Skip to main content
Top
Published in: Tumor Biology 1/2012

01-02-2012 | Research Article

Prognostic relevance of oncological serum biomarkers in liver cancer patients undergoing transarterial chemoembolization therapy

Authors: Nikolaus Kohles, Dorothea Nagel, Dietrich Jüngst, Jürgen Durner, Petra Stieber, Stefan Holdenrieder

Published in: Tumor Biology | Issue 1/2012

Login to get access

Abstract

As transarterial chemoembolization (TACE) therapy is an effective locoregional treatment for patients with advanced liver cancer, prognostic biomarkers are highly needed for pretherapeutic stratification of patients to TACE therapy. Sera of 50 prospectively and consecutively included patients with hepatocellular carcinoma (HCC) undergoing TACE were taken before and 24 h after TACE application. Levels of liver-specific, tumor-related, and cell death biomarkers were analyzed and correlated with overall patient survival. The study was particularly focused on patients treated by TACE with palliative intention (N = 38). Sixteen of 38 patients died within 1 year after TACE, 22 were still alive. In univariate analysis, high levels of cytokeratin 19-fragments (CYFRA 21-1), alpha fetoprotein (AFP), and low choline esterase (CHE) levels measured before and 24 h after TACE were correlated with unfavorable outcome. Further high pretherapeutic lactate dehydrogenase (LDH), aspartate-aminotransferase, and bilirubin levels as well as high 24 h C-reactive protein values were associated with poor survival. In multivariate analysis of clinical and only pretherapeutic biomarkers, AFP, CHE, and LDH showed to be independent prognostic parameters. When additionally 24 h values were included, CHE (24 h) and AFP (24 h) were the strongest independent prognostic biomarkers with a slightly higher prognostic power (Akaike’s information criterion 90.3 vs. 92.7). The combination of AFP, CHE, and LDH enables efficient pretherapeutic stratification of HCC patients in advanced tumor stage for TACE therapy.
Literature
1.
go back to reference Hellerbrand C, Hartmann A, Richter G, Knoll A, Wiest R, Scholmerich J, et al. Hepatocellular carcinoma in southern Germany: epidemiological and clinicopathological characteristics and risk factors. Digest Dis. 2001;19:345–51.CrossRef Hellerbrand C, Hartmann A, Richter G, Knoll A, Wiest R, Scholmerich J, et al. Hepatocellular carcinoma in southern Germany: epidemiological and clinicopathological characteristics and risk factors. Digest Dis. 2001;19:345–51.CrossRef
2.
go back to reference Tsukuma H, Hiyama T, Tanaka S, Nakao M, Yabuuchi T, Kitamura T, et al. Risk factors for hepatocellular carcinoma among patients with chronic liver disease. N Engl J Med. 1993;328:1797–801.PubMedCrossRef Tsukuma H, Hiyama T, Tanaka S, Nakao M, Yabuuchi T, Kitamura T, et al. Risk factors for hepatocellular carcinoma among patients with chronic liver disease. N Engl J Med. 1993;328:1797–801.PubMedCrossRef
3.
go back to reference Velazquez RF, Rodriguez M, Navascues CA, Linares A, Perez R, Sotorrios NG, et al. Prospective analysis of risk factors for hepatocellular carcinoma in patients with liver cirrhosis. Hepatol. 1993;37:520–7.CrossRef Velazquez RF, Rodriguez M, Navascues CA, Linares A, Perez R, Sotorrios NG, et al. Prospective analysis of risk factors for hepatocellular carcinoma in patients with liver cirrhosis. Hepatol. 1993;37:520–7.CrossRef
4.
go back to reference Parkin DM, Bray F, Ferlay J, Pisani P. Estimating the world cancer burden: GLOBOCAN 2000. Int J Cancer. 2001;94:153–6.PubMedCrossRef Parkin DM, Bray F, Ferlay J, Pisani P. Estimating the world cancer burden: GLOBOCAN 2000. Int J Cancer. 2001;94:153–6.PubMedCrossRef
5.
go back to reference El-Serag HB, Mason AC. Hepatocellular carcinoma is rising in the United States. Gastroenterol. 1999;116:G0235.CrossRef El-Serag HB, Mason AC. Hepatocellular carcinoma is rising in the United States. Gastroenterol. 1999;116:G0235.CrossRef
6.
