Management and outcome of children with high-risk neuroblastoma: insights from the Spanish Society of Pediatric Hematology and Oncology (SEHOP) neuroblastoma group on refractory and relapse/progressive disease

Abstract

Purpose Outcome for children with refractory and relapse/progressive high-risk neuroblastoma (HR-NB) remains poor, without an internationally agreed standard second-line approach. Heterogeneity in patients’ disease and treatment strategies challenges clinical management. The survival rate for patients with resistant disease does not exceed 20% at 5 years. The study’s aim was to analyze refractory and progressive HR-NB patients in a real-world setting to evaluate current clinical practices and optimize future approaches. Methods Data from patients diagnosed with refractory and relapse/progressive (R/R-P) HR-NB between January 2019 and December 2021 at six of the major Spanish neuroblastoma treating hospitals were collected and analyzed. Results A total of 67 episodes of R/R-P HR-NB were included. Treatments applied included chemotherapy (97%), immunotherapy (48%), consolidation (21%), local treatment (surgery and/or radiotherapy) (45%) and maintenance (16%), and were administered within a clinical trial (CT) in 34% of the episodes. Biopsy was performed in 37% of the tumors and 30% were profiled. Event-free survival (EFS) in our cohort was 20.9% and overall survival (OS) 32%. Significant survival advantage (in both OS and EFS) was observed in refractory episodes compared to relapse/progressive, in first events compared to successive, and when response or disease stabilization was achieved. MYCN status, presence of lymph node metastases, use of irinotecan or topotecan, and radiotherapy were also univariate predictors of OS. Conclusions Treatment of refractory and relapse/progressive HR-NB is highly heterogeneous. We confirm a poor outcome, although certain epidemiological and treatment-related factors have prognostic value. Molecular profiling and inclusion in CTs should be improved.