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Primary liver cancer is cancer that forms in the tissues of the liver. Secondary liver cancer is cancer that spreads to the liver from another part of the body. Learn about liver cancer and find information on how we support and care for people with liver cancer before, during, and after treatment.
At the Center for Gastrointestinal Oncology, we view every patient as an individual, with unique needs and expectations. This understanding guides us in creating a tailored, personalized treatment plan that takes your lifestyle and goals into account.
Our team of specialists includes medical oncologists, surgeons, and radiation oncologists who focus exclusively on gastrointestinal cancers, including colon cancer, pancreatic cancer, stomach cancer, liver cancer, neuroendocrine cancer, thyroid cancer, and esophageal cancer.
We offer the most advanced treatments for gastrointestinal cancers, including access to clinical trials. As a new patient, you'll have your tumors tested for molecular alterations, the results of which will help form the basis of your therapy.
We understand that cancer treatment can be challenging both physically and emotionally. Our patients, and their families, have access to a range of support services, including nutrition counseling, rehabilitation and physical therapy, support groups, and complementary therapies such as acupuncture and massage.Learn more about treatment and support for patients with gastrointestinal cancer
Our clinicians are experts in treating all types of gastrointestinal cancers, including:
If you have never been seen before at Dana-Farber/Brigham and Women's Cancer Center, please call 877-442-3324 or use this online form to make an appointment.
If you are a current patient, please call the center’s main number at 617-632-4500.
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Mailing addressCenter for Gastrointestinal OncologyDana-Farber Cancer Institute450 Brookline Ave.Boston, MA 02215-5450
The liver is one of the largest organs in the body. It has four lobes and fills the upper right side of the abdomen inside the rib cage. Three of the many important functions of the liver are:
The two types of adult primary liver cancer are:
The most common type of adult primary liver cancer is hepatocellular carcinoma.
This summary refers to the treatment of primary liver cancer (cancer that begins in the liver). Treatment of cancer that begins in other parts of the body and spreads to the liver is not discussed in this summary.
Primary liver cancer can occur in both adults and children. However, treatment for children is different than treatment for adults. (See the PDQ summary on Childhood Liver Cancer Treatment for more information.)
Anything that increases your chance of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn’t mean that you will not get cancer. Talk with your doctor if you think you may be at risk. The following are risk factors for adult primary liver cancer:
These and other signs and symptoms may be caused by adult primary liver cancer or by other conditions. Check with your doctor if you have any of the following:
The following tests and procedures may be used:
A biopsy is not always needed to diagnose adult primary liver cancer.
The prognosis (chance of recovery) and treatment options depend on the following:
The process used to find out if cancer has spread within the liver or to other parts of the body is called staging. The information gathered from the staging process determines the stage of the disease. It is important to know the stage in order to plan treatment. The following tests and procedures may be used in the staging process:
Cancer can spread through tissue, the lymph system, and the blood:
When cancer spreads to another part of the body, it is called metastasis. Cancer cells break away from where they began (the primary tumor) and travel through the lymph system or blood.
The metastatic tumor is the same type of cancer as the primary tumor. For example, if primary liver cancer spreads to the lung, the cancer cells in the lung are actually liver cancer cells. The disease is metastatic liver cancer, not lung cancer.
There are several staging systems for liver cancer. The Barcelona Clinic Liver Cancer (BCLC) Staging System is widely used and is described below. This system is used to predict the patient's chance of recovery and to plan treatment, based on the following:
The BCLC staging system has five stages:
Treatment to cure the cancer is given for BCLC stages 0, A, and B.
Treatment to relieve the symptoms caused by liver cancer and improve the patient's quality of life is given for BCLC stages C and D. Treatments are not likely to cure the cancer.
Different types of treatments are available for patients with adult primaryliver cancer. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.
A partial hepatectomy(surgery to remove the part of the liver where cancer is found) may be done. A wedge of tissue, an entire lobe, or a larger portion of the liver, along with some of the healthy tissue around it is removed. The remaining liver tissue takes over the functions of the liver and may regrow.
In a liver transplant, the entire liver is removed and replaced with a healthy donated liver. A liver transplant may be done when the disease is in the liver only and a donated liver can be found. If the patient has to wait for a donated liver, other treatment is given as needed.
Ablationtherapy removes or destroys tissue. Different types of ablation therapy are used for liver cancer:
Embolization therapy is the use of substances to block or decrease the flow of blood through the hepatic artery to the tumor. When the tumor does not get the oxygen and nutrients it needs, it will not continue to grow. Embolization therapy is used for patients who cannot have surgery to remove the tumor or ablation therapy and whose tumor has not spread outside the liver.
The liver receives blood from the hepatic portal vein and the hepatic artery. Blood that comes into the liver from the hepatic portal vein usually goes to the healthy liver tissue. Blood that comes from the hepatic artery usually goes to the tumor. When the hepatic artery is blocked during embolization therapy, the healthy liver tissue continues to receive blood from the hepatic portal vein.
There are two main types of embolization therapy:
Targeted therapy is a treatment that uses drugs or other substances to identify and attack specific cancer cells without harming normal cells. Adult liver cancer may be treated with a targeted therapy drug that stops cells from dividing and prevents the growth of new blood vessels that tumors need to grow.
