Abstract
BACKGROUND: The cornerstone of the treatment of malignant peripheral nerve sheath tumors (MPNST) is surgical resection. Radiation and chemotherapy are variably employed. The optimal treatment remains uncertain, particularly for unresectable or metastatic disease and patients with neurofibromatosis type-1 (NF-1). METHODS: We present data for fifty-eight patients with newly diagnosed MPNST enrolled on the Children's Oncology Group study ARST0332. Patients were treated with risk-adapted therapy including surgery with or without radiotherapy and ifosfamide and doxorubicin chemotherapy. RESULTS: Most patients had primary tumors that were greater than 5 cm (86%), deep (95%), and invasive (74%), and 10% had distant metastases. Thirty-two (55%) patients had germline NF-1 and 26 (45%) did not. Thirty-one patients received neoadjuvant therapy and 22 were evaluable for response with 5 (23%) attaining an objective response, 10 (45%) stable disease, and 7 (32%) progressive disease. Estimated 5-year event-free survival (EFS) was 87%, 52% and 0% for the low- (n = 8), intermediate- (n = 44) and high-risk (n = 6) patients, respectively. In univariate analysis, EFS and overall survival (OS) differed by sex, presence or absence of metastatic disease, risk group, and achievement of upfront or delayed R0/R1. There was no difference in EFS or OS based on germline NF-1 status. CONCLUSION: The treatment strategy in ARST0332 achieved excellent outcomes for low-risk MPNST. Patients with high risk (metastatic) MPNST have poor outcomes and novel treatments are needed. (NCT00346164).