Gli Aspetti Tecnologici dell'Adroterapia - C.R. ENEA Frascati
Gli Aspetti Tecnologici dell'Adroterapia - C.R. ENEA Frascati
Gli Aspetti Tecnologici dell'Adroterapia - C.R. ENEA Frascati
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<strong>Gli</strong> <strong>Aspetti</strong> <strong>Tecnologici</strong> dell’Adroterapia<br />
Parte 1<br />
Sandro Rossi<br />
Fondazione CNAO<br />
Corso teorico-pratico sull’adroterapia: l’alta tecnologia applicata alla clinica<br />
CNAO, Pavia, 17-18 Maggio 2013
Introduzione: il razionale dell’adroterapia<br />
Stato dell’arte: il Centro Nazionale di Adroterapia Oncologica<br />
Panoramica: la tecnologia e attività di R&S
Adroterapia consente di trattare casi “difficili”<br />
PRECISIONE<br />
EFFICACIA<br />
Tumori vicini ad organi critici<br />
Tumori radioresistenti,<br />
che non rispondono<br />
alla radioterapia convenzionale
Direzione del fascio di radiazioni nella materia<br />
Precisione dell’adroterapia<br />
Posizione del<br />
tumore
Adroni: irraggiamento conforme<br />
Larghezza del tumore<br />
5
Adroni: irraggiamento conforme<br />
Raggi-X (IMRT) – 9 campi Protoni – 1 campo
(M. Belli et al.)<br />
Ioni Carbonio: efficacia biologica<br />
4<br />
3<br />
2<br />
1<br />
RBE<br />
1 10 100 LET<br />
10 – 20 keV/µm = 100 – 200 MeV/cm =<br />
20 – 40 eV/(2 nm)<br />
Ridotta dipendenza da presenza di ossigeno<br />
7
Patologie trattate con ioni carbonio al NIRS di Chiba
Terapia con Raggi-X (fotoni di 5 – 20 MeV)<br />
Protonterapia<br />
In Italia: 120'000 pz/anno<br />
Categoria A: pazienti elettivi = 1'000 pz/anno<br />
Numero di potenziali pazienti<br />
Categoria B: probabili vantaggi = 12'000 pz/anno<br />
Terapia con ioni carbonio<br />
% tumori radioresistenti 1'500 pz/anno<br />
(Commissione Ministero della Salute – Anno 2009)<br />
Si giustifica il CNAO (ca. 2000 paz/anno)<br />
e in prospettiva altri centri per protoni
Prevista dal Ministero della Salute<br />
Art. 92 della Legge 23 dicembre 2000, n. 388<br />
Insediata il 21 Novembre 2001
•L’età media<br />
•45% femmine<br />
•55% maschi<br />
Oggi al CNAO lavorano 90 persone<br />
48%<br />
• Ingressi di<br />
personale<br />
nel triennio<br />
2010 -2012
NAZIONALI<br />
Fondazione TERA: progetto definitivo, specifiche alta tecnologia, ricerca<br />
INFN: co-direzione AT, > 15 task tecnici, ricerca e formazione<br />
Università di Milano: coordinamento medico e formazione<br />
Università di Pavia: task tecnici, radiobiologia e formazione<br />
Università di Catania: fisica medica<br />
IL CNAO ESEMPIO DI SISTEMA<br />
LA RETE DI COLLABORAZIONI<br />
Università del Piemonte Orientale: attività mediche<br />
Politecnico di Milano: posizionamento paziente, radioprotezione<br />
Istituto Europeo di Oncologia: attività mediche, autorizzazioni<br />
Fondazione Ospedale San Matteo di Pavia: attività mediche, logistica<br />
Comune di Pavia: terreno e autorizzazioni<br />
Provincia di Pavia: viabilità e autorizzazioni
INTERNAZIONALI<br />
CERN (Geneva): task tecnici, progetto PIMMS<br />
GSI (Darmstadt): linac e componenti speciali<br />
LPSC (Grenoble): ottica, betatrone, low-level RF, sistema di controllo<br />
Med-Austron (Vienna): collaborazione tecnica per il centro MA<br />
Roffo Institute (Buenos Aires): attività mediche<br />
NIRS (Chiba): attività mediche, radiobiologia, formazione<br />