See Drugs Approved for Liver Cancer for more information.
Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. Radiation therapy is given in different ways:
Information about clinical trials is available from the NCI Web site.
For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.
Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.
Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.
Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.
Clinical trials are taking place in many parts of the country. See the Treatment Options section that follows for links to current treatment clinical trials. These have been retrieved from NCI's listing of clinical trials.
Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests. This is sometimes called re-staging.
Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.
Treatment of stages 0, A, and B adult primaryliver cancer may include the following:
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage 0 adult primary liver cancer (BCLC), stage A adult primary liver cancer (BCLC) and stage B adult primary liver cancer (BCLC). For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.
Treatment of stages C and D adult primaryliver cancer may include the following:
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage C adult primary liver cancer (BCLC) and stage D adult primary liver cancer (BCLC). For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.
For more information from the National Cancer Institute about adult primary liver cancer, see the following:
For general cancer information and other resources from the National Cancer Institute, see the following:
This information is provided by the National Cancer Institute.
This information was last updated on June 26, 2014.
Estimated new cases and deaths from liver and intrahepatic bile duct cancer in the United States in 2014:
Hepatocellular carcinoma (HCC) is relatively uncommon in the United
States, although its incidence is rising, principally in relation to the spread
of hepatitis C virus (HCV) infection. HCC is the most common solid tumor worldwide and the third leading cause of cancer-related deaths.
Both local extension of tumor and extent of liver function impairment affect prognosis and guide selection of treatment. Liver transplantation, surgical resection, and ablation techniques offer high rates of complete responses, and a potential for cure in early HCC. There are no large, robust, randomized studies that compare treatments considered effective for early stage disease, nor are there studies comparing these treatments with best supportive care. Best survivals are achieved when the HCC can be surgically excised (either by a transplantation or resection).
For patients with decompensated cirrhosis and a solitary lesion (<5 cm) or early multifocal disease (≤3 lesions, ≤3 cm), the best option is liver transplantation, but the limited availability of deceased liver donors restricts the use of this approach.
Surgical resection is usually performed in patients with localized HCC and sufficient functional hepatic reserve.
Among noncurative treatment for HCC, transarterial chemoembolization and sorafenib have been shown to improve survival.
The etiology of HCC is likely multifactorial. Any chronic liver injury probably increases the risk of HCC. This risk seems elevated especially in patients who develop cirrhosis. The 5-year cumulative
risk of developing HCC for patients with cirrhosis ranges between 5% and 30% and depends on etiology (highest in individuals with HCV infection), region or ethnicity (highest in Asians), and stage of cirrhosis.[Level of evidence: 3iii]
Hepatitis B virus (HBV) infection and HCV infection appear to be the most significant causes of HCC worldwide. Chronic HBV infection is the leading cause of HCC in Asia and Africa, and HCV infection is the leading cause of HCC in Europe, Japan, and North America.
The annual incidence of HCC in HBV carriers is 0.5% to 1% per year in noncirrhotic patients and 2.5% per year in cirrhotic patients. The relative risk of HCC is 100 (i.e., HBV carriers are 100 times more likely to develop HCC than uninfected persons).
In a single, prospective, population-based study that included 12,008 patients, the presence of anti-HCV positivity conferred a twentyfold increased risk of HCC compared with anti-HCV negative persons. HCC may occur in HCV-infected patients with bridging fibrosis even in the absence of overt cirrhosis. However, the risk is highest among those patients with HCV-related established cirrhosis, which has an incidence rate of HCC of 2% to 8% per year.
Several reports suggest that alcoholic cirrhosis is a risk factor for HCC. However, the true incidence of HCC in alcoholic cirrhosis is unknown because most epidemiology reports on this subject were published before the identification of hepatitis C virus.
Recently, the risk factors associated with the metabolic syndrome, including insulin resistance, hypertension, dyslipidemia, and obesity have been recognized as potential causes of nonalcoholic hepatosteatosis, cirrhosis, and HCC. However, no study to date has followed a sufficiently large group of these patients for long enough to describe an incidence rate for HCC.
Hemochromatosis is also a significant risk factor for HCC and has an increased relative risk twenty times that of the normal population.
The incidence of HCC in stage IV primary biliary cirrhosis is approximately the same as in cirrhosis resulting from hepatitis C.
Aflatoxin B1 is produced by fungi of the Aspergillus species and is a common contaminant of grain, nuts, and vegetables in some parts of Asia and Africa. Aflatoxin B1 has also been implicated as a cofactor in the etiology of primary liver cancer in HBV carriers because it enhances the neoplastic risk threefold.
(Refer to the PDQ summary on Liver (Hepatocellular) Cancer Screening for more information.)
For lesions that are smaller than 1 cm and are detected during screening in patients at high risk for HCC, no detailed investigation is required because most of these lesions will be cirrhotic nodules rather than HCC.[Level of evidence: 3iii] Close follow-up at 3-month intervals is recommended using the same technique that first documented the presence of the nodules.
