Abstract
BACKGROUND: Adult-onset medulloblastoma (aMB) represents less than 1% of adult brain malignancies. Adult treatment strategies remain poorly defined and are frequently extrapolated from pediatric protocols. This challenge is particularly pronounced in Latin America, where prospective data are lacking and access to diagnostics and treatment remains limited. MATERIAL AND METHODS: We conducted a prospective observational cohort study involving adult patients (≥16 years) with newly diagnosed aMB treated between May 2024 and March 2025 across a network of tertiary referral centers in Mexico, including the INCan and the INNN. Eligible patients were consecutively enrolled at diagnosis. This report presents the first 13 patients from this ongoing cohort. RESULTS: Median age was 28 years (IQR 21-32), and 53.8% were male. Tumor locations included cerebral hemispheres (53.8%), vermis (38.5%), and fourth ventricle (7.7%). Presenting symptoms were headache (100%), nausea/vomiting (92.3%), ataxia or cerebellar signs (76.9%), and others such as visual disturbances, cranial nerve deficits, and sensory complaints (30.8% each). Hydrocephalus was present in 92.3%, all requiring shunt placement. Metastatic disease (M1-M4) was found in 46.2%, while 53.8% were M0. Per Packer’s criteria, 92.3% had high-risk disease. Histologic subtypes were desmoplastic/nodular (76.9%) and classic (23.1%). Of 11 patients with molecular subgrouping, 54.5% were SHH-activated TP53 wild-type, 18.2% SHH-activated TP53-mutated, and 18.2% non-SHH/non-WNT. Most patients (84.6%) underwent subtotal resection or biopsy; only 2 had gross total resection. Craniospinal irradiation (CSI) at 36 Gy was administered to 92.3%, with a median tumor bed boost of 55.8 Gy. One patient received a posterior fossa boost (54 Gy). The median interval from surgery to radiotherapy was 116.5 days (range 24-187), and the overall treatment time was 46 days (range 26-69). Concurrent vincristine chemotherapy was given to 83.3%. One patient had neoadjuvant chemotherapy; 61.5% received adjuvant chemotherapy. The most common regimen was cisplatin, cyclophosphamide, and vincristine (46.2%), followed by temozolomide (15.4%). Adverse effects included gastrointestinal symptoms and anemia (23.1% each), neutropenia (15.4%), and ototoxicity and neuropathy (7.7% each). CONCLUSION: This first prospective Latin American study on aMB highlights the predominance of SHH-activated subtypes, frequent presentation with advanced disease, and significant delays in initiating radiotherapy. Despite limited resources, most patients received multimodal treatment. These findings emphasize the urgent need for earlier diagnosis, faster treatment initiation, and standardized care pathways for aMB in low- and middle-income countries