Treatment For Intermediate-stage Hepatocellular Carcinoma Research Articles

Comprehensive Bioinformatics Analysis and Machine Learning of TTK as a Transhepatic Arterial Chemoembolization Resistance Target in Hepatocellular Carcinoma.

Transhepatic arterial chemoembolization (TACE) is the standard treatment for intermediate-stage hepatocellular carcinoma (HCC). However, a significant proportion of patients are non-responders or poor responders to TACE. Therefore, our aim is to identify the targets of TACE responders or non-responders. GSE104580 was utilized to identify differentially expressed genes (DEGs) in TACE responders and non-responders. Following the protein-protein interaction (PPI) analysis, hub genes were identified using the MCC and MCODE plugins in Cytoscape software, as well as LASSO regression analysis. Gene set enrichment analysis (GSEA) was performed to investigate potential mechanisms. Subsequently, the hub genes were validated using data from The Cancer Genome Atlas (TCGA), the Cancer Cell Line Encyclopedia (CCLE), and The Human Protein Atlas (HPA) database. To evaluate the clinical significance of the hub genes, Kaplan-Meier (KM) survival and Cox regression analysis were employed. A total of 375 DEGs were identified, with 126 remaining following PPI analysis, and TTK, a dual-specificity protein kinase associated with cell proliferation, was ultimately identified as the hub gene through multiple screening methods. Data analysis from TCGA, CCLE, and HPA databases revealed elevated TTK expression in HCC tissues. GSEA indicated that the cell cycle, farnesoid X receptor pathway, PPAR pathway, FOXM1 pathway, E2F pathway, and ferroptosis could be potential mechanisms for TACE non-responders. Analysis of immune cell infiltration showed a significant correlation between TTK and Th2 cells. KM and Cox analysis suggested that HCC patients with high TTK expression had a worse prognosis. TTK may play a pivotal role in HCC patients' response to TACE therapy and could be linked to the prognosis of these patients.

DEB-TACE versus cTACE for unresectable HCC with B1-type bile duct invasion after successful biliary drainage: A propensity score matching analysis.

Transarterial chemoembolization (TACE) is the standard treatment for intermediate-stage hepatocellular carcinoma (HCC). Given the lack of specific recommendations for conventional TACE (cTACE) and drug-eluting bead TACE (DEB-TACE) in patients having unresectable HCC with tumor infiltrating the common hepatic duct or the first-order branch of the bile ducts (B1-type bile duct invasion; B1-BDI) after biliary drainage, we retrospectively compared the safety and efficacy of DEB-TACE with cTACE in this patient population. Using data from five tertiary medical centers (January 2017-December 2021), we compared complications, overall survival (OS), time to progression (TTP), and tumor response rate between patients having unresectable HCC with B1-BDI who underwent DEB-TACE or cTACE after successful biliary drainage. X-tile software calculated the pre-TACE total bilirubin (TBil) cutoff value, indicating optimal timing for sequential TACE after drainage. Propensity score matching (PSM) was performed. The study included 108 patients with unresectable HCC (B1-BDI) who underwent DEB-TACE and 114 who received cTACE as initial treatment. After PSM (n = 53 for each group), the DEB-TACE group had a longer TTP (8.9 vs. 6.7 months, p = 0.038) and higher objective response rate (64.2% vs. 39.6%, p = 0.011) than did the cTACE group, although OS was comparable (16.7 vs. 15.3 months, p = 0.115). The DEB-TACE group exhibited fewer post-procedural increments in the mean albumin-bilirubin score, TBil, and alanine aminotransferase (ALT), along with a significantly lower incidence of serious adverse events within 30 days (hepatic failure, ALT increase, and TBil increase) than the cTACE group (all p < 0.05). The pre-TACE TBil cutoff value was 99 μmol/L; patients with higher values (>99 μmol/L) had poorer OS in both groups (p < 0.05). DEB-TACE is safe and effective after successful biliary drainage in unresectable HCC with B1-BDI, potentially better than cTACE in terms of liver toxicity, TTP, and ORR. Lowering TBil below 99 μmol/L through successful drainage may create ideal conditions for sequential TACE.

Liver abscess and tracheal fistula induced by transcatheter arterial chemoembolization for hepatocellular carcinoma: A case report

BACKGROUND Transarterial chemoembolization (TACE) is a standard treatment for intermediate-stage hepatocellular carcinoma (HCC). The complications of TACE include biliary tract infection, liver dysfunction, tumor lysis syndrome, biloma, partial intestinal obstruction, cerebral lipiodol embolism, etc . There are few reports about tracheal fistula induced by TACE. CASE SUMMARY A 42-year-old man came to our hospital with cough and expectoration for 1 mo after TACE for HCC. Laboratory test results showed abnormalities of albumin, hemoglobin, prothrombin time, C-reactive protein, D-dimer, and prothrombin. Culture of both phlegm and liver pus revealed growth of Citrobacter flavescens . Computed tomography showed infection in the inferior lobe of the right lung and a low-density lesion with gas in the right liver. Liver ultrasound showed that there was a big hypoechoic liquid lesion without blood flow signal. Drainage for liver abscess by needle puncture under ultrasonic guidance was performed. After 1 mo of drainage and anti-infection therapy, the abscess in the liver and the infection in the lung were reduced obviously, and the symptom of expectoration was relieved. CONCLUSION Clinicians should be alert to the possibility of complications of liver abscess and tracheal fistula after TACE for HCC. Drainage for liver abscess by needle puncture under ultrasonic guidance could relieve the liver abscess and tracheal fistula.

