2001 CTOS Annual Meeting Posters— Biology

IMPACT OF SYT-SSX FUSION TYPE ON CLINICAL BEHAVIOR OF SYNOVIAL SARCOMA. A MULTI-INSTITUTIONAL STUDY OF 243 PATIENTS.
Marc Ladanyi¹,  Cristina R. Antonescu¹,  Murray F. Brennan¹,  Julia A. Bridge²,  Frederic G. Barr³,  Janet Shipley⁴,  Colin S. Cooper⁴,  Cyril Fisher⁴,  Björn Skytting⁵,  Olle Larsson^5
1Memorial Sloan-Kettering Cancer Center,  ²University of Nebraska Medical Center,  ³Hospital of the University of Pennsylvania,  ⁴Institute for Cancer Research and The Royal Marsden NHS Trust,  ⁵Stockholm Söder Hospital and Karolinska Hospital

METHODS: To address this issue more definitively, we collected data on SYT-SSX fusion type, pathology, and clinical course in a retrospective multi-institutional study of 243 patients (of whom 44% were under age 30 – age range 6-82) with synovial sarcoma, of which 89% were localized at presentation and 67% were extremity primaries.

RESULTS: SYT-SSX1 and SYT-SSX2 fusions were detected in 147 tumors (61%) and 91 tumors (37%), respectively. There were 180 (74%) monophasic and 61 (25%) biphasic tumors. The previously observed association of fusion type and histology was confirmed in this series (n=236; p<0.001). Of 236 cases with data for both fusion type and histologic type, there were only 3 SYT-SSX2+ biphasic tumors. There was also a statistically significant association of fusion type and patient sex (n=232; p=0.03); the male-female ratio of SYT-SSX1 cases was 1:1, whereas for SYT-SSX2 cases, it was close to 1:2. There was a trend for patients with SYT-SSX1 + tumors to present more often with metastatic disease (n=231; p=0.05). There was no significant association of fusion type with patient age and size or site (axial vs peripheral) of the primary tumor. Median and 5 year overall survivals for the SYT-SSX1 and SYT-SSX2 groups were 6.1 years and 53%, and 13.7 years and 73%, respectively. Overall survival was significantly better among SYT-SSX2+ cases (n=228; p=0.03), among cases localized at diagnosis (n=231; p<0.0001), and among patients with primary tumors less than 5 cm in greatest dimension (n=200; p=0.01). Age, sex, histologic type, and axial vs peripheral primary site had no impact on overall survival. The impact of fusion type on survival remained significant when stratified for primary tumor size (n=198; p=0.03) but was no longer significant when stratified for disease status at presentation (n=226; p= 0.16). Cox regression identified disease status (p<0.0001) and primary tumor size (p=0.04) as the only factors independently predictive of overall survival in the subset of 160 patients with information on all factors. Within the subset of patients with localized disease at diagnosis (n=202), the median and 5-year survival for the SYT-SSX1 and the SYT-SSX2 groups were 9.2 years and 61%, vs 13.7 years and 77%, respectively. Patients whose tumors contained the SYT-SSX2 fusion (n=202, p=0.08) or were smaller (n=174, p=0.12) showed a trend toward better survival by log rank test, whereas tumor histology had no impact (p=0.8). By Cox regression analysis considering all factors, SYT-SSX fusion type emerged as the only independent significant factor (p=0.044) for overall survival within the subset of 133 patients with localized disease at diagnosis who had information on all factors.

CONCLUSION: Overall, SYT-SSX fusion type appears to exert part of its impact on prognosis prior to presentation, through its association with stage at presentation, which remains the strongest prognostic factor in all patients.