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:We aimed to determine the associations between the pretreatment Advanced Lung Cancer Inflammation Index (ALI) and survival outcomes in patients with unresectable hepatocellular carcinoma (u-HCC) who received atezolizumab plus bevacizumab (Atez/Bev). METHODS:This retrospective study analyzed 563 patients with u-HCC who were treated with Atez/Bev (Sept 2020-Dec 2024). The ALI was calculated according to Body Mass Index × serum albumin level/neutrophil-to-lymphocyte ratio. Associations between ALI and overall survival (OS) and progression-free survival (PFS) were evaluated by Cox proportional hazards regression analysis. RESULTS:An ALI cutoff value of 27.04, determined by receiver operating characteristic curve analysis, was used to classify patients into low- and high-ALI groups. High-ALI patients had longer median OS (26.1 vs. 13.7 months, p < 0.001) and PFS (9.3 vs. 5.2 months, p < 0.001), and a higher disease control rate (82.5% vs. 69.1%, p < 0.001) compared to low-ALI patients. Multivariate Cox regression analysis confirmed that a high ALI value was a significant prognostic marker for OS (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.54-0.88, p = 0.003) and PFS (HR: 0.75, 95% CI: 0.61-0.92, p = 0.006). Subgroup analyses showed that the trend toward improved outcomes was consistent for high ALI values in all clinically relevant subgroups. CONCLUSIONS:A high pretreatment ALI value was associated with improved survival and disease control in u-HCC patients receiving Atez/Bev, underscoring its potential utility as a prognostic marker for clinical management and further studies.
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.
QuestionDoes achieving guideline-recommended low-density lipoprotein cholesterol (LDL-C) levels help prevent neoatherosclerosis after drug-eluting stent implantation in patients with ST-segment elevation myocardial infarction (STEMI)?FindingsIn this secondary analysis of the CONNECT randomized clinical trial, neoatherosclerosis was less frequent in patients who achieved guideline-endorsed LDL-C levels and received high-intensity statin therapy. On-treatment LDL-C level emerged as an independent determinant of neoatherosclerosis.MeaningAchieving guideline-recommended LDL-C levels through intensive lipid-lowering therapy may help prevent neoatherosclerosis formation and prevent late stent failure in patients with STEMI. ImportanceNeoatherosclerosis represents a major cause of late stent failure and results in cardiac events after drug-eluting stent (DES) implantation. Achieving secondary preventive low-density lipoprotein cholesterol (LDL-C) target levels can reduce plaque progression in native coronary arteries; however, its association with neoatherosclerosis formation remains unclear.ObjectiveTo determine whether achieving guideline-endorsed LDL-C levels after DES implantation is associated with reduced risk of long-term neoatherosclerosis formation.Design, Setting, and ParticipantsThis is a post hoc analysis of the CONNECT randomized clinical trial conducted at 7 sites in Switzerland and Japan that had randomized 239 patients with ST-segment elevation myocardial infarction (STEMI) to percutaneous coronary intervention (PCI) with biodegradable- or durable-polymer everolimus-eluting stents between June 2017 and June 2020. The prevalence of neoatherosclerosis was assessed with optical coherence tomography (OCT) 3 years after primary PCI. Data analysis for this post hoc analysis was conducted from September 2024 to October 2025.InterventionPatients with STEMI received primary PCI with DES, and statin therapy was recommended according to country-specific guidelines.Main Outcomes and MeasuresThe prevalence of neoatherosclerosis 3 years after primary PCI was compared between patients with vs without achievement of guideline-endorsed target LDL-C levels. A multivariable predictor analysis was performed to determine whether on-treatment LDL-C levels were associated with occurrence of neoatherosclerosis.ResultsAmong 178 patients (mean [SD] age, 63.4 [10.9] years; 27 [15%] female) who underwent OCT at 3 years, 98 patients (55%) achieved the target LDL-C level and 80 patients (45%) did not. The mean (SD) on-treatment LDL-C levels for these groups were 48 (13) and 87 (37) mg/dL, respectively (to convert to millimoles per liter, multiply by 0.0259). The prevalence of neoatherosclerosis was lower in patients who achieved the target LDL-C level as compared with patients who did not (7 patients [7%] vs 15 patients [19%], respectively; odds ratio for those who did not achieve the LDL-C target level, 3.00; 95% CI, 1.19-8.24; P = .02). On-treatment LDL-C level (per 25-mg/dL increase) emerged as an independent determinant of neoatherosclerosis at 3 years in multivariable logistic regression analysis (odds ratio, 1.46; 95% CI, 1.09-2.01; P = .01).Conclusions and RelevanceOn-treatment LDL-C level emerged as an independent predictor of neoatherosclerosis 3 years after DES implantation for STEMI. Neoatherosclerosis was less frequent among patients who achieved the guideline-recommended on-treatment LDL-C level, underscoring the importance of LDL-C lowering in preventing neoatherosclerosis formation.Trial RegistrationClinicalTrials.gov Identifier: NCT03440801 This secondary analysis of the CONNECT randomized clinical trial evaluates whether achieving a guideline-endorsed low-density lipoprotein cholesterol level after drug-eluting stent implantation in patients with ST-segment elevation myocardial infarction (STEMI) is associated with reduced risk of long-term neoatherosclerosis formation.
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.
