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      Albumin-to-Alkaline Phosphatase Ratio: A Novel Prognostic Index for Hepatocellular Carcinoma

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          Abstract

          Prognosis of patients with hepatocellular carcinoma (HCC) depends on both tumour extent and hepatic function reserve. Liver function test (LFT) is a basic routine blood test to evaluate hepatic function. We first analysed LFT components and their associated scores in a training cohort of 217 patients who underwent curative surgery to identify LFT parameters with high performance (discriminatory capacity, homogeneity, and monotonicity of gradient). We derived a novel index, albumin-to-alkaline phosphatase ratio (AAPR), which had the highest c-index (0.646) and χ 2 (24.774) among other liver biochemical parameters. The AAPR was an independent prognostic factor for overall and disease-free survival. The adjusted hazard ratio of death and tumour relapse was 2.36 ( P = 0.002) and 1.85 ( P = 0.010), respectively. The independent prognostic significance of AAPR on top of 5 commonly used and well established staging systems was further confirmed in 2 independent cohorts of patients receiving surgical resection ( n = 256) and palliative therapy ( n = 425). In summary, the AAPR is a novel index readily derived from a simple low-cost routine blood test and is an independent prognostic indicator for patients with HCC regardless of treatment options.

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          Advanced hepatocellular carcinoma: which staging systems best predict prognosis?

          Fidel-David Huitzil-Melendez, Marinela Capanu, Eileen M O'Reilly … (2010)
          The purpose of cancer staging systems is to accurately predict patient prognosis. The outcome of advanced hepatocellular carcinoma (HCC) depends on both the cancer stage and the extent of liver dysfunction. Many staging systems that include both aspects have been developed. It remains unknown, however, which of these systems is optimal for predicting patient survival. Patients with advanced HCC treated over a 5-year period at Memorial Sloan-Kettering Cancer Center were identified from an electronic medical record database. Patients with sufficient data for utilization in all staging systems were included. TNM sixth edition, Okuda, Barcelona Clinic Liver Cancer (BCLC), Cancer of the Liver Italian Program (CLIP), Chinese University Prognostic Index (CUPI), Japan Integrated Staging (JIS), and Groupe d'Etude et de Traitement du Carcinome Hepatocellulaire (GETCH) systems were ranked on the basis of their accuracy at predicting survival by using concordance index (c-index). Other independent prognostic variables were also identified. Overall, 187 eligible patients were identified and were staged by using the seven staging systems. CLIP, CUPI, and GETCH were the three top-ranking staging systems. BCLC and TNM sixth edition lacked any meaningful prognostic discrimination. Performance status, AST, abdominal pain, and esophageal varices improved the discriminatory ability of CLIP. In our selected patient population, CLIP, CUPI, and GETCH were the most informative staging systems in predicting survival in patients with advanced HCC. Prospective validation is required to determine if they can be accurately used to stratify patients in clinical trials and to direct the appropriate need for systemic therapy versus best supportive care. BCLC and TNM sixth edition were not helpful in predicting survival outcome, and their use is not supported by our data.
          Article 0 comments Cited 149 times – based on 0 reviews     Review now
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            Validation of a new prognostic staging system for hepatocellular carcinoma: the JIS score compared with the CLIP score.

