those obtained manually by the physicist, based on experience and 

intuition. 

Materials: The simplex algorithm has been implemented in the ISOgray TPS 

(DOSIsoft S.A, France), to optimise the beam orientations. The aim is to 

automatically determine the optimal beam orientations, thereby achieving 

the best compromise between target volume coverage and sparing organs 

at risk, while taking into account the results of the fluence map optimisation. 

The simplex has to find the beam configuration that best fits the clinical 

goals fixed by the physician, using a dose-volume based objective function. 

For each new beam arrangement evaluated by the simplex, intensity profiles 

are optimized.To compare the overall treatment quality achieved by the simplex 

algorithm versus the physicist’s manual solution, treatment plans (50Gy 

prescribed) were calculated with both modalities for 5 head-and-neck cancer 

patients covering different tumour sites: oropharynx, epiglottis and base 

of tongue. In these cases the main organs-at-risk are: the spinal cord, the 

parotid glands and the brainstem. 

Results: For the 5 head-and-neck treatment plans we tested, the beam arrangements 

were different when using either the automatic (simplex) or manual 

(physicist) method, and similar or better dosimetric results were obtained 

when the simplex method was used: a better coverage of the tumour volume 

and a reduction of the dose to surrounding organs-at-risk. Indeed, the 

dose-volume histograms obtained from the simplex results showed that the 

dose received by 95% of the tumour volume has been slightly increased: from 

48Gy to 48.5Gy on average. Concerning the organs at risk, for the 5 patients, 

the mean dose received by both parotid glands has been reduced by 1Gy 

on average (i.e 5%) and the maximum dose received by the spinal cord has 

been reduced by 0.6Gy on average (i.e 1.2%). Finally, the dose received by 

the brainstem has been significantly reduced from 47Gy to 43Gy on average 

(i.e 9.2%). 

Conclusions: The use of the simplex algorithm for optimising the beam angles 

gave similar or better dosimetric results than the physicist’s manual beam 

arrangement. Moreover, in routine clinical use, it would significantly reduce 

the workload for IMRT treatment planning. 

1322 poster 

PHYSICAL ASPECTS OF VOLUMETRIC MODULATED ARC THER- 

APY (VMAT) USING ELEKTA SYNERGY AND ERGO++ TREATMENT 

PLANNING SYSTEM 

A. Haga 1 , K. Nakagawa 1 , K. Shiraishi 1 , K. Ohtomo 1 , Y. Okano 1 , T. 

Oritate 1 , K. Yoda 2 , R. Pellegrini 3 

1 UNIVERSITY OF TOKYO HOSPITAL, Department of Radiology, Tokyo, Japan 

2 ELEKTA KK, Medical Physics, Kobe, Japan 

3 ELEKTA SPA, 3D Line Research Development s.r.l., Agrate Brianza (MI), 

Italy 

Purpose: Volumetric Modulated Arc Therapy (VMAT) has been implemented 

on Elekta Synergy using ERGO++ treatment planning system (TPS), and 

various physics tests have been performed including verification of isocenter 

dose and dose distribution. 

Materials: To modulate beam intensity during dynamic conformal arc delivery, 

dose rate and gantry speed are varied based on optimized MUs for all 

divided arcs. ERGO++ TPS can optimize MUs according to the prescription 

given for the inverse planning. Each collimator angle for each control angle 

is separately optimized to maximize conformity. Dose was delivered to a water 

phantom in a cylindrical acrylic enclosure. Then, the isocenter dose was 

mesured by a pin-point chamber and it compared with the calculated one. In 

order to verify the dose distribution, also, an EDR2 films were placed inside a 

multi-layer acrylic phantom and they were compared with calculated one. For 

DMLC verification in VMAT test, the isocenter dose with various speed in MLC 

open and shut was measured without varying dose rate, while the isocenter 

dose with varying dose rate in each small angle arcs was measured with 

static MLC. 

Results: We have confirmed MLC leaves, collimator angles, gantry speed, 

and dose rates have been all varied during gantry rotation. The isocenter 

dose descripancy was within our guideline of +/- 3 % while measured dose 

profile on a film had a discrepancy of +/- 3 % for most regions having a dose 

over 50 % of isodose. Isodose contours between calculation and meacurement 

agreed withing a distance of 2 mm for most regions having a dose over 

50 % of isodose. 

Conclusions: We have tested VMAT delivery and confirmed that the beam 

intensity was modulated as planned by the TPS. 

1323 poster 

POST-IMPLANT DOSIMETRY AND SIDE EFFECTS AFTER PERMA- 

NENT I125 PROSTATE BRACHYTHERAPY. STUDY OF A SUTHERN 

ITALY HOSPITAL 

S. Clemente 1 , M. Mazziotta 2 , P. Piernicola 2 , G. Castaldo 1 , L. Lapadula 

1 , A. Montagna 1 , L. Rago 1 

1 

ONCOLOGICAL HOSPITAL, Department of Radiotherapy Oncology, Rionero 

in Vulture (Pz), Italy 

2 

ONCOLOGICAL HOSPITAL, Service of Medical Physics, Rionero in Vulture 

(Pz), Italy 

Purpose: Implantation of the prostate with I-125 seeds is well-established 

treatment for early-stage prostate cancer. The only Hospital of the Southern 

Italy to perform this implant is our. The aim of this study was to investigate the 

changes in anatomy for prostate, post-implant dose distribution and long-term 

urinary, bowel and sexual function after I-125 brachytherapy. 

Materials: Between 2003 and 2007, 71 men (mean age 72) underwent transperineal 

TRUS guided I-125 prostate brachytherapy in our Hospital. Criteria 

for selection were: good performance status, localized tumor (T1, T2a-T2b), 

moderate or well differentiated, ultrasound measured prostate volume>20cc 

and

plane CT image of the pelvis were obtained approximately 30 days after the 

implant. For each postimplant plan, dose-volume histograms for prostate, rectum 

and urethra were generated. The experience in terms of side effects (urinary 

incontinence/irritation, bowel and sexual functions) were investigated. 

Results: The mean prostatic volume at implant was 29±8cc, this initial volume 

was nearly reached at day thirty, 34±8cc. The dose covering 90% 

of the prostate volume, the prostate volumes reached by 100% and 150% 

of prescription dose were 130±20Gy, 78±12% and 55±12% respectively. 

The rectum volumes reached by 50% and 100% of the prescription dose and 

dose covering 0.1cc and 2cc of rectum were 1.2±0.5cc, 0cc, 103±30Gy and 

67±17Gy. The urethra volume reached by 150% of the prescription dose was 

0.4±0.4cc. The follow-up schedule was four to six weeks after treatment, 6 

monthly after. Urinary irritation and bowel symptoms lasted for few months 

before settling near to pre-treatment levels. Urinary incontinence is a rare 

event. For a small percentace (0.5%) sexual function is reduced with time, 

may be due to late effects of brachytherapy and/or age related decline. 

Conclusions: This work is limited in that it describes the experirence of single 

Hospital. Respect to other published data in the literature D90 and V100 

dose level of the prostate volume are lower, this may be a consequence of 

inaccurate feedback of prostate volumes defined on CT post-implant imaging. 

In our Hospital a CT/MRI fusion method is now performed for better determining 

the prostate volume and dose volume histogram. 

1324 poster 

POTENTIAL OF ELEKTA VMAT FOR HEAD &NECK TREATMENT 

P. Ambolt 1 , A. Morgan 1 , D. Thwaites 1 


Kingdom 

Purpose: For head and neck patients with cancer of the tonsil and bilateral 

disease, step and shoot IMRT is currently used in this centre, delivered on 

Elekta linacs. This enables higher target doses than with our conventional 

technique, which is limited because of cord tolerance, and it also enables 

simultaneous integrated boost and parotid sparing. The IMRT plans normally 

meet our prescription criteria, but the treatment times for these complex cases 

are problematic and for some patients may be a limiting factor for the plan 

quality that can be achieved. Dynamic intensity modulated arc therapy (IMAT) 

has the potential for further improving target coverage and organ at risk (OAR) 

sparing whilst reducing treatment times, thus providing a better treatment for 

the patient. The centre is installing and testing Elekta’s Volumetric Modulated 

Arc Therapy (VMAT) functionality. This preliminary planning study aims to 

test the feasibility of VMAT for head and neck patients. 

Materials: The CMS XiO (ver. 4.33.02) treatment planning system is currently 

used for IMRT planning. The class solution for these patients delivers 

5 equally spaced beams. As a first approximation of full rotation VMAT, IMRT 

plans with 24 beams in 15 ◦ increments have been planned on XiO for an 

already-treated IMRT patient. Due to memory problems, 36 beams at 10 ◦ 

increments are not currently possible to simulate full rotation, but plans with 

27 beams at 10 ◦ increments were also produced, simulating a 260 ◦ arc running 

from gantry angle of 235 ◦ to 135 ◦ . These plans are compared to our 

current IMRT approach and work is beginning to compare to VMAT plans using 

the Elekta ERGO TPS. On completion of the planning studies, plans are 

to be delivered to a phantom for dosimetric assessment and treatment time 

studies. 

Results: Preliminary results show the simulated VMAT plans to have better 

target coverage and better dose homogeneity than current IMRT plans, with 

similar OAR sparing. As an example of this the nodal PTV coverage of the 

95% isodose improved from 95.5% for the standard IMRT plan to 98.2% and 

97.1% for the 24 and 27 beam plans respectively. The conformity index for 

the primary PTV is observed to change from 0.500 for the standard IMRT 

plan to 0.529 and 0.551 for the 24 and 27 beam plans respectively. 

Conclusions: Intensity modulated arc therapy using the Elekta VMAT solution 

can potentially improve patient plan quality and are likely to make delivery 

more efficient. 

1325 poster 

QA OF THE OPTIMIZER: DOES A LONGER PATH LEAD TO A 

BETTER SOLUTION? 

J. Vanregemorter 1 

1 UNIVERSITAIR ZIEKENHUIS ANTWERPEN, Radiotherapy, Antwerp, Belgium 

Purpose: The beamlet optimizer from Tomotherapy does not have a stop feature 

that is based upon an objective criteria like a cost function. The number 

of iterations before a full dose calculation needs to be set prior to the start of 

the calculations or the full dose calculation can be manually started after any 

arbitrary number of iterations. This study reports on the comparison of the resulting 

dose volume histograms and the match between the dose distribution 

predicted by the calculations and the actually measured dose distribution for 

different numbers of iterations. 

Materials: A clinical case (a boost of 10 fractions of 20Gy) was recomputed in 

three ways. For all three, a first beamlet optimisation followed by a final dose 


S 421 

calculation was performed with 40 iterations using the appropriate constraints 

for organs at risk. This was then followed by a second beamlet optimisation 

with in addition strong constraints for the target volumes for a number of 20, 

100 and 3500 iterations respectively followed by a full and final dose calculation. 

Results: Although the dose volume histograms show a better result the 

higher the number of iterations, this is not reflected in the measurement of 

the delivered dose. For each of the plans, the treatment was recalculated 

on the Tomotherapy cheese phantom and a measurement was made in the 

coronal plane using EDR2 films. All films show a consistent medium dose. 

When evaluated in detail, it can be seen that for the plans with a total of 60 or 

140 iterations the measurement fits nicely the calculated dose. For the plan 

with a total of 3540 iterations however, this is no longer the case. The calculated 

profiles seem noisy with little steps of up to 0.05Gy that are not seen 

on the measured profiles. The differences appear both within homogeneous 

dose areas and close to dose gradients. 

Conclusions: In conclusion, extremely long optimisation for the Tomotherapy 

optimizer does result in a better calculated dose volume histogram but not in 

an effective better dose distribution which can give an incorrect impression of 

the dose especially close to steep gradients. 

1326 poster 

RETROSPECTIVE DOSIMETRY STUDY ANALYSING THE ROLE OF 

IMRT IN LOCALLY ADVANCED NON-SMALL CELL LUNG CANCER 

(LA-NSCLC) PATIENTS. 

A. Nulens 1 , A. Mousa 2 , A. Swinnen 1 , P. Dirix 1 , W. De Wever 3 , S. 

Stroobants 4 , Y. Lievens 1 

1 

UNIVERSITY HOSPITAL GASTHUISBERG, Radiation Therapy, Leuven, 

Belgium 

2 

NATIONAL CANCER INSTITUTE UNIVERSITY OF CAIRO, Radiation Therapy, 

Cairo, Egypt 

3 

UNIVERSITY HOSPITAL GASTHUISBERG, Radiology, Leuven, Belgium 

4 

UNIVERSITY HOSPITAL GASTHUISBERG, Nuclear Medicine, Leuven, 

Belgium 

Purpose: To investigate the gain in organs at risk (OAR) dose with IMRT 

compared to 3D-conformal radiotherapy (3D-CRT) in LA-NSCLC patients and 

to determine the potential of this technique in a clinical dose escalation protocol. 

Materials: This retrospective planning study comprises data of 35 LA-NSCLC 

patients with anatomo-pathologically proven mediastinal involvement. Target 

definition was based on PET-positive regions, visually correlated with 

planning CT data. Treatment planning was done with a pencil beam algorithm 

using Eclipse R○. Modified Batho algorithm was used for tissue heterogeneity 

correction. Reference 3D-CRT plans were made with at least 

3 coplanar static 10 megavolt (MV) beams. For the corresponding IMRT 

plans class solutions for right and left sided lesions were created. They consisted 

of 6 coplanar 10MV beams, delivered with a sliding window technique. 

Prescribed dose (PD) was 66Gy/2Gy or lower in case of constraint violation. 

Primary objective was tumour coverage (95% coverage with 95% of 

PD). Secondary objectives included doses to the spinal cord (Dmax


1327 poster 

ROBUST TREATMENT PLANNING TAKING INTO ACCOUNT PET- 

IMAGED HYPOXIA 

J. Uhrdin 1 , I. Toma-Dasu 2 , A. Dasu 3 , S. Roels 4 , P. Dirix 4 , T. Depuydt 4 , 

K. Haustermans 4 , H. Rehbinder 1 , A. Brahme 2 

1 

RAYSEARCH LABORATORIES AB, Stockholm, Sweden 

2 



3 

NORRLAND UNIVERSITY HOSPITAL, Department of Radiation Physics, 

Umeå, Sweden 

4 

LEUVEN UNIVERSITY HOSPITALS, GASTHUISBERG, Radiotherapy, Leuven, 

Belgium 

Purpose: Successful radiation therapy is enhanced by treatment plans that 

address the characteristics of the patient, primarily cell responsiveness to 

dose delivery. Hypoxia is a major factor that determines cell responsiveness, 

and clinical imaging of tumor oxygenation with PET is possible and in fact 

present in the clinical environment. It is the purpose of this study to show that 

FMISO-PET-imaged hypoxia can be incorporated into the treatment planning 

process. 

Materials: Using data on FMISO-uptake as a function of oxygen partial pressure, 

the FMISO-PET-image can be converted into predicted biological response 

and correspondingly into cell survival with a modified Poisson-LQ formula. 

From these a robust approach has been chosen to find less heterogeneous 

optimal dose distributions taking into consideration normal tissue. 

Results: The method of estimating biological response based on PET images 

has been implemented into a software environment suitable for advanced 

radiation therapy, and has been subsequently used for treatment planning 

purposes. The algorithm, using an approach of regional uniform dose 

distribution, is taking into consideration tumor hypoxia while keeping the prescribed 

dose at reasonable levels thus sparing the normal tissue. 

Conclusions: Incorporation of hypoxia information into treatment planning 

software is possible. Dedicated algorithms could account for the heterogeneity 

of hypoxia and estimate reasonable dose levels that could lead to 

increased tumor cure and sparing of the normal tissue. 

1328 poster 

SOFTWARE FOR CLINICAL IMPLEMENTATION OF RADIOBIOLOGI- 

CAL TREATMENT PLAN OPTIMIZATION 

A. Tzikas 1 , P. Mavroidis 1 , B. Lind 1 , A. Brahme 1 



Purpose: The true dose-response relations of the different tumors and normal 

tissues should be estimated and used in the clinic. The aim of this study 

is to demonstrate developed tools that are necessary for determining doseresponse 

parameters of tumors and normal tissues, for clinically verifying already 

published parameter sets using local patient materials and to make use 

of all this information in the optimization and comparison of different treatment 

plans and radiation techniques. 

Materials: One of the software modules is designed to determine the doseresponse 

parameters of tumors and normal tissues. This is accomplished by 

associating the calculated response rates with the clinical follow-up records. 

The 3-dimensional dose distributions and the clinical treatment outcomes are 

introduced into a maximum likelihood fitting to calculate the best estimates 

and confidence intervals of the parameters used by different radiobiological 

models. Another module of this software concerns its ability of evaluating 

the validity of dose-response parameters describing tumor control and normal 

tissue complications. This is accomplished by associating the expected 

response rates, which are calculated using different models and published 

parameter sets, with the clinical follow-up records of the local patient population. 

Finally, the last module of the software is used for increasing the 

likelihood of accomplishing complication-free tumor control. 

Results: The effectiveness of this radiobiological module is demonstrated by 

applying it to head & neck and prostate cancer cases. The step of selecting 

the prescribed dose level is made by a renormalization of the dose plan until 

P+ is maximized. The results of the radiobiological evaluation are compared 

against dosimetric criteria. A more conformal dose delivery to the target indicates 

a higher control rate for the same complication level. Dose-response 

parameters derived by a maximum likelihood fitting were used as a reference 

to evaluate their compatibility with the examined treatment methodologies. 

Conclusions: The presented tool appears to be very convenient and efficient 

for clinical implementation of radiobiological modeling. It can also be 

used for the development of a clinical data and health information database 

for assisting the performance of epidemiological studies and the collaboration 

between different institutions using the same Treatment Planning System 

within research and clinical frameworks. 

1329 poster 

THE CONFORMAL KIDNEYS SPARING PLANNING METHOD TO 

TREAT PANCREATIC CANCER 

Z. Sebestyén 1 , P. Kovács 1 , R. Farkas 1 , S. Bellyei 1 , G. Liposits 1 , A. 

Szigeti 1 , K. Dérczy 2 , Gulybán 3 , O. Ésik 1 , L. Mangel 1 

1 UNIVERSITY OF PECS, Institute of Oncotherapy, Pecs, Hungary 

2 UNIVERSITY OF PECS, Department of Radiology, Pecs, Hungary 

3 B.A.Z. COUNTY HOSPITAL, Institute of Radiotherapy and Clinical Oncology, 

Miskolc, Hungary 

Purpose: When treating pancreatic cancer using the Standard 3D conformal 

planning technique [Dobbs et al.: Practical rad. planning (book), 1999] (ST 

3D-CRT) the kidneys received in average higher dose than their tolerance 

limit. Using IMRT [ M.W. Brown et al., IJROBP 2006;65] the dose to the kidneys 

could be reduced. Our aim was to find a conformal treatment method 

alternatively to IMRT that spares the kidneys. 

Materials: Since 2005 18 patients with Stage II-III, locally advanced unresectable 

pancreatic cancer were treated with combined chemoradiotherapy 

in our Institute. The CT based 3D treatment planning was done with Precise- 

PLAN 2.02/2.03 (Elekta, Atlanta GA, USA) using the ST 3DCRT technique. 

The prescription dose was 45 Gy to the planning target volume (PTV) in 1.8 

Gy fractions. We developed a Conformal KidneyS Sparing (CONKISS) fivefield, 

non-coplanar beam arrangement, that consisted of a left and a right 

wedged beam-pairs and an AP beam inclined in the caudal direction. We 

also developed an algorithm to adjust the proper direction of the wedges in 

the lateral beams. In both techniques only 6 MV photon beams were used. 

We compared the ST plans with the CONKISS plans retrospectively and we 

evaluated the dose homogeneity according to ICRU 50, 62 recommendations 

with the PTV volume receiving 95-107 % of the prescribed dose (V95- 

107%). The Conformity Index (COIN) was counted according to L. Feuvert 

et al [IJROBP 2006;64]. For the organs at risk (OARs) we used the following 

mean dose limits: kidneys < 12 Gy, liver < 25 Gy, small bowel < 30 Gy, and 

spinal cord maximum < 45 Gy. 

Results: The V95-107% homogeneity was 95.4 % (SD: 2.9) for the ST plans 

and for the CONKISS plans it increased to 95.8 % (SD: 2.0). The COIN was 

0.65 (SD: 0.1) vs. 0.64 (SD: 0.1). The dose to the kidneys decreased: left 

kidney 10.7 Gy (SD: 4.3) vs. 7.7 Gy (SD: 3.0), right kidney 11.4 Gy (SD: 5.1) 

vs. 9.2 Gy (SD: 3.9). The changes in the dose to other OARs were clinically 

irrelevant: liver 15.4 Gy (SD: 3.8) vs. 17.9 Gy (SD: 3.5), small bowel 12.2 Gy

(SD: 6.2) vs. 14.6 Gy (SD: 6.4), spinal cord maximum 15.3 Gy (SD: 3.2), vs. 

15.4 Gy (SD: 4.8). 

Conclusions: According to our results the CONKISS method is better reproducible. 

With this new technique the dose to the kidneys could be reduced 

significantly (p=0.021), meanwhile the homogeneity of the PTV became better 

and the conformity remained. So using 3D-CRT the CONKISS method 

can be a good alternative to IMRT. 

1330 poster 

THE IMPORT HIGH PLANNING STUDY: DEFINING DOSE CON- 

STRAINTS AND TREATMENT PLANNING METHODS FOR COMPLEX 

BREAST RADIOTHERAPY 

H. James 1 , L. Ciurlionis 2 , C. Coles 3 , E. Donovan 4 , H. Mayles 5 , Y. Tsang 

2 , N. Twyman 6 , J. R. Yarnold 7 

1 

IPSWICH HOSPITAL, Physics, Ipswich, United Kingdom 

2 

MOUNT VERNON HOSPITAL, Clinical Physics, Northwood Middlesex, 


3 

ADDENBROOKES HOSPITAL, Clinical Oncology, Cambridge, United 

Kingdom 

4 

ROYAL MARSDEN HOSPITAL (SUTTON), Department of Physics, Sutton, 


5 

CLATTERBRIDGE CENTRE FOR ONCOLOGY, Department of Medical 

Physics, Bebington, Merseyside, United Kingdom 

6 

ADDENBROOKES HOSPITAL, Medical Physics, Cambridge, United Kingdom 

7 

ROYAL MARSDEN HOSPITAL, Academic Radiotherapy, Sutton, United 

Kingdom 

Purpose: The novel design of the UK NCRI IMPORT HIGH randomised clinical 

trial aims to deliver a dose gradient across the breast with maximal dose 

centred on the tumour bed. Consequently complex radiotherapy techniques 

are needed to achieve the required sequential and concomitant boost dose 

escalation in the control and test arms. A planning study was undertaken 

to design practical treatment planning methods and define target doses and 

organ at risk (OAR) dose constraints for the trial protocol. 

Materials: Appropriate and realistically achievable dose targets and constraints 

were defined for IMPORT HIGH based on literature review and limited 

testing on representative CT datasets. These were then tested within a 

comprehensive planning study utilising CT datasets from nine patients with 

implanted gold seeds defining their tumour excision cavity. Volumes were 

contoured according to the IMPORT HIGH draft protocol. Treatment plans 

were created for the control arm comprising tangential whole breast fields 

delivering 40Gy in 15 fractions and 3-5 co-planar conformal wedged fields 

delivering a 16Gy in 8 fractions sequential boost. For test arm 2 (delivering 

36Gy in 15 fractions to the whole breast and 40Gy and 53Gy concurrently 

to partial breast and tumour bed volumes), two sets of plans were created 

on each CT dataset, one forward planned and one inverse planned. Dose 

volume histogram analysis assessed target and OAR doses. 

Results: Dose constraints to the contra-lateral breast, lung and heart were 

achieved in all the control and test arm plans. Forward planning for test arm 

2 resulted in lower contra-lateral lung doses compared to inverse planning 

(average V2.5Gy = 0.03% for forward planned and 7.9% for inverse planned). 

Lower and upper target doses were achieved in all cases for both trial arms. 

In comparison with inverse planning, the forward planned method produced 

higher median doses to the partial breast volumes (average 42.4Gy compared 

with 40.4Gy) and lower median doses to the whole breast volumes 

(average 34.5Gy compared with 35.9Gy). 

Conclusions: Target doses and organ at risk dose constraints have been defined 

for IMPORT HIGH and these are achievable with the robust and practical 

radiotherapy treatment planning methods devised. This study has highlighted 

inherent differences in resulting dose distributions from forward and inverse 

planning methods even when applying the same dose targets and constraints. 

1331 poster 

THE INFLUENCE OF THE CALCULATION GRID SIZE ON THE DOSE 

DISTRIBUTION IN HEAD AND NECK IMRT 

T. Piotrowski 1 

1 GREATPOLAND CANCER CENTRE, Medical Physics, Poznan, Poland 

Purpose: The uncertainties associated with grid size affect the calculation 

accuracy of the treatment planning systems, especially if highly sophisticated 

3DCRT and IMRT plans are concerned. Previous studies concentrated 

mostly on technical and physical aspects. The aim of this study is to show the 

influence of different grid size on the physician’s decision during DVH analysis 

of the head and neck IMRT. 

Materials: 20 patients with postoperative larynx cancer were randomly selected. 

For every patient 7-fields IMRT plan including postoperative bed and 

elective neck node irradiated to 50 Gy was generated. Treatment planning 

system (Eclipse), the calculation algorithm, normalization method and constrains 

used during the optimization process to form dose distribution were 

the same for every plan. After optimization, doses were recalculated using 

1.25 mm, 2.5 mm, 5 mm and 10 mm grid sizes. The produced dose distri- 


S 423 

butions in PTV, parotids and spinal cord were compared using dose-volume 

histograms. Especially differences between dose distributions calculated using 

origin grid (1.25 mm) and others were evaluated. Moreover mean dose 

and doses absorbed in 1% and 99% of volume corresponding respectively to 

maximum and minimum dose were analyzed. 

Results: In the PTV, the highest volume differences were observed for a 

doses between 50% (25Gy) and 98% (49Gy) which strictly corresponds with 

results describing minimum dose differences D(V99%) presented in the table. 

The mean volume difference was 0.01% (range from -0.04% to 0.05%), 

0.5% (range from 0.01% to 1.5%) and 1.2% (range from 0.1% to 6.6%) for 

2.5mm, 5mm and 10mm grid sizes, respectively. Spinal cord analysis shows 

dominated volume differences for doses from 45% (22.5Gy) to 75% (37.5Gy) 

which strictly corresponds with maximum dose differences results D(V1%) 

presented in table. The mean volume difference was 0.01% (range from - 

0.09% to 0.07%), -0.4% (range from -2.9% to -0.05%) and -1.6% (range from 

-9.5% to -0.2%) for 2.5mm, 5mm and 10mm grid sizes, respectively.In the 

parotids, volume differences were observed for whole dose range from 0% to 

100%. The mean volume difference was 0.01% (range from -0.2% to 0.3%), 

-0.1% (range from -1% to 0.9%) and -0.5% (range from -3.7% to 2.4%) for 

2.5mm, 5mm and 10mm grid sizes, respectively. 

Conclusions: Differences between dose distributions calculated using 1.25 

mm and 2.5 mm grid sizes were not statistically and clinically significant. For 

other grid sizes (5 mm and 10 mm) dose and volume differences to the 1.25 

mm grid should be included during the dose-volume evaluation and acceptance 

process. 

1332 poster 

TREATMENT OPTIMISATION AND ADAPTATION BASED ON PET 

HYPOXIA 

I. L. Dasu 1 , A. Dasu 2 , J. Uhrdin 3 , A. Brahme 1 

1 



2 

NORRLAND UNIVERSITY HOSPITAL, Department of Radiation Physics, 

Umeå, Sweden 

3 

RAYSEARCH LABORATORIES AB, Stockholm, Sweden 

Purpose: Hypoxia is one of the most important factors that influence the response 

to radiation treatment. Clinical imaging of tumour oxygenation with 

PET is now possible with several markers and the information thus gathered 

could be used to target the potentially troublesome hypoxic foci. This study 

proposes a method to optimize treatment plans based on the conversion of 

PET hypoxia images into radiosensitivity maps from the uptake properties of 

the tracers used. The method accounts for temporal variations of the oxygenation 

that may influence the treatment outcome. 

Materials: PET hypoxia images obtained with various markers were simulated 

for tumours with heterogeneous oxygenations and then used to calculate 

optimal dose distributions needed to counteract the effect of hypoxic radioresistance. 

A mathematical model has been developed to take into consideration 

the heterogeneity of hypoxia as well as the temporal variations of the 

oxygenation. The efficiency of the biological optimisation approach has been 

evaluated in terms of predicted treatment outcome for fractionated schedules. 

Results: The results have shown that the prescribed doses have to take into 

consideration both the hypoxic distributions given by the PET images and the 

dynamics of hypoxia that could otherwise lead to considerable loss of local 

control. These findings have been incorporated into an algorithm to calculate 

dose distributions from PET images of tumour hypoxia using the relationship 

between the uptake of the marker used and the local oxygen tension. The

S 424 PHYSICS AND TECHNOLOGY : OTHERS 

resulting algorithms for dose prescription have been implemented into an advanced 

treatment planning system and subsequently used for dose planning 

purposes. 

Conclusions: The results have shown that individualisation of the treatment 

based on PET imaging of tumour hypoxia could lead to improved treatment 

outcome by increasing the local control with dose distributions that allow the 

sparing of the surrounding normal tissues. Hypoxia dynamics in particular 

has to be taken into consideration for the optimisation of the treatment plans 

and for the evaluation of the treatment response. 

1333 poster 

TREATMENT PLAN OPTIMIZATION USING DIFFERENT METHODS 

OF DOSE INHOMOGENEITY REGULARIZATION 

G. Komisopoulos 1 , P. Mavroidis 2 , N. Papanikolaou 3 , B. Lind 2 

1 

LARISSA UNIVERSITY HOSPITAL, Department of Medical Physics, Larissa, 

Greece 

2 



3 



Purpose: Today, different methods have been proposed to regularize the 

highly inhomogeneous dose distributions produced by different IMRT treatment 

planning optimization algorithms for determining the optimal dose distribution. 

In the present work, three different uniformity regularization methods 

for optimization of IMRT treatment plans are examined in order to study the 

relation between the dose inhomogeneity in the PTV and the dose fall-off 

towards adjacent normal tissues. 

Materials: Two typical cases of head & neck and prostate cancer treated 

with IMRT were studied. The organs at risk are the normal tissue stroma, 

left parotid gland and spinal cord for the head-and-neck case and the normal 

tissue stroma, bladder and rectum for the prostate case. Three different 

dose distributions were obtained by using a dose-based optimization technique, 

an EUD-based optimization without regularizing non-uniformity and 

an EUD-based optimization using a variational non-uniformity regularization 

technique. The clinical effectiveness of the three dose distributions was investigated 

by calculating the response probabilities of the targets and organs 

at risk together with the complication-free tumor control probability, P+ and 

the biologically effective uniform dose (BEUD). 

Results: In the head & neck cancer case, for the dose-based optimization the 

P+ value is 32.9% and the BEUDPTV is 72.4Gy. The total control probability 

PB is 79.6% and the total complication probability PI is 49.0%. Similarly, for 

the EUD-based no reg optimization, the P+ value is 56.4%, the PB value is 

71.9% and the PI value is 15.5%. Finally, for the EUD-based reg optimization, 

the P+ value is 67.3%, the PB value is 87.4% and the PI value is 20.1%. In 

the prostate cancer case, for the dose-based optimization the P+ value is 

94.8% and the BEUDPTV is 78.2Gy (see figure). The PB value is 97.8% and 

the PI value is 3.0%. Similarly, for the EUD-based no reg optimization, the 

P+ value is 86.0%, the PB value is 97.3% and the PI value is 11.3%. Finally, 

for the EUD-based reg optimization, the P+ value is 95.3%, the PB value is 

98.4% and the PI value is 3.1%. 

Conclusions: In both clinical cases, the radiobiological comparison shows 

that the EUD-based optimization with non-uniformity regularization gives better 

results than the EUD-based optimization without regularization and dosebased 

optimization, which is expected to improve the effectiveness of the 

optimized IMRT dose distributions. 

1334 poster 

TREATMENT PLANNING OF BREATHING ADAPTED RADIOTHER- 

APY BREAST CANCER PATIENTS: IMPLEMENTATION AND INITIAL 

EVALUATIONS OF THE DOSE TO ORGANS AT RISK 

M. Hedetoft 1 , C. Thornberg 1 , L. Ekberg 2 , T. Landberg 2 , S. Ceberg 3 , H. 

Gustavsson 1 , L. Wittgren 1 , S. Bäck 1 

1 

MALMÖ UNIVERSITY HOSPITAL, Department of Radiation Physics, Malmö, 

Sweden 

2 

MALMÖ UNIVERSITY HOSPITAL, Oncology, Malmö, Sweden 

3 

LUND UNIVERSITY HOSPITAL, Department of Medical Radiation Physics, 

Lund, Sweden 

Purpose: In radiation therapy planning the patient movement during respiration 

means that increased margins of the planning target volume (PTV) are 

needed. Accordingly, an increased volume of normal tissue/organs at risk 

(OAR) is also irradiated. Respiratory gating is a breathing adapted radiotherapy 

method that allows radiation beam-on only when the distance between 

the PTV and the OARs is maximized. The aim of this study was to investigate 

and optimise the treatment planning process when introducing this new 

technique. Further, the potential gain for the patient defined as differences 

in planned absorbed doses and irradiated volumes of lung and heart was 

quantified on an individual basis. 

Materials: All fifteen cases included in the study were left-sided ca mammae 

patients that had undergone breast conservation surgery. To validate the implementation 

of respiratory gating, the patients were CT-scanned using both 

prospective respiratory gating and during free respiration. The CT-studies 

were acquired at the same occasion using the same fixation and positioning. 

The slice thickness was 0.3 cm in the respiratory-gated scan and 0.5 cm in 

the free respiration scan. The PTV and OARs i.e. lung, heart and left anterior 

coronary artery (LACA) were identified and delineated by an oncologist 

in both CT-studies. The treatment plans were then constructed and optimised 

by the RTT/oncology nurse using a 3D-treatment planning system (TPS, Masterplan 

v1.5, Nucletron). A standard tangential technique with two opposing 

beams was used. The restrictions defined in the national guidelines for breast 

cancer radiotherapy were followed. This include a maximal distance of one 

cm heart tissue in the treatment field while ensuring the best possible coverage 

of the planning target volume. An oncologist and a physicist approved the 

final treatment plans. From the resulting dose volume histograms the relative 

left lung volume receiving more than 20 Gy (V20Gy), the maximum dose to 

the LACA and the average heart dose were calculated for both the gated and 

non-gated studies. 

Results: During the planning procedure approximately the same amount of 

time was needed to optimise and calculate the gated plans compared with the 

non-gated cases. The average of the V20Gy value was not reduced using the 

gated technique. However, for a number of patients there was a reduction in 

V20Gy of up to 50%. The largest gain was observed for the heart, with a 

reduction of the average dose of 39%, and the LACA, where the average 

maximum dose was reduced by 53% using the gated technique. 

Conclusions: The introduction of respiratory gating had little impact on radiotherapy 

treatment planning workload. The decreased irradiation of OAR volumes 

demonstrated the potential gain for the individual patients in this study. 

Fewer side effects, early as well as lately appearing, can thus be expected. 

Physics and technology : Others 

1335 poster 

A PRELIMINARY STUDY ON PHOTONEUTRON SHIELDING OPTI- 

MIZATION IN A MEDICAL ACCELERATOR ROOM BY USING MONTE 

CARLO SIMULATION 

Y. N. Kim 1 , K. Jeong 1 , C. G. Lee 1 , I. J. Lee 1 , J. Seong 1 

1 YONSEI UNIVERSITY MEDICAL CENTER, Radiation Oncology, Seodaemun- 

Gu, Korea Republic of 

Purpose: Medical linear accelerators (LINACs) operating above 10 MV require 

door shielding for neutrons in addition to photons. A criterion for choice 

of optimal configuration of lamination of BPE (Borated Polyethylene) and lead 

is not clear. Moreover, optimal configuration cannot be determined by the 

conventional method using an analytical formula and simple measurement. 

This study performs Monte Carlo simulation of radiation field in a commercial 

LINAC room. 

Materials: This study employs Monte Carlo simulation in order to evaluate an 

effect of laminating multiple components with various configurations through a 

full transport calculation. Considering two cases of laminating for door shielding 

such as ’lead-BPE’ and ’lead-BPE-lead’, dose attenuations are compared 

with each other. The case of ’lead alone’ is additionally considered and compared 

with both laminations in order to assess the improvement of neutron 

dose attenuation by additional insertion of BPE and its effect on the photon 

dose attenuation. The geometrical dimension of the LIANC room is based on

the treatment room of National Cancer Center, in which a commercial medical 

LINAC, Varian CLINAC 2100C/2300C was set up. 

Results: The obtained results are listed at Table 1 and can be summarized 

as follows:- An additional laminating BPE with lead assists to enhance attenuation 

of neutron dose. However, as far as photon dose attenuation is 

concerned, additional BPE can not give any contribution to photon shielding. 

- When we consider comparing between the configurations of laminations, 

lead-BPE is more effective than lead-BPE-lead for photon dose attenuation, 

whereas they have no difference in neutron dose attenuation. - We should 

also note that the absolute values of neutron doses are much greater than 

those of photon doses outside as well as inside the door by three orders of 

magnitude. 

Conclusions: Based on the results, it is concluded that there is no significant 

difference in effectiveness for door shielding in terms of total dose equivalent 

between lead-BPE-lead and lead-BPE. We, however, propose the latter as 

the optimal configuration from the standpoint of simplicity in fabrication and 

handling. 

1336 poster 

ANALYSIS OF OUT OF FIELD SCATTER DOSE AS A FUNCTION OF 

DEPTH, OFF AXIS DISTANCE, BEAM MODULATION, AND BEAM 

ENERGY AS IT RELATES TO BREAST IRRADIATION 

S. Rodriguez 1 , C. Esquivel 1 , R. Crownover 1 , N. Papanikolaou 1 


Purpose: To characterize scatter dose, as a function of depth and off-axis 

distance, outside the field, using a breast treatment technique for 6 and 18MV 

photon beams. 

Materials: A 30x30x30 solid water phantom was utilized to simulate dose delivery 

to a right ipsilateral breast and the scatter that the contralateral breast 

receives. Both surface dose measurements and planar dose distributions at 1 

and 2 cm depths were analyzed, as well as dose distributions along the transverse 

axis of the phantom perpendicular to the beam. Data was taken using 

EDR2 film, thermoluminescent detectors (TLDs), and Thomson-Nielsen 

MOSFET detectors. A Varian 2100CD linear accelerator was employed to 

deliver 250 MU at a machine dose rate of 600 cGy/min. Measurements were 

performed for two energies for the following plans that are commonly used 

in breast treatments: open field (8x18cm2), 30o and 45o physical wedge, 

30o and 45o Enhanced Dynamic Wedge (EDW), and forward planned (useroptimized) 

IMRT plan using control points. Measurements were repeated 

with the beam in an oblique incidence for a more realistic beam geometry of 

breast irradiation. 

Results: Analysis of the data shows that the surface dose outside the field 

receives significantly higher scatter when physical wedges are used at 18 MV 

energies. For all plans using 18 MV, the out of field scatter at the surface, 1 

cm, and 2 cm depths are higher than those using 6 MV. For 6 and 18 MV, the 

treatment plans using dynamic wedges and control points are comparable to 

those made with an open field and receive relatively the same scattered dose 

at 1 and 2 cm depths. 

Conclusions: This study indicates that out of field scatter depends on beam 

energy, depth of treatment, and treatment modality. It is possible to characterize 

these dependencies through an analytical formalism. The use of EDW 

and forward planned IMRT produced homogenous dose distribution to the 

target breast, with minimum (< 2%) increase in the scatter dose outside the 

field, independent of the energy selection. 

PHYSICS AND TECHNOLOGY : OTHERS 

1337 poster 

S 425 

ASSOCIATION OF DOSE-MASS-HISTOGRAM (DMH) WITH THE 

EXPECTED LUNG COMPLICATIONS FROM BREAST CANCER 

RADIOTHERAPY 

G. Plataniotis 1 , M. Adamus-Górka 2 , S. Hyödynmaa 3 , N. Papanikolaou 4 , 

B. Lind 2 , P. Mavroidis 2 

1 

ABERDEEN ROYAL INFIRMARY, Department of Radiotherapy, Aberdeen, 


2 

KAROLINSKA INSTITUTET AND STOCKHOLM UNIVERSITY, Department of 


3 

TAMPERE UNIVERSITY HOSPITAL, Department of Oncology, Tampere, 

Finland 

4 



Purpose: Lung is the main dose limiting tissue in breast cancer radiotherapy 

usually lying within the irradiated volume. Consequently, the estimation of expected 

lung complications is very important in treatment optimization. In this 

study, it is investigated whether lung complications are better associated with 

the dose-mass-histogram (DMH) concept than the dose-volume-histogram 

(DVH) concept. 

Materials: First, two hypothetical dose distributions (Gaussian and Semi- 

Gaussian shaped) were applied on two lungs of uniform and varying densities 

to perform a theoretical analysis. Then, for a clinical quantification of 

the difference between DVH and DMH, a group of breast cancer patients 

was used. These patients were treated with resection (negative node involvement) 

and irradiation with two tangential fields. The clinical endpoint of 

radiation induced pneumonitis was used to estimate the deviation between 

DVH and DMH. For this purpose, the Relative Seriality and LKB models with 

the respective Gagliardi et al 2000 and Seppenwoolde et al 2003 parameter 

sets, were used. The biological equivalent of the dosimetric differences was 

estimated by the biologically effective uniform dose (BEUD) and Equivalent 

Uniform Dose (EUD) concepts, respectively. 

Results: The range of the deviation between the DVH and DMH is large in 

terms of expected clinical outcome. In the theoretical and clinical studies it is 

shown that the relation of the DVH and DMH varies depending on the applied 

dose distribution and the underlying cell density distribution. According to the 

patient DVHs, lung receives 9.82 Gy, whereas according to the corresponding 

DMHs it receives 8.06 Gy (1.76 Gy difference). In terms of lung response, 

DVH gives 0.30% probability for lung complications compared to 0.10% given 

by DMH for the Relative Seriality model. Similarly, for the LKB model the 

corresponding values are 2.62% and 1.85%, respectively. It is shown that 

the impact of the DVH variation from the patient positioning and breathing 

uncertainties is of the same order with that of the deviation between the mean 

values of the DVH and DMH. The results of the comparison between DVH and 

DMH using the LKB model are shown in the Table. 

Conclusions: The effectiveness of the dose distribution seems to be closer 

related to the lung complications when using the DMH rather than the DVH 

concept. Furthermore, the expected lung complications appear to be overestimated 

when using the DVH concept.

S 426 PHYSICS AND TECHNOLOGY : OTHERS 

1338 poster 

DETERMINATION OF PERIPHERAL FROM DYNAMIC MLC IMRT 

FOR 6 MV AND 18 MV BEAM ENERGIES 

A. Sanchez-Reyes Fernandez 1 , N. López Vilanova 2 , A. Vila 3 , M. A. Duch 

2 1 1 3 2 

, A. Rodriguez Garcia , S. Loscos , L. M. Moya , M. Ginjaume , A. 

Pedro 1 

1 


2 

UPC, INTE, Barcelona, Spain 

3 

HOSPITAL PLATO, Radioterapia, Barcelona, Spain 

Purpose: Determination of peripheral doses from the delivery of 6 MV an 18 

MV intensity modulated radiation therapy (IMR) and conventional (3DCRT) in 

some different real treatments (prostate, breast, head and neck, brain cancer). 

Comparison between 6 MV and 18 MV IMRT treatments and 3DCRT 

treatments. 

Materials: Peripheral doses (PD) from uniform dynamic multileaf collimation 

fields were measured for 6 MV and 18 MV on a Varian 2100 CD 120 Millenium 

MLC using TLD dosimeters inserted into a RANDO Anderson anthropomorphic 

phantom. PD measurements were carried out under identical conditions 

for 4 prostate patients (6 and 18 MV), 4 head and neck patients ( 6MV), 1 

breast patient (6 MV), 1 hypophysis patient (6 and 18 MV) and 1 glioma patient 

(6 and 18 MV). The measured PD from these patients were compared 

with the corresponding data from uniform fields (3DCRT treatment) having 

similar jaws setting. Dosimetric planning was carried out using ECLIPSE 

Varian and HELIOS IMRT module. No effective doses of secondary neutron 

produced by 18 MV photon fields were taken into account in this communication. 

Results: The measured peripheral dose per monitor unit (PD/UM) decreases 

almost exponentially for both static field and IMRT field regardless of energy 

(6 or 18 MV). We also found that PD per UM are very similar regardless the 

type of field, IMRT or static, as well as the energy employed. However, the 

difference between UM delivered in a IMRT or 3DCRT treatment implies that 

PD in a 3DCRT treatment are four times lower than those corresponding to 

the equivalent IMRT treatment. 

Conclusions: Our study shows that PD data generated by dynamic multileaf 

and uniform fields can be used to estimate the out of field critical organ 

in real patients treated with different radiotherapy treatments.This work was 

supported in part by a grant FIS PI06/0394 

1339 poster 

DIAGNOSING LINAC’S MECHANICAL MALFUNCTION AND 

THE VERIFICATION OF REPAIRS WITH MODEL BASED (EPID) 

WINSTON-LUTZ TEST 

A. Kulmala 1 , A. Kangasmäki 1 , M. Tenhunen 1 

1 HELSINKI UNIVERSITY CENTRAL HOSPITAL, Helsinki, Finland 

Purpose: In this work, a suspected mechanical failure of a linac was investigated 

and explanation of cause of abnormal radiation isocentre movements 

was pursued. The test was repeated after repairs to verify the successful 

corrections. 

Materials: This study was carried out with linac equipped with amorphous silicon 

electronic portal imaging unit. A model based WinstonLutz test was used 

to monitor the position of radiation field centre relative to the laser-pointed 

isocentre, marked with tungsten sphere. A 20 mm conical collimator attached 

to linac’s upper wedge mount. The Winston-Lutz test was performed for i) 

collimator rotation at 0 and 90 gantry angles and for ii) gantry rotation with 0 

and 90 collimator angles. The gantry rotation test with 0 collimator angle was 

performed both clockwise and counter clockwise directions. All tests were 

repeated after repairs. 

Results: The exact nature of the analysis combined with graphical presentation 

made the identification abnormal behaviour of the linac even more 

evident than using only numerical analysis. In the collimator rotation test, 

deviation from the predicted circular trajectory at 0 gantry angle was normal 

(SD=0.05mm, max=0.14mm), but abnormal at 90 gantry angle (SD=0.19mm, 

max=0.45mm). In the gantry rotation test with 0 collimator angle, the lateral 

deviation from the sinogram was noticeable (SD=0.43mm, max=0.62mm). 

The longitudinal deviation from the usual sagging curve was also present. 

The gantry rotation test at 90 collimator angle revealed that the direction of 

larger deviation also turned 90. Furthermore, the observed irregularities depended 

on the gantry rotation direction. These findings led us to the conclusion 

that the collimator bearing was defective. Five of six screws holding 

the lower portion of collimator were found to be loose and one screw had 

opened by a few millimeters. In the repairs, the bearing was replaced and the 

collimator screws were tightened. All irregularities of the radiation isocentre 

movements disappeared after repairs, typical deviation in all repeated tests 

being SD=0.04mm and max=0.10mm. 

Conclusions: The presence of a mechanical failure, such as in the present 

case, can also be found using traditional QA tests. But with these tests it 

is impossible to characterise and quantify the findings. The model based 

Winston-Lutz test was found to be quantitative and informative in diagnosing 

the mechanical failure and verifying successful repairs. 

1340 poster 

DOSIMETRIC CHARACTERIZATION OF 6 MEV ELECTRON FIELDS 

SCATTERED BY MEANS OF ALUMINIUM FOILS FOR SMALL 

SURFACE SKIN DISEASES 

A. Rodriguez Garcia 1 , A. Sanchez-Reyes 1 , S. Loscos 1 , A. Vila 2 , C. 

Lainez 2 , L. M. Moya 2 , N. Artola 2 , J. C. Julia 2 , A. Pedro 1 

1 HOSPITAL PLATO, Unidad Radiofisica, Barcelona, Spain 

2 HOSPITAL PLATO, Radioterapia, Barcelona, Spain 

Purpose: The dosimetric characterization of 6 MeV electron fields degenerated 

by means of Aluminium (Al) foils to achieve the required energy to 

irradiate surface skin diseases (epitheliomas, keloids&) with a Rp of 20 mm 

to preserve the deep tissues. 

Materials: The nominal 6 MeV energy electron fields generated by a CLINAC 

2100 CD have been modified and degenerated by placing Al foils of different 

thicknesses on the electron applicator to achieve a Ep0 between 5.97 MeV 

(Nominal) and 4.22 MeV (4 mm Al). Depth doses and profiles for different 

electron applicators (from 6x6 up to 20x20) have been measured by means 

of a RFA 300 water phantom with semiconductor detectors. Absolute doses 

were determined using an electron Ross ionization chamber following the 

IAEA TRS-398 protocol. A geometrical simple Montecarlo simulation using 

the PENELOPE Code has also been calculated. 

Results: The following figure shows the depth doses for a 6 MeV nominal 

field and a 4 mm Al foil degenerated field as well as the Montecarlo calculations. 

It can be observed a very good correlation between measured and 

calculated data. The obtained parameters for 6 MeV + 4 mm Al foil were: 

R100 = 6 mm, R90= 8 mm, R50= 14.5 mm, Rp = 20 mm, Ep0= 4.22 MeV 

and E0= 3.37 MeV. In this communication, we also present the lateral profiles 

for different depths to determine the effective irradiation volume. More of 

15 patients have been treated so far with this technique without subsequent 

complications. 

Conclusions: 6 MeV electron degenerated fields by using Al foils placed on 

the electron applicator could be a good technique to irradiate superficial tumors 

(less than 1 cm depth) without significant dose in the depth tissues.This 

work was supported in part by a grant FIS PI06/0394

1341 poster 

EXPERIENCE WITH HDR VALENCIA SKIN APPLICATORS COMMIS- 

SIONING PROCEDURE 

Z. Ouhib 1 , J. Perez-Calatayud 2 , D. Granero 2 , F. Ballester 3 , E. Colla 4 , J. 

Richart 5 , V. Gonzalez 2 , M. Pujades 2 

1 

BOCA RATÓN COMMUNITY HOSPITAL, Lynn Cancer Institute, Boca Ratón, 

USA 

2 


3 



4 

NUCLETRON, Veenendal, Netherlands 

5 

CLINICA BENIDORM HOSPITAL, Radiotherapy Department, Benidorm, 

Spain 

Purpose: The Valencia applicators are accessories of the microSelectron 

HDR (Nucletron, Veenendaal, The Netherlands) dedicated to skin treatments. 

These applicators are tungsten cup shaped provided with a flattering filter to 

homogenize laterally the dose distribution, designed for superficial treatments 

of lesions up to 3 cm in diameter 3-4 m in depth. The aim of this presentation 

is the proposition of a set of test for the Commissioning of these applicators 

derived from the experience with 4 sets. 

Materials: The Commissioning procedure should involve the following aspects: 

(1) Manufacturer documentation, integrity and physical verification: include 

the tube length introduced in the cup, which will be responsible of the 

used source to indexer distance (SID). (2) Centering: to obtain the SID of the 

vertex of the cone. In the practice, the use of a well chamber is not suitable, 

it is bether the use of radichromic film, where small deviations from the right 

position have clear influence in the flatness. Typical values are 1321 mm (v2) 

and 815 (classic). (3) Flatness at 3 mm, usually done with radiochromic film. 

(4) Output verification: cGy/(h U) at 3 mm depth on axis, named OF. It can 

be done with a well chamber plus specific insert measuring the Corresponding 

Factor (CF) and comparing it with the reference values [Granero MPH 

2008] The previous test can be complemented with ionization chamber measurements 

on solid phantoms. Due to the high gradient (10% per mm depth) 

efective point should be considered in clindrical chamber; small volume or 

paralell plate chamber could be used; in the former case the active diameter 

must be kept into the useful beam. Usually calibration from Cobalt can be 

used without correction factors. (5) Treatment planning datasets: PDD and 

off-axis profiles from Monte Carlo experimentally verified method, available 

on www.uv.es/braphyqs (6) Treatment plan for each patient. A library plan 

can be created on the PLATO TPS with just 1 dwell position; a dose point 

is introduced along the transversal source axis in which the dose rate is the 

same that the OF; with distances are 22.394 and 26.065 mm for the 2 and 3 

cm Valencia respectively. For depth different from 3 mm, F factor existing in 

TPS PLATO (Nucletron) could be used. (7) QA for each treatment plan: With 

a spreadsheet, source decay is independently calculated to check the console 

time during fractions. Independent calculations are done with OF and 

PDD from tables using the actual SK. Caution with identification of 2 cm and 

3 cm applicators is very important due the 35% output difference. 

Results: The described commissioning procedure is adequate in the clinical 

implementation of these new applicators. Library plans created on the TPS 

plus QA procedure have been proposed. 

Conclusions: The Valencia applicators are accessories on the MicroSelectron 

HDR being their described commissioning and clinical implementation 

fast and complete. 

1342 poster 

FAST AUTOMATED MONITORING AND ACHIEVABLE ACCURACY 

OF AN ELEKTA BEAM MODULATOR 

A. van der Borden 1 , H. Meertens 1 , P. van der Hulst 1 , P. Crol 1 , H. 


1 UNIVERSITY MEDICAL CENTRE GRONINGEN, Department of Radiation 


Purpose: IMRT treatments require a significantly higher demand on leaf positioning 

than conventional treatments. Therefore, an accurate, fast and reproducible 

quality assurance (QA) method is required to monitor leaf position. 

The aim of this study was to assess what accuracy can be achieved during 

monitoring of the Elekta Beam Modulator (BM) with reasonable efforts using 

an automated procedure. 

Materials: The Elekta AutoCAL version 2.0 was used for BM calibration. The 

software uses acquired EPID images of five 2x16 cm2 fields with a spacing of 

2 cm between each pair of adjacent fields. These images were analysed by 

comparing the actual position of each individual leaf from both leaf banks (Y1/ 

40 leafs and Y2/ 40 leafs) to its expected position. A linear function is then 

derived by AutoCAL from the calculated positioning errors. From this function, 

the gain and offset were calculated for each individual leaf. Additional images 

were taken for EPID orientation, to reconstruct the radiation centre and to 

calibrate the pixel size needed for calculation of the actual dimensions at isocentre. 

Results: The short term reproducibility (same day) of the leaf banks was 

within 0.1 mm (SEM). An average shift of the leaf banks was found of

S 428 PHYSICS AND TECHNOLOGY : PATIENT IMMOBILIZATION/POSITIONING 

Conclusions: Pattern recognition methods coupled with 1H MRS revealed 

significant treatment-dependent alterations in normal-appearing cerebellar 

tissue as well as metabolic changes induced by tumor progression/recurrence. 

1345 poster 

RADIOTHERAPY AND PACEMAKERS / IMPLANTABLE 

CARDIOVERTER-DEFIBRILLATORS: PRACTICAL GUIDELINE 

AND DOSE ASSESSMENTS 

P. van der Hulst 1 , A. van der Borden 1 , A. Maass 2 , F. Ubbels 1 , H. Mulder 

2 , P. Stellingwerf 2 , I. van Gelder 2 , H. Langendijk 1 , A. van ’t Veld 1 




Department of Cardiology Thoraxcenter, Groningen, Netherlands 

Purpose: Presentation of a practical guideline for precautions for radiotherapy 

(RT) patients with a pacemaker (PM) or implantable cardioverterdefibrillator 

(ICD) and associated evaluation of PM/ICD doses. 

Materials: Practical guideline: Our previous guideline (2004) did not include 

recent publications on the influence of RT on ICDs. Therefore an update 

was undertaken to include precautions for patients with an ICD (2008) and 

a flow chart as a risk-based decision tool was developed. In the guideline 

the threshold dose for precautionary measures was lowered from 2.0 to 0.5 

Gy (PMB 2002,47,2879-2893).ICD monitoring and on/off switching- a risk assessment: 

PM/ICDs have an associated risk of malfunction and failure. The 

malfunction replacement rate for ICDs is significantly higher than that for PMs 

(JAMA 2006,295,1901-1906). Although RT is one of the known risk contributors, 

data about RT and ICDs is still scarce. Based on publication and 

expert opinions the risks of alternative procedures were weighed. A known 

risk factor is delivery of a shock due to electromagnetic interference (EMI). 

Therefore in development of our guideline it was first decided that a cardio 

technologist (CAT) switched all ICDs to "monitor only" mode during every RT 

fraction at the RT department and to return to therapy mode immediately after. 

However, balancing this risk to the risk that the patient actually needs the 

therapy function of the ICD during RT, the latter is estimated to be more important 

than the EMI-induced shock. Thus in the final guideline ICDs are not 

switched off anymore.PM/ICD dose assessments: In the period 2004-2007 

a total number of 27 PM/ICD total dose assessments have been performed 

(18 & 9 respectively). Dose assessment is only indicated for cases where 

the PM/ICD is within 20 cm of the nearest field border because the dose to 

the PM/ICD was determined to be well below 0.5 Gy otherwise. The dose to 

the PM and ICD is estimated using a) treatment planning system (Helax TMS 

or Pinnacle) using the average & max dose, b) Peridose (R&O,2001,58,209- 

213), c) tabulated data or d) TLD-measurement. In most cases a combination 

of a) and b) is used. 

Results: ICD monitoring and on/off switching: In the period 2004-2007 all 9 

ICDs were switched off to "monitor only" and monitored during the RT fraction 

by a CAT. After finalization of the guideline (March 2008) this precaution 

was considered not appropriate anymore and only for a selected group of patients 

a weekly ICD/PM check remains. As a result, this significantly reduces 

workload for a CAT. 

Conclusions: 

1. A PM/ICD guideline based on recent publications has been implemented 

in our department. 

2. ICDs are better not to be switched off to "monitor-only" during every 

RT fraction. 

3. For 16/27 patient’s precautions were necessary using a dose threshold 

of 0.5 Gy. 

Physics and technology : Patient 

immobilization/Positioning 

1346 poster 

THE QUALITY ASSURANCE IN CRANIOSPINAL IRRADIATION IN 

THE SUPINE POSITION 

K. Ficek 1 , S. Bacia 2 , S. Blamek 1 , M. Leszek 1 , K. Slosarek 2 

1 CENTER OF ONCOLOGY, Department of Radiotherapy, Gliwice, Poland 

2 CENTER OF ONCOLOGY, Department of Treatment Planning, Gliwice, 

Poland 

Purpose: Craniospinal irradiation for children with medulloblastoma is very 

important technique in pediatric radiotherapy. Treatment in supine position is 

save and comfortable and preferable for children requiring anaesthesia. The 

aim of our study was to present clinical experiences with the quality assurance 

procedures using in this technique. 

Materials: The termoplastic mask is used for patient immobilisation. The 

mask was done by using 2 parts head and trunk mask. Treatment planning 

and dose calculation was performed on 3D planning system. The children 

were irradiated using two separate isocentres for the cranial fields and 

spinal field. For fields verification were used daily digital photographs based 

on skeletal structures(kV).Field placement errors of greater than 1 mm was 

identified and corrected before treatment.We performed dosimetry in vivo to 

access prescribe dose. 

Results: All digital photographs in 3 axis (XYZ) were analysed. The movement 

of patients were minimal from 0 to 5 mm ( median 3 mm). 

Conclusions: The supine craniospinal position is precise and reproductable. 

The daily verification based on digital photographs is simple and timespraying. 

Our procedures of QA coul be recommended for pediatric patients. 

1347 poster 

A FRAMELESS FIXATION SYSTEM FOR LINAC BASED INTRACRA- 

NIAL RADIOSURGERY HAS SUPERIOR POSITIONING ACCURACY 

COMPARED WITH THE ESTABLISHED INVASIVE FRAME SYSTEM 

E. Blokzijl 1 , M. Hollander 1 , R. Bolt 1 , A. Borden van der 1 , H. Langendijk 

1 , H. Bijl 1 

1 UNIVERSITY MEDICAL CENTER GRONINGEN, Department of Radiation 


Purpose: The invasive frame is the golden standard for optimal fixation in 

linac based stereotactic radiosurgery. This system is well established but 

has some disadvantages such as patient discomfort and lack of logistical 

flexibility. With the introduction of the frameless mask system in combination 

with a robotic table and the ExacTrac (ET) verification system (Brainlab), the 

question was posed as to whether this new approach could be a reliable 

alternative for the invasive frame, in particular with respect to the positioning 

accuracy. To answer this question we assessed the positioning accuracy of 

the frameless and invasive frame system. 

Materials: A radiosurgery head phantom was modified with a 12 mm3 air 

cavity, designated as PTV, and which is visible in kV imaging. A CT-scan 

was used to delineate the PTV in iPlan-Image 3.0 (BrainLab). A treatment 

plan consisting of 2 orthogonal beams (6 MV, 18mm2, aligned to the PTV) 

was created in Brainscan 5.31 and the treatment was delivered on a Brainlab 

Novalis linac. The positioning of the invasive head frame was performed 

by aligning the target positioner overlaying the laser lines. Positioning of the 

frameless mask system was executed with the ET 6D Infrared (IR)/X-ray system 

using the bony anatomy of the head phantom. ET (kV) images were 

used to validate the positioning accuracy of the invasive frame-based and 

frameless radiosurgery. To assess the positioning accuracy of the invasive 

frame with the ET system a carbon plate with infrared markers was mounted 

on the frame. To estimate the positioning accuracy in different positions, the 

orthogonal X-ray images were obtained at different table-angles (i.e. 0-90 ◦ , 

0-270 ◦ ), and correction shifts were calculated from the fusion of these images 

to corresponding reference DRR’s. For the frameless mask system, 

these shifts were done under guidance of the IR system. Shifts calculated 

for the invasive head frame are defined as unadjusted deviations since these 

deviation are not adjusted in daily practice. 

Results: The analysis of the ET-data shows that positioning accuracy of the 

frameless system was significantly better compared with the invasive system. 

(table 1)

Conclusions: The frameless fixation system (BrainLab) for radiosurgery has 

a superior positioning accuracy compared with the invasive frame. Considering 

this outstanding positioning accuracy, the patient comfort and the logistical 

flexibility, the frameless system in combination with the robotic table and the 

ET, should be the first choice for head fixation in linac based radiosurgery. 

1348 poster 

A PHANTOM BASED VALIDATION PROCEDURE OF THE POSITION- 

ING ACCURACY OF LINAC BASED FRAMELESS RADIOSURGERY 

VERSUS AN INVASIVE HEAD FRAME 

R. Bolt 1 , A. van der Borden 1 , E. Blokzijl 1 , M. Hollander 1 , H. Bijl 1 , H. 




Purpose: We developed a phantom based procedure to assess the positioning 

accuracy of intracranial Stereotactic RadioSurgery (SRS) based on a 

frameless mask system versus an invasive frame (Brainlab).Aim of our study 

was to validate this procedure and to test the hypothesis that the frameless 

SRS procedure is at least as accurate as the invasive head frame, considered 

as the golden standard. Confirmation of this hypothesis will allow improvement 

of patient comfort and accuracy. 

Materials: An antropomorphic radiosurgery head phantom (CIRS model 605) 

was modified with a 12x12x12 mm 3 air cavity to mimic a ’tumour’, visible in 

both kV and MV imaging. A CT-scan of this ’tumour’ was delineated in Brainlab 

iPlan-Image 3.0. A treatment plan (2 orthogonal beams, 6 MV, 18x18 

mm 2 , aligned to the ’tumour’) was created in Brainscan and delivered on a 

Brainlab Novalis linac.Positioning of the frameless system was done with the 

Exactrac-6D system using the bony anatomy of the phantom. Positioning 

of the invasive system was done in the standard way by aligning target positioner 

overlays to the room lasers.Exactrac (kV) and Gafchromic EBT film 

(MV) images were used to assess positioning accuracy in frame-based and 

frameless SRS. In the invasive frame, a carbon plate with infrared markers 

was mounted to assess positioning accuracy with the Exactrac system. 

Results: The modified phantom allows assessment of positioning accuracy 

both with kV and MV imaging. The Exactrac system verified the positioning 

with an accuracy of 0.5 mm. A film based procedure using 6 MV treatment 

beams as an independent means to verify positioning accuracy showed the 

highest spatial resolution (< 0.3 mm).MV-film analysis showed an average 

positioning accuracy for different table angles of 0.9 ± 0.2 mm (1 SD) for 

the frameless procedure and 0.9 ± 0.1 mm for the invasive SRS system. 

This confirms our hypothesis that a frameless SRS procedure is at least as 

accurate as the established invasive frame procedure. 

Conclusions: Our phantom procedure is well suited to verify positioning 

accuracy in linac based SRS. While the Exactrac system has an accuracy 

that suffices well in clinical practice, the highest accuracy was found in a 

film based procedure. Our results confirm our hypothesis that the frameless 

procedure is at least as accurate as the golden standard (invasive frame) procedure.Considering 

the outstanding positioning accuracy and patient comfort, 

the frameless system should be the first choice for head fixation in linac based 

radiosurgery. 

1349 poster 

A RETROSPECTIVE STUDY OF THE DAILY SETUP ERROR FOR 


W. Crijns 1 , J. Hrbacek 1 , Y. Lievens 1 , J. Verstraete 1 , F. Van den Heuvel 1 

1 UNIVERSITY HOSPITAL LEUVEN, Department of Radiotherapy, Leuven, 

Belgium 

Purpose: This work presents a retrospective study of the daily setup error for 

lung cancer patients. 

Materials: Manual rigid matching of portal images on DRRs was done, using 

matching structures, during the first three treatment sessions. 407 matches 

from 62 patients were evaluated. The data consists of matching result deviations 

in caudal-cranial (CC), posterior-anterior (PA) and left-right (LR) direc- 

PHYSICS AND TECHNOLOGY : PATIENT IMMOBILIZATION/POSITIONING 

S 429 

tion. Dependency of setup error as function of imaging direction (anterior or 

lateral), gender, and session number is investigated. Yielding in 9 datasets 

for the CC deviations (left, right, anterior imaging direction, male, female, 

session 1-3 and no subdivision), 8 PA datasets (no anterior imaging) and 

6 LR datasets (only anterior imaging), resulting in 23 setup mean and SDvalues. 

For each dataset the Gaussian nature was checked employing the 

K-S method. 

Results: The mean setup error of all 23 datasets is within ±1.2mm. The 

SDs in the LR and AP directions are comparable. CC SDs are slightly 

smaller. Data sets considering left imaging have larger SDs than right imaging 

datasets. Neither male vs. female SD differences nor SD differences 

between sessions were noted for the AP direction. For LR and CC the third 

session dataset resulted in larger SDs. K-S test resulted in low p-values for 

CC Gaussian nature (p


Conclusions: Positioning HNSCC patients with Sinmed Posicast (R) thermoplastic 

masks together with the use of helical tomotherapy MV-CT allows 

to reliably correct systematic errors and to substantially reduce PTV margin 

to be applied to no more than 3.5 mm. 

1351 poster 

ACCURACY OF DIFFERENT MASK SYSTEMS FOR PATIENT 

POSITIONING USING AN ON BOARD CONE BEAM CT 

B. Dobler 1 , M. Hipp 1 , O. Koelbl 1 , M. Riepl 1 , P. Haertl 1 , L. Bogner 1 , F. 

Pohl 1 

1 UNIVERSITY OF REGENSBURG, Department of Radiotherapy, Regensburg, 

Germany 

Purpose: The purpose of the study was to evaluate the accuracy of different 

mask systems for patient positioning in radiation therapy of head and neck 

cancers using an on board cone beam CT. 

Materials: 14 patients treated with radiation therapy (RT) of head and neck 

tumours at an Elekta SynergyS R○linac equipped with a Hexapod R○table top 

and XVI R○cone beam CT (CBCT) were included in the study. Patient fixation 

was performed using a thermoplastic mask system for fractionated RT in 8 

cases, and in 6 cases a rigid mask system for stereotactic treatments was 

used. Patients were setup on the treatment table in the respective mask 

system using room lasers. For verification of the setup, a CBCT was acquired 

and registered with the reference treatment planning CT data set of 2mm slice 

thickness. The required correction values were calculated in 6 degrees of 

freedom (3 translational, 3 rotational) using the XVI software. The correction 

values of 66 registrations were evaluated to assess the accuracy of the two 

mask systems. The accuracy of the positioning process with the XVI system 

has been determined by phantom measurements to be within 1mm in each 

direction. 

Results: The length of the 3-dimensional vector required to correct for the 

translational error according to the XVI system was 3.5mm ± 1.8mm for 

the thermoplastic mask and 3.0mm ± 1.8mm for the stereotactic mask averaged 

over all CBCT corrections. Mean values and standard deviations of the 

latero-medial (Tx), cranio-caudal (Ty), and ventro-dorsal (Tz) components of 

the translation and the rotational corrections around the latero-medial (Rx), 

cranio-caudal (Ry), and ventro-dorsal (Rz) axis are given in table 1. 

Conclusions: The stereotactic mask allows a slightly more accurate patient 

positioning than the thermoplastic mask. For treatments which require a very 

high geometrical accuracy, e.g. stereotactic treatments and IMRT, however, 

the use of an on board CBCT is recommended for accurate patient positioning. 

1352 poster 

ANALYSIS AND MANAGEMENT OF SET-UP UNCERTAINTIES FOR 

HEAD AND NECK CANCER RADIOTHERAPY. INTEROBSERVER 

VARIABILITY. 

C. Munoz Montplet 1 , D. Jurado 1 , J. Vayreda 2 , C. Auñon 2 , S. Pelaez 2 , E. 

Canals 2 , L. Angada 2 

1 

INSTITUT CATALA D’ONCOLOGIA-HOSPITAL DR. JOSEP TRUETA, Medical 

Physics, Girona, Spain 

2 

INSTITUT CATALA D’ONCOLOGIA-HOSPITAL DR. JOSEP TRUETA, Radio- 

therapy, Girona, Spain 

Purpose: The aim of this study was to analyze interobserver variability of setup 

uncertainties for head and neck patients treated in our institution. Several 

correction protocols were studied to minimize systematic errors. Setup margin 

(SMi) in each direction, where i=medial-lateral (ml), cranial-caudal (cc) 

and anterior-posterior (ap), was determined in each case. Time trends were 

also evaluated. 

Materials: 10 arbitrarily chosen head and neck patients were simulated and 

treated in supine position using short face thermoplastic masks and standardsized 

rests attached to a carbon fiber base plate fixed to the table couch. Patients 

were positioned in the treatment unit by alignment of lasers with skin 

tattoos. For each patient, set-up errors (translations d and in-plane rotations 

θ) were measured independently by 2 radiation oncologists using orthogonal 

megavoltage EPID images during the first 5 fractions. Results were compared 

using paired samples t-tests. The impact of first-day correction (FD) 

and no action level (NAL) protocols (n=2,3) with adaptive maximum likelihood 

(AML) was calculated. The expression proposed by Van Herk et al. was then 

used: SMi=2.5Σi+0,7σi where Σi and σi are the standard deviations in each 

direction of systematic and random error respectively for this group. Mean 

systematic errors (µi) were also calculated.We considered that a time-trend 

appeared in subsequent fractions when the displacement in any direction exceeded 

2 times the random set-up error of the considered patient in that direction 

with a threshold value of 3 mm. Follow-up was performed for 8 and 6 

patients after approximately 10 and 20 fractions respectively. 

Results: No statistically significant differences were found between the 2 observers. 

Averaged results are shown in table 1. Margins below 7 mm were 

obtained with FD. Margins below 5 mm were achieved applying NAL2AML. 

No further improvement was obtained by increasing n.Time trends were observed 

in 1 out of 8 and in 5 out of 6 patients after approximately 10 and 20 

fractions respectively, mainly in cc direction. 

Conclusions: Interobserver variations in measuring set-up errors were not 

statistically significant. NAL2AML off-line correction protocol led to margins 

below 5 mm in all directions, which can be considered acceptable in clinical 

practice.Time trends dramatically increased during the second half of the 

treatment period, probably due to anatomical changes. A new planning CT 

may be performed after two or three weeks of treatment in order to account 

for dosimetric variations. 

1353 poster 

ANALYSIS AND MANAGEMENT OF SET-UP UNCERTAINTIES IN 

GYNAECOLOGICAL CANCER RADIOTHERAPY 

D. Jurado Bruggeman 1 , C. Muñoz 1 , J. Marruecos 2 , J. Vayreda 2 , E. 

Canals 2 , L. Anglada 2 

1 

INSTITUT CATALA D’ONCOLOGIA-HOSPITAL DR. JOSEP TRUETA, Medical 

Physics, Girona, Spain 

2 

INSTITUT CATALA D’ONCOLOGIA-HOSPITAL DR. JOSEP TRUETA, Radio- 

therapy, Girona, Spain 

Purpose: The aim of this work was to study set-up uncertainties for the group 

of gynaecological cancer patients treated in our institution. The efficiency of 

several correction protocols was analyzed in order to minimize systematic 

set-up errors and to determine set-up margins (SMi) in each direction, where 

i=medial-lateral (ml), cranial-caudal (cc) and anterior-posterior (ap). Set-up 

time trends were also evaluated. 

Materials: Sixty-one gynaecological cancer patients were arbitrarily chosen. 

Patients were simulated and treated in supine position using knee and feet 

immobilization devices. Patients were positioned by alignment of lasers with 

skin tattoos. For each patient, set-up errors in each direction were measured 

using EPID imaging during the first treatment sessions (from three to nine). 

From these measurements, systematic and random set-up errors were determined 

in each direction for each patient. To characterise our group of patients, 

mean systematic errors (µi) and standard deviations of systematic (Σi) and 

random (σi) errors were determined. Patients with large random set-up errors 

(random vector length>7mm) were excluded from the group as they were 

positioned using an on-line correction protocol.Set-up margin was obtained 

using the expression proposed by Van Herk et al.: SMi=2.5Σi+0.7σi.In order 

to establish our correction strategy for the group, the impact of the following 

correction protocols was simulated by Monte Carlo: first-day correction (FD), 

no action level (NAL) (n=2, 3, 4) and shrinking action level (SAL) (α=9mm; 

nm=2, 3, 4) with and without adaptive maximum likelihood (AML).Set-up time

trends were also evaluated in sessions ten and twenty. We considered that 

a time trend appeared when the measured displacement vector length exceeded 

two times the random set-up error of the patient with a threshold 

value of 5mm. 

Results: Nine patients (15%) had random errors larger than 7mm and were 

excluded from the group. Group parameters and SMi for the most common 

(FD) and for the most efficient (NALn=3AML) correction protocols are shown 

in the table.Set-up time trends were detected for 18% of patients either in 

session ten or twenty. 

Conclusions: Patients with large random errors should be positioned using 

an on-line correction protocol. NALn=3AML off-line correction protocol improves 

patient set-up accuracy so that SMi ranges from 4 to 5 mm. Set-up 

time trends must be evaluated and we propose a criterion based on patient 

random error. 

1354 poster 

ASSESSMENT OF SETUP ERRORS USING THREE DIFFERENT 

IN-ROOM IMAGING SYSTEMS IN TREATMENT OF HEAD AND NECK 

IMRT PATIENTS 

N. Dogan 1 , H. Saleh 1 , E. Weiss 1 , J. Shumadine 1 , S. Song 1 

1 VIRGINIA COMMONWEALTH UNIVERSITY, Radiation Oncology Department, 

Richmond, VA, USA 

Purpose: Improvement of Head-and-Neck (HN) online setup precision and 

reproducibility continues to be an active field of study, especially for intensity 

modulated radiotherapy (IMRT) treatments. The purpose of this study is to 

quantify the magnitude and distribution of inter- and intra-fraction and residual 

setup errors for treatment of HN IMRT patients using three different in-room 

imaging systems. 

Materials: Eleven patients undergoing IMRT of the HN were selected. Three 

in-room imaging systems, kV-based Brainlab ExacTrac, Varian kV OBI and 

CBCT, were utilized to assess their performance in reducing inter-, intrafractional 

and residual setup errors. Each patient was initially positioned by 

aligning skin marks from their previous simulation to the lasers. Daily corrections 

were based on the shifts obtained with the OBI. Prior to the OBI-based 

correction, a daily ExacTrac images were also acquired and the shifts were 

obtained. In addition, a weekly volumetric CBCT for each patient was acquired 

and the shifts were obtained prior to applying the OBI-based shifts. 

After the OBI-based shifts were applied, a second daily ExacTrac images 

were taken and the shifts were obtained to estimate the residual setup errors. 

Finally, a third daily ExacTrac images were taken at the end of the daily 

treatment to determine the intra-fraction setup errors. The daily shifts in lateral 

(LR), longitudinal (SI) and vertical (AP) directions, along with the 3D shift 

vector, obtained with OBI images from same patients were quantitatively compared 

to the corresponding shifts obtained with ExacTrac and CBCT images. 

Results: The differences between the mean shifts in each direction and mean 

3D shift vector with three systems were


1356 poster 

COMPARISON ON- AND OFF-LINE REGISTRATION FOR PATIENT 

WITH RECTUM CANCER PERFORMED WITH MEGAVOLTAGE 

CONE BEAM CT (MVCBCT) 

P. Kukolowicz 1 , S. Zielinska-Dabrowska 1 , P. Czebek-Szebek 1 

1 HOLYCROSS CANCER CENTER, Medical Physics Department, Kielce, 

Poland 

Purpose: Daily accurate patient positioning is one of the prerequisites of 

modern radiotherapy. In the HCC the MVCBCT system was installed. After 

commissioning and phantom tests the system was implemented clinically. 

The first clinical data of the set-up control of patients with rectum cancer are 

presented. The special concern is given to the validity of on-line registration 

made by radiation technologists (RTTs). 

Materials: The set up control was performed for 23 patients treated preoperatively 

with 5 fractions (5 x 5 Gy). For each patient lying prone planning 

CT was made. The planning CT data consisted of 5 mm slices acquired at 

5 mm steps with 512 x 512 pixels per slice in the irradiated volume. The 

3 field technique, one open PA field and two wedge lateral fields was used. 

After set-up a patient in treatment position the MVCBCT was made with 8 

MU protocol (about 6 cGy at isocenter). The images were reconstructed with 

1mm step in the matrix 512 x 512 pixels. Three images were presented in 

the axial-sagital-coronal subwindows of the Adaptive Targeting task card of 

the Therapist application (Siemens Coherence Therapist Workspace Version 

2.0.125) to the RTTs. Each set of images acquired with the MVCBCT was 

registered with the appropriate set of CT planning images. The registration 

was performed by RTTs either automatically or manually. After registration 

the information about the displacement of a patient with respect to planning 

position was obtained. The same day the off-line registration was compared. 

The set-up uncertainty was evaluated for patient was calculated in terms of 

random and systematic errors. 

Results: The average time needed to perform the control was 4 minutes. 

In the lateral (lat) direction, 17% required a shift of >4mm, 8% required a 

shift of >5mm, and 6% required a shift of >6mm. In the longitudinal (long) 

direction, 21% required a shift of >4mm, 11% required a shift of >5mm, and 

9% required a shift of >6mm. In the vertical (vert) direction, 33% required 

a shift of >4mm, 17% required a shift of >5mm, and 10% required a shift of 

>6mm. The systematic errors for lat, long, vert directions were 0.27, 0.31 and 

0.42 cm for on-line and 0.27, 0.19 and 0.37 cm for off-line respectively. The 

random errors for lat, long, vert directions were 0.23, 0.17 and 0.24 cm for online 

and 0.21, 0.15 and 0.29cm for off-line respectively. In the lat, long, vert 

directions the discrepancy between on-line and off-line results of registration 

were >2mm in 18%, 12%, 20% of cases, >3mm in 7%, 7%, 13% and >4mm 

in less then 4% of cases respectively. 

Conclusions: This study demonstrated that the MVCBCT and syngo Adaptive 

Targeting software might be effectively used for on-line set-up control. 

Some discrepancies between the on- and off-line registrations were observed. 

1357 poster 

EVALUATION OF INTRAFRACTION MOTION FOR FRAMELESS 

STEREOTACTIC RADIOSURGERY (SRS) TREATMENT WITH THE 

MODIFIED BRAINLAB MASK SYSTEM 

E. Gete 1 , R. Shaffer 2 , R. Lee 1 , M. McKenzie 2 , V. Moiseenko 1 

1 BC CANCER AGENCY, Medical Physics, Vancouver, Canada 

2 BC CANCER AGENCY, Radiation Oncology, Vancouver, Canada 

Purpose: To determine the intrafraction motion of patients immobilized with 

the BrainLAB thermoplastic mask during intracranial frameless stereotactic 

radiosurgery (SRS) treatment. 

Materials: Ten patients were treated with SRS for up to three intracranial 

metastases and were immobilized with the BrainLAB frameless SRS system. 

Patient immobilization was carried out using a custom-made thermoplastic 

mask, to which we have added an additional bite block in order to restrict rotational 

motion. Patient positioning in the treatment room was achieved using 

the ExacTrac x-ray system. A pair of stereoscopic x-ray images were taken 

and co-registered with the corresponding digitally reconstructed radiographs 

computed from the planning CT scan. Based on this fusion, the translational 

and rotational couch moves needed to bring the isocentre to the desired position 

were calculated. The required corrections were applied using the Brain- 

LAB Robotic Tilt Module. Another pair of stereoscopic x-rays was then acquired 

in order to verify the patient’s position before treatment was delivered. 

For this study, a further pair of verification x-rays were acquired after the treatment 

was completed. Intrafraction motion was determined by comparing the 

displacement and rotation between the x-ray images acquired immediately 

prior to treatment and those acquired after completion of treatment. 

Results: In the first four patients, six metastases were treated. The mean 

intrafraction motion in these patients was determined to be: 0.01 ± 0.12 mm 

Antero-Posteriorly, 0.11 ± 0.22 mm laterally and -0.06 ± 0.20 mm in the 

Superior-Inferior direction. Rotational motions were 0.22 ± 0.38, 0.0 ± 0.17 

and -0.08 ± 0.16 degrees about the vertical, lateral and longitudinal axes of 

rotation respectively. 

Conclusions: Translational and rotational intrafraction motion with the modified 

BrainLAB mask system is less than 0.5 mm and 0.5 degrees. 

1358 poster 

EVALUATION OF SET-UP MODIFICATIONS IN RADIOTHERAPY OF 

HEAD & NECK AFTER A SCHEDULED TREATMENT REPLANNING 

V. Frascino 1 , M. Balducci 1 , G. R. D’Agostino 1 , G. Mantini 1 , G. C. 

Mattiucci 1 , N. Dinapoli 1 , M. A. Gambacorta 1 , E. Mazzeo 1 , P. Bonomo 1 , 

S. Patriccioli 1 , V. Valentini 1 

1 UNIVERSITÀ CATTOLICA DEL SACRO CUORE, Radiotherapy, Rome, Italy 

Purpose: The loss of body weight can have a detrimental impact on the 

immobilization of patient with thermoplastic mask, and consequently on the 

dose distribution. This findings is particularly important when the treatment is 

performed in IMRT. In this study we examined the impact on set-up accuracy 

of a programmed daily portal imaging off-line evaluation, aiming to warrant a 

set-up error < 3 mm. 

Materials: Patients with locally advanced head & neck candidate to undergo 

IMRT were enrolled into the study. A portal imaging verification of set-up was 

obtained at least twice-a-week. A treatment replanning was programmed independently 

from the volume and/or set-up modifications before reaching the 

doses of 27, 45, 54 Gy, or earlier in the case of patient’ body loss exceeding 

10%. A new termoplastic mask was built whenever on CT-scan a gap 

between mask and body surface was revealed. Statistical analysis was performed 

by MedCalc software (Mariakerk, Belgium). 

Results: From May to December 2007, 12 patients were enrolled into the 

study. A total of 117 portal imaging were acquired (median per patient 10, 

range 4-21) and 37 treatment plans were designed (median per patient 3, 

range 3-4). The median set-up errors registered were: 2,6 mm longitudinally 

(CC, range 0-1.0), 0.34 laterally (LL, range 0-1.1), 0 vertically (AP, range 0- 

0.8). The analysis of variance did not find any statistical difference among the 

three classes of set-up errors (CC: p=0.31; LL: p=0.37; AP: p=0.09). Variations 

in set-up resulted to be independent from the patient, the treatment plan 

per patient, and the reached dose. The set-up errors were also found independent 

from the patient body loss. 

Conclusions: Our data suggest that this programme could warrant a 3mmtolerance 

in off-line set-up controls of patients with head & neck cancer submitted 

to IMRT. 

1359 poster 

EVALUATION OF THE DOSE DISTRIBUTION PERTURBATION DUE 

TO SETUP ERROR IN BREAST RADIOTHERAPY 

E. Kiatsi 1 , M. Kotzasarlidou 1 , K. Theodorou 2 , E. Destouni 3 , A. Makridou 

1 

1 

THEAGENEIO ANTICANCER CENTER, Medical Physics Department, 

Thessaloniki, Greece 

2 

UNIVERSITY OF THESSALY, Medical Physics, Larissa, Greece 

3 

THEAGENEIO ANTICANCER CENTER, Radiotherapy Department, Thessa- 

loniki, Greece 

Purpose: The aim of this work is to determine the dose perturbation due to 

setup error in tangential breast irradiation and to evaluate it based on physical 

and biological parameters. 

Materials: For that purpose 20 consecutive breast cancer patients treated 

with 2 tangential fields at the Radiotherapy Dept. of Theageneio Anticancer 

Center, Thessaloniki, Greece, were evaluated with everyday electronic portal 

images. Each patient had undergone CT in treatment position, 3D target and 

organ definition and 3D treatment planning and dose calculation. The setup 

error determination was based on the 2D geometrical difference between the 

EPID images and the extracted DRR as well as on different geometrical parameters 

such as CLD, CIW, CCD and CBESD. The treatment plan was then 

recalculated for every patient based on the determined error. 

Results: DVHs, TCP and NTCP for every organ were calculated for each 

plan and statistical analysis was performed correlating the setup error with 

the treatment outcome and normal tissue complications. 

Conclusions: The setup error in isocenter should be strictly kept below 3 

mm. The study shows that portal images are a good indicator for setup 

accuracy determination in the case of tangential fields and they should be 

performed in a regular manner. 

1360 poster 

EVALUATION OF THREE DIMENSIONAL SET-UP ERRORS IN 3D- 

CONFORMAL RADIOTHERAPY TO THE PROSTATE AT ST LUKE?S 

CANCER CENTRE USING ELECTRONIC PORTAL IMAGING. 

