General Medical Information

Childhood Liver Cancer

April 16, 2007 on 1:21 pm | In Cancer |

This treatment information summary on childhood liver cancer is an overview of prognosis, diagnosis, classification, and treatment. The National Cancer Institute created the PDQ database to increase the availability of new treatment information and its use in treating patients. Information and references from the most recently published literature are included after review by pediatric oncology specialists.

Cancer in children and adolescents is rare. Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team incorporates the skills of the primary care physician, pediatric surgical subspecialists, radiation therapists, pediatric oncologists/hematologists, rehabilitation specialists, pediatric nurse specialists, social workers, and others in order to ensure that children receive treatment, supportive care, and rehabilitation that will achieve optimal survival and quality of life. Guidelines for pediatric cancer centers and their role in the treatment of pediatric patients with cancer have been outlined by the American Academy of Pediatrics.[1] At these pediatric cancer centers, clinical trials are available for most of the types of cancer that occur in children and adolescents, and the opportunity to participate in these trials is offered to most patients/families. Clinical trials for children and adolescents with cancer are generally designed to compare potentially better therapy with therapy that is currently accepted as standard. The majority of the progress made in identifying curative therapies for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI Web site.
Liver cancer, a rare malignancy in children and adolescents, is divided into 2 major histologic subgroups: hepatoblastoma and hepatocellular carcinoma. The age of onset of liver cancer in children is related to the histology of the tumor. Hepatoblastomas usually occur before 3 years of age, whereas the incidence of hepatocellular carcinoma in the United States varies little with age between 0 and 19 years.[2] The overall survival rate for children with hepatoblastoma is 70%[3-5] but is only 25% for hepatocellular carcinoma.[6]

If a hepatoblastoma is completely removed, the majority of patients survive, but only a minority of patients have lesions amenable to complete resection at diagnosis. The inability to completely remove the primary tumor or the presence of metastatic disease is associated with a poor outcome. Hepatoblastoma is most often unifocal, while hepatocellular carcinoma is often extensively invasive or multicentric. Therefore, resection is possible more often in hepatoblastoma than hepatocellular carcinoma, in which less than 30% are resectable.[7]

The majority of patients with either hepatoblastoma or hepatocellular carcinoma have a serum tumor marker, alpha-fetoprotein, that parallels disease activity. Lack of a significant decrease of alpha-fetoprotein levels with treatment may predict a poor response to therapy.[8] Absence of elevated alpha-fetoprotein may be a poor prognostic sign in hepatoblastoma; it is associated with the small-cell (anaplastic) histologic variant, which responds very poorly to therapy. Occasionally hepatoblastomas produce beta-human chorionic gonadotropin resulting in isosexual precocity. Severe osteopenia is not uncommon. Hepatoblastoma is part of the constellation of findings associated with the Beckwith-Wiedemann syndrome.[9] Loss of the allele of maternal origin at the 11p15.5 familial Beckwith-Wiedemann syndrome locus occurs in many hepatoblastomas. Thus, the genetic abnormality that results in Beckwith-Wiedemann may be directly involved in the pathogenesis in some cases of hepatoblastoma, and imprinting may play a role.[10,11] About 2% of children with hepatoblastoma have hemihypertrophy.[12] Less than 1% of children with hemihypertrophy are at increased risk for developing hepatoblastoma within the first several years of life.[13] There is a clear association between hepatoblastoma and familial adenomatous polyposis (FAP); children in families that carry the FAP gene are at an increased risk for hepatoblastoma, although it occurs in less than 1% of FAP family members.[14-16] Childhood hepatoblastomas frequently have mutations in the beta-catenin gene, the function of which is closely related to FAP.[17] A relationship between very low birth weight and hepatoblastoma has been reported.[18,19]

Hepatocellular carcinoma is associated with hepatitis B and C infection,[20,21] especially in children with perinatally acquired virus. Therefore, widespread hepatitis B immunization may decrease the incidence of hepatocellular carcinoma.[22] Compared to adults, the incubation period from hepatitis virus infection to the genesis of hepatocellular carcinoma is extremely short in some children with perinatally acquired virus. Mutations in the Met/hepatocyte growth factor gene occur in childhood hepatocellular carcinoma, and this could be the mechanism that results in a shortened incubation period.[23] Several specific types of nonviral liver injury and cirrhosis in children are associated with hepatocellular carcinoma: tyrosinemia, biliary cirrhosis, and alpha-1-antitrypsin deficiency.

References

1. Guidelines for the pediatric cancer center and role of such centers in diagnosis and treatment. American Academy of Pediatrics Section Statement Section on Hematology/Oncology. Pediatrics 99 (1): 139-41, 1997.

2. Ries LA, Smith MA, Gurney JG, et al., eds.: Cancer incidence and survival among children and adolescents: United States SEER Program 1975-1995. Bethesda, Md: National Cancer Institute, SEER Program, 1999. NIH Pub.No. 99-4649. Available online. Last accessed April 25, 2002.

