Conventional Transarterial Chemoembolization Versus Drug-Eluting Beads in Patients with Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Hepatocellular carcinoma (HCC) occurs in nearly three-quarters of all primary liver cancers, with the majority not amenable to curative therapies. We therefore aimed to re-evaluate the safety, efficacy, and survival benefits of treating patients with drug-eluting beads transcatheter arterial chemoembolization (DEB-TACE) compared to the conventional transcatheter arterial chemoembolization (C-TACE). Several databases were searched with a strict eligibility criterion for studies reporting on adult patients with unresectable or recurrent HCC. The pooled analysis included 34 studies involving 4841 HCC patients with a median follow-up of 1.5 to 18 months. There were no significant differences between DEB-TACE and C-TACE with regard to complete response, partial response and disease stability. However, disease control (OR: 1.42 (95% CI (1.03,1.96) and objective response (OR: 1.33 (95% CI (0.99, 1.79) were significantly more effective for DEB-TACE treatment with fewer severe complications and all-cause mortality. The pooled-analysis did not find superiority of DEB-TACE in complete or partial response, disease stability, controlling disease progression, and 30 day or end-mortality. However, results showed that DEB-TACE is associated with a better objective response, disease control, and lower all-cause mortality with severe complications compared to C-TACE treatment. Given that the safety outcomes are based on limited studies with a potential for bias, there was no clear improvement of DEB-TACE over C-TACE treatment.

Efficacy and Safety of Central Memory T Cells Combined With Adjuvant Therapy to Prevent Recurrence of Hepatocellular Carcinoma With Microvascular Invasion: A Pilot Study

BackgroundPostoperative adjuvant transcatheter arterial chemoembolization (TACE) following curative hepatectomy has been reported to improve the clinical outcomes of hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI), but more endeavors are required to achieve greater clinical benefit. Central memory T-cell (Tcm) self-transfusion has shown superior antitumor activity in several preclinical studies; however, clinical studies are rare. The aim of this study was to evaluate the clinical benefit and safety of combination treatment with Tcm self-transfusion and TACE as adjuvant treatment in HCC patients with MVI after curative hepatectomy.MethodsFrom October 2016 to September 2018, primary HCC patients with histologically confirmed MVI who underwent curative hepatectomy at the Cancer Hospital of the Chinese Academy of Medical Sciences were recruited for this study. The patients were divided into a Tcm group (combined Tcm self-transfusion with TACE treatment) or a control group (TACE treatment alone) according to their willingness. The recurrence-free survival (RFS), quality-of-life (QOL) score, and adverse events of each patient were recorded within 2 years.ResultsA total of 52 patients were enrolled, and 48 were eligible for the final data analysis. The median follow-up time was 20.5 months (95% CI: 17.05–22.55 months). The median RFS time was 9.5 months in the control group; the cutoff date was not reached in the Tcm group (when the follow-up duration was 12 months, p = 0.049, HR = 0.40; 95% CI: 0.16–0.99). Compared with the control group, 1- and 2-year RFS rates were higher in the Tcm group (72.0% vs. 46.4% and 58.18% vs. 39.14%, respectively). Multivariate analysis did not indicate that Tcm treatment was an independent prognostic factor associated with HCC recurrence (p = 0.107, HR = 2.312; 95% CI: 0.835–6.400), which might be due to the small sample size of this study. Nevertheless, Tcm treatment effectively improved a reduced QOL due to HCC and liver function injury. Finally, the safety profile of Tcm treatment in this study was good, without any serious adverse events.ConclusionsThis pilot study showed that Tcm self-transfusion combined with TACE treatment might be a beneficial adjuvant therapy with good safety for primary HCC patients with MVI after curative hepatectomy.Trial registration numberNCT03575806

Liver abscess after drug-eluting bead chemoembolization in patients with metastatic hepatic tumors