HIT (Heidelberg): attività di ricerca<br />
IL CNAO ESEMPIO DI SISTEMA<br />
LA RETE DI COLLABORAZIONI
Le fasi del CNAO<br />
Fase 0: organizzazione Anni: 2002 - 2004<br />
Fase 1: costruzione Anni : 2005 - 2009
Giugno 2005
19 Novembre 2009<br />
7 Novembre 2005<br />
La costruzione del CNAO è terminata a fine 2009<br />
16
Le aree del CNAO<br />
Espansione per gantry:<br />
spazio sufficiente per<br />
contenere due gantry simil-HIT<br />
meeting<br />
rooms<br />
conference<br />
room<br />
direction offices<br />
Centrale elettrica<br />
(132 kV --> 15 kV)<br />
(2 x 20 MVA)<br />
library<br />
Circa 3500 mq<br />
Futuro Bld.<br />
della ricerca:<br />
circa 2000 mq
Il sincrotrone per protoni e ioni carbonio
Hospital based: safety, efficiency, reliability, maintainability<br />
High Energy<br />
Transfer<br />
Lines<br />
Linac<br />
Ion Sources<br />
Synchrotron<br />
Treatment<br />
Rooms
Starting point… THE PATIENT<br />
Hospital based: safety, efficiency, reliability, maintainability<br />
1 Beam particle species p, He 2+ , Li 3+ , Be 4+ , B 5+ , C 6+ , O 8+<br />
2 Beam particle switching time ≤ 10 min<br />
3 Beam range<br />
1.0 g/cm 2 to 27 g/cm 2 in one treatment room<br />
3.1 g/cm 2 to 27 g/cm 2 in two treatment rooms<br />
Up to 20 g/cm 2 for O 8+ ions<br />
4 Bragg peak modulation steps 0.1 g/cm 2<br />
5 Range adjustment 0.1 g/cm 2<br />
6 Adjustment/modulation accuracy ≤± 0.025 g/cm 2<br />
7 Average dose rate 2 Gy/min (for treatment volumes of 1000 cm 3 )<br />
8 Delivery dose precision ≤± 2.5%<br />
9 Beam axis height (above floor)<br />
150 cm (head and neck beam line)<br />
120 cm (elsewhere)<br />
10 Beam size 1<br />
4 to 10 mm FWHM for each direction<br />
independently<br />
11 Beam size step 1 1 mm<br />
12 Beam size accuracy 1 ≤± 0.25 mm<br />
13 Beam position step 1 0.8 mm<br />
14 Beam position accuracy 1 ≤± 0.2 mm<br />
15 Field size 1<br />
16 Field position accuracy 1 ≤± 0.5 mm<br />
17 Field dimensions step 1 1 mm<br />
18 Field size accuracy 1 ≤± 0.5 mm<br />
(Basic specifications of CNAO facility)<br />
5 mm to 34 mm (diameter for ocular treatments)<br />
2×2 cm 2 to 20×20 cm 2 (for H and V fixed beams)
4 (Cortesia Aprile 2008 di Siemens Medical)<br />
(Cortesia di GSI)<br />
Tecnica di<br />
irraggiamento<br />
sistema attivo
Le fasi del CNAO<br />
Fase 0: organizzazione Anni: 2002 - 2004<br />
Fase 1: costruzione Anni : 2005 - 2009<br />
Fase 2: sperimentazione Anni: 2010 - 2013<br />
Fase 3: funzionamento Anni : 2014 …
Certificazione di qualità: ISO 9001 e ISO 13485
Dosimetry and Radiobiology<br />
Preventive intercomparison CNAO vs INT-MI<br />
with X-rays (linac 6 MV, 2 Gy): difference < 0.1%<br />
(in collaborazione con gruppi radiobio INFN)<br />
Field10x10 cm 2 ,<br />
33x33 spots,<br />
scanning step 3 mm<br />
(16 energie)
Results Survival curves of cells crypts<br />
in 3 SOBP positions<br />
Facility Beam D10 (Gy) Variance RBE10 Variance<br />
position<br />
D10<br />
(%)<br />
Cobalt-60<br />
γ rays<br />
--- 14.86±0.08(*)<br />
NIRS Proximal 10.38 (+) 1.44 (*)<br />
Middle 9.46(+) 1.57(*)<br />
Distal 8.29(+) 1.80(*)<br />
GSI Proximal 10.21(+) 1.47(*)<br />
Middle 9.40(+) 1.63(*)<br />
Distal 8.37(+) 1.80(*)<br />
CNAO Proximal 9.85 5.1 % NIRS 1.51 4.7% NIRS<br />
3.5% GSI<br />
2.7 % GSI<br />
Middle 9.75 3.1% NIRS 1.52 3.18% NIRS<br />
