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

2021 ◽  
Vol 12 ◽  
Author(s):  
Mengzhou Guo ◽  
Feng Qi ◽  
Qianwen Rao ◽  
Jialei Sun ◽  
Xiaojing Du ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transarterial Chemoembolization ◽  
Tumor Response ◽  
Objective Response ◽  
Serum Levels ◽  
High Serum ◽  
Serum Biomarkers ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Tace Treatment

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.

Safety, tolerability and efficacy of transarterial chemoembolization using anthracyclines-loaded drug eluting microspheres for treatment of patients with unresectable hepatocellular carcinoma: Pooled analyses.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 287-287
Author(s):  
Thierry De Baere ◽  
Filipe Veloso Gomes ◽  
Gontran Verset ◽  
Gerardo Tovar-Felice ◽  
Katerina Malagari ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Function ◽  
Transarterial Chemoembolization ◽  
Tumor Response ◽  
Objective Response ◽  
Progression Free Survival ◽  
Close Monitoring ◽  
Bridge To Transplant ◽  
Level Data ◽  
Drug Eluting

287 Background: Transarterial chemoembolization either with Lipiodol (cTACE) or with drug eluting microspheres (DEM-TACE) is indicated for the treatment of hepatocellular carcinoma (HCC) not amenable to curative treatments in patients with preserved liver function. Safety of TACE is becoming more important with its increased use as a bridge to transplant or downstaging to resection, but also for preservation of liver function in case of subsequent immuno-combination therapies. LifePearl microspheres is a novel DEM comprised of polyethylene-glycol with reported good safety profile and efficacy in smaller series. Our purpose was to assess safety and efficacy of TACE using anthracycline loaded LifePearl for the treatment of patients with unresectable HCC in a pooled analysis of studies with available more than 500 patient’s level data. Methods: We pooled patient level data from 5 single arm studies. Safety was assessed by close monitoring of adverse events according to CTCAE (v4.03). Tumor response was assessed, according to mRECIST and RECIST1.1 and analyzed as best overall response to account for differences in time of imaging follow-up between studies. The Kaplan-Meier method was used to estimate event rates for time to event outcomes: progression free survival (PFS), time to unTACEable progression (TTUP) and overall survival (OS) censoring patients at time of surgery or transplantation. Results: Out of 586 patients, 85.5%, 13.5% and 1.0% were Child Pugh A, B and C, respectively. BCLC stages 0, A, B and C were 13.6%, 43.4%, 41.1% and 1.9% respectively. The mean number of HCC lesions was 2.1±1.5 and mean sum of tumor diameters was 49.3±32.9mm. In 19% of patients alpha-feto protein level was > 200ng/ml. A mean of 1.9±1.3 DEM-TACEs were performed per patient. A total of 197 events were reported including 2.6 % grade 4 and 1.5% grade 5, mostly related to post-embolization syndrome. Complete response, partial response and stable disease were 60.2%, 27.1% and 7.4% respectively providing an objective response and disease control rates of 87,3% and 94,7% respectively. 10% of patients were transplanted or resected. Median OS, PFS and TTUP is indicated in the table below. OS was 89.2%, 80.2% and 69.7% at 12, 18 and 24 months respectively. Conclusions: The treatment of patients with unresectable HCC with anthracycline loaded LifePearl showed good tolerance with acceptable toxicity and high tumor response rate that translated into promising PFS, TTUP and OS. [Table: see text]

scholarly journals Circulating MicroRNA-21 and MicroRNA-122 as Prognostic Biomarkers in Hepatocellular Carcinoma Patients Treated with Transarterial Chemoembolization

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 890
Author(s):  
Filippo Pelizzaro ◽  
Romilda Cardin ◽  
Anna Sartori ◽  
Angela Imondi ◽  
Barbara Penzo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transarterial Chemoembolization ◽  
Hypoxia Inducible Factor ◽  
Progression Free Survival ◽  
Serum Levels ◽  
Elisa Test ◽  
Prognostic Biomarkers ◽  
Enzyme Linked Immunosorbent Assay ◽  
Circulating Microrna ◽  
Drug Eluting Beads

Background: MicroRNAs (miRNAs) have been proposed as biomarkers in hepatocellular carcinoma (HCC). We aim at evaluating miR-21 and miR-122 in HCC patients treated with drug-eluting beads transarterial chemoembolization (DEB-TACE) as prognostic biomarkers and investigating their correlation with hypoxia inducible factor-1α (HIF-1α) serum levels. Methods: In this retrospective study, 12 healthy subjects, 28 cirrhotics, and 54 HCC patients (tested before and four weeks after DEB-TACE) were included. Whole blood miR-21 and miR-122 levels were measured by quantitative real time (qRT)-PCR, while serum HIF-1α was assessed by an enzyme-linked immunosorbent assay (ELISA) test. Results: The highest level of miR-21 was found in cirrhotics, while HCC patients had the highest level of miR-122 (which was even higher in “viral” HCC, p = 0.006). miR-21 ratio (after/before DEB-TACE) and miR-122 below their respective cut-offs identified patients with longer progression-free survival (p = 0.0002 and p = 0.02, respectively). The combined assessment of alpha-fetoprotein and miR-21 ratio, both independent prognostic predictors, identified early progressors among patients with complete or partial radiological response. miR-21 levels positively correlated with HIF-1α before (p = 0.045) and after DEB-TACE (p = 0.035). Conclusions: miR-21 ratio and miR-122 are useful prognostic markers after DEB-TACE. miR-21 correlates with HIF-1α and probably has a role in modulating angiogenesis in HCC.

