1. PET and Radiotherapy for Head and
Neck Cancer: today and tomorrow…
Vincent GREGOIRE, M.D., Ph.D.
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
MAESTRO
Jan. 2007

2. Potential added-value of PET in oncology
S / RxTh / CH
Work-up-staging
prognostic evaluation
GTV/CTV
Selection/delineation
Functional Image-guided
IMRT
Early response
FDG evaluation
C-methionine
EF3 - F-miso - CuATSM Final response
BFU - FLT evaluation
… Early detection
of recurrence
MAESTRO
Jan. 2007

3. Imaging in radiotherapy:
… today and tomorrow …
• Selection of Target Volumes with FDG-PET
• Delineation of GTV with FDG-PET
• Selection / delineation of CTV
MAESTRO
Jan. 2007

4. The use of FDG-PET for the selection of
Target Volume: setting the scene
Laryngeal SCC: T2-N1-M0
Q: unilateral vs bilateral
neck irradiation?
A: highly sensitive
examination
MAESTRO
Jan. 2007

5. Detection of metastatic disease in the neck
• N=106 patients
• oral cavity tumors
• Neck dissection for all patients (2196 lymph nodes)
Sensitivity Specificity Accuracy NPV PPV
PET 70% 82% 75% 71% 81%
CT 66% 69% 70% 66% 74%
MRI 64% 69% 66% 62% 71%
US 84% 68% 76% 79% 75%
MAESTRO
Jan. 2007 Stuckensen et al., 2000

6. Potential added-value of PET in oncology
Comparison between CT and FDG-PET for nodal staging.
Site Sensitivity Specificity
CT FDG-PET CT FDG-PET
Head and neck cancer 36-86% 50-96% 56-100% 88-100%
NSC lung cancer 45% 80-90% 85% 85-100%
Cervix carcinoma 57-73%1 75-91% 83-100%1 92-100%
Esophageal cancer 11-87% 30-78% 28-99% 86-98%
1
CT or MRI
MAESTRO
Jan. 2007 Grégoire, 2004

7. Potential added-value of PET in oncology
Comparison between PET and PET/CT for N staging (n=260)
Sensitivity (%) Specificity (%) PPV NPV
PET/CT 92 93 88 94
PET+CT 88 89 83 92
PET 85 88 82 90
CT 64 83 70 79
MAESTRO
Jan. 2007 Antoch et al., 2004

8. Target
MAESTRO
Jan. 2007 J. John, 1974

9. The Gross Tumor volume (GTV)
MAESTRO
Jan. 2007 Daisne et al., Radiology, 233: 93-100, 2004

10. The Gross Tumor volume (GTV)
MAESTRO
Jan. 2007 Daisne et al, 2004

11. From PET image to tumor: a fixed threshold?
GTV (ml)
Patient Surgical 40% 50%
Specimen
1 8.3 23.3 11.8 55.1
2 5.2 10.9 6.7 55.7
3 30.9 29.7 21.7 38.6
4 4.1 8 5.3 57
5 5.6 37.9 19.2 70.9
6 8.6 9.7 6.6 43.2
7 17.3 35.9 25.5 59
8 15.4 41.8 28.3 67.5
9 24.3 39.9 30 56.5
mean 13.3 26.5* 17.2 55.9
MAESTRO
Jan. 2007 Geets et al, 2006

12. Functional imaging and automatic
segmentation
Volume delineation based on automatic thresholding with 18F-FDG
MAESTRO Daisne et al, 2003
Jan. 2007 Geets et al, 2004

13. Imaging modalities, TVs and dose distribution
MAESTRO
Jan. 2007

14. Image-Guided Radiation Therapy in HNSCC
Impact of imaging modality on CTV/PTV delineation
Larynx/hypopharynx (n=9) Oropharynx (n=10)
200
Average (± sem) volume (cc)
CT-scan 250 CT-scan
Average (± sem) volume (cc)
FDG-PET FDG-PET
150 200
ANOVA: p<0.05 ANOVA: p<0.01
150
100
100
50
50
0 0
GTV CTV PTV GTV CTV PTV
MAESTRO
Jan. 2007 Geets et al, 2003

15. Image-Guided Radiation Therapy in HNSCC
Impact of imaging modality on dose distribution
MAESTRO
Jan. 2007 Geets et al, 2006

16. Conformal radiotherapy and IMRT
in Head and Neck Tumors
DAHANCA: http://www.dshho.suite.dk/dahanca/guidelines.html
EORTC: http://www.eortc.be/home/ Radio/EDUCATION.htm
MAESTRO RTOG: http://www.rtog.org/hnatlas/main.htm
Jan. 2007

