Effect of MYCN Amplification on Tumor Response and Recurrence in Patients With Stage IV Neuroblastoma

Abstract

PURPOSE – MYCN amplification (MYCN-A) is an important prognostic marker in neuroblastoma. However, the impact of MYCN-A in patients with metastasized high-risk neuroblastoma during the course of disease remains unclear. The aim of this study was to investigate response and relapse patterns of stage IV patients with and without amplification of MYCN.MATERIALS AND METHODS – Amplification of the MYCN oncogene was assessed by fluorescence in situ hybridization, whole exome sequencing, or single nucleotide polymorphism analysis. Complete remission (according to the revised International Neuroblastoma Response Criteria) and survival outcomes were estimated.RESULTS – Among the 164 patients older than 12 months with metastatic high-risk neuroblastoma, 50 (30%) had MYCN-A. MYCN-A was a significant prognostic marker for overall survival (P =.04). Patients with MYCN-amplified tumors reached complete remission faster compared with those without MYCN amplification (HR, 1.8 [95% CI, 1.2 to 2.8]; P <.01). MYCN-A was associated with recurrence when evaluated from diagnosis and after induction treatment (HR, 1.6 [95% CI, 1.0 to 2.4]; and HR, 1.8 [95% CI, 1.1 to 2.8], respectively), as well as to the cumulative incidence of recurrence (P =.04 and P =.03, respectively). SIOPEN scores detected on meta-[123I]iodobenzylguanidine (MIBG) scintigraphy were significantly lower in patients with MYCN-amplified tumors than in patients with MYCN nonamplified tumors at diagnosis and after induction treatment (P <.01 and P =.01, respectively). From end of induction, MYCN-A stratified by SIOPEN score was associated with the cumulative incidence of recurrence (P <.01).CONCLUSION – Despite achieving complete remission faster, patients with MYCN-A have a higher probability of recurrence compared with those without MYCN-A.