1. Retroperitoneal Sarcoma (RPS) High Risk Gross Tumor Volume Boost (HR GTV Boost) Contour Delineation Agreement among RTOG Sarcoma Radiation and Surgical Oncologists Elizabeth H Baldini MD, MPH Dana-Farber Cancer Institute/Brigham and Women’s Hospital CTOS October 16, 2014

2. Contributing Authors E Baldini, C Raut D Wang, R Abrams, K Millikan K Salerno, J Kane C Deville, G Karakousis I Petersen, M Kendrick T DeLaney, Y Chen, J Mullen W Bosch Dana-Farber/Brigham & Women’s Rush University Medical Center Roswell Park Cancer Institute University of Pennsylvania Mayo Clinic Massachusetts General Hospital Washington University Supported by grants U10CA21661, U10CA180868, U10CA180822, U10CA37422, U24CA180803 from the National Cancer Institute

3. Background Only proven curative intent treatment modality for RPS is surgery Role of pre-op RT has not been proven and is the subject of a randomized trial: EORTC STRASS 62092 In the meantime, many multi-disciplinary teams employ pre-op RT for RPS and consensus guidelines have been developed for delineation of RT target volumes* *CTOS, New York, 2013

4. Background Further, there is interest in delivering a “boost” dose of RT to high risk areas of the tumor volume judged to be at risk for positive margins following resection –This is being tested in a multi-center Phase I/II trial among several US NRG institutions (PI: DeLaney) Gross Tumor Volume (GTV) High Risk Boost Volume

5. Radiation Target Volume Definitions GTV: Gross Tumor Volume CTV: Clinical Target Volume- GTV plus adjacent areas of potential microscopic disease High Risk GTV (HR GTV): Area of GTV judged to be at high risk of positive margins after resection GTV: red CTV: yellow GTV: red HR GTV: pink

6. Background Target VolumeKappa Agreement RPS1RPS2 Gross Tumor Volume (GTV) 0.84 Almost Perfect0.92 Almost Perfect Clinical Target Volume (CTV) 0.79 Substantial0.86 Almost Perfect HR Boost Volume0.50 Moderate0.57 Moderate HR Boost Volume contour agreement was suboptimal More clarification of this boost target volume is needed Basis of the current project Variability of RPS target volume contour delineation among Sarcoma Radiation Oncologists has recently been assessed** **ASTRO, San Francisco, 2014

7. Purpose To evaluate the variability in HR GTV Boost target volume delineation among sarcoma radiation and surgical oncology teams

8. Methods Radiation planning CT scans for 3 cases of RPS were distributed to 7 radiation and surgical oncology teams GTV (gross tumor volume) and organ contours were provided Teams were asked to contour HR GTV Boost volumes for each case

9. HR GTV Boost Contour Instructions Area considered to be at high risk for positive margins following resection Generally areas of tumor located along posterior RP musculature, ipsilateral pre-vertebral space, major vessels, or organs the surgeon would leave in situ Contour 1.5 cm thick High Risk Boost Volume GTV

10. Methods: Analysis of Contour Agreement Simultaneous truth and performance level estimation (STAPLE) algorithm* Kappa statistics (yield values from -1 to +1) Kappa = -1 : complete disagreement Kappa = +1 : complete agreement Descriptive categories for interpretation of strength**  Kappa < 0 is poor  0.00 - 0.20 is slight  0.21 - 0.40 is fair  0.41 - 0.60 is moderate  0.61 - 0.80 is substantial  0.81 - 1.00 is almost perfect agreement *Warfield, IEEE Transactions on Medical Imaging 2004;23:903 ** Landis, Biometrics 1977;33:159

11. Results Each case was contoured by 7 radiation and surgical oncology teams First case: RPS 1 –De-differentiated (DD) liposarcoma (LPS) of right upper quadrant Second case: RPS 2 –Leiomyosarcoma (LMS) of left upper quadrant Third case: RPS 3 –DD LPS of left lower quadrant with extension through inguinal canal into upper scrotum

12. Results HR GTV Boost Volume Contour Agreement Kappa Agreement RPS 1: DD LPS right upper quadrant0.66 Moderate RPS 2: LMS left upper quadrant0.61 Moderate RPS 3: DD LPS left lower quadrant0.52 Moderate Slightly better agreement than prior consensus project (0.50, 0.57) Contour agreement for all cases was only moderate

13. HR GTV: Very Good Agreement RPS 2: LUQ LMS Very good contour agreement laterally along chest wall and medially along ipsilat para-vertebral space and aorta Red: GTV Other colors: HR GTV volumes

14. HR GTV: Marginal Agreement Red: GTV Other colors: HR GTV volumes RPS 3: LLQ DD LPS Marginal contour agreement medially along bladder and anteriorly along anterior abdominal wall

15. HR GTV: Marginal Agreement Red: GTV Other colors: HR GTV volumes RPS 1:RUQ DD LPS Marginal agreement along liver 4 contours include entire liver surface in contact with tumor, 3 contours exclude liver

16. Conclusion Overall agreement for HR GTV boost volumes was moderate Contour agreement was best: –Postero-laterally, abutting chest wall –Medially, abutting RP musculature, ipsilateral para-vertebral space, great vessels Contour agreement most variable: –Abutting organs such as liver and bladder –Discrepancies are explained by differing surgical opinions regarding partial organ resections for these cases –Highlights extreme importance of collaboration between radiation and surgical oncologist for each patient

17. Future Directions Further discussion among sarcoma radiation and surgical oncologists is needed to reach improved consensus An atlas with detailed examples of HR GTV volumes may be an effective educational tool