Hepatoblastoma is a cancer that forms in the tissues of the liver. It is the most common type of childhood liver cancer and usually affects children younger than 3 years of age.

The liver is one of the largest organs in the body. It has two 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 following:

• to make bile to help digest fats from food
• to store glycogen (sugar), which the body uses for energy
• to filter harmful substances from the blood so they can be passed from the body in stools and urine

In hepatoblastoma, the histology (how the cancer cells look under a microscope) affects the way the cancer is treated. The histology for hepatoblastoma may be one of the following:

• well-differentiated fetal (pure fetal) histology
• small cell undifferentiated histology hepatoblastoma and rhabdoid tumors of the liver
• mixed epithelial and fetal histology (non–well-differentiated fetal histology, non-small cell undifferentiated histology)

Hepatoblastoma is caused by certain changes in the way the liver cells function, especially how they grow and divide into new cells. Often, the exact cause of the cell changes is unknown.

A risk factor is anything that increases the chance of getting a disease. Not every child with one or more of these risk factors will develop hepatoblastoma, and it will develop in some children who don’t have a known risk factor. Talk with your child’s doctor if you think your child may be at risk.

The following syndromes or conditions are risk factors for hepatoblastoma:

• Aicardi syndrome
• Beckwith-Wiedemann syndrome
• hemihyperplasia
• familial adenomatous polyposis (FAP)
• glycogen storage disease
• premature birth with a very low weight at birth
• Simpson-Golabi-Behmel syndrome
• certain genetic changes, such as trisomy 18

Children at risk of developing hepatoblastoma may have tests done to check for cancer before any symptoms appear. Every 3 months from birth (or diagnosis of a risk factor) until the child is 4 years old, an abdominal ultrasound exam and test to check the level of alpha-fetoprotein (AFP) in the blood are done.

Children may not have symptoms of hepatoblastoma until the tumor has grown bigger. It's important to check with your child's doctor if your child has any symptoms below:

• a lump in the abdomen
• swelling in the abdomen
• pain in the abdomen
• weight loss for no known reason
• loss of appetite
• nausea and vomiting

These symptoms may be caused by conditions other than hepatoblastoma. The only way to know is to see your child's doctor.

Tests to diagnose hepatoblastoma

If your child has symptoms that suggest hepatoblastoma, the doctor will need to find out if these are due to cancer or to another condition. The doctor will ask you when the symptoms started and how often your child has been having them. They will also ask about your child's personal and family medical history and do a physical exam. Based on these results, the doctor may recommend diagnostic tests to find out if your child has hepatoblastoma. The results of these tests will also help you and your child's doctor plan treatment.

The following tests and procedures may be used to diagnose hepatoblastoma:

Serum tumor marker test

Serum tumor marker tests measure the amounts of certain substances released into the blood by organs, tissues, or tumor cells in the body. Certain substances are linked to specific types of cancer when found in increased levels in the blood. These are called tumor markers. The blood of children who have liver cancer may have increased amounts of a hormone called beta-human chorionic gonadotropin (beta-hCG) or a protein called AFP. Other cancers, benign liver tumors, and certain noncancer conditions, including cirrhosis and hepatitis, can also increase AFP levels.

SMARCB1 gene testing

SMARCB1 gene testing is a laboratory test in which a sample of blood or tissue is tested for certain changes in the SMARCB1 gene.

Complete blood count (CBC)

A sample of blood is drawn and checked for the following:

• the number of red blood cells, white blood cells, and platelets
• the amount of hemoglobin (the protein that carries oxygen) in the red blood cells
• the portion of the blood sample made up of red blood cells

Liver function tests

Liver function tests measure the amounts of certain substances released into the blood by the liver. A higher-than-normal amount of a substance can be a sign of liver damage or cancer.

Blood chemistry studies

Blood chemistry studies measure the amounts of certain substances, such as bilirubin or lactate dehydrogenase (LDH), released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease.

Magnetic resonance imaging (MRI) with gadolinium

MRI uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the liver. A substance called gadolinium is injected into a vein. The gadolinium collects around the cancer cells so they show up brighter in the picture. This procedure is also called nuclear MRI.

CT scan (CAT scan)

A CT scan uses a computer linked to an x-ray machine to make a series of detailed pictures of areas inside the body, taken from different angles. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.

In childhood liver cancer, a CT scan of the chest and abdomen is usually done.

