Survival patterns of childhood neuroblastoma: an analysis of clinical data from Southern-Eastern European countries.

ABSTRACT

The prognosis of children with neuroblastoma (NBL) can be dismal with significant variations depending on the stage and biology of the tumor. We assessed the event-free (EFS) and overall (OS) survival using harmonized data from three Southern-Eastern European (SEE) countries. Data for 520 incident NBL cases (2009-2018) were collected from Greece, Slovenia and Russia. Kaplan-Meier curves were fitted, and EFS/OS were derived from Cox proportional models by study variables including the protocol-based risk-group (low/observation, intermediate, high). Over one-third of cases were coded in the high-risk group, of which 23 children (4.4%) received treatment with anti-ganglioside 2 (GD2) mAb. Survival rates were inferior in older (OS 5-year; 1.5-4.9 years 61%; EFS 5-year; 1.5-4.9 years 48%) compared to children younger than 1.5 years (OS 5-year; <1.5 years 91%; EFS 5-year; <1.5 years 78%). Predictors of poor OS included stage 4 (hazard ratio, HR OS 18.12, 95% confidence intervals, CI 3.47-94.54), N-myc amplification (HR OS 2.16, 95% CI 1.40-3.34), no surgical excision (HR OS 3.27, 95% CI 1.91-5.61) and relapse/progression (HR OS 5.46, 95% CI 3.23-9.24). Similar unfavorable EFS was found for the same subsets of patients. By contrast, treatment with anti-GD2 antibody in high-risk patients was associated with decreased risk of death or unfavorable events (HR OS 0.11, 95% CI 0.02-0.79; HR EFS 0.19, 95% CI 0.07-0.52). Our results confirm the outstanding prognosis of the early NBL stages, especially in children <1.5 years, and the improved outcomes of the anti-GD2 treatment in high-risk patients. Ongoing high-quality clinical cancer registration is needed to ensure comparability of survival across Europe and refine our understanding of the NBL biology.