肺癌基因突变于化疗疗效分析.pptx

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Ming Sound Tsao,MD,FRCPC,Department of Pathology,Princess Margaret Hospital,Division of Cellular and Molecular Biology,Ontario Cancer Institute,University of Toronto,Molecular Pathology of Lung Cancer,ONTARIO CANCER INSTITUTE(OCI),PRINCESS MARGARET HOSPITAL,Objective:,To report the results of 2 important clinical trials reported at 2023 American Society of Clinical Oncologist,Main message:,Molecular Pathology will soon be an important component of pathological diagnosis in lung cancer,Worlds cancer incidence and cancer deaths,Incidence in thousands(%total),Deaths in thousands(%total),Lung,1,305(12.7%),1,211(17.2%),Colon&rectum,1,045(10.2%),608(6.7%),Breast,1,032(10%),430(6.1%),Stomach,973(9.5%),835(11.9%),Liver,626(6.1%),611(8.7%),1999 WHO Pathological Classification of Lung Cancer,Non-small Cell Lung Cancer,Adenocarcinoma,Squamous cell carcinoma,NSCLC-Survival Rate and Proportion at Presentation vs.Clinical stage,Clinical Stage,Percentage of Patients,5-,year survival rate,I,36%,60%,II,8%,39%,IIIA,10%,23%,IIIB,20%,5%,IV,27%,2 regimens(9),Only single agent in young patient(2),CT or RT given within 2-4 weeks,concurrent CT(5),Biochemical abnormalities(4),Symptomatic CNS metastases(2),BR.21 Patient Characteristics,Erlotinib,(N=488),Placebo,(N=243),Median Age(yrs),62.2,59.5,Gender,Male,65%,66%,Female,35%,34%,ECOG PS(%),0,13%,14%,1,52%,54%,2,26%,23%,3,9%,9%,Histology,Adenocarcinoma,50%,49%,Other,50%,51%,BR.21 Progression Free Survival,*Adjusted for stratification factors,Months,_,Erlotinib,_,Placebo,*HR 0.61,p=0.001,BR.21 Overall,Progression-Free and 1-year Survival,Erlotinib,(N=488),Placebo,(N=243),HR*,Log Rank,P,Progression Free Survival,2.2,m,1.8,m,0.61,0.001,Overall Survival,6.7,m,4.7,m,0.72,0.001,I-year survival,31%,22%,*Adjusted for stratification factors,BR.21 Overall Survival,*Adjusted for stratification factors,_,Erlotinib,_,Placebo *HR 0.72,p=0.001,Months,31%,22%,BR.21,Survival by Smoking History,Months,_,Erlotinib Non-Smoker,_,Placebo Non-Smoker,_,Erlotinib Smoker,_,Placebo Smoker,p=0.03*,*significant difference across the levels of the factor.,BR.21 Summary,This is the,first,placebo controlled randomized trial to confirm that an oral tyrosine（,酪氨酸,）kinase inhibitor of EGFR can prolong survival,Treatment with erlotinib was associated with significantly,longer overall survival,longer progression free survival,improved lung cancer-related symptoms,improved quality of life,Survival significantly better among non-smokers,EGFR Mutations in Lung Cancer:Correlation with Clinical Response to Gefitinib Therapy.,Paez JG,Janne PA,Lee JC,Tracy S,Greulich H,Gabriel S,Herman P,Kaye FJ,Lindeman N,Boggon TJ,Naoki K,Sasaki H,Fujii Y,Eck MJ,Sellers WR,Johnson BE,Meyerson M.,Dana Farber Cancer Institute and Harvard University,Science April 29,2023,Mutations（,突变）(,point mutation and deletions)were detected in exons（,外显子）18,19,and 21 in the kinase domain of EGFR gene.,Mutations were found in:,26%(15/68)of lung cancers from Japan,2%(1/61)of lung cancers from USA,Mutations among Japanese patients:,14/15 were in adenocarcinoma,8/14(57%)women with adenocarcinoma had mutations,Mutations were found in:,all 5 patients who responded to gefitinib(Iressa)treatment at DFCI,none of 4 patients who did not respond to gefitinib treatment,Activating Mutations in the Epidermal Growth Factor Receptor Underlying Responsiveness of Non Small-Cell Lung Cancer to Gefitinib,Thomas J.Lynch,M.D.,Daphne W.Bell,Ph.D.,Raffaella Sordella,Ph.D.,Sarada Gurubhagavatula,M.D.,Ross A.Okimoto,B.S.,Brian W.Brannigan,B.A.,Patricia L.Harris,M.S.,Sara M.Haserlat,B.A.,Jeffrey G.Supko,Ph.D.,Frank G.Haluska,M.D.,Ph.D.,David N.Louis,M.D.,David C.Christiani,M.D.,Jeff Settleman,Ph.D.,and Daniel A.Haber,M.D.,Ph.D.,Massachusetts General Hospital and Harvard Medical School,NEW ENGLAND JOURNAL OF MEDICINE,MAY 20 ISSUE,EGFR mutations were found in:,8 of 9 lung cancer patients who were responsive to treatment with Iressa,0 of 7 lung cancer patients who were non-responsive,All 8 tumors were adenocarcioma,5 of 8 were from women non-smokers,Mutations were,not,found in 95 non-lung cancer tumors,International Association for the Study of Lung Cancer,EGFR Summit Meeting Highlights,July 9-10,2023,Baltimore,USA,There are 18 mutations that have been described in exons 18-23.,Rates of mutations varied according to countries:,Adenocarcinoma in never smokers:,60%in tumors from Taiwan,62%from Japan,30 45%from USA(compared to 2%overall),80%from Hong Kong,Adenocarcinoma of ever smoker from HK:40%,EGFR mutation and Ras mutations are mutually（,相互）,exclusive,排斥,In Korea where women rarely smoke,response to Iressa is seen in up to 60%of patients.,Future studies,What are the best predictors of benefits in patients treated with EGFR TKI?,Mutation alone?,Other gene or protein markers in the tumor or serum,Future improvement in lung cancer diagnosis and treatment will be based on better understanding of the molecular pathology of lung cancer.,Molecular diagnosis will play increasingly important roles in future management of lung cancer patients.,Final Comments,Acknowledgement,Laboratory personnel:,Liu Ni,Zhu Chang-Qi,Davina Lau,Past visiting fellows:,Fiona Blackhall(Manchester),Mu Xiao-yan(Shandong),Lu Ming(Beijing),Dr.Frances Shepherd(Medical oncologist and current President of IASLC),Thoracic surgeons at Toronto General Hospital/Princess Margaret Hospital,National Cancer Institute of Canada Clinical Trial Group and staffs,