# Hepatoblastoma

Source: https://onco.cc/cancers/hepatoblastoma/  
OnCo record `hepatoblastoma` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Hepatoblastoma is a childhood liver cancer, mostly of toddlers, cured in most standard-risk cases with cisplatin chemotherapy and surgery, including liver transplant when the tumour cannot be cut out. Sodium thiosulfate given after cisplatin halves the permanent hearing loss cisplatin causes, and became the first approved otoprotectant in 2022.

## Summary

Hepatoblastoma is an embryonal liver tumour with CTNNB1 (β-catenin) mutations in most cases, associated with prematurity, Beckwith-Wiedemann syndrome and familial adenomatous polyposis. Alpha-fetoprotein (AFP) is elevated in >90% and tracks response; very low AFP (<100 ng/mL) marks an aggressive small-cell-undifferentiated variant. Staging uses PRETEXT (extent within the liver) plus annotation factors (vascular involvement, extrahepatic extension, metastases, rupture) under the international CHIC risk stratification.

Treatment combines cisplatin-based chemotherapy with complete surgical resection; standard-risk disease is cured in ~90% with cisplatin monotherapy (SIOPEL-3), high-risk disease uses cisplatin-doxorubicin (PLADO) or dose-dense cisplatin (SIOPEL-4), and unresectable tumours confined to the liver are transplanted with excellent outcomes. The Paediatric Hepatic International Tumour Trial (PHITT) harmonises COG, SIOPEL and JPLT approaches. Sodium thiosulfate given 6 hours after cisplatin halves permanent hearing loss without compromising survival (SIOPEL-6, NEJM 2018), leading to FDA approval of the first otoprotectant (2022).

## Fields

- Kind: Cancer
- Last checked: 2026-09-08
- Tags: gap-fill; paediatric
- Group: paediatric
- Burden: Hepatoblastoma is the most common childhood liver cancer (~1-2 per million children per year, ~100-150 cases per year in the US), mostly under age 3; incidence rising with survival of very-low-birth-weight infants.
- Subtypes: Epithelial: fetal (well-differentiated, favourable), embryonal, macrotrabecular; Small-cell undifferentiated (low AFP, aggressive; exclude rhabdoid/INI1 loss); Mixed epithelial-mesenchymal (with or without teratoid features); Hepatocellular neoplasm NOS / transitional liver cell tumour (older children)
- Biomarkers: Serum AFP (diagnosis, response, relapse; <100 ng/mL poor); PRETEXT / POST-TEXT group and annotation factors (V, P, E, M, R); CHIC risk group (age, AFP, PRETEXT, metastases); CTNNB1 mutation, NFE2L2, TERT; Germline APC (FAP) and 11p15 (Beckwith-Wiedemann)

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/hepatoblastoma/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/hepatoblastoma/#overview [4 state-of-the-art points]
- What it is (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/hepatoblastoma/#what-it-is [4 subtypes]
- Finding it (on the hub): How it shows itself, how it is confirmed, what screening exists, and the biomarkers clinicians test for. https://onco.cc/cancers/hepatoblastoma/#finding-it [5 biomarkers]
- Treating it (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/hepatoblastoma/#treating-it [4 settings, 3 decisions with options]
- Evidence (on the hub): Trials recruiting now, the landmark trials, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/hepatoblastoma/#evidence [3 trials, 3 key papers, 7 milestones]
- The science (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/hepatoblastoma/#science [1 pathway]
- Where you are (own page): Cases by country, the UK and NHS pathway and other country lenses, and the expert centres with trials on record. https://onco.cc/cancers/hepatoblastoma/where-you-are/
- Living with it (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/hepatoblastoma/#living-with-it [18 questions, 6 red cards]
- What is coming (own page): Everything in development, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/hepatoblastoma/coming/ [6 medicines, 3 trials, 4 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/hepatoblastoma/data/ [33 connected records]

## Standard of care

- Very low / standard risk (PRETEXT I-III, resectable, AFP >100): Upfront resection for PRETEXT I-II (COG) or cisplatin monotherapy ×4-6 with delayed resection (SIOPEL-3); sodium thiosulfate after each cisplatin dose for otoprotection. ([Cisplatin](https://onco.cc/drugs/cisplatin/), [Sodium thiosulfate (otoprotectant)](https://onco.cc/drugs/sodium-thiosulfate/), [SIOPEL-3](https://onco.cc/trials/siopel-3/))
- High risk (metastatic, AFP <100, PRETEXT IV, vascular involvement): Cisplatin-doxorubicin (PLADO) or dose-dense cisplatin (SIOPEL-4), resection of primary and lung metastases; consider C5VD (COG). ([Cisplatin](https://onco.cc/drugs/cisplatin/), [Doxorubicin](https://onco.cc/drugs/doxorubicin/), [Vincristine](https://onco.cc/drugs/vincristine/), [Fluorouracil (5-FU)](https://onco.cc/drugs/fluorouracil/), [SIOPEL-4](https://onco.cc/trials/siopel-4/))
- Unresectable after chemotherapy (POST-TEXT IV, central vascular involvement): Orthotopic liver transplantation (5-year survival ~80%); early referral to a transplant centre. ([Liver transplantation for cancer (Milan criteria and beyond)](https://onco.cc/technologies/liver-transplant-oncology/))
- Relapsed/refractory: Irinotecan-based salvage, surgery for isolated recurrence, transplant if liver-confined; trials. ([Irinotecan (and liposomal irinotecan)](https://onco.cc/drugs/irinotecan/), [Liver transplantation for cancer (Milan criteria and beyond)](https://onco.cc/technologies/liver-transplant-oncology/))

