BACKGROUND AND AIMS:This multicenter retrospective study in Japan aimed to investigate the prognostic significance of lymphocyte-to-monocyte ratio (LMR) in patients with unresectable hepatocellular carcinoma (HCC) treated with durvalumab plus tremelimumab (Dur/Tre). METHODS:A total of 377 patients with HCC and treated with Dur/Tre across 30 institutions in Japan were included in this multicenter study. Time-dependent receiver operating characteristic (ROC) analysis was performed to determine the optimal LMR cut-off value. Hazard ratio (HR) spline curve analysis was used to identify the optimal LMR range for predicting progression-free survival (PFS) and overall survival (OS). RESULTS:Time-dependent ROC analysis identified an optimal LMR cut-off value of 2.52 for predicting median OS. Multivariate analysis demonstrated that an LMR of ≥ 2.52 was independently associated with superior PFS (HR: 0.777) and OS (HR: 0.657). The median PFS was 2.6 months in patients with an LMR of < 2.52, compared with 3.5 months in those with an LMR of ≥ 2.52 (p = 0.022). The median OS was 12.8 months in patients with an LMR of < 2.52, compared with 23.4 months in those with an LMR of ≥ 2.52 (p < 0.001). The disease control rate was significantly higher in the high LMR group (p = 0.032). The HR spline curve analysis revealed that an LMR range of approximately 1.8-2.6 represents an optimal cut-off for predicting both PFS and OS. CONCLUSIONS:LMR is a readily accessible prognostic biomarker for both PFS and OS in patients with unresectable HCC treated with Dur/Tre, and may serve as a practical tool for risk stratification in clinical practice.
AIM:Evidence regarding the optimal first-line immune checkpoint inhibitor (ICI) regimen for treating unresectable hepatocellular carcinoma (uHCC) with Child-Pugh class B (CP-B) liver function remains limited. This study compared atezolizumab plus bevacizumab (Atez/Bev) and durvalumab plus tremelimumab (Dur/Tre group) in real-world settings. METHODS:In this multicenter retrospective study, 211 consecutive patients with uHCC and CP-B liver function who underwent ICI-based therapy as a first-line therapy were analyzed. Treatment responses, survival outcomes, albumin-bilirubin (ALBI) score changes, and adverse events were evaluated. Survival analyses were adjusted using inverse probability weighting (IPW). RESULTS:The median progression-free survival associated with the Atez/Bev and Dur/Tre regimens was 5.0 and 3.5 months, respectively; the median corresponding overall survival was 10.5 and 12.4 months. After IPW adjustment, no significant differences were observed in progression-free or overall survival. The Atez/Bev regimen-associated disease control rate was significantly higher (75.2% vs. 55.0%, p = 0.02). The Dur/Tre regimen, meanwhile, was associated with a significantly higher immune-related adverse event incidence (10.5% vs. 32.7%, p < 0.01) and a greater need for high-dose corticosteroid treatment. In contrast, the Atez/Bev regimen resulted in a progressive decrease in ALBI scores, whereas the Dur/Tre regimen maintained the hepatic functional reserve. CONCLUSIONS:The Atez/Bev and Dur/Tre regimens afforded comparable survival outcomes but differed substantially in safety and effects on the hepatic functional reserve. Given the trade-off between immunotoxicity and liver function preservation, treatment selection for CP-B liver function should be individualized, considering baseline hepatic reserve, tolerability, and anticipated treatment trajectory.
Background & Aims Several clinical risk models have been proposed to stratify hepatocellular carcinoma (HCC) risk in patients with chronic hepatitis C virus (HCV) after sustained virologic response (SVR). However, validation efforts have focused on monocentric or country-specific cohorts, and it is unclear if clinical risk models can be broadly applied to global populations. We characterised regional variation in model performance for HCC risk stratification in post-SVR patients.Methods Four HCC clinical risk models (aMAP score, FIB-4 index, GES score, and Toronto HCC risk index [THRI]) were analysed in six real-world cohorts, which included 8796 post-SVR patients from different geographic regions globally. Model discrimination was assessed using Harrel's c-statistic index. HCC incidence rates were compared across low-, intermediate-, and high-risk groups for each model.Results Distributions of patient characteristics and HCC incidence rates varied across geographic regions. Predictive performances of models were comparable within each cohort despite the model with the highest c-statistics differing by regions. Performance was lower than those from original reports overall; c-statistics of models across most regions remained below 0.70.Conclusions There remains a continued need to improve discrimination and calibration of clinical models to stratify HCC risk in post-SVR patients. Accuracy of models may differ by geographic region, underscoring the importance of external validation to assess transportability of models and suggesting no single model can be universally applied.
