Hepatoblastoma is a rare liver cancer that affects very young children, most often before their third birthday. While the diagnosis can be overwhelming for families, modern treatment approaches combining chemotherapy and surgery have transformed outcomes dramatically over the past few decades. Understanding the treatment options available, from standard therapies to innovative approaches being tested in clinical trials, can help families navigate this challenging journey with greater confidence.

How Treatment Works to Fight Liver Cancer in Children

When a child receives a diagnosis of hepatoblastoma, the main goal of treatment is to remove all cancer cells from their body while preserving as much healthy liver tissue as possible. This is different from simply managing symptoms — the medical team works to eliminate the cancer completely. The liver has a remarkable ability to regenerate, meaning it can grow back after parts of it are removed during surgery. This quality makes surgical removal of tumors more feasible than with many other organs.^[1]

Treatment plans are carefully tailored to each child’s specific situation. The stage of the disease, the size and location of the tumor, whether it has spread to other parts of the body, and your child’s overall health all influence which treatments doctors recommend. Children with small tumors in just one part of the liver may need different treatment than those with larger tumors affecting multiple sections or those whose cancer has spread to the lungs. Age also matters — very young infants may respond differently to certain medications than older toddlers.^[2]

Medical professionals use two main staging systems to classify hepatoblastoma. The PRETEXT system (pre-treatment extent of disease) looks at imaging scans taken before any treatment starts to determine how many lobes of the liver contain tumor. The liver has four main sections, and whether one, two, three, or all four sections are involved helps doctors plan the best approach. The Children’s Oncology Group staging system looks at whether the tumor can be completely removed surgically and whether cancer has spread beyond the liver.^[4]

Over the past thirty years, survival rates for children with hepatoblastoma have improved dramatically. In the 1970s, only about 30% of children survived this cancer. Today, with modern treatment combining chemotherapy and surgery, approximately 70% to 90% of children can be cured, depending on the stage at diagnosis. This remarkable improvement comes from collaborative research by medical centers around the world working together to find better treatments.^[5]

Standard Treatment Approaches for Hepatoblastoma

The cornerstone of hepatoblastoma treatment involves two main components: chemotherapy (medications that kill cancer cells) and surgery (physically removing the tumor from the liver). Most children receive both types of treatment, though the order and intensity depend on individual circumstances.

For children whose tumors are small and located in just one or two sections of the liver at diagnosis, doctors may perform surgery first to remove the tumor right away. This approach works best when the tumor can be completely removed without damaging too much healthy liver tissue. After surgery, these children typically receive chemotherapy to eliminate any remaining cancer cells that might be too small to see on scans. Research has shown that children with completely removed tumors who receive just two cycles of chemotherapy after surgery can achieve excellent results, with survival rates above 90%.^[12]

However, many children have larger tumors or tumors in difficult locations that cannot be safely removed at diagnosis. For these children, treatment begins with chemotherapy given before surgery — this is called neoadjuvant chemotherapy. The chemotherapy works to shrink the tumor, making it smaller and easier to remove safely during surgery later. European medical groups pioneered this approach and demonstrated that giving chemotherapy first significantly improves surgical outcomes. After several months of chemotherapy, when the tumor has shrunk sufficiently, surgeons can remove it more easily and safely.^[12]

The most effective chemotherapy medications for hepatoblastoma are cisplatin and doxorubicin. Cisplatin is considered the single most active drug against this cancer. Medical trials have compared different combinations of chemotherapy drugs to find the best balance between effectiveness and side effects. One commonly used regimen combines cisplatin with fluorouracil (5-FU) and vincristine. This three-drug combination has proven as effective as more toxic combinations while causing fewer serious side effects. Another effective combination uses cisplatin with doxorubicin.^[12]

The duration of chemotherapy treatment varies but typically involves multiple cycles spread over several months. Children receiving neoadjuvant chemotherapy before surgery usually get several cycles first, then have surgery, followed by additional cycles after surgery. The exact number of cycles depends on how well the tumor responds and the stage of disease. Throughout treatment, doctors monitor blood tests carefully to ensure the chemotherapy is working and to watch for side effects.^[6]

