Skip to main content
Top
Published in: International Journal of Clinical Oncology 6/2019

01-06-2019 | Metastasis | Original Article

Control of intracranial disease is associated with improved survival in patients with brain metastasis from hepatocellular carcinoma

Authors: Hee Chul Nam, Pil Soo Sung, Do Seon Song, Jung Hyun Kwon, Soon Woo Nam, Dong Jin Yoon, Jeong Won Jang, Jong Young Choi, Seung Kew Yoon, Seok Whan Moon, Hong Seok Jang, Jae-Sung Park, Sin-Soo Jeun, Yong-Kil Hong, Si Hyun Bae

Published in: International Journal of Clinical Oncology | Issue 6/2019

Login to get access

Abstract

Background

Brain metastasis is a rare event in patients with hepatocellular carcinoma (HCC). This retrospective study aimed to identify the prognostic factors and determine the outcomes of patients with brain metastases from HCC.

Methods

About 86 patients with brain metastases (0.6%) from HCC were identified from two institutions; of them, 32 underwent tumor-removing surgery or stereotactic radiosurgery (SRS) with or without adjuvant whole brain radiotherapy (WBRT) (group 1), 30 had WBRT alone (group 2), and 24 received conservative treatment (group 3). Estimates for overall survival (OS) after brain metastases were determined, and clinical prognostic factors were identified.

Results

The median OS after development of brain metastases was 50 days. About 75 (87.2%) patients had lung metastases at the time of brain metastasis diagnosis. Group 1 showed better OS, followed by group 2 and group 3, sequentially (p < 0.001). Univariate analyses showed that treatment with curative intent (surgery or SRS), Child–Pugh class A, alpha-fetoprotein level < 400 ng/ml, and recursive partitioning analysis classification I or II were associated with improved survival (p < 0.001, 0.002, 0.029, and 0.012, respectively). Multivariate analysis showed that treatment with curative intent and Child–Pugh class A was associated with improved OS (p < 0.001 and 0.009, respectively).