3.7% GSI<br />
6.7% GSI<br />
Distal 8.5 2.5% NIRS 1.75 2.78% NIRS<br />
1.5% GSI<br />
2.78% GSI<br />
Carbon beam at CNAO is biologically<br />
identical to the ones in NIRS and GSI<br />
(difference in RBE < 7%)
PROTONI<br />
22 Settembre 2011: il trattamento del primo paziente
13 Novembre 2012: 1°paziente con ioni Carbonio al CNAO<br />
Recidiva locale di carcinoma adenoideo cistico<br />
12 frazioni da 4.1 GyE , 4 frazioni a settimana, 49.2 GyE totali.<br />
Boost di ulteriori 4 frazioni da valutare in base a tolleranza.<br />
3 campi in IMPT
Ioni<br />
Carbonio Protoni<br />
Abruzzo 1<br />
Basilicata 1<br />
Calabria 1 1<br />
Campania 2<br />
Emilia Romagna 3 4<br />
Lazio 6<br />
Liguria 2 4<br />
Lombardia 7 12<br />
Marche 2<br />
Piemonte 1 7<br />
Puglia 1 6<br />
Sardegna 1<br />
Sicilia 1 2<br />
Toscana 3 6<br />
Veneto 3 3<br />
Totale complessivo 22 58<br />
Provenienza geografica pazienti arruolati<br />
12<br />
11<br />
10<br />
9<br />
8<br />
7<br />
6<br />
5<br />
4<br />
3<br />
2<br />
1<br />
0<br />
Ioni Carbonio Protoni
La fase di funzionamento<br />
I trattamenti saranno effettuati nell’ambito del Sistema<br />
Sanitario Nazionale e una rete consentirà il reclutamento<br />
efficiente dei pazienti<br />
A regime il CNAO arriverà a trattare circa 2000 pazienti<br />
per anno<br />
Una sala sperimentale sarà realizzata al CNAO e tempo<br />
fascio sarà dedicato ad attività di ricerca clinica,<br />
radiobiologica e traslazionale
European Network for LIGht ion Hadron Therapy
Expansion and Research spaces integrated in facility layout<br />
Extra space to host 2 C-gantries<br />
(Partial underground level of CNAO)<br />
Laboratories and<br />
research spaces<br />
Experimental Room<br />
Project of research beamline<br />
ready fall 2013<br />
Beam line devoted to clinical,<br />
radiobiology and physics research<br />
(collaboration with INFN)
Tecnologia e attività di R&S:<br />
Accelerators Technology<br />
Dose Delivery Systems<br />
Gantry for carbon ions<br />
Patient positioning and dose verification<br />
Imaging and software<br />
ACKNOWLEDGMENTS: U. AMALDI<br />
Panoramica<br />
(Useful ref.: U. Linz Ed., Ion Beam Therapy, Springer 2011 and refs therein)
Loma Linda University Medical Center: first patient 1992<br />
First hospital based<br />
protontherapy centre<br />
(1992)<br />
2009:160 sessions/d<br />
7m<br />
synchrotron<br />
Optivus Ltd. commercialises this centre
45,000<br />
40,000<br />
35,000<br />
30,000<br />
25,000<br />
20,000<br />
15,000<br />
10,000<br />
5,000<br />
0<br />
Research centres<br />
Protontherapy is booming<br />
40,000 patients<br />
> 84 000 patients<br />
22 PT centers<br />
Hospitals<br />
1950 1960 1970 1980 1990 2000 2010<br />
Carbon Ions: > 9000 patients; 6 centres (+2 planned)<br />
45<br />
40<br />
35<br />
33 centres<br />
(+16 planned)<br />
30<br />
25<br />
20<br />
15<br />
10<br />
5<br />
0
EPAC - 30 June 2006<br />
IBA<br />
Protontherapy: a market exists …<br />
Mitsubishi<br />
Varian<br />
Hitachi<br />
37
Coming up: Single room facility<br />
250 MeV synchrocyclotron rotating around the patient<br />
MEVION S250<br />
Superconducting SC<br />
Diameter 1.8 m
Expansion in 2010<br />
HIMAC<br />
Heavy Ion Medical Accelerator in Chiba<br />
(First patient in 1995)<br />
Superconducting<br />
gantry<br />
