Radiation Exposure May Increase Risk of Malignant Peripheral Nerve Sheath Tumors in Neurofibromatosis: A Propensity-Matched Population-Level Analysis

INTRODUCTION: Neurofibromatosis type 1 (NF1) is a hereditary condition characterized by growth of neurofibromas, which can transform into aggressive malignant peripheral nerve sheath tumors (MPNSTs). We hypothesize MPNST onset may be increasingly susceptible in the setting of prior radiation exposure in NF1 patients. METHODS: We performed a population-level retrospective cohort study using data collected from the TriNetX Research Network, a multi-institutional database comprising 92 healthcare organizations. Patients with NF1 were identified using ICD-10 codes. The presence or absence of radiation procedural codes prior to MPNST onset determined the radiation exposure status. NF1 patients, with and without prior radiation exposure, were propensity score matched on age, sex, and significant comorbidities. MPNST incidence and median overall survival (OS) at 1, 3, and 5 years were assessed. Kaplan Meier curves were evaluated with log-rank tests and Cox Proportional-Hazards models. RESULTS: A total of 35,378 NF1 patients, including 884 radiation-exposed and 34,494 radiation-naive were identified. The incidence of MPNST was 24.55% in the radiation-exposed cohort compared to 1.00% in the radiation-naive cohort. Significant risk of MPNST onset was demonstrated in the setting of prior radiation history (Risk ratio, 19.64 [95% CI 10.79-35.73], p < 0.0001). After matching, rates of OS at 5 years were 43.89% and 71.73% for NF1 patients with and without radiation, respectively. Cox proportional hazards ratios (HR, 1.57 [95% CI, 1.04-2.42]) and log-rank tests (p = 0.031) showed significant mortality in the radiation-exposed NF1-MPNST group. CONCLUSIONS: Patients with NF1 who had prior radiation exposure had a significantly higher incidence of MPNST, as well as lower overall survival when compared to radiation-naive NF1 patients. This suggests that radiation in NF1 patients may be cautioned, and providers may consider different treatment paradigms in their NF1 patients to limit radiation exposure.