E. Alexander 1 , K. Freeman 1 , T. Guerrero Urbano 1 

1 ST LUKE’S CANCER CENTRE, Radiotherapy, Guilford, United Kingdom 

Purpose: To quantify set-up errors in 3D- Conformal Radiotherapy (3D-CRT)

in prostate cancer at our institution prior to IMRT implementation and to determine 

if set-up during the first fraction is a good indicator for the rest of the 

treatment course. 

Materials: 50 patients treated between May and August 2007 were retrospectively 

assessed. They were treated in the supine position with ankle 

stocks. Electronic portal images (EPIs) were taken daily for the first three 

fractions and weekly thereafter. Off-line matching was performed using digitally 

reconstructed radiographs (DRRs) as reference images, with a level of 

action for isocentre movement set at 2.5mm. Group systematic (Σ) and random 

(σ) errors were calculated and set-up margins were calculated using the 

Van Herk margin formula. First fraction set up displacements and the systematic 

error of the first 3 fractions were correlated with the mean displacement 

during the rest of the treatment course using Spearman’s rho correlation coefficient 

test. 

Results: 2985 displacement measurements were taken from 995 orthogonal 

EPIs. 93% of all transitional displacements were ≤3mm and 99% ≤5mm. 

The group systematic error (Σ) was 0.6mm (±0.9SD) in the right-left (R-L), 

0.9mm (±1SD) in the anterior-posterior (A-P) and 0.3mm (±0.6SD) in the 

supero-inferior directions. A small difference in the S-I error was observed 

when analyzing the lateral (0.4±0.8) and A-P (0.3±0.7) images, likely to 

represent intra-fraction motion. The corresponding SDs of the individual random 

errors were ±0.7mm (R-L), ±0.8mm (A-P), ±0.4mm (S-I). The calculated 

contribution to CTV to PTV margins from set-up errors were 2mm 

(R-L), 3mm (A-P) and 1mm (S-I). Average displacements on the first fraction 

were 0.3±1.4mm in the S-I and 1.6±2.2mm in both the R-L and A-P directions. 

The systematic errors of the first 3 fractions were 0.2±1.1mm (S-I), 

1.2±1.5mm (R-L) and 1.6±2mm (A-P). A strong correlation was found between 

the displacements in the 1st fraction and the systematic error of the 1st 

3 fractions: A-P (r=0.9, p=0.01), S-I (r=0.8, p=0.01) and R-L (r=0.7, p=0.01). 

Average displacements during the whole treatment course correlated with 1st 

fraction S-I (r=0.5, p=0.01) and A-P (r=0.3, p=0.05), and the S-I systematic 

error of the 1st 3 fractions S-I (r=0.4, p=0.01). 

Conclusions: Our results compare favourably with published data and are 

adequate for the implementation of IMRT. Set-up during the first fraction correlates 

with the systematic error of the first 3 fractions and is a good indicator 

of set-up during the course of treatment. 

1361 poster 

FIRST EXPERIENCES WITH A NOVEL NON-INVASIVE HEAD 

FIXATION DEVICE (ESARTE) FOR STEREOTACTIC CEREBRAL 

RADIOTHERAPY 

M. Nevinny 1 , A. Posch 1 , M. Brueggl 1 , T. Seppi 1 , P. Lukas 1 

1 MEDICAL UNIVERSITY INNSBRUCK, Department of Radiooncology, 

Innsbruck, Austria 

Purpose: The reproducible and stabile fixation of the head is the crucial prerequisite 

for the performance of a fractionated or single-dose stereotactic radiation 

therapy (RT) in the head and neck region. For this purpose, a variety 

of invasive and non-invasive positioning systems are available of differing 

fixing precision. In the presented study, we evaluated a novel non-invasive 

head-fixation device based on dental and upper jaw impression regarding its 

precision and practicability. The ESARTE head fixation uses the Leksell coordinate 

system and disposes of a couch adaptor allowing a sub-millimetre 

positioning accuracy. 

Materials: Ten patients with intracerebral tumours were precisely positioned 

using the ESARTE system and treated with at least 10 RT fractions. Before 

each radiotherapy session, a cone beam CT was performed to assess the 

system accuracy. The reproducibility of repositioning was measured by image 

fusion of the cone beam and the planning CT scans related to the bony 

structures. 

Results: The maximal detected xyz-deviation never exceeded 3 mm. The 

maximum variance in axial rotation was always below 1.0 degree. Mean positioning 

drift was 0.99 ±0.6 mm (x-axis), 0.91 ±0.8 mm (y-axis), and 0.13 

±0.08 mm (z-axis), respectively. 

Conclusions: The ESARTE head-fixation system allows a precise and reproducible 

head fixation for single-shot and fractionated stereotactic irradiation of 

targets head and neck region. Therefore, a safety margin of maximally 3 mm 

should suffice if a precise verification of patient positioning by cone beam CT 

scanning is not available. 

1362 poster 

FRAMELESS HYPOFRACTIONATED STEREOTACTIC RADIO- 

THERAPY USING CONE BEAM CT IMAGE GUIDANCE FOR 

INTRA-CRANIAL METASTASES. 

S. Fabbri 1 , F. Fiorica 2 , S. Lappi 1 , S. Ursino 2 , C. Flammia 1 , E. De 

Guglielmo 1 , L. Perazzini 1 , B. Boarini 2 , F. Cartei 2 

1 S. ANNA HOSPITAL, Health Physics, Ferrara, Italy 

2 S. ANNA HOSPITAL, Radiotherapy, Ferrara, Italy 

Purpose: Hypofractionated stereotactic radiotherapy (HSRT) for lesions in 

the brain typically uses relocatable systems to obtain target localization and 


S 433 

immobilization. This study was designed to determine the set-up displacements 

during frameless HSRT using a heat-flexible mask and a set-up correction 

CBCT guided. 

Materials: Data from 12 patients undergoing 40 stereotactic radiation therapy 

procedures in 2007, were analyzed. In all patients, a heat-flexible mask 

with 3-points was employed. Prior to treatment a CBCT scan (On-Board Imager, 

Varian Medical Systems) was acquired and matched to the planning CT 

aligning bone anatomy: the dispacements obtained were corrected on-line. A 

second CBCT was used to confirm the re-positioning shifts. We analyzed 

isocenter translations in all three axes, the absolute magnitude of isocenter 

dislocation. The rotations were assessed using an independent image registration 

software (Syntegra, Philips). 

Results: The average applied shifts for the three axes were 0.8 ± 1.2 mm, 

0.3 ± 0.8 mm and 0.2 ± 0.3 mm respectively for the lateral (X), caudocranial 

(Y) and antero-posterior (Z) directions. The absolute magnitude of the 

isocenter dislocation was 1.6 ± 0.7 mm. The average rotational deviation 

around Z axis was 0.05 ± 0.64 ◦ ; no detectable rotational deviations around 

the X and Y axes were observed. 

Conclusions: A heat-flexible mask provides an immobilization accuracy of 

the patient similar to relocatable systems. Furthermore, the use of CBCT allows 

to determine and correct the set-up errors to obtain the same positioning 

of the planning CT. 

1363 poster 

IMAGE-BASED QUANTIFICATION OF TARGET VOLUME MARGIN 

FOR STEREOTACTIC RADIOSURGERY 

G. Delpon 1 , G. Brunet 1 , D. Di Peri 2 , D. Menegalli-Boggelli 3 , F. Thillays 2 , 

A. Lisbona 1 

1 

CLCC NANTES CENTRE RENE GAUDUCHEAU, Medical Physics, Nantes 

Saint-Herblain, France 

2 

CLCC NANTES CENTRE RENE GAUDUCHEAU, Radiotherapy, Nantes 

Saint-Herblain, France 

3 

NANTES HOSPITAL, Neurosurgery, Nantes Saint-Herblain, France 

Purpose: For stereotactic radiosurgery treatments, the target volume is 

drawn either by the radiotherapist or the neurosurgeon. The goal of this study 

was to define the margins that have to be applied to this volume using the ExacTrac 

(BrainLAB) image guided radiotherapy system. 

Materials: 33 patients (44 localisations) were treated by stereotactic radiosurgery 

with a Novalis linac (BrainLAB). For each patient, an invasive stereotactic 

frame and a positioning box were used. Normally dedicated to fractionated 

treatments, the ExacTrac system, (consisting of two recessed kV x-ray 

units and two ceiling-mounted flat panel detectors) was used to validate the 

patient positioning before treatment delivery for each isocenter. Translation 

shifts in three axes were derived from an automatic registration between kV 

images and reference images calculated from the planning CT scan. In this 

study, as recommended by BrainLAB, shifts were not applied. 

Results: In this study, the mean of absolute values of translation shifts 

was less or equal to 0.6mm in all axes (0.6+/-0.4mm left-right, 0.5+/-0.4mm 

superior-inferior and 0.6+/-0.5mm anterior-posterior). Measured shifts in the 

left-right direction were overestimated due to our geometric calibration of the 

isocenter position using the Winston-Lutz test. This calibration lead to a 

0.5mm systematic lateral shift between the light simulation (corresponding 

to the ExacTrac isocenter) and the sagittal laser (corresponding to the Novalis 

isocenter determined with the Winston-Lutz test). If this systematic error 

was subtracted, the mean shift was 0.3+/-0.3mm, and in only one case larger 

than 1mm. In the anterior-posterior and superior-inferior directions, our results 

reflect the accuracy of the system with the use of a frame. About 85% 

of shifts were less than 1mm. 

Conclusions: Our results indicate that the Exactrac system should not be 

used due to the systematic error and the small size of fields for stereostatic 

radiosurgery treatments. Moreover this study lead us to apply a 0.5mm margin 

to the target volume in all directions (left, right, anterior, posterior, superior, 

inferior) when planning radiosurgery treatments, in order to take into account 

the uncertainties of the global treatment. To confirm this 0.5mm value, 

a complementary study will evaluate the dose distributions that would have 

been obtained if the margin was applied to the target volume and if the shifts 

derived from the treatment session were applied to the isocenter position. 

1364 poster 

IMPROVEMENT OF PORTAL IMAGE BY MEANS OF GAUSSIAN 

HISTOGRAM MATCHING AND EDGE ENHANCEMENT 

R. Dávila-Fajardo 1 , A. Cámara-Turbí 1 , F. López-Soler 1 , A. González-López 

2 , J. D. Palma-Copete 2 


Oncología Radioterápica, Murcia, Spain 


Radiofísica y Protección Radiológica, Murcia, Spain 

Purpose: Portal image is a basic tool for quality assurance in radiotherapy. 

Sometimes the software supplied by manufacturers just provides the user


with the option for modifying the window and level, occasionally for histogram 

equalization. Histogram matching, on the other hand, is a generalization of 

histogram equalization. It is a method to enhance the image contrast by 

matching an original histogram of grey values to another histogram distribution, 

e.g. Gaussian. A Gaussian transformation of histogram is aimed to 

assign more grey level values to intermediate original levels (which contain 

the most relevant information of the image). Among the most useful improvements 

that can be achieved in image enhancement is the edge enhancement. 

Edge enhancement is easily carried out by a number of algorithms that can 

be implemented without too much effort. The purpose of this study is to show 

the improvement of portal image by Gaussian histogram matching and edge 

enhancement. 

Materials: A computer application was developed to import the portal images 

from our commercial portal image system. After removing all the margins 

not containing any anatomical information a median filter is carried out to 

eliminate specks. Then a Gaussian histogram matching followed by a Sobel 

edge enhancement filter is applied. Three observers studied the anatomical 

areas of head and neck, pelvis and thorax (total of 18 images). 

Results: Examples of the original image and the processed images are 

shown in the figure. In every anatomical area the three observers evaluated 

the in-house processed image better than the system processed images. 

Conclusions: The image quality improvement obtained following the simple 

algorithms presented suggests that more powerful image enhancement tools 

should be provided to the user in order to validate patient positioning from 

portal images. 

1365 poster 

IMPROVEMENT OF TREATMENT PRECISION DURING EXTRACRA- 

NIAL RADIOSURGERY 

G. Wozniak 1 , A. Grzadziel 2 , A. Idasiak 1 , S. Bacia 2 , L. Miszczyk 1 

1 

CENTRE OF ONCOLOGY, MSC MEMORIAL INSTITUTE GLIWICE, Radiotherapy 

Department, Gliwice, Poland 

2 

CENTRE OF ONCOLOGY, MSC MEMORIAL INSTITUTE GLIWICE, Department 

of Radiotherapy and Brachytherapy Planning, Gliwice, Poland 

Purpose: An evaluation of the patient‘s positioning precision during extracranial 

radiosurgery using Exac Trac system. 

Materials: Set up errors measurements of 26 patients treated with extracranial 

radiosurgery were done. All patients were immobilized using vacuum 

mould. After establishing of isocenter using optical infra red markers attached 

to skin, portal images of two orthogonals set up fields were compared 

to DRRs (generated in Brain Lab treatment planning system). Shift 

measurements in transversal (X), longitudinal (Z) and vertical (Y) axes were 

performed. All cases were divided into three groups according to the tumor 

location (thorax, abdomen and pelvis). Then mean of shifts and standard 

deviation were estimated 

Results: Means of shift were in X axis 4.5mm (SD ±3.8), in Y axis 3.3 mm 

(SD ±2.2) and 6.2 mm (SD ±4.8). In Y axis. The largest means of shift in X 

and Y axes were observed in the abdominal region, and in Z axis in the pelvic 

region. According to van Herk‘s formula, we estimated the PTV‘s margins 

for the used immobilization and an isocenter set up methods. It should be 

around 9.5mm in X, 5.5mm in Y and as many as 12 mm in Z axis; which are 

too large and unacceptable for radiosurgery treatment. 

Conclusions: The obtain results allow to form conclusion that precision of 

the isocenter setting up based only on infrared detectors is unsatisfacory and 

requires a portal verifications or other IGRT systems. 

1366 poster 

INTER- AND INTRAFRACTIONAL MOVEMENT OF THE TUMOUR IN 

EXTRACRANIAL STEREOTACTIC RADIOTHERAPY OF NSCLC 

H. Jensen 1 , M. Hjelm-Hansen 1 , O. Hansen 2 , C. Brink 1 

1 

LABORATORY OF RADIATION PHYSICS, Odense University Hospital, 

DK-5000 Odense, Denmark 

2 

DEPT. OF ONCOLOGY, Odense University Hospital, DK-5000 Odense C, 

Denmark 

Purpose: The purpose of this study is to determinate the appropriate treatment 

planning margins related to inter- and intra-fractional respiration induced 

movements as well as setup accuracy in a stereotactic body frame for stereotactic 

treatments of NSCLC patients. 

Materials: From August 2005 to January 2008, 17 patients with NSCLC 

where given a stereotactic treatment. The patients were scanned with normal 

and uncoached respiration without use of abdominal compression. Each 

patient had CT-scans performed at four occasions throughout the treatment: 

As part of the CT-simulation and before the 3 radiotherapy treatment. At 

every occasion six individual CT-scans covering the tumour volume were obtained. 

In this way 24 scans where obtained from each patient. In each 

CT-scan the maximum positions of the tumour where located in all 6 directions, 

represented by the top, bottom, anterior, posterior, left and right part of 

the tumour. These coordinate constitute the data of this study. A common 

reference system between the individual CT sessions is obtained by fusion of 

the patient anatomy of a given CT session with the patient anatomy of the first 

CT session. Likewise a fusion of the body frame was performed to be able 

to measured patient positioning accuracy within the frame. All fusions were 

performed in the Syntegra module in the Pinnacle3 dose planning system. 

Results: The standard deviations of the respiration induced intra-fractional 

movements were: LR: 0.8 mm, AP: 1.2 mm and CC: 2.2 mm (1 SD). The 

inter-fractional movements were: LR: 1.0 mm, AP: 1.3 mm and CC: 1.9 mm 

(1 SD). Finally the set up accuracies in the body frame were LR: 1.5 mm, 

AP: 1.1 mm and CC: 1.8 mm (1 SD). The standard deviation of all three 

uncertainties would be LR: 2.0 mm, AP: 2.1 mm and CC: 3.4 mm (1 SD) 

Conclusions: With a patient fixated in a stereotactic body frame, we conclude 

that large movements of the tumour are rarely seen within the lung. 

With consecutive scans, using a conventional CT-scanner, it is possible to 

find those patients in whom the tumour movement is large. The three discussed 

uncertainties would by use of the van Herk (IJROBP pp. 11211135, 

2000) margin recipe be 10.2 mm in the CC direction. Three possible way 

of reducing this margin could be 1) use of mid-ventilation phase (4D CT) for 

treatment planning 2) use of Cone Beam treatment position verification (registration 

of tumour not bone) 3) use of gating. Simple estimates of the effect of 

these changes is that 4D CT could reduce the margin to 8.6 mm. Cone Beam 

in combination with 4D CT would reduce the margin to 5.2 mm. However addition 

of gating would at most reduce the margin with one millimetre. Thus 

in our opinion gating is only useful for a very limited number of patient with 

substantial tumour movements. However, introduction of 4D CT and Cone 

beam verification is strongly encouraged 

1367 poster 

INTRA-ACQUISITION VARIATION: A NEW FACTOR TO TAKE INTO 

ACCOUNT FOR REDUCING SETUP UNCERTAINTIES 

S. Hol 1 , W. de Kruijf 1 , B. Smits 1 , M. van de Pol 1 

1 DR. BERNARD VERBEETEN INSTITUUT, Radiotherapy, Tilburg, Netherlands 

Purpose: To develop a work-flow to evaluate the intra-acquisition variability 

using 4D-CT-scans in lung cancer patients. 

Materials: At the CT simulator (Lightspeed RT scanner GE Medical Systems), 

patients were immobilized in a supine treatment position using an 

arm base rest device (CIVCO) and knee and foot brace devices. This CTscanner 

is equipped with respiratory monitoring device (RPM-system, Varian). 

Patients were aligned by in-room movable lasers and three skin marks 

were placed before starting the scanning procedure. First two scout-views 

were performed (coronal and sagittal). Then the 4D-CT acquisition was performed. 

Immediately after the 4D-CT acquisition, new scout-views (coronal 

and sagittal) were acquired. Afterwards, the position of the skin marks was 

verified using the laser-system. A displacement of less than 2mm (in lateral, 

superior-inferior, and anterior-posterior directions) was considered to be an 

acceptable 4D-CT-acquisition. If the displacements were larger, the whole 

CT-acquisition-procedure was repeated. Knowing the uncertain relation between 

skin marks and internal anatomy, we analyzed 53 scans for 25 patients 

who underwent a 4D-CT for lung radiotherapy. All scans met the 2 mm criterion. 

The scout-views were loaded into Theraview NT (Cablon Medical BV). 

The pre- and post 4D-CT acquisition scouts were analyzed, using this software. 

Matching was performed based on rigid visible structures such as the 

lung top and the vertebral bodies. The displacements in three directions were 

calculated. 

Results: The average displacement is 0.2mm medio-lateral, 0.1mm craniocaudal, 

and 0.5mm ventro-dorsal. The systematic error, estimated as the 

standard deviation of the measured displacements, is 1.0mm medio-lateral, 

1.0mm cranio-caudal, and 1.5mm ventro-dorsal. This systematic error con-

tributes to the total systematic error in positioning the patient at the LINAC. It 

is not known when these, generally small, displacements occur exactly (during 

the CT-acquisition itself, just after or just before the CT- acquisition). 

Conclusions: We described a practical method with minimal workload to 

analyze the intra-acquisition variability, a possibly underestimated factor in 

setup-uncertainties for long-lasting acquisition procedures like 4D-CT or for 

patients which are difficult to position. Although, in our series, the intraacquisition 

variability was generally small, we advocate the use of this method 

to be sure that the intra-acquisition variability in a certain case is small. In 

case of a large intra-acquisition variability, one might choose to repeat the 

CT-acquisition or to increase the CTV-PTV margin. 

1368 poster 

INTRA-FRACTION SET-UP VARIABILITY BASED ON MV-IMAGING 

FOR STEREOTACTIC LUNG RADIOTHERAPY 

W. de Kruijf 1 , S. van Komen 2 , M. van Wieren 1 , M. van de Pol 2 

1 

BERNARD VERBEETEN INSTITUUT, Klinische Fysica en Instrumentatie, 


2 

BERNARD VERBEETEN INSTITUUT, Radiotherapie, Tilburg, Netherlands 

Purpose: To evaluate and optimize the procedure to limit intra-fraction set-up 

variability based on MV-imaging and to assess the magnitude of this intrafraction 

set-up variability. 

Materials: Stereotactic lung radiotherapy is performed using LINACs 

equipped with camera-based EPIDs. Theraview NT (Cablon Medical B.V.) 

is used to capture and to analyse the MV-images. At the day of treatment 

MV-images (10 MU) are taken to position the patient with an on-line protocol, 

based on matching the lung top, the vertebral bodies, and the trachea with 

a DRR of the planning CT. After repositioning the patient, new MV-images (3 

MU) are made to check the table translation, but these images are also used 

as reference images for the intra-fraction set-up variability of that specific day. 

Reference contours are drawn on these MV reference images at the time the 

first beams with table rotation 0 are delivered to the patient. The plan consists 

of typically 12 beams with 4 table rotations. After each table rotation new MVimages 

(3 MU) are taken to check the position of the patient. An intra-fraction 

variation of up to 3 mm is tolerated in any of the directions. If the variation 

is larger, the patient is repositioned. Retrospective matching based on the 

anatomy for the first 10 patients has been performed by a single person (WK) 

to estimate the intra-fraction variability. 

Results: Retrospective matching of the first 10 patients led to an average 

displacement in the medio-lateral direction of 0.1 mm, in the cranio-caudal direction 

of 0.3 mm, and in the ventro-dorsal direction of 0 mm. The systematic 

error in these directions was 0.7 mm medio-lateral, 0.4 mm cranio-caudal, 

and 0.4 mm ventro-dorsal. The random error was 1.2 mm medio-lateral, 1.0 

mm cranio-caudal, and 1.2 mm ventro-dorsal. The interpretation of these errors 

is not straightforward because of the intra-fraction nature of these errors. 

Conclusions: A procedure to control the intra-fraction set-up variability has 

been established based on MV-imaging. With an action level of 3 mm, the 

patient has to be repositioned only incidentally, but the high dose per fraction 

and the low number of fractions warrants this procedure for these incidental 

cases. The intra-fraction variability is small, and the determination of 

the errors is hampered by the inter-observer and intra-observer match variability. 

However, these are also quite small, because it is easy to match MVimages 

with MV-images. The standard deviation in the medio-lateral direction 

is somewhat larger, probably due to the mobility of the trachea which has to 

be used for the lateral match when the lung top cannot be imaged. 

1369 poster 

IS IT NECESSARY A RESPIRATION-CORRELATED CT SCAN FOR 

TANGENTIAL FIELD BREAST IRRADIATION? 

A. Delana 1 , V. Vanoni 2 , L. Menegotti 1 , L. Tomio 2 , F. Ziglio 1 , S. Mussari 2 

1 SANTA CHIARA HOSPITAL, Medical Physics, Trento, Italy 

2 SANTA CHIARA HOSPITAL, Radiotherapy, Trento, Italy 

Purpose: To evaluate variability in clinical target volume (CTV) coverage and 

ipsilateral mean lung dose (MLD) using a respiration-correlated CT scan for 

early breast cancer patients treated with tangential field irradiation. 

Materials: Five patients with left breast cancer planned for radiotherapy after 

conservative surgery were included in this study. The patients were scanned 

in the treatment position using a high-speed 16-slice CT-scanner and immobilized 

in the treatment position with a customized system consisted of a breastboard 

carbon fibre (Posiboard-2 R○, CIVCO) and thermoplastic-breast support 

(Posicast R○-Thermoplastic, CIVCO). Respiration-correlated scans were 

acquired synchronously with the respiratory signal, using a deformable rubber 

belt placed across the patients waist and interfaced with the scanner and a 

retrospective image reconstruction was performed at 0%, 25%, 50% and 75% 

of end-exhale level. A total of 4 scans and approximately 60 images per patient 

were obtained Treatment was planned on an arbitrary CT image dataset 

using two breast tangential wedged half-fields. Beam geometry (gantry, collimator, 

wedge, monitor units) was superimposed to every 4D image dataset, in 

order to estimate differences in the CTV and ipsilateral lung in-field volumes 


S 435 

at different breathing phases. Isocentre was identified by the radio-opaque 

markers placed on the immobilization system during CT-simulation. CTV and 

ipsilateral lung volumes were contoured on each CT dataset by one physician, 

while the lung was automatically outlined (threshold value). DVHs were 

recalculated and the analysis was performed considering the V95% for the 

CTV and the mean lung dose (MLD). 

Results: Results obtained from the volume analysis on the 4D CT datasets 

showed variations


1371 poster 

POSITION VERIFICATION OF BREAST CANCER PATIENTS 

TREATED WITH A CONFORMAL SIMULTANEOUSLY INTEGRATED 

BOOST (SIB) TECHNIQUE 

M. Sijtsema 1 , F. van Dijk-Peters 1 , R. van der Wee 1 , J. Maduro 1 , H. P. van 

der Laan 1 , W. Dolsma 1 , H. Langendijk 1 , A. van ’t Veld 1 



Purpose: Recently, 3D-CRT with a simultaneously integrated boost (3D- 

CRT-SIB) was introduced in our institute for breast-conserving therapy. The 

3D-CRT-SIB technique has several advantages compared to the traditionally 

used sequential boost, including smaller irradiated volumes, easy clinical implementation 

and reduction of the number of fractions. Traditionally, only tangential 

beams are used for position verification of breast cancer patients. As 

a result, setup errors in the direction of the tangential beams can not be detected. 

When a SIB technique is used, such errors may result in an underdosage 

of the boost volume. Therefore, we assessed the applicability and 

necessity of a patient correction protocol using MV-images of the tangential 

beams and an additional anterior posterior (AP) beam. Furthermore, the incidence 

of the aforementioned underdosage was evaluated as well. 

Materials: For an initial group of 10 patients, two repeated 4D CT scans were 

obtained during the course of treatment in addition to the initial planning CT to 

investigate the movement by respiration. For a second group of 90 patients, 

a standard spiral CT-scan was used for treatment planning, and repeated 

CT-scans were only made if the deviations in the MV-images exceeded the 

action level. MV-images of 100 patients were collected at the LINAC of the 

tangential irradiation fields and additional anterior posterior (AP) and lateral 

verification beams. The deviation of the breast outline and the thoracic wall 

were determined. A Shrinking Action Level (SAL) correction protocol with a 

start action level of 10 mm and N=4 was used. 

Results: The repeated 4D CT scans showed that the influence of respiration 

on the position of the lumpectomy cavity can be neglected in comparison with 

that of setup errors. In 19 patients (21%) the setup errors determined from the 

MV-images exceeded the action level. In 10 of these patients, deviations were 

only observed in the AP image. In most cases, evaluation of the repeated CT 

scan showed a similar patient setup error as the MV-images. In 15 cases, 

both the boost target volume and the whole breast were still covered adequately 

with the original treatment plan because the volume of the lumpectomy 

cavity had reduced significantly. In three cases, the treatment plan had 

to be adapted because of underdosages or overdosages (85%-111%). 

Conclusions: Position verification of breast cancer treatment with a 3D-CRT- 

SIB technique requires an additional AP verification beam to detect important 

setup errors and to prevent underdosage and overdosage that appeared in 

some of these cases. 

1372 poster 

PRE-SIMULATION IN THE TREATMENT PLANNING 

P. Kaminski 1 , M. Mazur 2 , P. Czuchraniuk 2 

1 MARIA SKLODOWSKA-CURIE MEMORIAL CANCER CENTER, Medical 


2 MARIA SKLODOWSKA-CURIE MEMORIAL CANCER CENTER, Radiotherapy, 


Purpose: Poor reproducibility was noted between DRRs obtained from CTsimulation 

planning and portal images taken at the first treatment session. 

The aim of this study was to investigate usefulness of pre-simulation in improving 

this reproducibility. The term "pre-simulation" is used to describe 

activities taking place before CT-simulation. Benefits of using pre-simulation 

include CT-simulation time saving and easier patients’ symmetrical positioning 

with fluoroscopy. 

Materials: The study was carried out on patients with gynecological (N=15) 

and rectal (N=19) cancer treated on belly-board. During pre-simulation location 

of isocenter was marked on patients’ skin (two lateral points) using 

positioning lasers. Then, patients were left in that position for couple of minutes 

to allow for muscle relaxation. Next, it was checked whether current 

laser position match the previously marked points, and if not new points were 

marked (Fig. 1). During CT-simulation the latter marks were used for patients’ 

positioning. It was assumed that the latter marks reflect best location of skin 

tattoos during treatment. 

Results: After muscle relaxation the position of lateral skin marks in the 

anterior-posterior direction did not change (within limit of 2 mm) in 57% of 

patients; in 25% the shifts between both marks were within a range of 2-5 

mm and in 18% were larger than 5 mm. In the cranio-caudal direction the 

corresponding values were 78%, 22% and 4%. The position of patients on 

CT-simulator using skin marks determined during pre-simulation after muscle 

relaxation were easily reproducible in 79% of patients. The remaining 21% 

patients required new location of skin marks. The preliminary results demonstrated 

that pre-simulation improved set-up reproducibility at first irradiation 

session compared to historical control detailed data will be presented at the 

meeting. 

Conclusions: Pre-simulation reduces the risk of systematic error caused by 

muscle relaxation. 

1373 poster 

PROSPECTIVE EVALUATION OF NEW HEAD AND NECK THER- 

MOPLASTIC IMMOBILISATION SYSTEM AT ST LUKE’S CANCER 

CENTRE USING ELECTRONIC PORTAL IMAGING. 

C. Crowley 1 , C. Bunton 1 , R. Eggleton 1 , K. Mainwaring 1 , S. Sandle 1 , 

K. Freeman 1 , S. Gerard-martin 1 , T. Jordan 1 , S. Whitaker 1 , T. Guerrero 

Urbano 1 

1 ST LUKE, Guilford, United Kingdom 

Purpose: To prospectively quantify set-up errors observed during the introduction 

of a new immobilization system for head and neck and brain tumours 

at our institution prior to IMRT implementation and to determine the CTV to 

PTV margins. 

Materials: Prior to the implementation of IMRT and following a retrospective 

review of the Cabulite head and neck immobilisation system in use, it 

was decided to introduce a new thermoplastic system to optimize the patient 

pathway. The first 20 head and neck and brain tumour patients in whom 

the device was used were prospectively evaluated. Electronic portal images 

(EPIs) were taken daily for the first three fractions and weekly thereafter according 

to an in-house protocol and off-line matching performed. Simulator 

orthogonal images were used as reference images. Displacements in the 

supero-inferior (S-I), right-left (R-L) and antero-posterior (A-P) directions were 

measured in millimetres and the level of action for isocentre movement was 

set at 3mm. The group systematic and random errors were calculated and 

set-up margins obtained using the Van Herk margin formula. Weekly weight 

was recorded and correlated with the systematic and random errors using 

Spearman’s rho correlation coefficient. Skin toxicity (NCI CTC v.3.0 scale) 

was recorded weekly. 

Results: 16 patients had both the head and shoulders and 4 the head immobilized. 

The system was reported to be easy to use by mould room staff with

the time from Orfit to planning scan reduced from 5 to 1 working day. 165 

EPIs were taken and 656 displacements measured. 96% of all transitional 

displacements were ≤3mm. The group systematic error (Σ) was 0.14mm 

(±0.8SD) in the R-L, 0.2mm (±0.7SD) in the A-P and 0.1mm (±0.9SD) in the 

S-I direction. A small degree of intra-fraction motion was observed, expressed 

as a small difference in the S-I error between the lateral (0.01±1SD) and A-P 

(0.2±1SD) images. The SDs of the individual random errors were ±0.8mm 

(R-L), ±0.5mm (A-P), ±0.6mm (S-I). Median weight loss expressed as a percentage 

of baseline body weight was 5% (range 0-12%) and no statistically 

significant correlation with systematic and random errors was found. Overall, 

maximum skin toxicity was NCI CTV v.3.0 grade 3, observed in 5 (25%) patients 

with recovery observed in all. The CTV to PTV margins were calculated 

and approximated to 1mm in all directions. 

Conclusions: Initial results show this system is adequate for the implementation 

of IMRT and compare favourably to published data. Data will continue to 

be collected to a total of 50 patients to increase the robustness of our current 

results. 

1374 poster 

SETUP ERRORS IN PATIENTS WITH HEAD-AND-NECK OR LUNG 

CANCER TREATED WITH IMAGE GUIDED RADIOTHERAPY ARE 

NOT CORRELATED WITH WEIGHT, HEIGHT, BMI, OR WEIGHT 

LOSS 

J. Johansen 1 , A. Bertelsen 2 , C. R. Hansen 2 , J. Westberg 2 , O. Hansen 1 , 

C. Brink 2 

1 

ODENSE UNIVERSITY HOSPITAL, Department of Oncology, Odense, 

Denmark 

2 

ODENSE UNIVERSITY HOSPITAL, Laboratory of Radiation Physics, Odense, 

Denmark 

Purpose: The purpose of this study was to quantify the setup errors of patient 

positioning during IGRT and to correlate setup errors to patient-specific 

factors such as weight, height, BMI, and weight loss. 

Materials: 34 consecutively treated head-and-neck cancer patients (H&N) 

and 20 lung cancer patients were investigated. Patients were positioned using 

customized immobilization devices consisting of a vacuum cushion with a 

full thermoplastic face mask for H&N while lung cancer patients were immobilized 

with arms up in a thermoplastic shell from the chin to the umbilicus. 

Treatment was given in supine position on an Elekta Synergy accelerator. 

Cone beam acquisitions were obtained according to a standardized Action 

Limit protocol and compared to pre-treatment CT images. Patient position at 

treatment was assessed using an automatic grey scale matching algorithm 

in a predefined volume (clip box) according to set-up protocols for H&N and 

lung. The average 3D deviation from three initial cone beam scans was compared 

to deviations at the 10th and 20th treatment session and correlated by 

linear regression analysis to height, weight, and BMI, and in H&N to weight 

loss as expressed by the relative weight change over time. 

Results: The SD of the translational and rotational setup errors during the 

first three sessions were 0.9 mm (Left-Right), 1.1 mm (Anterior-Posterior), 

0.7 mm (Cranio-Caudal) and 0.7 (LR-axis), 0.5 (AP-axis), and 0.7 (CC-axis) 

for H&N. The equivalent data for lung cancer patients were 1.1 mm (LR), 1.1 

mm (AP), 1.5 mm (CC) and 0.5 (LR-axis), 0.6 (AP-axis), and 0.4 (CC-axis). 

The median BMI for H&N and lung at the beginning of treatment was 25.8 

(17.6-39.7) and 23.7 (17.4-38.8), respectively. Overweight (BMI>25) was observed 

in 46% (25/54). The median weekly weight change for H&N was -0.3% 

(-2.0% to 1.1%). With H&N and lung cancer analyzed separately, no statistically 

significant correlation was observed between setup errors and height, 

weight, BMI, or weight change during treatment, irrespectively whether the 

3D deviations from the initial three cone beam scans or scans from the 10th 

or 20th treatment session were used. 

Conclusions: No correlation was observed between the magnitude of setup 

errors during IGRT and patient-related factors such as height, weight, BMI, 

and weight loss. The present immobilization has ensured a safe positioning 

during radiotherapy despite weight loss and a large proportion of overweight 

patients. 

1375 poster 

TREATMENT SETUP UNCERTAINTIES QUANTIFIED BY MEGAVOLT- 

AGE CT IMAGING 

S. Stathakis 1 , C. Shi 1 , P. Mavroidis 2 , G. Swanson 1 , C. Ramer 1 , V. Sarkar 

1 , B. Costa Ferreira 3 , G. Komisopoulos 4 , D. Giantsoudi 1 , N. Papanikolaou 

1 






4 UNIVERSITY HOSPITAL OF LARISSA, Department of Medical Physics, 

Larissa, Greece 

Purpose: To estimate the impact in effectiveness due to the dosimetric dis- 


S 437 

crepancies between planned and delivered dose distributions in prostate cancer 

radiotherapy. The delivered dose distributions were calculated taking into 

account the patient shifts in three directions, which were registered by using 

the on-board megavoltage computed tomography (MVCT) capabilities of the 

tomotherapy HiArt unit. 

Materials: For the calculations co-registrations between daily MVCT and 

planning CT were used. An MVCT image was acquired before the delivery 

of each fraction and it was registered with the planning kilovoltage computed 

tomography (kVCT) images. The registration criteria were based on fiducial 

markers and contoured regions of interest. The registration results for the 

lateral, superior-inferior and anterior-posterior shifts were recorded in an inhouse 

developed database for further evaluation and analysis. For a typical 

prostate cancer patient the dose distribution of the Helical Tomotherapy plan 

and that of the average shifted delivery registration were compared using the 

biologically effective uniform dose (BEUD) together with the complication-free 

tumor control probability (P+). 

Results: The co-registration process showed that the shifts observed in the 

vertical, longitudinal and lateral directions were 10.7, 4.0 and 0.5 mm, respectively. 

For the planned and delivered dose distributions, at the optimum dose 

levels the P+ values are 84.7% and 84.0% for a BEUDITV of 75.9 Gy, respectively. 

The respective total control probabilities, PB are 93.0% and 92.9%, 

whereas the corresponding total complication probabilities, PI are 8.3% and 

8.9%. The tissue response probabilities are 95.6% and 95.5% for the GTV, 

97.4% and 97.3% for the seminal vesicles, 0.8% and 0.7% for bladder and 

7.6% and 8.3% for rectum. At the initial dose prescription the expected response 

probabilities would change to 81.7% and 60.0% for the P+, 86.4% 

and 61.6% for the PB and 4.7% and 1.6% for the PI, respectively. 

Conclusions: By using the information that MVCT co-registration provides, a 

better estimation of the delivered treatment can be made. This powerful tool 

can potentially reduce the margins used for planning with the tomotherapy 

treatment planning system, delivering high doses to the target while sparing 

even more critical structures. To be able to evaluate clinical cases, which are 

similar, traditional dose based evaluation tools should be complemented by 

radiobiological measures.

S 438 PHYSICS AND TECHNOLOGY : PROTONS AND IONS 

Physics and technology : Protons 

and ions 

1376 poster 

"OPTIS2" - THE NEW GENERATION OF OCULAR PROTON THER- 

APY 

J. Heufelder 1 , J. Verwey 1 , M. J. van Goethem 2 , L. Zografos 3 , M. Jermann 

2 , G. Goitein 1 , E. Hug 1 

1 

PAUL SCHERRER INSTITUT, Centre for Proton Radiation Therapy, 

Villigen-PSI, Switzerland 

2 

PAUL SCHERRER INSTITUT, Villigen-PSI, Switzerland 

3 

HÔPITAL OPHTALMIQUE JULES GONIN, Oncologie Oculaire, Lausanne, 

Switzerland 

Purpose: Since 1984 nearly 5000 patients with eye tumors, primarily ocular 

melanomas, have been treated at the Paul Scherrer Institute using a 72 MeV 

Phillips Cyclotron as part of the OPTIS program. In February 2007 we started 

clinical operation of the new 250 MeV superconducting cyclotron (COMET), 

dedicated exclusively for patient treatments. Purpose of "OPTIS2" is the creation 

of a new facility for the treatment of ocular tumors based on COMET, 

to seamlessly transfer patient care from OPTIS to OPTIS2, and to match the 

clinical success of OPTIS by reproducing its beam parameters. 

Materials: The major challenge with a cyclotron producing high energy protons 

of >200 MeV is the maximum beam current available for the eye treatments: 

The penetration depth of the protons is too big, thus requiring to decelerate 

them to a suitable energy of around 70 MeV. This process is highly 

inefficient; resulting in loss of up to 99.5% of initial protons and consequently 

leading to a very low dose rate. Few solutions present themselves in order 

to produce dose rates >15 Gy/min. First: Increasing the efficiency of the 

degrading process mostly performed at eye beam lines of other high energy 

proton facilities. The price is an increased distal fall off after the Bragg peak 

(over 2.0 mm instead of 1.2 mm). Second: using multiring double scattering 

systems, which have an increased efficiency compared to the typically used 

single scattering systems (e.g. OPTIS). The major challenge for the OPTIS2 

team with this different scattering system was to reproduce the beam parameters 

of OPTIS as close as possible. 

Results: Monte-Carlo simulations and the results of the first commissioning 

measurements demonstrate, that the OPTIS beam parameters can be closely 

reproduced: Distal fall off and lateral penumbra, both measured from 90% to 

10% dose, are comparable (distal: 1.2 mm and lateral with and without last 

part of the nozzle: 3.6 mm / 2.0 mm for OPTIS2 compared to distal: 1.1 mm 

and lateral: 2.3 mm for OPTIS). The dose rate is approx 15 Gy/min (OPTIS2) 

versus 30 to 60 Gy/min (OPTIS). Without the last part of the nozzle of OPTIS2 

flatness and symmetry were superior to OPTIS. 

Conclusions: OPTIS2 is designed and built from scratch, providing a continuation 

of the existing proton therapy program OPTIS with comparable beam 

characteristics, while obtaining its protons from COMET. Beam commissioning 

and system testing are currently ongoing. First results are promising but 

modification of the nozzle is necessary. First patient treatment is scheduled 

for summer 2008. 

1377 poster 

A COMPLETE PREDICTIVE MODEL FOR SOBP FIELD DELIVERY 

M. Engelsman 1 , H. M. Lu 1 , D. Herrup 1 , H. Kooy 1 

1 MASSACHUSETTS GENERAL HOSPITAL AND HARVARD MEDICAL SCHOOL, 


Purpose: The number of and experience with proton therapy machines is 

rapidly increasing, but many clinical physics aspects are not nearly the routine 

practice of photon therapy. We report on our establishment of a complete 

field calibration predictive model for the passive scattering mode of the IBA 

universal nozzle. 

Materials: Since the start of clinical operations in November 2001 we have 

delivered 13,000 unique clinical treatment fields. The per-field calibration 

process consists of ascertaining the range (R) and modulation (M) of the 

clinically delivered spread-out Bragg peak (SOBP), as well as the output factor 

(F ) in cGy/MU. Current patient load requires about 20 new calibrations 

per day. Increasing familiarity with and confidence in our treatment control 

system (TCS) has allowed us to change the calibration process from individual 

per-field measurements to a system-wide approach. Essential in the 

re-commissioning of our TCS has been to step away from the historical definition 

of modulation width and redefine it to be the distance between the 

proximal 98 % to distal 90 % isodose level, M98. 

Results: Our IBA universal nozzle in double scattering mode spans 8 different 

"options," characterized by a combination of range modulator track and 

second scatterer, and by 3 sub-options with individual beam-modulation functions. 

A single time-resolved depth-dose scan per sub-option creates the 

beam-modulation profile to create flat SOBP’s, and allows accurate delivery 

of any M98. An additional set of 12 output measurements per option establishes 

the output model for all R/M98 combinations. Establishing the model to 

accurately predict R, M and F takes four hours (only 2 hours with pre-existing 

beam-modulation functions). Model validation, prior to clinical release, takes 

another two hours per option. We now predict 99% of our fields, choosing to 

measure only radiosurgery treatment fields having an M98 of less then 2 cm. 

Conclusions: Our complete control of SOBP field delivery is valid for all new 

fields and predicts the range within 1 mm, the modulation within 3 mm or 3 % 

and the output within 1.6 % (1SD). We currently perform weekly system-wide 

measurements, spot-calibrations of a handful of SOBPs taking 2 hours in 

total, to validate the continuing accuracy of these predictions. The complete 

predictive model has freed up a significant amount of beam-time, room-time 

and physicist-time for other developments. 

1378 poster 

COMPARISON OF CONFORMAL PROTON AND PHOTON THERAPY 


M. Mumot 1 , J. Malicki 2 , Y. Luchin 1 

1 JOINT INSTITUTE FOR NUCLEAR RESEARCH, Laboratory of Nuclear 

Problems, Dubna, Russian Federation 

2 GREAT POLAND CANCER CENTRE, Department of Medical Physics, 

Poznan, Poland 

Purpose: To analyze the benefits in chosen clinical cases for dose distributions 

obtained for conformal proton therapy over the conformal photon therapy, 

using conformity indices. 

Materials: We have chosen several patients with different tumours in head 

region. Two different radiation treatment plans have been prepared with our 

treatment planning system for each patient one using conventional photon 

beam technique and second using passive conformal proton therapy. For 

each plan we tried to achieve the best possible conformity based on our physician 

experience. Patients were selected in the most typical cases treated in 

our facility (Joint Institute for Nuclear Research in Dubna). The comparison 

has been based on histograms and conformity indices proposed by several 

authors in literature: CIRTOG (Shaw et al. 1993), CN (van’t Riet et al. 1997), 

COIN (Baltas et al. 1998), CIHT (Lomax and Scheib, 2003), and COSI (Menhel 

et al. 2006). Different conformity indices have been calculated for each 

plan. 

Results: For all analyzed cases the calculated indices show a slightly better 

dose distribution for conformal proton plans. The overall mean value of 

CIRTOG for all patients was 1.2 for protons and 1.3 for photons, CIHT: 0.75 

for protons and 0.72 for photons, CN: 0.69 against 0.68 and COIN: 0.67 for 

proton and 0.62 for photon plans (ideal value for all these indices is 1). COSI 

index showed better protection of organs at risk for proton radiation for all 

analyzed organs. This index was calculated for each organ at risk separately, 

and organs at risk were different for each case, thus it was compared for 

each plan individually. Indices of conformity of all plans we prepared were 

in a proposed clinical tolerance range (10.6). 

The indices were calculated on the basis their definition, so they are using 

(except COSI) regions limited by reference isodose. In our case physician 

choose as reference dose 80% of maximum dose. However we can find the 

biggest noticeable difference between proton and photon plans in the lower 

doses region. This difference in dose distributions is not taken into account 

by indices used. The superior conformity or proton therapy dose distribution 

is reproducible for different sites. 

Conclusions: This work confirms that a better conformal distribution can be 

achieved with proton radiotherapy rather than with a photon treatment using 

similar advancement level of delivering system. Nevertheless calculated conformity 

indices we reported for both modalities were similar. It is not possible 

to evaluate the influence of this improvement in dose distribution on clinical 

results. We still have to gather more information about long term follow-up of 

proton-treated patients. 

1379 poster 

EVALUATION OF STEREOTACTIC LIGHT ION RADIATION THERAPY 

REGARDING THE TREATMENT OF LARGE INTRACRANIAL ARTE- 

RIOVENOUS MALFORMATIONS 

B. Andisheh 1 , P. Mavroidis 1 , B. Lind 1 , M. Bitaraf 2 , A. Brahme 1 

1 KAROLINSKA INSTITUTET AND STOCKHOLM UNIVERSITY, Department of 


2 TEHRAN UNIVERSITY OF MEDICAL SCIENCES AND IRAN GAMMA KNIFE 

CENTER, Department of Neurosurgery, Tehran, Iran Islamic Republic of 

Purpose: To make a comparison between the most conventional radiation 

modalities regarding the management of patients with large AVMs. For large 

intracranial arteriovenous malformations (AVMs) not amendable to embolization 

or resection, the special characteristics of high ionization density light 

ion beams offer several advantages over photon and proton beams for high 

dose stereotactic radiation therapy. These advantages include more favorable 

depth dose-distribution in tissue, almost negligible lateral scatter, a sharper 

penumbra, a steep dose fall-off beyond the Bragg peak and a higher probability 

of vascular response. 

Materials: Dose Volume Histograms (DVHs) and peripheral doses for large 

AVMs from different centers were collected and dose-response parameters

were derived by maximum likelihood fitting of the Binomial model to these 

data. The Binomial model is used because the effective number of crucial 

vessels such as large fistulous nidus vessels is low, making the Poisson 

model less suitable. In this study the radiobiological differences between the 

radiation modalities were also taken into account. 

Results: Light ion Bragg peak dose delivery has exactly the precision required 

for treating very large AVMs, as well as for delivering extremely sharp 

focused beams to irregular lesions. A better angiographic obliteration rate as 

well as lower complication rate and lower white matter necrosis for stereotactic 

radiosurgery with light ions was observed, which composed a more 

favorable overall clinical outcome. Also, a sharper dose response gradient 

was observed for patients treated by helium ion beams, which probably is related 

to a more homogenous radiosensitivity of the AVM nidus to ion beam 

radiation, a benefit which is not available for low ionization density radiation 

modalities like photons and protons. 

Conclusions: Bragg peak radiosurgery can be recommended for most large 

and irregular AVMs and for the treatment of lesions located in front of or adjacent 

to sensitive and functionally important brain structures. The unique 

physical and biological characteristics of light ion beams offer considerable 

advantages for the treatment of AVMs and the limitations of conventional radiation 

modalities such as photons and protons may be overcome by a better 

dose and biological effect distribution of the densely ionizing ion beams. For 

AVM sizes of about 10 cm3 Helium to Lithium ions are most suitable and for 

larger AVMs Lithium to carbon ions may be even better. 

1380 poster 

LUMINESCENCE DOSIMETRY IN PROTON THERAPY USING 

FIBER-COUPLED ALUMINUM OXIDE CRYSTALS 

J. Edmund 1 , C. E. Claus Erik Andersen 2 , S. Steffen Greilich 2 

1 



2 

RISØ NATIONAL LABORATORY, TECHNICAL UNIVERSITY OF DENMARK, 

Department of Radiation Research, Roskilde, Denmark 

Purpose: The interest in proton radiotherapy is increasing due to the dosemetric 

advantages of this treatment compared to traditional radiotherapy with 

high energy photons. So far, approximately 40000 patients have been treated 

with proton therapy in 25 facilities worldwide. Here, we look into the potential 

use of aluminum oxide doped with carbon (Al2O3:C) as a dosimeter material 

for treatment verification in proton radiotherapy. 

Materials: Recently, a new dose measuring system containing small (~5 mg) 

Al2O3:C crystals attached to optical fiber cables has been introduced. The 

crystals were irradiated with 10-60 MeV protons corresponding to a linear energy 

transfer (LET) between 4.6 and 1.1 keV/µm in water. After irradiation, an 

optically stimulated luminescence (OSL) signal can be read out by stimulating 

the crystal with light and we used the initial part and the total area of the resulting 

OSL decay curve. We used track structure theory (TST) to predict the 

LET dependence of the OSL signal. In TST, a detector signal is considered to 

be the result of target activation and the signal produced by proton irradiation 

is calculated from a signal produced by gamma irradiation and a radial dose 

distribution around the proton track. 

Results: The figure shows the relative efficiency, η, of the initial OSL signal 

(top panels) and the total OSL area (bottom panels) versus LET in water at 

0.3 Gy (left), 2 Gy (middle) and 5 Gy (right). The open circles are the experimental 

data and the solid lines are the TST calculations. Experimentally, we 

observed that the initial OSL signal was independent of LET for all energies 

at 0.3 Gy but not at higher doses. The total OSL area showed an LET dependent 

behavior at all doses and energies. The TST calculations are in good 

agreement with the experimental data except for the initial OSL signal at 0.3 

PHYSICS AND TECHNOLOGY : PROTONS AND IONS 

S 439 

Gy where the efficiency is overestimated. On the basis of TST, we estimate 

a socalled "target radius" to be between 30 and 150 nm and associated this 

radius with a charge migration distance in the crystal. 

Conclusions: Although several assumptions were introduced in the calculations, 

we found that TST can qualitatively account for all the main features 

of the experimental data. From these calculations, the initial OSL signal is, 

in general, LET dependent which makes Al2O3:C unsuitable for OSL proton 

dosimetry. The initial OSL signal can, however, be combined with the total 

OSL signal to provide an LET independent response for a given dose and 

LET interval. 

1381 poster 

PARAMETERIZATION AND APPLICATION OF KERNELS FOR 

MODELING SCANNED PROTON BEAM COLLIMATOR SCATTER 

DOSE 

E. Traneus 1 , A. Ahnesjö 2 , N. Tilly 1 , P. Kimstrand 1 


2 AKADEMISKA SJUKHUSET, Department of Oncology, Radiology and 

Clinical Immunology, Uppsala, Sweden 

Purpose: Collimators are routinely used in proton radiotherapy to define the 

field and to improve the penumbra. However, a collimator will inevitably produce 

scattered protons that will reach the patient. This scatter dose may 

contribute up to 15% of the local dose and should be included during treatment 

planning. We present a method, based on compact parameterizations 

of Monte Carlo generated reference kernels, for a fast reconstruction of the 

phase space of collimator scattered protons. 

Materials: We consider out-scatter following incidence on either the inner 

edge (i.e. upstream) surface, or the front face surface of a tungsten collimator. 

A set of reference kernels differential in out-scatter energy and direction were 

calculated for a range of incidence conditions by the Geant4.8.2 code. The 

kernels were then used to numerically construct a sequence of probability 

density functions which were integrated and inverted. The inverted functions 

were parameterized yielding a compact representation from which out-scatter 

events can be sampled using three random numbers and evaluations of a 

few exponentials and polynomials. A set of out-scatter phase spaces was 

compared to full Geant4 simulations. Water dose distributions from MLCcollimated 

proton fields were calculated using a full MC of the MLC transport 

and by a transport using the kernels of this work. Output factors (Gy/MU) 

along the central axis for rectangular tungsten apertures were measured at 

the The Svedberg Laboratory scanned proton beam line for energies 98 MeV 

and 180 MeV and compared to calculations using out-scatter sampled according 

to the method of this work. 

Results: Comparisons of dose profiles for MLC collimated fields calculated 

using a full simulation of the transport in the MLC and by sampling out-scatter 

using the kernel parameterizations of this work show excellent agreement 

(see Figure). A speed gain of the MLC transport of about 400 times is obtained 

compared to full Geant4 MLC simulation of the MLC geometry. The 

parameterization yields a compact kernel representation using less than 2 kb 

of data (450 floats) per collimating material. The figure shows dose profiles 

in water (180 MeV, 5 cm air gap, depth 5.9 cm, leaf width 1 cm) for a comb 

field shaped by a 5 cm thick tungsten MLC. Solid line: this work, dashed line: 

full MLC simulation. TOT= total dose, FF = front face scatter dose, IE = inner 

edge scatter dose. 

Conclusions: A fast and compact method was developed to model collimator 

out-scatter. We report validation calculations and measurements for a collimated 

scanned proton beam. The current realization focuses on MC based 

in-patient dose calculations. Work is on-going to apply the same methodology 

to analytical dose engines (i.e. pencil beam) and to parameterize out-scatter 

of other materials such as brass, Cerrobend and Roses metal which are commonly 

used as apertures for passively scattered beams.

S 440 PHYSICS AND TECHNOLOGY : PROTONS AND IONS 

1382 poster 

PROTON DOSIMETRY: REAL-TIME LUMINESCENCE SYSTEMS IN 

A CLINICAL SET-UP 

S. Greilich 1 , C. E. Andersen 1 , E. Grusell 2 , S. Mattsson 3 

1 

RISØ NATIONAL LABORATORY FOR SUSTAINABLE ENERGY, TECHNICAL 

UNIVERSITY OF DENMARK, Department of Radiation Research, Roskillde, 

Denmark 

2 

UPPSALA UNIVERSITY HOSPITAL, Department of Hospital Physics, 

Uppsala, Sweden 

3 



Purpose: The aim of this study was to test materials for luminescence-based, 

all-optical dosimetry systems [1,2] that are developed and evaluated for online 

QA (quality assurance) in clinical proton beams. Because of their small size 

(few mm 3 ), the detectors used in these systems can also serve as tools for 

vivo dosimetry. Even beam quality information might be available due to their 

reponse being LET dependent. 

Materials: The radioluminescence (RL) from fibre-coupled Al2O3:C crystals 

and the fluorescence signal from a BCF-12 organic scintillator were investigated 

while scanning the Bragg curve in a water phantom of the unmodulated 

175 MeV narrow beam line at the The Svedberg Laboratory (TSL) in Uppsala, 

Sweden. As shown earlier [3], sensitivity changes make it difficult to use the 

RL signal from unconditioned Al2O3:C detectors for dose-rate measurements 

directly. Therefore, we used a fully saturated crystal for the studies described 

here. As reference, additional dosimetry was carried out using a p-doped 

Si-diode detector. Information on the LET spectra was obtained from simulations 

of the radiation field using the Monte-Carlo transport codes PETRA [4] 

and GEANT4. 

Results: The detectors reproduced the shape of the Bragg curve (see Figure). 

Both served equally well for online monitoring of the dose-rate in the 

low-LET plateau region. Due to their high sensitivity, the impact of counting 

statistics is small - variation in the data reflects fluctuations from the accelerator. 

In the peak region, however, the LET dependence led to a characteristic 

underresponse compared to the Si diode. The peak-to-plateau ratios for the 

diode, BCF-12, and Al2O3:C were 3.3, 2.5, and 1.9, respectively, yielding an 

underresponse in the peak of 0.75 (BCF-12) and 0.60 (Al2O3:C), the latter in 

agreement with previous results [3]. 

Conclusions: Both materials tested were found to be suitable for online 

monitoring systems of the dose-rate and despite their underresponse in 

this region also for fast localisation of the Bragg peak. We favour the organic 

scintillator in this context since no special conditioning of the detector 

is necessary. When trying to find the exact position of the peak, however, 

it should be kept in mind that the LET dependence might shift the apparent 

peak to lower depths. References: [1] Aznar, M.C., Andersen, C.E., 

Btter-Jensen, L., B, S.J., Mattsson, S., KjKristoffersen, F., and Joakim Medin, 

2004, Real-time optical-fibre luminescence dosimetry for radiotherapy: physical 

characteristics and applications in photon beams, Phys. Med. Biol. 49, 

16551669. [2] Beierholm, A.R., Andersen, C.E., Lindvold, L.R., KjKristoffersen, 

F., and Medin, J., A comparison of BCF-12 organic scintillators and 

Al2O3:C crystals for real-time medical dosimetry, Radiation Measurements, 

in press, doi:10.1016/j.radmeas.2007.12.032. [3] Andersen, C.E., Edmund, 

J.M., Medin, J., Grusell, E., Jain, M., Mattsson, S., 2007, Medical proton 

dosimetry using radioluminescence from aluminium oxide crystals attached 

to optical-fiber cables, Nucl. Instr. Meth. A 580, 466-468. [4] Medin, J., and 

Andreo, P., 1997, Monte Carlo calculated stopping-power ratios water/air for 

clinical proton dosimetry (50-250 MeV), Phys. Med. Biol. 42, 89-105. 

1383 poster 

SECONDARY NEUTRON PRODUCTION FROM PATIENTS DURING 

THERAPY WITH HADRONS AND THEIR CORRESPONDING RADIA- 

TION DOSES: ARE THERE POTENTIAL RISKS? 

M. A. Chaudhri 1 

1 KLINIKUM NÜRNBERG-SÜD, Institute für Radiologie, Nürnberg, Germany 

Purpose: To estimate the fluence and energy distribution of secondary neutrons 

produced in patients during therapy with hadrons, and further assess 

their radiation contributions to various organs. There is no reliable data on 

this important subject. 

Materials: In the absence of any reliable experimental or theoretical data on 

the production of neutrons from patient/tissues we chose to make use of the 

existing experimental neutron out put measurements from thick-targets of different 

elements, in order to compute the fluence and the energy distribution of 

the secondary neutrons from human tissue under bombarded with hadrons. 

Then, using the existing tabulations, we calculated the doses to different body 

organs due to these secondary neutrons. 

Results: Our results indicate that at least 4.2 neutrons , with energies greater 

than 5 MeV ,are produced for every carbon ion of 400 MeV / u energy incident 

on tissue. This number reduces to 3, 1.4 and 0.3 respectively at carbon 

energies of 300, 200 and 100 MeV /u.. In the case of neon ions these figures 

are slightly higher. For irradiation with alpha particles the number of these 

secondary neutrons reduces to about 1 neutron per alpha particle with incident 

energy of 200 MeV / u. In the case of protons the numbers of secondary 

neutrons from tissue are estimated to be 0.05, 0.2 and 0.4 per proton of energies 

100, 200 and 300 MeV respectively. There would, no doubt, be even 

more neutrons with energies lesser than 5 MeV which could not be estimated 

due to the lack of experimental data. For a physical treatment C-ion dose of 

20 Gy in the Bragg Peak, the total number of secondary neutrons produced 

in patients are 1.6 x 10 9 / cm 2, 7.3 x 10 8 / cm 2, 2.5 x 10 8 / cm 2 and 

4,1 x 10 7 / cm 2 respectively at carbon-ions energies of 400,. 300, 200 and 

100 MeV / u. These figures for a physical proton dose of 20 Gy in the Bragg 

Peak are 2 x 10 9/cm 2, 4.17 x 10 8 / cm 2 and 4.17 x 10 7 / cm 2 neutrons 

respectively at proton energies of 20, 160 and 70 MeV. The corresponding 

doses to various organs, lying close to the treatment sites, could be as high 

as around 200 mGy for C-ions of 400 MeV/u and protons of 200 MeV/u.. 

Conclusions: In our opinion the large number of secondary neutrons produced 

from patients during therapy with hadrons, and their corresponding 

doses to various organs, indicate they could have real potential to cause new 

primary cancers and cause other harmful side-effects in patients. 

1384 poster 

STATUS OF THE HEIDELBERG ION-BEAM THERAPY CENTRE 

M. Ellerbrock 1 , O. Jäkel 1 , P. Heeg 1 , B. Ackermann 1 , M. Winter 1 , K. 

Parodi 1 , S. Brons 1 

1 HEIDELBERG ION-BEAM THERAPY CENTRE, Medical Physics, Heidelberg, 

Germany 

Purpose: The Heidelberg Ion-Beam Therapy (HIT) Centre is being installed 

at the Department of Radiation Oncology of the University Hospital. The 

facility offers two fixed, horizontal beam lines and one isocentric gantry for 

patient irradiation. Using the magnetic beam scanning technique with active 

energy variation, the HIT machine provides ions from protons to oxygen at 

therapeutic energies to reach depths of up to 30 cm in tissue. To ensure 

efficient patient irradiation, the accelerator allows for fast switching of energies 

and ion species. The patient positioning is based on robotic couch and 

robotic imaging systems. The main purpose of the facility is to evaluate the 

clinical potential of heavy ion beams as compared to proton and conventional 

radiotherapy in clinical trials. The current status of the HIT Centre will be

PHYSICS AND TECHNOLOGY : TREATMENT TECHNIQUES, MODALITIES AND TECHNOLOGY 

presented, focussing on the quality assurance (QA) system and discussing 

some results of the clinical commissioning of the facility. 

Materials: The QA system of the HIT facility is based on the experience 

gained from carbon ion radiotherapy at the German pilot project for heavy ion 

therapy at the Gesellschaft fr Schwerionenforschung (GSI) in Darmstadt and 

has been optimized to allow safe and efficient clinical operation. It consists 

of commissioning procedures, acceptance tests and constancy tests for the 

complete workflow, including patient imaging, treatment planning, plan verification, 

patient positioning, treatment delivery, and safety and control systems. 

Results: A complete QA system has been worked out and is presently being 

implemented at the HIT Centre. Basic beam parameters for proton and 

carbon ion beams have been measured in the horizontal treatment rooms, 

demonstrating the flexibility and reliability of the accelerator machine for efficient 

beam delivery. Currently the raster scanning and beam monitoring 

systems are being commissioned. Pre-clinical operation is expected to start 

in June 2008, while first patient treatment with the horizontal beams is scheduled 

for fall 2008. Patient therapy at the gantry will start in summer 2009. 

Conclusions: The clinical commissioning of the HIT Centre has started and 

will continue throughout spring and summer this year. Clinical operation is 

scheduled to start in fall 2008 and will allow for the first time to evaluate the 

clinical potential of a scanned beam of heavy ions in direct comparison to 

proton and conventional radiotherapy in clinical trials. 

Physics and technology : Treatment 

techniques, modalities and 

technology 

1385 poster 

3-D CT PLANNING FOR INTERNAL MAMMARY NODES IRRADIA- 

TION 

D. Ozturk 1 , S. Yondem 1 

1 MEDICAL PARK HOSPITAL, Radiation Oncology, Istanbul, Turkey 

Purpose: Methods for IMN irradiation are wide tangents, standart tangents 

with separate AP field mixed photon/electrons to the IMN or standart tangents 

with oblique field mixed photon/electrons to the IMN. With the enhanced use 

of 3D-CT-based treatment planning, the body of knowledge forces the radiation 

oncologist to take into account the dose heterogeneities in the junction 

of the medial tangent and IM field and the possible side effects without being 

sure of effectiveness of this kind of irradiation.The purpose of this study 

is to compare the conformal technique with standart field irradiation in terms 

of covering adequately IMN and breast/chest wall, reducing the dose to the 

heart and having more homogenous irradiation 

Materials: Target volumes and organs at risk were delineated on CT scans 

of ten patients with left-sided breast cancer. 3D conformal technique uses 

oblique field angled to a given degree to be able to produce the more homogeneous 

coverage of IMN nodes and breast. The medial edge of MI field was 

not allowed to be more than 3 cm away from midline to reduce the dose to 

the contralateral breast. Doses of lungs and heart are limited to V20 < 25% 

and V30< 10% respectively. 

Results: Using conformal oblique field causes small increase in lung dose, 

better target coverage and more homogenous dose distribution. The table 

shows the comparison between two technique in terms of PTV coverage and 

normal tissue doses. 

Conclusions: The conformal oblique technique allowed us significantly more 

homogenous dose distribution and acceptable doses to OARs. 

1386 poster 

S 441 

ACCELERATED PARTIAL BREAST IRRADIATION WITH BRT HDR: 

ROLE OF MULTIMODALITY IMAGES IN IMPLANT RECONSTRUC- 

TION 

S. Gribaudo 1 , V. Richetto 1 , A. Urgesi 1 , E. Madon 1 , A. Sardo 1 , E. 

Roberto 1 

1 AO OIRM-S. ANNA, Radiotherapy, Turin, Italy 

Purpose: The trend in the management of patients with breast cancer, over 

the last 20 years, has been to reduce the extent of treatment without limiting 

its effectiveness. It has been recently proposed the technique of accelerated 

partial breast irradiation (APBI) instead of the whole breast irradiation 

based on the observation that most breast cancer are limited to one quadrant 

or to a small area of the breast. The identification of this sub-group of patients 

with breast carcinoma with limited extent (BCLE), was made possible 

by applying optimal quality mammography and by the meticulous pathological 

assessment of the surgical specimen; approximately 50% of invasive ductal 

carcinomas could have limited extent and these BCLE could be the potential 

candidates for the treatment of surgical excision of the tumour followed by 

APBI. 

Materials: Since 1997 35 patients were treated with interstitial implants and 

12 patients were treated with Mammosite implants (2004-2007). To optimize 

brachiterapy planning, multimodality images are used in implants reconstruction. 

Digital radiographic images offer a better spatial resoluction in implant 

reconstruction, while TC images give better information on patients anatomy. 

A specific homemade phantom has been used to check goodness verification 

in implant reconstruction on TC images and digital RX with Plato algorithm 

BPS14.2.6; examination correlation between implant on the same phantom 

reconstructed on RX and transferred to TC images has been tested with Plato 

BPS Insight 14.2. Brachithrapy planning on 20 patients is performed on TC 

images with implants reconstruction based on correlated digital radiographic 

images: radiobiological and physical evaluation can be done on each brachitherapy 

plan. 

Results: A comparison between BRT planning on multimodality images and 

BRT planning simulated on CT images have been performed using EUD 

calculation and dose homogeneity measurements. Also dose volume histograms 

have been evaluated on target and on organ at risk. Specific points 

related on implant have been compared in coordinates and dose.Significant 

differences were found in dose point coordinates and relative distances from 

the two reconstruction method compared. 

Conclusions: These differences does not mean that the distribution of the 

dose is really so different EUD, mean dose and dose volume histogram on 

organ at risk don’t show the same differences. The most important effect 

observed is a translation of the whole implant from digital RX reconstruction 

to TC reconstruction giving different values of minimum and maximum dose 

in target volume. 

1387 poster 

AUTOMATIC SEED LOCALIZATION IN RADIOGRAPHS 

F. A. Siebert 1 , M. Hirt 1 

1 UKSH, CAMPUS KIEL, Clinic of Radiotherapy, Kiel, Germany 

Purpose: Three-dimensional reconstruction of permanent seed implants is 

very accurate using a set of three radiographs. Different algorithms exist 

to calculate the 3D seed distribution with films. Most of these methods require 

manual seed detection in the radiographs before the reconstruction itself. 

This study presents a robust automated algorithm to detect not only the 

seed center but also their orientation on the radiographic film. This provides 

more information for the reconstruction algorithm and knowledge of the tilting 

of the sources. 

Materials: Between three and six digital radiographs (Fuji FCR) were taken 

from each patient 1-2 hours after the implant of the loose Iodine-125 seeds 

(IsoSeed S17, Bebig) in different angles (typically 0 and ±25 degree). The 

digital DICOM films were converted to 8-bit tiff-datasets. A dedicated segmentation 

routine for the image processing software ImageJ (version 1.39) 

was developed. This routine contains several image processing steps to detect 

the seeds in the radiographs. At first the contrast in the radiograph is 

enhanced, followed by a background removal filter. After an automatic threshold 

calculation of the image a segmentation algorithm detects single seeds 

in the image. For this the algorithms assumes an oval seed form of 4.5mm 

length maximum. Often seeds are overlapping in their projections and thus 

are clustered in the radiograph. To localize these sources a cluster algorithm 

is able to detect most clustered seeds.For this study we investigated 58 films 

of 11 different implanted patients. The number and positions of the automatically 

detected sources were recorded and compared to manual results of one 

observer. 

Results: The algorithm found in mean (±standard deviation) 44.0 (±10.5) 

seeds per radiograph, the observer 46.1 (±11.2). In mean 92% of the 

seeds could be correctly detected by the presented automated method. Only 

8% were falsely detected, mostly false-negative, i.e. they were left out. A 

closer inspection showed that especially clustered seeds were difficult to define.Time 

consumption of the detection depends on the number of seeds and

S 442 PHYSICS AND TECHNOLOGY : TREATMENT TECHNIQUES, MODALITIES AND TECHNOLOGY 

seed clusters. It varied between 15 and 30 s per radiograph. 

Conclusions: A novel approach for automatic seed detection in radiographs 

was developed. For the used seed type and digital radiograph system it 

shows a good reliability to detect sources automatically. Nevertheless results 

must be manually reviewed by an operator. The presented system is in clinical 

use for post-planning of permanent Iodine-125 implants of the prostate. 

1388 poster 

CHANGES IN SEX HORMONE PROFILE AND TESTS DOSES DUE 

TO PELVIC IRRADIATION IN RECTAL CANCER PATIENTS TREATED 

WITH DIFFERENT IRRADIATION MACHINES 

A. Ameri 1 , M. Sobhani 1 , K. Sheibani 1 , A. Alidoosti 1 

1 IMAM HOSSEIN HOSPITAL, Radiation Oncology, Tehran, Iran Islamic 

Republic of 

Purpose: Sexual complications of pelvic irradiation have gained more attention 

because of increased survival of patients. Co60 teletherapy has wide 

penumbra so can cause more testes doses during radiotherapy in vicinity of 

lower border of pelvic portals when treated for rectal cancer. In this study we 

compared testicular doses when pelvis is irradiated for rectal cancer with two 

different machines and its effect on sex hormones level. 

Materials: This is a cohort study. Rectal cancer patients treated by pelvic 

irradiation concomitant with chemotherapy in two groups. Group I treated by 

Co 60 teletherapy and group II by linear accelerator (LINAC). Patients with 

sexual dysfunction or any sexual complain, history of endocrine disease and 

abdomino pelvic resection for cancer surgery were excluded. Testes doses 

were measured by TLD (LiF), three times during whole course of irradiation 

in 5 patients of each group. Sex hormones level were measured immediately 

before and 3 to 6 week after completion of irradiation. T test and Mann 

Whitney Test were used to compare data. 

Results: 28 patients were enrolled. Two died early in course of radiotherapy 

(one in each group)and one patient excluded because his testes were 

inside of treatment portals. Patient’s and disease characteristics were similar 

between two groups. Mean testes dose in patients treated by LINAC 

(55±24.7mGy) was significantly lower than Co60 (120±23mGY) with a P 

value less than 0.001. Serum FSH and LH level increased after irradiation 

in two groups and there is no relation between FSH and LH changes with 

treatment machines(P=0.2, P=0.6 respectively). Serum level of testosterone 

decreased significantly in patients treated by Co60(P


risk (OAR and PRV) corresponding to "conventional" treatment was achieved 

after a supplementary CT scan performed in a prone position. Three mm 

margins were used for Brain and cranial structures (as PTV brain, intracranial 

PRV structures) and 5 mm margins were used for infracranial structures (as 

PTV spine, or cervical and abdominal PRV structures). 

Results: Feasibility of daily positioning with 3 and 5 mm margins was realized 

in patient settled up in a comfortable and reproducible supine position. 

The clinical tolerance was good except for one patient who needed a ten 

days treatment interruption for a grade 3 aplasia. Concerning dose distribution 

of craniospinal axis irradiation, an advantage of the helical tomotherapy 

technique was slightly observed for the PTV-Brain and PTV-Spine (with max 

doses average superior to 3.2 Gy and mean doses superior to 1 Gy observed 

with the conventional techniques to reach the same prescribed dose). An 

important sparing was observed for 10 extra-cranial evaluated OAR as, for 

instance, thyroid (max dose average 13 Gy vs 22.5 Gy and mean dose average: 

9.2 Gy vs 21.1 Gy), oesophagus (max dose average 13 Gy vs 35 Gy 

and mean dose average: 11.4 Gy vs 33.5 Gy), heart (max dose average 10.5 

Gy vs 22.5 Gy and mean dose average:7.2 Gy vs 17.9 Gy), bowel (mas dose 

average 17 Gy vs 31.5 Gy and mean dose average: 8.3 vs 13.1 Gy). 

Conclusions: Initial experience demonstrates the feasibility of the helical tomotherapy 

technique for craniospinal irradiation of the adult. Tomotherapy improves 

dose ratios over conventional radiation for the PTV volume and most 

organs at risk. Other patients are being studied to confirm our results. Furthermore, 

a long-term follow-up is necessary to analyze the impact of low 

dose irradiation in a large volume. 

1392 poster 

DECREASED DOSE TO THE RECTUM DURING PHOTON BOOST 

THERAPY OF THE PROSTATE 

K. Nilsson 1 , U. Isacsson 2 , S. Asplund 1 , E. Morhed 2 , I. Turesson 1 

1 DEPARTMENT OF ONCOLOGY, RADIOLOGY AND CLINICAL IMMUNOLOGY, 

UPPSALA UNIVERSITY, Department of Oncology, Akademiska Sjukhuset, 

Uppsala, Sweden 

2 DEPARTMENT OF ONCOLOGY, RADIOLOGY AND CLINICAL IMMUNOLOGY, 

UPPSALA UNIVERSITY, Department of Hospital Physics, Akademiska 

Sjukhuset, Uppsala, Sweden 

Purpose: Curative treatment of localized prostate cancer with radiotherapy 

demands high doses. Dose escalation with IGRT is often used or a combination 

of 3D conformal radiotherapy with either brachy therapy or proton 

therapy. The proximity between the prostate and rectum often leads to a 

compromise between dose to target and organ at risk. The positioning of the 

prostate during radiotherapy is also a problem, since the prostate is known 

to be a movable organ. The present study describes a method where the 

distance between the prostate and rectum is increased during boost therapy 

with photons by retraction of the rectum in dorsal direction. 

Materials: Ten patients with biopsy proven, localized adenocarcinoma of the 

prostate were studied. The patients received 2-3 gold markers in the prostate, 

which were spread out in the prostate in order to ensure a satisfying 3D positioning. 

The patients were immobilized in a special fixation couch, and a cylindrical 

rod of Perspex was inserted into the rectum. This device is allowing the 

rectum to be retracted dorsally in order to maximize the separation between 

the prostate gland and the rectum wall. Each day of the photon boost treatment, 

the prostate was positioned using anterior-posterior and lateral portal 

images visualising the gold markers in the prostate. The positioning was done 

with an accuracy of less than 3 mm. Two comparative treatment plans were 

made. The first with 3D conformal photon radiotherapy to a dose of 50 Gy 

in 25 fractions of 2 Gy and with an additional photon boost of 20 Gy in four 

fractions of 5 Gy with retraction of the rectum. The other treatment plan was 

made with the same fractionation but planned with IMRT technique without 

retraction of the rectum. 

Results: Comparative treatment planning shows that the treatment plans 

with the rectal rod reduces the rectal volume receiving more than a dose 

corresponding to 70 Gy in 2 Gy fractions compared to the IMRT plans. 

Conclusions: Retraction of rectum during 3D conformal treatment decreases 

the dose to rectum compared to IMRT. 

1393 poster 

DESIGN OF A SIMPLE MRI VISIBLE CATHETERS IN GYNAECO- 

LOGICAL BRACHYTHERAPY 

J. Perez-Calatayud 1 , F. Kuipers 2 , F. Ballester 3 , D. Granero 1 , J. Richart 4 , 

S. Rodriguez 4 , M. Santos 4 , A. Tormo 1 , M. C. Pujades 1 

1 LA FE UNIVERSITY HOSPITAL, Radiation Oncology, Valencia, Spain 

2 NUCLETRON B.V., Veenendaal, Netherlands 

3 UNIVERSITY OF VALENCIA-IFIC, Valencia, Spain 

4 CLINICA BENIDORM HOSPITAL, Radiation Oncology, Benidorm, Spain 

Purpose: In recent years the clinical dosimetry in cervix brachytherapy is 

moving clearly towards 3D image based treatment planning, according the 

gynaecological GEC-ESTRO (Haie-Meder 2005, Ptter 2006). MRI is needed 

with preferred modality of T2 weighted. One of the most used applicators 

S 443 

is the CT-MR compatible tandem plus colpostats (T/C) (Nucletron, Veenendaal, 

The Netherlands). The main disadvantage of MRI is the lack of dummy 

catheters. Therefore an additional imaging modality is usually required. By 

other hand, one disadvantage in sliced based reconstruction is that resolution 

in sagittal directions can be affected by the slice thickness. The objective of 

this study is the presentation of a modified applicator in which the catheter 

visibility is significantly improved with a relative common available material. 

In addition, a simple methodology is presented that solves the problem of 

sagittal uncertainties. 

Materials: In this work, a modification to the existing T/C applicator has been 

made available increasing the entrance catheter hole. This modification allows 

a greater dummy catheter diameter and consequently allows filling it with 

more material per unit length. Visibility was studied with this new applicator 

using 6F plastic catheters filled with different materials: Gd-157 in different 

concentrations, vegetable oil, A-vitamin, solid plastic and saline water. On 

the 1.5T MRI scanner, different sequences and settings have been studied. 

Also geometrical distorsion is studied with phantoms and with CT-MRI fusion 

patient images. 

Results: The catheter filled with saline water (0.9% NaCl) plus iodine compound 

was clearly seen in both axial and sagittal T2 acquisitions together 

with a very good contrast that allows following it clearly along the slices for 

TPS reconstruction. To avoid uncertainties introduced by the slice thickness, 

a simple procedure is presented: In the sagittal set, the distance from the first 

slice centre to the deeper fluid position can be easily obtained, it is traslated to 

the axial set using the offset utility on PLATO TPS. No geometric deformation 

was observed with phantoms and also when comparing inter bone distances 

for patient images based on CT-MRI fusion. 

Conclusions: A modified tandem/colpostats applicator plus catheter is presented 

for which the T2 weighted MRI catheter visibility is highly improved 

with saline water a very simple and accessible material. With respect to the 

previous studies in the literature about MRI catheter visibility, the method proposed 

in this work allows a very powerful signal less dependent of specific 

MRI conditions. Also, a method is proposed to solve the problem of the uncertainty 

derived from slice thickness using few sagittal acquisitions around 

the implanted applicator. Both improvements allow users to perform a MRI 

T2 weighted, only based planning, in a fast and simple way. 

1394 poster 

DOSIMETRIC CHARACTERISTICS OF A NEW CONTACT X RAYS 50 

KV MACHINE "PAPILLON 50" 

S. Marcié 1 , J. McCaron 2 , J. P. Gerard 1 

1 CENTRE ANTOINE-LACASSAGNE, Radiotherapie, Nice, France 

2 ARIANE MEDICAL SYSTEM, Nottingham, United Kingdom 

Purpose: The old contact therapy unit RT50 R○from Philips is not anymore 

manufactured. A new machine, "Papillon50TM", will be commercialised in 

April 2008. Measurements were performed on a prototype. We present the 

comparison of the 2 machines measurements. 

Materials: The new machine produces 20 to 50 kV X rays. Features of this 

machine are an integrated computer, record of the treatment, safety keys, 

fibroscop to see the lesion. The tube diameter is 1.7 cm instead of 3 cm on 

the old machine. Different kind of applicators are available but with different 

FSD. Parallel plate ionisation chamber and Gafchromics R○films were used 

for measurements and calibration. A large volume chamber was used for 

radioprotection measurements. 

Results: With the 3 cm applicator, 50 kV and 2.5 mm Al, the HVL is greater 

than the old one (0.7 vs 0.5 mm) and the depth of the 50% isodose is deeper 

(6 vs 4 mm). For a 3 cm diameter applicator, the dose rate is lower (11 vs 20 

Gy/ min). Radiation leakage is inferior to 1 mGy but the scattered radiation 

by the phantom is greater (at 1 m, 133 vs 10 YSv). 

Conclusions: The new "Papillon50TM" machine appears to reproduce most 

of the dosimetric characteristics of the Philips Rt50. It has some specific 

advantages, an X ray tube of smaller diameter, a computer, an on line imaging 

of the treated area. For all these reasons, a new impulse is expected for 

contact X rays 50 kV for some specific clinical indications in the coming years. 

1395 poster 

DOSIMETRIC COMPARISON OF THREE-DIMENSIONAL CONFOR- 

MAL RADIOTHERAPY AND INTERSTITIAL BRACHYTHERAPY FOR 

PARTIAL BREAST IRRADIATION, AND WHOLE BREAST EXTERNAL 

BEAM IRRADIATION 

T. Major 1 , G. Fröhlich 1 , L. Jánváry 1 , C. Polgár 1 , J. Fodor 1 


Purpose: To compare dosimetrically two partial breast irradiation techniques 

and whole breast irradiation focusing on dose to organs at risk. 

Materials: Partial breast irradiation (PBI) was applied for eight patients with 

3D conformal external radiotherapy (3D-CRT). All patients were treated for 

early stage breast cancer in 2007. In addition, plans for whole breast irradiations 

(WBI) were made for the same patients and outlined structures. Furthermore, 

eight patients treated with interstitial brachytherapy (IBT) for PBI were


selected for the study. For plan evaluations dose-volume histogram analysis 

was performed. Relative volumes in percentage (Vxx) receiving a specified 

dose related to the prescribed dose (xx %) and relative doses (Dyy) irradiating 

a given fraction of the organ (yy %) were calculated and compared. Maximal 

doses to the lung and heart were also determined. 

Results: The mean PTV was 162.6 cm3 and 64.4 cm3 (p

1399 poster 


EVALUATION OF PHOTON BEAMS WITHOUT FLATTENING FILTER 

(FFF): MEASURED VERSUS CALCULATED DOSE DISTRIBUTIONS 

H. Riem 1 , A. Van Esch 2 , L. Tillikainen 3 , T. Torsti 4 , D. Huyskens 2 , M. 

Rusanen 4 , S. Siljamäki 4 

1 

VARIAN MEDICAL SYSTEMS INTERNATIONAL AG, Department of Image 

Processing and Research, Baden-Daettwil, Switzerland 

2 

7SIGMA AND CLINIQUE STE ELISABETH, NAMUR, Tildonk, Belgium 

3 

VARIAN MEDICAL SYSTEMS, Department of Research and Development, 

Palo Alto CA, USA 

4 

VARIAN MEDICAL SYSTEMS FINLAND, Department of Research and 

Development, Helsinki, Finland 

Purpose: Removing the flattening filter from a treatment beam considerably 

increases the final machine output. This could be beneficial for stereotactic 

treatments and/or gated treatments, where shortening of the beam-on time 

per treatment field represents a significant advantage. However the clockshaped 

profile and the different energy distribution of these beams represent 

a new challenge for treatment planning systems. This study investigates the 

accuracy of the AAA photon dose calculation algorithm modified for the flattening 

filter free (FFF) mode for static and IMRT fields. 

Materials: Basic beam data (beam profiles, depth dose curves and output 

factors) were acquired to allow the configuration of the photon dose calculation 

algorithms in Eclipse (focussing on AAA and on the dose volume optimizer). 

To assess the accuracy of the dose calculation algorithm calculations 

were performed with a non-clinical research version of AAA, adapted for the 

FFF mode. Planar dose data were calculated and measured with the Seven 

29 2D array (PTW) sandwiched between solid water plates in a 6MV and 

18MV photon beam in service mode (the flattening filter was replaced by a 

flat -0.8 mm thick- brass plate) of an iX Trilogy. Symmetric, asymmetric and 

IMRT fields were delivered. The latter encompassed artificial test plans as 

well clinical IMRT fields. 

Results: For the acquisition of the basic data, precise centering of the beam 

was of paramount importance. All static symmetric fields were within ~2%, 

2mm. Somewhat inferior results were obtained for the highly asymmetric 

open fields (up to ~4 %, 2mm). Similar results were found for the IMRT fields 

with symmetric or highly asymmetric collimator settings, respectively. 

Conclusions: The adaptation of AAA for the FFF mode and the experimental 

verification provided first insights for its future use in clinic: preliminary 

results are satisfactory (for both 6MV and 18MV), especially for symmetric 

fields. Further fine-tuning will focus on the optimisation of the second source 

to improve results for asymmetric fields. 

1400 poster 

EXPERIMENTAL AND SIMULATION VERIFICATION OF THE 

ELECTRON CONTAMINATION DURING HIGH ENERGY SCANNED 

PHOTON BEAM IMRT 

B. Andreassen 1 , S. Strååt 1 , R. Holmberg 2 , A. Brahme 2 , P. Näfstadius 3 

1 

STOCKHOLM UNIVERSITY, KAROLINSKA INSTITUTET, Medical Radiation 


2 

KAROLINSKA INSTITUTET, Medical Radiation Physics, Stockholm, Sweden 

3 


Sweden 

Purpose: With high energy scanned photon beams in combination with static 

or dynamic multi leaf collimation for IMRT dose delivery the treatment time 

can be reduced with an improved clinical outcome compared to a normal 

IRMT treatment [R Svensson et al Med Phys 25 2358-2369 (1998)]. This is 

also the method of choice for PET-CT imaging of the induced activity as it 

gives a high PET-yield signal closely proportional to the photon fluence distribution. 

