title: Biomarker-based prognosis in hepatocellular carcinoma: validation and extension of the BALAD model.
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.
authors.affiliation: Cancer Research UK Clinical Trials Unit, School of Cancer Sciences, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: R
authors.initials: R
authors.lastname: Fox
authors.affiliation: Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L69 3GA, UK.
authors.forename: S
authors.initials: S
authors.lastname: Berhane
authors.affiliation: Department of Oncology, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 0QQ, UK.
authors.forename: M
authors.initials: M
authors.lastname: Teng
authors.affiliation: Liverpool Cancer Research UK Centre, Liverpool Cancer Trials Unit, University of Liverpool, Liverpool L69 3GL, UK.
authors.forename: T
authors.initials: T
authors.lastname: Cox
authors.affiliation: Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Gifu 503-8052, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tada
authors.affiliation: Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Gifu 503-8052, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Toyoda
authors.affiliation: Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Gifu 503-8052, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kumada
authors.affiliation: Wako Life Sciences, Inc., Mountain View, CA 94043-1829, USA.
authors.forename: C
authors.initials: C
authors.lastname: Kagebayashi
authors.affiliation: Wako Life Sciences, Inc., Mountain View, CA 94043-1829, USA.
authors.forename: S
authors.initials: S
authors.lastname: Satomura
authors.affiliation: 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.
authors.forename: P J
authors.initials: PJ
authors.lastname: Johnson
mesh_terms: D000368:Aged; D001663:Bilirubin / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000235:genetics / Q000473:pathology; D005260:Female; D006801:Humans; D007564:Japan; D008113:Liver Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011498:Protein Precursors / Q000097:blood; D011516:Prothrombin; D012709:Serum Albumin / Q000378:metabolism; D006113:United Kingdom; D000509:alpha-Fetoproteins / Q000378:metabolism*
chemical_list: C097353:AFP protein, human; D015415:Biomarkers; D014408:Biomarkers, Tumor; D011498:Protein Precursors; D012709:Serum Albumin; D000509:alpha-Fetoproteins; C008208:acarboxyprothrombin; D011516:Prothrombin; D001663:Bilirubin