Treatment Update: Liver Cancer

After your diagnosis, you and your health care team will discuss the best way to proceed with your treatment. Factors that influence the choice of treatment include the number of tumors in the liver, whether the cancer has affected blood vessels, how much the liver has been damaged by the cancer and whether the cancer has spread to other parts of the body (metastasized).

Surgery

A partial hepatectomy is the surgical removal of the part of the liver affected by cancer. This procedure may be an option for people whose tumor (or tumors) are confined to a small section of the liver, are not near blood vessels and whose liver is not damaged by cirrhosis.

Transplant

A liver transplant is a possible option for people whose tumors are very small, few in number, do not involve blood vessels and have not spread outside the liver. To receive a transplant, a suitable donor with a healthy liver must be found following evaluation by a transplant surgery team. In the United States, the most common type of liver transplant is “orthotopic,” meaning the diseased liver is replaced by all or part of a normal liver from a living or deceased donor.

Embolization

A minimally invasive procedure called transarterial embolization (TAE) may be considered in cases where surgery is not an option. In TAE, an interventional radiologist injects tiny particles made of gelatin sponges or beads into a catheter (small plastic tube) that has been placed into the hepatic artery, the main source of blood for most liver tumors. This kills tumors by blocking their blood supply.

If chemotherapy is injected into the catheter along with the particles, the procedure is called transarterial chemoembolization (TACE). The chemotherapy is targeted directly to the tumors, sparing healthy tissue from the effects of the drug. Chemotherapies that may be used alone or in combination in TACE include cisplatin, doxorubicin and mitomycin.

Treating primary liver cancer with TAE or TACE may allow for future surgery or transplant.

Ablation

Ablation is a treatment that uses different methods, such as heat, freezing or microwaves, to destroy cancer cells. In radiofrequency ablation (RFA) and microwave ablation (MWA) the doctor uses an imaging technique, such as an ultrasound or CT scan, to guide a needle into the tumor. High-frequency electrical currents (in RFA) or microwaves (in MWA) are passed through the needle, creating a small region of heat that destroys the tumor.

Cryoablation is a technique similar to RFA and MWA, but uses cold instead of heat to destroy tumors. Ablation may be an effective option for people for whom surgery is not an option, and whose tumors are small.

Tyrosine Kinase Inhibitors

Tyrosine kinase inhibitors (TKIs) are a class of drug that focus on specific molecules and cell mechanisms thought to be important for cancer cell survival and growth, taking advantage of what researchers have learned in recent years about how cancer cells grow.

There are four TKIs approved by the U.S. Food and Drug Administration (FDA) for the treatment of HCC:

• Lenvatinib (Lenvima) is used as a first-line (initial) treatment of unresectable (inoperable) HCC. Lenvatinib inhibits the growth of cancer cells and blood vessels by blocking certain enzymes. (Blood vessels carry oxygen, minerals and other nutrients that tumors need to grow.)

• Sorafenib (Nexavar) works by blocking the action of proteins that promote the growth of new blood vessels. Sorafenib also blocks some of the proteins on cancer cells that help them grow and multiply.

• Regorafenib (Stivarga) is approved for the treatment of people who had been previously treated with sorafenib. Like sorafenib, regorafenib is designed to block the formation of new blood vessels, as well as block proteins that contribute to the growth of cancer cells.

• Cabozantinib (Cabometyx) is approved for the treatment of people with HCC who previously received sorafenib. Cabozantinib targets multiple enzymes that are part of many cell functions, including growth and division.

Immunotherapy

Our immune system is constantly working to keep us healthy. It recognizes and fights against danger, such as infections, viruses and growing cancer cells. In general terms, immunotherapy uses our own immune system as a treatment against cancer. In recent years, immunotherapy has emerged as an important treatment option for HCC.

There are three immunotherapies for advanced HCC previously treated with the TKI sorafenib. Called immune checkpoint inhibitors, they interfere with molecular “brakes” that prevent the body’s immune system from attacking tumors. Nivolumab (Opdivo) and pembrolizumab (Keytruda) work by interfering with the PD-1 brake. The combination of nivolumab and ipilimumab (Yervoy) interferes with the PD-1 and CTLA-4 brakes.

In 2020, the FDA approved atezolizumab (Tecentriq) in combination with bevacizumab (Avastin) as an initial treatment for HCC that has spread beyond the liver or is inoperable. Atezolizumab interferes with a molecular brake called PD-L1. Bevacizumab works by blocking the action of VEGF (vascular endothelial growth factor), a protein released by tumors which promotes the formation of blood vessels. By blocking this protein, bevacizumab “starves” tumors.

