Prognosis of first-line tumor directed therapy for hepatocellular carcinoma using a combination of AFP, AFP-L3, and DCP

Abstract

Presenter: Paul Thevenot PhD | Ochsner Health System Background: The expanded biomarker panel consisting of α-fetoprotein (AFP), AFP-L3%, and des-γ-carboxy prothrombin (DCP) has improved surveillance and early detection of hepatocellular carcinoma (HCC). The biomarkers individually, when elevated, have also been linked to aggressive tumor biology including vascular invasion and advanced staging. With increased clinical utilization on the horizon, we investigated the role of using biomarker combinations at the time of diagnosis and correlating the outcomes at the time of liver transplantation. Methods: This prospective study was conducted at a single-center in HCC patients presenting to a multi-disciplinary tumor board for liver-directed therapy (LDT) and evaluation for bridge to liver transplantation (8/30/16 – 10/16/20). AFP, AFP-L3%, and DCP were assayed on the day of first line LDT using the μTASWako i30 instrument. Additional analyzed parameters were also obtained prior to first-line LDT and monitored for bridge to transplant outcome as the primary study endpoint. Results: Consented for analysis were 140 treatment naïve HCC patients undergoing first line LDT with transarterial chemoembolization, Ytrrium-90, or microwave ablation. The median cohort age was 61 years with majority demographics of male (74%) and hepatitis C etiology (59%). Tumor burden was 82% within Milan with a median MELD-Na prioritization score of 11. Study endpoint breakdown was 29% transplanted, 29% dropout due to tumor progression, 24% censored from study endpoint, and 18% remaining waitlist active at the time of analysis. Median biomarker values were 10 ng/mL AFP, 7% AFP-L3, and 3.1 ng/mL DCP. Forty-four percent of cohort was negative for all three biomarkers while 14% were triple positive. Univariate analysis for each biomarker at threshold were associated with tumor progression (OR 5.6 – AFP > 20 ng/mL, 4.8 – AFP-L3 >10%, 8.8 – DCP >7.5 ng/mL). Analysis of cohort based on biomarker status (triple negative, AFP only, or positive for AFP-L3% and/or DCP) revealed an association between biomarker positivity and largest lesion size (P < 0.001). Univariate analysis showed largest lesion, and each individual biomarker, along with 2 positive biomarkers was associated with bridge to transplant survival. Controlling for tumor burden in separate multivariate analyses, AFP (HR 4.8), and DCP (HR 2.2), or having 2 positive biomarkers (HR 6.0) remained associated with bridge to transplant survival. In endpoint analysis, patients with more than 2 positive biomarkers had significant lower bridge to transplant survival. Biomarker positivity was also associated with response to first line LDT (OR 3.2). Conclusion: The expanded biomarker panel (AFP, AFP-L3%, and DCP) prior to LDT in bridge to transplant HCC can identify patients at high risk of tumor progression following LDT. The expanded biomarker panel may provide an opportunity to optimize treatment modality with outcome based on profile independent of radiographic tumor burden.