Neuroblastoma in Infants: Long-Term Survival From INES Protocols A SIOPEN Study

Objectives: Neuroblastoma is the most common extracranial solid tumor in infants, with a possibility of spontaneous regression even in disseminated disease. Despite an overall good prognosis, relapse can worsen the outcome for some patients. A long-term analysis is crucial to identify subgroups of patients with poorer prognosis, assessing the risks of late relapse, progression or long-term toxicity associated with multimodal treatment in very young children. Methods: Estimation of the 10-year event-free and overall survivals in 750 infants under 12 months with neuroblastoma, enrolled in the prospective INES protocols between 1999 and 2004. Follow-up data from INES patients were updated, and survival analyses were performed in order to determine prognostic factors such as age, stage, genomic profile, or MYCN amplification. Results: Overall, 10-year overall survival was 91.1% ± 1.0%, and 10-year event-free survival was 82.4% ± 1.4%, with significantly better outcomes in infants under 6 months compared with those aged 6–12 months, even considering the MYCN-amplified tumors only. MYCN amplification was the strongest prognostic factor and was correlated with lower survival in patients with metastatic disease. Discussion: Survival in patients less than 12 months remains excellent and stable even at long term, as a 10-year follow-up did not change the number of events. However, survival in MYCN-amplified tumors remained poor. Patients with metastatic tumors require accurate risk stratification. For each treatment group, there was no significant difference in long-term outcomes compared with previous publications from INES. No lethal toxicity affecting long-term survival occurred.