1. Treatment Guidelines for Pre-operative Radiation Therapy for Retroperitoneal Sarcoma: Preliminary Consensus of an International Expert Panel EH Baldini, D Wang, CN Catton, DJ Indelicato, DG Kirsch, C Deville, C Le Pechoux, R Haas, IA Petersen, K May, D Roberge, BA Guadagnolo, B O'Sullivan, R Abrams, TF DeLaney

2. None of the authors have disclosures

3. Background The role of RT for extremity soft tissue sarcoma is well established However, the role of RT for retroperitoneal sarcoma (RPS) is unproven

4. EORTC 62092-22092 (STRASS Trial) RPS: Randomize Pre-Op RT Surgery Ongoing, results are eagerly anticipated

5. Background In the meantime, many centers recommend Pre-op RT for RPS after multidisciplinary discussion But, there are no RT guidelines for this approach

6. Purpose To define radiation treatment guidelines for Pre-operative RT for RPS

7. RT Treatment Nomenclature GTV: Gross Tumor Volume CTV: Clinical Target Volume –Expansion of GTV to include areas at risk for harboring potential microscopic disease PTV: Planning Target Volume –Expansion of CTV to account for daily patient set-up inaccuracies and/or patient movement Treatment Field Borders –Extend beyond the PTV by about 7mm to deliver full dose to PTV

8. Extremity Soft Tissue Sarcoma RT Treatment Guidelines* CTV GTV + 4 cm proximal/distal, 1.5 cm radial Edit CTV at bone PTV CTV + 5-10mm per institutional standard *Haas, IJROBP 84:572; 2012 GTV: red CTV: green PTV: orange 4 cm 1.5 cm

9. GTV, CTV, PTV Note the CTV is edited at the bone interface

10. GTV  CTV Expansions Vary by Tumor TumorGTV  CTV Expansion Lymphoma0 mm Prostate Cancer5-7 mm Lung Cancer7 mm Glioblastoma Multiforme2 cm beyond edema Extremity STS1.5 cm radial 4 cm proximal/distal Retroperitoneal Sarcoma?

11. Methods An expert panel of 15 academic radiation oncologists who specialize in sarcoma was convened Panel members reached consensus recommendations following several meetings, conference calls and email correspondence

12. Expert Panel: US Institutions (10) Dana-Farber/Brigham & Women’s Hospital Massachusetts General Hospital Medical College of Wisconsin University of Florida, Jacksonville Duke University University of Pennsylvania Mayo Clinic Roswell Park Cancer Institute MD Anderson Cancer Center Rush University

13. Expert Panel: European and Canadian Institutions (4) Canada –Princess Margaret Cancer Centre –McGill University Health Centre France –Institut Gustave Roussy Netherlands –Netherlands Cancer Institute

14. Results Consensus Recommendations

15. Essential Collaboration between Surgeon + Radiation Oncologist Discuss resection margins of concern Discuss potential resection of kidney, liver – If nephrectomy is planned: »Adequate contra-lateral renal function should be documented »Minimize dose to contra-lateral kidney – If partial liver resection is planned: »Minimize dose to remaining liver

16. Radiation Simulation Oral and IV contrast is optional Assessment of 4D motion (4D CT) –Strongly recommended for tumors above iliac crest to define GTV4D Contour GTV on the planning CT –Register planning CT with diagnostic CT or MR T1 contrast images if necessary

17. CTV Definition Expand GTV symmetrically by 1.5 cm Edit CTV: Bone: 0 mm Bowel and Air Cavity: 5 mm Renal and Hepatic interfaces: 2 mm Skin Surface: 3-5 mm If tumor extends through inguinal canal, add 3 cm distally (as per extremity STS) If 4D CT is not performed, larger expansions are necessary for upper abdominal tumors

18. PTV Definition Expand CTV by 5mm –If frequent volumetric soft tissue imaging will be performed to confirm set-up accuracy (i.e. cone beam CT) Expand CTV by 9-12 mm –If no volumetric imaging is performed to confirm set-up

19. Dose 5040 cGy 180 cGy fractions 5 ½ weeks

20. RPS Contours GTV CTV PTV

21. RPS IMRT Graphic Plan Iso-dose Levels 100% 70% 95% 50% 80% 30%

22. Dose-Painting Radiation Boost to High Risk Margins CONCEPT: Deliver boost dose of RT to areas of tumor at risk for positive margins after resection Along posterior abdominal wall, pre-vertebral space, major vessels High Risk Boost Volume GTV

23. Dose-Painting Radiation Boost to High Risk Margins Efficacy is unproven Technique is under investigation May be considered, particularly on protocol –DeLaney Phase I/II Multi-Center Dose- Painting Boost, Dose-Escalation Trial

24. Organ at Risk (OAR) Constraints ORGANCONSTRAINT LiverMean Dose < 26 Gy Stomach and DuodenumV45<100%, V50<50%, Max 56 Gy Kidney: if one will be resectedV18 < 15% remaining kidney Kidney: if both will remainMean dose < 15 Gy, V18 < 50% Spinal CordMax Dose 50 Gy Small & Large Bowel (Bowel Bag)V45 < 195 cc RectumV50 < 50% TesticlesV3 < 50%, Max Dose < 18 Gy OvaryMax Dose < 3 Gy Femoral HeadMax Dose < 50 Gy, V40 < 64%

25. Treatment Technique Intensity modulated radiation therapy (IMRT) preferred unless OAR constraints can be met with 3D-conformal technique

26. Conclusion Consensus guidelines were achieved and are recommended for use –To establish uniformity of treatment –Aid future efficacy and toxicity assessment

27. Thank You Tom DeLaney Dian Wang Charles Catton Danny Indelicato David Kirsch Curt Deville Cecile Le Pechoux Rick Haas Ivy Petersen Kilian May David Roberge Ashleigh Guadagnolo Brian O’Sullivan Ross Abrams