After patients are diagnosed with fibrolamellar carcinoma (FLC), they and their medical teams will begin exploring different treatment options. (Our Find A Doctor application can be a valuable resource for newly diagnosed patients who have not yet found a medical team.)
Surgery to remove the tumor is the only treatment that has been statistically proven to extend life. When the tumor cannot be removed completely, systemic therapies, such as chemotherapy, targeted therapy and immunotherapy, as well as other local therapies, including radiation therapy and interventional radiology techniques are often used as treatments. Systemic treatments refers to drugs or therapies that can affect the entire body, reaching tumors or cancer cells wherever they are located. Local treatments address the cancer in a specific location.
Beyond surgery, there is currently no clinically-proven “standard of care” for the disease, so non-surgical therapies can vary considerably from patient-to-patient and institution-to-institution. Because FLC is so rare, it has been difficult for investigators to complete the clinical studies that are necessary to document the benefit of different systemic treatments. Nevertheless, due to rapid developments in targeted therapy and immunotherapy, and increased FLC research efforts, treatment options for FLC patients have been expanding. The search for new curative therapies is actively underway.
There are many approaches currently being used to treat fibrolamellar carcinoma. Each person’s treatment plan is unique, depending on the size, number and location of tumors; the general condition of their health; their age; plus whether the goals for the treatment are to cure the disease, extend life or alleviate symptoms. It’s important that patients have confidence in the treatment plans their doctors suggest, so patients should feel free to get a second – even a third – opinion before proceeding with treatment.
Treatment options for FLC include:
A common treatment for fibrolamellar carcinoma (FLC) is surgical removal (resection) of the tumor. Doctors sometimes use the term resectable to describe cancers they believe can be removed by surgery and unresectable to describe those they think are too difficult to be entirely removed by surgery. Surgical treatments for FLC include both curative surgery and palliative surgery. Curative surgery removes all visible traces of cancer from the body. Palliative surgery means the goal is to “debulk” the tumor, improve symptoms, lessen pain or provide better quality of life, even when all visible tumor can’t be removed.
Surgery is the only treatment for FLC that is proven to be potentially curative. As a result, many patients will go to great lengths to make sure surgery is a viable option for their treatment, including:
- consulting with multiple surgeons about whether or not their disease can be completely resected
- working with their surgical and oncology teams to identify systemic treatments or interventional radiology treatments that could potentially shrink the disease enough to make them a candidate for surgery.
Because the liver is the only organ which can regenerate itself, it can grow to compensate for the removed portions after surgery. This can allow surgeons to resect up to 70-80% of the liver in exceptional cases. After liver surgery, liver function typically returns to normal within 2 to 3 weeks of resection surgery and liver size returns to normal within 3 to 6 months.
Surgical approaches for FLC
Two main types of surgery are used to treat FLC that has not spread beyond the liver. These include:
It is possible for tumors to recur (return) even when resection and/or transplantation has been considered successful. Different studies have shown that between 43 percent and 65 percent of all patients with liver tumors (including, but not exclusive to those with fibrolamellar) have recurrences within two years of a liver resection.
For that reason, patients are typically monitored with regular checkups and CT and/or MRI scans at regular intervals to watch for signs of recurrence. Most recurring tumors tend to appear within a few years of surgery, but patients are typically monitored for 10 years or more to be on the safe side. Depending on where they show up, recurring tumors are frequently treated with another surgery.
Chemotherapy – the use of powerful drugs to kill dividing cancer cells and prevent them from growing – is commonly used in treating fibrolamellar. Because it is a systemic treatment, chemotherapy can reach cells almost anywhere in the body. Most chemotherapies are cytotoxic chemicals, meaning that they kill cells. Chemotherapy is used as a treatment because rapidly growing and dividing cancer cells are generally more susceptible to damage by the chemo agents than normal cells.
Chemotherapy is used in three ways:
- to kill or shrink tumors when surgery is not possible, sometimes in the hope of enabling surgery after sufficient tumor shrinkage
- to kill cancer cells that have spread beyond the liver, or
- as an adjuvant therapy in combination with surgery and/or radiation
- to enhance the response of a tumor to radiation therapy
- to destroy residual cancer cells that could be left behind after surgery.
Chemotherapies used in liver cancer and FLC
There are many chemotherapy drugs that doctors can choose from. Oncologists generally choose which drug to use based on a standard protocol for a disease (the drugs with the history of the best outcomes), the stage of the cancer, as well as the health and age of the patient. Because of the rarity of cases of FLC and the lack of systematic studies to establish a clear “standard of care”, many oncologists prescribe chemotherapies for FLC based on treatments that have been shown to be effective in HCC, plus their best judgement. In light of the limited evidence supporting the use of any particular treatment in FLC, a wide variety of treatments are currently prescribed.
