The Role of Radiotherapy in MPNST and the Impact of NF1 Status on Outcomes: Insights From A Multicenter Cohort Study.

Abstract

Background: Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are rare, aggressive sarcomas, with 40% associated with neurofibromatosis type 1 (NF1). Surgical excision is the main treatment for localized disease, however, local recurrence (LR) remains high. Radiotherapy (RTx) is increasingly used to enhance local control in STS, but its use remains controversial due to the potential for increased major wound complications and an increased risk of secondary malignancies in NF1 patients. This study investigated the use and impact of RTx on local control in MPNSTs, particularly in the NF1 setting.

Methods: Surgically treated primary MPNSTs from 1988 to 2019 in the MONACO multicenter cohort were included. Differences in demographics, treatment, and RTx use between NF1 and non-NF1 cases were examined. Factors influencing RTx administration and LR were assessed via multivariable analyses.

Results: Among 499 patients (33.1% NF1), 143 (28.7%) experienced LRs. Radiotherapy was administered to 56.3% of patients (57.0% in the NF1 group), with 27.3% receiving neoadjuvant and 72.7% adjuvant RTx. RTx was administered significantly more often to high-grade and extremity tumors. While RTx did not affect overall survival, it reduced LR risk in sporadic cases (HR 0.530; 95% CI 0.354-0.793) but not in the NF1 subgroup (HR 1.00; 95% CI 0.545-1.85). In NF1 patients, a microscopically positive margin (R1) was the only risk factor for LR development (HR 2.1; 95% CI, 1.19-3.79).

Conclusions: RTx is frequently used in the treatment of MPNSTs, regardless of NF1 status. While it may affect LR rate in sporadic cases, its impact in NF1 patients is less clear.