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1、肝癌的综合治疗Multidisciplinary Strategies to Management of HCC,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,Liver transplant,PEI/RF,Curative treatments,TACE,HCC,Single,Increased,Associateddiseas
2、es,Normal,No,Yes,No,Yes,Terminalstage,PST 0-2, Child-Pugh A-B,Multinodular, PST 0,Portal invasion, N1, M1,Sorafenib,Portal pressure/bilirubin,3 nodules 3 cm,Intermediate stage,PST 2, Child-Pugh C,Very early stage,Single 2 cm,Early stage,Single or 3 nodules 3 cm, PST 0,Advanced stage,Portal invasion,
3、N1, M1, PST 1-2,PST 0, Child-Pugh A,Resection,Symptomatic (unless LT),Llovet JM, et al. J Natl Cancer Inst. 2008;100:698-711.Bruix J, et al. Hepatology. 2005;42:1208-1236.,治疗的目的,肿瘤缩小 改善生命质量 延长生存 QALY,HCC 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HC
4、C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-operative TACE + Resection,Downstaging resection：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,Zhou 2009 Ann Surg 2009;249: 195202,Pre-operative TACE,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（Sasaki A.
5、 Eur J Surg Oncol. 2006;32:7739.）,肝移植,术后复发 （周俭教授） 肝源等待：Bridge Treatments of Hepatocellular Carcinoma in Cirrhotic Patients Submitted to Liver Transplantation. Dig Dis Sci (2008) 53:28302831,TACE: Bridge to OLT,Does not improve long-term survival (grade C). No convincing evidence that TACE allows to
6、expand the current selection criteria for OLT, nor that TACE decreases dropout rates on the waiting list (grade C). TACE does not increase the risk for postoperative complications (grade C). There is insufficient evidence that TACE offers any benefit when used prior to OLT, neither for early nor for
7、 advanced HCC.,American journal of transplantation 2006; 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2.8cm,PEI or RFA?,PEI3y5y Child A (survival 3 vs. 5y.)79%47% Child B (survival 3 vs. 5y.) 63%29% Child C (survival 3 vs. 5y.) 12%0%,AASLD 2004: Leoncini et al. (n=104): PEIRFA Tumor destruction82%98%
8、2-y Survival96%98% 2-y Recurrence32%10%,RF vs PEI,Local ablative therapies in HCC: percutaneous ethanol injection and radiofrequency ablation RFA is superior to PEI for treating small HCC survival after PEI or RFA in comparison with surgery TACE+ PEI/RFA survival was improved further.,Dig Dis. 2009;
9、27(2):148-56.,RF+PEI,操作性的,RF vs Resection,Ann Surg 2006;243: 321328),Chen MS. Ann Surg 2006;243: 321328,Puzzle,Pre-TACE +Resection no use Pre-TACE + RF improved RF = Resection,Radical resection IFN-a,resection + IFN resection OS: 63.8 months 38.8 months P=0.0003 DFS: 31.2 months 17.7 months P=0.142,
10、Sun HC. J Cancer Res Clin Oncol 2006; 132:458-65,Evidence of Benefit in Treatment of HCC,Llovet JM, et al. J Natl Cancer Inst. 2008;100:698-711.,Post adjuvant TACE,Post adjuvant TACE,进展期肝癌,Staging Strategy and Treatment for Patients With HCC,Liver transplant,PEI/RF,Curative treatments,TACE,HCC,Singl
11、e,Increased,Associateddiseases,Normal,No,Yes,No,Yes,Terminalstage,PST 0-2, Child-Pugh A-B,Multinodular, PST 0,Portal invasion, N1, M1,Sorafenib,Portal pressure/bilirubin,3 nodules 3 cm,Intermediate stage,PST 2, Child-Pugh C,Very early stage,Single 2 cm,Early stage,Single or 3 nodules 3 cm, PST 0,Adv
12、anced stage,Portal invasion,N1, M1, PST 1-2,PST 0, Child-Pugh A,Resection,Symptomatic (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 mos,Approved other options such as drug-eluting beads, radiolabell
13、ed yttrium glass beads, radiolabelled lipiodol, or immunotherapy cannot be recommended as standard therapy for advanced HCC outside clinical trials,Bruix J, et al. Hepatology. 2005;42:1208-1236.,TACE,Intra-arterial Locoregional Therapy,Established TACE Radioembolization: yttrium-90 radioactive micro
14、spheres Undergoing clinical trials Drug-eluting beads,Primary Treatment Modality Used in Korea,TACE 48.2%,RFA 1.5%,Surgery 11.2%,Chemotherapy 7.5%,Radiotherapy 2.1%,Conservative treatment 29.5%,N = 1078,Joong-Won Park, MD, National Cancer Center. Adapted with permission.,Chemoembolization: Randomize
15、d Trials (Nearly Identical Techniques),Llovet 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
16、 JM, et al. Lancet. 2002;359:1734-1739.,Chemoembolization: Predictors of Survival,Lo et al1 Absence of presenting symptoms (ECOG PS 5 cm) Okuda stage (I vs II) Llovet et al2 Absence 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 pati
