1. Radiotherapy - the art of the invisible Terry Kehoe Consultant Clinical Scientist Head of Oncology Physics Edinburgh Cancer Centre “How to crack a walnut”

2. CRUK - Radio 5 on 10 th June 2014 50% survive 5yrs today CRUK - TI report May 2014 Addition of RT – 16% ↑ in 5yr survival Addition of CT – 2% ↑ in 5yr survival Why does so much money go into drug development? 30yrs ago – 25% 20yr target – 75%

3. 46.7% -5yr survival in the early 80’s By the end of the 80’s 5yr survival ↑ 56.3%. By mid 90’s 5yr survival ↑ to 70%. Mid ‘00‘s - 5yr survival ↑ to 85.2% Improved survival from prostate cancer over my career

4. When I started in 1979

5. Early Image Guided Radiotherapy IGRT 2004 Fiducial Markers Inserted trans rectally Images true prostate position We increased our doses safely – how?

6. Diagnostic quality imaging Modern Image Guided Radiotherapy IGRT 2009 Same Fiducial Markers Now CT capability Images true prostate position and software calculates how much to move the field to correct for it We increased our doses safely – how?

7. Why we can increase our doses safely

8. New in 2011 even better IMRT Will have all LinAcs with this arc therapy by end of 2015

10. IMRT 5½mins VMAT 1½mins

11. ~ Doubling in 5yr survival in 3½ decades No it’s been around for a century. Some people call it a “black art” perhaps its “magic” All from RT? No - 46% of prostate cancer patients receive external beam radiotherapy. Will the 85.2% 5yr survival rise? Probably. Image Guided – IMRT is best. Is it new? How do you know you are doing it right?

12. I-125 day case permanent implant

13. 2001 Classic 2-stage procedure Volume study to assess prostate size, pubic arch problems and plan treatment Good for learning curve

14. Single stop intraoperative prostate Seeds Brachytherapy ECC late 2009

15. HDR temporary implant

16. Meta-analysis of large patient studies Using % PSA progression free as an indication of survival

17. 1Patients should be separated into Low, Intermediate, and High Risk 2Success must be determined by PSA analysis 3All Treatment types considered 4Article must be in a Peer Reviewed Journal 5. Low & Intermediate Risk articles must have a min of 100 patients 6. High Risk articles, because of fewer patients, need only 50 patients to meet criteria 7. Patients must have been followed for a median of 5 years Criteria for Inclusion of Article* * Expert panel consensus

18. 7 7 5 5 22 ← Years from Treatment → CRYO 1 1 12 24 14 8 8 2 2 23 HIFU % PSA Progression Free 11 15 Protons 21 4 4 18 9 9 10 EBRT & Seeds 25 Robot RP 26 27 HDR 28 29 30 31 32 33 34 19 36 37 38 LOW RISK RESULTS Weighted 3 3 39 35 40 100 101 13 EBRT Brachy Surgery Treatment Success 103 102 6 6 16 104 105

19. 29 22 21 5 5 19 % PSA Progression Free 18 12 28 3 3 17 10 32 9 9 8 8 2 2 25 1 1 13 Protons HDR ← Years from Treatment → 15 4 4 36 37 38 + + Seeds Alone Seeds + ADT 40 Robot RP 41 42 44 43 45 46 INTERMEDIATE RISK RESULTS Weighted 7 7 11 14 20 35 34 39 23 24 16 6 6 26 33 EBRT & Seeds EBRT Surgery Brachy EBRT & Seeds Hypo EBRT EBRT, Seeds + ADT Treatment Success 30 27 47

20. 6 6 11 36 25 15 5 5 EBRT Seeds + ADT 19 30 16 20 18 29 % PSA Progression Free 17 21 8 8 9 9 22 24 26 37 41 12 Protons HDR ← Years from Treatment → 42 43 44 45 46 47 Robot RP 48 49 101 102 103 104 105 106 107 109 HIGH RISK RESULTS Weighted 10 23 35 108 4 4 2 2 31 39 32 33 34 38 EBRT, Seeds & ADT Brachy EBRT Surgery EBRT & ADT EBRT & Seeds Hypo EBRT Treatment Success 1 1 7 7 110 27 3 3 13 14 28 40 100

21. Thank you for listening

22. What other radiotherapy improvements will increase 5yr survival? SABR – similar to VMAT but 5 visits only Better planning including radiobiological systems Better knowledge of impact Physically – transit dosimetry Biologically – chip on a pill Better on-board imaging & faster delivery Ability to adapt treatment while on the couch

23. New imaging

24. Robotic delivery Protons

25. HIFU CRYO

26. Photodynamic “Nanoknife”