Correlation Between EGFR T790M And Prognosis Of Advanced Lung Adenocarcinoma

Objective: T790M mutation is the main resistance mechanism of epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKI).Serum circulating tumor DNA(ct DNA)is an ideal method to detect T790M mutations.This study aimed to explore the relationship between ct DNA identified EGFR T790M mutation status and EGFR-TKI acquired resistance and prognosis in patients with advanced lung adenocarcinoma(LUAD).Methods: 93 patients with advanced LUAD who acquired resistance with EGFR-TKI in the first-line of Nanjing general hospital from January 2012 to January 2016 were analyzed retrospectively.The ct DNA was extracted from peripheral blood according to the instructions of circulating nucleic acid kit QIAamp(Qiagen,Hilden,Germany)and mutational status of T790M in ct DNA was tested using next generation sequencing(NGS).The relationship between T790M and sex,age,smoking history,clinical stage,histological subtype,ECOG score,initial EGFR mutant type,EGFR-TKI types of drugs,type of progression after EGFR-TKI resistance,level of serum CEA after EGFR-TKI resistance,therapeutic regimen and prognosis were further analyzed.Results: In 93 cases of advanced LUAD patients who were treated with EGFR-TKI in the first-line,T790M mutation was 52.7%(49/93).There was no statistically significant difference between T790M mutation and age,clinical stage,histological subtype,ECOG score,initial EGFR mutant type,EGFR-TKI types of drugs(P>0.05).However,it was related to sex,smoking history,type of progression after EGFR-TKI resistance,level of serum CEA after EGFR-TKI resistance and therapeutic regimen after EGFR-TKI resistance(P<0.05).The cut-off value of serum CEA after EGFR-TKI resistance predicting T790M positive was 90.1ug/L,with sensitivity and specificity was44.9% and 90.9%,respectively.The area under curve was 0.639(95% CI: 0.526-0.752).T790M mutation positive patients had prolonged PFS and OS compared with T790M negative patients(PFS,12.4 months vs 6.2 months,P<0.001;OS,29.5 months vs 18.1months,P<0.001).COX univariate and multivariate regression analysis indicated that T790M mutation positive was PFS(RR: 0.302,95% CI 0.162-0.560;P<0.001)and OS(RR:0.422,95% CI 0.250-0.715;P=0.001)independent influencing factors.Conclusion: T790M mutation was related to sex,smoking history,the level of serum CEA after EGFR-TKI resistance,type of progression after EGFR-TKI resistance,which was an independent influencing factor of PFS and OS.