| Objective:we evaluated the sensitivity,specificity and concordance of a novel ARMS-based assay,namely ARMS-Plus and ddPCR.And we investigated the association of EGFR mutation status in blood with clinical responses to EGFR-TKIs.Meanwhile the clinical value of dynamic monitoring technology and mutation quantitative technique of ARMS-plus were assessed.Ultinately,we evaluated the detection efficiency of the two testing methods in blood comprehensively.Methods:A total of 122 newly-diagnosed,treatment-na?ve advanced NSCLC patients who have used tissues for EGFR testing were enrolled in this study perspectively.We used matched blood samples for EGFR mutation testing by ddPCR and ARMS-plus.Then We use sensitivity,specificity and concordance to analyze the efficiency of EGFR mutation in blood.Then we completed the follow-up with their response to EGFR-TKIs and monitored the patients dynamically.Results:1.A total of 122 newly-diagnosed,treatment-na?ve advanced NSCLC patients were enrolled in this study.Inclusion Patient demographics include :57 patients were female and 65 were male;The median age is 59(30-85);stage ?a,?b to ?NSCLC patients were 7,36 and 79,respectively;115 cases with PS score were 0-2 and 7 cases were3-4.During this study,44 mutation-positive tissue samples included 28 with 19 Del,15with L858 R and 1 with 19 del and L858 R.2.For the 116 patients with blood samples analyzed by ARMS-Plus,the overall sensitivity and specificity were 77.27%(34/44)and 97.22%(70/72).Detection sensitivity for 19 del and L858 R were 79.31%(23/29)and 68.75%(11/16)and the corresponding specificity for 19 del and L858 R were 98.85%(86/87)and 99.00%(99/100),respectively.The concordance rate of the EGFR mutations detected in tissue and blood specimens was89.66%(104/116);3.For the 77 patients with blood samples analyzed by ddPCR,the sensitivity and specificity for EGFR mutation testing by ddPCR were 72.00%(18/25)and 100%(52/52).The overall concordance rate between blood and tissue genotyping was 90.91%(70/77);4.Blood samples from 71 patients were tested by both ARMS-Plus and ddPCR.The sensitivity,specificity,and concordance rate for ARMS-Plus were 83.33%(20/24),100%(47/47)and 94.37%(67/71),respectively.While,the sensitivity,specificity,and concordance rate for ddPCR were 70.83%(17/24),100%(47/47)and 90.14%(64/71),respectively.The concordance rate between the two blood testing platforms was 92.96%(66/71);5.44 TKI-na?ve patients with positive EGFR activating mutations in tumor tissues were divided into two subgroups:T+P+ and T+P-.The objective response rates(ORR)were 44.1%(15/34)and 30.0%(3/10)for the T+P+ group and T+P-group,respectively.While the disease control rates(DCR)of the two groups were 94.1%(32/34)and90.0%,(9/10).No significant difference in both ORR and DCR was observed between the two groups(P=0.49 and P=0.55);6.we compared the wild-type EGFR allele concentration between T+P+ and T+Pgroups.The median total plasma wild-type EGFR allele concentration was 3676.8/m L and2098.0/mL for T+P+ and T+P-groups,respectively.No significant difference was observed between the two groups(P=0.1).Meanwhile,we found that the sensitivity of ARMS-Plus for testing EGFR activating mutations increased with the number of metastatic sites(P=0.01).Conclusion:ARMS-Plus and ddPCR could become effective methods for EGFR mutation testing for advanced NSCLC in blood.But ARMS-Plus got higher efficiency and clinical value.. |
PDF Full Text Request