Carbon Ion facilities<br />
2 synchrotrons 800 MeV/u,<br />
therapy and nuclear physics<br />
Japan: Hyogo + Gunma – (China Lanzhou 2013+Shangai 2014)
Ion-<br />
Sources<br />
Synchrotron<br />
LINAC<br />
Treatment halls by<br />
Siemens Medical<br />
HIT - Heidelberg<br />
First patient: end 2009<br />
So far about 1.000 patients<br />
High Energy Beam Transport Line<br />
Quality<br />
Assurance<br />
Gantry
Med-Austron (based on CNAO/INFN design + DDS)<br />
• 3 ion sources for phase 1 (one additional source possible)<br />
• Pre-accelerator – RFQ & IH Linac<br />
• Main accelerator – synchrotron (77 m circ.) CNAO/CERN/PIMMS design<br />
• Extraction line<br />
• Irradiation rooms: research: horizontal,<br />
medical: horizontal & vertical, horizontal, proton-gantry
New medical accelerators (?): IBA Superconducting cyclotron<br />
700 tons
+ Simplicity of fixed field<br />
+ Potential for fast (ms) variable energy<br />
+ Rapid cycling (200 Hz, repainting)<br />
- High intensities<br />
- Multistage accelerators<br />
- Complicated magnets<br />
- Complicated RF cavity<br />
- Dense lattice (ext. diff.)<br />
New medical accelerators (?): FFAG<br />
(original idea dates back to 1950’s)<br />
Only existing reasearch facility: KURRY 150 MeV proton scaling FFAG
New medical accelerators (?): BNL fast cycling synchrotron<br />
30 Hz repetition rate (repainting?)<br />
Fast energy change<br />
(first publication 1999’s, S. Peggs et al.)<br />
Injection linac at 8 MeV/u<br />
Racetrack, FODO in the arcs, D=0 ss<br />
Fast inj+extr, C = 60 m<br />
(from D. Trbojevic et al. IPAC2011)
150 MeV/u<br />
Source EBIS - SC<br />
Cyclotron K 600 - SC<br />
200 tons<br />
Linac CCL @ 5.7 GHz<br />
16 modules<br />
RF power<br />
system<br />
New medical accelerators (?): TERA cyclinac for C-ions<br />
16 Klystrons<br />
(P peak = 12 MW)<br />
Linac for Image Guided Hadron<br />
THerapy LIGHT 150-400 MeV/u<br />
CABOTO =<br />
CArbon BOoster for<br />
Therapy in<br />
Oncology<br />
400 MeV/u<br />
Energy is adjusted in 2 ms in the full range by changing the power pulses sent to the<br />
accelerating modules<br />
Charge in the spot is adjusted every 2 ms with the computer controlled source<br />
300 Hz
Technology status and R&D:<br />
Accelerators Technology<br />
Dose Delivery Systems<br />
Gantry for carbon ions<br />
Patient positioning and dose verification<br />
Imaging and software<br />
Panoramica
Methods for imparting the dose with carbon ions:<br />
layer stacking (NIRS+Japan)<br />
Wobbling and multileaf collimator adapted<br />
to transverse shape of each slice<br />
(energy changed with synchrotron and range shifter)<br />
Conformation, components activation, secondary neutrons
Methods for imparting the dose with carbon ions:<br />
active scanning: “raster scanning” à la GSI (HIT+CNAO)<br />
The synchrotron beam is moved<br />
continuously<br />
Energy changed with the synchrotron<br />
NIRS decided recently to adopt the active scanning
Slow extraction<br />
Bucket channeling<br />
Ripples<br />
Beam<br />
0 V<br />
Improvements:<br />
beam extraction optimization<br />
High-density,<br />
slow -moving<br />
Extracted beam<br />
Low-density,<br />
fast moving<br />
Transverse<br />
beam size<br />
Resonance<br />
lines<br />
x, ∆p/p, Qh<br />
Intensity dinamic range: ≈1000<br />
FWHM = 4-10 mm<br />
