Skip to main content
Latest news
Browse specialties
Breast cancer Genitourinary cancers Lung & thoracic cancers
In focus
Next-generation sequencing: Emerging biomarkers in thyroid and NSCLCs ctDNA and bladder cancer: Current understanding and beyond ROS1 fusion-positive NSCLC NSCLC driver mutations: Discussing the importance of RET, ALK and ROS1 alterations in NSCLC Early-stage NSCLC management: Surgery, targeted treatment and immunotherapy ALK fusion-positive NSCLC: International approaches to management RET fusion-positive NSCLC: Informing on the use of pralsetinib for patients with RET fusion-positive, advanced NSCLC COVID-19 & cancer
Conferences
SABCS 2022 ESMO 2022 2022 ASCO Annual Meeting
About us
Medicine Matters Oncology
EXTENDED SEARCH
Top

14-02-2017 | Hepatocellular carcinoma | Article

9. Primary Liver Cancer: Background and Clinical Evidence

Authors: Florence K. Keane, MD, Theodore Hong, MD

Publisher: Springer International Publishing

Login to get access

Abstract

The incidence of primary liver cancers continues to increase worldwide. In this chapter, we discuss the risk factors, screening options, and staging classification systems for both hepatocellular carcinoma and intrahepatic cholangiocarcinoma. We also review management options for early-stage, locally advanced, and metastatic disease.
Literature
1.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7–30.CrossRefPubMed
2.
American Cancer Society. Global cancer facts & figures. 3 ed. Atlanta: The society; 2015.
3.
El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011;365(12):1118–27.CrossRefPubMed
4.
Shaib YH, Davila JA, McGlynn K, El-Serag HB. Rising incidence of intrahepatic cholangiocarcinoma in the United States: a true increase? J Hepatol. 2004;40(3):472–7.CrossRefPubMed
5.
Patel T. Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the United States. Hepatology. 2001;33(6):1353–7.CrossRefPubMed
6.
Lee YM, Kaplan MM. Primary sclerosing cholangitis. N Engl J Med. 1995;332(14):924–33.CrossRefPubMed
7.
Khaderi SA, Sussman NL. Screening for malignancy in primary sclerosing cholangitis (PSC). Curr Gastroenterol Rep. 2015;17(4):17.CrossRefPubMed
8.
Singal A, Volk ML, Waljee A, et al. Meta-analysis: surveillance with ultrasound for early-stage hepatocellular carcinoma in patients with cirrhosis. Aliment Pharmacol Ther. 2009;30(1):37–47.CrossRefPubMed
9.
Razumilava N, Gores GJ, Lindor KD. Cancer surveillance in patients with primary sclerosing cholangitis. Hepatology. Nov 2011;54(5):1842–52.CrossRefPubMedPubMedCentral
10.
Schlageter M, Terracciano LM, D'Angelo S, Sorrentino P. Histopathology of hepatocellular carcinoma. World J Gastroenterol. 2014;20(43):15955–64.CrossRefPubMedPubMedCentral
11.
Liver Cancer Study Group of Japan General rules for the clinical and pathological study of primary liver cancer. 2nd English Edition ed. Tokyo: Kanehara; 2003.
12.
Edge S, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A. AJCC cancer staging handbook. 7 ed. Chicago: Springer; 2011.
13.
Vauthey JN, Ribero D, Abdalla EK, et al. Outcomes of liver transplantation in 490 patients with hepatocellular carcinoma: validation of a uniform staging after surgical treatment. J Am Coll Surg. 2007;204(5):1016–27. discussion 1027-1018CrossRefPubMed
14.
Llovet JM, Bru C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis. 1999;19(3):329–38.CrossRefPubMed
15.
Okuda K, Ohtsuki T, Obata H, et al. Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Study of 850 patients. Cancer. 1985;56(4):918–28.CrossRefPubMed
16.
A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients: the Cancer of the Liver Italian Program (CLIP) investigators. Hepatol. 1998;28(3):751–5.
17.
Prospective validation of the CLIP score: a new prognostic system for patients with cirrhosis and hepatocellular carcinoma: the Cancer of the Liver Italian Program (CLIP) Investigators. Hepatol. 2000;31(4):840–5.