In October 2022, the FDA approved tremelimumab (Imjudo) in combination with durvalumab (Imfinzi) for the treatment of unresectable (inoperable) HCC. Both tremelimumab and durvalumab are monoclonal antibodies, a type of immunotherapy. Anticancer monoclonal antibodies are made in the laboratory and then administered intravenously to target cancer cells.

Radiation

Radiation is sometimes used to shrink liver tumors or to relieve pain The types of radiation used in the treatment of liver cancer include:

• Stereotactic body radiation therapy (SBRT) is a technique that delivers the highest appropriate dose in the fewest number of treatment sessions. The radiation is precisely targeted to the tumor, sparing healthy tissue.

• Intensity-modulated radiation therapy (IMRT) is a form of external beam radiation therapy (EBRT) that directs a beam (or multiple beams) of radiation through the skin to the tumor. Unlike standard EBRT, IMRT allows a higher dose of radiation to be directed to the tumor, while minimizing the amount of radiation received by healthy tissue.

• 3-dimensional conformal radiation therapy (3D-CRT) uses a computer to create a 3-dimensional picture of the tumor, allowing for the highest appropriate dose of radiation to be directed to the tumor, while sparing healthy tissue as much as possible.

Radioembolization

Radioembolization is a procedure that combines embolization and radiation therapy to treat liver cancer. Small radioactive beads are placed inside the blood vessels that feed tumors, allowing concentrated amounts of radiation to attack the tumor. Radioembolization delivers an intense dose of radiation to the cancer cells while minimizing the effect on healthy tissue.

Chemotherapy

Liver cancer does not generally respond to systemic chemotherapy (treatment that is given orally or injected into a vein), whether used as single drug or as a combination of drugs. A few chemotherapy drugs, including doxorubicin, 5-fluorouracil and cisplatin, have had some limited effectiveness in shrinking tumors.

Because of HCC’s poor response to systemic chemotherapy, researchers are studying hepatic artery infusion (HAI), in which chemotherapy drugs are injected directly into the hepatic artery.

All cancer treatments can cause side effects. It’s important that you report any side effects you experience to your health care team so they can help you manage them. Report them right away—don’t wait for your next appointment. Doing so may improve your quality of life and allow you to maintain your treatment plan. It’s important to remember that not all people experience all side effects, and people may experience side effects not listed here.

Side Effects of Embolization

Post-embolization syndrome (PES) is a common side effect of transarterial embolization (TAE) and transarterial chemoembolization (TACE). PES can cause flu-like symptoms such as pain, fever and nausea.

Chemotherapy-related side effects may be experienced with TACE. Those side effects may include:

• Hair loss
• Increased risk of infection (from having too few white blood cells)
• Easy bruising or bleeding
• Changes in memory or thinking
• Peripheral neuropathy (numbness or tingling in hands and feet)

Side Effects of Tyrosine Kinase Inhibitors

Common side effects of TKIs include diarrhea, rash, liver problems (such as hepatitis and elevated liver enzymes), high blood pressure and problems with blood clotting and wound healing.

Specific TKIs may have unique side effects. It’s important to have a discussion with your health care team to understand what these potential side effects are, how to reduce the risk of their occurring, and how to minimize their impact should you experience them.

Side Effects of Immunotherapy

Immunotherapy helps to prompt an immune response against cancer cells. Because the immune system may attack healthy cells as well as cancer cells, certain side effects may be experienced, including fatigue, digestive tract symptoms, shortness of breath and rash. These effects can be mild, moderate or severe. In some cases, immunotherapy may be temporarily halted. Additionally, steroids may be given to stop an immune response against healthy cells. Some side effects of immunotherapy may be chronic and will require ongoing treatment.

Side Effects of Radiation Therapy

Changes to the skin is the most common side effects of radiation therapy. Those changes can include dryness, swelling, peeling, redness and blistering. Sun exposure should be avoided, as it can worsen this side effect. If a reaction occurs, contact your health care team so the appropriate treatment can be prescribed. It’s especially important to contact your health care team if there is any open skin or painful area, as this could indicate an infection. Infections can be treated with an oral antibiotic or topical antibiotic cream.

Some side effects may occur across treatment approaches. This section provides tips and guidance on how to manage these side effects should they occur.

Managing Digestive Tract Symptoms

Nausea and vomiting

• Eat small, frequent meals.

• Avoid food with strong odors, as well as overly sweet, greasy, fried or highly seasoned food.

• Having something in your stomach when you take medication may help ease nausea.

• Do not lie down within two hours after eating.

Diarrhea

• Drink plenty of water. Ask your doctor about using drinks such as Gatorade, which provide electrolytes. Electrolytes are body salts that must stay in balance for cells to work properly.

