IMRT for Head and Neck Tumors
This house believes that the use of
Functional Imaging for treatment
planning of head and neck tumors
needs to be carefully considered.
Vincent GREGOIRE, M.D., Ph.D., Hon.
FRCR
Head and Neck Oncology Program, Radiation Oncology Dept.
& Center for Molecular Imaging and Experimental
Radiotherapy, Université Catholique de Louvain, St-Luc
University Hospital, Brussels, Belgium
AAPM
Aug. 2011
PTV 69 Gy Oropharyngeal SCC
Larynx
PRV Spinal cord
Right parotid
PTV 55.5 Gy
T2-N0-M0
SIB-IMRT: 30x2.3 Gy
30x1.85 Gy
Left parotid
AAPM
Aug. 2011
Heterogeneity in H&N TV
delineation
This house believes that …
• RO will be (even more) multidisciplinary…
• RO is conformal (e.g. IMRT, proton, hadrons)…
• RO will be tailored (individualized) (based on imaging
and molecular profiling) and adaptive …
• RO will be associated with targeted agents …
AAPM
Aug. 2011
AAPM
Aug. 2011
Harari et al., 2004
Target selection and delineation
Betrayal of
images
This is not an
apple…
R. Magritte
Segmentation methods: one by
lab…!
Manual
delineation
Visual interpretation
Subjective approach!
Visual rendering
Histogram-based
Fixed threshold (SUV, %)
Adaptive threshold (SBR)
Soft thresholding (probabilistic)
Complex model – unrecoverable target
Feature-based
(Fuzzy) clustering
Clustering of TAC
Image-based
Probabilistic modeling
Gradient based
AAPM
Aug. 2011
AAPM
Aug. 2011
∆ Experimental conditions
∆ Data sets
∆ Validation studies
NO CONSENSUS
Macroscopy
5 cm
5 cm
Variability in PET image segmentation
for H&N tumors …
5 cm
CAT Scan
18F-FDG
PET
AAPM
Aug. 2011
Schinagl et al., 2007
AAPM
Aug. 2011
Daisne et al, 2003
From PET image to tumor: a fixed
threshold?
Image-Guided Radiation Therapy in HNSCC
The 4th dimension …
FDG-PET
GTV (ml)
Surgical
Specimen
40%
50%
1
2
3
4
5
6
7
8
9
8.3
5.2
30.9
4.1
5.6
8.6
17.3
15.4
24.3
23.3
10.9
29.7
8
37.9
9.7
35.9
41.8
39.9
11.8
6.7
21.7
5.3
19.2
6.6
25.5
28.3
30
55.1
55.7
38.6
57
70.9
43.2
59
67.5
56.5
mean
13.3
26.5*
17.2
55.9
Patient
AAPM
Aug. 2011
0 Gy
50 Gy
Geets et al, 2006
PET image segmentation during
RxTh
AAPM
Aug. 2011
Geets et al, 2003
PET in radiotherapy planning for NSCLC
Pathological correlation?
Clinical validation?
UG 4mm
Raw image
SBR
Image processing
Image segmentation
BG 6mm + deconvolution
NSCLC with atelectasis
W&C
AAPM
Aug. 2011
J. Lee & X. Geets, 2005
AAPM
Aug. 2011
Deruysscher, 2007
NSCLC digital MC PET phantom
Different segmentation methods …
AAPM
Aug. 2011
Werner-Wasik et al., 2011
PET in radiotherapy planning for NSCLC
AAPM
Aug. 2011
PET in radiotherapy planning for NSCLC
Wanet et al., Radioth. Oncol. 2011
Methods
Objective evaluation of the available
segmentation methods
Statistical methods
Gradient detection
Images
Simulated PET images (MC)
Pathology validated patient images
Clinical image used as an example
and associated segmentation
NCAT
+
+
=
Figures of merit
Scanner model
AAPM
Aug. 2011
Wanet et al., Radioth. Oncol. 2011
AAPM
Aug. 2011
Zubal
NURBS surface
3D phantom
3D tumor model
Precision
Shape/volume
Simulated 3D PET
Accuracy
Reproducibility/robustness
AAPM TG211, 2011
