Improving Prognosis in Hepatoblastoma: Evolving Risk Stratification and Treatment Strategies

Introduction
Hepatoblastoma accounts for most pediatric liver cancers, but accounts for only 1% of all malignancies in children. Rates of hepatoblastoma have increased gradually over the past 20 years for unclear reasons, but it remains a rare malignancy. In the 1970s, only a small percentage of patients survived long-term. Today, 5-year survival rates range from 65% to over 90%, depending on risk factors, thanks to recent advancements in the understanding and treatment of hepatoblastoma.^1-5 Improved risk stratification has led to better staging and more personalized treatment approaches. To further improve survival, current research is concentrated on improving outcomes in the most challenging patient subsets, such as those with metastatic disease and patients with disease relapse.

Background
Hepatoblastoma is typically diagnosed in the first 2 years of life.⁶ Accounting for more than 60% of pediatric hepatic malignancies worldwide, the incidence of hepatoblastoma is increasing. Results from a study evaluating the incidence between 2001 and 2017 showed a 2% annual increase documented in children aged from birth to 4 years in the United States, climbing to 5.8% annually among children aged 5 to 9 years.² Risk factors for hepatoblastoma include maternal preeclampsia, premature birth, and parental smoking.⁷ The degree to which each of these factors plays a role is uncertain. A genetic etiology is suspected in a minority of hepatoblastoma cases, but it is associated with several genetic diseases, including Beckwith-Weidemann syndrome, familial adenomatous polyposis, and Prader-Willi syndrome.⁸ Genetic mutations in the Wnt signaling pathway that result in the accumulation of beta-catenin have also been found in sporadic, nonfamilial cases.⁹

Although this condition generally presents as a single abdominal mass in the right lobe of the liver, multifocal hepatoblastoma at diagnosis does occur.¹⁰ In most patients, alpha-fetoprotein (AFP) is significantly elevated.¹¹ An estimated 20% of patients present with metastases, which are most commonly found in the lung.¹² While ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI) can be used to define the extent of the tumor in the liver, a chest CT is appropriate to look for metastases beyond the liver.¹³

Of the 2 broad histological categories commonly used to characterize hepatoblastoma, the more common epithelial form consists of fetal or embryonal liver cells. The mixed epithelial-mesenchymal form that accounts for 20% to 30% of hepatoblastomas features epithelial and primitive mesenchymal tissue, often with osteoid tissue or cartilage⁶; both have numerous histological subtypes. For example, the epithelial type can be further characterized by a well- or poorly-differentiated appearance, while the mixed type can be subdivided by the presence or absence of teratoid features.

Prior to 2017, there was considerable disparity in the way hepatoblastomas were characterized and staged among the major research consortiums. This issue was addressed when a consortium was established in which pediatric oncology groups pooled their data. The Children’s Hepatic tumors International Collaboration (CHIC) released the PRETEXT (PRETreatment EXTent of disease) approach.^7,14 Based on comprehensive data from 1605 children participating in multicenter trials, the CHIC risk stratification defines and provides risk trees for very low-, low-, intermediate-, and high-risk groups. The most important predictors included AFP levels, patient age, extent of disease in the liver (particularly involving major hepatic veins), and the presence of metastases.

Further improvements to the diagnosis and staging of hepatoblastoma are credited to consensus-based recommendations for imaging that were created in the context of the PRETEXT staging system.¹³ While ultrasound is recommended for the initial approach to diagnosis, this consensus calls for MRI with hepatobiliary contrast to better characterize the lesion and detect satellite lesions. This form of imaging is also recommended for follow-up after treatment, but results should be interpreted in the context of biomarkers, such as AFP levels, pathologic grading, and tumor subtypes.

In patients with the most common familial disorders associated with a predisposition for hepatoblastoma, such as adenomatous polyposis, Beckwith-Weidemann spectrum, or trisomy 18, regular surveillance for hepatoblastoma is recommended during the early years of life.⁸ Characterization of the genetic and molecular features of patients who present with hepatoblastoma might be useful in determining prognosis. Of genetic features, mutations in the CTNNB1 gene are the most common, but several genes in the Wnt pathway are also linked to hepatoblastoma formation.⁹

Along with the progress in subtyping patients by genetics, epigenetics, and molecular features, there is a growing appreciation for the heterogeneity of hepatoblastoma and the likelihood that treatment strategies can be better individualized to improve outcomes in high-risk patients. This progress is expected to accelerate further when results from the results from the Pediatric Hepatic International Tumor Trial (PHITT) are published. These data are expected to be available in 2025, and may help with prognostication and understanding the biology of hepatoblastoma in relation to outcomes.

