Optimization of chemotherapy in multimodality treatment for pediatric brain tumors

Abstract

The clinical practice for pediatric brain tumors in Japan is undergoing considerable changes. Historically, radiotherapy has been the mainstay of brain tumor treatment, with chemotherapy playing an ancillary role. However, owing to the limitations of intensified radiotherapy and the occurrence of late comorbidities, there has been a shift toward a multidisciplinary approach that includes chemotherapy. Numerous clinical trials aimed at optimizing treatment are currently being conducted in Japan and internationally. Effective collaboration among various specialists is crucial for optimizing this multidisciplinary approach. With the establishment of the Japan Childhood Cancer Group (JCCG), the infrastructure for advanced multidisciplinary treatment in multi-institutional settings has been developed. Consequently, several clinical trials have been launched in rapid succession, including the EPN1501 trial for ependymoma, MB19 trial for medulloblastoma, AT20 trial for atypical teratoid rhabdoid tumors, and CNSGCT2021 trial for germ cell tumors of the central nervous system. All these trials aim to optimize treatment to minimize late complications associated with radiotherapy while maintaining treatment intensity by chemotherapy. In addition, the development of molecular targeted agents, particularly for gliomas, is advancing. The approval of NTRK inhibitors, followed by BRAF and MEK inhibitors, has broadened treatment options. The importance of early and aggressive genetic testing has increased. In future, it will be essential to determine how to effectively integrate novel targeted therapies with conventional treatments. In this paper, we provide an overview of the current status and prospects for optimizing the multidisciplinary treatment of pediatric brain tumors.