Because FLC tumors can be resistant to many chemotherapy drugs, oncologists often use a combination of 2 or 3 of these drugs to achieve the best results. (See rationale for combination therapies in the targeted therapy section.) The response rate to chemotherapy drugs with FLC is roughly 25 percent.1
Chemotherapies that are used to treat fibrolamellar patients include:
- 5-fluorouracil (5-FU)
- Capecitabine (Xeloda) – Capecitabine is closely related to 5-FU. Instead of being an infused drug, capecitabine comes in a pill form. It is metabolized by the body into 5-FU.
- 5-FU plus interferon
- FOLFOX (5-FU, oxaliplatin and leucovorin)
- Gemcitabine (Gemzar)
- GEMOX (gemcitabine plus oxaliplatin)
- Oxaliplatin (Eloxatin)
- Doxorubicin (pegylated liposomal doxorubicin)
- Mitoxantrone (Novantrone).
Chemotherapy is often administered by injection or infusion, though some can be administered in pill or capsule form, which can be taken at home. Since many chemotherapies are strong medications, they can potentially cause damage if repeatedly injected into a peripheral vein in a patient’s arm. Consequently, doctors will often insert a port, a nickel-sized device with an attached catheter (tube) that ends close to the heart. This position allows infused agents to be spread throughout the body quickly and efficiently, and the port allows medication to be injected into it rather than through frequent needle stick injections. The port is usually implanted under the skin in a patient’s upper chest, and can remain in place as long as necessary. Insertion of the port is done in an operating room using local anesthesia while the patient is sedated, but awake.
Doctors give chemotherapy in cycles, with each period of treatment followed by a rest period to give the body time to recover. The treatment schedule varies with the patient and the drugs used.
Other methods of administering chemotherapy that are sometimes used in FLC include:
- Transarterial chemoembolization (TACE) – with TACE, a catheter is inserted in the groin and guided into the artery that supplies the cancerous tumor. Chemotherapy drugs are delivered straight to that artery, with the goal of disrupting the tumor’s blood supply while trapping the chemotherapy inside the tumor. (See the interventional radiology section for more information)
- Percutaneous hepatic perfusion (PHP) – In PHP, the liver’s blood supply is temporarily disconnected from the body’s circulation and chemotherapy drugs are circulated through the liver for a short time. Unlike traditional chemotherapy, in which medications circulate throughout the entire body, PHP targets the liver only. As a result, oncologists can treat tumors with higher doses of chemotherapy using PHP than are possible when the chemo is given systemically.
Both TACE and PHP are minimally invasive surgeries that can be used in conjunction with other treatments, such as surgery, radiation or ablation.
Everyone reacts to chemotherapy drugs differently, but many side effects are common. Most chemotherapy drugs work by attacking cells in your body that are dividing quickly. Cancer cells form new cells more rapidly than normal cells. However, other cells in your body also divide quickly, like those in the bone marrow, the lining of the mouth and intestines, and hair follicles. As a result, these cells can also be affected by the chemotherapy drugs, which can lead to side effects. While the exact side effects of chemotherapy depend on the specific drug, dosage and length of time they are taken, typical side effects include:
- hair loss
- extreme fatigue (due to low red blood cell counts)
- increased risk of infection (due to low white blood cell counts)
- neuropathy (tingling, burning or numbness, most often in the fingers and feet).
While all of these side effects are unpleasant, not all are serious. Talking to the treatment team about them is important, as adjustments can sometimes be made when a side effect is particularly debilitating.
Targeted therapy is a newer type of cancer treatment that uses drugs or other substances to more precisely identify and attack certain types of cancer cells. Targeted drugs block the growth and spread of cancer by interfering with specific biochemical pathways in tumor cells that are important to their growth or survival. By targeting specific molecules involved in those pathways, the drugs can inhibit the growth of the tumor while limiting damage to normal cells. Targeted therapy is sometimes called “molecular targeted therapy” or “precision medicine”.
Targeted therapies differ from traditional chemotherapy in that targeted therapies try to alter how the cancer cells work. To do that, they focus on part of the cancer cell that makes it different from a healthy cell. In contrast, most standard chemotherapies kill rapidly dividing cancerous and normal cells. Like chemotherapy, targeted therapy drugs enter the bloodstream and reach most areas of the body, which makes them potentially useful against cancers that have spread. Because standard chemo is not very effective in most patients with liver cancer, doctors are focusing more on using targeted therapies.
Types of targeted therapy
There are many different types of targeted cancer drugs. They include both
- small molecule drugs that are are small enough to enter a cancer cell and target a specific substance inside the cell, and
- large molecule drugs that can’t fit inside a cell, but work by weakening or destroying proteins or enzymes on the cancer cell’s surface.