17. CT-based delineation of lymph node levels in
the neck: Brussels- Rotterdam consensus guidelines
Level II
Ant. submandibular gland
post. belly of digastric m.
Post. sternocleidomastoid m.
LII Lat. sternocleidomastoid m.
Med. paraspinal m.
int. carotid artery
LV
Cra. lateral process of C1
Cau. hyoid bone
MAESTRO
Jan. 2007

18. Imaging in radiotherapy:
… today and tomorrow …
• Atlases
• Adaptive Target Volume delineation
• Non-rigid registration
• Adaptive dose distribution
• Other PET tracers
MAESTRO
Jan. 2007

19. H&N IMRT practice heterogeneity
Atlases?
MAESTRO
Jan. 2007 Harari et al., 2005

20. CT MRI (T2) FDG-PET
PRE-R/
(Week 2)
WEEK 3
(Week 4)
WEEK 5
MAESTRO
Jan. 2007

21. Biological adaptive IMRT
Before R/ Week 1 Week 2 Week 3 Week 4 Week 5 Week 6 Week 7
R/ start
Images acquisitions
CT MR T2 FS MR T2 FDG-PET
Anatomic imaging Dynamic FDG-PET
• 10 patients with stage III-IV pharyngo-laryngeal SCC treated by CT -RT
• Images acquired before R/ and during RT after means doses of 14, 25, 35
and 45 Gy.
MAESTRO
Jan. 2007 Geets, 2006

22. PET image segmentation during RxTh
UG 4mm
Raw image
SBR
Image processing Image segmentation
MAESTRO
Jan. 2007 Lee & Geets 2006

23. PET image segmentation during RxTh
UG 4mm
SBR
Raw image
Image processing Image segmentation
BG 6mm + deconvolution
W&C
MAESTRO
Jan. 2007 Lee & Geets 2006

24. PET image segmentation
Patient Surgical Threshold- Gradient-based
No specimen based method method
 Phantom images
1 4.1 8.7 4.7
 Synthetic phantom images
2 5.2 7.4 5.5
 Jaszczak phantom (6 spheres) 3 5.6 16.3 8.2
 Patient images 4 15.4 37.2 19.7
 Total laryngectomy 5 17.3 35.4 25.3
(surgical specimen is frozen,
frozen, 6 24.3 34.1 25
sliced, 7 30.9 33.4 27.8
digitized, delineated, and registred) mean 14.7 24.7* 16.6**
* in comparison with surgical specimens, p = 0.014 (Student’s t-test)
** in comparison with surgical specimens, p = 0.19 (Student’s t-test)
MAESTRO
Jan. 2007 Lee & Geets 2006

25. Impact on TV delineation
P<0.001
MAESTRO
Jan. 2007 Geets, 2006

26. Impact on TV delineation
Classic CT-based planning Adaptive PET-based planning
P<0.001
Planning V10 V50 V80 V90 V95 V100
Classic CT-based 100% 100% 100% 100% 100% 100%
Adaptive CT-based 99% 100% 100% 85% 80% 66%
Classic PET-based 99% 99% 98% 83% 82% 81%
Adaptive PET-based 99% 100% 98% 73% 67% 58%
MAESTRO
Jan. 2007 Geets, 2006

27. Image registration…
Reference
image
Rigid
registration
Non-rigid
registration
MAESTRO Loeckx & Maes
Jan. 2007 ESAT, 2004

28. Image registration…
Week 0 Week 3
30 Gy SIB
MAESTRO
Jan. 2007 Parraga, Castadot & Lee, 2006

29. Image registration…
Differential dysplay
MAESTRO
Jan. 2007 Parraga, Castadot & Lee, 2006

30. Image registration…
Week 3 Week 3 on week 0
Non-rigid
Registration
(Samba)
MAESTRO
Jan. 2007 Parraga, Castadot & Lee, 2006

31. Dose registration…
Time 1 (t1)
Deformed checkerboard
showing the non- rigid Deformed dose at t1
transformation from t1 to t2 Deformed contour on CT at t2
Time 2 (t2)
MAESTRO
Jan. 2007 Lee, 2006

