Association of Histologic Subtype With Radiation Response and Survival Outcomes in Synovial Sarcoma

Jennifer K Matsui; Scott Jackson; Judy Fang; David G Mohler; Robert J Steffner; Raffi S Avedian; Gregory W Charville; Matt van de Rijn; Lynn Million; Alexander L Chin; Susan M Hiniker; Anusha Kalbasi; Everett J Moding

doi:10.1016/j.adro.2025.101718

Association of Histologic Subtype With Radiation Response and Survival Outcomes in Synovial Sarcoma

Adv Radiat Oncol. 2025 Jan 15;10(3):101718. doi: 10.1016/j.adro.2025.101718. eCollection 2025 Mar.

Authors

Affiliations

¹ The Ohio State University College of Medicine, Columbus, Ohio.
² Department of Radiation Oncology, Stanford University, Stanford, California.
³ Department of Orthopedic Surgery, Stanford University, Stanford, California.
⁴ Department of Pathology, Stanford University, Stanford, California.

Abstract

Purpose: Synovial sarcoma (SS) is a rare, aggressive soft tissue malignancy that is divided into biphasic and monophasic histologic subtypes. In addition to surgical resection, radiation therapy (RT) improves local control in patients at higher risk of recurrence. This study aimed to investigate the impact of histologic subtype on radiation response and survival outcomes in patients treated with RT as part of definitive management.

Methods and materials: We retrospectively identified patients with SS treated with RT and surgical resection from 1997 to 2020 at Stanford Medical Center. We assessed the association between histologic subtypes (biphasic vs monophasic) and response to preoperative RT based on imaging and pathology. Volumetric response was calculated using the pre-RT and post-RT/preoperative postcontrast T1-weighted magnetic resonance imaging images. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Univariable and multivariable analyses were conducted using Cox regression models. Variables for univariable and multivariable analyses included age, histologic subtypes, tumor location, tumor size, margin status, chemotherapy, and performance status.

Results: In our study, 50 patients met the inclusion criteria. The median age was 34.8 years at diagnosis, and 36% (n = 18) received concurrent chemotherapy. Biphasic (n = 18, 36%) and monophasic (n = 32, 64%) tumors exhibited significant differences in negative margin status (94% vs 66%, P = .036). Of the 22 patients who underwent preoperative RT, 15 patients had pre-RT and post-RT imaging to assess volumetric changes. Biphasic tumors demonstrated less necrosis at the time of surgical resection but a significantly greater volumetric decrease with preoperative RT (42% vs 5%, P = .004). PFS and OS were superior in biphasic tumors (P = .003 and P = .009, respectively). Multivariable analyses identified histologic subtypes (monophasic vs biphasic) as a significant factor impacting PFS (HR, 5.65; 95% CI, 1.78-17.91; P = .003).

Conclusions: Biphasic tumors exhibit an improved volumetric response to preoperative RT and improved outcomes. These findings underscore the importance of considering histology when tailoring treatment for patients with SS.