Objective: To investigate the incidence and risk factors for liver abscess formation after treatment with drug-eluting bead chemoembolization (DEB-TACE) in patients with metastatic hepatic tumors (MHT). Methods: The current study is a retrospective analysis of the clinical data of 137 patients with metastatic hepatic tumors who received DEB-TACE treatment in our institute between June 2015 and September 2020. Patients were evaluated for the presence or absence of post-DEB-TACE liver abscess. Univariate and multivariate analyses were used to identify risk factors for liver abscess formation. Results: The incidence of liver abscess formation after the DEB-TACE procedure was 8.76% per patient and 5.53% per procedure. Univariate analysis showed that larger maximum tumor diameter (p = 0.004), Grade one artery occlusion (p < 0.001) and systemic chemotherapy within 3 months before the DEB-TACE procedure (p < 0.001) were all associated with liver abscess formation. However, only systemic chemotherapy within 3 months before the DEB-TACE procedure (OR 5.49; 95% CI 0.34–13.54; p < 0.001) was identified by multivariate analysis to be an independent risk factor. Conclusions: Tumor size, Grade one artery occlusion and recent systemic chemotherapy may all be associated with increased risk of liver abscess formation following DEB-TACE treatment in patients with metastatic hepatic tumors. Advances in knowledge: Identification of risk factors for liver abscess formation following DEB-TACE in patients with MHT. These findings suggest the need for caution and consideration of the aforementioned risk factors on the part of interventional radiologists when designing DEB-TACE strategies and performing post-procedure patient management.

Serum LAG-3 Predicts Outcome and Treatment Response in Hepatocellular Carcinoma Patients With Transarterial Chemoembolization

BackgroundTransarterial chemoembolization (TACE) stands for the most commonly utilized therapy for hepatocellular carcinoma (HCC) worldwide. This study was to explore the potential predictive and prognostic roles of LAG-3 and PD-L1 as serum biomarkers in HCC patients underwent TACE treatment.MethodsA total of 100 HCC patients receiving TACE as well as 30 healthy controls were enrolled in the study. Serum LAG-3 and PD-L1 levels were determined at baseline and 3 day after TACE using enzyme-linked immunosorbent assay (ELISA).ResultsWe found serum levels of LAG-3 and PD-L1 were significantly elevated in HCC patients compared with healthy controls. Interestingly, patients with low pre-TACE and post-TACE levels of LAG-3 but not PD-L1 had a high probability of achieving an objective response (OR) after TACE treatment. Additionally, high pre-TACE LAG-3 level was correlated with poor disease outcome, and the patients with both high serum LAG-3 and PD-L1 level had the shorter overall survival (OS) than patients who are either PD-L1 or LAG-3 high or both PD-L1 and LAG-3 low. High pre-TACE serum LAG-3 level was positively associated with more cirrhosis pattern, advanced BCLC stage, pre-TACE alanine aminotransferase (ALT) level, and pre-TACE aspartate aminotransferase (AST) level. Furthermore, in 50 patients who underwent TACE, the serum LAG-3 level was significantly decreased at 3 day after TACE.ConclusionBoth pre-TACE and post-TACE serum LAG-3 levels could serve as powerful predictors for tumor response of TACE, and high pre-TACE serum LAG-3 level was an indicator for poor prognosis in HCC.

Transarterial chemoembolization of hepatocellular carcinoma before liver transplantation and risk of post-transplant vascular complications: a multicentre observational cohort and propensity score-matched analysis

Background Transarterial chemoembolization (TACE) in patients with hepatocellular cancer (HCC) on the waiting list for liver transplantation may be associated with an increased risk for hepatic artery complications. The present study aims to assess the risk for, primarily, intraoperative technical hepatic artery problems and, secondarily, postoperative hepatic artery complications encountered in patients who received TACE before liver transplantation. Methods Available data from HCC liver transplantation recipients across six European centres from January 2007 to December 2018 were analysed in a 1 : 1 propensity score-matched cohort (TACE versus no TACE). Incidences of intraoperative hepatic artery interventions and postoperative hepatic artery complications were compared. Results Data on postoperative hepatic artery complications were available in all 876 patients (425 patients with TACE and 451 patients without TACE). Fifty-eight (6.6 per cent) patients experienced postoperative hepatic artery complications. In total 253 patients who had undergone TACE could be matched to controls. In the matched cohort TACE was not associated with a composite of hepatic artery complications (OR 1.73, 95 per cent c.i. 0.82 to 3.63, P = 0.149). Data on intraoperative hepatic artery interventions were available in 825 patients (422 patients with TACE and 403 without TACE). Intraoperative hepatic artery interventions were necessary in 69 (8.4 per cent) patients. In the matched cohort TACE was not associated with an increased incidence of intraoperative hepatic artery interventions (OR 0.94, 95 per cent c.i. 0.49 to 1.83, P = 0.870) Conclusion In otherwise matched patients with HCC intended for liver transplantation, TACE treatment before transplantation was not associated with higher risk of technical vascular issues or hepatic artery complications.