REPLACE: A phase III, randomized, open-label trial to evaluate the safety and efficacy of regorafenib and pembrolizumab versus locoregional therapy (LRT) with transarterial chemoembolization (TACE) or transarterial radioembolization (TARE), for the first-line treatment of intermediate-stage hepatocellular carcinoma (HCC) with beyond up-to-7 criteria.

TPS4200 Background: Intermediate-stage HCC represents a heterogeneous population, posing unique challenges for therapeutic management. With the advent of effective systemic therapies for unresectable HCC, the treatment landscape for intermediate-stage extends beyond LRT, particularly in patients with high tumor burden. The growing evidence about the benefit of systemic therapy in intermediate-stage HCC led to the inclusion in some recent guidelines of systemic therapy as the first choice of treatment in TACE-unsuitable patients with intermediate-stage HCC. Despite these recommendations, no randomized clinical trial has been published comparing LRT with TACE/TARE versus systemic therapy in patients with intermediate-stage HCC and high tumor burden. Methods: REPLACE is a phase III, multicenter, randomized, open-label trial that will compare the efficacy and safety of LRT with TACE/TARE versus systemic therapy, for the first-line treatment of intermediate-stage HCC with beyond up-to-7 criteria. Eligible participants will be randomized 1:1 to receive regorafenib (90 mg orally q.d. on days 1 to 21 of a 4-week cycle), and pembrolizumab (400 mg i.v. on day 1 of a 6-week cycle) or LRT with TACE or TARE, and will be stratified according to geographic region (Asia vs. non-Asia), ECOG Performance Status (0 vs 1) and Albumin-Bilirubin (ALBI) grade (1 vs 2). Patients must have intermediate-stage HCC with beyond up-to-seven criteria (Up-to-7 criteria = largest tumor diameter (cm) + number of tumors ≤7), measurable disease per RECIST 1.1, disease not amenable to curative treatment but amenable to LRT with TACE or TARE, no prior systemic or LRT for HCC, except for successful resection and/or ablation completed ≥ 6 months prior to randomization. Patients will be treated until progressive disease, unacceptable toxicity, or other treatment discontinuation criteria is met. The primary endpoint is progression free survival (PFS), assessed locally by the Investigator using mRECIST for HCC. Secondary endpoints include PFS assessed locally by the Investigator using RECIST 1.1; PFS centrally assessed using mRECIST and RECIST 1.1; overall survival; overall response rate according to RECIST v.1.1 and mRECIST based on the Investigator’s and central assessment; time to unTACEable progression; duration of response; safety and tolerability of the trial treatments, and patient reported outcomes for health-related quality of life. The estimated enrollment is 496 patients from approximately 14 countries. Recruitment started in October 2023 and is currently ongoing. Clinical trial information: NCT04777851 .

Safety, efficacy, and survival of different transarterial chemoembolization techniques in the management of unresectable hepatocellular carcinoma: a comparative single-center analysis

PurposeTransarterial chemoembolization (TACE) has become the standard of care for the treatment of intermediate-stage hepatocellular carcinoma (HCC). However, current clinical practice guidelines lack consensus on the best selection of a specific TACE technique. This study aims to compare safety, tumor response, and progression-free survival (PFS) of conventional TACE (cTACE), drug-eluting bead TACE (DEB-TACE), and degradable starch microsphere TACE (DSM-TACE).MethodsThis retrospective study included n = 192 patients with HCC who underwent first TACE with unbiased follow-up at 4–6 weeks at our center between 2008 and 2021. Eligibility for TACE was BCLC intermediate stage B, bridging/down-staging (B/D) to liver transplantation (LT), or any other stage when patients were not suitable for resection, LT, local ablation, or systemic therapy. Patients were grouped into three cohorts (n = 45 cTACE, n = 84 DEB-TACE, n = 63 DSM-TACE), and further categorized by TACE indication (B/D or palliative). Liver function and adverse events, response assessed by the modified response evaluation criteria in solid tumors (mRECIST) 4–6 weeks post-TACE and PFS were analyzed.ResultsThere were no significant differences in age, gender distribution, BCLC stage, or etiology of liver disease among the three TACE groups, even in the B/D or palliative subgroups. DEB-TACE induced slight increases in bilirubin in the palliative subgroup and in lactate dehydrogenase in the entire cohort 4–6 weeks post-TACE, and more adverse events in the palliative subgroup. DEB-TACE and DSM-TACE showed significantly higher disease control rates (complete and partial response, stable disease) compared to cTACE, especially in the B/D setting (p < 0.05). There was no significant difference in PFS between the groups [median PFS (months): cTACE, 10.0 vs. DEB, 7.0 vs. DSM, 10.0; p = 0.436].ConclusionOur study provides valuable perspectives in the decision-making for a specific TACE technique: DEB-TACE and DSM-TACE showed improved tumor response. DEB-TACE showed a prolonged impact on liver function and more side effects, so patients with impaired liver function should be more strictly selected, especially in the palliative subgroup.

