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

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

Locoregional therapies for hepatocellular carcinoma: The current status and future perspectives.

Hepatocellular carcinoma (HCC) is one of the most common cancers and a leading cause of cancer-related mortality. Locoregional therapies (LRTs) play a crucial role in HCC management and are selectively adopted in real-world practice across various stages. Choosing the best form of LRTs depends on technical aspects, patient clinical status and tumour characteristics. Previous studies have consistently highlighted the efficacy of combining LRTs with molecular targeted agents in HCC treatment. Recent studies propose that integrating LRTs with immune checkpoint inhibitors and molecular targeted agents could provide substantial therapeutic benefits, a notion underpinned by both basic and clinical evidence. This review summarised the current landscape of LRTs in HCC and discussed the anticipated outcomes of combinations with immunotherapy regimens.

Transarterial Chemoembolization with Epirubicin-Loaded Microspheres for Hepatocellular Carcinoma: A Prospective, Single-Arm, Multicenter, Phase 2 Study (STOPPER Trial).

PURPOSE: While the role of drug-eluting beads transarterial chemoembolization (DEB-TACE) for hepatocellular carcinoma (HCC) is established, questions regarding appropriate bead size for use in patients remain. This trial evaluated the effectiveness and safety of DEB-TACE using small-size (≤ 100 µm) microspheres loaded with epirubicin. MATERIALS AND METHODS: This prospective, single-arm, multicenter study enrolled patients diagnosed with HCC who underwent DEB-TACE using 40 (range, 30-50), 75 (range, 60-90), or 100 (range, 75-125) µm epirubicin-loaded microspheres (TANDEM microspheres, Varian Medical). Bead size was at the discretion of treating physicians and based on tumor size and/or vascular structure. The primary outcome measure was 6-month objective response rate (ORR). Secondary outcome measures were 30-day and 3-month ORR, time to tumor progression and extrahepatic spread, proportion of progression-free survival and overall survival (OS) at one year, and incidence of treatment-associated adverse events. RESULTS: Data from 108 patients from ten centers was analyzed. Six-month ORR was 73.3 and 71.3% based on European association for the study of the liver (EASL) and modified response evaluation criteria in solid tumors (mRECIST) criteria, respectively. Thirty-day ORR was 79.6% for both EASL and mRECIST criteria with 3-month ORR being 80.0 and 81.0%, respectively, for each criteria. One-year PPF and OS rate were 60.3 and 94.3%. There was a total of 30 SAEs reported to be likely to definitely associated with microsphere (n = 9), epirubicin (n = 9), or procedure (n = 12) with none resulting in death. CONCLUSION: DEB-TACE using epirubicin-loaded small-sized (≤ 100 µm) microspheres demonstrates promising local tumor control and acceptable safety in patients with HCC. TRIAL REGISTRATION: Clinicaltrials.gov NCT03113955; registered April 14, 2017. Trial Registration Clinicaltrials.gov NCT03113955; registered April 14, 2017. LEVEL OF EVIDENCE: 2, Prospective, Non-randomized, Single-arm, study.

Emergent TIPS for acute gastroesophageal variceal bleeding in cirrhotic patients with hepatocellular carcinoma.

OBJECTIVES: To estimate the safety and effectiveness of emergent transjugular intrahepatic portosystemic shunt (TIPS) creation for acute variceal bleeding (AVB) in cirrhotic patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Data of thirty-three patients with AVB and HCC undergoing emergent TIPS creation from January 2016 to January 2022 were enrolled and were retrospectively analyzed. The primary outcomes were the safety of emergent TIPS creation, the bleeding control rate, and the rebleeding rate. The secondary outcomes included overall survival (OS), liver function, overt hepatic encephalopathy (HE), and shunt dysfunction. RESULTS: Emergent TIPS creation was technically successful in 33 patients (100%) and one (3.0%) patient suffered a major procedure-related adverse event. The control rate of bleeding (within 5 days) was 100%. During a median follow-up period of 26.3 months, rebleeding occurred in 6 (18.2%) patients. The median OS was 20.0 months. The 6-week and 1-year survival rates were 87% and 65%, respectively. Laboratory tests showed no significant impairment of liver function following TIPS creation. The incidences of overt HE and shunt dysfunction were 24.2% and 6.1%, respectively. CONCLUSION: Emergent TIPS creation is feasible and effective for treatment of AVB in cirrhotic patients with HCC.

Prognosis Prediction of CRAFITY Score in HCC Undergoing TACE Combined with PD-(L)1 Inhibitors and Molecular Targeted Therapy.