scholarly journals Lenvatinib in combination with transarterial chemoembolization for treatment of unresectable hepatocellular carcinoma (uHCC): a retrospective controlled study

2021 ◽  
Author(s):  
Zhigang Fu ◽  
Xiaowei Li ◽  
Jiaming Zhong ◽  
Xiaoxia Chen ◽  
Kunkun Cao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Adverse Events ◽  
Clinical Outcomes ◽  
Combination Treatment ◽  
Transarterial Chemoembolization ◽  
Tumor Response ◽  
Objective Response ◽  
Controlled Study ◽  
Large Sample Size ◽  
Unresectable Hepatocellular Carcinoma

Abstract Purpose To compare the efficacy and safety of combined treatment with lenvatinib and transarterial chemoembolization (TACE) versus TACE only in patients with unresectable hepatocellular carcinoma (uHCC). Methods Of the 120 patients enrolled in this study, 60 patients received treatment with TACE only, and 60 patients received TACE plus lenvatinib. We retrospectively compared the clinical outcomes including overall survival (OS), progression-free survival (PFS), and tumor response between the two groups. Both PFS and tumor response were based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Adverse events were analyzed to assess the safety profiles. Results The 1-year and 2-year OS rates were significantly higher in the TACE + lenvatinib group (88.4% and 79.8%) than that in the TACE group (79.2% and 49.2%, p = 0.047). A similar PFS benefit was observed in the TACE + lenvatinib group (1-y PFS rate: 78.4% vs. 64.7%, 2-y PFS rate: 45.5% vs. 38.0%, p < 0.001). The best overall objective response rate (ORR) was also better with TACE + lenvatinib treatment (ORR: 68.3% vs. 31.7%, p < 0.001) and disease control rate (DCR) numerically increased in the TACE + lenvatinib treatment (93.3% vs. 86.7%, p = 0.224). Patients’ liver function remained comparable to baseline in the TACE + lenvatinib group. The most common adverse events were decreased albumin (55.0%), hypertension (48.3%) and decreased platelet count (46.7%) in the TACE + lenvatinib group. Conclusions Combination treatment with TACE and lenvatinib may significantly improve clinical outcomes over TACE monotherapy with a manageable safety profile for unresectable HCC. The efficacy of the combination treatment should be validated in prospective studies with a large sample size. Graphical abstract

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

2021 ◽  
Author(s):  
Yanqiao Ren ◽  
Ziyi Liu ◽  
Joyman Makamure ◽  
Xuefeng Kan ◽  
Songlin Song ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Adverse Events ◽  
Transarterial Chemoembolization ◽  
Objective Response ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Free Survival ◽  
Endothelial Proliferation ◽  
Tace Group ◽  
Tace Treatment

Abstract 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.

scholarly journals Sequential transarterial chemoembolization and early radiofrequency ablation improves clinical outcomes for early-intermediate hepatocellular carcinoma in a 10-year single-center comparative study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Liangliang Yan ◽  
Yanqiao Ren ◽  
Kun Qian ◽  
Xuefeng Kan ◽  
Hongsen Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Radiofrequency Ablation ◽  
Combination Therapy ◽  
Clinical Outcomes ◽  
Transarterial Chemoembolization ◽  
Response Rate ◽  
Multivariable Analysis ◽  
Complication Rates ◽  
Tace Treatment

Abstract Background Transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) are effective treatment methods for unresectable hepatocellular carcinoma (HCC). However, there is still a lack of clinical research on whether early sequential RFA, compared with late combination therapy, can improve the long-term efficacy of initial TACE treatment. Methods This retrospective study investigated a cohort of patients who underwent combination therapy using TACE and RFA (TACE followed by RFA) from January 2010 to January 2020 at our medical centre. A total of 96 patients underwent TACE combined with early RFA (usually during the first hospitalization), which was called TACE + eRFA. Thirty-four patients received 1–2 palliative TACE treatments first and then underwent TACE treatment combined with late RFA (TACE + lRFA). All patients continued to receive palliative TACE treatments after intrahepatic lesion progression until reaching intolerance. The overall survival (OS) rate, time to tumour progression (TTP), tumour response rate and major complication rates were compared between the two groups. Results There were significant differences in the median OS (46 months vs 33 months; P = 0.013), median TTP (28 months vs 14 months; P < 0.00), objective response rate (ORR) (89.6% vs 61.8%, P = 0.000) and disease control rate (DCR) (94.8% vs 73.5% P = 0.002) between the two groups. Multivariable analysis revealed that the Barcelona Clinic Liver Cancer stage was an independent risk factor for OS. Meanwhile, multivariable analysis revealed that TACE + eRFA was associated with an enhanced TTP. Conclusion Early sequential RFA treatment in patients with early-intermediate HCC can improve local tumour control and clinical outcomes while reducing the frequency of TACE treatment. In clinical practice, in HCC patients initially treated with TACE, it is recommended to combine RFA as soon as possible to obtain long-term survival.