Scanned narrow high energy photon beams can be produced by 

directing a high energy electron beam onto a thin metallic target. The composition 

and thickness of this target determines the energy spectrum, forward 

S 445 

yield and FWHM of the brehmsstrahlung beam. The transmitted electron 

beam, which has lost little of its energy, must be safely deflected by a magnet 

placed downstream of the target. The composition of the target determines 

the angular and spatial spread of the transmitted electron beam and here 

we have studied the effect of transmitted high energy electrons with a large 

angular spread. 

Materials: The experimental work was performed with the 50MeV racetrack 

microtron at Karolinska University hospital. The treatment head was modified 

to accommodate the use of scanned narrow photon beams and the block 

collimators in combination with the multileaf collimators was used as a electron 

collector for the transmitted high energy electron beam. The composition 

of the brehmsstrahlung beam was examined both experimentally and by 

simulations using a combination of a FEM magnetostatic simulation software 

(Opera3D/Tosca) and Monte Carlo software (Geant4). To have a homogenous 

dose over a larger area we used this beam with an inverse planning 

program and then implemented the resulting scanning pattern. 

Results: The measured beam profile from a 3mmBe target 100mm into water 

at isocentre (SID 100cm) had a FWHM of 34mm and contained an overlapping 

exponentially decreasing dose contribution from transmitted energy 

electrons with a maximum contribution of about 2% compared to the maximum 

photon dose. Using this beam to create a larger area with homogenous 

dose allowed us to study the accumulative effect of the transmitted electron 

tail both inside and outside of the targeted area. 

Conclusions: The angular and spatial spread as well as the energy composition 

of the transmitted electron beam are important factors when implementing 

an system for scanned narrow photon beams. Transmitted electrons 

with a large angular spread and with retained energy can contribute to the 

delivered dose. 

1401 poster 

FAST RADIOTHERAPY TREATMENT FOR ANAL CANCER WITH 

VMAT 

F. Stieler 1 , D. Wolff 1 , F. Lohr 1 , V. Steil 1 , Y. Abo-Madyan 1 , F. Wenz 1 , S. 

Mai 1 

1 UNIVERSITY MEDICAL CENTER MANNHEIM, Department of Radiation 

Oncology, Mannheim, Germany 

Purpose: The shielding of organs at risk (OAR) like testis, small bowel and 

bladder increases the complexity of a treatment for anal cancer. One possibility 

to solve this problem is step and shoot intensity modulated radiotherapy 

(IMRT) but the treatment is still time consuming. The new rotation therapy 

paradigm, volumetric intensity modulated arc therapy (VMAT), may have the 

potential to reduce the treatment time while producing a comparable dose 

distribution. In this study we compare the dose distributions and the treatment 

times for conformal 3D radiotherapy (3D-RT), step and shoot IMRT and 

VMAT for planning target volumes (PTV) of anal cancer. 

Materials: CT datasets of 8 patients with anal cancer from our department 

formed the basis of this plan evaluation study. For comparison, a mean dose 

of 36 Gray (Gy) was chosen as prescription dose to the PTV that is initially 

treated for all patients (primary tumor, inguinal and pelvic lymph nodes) because 

it has the most complex geometry. The routinely applied refined 3D- 

Treatment Plan (Masterplan, Theranostic) was compared to a 9 beam step 

and shoot IMRT (Corvus 6.3, Nomos) and a VMAT plan with 2 rotations generated 

with ERGO++ 1.7 by Elekta based on a recently implemented modified 

Bortfeld-algorithm. All three treatment planning systems used the identical 

CT datasets and the same OAR (femoral neck, small intestine and bladder). 

To compare these three techniques, the dose volume histograms (DVH) of 

PTV and OAR’s as well as the total treatment time (TTT) were used. Additionally, 

the homogeneity index (HI) and the conformality index (CI) calculated 

as suggested by the RTOG guidelines were analysed. All data are presented 

as mean values ± standard deviation (SD). 

Results: VMAT provided the best PTV coverage as indicated by the following 

metrics (isodose as percentage of prescription dose (PD) encompassing 

95% of the PTV / percentage of tissue outside the PTV encompassed by 95% 

of PD). For 3D-RT the mean values were (94.7±0.7% / 5.4±1.5%), for IMRT 

(89.8±1% / 0.7±2.6%) and for VMAT (92±1% / 2.2±0.9%). The mean CI 

over all 8 patients was 1.71±0.11 for 3D-RT, for IMRT 1.33±0.21 and for 

VMAT 1.39±0.08. The mean homogeneity index (HI36) for the prescribed 

dose of 36 Gy was 1.15±0.02 for IMRT, 1.06±0.01 for 3D-RT and 1.11±0.02 

for VMAT. The doses of the OAR’s for 3D-RT and VMAT were comparable, except 

for the bladder (minimal dose Dmin [99.0% of PD] for 3D-RT 30±4.8Gy 

and VMAT 21±9.3 Gy). The time for the gantry movements and for beamon-time 

(BOT) were measured and stored as total treatment time (TTT). The 

TTT for 3D-RT (220 s) was much shorter than for IMRT (557 seconds). The 

estimated TTT of the VMAT technique is 180 seconds. 

Conclusions: The new VMAT technique provides excellent treatment planes 

with highest conformality and homogeneity. The short treatment delivery time 

together with low primary monitor units are the most important advantages.


1402 poster 

FEASIBILITY STUDY OF A 2D ION CHAMBER ARRAY AND THE 

MULTICUBE PHANTOM FOR QUALITY ASSURANCE OF RAPIDARC 

J. Bocanek 1 , I. Gomola 2 , T. Depuydt 3 , F. Van den Heuvel 3 

1 VARIAN MEDICAL SYSTEMS INTERNATIONAL AG, Zug, Switzerland 

2 IBA DOSIMETRY, Schwarzenbruck, Germany 

3 LEUVEN UNIVERSITY HOSPITALS, GASTHUISBERG, Radiotherapy, Leuven, 

Belgium 

Purpose: In this work we have evaluated suitability of a Helical 

Dosimetry R○system, consisting of a 2D ion chamber array (I’mRT MatriXX, 

IBA Dosimetry, Germany) and a dedicated phantom made from Plastic 

Water R○called MULTICube for dosimetry quality assurance of RapidArcTM 

volumetric modulated arc therapy. 

Materials: The angular dependence of the MatriXX response in the MUL- 

TICube phantom was studied in 6 and 18 MV x-ray beams produced by a 

Clinac 2100C/D (Varian). The MULTICube with MatriXX was irradiated with 

a 10x10 cm field size at 45 different gantry angles covering the range from 

0-180 ◦ . The phantom was rotated by 90 ◦ to avoid couch top attenuation influence 

in the measurements. The response of the MatriXX central pixel was 

compared with the response of a cylindrical ionization chamber (CC08, IBA 

Dosimetry, Germany) inserted into a MatriXX dummy. A dose calculation was 

performed on a CT scan of the MULTICube with MatriXX applying the Analytical 

Anisotropic Algorithm (AAA) and the Pencil Beam Convolution (PBC) 

calculation algorithms of the Varian Eclipse TPS at corresponding gantry angles. 

The MatriXX measurement was compared with the cylindrical chamber 

measurement and the calculated dose distribution in the active plane of the 

detector. In addition, MCNPX Mote Carlo simulations of the angular dependence 

of the ion chamber array have been performed. Additionally to the 

angular dependence study several Rapid Arc plans were delivered to the Helical 

Dosimetry system. Rapid Arc plans produced by the Eclipse planning 

system (Varian) have been delivered to the phantom several times to verify 

reproducibility of the delivery. 

Results: A good agreement was found between measurements performed 

with a cylindrical IC and the corresponding detector of the MatriXX. Without 

any specific adaptation of the phantom a correspondence between the AAA 

calculation algorithm and measurement was found of less than 2.2% except 

for the angles 88 ◦ to 92 ◦ where discrepancies up to 4.9% were observed (Fig 

1). The agreement between the Monte Carlo calculation and the response 

of 2D array was found within 1.5 % for 0 ◦ /180 ◦ angle ratios. All Rapid Arc 

measurements revealed good agreements between calculated and measured 

dose distributions. The evaluation of the results using gamma index with 3% 

/ 3 mm criteria revealed gamma values < 1 in at least 96% of the values of all 

plans. 

Conclusions: The use of the MatriXX with the MULTICube phantom was 

found as fast and reliable dosimetry method for QA of RapidArc treatment 

delivery. The dynamic readout capability of the MatriXX allowed us to analyze 

the accuracy of 2D dose distribution delivered by RapidArc for all arc 

segments in a time stamps bellow 100 msec. 

1403 poster 

HELICAL TOMOTHERAPY AND MLC-BASED IMRT IN TREATING 

BRAIN AND CRANIO-SPINAL TUMORS 

C. Shi 1 , P. Mavroidis 2 , C. Esquivel 1 , B. Costa Ferreira 3 , A. Diaz 1 , N. 







Purpose: Helical Tomotherapy (HT) and MLC-based IMRT are radiation 

modalities, which produce highly conformal dose distributions. Their clinical 

effectiveness is assessed here by using physical and biological criteria such 

as the biologically effective uniform dose (BEUD) and the complication-free 

tumour control probability (P+). 

Materials: HT and linac MLC-based step-and-shoot IMRT treatment plans 

were developed for two clinical cases of brain and cranio-spinal cancers. 

Specifically, a 57-year-old male with recurrent hemangiopericytoma of the 

brain was treated to 54 Gy in 30 fractions and a 15-year-old male with medulloblastoma 

was treated on the cranio-spinal axis to 40 Gy in 20 fractions. In 

the second case, the brain was treated with IMRT beams and spine treated 

with IMRT plus 3D conventional beams. Two beams of 6MV photon energy 

were set for brain-PTV. Six spine beams of 18MV photon energy were set for 

spine-PTV (three for upper spine and three for lower spine). By using BEUD 

as the common prescription point of the treatment plans and plotting the tissue 

response probabilities vs. BEUD for a range of prescription doses, the 

different dose distributions could be compared. 

Results: According to the radiobiological analysis, in the brain cancer case 

the HT and the MLC-based IMRT treatment plans give similar results (P+ of 

66.0% and 63.4% for a BEUDPTV of 63.0 Gy and 62.0 Gy, respectively). The 


total complication probabilities, PI are 13.4% and 13.1%. In both cases, the 

dose limiting tissue is the speech area. In the cranio-spinal cancer case, the 

HT and MLC-based IMRT radiation modalities give a P+ of 84.1% and 28.4% 

for a BEUDPTV of 50.6 Gy and 44.0 Gy, respectively. The respective PB 

values are 86.4% and 51.3%, whereas the PI values are 2.3% and 23.0%. 

The control probabilities of the Brain-PTV are 91.4% and 81.2%, whereas of 

the Spine-PTV they are 94.5% and 63.2%, respectively. The dose limiting 

tissues are the lung and left kidney. 

Conclusions: Although both HT and MLC based-IMRT can produce highly 

conformal dose distributions in certain complex clinical cases the HT radiation 

modality may show clearly better properties in producing more effective dose 

distributions. In such situations, the traditional dose based evaluation tools, 

which are used to guide the optimization algorithms can be complemented by 

P+ BEUD diagrams to compare and improve treatment plans.

1404 poster 


IMPLEMENTATION AND CLINICAL RESULTS OF CONE-BEAM 

CT-GUIDED CRANIAL STEREOTACTIC RADIOSURGERY USING 

VARIAN’S ON-BOARD IMAGER SYSTEM 

K. Seiersen 1 , L. Præstegaard 1 , U. V. Elstrøm 1 , J. Petersen 1 , P. R. 

Poulsen 1 , H. Schultz 2 , A. Traberg 1 , M. Høyer 2 

1 AARHUS UNIVERSITY HOSPITAL, Department of Oncology, Department of 

Medical Physics, Aarhus C, Denmark 


Denmark 

Purpose: Since May 2007, Aarhus University Hospital has performed 

frameless intra-cranial stereotactic radiosurgery (SRS) using cone-beam CT 

(CBCT) guided positioning of patients. In comparison to invasive frame-based 

SRS, CBCT-guided SRS has the benefit of good patient comfort, planning 

and treatment at separate days (similar to conventional radiotherapy), and 

the possibility of fractionated treatment. 

Materials: Patients are treated using the Varian On-Board Imager CBCTsystem. 

All individual geometrical errors for localizing a target with CBCTguidance 

have been carefully evaluated, and the accuracy of the complete 

clinical process has been tested for a cranial phantom with natural human 

bony anatomy.At the treatment session, the patient is immobilized in a conventional 

non-stereotactic head-and-neck mask system. After initial positioning 

using external landmarks, a CBCT-scan is acquired, providing automatic 

correction of the patient position. A second scan verifies the patient position, 

and a third CBCT-scan after the treatment provides information about 

the intra-fraction motion. The intra-fraction motion is also monitored during 

delivery of the individual fields using cine MV imaging. 

Results: All individual geometrical errors of CBCT-guided SRS are small, resulting 

in a total random target localization error of only 0.6 mm along all axes 

in case of negligible intra-fraction patient motion. The treatment error of a 

cranial phantom is in excellent agreement with the sum of the individual geometrical 

errors.As of March 2008, eight patients with cranial metastases have 

been treated using this technique. The treatment time varied between 40 and 

75 minutes for positioning, CBCT-scans, and treatment of one isocenter. Average 

treatment time was 55 minutes. Seven patients received treatment to 

one isocenter, and one patient received treatment to two isocenters. Further, 

one patient received a fractionated treatment of 27 Gy in 3 fractions. The 

intra-fraction patient motion during treatment is below 1 mm along any axes 

for most patients. 

Conclusions: High-precision cranial SRS using CBCT-positioning is shown 

to be feasible, efficient, and comfortable for the patient. The accuracy is comparable 

to invasive frame-based SRS, and fractionated SRS is possible. With 

more experience, faster software, and a new fixation with better clearance, 

the average treatment time is expected to decrease to 35-40 minutes. 

1405 poster 

IMPROVEMENTS IN THE AAA DOSE CALCULATION ALGORITHM 

FOR RAPIDARC TM TREATMENTS: MLC AND COUCH MODELLING 

A. Van Esch 1 , D. Huyskens 1 , S. Siljamäki 2 , M. Rusanen 2 , J. Kauppinen 

2 , L. Tillikainen 2 , H. Riem 3 

1 

7SIGMA, Tildonk, Belgium 

2 

VARIAN MEDICAL SYSTEMS FINLAND, Department of Research and 

Development, Helsinki, Finland 

3 

VARIAN MEDICAL SYSTEMS INTERNATIONAL AG, Department of Image 

Processing and Research, Zug, Switzerland 

Purpose: For the delivery of RapidArcTM treatments (a form of volumetric 

arc therapy, Varian Medical Systems), a new optimisation algorithm and a 

new version of the MLC controller was developed, permitting variable dose 

rate treatments. For these complex treatments, some refinements were made 

to the AAA dose calculation, now including the tongue & groove effect as well 

as the presence of the treatment couch. The purpose of this study was to 

evaluate the accuracy of these modifications for RapidArc treatments using 

test plans and patient plans. 

Materials: Rapidarc measurements were performed on a Clinac iX with film 

and with the Seven 29 2D ion chamber array in the Octavius phantom. RapidArc 

dose calculations were performed with a non-clinical research version of 

Eclipse. A series of tests plans were created to evaluate the different MLC parameters 

now modelled (transmission, dosimetric leaf separation and tongue 

& groove effect). The impact of the treatment couch was firstly quantified by 

means of static open field deliveries. Phantom measurements of the same 

RapidArc treatments on different couch tops allowed an intercomparison of 

the available couch tops with respect to their impact on the clinical dose deliveries. 

Results: When including the tongue&groove effect as an additional parameter 

in the dose calculation for dynamic arc treatments, the agreement between 

measurement and calculation was found to be within 2%, 2mm within the volume 

of interest, for treatment deliveries avoiding beam incidences through 

the treatment couch. In order to maintain this dosimetric accuracy, modelling 

of the treatment couch in the TPS was found to be mandatory. 

Conclusions: An overall agreement of 3%, 3mm between dose calculation 

S 447 

and phantom measurements can be obtained for RapidArc treatment deliveries 

when including the tongue & groove effect and the presence of the treatment 

couch into the dose calculation. 

1406 poster 

INTENSITY-MODULATED RADIOTHERAPY (IMRT) WITH COMPEN- 

SATING FILTERS: BRAZILIAN EARLY EXPERIENCE AND QUALITY 

ASSURANCE (QA) RESULTS 

M. Setti 1 , I. Horst 1 , A. P. Galerani 2 , C. Neto 2 , A. Bouza 3 , N. Karpienski 

4 , J. C. Pereira 2 

1 CLINIRAD, Physics, Curitiba, Brazil 

2 CLINIRAD, Radiotherapy, Curitiba, Brazil 

3 MEVIS, São Paulo, Brazil 

4 MAC GAYVERS, Curitiba, Brazil 

Purpose: IMRT can be delivered with compensating filters build individually 

for each field after precise coordinates are generated from a treatment planning 

system (TPS) to create a costumed block. Quality assurance (QA) is 

crucial in this technique. This study validates our initial experience with IMRT 

using compensating filters and ascertains QA issues for this modality. 

Materials: TPS used in this setting was CAT3D (Mevis, Brazil). System commissioning 

with plane parallel ion chamber in build up was validated using 

several readings for different widths of lead blocks (2, 5, 10, 18, 27, 38, 48, 

and 58 mm) and for different field sizes (3, 8, 12, 15, and 20 mm). Doses 

outside of the central axis (10, 20, 30, 50, and 80 mm) were also referenced. 

Measurements were obtained using energy of 6 MV and the attenuation coefficient 

model was acquired for pencil beams. Between January and March of 

2008, 5 patients with prostate cancer were planned to a total dose of 78 Gy to 

95% (D95) of the planned treatment volume (PTV) with 2 Gy /day fraction. A 

five-field arrangement was used After the planning treatment was approved, 

points for the block confection were generated and arranged with a refined 

resolution digital computer numerical control (CNC) machine. MapCHECK 

absolute dose was used as part of the QA program. An acceptance criterion 

was 90% of gamma value with a 3% dose variation in 3 mm. Dose-volume 

histograms (DVH) were generated and analyzed for target and organs at risk 

(OARs). Maximum accepted punctual dose to the right/ left femur head was 

56Gy. Constraints for rectum and bladder volume of 15% (D15), 25% (D25), 

35% (D35), and 50% (D50) were, respectively, 75 Gy, 70 Gy, 65 Gy, 60 Gy 

and 80 Gy, 75 Gy, 70 Gy, and 65 Gy. The ratio between the planning dose 

and constraint dose was used as quality coefficient (QC) and should be < 

1. In vivo dosimetry with diodes was also assessed for QA intentions in all 

treatment fractions. 

Results: The maximum modulation acquired was 92%. Mean D95 was 77.6 

Gy with standard deviation (SD) of 1.4 Gy. Each field had approximately 100 

MU. Mean planned D15, D25, D35, and D50, were, in Gy, 72.7 (SD=0.7), 66.7 

(SD=2.5), 62.3 (SD=2.1), and 54.6 (SD=2.1), respectively for rectum and 79.3 

(SD=0.9), 74.3 (SD=1.9), 66.7 (SD=3.5), and 54.6 (SD=8.5) respectively for 

bladder. Right/ left femur had a mean maximum dose of 54.5 Gy (SD=1.7). 

Mean value from MapCHECK was 97.9% with (SD= 0.5%). Mean QC was 

0.954 (SD =0.03). In vivo results demonstrated mean variation of 2.8% (SD= 

1.7%). 

Conclusions: Delivery of IMRT with compensating filters is feasible and reliable. 

Quality assurance methods should be carefully implemented. Doses 

applied to target and OARs were considered clinically acceptable for treatment. 

Cost-effective fabrication makes it an attractive modality. 

1407 poster 

INTRACRANIAL STEREOTACTIC RADIOTHERAPY USING A VARIAN 

TRILOGY AND THE CMS XIO TPS 

M. Essers 1 , S. Hol 2 , M. van Wieren 1 , P. van der Tol 1 , D. Eekers 2 , M. van 

de Pol 2 

1 

DR. BERNARD VERBEETEN INSTITUTE, Medical Physics, Tilburg, 

Netherlands 

2 

DR. BERNARD VERBEETEN INSTITUTE, Radiotherapy, Tilburg, Netherlands 

Purpose: Since 2002, stereotactic radiosurgery is performed in our institute 

using a Gamma Knife system (Elekta). The purpose of the present study was 

to develop a complementary intracranial stereotactic radiotherapy program for 

fractionated treatments, using a linear accelerator in combination with a nondedicated 

TPS, which is mainly intended for standard treatments. First, the 

accuracy of the dose calculations for small fields was established. Second, 

an optimal treatment plan was developed. 

Materials: The CMS XiO TPS was developed for conventional and IMRT 

treatments using field sizes of at least 3x3 cm 2 . During modelling of a 6 

MV Varian Trilogy machine with the MLC-120 (5 mm leaf width), special attention 

was paid to field sizes smaller than 3x3 cm 2 . Input as well as QA 

measurements were performed using small ionization chambers, diodes and 

GafChromic films. The accuracy of dose calculations was determined for single 

fields and total treatment plans using a head phantom for field sizes from 

1x1 to 4x4 cm 2 . To develop an optimal standard treatment plan, several treatment 

plan techniques were compared for 5 patients with different positions


and sizes of the tumor: arcs with fixed MLC field sizes, "arcs" with 3 to 7 

static beams for each of 5 arcs conformed to the PTV, and "arcs" with 3 to 

7 static IMRT beams. DVHs of the PTV, the whole brain and organs at risk, 

as well as parameters such as the conformity index to determine the lesion 

coverage, dose homogeneity, and dose fall-off were compared. 

Results: It turned out that using one beam model for all field sizes ranging 

from 1x1 to 40x40 cm 2 is sufficient. For field sizes smaller than 4x4 cm 2 , photon 

diode measurements were used as input. Film dosimetry showed that the 

actual 20-80% penumbra is slightly smaller (2.6 mm) than calculated with the 

TPS (4.3 mm). For field sizes of 1x1 cm 2 , uncertainties in dose calculations 

up to 10% were found. However, for field sizes of 1.5x1.5 cm 2 and larger, the 

dose calculations are accurate within 2% or 1.5 mm, if a calculation grid size 

of 2 mm is applied. It turned out that a rather simple IMRT technique, with 

only 2 or 3 segments per field for 15 non-coplanar standard beam directions, 

resulted in an optimal dose distribution. The target conformity index using this 

technique ranged between 1.3 and 1.7, while it ranged from 2.3 to 3.2 for the 

fixed arcs technique, which overall showed the worst results for all patients. 

The IMRT technique also resulted in the smallest volume receiving 50% of 

the prescribed dose, the smallest dose heterogeneity, and the lowest dose to 

organs at risk. 

Conclusions: Accurate intracranial stereotactic radiotherapy using field sizes 

as small as 1.5x1.5 cm 2 can be delivered using equipment already available 

for non-stereotactic treatments. 

1408 poster 

INVERSE-PLANNED RESPIRATORY-GATED INTENSITY MODU- 

LATED RADIOTHERAPY FOR TREATMENT OF HIGH-RISK BREAST 

CANCER PATIENTS 

D. Purina 1 , O. Utehina 2 , S. Popov 1 , I. Slosberga 3 , I. Vevere 2 , D. Emzins 

2 , J. Berzins 4 

1 LATVIAN ONCOLOGY CENTER OF RIGA EASTERN CLINICAL UNIVERSITY 

HOSPITAL, Medical Physics, Riga, Latvia 


HOSPITAL, Radiotherapy, Riga, Latvia 


HOSPITAL, Diagnostic Radiology, Riga, Latvia 


HOSPITAL, Science, Riga, Latvia 

Purpose: Intensity Modulated Radiotherapy (IMRT) becomes standard treatment 

for Head and Neck and prostate cancers. However, wide clinical use 

of IMRT for other cancer localizations is still under investigation. One of the 

most controversial localizations from the IMRT usage point of view is breast 

cancer. In this study inverse-planned, multiple fields Respiratory-Gated (RG) 

IMRT plans for two high-risk breast cancer patients were compared to the 

three-dimensional conformal radiotherapy (3D-CRT) plans for the same patients. 

Aim of this study was to show that IMRT, if carefully justified, is beneficial 

for some high-risk breast cancer patients, 

Materials: Two patients with high-risk breast cancer received IMRT courses 

in 2007 in Latvian Oncology Center. It was necessary to irradiate in addition to 

whole breast supra- and infra-clavicular lymph nodes and internal mammary 

lymph nodes. For one patient all levels of axilary lymph nodes were included 

in target volume as well. One patient had primary cancer in the right breast 

and one in the left breast. 3D-CRT plans, created for both patients, leaded 

to non-optimal dose distributions, and due to this inverse-planned, multiple 

fields RG IMRT plans were created. Multiple parameters were used for plan 

evaluation, including: maximal doses in target volumes and normal tissues, 

minimal dose to target volumes, mean lung dose, mean and maximal heart 

dose, Normal Tissue Complication Probability (NTCP) for lung pneumonitis 

and heart injury, maximal and mean dose in the contralateral breast. 

Results: For both patients IMRT plans leaded to much more conformal dose 

distributions in comparison with 3D-CRT ones. Significant reduction of the 

maximal dose to target volumes and normal tissues was achieved in the 

IMRT plans. At the same time, minimal dose to target volumes was significantly 

higher in comparison with 3D-CRT plans. However, IMRT plans 

leaded to much larger low dose volume in both lungs, and so higher probability 

of radiation-induced carcinogenesis in lungs for the IMRT technique. Maximal 

dose to the contralateral breast was significantly lower for IMRT plans. 

However, mean dose in contralateral breast was significantly higher for IMRT 

plans, so leading to higher probability of radiation-induced carcinogenesis. 

All dose distribution parameters for the heart were significantly better for the 

IMRT plans. Using IMRT significant reduction of NTCP for heart and lungs 

was achieved. 

Conclusions: Multiple fields, inverse planned RG IMRT can be justified for 

some high-risk breast cancer cases, where it is needed to irradiate all nodal 

volumes along with the whole breast, taking into account unacceptably high 

risk of normal tissue damage in 3D-CRT plans. However, use of the IMRT 

for breast treatments should be carefully justified for each high-risk breast 

cancer patient individually as it will unavoidably lead to higher risk of radiationinduced 

carcinogenesis in contralateral breast and lungs. 

1409 poster 

IRRADIATION OF PARANASAL SINUS TUMORS: COMPARISON OF 

CONFORMAL THREE-DIMENSIONAL VERSUS CONVENTIONAL 


S. Kamian 1 , A. Kazemian 2 , M. Aghili 2 , M. Esfahani 2 , E. Mohammadi 2 

1 ATOMIC ENERGY ORGANIZATION OF IRAN, Department of Radiation 

protection, Tehram, Iran Islamic Republic of 

2 CANCER INSTITUTE, Radiation Oncology, Tehran, Iran Islamic Republic of 

Purpose: To assess the possibility of delivering a homogeneous irradiation 

with respect to maximal tolerated dose to the optic pathway for paranasal 

sinus tumors. 

Materials: Treatment planning with conformal three-dimensional (3D) and 

conventional two dimensional (2D) was done on the CT scans of the twenty 

patients who had early or advanced paranasal tumors. None of the cases 

were previously irradiated. Two to four individually shaped isocentric noncoplanar 

field arrangement were designed. Dose-volume histograms (DVH) 

for the planning target volume (PTV) and the visual pathway including globes, 

chiasma and optic nerves were compared in two treatment plannings. 

Results: The area under curve (AUC) in the DVH of the globes in the same 

side and contralateral side of tumor involvement was significantly higher in 

2D planning (P0.05). 

The AUC in the DVH of PTV was not significant (201.1±16.23 mm in 2D 

planning and 201.15±15.09 mm3 in 3D planning). The volume of PTV which 

received 90% of the prescribed dose was 96.9±4.41 cc in 2D planning and 

97.2±2.61 cc in 3D planning (P>0.05). 

Conclusions: Three dimensional conformal radiotherapy for paranasal sinus 

tumors enables the delivery of radiation to tumor with respect to critical organs 

with a lower toxicity to optic pathway. 

1410 poster 

IS 3-D PLANNING SUPERIOR TO CONVENTIONAL PLANNING IN 

WHOLE BRAIN IRRADIATION? 

Y. Bolukbasi 1 , A. Toy Inal 2 , E. Gez 3 , R. Bar-Deroma 3 , A. Kuten 3 , Y. 

Anacak 1 

1 EGE UNIVERSITY HOSPITAL, Radiation Oncology, Izmir, Turkey 

2 AKDENIZ UNIVERSITY HOSPITAL, Radiation Oncology, Antalya, Turkey 

3 RAMBAM MEDICAL CENTER, Oncology, Haifa, Israel 

Purpose: To evaluate the superiority of using CT simulation and 3D planning 

over conventional simulation in the treatment planning of whole brain irradiation. 

Materials: Cranial CT scans of 33 patients from Ege University Hospital and 

Rambam Medical Center were used in this study. Targets (brain and cribriform 

plate) and organs at risk-OARs (hypophysis, eyeballs and lenses) were 

contoured by one of the authors (DR-1). Digitally reconstructed radiographs 

(DRRs) were produced where the contours of targets and OARs were visible 

(switched-on) and DR-1 draw the german helmet fields on these DRRs. Care 

was taken to cover all brain, cribriform plates and retro-orbital space; and to 

exclude lenses and eyeballs as much as possible. No spesific procedure was 

used to spare hypophysis. Then contours of targets and OARs were made 

incisible (switched-off) and DRRs without any markings of any structure were 

produced. These were similar to those lateral cranial radiographs obtained 

in conventional simulation. Other two authors DR-1 and DR-2 draw separately 

german helmet fields on these DRRs as routinely done in conventional 

simulation planning. All three authors were unaware of the contours of each 

others. Mibrain dose was normalized to 100% and % doses to targets and 

OARs were calculated. The results with both methods were compared. 

Results:


Conclusions: Dose to the target structures (brain and cribriform plates) was 

not different in two techniques. Regarding the OARs the lens doses were 

lower when 3D technique was used, but the dose to eyeballs and hypophysis 

was similar. We conclude that in planning whole brain irradiation the use of 

CT and 3D technique has no superiority of target coverage over conventional 

simulation. Better sparing of the lenses may be advantageous. 

1411 poster 

MODIFICATION OF ELECTRON APPLICATORS OF THE LINEAR 

ACCELERATOR FOR ISOCENTRIC TREATMENTS 

M. Tenhunen 1 , H. Nyman 1 , S. Strengell 1 , L. Vaalavirta 1 

1 HELSINKI UNIVERSITY CENTRAL HOSPITAL, Department of Oncology, 

Helsinki, Finland 

Purpose: Isocentric treatment technique is a standard method for photon 

radiotherapy with the primary advantage of requiring only a single patient 

set-up procedure for multiple fields. However, in electron treatments the size 

of standard applicators does not generally allow to use isocentric treatment 

technique. In this study we have modified and dosimetrically tested electron 

applicators for isocentric treatments in combination with photons with a special 

emphasis on postmastectomy radiation therapy. 

Materials: Standard electron applicators of the Varian Clinac 2100CD linear 

accelerator were shortened by 10 cm allowing of ca. 90 cm < SSD < 95 cm in 

electron fields. Shortened applicators were commissioned and configured for 

the electron calculation algorithm of the treatment planning system (Varian 

Eclipse: Gaussian Pencil Beam). The field arrangement of postmastectomy 

radiation therapy was modified aiming at improving the dose homogeneity in 

the electron-photon field gap region. 

Results: Depth dose characteristics of the shortened applicators remained 

practically unchanged from standard applicators. Penumbrae were broadened 

by 1-3 mm depending on the electron energy and depth as the air gap 

was increased from 5 cm of the standard applicator (SSD=100 cm) to 10 cm 

of the shortened applicator (SSD=95 cm); this could be modelled adequately 

in the TPS. Isocentric treatment technique allowed to increase a number of 

fields within the same time slot for the treatment delivery as with our standard 

technique. Using three photon fields with different gaps and overlaps 

between the electron and photon field segments the inhomogeneity of the 

dose distribution within the gap region could be reduced from 70-130 % to 

ca. 85-115 %. So far the short applicators have been used clinically for >50 

patients receiving postmastectomy radiation therapy with acceptable results 

considering acute toxicity of the treatment. 

Conclusions: It is possible to apply an isocentric treatment technique in postmastectomy 

radiation therapy with electron and photons. The homogeneity 

of the dose distribution can be improved by adding a number of fields with no 

extra time for the treatment delivery. 

1412 poster 

OPTIMAL TECHNIQUE FOR DOSE-ESCALATED RADIOTHERAPY 

TO THE PROSTATE GLAND IN PATIENTS WITH BILATERAL HIP 

PROSTHESES 

V. Kong 1 , T. Rosewall 1 , C. Catton 1 , P. Chung 1 , C. Ménard 1 , P. Warde 1 , 

D. Vesprini 1 , A. Bayley 1 

1 PRINCESS MARGARET HOSPITAL, Radiation Medicine Program, Toronto, 

Canada 

Purpose: The presence of bilateral hip prostheses (BHP) in patients with 

prostate cancer poses significant challenges to the radiotherapy planning 

process due to the limited beam entry points that can be used to avoid the 

prosthetic implants. This study compares 3 different radiotherapy planning 

techniques in this group of patients. 

Materials: The planning CTs of 8 treated patients with BHP were used to 

compare step & shoot IMRT to 3f-CRT (anterior and 2 post-obliques) and 

S 449 

4f-CRT plans (2 anterior and 2 posterior obliques). CTV was the prostate 

alone, defined using CT/MR co-registration. PTV was created by a 10mm 

expansion on the CTV for all plans. The rectal wall (RW) was delineated from 

the anal verge to the rectosigmoid junction and the bladder wall (BW) was 

contoured from neck to the dome. Gantry angles were individualised for each 

patient to avoid beam entry through the prosthetic structures. Total dose of 

78Gy in 39 fractions was prescribed to minimum dose to CTV (IMRT plans) 

or to the center of the prostate gland (CRT plans). All plans were designed 

to achieve a PTV D99 > 95% and standard institutional dose constraints for 

BW/RW. Dose/volume parameters and conformity index (CI) were used for 

plan evaluation and comparison. Host factors that could influence the efficacy 

of the treatment plans were also explored. 

Results: Descriptive statistics of the plan dosimetry are summarized in Table 

1. On average, IMRT reduced the RW D50 and D30 by 25% and 12%, and 

the BW D50 and D30 by 31% and 19% compared to the CRT plans (p


1414 poster 

RADIATION SURVEY AROUND A LIAC MOBILE ELECTRON LINEAR 

ACCELERATOR FOR IORT 

M. Ciocca 1 , G. Pedroli 1 , R. Orecchia 2 , A. Guido 2 , F. Cattani 1 , R. 

Cambria 1 , U. Veronesi 3 

1 EUROPEAN INSTITUTE OF ONCOLOGY, Medical Physics, Milan, Italy 

2 EUROPEAN INSTITUTE OF ONCOLOGY, Radiation Oncology, Milan, Italy 

3 EUROPEAN INSTITUTE OF ONCOLOGY, Scientific Director, Milan, Italy 

Purpose: To perform a detailed analysis of the x-ray exposure rates and 

shielding assessment on a Liac mobile linear accelerator working in a conventional 

operating room (OR) for IORT. 

Materials: The Liac installed at our Institute delivers electron beams at nominal 

energies of 4-6-8-10 MeV. Radiation survey to determine photon leakage 

and scatter consisted of exposure measurements on a sphere of 1.5 m radius, 

centered on the titanium exit window of the accelerating structure, close to the 

thin scattering foil. Measurements were taken using a 30 cc calibrated cylindrical 

ion chamber in three orthogonal planes every 22.5 ◦ , with the maximum 

electron energy (10 MeV) and applicator size used in the clinical practice (10 

cm diameter). For each point, the Monitor Units corresponding to 10 Gy dose 

at the standard treatment distance and depth of maximum dose were delivered. 

Moreover, in a few selected points the quality of combined leakage and 

scatter radiation was determined, by using lead sheets surrounding the ion 

chamber, and additional measurements were performed for all electron energies. 

The contribution on photon scatter due to the utilization of metallic 

internal shielding in IORT was also evaluated. 

Results: In the two vertical planes, measured air kerma values ranged from 

approximately 6 (upper and rear sides of Liac) to 300 microGy (floor direction, 

just laterally to beam stopper), while in the horizontal plane values lower 

than 18 microGy were always found. Below the horizontal beam stopper, 52 

microGy were measured. A significant decrease of the exposure values as a 

function of beam energy was found only for the lowest one (4 MeV). Concerning 

the radiation quality, the transmission below 1 cm lead shield was about 

42% for all energies. The use of metallic internal shielding did not show to 

significantly increase photon scatter. Overall measurement uncertainty was 

estimated around 5% (1 SD), the highest contribution to it being represented 

by the ion chamber positioning. 

Conclusions: This study confirmed that Liac can safely work in an existing 

OR, while the need of movable added shielding mainly depends on patient 

workload. The exposure rates reported in the present investigation can be 

useful for those Centers planning to implement an IORT program using a 

mobile linear accelerator, to estimate in advance shielding requirements and 

admitted workload. 

1415 poster 

RADIOSURGERY WITH TOMOTHERAPY: RADIONICS INTERFIX 

S. Jaywant 1 , P. Hoban 2 

1 CANCER INSTITUTE OF NEW JERSEY/ROBERT WOOD JOHNSON UNIVER- 

SITY HOSPITAL, Radiation Oncology, New Brunswick, USA 

2 TOMOTHERAPY INC, Madison, USA 

Purpose: Helical Tomotherapy combines linear accelerator and computerized 

tomography (CT) technology to deliver intensity modulated radiation therapy. 

Whereas radiosurgical applications on a linear accelerator are now routine, 

these are currently at a developmental phase on Tomotherapy. The 

Radionics’ XknifeRT system together with its frames is well known for linac 

based stereotactic radiosurgery/radiotherapy. They have now developed the 

"InterFix" patient fixation kit for cranial applications with Tomotherapy. Initial 

results of the use of InterFix with Tomotherapy using a Rando head phantom 


Materials: The Radionics’ InterFix consists of a carbon fibre base board with 

an adapter that allows for attaching the CRW, GTC or the pediatric TLC 

stereotactic head frame. There are two separate boards, one for flat CT 

scanner tabletops and another for the Tomotherapy couch/tabletop. Thus 

identical cranial fixation is achieved during CT scanning, and, treatment with 

Tomotherapy. For the preliminary study of the system, a Rando head phantom 

was attached to the GTC frame. The GTC frame was then clamped onto 

the adapter for CT scanning. The CT localizer with nine rods was then placed 

onto the GTC frame. The three markers (as required for Tomotherapy) were 

placed at the top end of the CT localizer and not on the phantom/head. CT 

scan was acquired and transferred to the Tomotherapy planning station. A 

fictitious target and three critical structures were contoured and a treatment 

plan obtained. This plan was transferred to the Tomotherapy treatment machine. 

The GTC frame (with the phantom and the CT localizer) was clamped 

in the adapter of the InterFix board for use with the treatment machine couch. 

A pre-treatment MVCT scan was obtained and registration with the original 

KVCT planning scan was accomplished. 

Results: The registration results indicated that the CT localizer rods were 

matched and so was the anatomy within the phantom. The values for Pitch, 

Roll and Yaw were all zero. The shifts as per the registration were: Lateral 1 

mm; Longitudinal 2 mm and Vertical 3 mm. 

Conclusions: The GTC frame together with the CT localizer provides excellent 

immobilization. The three markers can be etched directly onto the CT 

Localizer. The shifts can be considered minimal since the phantom was not 

rigid in the frame; a patient would normally have a bite-block. Depth Helmet 

is now being incorporated into the system that will allow a verification even 

before the MVCT. 

1416 poster 

SMEARING OF HOT AND COLD SPOTS IN CONPAS TECHNIQUE 

BY RELOCATING THE ISOCENTER 

A. Strojnik 1 

1 INSTITUTE OF ONCOLOGY LJUBLJANA, Radiophysics, Ljubljana, Slovenia 

Purpose: In most bilateral head and neck tumors the target volume is shaped 

concavely around the spinal cord. With the prescribed target dose of up to 

70 Gy, the dose to the spinal cord has to be kept below 50 Gy. A complex 

3D CRT technique ConPas resolves this challenge but generates significant 

dose inhomogeneity within the target volume: 90% isodose cold spots and 

115% isodose hot spots of around 1 cm 2 are common. Since the estimated 

variation in daily patient set-up (3 mm) is not enough to reduce the dose 

extremes, additional intentional moving of the isocenter is proposed. 

Materials: 3D CRT treatments with ConPas technique were planned for several 

patients with either pharyngeal or laryngeal tumors. Although additional 

fIMRT fields were introduced to even out the inhomogeneities, hot and cold 

spot residues remained present. To simulate planned interfractional patient 

displacements, several points within 1 cm radius from the isocenter in the 

transverse plane were chosen to represent new isocenters, and an exact 

copy of the original plan (preserving beam MUs) was moved to each of them. 

Beams in the original plan were set wide enough to cover the entire PTV even 

after the relocation. This only negligibly increased the irradiated volume since 

most of the broadening extended outside of the patient. The combined multiisocentric 

plan was compared to the original, focusing on target volume dose 

coverage and maximum dose to the spinal cord. 

Results: Moving the isocenter broadened the strips of dose gradient close 

to the PTV boundaries. This resulted in slightly poorer dose coverage of the 

PTV. It also diminished the prominence of dose minima and maxima within the 

PTV which gave rise to improved homogeneity through most of the CTV. The 

maximum dose to the spinal cord did not increase if the distance between the 

PTV and the spinal cord was sufficient to minimize the influence of gradient 

broadening. 

Conclusions: The above method appears to yield profit in treatments where 

the spinal cord is well isolated from the PTV. The improvement of dose homogeneity 

allows a reduction of the number of fIMRT fields. The day-to-day 

displacing of the isocenter also decreases the effect of possibly inaccurate 

collimator jaw alignment which is crucial for the ConPas technique. 

1417 poster 

TREATMENT-PLANNING STUDY OF PROSTATE CANCER 

INTENSITY-MODULATED RADIOTHERAPY WITH AN ELEKTA 

LINEAR ACCELERATOR WITHOUT A FLATTENING FILTER 

P. Kelly 1 , S. Buckney 2 , S. af Wetterstedt 2 , J. Armstrong 1 , P. McCavana 2 , 

B. McClean 2 

1 ST LUKES HOSPITAL, Radiation Oncology, Dublin, Ireland Republic of 

2 ST LUKES HOSPITAL, Physics, Dublin, Ireland Republic of


Purpose: To assess the feasibility of IMRT for prostate cancer using flattening 

filter-free photon beams and to determine the dosimetric characteristics of 

flattening filter-free beams in this setting. 

Materials: Generate clinically acceptable IMRT plans for 10 patients with 

localised prostate cancer. For each patient 2 plans were generated using 

6MV photons, one with and one without the flattening filter. The prescription 

dose was 74 Gy to the 100% isodose. Identical numbers of beams, beam 

orientations, dose-volume constraints and cost functions were applied to all 

plans. Treatment was delivered using a 5-field step-and-shoot technique. 

Plans were generated with Oncentra MasterPlan (Nucletron) version 3.0 using 

a pencil beam algorithm applying inhomogeneity correction.Dosimetric 

differences were determined from dose-volume histograms for organs at risk: 

rectum, bladder and femoral heads. Monitor unit requirements with and without 

the flattening filter were recorded. Conformity index and minimum and 

maximum PTV doses were compared. Two-tailed paired t tests were used to 

evaluate the significance of observed differences. 

Results: Plans with unflattened beams required significantly fewer monitor 

units per plan. PTV coverage was less uniform with unflattened beams. Organ 

at risk doses were similar with flattened and unflattened beams. 

Conclusions: At 6 MV clinically acceptable IMRT plans can be generated 

with unflattened beams. Dosimetrically, flattening filter-free plans were similar, 

although PTV coverage was less uniform. Plans with unflattened beams 

required significantly fewer monitor units, thereby reducing treatment delivery 

times and reducing dose outside of the intended treatment volume, potentially 

reducing the risk of second malignancy. Further clinical IMRT studies utilising 

unflattened beams is warranted. 

1418 poster 

USE OF CUSTOM-SHAPED COMPENSATORS FOR MODULATED 

ELECTRON RADIOTHERAPY TREATMENTS 

P. Tynan 1 , S. Stathakis 2 , N. Papanikolaou 2 



Purpose: To demonstrate modulation of electron beams using compensators 

in order to create conformal treatments for modulated electron radiotherapy 

(MERT) 

Materials: Using a plastic water phantom, a simulated treatment with a custom 

compensator was designed for a simulated superficial tumor. The plan 

was created using forward planning for delivery with acrylic compensators 

of various thicknesses and beams of different energies and field sizes. After 

placing the appropriate compensator in a 10 x 10 cm2 electron applicator, 

treatments consisting of multiple energies were delivered by a Varian 

Clinac 23EX linear accelerator. Sheets of Kodak EDR2 radiographic film were 

placed vertically along the central axis and horizontally at the depth of maximum 

dose within the phantom. Films were developed then scanned with a Vidar 

DosimetryPro scanner, and dosimetric data was extracted with RIT 113v5 

dosimetry software. Isodose lines from the films were then compared to a 

simulated tumor to determine whether compensator-based delivery showed 

potential for clinical use. A sample plan and target volume, shown in the figure, 

illustrate a field achieved using a two-layer acrylic compensator and a 

combination of 9 and 16 MeV electrons. The 50%, 70%, 90%, and 100% 

isodose lines (IDL) are shown, with the tumor volume falling within the 100% 

IDL. 

Results: By delivering treatments consisting of a combination of electron energies, 

shaping of complex fields was achieved. These fields yielded dose 

distributions that would be clinically suitable for use when treating irregular 

tumors. It was noted that on some plans the skin dose was a large enough 

fraction of the maximum dose that it may prove to be a limiting factor. A combination 

of multiple energies per beam portal might be a solution in order to 

overcome the high surface dose problem. Also, compensator material selection 

needs to be investigated in order to use materials with the most favorable 

characteristics for MERT. 

Conclusions: It is possible to use simple, inexpensive compensators to deliver 

clinically useful beams for MERT. Problems associated with the use of 

compensators like high surface dose need to be further investigated. 

1419 poster 

S 451 

VERIFICATION OF A GATING SYSTEM FOR STEREOTACTIC 

RADIATION TREATMENT 

S. Koch 1 , R. Bolt 1 , H. Meertens 1 , H. Langendijk 1 , A. van ’t Veld 1 

1 UNIVERSITY MEDICAL CENTER GRONINGEN, Department of Radiation 


Purpose: Respiratory gating is a prerequisite for precise (stereotactic) irradiation 

of moving targets such as liver tumors. Aim of this study was to verify a 

gating system designed for this purpose. A commercially available phantom 

was used to simulate respiratory motion of liver tumors and to assess the 

accuracy of dose delivery with gated fields. 

Materials: The Adaptive Gating module from BrainLAB AG allows to trigger 

the treatment beam of the Novalis linac each time the target passes through 

the isocenter. Target position at a specific phase of the breathing cycle is derived 

from stereoscopic X-ray images. A BrainLAB ExacTrac Gating Phantom 

simulated both external and internal breathing motion effects in liver treatments. 

Body markers were attached to the vertically moving part in order to 

record a breathing signal. In these tests, the motion amplitude in horizontal 

(G-T) direction was approx. 2 cm at a rate of 12-15 min-1. A 20% beam-on 

interval was specified around the equilibrium position. The phantom features 

an embedded spherical marker (5 mm) representing a target volume. We 

performed a gated single field Winston-Lutz test with the center of the marker 

defined as treatment isocenter. A radiochromic film was placed on the stationary 

platform of the phantom. During exposure, the radio-opaque marker 

creates a shadow on the film. The position of the shadow relative to the field 

boundaries reflects the targeting accuracy. Dose distributions were compared 

with gating either at the exhale phase only, or both at the exhale and inhale 

phase. In the second case the dose distribution can be more blurred due 

to time delays in the linac hardware. This was verified by means of a radiochromic 

film placed on top of the moving phantom. Finally, dosimetric 

consistency was examined using an ionization chamber. A reference reading 

was obtained by irradiating the motionless phantom with a 100 cm2 field. 

Then the same number of monitor units was applied to the phantom in motion. 

We also compared dose in gated vs. static conditions for smaller field 

sizes down to 6 mm. 

Results: The gated Winston-Lutz test demonstrated high targeting accuracy 

in gated mode. The shadow of the marker was displaced less than 1 mm from 

the field center (acceptance value: 2 mm). The second test confirmed that 

the system correctly compensates for hardware latencies: additional dose 

blurring with beam on during exhale + inhale was less than 1.5 mm. Furthermore, 

there was no measurable difference in absolute dose for static and 

gated operation. Only when the field size was reduced to 6 mm, a lower dose 

was measured in gated mode. However, such small fields are not used for 

extracranial treatments. 

Conclusions: The BrainLAB Adaptive Gating module well satisfied the acceptance 

criteria for dose delivery to a moving target. This new technique has 

thus become available at our department for stereotactic treatment of patients 

with liver metastases. 

1420 poster 

VIDEOCOACHING AS BIOFEEDBACK TOOL TO IMPROVE GATED 

RADIOTHERAPY OF BREAST CANCER: EXPERIENCES AFTER 2 

YEARS OF CLINICAL USE 

P. Cossmann 1 , A. Stuessi 1 , U. Gneveckow 1 , C. von Briel 1 


Switzerland 

Purpose: Gated treatments using the Varian RPM-gating system include in a 

standard configuration a coaching tool based on voice commands ("breathe-


in"/"breathe-out") called audio-coaching. As this configuration does not include 

feedback information like amplitude and breathing period, there are 

limitations concerning respiration depth and breathing pattern. The aim of 

this study was to evaluate the impact of video-coaching as a biofeedback tool 

to achieve more regular breathing and - as a consequence - quality improvements 

of the 4D-CT scans as well as increasing duty cycles. 

Materials: Varian RPM-gating system is used for acquisition of the CT-Scan 

(4D-CT) as well as the treatments; for the latter it manages the controlled 

switching of the radiation beam during a pre-selected specific phase of the 

respiratory cycle. 80 patients with gated treatments have been analyzed, 

whereas 40 were only audio-coached and 40 audio-coached with videofeedback. 

The video-coached group consisted of 20 patients who underwent 

treatment in free breathing mode and 20 patients who have chosen end inspiration 

voluntary breath hold technique for their treatment. We evaluated 

periodicity and amplitude variations (relative to the reference amplitude) as 

well as compliance with regard to the theoretically calculated duty cycle and 

determined the dependency of the parameters on the coaching type. 

Results: For the CT acquisitions several changes has been observed, i.e. 

fluctuations of the inspiration maxima are significantly smaller (p=0.005) and 

the breathing curves are smoother. Maxima variations were 20.78 +/- 9.98% 

with audiocoaching and 9.23 +/- 4.03% with videocoaching. Minima variations 

showed no significant changes. The compliance during the treatment 

course was significantly increased: almost all video-coached patients 

reached in average their theoretical duty cycle, whereas 60% of the patients 

with audio-coaching only had more than 25% longer treatment times due to 

inappropriate amplitudes. Periodicity is not dependent on the kind of coaching 

(p=0.01). 

Conclusions: Video-coaching is suitable to significantly improve the quality 

of 4D scans and allows optimizing the treatment time due to better compliance. 

We implemented this feedback technology combined with voluntary 

end inspiration breath hold technique allowing the patient to control the treatment 

themselves in a direct way. This approach can suit the individual patient 

need in a better way. 

1421 poster 

WHAT EFFECT HAVE THE ANATOMICAL STRUCTURES DEFINED IN 

THE ALIGNMENT CLIPBOX FOR OESOPHAGEAL TUMOURS WHEN 

USING AUTOMATIC REGISTRATION METHODS FOR CONE-BEAM 

CT VERIFICATION? 

A. Aitken 1 , V. Hansen 2 , H. McNair 1 , D. Tait 3 , M. Hawkins 3 

1 

ROYAL MARSDEN HOSPITAL (SUTTON), Radiotherapy, Sutton, United 

Kingdom 

2 

ROYAL MARSDEN HOSPITAL (SUTTON), Physicis (Radiotherapy), Sutton, 


3 

ROYAL MARSDEN HOSPITAL (SUTTON), Clinical Oncology, Sutton, United 

Kingdom 

Purpose: Accurate treatment delivery is essential to enable a reduction in 

planning target volume (PTV) margins and dose escalation. Kilo-voltage 

cone-beam CT (CBCT) provides detailed 3D soft-tissue and bone information 

facilitating accurate verification. The aim of this study was to evaluate the 

effect of clipbox definition using different anatomical structures on automatic 

CBCT image registrations using Elekta synergy software. 

Materials: Patients undergoing radical chemo radiation for oesophageal cancer 

had CBCT scans fractions 1-3 and weekly thereafter. A no action level 

(NAL) protocol was used and corrections made for any systematic errors 

greater than 2mm. Corrections were based on an automatic ’grey’ value 

match with the clipbox encompassing the PTV (clipbox 1). Retrospectively 

four image registration methods were evaluated using the automatic matching 

algorithms. The additional clipbox volumes defined were carina (clipbox 

2), vertebral bodies (clipbox 3) covering the length of PTV, as an equivalent to 

megavoltage portal imaging and all bony anatomy (clipbox 4). For PTV and 

carina, the ’grey’ value registration was used, and the automatic ’bone’ algorithm 

was used for the other two. The set-up corrections for clipbox 1 were 

compared to the corrections using clipbox 2, 3 and 4. 

Results: 10 patients each with 8 CBCT scans were evaluated giving a total 

of 80 scans each registered with 4 different clipbox positions. The percentage 

of registrations where a different correction would be made using clipbox 2, 

3 and 4 compared to clipbox 1 are shown in figure 1. In over 26% of scans, 

the automatic ’bone’ matching resulted in incorrect registrations when using 

clipbox 3. A greater correlation in the sup/inf direction was found when comparing 

clipbox 1 and 2 however 22.5% of scans showed poor correlation. A 

better correlation in the rt/lt and ant/post direction was shown between clipbox 

1 and 4 with only 18.8% and 17.5% of scans not correlating respectively. 

Clipbox 2 and 4 did not correlate in 25%, 27.5% and 37.5% of scans in the 

rt/lt, sup/inf and ant/post directions respectively. 

Conclusions: Oesophageal tumours are challenging to see on 3D imaging 

therefore reliable surrogates are needed for accurate tumour registration. In 

this study clipbox 3 did not give reliable and accurate representation of tumour 

position. The variation in set-up errors using the two automatic registration 

algorithms over four different volumes of interest highlights the need for 

further work to define the optimal alignment clipbox for CBCT image guided 

radiotherapy for oesophageal tumours. The carina could be a good surrogate 

in mid oesophageal tumours however patient specific clipbox volumes may 

be required for accurate registration. Additional studies are currently being 

undertaken exploring correlation with MV imaging and other fusion software 

(Syntegra). Figure 1. 

1422 poster 

WINSTUN-LUTZ TEST FOR STEREOTACTIC RADIOSURGERY AND 

RADIOTHERAPY DELIVERED WITH BRAINLAB MICRO MULTILEAF 

COLLIMATORS- TATA MEMORIAL HOSPITAL EXPERIENCE OF NINE 

YEARS. 

R. Kinhikar 1 , R. Jalali 2 , D. Deshpande 1 , S. K. Shrivastava 2 , R. Sarin 3 , 

K. Dinshaw 2 

1 TATA MEMORIAL HOSPITAL, Medical Physics, Mumbai, India 


3 ADVANCED CENTRE FOR TREATMENT RESEARCH AND EDUCATION IN 

CANCER, Radiation Oncology, Navi Mumbai, India 

Purpose: The Arteriovenous Malformation (AVM) and Gliomas are well managed 

by Stereotactic radiosurgery (SRS) and Stereotactic radiosurgery (SRT) 

treatment modality delivered with either linear accelerator (LINAC) based Xknife 

or gamma knife. Since a very high dose (20-25 Gy) is delivered in 

a single fraction for SRS, stringent pre-treatment quality assurance checks 

must be performed to verify the isocenter accuracy. SRS and SRT treatment 

thus demands high precision quality assurance checks. The objective of this 

paper was to analyze the results of Winstun Lutz test performed since last 

nine years to check the isocenter accuracy with BrainLAB micro multileaf collimators 

(mMLC). 

Materials: A dual energy (6 and 15 MV) linear accelerator, Clinac 2100CD 

(Varian Medical Systems, Palo Alto, USA) was installed and commissioned 

in 1999 at Tata Memorial Hospital. The LINAC is equipped with 26 pairs of 

mMLC (BrainLAB Systems, Munich, Germany) projecting 3 mm at isocenter 

with 10 cm x 10 cm field size. Till date, 62 patients were treated with SRT 

while 34 patients diagnosed with AVM were treated with SRS. All the patients 

were planned with BrainScan (V 5.2) three dimensional treatment planning 

system (3DTPS). The isocenter verification was performed for each patient 

prior to the treatment. Winstun-Lutz test was performed which ensures the 

isocenter accuracy if the 4 mm lead sphere lies inside the 6 mm square field 

size. An X-OMAT (Kodak Eastman, Rochester, NY) radiographic film was 

used for this test. 80 monitor units (MU) were delivered per field. The test 

was performed for (static Gantry and variable couch angle, variable gantry 

and static couch angle). Two exposures were from the patient plan. Total 10 

exposures were performed. The film was analyzed for isocenter accuracy. 

Results: For all the patients, the test was qualifying thus inferring the isocenter 

accuracy within + 1 mm. The mMLC positions were acceptable during 

beam eye view verification for each treatment position. 

Conclusions: The Winstun-Lutz test for all 96 patients was acceptable and 

the isocenter was found within + 1 mm. The LINAC delivered safe and conformal 

treatment with mMLC. Even after nine years of clinical use, the mMLC 

are capable to deliver accurate treatment for SRS.

RADIOBIOLOGY : COMBINED CHEMO/TARGETED AGENTS AND RADIOTHERAPY 

Radiobiology : Combined 

chemo/targeted agents and radiotherapy 

1423 poster 

COMBINATION OF EGFR/HER2 TYROSINE KINASE INHIBITION 

BY BIBW 2992 WITH IRRADIATION IN FOUR HUMAN PANCREATIC 

CARCINOMA CELL LINES 

F. Huguet 1 , N. Giocanti 2 , C. Hennequin 3 , A. Larsen 4 , V. Favaudon 2 , C. 

Louvet 5 

1 HÔPITAL TENON, APHP, Radiation Oncology, Paris, France 

2 INSTITUT CURIE, INSERM U612, Paris, France 

3 HÔPITAL SAINT LOUIS, APHP, Radiation Oncology, Paris, France 

4 UNIVERSITÉ PIERRE ET MARIE CURIE, INSERM U893, Paris, France 

5 HÔPITAL SAINT ANTOINE, APHP, Medical Oncology, Paris, France 

Purpose: Pancreatic carcinoma has a very poor prognosis. This tumor 

shows a high frequency of KRAS gene mutations. Epidermal growth factor 

receptor (EGFR) and HER2 have been reported to be both dysregulated in 

this cancer. To investigate in vitro the effect of the dual EGFR/HER2 (ErbB2) 

tyrosine kinase inhibitor BIBW 2992 on proliferation and clonogenic cell survival 

of four human pancreatic carcinoma cell lines expressing various EGFR 

and HER2 levels and to evaluate the effect of BIBW 2992 on the radiation 

response. 

Materials: Cell proliferation, cell-cycle distribution and clonogenic cell survival 

after irradiation were assayed with and without BIBW 2992 in vitro in 

BxPC-3, MiaPaCa-2, Panc-1 and Capan-2 human pancreatic carcinoma cell 

lines. The effect of the BIBW 2992 on HER receptor phosphorylation was 

also studied in vitro by Western blot analysis. 

Results: BIBW 2992 significantly increased the doubling time of the four pancreatic 

carcinoma cells lines in vitro. A marked dose-dependent antiproliferative 

effect was found in BxPC-3 (KRAS wild type) and Capan-2 (KRAS 

mutated) cell lines, which expressed the highest level of EGFR and HER2. 

Incubation with BIBW 2992 for 24 hours before and 24 hours after irradiation 

marginally increased radiosensitivity of BxPC-3 cells in vitro. For the 

three other cell lines, the interaction between radiation and BIBW 29992 was 

strictly additive. 

Conclusions: BIBW 2669 showed a clear antiproliferative effect in vitro, 

whereas radiosensitization was only marginal. The antiproliferating effect 

varied according to the level of expression of EGFR and HER2. Further investigations 

are needed to understand the role of KRAS gene mutations in 

radiosensitivity of EGFR and HER2 overexpressing cells. 

1424 poster 

DO ANTIOXIDANTS DISTURB THE EFFECT OF RADIOTHERAPY 

ON TUMOUR? 

L. Myrland 1 , A. M. Opgård 1 , E. Sundqvist 1 


Purpose: Many cancer patients take antioxidants supplements with the hope 

of improving the outcome of conventional therapies, while many oncologists 

are of different opinions meaning that antioxidants undermine the free radical 

mechanism of radiotherapy and therefore decreases the effect of radiation 

on tumour cells. Some hospitals are giving the advice to patient not to take 

antioxidants supplement during the course of radiotherapy. Our study was 

conducted to determine whether supplementation with antioxidants had influence 

on the effect of radiation on tumour volume. 

Materials: Four populations of mice had implanted prostate tumor cells in the 

flank. " One control group was given no radiation nor antioxidant " One group 

was given radiation, but no antioxidants" One group was given radiation and 

one single antioxidant (beta-carotene)" One group was given radiation and a 

mixture of antioxidantsOne week before the experiment started, and during 

the whole experiment, the mice were fed daily p.o (feedingtube) with betacarotene 

(0.4 mg/kg) or an extract of coffee, walnut, thyme, turmeric, cacao 

and vaccinium myrtillus mixt with corn oil. The feeding procedure was expected 

to cause no pain. After one introduction week with antioxidant feeding, 

the mice were given one fraction of radiotherapy. In the next three weeks the 

tumor volume was measured two times a week to watch the possible effects 

of antioxidants together with radiotherapy. 

Results: The results are under preparation and will therefore be presented 

at the conference. 

Conclusions: The conclusions of supplementation with antioxidants during 

radiotherapy will be presented at the conference. 

1425 poster 

S 453 

IN VITRO EFFECT OF RADIATION, ANTIBODY TO EGFR, DOC- 

ETAXEL AND THEIR COMBINATIONS IN HUMAN HEAD AND NECK 

SQUAMOUS CELL CARCINOMA (HNSCC) WITH MUTANT P53 AND 

OVER-EXPRESSED NORMAL EGFR 

N. Laytragoon-Lewin 1 , H. Ustun 2 , J. Castro 3 , S. Friesland 4 , M. Ghaderi 

3 , J. Lundgren 5 , I. Turesson 1 , F. Lewin 6 

1 UPPSALA UNIVERSITY, Department of Oncology, Uppsala, Sweden 

2 ESKILSTUNA HOSPITAL, Oncology, Eskilstuna, Sweden 

3 KAROLINSKA HOSPITAL, CCK, Stockholm, Sweden 

4 KAROLINSKA HOSPITAL, Oncology, Stockholm, Sweden 

5 KAROLINSKA HOSPITAL, ENT, Stockholm, Sweden 

6 SWEDISH MATCH AB /RYHOV HOSPITAL, Oncology, Stockhom/Jönköping, 

Sweden 

Purpose: Radiotherapy is the most frequently used and cheapest form treatment 

both for curative and palliative purposes in HNSCC. Despite advances 

in technology and intensive treatments with radiation, only half of the patients 

are cured. In an effort to improve patient survival and quality of life, new 

therapeutic approaches focusing on the molecular mechanism that mediate 

tumour cell growth or cell death in combination with radiotherapy have been 

suggested. As the model, in vitro effects of radiation, antibody to EGFR and 

Docetaxel as single treatment or in combinations on HNSCC cells were analysed. 

Materials: The established HNSCC cells with mutant (mt) P53 and overexpressed 

normal EGFR was used as the in vitro model. Gene expression 

profile, cell cycle progression and cell death were used as the indication of 

treatment outcome. 

Results: With c-DNA microarray of well-characterized functional genes, massive 

changes in the genes expression of HNSCC were detected. The alterations 

of gene expression profiles do not have any correlation neither on tumour 

cell growth nor cell death. HNSCC cells with mtP53 and over-expressed 

normal EGFR did not response to radiation, anti-EGFR monoclonal antibody 

and their combination therapy. Effective treatment, indicated by cell cycle arrest 

and cell death, could be obtained from single therapy with Docetaxel. No 

additive effects on cell cycle arrest or cell death were seen in the combination 

of Docetaxel to anti-EGFR antibody, radiation or anti-EGFR antibody + 

radiation. 

Conclusions: The c-DNA microarray analysis does not indicate any specific 

target or treatment effects of HNSCC with mt P53 and over-expressed normal 

EGFR. Single therapy, target at microtubules might be the most suitable 

treatment modulation in this tumour type. 

1426 poster 

INHIBITORY EFFECT OF CETUXIMAB ON RADIATION-RESISTANT 

A431 CELLS: AN IN VIVO MODEL 

G. Pueyo 1 , R. Mesia 2 , A. Lozano 3 , S. Vazquez 2 , G. Capella 1 , J. Balart 4 

1 

CATALAN INSTITUTE OF ONCOLOGY, Translational Research Laboratory - 

IDIBELL, L’Hospitalet de Llobregat, Spain 

2 

CATALAN INSTITUTE OF ONCOLOGY, Medical Oncology, L’Hospitalet de 


3 

CATALAN INSTITUTE OF ONCOLOGY, Radiation Oncology, L’Hospitalet de 


4 

CATALAN INSTITUTE OF ONCOLOGY AND HOSPITAL DE LA SANTA CREU 

I SANT PAU, Translational Research Laboratory - IDIBELL, L’Hospitalet de 

Llobregat , Spain 

Purpose: The benefit of cetuximab (C225) in the treatment of locally advanced, 

recurrent, and metastatic head and neck tumors has previously 

been reported and its use in maintenance therapy after radiotherapy is now 

emerging as a potential adjuvant treatment. However, the activity of C225 in 

radiation-resistant tumor cell repopulation has yet to be demonstrated. The 

aim of this study is to evaluate this hypothesis in an in vivo model. 

Materials: The EGFR-overexpressing A431 human tumor cell line growing 

as monolayer was cultured for 3 weeks. During this period, cells received 

one of the following treatment schedules: a) no treatment; b) 30 nM C225 

alone for 7 days; c) irradiation alone [4 fractions of 2 Gy separated by 24 h]; 

d) 30 nM C225 for 3.5 days before and during irradiation; e) 30 nM for 3.5 

days before and during irradiation and for 10 additional days, and f) 90 nM 

C225 as in schedule e. Cells were allowed to repair damage and to repopulate 

the cell culture while killed cells were removed during medium renewal. 

Finally, monolayer cell cultures were tripsinised and single cells were plated 

to determine clonogenic resistant fraction. To test activity of C225, an equivalent 

burden of radiation-resistant cells was subcutaneously injected into nude 

mice which were then treated either with saline serum or C225 (0.1 mg/mouse 

3.5 days before cell injection and 0.05 mg/mouse intraperitoneally at intervals 

of 3.5 days until sacrifice). The mice were not irradiated. Tumor growth was 

compared using the log-rank test. The mice were sacrificed when tumor volume 

(V) reached 1000 mm 3 . Micro vessel density (MVD) was evaluated by 

immunohistochemistry against the endothelial CD31 marker. 

Results: Overall, 209 out of 216 mice were successfully xenografted. The 

time, in days, to V=100 mm 3 in saline-treated mice following in vitro condi-

S 454 RADIOBIOLOGY : DNA REPAIR 

tioning was as follows: schedule a) 7.86 ± 1.61; b) 5.63 ± 0.44; c) 4.82 ± 

0.35; d) 5.07 ± 0.32; e) 4.62 ± 0.37, and f) 4.44 ± 0.39; while in C225treated 

mice, V=100 was as follows: a) 14.28 ± 1.73; b) 15.16 ± 3.61; c) 

16.94 ± 2.80; d) 11.30 ± 1.13; e) 13.93 ± 1.59, and f) 13.49 ± 1.77. Delays 

in time to V=100 mm 3 , as well as to V=500 mm 3 and V=1000 mm 3 (data not 

showed), were significant (p=0.001) in all C225-treated mice, regardless of 

in vitro conditioning. In tumors measuring 1000 mm 3 , no differences in MVD 

were seen in any of the groups analyzed. However, preliminary analysis of 

tumors whose volume was 100 mm 3 and which were derived from irradiated 

cells showed a lower MVD in C225-treated mice compared to saline-treated 

mice (39.47 ± 3.04 versus 27.80 ± 2.29; p= 0.031). 

Conclusions: In this in vivo model, C225 demonstrated a high activity 

against radiation-resistant A431 cells. This preclinical study supports the 

evaluation of adjuvant treatment with C225 after radiotherapy in EGFRdependent 

tumors. 

1427 poster 

RADIOSENSITIZING AND GROWTH INHIBITORY EFFECTS OF THE 

PTP1B INHIBITOR SURAMIN IN FADU CELLS 

P. Ohneseit 1 , H. Löffler 1 , H. P. Rodemann 1 

1 DIVISION OF RADIOBIOLOGY AND MOLECULAR ENVIRONMENTAL RE- 

SEARCH, Department of Radiation Oncology, Tübingen, Germany 

Purpose: PTP1B acts as a key insulin receptor and leptin receptor phosphatase, 

and is required for normal rates of EGFR and PDGFR dephosphorylation 

in fibroblasts. PTP1B is also proposed to influence the Ras/ERK 

pathway. The purpose of this study was to investigate the role of PTP1B in 

modulating radiation-stimulated membrane receptor activities in K-Ras wildtype 

and mutated cells. 

Materials: Wildtype and K-Ras mutated FaDu cells, as well as A549 cells 

have been treated with suramin (0.1, 0.5, 1.0 mM) every 3 days, and counted 

for determination of proliferation rates. Western Blot analysis of PTP1B expression 

as well as total and phosphorylated EGFR and AKT have been performed 

after different time periods (6, 18, 24 h) of treatment with suramin 

(0.1, 0.5, 1.0 mM) alone and in combination with EGF, TGF-α and insulin. To 

investigate radiosensitizing properties of the PTP1B inhibitor cells were pretreated 

with suramin (0.05, 0.1, 0.2 mM) prior to irradiation with single doses 

(1, 2, 4, or 6 Gy) and twice during colony formation assay. Surviving fractions 

were determined after 10 days. 

Results: Treatment with suramin led to a dose dependent growth inhibition in 

A549 and FaDu cells. However, both FaDu wildtype and K-Ras mutated cells 

displayed a strikingly higher sensitivity towards suramin compared to A549 

cells. Time- and concentration dependent phosphorylation of EGFR and AKT 

after suramin treatment alone and in combination with EGF stimulation was 

detected by Western Immunoblotting in A549 cells. However, insulin induced 

phosphorylation was reduced by suramin treatment. In EGF stimulated FaDu 

cells phosphorylation of EGFR was strikingly higher after suramin treatment, 

and was accompanied by phosphorylation of AKT. Interestingly, the amount 

of total EGFR was reduced with increasing suramin concentration. This was 

observed after treatment with EGF, TGF-α, and insulin. Radiation response 

i.e. clonogenic cell survival of A549 and FaDu cells was differentially affected 

by suramin. 

Conclusions: Treatment with the PTP1B inhibtor suramin affected radiation 

response differentially in a concentration-dependent manner in FaDu and 

A549 cells. The observed increase in tyrosine phosphorylation of EGFR after 

suramin treatment alone and particularly in combination with EGF stimulation, 

resulting in activation of the PI3K/AKT pathway, most likely can be explained 

with the inhibitory effect of suramin on dephosphorylating activity of PTP1B. 

To confirm this, more specific PTP1B inhibitors are under investigation. 

1428 poster 

RADIOTHERAPY IN COMBINATION WITH SORAFENIB - A SUC- 

CESSFUL TREATMENT OF BRAINMETASTASES FROM RENAL 

CELL CARCINOMA. 

U. Stierner 1 , Z. Taheri-Kadkhoda 1 

1 SAHLGRENSKA UNIVERSITY HOSPITAL, Dept of Oncology„ Göteborg, 

Sweden 

Purpose: We report a single case of radiotherapy for brainmetastases from 

renal cell cancer (RCC). The patient is his own control since his first metastasis 

was irradiated before sorafenib was available and his second developed 

during sorafenib treatment. Still he responded with a complete remission after 

treatment with only 2 Gy fractions to 20 Gy. 

Materials: Our patient is a 51 years old man who in January 2005 was diagnosed 

with RCC stage IV. A nephrectomy was done but no systemic treatment 

was given due to stable disease. In October a metastasis in the third ventricle 

was diagnosed. He was treated with external beam irradiation with a three 

field technique using a 2 cm margin and with 3 Gy fractions to 30 Gy. He 

responded with stable disease. After three months of interferon treatment a 

slight regression was seen. Due to progression elsewhere the patient started 

treatment with sorafenib in October 2006. At the first evaluation three months 

later his first metastasis had regressed and showed no contrast enhancement. 

However a new lesion 2.5x3cm lateral from the right lateral ventricle 

had developed while other metstatic sites had responded very well. Due to 

partly overlapping targets we could now only treat him with 2 Gy fractions to 

20 Gy. Sorafenib was stopped three days before irradiation until three days 

after. 

Results: Two months after the radiotherapy a CT scan showed a complete 

remission with a small area with low attenuation without contrast enhancement. 

The following CTs showed some contrast enhancement in the area 

making it difficult to distinguish between recurrence or necrosis. The latest 

CT from February 2008 shows however calcifications in the area indicating a 

healing process. Treatment plans as well as consecutive CTs will be shown. 

Conclusions: The development of a new brainmetastasis during sorafenib 

treatment while other metastatic sites responded very well was probably 

caused by a lower concentration of sorafenib in the brain compaired to other 

parts of the body. The first metastasis in the third ventricle was in vicinity to 

the vascular plexus and might therfore have been exposed to a higher concentration 

of sorafenib. Animal studies have shown a potentiating effect of 

antiangiogenic agents given prior to radiotherapy by improving tumor oxygenation. 

Concomitant treatment has been less successful compaired to sequential 

treatment maybe due to cellcycle effects while sequential treatment 

might have a potentiating effect by inhibiting endothelial repair. A total dose 

of 20 Gy given with 2 Gy fractions would have no effect at all on a RCC 

metastsis. Our case is very illustrative and suggests that studies combining 

sorafenib with radiotherapy should be designed with a pretreatment followed 

by a stop of treatment during the radiotherapy and a restart of dosing postirradiation. 

Radiobiology : DNA repair 

1429 poster 

EFFECT OF N- ACETYLCYSTEINE ON RADIATION-INDUCED 

GENOTOXICITY AND CYTOTOXICITY IN RAT BONE MARROW 

C. Demirel 1 , S. Kilciksiz 2 , O. I. Ay 3 , S. Gurgul 4 , M. E. Ay 3 , N. Erdal 4 

1 

FACULTY OF MEDICINE, GAZIANTEP UNIVERSITY, Department of Biophysics, 

Gaziantep, Turkey 

2 

FACULTY OF MEDICINE, GAZIANTEP UNIVERSITY, Department of Radiation 

Oncology, Gaziantep, Turkey 

3 

FACULTY OF MEDICINE, MERSIN UNIVERSITY, Department of Medical 

Biology, Mersin, Turkey 

4 

FACULTY OF MEDICINE, MERSIN UNIVERSITY, Department of Biophysics, 

Mersin, Turkey 

Purpose: The aim of our study was to evaluate the potential radioprotective 

effects of N-acetyly cysteine (NAC) against genotoxicity and cytotoxicity and 

to compare its effect with that of WR-2721 (amifostine) using the chromosomal 

aberration (CA) and micronucleus (MN) test systems in the oxidative 

damage caused by gamma-irradiation in rat’s tibial bone marrow cells. In addition 

to these test systems, we also investigated the mitotic index (MI), and 

the ratio of polychromatic erythrocytes (PCEs) to normochromatic erythrocytes 

(NCEs). 

Materials: The rats (n=16) were divided randomly and equally into four 

groups: Control (C, received 2.2 ml saline), Radiation (R, received irradiation 

and 2.2 ml saline), R+NAC (received irradiation and 1000 mg/kg NAC) and 

R+WR-2721 (received irradiation and 200 mg/kg WR-2721) rats. All groups of 

rats in the study (R, R+NAC and R+WR-2721) received whole-body gamma 

irradiation as a single dose of 6 Gy. R rats received 2.2 ml of saline (i.p.) while 

the R+NAC and R+WR-2721 rats received 1000 mg/kg, (i.p.) NAC and 200 

mg/kg, (i.p.) WR-2721 respectively. 

Results: The rats, exposed to gamma radiation alone (group R), showed 

higher CA and frequency of MN formation when compared to control, as expected 

(p < 0.05 and p < 0.01, respectively). Group R showed higher frequency 

of CA (P=NS) and MN formation when compared to both R+NAC and 

R+WR-2721 (p < 0.05 and p

1430 poster 

IN VITRO RADIOBIOLOGICAL EFFECTS OF RADIOSURGERY AND 

CYBER-KNIFE ON HUMAN GLIOMA CELL LINES 

A. Canazza 1 , L. Fumagalli 2 , F. Ghielmetti 2 , I. Milanesi 2 , L. Brait 3 , L. 

Fariselli 4 , A. Boiardi 5 , D. Croci 1 , A. Salmaggi 5 , E. Ciusani 1 

1 

FONDAZIONE IRCCS ISTITUTO NEUROLOGICO C. BESTA, Clinical 

Investigation, Milan, Italy 

2 

FONDAZIONE IRCCS ISTITUTO NEUROLOGICO C. BESTA, Dep. of 

radiotherapy, Milan, Italy 

3 

CENTRO DIAGNOSTICO ITALIANO, Radiotherapy, Milan, Italy 

4 

FONDAZIONE IRCCS ISTITUTO NEUROLOGICO C. BESTA, Radiotherapy, 

Milan, Italy 

5 

FONDAZIONE IRCCS ISTITUTO NEUROLOGICO C. BESTA, Department of 

Neurooncology, Milan, Italy 

Purpose: Radiosurgery, frequently used in the treatment of high grade 

gliomas, is a technique designed to deliver a high dose of focused radiation 

to a defined target volume of neoplastic tissue coupled, in theory, with 

the ability to spare healthy tissue around the lesion. Radiosurgery treatment 

can be performed through stereotactic radiotherapy (Linac) or Cyber Knife, 

two different types of treatment which have similar eventual biological effects 

like necrosis and mitotic death, for single doses of 8Gy or more. Purpose of 

our study was to evaluate the radiobiological effects of Linac and Cyber Knife 

on two human glioblastoma cell lines, radiosensitive A172 and more radioresistant 

U87, after a radiation dose of 2 and 8 Gy delivered by Linac and a 

dose of 8 Gy by Cyber Knife. 

Materials: After radiation we analized the ability of cells to proliferate, to form 

colonies and to invade the extracellular matrix when cultured as spheroids. 

Besides, at different times after treatment, we estimated through Comet Assay 

the radiation induced DNA damage, through realtime PCR the regulation 

of Ku70 and Ku80 genes and also Western Blot analisys allowed us to evaluate 

Ku proteins and MMP2-9 expression. 

Results: In our experimental model the dose of 8 Gy evoked on both cell 

lines and with both Linac and Cyber Knife treatment, a strong inhibition of 

proliferation, more evident in A172 in which also 2 Gy given with Linac had a 

significant antiproliferative effect. The invasion ability, as evaluated by a Matrigel 

invasion assay, displayed differences between Linac and Cyber Knife. 

In fact, a reduction was detected after 8Gy of Linac in both cell lines, whereas 

Cyber Knife caused a rise in U87. Significant DNA damage was detected in 

both cell lines after 2 and 8 Gy (Linac). However, after 3 hours most of the 

damage caused by radiation was repaired in U87 cell line and after 6 hours 

both cell lines showed an almost complete DNA recovery. Realtime PCR 

data indicated an up-regulation of Ku70-80 genes in A172 immediately after 

treatment and a mild down-regulation after 3-6 hours. Contrarily, mRNA for 

these proteins were not regulated in U87. Western blot analysis showed only 

a slight upregulation of Ku80 in U87 at 3 hours after radiation. 

Conclusions: These data suggest that the radioresistant phenotype of U87 

is related to their ability of repairing the radiation-induced DNA damage 

quicker than A172. However, the role for DNA-PKs components Ku70 and 

Ku80 on double strand breaks repair in our model is marginal. 

1431 poster 

MEASUREMENT OF THE TIME-DEPENDENT LOSS OF GAMMA- 

H2AX FLUORESCENCE IN HELA CELLS REFLECTING REPAIR OF 

RADIATION-INDUCED DNA DOUBLE STRAND BREAKS BY LOW 

AND HIGH LET RADIATION QUALITIES 

T. Schmid 1 , G. Dollinger 2 , W. Beisker 3 , A. Hauptner 4 , V. Hable 2 , C. 

Greubel 2 , A. Friedl 5 , M. Molls 1 , B. Röper 1 

1 


Department of Radiation Oncology, Muenchen, Germany 

2 

UNIVERSITAET DER BUNDESWEHR MUENCHEN, NEUBIBERG, Institute for 

Applied Physics and Metrology, Muenchen, Germany 

3 

HELMHOLTZ ZENTRUM MUENCHEN - GERMAN RESEARCH CENTER FOR 

ENVIRONMENTAL HEALTH, Institute of Toxicology, Muenchen, Germany 

4 

TECHNICAL UNIVERSITY OF MUNICH, Physik Department E12, Muenchen, 

Germany 

5 

UNIVERSITY OF MÜNICH, Institute of Radiobiology, München, Germany 

Purpose: In order to obtain more insight into future heavy ion tumor therapy 

some features of the underlying molecular mechanisms controlling the cellular 

response to high linear energy transfer (LET) radiation are currently analyzed. 

The ion microprobe SNAKE at the Munich tandem accelerator allows 

irradiation of defined cell nuclei with single or counted ions. We analyzed the 

integrated fluorescence intensity of γ-H2AX for certain time intervals after 

irradiation which is discussed as a measure of repair kinetics of radiationinduced 

DNA double-strand breaks (DSBs) in cells. 

Materials: Two different areas of one dish, where HeLa cells grow on a Mylar 

foil, were irradiated at different time points with either 1.9 Gy of 55 MeV carbon 

ions or 5 Gy of 75 keV x-rays. 15 minutes after irradiation, the cells were 

fixed and prepared for detection of γ-H2AX fluorescence. Laser-Scanning 

Cytometry (LSC) was performed to measure the total amount of γ-H2AX fluorescence 

in at least 100 cells of the first irradiation. Fluorescence signals 

RADIOBIOLOGY : DNA REPAIR 

S 455 

from cells irradiated the second time point 15 minutes before fixation were 

used for intensity calibration, which minimizes errors caused by variation between 

different dishes. 

Results: Measurements result in a 16% decrease in γ-H2AX-signalling from 

15 min to 60 min for carbon ions and in a 43% decrease for x-rays. After 

21 hours the decrease was 77% for carbon ions and 85% for x-rays. The 

corresponding time-effect relationship can be fitted by a double exponential 

decrease with two different decay times showing a fast and slow component 

of γ-H2AX reduction. Within the accuracy of measurement the fits lead to 

the same decay times for both radiation qualities. The decay times for the 

fast and the slow component were determined to be

S 456 RADIOBIOLOGY : GENOMICS AND PROTEOMICS 

1433 poster 

SINGLE NUCLEOTIDE POLYMORPHISMS IN DNA REPAIR GENES 

PREDICT OVERALL SURVIVAL IN NON-SMALL CELL LUNG CAN- 

CER PATIENTS 

D. Butkiewicz 1 , M. Rusin 1 , J. Harasim 2 , J. Gawrychowski 3 , K. Czyzewski 

2 , M. Chorazy 1 

1 

M. SKLODOWSKA-CURIE MEMORIAL CANCER CENTER AND INSTITUTE OF 

ONCOLOGY, GLIWICE BR, Department of Tumor Biology, Gliwice, Poland 

2 

MEDICAL UNIVERSITY OF SILESIA, Department of Thoracic Surgery, 

Zabrze, Poland 

3 

MEDICAL UNIVERSITY OF SILESIA, KATOWICE, Department of General 

Surgery , Bytom, Poland 

Purpose: DNA repair mechanisms play a central role in maintaining genomic 

integrity by removal of lesions caused by endo- and exogenous damaging 

agents, e.g. environmental carcinogens, tobacco smoke, cancer chemotherapeutics 

and radiation. Polymorphic variants of DNA repair genes have been 

shown to modulate the level of DNA damage, individual repair efficiency and 

cancer risk as well as response to chemo- or radiotherapy, treatment toxicity 

and clinical outcome. The aim of the study was to evaluate prognostic importance 

of a panel of SNPs in DNA repair genes in non-small cell lung cancer 

patients. There were 10 polymorphisms selected for the analysis: for NER 

- XPD 312 and 751, XPA 5’UTR -4, XPG 1104, hHR23B 241, XPC 499, for 

BER - XRCC1 399, for DSB repair - XRCC2 5’UTR -4234, XRCC3 241 and 

5’UTR -4541. 

Materials: The study group consisted of 176 patients aged 39-76 treated 

surgically due to primary NSCLC, stages I-III. DNA was obtained from frozen, 

pathologically confirmed normal lung tissue. Genotyping was performed using 

PCR-RFLP technique. Survival curves were determined using Kaplan- 

Meier method and compared by log-rank test. Hazard ratio and 95% CI were 

estimated using both univariate and multivariate Cox proportional regression 

model. 

Results: Median overall survival in the group was 17 months. The XPA(-4) 

GA+AA and XRCC1 399 Arg/Gln and/or Gln/Gln genotypes were associated 

with a shorter survival time. Multivariate analysis indicated that XPD 312, 

XPA(-4) and hHR23B 249 polymorphisms were significant factors influencing 

overall survival of NSCLC patients studied, depending on their age at diagnosis. 

Conclusions: Our preliminary results show that specific genetic polymorphisms 

in repair genes may have an impact on lung cancer patients’ clinical 

outcome. 