For some children, even after chemotherapy shrinks the tumor, it cannot be completely removed because of its size or location, or because it involves too much of the liver. In these cases, liver transplantation may be necessary. This involves removing the entire diseased liver and replacing it with a healthy liver from a donor. Liver transplantation has become an important treatment option and can provide cure rates around 80% for children who otherwise would have no other surgical option. The procedure requires finding a suitable donor liver and lifelong medications to prevent rejection, but it can be lifesaving.^[3]

Surgical techniques for removing liver tumors have advanced significantly. Surgeons may perform different types of operations depending on tumor location. A segmentectomy removes just a small segment of the liver. A lobectomy removes a larger section (lobe). Extended hepatectomy removes multiple sections. Because the liver can regenerate, even when large portions are removed, the remaining liver tissue can grow back to nearly normal size within weeks to months after surgery.^[9]

Side Effects of Standard Treatment

Chemotherapy medications work by attacking rapidly dividing cells, which includes cancer cells but also some normal cells in the body. This can cause various side effects. Common side effects of chemotherapy for hepatoblastoma include nausea, vomiting, loss of appetite, fatigue, increased risk of infections (because chemotherapy temporarily lowers white blood cell counts), hair loss, and mouth sores. Most of these side effects are temporary and resolve after treatment ends.^[1]

Cisplatin, while very effective against hepatoblastoma, can cause specific long-term side effects. One of the most concerning is ototoxicity, which means damage to hearing. Some children develop hearing loss during or after cisplatin treatment. This hearing damage may be permanent and can affect speech development and learning. For this reason, children receiving cisplatin have their hearing tested regularly during and after treatment. Researchers have been exploring whether carboplatin, a related drug with less hearing damage risk, could replace cisplatin, though studies have not yet proven it equally effective.^[12]

Cisplatin can also affect kidney function, so children receive extra fluids before and after each dose to protect their kidneys. Regular blood tests monitor kidney function throughout treatment. Doxorubicin can affect heart function, so doctors monitor the heart with tests called echocardiograms during and after treatment. These precautions help catch potential problems early when they can be addressed.^[5]

Surgery carries its own risks, including bleeding, infection, and complications from anesthesia. Because liver surgery is complex, it should ideally be performed at specialized centers with experienced pediatric surgeons who regularly perform these operations. After surgery, children need careful monitoring as their liver regenerates. For those who undergo liver transplant, anti-rejection medications must be taken for life, and these drugs carry their own side effects including increased infection risk and potential kidney problems.^[17]

Innovative Treatments Being Tested in Clinical Trials

While standard treatment achieves good results for many children with hepatoblastoma, researchers continue searching for better approaches, especially for children with high-risk features or cancer that doesn’t respond well to current treatments. Clinical trials are carefully controlled research studies that test new treatments before they become standard practice. These trials happen in three phases: Phase I tests whether a new treatment is safe and determines the right dose; Phase II tests whether it works against the cancer; and Phase III compares the new treatment to current standard treatment to see if it’s better.^[2]

One area of active research involves understanding the molecular biology of hepatoblastoma — the genetic changes that make liver cells become cancerous. Scientists have discovered that mutations in the Wnt signaling pathway, particularly involving a protein called beta-catenin, occur in up to 67% of hepatoblastoma cases. This pathway normally helps control cell growth and division. When mutations activate this pathway inappropriately, cells grow out of control. Understanding these molecular changes helps researchers develop targeted therapies that specifically attack cancer cells with these mutations while sparing normal cells.^[5]

Another molecular finding involves telomerase, an enzyme that affects cell aging. Aggressive hepatoblastomas often show activation of TERT (human telomerase reverse transcriptase), which allows cancer cells to divide indefinitely without aging. Researchers are exploring whether drugs that inhibit telomerase could help treat these aggressive tumors.^[5]

Several innovative treatment approaches are being investigated in clinical trials for hepatoblastoma. Radioembolization, also called Y90 therapy, delivers high-dose radiation directly to liver tumors through the bloodstream. A radiologist inserts a tiny tube (catheter) through the groin and guides it to the artery closest to the tumor. Tiny radioactive spheres are then released, which lodge in the tumor’s blood vessels and deliver targeted radiation. This approach protects normal liver tissue from radiation damage while intensely treating the tumor. Y90 can be used when tumors don’t respond well to chemotherapy or when they come back after initial treatment.^[7]

