Genetic Alterations and Resectability Predict Outcome in Patients with Neuroblastoma Assigned to High-Risk Solely by Amplification.

Background: To identify variables predicting outcome in neuroblastoma patients assigned to the high-risk group solely by the presence of oncogene amplification (MNA).

Methods: Clinical characteristics, genomic information, and outcome of 190 patients solely assigned to high-risk neuroblastoma by MNA were analyzed and compared to 205 patients with stage 4 neuroblastoma aged ≥18 months with MNA (control group).

Results: Event-free survival (EFS) and overall survival (OS) at 10 years were 47% (95%-CI 39-54%) and 56% (95%-CI 49-63%), respectively, which was significantly better than EFS and OS of the control group (EFS 25%, 95%-CI 18-31%, < 0.001; OS 32% 95%-CI 25-39%, < 0.001). The presence of /p53-pathway gene alterations was associated with impaired 10-year EFS and OS (19% vs. 55%, and 19% vs. 67%, respectively; both < 0.001). In time-dependent multivariable analyses, alterations of RAS-/p53-pathway genes and the extent of the best primary tumor resection were the only independent prognostic variables for OS ( < 0.001 and = 0.011, respectively).

Conclusions: Neuroblastoma patients attributed to high risk solely by amplification have generally a more favorable outcome. Mutations of genes of the RAS and/or p53 pathways and incomplete resection are the main risk factors predicting poor outcome.