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 M. Harnois, Michael R. Charlton, Hiroyuki Yamada, Alicia Algeciras-Schimnich, Melissa R. Snyder, Terry M. Therneau, Lewis R. Roberts

Research output: Contribution to journalReview articlepeer-review

7 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

Bibliographical note

Funding Information:
funding from BTG, Gilead Sciences and Wako Life Sciences; Yamada H is an employee of Wako Life Sciences. There are no

Funding Information:
Supported by Mayo Clinic Center for Clinical and Translational Science (CCATS), No. NCATS 1UL1TR002377-01; Mayo Clinic Center for Cell Signaling in Gastroenterology, No. NIDDK P30DK084567-09; and Wako Life Sciences, Inc.

Publisher Copyright:
© The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.

Keywords

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

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