Radiobiology : Genomics and proteomics 

1434 poster 

GENE EXPRESSION MICROARRAY ANALYSIS IN PREDICTING 

PATHOLOGICAL RESPONSE TO NEOADJUVANT CHEMORADIA- 

TION IN OESOPHAGEAL CANCER 

C. Gillham 1 , N. Miller 2 , F. Smith 3 , D. McDowell 3 , C. Muldoon 4 , J. 

Kennedy 5 , K. O’Byrne 5 , D. Hollywood 5 , J. Reynolds 3 

1 

ST LUKE’S HOSPITAL, Radiation Oncology, Dublin, Ireland Republic of 

2 

NUI GALWAY, Academic Surgery, Galway, Ireland Republic of 

3 

ST JAMES HOSPITAL, Academic Surgery, Dublin, Ireland Republic of 

4 

ST JAMES HOSPITAL, Department of Histopathology, Dublin, Ireland 

Republic of 

5 

TRINITY COLLEGE, Academic Unit of Clinical and Molecular Oncology, 

Dublin, Ireland Republic of 

Purpose: A complete or major pathological response to neo-adjuvant 

chemoradiation is associated with favourable outcomes for oesophageal cancer. 

This response however is achieved in less than a third of patients, and 

approaches that predict response or resistance to neoadjuvant therapy may 

present a significant advance. The potential application of gene expression 

arrays was explored in this study. 

Materials: Endoscopic biopsies from 13 patients (10 adenocarcinoma, 3 

squamous cell carcinoma) were obtained prior to neo-adjuvant chemoradiation. 

Total RNA was prepared, reverse transcribed and used to generate 

digoxigenin-labelled cRNA fragments. Samples were hybridised to whole 

genome expression microarrays (Applied Biosystems). Following data normalisation, 

with bioinformatic software, the patients were sub-divided according 

to response. The resulting gene expression profiles were validated by 

real time quantitative PCR and analysed for statistical correlation between 

methods. 

Results: Gene expression profiling was possible in samples from 11 normal 

and 13 malignant samples. Data analysis using Bioconductor-R bioinformatics 

software package and SPSS (v12.0) was performed. Four hundred 

and eleven genes differentiated benign from malignant tissue using a False 

Discovery Rate (FDR) of 0.01. 108 genes differentiated major from poor responders 

to neo-adjuvant therapy (p

etter treatment of cancer. 

Materials: Analysis of the low-molecular-weight region of the blood proteome 

by mass spectrometry (MS) methods is one of the basic approaches of clinical 

proteomics. MALDI TOF MS analysis has already been used to differentiate 

cancer profiles from benign profiles. In our study we have analyzed 

low-molecular-weight serum polypeptides (

S 458 RADIOBIOLOGY : HYPOXIA AND ANGIOGENESIS 

1439 poster 

EFFECT OF INCREASING TUMOUR HYPOXIA BY COMBRETAS- 

TATIN A4 PHOSPHATE (CA4P) ON THE UPTAKE OF A PUTATIVE 

NON-INVASIVE HYPOXIA MARKER, THE PET RADIOTRACER 

64CU-ATSM 

K. Wood 1 , D. Honess 2 , R. Paul 3 , R. Maxwell 4 , J. Wilson 4 , M. O’Doherty 

3 , P. Marsden 3 , P. Blower 3 , B. Sanghera 5 , W. L. Wong 5 , M. Saunders 6 

1 

MOUNT VERNON HOSPITAL, Marie Curie Research Wing, Northwood 


2 

UNIVERSITY OF OXFORD GRAY CANCER INSTITUTE, Northwood, Middlesex, 


3 

GUY’S, KING’S, ST THOMAS - SCHOOL OF MEDICINE, Clinical PET Centre, 


4 

UNIVERSITY OF NEWCASTLE, Northern Institute for Cancer Research, 

Newcastle, United Kingdom 

5 

MOUNT VERNON HOSPITAL, Paul Strickland Scanner Centre, Northwood 


6 

MOUNT VERNON CANCER CENTRE AND UNIVERSITY COLLEGE HOSPITAL, 

Department of Oncology, London, United Kingdom 

Purpose: CA4P was used to increase tumour hypoxia in the rat P22 carcinosarcoma 

tumour model to evaluate effect on uptake and spatial distribution 

of 64Cu-ATSM versus validated immunohistochemical hypoxia markers, pimonidazole 

(pimo) and GLUT-1. Impact of CA4P on tumour blood flow was 

assessed by dynamic contrast-enhanced MRI (DCE-MRI) and on distribution 

of 64Cu-ATSM by PET and autoradiography. 

Materials: To confirm the CA4P effect on tumour oxygenation, pO2 was measured 

with an Eppendorf probe in 6 rats treated with CA4P and 3 controls. For 

radiotracer evaluation, rats received 64Cu-ATSM (CTI RDS-112 cyclotron, 

St Thomas’s Hospital, UK) at the start of a dynamic PET scan over 1 hour 

(Siemens MicroPET Focus 220). Six rats received CA4P (10mg/kg) 3 hours 

and pimo (60mg/kg) 2 hours prior to scanning. They were compared with 10 

untreated rats receiving pimo only. A region of interest (ROI) was drawn on 

the central axial tumour slice (ASIPro VMTM) from one hour summed reconstructed 

PET data to derive SUVs (MicroPET Manager 2.2.4.0, CTI Concorde 

Microsystems). A further 12 rats received CA4P 3 hours before DCE-MRI 

(Varian) performed immediately prior to PET. The area under the Gadolinium 

(Gd) concentration curve at 90 seconds (AUC90) was the tumour blood flow 

parameter. The fixed resected tumours were sectioned (10Ym), exposed to 

a storage phosphor screen (GE Healthcare, UK) for 10 days, then autoradiographs 

were digitised (ImageQuantTM, Amersham Biosciences Ltd, UK). 

The sections were stained, digitised and a separated reference map of cells 

staining positively for pimo and GLUT-1 was produced (TRI 2, Gray Cancer 

Institute). Spatial correlation between 64Cu-ATSM autoradiography and immunohistochemistry 

was determined using a pixel-by-pixel and a 10x10 grid 

comparison. A group of 3 rats was given pimo and 64Cu-ATSM prior to CA4P 

to address concerns that prior CA4P may reduce marker delivery to tumour 

Results: Administration of CA4P lowered tumour pO2 by a median difference 

of 9.9 mmHg (95% C.I 9.5 to 10.3, p

Radiobiology : Normal tissue morbidity 

1441 poster 

A COMPARISON BETWEEN PATIENT SCORED TREATMENT 

TOXICITY (LENT-SOMA) AND QUALITY OF LIFE (EORTC-C30/C35) 

AFTER HEAD AND NECK RADIOTHERAPY. 

D. Farnell 1 , K. Ho 1 , J. Routledge 2 , M. Burns 2 , N. Slevin 2 , A. Sykes 2 , S. 

Davidson 2 

1 UNIVERSITY OF MANCHESTER, Academic Department of Radiation 


2 CHRISTIE HOSPITAL FOUNDATION NHS TRUST, Department of Clinical 


Purpose: A standard and reliable way of recording patients’ toxicity from cancer 

treatment is important. Toxicity scoring systems that are observer-based 

can be insensitive to subjective endpoints like xerostomia. A patient-based 

questionnaire based on Late Effects on Normal Tissue Subjective, Objective, 

Management and Analytic (LENT-SOMA) was compared with EORTC Quality 

of Life (QLQ) C30/35 questionnaire. We examined the sensitivity and reliability 

of the LENT-SOMA questionnaire for subjective toxicity endpoint reporting. 

Materials: The study was prospective and involved 70 patients with head 

and neck cancer. Questionnaires were completed pre-treatment and 2 years 

following radical radiotherapy. 

Results: There was good correlation when matched scales containing subjective 

endpoints common to both questionnaires (pain, dysphagia, taste alteration, 

xerostomia, trismus, hoarseness, analgesia) were compared (Spearman 

rank correlation coefficient ρ>0.6, p0.05). 

The high value of Cronbach’s α (0.787) for the LENT-SOMA questionnaire 

demonstrated its high reliability. 

Conclusions: LENT-SOMA and EORTC QLQ-C35 are similar in terms of 

sensitivity and reliability for matched subjective toxicity endpoints and sensitive 

enough to detect the difference in treatment toxicity between single or 

multi-modality cancer treatment. It is proposed that both questionnaires are 

used in the assessment of toxicity of head and neck cancer treatment as they 

provide both specific radiotherapy effects (LENT-SOMA) and generic information 

on the impact of head and neck cancer and its treatment (EORTC QLQ- 

C30/35). It is suggested that observer-based toxicity scoring systems like the 

Common Terminology Criteria for Adverse Events (CTCAE), which includes 

the LENT-SOMA items, should incorporate similar patient-based questionnaires 

for reporting of subjective symptoms. 

1442 poster 

ANALYSIS OF THE DOSE-RESPONSE RELATION OF RAT SPINAL 

CORD PARALYSIS USING AN 

M. Adamus-Górka 1 , P. Mavroidis 1 , A. Brahme 1 , B. Lind 1 

1 KAROLINSKA INSTITUTET AND STOCKHOLM UNIVERSITY, Department of 


Purpose: Radiobiological models for estimating normal tissue complication 

probability (NTCP) are increasingly used in order to quantify or optimize the 

clinical outcome of radiation therapy. A good NTCP model should fulfill at 

least three requirements: (a) it should predict the sigmoidal shape of doseresponse 

curves, (b) it should describe the volume dependence of the endpoint 

and (c) it should describe the probability of a specified response for arbitrary 

non-uniform dose delivery as accurately as possible. In recent studies 

of the volume effect of rat spinal cord after irradiation with narrow and broad 

proton beams, the authors claim that none of the existing NTCP models is 

able to describe their results. 

Materials: Published experimental data have been used here trying to explain 

the change in the effective dose (D50) causing fifty percent response 

for different field sizes. The present study was initiated to test if the induction 

of white matter necrosis in rat spinal cord after irradiation with narrow 

proton beams could be explained in terms of the mean dose to the effective 

volume of the functional subunit (FSU). The physically delivered dose distribution 

was convolved with a function describing the effective size of the FSU 

to obtain the mean dose deposited in it. This procedure allows the determination 

of the mean D50 value of the FSUs of a certain size which is of interest 

for example if the cell nucleus of the oligodendrocyte is the sensitive target. 

Results: For the homogeneous dose distributions, using the least square 

method to compare the effective doses for different sizes of the functional 

subunits with the experimental data, the best fit was obtained for a length of 

about 9 mm. For the non-uniform dose distributions an effective FSU length of 

8 mm gave the optimal fit with the Probit dose-response model. The method 

RADIOBIOLOGY : NORMAL TISSUE MORBIDITY 

S 459 

could thus also be used to explain the so called bath and shower experiments 

where a heterogeneous dose distribution is used in the convolution process. 

Conclusions: The assumption of an effective FSU size is consistent with 

most of the effects seen when different portions of rat spinal cord are irradiated 

to different doses. The effective FSU length from these experiments is 

about 8.5 ± 0.5 mm. This length could be interpreted as an effective size of 

the functional subunits in rat spinal cord, where multiple myelin sheaths are 

connected by a single oligodendrocyte and repair is limited by the range of 

oligodendrocyte progenitor cell diffusion. 

1443 poster 

CLINICAL SCORING OF XEROSTOMY CORRELATES WITH THE 

CALCULATED DOSE RESPONSE OF SALIVARY FUNCTION 

J. Collan 1 , M. Tenhunen 1 , A. Kangasmäki 1 , M. Kouri 1 , J. Heikkonen 1 , K. 

Kairemo 1 , H. Joensuu 1 , K. Saarilahti 1 

1 HELSINKI UNIVERSITY CENTRAL HOSPITAL, Department of Oncology, 

Helsinki, Finland 

Purpose: The evaluation of the dose response model based on salivary 

gland scintigraphy in prediction of subjective and objective clinical scoring 

of xerostomy after IMRT for head and neck cancer. 

Materials: Twenty patients with head neck cancer were treated with IMRT 

with intention to spare the salivary gland function. Xerostomy was scored 6 

months after radiotherapy using LENT SOMA scale. Subjective and objective 

elements of xerostomy were compared with the measured salivary flow and 

calculated flow parameter from the dose response model for salivary function. 

The model was based on functional proportions of major salivary glands 

assessed by scintigraphy before therapy and a sigmoidal dose response as a 

function of mean dose within each gland (presented in detail: Tenhunen M. et 

al: Scintigraphy in prediction of the salivary gland function after gland sparing 

intensity modulated radiation therapy for head and neck cancer. Radiother 

Oncol 2008, in press.) 

Results: We found a statistically significant negative correlation of both objective 

and subjective (figure) elements of xerostomy with the measured and 

predicted salivary flow relative to pre-treatment values. Patients that were in 

high risk to get a severe (grade≥3) subjective xerostomy could have been 

identified before radiotherapy based on the dose-response model. 

Conclusions: In our material (n=20) it was possible to predict severe 

(grade≥3) subjective or objective xerostomy by the dose response model 

based on pre-treatment scintigraphy. A prospective study with a larger number 

of patients is ongoing to confirm this finding.

S 460 RADIOBIOLOGY : NORMAL TISSUE MORBIDITY 

1444 poster 

DOSE DEPENDENT PAIN IN THE PUBIC BONE AFTER RADIO- 

THERAPY 

A. C. Waldenström 1 , C. Olsson 1 , A. Palm 2 , K. A. Johansson 2 , G. 

Dunberger 3 , H. Lind 3 , M. Al-Abany 3 , U. Olofsson 1 , E. Avall-Lundqvist 4 , 

G. Steineck 1 

1 

SAHLGRENSKA ACADEMY, Clinical Cancer Epidemiology, Oncology , 


2 

SAHLGRENSKA ACADEMY, Radiation Physics, Göteborg, Sweden 

3 

KAROLINSKA INST., Clinical Cancer Epidemiology, Oncology-Pathology , 


4 

KAROLINSKA UNIVERSITY HOSPITAL, Gynaecological Oncology, Stock- 

holm, Sweden 

Purpose: Disabling pain from the pubic bone after pelvic radiotherapy is reported 

by long-term survivors treated for gynaecological cancer. It is unclear 

if this pain is caused by absorbed dose to the pubic bone. 

Materials: In 2006 we collected data from women treated with radiotherapy 

for gynaecological cancer during 1991-2003 and from matched controls. We 

included women from two regions in Sweden; eligibility criteria were age less 

than 80 years, no experience of recurrent disease and understanding of written 

Swedish. Symptoms describing pain from the skeleton were collected by 

means of a validated postal questionnaire, containing questions about pain, 

intensity of pain and functional impairment due to pain in the pubic bone. The 

pubic bone was contoured on planning CT scans and dose distribution data 

were analyzed. 

Results: We obtained information from 649 long-term cancer survivors (response 

rate 79%) and 344 controls (response rate 72%). Dose distribution 

data could be retrieved for 546/649 women. The majority of the women, 89%, 

were treated with surgery plus adjuvant radiotherapy, while 11% received radiotherapy 

alone. Brachytherapy was given to 64% and chemotherapy to 

33% of the women. The mean follow-up from radiotherapy was 93 months 

(range 30-183 months). Information about pain, intensity of pain and functional 

impairment and their relation to dose distribution data were available in 

516/546, 501/546 and 513/546 of the women respectively. Pain in the pubic 

bone was reported by 64/516 (12.4%) of the women in the study. In the mean 

dose interval of 10-35 Gy 6/51 (11.8%) had experienced pain in the pubic 

bone, 35-45 Gy 39/333 (11.7%), 45-50 Gy 14/107 (13.1%) and >50 Gy 5/25 

(20.0%) respectively. Among the women reporting pain in the pubic bone, 

35/64 (54.7%) reported severe pain, scoring between 4 and 7 on the Visual 

Analogue Scale (VAS); of these 11/35 (31.4%) scored 6 or 7. Functional impairment 

was measured as pain from the pubic bone when walking indoors 

and was reported by 42/64 (65.6%) of the women; of these 13/42 (31.0%) reported 

weekly or daily pain. Among the controls, pain in the pubic bone were 

reported by 12/339 (3.5%); VAS scores between 4 and 7 were reported by 

9/339 (2.7%) and pain when walking indoors were reported by 6/343 (1.7%). 

Conclusions: Pain in the pubic bone is related to absorbed doses above 

50 Gy from external beam radiotherapy among studied women treated for 

gynaecological cancer. 

1445 poster 

DOSE RESPONSE EVALUATION SOFTWARE (DORES) FOR CLINI- 

CAL RADIOTHERAPY 

I. Tsougos 1 , I. Grout 1 , C. Kappas 1 , K. Theodorou 1 


Purpose: To design a user-friendly tool for fast and accurate estimation 

of normal tissue complication probabilities (NTCP’s), for the evaluation and 

comparison of radiobiological dose response models, using several statistical 

methods, which can be used as a valuable complement to clinical experience. 

Materials: The software tool named DORES (Dose Response Evaluation 

Software) has been developed using Visual Basic 6.0. The required input 

information to DORES is the dose-volume histogram (DVH) data for each patient, 

the fractionation scheme and the total dose of the therapy. Furthermore 

radiobiological parameters that characterize the specific organ being treated, 

and which are compatible with the selected radiobiological dose response 

model must be selected. Processing of the input data leads to computation 

of the NTCP values which are subsequently placed in a spreadsheet file for 

further analysis. 

Results: Computed NTCP values are stored in a spreadsheet archive, together 

with the radiobiological parameters and treatment information for each 

specific patient. Dose response curves are generated automatically for the 

radiobiological model selected. Every patient of the study population can be 

plotted on the curve since by definition their corresponding dose response 

points fall exactly on the theoretical dose-response curve, when plotted on 

the same diagram. 

Conclusions: Distributions of absorbed dose alone do not provide information 

on the biological response of tissues to irradiation, so the use of this 

software may aid in the comparison of outcomes for different treatment plans 

or types of treatment, and also aid the evaluation of the sensitivity of different 

model predictions to uncertainties in parameter values. This was illustrated in 

a clinical case of breast cancer radiotherapy. DORES can be used as a tool to 

assess the predictive power of the dose-response models when clinical outcomes 

are available subsequent to irradiation of a patient during radiotherapy. 

1446 poster 

DOSE-RESPONSE PARAMETERS OF STRICTURE IN THE PROXI- 

MAL ESOPHAGUS FROM HEAD & NECK RADIOTHERAPY 

E. Alevronta 1 , A. Ahlberg 2 , P. Mavroidis 3 , M. Al-Abany 4 , S. Friesland 5 , 

A. Tilikidis 6 , G. Sakellaropoulos 1 , G. Nikiforidis 1 , G. Laurell 7 , B. Lind 3 

1 

UNIVERSITY OF PATRAS, Department of Medical Physics, Medical School, 


2 

KAROLINSKA UNIVERSITY HOSPITAL, Department of Otolaryngology, 


3 



4 

KAROLINSKA INSTITUTET, Department of Oncology-Pathology, Division of 

Clinical Cancer Epidemiology, Stockholm, Sweden 

5 

KAROLINSKA UNIVERSITY HOSPITAL, Department of Oncology, Radiumhemmet, 


6 

KAROLINSKA UNIVERSITY HOSPITAL, Department of Hospital Physics, 

Radiumhemmet, Stockholm, Sweden 

7 

UMEÅ UNIVERSITY, Clinical Sciences, Umeå, Sweden 

Purpose: The purpose of this work is to determine the dose-response parameters 

of the relative seriality model regarding the clinical endpoint of 

esophageal stricture after head & neck radiotherapy. This is accomplished 

by associating the individual 3-dimensional dose distributions of the patients 

with the clinical follow-up findings. 

Materials: This study is based on 81 patients who received radiation treatment 

for head & neck cancer at Karolinska Hospital, Stockholm, Sweden. The 

analysis was conducted for the periods 1991-2000 and 2001-2005 because 

of the different irradiation techniques used. For each patient the 3D dose distribution 

delivered to the upper 5 cm of the esophagus (proximal esophagus) 

and the clinical treatment outcome were available. Clinical symptoms and radiological 

findings were used to assess the manifestation of radiation induced 

esophageal strictures. Stricture was diagnosed 160 months after radiotherapy. 

33 patients developed esophageal stricture and 48 were symptom free. 

These data were introduced into a maximum likelihood fitting to calculate the 

best estimates of the parameters used by the relative seriality model.

Results: For the period 1991-2000, the mean and maximum doses are 49.9 

and 61.2 Gy, respectively for the group of patients with stricture, whereas 

they are 46.3 and 64.8 Gy, respectively for the control group. For the period 

2001-2005 these values are 49.8 and 61.4 Gy, respectively for the group of 

patients with stricture, whereas they are 20.6 and 46.1 Gy, respectively for 

the control group. For the period 2001-2005 the best estimates of the doseresponse 

parameters are D50=62.3 Gy (52.4-87.3 Gy), gamma = 1.14 (0.74- 

2.28) and s = 0.11 (0.01-0.33). A statistically significant positive association of 

radiation induced esophageal stricture with the biologically effective uniform 

dose (cutoff at 50 Gy) was found (odds ratio (OR) = 13.0 with 95% confidence 

interval (CI) of 2.9-58.6). Furthermore, the relative seriality model seems to 

differentiate well the patient groups with and without stricture since in a ROC 

analysis it gives the area under the ROC curve = 0.92. 

Conclusions: Radiation induced strictures were found to have a strong volume 

dependence (low relative seriality). The estimated dose-response parameters 

can be used to predict the development of esophageal stricture. 

Significantly larger mean and maximum doses characterize the group of patients 

with stricture compared to the group of patients without stricture. 

1447 poster 

DOSE-VOLUME HISTOGRAMS ANALYSIS FOR RADIATION- 

INDUCED LIVER DISEASE (RILD) AFTER HYPOFRACTIONATED 

CONFORMAL RADIOTHERAPY FOR PRIMARY LIVER CARCI- 

NOMA(PLC)PATIENTS WITH CHILD-PUGH GRADE A CIRRHOSIS 

S. Liang 1 , J. Guoliang 2 , Z. Xiaodong 1 , C. Long 1 

1 GUANGXI CANCER HOSPITAL, Radiation Oncology, Nanning, China 

2 CANCER HOSPITAL,FUDAN UNIVERSITY, Radiation Oncology, Shanghai, 

China 

Purpose: Radiation-induced liver disease (RILD) has been considered the 

most severe complication in liver irradiation. That severity of hepatic cirrhosis 

was demonstrated to be the most important predictor for RILD. The purpose 

of the current study was to identify a dosimetric predictor for RILD in primary 

liver carcinoma (PLC) patients with Child-Pugh grade A cirrhosis when 

treated with hypofractionated conformal radiotherapy(CRT). 

Materials: Between August 2000 and June 2007, 114 patients eligible for 

this study were accrued. The median age was 45 years (23-79), and males 

predominated, with a ratio of 104 men to 10 women. Portal vein thrombosis 

(PVT) was detected in 22 patients (19%). The mean value of gross tumor 

volume (GTV) was 378.3±308.1cm3 .A median dose of 53Gy (40-68) was 

delivered to the PLC by hypofractionated CRT (three fractions per week) with 

a median fraction size of 4.6Gy (4-6). 38 cases received transcatheter arterial 

chemoembolization (TACE). All patients had full 3D treatment planning 

including liver dose-volume histograms(DVHs) prior to treatment delivery. 

Results: The median follow-up time was 19 months (1-79) after the completion 

of 3DCRT. 9(7.9%) patients were diagnosed as RILD. Univariate analysis 

revealed the gross tumor volume (GTV), and percent of the normal liver volume 

exceeding 5-40 Gy (V5-40) be statistically significant relative to the development 

of RILD. Multivariate analyses demonstrated GTV and V20 were 

independent predictors(P=0.015 and 0.003, respectively). With V20 of 48.5% 

as the tolerance, the prediction of RILD achieved high accuracy (0.763), with 

a sensitivity of 0.889 and a specificity of 0.752. 

Conclusions: The risk factors for occurrence of RILD were the GTV and V20 

for PLC patients with Child-Pugh grade A cirrhosis treated with hypofractionated 

CRT. V20 may be a useful parameter in comparing treatment plans to 

evaluate the risk of RILD for our individual patient treatment. 


1448 poster 

S 461 

DOSE-VOLUME RESPONSE ANALYSIS FOR URINARY URGENCY: 

EXTERNAL BEAM RADIOTHERAPY ALONE VERSUS EXTERNAL 

BEAM RADIOTHERAPY IN COMBINATION WITH HYPOFRACTION- 

ATED BRACHYTHERAPY 

N. Pettersson 1 , G. Steineck 2 , B. Lennernäs 3 , E. Holmberg 4 , K. A. 

Johansson 1 

1 SAHLGRENSKA UNIVERSITY HOSPITAL, Radiophysics, Göteborg, Sweden 

2 SAHLGRENSKA AKADEMIN / KAROLINSKA INSTITUTET, Department of 

Clinical Cancer Epidemiology, Göteborg / Stockholm, Sweden 

3 SAHLGRENSKA UNIVERSITY HOSPITAL, Oncology, Göteborg, Sweden 

4 SAHLGRENSKA AKADEMIN, Department of Clinical Cancer Epidemiology, 


Purpose: To investigate the dose-volume response of urinary urgency after 

radiation therapy of prostate cancer. 

Materials: At Sahlgrenska University Hospital, Gothenburg, Sweden, 

prostate cancer has been treated with either EBRT, 35x2 Gy, or with a combination 

of EBRT, 25x2 Gy, and HDR BT, 2x10 Gy. In 2001 a questionnaire was 

mailed to all patients treated with RT during 1988-97 and to an age-matched 

control group. The investigated endpoint was urinary urgency, "Yes" or No", 

as response to "In the last month, did you need to urinate again less than 

two hours after urinating on more than 40% of occasions?".The bladder was 

contoured on the CT images. To reconstruct the total dose distribution for 

EBRT+BT patients, a matching of the applicators relative anatomical landmarks 

onto the EBRT CT images was performed. Due to the nature of the 

dose distributions in the bladder of the EBRT+BT treatments, it was possible 

to use the original DVHs and the linear-quadratic model (α/β=3 Gy) to calculate 

a DVH taking fractionation effects into account.The dose to the high-dose 

volume v, Dv, was extracted from each cumulative DVH for a range of both 

absolute and relative volumes. Maximum likelihood estimation (MLE) was 

used to find the best fitting combination of v, and position (TD50) and steepness 

(γ50) of a logistic dose-response curve (DRC). Analyses of DRCs with 

and without explicitly including the response rate of the control group were 

performed. The Dvs for the best fitting v were evaluated with the area under 

the receiver operating characteristic (ROC) curve, Az. 

Results: With the criteria of returned questionnaire and complete treatment 

data, 34 patients receiving EBRT alone and 51 receiving EBRT+BT were analyzed. 

In the EBRT group 16/34 (47 %), in the EBRT+BT group 11/51 (22 

%), and in the control group 23/121 (19 %) of the responders reported the 

symptom. The best fitting DRC was found for D50cm3 regardless of whether 

the control group’s response rate was included or not. For the DRC not including 

the control group, TD50 and γ50 were 62.0 Gy and 1.2, respectively. 

An Az=0.75±0.13 (95% CI), was obtained for D50cm3 indicating good predictive 

ability. Relative volumes and the mean dose both had lower areas 

(Az


Jae 1 , A. Yong Chan 1 

1 

SAMSUNG MEDICAL CENTER, Radiation Oncology , Seoul, Korea Republic 

of 

2 

SAMSUNG MEDICAL CENTER, Department of Medicine, Seoul, Korea 

Republic of 

Purpose: To identify the dosimetric parameters that correlate with the risk 

of radiation-induced gastroduodenal toxicity (RIGDT) after three-dimensional 

conformal radiotherapy (3D-CRT) for patients with unresectable hepatocellular 

carcinoma (HCC). 

Materials: We retrospectively analyzed dose-volume histograms (DVHs) and 

clinical records of 81 HCC patients treated with 3D-CRT with a daily dose of 3 

Gy. The median dose given was 36 Gy and the grade of RIGDT was defined 

by modifying the gastritis toxicity from the Common Toxicity Criteria. The 

evaluated dosimetric parameters were the mean, maximum and minimum 

doses given to the gastroduodenum (GD) and the percentage of GD volume 

receiving more than 5, 10, 15, 20, 25, 30 and 35 Gy. To obtain a predictive 

value for grade 3 RIGDT, receiver operating characteristic curves (ROC) were 

generated. 

Results: Grade 2 and 3 RIGDT developed in 30 patients (37.0%) and 9 patients 

(11.1%), respectively. All of the parameters except the maximum and 

minimum doses significantly affected the development of grade 3 toxicity. By 

ROC analysis, V30 and V35 were the best predictors for grade 3 toxicity, and 

the optimal cut-off values were 12% and 5%, respectively. 

Conclusions: There was a dose-volume relationship in the development of 

RIGDT and administration of less radiation to a smaller GD volume may be 

the best way to prevent RIGDT. 

1450 poster 

EFFECT OF X-IRRADIATION IN RAT SUBMANDIBULAR GLAND: 

APOPTOSIS AND EXPRESSION OF AQP5 AND TGF-BETA 

H. G. Wu 1 , J. H. Choi 1 , K. C. Jung 2 , S. H. Lee 3 , E. K. Kwon 3 

1 

SEOUL NATIONAL UNIVERSITY COLLEGE OF MEDICINE, Radiation 


2 

SEOUL NATIONAL UNIVERSITY COLLEGE OF MEDICINE, Pathology, Seoul , 


3 

INSTITUTE OF RADIATION MEDICINE, MEDICAL RESEARCH CENTER, 

SEOUL NATIONAL UNIVERS, Seoul , Korea Republic of 

Purpose: To evaluate the effect of X-irradiation on apoptosis and the changes 

of morphology and expression of aquaporin 5 (AQP5) and transforming 

growth factorβ (TGF-β) in rat submandibular gland. 

Materials: The submandibular glands of male SD rat were locally X-irradiated 

in the head and neck region with a single dose of 3, 10, 20, or 30 Gy and 

analyzed apoptosis and the changes of morphology and expression of AQP5 

and TGF-β at early post-irradiation phase (1 and 8 hours and 1, 2, 3 and 

5 days after irradiation) and late post-irradiation phase (10, 20, 30 and 60 

days after irradiation). The morphological and morphometrical changes in 

the glands were assessed after H & E staining. Apoptosis was measured 

by tunnel assay and electronic microscopy. The expressions of AQP5 and 

TGF-β were identified by immunohistochemical staining. 

Results: The X-irradiated submandibular glands showed degenerative 

changes including pyknotic nuclei, vacuolization of acinar cells, lysis of acini 

and granular convoluted tubules (GCT), and interstitial edema. These degenerative 

changes were detected more frequently at high dose and a doserelated 

effect was noticed. Acinar and GCT cells number of irradiated glands 

were no significant change comparing to non-irradiated control. From 20 days 

after irradiation, increased apoptotic cells were observed and GCT and intercalated 

duct (ID) cells expressed higher apoptotic index than cells of nonirradiated 

control. Immunohistochemically, a marked decrease of AQP5 expression 

on membrane of acinar cells from 10 days after irradiation and in 

TGF-β expression on cytoplasm of GCT from 20 days after irradiation were 

seen in glands of irradiated rat comparing to that of non-irradiated control. 

Conclusions: Radiation-induced apoptosis in rat submandibular glands may 

influence to dysfunction of late post-irradiation phase. The loss of AQP 5 in 

acinar cells and TGF-β in GCT cells might be responsible for late salivary 

dysfunction. Further animal study and clinical study is necessary. 

1451 poster 

EVALUATION OF EARLY AND LATE THYROID DYSFUNCTION IN 

PATIENTS TREATED WITH RADIOTHERAPY FOR HEAD-AND-NECK 

CANCER 

M. Koc 1 

1 SELCUK UNIVERSITY MERAM MEDICAL SCHOOL, Radiation Oncology, 

Konya, Turkey 

Purpose: Aim of this study to examine thyroid dysfunction in the early and 

late phase of radiotherapy to the head and neck region. 

Materials: Sixty-three patients (54 men and 9 women) receiving neck irradiation 

including the thyroid gland were recruited in the study. Thirty-six patients 

had undergone either a functional or radical neck dissection, and radiotherapy 

was the primary treatment in 27 patients. The neck, including the thyroid, 

was irradiated using a single anterior or two lateral portals using cobalt-60 

teletherapy unit (Picker C- 9, NY, USA, before 2003) or high energy lineer accelerator 

(Primus, 6MV, Siemens, after 2003). Eligibility required that patients 

had received RT to a volume encompassing the entire thyroid gland which 

was confirmed by review of planning films. Total dose received by the thyroid 

gland was estimated to be comparable to that received by the treated volume. 

Median dose delivered to the primary treated volume was 64 Gy (range 50- 

70 Gy) and neck 54 Gy(46-54Gy) in 2 Gy per fraction, one fraction per day, 

5 days per week over 35-49 days. Statistical analysis was performed with a 

Statistical Package for the Social Sciences for Windows (SPSS, version 10.0, 

Chicago, IL, USA). All values are expressed as means and standard deviations 

(SD). Observations were compared with Student’s t-test. The time from 

the start of RT to HT was analyzed in the same way as death in ordinary survival 

analysis. The significance of differences between groups was assessed 

by the Mantel-Haenzel (log-rank) test. Multivariate analyses as well as univariate 

analyses of continuous factors were analyzed with Cox regression. P 

values < 0.05 were considered to indicate statistical significance. Patient age, 

neck RT dose and clinical stage were examined as grouped variables for this 

evaluation : < 60 years vs. ≥ 60 years old and 60 Gy vs. ≥ 60 Gy, stage II 

vs. stage III and IV. 

Results: Of sixty-three patients, twenty-four (38 %) were diagnosed with hypothyroidism 

(HT), 8 (12.7%) with clinical HT and 16 (25.4%) with subclinical 

HT. The median time to the development of clinical HT was 15 months (range, 

0-36 months) and subclinical HT 3 months (range, 0-24 months). Eleven of 

the patients (17.5%) were diagnosed with subclinical hyperthyroidism. The 

median time to the development of the subclinical hyperthyroidism was 0 

months (completion of RT) (range, 0-3 months). Upon completion of radiotherapy, 

compare to preradiotherapy, there was a significant decrease in 

the TSH levels in both the operated and non-operated patients (at p=0.001 

level), and significant decrease in TSH level in in-operated group at the end of 

3 months (at p=0.002 level). Furthermore, compared to pre-treatment, there 

was a significant decrease in the level of FT3 (p= 0.003) in operated cases but 

no difference in the FT4 levels (p=0.44). In overall evaluation of the patients, 

TSH level was observed significantly decreased on completion of RT and 12, 

24 and 36 months compared to before radiotherapy. Univariate and multivariate 

analyses of age, smoking history, neck RT dose, clinical stage, concurrent 

chemotherapy and surgery failed to identify a clinically relevant risk factor for 

HT. Univariate analysis of clinical HT revealed that the elevated pre-RT TSH 

level was significant factor (p=0.021). Multivariate analysis showed that patients 

with surgery (p=0.027) and females (p=0.024) had higher risk of HT. 

Clinical and subclinical manifestations of early and late radiation toxicity were 

observed in the thyroid. 

Conclusions: The incidence of overt HT after locoregional RT for nonthyroid 

head-and-neck cancer continues to increase with time, even after long-term 

follow-up. We recommend that thyroid function should be evaluated periodically 

in patients who have undergone neck radiation. 

1452 poster 

PREDICTIVE FACTORS OF SYMPTOMATIC RADIATION-INDUCED 

LUNG INJURY IN PATIENTS TREATED WITH STEREOTACTIC BODY 

RADIATION THERAPY FOR LUNG TUMOURS 

U. Ricardi 1 , A. R. Filippi 2 , A. Guarneri 2 , F. Giglioli 3 , C. Mantovani 2 , C. 

Fiandra 1 , S. Anglesio 3 , R. Ragona 1 

1 

UNIVERSITA DI TORINO, Radiation Oncology, Torino, Italy 

2 

A.S.O.U. S. GIOVANNI BATTISTA DI TORINO, Radiation Oncology, Torino, 

Italy 

3 

A.S.O.U. S. GIOVANNI BATTISTA DI TORINO, Medical Physics, Torino, Italy 

Purpose: The aim was to retrospectively investigate correlations between 

different predictive parameters and the occurrence of symptomatic radiationinduced 

lung injury in patients with stage I non-small cell lung cancer 

(NSCLC) or lung metastases treated with stereotactic body radiation therapy 

(SBRT). 

Materials: Sixty patients (63 tumours) underwent SBRT, with a dose of 45 

Gy in 3 fractions over 5 days (47 NSCLC, 11 metastases) or 26 Gy in single 

fraction (5 metastases). The following parameters were considered for the 

statistical analysis and tested for correlation with Radiation Therapy Oncology 

Group (RTOG) lung toxicity score: planning target volume (PTV), tumour 

location (more centrally located vs. peripheral), primary vs. metastatic tumours, 

lobe (inferior vs. median vs. superior), and Mean Lung Dose (MLD). 

Normal Tissue Complication Probability (NTCP) values were calculated and 

employed for radiobiological modelling. 

Results: The median follow-up time was 30.9 months (range 6.7-56.7). 

RTOG grade 0-1 pulmonary toxicity was observed globally in 54/63 lesions 

(85.7%) and grade 2-3 in 9/63 (14.3%). On the whole cohort, median NTCP 

was 1.1% (range 0.1-36%) and median MLD was 5.05 Gy (range 2.1-11.5 

Gy). Median values of NTCP in grade 0-1 and 2-3 RP were respectively 1% 

(range 0.1-10%) and 9% (range 2.6-36%). Median values of MLD in grade 

0-1 and 2-3 RP were respectively 4.8 Gy (range 2.1-9.7 Gy) and 9.8 Gy (7.2- 

11.5 Gy). Polythomous regression analysis showed a strong correlation between 

radiation pneumonitis RTOG score and MLD (p=0.001), and a trend 

of correlation between radiation pneumonitis RTOG score and more central

tumours’ location (p=0.087). From dose-response relationship between observed 

pneumonitis rate and absolute MLD (not corrected for fractionation) 

we obtained a D50 value of 9.6 Gy and a γ50 value 2.66, while from the 

dose-response relationship between calculated NTCP and MLD a D50 value 

of 11.85 Gy and a γ50 value of 3.99. 

Conclusions: MLD is strongly associated to the risk of developing lung injury 

in thoracic SBRT. Higher NTCP values were associated with a higher risk, but 

when comparing the expected toxicity rate to the observed rate, NTCP seems 

to underestimate the absolute risk of toxicity. 

1453 poster 

QUANTIFICATION OF RADIATION-INDUCED LOCAL DAMAGE IN 

RAT LUNG FROM COMPUTED TOMOGRAPHY 

G. Ghobadi 1 , H. Faber 1 , J. M. Schippers 2 , S. Brandenburg 3 , J. Langendijk 

1 , R. Coppes 4 , P. van Luijk 1 

1 

UNIVERSITY MEDICAL CENTER GRONINGEN, Department of Radiation 


2 

PAUL SCHERRER INSTITUT, Accelerator department, Villigen-PSI, 

Switzerland 

3 

KERNFYSISCH VERSNELLER INSTITUUT, Groningen, Netherlands 

4 

UNIVERSITY MEDICAL CENTER GRONINGEN, Section of Radiation and 

Stress Cell Biology, Department of Cell Biology, Groningen, Netherlands 

Purpose: In clinical radiotherapy, prediction of pulmonary damage is based 

on the assumption that local damage in the lung depends on local dose only. 

However, we showed that other factors, like lung region and co-irradiation of 

the heart, may impact the relation between local dose and a clinical complication. 

To further investigate the relation between dose and local damage, it 

is necessary to quantify local changes in the lung. Recently, we developed 

an approach to quantify changes in large lung regions from CT images and 

demonstrated that this quantity correlates to changes in global organ function 

(1). In the present study, this method was modified to allow quantification of 

local changes for each position in the lung independently. The study aimed to 

develop a method that allows in vivo quantification of local radiation damage 

to the rat lung, to demonstrate that this method is capable of quantifying radiation 

effects in the lung, and to correlate local damage to changes in global 

organ function loss. 

Materials: Radiation ports were designed using planning CT scans of 5 agematched 

animals. 100% of rat lungs were irradiated with 9-12.2 Gy using 150 

MeV protons. As a measure of global function, breathing rate was measured 

before and every 2 weeks after irradiation. To assess structural changes CT 

scanning was performed before and at 8 weeks after irradiation. 

Results: Delineation of the lungs in the CT scans using a computerized algorithm 

ensured objectivity. Relating changes of the mean and standard deviation 

of the density (in hounsfield units) within 1 mm3 sub-volume of the delineated 

lung, with values obtained in the same subvolume in non-irradiated controls 

yielded to one quantitative measure for local structural change,. These 

local changes in the lung tissue were dose dependent and correlated to global 

function. 

Conclusions: This new method can be used for in vivo quantification of local 

radiation-induced changes in the lung. It may enable us to determine a 

relation between local radiation effects and loss of global function in partial 

irradiated lung volume and provide supportive information to further develop 

a predictive model for radiation-induced loss of lung function. Analysis of the 

response to non-uniform irradiations is ongoing. (1) van Luijk P et al. Int J 

Radiat Oncol Biol Phys. 2006; 64:1495-02 


1454 poster 

S 463 

RENAL TOXICITY FROM ALPHA-RADIOIMMUNOTHERAPY WITH 

ASTATINE-211: A LONG TERM STUDY IN NUDE MICE 

T. Bäck 1 , R. Hultborn 2 , H. Kahu 2 , S. Lindegren 1 , E. Warnhammar 2 , L. 

Jacobsson 1 

1 SAHLGRENSKA ACADEMY AT THE UNIVERSITY OF GOTHENBURG, Dep of 

Radiation Physics, Gothenburg, Sweden 

2 SAHLGRENSKA ACADEMY AT THE UNIVERSITY OF GOTHENBURG, Dep of 


Purpose: The effects from high-LET irradiation on the kidneys after RIT with 

the alpha emitter astatine-211 was studied functionally in nude mice by repeated 

measurements on GFR using plasma clearance of Cr-51-EDTA. Not 

only the bone marrow, but also the kidney is a dose limiting organ in internal 

radiotherapy. In this study, the renal toxicity following alpha-RIT was evaluated 

on a functional endpoint at levels close to the dose limit for the bone 

marrow. 

Materials: Renal toxicity from intravenously administered astatine-211 labeled 

MX-35-F(ab’)2 monoclonal antibody was studied on a long-term basis 

in nude mice. The study was carried out on non-tumor carrying animals, but 

also included was data from a population of animals carrying s.c. xenografts 

of the human ovarian cancer cell line OVCAR-3. The animals received 0.4, 

0.8, or 1.4 MBq at one, two, or three repetitions. Mean absorbed dose to 

kidneys was estimated from a separate biodistribution study and ranged from 

1.5 Gy up to 15 Gy. Depending on the growth, the tumors were surgically removed 

after 40 to 80 days, making possible a long-term study of these tumor 

carriers as well. The renal function was studied repeatedly by GFR measurements 

on the same individual up to 67 weeks after first treatment. Other data 

collected on renal toxicity included urine analysis, serum creatinine, urea and 

cystatine C. At the time of sacrifice the kidneys were collected and sections 

made for histological examination with light microscopy. 

Results: The repeated GFR-measurements were divided in 6 time intervals 

after treatment and related to mean absorbed dose to the kidneys. The dose 

required for a 50% reduction in GFR decreased with time from approx. 16 Gy 

at 8-10 weeks to 8 Gy after 42-50 weeks. A dose-dependent effect on GFR 

was found already at 8-10 weeks, with a percentage reduction in GFR of 

3.2% per Gy. For the intervals 13-19, 21-25, 34-38, 42-50 and 52-67 weeks 

after treatment the corresponding reduction was 3.4%, 4.4%, 3.9%, 6.6% 

and 5.6% per Gy, respectively. The serum creatinine levels showed a dosedependent 

increase from 12.8 ± 0.65n mikromol/L for untreated controls to 

21.4 ± 0.75n mikromol/L at 15 Gy. Histological examination revealed that 

pathological findings were present, for both tubular and glomerular compartments, 

although typically not severe. 

Conclusions: After alpha-RIT with the alpha emitter astatine-211, at levels 

close to the dose limit for the bone marrow, a clear dose-effect on GFR was 

found. A mean absorbed dose to the kidneys of 8 Gy resulted in a reduction 

on GFR of 50% at 42-50 weeks after treatment. 

1455 poster 

STEM CELL TRANSPLANTATION TO RESCUE RADIATION- 

DAMAGED SALIVARY GLANDS 

R. Coppes 1 , I. Lombaert 1 , M. Stokman 2 , J. Brunsting 1 , H. Kampinga 1 , 

G. de Haan 3 


Department of Radiation and Stress Cell Biology, Groningen, Netherlands 


Oral Maxillofacial Surgery, Groningen, Netherlands 


Department of Stem Cell Biology, Groningen, Netherlands 

Purpose: Radiationinduced damage to salivary glands may lead to xerostomia 

(dry mouth syndrome) and severely compromise the quality of life of 

cancer patients. As the current treatments and prevention techniques of xerostomia 

are insufficient and not applicable to all patients, there is need for 

novel strategies. Adult stem cell transplantation may be used to replace radiation 

sterilised stem cells and restore salivary gland function. In this study 

the potential of salivary gland stem cell therapy was investigated. 

Materials: Male eGFP + stem cells were isolated from mouse submandibular 

glands (SMG) and enriched by an in vitro floating sphere culture. Subsequently, 

flow cytometry was used to sort c-Kit + cells, which were injected in 

irradiated female mice submandibular glands. Two months after transplantation, 

salispheres were cultured from SMG of primary recipients and male 

eGFP + donor-derived c-Kit + cells were transplanted in irradiated SMG of secondary 

female recipients. Immuno-histochemistry and flow rate measurements 

were used to determine the success of transplantation. Similarly, stem 

cells were isolated from human SMG. 

Results: Transplantation of a limited number of c-Kit + duct cells, obtained 

from day 3 cultured (sali)spheres, in irradiated submandibular glands resulted 

in the development of donor-derived ductal and acinar structures and longterm 

restoration of salivary gland function. Donor derived c-Kit + cells from 

spheres obtained from responder mice rescued salivary glands from secondary 

irradiated recipients suggesting the selfrenewal capacity of cells in


this population. Similar to the mouse model, human parotid and submandibular 

gland cells were cultured as salispheres. In time, duct cells in the human 

salispheres differentiated in vitro into acinar cells. Additionally, a small fraction 

of c-Kit + cells was present in human spheres. These results suggest that 

a similar ’putative’ stem cell population can be isolated from human salivary 

glands. Future research will focus on the functional stem cell capacity of the 

c-Kit + cells, both using in vitro assays and in vivo transplantation in immunodeficient 

mice. 

Conclusions: This is the first proof for potential use of stem cell transplantation 

to functionally rescue solid organ deficiency after radiotherapy. Supported 

by grants of the Dutch Society for Cancer Research and the EU KP-6 

project FIRST. 

1456 poster 

THE EFFECT OF VITAMIN D PROPHYLAXIS ON RADIATION 

INDUCED PULMONARY DAMAGE 

G. Yazici 1 , F. Yýldýz 2 , A. Ýskit 3 , E. Erdemli 4 , P. Fýrat 5 , M. Hayran 6 

1 

ANKARA EDUCATION AND RESEARCH HOSPITAL, Radiation Oncology, 


2 

HACETTEPE UNIVERSITY FACULTY OF MEDICINE, Radiation Oncology, 


3 

HACETTEPE UNIVERSITY FACULTY OF MEDICINE, Department of Pharmacology, 


4 

ANKARA UNIVERSITY FACULTY OF MEDICINE, Department of Histology 

and Embryology, Ankara, Turkey 

5 

HACETTEPE UNIVERSITY FACULTY OF MEDICINE, Pathology, Ankara, 

Turkey 

6 

HACETTEPE UNIVERSITY FACULTY OF MEDICINE, Department of Preven- 

tive Oncology, Ankara, Turkey 

Purpose: The antineoplastic activity of vitamin D was first shown in mouse 

myeloid leukemia cells. In vitro and in vivo studies have shown the growth 

inhibitory effect of vitamin D on breast, colon, prostate, endometrial, bladder, 

pancreas cancer and osteosarcoma cell lines. It has also been demonstrated 

that vitamin D has a selective radiosensitizing effect on cancer cells 

without any such effect on fibroblasts. The aim of this experimental study 

was to investigate whether vitamin D has a protective effect in radiation induced 

pulmonary damage. The rats were treated with 20 Gy single dose 

right hemithorax radiotherapy and the effect of prophylactic vitamin D treatment 

on radiation induced pneumonitis and fibrosis was evaluated by light 

and electron microscopic studies. 

Materials: For this purpose, adult Wistar rats were divided into 4 groups. 

The first group comprised control animals. The second group, which was administered 

0.25 µgr/kg/day vitamin D3 for 8 weeks, was the vitamin D control 

group. The rats in the third and fourth groups were given 20 Gy right hemithorax 

radiotherapy. The fourth group was given vitamin D3 treatment in addition 

to radiotherapy, starting from the day before the radiotherapy until the end of 

the eighth week. Four animals from each group were sacrificed at the eight 

and twelfth weeks for morphologic examinations with light microscopy and 

electron microscopy. 

Results: Light microscopic examinations performed at the eighth and twelfth 

weeks did not reveal any statistically significant differences between the radiotherapy 

control group and the radiotherapy plus vitamin D3 therapy group 

with regard to edema, bleeding, total interstitial cell count, macrophage infiltration, 

interstitial and perivascular mast cell count and, fibrosis. However, 

there was a significant difference between radiotherapy groups and the control 

ones regarding these parameters. Nevertheless, the electron microscopic 

examinations showed decreased interstitial inflammation and collagen deposition 

in the vitamin D group and, alveolar structure and the cells lining the 

alveolar walls were found to be protected. 

Conclusions: In conclusion our study reveals that vitamin D may have a 

potential beneficial effect in the prevention of radiation induced pneumonitis 

and pulmonary fibrosis. We think that it is worthy to perform clinical studies 

to confirm these experimental findings. 

1457 poster 

THE EFFECTS OF GINKGO BILOBA ON SKIN DAMAGE INDUCED 

BY RADIATION: AN EXPERIMENTAL STUDY 

E. Yirmibesoglu 1 , E. Karahacioglu 1 , D. Unsal 1 , N. Lortlar Ucankus 2 , G. 

Akbulut 3 , S. Omeroglu 2 

1 GUTF, Radiation Oncology, Ankara, Turkey 

2 GUTF, Histology and embryology, Ankara, Turkey 

3 GUTF, Physiology, Ankara, Turkey 

Purpose: Adverse effects caused by radiotherapy (RT) on surrounding normal 

structures can necessitate interruption of treatment and, as a result, can 

lead to lowered tumoral control rates. In this experimental study, the aim was 

to investigate the potential protective effects of the use of ginkgo biloba (GB) 

in the setting of dermatitis secondary to RT. 

Materials: Male Wistar albino rats were randomized into 4 to represent control, 

drug, RT and drug+RT groups. In the drug group, GB was administered 

intraperitoneally at a dose of 100mg/kg/day through days 1 to 5. On day 5, 

RT was administered to both lower extremities such that the skin dose was 

36Gy. Using the skin biopsy at 18 hours following RT, gluthation (GSH), malondialdehyde 

(MDA) ve nitric oxide (NOx) levels were studied. Following sacrification 

at day 21 following RT, a semi-quantitative dermatitis score of the 

skin tissue was calculated using 4 parameters (edema, epidermal atrophy, 

hair follicle loss, collagen loss). On immunohistochemical evaluation (IHC), 

the staining intensity (none-0, mild-1, moderate-2, strong-3) and the staining 

percentage (50%-diffuse) was evaluated 

for proliferative cellular nuclear antigen (PCNA) ve transforming growth factorbeta3 

(TGF-β3). IHC was regarded as positive when the multiplication of the 

two scores was >2. 

Results: A decrease of 7% in RT group as compared to control and an increase 

of 12% in RT group as compared to drug+RT group was observed in 

GSH level (p

1459 poster 

XRCC1 AND XRCC3 GENES POLYMORPHISMS IN ASSOCIATION 

WITH EARLY NORMAL TISSUE MORBIDITY AFTER RADIOTHER- 

APY FOR GYNECOLOGICAL MALIGNANCIES 

E. Encheva 1 , I. Yordanova 2 , T. Lackov 2 , R. Kaneva 2 , A. Savov 2 , Z. 

Zahariev 1 , B. Sultanov 1 , I. Kremensky 2 , T. Hadjieva 1 

1 UNIVERSITY HOSPITAL "QUEEN GIOVANNA", Radiotherapy, Sofia, Bulgaria 

2 MEDICAL UNIVERSITY, Molecular Medicine Center, Sofia, Bulgaria 

Purpose: To exam the association of the early morbidity after pelvic irradiation 

for gynecologic malignancy with five polymorphisms in two DNA repair 

genes XRCC1 (Codon 194 Arg/Trp; Codon 280 Arg/His; Codon 399 Arg/Gln) 

and XRCC3 (Codon 241 Thr/Met; IVS5-14 17.893). 

Materials: The study included 125 women with cervical or endometrial cancer 

selected from 2005 to 2008. External beam radiotherapy was delivered 

to all patients as primary or adjuvant treatment after surgery. The total dose 

ranged from 50 to 56 Gy. The NCI CTCAE v.3.0 was implemented to measure 

the early gastrointestinal and genitourinary systems reactions. DNA was isolated 

from venous blood and Polymerase chain reaction-restriction fragment 

length polymorphism (PCR-RFLP) analysis was performed for genotyping. 

Two patients’ reactions groups were defined: "no or slight reactions" (grade 0 

and 1) and "moderate and severe reactions" (grade 2 and 3). 

Results: Seventy seven patients experienced moderate and severe gastrointestinal 

reactions, while 48 patients had no or slight reactions. The moderate 

and severe genitourinary reactions were found in 48 patients and 77 patients 

had no or slight reactions. No grade 4 reactions were seen in the series. 

The XRCC1 Codon 280 Arg/His polymorphic allele was significantly associated 

with the acute genitourinary morbidity. A significant protective role was 

found for the G/G genotype, while the mutated allele increase the radiosensitivity 

(p=0,0045). For the rest of the investigated XRCC1 and XRCC3 gene 

polymorphisms no significant associations were found. 

Conclusions: The present study supports the involvement of XRCC1 in the 

occurrence of early genitourinary reaction after gynecologic pelvic irradiation. 

On the contrary XRCC3 analysis did not show any correlation. 

Radiobiology : Others 

1460 poster 

A COMPARISON OF THE RISK OF INDUCTION OF SECOND 

TUMORS AMONG: DCRT, LINAC IMRT AND TOMO HT IRRADIATION 

RADIOBIOLOGY : OTHERS 

MODALITIES, IN THE HEAD AND NECK AND PELVIC REGIONS 

R. Calandrino 1 , G. M. Cattaneo 1 , S. Broggi 1 , C. Fiorino 1 

1 H.S. RAFFAELE, Department of Medical Physics, Milano, Italy 

S 465 

Purpose: The effective balance of the quality of a treatment course, is a complex 

evaluation where tumour coverage OAR’s doses and DVHs ratio have to 

be primarely considered. For long term surviving patients and/or pediatric 

treatments, as last but not least, the risk of 2nd tumour induction is becoming 

a parameter to be also taken in consideration when rival plans are under 

evaluations. The evaluation and the comparison of 2nd tumour induction risk, 

by means of the most reliable models available in litterature, have been carried 

out comparing the dosimetric data of 3 different irradiation modalities : 

3DCRT, IMRT and HT in the neck and pelvic region. 

Materials: 5 Patients for Neck 6 patients for prostate tratment have been 

planned in the 3 different modalities. The dose and OAR’s costraints used 

for forward and inverse planning where assumed from palnning routine . The 

differential DVHs have been used as input data for the formula of the OED, 

as defined by the Schneider’s model for the RT volume. Depending by the 

model assumed for the risk evaluation (linear, bell shaped or plateau), 3 different 

values will be obtained for the OED. Whereas the secondary radiation 

intensity measured at 50 cm from the center of the fields at 10 cm depth has 

been considered for the out field body dose The sum of the out field body 

dose with the OED values is calculated and the risk of 2nd tumor induction 

consequentely calculated using the factor 2,5E-02/Gy. 

Results: 

Conclusions: The set of data so far analyzed demonstrates an increase in 

the mean OED for TOMO HT when compared to 3DCRT or Linac IMRT. A 

detailed data analysis is now in progress and final results and comments will 

be available before september 08. 

1461 poster 

A PHASE I/II TRIAL OF DENDRITIC CELLS IMMUNOTHERAPY 

COMBINED WITH IRRADIATION IN THE ADVANCED COLORECTAL 

CANCER WITH MULTIPLE LIVER METASTASES 

H. S. Lee 1 , H. J. Choi 2 , Y. M. Choi 1 , H. C. Kwon 3 , D. W. Kim 1 

1 

DONG-A UNIVERSITY HOSPITAL, Radiation Oncology, Busan, Korea 

Republic of 

2 

DONG-A UNIVERSITY HOSPITAL, Surgery, Busan, Korea Republic of 

3 

DONG-A UNIVERSITY HOSPITAL, Hemato-oncology, Busan, Korea 

Republic of 

Purpose: To assess the toxicity and tumor response induced by DCVac/IR R○ 

dendritic cells (DCs) immunotherapy combined with irradiation for advanced 

colorectal cancer patients with multiple liver metastases. 

Materials: Between May 2004 and Nov 2006, applicants among the refractory 

colorectal cancer patients with multiple liver metastases were enrolled. 

Patients were registered after having signed the informed consent form, which 

had been approved by the Institutional Review Board from Dong-A and Busan 

National university hospital. DCs were obtained from the peripheral blood of

S 466 RADIOBIOLOGY : OTHERS 

each patient, and then cultured in vitro. 6x10 6 DCs were packed into a vial 

(DCVac/IR R○ , 0.5 ml) in accordance with the schedule of each patient. One 

day before and on the day of each vaccination, patients received each 4 Gy 

radiation therapy to the target tumor. On the day of vaccination, the indicated 

dose of autologous DCs was injected into the irradiated tumor using 

ultrasound-guided needle injection procedures. A total of four vaccinations 

were scheduled at intervals of three consecutive 2 weeks and one 4 weeks 

in the Dong-A university and Busan national university hospital. If the tumor 

status was deemed to be stable or responding to therapy, an additional one or 

two more vaccinations were approved at intervals of 4 weeks after the fourth 

immunization. Tolerance test was conducted from 3x10 6 DCs to 12x10 6 DCs 

after the 3th injection, and then the maximal tolerable dose was applied to 

additional patients. Safety was evaluated in all patients who had at least one 

injection. Feasibility was tested at the 10th week by means of response evaluation 

for the patients having at least 4 injections. For systemic toxicities, 

the National Cancer Institute Common Toxicity Criteria was used. Adverse 

effects were recorded using common WHO toxicity criteria. 

Results: Twenty two out of 24 registered patients received the DCs injections. 

Among 14 patients applied for the tolerance test, 11 patients completed it because 

3 patients withdrew their agreement for the test. A grade 3 or more 

side effect, potentially related to the DCs injection, did not happen in additional 

patients. The level of 12x10 6 DCs was identified as the tolerable dose, 

and then 12x10 6 DCs were injected in additional 8 patients. Patients tolerated 

fairly, and a fatal side effect was not found. In order to assess the feasibility of 

DCs immunotherapy, the response was evaluated in the other hepatic lesion 

outside the targeted hepatic lesion. Among 17 patients receiving at least 4 

injections, response evaluation was performed in 15 patients. The stable and 

progressive disease were found in 4 and 11 patients, respectively. 

Conclusions: The DCs-based immunotherapy and radiotherapy is theoretically 

synergistic in local control and systemic control. The DCVac/IR R○ immunotherapy 

combined with irradiation was tolerable and safe in the refractory 

colorectal cancer with multiple liver metastases. A well designed a phase 

II clinical trials are needed. 

1462 poster 

ASSESSMENT OF DOSE ESCALATION IN PARTIAL LIVER RT 

WITH DEFORMABLE MOTION MODELS AND BIOLOGICAL PLAN 

OPTIMISATION. 

C. Coolens 1 , M. Long 2 , D. Tait 2 , M. Hawkins 2 

1 

ROYAL MARSDEN HOSPITAL TRUST & INSTITUTE OF CANCER RESEARCH, 

Physics, London, United Kingdom 

2 

ROYAL MARSDEN HOSPITAL TRUST & INSTITUTE OF CANCER RESEARCH, 

Radiotherapy, London, United Kingdom 

Purpose: To investigate the benefits of margin reduction for partial liver irradiation 

using MRI-derived motion models and the possibility of dose escalation 

using the effective normal liver volume (Veff) as a parameter. 

Materials: Plans were generated for 7 patients using liver and tumour motion 

information from 4D MRI data and fluoroscopy 1 . A total of 10 fractions 

over 10 days were prescribed. Total dose delivered varied form 30Gy to 40 

Gy. Retrospectively the plans were re-optimised to a reduced volume, PTVR 

= CTV + 5mm, which includes the set-up error and motion prediction accuracy. 

Dose escalation was then attempted in 5 Gy increments to 50 Gy, whilst 

maintaining the same dose constraints for liver (V30, V50) and OAR: small 

bowel, stomach, duodenum, kidneys, spinal cord etc. Veff was calculated for 

all clinical and experimental plans. 

Results: Using the reduced PTV margins from the motion model the original 

PTV volume [mean= 350cc; range 52 670 cc] was reduced by 23% [8.4 

49%]. This resulted in the possibility to dose escalate by an average 11.4 Gy 

[0 20 Gy; stdev = 7 Gy]. In half the cases the escalation was limited by nonliver 

OAR constraint violations. The resulting Veff was reduced on average 

by 11.2% [8.1 18.8%] with the median normal liver volume being 1450 cc 

[1035 1807 cc]. A constant linear relationship was visible between Veff and 

the prescribed dose although the slope of the curve was smaller for the two 

smallest tumour cases. 

Conclusions: An increased therapeutic ratio can be seen using the MRI 

derived motion model for partial liver RT although similar results would be 

obtained for other stereotactic techniques that reduce the tumour motion to 

within 5mm. Plan optimisation according to Veff shows a linear relationship 

with possible dose escalation and toxicity although more data is needed to 

statistically confirm the exact correlation value. 1 Free breathing liver gated radiotherapy 

with external markers using MRI derived models of hepatic motion", 

2007, Coolens C., M White, D Hawkes, D Atkinson, L Charles-Edwards, 

D Tait, M Hawkins, Proceedings XVth ICCR, p496. 

1463 poster 

CALCULATION OF ABSOLUTE RISK OF SECONDARY MALIGNAN- 

CIES FROM A RANGE OF DIFFERENT TREATMENT TECHNIQUES 

G. Webster 1 , S. Smith 1 , C. Rowbottom 1 , R. Mackay 1 

1 CHRISTIE HOSPITAL NHS TRUST, North Western Medical Physics, 

Manchester, United Kingdom 

Purpose: Major changes to the planning and delivery of radiotherapy 

have occurred in recent years as technological advances such as intensitymodulated 

radiotherapy (IMRT), Tomotherapy and, more recently, intensitymodulated 

arc therapy (IMAT) have offered improved solutions to problems 

such as organ sparing and the limitations on escalating dose. However, limited 

consideration has been given to the potential detrimental effects of these 

advances. This work quantifies the increased potential of these techniques 

to induce secondary malignancies in the patient. 

Materials: A 3D conformal plan, a 7-beam IMRT plan and an IMAT-simulation 

plan have been created for the same head and neck patient in the Pinnacle 

TPS with a prescribed dose to PTV1 of 65Gy. A further IMAT-simulation incorporating 

a simultaneous boost to PTV1 to 85Gy has also been planned. 

Dose distributions have been calculated on an extended dataset that models 

the full patient to determine the doses from in-patient and collimator scatter 

to the entire patient volume. Leakage dose, which is not modelled in Pinnacle, 

has been determined throughout the patient volume using the relevant 

IEC tolerance, an ISL correction and the monitor units required for each plan. 

The absolute risk of cancer-induction has been calculated using the equation 

where N is the number of dose points within the patient and R(Di) is the risk 

associated with the dose (leakage + scatter) at point i. A range of risk models 

have been used to calculate the absolute risk of inducing a secondary cancer 

for each technique (see Figure 1). 

Results: The resulting absolute risks of inducing a secondary cancer are 

shown in Table 1 using each of the three risk models applied to all plans. 

Risk models A and B result in significantly lower risk as they assume a low 

risk in high dose regions. These values of risk are not felt to be sufficiently 

high to offset the benefits of the advanced techniques. 

Conclusions: The absolute risk of cancer-induction has been evaluated for a 

range of treatment techniques for a head and neck case. This work will be extended 

to incorporate organ-specific radiosensitivities into the risk calculation 

and to include a range of treatment sites and treatment techniques.

1464 poster 

COMPLEX DNA DAMAGE IN RELATION TO CELL CYCLE POSITION 

AFTER EXPOSURE TO LOW-LET OR HIGH-LET RADIATION 

K. Magnander 1 , K. Claesson 1 , H. Kahu 1 , R. Hultborn 1 , K. Elmroth 1 

1 SAHLGRENSKA ACADEMY, UNIVERSITY OF GOTHENBURG, Department of 


Purpose: 211 At is an α-particle emitting radionuclide that has become of 

clinical interest as a potential agent for cancer treatment of small tumours 

and micrometastases due to radiophysical properties. The purpose of this 

project is to investigate the relative effect of α-particles from 211 At on the cell 

nucleus in detail. In this study we have used 211 At and X-ray to investigate 

the induction of complex DNA damages. Earlier we have shown that the 

chromatin structure influence the induction of DSB and clustered damage 

after ionising radiation. Due to the chromatin structure variations during the 

cell cycle, we have investigated DNA damage induction in synchronized cells 

after exposure to ionizing radiation with low-LET or high-LET. 

Materials: Mammalian fibroblasts were synchronized with serum free 

medium followed by treatment with mimosine. Pulsed field gel electrophoresis 

with fragment analysis was used to quantify the number of DSB after 

irradiation. Clustered damages, i.e. two or more lesions located on opposite 

strands within two helical turns on DNA, were quantified as the increase in 

DSB in post irradiation incubated cells with the enzyme Fpg. Also, cell survival 

in different cell cycle phases was investigated using the clonogenic cell 

survival assay. 

Results: Preliminary data show that RBE for DNA damage induction in synchronized 

fibroblasts in G1, irradiated with 211 At, was 2 for DSB and 3 for 

clustered damages, with X-rays as reference radiation. In early S-phase, 

RBE values have increased to 5 and 4 for DSB and clusters, respectively. 

However, data show an excess of DSB and clustered damage in G1 and mitotic 

cells compared with cells in early or late S-phase, irradiated with 211 At or 

X-rays. Further, 211 At induced an excess of smaller fragments and a deficit 

of larger fragments compared with X-rays. Clonogenic survival experiment 

show that cells irradiated in G1 are more sensitive to radiation than cells in 

early and late S-phase. 

Conclusions: In conclusion, α-particles from 211 At induced two to five times 

more DSB and clustered damage than X-rays depending on cell cycle phase. 

The difference in LET seems to have a greater effect on cells in S-phase than 

in G1. The number of complex DNA damages varies during the cell cycle, 

with most damages in mitosis and in G1. This seems also to influence the 

cell survival. 

1465 poster 

DOES INCIDENTAL IRRADIATION WITH DOSES LOWER THAN 50 

GY EFFECTIVELY REDUCE ISOLATED NODAL RECURRENCES IN 

NON-SMALL-CELL LUNG CANCER: DOSE-RESPONSE RELATION- 

SHIP 

L. Kepka 1 , B. Maciejewski 2 , H. R. Withers 3 

1 M. SKLODOWSKA-CURIE MEMORIAL CANCER CENTER AND INSTITUTE OF 

ONCOLOGY, Radiation Oncology, Warsaw, Poland 


OF ONCOLOGY, GLIWICE, Radiation Oncology, Gliwice, Poland 

3 UCLA MEDICAL CENTER, Radiation Oncology, Los Angeles, USA 

Purpose: To evaluate the dose-response relationship for incidental irradiation 

of hilar and mediastinal lymph node stations in 220 patients with non-small 

cell lung cancer treated with 3-D conformal radiotherapy. The only end-point 

was isolated nodal recurrence (INR). 

Materials: The individual responses of 2596 nodal stations are analysed. Different 

fractionation schedules were used in different patients. Total prescribed 

tumour doses ranged from 48 Gy to 74 Gy given in 16-56 days. There were 

1198 nodal stations (46%) within, and 1398 stations beyond elective nodal irradiation 

(ENI) volumes. INR was defined as regional nodal failure occurring 

without local progression regardless of distant metastases status. The INR 

was estimated for doses from 5 ± 5 Gy to ≥ 55 Gy. 

Results: There were a total of 25 INR in 17 patients (8%). The incidence of 

INR within the electively treated volumes was 0.58% compared with 1.28% 

in node stations beyond the ENI. Almost 80% of INRs occurred during 10 

months of follow-up. There was a strong dose-response relationship for INR. 

With increasing 5 ± 5 Gy to 40 ± 5 Gy the rate of freedom from INR increased 

to from 12% to 76%. 

Conclusions: There is evidence of a dose-response relationship between 

reduction in the rate of INR and doses lower than 50 Gy. This suggests that 

"incidental irradiation" can eradicate at least some of subclinical metastases 

in regional lymph nodes. 

1466 poster 


S 467 

EFFECT OF HIGH PROTEIN DIET AND/OR RESVERATROL SUP- 

PLEMENT ON RADIATION-INDUCED ENTERITIS IN RAT 

S. H. Kang 1 , K. O. Kim 2 , E. Y. Lee 1 , M. Chun 1 , H. S. Kim 2 

1 

AJOU UNIVERSITY HOSPITAL, Radiation Oncology, Suwon City, Korea 

Republic of 

2 

COLLEGE OF HUMAN ECOLOGY, SOOKMYUNG WOMEN’S UNIVERSITY, 

Major in Food and Nutrition, Seoul, Korea Republic of 

Purpose: Radiotherapy to abdomen or pelvis may induce the damage to 

intestinal epithelium and change in normal physiologic function. It may ultimately 

diminish a patient’s nutritional status by interfering with absorption of 

nutrients. The aim of study was to evaluate the effect of supplementation of 

high protein diet and/or antioxidant, resveratrol on radiation-induced enteritis 

in rat. 

Materials: Female Wistar rats weighing between 180~230 g were used in 

the study. Thirty six rats were assigned randomly after pelvic radiation to 

one of four groups (9 in each group): a normal protein diet group (NP), a 

normal protein diet with resveratrol group (NP+Res), a high protein diet group 

(HP), a high protein diet with resveratrol group (HP+Res). They were fed 

with each diet for 12 days prior to radiation and continued for 10 days after 

irradiation. Six sham irradiated rats were fed with normal protein diet (C). 

Total daily caloric intake was same in all groups. All animals had free access 

to individual diets. Rats were sacrificed on 10th day after irradiation and blood 

samples from heart were acquired for the evaluation of nutritional status and 

the measurement of inflammatory cytokines level (IL-2, 6, 10, and 12). 

Results: Irradiation led to significant mean weight losses. But there were 

no differences in patterns of body weight change between four irradiated 

groups. Triglyceride (389.8±113.7 mg/dL) and LDL (13.5±2.0 mg/dL) of 

group NP were significantly higher than that of group C (89±11.5 mg/dl and 

7.5±1.7 mg/dl) while levels of protein, albumin and HDL were significantly 

decreased in group NP. With supplementations of high protein diet and/or 

resveratrol, there were no the improvement of protein and albumin status. 

However, levels of triglyceride and LDL were significantly decreased in group 

HP (229.7±89.6 and 10.8±2.1 mg/dL) and group HP+Res (153.6±41.0 

and 10.2±2.2 mg/dL). Production of IL-2 and IL-6 were significantly increased 

after irradiation (20.9±5.2 vs 5.2±0.7 pg/mL for IL-2, 204.9±41.9 vs 

115.8±35.3 pg/dL for IL-6). These values were effectively reduced in rats administrated 

high protein diet or resveratrol supplement (IL-2: 8.9±2.8 pg/mL 

in HP, 10.2±3.7 in NP+Res, and 11.9±4.1 in HP+Res, IL-6: 96.2±18.1 

mg/mL in HP, 111.5±44.0 in NP+Res, and 90.9±19.4 in HP+Res). 

Conclusions: These findings suggest that high protein diet and resveratrol 

may effectively ameliorate an alteration of absorption and metabolism of lipid 

in irradiated intestine. 

1467 poster 

EFFECTS OF SPATIAL AND TEMPORAL MODULATION OF RADIA- 

TION BEAMS ON CELL SURVIVAL 

N. Suchowerska 1 , J. Bewes 1 , D. McKenzie 2 , M. Jackson 1 , M. Ebert 3 , C. 

Milross 1 

1 ROYAL PRINCE ALFRED HOSPITAL, Radiation Oncology, Sydney, Australia 

2 UNIVERSITY OF SYDNEY, School of Physics, Sydney, Australia 

3 SIR CHARLES GAIRDNER CANCER CENTRE, Radiation Oncology, Perth, 

Australia 

Purpose: Intensity modulated radiation therapy (IMRT) treatments promise 

improved patient outcomes by more closely conforming the radiation dose to 

the tumour volume. The inherent spatial modulation of dose in IMRT makes 

the expression of non local or bystander effects more apparent. Temporal 

modulation of the dose deposited in multiple small field segments in IMRT 

introduces variability in cell survival by changing the repair dynamics. We will 

provide experimental evidence that the local dose alone is not an accurate 

predictor of response in modulated fields. 

Materials: We report on cell survival following exposure to spatially modulated 

beams, as created by multi-leaf collimators, using in vitro experiments 

with malignant melanoma (MM576) and non-small cell lung (NCl-H460) cell 

lines. The cell survival in both the shielded and unshielded regions of spatially 

modulated fields, as determined by a clonogenic assay, were compared 

to the cell survival in the uniformly irradiated fields. The effects of temporally 

modulated beams on cell survival was determined using the clonogenic 

assay and the incidence of double strand DNA breaks with the 2AX assay. 

The utility of both assays was improved by the development and use of new 

automated counting and analysis software (CHiTA). 

Results: We found that in spatially modulated fields, cell survival for both cell 

lines was influenced by the fate of neighbouring cells and can be attributed to 

one of three types of bystander effect (Claridge 2007). Temporal modulation 

within a treatment fraction was found to affect not only cell survival, but also 

the observed incidence of double strand breaks using the 2AX assay, even 

when the total exposure time and total dose were held constant. The experimental 

results confirm theoretical predictions (Altman 2006) that the dose 

history within a treatment fraction affects the treatment outcome. 

Conclusions: The opportunities presented by IMRT can only be fully realized


by taking advantage of the biological consequences of modulating dose delivery. 

both spatially and temporally. An improved understanding of the complex 

nature of tissue response to complex therapeutic irradiation will enable us to 

achieve better clinical outcomes. 

References 

Altman, M. B., Chmura, S. J., Deasy, J. O., & Roeske, J. C. (2006). Optimization 

of the temporal pattern of radiation: An IMRT based study. International 

Journal of Radiation Oncology*Biology*Physics , 898-905. 

Claridge-Mackonis, E., Suchowerska, N., Zhang, M., Ebert, M., McKenzie, D. 

R., & Jackson, M. (2007). Cellular Response to Modulated Radiation Fields. 

Physics in Medicine and Biology , 5469-5482. 

Acknowledgements: This work was supported by a research project grant 

from the NSW Cancer Council. 

1468 poster 

ESTIMATION OF TUMOUR GROWTH MODEL, TUMOUR FORMA- 

TION TIME, AND METASTASIS FORMATION RATE IN CLINICAL 

SETTINGS 

E. Mehrara 1 , E. Forssell-Aronsson 1 , V. Johanson 2 , L. Kolby 2 , H. Ahlman 

2 , P. Bernhardt 1 

1 UNIVERSITY OF GOTHENBURG, Radiation Physics, Goteborg, Sweden 

2 UNIVERSITY OF GOTHENBURG, Surgery, Goteborg, Sweden 

Purpose: The knowledge of size distribution of metastases is one important 

factor for optimization of cancer treatment. However, the size distribution of 

metastases had to be estimated by mathematical approaches, since the detection 

of micro-metastases is not possible with modern medical devices. If 

the growth model of metastases is known the number and size distribution 

of all metastases, including undetected micro-metastases, can be estimated. 

The standard method to find the growth model of tumors is by direct model 

(curve) fitting, where different growth models are fitted to the volume of each 

individual tumor and the best fitting can be selected. However, uncertainties 

in volume estimation and limited amount of clinical observations make it difficult 

to distinguish different growth models by direct model fitting. The aim of 

this study was to develop a technique for estimation of tumor growth model in 

clinical studies. 

Materials: The growth model of tumor was estimated by analysis of the relationship 

between tumor growth rate and its volume. The form of this relationship 

was defined for the Gompertzian and the power-law models. The 

new method as well as the standard curve fitting method was applied to two 

sets of clinical observations: liver metastases from a primary small intestine 

(midgut) carcinoid tumour and lung metastases from a primary renal cell carcinoma. 

The applicability of this method was further studied by finding the 

tumour formation times and metastasis formation rate. 

Results: Direct model fitting gave non-realistic results, but the presented 

method could estimate a general growth model for each patient that could 

well describe the growth of all metastases of the same type and in the same 

host tissue in each patient. The increase in the number of metastases by 

time could be described by exponential curves for the three models. The 

metastasis formation rate was similar for the Gompertzian and the power-law 

models, which was higher than for the exponential model. 

Conclusions: In conclusion, the introduced method can be used for a more 

correct (compared to the standard curve fitting) estimation of tumour growth 

model, tumour formation time, and metastasis formation rate in clinical studies 

1469 poster 

EVALUATION ON THE FOUR-DIMENSIONAL RADIATION TREAT- 

MENT PLAN FOR LUNG CANCER USING BIOLOGICALLY 

EFFECTIVE UNIFORM DOSE 

F. C. Su 1 , C. Shi 1 , P. Mavroidis 2 , A. Gutierrez 1 , N. Papanikolaou 1 


2 KAROLINSKA INSTITUTE AND UNIVERSITY OF STOCKHOLM, Medical 


Purpose: The goal of this study is to apply biologically effective uniform dose 

(BEUD) on the four-dimensional (4D) radiation treatment plan for a lung patient 

and to compare this 4D treatment plan with MLC-based intensity modulated 

radiation therapy (IMRT) plans for fixed respiratory phases. 

Materials: One lung cancer case, which was previously planned using 

stereotactic body radiotherapy (SBRT) technique, was chosen to re-plan with 

the 4D radiotherapy technique using the Pinnacle3 treatment planning system. 

This 4D treatment plan was developed based on a set of 4DCT images 

which were divided into ten respiratory phases. We defined the planning target 

volume (PTV) by expanding the gross target volume (GTV) (about 12 cm 3 ) 

with a 5 mm margin uniformly around it. The target dose in each plan was 

normalized so that 95% of the PTV received 48 Gy. Both physical dose statistics 

and BEUD calculations were performed to evaluate the final composite 

4D dose distribution. 

Results: Dose volume histograms (DVHs) for the composite 4D plan and 

IMRT plans for different breathing phases were shown in figure 1. From DVH 

comparisons, target coverage of different plans did not show significant differences. 

Dose sparing to the normal lung around the PTV was similar between 

the 4D plan and other IMRT plans for fixed phases. From BEUD calculation 

results, the complication-free tumor control probability, P+ value, was 78.6% 

for the 4D plan with a mean dose of 49.9 Gy to PTV and the BEUD of 49.9 

Gy as well. The total control probability, PB, is 98.5% and the total complication 

probability, PI, is 20% due to high maximum dose to the lung, which is 

proximal to the PTV. When compared with fixed-phase IMRT plans, the dose 

distributions were very similar; the P+ value of the 4D plan, however, was 

higher, but was not substantially different from values of fixed-phase plans. 

Conclusions: We performed both physical and biological analysis to comprehensively 

evaluate the composite 4D plan. The 4D plan was superior, but 

not significant improved from MLC-based IMRT plans for fixed phases. Not 

only the mean doses to PTV of these plans were very close, but also were 

P+ and BEUDs of these plans. Possible reasons for this result might be attributed 

to the small volume of the target. Dose distributions of the 4D plan 

can be further optimized to a maximum P+ of 86.5% when achieving BEUDB 

of 42.95 Gy by sparing the lung to make PI reach as low as 7.2%. 

1470 poster 

IN VITRO STUDY OF RADIATION BYSTANDER EFFECT IN GLIOMA 

CELLS 

M. Martinou 1 , E. Giannopoulou 2 , G. Malatara 3 , D. Kardamakis 1 

1 

UNIVERSITY OF PATRAS MEDICAL SCHOOL, Radiation Oncology, Rion 


2 

UNIVERSITY OF PATRAS MEDICAL SCHOOL, Medical Oncology, Rion 


3 

UNIVERSITY OF PATRAS MEDICAL SCHOOL, Medical Physics, Rion Patras, 

Greece 

Purpose: The bystander effect refers to the induction of biological effects 

in cells that are not directly traversed by a charged particle. The bystander 

effect can be initiated experimentally, by using low linear energy transfer radiation, 

harvesting culture medium from irradiated cells and transferring to 

unexposed cells, and by sophisticated single particle microbeams. We studied 

the bystander effect of radiation in glioma cells by using low doses of 

radiation. 

Materials: The glioblastoma cell line LN18 was exposed to various doses of 

radiation ranging from 0.5 to 15 Gy (SL75 Philips, 6MV). Twenty four hours 

after the irradiation, we studied apoptosis using the annexin V binding assay. 

Forty-eight hours after the irradiation, proliferation and MMP-2 secretion were 

evaluated by MTT assay and zymography, respectively. The levels of phosphorylated 

EGFR were estimated using an ELISA kit, 15 min after irradiation. 

Results: We found that 48h after radiation, cell proliferation decreased with a 

dose dependent manner. In line with these results is the increase in apoptosis 

that was observed 24h after radiation. In contrast, EGFR was activated 15 

min after radiation and MMPs levels were increased 48h after radiation. 

Conclusions: Although low doses of radiation exert an inhibitory effect in 

cell proliferation and increase apoptosis, this effect may change in latter time 

points. More experiments are needed for elucidating the molecular pathways 

that bystander effect alters. 

1471 poster 

IRRADIATION OF HUMAN SERUM AND PLASMA WITH HIGH DOSES 

L. Jüling-Pohlit 1 , K. Eberlein 2 , G. Hintereder 1 , C. Rödel 1 

1 

JOHANN WOLFGANG GOETHE UNIVERSITY, Radiotherapy and Oncology, 

Frankfurt, Germany 

2 

JOHANN WOLFGANG GOETHE UNIVERSITY, Department of Internal 

Medicine, Frankfurt, Germany

Purpose: In 2006 we had a patient with lassa fever. For measuring blood 

parameters for STAT (short turn around time) lab it was necessary to be sure 

that the blood was free of virus. Elliot and Mc Cormick published in 1982 

that it is possible to inactivate lassa virus by gamma irradiation with a dose 

of 15.000 Gy. In this paper we investigated whether irradiation with such 

high doses is a practical method to prepare blood for stat lab or if the blood 

components are destroyed by high doses. 

Materials: Serum and plasma samples of 50 patients were taken, mixed and 

pooled. Samples( of one millilitre each) were aliquoted into eppendorf tubes 

and frozen immediately at -86 ◦ C. Two serum and plasma samples were measured 

at this time to get an initial value. Altogether 22 serum parameters and 

6 plasma parameters were measured. The frozen samples were irradiated 

and measured within 24 hours to exclude the influence of time on the change 

of parameters. We irradiated with 5000, 10000, 15000, 20000 and 40000 Gy 

electrons generated by a 10 mev accelerator (IBA) at BGS in Bruchsal. 

Results: The measured serum parameters were constant up to 20.000 Gy. 

Only at 40.000 Gy did the radiation dose influence the parameters. For the 

plasma parameters the results were dose dependent .To correct these values 

a polynomial was searched 

Conclusions: It is possible to get virus free blood for STAT lab samples by 

irradiation with high doses. In Germany there are enough accelerators (i.e. at 

BGS) to irradiate blood samples within short time without logistical problems. 

1472 poster 

LOW-DOSE HYPER-RADIOSENSITIVITY: A CELLULAR AUTOMATA 

MODEL 

M. Partridge 1 

1 THE INSTITUTE OF CANCER RESEARCH, Joint Department of Physics, 


Purpose: Experimental evidence shows that some types of cell exhibit a high 

degree of sensitivity to small single doses of ionizing radiation, but become 

more resistant to larger doses (per unit dose); this phenomenon is low-dose 

hyper-radiosensitivity. It has been hypothesised that this effect may be due to 

failure of the ATM-dependent repair process to fully arrest the progression of 

damaged G2-phase cells into mitosis below some threshold dose (and therefore 

damage) level. The aim of this work is to investigate low-dose hypersensitivity 

to radiation using a cellular automata model which explicitly includes 

damage-dependent checkpoints at the end of G1 and G2 phases. 

Materials: Our model represents stratified squamous epithelium (e.g. oesophagus, 

rectum and oropharynx; all important dose-limiting tissues in radiotherapy) 

using a 2D tessellation of Voronoi polygons, each representing 

a cell. Cells cycle with the transition times from G1, S, G2 and M phases 

sampled from probability distributions typical of human epithelium and are 

motile, seeking to move away from regions of overcrowding. Radiation damage 

is simulated stochastically by counting radiation "hits" per cell (a "hit" 

represents irreparable, potentially-lethal DNA damage). 1 hit/cell triggers G2 

arrest, 3 hits/cell triggers G1 arrest and 5 hits/cell leads directly to cell death. 

Any damaged cell attempting mitosis has a finite probability of incurring further 

damage. A stable equilibrium cell colony was established and irradiation 

simulated from 0 to 2.0 Gy in 0.1 Gy intervals. Cell survival was defined to be 

the mean fractional population surviving inside the field 612 h post-irradiation. 

Results: Simulated cell survival reached a local minimum as a function of 

dose at 0.3 Gy. Between 0.3 and 0.5 Gy the slope of the survival curve 

was positive, showing the radio-protective effect of G2 arrest. Above 0.5 Gy 

cell survival dropped with increasing dose following a conventional linearquadratic 

function. 

Conclusions: A 2D Monte Carlo model of normal epithelial cells has been 

developed which includes simple cell cycling, motility, radiation-induced G1 

and G2 arrest, apoptosis and mitotic catastrophe. The dose-response behaviour 

exhibited by the model is in quantitative agreement with published 

accounts of low-dose hyper-radiosensitivity, adding further credence to the 

reported association between this effect and the radio-response of G2-phase 

cells. 

