Diagnostic accuracy of cerebrospinal fluid liquid biopsy and MRI for leptomeningeal metastases in solid cancers: A systematic review and meta-analysis

BACKGROUND: Cerebrospinal fluid (CSF) cytology remains the gold standard approach for diagnosing of leptomeningeal metastases (LM), but has clinical problems due to its low sensitivity. This systemic review and meta-analysis evaluated the diagnostic accuracy of the novel CSF biomarkers of liquid biopsy and magnetic resonance imaging (MRI) for detecting LM in patients with solid cancers. METHODS: A systematic search of electronic databases was conducted to identify all published diagnostic accuracy studies on CSF liquid biopsies and MRI since January 2000 with registration for PROSPERO (#CRD42022301988). Articles were selected based on pre-defined inclusion and exclusion criteria following the PRISMA 2020 statement. RESULTS: The search yielded 3790 citations, and 10 studies with 668 patients were included in the final analysis. The pooled prevalence of LM was 50.9% (340/668). The respective sensitivity and specificity for index tests were as follows: circulating tumor cells (CTC), 87.0% (95% confidence interval [CI] 77.9–92.6%) and 93.8% (86.9–97.2%); cell-free tumor DNA, 97.9% (19.3–100%) and 89.0% (25.3–99.5%); MRI 59.4% (60.7–76.9%) and 97.6% (77.3–99.8%); cytology, 71.9% (54.7–82.9%) and 100%. The diagnostic odds ratio was 100.6 (29.38–344.09) for CTC and 93.3 (88.42–1034.05) for MRI. CONCLUSION: Novel CSF liquid biopsies and MRI may offer improved diagnostic accuracy for LM from solid cancers; however, further research is required to specify the threshold values and to construct standards for individual primary cancers.