Tumor-Treating Fields and Related Treatments in the Management of Pediatric Brain Tumors

Pediatric primary brain tumors pose significant therapeutic challenges due to their aggressive nature and the critical environment of the developing brain. Traditional modalities like surgery, chemotherapy, and radiotherapy often achieve limited success in high-grade gliomas and embryonal tumors. Tumor-treating fields (TTfields), a non-invasive therapy delivering alternating electric fields, has emerged as a promising approach to disrupt tumor cell division through mechanisms such as mitotic disruption, DNA damage, and tumor microenvironment modulation. TTfields are thought to selectively target dividing tumor cells while sparing healthy, non-dividing cells. While TTfields therapy is FDA-approved for the management of glioblastoma and other cancers, its application in pediatric brain tumors remains under investigation. Preclinical studies reveal its potential in medulloblastoma and ependymoma models, while observational data suggest its safety and feasibility in children. Current research focuses on optimizing TTfields' efficacy through advanced technologies, including high-intensity arrays, skull remodeling, and integration with immunotherapies such as immune checkpoint inhibitors. Innovative device-based therapies like magnetic field-based technologies further expand the treatment possibilities. As clinical trials progress, TTfields and related modalities offer hope for addressing unmet needs in pediatric neuro-oncology, especially for tumors in challenging locations. Future directions include biomarker identification, tailored protocols, and novel therapeutic combinations to enhance outcomes in pediatric brain tumor management.