Download PDF
Semin Liver Dis 2012; 32(04): 348-359
DOI: 10.1055/s-0032-1329906
Editors' Choice
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Heterogeneity of Patients with Intermediate (BCLC B) Hepatocellular Carcinoma: Proposal for a Subclassification to Facilitate Treatment Decisions

Luigi Bolondi
1   Division of Internal Medicine, Department of Digestive Disease and Internal Medicine, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy
,
Andrew Burroughs
2   The Royal Free Sheila Sherlock Liver Centre, The Royal Free Hospital and UCL Institute for Liver and Digestive Health, UCL London, London, UK
,
Jean-François Dufour
3   University Clinic for Visceral Surgery and Medicine, Inselspital, Bern and Hepatology, Department of Clinical Research, University of Bern, Bern, Switzerland
,
Peter R. Galle
4   University Medical Center, I. Medical Department, Johannes Gutenberg University, Mainz, Germany
,
Vincenzo Mazzaferro
5   Istituto Nazionale Tumori (National Cancer Institute) IRCCS Foundation, Milan, Italy
,
Fabio Piscaglia
1   Division of Internal Medicine, Department of Digestive Disease and Internal Medicine, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy
,
Jean Luc Raoul
6   Department of Medical Oncology, Institut Paoli-Calmettes, Marseille, France
,
Bruno Sangro
7   Liver Unit, Clinica Universidad de Navarra, and Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBERehd), Pamplona, Spain
› Author Affiliations
Further Information

Publication History

Publication Date:
08 February 2013 (online)

    Permissions and Reprints

Abstract

The intermediate stage of hepatocellular carcinoma (HCC) comprises a highly heterogeneous patient population and therefore poses unique challenges for therapeutic management, different from the early and advanced stages. Patients classified as having intermediate HCC by the Barcelona Clinic Liver Cancer (BCLC) staging system present with varying tumor burden and liver function. Transarterial chemoembolization (TACE) is currently recommended as the standard of care in this setting, but there is considerable variation in the clinical benefit patients derive from this treatment.

In April 2012, a panel of experts convened to discuss unresolved issues surrounding the application of current guidelines when managing patients with intermediate HCC. The meeting explored the applicability of a subclassification system for intermediate HCC patients to tailor therapeutic interventions based on the evidence available to date and expert opinion. The present report summarizes the proposal of the expert panel: four substages of intermediate HCC patients, B1 to B4.

Keywords

hepatocellular carcinoma - sorafenib - transarterial chemoembolization - radioembolization - Barcelona Clinic Liver Cancer
 