scholarly journals Anti-phosphatidylserine/prothrombin Complex Antibodies in Patients With Cutaneous Vasculitis: Possible Involvement in the Pathogenesis

2020 ◽  
Author(s):  
Yuto Tamura ◽  
Tamihiro Kawakami ◽  
Yupeng Dong ◽  
Miku Yoshinari ◽  
Yuka Nishibata ◽  
...  
Keyword(s):  
Vascular Endothelium ◽  
Systemic Vasculitis ◽  
Serum Levels ◽  
Cutaneous Vasculitis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Iga Vasculitis ◽  
Skin Involvement ◽  
Wild Type ◽  
Significant Difference

Abstract Objective. It was previously demonstrated that cutaneous vasculitis, including IgA vasculitis and cutaneous arteritis (CA), is associated with the presence of IgM antibodies (Abs) against the phosphatidylserine/prothrombin complex (PS/PT). Recently, novel enzyme-linked immunosorbent assay kits for the detection of IgG and IgM anti-PS/PT (aPS/PT) Abs have become commercially available.Methods. The prevalence of serum IgG and IgM aPS/PT Abs in both cutaneous and systemic vasculitis was determined using these kits. In addition, to examine whether aPS/PT Abs were involved in the pathogenesis of cutaneous vasculitis, inbred wild-type rats were intravenously administered with a rat IgM class aPS/PT monoclonal Ab established previously or with rat immunoglobulins as controls. To express PS on the surface of vascular endothelium, these rats were given a subcutaneous injection of cell-free histones (250 µg/ml, 300 µl/site) 2 hours in advance. Results. Serum IgM aPS/PT Ab levels were elevated in patients with systemic vasculitis with skin involvement and CA compared to those in patients with systemic vasculitis without skin involvement and healthy controls. There was no significant difference in the serum levels of IgG aPS/PT Abs between the patients and healthy controls. Correspondingly, inbred wild-type rats intravenously administered with the aPS/PT monoclonal IgM Ab after appropriate priming—subcutaneous histone injection—developed cutaneous vasculitis. Some rats given rat IgM instead of the aPS/PT monoclonal Ab also developed cutaneous vasculitis, whereas vasculitis did not occur in rats given IgG or only priming by histones. Conclusion. IgM aPS/PT Abs could be involved in the pathogenesis of cutaneous vasculitis.

scholarly journals Low Serum Melatonin Levels Prior to Liver Transplantation in Patients with Hepatocellular Carcinoma are Associated with Lower Survival after Liver Transplantation

2019 ◽  
Vol 20 (7) ◽  
pp. 1696
Author(s):  
Leonardo Lorente ◽  
Sergio Rodriguez ◽  
Pablo Sanz ◽  
Pedro Abreu-González ◽  
Agustín González-Rivero ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Antioxidant Capacity ◽  
Total Antioxidant Capacity ◽  
Serum Levels ◽  
High Serum ◽  
Published Data ◽  
Lower Serum ◽  
Total Antioxidant ◽  
One Year

Melatonin administration has been associated with different benefits in animals and patients suffering from liver diseases. However, there is no published data about circulating melatonin levels in patients with hepatocellular carcinoma (HCC) who underwent liver transplantation (LT). Thus, the objective of this observational and retrospective study was to determine whether patients with HCC with lower serum melatonin levels prior to LT have a higher risk of one-year mortality after LT. We measured serum levels of melatonin, malondialdehyde (to assess lipid peroxidation), and total antioxidant capacity (to assess antioxidant state) before LT. One-year surviving LT patients (n = 129) showed higher serum levels of melatonin (p = 0.001) and total antioxidant capacity (p = 0.001) and lower serum levels of malondialheyde (p = 0.01) than non-surviving LT patients (n = 16). Logistic regression analysis showed that high serum melatonin levels prior to LT were associated with lower one-year LT mortality (odds ratio = 0.525; 95% confidence interval (CI) = 0.331–0.834; p = 0.006). We found an association between serum levels of melatonin with serum levels of malondialheyde (rho = −0.22; p = 0.01) and total antioxidant capacity (rho = 0.21; p = 0.01). Thus, the novel findings of our study were the association between high serum melatonin levels prior to LT and survival at first year after LT and the association between serum levels of melatonin with malondialheyde and total antioxidant capacity.

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