Ultrasound exam

An ultrasound exam is a procedure in which high-energy sound waves (ultrasound) are bounced off internal tissues or organs and make echoes. The echoes form a picture of body tissues called a sonogram. In childhood liver cancer, an ultrasound exam of the abdomen to check the large blood vessels is usually done.

Chest x-ray

A chest x-ray is an x-ray of the lungs. An x-ray is a type of high-energy radiation that can go through the body onto film, making a picture of areas inside the body.

Biopsy

Biopsy is a procedure in which a sample of tissue is removed from the tumor so that a pathologist can view it under a microscope to check for signs of cancer. The doctor may remove as much tumor as safely possible during the same biopsy procedure.

Immunohistochemistry

Immunohistochemistry uses antibodies to check for certain antigens (markers) in a sample of a patient’s tissue. The antibodies are usually linked to an enzyme or a fluorescent dye. After the antibodies bind to a specific antigen in the tissue sample, the enzyme or dye is activated, and the antigen can then be seen under a microscope. This type of test is used to check for a certain gene mutation, to help diagnose cancer, and to help tell one type of cancer from another type of cancer. This test may be used to look for changes in the INI1 gene.

Getting a second opinion

You may want to get a second opinion to confirm your child’s diagnosis and treatment plan. If you seek a second opinion, you will need to get important medical test results and reports from the first doctor to share with the second doctor. The second doctor will review the pathology report, slides, and scans before giving a recommendation. They may agree with the first doctor, suggest changes or another approach, or provide more information about your child’s cancer.

Cancer stage describes the extent of cancer in the body, especially whether the cancer has spread from where it first formed to other parts of the body.

Stages of hepatoblastoma

In hepatoblastoma, the PRETEXT and POSTTEXT groups are used instead of stage to plan treatment. The results of the tests and procedures done to detect, diagnose, and find out whether the cancer has spread are used to determine the PRETEXT and POSTTEXT groups.

Two grouping systems are used for hepatoblastoma to decide whether the tumor can be removed by surgery:

• The PRETEXT group describes the tumor before the patient has any treatment.
• The POSTTEXT group describes the tumor after the patient has had treatment such as neoadjuvant chemotherapy.

The liver is divided into four sections for the two grouping systems. The PRETEXT and POSTTEXT groups depend on which sections of the liver have cancer. There are four PRETEXT and POSTTEXT groups.

PRETEXT and POSTTEXT group I

In group I, the cancer is found in one section of the liver. Three sections of the liver that are next to each other do not have cancer in them.

PRETEXT and POSTTEXT group II

In group II, cancer is found in one or two sections of the liver. Two sections of the liver that are next to each other do not have cancer in them.

PRETEXT and POSTTEXT group III

In group III, one of the following is true:

• Cancer is found in three sections of the liver, and one section does not have cancer.
• Cancer is found in two sections of the liver, and two sections that are not next to each other do not have cancer in them.

PRETEXT and POSTTEXT group IV

In group IV, cancer is found in all four sections of the liver.

Progressive and recurrent hepatoblastoma

Hepatoblastoma can be a progressive or refractory disease. Progressive hepatoblastoma is cancer that continues to grow, spread, or worsen. Refractory hepatoblastoma is cancer that no longer responds to treatment.

Recurrent hepatoblastoma is cancer that has recurred (come back) after it has been treated. The cancer may come back in the liver or as metastatic tumors in other parts of the body. Tests will be done to help determine where the cancer has returned in the body, if it has spread, and how far. The type of treatment that your child will have for recurrent hepatoblastoma will depend on how far it has spread.

Types of treatment for hepatoblastoma

There are different types of treatment for children and adolescents with hepatoblastoma. You and your child's care team will work together to decide treatment. Many factors will be considered, such as your child's overall health and whether the cancer is newly diagnosed or has come back.

A pediatric oncologist, a doctor who specializes in treating children with cancer, will oversee treatment. The pediatric oncologist works with other healthcare providers who are experts in treating children with hepatoblastoma and who specialize in certain areas of medicine. It is especially important to have a pediatric surgeon with experience in liver surgery who can send patients to a liver transplant program if needed. This may include the following specialists and others:

• pediatrician
• radiation oncologist
• pathologist
• pediatric nurse specialist
• rehabilitation specialist
• psychologist
• social worker
• nutritionist
• child-life specialist
• fertility specialist

Your child's treatment plan will include information about the cancer, the goals of treatment, treatment options, and the possible side effects. It will be helpful to talk with your child's care team before treatment begins about what to expect.