1473 poster 


S 469 

RADIATION-INDUCED THYROID STUNNING - DIFFERENTIAL 

EFFECTS OF I-123, I-131, TM-99M AND AT-211 

C. Lundh 1 , U. Lindencrona 1 , P. Postgård 1 , T. Carlsson 2 , M. Nilsson 2 , E. 

Forssell-Aronsson 1 

1 

GÖTEBORG UNIVERSITY, SAHLGRENSKA UNIVERSITY HOSPITAL, Radiation 

Physics, Gothenburg, Sweden 

2 


of Medical Biochemistry and Cell Biology, Gothenburg, Sweden 

Purpose: Recent clinical and experimental data demonstrate that thyroid 

stunning is caused by previous irradiation, and may influence the efficacy 

of 131 I radiation therapy of thyroid cancer. To avoid stunning many clinics 

have exchanged 131 I to 123 I for pre-therapeutic diagnostic imaging and doseplanning. 

99m Tc, 211 At, 123 I and 131 I are all taken up by the thyroid via NIS, 

but have different decay properties. The main part of the absorbed dose is 

deposited by particles, but the type of particle, its energy and yield differ considerably. 

For example, alpha-particles and Auger electrons, characterized by 

high linear energy transfer (LET) and relative biological effectiveness (RBE), 

are predominantly emitted by 211 At and 123 I, respectively. This makes these 

radionuclides of interest to compare for evaluation of which type of radiation 

is more prone to induce stunning. 

Materials: TSH-stimulated thyroid cell monolayers were exposed to 0.5 Gy by 

123 I, 131 I, 99m Tc or 211 At in the culture medium for 6 h, or to various absorbed 

doses from 123 I or 131 I for 48 h. The iodide transport capacity was evaluated 

at different points in time after end of irradiation. In addition, the NIS mRNA 

expression was analysed using qRT-PCR. 

Results: Iodide transport and NIS mRNA expression were reduced by all 

radionuclides. At the same absorbed dose 211 At gave the strongest reduction 

of iodide transport, followed by 123 I and 99m Tc (equally potent), while 131 I was 

least effective. The onset of NIS down-regulation was rapid (


stander induced cell death. Key parameters in the bystander response are 

signal production, signal transport/diffusion and response to the signal. Differences 

between in vivo and in vitro cell response could be explained by 

differences in the transport/diffusion parameter.This work was supported by 

a research project grant from the NSW Cancer Council. 

1475 poster 

SHIFT OF PATIENTS’ METABOLISM TO ANAEROBIC PATHWAYS 

AFTER AMIFOSTINE ADMINISTRATION. 

C. Zois 1 , S. Tokmakidis 2 , P. Tsoutsou 1 , M. Koukourakis 1 

1 UNIVERSITRY GENERAL HOSPITAL OF ALEXANDROUPOLIS, Radiation 

Oncology, Alexandroupolis, Greece 

2 DEMOCRITUS UNIVERSITY OF THRACE, Physical Education and Sports 

Science, Komotini, Greece 

Purpose: Amifostine is a cytoprotective agent used in radiotherapy. Its active 

metabolites enter the cells and protect against free radical - induced DNA 

damage, accelerating also the DNA repair rate. We investigated the effects 

of amifostine on the basal metabolic rate (BMR) of patients (pts) with breast 

cancer. 

Materials: The oxygen (O2) consumption and carbon dioxide (CO2) production 

was assessed in 20 pts with breast cancer using the indirect calorimetric 

canopy metabolic test. Patients were asked to rest in the supine position 

for approximately 20 minutes (min) in an isolated room connected with the 

canopy system. The criterion for starting BMR was 15 min of steady state and 

BMR was performed for 50 min. Twenty five min after a steady state, recording 

patients received either subcutaneously 500mg of amifostine in 2.5ml water 

for injection (Winj) (10 pts) or Winj alone (10 pts; controls). The difference 

of oxygen consumption (dVO2) and of CO2 production (dVCO2) between the 

two halfs of recording was calculated for each patient. 

Results: The oxygen consumption was significantly reduced after the administration 

of amifostine (median dVO2 0.1±0.04 in pts receiving amfiostine vs. 

-0.10±0.02 in controls; p=0.04). The production of CO2 was also reduced 

(median dVCO2 0.13±0.03 in pts receiving amfiostine vs 0.01±0.04 in controls; 

p=0.03). 

Conclusions: Amifostine reduces the ability of normal tissues to consume 

oxygen, while at the same time the production of CO2 is reduced. An anaerobic 

shift of normal tissue glycolysis with a parallel down-regulation of the 

Crebs’ cycle is suggested. This effect may explain the side-effects of nausea 

and malaise often noted in patients receiving amifostine. Whether this normal 

tissue anaerobic shift is a pathway that contributes to cytoprotection requires 

further investigation. 

1476 poster 

THE PHYSICAL BACKGROUND AND CONSEQUENCES OF THE 

LEE-RIEGER-BARTHA MODEL FROM THE VIEWPOINT OF RADIO- 

THERAPY 

K. Baricza 1 , E. Lengyel 2 , J. Tímár 3 


2 RBH CONSULTING LTD, Budapest, Hungary 

3 NATIONAL INSTITUTE OF ONCOLOGY, Tumor Progression, Budapest, 

Hungary 

Purpose: A flow correlated bond percolation model was developed to describe 

the transition of vascular network in growing tumors [1]. Beyond reviewing 

the model our purpose is to delineate its physical background focusing 

mainly on percolation theory and to discuss the consequences to the morphology 

of the vascular network and the oxygen level affected radio-sensitivity 

of tumor cells in case of photon beam therapy. 

Materials: The vascular network of the tumors is represented by a 3D graph. 

While this graph in [1] was regular for the computational simulation, this is not 

a requirement in present study, but the graph is assumed to be characterized 

by an average coordination number z. Let p be the probability that an edge 

of a 3D graph correspond to a microvessel in the vascular network. Such 

edges/vessels form clusters of different size. If p exceeds a critical value pc 

called percolation threshold, an infinite cluster occurs. The model in [1] p is 

not constant, but it varies in the different regions of the tumour, characterized 

by their microvessel density (MVD). MVD is proportional to p, while z is equal 

to the average number of microvessels meeting at a junction in a region, 

where MVD reaches its possible maximum. An empirical method based on 

z is developed for approximate estimation of pc-s in 3D. The distribution and 

role of finite clusters is studied regarding the phenomena during growth and 

vascular transitions of the tumors. 

Results: Bond pc-s of 3D lattices can be estimated approximately as 

2.72/(2z-1). The likely deviation from the exact value is less than 1%. Finite 

clusters are formed due to the evolution of new blood vessels near the 

tumors, or occur from the infinite clusters via collapse of vessels inside the 

tumor, causing local deviances in oxygen concentration. 

Conclusions: If the ratio of MVD of a shell to the maximum MVD in the 

tumour is less than the pc value estimated on the basis of z, the region surrounded 

by this shell is almost surely excluded from the blood circulation. 

Radio-sensitivity of tumor cells trends to decrease from the surface towards 

the centre of the tumor, but small regions can be more sensitive than their 

close vicinity. Reference [1] D.-S. Lee, H. Rieger, K. Bartha: Flow Correlated 

Percolation during Vascular Remodeling in Growing Tumors, 2006 Phys. Rev. 

Lett. 96, 058104-1-058104-4 

1477 poster 

THE PREVENTIVE EFFECT OF N-ACETYLCYSTEINE ON 

RADIATION-INDUCED OXIDATIVE DAMAGE IN A RAT MODEL 

S. Kilciksiz 1 , C. Demirel 2 , N. Erdal 3 , S. Gurgul 3 , L. Tamer 4 , L. Ayaz 4 , Y. 

Ors 1 

1 

FACULTY OF MEDICINE, GAZIANTEP UNIVERSITY, Department of Radiation 

Oncology, Gaziantep, Turkey 

2 

FACULTY OF MEDICINE, GAZIANTEP UNIVERSITY, Department of Biophysics, 

Gaziantep, Turkey 

3 

FACULTY OF MEDICINE, MERSIN UNIVERSITY, Department of Biophysics, 

Mersin, Turkey 

4 

FACULTY OF MEDICINE, MERSIN UNIVERSITY, Department of Biochemistry 

, Mersin, Turkey 

Purpose: Our study aimed at investigating potential radioprotective effects 

of N-acetylcysteine (NAC) comparing its biochemical effects with that of WR- 

2721, as a representative of clinically used radioprotector, in preventing oxidative 

damage caused by gamma irradiation (single dose, 6 Gy) in normal 

rat tissue. 

Materials: The rats (n=40) were divided randomly and equally into four 

groups: Control (C, received 2.2 ml saline), Radiation (R, received irradiation 

and 2.2 ml saline), R+NAC (received irradiation and 1000 mg/kg NAC) and 

R+WR-2721 (received irradiation and 200 mg/kg WR-2721) rats. Liver tissues 

and blood samples were harvested and utilized for reduced glutathione 

(GSH), malondialdehyde (MDA) and myeloperoxidase (MPO) detections. 

Results: Serum and tissue GSH levels of R rats decreased compared to 

those of other groups (P0.05). We found a significant difference in 

tissue MDA levels between R and C rats (P

Purpose: The 92-110 kDa transmembrane glycoprotein CD133 (human 

Prominin-1) has recently been identified and discussed as potential cell surface 

marker for tumor-initiating cell subpopulations (tumor stem cells) in 

various tumor entities. The recent observation of a small CD133 positive 

(CD133 + ) tumor initiating cell population in colorectal carcinomas (CRC) that 

may only be maintained in vitro in a serum-free, 3-D environment is challenging 

and requires further examination, in particular with respect to classical 

cancer cell line models that are applied in vitro and in xenograft models 

to monitor therapeutic efficacy. Characteristics and therapeutic relevance of 

CD133 + / - subpopulations originated from cell lines are to be explored. 

Materials: Various (15) established CRC cell lines were cultured under identical 

routine conditions in monolayer and 3-D liquid overlay spheroid culture. 

CD133 expression was assessed by fluorescence microscopy and flow cytometry 

following multicolor staining and in whole cell protein extracts by WB 

(Western Blotting). A protocol to separate distinct CD133 subpopulations by 

FACS (fluorescence activated cell sorting) was established. Sorted cell populations 

were analyzed for colony formation after single dose irradiation and 

for spheroid formation capacity. 

Results: CD133 is expressed by some but not all CRC cell lines. Three categories 

could be defined: CD133 + , CD133 - and cell lines with two distinct subpopulations 

(mixed). Mixed cell lines were genetically analyzed to confirm cell 

line origin. Then, CD133 + and CD133 - subpopulations of one cell line were 

isolated. WB analyses verified that the CD133 - subpopulation does not express 

intracellular CD133 protein. Both, CD133 + and CD133 - subpopulations 

aggregated and showed similar spheroid volume growth kinetics. Also, preliminary 

colony formation assays did not indicate enhanced radioresistance 

of the CD133 + subpopulation. 

Conclusions: Some classical CRC cell lines contain CD133 + and CD133 - 

subpopulations under standard culture conditions. Subpopulations can be 

isolated for further in vitro and in vivo characterization. First data indicate 

that CD133 + and CD133 - subpopulations may not differ in radiosensitivity 

and spheroid formation capacity. However, extended studies are required to 

verify these results and to also validate cell survival and CD133 expression 

pattern in a pathophysiologic milieu, and the tumor-initiating potential of the 

cell populations in vivo. 

1479 poster 

[18F]FDG-UPTAKE IN HYPOXIC AREAS AFTER SINGLE DOSE 

IRRADIATION IN FADU HSCC XENOGRAFTS 

K. Brüchner 1 , F. Hofheinz 2 , R. Bergmann 3 , A. Yaromina 1 , F. Hessel 4 , J. 

van den Hoff 5 , M. Baumann 6 , B. Beuthien-Baumann 7 

1 

MEDIZINISCHE FAKULTÄT CARL GUSTAV CARUS TECHNISCHE UNIVERSITÄT 

DRESDEN, Klinik und Poliklinik für Strahlentherapie und Radioonkologie, 

OncoRay, Dresden, Germany 

2 

ABX ADVANCED BIOCHEMICAL COMPOUNDS, Radeberg, Germany 

3 

FORSCHUNGSZENTRUM DRESDEN-ROSSENDORF, Institut für Radiopharmazie, 


4 

UNIVERSITÄTSKLINIKUM TECHNISCHE UNIVERSITÄT DRESDEN, Klinik und 

Poliklinik für Strahlentherapie und Radioonkologie, Dresden, Germany 

5 

FORSCHUNGSZENTRUM DRESDEN-ROSSENDORF, Abteilung Positronen- 

Emissions-Tomographie, Dresden, Germany 

6 

UNIVERSITÄTSKLINIKUM TECHNISCHE UNIVERSITÄT DRESDEN, Klinik und 

Poliklinik für Strahlentherapie und Radioonkologie, OncoRay, Experime, 


7 

UNIVERSITÄTSKLINIKUM TECHNISCHE UNIVERSITÄT DRESDEN, Klinik für 

Nuklearmedizin, Dresden, Germany 

Purpose: Purpose: Tumours show often a high degree of heterogeneity. 

This was also demonstrated for the inter-tumoural and intra-tumoural [18F]2fluoro-2-deoxy-glucose 

([18F]FDG) uptake. We could show that [18F]FDGuptake 

in unirradiated FaDu xenografts was significantly higher in hypoxic 

tumour areas in comparison to nonhypoxic. The aim of this study was to investigate 

possible changes of [18F]FDG-uptake in relation to hypoxia after 

single dose irradiation using autoradiography and quantitative histology. 

Materials: Materials and Methods: 32 human FaDu squamous cell carcinoma 

(hSCC) in nude mice with a volume of 243.1 mm 17.4mm 

entered the study. Single dose irradiations of 25 and 35 Gy were applied using 

200kV X-rays (0.5mm Cu, ~1.2 Gy min-1). Tumours were investigated 1, 

7 or 11 days p.irr.. Mice were injected with pimonidazole (pimo) for functional 

histology. 30 min later [18F]FDG (4-11 MBq/injection) was i.v. injectected and 

60 min p.i. tumour and liver (reference tissue) were excised, frozen, and serial 

cuts of 20 µm were subjected to autoradiography. After autoradiography, the 

tumour slices were stained for pimo and scanned with a digital camera. Using 

image analysis software vital tumour, necrosis and hypoxic tumour areas 

(pimo staining) were delineated. Autoradiographic images were coregistered 

to the corresponding histology scan and tumour masks, and the [18F]FDGuptake 

was quantitated and compared to the hypoxic area. 

Results: Results: At day 1 in both dose groups [18F]FDG-uptake was higher 

in hypoxic tumour areas (3.09%ID/g±0.5 vs. 5.03±1.1 after 25 Gy and 

3.97±0.9 after 35 Gy) in comparison to unirradiated FaDu. This increase was 

more pronounced after 25 Gy than after 35 Gy. At day 7 the [18F]FDG-uptake 

in the hypoxic regions had decreased in both dose groups. A further decrease 

was seen at day 11 after irradiation with 25 Gy. In the 35 Gy group the 

[18F]FDG-uptake was stable in relation to day 7, but the size of hypoxic area 

RADIOBIOLOGY : PREDICTIVE ASSAYS/PROGNOSTIC FACTORS 

S 471 

had shrunk considerably (day 7: 0.036cm±0.03; day 11: 0.006cm±0.005). 

The difference between [18F]FDG-uptake in pimo-positive and pimo-negative 

tumour areas had declined at day 7 and day 11(25 Gy: day 1: ∆1.66; day 

7: ∆1.02; day 11: ∆0.21 / 35 Gy: day 1: ∆1.15; day 7: ∆0.55; day 11: 

∆0.51). 

Conclusions: Conclusions: The glucose consumption of hypoxic tumour regions 

in FaDu was increased at early time-points after irradiation in comparison 

to the unirradiated tumours. Over the time after irradiation the decreasing 

glucose uptake was caused by cell damage, decreasing cell metabolism and 

lower cell density.This work was supported by the 6th framework EU-project 

"BioCare", proposal # 505785. 

Radiobiology : Predictive assays/Prognostic 

factors 

1480 poster 

COMPARISON OF PREDICTED AND CLINICAL RESPONSE TO 

RADIOTHERAPY IN HEAD AND NECK PATIENTS 

M. Hedman 1 , T. Björk-Eriksson 2 , C. West 3 , C. Mercke 1 , P. Hesselius 4 , 

O. Brodin 1 

1 

KAROLINSKA UNIVERSITY HOSPITAL, Clinical Oncology, Stockholm, 

Sweden 

2 


3 

UNIVERSITY OF MANCHESTER, CHRISTIE HOSPITAL NHS TRUST, 

Academic Radiation Oncology, Manchester, United Kingdom 

4 

UPPSALA UNIVERSITY, Statistical Institution, Uppsala, Sweden 

Purpose: A model to predict clinical outcome after radiation therapy would 

be a valuable aid in the effort of developing more tailored treatment regimes 

for different patients. In this work we evaluate a model using the following 

individual radiobiology parameters: intrinsic radiosensitivity, proliferation and 

number of clonogenic cells. The theory behind this work was that individual 

tumour parameters can predict treatment outcome and will increase the 

reliability of such a model compared with average population derived data. 

Materials: Fourty-six patients with head and neck tumours were analyzed 

and a majority of these received both external radiotherapy and brachytherapy. 

18 patients only received external beam treatment and statistical evaluation 

was made on this subgroup 

Results: Four patients had a >95% calculated probability of cure and none of 

these had a local recurrence resulting in a negative predictive value of 100% 

(67% for population derived data). The sensitivity of the test in predicting 

local recurrence was 75% (vs.38%). When patients with >95% and

S 472 RADIOBIOLOGY : PREDICTIVE ASSAYS/PROGNOSTIC FACTORS 

ual differences in the radiation response are observable, but these differences 

are not significant. As expected, cytogenetic damage increases during the radiotherapy 

course. One year after the treatment the aberration yield is only 

slightly lower than at the end of therapy. The data obtained so far show no difference 

between patients treated with or without C-ion boost. Although complex 

aberrations are discussed as a fingerprint of high LET exposure, their 

numbers are low in lymphocytes of patients receiving a C-ion boost. When 

these yields are compared to the data generated for the patients treated solely 

with photon IMRT, again no significant differences is observed. In contrast, in 

lymphocytes exposed in vitro to 2 Gy C-ions (LET=175 keV/Ym) the yield of 

complex aberrations is up to five times higher than in cells exposed to 2 Gy 

X-rays. 

Conclusions: The data obtained for prostate cancer patients indicate that 

additional application of C-ion boost do not produce more cytogenetic damage 

in peripheral blood lymphocytes than sparsely ionizing radiation alone. 

So far we have no indication of an enhanced RBE of heavy particles for the 

induction of cytogenetic changes in normal tissue in the short course of particle 

therapy. Supported by BMBF (Bonn, Germany) under contract 02S8497. 

1482 poster 

EARLY TRANSCRIPTOMIC CHANGES AS A PREDICTIVE FACTOR 

OF THE EFFICACY OF PREOPERATIVE RADIOTHERAPY OF 

RECTAL CANCER: A FEASIBILITY STUDY. 

S. Supiot 1 , W. Gouraud 1 , L. Campion 1 , P. Jezequel 1 , S. Minvielle 1 , 

B. Buecher 1 , J. Charrier 1 , M. F. Heymann 1 , M. A. Mahé 1 , E. Rio 1 , M. 

Cherel 1 

1 CENTRE RENÉ GAUDUCHEAU, Radiation Oncology, Saint-Herblain, France 

Purpose: Despite intense research, no biomarker can predict tumor response 

to preoperative radiotherapy for rectal cancer. Micro-arrays profiling 

offers the possibility to explore the expression of large amounts of genes. 

We hypothesized that transcriptomic changes occurring during the first treatments 

of radiotherapy may predict the final pathological response of rectal 

tumors to preoperative radiotherapy. We conducted a pilot study to test the 

safety and feasibility of rectal tumor biopsies before and during radiotherapy, 

and assessed for gene expression changes. 

Materials: Six patients presenting a locally advanced rectal cancer (T>T2, 

N0/Nx, M0) eligible for preoperative radiotherapy (45 Gy in 25 fractions) were 

selected. Exclusion criterias were : anti-coagulant therapy, cardiac valvular 

disease, pelvic pain due to prior biopsies. Six tumor and 3 normal tissues 

biopsies were taken before and during radiotherapy, after a dose of 7.2 Gy. 

Patients were assessed for toxicity of the biopsy process. Tumor or normal tissue 

purity was assessed by a pathologist prior to RNA extraction. After RNA 

amplification, biopsies were analysed with 54K HG-U133APlus2.0 Affymetrix 

expression micro-arrays. Data were normalized according to MAS5 algorithm. 

A gene expression ratio was calculated as: (gene expression during 

radiotherapy gene expression before radiotherapy) / gene expression before 

radiotherapy. Were selected genes that showed a ratio higher than + 0.5 or 

lower than -0.5 in all 6 patients. 

Results: Biopsies were taken at a median time of 1.0 hours following 

irradiation (0:27-2:12). No toxicity provoked by the biopsies was reported. 

Mean RNA content was 23 µg/biopsy (14-37) before radiotherapy 

and 22.7 µg/biopsy (12-35) during radiotherapy. Micro-arrays analysis 

showed that preoperative radiotherapy of rectal cancer significantly upregulated 

205 genes and downregulated 58 genes, including genes involved in 

lipid metabolic process, intracellular signaling cascade, regulation of transcription, 

transport, regulation of cell growth, and signal transduction. A complete 

statistical analysis is being processed. 

Conclusions: Rectal cancer biopsies are feasible during radiotherapy without 

increased toxicity. This pilot study shows that micro-arrays can efficiently 

assess early transcriptomic changes during radiotherapy. This may help 

better understand tumor radioresistance mechanisms and determine new 

biomarkers of the response of rectal cancer to preoperative radiotherapy 

1483 poster 

EFFECTS OF SENSITIVE TO APOPTOSIS GENE (SAG) AND P73 

GENES ON RADIOTHERAPY AND/OR CHEMOTHERAPY 

S. Özden 1 , O. Orun 2 , H. Ozyurt 1 , Z. Ozgen 1 , N. Ozseker 1 , M. Oncel 3 , 

B. Kan 2 

1 

DR. LÜTFI KÝRDAR KARTAL EGITIM VE ARASTÝRMA HASTANESI, Radiation 

Oncology, Ýstanbul, Turkey 

2 

MARMARA UNIVERSITY, FACULTY OF MEDICINE, Biophysics, Ýstanbul, 

Turkey 

3 

DR. LÜTFI KÝRDAR KARTAL EGITIM VE ARASTÝRMA HASTANESI, General 

Surgery, Ýstanbul, Turkey 

Purpose: Radiotherapy and chemotherapy can both induce apoptosis as 

one of their effect mechanisms. Radiotherapy causes the production of reactive 

oxygen species which induce apoptotic pathways indirectly. Sensitive 

to apoptosis gene (SAG) protects cells from apoptosis induced by reactive 

oxygen species. p73 protein, a member of p53 family, also plays an impor- 

tant role in apoptosis. Overexpression of p73, has been shown to increase 

radiosensitivity via apoptosis in cervix cancer. 

Materials: In this study, ten patients with rectum cancer to whom neoadjuvant 

chemoradiotherapy was applied, were examined for SAG, p73, BclxL 

and Bak expression before the radio/chemotherapeutic treatment started. 

Expression levels were compared with the histo-pathologic results obtained 

after the surgery. 

Results: Bcl-xL was found to be increased, in contrast to Bak expression 

which decreased in all of the patients. The increase in SAG expression in 

90% of the patients (n: 9/10) suggested that anti-apoptotic pathways were 

dominant in our tumor series. One patient who had a decreased SAG expression 

level showed a nearly complete response to chemo-radiotherapy. In 

view of this, we propose that more than one anti-apoptotic pathway acting simultaneously 

may have a stronger effect on the outcome. In our study out of 

10 patients, 4 were recorded as nonresponsive (SAG levels were elevated); 

3, as moderate (SAG levels were elevated); 2, as nearly fully responsive (one 

increase, one decrease in SAG levels) and 1 as fully responsive (increased 

SAG level). Half of the six patients who had decreased level of p73 expression 

showed good and complete response. 

Conclusions: In conclusion, our preliminary results suggest that SAG and 

p73 genes may have high prognostic and predictive values in rectum cancer. 

Studies with larger population of patients which also include assesment of 

apoptosis levels in the same tissues are currently in progress. 

1484 poster 

IDENTIFICATION OF KEY REGULATOR GENES LINKED TO RA- 

DIORESISTANCE IN HNSCC BY BIOINFORMATIC PROCESSING OF 

TRANSCRIPT DATA 

F. Jerhammar 1 , R. Ceder 2 , R. C. Grafstrom 2 , K. Roberg 1 

1 

LINKÖPING UNIVERSITY HOSPITAL, Division of Otorhinolaryngology, 

Linköping, Sweden 

2 

KAROLINSKA INSTITUTE, Institute of Environmental Medicine, Stockholm, 

Sweden 

Purpose: Identification of molecular markers correlating with radioresistance 

by application of bioinformatic tools for analysis of large transcript data sets. 

Materials: Five head and neck squamous cell carcinoma (HNSCC) cell lines 

with varying radiosensitivity were selected for microarray analysis which was 

performed using the Affymetrix Human Genome U133 Plus 2.0 Chip. Two 

cell lines showed high resistance to radiation (named H1 and H2), two cell 

lines showed an intermediate resistance (named I1 and I2) whereas one cell 

line was sensitive and therefore viewed as control (named C). The I and H 

cell lines were compared to the C cell line respectively, and transcripts with 

a fold-change value of 2.8 (p

a single cell type to a test dose of radiation in vitro as surrogate of normal 

tissue radiation response have been extensively investigated. Results on the 

predictive value of FCBA have been inconsistent and this lack of progress, 

plus the advent of newer technologies, has led to a decline in interest in the 

use of such assays as predictive tests. The failure of FCBA to deliver on 

their early promise may, in part, be due to poor study design. Issues concerning 

study design and reporting are addressed by the REMARK criteria 

for assessing studies of prognostic factors in cancer. We ask whether there is 

sufficient evidence available to dismiss altogether the utility of FCBA in predictive 

testing of normal tissue radiosensitivity, or have problems with study 

design; statistical analyses and reporting masked their potential value? 

Materials: We performed a systematic review of the literature. Studies published 

between 1966-2008 directly linking the result of functional cell based 

assay with clinical data on normal tissue toxicity were identified. Each was assessed 

according to the REMARK reporting criteria with reference to reporting 

of laboratory quality control, correction for potential confounding factors 

and use of appropriate statistical analysis. Where possible individual patient 

data was extracted and ROC analysis performed to calculate cut-offs, sensitivity, 

specificity and likelihood ratios as measures of assay performance. 

Results: We identified 54 publications that fulfilled our eligibility criteria for 

inclusion. The majority were small retrospective case-control studies.59% reported 

that the assay under investigation could detect differences between 

individuals suffering from different severities of normal tissue toxicity Only 2 

studies used ROC analysis and reported assay sensitivity and sensitivity and 

predictive value. Reporting of the existence of, and adjustment for, potential 

confounding factors was inconsistent. No study completely fulfilled the RE- 

MARK reporting criteria. Our ROC-based re-analysis of extracted individual 

patient data confirms that some FCBA do have limited discriminatory ability. 

Conclusions: Difficulties in study design and controlling for confounding factors 

may have masked the potential clinical utility of FCBA in the predictive 

testing of normal tissue radiosensitivity. Future studies should be designed 

with this in mind and reported according to standardised criteria applicable to 

prognostic assay research. 

1486 poster 

MEASUREMENT OF GAMMA-H2AX IN BLOOD MONONUCLEAR 

CELLS AFTER RADIOTHERAPY 

O. Hammarsten 1 , R. Hultborn 2 , A. Muslimovic 1 , A. Jellvart 2 

1 SAHLGRENS UNIVERSITY HOSPITAL, Department of clinical chemistry and 

transfusion medicine, Gothenburg, Sweden 

2 SAHLGRENS UNIVERSITY HOSPITAL, Department of Oncology, Gothen- 

burg, Sweden 

Purpose: Phosphorylation of histone protein H2AX on serine 139 (gamma- 

H2AX) occurs at sites flanking DNA double-strand breaks (DSBs) and can 

provide a measure of the number of DSBs within a cell. Gamma-H2AX measurements 

in mononuclear cells can therefore serve as a way to measure the 

biological response to the delivered dose during radiotherapy. 

Materials: We have used a flow cytometry-based method optimized to measure 

gamma-H2AX in non-fixed mononuclear blood to follow gamma-H2AX 

expressing cells in patient blood after radiotherapy. 

Results: In a pilot study we have analyzed blood samples from patients receiving 

5 Gy of gamma irradiation to the pelvic area. As a control, we also 

analyzed the gamma-H2AX signal in in vitro irradiated mononuclear cells from 

the same patients All mononuclear cells from the irradiated patients showed 

a slight increase of the gamma-H2AX signal after irradiation, corresponding 

to a dose of 0.3 - 0.5 Gy. The gamma-H2AX signal in these cells will likely be 

below the detection limit if the more conventional radiation dose of 2 Gy were 

used and will likely vary depending on the blood flow through the irradiated 

volume. However, we also observed a small fraction of mononuclear cells that 

apparently have received the full 5 Gy of irradiation since their gamma-H2AX 

signal matched the signal observed in the in vitro irradiated mononuclear 

cells. These mononuclear cells were likely trapped in the micro circulation 

in the irradiated area during the two minutes of irradiation and then released 

into the systemic circulation. These high gamma-H2AX signal cells that we 

now call "sentinel cells" accumulate after irradiation and constitute over to 10 

% of all mononuclear cells one hour after the irradiation. Measurement of the 

relative amount of sentinel cells, the interindividual signal and kinetics in the 

circulation after different forms of radiotherapy will be presented. 

Conclusions: Measurement of sentinel cells by flow cytometry could be a 

way to quantify the DNA-damage response during radiotherapy. 

RADIOBIOLOGY : PREDICTIVE ASSAYS/PROGNOSTIC FACTORS 

1487 poster 

S 473 

NOVEL APPLICATION OF LOW-FREQUENCY ULTRASOUND 

TO MONITOR TUMOR RESPONSE IN PROSTATE CANCER 

XENOGRAFT 

B. Banihashemi 1 , L. Justin 1 , A. Giles 1 , P. Naum 1 , M. Kolios 2 , G. 

Czarnota 1 

1 SUNNYBROOK HEALTH SCIENCES CENTRE, Departments of Radiation 

Oncology, and Imaging Research, Toronto, Canada 

2 RYERSON UNIVERSITY, Department of Physics and Computer Science, 

Toronto, Canada 

Purpose: High-frequency ultrasound has been used in the past to detect 

apoptosis. It has limited penetration due to attenuation. We have previously 

demonstrated that deeper penetrating diagnostic conventional-frequency ultrasound 

can monitor apoptosis with AML-cell samples in vitro. In this study, 

we evaluated the first-time use of conventional-frequency ultrasound to assess 

tumor responses to radiation in vivo. 

Materials: Malignant PC3 prostate tumors were treated with a 2 or 8 Gy single 

fraction of radiation in the presence or absence of endothelial-cell perturbing 

radiosenstizers (750 kHz activated microbubbles). Tumors were examined 

by a 10MHz US before and 24h after treatment. Images and backscattered 

spectroscopic data were acquired. Data were analyzed and compared to 

standard histopathological markers of apoptotic cell death (including H&E and 

TUNEL staining). 

Results: At 24h after radiation, we observed a significant increase in apoptosis 

histologically with induced radiosensitization. Spectroscopic analysis of 

ultrasound data indicated increases in spectral slope and mid-band fit (MBF). 

The MBF increased from -50+/-1 dB in the untreated tumors to -47+/- 1 dB 

at 24h after exposure to RT alone. In the presence radiosensitization, MBF 

increase by 5 +/- 1 and 8 +/- 1 dB with 2 and 8Gy radiation doses, respectively. 

Such samples upon analysis demonstrated 40% and 54% apoptosis 

in histopathology analysis whereas at 24h after exposure to radiation alone, 

only 2-4% apoptosis was detected. The spectral slope in LFUS backscatter 

was 1.8 dB/MHz prior to treatment that changed to 0.8 and 0.7 dB/MHz 

with 2 and 8Gy radiation in the presence of radiation sensitizers respectively. 

Higher sensitization levels caused more apoptosis in the tumors that could be 

detected with ultrasound. 

Conclusions: In conclusion for the first time we demonstrate here, that 

conventional-frequency ultrasound can detect real-time tumour responses. 

Assessing such responses early in the course of cancer treatment may provide 

an opportunity to customize treatments accordingly for individual patients. 

1488 poster 

P53 CODON 72 PREDICTS INDIVIDUAL RADIOSENSITIVITY OF 

ACUTE SKIN REACTION 

U. Thunberg 1 , J. Nyman 2 , I. Hermansson 2 , M. Book 1 , K. A. Johansson 

3 , I. Turesson 4 

1 



2 



3 

GÖTEBORG UNIVERSITY, SAHLGRENSKA UNIVERSITY HOSPITAL, Gothenburg, 

Sweden 

4 

UPPSALA UNIVERSITY, Oncology, Uppsala, Sweden 

Purpose: Our aim in this study was to investigate p53 codon 72 polymorphism 

and individual radiosensitivity concerning acute effects. The tumor 

suppressor gene p53 is activated by stress, as for example DNA damage 

caused by radiation, leading to DNA repair, cell cycle arrest and induction 

of apoptosis. However, the effectiveness of the various functions of p53 depends 

on a common polymorphism codon 72 (Arg or Pro). Cells with Arg 72 

are more efficient for apoptosis compared to cells with Pro 72. In contrast 

cells with the Pro 72 genotype induce a higher level of G1. 

Materials: In patients who had received curative radiotherapy for prostate 

cancer, 3mm skin biopsies were taken regularly during the treatment period 

of 7 weeks from two lateral fields. The fractionation scedules were 5*0.45 

Gy/week and 5*1.1 Gy7 week. In 76 patients the rate of reduction of keratinocytes 

in the basal cell layer of epidermis was determined and taken as 

endpoint for individual radiosensitivity. DNA was taken from 117 unirradiated 

control biopsies to determine codon 72 polymorphism. 

Results: Analysis of the p53 codon 72 polymorphism in the prostate patients 

showed that 65 (56%) individuals were Arg/Arg, 42 (36%) were Arg/Pro and 

10 (8%) were Pro/Pro. The dose response for keratinocytes and 0.45 Gy 

is exponential. Therefore the individual radiosensitivity is determined by the 

slope for each patient. When variants for p53 codon 72 were correlated to 

the keratinocyte response we found that patients with Arg/Arg had significant 

less reduction rate after daily fractions of 0.45 Gy compared to patients with 

Arg/Pro or Pro/Pro (P=0.007). The Arg/Arg patients had also less reduction 

rate of keratinocyte after daily fractions 0.45 Gy compared to patients with 

Arg/Pro patients alone (P=0.01). There was no significant difference of reduction 

rate of keratinocyte when Pro/Pro patients were compared to Arg/Pro

S 474 RADIOBIOLOGY : PREDICTIVE ASSAYS/PROGNOSTIC FACTORS 

patients (P=0.9). The dose-modifying factor for the Pro 72 heterozygotes or 

homozygotes versus Arg 72 homozygotes was 0.8. This was confirmed by 

the outcome of daily fractions of 1.1 Gy given to the same patient cohort. 

Conclusions: The p53 polymorphism codon 72 does explain part of the individual 

radiosensitivity of the skin epithel. This will have implications for prescribing 

the individual dose of radiotherapy. 

1489 poster 

POTENTIAL PREDICTIVE VALUE OF "RADIOSENSITIVITY CLASSI- 

FIER" IN PROSTATE CANCER 

E. Malusecka 1 , A. Fiszer-Kierzkowska 1 , M. Jarzab 2 , M. Kowalska 3 , 

M. Gawkowska-Suwinska 4 , K. Wolanska 5 , A. Zborek 5 , J. Rembak- 

Szynkiewicz 6 , B. Bobek-Billewicz 6 , A. Zajusz 4 , Z. Krawczyk 5 , B. 

Maciejewski 1 


OF ONCOLOGY, Department of Radiotherapy, Gliwice, Poland 


OF ONCOLOGY, Department of Clinical Oncology, Gliwice, Poland 


OF ONCOLOGY, Department of Nuclear Medicine and Endocrinology, 



OF ONCOLOGY, II Department of Radiotherapy, Gliwice, Poland 


OF ONCOLOGY, Department of Tumor Biology, Gliwice, Poland 


OF ONCOLOGY, Department of Radiodiagnostics, Gliwice, Poland 

Purpose: Prediction of tumor response to radiation therapy is currently main 

goal of radiobiology. High-throughput microarray technology offers possibility 

to study thousands of genes to subsequently acquire set of genes which expression 

would be useful in predicting response to treatment. Torres-Roca et 

al., (Cancer Res., 2005) performed in silico analysis of radiosensitivity of 35 

tumor cell lines and based on gene expression profiles identified "radiosensitivity 

classifier". 

Materials: The aim of our study was to characterize in vivo expression of 

genes of this classifier: R5PIA (ribose 5-phosphate isomerase A), RbAp48 

(retinoblastoma binding protein 4), RGS19 (G-protein signaling regulator 19) 

and evaluate its predictive value. Expression level of R5PIA, RbAp48 and 

RGS19 genes was determined in quantitative RT-PCR method. Protein expression 

pattern was determined by immunohistochemistry. 

Results: We found no statistical differences in median expression level between 

cancer and hyperplastic prostate tissue for R5PIA and RbAp48 genes. 

Expression level of RGS19 was statistically lower in prostate cancer than in 

hyperplasia (p

eceived a median dose of 40 Gy (range 34,5 - 54 Gy), while Cranial Posterior 

Fussa (CPF) received a median dose of 55 Gy (range 50,4 55,8 Gy). 

One patient was unfit for CSI because of clinical conditions and received only 

30,6 Gy on WB and 55,8 Gy on CPF. Median follow-up period was 73 months 

(range 26 182). After 2 months, we observed a CR in 11 patients (92%) and 

a PR in one patient (8%).Only one acute haematological toxicity (G3 RTOG 

score) and no late neurological toxicities were observed. Median OS was 67 

months, with a 10-years LC and DFS rate of 83%. 9/12 pts. are disease free 

survivors. 2/12 patients died for local and spinal progression after 13 and 28 

months, respectively. One patient died for other causes. P53, C-ERB-B2, 

MIB1 AND G-FAP were immunohistochemically tested 9/12 samples in order 

to investigate a possible prognostic role. Beta and gamma catenine, considered 

positive prognostic factors, were iperexpressed in all samples. P53, 

Mib-1 and c-Erb-B2, considered negative prognostic factors in MB, were not 

expressed at all. G-FAP showed an increased expression in 4/9 samples. 

Conclusions: We confirm efficacy of RT in achieving longterm LC and OS in 

adult MB. We cannot give a definitive conclusion on the prognostic meaning 

of examined biological features, but our data seem to confirm the literature. 

1493 poster 

PROTEINS AND SNPS INVOLVED IN GROWTH AND CELL DEATH 

AFFECTING CISPLATIN SENSITIVITY IN HEAD AND NECK CANCER 

CELL LINES 

K. Roberg 1 , A. Jedlinski 1 , L. Farnebo 1 , A. Ansell 1 

1 UNIVERSITY HOSPITAL, Department of Otorhinolaryngology, Linköping, 

Sweden 

Purpose: Studies have demonstrated that cisplatin based chemoradiation 

have benefit over radiotherapy alone in advanced head and neck squamous 

cell carcinoma (HNSCC). However, the addition of cisplatin does not affect 

the outcome of treatment in all patients. Therefore, the present study was undertaken 

to evaluate the possibility of using a panel of proteins and/or single 

nucleotide polymorphisms (SNPs) involved in apoptosis and/or growth control 

as predictive markers for cisplatin sensitivity. 

Materials: Cisplatin sensitivity was determined in 40 HNSCC cell lines using 

a colony-forming assay. These cell lines intrinsic cisplatin sensitivity (ICS) 

were set to values between 0 and 1. The cloning efficiency (CE) of untreated 

cells (control) was set to 1 (=100%), and the CE of treated cells was expressed 

as a ratio of the control value (0 1). SNPs were analyzed in the 

genes of p53, mdm2, FGFR4, XPC, XPD, XRCC1 and XRCC3. Seven proteins 

e.g. Bcl-2, Bcl-XL, Bax, survivin, COX-2, Hsp70 and EGFR were investigated 

in above mentioned cell lines and in normal oral keratinocytes (NOK). 

Each protein was quantified using ELISA. 

Results: EGFR was the only protein that alone has a significant correlation 

to ICS when using Pearsons correlation test and protein values from ELISA 

(R=0.337, p=0.033). To test if combinations of these proteins could have 

significant correlation to ICS, the protein expression was classified into four 

groups (0-3 points; no, small, middle or large changes of the protein expression 

compare to NOK) and different combinations were statistically analyzed. 

We found that the combination of EGFR, Hsp70, Bax and Bcl-2 gave the best 

correlation to ICS, R=0.604 and P=0.05). When looking at patients in the RT group, 

those with GC/GC genotype, low p53 and low survivin compared to the rest 

of the patients, had a significantly better survival. This was not seen in the 

non-RT group. 

Conclusions: In preoperatively radiated samples there seems to be a connection 

between the p73 genotype and expression of the predictive factors 

p53 and survivin. The GC/GC genotype may be more favourable in rectal 

cancer patients treated with preoperative RT. 

1496 poster 

SYSTEMATIC REVIEW AND SYNTHESIS: VOLUME AND PROGNO- 

SIS IN RADIOTHERAPY OF HEAD AND NECK CANCER 

J. P. Voroney 1 , S. Rauth 2 , S. Keller 1 , W. MacKillop 1 

1 QUEEN’S UNIVERSITY CANCER RESEARCH INSTITUTE, Division of Cancer 

Care and Epidemiology, Second floor, Kingston, Ontario, Canada 

2 PRINCESS MARGARET HOSPITAL, Department of Radiation Oncology, 

Toronto, Canada

S 476 RADIOBIOLOGY : RADIOSENSITISERS 

Purpose: To systematically review head and neck cancer literature regarding 

the prognostic significance of imaging-based tumor volumes. To develop a 

tumor control model for radiotherapy outcomes whose validity spans multiple 

data sets and that can account for differences in tumor control related to 

hypoxia or imaging surrogates of radioresistance. 

Materials: A Medline search based on the terms volume, prognosis, radiotherapy 

and head and neck cancer yielded 52 studies on 3807 patients, 

providing outcomes grouped according to initial primary tumor volume, total 

tumor volume, and hypoxic/radioresistant volume. Data was abstracted 

according to types of outcome (local or locoregional control; disease-free, 

disease-specific, or overall survival) and volumetric grouping (average volume 

of controlled tumors versus tumors that fail, grouped by tumor volume in 

bins, tumor volume as a continuous variable). Weibull distribution of treatment 

failures was used to adjust local control rate when follow-up was less than 5 

years; lognormal distribution was assumed when volume distribution was incompletely 

described. Studies with similar volume groupings and outcome 

measures were analyzed together. Normalized data was graphed and fitted 

to tumor control probability (TCP) models that include hypoxia or imagingbased 

surrogates of radioresistance. 

Results: Overall, 46/52 studies (89% of patients) showed poorer prognosis 

with increasing tumor volume, although this was not always statistically 

significant in all subgroups or in multivariate analysis. In 12 studies multivariate 

analysis showed poorer prognosis associated with surrogates of radioresistance, 

which included cartilage/bone invasion on CT or MR (6 studies 

p=0.0001-0.07), Eppendorf hypoxic fraction (2 studies p=0.01-0.08) and 

perfusion abnormalities on Doppler ultrasound or contrast CT (4 studies 

p=0.002-0.07). The significant and demonstrable effect of volume, V, on local 

control is non-linear and consistent with an exponentially decreasing function 

of initial tumor volume, TCP = e -kV where the rate k depends on site: 

for oral cavity, hypopharynx and oropharynx k = 0.024 mL -1 standard error 

(SE) 0.003, 9 studies N=682; for supraglottis k = 0.16 mL -1 SE 0.03, 6 studies 

N=408; for glottis k = 0.36 mL -1 SE 0.07, 6 studies N=468. The control 

rate k is also dependent on treatment and surrogates of radioresistance. The 

prognostic effect of volume is robust- it persists in studies where additional 

radiotherapy or chemotherapy was given to patients with more advanced disease. 

Conclusions: Tumor volume provides a useful and powerful measure to determine 

patients who are at risk of local failure and would benefit from improved 

radiotherapy treatment and process. Promising studies on surrogates 

of radioresistance suggest additional imaging parameters may be significant 

for prognosis. 

1497 poster 

THE PROSTATIC VOLUME: A FACTOR TO CHOOSE THE PRE- 

SCRIPTION DOSE IN PROSTATE PERMANENT IMPLANTS WITH 

I-125 

V. Bourel 1 , M. de la Torre 2 

1 FAVALORO UNIVERSITY, Medical Physics, Buenos Aires, Argentina 

2 HOSPITAL DE CLÍNICAS, Radiotherapy, Buenos Aires, Argentina 

Purpose: To analyze the reason why the tumor control probability (TCP) in 

patients treated in our center with permanent implants is greater in smaller 

prostatic volumes although in all patients, independently of the volume, the 

same prescription dose (145 Gy) was used. 

Materials: Between November 2003 and October 2007 147 patients were 

treated with prostate permanent implants with I-125. Preplanning was performed 

in all patients with ultrasound images obtained approximately 10 days 

before the date of the implant. The selected PTV was obtained as the prostatic 

volume plus a 3mm of margin. On this PTV 145 Gy was prescribed in all 

patients without distinction of prostatic volume. The average prostatic volume 

(without margin) was 33.6 cm 3 . All treatments were carried out with loose 

seeds with an approximate activity of 0.6 mCi per seed. The radiobiological 

analysis was made based on equivalent uniform dose (EUD) calculations 

using the linear-quadratic model to calculate cell survival. The EUDs were 

obtained from DVHs. The parameters used in the linear-quadratic model for 

prostatic tissue were alpha = 0.15 Gy -1 and alpha/beta = 3.1 Gy. In previous 

works ( 2008 World Congress of Brachytherapy ) we showed that in our 

experience the prostatic volume was a determining factor for EUD calculation. 

Analyzing volumes from 30 cm 3 to 45 cm 3 we found a 18% difference in 

the EUD values between the ends, which gave like result a greater TCP for 

prostates with small volume. 

Results: A detailed dosimetric analysis showed that in bigger prostates we 

found, proportionally, greater volume with low doses (closer to prescription 

dose). This effect is not compensated with volumes with greater doses, because 

the implantation technique limits these values, in particular because 

dose limitation in urethra. As representative parameter of this effect we have 

used the difference (V100 - V150) finding a range from 28.8% to 43.4% for 

30 cm 3 to 45 cm 3 . 

Conclusions: The obtained results suggest that dose prescription in prostate 

permanent implants should be function of the prostate volume, for greater 

volumes greater dose prescription, to obtain same TCP. At least with our implantation 

technique 

1498 poster 

VALIDATION OF A KNOWLEDGE BASED APPROACH FOR DERIV- 

ING A HYPOXIA ASSOCIATED GENE SIGNATURE 

C. West 1 , S. Bhana 1 , G. Foley 1 , C. Möller-Levet 2 , H. Valentine 1 , C. Miller 

2 , A. Harris 3 , P. Price 1 

1 

UNIVERSITY OF MANCHESTER, Academic Radiation Oncology, Manchester, 


2 

PATERSON INSTITUTE FOR CANCER RESEARCH, Applied Computational 

Biology and Bioinformatics , Manchester, United Kingdom 

3 

WEATHERALL INSTITUTE OF MOLECULAR MEDICINE, Cancer Research UK 

Molecular Oncology Laboratories, Oxford, United Kingdom 

Purpose: Microarray profiling of 59 head and neck squamous cell cancers 

was previously used to derive a hypoxia-associated gene signature. A novel 

knowledge-based approach was used to obtain the 99-gene signature, the 

in vivo expression of which clustered with the expression of 10 well-known 

hypoxia-regulated genes. The median expression of the 99 genes was an 

independent prognostic factor for recurrence-free survival in an independent 

data set, out performing the original trained classifier. Of the 99 genes comprising 

the signature only 27% were previously known to be hypoxia associated. 

The aim of this work was to validate the knowledge-based approach for 

deriving the gene signature by investigating the hypoxia inducibility of several 

selected genes not previously reported to be hypoxia-regulated. 

Materials: Gene induction was investigated after 2 and 24 h hypoxia (1%) followed 

by 2 and 24 h re-oxygenation. Head and neck (CAL-27, FADU), breast 

(MCF-7), colorectal (HCT116) and a HIF-1α knockout (HCT116-DNC2) cells 

were used. Hypoxia induced gene expression was investigated using quantitative 

reverse transcription-PCR, western analysis and immunohistochemistry. 

Results: Eight of 9 genes investigated were up-regulated at the RNA level in 

hypoxia (p < 0.003). As expected, there was variation between the cell lines. 

Further analysis of the Affymetrix microarray data revealed that the one gene 

not up-regulated was flagged absent in many samples, indicating a low signal 

to noise ratio. This gene may therefore be excluded from the gene signature 

based on its poor reliability. Only one of the genes was up-regulated under 

hypoxia in the HCT116 cells and appeared to be HIF-1α dependent. 

Conclusions: The knowledge based approach is a valid method for deriving 

molecular signatures and identifying genes involved in radiobiologically 

relevant cellular processes. 

Radiobiology : Radiosensitisers 

1499 poster 

HISTONE DEACETYLASE INHIBITORY ACTIVITY OF VALPROIC 

ACID IN GLIOBLASTOMA 

A. R. Chang 1 , I. H. Kim 2 , C. I. Park 2 

1 

SOON CHUN HYANG UNIVERSITY HOSPITAL, Radiation Oncology, Seoul, 


2 



Purpose: To evaluate the efficacy and toxicity of histone deacetylase inhibitor 

(HDACi), valproic acid (VPA) and radiotherapy in newly diagnosed glioblastoma 

multiforme. 

Materials: Between february 2002 and November 2006, 73 patients (median 

age, 53 years; range, 11-78 years) with histologically confirmed glioblastoma 

multiforme were treated with surgery followed by radiotherapy with or without 

chemotherapy. Intravenous or oral VPA was administered to 66 patients. 

Surgical extents were gross total resection in 19 patients (26%), subtotal resection 

in 35 (48%), and biopsy only in 19 (26%). The median radiation dose 

was 59.4 Gy, ranging from 52.2 to 61.2 Gy. 

Results: Four (6%) had a complete response (CR), 19 (26%) partial response 

(PR), 24 (33%) stable disease (SD), and 22 (30%) progressive disease 

(PD) after radiotherapy with or without VPA. Median time to progression 

was 10 months and median survival was 25 months. Median overall survival 

was 25 months in VPA treated patient group and 8 months in patient 

group treated without VPA (p=0.02). Favorable prognostic factors by univariate 

analyses on progression free survival were no neurologic symptom 

(p=0.01), ECOG performane status 0 or1 (p=0.01), existence of RT response 

(p

1500 poster 

INHIBITION OF G2 CHECKPOINT SIGNALLING AND RAD51 

KNOCKDOWN TO ENHANCE RADIO AND CHEMOSENSITIVITY IN 

HIGH GRADE GLIOMA 

S. Short 1 , C. Martindale 1 , M. Worku 1 , S. Bourne 2 

1 UNIVERSITY COLLEGE LONDON, Oncology, London, United Kingdom 

2 UNIVERSITY OF OXFORD, Gray Cancer Institute, Oxford, United Kingdom 

Purpose: To investigate which approaches to DNA repair inhibition are most 

effective in enhancing cytotoxicity of radiation, Temozolomide and combination 

treatment in high grade glioma cells 

Materials: Clonogenic survival assays and g-H2AX imunoflourescence were 

used to measure cytotoxicity and DNA DSB repair kinetics following exposure 

to clinical radiation doses, Temozolomide or combination treatment in 

TP53mut glioma cell lines T98G and U373. KU-5593 was used to inhibit 

ATM, caffeine to inhibit multiple kinase targets including ATM/ATR and siRNA 

targeted against Rad51 to reduce homologous recombination. Each of these 

treatments were then assessed for their effect on cell survival and DSB repair 

kinetics following IR, TMZ and combination treatment. Flow cytometry was 

used to assess changes in cell cycle distribution and treatment-induced cell 

cycle delay. Changes in damage signalling following cytotoxic treatment with 

and without repair inhibition were assessed using phospho-specific antibodies 

to signalling proteins on western blot. 

Results: The addition of temozolomide to clinical IR doses produced additive 

toxicity and increased initial DNA DSB. Combination treatment was associated 

with enhanced damage signalling to checkpoint proteins, however at 

24h no increased unrepaired DSB were apparent. Additional treatment with 

siRNA targeted against Rad51 produced significant further cytotoxicity and 

increased residual DSB at 24h following IR, TMZ and combination treatment. 

ATM inhibition increased the cytotoxic effect of IR but had less effect on TMZ 

cytotoxicity and was not associated with increased residual g-H2AX foci at 

24hours post combination treatment. Caffeine produced the most marked 

effect on clonogenic survival following treatment with IR + TMZ and was associated 

with abrogation of the damage induced G2 block. 

Conclusions: Additional inhibition of DNA DSB repair can significantly enhance 

the effect of IR and TMZ on glioma cell lines. Multiple kinase inhibition 

using caffeine is necessary to abrogate the G2 block following XR + TMZ 

and to enhance cyctotoxicity. Rad51 knockdown significantly enhanced the 

toxicity of XR, TMZ and combination treatment. Clinical agents which target 

Rad51 dependent repair or abrogate damage induced G2 block may be 

effective in enhancing the effect of radio-chemotherapy for high grade glioma. 

1501 poster 

INTRATUMORAL 224RA-LOADED WIRES COMBINED WITH 

CHEMOTHERAPY CAN DESTROY SOLID MALIGNANT TUMORS 

OF VARIOUS HISTOLOGICAL TYPES IN MICE AND PROLONG 

SURVIVAL 

T. Cooks 1 , G. Horev 1 , S. Reitkopf 1 , M. Schmidt 1 , G. Marshak 1 , L. Arazi 

1 , I. Kelson 1 , Y. Keisari 1 

1 TEL AVIV UNIVERSITY, Human Microbiology, Tel Aviv, Israel 

Purpose: Alpha particle radiation is highly lethal for cancer cells but has 

so far not been used in the treatment of solid tumors due to its short range 

in tissue. We have developed a new approach in which tumors are treated 

with intratumoral 224Ra-loaded wires that continually release by recoil shortlived 

alpha-emitting atoms. These disperse in the tumor and deliver a lethal 

dose over a region measuring 3-7 millimeters in size. The proposed method 

was termed Diffusing Alpha-emitters Radiation Therapy (DART). The present 

study examines the curative effects of a combination between the 224Raloaded 

wires and anti-tumor chemotherapy, against tumors of various histological 

types. 

Materials: Tumor cells from pancreatic (Panc02), squamous cell (SCC) 

(SQ2), and colon carcinomas (CT26), were injected subcutaneously into 

mice. Stainless steel 224Ra-loaded wire(s) (0.3 mm-diameter and 3-5 mm 

long) were inserted under anesthesia into tumors of 4-10 mm in diameter. 

Cisplatin, Gemcitabine, or 5-FU were administered concurrently. Animals 

were monitored for tumor development and survival. Also, an in-vitro set-up 

was used to assess killing of cancer cells by alpha particles. 

Results: Treatment of squamous cell carcinoma with a regimen of two (5 

mg/kg) i.v doses of cisplatin given concomitantly with two 224Ra-loaded wires 

(11.5-28.1 kBq), caused substantial growth arrest of 93%, and extended survival 

from 44 to 87 days. The combined treatment reduced both local tumor 

growth and metastatic spread to the lungs. Pancreatic tumors in C57BL/6 

mice were treated with one 224Ra-loaded wire, in combination with Gemcitabine. 

The combination of 224Ra wires (13-45 kBq) and Gemcitabine 

achieved the best local control of tumor growth. Significant reduction in tumor 

volume was achieved in such treated mice compared to all other treatment 

groups. 224Ra-loaded wires (15 kBq/wire), inhibited tumor growth of colon 

adenocarcinoma tumors (4-6 mm) by 45%, and even led to complete cure. 

Injection of 5-FU (75 mg/kg) with the 224Ra wire (17 kBq) augmented tumor 

destruction and growth retardation (35% compared to 224Ra and 5-FU 

alone, and 74% compared to no treatment). In vitro experiments with all tu- 

RADIOBIOLOGY : SIGNAL TRANSDUCTION 

S 477 

mor cells exposed to 224Ra atoms revealed a dose dependent killing of the 

tumor cells. The combined treatment with alpha particles and chemotherapy 

increased apoptosis and arrested cell proliferation to larger extent than any 

of the components alone. 

Conclusions: Diffusing Alpha-Emitting Radiation Therapy is an effective 

treatment to treat solid malignant tumors, and can be further potentiated in 

combination with chemotherapy. This combined treatment modality holds significant 

potential for the treatment of non-resectable human cancers. 

Radiobiology : Signal transduction 

1502 poster 

RADIATION-INDUCED UP-REGULATION OF SSTR1-5 IN SMALL 

CELL LUNG CANCER CELLS 

J. Oddstig 1 , P. Bernhardt 1 , O. Nilsson 2 , H. Ahlman 3 , E. Forssell-Aronsson 

1 

1 

LUNDBERG LABORATORY FOR CANCER RESEARCH, Radiation Physics, 

Göteborg/Malmö, Sweden 

2 

LUNDBERG LABORATORY FOR CANCER RESEARCH, Pathology, Göteborg/Malmö, 

Sweden 

3 

LUNDBERG LABORATORY FOR CANCER RESEARCH, Surgery, Göte- 

borg/Malmö, Sweden 

Purpose: Many neuroendocrine (NE) tumours overexpress somatostatin receptors 

(sstr), which is utilised in tumour therapy with radiolabelled somatostatin 

analogues, such as 177Lu-DOTA-Tyr3-octreotate. The somatostatin 

analogues bind to the sstr at the cell surface, and can be used in systemic 

radionuclide therapy of a tumour metastasis with unknown location. A high 

specific binding is of importance to get a high therapeutic response of the 

tumour and to spare the normal tissue. The sstr expression of different NE 

tumour cell lines can be up-regulated by hormones and growth factors, e.g. 

somatostatin, gastrin, estrogen or epidermal growth factor. There have also 

been indications of radiation-induced up-regulation of the sstr expression on 

NE tumour cells. Such an up-regulation could be used to further improve the 

binding of the radionuclides. The development of methods that increase the 

number of receptors on tumour cells is important. The aim of this study was 

to investigate the possibility of inducing up-regulation of the sstr expression 

on tumour cells by irradiation. 

Materials: Human H69 SCLC cells were irradiated to an absorbed dose of 

0.128.0 Gy and the sstr mRNA expression was measured by quantitative 

reverse transcriptase-polymerase chain reaction (Q-PCR) for all sstr subtypes 

(sstr1, 2 and 5) expressed. The binding of 177Lu-DOTA0-Tyr3-octreotate to 

the cells was measured 3 days after irradiation and compared to the binding 

to non-irradiated cells. 

Results: The mRNA expression for sstr1, 2 and 5 was up to two-fold increased 

in cells irradiated to absorbed doses higher than 0.25 Gy vs. nonirradiated 

cells. The binding of 177Lu-DOTA0-Tyr3-octreotate was accordingly 

2-3 times higher to irradiated cells vs. non-irradiated cells for all absorbed 

doses except for 0.25 Gy. 

Conclusions: The binding of 177Lu-DOTA0-Tyr3-octreotate was increased 

for the H69 SCLC cells after radiation exposure. This increase could be observed 

at very low absorbed doses in parallel with up-regulation of sstr1, 2 

and 5 mRNA. The results indicate that a diagnostic examination with radiolabelled 

somatostatin analogues could up-regulate the expression of sstr of 

relevance for subsequent therapy. These results may be important in optimising 

the treatment of tumours expressing sstr using radiolabelled somatostatin 

analogues. 

Radiobiology : Time dose fractionation 

1503 poster 

A LOW-DOSE HYPERSENSITIVE KERATINOCYTE RESPONSE 

TO FRACTIONATED RADIOTHERAPY IS MEDIATED BY GROWTH 

ARREST 

I. Turesson 1 , J. Nyman 2 , O. F. Qvarnström 1 , M. Simonsson 1 , M. Book 1 , 

I. Hermansson 2 , S. Sigurdardottir 1 , K. A. Johansson 3 

1 



2 



3 

GÖTEBORG UNIVERSITY, SAHLGRENSKA UNIVERSITY HOSPITAL, Depart-

S 478 RADIOBIOLOGY : TIME DOSE FRACTIONATION 

ment of Radiophysics , Gothenburg, Sweden 

Purpose: The existence of a hypersensitive radiation response to doses below 

0.5Gy is well established for many normal and tumour cell lines. There 

is also evidence for hypersensitive tissue responses for acute skin damage 

and kidney function in mice. The aim of this study was to investigate the dose 

response of basal clonogenic keratinocytes in normal skin to fractionated radiotherapy 

with low dose fractions. 

Materials: Skin punch biopsies from prostate cancer patients were taken 

before and during radiotherapy. Areas receiving daily fractions of 0.1, 0.2, 

0.45 and 1.1 Gy were biopsied at the same occasion after 1 week, 2-3 weeks, 

4-5 weeks and 6-7 weeks, in 22, 30, 24 and 12 patients respectively. The 

number of basal keratinocytes/mm of the epidermis were determined. All 

melanocytes were excluded. Cell cycle progression in the basal cell layer of 

the epidermis was determined by staining for the molecular markers: Ki-67, 

Rb, cyclin A, cyclin B, phosphoH3 and p21. Cell death was quantified by 

γH2AX staining. Clonogenic stem cells were distinguished from clonogenic 

progenitor cells by BMI-1 staining. The number of stained keratinocytes in 

the basal layer were counted. 

Results: A general dose dependent decrease in basal keratinocyte density 

was observed for all investigated doses throughout the treatment course. In 

more detail, the dose response revealed a low-dose hypersensitivity effect for 

all doses and time points (p

leucopoenia G4). No acute local toxicity of any grade was observed. 

Conclusions: In our experience UFRC (total dose delivered ranging from 

320 cGy to 1280 cGy) was well tolerated: no acute local toxicity was observed. 

The response rate seems interesting and prospective phase II studies 

are ongoing. 

1507 poster 

LOW-DOSE HYPERSENSITIVE H2AX RESPONSE AND INFRE- 

QUENT APOPTOSIS IN EPIDERMIS FROM RADIOTHERAPY 

PATIENTS 

F. Qvarnström 1 , M. Simonsson 1 , J. Nyman 2 , K. A. Johansson 3 , H. Garmo 

4 , M. Book 1 , I. Hermansson 2 , I. Turesson 1 

1 



2 



3 


of Radiophysics , Gothenburg, Sweden 

4 

REGIONALT ONKOLOGISKT CENTRUM, AKADEMISKA SJUKHUSET, Uppsala, 

Sweden 

Purpose: A low-dose hypersensitivity to radiation can be observed in vitro 

for many human cell types in terms of increased cell kill per dose unit for 

doses below 0.5Gy. Quantification of the double strand break marker γH2AX 

in samples taken in clinical radiotherapy practice has the potential to provide 

important information about how induction and repair of severe DNA damage 

and apoptosis are linked to low-dose hypersensitivity. 

Materials: The effects of exposure to low doses (0.05-1.1Gy) were investigated 

in skin biopsies taken from prostate cancer patients undergoing the 

first week of radiotherapy. γH2AX foci and apoptotic cells were visualised by 

immunohistochemistry and quantified by image analysis. 

Results: Counting number of γH2AX foci in cells from biopsies taken 30 minutes 

after a single fraction revealed a low-dose hypersensitivity below 0.3Gy 

(p

S 480 RTT 

of two treatment phases: with identical fractionation patterns (2 Gy/fr: 0- 

46+0-22 Gy) and with varied fractionation patterns (2 Gy/fr: 0-46 Gy+1.1 

Gy/fr: 0-22 Gy). For all testcases, absolute dose differences were calculated 

as |dORG-dEQD2| among all matrix elements for minimum, maximum and 

mean doses; between specific matrix elements i for maximum and mean differences 

|dORG(i)-dEQD2(i)|; relative errors as (dORG-dEQD2)/dEQD2; radiobiological 

model predictions as gEUD, LKB and Relative Seriality outputs 

(evaluated for a serial and parallel organ structure at different organ tolerance 

levels). 

Results: The absolute absorbed dose differences in Gray (Gy) for minimum, 

maximum and mean doses as well as voxel-by-voxel comparisons 

of maximum and mean differences were greater for treatment sets 

with varied fractionation patterns: [3.9±1.9; 3.6±2.1; 4.2±1.6] versus 

[3.3±1.8, 2.3±1.7 , 3.0±1.5] and [5.5±1.8, 3.3±1.2] versus [4.5±1.8 and 

2.5±1.1] respectively. The corresponding relative errors were [30.8±16.1%, 

10.6±10.0%, 16.0±10.8%] versus [27.1±16.6%, 6.1±8.5%, 11.7±9.7%] 

and [31.2±15.6%, 19.3±11.6%] versus [27.5±16.0%, 15.1±10.9%]. The 

effect was more notable in model prediction differences of a parallel than of a 

serial organ structure: 15-51% versus 9-28% (NTCP) and 4.1±1.6 Gy versus 

3.4±1.9 Gy (gEUD) respectively. 

Conclusions: This investigation shows that voxel-by-voxel corrections using 

the LQ model are necessary in order to obtain representable dose estimations 

in multiple phase’s treatments with varied dose distributions and fractionation 

patterns. 

RTT 

1511 poster 

A FORMAL EVALUATION OF PROSTATE VERIFICATION PROCE- 

DURES IN THE SIMULATOR 

M. Keaveney 1 , A. Clayton-Lea 1 , L. O’Neill 2 , B. McCafferty 1 , S. Burke 1 , 

J. McCartan 1 , R. McCloy 1 , C. Brett 1 , P. Sutton 1 , E. O’Shea 1 , P. Thirion 3 

1 


of 

2 

ST. LUKE’S HOSPITAL, Department of Radiotherapy Planning, Dublin, 

Ireland Republic of 

3 

ST. LUKE’S HOSPITAL, Radiation Oncology, Dublin, Ireland Republic of 

Purpose: In conformal RT the treatment fields and iso-check produced by 

the planning system require verification this may be done either at the treatment 

unit (day 1) or using a standard simulator. This verification procedure 

represents a random event, therefore any iso-centre correction at this early 

stage could introduce a systematic error. The objective of this study was to 

investigate the feasibility and safety of introducing an action level regarding 

iso-centre correction at time of verification in conformal localised prostate RT, 

in our institution. 

Materials: Patient eligibility criteria: - 1. Treated by localised 3-DCRT. 2. 

In supine position. 3. Iso-centre shift not required at planning (original CTplanning 

tattoo applicable). In our institution, verification is done using a standard 

simulator, by acquiring standard A/P and Lateral iso-centre check, which 

is visually compared to the printed DRRs. The study protocol set a twodimensional 

(2D) action level as follows: - any displacement of ≥4mm in any 

direction (x,y,z) was corrected i.e, patient was re-marked (new iso-centre set 

for treatment duration new skin marks). Subsequently, iso-check at weeks 1, 

3 and 5 were used to determine any systematic set-up error (visual comparison 

between megavoltage portal film and kilovotage simulation film). 

Results: 41 pts were recruited to this study over a 6-month period full data 

was evaluable on 39 of these (2 pts had premature treatment interruption). 

Of the 39 evaluable patients, 9 patients (23%) were re-marked i.e, corrected 

group; 30 pts required no moves (17 pts below action level; 13 pts - no 

displacements) i.e, non-corrected group. Systematic errors of ≥5mm were 

detected in a total of 4 (10%) of the 39 evaluable patients: 1 pt (11%) in the 

corrected group and 3 pts (10%) in the non-corrected group (p=ns). 

Conclusions: This study shows that it is both feasible and safe to implement 

an iso-centre correction with an action level of ≥4mm at time of verification 

for localised prostate RT, in the specific setting of our institution. This study 

has provided a template for further evaluation of implementing an action level 

for iso-centre correction at verification in other tumour sites and/or evaluation 

of same using IGRT on-board imaging. 

1512 poster 

A NEW DEVICE FOR THE MEASUREMENT OF THE ABSORBED 

DOSE TO WATER FOR LOW-ENERGY X-RAYS AND LOW DOSE- 

RATE BRACHYTHERAPY SOURCES 

T. Schneider 1 , B. Lange 1 , M. Meier 1 , H. J. Selbach 1 , L. Tägtmeyer 1 

1 PHYSIKALISCH-TECHNISCHE BUNDESANSTALT, Department of Dosimetry 

for Radiation Therapy, Braunschweig, Germany 

Purpose: Dosimetry for low-energy interstitial brachytherapy x-ray sources is 

currently based on source calibrations in terms of the reference air kerma rate 

(RAKR) or air kerma strength (AKS). As patient dosimetry is based on the absorbed 

dose to water, a conversion formalism as published by the American 

Association of Physicists in Medicine (AAPM), known as the TG- 43 protocol 

and its update (TG-43U1), is required. The overall standard uncertainty in 

deriving the dose at a point near the source from RAKR or AKS using the 

protocol is estimated to be about 5%. Deviations of 5% between prescribed 

and administered doses have to be regarded as clinically significant. A direct 

calibration in terms of the absorbed dose to water would reduce this uncertainty. 

Materials: A large, air-filled, parallel-plate extrapolation chamber in a phantom 

of water-equivalent material was constructed to serve in future as a primary 

standard for the direct measurement of the absorbed dose to water. 

The method of evaluation, which will be described in this work, is based on 

a Monte Carlo-determined conversion factor C(xi,xi+1) to be applied to the 

difference of the ionization charge for the two plate separations xi and xi+1. 

The design of the chamber follows the design of PTB’s large-volume extrapolation 

chamber (GROVEX), with two exceptions: First, the entrance and the 

back plate are made of a water-equivalent material. Thereby, the thickness of 

the entrance plate defines the measurement depth within the water phantom. 

Secondly, the cross section of the measuring volume is defined by means of 

an aperture and not through the size of the measuring electrode. 

Results: The preliminary studies, as well as the Monte Carlo simulations 

leading to the method of evaluation and to the changes in the chamber design, 

will be summarized. The conversion factors determined by means of 

Monte Carlo simulations are presented for several radiation fields with different 

x-ray spectra. 

Conclusions: First measurements with the chamber will be shown and compared 

to results obtained by other techniques.

1513 poster 

A RANDOMISED STUDY COMPARING THE DOSIMETRY AND 

RADIATION INDUCED SKIN REACTION IN BREAST CANCER 

PATIENTS TREATED IN THE LATERAL DECUBITUS POSITION WITH 

STANDARD(CURRENT) SUPPORT PADS VERSUS NEW MODIFIED 

SUPPORT PADS 

D. Harper 1 , L. Coleman 1 

1 MATER PRIVATE HOSPITAL, Radiotherapy Department, Dublin, Ireland 

Republic of 

Purpose: Lateral Decubitus is a technique to treat patients with larger breasts 

by lying them on their side for Radiotherapy. By doing so the seperation of 

a larger breast is significantly reduced compared with conventional supine 

techniques. It also helps reduce the volume of underlying lung treated. The 

purpose of the study is to determine whether we can simplify the treatment 

plans and improve Dosimetry (Dose Distribution) and hence improve the radiation 

induced skin reaction in breast cancer patients treated in the Lateral 

Decubitus position by modifying the current breast support pads used. The 

objective is to randomise patients for treatment with either the current pads 

or the new modified ones. Each treatment plan will be analysed for simplicity/complexity, 

homogeneity (even dose distribution) and other factors. We 

propose that by modifying the shape of the support pads we can improve 

dose homogeneity with simpler plans and thus improve the skin reactions in 

patients treated with this technique. 

Materials: The purpose of the support pad in the Lateral Decubitus technique 

is to support the breast for treatment and to ’flatten’ the breast into a 

even ’block’ shape to aid the treatment planning. We did not change the material 

of the support pads (polystyrene) but simply modified the shape of the 

pads. The hypothesis of the study is that the current treatment pads are not 

optimally shaping the breast into a ’block’ of homogenous tissue. Because of 

this the treatment plans are becoming more complex to achieve dose homogeneity 

within the breast and as a result we feel certain patients are having 

worse skin reactions. Currently the shape of the pad is a steep gradient edge 

which lies in against the chest wall of the patient which levels off abruptly 

to a flat surface to support the majority of the breast tissue. We believe the 

steep edge is hindering dose homogeneity as the pocket of tissue lying between 

this edge and below the flat edge on which the rest of the breast lies 

largely prevents the creation of an even ’block’ shape in the majority of patients. 

We propose a ’wedge’ shaped pad which will eliminate this steep edge 

and help create a more ’even’ shaped breast. The first part of the study will 

look at the dosimetry achieved in each group of patients. Analysis will be 

performed on the treatment planning system and will be assessed for homogeneity, 

simplicity/complexity etc. The second part of the study will look at 

the acute radiation induced skin reaction at treatment on a weekly basis using 

the RTOG skin grading protocol as an assessment tool. At assessment 

we divided the breast into 8 sections (4 quadrants, inf mammary fold, lateral 

border, axilla/axillary tail and nipple/areola) for analysis. Patients were randomised 

prior to their planning CT to either the old support pad or the new 

support pad for treatment. Each area was individually graded after fractions 

5, 10, 15, 20 and 25. Inclusion criteria included standard fractionation (50Gy 

in 25 fractions), clinically large breast, and treatment energy of 6MV. 

Results: Preliminary data for dosimetric analysis shows a greater level of 

homogeneity achieved in the new pad verus the old pad with less complex 

planning needed in this group also. We were also able to create a predictive 

tool for hot-spot location from the planning system. This data collected 

correlated well with the skin reaction seen on set in both groups but more so 

in the group treated on the new support pads. Data collected in relation to 

the acute skin reaction shows even distribution of RTOG grade 3 reactions 

in both groups when analysed simply for old versus new pad however when 

the groups are sud-divided into cohorts, other contributing factors (chemo, 

hypertension, allergies, obesity etc) are clearly indicative of increased skin 

reaction. 

Conclusions: This is only preliminary data at present and we hope to have 

a full analysis for our poster presentation at the conference. So far however 

there is a clear trend toward greater homogeneity in our trial pad group. With 

this should come the well documented benefits of greater homogeneity in 

the breast e.g. cosmesis etc. This should benefit this cohort of patients 

with larger breasts and help reduce planning time. It has also helped us to 

highlight a more specific group of patients who are more likely to present with 

hightened skin reaction during their treatment and thus present possibilities 

for greater management of skin reactions in these patients. More data is 

needed however to see if less skin reaction is seen in patients treated on the 

new pad versus old when correcting for these contributing factors. 

1514 poster 

RTT 

S 481 

A SERIES OF CASE STUDIES INVESTIGATING VOLUMETRIC AND 

SPATIAL CHANGES IN HEAD AND NECK PATIENTS UNDERGOING 

IMRT AND THE SUBSEQUENT ADAPTIVE PROCESS. 

R. Height 1 , M. Wada 1 , C. Lawford 1 , M. Lawlor 1 , M. Rolfo 1 , M. Yoho 1 , 

R. Stewart 1 , D. Lim Joon 1 , V. Khoo 2 

1 AUSTIN HEALTH, Radiation Oncology Centre, Melbourne, Australia 

2 ROYAL MARSEDEN HOSPITAL, Radiation Oncology Centre, Surrey, United 

Kingdom 

Purpose: IMRT achieves high doses to target volumes whilst minimising the 

dose to adjacent normal tissues. Due to the complex and conformal dose distributions 

produced, the treatment is dosimetrically susceptible to geometric 

deviations. Precise positioning and minimisation of distortional changes via 

an accurate verification process and effective immobilization are vitally important 

to ensure deviations are managed and minimised. Three mechanisms / 

situations with distortional variations are presented. 

Materials: Retrospective analysis was completed on three patients with SCC 

of the head and neck treated with IMRT. Geometric changes observed on 

daily CBCT prompted rescanning using the sim CT. The mechanisms leading 

to rescanning included tumour progression and regression (i.e. large neck 

node mass, case 1), systematic set up distortional error despite immobilisation 

(case 2) and significant weight loss (case 3). The planned beam fluence 

was overlaid on the repeat sim CT. Analysis was completed using absolute 

volume and geometric displacement of the gross tumor volumes (GTV) 

and organs at risk (OAR). External contour change was correlated to weight 

loss. Dosimetric assessment included dose volume histogram (DVH) data 

and comparison of the isodose distribution in all cases. 

Results: The left neck node in case 1 increased in size by 15% in the 12 

days between sim CT and the first treatment, resulting in a decrease of the 

V95 from 95.1% to 78.6%, requiring replanning. The nodal volume then regressed 

by fraction 30 by 72%, this continued to be covered by the 95% isodose 

line. Systematic positional distortion due to set up error (case 2) lead to 

a significant shift of the bilateral parotids, brainstem and the spinal cord in the 

posterior direction. The mean dose to the right and left parotids increased 

by 5Gy and 14Gy respectively. The maximum dose to the brainstem and 

spinal cord increased by 16Gy and 3.3Gy respectively. Case 3 experienced 

11% weight loss yet the GTV continued to receive the prescribed dose and 

change in dose to OAR was minimal, replanning was not required. 

Conclusions: Information from daily 3D images allows assessment of interfractional 

geometric changes during treatment. Presented cases illustrated 

mechanisms which resulted in significant underdosage of the target and / or 

overdosage of the organs at risk. Precise assessment of delivered dose is 

nonetheless difficult without the ability to deform 3D image sets accurately 

and to generate cumulative dose distributions. Careful and regular assessment 

of image data to identify tumor progression, systematic set up discrepancy 

and/ or response related changes in the patient is needed to prompt 

replanning. 

1515 poster 

ACCELERATOR PERFORMANCE IN BEAMS WITH FEW MONITOR 

UNITS 

I. Kristensen 1 , P. Munck af Rosenschöld 1 , B. Blad 1 


Purpose: The number of patients receiving intensity modulated radiotherapy 

treatment (IMRT) is steadily increasing in our clinic. The technique sets high 

demands on verification of the planned treatment but also high demands on 

the accelerators performance and delivery of the prescribed dose. IMRT is 

presently delivered using the step-and-shoot technique at the clinic. Several 

of the planned segments will be given with few monitor units. This indicates 

that the dosimetric property of the beam in the accelerator’s start up phase 

is more important than in conventional radiotherapy. We have studied the accelerator 

start-up phase using the MapCHECK TM (Sun Nuclear Corporation) 

2D diode array. This instrument was developed as a tool for quality control of 

IMRT treatments in radiotherapy. It is has a grid of 445 diode detectors placed 

at 2 cm water equivalent depth. The aim of this work is to evaluate flatness 

and symmetry during the start-up phase of the accelerator in regard to the 

low number of monitor units used in the IMRT step-and-shoot technique. 

Materials: To obtain measurements, the detector is placed on the treatment 

couch with the detector plane at isocenter (source-detector distance =100 

cm). Best resolution over the largest area is obtained by positioning the detector 

with its diagonals aligned with the major axis (figure 1). Raw data 

are imported into an excel worksheet. A macro extract profiles along the 

major axis, calculates flatness, symmetry and field size. Profiles has been 

measured for 1, 3, 5, 7, 10, 15, 20, 100 MU respectively. 100 MU is used 

for obtaining profiles for flatness and symmetry in the weekly quality control 

programme where the MapCHECK TM is used. Measurements have been performed 

at three linear accelerators used for IMRT, all Electa, one Precise and 

two Synergy. All measurements are made at 6 MV. 

Results: Preliminary results shows noise at 1 MU, but already at 3 MU the 

profile is stabilised and compares quite well to the profile measured at 100

S 482 RTT 

MU. The difference between the 1 MU profile and the 100 MU profile is probably 

due to the detector response. This is compared with measurements 

made with the BMS diode array.Figure 1. The figure shows the beam profile 

from one accelerator, from left to right; 1 MU, 3 MU, 100 MU. The different 

curves represent different measurements. 

Conclusions: Using the diode array (MAPCheck) we have been able to confirm 

that our Elekta machine is able to deliver beams with a reasonable flat 

profile down to 3 MU (6MV). Consequently, IMRT segments with 3MU or more 

can be used clinically. 

1516 poster 

ARE DAILY ON-LINE MATCHING USING IMPLANTED GOLD MARK- 

ERS IN THE PROSTATE NECESSARY AND PRACTICABLE? 

A. L. Gustafsson 1 , A. Larsson 1 , C. Rudolfsson 1 , H. Jung 1 , M. Lagerlund 

1 , S. Johnsson 2 

1 KALMAR COUNTY HOSPITAL, Oncology, Kalmar, Sweden 

2 KALMAR COUNTY HOSPITAL, Radiation Physics, Kalmar, Sweden 

Purpose: In a pre-study including 17 patients with implanted gold markers 

we studied the intra-fractional movements of the prostate during the delivery 

of the two lateral opposed boost fields. Despite that the markers were 

in correct position when the first lateral field was delivered, almost 1/3 of 

the patients had to be corrected on-line before the second lateral field was 

delivered. Since the boost is delivered with a relatively simple and fast technique, 

we expect intra-fractional prostate movements to be even more pronounced 

during the treatment of the larger prostate volume, which is done 

with a more complex 5-field technique. The primary objective is to quantify 

intra-fractional prostate movements using daily on-line portal imaging during 

the whole course of treatment. Extensive use of portal imaging implies an 

increased workload and our secondary objective is to find new practical routines 

in order to make this new strategy work in practice. 

Materials: All ’intermediate’ and ’high risk’ prostate patients treated with external 

radiotherapy between January and August 2008 are to be included 

in this study. A vacuum cushion for knee and feet fixation is used and the 

patients are planned and treated with three gold markers implanted in the 

prostate. The markers are easily detected on the simulator (reference image) 

and portal vision images. A 5-field technique (one frontal, two lateral and two 

oblique frontal fields) is used up to 70Gy and an extra boost (4x2Gy) is given 

with two lateral opposed fields to a smaller volume. On each fraction, portal 

images are acquired for the lateral and frontal fields which are then matched 

with the reference images. The patient is moved if the displacement of the 

gold markers is >3mm for the 5-field technique and >2mm for the boost fields, 

whereupon new portal images are acquired to verify the new position. 

Results: Data collection for the intra-fractional prostate movements is in 

progress and will be presented later. The number of acquired portal images, 

however, has increased considerably and we have implemented new routines 

to optimize the added clinical workload. The radiotherapy technologists have 

been educated and supervised during a period of time and are now in charge 

of the on-line matching, reviewing and approval procedure. An off-line review 

is done by the oncologist once a week and feedback is given regularly 

to the radiotherapy technologists. The 5-field technique takes on average 

10 minutes to deliver, which includes acquisition of portal images, matching, 

reviewing, possible couch movements and re-matching. 

Conclusions: The pre-study indicate that on-line portal imaging should be 

used on a daily basis for all frontal and lateral fields. The increased workload 

has enforced new clinical routines and this study shows that the radiotherapy 

technologists can take responsibility for many parts of this new on-line 

correction strategy. 

1517 poster 

BLOOD BIOMARKERS COMBINED WITH CLINICAL FACTORS 

YIELD A BETTER PREDICTION MODEL FOR 2-YEAR SURVIVAL 

OF NON-SMALL CELL LUNG CANCER PATIENTS TREATED WITH 

(CHEMO) RADIOTHERAPY 

S. Yu 1 , C. Dehing-Oberije 2 , D. De Ruysscher 2 , G. Fung 1 , S. Krishnan 1 , 

B. Rao 1 , P. Lambin 2 

1 

SIEMENS MEDICAL SOLUTIONS USA, INC., CAD and Knowledge 

Solutions, Malvern, USA 

2 


Purpose: A large group of non-small cell lung cancer (NSCLC) patients are 

currently treated with radiotherapy combined with chemotherapy. Most of the 

prognostic studies for this group of patients depend only on clinical factors 

such as age, WHO performance score, stage and size of the tumor. The objective 

of this study was to develop a prognostic model by combining various 

blood biomarkers, related to hypoxia, acidosis and inflammation, with clinical 

factors for better survival prediction of NSCLC patients, treated with (chemo) 

radiotherapy. 

Materials: Blood samples were collected for 82 consecutive inoperable 

NSCLC patients, stage I-IIIB, treated radically with (chemo) radiation. Six 

blood biomarkers, which include Osteopontin (OPN) corrected for creatinin 

clearance, Carbonic Anhydrase 9 (CA9), Interleukin-6 (IL6), Interleukin- 

8 (IL8), Carcino-embryonic Antigen (CEA) and Cytokeratin Fragment 21.1 

(CYFRA), were measured for these patients. The 2-norm Support Vector 

Machines were used to build a prognostic model for 2-year survival, using 

clinical factors combined with blood biomarker measurements. This is then 

compared with the prognostic model using the clinical factors only. Performance 

of the model was expressed as the AUC (Area Under the Curve) of 

the Receiver Operating Characteristic (ROC) and assessed using leave-oneout 

(LOO) cross-validation. The maximum value of the AUC is 1.0; indicating 

a perfect prediction model. A value of 0.5 indicates that patients are correctly 

classified in 50% of the cases, e.g. as good as chance. The study was approved 

by the medical-ethical committee; all patients gave written informed 

consent for participation in this trial. 

Results: The final multivariate model consisted of three clinical factors: WHO 

performance status, number of positive lymph node stations and gross tumor 

volume, and three blood biomarkers: OPN (corrected for creatinin clearance), 

IL8 and CEA. The AUC, assessed by LOO cross-validation, was 0.85 (95% 

CI 0.77-0.94), which is significantly better than the prognostic model using 

only clinical factors (AUC 0.74, 95% CI 0.62-0.87). Based on the ROC curve, 

the final model is able to correctly predict 38% (9 pts) of the true positives 

(TP) without any false positive (FP), and correctly predict 41% (24 pts) of the 

true negatives (TN) without any false negative (FN). 

Conclusions: By combining these blood biomarkers together with clinical 

factors, the prognosis model successfully estimates 2-year survival of individual 

patients, and the performance, assessed in the leave-one-out AUC score, 

is significantly better than the prognosis model using only the clinical factors 

(AUC: 0.85 vs 0.74). The model could assist clinicians in clinical decisionmaking 

and treatment tailoring. 

1518 poster 

CAN A RADIOTHERAPY DEPARTMENT BE ORGANIZED WITHOUT 

TIMEPLANNING FOR PATIENTS? 

C. Grahn 1 

1 SAHLGRENSKA UNIVERSITY HOSPITAL, Radiotherapy Department, 


Purpose: In the radiotherapy department at sahlgrenska University Hospital 

the patients are allowed to choose their own treatment time.This drop-in 

system was developed in march 2006. 

