Baseline Alpha-Fetoprotein, Alpha-Fetoprotein-L3, and Des-Gamma-Carboxy Prothrombin Biomarker Status in Bridge to Liver Transplant Outcomes for Hepatocellular Carcinoma
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 tre...
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| Format: | Article |
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MDPI AG
2021-09-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/19/4765 |
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| author | Kelley G. Núñez Tyler Sandow Daniel Fort Jai Patel Mina Hibino Ian Carmody Ari J. Cohen Paul Thevenot |
| author_facet | Kelley G. Núñez Tyler Sandow Daniel Fort Jai Patel Mina Hibino Ian Carmody Ari J. Cohen Paul Thevenot |
| author_sort | Kelley G. Núñez |
| collection | DOAJ |
| description | 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 (<i>p</i> = 0.003), decreased multifocal burden (<i>p</i> = 0.010), and a higher objective response rate (ORR, 62% compared to 46%, <i>p</i> = 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. |
| first_indexed | 2024-03-10T07:05:39Z |
| format | Article |
| id | doaj.art-4bc00c8639344ef0b0c7a6b4f41ae334 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T07:05:39Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-4bc00c8639344ef0b0c7a6b4f41ae3342023-11-22T15:52:02ZengMDPI AGCancers2072-66942021-09-011319476510.3390/cancers13194765Baseline Alpha-Fetoprotein, Alpha-Fetoprotein-L3, and Des-Gamma-Carboxy Prothrombin Biomarker Status in Bridge to Liver Transplant Outcomes for Hepatocellular CarcinomaKelley G. Núñez0Tyler Sandow1Daniel Fort2Jai Patel3Mina Hibino4Ian Carmody5Ari J. Cohen6Paul Thevenot7Institute of Translational Research, Ochsner Health, New Orleans, LA 70121, USADepartment of Radiology, Ochsner Health, New Orleans, LA 70121, USACenter for Outcomes and Health Services Research, Ochsner Health, New Orleans, LA 70121, USAInstitute of Translational Research, Ochsner Health, New Orleans, LA 70121, USAInstitute of Translational Research, Ochsner Health, New Orleans, LA 70121, USAMulti-Organ Transplant Institute, Ochsner Health, New Orleans, LA 70121, USAInstitute of Translational Research, Ochsner Health, New Orleans, LA 70121, USAInstitute of Translational Research, Ochsner Health, New Orleans, LA 70121, USAThe 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 (<i>p</i> = 0.003), decreased multifocal burden (<i>p</i> = 0.010), and a higher objective response rate (ORR, 62% compared to 46%, <i>p</i> = 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.https://www.mdpi.com/2072-6694/13/19/4765alpha fetoproteinAFP-L3des-γ-carboxy prothrombinhepatocellular carcinomaliver-directed therapy |
| spellingShingle | Kelley G. Núñez Tyler Sandow Daniel Fort Jai Patel Mina Hibino Ian Carmody Ari J. Cohen Paul Thevenot Baseline Alpha-Fetoprotein, Alpha-Fetoprotein-L3, and Des-Gamma-Carboxy Prothrombin Biomarker Status in Bridge to Liver Transplant Outcomes for Hepatocellular Carcinoma Cancers alpha fetoprotein AFP-L3 des-γ-carboxy prothrombin hepatocellular carcinoma liver-directed therapy |
| title | Baseline Alpha-Fetoprotein, Alpha-Fetoprotein-L3, and Des-Gamma-Carboxy Prothrombin Biomarker Status in Bridge to Liver Transplant Outcomes for Hepatocellular Carcinoma |
| title_full | Baseline Alpha-Fetoprotein, Alpha-Fetoprotein-L3, and Des-Gamma-Carboxy Prothrombin Biomarker Status in Bridge to Liver Transplant Outcomes for Hepatocellular Carcinoma |
| title_fullStr | Baseline Alpha-Fetoprotein, Alpha-Fetoprotein-L3, and Des-Gamma-Carboxy Prothrombin Biomarker Status in Bridge to Liver Transplant Outcomes for Hepatocellular Carcinoma |
| title_full_unstemmed | Baseline Alpha-Fetoprotein, Alpha-Fetoprotein-L3, and Des-Gamma-Carboxy Prothrombin Biomarker Status in Bridge to Liver Transplant Outcomes for Hepatocellular Carcinoma |
| title_short | Baseline Alpha-Fetoprotein, Alpha-Fetoprotein-L3, and Des-Gamma-Carboxy Prothrombin Biomarker Status in Bridge to Liver Transplant Outcomes for Hepatocellular Carcinoma |
| title_sort | baseline alpha fetoprotein alpha fetoprotein l3 and des gamma carboxy prothrombin biomarker status in bridge to liver transplant outcomes for hepatocellular carcinoma |
| topic | alpha fetoprotein AFP-L3 des-γ-carboxy prothrombin hepatocellular carcinoma liver-directed therapy |
| url | https://www.mdpi.com/2072-6694/13/19/4765 |
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