Background: The CRAFITY (C-reactive protein and alpha-fetoprotein in immunotherapy) score has demonstrated prognostic significance in hepatocellular carcinoma (HCC) patients undergoing immunotherapy. The study aimed to validate accuracy of CRAFITY score on predicting prognosis for patients with HCC treated with transarterial chemoembolization (TACE) combined with PD-(L)1 inhibitors and molecular targeted therapy. Methods: Eighty-five HCC patients who underwent TACE in combination with molecular targeted therapy (MTT) and PD-(L)1 Inhibitors were consecutively enrolled from November 2019 to November 2022. Patients were divided into CRAFITY 0 score (n=32), CRAFITY 1 score (n=31), and CRAFITY 2 score (n=22), respectively. The primary outcomes were overall survival (OS) and progression-free survival (PFS), and the secondary outcomes included tumor response rate and treatment-related adverse events (TRAEs). Factors affecting survival were identified via Cox regression analysis. Results: The median overall survival (OS) for HCC patients with CRAFITY scores of 0, 1, and 2 was 33.4 months (95% confidence interval [CI]: 27.1-39.7), 34.5 months (95% CI: 23.1-45.9), and 24.2 months (95% CI: 13.9-39.3), respectively, there were statistical differences among the three groups (p<0.05). The progression-free survival (PFS) was 14.1 months (95% CI: 10.0-18.2), 14.1 months (95% CI: 9.0-19.2), and 9.3 months (95% CI: 7.2-11.4) for patients with CRAFITY scores of 1, 2, and 3, respectively, with a significant difference between the three groups (p<0.05). In patients with CRAFITY scores of 1, 2, and 3, the disease control rates (DCR) were 94%, 84%, and 73%, respectively (p < 0.05), while the overall response rates (ORR) were 78.1%, 67.7%, and 59.1%, respectively (p = 0.318). A higher CRAFITY score showed a correlation with an increased frequency of fatigue and grade 3 fever (p<0.05). Moreover, CRAFITY 2 score was an independent risk factor for both OS (HR = 2.610(1.281-4.564), p = 0.014) and PFS (HR = 2.419(1.281-4.564), p = 0.006). Conclusion: The CRAFITY score may provide an efficient predictive capacity for prognosis in HCC patients undergoing TACE combined with PD-(L)1 inhibitors and molecular targeted therapy.

Transarterial Chemoembolization for Patients with Unresectable Hepatocellular Carcinoma with Child-Pugh B7.

Background and Objectives: This study aimed to evaluate the efficacy and safety of transarterial chemoembolization (TACE) in patients with unresectable early or intermediate hepatocellular carcinoma (HCC) and Child-Pugh (CP)-B liver dysfunction. Methods: This multicenter retrospective study enrolled patients with treatment-naïve HCC treated with TACE monotherapy between January 2012 and December 2020 at six Chinese hospitals. The primary outcome was overall survival (OS), and the secondary outcomes included the objective response rate (ORR) according to the modified RECIST and adverse events (AEs). Propensity score matching (PSM) was performed to reduce bias between the CP-B and CP-A groups. Results: A total of 847 patients were included in the study. CP-A patients had significantly longer OS (median, 22.0 vs 19.3 months, P = 0.032) than CP-B (score of 7-9) patients, but a non-significant trend compared with CP-B (score of 7) patients (median, 22.0 vs 20.5 months, P = 0.254). After PSM, the median OS was 22.7 months for CP-A patients, while it was 19.3 months for CP-B (score of 7-9) patients (p = 0.026) and 20.5 months for CP-B (score of 7) patients (p = 0.155). CP-A patients achieved a significantly better ORR (53.0% vs 35.8%, P < 0.05) compared to CP-B (score of 7-9) patients, but a non-significant trend was observed in CP-B (score of 7) patients (53.0% vs 51.1%, P > 0.05). The post-embolization syndrome rates in the CP-A and CP-B (score of 7) cohorts were 52.1% and 53.3%, respectively. No new safety concerns were observed. Conclusion: Patients with HCC with a CP score of 7 receiving TACE showed a similar prognosis and safety profile to CP-A patients.

Prognostic Performance of the China Liver Cancer Staging System in Hepatocellular Carcinoma Following Transarterial Chemoembolization.

