PET/CT for radiotherapy planning of head-‐neck cancer

Dr. Wouter V. Vogel
Department of Nuclear medicine
Department of Radia3on oncology
NKI-­‐AVL, Amsterdam, NL
PET/CT for
radiotherapy planning
of head-­‐neck cancer

Disclosure slide
! Research Support: none
! Consultant: none
! Speakers Bureau: none
! Honoraria and/or Stockholder: none
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Topics
! Why PET/CT ?
! Diagnos3c value
! Tumor delinea3on
! Tumor characteriza3on
! How to do it
! Requirements
! Image fusion
! Collabora3ons
! Radia3on protec3on
! Future perspec3ve
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Required informaAon
! Loca3on
! Type
! Size
! Volume
! Mucosal spread
! Deep infiltra3on
! Node metastases
! Distant metastases
! Stage
! Pa3ënt characteris3cs
! HPV / EBV
! Et cetera …
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Anatomical imaging with CT
Based on Assue density
! Anatomical orienta3on
! Recogni3on / delinea3on of cri3cal normal organs
! Recogni3on / delinea3on of tumor loca3ons
! Required for RT planning electron density map
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A mulAmodality diagnosis
Clinical evaluaAon
! History
! Inspec3on
! Biopsies
! Experience
???
tumor
AddiAonal imaging
! Ultrasound
! (ce)MRI
! DWI, spectroscopy
! Endoscopy, et cetera
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Molecular imaging
! Is a visual func3on test
! Does not provide borders
of 3ssues, but borders of
func3ons
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FDG PET/CT
for selecAon of radiotherapy

Reasons to perform PET/CT
! Does the pa3ent have cancer ?
! Where is it located, and what stage ?
! Is radiotherapy appropriate ?
! Op3mizing the treatment
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Finding a primary tumor
DetecAon rate FDG PET aIer negaAve convenAonal work-­‐up
! 25% Rusthoven, Review, Cancer 2004
! 29% Johansen, DAHANCA-­‐13, Head Neck 2008
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Are there nodal metastases?
DetecAon of nodal disease
! Meta-­‐analysis of 32 studies
! Sensi3vity 81-­‐90%
! Specificity 89-­‐90%
PET outperforms CT and MRI for
detec3on of node metastases in
the neck, and it is the best non-­‐
invasive instrument available
Impact on treatment
! Upgrade elec3ve nodal field areas to high dose RT
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Characterizing extra findings
Coin lesion FDG PET/CT
! Sensi3vity 97%
! Specificity 79%
Impact on treatment
! Nega3ve Follow-­‐up
! Posi3ve Biopsy
(or treatment)
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Are there distant metastases?
For the presence of M1 disease
! Sensi3vity 93%
! Specificity 96%
Impact on treatment
! Swith RT from cura3ve to
pallia3ve intent in 15% of cases
afer M0 conven3onal workup.
Na3onal Ins3tute for Clinical Excellence (NICE). Lung cancer: the
diagnosis and treatment of lung cancer. In: Clinical Guideline No.: 24.
NICE Web site. 2005
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Conclusion
! FDG-­‐PET/CT is important for radiotherapy
before you even started
Examples of diseases where RT treatment
is currently selected with PET/CT
! Lung cancer
! Head-­‐neck
! Lymphoma
! Gynaecological
! Melanoma
! Breast cancer (recurrence)
! Prostate cancer (recurrence, choline)
! Brain tumors (methionine)
! … et cetera
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MulAmodality
more than nice colors ?

Understanding molecular imaging
The informa3on of molecular imaging on its own
can be virtually meaningless
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MulAmodality: the greater perspecAve
The informa3on of molecular imaging on its own
is virtually meaningless
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Imaging modaliAes
1895 X-­‐ray Wilhelm C. Röntgen
1940 Fluorescence microsc. Coons and Kaplan
1946 NMR spectroscopy F. Bloch and E. Purcell
1948 Ultrasound George Ludwig
1953 ScinAgraphy Hal Anger
1963 SPECT Kuhl and Edwards
1970 PET Brownell
1973 MRI Paul Lauterbur
1975 CT Robert S. Ledley
1979 US doppler Geoff Stevenson
New techniques never replace old ones,
we are just ge\ng more opAons.
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Planar image fusion
1953 Thyroid scin3graphy and photograph of a pa3ent
1960 Bonescan and X-­‐rays
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Common pracAce today
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Radiotherapy
what do we need?

