Association of Circulating Tumor DNA With Brain Metastases: A Systematic Review and Meta-Analysis
Shaobo Yang1, Zongheng Zhang1, Hao Dong1
1Department of Neurosurgery, Changde Hospital, Xiangya School of Medicine, Central South University (The First People's Hospital of Changde City), Changde, Hunan, China.
CNS Neuroscience & Therapeutics
|June 3, 2026
Summary
Circulating tumor DNA (ctDNA) can help detect brain metastases. Plasma ctDNA indicates metastatic risk, while cerebrospinal fluid (CSF) ctDNA offers prognostic value for survival in brain metastases patients.
Area of Science:
- Oncology
- Biomarkers
- Genomics
Background:
- Brain metastases are a significant cause of mortality in advanced solid tumors.
- Early detection and prognostic assessment of brain metastases remain challenging.
- Circulating tumor DNA (ctDNA) offers a minimally invasive approach to monitor tumor behavior and molecular diversity.
Purpose of the Study:
- To systematically evaluate the diagnostic and prognostic value of ctDNA in brain metastases.
- To assess the complementary roles of plasma and cerebrospinal fluid (CSF) ctDNA.
- To determine the utility of ctDNA in improving risk assessment and treatment decisions for brain metastases.
Main Methods:
- Systematic literature search of multiple databases up to January 2025.
- Inclusion of 15 studies with 1763 participants.
- Meta-analysis using fixed-effects or random-effects models to calculate pooled ORs, SMDs, and HRs with 95% CIs.
Main Results:
- ctDNA positivity was significantly associated with an increased risk of brain metastases (OR = 1.67).
- Next-generation sequencing (NGS) demonstrated higher predictive performance (OR = 5.50).
- Plasma ctDNA levels were higher in patients with brain metastases (SMD = 0.51), while CSF ctDNA positivity correlated with worse overall survival (HR = 2.75).
Conclusions:
- Plasma ctDNA serves as a non-invasive biomarker for systemic metastatic risk.
- CSF ctDNA provides superior prognostic value for intracranial disease.
- Combined use of plasma and CSF ctDNA can enhance risk assessment and guide treatment decisions in brain metastases.
