Impact of Metastatic Patterns on Survival and Response to Therapy in Neuroblastoma.
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BACKGROUND: While the presence of metastases in neuroblastoma (NB) is a well-established prognostic factor, the clinical significance of dissemination patterns and tumour burden and their impact on response and survival remains poorly understood. OBJECTIVES: To characterise metastatic dissemination patterns and tumour burden in NB, evaluate their response to induction therapy, and determine their prognostic impact. METHODS: We retrospectively analysed 53 patients with metastatic NB between 2010 and 2024 in a reference tertiary care hospital and treated as per SIOPEN protocol or standard-of-care recommendations. Responses were recorded as per INRC 2017. Survival was estimated using Kaplan-Meier analysis, and associations between metastatic patterns and outcomes were evaluated by univariate analysis. RESULTS: The most frequent metastatic sites were bone (77%), regional lymph nodes (64%), and bone marrow (55%). MSI (metastatic site index) was 1 (n = 13), 2 (n = 13), 3 (n = 15), or ≥4 (n = 12). Overall response according to INRC after induction therapy achieved complete (n = 1), partial (n = 41), minor (n = 6) responses, stable (n = 4) or progressive disease (n = 1). Regarding metastatic response, regional and distant lymph nodes, renal and pulmonary decreased in size by 66%, 85%, 90 and 99%, respectively. The median SIOPEN score decreased from 16.5 to 0. Bone marrow infiltration disappeared in 82%. High tumour burden strongly correlated with poor outcomes. CONCLUSIONS: Presence of renal metastases, ascites, bone marrow infiltration, high tumour burden at diagnosis and post-induction pulmonary or renal metastases are negative prognostic markers. Incorporating these factors into risk stratification may guide personalised treatment strategies. Future work should elucidate the genomic background and underlying causes of these different metastatic patterns.