For patients with liver nodules larger than 1 cm who are at risk for HCC, diagnosis should be established. The tests required to diagnose HCC may include radiology, biopsy, or both.
AFP is insufficiently sensitive or specific for use as a diagnostic assay.
AFP can be elevated in intrahepatic cholangiocarcinoma and in some metastases from colon cancer. The finding of a mass in a liver with an elevated AFP does not automatically indicate HCC. If the AFP level is high, it can be used to monitor for recurrence.
In patients with cirrhosis, liver disease, or other risk factors for HCC, triple-phase, contrast-enhanced studies (dynamic computed tomography [CT]-scan or magnetic resonance imaging [MRI]) can be used to establish diagnosis of HCC for nodules larger than 1 cm.
During the arterial phase of the study, HCC enhances more intensely than the surrounding liver because the arterial blood in the liver is diluted by venous blood that does not contain contrast, whereas the HCC contains only arterial blood. In the venous phase, the HCC enhances less than the surrounding liver, which is referred to as the venous washout of HCC, because the arterial blood flowing through the lesion no longer contains contrast; however, the portal blood in the liver now contains contrast.
The presence of arterial uptake followed by washout in a single dynamic study is highly specific (95%–100%) for an HCC of 1 to 3 cm in diameter and virtually diagnostic of HCC.[Level of evidence: 3ii] In these cases, the diagnosis of HCC may be considered established without the need for a second imaging modality, even in the absence of a biopsy confirmation.[Level of evidence: 3ii]
If, on the other hand, a first imaging modality, such as either a contrast-enhanced CT or MRI, is not conclusive, sequential imaging with a different modality can improve sensitivity for HCC detection (from 33% to 41% for either CT or MRI to 76% for both studies when performed sequentially) without a decrease in specificity.
If, despite the use of two imaging modalities, a nodule larger than 1 cm remains uncharacterized in a patient at high risk for HCC (i.e., with only one or no classic enhancement pattern), a liver biopsy can be considered.
A liver biopsy may be performed when a diagnosis of HCC is not established by a dynamic imaging modality (three-phase CT or MRI) for liver nodules 1 cm or larger in high-risk patients.
The natural history of early tumors is poorly known because the majority of patients are treated. However, older reports have described 3-year survival rates of 13% to 21% without any specific treatment. At present, only 10% to 23% of HCC patients may be surgical candidates for curative-intent treatment. The 5-year overall survival rates for patients with early HCC who are undergoing liver transplant or liver resection are 44% to 78% and 27% to 70%, respectively.
The natural course of advanced-stage HCC is better known. Untreated patients with advanced disease usually survive less than 6 months. The 1-year and 2-year survival rates of untreated patients in 25 randomized clinical trials were 10% to 72% and 8% to 50%, respectively.
Unlike most patients with solid tumors, prognosis of HCC patients is affected not only by the tumor stage at presentation but also by the underlying liver function.
The following are main prognostic factors for HCC patients:
Other PDQ summaries containing information related to adult primary liver cancer include the following:
American Cancer Society: Cancer Facts and Figures 2014. Atlanta, Ga: American Cancer Society, 2014. Available online. Last accessed May 21, 2014.
Altekruse SF, McGlynn KA, Reichman ME: Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J Clin Oncol 27 (9): 1485-91, 2009.
Llovet JM, Burroughs A, Bruix J: Hepatocellular carcinoma. Lancet 362 (9399): 1907-17, 2003.
Bosch FX, Ribes J, Díaz M, et al.: Primary liver cancer: worldwide incidence and trends. Gastroenterology 127 (5 Suppl 1): S5-S16, 2004.
Bruix J, Sherman M; American Association for the Study of Liver Diseases: Management of hepatocellular carcinoma: an update. Hepatology 53 (3): 1020-2, 2011.
Llovet JM, Ricci S, Mazzaferro V, et al.: Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359 (4): 378-90, 2008.
Llovet JM, Bruix J: Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival. Hepatology 37 (2): 429-42, 2003.
Cammà C, Schepis F, Orlando A, et al.: Transarterial chemoembolization for unresectable hepatocellular carcinoma: meta-analysis of randomized controlled trials. Radiology 224 (1): 47-54, 2002.
Fattovich G, Giustina G, Schalm SW, et al.: Occurrence of hepatocellular carcinoma and decompensation in western European patients with cirrhosis type B. The EUROHEP Study Group on Hepatitis B Virus and Cirrhosis. Hepatology 21 (1): 77-82, 1995.
Mair RD, Valenzuela A, Ha NB, et al.: Incidence of hepatocellular carcinoma among US patients with cirrhosis of viral or nonviral etiologies. Clin Gastroenterol Hepatol 10 (12): 1412-7, 2012.
Bosch FX, Ribes J, Borràs J: Epidemiology of primary liver cancer. Semin Liver Dis 19 (3): 271-85, 1999.
Beasley RP, Hwang LY, Lin CC, et al.: Hepatocellular carcinoma and hepatitis B virus. A prospective study of 22 707 men in Taiwan. Lancet 2 (8256): 1129-33, 1981.
Beasley RP: Hepatitis B virus. The major etiology of hepatocellular carcinoma. Cancer 61 (10): 1942-56, 1988.