The Efficacy of Transarterial Chemoembolization in Downstaging Unresectable Hepatocellular Carcinoma to Curative Therapy: A Predicted Regression Model

Background: Patients with hepatocellular carcinoma (HCC) outside the Milan criteria (MC) may be candidates for curative therapy after successful downstaging. However, there have been no studies that have examined the factors affecting the efficacy of transarterial chemoembolization (TACE) on downstaging. We aimed to identify the predictors of successful downstaging of unresectable HCC in patients by TACE outside the MC.Methods: We performed a retrospective study on patients with unresectable HCC outside the MC who received downstaging with TACE. Clinical and laboratory variables were recorded. We identified 101 patients with unresectable HCC who underwent initial TACE, and they formed the derivation set of this study. Thirty patients who received TACE treatment with the same selection criteria served as an external validation set. We performed multivariate logistic regression analyses to identify the variables associated with successful downstaging. Then, we created a predictive model and determined its accuracy in predicting the efficiency of TACE.Results: Of the 101 patients in the study, 26 patients (25.7%) were successfully downstaged. Multivariate analysis was performed on the number of tumors (P=0.018), portal vein tumor thrombi (PVTT) (＜0.001), the size of tumors (P=0.021), hepatitis B surface antigen (HBsAg) (P=0.014), and a-fetoprotein (AFP, P=0.027), which were considered as significant predictors of successful downstaging of HCC outside the MC. Then, we constructed the predictive model. The area under the ROC curve (AUROC) for the predictive equation was 0.908 (95% confidence interval, 0.832-0.957).Conclusions: We found in our study that the number and size of tumors, PVTT, HBsAg, and AFP are good predictors of successful downstaging of unresectable HCC in patients by TACE outside the MC.

Addition of Camrelizumab to Transarterial Chemoembolization in Hepatocellular Carcinoma With Untreatable Progression

Purpose: To evaluate the efficacy and safety of camrelizumab addition to transarterial chemoembolization (TACE) in treatment of hepatocellular carcinoma (HCC) with TACE-related untreatable progression (UP).Methods: Patients with HCC who received addition of camrelizumab due to UP after initial TACE treatment were enrolled at our institution between May 2019 and January 2021. Patients were assessed for tumor response, progression-free survival (PFS), and adverse events. Risk factors for PFS were evaluated with logistic regression analysis.Results: A total of 41 patients were included. The objective response rate and disease control rate were 24.4% and 61.0% at 2-3 months, and 12.2% and 58.5% at 6 months, respectively. The median PFS of the patients were 6 months (95% CI: 3.8 months, 8.2 months). Of the 41 patients, 23 patients received camrelizumab combined with TACE (hereafter, camrelizumab-TACE), in whom 52 combined TACE procedures were performed, with a median of 2 procedures (range, 1-6) per patient. The remaining 18 patients received camrelizumab alone due to TACE contraindications. Multivariable analysis indicated that camrelizumab-TACE was an independent prognostic factor for PFS. Subgroup analysis showed a median PFS of 8 months in the camrelizumab-TACE group and 3 months in the camrelizumab monotherapy group (P<0.001). No treatment-related mortalities occurred. Seventeen patients (41.5%) developed at least one type of adverse events after treatment with camrelizumab, with reactive cutaneous capillary endothelial proliferation (n=14, 34.1%) being the most common adverse events.Conclusions: Addition of camrelizumab to TACE offered an effective and safe treatment for HCC with UP.

