Early recurrence and outcome determinants in NF1-associated malignant peripheral nerve sheath tumors: A single-center retrospective analysis.

Abstract

e23563 Background: Malignant peripheral nerve sheath tumors (MPNST) are rare but highly aggressive malignancies in patients with neurofibromatosis type 1 (NF1). Compared with sporadic MPNST, NF1-associated tumors are characterized by earlier onset, biological heterogeneity, and poor local disease control. Real-world data on recurrence patterns, metastatic disease, and prognostic factors in this population remain limited. Methods: We performed a retrospective single-center analysis of 12 adult patients with NF1-associated MPNST treated between 2022 and 2025. Clinical, pathological, and treatment-related variables were collected. Recurrence-free survival (RFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Associations between clinicopathologic factors and outcomes were assessed using non-parametric and exact statistical tests ( p < 0.05). Results: Median age was 36 years (Q1–Q3: 31.0–46.5). High-grade tumors accounted for 58.3% of cases. Distant metastases at diagnosis were present in 25.0%. Median tumor size was 10.5 cm (Q1–Q3: 6.35–13.25). A high rate of early recurrence was observed, with 58.3% of patients developing relapse. Median RFS was 15 months (95% CI: 4–22), and recurrence risk increased from 20.5% at 5 months to 81.8% at 20 months, indicating early postoperative disease failure. Metastatic status was strongly associated with mortality: 100% of deaths occurred in patients with distant metastases ( p = 0.045). Recurrence occurred exclusively in patients without metastases, reflecting competing-risk dynamics in this small cohort. No significant associations were identified between recurrence and tumor size, grade, resection margins, chemotherapy, or tumor localization. A non-significant trend toward an association between higher grade and positive resection margins was observed ( p = 0.076). Median OS was not reached; estimated 5-year OS was 82.5% (95% CI: 46.1–95.3). Conclusions: NF1-associated MPNST is characterized by a high risk of early postoperative recurrence, representing a major clinical challenge. Metastatic disease emerged as the clearest determinant of mortality, while conventional clinicopathologic factors showed limited prognostic value. These findings highlight the need for larger NF1-MPNST cohorts and direct comparison with sporadic MPNST to better define biological differences, refine risk stratification, and guide translational and surveillance strategies.