11570 Background: Malignant peripheral nerve sheath tumors (MPNST) are rare, aggressive soft-tissue sarcomas frequently associated with neurofibromatosis type 1 (NF1). Prospective trials are scarce, and prognostic factors and treatment effects remain incompletely defined. Methods: We conducted a retrospective observational cohort study of 200 patients (215 tumor episodes) with histologically confirmed MPNST treated at a national sarcoma referral center between 2000 and 2025. Overall survival (OS) and progression-free survival (PFS) were estimated via Kaplan–Meier methods. Multivariable Cox models with multiple imputation (MICE, m=40) were adjusted for clinical factors. Restricted mean survival time (RMST) at 5 years quantified absolute survival differences. Interaction analyses assessed heterogeneity of radiotherapy (RT) effects. Results: Median age was 40 years; 51. 5% of patients had NF1. Median OS and PFS were 74. 6 and 9. 1 months, respectively. NF1-associated MPNST had significantly shorter OS (28. 5 vs 141. 0m; p=0. 012), with a 5-year RMST reduction of 8. 5 months (95% CI -15. 0 to -2. 3; p=0. 01). In the multivariable Cox model with multiple imputation, advanced stage (HR 2. 28; 95% CI 1. 68–3. 09; p 60 days in 28. 4%. A significant interaction was observed between RT and surgical margins (pᵢnt=0. 028): RT markedly improved OS in R1/R2 resections (HR 0. 31, 95% CI 0. 16–0. 61) and in locally advanced disease, but not after R0 resection. In NF1 patients, imaging-detected tumors had better surgical margins and lower risk of synchronous metastasis despite similar tumor size. Conclusions: MPNST outcomes remain poor, particularly in NF1. Radiotherapy confers a clear survival benefit in high-risk surgical contexts. Optimizing diagnostic pathways, especially in NF1 patients, may improve outcomes. Survival Predictors (Multivariable OS) Hazard Ratio (95% CI) p-value Stage 2. 28 (1. 68–3. 09) <0. 001 FNCLCC Grade 1. 95 (1. 39–2. 75) <0. 001 NF1-associated 1. 67 (1. 11–2. 51) 0. 014 Central Location 1. 63 (1. 02–2. 60) 0. 041 Female Sex 0. 43 (0. 29–0. 66) <0. 001 RT Benefit in R1/R2 Resection 0. 31 (0. 16–0. 61) 0. 001
Coste et al. (Wed,) studied this question.