Join Us | Latest Articles | Contact

Journal Home

Editorial Board


Submit to this journal

Current issue

International Journal of Cancer and Clinical Research

DOI: 10.23937/2378-3419/1/1/1007

Epidemiology and Radiotherapy of Hepatocellular Carcinoma

Rex Cheung *

Flushing Radiation Oncology CyberKnife Center, USA

*Corresponding author: Rex Cheung, Flushing Radiation Oncology CyberKnife Center, 40-20 Main Street, 4th Floor, Flushing, NY 11354, USA, E-mail:
Int J Cancer Clin Res, IJCCR-1-007, (Volume 1, Issue 1), Short Communication; ISSN: 2378-3419
Received: September 10, 2014 | Accepted: October 24, 2014 | Published: October 27, 2014
Citation: Cheung R (2014) Epidemiology and Radiotherapy of Hepatocellular Carcinoma. Int J Cancer Clin Res 1:007. 10.23937/2378-3419/1/1/1007
Copyright: © 2014 Cheung R. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Hepatocellular cancer, Epidemiology, Stereotactic, Radiotherapy, Socioeconomic factors


Hepatocellular carcinoma (HCC) is a primary liver cancer secondary to chronic liver conditions such as hepatitis Bvirus (HBV) and C virus (HCV) infections, obesity and alcoholism [1-3]. HCC is the sixth most common solid tumor, and third most lethal cancer globally [2]. There may be a gender difference in the development and outcome of chronic liver diseases [4]. In U.S., the incidence of HBV infection has declined since the introduction of HBV vaccination in 1981 [5]. But approximately 350 million of global population has chronic HBV infection [6]. Hepatitis C virus (HCV) infection is another major source of chronic liver disease and cirrhosis [2]. About 3 % of world population are infected with HCV [7]. About 20-30% of HCV patients developed cirrhosis after 2-3 decades [7]. Overall, once cirrhosis developed, the incidence of HCC development is 3-4% per year [2]. More than 80 % of HCC develops from a cirrhotic liver [2]. The incidence of HCC is rising globally especially in the developing Asian and African countries [1,8]. This paper is a part of a series focusing on using advanced stereotactic radiotherapy in challenging oncologic scenario [9].

Treatment of Hepatocellular Carcinoma

Staging of HCC is based on Barcelona Clinic Liver Cancer (BCLC) staging system. HCC progresses from stage A to D based on the number of nodules, size, performance status of the patient (symptomatic or not), vascular invasion and extrahepatic spread [2]. Asymptomatic small HCC with good liver function has a cure rate of about 70% [2]. But most HCC (60-70%) are diagnosed at an advanced stage [2]. Development of the first oral agent Sarofenib (Nexavar), a multitargeted tyrosine kinase inhibitor has a small but significant improvement in the survival of advanced stage HCC with good liver function [2].

Treatment of earlier stage HCC includes liver transplant [1], surgical resection, transarterial chemoembolization (TACE), radiofreqencyablation (RFA), and radiotherapy [10-14]. Child-Pugh (CP) liver functional statustakes into account five clinical measures total bilirubin, serum albumin, prothrombin time (PT) international normalized ratio (INR), ascites, hepatic encephalopathy. CP score and BCLC stage are important factorsin selecting curative versus non-curative treatment for HCC patients [2].

Public Health Aspects of Hepatocellular Carcinoma

Prevention of HCC may depend on removing the underlying major risk factors of HCC [15]. For example controllingcurrent obesity epidemic may reduce the risk of Non-alcoholic Fatty Liver Disease (NAFLD) and its most severe form Non-Alcoholic Steato Hepatitis (NASH) and the subsequent development of HCC [15]. HCC is the first human tumor that is amenable to prevention by HBV vaccination [15]. In Taiwan, mass HBV vaccination has led to a decrease in childhood HCC [15]. And the global burden of chronic HBV infection has also decreased because of mass vaccination since early 1980as a child may prevent this [15]. However, HBV vaccination may not be available in some developing countries. In Canada, it has been found that it is cost effective to screen and vaccinate their newly arrived immigrants [6]. Screening for HCV infection may also be cost effective [16]. Although there is no currently no HCV vaccine available [16]. HCC surveillance by liver ultrasound every 6 months may be cost effective in detecting HCC early in high-risk population [17,18]. Early detection of HCC may increase the likelihood of having curative and effective treatments [17].

