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Childhood Liver Cancer Treatment (PDQ®)

  • Last Modified: 05/05/2014

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Treatment of Hepatocellular Carcinoma

Treatment Options for Stages I and II
Treatment Options for Stage III
Treatment Options for Presurgically Staged (PRETEXT) Stage 4
Treatment Options for Postsurgically Staged Stage IV



Treatment Options for Stages I and II
  • Complete surgical resection of primary tumor followed by chemotherapy.

    In a randomized trial, seven of eight patients with stage I hepatocellular carcinoma survived disease free after adjuvant cisplatin-based chemotherapy.[1] In a survey of childhood liver tumors treated prior to the consistent use of chemotherapy, only 12 of 33 patients with hepatocellular carcinoma who had complete excision of the tumor survived.[2] This suggests that adjuvant chemotherapy may benefit children with completely resected hepatocellular carcinoma. Treatment with cisplatin and doxorubicin may be recommended as adjuvant therapy since these are active agents in the treatment of hepatocellular carcinoma.[3] Despite improvements in surgical techniques, chemotherapy delivery, and patient supportive care in the past 20 years, clinical trials of cancer chemotherapy for hepatocellular carcinoma have not shown improved outcome.[3]

  • Chemotherapy followed by complete surgical resection of primary tumor.[3]
  • An alternative treatment approach might be transarterial chemoembolization followed by complete surgical resection of primary tumor.

    Studies in adults in China suggest that repeated hepatic transarterial chemoembolization before surgery may improve the outcome of subsequent hepatectomy.[4] (Refer to the PDQ summary on Adult Primary Liver Cancer Treatment for more information.)

Treatment Options for Stage III
  • Chemotherapy followed by reassessment of surgical resectability followed by complete surgical resection of primary tumor.

    The use of neoadjuvant chemotherapy followed by complete gross surgical resection of the primary tumor is necessary for cure.

  • Chemotherapy followed by reassessment of surgical resectability. If the primary tumor remains unresectable, an orthotopic liver transplantation may be performed.

    Liver transplantation has been a successful therapy for children with unresectable hepatocellular carcinoma; survival is about 60% with most deaths resulting from tumor recurrence.[5-8]

  • Chemotherapy followed by reassessment of surgical resectability. If the primary tumor remains unresectable, alternative treatment approaches may include the following:
    • Cryosurgery.
    • Intratumoral injection of alcohol.
    • Transarterial chemoembolization.
    • Radiation therapy.

    No specific treatment has proven effective for unresectable hepatocellular carcinoma in the pediatric age group. A prospective study of 41 patients who were to receive preoperative cisplatin/doxorubicin chemotherapy resulted in some degree of decrease in tumor size with a decrease in alpha-fetoprotein (AFP) levels in about 50% of patients. The responders had a superior tumor resectability and survival, although the overall survival (OS) was 28% and only those undergoing complete resection survived.[3] Cryosurgery, intratumoral injection of alcohol, and radiofrequency ablation can successfully treat small (<5 cm) tumors in adults with cirrhotic livers.[4,9,10] Some local approaches such as cryosurgery, radiofrequency ablation, and transarterial chemoembolization that suppress hepatocellular carcinoma tumor progression are used as bridging therapy in adults to delay tumor growth while on a waiting list for cadaveric liver transplant.[11] Transarterial chemoembolization has been used in a few children to successfully shrink tumor size to permit resection.[4,12] (Refer to the PDQ summary on Adult Primary Liver Cancer Treatment for more information.)

Treatment Options for Presurgically Staged (PRETEXT) Stage 4
  • Chemotherapy followed by reassessment of surgical resectability followed by complete surgical resection of primary tumor.

    The use of neoadjuvant chemotherapy followed by complete gross surgical resection of the primary tumor is necessary for cure.

  • Chemotherapy followed by reassessment of surgical resectability. If the primary tumor remains unresectable, an orthotopic liver transplantation may be performed.

    Liver transplantation has been successful therapy for children with unresectable hepatocellular carcinoma; survival is about 60% with most deaths resulting from tumor recurrence.[5-7]

  • Chemotherapy followed by reassessment of surgical resectability. If the primary tumor remains unresectable, alternative treatment approaches may include the following:
    • Cryosurgery.
    • Intratumoral injection of alcohol.
    • Transarterial chemoembolization.
    • Radiation therapy.

