Journal of Hepatocellular Carcinoma最新文献

Purpose: The purpose of This study is exploring the intraoperative and perioperative differences between patients undergoing conversion surgery and those undergoing direct surgery, so as to improve preoperative preparation.

Methods: The retrospective study was approved by an ethics review committee. A total of 232 patients with hepatocellular carcinoma who underwent surgical resection at the First Affiliated Hospital of Chongqing Medical University from September 2022 to December 2023 were included, comprising 210 operating patients and 53 conversion patients. Propensity score matching was employed for comparison in order to minimize bias.

Results: The conversion group had more intraoperative bleeding (each P=0.001), longer operation time (P=0.033; PSM p=0.025), and higher intraoperative blood transfusion rate (p=0.001; PSM p=0.044). The incidence of perioperative complications, including perioperative ascites formation (p=0.011; PSM p=0.005), moderate to severe anemia (p=0.001; PSM p=0.002), postoperative blood transfusion (p=0.004; PSM p=0.036), and postoperative ICU transfer (p=0.041; PSM p=0.025), was higher in the conversion group compared to the operation group. The postoperative hospital stay (p=0.001; PSM p=0.003) was prolonged in the conversion group.

Conclusion: Post-conversion operations carry a higher risk of bleeding and are more likely to result in moderate to severe anemia and ascites formation in the perioperative period. However, the risk is reversible with adequate preoperative blood preparation and prompt postoperative symptomatic treatment. Conversion patients should be encouraged to undergo operating therapy when they can withstand surgical resection.

Background: For patients with large unresectable hepatocellular carcinoma (HCC), the effectiveness of conventional transarterial chemoembolization (TACE) remains suboptimal, which necessitates the administration of substantial volumes of chemotherapy drugs and lipiodol, thereby increasing the risk of liver failure and other chemotherapy-related complications. Therefore, we devised a strategy of initial hepatic arterial infusion chemotherapy (HAIC) followed by sequential drug-eluting bead TACE (DEB-TACE). In our treatment design, a lower tumor burden after HAIC facilitated complete embolization of tumor vasculature, and the use of less amount of embolic agents reduced the incidence of liver failure and embolization syndromes.

Methods: This retrospective study evaluated consecutive patients with unresectable large HCC with a maximum tumor diameter of ≥7 cm who received FOLFOX-HAIC combined with sequential DEB-TACE from April 2019 to February 2024. Efficacy was evaluated using the objective response rate (ORR), overall survival (OS), and progression-free survival (PFS); and safety was assessed using the frequency of key adverse events (AEs).

Results: Among the 76 patients included, the median maximum tumor diameter was 12.4 cm (range, 7.0-23.4 cm). The overall ORRs based on mRECIST and RECIST 1.1 criteria were 94.1% and 51.5%, respectively. The median OS was 28.1 months (95% CI, 22.7-33.4), and the median PFS was 11.7 months (95% CI, 7.7-15.8). All patients experienced AEs, but only 18.4% experienced grade 3 or 4 AEs, there was no treatment-related mortality.

Conclusion: In this single-center, retrospective study, our results suggested that FOLFOX-HAIC with sequential DEB-TACE demonstrated promising efficacy and safety for patients with unresectable HCC with a maximum tumor diameter of ≥7 cm.

Background: The close association between inflammation and the clinical outcomes of hepatocellular carcinoma (HCC) has been extensively documented. This study aims to analyze the association between a novel inflammatory indicator, the gamma-glutamyl transpeptidase to neutrophil ratio (GNR), and HCC prognosis following curative resection.

Methods: A cohort of 204 eligible HCC cases were included. Based on an optimal cut-off value determined utilizing the X-tile software, patients were categorized into low- and high-GNR groups. The overall survival (OS) and recurrence-free survival (RFS) rates were assessed using the Kaplan-Meier analysis method with Log rank tests. Multivariate Cox proportional hazard regression was used to investigate the independent association between GNR and HCC prognosis. Restricted cubic splines were used to explore the nonlinear relationship between GNR and the risk of death or recurrence.

Results: The low GNR group exhibited significantly higher 3-year OS and RFS rates than the high GNR group. Multivariate Cox analysis indicated that a high GNR level was independently associated with poor OS and RFS. A linear correlation between GNR and the risk of death, as well as a nonlinear inverted "U" shape correlation between GNR and the risk of recurrence, were observed.

