title: Oncologic outcomes of sporadic, neurofibromatosis-associated, and radiation-induced malignant peripheral nerve sheath tumors.
abstract: BACKGROUND
  Malignant peripheral nerve sheath tumors (MPNSTs) occur sporadically, after prior radiation therapy (RT), or in association with neurofibromatosis type 1 (NF1). It is controversial whether patients with NF1-associated MPNST have worse outcomes. We investigated the prognostic significance of sporadic, NF1-associated, and RT-induced MPNST.
  
  
  METHODS
  Patients with primary high-grade MPNST from 1982 to 2011 were identified from a prospectively maintained database. Patients with sporadic MPNST were included only if the MPNST was not associated with NF1 or a neurofibroma or if it was immunohistochemically S100-positive.
  
  
  RESULTS
  We studied 105 patients; 42 had NF1-associated tumors, 49 sporadic, and 14 RT-induced. Median age at diagnosis was 38 years. Median follow-up for surviving patients was 4 years. Mean tumor diameter was 5.5 cm for RT-induced tumors and 9.7 cm for NF1-associated and sporadic tumors (P=0.004). In multivariate analysis, factors associated with worse disease-specific survival (DSS) were larger size (HR 1.08; 95% CI 1.04-1.13; P<0.001) and positive margin (HR 3.30; 95% CI 1.74-6.28; P<0.001). Age, gender, site of disease, and S100 staining were not associated with DSS. The 3-year and median DSS were similar for NF1 and sporadic cases; combined 3-year DSS was 64% and median DSS was 8.0 years. For RT-induced tumors, 3-year DSS was 49% and median DSS was 2.4 years. The relationship between RT association and DSS approached statistical significance (HR 2.29; 95% CI 0.93-5.67; P=0.072).
  
  
  CONCLUSIONS
  Margin status and size remain the most important predictors of DSS in patients with MPNST. NF1-associated and sporadic MPNSTs may be associated with improved DSS compared with RT-induced tumors.
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: LaFemina
authors.forename: Li-Xuan
authors.initials: LX
authors.lastname: Qin
authors.forename: Nicole H
authors.initials: NH
authors.lastname: Moraco
authors.forename: Cristina R
authors.initials: CR
authors.lastname: Antonescu
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Fields
authors.forename: Aimee M
authors.initials: AM
authors.lastname: Crago
authors.forename: Murray F
authors.initials: MF
authors.lastname: Brennan
authors.forename: Samuel
authors.initials: S
authors.lastname: Singer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017024:Chemotherapy, Adjuvant; D016001:Confidence Intervals; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000209:etiology; D018365:Neoplasm, Residual; D009381:Neoplasms, Radiation-Induced / Q000473:pathology* / Q000628:therapy*; D018317:Nerve Sheath Neoplasms / Q000473:pathology* / Q000628:therapy*; D009456:Neurofibromatosis 1 / Q000473:pathology* / Q000628:therapy*; D016016:Proportional Hazards Models; D018714:Radiotherapy, Adjuvant; D012189:Retrospective Studies; D012307:Risk Factors; D018709:Statistics, Nonparametric; D015996:Survival Rate; D055815:Young Adult