18.
Cho YK, Chung JW, Kim JK, et al. Comparison of 7 staging systems for patients with hepatocellular carcinoma undergoing transarterial chemoembolization. Cancer. 2008;112(2):352–61.CrossRefPubMed
19.
Nathan H, Aloia TA, Vauthey JN, et al. A proposed staging system for intrahepatic cholangiocarcinoma. Ann Surg Oncol. 2009;16(1):14–22.CrossRefPubMed
20.
Child CG, Turcotte JG. Surgery and portal hypertension. Major Probl Clin Surg. 1964;1:1–85.PubMed
21.
Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 1973;60(8):646–9.CrossRefPubMed
22.
Malinchoc M, Kamath PS, Gordon FD, Peine CJ, Rank J, ter Borg PC. A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts. Hepatology. 2000;31(4):864–71.CrossRefPubMed
23.
Salerno F, Merli M, Cazzaniga M, et al. MELD score is better than Child-Pugh score in predicting 3-month survival of patients undergoing transjugular intrahepatic portosystemic shunt. J Hepatol. 2002;36(4):494–500.CrossRefPubMed
24.
Wiesner R, Edwards E, Freeman R, et al. Model for end-stage liver disease (MELD) and allocation of donor livers. Gastroenterology. 2003;124(1):91–6.CrossRefPubMed
25.
Johnson PJ, Berhane S, Kagebayashi C, et al. Assessment of liver function in patients with hepatocellular carcinoma: a new evidence-based approach-the ALBI grade. J Clin Oncol. 2015;33(6):550–8.CrossRefPubMed
26.
El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132(7):2557–76.CrossRefPubMed
27.
Schulze K, Imbeaud S, Letouze E, Alexandrov LB. Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets. Nat Genet. 2015;47(5):505–11.CrossRefPubMedPubMedCentral
28.
Borger DR, Tanabe KK, Fan KC, et al. Frequent mutation of isocitrate dehydrogenase (IDH)1 and IDH2 in cholangiocarcinoma identified through broad-based tumor genotyping. Oncologist. 2012;17(1):72–9.CrossRefPubMed
29.
Zhu AX, Borger DR, Kim Y, et al. Genomic profiling of intrahepatic cholangiocarcinoma: refining prognosis and identifying therapeutic targets. Ann Surg Oncol. 2014;21(12):3827–34.CrossRefPubMedPubMedCentral
30.
Lau WY, Leung TW, Yu SC, Ho SK. Percutaneous local ablative therapy for hepatocellular carcinoma: a review and look into the future. Ann Surg. 2003;237(2):171–9.PubMedPubMedCentral
31.
Liver Cancer Study Group of J. Primary liver cancer in Japan. Clinicopathologic features and results of surgical treatment. Ann Surg. 1990;211(3):277–87.
32.
Bruix J, Takayama T, Mazzaferro V, et al. Adjuvant sorafenib for hepatocellular carcinoma after resection or ablation (STORM): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2015;16(13):1344–54.CrossRefPubMed
33.
Yin J, Li N, Han Y, et al. Effect of antiviral treatment with nucleotide/nucleoside analogs on postoperative prognosis of hepatitis B virus-related hepatocellular carcinoma: a two-stage longitudinal clinical study. J Clin Oncol. 2013;31(29):3647–55.CrossRefPubMed
34.
Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334(11):693–9.CrossRefPubMed
35.
Duffy JP, Vardanian A, Benjamin E, et al. Liver transplantation criteria for hepatocellular carcinoma should be expanded: a 22-year experience with 467 patients at UCLA. Ann Surg. 2007;246(3):502–9. discussion 509-511CrossRefPubMedPubMedCentral
36.
Mazzaferro V, Llovet JM, Miceli R, et al. 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.CrossRefPubMed
37.
Merchant N, David CS, Cunningham SC. Early hepatocellular carcinoma: transplantation versus Resection: the case for liver resection. Int J Hepatol. 2011;2011:142085.CrossRefPubMedPubMedCentral
38.
Llovet JM, Fuster J, Bruix J. Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation. Hepatology. 1999;30(6):1434–40.CrossRefPubMed
39.
Belghiti J, Cortes A, Abdalla EK, et al. Resection prior to liver transplantation for hepatocellular carcinoma. Ann Surg. 2003;238(6):885–92. discussion 892-883CrossRefPubMedPubMedCentral
