Hepatoblastoma

Changes in the genes inside our cells can increase the risk of certain health problems, such as some types of cancer. These changes can be inherited from a parent or sometimes can happen very early in development before a child is born.

People with certain family cancer syndromes have a higher risk of developing hepatoblastoma. The syndromes most strongly linked to hepatoblastoma are:

• Beckwith-Wiedemann syndrome
• Familial adenomatous polyposis
• Simpson-Golabi-Behmel syndrome
• Trisomy 18 (Edwards syndrome)

Other conditions have also been linked to hepatoblastoma, though the connection is not as strong:

• Neurofibromatosis type 1
• Prader-Willi syndrome
• Trisomy 13 (Patau syndrome)
• Trisomy 21 (Down syndrome)
• Aicardi syndrome
• Li-Fraumeni syndrome
• Goldenhar syndrome
• Glycogen storage diseases
• Sotos syndrome
• Noonan syndrome

In some of these conditions, screening for hepatoblastoma with blood or imaging tests may be recommended when children are young.

Factors outside our bodies can increase the risk of some types of cancer. Unlike many adult cancers, lifestyle-related risk factors, such as physical activity, diet, and the use of substances do not play a major role in pediatric cancers.

Hepatoblastoma is more common in children who:

• Were born early (premature)
• Had a low birth weight
• Have birth defects, such as heart, kidney, or bladder abnormalities

The reason for this is not entirely known.

Imaging tests use x-rays, sound waves, or magnetic fields to create pictures of the inside of the body. Imaging tests can be done for a few reasons, including:

• To help find out if a suspicious area might be cancer
• To learn how far cancer has spread
• To help determine if treatment is working

A liver mass might first be found on an ultrasound, but often more detailed imaging, such as a CT scan or an MRI is needed. Other imaging tests, such as a chest x-ray or CT scan, might be used to look for cancer spread in the lungs or other places.

Blood tests can look for AFP (alpha-fetoprotein), a protein that many hepatoblastoma cells make. The normal level of AFP can change with a child’s age. But if a child has a liver mass and an elevated level of AFP for their age, this can be a sign of hepatoblastoma.

If the AFP level is normal, the tumor might be a different type of liver cancer. A biopsy is often still needed to be sure.

In rare cases, hepatoblastoma tumors can make a protein called hCG (human chorionic gonadotropin), which can also be measured in the blood. This protein can cause hair growth, usually seen in puberty, in much younger children.

Your care team may also do other blood tests to check how well the liver and kidneys are working. They might also check blood cell counts or run clotting tests before a biopsy or surgery.

To confirm a diagnosis of hepatoblastoma, a biopsy is usually done. In this procedure, a small sample of tissue is removed and looked at under a microscope. In some cases, if the tumor is smaller and far enough away from major blood vessels, the entire tumor may be removed instead of taking only a sample.

This procedure is done under anesthesia, while the child is asleep.

Hepatoblastoma staging can be described using imaging test results to define a PRETEXT or POSTTEXT group.

A hepatoblastoma tumor is given a group classification based on imaging tests either at the time of diagnosis (PRETEXT) or after initial chemotherapy (POSTTEXT).

The 4 tumor groups are based on how many of the liver’s 4 sections are involved:

• Group I: The tumor is in 1 section.
• Group II: The tumor is in 2 sections, with 2 neighboring sections free of tumor.
• Group III: The tumor is in 3 sections, with no 2 neighboring sections free of tumor.
• Group IV: The tumor is in all 4 sections.

There are a few different risk grouping systems for hepatoblastoma around the world. Most recently, the Children’s Hepatic tumors International Collaboration (CHIC) introduced a standardized risk stratification tool based on factors such as:

• The PRETEXT stage
• Annotation factors (letters above)
• How old the child is when the tumor is diagnosed
• The AFP level

Based on this information, hepatoblastoma can be divided into 4 risk groups:

• Very low risk
• Low risk
• Intermediate risk
• High risk

Risk groups are used by the cancer care team to understand the outlook and decide which treatment options are best.

Surgery is the preferred treatment for hepatoblastoma when the tumor can be removed safely at the time of diagnosis.

If the tumor cannot be removed safely right away, chemotherapy might be given first to shrink the tumor. Surgery may then be done later to remove the tumor.