Child–Pugh grade deterioration stratified by the etiology after transcatheter arterial chemoembolization as initial treatment for hepatocellular carcinoma

Transcatheter arterial chemoembolization (TACE) is a standard treatment for intermediate-stage hepatocellular carcinoma (HCC). However, TACE can cause deterioration of liver functions. We aimed to identify the factors that influence deterioration of liver function after TACE. We retrospectively analyzed 262 patients who underwent TACE as initial treatment for HCC with Child–Pugh grade A. We divided them into three groups stratified by the etiology of underlying liver disease. Patients were classified into hepatitis B virus (HBV) group, hepatitis C virus (HCV) group, and non-HBV / non-HCV (NBNC) group. Liver functions at one month after TACE and time to Child–Pugh grade B or C were compared between the three groups. The HBV, HCV and NBNC groups contained 23, 123 and 116 patients, respectively. The decline in albumin level after TACE was significantly higher in NBNC group than other groups (p = 0.02). NBNC group showed a shorter time to Child–Pugh grade deterioration compared with HBV group and HCV group (p < 0.001). Multivariate Cox regression analysis showed that NBNC group was a significant factor for Child–Pugh grade deterioration (Hazard ratio 3.74, 95% confidence interval 1.89–7.40, p < 0.001). These results revealed that liver functions worsened most remarkably in NBNC group after TACE.

Identification of the key genes and mechanisms associated with transcatheter arterial chemoembolisation refractoriness in hepatocellular carcinoma.

Transcatheter arterial embolisation (TACE) is the primary treatment for intermediate-stage hepatocellular carcinoma (HCC) patients while some HCC cases have shown resistance to TACE. To investigate the key genes and potential mechanisms correlated with TACE refractoriness in HCC. The microarray datasets of TACE-treated HCC tissues, HCC and non-HCC tissues were collected by searching multiple public databases. The respective differentially expressed genes (DEGs) were attained via limma R package. Weighted gene co-expression network analysis was employed for identifying the significant modules related to TACE non-response. TACE refractoriness-related genes were obtained by intersecting up-regulated TACE-associated and HCC-associated DEGs together with the genes in significant modules related to TACE non-response. The key genes expression in the above two pairs of samples was compared respectively via Wilcoxon tests and standard mean differences model. The prognostic value of the key genes was evaluated by Kaplan-Meier curve. Multivariate analysis was utilised to investigate the independent prognostic factor in key genes. Single-cell RNA (scRNA) sequencing analysis was conducted to explore the cell types in HCC. TACE refractoriness-related genes activity was calculated via AUCell packages. The CellChat R package was used for the investigation of the cell-cell communication between the identified cell types. HCC tissues of TACE non-responders (n = 66) and TACE responders (n = 81), HCC (n = 3941) and non-HCC (n = 3443) tissues were obtained. The five key genes, DLG associated protein 5 (DLGAP5), Kinesin family member 20A (KIF20A), Assembly factor for spindle microtubules (ASPM), Kinesin family member 11 (KIF11) and TPX2 microtubule nucleation factor (TPX2) in TACE refractoriness-related genes, were identified. The five key genes were all up-regulated in the TACE non-responders group and the HCC group. High expression of the five key genes predicted poor prognosis in HCC. Among the key genes, TPX2 was an independent prognostic factor. Four cell types, hepatocytes, embryonic stem cells, T cells and B cells, were identified in the HCC tissues. The TACE refractoriness-related genes expressed primarily in hepatocytes and embryonic stem cells. Hepatocytes, as the providers of ligands, had the strongest interaction with embryonic stem cells that provided receptors. Five key genes (DLGAP5, KIF20A, ASPM, KIF11 and TPX2) were identified as promoting refractory TACE. Hepatocytes and embryonic stem cells were likely to boost TACE refractoriness.

Efficacy of Lenvatinib in Combination With PD-1 Monoclonal Antibody and Interventional Treatment for Intermediate-Stage Hepatocellular Carcinoma: Impact on Serum Vascular Endothelial Growth Factor and Matrix Metalloproteinase-9 Levels: A Retrospective Study.

