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.
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References
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7–30.
American Cancer Society. Global cancer facts & figures. 3 ed. Atlanta: The society; 2015.
El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011;365(12):1118–27.
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.
Patel T. Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the United States. Hepatology. 2001;33(6):1353–7.
Lee YM, Kaplan MM. Primary sclerosing cholangitis. N Engl J Med. 1995;332(14):924–33.
Khaderi SA, Sussman NL. Screening for malignancy in primary sclerosing cholangitis (PSC). Curr Gastroenterol Rep. 2015;17(4):17.
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.
Razumilava N, Gores GJ, Lindor KD. Cancer surveillance in patients with primary sclerosing cholangitis. Hepatology. Nov 2011;54(5):1842–52.
Schlageter M, Terracciano LM, D'Angelo S, Sorrentino P. Histopathology of hepatocellular carcinoma. World J Gastroenterol. 2014;20(43):15955–64.
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.
Edge S, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A. AJCC cancer staging handbook. 7 ed. Chicago: Springer; 2011.
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 1027-1018
Llovet JM, Bru C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis. 1999;19(3):329–38.
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.
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.
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.
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.
Nathan H, Aloia TA, Vauthey JN, et al. A proposed staging system for intrahepatic cholangiocarcinoma. Ann Surg Oncol. 2009;16(1):14–22.
Child CG, Turcotte JG. Surgery and portal hypertension. Major Probl Clin Surg. 1964;1:1–85.
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.
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.
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.
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.
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.
El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132(7):2557–76.
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.
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.
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.
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.
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.
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.
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.
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.
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 509-511
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.
Merchant N, David CS, Cunningham SC. Early hepatocellular carcinoma: transplantation versus Resection: the case for liver resection. Int J Hepatol. 2011;2011:142085.
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.
Belghiti J, Cortes A, Abdalla EK, et al. Resection prior to liver transplantation for hepatocellular carcinoma. Ann Surg. 2003;238(6):885–92. discussion 892-883
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 518-509
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.
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.
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.
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.
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.
Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology. 2003;37(2):429–42.
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.
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.
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.
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.
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.
Keane FK, Tanguturi SK, Zhu AX, Dawson LA, Hong T. Radiotherapy for liver tumors. Hepatic Oncol. 2014;2(2):133–46.
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.
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)
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.
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.
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.
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.
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.
Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359(4):378–90.
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.
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.
Maithel SK, Gamblin TC, Kamel I, Corona-Villalobos CP, Thomas M, Pawlik TM. Multidisciplinary approaches to intrahepatic cholangiocarcinoma. Cancer. 2013;119(22):3929–42.
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.
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.
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.
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 830
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Clinicaltrials.gov identifier NCT01730937. Accessed 30 Sept 2015.
Clinicaltrials.gov identifier NCT01135056. Accessed 1 Apr 2015.
Clinicaltrials.gov identifier NCT02200042. Accessed 31 Mar 2016.
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Keane, F.K., Hong, T. (2017). Primary Liver Cancer: Background and Clinical Evidence. In: Hong, T., Das, P. (eds) Radiation Therapy for Gastrointestinal Cancers. Springer, Cham. https://doi.org/10.1007/978-3-319-43115-4_9
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DOI: https://doi.org/10.1007/978-3-319-43115-4_9
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