肝癌綜合治療資料

1、1會計(jì)學(xué)肝癌綜合治療資料肝癌綜合治療資料第1頁/共101頁Liver transplant PEI/RFCurative treatmentsTACEHCCSingleIncreasedAssociateddiseasesNormalNoYesNoYesTerminalstagePST 0-2, Child-Pugh A-BMultinodular, PST 0 Portal invasion, N1, M1SorafenibPortal pressure/bilirubin3 nodules 3 cmIntermediate stagePST 2, Child-Pugh CVery earl

2、y stageSingle 2, Child-Pugh CVery early stageSingle 5cm)TACE(5cm)TACE(5cm)Recurrence curvesPatients with high risk factors for residual tumor第25頁/共101頁第26頁/共101頁Liver transplant PEI/RFCurative treatmentsTACEHCCSingleIncreasedAssociateddiseasesNormalNoYesNoYesTerminalstagePST 0-2, Child-Pugh A-BMulti

3、nodular, 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, e

4、t al. J Natl Cancer Inst. 2019;100:698-711.Bruix J, et al. Hepatology. 2019;42:1208-1236.RCTs (50%) Median survival: 11-20 mos第27頁/共101頁recommended as standard therapy for advanced HCC outside clinical trialsBruix J, et al. Hepatology. 2019;42:1208-1236.第28頁/共101頁第29頁/共101頁第30頁/共101頁TACE 48.2%RFA1.5

5、%Surgery 11.2%Chemotherapy7.5%Radiotherapy2.1%Conservative treatment 29.5%N = 1078Joong-Won Park, MD, National Cancer Center. Adapted with permission. 第31頁/共101頁TechniqueSurvival, %Year 1Year 2Year 3TACE573126Supportive care32113TechniqueSurvival, %Year 1Year 2TACE8263Supportive care6327Llovet et al

6、2: 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. 2019;35:1164-1171.2. Llovet JM, et al. Lancet. 2019;359:1734-1739.第32頁/共101頁1. L

7、o CM, et al. Hepatology. 2019;35:1164-1171.2. Llovet JM, et al. Lancet. 2019;359:1734-1739.第33頁/共101頁Takayasu K, et al. Gastroenterology. 2019;131:461-469.第34頁/共101頁TechniqueSurvival, %Year 1Year 2Year 3Year 5TACE96805630Surgical resection90807052N = 182, 70% HBV positive, 99% Okuda stage I, 76% wit

8、h 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. 2019;20:4459-4465.第35頁/共101頁Richard HM 3rd, et al. Radiology. 2000;214:775-779.Graziadei IW, et al. Liver Transpl. 2019;9:55

9、7-563.Alba E, et al. Am J Roentgenol. 2019;190:1341-1348.第36頁/共101頁Otto G, et al. Liver Transpl. 2019;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

10、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)Restaging第37頁/共101頁Otto G, et al. Liver Transpl.

11、 2019;12:1260-1267.TransplantedAll patientsTACE nonrespondersSurvival00.20.40.60.81.00365 730 109514601825Days80.9%51.9%0%第38頁/共101頁TACE nonrespondersTACE respondersOtto G, et al. Liver Transpl. 2019;12:1260-1267.0Freedom From Recurrence00.20.40.60.81.0365 730 1095 1460 1825Days35.4%94.5%P = .0017第3

12、9頁/共101頁第40頁/共101頁Georgiades CS, et al. J Vasc Interv Radiol. 2019;16:1653-1659. 第41頁/共101頁Murthy R, et al. Biomed Imaging Interv J. 2019;3:e43. 第42頁/共101頁OutcomeDancey et al1(N = 20)Carr et al2(N = 65)Geschwind et al3(N = 80)Salem et al4(N = 43)Response rate, %3947Median survival378 days( 104 Gy) O

13、kuda stage I 649 days628 days24.4 mos Okuda stage II302 days384 days12.5 mos1. Dancey JE, et al. J Nucl Med. 2000;41:1673-1681.2. Carr BI. Liver Transpl. 2019;10(2 suppl 1):S107-S110.3. Geschwind JF, et al. Gastroenterology. 2019;127(5 suppl 1):S194-S205.4. Salem R, et al. J Vasc Interv Radiol. 2019