Objectives: To scrutinize the therapeutic efficiency and safety profile of lenvatinib, accompanied by the programmed cell death protein-1 (PD-1) monoclonal antibody, and interventional treatment in managing intermediate-stage hepatocellular carcinoma. Methods: Retrospective analysis was performed on clinical data from 93 patients suffering from intermediate to advanced hepatocellular carcinoma, treated at our institution from May 2018 to April 2020. Patients were divided based on the therapeutic regimen: 43 cases constituted the control group receiving lenvatinib plus transhepatic artery chemoembolization (TACE), while the remaining 50 cases in the study group were managed with lenvatinib, PD-1 monoclonal antibody, and TACE. Outcome measures included therapeutic efficacy, tumor markers (carcinoembryonic antigen [CEA], alpha-fetoprotein [AFP], α-L-fucosidase [AFU], carbohydrate antigen 199 [CA199]), immune response indices (CD3+, CD4+, CD8+, CD4+/CD8+ ratio), pertinent cytokine levels (vascular endothelial growth factor [VEGF], matrix metalloproteinase-9 [MMP-9], basic fibroblast growth factor [aFGF], acidic fibroblast growth factor [bFGF]), quality of life (as per Quality of Life Assessment Scale for Cancer Patients [QOL-LC] scores), adverse effects, and survival rates. Results: The study group exhibited a significantly enhanced total effective rate compared to the control group (74.00% vs 53.49%, P < .05). Post-treatment levels of CEA, AFP, AFU, CA199, CD8+, VEGF, MMP-9, aFGF, and bFGF were notably lower in both groups, particularly in the study group. Contrastingly, CD3+, CD4+, CD4+/CD8+ratios, and QOL-LC scores were substantially elevated in the study group (P < .05). Adverse reaction prevalence was analogous between 2 groups (27.91% vs 26.00%; P > .05). Moreover, the study group reported significantly higher 1-, 2-, and 3-year survival rates than the control group (P < .05). Conclusion: The combined use of lenvatinib, PD-1 monoclonal antibody, and interventional treatment for intermediate to advanced hepatocellular carcinoma may have a definitive therapeutic efficacy. This regimen is effective in reducing tumor marker levels, enhancing immune function, modulating VEGF, MMP-9, and other related cytokine levels, and improving patients' quality of life without significantly augmenting adverse effects. This treatment paradigm also contributes to increased survival rates and promises favorable prognosis.

Proton Beam Therapy for HCC Exceeding up-to-Seven Criteria

Whilst standard treatment for intermediate-stage hepatocellular carcinoma (HCC) is transcatheter arterial chemoembolization (TACE), those exceeding "up-to-seven" criteria don't respond as such as those within, and systemic therapy is suggested to be more beneficial. This is sought to be both because of the limited efficacy of TACE and its hepatic toxicity. Proton beam therapy (PBT) offers high local control and low toxicity rates, and we hypothesize that the same can be said in this patient group also. We here present the outcome of PBT for primary HCC exceeding "up-to-seven" criteria. Primary HCC treated with PBT between 2010 and 2018 were extracted from an all-in treatment database and retrospectively reviewed. (Maximum diameter of the largest tumor in centimeters) + (tumor count) > 7 was considered as exceeding "up-to-seven" criteria. Local recurrence was defined as tumor re-enlargement or the appearance of arterial phase hyperenhancement. Adverse events were evaluated by CTCAE v5.0. Overall survival and recurrence-free survival were determined by the Kaplan-Meier method, and local recurrence was analyzed as cumulative incidence with death as a competing risk. All statistical analyses were done using R. Out of 202 primary cases, 79 exceeded the "up-to-seven" criteria. The median tumor diameter was 8.0 cm (range 3.1 - 20 cm) and macroscopic vascular invasion (MVI) was observed in 26 cases. For tumor count, 36 were solitary, 28 were between 2 - 3, and 15 had 4 or more. According to the modified ALBI grade, 38 were grade 1, 18 were grade 2a and 23 were 2b. The prescribed dose was 66 Gy / 10 Fr for 6, 72.6 Gy / 22 Fr for 60, 74 Gy / 37 Fr for 12 and 60 Gy / 15 Fr for one case after relative biological effect weighting of 1.1. With a median follow-up period of 33 months (IQR 15 - 57 months), 2-year overall survival was 62% (95% C.I. 50 - 72%) and median survival time was 37 months (95% C.I. 30 - 52 months). 2-year recurrence-free survival and local recurrence rate were 42% (95% C.I. 30 - 53%) and 8% (95% C.I. 3 - 15%) respectively. Cox regression analysis revealed modified ALBI grade as the only significant risk factor for survival (hazard ratio 1.80, 95% C.I. 1.27 - 2.55, p = 0.0010) among age, sex, alpha-fetoprotein level, MVI, tumor count, and size. Other than one case of early death (2 weeks after treatment) with an unknown causal relationship, there were no adverse events of grade 4 or higher observed. PBT for primary HCC exceeding "up-to-seven" criteria appears to be safe and effective. Local control of intrahepatic lesions may be beneficial even in intermediate-stage cases, while results of this study suggests that suppression of out-of-field recurrence is required for further survival prolongment.

