Detection of Plasma EGFR Mutations in NSCLC Patients with a Validated ddPCR Lung cfDNA Assay.

: The clinical utility of cell-free DNA (cfDNA) to assess mutations is increasing. However, there are limited studies determining their clinical validity and utility. The value of cfDNA assays in cancer management remains controversial. : In this study, we first evaluated the analytical performance of the ddPCR Lung cfDNA Assay. We next analyzed the concordance of the results with tissue amplification refractory mutation system PCR (ARMS-PCR) and plasma next-generation sequencing (NGS) genotyping. Finally, we assessed its clinical utility by exploring the association of cfDNA mutations with metastatic sites and the efficacy of EGFR-TKIs treatment. : The ddPCR Lung cfDNA Assay demonstrated a limit of blank of 1 droplet per reaction, an analytical specificity of 100%, and detection limit of 0.05%, 0.05%, and 0.1% for , , and , respectively. With tissue ARMS-PCR as a standard for comparison, the clinical sensitivity and specificity of ddPCR were 62.5% (15/24) and 100% (82/82) for , and 75.0% (15/20) and 94.2% (81/86) for , respectively. The ddPCR showed high concordance with NGS in determining cfDNA mutations. Patients with bone and/or brain metastasis showed a higher detection rate and mutant abundance of cfDNA mutations compared to those with other sites of metastasis. Moreover, EGFR-TKIs treatment was effective in patients with sensitive mutations in either plasma cfDNA or tumor tissue-derived DNA. : We validated in this study that the ddPCR Lung cfDNA Assay is reliable for detection of mutations in lung cancers, in terms of analytical performance, clinical validity and utility.