14、;16:1627-1639.第43頁/共101頁Kulik LM, et al. Hepatology. 2019;47:5-7. 第44頁/共101頁第45頁/共101頁nMedian follow-up: 28monthsVarela M, et al. J Hepatol. 2019;46:474-481.Doxorubicin at Serum (ng/mL)Doxorubicin at Serum (ng/mL)DEB-TACEConventional TACETime PostprocedureTime Postprocedure02004006008001000020040060

15、08001000BL5 mins20 mins40 mins60 mins2 hrs6 hrs24 hrs48 hrs7 daysBL5 mins20 mins40 mins60 mins2 hrs6 hrs24 hrs48 hrs7 days第46頁/共101頁Courtesy Jean-Francois Geschwind, MD. 第47頁/共101頁P(yáng)osttreatment 1: Residual Viable TumorPretreatmentCourtesy Jean-Francois Geschwind, MD. 第48頁/共101頁Courtesy Jean-Francois

16、 Geschwind, MD. 第49頁/共101頁 Underwent successful resection Tumor free 16 months after initial treatmentCourtesy Jean-Francois Geschwind, MD. 第50頁/共101頁第51頁/共101頁第52頁/共101頁第53頁/共101頁第54頁/共101頁第55頁/共101頁第56頁/共101頁第57頁/共101頁第58頁/共101頁第59頁/共101頁第60頁/共101頁第61頁/共101頁第62頁/共101頁第63頁/共101頁1. Bruix J, et al. H

17、epatology. 2019;42:1208-1236.2. Llovet JM, et al. J Hepatol. 2019;48:S20-S37.3. Llovet J, et al. ASCO 2019. Abstract LBA 1.4. Llovet J, et al. N Engl J Med. 2019;359:378-390.第64頁/共101頁第65頁/共101頁第66頁/共101頁TreatmentBenefitEvidenceSurgical treatmentsResectionIncreased survivalCase series Adjuvant thera

18、piesUncertainRandomized trial, meta-analysis, nonblindedLiver transplantationIncreased survivalCase series Neoadjuvant therapiesTreatment responseNonrandomized trialsLocoregional treatmentPercutaneous treatmentIncreased survivalCase seriesRFA vs PEIBetter local controlRandomized trial, meta-analysis

19、, nonblindedChemoembolizationIncreased survivalRandomized trial, meta-analysis, nonblindedArterial chemotherapyTreatment responseCase seriesInternal radiationTreatment responseCase seriesLlovet JM, et al. J Natl Cancer Inst. 2019;100:698-711. 第67頁/共101頁TreatmentBenefitEvidenceSystemic therapiesSoraf

20、enib Increased survivalRandomized trial, meta-analysis, double blindedTamoxifenNo benefitRandomized trial, meta-analysis, double blindedChemotherapyNo benefitRandomized trial, meta-analysis, nonblindedIFNNo benefitRandomized trial, meta-analysis, nonblindedLlovet JM, et al. J Natl Cancer Inst. 2019;

21、100:698-711. 第68頁/共101頁第69頁/共101頁Roberts LR, et al. Semin Liver Dis. 2019;25:212-225. 第70頁/共101頁第71頁/共101頁Llovet JM, et al. N Engl J Med. 2019;359:378-390.第72頁/共101頁226 discontinued sorafenib86 had an adverse event61 had radiologic and systematic progression28 withdrew consent 1 had ECOG score of 4

22、3 died47 had other reason297 received sorafenib(safety population)71 included in the ongoing study1 had an adverse event1 had a protocol violation299 were assigned to receive sorafenib(intent-to-treat population)602 underwent randomization902 patients were screened300 were excluded244 had protocol e

23、xclusion criteria 24 withdrew consent 15 had an adverse event 11 died 6 were lost to follow-up303 were assigned to receive placebo(intent-to-treat population)1 had a protocol violation302 received placebo(safety population)242 discontinued placebo90 had an adverse event62 had radiologic and systemat

