Outcomes of malignant peripheral nerve sheath tumors in neurofibromatosis type 1 and sporadic patients: A 25-year experience from a sarcoma referral center.

Abstract

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<0.001), higher FNCLCC grade (HR 1.95; 95% CI 1.39–2.75; p<0.001), NF1 status (HR 1.67; 95% CI 1.11–2.51; p=0.014), central tumor location (HR 1.63; 95% CI 1.02–2.60; p=0.041), and increasing age (HR 1.04 per year; 95% CI 1.02–1.05; p<0.001) were independently associated with inferior OS, whereas female sex was strongly protective (HR 0.43; 95% CI 0.29–0.66; p<0.001). Major biopsy-surgery histologic discordance occurred in 21.6% of cases, and diagnostic delays > 60 days in 28.4%. A significant interaction was observed between RT and surgical margins (p_int=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