2019年肝癌综合治疗.ppt

肝癌的综合治疗MultidisciplinaryStrategiestoManagementofHCC复旦大学肝癌研究所背景绝大多数（80-90％）的HCC合并肝硬化HCC治疗策略应考虑对肿瘤作用，并避免肝功能损害HCC的分期系统也应同时考虑肿瘤因素，和肝功能损害的严重性至今尚未有公认的HCC的分期系统肝癌的BCLC分期系统目前在西方国家应用较广，对治疗有指导意义。HCC的BCLC分期系统和治疗推荐LivertransplantPEI/RFCurativetreatmentsTACEHCCSingleIncreasedAssociateddiseasesNormalNoYesNoYesTerminalstagePST0-2,Child-PughA-BMultinodular,PST0Portalinvasion,N1,M1SorafenibPortalpressure/bilirubin3nodules≤3cmIntermediatestagePST2,Child-PughCVeryearlystageSingle2cmEarlystageSingleor3nodules≤3cm,PST0AdvancedstagePortalinvasion,N1,M1,PST1-2PST0,Child-PughAResectionSymptomatic(unlessLT)LlovetJM,etal.JNatlCancerInst.2008;100:698-711.BruixJ,etal.Hepatology.2005;42:1208-1236.Surgicaltreatments:applicableoverallto30%ofHCCatfirstdiagnosisand2%to5%ofrecurrentHCCHCC的BCLC分期系统和治疗LivertransplantPEI/RFTACEHCCSingleIncreasedAssociateddiseasesNormalNoYesNoYesTerminalstagePST0-2,Child-PughA-BMultinodular,PST0Portalinvasion,N1,M1SorafenibPortalpressure/bilirubin3nodules≤3cmIntermediatestagePST2,Child-PughCVeryearlystageSingle2cmEarlystageSingleor3nodules≤3cm,PST0AdvancedstagePortalinvasion,N1,M1,PST1-2PST0,Child-PughAResectionSymptomatic(unlessLT)20%Nonsurgicaltreatments:applicableoverallto50%ofHCCatfirstdiagnosisand50%to70%ofrecurrentHCC治疗的目的肿瘤缩小改善生命质量延长生存QALYHCC治疗选择早期HCC–外科切除（肝部分切除）–肝移植–经皮毁损（PEI，RFA，HIFU，冷冻，微波）进展期HCC–TACE–系统治疗（化疗）–新治疗（分子靶向，放疗…）早期肝癌早期HCC的手术切除根治？根治术后5年生存率：50-70％术后5年复发率：60-80％问题：如何达到根治？如何降低复发？Pre-operativeTACE+ResectionDownstagingresection：术后5年生存率≈小肝癌肝动脉插管＋结扎/TACE/Chemotherapy？减小瘤体：手术简单，且控制微小病灶减少血供：手术安全减少术中播散Zhou2009AnnSurg2009;249:195–202Pre-operativeTACERisk：可切除－－不可切除对肝功能差的病人：进一步损害肝功能Japan：RCT结果类似（SasakiA.EurJSurgOncol.2006;32:773–9.）肝移植术后复发（周俭教授）肝源等待：BridgeTreatmentsofHepatocellularCarcinomainCirrhoticPatientsSubmittedtoLiverTransplantation.DigDisSci(2008)53:2830–2831TACE:BridgetoOLTDoesnotimprovelong-termsurvival(gradeC).NoconvincingevidencethatTACEallowstoexpandthecurrentselectioncriteriaforOLT,northatTACEdecreasesdropoutratesonthewaitinglist(gradeC).TACEdoesnotincreasetheriskforpostoperativecomplications(gradeC).ThereisinsufficientevidencethatTACEoffersanybenefitwhenusedpriortoOLT,neitherforearlynorforadvancedHCC.Americanjournaloftransplantation2006;6(11):2644-50.局部毁损小肝癌：媲美于手术切除复发率值得担心小肝癌2.8cmPEIorRFA?PEI3y5yChildA(survival3vs.5y.)79%47%ChildB(survival3vs.5y.)63%29%ChildC(survival3vs.5y.)12%0%AASLD2004:Leoncinietal.