Prognosis of Patients with Hepatocellular Carcinoma Treated with Transarterial Chemoembolization(MC-hccAI 001): Development and Validation of the ALFP Score.

Transarterial chemoembolization (TACE) is the recommended first-line treatment for intermediate-stage Hepatocellular carcinoma (HCC) patients. However, predicting the survival of HCC patients receiving TACE remains challenging. In this retrospective study, we analyzed a total of 1805 HCC patients who received TACE. The patients were randomly divided into a training set (n = 1264) and a validation set (n = 541). We examined various prognostic factors within the training set and developed a simple ALFP (ALBI grade, AFP, and Prothrombin time) score, which was subsequently validated using the independent validation set. Our multivariate analysis revealed that baseline ALBI grade 2 or 3, AFP ≥ 100 ng/mL, and PT > 13.1 s were independent unfavorable prognostic factors for HCC patients receiving TACE (p < 0.05). Based on these findings, we constructed the ALFP score, which assigns 1 point each for ALBI grade 2 or 3, AFP ≥ 100 ng/mL, and PT > 13.1 s. The score has a range of 0 to 3, and higher scores are associated with poorer outcomes. The median overall survival (OS) varied significantly among different ALFP score groups, both in the training set and the validation set (p < 0.001). We further examined the ALFP score in subgroups based on tumor diameter and the number of intrahepatic lesions. In each subgroup, higher ALFP scores were consistently associated with lower OS (p < 0.05). Our study confirms the prognostic value of the ALFP score in predicting the survival of HCC patients undergoing TACE. The score incorporates easily obtainable baseline parameters and provides a simple and practical tool for risk stratification and treatment decision-making in HCC patients.

Liver resection versus transarterial chemoembolisation for the treatment of intermediate hepatocellular carcinoma: a systematic review and meta-analysis.

Transarterial chemoembolisation (TACE) is the primary treatment for intermediate-stage hepatocellular carcinoma (HCC), according to the updated Barcelona Clinic Liver Cancer (BCLC) staging system. Although growing evidence favours liver resection (LR) over TACE for intermediate-stage HCC, the best treatment option remains controversial. This meta-analysis aimed to compare the overall survival (OS) after LR versus TACE for intermediate-stage HCC. A comprehensive literature review of PubMed, Embase, Cochrane Library, and Web of Science was performed. Studies that compared the efficacy of LR and TACE in patients with intermediate (BCLC stage B) HCC were selected. According to the recent updated BCLC classification, intermediate stage of HCC was defined as follows: (a) four or more HCC nodules of any size, or (b) two or three nodules, but if at least one tumour is larger than 3cm. The main outcome was OS, expressed as the hazard ratio. Nine eligible studies of 3355 patients were included in the review. The OS of patients who underwent LR was significantly longer than that of patients who underwent TACE (hazard ratio=0.52; 95% CI: 0.39-0.69; I2=79%). Prolonged survival following LR was confirmed after sensitivity analysis of five studies using propensity score matching (HR=0.45; 95% CI: 0.34-0.59; I2=55%). Patients with intermediate-stage HCC who underwent LR had a longer OS that those who underwent TACE. The role of LR in patients with BCLC stage B should be clarified in future randomised controlled trials.

Treatment Strategy for Intermediate-Stage Hepatocellular Carcinoma: Transarterial Chemoembolization, Systemic Therapy, and Conversion Therapy

Transarterial chemoembolization (TACE) has been standard treatment for intermediate-stage hepatocellular carcinoma (HCC). However, all intermediate-stage HCC patients did not benefit from TACE treatment because intermediate-stage HCC encompasses a wide variety of HCCs. Owing to remarkable progress in systemic therapy, including molecular-targeted therapy for advanced-stage HCC, the standard treatment of HCC has recently shifted to systemic therapy. However, it remains controversial as to which treatment should be initially performed for intermediate-stage HCC. In addition, although curative treatment can be considered when the tumor shrinks, the timing of conversion therapy remains uncertain. This review summarizes the advances of HCC treatment and discusses treatment strategies for intermediate-stage HCC.

Efficacy of dexamethasone and N-acetylcysteine combination in preventing post-embolization syndrome after transarterial chemoembolization in hepatocellular carcinoma