go back to reference El-Serag HB, Marrero JA, Rudolph L, Reddy KR. Diagnosis and treatment of hepatocellular carcinoma. Gastroenterol. 2008;134:1752–63.CrossRef El-Serag HB, Marrero JA, Rudolph L, Reddy KR. Diagnosis and treatment of hepatocellular carcinoma. Gastroenterol. 2008;134:1752–63.CrossRef
7.
go back to reference Forner A, Hessheimer AJ, Real MI, Bruix J. Treatment of hepatocellular carcinoma. Crit Rev Oncol Hematol. 2006;60:89–98.PubMedCrossRef Forner A, Hessheimer AJ, Real MI, Bruix J. Treatment of hepatocellular carcinoma. Crit Rev Oncol Hematol. 2006;60:89–98.PubMedCrossRef
8.
go back to reference Bruix J, Llovet JM, Castells A, Montana X, Bru C, Ayuso MD, et al. Transarterial embolization versus symptomatic treatment in patients with advanced hepatocellular carcinoma: results of a randomized, controlled trial in a single institution. Hepatol. 1998;27:1578–83.CrossRef Bruix J, Llovet JM, Castells A, Montana X, Bru C, Ayuso MD, et al. Transarterial embolization versus symptomatic treatment in patients with advanced hepatocellular carcinoma: results of a randomized, controlled trial in a single institution. Hepatol. 1998;27:1578–83.CrossRef
9.
go back to reference Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatol. 2003;37:429–42.CrossRef Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatol. 2003;37:429–42.CrossRef
10.
go back to reference Llovet JM, Real MI, Montana X, Planas R, Coll S, Aponte J, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet. 2002;359:1734–9.PubMedCrossRef Llovet JM, Real MI, Montana X, Planas R, Coll S, Aponte J, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet. 2002;359:1734–9.PubMedCrossRef
11.
go back to reference Anonymous. A comparison of lipiodol chemoembolization and conservative treatment for unresectable hepatocellular carcinoma. Groupe d’Etude et de Traitement du Carcinome Hépatocellulaire. N Engl J Med. 1995;332:1256–61.CrossRef Anonymous. A comparison of lipiodol chemoembolization and conservative treatment for unresectable hepatocellular carcinoma. Groupe d’Etude et de Traitement du Carcinome Hépatocellulaire. N Engl J Med. 1995;332:1256–61.CrossRef
12.
go back to reference Pelletier G, Ducreux M, Gay F, Luboinski M, Hagege H, Dao T, et al. Treatment of unresectable hepatocellular carcinoma with lipiodol chemoembolization: a multicenter randomized trial. J Hepatol. 1998;29:129–34.PubMedCrossRef Pelletier G, Ducreux M, Gay F, Luboinski M, Hagege H, Dao T, et al. Treatment of unresectable hepatocellular carcinoma with lipiodol chemoembolization: a multicenter randomized trial. J Hepatol. 1998;29:129–34.PubMedCrossRef
13.
go back to reference Takayasu K, Arii S, Ikao I, Omata M, Okita K, Ichida T, et al. Prospective cohort study of transarterial chemoembolization for unresectable hepatocellular carcinoma in 8510 patients. Gastroenterol. 2006;131:461–9.CrossRef Takayasu K, Arii S, Ikao I, Omata M, Okita K, Ichida T, et al. Prospective cohort study of transarterial chemoembolization for unresectable hepatocellular carcinoma in 8510 patients. Gastroenterol. 2006;131:461–9.CrossRef
14.
go back to reference Bruix JSM, Llovet JM. Chemoembolization for hepatocellular carcinoma. Gastroenterol. 2004;127:179–88.CrossRef Bruix JSM, Llovet JM. Chemoembolization for hepatocellular carcinoma. Gastroenterol. 2004;127:179–88.CrossRef
15.
go back to reference Lim HS, Jeong YY, Kang HK, Kim JK, Park JG. Imaging features of hepatocellular carcinoma after transcatheter arterial chemoembolization and radiofrequency ablation. Am J Roentgenol. 2006;187:W341–9.CrossRef Lim HS, Jeong YY, Kang HK, Kim JK, Park JG. Imaging features of hepatocellular carcinoma after transcatheter arterial chemoembolization and radiofrequency ablation. Am J Roentgenol. 2006;187:W341–9.CrossRef
16.
go back to reference Takayasu K, Arii S, Matsuo N, Yoshikawa M, Ryu M, Takasaki K, et al. Comparison of CT findings with resected specimens after chemoembolization with iodized oil for hepatocellular carcinoma. Am J Roentgenol. 2000;175:699–704. Takayasu K, Arii S, Matsuo N, Yoshikawa M, Ryu M, Takasaki K, et al. Comparison of CT findings with resected specimens after chemoembolization with iodized oil for hepatocellular carcinoma. Am J Roentgenol. 2000;175:699–704.