  • References

  • 1 National Cancer Institute. SEER Stat Fact Sheets: Liver and Intrahepatic Bile Duct. Available at: http://seer.cancer.gov/statfacts/html/livibd.html . Accessed August 24, 2012.
    PubMed
  • 2 Berrino F, De Angelis R, Sant M , et al; EUROCARE Working group. Survival for eight major cancers and all cancers combined for European adults diagnosed in 1995-99: results of the EUROCARE-4 study. Lancet Oncol 2007; 8 (9) 773-783
    CrossrefPubMedSearch in Google Scholar
  • 3 Verdecchia A, Francisci S, Brenner H , et al; EUROCARE-4 Working Group. Recent cancer survival in Europe: a 2000-02 period analysis of EUROCARE-4 data. Lancet Oncol 2007; 8 (9) 784-796
    CrossrefPubMedSearch in Google Scholar
  • 4 Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet 2012; 379 (9822) 1245-1255
    CrossrefPubMedSearch in Google Scholar
  • 5 Marrero JA, Fontana RJ, Barrat A , et al. Prognosis of hepatocellular carcinoma: comparison of 7 staging systems in an American cohort. Hepatology 2005; 41 (4) 707-716
    CrossrefPubMedSearch in Google Scholar
  • 6 Cillo U, Vitale A, Grigoletto F , et al. Prospective validation of the Barcelona Clinic Liver Cancer staging system. J Hepatol 2006; 44 (4) 723-731
    CrossrefPubMedSearch in Google Scholar
  • 7 Guglielmi A, Ruzzenente A, Pachera S , et al. Comparison of seven staging systems in cirrhotic patients with hepatocellular carcinoma in a cohort of patients who underwent radiofrequency ablation with complete response. Am J Gastroenterol 2008; 103 (3) 597-604
    CrossrefPubMedSearch in Google Scholar
  • 8 Bruix J, Sherman M. American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: an update. Hepatology 2011; 53 (3) 1020-1022
    CrossrefPubMedSearch in Google Scholar
  • 9 European Association For The Study Of The Liver; European Organisation For Research And Treatment Of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 2012; 56 (4) 908-943
    PubMedSearch in Google Scholar
  • 10 Schwartz M, Roayaie S, Konstadoulakis M. Strategies for the management of hepatocellular carcinoma. Nat Clin Pract Oncol 2007; 4 (7) 424-432
    CrossrefPubMedSearch in Google Scholar
  • 11 Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet 2003; 362 (9399) 1907-1917
    CrossrefPubMedSearch in Google Scholar
  • 12 Clark HP, Carson WF, Kavanagh PV, Ho CP, Shen P, Zagoria RJ. Staging and current treatment of hepatocellular carcinoma. Radiographics 2005; 25 (Suppl. 01) S3-S23
    CrossrefPubMedSearch in Google Scholar
  • 13 Llovet JM. Treatment of Hepatocellular Carcinoma. Curr Treat Options Gastroenterol 2004; 7 (6) 431-441
    CrossrefPubMedSearch in Google Scholar
  • 14 Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival. Hepatology 2003; 37 (2) 429-442
    CrossrefPubMedSearch in Google Scholar
  • 15 Piscaglia F, Bolondi L. The intermediate hepatocellular carcinoma stage: Should treatment be expanded?. Dig Liver Dis 2010; 42 (Suppl. 03) S258-S263
    CrossrefPubMedSearch in Google Scholar
  • 16 D'Avola D, Iñarrairaegui M, Pardo F , et al. Prognosis of hepatocellular carcinoma in relation to treatment across BCLC stages. Ann Surg Oncol 2011; 18 (7) 1964-1971
    CrossrefPubMedSearch in Google Scholar
  • 17 Marelli L, Stigliano R, Triantos C , et al. Transarterial therapy for hepatocellular carcinoma: which technique is more effective? A systematic review of cohort and randomized studies. Cardiovasc Intervent Radiol 2007; 30 (1) 6-25
    CrossrefPubMedSearch in Google Scholar
  • 18 Tsochatzis EA, Germani G, Burroughs AK. Transarterial chemoembolization, transarterial chemotherapy, and intra-arterial chemotherapy for hepatocellular carcinoma treatment. Semin Oncol 2010; 37 (2) 89-93
    CrossrefPubMedSearch in Google Scholar
  • 19 Terzi E, Golfieri R, Piscaglia F , et al. Response rate and clinical outcome of HCC after first and repeated cTACE performed “on demand”. J Hepatol 2012; ; Epub ahead of print
    PubMedSearch in Google Scholar
