Analyzing EGFR Mutation Status Change In Different Sampling Time-points Of Blood Within One Day In Advanced Lung Adenocarcinoma

Background and ObjectiveEpidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)has emerged as an indispensable therapeutic strategy for advanced non-small-cell lung cancer(NSCLC)patients harboring epidermal growth factor receptor(EGFR)mutation,since it brings significant survival benefit as well as improving the quality of life.EGFR mutation detection is therefore a critical step in therapy selection and prognosis for advanced NSCLC.As a promisingly new detecting method,liquid biopsy in circulating tumor DNA(ctDNA)has non-invasive,homogeneity and dynamic monitoring characteristics.However,the relatively high rate of false negative hamper the use of liquid biopsy in ctDNA.We aimed to investigate whether the different sampling time-points within one day influence EGFR mutation status in plasma and evaluated the clinical outcomes according to the quantity analysis of EGFR mutation in ctDNA in advanced lung adenocarcinoma.Patients and MethodsEGFR-TKIs na?ve advanced lung adenocarcinoma patients who carried EGFR mutation in both tissues and ctDNA were enrolled in this study.Plasma samples were collected at three time-points within one day(at 8:00,11:00 and 14:00)for EGFR mutation analysis by droplet digital PCR(ddPCR).All patients received gefitinib as the first line therapy,the response was assessed by using the Response Evaluation Criteria in Solid Tumors(RECIST)1.1 every 2 months.ResultsTwenty-two advanced lung adenocarcinoma patients were enrolled in the study.In total 66 blood specimens,the median abundance of EGFR mutation was 7.13%(from 0 to 35.09%),and among them 6 specimens had less than 1.0% frequency of EGFR mutation.Moreover,there were still 1 time-point blood specimen lacking of EGFR mutation even by ddPCR.Totally,the abundance of EGFR mutation changed dynamically across different time-points within one day,but the difference was not significant(P = 0.557).The patients(one patient carrying L858 R and T790 M double mutations was excluded)were subdivided into two groups based on the relative quantity of EGFR mutation abundance(median,6.76%)in TKI-na?ve plasma samples(group high: > 6.76%,n = 10;group low: ≤ 6.76%,n = 11).The results demonstrated that patients with relatively high EGFR mutation abundance(> 6.76%)had a better response to gefitinib(P = 0.024).ConclusionThe release of ct DNA maybe a temporal heterogeneous process.The different sampling time-points within one day seems not has an influence on EGFR mutation status in ctDNA.The relative EGFR mutation abundance in ctDNA could predict benefit from EGFR-TKIs treatment for advanced lung adenocarcinoma.