Journal of Neuro-Oncology

, 91:307 | Cite as

Brain metastases from hepatocellular carcinoma: prognostic factors and outcome

Brain metastasis from HCC
  • Hye Jin Choi
  • Byung Chul Cho
  • Joo Hyuk Sohn
  • Sang Jun Shin
  • Se Hyun Kim
  • Joo Hang Kim
  • Nae Choon YooEmail author
Clinical Study - patient study


Brain metastases from hepatocellular carcinoma are extremely rare. The objectives of the current study were to assess the natural history, outcome, and possible prognostic factors in patients with brain metastases from hepatocellular carcinoma. Between 1995 and 2006, 6,919 patients with hepatocellular carcinoma were treated at Yonsei University Health System. Of those, 62 (0.9%) had a diagnosis of brain metastasis. We carried out a retrospective review of these 62 patients and performed a statistical analysis. The median age at the time patients were diagnosed with brain metastasis was 54 years. Forty-seven patients (76%) were male, and 53 patients had hepatitis B. Median time from diagnosis of hepatocellular carcinoma to brain metastasis was 18.2 months, and 5 patients had brain involvement as their initial presentation. Intracranial hemorrhage was frequently associated (54.8%) with brain metastasis. The most common presenting symptoms were motor weakness, mental change, and headache. Metastases were treated with whole-brain radiation therapy (WBRT) alone in 17 patients and gamma knife surgery alone in 10 patients. Six patients underwent surgical resection and 5 patients were treated with surgical resection followed by WBRT. Twenty-four patients (39%) received steroids only. Median survival after diagnosis of brain metastasis was 6.8 weeks (95% confidence interval: 3.8–9.8 weeks). Univariate analysis showed that treatment modality, number of brain lesions, α-fetoprotein, ECOG performance score, recursive partitioning analysis (RPA) class, and Child-Pugh classification had a statistically significant impact on survival. In multivariate analysis, treatment modality, number of brain lesions, and Child-Pugh classification were statistically significant prognostic factors for survival. The overall prognosis of patients with brain metastases from hepatocellular carcinoma is extremely poor. Nevertheless, some subsets of patients manifested the most favorable survival criteria (single brain metastasis and good liver function); thus, for at least these patients, treatment may result in an improved survival time.


