Improved Outcomes for Older Children, Adolescents, and Young Adults With Neuroblastoma in the Post-Immunotherapy Era:...

We describe clinical and biologic characteristics of neuroblastoma in older children, adolescents, and young adults (OCAYA); describe survival outcomes in the post-immunotherapy era; and identify if there is an age cut-off that best discriminates outcomes.

Patients diagnosed with neuroblastoma at ≥547 days between 2003 and 2022 from the International Neuroblastoma Risk Group Data Commons were compared by age subgroups. Recursive partitioning, dividing younger versus older at all monthly cut-points between 18 months and 15 years, was undertaken using Cox regression models of event-free survival (EFS), overall survival (OS), and OS post-relapse (OSPR). Kaplan-Meier curves of clinical/biologic subgroups were compared with log-rank tests.

7,835 patients met inclusion criteria: 18 months to <5 years (n = 5841), 5 to <10 years (n = 1488), 10 to <15 years (n = 357), and ≥15 years (n = 149) at diagnosis. Younger patients were more likely to have MYCN amplification (18 months to 5 years: 31%; 5-10 years: 15%) than older (10-15 years: 8%; ≥15 years: 7%) (p < 0.0001), metastatic disease (p < 0.0001), and high mitosis-karyorrhexis index (MKI) (p < 0.0001) and less likely to have diploid tumors (p < 0.001). Repeatedly dichotomizing the cohort, younger patients had superior EFS and OS (p < 0.05) for all cut-offs ≤40 months (hazard ratios: 1.1-1.3). Among high-risk OCAYA (International Neuroblastoma Staging System [INSS] Stage 4; n = 5005 [64% of cohort]), those diagnosed 2010-2022 had superior EFS/OS versus 2003-2009 in each age group (p < 0.0001). OSPR remained poor for all OCAYA (5-year OSPR 14% ± 0.7%).

For patients ≥547 days old, any age cut-off ≤40 months discriminated younger (superior EFS/OS) versus older patients; no cut-off was optimal. OCAYA diagnosed 2010-2022 (post-immunotherapy era) had superior outcomes versus 2003-2009. Stratification by comprehensive molecular biomarkers will likely best inform novel therapeutic strategies for OCAYA.