Workshop on Advanced Technologies in Radiation Oncology

1. Workshop on Advanced Technologies in Radiation Oncology Howard Sandler

2. Prostate Cancer • Model for use of advanced technologies • Common, long follow-up, simple geometric relationship to critical structures

3. Dose Limiting Toxicity • Rectal toxicity • What about bladder?

4. Garg, et al. IJROBP 66:1294,2006

5. GU Morbidity Late Morbidity from Early Proton Study – median FU 13 yrs Gardner, et al. MGH J Urol167:123,2002 GI Morbidity

6. 50.4 photon + 16.8 photon 50.4 photon + 25.2 CGE proton Shipley, et al. IJROBP 32:3,1995

7. RTOG 9406?

9. RTOG 9406 • 1084 patients from 34 institutions • 36% had neoadjuvant hormonal rx • By dose level, 5 yr OS is 89%, 87%, 88%, 89%, [95%*] * 3-yr OS

10. RTOG 9406 – Biochemical Results

11. RTOG 9406 – Toxicity

12. RTOG 9406 – Toxicity • Grade 3+ • By dose level • 4%, 4%, 5%, 7%, 10%

14. DVH Dose- Volume Histogram

15. Grade ≥2 Rectal Morbidity at 70 Gy Huang, et al MD Anderson IJROBP 54:1314,2002

16. Rectal Bleeding Requiring Laser Treatment or Transfusion (3DCRT) Peeters et al. IJROBP 61:1019, 2005

17. Peeters et al. IJROBP 64:1151, 2006

18. LKB Modelling of Dutch Study – Uses Entire DVH n = 0.13, TD50 81 Gy, m = 0.14, p=0.025 Peeters et al. IJROBP 66:11, 2006

19. Rectal Constraint

20. 64 Gy 3 field Conv – open Conf – 16 mm GTV-block margin 90% coverage HD vol reduced by 40% Bladder toxicity NS

22. Modelling Data from Marsden Trial • Dose-surface histograms • 79 pts available • Physical dose converted using α/β=3 • 1000 points per contour (= points per slice) Fenwick, et al IJROBP 49:473–480, 2001

25. Randomized Trials • Of higher dose vs. lower dose?

26. PROG 9509 T1b-2b prostate cancer PSA <15ng/ml • Trial design • No hormonal therapy r a n d o m i z a t i o n Proton boost 19.8 GyE Proton boost 28.8GyE 3-D conformal photons 50.4 Gy 3-D conformal photons 50.4 Gy Total prostate dose 79.2 GyE Total prostate dose 70.2 GyE

27. Zietman, et al. JAMA2005;294:1233-1239

28. Morbidity? Zietman, et al. JAMA2005;294:1233-1239

29. Dutch Study Points • ASTRO no backdating • 21% had hormonal rx • 0 mm post PTV marginfrom 68-78 Gy • Dose prescribed toisocenter Peeters et al. JCO 24:1990,2006

31. Randomized Trials • Of altered fractionation vs. standard fractionation?

32. Hypofractionation

33. Hypofractionated Randomized Trial • 16 Canadian regional centres • 66 Gy in 33 fx vs. 52.5 Gy in 20 fx (2.62) • Simple conformal rx • Non-inferiority design with abs diff 7.5% Lukka, et al. JCO 23:6132,2005

34. 7% worse in short arm

35. RTOG 0415 Schema 73.8 Gy/41 Fx T1c-2a GS <7 PSA <10 70 Gy/28 Fx n=800 Endpoint is 5 Year BFFF Non-inferiority margin 7% (Control 85%, Exp 78%)

36. Other Hypofractionation Randomized Trials • CHHIP (Conv or Hypo High Dose IMRT) • N=2200 • 3 arm study • Standard vs. 2 hypofractionated arms

37. Randomized Trials • Particle vs. photon? • No PSA era trials • MGH proton, RTOG neutron

38. Particle Therapy • Protons • Bragg peak • Concerns • ‘Wide’ penumbra due to scattering • Neutron dose unless proton IMRT (scanned beam) is used (from p,n reaction)

39. Carbon Ion • Higher LET - ?Better for more “resistant” tumors • ?Fewer fractions needed “The promising results obtained with carbon radiotherapy need confirmation in controlled clinical trials with large patient numbers comparing carbon ion RT with photon IMRT and proton RT taking also into account toxicity and quality of life.” Schulz-Ertner, et al Radiation Therapy With Charged Particles Semin Radiat Oncol 16:249,2006

40. Future Technologies/Areas for Study • Particle therapy • Carbon vs. Proton vs. Photon IMRT • Hypofractionation • Can the low α/β model for prostate be verified? • NTCP modelling • Randomized trials can help • Target motion • Issue for all externally delivered, highly conformal dose approaches