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Baseline Alpha-Fetoprotein, Alpha-Fetoprotein-L3, and Des-Gamma-Carboxy Prothrombin Biomarker Status in Bridge to Liver Transplant Outcomes for Hepatocellular Carcinoma.

ABSTRACT: The biomarkers α-fetoprotein (AFP), Lens culinaris agglutinin-reactive AFP fraction (AFP-L3), and des-γ-carboxy prothrombin (DCP) have emerging implications in hepatocellular carcinoma (HCC) surveillance, overall prognosis, and post-surgical recurrence risk. This retrospective study investigated treatment and bridge to liver transplant (LT) prognosis associated with AFP, AFP-L3%, and DCP biomarker profiles prior to liver-directed therapy (LDT). In a 140-patient cohort, each biomarker was associated with HCC progression risk using the established thresholds of AFP > 20 ng/mL, AFP-L3 > 15%, and DCP > 7.5 ng/mL. Over 60% of the cohort expressed at least one biomarker at baseline. Although most biomarker-positive patients expressed the clinical standard AFP (57/87), only 32% were positive for AFP alone. Biomarker accumulation increased HCC progression risk but was not associated with demographic factors or preserved liver function. Biomarker triple negative patients had smaller index HCC (p = 0.003), decreased multifocal burden (p = 0.010), and a higher objective response rate (ORR, 62% compared to 46%, p = 0.011). Expressing all three biomarkers at baseline was associated with dismal first-line ORR (12%) with a median time to progression (TTP) of only 181 days post-LDT. Patients with triple negative status for the HCC biomarkers AFP, AFP-L3%, and DCP have the highest first-line ORR with < 5% HCC progression 1-year post-LDT. Biomarker profiling can establish baseline prognosis for identifying optimal bridge to LT and downstaging to LT candidates with triple negative biomarker status and providing an ideal post-LDT target as a compliment to radiographic response.

SUBMITTER: Nunez KG

PROVIDER: S-EPMC8507524 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThere is increasing interest in transplanting patients with hepatocellular carcinoma (HCC) with tumors greater than 5 cm (Milan criteria).AimTo investigate possible prognostically-useful factors for liver transplantation in HCC patients with large tumors.MethodsIn this clinical study, 50 patients with HCC who were transplanted at our Liver Transplant Center between April 2006 and August 2019 and had tumors greater than 6 cm maximum diameter were retrospectively analyzed. Their survival and full clinical characteristics were examined, with respect to serum alpha-fetoprotein (AFP) and gamma glutamyl transpeptidase (GGT) levels. Kaplan-Meier survival estimates were used to determine overall survival and disease-free survival in these patients. The inclusion criterion was evidence of HCC. Exclusion criteria were the presence of macroscopic portal vein thrombosis or metastasis and a follow-up period of less than 90 d.ResultsUsing receiver operating characteristic curve (ROC) analysis, cutoff values of AFP 200 ng/mL and GGT 104 IU/L were identified and used in this study. Significantly longer overall survival (OS) and disease-free-survival (DFS) were found in patients who had lower values of either parameter, compared with higher values. Even greater differences in survival were found when the 2 parameters were combined. Two tumor size bands were identified, in searching for the limits of this approach with larger tumors, namely 6-10 cm and > 10 cm. Combination parameters in the 6-10 cm band reflected 5-year OS of 76.2% in patients with low AFP plus low GGT vs 0% for all other groups. Patients with tumors greater than 10 cm, did not have low AFP plus low GGT. The most consistent clinical correlates for longer survival were degree of tumor differentiation and absence of microscopic portal venous invasion.ConclusionSerum levels of AFP and GGT, both alone and combined, represent a simple prognostic identifier in patients with large HCCs undergoing liver transplant-ation.

Dataset Information

Baseline Alpha-Fetoprotein, Alpha-Fetoprotein-L3, and Des-Gamma-Carboxy Prothrombin Biomarker Status in Bridge to Liver Transplant Outcomes for Hepatocellular Carcinoma.

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