Sun CA, Wu DM, Lin CC, et al.: Incidence and cofactors of hepatitis C virus-related hepatocellular carcinoma: a prospective study of 12,008 men in Taiwan. Am J Epidemiol 157 (8): 674-82, 2003.
Lok AS, Seeff LB, Morgan TR, et al.: Incidence of hepatocellular carcinoma and associated risk factors in hepatitis C-related advanced liver disease. Gastroenterology 136 (1): 138-48, 2009.
Jaskiewicz K, Banach L, Lancaster E: Hepatic siderosis, fibrosis and cirrhosis: the association with hepatocellular carcinoma in high-risk population. Anticancer Res 17 (5B): 3897-9, 1997 Sep-Oct.
Farinati F, Floreani A, De Maria N, et al.: Hepatocellular carcinoma in primary biliary cirrhosis. J Hepatol 21 (3): 315-6, 1994.
Sun Z, Lu P, Gail MH, et al.: Increased risk of hepatocellular carcinoma in male hepatitis B surface antigen carriers with chronic hepatitis who have detectable urinary aflatoxin metabolite M1. Hepatology 30 (2): 379-83, 1999.
Furuya K, Nakamura M, Yamamoto Y, et al.: Macroregenerative nodule of the liver. A clinicopathologic study of 345 autopsy cases of chronic liver disease. Cancer 61 (1): 99-105, 1988.
Leoni S, Piscaglia F, Golfieri R, et al.: The impact of vascular and nonvascular findings on the noninvasive diagnosis of small hepatocellular carcinoma based on the EASL and AASLD criteria. Am J Gastroenterol 105 (3): 599-609, 2010.
Khalili K, Kim TK, Jang HJ, et al.: Optimization of imaging diagnosis of 1-2 cm hepatocellular carcinoma: an analysis of diagnostic performance and resource utilization. J Hepatol 54 (4): 723-8, 2011.
Sangiovanni A, Manini MA, Iavarone M, et al.: The diagnostic and economic impact of contrast imaging techniques in the diagnosis of small hepatocellular carcinoma in cirrhosis. Gut 59 (5): 638-44, 2010.
Khalili K, Kim TK, Jang HJ, et al.: Implementation of AASLD hepatocellular carcinoma practice guidelines in North America: two years of experience. [Abstract] Hepatology 48 (Suppl 1): A-128, 362A, 2008.
Barbara L, Benzi G, Gaiani S, et al.: Natural history of small untreated hepatocellular carcinoma in cirrhosis: a multivariate analysis of prognostic factors of tumor growth rate and patient survival. Hepatology 16 (1): 132-7, 1992.
Ebara M, Ohto M, Shinagawa T, et al.: Natural history of minute hepatocellular carcinoma smaller than three centimeters complicating cirrhosis. A study in 22 patients. Gastroenterology 90 (2): 289-98, 1986.
Shah SA, Smith JK, Li Y, et al.: Underutilization of therapy for hepatocellular carcinoma in the medicare population. Cancer 117 (5): 1019-26, 2011.
Sonnenday CJ, Dimick JB, Schulick RD, et al.: Racial and geographic disparities in the utilization of surgical therapy for hepatocellular carcinoma. J Gastrointest Surg 11 (12): 1636-46; discussion 1646, 2007.
Dhir M, Lyden ER, Smith LM, et al.: Comparison of outcomes of transplantation and resection in patients with early hepatocellular carcinoma: a meta-analysis. HPB (Oxford) 14 (9): 635-45, 2012.
Okuda K, Ohtsuki T, Obata H, et al.: Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Study of 850 patients. Cancer 56 (4): 918-28, 1985.
Llovet JM, Brú C, Bruix J: Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis 19 (3): 329-38, 1999.
A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients: the Cancer of the Liver Italian Program (CLIP) investigators. Hepatology 28 (3): 751-5, 1998.
Malignant primary tumors of the liver consist of two major cell types: hepatocellular, which accounts for 90% of cases, and cholangiocarcinoma.
Histologic classification is as follows:
Hepatoblastoma rarely occurs in adults.
Mavros MN, Mayo SC, Hyder O, et al.: A systematic review: treatment and prognosis of patients with fibrolamellar hepatocellular carcinoma. J Am Coll Surg 215 (6): 820-30, 2012.
Prognostic modeling in hepatocellular carcinoma (HCC) is complex because variables of two diseases--cirrhosis and cancer--are involved in as many as 80% of the cases. Tumor features and the factors related to functional hepatic reserve must be taken into account. The key prognostic factors are only partially known and vary at different stages of the disease. More than ten classifications are used throughout the world, but no system is accepted worldwide.
The TNM classification for staging, proposed by the AJCC, is not widely utilized. Clinical use of TNM staging is limited because liver function is not considered. It is also difficult to use this system to select treatment options because TNM staging relies on detailed histopathological
examination available only after excision. TNM may be useful in prognostic prediction after liver resection.
The AJCC has designated staging by TNM to define
Primary tumor cannot be assessed.
No evidence of primary tumor.
Solitary tumor without vascular invasion.