Conclusion

Although the overall prognosis of patients with brain metastases from HCC is extremely poor, patients actively treated with surgery or radiosurgery have prolonged survival, suggesting that interventions to control intracranial disease are important in these patients.
Literature
1.
go back to reference Heimbach JK, Kulik LM, Finn RS et al (2018) AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology 67:358–380CrossRefPubMed Heimbach JK, Kulik LM, Finn RS et al (2018) AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology 67:358–380CrossRefPubMed
3.
4.
go back to reference Sung PS, Park HL, Yang K et al (2018) (18)F-fluorodeoxyglucose uptake of hepatocellular carcinoma as a prognostic predictor in patients with sorafenib treatment. Eur J Nucl Med Mol Imaging 45:384–391CrossRefPubMed Sung PS, Park HL, Yang K et al (2018) (18)F-fluorodeoxyglucose uptake of hepatocellular carcinoma as a prognostic predictor in patients with sorafenib treatment. Eur J Nucl Med Mol Imaging 45:384–391CrossRefPubMed
5.
go back to reference Seinfeld J, Wagner AS, Kleinschmidt-DeMasters BK (2006) Brain metastases from hepatocellular carcinoma in US patients. J Neurooncol 76:93–98CrossRefPubMed Seinfeld J, Wagner AS, Kleinschmidt-DeMasters BK (2006) Brain metastases from hepatocellular carcinoma in US patients. J Neurooncol 76:93–98CrossRefPubMed
6.
go back to reference Natsuizaka M, Omura T, Akaike T et al (2005) Clinical features of hepatocellular carcinoma with extrahepatic metastases. J Gastroenterol Hepatol 20:1781–1787CrossRefPubMed Natsuizaka M, Omura T, Akaike T et al (2005) Clinical features of hepatocellular carcinoma with extrahepatic metastases. J Gastroenterol Hepatol 20:1781–1787CrossRefPubMed
7.
go back to reference Chan KM, Yu MC, Wu TJ et al (2009) Efficacy of surgical resection in management of isolated extrahepatic metastases of hepatocellular carcinoma. World J Gastroenterol 15:5481–5488CrossRefPubMedPubMedCentral Chan KM, Yu MC, Wu TJ et al (2009) Efficacy of surgical resection in management of isolated extrahepatic metastases of hepatocellular carcinoma. World J Gastroenterol 15:5481–5488CrossRefPubMedPubMedCentral
8.
go back to reference Lim S, Lee S, Lim JY et al (2014) Hepatocellular carcinoma specific graded prognostic assessment can predict outcomes for patients with brain metastases from hepatocellular carcinoma. J Neurooncol 120:199–207CrossRefPubMed Lim S, Lee S, Lim JY et al (2014) Hepatocellular carcinoma specific graded prognostic assessment can predict outcomes for patients with brain metastases from hepatocellular carcinoma. J Neurooncol 120:199–207CrossRefPubMed
9.
go back to reference Kim M, Na DL, Park SH et al (1998) Nervous system involvement by metastatic hepatocellular carcinoma. J Neurooncol 36:85–90CrossRefPubMed Kim M, Na DL, Park SH et al (1998) Nervous system involvement by metastatic hepatocellular carcinoma. J Neurooncol 36:85–90CrossRefPubMed
10.
go back to reference Si MS, Amersi F, Golish SR et al (2003) Prevalence of metastases in hepatocellular carcinoma: risk factors and impact on survival. Am Surg 69:879–885PubMed Si MS, Amersi F, Golish SR et al (2003) Prevalence of metastases in hepatocellular carcinoma: risk factors and impact on survival. Am Surg 69:879–885PubMed
11.
go back to reference Kawaguchi T, Endo M, Yokoya S et al (1982) Difference in proliferation-kinetics between tumor cells arrested in the brain and liver. Experientia 38:1236–1237CrossRefPubMed Kawaguchi T, Endo M, Yokoya S et al (1982) Difference in proliferation-kinetics between tumor cells arrested in the brain and liver. Experientia 38:1236–1237CrossRefPubMed
12.
13.
go back to reference Choi HJ, Cho BC, Sohn JH et al (2009) Brain metastases from hepatocellular carcinoma: prognostic factors and outcome: brain metastasis from HCC. J Neurooncol 91:307–313CrossRefPubMed Choi HJ, Cho BC, Sohn JH et al (2009) Brain metastases from hepatocellular carcinoma: prognostic factors and outcome: brain metastasis from HCC. J Neurooncol 91:307–313CrossRefPubMed
