P14.27.b Long-Term Outcomes and Molecularly-Guided Management of Adult Medulloblastoma: Data From a Single-Institution Experience

Abstract BACKGROUND Medulloblastoma(MB) is an exceedingly rare malignancy in adults, with limited prospective data guiding its management. Although multimodal treatment remains the standard, recent molecular profiling has enabled the introduction of targeted therapies, such as SMO-inhibitors for SHH-activated tumors. This study aims to describe clinical characteristics, treatments - including the use of targeted therapy - outcomes, and long-term sequelae in a monocentric cohort of adult MB pts, providing insights to optimize future therapeutic strategies. MATERIAL AND METHODS We retrospectively analyzed adult MB pts treated at Veneto Institute of Oncology, Padua, Italy between November 2011 and February 2025. Clinical, molecular and treatment data, including extent of surgery and RT details were collected. Response was assessed using RANO criteria, treatment-related toxicity according to CTCAEv5.0. Survival outcomes were estimated using the K-M method. RESULTS We included 29 pts (median age 34ys, IQR 22-41; 44.5% males), with a median FU of 71ms (IQR 32-112). At diagnosis, 86% were symptomatic, 55% had an ECOG PS 0, and desmoplastic/nodular was the most frequent histology(48%). Molecular subgrouping was available in 45%, with SHH activation being the most common (31%). All pts received craniospinal-RT; 18 pts(62%) received adjuvant CT with cisplatin-etoposide±cyclophosphamide, 6(21%) cisplatin-lomustine±vincristine, 3(10%) an intensive pediatric regimen and 2(7%) did not received CT due to comorbidities. First-line CR was achieved in 65%. Overall, 38% experienced PD and 24% died. Three pts received vismodegib at recurrence: one (M0 stage, high-risk) received 3 cycles without toxicity, had PD at 3ms from vismodegib start and died at 30ms from diagnosis; one (M2 stage, high-risk) received 5 cycles without toxicity, had PD at 4ms and died at 64ms. One patient (M0 stage, high-risk) received 11 cycles, developed G1 toxicity and did not experience PD until now (11ms). Three patients received re-RT at PD. The 3-year PFS and OS rates were 78% and 92%, respectively. Stratified analyses suggested worse outcomes associated with high-risk class, subtotal resection, and lower baseline ECOG PS. Grade 3-4 toxicity occurred in 29%(7/24 evaluable). Long-term complications included neurocognitive impairment(21%) and RT-induced secondary malignancies (10%) at a median of 46ms. CONCLUSION Our findings confirm the clinical and biological heterogeneity of adult MB, highlighting the need for a multimodal approach. Long-term survivorship is often achievable, though late toxicities remain a concern. Vismodegib showed a significant impact on outcome. Future efforts should focus on integrating molecular profiling into routine practice to better stratify risk and personalize therapies, along with the adoption of treatment de-intensification strategies to mitigate long-term sequelae.