Treatment Strategies in Hepatoblastoma
For low-grade hepatoblastoma, the first-line therapy is surgery, which can be sufficient for cure without relapse in selected patients with PRETEXT group 1 disease. Although only 40% to 60% of patients have resectable disease at diagnosis,¹⁰ there are several strategies to shrink tumor bulk, particularly chemotherapy due to the relatively high sensitivity of hepatoblastoma to cytotoxic therapies. The intensity of chemotherapy is increased relative to risk.¹¹ For example, cisplatin-based regimens are considered for low-risk patients, while additional therapies, such as doxorubicin, irinotecan, or both, are added in patients at higher risk. Cure is common if these regimens permit a margin-free resection, although relapse does occur in a subset of patients.

If adequate debulking of the tumor cannot be achieved with conventional surgery, liver transplantation is typically offered for patients without extrahepatic disease or after distant metastases have been successfully excised. With liver transplantation and combination therapies to inhibit relapse associated with seeding, long-term survival rates of 80% have been reported.³ Judicious use of transplantation in patients with high-risk disease that raises the potential for relapse has been credited with rates of long-term survival that exceed 80% in some series. However, there is concern of offering transplantation when it is not necessary. In patients who are high risk with multiple lesions in the liver, there is a general agreement that transplantation reduces the likelihood of subsequent relapse; however, as the precision of aggressive resection coupled with effective chemotherapy has improved, there are more patients in whom the optimal choice might not be debated by experts.

Review articles typically cite the likelihood of an overall 5-year survival in patients with hepatoblastoma as being on the order of 80%.¹ This rate includes children with late-onset disease, which is generally associated with a worse prognosis, and patients who eventually experience disease relapse. Survival rates are now likely to be substantially higher, with progress developing better treatment protocols for both groups. In the absence of high-risk features, long-term survival rates of 90% or higher are now being reported in some centers with high relative volumes of hepatoblastoma, regardless of baseline risks. 

PHITT
The rarity of hepatoblastoma poses a significant challenge to conducting prospective studies with sufficient sample sizes to evaluate the overall efficacy of treatments and their effectiveness in patient subgroups based on specific clinical characteristics and disease severity. PHITT is the first international collaborative liver tumors trial to use a consensus approach. Centers in Europe, Japan, and the United States are participating through regional cancer study consortia. The Cincinnati Children’s Hospital and Medical Center, a leader in hepatoblastoma management in the United States, is anchoring this effort for the Children’s Oncology Group. 

In addition to assessing treatment strategies in larger patient cohorts, PHITT is expanding the data available to correlate outcomes across different stages and risk categories based on histological and biological classifications. Hepatoblastoma and hepatocellular carcinoma are being addressed in PHITT, but the design schema for these malignancies differs. For patients enrolled with hepatoblastoma, 4 risk groups have been defined, ranging from very low to high. Within these risk categories, flow charts provide guide selection of treatments based on clinical and disease features.

Cincinnati Children’s Hospital and Medical Center is one of the most active centers for the treatment of hepatoblastoma in the Unites States but manages only 15 to 20 cases of this rare disease per year. PHITT is expected to play a critical role in achieving a high level of valuable data, and the first sets of outcomes from this collaboration are anticipated to be available in early 2025. As the study progresses, meaningful data are expected for the most challenging and some of the rarest hepatoblastoma risk groups.

Summary
The rates of cure are now approaching 100% with surgery and chemotherapy in patients with localized or locally advanced hepatoblastoma. For more advanced, unresectable disease, liver transplantation is effective in most patients, providing high rates of long-term survival. For patients with relapsed disease, advanced treatment protocols at centers with high relative volumes
of hepatoblastoma are now regularly achieving a second remission—many of which are durable. Although prognosis is less favorable in patients who experience a second relapse, long-term survival is achieved even in a proportion of these children. Substantial rates of response and long-term survival have been common in hepatoblastoma diagnosed at early stages, but the recent progress in advanced hepatoblastoma is credited to more aggressive therapies based on a better understanding of the disease characteristics that allows for individualized therapy. There is hope that the larger pool of data becoming available in 2025 from PHITT will prove to be an additional source of information that guides further advances in managing this rare disease.