Background and Aims: To validate prognostic performance of the China liver cancer (CNLC) staging system as well as to compare these parameters with those of the Barcelona Clinic Liver Cancer (BCLC) staging system for Chinese hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE). Methods: This multicenter retrospective study included 1,124 patients with HCC between January 2012 and December 2020 from six Chinese hospitals. Based on overall survival (OS), the prognostic performance outcomes for the CNLC and BCLC staging systems were compared by model discrimination [C statistic and Akaike information criterion (AIC)], monotonicity of the gradient (linear trend chi-square test), homogeneity (likelihood ratio chi-square test), and calibration (calibration plots). A prospective cohort of 44 patients receiving TACE-based therapy included between January 2021 and December 2022 was used to prospectively validate the outcomes. Results: Median OS was 19.1 (18.2-20.0) months, with significant differences in OS between stages defined by the CNLC and BCLC observed (p<0.001). The CNLC performed better than the BCLC regarding model discrimination (C-index: 0.661 vs. 0.644; AIC: 10,583.28 vs. 10,583.72), model monotonicity of the gradient (linear trend chi-square test: 66.107 vs. 57.418; p<0.001), model homogeneity (159.2 vs. 158.7; p<0.001). Both staging systems had good model calibration. Similar results were observed in the prospective cohort. Conclusions: Combining model discrimination, gradient monotonicity, homogeneity, and calibration, the CNLC performed better than the BCLC for Chinese HCC patients receiving TACE.

Real-world efficacy and safety of TACE plus camrelizumab and apatinib in patients with HCC (CHANCE2211): a propensity score matching study.

OBJECTIVES: This study aimed to investigate the efficacy and safety of transarterial chemoembolization (TACE) plus camrelizumab, a monoclonal antibody targeting programmed death-1, and apatinib for patients with intermediate and advanced hepatocellular carcinoma (HCC) in a real-world setting. METHODS: A total of 586 HCC patients treated with either TACE plus camrelizumab and apatinib (combination group, n = 107) or TACE monotherapy (monotherapy group, n = 479) were included retrospectively. Propensity score matching analysis was used to match patients. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and safety in the combination group were described in comparison to monotherapy. RESULTS: After propensity score matching (1:2), 84 patients in the combination group were matched to 147 patients in the monotherapy group. The median age was 57 years and 71/84 (84.5%) patients were male in the combination group, while the median age was 57 years with 127/147 (86.4%) male in the monotherapy group. The median OS, PFS, and ORR in the combination group were significantly higher than those in the monotherapy group (median OS, 24.1 vs. 15.7 months, p = 0.008; median PFS, 13.5 vs. 7.7 months, p = 0.003; ORR, 59.5% [50/84] vs. 37.4% [55/147], p = 0.002). On multivariable Cox regression, combination therapy was associated with significantly better OS (adjusted hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.26-0.64; p < 0.001) and PFS (adjusted HR, 0.52; 95% CI, 0.37-0.74; p < 0.001). Grade 3 or 4 adverse events occurred in 14/84 (16.7%) and 12/147 (8.2%) in the combination and monotherapy groups, respectively. CONCLUSIONS: TACE plus camrelizumab and apatinib showed significantly better OS, PFS, and ORR versus TACE monotherapy for predominantly advanced HCC. CLINICAL RELEVANCE STATEMENT: Compared with TACE monotherapy, TACE plus immunotherapy and molecular targeted therapy showed better clinical efficacy for predominantly advanced HCC patients, with a higher incidence of adverse events. KEY POINTS: • This propensity score-matched study demonstrates that TACE plus immunotherapy and molecular targeted therapy have a longer OS, PFS, and ORR compared with TACE monotherapy in HCC. • Grade 3 or 4 adverse events occurred in 14/84 (16.7%) patients treated with TACE plus immunotherapy and molecular targeted therapy compared with 12/147 (8.2%) patients in the monotherapy group, while no grade 5 adverse events were observed in all cohorts.

Feasibility of computed tomography portal venography in the preoperative evaluation of emergent TIPS creation for cirrhotic patients with acute variceal bleeding.