Another targeted approach is transarterial chemoembolization (TACE). Similar to Y90, this technique uses a catheter guided to the tumor’s blood supply. Chemotherapy drugs are injected directly into the artery feeding the tumor, along with substances that block the blood vessel. This delivers high concentrations of chemotherapy directly to the cancer while cutting off its blood supply, causing tumor cells to die. Because the drugs are concentrated in the tumor rather than circulating throughout the body, TACE can deliver stronger doses to the cancer while causing fewer body-wide side effects.^[7]

Researchers are also investigating whether certain combinations of chemotherapy drugs work better than others. Some studies are testing whether adding other drugs to the standard cisplatin-based regimens could improve outcomes for children with high-risk disease. For example, trials have explored alternating different platinum-containing drugs, though results showed that intensifying treatment this way increased toxicity without improving survival for most children.^[12]

International collaboration has become increasingly important in hepatoblastoma research. Because this cancer is so rare, no single hospital or even single country sees enough cases to conduct large studies alone. The Children’s Hepatic Tumors International Collaboration (CHIC) brings together major study groups from North America, Europe, and Japan. This collaboration merged data from 1,605 children treated in multiple clinical trials to better understand which factors predict outcomes. This global database helps researchers design better risk stratification systems — ways to predict which children need more intensive treatment and which can safely receive less toxic therapy. Such collaboration accelerates progress toward better treatments.^[16]

Clinical trials for hepatoblastoma are available at specialized pediatric cancer centers, particularly those affiliated with cooperative groups like the Children’s Oncology Group in North America, SIOP (International Society for Paediatric Oncology) in Europe, and similar organizations in Asia. Families whose children have hepatoblastoma should ask their medical team whether any clinical trials might be appropriate for their child’s situation. Participating in a clinical trial gives children access to potentially better treatments while contributing to medical knowledge that will help future children with this cancer.^[13]

Most common treatment methods

• Neoadjuvant chemotherapy
  • Chemotherapy given before surgery to shrink large tumors and make them easier to remove safely
  • Typically uses cisplatin combined with other drugs like fluorouracil and vincristine, or cisplatin with doxorubicin
  • Usually involves several cycles over months before attempting surgical removal
  • Has significantly improved outcomes for children with initially unresectable tumors
• Surgical resection
  • Complete removal of the tumor is essential for curing hepatoblastoma
  • May involve removing just a segment, a lobe, or multiple sections of the liver depending on tumor extent
  • Can be performed upfront for small, localized tumors or after chemotherapy shrinks larger tumors
  • The liver’s regenerative ability allows it to grow back after even large portions are removed
• Adjuvant chemotherapy
  • Chemotherapy given after surgery to eliminate any remaining microscopic cancer cells
  • Children with completely resected tumors at diagnosis may need only two cycles of postoperative chemotherapy
  • Usually started about four weeks after surgery to allow liver healing
  • Helps prevent cancer recurrence
• Liver transplantation
  • Removing the entire diseased liver and replacing it with a healthy donor liver
  • Used when tumors cannot be completely removed by standard surgery even after chemotherapy
  • Provides cure rates around 80% for otherwise unresectable tumors
  • Requires lifelong anti-rejection medications
• Radioembolization (Y90)
  • Delivers high-dose radiation directly to liver tumors through tiny radioactive spheres injected into tumor blood vessels
  • Used when tumors don’t respond well to chemotherapy or recur after initial treatment
  • Protects normal liver tissue while intensely treating the tumor
  • Performed by interventional radiologists using catheter-based techniques
• Transarterial chemoembolization (TACE)
  • Delivers concentrated chemotherapy directly to the tumor through its blood supply
  • Also blocks blood vessels feeding the tumor, cutting off its nutrient supply
  • Allows higher chemotherapy doses to the cancer with fewer body-wide side effects
  • Used for tumors resistant to standard chemotherapy or as additional treatment