东西方肝癌的分析比较课件

1Comparative Analyses of Hepatocellular Carcinoma between East and West Implication on the design of clinical trials 11th CSCO,Shanghai,2008Ann-Ann-LiiLii Cheng M.D.,Ph.D.Cheng M.D.,Ph.D.Department of Oncology and Department of Internal Medicine,National Taiwan University Hospital;Taipei,Taiwan.Geographic and ethnic factors become important in the era of molecular targeted therapy for cancersAsian(n=342)Non-Asian(n=1350)Proportion survivingTime(months)0.01.00.80.60.40.20246810 12 14 160246810 12 14 16GefitinibPlaceboImportance of Ethnicity for MTA the lessons of ISEL trialEGFR mutation rates in each subgroupStudyCentreNo.of patientsAdenoCa(+BAC)(%)M(%)F(%)Smokers(%)n-smokers(%)Taiwan1NTUH624925612956Taiwan2VGH-T3767.452724469Korea3Seoul NU90219331326Japan4NCC Tokyo666153693568Japan5Aichi CCH596444704271HK6Chinese U7232China7Pek UMCH7648.632.334.8Italy8*U Chieti375106307251.Shih et al,IJC 20052.Chou et al,CCR 20053.Han et al,JCO 20054.Takano et al,JCO 2005*only AdenoCa5.Mitsudomi et al,JCO 20056.Lung et al,PAACR 20057.Mu et al,CCR 20058.Machetti et al,JCO 2005 Liver Cancer in the World Ferlay J et al.IARC Press,2001.Men(396,364)/Women(165,972)North America(%)2.07/2.61Central&South America(%)2.09/4.33Africa(%)6.90/8.69Europe(%)8.21/10.45Asia(%)81.54/74.13Oceania(%)0.25/0.27Geographic differences in the results of clinical trials for advanced HCCSorafenibMedian:46.3 weeks(10.7 mo)(95%CI:40.9,57.9)Survival ProbabilityWeeksHazard ratio(S/P):0.69(95%CI:0.55,0.88)P=0.00058*PlaceboMedian:34.4 weeks(7.9 mo)(95%CI:29.4,39.4)1.0000.750.500.250808162432404856647202742412051611086738120Patients at risk Sorafenib:027622417912678472572Placebo:299303Phase III SHARP TrialOverall survival(Intention-to-treat)Llovet J et al,N Engl J Med.2008 Jul 24;359(4):378-90 (7.9 mo)Comparison of Tx(-)Control ArmsPt NoMedianOSPVTTNMStage IVOkudaStage IIIECOGIII/IVSpain10217M23.5%54.9%0%*0%*HK1063M60.0%90.6%14%13%*Spanish trials excluded“End-stage disease”Llovet JM,Hepatology 1999;29:62-7Yeung YP,Am J Gastroenterol 2005;100:1995-2004EAST VS WESTRandomized trials-octreotide vs placebo Study Schema of SHARP and AP StudiesSorafenib400 mg bidPlaceboEligibility Advanced HCCECOG 0-2Child-Pugh ANo prior systemic therapyStratification Macroscopic vascular invasion(portal vein)and/or extrahepatic spreadECOG PSGeographic areaRANDOMIZEPhase III SHARP and Asia-Pacific Overall SurvivalSorafenibMedian:10.7 months(95%CI:40.9,57.9)Survival ProbabilityMonthsHazard ratio(sor/pla):0.69(95%CI:0.55,0.87)P=0.00058*PlaceboMedian:7.9 months(95%CI:29.4,39.4)1.0000.750.500.25020246810 12 14 16 18Survival ProbabilitySorafenibMedian:6.5 months(95%CI:5.6-7.6)PlaceboMedian:4.2 months(95%CI:3.7-5.5)HR(S/P):0.68 95%CI:0.50-0.93P=0.0140.250.500.751.0000Months248 10 12 14 1620 22618Llovet JM,et al.N Engl J Med 2008:359:378-90 Cheng AL,et al.ASCO 2008,Abstract 4509.SHARPAsia-PacificAsia-Pacific Liver Cancer Study vs SHARP:Baseline Patient CharacteristicsAsia-Pacific(N=226)SHARP1(N=602)Median age(range),years51(23-86)67(21-89)Hepatitis virus status(HBV/HCV),%73/818/28Sex(Male),%8587ECOG PS(0/1/2),%26/69/554/38/8Macroscopic vascular invasion,%3538Extrahepatic spread,%6951BCLC Stage(B/C),%4/9617/82No.of tumor sites,%11144 23531 32012 43513Sites of disease,%Lung5021Lymph node32261 Llovet J,et al.N Engl J Med 2008:359:378-90.Llovet JM et al.Lancet.2003;362:1907-1917.End StageAdvanced StageIntermediate StageEarly StageSurgical TreatmentsLocal AblationNew AgentsTACEHCC(30%)Potentially curative treatments5-yr survival:50-70%(50-60%)Randomized trialsmedian survival if untreated:6-16 mo(10%)BSC survival 2 or Child CPVT(-)PVT(+)Single2 or 3,3 cm4,3 cmICG good*ICG bad*ResectionAblation,Transplan-tationTACEMain PV(-),extra-hepatic spread(-)Main PV(+)or extra-hepatic spread(+)TACEBSCNew agentsBSCBil.2 mg/dlBil.2 mg/dlBil.2 mg/dlBil.2 mg/dlEarly stage(single or 3 nodules 3 cm,PS 0)Intermediate stage(multi-nodular,PS 0)Advanced stage(portal invasion,N1,M1,PS 1-2Terminal stage(PS 2,Child C)NTUH practiceBCLC guidelineResectionAblation,Transplan-tationTACENew agentsBSCSingle,PH(-)Multiple,PH(+)Makuuchi M.et al,Hepatology Research 2007Japan GuidelineEmbolization hepatic arterial infusion chemotherapyGeographic differences in the etiology of HCC implication in the development of MTAsEtiology of HCC Distinct Geographic Distribution Risk FactorsHepatitis B virusHepatitis C virusAlcoholTobaccoOral contraceptivesAflatoxinOther and emerging risk factors/cofactors Estimate Range 22 4-58 60 1272 45 857 12 014 -1050 Limited exposure 5 -Estimate Range 20 18-44 63 4894 20 1533 40 951 -Limited exposure -Estimate Range 60 4090 20 956 -1141 22 -8 -Important exposure 5 -Bosch FX et al.Gastroenterology 2004;127:S5-16.Europe and United States(%)Japan(%)Asia and Africa(%)Is HBV-related HCC a more aggressive tumor?Is HBV-related HCC associated with molecular changes which affect molecular therapy?HBV-related HCCHCC East vs WestLong-term results after surgical treatment were similar in West and East when clinicopa