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Liver Cancer

 

The liver is the largest organ inside of the body. It is located on the right side of the abdomen behind the ribs. The liver has many important functions, including:

 

• Removing harmful substances from the blood.

• Making bile that helps in the digestion of fats from food.

• Storing glycogen (sugar) that the body can use for energy.

When cancer is identified in the liver, it is important to know whether the cancer started in the liver (hepatocellular carcinoma) or spread to the liver from another organ such as the colon or lung. The treatment information in this section focuses on primary liver cancer. If your cancer began in another organ and has spread to the liver (metastasized), visit the treatment information for that specific cancer.

 

Benign Liver Tumors

 

When cells grow abnormally, they can form a mass known as a tumor. Tumors may be benign (not cancer) or malignant (cancer). Benign liver tumors do not spread to other parts of the body, but they may require treatment if they cause symptoms, post a risk of bleeding or rupture, or appear suspicious for cancer. When treatment is required, benign liver tumors can often be surgically removed. Some of the more common types of benign liver tumors are hemangioma, nodular hyperplasia, and adenoma.

 

Liver Cancer

 

In contrast to benign liver tumors, liver cancer has the capacity to spread to other parts of the body. There are several different types of liver cancer:

 

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults. It begins in the liver cells known as   hepatocytes.

Cholangiocarcinoma is cancer that develops in the cells that line the bile ducts within the liver.

Hepatoblastoma is a rare type of liver cancer that develops in children.

Angiosarcoma and Hemangiosarcoma are rare cancers that start in the blood vessels of the liver.

 

Each year in the United States, there are more than 42,810 individuals diagnosed with primary liver cancer and more than 30,160 deaths from the disease.  Liver cancer rates have tripled since 1980, while the death rates have more than doubled during this time.

 

Because hepatocellular carcinoma accounts for 80-90% of all primary liver cancers, the liver cancer information that follows focuses primarily on this type of cancer.

 

Signs & Symptoms of Liver Cancer

 

Liver cancer often causes no symptoms during its early stages. Symptoms that you may experience as the cancer grows however can include the following:

 

 Pain in the upper abdomen on the right side; the pain may extend to the back and shoulder

 

• Swollen abdomen (bloating)

• Weight loss

• Loss of appetite and feelings of fullness

• Weakness or feeling very tired

• Nausea and vomiting

• Yellow skin and eyes, and dark urine from jaundice

• Fever

These signs and symptoms can be caused by other conditions and do not necessarily mean that you have cancer, but it’s a good idea to discuss them with your doctor

 

Cause of Liver Cancer

 

Liver cancer begins when healthy cells acquire a genetic change (mutation) that causes them to turn into abnormal cells. Hereditary conditions, chronic viral infection of the liver and heavy alcohol use all contribute to the development of liver cancer.

 

 

Risk Factors for Development of Liver Cancer

 

Risk factors for liver cancer include:

 

• Hereditary hemochromatosis

• Chronic infection with hepatitis B virus (HBV)

• Chronic infection with hepatitis C virus (HCV)

• Heavy alcohol use

 

Diagnosis & Test for Liver Cancer

 

When liver cancer is suspected, imaging tests such as ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) play an important role in confirming the diagnosis. Blood levels of a protein known alpha-fetoprotein (AFP) will also be assessed. Elevated levels of AFP in combination with a liver mass is a common indication of liver cancer. When a liver mass is present and AFP levels are normal, additional imaging procedures may be used to help confirm or exclude the diagnosis of liver cancer.

 

In contrast to many other types of cancer, biopsy (removal of a sample of tissue) is often not required to diagnosis liver cancer.  For most patients (particularly those with cirrhosis), imaging and lab tests provide reliable information about the diagnosis. Furthermore, biopsy of liver cancer carries a small risk of spreading the cancer. Biopsy may be considered, however, in circumstances when there is doubt about the diagnosis.

 

Evaluation of Liver Cancer

 

The following tests may be used to evaluate the cancer and determine the extent of spread of the cancer.

 

• Computed Tomography (CT) Scan: A CT scan is a technique for imaging body tissues and organs, during which X-ray transmissions are converted to detailed images, using a computer to synthesize X-ray data. A CT scan is conducted with a large machine positioned outside the body that can rotate to capture detailed images of the organs and tissues inside the body. This method is more sensitive and precise than an X-ray.

• Magnetic Resonance Imaging (MRI): MRI uses a magnetic field rather than X-rays and can often distinguish more accurately between healthy and diseased tissue. MRI gives better pictures of tumors located near bone than CT, does not use radiation as CT does, and provides pictures from various angles that enable doctors to construct a three-dimensional image of the tumor.