## State of the art

- Overall survival ~80-90%; cisplatin alone cures most standard-risk children, and transplant rescues unresectable disease.
- Sodium thiosulfate is a model of supportive-care evidence: a randomised trial in children changed a global standard and produced a drug approval.
- PHITT is the first global paediatric liver tumour trial with harmonised risk groups.
- Low-AFP small-cell undifferentiated tumours and metastatic disease remain the challenging minority.

## Open problems

- Metastatic and low-AFP disease.
- Long-term effects of cisplatin (hearing, kidney) and doxorubicin (heart).
- Rising incidence with extreme prematurity.
- Transplant organ availability and lifelong immunosuppression in children.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Hepatoblastoma
- NCI PDQ: childhood liver cancer: https://www.cancer.gov/types/liver/patient/child-liver-treatment-pdq
- SIOPEL-6 (NEJM 2018): https://doi.org/10.1056/NEJMoa1801109
- PHITT trial: https://clinicaltrials.gov/study/NCT03017326

## Connected records

- cancers: [Childhood cancers (all types)](https://onco.cc/cancers/childhood-cancers/), [Childhood lung and airway tumours (pleuropulmonary blastoma, tracheobronchial tumours)](https://onco.cc/cancers/pleuropulmonary-blastoma/), [Germ cell tumours of childhood and adolescence (extracranial and CNS)](https://onco.cc/cancers/paediatric-germ-cell-tumours/), [Neuroblastoma (paediatric)](https://onco.cc/cancers/neuroblastoma/), [Pancreatoblastoma](https://onco.cc/cancers/pancreatoblastoma/), [Rare cancers of childhood (NCI PDQ umbrella)](https://onco.cc/cancers/rare-childhood-cancers/), [Retinoblastoma](https://onco.cc/cancers/retinoblastoma/), [Wilms tumour (nephroblastoma)](https://onco.cc/cancers/wilms-tumor/)
- technologies: [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [HCC surveillance in cirrhosis (ultrasound + AFP)](https://onco.cc/technologies/hcc-surveillance/), [Liver transplantation for cancer (Milan criteria and beyond)](https://onco.cc/technologies/liver-transplant-oncology/), [Platinum agents](https://onco.cc/technologies/platinum/), [Survivorship care and late-effects surveillance](https://onco.cc/technologies/survivorship-care-plan/), [Ultrasound](https://onco.cc/technologies/ultrasound/)
- drugs: [Cisplatin](https://onco.cc/drugs/cisplatin/), [Doxorubicin](https://onco.cc/drugs/doxorubicin/), [Fluorouracil (5-FU)](https://onco.cc/drugs/fluorouracil/), [Irinotecan (and liposomal irinotecan)](https://onco.cc/drugs/irinotecan/), [Sodium thiosulfate (otoprotectant)](https://onco.cc/drugs/sodium-thiosulfate/), [Vincristine](https://onco.cc/drugs/vincristine/)
- companies: [Children's Oncology Group (COG)](https://onco.cc/companies/childrens-oncology-group/), [Eureka Therapeutics](https://onco.cc/companies/eureka-therapeutics/)
- pathways: [Wnt / β-catenin](https://onco.cc/pathways/wnt/)
- terms: [Alpha-fetoprotein (AFP)](https://onco.cc/terms/afp/), [PRETEXT and CHIC risk groups (hepatoblastoma)](https://onco.cc/terms/pretext-chic/)
- key papers: [SIOPEL-3: cisplatin versus cisplatin plus doxorubicin for standard-risk hepatoblastoma](https://onco.cc/key-papers/paper-siopel-3-cisplatin-vs-plado-standard-risk-hepatoblastoma-perilongo-nejm-2009/), [SIOPEL-4: dose-dense cisplatin-based chemotherapy and surgery for high-risk hepatoblastoma](https://onco.cc/key-papers/paper-siopel-4-dose-dense-cisplatin-high-risk-hepatoblastoma-zsiros-lancet-oncol-2013/), [Sodium Thiosulfate for Protection from Cisplatin-Induced Hearing Loss](https://onco.cc/key-papers/paper-brock-n-engl-j-med/)
- trials: [ET140203 T Cells in Pediatric Subjects With Hepatoblastoma, HCN-NOS, or Hepatocellular Carcinoma](https://onco.cc/trials/nct04634357/), [SIOPEL-3](https://onco.cc/trials/siopel-3/), [SIOPEL-4](https://onco.cc/trials/siopel-4/)
- collections: [Alex's Lemonade Stand Foundation (ALSF)](https://onco.cc/collections/alexs-lemonade-stand/)

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JSON: https://onco.cc/api/v1/entities/hepatoblastoma.json