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Cancer Health Center

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Childhood Liver Cancer Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Treatment of Hepatoblastoma


Treatment Options for Stage IV

The outcome for metastatic hepatoblastoma at diagnosis is poor, but long-term survival and cure is possible.[3,6,7] Survival rates at 3 to 5 years range from 20% to 60%.[19,20,21]

  • Chemotherapy followed by reassessment of surgical resectability. If possible, this is followed by surgical resection of primary tumor and extrahepatic disease. Additional chemotherapy will follow if the primary tumor was completely resected.

    The standard regimen is four courses of cisplatin/vincristine/fluorouracil [6] or doxorubicin/cisplatin combination chemotherapy [5,19] followed by attempted complete tumor resection. If the tumor is completely removed, two postoperative courses of the same chemotherapy should be given.

    In a study employing a well-tolerated regimen of doxorubicin/cisplatin chemotherapy, about 50% of patients with metastases at presentation survived 5 years from diagnosis. Half of these survivors had developed progressive disease that was successfully treated with surgery and other interventions.[5] In another study, platinum- and doxorubicin-based multidrug chemotherapy induced complete regression in approximately 50% of patients, with subsequent 3-year EFS of 56%.[20] A prospective feasibility trial of dose-dense, cisplatin-based chemotherapy and radical surgery in 62 patients with high-risk hepatoblastoma (SIOPEL-4 [NCT00077389]) resulted in a 3-year EFS of 76% and 3-year OS of 83%.[22][Level of evidence: 3iiDi] In this study, of 37 patients with distant metastases, 27 (78%) were surviving disease free at 3 years.[22]

    Several studies have tested different chemotherapy regimens. A randomized clinical trial compared cisplatin/vincristine/fluorouracil with cisplatin/doxorubicin. Although outcome was nominally higher for children receiving cisplatin/doxorubicin, this difference was not statistically significant, and the combination of cisplatin/vincristine/fluorouracil was less toxic than the regimen of cisplatin/doxorubicin.[6] The cisplatin/doxorubicin used in the international studies appears to be less toxic than that in the North American study.[5] Addition of carboplatin to intensify the cisplatin/doxorubicin may have reduced its efficacy.[4] A regimen of intensified platinum therapy with alternating cisplatin and carboplatin was associated with a decrease in EFS.[10] A combination of ifosfamide, cisplatin, and doxorubicin has also been successfully used in the treatment of advanced-stage disease.[9]

    If possible, stage IV patients with resected primary tumor should have remaining pulmonary metastases surgically removed.[19] A review of patients treated on a U.S. Intergroup trial suggested that resection may be done at the time of resection of the primary tumor.[21][Level of evidence: 3iiA]

  • Chemotherapy followed by reassessment of surgical resectability. If extrahepatic disease is in complete remission and the primary tumor remains unresectable, an orthotopic liver transplantation may be performed. There are discrepant results on the outcomes for patients with lung metastases at diagnosis who undergo orthotopic liver transplantation following complete resolution of lung disease in response to pretransplant chemotherapy. Some studies have reported favorable outcomes for this group of patients,[9] while others have noted high rates of hepatoblastoma recurrence.[11,12,15,17] All of these studies are limited by small patient numbers; further study is needed to better define outcomes for this subset of patients.
  • Chemotherapy followed by reassessment of surgical resectability. If extrahepatic disease is not resectable (post neoadjuvant chemotherapy), alternative treatment approaches may include the following:

    Patients whose extrahepatic tumors remain unresectable or who are not transplant candidates should be considered for alternative chemotherapy such as irinotecan,[23,24,25]; [26][Level of evidence: 3iiA] high-dose cisplatin/etoposide, continuous-infusion doxorubicin, radiation therapy,[3,27] or chemoembolization by hepatic arterial infusion.[18,28]

  • Chemotherapy followed by radiation therapy followed by surgical re-exploration for patients in whom extrahepatic disease is controlled, but the primary tumor remains unresectable following treatment with standard chemotherapy regimens.
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