  • 20 Takayasu K, Arii S, Kudo M , et al. Superselective transarterial chemoembolization for hepatocellular carcinoma. Validation of treatment algorithm proposed by Japanese guidelines. J Hepatol 2012; 56 (4) 886-892
    CrossrefPubMedSearch in Google Scholar
  • 21 Oliveri RS, Wetterslev J, Gluud C. Transarterial (chemo)embolisation for unresectable hepatocellular carcinoma. Cochrane Database Syst Rev 2011; (3) CD004787
    PubMedSearch in Google Scholar
  • 22 Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis 2010; 30 (1) 52-60
    Thieme ConnectPubMedSearch in Google Scholar
  • 23 Gillmore R, Stuart S, Kirkwood A , et al. EASL and mRECIST responses are independent prognostic factors for survival in hepatocellular cancer patients treated with transarterial embolization. J Hepatol 2011; 55 (6) 1309-1316
    CrossrefPubMedSearch in Google Scholar
  • 24 Cammà C, Schepis F, Orlando A , et al. Transarterial chemoembolization for unresectable hepatocellular carcinoma: meta-analysis of randomized controlled trials. Radiology 2002; 224 (1) 47-54
    CrossrefPubMedSearch in Google Scholar
  • 25 Raoul JL, Sangro B, Forner A , et al. Evolving strategies for the management of intermediate-stage hepatocellular carcinoma: available evidence and expert opinion on the use of transarterial chemoembolization. Cancer Treat Rev 2011; 37 (3) 212-220
    CrossrefPubMedSearch in Google Scholar
  • 26 Lencioni R. Loco-regional treatment of hepatocellular carcinoma. Hepatology 2010; 52 (2) 762-773
    CrossrefPubMedSearch in Google Scholar
  • 27 Meyer T, Roughton M, Yu D , et al. A randomized phase II/III trial of three weekly cisplatin based transarterial chemoembolization (TACE) versus embolization (TAE) alone for hepatocellular cancer (HCC) [Abstract 4025]. J Clin Oncol 2010; 28 (suppl): 15s
    PubMedSearch in Google Scholar
  • 28 Llovet JM, Real MI, Montaña X , et al; Barcelona Liver Cancer Group. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet 2002; 359 (9319) 1734-1739
    CrossrefPubMedSearch in Google Scholar
  • 29 Golfieri R, Cappelli A, Cucchetti A , et al. Efficacy of selective transarterial chemoembolization in inducing tumor necrosis in small (<5 cm) hepatocellular carcinomas. Hepatology 2011; 53 (5) 1580-1589
    CrossrefPubMedSearch in Google Scholar
  • 30 Varela M, Real MI, Burrel M , et al. Chemoembolization of hepatocellular carcinoma with drug eluting beads: efficacy and doxorubicin pharmacokinetics. J Hepatol 2007; 46 (3) 474-481
    CrossrefPubMedSearch in Google Scholar
  • 31 Lammer J, Malagari K, Vogl T , et al; PRECISION V Investigators. Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study. Cardiovasc Intervent Radiol 2010; 33 (1) 41-52
    CrossrefPubMedSearch in Google Scholar
  • 32 Malagari K, Pomoni M, Kelekis A , et al. Prospective randomized comparison of chemoembolization with doxorubicin-eluting beads and bland embolization with BeadBlock for hepatocellular carcinoma. Cardiovasc Intervent Radiol 2010; 33 (3) 541-551
    CrossrefPubMedSearch in Google Scholar
  • 33 Grieco A, Marcoccia S, Miele L , et al. Transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma in cirrhotics: functional hepatic reserve and survival. Hepatogastroenterology 2003; 50 (49) 207-212
    PubMedSearch in Google Scholar
  • 34 Saccheri S, Lovaria A, Sangiovanni A , et al. Segmental transcatheter arterial chemoembolization treatment in patients with cirrhosis and inoperable hepatocellular carcinomas. J Vasc Interv Radiol 2002; 13 (10) 995-999
    CrossrefPubMedSearch in Google Scholar
  • 35 Lu W, Li Y, He X, Chen Y. Transcatheter arterial chemoembolization for hepatocellular carcinoma in patients with cirrhosis: evaluation of two kinds of dosages of anticancer drugs and analysis of prognostic factors. Hepatogastroenterology 2003; 50 (54) 2079-2083
    PubMedSearch in Google Scholar
  • 36 Ikeda K, Kumada H, Saitoh S, Arase Y, Chayama K. Effect of repeated transcatheter arterial embolization on the survival time in patients with hepatocellular carcinoma. An analysis by the Cox proportional hazard model. Cancer 1991; 68 (10) 2150-2154