Solitary tumor with vascular invasion or multiple tumors none >5 cm.
Multiple tumors >5 cm.
Single tumor or multiple tumors of any size involving a major branch of the portal vein or hepatic vein.
Tumor(s) with direct invasion of adjacent organs other than the gallbladder or with perforation of visceral peritoneum.
aReprinted with permission from AJCC: Liver. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual, 7th ed. New York, NY: Springer, 2010, pp 191-9.
Regional lymph nodes cannot be assessed.
No regional lymph node metastasis.
Regional lymph node metastasis.
No distant metastasis.
The Okuda staging system includes variables related to tumor burden and liver function, such as bilirubin, albumin, and ascites and has been extensively used in the past. However, many significant prognostic tumor factors confirmed in both surgical and nonsurgical series (e.g., unifocal or multifocal, vascular invasion, portal venous thrombosis, or locoregional lymph node involvement) are not included. As a result, Okuda staging is unable to stratify prognosis for early-stage cancers and mostly serves to recognize end-stage cancer patients.
New classifications have been proposed in an effort to overcome the difficulties of having several staging systems. The BCLC staging classification retains its usefulness in early tumors and is currently the most accepted staging system for HCC. Recent evidence from an American cohort has shown that BCLC staging offers better prognostic stratification power than other staging systems.
The BCLC staging system attempts to overcome the limitations of previous staging systems by including variables related to the following:
Five stages (0 and A through D) are identified based on the variables mentioned above. Of note, the BCLC staging system links each HCC stage to appropriate treatment modalities. According to the BCLC, patients with early-stage HCC may benefit from curative therapies (i.e., liver transplantation, surgical resection, and radiofrequency ablation techniques); those at intermediate- or advanced-disease stage may benefit from palliative treatments (i.e., transcatheter arterial chemoembolization and sorafenib); however, those at end-stage disease who have a very poor life expectancy are offered supportive care and palliation.
Liver. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 191-5.
Poon RT, Ng IO, Fan ST, et al.: Clinicopathologic features of long-term survivors and disease-free survivors after resection of hepatocellular carcinoma: a study of a prospective cohort. J Clin Oncol 19 (12): 3037-44, 2001.
Pompili M, Rapaccini GL, Covino M, et al.: Prognostic factors for survival in patients with compensated cirrhosis and small hepatocellular carcinoma after percutaneous ethanol injection therapy. Cancer 92 (1): 126-35, 2001.
Marrero JA, Fontana RJ, Barrat A, et al.: Prognosis of hepatocellular carcinoma: comparison of 7 staging systems in an American cohort. Hepatology 41 (4): 707-16, 2005.
There is no worldwide agreement on a common treatment strategy for patients with hepatocellular carcinoma (HCC). Several treatments for HCC are available that are associated with long-term survival, including liver transplantation, surgical resection, and ablation techniques.
Selection of treatment is complex because several factors related to the underlying liver function, the extent and location of the tumor, and the general condition of the patient must be considered. Often, patients with HCC are evaluated by a multidisciplinary team including hepatologists, radiologists, interventional radiologists, radiation oncologists, transplant surgeons, surgical oncologists, pathologists, and medical oncologists.
From a treatment perspective, HCC can be divided into the following two broad categories:
Localized hepatocellular carcinomas (HCCs) that present either as a solitary mass in a portion of the liver or as a limited number of tumors (three nodules, each <3 cm in diameter) without major vascular invasion constitute approximately 30% of the HCC cases. The three potentially curative therapies (i.e., liver transplantation, surgical resection, and ablation techniques) are acceptable treatment options for small, single-nodule HCC in patients with well-preserved liver function. Surgery is the mainstay of HCC treatment. Resection and transplantation achieve the best outcomes in well-selected candidates and are usually considered to be the first option for curative intent.
Liver transplantation is a potentially curative therapy for HCC and has the benefit of treating the underlying cirrhosis, but the scarcity of organ donors limits the availability of this treatment modality.
Liver transplantation is determined by the Milan criteria, which is defined as a single HCC lesion smaller than 5 cm, or 2 to 3 nodules smaller than 3 cm. Expansion of the accepted transplantation for HCC is not supported by consistent data.
Liver transplantation is considered if resection is precluded as a result of multiple, small, tumor nodules (≤3 nodules, each <3 cm), or if the liver function is impaired (Child-Pugh B and C class). In those patients, transplantation is associated with a 5-year overall survival (OS) rate of approximately 70%.[Level of evidence: 3iii]
Surgical resection can be considered for patients who present with the following:
The principles of surgical resection involve obtaining a clear margin around a tumor, which may require any of the following:
Hepatic resection is controversial in patients with limited multifocal disease.
Preoperative assessment includes three-phase helical computed tomography, magnetic resonance imaging, or both to determine the presence of an extension of a tumor across interlobar planes and potential involvement of the hepatic hilus, hepatic veins, and inferior vena cava. Tumors can be resected only if a sufficient amount of liver parenchyma can be spared with adequate vascular and biliary inflow and outflow. Patients with well-compensated cirrhosis can generally tolerate resection of up to 50% of their liver parenchyma. After considering the location and number of tumors, and the patient's hepatic function, only 5% to 10% of liver cancer patients will prove to have localized disease amenable to resection. The 5-year OS rates following curative resection range between 27% and 70% and depend on tumor stage and underlying liver function.
