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

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. Cancer 2014;120:2050–2059 . © 2014 American Cancer Society .