Materials: The pilot study involved 40 patients,most of them women with 

treatment for breast cancer.The oncology nurses at the radiotherapy department 

treatment room 1started with the drop-in system. The treatment room 

is open Monday to friday between 7.15-16.00. Drop-in has many advantages 

both for patients and staff.The patients are more independent and have a 

freedom of choice on the basis of their health or activity.For example ,the 

patientwho want to workduring the treatment has the freedom of choosing a 

time that suits them.Or for the patients who have travelling time or problems 

with pain,will not have the stress of get in time for a booked appointment. 

Benefits for staff are less paperwork and time planning is no longer a source 

of irritation.

Results: What did the patients think about drop-in? We used a questionnaire 

to evaluate drop-in. 47 patients answered and every one had a benefit from 

drop-in and they point out the flxibility and that the interruptions in their daily 

life were minor. 

Conclusions: Today three treatment rooms out of nine are using drop-in 

for their patients. Average of 120 patients are using the advantage of dropin 

every day. Drop-in system are now permenent in the department. The 

answer to the question, can a radiotherapy department be organized with out 

booking of time slots? definitely yes and with a very good result. 

1519 poster 

EFFECT OF INTEROBSERVER VARIATION ON DOSE DISTRIBU- 

TIONS OF SIMULTANEOUS INTEGRATED BOOST (SIB) BREAST RT 

S. den Hollander 1 , A. van Mourik 1 , M. Van Heumen 2 , C. Van Vliet- 

Vroegindeweij 1 



2 DR. BERNARD VERBEETEN INSTITUUT, Department of Radiation Oncology, 


Purpose: New planning systems and techniques result in more conformal 

dose distributions. Delineating a boost target volume for breast cancer is relatively 

new and interobserver variation is a fact. Little is known about the 

quantitative effect of interobserver variation on the dose distribution. This 

study investigated how much the coverage of a dose distribution planned on 

an initial boost planning target volume (PTVb) changes when evaluating on 

a PTVb of other physicians. This effect was examined for two planning techniques. 

Materials: CT-scans of 5 patients after breast conserving surgery were used. 

Three physicians delineated the tumor bed and subsequently expanded to 

CTV(1.5cm minus histologically tumor free margin) and PTV(0.5cm). Two 

simultaneous integrated boost (SIB) IMRT planning techniques were used 

(PTVb 31 x 2.38Gy): 1) SIB1: Simultaneous inverse optimization of 2 tangential 

glancing open fields combined with 2 tangential IMRT fields for the 

breast and 2 tangential open fields for PTVb. 2) SIB2: like SIB1 but with 1 orthogonal 

and 2 tangential IMRT fields for PTVb Both techniques were used in 

combination with all PTVb, resulting in 3x2 plans per patient. Afterwards the 

coverage (V95) of all six dose distributions was evaluated on all three PTVb. 

Results: Coverage of the PTVb used for planning was >98% in all cases. 

SIB2 resulted in a much tighter dose distribution. Coverage of PTVb in the 

presence of interobserver variation remains more than 90% in the majority 

of the cases for SIB1 (Table 1). For SIB2 a minimum of 80% coverage is 

observed for most plans. Visual inspection of the plans showed that low coverage 

(

S 484 RTT 

as chemotherapy and hormonal therapy and the scheduling of radiotherapy 

in relation to reconstruction will also be presented. 

Conclusions: 

1522 poster 

FOUR DIMENSIONAL CONE BEAM CT GUIDED RADIOTHERAPY 

FOR LIVER TUMOR USING IMPLANTED MARKERS 

S. van Beek 1 , E. Jansen 1 , C. Rasch 1 , M. van Herk 1 , J. J. Sonke 1 



Purpose: Recently, promising results have been reported for stereotactic 

body radiotherapy (SBRT) of primary and metastatic liver cancer. SBRT is 

characterized by a low number of fractions, a high ablative dose and a high 

precision of treatment delivery. For conventional RT of liver cancer, the bony 

anatomy is often used as a surrogate for tumor location, which is likely to be 

too imprecise for SBRT. We propose the use of fiducial markers implanted in 

the proximity of the lesion as a surrogate for tumor location and four dimensional 

(4D) cone beam CT (CBCT) guidance for accurate registration and 

correction of the marker location. The purpose of this study was to evaluate 

the feasibility of the proposed correction strategy and to quantify the interfraction 

baseline shifts (displacement relative to the bony anatomy) of liver 

tumors. 

Materials: Four patients with metastasic liver cancer and a variety of implanted 

markers (2 4 markers per patient) were included in this study so 

far. Patients were treated with 15 fractions of 3 Gy with an online or offline 

bony anatomy setup correction protocol using CBCT guidance (6 to 15 CBCT 

scans per patient). Retrospectively, markers were localized using locally rigid 

registration on 4D CBCT. Baseline variations were quantified by the difference 

in the (time weighted average) position of the markers and the bony anatomy. 

The results were analyzed in terms of group mean (M), standard deviations 

of the systematic (S) and random (s) errors for the translations. 

Results: The average peak-to-peak tumor amplitude assessed by 4D CBCT 

was 1.2 cm [range 0.7 cm - 1.6 cm]. The results of the interfraction baseline 

variation are shown in Table 1. Interestingly, the systematic error (S) was 

significantly bigger than the random error (s) indicating that the planning CT 

was a poor representation of the patients tumor location during treatment. 

Conclusions: Online 4D-CBCT guided RT for liver cancer patients using 

implanted markers was feasible. Substantial baseline variations have been 

observed over the course of RT of liver cancer patients indicating the limited 

accuracy of bony anatomy alignment. SBRT for liver cancer therefore 

requires image guided correction strategies and a 4D-CBCT guided protocol 

is currently being implemented in our clinic. 

1523 poster 

GEOMETRICAL UNCERTAINTIES IN SOFT TISSUE SARCOMAS OF 

EXTREMITIES 

A. Betgen 1 , R. Haas 1 , J. J. Sonke 1 

1 THE NETHERLANDS CANCER INSTITUTE/ANTONI V LEEUWENHOEK 


Purpose: Standard of care for almost all extremity soft tissue sarcomas 

(ESTS) patients is surgery, followed by radiotherapy (RT). Several studies 

however, show benefit of preoperative RT, especially concerning late morbidity 

endpoints such as fibrosis and joint stiffness. Therefore, the timing of 

radiation in ESTS patients is under debate. Generous margins are often applied 

for microscopic disease (GTV to CTV 1.5 cm except in the directions 

of bones and fasciae, and 3 cm longitudinally) and geometrical uncertainties 

(CTV to PTV 1.0 cm in all directions). The impact of the geometrical uncertainties 

with respect to ESTS during preoperative RT is largely unknown, 

because the quantification of these uncertainties has never been subject to 

extensive research. The purpose of this study was to quantify volume and 

positional changes of the Gross Target Volume (GTV) during preoperative RT 

and investigate the possibility for more advanced correction strategies. 

Materials: Ten patients with lower limb ESTS were included in this retrospective 

study. Planning CT-scan and CBCT-scans acquired at the start of 

the treatment, after one week and at the end of the five weeks treatment 

were used for delineation of the GTV. Delineation was performed after a registration 

on bony anatomy, which was used as a surrogate for tumor position 

during treatment for setup correction. The GTV volume was calculated, as 

well as the displacement of the GTV center of gravity (COG) relative to the 

planning CT-scan. 

Results: In four patients volumes did not change more than 3%. However, 

significant changes were discovered in six patients. In three patients an increase 

of the GTV volume was measured (10%, 19% and 26%) and in three 

patients a decrease was noted (12%, 17% and 23%). The COG of these 

delineations changed for the last CBCT with a mean vector length of 0.39 

cm (range 0.03 0.86 cm). The changes in the increasing volumes are always 

away from the bones, and vice versa in the decreasing volumes in the 

direction of the bones. 

Conclusions: Substantial geometrical uncertainties have been observed 

during preoperative RT of ESTS, largely associated with increase and decrease 

of the GTV volumes. Clinically applied margins were adequate to 

account for these uncertainties. To further reduce morbidity, reduction of geometrical 

uncertainties and margins are essential. This might require soft 

tissue guidance because the bony anatomy is not always a good surrogate 

for GTV position and adaptive re-planning to account for volume changes. 

1524 poster 

HDR PROSTATE MONOTHERAPY: THE ROTTERDAM LOGISTICS 

M. Roos 1 , S. Aluwini 1 , C. de Pan 1 , I. K. Kolkman-Deurloo 1 


Purpose: After 7 years experience with HDR brachytherapy as a boost for 

early stage prostate cancer and more than 200 patients treated with excellent 

results, we want to report our new treatment for the same group of patients 

using ultrasound/CT guided transperineal (HDR) brachytherapy as monotherapy 

in Rotterdam, evaluating the logistic aspects. 

Materials: Between September 2007 and February 2008 15 patients underwent 

HDR monotherapy administering 38 Gy in 4 fractions within 36 hours. 

(First day 2 fractions with 6-hour interval, the second day 2 fractions). The 

treatment procedure consisted of epidural anesthesia, followed by ultrasound 

imaging of the prostate. The optimal needle positions were determined and 

on average 20 needles (range 17- 23) were inserted. After implantation a cystoscopy 

was performed to assess the needles depths in relation to the bladder. 

The target and critical structures were delineated on a CT scan made 

after implantation. A treatment plan was made using Plato BPS 14.2. The 

dose distribution was optimized using inverse optimization followed by graphical 

optimization. Needle positions were checked with serial lateral x-rays 

before each fraction, using implanted markers and bladder contrast. Time 

consumption of all steps was registered. 

Results: Figure 1 shows the average time consumption of each step and 

time lapsed between steps. Large variations are seen on the CT scanning, 

delineation of target and OAR and treatment planning. Also time lapsed between 

these steps varies considerably. The total treatment procedure took on 

average of 5h 51min (+/- 1h 11min), necessitating administering the second 

fraction after office hours 

Conclusions: HDR brachytherapy as a monotherapy is feasible as a treatment 

for early stage prostate cancer. Administering two treatments after implantation 

within office hours proved to be a big challenge. However time 

consumption is steadily decreasing and is now at an acceptable level. A significant 

decrease in the total procedure time is expected after introduction of 

real time treatment planning based on ultrasound imaging for organ delineation 

during implantation. 

1525 poster 

IMPACT OF MULTI LEAF COLLIMATOR LEAF WIDTH ON 3D 

CONFORMAL RADIOTHERAPY TREATMENT PLANS 

G. Christensen 1 , A. Bäck 1 , K. Bünte 1 , K. Langenes 1 , N. Drugge 1 , K. A. 

Johansson 1 

1 SAHLGRENSKA UNIVERSITY HOSPITAL, Therapeutic Radiation Physics, 


Purpose: It would be valuable to appraise the benefits of a reduced leaf 

width before the start of treatment planning to be able to optimise the choice

of treatment machine. The objective was to study which treatment situations 

that yields the largest benefits. 

Materials: Three MLC designs with different leaf width at isocentre were 

used; Varian Millennium 80-leaf MLC, leaf width 1 cm, Varian Millennium 

120-leaf MLC, leaf width 0.5 cm for 40 central leaves and 1 cm leaf width 

outside this range and BrainLab micro-MLC, leaf width 0.3 cm for 14 central 

leaves and further out on each side 3 leaves of 0.45 cm and then 3 leaves 

of 0.55 cm. The BrainLab MLC is accessible for a 10 cm field and the Varian 

MLCs for a 40 cm field. Three diagnoses are studied; left sided breast 

cancer, lung cancer and prostate cancer with six patients of each diagnose. 

Planning criterion for the breast patients were that heart should be blocked 

so that the middle point of a MLC leaf edge coincides with the boundary of 

the heart and that 90% of the PTV should be covered by the 93% isodose. 

For the lung cases the 95% isodose should cover 95% of the PTV and for the 

prostate patients the 95% isodose should cover the whole PTV. All treatment 

plans were normalised to a central point in the PTV. Evaluation was done with 

respect to both target coverage and sparing of normal tissues. 

Results: Due to the limitations of the field size the BrainLab MLC could only 

be used for the prostate and for small lung tumours (three patients). In those 

cases, EDWs were used which means that the direction of the leaves are 

locked and furthermore due to a regular and convex shape of the PTVs the 

central leaves became of minor importance. Since the leaves are broader 

than 0.3 cm in the outskirts of the fields there were no significant benefits 

of using this MLC. The breast and lung patients showed consistently a small 

improvement for 0.5 cm versus 1 cm leaf width. The improvements were 

somewhat larger for the large lung tumour patients where the differences in 

mean lung doses were around 1 Gy. The corresponding improvements for 

the prostate cases were small or insignificant. 

Conclusions: In this study the BrainLab MLC could not significantly improve 

the treatment plans for target volumes or healthy tissues. A larger field size 

of smaller MLC leaf widths is required to make benefits from a micro-MLC in 

3DCRT. The improvements of using 0.5 cm compared to 1 cm leaf width were 

small but, in comparison, somewhat larger for the large lung tumour patients. 

1526 poster 

IN OUR OWN WORDS ? THE CANCER JOURNEY; MEETING THE 

CULTURAL NEEDS OF DIVERSE GROUPS 

S. Boyko 1 , M. Hoar 1 , C. McCollom 1 

1 REGIONAL CANCER PROGRAM, Oncology, Sudbury, Canada 

Purpose: To be effective, it is imperative that patient information and education 

meets the learning needs of the individual. Northeastern Ontario is 

populated by people of European descent who speak English and/or French 

as well as indigenous people (First Nations and Ms) who speak a variety of 

languages. Analysis of aboriginal cancer statistics, reinforced by anecdotal 

evidence from aboriginal health care workers, indicate that aboriginal people 

are more likely to be diagnosed later, are less likely to understand conventional 

treatment and therefore more likely to refuse or to comply with any 

conventional treatment offered, resulting in poorer outcomes. Data indicate 

that rates of cancer in aboriginal people in Canada are increasing. 

Materials: During aboriginal relationship development training in 2005 sponsored 

by the Aboriginal Cancer Care Unit of Cancer Care Ontario, cancer 

program staff and aboriginal community partners discussed ways to improve 

aboriginal peoples’ knowledge about the cancer system and increase the likelihood 

that aboriginal people with cancer will choose conventional treatment. 

A steering committee comprised of members from the local regional cancer 

program, aboriginal health care professionals and community agencies 

formed to create a video for, and by, aboriginal people that would demystify 

the cancer experience. 

Results: Using the voices of Aboriginal cancer survivors and their family 

members, the video seeks to increase individual and community access to 

wholistic cancer information, promote screening as a form of prevention and 

to encourage Aboriginal people to seek early treatment. The video will also 

help to educate health care staff of mainstream institutions on the Aboriginal 

worldview of cancer management. The committee obtained government and 

community organizational funding for the video which was completed and 

launched in March 2008. 

Conclusions: Formal evaluation of the video by the public and the healthcare 

professionals who work with aboriginal people is now underway. This presentation 

describes both the development and the pre-release evaluation of the 

video, processes which are grounded in respect for the aboriginal culture and 

support the aboriginal people who shared their stories. 

1527 poster 

INFLUENCE OF CONTRAST MEDIUM ON DOSE CALCULATION IN 

PLANNING OF RADIOTHERAPY FOR LUNG CANCER PATIENTS. 

W. Sapru 1 , D. E. Nygaard 1 , J. Medin 1 



Purpose: At the radiotherapy department of Rigshosptalet, Copenhagen, 

RTT 

S 485 

lung cancer patients are routinely scanned on a Siemens multi-slice CTscanner, 

and dose plans are calculated based on these scans. Before scanning, 

the patients are given an injection of 75 mg Optiray contrast medium 

with an iodine concentration of 300 mg/ml to enhance the blood vessels during 

scanning. However, the contrast medium increases the Hounsfield Units 

on the scans. The aim is to study the impact of the contrast medium on 

the Hounsfield Units and consequently calculation of absorbed dose to the 

spinal cord and the target volume, when administering radiotherapy to these 

patients. 

Materials: Several lung cancer patients treated at the radiotherapy department 

of Rigshosptalet will be included in the study. During scanning, the 

patients are laid supine on the flat tabletop in a Vacfix pillow used for immobilisation 

as for radiotherapy treatment. Markers for the isocenter are placed 

on the patients. After the scan the data is sent to the Varian Eclipse station 

where the radiologist and oncologist define the area of treatment. To 

estimate the contrast distortion, the changes in the Hounsfield units will be 

recorded and changed to a water equivalent. This would mean that the heart, 

aorta and surrounding blood vessels were drawn as regions of interest, and 

allotted a water equivalent density. Plans with and without density correction 

for the Hounsfield Units will be evaluated and compared. The plans will be 

calculated using the single pencil beam algorithm as well as AAA. 

Results: Preliminary results using the single pencil beam algorithm show a 

change in dose volume histograms when comparing plans with and without 

density correction for the Hounsfield Units. After correction an increase of 

spinal cord dose of up to 1.2 Gy could be observed. An increase in target 

volume doses could be observed according to the anatomical position of the 

tumour. 

Conclusions: 

1528 poster 

INFLUENCE OF PROSTATE DISPLACEMENTS FOR REAL DOSE 

DISTRIBUTION IN PROSTATE DURING FRACTIONATED IRRADIA- 

TION FOR CRT AND IMRT 

I. Wesolowska 1 , H. Urbanczyk 2 , L. Misztal 1 , L. Hawrylewicz 1 , W. 

Majewski 2 , J. Ciechowicz 3 , K. Slosarek 1 , L. Miszczyk 2 

1 MSC MEMORIAL CANCER CENTRE & INSTITUTE OF ONCOLOGY, GLIWICE 

BRANCH, Radiotherapy and Brachyterapy Planning Dep., Gliwice, Poland 

2 MSC MEMORIAL CANCER CENTRE & INSTITUTE OF ONCOLOGY, GLIWICE 

BRANCH, Radiotherapy Dep., Gliwice, Poland 

3 MEDICAL UNIVERSITY OF LODZ, Computer Laboratory, Lodz, Poland 

Purpose: To check the influence of the prostate large displacements for a 

real dose distribution in the prostate during fractionated irradiation delivered 

as Conformal Radiotherapy (CRT) or Intensive Modulated (IMRT). 

Materials: The study was based on 40 CT scans series for 5 non advanced 

prostate cancers patients treated with the radical radiotherapy with the largest 

measured prostate displacement, chosen from group of 40 patients. Thermoplastic 

Orfit masks and Orfit HP System Leg and Foot Support were used. 

The PTVs included prostate with a margin (10 mm in posterior and 15 mm in 

other directions). All patients were treated using high energy photons. The 

total dose was 74 Gy, delivered in 37 fractions, 5 times a week. Patients 

were treated conformally, but we prepared several CRT and IMRT plans and 

choose the best CRT and the best IMRT plans for this study. The positions of 

prostate were evaluated once a week using CT scans. CTs, all planning procedures 

and irradiation were performed using the same positioning system. 

Next we overlaped earlier prepared CRT and IMRT plans to all CT scan series 

in relation to the bones and measured dose for different points of prostate 

and made DVH for all plans. Finally we compared difference between dose 

from prepared CRT and IMRT plans and dose measured in CT scans made 

during irradiation. All procedures were performed by the same experienced 

radiation oncologist and three radiation technologists. 

Results: The lowest prostate doses from the treatment plans and calculated 

from control CT scans are shown in the Table I. The medium of minimum 

doses of the all calculation for the all patients were 97,3 % for CRT and 94,7 

% for IMRT. 

Conclusions: Underdosage is larger for IMRT than CRT. Prostate displacements 

could decrease dose in the prostate to an unacceptable level. The 

prostate positions should be checked during irradiation especially for IMRT. 

1529 poster 

MARGINS FOR INTERNAL TARGET VOLUME IN STEREOTACTIC 

RADIOTHERAPY OF THE LUNG 

T. Steyn 1 , Y. Kalidien 1 , A. Petoukhova 1 , J. van Egmond 1 , M. Mast 1 , P. 

van de Vaart 1 

1 MEDICAL CENTRE HAAGLANDEN, Radiotherapy, The Hague, Netherlands

S 486 RTT 

Purpose: Stereotactic radiotherapy (SRT) can cure inoperable patients with 

stage IA/B NSCLC. Hypofractionated SRT enables a high-precision delivery 

of dose biologically equivalent to ≥ 100Gy in only 3-8 fractions. We investigated 

the differences in size and location of the tumour during the period of 

SRT. 

Materials: Patients were positioned on a vacuum cushion and 5 bodymarkers 

were placed on the thorax. A single slice CT-scan was used for targeting 

purposes. During the scan no breathing instructions were given. To make 

sure the total tumour mobility was visible on the CT-scan, several scans were 

made. Firstly, a scan was made of the whole thorax. Then 6 scans were 

made around the tumour area. The Internal Target Volume was contoured 

on all 7 scans (ITV1). ITV1-PTV margins were 5mm in lateral-medial/ventraldorsal 

direction and 6mm in cranial-caudal direction. Additionally, a PTV with 

a margin of 3mm (PTV3mm) in all directions was derived, this PTV was not for 

clinical use. During the study 11 patients were treated on the Novalis machine 

and received a second CT-scan after the second radiation session, for which 

we used the same procedure as we did for the first scan. After contouring 

ITV2 on the second scan, we determined whether the ITV had increased 

or decreased. Usually, an increase can be expected due to oedema. The 

conformity index (CI), the ratio between intersection and union, was used to 

quantify the similarity between the different volumes. A CI of 1 would be best. 

We also compared both ITV’s in absolute values. Finally the coverage of ITV2 

by both PTV’s (5 and 3mm) was calculated. 

Results: Our results show in most cases a slight increase in the ITV but occasionally 

a reduction. The calculations which were performed to determine the 

differences in ITV and margins are: - We found a CI of 0.68. - Although ITV1 

and ITV2 weren’t completely similar, the coverage of ITV2 by PTV5mm was 

still between 96% and 100%. - Decreasing the margins (ITV1- PTV) to 3mm 

in all directions shows less coverage of the ITV2 by PTV3mm (88%-99%). 

Conclusions: We concluded that the target volume coverage was not adequate 

using an ITV-PTV margin of 3mm; we, therefore, use a margin of 5 

mm. The intra- and interobserver variability in delineating the ITV is another 

relevant subject and will be analysed by our group. 

1530 poster 

NURSES OPEN WARD FOR PATIENTS RECEIVING RADIATION 

TREATMENT TO THE HEAD-NECK AREA 

H. Göransson 1 , J. Engberg 1 

1 LUND UNIVERSITY HOSPITAL, Department of Oncology, Lund, Sweden 

Purpose: At the unit for radiation treatment at the University hospital in Lund 

approximately 100 patients are treated for head-neck cancer each year. The 

acute secondary effects that arises after 10-12 treatments and thereafter persist 

for weeks after the treatment is completed demands a lot of resources 

from both nurses and physicians. A diagnostic group for head-neck tumor 

was created during the spring of 2006 and contained 7 oncology nurses and 

2 physicians. The oncology nurses of the team partly works as treatment 

staff on accelerators, CT and at the oncology open wards. One of the aims 

with the group was to start a nurse open ward for patients during the first 

2-3 weeks of their ongoing radiation treatment. Earlier the patients went to 

visit with a physician once a week during the entire radiation treatment. The 

purpose of the nurse open ward is to create continuity, to improve nursing 

care, to prevent and to ease the secondary effects of the radiation treatment. 

This means that doctor‘s appointments are disengaged and consequently the 

physician can become more available to acute patients. 

Materials: The nursing open ward was started autumn 2006 with approximately 

2-7 patients a week. The nurse takes anamnesis on distress/diet, 

weight and inspects the oral cavity and the skin in the treated area which is 

rated according to RTOG and palpation of the lymph node in the neck. If 

necessary prescriptions on linctus paracetamol, tablet paracetamol, linctus 

nystatin and ointment hydrocortisone can be given to the patient. 

Results: After completed treatment the patient have answer a questionnaire 

regarding information on treatment and the secondary effects, which pointed 

towards satisfied patients. The result of the questionnaire is the basis for a 

checklist that has been used by nurses at the first arrival talk at the radiation 

department and can also be used as auxiliary means at the nurse open ward. 

The staff has also answered a questionnaire regarding the nurse open ward. 

It has not yet been completed but both nurses and physicians seems satisfied. 

The nurses think that their jobs has become more interesting and competence 

increasing and the physicians claim they now have more time to take care of 

more qualified patient care. 

Conclusions: The nurse open ward is under development and our vision for 

the future is to give patients the possibility of telephone contact and consulting 

even after completed radiation treatment which can increase continuity and 

security for the patient and thereby in the future reduce acute doctor‘s call. 

1531 poster 

ONE-YEAR EXPERIENCE WITH INTRAOPERATIVE ADAPTIVE 

BRACHYTHERAPY OF PROSTATE IMPLANTS USING C-ARM CONE 

BEAM CT 

R. Kattevilder 1 , J. Immerzeel 1 , C. Hoekstra 1 , R. Westendorp 1 , A. Minken 

1 , A. van t Riet 1 

1 RISO, Deventer, Netherlands 

Purpose: 1. To introduce a time-efficient procedure to optimize prostate implants 

in the Operating Room by transrectal ultrasound (TRUS) and C-arm 

Cone Beam CT (CBCT) feedback and 2. to demonstrate the necessity of this 

procedure by evaluating a group of 213 patients. 

Materials: The implant-procedure is performed in the OR, having available 

a planning system, TRUS-equipment and a 3D C-arm fluoroscopic unit with 

isocentric design, used to generate C-arm CBCT images. The patient is under 

spinal anesthesia based on a one day admission. The procedure starts 

with the implantation of four fiducial gold markers at anatomically relevant 

positions. Next the prostate is implanted using TRUS-guided real-time planning. 

Consecutively the contours of prostate and urethra are delineated on 

a post-implant TRUS study with 2,5 mm thick slices and a CBCT is made 

(with the legs lowered and the US-probe removed from the rectum). With the 

implanted gold markers as a reference, post-implant TRUS and C-arm CBCT 

are co-registered, the implant is critically analysed and examined for dose 

deficiencies. In case the radiation-oncologist meets critical areas with underdosage, 

an adaptive-plan is made, in which seeds are added to optimise the 

dosimetry. Additional seeds are inserted, finishing the procedure. A second 

C-arm CBCT is performed and registered with the post-implant TRUS-study 

to document the final day 0 dosimetry. Dosimetric quality is assessed by comparing 

D90 and V100 of the uncorrected and corrected groups at day 0 and 

30. 

Results: In 2007 213 patients have been implanted at our institute using 

this adaptive method. In 55 (26%) of the patients a critical underdosage was 

observed. On average 3,7 seeds were added. On day 0, in the adapted 

group the mean D90 increased 10%, for the V100 this increase was 9%. On 

day 30 the dosimetry values were adequate and comparable for both groups, 

indicating effective adaptation of underdosed prostate implants. 

Conclusions: It is necessary to perform dosimetry immediately after implantation 

and, in case of critical underdosage, to correct this by adding remedial 

seeds in the same procedure. The use of a C-arm CBCT in the OR makes 

this feasible in a time-efficient manner. 

1532 poster 

RADIOSURGERY QUALITY ASSURANCE WITH EPID IMAGES 

I. Cardoso 1 , I. Cardoso 1 , C. Marcelino 1 , M. Pontes 1 , A. Coutinho 1 , S. 

Lopes 1 , M. Barreiros 1 , V. Santos 1 , L. Moreno 1 , P. Carvoeiras 1 

1 CENTRO ONCOLÓGICO DR A NATÁLIA CHAVES, Lisboa, Portugal 

Purpose: Any quality assurance program in Radiosurgery has as major goal 

the verification of mechanical, geometric and radiation parameters. Usually 

the last of these parameters are measured with radiographic film, witch generates 

a major drawback in terms of time of exposure, processing and scanning, 

and also in the costs involved. In this work we propose a new EPID based 

procedure that improves the factors referred previously and guarantees the 

same level of accuracy has radiographic film. 

Materials: Winston-Lutz, collimator star shot and light field coincidence tests 

were made on a Clinac 2100CD (Varian R○) with a M3 micromultileaf collimator 

(Brainlab R○), and on a Trilogy (Varian R○). Both of these accelerators 

are equipped with aS1000 electronic portal image devices, with a detector 

resolution of 1024x768 pixels. Portal images were acquired in the integrated 

image mode. Simultaneously films were placed above the cassette, and were 

scanned on VIDAR VXR-16 DosimetryPro R○for latter comparison. The analysis 

of the results was performed on RIT113 R○. 

Results: The results of the analysis of the portal images were compared 

to those performed with films. Collimator star shot test achieved comparable 

results for EPID and films: the average difference was 0.05 mm. In the 

Winston-Lutz test, the average difference was around 0.14 mm with a standard 

deviation of 0.10 mm. 

Conclusions: The use of an EPID system in a quality assurance program 

gives a reasonable and efficient alternative to the use of films, reducing both 

time and cost.

1533 poster 

RATIONALE FOR IMPLEMENTATION OF 3D VERIFICATION FOR 

IMRT IN HEAD AND NECK - DETERMINATION OF THE RELIABILITY 

OF 2D VS 3D VERIFICATION METHODS 

M. Rolfo 1 , M. Wada 1 , R. Height 1 , E. Zupan 1 , M. Handley 1 , N. Anderson 

1 

1 AUSTIN HEALTH RADIATION ONCOLOGY CENTRE, Melbourne, Australia 

Purpose: The clinical consequences of minor set up variations in IMRT of 

head and neck cancer is increasingly apparent. Residual errors and interobserver 

variations are key factors in the consideration of treatment verification 

programs. In order to justify the clinical implementation of 3D verification 

methods, we designed a study to examine the discrepancy of daily set up error, 

as determined by manual 2D Mv EPI verification using a "template match" 

method against an automated 3D "bony match" method using data acquired 

from the Elekta Synergy TM Cone Beam CT (CBCT) equipped Linear Accelerator. 

Materials: Daily EPI and CBCT’s were acquired from five patients undergoing 

IMRT for curative H&N cancer. The 2D EPI images were assessed off-line by 

four experienced Radiation Therapists using the Elekta iView. The EPI based 

shift data from all participants was analysed in order to determine the interobserver 

variation. CBCT data was analysed using the "clip box" process 

using an automated bony match registration process. For each given fraction, 

EPI and CBCT data sets shared the same treatment isocentre and the relative 

shifts and mean residual errors were determined. For the purpose of this 

study, the automated 3D process was designated as the gold standard in 

determining the set up error. Data will be presented showing the residual error 

associated with a 2D bony match process when compared with an automated 

3D process. 

Results: Taking account of the inter-observer variations in the 2D daily 

shift determination process, the mean residual error inherent in the 2D process 

when contrasted with a automated 3D process was -0.11cm (95% 

CI -0.41cm/+0.19cm), -0.21cm (95% CI 0.39/-0.03) & -0.10cm (95% CI 

0.28/+0.08) in the left/right, anterior/posterior and superior/inferior planes. 

Whilst the magnitude of the residual error could be considered to be small 

and relatively insignificant in the clinical context, the 95% CI shows significant 

inter-observer variation, leading to inappropriate interventions that may have 

an adverse impact on clinical outcomes in the high dose IMRT paradigm. 

Conclusions: In the context of IMRT plans with high dose gradients adjacent 

to critical structures and targets, reduction of residual error is important in 

ensuring the delivery of planned dose. The range of observer interpretation 

of 2D images as seen by the 95% CI, indicates that the 2D process may be 

unreliable for head and neck IMRT. At the Austin the decision was made to 

implement a clinical protocol utilizing 3D data and the automated matching 

process for positional verification in patients undergoing IMRT in head and 

neck cancers. 

1534 poster 

REDUCTION OF BOOST CLINICAL TARGET VOLUME AND DIS- 

PLACEMENT OF BOOST LOCALIZATION FOLLOWING REPEATED 

CT SCANNING FOR EARLY STAGE BREAST CARCINOMA; A 

SINGLE INSTITUTION EXPERIENCE. 

T. Baarda 1 , H. Tabak 1 , Y. van der Linden 1 

1 RADIOTHERAPEUTIC INSTITUTE FRIESLAND, Leeuwarden, Netherlands 

Purpose: In institutions without waiting time for start of radiation treatment 

after initial breast conserving surgery, patients may show large hematomas in 

their surgical cavity on the planning CT scan. When delineation and planning 

of the boost clinical target volume (CTV) is performed on the initial CT scan 

and subsequent shrinkage of the cavity and displacement of the surgical clips 

is ignored, large treatment fields and possible geographical miss may occur. 

Second CT scanning after 4 weeks of radiotherapy may well be advisory in 

these patients. 

Materials: In 15 consecutive patients who were referred for postoperative radiotherapy 

after breast conserving surgery, a second CT scan 4 weeks after 

the initial localization CT scan was made. All patients received 50 Gy in 25 

fractions to the whole breast followed by a boost of 16-20 Gy to the lumpectomy 

cavity (LC). The following targets were delineated on both CT scans 

conform the EORTC Boost/No Boost study: the LC, plus a margin of 15 mm 

for CTV, with correction for skin and pectoral muscle. A descriptive analysis 

was performed of time intervals and reduction of lumpectomy volumes in 

cm3 and in percentages. Breast contouring and boost CTV were matched on 

the initial and second CT, and movement of LC and the surgical clips were 

analyzed. 

Results: Mean time from surgery was 19 days (range 12-38), and mean time 

from initial to second CT was 32 days (range 23-42). Mean reduction of LC 

was 50 cm3 (range 1-118 cm3), mean percentage LC volume reduction was 

60% (range 13-89%). Mean reduction of CTV was 102 cm3 (range 7-230 

cm3), mean percentage CTV reduction was 40% (range 9-72%) (figure 1). 

Changes of the breast were considerable, and shrinkage of the boost cavity 

was not concentric, but eccentric (figure 2). 

Conclusions: Reduction of boost volume and altered localization of the sur- 

RTT 

S 487 

gical cavity after repeated CT scanning were considerable in patients with 

minimal waiting time (< 20 days) between breast conserving surgery and 

start of radiation. A second CT scan to delineate the boost CTV should be 

standard practice in patients with short waiting times after breast conserving 

surgery. 

1535 poster 

START OF THE STEREOTACTIC RADIOSURGERY IN SLOVENIA 

N. Bizjak 1 , M. Jerneja 1 , V. Ilija 1 

1 INSTITUTE OF ONCOLOGY LJUBLJANA, Department of Radiotherapy, 


Purpose: The incidence of cancer patients is increasing in Slovenia. Considering 

that we have only one radiotherapy centre, we started with modernization 

and enlargement in year 2002. In years from 2002 to 2006 we installed 

a Philips CT scanner MX 8000, a linear accelerator Varian Clinac 2100C/D 

with the optional use of conical collimators and attachable mMLC m3.All the 

necessary stereotactic equipment as well as the treatment planning system 

was installed by the manufacturer BrainLab Company. 

Materials: The first beginning of stereotactic radiosurgery in Slovenia goes 

in year 1999 (April 26th). The whole equipment for stereotactic radiosurgery 

was constructed at the Institute for Electronic and Vacuum Technique in cooperation 

with Institute of Oncology department for radiotherapy. On linear 

accelerator SL75/5 we treated the first patient with a solitary metastasis in 

one fraction of total dose 25 Gy.After 8 years in year 2007 we restarted with 

stereotactic radiosurgery. From June to December 2007 we treated 4 patients. 

One of them had a solitary metastasis in the brain while the other 3 

had each 2 metastasis. In all cases the patient’s head was fixed with 4 carbon 

pins in the stereotactic head ring. After the mount of the head ring, a CT scan 

was performed using a localization box with a Z-shaped fiducial rods for the 

determination of local coordinate system. Prior to the CT scan a MR scan 

was performed for the outline of the patient’s structures used for planning. 

All patients were treated on linear accelerator (Varian Clinac 2100C/D) dedicated 

for SRS. Treatment plan consisted of five non-coplanar dynamic arc 

beams using the conical collimators smaller than 2cm. A total dose of 25 Gy 

was given to the planning target volume. In February 2008 we had a patient 

whose MR scan showed 2 metastasis, one of them having an irregular shape 

and bigger size. For this reason we had to use the mMLC m3 to form the 

shape of the beams. A head ring was used to fix the patient and an axial CT 

scan was performed. For each PTV five conformal arc beams were planned 

with a total dose of 20 Gy per PTV 

Results: From 1999 to February 2008 we have treated 6 patients with one 

or two metastasis in the brain. Two of them had hypernefroma metastasis; 

two patients were with metastasis of breasts cancer and two patients with 

metastasis of lung cancer. The patient treated in 1999 is still alive while from 

the other five patients just one died because of the bad prognosis. 

Conclusions: During the years from 2000 to 2006 an enlargement and modernization 

of Radiotherapy department was carried out. The modernization 

opened new future possibilities to implement new methods and techniques in 

SRS as well as in SRT. The total successful SRS treatments in the past year 

at our department risen up to 5 treated patients. The plan for this year is to 

begin with fractionated stereotactic radiotherapy treatment. 

1536 poster 

STRATEGIES FOR CREATING A SUPPORTING SOCIAL CLIMATE 

ON THE RADIATION ONCOLOGY WARD 

M. Wysmans 1 , M. Van de Wiele 1 , D. Van den Weyngaert 2 

1 MAIA FOUNDATION, Training department, Rotterdam, Netherlands 

2 MIDDELHEIM ACADEMIC HOSPITAL, Radiation Oncology, Antwerp, Belgium 

Purpose: Radiation oncology wards in Belgium have experienced rapid 

growth in the number of patients and treatments over the last few years. This 

places great strain on the staff, especially in view of the restricted possibilities

S 488 SOCIAL, STRUCTURAL, LOGISTICS AND OTHER ASPECTS OF RO : EDUCATION AND TRAINING 

for recruitment of new doctors, nurses and physicists. Coupled with the typically 

restricted spatial working conditions, this can lead to decreasing work 

satisfaction, conflicts within and between professional groups and generally 

negative effects on the social climate. Ultimately this may lead to increased 

personnel turnover and below capacity functioning of the ward. It may also 

affect the way the ward climate is perceived by patients. How can staff care 

for patients if their own needs are not met? In order to prevent this downward 

spiral from occurring, the management of the radiation oncology ward of the 

Middelheim Academic Hospital in Antwerp has chosen to initiate a program 

of care for the caregivers. 

Materials: Together with external trainers strategies were developed for safeguarding 

the social climate on the ward. These included - coaching sessions 

with the medical and nursing leadership - individual interviews and separate 

focus groups with nursing, medical and physicist staff aimed at determining 

areas of perceived dysfunction and dissatisfaction and - working sessions 

in which key problems were tackled and bottom up solutions were devised. 

Workshops concerning such issues as handling difficult feelings, working with 

conflict and communication skills were offered. An organizational change process 

was initiated, in order to ensure adequate implementation of these solutions. 

Work with the different disciplines focused on empowering each discipline, 

transcending within group conflicts and developing a renewed sense of 

common purpose. The process of vision development was characterized by 

a joint bottom up and top down approach. At a later stage, the process will 

aim at the generation of a shared multidisciplinary understanding regarding 

the care to be provided, supported by all three professional subgroups and 

management. 

Results: Preliminary results show a more harmonious working climate, more 

supportive social relations, more openness and mutual respect, less indirect 

communication patterns and an apparently reduced risk of personnel 

turnover. 

Conclusions: Work on a radiation oncology ward can be stressful and generate 

a less than optimal working climate. Interventions on a ward of a Belgian 

academic hospital show that it is possible to turn this downward spiral around 

and to generate a more supportive social environment. 

1537 poster 

THE MAIN CHALLENGES FOR RADIATION TECHNICIANS IN THE 

PROCESS OF RADIOTHERAPY 

D. Radola 1 , K. Toklowicz 1 , A. Musielak 1 , K. Olejniczak 1 

1 WIELKOPOLSKIE CENTRUM ONKOLOGII, Poznañ, Poland 

Purpose: 

Materials: In our center we use the following methods:I Control of 

documentation- radiation technicians are responsible for checking all computer 

calculation and correct entry in patients’ cards; it is authorized with 

their own signature.II Dosimetry in vivo- dosimetry process is used to verify 

the dose in every treatment planning- in basic standard radiation technician 

has to measure the dose twice or once in every stage of treatment.III Portal 

images- images are created by every treatment machine at the begining of 

the treatment - portal images are made not less often then every seven days 

and on every change of treatment planIV Portal dosimetry 

Results: Thanks to portal image verification we can check patient’s position 

and eliminate errors - if they occur. Using the in-vivo dosimetry we confirm 

the concordance of the prescribed dose with the dose delivered. 

Conclusions: Using mentioned activities helps to increase the quality of 

treatment and makes the procedures more comfortable for patients. 

1538 poster 

THE PALLIATIVE IRRADIATION OF RENAL CANCER BONE METAS- 

TASES 

K. Szczepanik 1 , H. Urbanczyk 1 , J. Ciechowicz 2 , B. Jochymek 1 , L. 

Miszczyk 1 

1 MSC MEMORIAL CANCER CENTRE & INSTITUTE ONCOLOGY GLIWICE 

BRANCH, Radiotherapy Dep., Gliwice, Poland 

2 MEDICAL UNIVERSITY OF LODZ, Computer Laboratory, Lodz, Poland 

Purpose: To evaluate the most often location of renal cancer bone metastases 

and an evaluation of their irradiation results. 

Materials: The study is based on 39 patients (12 female and 27 male), aged 

from 26 to 77 (mean 59), with 73 focus of bone metastases. Performance 

status (Zubrod scale) were 0 four patients, 1 sixteen patients, 2 eleven patients 

and 3 five patients. Patients had been irradiated since 2004 to 2006, 

using 6 MV or 20MV photon beams. The single dose of 8 Gy was delivered. 

Radiotherapy effects were evaluated in three levels pain scale: pain 

relief, stabilisation or pain increase. McNemary test was used for statistical 

analysis. 

Results: The most often locations of renal cancer bone metastases are lumbar 

vertebras (24 focuses [32,9%]) and pelvis bones (17 focuses [23,3%]). 

Five patients (12,8 %) have pain increase after irradiation, eighteen patients 

(46,2 %) have pain stabilisation and sixteen patients (41 %) have pain relief. 

There are not statistically significant correlations between localisation of 

bone metastases, performance status and treatment’s result. Fourteen patients 

(35,9%) were still in follow-up one year after treatment. Twelve of those 

fourteen had pain relief after treatment and two of them had pain stabilisation. 

We find statistically significant correlation between radiotherapy effect 

and observed survival (p=0.0005). 

Conclusions: Renal cancer bone metastases are most often localized in 

lumbar vertebras and pelvis bones. Radiotherapy single fraction 8 Gy is good 

option for patients. Patients with better treatment result could have longer 

survival. 

Social, structural, logistics and 

other aspects of RO : Education 

and training 

1539 poster 

AN ALGORITHM USED IN RADIATION THERAPY VENIPUNCTURE 

CERTIFICATION 

K. Jensen 1 , Y. Bayliss 1 

1 TOM BAKER CANCER CENTER, Radiation Therapy, Calgary, Alberta, 

Canada 

Purpose: In 2006, the administrators of the Radiation Treatment Program 

(RTP) at the Tom Baker Cancer Center (TBCC) mandated that a Radiation 

Therapist venipuncture certification process be developed and implemented 

while continuing to provide the highest patient care and maintaining high efficiency 

operations. 

Materials: The authors of the venipuncture certification process designed an 

educational algorithm tool and collaborated with provincial licensing organizations 

and with the disciplines of Radiography and Nursing to create a unique 

competency based venipuncture certification process for Radiation Therapists. 

The paper and/or presentation describes the individual components of 

the algorithm design, summarizes the details of the collaborative agreement 

between the Radiation Treatment Program and the Alberta College of Medical 

Diagnostic & Therapeutic Technologists and provides details of the impact 

this process has had on departmental operations and access to service for 

patients. 

Results: In 2007 Radiation Therapists successfully completed the RTP 

Venipuncture Certification Program and were licensed to perform venipuncture. 

As of February 2008, 255 venipuncture procedures have been performed 

by licensed Radiation Therapists in Alberta, Canada. 

Conclusions: The RTP Radiation Therapy Venipuncture Certification Program 

has been implemented using an algoritm as a tool for design, and is a 

design which when examined clearly illistrates the advantages of following a 

structured form with as little ambiguity as possible. 

1540 poster 

ANALYSIS OF DEMOGRAPHY, QUALITY OF TRAINING AND MOTI- 

VATIONS OF RESIDENTS IN RADIATION ONCOLOGY TRAINING 

PERIOD IN FRANCE 

Y. Pointreau 1 , S. Dewas 2 , S. Rivera 3 , P. Blanchard 4 , C. Vautravers 3 , V. 

Marchand 5 , C. Lafond 6 , J. J. Mazeron 7 , G. Kantor 8 

1 CHU BRETONNEAU CENTRE H.S.KAPLAN, Radiotherapy, Tours, France 

2 CENTRE OSCAR LAMBRET, Radiotherapy, Lille, France 

3 CENTRE G F LECLERC, Radiotherapy, Dijon, France 


5 CENTRE RENÉ GAUDUCHEAU, Radiotherapy, Nantes, France 

6 CENTRE ALEXIS VAUTRIN, Radiotherapy, Vandoeuvre-lès-Nancy, France 

7 PITIÉ SALPÉTRIÈRE, Radiotherapy, Paris, France 

8 CENTRE BERGONIÉ, Radiotherapy, Bordeaux, France 

Purpose: Although a recent increase in number of young radiation oncologists 

in training was observed during the past decade, the general demographic 

evolution of radiation oncologists remains a problem for health authorities. 

Materials: During the seven past national annual courses which were organised 

and supported by the Young French Society of Radiation Oncology 

(SFjRO), the French Society of Radiation Oncology (SFRO), the National College 

of Cancerology (CNEC) and the French National Cancer Institute (INCa), 

different types of surveys were realized in order to analyse demography, quality 

of training and motivations of French residents in radiation oncology. The 

latest results were collected during the last national course, which took place 

in March 2008. Seventy-five out of hundred-ten participants of young French 

radiation oncologists ("DES internes des hopitaux" or residents) attended the 

national course and 72 questionnaires were analysed. 

Results: Since 2002, the total number of residents increased regularly (50, 

75, 103, 115 residents respectively in 2000, 2005, 2007 and 2008). Men

SOCIAL, STRUCTURAL, LOGISTICS AND OTHER ASPECTS OF RO : EDUCATION AND TRAINING 

and women are presently 48.5% and 51.5% respectively. Qualitative analysis 

of practical and theoretical training was performed using a visual analogical 

scale from zero to ten. Scores of 5.6 and 6.1 were respectively observed. 

Others descriptions of local training in the different universities (as clinical 

skills, clinical cases analysis, bibliography session&) are described. Finally, 

analysis of motivations for the choice of the radiation oncology speciality 

demonstrates common interests in both medical practice and technical aspects 

in oncology. Innovations, technology, imaging, research are also widely 

mentioned. Fifteen residents will finish their training by the end of 2008, 32 

are expected in 2009 and 33 in 2010. Almost all residents believe that a 

post-graduate position is necessary to complete their training as assistant 

professor ("chefs de clinique assistants des hpitaux") in university hospital or 

cancer centre. Unfortunately, only 33 assistant professors positions are available 

in France representing half of the need. Only twenty-one residents out of 

hundred-four have already a position of assistant professor. The availability 

of such position remains unsure for the rest of them. 

Conclusions: i/ Despite recent increase in number of resident in radiation oncology 

in France, health authorities still in great need to create new positions 

of assistant professors to avoid demographic crisis. ii/ Since 2002, establishment 

of SFjRO facilitated national links between residents, between residents 

and professors (CNEC), and between national French society (SFRO) and 

European society (ESTRO). 

1541 poster 

EVOLUTION OF THE CONTENT AND OBJECTIVE OF THE UNIVER- 

SITY COURSE FOR RADIATION TECHNICIANS 

J. Malicki 1 

1 1. GREAT POLAND CANCER CENTRE, 2. UNIVERSITY OF MEDICAL 

SCIENCES, Electroradiology, Poznan, Poland 

Purpose: To show the changes in curriculum for radiation technicians in 

bachelor and master courses at Poznan University of Medical Sciences and 

the process of defining graduates skills and competences 

Materials: Bachelor course on radiation techniques started in Poznan in 

2001. First graduates will receive master degree this year. The content of 

the curriculum referred to ETSTRO endorsed curricula but was supplemented 

with issues linked with diagnostic radiology and nuclear medicine. In the period 

since 2001 two phases can be seen. The initial idea was to divide the 

content of overall 5 year programme in a way that bachelor course provided 

skills and the license to employment in hospitals in the department of radiotherapy, 

diagnostics radiology and nuclear medicine. In principle the recipients 

of bachelor diplomas should in extended time replace technicians who 

graduated from non-university schools (NUS). The new regulation prepared 

by the Parliament, effective 2009 enumerates jobs in health sector. It constitutes 

the requirements for bachelor studies in radiation techniques, approves 

diploma issued by NUS in the transitional period but does not mention the 

master courses in this discipline. 

Results: At the time of launching the university course, technicians were 

toughed at NUS, at which 2 years programme comprised over 1700 hours of 

teaching. To avoid legal constraints during first years, the university admitted 

only holders of the NUS diplomas, thus the practical training was shortened, 

assuming that students possessed the practical skills already. The spearing 

time slots were used to teach the subjects associated with public health 

organisation, which enabled students to continue the study at master programmes 

in public health specialty, which was appreciated. Beginning the 

2005 the University admitted students who did not have the diplomas from 

NUS. It enforced the extension of the practical training but in consequence 

eliminated classes associated with public health, thus ceased an opportunity 

to continue study at master programmes of public health, due to insufficient 

background. The obvious reason for impossible coexistence of two specialties 

within one course became contested by the students, those who wanted 

to combine bachelor study in radiation techniques with a master degree from 

public health. The curriculum of master course was reoriented in order to provide 

specific knowledge from biomedical science, engineering and physics. 

This new master course underwent debate, whether it was necessary and 

what competences the graduates would obtain. The higher staff qualification 

did not justify the course enough, because degree holders would expect new 

responsibilities and clearly indicated tasks in hospitals teams, different from 

those, which technicians with bachelor diploma got. To solve the constraint 

an agreement between all parties had to be achieved. At the Poznan Medical 

University and Cancer Centre a compromise has been set between radiologists, 

radiation oncologists, physicists, and technicians leading to the two 

lists of competences after master and bachelor courses. The only way to go 

forward was to establish at the university so called "unique course" as the 

consensus on national level regarding competencies needs more years. 

Conclusions: It is still debatable how to divide the 5 years (3+2) university 

course from the point of skills, competences, license to work and knowledge. 

The development in technology and biomedicine however precluded combining 

the radiation techniques and public health in one course, as these two 

specialties differed too much. 

1542 poster 

S 489 

INFORMATION MEETINGS FOR PATIENTS WITH PROSTATE CAN- 

CER AND THEIR PARTNERS PRIOR TO COMBINED TREATMEN 

K. Sjodin 1 , M. Gustavsson 1 , A. M. Stenberg 1 , A. Wigren 1 , L. Sharp 1 

1 KAROLINSKA UNIVERSITY HOSPITAL, Oncology/Radiotherapy, Stockholm, 

Sweden 

Purpose: Adequate information and eduacation is essential for patientes 

with cancer and their partners to be able to participate in decition-making 

regarding cancer treatment and care. All patientes with prostatecancer at 

our department have individual appointments with an oncologist and a cancer 

nurse prior to their combined treatment with external beam radiation and 

HDR brachy therapy, but many patients still describe a lack of necessary information. 

Even if information meetings in groups are common in cancer centers 

today, there are little consistent research showing the usefulness of these 

activities for patients with prostate cancer and their partners.The purpose of 

this study is to explore if information meetings in groups (as a complement 

to individual appointments with oncologist and cancer nurse) could improve 

the information and education for patients receiving combined treatment with 

external beam radiation and HDR brachy herapy. 

Materials: Prior to the initiation of the information meetings, we collected 

anonymous questionnaires from 20 patients with prostate cancer, regarding 

their information and education needs prior to cancer treatment. The collected 

data inspired the content of the information meetings. Several group 

meeting were held, with approximately four patients and their partners participating 

at each meeting. The meetings was organised and lead by specialist 

trained cancer nurses. 

Results: Data collection is ongoing and will be discussed at this presentation. 

Data is collected from repeated anonymous questionnaires from patients who 

have participated in the group meeting and will then be compared with data 

collected prior to the initiation of the group meetings. 

Conclusions: 

1543 poster 

LEARNING FROM PATIENTS - INNOVATION OF THE CURRICULUM 

TO MEET THE PSYCHOSOCIAL NEEDS OF CANCER PATIENTS. 

K. Williamson 1 

1 CARDIFF UNIVERSITY, Department of radiography, Cardiff, Wales, United 

Kingdom 

Purpose: Representative professional bodies in the UK have established 

specific guidelines for higher education providers on curriculum content in 

order that emerging graduates are equipped with the knowledge and skills 

required to meet the needs of their patients within an ever changing healthcare 

environment. (SCoR, 2003). For therapeutic radiography, a key professional 

standard relates to the integration of theory with practice to ensure the 

physical and psychosocial well-being of patients with cancer (SCoR, 2003, 

p.13). Aim: The development of learning strategies for undergraduate student 

therapeutic radiographers to enable better understanding of the psychosocial 

needs of cancer patients undergoing radiotherapy treatment. 

Materials: Final year BSc (Hons) Radiotherapy and Oncology students at 

Cardiff University were introduced to the concepts and theories related to the 

physical, social and psychological care of patients. They were then tasked 

with composing and justifying a series of questions which were put to a panel 

of volunteer cancer survivors and patient carers.After the question and answer 

session, students reflected on the process, aligning their personal experiences 

with the defined learning outcomes of the module and described how 

this would facilitate better understanding of their patients’ needs and consequently 

development of their professional practice. 

Results: Student reflections and evaluations reported positive outcomes 

from the learning activity. All students involved reported that the activity was 

beneficial to their education in terms of meeting the learning outcomes for 

this component of the curriculum. Issues raised by cancer surivors were acknowledged, 

with students stating an intention to change practice as a consequence 

of this new knowledge. The biggest impact on understanding was 

seen to be in relation to the needs of patient carers.; ’I never give the carer a 

thought. In fact I don’t think many radiographers do!’. 

Conclusions: As graduate healthcare professionals, therapeutic radiographers 

must be equipped with the skills for autonomous practice, probity 

and empathy with the needs of the cancer patient. Education providers are 

obliged to teach these skills and the curricula of higher education institutions 

should reflect this. This example demonstrates how through the engagement 

of service users, the academic learning environment can innovate the curriculum, 

developing strategies to provide the future cancer workforce with the 

skills required for the development of professional practice and improvement 

of service provision.

S 490 SOCIAL, STRUCTURAL, LOGISTICS AND OTHER ASPECTS OF RO : OTHERS 

1544 poster 

RADIATION ONCOLOGY TRAINING IN POLAND: RESULTS OF A 

NATIONAL SURVEY (2007). 

M. Niemiec 1 , L. Kêpka 1 , B. Maciejewski 2 , B. Lindner 1 , K. Bujko 1 

1 M. SKLODOWSKA-CURIE MEMORIAL CANCER CENTER AND INSTITUTE OF 

ONCOLOGY, Department of Radiation Oncology, Warsaw, Poland 


INSTITUTE OF ONCOLOGY GLIWICE, Department of Radiation Oncology, 


Purpose: The aim of this survey is to evaluate quality of training in radiation 

oncology in Poland in relation to the ESTRO recommendations, and to learn 

motivation, level of satisfaction, suggestions and career plans of radiation 

oncologists. 

Materials: The detailed questionnaire was addressed to radiation oncologists 

from all centres in Poland who have been certified as specialists after 1990. 

Results: Among 212, 103 radiation oncologists (49%) responded to the 

questionnaire . 40% of the respondents claimed that the majority of teachers/supervisors 

devoted sufficient time to their training (60% in academic, 

28% in regional centres); 60% had access to the literature, and 50% to the 

internet. Number of treated patients during training period was on average 

450, however it ranged between centres from 10 to 3000. 69% of the respondents 

had an out-door training (median duration - 2 months), 21% in abroad 

centres. 55% attended international courses/conferences. Respondents from 

academic centres had an access and attended national or international training 

more often than those from regional centres. Financial matters as a major 

obstacle for an out-door training have been mentioned by 93% of the respondents. 

64 % of the respondents were pleased/somewhat pleased with general 

quality of the training , and the remaining 36% were unsatisfied (mainly in regional 

centres). Considering career plans, 72% respondents want to continue 

practice in home-institution, however 24% have declared to leave Poland and 

to continue radiotherapy practice abroad. 

Conclusions: This first national survey has shown some weak points in radiotherapy 

training in Poland, mainly quality differences between departments 

in favour of academic centres. Some of the problems can and should be 

solved by the Polish Society for Radiation Oncology, others need legislation 

changes and decisions at the level of Mininstry of Health. 

1545 poster 

SHARING KNOWLEDGE AND EXPERIENCE DURING THE INTRO- 

DUCTION OF IMRT 

M. Zijp 1 , B. Mijnheer 1 , I. Bruinvis 1 

1 INHOLLAND UNIVERSITY OF APPLIED SCIENCES, Department of Medical 

Technology in Oncology, Haarlem, Netherlands 

Purpose: Intensity-Modulated Radiotherapy (IMRT) is currently being introduced 

into many radiotherapy departments. Using this sophisticated technique 

is raising concern among RT professionals about introducing (undetected) 

errors. This anxiety may disappear when professionals are aware of 

the way IMRT is implemented in other hospitals. For this purpose the project: 

’Advanced Radiotherapy: accurate and safe’ was initiated to transfer knowledge 

about all practical aspects concerning IMRT between professionals. Ultimately 

this project should result in general applicable recommendations on 

how to implement IMRT in starting institutions. 

Materials: The project is a cooperation between INHOLLAND University of 

Applied Sciences and five RT departments in the Netherlands (VUmc, AMC 

and NKI-AVL in Amsterdam, MCA in Alkmaar and UMCU in Utrecht). The 

project is performed in four closely related task groups, each consisting of 

participants from all five RT departments and the university. Each group focuses 

on a specific aspect of IMRT: inverse treatment planning, quality assurance, 

overall implementation procedures and image-guidance. Within every 

group several practical and scientific questions are posed that will allow professionals 

to share their experience with IMRT. 

Results: RTTs performed a pilot study on treatment planning and quality 

assurance as part of their training, and presented their results. In the task 

groups detailed questionnaires were filled in, followed by site visits to get 

a complete view of the IMRT practice. Site-specific and general problems 

were identified. E.g. planning possibilities are dependent on the type of TPS 

while methods for quality control vary due to planning and delivery system 

differences. Besides this, protocols can also be different. The origins of 

these differences are now being analyzed in order to develop a general model 

for IMRT implementation. Also the extent of IMRT implementation was very 

much dependent on infrastructure (availability of personnel, time). The participants 

in this project are very enthusiastic to provide information on their 

department, share their experience and learn from each other. 

Conclusions: RT departments have their own methods, procedures, protocols 

and equipment which makes the introduction of IMRT unique in each 

institution. Exchange of knowledge about motivation behind solved problems 

or specific choices are of great importance to guarantee the safe introduction 

of IMRT. 


other aspects of RO : Others 

1546 poster 

AN INVESTIGATIONAL ANALYSIS FOR CORRELATION OF CANCER 

PATIENTS RECEIVING WESTERN,CHINESE AND ALTERNATIVE 

MEDICAL TREATMENTS 

C. Yu-Ping 1 

1 CHANG GUNG MEMORIAL HOSPITAL, Dept. of Radiation Oncology, 

Kaohsiung Hsien, Chinese Taipei 

Purpose: This study included irradiated cancer patients to explore multivariate 

correlation factors and current status among Western (WM) Chinese (CM) 

and Alternative (AM) medical treatment modalities so that one can understand 

the magnitude of tabooed food and predictors for receiving alternative 

treatment. From cultural view points , medical staff should try to investigate 

motivation of herb and alternative modalities of treatment, enhancing communication 

& instruction to patients to accept most updated medical knowledge 

which may yield a synergistic effect to traditional orthodoxic medicineC 

Materials: Between August 1, 2005 and September 30, 2005, 338 cancer 

patients irradiated at the department of radiation oncology (RT dept.) Chang 

Gung Memorial Hospital were retrospectively reviewed with respect to patients’ 

data collected from self-structured questionnaire assisted by nursing 

staff of the dept. All cases came from different area islandwide and should 

have completed a full course of RT with a minimum follow-up period of three 

years. 

Results: Data revealed that the first choice of cancer treatment was WM followed 

by at least 1 to 2 kind of CM or AM which accounted for 156(46.1%) 

patients. Of these, 108(32%) patients took mainly herb drugs as a major part 

of treatment by CM. The duration of most adjuvant treatment was approximately 

3 months at an expense of around NT$100000.00. Two hundred and 

twenty nine (67.8%) cases considered CM or AM having potential for cure of 

cancer and the information regarding to these type of treatment was mainly 

from patients’ family 194(57.4%) or relatives 175(51.8%).Dietary concept of 

the majority 207(61.2%) cases originated from patients or their relatives and 

friends. The numbers of tabooed food has been increased for 138(40.8%) 

patients prior to cancer attack up to 261(77.2%) patients after a diagnosis 

of malignancy. In cases that patients should pay medical expense by themselves, 

153(45%) would like to receive WM while 138(41%) would choose a 

combined treatment with CM plus WM. 

Conclusions: Different age groups yield no significant correlation to the selection 

of either CM or WM (p > 0.05); Although different educational backgrounds 

had no specific impact in the choice of CM (p > 0.05) yet effect 

significantly in the selection of various types of AM (p < 0.011). Patients 

with educational background equalled to or above college level may predominantly 

choose a physiologic type of AM (p

SOCIAL, STRUCTURAL, LOGISTICS AND OTHER ASPECTS OF RO : RISK AND QUALITY MANAGEMENT 

tation of IMRT in community centers is often insurmountable. University of 

Pittsburgh Cancer Institute (UPCI) established a centralized, advanced planning 

service in Pittsburgh (D3- www.d3radiationplanning.com) to make IMRT 

widely available in its community cancer centers throughout Western Pennsylvania. 

In January 2007, Beacon Hospital (Dublin, Ireland) established a 

transatlantic hub-and-spoke relationship with the UPCI to implement IMRT in 

our centre. This is an initial analysis of that experience. 

Materials: The initial 3 weeks of implementation were dedicated to assess 

equipment compatibility and on-site local staff training. UPCI clinical guidelines 

were adapted for PTV/OAR definition, prescription doses and dosevolume 

constraints(DVC). After planning CT, delineation of PTV/OAR was 

performed by the local physician and this data was transferred to D3 using 

an FTP link. IMRT planning was performed at D3 advanced planning facility 

in Pittsburgh, by specialized dosimetrists and physicists. A web-based protocol 

was used for interaction between the US planner and the local team, 

regarding dose prescription, contours acceptance and plan completion. Interactive 

conferences were used for problematic cases and for initial tutoring. 

Once completed, the IMRT plan was exported back to the Beacon, where the 

local team reviewed and approved plans. Comprehensive local QA measurements 

were performed prior to treatment.Eighty patients were treated with 

IMRT and we report the experience with the 60 prostate patients. 

Results: All plans were complex, involving multiple-phase treatment. Of 60 

submitted cases with prostate cancer: 2 had bilateral hip prosthesis, 5 had 

small/large bowel within/near PTV’s and 2 required irradiation of para-aortic 

nodes. For these patients, web-based consultation with a D3 physicist ensured 

agreement of contouring, dose prescriptions, and DVC. The median 

FTP transfer time was 20 min. In 5% of the cases initial transfer was unsuccessful. 

Re-submission of the entire dataset was necessary. The median 

time to finalize IMRT planning (by D3) was 3.73 days (1-15days). Only 5 patients 

were re-planned because of revised OAR’s, revised constraints, or new 

treatment position. Rigorous QA was performed for all patients to ensure the 

integrity of exported data set and imported IMRT plan. 

Conclusions: Transatlantic hub-and-spoke networking is feasible. Clinical 

and technical protocols developed in a US-based NCI-designated Comprehensive 

Cancer Centre have been implemented in a small centre in another 

country, both for systematic aspects and individual patient care. Each individual 

patient availed of centralized design expertise.This is a model for national 

and international devolution of new sophisticated radiation treatment technology. 

1548 poster 

SMOKING CESSATION PROGRAM FOR PATIENTS REFERRED FOR 

RADIATION THERAPY WITH CURATIVE INTENT 

C. Jansen 1 , E. Gitsels 1 , P. Poortmans 1 , B. Oei 1 , M. van de Pol 1 

1 DR BERNARD VERBEETEN INSTITUUT, Tilburg, Netherlands 

Purpose: Continued tobacco use following cancer diagnosis increases the 

risk of relapse and diminishes treatment efficacy. As a consequence, smoking 

abstinence following diagnosis of lung and head and neck cancer increases 

overall survival. Therefore, patients should be stimulated to quit smoking 

definitively. To support this, a smoking cessation program for patients referred 

for a curative radiation treatment of especially but not exclusively these 

cancers was launched. We hereby describe the first results of this program. 

Materials: Patients who are current smokers at referral for radiotherapy for 

lung, head and neck and bladder cancer are offered to participate to the 

smoking cessation program. Smoking patients with other cancers are informed 

and stimulated to participate as well. The cornerstone of this program 

is constituted of counselling and intensive support. The use of nicotine replacement 

therapy is advised whenever deemed necessary. In exceptional 

cases bupropion is prescribed. 

Results: In the first 2 years, 112 patients entered the smoking cessation program. 

The median follow-up time is 4.5 months. Thirty-eight patients (34%) 

had primary lung cancer, 23 patients (21%) had head and neck cancer and 

23 patients (21%) had breast cancer. The median number of pack-years in 

this patient group was 42.5 years (range 10-141) and the median number of 

daily cigarette consumption was 20 (range 5-75). Seventy-five patients succeeded 

to quit. The smoking free survival rate at 6 and at 12 months of those 

patients is 71% and 68%, respectively and of the total group who entered the 

program 50 and 48%, respectively. Of the 37 patients who did not succeed 

to quit and of the 20 patients who restarted smoking after initial cessation, 

the majority (65% and 65 % respectively) decreased tobacco consumption 

significantly (at least 50% reduction of their initial consumption). The primary 

tumour, number of cigarettes per day and number of pack-years did not influence 

the cessation rate, nor the smoking free survival rate at 6 months. 

Conclusions: The structured smoking cessation strategy in our radiotherapy 

department resulted in a high and lasting cessation rate, irrespective of the 

primary tumour and the smoking behaviour at the entrance of the program. 

S 491 


other aspects of RO : Risk and 

quality management 

1549 poster 

DEVELOPMENT AND EVALUATION OF A METHOD TO VERIFY 

THE INTEGRITY OF TREATMENT DATA THROUGHOUT THE 

RADIOTHERAPY PROCESS 

F. Nordström 1 , H. Gustavsson 1 , C. Ceberg 2 , O. Holmberg 3 , L. Wittgren 

4 , P. Björk 5 , S. Johansson 6 , S. Bäck 1 

1 

MALMÖ UNIVERSITY HOSPITAL, Medical Radiation Physics, Lund 

University, Malmö, Sweden 

2 

LUND UNIVERSITY HOSPITAL, Department of Radiation Physics, Lund, 

Sweden 

3 


Division of Radiophysics, Herlev, Denmark 

4 

MALMÖ UNIVERSITY HOSPITAL, Medical Radiation Physics, Malmö, 

Sweden 

5 

MÄLAR HOSPITAL, Department of Medical Physics and Bioengineering, 

Eskilstuna, Sweden 

6 

COUNTY HOSPITAL KALMAR, Department of Radiation Physics, Kalmar, 

Sweden 

Purpose: The transfer of treatment parameters between different systems 

during the radiotherapy (RT) process could potentially introduce discrepancies 

between datasets. Today DICOM-RT has been widely accepted and has 

a major role in the communication between different RT systems. Undoubtedly 

the absence of manual transfer ensures a higher level of data integrity. 

However, manual input might be difficult to avoid at some steps of the treatment 

chain, which inevitably leads to an increased risk. This study aims to 

develop a method to compare DICOM-RT Plans from different steps of the 

treatment chain in order to verify the integrity of datasets. The feasibility of 

the method has also been evaluated. 

Materials: An in-house developed software for independent monitor unit verification 

(Radiotherapy Verification Program/RVP) was functionally expanded 

to incorporate a plan parameter comparison utility. A retrospective analysis of 

96 treatment plans was undertaken, including both 3D-CRT and IMRT plans. 

The approved plan generated with the treatment planning system (TPS, MasterPlan, 

Nucletron) was compared with the treated plan as registered in the 

record and verify system (RV, Visir, Nucletron). Both plans were exported 

to RVP as DICOM-RT Plan objects. The parameters of importance for the 

treatment outcome and patient safety were identified and compared. The 

rounding towards nearest integer in the RV was taken into account by using 

a tolerance level. 

Results: Fifteen DICOM-RT related parameters were identified to be of importance 

for the treatment outcome (Table). The multi-leaf collimator (MLC) 

positions outside the collimator opening are handled differently in the RV 

compared to the TPS, which leads to compromised integrity. However, the 

treatment unit behavior is the same. This is also the case for the wedge 

information. This was taken into account in the RVP comparison, by not comparing 

control point data by control point data. Instead, the corresponding 

treatment unit setting in each control point was compared. From the set of 

important parameters, six types of deviations were observed. Investigations 

of the deviations concluded that some methodology in clinical routine could 

be associated with an increased risk of errors. For instance, reading of table 

position during the first treatment in the course caused the table angle discrepancies. 

A misplacement during this treatment could therefore lead to the 

whole course being delivered with erroneous parameters.

S 492 SOCIAL, STRUCTURAL, LOGISTICS AND OTHER ASPECTS OF RO : RISK AND QUALITY MANAGEMENT 

Conclusions: The proposed method can be used to verify the integrity of 

datasets in radiotherapy. This increases the safety for the individual patient 

by ensuring that the intended treatment is delivered. Hazard analysis of the 

discovered discrepancies can be utilized to identify safety critical procedures 

and systematic deviations that are associated with an increased risk. 

1550 poster 

EXPERIENCE WITH THE PHYSICS ORDERFORM IN A RADIO- 

THERAPY NETWORK 

M. Melchor 1 , D. Martínez 1 , F. Candela 1 , M. Soler 2 

1 HOSPITAL DE LA RIBERA, Radiation Physics, Alzira - Valencia, Spain 

2 HOSPITAL DE LA RIBERA, Radiotherapy, Alzira - Valencia, Spain 

Purpose: To manage, to control and to optimize the interaction between the 

radiophysicist and the radiotherapist in the planning process, as well as having 

an easier access to the patient’s data for everyone involved in the radiotherapy 

procedure, with the goal of becoming paperless. 

Materials: The Hospital has acquired a network where an interface for a 

better communication between radiophysicists and radiotherapists has been 

customized to behave as it is mentioned in the specific Spanish law. Data 

from patients, follow ups, nursery consultations and treatments are kept in 

a single database, with specific access from several places for every group 

of users Besides, it has been developed the "Physics orderform", which consists 

of a interface where staff from Radiation Physics department and from 

Radiotherapy department send messages. There has been defined several 

steps in a patient’s treatment planning, and personal which must complete 

every step. Once every step is completed the person who does it signs the 

message (there is a set of predefined messages) which was coming from the 

person who made the previous step and then sends a new message to the 

person which must do the next step. Everyone has a kind of mailbox where 

is possible to query and manage his/her messages. The complete network 

has three modules, treatment module, which is also accessible for physicians 

and physicists (where everyone checks the final treatment parameters) and a 

scheduler, where everyone handles his/her appointments and where every- 

one can set appointments with the resources and personal of the mentioned 

departments. The main use of the scheduler is to assign priority in time for 

the planning of the patients. In fact, treatment’s beginning time is assigned 

also in the patient’s folder, but scheduler allows to set a kind of appointment 

which includes priority. Every result of the planning work, not only plans, but 

also histograms, isodose images, DRRs, is stored in this patient’s folder. 

Results: Thanks to the controls on this process (every message, every sign, 

is stored on a database, where every message is stored, even erased ones) 

it has been possible to detect messages which are active for a long time, and 

to detect "Physics orderforms" which have not a correct ending message, to 

ensure the accomplishment of the whole process in every patient. The main 

result we got was the time that is spent in every part of the process, and this 

way of working helped to detect flaw points and optimize the workflow.The 

experience during the first year of use will be presented. 

Conclusions: The interface which has been described before has improved 

the workflow in the planning process, has helped to detect the most lasting 

steps in the planning process and to correct them. It also helped to manage 

the information and to have a best access to it, contributing to create a 

paperless environment which is being encouraged by the hospital. 

1551 poster 

GAPS IN RADIATION TREATMENTS, ANALYSIS OF CAUSES AND 

ITS COMPENSATIONS 

M. I. Algara López 1 , J. Quera Jordana 1 , S. Caballero Delpozo 1 , R. 

Jimenez Lahuerta 1 , N. Rodriguez de Dios 2 , P. Foro Arnalot 1 , A. M. Reig 

Castillejo 1 , I. Membrive Conejo 1 , J. Lozano Galan 1 , E. Fernández-Velilla 

1 , M. Lacruz Bassols 1 , X. Sanz Latiesas 1 

1 HOSPITAL DE LA ESPERANZA-IMAS, Radiation Therapy, Barcelona, Spain 

2 HOSPITAL DE LA ESPERANZA, Radiation Therapy, Barcelona, Spain 

Purpose: Treatment interruptions due to toxicities or machine breakdowns 

diminish efficacy of radiation therapy. We intended to know the amount of 

interruptions and develop correcting measures inside our quality control program. 

Materials: In our department, two accelerators work uninterruptedly during 

13 hours daily. During the year 2007 a total of 1336 treatments were performed, 

of whom 1213 consisted in more than one session and were included 

in our analysis. Treatment interruptions were detected by in-house 

software and grouped according their causes: toxicities, machine breakdown, 

scheduled interruptions for machine service, patient-related or other. Also 

treatments were classified as not interrupted, interrupted less than 5 days or 

interrupted equal or more than 5 days. Different correction methods were 

employed. 

Results: During study time, 2937 sessions were not performed (9% of total). 

Causes of interruption were: toxicities 67 (2.3%), machine breakdown 1520 

(51.7%), scheduled interruptions 955 (32.5%), patient-related 230 (7.8%) and 

others 165 (5.62%). In 29.7 % of patients were no interruptions, 49.2% were 

interrupted inferior to 5 days, and 21.5% equal to 5 or more days. If interruption 

was only 1 to 4 days, no compensation was made. Between 5-7 

days, supplemental dose in last session was performed. In patients with interruption 

of 8 or more sessions, appropriate number of sessions was add if 

corresponding physician found it necessary. 

Conclusions: The majority of interruptions are related to treatments units. 

So, the appropriate measure is to fit out a supplemental machine. In its 

absence, correction measures can be undertaken by dose adjustments or 

compensations as adopted in our study.

SOCIAL, STRUCTURAL, LOGISTICS AND OTHER ASPECTS OF RO : RISK AND QUALITY MANAGEMENT 

1552 poster 

IMPLEMENTATION OF A QUALITY ASSURANCE PROGRAM FOR 

COMPUTERIZED TREATMENT PLANNING SYSTEMS 

F. Ribeiro 1 , S. Macedo 1 , M. Oliveira 1 , A. Oliveira 1 , O. Santos 1 , C. Simão 

1 , M. Roldão 1 , J. Faria 1 

1 INSTITUTE PORTUGUESE OF ONCOLOGY, FRANCISCO GENTIL, Radiother- 

apy, Lisbon, Portugal 

Purpose: The administration of a course of radiotherapy requires a whole 

series of steps going from basic dosimetry over tumour localization, treatment 

planning, dose calculation, to patient immobilization. Each of the many steps 

in radiation therapy contributes to the total uncertainties in the absorbed dose 

delivered to the patients. The treatment planning system (TPS) has become a 

key element in the radiotherapy process with the introduction of new images 

techniques based 3D conformal treatment planning. For patient safety and 

success of treatment, the accurate and stable functioning of the TPS is of the 

highest importance. The objective of this paper is to present our experience 

in the implementation of a quality assurance program of Precise Plan (vs R 

2.15) treatment planning system. 

Materials: The purpose of this quality control (QC) program is to ensure that 

operational standards for TPS, that were considered acceptable at time of 

purchase, continue to be maintained as closely as possible. The necessary 

tests to implement this quality assurance program were established and performed, 

in accordance with the IAEA publication TRS430 and with AAPM 

Task Group 53. A number of non-dosimetric tests, including digitizer accuracy, 

image acquisition and display, and hardcopy output, is presented. Dosimetric 

tests include verification of monitor units (MU’s), standard isodoses, 

and clinical cases. 

Results: The program tested accuracy and constancy through several hardware 

and software upgrades to our TPS. These tests are outlined for the 

Precise Plan TPS but can be generalized to any TPS currently in use. All the 

results of the reproducibility tests are inside of considered tolerance interval. 

Conclusions: The results indicate that the accuracy of the Precise Plan system 

are inside of range proposed by TRS430 and with Task Group 53. 

1553 poster 

ORGANIZATIONAL, TECHNICAL, PHYSICAL AND CLINICAL QUAL- 

ITY STANDARDS FOR RADIOTHERAPY. 

M. Bogusz 1 , J. Malicki 2 , A. Roszak 3 , P. Martenka 4 

1 WIELKOPOLSKIE CANCER CENTRE, Quality Management, Poznan, Poland 

2 WIELKOPOLSKIE CANCER CENTRE, Medical Physics , Poznan, Poland 

3 WIELKOPOLSKIE CANCER CENTRE, Department of Radiotherapy and 

Oncological Gynaecology , Poznan, Poland 

4 WIELKOPOLSKIE CANCER CENTRE, Radiation Oncology, Poznan, Poland 

Purpose: Indisputably radiotherapy has become an entirely interdisciplinary 

specialty. This situation requires efficient planning, verification, monitoring, 

quality control and constant improvement of all aspects of service delivery, 

referring both to patients’ (including diagnosis, prescription and method of 

treatment, its justification, realization and follow up) and organizational, technical 

and physical matters. The aim of this work was to develop technical, 

physical and clinical quality standards for radiotherapy. 

Materials: For the development of quality standards the comparison analysis 

of EU and Polish acts of law passed between 1980 and 2006 was conducted, 

the universal industrial ISO norm 9001:2000 referring to quality management 

system was reviewed. Recommendations of this norm were completed with 

detailed quality standards based on the work experience of authors, and 

the review of articles on quality assurance and quality control standards for 

radiotherapy published between 1984 and 2008 and the review of current 

recommendations and guidelines of American, International, European and 

National bodies (associations, societies, agencies such as AAPM, ESTRO, 

IAEA, OECI) for QA in radiotherapy. 

Results: As a result 352 quality standards for radiotherapy were developed 

and categorized into the following three groups: 1) organizational standards 

2/ physical and technical standards and 3/ clinical standards. Organizational 

standards were divided into following sub-categories: 1.1 Politics and management 

1.2 Documentation 1.2.1. Documentation of Quality management 

System 1.2.2. Records and logs 1.2.3. Registries (incl. cancer registry) 1.3. 

Resources 1.3.1. Human resources 1.3.2 Infrastructure, facilities and equipment 

1.3.3. Environment 1.3.3.1. Radiation protection 1.4. Interdisciplinary 

approach Physical and technical standards were divided into the following 

sub-categories: 2.1. Specification of products 2.2. Quality assurance 2.2.1. 

Physical, technical, mechanical and geometrical parameters control of: therapeutic 

machines, imaging systems (CT, PET), simulators, treatment planning 

systems, radiotherapy management systems 2.2.1. Quality control of gauges 

and control equipment and tools 2.3. Documentation and records 2.4. Physical 

parameters 2.5. Malfunctions 2.6. Improvement 2.6.1. Equipment audit 

2.6.2. Dosimetrical audit Clinical standards were divided into the following 

sub-categories: 3.1. Patient’s referral/ treatment prescription 3.2. Therapeutic 

protocol 3.3. Interdisciplinary approach 3.4. Communication 3.5. Treatment 

planning 3.6. Verification of treatment planning 3.7. Conduction of treatment 

3.8. Verification of treatment 3.9. Treatment termination/cancellation 

S 493 

3.10. Radiological incidents and accidents 3.11. Quality control of treatment 

3.12. Reference levels of radiation doses 3.13. Documentation and records 

3.14. Follow-up 3.15. Clinical audits 

Conclusions: Proposed quality standards for radiotherapy, can be used by 

any institution using ionizing radiation for medical procedures. Nevertheless 

standards are only of value if they are implemented, reviewed, audited and 

improved and if there is a clear mechanism in place to monitor and address 

failure to meet agreed standards. 

1554 poster 

PILOT STUDY ON ELABORATING STANDARDS IN THE INTERNAL 

CLINICAL AUDIT OF RADIOTHERAPY -WIELKOPOLSKIE CANCER 

CENTER EXPERIENCE. 

P. Martenka 1 , J. Malicki 2 , M. Bogusz 3 

1 

WCO, Radiotherapy, Poznan, Poland 

2 

WCO, Physics, Poznan, Poland 

3 

WCO, Quality Management, Poznan, Poland 

Purpose: Elaboration of selected standards in the internal clinical audit of 

radiotherapy and validation of the model in the Wielkopolskie Cancer Center. 

Materials: Methodology of standard elaboration includes the following steps: 

1)defining standards by authors, based on the review of the literature and 

current recommendations and guidelines of American, International, European 

and National bodies such as AAPM, ESTRO, IAEA, OECI for QA in 

radiotherapy 2)institutional cost-effectiveness analysis, modification and final 

consensual approval of the standard by the group of local Wielkopolskie Cancer 

Center administrators ,economists and staff representatives involved in 

the radiotherapy treatment 3) performance of baseline internal clinical audit 

which will give feedback concerning possible shortcomings of audit methodology 

and information on baseline status of institution 4)in the future regular 

performance of clinical radiotherapy audits based on developed standards is 

planned with the aim to improve the quality of medical care in Wielkopolskie 

Cancer Center 

Results: The European Medical Exposure Directive (MED) 97/43/Euratom 

since May 2001 has become fundamental legislation for Member States. In 

accordance with the Directive, Polish Ordinance of the Ministry of Health from 

2002 obliges every Radiotherapy Center to perform the external and internal 

clinical audits of radiotherapy as a part of its quality control programs. However, 

detailed regulations concerning clinical standards to which the auditor 

could refer as well as the scope of the audit has not yet been elaborated nor 

passed. In this study standards regarding clinical issues such as completeness 

of medical records, toxicity monitoring system, imaging modalities used 

in treatment planning , presence of site specific institutional treatment protocols, 

maximum quantity of workload per staff and other has been defined and 

baseline audit has been performed. 

Conclusions: Elaboration of the institutional standards for clinical internal 

audits is a cornerstone of successful quality control program and a prerequisite 

for fruitful performance of clinical audit. Such procedure should be 

performed in every radiotherapy center and elaboration of the institutional 

standards should be based on international and national guidelines and recommendations. 

1555 poster 

RADIATION-ONCOLOGY IN A SANDBOX 

M. Heuser 1 , G. Lutters 1 , S. Bodis 1 

1 KANTONSSPITAL AARAU, Department of Radiation Oncology, Aarau, 

Switzerland 

Purpose: Software solutions are crucial to structure the workflow in 

Radiation-Oncology. Pre-testing of new or updated components is nearly 

impossible. One exception could be a virtual replica of the institutional IT 

landscape. We present a virtual Radiation Oncology IT-testsystem ("sandbox") 

where all our new or updated components can be pre-tested. 

Materials: We use the virtualization suite by VMWare on WIN XP. The original 

software SIEMENS COHERENCE Oncologist, Physicist and LANTIS have 

been cloned on the original Work Station (WS) and encapsulated into so 

called images. The Sandbox runs the images on virtual Work Stations (vWS). 

The vWS are connected by a virtual switch. 

Results: The vWS works in all functions like the real system. Only the imaging 

performance shows a slight degradation, which can be explained by the 

extra overhead caused by the second operating system. DICOM RT communication 

between the vWS can be configured and run like a real system. 

Corrupted systems can be restored by reloading the image onto the vWS. 

Conclusions: Virtualization using cloned medical software is a feasible strategy 

to create a sandbox. These vWS can be tested without compromising 

the productive environment or patient data. vWS can ease maintenance and 

increase uptime. Therefore manufacturers should be encouraged to licence 

their software for virtual machines.

S 494 SOCIAL, STRUCTURAL, LOGISTICS AND OTHER ASPECTS OF RO : RISK AND QUALITY MANAGEMENT 

1556 poster 

TOWARDS A 100% SECURE QA SYSTEM FOR RT PATIENT TREAT- 

MENT 

E. Franken 1 , H. Akhiat 1 , P. Voet 1 , B. Kanis 1 , B. van der Leije 1 , Y. 

Seppenwoolde 1 , M. Dirkx 1 , B. Heijmen 1 

1 ERASMUS MC - DANIEL DEN HOED CANCER CLINIC, Radiotherapy, 


Purpose: Currently, a quality assurance (QA) system for external beam radiotherapy 

treatment (EBRT) is implemented in our clinic, which aims at a 

100% guarantee that the treatment is delivered according to the plan that 

was prescribed and approved by the physician. To achieve this, retro- and 

prospective checks on the treatment plans being delivered are performed 

daily. 

Materials: A key element of the developed QA system is a standalone patient 

database with a complete description of each treatment plan, the so-called 

Definitive Treatment Prescription (DTP). It comprises a digital treatment prescription 

as approved by the physician, patient set-up information, reference 

to the CT scan used for planning, the DRRs, 3D dose distribution, beam setup, 

fractionation schedule and digital signatures of the physician, physicist, 

technicians and plan review board who approved the plan. In the RT workflow, 

three go/no go tests are built in, based on required subsets of digital signatures 

gathered in the DTP. Only if all relevant signatures are present, (1) the 

treatment parameters can be exported from the TPS, (2) the treatment plan 

can be imported in the treatment record and verify system MOSAIQ (IMPAC 

Medical Systems, Inc.) and (3) actual beam delivery is made possible by setting 

the field approval status in the MOSAIQ database. A second element is a 

comprehensive tool for comparison of the treatment parameters and calendar 

in Mosaiq, with the data in the DTP. Every night, this fully automatic analysis is 

performed, both retrospectively (addressing already delivered fractions) and 

prospectively (based on the scheduled fractions for the next days). The program 

provides a list of all relevant differences in beam definition, fractionation 

and/or delivered patient dose as well as a report of the overrides during patient 

treatment, which can be analysed quickly by a physicist. Furthermore, 

the system features a ’signature withdrawal’ option, in case the patient treatment 

plan should be adapted at any stage in the course of treatment. Then, 

the current plan can no longer be delivered at the treatment unit. 

