1. Pelvic Breakout Group

2. Purpose of meeting What is current status of radiation oncology technologies today. Where should we invest research resources to best understand value of technology Biology questions can be addressed parallel to technology usage –Preop rectum—examine tissue effects –IMRT low doses QA, training, education—is required to optimally implement new technology Clinical trials are necessary to evaluate technology

3. KEY QUESTION 1 The raison d’etre for the advanced technologies is to increase the dose to the cancer without increasing toxicity, or deliver the same dose as conventional technology but with less toxicity. QUESTION: In which cancers is there the most pressing need for new technology for increasing the dose or decreasing the toxicity?

4. KEY QUESTION 1 The raison d’etre for the advanced technologies is to accurately target and improve our understanding when we increase the dose to the cancer without increasing toxicity, or deliver the same dose as conventional technology but with less toxicity. QUESTION: In which cancers is there the most pressing need for new technology for increasing the dose or decreasing the toxicity? Targeting is just as important as dose. If you give high doses but miss, you have failed

5. In which cancers is there the most pressing need for new technology for increasing the dose or decreasing the toxicity? Prostate—remains an important public health problem. Dose matters but is >80Gy necessary? Postop prostate—what is the CTV? Nodal target volumes are important in all pelvic malignancies. What is best way to define (PET, MR-LG, RaAb) Cervix—what is the CTV? MR guided brachytherapy Rectal Cancer—IMRT for short course RT 5x5Gy

6. In which cancers is there the most pressing need for new technology for increasing the dose or decreasing the toxicity? Prostate –Important public health problem –Local control remains problematic –Dose escalation to Subclinical disease Rectum –Dose to small bowel –Interactions of systemic therapy and XRT –Biomarkers and interaction with XRT Cervix –Opportunity for adaptive (change plan) RT –Interactions of systemic therapy and XRT –Dose to small bowel What is the CTV for primary and nodal drainage –PET, MR-LG, Labeled antibodies, etc…

7. In which cancers is there the most pressing need for new technology for increasing the dose or decreasing the toxicity? Should we dose escalate subclinical disease? e.g. 75Gy to the PAN What about the role of systemic therapy when we intensify local therapy? Biomarkers and their interactions with radiation therapy—tailored dose escalation –Cervix, rectum, prostate Cervix an opportunity for adaptive radiation therapy trial (image guidance) –Change plan to eliminate brachytherapy (response based)?

8. KEY QUESTION 2 Demonstrating improved ANTICIPATED dose distributions (in-silico or in phantoms) only generates the hypothesis that a new technology may be superior. To prove that hypothesis, we must demonstrate - by controlled clinical trials - a clinically meaningful increase in survival and/or decrease in toxicity. QUESTION: What clinical trials are the most important for demonstrating a meaningful benefit to patients?

9. What clinical trials are the most important for demonstrating a meaningful benefit to patients? Prostate—phase III trial with QOL endpoints –Might be too soon to study, once organ motion and delivery uncertainties are resolved…if RadOnc community demands it. Prostate High risk—phase II trial –Nodal RT (IMRT) and further dose escalation + HT Rectum—phase II trials –Biological endpoints –QOL Cervix—Phase I/II trials –Biological correlates –QOL

10. What clinical trials are the most important for demonstrating a meaningful benefit to patients? Fractionation opportunities in all sites QOL should be allowed as a primary endpoint in phase III trials

11. KEY QUESTION 3 Demonstrating improved ACTUAL dose distribution in the patient could be useful in phase I/II trials. QUESTION: What technological developments are required for demonstrating ACTUAL dose distribution in-vivo?

12. What technological developments are required for demonstrating ACTUAL dose distribution in-vivo? Dose modeling (with validated calculation methods) –Exit fluence –Deformation –Tracking of accumulated dose Activated PET measures Implanted dosimeters Elimination of systematic error—can this be studied in a clinical trial Cannot underestimate need to verify dose delivery—20% rule!

14. KEY QUESTION 4 Other clinical or biological intermediate end-points may be useful in clinical trials. QUESTION: What might those intermediate end-points be (and what lessons have we learned regarding their pitfalls from PSA, etc?)

15. What might those intermediate end-points be (and what lessons have we learned regarding their pitfalls from PSA, etc?) PSA Phoenix/ASTRO definition Pathologic CR in rectal cancer PET imaging for rectum, cervix –FLT, F-Miso during XRT –FDG pre and post XRT –MRS for cervix MRI/MRS post RT for Prostate Serum and fresh tissue banking –Genomics, Proteomics