In U.S., Center of Disease Control (CDC) National Health and Nutrition, Examination and Survey (NHANES) collected data of HBV and HCVinfection and their other health variables including mortality data [19,20]. National Cancer Institute (NCI) Surveillance, End Results and Epidemiology (SEER) project also collects treatment and outcome data on HCC [10]. These are valuable sources of data available for public health research in this area.

Radiotherapy for HCC

Radiotherapy has become important in the treatment of HCC as a bridge to transplant and for palliation, especially stereotactic body radiotherapy (SBRT) and proton beam radiotherapy (RT) are considered effective treatments [13,21,22]. RT is particularly useful for HCC patients with venous thrombosis that may be a contraindication for other local therapies [23-25]. The local control rate could be as high a 90% for small HCC less than 3 cm [26]. Local control of HCC has been associated with improved survival [12,27]. Local therapy has been found to been useful for patients to meet the Milan Criteria (HCC < 5 cm, or up to 3 HCC, each < 3 cm) on transplant list for more than 6 months [26,28]. But it may be controversial for patients on a shorter waiting list for liver transplant [26].

Advanced radiotherapy technology is critical in the success of radiation treatment of HCC [13,29-31]. However, most of the hospitals in the countries where HCC is most prevalent may not have the appropriate technology to deliver good radiotherapy for HCC patients [32]. Even in advanced countries such as U.S. socio-economic factors could still be a barrier to access to these advanced technologies. Studies related to the socio-economic barriers facing HCC patients may help to solve these problems and help them achieve best and most cost effective radiation treatment outcome.

  1. Hertl M, Cosimi AB (2005) Liver transplantation for malignancy. Oncologist 10: 269-281.

  2. Barone C, Koeberle D, Metselaar H, Parisi G, Sansonno D, et al. (2013) Multidisciplinary approach for HCC patients: hepatology for the oncologists. Ann Oncol 24 Suppl 2: ii15-23.

  3. Karagozian R, Derdák Z2, Baffy G3 (2014) Obesity-associated mechanisms of hepatocarcinogenesis. Metabolism 63: 607-617.

  4. Guy J, Peters MG (2013) Liver disease in women: the influence of gender on epidemiology, natural history, and patient outcomes. Gastroenterol Hepatol (N Y) 9: 633-639.

  5. Chao DC, Hu KQ (2013) Update on rescue therapies in patients with lamivudine-resistant chronic hepatitis B. Drug Des Devel Ther 7: 777-788.

  6. Rossi C, Schwartzman K, Oxlade O, Klein MB, Greenaway C (2013) Hepatitis B screening and vaccination strategies for newly arrived adult Canadian immigrants and refugees: a cost-effectiveness analysis. PLoS One 8: e78548.

  7. Lee MH, Yang HI, Yuan Y, L'Italien G, Chen CJ (2014) Epidemiology and natural history of hepatitis C virus infection. World J Gastroenterol 20: 9270-9280.

  8. Norsa'adah B, Nurhazalini-Zayani CG (2013) Epidemiology and survival of hepatocellular carcinoma in north-east Peninsular Malaysia. Asian Pac J Cancer Prev 14: 6955-6959.

  9. Cheung R (2014) Using a Robotic Stereotactic Radiation Treatment System to Treat Benign Intracranial Tumors and Trigeminal Neuralgia. Austin J Radiat Oncol & Cancer 1: 2.

  10. Shaya FT, Breunig IM, Seal B, Mullins CD, Chirikov VV, et al. (2014) Comparative and cost effectiveness of treatment modalities for hepatocellular carcinoma in SEER-Medicare. Pharmacoeconomics 32: 63-74.