Results: The QA system provides a valuable overview of the frequency of the 

(mostly minor) errors and near-incidents encountered during the RT patient 

treatment. Any possible deviation from the intended treatment is detected at 

an early stage, facilitating corrective actions before the next treatment fraction. 

Conclusions: The newly introduced QA system is an important step towards 

a 100% guarantee on a faultless patient treatment delivery.

Au t h o r s In d e x

AUTHOR INDEX 

Author index 

Aarup L., 1301 

Abbas T., 955 

Abbeel S., 239 

Abboud B., 725 

Abdulfatah S. B., 253 

Abe T., 619 

Abei M., 710, 721 

Abel E., 801 

Abo-Madyan Y., 94, 1401 

Abolfath R., 1307 

Abraham C., 464 

Abrahamsson E., 58 

Abrahamsson P. A., 113, 157 

Abreu W., 670 

Abtahi M., 1135 

Abusaris H., 1003 

Achour H., 1085 

Ackermann B., 938, 1384 

Acun H., 1246 

Adam J. F., 346 

Adamczyk S., 1220 

Adams L., 305 

Adams S., 510 

Adamska K., 806 

Adamus-Górka M., 226, 1337, 1442 

Adell G., 557 

Adenis A., 691 

Adlard J., 896 

Adrian B., 66 

Aerts H., 118, 256, 306, 463, 914 

af Wetterstedt S., 1417 

Agami R., 495 

Agaoglu F., 1006 

Aghili M., 457, 1409 

Agostino Ninone S., 728 

Agoston P., 1033, 1076 

Aguayo M., 1062 

Aguiló F., 328 

Ahlberg A., 835, 1446 

Ahlgren G., 1043 

Ahlgren J., 361 

Ahlman H., 1468, 1502 

Ahmad R., 547, 1172 

Ahmad S., 866 

Ahmed M., 846 

Ahmed Q., 774, 821 

Ahmed S., 821 

Ahn A., 783 

Ahn G. O., 200 

Ahn P., 783, 850 

Ahn S. D., 707, 1221 

Ahn Y. C., 828 

Ahnesjö A., 103, 163, 224, 343, 860, 887, 

1272, 1381 

Aijun S., 436 

Aird E., 356 

Aitken A., 98, 149, 228, 379, 380, 1139, 1184, 

1421 

Ajlouni M., 92 

Akbulut G., 1457 

Akhiat H., 1556 

Akhlaghpoor S., 1135 

Akins R., 327, 603, 933, 1037, 1038 

Akkus Yildirim B., 1458 

Akman F., 782 

Akselbo L., 957 

Aksu M. G., 578, 709, 858 

Akyol F., 901 

Akyurek S., 922 

Al -Qaisieh B., 1026 

Al kattar Z., 1257 

Al-Abany M., 282, 307, 762, 835, 1444, 1446 

Al-Booz H., 752, 760 

Al-Buhairi M., 1435 

Al-Hadyan K., 1435 

Al-Harbi N., 1435 

Al-Mamgani A., 257 

Al-Qaisieh B., 122, 325, 1289, 1306, 1312 

Al-Rajhi N., 1435 

Alam F., 634, 996 

Alber M., 26, 73, 293, 298, 300, 362, 484, 985, 

1015 

Albers D., 1223, 1237 

Aletti P., 1321 

Alevronta E., 282, 835, 1446 

Alexander E., 1360 

Alexis F., 686 

Alfieri S., 706 

Alfonsi M., 360, 460 

Algara López M., 1105 

Algara López M. I., 1551 

Algara M., 613, 868, 947, 964, 1275, 1509 

Ali M., 774 

Ali S., 1397 

Alidoosti A., 1388 

Allal A. S., 682 

Allison R., 905 

Alm Carlsson G., 1255 

Alongi F., 980, 981, 1008, 1022 

Alonzi R., 3 

Alsadius D., 235, 1130 

Alsbeih G., 1435 

Alsner J., 458, 459 

Alterio D., 793 

Altomare V., 592, 611 

Altorjai G., 664 

Altun M., 786 

Aluwini S., 1011, 1524 

Alvarez A., 1005 

Alves de Oliveira C. C., 1224 

Ambolt P., 1324 

Ameijide A., 747 

Amelio D., 965 

Ameri A., 1388 

Amgarou K., 1245 

Amini Adle M., 958 

Anacak Y., 754, 1410 

Anandadas C., 1027 

Andersen A., 957 

Andersen C., 480 

Andersen C. E., 1254, 1382 

Andersen L., 817 

Anderson H., 235 

Anderson J., 800, 856 

Anderson N., 589, 1533 

Anderson P., 327, 603, 604, 650, 933, 1037, 

1038 

Andersson H., 753 

Andisheh B., 1379 

Andratschke N., 468 

Andreassen B., 77, 1400 

Andreo P., 6 

Andreou C., 999 

Andrich R., 592, 611 

Andræ N., 1272 

Ang K., 424 

Angada L., 1352 

Anglada L., 1353 

Anglesio S., 1452 

Angyalfi S., 995 

Anido Herranz U., 612, 700 

Anile C., 632 

Anne Marie M. A., 1274 

Annunziata A., 422 

Ansell A., 1493 

Anselmo P., 662, 669, 965 

Antal G., 571, 1123 

Antczak A., 1086 

Antinori A., 706 

Antonadou D., 963 

Antonovic L., 1255 

Antoun N., 633 

Antunes T., 659 

Antypas C., 781 

Anyamene N., 705 

Aoyama H., 1161 

Apicella G., 632, 674, 712 

Appleby H., 553 

Appold S., 1178 

Aprile I., 656 

Apte A., 464 

Araki H., 750 

Aras A., 586, 615, 754, 765 

Araujo V., 670 

Araya M., 1083 

Arazi L., 563, 574, 1501 

Arcangeli G., 248, 600, 853, 1029, 1056 

Arcangeli S., 248, 352, 600, 988, 1029, 1056 

Archambault Y., 142 

Aref I., 92 

Arenas M., 580 

Arenas Prat M., 747 

Arends M., 1266 

Ares C., 292 

Arguis M., 255, 646, 672 

Arias F., 811 

Ariga H., 720, 911, 1031 

Aristei C., 965 

Armoogum K., 1241 

Armpilia C., 21, 781 

Armstrong E., 399 

Armstrong J., 539, 1045, 1417, 1547 

Arponen P., 357 

Arrazubi V., 811 

Arruda J., 647, 648, 670 

Arsovski O., 628 

Arteaga de Castro C., 740 

Artola N., 799, 1061, 1340 

Asadpour B., 246 

Ascaso C., 580 

Ash D., 325 

Ashida S., 997 

Ashley S., 228 

Ashok S., 820 

Ashworth A., 353 

Asin G., 811 

Aslay I., 767 

Asplund S., 1392 

Aspradakis M. M., 83 

Assimakopoulos K., 956 

Assis I., 647, 648, 670 

Astner S., 95, 883 

Aström L., 1060 

Atahan L., 1458 

Ataman F., 874 

Athanassios T., 968 

Athanassiou H., 963 

Atkin A., 576 

Atkinson C., 452 

Atsuta T., 694 

Auer G., 810 

Augelli B., 102, 1185 

Aupérin A., 360 

Ausma A. H., 1266 

Autorino R., 777, 1492 

Auñon C., 1352 

Avall-Lundqvist E., 307, 762, 1444 

Avuzzi B., 1054 

Axelsson S., 605 

Ay M. E., 1429 

Ay O. I., 1429 

Ay S., 874 

Ayadi M., 1288 

Ayaz L., 1477 

Azario L., 632, 1185 

Azhar R., 774, 821 

Azma Z., 1277 

Aznar M., 597 

Azoury F., 725 

Azria D., 270 

Azuma H., 1024 

Baarda T., 1534 

Baas M., 350 

Baas-Thijssen M., 962 

Baba F., 921 

Baba M., 863 

Babij D., 92 

Babu Rao P., 1229 

Baccolini M., 454, 1042 

Bachelot T., 958 

Bachtiary B., 739 

Bacia S., 1346, 1365 

Bacon S., 1104 

Baczyk M., 1086 

Badel J. N., 1209 

Baek C. H., 828 

Baerg B., 773 

Bagheri S., 1135 

Bagnoli R., 965 

Bahary J. P., 1047 

Bahl A., 741, 766 

Bahoric B., 1126 

Baier K., 491 

S 495

S 496 AUTHOR INDEX 

Bailey H., 187 

Baiocchi C., 908, 998 

Baiotto B., 1244 

Bajrovic A., 150 

Baker C., 89 

Baker M., 302 

Bakker J., 1311 

Balafouta M., 781 

Balart J., 1426 

Baldissera A., 840, 882, 1121 

Balducci M., 268, 352, 632, 645, 674, 712, 

777, 833, 930, 969, 1070, 1358, 

1492, 1506 

Ballas L., 618 

Ballester F., 120, 125, 565, 1198, 1250, 1282, 

1283, 1341, 1393, 1396 

Balloni H., 566 

Balm A., 275 

Baltalarli B., 765, 922 

Baltas D., 120, 122, 123 

Balter J., 474, 521 

Balteskard L., 273 

Bamberg M., 1015, 1106 

Bambery A., 88 

Bang Y. J., 587, 679 

Banihashemi B., 1487 

Bankowska-Wozniak M., 427 

Bankvall G., 1299 

Bansal V., 809 

Bar Ad V., 735, 778, 790 

Bar Sela G., 954 

Bar-Deroma R., 356, 954, 1410 

Barba M. C., 352 

Barbachano Y., 792, 846 

Barber J., 955 

Barberis M., 1203 

Bardet E., 360, 460, 794, 798, 1231 

Bardiès M., 1270 

Bares R., 1106 

Baricza K., 1476 

Barnes T., 966 

Barnett G., 432, 433 

Barnhoorn J., 96 

Barra S., 950 

Barreiros M., 349, 1532 

Barsingerhorn M., 1397 

Bartelink H., 315, 602, 622 

Bartsch R., 664 

Basagni M. L., 662, 669 

Bashkirov V., 338 

Bassetti C., 640 

Basu S., 570 

Batalla A., 81 

Batel V., 1300 

Batterman J., 1003 

Bauer H. C. F., 1089 

Bauer R., 1413 

Bauer V., 280 

Baugh G., 1206 

Baumann M., 24, 70, 128, 314, 430, 431, 467, 

1178, 1479 

Baumann P., 134, 523 

Baumert B., 253, 297, 665, 865 

Bayley A., 86, 785, 1412 

Bayliss Y., 1539 

Bayman N., 1138 

Baynes C., 432 

Bayouth J., 982 

Bazalova M., 347 

Beadsmoore C., 791, 818 

Beaulieu L., 347, 1279 

Bebb G., 862 

Bebenek M., 631 

Beck R., 468 

Becker J., 1242 

Bedford J., 80, 149, 228 

Beets-Tan R., 245, 269, 306 

Begg A., 15, 428, 492 

Behrendt K., 1436 

Behrens C., 299, 1205, 1219 

Beiki-Ardakani A., 238 

Beisker W., 1431 

Beitsch P., 320 

Bejzak A., 152 

Bel A., 351, 1116, 1142, 1169, 1181 

Belderbos J., 392, 475, 909 

Beldì D., 1117 

Belka C., 300, 1015, 1106 

Bell M., 1032, 1079 

Bellavita R., 426, 965 

Bellerive M., 655 

Bellyei S., 1216, 1329 

Beltramo G., 690, 692 

Ben-Dvaid M., 623 

Ben-Josef E., 966 

Benavente S., 646, 672, 795 

Bendini M., 1107 

Bendl R., 1115 

Beneventi S., 965 

Benezery K., 689, 1309 

Bengtsson E., 557, 559, 929, 994, 1343 

Benko A., 906 

Benson R., 945, 1167, 1183 

Bentzen J., 817 

Bentzen S., 19, 93, 115, 865 

Bentzen S. M., 116 

Berardi G., 980, 1022 

Beratis S., 956 

Berbeco R., 546 

Berenguer R., 1062 

Bereza I., 617, 731 

Berg C., 74 

Berg G., 935 

Bergantin A., 690, 692 

Bergdahl C., 1049 

Berger D., 121, 280, 460, 739 

Bergh P., 1089 

Berghmans T., 425 

Bergman A., 1001, 1278 

Bergmann R., 10, 314, 1479 

Bergmark K., 400 

Bergstrand E. S., 554 

Bergström P., 894, 1041 

Berkman S., 767 

Berkovsky P., 932 

Bermark B., 558 

Bernhardt P., 1468, 1502 

Bernstein Z., 356 

Berntsson A., 649 

Beroukas K., 963 

Berretta M., 683 

Berretta S., 683 

Berta L., 1244 

Bertelsen A., 137, 1355, 1374 

Berthelet E., 773 

Bertoni F., 1121 

Bertrand M. J., 1279 

Berveling M., 770, 967 

Berzins J., 595, 1408 

Betgen A., 1523 

Beuthien-Baumann B., 10, 314, 467, 1479 

Bewes J., 1467 

Beyer T., 5 

Bezjak A., 910 

Bhana S., 1498 

Bhandare N., 830 

Bhavsar D., 809 

Bhide S., 82, 846, 847 

Bhutani R., 724 

Bialas B., 567, 568, 573 

Bialas M., 427, 1091 

Bianchet K., 422 

Bianchi C., 454, 1004, 1042 

Bianchi L., 692 

Bianchi L. C., 690 

Biard D. S. F., 130 

Bibik R., 749 

Bidmead M., 82 

Biecek P., 631 

Bielack S., 1093 

Biete A., 580 

Biggs S., 603 

Bignardi M., 728 

Bijl H., 240, 849, 1347, 1348 

Bijl H. P., 1096 

Bilalis A., 928 

Bilge H., 1204 

Bilge S., 651 

Bill D., 452 

Bindoni L., 1107, 1188 

Birri S., 422 

Bischoff H., 884 

Bissonnette J. P., 910 

Bitaraf M., 1379 

Bittan H., 563 

Biver S., 1010 

Bizjak N., 1535 

Bjelkengren U., 1205, 1219, 1263 

Björk P., 1272, 1549 

Björk-Eriksson T., 361, 381, 1480 

Björksund C., 598 

Blackfield D., 62 

Blad B., 1259, 1515 

Blamek S., 658, 1344, 1346 

Blanchard P., 1540 

Blank L., 779, 1390 

Blank M., 985 

Block A., 1413 

Bloemen- van Gurp E., 488 

Blokzijl E., 1347, 1348 

Blom R., 1043 

Blomquist M., 1240 

Blower P., 1439 

Boarini B., 1362 

Bobek-Billewicz B., 1489 

Bocanek J., 142, 1213, 1402 

Boccon-Gibod L., 999 

Bock, de T., 849 

Bodez V., 1177, 1202 

Bodis S., 1020, 1555 

Bodzak D., 1258 

Boehmer D., 112 

Boeken Kruger A., 1023 

Boerma M., 177 

Boersma L., 384 

Bogner L., 1153, 1351 

Bogner P., 571, 906, 1123 

Bogusz M., 1553, 1554 

Boguszewicz L., 1344 

Boher P., 81 

Bohlin J., 282 

Bohoslavsky R., 91, 453 

Bohr Mordhorst L., 558 

Boiardi A., 1430 

Bokulic T., 1211 

Bol A., 49, 412, 461 

Bol G., 1171 

Boladeras A., 328 

Boladeras A. M., 701 

Bolla M., 12, 315 

Bolsi A., 292 

Bolstad Hysing L., 73 

Bolt R., 1096, 1347, 1348, 1419 

Bolton D., 1044 

Bolukbasi Y., 586, 615, 754, 1410 

Bolzicco G., 908, 998 

Bompas E., 794, 798 

Bonab A., 490 

Bonanni A., 590, 1111 

Bondar L., 547 

Bondar M., 1172 

Bondiau P. Y., 372, 1309 

Bonet Beltran M., 682 

Bonet M., 1389 

Bonfili P., 881, 979 

Bongartz R., 315 

Bonodeau F., 691 

Bonomo P., 645, 777, 833, 1358 

Bontovics J., 693 

Bonucci I., 912 

Book M., 291, 1488, 1503, 1507 

Boon G., 1152 

Bootsma G., 115, 116, 243, 893 

Borchers H., 246 

Borden van der A., 1347 

Borg T., 308 

Borges C., 349 

Borglund N., 1151 

Borgmann K., 434, 1432 

Boriano A., 1203 

Borojevic N., 716 

Borras J., 747 

Borresen-Dale A. L., 60 

Borst G., 909 

Bortfeld T., 490 

Bosmans G., 253, 334, 463, 665, 738 

Bosset J. F., 493 

Bossola M., 819 

Boterberg T., 1152 

Both S., 635, 778, 790 

Botterweck A., 893

AUTHOR INDEX 

Bottomley A., 874 

Bottomley D., 325, 1026, 1064 

Bottomley I., 1027 

Bouché O., 65 

Boukour Y., 1019 

Bourdin S., 1018 

Bourel V., 1497 

Bourgois N., 1251 

Bourhis J., 126, 130, 290, 360 

Bourne S., 1500 

Boutros M., 88 

Bouza A., 1406 

Bouzeya N., 1397 

Bouzin C., 489 

Bowden J., 1271, 1306, 1312 

Bowes P., 1289 

Bownes P., 325, 1306, 1312 

Boyko S., 1526 

Boz G., 715 

Braakman I., 472 

Braam P., 279 

Braat C., 902 

Brada M., 149, 228, 250, 552, 1184 

Brade A., 862, 910 

Bradley P., 321 

Brahme A., 8, 77, 1327, 1328, 1332, 1379, 

1400, 1442 

Brait L., 690, 692, 1430 

Brambilla A., 690, 692 

Brandberg Y., 450, 1049 

Brandenburg S., 258, 287, 1453 

Brandwijk R., 231 

Bratt O., 1043 

Bratteli K., 151 

Bravin A., 346 

Breen S., 86 

Breeuwsma A., 992 

Brehmer M., 559 

Breton I., 218 

Breton V., 1267 

Brett C., 1511 

Brettle D., 1157 

Breuers M., 483 

Brewster E., 187 

Brie I., 1494 

Brink C., 137, 302, 895, 1099, 1355, 1366, 

1374 

Bristow R., 67 

Brock J., 149, 228, 1184 

Brock K., 101, 394 

Brodin O., 1480 

Broggi S., 53, 296, 880, 980, 981, 1008, 1176, 

1460 

Brons S., 1384 

Brooks C., 1139 

Brouwer C., 1173 

Brown D., 1199 

Brown E., 1485 

Brown G., 272, 386 

Brown K., 132 

Brown M., 200 

Bruce G H., 583 

Brueggl M., 1361 

Bruheim K., 273 

Bruinvis I., 1545 

Bruland O., 1093 

Brun E., 361 

Brunckhorst E., 1242 

Brunet G., 1363 

Brunet-Benkhoucha M., 229 

Brunsting J., 1455 

Brusasco C., 1244 

Bruschini R., 793 

Bruzzi M., 338 

Bryant L., 564 

Bryant P., 1485 

Brzeska B., 939 

Bräutigam E., 316 

Brüchner K., 1479 

Buatti J., 982 

Bucciolini M., 338 

Buckey C., 1040 

Buckney S., 1417 

Budach W., 503 

Budiharto T., 356, 1067 

Budihna M., 852 

Buecher B., 1482 

Bueno G., 374 

Buffoli A., 276, 1119 

Buijs M., 1397 

Buijsen J., 245, 269, 285, 306, 697, 732, 738, 

865 

Bujko K., 696, 718, 722, 1544 

Bulski W., 839, 1226, 1258, 1260, 1261 

Bundschuh R., 95 

Bunton C., 1373 

Burgers S., 524 

Burke C., 1547 

Burke S., 1511 

Burlage F., 849 

Burnet N., 84, 305, 432, 433, 633, 1077, 1167, 

1183, 1315 

Burns M., 1441 

Burt P., 1138 

Burton K., 84, 633 

Buschbeck B., 1058 

Bussink J., 131, 310, 390, 469 

Butkiewicz D., 1433 

Butts C., 899 

Buwalda J., 779 

Bylund K., 982 

Byrne J., 83 

Byrnes R., 1068 

Bystrzycka J., 573 

Byther E., 422 

Byung Chul Y., 1449 

Bäck A., 1299, 1525 

Bäck S., 78, 142, 601, 1243, 1263, 1549 

Bäck S. , 1334 

Bäck T., 753, 1454 

Bäckmann E., 1151 

Béliveau-Nadeau D., 229, 1159 

Bø B., 308, 444 

Bühlmann R., 1102 

Bünte K., 1525 

Caballero B., 1129 

Caballero Delpozo S., 1551 

Cabeza M. A., 626 

Cabezas I., 747 

Caeiro M., 1370 

Cagni E., 29 

Cakýr A., 873, 1006 

Calabrese L., 793 

Calais G., 360 

Calamia E., 1203 

Calandrino R., 296, 980, 981, 1008, 1176, 

1460 

Calcagni M. L., 889 

Califano J., 832 

Calvo F., 244 

Calvo Fernandez A., 768 

Calvo O., 1297 

Calvo Ortega J. F., 1298 

Cambray M., 701 

Cambria R., 1028, 1039, 1054, 1414 

Camille V., 12 

Camlýca H., 1006 

Campion L., 798, 1018, 1482 

Campos de Araujo A. M., 1211 

Campostrini F., 276 

Canals E., 1352, 1353 

Canazza A., 1430 

Canby-Hagino E., 449, 1057 

Candamio Folgar S., 700 

Candela F., 1550 

Canitano S., 248 

Cannon M., 1045 

Canonico D., 1107, 1188 

Canters R., 758 

Cantor P., 999 

Canziani L., 585 

Canzonieri V., 715 

Cao Y., 637 

Capdevila A., 582 

Capdevila J., 708 

Capela M., 1281, 1313 

Capella G., 1426 

Capirci C., 269 

Capizzi R., 777 

Caporaso G. J., 62 

Capparella R., 1111 

Caprile P., 104 

Caradec P., 1231 

S 497 

Caravatta L., 236 

Carballo Castro A., 700 

Cardoso I., 349, 1532 

Cardoso M., 146 

Carey B., 325, 1104, 1306 

Carino R., 592, 611 

Carlsen E., 273 

Carlsen J. M., 468 

Carlson D., 141 

Carlsson T., 1473 

Carlsson Tedgren , 1255 

Carmona V., 1396 

Carrasco de Fez P., 1196 

Carrasco Rodríguez J. L., 1287 

Carrascosa C., 1128 

Carrie C., 958 

Carrier J. F., 229, 347, 1159, 1279 

Carriero A., 1117 

Carrle D., 1093 

Carroll D., 1521 

Carson K., 877 

Cartei F., 683, 1163, 1362 

Carter P., 87 

Carvalho A. L., 1249, 1300 

Carvalho L., 1201 

Carvoeiras P., 349, 1532 

Casado E., 708 

Casale M., 426, 656, 662, 669 

Casals Farran J., 1298 

Casamassima F., 912 

Casas F., 879 

Cascio E., 490 

Caskie V., 803 

Caspiani O., 590, 1111 

Cassoni A., 1093 

Castadot P., 97, 1019, 1251 

Castaldo G., 1323 

Castellanos E., 451, 991, 993, 994, 1050, 

1078 

Castelli J., 606 

Castelo J., 1245 

Castiglioni S., 728 

Castro D., 566 

Castro Gomez E., 700 

Castro J., 1425 

Castro J. E., 612 

Cats A., 271 

Cattaneo G. M., 1008, 1176, 1460 

Cattaneo M., 296, 880 

Cattani F., 793, 1028, 1039, 1051, 1054, 1414 

Cattari G., 1016, 1166 

Cattell H., 78, 141 

Catton C., 1412 

Caudrelier J. M., 610 

Cavaco A., 1201 

Cavedon C., 908, 998, 1253, 1291 

Ceberg C., 299, 1549 

Ceberg S., 78, 142, 601, 1243, 1334 

Ceder R., 1484 

Cederlund C. G., 1089 

Ceha H., 1212 

Celler A., 861 

Cellini F., 268, 592, 611, 712, 890, 969 

Cellini N., 236, 645, 674, 706, 1070, 1081, 

1492 

Cengiz M., 577, 1458 

Cerezo L., 460, 676 

Cerreta V., 640 

Cervo E., 660, 961, 1082 

Cesario A., 889, 890 

Cetintas S., 641 

Chahine G., 725 

Chai X., 1181 

Chakarova A., 748 

Chakarova R., 598, 1299 

Chalmers K., 553 

Chamorey E., 606 

Chan N., 67 

Chan O., 776, 780 

Chan S. H., 837 

Chang A. R., 1499 

Chang H. M., 707 

Chang Y. C., 88 

Chantler H., 82, 870 

Chao C., 27 

Chapman C., 564 

Charbonnel C., 1018


Chargari C., 284, 757, 1251 

Charrier J., 1482 

Chatterjee K., 570 

Chaudhri M. A., 1383 

Cheah N., 822 

Checcaglini F., 965 

Chee R., 1079 

Chee-Wai C. P., 1072 

Chelminski K., 1226, 1258 

Chen Q., 92 

Chen X., 681 

Chen Y., 99 

Chen Y. J., 62, 333 

Chen Z., 946 

Cheng C. W., 542, 978, 1055, 1318 

Cheng J., 687 

Cherel M., 1482 

Cherian S., 826, 945 

Cherpak A., 105 

Chetty I., 92 

Chew A., 773 

Chiappella A., 918 

Chichel A., 596, 824, 1017, 1063 

Chie E. K., 587, 679, 688, 698, 1234 

Chiesa F., 793 

Chiesa S., 674, 712, 969, 1492 

Chimienti E., 422 

Chin J., 449, 1057 

Chin L., 90 

Chinita P., 1155 

Chiovati P., 840, 882, 1121 

Chirag M., 820 

Chiramana H., 820, 941 

Chirico L., 662, 669 

Chitallia A., 1138 

Chmiel A., 638 

Chmielnik E., 1087 

Cho B., 477 

Cho B. K., 653 

Cho C., 729, 730, 751, 986 

Cho H., 904 

Cho J., 910 

Cho J. H., 643, 714, 805 

Cho M. J., 1290 

Cho S. J., 1221 

Cho Y., 101 

Choi C., 729, 730, 751, 986 

Choi C. W., 837 

Choi D. H., 583 

Choi E. K., 707 

Choi H. J., 1461 

Choi J. H., 653, 1450 

Choi M., 1170 

Choi Y. M., 1461 

Chorazy M., 1433 

Choudhury A., 800, 856 

Chouin N., 1270 

Chow E., 966 

Chow S. K., 837 

Christensen G., 415, 1525 

Christian N., 461, 1019 

Christianen M., 849 

Christine K., 968 

Chu Q., 899 

Chua B., 624 

Chul Shin K., 1290 

Chun M., 1466 

Chung D. J., 734 

Chung J. B., 1234 

Chung P., 1412 

Chung W., 1124, 1228 

Chung W. K., 734, 907 

Ciammella P., 1016, 1166 

Cianchetti M., 788 

Ciechowicz J., 983, 1528, 1538 

Cilla S., 102, 236, 1185 

Ciocca M., 793, 1039, 1414 

Cionini L., 639 

Ciresa M., 592, 611, 890 

Cirio R., 1244 

Cirrone P., 338 

Ciurlia E., 706 

Ciurlionis L., 109, 1330 

Ciusani E., 1430 

Claes E., 1478 

Claesson K., 1464 

Clark C., 82 

Clarke J., 877 

Claus Erik Andersen C. E., 1380 

Clayton-Lea A., 87, 657, 960, 1109, 1511 

Cleary L. A., 539 

Clemenceau S., 1440 

Clemente S., 942, 1323, 1508 

Clermont C., 686 

Clivio A., 79, 106, 140, 335, 1199 

Coccaro M., 942 

Coche-Dequant B., 845 

Coco C., 715 

Cocquyt V., 237 

Coebergh J., 39 

Coelho M., 349 

Coffey M., 1521 

Coghe M., 775, 1152 

Cohen S., 687 

Cohn-Cedermark G., 451, 991, 993, 994, 1078 

Cola S., 59 

Colak F., 577 

Coleman L., 1513 

Coles C., 317, 432, 433, 530, 1330 

Coliarakis N., 963 

Coll J., 582 

Colla E., 1341 

Collan J., 1443 

Collette L., 315, 356 

Collins C., 1109 

Collomb Patton V., 81 

Coloby P., 1085 

Colombo F., 908 

Commowick O., 372 

Congedo M. T., 889 

Conijn S., 1397 

Conte M., 808 

Convery H., 1118 

Conway J., 83 

Cook G., 792 

Cooks T., 563, 574, 1501 

Coolens C., 1462 

Coomber H., 553, 752 

Cooper R., 675, 1104 

Copeland K., 127 

Coppes R., 258, 261, 287, 1453, 1455 

Cora S., 908, 1253, 1291 

Coradi T., 1102 

Coray A., 292 

Corbo F. M., 889 

Cordes N., 68, 69 

Cormack R., 90 

Corner C., 564 

Cornes P., 553, 576 

Corr F., 1547 

Correa C., 234 

Cortés-González J., 1050 

Corvo R., 18 

Cosar Alas R., 588 

Cosgrove V., 877 

Cosset J. M., 535 

Cossmann P., 148, 215, 318, 1144, 1420 

Costa Ferreira B., 226, 605, 888, 1114, 1269, 

1281, 1313, 1375, 1403 

Costa J., 372 

Costa L., 290 

Costa P., 1085 

Costantini S., 656, 662, 669, 970, 971 

Coucke P., 1010 

Courdi A., 606 

Cousins C., 535 

Coutinho A., 349, 1532 

Couture C., 898 

Couñago F., 676 

Cowan R., 984, 1027 

Cox J., 441, 541 

Coyle C., 800, 856 

Coza O., 1494 

Cozzarini C., 980, 981, 1008, 1022 

Cozzi L., 79, 106, 140, 142, 335, 742, 1199 

Craig A., 1521 

Craven-Bartle J., 1389 

Crawford E., 449, 1057 

Crellin A., 675, 723 

Cremers F., 1223, 1230, 1237, 1242 

Crespi S., 639 

Creutzberg C., 63, 167 

Crevecoeur H., 796 

Crijns W., 1349, 1398 

Croci D., 1430 

Crol P., 1342 

Cromvik C., 538 

Crop F., 222 

Crosbie J., 1210 

Crosby D., 187 

Crowley C., 1373 

Crownover R., 1336 

Crucitti A., 706 

Crundwell M., 64, 936 

Cruz A., 676 

Cserháti A., 693, 1101 

Cucchiaro S., 1350 

Cuijpers J., 139, 213, 1141, 1280 

Culig Z., 35 

Cummings B., 86, 785 

Cunningham M., 1025, 1030 

Cvitkovic F., 65 

Cygler J., 105, 1211 

Czaja K., 638 

Czarnota G., 1487 

Czebek-Szebek P., 1356 

Czech T., 664 

Czigner K., 1033 

Czuchraniuk P., 1372 

Czyzew B., 1066 

Czyzewski K., 1433 

Cámara-Turbí A., 1364 

D’Agostino G. R., 244, 268, 632, 645, 706, 

930, 1358, 1492 

D’amico A., 673 

D’Amico R., 352 

D’Angelillo R. M., 592, 611, 890 

D’Angelo E., 268, 712 

D’Este C., 452 

D’Imporzano E., 912 

D’Onofrio G., 102, 1185 

D’Souza D., 579 

Dabkowski M., 562 

Dag N., 782 

Dagnault A., 630, 898 

Dagoglu N., 1204 

Dahele M., 910 

Dahm-Daphi J., 1432 

Dahmane R., 1084 

Daisne J. F., 166, 686, 796, 1350 

Daley F., 71 

Dalhaug A., 642 

Dall’Oglio S., 673 

Daly K., 1079 

Damen E., 223, 392, 475, 909 

Damilakis J., 917, 1294 

Dandekar P., 792 

Dannenberg M., 575 

Dardoufas K., 1114 

Darendeliler E., 1006, 1204 

Das I., 1318 

Dasu A., 436, 1316, 1327, 1332 

Dasu I. L., 1332 

Davidson M., 146 

Davidson S., 1441 

Davis B., 356 

Dawson L., 86, 785 

Dawtal V., 547 

De Angelis V., 970, 971 

De Bari B., 777, 833, 930, 1492 

De Bast M., 461 

de Boer C., 476 

de Boer H., 96, 483, 1156 

de Boer J., 233 

de Bois J., 330, 478 

De Brabandere M., 1193 

de Bree R., 277, 289 

De Cicco L., 793, 1039, 1051 

de Cobelli O., 1028, 1039, 1051, 1054 

De Fazio S., 590 

De Gersem W., 529, 775 

De Guglielmo E., 1163, 1362 

de Haan G., 1455 

de Haan P., 1113, 1212 

De Haas-Kock D., 285, 732 

De Hertogh O., 1019 

De Jaegher I., 32 

de Jong D., 1088 

de Jong I. J., 992 

de Jong J., 428

AUTHOR INDEX 

de Jong M., 428, 1122 

de Jong R., 233, 304, 684 

De Keyzer F., 309, 462 

de Kort G., 756 

de Kruijf W., 119, 1367, 1368 

de la Fouchardière A., 958 

De la Fuente Muñoz I., 1013 

de la Torre A., 879 

de la Torre M., 1497 

De Laroche G., 270 

De Marchi F., 715 

De Martin E., 1004 

De Meerleer G., 111, 237, 297, 543, 988, 

1007, 1035, 1036, 1152 

De Neve W., 25, 237, 297, 529, 543, 775, 876, 

1007, 1035, 1036, 1152 

De Ost B., 1191 

de Pan C., 816, 1011, 1524 

De Paoli A., 715 

de Patoul N., 1296 

de Pree I., 547, 1172 

de Reijke T., 1052 

De Ridder M., 525, 711 

De Rose F., 833 

De Ruysscher D., 114–116, 118, 243, 285, 

297, 313, 334, 337, 447, 456, 

463, 732, 738, 865, 876, 893, 

900, 914, 944, 987, 1517 

De Santis M., 777, 833 

De Stefano V., 969 

De Vos K., 1002 

de Vreeze R., 1088 

De Wagter C., 237, 529, 543, 1007, 1036 

De Wever W., 1326 

de Wilt H., 271 

de Winton E., 624 

Deamen M., 289 

Dean C., 1104 

Dean J., 305, 1167 

Dearnaley D., 98, 433 

Deasy J., 419, 464 

Debeb B., 23 

Debougnoux-Huppertz R., 253, 665 

Debus J., 179, 262, 745, 884, 938, 1092, 1481 

Deckers F., 727 

Dees-Ribbers H., 1116 

Defresne F., 489 

Degli Esposti C., 840, 882 

Deheneffe S., 796 

Dehing C., 115, 245, 269, 876 

Dehing-Oberije C., 1517 

Dejean C., 1391 

Dekker A., 118, 297, 313, 334, 337, 463, 479, 

482, 488, 697, 738, 900, 914, 

944, 987, 1137, 1207 

Delaere P., 462 

Delana A., 1225, 1369 

Delanian S., 943 

Delgado J. M., 358 

Delgado Perez J. M., 771, 869, 959 

Delichas M., 888 

Delidou E., 841 

Delingette H., 372 

Dell’Oca I., 296, 880, 1176 

Delor A., 1296 

Delouya G., 1047 

Delpon G., 798, 1363 

Delrue L., 237 

Delso G., 95 

Demanes J., 1080 

Demaria S., 510 

Demenagas D., 928 

Demir O., 765 

Demirci S., 586, 615 

Demirel C., 1429, 1477 

Demiroz C., 823, 848 

Demizu Y., 827, 886 

den Hollander S., 76, 1519 

Dengra J., 947, 1105 

Dengra P., 964 

Denham J., 452 

Denis de Senneville B., 1180 

Denis J. M., 1296 

Denys H., 237 

Deodato F., 236 

Deprez P., 360 

Depuydt T., 1213, 1233, 1327, 1398, 1402 

Derbyshire S., 1310 

Derczy K., 1216 

Derda K., 434 

Derie C., 775 

Deshpande D., 561, 742, 1422 

deSouza N., 1118 

Despres P., 1047 

Dessard N., 924 

Destouni E., 1359 

Detti B., 1090, 1184 

Deutsch E., 126, 130 

Deutschmann H., 892 

Deville C., 635 

Dewas S., 1540 

Dharancy S., 691 

Dhawtal G., 1172 

Di Carlo V., 244 

Di Genesio Pagliuca M., 979 

Di Gesù C., 1081 

Di Lenardo F., 585 

Di Lullo L., 236 

Di Muzio N., 296, 880, 980, 981, 1008, 1022 

Di Peri D., 1363 

Di Rienzo L., 674 

Di Rito A., 1070, 1081 

Di Staso M., 881, 979 

Diaz A., 1403 

Dicker A., 404 

Dieckmann K., 55, 664 

Dienemann H., 524 

Dierckx R., 992 

Diez P., 1235 

Digesù C., 102, 236 

Dijkema T., 279, 843, 854 

Dikomey E., 434, 1432 

Dimitrios K., 968 

Dimofte A., 790, 1268 

Dimopoulos J., 121, 123, 197, 280, 283, 739 

Din O., 916 

Dinapoli N., 249, 268, 352, 632, 712, 777, 833, 

930, 1358, 1506 

Dincer M., 767 

Dingemans A. M., 115, 243 

Dinh Dang N., 593 

Dinkel J., 745 

Dinshaw K., 561, 724, 742, 744, 1422 

Dirix L., 727 

Dirix P., 239, 309, 462, 814, 1326, 1327 

Dirkx M., 227, 483, 1143, 1556 

Dirx M., 893 

Disci R., 767, 786 

Divgi C., 753 

Dizdar Y., 1006 

Djordjevic M., 1160, 1162 

do Carmo Lopes M., 1313 

Do Hoon L., 1449 

Doble A., 1167, 1183 

Dobler B., 90, 1153, 1351 

Doerfler A., 431 

Dogan A., 577, 937 

Dogan N., 1354 

Dogan S., 641 

Dohm O., 484 

Doleckova M., 932 

Dolezelova H., 764 

Dollinger G., 1431 

Dolsma W., 144, 147, 1371 

Dom B., 802 

Dominczyk I., 1437 

Domine M., 879 

Domingo C., 1245 

Dominguez S., 691 

Domínguez M. A., 811 

Donach M., 510 

Donath D., 229 

Dondi D., 276 

Donetti M., 1244 

Doneux A., 972 

Dong Wha L., 583 

Dongryul O., 1449 

Donnarieix D., 1267 

Dononi E., 840, 882 

Donovan E., 317, 1330 

Doodeman B., 684 

Doornaert P., 277, 278 

Doran S., 1192 

Drouet F., 794, 798 

Drove N., 626 

Drud E., 1230 

Drugge N., 523, 1525 

Duane S., 83 

Dubois J. B., 315 

Dubois L., 256, 390, 470 

Duburque C., 691 

Dubus F., 845 

Duch M. A., 1190, 1338 

Duchateau M., 135, 525 

Duclos F., 445 

Ducreux M., 65 

Duffy M., 1138 

Dumas I., 193, 284, 757 

Dumenigo C., 358 

Dunberger G., 282, 307, 762, 1444 

Dundar E., 578 

Dunne M., 1045 

Dunning A., 432, 433 

Dunscombe P., 214, 995 

Dunst J., 150 

Duppen J., 304, 354, 522, 602 

Duret A., 958 

Dusko L., 628 

Dutoit S. H., 458 

Dutta P., 778 

Duzenli C., 861 

Dvorak J., 685 

Dwivedi R., 847 

Dyker K., 800, 856 

Dymnicka M., 596, 1063 

Dyson C., 803 

Dyzmann-Sroka A., 769 

Dziadziuszko R., 549 

Dávila Fajardo R., 1013 

Dávila-Fajardo R., 1131, 1364 

Dérczy K., 1329 

Dörr E., 153 

Dörr W., 153, 286, 288 

Eagle S., 516 

Eakin R., 877 

Eapen L., 1069 

Early S., 442 

Eaton D., 1315 

Eberhard V., 142 

Eberhardt B., 617 

Eberlein K., 1471 

Ebert M., 420, 452, 1467, 1474 

Ebi J., 844 

Eble M., 246, 297 

Ectors N., 9 

Edincik C., 641 

Edmund J., 1380 

Edouard M., 346 

Edwards C., 82 

Eekers D., 1407 

Eenink M., 684 

Efi P., 973 

Efrati M., 563 

Efremidis A., 425 

Efstathia G., 968 

Eggleton R., 1373 

Egli P., 1274 

Egmond van J., 407 

Eichbaum M., 745 

Eicheler W., 431 

Eiland T., 306 

Eilertsen K., 1151, 1175 

Einarsdottir M., 1043 

Eiras M., 217, 443 

Eisbruch A., 171, 279, 474 

Eivazi M. T., 1265 

Ekberg L., 361, 523, 1334 

Eke I., 69 

Eklund K., 103 

El Barouky J., 1238 

El-Sebaie M., 1435 

Elgqvist J., 753 

Eliasziw M., 429 

Elkhuizen P., 145, 602 

Ellaume H., 346 

Ellerbrock M., 1384 

Elliott R., 432, 433 

Elliott T., 984, 1000 

Elmberger G., 810 

Elmer S., 1222 

S 499


Elmroth K., 1464 

Elstrøm U. V., 513, 1148, 1404 

Emans D., 1207 

Emmerson L., 460 

Emri S., 901 

Emzins D., 595, 1408 

Encheva E., 1459 

Endres E., 788 

Eng T., 1232 

Engberg J., 1530 

Engels B., 711 

Engelsman M., 297, 498, 900, 1377 

Enghardt W., 206, 1178 

Engineer R., 724, 742, 744 

Engstrom K., 1089 

Engström P., 170, 299 

Engstrøm M., 1175 

Enmark M., 838 

Eom K. Y., 698 

Eralp Y., 767 

Erasmus C., 254 

Erdal N., 1429, 1477 

Erdemli E., 1456 

Ergen A., 1006 

Ericsson A., 784 

Ericsson M., 1014 

Eriksen J. G., 458, 459 

Eriksson D., 343 

Eriksson J., 1240 

Eriksson K., 1014 

Erkmen K., 655 

Erler J., 389 

Errico A., 1070 

Erridge S., 864 

Ersmark T., 224 

Erven K., 219 

Escobar J., 869 

Escoval A., 217, 443 

Escribano A., 1129 

Esfahani M., 1409 

Esik O., 1216 

Eskandarian M., 1046 

Esquivel C., 220, 1232, 1336, 1403 

Essers M., 1407 

Essler M., 95 

Estall V., 84 

Estall V. J., 1315 

Esteve F., 346 

Eswar C., 89, 996 

Etienne P. L., 270 

Eto H., 925 

Etou H., 619 

Ettore F., 606 

Etzyoni R., 574 

Eudaldo T., 1196, 1389 

Eun Kyung C., 885 

Eun Seog K., 583 

Evans M., 348 

Evans P., 1118 

Evelo C., 437 

Everaert H., 711 

Evers C., 1178 

Evrensel T., 661, 927 

Fabbri S., 1163, 1362 

Faber H., 258, 287, 1453 

Fabrini M. G., 639 

Fairchild A., 966 

Fairfoul J., 305, 317, 1167, 1183 

Faivre-Finn C., 864, 1138 

Falck Schmidt S., 957 

Falco T., 99 

Fareed M., 774, 821 

Farhan F., 457 

Farhat F., 725 

Faria J., 1552 

Faria S., 1126 

Fariselli L., 690, 692, 1430 

Farkas R., 1216, 1329 

Farnebo L., 260, 1493 

Farnell D., 1441 

Farr J., 339 

Fasoulaki A., 917, 952 

Fastner G., 244 

Fatehi D., 758 

Favaudon V., 1423 

Favretto M. S., 908, 998 

Fazekas O., 1101 

Fazio F., 296, 880, 980, 981, 1008, 1022 

Featherstone C., 915 

Feenstra J., 816 

Feichtinger J., 316 

Feigen M., 589 

Fekkes S., 944, 1137 

Fellin G., 454, 1004, 1042 

Fenton D., 899 

Fenton-Kerimian M., 510 

Fenwick J., 89, 107 

Fernandes V., 217 

Fernandez E., 1275 

Fernando W., 1032 

Fernberg J. O., 361 

Fernández J., 1013 

Fernández-Varea J. M., 182, 1215, 1270 

Fernández-Velilla E., 613, 868, 1551 

Feron O., 388, 489 

Ferrand R., 1440 

Ferrandina G., 236 

Ferrarese F., 1107 

Ferrari V., 234 

Ferreira A., 217 

Ferreira I., 924 

Ferreira P., 349 

Ferreiros Vázquez N., 1298 

Ferrer F., 328 

Ferrer M., 328 

Ferrero J. M., 606 

Ferro R., 358 

Ferruccio F., 1176 

Fersino S., 1070, 1081 

Feuvret L., 1440 

Feyer P., 434 

Fiandra C., 1016, 1166, 1452 

Ficek K., 252, 658, 695, 1346 

Fidanzio A., 102, 1185 

Fidarova E., 280, 739 

Figueira A. R., 1249, 1300 

Figueiredo M., 1155 

Fijalkowski M., 573 

Fijuth J., 677, 749, 913 

Filippi A. R., 918, 1452 

Fine R., 320 

Fiore M., 592, 611, 890 

Fiorentino A., 632, 645, 833 

Fiorica F., 683, 1163, 1362 

Fiorino C., 296, 454, 880, 980, 981, 1004, 

1008, 1022, 1042, 1176, 1460 

Fischer M., 1237 

Fisher E., 1494 

Fisher M., 374 

Fisher W., 1021 

Fiszer-Kierzkowska A., 1489 

Fitton I., 522 

Fitzpatrick D., 1045 

Fjellsboe L., 73 

Flammia C., 1163, 1362 

Flatin Lien L., 308 

Flentje M., 491, 545 

Fletcher C., 108, 1206 

Floore A., 524 

Florin M. C., 425 

Flynn R., 62 

Foa P., 460 

Fodor A., 880, 1051 

Fodor C., 1028, 1039, 1051, 1054 

Fodor E., 1101 

Fodor J., 569, 680, 834, 1033, 1076, 1395 

Foertsch D., 1021 

Fogaroli R., 808 

Fogliata A., 79, 106, 140, 742, 1199 

Fogliata Cozzi A., 335 

Foley G., 1498 

Fongione S., 1119 

Fontan L., 1107, 1188 

Fontbonne J. M., 81 

Fonteyne V., 111, 237, 297, 543, 988, 1007, 

1035, 1036 

Foppiano F., 950, 1042 

Foran B., 1165 

Forastiere A., 832 

Ford A., 803 

Forgacs G., 1033 

Forman J., 449, 1057 

Formenti S., 510 

Foro Arnalot P., 1105, 1551 

Foro P., 613, 868, 947, 964, 1275, 1509 

Foroudi F., 541 

Forssell-Aronsson E., 935, 1468, 1473, 1502 

Fortin M. A., 1047 

Fortunato M., 659 

Fossati P., 1028 

Foti C., 1119 

Foulquier J. N., 1257 

Fournier B., 871 

Fournier C., 1481 

Fournier-Bidoz N., 1238 

Fourquet A., 315, 370 

Fraass B., 100, 474 

Fragomeni R., 1111 

Franceries X., 1321 

Francescon P., 908, 998, 1253, 1291 

Franchi B., 1054 

Franchisseur E., 373 

Francisco R. M., 580 

Franck-Lissbrant I., 1049 

Franckena M., 758 

Franco P., 1016, 1166 

Francois E., 65, 689 

Francois P., 30 

Franken E., 1556 

Franklin A., 780, 812, 813 

Franklin I., 452 

Franks K., 910 

Fransson P., 154, 1014, 1041 

Franzese P., 881, 979 

Franzén L., 1041 

François E., 270 

Fras A. P., 572 

Frascino V., 632, 674, 969, 1070, 1081, 1358, 

1492, 1506 

Frascogna V., 126 

Fraser D., 99 

Frazier J., 1021 

Fredh A., 1189 

Fredheim C., 444 

Freedman G., 687 

Freedman K., 510 

Freeman C., 348 

Freeman K., 1360, 1373 

Freitas N., 670 

Freling N., 779 

French C., 576 

Frese M. C., 336 

Frey B., 300, 1015 

Frezza G., 840, 882, 1121 

Fried D., 329 

Friedl A., 1431 

Friedman J., 655 

Friesland S., 361, 523, 557, 835, 1425, 1446 

Friso M. L., 715 

Frohlich G., 1076 

Frost S., 753 

Frydenberg M., 1044 

Fröhlich G., 569, 948, 1395 

Fuentes M. J., 1389 

Fujak E., 1274 

Fujimoto K., 720, 911, 1031 

Fukuda K., 721 

Fukumitsu N., 710, 721 

Fukumoto M., 591, 1125 

Fuller C. D., 1170 

Fumagalli L., 1430 

Fundowicz M., 824, 1094 

Fung G., 437, 876, 1517 

Furre T., 1151 

Furstoss C., 1279 

Fusco V., 426, 942 

Fuss M., 1258 

Fyles A., 101, 238, 1520 

Fýrat P., 1456 

Gabbani M., 673 

Gabrys D., 617, 789 

Gach T., 718 

Gackle M., 214 

Gadient T., 1021 

Gagel B., 246 

Gagliardi F., 1210 

Gagliardi G., 523, 1179 

Galalae R., 1058 

Galerani A. P., 1406

AUTHOR INDEX 

Gallego S., 255 

Gallucci G., 942 

Galwas-Kliber K., 617 

Gambacorta A., 715 

Gambacorta M. A., 245, 249, 352, 712, 969, 

1358 

Gangopadhyay A., 609 

Gangsaas A., 1156 

Ganswindt U., 300, 1015, 1106 

Gao J., 542 

Gao J. Z., 1055 

Gao Z., 978 

Garcia D., 320 

Garcia F., 1196 

Garcia Fernandez R., 1013 

Garcia Grande A., 1129 

Garcia J., 1097 

Garcia R., 202, 1177, 1202 

Garcia-Fuste M. J., 1245 

Garcia-Huttenlocher H., 1092 

Garcia-Sabrido J. L., 244 

Garcic J., 764 

García-Ruíz J., 1097, 1504 

Gardani G., 276 

Gardner S., 152 

Garelli S., 950 

Garg M., 783, 850 

Garganese G., 236 

Garibaldi C., 1028, 1039, 1054 

Garmo H., 1507 

Garrett W., 87 

Garrido Beltrán L., 1298 

Gaspar Martinez C., 891 

Gassa F., 1288 

Gatto G., 793, 1039, 1051 

Gaudaire S., 794 

Gaudino D., 592, 611 

Gauthier I., 1159 

Gauthier-Bizier S., 1047 

Gava A., 276 

Gava M., 269 

Gawkowska-Suwinska M., 1489 

Gawrychowski J., 1433 

Gay H., 905 

Geets X., 49, 97, 412 

Geiger F., 1058 

Geinitz H., 883 

Genest P., 610 

Genhart S., 148 

Gennatas K., 781 

Georg D., 55, 163, 183, 283, 1258 

Georg P., 739 

George B., 1440 

Georgieva S., 748 

Geraedts W., 116, 243, 893 

Gerard J. P., 65, 689, 1394 

Gerard K., 1321 

Gerard-martin S., 1373 

Gerlach B., 621 

Geropantas K., 791 

Gershkevitsh E., 345 

Gete E., 1357 

Gevaert T., 135, 525 

Gez E., 1410 

Ghaderi M., 1425 

Ghalibafian M., 924 

Ghaly M., 575, 1068 

Ghielmetti F., 1430 

Ghilezan M., 324 

Ghobadi G., 1453 

Ghorai S., 609 

Ghosh Dastidar A., 570 

Ghosh K., 570 

Ghosh S., 966 

GhoshDastidar A., 609 

Ghosn M., 725 

Giaccone G., 524 

Giannopoulou E., 1470 

Gianolini S., 1004 

Giantsoudi D., 1168, 1195, 1375 

Gidding C., 254 

Gigante M., 422 

Giglioli F., 1452 

Giglok M., 567, 568 

Gil A., 1128 

Giles A., 1487 

Gilhuijs K., 512, 622 

Gill B., 861, 1278 

Gillham C., 829, 1434 

Gillion N., 284, 757 

Gilson P., 1021 

Gimeno J., 120 

Ginestet C., 1209, 1288 

Ginjaume M., 1190, 1338 

Ginot A., 689 

Giocanti N., 1423 

Giordano C., 600 

Giorello C., 575, 1068 

Giorgi C., 656, 662, 669 

Giovanni C., 1508 

Giovannini M., 65 

Giovinazzo G., 853 

Giphart-Gassler M., 486, 487 

Girabent-Farrés M., 1504 

Giralt J., 7, 255, 460, 582, 646, 672, 708, 795 

Girinsky T., 924 

Girones R., 891 

Gisterek I., 625, 631 

Gitsels E., 1548 

Gittleman M., 320 

Giuliacci A., 1244 

Givhechi N., 1244 

Gkogkou P., 781 

Gladkova N., 755 

Gladstone D., 655 

Glaholm J., 822 

Glavak C., 906 

Gleeson M., 87, 776, 812 

Gleeson P., 452 

Glimelius B., 409, 551 

Glimelius L., 224 

Gluszko J., 348 

Glynne-Jones R., 564, 705 

Gneveckow U., 1144, 1420 

Goharian M., 214 

Goitein G., 292, 949, 1376 

Goksel E., 1204 

Goldman B., 1057 

Golen M., 274 

Goleñ M., 1087 

Gombosova J., 764 

Gomellini S., 248, 988, 1029, 1056 

Gomez Caamaño A., 700 

Gomez-Hassan D., 637 

Gomola I., 142, 1213, 1233, 1402 

Gonzales S., 1032, 1048 

Gonzalez Patiño E., 612 

Gonzalez V., 1198, 1341, 1396 

González A., 1013 

González Rodríguez F., 700 

González-López A., 1131, 1364 

Gonçalves M., 358 

Goor C., 581, 1002 

Goossens J., 1002, 1191 

Gopalan S., 875 

Gorzov P., 1187 

Goswami J., 570 

Goulart F., 647 

Gould K., 325 

Gouliamos A., 726 

Gouraud W., 1482 

Gourgou-Bourgade S., 270 

Gourin C., 832 

Goñi M., 811 

Graabæk Andersen C., 627 

Grade M., 1478 

Grafstrom R. C., 1484 

Graham L., 575, 1068 

Grahn C., 1518 

Gramaglia A., 640 

Granero D., 120, 125, 565, 1198, 1250, 1282, 

1283, 1341, 1393, 1396 

Granlund U., 558, 1239 

Granone P., 889, 890 

Grau C., 117, 332, 1148, 1182 

Gravina G. L., 881, 979 

Greco C., 592, 611, 890 

Greco F., 1185 

Green D., 540 

Greene T., 516 

Greilich S., 1382 

Grenacher L., 185 

Greubel C., 1431 

Gribaudo S., 667, 763, 953, 1386 

S 501 

Grigsby P., 281 

Grimaldi L., 102, 1185 

Grochowska P., 1226 

Groenendaal G., 311, 740, 1103 

Grohmann C., 1223 

Grootenboers D., 919 

Grosu A. L., 402 

Grout I., 1445 

Grusell E., 1382 

Gruszczynska E., 1066 

Grutters J., 243, 337, 987 

Grzadziel A., 1365 

Grégoire V., 10, 49, 56, 97, 159, 360, 372, 412, 

447, 461, 489 

Grénman R., 428 

Gröger A., 985 

Guarneri A., 1016, 1166, 1452 

Guazzoni G., 1022 

Guckenberger M., 491, 545 

Gudowska I., 341 

Guedea F., 328, 701 

Guerrero Urbano T., 82, 1360, 1373 

Guerriero C., 777 

Guglani S., 624 

Guglielmi R., 908, 998 

Guidi C., 590, 1111 

Guidi G., 1121 

Guido A., 793, 1039, 1051, 1414 

Guillén A., 358 

Guimond A., 372 

Guix B., 555 

Gulliford S., 847 

Gulyban A., 1216 

Gulybán , 1329 

Gumà J., 747 

Gunn G., 788 

Gunn O’Connor S., 1109 

Gunn-O’Connor S., 878 

Gunnar Adell G., 1495 

Guo B., 342 

Guoliang J., 1447 

Gupta A., 1264 

Gupta S., 744 

Guren M. G., 273 

Gurgul S., 1429, 1477 

Gurlek U., 848 

Gurley S., 603, 604, 650, 1037, 1038 

Gurtner K., 128 

Gustafson G., 324 

Gustafson P., 1089 

Gustafsson A., 1272 

Gustafsson A. L., 1516 

Gustafsson H., 1255 

Gustafsson M., 235, 1299 

Gustavsson H., 78, 142, 1334, 1549 

Gustavsson M., 1542 

Gutierrez A., 593, 888, 977, 1009, 1074, 1133, 

1195, 1297, 1469 

Gwiazdowska B., 1261 

Gwynne S., 955 

Gérard J. P., 270 

Göransson H., 1530 

Ha C., 342, 888, 1168, 1174 

Ha S., 587 

Ha S. W., 679, 698 

Haagen J., 286 

Haanstra B., 488 

Haas B., 1102 

Haas O., 374, 1145 

Haas R., 354, 1088, 1523 

Haasbeek C., 1141 

Haberkorn U., 884 

Hable V., 1431 

Habrand J. L., 297, 1440 

Haciislamoglu E., 577 

Hacker F., 546 

Hacking D., 1547 

Haddad A., 610 

Hadjiev J., 571, 906, 1123 

Hadjieva T., 1459 

Haertl P., 1351 

Haffty B., 320 

Haga A., 990, 1322 

Hage J., 289 

Haglund E., 753 

Hahn S., 865


Haider I., 774 

Haie-Meder C., 193, 284, 757 

Haigentz M., 783, 850 

Hainfellner J., 664 

Haji N., 88 

Halkett G., 441 

Hall E., 64, 936 

Haller K., 949 

Hallissey L., 33 

Hallqvist A., 801 

Halon A., 625 

Hamada N., 591, 1125 

Hamamoto Y., 867 

Hameed S., 774, 821 

Hammarsten O., 1486 

Hammer J., 316 

Hamming-Vrieze O., 241 

Han C., 333 

Han W., 587 

Handley M., 1048, 1533 

Hanna G., 877 

Hannoun-Levi J. M., 689 

Hansen C., 1099 

Hansen C. R., 1374 

Hansen K. H., 895 

Hansen O., 302, 895, 1366, 1374 

Hansen V., 98, 1139, 1184, 1421 

Hansen V. N., 82, 516 

Hao D., 429 

Hara M., 921 

Haraldsson A., 894 

Harari P., 93 

Harasim J., 1433 

Harden S., 870 

Harel F., 630, 898 

Haresh K., 766 

Harima Y., 1490 

Haring B., 213, 1141 

Harmenberg U., 929, 993 

Harms W., 745 

Harper D., 1513 

Harrington K., 127, 792, 846, 847 

Harrington P., 432 

Harris A., 1498 

Harris E., 234, 317 

Harris J., 62 

Harris M., 1138 

Harrison M., 705 

Hartel C., 1481 

Hartford A., 655 

Harting C., 259 

Hartley A., 822 

Hartmann G. H., 104 

Hartsell W., 966 

Hasan Y., 1080 

Haselmann R., 884 

Hashemi B., 1200, 1262, 1265 

Hassler M., 664 

Hata M., 920 

Hatano K., 750 

Hatano M., 663 

Hatfield P., 675, 723, 1104 

Hatton M., 916, 1165 

Hattoori C., 925 

Hattori C., 619 

Hauer-Jensen M., 177 

Haugen H., 801 

Hauptmann M., 275 

Hauptner A., 1431 

Hauser T. C., 1106 

Haustermans K., 9, 10, 212, 249, 312, 447, 

527, 1067, 1327 

Hauswald H., 938 

Haverkort M. A., 1052 

Hawkes D., 866 

Hawkins M., 719, 733, 1112, 1139, 1421, 1462 

Hawkins S., 62 

Hawrylewicz L., 1528 

Hay J., 773 

Hayabuchi N., 619, 925 

Hayakawa K., 761 

Hayashi N., 663 

Hayashi Y., 710 

Haydaroglu A., 586, 615, 922 

Haydont H., 178 

Haylock B. J., 634 

Hayran M., 1456 

Heath E., 301 

Hedelin H., 450 

Hedetoft M., 1334 

Hedfors D., 224 

Hedman M., 1480 

Heeg P., 1384 

Heeger S., 884 

Heemsbergen W., 257, 453, 684 

Heeneman S., 289 

Heesters M., 1096 

Hehlgans S., 69 

Height R., 589, 1032, 1134, 1514, 1533 

Heijmen B., 50, 96, 227, 231, 344, 476, 483, 

547, 1156, 1172, 1556 

Heikkonen J., 1443 

Hejazi P., 1265 

Helle S. I., 73 

Hellebust T. P., 122, 174, 554 

Helleday T., 48 

Helyer S., 149, 379 

Hendricks F., 329 

Henke M., 460 

Hennequin C., 270, 1085, 1423 

Henry A., 325, 540 

Herfarth K., 262, 745, 884 

Hermans R., 239, 309, 462 

Hermansson I., 291, 1488, 1503, 1507 

Hermesse J., 1010 

Hermosilla E., 795 

Hermus A., 814 

Hernandez M., 1370 

Heron D. E., 1547 

Herrada J., 1264 

Herrera Martínez F., 768 

Herreros A., 580 

Herrmann T., 153 

Herrup D., 1377 

Hertzman S., 649 

Hessel F., 314, 1479 

Hesselius P., 1480 

Hetnal M., 931 

Heufelder J., 1376 

Heuser M., 1555 

Heyda A., 274 

Heymann M. F., 1482 

Hideghéty K., 584, 693, 1101 

Hill R. P., 22 

Hill S., 471 

Himmelman J., 753, 935 

Hingorani M., 127, 675 

Hintereder G., 1471 

Hipp M., 1153, 1351 

Hirai T., 663 

Hirakawa H., 1127 

Hiromoto M., 1161 

Hirsh A., 1034 

Hirt M., 1387 

Hishikawa Y., 827, 886 

Hitomi J., 591 

Hjelm Skog A. L., 951 

Hjelm-Eriksson M., 451, 991, 993, 994, 1050, 

1078 

Hjelm-Hansen M., 1366 

Hjertnes S., 308 

Ho G., 1112 

Ho K., 815, 1441 

Hoar M., 1526 

Hoban P., 1415 

Hochstenbag M., 115, 116, 893 

Hoebers F., 428 

Hoegele W., 90 

Hoegen-Chouvalova O., 849 

Hoekstra C., 1531 

Hoelscher T., 447 

Hoess A., 884 

Hoffmann A., 310, 455, 536, 544, 1098 

Hoffmans D., 139 

Hofheinz F., 1479 

Hofman P., 1003 

Hofstra S., 1011 

Hogeweg L., 1173 

Hohaus S., 674 

Hoinkis C., 1178 

Hol M., 344 

Hol S., 872, 1367, 1407 

Hollander M., 147, 1347, 1348 

Hollingdale A., 870 

Hollingdale R., 1192 

Hollywood D., 41, 1434 

Holmberg A., 1050 

Holmberg C., 1187 

Holmberg E., 235, 1448 

Holmberg O., 1549 

Holmberg R., 77, 1400 

Holmes C., 62 

Holst-Hansson A., 423 

Holt T., 966 

Homans N., 816 

Honda N., 1108 

Hondo M., 1108 

Honess D., 1439 

Hoogeman M., 50, 242, 547, 816, 1172 

Hoogenraad W., 315 

Hoole A., 1183 

Hoorens A., 711 

Hoornaert M. T., 972 

Hope A., 910 

Horev G., 1501 

Horiot J. C., 315 

Horsman M. R., 129 

Horst A., 300, 1015 

Horst I., 1406 

Horvath G., 753 

Horwich A., 98 

Hoskin P., 3, 471, 564, 1064, 1235 

Hospers G., 271 

Houben A., 313, 914 

Houben R., 115, 253, 665, 1046 

Hounsell A., 877 

Houweling A., 843, 854 

Hovan A., 787 

Hoving S., 289 

Howes N., 955 

Hrbacek J., 219, 1193, 1349, 1398 

Hub M., 465, 521 

Huber P., 884, 938 

Huddart R., 64, 98, 936 

Hudej R., 572 

Hudson E., 187 

Hug E., 240, 294, 655, 949, 1376 

Hug E. B., 292 

Huget P., 727 

Hughes J., 760 

Hughes R., 705 

Hughes S., 866 

Hugon R., 371 

Hugosson J., 1049 

Huguet F., 1423 

Huh H. D., 1221 

Huizenga H., 975 

Hulshof M., 1116, 1169, 1181 

Hultborn R., 654, 753, 1089, 1454, 1464, 1486 

Hulthén M., 784 

Hultman K., 851 

Hultqvist M., 341, 1215 

Humphrey P., 553 

Huq S., 1547 

Hurkmans C., 145, 354, 356, 406 

Hurmuz P., 901 

Husain S., 995 

Hussain R., 774, 821 

Hussain S., 64, 936 

Husson F., 373, 1285, 1321 

Hutnik M., 274, 1087, 1437 

Huyskens D., 1102, 1284, 1399, 1405 

Hwan Kim K., 1290 

Hyeok Jeong D., 1290 

Hynds S., 442 

Hynkova L., 764 

Hysing L., 513 

HyungJun Y., 730 

Hyödynmaa S., 357, 605, 1337 

Höller U., 434 

Høyer M., 1, 117, 332, 523, 1182, 1404 

Iaccarino G., 600 

Ian A. M., 1072 

Iannattone C., 819 

Ibbott G., 439 

Ichimiya Y., 737 

Iconomou G., 956 

Idasiak A., 658, 678, 836, 1365 

Iftner T., 158 

Iftode C., 1016, 1166

AUTHOR INDEX 

Iganej S., 857 

Iglesias García J., 700 

Ijzendoorn van K., 872 

IJzermans J., 231 

Ikeda K., 1490 

Ikeya-Hashizume C., 921 

Iliescu S., 1244 

Ilija V., 1535 

Illidge T., 511 

Ilyas A., 821 

Im S. A., 587 

Imada H., 737 

Imagunbai T., 750 

Imai T., 435, 1158 

Immerzeel J., 1531 

Impens A., 1152 

Inal A., 578 

Inamura K., 1161 

Incrocci L., 421, 476 

Indrieri P., 660, 961, 1082 

Innocente R., 715 

Inomata T., 671, 1024 

Inoue K., 997 

Inoue T., 920 

Installe J., 796 

Ioannis K., 973 

Ionascu D., 546 

Iori M., 29 

Ippolito E., 249, 645, 706 

Ireland R., 916, 1165 

Isacsson U., 860, 1392 

Isambert A., 372, 373, 1285 

Isern J., 1389 

Italiani M., 662 

Itoh S., 591 

Iustin R., 1071, 1075 

Ivaldi G., 1039, 1051 

Ivaldi G. B., 1028, 1054 

Ivashin A., 903 

Iwakawa M., 435 

Iwata H., 921 

Izadi S., 457 

Izewska J., 355, 1211, 1215 

Jaal J., 288 

Jabbari N., 1262 

Jaberi R., 1200, 1277 

Jackson M., 1197, 1467, 1474 

Jacobs F., 543, 1007 

Jacobs I., 1002 

Jacobsson L., 753, 1454 

Jaegle E., 1177, 1202 

Jaffray D., 478 

Jager J., 315, 665 

Jain P., 1138 

Jakse G., 246 

Jalali F., 67 

Jalali R., 1422 

Jamema S., 742 

James H., 82, 804, 1330 

James N., 64, 936 

Jamshed A., 774, 821 

Jan S., 105 

Jancar B., 825 

Jang J. Y., 713 

Jang N., 831 

Jani K., 809 

Janjan N., 966 

Jansen C., 1548 

Jansen E., 186, 1522 

Jansen J., 428 

Jansen N., 1010 

Jansen P., 1011 

Janssen M., 245, 269, 697, 738 

Janssens G., 814, 1137 

Janssens G. O., 254 

Jansson H., 1014 

Jansson M., 224 

Janus C., 1011 

Jarzab M., 1489 

Jasmine Lööf J., 1495 

Jassem J., 524 

Jaworska M., 427 

Jayanti J., 570 

Jaywant S., 1415 

Jedlinski A., 1493 

Jee K., 100 

Jee K. W., 474 

Jefferies S., 84, 633, 945 

Jellvart A., 1486 

Jena R., 84, 633, 1315 

Jend C., 1432 

Jenkins P., 64, 936 

Jensen A., 336, 745 

Jensen A. D., 884 

Jensen A. R., 505 

Jensen H., 137, 753, 1355, 1366 

Jensen H. A., 1099 

Jensen J. K., 999 

Jensen K., 1539 

Jeon B. C., 772 

Jeong Ae L., 807 

Jeong H. S., 828 

Jeong K., 1335 

Jeong Woong P., 885 

Jeraj R., 93 

Jereczek-Fossa B. A., 188, 793, 1028, 1039, 

1051, 1054, 1086 

Jeremic B., 905 

Jerez Sainz I., 1287 

Jerhammar F., 1484 

Jermann M., 1376 

Jerneja M., 1535 

Jeukens C., 1103 

Jeung T. S., 1221 

Jezequel P., 1482 

Jezierska D., 806 

Jezioranski J., 238 

Ji Y. L., 594 

Jiang W., 704 

Jiang Y., 704 

Jimenez E., 646, 672 

Jimenez Lahuerta R., 1551 

Jin J., 681 

Jin-Ho C., 885 

Jingu K., 720, 911, 1031 

Jobsen J., 63 

Jochymek B., 695, 731, 1538 

Joensuu H., 181, 1443 

Johansen J., 817, 1374 

Johanson I., 319 

Johanson V., 1468 

Johansson B., 1012 

Johansson H., 1089 

Johansson K. A., 28, 235, 291, 319, 361, 523, 

598, 1130, 1444, 1448, 1488, 

1503, 1505, 1507, 1510, 1525 

Johansson S., 436, 1549 

Johnsson S., 1516 

Johnston C., 87 

Johnstone P., 1318 

Joiner M., 20 

Jolicoeur M., 1047 

Jones P., 633 

Jongen R., 297 

Joniau S., 1067 

Jonska-Gmyrek J., 940 

Jonsson C., 77 

Jonsson J., 1295 

Joon Hyoek L., 1449 

Joore M., 337, 987 

Joosten H., 231 

Jordan B., 461 

Jordan T., 1373 

Jornet N., 1196 

Joseph D., 452 

Joseph K., 616 

Josifovski T., 717 

Josipovic M., 597 

Joy A., 899 

Joyner M., 1009, 1074 

Ju T., 464 

Juhler-Nøttrup T., 405, 1301 

Julia J. C., 799, 1061, 1340 

Julka P., 741, 766 

Jung H., 1516 

Jung H. W., 653 

Jung K. C., 1450 

Junius S., 1067 

Jurado Bruggeman D., 1353 

Jurado D., 1352 

Jurgenliemk-Schulz I., 756 

Justin L., 1487 

Jánváry L., 1395 

Jäkel O., 225, 1384 

Jüling-Pohlit L., 1471 

Jürgenliemk-Schulz I., 63, 331, 560, 740 

S 503 

Kaanders H., 428, 814, 1098 

Kaanders J., 131, 172, 254, 310, 455, 469, 544 

Kachris S., 917, 952 

Kader H., 773 

Kafrouni H., 1321 

Kagami Y., 761 

Kagawa K., 1158 

Kahan Z., 584 

Kahraman Cetintas S., 614 

Kahu H., 1454, 1464 

Kahveci R., 927 

Kairemo K., 1443 

Kalidien Y., 1113, 1529 

Kalnicki S., 759, 783, 850 

Kam K. L., 837 

Kamada T., 863 

Kamata M., 1490 

Kamensky V., 1438 

Kamer S., 922 

Kamian S., 1409 

Kaminski P., 1226, 1372 

Kamiñski A., 1087 

Kamphuis M., 351, 1142, 1169 

Kampinga H., 261, 1455 

Kamposioras K., 726 

Kan B., 1483 

Kanazawa S., 1161 

Kancherla K., 1026 

Kandatsu S., 863 

Kanematsu N., 297 

Kaneva R., 1459 

Kang H. C., 855 

Kang J., 729, 730, 751, 986 

Kang S. H., 1466 

Kangasmäki A., 1339, 1443 

Kania M., 939, 1226, 1258, 1260, 1261 

Kanikowski M., 596, 824, 1017, 1063 

Kanis B., 1556 

Kantor G., 1391, 1540 

Kappas C., 1248, 1293, 1445 

Kappelle A., 814 

Karabut M., 755 

Karacetin D., 873, 1006 

Karadayi N., 1095 

Karadeniz A., 786 

Karageorgis P., 963 

Karahacioglu E., 1457 

Karaiskos P., 934, 1114 

Karakoyun Celik O., 586 

Karaman S., 873 

Karczewska - Dzionk A., 699 

Kardamakis D., 956, 1470 

Karger C., 262, 465 

Karger C. P., 225, 259 

Karhu-Hämäläinen A., 357 

Kariya S., 591, 997, 1125 

Karlsdottir , 513 

Karlsson A., 299 

Karlsson K., 1179 

Karlsson M., 163, 894, 1240, 1295 

Karlsson P., 235, 319, 598 

Karpienski N., 1406 

Kartal C., 614 

Karthikeyan S., 1196 

Karvat A., 773 

Kashani R., 474, 521 

Kasprowicz A., 562, 1066 

Kassaee A., 778 

Kassim I., 227 

Kataoka M., 761, 867 

Kataoka Y., 591 

Katayama N., 1161 

Kato S., 435, 743, 761 

Katsuoka Y., 1024 

Kattan J., 725 

Kattevilder R., 1531 

Kauppinen J., 1284, 1405 

Kawai T., 921 

Kawczynska M., 1066 

Kawecki A., 839 

Kay I., 995 

Kaya S., 874 

Kaytan Saglam E., 873


Kazemian A., 457, 1409 

Kazemnejad A., 1265 

Kazi R., 847 

Kazmierska J., 250 

Kazmierski M., 250 

Kazumoto T., 761 

Keall P., 52, 78, 141, 477, 875 

Keane G., 878, 1109 

Keaveney M., 1511 

Kecmanovic D., 716 

Kee Kim J., 1290 

Kee Oh Y., 1290 

Keen-Hun T., 452 

Kehl M., 246 

Keisari Y., 563, 574, 1501 

Keisch M., 320 

Keleher A., 320 

Kellas S., 573 

Keller B., 629 

Keller S., 946, 1496 

Kelly C., 878 

Kelly P., 1417 

Kelly V., 101, 1520 

Kelson I., 563, 574, 1501 

Kemikler E., 873, 1204 

Kemikler G., 767, 1246 

Kenjo M., 761 

Kennedy J., 1434 

Kepka L., 897, 1465 

Kerkar R., 744 

Kerkhof E., 132, 331 

Kerr G., 608 

Kerrou K., 1440 

Kessler M., 162, 465, 474, 521 

Kestin L., 324 

Keum K., 904 

Keum K. C., 714, 772, 805 

Keun Chil P., 807 

Kevric M., 1093 

Khaksar S., 976, 1025, 1030 

Khalafi H., 1135 

Khamphan C., 1177, 1202 

Kharchenko V., 903 

Khoo V., 98, 518, 1032, 1048, 1079, 1134, 

1514 

Khullar D., 464 

Kiatsi E., 1359 

Kilciksiz S., 1429, 1477 

Kilic E., 816 

Kim C. S., 855 

Kim C. Y., 736 

Kim D. W., 1461 

Kim G., 734, 1124, 1228 

Kim G. E., 714, 772, 805 

Kim G. J., 907 

Kim H., 1449 

Kim H. J., 1234 

Kim H. S., 1466 

Kim H. Y., 828 

Kim I. A., 1234 

Kim I. H., 653, 666, 859, 1234, 1499 

Kim J., 86, 714, 785, 904, 1124 

Kim J. C., 707 

Kim J. H., 607, 707 

Kim J. S., 1234 

Kim J. W., 772, 805 

Kim K., 587, 679 

Kim K. O., 1466 

Kim M., 729, 751, 986 

Kim S. W., 679 

Kim S. Y., 714, 772 

Kim T. W., 707 

Kim T. Y., 587 

Kim W., 698 

Kim Y., 698, 904 

Kim Y. B., 714, 772, 805 

Kim Y. K., 736 

Kim Y. N., 1335 

Kim Y. S., 707 

Kimmig B., 1058 

Kimstrand P., 1381 

Kinay M., 782 

Kindblom J., 1071 

Kindblom L. G., 1089 

Kinhikar R., 561, 1422 

Kinhult S., 654 

Kipp B., 1390 

Kiprian D., 839 

Kirby A., 1118 

Kirby R., 305 

Kiriaki M., 973 

Kirisits C., 121–123, 175, 280, 283, 739 

Kirkels W., 1011 

Kiseleva E., 755 

Kiyohara H., 743 

Kizaki H., 1158 

Kizir A., 873 

Kjellén E., 361 

Kjær-Kristoffersen F., 142, 405 

Kleiner D., 575 

Kloen E., 218 

Klomp D., 133 

Klotz L., 999 

Knopf A., 490 

Knöös T., 299, 438, 1256 

Ko L., 1154 

Kobayashi M., 694 

Kobayashi T., 663 

Koc M., 1451 

Kocaeli H., 661 

Koch S., 1419 

Koch W., 832 

Kocsis B., 948 

Kodaira T., 761 

Kodama T., 750 

Kodani K., 694 

Koedooder K., 779, 1390 

Koelbl O., 1153, 1351 

Koike I., 920 

Koizumi M., 1083 

Kok J., 132 

Koken P., 223, 1280 

Kolby L., 1468 

Kolios M., 1487 

Kolkman-Deurloo I. K., 354, 1011, 1524 

Kolodziejczyk M., 718 

Komemushi A., 1490 

Komisopoulos G., 1168, 1333, 1375 

Kong F. M., 114 

Kong V., 1412 

Kong W., 353, 946 

Koning C., 779 

Konski A., 687 

Koom W. S., 805 

Kooy H., 498, 1377 

Kopek N., 117 

Kopp P., 892 

Koppe F., 872 

Koptenko S., 99 

Korab-Chranowska E., 638 

Korba A., 1021 

Korcum A. F., 578, 709, 858, 922 

Korevaar E., 144, 1214 

Korf E., 345 

Koritzinsky M., 166, 390, 437, 470, 472 

Kornafel J., 625, 631 

Korogi Y., 737 

Korporaal J., 311, 1103 

Korreman S., 54, 78, 79, 141, 142, 230, 302, 

405, 518, 597, 1301 

Korzeniowski S., 931 

Kosaki K., 663 

Koto M., 911, 1031 

Kotronaki M., 917 

Kotte A., 1171 

Kotzasarlidou M., 1359 

Kotzerke J., 1178 

Koukourakis G., 726 

Koukourakis M., 841, 1475 

Kouloulias V., 726 

Kouri M., 1443 

Koutrouvelis P., 329 

Koutsouveli E., 934, 1114 

Kouvaris I., 781 

Kouwenhoven E., 1113 

Kovacs A., 571, 1123 

Kovacs P., 1216 

Kovács G., 110 

Kovács P., 1329 

Kowalska M., 1489 

Kowalska T., 718 

Kozlowski M., 524 

Kragl G., 55 

Kramar A., 865 

Kranzinger M., 644, 892 

Krause M., 128, 314, 431 

Krawczyk Z., 1489 

Kremensky I., 1459 

Krempien R., 244, 884 

Krengli M., 1117 

Krieger T., 491 

Krishnan S., 245, 269, 876, 1517 

Krishnapuram B., 437 

Kristensen C., 817 

Kristensen I., 1259, 1515 

Kristensen S., 1278 

Kristensen V., 60, 308 

Krivokapic Z., 716 

Kroeber T., 467 

Kroemer G., 126 

Kron T., 541, 1134 

Kruszyna M., 1220 

Krynicki R., 940 

Kræmer K., 1301 

Kröger R., 275 

Kubaszewska M., 596, 824, 1017 

Kubes J., 685 

Kubota K., 591, 1125 

Kucucuk S., 767 

Kudrén D., 556, 1001 

Kuerer H., 320 

Kuipers F., 1393 

Kukolowicz P., 1211, 1356 

Kulig J., 718 

Kulik A., 562, 1066 

Kulik R., 695 

Kulkarni A., 177, 655 

Kulmala A., 1339 

Kumar A., 809 

Kumar M., 741 

Kumar S., 741, 766 

Kumareswaran R., 67 

Kunkler I., 608 

Kunz P., 1102 

Kunz-Schughart L., 1478 

Kuo C., 797 

Kupelian P., 477 

Kurhanewicz J., 376 

Kurihara S., 920 

Kuroda M., 1161 

Kurt I., 588 

Kurt M., 614, 641 

Kurt S., 614, 782 

Kuster N., 1311 

Kutcher G., 618 

Kuten A., 954, 1410 

Kwang Gheol K., 1449 

Kwias Z., 1086 

Kwon E. K., 1450 

Kwon H. C., 1461 

Kyu Chan L., 885 

Kälkner K. M., 451, 559, 929, 991, 993, 994, 

1050, 1078, 1187 

Kêpka L., 1544 

Kýratlý H., 937 

La Sala S., 667 

La Torre G., 268, 352 

Laache M. L. M., 554 

Laberge F., 871 

Lacasse Y., 871 

Lacko A., 625, 631 

Lacko M., 428 

Lackov T., 1459 

Lacornerie T., 691, 845 

Lacruz Bassols M., 1275, 1551 

Lacruz M., 613, 868, 1509 

Laffite J. J., 425 

Lafond C., 1540 

Lagendijk J., 74, 124, 132, 133, 331, 1171 

Lagerlund M., 361, 1516 

Lagerwaard F., 1141 

Lahrmann S., 225 

Lahtinen T., 1319 

Lailas N., 329 

Lainez C., 799, 1061, 1120, 1340 

Laing R., 199, 976, 1025, 1030 

Lakeman A., 72 

Lakosi F., 571, 1123 

Lallement M., 606 

Lalonde R., 1547

AUTHOR INDEX 

Lalondrelle S., 98 

Lam K., 521 

Lamb D., 452 

Lambein K., 237 

Lambert C., 1047 

Lambert J., 1197 

Lambin P., 115, 116, 118, 243, 245, 253, 256, 

269, 285, 297, 306, 313, 334, 

337, 390, 430, 437, 456, 463, 

470, 479, 482, 488, 665, 697, 

732, 738, 865, 876, 893, 900, 

914, 944, 987, 1046, 1137, 1517 

Lamers E., 85, 514 

Lamm I. L., 1043 

Lammering G., 46, 115, 245, 269, 285, 306, 

697, 732, 738, 865 

Land I., 374, 1145 

Landau D., 866 

Landberg T., 1334 

Landoni C., 1022 

Landoni V., 600, 1029, 1056 

Landuyt W., 390 

Lang I., 621 

Lang S., 280, 283 

Lange B., 1512 

Lange D., 427 

Lange M., 150 

Langen K., 477 

Langendijk H., 144, 147, 218, 247, 261, 277, 

278, 297, 322, 849, 1096, 1122, 

1173, 1214, 1342, 1345, 1347, 

1348, 1371, 1419 

Langendijk J., 114, 240, 258, 287, 652, 770, 

967, 1453 

Langenes K., 1525 

Langley B., 1055 

Langley S., 976, 1025, 1030 

Langsteger W., 316 

Lanza Silveri S., 777 

Lanzos E., 626 

Lapadula L., 1323 

Lapeyre M., 360 

Lappi S., 1163, 1362 

Larici A. R., 889 

Larry J., 637 

Larsen A., 1423 

Larsson A., 1516 

Lartigau E., 691, 845 

Larysz D., 658 

Lassalle S., 229 

Lassen P., 458, 459 

Lattuada P., 728 

Lau H., 429 

Laurberg S., 702 

Laurell G., 154, 835, 1446 

Lauriola L., 1492 

Lauterbach M., 978 

Law S., 1197 

Lawford C., 1514 

Lawlor M., 589, 1032, 1514 

Lawrence T., 637 

Lawton C., 38 

Lax I., 134, 395, 523, 1149, 1179, 1273 

Laytragoon-Lewin N., 1425 

Lazzari R., 793, 1039, 1051 

Lebesque J., 72, 233, 257, 392, 453, 478 

Lebschi J. A., 468 

Leclerc M., 871 

Leclercq N., 425 

Lee A. W. M., 837 

Lee C., 904 

Lee C. G., 772, 805, 1335 

Lee D., 729, 730, 751, 904, 986 

Lee D. H., 707, 714, 772 

Lee E. Y., 1466 

Lee H. S., 1461 

Lee I., 637, 904 

Lee I. J., 805, 1335 

Lee J., 97, 412, 461, 666, 688, 738 

Lee J. A., 49, 56 

Lee L., 815, 1138 

Lee M. Y., 698 

Lee N. K., 736 

Lee R., 1357 

Lee S., 736, 1221, 1228 

Lee S. H., 885, 1221, 1450 

Lee S. W., 707 

Lee T. H., 734 

Leek H., 1043 

Leemans C., 278 

Leemans R., 277 

Leer J. W., 40, 967 

Lees-Miller S., 429 

Lefaix J. L., 943 

Lefebvre J. L., 195, 845 

Lefkopoulos D., 1285 

Lei M., 776, 780 

Lelie S., 135 

Lemanski C., 65 

Lembke I., 1058 

Lencart J., 1194, 1201 

Lengyel E., 1476 

Lennernäs B., 450, 1049, 1071, 1075, 1448 

Leon D., 701 

Leone M., 590, 1111 

Leong C., 773 

Leroux T., 81 

Lerut E., 1067 

Leslie F., 1048 

Lester F., 187 

Leszczynski K., 1140 

Leszczyñski W., 731 

Leszek M., 1346 

Leteur C., 126 

Leutenegger E., 1085 

Levendag P., 50, 231, 242, 816, 902, 1156, 

1311 

Levernes S., 444 

Levin N., 523 

Levin W., 238, 1520 

Levitt S., 451, 994, 1050, 1075 

Lewensohn R., 523 

Lewin F., 842, 1425 

Lewis G., 471 

Lewis N., 687 

Lhommé C., 193 

Li J., 704 

Li L., 23 

Li M., 978 

Li N., 681 

Li T., 681, 687 

Li X. M., 594 

Li Y., 681 

Liang J., 293 

Liang S., 1447 

Liao J., 234 

Liberopoulou G., 726 

Licitra L., 155, 194 

Licznerska E., 1220 

Lievens Y., 548, 865, 876, 923, 1326, 1349 

Lim Joon D., 1032, 1048, 1079, 1134, 1514 

Lim Joon M., 1048 

Lim K., 101 

Lim S., 1221, 1228 

Lin B., 1133 

Lind B., 226, 282, 605, 835, 888, 1328, 1333, 

1337, 1379, 1442, 1446 

Lind H., 282, 307, 762, 1444 

Lindberg A., 1299 

Lindegaard J. C., 303, 480, 702, 1254 

Lindegren S., 753, 1454 

Lindell T., 556 

Lindencrona U., 935, 1473 

Linder J., 1075 

Lindholm C., 361 

Lindner B., 940, 1544 

Lindsay R., 136, 1157 

Lindskog M., 1132 