(n=104):PEIRFATumordestruction82%98%2-ySurvival96%98%2-yRecurrence32%10%RFvsPEILocalablativetherapiesinHCC:percutaneousethanolinjectionandradiofrequencyablation–RFAissuperiortoPEIfortreatingsmallHCC–survivalafterPEIorRFAincomparisonwithsurgery–TACE+PEI/RFAsurvivalwasimprovedfurther.DigDis.2009;27(2):148-56.RF+PEI操作性的RFvsResection•AnnSurg2006;243:321–328)ChenMS.AnnSurg2006;243:321–328PuzzlePre-TACE+ResectionnousePre-TACE+RFimprovedRF=ResectionRadicalresection＋IFN-aresection+IFNresectionOS:63.8months38.8monthsP=0.0003DFS:31.2months17.7monthsP=0.142SunHC.JCancerResClinOncol2006;132:458-65EvidenceofBenefitinTreatmentofHCCTreatmentBenefitEvidenceSystemictherapiesSorafenibIncreasedsurvivalRandomizedtrial,meta-analysis,doubleblindedTamoxifenNobenefitRandomizedtrial,meta-analysis,doubleblindedChemotherapyNobenefitRandomizedtrial,meta-analysis,nonblindedIFNNobenefitRandomizedtrial,meta-analysis,nonblindedLlovetJM,etal.JNatlCancerInst.2008;100:698-711.PostadjuvantTACE0255075100CumSurvival（%）020406080100SurvivalTime（month）Control（≤5cm）Control（＞5cm）TACE（≤5cm）TACE（＞5cm）SurvivalCurvesPatientswithlowriskfactorsforresidualtumor0255075100CumSurvival（%）020406080SurvivalTime（month）Control（≤5cm）Control（＞5cm）TACE（≤5cm）TACE（＞5cm）P=0.0020SurvivalCurvesPatientswithhighriskfactorsforresidualtumorPostadjuvantTACE0255075100Probabilityorrecurrence（%）020406080100TTR(month)Control(≤5cm)Control(＞5cm)TACE(≤5cm)TACE(＞5cm)RecurrencecurvesPatientswithlowriskfactorsforresidualtumor1000255075Probabilityorrecurrence（%）020406080TTR(month)Control(≤5cm)Control(5cm)TACE(≤5cm)TACE(5cm)RecurrencecurvesPatientswithhighriskfactorsforresidualtumor进展期肝癌StagingStrategyandTreatmentforPatientsWithHCCLivertransplantPEI/RFCurativetreatmentsTACEHCCSingleIncreasedAssociateddiseasesNormalNoYesNoYesTerminalstagePST0-2,Child-PughA-BMultinodular,PST0Portalinvasion,N1,M1SorafenibPortalpressure/bilirubin3nodules≤3cmIntermediatestagePST2,Child-PughCVeryearlystageSingle2cmEarlystageSingleor3nodules≤3cm,PST0AdvancedstagePortalinvasion,N1,M1,PST1-2PST0,Child-PughAResectionSymptomatic(unlessLT)LlovetJM,etal.JNatlCancerInst.2008;100:698-711.BruixJ,etal.Hepatology.2005;42:1208-1236.RCTs(50%)Mediansurvival:11-20mosApproved&InvestigationalNoncurativeAgentsforUnresectableHCCAASLD2005recommendations–Chemoembolization(TACE)(withdoxorubicin,cisplatin,ormitomycin)isrecommendedasfirst-line,noncurativetherapyfornonsurgicalpatientswithlarge/multifocalHCCwhodonothavevascularinvasionorextrahepaticspread(andarenoteligibleforpercutaneousablation)(levelI)–Tamoxifen,octreotide,antiandrogens,andhepaticarteryligation/embolizationaren