Neoadjuvant versus adjuvant chemotherapy for resectable high-grade soft tissue sarcoma: A real-world propensity-matched survival analysis.

11585 Background: High-grade soft tissue sarcomas are aggressive malignancies for which complete surgical resection remains the cornerstone of curative-intent therapy. Current clinical guidelines recommend consideration of perioperative chemotherapy for selected high-risk patients; however, the optimal timing of systemic therapy remains uncertain. We performed a real-world analysis to compare survival outcomes between neoadjuvant and adjuvant chemotherapy in patients with resected high-grade soft tissue sarcoma. Methods: We conducted a retrospective cohort study using the TriNetX Database, identifying adults (≥18 years) with high-grade soft tissue sarcoma who underwent surgical resection and received combination chemotherapy with doxorubicin and ifosfamide either within 6 months before surgery or after surgery . The index date was defined as time of diagnosis. Propensity score matching (1:1) was performed to balance baseline demographics and various comorbidities. Overall survival (OS) was assessed using Kaplan–Meier methods and Cox proportional hazards models at fixed time points (1, 3, 5, and 10 years) and over the entire follow-up period. Results: A total of 714 patients were identified (479 adjuvant; 235 neoadjuvant). After propensity score matching, 229 patients were included in each cohort. At 1 year, overall survival was similar between adjuvant and neoadjuvant chemotherapy (53.1% vs 53.1%; risk ratio RR 1.06, 95% CI 0.81–1.37; log-rank p = 0.77). Additionally, analyses at 3, 5, and 10 years demonstrated no statistically significant differences in OS between cohorts, with overlapping Kaplan–Meier survival curves at all evaluated time points. Over the entire follow-up period, survival probabilities at the end of follow-up were 51.5% in the adjuvant cohort and 53.4% in the neoadjuvant cohort. There was no significant difference in overall survival (hazard ratio HR 1.04, 95% CI 0.75–1.44; p = 0.73). Conclusions: In this large, real-world, propensity-matched analysis of patients with resectable high-grade soft tissue sarcoma, survival outcomes were comparable across short-, intermediate-, and long-term follow-up intervals in both neo-adjuvant and adjuvant chemotherapy cohorts. Current guidelines recommend neo-adjuvant radiation treatment as category 1, and chemotherapy (neo-adjuvant or adjuvant) is a consideration. Neo-adjuvant chemotherapy has the potential to delay definitive treatment, however, this analysis suggests that the timing of chemotherapy does not adversely impact the outcomes in short or long term follow up. There are several limitations to our analysis (size of the tumors and grading was not available and timing of XRT could not be assessed, however, given that AIM chemo cohort was selected, it can be assumed that patients had higher grade, larger tumors and received XRT as standard of care.