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1、晚期非小細(xì)胞肺癌內(nèi)科治療的個體化同濟(jì)大學(xué)附屬上海市肺科醫(yī)院周彩存晚期非小細(xì)胞肺癌的治療現(xiàn)狀Platinum-baseddoubletsimproveoverallsurvivalProlongedchemotherapymorethan3-4cyclescouldnotfurtherimproveefficacyDoubletsplusavastinorcetuximabimproveoverallsurvivalcomparedwithdoubletsChemotherapycouldimpr
2、ovedisease-relatedsymptomsChemotherapyhastoxicitiesAdvancedlungcancercouldnotbecuredandouraimistomakeitchronicdisease個體化治療Definition-4R:Rightagent,rightdose,rightpatientsandrighttiming-Biomarkers：predictive,prognostic-Purpose:improvementofefficacyoft
3、herapyAdvantages？-Informativetreatmentstrategy-Bettertreatmentoutcome-Lessriskoftoxicities-Decreaseincost我院開展的晚期NSCLC藥物基因組學(xué)個體化研究ERCC1RRM1BRCA1SNPofDNArepairgenesERCC1和XRCC3基因多態(tài)性在晚期接受含鉑方案化療病人中的療效預(yù)測作用PublishedinJJCO研究方案及流程2005.9月to2007.6月IIIB/IV期NSCLCC
4、hemo-na?ve重要臟器功能正常無腦轉(zhuǎn)移，脊髓壓迫檢測外周血白細(xì)胞ERCC1118和XRCC3241單核苷酸多態(tài)性NP(N=53)GP(N=46)TP(N=31)DCR85.4%PR20%SD65.4%PD14.6%1線化療方案N=130Taqman探針Taqman探針結(jié)合實時熒光PCR方法與直接測序法一致Figure1Real-timePCRreactioncurvesandsequencingprofileofERCC1codon118(A)homozygouswidegenotype.
5、(B)heterozygousgenotype.(C)homozygousvariantgenotypeFigure2Real-timePCRreactioncurvesandsequencingprofileofXRCC3coden241(A)homozygouswidegenotype.(B)heterozygousgenotype.(C)homozygousvariantgenotypeERCC1118XRCC3241基線特征及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例患者進(jìn)入本研究SNP與化療療效的關(guān)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者能明顯從鉑類治療中生存獲益17.5mvs13.5m，p=0.00315
8、mvs15.5m，p=0.57多因素回歸分析ERCC1mRNA表達(dá)水平對NSCLC一線接受含鉑雙藥治療的療效預(yù)測作用2006.11月to2008.11月IIIB/IV期NSCLCChemo-na?ve重要臟器功能正常無腦轉(zhuǎn)移，脊髓壓迫化療前通過FOB,穿刺，活檢等方法獲取腫瘤標(biāo)本檢測ERCC1mRNA的表達(dá)NP(N=43)GP(N=23)TP(N=24)DCR80.6%PR39.8%PD19.4%1線化療方案N=100AcceptedbyTaqman探針患者基線特征ItemsN年齡<70y/>7