• Ultrasound: Ultrasound is a technique that uses sound waves to differentiate tissues based on varying tissue density.

 

Genetic Mutations

 

Not all liver cancer cells are alike. They may differ from one another based on what genes have mutations. Molecular testing can be performed to identify cancer causing genetic mutations or the proteins they produce. By testing an individual’s liver cancer for specific unique biomarkers doctors can offer the most personalized treatment approach utilizing precision cancer medicines. All individuals with liver cancer should discuss the role of genomic testing for the management of their cancer with their doctor.

 

The following is a general overview of the treatment of liver (hepatocellular carcinoma), the most common type of primary liver cancer. Treatment may consist of surgery, liver directed therapy, and systemic treatment with precision cancer medicines or chemotherapy.  Choice of treatment will depend on the extent and location of the cancer, the presence of treatment directing biomarkers identified with genomic testing, the health of the liver, and the overall health of the patient.

 

Surgical Treatment of Hepatocellular Carcinoma

 

For patients who are healthy enough to undergo surgery and who have early-stage cancer confined to the liver, treatment typically consists of surgical resection of the cancer or liver transplantation.

 

Resection: Resection refers to surgical removal of the cancer and some surrounding normal tissue. This is often the treatment of choice in patients without cirrhosis.  Although resection is potentially curative, an estimated 70% of patients will develop a cancer recurrence during the first five years after treatment. Furthermore, resection is only possible when the remaining part of the liver is healthy enough to function on its own after surgery. For many patients with cirrhosis or other liver disease, this will not be the case and other treatment options will need to be considered.

 

Liver transplantation: For selected patients who have cancer that is confined to the liver but cannot be surgically resected, liver transplantation may be an option. A benefit of liver transplantation is that it treats not only the cancer but also any underlying liver disease such as cirrhosis. Because the number of donor livers is limited, however, liver transplantation is generally reserved for those patients who are expected to have the best survival and the lowest risk of recurrence after transplantation. According to the commonly used “Milan criteria,” for example, transplant candidates should have a single liver nodule that measures no more than 5 cm or two or three nodules that measure no more than 3 cm each. These criteria are fairly restrictive, and the question of whether and how to expand the criteria to include more patients is currently being evaluated.

 

Possibililties to improve Treatment

 

The major research focus in liver cancer is the identification of additional cancer driving mutations as targets for precision cancer medicines and the development of immunotherapy treatment strategies to be used alone or in combination with precision cancer medicines.

 

Systemic Therapies: Precision Cancer Medicine and Chemotherapy

 

Systemic therapy is any treatment directed at destroying cancer cells throughout the body, and may include chemotherapy, precision cancer medicines, or immunotherapy. Most patients with advanced cancers will be treated with systemic therapy to attack cancer cells throughout the body. The goal of administering systemic therapy is to reduce the risk of cancer recurrence, relieve symptoms, delay cancer progression and prolong survival.  Systemic therapy is typically delivered by a medical oncologist and may include one or a combination of medications.

 

Precision Cancer Medicines  In recent years the greatest progress in the management of liver cancer treatment is the development of effective precision cancer medicines and immunotherapy.  Precision cancer medicine utilizes molecular diagnostic testing, including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome. Once a genetic abnormality is identified, a specific targeted therapy can be designed to attack a specific mutation or other cancer-related change in the DNA programming of the cancer cells. Precision cancer medicine uses targeted drugs and immunotherapies engineered to directly attack the cancer cells with specific abnormalities, leaving normal cells largely unharmed.

 

Nexavar® (sorafenib): The targeted therapy Nexavar was the first systemic therapy demonstrated to improve survival in hepatocellular carcinoma (HCC) and is a standard treatment option. Nexavar inhibits biological pathways involved in cell proliferation and the development of new blood vessels. Newer precision cancer medicines produce better outcomes than Nexavar which is now typically used as a second, or third line treatment. The most common side effects of Nexavar are diarrhea, weight loss, and hand-foot skin reaction.

 

Lenvima (lenvatinib) is an oral anti-angiogenic therapy that targets new blood vessel growth and “starves” cancer of the nutrients it needs to grow. The REFLECT clinical trial enrolled 954 treatment-naive patients with metastatic or unresectable HCC to receive treatment with either Lenvima or Nexavar.  Overall 41% of Lenvima treated patients responded to treatment compared to 12% for Nexavar. The average time to cancer progression nearly doubled to 7.3 months for Lenvima compared to 3.6 months for Nexavar.