32. Other PET tracers…
Hypoxia: 18F-EF3
Metabolism: 18F-FDG
11C-Met
Proliferation: 76Br-BFU
MAESTRO
Jan. 2007

33. From microscopy to PET images…
CT-scan MRI
µPET-scan Autoradiography
MAESTRO
Jan. 2007 N. Christian, 2006

34. Conclusions: future challenges …
• Target Volume selection and delineation
• Adaptive IMRT: geometrical, biological & dosimetrical
•which imaging modalities??
•which biological pathways??
•which volume/dose registration algorithms??
•how frequently??
• Clinical validation
MAESTRO
Jan. 2007

35. Acknowledgements
• Communication and Remote Sensing Lab. Alois du BOIS d’AISCHE, Eng.
Pierre-François d’HAESE, Eng.
Benoit MACQ,Eng., Ph.D.
• ENT and Head & Neck surgery Marc HAMOIR, M.D.
Philippe ROMBAUX, M.D.
• Imaging Emmanuel COCHE, M.D.
Thierry DUPREZ, M.D.
Max LONNEUX, M.D.
• Oral & Maxillo-Facial surgery Pierre MAHY, M.D.
Hervé REYCHLER, M.D., D.M.D.
• Pathology Birgit WEYNAND, M.D.
• PET laboratory Anne BOL, Ph.D.
Daniel LABARE, Ph.D.
• Radiation Oncology Nicholas CHRISTIAN, M.D.
Jean-François DAISNE, M.D., Ph.D.
Xavier GEETS, M.D.
John LEE, eng., Ph.D.
Pierre SCALLIET, M.D., Ph.D.
MAESTRO
Jan. 2007 Milan TOMSEJ, M. Sc.

36. Acknowledgements
• KULeuven, Radiation Oncology Karin HAUSTERMANS, M.D., Ph.D.
Sarah ROELS, M.D.
Tom DEPUYDT, Ph.D.
Pieter SLAGMOLEN, Eng.
• KULeuven, ESAT Frederic MAES, Eng., Ph.D
Frederic LOECKX, Eng.
MAESTRO
Jan. 2007

37. Target selection and delineation
Betrayal of images
This is not an
apple…
R. Magritte
MAESTRO
Jan. 2007

38. MAESTRO
Jan. 2007 R. Wouters, 1915

39. Image-Guided Radiation Therapy in HNSCC
Impact of imaging modality on dose distribution
CT-based target volume FDG PET-based target volume
MAESTRO
Jan. 2007

40. IMRT in Head and Neck Tumors
Left parotid Hypopharyngeal SCC
PTVs
T4-N0-M0
Dose: 25 x 1.8 Gy bid
Spinal cord Right parotid
MAESTRO
Jan. 2007

41. Watershed & Clustering segmentation
1.Raw images 2.Image denoising 3.Image deblurring 4.TAC distances
c/s c/s c/s
Bil. PSF
XYZ
D
T XYZ XYZ T
Image improvement 5.Watersheds
D
XYZ
9.Segmented images 8.Cluster Analysis 7.TAC distances 6.Wat.sh. mean TACs
c/s
c/s
XYZ
D T
T T
MAESTRO
Jan. 2007

42. Image-Guided Radiation Therapy in HNSCC
The 4th dimension …
FDG-PET
0 Gy
50 Gy
MAESTRO
Jan. 2007 Geets et al, 2003

43. Bayesian terminology for diagnostic imaging studies
Disease status
“-” “+”
Test “-” TN FN NPV = TN/TN+FN
“+” FP TP PPV = TP/TP+FP
Sensitivity = TP/TP+FN
Specificity = TN/TN+FP
Disease Disease
“-” “+” “-” “+”
“-” 48 2 NPV = 96% “-” 25 25 NPV = 50%
Test
“+” 20 30 PPV = 60% Test “+” 4 46 PPV = 92%
Sensitivity = 94% Sensitivity = 65%
MAESTRO Specificity = 70% Specificity = 86%
Jan. 2007

44. From microscopy to PET images…
Mean minimal distance Mean angle (°)
between two skew lines
MR-CT: 0.21 0.06 mm 2.23 0.31
PET-CT: 0.23 0.11 mm 2.52 0.74
PET-MR: 0.28 0.07 mm 2.47 0.46
PET-AR: 0.18 0.04 mm 3.53 0.39
MAESTRO
Jan. 2007 N. Christian, 2006

45. Work in progress: other tracers…
PET-FLT
FLT ?
FDG
0 Gy 20 Gy Before surgery
MAESTRO
Jan. 2007 Lee & et al,
HaustermansGeets 2006

46. Gradient Intensity Image
Image saturation (window level)
Raw image
Grad. Int. image
MAESTRO Boundaries do not move! Lee & Geets 2006
Jan. 2007