Conventional transarterial chemoembolization (cTACE) is the current standard treatment for intermediate-stage hepatocellular carcinoma (HCC). Post-embolization syndrome (PES) is complex clinical syndrome that presents as fever, abdominal pain, nausea, and vomiting. Either dexamethasone (DEXA) or N-acetylcysteine (NAC) is used to prevent PES; however, the synergistic effect of their combined therapy for preventing PES and liver decompensation has not been determined. To evaluate the efficacy of DEXA and NAC combination in preventing PES and liver decompensation after cTACE. Patients with Barcelona Clinic Liver Cancer stage A or B HCC who were scheduled for TACE were prospectively enrolled. All patients were randomly stratified to receive NAC and DEXA or placebo. The dual therapy (NAC + DEXA) group received intravenous administration of 10 mg DEXA every 12 h, NAC 24 h prior to cTACE (150 mg/kg/h for 1 h followed by 12.5 mg/kg/h for 4 h), and a continuous infusion of 6.25 mg/h NAC plus 4 mg DEXA every 12 h for 48 h after cTACE. The placebo group received an infusion of 5% glucose solution until 48 h after procedure. PES was defined by South West Oncology Group toxicity code grading of more than 2 that was calculated using incidence of fever, nausea, vomiting, and pain. One-hundred patients were enrolled with 50 patients in each group. Incidence of PES was significantly lower in the NAC + DEXA group compared with in the placebo group (6% vs 80%; P < 0.001). Multivariate analysis showed that the dual treatment is a protective strategic therapy against PES development [odds ratio (OR) = 0.04; 95% confidence interval (CI): 0.01-0.20; P < 0.001). Seven (14%) patients in the placebo group, but none in the NAC + DEXA group, developed post-TACE liver decompensation. A dynamic change in Albumin-Bilirubin score of more than 0.5 point was found to be a risk factor for post-TACE liver decompensation (OR = 42.77; 95%CI: 1.01-1810; P = 0.049). Intravenous NAC + DEXA administration ameliorated the occurrence of PES event after cTACE in patients with intermediate-stage HCC.

Achievement of cancer- and treatment-free status by atezolizumab plus bevacizumab combined with or without curative conversion in patients with transarterial chemoembolization-unsuitable, intermediate-stage hepatocellular carcinoma: A multicenter cohort study.

535 Background: Atezolizumab plus bevacizumab therapy is extremely effective in the treatment of intermediate-stage hepatocellular carcinoma (HCC), with a response rate of 44%, as reported in the IMbrave150 trial. Tumor shrinkage is achieved, and cancer- and treatment-free status is possible in many cases using curative conversion with resection, ablation, or selective transarterial chemoembolization (TACE). This concept, i.e., curative conversion by combining systemic therapy and locoregional therapy, has not been reported before. This multicenter study was conducted to clarify the value of curative conversion in intermediate-stage HCC meeting TACE-unsuitable criteria. Methods: This study included 110 consecutive Child-Pugh A patients who received atezolizumab plus bevacizumab as first-line treatment for unresectable and TACE-unsuitable intermediate-stage HCC at seven centers in Japan. Cancer-free rate, treatment-free rate, time to cancer-free status, change in liver function, efficacy in positron emission tomography (PET)-positive HCC, recurrence-free survival (RFS), and overall survival (OS) were assessed in patients who achieved cancer-free status using resection, ablation, selective TACE, or atezolizumab plus bevacizumab alone. Results: Cancer-free status was achieved in 38 patients (35%) (median observation period: 17. 7 months). The modalities of curative conversion were as follows: resection, 7; ablation (including patients who underwent ablation after TACE), 13; and selective TACE (including lenvatinib-TACE sequential therapy), 15. Three patients achieved cancer-free status with only atezolizumab plus bevacizumab therapy. Among the 38 cancer-free patients, 24 achieved treatment-free status. RF5 was 31.8 months (95% confidence interval, 30.5-33.0), and two patients experienced recurrence after reaching cancer-free status. Regarding OS, there were no deaths in any of the groups, and excellent outcomes were obtained. The albumin-bilirubin score did not deteriorate after locoregional therapy or resection. Of seven PET-positive patients who achieved cancer-free status, five achieved treatment-free status. Conclusions: The curative conversion rate (cancer-free rate) in patients treated with atezolizumab plus bevacizumab as the preceding therapy for unresectable and TACE-unsuitable intermediate-stage HCC was 35%. Overall, 22% of patients achieved treatment-free status. Thus, achieving cancer-free and/or treatment-free status should be a therapeutic goal for patients with intermediate-stage HCC without vascular invasion or extrahepatic spread. Clinical trial information: NCT03434379 .

Achievement of Complete Response and Drug-Free Status by Atezolizumab plus Bevacizumab Combined with or without Curative Conversion in Patients with Transarterial Chemoembolization-Unsuitable, Intermediate-Stage Hepatocellular Carcinoma: A Multicenter Proof-Of-Concept Study