When tumor excision, either by transplant or resection, is not feasible or advisable, ablation techniques may be used if the tumor can be accessed percutaneously or, if necessary, through minimally invasive or open surgery. Ablation can be achieved in the following ways:
Ablation may be particularly useful for patients with early HCC that is centrally located in the liver and cannot be surgically removed without excessive sacrifice of functional parenchyma.
Ablation should include a margin of normal liver around the tumor. Ablation is relatively contraindicated for lesions in close proximity to bile ducts, the diaphragm, or other intra-abdominal organs that might be injured during the ablation. Furthermore, when tumors are located adjacent to major vessels, the blood flow in the vessels may decrease the temperature reached when thermal ablation techniques such as RFA are used. This is known as the heat sink effect, which may preclude a complete tumor necrosis.
Percutaneous ethanol injection (PEI) obtains good results in patients with Child-Pugh class A cirrhosis and a single tumor less than 3 cm in diameter. In those cases, the 5-year OS rate is expected to be as high as 40% to 59%.[Level of evidence: 3iiiD]
RFA also achieves best results in patients with tumors smaller than 3 cm. In this subpopulation of patients, 5-year OS rates may be as high as 59%, and the recurrence-free survival rates may not differ significantly from treatment with hepatic resection. Local control success progressively diminishes as the tumor size increases beyond 3 cm.
In the few randomized, controlled trials that included patients with Child-Pugh A cirrhosis, RFA proved superior to PEI in terms of rates of complete response and local recurrences; some of those studies have also shown improved OS with RFA. Furthermore, RFA requires fewer treatment sessions than PEI to achieve comparable effects.
Of note, RFA may have higher complication rates than PEI, but both techniques are associated with lower complication rates than excision procedures.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with adult primary liver cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
Llovet JM, Fuster J, Bruix J: Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation. Hepatology 30 (6): 1434-40, 1999.
Hemming AW, Cattral MS, Reed AI, et al.: Liver transplantation for hepatocellular carcinoma. Ann Surg 233 (5): 652-9, 2001.
Chok KS, Ng KK, Poon RT, et al.: Impact of postoperative complications on long-term outcome of curative resection for hepatocellular carcinoma. Br J Surg 96 (1): 81-7, 2009.
Kianmanesh R, Regimbeau JM, Belghiti J: Selective approach to major hepatic resection for hepatocellular carcinoma in chronic liver disease. Surg Oncol Clin N Am 12 (1): 51-63, 2003.
Poon RT, Fan ST, Lo CM, et al.: Long-term survival and pattern of recurrence after resection of small hepatocellular carcinoma in patients with preserved liver function: implications for a strategy of salvage transplantation. Ann Surg 235 (3): 373-82, 2002.
Huang GT, Lee PH, Tsang YM, et al.: Percutaneous ethanol injection versus surgical resection for the treatment of small hepatocellular carcinoma: a prospective study. Ann Surg 242 (1): 36-42, 2005.
Yamamoto J, Okada S, Shimada K, et al.: Treatment strategy for small hepatocellular carcinoma: comparison of long-term results after percutaneous ethanol injection therapy and surgical resection. Hepatology 34 (4 Pt 1): 707-13, 2001.
Huang J, Hernandez-Alejandro R, Croome KP, et al.: Radiofrequency ablation versus surgical resection for hepatocellular carcinoma in Childs A cirrhotics-a retrospective study of 1,061 cases. J Gastrointest Surg 15 (2): 311-20, 2011.
Zhou YM, Shao WY, Zhao YF, et al.: Meta-analysis of laparoscopic versus open resection for hepatocellular carcinoma. Dig Dis Sci 56 (7): 1937-43, 2011.
Lencioni RA, Allgaier HP, Cioni D, et al.: Small hepatocellular carcinoma in cirrhosis: randomized comparison of radio-frequency thermal ablation versus percutaneous ethanol injection. Radiology 228 (1): 235-40, 2003.
Lin SM, Lin CJ, Lin CC, et al.: Randomised controlled trial comparing percutaneous radiofrequency thermal ablation, percutaneous ethanol injection, and percutaneous acetic acid injection to treat hepatocellular carcinoma of 3 cm or less. Gut 54 (8): 1151-6, 2005.
Brunello F, Veltri A, Carucci P, et al.: Radiofrequency ablation versus ethanol injection for early hepatocellular carcinoma: A randomized controlled trial. Scand J Gastroenterol 43 (6): 727-35, 2008.
Shiina S, Teratani T, Obi S, et al.: A randomized controlled trial of radiofrequency ablation with ethanol injection for small hepatocellular carcinoma. Gastroenterology 129 (1): 122-30, 2005.
