Albumin-to-Alkaline Phosphatase Ratio as an Independent Prognostic Factor for Overall Survival of Advanced Hepatocellular Carcinoma Patients without Receiving Standard Anti-Cancer Therapies

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Abstract

Background Albumin-to-Alkaline Phosphatase Ratio (ALB/ALP ratio, AAPR), a newly developed index of liver function, has been rarely discussed about its prognostic value in malignancies. The current study attempted to evaluate the prognostic prediction of AAPR in advanced HCC.

Methods 237 advanced HCC patients who refused any standard anti-cancer therapies were retrospectively analyzed. The threshold value of AAPR was determined by receiver operating characteristic (ROC) curve. Univariate analyses using Kaplan-Meier method and log-rank test, and multivariate analysis using Cox proportional hazards regression model were conducted. Comparisons of ROC curves and likelihood ratio test (LRT) were utilized to compare the value of different factors in predicting survival.

Results ROC curve analysis confirmed 0.38 as the optimal cutoff value of AAPR in evaluating overall survival (OS). Patients with an AAPR > 0.38 exhibited significantly lower frequencies of ascites, portal vein tumor thrombus, Child-Pugh grade B & C, and KPS < 70 (all P < 0.05). These patients also displayed a longer median survival time than those with an AAPR ≤ 0.38 (5.8 m vs 2.4 m, P < 0.01). Univariate and multivariate analyses identified AAPR as an independent prognostic indicator ( HR = 0.592, P = 0.007). Furthermore, we integrated AAPR with TNM system and found that area under curve of AAPR-TNM system was significantly larger than that of TNM system when predicting 3-month survival (0.670 vs 0.611, P < 0.01). Moreover, LRT indicated that AAPR-TNM system had a significantly larger χ ² (26.4 vs 16.4, P < 0.01) and a significantly smaller Akaike information criterion value (1936 vs 1948, P < 0.01) comparing with TNM system.

Conclusions Our study implied that AAPR was a potentially valuable prognostic index for advanced HCC patients without receiving any standard anti-cancer therapies. AAPR-TNM system preceded TNM system in predicting overall survival in this study.

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Most cited references 17

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Management of hepatocellular carcinoma.

Jordi Bruix, Morris Sherman (2005)

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Estimation of the Youden Index and its associated cutoff point.

Ronen Fluss, David Faraggi, Benjamin Reiser (2005)

The Youden Index is a frequently used summary measure of the ROC (Receiver Operating Characteristic) curve. It both, measures the effectiveness of a diagnostic marker and enables the selection of an optimal threshold value (cutoff point) for the marker. In this paper we compare several estimation procedures for the Youden Index and its associated cutoff point. These are based on (1) normal assumptions; (2) transformations to normality; (3) the empirical distribution function; (4) kernel smoothing. These are compared in terms of bias and root mean square error in a large variety of scenarios by means of an extensive simulation study. We find that the empirical method which is the most commonly used has the overall worst performance. In the estimation of the Youden Index the kernel is generally the best unless the data can be well transformed to achieve normality whereas in estimation of the optimal threshold value results are more variable.

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Construction of the Chinese University Prognostic Index for hepatocellular carcinoma and comparison with the TNM staging system, the Okuda staging system, and the Cancer of the Liver Italian Program staging system: a study based on 926 patients.

Benny Zee, Hans J. Johnson, Janet Y M Tang … (2002)

The current TNM staging system for patients with hepatocellular carcinoma (HCC) does not include liver function parameters and does not provide a precise prognosis for patients in different risk groups. The objectives of this study were to construct a new prognostic index for patients with hepatocellular carcinoma, the Chinese University Prognostic Index (CUPI), and to compare it with existing staging systems in terms of their ability to classify patients into different risk group. From 1996 to 1998, 926 ethnic Chinese patients who were diagnosed with HCC (mainly hepatitis B-associated) at a single institution were recruited prospectively into this study. A multivariate analysis on 19 patient characteristics was performed using a Cox regression model to identify independent prognostic factors. Weights were derived from the regression coefficients of various factors to construct the CUPI. Patients were classified according to different staging systems. Survival curves were plotted with the Kaplan-Meier method and were compared by using a log-rank test. Both the TNM staging system and the Okuda staging system had prognostic significance, but the significance was lower for the Cancer of the Liver Italian Program (CLIP) prognostic score among the patients in the study population. The CUPI was constructed by adding the following factors into the TNM staging system: total bilirubin, ascites, alkaline phosphatase, alpha fetoprotein, and asymptomatic disease on presentation. The new CUPI characterized three risk groups with highly significant differences in survival during the whole period of follow-up (P < 0.00001) and was more discriminant than the other systems. In the study population of patients with mainly hepatitis B-associated HCC, the CUPI was more discriminant than the TNM staging system, the Okuda staging systems, or the CLIP prognostic score in classifying patients into different risk groups and was better at predicting survival. The CUPI needs to be validated by different cohorts of patients before it can be recommended for general use. Copyright 2002 American Cancer Society.

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Author and article information

Journal

Journal ID (nlm-ta): J Cancer

Journal ID (iso-abbrev): J Cancer

Journal ID (publisher-id): jca

Title: Journal of Cancer

Publisher: Ivyspring International Publisher (Sydney )

ISSN (Electronic): 1837-9664

Publication date Collection: 2018

Publication date (Electronic): 1 January 2018

Volume: 9

Issue: 1

Pages: 189-197

Affiliations

[1 ]Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease, the Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, People's Republic of China;

[2 ]Department of Medical Oncology of Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfengdong Road, Guangzhou, 510060, People's Republic of China;

[3 ]Department of Intervention and Radiology, Guangdong Key Laboratory of Liver Disease, the Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, People's Republic of China.

Author notes

✉ Corresponding authors: Zhanhong Chen: Address: Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease, the Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, People's Republic of China; Tel: +86-20-85252212; E-mail: chzhanh3@ 123456mail.sysu.edu.cn Xiangyuan Wu: Address: Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease, the Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, People's Republic of China; Tel: +86-20-85252212; E-mail: wuxiangy@ 123456mail.sysu.edu.cn

* These authors contributed equally to this work

Competing Interests: The authors of this study have no disclosures regarding funding or any conflict of interest with respect to this manuscript. The authors have not received fees for serving as speakers for any organization, and have not received research funding from any organization. The authors are not employees of any organization and do not own stocks and/or shares in any organization. The authors do not own patents.

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Publisher ID: jcav09p0189

DOI: 10.7150/jca.21799

PMC ID: 5743727

PubMed ID: 29290785

SO-VID: c0c0e17f-114b-4f8d-9473-a5686b2fcae1

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This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.

Albumin-to-Alkaline Phosphatase Ratio as an Independent Prognostic Factor for Overall Survival of Advanced Hepatocellular Carcinoma Patients without Receiving Standard Anti-Cancer Therapies

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Karger: Oncology

Most cited references 17

Management of hepatocellular carcinoma.

Estimation of the Youden Index and its associated cutoff point.

Construction of the Chinese University Prognostic Index for hepatocellular carcinoma and comparison with the TNM staging system, the Okuda staging system, and the Cancer of the Liver Italian Program staging system: a study based on 926 patients.

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