A liver transplant might also be an option when the tumor is large and cannot be removed by taking out only part of the liver. This might be considered if the cancer is limited to the liver or if any cancer that has spread outside the liver has been treated completely.

For more information, see Surgery for Liver Cancer.

In most cases, chemotherapy in combination with surgery is needed to prevent cancer from coming back (recurrence). However, in the case of well-differentiated fetal hepatoblastoma, surgery to remove the tumor may be all that is needed.

Chemotherapy (chemo) is the use of drugs to treat cancer. Chemo drugs used to treat hepatoblastoma can include:

• 5-Fluorouracil (5-FU)
• Carboplatin
• Cisplatin
• Doxorubicin
• Etoposide
• Irinotecan
• Vincristine

Chemo drugs can be used alone or in combination, depending on the tumor and its risk of coming back after treatment.

For example, a combination called C5VD may be used in children with intermediate-risk hepatoblastoma. C5VD combines cisplatin, 5-fluorouracil, vincristine, and doxorubicin.

Chemotherapy might be used before surgery, after surgery, or both.

Side effects of chemotherapy

Chemo drugs can cause side effects. These depend on the type and dose of drugs given, and the length of treatment. Common side effects include:

• Nausea and vomiting
• Loss of appetite
• Diarrhea
• Hair loss
• Mouth sores

Chemo can also affect the blood-forming cells of the bone marrow, which can lead to:

• Increased chance of infections (from low white blood cell counts, also called leukopenia)
• Easy bruising or bleeding (from low blood platelet counts, also called thrombocytopenia)
• Fatigue (from low red blood cell counts and other reasons, also called anemia)

During treatment, tell your cancer care team about any side effects your child is having. There are often ways to shorten or lessen side effects. For example, growth factors may be given after chemotherapy to help the white blood cell count improve sooner. Certain medicines for nausea and vomiting can prevent or reduce these side effects.

These side effects often go away after treatment is finished. But some chemo drugs may have long-term or even permanent side effects:

• Cisplatin can cause kidney damage. To help prevent this, doctors give lots of IV fluid before and after this drug is given.
• Cisplatin, carboplatin, and vincristine can cause nerve damage (neuropathy). This can lead to problems with numbness, tingling, or even pain in the hands and feet.
• Cisplatin can damage the nerves in the ear, which may lead to hearing loss. To help protect against this, a drug called sodium thiosulfate (STS) is sometimes given along with cisplatin.
• Doxorubicin can cause damage to the heart. To help protect against this, a drug called dexrazoxane is often given. The cancer care team will monitor heart function during and after treatment, and the total dose of this drug may be limited to reduce this risk.

Other drugs can have other side effects, so ask about what side effects to expect from the treatments your child will receive.

The cancer care team will watch closely for side effects, treat them, and adjust chemo doses if needed.

Radiation therapy uses high-energy rays to kill cancer cells.

Radiation is not often used to treat hepatoblastoma, but it might be used in specific circumstances, such as if a tumor cannot be removed completely with surgery.

For children with tumors that cannot be removed with surgery and have not responded well to other treatments, other procedures might be an option, including:

• Transarterial chemoembolization (TACE)
• Transarterial radioembolization (TARE)

In these procedures, radiation or chemotherapy is given at high doses directly to the tumor. This helps block the tumor’s blood supply and cause it to shrink. These procedures are done more commonly in adults but are being studied for use in children.

For more information, see Embolization Therapy for Liver Cancer.

A relative survival rate compares people who have the same type and stage of hepatoblastoma to people in the overall population.

For example, if the 5-year relative survival rate for a specific type and stage of cancer is 90%, it means that, on average, people with that cancer are about 90% as likely to live for at least 5 years after being diagnosed, compared to people who don’t have that cancer. Of course, many children live much longer than 5 years after hepatoblastoma treatment.

Relative survival rates differ based on the size and location of the tumor when it is diagnosed.

For children with hepatoblastoma localized to the liver, survival rates are above 80% to 90% with a combination of surgery (either removal of the tumor or liver transplantation if removal is not possible) and chemotherapy.

For children with metastatic hepatoblastoma, survival rates are lower. However, outcomes are better with recent advances in treatment.