P11.44.a the role of radiotherapy in malignant peripheral nerve sheath tumors: a multicenter cohort study

BACKGROUND Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are rare and aggressive malignant soft-tissue sarcomas (STS), of which 40% are associated with neurofibromatosis type 1 (NF1). Current treatment in localized disease mainly revolves around surgical excision, yet MPNSTs harbor a high probability of local recurrence (LR). Radiotherapy (RT) is increasingly being used, as it improves local control in STS, yet does not impact survival. Nevertheless, its use is controversial in some cases as major wound complications can be much higher and NF1 patients harbor a potential higher risk for secondary malignancies as MPNST commonly arise within plexiform neurofibromas. This study evaluates the use of RT in these rare tumors and tries to understand its impact in local control, especially in the NF1 setting. MATERIAL AND METHODS Surgically treated primary MPNSTs between 1988 to 2019 in the MONACO multicenter cohort were included. Demographic and treatment differences, especially the use of RT, between NF1 and non-NF1 were analyzed. Univariate and multivariable logistic regression analyses were used to identify factors independently associated with the use of radiotherapy. Multivariate Cox regression analyses were performed to identify factors associated with LR in NF1 patients. RESULTS A total of 528 patients (31.8% NF1) were included, of which 149 (28.2%) developed a LR. RT was administered in 53.2% of patients (55.6% in NF1). Of these, 26.7% received neoadjuvant RT, and 71.2% adjuvant RT. The use of both treatment modalities was similar between patients with and without NF1. Multivariable regression showed that microscopically positive margins and high-grade tumors were independent factors for the use of RT. The rate of RT use in NF1 did not alter after correcting for tumor-, patient- and surgical factors. RT did not impact overall survival in sporadic and NF1 associated MPNST. In NF1 patients, microscopically positive margins (R1) (HR 3.2; 95% CI, 1.41-7.62), tumor size >5cm (HR 2.2; 95% CI, 1.14-4.3), and a high grade (HR 3.13; 95% CI, 1.23-7.98) were independent risk factors for the development of a LR. Correcting for tumor-, patient- and surgical factors, use of RT was not associated lower rates of LR, in contrast to the sporadic population. CONCLUSION Radiotherapy is commonly used in MPNST treatment regardless of its origin in NF1. While it may impact LR rate in sporadic patients, this is less clear in NF1 patients. Further studies are needed to evaluate its role and indications in NF1 associated MPNST.