What is the initial treatment approach for children diagnosed with hepatoblastoma (hepatic tumors)?

Initial Treatment Approach for Pediatoblastoma in Children

The gold standard treatment for hepatoblastoma is perioperative cisplatin-based chemotherapy followed by complete surgical resection of all viable tumor. 1

Immediate Risk Stratification and Referral

All children with hepatoblastoma should undergo PRETEXT (Pretreatment Extent of Disease) staging at diagnosis to determine resectability and guide early referral decisions. 1

• Children with nonmetastatic but otherwise unresectable hepatoblastoma must be referred for liver transplant evaluation at diagnosis or no later than after 2 rounds of chemotherapy. 1
• High-risk features requiring early transplant center referral include: PRETEXT IV disease (all four liver sections involved), complex PRETEXT III disease (multifocal or venous thrombosis), or centrally located tumors unlikely to achieve tumor-free margins. 1

Initial Chemotherapy Protocol

The Children's Oncology Group protocol (COG-AHEP0731) recommends initiating cisplatin-based chemotherapy immediately after diagnosis, with tumor resectability assessed after 2-4 cycles. 1

Standard-Risk Disease (Resectable at Diagnosis)

• For completely resected stage I-II hepatoblastoma, only 2 cycles of cisplatin (100 mg/m²), fluorouracil (600 mg/m²), and vincristine are required postoperatively. 2
• This minimal adjuvant approach achieves 88% 5-year event-free survival while reducing ototoxicity exposure. 2

Intermediate-Risk Disease (Potentially Resectable)

• Administer 2-4 cycles of cisplatin-based chemotherapy (typically cisplatin 100 mg/m², doxorubicin 60 mg/m², ifosfamide 3 g/m²) before reassessing resectability. 1, 3
• Approximately 50-60% of initially unresectable tumors become resectable after neoadjuvant chemotherapy. 3

High-Risk Disease (Unresectable/Metastatic)

• For tumors unresponsive to standard cisplatin-based regimens, consider carboplatin (800 mg/m²) and etoposide (400 mg/m²) with potential escalation to high-dose therapy. 3
• This approach achieves tumor response in 50-60% of high-risk cases. 3

Surgical Decision Algorithm After Chemotherapy

After 2-4 cycles of chemotherapy, reassess tumor extent and proceed according to this hierarchy: 1

1. If complete resection with negative margins is achievable → perform conventional hepatic resection 1
2. If tumor remains unresectable but confined to liver → proceed to primary liver transplantation 1
3. If aggressive resection would leave positive margins or insufficient liver remnant → proceed directly to transplantation rather than attempting marginal resection 4

Management of Metastatic Disease

Children with pulmonary metastases at diagnosis can still be considered for curative treatment if specific criteria are met after chemotherapy: 1

• Proceed with liver transplantation if either:
  • Pulmonary metastases are no longer visible on CT after chemotherapy, OR 1
  • Residual pulmonary nodules are completely resected with tumor-free margins confirmed on pathology 1

Critical Survival Data Informing Treatment Decisions

Primary liver transplantation for unresectable hepatoblastoma achieves 82% 10-year survival, while "rescue" transplantation after failed resection achieves only 30% 10-year survival. 1

This dramatic survival difference underscores the importance of:

• Early transplant center involvement for borderline resectable cases 1
• Avoiding marginal resections that may compromise future transplant candidacy 4
• Proceeding directly to transplantation when complete resection is unlikely 1

Common Pitfalls to Avoid

Do not delay transplant referral beyond 2 chemotherapy cycles for clearly unresectable disease - the survival advantage of primary transplantation over rescue transplantation is substantial (82% vs 30% at 10 years). 1

Do not attempt aggressive conventional resection with anticipated positive margins - this converts a primary transplant candidate (82% survival) into a rescue transplant candidate (30% survival). 1

Do not exclude patients with pulmonary metastases from curative intent - if metastases resolve or are completely resectable after chemotherapy, transplant outcomes are equivalent to non-metastatic disease. 1

Do not use adult HCC criteria (Milan criteria) for hepatoblastoma - children with hepatoblastoma can achieve excellent outcomes with much larger tumors than would be acceptable for HCC, as hepatoblastoma has better biology and chemosensitivity. 1