Read more from the 2024 Rare Diseases Report: Hematology and Oncology.

Introduction
Hepatoblastoma accounts for most pediatric liver cancers, but accounts for only 1% of all malignancies in children. Rates of hepatoblastoma have increased gradually over the past 20 years for unclear reasons, but it remains a rare malignancy. In the 1970s, only a small percentage of patients survived long-term. Today, 5-year survival rates range from 65% to over 90%, depending on risk factors, thanks to recent advancements in the understanding and treatment of hepatoblastoma.^1-5 Improved risk stratification has led to better staging and more personalized treatment approaches. To further improve survival, current research is concentrated on improving outcomes in the most challenging patient subsets, such as those with metastatic disease and patients with disease relapse.

Background
Hepatoblastoma is typically diagnosed in the first 2 years of life.⁶ Accounting for more than 60% of pediatric hepatic malignancies worldwide, the incidence of hepatoblastoma is increasing. Results from a study evaluating the incidence between 2001 and 2017 showed a 2% annual increase documented in children aged from birth to 4 years in the United States, climbing to 5.8% annually among children aged 5 to 9 years.² Risk factors for hepatoblastoma include maternal preeclampsia, premature birth, and parental smoking.⁷ The degree to which each of these factors plays a role is uncertain. A genetic etiology is suspected in a minority of hepatoblastoma cases, but it is associated with several genetic diseases, including Beckwith-Weidemann syndrome, familial adenomatous polyposis, and Prader-Willi syndrome.⁸ Genetic mutations in the Wnt signaling pathway that result in the accumulation of beta-catenin have also been found in sporadic, nonfamilial cases.⁹

Although this condition generally presents as a single abdominal mass in the right lobe of the liver, multifocal hepatoblastoma at diagnosis does occur.¹⁰ In most patients, alpha-fetoprotein (AFP) is significantly elevated.¹¹ An estimated 20% of patients present with metastases, which are most commonly found in the lung.¹² While ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI) can be used to define the extent of the tumor in the liver, a chest CT is appropriate to look for metastases beyond the liver.¹³

Of the 2 broad histological categories commonly used to characterize hepatoblastoma, the more common epithelial form consists of fetal or embryonal liver cells. The mixed epithelial-mesenchymal form that accounts for 20% to 30% of hepatoblastomas features epithelial and primitive mesenchymal tissue, often with osteoid tissue or cartilage⁶; both have numerous histological subtypes. For example, the epithelial type can be further characterized by a well- or poorly-differentiated appearance, while the mixed type can be subdivided by the presence or absence of teratoid features.

Prior to 2017, there was considerable disparity in the way hepatoblastomas were characterized and staged among the major research consortiums. This issue was addressed when a consortium was established in which pediatric oncology groups pooled their data. The Children’s Hepatic tumors International Collaboration (CHIC) released the PRETEXT (PRETreatment EXTent of disease) approach.^7,14 Based on comprehensive data from 1605 children participating in multicenter trials, the CHIC risk stratification defines and provides risk trees for very low-, low-, intermediate-, and high-risk groups. The most important predictors included AFP levels, patient age, extent of disease in the liver (particularly involving major hepatic veins), and the presence of metastases.

Further improvements to the diagnosis and staging of hepatoblastoma are credited to consensus-based recommendations for imaging that were created in the context of the PRETEXT staging system.¹³ While ultrasound is recommended for the initial approach to diagnosis, this consensus calls for MRI with hepatobiliary contrast to better characterize the lesion and detect satellite lesions. This form of imaging is also recommended for follow-up after treatment, but results should be interpreted in the context of biomarkers, such as AFP levels, pathologic grading, and tumor subtypes.

In patients with the most common familial disorders associated with a predisposition for hepatoblastoma, such as adenomatous polyposis, Beckwith-Weidemann spectrum, or trisomy 18, regular surveillance for hepatoblastoma is recommended during the early years of life.⁸ Characterization of the genetic and molecular features of patients who present with hepatoblastoma might be useful in determining prognosis. Of genetic features, mutations in the CTNNB1 gene are the most common, but several genes in the Wnt pathway are also linked to hepatoblastoma formation.⁹

Along with the progress in subtyping patients by genetics, epigenetics, and molecular features, there is a growing appreciation for the heterogeneity of hepatoblastoma and the likelihood that treatment strategies can be better individualized to improve outcomes in high-risk patients. This progress is expected to accelerate further when results from the results from the Pediatric Hepatic International Tumor Trial (PHITT) are published. These data are expected to be available in 2025, and may help with prognostication and understanding the biology of hepatoblastoma in relation to outcomes.

