Childhood Liver Cancer Treatment Questions

Liver cancer in children is rare, and the words used to describe it are unfamiliar to almost every parent who hears them. PRETEXT. AFP. Resectability. This page explains what those terms mean and turns them into questions you can ask.

Hepatoblastoma is the most common type. NCI reports that roughly 90% of malignant liver tumors in children aged 4 years and younger are hepatoblastomas.

Cases have risen. NCI reports that the yearly rate went from 0.8 cases per 1 million children in 1975 to 1983, up to 2.3 cases per 1 million in 2020.

Other types exist, and they are treated differently. NCI lists childhood hepatocellular carcinoma, undifferentiated embryonal sarcoma, infantile choriocarcinoma, and fibrolamellar carcinoma.

The first question is simply which one it is. Ask for the exact name on the pathology report.

Alpha-fetoprotein (AFP) is a protein measured in blood. NCI describes it as a serum tumor marker, meaning a substance that can be raised when cancer is present. Beta-human chorionic gonadotropin (beta-hCG) is sometimes measured too.

AFP is not only a diagnosis test. It is a response test. NCI reports that the greatest response to chemotherapy comes after the first two cycles, judged by falls in tumor size and in AFP level.

Ask what the AFP was at diagnosis, what it is now, and what the team expects it to do after cycle two.

Surgeons divide the liver into four sections. PRETEXT groups describe how many of those sections contain tumor, and how many clean sections are left side by side. That matters because a surgeon needs enough healthy, connected liver to leave behind.

NCI defines the groups this way.

• Group I: one section involved; three adjoining sections are tumor free.
• Group II: one or two sections involved; two adjoining sections are tumor free.
• Group III: two or three sections involved; one adjoining section is tumor free.
• Group IV: four sections involved.

You may see both PRETEXT and POSTTEXT in reports. Ask which one your report shows and when the imaging was done.

NCI describes annotation factors, single letters added to the group. They describe blood vessels and spread.

• V: the tumor involves the retrohepatic vena cava, or all three major hepatic veins.
• P: the tumor involves the main portal vein, or both the right and left portal veins.
• E: disease has crossed tissue boundaries outside the liver.
• M: there are distant metastases.
• N: lymph nodes are abnormal.
• R: the tumor has ruptured, with free fluid and signs of bleeding.

These letters often decide whether a surgeon can operate or whether a transplant center needs to see the case. Ask which letters apply to your child.

NCI names three histology patterns that affect hepatoblastoma treatment:

• Well-differentiated fetal histology, also called pure fetal.
• Small cell undifferentiated histology, and rhabdoid tumors.
• Mixed epithelial and fetal histology that is not well differentiated.

The distinction is practical. NCI describes watchful waiting as an option only for small, well-differentiated fetal tumors that were removed at diagnosis. Every other pattern gets chemotherapy.

For small cell undifferentiated tumors, NCI describes testing of the SMARCB1 gene and immunohistochemistry to check for INI1 changes. Ask whether that testing was done.

Treatment follows from whether the tumor can be taken out.

Removable at diagnosis. NCI describes partial hepatectomy, surgery to remove the affected part of the liver, followed by combination chemotherapy. For pure fetal histology, watchful waiting may replace chemotherapy.

Not removable at diagnosis. NCI lists three routes: chemotherapy first to shrink the tumor and then surgery; chemotherapy and then liver transplant; or chemoembolization or radioembolization first, then surgery.

With metastases. Chemotherapy first, with imaging afterward to see whether surgery has become possible.

Progressive or recurrent. Options include surgery for isolated metastases, radiofrequency ablation, combination chemotherapy, and liver transplant.

Ask directly: is this tumor resectable today, and if not, what specific change would make it resectable?

Transplant is a real option, not a last resort, and outcomes are documented.