TherapeuAc raAo
100%
Effect
Tumour control
Slide 23
Normal tissue damage
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Increase therapeuAc raAo
• Increase tumour sensitivity to irradiation
• eg add chemotherapy, decrease hypoxia
• Decrease normal tissue sensitivity to irradiation
• eg amifostine
• Increase conformality of irradiation
• Focus on tumour
• Avoid organs at risk
This is where PET comes into play
Slide 24
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GTV
Gross Tumor Volume
based on:
Imaging modalities
Diagnostic modalities
(pathology/histology)
Clinical examination
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CTV
Clinical Target Volume
GTV with margin
accounting for sub-clinical
microscopic extension
This volume needs to be
treated accurately to
assure treatment efficacy.
e.g.: CTV=GTV+0.5 cm
CTV is a anatomicalclinical
volume
Slide 26
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PTV
Planning Target Volume
CTV encompassed with
margin for:
Organ motion
Daily patient setup
Machine setup
Intra-treatment
variations
…
PTV is a geometrical
concept
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RT planning process
Item
Item 1
• Item 2
• Item 3
Slide 28
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RT planning process
Radiotherapy requires a uniform dose distribution within the tumor.
Target dose uniformity within +7% and -5% of the prescribed tumor dose.
While sparing surrounding normal tissues
To achieve this goal multiple beams are used
Main steps in Treatment Planning
1. Define treatment volumes and risk organs
2. Define optimal beam setup
3. Calculate dose distribution within the patient
and treatment times per beam
4. Plan evaluation
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Sources of errors
Inaccurate beam data
Wrong monitor unit calibration
Inaccurate beam measurements
Wrong beam geometry
Slide 30
Accuracy of volume definition
With advanced treatment techniques only voxels labeled as tumor will be
irradiated
Target volume delineation becomes extremely important
Inter- and Intra-observer variations should be mimimized
Accuracy of image fusion
Patient repositioning
Image registration CT / MR / PET
Data transfer/consistency between RTP and Linac
And many more potential problems...
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The result we try to get
You need CT
! Anatomical reference
! Tumor delinea3on
! Electron density map
PaAent benefit
! Bener cura3on/survival
! Less side-­‐effects
! Bener quality of life
PET imaging adds
! Sensi3ve tumor detec3on
! Discrimina3on tumor / benign
! Consistent tumor delinea3on
! Quan3fy tumor characteris3cs
Impact on planning
! Improve planning accuracy
! Higher dose to tumor
! Lower dose to normal 3ssues
! (Adapt to tumor characteris3cs)
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PotenAal problems
PET/CT imaging can cause
! FN: missing tumor 3ssue
! FP: including benign 3ssues
! Misposi3on tumor 3ssue
! False tumor characteris3cs
ResulAng in
! Decreased curaAon/survival
! More side-­‐effects
! Reduced quality of life
Impact on planning
! Degrade planning accuracy
! Reduce effec3ve dose to tumor
! Increase dose to normal 3ssues
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Technical
requirements

StandardizaAon of PET/CT imaging
! Indica3ons
! Pa3ent prepara3on
! Image acquisi3on
! Image reconstruc3on
! Viewing
! Quan3fica3on
! Delinea3on
! Repor3ng
! Impact
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PET for radiaAon oncology
! Large bore
! Flat table
! Laser posi3oning
! Posi3oning aids
! Planning CT
! (4D gated)
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AddiAonal paAent posiAoning
Repeated posiAoning is not a problem !
Modality Repeats
! Planning CT / MR 1 – 2
! Addi3onal PET (/CT) 1
! Radia3on treament 25 – 50
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Required accuracy
Small errors in pa3ent (re)posi3oning are expected,
and are compensated with a margin around the GTV.
This is the PTV.
Acceptable PTV margins
depend on the body part
! Head/neck ~ 5 mm
! Colorectal ~ 10 mm
! Lungs ~ 20 mm
craniocaudal
PosiAoning or image fusion errors on PET/CT
should not exceed the standard PTV margins
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Head/neck
Required
! Flat table
! Customised head/neck support
! Personalised mask
! Mask clamps
! Knee support
! (Laser guides)
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Example: NO MASK
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Example: NO MASK
Please don’t
try this at
home
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Example: SubopAmal mask placement
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Example: SubopAmal mask placement
Validate your new
approach and skills
with experts
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Well-­‐trained personnel
RecommendaAons
! Accept a learning curve for pa3ent posi3oning
! Collaborate with radiotherapy department staff
! Train a dedicated PET planning staff
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Example: Success
Results
! Image registra3on error < 3 mm (Vogel et al, JNM 2007)
! Correla3on of lesions < 5 mm possible
! PTV margins 0.5 cm
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Tumor contouring
using a PET signal

