High pre-treatment static and dynamic alpha-fetoprotein values predict reduced overall survival in hepatocellular carcinoma

Carolin Czauderna; Irene Schmidtmann; Sandra Koch; Lukas Pilz; Sophia Heinrich; Gerd Otto; Jens Mittler; Hauke Lang; Roman Kloeckner; Christoph Düber; Martin F. Sprinzl; Marcus A. Wörns; Peter R. Galle; Jens U. Marquardt; Arndt Weinmann

doi:10.1177/2050640620972611

High pre-treatment static and dynamic alpha-fetoprotein values predict reduced overall survival in hepatocellular carcinoma

Carolin Czauderna, Irene Schmidtmann, Sandra Koch, Lukas Pilz, Sophia Heinrich, Gerd Otto, Jens Mittler, Hauke Lang, Roman Kloeckner, Christoph Düber, Martin F. Sprinzl, Marcus A. Wörns, Peter R. Galle, Jens U. Marquardt^*, Arndt Weinmann

^*Corresponding author for this work

Clinic of Internal Medicine I

Johannes Gutenberg University Mainz

Abstract

Background: Hepatocellular carcinoma is one of the most lethal cancers worldwide. Novel prognostic and/or predictive biomarkers are urgently needed to improve patient management. Alpha-fetoprotein is a well-established and widely used biomarker for hepatocellular carcinoma. However, diagnostic accuracy of static alpha-fetoprotein values is limited and the clinical potential is a matter of ongoing scientific discussion. Objective: We here evaluated the prognostic impact of pre-treatment static and dynamic alpha-fetoprotein variables on overall survival of hepatocellular carcinoma patients in a Western cohort. Methods: Patients with confirmed hepatocellular carcinoma (n = 809) treated at the Johannes Gutenberg-University Mainz between 1998 and 2014 and two available pre-treatment alpha-fetoprotein-values (AFP-slope) were retrospectively analysed. Clinico-pathological baseline parameters, pre-treatment static values and AFP-slope were assessed. Prognostic impact was determined by Kaplan–Meier analyses and Cox regression models. Results: High static and dynamic alpha-fetoprotein variables prior to therapy were associated with reduced survival rates of hepatocellular carcinoma patients. Several known clinical parameters such as Child–Pugh B (p < 0.01) and C stage (p < 0.001), portal vein thrombosis (p < 0.001) and extrahepatic spread (p < 0.001) were confirmed as independent predictors for overall survival. Addition of static and/or dynamic alpha-fetoprotein variable resulted in higher time-dependent area under the curves. Notably, in patients with more favourable prognosis, AFP-slope prior to therapy was a slightly stronger predictor for overall survival compared with static alpha-fetoprotein values. Conclusion: Static and dynamic alpha-fetoprotein variables prior to therapy are predictive for overall survival of hepatocellular carcinoma patients. Addition of AFP-slope to established prognostic parameters might improve prognostic classification for a subgroup of hepatocellular carcinoma patients with preserved liver function and without portal vein tumour thrombosis.

Original language	English
Journal	United European Gastroenterology Journal
ISSN	2050-6406
DOIs	https://doi.org/10.1177/2050640620972611
Publication status	Published - 2020

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Czauderna, C., Schmidtmann, I., Koch, S., Pilz, L., Heinrich, S., Otto, G., Mittler, J., Lang, H., Kloeckner, R., Düber, C., Sprinzl, M. F., Wörns, M. A., Galle, P. R., Marquardt, J. U., & Weinmann, A. (2020). High pre-treatment static and dynamic alpha-fetoprotein values predict reduced overall survival in hepatocellular carcinoma. United European Gastroenterology Journal. https://doi.org/10.1177/2050640620972611

@article{dafbd6b6b48348cd8f4115b0c36c515a,

title = "High pre-treatment static and dynamic alpha-fetoprotein values predict reduced overall survival in hepatocellular carcinoma",