Transcatheter arterial chemoembolization combined with Hippo/YAP inhibition significantly improve the survival of rats with transplanted hepatocellular carcinoma

Background This study aimed to explore the effect of inhibiting the Hippo/Yes-associated protein (YAP) signaling pathway on the outcomes of transcatheter arterial chemoembolization (TACE) in treating transplanted hepatocellular carcinoma (HCC). Methods A transplanted HCC rat model was established. Then, rats were randomly divided into four groups: Sham, TACE, verteporfin (inhibitor of Hippo/YAP), and TACE+verteporfin. Lent-OE-YAP was transfected into rats to overexpress YAP in vivo. After treatments, morphological changes, tumor weight, and the overall survival of rats in different groups were analyzed. Real-time PCR, immunohistochemistry staining, and Western blotting were used to determine the expression of factors related to the Hippo/YAP signaling pathway. Results Tumor weight and tissue lesions in the TACE and verteporfin groups were significantly reduced compared with the Sham group. Verteporfin significantly decreased tumor weight after TACE treatment. In addition, verteporfin significantly improved the overall survival of rats with transplanted HCC after TACE treatment. Compared with the Sham group, both TACE and verteporfin groups exhibited significantly decreased expression of macrophage-stimulating (MST)1, MST2, long-acting thyroid stimulator 1, transcriptional co-activator with PDZ-binding motif (TAZ), Yes-associated protein (YAP), TEA domain transcription factor (TEAD)1, TEAD2, TEAD3, and TEAD4. TACE plus verteporfin significantly enhanced the downregulation of effectors in the Hippo/YAP signaling pathway and decreased tumor size, while the overexpression of YAP exerted opposite effects. Conclusion The inhibition of the Hippo/YAP signaling pathway via verteporfin significantly improved the outcomes of TACE in treating transplanted HCC.

Efficacy and Safety of Transarterial Chemoembolization in Elderly Patients of Advanced Hepatocellular Carcinoma With Portal Vein Tumor Thrombus: A Retrospective Study

ObjectiveThe aim of the current study was to evaluate the safety and efficacy of transcatheter arterial chemoembolization (TACE) in elderly patients diagnosed as advanced hepatocellular carcinoma (HCC) accompanied with different types of portal vein tumor thrombosis (PVTT).MethodsElderly HCC patients aged 70-year-old and above from January 2015 to December 2019 were included in this retrospective study. Efficacy data including OS, PFS, DCR, and ORR and safety data were collected in the indicated groups. Outcomes of HCC patients in the TACE group were compared with those patients in the best supportive care (BSC) group. Subgroup analyses were also conducted in the patients with different types of PVTT.ResultsAmong 245 elderly HCC patients, 124 were enrolled in this study. Out of these, 50.0% (n=62) underwent BSC treatment while 50.0% (n=62) underwent TACE. There were no major differences in the baseline characteristics of the two treatment groups. TACE treatment was associated with better median OS compared with BSC alone (11.30 m vs. 7.80 m; P&lt;0.001). Subgroup analyses showed that patients with type I and type II PVTT could benefit from TACE compared with BSC, based on that OS was 14.30 m vs. 7.80 m (P=0.007) and 13.00 m vs. 8.00 m (P=0.002), respectively. The DCR in the TACE group was 62.90%, and 17.74% in the BSC group (p&lt;0.001). The proportion of ORR in TACE group was 35.48%, while 0.00% in the BSC group (p&lt;0.001). Multivariable analyses showed that patients undergoing TACE treatment had 52% lower odds of mortality compared with patients undergoing BSC treatment (HR: 0.48; 95%CI: 0.32-0.72). Similarly, the media PFS was improved following TACE treatment (7.50 m vs. 4.00 m; P&lt;0.001). TACE could significantly prolong the PFS in both type I and type II PVTT subgroups, without greatly significant improvement in type III PVTT patients (4.50 m vs. 2.70 m; P=0.103). Type III PVTT patients in the TACE group had more AEs than type I and type II PVTT patients. According to multivariable analyses, PVTT types (type III vs. type I-II) (HR: 2.18; 95%CI: 1.29-3.70; P=0.004), tumor diameter (&gt;5 cm vs. ≤5 cm) (HR: 1.94; 95%CI: 1.28-2.93; P=0.002), and treatment (TACE vs. BSC) (HR: 0.48; 95%CI: 0.32-0.72; P&lt;0.001) were independent indicators of overall survival.ConclusionsIn elderly advanced HCC patients with PVTT, palliative TACE treatment can be an accessible effective measure to improve the OS and PFS for both type I and type II PVTT patients.