40.
Adam R, Azoulay D, Castaing D, et al. Liver resection as a bridge to transplantation for hepatocellular carcinoma on cirrhosis: a reasonable strategy? Ann Surg. 2003;238(4):508–18. discussion 518-509PubMedPubMedCentral
41.
Huang J, Yan L, Cheng Z, et al. A randomized trial comparing radiofrequency ablation and surgical resection for HCC conforming to the Milan criteria. Ann Surg. 2010;252(6):903–12.CrossRefPubMed
42.
Chen MS, Li JQ, Zheng Y, et al. A prospective randomized trial comparing percutaneous local ablative therapy and partial hepatectomy for small hepatocellular carcinoma. Ann Surg. 2006;243(3):321–8.CrossRefPubMedPubMedCentral
43.
Feng K, Yan J, Li X, et al. A randomized controlled trial of radiofrequency ablation and surgical resection in the treatment of small hepatocellular carcinoma. J Hepatol. 2012;57(4):794–802.CrossRefPubMed
44.
Xu G, Qi FZ, Zhang JH, Cheng GF, Cai Y, Miao Y. Meta-analysis of surgical resection and radiofrequency ablation for early hepatocellular carcinoma. World J Surg Oncol. 2012;10:163.CrossRefPubMedPubMedCentral
45.
Llovet JM, Real MI, Montana X, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet. 2002;359(9319):1734–9.CrossRefPubMed
46.
Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology. 2003;37(2):429–42.CrossRefPubMed
47.
Camma 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.CrossRefPubMed
48.
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.CrossRefPubMed
49.
Lencioni R, Llovet JM, Han G, et al. Sorafenib or placebo plus TACE with doxorubicin-eluting beads for intermediate stage HCC: the SPACE trial. J Hepatol. 2016;64:1090.CrossRefPubMed
50.
Seong J, Lee IJ, Shim SJ, et al. A multicenter retrospective cohort study of practice patterns and clinical outcome on radiotherapy for hepatocellular carcinoma in Korea. Liver Int Off J Int Assoc Stud Liver. 2009;29(2):147–52.CrossRef
51.
Ben-Josef E, Normolle D, Ensminger WD, et al. Phase II trial of high-dose conformal radiation therapy with concurrent hepatic artery floxuridine for unresectable intrahepatic malignancies. J Clin Oncol. 2005;23(34):8739–47.CrossRefPubMed
52.
Keane FK, Tanguturi SK, Zhu AX, Dawson LA, Hong T. Radiotherapy for liver tumors. Hepatic Oncol. 2014;2(2):133–46.CrossRef
53.
Bujold A, Massey CA, Kim JJ, et al. Sequential phase I and II trials of stereotactic body radiotherapy for locally advanced hepatocellular carcinoma. J Clin Oncol. 2013;31(13):1631–9.CrossRefPubMed
54.
Hong TS, Wo JY, Beow YY, et al. A multi-institutional phase II study of high dose hypofractionated proton beam therapy in patients with localized, unresectable hepatocellular carcinoma and intrahepatic cholangiocarcinoma. J Clin Oncol. 2015;34:460. (In press)CrossRefPubMedPubMedCentral
55.
Nakayama H, Sugahara S, Tokita M, et al. Proton beam therapy for hepatocellular carcinoma: the University of Tsukuba experience. Cancer. 2009;115(23):5499–506.CrossRefPubMed
56.
Sanuki N, Takeda A, Oku Y, et al. Stereotactic body radiotherapy for small hepatocellular carcinoma: a retrospective outcome analysis in 185 patients. Acta Oncol. 2014;53(3):399–404.CrossRefPubMed
57.
Honda Y, Kimura T, Aikata H, et al. Stereotactic body radiation therapy combined with transcatheter arterial chemoembolization for small hepatocellular carcinoma. J Gastroenterol Hepatol. 2013;28(3):530–6.CrossRefPubMed
58.
Choi C, Koom WS, Kim TH, et al. A prospective phase 2 multicenter study for the efficacy of radiation therapy following incomplete transarterial chemoembolization in unresectable hepatocellular carcinoma. Int J Radiat Oncol Biol Phys. 2014;90(5):1051–60.CrossRefPubMed
59.
Zhong NB, Lv GM, Chen ZH. Stereotactic body radiotherapy combined with transarterial chemoembolization for huge (>/=10 cm) hepatocellular carcinomas: a clinical study. Mol Clin Oncol. 2014;2(5):839–44.PubMedPubMedCentral