abstract = "Background: Hepatocellular carcinoma is one of the most lethal cancers worldwide. Novel prognostic and/or predictive biomarkers are urgently needed to improve patient management. Alpha-fetoprotein is a well-established and widely used biomarker for hepatocellular carcinoma. However, diagnostic accuracy of static alpha-fetoprotein values is limited and the clinical potential is a matter of ongoing scientific discussion. Objective: We here evaluated the prognostic impact of pre-treatment static and dynamic alpha-fetoprotein variables on overall survival of hepatocellular carcinoma patients in a Western cohort. Methods: Patients with confirmed hepatocellular carcinoma (n = 809) treated at the Johannes Gutenberg-University Mainz between 1998 and 2014 and two available pre-treatment alpha-fetoprotein-values (AFP-slope) were retrospectively analysed. Clinico-pathological baseline parameters, pre-treatment static values and AFP-slope were assessed. Prognostic impact was determined by Kaplan–Meier analyses and Cox regression models. Results: High static and dynamic alpha-fetoprotein variables prior to therapy were associated with reduced survival rates of hepatocellular carcinoma patients. Several known clinical parameters such as Child–Pugh B (p < 0.01) and C stage (p < 0.001), portal vein thrombosis (p < 0.001) and extrahepatic spread (p < 0.001) were confirmed as independent predictors for overall survival. Addition of static and/or dynamic alpha-fetoprotein variable resulted in higher time-dependent area under the curves. Notably, in patients with more favourable prognosis, AFP-slope prior to therapy was a slightly stronger predictor for overall survival compared with static alpha-fetoprotein values. Conclusion: Static and dynamic alpha-fetoprotein variables prior to therapy are predictive for overall survival of hepatocellular carcinoma patients. Addition of AFP-slope to established prognostic parameters might improve prognostic classification for a subgroup of hepatocellular carcinoma patients with preserved liver function and without portal vein tumour thrombosis.",

author = "Carolin Czauderna and Irene Schmidtmann and Sandra Koch and Lukas Pilz and Sophia Heinrich and Gerd Otto and Jens Mittler and Hauke Lang and Roman Kloeckner and Christoph D{\"u}ber and Sprinzl, {Martin F.} and W{\"o}rns, {Marcus A.} and Galle, {Peter R.} and Marquardt, {Jens U.} and Arndt Weinmann",

note = "Funding Information: JUM is supported by the Volkswagen Foundation (Lichtenberg Programm). CC is supported by a TransMed Fellowship of the University of Mainz. Aspects of this article are part of the doctoral thesis of LP. Author contribution: collection of data: CC, SK, LP, SH, GO, JM, HL, RK, CD, MFS, MAW, PRG, JUM, AW. Analysed the data: CC, IS, SK, LP, AW, JUM. Wrote the paper: CC, IS, JUM, A.W. All authors discussed the results and critically commented on the manuscript. All authors had access to the study data and reviewed and approved the final manuscript. Funding Information: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was supported by internal funding of the 1. Department of Medicine, University Medical Centre, University of Mainz, Germany. Publisher Copyright: {\textcopyright} Author(s) 2020. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

year = "2020",

doi = "10.1177/2050640620972611",

language = "English",

journal = "United European Gastroenterology Journal",

issn = "2050-6406",

}

Czauderna, C, Schmidtmann, I, Koch, S, Pilz, L, Heinrich, S, Otto, G, Mittler, J, Lang, H, Kloeckner, R, Düber, C, Sprinzl, MF, Wörns, MA, Galle, PR, Marquardt, JU & Weinmann, A 2020, 'High pre-treatment static and dynamic alpha-fetoprotein values predict reduced overall survival in hepatocellular carcinoma', United European Gastroenterology Journal. https://doi.org/10.1177/2050640620972611

TY - JOUR

T1 - High pre-treatment static and dynamic alpha-fetoprotein values predict reduced overall survival in hepatocellular carcinoma

AU - Czauderna, Carolin

AU - Schmidtmann, Irene

AU - Koch, Sandra

AU - Pilz, Lukas

AU - Heinrich, Sophia

AU - Otto, Gerd

AU - Mittler, Jens

AU - Lang, Hauke

AU - Kloeckner, Roman

AU - Düber, Christoph

AU - Sprinzl, Martin F.

AU - Wörns, Marcus A.

AU - Galle, Peter R.

AU - Marquardt, Jens U.

