Introduction

2. Introduction

3. What is radiation therapy (RT)? • Cancer treatment • Tumor versus normal tissues • External photon beam RT

4. Intensity-modulated RT (IMRT) • Brahme et al. 1982 • Fluence-modulated beams • Homogeneous, concave dose distributions • Better target dose conformity and/or better sparing of organs at risk (OARs)

5. Imaging for RT

6. Anatomical imaging • CT • MRI

7. Biological imaging • PET • SPECT • fMRI • MRSI Brain Tumor

8. Tumor biology characterization Apisarnthanarax and Chao 2005

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

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

11. Biological target volume (BTV) Ling et al. 2000

12. Dose painting

13. Dose painting by contours

14. Dose painting by numbers

15. Dose painting by numbers Biologically Conformal Radiation Therapy

16. Dose calculation algorithms • Speed versus accuracy: • Broad beam • Pencil beam (PB) • Convolution/superposition (CS) • Monte Carlo (MC) • Monte Carlo dose engine MCDE Reynaert et al. 2004 Accuracy ↑ Speed ↓

17. MC dose calculation accuracy • Cross section data • Treatment beam modeling • Patient modeling • CT conversion • Electron disequilibrium • Conversion of dose to medium to dose to water • Statistical uncertainties

18. Publications

20. Dose Dhigh Dlow Signal intensity Ilow Ihigh Implementation of BCRT:Relationship between signal intensity and radiation dose

21. Implementation of BCRT: Treatment planning strategy

22. Implementation of BCRT:Biology-based segmentation tool • 2D segmentation grid in template beam’s eye view • Projection of targets (+) • Integration of signal intensities along rayline (+) • Projection of organs at risk (-) • Distance • Segment contours from iso-value lines of segmentation grid

23. Implementation of BCRT:Objective function • Optimization of segment weights and shapes (leaf positions) • Expression of planning goals • Biological: • Tumor control probability (TCP) • Normal tissue complication probability (NTCP) • Physical: • Dose prescription

24. Implementation of BCRT:Treatment plan evaluation QVH

25. Implementation of BCRT:Example • [18F]FDG-PET guided BCRT for oropharyngeal cancer • PTV dose prescription:

26. Implementation of BCRT:Example

27. Implementation of BCRT:Example

28. Implementation of BCRT:Conclusions • Technical solution • Biology-based segmentation tool • Objective function • Feasibility • Planning constraints OK • Best biological conformity for the lowest level of dose escalation

30. BCRT planning study:Set-up • BCRT or dose painting-by-numbers (“voxel intensity-based IMRT”) versus dose painting (“contour-based IMRT”) • 15 head and neck cancer patients • Comparison of clinically relevant dose-volume characteristics • Between “cb250” and “vib216-250” • Between “vib216-250” and “vib216-300”

31. BCRT planning study:Target dose prescription

32. BCRT planning study:“cb250” (blue) versus “vib216-250” (green)

33. BCRT planning study:“vib216-250” (green) versus “vib216-300” (orange)

34. BCRT planning study:Example

35. BCRT planning study:QF

36. BCRT planning study:Conclusions • 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

37. MC dose calculations in the clinic • Comparison of PB, CS and MCDE for lung IMRT • Comparison of 6 MV and 18 MV photons for lung IMRT • Conversion of CT numbers into tissue parameters: a multi-centre study • Evaluation of uncertainty-based stopping criteria • Feasibility of MC-based IMRT optimization

38. CT conversion: multi-centre study • Stoichiometric calibration • Dosimetrically equivalent tissue subsets • Gammex RMI 465 tissue calibration phantom • Patient dose calculations • Conversion of dose to medium to dose to water

39. CT conversion: example

40. CT conversion: conclusions • Accuracy of MC patient dose calculations • Proposed CT conversion scheme: Air, lung, adipose, muscle, 10 bone bins • Validated on phantoms • Patient study: Multiple bone bins necessary if dose is converted to dose to water

41. Conclusions

42. Biologically conformal RT • Technical solution • Bound-constrained linear model • Treatment plan optimization • Biology-based segmentation tool • Objective function • Treatment plan evaluation • Feasibility of FDG-PET guided BCRT for head and neck cancer

43. MC dose calculations • Individual patients may benefit from highly accurate MC dose calculations • Improvement of MCDE • CT conversion • Uncertainty-based stopping criteria • Feasibility of MC-based IMRT optimization • MCDE is unsuitable for routine clinical use, but represents an excellent benchmarking tool

44. Outlook

45. Adaptive RT:Inter-fraction tumor tracking • Anatomical & biological changes during RT • Re-imaging and re-planning • Ghent University Hospital: phase I trial on adaptive FDG-PET guided BCRT in head and neck cancer

46. Summation of DVHs Dose 1 CT 2 Dose 2 CT 1 Registration Structure 1 Structure 2 Points TPoints P Doses TP Doses Total DVH Total doses

47. Summation of QVHs PET 1 Dose 1 PET 2 CT 2 Dose 2 CT 1 Registration Registration Registration Structure 1 Structure 2 Points TPoints Disregard TPoints outside structure 2 P Q-values TP Q-values Total QVH Total Q-values

48. 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 Radiotherapy Clinical investigations