Treatment Strategies in Hepatoblastoma
For low-grade hepatoblastoma, the first-line therapy is surgery, which can be sufficient for cure without relapse in selected patients with PRETEXT group 1 disease. Although only 40% to 60% of patients have resectable disease at diagnosis,¹⁰ there are several strategies to shrink tumor bulk, particularly chemotherapy due to the relatively high sensitivity of hepatoblastoma to cytotoxic therapies. The intensity of chemotherapy is increased relative to risk.¹¹ For example, cisplatin-based regimens are considered for low-risk patients, while additional therapies, such as doxorubicin, irinotecan, or both, are added in patients at higher risk. Cure is common if these regimens permit a margin-free resection, although relapse does occur in a subset of patients.

If adequate debulking of the tumor cannot be achieved with conventional surgery, liver transplantation is typically offered for patients without extrahepatic disease or after distant metastases have been successfully excised. With liver transplantation and combination therapies to inhibit relapse associated with seeding, long-term survival rates of 80% have been reported.³ Judicious use of transplantation in patients with high-risk disease that raises the potential for relapse has been credited with rates of long-term survival that exceed 80% in some series. However, there is concern of offering transplantation when it is not necessary. In patients who are high risk with multiple lesions in the liver, there is a general agreement that transplantation reduces the likelihood of subsequent relapse; however, as the precision of aggressive resection coupled with effective chemotherapy has improved, there are more patients in whom the optimal choice might not be debated by experts.

Review articles typically cite the likelihood of an overall 5-year survival in patients with hepatoblastoma as being on the order of 80%.¹ This rate includes children with late-onset disease, which is generally associated with a worse prognosis, and patients who eventually experience disease relapse. Survival rates are now likely to be substantially higher, with progress developing better treatment protocols for both groups. In the absence of high-risk features, long-term survival rates of 90% or higher are now being reported in some centers with high relative volumes of hepatoblastoma, regardless of baseline risks. 

PHITT
The rarity of hepatoblastoma poses a significant challenge to conducting prospective studies with sufficient sample sizes to evaluate the overall efficacy of treatments and their effectiveness in patient subgroups based on specific clinical characteristics and disease severity. PHITT is the first international collaborative liver tumors trial to use a consensus approach. Centers in Europe, Japan, and the United States are participating through regional cancer study consortia. The Cincinnati Children’s Hospital and Medical Center, a leader in hepatoblastoma management in the United States, is anchoring this effort for the Children’s Oncology Group. 

In addition to assessing treatment strategies in larger patient cohorts, PHITT is expanding the data available to correlate outcomes across different stages and risk categories based on histological and biological classifications. Hepatoblastoma and hepatocellular carcinoma are being addressed in PHITT, but the design schema for these malignancies differs. For patients enrolled with hepatoblastoma, 4 risk groups have been defined, ranging from very low to high. Within these risk categories, flow charts provide guide selection of treatments based on clinical and disease features.

Cincinnati Children’s Hospital and Medical Center is one of the most active centers for the treatment of hepatoblastoma in the Unites States but manages only 15 to 20 cases of this rare disease per year. PHITT is expected to play a critical role in achieving a high level of valuable data, and the first sets of outcomes from this collaboration are anticipated to be available in early 2025. As the study progresses, meaningful data are expected for the most challenging and some of the rarest hepatoblastoma risk groups.

Summary
The rates of cure are now approaching 100% with surgery and chemotherapy in patients with localized or locally advanced hepatoblastoma. For more advanced, unresectable disease, liver transplantation is effective in most patients, providing high rates of long-term survival. For patients with relapsed disease, advanced treatment protocols at centers with high relative volumes
of hepatoblastoma are now regularly achieving a second remission—many of which are durable. Although prognosis is less favorable in patients who experience a second relapse, long-term survival is achieved even in a proportion of these children. Substantial rates of response and long-term survival have been common in hepatoblastoma diagnosed at early stages, but the recent progress in advanced hepatoblastoma is credited to more aggressive therapies based on a better understanding of the disease characteristics that allows for individualized therapy. There is hope that the larger pool of data becoming available in 2025 from PHITT will prove to be an additional source of information that guides further advances in managing this rare disease.

Read more from the 2024 Rare Diseases Report: Hematology and Oncology.

