Factors contributing to recurrence in soft tissue sarcomas treated with peri-operative radiation

Introduction: Soft tissue sarcomas (STSs) are heterogeneous tumors requiring multidisciplinary care, with management often limited by distant recurrences (DRs). We aim to identify recurrence risk factors in patients treated definitively with radiation (RT) and surgery. Materials and methods: Patients with localized STS who completed pre- or post-operative RT were retrospectively evaluated. Tumor size, grade, necrosis, margin status, and chemotherapy were documented. Cox proportional hazards models evaluated recurrence risk factors separately for pre- and post-operative RT patients. The primary endpoint was recurrence: local recurrence (LR), DR, and recurrence-related death. Results: Between 2008 and 2024, 59 patients received pre-operative RT and 55 received post-operative RT. In pre-operative patients, mean age was 56.5 years, mean tumor size was 12.0 cm, 57.6% were grade 3, and 50.8% received chemotherapy. At 20.2-month median follow-up, there were 16 DR-only, 1 LR-only, 4 both DR/LR, and 3 recurrence-related deaths. Grade 3 trended toward a 3.5 times higher risk of recurrence versus grades 1–2 ( p = 0.07). In post-operative patients, mean age was 53.7 years, mean tumor size 10.0 cm, 58.1% were grade 3, and 16.4% received chemotherapy. At 21.2-month median follow-up, there were 12 DR-only, 4 LR-only, 8 both DR/LR, and 4 recurrence-related deaths. Large tumor size was significantly associated with recurrence (adjusted hazard ratio (aHR) 1.07, 95% confidence interval (CI) 1.0–1.14, p = 0.03), while grade 3 trended toward recurrence (aHR 2.70, 95% CI 0.9–8.17, p = 0.08). Conclusions: Most STS recurrences are distant, regardless of RT timing. Grade 3 trends toward recurrence in both groups, while large tumor size is associated with recurrence after post-operative RT. These factors may inform patient selection for future immunotherapy studies.