14.
15.
go back to reference Hsiao SY, Chen SF, Chang CC et al (2011) Central nervous system involvement in hepatocellular carcinoma: clinical characteristics and comparison of intracranial and spinal metastatic groups. J Clin Neurosci 18:364–368CrossRefPubMed Hsiao SY, Chen SF, Chang CC et al (2011) Central nervous system involvement in hepatocellular carcinoma: clinical characteristics and comparison of intracranial and spinal metastatic groups. J Clin Neurosci 18:364–368CrossRefPubMed
16.
go back to reference Chang L, Chen YL, Kao MC (2004) Intracranial metastasis of hepatocellular carcinoma: review of 45 cases. Surg Neurol 62:172–177CrossRefPubMed Chang L, Chen YL, Kao MC (2004) Intracranial metastasis of hepatocellular carcinoma: review of 45 cases. Surg Neurol 62:172–177CrossRefPubMed
17.
go back to reference Han JH, Kim DG, Park JC et al (2010) Little response of cerebral metastasis from hepatocellular carcinoma to any treatments. J Korean Neurosurg Soc 47:325–331CrossRefPubMedPubMedCentral Han JH, Kim DG, Park JC et al (2010) Little response of cerebral metastasis from hepatocellular carcinoma to any treatments. J Korean Neurosurg Soc 47:325–331CrossRefPubMedPubMedCentral
18.
go back to reference Park Y, Kim KS, Kim K et al (2015) Nomogram prediction of survival in patients with brain metastases from hepatocellular carcinoma treated with whole-brain radiotherapy: a multicenter retrospective study. J Neurooncol 125:377–383CrossRefPubMed Park Y, Kim KS, Kim K et al (2015) Nomogram prediction of survival in patients with brain metastases from hepatocellular carcinoma treated with whole-brain radiotherapy: a multicenter retrospective study. J Neurooncol 125:377–383CrossRefPubMed
19.
go back to reference Hsieh MJ, Lu CH, Tsai NW et al (2009) Prediction, clinical characteristics and prognosis of intracerebral hemorrhage in hepatocellular carcinoma patients with intracerebral metastasis. J Clin Neurosci 16:394–398CrossRefPubMed Hsieh MJ, Lu CH, Tsai NW et al (2009) Prediction, clinical characteristics and prognosis of intracerebral hemorrhage in hepatocellular carcinoma patients with intracerebral metastasis. J Clin Neurosci 16:394–398CrossRefPubMed
20.
go back to reference Kim KS, Kim K, Chie EK et al (2014) Prognostic stratification of brain metastases from hepatocellular carcinoma. J Neurooncol 120:209–214CrossRefPubMed Kim KS, Kim K, Chie EK et al (2014) Prognostic stratification of brain metastases from hepatocellular carcinoma. J Neurooncol 120:209–214CrossRefPubMed
21.
go back to reference Yamakawa Y, Moriguchi M, Aramaki T et al (2015) Brain metastasis from hepatocellular carcinoma: the impact of radiotherapy on control of intracranial hemorrhage. Hepatol Res 45:1071–1075CrossRefPubMed Yamakawa Y, Moriguchi M, Aramaki T et al (2015) Brain metastasis from hepatocellular carcinoma: the impact of radiotherapy on control of intracranial hemorrhage. Hepatol Res 45:1071–1075CrossRefPubMed
22.
go back to reference Ogino A, Hirai T, Serizawa T et al (2018) Clinical features of brain metastases from hepatocellular carcinoma using gamma knife surgery. Acta Neurochir 160:997–1003CrossRefPubMed Ogino A, Hirai T, Serizawa T et al (2018) Clinical features of brain metastases from hepatocellular carcinoma using gamma knife surgery. Acta Neurochir 160:997–1003CrossRefPubMed
24.
go back to reference Park ES, Kwon DH, Park JB et al (2014) Gamma knife surgery for treating brain metastases arising from hepatocellular carcinomas. J Neurosurg 121(Suppl):102–109CrossRefPubMed Park ES, Kwon DH, Park JB et al (2014) Gamma knife surgery for treating brain metastases arising from hepatocellular carcinomas. J Neurosurg 121(Suppl):102–109CrossRefPubMed
25.
go back to reference 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 37:745–751CrossRefPubMed 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 37:745–751CrossRefPubMed
26.
