Circulating tumor DNA as a liquid biopsy for glioma detection in cerebrospinal fluid and plasma: A systematic review and meta-analysis.

Abstract

Introduction: Accurate molecular characterization of gliomas is essential for determining prognosis and guiding therapeutic decisions. In recent years, liquid biopsy for analysis of circulating tumor DNA (ctDNA) in blood or cerebrospinal fluid (CSF) has emerged as a promising, minimally invasive alternative. This study evaluates the existing literature on the utility of ctDNA detection in CSF and blood in patients with gliomas, with the goal of assessing its ability to identify mutations concordant with those detected in tumor tissue.

Methods: A systematic search was conducted up to April 30, 2026, to identify cohorts that evaluated the effectiveness of ctDNA-based liquid biopsies for gliomas. The primary assessed outcomes were the sensitivity and specificity of the liquid biopsies using CSF or plasma. A pooled sensitivity analysis was performed, as well as summary receiver operating characteristic (SROC) curves.

Results: Twenty-eight studies met the inclusion criteria, encompassing 613 patients. Meta-analysis of diagnostic performance revealed improved biomarker performance for CSF (Area under the curve [AUC] 0.95) ctDNA. Pooled sensitivity for ctDNA detection in patients with gliomas was higher in CSF 0.79 (95% CI, 0.69-0.85) than in plasma 0.29 (95% CI, 0.15-0.47), P < .0001.

Conclusion: The literature demonstrates a promising performance of ctDNA analysis in patients with diffuse gliomas as a liquid biopsy strategy. CSF ctDNA analysis exhibited superior sensitivity compared to plasma ctDNA. This meta-analysis supports the utility of ctDNA, particularly CSF ctDNA, as a complementary diagnostic tool in neuro-oncology.