24、ic progression25 withdrew consent 7 had ECOG score of 4 6 died52 had other reason60 included in the ongoing studyLlovet JM, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2019;359:378-390. 2019, Massachusetts Medical Society. All rights reserved.第73頁/共101頁CharacteristicSorafeni

25、b(n = 299)Placebo(n = 303)Median age, yrs64.966.3Male, %8787BCLC stage, % B (intermediate)1817 C (advanced)8283Vascular invasion, %7070Llovet JM, et al. N Engl J Med. 2019;359:378-390.第74頁/共101頁Llovet JM, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2019;359:378-390. 2019, Ma

26、ssachusetts Medical Society. All rights reserved.Median OSSorafenib: 10.7 mosPlacebo: 7.9 mosMedian TTSPSorafenib: 4.1 mosPlacebo: 4.9 mosMedian TTRPSorafenib: 5.5 mosPlacebo: 2.8 mosMonths Since RandomizationProbability of Survival0.000.250.500.751.000 1 2 3 4 5 6 7 8 91011121314 151617P .001A OSMo

27、nths Since RandomizationProbability of No Symptomatic Progression0 1 2 3 4 5 6 7 8 9101112 1314 151617P - 0.77B Time to Symptomatic Progression180.000.250.500.751.00Months Since RandomizationProbability of Radiologic Progression01 23456789 1011PlaceboSorafenibP 0.001C Time to Radiologic Progression0

28、.000.250.500.751.0012第75頁/共101頁Llovet JM, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2019;359:378-390. 2019, Massachusetts Medical Society. All rights reserved.0.00.51.01.5Sorafenib BetterPlaceboBetterSubgroupECOG score 0 1-2Extrahepatic spread No YesMacroscopic vascular in

29、vasion No YesMacroscopic vascular invasion,extrahepatic spread, or both No YesHazard Ratio (95% CI)00.68 (0.50-0.95)0.71 (0.52-0.96)0.55 (0.39-0.77)0.85 (0.64-1.14)0.74 (0.54-1.00)0.68 (0.49-0.93)0.52 (0.32-0.85)0.77 (0.60-0.99)第76頁/共101頁Llovet JM, et al. Sorafenib in advanced hepatocellular carcino

30、ma. N Engl J Med. 2019;359:378-390. 2019, Massachusetts Medical Society. All rights reserved.AEs, %Sorafenib (N = 297)Placebo (N = 302)P ValueAny GradeGrade 3Grade 4Any GradeGrade 3Grade 4Any GradeGrade 3 or 4Overall incidence8052Constitutional symptomsFatigue2231163 1.071.00Weight Loss920100 .001.0

31、3Dermatologic eventsAlopecia1400200 .001NADry skin800400.04NAHand-foot skin reaction21803 10 .001 .001Pruritus8007 10.651.00Rash or desquamation16101100.12.12Other510100 .001.12第77頁/共101頁AEs, %Sorafenib (N = 297)Placebo (N = 302)P ValueAny GradeGrade 3Grade 4Any GradeGrade 3Grade 4Any GradeGrade 3 o

32、r 4Gastrointestinal eventsAnorexia14 10310 .0011.0Diarrhea39801120 .001 .001Nausea11 10810.16.62Vomiting510310.14.68Voice changes600100 .001NAHypertension520210.05.28Liver dysfunction 1 10000.50.50Abdominal pain not otherwise specified820310.007.17Bleeding71041 1.071.00Llovet JM, et al. Sorafenib in

33、 advanced hepatocellular carcinoma. N Engl J Med. 2019;359:378-390. 2019, Massachusetts Medical Society. All rights reserved.第78頁/共101頁Scheithauer W, et al. Oncology (Williston Park) 2019; 18:1161.第79頁/共101頁第80頁/共101頁Grade Symptom1 Minimal skin changes or dermatitis (eg, erythema) without pain2 Skin changes (eg, peeling, blisters, bleeding, edema) or pain, not interfering with function3 Skin changes with pa