OBJECTIVES: To evaluate the feasibility of computed tomography portal venography (CTPV) in the preoperative evaluation of emergent transjugular intrahepatic portosystemic shunt (TIPS) creation for cirrhotic patients with acute variceal bleeding (AVB). METHODS: One hundred and forty-eightcirrhotic patients with AVB undergoing emergent TIPS creation from January 2016 to December 2022 in our institution were enrolled in the retrospective study. The primary outcome was the consistency between CTPV and endoscopy in the classification and grading of gastroesophageal varices (GEVs). The second outcome was extraluminal CTPV findings. The consistency of CTPV and endoscopy in the classification and grading of GEVs was determined by Kappa values. RESULTS: Emergent TIPS creation was technically successful in all patients. Forty-five patients underwent preoperative endoscopy. The results of CTPV diagnosis of GEVs classification were that 112, 28, and 8 patients were classified as gastroesophageal varices type 1 (GOV1), GOV2, and isolated gastric varices type 1 (IGV1), respectively. In diagnosing the classification and grading of GEVs, CTPV showed substantial agreement with preoperative endoscopy, with Kappa values of 0.823 and 0.625, respectively. CTPV provided the afferent and afferent vessels of GEVs for emergent TIPS creation. CONCLUSION: CTPV is feasible and effective to act as an alternative preoperative evaluation method to endoscopy for cirrhotic patients with AVB undergoing emergent TIPS creation.

Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma (CHANCE001).

There is considerable potential for integrating transarterial chemoembolization (TACE), programmed death-(ligand)1 (PD-[L]1) inhibitors, and molecular targeted treatments (MTT) in hepatocellular carcinoma (HCC). It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations. In this nationwide, retrospective, cohort study, 826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT (combination group, n = 376) or TACE monotherapy (monotherapy group, n = 450) were included from January 2018 to May 2021. The primary endpoint was progression-free survival (PFS) according to modified RECIST. The secondary outcomes included overall survival (OS), objective response rate (ORR), and safety. We performed propensity score matching approaches to reduce bias between two groups. After matching, 228 pairs were included with a predominantly advanced disease population. Median PFS in combination group was 9.5 months (95% confidence interval [CI], 8.4-11.0) versus 8.0 months (95% CI, 6.6-9.5) (adjusted hazard ratio [HR], 0.70, P = 0.002). OS and ORR were also significantly higher in combination group (median OS, 19.2 [16.1-27.3] vs. 15.7 months [13.0-20.2]; adjusted HR, 0.63, P = 0.001; ORR, 60.1% vs. 32.0%; P < 0.001). Grade 3/4 adverse events were observed at a rate of 15.8% and 7.5% in combination and monotherapy groups, respectively. Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS, OS, and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice, with an acceptable safety profile.

Role of Transarterial Chemoembolization in the Treatment of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. According to the Barcelona Clinic Liver Cancer (BCLC) staging system, transarterial chemoembolization (TACE) is the first-line recommendation for intermediate-stage HCC. In real-world clinical practice, TACE also plays an important role in early- and advanced-stage HCC. This review article by the experts from Chinese Liver Cancer Clinical Study Alliance (CHANCE) summarizes the available clinical evidence pertaining to the current application of TACE in patients with early-, intermediate-, and advanced-stage HCC. In addition, combination of TACE with other treatment modalities, especially immunotherapy, is reviewed.

Emergent Transjugular Intrahepatic Portosystemic Shunt as a First-Line Therapy in Patients with Cirrhosis with Acute Gastroesophageal Variceal Hemorrhage.

PURPOSE: To investigate the safety and effectiveness of emergent transjugular intrahepatic portosystemic shunt (TIPS) as first-line therapy in patients with advanced cirrhosis with acute variceal hemorrhage. MATERIALS AND METHODS: From July 2016 to June 2019, 76 patients with advanced cirrhosis and acute variceal hemorrhage were included in this retrospective study. All patients underwent emergent TIPS as first-line therapy within 24 hours. Gastroesophageal varices in patients with cirrhosis were diagnosed with contrast-enhanced computed tomography because emergent endoscopy has not been routinely performed in this center. The primary outcomes were the control rate of bleeding and the rate of rebleeding. Secondary outcomes were the technical success rate of procedure, transplantation-free survival, the mean hospitalization time, the time of stay in the intensive care unit, and adverse events. RESULTS: All patients underwent TIPS creation successfully and were transferred to general wards. The median follow-up time was 21.7 months (interquartile range, 12.6-28.1 months). The control rate of bleeding (≤5 days) was 100%. The rates of early (>5 days to 6 weeks) and late (>6 weeks to 2 years) rebleeding were 6.6% and 1.3%, respectively. The 6-week, 1-year, and 2-year transplantation-free survival rates were 94.7%, 93.4%, and 84.6%, respectively. The incidences of acute liver failure, hepatic encephalopathy, and shunt dysfunction were 5.3%, 25%, and 5.3%, respectively. CONCLUSIONS: Emergent TIPS as a first-line therapy in patients with advanced cirrhosis with acute variceal hemorrhage is safe and effective. This study provides an alternative approach for medical centers without emergent endoscopy facility to manage the condition.

