Cerebrospinal fluid Circulating Tumor DNA (ctDNA) as a biomarker for CNS metastases in Non-Small Cell Lung Cancer (NSCLC): a systematic review and meta-analysis comparing CSF ctDNA and traditional methods.

BACKGROUND

Brain metastasis is a common and serious complication in patients with non-small cell lung cancer (NSCLC), often associated with poor prognosis. While traditional diagnostic approaches such as magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) cytology are commonly used for detection, these methods have notable limitations. Circulating tumor DNA (ctDNA) in CSF has been reported as a superior alternative. This study evaluates the diagnostic test accuracy of CSF ctDNA for CNS metastases detection in patients with NSCLC, in comparison to CSF cytology, while also examining its potential prognostic value.

METHODS

A systematic search was conducted to identify studies that reported CSF ctDNA detection in NSCLC patients with brain or leptomeningeal metastases. Pooled detection rates, sensitivity, specificity, and diagnostic odds ratios were meta-analyzed. Heterogeneity and publication bias were assessed using standard statistical methods. Subgroup and sensitivity analysis were applied to identify and address source of high heterogeneity.

RESULTS

Twenty-six studies were included. The pooled detection rate of CSF ctDNA (86%, 95% CI: 0.79-0.91) was significantly higher than CSF cytology (60%, 95% CI: 36% % 81%). Diagnostic test accuracy analysis for CSF ctDNA showed high pooled sensitivity (91.8%, 95% CI: 74.2%-97.8%), specificity (93.5%, 95% CI: 76.7% - 98.5%) and diagnostic odds ratio (DOR) (93.51%, 95% CI: 13.85-631.44). Additionally, CSF ctDNA detected clinically relevant mutations that correlated with poorer overall survival, highlighting its prognostic potential.

CONCLUSION

CSF ctDNA demonstrates superior diagnostic accuracy for detecting CNS metastases in NSCLC compared to CSF cytology. Its molecular insights may support earlier detection and inform personalized treatment strategies. However, further validation in clinical settings is required.