Real-world management and long-term outcomes in adolescent, young adult, and adult medulloblastoma: Experience from a monocentric series with multimodal and targeted approaches

Abstract Abstract Background Medulloblastoma (MB) is an exceedingly rare malignancy in adolescents and young adults (AYA) and adults. This study aims to describe clinical characteristics, treatments, including the use of targeted therapy, outcomes, and long-term sequelae in a single-center cohort of AYA/adult MB patients. Methods We retrospectively analyzed MB patients aged ≥16 years treated at Veneto Institute of Oncology, Padua, Italy, between 2011 and 2025. Clinical, molecular, and treatment data were collected. Treatment response was assessed using RAPNO criteria, and treatment-related toxicity according to CTCAE v5.0. Survival outcomes were estimated using the Kaplan-Meier method. Results We included 29 patients. At diagnosis, 86% were symptomatic, 55% had an ECOG performance status (PS) of 0, and desmoplastic/nodular was the most frequent histology (48%). Molecular subgrouping was available in 45%, with SHH activation as the most common subgroup (31%, 9/29 patients). All patients underwent craniospinal radiotherapy; adjuvant chemotherapy regimens included cisplatin-etoposide±cyclophosphamide (62%), cisplatin-lomustine±vincristine (21%), and intensive pediatric regimens (10%), while 2 patients (7%) did not receive chemotherapy due to comorbidities. First-line complete response was achieved in 65%. Overall, 38% experienced progression, and 24% died. Three patients received vismodegib at recurrence. Three-year PFS and OS rates were 78% and 92%. Stratified analyses indicated worse outcomes in patients with high-risk classification, subtotal resection, and lower baseline ECOG PS. Grade 3-4 toxicity occurred in 30%. Long-term complications included neurocognitive impairment (21%) and radiotherapy-induced secondary malignancies (10%). Conclusions Long-term survivorship is often achievable in AYA/adult MB, though late toxicities remain a concern. Molecular profiling supports risk stratification and therapy personalization. Long-term toxicities highlight the need for de-intensified strategies.