Introduction: Atezolizumab plus bevacizumab therapy is extremely effective in the treatment of intermediate-stage hepatocellular carcinoma (HCC), with a response rate of 44%, as reported in the IMbrave150 trial. When tumor shrinkage is obtained, achieving complete response (CR) is possible in many cases using curative conversion with resection, ablation, or superselective transarterial chemoembolization (TACE) with curative intent. This concept, i.e., curative conversion by combining systemic therapy and locoregional therapy, has not been reported before. This multicenter proof-of-concept study was conducted to show the value of curative conversion in immunotherapy-treated intermediate-stage HCC meeting TACE-unsuitable criteria. Methods: This study included 110 consecutive Child-Pugh A patients who received atezolizumab plus bevacizumab as first-line treatment for unresectable and TACE-unsuitable intermediate-stage HCC at seven centers in Japan. CR rate, drug-free rate, time to CR, change in liver function, efficacy in positron emission tomography (PET)-positive HCC, progression-free survival (PFS), and overall survival (OS) were assessed in patients who achieved CR using resection, ablation, superselective TACE with curative intent following atezolizumab plus bevacizumab or atezolizumab plus bevacizumab alone. Results: Clinical or pathological CR was achieved in 38 patients (35%) (median observation period: 21.2 months). The modalities of curative conversion in 35 patients were as follows: resection, 7; ablation, 13; and superselective TACE, 15. Three patients achieved clinical CR with atezolizumab plus bevacizumab therapy alone. Among the 38 CR patients, 25 achieved drug-free status. PFS was not reached, and 3 patients experienced recurrence after reaching CR. Regarding OS, there were no deaths in any of the CR patients. The albumin-bilirubin score did not deteriorate after locoregional therapy or resection. Of seven PET-positive patients who achieved CR with atezolizumab plus bevacizumab followed by curative conversion, five achieved drug-free status. Conclusion: The achievement of CR rate by curative conversion in patients treated with atezolizumab plus bevacizumab as the preceding therapy for unresectable and TACE-unsuitable intermediate-stage HCC was 35%. Overall, 23% of patients achieved drug-free status and no recurrence was observed from this patient subgroup with CR and drug-free status. Thus, achieving CR and/or drug-free status should be a therapeutic goal for patients with intermediate-stage HCC without vascular invasion or extrahepatic spread.

Comparison of Overall Survival between Transarterial Chemoembolization and Best Supportive Care in Intermediate- Stage Hepatocellular Carcinoma.

The Thailand management guideline allows the use of transarterial chemoembolization (TACE) for the treatment of intermediate-stage hepatocellular carcinoma (HCC) in patients with decompensated cirrhosis, whereas other guidelines do not. The aim of this study was to compare the overall survival between TACE and the best supportive care (BSC) in HCC patients with Child-Pugh score 5-8 cirrhosis and in subgroups with compensated cirrhosis (Child-Pugh score 5-6) and early decompensated cirrhosis (Child-Pugh score 7-8). This retrospective study comprised 118 patients with intermediate-stage HCC. The overall survival was compared between TACE and BSC using the Kaplan-Meier method. The median overall survival time for all patients was 21.4 months in the TACE group and 8.2 months in the BSC group (P <0.001). In the subgroup analyses, the overall survival times for TACE and BSC were 26 months and 9 months, respectively, for compensated cirrhosis (P <0.001), and 14.5 months and 6.9 months, respectively, for early decompensated cirrhosis (P <0.001). In the Cox proportional-hazards model, TACE was an independent prognostic factor for prolonged overall survival in all patients [hazard ratio (HR) 0.29; 95% confidence interval (CI), 0.17-0.49; P <0.001], patients with compensated cirrhosis (HR, 0.31; 95% CI, 0.16-0.62; P <0.001), and patients with early decompensated cirrhosis (HR, 0.16; 95% CI, 0.061-0.44; P <0.001). TACE improves the overall survival in patients with intermediate-stage HCC and compensated or early decompensated cirrhosis.

Transarterial chemoembolization failure/refractoriness: A scientific concept or pseudo-proposition.

Multi-session transarterial chemoembolization (TACE) is usually needed for the treatment of intermediate-stage hepatocellular carcinoma (HCC), but it may not always have a positive influence on prognosis due to high heterogeneity of HCC. To avoid ineffective repeated TACE, the concept of TACE failure/refractoriness has been proposed by several organizations and is being addressed using tyrosine kinase inhibitors. The concept of TACE failure/refractoriness is controversial due to ambiguous definitions and low evidence-based data. To date, only a few studies have examined the rationality concerning the definition of TACE failure/refractoriness, although the concept has been introduced and applied in many TACE-related clinical trials. This review focuses on some of the issues related to different versions of TACE failure/refractoriness, the rationality of related definitions, and the feasibility of continuing TACE after so-called failure/refractoriness based on published evidence. A suggestion to re-define TAEC failure/refractoriness is also put forward.

