title: Striking dichotomy in outcome of MYCN-amplified neuroblastoma in the contemporary era.
abstract: BACKGROUND
  The authors exploited a large database to investigate the outcomes of patients with high-risk neuroblastoma in the contemporary era.
  
  
  METHODS
  All patients with high-risk neuroblastoma aged <12 years who were treated during induction at the authors' institution from 2000 through 2011 were studied, including 118 patients with MYCN-amplified [MYCN(+)] disease and 127 patients aged >18 months with MYCN-nonamplified [MYCN(-)] stage 4 disease.
  
  
  RESULTS
  A complete response/very good partial response (CR/VGPR) to induction was correlated with significantly superior event-free survival (EFS) (P < .001) and overall survival (OS) (P < .001) compared with a partial response or less. Patients with MYCN(+) and MYCN(-) disease had similar rates of CR/VGPR to induction (P = .366), and those with MYCN(+) and MYCN(-) disease who attained a CR/VGPR had similar EFS (P = .346) and OS (P = .542). In contrast, only MYCN(+) patients had progressive disease as a response to induction (P < .001), and early death from progressive disease (<366 days after diagnosis) was significantly more common (P < .001) among those with MYCN(+) disease. Overall, among patients who had a partial response or less, MYCN(+) patients had significantly inferior EFS (P < .001) and OS (P < .001) compared with MYCN(-) patients, which accounted for the significantly worse EFS (P = .008) and OS (P = .002) for the entire MYCN(+) cohort versus the MYCN(-) cohort.
  
  
  CONCLUSIONS
  Patients with MYCN(-), high-risk neuroblastoma display a broad, continuous spectrum with regard to response and outcome, whereas MYCN(+) patients either have an excellent response to induction associated with good long-term outcome or develop early progressive disease with a poor outcome. This extreme dichotomy in the clinical course of MYCN(+) patients points to underlying biologic differences with MYCN(+) neuroblastoma, the elucidation of which may have far-reaching implications, including improved risk classification at diagnosis and the identification of targets for treatment.
authors.affiliation: Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors.forename: Brian H
authors.initials: BH
authors.lastname: Kushner
authors.forename: Shakeel
authors.initials: S
authors.lastname: Modak
authors.forename: Kim
authors.initials: K
authors.lastname: Kramer
authors.forename: Michael P
authors.initials: MP
authors.lastname: LaQuaglia
authors.forename: Karima
authors.initials: K
authors.lastname: Yataghene
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Basu
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Roberts
authors.forename: Nai-Kong V
authors.initials: NK
authors.lastname: Cheung
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D016208:Databases, Factual; D018572:Disease-Free Survival; D005260:Female; D005784:Gene Amplification; D006801:Humans; D060828:Induction Chemotherapy; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D000071447:N-Myc Proto-Oncogene Protein; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins
keywords: MYCN; contemporary therapy; induction; neuroblastoma