Diagnostic accuracy of droplet digital PCR (ddPCR) and amplification refractory mutation system PCR (ARMS-PCR) for detecting EGFR mutation in cell-free DNA of advanced lung cancer: A meta-analysis

Abstract

Background: Epidermal growth factor receptor (EGFR) mutation testing in plasma cell-free DNA (cfDNA) from advanced lung cancer patients is an emerging clinical tool. This non-invasive approach may offer genotyping information but prevent patients from the shortcomings of invasive and repeated biopsies. This meta-analysis was designed to determine the diagnostic accuracy of two common PCR systems, ddPCR and ARMS-PCR, for detecting EGFR mutation in cfDNA. Methods: A systematic search was carried out based on electronic databases. Data from eligible studies were extracted and pooled to calculate the sensitivity, specificity, diagnostic odds ratio (DOR), and area under the summary receiver-operating characteristic curve (AUROC), using tissue biopsy results as the standard method. Results: Twenty-three studies involving 4,725 cases were identified and included. The plasma testing sensitivity, specificity, DOR and AUROC, compared with the matched tumor tissues, were 71.7% (95% CI, 67.6%-75.5%), 96.4% (95% CI, 94.2%-97.9%), 39.3 (95% CI, 21.2-73.1), 0.87 (95% CI, 0.80-0.94) for ddPCR, and 65.3% (95% CI, 62.9%-67.6%), 98.2% (95% CI, 97.6%-98.7%), 52.8 (95% CI, 26.3-106.1), 0.71 (95% CI, 0.52-0.91) for ARMS-PCR, respectively. In studies simultaneously comparing the two platforms, we observed no significant difference in specificity (P=0.473) and sensitivity (P=0.960) between ddPCR and ARMS-PCR, regardless of EGFR mutation type, tumor stage and EGFR-TKI treatment. Conclusions: This study demonstrates that both ddPCR and ARMS-PCR have a high specificity with a practical sensitivity for detecting EGFR mutation in cfDNA of advanced lung cancer patients, which supports their application as a supplement or an alternative to tissue biopsy in clinical practice for genotyping. (Table Presented) .