• Over-the-counter medicines such as loperamide (Imodium A-D and others) and prescription drugs are available for diarrhea but should be used only if necessary and with your health care team’s guidance. If the diarrhea is bad enough that you need medicine, contact a member of your health care team.

• Choose foods that contain soluble fiber, like whole grain products, oat cereals and flaxseed, and high-pectin foods such as peaches, apples, oranges, bananas and apricots.

• Avoid beans, as they can cause gas and worsen diarrhea.

• Avoid food high in refined sugar and those sweetened with sugar alcohols such as sorbitol and mannitol.

Loss of appetite

• Eating small meals throughout the day is an easy way to take in more protein and calories, which will help maintain your weight. Try to include protein in every meal. Nutrition shakes or protein drinks are a way to add calories to your daily diet.

• To keep from feeling full early, avoid liquids with meals or take only small sips (unless you need liquids to help swallow). Drink most of your liquids between meals.

• Keep high-calorie, high-protein snacks on hand such as hard-boiled eggs, peanut butter, cheese, ice cream, granola bars, liquid nutritional supplements, puddings, nuts, canned tuna and trail mix.

• If you are struggling to maintain your appetite or weight, talk to your health care team about a referral to a dietician or nutritionist who has specialist-level oncology knowledge. You can also ask your doctor whether appetite-building medication could be right for you.

Constipation

• As hydration is important to avoid constipation, make sure to drink plenty of fluids. Also, limit your intake of caffeine and alcoholic beverages, as they can cause dehydration.

• Include foods high in fiber in your daily diet, such as fruit (especially pears and prunes), vegetables and cereals. If your health care team approves, you may want to add synthetic fiber to your diet, such as Metamucil, Citrucel or FiberCon.

• Be as physically active as you can, after checking with your health care team on the level of physical activity that is right for you.

• If your doctor has prescribed a “bowel regimen,” make sure to follow it exactly.

Managing Fatigue

Fatigue (extreme tiredness not helped by sleep) is one of the most common side effects of cancer and many cancer treatments. If you are very fatigued while on treatment, your doctor may change the dose or schedule of the drug(s) you are taking, as long as that does not make the treatment less effective. If you are experiencing fatigue, talk to your doctor about whether a dose change is right for you.

There are a number of other tips for reducing fatigue:

• Take several short naps or breaks during the day.

• Take walks or do some light exercise, if possible.

• Try easier or shorter versions of the activities you enjoy.

• Ask your family or friends to help you with tasks you find difficult or tiring. There are also prescription medications that may help. Your health care team can provide guidance on whether medication is the right approach for your individual circumstances.

Managing Pain

There are a number of options for pain relief, including prescription and over-the-counter medications. It’s important to talk to a member of your health care team before taking any over-the-counter medication to determine if it is safe and will not interfere with your treatment. Many pain medications can lead to constipation. Your doctor can recommend over-the-counter or prescription medications that help to avoid or manage constipation.

Physical therapy, acupuncture, progressive muscle relaxation exercises and massage may also be of help in managing your pain. Consult with a member of your health care team before beginning any of these activities.

Frequently Asked Questions

Q: What are the treatments for liver cancer that has spread from another location in the body?

A: Cancer can spread to the liver after originating in another part of the body, such as the colon, stomach or breast. Treatment for these tumors depends on where the cancer originated. Surgery is a potential option for both primary liver cancer and cancer that has spread to the liver from another place in the body, depending on the number, size and location of the tumors.

Q: Should a person diagnosed with liver cancer seek a second opinion?

A: At the time of diagnosis, it makes sense to seek a consultation from a major cancer center or a group of physicians who are experts in managing primary liver cancer. Another time to seek a consultation or second opinion is if the cancer is not responding to treatment and/or if a change in treatment is warranted. Discussions can include possible changes in treatment approaches, and if participation in a clinical trial should be considered.

Q: I’ve had hepatitis C. Should I be tested for liver cancer?

A: Hepatitis C is a condition characterized by inflammation of the liver, resulting from infection with the hepatitis C virus. Over the course of many years, this inflammation can lead to cirrhosis (scarring throughout the liver), a risk factor for primary liver cancer. People with cirrhosis should get regular screenings, including diagnostic ultrasound, to check for liver tumors.

Q: What is ascites and how is it treated?

A: Ascites is the accumulation of protein-containing (ascitic) fluid in the abdomen. It may develop in people with HCC who also have liver damage. The basic treatment for ascites is a low-sodium diet along with bed rest. In some cases, diuretics (medications designed to increase the amount of water and salt expelled from the body) are prescribed; more rarely, a surgical procedure may be needed to remove the fluid.