Outcomes for Patients Aged 12–18 Months With Metastatic MYCN Non-Amplified Neuroblastoma and Unfavorable Biologic Features (“Mixed Biology Toddlers”): A Report From the International Neuroblastoma Risk Group (INRG) Project

Background

Toddlers (age 365–<547 days) with MYCN non-amplified (MYCN-NA) metastatic neuroblastoma (NBL) that have at least one unfavorable biologic feature (“mixed biology toddlers”) are a rare NBL subgroup in need of further study.

Methods

Using the International Neuroblastoma Risk Group (INRG) Data Commons, we identified all toddlers with newly diagnosed metastatic, MYCN-NA NBL. Unfavorable biologic features included (1) unfavorable histology, (2) DNA index ≤1, (3) 1p loss of heterozygosity (LOH), and (4) 11q LOH. Kaplan–Meier curves of event-free survival (EFS) and overall survival (OS) were generated and compared using a log rank test; Cox proportional hazard regression models were used for multivariable analysis.

Results

Of the 450 patients identified, 157 had ≥1 unfavorable biologic feature and 26 had all favorable features. After adjusting for unfavorable biologic features, only high ferritin and high lactate dehydrogenase (LDH) remained significantly associated with worse EFS and OS. A total of 5-year EFS for mixed biology toddlers was 74.3% versus 88.5% for those with all favorable biologic features; 5-year OS was 79.3% versus 100%, respectively.

Conclusion

Mixed biology toddlers have lower EFS and OS compared to those whose tumors have favorable biologic features. Inclusion in high-risk NBL trials should be considered for this rare subgroup.