17.
go back to reference Thabet A, Kalva S, Gervais DA. Percutaneous image-guided therapy of intra-abdominal malignancy: imaging evaluation of treatment response. Abdom Imaging. 2009;34:593–609.PubMedCrossRef Thabet A, Kalva S, Gervais DA. Percutaneous image-guided therapy of intra-abdominal malignancy: imaging evaluation of treatment response. Abdom Imaging. 2009;34:593–609.PubMedCrossRef
18.
go back to reference Holdenrieder S, Stieber P, von Pawel J, Raith H, Nagel D, Feldmann K, et al. Early and specific prediction of the therapeutic efficacy in lung cancer by nucleosomal DNA and cytokeratin 19 fragments. Ann N Y Acad Sci. 2006;1075:244–75.PubMedCrossRef Holdenrieder S, Stieber P, von Pawel J, Raith H, Nagel D, Feldmann K, et al. Early and specific prediction of the therapeutic efficacy in lung cancer by nucleosomal DNA and cytokeratin 19 fragments. Ann N Y Acad Sci. 2006;1075:244–75.PubMedCrossRef
19.
go back to reference Holdenrieder S, von Pawel J, Dankelmann E, Duell T, Faderl B, Markus A, et al. Nucleosomes and CYFRA 21-1 indicate tumor response after one cycle of chemotherapy in recurrent non-small cell lung cancer. Lung Cancer. 2009;63:128–35.PubMedCrossRef Holdenrieder S, von Pawel J, Dankelmann E, Duell T, Faderl B, Markus A, et al. Nucleosomes and CYFRA 21-1 indicate tumor response after one cycle of chemotherapy in recurrent non-small cell lung cancer. Lung Cancer. 2009;63:128–35.PubMedCrossRef
20.
go back to reference Holdenrieder S, von Pawel J, Dankelmann E, Duell T, Faderl B, Markus A, et al. Nucleosomes, ProGRP, NSE, CYFRA 21-1 and CEA in the therapy monitoring of small-cell lung cancer during first-line chemotherapy. Clin Cancer Res. 2008;14:7813–21.PubMedCrossRef Holdenrieder S, von Pawel J, Dankelmann E, Duell T, Faderl B, Markus A, et al. Nucleosomes, ProGRP, NSE, CYFRA 21-1 and CEA in the therapy monitoring of small-cell lung cancer during first-line chemotherapy. Clin Cancer Res. 2008;14:7813–21.PubMedCrossRef
21.
go back to reference Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK, et al. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL Conference. J Hepatol. 2001;35:421–30.PubMedCrossRef Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK, et al. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL Conference. J Hepatol. 2001;35:421–30.PubMedCrossRef
22.
go back to reference Holdenrieder S, Stieber P, Bodenmuller H, Fertig G, Furst H, Schmeller N, et al. Nucleosomes in serum as a marker for cell death. Clin Chem Lab Med. 2001;39:596–605.PubMedCrossRef Holdenrieder S, Stieber P, Bodenmuller H, Fertig G, Furst H, Schmeller N, et al. Nucleosomes in serum as a marker for cell death. Clin Chem Lab Med. 2001;39:596–605.PubMedCrossRef
23.
go back to reference Vogl TJ, Vogl TJ, Naguib NNN, Nour-Eldin NEA, Rao P, Emami AH, et al. Review on transarterial chemoembolization in hepatocellular carcinoma: palliative, combined, neoadjuvant, bridging, and symptomatic indications. Eur J Radiol. 2009;72:505–16.PubMedCrossRef Vogl TJ, Vogl TJ, Naguib NNN, Nour-Eldin NEA, Rao P, Emami AH, et al. Review on transarterial chemoembolization in hepatocellular carcinoma: palliative, combined, neoadjuvant, bridging, and symptomatic indications. Eur J Radiol. 2009;72:505–16.PubMedCrossRef
24.
go back to reference Meyn RE, Stephens LC, Ang KK, Hunter NR, Brock WA, Milas L, et al. Heterogeneity in the development of apoptosis in irradiated murine tumors of different histologies. Int J Rad Biol. 1993;64:583–91.PubMedCrossRef Meyn RE, Stephens LC, Ang KK, Hunter NR, Brock WA, Milas L, et al. Heterogeneity in the development of apoptosis in irradiated murine tumors of different histologies. Int J Rad Biol. 1993;64:583–91.PubMedCrossRef
25.
