What does this research mean for the field?

A multimodal treatment strategy incorporating reduced-dose proton-beam radiotherapy and intrathecal methotrexate achieves favorable 5-year survival outcomes in medulloblastoma patients aged over 3 years, though optimization is needed to mitigate neurotoxicity in high-risk patients. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This research aims to assess the effectiveness of a multimodal treatment strategy for medulloblastoma patients aged over 3 years.

June 26, 2026Open Access

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

Key Points

This research aims to assess the effectiveness of a multimodal treatment strategy for medulloblastoma patients aged over 3 years.
Included patients aged ≥3 years diagnosed with medulloblastoma from October 2019 to June 2025.
All patients received intrathecal methotrexate followed by reduced-dose proton-beam radiotherapy and high-dose chemotherapy with autologous stem cell transplantation.
Survival outcomes and toxicities were analyzed in 43 patients, consisting of average-risk and high-risk groups.
The 5-year progression-free survival (PFS) was 87.0%, and the overall survival (OS) was 85.7% for the entire cohort.
High-risk patients achieved a 5-year PFS of 92.9% and OS of 100%, with no transplant-related mortality observed.
Common late effects included endocrine dysfunction and hearing loss, particularly in high-risk patients exposed to high radiation doses.

Abstract

Abstract 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.

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