    CrossrefPubMedSearch in Google Scholar
  • 37 Herber SC, Otto G, Schneider J , et al. Transarterial chemoembolization in patients not eligible for liver transplantation: single-center results. AJR Am J Roentgenol 2008; 190 (4) 1035-1042
    CrossrefPubMedSearch in Google Scholar
  • 38 Ernst O, Sergent G, Mizrahi D, Delemazure O, Paris JC, L'Herminé C. Treatment of hepatocellular carcinoma by transcatheter arterial chemoembolization: comparison of planned periodic chemoembolization and chemoembolization based on tumor response. AJR Am J Roentgenol 1999; 172 (1) 59-64
    CrossrefPubMedSearch in Google Scholar
  • 39 Forner A, Ayuso C, Varela M , et al. Evaluation of tumor response after locoregional therapies in hepatocellular carcinoma: are response evaluation criteria in solid tumors reliable?. Cancer 2009; 115 (3) 616-623
    CrossrefPubMedSearch in Google Scholar
  • 40 Llovet JM, Ricci S, Mazzaferro V , et al; SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008; 359 (4) 378-390
    CrossrefPubMedSearch in Google Scholar
  • 41 Kulik LM, Carr BI, Mulcahy MF , et al. Safety and efficacy of 90Y radiotherapy for hepatocellular carcinoma with and without portal vein thrombosis. Hepatology 2008; 47 (1) 71-81
    CrossrefPubMedSearch in Google Scholar
  • 42 Hsu CY, Hsia CY, Huang YH , et al. Comparison of surgical resection and transarterial chemoembolization for hepatocellular carcinoma beyond the Milan criteria: a propensity score analysis. Ann Surg Oncol 2012; 19 (3) 842-849
    CrossrefPubMedSearch in Google Scholar
  • 43 Zhang ZM, Guo JX, Zhang ZC, Jiang N, Zhang ZY, Pan LJ. Therapeutic options for intermediate-advanced hepatocellular carcinoma. World J Gastroenterol 2011; 17 (13) 1685-1689
    CrossrefPubMedSearch in Google Scholar
  • 44 Silva MF, Sherman M. Criteria for liver transplantation for HCC: what should the limits be?. J Hepatol 2011; 55 (5) 1137-1147
    CrossrefPubMedSearch in Google Scholar
  • 45 Mazzaferro V, Llovet JM, Miceli R , et al; Metroticket Investigator Study Group. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol 2009; 10 (1) 35-43
    CrossrefPubMedSearch in Google Scholar
  • 46 Clavien PA, Lesurtel M, Bossuyt PM, Gores GJ, Langer B, Perrier A. OLT for HCC Consensus Group. Recommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report. Lancet Oncol 2012; 13 (1) e11-e22
    CrossrefPubMedSearch in Google Scholar
  • 47 Jelic S, Sotiropoulos GC. ESMO Guidelines Working Group. Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010; 21 (Suppl. 05) v59-v64
    CrossrefPubMedSearch in Google Scholar
  • 48 Ravaioli M, Grazi GL, Piscaglia F , et al. Liver transplantation for hepatocellular carcinoma: results of down-staging in patients initially outside the Milan selection criteria. Am J Transplant 2008; 8 (12) 2547-2557
    CrossrefPubMedSearch in Google Scholar
  • 49 Vibert E, Azoulay D, Hoti E , et al. Progression of alphafetoprotein before liver transplantation for hepatocellular carcinoma in cirrhotic patients: a critical factor. Am J Transplant 2010; 10 (1) 129-137
    CrossrefPubMedSearch in Google Scholar
  • 50 Yao FY, Kerlan Jr RK, Hirose R , et al. Excellent outcome following down-staging of hepatocellular carcinoma prior to liver transplantation: an intention-to-treat analysis. Hepatology 2008; 48 (3) 819-827
    CrossrefPubMedSearch in Google Scholar
  • 51 Llovet JM, Ricci S, Mazzaferro V , et al. Sorafenib improves survival in advanced hepatocellular carcinoma (HCC): results of a Phase III randomized placebo-controlled trial (SHARP trial). Paper presented at: American Society of Clinical Oncology Annual Meeting; June 1–5, 2007; Chicago, IL
    PubMed
  • 52 Cheng AL, Kang YK, Chen Z , et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 2009; 10 (1) 25-34
    CrossrefPubMedSearch in Google Scholar