Brain metastasis Hepatocellular carcinoma Prognostic factor 


  1. 1.
    El-Serag HB, Davila JA, Petersen NJ et al (2003) The continuing increase in the incidence of hepatocellular carcinoma in the United States: an update. Ann Intern Med 139:817–823PubMedGoogle Scholar
  2. 2.
    Llovet JM, Burroughs A, Bruix J (2003) Hepatocellular carcinoma. Lancet 362:1907–1917. doi: 10.1016/S0140-6736(03)14964-1 PubMedCrossRefGoogle Scholar
  3. 3.
    Korean National Statistical Office (2004) Annual report of cause of death in 2003. KNSO, SeoulGoogle Scholar
  4. 4.
    Sawaya R (2004) Intracranial metastases: current managment strategies. Blackwell Futura, Malden, MA, USAGoogle Scholar
  5. 5.
    Carr BI (2004) Hepatocellular carcinoma: current management and future trends. Gastroenterology 127(Suppl. 1):S218–S224. doi: 10.1053/j.gastro.2004.09.036 PubMedCrossRefGoogle Scholar
  6. 6.
    Llovet JM, Bruix J (2003) Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology 37:429–442. doi: 10.1053/jhep.2003.50047 PubMedCrossRefGoogle Scholar
  7. 7.
    Gaspar L, Scott C, Rotman M et al (1997) Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys 37:745–751. doi: 10.1016/S0360-3016(96)00619-0 PubMedGoogle Scholar
  8. 8.
    Pugh RN, Murray-Lyon IM, Dawson JL et al (1973) Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 60(8):646–649. doi: 10.1002/bjs.1800600817 PubMedCrossRefGoogle Scholar
  9. 9.
    Uka K, Aikata H, Takaki S et al (2007) Clinical features and prognosis of patients with extrahepatic metastases from hepatocellular carcinoma. World J Gastroenterol 13:414–420PubMedGoogle Scholar
  10. 10.
    Lee YT, Geer DA (1987) Primary liver cancer: pattern of metastasis. J Surg Oncol 36:26–31. doi: 10.1002/jso.2930360107 PubMedCrossRefGoogle Scholar
  11. 11.
    Seinfeld J, Wagner AS, Kleinschmidt-DeMasters BK (2006) Brain metastases from hepatocellular carcinoma in US patients. J Neurooncol 76:93–98. doi: 10.1007/s11060-005-4175-3 PubMedCrossRefGoogle Scholar
  12. 12.
    Kim M, Na DL, Park SH et al (1998) Nervous system involvement by metastatic hepatocellular carcinoma. J Neurooncol 36:85–90. doi: 10.1023/A:1005716408970 PubMedCrossRefGoogle Scholar
  13. 13.
    Murakami K, Nawano S, Moriyama N et al (1996) Intracranial metastases of hepatocellular carcinoma: CT and MRI. Neuroradiology 38(Suppl 1):S31–S35. doi: 10.1007/BF02278115 PubMedCrossRefGoogle Scholar
  14. 14.
    Chen SF, Tsai NW, Lui CC et al (2007) Hepatocellular carcinoma presenting as nervous system involvement. Eur J Neurol 14:408–412. doi: 10.1111/j.1468-1331.2007.01681.x PubMedCrossRefGoogle Scholar
  15. 15.
    Tunc B, Filik L, Tezer-Filik I et al (2004) Brain metastasis of hepatocellular carcinoma: a case report and review of the literature. World J Gastroenterol 10:1688–1689PubMedGoogle Scholar
  16. 16.
    Natsuizaka M, Omura T, Akaike T et al (2005) Clinical features of hepatocellular carcinoma with extrahepatic metastases. J Gastroenterol Hepatol 20:1781–1787. doi: 10.1111/j.1440-1746.2005.03919.x PubMedCrossRefGoogle Scholar
  17. 17.
    Chang L, Chen YL, Kao MC (2004) Intracranial metastasis of hepatocellular carcinoma: review of 45 cases. Surg Neurol 62:172–177. doi: 10.1016/j.surneu.2003.10.002 PubMedCrossRefGoogle Scholar
  18. 18.
    Nomura F, Ohnishi K, Tanabe Y (1989) Clinical features and prognosis of hepatocellular carcinoma with reference to serum alpha-fetoprotein levels. Analysis of 606 patients. Cancer 64:1700–1707. doi:10.1002/1097-0142(19891015)64:8<1700::AID-CNCR2820640824>3.0.CO;2-ZPubMedCrossRefGoogle Scholar
  19. 19.
    Akashi Y, Koreeda C, Enomoto S et al (1991) Prognosis of unresectable hepatocellular carcinoma: an evaluation based on multivariate analysis of 90 cases. Hepatology 14:262–268PubMedCrossRefGoogle Scholar
  20. 20.
    Llado L, Virgili J, Figueras J et al (2000) A prognostic index of the survival of patients with unresectable hepatocellular carcinoma after transcatheter arterial chemoembolization. Cancer 88:50–57. doi:10.1002/(SICI)1097-0142(20000101)88:1<50::AID-CNCR8>3.0.CO;2-IPubMedCrossRefGoogle Scholar
  21. 21.
    Martins A, Cortez-Pinto H, Marques-Vidal P et al (2006) Treatment and prognostic factors in patients with hepatocellular carcinoma. Liver Int 26:680–687. doi: 10.1111/j.1478-3231.2006.001285.x PubMedCrossRefGoogle Scholar
  22. 22.
    Khuntia D, Brown P, Li J et al (2006) Whole-brain radiotherapy in the management of brain metastasis. J Clin Oncol 24:1295–1304. doi: 10.1200/JCO.2005.04.6185 PubMedCrossRefGoogle Scholar
  23. 23.
    Richards GM, Khuntia D, Mehta MP (2007) Therapeutic management of metastatic brain tumors. Crit Rev Oncol Hematol 61:70–78. doi: 10.1016/j.critrevonc.2006.06.012 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Hye Jin Choi
    • 1
  • Byung Chul Cho
    • 1
  • Joo Hyuk Sohn
    • 1
  • Sang Jun Shin
    • 1
  • Se Hyun Kim
    • 1
  • Joo Hang Kim
    • 1
  • Nae Choon Yoo
    • 1
    Email author
  1. 1.Division of OncologyYonsei Cancer Center, Yonsei University College of MedicineSeoulKorea

Personalised recommendations