Ling C., 17 

Linthout N., 135, 525 

Liposits G., 1216, 1329 

Lips I., 1023 

Lisbona A., 794, 798, 1231, 1363, 1391 

Litoborska J., 1220 

Litoborski M., 1220 

Litt H., 234 

Littera A., 1117 

Littler J., 89 

Litzenberg D., 100 

Liu A., 333 

Liu D., 92 

Liu J. J., 594 

Liu M., 1278 

Liu T., 618 

S 505 

Liu T. F., 156 

Liu X., 681 

Liu Y., 342, 681, 1133 

Livi L., 620 

Livsey J., 984 

Lliso F., 1396 

Lobato Busto R., 612 

Lobato Muñoz M., 1287 

Lobo J., 1286 

Locatelli F., 690, 692 

Loeschel R., 90 

Loffeld S., 1046 

Logue J., 984, 1000 

Lohr F., 94, 1401 

Lohuis P., 289 

Loi G., 1117 

Loiseau H., 1391 

Lomax A., 180, 240, 292, 294, 297, 340, 949 

Lombaert I., 1455 

Lombardi D., 422 

Long C., 1447 

Long M., 1462 

Lonneux M., 49 

Loo S., 791, 818, 826 

Loorents V., 851 

Lopes M. D. C., 1224, 1269, 1281 

Lopes S., 349, 1532 

Lopez - Vilanova N., 1190 

Lopez Carrizosa M. C., 771, 869, 959 

Lopez Guerra J., 868 

Lopez J. L., 613, 947, 1509 

Lopez M., 676 

Lopez Medina A., 1370 

Lopez Muñoz M., 891 

Lopez R., 811 

Lord H., 130 

Loreggian L., 276 

Lorentzen H., 1151 

Loreti F., 656 

Lortlar Ucankus N., 1457 

Loscos S., 1190, 1338, 1340 

Lotz H., 560, 1169 

Louis-Belle N., 565 

Louvet C., 1423 

Lovey J., 680, 1076 

Low D., 464 

Lozano A., 1426 

Lozano E., 1128 

Lozano Galan J., 964, 1105, 1551 

Lozano J., 613, 868, 947, 1275, 1509 

Lu H. M., 1377 

Lu L., 464 

Lucchini A., 918 

Luchin Y., 1378 

Lucia M., 449 

Luciana R., 1508 

Lucio F., 1203 

Luetgendorf-Caucig C., 664 

Lugagne P. M., 1085 

Luijten P., 133, 311 

Lukas P., 1361 

Lukaszczyk-Widel B., 274 

Luna Vega V., 612 

Lund E., 1255 

Lund J. A., 523 

Lundell G., 451, 991, 993, 994, 1078 

Lundell M., 451, 557, 951, 991, 993, 1078, 

1187, 1218, 1343 

Lundgren J., 1425 

Lundgren L., 654 

Lundh C., 935, 1473 

Lundin A., 101 

Lundqvist C., 649 

Lundstedt D., 235 

Lundström A., 935 

Luo J., 810 

Luo S., 1211 

Lupattelli M., 426, 965 

Lupton S., 822 

Lusinchi A., 360 

Luster M., 209 

Lutgens L., 63, 285, 732, 758 

Lutters G., 1274, 1555 

Luzi S., 706, 1070, 1081 

Lyczek J., 562, 1066 

Lynch A., 1183 

Lynch T., 877


lYoo S., 730 

Lyraraki E., 917, 952 

López Guerra J. L., 1105 

López J. L., 964 

López López R., 700 

López Morones R., 358 

López Muñóz M., 1065 

López Soler F., 1013 

López Vilanova N., 1338 

López-Soler F., 1131, 1364 

Lödén B., 361 

Löffler H., 1427 

Löfroth P. O., 1041 

Löfvenberg R., 1089 

Maass A., 1345 

Mac Manus M., 413 

Macchia G., 102, 236 

MacDougall H., 1485 

Macedo S., 1552 

Machulla H. J., 468 

Machánová M., 1073 

Macia M., 701 

Macias Hernandez V., 1504 

Maciejewski B., 274, 1465, 1489, 1544 

Mackay R., 1463 

Mackenzie C., 317 

Mackie T., 62, 416 

MacKillop W., 214, 353, 506, 508, 946, 1491, 

1496 

Macq B., 97 

Macías Hernández V., 926, 1005, 1097 

Madani I., 25, 297, 775 

Madon E., 667, 763, 953, 1386 

Maduro J., 144, 147, 1371 

Maes F., 249 

Magagnin M., 437 

Magee D., 1157 

Maggi F., 889 

Maggiulli E., 1176 

Magli A., 1119 

Magliocco A., 429 

Magnander K., 1464 

Magné N., 284, 757, 1251 

Magri C., 633 

Magrini S., 290, 965 

Mah D., 759 

Mahantshetty U., 724, 744 

Mahata A., 1229 

Mahe M. A., 794, 1018 

Maheshwari A., 744 

Mahmood Reza A., 1277 

Mahé M. A., 1391, 1482 

Mai S., 94, 1401 

Maier S., 294 

Maigne L., 1267 

Maingon P., 210, 360, 518, 1102 

Mainwaring K., 1373 

Maisonobe T., 943 

Majeed U., 774, 821 

Majewski W., 427, 1100, 1528 

Major T., 569, 680, 834, 1076, 1395 

Majunder K., 450, 1049 

Makar A., 237 

Makridou A., 1359 

Malandain G., 372, 1309 

Malatara G., 1470 

Maldonado J., 646, 672 

Malecki K., 931 

Malet M A., 1097 

Malicki J., 1378, 1541, 1553, 1554 

Malik Z., 89, 996 

Malinen E., 1175 

Malisan M. R., 1119 

Mallick S., 724 

Malmström P., 235, 598 

Malusecka E., 1489 

Maluta S., 673 

Mameli A., 1185 

Mammar H., 1440 

Mamon H., 546 

Manchul L., 238, 1520 

Mandall P., 1064 

Mandeville H., 471 

Mandoliti G., 970, 971 

Manfrida S., 352, 632, 645, 674, 930, 969, 

1492 

Mangel L., 1216, 1329 

Mangili P., 980 

Mangiola A., 632 

Maniakowski Z., 1258 

Manigandan D., 1196 

Mannocci A., 352 

Mans A., 221, 350, 481, 1227 

Mantini G., 632, 645, 712, 819, 889, 969, 

1070, 1081, 1358, 1492, 1506 

Mantle C., 1048 

Mantovani C., 1452 

Mantovani L., 1188 

Mapelli M., 640 

Marafioti L., 426 

Maranzano E., 426, 656, 662, 669, 970, 971 

Maravelis G., 726 

Marazzi F., 819 

Marcelino C., 1532 

Marchand V., 1018, 1540 

Marchant T., 815 

Marchesi V., 1321 

Marchetto F., 1244 

Marcié S., 689, 1309, 1394 

Marczak L., 1436, 1437 

Margaritora S., 889 

Margolin G., 557 

Marguet M., 1177, 1202 

Mari C., 908, 998 

Marienhagen K., 642 

Marijnen C., 211, 271, 304, 354, 684, 962 

Marijnissen H., 344 

Marin A., 676 

Marinelli A., 1212 

Marino L., 1506 

Marinone C., 918 

Mark R., 327, 603, 604, 650, 933, 1037, 1038 

Markiewicz I., 1226 

Marlowe C., 861 

Marmiroli L., 590, 970, 971, 1111 

Marosi C., 664 

Marquez M., 1050 

Marrazzo L., 338 

Marruecos J., 1353 

Marsden P., 1439 

Marsella A., 248 

Marsh D., 88 

Marshak G., 1501 

Marshall A., 822 

Martel-Laffay I., 270 

Martelli O., 840, 882 

Martenka P., 806, 1553, 1554 

Martignano A., 1225 

Martijn H., 271 

Martin Angulo M., 676 

Martin C., 791, 818, 826 

Martin L., 360 

Martin Martin M., 676 

Martin S., 871 

Martindale C., 1500 

Martinez A., 324, 1080 

Martinez E., 879 

Martinez F., 580 

Martinez M., 879 

Martinive P., 489 

Martinou M., 1470 

Martorana G. E., 819 

Martínez D., 1550 

Martínez-Möller A., 95 

Marucci L., 853 

Marur S., 832 

Marvin K., 324 

Marzi S., 853, 1029, 1056 

Maráz A., 693, 1101 

Masataka O., 1161 

Masayuki B., 297 

Mascarin M., 422 

Masi L., 912 

Masini L., 1117 

Maslennikova A., 755, 1438 

Massaccesi M., 889, 1506 

Masson-Côté L., 898 

Mast M., 166, 407, 1529 

Masterson-McGary M. E., 1253 

Mastrigt van G., 865 

Matei V., 1039, 1051 

Matei V. D., 1028, 1054 

Mateus J., 1269, 1313 

Matkowski R., 625, 631 

Matos A., 1224 

Matsufuji N., 297, 863 

Mattana F., 640 

Matthews D., 62 

Matthews J., 452 

Mattiucci G. C., 244, 268, 352, 645, 706, 712, 

833, 1070, 1081, 1358 

Mattsson S., 1382 

Maughan S., 187 

Mauri D., 726 

Mavroidis P., 226, 342, 605, 835, 888, 934, 

1040, 1114, 1136, 1168, 1174, 

1328, 1333, 1337, 1375, 1379, 

1403, 1442, 1446, 1469 

Mawdsley S., 705 

Maxwell R., 1439 

Mayadagli A., 651, 1095 

Mayles H., 1222, 1330 

Mayles P., 1211, 1222 

Mazal A., 297 

Mazeron J. J., 1540 

Mazeron R., 958 

Mazonakis M., 917, 952, 1294 

Mazur M., 1372 

Mazzarella G., 590, 1111 

Mazzeo E., 249, 930, 969, 1070, 1081, 1358 

Mazziotta M., 1323 

Mañas A., 1129 

McAleese J., 877 

McArdle O., 657, 960 

McCabe A., 108, 1306, 1312 

McCafferty B., 1109, 1511 

McCall K., 93 

McCaron J., 1394 

McCartan J., 1511 

McCavana P., 1417 

McClean B., 1417 

McClelland J., 866 

McCloy R., 1109, 1511 

McColl G., 544 

McCollom C., 1526 

McDermott L., 170, 221, 350, 481, 1227 

McDonnell D., 87 

McDonnell J. D., 358 

McDowell D., 1434 

McElroy A., 1045 

McGarry M., 87, 657, 960 

McKay M., 176 

McKenna G., 16 

McKenzie D., 1197, 1467, 1474 

McKenzie M., 1357 

McMichael D., 635 

McNair H., 98, 149, 228, 391, 518, 1184, 1421 

McNamara J., 1032, 1079 

McNee S., 915 

McQuade C., 432 

McShan D., 100, 474 

Meder J., 939 

Medin J., 78, 142, 1527 

Meduri B., 889, 1506 

Meersschout S., 876 

Meertens H., 240, 247, 287, 1173, 1342, 1419 

Mehrara E., 1468 

Mehta M., 93, 396 

Meier M., 1512 

Meigooni A., 184 

Meinzer A., 467 

Meis-Kindblom J. M., 1089 

Meissner W., 718 

Meister M., 524 

Melcher A., 675 

Melchor M., 1550 

Mele M. C., 819 

Melhus C., 125, 1250, 1282, 1283 

Melo M., 566 

Membrive Conejo I., 947, 1551 

Membrive I., 613, 868, 964, 1105, 1275, 1389, 

1509 

Mendenhall W., 830 

Mendez Romero A., 231 

Mendicote F., 1128 

Mendonca V., 659 

Menegakis A., 431 

Menegalli-Boggelli D., 1363 

Menegotti L., 454, 1004, 1042, 1225, 1369 

Meng J., 1305

AUTHOR INDEX 

Menichelli C., 912 

Mens J. W., 63, 547, 758, 1143, 1172 

Menten J., 517 

Mentha G., 682 

Meral R., 786 

Mercke C., 361, 929, 951, 1146, 1480 

Mercke C. E., 557 

Mercuri A., 1032, 1048, 1079 

Meregalli M., 690, 692 

Merks H., 779 

Merkx M., 310 

Merkx T., 814 

Meropol N., 687 

Merrick S., 542, 978, 1055 

Merron A., 127 

Mertens I., 212, 249 

Mervoyer A., 794, 798, 1391 

Merz F., 644, 892 

Mesia R., 1426 

Messa C., 1022 

Messai T., 284, 924 

Messaï T., 193 

Messina F., 908, 998 

Messing E., 449, 1057 

Metaxas M., 579 

Metz J., 735 

Mewes A., 1413 

Mexner V., 392 

Meyer J. E., 797 

Meyer T., 995 

Mezo T., 584 

Miah A., 733, 846 

Miccichè F., 645, 777, 819, 1506 

Micev M., 716, 717 

Michael L., 968 

Michalaki V., 781 

Michalschi W., 940 

Michalski W., 839 

Michele M., 1508 

Michieli M., 422 

Michiels C., 489 

Michimoto K., 694 

Mignogna M., 426 

Mihai A., 1547 

Mihaylova I., 748 

Mijnheer B., 221, 350, 440, 479, 481, 482, 488, 

518, 1227, 1545 

Milanesi I., 1430 

Milecki P., 1086 

Miles E., 82 

Miliadou A., 726 

Milind K., 766 

Milker-Zabel S., 515, 938 

Millar J., 1044 

Miller C., 1498 

Miller D., 345 

Miller G., 449 

Miller N., 1434 

Mills J., 374, 1145, 1206 

Milosevic M., 101, 238, 1520 

Milross C., 1467 

Mimura M., 921 

Min C., 1124, 1228 

Min C. K., 734, 907 

Mineo T. C., 890 

Minguez J., 879 

Minissale A., 1054 

Minkema D., 145, 602, 1150 

Minken A., 1531 

Minohara S. I., 863 

Minoru U. M., 1072 

Minvielle S., 1482 

Mirabel X., 65, 691, 845 

Mirada A., 582, 626 

Miralbell R., 315, 636 

Miralles L., 1129 

Mirimanoff R. O., 315, 378 

Mirri M. A., 965 

MiSook K., 730 

Miszczyk L., 427, 658, 678, 695, 983, 1100, 

1365, 1528, 1538 

Misztal L., 617, 1528 

Mitchell D., 984, 1000, 1027, 1064 

Mitera G., 146 

Mitine C., 972 

Mitra S., 570 

MItsumori M., 1083 

Mitsuya M., 911 

Mitusuya M., 1031 

Miyamoto T. A., 863 

Miyatake K., 591 

Miyawaki D., 827, 886 

Miyazaki S., 720 

Mizoe J. E., 863 

Modi P. R., 941 

Modolell I., 701 

Moerland M., 124, 560 

Moerland R., 279 

Mohammad Hosein Z., 1277 

Mohammadi E., 1409 

Mohammed N., 864 

Moinuddin S. A., 88 

Moiseenko V., 787, 830, 861, 1278, 1357 

Mojahed M., 457 

Mok H., 23 

Mokhtari K., 1440 

Molenaar R., 251 

Molls M., 883, 1431 

Moman M., 989 

Moman M. R., 74, 124 

Monari F., 840, 882 

Monetti U., 667, 763, 953 

Monica S., 105 

Monjazeb A., 329 

Monroy Anton J. L., 891 

Monroy J. L., 1065 

Montagna A., 1323 

Monteiro Grillo I., 443, 659 

Montgomery P., 791, 818 

Monti A., 356, 454, 1004, 1042 

Montoto-Grillot C., 270 

Moody M., 432 

Mooi W., 524 

Mooij J. J., 1096 

Moon Seok C., 1449 

Moonen L., 326 

Moore C., 815 

Morales E., 1245 

Morales J., 358 

Morandini G., 276 

Moreno L., 1532 

Moretones Agut C., 701 

Moretti E., 1119 

Morgan A., 108, 1104, 1271, 1310, 1324 

Morgan D., 315 

Morgan S., 579 

Morgan V., 1118 

Morganti A. G., 102, 236, 244, 706, 712, 1081, 

1185, 1492 

Morhed E., 523, 860, 1392 

Mori Y., 663 

Moriarty M., 960 

Morrow S., 373, 1285 

Mosch B., 314 

Moseley J., 101 

Moser T., 262 

Mosleh-Shirazi A., 516 

Mousa A., 1326 

Movsas B., 92, 114 

Moya L. M., 799, 1061, 1338, 1340 

Muanza T., 1126 

Mucha-Malecka A., 427 

Mueller L., 1244 

Muffett L., 633 

Muijs C., 258 

Muirhead R., 915 

Mujcic H., 390 

Mukherjee S., 187 

Mulder H., 1345 

Muldoon C., 1434 

Muley T., 524 

Mullaney L., 87, 539 

Mulè A., 889 

Mumot M., 1378 

Munck af Rosenschöld P., 1043, 1256, 1259, 

1515 

Munck-Wikland E., 810 

Mundt K., 126 

Munos C., 794, 1018, 1231 

Munoz F., 1166 

Munoz Hernandez F., 1016 

Munoz Montplet C., 1352 

Munro A., 703, 1485 

Mur E., 747 

S 507 

Murakami M., 827, 886 

Murata R., 129 

Murcia - Mejia M., 926 

Muren L. P., 73, 166, 232, 332, 513, 1148, 

1182 

Murillo M. T., 626 

Murray B., 1154 

Murray D., 208 

Murrer L., 488 

Musat E., 315, 356 

Muscat S., 915 

Musgrove J., 1264 

Musi G., 1028, 1039, 1051, 1054 

Musielak A., 1537 

Muskett N., 1167 

Muslimovic A., 1486 

Musmacher J., 575 

Mussano A., 667, 763, 953 

Mussari S., 1369 

Mutanga T., 96, 476 

Muti M., 662 

Mutic S., 464 

Muto P., 1508 

Mutyala S., 759 

Muñoz C., 1353 

Muñoz V., 1370 

Myrland L., 1424 

Mäding P., 314 

Ménard C., 1412 

Möller-Levet C., 1498 

Møller I., 957 

Müller M., 1130 

Münter M. W., 884 

N’Guyen D., 1177 

Nachat M., 928 

Nackaerts K., 923 

Nadal A., 708 

Nafteux P., 923 

Nagy T., 680 

Nagy V., 1494 

Nagy Z., 693, 1101 

Nahum A. E., 29, 31, 89, 107 

Nair M., 327, 603, 604, 650, 933, 1037, 1038 

Nairz O., 644, 892 

Nakagawa K., 990, 1322 

Nakajima M., 863 

Nakamura K., 1083 

Nakano T., 743 

Nakata E., 1031 

Nakatani K., 1125 

Nakawatari M., 435 

Nakayama H., 710, 721 

Namysl-Kaletka A., 567, 568, 678 

Nappi A., 942 

Narabayashi I., 671 

Narasaki K., 911 

Narazaki K., 1031 

Nardiello B., 1111 

Nardone L., 674, 819, 1506 

Nasonova E., 1481 

Nasr E., 725 

Nasr F., 725 

Naum P., 1487 

Nava S., 640 

Navalpotro B., 708 

Navarria P., 728 

Navarro Bergadà A. V., 891, 1065 

Navarro V., 701 

Nechelput S., 1152 

Neefjes J., 509 

Negreanu C., 340 

Nehme - Nasr D., 725 

Neijenhuis S., 66 

Nekolla S., 95 

Nelson S., 62 

Nelson V., 1247 

Nemoto K., 720 

Nemoz C., 346 

Neto C., 1406 

Neubeck A. M., 556 

Neufeld E., 1311 

Neumann T., 327, 603, 604, 650, 933, 1037, 

1038 

Neves A. J., 1281 

Nevinny M., 1361 

Newbold K., 792, 846


Neybuch Y., 972 

Ng W. T., 837 

Nguyen D., 1202 

Nguyen G., 300, 1015 

Nguyen L., 318 

Nguyen T. B., 1077 

Nguyen T. V., 1047 

Niazi T., 1126 

Nicholas G., 610 

Nickers P., 1010 

Nickles J., 93 

Nicolini G., 79, 106, 140, 335, 1199 

Nicolotti N., 268 

Nieder C., 369, 642 

Niehoff P., 44 

Nielsen M., 302, 895, 1099, 1355 

Nielsen S., 480 

Nielsen S. K., 303, 702, 1254 

Niemantsverdriet M., 261 

Niemec M., 940 

Niemiec M., 1544 

Niessen H., 390 

Nieves M., 255 

Niibe Y., 761 

Nijkamp J., 304, 330 

Nijman R., 992 

Nijsten S., 482 

Nikapota A., 705 

Nikiel B., 427 

Nikiforidis G., 1446 

Niklinski J., 524 

Nikoghosyan A., 1481 

Nikolaeva E., 903 

Nikolenyi A., 584, 693 

Nikolényi A., 1101 

Nill S., 138, 263, 884 

Nilsson G., 1222 

Nilsson J., 451, 557, 991, 993, 1078, 1187, 

1218 

Nilsson K., 523, 860, 1392 

Nilsson M., 1473 

Nilsson O., 1502 

Nilsson P., 361, 598, 894, 1014, 1256 

Nilsson S., 450, 991, 993, 994, 1075, 1078 

Nioutsikou E., 228 

Nisbet A., 1192 

Nishimura K., 1108 

Nishioka A., 591, 997, 1125 

Nitti D., 715 

Niyazi K. M., 484 

Noack R., 286 

Nobes J., 976, 1025, 1030 

Noe K., 1180 

Noel A., 1321 

Noever I., 816 

Nogués X., 964 

Noh D. Y., 587 

Noh J., 828 

Nord J., 1317 

Nordell B., 1343 

Nordström F., 78, 1243, 1549 

Nori D., 797, 1034 

Norum J., 642 

Nout R., 63, 354 

Novaes P., 566 

Novaes P. E., 808 

Novak J., 778, 790 

Novelli E., 640 

Novotny T., 764 

Nowacki M., 718 

Nowak P., 231, 816 

Nowakowska E., 806 

Nowicka E., 1436 

Nulens A., 1303, 1326 

Nussen S., 246 

Nutting C., 82, 532, 792, 846, 847 

Nuver T., 223 

Nuyts J., 9, 312 

Nuyts S., 32, 239, 309, 462 

Nuyttens J., 50, 242, 271, 398, 902 

Nuñez A. T., 1062 

Nyberg U., 307, 762 

Nygaard D. E., 230, 1301, 1527 

Nyholm T., 163, 1295 

Nyman H., 1411 

Nyman J., 291, 523, 1488, 1503, 1505, 1507 

Nyqvist J., 154 

Nysten S., 479 

Näfstadius P., 77, 1400 

Németh I., 693 

Nörtersheuser T., 1413 

O Hara T., 539 

O’Byrne K., 1434 

O’Connell M. E. A., 776, 780, 812, 813 

O’Doherty M., 1439 

O’Grady S., 1045 

O’Neill A., 216 

O’Neill L., 57, 539, 1511 

O’Neill P., 485 

O’Shea C., 1045 

O’Shea E., 87, 539, 1109, 1511 

O’Sullivan B., 86, 196, 785 

O’Sullivan J., 877 

O’Sullivan N., 829 

Oberascher G., 644 

Oberhammer P., 985 

Oberna F., 834 

Oborska-Kumaszynska D., 1258 

Ochman M., 625 

Oda K., 663 

Oda Y., 827, 886 

Oddstig J., 1502 

Odier L., 958 

ODwyer P., 735 

Oei B., 315, 1548 

Oeksuez M., 1106 

Oelfke U., 138, 263, 297, 301, 336, 518, 520 

Oellers M., 118, 306, 697, 738 

Offermann C., 118, 463 

Offersen B., 599 

Ogawa K., 1083 

Ogawa T., 694 

Ogawa Y., 591, 720, 911, 997, 1031, 1125 

Ogino H., 921 

Ogino I., 920 

Ogo E., 619, 925 

Oguchi M., 761 

Oh D. Y., 587 

Oh S. H., 855 

Oh Y. K., 713 

Ohara K., 721 

Ohguri T., 737 

Ohlson B., 319 

Ohneseit P., 1427 

Ohno H., 1108 

Ohno T., 435, 743, 761 

Ohtomo K., 990, 1322 

Ok Bae K., 607 

Okada T., 1108 

Okamoto A., 1083 

Okano Y., 990, 1322 

Okker J., 1397 

Oksefjell H., 554 

Okutan M., 1204 

Oldenburger F., 254 

Oledzki J., 718 

Olejniczak K., 1537 

Olejnik P., 731 

Olesen T. K., 999 

Olevik Dunder M., 1146 

Oliveira A., 1552 

Oliveira M., 1552 

Olivera G., 143, 416 

Olivotto I., 152 

Olofsen-v.Acht M., 354 

Olofsson J., 163, 1240 

Olofsson U., 235, 1444 

Olsen D. R., 359 

Olsen J. T., 444 

Olsen M., 230 

Olsson A., 1151 

Olsson C., 1444, 1510 

Omeroglu S., 1457 

Omura M., 920 

Oncel M., 1483 

Ondrova B., 764 

ONeill B., 272 

Onelöv E., 282, 762 

Onishi H., 1083 

Op de Beeck B., 711 

Op de beeck K., 462 

Opgård A. M., 1424 

Opolon P., 126, 290 

Oral E. N., 873 

Orban de Xivry J., 1137 

Ordeanu C., 1494 

Orecchia R., 793, 1028, 1039, 1051, 1054, 

1414 

Oria E., 811 

Oritate T., 990, 1322 

Orlova A., 1438 

Orosz Z., 680 

Ors Y., 1477 

Ortega A., 646 

Ortiz Lopez P., 358 

Orton C. J., 169 

Orun O., 1483 

Osada H., 1108 

Oshiro Y., 710, 721 

Osiadacz W., 939 

Osman S., 1156 

Ost P., 1007 

Otsuka S., 921 

Ott O. J., 43 

Ottosson R., 299 

Ottosson W., 601, 1205, 1243 

Ouhib Z., 1341 

Ouyang I., 92 

Overgaard J., 129, 165, 456, 458, 459, 504, 

817 

Overgaard M., 599, 817 

Overweg J., 132 

Owen R., 541, 850 

Oyen R., 1067 

Oyen W., 310, 455, 1098 

Ozbay I., 767 

Ozden S., 1095 

Ozdogan M., 709, 858 

Ozgen S., 651 

Ozgen Z., 651, 1095, 1483 

Ozkan L., 614, 823 

Ozsaran Z., 586, 615, 754, 765 

Ozseker N., 651, 1095, 1483 

Ozturk D., 1385 

Ozturk H., 661 

Ozyigit G., 577, 901 

Ozyurt H., 651, 1483 

Paccagnella A., 276 

Pacheco A., 1253 

Padovani R., 1119 

Padín V. E., 328 

Paesmans M., 425 

Paganetti H., 295, 490 

Paiusco M., 29 

Paiva J., 647, 648, 670 

Pak Y., 922 

Pal N., 951 

Palacios M., 1207 

Palanco-Zamora R., 1273 

Palazzi M., 673 

Palazzolo C., 970, 971 

Paliwal B., 416 

Palm A., 1299, 1444 

Palm S., 753 

Palm , 1189 

Palma-Copete J. D., 1364 

Palmans H., 83, 204 

Palombarini M., 840, 882 

Paludan M., 117, 523 

Paluszczyszyn D., 374 

Panettieri V., 1273 

Pang B., 509 

Panizzoni G. A., 908, 998 

Panousaki K., 963 

Panshin G., 903 

Panteliadou M., 841 

Pap E., 1033 

Papachristofilou A., 883 

Papadopulos S., 358 

Papagiannis P., 120 

Papanastasiou K., 928 

Papanikolaou N., 220, 342, 593, 605, 888, 

977, 1009, 1040, 1074, 1114, 

1133, 1136, 1168, 1174, 1195, 

1232, 1297, 1333, 1336, 1337, 

1375, 1403, 1418, 1469 

Papiez E., 1186 

Papiez L., 1307 

Paprota K., 718

AUTHOR INDEX 

Paradelo J., 449 

Paramerits I., 1293 

Parashar B., 797, 1034 

Paredes A., 879 

Parikh P., 464 

Park C. I., 831, 855, 859, 1499 

Park C. K., 713 

Park H. J., 688 

Park J. M., 1234 

Park S. H., 1221 

Park S. J., 546 

Park W., 828 

Park Y. G., 1234 

Park Y. J., 736 

Parker B., 788 

Parker W., 348 

Parliament M., 1154 

Parodi K., 490, 1384 

Parplys A. C., 1432 

Parraga A., 97 

Partridge M., 1472 

Parvanova V., 748 

Parvis G., 918 

Pasinetti N., 290 

Pasini D., 352 

Pasqualetti F., 639 

Pasquie I., 1231 

Pasquino M., 454, 1004, 1042 

Passoni P., 244 

Patel R., 809 

Patra N., 570 

Patriccioli S., 645, 833, 1358 

Patriksson M., 538 

Patterson H., 305, 1167 

Patterson M., 338 

Pattynama P., 242 

Paul A., 62 

Paul R., 1439 

Paula W. R., 1072 

Paulides M., 1311 

Paulsen F., 1106 

Paumier A., 924 

Pearson A., 71 

Pearson D., 62 

Pearson S., 910 

Pedersen A., 393, 597, 1301 

Pedersen A. N., 230, 405 

Pedersen J., 332 

Pedersen K., 957 

Pedicini P., 1508 

Pedro A., 1061, 1120, 1190, 1338, 1340 

Pedro Olive A., 799 

Pedroli G., 1414 

Pedroni S E., 292 

Peerlinck I., 127 

Peeters A., 337, 987 

Pehlivan B., 949 

Peiffert D., 65, 323 

Pelaez S., 1352 

Pellegrini R., 1322 

Pellizzon A., 808 

Peltola J., 1317 

Pemberton L., 1138 

Penninckx F., 9, 312 

Penninkhof J., 1143, 1212 

Pentimalli S., 728 

Pera J., 328 

Peratoner L., 422 

Perazzini L., 1163, 1362 

Perde M., 1494 

Pereira A., 1194, 1201 

Pereira J. C., 1406 

Pereira L., 1194 

Pereira P. P., 358 

Perez Casas A. M., 879 

Perez L. M., 585 

Perez Romasanta L. A., 1128 

Perez Vara C., 869 

Perez-Calatayud J., 120, 125, 565, 1198, 

1224, 1250, 1282, 1283, 1341, 

1393, 1396 

Perez-Rozos A., 1287 

Pergolizzi S., 426, 970, 971 

Perk L., 256 

Perlman S., 93 

Perman M., 319 

Perna L., 981, 1008 

Peroni C., 1244 

Perrone F., 639 

Perry L., 984 

Persoon L., 245, 269, 479 

Persson B. E., 999 

Persson C., 1012 

Persson E., 1239 

Persson G., 78, 141, 230, 597, 1301 

Peschke P., 259 

Pesko P., 717 

Petazzi E., 1028 

Peterse H., 622 

Petersen C., 467 

Petersen J., 117, 513, 1404 

Petersen J. B., 1148 

Petersson F., 810 

Petillion S., 219 

Petinellis E., 917 

Petinelly E., 952 

Petit A., 1391 

Petit S., 118, 463, 482, 944 

Petkova E., 748 

Petoukhova A., 1113, 1212, 1529 

Petric P., 280, 572 

Petrone A., 590, 1111 

Petrongari M. G., 248, 1029, 1056 

Pettersson A., 1012 

Pettersson N., 1130, 1448 

Petzer A. L., 316 

Peutz-Kootstra C., 428 

Pezner R., 333 

Peña M. J., 964 

Pfannenberg C., 1106 

Pfeffer R., 623, 1304 

Pfeifer D., 1495 

Pharoah P., 433 

Philippe F., 12 

Philippens M., 74, 311 

Picchio M., 468, 1022 

Picken G., 804 

Piera V., 964 

Pierelli A., 296 

Piergentili M., 950 

Piermattei A., 102, 236, 1185 

Piernicola P., 1323 

Piersma H., 223 

Piert M., 411, 468, 637 

Pieters B., 1052, 1390 

Pieterse A., 962 

Pietrowska M., 1436, 1437 

Pietrzak L., 696, 722 

Pignol J. P., 146, 152, 629, 1279 

Pignon T., 360 

Pijls R., 488 

Pijls-Johannesma M., 285, 297, 337, 456, 732, 

865, 900, 987, 1046 

Pilecki B., 274, 1087 

Pimentel Batel V. I., 1249 

Pinelopi G., 973 

Pinezi J., 670 

Pinkawa M., 246 

Pinnaro P., 600 

Pintado D., 1128 

Pinto V., 1194 

Pioli F., 673 

Piotrkowicz N., 1066 

Piotrowski T., 699, 1063, 1314, 1331 

Piro F., 660, 961, 1082 

Piroth M. D., 246 

Pirraco R., 1194, 1201 

Piscopo A., 881 

Pitkänen M., 357 

Pittomvils G., 222, 1152 

Pitz C., 116, 243, 893 

Piñeiro M., 580 

Pla L., 1120 

Plataniotis G., 1337 

Plekhanov V., 1438 

Poettgen C., 499 

Pohl F., 1153, 1351 

Pointreau Y., 1540 

Poitevin Chacon A., 768 

Pol van de M., 872 

Polanska J., 487, 1436, 1437 

Polanski A., 447, 487, 1436, 1437 

Polednik M., 94 

Polgár C., 42, 834, 1395 

S 509 

Polivka M., 1440 

Polkowski W., 718 

Polli C., 912 

Polo Rubio J. A., 198 

Polsinelli M., 276 

Pompeo E., 890 

Pompucci A., 674 

Pontes M., 349, 1532 

Pontes M. S. B., 1155 

Pontvert D., 1440 

Pool R., 1142 

Poole B., 62 

Poon E., 1276, 1279, 1302 

Poortmans P., 315, 356, 384, 919, 1548 

Popescu I., 1278, 1286 

Popiela T., 718 

Popov I., 716, 717 

Popov S., 595, 1408 

Porcher R., 943 

Porras M., 1013 

Porto Vazquez C., 612, 700 

Pos F., 453, 1116, 1181 

Posch A., 1361 

Possanzini M., 690, 692 

Post W., 967 

Postgård P., 1473 

Postma E., 245, 269 

Pouli A., 928 

Poulin Hansen M., 308 

Poulsen P. R., 477, 1404 

Poupon E., 1231 

Pourghiasian M., 66 

Powe J., 861 

Powell J., 187 

Powell S. N., 47 

Poynter A., 317, 804 

Praag J., 242, 902, 1011 

Prabhakar R., 417 

Pradat P. F., 943 

Pradell J., 708 

Praestegaard L., 1208 

Pramana J., 428 

Pranger M., 218 

Pras E., 770 

Prasad R., 800 

Preusser M., 664 

Prevost B., 425 

Prezado Alonso Y., 346 

Price A., 864 

Price P., 1498 

Primavera A., 592, 611 

Principi M., 656 

Princivalli M., 1188 

Prise V., 471 

Pruim J., 992, 1096 

Pruschy M., 161 

Przeorek W., 274 

Præstegaard L., 1404 

Prévost J. B., 50, 902 

Pucciarelli S., 715 

Pudelko M., 625, 631 

Puertas E., 672, 708 

Pueyo G., 1426 

Pujades M., 1198, 1250, 1341, 1396 

Pujades M. C., 565, 1282, 1393 

Pujades M. D. C., 1283 

Punt K., 271 

Punt L., 401 

Purdie T., 910 

Purdy J., 62 

Purina D., 595, 1408 

Putter H., 63 

Pysklak S., 638 

Pytigorskaya V., 623 

Pérez M. A., 626 

Pöll J., 50 

Pöstlberger S., 316 

Pötter R., 55, 121, 123, 191, 280, 283, 664, 

739 

Qamhiyeh S., 297, 900 

Qiao X., 509 

Quera J., 613, 868, 1105, 1275 

Quera Jordana J., 1551 

Quick D., 933 

Quiet C., 320 

Quint S., 547, 1143, 1172


Quispe I., 708 

Qvarnström F., 291, 1505, 1507 

Qvarnström O. F., 1503 

Raabe A., 434 

Raaijmakers A., 132, 133 

Raaijmakers E., 872 

Raaijmakers N., 279, 843, 854 

Raaymakers B., 132, 331, 1110 

Rabuka C., 787 

Raby B., 871 

Racadot S., 958 

Raczek-Zwierzycka K., 573 

Rades D., 150 

Radford D. A., 995 

Radhakrishna G., 675, 896 

RadioTherapy Technologists Section E. R. O. 

G., 445 

Radola D., 1537 

Radosevic-Jelic L., 716, 717 

Rago L., 1323 

Ragona R., 1016, 1166, 1452 

Rahim H., 644 

Rahimi A., 1200 

Rahman F., 803, 804 

Rajan V., 96 

Rakovitch E., 152, 629 

Ramalho M., 349 

Ramella S., 592, 611, 890 

Ramer C., 1375 

Ramer R., 1232 

Ramirez M. L., 358 

Ramos J., 708 

Ramos M., 255, 582, 646, 672, 708, 795, 1184 

Ran W., 704 

Rancati T., 454, 1004, 1042 

Rancea A., 1494 

Randazzo N., 338 

Rangaswamy G., 657, 878, 1109 

Rao B., 245, 269, 437, 876, 1517 

Rao N., 788 

Raoust I., 606 

Rasch C., 85, 241, 275, 297, 304, 428, 514, 

518, 522, 900, 1150, 1170, 1522 

Rasmussen P. C., 702 

Rassiah-Szegedi P., 1136, 1297 

Rath G., 741 

Rath G. K., 766 

Rathee S., 1154 

Ratib O., 636 

Rauth S., 1491, 1496 

Ravasco P., 659 

Ravasio A., 640 

Rawlings C., 64, 317, 936 

Razek A., 1021 

Reberg K., 554 

Reckwerdt P., 62 

Reddy V. A. P., 1196 

Redpath A., 232, 1182 

Reggioli V., 338 

Rehbinder H., 101, 1014, 1327 

Reig A., 613, 868, 947, 964, 1275, 1509 

Reig Castillejo A. M., 1105, 1551 

Reiman A., 899 

Reimoser S., 337, 987 

Reitkopf S., 1501 

Reizenstein J., 361 

Rembak-Szynkiewicz J., 1489 

Remeijer P., 475, 1116, 1150, 1181, 1397 

Remmelzwaal J., 271 

Renard L., 56 

Reni M., 244 

Renier M., 346 

Reniers B., 229, 1147, 1276, 1279 

Renschler T., 1021 

Repa I., 571, 906, 1123 

Reyes Lopez V. M., 582 

Reynaert N., 222 

Reynard E., 1126 

Reynders T., 135, 525 

Reyners A., 967 

Reynolds J., 1434 

Rezende K., 648 

Rhodes M., 62 

Rhys-Evans P., 792 

Ribas M., 1196 

Ribeiro F., 1552 

Ricardi U., 918, 1016, 1166, 1452 

Riccardi S., 29 

Richard Holm A., 929, 1078 

Richardson C., 1289 

Richart J., 565, 1341, 1393 

Richart Sancho J., 1198 

Richetti A., 585 

Richetto V., 667, 763, 953, 1386 

Richter A., 491 

Richter C., 1178 

Richter P., 718 

Richter V., 1073 

Ried T., 1478 

Riem H., 1399, 1405 

Riepl M., 1153, 1351 

Rietveld D., 278 

Rigash J., 86 

Righetto R., 1253 

Rijken P., 469 

Rijkhorst E., 72 

Rijkhorst E. J., 233 

Riley S., 1217, 1222 

Rimmer Y., 305, 1077, 1167, 1183 

Rinaldi C. G., 833 

Ringash J., 785 

Rio E., 1018, 1482 

Rios P., 676 

Rit S., 473 

Ritter M., 93 

Ritter S., 1481 

Rivard M., 125, 1250, 1282, 1283 

Rivera M., 1062 

Rivera S., 1540 

Roa W. H. Y., 899 

Roberg K., 260, 1484, 1493 

Robert M., 830 

Roberto E., 1386 

Roberto K., 177 

Roberts D., 655 

Rocco B., 1028, 1039, 1051, 1054 

Rochet N., 745 

Rock L., 1547 

Rodemann H. P., 70, 1427 

Rodrigues R., 217 

Rodriguez de Dios N., 1105, 1551 

Rodriguez Garcia A., 1190, 1338, 1340 

Rodriguez Garcia A. B., 1120 

Rodriguez I., 1129 

Rodriguez M., 358 

Rodriguez N., 613, 947, 1275, 1509 

Rodriguez Perez A., 771, 869, 959 

Rodriguez S., 1198, 1336, 1393 

Rodriguez Villalba S., 565 

Rodríguez N., 868, 964 

Rodríguez Ponce M., 768 

Roegiers A., 686 

Roeloffzen E., 311, 989 

Roelofs E., 1207 

Roels S., 9, 212, 249, 312, 1327 

Roepman P., 524 

Roesink J., 279, 740, 843, 854 

Rogers L., 637 

Rogers S., 64, 936 

Rojas J. M., 972 

Roland T., 1136 

Roldão M., 1552 

Rolfo A., 1048, 1079, 1134 

Rolfo M., 589, 1134, 1514, 1533 

Rolland F., 794, 798 

Romagnoli R., 840, 882 

Romano O., 691 

Romdhani Messai T., 757 

Romero P., 811 

Romick B., 1021 

Rondi E., 1039, 1051 

Rondi N., 1166 

Roos D., 966 

Roos M., 1524 

Roques T., 791, 818, 826 

Rorke S., 862 

Rosario T., 334 

Rosenfelder N., 1112 

Rosengren B., 1075 

Rosenthal D., 1170 

Rosenwald J. C., 1238 

Rosewall T., 1412 

Rosier J. F., 972 

Ross G., 1112 

Rosser K., 83 

Rossi C., 715 

Rossi E., 969 

Rossi M., 392 

Rossi R., 656, 669, 970, 971 

Rostkowska J., 939, 1226, 1258, 1260, 1261 

Roszak A., 746, 769, 1553 

Roth A. D., 682 

Roth S., 621 

Rothkamm K., 71 

Rottenfusser A., 664 

Rouschop K., 390, 470, 472 

Roussos J., 86 

Routledge J., 1441 

Routsis D., 305, 317, 531, 1183 

Rovirosa A., 580, 747 

Rowbottom C., 815, 1463 

Roxby K., 1210 

Ruaud J. B., 372 

Rubello D., 269 

Rudat V., 150 

Rudnik A., 658 

Rudolfsson C., 1516 

Ruggieri R., 397 

Ruiz M. J., 1129 

Rusanen M., 1399, 1405 

Rusin M., 1433 

Russ-Gal P., 1101 

Russell N., 289 

Russell S., 305, 864, 1167 

Russo I., 793 

Rutkowska E., 89, 1179 

Rutkowski T., 274, 836, 1437 

Rutqvist L. E., 842 

Rutten H., 271 

Rutz H. P., 292, 949 

Ruzickova J., 764 

Ryberg M., 451, 991, 1078 

Rychter A., 677, 749 

Rykers K., 589 

Ryott M., 810 

Ryu M. H., 707 

Rzepecki J., 361 

Rödel C., 1471 

Röper B., 468, 1431 

Rødal J., 1175 

Saarilahti K., 1443 

Sabado C., 255 

Sabater Martí S., 1062 

Sabater S., 747 

Sabbas A., 797, 1034 

Sacco C., 1119 

Sadikov E., 616 

Sadrozinski H., 338 

Saha S., 570, 609 

Sahih A., 374 

Sahin B., 1204 

Sakai M., 750 

Sakayauchi T., 720, 911, 1031 

Sakellaropoulos G., 1446 

Salamon E., 315, 1102 

Saleem A., 11 

Saleh H., 1354 

Salgado L., 1201 

Salgado M., 1370 

Salinas J., 1013 

Salmaggi A., 1430 

Salminen E., 355 

Salvador Garrido N., 612 

Salvajoli J. V., 566, 808 

Salvat F., 373 

Salvi F., 840, 882 

Salzwimmer M., 460 

Samm B., 1021 

Sampayan S., 62 

Samper Ots P. M., 771, 869, 959 

Sanchez de Toledo J., 255 

Sanchez-Reyes A., 799, 1061, 1120, 1190, 

1245, 1340 

Sanchez-Reyes Fernandez A., 1338 

Sandberg K., 993, 994 

Sanders D., 62 

Sanders I., 703 

Sandilos P., 934, 1114 

Sandison G., 339

AUTHOR INDEX 

Sandle S., 1373 

Sandler H., 114 

Sandra H., 119 

Sanghera B., 1439 

Sanguineti G., 788, 832 

Sankreacha R., 629 

Santacaterina A., 970, 971 

Santamaria Torruco B., 768 

Santangelo V., 1253, 1291 

Santoro L., 1051, 1054 

Santos M., 349, 565, 1198, 1393 

Santos O., 1552 

Santos V., 349, 1532 

Santvoort van J., 407 

Sanz J., 947 

Sanz Latiesas X., 1105, 1551 

Sanz M., 1128 

Sanz X., 613, 868, 964, 1275, 1509 

Sapru W., 1527 

Saracino B. M., 248, 1029, 1056 

Saran F., 379, 380, 516 

Saraydaroglu O., 823 

Sardo A., 667, 763, 953, 1386 

Saricaoglu H., 927 

Sarihan S., 641, 661, 927 

Sarin R., 1422 

Sarkar S., 570 

Sarkar V., 977, 1375 

Sarkis R., 725 

Sarper B., 767 

Sarrazin T., 845 

Sarrut D., 1209 

Sasaki R., 827 

Sasaki S., 921 

Sasaki T., 591, 1083 

Sasiadek W., 1547 

Sasso G., 1059 

Sastre Padró M., 1175 

Satchwill K., 575, 1068 

Sato H., 844 

Sattler G. A., 652 

Sauer O., 491 

Saunders M., 471, 1439 

Savelkouls K., 390, 470 

Savov A., 1459 

Sawada S., 1490 

Sawant A., 78, 141, 875 

Saxner M., 1272 

Scalchi P., 908, 998, 1253, 1291 

Scalliet P., 2 

Scalone S., 422 

Scambia G., 236 

Scarabeo F., 236 

Scarbrough T., 1170 

Scardino E., 1028, 1039, 1051, 1054 

Scarleas C., 1114 

Schaefer J., 1053 

Schaeken B., 581, 1191 

Schellhorn E. R., 554 

Schiff B., 850 

Schiff P., 618 

Schiffner D., 333 

Schild S., 150 

Schill S., 883 

Schilstra C., 247 

Schilstra K., 218, 240 

Schinagl D., 455 

Schipani S., 880 

Schippers J., 258, 287 

Schippers J. M., 1453 

Schippers M., 203 

Schlegel W., 297 

Schlief A., 622 

Schmid T., 1431 

Schmidt M., 286, 563, 574, 1118, 1501 

Schmidt R., 62, 345, 1223 

Schmitz P., 816 

Schmoll H., 410 

Schneeberger P., 215 

Schneeweiss A., 745 

Schneider C., 453 

Schneider T., 1512 

Schneider U., 534 

Schoenmaker E., 1020 

Schomberg P., 1093 

Schornagel J., 275 

Schouten - Meeteren A., 254 

Schramm O., 938 

Schratzenstaller U., 883 

Schrauwen B., 1252 

Schreuder H., 756 

Schrijvers D., 802 

Schröder F. H., 999 

Schubert K., 262, 263, 745 

Schulte R., 338 

Schultheiss T., 333 

Schultz H., 1404 

Schulz-Ertner D., 1092, 1481 

Schuuring E., 428 

Schwaiger M., 95 

Schwarz M., 296 

Schwarz R., 1093 

Schwierczok B., 1100 

Schöller H., 892 

Schönborn T., 1223 

Schüssler S., 739 

Schütze C., 128, 314 

Scoccianti S., 965 

Scoffings D., 633 

Scollen S., 432 

Scorsetti M., 728 

Scott A., 107 

Scott M. C., 1072 

Scott N., 385 

Scott W., 687 

Scotti V., 639 

Scrase C. D., 803, 804 

Scremin E., 998 

Sculier J. P., 425 

Scurr E., 1118 

Scvortsova O., 903 

Se Hoon P., 885 

Sebag-Montefiore D., 164, 675, 723, 1104 

Sebastian E., 324 

Sebestyén Z., 1216, 1329 

Sederholm C., 523 

Sedlaczek P., 631 

Sedlmayer F., 244, 644, 892 

See A., 1048 

Seewald D. H., 316 

Segedin B., 572 

Seidel C., 1478 

Seiersen K., 1404 

Seigneuric R., 437 

Selbach H. J., 1512 

Selek U., 901, 937, 1458 

Sen M., 800, 856 

Senan S., 114, 139, 213, 1141 

Senkus-Konefka E., 382 

Senthamizhchelvan S., 636 

Sentinelli S., 248 

Seo Y., 729, 730, 751, 986 

Seong J., 714, 772, 805, 1335 

Seppenwoolde Y., 1556 

Seppi T., 1361 

Serafini F., 1028, 1054 

Sergieva K., 1236 

Sernbo G., 1189 

Serviss D., 575, 1068 

Servitja S., 747 

Setti M., 1406 

Seung Jae H., 1449 

Seung Woon P., 1449 

Severens J., 337, 987 

Sevillano M. D. M., 1062 

Shaffer R., 1357 

Shah M., 774, 821 

Shah P. R., 941 

Shah S. M., 1021 

Shah V., 941 

Shahriari M., 1135, 1265 

Shakeshaft J., 1222 

Shakespeare D., 1026 

Shakhova N., 1438 

Shankar V., 941 

Sharma D., 741, 766 

Sharma P., 561 

Sharp L., 34, 1542 

Shcherbinin S., 861 

Sheehan B., 773 

Sheehan F., 861 

Sheibani K., 1388 

Sheng X., 1230, 1242 

Sherman I., 862 

S 511 

Shi C., 342, 888, 1133, 1168, 1195, 1375, 

1403, 1469 

Shibamoto Y., 663, 921 

Shikama N., 761 

Shilkrut M., 954 

Shim S., 1124, 1228 

Shim S. J., 734 

Shimatani Y., 694 

Shimbo T., 671, 1024 

Shin D., 1221 

Shin H. Y., 653 

Shinbo M., 1108 

Shiraishi K., 990, 1322 

Shishido F., 844 

Shoda J., 710 

Short S., 1500 

Shrivastava S. K., 561, 724, 742, 744, 1422 

Shuin T., 997 

Shumadine J., 1354 

Siami P., 1021 

Sibata C., 905 

Siciliano R., 660, 961, 1082 

Siebert F. A., 122, 1387 

Siegemund A., 286 

Siegrist C., 148, 215 

Signor M., 1119 

Sigon R., 715 

Sigurdardottir S., 291, 1503 

Sijtsema M., 1371 

Sikora M., 484 

Silipigni S., 819 

Siljamäki S., 1399, 1405 

Silvano G., 426 

Sim S. J., 907 

Simcock R., 189 

Simmons N., 655 

Simo R., 776 

Simon L., 1238 

Simonova G., 974 

Simons J., 116, 243, 893 

Simonsson M., 291, 1503, 1505, 1507 

Simpson J., 1059 

Simão C., 1552 

Singh A., 281 

Sioletic S., 1492 

Sioni A., 928 

Sipala V., 338 

Sire C., 360 

Sirois S., 348 

Sjodin H., 557 

Sjodin K., 1542 

Sjöberg C., 887 

Sjödin H., 361 

Sjögren R., 894 

Sjöström D., 299, 1205, 1219 

Skarlatos J., 963 

Skladowski K., 274, 427, 1087, 1437 

Skorpen T., 73 

Skowronek J., 596, 824, 1017, 1063 

Skrobala A., 1314 

Skrocki E., 722 

Skrzypski M., 524 

Skworcow P., 374 

Slade A., 127 

Slagmolen P., 9, 249, 309, 312 

Slampa P., 764 

Slevin N., 815, 1441 

Slootweg P., 310 

Slosarek K., 274, 1346, 1528 

Slosberga I., 595, 1408 

Slot A., 63 

Slotman B., 139, 213, 277, 278, 356, 550, 

1141 

Sluiter W., 652 

Small C., 657, 960, 1109 

Smaniotto D., 645, 706 

Smee R., 668 

Smeele L., 289 

Smid J., 1122 

Smid L., 852 

Smit E., 524 

Smit V., 63 

Smith C., 862 

Smith F., 1434 

Smith G., 127 

Smith J., 325 

Smith M., 982, 1009


Smith P., 826 

Smith R., 783, 850 

Smith S., 804, 984, 1463 

Smits B., 1367 

Smitsmans M., 478 

Smolska B., 567 

Smolska-Ciszewska B., 568 

Smrdel U., 1184 

Smylie M., 899 

Snee M., 864, 896 

Snider H., 320 

Snyers A., 814 

So Young J., 583 

Sobhani M., 1388 

Sobotta B., 362 

Soehn M., 293 

Soete G., 111, 988 

Sohn C., 745 

Sokó M., 1344 

Solberg T., 377 

Solca F., 128 

Soldà F., 881, 979 

Soler M., 1550 

Soler Tortosa M., 891, 1065 

Solin L., 234 

Somaiah N., 71 

Sommer S., 1481 

Somoano F., 358 

Somogyi A., 1076 

Son J. W., 907 

Son Y. I., 828 

Sondergaard J., 332 

Song C. H., 859 

Song S., 1354 

Song W., 830 

Song Y., 681 

Songur N., 874 

Sonke J. J., 72, 76, 221, 233, 241, 304, 

330, 392, 414, 466, 473, 475, 

478, 481, 514, 909, 1150, 1170, 

1522, 1523 

Soo-Jin P., 885 

Sopylo R., 718 

Sorcini B., 1132, 1146, 1160, 1162 

Sorensen A., 1021 

Sotiropoulou A., 928 

Sotnikov V., 903 

Sotoca Ruiz A., 771 

Soubasi E., 956 

Souda J., 721 

Soukalova H., 764 

Soukup M., 293 

Souto C., 349 

Souvatzoglou M., 468 

Spagnolli F., 840, 882 

Specht L., 230, 597, 1301 

Speleers B., 543, 1036 

Sperduti I., 853, 1029 

Spiegl K. J., 316 

Spina M., 422 

Spire W., 655 

Spoelstra F., 213 

Sprangers A., 727 

Sprawka A., 722, 897 

Spry N., 452 

Spych M., 677, 749, 913 

Sriram K., 437 

Sroka-Perez G., 262, 938 

Stacey C., 579 

Stachlewski R., 769 

Stadelmann O., 340 

Stafford E., 832 

Stagnitto D., 592, 611 

Stalpers L., 150 

Stamatelou M., 928 

Staniaszek J., 940 

Stankovic V., 717 

Stanley S., 540 

Stapleton A., 760 

Starmans M., 430, 437 

Stasi M., 454, 1004, 1042, 1244 

Staszek U., 625, 631 

Stathakis S., 977, 1009, 1040, 1074, 1133, 

1168, 1174, 1297, 1375, 1418 

Stecco A., 1117 

Steenbakkers R., 522 

Stefanitsi P., 928 

Steffen Greilich S., 1380 

Steggerda M., 326 

Steigler A., 452 

Steil V., 94, 1401 

Steineck G., 235, 282, 307, 762, 1130, 1444, 

1448 

Steins M., 884 

Stellingwerf P., 1345 

Stellingwerff G., 1122 

Stenberg A. M., 1542 

Stenfert Kroese M., 63 

Stephenie R., 978 

Stergiou C., 934 

Sterpin E., 143, 1296 

Sterzing F., 745, 884 

Steven G., 327 

Stevens L., 1069 

Stewart D., 877 

Stewart F., 289, 1088 

Stewart J., 101 

Stewart R., 1079, 1514 

Steyn T., 1113, 1529 

Stieler F., 94, 1401 

Stierner U., 654, 1428 

Stiggelbout A., 962 

Stillie A., 608 

Stimato G., 592, 611 

Stobiecki M., 1436, 1437 

Stock M., 55 

Stojanovic S., 716 

Stoker J., 1052 

Stokman M., 1455 

Stoll A., 1115 

Storch K., 68 

Storm H., 494 

Storme G., 135, 525, 711, 988 

Stout R., 1138 

Strackee S., 779 

Strand S. E., 207 

Stratakis J., 917, 952 

Streichert T., 1432 

Streltsova O., 755 

Strengell S., 1411 

Strigari L., 248, 853, 988, 1029, 1056 

Strnad V., 160 

Strojan P., 852 

Strojek J., 1087 

Strojnik A., 1416 

Stroobants S., 9, 309, 312, 1326 

Stroom J., 221, 350, 622 

Struikmans H., 315, 407 

Stryczynska G., 718 

Strååt S., 77, 1400 

Studnicka M., 892 

Studynkova A., 932 

Stuessi A., 1420 

Stuschke M., 499 

Stürzbecher H. W., 1432 

Su F. C., 1040, 1168, 1469 

Subramanian V., 809 

Suchowerska N., 1197, 1467, 1474 

Suefuji H., 619, 925 

Sugahara S., 710, 721 

Sugane T., 863 

Sugie C., 921 

Sugimura K., 827 

Suh C. O., 643, 714, 805 

Suh T. S., 1234 

Suh Y. G., 643 

Suleiman M., 1248 

Sullivan J., 62 

Sultanem K., 1126 

Sultanov B., 1459 

Sulyok Z., 680 

Sumida I., 1158 

Summers H., 540 

Sun A., 910 

Sun Hee K., 607 

Sundberg A., 235 

Sundfør K., 554 

Sundqvist E., 554, 1424 

Sung Whan J., 885 

Supiot S., 1018, 1482 

Surenkok S., 922 

Surucu S., 1458 

Sutton D., 946 

Sutton P., 1511 

Suwinski R., 274, 427, 731, 836 

Suzuki G., 619, 925 

Suárez J. F., 328 

Svatos M., 78, 141 

Svensson R., 226 

Swanson G., 449, 977, 1009, 1040, 1057, 

1074, 1168, 1375 

Swift S., 1104 

Swiggers P., 1002 

Swindell R., 1000 

Swinnen A., 1193, 1233, 1303, 1326 

Swinscoe J., 916, 1165 

Swärd J., 559 

Sykes A., 815, 1441 

Sykes J., 136, 519, 540, 1104, 1157 

Syljuasen R., 4 

Symon Z., 623, 1304 

Syrén H., 1071, 1075 

Szczepanik K., 1538 

Szczurek L., 1314 

Szegedi M., 1136 

Szewczyk K., 625, 631 

Szigeti A., 1216, 1329 

Szlag M., 567, 568 

Szpakowska M., 699 

Szymanowski H., 205 

Szynglarewicz B., 625 

Sánchez-Reyes A., 580 

Söhn M., 298, 300, 362, 1015 

Sörensen J., 436, 1001 

Søndergaard J., 1182 

Sørensen P., 895 

Sørensen T., 1180 

Tabak H., 1534 

Tabata K., 647, 648, 670 

Tabernero J., 708 

Tadokoro M., 591, 1125 

Tagliaferri L., 674, 1070, 1081 

Tahara S., 1161 

Taheri-Kadkhoda Z., 649, 801, 1428 

Tai T. H. P., 616 

Tait D., 272, 719, 733, 1112, 1139, 1421, 1462 

Tajer J., 939 

Takacs I., 1020 

Takacsi-Nagy L., 834 

Takahashi M., 671, 1024 

Takahashi T., 1108 

Takai Y., 911, 1031 

Takeda K., 720, 911, 1031 

Takemoto M., 1161 

Takes R., 428, 814 

Tal M., 574 

Talamonti C., 338 

Talbot J. N., 1440 

Tamaki T., 435 

Tambone C., 998 

Tamer L., 1477 

Tan L., 945 

Tanaka K., 1127 

Tanck E., 975 

Tanderup K., 173, 303, 480, 537, 702, 1180, 

1254 

Tangen C., 449, 1057 

Tao Y., 126 

Tararova E., 755 

Tarella C., 918 

Tarnavski N., 1292 

Tarnawski R., 252, 274, 658, 1436 

Tarte S., 866 

Tasca A., 998 

Tasdelen I., 614 

Taussky D., 229, 1047, 1159 

Tayama Y., 920 

Taylor C., 1000 

Taylor H., 379, 380, 516 

Taylor I., 408 

Teguh D., 816 

Tei T., 702 

Teissier E., 606 

Teixeira G., 566 

Teixeira N., 349, 1155 

Teke T., 1278 

Temurhan M., 909 

Ten Haken R., 100, 279, 474, 637 

Tenekeci N., 873 

Tenhunen M., 357, 1339, 1411, 1443

AUTHOR INDEX 

Teofili L., 674 

Tepetam H., 1095 

Terhaard C., 279, 354, 843, 854 

Tersteeg R., 560 

Teshima T., 761, 1083 

Tesselaar M., 271 

Testolin A., 908, 998 

Tewatia D., 416 

Thames H., 314, 316, 431, 467 

Tharavichitkul E., 1058 

Thariat J., 1309 

Thawani N., 759 

Theberge V., 630 

Theelen A., 665 

Theodoros P., 968 

Theodorou K., 1248, 1293, 1359, 1445 

Thiam C. O., 1267 

Thierens H., 222 

Thillays F., 1363 

Thirion P., 87, 539, 657, 829, 878, 960, 1045, 

1109, 1511, 1521, 1547 

Thissen B., 1010 

Thom E., 1223 

Thomas G., 168, 192 

Thomas M., 884 

Thomas S., 305, 1077 

Thompson A., 787, 861 

Thompson I., 449, 1057 

Thompson R., 1271, 1310 

Thomsen M. S., 599 

Thornberg C., 601, 1334 

Thorstad W., 464 

Thukral A., 735 

Thunberg U., 1488, 1505 

Thursfield V., 1044 

Thurzo L., 584 

Thurzó L., 1101 

Thwaites D., 108, 136, 1104, 1157, 1271, 

1310, 1324 

Tian S., 704 

Tielenburg R., 350 

Tilikidis A., 835, 1146, 1446 

Tillikainen L., 1284, 1399, 1405 

Tilly N., 224, 1381 

Timke C., 884, 1092 

Timmerman R., 1186 

Timmermann B., 292, 294, 949 

Ting J., 1170 

Tiszlavicz L., 693 

Todisco L., 918 

Todor N., 1494 

Todorovic M., 1223, 1237 

Toet-Bosma M., 756 

Tohme C., 725 

Tohno E., 710 

Tohyama N., 750 

Toita T., 761 

Tokatli F., 588, 922 

Toker A., 1204 

Toklowicz K., 1537 

Tokmakidis S., 1475 

Tokuuye K., 710, 721 

Tolento G., 1121 

Tolunay S., 641, 661 

Toma-Dasu I., 1272, 1316, 1327 

Tombolini V., 881, 979 

Tome W., 416 

Tomio L., 276, 1369 

Tomita N., 663 

Tomsej M., 448 

Tomé W., 396 

Tonetto V., 1188 

Tongaonkar H., 744 

Topal B., 526 

Topolnjak R., 1150 

Tore G., 767 

Tormo A., 1393 

Torrens M., 934 

Torsti T., 1284, 1399 

Tortoreto F., 590, 1111 

Toshima M., 844 

Touboul E., 1257 

Toulany M., 70 

Tournel K., 135, 525, 711 

Toy Inal A., 1410 

Tozer G., 471 

Traberg A., 523, 1404 

Track C., 316 

Traila A., 1494 

Tramm T., 458 

Trampal C., 1120 

Traneus E., 224, 1266, 1319, 1381 

Trebicky F., 685 

Treeby J., 1183 

Trela K., 567, 568, 617, 789 

Tremlett J., 64, 936 

Trichter S., 1034 

Trigo L., 1201 

Trindade M., 1249, 1300 

Trippa F., 426, 656, 662, 669, 965, 970, 971 

Trivedi H. L., 941 

Trnkova P., 123, 283 

Trodella L., 592, 611, 890 

Troost E., 310 

Trott K. R., 533 

Trovik C., 1089 

Truccolo I., 422 

Tsakanikas S., 928 

Tsang E., 1286 

Tsang Y., 109, 1330 

Tsiamas P., 1293 

Tsiarkatzi M., 841 

Tsien C., 637 

Tsilika E., 973 

Tsougos I., 1248, 1445 

Tsoutsou P., 841, 1475 

Tsuboi K., 710, 721 

Tsuji C., 619, 925 

Tsujii H., 297, 743, 863 

Tsujitani M., 129 

Tsuzuki A., 591 

Tsuzuki K., 591, 1125 

Tsvang L., 1304 

Tuan J. K. L., 719 

Tudor S., 1167 

Tufano R., 832 

Tukiendorf A., 731 

Tummers P., 237 

Tuna S., 786 

Tuncel N., 578 

Tung Z., 484 

Turchin I., 1438 

Turcsányi V., 1101 

Ture M., 588 

Turesson I., 201, 291, 436, 556, 654, 1001, 

1012, 1060, 1392, 1425, 1488, 

1503, 1505, 1507 

Turner S., 452 

Tveit K. M., 273 

Twickler M., 814 

Twohig K., 87 

Twyman N., 317, 1330 

Tyc-Szczepaniak D., 696, 722 

Tynan P., 1418 

Tynan T., 1074, 1232 

Tzedakis A., 917, 952 

Tzikas A., 1328 

Tägtmeyer L., 1512 

Tímár J., 1476 

Ubbels F., 218, 1122, 1345 

Ue H., 591, 1125 

Uematsu M., 978 

Uesugi Y., 671, 1024 

Uhrdin J., 1327, 1332 

Uitterhoeve L., 354 

Ullén A., 559, 991, 993, 994, 1187 

Ulrich S., 138 

Umesh M., 742 

Uner A., 1458 

Unkelbach J., 301 

Uno H., 1161 

Unsal D., 1457 

Uozumi J., 925 

Ural D., 709, 858 

Urbanczyk H., 695, 983, 1100, 1112, 1528, 

1538 

Urdambidelus A., 795 

Urgesi A., 667, 763, 953, 1386 

Ursino S., 683, 1163, 1362 

Urso G., 728 

Ustun H., 1425 

Usubutun A., 1458 

Utehina O., 595, 1408 

Uttman K., 838 

Uusijärvi H., 1270 

Uzal C., 588 

Uzcanga M., 811 

S 513 

v.d.Linden Y., 354 

Vaalavirta L., 1411 

Vaandering A., 56 

Vainikka L., 260 

Vakaet L., 222 

Valcarcel F., 879 

Valdagni R., 418, 454, 1004, 1042 

Valdes M., 255 

Valdman A., 559, 991 

Valente S., 889 

Valentine H., 1498 

Valentini C., 268 

Valentini V., 236, 244, 245, 249, 268, 352, 500, 

632, 706, 712, 715, 777, 819, 

833, 889, 930, 969, 1185, 1358, 

1506 

Vallis K. A., 61 

Vallyon M., 906 

Vamvakas E., 624 

van ’t Veld A., 247, 1173, 1214, 1342, 1345, 

1348, 1371, 1419 

van Aken J., 975 

van Baardwijk A., 306, 463 

Van Beek A., 652 

Van Beek K., 876 

van Beek S., 241, 1522 

Van Brussel S., 727 

van Bunningen B., 63 

van Coevorden F., 1088 

Van Cutsem E., 502 

van Dalen J., 310, 455, 1098 

van de Bunt L., 756, 1110 

Van de Burgt M., 350 

van de Kamer J., 1052, 1169, 1181 

van de Kar M., 779 

van de Pol M., 119, 919, 1367, 1368, 1407, 

1548 

van de Vaart P., 1113, 1529 

van de Velde C., 501, 962 

van de Velde T., 524 

Van De Vondel I., 135 

van de Water T., 240, 297 

Van de Wiele M., 1536 

van den Berg C., 124, 133, 311, 740 

Van den Berg G., 652 

van den Berg N., 854, 989, 1103 

Van den Bergen B., 133 

Van den Bergh A., 652 

van den Bergh F., 247, 992 

van den Beucken T., 390, 470, 472 

van den Bogaard J., 306 

Van den Bogaert W., 219, 315 

van den Bosch M. R., 124 

van den Brekel M., 241, 428 

Van den Broecke R., 237 

van den Broek L., 66, 428 

Van den Heuvel F., 219, 1193, 1233, 1303, 

1349, 1398, 1402 

van den Hoff J., 1479 

van den Tol P., 63 

Van den Weyngaert D., 802, 1002, 1191, 1536 

van der Baan P., 344 

van der Borden A., 1342, 1345, 1348 

van der Grient H., 779, 1390 

van der Heide U., 74, 311, 331, 740, 756, 989, 

1023, 1103, 1171 

van der Hulst P., 1214, 1342, 1345 

van der Kogel A., 131, 310, 390, 469 

van der Laan B., 428 

van der Laan H. P., 144, 147, 218, 247, 1122, 

1371 

van der Leije B., 1556 

van der Linden Y., 967, 975, 1534 

van der Poel H., 326 

van der Put R., 132, 331, 1110 

van der Sijp J., 1212 

van der Steen-Banasik E., 63 

van der Tol P., 1407 

van der Voort van Zijp N., 242 

van der Voort van Zyp N., 902 

van der Wee R., 1371 

van der Wielen G., 476


van der Zee C., 285, 732, 1311 

van der Zee J., 758 

Van Dijk I., 132 

van Dijk M., 1096 

van Dijk-Peters F., 1371 

van Dongen G., 256 

van Egmond J., 1164, 1212, 1529 

van Eijkeren M., 237 

van Elmpt W., 479, 482, 944, 1137 

van Erk A., 437 

Van Esch A., 1102, 1284, 1399, 1405 

van Gelder I., 1345 

Van Gestel D., 802, 1191 

van Gils C., 1023 

van Gils F., 488, 1046 

van Goethem M. J., 1376 

Van Greveling A., 543 

van Helvoirt R. P., 151 

van Herk M., 72, 91, 221, 233, 241, 257, 330, 

350, 392, 453, 466, 473, 475, 

478, 481, 496, 514, 522, 1052, 

1116, 1181, 1227, 1522 

van Herten Y., 1390 

Van Heumen M., 1519 

Van Houtte P., 425, 1251 

van Hulzen A., 1214 

van Klaveren R., 242 

van Kollenburg P., 544 

van Komen S., 1368 

van Kranen S. R., 76, 241, 466, 514 

van Kroonenburgh M., 253 

Van Laere S., 727 

Van Laethem J., 528 

Van Lier A., 133 

Van Limbergen E., 497 

van Lin E., 544 

van Lindert E., 254 

Van Loon J., 243 

van Luijk P., 258, 287, 1173, 1453 

van Mastrigt G., 285, 456, 732 

Van Meerbeeck J., 876 

van Mourik A., 76, 145, 602, 1519 

Van Nieuwenhove Y., 711 

van Os M., 1143 

van Os R., 231 

Van Poppel H., 1067 

van Rhoon G., 758, 1311 

van Riel N., 437 

van Rooij P., 816 

van Rooijen D., 351, 1142, 1169 

van Santvoort J., 1164, 1320 

van Stiphout R., 245, 269 

Van Sörnsen de Koste J., 213 

van t Riet A., 1531 

van Tienhoven G., 356, 1052 

van Veen E. B., 446, 447 

van Velthuysen M. L., 428 

van Vliet C., 85, 304 

Van Vliet-Vroegindeweij C., 1519 

van Vliet-Vroegindeweij C., 76, 145, 684, 1150 

van Vliet-Vroegindewij C., 602 

van Vulpen M., 74, 124, 132, 311, 989, 1023, 

1103, 1171 

van Wieren M., 1368, 1407 

van Wieringen N., 1052, 1390 

van Wingerden J., 1212 

van Zijtveld M., 483 

Vandecasteele K., 237, 1007 

Vandecaveye V., 309, 462 

Vander Poorten V., 462 

Vanderstraeten B., 775 

Vandevelde G., 32 

Vandulek C., 571 

Vanetti de’ Palma E., 106 

Vanetti E., 79, 140, 335, 1199 

Vangipurapu S., 820 

Vanhauten B., 253, 306 

Vanikar A., 941 

Vannozzi R., 639 

Vanoni V., 1225, 1369 

Vanregemorter J., 1325 

Vanstraelen B., 239, 517, 923 

Varela Pazos A., 612, 700 

Varga B., 680 

Varga L., 693 

Varga Z., 584 

Vargas M., 580 

Vargas R., 1343 

Varveris A., 917 

Varveris C., 1294 

Varveris H., 917, 952 

Vasconcelos J., 317 

Vasev N., 628 

Vasquez Osorio E., 1172 

Vassaux G., 127 

Vassiliou V., 956, 968 

Vatanen T., 1319 

Vatnitsky S., 345 

Vautravers C., 1540 

Vavassori A., 793, 1028, 1039, 1051, 1054 

Vavassori V., 454, 1004, 1042 

Vayreda J., 1352, 1353 

Vazquez S., 1426 

Vecht C., 251 

Vees H., 636 

Vejlgaard D. L., 957 

Vela A., 81 

Velez G., 345 

Vendrely V., 270 

Veninga T., 150, 665 

Venkat R., 141, 875 

Vens C., 66 

Venselaar J., 120, 122, 1252 

Ventura M., 328 

Ventura T., 1269, 1281 

Verbakel W., 139, 1141 

Verbeek A., 1320 

Verbeek-de Kanter A., 251, 1113, 1212 

Verbeken E., 462 

Verbiene I., 1001 

Verdonck-de Leeuw I., 278 

Verdonschot N., 975 

Verellen D., 135, 518, 525, 711 

Verfaillie C., 447 

Vergeer M. R., 277 

Verhaegen F., 99, 229, 347, 1147, 1276, 1279, 

1302 

Verheij M., 297 

Verhoef C., 231 

Verma S., 610 

Vermaelen P., 256 

Vermeere W., 555 

Vermorken J. B., 802 

Verney J., 108 

Veronesi U., 1414 

Verstappen S., 455 

Verstraete J., 517, 1067, 1303, 1349 

Verweij F., 1028, 1039, 1051, 1054 

Verwey J., 1376 

Verwijs-Janssen M., 66 

Vesprini D., 1412 

Vevere I., 595, 1408 

Vicenzi L., 284, 882 

Vicini F., 320 

Vignoli L., 1163 

Vijlbrief R., 350 

Vila A., 799, 1061, 1120, 1190, 1338, 1340 

Vila T., 811 

Vilar Compte D., 768 

Vilar S., 1062 

Vilaragut J. J., 358 

Villa F., 403 

Villanueva S., 1105 

Villas M. V., 1062 

Villeirs G., 237, 543, 1007, 1035, 1036 

Vincenzo F., 1508 

Vincenzo R., 1508 

Vind Thaysen H., 702 

Vinge E., 627 

Violot D., 130, 290 

Viotto A., 1032 

Virag P., 1494 

Visser P., 1046 

Vitek P., 685 

Viterbo T., 1194, 1201 

Vitolo U., 918 

Vivek B., 820 

Viñolas N., 879 

Vlasman R., 247 

Vliegen R., 306 

Voet P., 1556 

Vogel W., 455 

Vomvas D., 956 

von Briel C., 148, 215, 318, 1144, 1420 

von Döbeln G., 557 

Voogt J., 330 

Vora N., 333 

Voroney J. P., 507, 946, 1491, 1496 

Vos P., 356 

Voulgaris S., 1030 

Vowler S., 317 

Vozenin-Brotons M. C., 130, 178, 290 

Vrieling H., 487 

Vu T., 152 

Vulpen, van M., 1003 

Vuong T., 1276 

Vynckier S., 143, 1296 

Vízkeleti J., 948 

Wada M., 589, 1134, 1514, 1533 

Wahlström O., 1089 

Wakai N., 1158 

Walaszczyk A., 1436, 1437 

Walchenbach R., 251 

Waldenström A. C., 307, 762, 1130, 1444 

Waldron J., 86, 785 

Walewska A., 1226, 1258, 1260 

Wallace M., 324 

Walsh L., 829 

Wambersie A., 535 

Wan K., 1079 

Wanders R., 115, 116, 893 

Wang J., 177, 704, 1308 

Wang L., 62 

Wang S., 681 

Wang W., 681 

Wangsa D., 810 

Wanwilairat S., 345 

Warde P., 1412 

Warenczak Z., 746 

Wareñczak Z., 699 

Warlimont B., 1010 

Warnhammar E., 1454 

Warrington A., 80, 149, 516 

Warrington J., 83 

Watson J., 62 

Wauben D., 1214 

Webb S., 51 

Weber A., 468 

Weber D., 636 

Weber D. C., 403 

Webster G., 82, 815, 1463 

Weckermann D., 36 

Weiss E., 1354 

Wells I., 976 

Weltens C., 219 

Welzel G., 1053 

Wen N., 92 

Wendling M., 221, 350, 481, 1227 

Wennberg B., 134, 523 

Wentzel-Larsen T., 513 

Wentzler D., 96 

Wenz F., 94, 1053, 1401 

Wersäll P., 929 

Wesolowska I., 731, 836, 1100, 1528 

Wessels L., 428 

West C., 375, 432, 433, 1480, 1498 

Westberg J., 137, 1099, 1355, 1374 

Westendorp R., 1531 

Wester G., 1096 

Westermark M., 1273 

Weytjens R., 727 

Whelan T., 353 

Whiley M., 460 

Whitacre E., 320 

Whitaker S., 1373 

White C., 127 

White D., 327, 603, 604, 650, 1037, 1038 

Whitehead P., 1138 

Whitworth P., 320 

Wiberg I., 142 

Wichardt G., 557 

Widder J., 114, 218 

Widesott L., 296, 1004 

Widlak P., 1437 

Widmark A., 1014, 1041 

Widak P., 1436 

Wieczorkowski L., 1178 

Wiegel T., 14 

Wiegman E., 354 

Wiersma J., 1052

AUTHOR INDEX 

Wierzbicki R., 718 

Wierzchosawska E., 699 

Wierzchowski M., 897 

Wieslander E., 1043, 1263 

Wiggenraad R., 251, 1113, 1164, 1320 

Wiggers T., 387 

Wigren A., 1542 

Wikholm G., 649 

Wilbert J., 491 

Wild J., 916, 1165 

Wilkens J., 336 

Wilkinson J., 317, 432 

Wilks R., 317 

Williams F., 1027 

Williams J., 668 

Williamson D., 238, 800, 856 

Williamson J., 1279 

Williamson K., 1543 

Willis D., 624 

Willén H., 1089 

Wilson A., 1145 

Wilson C., 432 

Wilson G. D., 1080 

Wilson J., 1439 

Wilson S., 896 

Winkler P., 106, 183 

Winston J., 1264 

Winter B., 1106 

Winter M., 1384 

Wirth M., 13 

Wishart G., 317, 432 

Withers H. R., 1465 

Witte M., 91, 257, 453 

Witteveen A., 524 

Wittgren L., 523, 598, 601, 1263, 1334, 1549 

Wiviann O., 1219 

Wlodarczyk H., 746 

Woehs V., 280 

Woerdeman L., 289 

Wojciechowska - Lampka E., 939 

Wojcieszek P., 617 

Wolanin M., 931 

Wolanska K., 1489 

Wolff D., 94, 1401 

Wolffenbuttel B., 652 

Wolny E., 678, 695, 731 

Wolstenholme V., 1112 

Wolthaus J., 392, 473 

Won Ki K., 807 

Won P., 807, 1449 

Wondrak M., 1478 

Wong F., 773 

Wong H., 634, 996 

Wong J., 333, 542, 978, 1055, 1072 

Wong P., 1126 

Wong W. L., 1439 

Wood K., 1439 

Woodhead D., 452 

Woodhouse N., 916, 1165 

Woodhouse S., 618 

Woodward B., 555 

Woodward C., 1167 

Woodward W., 23 

Working Group for Lung Cancer N., 863 

Worku M., 1500 

Worsley D., 861 

Wouters B., 256, 390, 430, 437, 470, 472, 944 

Wozniak G., 678, 836, 1365 

Wright G., 1306, 1312 

Wright P., 232, 332, 1182 

Wrona A., 1432 

Wu H. G., 831, 855, 859, 1234, 1450 

Wu J., 773, 787, 966 

Wunderink W., 231 

Wurstbauer K., 892 

Wydmanski J., 678, 731 

Wygoda A., 274, 1087, 1437 

Wylie J., 984, 1000, 1064 

Wysmans M., 1536 

Wzietek I., 567, 568 

Wárlám-Rodenhuis C., 315 

Wändel C., 423 

Wåhlin E., 1149, 1273 

Xenaki M., 917 

Xiao-Feng Sun X. F., 1495 

Xiaodong Z., 1447 

Xie J., 238 

Xie X., 101 

Xiu D., 704 

Xu G., 342 

XU W., 23 

Yahara K., 737 

Yalman D., 754, 765 

Yamada S., 720, 911, 1031 

Yamaguchi H., 1158 

Yamamoto M., 1127 

Yamamoto N., 863 

Yamanishi T., 591 

Yamano T., 1108 

Yamasaki I., 997 

Yan D., 75, 293, 298 

Yan J., 1520 

Yan X., 1276 

Yanagita H., 1108 

Yang D. S., 736 

Yang K., 729, 730, 751, 986 

Yang R., 1308 

Yao W., 1140 

Yap B., 815 

Yaparpalvi R., 759 

Yarnold J. R., 71, 317, 383, 1118, 1330 

Yaromina A., 314, 430, 431, 467, 1479 

Yartsev S., 140, 335 

Yau T. K., 837 

Yazici G., 1456 

Ye S. J., 1234 

Ye T., 594 

Yee D., 899, 1154 

Yerci O., 823, 927 

Yildirim S., 641, 661 

Yildiz D., 577 

Yildiz F., 577, 922, 1458 

Yilmaz E., 927 

Yin L., 861 

Yin Y. B., 1197 

Yip F., 345 

Yip K., 803, 804 

Yirmibesoglu E., 1457 

Ylvén J., 654 

Yoda K., 990, 1322 

Yoho M., 1514 

Yokota N., 591 

Yondem S., 1385 

Yong Chan A., 807, 1449 

Yong Ho K., 583 

Yoo H., 729, 751, 986 

Yoo S., 729, 751, 986 

Yoon H., 904 

Yoon H. I., 714, 772 

Yoon J. H., 698 

Yoon S. M., 707 

Yordanova I., 1459 

Yoshikawa K., 863 

Yoshioka T., 720 

Young K., 1145 

Young L., 877 

Yu C. S., 707 

Yu D., 594 

Yu E., 616 

Yu J., 687, 807 

Yu S., 245, 269, 876, 1517 

Yu Z., 681 

Yu-Ping C., 1546 

Yuen K., 624 

Yukawa A., 844 

Yun M., 904 

Yýldýz F., 1456 

Za T., 969 

Zabatis C., 963 

Zabel-du Bois A., 938 

Zaccariotti V., 647, 648, 670 

Zacharatou Jarlskog C., 295, 838 

Zacharias G., 726 

Zacharopoulou F., 917, 1294 

Zackrisson B., 154, 361, 1041, 1295 

Zagaynova E., 755 

Zahariev Z., 1459 

Zahmatkesh M. H., 1135, 1200 

Zaidi H., 636 

Zaidi S., 127 

Zaikova O., 1089 

Zajusz A., 567, 568, 1489 

Zaka Z., 1033 

Zakotnik B., 852 

Zalewska M., 1226, 1258, 1261 

Zandwijk N., 524 

Zannis V., 320 

Zantinge I., 1122 

Zapatero A., 37 

Zapotoczna A., 1059 

Zatari A., 877 

Zborek A., 1489 

Zefkili S., 1238 

Zehentmayr F., 469, 644 

Zenni M., 1021 

Zerini D., 1028, 1039, 1051, 1054 

Zhang P., 126 

Zhanrong G. P., 1072 

Zhao L., 339 

Zhou J., 618, 832 

Zhu T., 1268 

Zhu Y. Q., 594 

Zia A., 634 

Ziccarelli L., 660, 961, 1082 

Ziccarelli P., 660, 961, 1082 

Ziegler S., 95 

Zielinska-Dabrowska S., 1356 

Ziglio F., 1369 

Zijp M., 1545 

Zimmerman J., 78, 141 

Zimmerman R., 451 

Zimmermann F., 883 

Zinkin H., 575 

Zinkstok R., 231 

Zips D., 45, 190, 314, 430, 467, 1178 

Zoephel K., 1178 

Zografos L., 1376 

Zois C., 1475 

Zolnierek A., 625 

Zorlu F., 937 

Zotti P., 422 

Zschenker O., 1432 

Zubizarreta E., 355 

Zupan E., 589, 1533 

Zwahlen D., 238 

Zwierzchowski G., 824 

Zwijnenburg E., 354 

Zygmanski P., 90 

Zygogianni A., 781 

Ágoston P., 569 

Álvarez C., 358 

Åman P., 1089 

Åvall-Lundqvist E., 282, 810 

Ésik O., 1329 

Öllers M., 334 

Özden S., 1483 

Özkan L., 848 

Özyigit G., 1458 

Ýskit A., 1456 

S 515

Tumors Have Nowhere To Hide. 

And patients now have somewhere to turn. 

The CyberKnife® System is the ONLY commercially 

available robotic radiosurgery system that delivers 

proven sub-millimeter accuracy with unlimited reach 

anywhere in the body. 

Unprecedented Targeting Accuracy - Delivering 

sub-millimeter radiosurgical precision anywhere 

in the body 

Continual Image Guidance - Automatically track, 

detect, and correct for tumor and patient 

movements throughout the treatment 

Respiratory Motion Tracking - Delivering tightly 

contoured beams synchronized precisely 

with tumor motion 

Unrivaled Conformality - Enabling safe and 

e�ective dose escalation with an unhindered 

non-coplanar workspace 

Unique Radiosurgical Expertise - Providing new 

options to more patients with capabilities only 

available from the CyberKnife System 

With the CyberKnife System, you can make 

untreatable and unreachable tumors a thing 

of the past – o�ering new hope to more patients. 

Visit us at ESTRO in booth B04:42. 

Information > www.estro.be 

No Stereotactic Frames - No Fiducials - No Gantry Mobility Restraints 

Donald 

Acoustic Neuroma & 

Prostate Cancer 

CyberKnife Patient 

Treated May 1999 & 

November 2005

Radiotherapy &Oncology Radio &O - Estro-members.org

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