Intensity ripple (∆I/I) ≤ ± 20% at 2 kHz<br />
(extraction with a betatron core - PIMMS)<br />
50 ms
“Minimal” choice: breathing synchronisation<br />
(already applied in Chiba and HIT)<br />
Interesting also for IMRT:<br />
lots of efforts and devices<br />
(Review in Riboldi et al, Lancet Oncology 2012)<br />
Improvements: On-line imaging<br />
External surrogates with<br />
correlation models<br />
X-rays<br />
(Courtesy of Medical Intelligence)<br />
Ultrasound, MRI<br />
Particle radiography
GSI approach<br />
p +1 or C +6<br />
Improvements: tumour tracking with active scanning<br />
Tranverse<br />
variation<br />
4D<br />
Energy<br />
variation
Monitoring system (CNAO)<br />
Double system of ICs:<br />
(integral, stripX,Y) – (integral, pixel)<br />
Two measures: Intensity, Position, Profile<br />
Redout frequency: 1 MHz (integral),<br />
10 kHz (strip, pixel)<br />
Resolution: 0.1 mm strip, 0.2 mm pixel<br />
Area: 20 x 20 cm2<br />
Non uniformity < 1%<br />
Short term stability < 0.3%<br />
(NIMA 698 (2013) 202-207) Issue: monitoring spots of C-ions at low intensity
Technology status and R&D:<br />
Accelerators Technology<br />
Dose Delivery Systems<br />
Gantry for carbon ions<br />
Patient positioning and dose verification<br />
Imaging and software<br />
Panoramica
PSI proton gantry<br />
(Courtesy M. Pullia)<br />
Comparison of dimensions<br />
GSI carbon ion gantry
(Courtesy T. Haberer)<br />
Main Parameters<br />
Diameter [m] 13<br />
Length [m] 25<br />
Overall weight [t] 600<br />
Maximum power [kW] 600<br />
Rotational weight [t] 420<br />
Maximum allowed deformation [mm] 0,5<br />
Heidelberg ion gantry: unique in the World!<br />
First patient October 19 th , 2012
Bmax = 2.88 T<br />
Gmax = 9.0 T/m<br />
HIMAC superconducting gantry is in construction<br />
Combined function magnets:<br />
bending and focusing (BM1 ~ BM6)<br />
(Courtesy T. Murakami)<br />
B and G changing vs cycle<br />
Scanning magnets at<br />
the middle point<br />
Combined function magnets (BM9 ~ BM10)<br />
-> square irradiation field<br />
-> parallel beams
Novel gantry for carbon ions<br />
The ULICE WP6 collaboration realized a conceptual design of a mobile isocenter gantry,<br />
• Innovative layout<br />
• Cheaper and simplified mechanical structure<br />
• Less magnets in the gantry line<br />
Rationale for the choice<br />
• Total weight reduced as well as deformations<br />
• Well known magnet technology<br />
• Layout scalable to SC magnets
Project in progress by CEA (France) in collaboration with IBA<br />
12.2 tons<br />
B = 5 tesla<br />
Two layer helical wires<br />
on a straight cylinder<br />
give a dipole field<br />
(S. Caspi et al.)<br />
ISSUES: field quality for scanning beams;<br />
changing fields (energy) for active scanning<br />
90° magnet following a design<br />
by INFN-Genoa and TERA<br />
Project in progress at LBL - Berkeley
Technology status and R&D:<br />
Accelerators Technology<br />
Dose Delivery Systems<br />
Gantry for carbon ions<br />
Patient positioning and dose verification<br />
Imaging and software<br />
Panoramica
High precision devices for patient positioning<br />
(Treatment room #1 at CNAO)
3D Real-time IR Optical Tracking (OTS)<br />
• Real time reconstruction of spherical markers<br />
and surfaces<br />
• Sub-millimeter accuracy : peak 3D errors