  • 53 Bruix J, Raoul JL, Sherman M , et al. Efficacy and safety of sorafenib in patients with hepatocellular carcinoma (HCC): Subanalysis of SHARP trial based on Barcelona Clinic Liver Cancer (BCLC) stage. J Hepatol 2009; 50 (Suppl. 01) S28-S29
    PubMedSearch in Google Scholar
  • 54 Lencioni R, Venook AP, Marrero JA , et al. Second Interim Results of the GIDEON (Global Investigation of Therapeutic DEcisions in HCC and of Its Treatment With SorafeNib) Study - Barcelona-Clinic Liver Cancer (BCLC) Stage Subgroup Analysis. Abs 6500. Abstract presented at: The European Multidisciplinary Cancer Congress; September 23–27, 2011; Stockholm, Sweden
    PubMed
  • 55 Marrero JA, Lencioni R, Kudo M , et al. Global Investigation of Therapeutic Decisions in Hepatocellular Carcinoma and of its Treatment with Sorafenib (GIDEON) second interim analysis in more than 1,500 patients: Clinical findings in patients with liver dysfunction. J Clin Oncol 2011; 29: 4001
    PubMedSearch in Google Scholar
  • 56 Iavarone M, Cabibbo G, Piscaglia F , et al; SOFIA (SOraFenib Italian Assessment) study group. Field-practice study of sorafenib therapy for hepatocellular carcinoma: a prospective multicenter study in Italy. Hepatology 2011; 54 (6) 2055-2063
    CrossrefPubMedSearch in Google Scholar
  • 57 Piscaglia F, Trimarchi C, Terzi E , et al. The rate of HCC patients in Child-Pugh B untreatable with effective strategies according to AASLD guidelines increases with the progression of specific Child-Pugh score. Hepatology 2010; 52: 1168A
    PubMedSearch in Google Scholar
  • 58 Burrel M, Reig M, Forner A , et al. Survival of patients with hepatocellular carcinoma treated by transarterial chemoembolisation (TACE) using drug eluting beads. Implications for clinical practice and trial design. J Hepatol 2012; 56 (6) 1330-1335
    CrossrefPubMedSearch in Google Scholar
  • 59 Salem R, Lewandowski RJ, Mulcahy MF , et al. Radioembolization for hepatocellular carcinoma using Yttrium-90 microspheres: a comprehensive report of long-term outcomes. Gastroenterology 2010; 138 (1) 52-64
    CrossrefPubMedSearch in Google Scholar
  • 60 Hilgard P, Hamami M, Fouly AE , et al. Radioembolization with yttrium-90 glass microspheres in hepatocellular carcinoma: European experience on safety and long-term survival. Hepatology 2010; 52 (5) 1741-1749
    CrossrefPubMedSearch in Google Scholar
  • 61 Sangro B, Carpanese L, Cianni R , et al; European Network on Radioembolization with Yttrium-90 Resin Microspheres (ENRY). Survival after yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona clinic liver cancer stages: a European evaluation. Hepatology 2011; 54 (3) 868-878
    CrossrefPubMedSearch in Google Scholar
  • 62 Sangro B, Iñarrairaegui M, Bilbao JI. Radioembolization for hepatocellular carcinoma. J Hepatol 2012; 56 (2) 464-473
    CrossrefPubMedSearch in Google Scholar
  • 63 Andreana L, Isgrò G, Marelli L , et al. Treatment of hepatocellular carcinoma (HCC) by intra-arterial infusion of radio-emitter compounds: trans-arterial radio-embolisation of HCC. Cancer Treat Rev 2012; 38 (6) 641-649
    CrossrefPubMedSearch in Google Scholar
  • 64 Iñarrairaegui M, Pardo F, Bilbao JI , et al. Response to radioembolization with yttrium-90 resin microspheres may allow surgical treatment with curative intent and prolonged survival in previously unresectable hepatocellular carcinoma. Eur J Surg Oncol 2012; 38 (7) 594-601
    CrossrefPubMedSearch in Google Scholar
  • 65 Lewandowski RJ, Kulik LM, Riaz A , et al. A comparative analysis of transarterial downstaging for hepatocellular carcinoma: chemoembolization versus radioembolization. Am J Transplant 2009; 9 (8) 1920-1928
    CrossrefPubMedSearch in Google Scholar
  • 66 Lencioni R. Management of hepatocellular carcinoma with transarterial chemoembolization in the era of systemic targeted therapy. Crit Rev Oncol Hematol 2012; 83 (2) 216-224
    CrossrefPubMedSearch in Google Scholar