3. Ortega JA, Krailo MD, Haas JE, et al.: Effective treatment of unresectable or metastatic hepatoblastoma with cisplatin and continuous infusion doxorubicin chemotherapy: a report from the Childrens Cancer Study Group. J Clin Oncol 9 (12): 2167-76, 1991.

4. Douglass EC, Reynolds M, Finegold M, et al.: Cisplatin, vincristine, and fluorouracil therapy for hepatoblastoma: a Pediatric Oncology Group study. J Clin Oncol 11 (1): 96-9, 1993.

5. Ortega JA, Douglass EC, Feusner JH, et al.: Randomized comparison of cisplatin/vincristine/fluorouracil and cisplatin/continuous infusion doxorubicin for treatment of pediatric hepatoblastoma: A report from the Children’s Cancer Group and the Pediatric Oncology Group. J Clin Oncol 18 (14): 2665-75, 2000.

6. Douglass E, Ortega J, Feusner J, et al.: Hepatocellular carcinoma (HCA) in children and adolescents: results from the Pediatric Intergroup Hepatoma Study (CCG 8881/POG 8945). [Abstract] Proceedings of the American Society of Clinical Oncology 13: A-1439, 420, 1994.

7. 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): 329-337, 1975.

8. Van Tornout JM, Buckley JD, Quinn JJ, et al.: Timing and magnitude of decline in alpha-fetoprotein levels in treated children with unresectable or metastatic hepatoblastoma are predictors of outcome: a report from the Children’s Cancer Group. J Clin Oncol 15 (3): 1190-7, 1997.

9. Sotelo-Avila C, Gonzalez-Crussi F, Fowler JW: Complete and incomplete forms of Beckwith-Wiedemann syndrome: their oncogenic potential. J Pediatr 96 (1): 47-50, 1980.

10. Albrecht S, von Schweinitz D, Waha A, et al.: Loss of maternal alleles on chromosome arm 11p in hepatoblastoma. Cancer Res 54 (19): 5041-4, 1994.

11. Mannens M, Hoovers JM, Redeker E, et al.: Parental imprinting of human chromosome region 11p15.3-pter involved in the Beckwith-Wiedemann syndrome and various human neoplasia. Eur J Hum Genet 2 (1): 3-23, 1994.

12. Fraumeni JF, Miller RW, Hill JA: Primary carcinoma of the liver in childhood: an epidemiologic study. J Natl Cancer Inst 40(5): 1087-1099, 1968.

13. Hoyme HE, Seaver LH, Jones KL, et al.: Isolated hemihyperplasia (hemihypertrophy): report of a prospective multicenter study of the incidence of neoplasia and review. Am J Med Genet 79 (4): 274-8, 1998.

14. Iwama T, Mishima Y: Mortality in young first-degree relatives of patients with familial adenomatous polyposis. Cancer 73 (8): 2065-8, 1994.

15. Li FP, Thurber WA, Seddon J, et al.: Hepatoblastoma in families with polyposis coli. JAMA 257 (18): 2475-7, 1987.

16. Garber JE, Li FP, Kingston JE, et al.: Hepatoblastoma and familial adenomatous polyposis. J Natl Cancer Inst 80 (20): 1626-8, 1988.

17. Koch A, Denkhaus D, Albrecht S, et al.: Childhood hepatoblastomas frequently carry a mutated degradation targeting box of the beta-catenin gene. Cancer Res 59 (2): 269-73, 1999.

18. Ikeda H, Hachitanda Y, Tanimura M, et al.: Development of unfavorable hepatoblastoma in children of very low birth weight: results of a surgical and pathologic review. Cancer 82 (9): 1789-96, 1998.

19. Maruyama K, Ikeda H, Koizumi T, et al.: Prenatal and postnatal histories of very low birthweight infants who developed hepatoblastoma. Pediatr Int 41 (1): 82-9, 1999.

20. Ni YH, Chang MH, Hsu HY, et al.: Hepatocellular carcinoma in childhood. Clinical manifestations and prognosis. Cancer 68 (8): 1737-41, 1991.

21. Tsukuma H, Hiyama T, Tanaka S, et al.: Risk factors for hepatocellular carcinoma among patients with chronic liver disease. N Engl J Med 328 (25): 1797-801, 1993.

22. Chang MH, Chen CJ, Lai MS, et al.: Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. Taiwan Childhood Hepatoma Study Group. N Engl J Med 336 (26): 1855-9, 1997.

23. Park WS, Dong SM, Kim SY, et al.: Somatic mutations in the kinase domain of the Met/hepatocyte growth factor receptor gene in childhood hepatocellular carcinomas. Cancer Res 59 (2): 307-10, 1999.