Conclusion: The findings provide evidence supporting the independent association of GNR with HCC prognosis. These results offer promise for enhancing prognosis assessments and guiding active monitoring strategies for patients with HCC post-curative resection.

Purpose: To evaluate safety, preliminary efficacy, pharmacokinetics, and pharmacodynamics, of fostroxacitabine bralpamide (fostrox, MIV-818), a novel oral troxacitabine nucleotide prodrug designed to direct exposure to the liver, while minimizing systemic toxicity.

Patients and methods: Fostrox monotherapy was administered in an open-label, single-arm, first-in-human, phase 1a/1b study, in patients with hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma, or solid tumor liver metastases. The first part (1a) consisted of intra/inter-patient escalating doses (3 mg to 70 mg) QD for up to 5 days, and the second part (1b), doses of 40 mg QD for 5 days, in 21-day cycles. Safety and tolerability were evaluated by the Safety Review Committee, and efficacy was assessed every 6 weeks with CT or MRI using RECIST 1.1 and mRECIST.

Results: Nineteen patients were treated with fostrox. Most common adverse events (AEs) were hematological and increased AST. Grade 3 treatment related AEs (TRAE) were seen in 53% of the patients, with transient neutropenia and thrombocytopenia as the most common. No grade 5 AE was observed. Recommended Phase 2 dose of fostrox was 40 mg QD for 5 days in 21-day cycles. Preliminary efficacy showed a clinical benefit rate in the liver of 53% and stable disease (SD) as best response in 10 patients. Liver targeting with fostrox was confirmed with higher exposure of troxacitabine and its metabolites in liver compared to plasma. Systemic exposure of fostrox was generally low with troxacitabine as main analyte. Biopsies demonstrated tumor-selective, drug-induced DNA damage.

Conclusion: The phase 1a/1b monotherapy study of fostrox, in patients with liver tumors, showed a tumor selective effect in the liver and that 40 mg QD for 5 days in 21-day cycles is safe and tolerable. Safety and preliminary efficacy in patients with advanced HCC supports clinical development of fostrox in combination with other modes of action in HCC.

Objective: To develop a model for predicting the overall survival (OS) of hepatocellular carcinoma (HCC) patients after transarterial chemoembolization (TACE) on the basis of multisequence MRI radiomic features and clinical variables.

Methods: The DCE-MRI and clinical data of 116 HCC patients treated with TACE for the first time were retrospectively analyzed. The included patients were randomly divided into training and validation cohorts at a ratio of 7:3. Univariate and multivariate Cox proportional hazards regression models were used to identify independent risk factors that affect the OS of patients with HCC after TACE. Radiomic features were extracted from the sequences of FS-T2W images and arterial-phase (A) and portal venous-phase (P) axial DCE-MR images. The LASSO method was used to select the best radiomic features. Logistic regression was used to establish a radiomic model of each sequence, a joint model of MRI features (M model) combined the radiomic features of all the sequences, and a radiomic-clinical model (M-C model) that integrated the radiomic signatures and clinically independent predictors. The diagnostic performance of each model was evaluated as the area under the receiver operating characteristic (ROC) curve (AUC).

Results: The Child-Turcotte-Pugh (CTP) score and neutrophil-to-lymphocyte ratio (NLR) -platelet-to-lymphocyte ratio (PLR) were found to be independent risk factors that affect the OS of patients with HCC treated with TACE. The AUCs of the FS-T₂WI, A, P, M, and M-C models for predicting the OS of HCC patients after TACE treatment were 0.779, 0.803, 0.745, 0.858 and 0.893, respectively, in the training group and 0.635, 0.651, 0.644, 0.778 and 0.803, respectively, in the validation group. The M-C model had the best predictive performance.

Conclusion: Multiparameter MRI-based radiomic features may be helpful for predicting OS after TACE treatment in HCC patients. The inclusion of clinical indicators such as inflammation scores can improve the predictive performance.

Purpose: This research aims to compare the efficacy of neoadjuvant hepatic arterial infusion chemotherapy (HAIC) combined with Lenvatinib (Len) to direct liver resection (LR) in patients with resectable or borderline resectable hepatocellular carcinoma (HCC).