  11. Yu JI, Park HC, Lim do H, Kim CJ, Oh D, et al. (2012) Scheduled interval trans-catheter arterial chemoembolization followed by radiation therapy in patients with unresectable hepatocellular carcinoma. J Korean Med Sci 27: 736-743.

  12. Jang WI, Kim MS, Bae SH, Cho CK, Yoo HJ, et al. (2013) High-dose stereotactic body radiotherapy correlates increased local control and overall survival in patients with inoperable hepatocellular carcinoma. Radiat Oncol 8: 250.

  13. Kawashima M, Kohno R, Nakachi K, Nishio T, Mitsunaga S, et al. (2011) Dose-volume histogram analysis of the safety of proton beam therapy for unresectable hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 79: 1479-1486.

  14. Cucchetti A, Piscaglia F, Cescon M, Ercolani G, Pinna AD (2013) Systematic review of surgical resection vs radiofrequency ablation for hepatocellular carcinoma. World J Gastroenterol 19: 4106-4118.

  15. Gomaa AI, Khan SA, Toledano MB, Waked I, Taylor-Robinson SD (2008) Hepatocellular carcinoma: epidemiology, risk factors and pathogenesis. World J Gastroenterol 14: 4300-4308.

  16. Ansaldi F, Orsi A, Sticchi L, Bruzzone B, Icardi G (2014) Hepatitis C virus in the new era: perspectives in epidemiology, prevention, diagnostics and predictors of response to therapy. World J Gastroenterol 20: 9633-9652.

  17. Giannini EG, Cucchetti A, Erroi V, Garuti F, Odaldi F, et al. (2013) Surveillance for early diagnosis of hepatocellular carcinoma: how best to do it? World J Gastroenterol 19: 8808-8821.

  18. van Meer S, de Man RA, Siersema PD, van Erpecum KJ (2013) Surveillance for hepatocellular carcinoma in chronic liver disease: evidence and controversies. World J Gastroenterol 19: 6744-6756.

  19. Denniston MM, Jiles RB, Drobeniuc J, Klevens RM, Ward JW, et al. (2014) Chronic hepatitis C virus infection in the United States, National Health and Nutrition Examination Survey 2003 to 2010. Ann Intern Med 160: 293-300.

  20. Jinjuvadia R, Liangpunsakul S, Antaki F (2014) Past exposure to hepatitis B: a risk factor for increase in mortality? J Clin Gastroenterol 48: 267-271.

  21. Bibault JE, Dewas S, Vautravers-Dewas C, Hollebecque A, Jarraya H, et al. (2013) Stereotactic body radiation therapy for hepatocellular carcinoma: prognostic factors of local control, overall survival, and toxicity. PLoS One 8: e77472.

  22. Hata M, Tokuuye K, Sugahara S, Fukumitsu N, Hashimoto T, et al. (2006) Proton beam therapy for hepatocellular carcinoma patients with severe cirrhosis. Strahlenther Onkol 182: 713-720.

  23. Igaki H, Nakagawa K, Shiraishi K, Shiina S, Kokudo N, et al. (2008) Three-dimensional conformal radiotherapy for hepatocellular carcinoma with inferior vena cava invasion. Jpn J Clin Oncol 38: 438-444.

  24. Lin CS, Jen YM, Chiu SY, Hwang JM, Chao HL, et al. (2006) Treatment of portal vein tumor thrombosis of hepatoma patients with either stereotactic radiotherapy or three-dimensional conformal radiotherapy. Jpn J Clin Oncol 36: 212-217.

  25. Yu JI, Park HC, Lim do H, Park W, Yoo BC, et al. (2011) Prognostic index for portal vein tumor thrombosis in patients with hepatocellular carcinoma treated with radiation therapy. J Korean Med Sci 26: 1014-1022.

  26. Sourianarayanane A, El-Gazzaz G, Sanabria JR, Menon KV, Quintini C, et al. (2012) Loco-regional therapy in patients with Milan Criteria-compliant hepatocellular carcinoma and short waitlist time to transplant: an outcome analysis. HPB (Oxford) 14: 325-332.