TAE is the most widely used primary treatment for hepatocellular carcinoma (HCC) when HCC is not amenable to curative treatment by excision or ablation. The majority of the blood supply to the normal liver parenchyma comes from the portal vein, while blood flow to the HCC comes mainly from the hepatic artery. Furthermore, HCC tumors are generally hypervascular compared with the surrounding normal parenchyma. The obstruction of the arterial branch(es) feeding the tumor may reduce the blood flow to the tumor and result in tumor ischemia and necrosis.
Embolization agents, such as microspheres and particles, may also be administered along with concentrated doses of chemotherapeutic agents (generally doxorubicin or cisplatin) mixed with lipiodol or other emulsifying agents during chemoembolization, arterial chemoembolization, usually via percutaneous access; and TACE. TAE-TACE is considered for patients with nonsurgical HCC, who are also not amenable to percutaneous ablation in the absence of extrahepatic disease. In patients with cirrhosis, any interference with arterial blood supply may be associated with significant morbidity and is relatively contraindicated in the presence of portal hypertension, portal vein thrombosis, or clinical jaundice. In patients with liver decompensation, TAE-TACE could increase the risk of liver failure.
A number of randomized, controlled trials have compared TAE and TACE with supportive care. Those trials have been heterogeneous in terms of patient baseline demographics and treatment. The survival advantage of TAE-TACE over supportive care has been demonstrated by two trials. No standardized treatment for a TAE approach has been determined (e.g., embolizing agent, chemotherapy agent and dose, treatment schedule). However, a meta-analysis has shown that TAE-TACE improves survival more than supportive treatment.
The use of drug-eluting beads (DEB) for TACE has the potential of reducing systemic side effects of chemotherapy and may increase objective tumor response. Only one study has suggested that DEB-TACE may offer an advantage in overall survival (OS).
At this time, there is no evidence supporting a survival benefit for patients with advanced HCC receiving systemic cytotoxic chemotherapy when compared with no treatment or best supportive care.
Sorafenib is an oral multikinase inhibitor that prolongs survival in patients with advanced HCC and well-compensated liver function.
The SHARP [NCT00105443] trial randomly assigned 602 patients with advanced HCC to receive either sorafenib 400 mg twice daily or a placebo. All but 20 of the patients had a Childs-Pugh A liver disease score; 13% were women. After 321 deaths, the median survival was significantly longer in the sorafenib group (10.7 months vs. 7.9 months on placebo; hazard ratio [HR] favoring sorafenib, 0.69; 95% confidence interval [CI], 0.55–0.87; P < .001).
A subsequent, similar trial conducted in 23 centers in China, South Korea, and Taiwan included 226 patients (97% with Child-Pugh A liver function) with a 2:1 randomized assignment to sorafenib versus placebo. The median OS rate was 6.5 months for the sorafenib group versus 4.2 months for the placebo group (HR, 0.68; 95% CI, 0.50–0.93; P = .014). Adverse events attributed to sorafenib in both of these trials included hand-foot skin reactions and diarrhea.
These studies established a role for sorafenib in locally advanced and advanced hepatocellular cancers extending beyond the liver, which are not amenable to regional modalities.
Little is known about the efficacy of sorafenib for the patient with Child B or C liver function. At this time, further studies are needed before sorafenib can be recommended for a patient with Child B or C cirrhosis.
Studies are also ongoing to evaluate the role of sorafenib after TACE, with chemotherapy, or in the presence of more-advanced liver disease.
The efficacy of other targeted therapy agents (e.g., sunitinib and brivanib) is currently being investigated.
The role of radiation therapy for HCC has traditionally been limited by the low dose tolerance of the liver to radiation. However, recent technological developments in radiation therapy, including breathing motion management and image-guided radiation therapy, have allowed for more precise and targeted radiation therapy delivery to the liver. As a result of these advances, conformal liver irradiation has become feasible in the treatment of focal HCC. Several phase II studies have suggested a benefit in local control and OS compared with historical controls for patients with locally advanced HCC unsuitable for standard locoregional therapies.[Level of evidence: 3iiDiii] An ongoing, multi-institutional, randomized, phase III study (RTOG 1112 [NCT01730937]) evaluating sorafenib versus stereotactic body radiation therapy followed by sorafenib in HCC is currently open for patient accrual. This study aims to definitively evaluate the role of radiation therapy for locally advanced HCC.
Llovet JM, Real MI, Montaña X, et al.: Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet 359 (9319): 1734-9, 2002.
Lo CM, Ngan H, Tso WK, et al.: Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology 35 (5): 1164-71, 2002.
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 33 (3): 541-51, 2010.
Varela M, Real MI, Burrel M, et al.: Chemoembolization of hepatocellular carcinoma with drug eluting beads: efficacy and doxorubicin pharmacokinetics. J Hepatol 46 (3): 474-81, 2007.
Poon RT, Tso WK, Pang RW, et al.: A phase I/II trial of chemoembolization for hepatocellular carcinoma using a novel intra-arterial drug-eluting bead. Clin Gastroenterol Hepatol 5 (9): 1100-8, 2007.
Lammer J, Malagari K, Vogl T, et al.: Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study. Cardiovasc Intervent Radiol 33 (1): 41-52, 2010.
