Clinical Outcomes and Toxicity of First-Line Intensive Chemotherapy in Infant Medulloblastoma: A Single-Center Cohort Study Following AIEOP Recommendations

Purpose: The long-term neurocognitive impact of craniospinal irradiation (CSI) in young children with medulloblastoma (MB) has driven the development of alternative strategies aimed at improving survival while delaying or avoiding CSI. Methods: We retrospectively analyzed a cohort of patients under 5 years of age with MB treated at Bambino Gesù Children’s Hospital between 2007–2023 with intensive chemotherapy regimens according to AIEOP recommendation. Clinical, radiological, histopathological, molecular, neurocognitive, and toxicity data were collected. Survival was estimated using the Kaplan–Meier method, with group comparisons by log-rank test. Results : Among 42 patients under 5 years, 25 met inclusion criteria (median age 25.3 months). Histology included classic (52%), desmoplastic/nodular (24%), extensive nodularity (16%), and large cell/anaplastic (8%). SHH was the most common molecular subgroup (52%), followed by Group 3 (32%) and Group 4 (16%). At a median follow-up of 95.7 months, 68% of patients were alive and in complete remission. Two- and 5-year OS were 80.0% and 65.9%, respectively; PFS was 72.0% and 67.8%. All patients experienced grade 3–4 hematological toxicity; late endocrine effects occurred in four patients and no other long-term toxicities were reported. Mean IQ was stable from diagnosis (85.3) to last follow up (83.4). Conclusion : Our retrospective study of infants MB treated with first-line intensive chemotherapy shows encouraging survival rates, better than reported in the literature to date. Importantly, neurocognitive function was preserved over time, supporting radiation-sparing strategies, and toxicity was manageable in all cases.