Treatment for Intermediate-Stage Hepatocellular Carcinoma: Current Practice and Outcome in Real World Study

Background: Intermediate-stage hepatocellular carcinoma (HCC) is a very heterogeneous disease. The first line treatment for this group is transarterial chemoembolization (TACE), however, in clinical practice, not all patients are suitable for TACE. We aim to evaluate current treatment practice and outcome of patients with intermediate-stage HCC.Methods: HCC patients database from 2013 to 2016 in Cipto Mangunkusumo Hospital and Dharmais Cancer Hospital were retrospectively analyzed. Patients with intermediate-stage HCC were included in this study.Results: A total of 456 patients were diagnosed with HCC, but only 151 (33.1%) patients with intermediate-stage HCC were included. Men outnumbered women in a ratio of 3:1. The most common etiology for HCC was hepatitis B virus (HBV) infection, which accounted for 55% of patients. Fifty-two patients (34.4%) were treated with TACE as first-line treatment. Sixty-seven patients (44%) were given best supportive care due to ineligibility for TACE. Frequency of TACE varied from one to eleven times. Overall median survival was 617 days (1.7 years). One-year survival for patients undergoing TACE and liver resection was 47% and 60%, respectively. We did not compare the survival between any treatment groups because the number of patient in each group is not sufficient to be statistically analyzed.Conclusion: Only 34.4% of patients with intermediate-stage HCC was treated with TACE as first-line treatment. An improvement in the treatment strategy should be done for HCC patients in Indonesia.

Recent Trends and In-Hospital Mortality of Transarterial Chemoembolization (TACE) in Germany: A Systematic Analysis of Hospital Discharge Data between 2010 and 2019.

Simple SummaryThe minimally invasive procedure of transarterial chemoembolization (TACE) represents a standard oncologic procedure for the treatment of intermediate-stage hepatocellular carcinoma, cholangiocarcinoma, and liver metastases. Up to now, comprehensive data on recent trends and post-interventional in-hospital mortality have been largely lacking. Therefore, the aim of our study was to provide a systematic overview of the different indications and embolization techniques, as well as to identify factors associated with increased in-hospital mortality. For this purpose, we retrospectively examined 49,595 individual cases in Germany, based on standardized hospital discharge data from the German Federal Statistical Office, over the period 2010 to 2019. As a result of our study, we were able to show a correlation of in-hospital mortality with the presence of various complications, the type of embolization used, and the annual case volume. Consequently, our study may help to reduce the mortality of this therapeutic procedure in the future.(1) Background: Transarterial chemoembolization (TACE) is a minimally invasive procedure, characterized by the selective occlusion of tumor-feeding hepatic arteries, via injection of an embolizing agent and an anticancer drug. It represents a standard of care for intermediate-stage hepatocellular carcinoma (HCC), and it is also increasingly performed in cholangiocarcinoma (CCA), as well as in liver metastases. Apart from the original method, based on intra-arterial infusion of a liquid drug followed by embolization, newer particle-based TACE procedures have been introduced recently. As yet, comprehensive data on current trends of TACE, as well as its in-hospital mortality in Germany, which could help to further improve outcome following TACE, are missing. (2) Methods: Based on standardized hospital discharge data, provided by the German Federal Statistical Office from 2010 to 2019, we aimed at systematically evaluating current clinical developments and in-hospital mortality related to TACE in Germany. (3) Results: A total of 49,595 individual cases undergoing TACE were identified within the observation period. The overall in-hospital mortality was 1.00% and significantly higher in females compared to males (1.12 vs. 0.93%; p < 0.001). We identified several post-interventional complications, such as liver failure (51.49%), sepsis (33.87%), renal failure (23.9%), and liver abscess (15.87%), which were associated with a significantly increased in-hospital mortality. Moreover, in-hospital mortality significantly differed between the underlying indications for TACE (HCC: 0.83%, liver metastases: 1.22%, and CCA: 1.40%), as well as between different embolization agents (liquid embolization: 0.80%, loaded microspheres: 0.92%, spherical particles: 1.54%, and non-spherical particles: 2.84%), for which we observed large geographic differences in their frequency of use. Finally, in-hospital mortality was significantly increased in centers with a low annual TACE case volume (<15 TACE/year: 2.08% vs. >275 TACE/year: 0.45%). (4) Conclusion: Our data provide a systematic overview of indications and embolization methods for TACE in Germany. We identified a variety of factors, such as post-interventional complications, the embolization method used, and the hospitals’ annual case volume, which are associated with an increased in-hospital mortality following TACE. These data might help to further reduce the mortality of this routinely performed local-ablative procedure in the future.

Transarterial Chemoembolization Combined With Tyrosine Kinase Inhibitors for Intermediate-Stage Hepatocellular Carcinoma, What Else Can We Do?

Transarterial chemoembolization (TACE) has been considered the standard treatment for intermediate-stage hepatocellular carcinoma (HCC). However, intermediate‐stage HCC is highly heterogeneous with a broad population with varying tumour burdens, liver function. This suggests that TACE monotherapy treatment might not be suitable for all patients with intermediate‐stage HCC. The administration of tyrosine kinase inhibitors (TKIs) has become an important treatment option for improving the prognosis of patients with advanced HCC. Over the years, several trials have been conducted to explore the effects of TACE combined with TKIs for intermediate-stage HCC. However, the clinical efficacy is still controversial, and its potential clinical utility needs to be confirmed. This review will focus on the recent progress of TACE combined TKIs for intermediate-stage HCC.