ID #750 Treatment Outcomes of Medulloblastoma Aged Over 3 Years: Efficacy of Reduced-Dose Proton-Beam Radiotherapy, Intrathecal Methotrexate, and Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation
Hee Won Cho, Ki Woong Sung, Ji Won LeeAbstract
Background
Reducing radiation exposure while maintaining disease control remains a major challenge in the treatment of medulloblastoma (MB). We evaluated a multimodal strategy incorporating reduced-dose proton-beam radiotherapy (RT), intrathecal methotrexate (IT-MTX), and tandem high-dose chemotherapy with autologous stem cell transplantation (HDCT/auto-SCT) for high-risk (HR) patients.
Methods
Patients aged ≥3 years diagnosed with MB between October 2019 and June 2025 were included. All patients received induction chemotherapy with IT-MTX followed by proton-beam RT. Average-risk (AR) patients received CSI of 18 Gy, whereas HR patients received CSI of 23.4 Gy. Local boost doses were adjusted according to residual disease. HR patients were scheduled for tandem HDCT/auto-SCT with age-adjusted conditioning regimens. Survival outcomes, acute toxicities and late effects were analyzed.
Results
Forty-three patients (23 AR, 20 HR) were analyzed, with a median age of 10.4 years. The 5-year progression-free survival (PFS) and overall survival (OS) for the entire cohort were 87.0% and 85.7%, respectively. AR patients demonstrated 5-year PFS and OS of 82.9% and 80.0%, whereas HR patients achieved 92.9% and 100%, respectively. Relapse occurred in three AR patients and one HR patient; all relapses presented with metastatic disease. No significant differences in PFS or OS were observed according to residual tumor status, metastatic stage, molecular subgroup, or CSI dose. Among HR patients, 17 underwent at least one HDCT/auto-SCT and 12 completed tandem transplantation, with no transplant-related mortality. Symptomatic RN developed in four patients (9.4%), exclusively in HR patients, predominantly involving brainstem or spinal cord regions receiving doses up to 54 Gy. Common late effects included endocrine dysfunction and hearing loss.
Conclusions
Reduced-dose proton-beam radiotherapy combined with IT-MTX achieved favorable survival outcomes in patients with MB aged ≥3 years. While this approach appears feasible, careful optimization of IT-MTX scheduling and HDCT intensity is warranted, particularly to mitigate radiation-induced neurotoxicity in HR patients.