In patients with hepatocellular carcinoma who were bridged to transplantation, favorable tumor biology and immune status were correlated with objective response prior to liver transplantation and, most importantly, objective response to transcatheter arterial chemoembolization with doxorubicin-eluting microspheres may enable selection of patients who are ideal candidates for liver transplantation. PurposeTo assess response to transcatheter arterial chemoembolization (TACE) based on immune markers and tumor biology in patients with hepatocellular carcinoma (HCC) who were bridged to liver transplantation, and to produce an optimized pretransplantation model for posttransplantation recurrence risk.Materials and MethodsIn this institutional review board–approved HIPAA-compliant retrospective analysis, 93 consecutive patients (73 male, 20 female; mean age, 59.6 years; age range, 23–72 years) underwent TACE with doxorubicin-eluting microspheres (DEB) (hereafter, DEB-TACE) and subsequently underwent transplantation over a 5-year period from July 7, 2011, to May 16, 2016. DEB-TACE response was based on modified Response Evaluation Criteria in Solid Tumors. Imaging responses and posttransplantation recurrence were compared with demographics, liver function, basic immune markers, treatment dose, and tumor morphology. Treatment response and recurrence were analyzed with uni- and multivariate statistics, as we...

Due to active hepatocellular carcinoma (HCC) surveillance, many patients are diagnosed with early-stage disease and are usually amendable to curative treatments. These patients lack poor prognostic factors associated with Milan Criteria and alpha fetoprotein (AFP) biomarker levels. There are currently limited strategies to assess prognosis in the patients who remain at risk of post-treatment HCC progression. In a cohort of liver transplant (LT) candidates with HCC, this study seeks to identify factors prior to liver-directed therapy (LDT) associated with time to progression (TTP). This is a retrospective analysis of prospectively collected data from LT candidates with recently diagnosed HCC and receiving LDT as a bridge to LT at three interventional oncology programs within a single system (n = 373). Demographics, clinical hepatology and serology, and factors related to HCC burden were extracted and analyzed for associations with TTP risk. Albumin level below the cohort median (3.4 g/dL) emerged as an independent risk factor for TTP controlling for AFP > 20 ng/mL as well as Milan, T-stage, and Barcelona Clinic Liver Cancer (BCLC) stage individually. In modality-specific subgroup survival analysis, albumin-based TTP stratification was restricted to patients receiving first cycle microwave ablation (p = 0.007). In n = 162 patients matching all low-risk criteria for Milan, T-stage, BCLC stage, and AFP, the effect of albumin < 3.4 g/dL remained significant for TTP (p = 0.004) with 2-year TTP rates of 68% (<3.4 g/dL) compared to 95% (≥3.4 g/dL). In optimal bridge to LT candidates with small HCC and low AFP biomarker levels, albumin level at treatment baseline provides an HCC-independent positive prognostic factor for risk of HCC progression prior to LT.

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.

Immune checkpoint inhibitors (ICIs) have emerged as first-line therapy for advanced-stage HCC with modest response rates (<33%). Combination treatments offer the potential to improve response rates while improving outcomes. This study evaluates the safety and outcomes of first-line Yttrium-90 plus ICI (⁹⁰Y-ICI). A retrospective, multi-center study was conducted in HCC patients receiving first-line ⁹⁰Y-ICI with atezolizumab plus bevacizumab (Atezo/Bev) or tremelimumab plus durvalumab (Treme/Durva). Treatment response was evaluated at follow-up for planned ⁹⁰Y treatment cycle. Time-to-event measures of time to progression (TTP), progression-free survival (PFS), and overall survival (OS) served as primary endpoints, with first cycle response rates and AEs as secondary outcomes. This study included 37 patients receiving ⁹⁰Y-ICI from 2021 to 2024 (16-month median follow-up). The cohort was predominantly Child-Pugh A (92%) with HCV-related cirrhosis (67%), advanced stage (54%), and a median index HCC size of 8.0 cm (IQR: 6—12 cm). Grade 3–4 AEs occurred in six patients (16%). The target objective response (OR) rate was 83%, with a 50% target complete response (CR) rate. Overall OR was 61% with an overall CR of 39%. Median PFS was 11 months with 1-year rates of 50%. Patients with a target CR had improved TTP (p = 0.004), PFS (p = 0.003), and OS (p = 0.003). The cohort’s 2-year OS was 41% with a median OS of 19 months (CI: 12–37 months). First-line ⁹⁰Y-ICI therapy in HCC is safe and effective, with no deviation in anticipated results. Patients achieving target CR showed significantly improved TTP, PFS, and OS, supporting target CR as an optimal treatment target.