 

Cabometyx (cabozantinib) is an oral inhibitor of multiple receptor tyrosine kinases, including RET, MET, and vascular endothelial growth factor 2 (VEGFR2), which are all involved in both normal cellular function and pathologic processes, such as oncogenesis, metastasis, tumor angiogenesis, and maintenance of the tumor microenvironment.  In a clinical trial involving 707 patients with HCC who had experienced disease progression with Nexavar, or other systemic therapies Cabometyx treated patients survived longer and had a 56% reduction in the risk for progression or compared to no further treatment.

 

Stivarga (regorafenib): The FDA approved the multi-kinase inhibitor Stivarga in April 2017 for patients with HCC who have been previously treated with Nexavar Patients with advanced HCC who were treated with second-line Stivarga experienced prolonged overall survival according to a 2-year updated analysis of key findings from the pivotal RESORCE clinical trial which compared Stivarga to no further treatment in patients with HCC.

 

Cyramza (ramucirumab) is a type of targeted agent known as a monoclonal antibody. It belongs to a class of drugs known as angiogenesis inhibitors that work by blocking the growth of new blood vessels to the cancer to starve it of nutrients. Cyramza was demonstrated to improves survival in a subset of patients with hepatocellular carcinoma who have high levels of the plasma protein α-fetoprotein (AFP), which is associated with a poor prognosis leading to U.S. Food and Drug Administration (FDA) approval in May 2019.

 

Checkpoint Inhibitor Immunotherapy  Checkpoint inhibitors are a novel precision cancer immunotherapy that helps to restore the body’s immune system in fighting liver cancer by releasing checkpoints that cancer uses to shut down the immune system. PD-1 and PD -L1 are proteins that inhibit certain immune responses, allowing cancer cells to evade an attack by the body’s immune cells. Checkpoint inhibitor drugs that block the PD-1 pathway enhance the ability of the immune system to fight cancer. By blocking the binding of the PD-L1 ligand these drugs restore an immune cells’ ability to recognize and fight the liver cancer cells. A diagnostic test to measure the level of PD-L1 is available.

 

• Keytruda® (pembrolizumab)

• Imfinzi (durvalumab)

• Tecentriq® (atezolizumab)

 

Some patients with HCC respond to treatment with checkpoint inhibitors and patients should discuss the role of this immunotherapy with their doctor.

 

Chemotherapy  Chemotherapy uses medications that can be taken orally as a pill or are injected into a vein to kill cancer cells. In some situations, chemotherapy is combined with immunotherapy or other precision cancer medicines to achieve the best results.

 

Clinical Trials:

 

New anti-cancer therapies continue to be developed and evaluated in clinical trials. There are three phases of clinical trials before approval.  See our clinical trials section for more information.

 

Managing Liver Metastases

 

When cervical cancer spreads to the liver, it doesn’t always cause symptoms. It may be picked up by liver function tests, which are blood tests that measure certain levels of enzymes and proteins in the blood. Abnormal levels can indicate liver disease or damage.

 

If liver metastasis causes symptoms, they can include:

 

• pain or discomfort in the mid-section

• fatigue and weakness

• weight loss/poor appetite

• fever

• bloating

• swelling in the legs

• a yellow tint to the skin or the whites of the eyes

 

In addition to liver function tests, doctors use imaging tests to diagnose liver metastases. These may include MRI (magnetic resonance imaging), CT scan (computed tomography), ultrasound, and/or PET scan (positron emission tomography). Sometimes, a combined PET/CT scan is used.

 

Your doctor also may recommend getting a sample of the suspicious area(s) for examination under a microscope (biopsy). He or she may involve an interventional radiologist to obtain precise and minimally invasive imaging.

 

The most common treatments for metastatic cervical cancer in any location (bone, brain, lung, or liver) are systemic medications, which treat cancer throughout the entire body. Systemic medications include chemotherapy, targeted therapies, and clinical trials that have already been discussed.  Liver directed therapies, including surgery, may be an option.

 

Liver Directed Therapies: There are numerous liver directed therapies available for those who are faced with a Stage 4 cervical cancer diagnosis with liver metastases or cervical cancer that has spread to the liver.  These therapies are dependent on the size, number, and location of the liver tumors. These liver directed therapies may include chemoembolization, cryoablation, cyberknife, hepatic arterial infusion, liver resection, proton beam therapy, radioembolization or SIRT, radiofrequency ablation, or SBRT.  You can learn more on our treatment page under liver directed therapies.

 

 

 

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