Methods: This retrospective study included 154 patients with hepatocellular carcinoma (HCC) treated at the a large-scale hepatocellular carcinoma Research Center between March 2019 and June 2023. Patients were assigned to one of two groups: 63 received neoadjuvant hepatic arterial infusion chemotherapy (HAIC) combined with Lenvatinib followed by liver resection (HAIC+Len→LR), while 91 received direct liver resection (LR). The primary outcomes assessed were median overall survival (mOS), median progression-free survival (mPFS), median duration of response (mDOR), and adverse events (AEs).

Results: Patients in the HAIC+Len→LR group demonstrated significantly longer median overall survival (mOS) (40.1 months vs 35.9 months, P=0.001) and median progression-free survival (mPFS) (32.8 months vs 23.8 months, P=0.0023) compared to the LR group. Preoperative complete response (CR) to HAIC was associated with better median duration of response (mDOR) and mOS compared to partial response (PR) (not reached vs 28.9 months, P=0.006; 40.0 vs 29.1 months, P=0.037). Subgroup analysis revealed no significant difference in OS or PFS between the HAIC+Len→LR and LR groups in early Barcelona Clinic Liver Cancer (BCLC) stages. However, in late BCLC stages, the HAIC+Len→LR group exhibited significantly improved OS and PFS (HR 0.471, P=0.016; HR 0.551, P=0.022). Treatment-related grade ≥3 adverse events were comparable between the two groups.

Conclusion: For patients with resectable or marginally resectable HCC in the intermediate to advanced stages of BCLC, surgery after neoadjuvant HAIC+Len may offer improved long-term prognosis.

Objective: To explore changing trends in circulating immune indicators of hepatocellular carcinoma (HCC) undergoing TACE plus immune checkpoint inhibitors (ICIs) and anti-VEGF antibodies/TKIs and to elucidate the relationship between immune response and tumor prognosis.

Materials: This single-center retrospective study included patients with unresectable HCC undergoing TACE plus ICIs and anti-VEGF antibodies/TKIs from March 11, 2019, to February 15, 2024. Peripheral blood samples were collected at baseline and every cycle, from which blood cell counts and immune indicators were analyzed. The primary outcome was the objective response rate (ORR) at the first evaluation. According to the first evaluation based on mRECIST, patients were classified into PD, SD, and OR groups for analysis. Further subgroup analysis was performed on the OR group based on whether experiencing progression after the first evaluation. Lymphocyte subsets were measured by flow cytometry. Immunoglobulins were measured using the immune turbidimetric method. The neutrophil-to-lymphocyte ratio (NLR) was measured by the complete blood count. Simple linear regression was employed to examine the dynamic trends.

Results: A total of 63 patients were enrolled, with an ORR of 55.6% and a disease control rate (DCR) of 87.3% at the first evaluation. The median overall survival (mOS) was 27.5 months (95% CI: 22.5-32.5 months). In the OR group (n=35), more active immune responses, expressed in a decrease in CD3^-CD19⁺ (p=0.004), CFB (p=0.027), NLR (p<0.001) and an increase in Ig λ (p=0.010), Ig κ (p=0.037), Ig A (p=0.005), Ig G (p=0.006), were related to better prognosis, while similar patterns seen in the OR-nPD subgroup. Concurrently, no significant differences were noted in the PD group (n=8).

Conclusion: The combination therapy may modify the tumor microenvironment of HCC. Changing trends in circulating immune indicators and NLR can serve as potential biomarkers for predicting tumor response and guiding clinical treatment.

Purpose: There are insufficient data about the optimal treatment for older patients with recurring medium or large hepatocellular carcinoma (HCC). The study intended to assess the effect of transcatheter arterial chemoembolization combined with microwave ablation (TACE-MWA) in an elderly cohort through a retrospective analysis.

Methods: From 2011 to 2018, a cohort of individuals (age ≥70 years) with recurrent HCC tumors ranging from 3.1 cm to 7 cm underwent either a combination treatment of TACE and MWA (n = 43) or surgical intervention (n = 33). Using the Inverse Probability of Treatment Weighting (IPTW) technique, factors of disease-free survival (DFS), overall survival (OS), and rates of major adverse events were analyzed, retrospectively.