go back to reference Fabregat I. Dysregulation of apoptosis in hepatocellular carcinoma cells. World J Gastroenterol. 2009;15:513–20.PubMedCrossRef Fabregat I. Dysregulation of apoptosis in hepatocellular carcinoma cells. World J Gastroenterol. 2009;15:513–20.PubMedCrossRef
26.
go back to reference Jing Z, Nan KJ, Hu ML. Cell proliferation, apoptosis and the related regulators p27, p53 expression in hepatocellular carcinoma. World J Gastroenterol. 2005;11:1910–6.PubMed Jing Z, Nan KJ, Hu ML. Cell proliferation, apoptosis and the related regulators p27, p53 expression in hepatocellular carcinoma. World J Gastroenterol. 2005;11:1910–6.PubMed
27.
go back to reference Kohles N, Jüngst D, Durner J, Nagel D, Stieber P, Holdenrieder S. Predictive value of circulating nucleosomes and oncological biomarkers in liver cancer patients undergoing transarterial chemoembolisation therapy. BMC Cancer. 2011;11:202.PubMedCrossRef Kohles N, Jüngst D, Durner J, Nagel D, Stieber P, Holdenrieder S. Predictive value of circulating nucleosomes and oncological biomarkers in liver cancer patients undergoing transarterial chemoembolisation therapy. BMC Cancer. 2011;11:202.PubMedCrossRef
28.
go back to reference Ren N, Ye QH, Qin LX, Zhang BH, Liu YK, Tang ZY. Circulating DNA level is negatively associated with the long-term survival of hepatocellular carcinoma patients. World J Gastroenterol. 2006;12:3911–4.PubMed Ren N, Ye QH, Qin LX, Zhang BH, Liu YK, Tang ZY. Circulating DNA level is negatively associated with the long-term survival of hepatocellular carcinoma patients. World J Gastroenterol. 2006;12:3911–4.PubMed
29.
go back to reference Sozzi G, Conte D, Mariani L, Lo Vullo S, Roz L, Lombardo C, et al. Analysis of circulating tumor DNA in plasma at diagnosis and during follow-up of lung cancer patients. Cancer Res. 2001;61:4675–8.PubMed Sozzi G, Conte D, Mariani L, Lo Vullo S, Roz L, Lombardo C, et al. Analysis of circulating tumor DNA in plasma at diagnosis and during follow-up of lung cancer patients. Cancer Res. 2001;61:4675–8.PubMed
30.
go back to reference Gautschi O, Bigosch C, Huegli B, Jermann M, Marx A, Chasse E, et al. Circulating deoxyribonucleic acid as prognostic marker in non-small-cell lung cancer patients undergoing chemotherapy. J Clin Oncol. 2004;22:4157–64.PubMedCrossRef Gautschi O, Bigosch C, Huegli B, Jermann M, Marx A, Chasse E, et al. Circulating deoxyribonucleic acid as prognostic marker in non-small-cell lung cancer patients undergoing chemotherapy. J Clin Oncol. 2004;22:4157–64.PubMedCrossRef
31.
go back to reference Llado L, Virgili J, Figueras J, Valls C, Dominguez J, Rafecas A, et al. A prognostic index of the survival of patients with unresectable hepatocellular carcinoma after transcatheter arterial chemoembolization. Cancer. 2000;88:50–7.PubMedCrossRef Llado L, Virgili J, Figueras J, Valls C, Dominguez J, Rafecas A, et al. A prognostic index of the survival of patients with unresectable hepatocellular carcinoma after transcatheter arterial chemoembolization. Cancer. 2000;88:50–7.PubMedCrossRef
32.
go back to reference O’Suilleabhain CB, Poon RTP, Yong JL, Ooi GC, Tso WK, Fan ST. Factors predictive of 5-year survival after transarterial chemoembolization for inoperable hepatocellular carcinoma. Br J Surg. 2003;90:325–31.PubMedCrossRef O’Suilleabhain CB, Poon RTP, Yong JL, Ooi GC, Tso WK, Fan ST. Factors predictive of 5-year survival after transarterial chemoembolization for inoperable hepatocellular carcinoma. Br J Surg. 2003;90:325–31.PubMedCrossRef
Metadata
Title
Prognostic relevance of oncological serum biomarkers in liver cancer patients undergoing transarterial chemoembolization therapy
Authors
Nikolaus Kohles
Dorothea Nagel
Dietrich Jüngst
Jürgen Durner
Petra Stieber
Stefan Holdenrieder
Publication date
01-02-2012
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 1/2012
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-011-0237-7

Other articles of this Issue 1/2012

Tumor Biology 1/2012 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