Outcomes of children with well-differentiated fetal hepatoblastoma treated with surgery only: Report from Children's Oncology Group Trial, AHEP0731


      • Pure or well differentiated fetal histology has the best outcomes out of all hepatoblastoma histologies.
      • Well differentiated fetal tumor surgically removed at diagnosis are curable without adjuvant chemotherapy.
      • HB completely resected at diagnosis with 100% well differentiated fetal histology is curable with surgery and no adjuvant chemotherapy.
      • Evidence-based surgical guidelines utilizing internationally constructed criteria are crucial for identifying appropriate patients for resection at diagnosis.



      Hepatoblastoma (HB) requires surgical resection for cure, but only 20–30% of patients have resectable disease at diagnosis. Patients who undergo partial hepatectomy at diagnosis have historically received 4–6 cycles of adjuvant chemotherapy; however, those with 100% well-differentiated fetal histology (WDF) have been observed to have excellent outcomes when treated with surgery alone.

      Patients and methods

      Patients on the Children's Oncology Group non randomized, multicenter phase III study, AHEP0731, were stratified based on Evan's stage, tumor histology, and serum alpha-fetoprotein level at diagnosis. Patients were eligible for the very low risk stratum of surgery and observation if they had a complete resection at diagnosis and rapid central histologic review demonstrated HB with 100% WDF histology.


      A total of 8 eligible patients were enrolled on study between September 14, 2009 and May 28, 2014. Outcome current to 06/30/2020 was used in this analysis. The median age at enrollment was 22.5 months (range: 8–84 months) and the median AFP at enrollment was 714 ng/ml (range: 18–77,747 ng/mL). With a median follow-up of 6.6 years (range: 3.6–9.8 years), the 5-year event-free (EFS) and overall survival (OS) were both 100%.


      This report supports that HB with 100% WDF histology completely resected at diagnosis is curable with surgery only. The development of evidence-based surgical guidelines utilizing criteria based on PRETEXT group, vascular involvement (annotation factors), tumor-specific histology and corresponding biology will be crucial for optimizing which patients are candidates for resection at diagnosis followed by observation.

      Level of evidence

      Prognosis study, Level I evidence.



      HB (hepatoblastoma), PFH (pure fetal histology), COG (Children's oncology group), WDF (well-differentiated fetal histology), PRETEXT (pretreatment extent of disease), AFP (alpha fetoprotein), V (vena cava hepatic veins), P (portal veins), E (extrahepatic disease), F (multifocal disease), R (rupture at diagnosis), C (caudate lobe involvement), N (lymph node involvement), and M (metastatic disease), CR (complete response), EFS (event-free survival), OS (overall survival)
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