Results: The group that underwent surgery had a greater history of alcohol use before treatment (P= 0.001), as well as a higher Barcelona Clinic Liver Cancer (BCLC) stage for the primary tumor before treatment (P= 0.014) and a higher primary tumor location before treatment (P= 0.045). The TACE-MWA group had DFS rates of 86.2%, 68.8%, and 60.4% at 1, 3, and 5 years, while the surgery group had rates of 53.0%, 42.2%, and 25.8% at the same time points. In the TACE-MWA treatment group, survival rates at 1 year, 3 years, and 5 years post-treatment were recorded as 93.0%, 80.8%, and 65.7%, respectively, while in the surgery group, they were 62.7%, 46.9%, and 42.6%. In the univariate analysis using IPTW, the type of treatment was found to have a significant correlation with disease progression (hazard ratio [HR] 0.41, 95% CI 0.20-0.86, P=0.017). IPTW multivariate analysis showed that treatment modality (HR, 0.35; 95% CI, 0.17 to 0.79; P= 0.011) was the only significant prognostic factor for OS.

Conclusion: In elderly patients with recurrent 3.1 cm≤ HCC ≤ 7 cm, TACE-WMA was superior to surgery in the respects of DFS and OS.

Purpose: Hepatocellular carcinoma (HCC) represents a significant global health problem, requiring precise prognostic tools for optimal treatment stratification. This study aimed to develop a new risk prediction score, called AD score, based on the serum markers alpha-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP), to offer an objective and accurate preoperative assessment of HCC in patients undergoing transarterial chemoembolization (TACE).

Patients and methods: This was a retrospective study that included 295 HCC patients who were subjected to TACE (training set, n=147; testing set, n=148). Serum AFP and DCP levels were log-transformed to construct the AD score. Multivariate Cox regression analysis on cirrhosis subgroups validated the objectivity of the model. Performance comparison of established models (Child Pugh, BCLC, ALBI, Up-to-seven, Six-and-twelve, Four and seven, HAP score, mHAP-II, FAIL-T score), was assessed through time-dependent receiver operating characteristic (ROC) curves and risk stratification.

Results: The AD score, incorporating lgAFP and lgDCP, demonstrated superior predictive accuracy than the existing models. Time-dependent ROC curve revealed the consistent superiority of the AD score over a 5-year period. The risk stratification into low, intermediate, and high group based on the AD score showed a significant survival difference in both training and testing set.

Conclusion: For HCC patients undergoing TACE, the AD score serves as an objective and straightforward prognostic tool, enhancing predictive accuracy and showcasing its clinical utility. It demonstrates potential significance as a crucial addition to preoperative risk assessment for TACE.

Purpose: Transarterial chemoembolization (TACE), when used in combination with immunotherapy and antiangiogenic therapy, has been shown to have synergistic anticancer effects. The aim of this study was to further assess the efficacy and safety of TACE combined with atezolizumab and bevacizumab in the treatment of unresectable hepatocellular carcinoma (HCC) in the real world.

Methods: Between August 2021 and September 2023, clinical information was collected from consecutive HCC patients who received treatment via TACE-Atezo/Bev at four tertiary institutions. This study evaluated the objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) as outcomes. Predictors for OS and PFS were also analyzed. Treatment-related adverse events (TRAEs) were recorded and assessed.

Results: Ninety-two patients were enrolled in this study, with a median follow-up duration of 14.1 months. The ORRs based on the modified Response Evaluation Criteria in Solid Tumors (RECIST) and RECIST 1.1 criteria were 54.3% and 41.3%, respectively. The median OS and PFS of the patients were 15.9 months [95% confidence interval (CI), 14.5-17.2 months] and 9.1 months (95% CI, 7.4-10.8 months), respectively. Multivariate analyses revealed that the Eastern Cooperative Oncology Group score and neutrophil‒lymphocyte ratio were independent risk factors for OS, whereas tumor size and extrahepatic metastasis were independent risk factors for PFS. Grade 3/4 TRAEs occurred in 16.3% (15/92) of the patients and were controlled conservatively.

Conclusion: The combination of Atezo/Bev with TACE demonstrated acceptable synergistic therapeutic effects and manageable safety profiles in patients with unresectable HCC.