髄芽腫および非定型奇形腫様ラブドイド腫瘍（AT/RT）に対する臨床試験の現状と展望

Current Status and Prospects of Clinical Trials for Medulloblastoma and Atypical Teratoid/Rhabdoid Tumor

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・髄芽腫では，化学療法の強化により全脳全脊髄照射減量下での治療成績が向上する一方で，放射線脳壊死が新たな課題となっている．

・非定型奇形腫様ラブドイド腫瘍では，集学的治療により根治が期待される例が増えたものの，転移例は依然として予後不良であり，新薬の開発が急務である．

　Medulloblastoma (MB) and atypical teratoid/rhabdoid tumors (ATRT) are highly aggressive pediatric brain tumors that necessitate multimodal therapy. Historically, treatment strategies in Japan have varied across institutions due to the absence of standardized protocols. The establishment of the Japan Children's Cancer Group (JCCG) enabled nationwide clinical trials based on central pathological and molecular diagnoses. In MB, intensification of chemotherapy has enabled a reduction in the craniospinal irradiation (CSI) dose while maintaining survival outcomes. The ongoing JCCG MB19 trial has incorporated molecular subgrouping into risk stratification and employed high-dose chemotherapy (HDC) to balance survival and neurocognitive preservation. However, early reports on radiation necrosis, particularly after proton therapy, highlighted new safety concerns that require careful evaluation. The treatment outcomes for ATRT have gradually improved with multimodal regimens; however, the prognosis remains poor, especially in metastatic cases. The JCCG AT20 trial attempted to standardize treatment approaches by combining platinum, sarcoma-based agents, and frequent intrathecal methotrexate, followed by HDC and local radiotherapy. CSI was administered only to older patients with metastases. Despite these advances, the absence of new therapeutic agents has limited further progress. In the case of medulloblastoma, it is crucial to further investigate dose modulation in local radiotherapy to find a balance between efficacy and toxicity. Additionally, in the case of ATRT; there is an urgent need for novel treatments, such as targeted therapies and immunotherapies.