Most of these targeted therapy drugs work by one of the following mechanisms:
- Slowing or stopping the development of new blood vessels that feed the cancer cell (This type of drug is called an angiogenesis inhibitor)
- Blocking signals that tell a cancer cell to grow or divide
- Triggering the immune system to attack the cancer cell
- Changing specific proteins within a cancer cell, so the cell dies
- Carrying other types of treatments (like chemotherapy) directly to a cancer cell to kill it, while leaving normal cells alone (These are often called antibody-drug conjugates or ADCs).
Targeted therapies used in liver cancer and FLC
FLC patients are often treated with the following targeted therapies. All are approved treatments for HCC:
Rationale for combination therapies
As with any systemic therapy, cancer cells can become resistant to targeted therapy drugs, causing the drugs to become ineffective over time. This resistance can occur if the tumor cells mutate so the drug no longer interacts well with the cell targets, or if the tumor finds a new pathway to grow that does not depend on the drug’s target. To help avoid this problem, targeted therapies are frequently delivered in combination with other drugs, rather than alone.
For many cancers like fibrolamellar, it is believed that combinations of drugs – a “one-two punch” of treatment – can achieve many benefits. Potential benefits include:
- Reducing tumor resistance to the treatment. By using drug combinations, the risk that a tumor is resistant to the drug decreases.
- Attacking multiple targets at once. The use of drug combinations allows doctors to target several factors driving a cancer’s growth simultaneously. Theoretically, working on multiple molecular targets at the same time should raise the chances of killing cancer cells and eliminating a tumor.
- Taking advantage of drug synergies. Sometimes a combination of drugs can be synergistic, meaning the impact of the combination is bigger than sum of the individual effects of each drug. For example, one drug could sensitize a tumor cell to another drug, making the combination much more effective than either drug alone.
However, combination therapies also have some risks or disadvantages, including:
- Increased side effects could be experienced because more than one drug is used
- The drugs could potentially interact in ways that cause additional new side effects.
Because patients with fibrolamellar carcinoma tend to be young and (aside from the cancer) usually have no underlying liver disease, many believe the benefits of drug combinations outweigh their risks. Consequently, there is a lot of activity, from early research to clinical trials, focused on investigating the use of different combination therapies in liver cancer and FLC.
Role of genomic profiling tests
Genomic profiling provides information about the specific genetic makeup of an individual patient’s cancer cells. To get this information, a sample of tumor tissue from a recent surgery or biopsy is analyzed to identify changes in the DNA (and sometimes the RNA) of the cancer cells. These tests generally do not perform a complete genomic analysis of the patient’s tissue. Instead they often look for specific mutations for which a drug treatment is already available, or under development.
For some patients, an “actionable target” is found. This means that the test discovered a particular mutation in a patient’s tumor that can be attacked by an existing drug.
Unlike many other cancers, FLC tumors tend to have few genetic mutations other than the DNAJB1–PRKACA fusion gene. As a result, many FLC patients do not receive actionable results from these tests. Nevertheless, many FLC patients opt to pursue the testing, hoping to find and potentially benefit from new emerging targeted cancer treatments.
Many major medical centers offer this type of testing to their patients. In addition, many commercial laboratories (including Caris, Foundation Medicine, Guardant, Molecular Health, and Paradigm) also offer tumor profiling tests. If interested, patients should speak with their medical teams about the costs and potential benefits of genomic or molecular testing.
While chemotherapy works directly on tumors to kill cancer cells, immunotherapy works by “revving up” a patient’s own immune system to attack the cancer. It is another relatively new treatment that strives to improve the immune system’s ability to identify and destroy cancer cells. Immunotherapy has been used in many different types of cancer, including liver cancer.
There are several different types of immunotherapies that are being developed for many different diseases. These include:
- Checkpoint inhibitors – drugs that block proteins that stop the immune system from recognizing and attacking the cancer cells
- Adoptive cell transfer therapy – a treatment that engineers a patient’s own immune cells to better recognize the cancer, grows them in a lab, and reinserts them in the body to attack the cancer. One type of adoptive cell therapy that has already made strong progress in certain types of blood cancers is CAR-T (chimeric antigen receptor T cell) therapy.
- Monoclonal antibodies (MABs) – immune system proteins created in the lab that are designed to bind to specific targets on cancer cells. While some MABs are considered “targeted therapy”, some can be used to mark cancer cells so that they will be better seen and destroyed by the immune system.
- Treatment vaccines – vaccines which cause a person’s immune system to attack cancer cells.
- Immune system modulators – naturally occurring proteins that enhance the body’s immune response against cancer.