go back to reference Chen SF, Tsai NW, Lui CC et al (2007) Hepatocellular carcinoma presenting as nervous system involvement. Eur J Neurol 14:408–412CrossRefPubMed Chen SF, Tsai NW, Lui CC et al (2007) Hepatocellular carcinoma presenting as nervous system involvement. Eur J Neurol 14:408–412CrossRefPubMed
27.
go back to reference Wang S, Wang A, Lin J et al (2017) Brain metastases from hepatocellular carcinoma: recent advances and future avenues. Oncotarget 8:25814–25829PubMedPubMedCentral Wang S, Wang A, Lin J et al (2017) Brain metastases from hepatocellular carcinoma: recent advances and future avenues. Oncotarget 8:25814–25829PubMedPubMedCentral
28.
go back to reference Uchino K, Tateishi R, Shiina S et al (2011) Hepatocellular carcinoma with extrahepatic metastasis: clinical features and prognostic factors. Cancer 117:4475–4483CrossRefPubMed Uchino K, Tateishi R, Shiina S et al (2011) Hepatocellular carcinoma with extrahepatic metastasis: clinical features and prognostic factors. Cancer 117:4475–4483CrossRefPubMed
29.
go back to reference Jung SM, Jang JW, You CR et al (2012) Role of intrahepatic tumor control in the prognosis of patients with hepatocellular carcinoma and extrahepatic metastases. J Gastroenterol Hepatol 27:684–689CrossRefPubMed Jung SM, Jang JW, You CR et al (2012) Role of intrahepatic tumor control in the prognosis of patients with hepatocellular carcinoma and extrahepatic metastases. J Gastroenterol Hepatol 27:684–689CrossRefPubMed
30.
go back to reference Yoo DJ, Kim KM, Jin YJ et al (2011) Clinical outcome of 251 patients with extrahepatic metastasis at initial diagnosis of hepatocellular carcinoma: does transarterial chemoembolization improve survival in these patients? J Gastroenterol Hepatol 26:145–154CrossRefPubMed Yoo DJ, Kim KM, Jin YJ et al (2011) Clinical outcome of 251 patients with extrahepatic metastasis at initial diagnosis of hepatocellular carcinoma: does transarterial chemoembolization improve survival in these patients? J Gastroenterol Hepatol 26:145–154CrossRefPubMed
31.
go back to reference Yoo JJ, Lee JH, Lee SH et al (2014) Comparison of the effects of transarterial chemoembolization for advanced hepatocellular carcinoma between patients with and without extrahepatic metastases. PLoS One 9:e113926CrossRefPubMedPubMedCentral Yoo JJ, Lee JH, Lee SH et al (2014) Comparison of the effects of transarterial chemoembolization for advanced hepatocellular carcinoma between patients with and without extrahepatic metastases. PLoS One 9:e113926CrossRefPubMedPubMedCentral
32.
go back to reference Park TY, Na YC, Lee WH et al (2013) Treatment options of metastatic brain tumors from hepatocellular carcinoma: surgical resection vs. gamma knife radiosurgery vs. whole brain radiation therapy. Brain Tumor Res Treat 1:78–84CrossRefPubMedPubMedCentral Park TY, Na YC, Lee WH et al (2013) Treatment options of metastatic brain tumors from hepatocellular carcinoma: surgical resection vs. gamma knife radiosurgery vs. whole brain radiation therapy. Brain Tumor Res Treat 1:78–84CrossRefPubMedPubMedCentral
33.
go back to reference Lin Y, Huang S-T, Jiang Y-M et al (2017) Hemorrhage of brain metastasis is a poor prognostic factor in hepatocellular carcinoma patients. Oncotarget 8:93245PubMedPubMedCentral Lin Y, Huang S-T, Jiang Y-M et al (2017) Hemorrhage of brain metastasis is a poor prognostic factor in hepatocellular carcinoma patients. Oncotarget 8:93245PubMedPubMedCentral
Metadata
Title
Control of intracranial disease is associated with improved survival in patients with brain metastasis from hepatocellular carcinoma
Authors
Hee Chul Nam
Pil Soo Sung
Do Seon Song
Jung Hyun Kwon
Soon Woo Nam
Dong Jin Yoon
Jeong Won Jang
Jong Young Choi
Seung Kew Yoon
Seok Whan Moon
Hong Seok Jang
Jae-Sung Park
Sin-Soo Jeun
Yong-Kil Hong
Si Hyun Bae
Publication date
01-06-2019
Publisher
Springer Singapore
Published in
International Journal of Clinical Oncology / Issue 6/2019
Print ISSN: 1341-9625
Electronic ISSN: 1437-7772
DOI
https://doi.org/10.1007/s10147-019-01407-z

Other articles of this Issue 6/2019

International Journal of Clinical Oncology 6/2019 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine