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Evaluation Of Target Therapy And Clinical Signification Of EGFR Rare Mutations Detected By Arms In Non-small Cell Lung Cancer

Posted on:2019-12-21Degree:MasterType:Thesis
Country:ChinaCandidate:Y LuFull Text:PDF
GTID:2404330575454380Subject:Oncology
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Background and Objectiv:Nowadays,the incidence rate and mortality rate of malignant tumors in our country or even around the world is still caused by lung cancer,non-small cell lung cancer(NSCLC)accounts for about 85%.Currently,as people continued to deppen studies of lung cancer grnotyping,there is conformed that somatic EGFR mutations is a specific and effective predictor for the response of EGFR-TKI.EGFR mutation happened in Asians reached about 30%-60%,as twice about in Europeans.EGFR mutations exist in 18-21 exons,and the most frepuent mutations and sensitive are 19 exon deletions mutation and L858 R point mutation,except the already known drug resistant mutation 20 exon insertion mutation and 20 exon T790 M mutation,the clinical features and effectiveness to EGFR-TKI are unknown in most uncomon mutations.So this paper analysis clinical characteristics and effectiveness to a part of can be evaluated targeted therapy patients with EGFR uncommon mutations.Thus,these data can provide a certain reference for patients who gets EGFR uncommon mutations in futher clinical therapeutic method.Meterials and Methonds:We continuously take in all the patients who were diagnosed histopathologically NSCLC patients in Tumor Affiliated Hospital of Guangxi Medical University from August 2010 to September 2016.Finally,we enrolled 1862 patients and who have been pathologically confirmed(by solid tissue or not).In these patients,cases are assigned by sex,age,smoke or not,pathological pettern,clinical stages.Then we divided all the 684 patients with EGFR mutation into 630 cases of common mutations and 54 cases of rare mutations.In the end,we acess the correlation and difference between common mutations,rare mutations and EGFR negative patients accoding age,sex,smoking history,clinical stage,pathological types and clinical fentures such as these data.The tragetd therapy response will be observed and analyzed.The clinical stage or origin of specimen and the age were not associated with the occurrence of EGFR mutation.Among the 684 EGFR mutation positive patients,630 cases(320 males and 310 females)were common mutation.accounting for 92.1% of the total mutation.Common mutations include 345 cases of 19 exon deletion mutation,accouting for 55% of common mutations and 18.5% of total mutations.285 cases of 21 exon L858 R point mutation,,accouting for 45% of common mutations and 15.4% of the total mutation.There were 54 cases of rare mutation(24 males and 30 females),the mutation rate was 2.9 percent,,accouting for 7.9 percent of the total mutation.There were 11 patients with already known resistance mutation,and 9 cases(5 males and 4 females)with single resistance mutation of 20 exon and 2 cases of 20 exon T790 M mutation(1 male and 1 female).Results:Among the 1862 patients enrolled in this study,EGFR mutation rate was higher in female than in male patients(48.9% vs 29.5%,P =0.000);EGFR mutation rate was higher in smokers compared with non-smokers patients(59.6% vs 19.8%,P =0.000);Age <60 years old patients with EGFR mutation rate was equal to those aged 60 years or older(36.7% vs 36.7%,P =0.994),but the results has no statistical significance;The incidence of EGFR mutation in patients with adenocarcinoma was higher than that in non-adenocarcinoma patients(42.0% vs 16.4%,P =0.000).The differentiation degree was divided into unclear?low differentiation ?medium or low differentiation ?medium differentiation ?medium or high differentiation ?high differentiation,and the EGFR mutation rate of low differentiation(40.7%)? madium or low differentiation(42.1%)are obviously higher than the differentiation of high(24.7%)or the differentiation of high and medium(29.7%).3.We retrospectively analyzed the clinical date of 54 patients with rare t mutation.7 cases have been treated with EGFR-TKIs(during the therapy wihout chemotherapy or radiotherapy)that also can be evaluated resopnse.6 patients treated with gefitinib and 1 case treated with afatinib.Disease control rates(DCR)was 57%(4/7)among the 7 parients,4 patients got SD.The longest PFS was 12.3 months who got the 19del+20ins,and the shortest was 0.8 month who got the mutation L858R+S768I+L861Q.Conlusions:1.The study get the result that female non-smoker,adenocarcinoma patients are most likely to appear EGFR mutation;2.In rare single mutations,20 exon insertion mutation with the highest mutaion frequence;3.High ECOG score are more likely to have single mutation,which maybe related with the frequence of resisitance mutation by 20 exon insertion in this study,which directly affects the prognosis.4.The responsiveness to EGFR-TKI therapy of the patients who get uncommon mutations were different.
Keywords/Search Tags:NSCLC, adenocarinoma, EGFR, uncommon mutation, resistance, targeted therapy
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