ID #970 Long-term outcomes and treatment-related toxicities in pediatric high-risk medulloblastoma: a single-center experience
Rossana Pavone, Giada Del Baldo, Valentina Di Ruscio, Antonella Cacchione, Iside Alessi, Giacomina Megaro, Giulia Albino, Andrea De Salvo, Stefania Colafati, Sabrina Rossi, Evelina Miele, Andrea Carai, Sabina Vennarini, Angela MastronuzziAbstract
Background
Radiotherapy is a cornerstone in pediatric medulloblastoma (MB) treatment, with modern techniques aimed at reducing long-term toxicity. However, long-term outcome and toxicity data from patients treated outside international prospective protocols remain limited.
Methods
We retrospectively analyzed 51 pediatric patients with MB requiring radiotherapy managed at Bambino Gesù Children’s Hospital between 2009 and 2023. Median age at diagnosis was 8 years (range 1-19). Forty-nine patients were treated according to AIEOP national recommendations for high-risk MB, while two infant MB patients received re-irradiation with proton therapy (PT) and temozolomide at relapse. Twenty-three patients underwent craniospinal-PT and 28 photon radiotherapy (pRT). Clinical presentation, molecular features, survival outcomes, relapse patterns, treatment-related toxicities, and causes of death were evaluated.
Results
Median follow-up was 5 years (range 0-13). Two and five-year OS were 88.2% and 77.3%, while PFS was 81.6% and 65.4%, respectively. Seventeen patients relapsed, with a survival rate of 18% after second-line therapy. Median time from pRT/PT to relapse was 7 months. Overall, 17 deaths occurred, including 3 treatment-related or second malignancy deaths. No statistically significant survival differences were observed by histology, metastatic status, molecular subgroup, or radiation modality, although known trends were confirmed. At last follow-up, ototoxicity was limited (14%, Brock grade 1-2). Endocrine toxicities were frequent: central hypothyroidism in 19/51 patients (37%), GH deficiency in 22/51 (43%), adrenal insufficiency in 5/51 (10%), hypergonadotropic hypogonadism in 3/51 (6%), and metabolic disorders in 2/51 (4%), with higher rates of gonadal and metabolic toxicity after pRT. No cardiopulmonary dysfunction occurred after craniospinal irradiation. Neurocognitive evaluation (n = 42) showed median IQ decline of 8 points, with greater deterioration observed after pRT compared to PT.
Conclusions
Outcomes and toxicity patterns align with the literature, and PT appears to reduce neurocognitive and selected endocrine sequelae. Despite these trends, the small cohort limits the robustness of the conclusions.