Immunotherapies used as treatment for FLC
Of those five types of immunotherapy, three are currently being used to treat FLC, including checkpoint inhibitors, monoclonal antibodies and immune system modulators. In each of these immunotherapy categories, patient treatment with at least one drug is already underway.
Combination therapies including immunotherapy
Across many cancers, there has been a lot of research conducted investigating the benefit of combining immunotherapy treatments (especially checkpoint inhibitors) with other therapies, including chemotherapy, targeted therapy and radiation therapy. It is thought that the breakdown of tumor cells by other drugs and localized treatments could help immune cells recognize a cancer as foreign, and therefore improve the effectiveness of the immunotherapy. Alternatively, the additional treatments could potentially drive additional immune cells to penetrate the tumor and therefore enhance the impact of the immunotherapy treatment.
Notable immunotherapy combination treatments under investigation for FLC include:
- Nivolumab, plus 5-fluorouracil (5-FU) and interferon alpha-2b. Many fibrolamellar patients have already been prescribed this “triple therapy” at some institutions. See the clinical trials page for more information about a clinical trial that is trying to understand the interactions of this combination and the value of sequencing the drugs.
- Ipilimumab plus nivolumab (approved in 2020 for the treatment of HCC).
- Atezolizumab plus bevacizumab (approved in 2020 for the treatment of HCC).
- Nivolumab plus lenvatinib.
Interventional radiology (IR) can be used to locally treat FLC tumors without major surgery.
Interventional radiologists can reach virtually every organ in the body by inserting small needles, wires or catheters through tiny incisions in the skin. IR doctors use medical imaging techniques, such as ultrasound, CT and MRI, to guide their instruments to the precise location of a tumor. As a result, doctors can complete a procedure or give treatment right where a patient needs it. Some of the benefits of interventional radiology include a reduction in the cost, recovery time, pain, and risk to patients who would otherwise need traditional open surgery.
IR techniques used in FLC
Interventional radiologists use a variety of techniques to treat cancers like FLC. These include:
Radiation is the use of high-energy electromagnetic rays to disrupt the DNA that causes cancer. Radiation can kill the cancer cells and/or stop new cells from being created. A radiation oncologist plans and directs radiation treatment in cancer patients, working with a team that may include a radiation oncology nurse, technicians, and therapists.
In some cases, radiation is used in combination with other treatments, such as surgery and/or chemotherapy. For example, radiation may be used to shrink tumors before surgery, or may be used in conjunction with chemotherapy to treat recurring tumors. Radiation can also be used to shrink tumors, make the patient more comfortable, and prolong life when surgery is not possible. Radiation is also sometimes used to treat fibrolamellar metastases outside of the liver1.
Use of radiation therapy in FLC
For cancers like FLC, radiation therapy is typically given in two ways:
For more information about radiation therapy, please visit:
Any treatment that is done to relieve the symptoms of cancer or the negative effects of cancer treatment is considered palliative care. Palliative care is not curative; rather, the idea is to make patients more comfortable and improve their quality of life while undergoing treatments. Studies have shown that palliative care can greatly enhance a patient’s quality of life during this very difficult time, especially if begun early in treatment. 1
Palliative care is usually provided by a specially-trained team of doctors, nurses and other specialists who work together with a patient’s doctors to provide an extra layer of support. Sometimes called “supportive care”, palliative care is driven by the unique needs of the individual patient, not on the patient’s prognosis. Palliative care is appropriate at any stage of a serious illness, and it can be provided along with the patient’s regular treatments.
While pain management is certainly a large part of palliative care, it’s not the only concern. Besides their physical needs, cancer patients have emotional and often spiritual needs as well. All major cancer centers have palliative care teams, including a therapist and spiritual advisor, to address those needs. There’s often also a dietitian to address nausea, weight loss, and loss of appetite, and a financial advisor to help the patient and family through the maze of bills and insurance claims.
Differences between palliative care and hospice care
It is important to make the distinction between palliative care and hospice care. The two are often confused because they overlap. However, while palliative care can and should be practiced during all stages of cancer treatment, hospice care is focused on making the patient feel cared for and comfortable in what is thought to be the last six months of life. (Therefore, hospice care includes palliative care, but palliative care is not necessarily hospice care.)
Find out more
To find out more about palliative care, talk to your oncologist or someone on your oncology care team. They can refer you to the appropriate specialists.
Click here to learn more about hospice care.
Please note: The Fibrolamellar Cancer Foundation does not provide medical advice or recommend any specific organizations or services. We provide website users with information to help them better understand their health conditions and current approaches to the diagnosis and treatment of FLC. Always seek the advice of your physician or other qualified healthcare provider.