Clinical, toxicity and long-term neurocognitive outcomes 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 and 2023 with intensive chemotherapy regimens according to AIEOP recommendation. Clinical, radiological, histopathological, molecular, neurocognitive, and toxicity data were collected. Results: Among 42 patients under 5 years, 25 met inclusion criteria (median age 25.3 months, range 5.0–51.3). Histology included classic (52%), desmoplastic/nodular (20%), extensive nodularity (16%), and large cell/anaplastic (12%). 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% were alive in complete remission. Two- and 5-year overall survival (OS) were 80.0% (95%CI: 58.4–91.1) and 65.9% (95%CI: 42.8–81.4); progression-free survival (PFS) was 68.0% (95%CI: 46.1–82.5) and 63.8% (95%CI: 41.8–79.2). Survival differed by risk group: low-risk patients achieved 100% OS and PFS, standard-risk intermediate, high-risk lowest. All experienced grade 3–4 hematological toxicity; late endocrine effects occurred in four patients, no other long-term toxicities reported. median IQ was stable from diagnosis (885.3) to last follow-up (8392.5.4). Conclusion: Our retrospective study of infants MB treated with first-line intensive chemotherapy shows encouraging survival rates. Importantly, neurocognitive function was preserved over time, supporting radiation-sparing strategies, and toxicity was manageable in all cases.