Correlation Between CT Signs,Tumor Markers And T790M Mutation After EGFR-TKIs Failure In Advanced Lung Adenocarcinoma

ObjectiveThe aim of our research was to investigate the association between CT signs,tumor markers and T790M mutation after EGFR-TKIs resistance in advanced lung adenocarcinoma.So that it can help distinguish the dominant population of T790M mutation and optimize the detection of T790M mutation after the failure of EGFR-TKIs treatment.MethodsA retrospective collection of 237 patients diagnosed as advanced lung adenocarcinoma who were EGFR mutation-positive and treated with first-generation or second-generation from June 2018 to May 2020 in our hospital.All of the patients accepted rebiopsy and EGFR gene testing after the failure of EGFR-TKI therapy.We first analyzed the mechanism of drug resistance and the clinical characteristics of secondary mutation of T790M.A total of 135 patients who showed progress in radiological findings and underwent tissue puncture in primary lung lesion were screened out.We then divided them into positive group and negative group according to the mutation status of T790M at the time of second biopsy.The clinical characteristics,CT signs of the primary tumor and tumor markers of the patient before rebiopsy were statistically analyzed between groups to obtain the influencing factors of acquired T790M mutation.The variables with P<0.10 in univariate analysis were included in multivariate analysis,and binary logistic regression analysis showed independent risk factors for T790M mutation.ResultsThe mean age of 237 patients was 58.8±9.9 years old.Stage IV lung cancer accounted for 93.7%(222/237).EGFR exon 19 deletion mutation accounted for 57.4%(136/237)and EGFR exon 21 L858R accounted for 37.6%(89/237)in the initial mutations of EGFR.The total mutation rate was 3.6%(127/237).Small cell transformation occurred in 8(3.4%)patients afier TKI targeted therapy.Univariate analysis revealed that secondary T790M mutation was associated with smoking history(P=0.047),initial EGFR mutation status(P=0.001)and duration of TKI treatment(P=0.033).Non-smoking patients with EGFR exon 19 deletion mutation as initial mutation who receive long-term TKI therapy showed a high prevalence of T790M mutation.CT signs of air bronchogram(P=0.008),pleural tag(P=0.020)and the high expression of cytokeratin fragment 19(CYFRA21-1)(P=0.049)were correlated with T790M mutation.Logistic regression analysis revealed that later stage of the tumor(OR=7.948;95%CI:1.379-45.814;P=0.020),exon 19 deletion mutation as initial EGFR mutation status(OR=3.420;95%CI:1.551-7.544;P=0.002),with air bronchogram(OR=2.545;95%CI:1.103～5.869;P=0.028),with pleural tag(OR=3.036;95%CI:1.259～7.319;P=0.013)and the high expression of CYFRA21-1(OR=2.214;95%CI:1.018-4.818;P=0.045)was the positive predictor of T790M mutation.ConclusionIt is feasible to combine CT signs,tumor markers with clinical characteristics to identify the dominant population of T790M mutation in patients diagnosed as advanced lung adenocarcinoma after the failure of first-generation or second-generation EGFR-TKIs therapy.The stage of the tumor,initial EGFR mutation type,primary lesion with air bronchogram and the presence of a pleural tag and high expression of CYFRA21-1 were independent risk factors for T790M mutation.In practice,when rebiopsy we may encounter insufficient specimen,failed biopsy or negative blood test.According to these characteristics,we can advise patients who are suspected of T790M mutation to repeat the biopsy,so as not to miss the diagnosis of T790M mutation and delay the treatment.