Clinical Study Of T790M Mutation In Blood Of Non-small Cell Lung Cancer Patients With EGFR-TKI Resistance Using NGS Technology

Objective: To conduct a clinical study of T790 M mutation in blood of non-small cel l lung cancer(NSCLC)patients with EGFR-TKI resistance using NGS technology,and to explore the influence of chemotherapy on T790 M mutation in patients with resista nce to EGFR-TKI.Methods: The T790 M mutation in blood of 97 patients was detected by Ion Torrent NGS platform.The relationship between T790 M mutation and clinical features and ef ficacy in those patients with resistance was analyzed before and after chemotherapy.Results:(1)The EGFR gene mutation rate in the serum of the 97 patients was 53.6% before chemotherapy,among which the mutation rate in the exon 19 was 10.3%,in the exon 21 was 12.4%,of the T190 M was 30.9%,and the EGFR mutation-nega tive rate was 47.7%.Further comparisons showed no statistical differences in the inci dence of T790 M mutation respectively relating to gender,age,smoking status,and T NM staging.However,the mutation rate in locally advanced patients was obviously h igher than that in non-locally advanced patients(p <0.05),of which the difference w as statistically significant.The mutation rate of the patients with new sites of metasta sis was obviously lower than that of the patients without new sites of metastasis(p<0.05),of which the difference was statistically significant.(2)The EGFR gene muta tion rate in the serum of the 97 patients was 47.5% after chemotherapy,among whic h the mutation rate in the exon 19 was 15.5%,in the exon 21 was 16.5%,of the T190 M was 15.5%,and the EGFR mutation-negative rate was 52.5%.Further comparis ons showed no statistical differences in the incidence of T790 M mutation respectively relating to gender,age,smoking status,and TNM staging.However,the mutation ra te in locally advanced patients was obviously higher than that in non-locally advance d patients(p <0.05),of which the difference was statistically significant.The mutatio n rate of the patients with new sites of metastasis was obviously lower than that of the patients without new sites of metastasis(p<0.05),of which the difference was sta tistically significant.(3)After the resistance occurred,the mutation rate of T790 M wa s 30.9% before chemotherapy,and after three cycles of chemotherapy,it was reduced to 15.5%.The difference was statistically significant(p<0.05).The result suggested that the current chemotherapy regimen can reduce the mutation rate of T790 M.A Fur ther analysis showed that the T790 M mutation status in 13 patients was consistent be fore and after chemotherapy.Among other 15 patients,the exon 19 mutation was obs erved in 5 patients,the exon 21 mutation in 4 patients and 6 patients were mutation-negative.Two negative patients' status was changed from EGFR mutation-negative b efore chemotherapy to T790M-positive.(4)After chemotherapy,among the 97 patient s,partial response(PR)was observed in 10 patients,stable condition(SD)in 36 pati ents and progression disease(PD)in 51 patients.According to the therapeutic effect,patients were divided into two groups.The group in which the disease was controlle d(PR+SD)included 46 patients,among whom 6 patients had T790 M mutation(13.0%),while the group having progressive disease included 51 patients,among whom9 patients had T790 M mutation(17.6%).The difference was significant(P <0.05).Th e above result suggested that the T790 M mutation rate may be related to the clinical efficacy of chemotherapy.The disease control rate(DCR)in T790M-negative patient s was 55.6% while in T790M-positive patients was 40.0%,which had no statistical s ignificance.(5)After the follow-up,a significant shortening in the progression-free su rvival(PFS)was found in the patients who were T790M-positive after chemotherapy with only 2.9 ± 0.98 months as compared to the T790M-negative patients with 4.1±1.26 months(p <0.01).The factors that may affect PFS were further studied using uni variate Cox regression analysis and the results showed that patients' gender,age,TN M staging,smoking status,and ECOG Score had no influence on the survival time(p > 0.05),while T790 mutation had a significant influence on it(p < 0.05).T790 M is a risk factor for PFS(RR = 0.786,95% CI: 0.369-1.025,p = 0.042).Conclusion:(1)The occurrence of resistance to EGFR-TKI may be related to the T790 M mutati on.The chemotherapy may have an effect on T790 M mutation in peripheral blood,b ut further studies are needed to explore the specific mechanism.(2)Patients who are T790M-negative before chemotherapy may develop distant metastasis earlier.Patients who are positive after chemotherapy have poor prognoses.(3)Patients who are T790M-positive before chemotherapy have worse prognoses,which is a risk factor for P FS.