PET imaging: a wide range of
molecular probes
A word of caution …
• Glucose metabolism
18F-FDG
• Protein synthesis
11C-MET
18F-FET
hypoxia
• Proliferation
18F-FLT
• Hypoxia
proliferation
18F-FMISO
18F-FAZA
perfusion
• Receptors
18F-FES
68GA-Traztuzumab (HER2)
64Cu-DOTA-panitumumab (EGFR)
5 µm
AAPM
Aug. 2011
Courtesy of Geets, 2011
AAPM
Aug. 2011
From Kaanders., 2001
Effect of resolution
Biological heterogeneity
[18F]-FDG
TEP
2,5 mm
Registered
autoradiography
2,0 mm
2,7 mm
3,0 mm
AR 100 µm
1,5 mm
Résolution 2.3 mm
AAPM
Aug. 2011
3,5 mm
Résolution 0.1 mm
N. Christian, 2010
AAPM
Aug. 2011
N. Christian, 2010
In Vivo experimental set-up
PET-tracer, Hoechst
Pimonidazole
SiHa
Micro PET
SCCVII
Autoradiography
(2-D distribution of FAZA)
SiHa
AAPM
Aug. 2011
FAZA autoradiogram & pimonidazol
Tumor
sectioning
Immuno-fluorescence
microscopy
(hypoxia, vessels, perfusion)
UT-SCC-33
Busk et al Acta Oncol, 2008;47:1201-1210
Busk et al IJRBOP 2008;70:1202-12
Busk et al ActaBusk
Oncol;,
2008;47:1201-1210
et al Acta
Oncol, 2008;47:1201-1210
AAPM
Aug. 2011
Busk et al IJRBOP 2008;70:1202-12
Scaling issue…
Scaling issue…
Tumor: FSA II
Mouse n° 2_1
Tum Volume: 2.30 ml
18F-FDG – 300 µCi
100
Dice Similarity Index (%)
90
Volume corresponding to the
highest 10 percent of activity
AR Volume
80
70
60
50
FSA II (n=5)
SCC VII (n=5)
FSA II + RT (n=5)
40
30
20
10
PET Volume
0
10
AAPM
Aug. 2011
Mismatch (/)
N. Christian, 2010
20
30
40
50
60
70
80
90
100
% of Overall Tumor Volume
AAPM
Aug. 2011
N. Christian, 2007
PET imaging: a wide range of
molecular probes
Effect of resolution
• Glucose metabolism
18F-FDG
• Protein synthesis
11C-MET
18F-FET
r²
• Proliferation
0.88
18F-FLT
0.84
Mosaic PET
• Hypoxia
0.86
18F-FMISO
18F-FAZA
0.87
0.86
• Receptors
0.84
18F-FES
68GA-Traztuzumab (HER2)
64Cu-DOTA-panitumumab (EGFR)
% vol
Mouse T ø
0.0
7.0
8.7
10.0
11.0
12.1
12.7
13.1
13.9
14.5
0.0
13.9
17.5
20.1
22.1
23.8
25.3
26.6
27.8
28.9
30.0
N. Christian, 2010
15.0
Human T ø
AAPM
Aug. 2011
AAPM
Aug. 2011
Comparison 18F-FDG / 14C-EF3
Courtesy of Geets, 2011
Comparison 18F-FDG / 14C-EF3
Anova: p = 0.19
AAPM
Aug. 2011
N. Christian, 2010
AAPM
Aug. 2011
N. Christian, 2010
“Dose painting” : the physics issue
“Dose painting” by number…
Flat dose
Non-flat dose
Mean Tumor Dose = 2 Gy
Survival is non-flat
(higher in resistant areas)
More similar survival
across entire tumor
AAPM
Aug. 2011
Courtesy of D. De Ruysscher
Molecular imaging dose painting by number
• Tomotherapy Hi-Art
AAPM
Aug. 2011
Molecular imaging dose painting by number
Dose escalation protocol …
• H&N SCC:
T4N2bM0
• 60 Gy + SIB of 30
Gy
• Hypoxia (Cu-ATSM)
• DPBN based on FDGPET
• Median dose of 80.9
Gy (n=7) et 85.9 Gy
(n=14)
• No grade 4 acute
toxicity
AAPM
Aug. 2011
Deveau et al., 2010
AAPM
Aug. 2011
Duprez et al., 2010
Functional imaging for H&N
treatment planning
• Great potential … but …
• Don’t trust your physician …
• Rely on user’s independent methods The Bridge
at
…
• Be aware of the various conceptual
limitations …
Argenteuil
• Never forget the clinical knowledge …
• At the end, the proof is in the pudding
…
AAPM
Aug. 2011
C. Monet, 1874