  27. Memon K, Kulik L, Lewandowski RJ, Wang E, Riaz A, et al. (2011) Radiographic response to locoregional therapy in hepatocellular carcinoma predicts patient survival times. Gastroenterology 141: 526-535, 535.

  28. Pompili M, Francica G, Ponziani FR, Iezzi R, Avolio AW (2013) Bridging and downstaging treatments for hepatocellular carcinoma in patients on the waiting list for liver transplantation. World J Gastroenterol 19: 7515-7530.

  29. Park JM, Kim K, Chie EK, Choi CH, Ye SJ, et al. (2012) RapidArc vs intensity-modulated radiation therapy for hepatocellular carcinoma: a comparative planning study. Br J Radiol 85: e323-329.

  30. Wang PM, Hsu WC, Chung NN, Chang FL, Fogliata A, et al. (2012) Radiation treatment with volumetric modulated arc therapy of hepatocellular carcinoma patients. Early clinical outcome and toxicity profile from a retrospective analysis of 138 patients. Radiat Oncol 7: 207.

  31. Yoon SM, Lim YS, Park MJ, Kim SY, Cho B, et al. (2013) Stereotactic body radiation therapy as an alternative treatment for small hepatocellular carcinoma. PLoS One 8: e79854.

  32. Poon D, Anderson BO, Chen LT, Tanaka K, Lau WY, et al. (2009) Management of hepatocellular carcinoma in Asia: consensus statement from the Asian Oncology Summit 2009. Lancet Oncol 10: 1111-1118.

International Journal of Anesthetics and Anesthesiology (ISSN: 2377-4630)
International Journal of Blood Research and Disorders   (ISSN: 2469-5696)
International Journal of Brain Disorders and Treatment (ISSN: 2469-5866)
International Journal of Cancer and Clinical Research (ISSN: 2378-3419)
International Journal of Clinical Cardiology (ISSN: 2469-5696)
Journal of Clinical Gastroenterology and Treatment (ISSN: 2469-584X)
Clinical Medical Reviews and Case Reports (ISSN: 2378-3656)
Journal of Dermatology Research and Therapy (ISSN: 2469-5750)
International Journal of Diabetes and Clinical Research (ISSN: 2377-3634)
Journal of Family Medicine and Disease Prevention (ISSN: 2469-5793)
Journal of Genetics and Genome Research (ISSN: 2378-3648)
Journal of Geriatric Medicine and Gerontology (ISSN: 2469-5858)
International Journal of Immunology and Immunotherapy (ISSN: 2378-3672)
International Journal of Medical Nano Research (ISSN: 2378-3664)
International Journal of Neurology and Neurotherapy (ISSN: 2378-3001)
International Archives of Nursing and Health Care (ISSN: 2469-5823)
International Journal of Ophthalmology and Clinical Research (ISSN: 2378-346X)
International Journal of Oral and Dental Health (ISSN: 2469-5734)
International Journal of Pathology and Clinical Research (ISSN: 2469-5807)
International Journal of Pediatric Research (ISSN: 2469-5769)
International Journal of Respiratory and Pulmonary Medicine (ISSN: 2378-3516)
Journal of Rheumatic Diseases and Treatment (ISSN: 2469-5726)
International Journal of Sports and Exercise Medicine (ISSN: 2469-5718)
International Journal of Stem Cell Research & Therapy (ISSN: 2469-570X)
International Journal of Surgery Research and Practice (ISSN: 2378-3397)
Trauma Cases and Reviews (ISSN: 2469-5777)
International Archives of Urology and Complications (ISSN: 2469-5742)
International Journal of Virology and AIDS (ISSN: 2469-567X)
More Journals

Contact Us

ClinMed International Library | Science Resource Online LLC
3511 Silverside Road, Suite 105, Wilmington, DE 19810, USA


Get Email alerts
Creative Commons License
Open Access
by ClinMed International Library is licensed under a Creative Commons Attribution 4.0 International License based on a work at
Copyright © 2017 ClinMed International Library. All Rights Reserved.