Systematic review of diagnostic utility of liquid biopsy in pediatric brain tumors

Pediatric brain tumors (PBTs) are the most common solid malignancies in children, with an incidence of 5.61 per 100,000 in the United States. Current diagnostic approaches, including clinical evaluation, MRI, and tissue biopsy, are limited by challenges such as pseudoprogression, tumor heterogeneity, surgical inaccessibility, and procedural risk. Systematic review of studies published up to June 2025 evaluated diagnostic utility of liquid biopsy in PBTs. Twenty-seven studies encompassing 992 patients were included. Cerebrospinal fluid (CSF) was the most commonly studied biofluid (25/27 studies), demonstrating ctDNA detection rates of 51%-100%, particularly in diffuse midline glioma, medulloblastoma, and high-grade glioma. Plasma, evaluated in 11 studies, showed limited sensitivity (<45%), while urine-based detection was negligible. CSF methylation profiling, reported in five studies, demonstrated concordance with tumor tissue in up to 92% of cases. Additional biomarkers, including CPXM2 and miR-517a, further support diagnostic utility. Comparative analysis in one study confirmed superior detection in CSF (20%) versus plasma (1.3%) and urine (0%). The authors conclude that CSF-based liquid biopsy demonstrates strong potential for molecular diagnosis.