Diagnostic utility of liquid biopsies in pediatric brain tumors: a systematic review

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. Liquid biopsy has emerged as a promising, minimally invasive alternative for diagnosis and disease monitoring, particularly with the increasing emphasis on molecular characterization.

A systematic review was conducted in accordance with PRISMA 2020 guidelines. Electronic databases (PubMed/MEDLINE, Embase, Scopus, and Cochrane) were searched from inception to June 2025. A total of 831 records were screened independently by two reviewers, with discrepancies resolved by a third. Data extraction was performed independently by two reviewers using a standardized, pre-piloted form.

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 supported diagnostic utility. Comparative analysis in one study confirmed superior detection in CSF (20%) versus plasma (1.3%) and urine (0%).

CSF-based liquid biopsy demonstrates strong potential for molecular diagnosis, disease monitoring, and early relapse detection in pediatric brain tumors.