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 131I-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 male. Stage 4 NB with multisite 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 of 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 Omburtamab radioimmunotherapy significantly improves survival outcomes.

Purpose: We aim to describe the characteristics of patients with childhood-onset craniopharyngioma and to analyze factors that impair quality of life (QoL) in this population. Methods: multicenter national study including patients treated between 2008-2022, from 2 to 25 years of age diagnosed with craniopharyngioma. QoL was assessed once during patient’s follow-up by age-adapted versions Pediatric Quality of Life Inventory (PedsQL TM) questionnaire. Results: Sixty-six patients were included. Median age at diagnosis was 5 years (IQR 3-8), while median follow-up was 7.4 years (IQR 2.8-9.7). Most craniopharyngioma were suprasellar (93.9%) and 59.7% had hypothalamic involvement (HI). All patients underwent surgery, 44.4% received radiotherapy and 23.6%, intra-cystic therapy. Most frequent long-term complications were visual deficit (72.7%) and endocrine impairment (94.5%). Patients exhibited hypothyroidism requiring hormone replacement (92.4%), hypocortisolism (80.3%), diabetes insipidus (86.4%) and/or growth hormone therapy (50%). When parents evaluated QoL, PedsQL TM median score was 53.8 points out of 100 (IQR 41-71.6). Higher scores were noted when patients assessed their own QoL [median-score 64.8 (IQR 57.3-81.8)], observing statistical-significant differences (p=0.019). QoL was impaired by repeated surgeries (r -0.44; p=0.014), HI [median-score 51.5 (IQR 39-63.8) vs 76.4 (59-84.8); p=0.001], radiotherapy [median-score 51.9 (IQR 38.1-61.3) vs 63.8 (IQR 49-82.5); p=0.02] and longer follow-up (r-0.3; p=0.01). Conclusion: In our study, most patients had significant comorbidities and low overall QoL scores, which was mainly affected by repeated surgery, radiation, and HI. The complex management of these patients requires multidisciplinary teams that can warrant the hypothalamic preservation and prompt intervention to prevent and identify sequelae.