Malignant peripheral nerve sheath tumors: a report from Children's Oncology Group study ARST0332

The cornerstone of the treatment of malignant peripheral nerve sheath tumors 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).

We present data for 58 patients with newly diagnosed malignant peripheral nerve sheath tumors 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.

Most patients had primary tumors that were greater than 5 cm (86%), deep (95%), and invasive (74%), and 10% had distant metastases. Of the patients, 32 (55%) had germline NF-1, and 26 (45%) did not. Among patients, 31 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 was 87%, 52%, and 0% for the low- (n = 8), intermediate-, (n = 44), and high-risk (n = 6) patients, respectively. In univariate analysis, event-free survival and overall survival differed by sex, presence or absence of metastatic disease, risk group, and achievement of upfront or delayed R0 and/or R1. There was no difference in event-free survival or overall survival based on germline NF-1 status.

The treatment strategy in ARST0332 achieved excellent outcomes for low-risk malignant peripheral nerve sheath tumors. Patients with high-risk (metastatic) malignant peripheral nerve sheath tumors have poor outcomes, and novel treatments are needed (NCT00346164).