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Br J Cancer. 2014 Apr 15;110(8):2090-8. doi: 10.1038/bjc.2014.130. Epub 2014 Apr 1.

Biomarker-based prognosis in hepatocellular carcinoma: validation and extension of the BALAD model.

Author information

1
Cancer Research UK Clinical Trials Unit, School of Cancer Sciences, University of Birmingham, Birmingham B15 2TT, UK.
2
Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L69 3GA, UK.
3
Department of Oncology, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 0QQ, UK.
4
Liverpool Cancer Research UK Centre, Liverpool Cancer Trials Unit, University of Liverpool, Liverpool L69 3GL, UK.
5
Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Gifu 503-8052, Japan.
6
Wako Life Sciences, Inc., Mountain View, CA 94043-1829, USA.
7
1] Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L69 3GA, UK [2] The Clatterbridge Cancer Centre NHS Foundation Trust, Clatterbridge Road, Bebington, Wirral CH63 4JY, UK.

Abstract

BACKGROUND:

The Japanese 'BALAD' model offers the first objective, biomarker-based, tool for assessment of prognosis in hepatocellular carcinoma, but relies on dichotomisation of the constituent data, has not been externally validated, and cannot be applied to the individual patients.

METHODS:

In this Japanese/UK collaboration, we replicated the original BALAD model on a UK cohort and then built a new model, BALAD-2, on the original raw Japanese data using variables in their continuous form. Regression analyses using flexible parametric models with fractional polynomials enabled fitting of appropriate baseline hazard functions and functional form of covariates. The resulting models were validated in the respective cohorts to measure the predictive performance.

RESULTS:

The key prognostic features were confirmed to be Bilirubin and Albumin together with the serological cancer biomarkers, AFP-L3, AFP, and DCP. With appropriate recalibration, the model offered clinically relevant discrimination of prognosis in both the Japanese and UK data sets and accurately predicted patient-level survival.

CONCLUSIONS:

The original BALAD model has been validated in an international setting. The refined BALAD-2 model permits estimation of patient-level survival in UK and Japanese cohorts.

PMID:
24691419
PMCID:
PMC3992496
DOI:
10.1038/bjc.2014.130
[Indexed for MEDLINE]
Free PMC Article

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