Juan Gimenez

Background/Objectives: Identifying aggressive tumor biology within early-stage hepatocellular carcinoma (HCC) remains challenging. Scores based on liver function, systemic inflammation, and HCC biomarkers have been linked to overall survival prognosis; however, the combined ability of these scores to assess tumor-specific prognosis in early-stage disease is unclear. In this single-center, prospective study, biomarker profiling with AFP, AFP-L3, and DCP, along with modified albumin–bilirubin (mALBI), and neutrophil–lymphocyte ratio (NLR)/platelet–lymphocyte ratios (PLRs) were evaluated to determine their prognostic role in assessing clinical manifestations of aggressive biology by stratifying HCC progression risk. Methods: Indices and biomarkers were assessed at BCLC-A-stage HCC diagnosis and prior to liver-directed therapy (LDT). The primary prospective study endpoint was time-to-advanced-stage tumor progression (TTP). Results: The cohort included 232 patients diagnosed with early-stage HCC who underwent treatment with LDT. A multivariate model revealed that mALBI grade (p = 0.021), cumulative lesion size (p = 0.005), and elevations in HCC biomarkers (p < 0.001) were associated with TTP. Biomarker profile stratified TTP (p < 0.001) in which patients with complex profiles (3+) had 1-year progression risks of 69%. The biomarker system retained the ability to stratify TTP within small (≤3 cm) and large (>3 cm) cumulative tumor burden (p < 0.001, p = 0.005). While PLR was not prognostic for TTP, NLR disappeared from the multivariate model and mALBI stratified long-term progression risk (p = 0.003). In low-complex biomarker patients (0–1+), mALBI stratified progression risk (p = 0.001). Conclusions: Multi-positive biomarker profiling in early-stage HCC identifies a population with clinical manifestations of aggressive tumor biology at high risk of rapid post-treatment disease progression that may benefit from more aggressive treatment approaches. In patients with low-risk biomarker profiles (0–1+), mALBI can assess longer-term (>1-year) post-treatment disease progression risk, while scores based on systemic inflammation were not associated with tumor-restricted outcomes.

Among patients with treatment-naive hepatocellular carcinoma, glass microsphere radiation segmentectomy before liver transplant achieved high rates of complete pathologic necrosis, which was positively associated with the number of optimized treatment parameter thresholds.

Background: Drug-eluting bead transarterial chemoembolization (DEB-TACE) and yttrium-90 ( ⁹⁰ Y) radioembolization are approved therapies to treat hepatocellular carcinoma (HCC). Several randomized controlled trials and propensity score-matched studies (PSM) have been conducted to compare these 2 treatments; many utilized ⁹⁰ Y standard dosimetry (90 Y personalized dosimetry, which yields tumor doses exceeding 205 Gy. Purpose: This study utilized PSM between DEB-TACE and ⁹⁰ Y with personalized dosimetry to compare treatment and patient outcomes in Barcelona Clinic Liver Cancer (BCLC) A–B HCC. Methods: This retrospective study included 258 patients with unresectable BCLC A–B stage HCC treated with DEB-TACE or ⁹⁰ Y as the initial treatment approach from 2015 to 2024. PSM was performed ( ⁹⁰ Y:DEB-TACE), matching for tumor burden and alpha-fetoprotein levels at diagnosis. The primary endpoint was target response rate with secondary endpoints of overall response, target retreatment rate (TTR), target and overall time-to-progression (TTP), and overall survival (OS). Results: Overall, ⁹⁰ Y achieved significantly higher target complete (CR) and objective response (OR) rates compared with DEB-TACE (71% vs. 33% and 88% vs. 58%), respectively. In multifocal disease, target CR rates were higher following ⁹⁰ Y (68% vs. 13%). ⁹⁰ Y also yielded a longer duration of CR with a 1-year target retreatment rate of 12% compared with 40% with DEB-TACE. This translated into a longer target TPP ( p =0.030) with ⁹⁰ Y, although overall TPP and OS were similar between treatment modalities. In multifocal disease, ⁹⁰ Y generated superior response rates as well as target ( p =0.007) and overall TTP ( p =0.015). Conclusions: ⁹⁰ Y with personalized dosimetry achieved higher response rates and extended the duration of complete responses compared with DEB-TACE. ⁹⁰ Y was also more effective at treating multifocal disease.

Transarterial radioembolization (TARE) is an established therapy for primary and secondary hepatic malignancies. Outcomes depend heavily on dosimetry, which has evolved from empirical and body-surface-area methods to partition and voxel-based approaches. This review summarizes current evidence for advanced (personalized) dosimetry across tumor types, highlights emerging dose–response concepts, and outlines practical barriers and implementation strategies. A narrative review of peer-reviewed clinical studies and trials evaluating dosimetry in TARE, with emphasis on hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), metastatic colorectal cancer (mCRC), neuroendocrine tumor (NET), and breast cancer liver metastases, was performed with comparison of single-compartment medical internal radiation dosimetry method (MIRD), partition (multicompartment) methods, and voxel-based dosimetry methodologies. Personalized dosimetry improves outcomes in multiple tumor types. A randomized trial in HCC showed superior overall survival with partition-based dosing versus MIRD. In selective HCC treatments, voxel-derived metrics (e.g., D95) correlate with complete pathologic necrosis, suggesting benefit beyond mean dose targets. For iCCA, data associate higher tumor doses with better radiologic response, progression-free survival, and downstaging. In mCRC, voxel-based and threshold analyses link specific tumor and margin doses with metabolic/radiographic response and survival. Smaller series in NET and breast cancer indicate dose–response relationships using advanced dosimetry. Evidence supports broader adoption of advanced dosimetry in TARE. Emerging strategies that ensure adequate coverage of the “coldest” tumor regions and thoughtful particle-load planning may further optimize results. Standardized protocols, prospective validation, and scalable workflows are needed to accelerate implementation.

Immune checkpoint inhibitors (ICIs) have emerged as first-line therapy for advanced-stage HCC with modest response rates (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.