Model combining pre-transplant tumor biomarkers and tumor size shows more utility in predicting hepatocellular carcinoma recurrence and survival than the BALAD models

Nicha Wongjarupong, Gabriela M. Negron-Ocasio, Roongruedee Chaiteerakij, Benyam D. Addissie, Essa A. Mohamed, Kristin C. Mara, William S. Harmsen, J. Paul Theobald, Brian E. Peters, Joseph G. Balsanek, Melissa M. Ward, Nasra H. Giama, Sudhakar K Venkatesh, Denise Harnois, Michael R. Charlton, Hiroyuki Yamada, Alicia Algeciras-Schimnich, Melissa R. Snyder, Terry M Therneau, Lewis Rowland Roberts

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3 Scopus citations

Abstract

AIM To assess the performance of BALAD, BALAD-2 and their component biomarkers in predicting outcome of hepatocellular carcinoma (HCC) patients after liver transplant. METHODS BALAD score and BALAD-2 class are derived from bilirubin, albumin, alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive AFP (AFP-L3), and des-gamma-carboxyprothrombin (DCP). Pre-transplant AFP, AFP-L3 and DCP were measured in 113 patients transplanted for HCC from 2000 to 2008. Hazard ratios (HR) for recurrence and death were calculated. Univariate and multivariate regression analyses were conducted. C-statistics were used to compare biomarker-based to predictive models. RESULTS During a median follow-up of 12.2 years, 38 patients recurred and 87 died. The HRs for recurrence in patients with elevated AFP, AFP-L3, and DCP defined by BALAD cut-off values were 2.42 (1.18-5.00), 1.86 (0.98-3.52), and 2.83 (1.42-5.61), respectively. For BALAD, the HRs for recurrence and death per unit increased score were 1.48 (1.15-1.91) and 1.59 (1.28-1.97). For BALAD-2, the HRs for recurrence and death per unit increased class were 1.45 (1.06-1.98) and 1.38 (1.09-1.76). For recurrence prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs. 0.64, 0.61, 0.53, and 0.53 for BALAD, BALAD-2, Milan, and UCSF, respectively. Similarly, for death prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs 0.65, 0.61, 0.52, and 0.50 for BALAD, BALAD-2, Milan, and UCSF. A new model combining biomarkers with tumor size at the time of transplant (S-LAD) demonstrated the highest predictive capability with c-statistics of 0.71 and 0.69 for recurrence and death. CONCLUSION BALAD and BALAD-2 are valid in transplant HCC patients, but less predictive than the three biomarkers in combination or the three biomarkers in combination with maximal tumor diameter (S-LAD).

Original languageEnglish (US)
Pages (from-to)1321-1331
Number of pages11
JournalWorld Journal of Gastroenterology
Volume24
Issue number12
DOIs
StatePublished - Mar 28 2018

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Keywords

  • AFP-L3
  • Alpha-fetoprotein
  • BALAD
  • BALAD-2
  • Des-gamma-carboxyprothrombin
  • Hepatocellular carcinoma
  • Liver transplant
  • Outcome
  • Recurrence

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Wongjarupong, N., Negron-Ocasio, G. M., Chaiteerakij, R., Addissie, B. D., Mohamed, E. A., Mara, K. C., Harmsen, W. S., Theobald, J. P., Peters, B. E., Balsanek, J. G., Ward, M. M., Giama, N. H., Venkatesh, S. K., Harnois, D., Charlton, M. R., Yamada, H., Algeciras-Schimnich, A., Snyder, M. R., Therneau, T. M., & Roberts, L. R. (2018). Model combining pre-transplant tumor biomarkers and tumor size shows more utility in predicting hepatocellular carcinoma recurrence and survival than the BALAD models. World Journal of Gastroenterology, 24(12), 1321-1331. https://doi.org/10.3748/wjg.v24.i12.1321