Effect of <i>MYCN</i> Amplification on Tumor Response and Recurrence in Patients With Stage IV Neuroblastoma.

Abstract

<i>MYCN</i> amplification (<i>MYCN</i>-A) is an important prognostic marker in neuroblastoma. However, the impact of <i>MYCN</i>-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 <i>MYCN</i>. Amplification of the <i>MYCN</i> 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. Among the 164 patients older than 12 months with metastatic high-risk neuroblastoma, 50 (30%) had <i>MYCN</i>-A. <i>MYCN</i>-A was a significant prognostic marker for overall survival (<i>P</i> = .04). Patients with <i>MYCN</i>-amplified tumors reached complete remission faster compared with those without <i>MYCN</i> amplification (HR, 1.8 [95% CI, 1.2 to 2.8]; <i>P</i> < .01). <i>MYCN</i>-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 (<i>P</i> = .04 and <i>P</i> = .03, respectively). SIOPEN scores detected on <i>meta</i>-[¹²³I]iodobenzylguanidine (MIBG) scintigraphy were significantly lower in patients with <i>MYCN</i>-amplified tumors than in patients with <i>MYCN</i> nonamplified tumors at diagnosis and after induction treatment (<i>P</i> < .01 and <i>P</i> = .01, respectively). From end of induction, <i>MYCN</i>-A stratified by SIOPEN score was associated with the cumulative incidence of recurrence (<i>P</i> < .01). Despite achieving complete remission faster, patients with <i>MYCN</i>-A have a higher probability of recurrence compared with those without <i>MYCN</i>-A.