Dhanasekaran R, Kooby DA, Staley CA, et al.: Comparison of conventional transarterial chemoembolization (TACE) and chemoembolization with doxorubicin drug eluting beads (DEB) for unresectable hepatocelluar carcinoma (HCC). J Surg Oncol 101 (6): 476-80, 2010.
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 10 (1): 25-34, 2009.
Abou-Alfa GK, Schwartz L, Ricci S, et al.: Phase II study of sorafenib in patients with advanced hepatocellular carcinoma. J Clin Oncol 24 (26): 4293-300, 2006.
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 31 (13): 1631-9, 2013.
Kawashima M, Furuse J, Nishio T, et al.: Phase II study of radiotherapy employing proton beam for hepatocellular carcinoma. J Clin Oncol 23 (9): 1839-46, 2005.
This information was last updated on July 11, 2014.
Our licensed social workers are here to help adult patients and their loved ones face the many new concerns and anxieties following a cancer diagnosis, offering emotional support and assistance with obtaining needed resources.
Our support groups are geared to specific cancers and methods of treatment. They give patients the opportunity to meet and share information and moral support. Our experienced, compassionate staff facilitates and guides discussion.
If you are dealing with the death of a loved one, grief can be a lonely and isolating experience. The Bereavement Program provides support to bereaved family members and friends following the death of a patient.
Concierge Services is your one-stop place to learn about Dana-Farber programs, services and resources, as well as information on getting around Boston, finding lodging or restaurants, and activities in the area.
The Expressive Arts Therapy program, sponsored by the Leonard P. Zakim Center for Integrative Therapies, provides adult patients, family members, and caregivers with a variety of options to support well-being during cancer treatment. From live music meditation to painting technique workshops, the program offers a range of creative outlets to suit every interest.
Dana-Farber and Brigham and Women's Hospital, including parking facilities, are fully accessible to people with disabilities. There are wheelchairs at the main entrance, and security staff can provide personal assistance. We also have many educational materials available in large print and audiotape formats.
The Ethics Consultation Service is available for patients and families who may be facing difficult decisions and choices regarding care. Our goal is to bring together patients, families and health care providers to talk about ethical concerns and help everyone involved arrive at a resolution that is right for all.
This comprehensive resource offers guidance, information and resources to support the entire family, including how to talk to children about cancer, advice for the well partner, and creating a support network.
Find practical tips and suggestions for individuals caring for a family member or friend with cancer, including creating a caregiving plan, finding community resources, and looking after your own well-being.
Friends' Place provides personal consultations to help cancer patients of all ages cope with changes in physical appearance that result from cancer treatment. Our experienced, compassionate team provides fittings for compression garments or breast prostheses, helps with wigs and other head coverings, and offers make-up and skincare advice.
The Friends' Corner Gift Shop, located on the first floor of the Yawkey Center for Cancer Care, offers a wide selection of unique gifts and everyday items for patients, families and staff.
Dana-Farber offers several services to help you and your family manage the financial side of cancer treatment. From creating bill payment schedules and estate planning advice to debt management and resource assistance for patients in need, our team is here for you.
Every year, thousands of patients with cancer from around the world come to Dana-Farber for their care. We provide a wide array of logistical and other services for individuals who live outside the United States.
Dana-Farber provides interpreting services for patients whose first language is not English. Interpreters may be requested for any activity, including registration, booking appointments, attending treatments and exams, support groups, and meetings with doctors and other members of your health care team.
Our nutritionists are registered dietitians who can assist you in planning an optimal diet during any stage of your cancer journey, cope with any side effects you may experience, and answer your questions about the latest findings on cancer and nutrition.
One-to-One connects adult patients, family members and caregivers with individuals who have gone through cancer themselves, providing an experienced and reassuring perspective for those facing a cancer diagnosis, treatment and recovery.
The Eleanor and Maxwell Blum Patient and Family Resource Center and its satellite resource rooms are staffed by health care professionals and provide computer stations, books, brochures, videos, and CDs to help you find information and support on a variety of issues about cancer treatment and care.
Patients websites help friends and family members stay up-to-date on their loved ones' condition and write messages of support and encouragement.
The Dana-Farber pharmacy fills prescriptions for all pediatric and adult patients. Our pharmacists are an extension of the patient care team and work closely with your physicians to provide seamless, convenient, safe care.
More than 1,200 Dana-Farber patients and their families have enjoyed free trips to baseball games, theater shows, museums, and other attractions this year through the Recreational Resources program.
The Sexual Health Program provides education, consultation and personalized rehabilitation for patients and their partners who have experienced changes in sexual health during and after cancer treatment.
Through all stages of cancer treatment and survivorship, our Spiritual Care staff is available 24 hours a day to provide emotional and spiritual support for adults and pediatric patients and family members.
Young adults with cancer face very different challenges than patients who were diagnosed earlier in childhood or later in adulthood. The Young Adult Program can help you to find the resources and expertise available at Dana-Farber to help support your cancer experience.
Integrative therapies, also known as complementary therapies, range from acupuncture and massage to nutritional guidance and music therapy. Patients treated at the Zakim Center credit its services with easing nausea, improving circulation, and reducing pain, stress, and anxiety associated with cancer treatment.