Surgery

When possible, the cancer is removed by surgery. The types of surgery that may be done are:

• Partial hepatectomy removes the part of the liver where cancer is found by surgery. The part removed may be a wedge of tissue, an entire lobe, or a larger part of the liver, along with a small amount of normal tissue around it.
• Total hepatectomy and liver transplant is the removal of the entire liver by surgery, followed by a transplant of a healthy liver from a donor. A liver transplant may be possible when cancer has not spread beyond the liver, and a donated liver can be found. If the patient has to wait for a donated liver, other treatment is given as needed.
• Resection of metastases is surgery to remove cancer that has spread outside of the liver, such as to nearby tissues, the lungs, or the brain.

The type of surgery that can be done depends on the following:

• the PRETEXT group and POSTTEXT group
• the size of the primary tumor
• whether there is more than one tumor in the liver
• whether the cancer has spread to nearby large blood vessels
• the level of AFP in the blood
• whether the tumor can be shrunk by chemotherapy, so that it can be removed by surgery
• whether a liver transplant is needed

Chemotherapy is sometimes given before surgery to shrink the tumor and make it easier to remove. This is called neoadjuvant therapy.

After the doctor removes all the cancer that can be seen at the time of the surgery, some patients may be given chemotherapy or radiation therapy to kill any cancer cells that are left. Treatment given after the surgery, to lower the risk that the cancer will come back, is called adjuvant therapy.

Watchful waiting

Watchful waiting is closely monitoring a patient’s condition without giving any treatment until signs or symptoms appear or change. In hepatoblastoma, this treatment is only used for small well-differentiated fetal (pure fetal) histology tumors that have been completely removed by surgery.

Chemotherapy

Chemotherapy (also called chemo) uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Chemotherapy may be given alone or with other types of treatment, such as radiation therapy.

There are two ways to give chemotherapy to treat hepatoblastoma.

• Systemic chemotherapy is chemotherapy that is injected into a vein. When given this way, the drugs enter the bloodstream and can reach cancer cells throughout the body.
• Regional chemotherapy is chemotherapy that is placed directly into the cerebrospinal fluid, an organ, or a body cavity such as the abdomen. When given this way, the drugs mainly affect cancer cells in those areas.

  Chemoembolization of the hepatic artery (the main artery that supplies blood to the liver) is a type of regional chemotherapy used to treat hepatoblastoma that cannot be removed by surgery. The anticancer drug is injected into the hepatic artery through a catheter (thin tube). The drug is mixed with a substance that blocks the artery, cutting off blood flow to the tumor. Most of the anticancer drug is trapped near the tumor, and only a small amount of the drug reaches other parts of the body. The blockage may be temporary or permanent, depending on the substance used to block the artery. The tumor is prevented from getting the oxygen and nutrients it needs to grow. The liver continues to receive blood from the hepatic portal vein, which carries blood from the stomach and intestine to the liver. This procedure is also called transarterial chemoembolization, or TACE.

Chemotherapy drugs used to treat hepatoblastoma include:

• carboplatin
• cisplatin
• doxorubicin
• etoposide
• fluorouracil (5-FU)
• ifosfamide
• irinotecan
• vincristine

Combinations of these drugs may be used. Other chemotherapy drugs not listed here may also be used.

Radiation therapy

Radiation therapy uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. The way the radiation therapy is given depends on the type of the cancer being treated and the PRETEXT or POSTTEXT group.

Hepatoblastoma may be treated with external beam radiation therapy or internal radiation therapy.

• External radiation therapy uses a machine outside the body to send radiation toward the area of the body with cancer. External radiation therapy is used to treat hepatoblastoma that cannot be removed by surgery or has spread to other parts of the body.
• Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer.

  Radioembolization is a type of internal radiation therapy used to treat hepatoblastoma. A very small amount of a radioactive substance is attached to tiny beads that are injected into the hepatic artery (the main artery that supplies blood to the liver) through a thin tube called a catheter. The beads are mixed with a substance that blocks the artery, cutting off blood flow to the tumor. Most of the radiation is trapped near the tumor to kill the cancer cells. This is done to shrink the tumor or to relieve symptoms and improve quality of life for children with hepatoblastoma.

Radiofrequency ablation therapy

Radiofrequency ablation uses needles inserted directly through the skin or through an incision in the abdomen to reach the tumor. High-energy radio waves heat the needles and tumor, which kills cancer cells. Radiofrequency ablation is being used to treat recurrent hepatoblastoma.

