Prognostic Impact of Treatment Modalities, Including Targeted Compartmental Radio‐Immunotherapy, in a Cohort of Neuroblastoma Patients With CNS Metastases at Relapse

ABSTRACT Introduction Neuroblastoma (NB) with central nervous system (CNS) metastases is rare at diagnosis, but occurs more often during relapse/progression. Patients with CNS metastases face a dismal prognosis, with no standardized curative treatment available. Novel therapeutic approaches, such as intraventricular radio‐immunotherapy with 131 I‐omburtamab (Omb), have been developed. In this study, we report a retrospective, single‐tertiary center analysis of a 23‐year cohort of NB patients with CNS metastases, highlighting current treatment strategies. Patients and Methods Retrospective data analysis of all NB patients with CNS metastases treated at Hospital Sant Joan de Déu, Barcelona, from January 2000 to January 2023. Patient characteristics at diagnosis, first‐line treatment, relapse patterns, and CNS metastasis management were analyzed in search of risk variables and survival outcomes. Results CNS metastases at relapse were identified in 39/185 (21.1%) patients. Median age at diagnosis was 2.7 years, and 24/39 were male. Stage 4 NB with multisite compartment metastases accounted for most cases (92.2%). CNS events occurred predominantly at first relapse (29/39, 74.4%) and with neurological symptoms (23/38, 60.5%). MCYN amplification and concomitant extra‐CNS metastases at CNS relapse were associated with poorer overall survival (OS) ( p = 0.018 and p = 0.0059, respectively). Neurological symptoms upon relapse significantly increased the risk for subsequent CNS events ( p = 0.028). Curative‐intent treatment was attempted in 34/39 (87.2%) patients. After adjusting for immortal time bias, RT plus Omb significantly improved OS ( p < 0.0001). Conclusions In our experience, MYCN amplification and concomitant extra‐CNS metastases at CNS relapse significantly decrease OS. Multimodal treatment, including 131 I‐omburtamab radioimmunotherapy, significantly improves survival outcomes.