  • 67 Li X, Feng GS, Zheng CS, Zhuo CK, Liu X. Expression of plasma vascular endothelial growth factor in patients with hepatocellular carcinoma and effect of transcatheter arterial chemoembolization therapy on plasma vascular endothelial growth factor level. World J Gastroenterol 2004; 10 (19) 2878-2882
    PubMedSearch in Google Scholar
  • 68 Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature 2000; 407 (6801) 249-257
    CrossrefPubMedSearch in Google Scholar
  • 69 Dufour JF, Hoppe H, Heim MH , et al. Continuous administration of sorafenib in combination with transarterial chemoembolization in patients with hepatocellular carcinoma: results of a phase I study. Oncologist 2010; 15 (11) 1198-1204
    CrossrefPubMedSearch in Google Scholar
  • 70 Chung Y, Kim B, Chen C , et al. Study in Asia of the combination of transcatheter arterial chemoembolization (TACE) with sorafenib in patients with hepatocellular carcinoma (HCC) trial (START): Second interim safety and efficacy analysis. J Clin Oncol 2010; 28: 4026
    PubMedSearch in Google Scholar
  • 71 Lencioni R, Llovet JM, Han G , et al. Sorafenib or placebo in combination with transarterial chemoembolization (TACE) with doxorubicin-eluting beads (DEBDOX) for intermediate-stage hepatocellular carcinoma (HCC): Phase II, randomized, double-blind SPACE trial. . [Abstract LBA154] J Clin Oncol 2012; 30 (suppl)
    PubMedSearch in Google Scholar
  • 72 Akamatsu M, Yoshida H, Obi S , et al. Evaluation of transcatheter arterial embolization prior to percutaneous tumor ablation in patients with hepatocellular carcinoma: a randomized controlled trial. Liver Int 2004; 24 (6) 625-629
    CrossrefPubMedSearch in Google Scholar
  • 73 Bartolozzi C, Lencioni R, Caramella D , et al. Treatment of large HCC: transcatheter arterial chemoembolization combined with percutaneous ethanol injection versus repeated transcatheter arterial chemoembolization. Radiology 1995; 197 (3) 812-818
    PubMedSearch in Google Scholar
  • 74 Becker G, Soezgen T, Olschewski M, Laubenberger J, Blum HE, Allgaier HP. Combined TACE and PEI for palliative treatment of unresectable hepatocellular carcinoma. World J Gastroenterol 2005; 11 (39) 6104-6109
    PubMedSearch in Google Scholar
  • 75 Marelli L, Stigliano R, Triantos C , et al. Treatment outcomes for hepatocellular carcinoma using chemoembolization in combination with other therapies. Cancer Treat Rev 2006; 32 (8) 594-606
    CrossrefPubMedSearch in Google Scholar
  • 76 Cheung TT, Ng KK, Chok KS , et al. Combined resection and radiofrequency ablation for multifocal hepatocellular carcinoma: prognosis and outcomes. World J Gastroenterol 2010; 16 (24) 3056-3062
    CrossrefPubMedSearch in Google Scholar
  • 77 NCCN. NCCN Clinical Practice Guidelines in Oncology. Hepatobiliary Cancer. V2.2012. Available at: www.nccn.org . Accessed August 24, 2012
    PubMed
  • 78 Kudo M, Izumi N, Kokudo N , et al; HCC Expert Panel of Japan Society of Hepatology. Management of hepatocellular carcinoma in Japan: consensus-based clinical practice guidelines proposed by the Japan Society of Hepatology (JSH) 2010 updated version. Dig Dis 2011; 29 (3) 339-364
    CrossrefPubMedSearch in Google Scholar
  • 79 Omata M, Lesmana LA, Tateishi R , et al. Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma. Hepatol Int 2010; 4 (2) 439-474
    CrossrefPubMedSearch in Google Scholar
  • 80 Tournoux-Facon C, Paoletti X, Barbare JC , et al. Development and validation of a new prognostic score of death for patients with hepatocellular carcinoma in palliative setting. J Hepatol 2011; 54 (1) 108-114
    CrossrefPubMedSearch in Google Scholar
  • 81 Llovet JM, Bustamante J, Castells A , et al. Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for the design and evaluation of therapeutic trials. Hepatology 1999; 29 (1) 62-67
    CrossrefPubMedSearch in Google Scholar
  • 82 Bruix J, Sala M, Llovet JM. Chemoembolization for hepatocellular carcinoma. Gastroenterology 2004; 127 (5) (Suppl. 01) S179-S188
    CrossrefPubMedSearch in Google Scholar