Striking dichotomy in outcome of MYCN-amplified neuroblastoma in the contemporary era

Cancer. 2014 Jul 1;120(13):2050-9. doi: 10.1002/cncr.28687. Epub 2014 Apr 1.

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.

Keywords: MYCN; contemporary therapy; induction; neuroblastoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Child
  • Child, Preschool
  • Databases, Factual
  • Disease-Free Survival
  • Female
  • Gene Amplification*
  • Humans
  • Induction Chemotherapy
  • Infant
  • Kaplan-Meier Estimate
  • Male
  • N-Myc Proto-Oncogene Protein
  • Neoplasm Staging
  • Neuroblastoma / drug therapy*
  • Neuroblastoma / genetics*
  • Neuroblastoma / mortality
  • Neuroblastoma / pathology
  • Nuclear Proteins / genetics*
  • Oncogene Proteins / genetics*
  • Prognosis
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Treatment Outcome

Substances

  • MYCN protein, human
  • N-Myc Proto-Oncogene Protein
  • Nuclear Proteins
  • Oncogene Proteins