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

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.

Wilms tumour event-free and overall survival in Southern and Eastern Europe: Pooled analyses of clinical data from four childhood cancer registries (1999-2017).

BACKGROUND: Wilms tumour (WT) management represents a success story in pediatric oncology. We aimed to assess, for the first time, the event-free survival (EFS) vs. overall survival (OS) in Southern and Eastern Europe (SEE) using harmonised clinical data collected by childhood cancer registries and to identify respective prognostic factors. METHODS: From 1999 to 2017, data for incident WT cases aged 0-14 years from 3 nationwide (Greece, Belarus and Slovenia) and one regional (Greater Poland) SEE registries were collected following common coding. Kaplan-Meier curves were constructed, and EFS vs. OS values were derived from Cox proportional hazard models by study variables. RESULTS: A total of 338 WT cases (45.6% males; median age, 3.19 years; age<5 years, 75%) were included in the analyses. Bilateral were 21 tumours (6.2%). Among the 317 unilateral cases, the majority (93.7%) received International Society of Pediatric Oncology-based protocols; EFS5-year was 85.1%, and OS5-year 91.1%; both outcomes were significantly worse in stage IV patients or in those with high-risk/unfavourable histology. Relapse rate among high-risk/unfavourable histology cases was 2.3 times higher than among low-intermediate risk/favourable histology cases, with respective death rate 5.6 times higher. Both relapse and death rates increased significantly in patients with advanced anatomical stage and high-risk/unfavourable histology. Finally, significantly worse was the outcome in bilateral tumours (OS5-year: 76.3%) vs. unilateral non-metastatic tumours (OS5-year: 94.7%). CONCLUSIONS: Our results delineate the potential of high-quality childhood cancer registration entailing clinical data to assess predictors of WT outcome over and beyond those derived from enrolment into clinical trials. Specifically, outcomes among children with WT residing in the four participating SEE countries were comparable with those reported by major cooperative international groups, albeit somehow inferior. Despite the excellent overall prognosis, however, subgroups of patients with advanced or bilateral disease and/or high-risk histology still suffer poor outcomes.