Simple Summary:& nbsp;Around 40% of patients with MPNSTs develop distant metastasis (DM) within five years. Identification of MPNST patients more likely to develop DM and the identification of... Show moreSimple Summary:& nbsp;Around 40% of patients with MPNSTs develop distant metastasis (DM) within five years. Identification of MPNST patients more likely to develop DM and the identification of prognostic factors after DM diagnosis may guide clinical decision-making and may result in a better balance between quantity and quality of life. This study aimed to identify clinicopathologic and treatment-related factors associated with the development of DM and with overall survival (OS) after DM diagnosis. NF1, high grade, tumor size, triton and R2 resections were independent risk factors for the development of DM. This is the first study that reveals that NF1 status is also independently associated with worse survival after DM diagnosis with a median survival difference of more than 6 months between NF1 and no-NF1 patients.Purpose: This multicenter cohort study aimed to identify clinicopathologic and treatment-related factors associated with the development of distant metastasis (DM) and with overall survival (OS) after DM diagnosis in patients with malignant peripheral nerve sheath tumors (MPNST). Methods: All patients diagnosed with primary MPNST from 1988 to 2019 who were surgically treated for the primary tumor were included. Multivariable Cox regression analyses were performed to identify factors associated with DM and OS after DM diagnosis. Results: A total of 383 patients were included in this analysis, of which 150 developed metastatic disease. No differences in clinicopathologic characteristics and clinical outcome were found between patients with synchronous and metachronous DM. Neurofibromatosis type 1 (NF1), high grade, tumor size, triton and R2 resections were independent risk factors for the development of DM. NF1 and more than two metastasis sites were independently associated with worse OS after DM diagnosis. Metastasectomy, chemotherapy and the metastatic site category 'other' were associated with prolonged survival after DM diagnosis. Conclusions: This analysis provides important insights into clinicopathologic and treatment factors associated with outcomes in metastatic MPNST. Moreover, NF1-status is associated with a higher risk of DM; it is also independently associated with worse survival in metastatic MPNST. Show less