DelineaAon: a mulAmodality procedure
Clinical evaluaAon
! History
! Inspec3on
! Biopsy, histology
! Experience
AddiAonal imaging
! Ultrasound
! (ce)CT
! (ce)MRI, DWI, spectro
! Endoscopy, et cetera…
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What does FDG PET show ?
The signal comes from
! Cells that proliferate
! Cells that have de-­‐differen3ated
! Cells that have high Glut-­‐1 expression
! Cells that are hypoxic
PET iden3fies voxels that
contain a lot of cells, that
tend to be radioresistent
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What does FDG PET not show ?
Volumes with a low
concentraAon of
vital tumor cells
! Microscopic extent
! Superficial spread
! Diffuse infiltra3on
! Necro3c parts
! (Well-­‐differen3ated
tumor parts)
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What volume do you need to know?
From a surgical point of view
! All tumor
From a biological point of view
! All tumor mee3ng certain diagnos3c criteria
! All tumor relevant for a treatment decision
From a radiotherapeuAc point of view
! PTV The total volume to be irradiated
! CTV The clinically relevant area, likely to contain tumor
! GTV All known tumor containing areas
! Boost A biological subvolume of the tumor volume
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PET for GTV
GTV involves all known tumor locaAons
! GTV involves all known tumor loca3ons
! PET does not show them all
! PET does not provide the GTV
! PET can contribute to GTV defini3on, just like any other scan
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DelineaAon methods
Available strategies
! Visual / manual
! SUV
! % of tumor ac3vity
! % of background ac3vity
! Ra3o tumor -­‐ background
! Advanced algorithms
This choice is not trivial !
! Resul3ng volume depends heavily on the method
! There is insufficient valida3on for all methods
! At least a fixed SUV threshold is not suitable
! A “best method” is currently not iden3fiable
Schinagl et al., IJRBOP 2007
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Impact on volumes
Method
! GTV 40 53.6 mL
! GTV bg 94.7 mL
! GTV vis 157.7 mL
! GTV 2.5 164.6 mL
(Nestle, JNM 2005)
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FDG PET versus pathology
Every technique
has issues
! False posi3ves
! False nega3ves
! Limited resolu3on
! Non-­‐linearity
! Mul3-­‐factorial signal
! Interpreta3on issues
Tumor volume in pharyngolaryngeal
squamous cell carcinoma: comparison at CT,
MR imaging, and FDG PET and valida3on
with surgical specimen.
Daisne et al. Radiology. 2004;233(1):93-­‐100
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A visual mulAmodality approach
x
! x
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Reduce interobserver variaAon
Observer varia3on in target volume delinea3on of lung cancer related to radia3on
oncologist-­‐computer interac3on: a 'Big Brother' evalua3on. Steenbakkers RJ et al.
Radiother Oncol. 2005 Nov;77(2):182-­‐90.
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Interobserver variaAon – No PET
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Interobserver variaAon – With FDG-­‐PET
Huge improvement !
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StandardizaAon of delineaAon
! Delinea3on algorithm
! Image reconstruc3on
! Color scales
! Protocols
Whatever you choose, it will instantly fail when
! Switching from 3D to 4D in lung cancer
! Buying a new PET scanner
! Using a different tracer
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Non-­‐homogeneous PET
PET oIen does not represent the tumor as a whole, and will not
replace CT, MR, or other means to find tumor volume and borders
PET can be used to idenAfy a biological subvolume
Defining Radiotherapy Target Volumes Using (18)F-­‐Fluoro-­‐Deoxy-­‐Glucose Positron
Emission Tomography/Computed Tomography: S3ll a Pandora's Box?
Devic S et al. Int J Radiat Oncol Biol Phys. 2010 Jun 18.
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PET for Boost definiAon
A boost field involves an important tumor subvolume
! A boost is required for areas with
! A high number of cells to kill
! Rela3vely radioresistent cells (hypoxia)
! FDG PET shows exactly those areas
! PET can define a boost area
When PET dictates the shape of a high-­‐dose RT field,
the procedure needs to be highly standardized!
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Day-­‐to-­‐day problems
Scans have different characterisAcs with regard to
! Image resolu3on, par3al volume effects, blurring
! Involuntary pa3ent mo3on, swallowing
What is the truth ???
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Day-­‐to-­‐day problems
Factors leading to significant tumor locaAon differences in mask
! Positron drif (2-­‐5 mm)
! Pa3ent mo3on (swallowing)
What is the truth ???
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Summary of delineaAon
Who needs PET for volume definiAon ?
! GTV delinea3on when difficult on CT/MR/clinical evalua3on
! Boost defini3on in scien3fic research
And how to do it?
! Be aware of the limita3ons of PET
! GTV: No definite strategy yet, use a holis3c approach
! Boost: Prefer automa3c, use one algorithm and s3ck to that
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Moving from
tumor contouring
to
biological evaluaAon

