Background: Malignant peripheral nerve sheath tumors (MPNST) are rare tumors of childhood. The role of standard chemotherapy in unresectable MPNST is still unclear. We report the outcome and prognostic factors in the EpSSG risk‐adapted prospective study for localized pediatric MPNST.Methods: Patients were stratified into four treatment groups defined by surgical resection, tumor size, and tumor grade (G): (a) surgery‐only group—resected tumors G1; (b) adjuvant radiotherapy group—R0/R1, G2 tumors; (c) adjuvant chemotherapy group—R0/R1, G3 tumors; and (d) neoadjuvant chemotherapy group—R2 resected tumors and/or nodal involvement. Chemotherapy consisted of four courses of ifosfamide‐doxorubicin and two courses of ifosfamide concomitant with radiotherapy (50.4‐54 Gy).Results: Overall, the study included 51 patients. The 5‐year event‐free survival (EFS) and overall survival (OS) were 52.9% (95% confidence interval, 38.1‐65.8) and 62.1% (46.7‐74.3), respectively. The 5‐year EFS was 92% (56.6‐98.9) for treatment group 1 (N = 13), 33% (0.9‐77.4) for treatment group 2 (N = 4), 29% (4.1‐61.2) for treatment group 3 (N = 7), and 42% (23.1‐60.1) for treatment group 4 (N = 27). Response rate to chemotherapy (partial response + complete response) in patients with measurable disease was 46%. The presence of neurofibromatosis type 1 (NF1; 51% of patients) was an independent poor prognostic factor for OS and EFS.Conclusion: The outcome for patients with resectable MPNST was excellent. Standard ifosfamide‐doxorubicin for unresectable MPNST rendered the best reported outcome. Children with NF1 disease seem to have worse prognosis.

PURPOSE: Outcome for patients with metastatic rhabdomyosarcoma (RMS) is poor. This study presents the results of the MTS 2008 study with a pooled analysis including patients from the concurrent BERNIE study. PATIENTS AND METHODS: In MTS 2008, patients with metastatic RMS received four cycles of ifosfamide, vincristine, and actinomycin D (IVA) plus doxorubicin, five cycles of IVA, and 12 cycles of maintenance chemotherapy (low-dose cyclophosphamide and vinorelbine). The BERNIE study randomly assigned patients to the addition or not of bevacizumab to the same chemotherapy. Local therapy (surgery/radiotherapy) was given to the primary tumor and all metastatic sites when feasible. RESULTS: MTS 2008 included 270 patients (median age, 9.6 years; range, 0.07-20.8 years). With a median follow-up of 50.3 months, 3-year event-free survival (EFS) and overall survival (OS) were 34.9% (95% CI, 29.1 to 40.8) and 47.9% (95% CI, 41.6 to 53.9), respectively. In pooled analyses on 372 patients with a median follow-up of 55.2 months, 3-year EFS and OS were 35.5% (95% CI, 30.4 to 40.6) and 49.3% (95% CI, 43.9 to 54.5), respectively. Patients with ≤ 2 Oberlin risk factors (ORFs) had better outcome than those with ≥ 3 ORFs: 3-year EFS was 46.1% versus 12.5% ( P < .0001) and 3-year OS 60.0% versus 26.0% ( P < .0001). Induction chemotherapy and maintenance appeared tolerable; however, about two third of patients needed dose adjustments during maintenance. CONCLUSION: Outcome remains poor for patients with metastatic RMS and multiple ORFs. Because of the design of the studies, it was not possible to determine whether the intensive induction regimen and/or the addition of maintenance treatment resulted in apparent improvement of outcome compared with historical cohorts. Further studies, with novel treatment approaches are urgently needed, to improve outcome for the group of patients with adverse prognostic factors.