Projectile<br />
Pre-collision Post-collision<br />
12 C<br />
Atomic nucleus<br />
of tissue<br />
16 O<br />
15 O<br />
11 C<br />
Dose visualisation: “in beam PET”<br />
Projectile fragment<br />
Neutron<br />
Target fragment<br />
Courtesy of GSI<br />
[kGy]<br />
D ose<br />
]<br />
Counts [10<br />
3<br />
6<br />
4<br />
2<br />
0<br />
5<br />
0<br />
Dose<br />
Activity<br />
β +<br />
0 50 100 150 200<br />
Depth [mm]<br />
ISSUES: low statistics;<br />
blood flow dilution;<br />
off-line PET logistics
Proton Range Radiography (PRR)<br />
Secondaries emission and reconstruction<br />
Electronic telescope for the measure of position and residual range of<br />
protons; it gives the density map of the traversed volumes; it permits<br />
to check in real time the treatment planning assumptions on position<br />
and dimensions of the traversed tissues and organs.<br />
Nuclear Scattering<br />
Tomography (NST)<br />
(U. Amaldi et al.)<br />
Three-dimensional map of the<br />
tissues densities obtained by<br />
vertex reconstruction of high<br />
energy protons interactions (><br />
600 MeV).<br />
Interaction Vertex<br />
Imaging (IVI)<br />
Density of interaction<br />
vertex reconstruction<br />
gives information on the<br />
Bragg peak position.<br />
PROMPT radiation (Gamma) - Enlight
Technology status and R&D:<br />
Accelerators Technology<br />
Dose Delivery Systems<br />
Gantry for carbon ions<br />
Patient positioning and dose verification<br />
Imaging and software<br />
Panoramica
1(+1) CT Medical Imaging rooms<br />
CNAO – Surface Level<br />
NIRS - 30th November 2007<br />
Advanced Medical Imaging Modalities (fusion sw)<br />
1 MR (3T) room<br />
1(+1) CT-PET rooms<br />
Advanced 3D molecular imaging modalities<br />
tumour molecular profiling<br />
dose painting with different LET ions<br />
( sources and accelerators choices)<br />
(O. Jäkel, in IBT, Springer2011)
Treatment Planning System<br />
TPS is directly related to scanning modality and RBE evaluation model<br />
Need to include management of moving organs and integration of in-room imaging<br />
(TPS used at CNAO)
Siemens<br />
TPS<br />
Imaging Modalities<br />
(CT, MR, CT-PET))<br />
DICOM<br />
DICOM<br />
RT Ion<br />
PT Archive<br />
(Short-term)<br />
Oncological Information System<br />
DICOM RT Ion<br />
DICOM<br />
RT Ion<br />
DICOM<br />
PACS<br />
PPS-PVS<br />
Elekta MOSAIQ V 2.0<br />
DOP<br />
OIS<br />
Long Term Storage R&V<br />
DICOM RT Ion<br />
Management of patients data in multiple rooms: patient throughput<br />
Networking with hospitals and clinics: patient recruitment<br />
DTMI<br />
CNAO<br />
Synchrotron<br />
Control<br />
System<br />
and<br />
Dose Delivery<br />
System
Conclusioni<br />
I centri di protonterapia sono “centri commerciali” (e<br />
“single room solutions” sono in arrivo). Non si può dire<br />
altrettanto dei centri con ioni carbonio.<br />
<strong>Gli</strong> sviluppi della tecnologia in adroterapia non si limitano al<br />
settore degli acceleratori, ma investono uno spettro molto<br />
ampio di sistemi: alcuni più urgenti di altri.<br />
Collaborazioni, confronti, rete sono parole chiave per il<br />
successo dell’adroterapia e sono utili per stabilirne<br />
l’evidenza clinica (l’aumento del numero di pazienti trattati<br />
è un fattore importante) .
GRAZIE PER L’ATTENZIONE