Pediatric brain tumor: Recent advances in clinical practice in Japan

Abstract

With the introduction of integrated diagnosis in the revision of the 2016 World Health Organization (WHO) classification, the clinical management of pediatric brain tumors has undergone significant changes. Pediatric gliomas frequently harbor targetable genetic alterations, such as BRAF V600E and NTRK fusions, and rarely have adult-type genetic alterations such as IDH mutations. The use of immune-checkpoint inhibitors is a promising strategy for a small genetic subgroup of pediatric gliomas. Treatment strategies based on genetic alterations determined by multigene testing are now required. In contrast, medulloblastomas (MBs) have a few directly targetable abnormalities; however, precise risk stratification has become possible through detailed genetic analysis. Radiotherapy, including high-dose craniospinal irradiation (CSI), is still the main treatment strategy. A recently published study from the Japan Pediatric Brain Tumor Consortium (JPBTC) revealed promising results with high-dose chemotherapy (HDC). High-risk MB patients treated with HDC added to the main treatment strategy achieved more favorable outcomes than standard-risk MB patients treated without HDC. Treatment optimization based on genetic subgroups is necessary. After the identification of specific genetic alterations in an atypical teratoid rhabdoid tumor (ATRT), an increased number of patients with ATRT have been reported. Although the efficacies of radiation therapy and intrathecal chemotherapy are well known, the clinical benefits of treatment strategies including CSI are unknown. The standard treatment of ATRT is still under development.