1. Barbara Vanderstraeten Ghent University Hospital 19 January 2008
What is dose painting?
Barbara Vanderstraeten
Ghent University Hospital
19 January 2008

2. Outline
Introduction
Technical solution
Planning studies
Conclusions

3. I. Introduction Anatomical vs. biological imaging
Tumor biology characterization
Biological imaging for RT
Biological Target Volume
Dose painting
By contours
By numbers

4. Imaging for RT
From V Grégoire

5. Anatomical imaging CT
MRI

6. Biological imaging
PET
SPECT
fMRI
MRSI
Brain
Tumor

7. Tumor biology characterization
Radiotracer
Characterization
18F-FDG
Glucose metabolism
18F-FLT
DNA synthesis
11C-MET
Protein synthesis
60Cu-ATSM, 18F-FMISO
Hypoxia
Radiolabeled Annexin V
Apoptosis
Radiolabeled aVb3 integrin antagonists
Angiogenesis
S Apisarnthanarax and KSC Chao. Radiat Res 2005;163:1-25.

8. Biological imaging for RT
Improvement of diagnostic and staging accuracy
Guidance of target volume definition and dose prescription
Evaluation of therapeutic response

9. Target volume definition
Gross tumor volume (GTV)
Clinical target volume (CTV)
Planning target volume (PTV)

10. Biological target volume (BTV)
Tumor burden: clonogene celdensiteit
124I IUDR (lang half-leven!)
CC Ling, J Humm, S Larson et al Int J Radiat Oncol Biol Phys 2000;47:

11. Dose painting
Over mekaar leggen; minder evident dan ik hier zeg

12. Dose painting by contours

13. Dose painting by contours
KSC Chao, WR Bosch, S Mutic et al Int J Radiat Oncol Biol Phys 2001;49:

14. Dose painting by contours
KSC Chao, WR Bosch, S Mutic et al Int J Radiat Oncol Biol Phys 2001;49:

15. Dose painting by contours
18F-FDG-PET-guided dose painting in head and neck cancer: phase I clinical trial (41 patients)
I Madani, W Duthoy, C Derie et al Int J Radiat Oncol Biol Phys 2007;68:

16. Dose painting by numbers

17. Dose painting by numbers
Biologically Conformal Radiation Therapy

18. II. Technical solution
Relationship between signal intensity and radiation dose
Treatment plan optimization
Treatment plan evaluation
Example

19. Relationship between signal intensity and radiation dose
Ilow
Ihigh
Dlow
Dhigh
Signal intensity

20. Treatment plan optimization
B Vanderstraeten et al. Phys Med Biol 2006;51:N277-86

21. Treatment plan evaluation
QVH
3-D:
2-D: QVH, “effective DVH”, “spatially-normalized DVH”
1-D:

22. Example: 18F-FDG-PET-guided BCRT for oropharyngeal cancer

23. Example: 18F-FDG-PET-guided BCRT for oropharyngeal cancer
Feasibility
Planning constraints OK
Best biological conformity for the lowest level of dose escalation

24. III. Planning studies Feasibility of BCRT
18F-FDG-PET-guided BCRT for head and neck cancer
B Vanderstraeten et al. Radiother Oncol 2006;79:249-58
18F-FMISO-guided BCRT for head and neck cancer
D Thorwarth et al. Int J Radiat Oncol Biol Phys 2007;68:

25. Feasibility of BCRT
18F-FMISO-PET-guided BCRT for a base-of-tongue cancer case
M Alber et al. Phys Med Biol 2003;48:N31-5
18F-FDG-PET- and 99mTc-MAA-SPECT-guided BCRT for 2 lung cancer cases
DK Das et al. Med Phys 2004;31:
18F-FDG-PET- guided BCRT for an oropharyngeal cancer case
B Vanderstraeten et al. Phys Med Biol 2006;51:N277-86

26. 18F-FDG-PET-guided BCRT for head and neck cancer

27. Set-up 15 head and neck cancer patients
18F-FDG-PET imaging of tumor metabolism
Dose painting by contours (“contour-based IMRT”) versus dose painting by numbers (“voxel intensity-based IMRT”)
Comparison of clinically relevant dose-volume characteristics
Between “cb250” and “vib ”
Between “vib ” and “vib ”
DVHs

28. Target dose prescription
“cb250”
(cGy/fx)
“vib ”
“vib ”
PTVPET
250
PTV69+PET
PTV69
216
PTV66
206
PTV62
194
PTV56
175

29. “cb250” (blue) versus “vib216-250” (green)

30. “vib216-250” (green) versus “vib216-300” (orange)

31. Example

32. Treatment plan evaluation
BCRT did not compromise the planning constraints for the OARs
Best biological conformity was obtained for the lowest level of dose escalation
Compared to dose painting by contours, improved target dose coverage was achieved using BCRT

33. 18F-FMISO-guided BCRT for head and neck cancer
13 head and neck cancer patients
18F-FMISO-PET hypoxia imaging
Comparison of
Conventional IMRT
18F-FDG-PET-guided dose painting by contours
18F-FMISO-PET-guided dose painting by numbers
DVHs, TCP

34. 18F-FMISO-guided BCRT for head and neck cancer
D Thorwarth, SM Eschmann, F Paulsen and M Alber Int J Radiat Oncol Biol Phys 2007;68:

35. IV. Conclusions The rationale for dose painting is clear
Dose painting is technically feasible
By contours
By numbers
Current issues?
See Discussion at 12:30
Biological imaging
PET and SPECT
DCE-MRI, BOLD MRI, MRSI
Requirement for precise treatment delivery (IGRT)
Inter-fraction tumor tracking
Anatomical and biological changes during RT
Clinical trials

37. Radiobiology Nuclear medicine Radiotherapy physics Radiotherapy
Fundamental research in vitro, animal studies
Radiobiology
Biological imaging
Tracers
Acquisition, reconstruction, quantification
Treatment planning and delivery
Biological optimisation
Adaptive RT
Treatment outcome
Nuclear medicine
Radiotherapy physics
TRANSLATIONAL RESEARCH = translation of scientific discoveries into practical applications
Radiotherapy
Clinical investigations