AU - Weinmann, Arndt

N1 - Funding Information: JUM is supported by the Volkswagen Foundation (Lichtenberg Programm). CC is supported by a TransMed Fellowship of the University of Mainz. Aspects of this article are part of the doctoral thesis of LP. Author contribution: collection of data: CC, SK, LP, SH, GO, JM, HL, RK, CD, MFS, MAW, PRG, JUM, AW. Analysed the data: CC, IS, SK, LP, AW, JUM. Wrote the paper: CC, IS, JUM, A.W. All authors discussed the results and critically commented on the manuscript. All authors had access to the study data and reviewed and approved the final manuscript. Funding Information: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was supported by internal funding of the 1. Department of Medicine, University Medical Centre, University of Mainz, Germany. Publisher Copyright: © Author(s) 2020. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020

Y1 - 2020

N2 - Background: Hepatocellular carcinoma is one of the most lethal cancers worldwide. Novel prognostic and/or predictive biomarkers are urgently needed to improve patient management. Alpha-fetoprotein is a well-established and widely used biomarker for hepatocellular carcinoma. However, diagnostic accuracy of static alpha-fetoprotein values is limited and the clinical potential is a matter of ongoing scientific discussion. Objective: We here evaluated the prognostic impact of pre-treatment static and dynamic alpha-fetoprotein variables on overall survival of hepatocellular carcinoma patients in a Western cohort. Methods: Patients with confirmed hepatocellular carcinoma (n = 809) treated at the Johannes Gutenberg-University Mainz between 1998 and 2014 and two available pre-treatment alpha-fetoprotein-values (AFP-slope) were retrospectively analysed. Clinico-pathological baseline parameters, pre-treatment static values and AFP-slope were assessed. Prognostic impact was determined by Kaplan–Meier analyses and Cox regression models. Results: High static and dynamic alpha-fetoprotein variables prior to therapy were associated with reduced survival rates of hepatocellular carcinoma patients. Several known clinical parameters such as Child–Pugh B (p < 0.01) and C stage (p < 0.001), portal vein thrombosis (p < 0.001) and extrahepatic spread (p < 0.001) were confirmed as independent predictors for overall survival. Addition of static and/or dynamic alpha-fetoprotein variable resulted in higher time-dependent area under the curves. Notably, in patients with more favourable prognosis, AFP-slope prior to therapy was a slightly stronger predictor for overall survival compared with static alpha-fetoprotein values. Conclusion: Static and dynamic alpha-fetoprotein variables prior to therapy are predictive for overall survival of hepatocellular carcinoma patients. Addition of AFP-slope to established prognostic parameters might improve prognostic classification for a subgroup of hepatocellular carcinoma patients with preserved liver function and without portal vein tumour thrombosis.

AB - Background: Hepatocellular carcinoma is one of the most lethal cancers worldwide. Novel prognostic and/or predictive biomarkers are urgently needed to improve patient management. Alpha-fetoprotein is a well-established and widely used biomarker for hepatocellular carcinoma. However, diagnostic accuracy of static alpha-fetoprotein values is limited and the clinical potential is a matter of ongoing scientific discussion. Objective: We here evaluated the prognostic impact of pre-treatment static and dynamic alpha-fetoprotein variables on overall survival of hepatocellular carcinoma patients in a Western cohort. Methods: Patients with confirmed hepatocellular carcinoma (n = 809) treated at the Johannes Gutenberg-University Mainz between 1998 and 2014 and two available pre-treatment alpha-fetoprotein-values (AFP-slope) were retrospectively analysed. Clinico-pathological baseline parameters, pre-treatment static values and AFP-slope were assessed. Prognostic impact was determined by Kaplan–Meier analyses and Cox regression models. Results: High static and dynamic alpha-fetoprotein variables prior to therapy were associated with reduced survival rates of hepatocellular carcinoma patients. Several known clinical parameters such as Child–Pugh B (p < 0.01) and C stage (p < 0.001), portal vein thrombosis (p < 0.001) and extrahepatic spread (p < 0.001) were confirmed as independent predictors for overall survival. Addition of static and/or dynamic alpha-fetoprotein variable resulted in higher time-dependent area under the curves. Notably, in patients with more favourable prognosis, AFP-slope prior to therapy was a slightly stronger predictor for overall survival compared with static alpha-fetoprotein values. Conclusion: Static and dynamic alpha-fetoprotein variables prior to therapy are predictive for overall survival of hepatocellular carcinoma patients. Addition of AFP-slope to established prognostic parameters might improve prognostic classification for a subgroup of hepatocellular carcinoma patients with preserved liver function and without portal vein tumour thrombosis.

UR - http://www.scopus.com/inward/record.url?scp=85096463896&partnerID=8YFLogxK

U2 - 10.1177/2050640620972611

DO - 10.1177/2050640620972611

M3 - Journal articles

AN - SCOPUS:85096463896

SN - 2050-6406

JO - United European Gastroenterology Journal

JF - United European Gastroenterology Journal

ER -

High pre-treatment static and dynamic alpha-fetoprotein values predict reduced overall survival in hepatocellular carcinoma

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