Diagnostic test accuracy of droplet digital PCR for the detection of EGFR mutation (T790M) in plasma: systematic review and meta-analysis

Abstract Background T790M mutation was a primary lead cause in the acquired resistance to EGFR-TKIs confirmed in earlier studies. Since the shortcomings of tumor tissue detection are well known, the liquid biopsy is more appropriate to track T790M status. We assessed the accuracy and clinical significance of the droplet digital PCR (ddPCR) detection of T790M mutation in plasma. Methods We retrieved PubMed, Embase, Cochrane, and Web of science with no limitation of language and publication year. Summary sensitivity and specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio of detection of EGFR T790M status were calculated from extracted data from included articles. The summary receiver operating curve (SROC), diagnostic odds ratio (DOR), and the area under the summary receiver operating curve (AUC) was used to assess the overall diagnostic accuracy. I2 and meta-regression were used to evaluate heterogeneity and the source of heterogeneity, respectively. Result We identified 15 studies in the total search of 1364 reports, including 427 paired tissue and plasma samples. The pooled sensitivity and the pooled specificity were 0.68 (95% CI 0.61-0.75) and 0.85 (95% CI 0.75-0.91) by the bivariate model, respectively. The AUC and the pooled DOR were 0.78 (95% CI 0.74-0.81) and 12 (95% CI 7-22), respectively. None of the cofactors could account for the heterogeneity. Conclusion The plasma analysis is of a promising performance to screen EGFR-T790M mutation status by ddPCR.