Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma (CHANCE2201): a target trial emulation study.

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC. Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821. Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group. Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project.

Nomograms including the controlling nutritional status score in patients with hepatocellular carcinoma undergoing transarterial chemoembolisation for prediction survival: a retrospective analysis.

This retrospective study investigated the predictive value of the Controlling Nutritional Status (CONUT) score in patients with intermediate-stage hepatocellular carcinoma (HCC) who received transarterial chemoembolization (TACE). Nomograms were developed to predict progression-free and overall survival (PFS, OS). The medical data of 228 patients with HCC and treated with TACE were collected. The patients were apportioned to 2 groups according to CONUT score: low or high (<4, ≥4). Univariate and multivariate analyses were performed using Cox regression for OS and PFS. OS and PFS were estimated by the Kaplan-Meier curve and compared with the log-rank test. Nomograms were constructed to predict patient OS and PFS. The nomograms were evaluated for accuracy, discrimination, and efficiency. The cut-off value of CONUT score was 4. The higher the CONUT score, the worse the survival; Kaplan-Meier curves showed significant differences in OS and PFS between the low and high CONUT score groups (P = 0·033, 0·047). The nomograms including CONUT, based on the prognostic factors determined by the univariate and multivariate analyses, to predict survival in HCC after TACE were generated. The CONUT score is an important prognostic factor for both OS and PFS for patients with intermediate HCC who underwent TACE. The cut-off value of the CONUT score was 4. A high CONUT score suggests poor survival outcomes. Nomograms generated based on the CONUT score were good models to predict patient OS and PFS.

Nomogram Based on Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio to Predict Recurrence in Patients with Hepatocellular Carcinoma after Radiofrequency Ablation.

OBJECTIVES: To investigate the prognostic value of pre-procedure neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) and construct a nomogram to predict disease-free survival (DFS) in patients receiving radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) within Milan criteria. METHODS: The data of 515 patients of HCC within Milan criteria receiving RFA were retrospectively collected. The patients were divided into two groups: the training group (n = 382) and the validation group (n = 133). Several preprocedural variables were analyzed in the two groups to determine the prognostic factors. RESULTS: The median DFS time of the training and validation group was 28.4 months and 24.5 months, respectively. Multivariate analyses showed that number of lesions, alpha-feto protein levels, NLR and PLR were independent risk factors of DFS. According to the time-dependent receiver operating characteristic curve (t-ROC), the optimal cutoff value of the NLR and PLR was 1.55 and 75.30, respectively, with sensitivity of 0.737 and 0.648 and specificity of 0.541 and 0.508, respectively. The area under curve (AUC) of the t-ROC curves for the NLR was 0.662 and PLR was 0.597. The DFS was significantly higher in the NLR ≤ 1.55 group compared to NLR > 1.55 group and the PLR ≤ 75.30 group compared to PLR > 75.30 group in both training and validation datasets. Nomogram was developed based on the prognostic factors indicated by the Cox regression to predict 1-, 2-, 3- and 5-year DFS probabilities. CONCLUSIONS: The cutoff value of the NLR and PLR was 1.55 and 75.30. This new nomogram based on NLR and PLR may provide good and individualized prediction of recurrence for HCC patients within Milan criteria after RFA.

Clinical application of interventional embolization in tumor-associated hemorrhage.

Recently, the main clinical treatment methods for tumor-associated hemorrhage include systemic therapy, the application of hemostatic drugs, blood transfusion, symptomatic support therapy and endoscopic interventional hemostasis. Endoscopic hemostasis is performed mainly for patients with gastrointestinal bleeding, and the procedures include hardening of the blood vessels and the injection of hemostatic drugs. Surgical hemostasis methods mainly include the surgical ligation of bleeding blood vessels or tumor resection for hemostasis. Interventional hemostasis is a new hemostasis method. With the development of interventional radiology in recent years, transcatheter arterial embolization (TAE) can quickly detect and accurately embolize arterial blood vessels. It is the preferred treatment for present tumor-associated hemorrhages.

Using the Controlling Nutritional Status (CONUT) Score for Evaluating Patients with Early-Stage Hepatocellular Carcinoma After Radiofrequency Ablation: A Two-Center Retrospective Study.

PURPOSE: To estimate the prognostic significance of the controlling nutritional status (CONUT) in patients with BCLC stage A hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA). MATERIALS AND METHODS: From January 2013 to December 2016, 325 patients with BCLC stage A HCC who underwent RFA at the National Cancer Center and First Hospital of Shanxi Medical University were retrospectively studied. The patients were divided into low (≤ 4) and high (≥ 5) CONUT scores for assessment of overall survival (OS) and recurrence-free survival (RFS). Several covariates, including age, sex, the diameter and number of lesions, lesion differentiation, Child-Pugh class, hepatitis B virus infection, along with blood levels of AFP, AST, ALT, γ-GT, and TBIL, were assessed using univariate and multivariate analyses. RESULTS: The mortality rate was 17.49% (46/263) and 35.48% (22/62) in the low and high CONUT groups, respectively, with the difference being statistically significant (P = 0.033). In addition, disease recurrence was significantly higher in the high CONUT group at 70.97%, as compared to the low CONUT group at 43.35% (P = 0.041). The predictive factors were used to build the nomogram to estimate 1-, 3- and 5-year OS and RFS rates. CONCLUSIONS: CONUT scores were found to be associated with the prognosis of patients with early-stage HCC who underwent RFA. Higher CONUT scores were associated with poor survival outcomes.