A multi-center retrospective outcomes analysis of patients with localized synovial sarcoma.
Authors: Stefano Testa, Maggie Yuxi Zhou, Brian Schulte, Victoria Wang, Katie Kenny, Austine Peng, Anupam M. Desai, Bruno Bockorny, Ali Baghian, Daniel R. Schmidt, Ross Alan Okimoto, Nam Bui, Minggui Pan, Kristen N. Ganjoo, Varun Monga
Journal: Journal of Clinical Oncology (2025)

e23555 Background: Synovial sarcoma (SS) is a rare and aggressive form of soft tissue sarcoma which disproportionately affects younger individuals. Optimal treatment for localized disease is unclear. Utilization of perioperative systemic therapy as well as radiation can frequently vary between centers. Here we aim to elucidate associations between multimodality treatment and pt outcomes. Methods: We reviewed 264 pts diagnosed with SS at three sarcoma centers between 2000 and 2024. Demographic data, disease features, and treatment modalities were analyzed by Cox proportional hazard (PH) analysis with the outcomes of OS and DFS. Results: The cohort included 134 males (51%), and 130 females (49%). The most common ethnicities were Caucasian (n = 169, 64%), Hispanic (n = 24, 9%), Asian American and Pacific Islander (n = 34, 13%), and African-American (n = 21, 8%). Median age at diagnosis was 35 yrs (range 6-81 yrs). 56% of the pts had a monophasic SS (n = 150, 56%), deep tumor location with invasion of the fascia (n = 116, 44%), and median tumor diameter of 6 cm (range 1.0-31.0 cm). Tumors arose mostly in the trunk, extremities or chest wall (n = 240, 90%). Neoadjuvant chemotherapy was administered to 100 (38%) pts, with 63 (24%) also receiving neoadjuvant radiation. The most common regimen was Adriamycin-Ifosfamide-Mesna (AIM, n = 87, 33%), with median number of cycles being 3 (range 1-6). External beam radiation therapy (EBRT) was the most common neoadjuvant radiotherapy (n = 59, 22%), and it was administered with chemotherapy in 42 pts (26%). 105 pts (40%) received adjuvant chemotherapy with 48 (17%) also receiving adjuvant radiation. AIM was the most common adjuvant regimen (n = 95, 36%). All pts underwent surgical resection, mostly showing a R0 resection (n = 166, 63%). Multivariate Cox PH analysis showed worse OS for pts with lung nodules ≥ 1 cm at diagnosis (p &lt; 10 -3 ), those with macroscopic residual tumor at the resection margins (p = 0.0002), and pts with larger tumors (p &lt; 10 -3 ). Single-agent neoadjuvant ifosfamide or doxorubicin correlated with worse OS (p = 0.01, p = 0.04), while neoadjuvant EBRT correlated with better OS (p = 0.02). Adjuvant or neoadjuvant combination chemotherapy (AIM) did not correlate with OS (p = 0.76, p = 0.49). Neoadjuvant ifosfamide single-agent (p = 0.002), and larger tumor size (p = 0.0005) correlated with worse DFS. Conclusions: Our findings indicate that tumor size, margin status, and presence of lung nodules at diagnosis are independent risk factors for poor DFS and OS in pts with SS. Neoadjuvant or adjuvant AIM did not improve outcomes and pts receiving single-agent chemotherapy fared worse, suggesting the importance of multi-drug regimens, though our data may suffer from such biases as confounding by indication. These results also indicate that EBRT should be considered for pts with localized SS. Future research is needed to better define outcomes for pts with SS receiving multimodality therapy, prospectively.