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

Abstract

AIMTo assess the performance of BALAD, BALAD-2 and their component biomarkers in predicting outcome of hepatocellular carcinoma (HCC) patients after liver transplant.METHODSBALAD 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.RESULTSDuring 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.CONCLUSIONBALAD 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).

Validation of novel Japanese indication criteria and biomarkers among living donor liver transplantation recipients with hepatocellular carcinoma - a single center retrospective study

“…AFP-L3, a reliable marker for the diagnosis of HCC [20] , proved to be a promising marker for recurrence after LT since the specificity of AFP-L3 was the highest [ Figure 2] and patient recurrence rate curves were well stratified using AFP-L3 [ Supplementary Figure 2]. However, there has been little study [34] investigating the usefulness of AFP-L3 in predicting HCC recurrence after LT. Highly sensitive AFP-L3 became available around 2010 in Japan, which enabled the measurement of AFP-L3 even in patients with total AFP levels below 20 ng/mL [20,[35][36][37] .…”

Evaluation of Lens culinaris agglutinin-reactive α-fetoprotein for diagnosis of malignant tumors

“…Some scholars thought that AFP-L3 measurement was allowed to predict the potential of biological malignancy of HCC prior to any therapy. To be noted, the AFP-L3 was also believed to contribute to the prediction of HCC relapse post curative therapy much earlier compared to the AFP detection (25)(26)(27)(28).…”

Current Status Regarding Tumour Progression, Surveillance, Diagnosis, Staging, and Treatment Of HCC: A Literature Review

“…In addition, the BALAD score is another model that can be used for surveillance, prediction of the survival, and recurrence of HCC. BALAD consists of 5 serum biomarkers, the Bilirubin and Albumin is used to assess the remnant liver function, while the other three biomarkers related to serum tumor biomarkers are: AFP, Des-Gamma-Carboxy Prothrombin (DCP), and Lens culinaris agglutininreactive AFP (AFP-L3) [40] . AFP is considered as an oncofetal protein also known as alpha-fetoglobulin.…”

“…Only a small percentage (10-20%) of early tumor stage can be detected by increasing AFP serum levels. Also, AFP is considered as a widely HCC biomarker proposed for prediction of HCC recurrence [40,41] it is necessary to establish a comprehensive panel of HCC biomarkers related to tumour behaviour and cancer prognosis. Resected HCCs from 251 patients were stained for hepatic progenitor cell (HPC).…”