Real-world outcomes of neoadjuvant concurrent chemoradiotherapy with epirubicin–ifosfamide in localized high-grade soft tissue sarcoma: A single-center retrospective series (N=57).

e23547 Background: Neoadjuvant chemotherapy combined with radiotherapy (nCRT) is an established strategy for selected patients (pts) with localized high-risk soft tissue sarcoma (STS). However, real-world data on this concurrent multimodal approach remain limited. We evaluated clinicopathologic characteristics and outcomes in high-risk localized STS pts treated with nCRT using the regimen reported by Gronchi et al. (JCO 2012). Methods: We conducted a retrospective single-center study of consecutive pts with localized high-grade STS treated with nCRT at Hospital Gregorio Marañon (2014-2024). Treatment (Tx) was 3 cycles of epirubicin-ifosfamide concurrent with RT. Clinical and treatment variables, toxicity, RECIST 1.1 response, and recurrence patterns were analyzed. Primary outcomes included R0 resection and pathologic response; secondary outcomes were local control, DFS and OS. Results: Fifty-seven pts were included (M 31/F 26), median age of 51 years (21-70), 93.0% had tumors >5 cm. Primary sites were extremities (84.2%), head/neck (5.3%), and other non-retroperitoneal sites (10.5%). Most common histologies were undifferentiated pleomorphic sarcoma (19.3%), liposarcoma (17.5%), undifferentiated sarcoma NOS (15.8%), synovial sarcoma (14.0%), and malignant peripheral nerve sheath tumor (10.5%). Neoadjuvant treatment was completed in 94.7% (3 discontinuations due to toxicity). Grade 3–4 chemo-related adverse events (AEs) occurred in 56.1%, mainly hematologic. RT (50 Gy/25 fx) was delivered in 87.7%; grade 3–4 RT-related AEs occurred in 12.3%, with discontinuation in 10.5%. By RECIST 1.1, partial response was 49.1%, stable disease 24.6%, and complete response 3.5%. Definitive surgery was performed in 93.0%, with an R0 rate of 86.8%. Major pathologic response (>90% necrosis) was 22.6%. Intraoperative RT was delivered in 81.1%. Postoperative grade ≥3 acute and late complications occurred in 15% and 34%, mostly infections (7.5%, 13.2%) and wound-healing disorders (9.4%, 11.3%). After a median follow-up of 38 months, 45.3% relapsed, mainly distant (41.5% vs 13.2% local). The median progression-free survival and recurrence-free survival were 28.45 and 24.73 months, respectively. Four-year overall survival (OS) was 79% (95% CI 63-95). No significant OS differences were observed by margins (R0 vs R1), tumor size (<5, 5–10, >10 cm), necrosis (≥90% vs <90%), or complications in univariate or multivariate analysis, likely due to small sample size and cohort heterogeneity. Conclusions: In this real-world retrospective cohort of localized high-grade STS, epirubicin-ifosfamide-based nCRT was feasible and associated with encouraging surgical and disease-control outcomes. These data support prospective evaluation and may help refine patient selection for intensified multimodality tx strategies.