Abstract

Abstract BACKGROUND Leptomeningeal metastasis (LM) is a life-threatening and quickly advancing complication in patients with solid cancer. Reliable diagnosis is challenging. CSF cytology remains the standard diagnostic test for LM, though the sensitivity has been reportedly at un-satisfactory levels ranging 40 to 60% in the literature. We evaluated the diagnostic accuracy of CSF liquid biopsy and advanced magnetic resonance imaging (MRI) for detecting LM in patients with solid cancers. MATERIAL AND METHODS A systematic search was conducted to identify all published diagnostic accuracy studies on CSF liquid biopsies and MRI on electronic databases with registration for PROSPERO. Articles were selected based on pre-defined criteria following the PRISMA 2020 statement. Assessment of Risk of Bias (ROB) was based on QUADAS 2. RESULTS The search yielded 3790 citations to screen between January 2000 to March 2022. Ten studies with 668 patients were included in the final analysis: seven studies of circulating tumor cells (CTC), five studies of MRI, and two studies of cell-free tumor DNA (ctDNA). The pooled prevalence of LM was 50.9% (340/668). The sensitivity was calculated presenting synthetic results as follows: CTC, 87.0% [95% CI: 77.9-92.6]; ctDNA, 97.9% [19.3-100]; MRI 59.4% [60.7-76.9]; cytology, 71.9% [54.7-82.9].The synthesized specificity was as follows: CTC, 93.8% [86.9-97.2]; ctDNA, 89.0% [25.3-99.5]; MRI 97.6% [77.3-99.8]. The diagnostic odds ratio was 100.6 (29.38-344.09) for CTC and 93.3 (88.42-1034.05) for MRI. ROB assessment showed high risk sources in domains of patient selection and index test. CONCLUSION his study showed a better sensitivity of CSF cytology than the reports in the literature. Novel CSF liquid biopsies had sufficient sensitivities, and advanced MRI had a high specificity. Cytology and the new diagnostic methods are complementary and may offer early diagnosis and improved diagnostic accuracy for LM in patients with solid cancers. Further research is required to specify the threshold values and to construct standards of biomarker-driven and less invasive approach for individual cancers, and they would facilitate clinical trials for LM in the era of targeted therapy.

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