    No specific treatment has proven effective for unresectable hepatocellular carcinoma in the pediatric age group. A prospective study of 41 patients who were to receive preoperative cisplatin/doxorubicin chemotherapy resulted in some degree of decrease in tumor size with a decrease in AFP level in about 50% of patients. The responders had a superior tumor resectability and survival, although the OS was 28% and only those undergoing complete resection survived.[3] The 5-year OS for PRETEXT stage 4 patients, including those with metastasis and/or extrahepatic disease, was 1 in 13.[3] Cryosurgery, intratumoral injection of alcohol, and radiofrequency ablation can successfully treat small (<5 cm) tumors in adults with cirrhotic livers.[4,9,10] Some local approaches such as cryosurgery, radiofrequency ablation, and transarterial chemoembolization that suppress hepatocellular carcinoma tumor progression are used as bridging therapy in adults to delay tumor growth while on a waiting list for cadaveric liver transplant.[6,11,13] Transarterial chemoembolization has been used in a few children to successfully shrink tumor size to permit resection.[4,12] (Refer to the PDQ summary on Adult Primary Liver Cancer Treatment for more information.)

Treatment Options for Postsurgically Staged Stage IV

No particular treatment has proven effective for metastatic hepatocellular carcinoma in the pediatric age group. In two prospective trials, cisplatin plus either vincristine/fluorouracil or continuous infusion doxorubicin was ineffective in adequately treating 25 patients with metastatic hepatocellular carcinoma.[1,3] Occasional patients may benefit from treatment with cisplatin/doxorubicin therapy, especially if localized hepatic tumor shrinks adequately to allow resection of disease. (Refer to the PDQ summary on Adult Primary Liver Cancer Treatment for more information.)

References
  1. Katzenstein HM, Krailo MD, Malogolowkin MH, et al.: Hepatocellular carcinoma in children and adolescents: results from the Pediatric Oncology Group and the Children's Cancer Group intergroup study. J Clin Oncol 20 (12): 2789-97, 2002.  [PUBMED Abstract]

  2. Exelby PR, Filler RM, Grosfeld JL: Liver tumors in children in the particular reference to hepatoblastoma and hepatocellular carcinoma: American Academy of Pediatrics Surgical Section Survey--1974. J Pediatr Surg 10 (3): 329-37, 1975.  [PUBMED Abstract]

  3. Czauderna P, Mackinlay G, Perilongo G, et al.: Hepatocellular carcinoma in children: results of the first prospective study of the International Society of Pediatric Oncology group. J Clin Oncol 20 (12): 2798-804, 2002.  [PUBMED Abstract]

  4. Zhang Z, Liu Q, He J, et al.: The effect of preoperative transcatheter hepatic arterial chemoembolization on disease-free survival after hepatectomy for hepatocellular carcinoma. Cancer 89 (12): 2606-12, 2000.  [PUBMED Abstract]

  5. Reyes JD, Carr B, Dvorchik I, et al.: Liver transplantation and chemotherapy for hepatoblastoma and hepatocellular cancer in childhood and adolescence. J Pediatr 136 (6): 795-804, 2000.  [PUBMED Abstract]

  6. Bilik R, Superina R: Transplantation for unresectable liver tumors in children. Transplant Proc 29 (7): 2834-5, 1997.  [PUBMED Abstract]

  7. Austin MT, Leys CM, Feurer ID, et al.: Liver transplantation for childhood hepatic malignancy: a review of the United Network for Organ Sharing (UNOS) database. J Pediatr Surg 41 (1): 182-6, 2006.  [PUBMED Abstract]

  8. Romano F, Stroppa P, Bravi M, et al.: Favorable outcome of primary liver transplantation in children with cirrhosis and hepatocellular carcinoma. Pediatr Transplant 15 (6): 573-9, 2011.  [PUBMED Abstract]

  9. Zhou XD, Tang ZY: Cryotherapy for primary liver cancer. Semin Surg Oncol 14 (2): 171-4, 1998.  [PUBMED Abstract]

  10. Lencioni RA, Allgaier HP, Cioni D, et al.: Small hepatocellular carcinoma in cirrhosis: randomized comparison of radio-frequency thermal ablation versus percutaneous ethanol injection. Radiology 228 (1): 235-40, 2003.  [PUBMED Abstract]

  11. Lubienski A: Hepatocellular carcinoma: interventional bridging to liver transplantation. Transplantation 80 (1 Suppl): S113-9, 2005.  [PUBMED Abstract]

  12. Malogolowkin MH, Stanley P, Steele DA, et al.: Feasibility and toxicity of chemoembolization for children with liver tumors. J Clin Oncol 18 (6): 1279-84, 2000.  [PUBMED Abstract]

  13. Laine J, Jalanko H, Saarinen-Pihkala UM, et al.: Successful liver transplantation after induction chemotherapy in children with inoperable, multifocal primary hepatic malignancy. Transplantation 67 (10): 1369-72, 1999.  [PUBMED Abstract]