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
Authors: C.C. Li, Q. He, H. Liang, J. He, W. Liang
Journal: Annals of Oncology (2019)

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. Legal entity responsible for the study: The First Affiliated Hospital of Guangzhou Medical University. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.Table41PIndex methodIncluded studiesSensitivitySpecificityDORAURORddPCR1271.7% (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)ARMS-PCR1665.3% (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)Subgroup analysis of exon 19 deletion in two systemsddPCR973.2% (95% CI, 67.0%-78.7%)99.3% (95% CI, 98.2%-99.8%)170.8 (95% CI, 77.8-374.8)0.97 (95% CI, 0.92-1.00)ARMS-PCR1166.3% (95% CI, 60.9%-71.3%)99.3% (95% CI, 98.6%-99.7%)113.7 (95% CI, 39.9-323.4)0.65 (95% CI, 0.25-1.00)Subgroup analysis of L858R in two systemsddPCR1068.4% (95% CI, 61.7%-74.7%)98.8% (95% CI, 97.6%-99.5%)108.8 (95% CI, 55.3-214.3)0.97 (95% CI, 0.92-1.00)ARMS-PCR1161.6% (95% CI, 54.9%-68.0%)99.3% (95% CI, 98.7%-99.7%)110.1 (95% CI, 49.7-243.8)0.79 (95% CI, 0.42-1.00)Subgroup analysis of stage IIIB-IV and recurrence in two systemsddPCR472.5% (95% CI, 65.8%-78.6%)93.5% (95% CI, 89.1%-96.5%)35.1 (95% CI, 17.9-68.8)0.90 (95% CI, 0.82-1.00)ARMS-PCR573.7% (95% CI, 66.7%-79.8%)96.3% (95% CI, 92.1%-98.6%)52.1 (95% CI, 7.0-387.7)0.52 (95% CI, 0.00-1.00)Subgroup analysis of stage IA-IV in two systemsddPCR871.2% (95% CI, 65.8%-76.1%)98.8% (95% CI, 96.4%-99.7%)46.8 (95% CI, 16.1-136.5)0.88 (95% CI, 0.70-1.00)ARMS-PCR1164.2% (95% CI, 61.7%-66.7%)98.3% (95% CI, 97.7%-98.8%)60.7 (95% CI, 30.9-119.2)0.77 (95% CI, 0.55-0.99)Subgroup analysis of TKI-naive in two systemsddPCR571.7% (95% CI, 65.4%-77.4%)96.5% (95% CI, 93.9%-98.2%)51.9 (95% CI, 24.8-108.7)0.90 (95% CI, 0.81-0.99)ARMS-PCR563.9% (95% CI, 57.4%-70.1%)96.7% (95% CI, 94.1%-98.4%)41.9 (95% CI, 9.6-183.6)0.60 (95% CI, 0.04-1.00)Subgroup analysis of previous-TKI in two systemsddPCR774.1% (95% CI, 68.2%-79.4%)95.4% (95% CI, 87.1%-99.0%)19.9 (95% CI, 5.8-68.9)0.84 (95% CI, 0.73-95.8)ARMS-PCR865.4% (95% CI, 62.8%-77.9%)98.5% (95% CI, 97.9%-99.0%)72.6 (95% CI, 25.6-205.7)0.75 (95% CI, 0.49-1.00) Open table in a new tab