肝癌综合治疗.ppt
肝癌的综合治疗肝癌的综合治疗Multidisciplinary Strategies to Management of HCC背景背景 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的的BCLC分期系统和治疗推荐分期系统和治疗推荐Liver transplantPEI/RFCurative treatmentsTACEHCCSingleIncreasedAssociateddiseasesNormalNoYesNoYesTerminalstagePST 0-2,Child-Pugh A-BMultinodular,PST 0 Portal invasion,N1,M1SorafenibPortal pressure/bilirubin3 nodules 3 cmIntermediate stagePST 2,Child-Pugh CVery early stageSingle 2,Child-Pugh CVery early stageSingle 5cm)TACE(5cm)TACE(5cm)Recurrence curvesPatients with high risk factors for residual tumor进展期肝癌进展期肝癌Staging Strategy and Treatment for Patients With HCCLiver transplantPEI/RFCurative treatmentsTACEHCCSingleIncreasedAssociateddiseasesNormalNoYesNoYesTerminalstagePST 0-2,Child-Pugh A-BMultinodular,PST 0 Portal invasion,N1,M1SorafenibPortal pressure/bilirubin3 nodules 3 cmIntermediate stagePST 2,Child-Pugh CVery early stageSingle 2 cmEarly stageSingle or 3 nodules 3 cm,PST 0Advanced stagePortal invasion,N1,M1,PST 1-2PST 0,Child-Pugh AResectionSymptomatic(unless LT)Llovet JM,et al.J Natl Cancer Inst.2008;100:698-711.Bruix J,et al.Hepatology.2005;42:1208-1236.RCTs(50%)Median survival:11-20 mosApproved&Investigational Noncurative Agents for Unresectable HCC AASLD 2005 recommendations Chemoembolization(TACE)(with doxorubicin,cisplatin,or mitomycin)is recommended as first-line,noncurative therapy for nonsurgical patients with large/multifocal HCC who do not have vascular invasion or extrahepatic spread(and are not eligible for percutaneous ablation)(level I)Tamoxifen,octreotide,antiandrogens,and hepatic artery ligation/embolization are not recommended(level I);other options such as drug-eluting beads,radiolabelled yttrium glass beads,radiolabelled lipiodol,or immunotherapy cannot be recommended as standard therapy for advanced HCC outside clinical trialsBruix J,et al.Hepatology.2005;42:1208-1236.TACEIntra-arterial Locoregional Therapy Established TACE Radioembolization:yttrium-90 radioactive microspheres Undergoing clinical trials Drug-eluting beadsPrimary Treatment Modality Used in KoreaTACE 48.2%RFA1.5%Surgery 11.2%Chemotherapy7.5%Radiotherapy2.1%Conservative treatment 29.5%N=1078Joong-Won Park,MD,National Cancer Center.Adapted with permission.Chemoembolization:Randomized Trials(Nearly Identical Techniques)TechniqueSurvival,%Year 1Year 2Year 3TACE573126Supportive care32113TechniqueSurvival,%Year 1Year 2TACE8263Supportive care6327Llovet et al2:N=112 with unresectable HCC,80%to 90%HCV positive,5-cm tumors(70%multifocal)Lo et al1:N=80 with newly diagnosed unresectable HCC,80%HBV positive,7-cm tumors(60%multifocal)1.Lo CM,et al.Hepatology.2002;35:1164-1171.2.Llovet JM,et al.Lancet.2002;359:1734-1739.Chemoembolization:Predictors of SurvivalLo et al1Absence of presenting symptoms(ECOG PS 5 cm)Okuda stage(I vs II)Llovet et al2Absence of constitutional syndrome(ECOG PS 6 months)1.Lo CM,et al.Hepatology.2002;35:1164-1171.2.Llovet JM,et al.Lancet.2002;359:1734-1739.Largest Prospective Study of TACE for Unresectable HCC to Date N=8510 patientsPrimary endpoint:OSMultivariate analysis conducted of factors affecting survivalOSYear 1:82%;Year 3:47%;Year 5:26%;Year 7:16%OS better with lesser degree of liver damageFactors affecting survivalChild-Pugh stageTNM stage(OS better with stage I,increasingly worse progressing toward stage IV)Alpha-fetoprotein levelTakayasu K,et al.Gastroenterology.2006;131:461-469.TACE vs Surgical Resection:A Case-Control Prospective StudyTechniqueSurvival,%Year 1Year 2Year 3Year 5TACE96805630Surgical resection90807052N=182,70%HBV positive,99%Okuda stage I,76%with tumors 3 cm and/or CLIP stage 1-2,5-year survival identical for both groups(27%)Median OS(P=.1529)Resection:65.1 months TACE:50.4 monthsLee HS,et al.J Clin Oncol.2002;20:4459-4465.Chemoembolization:Efficacy Before Transplantation Major issue:dropout rate(20%)Lower in US since adoption of MELD criteria Role of TACE Control tumor and prevent progression Should be considered if waiting time 6 months Complications from TACE:rare(no increased rate of hepatic artery complications)Richard HM 3rd,et al.Radiology.2000;214:775-779.Graziadei IW,et al.Liver Transpl.2003;9:557-563.Alba E,et al.Am J Roentgenol.2008;190:1341-1348.Can TACE Be Used as a Determinant of Tumor Biology?96 consecutive patients treated with TACE 62 exceeded Milan criteria 34 meeting Milan criteria listed immediately 50 patients transplanted 27 exceeded Milan criteriaOtto G,et al.Liver Transpl.2006;12:1260-1267.FunctionalDecompensation(n=1)Patients with HCC;age 65 years without contraindication against LT(n=96)Milan criteria fulfilled(n=34)ListingTACEMilan criteria exceeded(n=62)6 weeks6 weeks6 weeksTACEListing(n=34)WL(n=4)WL (n=1)Progress(n=6)Functionaldecompensation(n=5)Functionaldecompensation (n=1)Extrahepaticdisease(n=5)Stable18 Progress*927 LTStable21 Progress 223 LTTACERegressStable or progress (n=23)RestagingOtto G,et al.Liver Transpl.2006;12:1260-1267
