Pattern and predictors of sites of relapse in neuroblastoma: A report from the International Neuroblastoma Risk Group (INRG) project.

Abstract

We sought to analyze biologic, clinical, and prognostic differences according to pattern of failure at the time of first relapse in neuroblastoma. Children <21years diagnosed with neuroblastoma between 1989 and 2017 with known site of first relapse (isolated local vs. distant only vs. combined local and distant sites) were identified from the International Neuroblastoma Risk Group (INRG) database. Data were compared between sites of relapse according to clinical features, biologic features, initial treatment, time to first relapse, and overall survival (OS) from time of first relapse. Pattern of first relapse among 1833 children was 19% isolated local; 65% distant only; and 16% combined sites. All evaluated clinical and biologic variables with exception of tumor diagnosis differed statistically by relapse pattern, with patients with isolated local failure having more favorable prognostic features. Patients with stage 3 disease were more likely to have isolated local failure compared to all other stages (49% vs. 16%; p<.001). OS significantly differed by relapse pattern (5-year OS±SE): isolated local: 64%±3%; distant only: 23%±2%; and combined: 26%±4% (p<.001). After controlling for age, stage, and MYCN status, patients with isolated local failure (adjusted hazard ratio [HR]=0.46; 95% confidence interval [CI]: 0.33-0.62; p<.001) and distant-only failure (adjusted HR=0.57; 95% CI: 0.45-0.71; p<.001) remained at decreased risk for death as compared to patients with combined failure. Patients with distant-only and combined failures have a higher proportion of unfavorable clinical and biological features, and a lower survival than those with isolated local relapse.