For hepatoblastoma, NCI reports a 5-year patient survival rate after liver transplant of 73%, with a graft survival rate of 74%. For transplants performed between 2009 and 2012, the 3-year patient and graft survival rates were both 84%.

For hepatocellular carcinoma, NCI reports 63% 5-year survival, and 85% at 3 years for the 2009 to 2012 group.

Ask when a transplant center will review the case. Ask whether the referral has already been made, and by whom. A transplant assessment takes time that a growing tumor does not always allow.

NCI lists the chemotherapy drugs used for childhood liver cancer: carboplatin, cisplatin, doxorubicin, etoposide, fluorouracil, ifosfamide, irinotecan, and vincristine.

Cisplatin is central to hepatoblastoma treatment, and it damages hearing. NCI reports that cisplatin causes permanent hearing loss in up to 75% of children who receive it, and notes that hearing loss in a child can cause delays in learning and in social and emotional development.

Sodium thiosulfate lowers that risk. The FDA approved it for children aged 1 month through 18 years with localized tumors, meaning cancer that has not spread beyond the tissue or organ where it began. In a Children's Oncology Group trial, 44% of children given sodium thiosulfate developed hearing loss compared with 58% of those who were not. NCI notes that more research is needed before it is used when cancer has already spread.

Ask whether sodium thiosulfate applies to your child, and ask for a baseline hearing test before the first cisplatin dose.

Your child is on drugs with specific warnings, and one sign cannot wait.

• Call your child's care team immediately, day or night, if your child's temperature reaches 100.4°F (38°C) or higher at any point during chemotherapy. CDC calls fever during chemotherapy a medical emergency, because it may be the only sign of an infection that can turn life-threatening within hours. If you cannot reach the team quickly, take your child to an emergency department and say straight away that they are on chemotherapy.
• Call 911 or go to an emergency department if your child is breathing fast or with difficulty, is floppy, grey or mottled, cannot be woken properly, has a seizure, or has sudden severe belly pain with a hard, swollen abdomen, which can mean the tumor has bled.
• Call your care team the same day if your child passes much less urine than usual, swells in the face, hands, feet or lower legs, is unusually tired, or reports hearing loss, ringing in the ears or dizziness. MedlinePlus lists all of these as reasons to contact the doctor right away on cisplatin.
• Call your care team within a day or two if your child is off their food, losing weight, or bruising more easily than before.

Ask the team for their own written list and the number to call at night and on weekends.

NCI links hepatoblastoma to Beckwith-Wiedemann syndrome, hemihyperplasia, familial adenomatous polyposis, glycogen storage disease, trisomy 18, and Aicardi syndrome. Very low birth weight prematurity is also linked; NCI cites a 15-fold increase in risk in Japan.

Screening for at-risk children is specific. NCI describes an abdominal ultrasound every 3 months, from birth or from the date a risk factor is found, until the child is 4 years old, along with AFP blood tests.

If a syndrome is found in your child, ask whether other children in the family need this screening.

• What is the exact tumor type and histology on the pathology report?
• What is the PRETEXT group, and which annotation letters apply?
• Is the tumor resectable now? If not, what would have to change?
• Has a transplant center reviewed the case, and when?
• What was the AFP at diagnosis, and what should it be after two cycles?
• Which drugs, how many cycles, and what is the total cisplatin dose?
• Is sodium thiosulfate part of the plan?
• When is the baseline hearing test, and how often afterward?
• How will kidney function, nutrition, and growth be tracked?
• Which syndrome testing has been done, and does it change sibling screening?

• Hepatoblastoma — National Cancer Institute.
• Childhood Liver Cancer Treatment (PDQ) Health Professional Version — National Cancer Institute.
• Childhood Liver Cancer — National Cancer Institute.
• Sodium Thiosulfate Reduces Hearing Loss in Kids with Cancer — National Cancer Institute.
• Cisplatin Injection — MedlinePlus.
• Fever and Cancer Treatment — Centers for Disease Control and Prevention.