Diagnostic accuracy of circulating free DNA testing for the detection of KRAS mutations in non-small cell lung cancer: A systematic review and meta-analysis

Kirsten rat sarcoma viral oncogene homolog (KRAS) gene encodes a GTPase that acts as a molecular switch for intracellular signal transduction, promoting cell growth and proliferation. Mutations in the KRAS gene represent important biomarkers for NSCLC targeted therapy. However, detection of KRAS mutations in tissues has shown some limitations. During the last years, analyses of circulating free DNA (cfDNA) has emerged as an alternative and minimally invasive, approach to investigate tumor molecular changes. Here, we assessed the diagnostic performance of cfDNA analysis, compared to tissues through a meta-analysis and systematic review of existing literature. From 561 candidate papers, we finally identified 40 studies, including 2,805 NSCLC patients. We extracted values relating to the number of true-positive, false-positive, false-negative, and true-negative. Pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio, each with 95% CI, were calculated. A summary receiver operating characteristic curve and the area under curve (AUC) were used to evaluate the overall diagnostic performance. The pooled sensitivity was 0.71 (95% CI 0.68-0.74) and the specificity was 0.93 (95% CI 0.92-0.94). The diagnostic odds ratio was 35.24 (95% CI 24.88-49.91) and the area under the curve was 0.92 (SE = 0.094). These results provide evidence that detection of KRAS mutation using cfDNA testing is of adequate diagnostic accuracy thus offering to the clinicians a new promising screening test for NSCLC patients.