| Purpose: Studies have shown that the most common resistance mutation to tyrosine kinase inhibitors(TKIs)in lung adenocarcinoma with epidermal growth factor receptor(EGFR)mutation is the EGFR-T790 M mutation.With the continuous development of plasma-based liquid biopsy and the prominent advantages in clinical practice,plasma-based liquid biopsy has become more and more widely used in clinical application.In this study,we detected circulating tumor DNA(ctDNA)in plasma of patients with advanced lung adenocarcinoma to understand the clinical characteristics of acquired drug resistance of EGFR-T790 M,and to guide individual precise treatment.Patients and methods: A retrospective study was conducted to collect patients with primary lung adenocarcinoma diagnosed by pathology from November 2016 to October 2018 in Tumor Hospital Affiliated to Guangxi Medical University.The patients were sequenced by second generation sequencing or ddPCR after treatment progress with first-or second-generationEGFR-TKIs.At the same time,the relationship between the clinical characteristics of lung adenocarcinoma and T790 M status was analyzed statistically.Results: A total of 68 plasma samples were collected,of which 17 provided tissue samples.The plasma samples of 44 patients were detected by the Next-Generation Sequencing(NGS)and 24 by droplet digital Polymerase Chain Reaction(ddPCR).T790 M mutation was found in 43 cases,with a mutation rate of 58.8%(40/68).Among them,27 cases were T790 M positive by NGS and 13 cases were detected by ddPCR.The sensitivity was 61.3%(27/44)and54.2%(13/24)respectively.The study found that T790 M mutation was not related to age,sex,ECOG score(Eastern Cooperative Oncology Group,ECOG),smoking status,EGFR sensitive mutation type(19del and L858R),first or second generation EGFR-TKIs,brain metastasis.The mutation frequency of T790 M positive patients in median progression-free survival(mPFS)> 11 months was higher than that in < 11 months(79% vs.40%;odds ratio,4.516;95% CI,1.53-13.30;P = 0.006),and the PFS treated with first or second generation EGFR-TKIs was longer than that treated with T790 M negative patients(13.0 months vs.9.0 months;P = 0.04).In the study also found that patients treated with EGFR-TKIs at or above the second line were more likely to carry the EGFR T790 M mutation(76% vs.51%,P = 0.03)than those treated with first line.At the same time,17 tissue-matched samples were detected by second-generation sequencing,and the coincidence rate was 94%.Thirty-six of40 of T790 M positive patients(82.5%)received the third generation TKI treatment.Conclusions: In patients with advanced lung adenocarcinoma who failed to receive EGFR-TKIs in the first or second generation,PFS and lines of initialEGFR-TKIs were associated with T790 M mutation. |
