Dynamic Monitoring Of EGFR Mutation In Plasma Cell-Free DNA By Digital PCR

BackgroundNon-small cell lung cancer (NSCLC) represents approximately 85% of all lung cancers, which are the leading cause of cancer-related deaths in the world. Fortunately, EGFR-TKIs are dramatically effective in lung cancer with EGFR activating mutations. However, even in cases where there is high effectiveness, tolerance is acquired within 6 months to 12 months. Therefore It’s necessary to test EGFR mutation for identifying the right patients before EGFR-TKI treatment and monitor the EGFR mutation status during treatment. Nowadays, EGFR mutation testing in plasma cell-free DNA (cfDNA) from lung cancer patients is emerging as a valuable clinical tool. A new generation of PCR technique ddPCR were developed, which enabled the highly sensitive genotyping and the absolute quantification of mutant genesObjectivesThis study investigated the quantification and dynamic change of EGFR mutation status in plasma cfDNA by ddPCR technology to assess the clinical responce of EGFR-TKI therapy in NSCLC patients.Methods1. We retrospectively investigated 50 patients with NSCLC for their EGFR sensitive mutations and T790M mutation in matched pre、during- and post-TKI plasma samples, using ddPCR technology; 2. We retrospectively investigated 158 patients with NSCLC who ever received Erlotinib treatment and analyzed the survival curves of different EGFR mutation status (E19-Dels、L858R、negative).Results1. For E19-Dels and L858R, the plasma testing sensitivity and specificity, compared to the matched tumor tissues tested by ARMS, were 41.30% and 88.89%. The status of EGFR mutation changed according to the clinical response to Erlotinib for 8 of 9 patients.The study also demonstrated that monitoring the EGFR mutations in the blood allows for the detection of the T790M mutation up to 18 weeks before diseaseprogression is clinically evident. At the time of disease progression the T790M mutation was detected in plasma from 6 patients (50%); 2. There was no significant differences of PFS between E19-Dels and L858R(142 vs 97, P=0.113). For NSCLC patients without EGFR activating mutation, DCR was 52.4% (95% Cl 33.2-76.9). The median PFS and OS were 20 weeks and 51 weeks.ConclusionsQualitative and quantitative detecting of EGFR gene mutation by the highly sensitive and specific ddPCR assays provided a non-invasive assay to predict EGFR-TKI prognosis.