Introduction
Hepatoblastoma accounts for most pediatric liver cancers, but accounts for only 1% of all malignancies in children. Rates of hepatoblastoma have increased gradually over the past 20 years for unclear reasons, but it remains a rare malignancy. In the 1970s, only a small percentage of patients survived long-term. Today, 5-year survival rates range from 65% to over 90%, depending on risk factors, thanks to recent advancements in the understanding and treatment of hepatoblastoma.^1-5 Improved risk stratification has led to better staging and more personalized treatment approaches. To further improve survival, current research is concentrated on improving outcomes in the most challenging patient subsets, such as those with metastatic disease and patients with disease relapse.

Background
Hepatoblastoma is typically diagnosed in the first 2 years of life.⁶ Accounting for more than 60% of pediatric hepatic malignancies worldwide, the incidence of hepatoblastoma is increasing. Results from a study evaluating the incidence between 2001 and 2017 showed a 2% annual increase documented in children aged from birth to 4 years in the United States, climbing to 5.8% annually among children aged 5 to 9 years.² Risk factors for hepatoblastoma include maternal preeclampsia, premature birth, and parental smoking.⁷ The degree to which each of these factors plays a role is uncertain. A genetic etiology is suspected in a minority of hepatoblastoma cases, but it is associated with several genetic diseases, including Beckwith-Weidemann syndrome, familial adenomatous polyposis, and Prader-Willi syndrome.⁸ Genetic mutations in the Wnt signaling pathway that result in the accumulation of beta-catenin have also been found in sporadic, nonfamilial cases.⁹

Although this condition generally presents as a single abdominal mass in the right lobe of the liver, multifocal hepatoblastoma at diagnosis does occur.¹⁰ In most patients, alpha-fetoprotein (AFP) is significantly elevated.¹¹ An estimated 20% of patients present with metastases, which are most commonly found in the lung.¹² While ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI) can be used to define the extent of the tumor in the liver, a chest CT is appropriate to look for metastases beyond the liver.¹³

Of the 2 broad histological categories commonly used to characterize hepatoblastoma, the more common epithelial form consists of fetal or embryonal liver cells. The mixed epithelial-mesenchymal form that accounts for 20% to 30% of hepatoblastomas features epithelial and primitive mesenchymal tissue, often with osteoid tissue or cartilage⁶; both have numerous histological subtypes. For example, the epithelial type can be further characterized by a well- or poorly-differentiated appearance, while the mixed type can be subdivided by the presence or absence of teratoid features.

Prior to 2017, there was considerable disparity in the way hepatoblastomas were characterized and staged among the major research consortiums. This issue was addressed when a consortium was established in which pediatric oncology groups pooled their data. The Children’s Hepatic tumors International Collaboration (CHIC) released the PRETEXT (PRETreatment EXTent of disease) approach.^7,14 Based on comprehensive data from 1605 children participating in multicenter trials, the CHIC risk stratification defines and provides risk trees for very low-, low-, intermediate-, and high-risk groups. The most important predictors included AFP levels, patient age, extent of disease in the liver (particularly involving major hepatic veins), and the presence of metastases.

Further improvements to the diagnosis and staging of hepatoblastoma are credited to consensus-based recommendations for imaging that were created in the context of the PRETEXT staging system.¹³ While ultrasound is recommended for the initial approach to diagnosis, this consensus calls for MRI with hepatobiliary contrast to better characterize the lesion and detect satellite lesions. This form of imaging is also recommended for follow-up after treatment, but results should be interpreted in the context of biomarkers, such as AFP levels, pathologic grading, and tumor subtypes.

In patients with the most common familial disorders associated with a predisposition for hepatoblastoma, such as adenomatous polyposis, Beckwith-Weidemann spectrum, or trisomy 18, regular surveillance for hepatoblastoma is recommended during the early years of life.⁸ Characterization of the genetic and molecular features of patients who present with hepatoblastoma might be useful in determining prognosis. Of genetic features, mutations in the CTNNB1 gene are the most common, but several genes in the Wnt pathway are also linked to hepatoblastoma formation.⁹

Along with the progress in subtyping patients by genetics, epigenetics, and molecular features, there is a growing appreciation for the heterogeneity of hepatoblastoma and the likelihood that treatment strategies can be better individualized to improve outcomes in high-risk patients. This progress is expected to accelerate further when results from the results from the Pediatric Hepatic International Tumor Trial (PHITT) are published. These data are expected to be available in 2025, and may help with prognostication and understanding the biology of hepatoblastoma in relation to outcomes.