Contouring a signal
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Claude Monet
Impression, Sunrise
(1874)
Considered to be
the first
impressionist
pain3ng

From where to what
The Roman Dodecahedra
Courtesy U. Nestle, Freiburg
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What are we currently NOT doing ?
InterpretaAon of the biological acAvity inside the GTV/boost
! Op3mal dose ?
! Op3mal frac3ona3on scheme ?
! Inhomogeneous treatment ?
! Radiotherapy the best choice ?
! Radiosensi3zers needed ?
! Is the tumor responding ?
! Adapt or switch treatment ?
! Adjuvant chemo or surgery ?
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FDG uptake predicts RT outcome
[18F]fluorodeoxyglucose uptake by positron emission tomography predicts outcome of non-­‐small-­‐cell lung cancer.
Sasaki R et al. J Clin Oncol. 2005 Feb 20;23(6):1136-­‐43.
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! Poten3al impact
on required RT
dose, but
unverified

Does the tumor respond to treatment?
Stage III NSCLC
! PET/CT 2 weeks afer CRT
PET CR
! Good prognosis
! Succesful resec3on defines outcome
PET PD
! Poor prognosis
! Resec3on no longer defines outcome
18F-­‐FDG PET for assessment of therapy response and
preopera3ve re-­‐evalua3on afer neoadjuvant radio-­‐
chemotherapy in stage III non-­‐small cell lung cancer.
Eschmann SM, EJNMMI 2007 Apr;34(4):463-­‐71.
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A different place for PET of nodes ?
Pre
! T1 N2b oropharynx carcinoma
Standard treatment
! Chemoradia3on
! RT 66 Gy / 35 frac3ons
! Cispla3na weekly 40 mg/m 2
In case of residual nodes
! Addi3onal neck dissec3on
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A different place for PET of nodes ?
Pre 12 weeks
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Complete metabolic
response 12 weeks
afer treatment
What does this
mean ?

A different place for PET of nodes ?
Pre 12 weeks 1 year
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ScienAfic evaluaAon
! 112 pa3ents with (chemo)radia3on for a N2 headneck tumor
! FDG-­‐PET/CT scan 3 months afer CRT
! Only FDG-­‐posi3ve necks received node dissec3on
! All others wait-­‐and-­‐see
! Average follow-­‐up 2,5 years
Results
! 50 pa3ents with residual nodes on CT
! 9 posi3ve on PET: PPV = 22%
! 41 nega3ve on PET: NPV = 100%
Results of a prospec3ve study of positron emission tomography-­‐directed management of residual nodal abnormali3es in node-­‐posi3ve
head and neck cancer afer defini3ve radiotherapy with or without systemic therapy.
Porceddu SV et al., Head Neck 2011. (Aus)
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PotenAal impact
! Less opera3ons needed afer CRT
! Quality of life bener afer cura3on
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Different biological pathways
Planning CT FDG FAZA
Anatomy Metabolism Hypoxia
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PET for imaging of
the delivered RT dose

Radionuclide therapy
Iodine MIBG
We can
! SEE our treatment
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! Verify the predicted distribu3on
! Quan3fy the given radia3on dose

External beam radiotherapy
! Looks very well guided
! But is based on predic3ons
and indirect measurements
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Protons vs photons
Protons have a sharp
energy release profile
Courtesy D. Schaart, TU Delf, the Netherlands
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Uncertain proton range
! Proton depth is very exact
Beam Beam
! But may change with tumor reduc3on during treatment
! This threatens the safety of the procedure
Courtesy D. Schaart, TU Delf, the Netherlands
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Place a PET in the proton beam setup
Visualise and quan3fy
energy release DURING
(or very shortly afer)
proton treament !
Courtesy D. Schaart, TU Delf, the Netherlands
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In-­‐line PET images
Image quality is s3ll limited, but quan3fica3on seems valid
Courtesy D. Schaart, TU Delf, the Netherlands
Prediced dose Measured PET
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Dr. Wouter V. Vogel
Nuclear medicine physician
NKI-­‐AvL, Amsterdam, the Netherlands
Thank you
for your arenAon