222 - Outcomes from Phase 2 Trial of Preoperative Image Guided Intensity Modulated Photon Radiation Therapy (IMRT) with Simultaneously Integrated Boost (SIB) to the High-Risk Margin for Retroperitoneal Sarcomas (RPS)

03:10pm - 03:20pm ET

Room 205

Presenter(s)

Kevin Liu, MD, DPhil - Brigham and Womens Hospital, Boston, MA

K. X. Liu¹, Y. L. Chen², B. Y. Yeap³, A. O. Naghavi⁴, Y. J. Hitchcock⁵, K. E. Salerno^6,7, J. M. Kane⁸, M. L. Rose⁹, S. Cohen¹⁰, D. G. Kirsch^11,12, D. G. Blazer¹³, J. M. Michalski¹⁴, I. A. Petersen¹⁵, A. J. Bishop¹⁶, D. J. Konieczkowski¹⁷, D. Wang¹⁸, E. Choy¹⁹, G. P. Nielsen²⁰, J. T. Mullen²¹, and T. F. DeLaney^22,23; ¹Department of Radiation Oncology, Mass General Brigham, Boston, MA, ²Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, ³Department of Biostatistics, Massachusetts General Hospital and Harvard Medical School, Boston, MA, ⁴H. Lee Moffitt Cancer Center and Research Institute, Department of Radiation Oncology, Tampa, FL, ⁵Department of Radiation Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, ⁶Center for Cancer Research, National Cancer Institute, Bethesda, MD, ⁷Roswell Park Comprehensive Cancer Center, Buffalo, NY, ⁸Department of Surgery, Roswell Park Cancer Institute, Buffalo, MA, ⁹Department of Radiation Oncology, Mass General Brigham, Harvard Medical School, Boston, MA, ¹⁰Massachusetts General Hospital, Boston, MA, ¹¹University of Toronto, Toronto, ON, Canada, ¹²Duke University Medical Center, Department of Radiation Oncology, Durham, NC, ¹³Duke University Medical Center, Durham, NC, ¹⁴Washington University School of Medicine, St. Louis, MO, ¹⁵Department of Radiation Oncology, Mayo Clinic, Rochester, MN, ¹⁶Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, ¹⁷Department of Radiation Oncology, James Cancer Hospital/Wexner Medical Center, The Ohio State University, Columbus, OH, ¹⁸Rush University Medical Center, Chicago, IL, ¹⁹Division of Hematology-Oncology, Massachusetts General Hospital, Boston, MA, ²⁰Department of Pathology, Massachusetts General Hospital, Boston, MA, ²¹Department of Surgery, Dartmouth Cancer Center, Lebanon, NH, ²²Dartmouth Geisel School of Medicine, Harvard Medical School, Boston, MA, ²³Dartmouth-Hitchcock Medical Center, Lebanon, NH

Purpose/Objective(s): Despite aggressive surgeries, patients (pts) with RPS experience high rates of local recurrence (approximately 35-50%), with the highest risk at the posterior margin. The risk of local recurrence may be reduced with the addition of preoperative RT in select pts. However, there are limited data on whether higher doses may further improve local control. Thus, we conducted a multi-institutional, prospective Phase II study to investigate whether preoperative IMRT with selective dose escalation to the posterior RPS margin (clinical target volume [CTV]2) can decrease local recurrence and is tolerable.

Materials/Methods:

Pts >18 years at diagnosis with pathologic confirmation of primary RPS were enrolled from November 2018 to September 2023. Using image-guided photon IMRT, pts received 50.4 Gy in 28 fractions to CTV1 (tumor and adjacent tissue at risk of subclinical disease) with SIB to CTV2 to 63.0 Gy in 28 fractions. Pts had restaging and surgery 4-8 weeks after completion of RT. Primary objective was cumulative incidence of local progression (CILP) after the start of RT, with death as a competing risk. Secondary endpoints included surgical margin status, disease-free survival (DFS) and overall survival (OS). Toxicity was graded using CTCAE v4 and late toxicities were defined as any toxicity occurring >3 months after surgery.

Results: Of the 60 pts enrolled, 45 had liposarcoma (LPS) (25 with de-differentiated LPS and 12 with well-differentiated LPS), 6 leiomyosarcoma, and 9 other histologies. One patient passed away from disease progression before starting RT and was excluded from further analysis. Of the 5 pts who received RT and did not undergo surgery, 3 had metastases on post-RT and pre-operative imaging, 1 had local progression, and 1 declined surgery. Of the 54 pts who underwent resection, 33 had negative margins, 19 had positive margins and 2 had gross residual disease. With a median follow-up of 37.8 months (range: 1.4-73.4), 3-year CILP, DFS, and OS were 12.9%, 59.5%, and 81.8%, respectively. Of the 10 pts with local or marginal progression, 3 had local progression after 36 months (36.4, 37.1, and 66.0 months). Surgical Clavien-Dindo morbidity scores were 0(19), 1(21), 2(10), 3a (2), 3b(1), 4a(0), 4b(1), 5(0). No pts died due to surgical complications or other complications attributed to RT. Nine pts had late RT-associated grade =3 toxicities including weight loss (n=2), abdominopelvic pain (n=1), bladder perforation (n=1), chronic kidney disease (n=1), fatigue (n=1), lymphopenia (n=1), myelodysplastic syndrome (n=1), and neutropenia (n=1).

Conclusion: In pts with RPS, preoperative IMRT with dose escalation to 63.0 Gy to the high-risk posterior margin leads to a low rate of local progression of 12.9% at 3 years with encouraging DFS and OS. This approach appears to be well-tolerated without excessive peri-operative and long-term toxicities. Longer follow-up is important as late recurrences and toxicities can occur.