Comprehensive evaluation of context dependence of the prognostic impact of MYCN amplification in neuroblastoma: A report from the International Neuroblastoma Risk Group (INRG) project

Abstract

Background MYCN amplification (MYCN‐A) is an established adverse prognostic factor in neuroblastoma. The extent to which the prognostic impact of MYCN‐A depends on other factors has not been fully characterized. Patients and methods Using the International Neuroblastoma Risk Group database, we constructed Cox models of overall survival (OS) to obtain hazard ratios of the effect of MYCN‐A within subgroups defined by other prognostic factors. Cox models assessed the degree to which the prognostic impact of MYCN‐A was modulated by each other covariate. We used absolute hazard ratio (HR) differences to construct classification trees to identify subgroups with greatest differential prognostic effect of MYCN‐A. Results In a cohort of 6223 patients with known MYCN status, the OS hazard ratio associated with MYCN‐A was 6.3 (95% confidence interval 5.7‐7.0, P < .001). Age at diagnosis conferred the largest HR absolute difference for MYCN‐A between subgroups (HR absolute difference 16.6; HRs for MYCN‐A of 19.6 for most impacted by MYCN status were those who were MYCN status cannot be assessed. Subgroups where MYCN‐A has large effect may be prioritized for agents targeting Myc family proteins.