晚期非小细胞肺癌内科治疗的个体化ppt课件

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1、晚期非小细胞肺癌内科治疗的个体化同济大学附属上海市肺科医院周彩存晚期非小细胞肺癌的治疗现状Platinum-baseddoubletsimproveoverallsurvivalProlongedchemotherapymorethan3-4cyclescouldnotfurtherimproveefficacyDoubletsplusavastinorcetuximabimproveoverallsurvivalcomparedwithdoubletsChemotherapycouldimpr

2、ovedisease-relatedsymptomsChemotherapyhastoxicitiesAdvancedlungcancercouldnotbecuredandouraimistomakeitchronicdisease个体化治疗Definition-4R:Rightagent,rightdose,rightpatientsandrighttiming-Biomarkers：predictive,prognostic-Purpose:improvementofefficacyoft

3、herapyAdvantages？-Informativetreatmentstrategy-Bettertreatmentoutcome-Lessriskoftoxicities-Decreaseincost我院开展的晚期NSCLC药物基因组学个体化研究ERCC1RRM1BRCA1SNPofDNArepairgenesERCC1和XRCC3基因多态性在晚期接受含铂方案化疗病人中的疗效预测作用PublishedinJJCO研究方案及流程2005.9月to2007.6月IIIB/IV期NSCLCC

4、hemo-naïve重要脏器功能正常无脑转移，脊髓压迫检测外周血白细胞ERCC1118和XRCC3241单核苷酸多态性NP(N=53)GP(N=46)TP(N=31)DCR85.4%PR20%SD65.4%PD14.6%1线化疗方案N=130Taqman探针Taqman探针结合实时荧光PCR方法与直接测序法一致Figure1Real-timePCRreactioncurvesandsequencingprofileofERCC1codon118(A)homozygouswidegenotype.

5、(B)heterozygousgenotype.(C)homozygousvariantgenotypeFigure2Real-timePCRreactioncurvesandsequencingprofileofXRCC3coden241(A)homozygouswidegenotype.(B)heterozygousgenotype.(C)homozygousvariantgenotypeERCC1118XRCC3241基线特征及SNP分布GenotypingMaleFemaleAgeAde

6、noSquamStIIIBStIVTotal56.9%43.1%6162.3%37.7%30.8%69.2%ERCC1118C/C53.6%46.4%6157.1%42.9%28.9%71.1%118C/T+T/T63.0%37%6071.7%28.3%34.8%65.2%XRCC3241C/C56.8%43.2%6159.5%40.5%34.2%65.8%241C/T+T/T52.6%47.4%6078.9%21.1%10.5%89.5%Adeno=adenocarcinoma,Squam=s

7、quamouscellcarcinoma,St=Stage130例患者进入本研究SNP与化疗疗效的关系GenotypingNumberPRSDPDTotal13020%65.4%14.6%ERCC1Wild-type8419%65.5%15.5%Mutant4621.7%65.3%13.0%XRCC3Wild-type11119.8%64%16.2%Mutant1921.1%77.6%5.3%ERCC1118C/TorT/T者能明显从铂类治疗中生存获益17.5mvs13.5m，p=0.00315

8、mvs15.5m，p=0.57多因素回归分析ERCC1mRNA表达水平对NSCLC一线接受含铂双药治疗的疗效预测作用2006.11月to2008.11月IIIB/IV期NSCLCChemo-naïve重要脏器功能正常无脑转移，脊髓压迫化疗前通过FOB,穿刺，活检等方法获取肿瘤标本检测ERCC1mRNA的表达NP(N=43)GP(N=23)TP(N=24)DCR80.6%PR39.8%PD19.4%1线化疗方案N=100AcceptedbyTaqman探针患者基线特征ItemsN年龄<70y/>7