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. Because cancer in children is rare, taking part in a clinical trial should be considered.

Targeted therapy

Targeted therapy uses drugs or other substances to block the action of specific enzymes, proteins, or other molecules involved in the growth and spread of cancer cells. Targeted therapy is being studied for the treatment of hepatoblastoma that has come back after treatment.

Treatment of newly diagnosed hepatoblastoma

Treatment options for newly diagnosed hepatoblastoma that can be removed by surgery at the time of diagnosis may include the following:

• surgery to remove the tumor, followed by combination chemotherapy, for hepatoblastoma that is mixed epithelial and fetal histology (not well-differentiated fetal histology) or aggressive chemotherapy for small cell undifferentiated histology
• surgery to remove the tumor, followed by watchful waiting or chemotherapy, for hepatoblastoma with well-differentiated fetal histology

Treatment options for newly diagnosed hepatoblastoma that cannot be removed by surgery or is not removed at the time of diagnosis may include the following:

• combination chemotherapy to shrink the tumor, followed by surgery to remove the tumor
• combination chemotherapy, followed by a liver transplant
• chemoembolization or radioembolization of the hepatic artery to shrink the tumor, followed by surgery to remove the tumor
• if the tumor in the liver cannot be removed by surgery, but there are no signs of cancer in other parts of the body, the treatment may be a liver transplant

For newly diagnosed hepatoblastoma that has spread to other parts of the body at the time of diagnosis, combination chemotherapy is given to shrink the tumors in the liver and cancer that has spread to other parts of the body. After chemotherapy, imaging tests are done to check whether the tumors can be removed by surgery.

Treatment options may include the following:

• If the tumors in the liver and other parts of the body (usually nodules in the lung) can be removed, surgery will be done to remove the tumors, followed by chemotherapy to kill any cancer cells that may remain.
• If the tumor in other parts of the body cannot be removed, or a liver transplant is not possible, chemotherapy, chemoembolization or radioembolization of the hepatic artery, or radiation therapy may be given.
• If the tumor in other parts of the body cannot be removed, or the patient does not want surgery, radiofrequency ablation may be given.

Treatment options in clinical trials for newly diagnosed hepatoblastoma include the following:

• a clinical trial of chemotherapy and surgery

Treatment of progressive or recurrent hepatoblastoma

Treatment of progressive or recurrent hepatoblastoma may include the following:

• surgery to remove isolated (single and separate) metastatic tumors with or without chemotherapy
• radiofrequency ablation
• combination chemotherapy
• liver transplant

Side effects and late effects of treatment

Problems from cancer treatment that begin 6 months or later after treatment and continue for months or years are called long-term or late effects. Late effects of cancer treatment may include the following:

• physical problems that affect liver function or hearing
• changes in mood, feelings, thinking, learning, or memory
• second cancers (new types of cancer)

Some late effects may be treated or controlled. It is important to talk with your child's doctors about the long-term effects cancer treatment can have on your child.

Follow-up care

As your child goes through treatment, they will have follow-up tests or checkups. Some of the tests that were done to diagnose the cancer or to find out the treatment group may be repeated 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.

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 child's condition has changed, or if the cancer has recurred (come back).

If your child has been diagnosed with hepatoblastoma, you may have questions about how serious the cancer is and your child's chances of survival. The likely outcome or course of a disease is called prognosis.

The prognosis for hepatoblastoma depends on the following:

• the PRETEXT group
• the size of the tumor
• whether the type of hepatoblastoma is well-differentiated fetal (pure fetal) or small cell undifferentiated histology
• whether the cancer has spread to other places in the body, such as the diaphragm, lungs, or certain large blood vessels
• whether there is more than one tumor in the liver
• whether the outer covering around the tumor has broken open
• how the cancer responds to chemotherapy
• whether the cancer can be removed completely by surgery
• whether your child can have a liver transplant
• whether the AFP blood levels go down after treatment
• your child's age
• whether the cancer has just been diagnosed or has come back after treatment

For hepatoblastoma that comes back after initial treatment, the prognosis depends on the following:

• where in the body the tumor recurred
• the type of treatment used to treat the initial cancer

Hepatoblastoma may be cured if the tumor is small and can be completely removed by surgery.

No two people are alike, and responses to treatment can vary greatly. Your child's cancer care team is in the best position to talk with you about your child's prognosis.