Treatment Strategies in Hepatoblastoma
For low-grade hepatoblastoma, the first-line therapy is surgery, which can be sufficient for cure without relapse in selected patients with PRETEXT group 1 disease. Although only 40% to 60% of patients have resectable disease at diagnosis,¹⁰ there are several strategies to shrink tumor bulk, particularly chemotherapy due to the relatively high sensitivity of hepatoblastoma to cytotoxic therapies. The intensity of chemotherapy is increased relative to risk.¹¹ For example, cisplatin-based regimens are considered for low-risk patients, while additional therapies, such as doxorubicin, irinotecan, or both, are added in patients at higher risk. Cure is common if these regimens permit a margin-free resection, although relapse does occur in a subset of patients.

If adequate debulking of the tumor cannot be achieved with conventional surgery, liver transplantation is typically offered for patients without extrahepatic disease or after distant metastases have been successfully excised. With liver transplantation and combination therapies to inhibit relapse associated with seeding, long-term survival rates of 80% have been reported.³ Judicious use of transplantation in patients with high-risk disease that raises the potential for relapse has been credited with rates of long-term survival that exceed 80% in some series. However, there is concern of offering transplantation when it is not necessary. In patients who are high risk with multiple lesions in the liver, there is a general agreement that transplantation reduces the likelihood of subsequent relapse; however, as the precision of aggressive resection coupled with effective chemotherapy has improved, there are more patients in whom the optimal choice might not be debated by experts.

Review articles typically cite the likelihood of an overall 5-year survival in patients with hepatoblastoma as being on the order of 80%.¹ This rate includes children with late-onset disease, which is generally associated with a worse prognosis, and patients who eventually experience disease relapse. Survival rates are now likely to be substantially higher, with progress developing better treatment protocols for both groups. In the absence of high-risk features, long-term survival rates of 90% or higher are now being reported in some centers with high relative volumes of hepatoblastoma, regardless of baseline risks. 

PHITT
The rarity of hepatoblastoma poses a significant challenge to conducting prospective studies with sufficient sample sizes to evaluate the overall efficacy of treatments and their effectiveness in patient subgroups based on specific clinical characteristics and disease severity. PHITT is the first international collaborative liver tumors trial to use a consensus approach. Centers in Europe, Japan, and the United States are participating through regional cancer study consortia. The Cincinnati Children’s Hospital and Medical Center, a leader in hepatoblastoma management in the United States, is anchoring this effort for the Children’s Oncology Group. 

In addition to assessing treatment strategies in larger patient cohorts, PHITT is expanding the data available to correlate outcomes across different stages and risk categories based on histological and biological classifications. Hepatoblastoma and hepatocellular carcinoma are being addressed in PHITT, but the design schema for these malignancies differs. For patients enrolled with hepatoblastoma, 4 risk groups have been defined, ranging from very low to high. Within these risk categories, flow charts provide guide selection of treatments based on clinical and disease features.

Cincinnati Children’s Hospital and Medical Center is one of the most active centers for the treatment of hepatoblastoma in the Unites States but manages only 15 to 20 cases of this rare disease per year. PHITT is expected to play a critical role in achieving a high level of valuable data, and the first sets of outcomes from this collaboration are anticipated to be available in early 2025. As the study progresses, meaningful data are expected for the most challenging and some of the rarest hepatoblastoma risk groups.

Summary
The rates of cure are now approaching 100% with surgery and chemotherapy in patients with localized or locally advanced hepatoblastoma. For more advanced, unresectable disease, liver transplantation is effective in most patients, providing high rates of long-term survival. For patients with relapsed disease, advanced treatment protocols at centers with high relative volumes
of hepatoblastoma are now regularly achieving a second remission—many of which are durable. Although prognosis is less favorable in patients who experience a second relapse, long-term survival is achieved even in a proportion of these children. Substantial rates of response and long-term survival have been common in hepatoblastoma diagnosed at early stages, but the recent progress in advanced hepatoblastoma is credited to more aggressive therapies based on a better understanding of the disease characteristics that allows for individualized therapy. There is hope that the larger pool of data becoming available in 2025 from PHITT will prove to be an additional source of information that guides further advances in managing this rare disease.

Read more from the 2024 Rare Diseases Report: Hematology and Oncology.