60.
Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359(4):378–90.CrossRefPubMed
61.
Bruix J, Raoul JL, Sherman M, et al. Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: subanalyses of a phase III trial. J Hepatol. 2012;57(4):821–9.CrossRefPubMed
62.
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.CrossRefPubMed
63.
Maithel SK, Gamblin TC, Kamel I, Corona-Villalobos CP, Thomas M, Pawlik TM. Multidisciplinary approaches to intrahepatic cholangiocarcinoma. Cancer. 2013;119(22):3929–42.CrossRefPubMed
64.
Spolverato G, Vitale A, Cucchetti A, et al. Can hepatic resection provide a long-term cure for patients with intrahepatic cholangiocarcinoma? Cancer. 2015;121(22):3998–4006.CrossRefPubMed
65.
Mavros MN, Economopoulos KP, Alexiou VG, Pawlik TM. Treatment and prognosis for patients with Intrahepatic cholangiocarcinoma: systematic review and meta-analysis. JAMA Surg. 2014;149(6):565–74.CrossRefPubMed
66.
Ribero D, Pinna AD, Guglielmi A, et al. Surgical approach for long-term survival of patients with intrahepatic cholangiocarcinoma: a multi-institutional analysis of 434 patients. Arch Surg. 2012;147(12):1107–13.CrossRefPubMed
67.
Farges O, Fuks D, Boleslawski E, et al. Influence of surgical margins on outcome in patients with intrahepatic cholangiocarcinoma: a multicenter study by the AFC-IHCC-2009 study group. Ann Surg. 2011;254(5):824–9. discussion 830CrossRefPubMed
68.
DeOliveira ML, Cunningham SC, Cameron JL, et al. Cholangiocarcinoma: thirty-one-year experience with 564 patients at a single institution. Ann Surg. 2007;245(5):755–62.CrossRefPubMedPubMedCentral
69.
Horgan AM, Amir E, Walter T, Knox JJ. Adjuvant therapy in the treatment of biliary tract cancer: a systematic review and meta-analysis. J Clin Oncol. 2012;30(16):1934–40.CrossRefPubMed
70.
Jiang W, Zeng ZC, Tang ZY, et al. Benefit of radiotherapy for 90 patients with resected intrahepatic cholangiocarcinoma and concurrent lymph node metastases. J Cancer Res Clin Oncol. 2010;136(9):1323–31.CrossRefPubMed
71.
Benson 3rd AB, D'Angelica MI, Abrams TA, et al. Hepatobiliary cancers, version 2.2014. J Natl Compr Canc Netw. 2014;12(8):1152–82.PubMed
72.
Endo I, Gonen M, Yopp AC, et al. Intrahepatic cholangiocarcinoma: rising frequency, improved survival, and determinants of outcome after resection. Ann Surg. 2008;248(1):84–96.CrossRefPubMed
73.
Valle J, Wasan H, Palmer DH, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362(14):1273–81.CrossRefPubMed
74.
Valle JW, Furuse J, Jitlal M, et al. Cisplatin and gemcitabine for advanced biliary tract cancer: a meta-analysis of two randomised trials. Ann Oncol Off J Eur Soc Med Oncol ESMO. 2014;25(2):391–8.CrossRef
75.
Tse RV, Hawkins M, Lockwood G, et al. Phase I study of individualized stereotactic body radiotherapy for hepatocellular carcinoma and intrahepatic cholangiocarcinoma. J Clin Oncol. 2008;26(4):657–64.CrossRefPubMed
76.
Tao R, Krishnan S, Bhosale PR, et al. Ablative radiotherapy doses lead to a substantial prolongation of survival in patients with inoperable intrahepatic cholangiocarcinoma: a retrospective dose response analysis. J Clin Oncol. 2016;34(3):219–26.CrossRefPubMed
77.
Tanguturi SK, Wo JY, Zhu AX, Dawson LA, Hong TS. Radiation therapy for liver tumors: ready for inclusion in guidelines? Oncologist. 2014;19(8):868–79.CrossRefPubMedPubMedCentral
78.
Chen YX, Zeng ZC, Tang ZY, et al. Determining the role of external beam radiotherapy in unresectable intrahepatic cholangiocarcinoma: a retrospective analysis of 84 patients. BMC Cancer. 2010;10:492.CrossRefPubMedPubMedCentral
79.
Clinicaltrials.​gov identifier NCT01730937. Accessed 30 Sept 2015.
80.
Clinicaltrials.​gov identifier NCT01135056. Accessed 1 Apr 2015.
81.
Clinicaltrials.​gov identifier NCT02200042. Accessed 31 Mar 2016.