            Seiji Haji, Yukio Osaki, Yo Sasaki … (2004)
            The Japan Integrated Staging score (JIS score), which combines the Child-Turcotte-Pugh classification and tumor-node-metastasis staging, has been proposed as a better prognostic staging system for hepatocellular carcinoma (HCC) than the Cancer of the Liver Italian Program (CLIP) scoring system. In this study, validation was performed among a larger patient population. A total of 4,525 consecutive patients with HCC who had been diagnosed at five institutions were included. Stratification ability, prognostic predictive power, and reproducibility were analyzed and compared with results from the CLIP scoring system. Only 45% (1,951 of 4,525) of all patients were categorized as early stage HCC according to JIS score (0 or 1), whereas 63% (2,878 of 4,525) of the patients were categorized as having a CLIP score of 0 or 1. Significant differences in survival curves were not observed among CLIP scores 3 to 6. In contrast, survival curves showed significant differences among all the JIS scores. The same JIS scoring subgroups showed a similar prognosis, and good internal reproducibility was observed in each of the institutions. Multivariate analysis of the prognosis in all 4,525 patients proved the JIS score to be the best prognostic factor. Furthermore, the Akaike information criteria proved that the JIS scoring system was statistically a better model for predicting outcome than the CLIP scoring system. In conclusion, the stratification ability and prognostic predictive power of the JIS score were much better than that of the CLIP score and were simple to obtain and remember.
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              New utility of an old marker: serial alpha-fetoprotein measurement in predicting radiologic response and survival of patients with hepatocellular carcinoma undergoing systemic chemotherapy.

              Winnie Yeo, Dave E. Johnson, Elliot E. Hui … (2009)
              There are limitations in using radiologic evaluation to assess the treatment outcome of patients with hepatocellular carcinoma (HCC). The use of serial alpha-fetoprotein (AFP) in monitoring response has not been rigorously evaluated. We aimed to study the clinical value of AFP trend in an attempt to validate AFP as a surrogate serologic end point. Participants from a phase III randomized trial of systemic chemotherapy in HCC were studied. Serum AFP was prospectively collected in parallel with clinical and radiologic outcome. AFP response was defined as a decrease in AFP of more than 20% after a minimum of two cycles of chemotherapy. We studied the relationship between AFP response and treatment outcome in terms of radiologic response and overall survival. Of 188 patients, 117 patients with elevated serum AFP (> 20 microg/L) and documented radiologic evaluation had received at least two cycles of chemotherapy. A total of 47 AFP responders were identified. AFP responders had better survival than nonresponders (13.5 v 5.6 months, respectively; P < .0001), and AFP response was strongly associated with radiologic response (P < .0001). Multivariate analysis suggested that AFP response was significantly associated with survival (hazard ratio, 0.413; 95% CI, 0.273 to 0.626; P < .0001). AFP responses were frequently observed in patients with radiologically stable disease (SD) and tended to identify a subgroup of SD patients with better survival. Serial AFP measurement is useful in prognostication and monitoring treatment response in HCC patients undergoing systemic chemotherapy. Incorporation of AFP response into the criteria evaluating treatment outcome should be considered in clinical practice and clinical trials of novel agents in HCC.
              Article 0 comments Cited 79 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Dis Markers
                Journal ID (iso-abbrev): Dis. Markers
                Journal ID (publisher-id): DM
                Title: Disease Markers
                Publisher: Hindawi Publishing Corporation
                ISSN (Print): 0278-0240
                ISSN (Electronic): 1875-8630
                Publication date (Print): 2015
                Publication date (Electronic): 9 February 2015
                Volume: 2015
                Electronic Location Identifier: 564057
                Affiliations
                1Department of Anatomical and Cellular Pathology, State Key Laboratory in Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong
                2Department of Clinical Oncology, State Key Laboratory in Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong
                3Institute of Digestive Disease, Partner State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
                4Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
                5Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong
                6Li Ka Shing Institute of Health Science, Sir Y. K. Pao Cancer Centre, The Chinese University of Hong Kong, Shatin, Hong Kong
                Author notes

                Academic Editor: Stamatios Theocharis

                Author information
                http://orcid.org/0000-0001-5807-7447
                Article
                DOI: 10.1155/2015/564057
                PMC ID: 4337043
                PubMed ID: 25737613
                SO-VID: aab77e2f-9e50-46b2-8826-e18b01f06396
                Copyright © Copyright © 2015 Anthony W. H. Chan et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 5 January 2015
                Date revision received : 27 January 2015
                Date accepted : 27 January 2015
                Categories
                Subject: Research Article

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