Study Of Plasma CtDNA Detection In The Treatment Of Advanced Non-small Cell Lung Cancer Patients With EGFR-TKI

Objectives:To analyze the relationship between the EGFR gene mutation status and the clinicopathological features in non-small cell lung cancer by histological samples and to research the clinical efficacy and safety of first-line EGFR-TKI targeted therapy in EGFR-sensitive mutant non-small cell lung cancer.Using ctDNA detection to analyze EGFR gene mutation status and T790M gene expression through EGFR-TKI targeted therapy for drug resistance,and to research the effect of first-line EGFR-TKI targeted therapy on EGFR gene expression in non-small cell lung cancer patients and the application of ctDNA detection of EGFR gene mutation in the treatment of patients with non-small cell lung cancer.Methods:1.With a collection of 117 cases of pathologically diagnosed non-small cell lung cancer in our hospital between October 2010 and May 2017,to analyze the mutation status of EGFR gene in' histological specimens of NSCLC patients and find out the relationship between the results and clinicopathological features;2.Of the 117 patients,64 were eligible for enrollment.They were divided into EGFR-sensitive-TKI-targeting therapy group A(41 cases),EGFR wild-type TKI-targeted combination chemotherapy group B(11 cases),and EGFR wild-type chemotherapy group C(12 cases)according to EGFR gene mutations and treatment options.The CT images were reviewed regularly and followed up until the disease has progressed(PD).Clinical indicators mainly include objective effective rate(ORR),disease control rate(DCR),progression-free survival(PFS).To compare two treatment options to see if there is a statistical difference and to explore the clinical efficacy and safety of first-line EGFR-TKI targeted therapy of first-line EGFR-TKI targeted therapy;3.Take 5mL of peripheral blood sample when the review of CT has showed tumor progression.Using Taq DNase ARMS fluorescent PCR Method,to detect status of EGFR gene mutations in ctDNA and confirm changes of EGFR Mutation and T790M drug resistance Genes after grug resistance in TKI,make a statistical analysis of differences in EGFR gene expression before and after drug resistance in TKI.Results:1.The 117 patients with non-small cell lung cancer included 53 males(45.3%),64 females(54.7%),the average age was 61.5 years old,median age was 61,107 cases of adenocarcinoma,10 cases of squamous cell carcinoma,41 cases with smoking history,76 cases without smoking history;58 cases(49.6%)of EGFR gene mutation,including exon 18 in 5 cases,exon 19 mutations in 32 cases,exon 20 mutations in 2 cases,exon 21 mutations in 22 cases,exon 19 and exon 21 accounted for 93.1%of EGFR mutations.The EGFR gene mutation was correlated with patient's gender(P = 0.020),pathological type(P = 0.001)and smoking history(P = 0.000),but not with age,differentiation degree and clinical stage(P>0.05).2.Among 64 non-small cell lung cancer patients,the ORR and DCR of A,B and C groups were 85.4%,36.4%,41.7%and 92.7%,63.6%66.7%respectively,the difference was statistically significant(P<0.05);the mPFS of the three groups were 10.9 Months,5.0 months,4.6 months.The clinical efficacy of EGFR-TKI in group A was significantly better than that in group B and C,the difference was statistically significant(P<0.05).3.There were 34(82.9%)cases of EGFR gene mutation detected by ctDNA of group A.The types of mutations include:exon 18 mutation in 1 case,exon 19 mutation in 19 cases;exon 20 mutation in 1 case,and exon 21 mutation in 12 cases.T790M gene mutation was found in 17 cases(41.5%).There was a significant difference(P<0.05)on the comparison of EGFR gene mutation before and after treatment in group A and B.Conclusion:The positive rate of EGFR gene mutation is higher in females and adenocarcinoma and no smoking history for NSCLC patients,but there was no significant difference in patient's age,differentiation and clinical stage.EGFR-TKI-treated group had significantly higher ORR and DCR and longer PFS than group of EGFR wild-type.EGFR gene mutation rate appears to reduce or change when TKI treatment appears drug resistance,and T790M gene mutation increased,it may be related to acquired drug resistance;Tissue sample is still the first choice in EGFR test,but ctDNA is a choice for patients of NSCLC who can hardly offer tissue samples.