Transarterial Chemoembolization Combined with Immune Checkpoint Inhibitors Plus Tyrosine Kinase Inhibitors versus Immune Checkpoint Inhibitors Plus Tyrosine Kinase Inhibitors for Advanced Hepatocellular Carcinoma.

Objective: This study aimed to evaluate the effectiveness and safety of transarterial chemoembolization (TACE) in combination with immune checkpoint inhibitors (ICIs) plus tyrosine kinase inhibitors (TKIs) (TACE+IT) versus ICIs plus TKIs (IT) for advanced hepatocellular carcinoma (HCC). Materials and Methods: Data of consecutive advanced HCC patients receiving TACE+IT or IT between January 2019 and December 2021 were included and were retrospectively analyzed. Propensity score matching (PSM) was performed to reduce bias due to confounding variables. The primary outcome of the study was overall survival (OS). The secondary outcomes were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs), respectively. Results: Sixty-four patients were enrolled in the study, among which 24 and 40 received TACE+IT and IT, respectively. The PSM cohort included 24 patients receiving TACE+IT (TACE+IT group) and 24 patients receiving IT (IT group) alone. During a median follow-up of 23 months, patients in TACE+IT group had significantly longer OS (median, 17.3 vs 11.8 months, P = 0.023), better ORR (41.7% vs 12.5%, P = 0.023) and DCR (79.2% vs 50.0%, P = 0.035) than those in the IT group, whereas a non-significant trend in PFS (median, 7.4 vs 6.7 months, P = 0.23) was observed. According to multivariable cox regression analysis, it was found that treatment modality was the only independent risk factor for OS (HR = 0.404, 95% CI = 0.179-0.911, P < 0.05). There were no remarkable differences in AEs associated with ICIs and TKIs between the two groups, with the exception of gastrointestinal reaction. Conclusion: TACE combined with ICIs plus TKIs significantly improved OS, ORR, and DCR and showed a relatively longer PFS trend over ICIs combined with TKIs for advanced HCC.

Recent Update on Immunotherapy and Its Combination With Interventional Therapies for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common and deadly malignancies worldwide. Approximately, 80% of patients are initially diagnosed at intermediate or advanced stages, which means that curative therapies are unable to be performed. In most cases, systemic treatment is ineffective, especially when conventional cytotoxic agents are used. Sorafenib has been the only systemic agent proven to be effective in treating advanced HCC for over a decade. The rapid development of immunotherapy has remarkably revolutionized the management of advanced HCC. Besides, the combination of immunotherapy with molecular targeted agents or locoregional treatments is emerging as an effective tool for enhancing immunity. In the review, an overview of immunotherapy and its combination therapies for HCC is presented.

Subsequent Treatment after Transarterial Chemoembolization Failure/Refractoriness: A Review Based on Published Evidence.

Transarterial chemoembolization (TACE) is widely applied for the treatment of hepatocellular carcinoma. Repeat TACE is often required in clinical practice because a satisfactory tumor response may not be achieved with a single session. However, repeated TACE procedures can impair liver function and increase treatment-related adverse events, all of which prompted the introduction of the concept of "TACE failure/refractoriness". Mainly based on evidence from two retrospective studies conducted in Japan, sorafenib is recommended as the first choice for subsequent treatment after TACE failure/refractoriness. Several studies have investigated the outcomes of other subsequent treatments, including locoregional, other molecular targeted, anti-programmed death-1/anti-programed death ligand-1 therapies, and combination therapies after TACE failure/refractoriness. In this review, we summarize the up-to-date information about the outcomes of several subsequent treatment modalities after TACE failure/refractoriness.

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.

Transarterial Chemoembolization Combined With Immune Checkpoint Inhibitors and Tyrosine Kinase Inhibitors for Unresectable Hepatocellular Carcinoma: Efficacy and Systemic Immune Response.

Background: Locoregional therapy combined with systemic therapy can further improve the prognoses for HCC. However, the efficacy of TACE combined with ICIs and TKIs for HCC and whether this triple therapy can activate systemic immune response are still unknown. Purpose: To identify the efficacy of TACE+ICIs+TKIs for unresectable hepatocellular carcinoma (uHCC) and its effect on systemic immunity. Materials and Methods: This single-center retrospective study was approved by the Institutional Review Board. From August 1, 2019, to March 30, 2021, patients with uHCC who received the combination therapy of TACE+ICIs+TKIs were included. Peripheral blood samples were collected at baseline and once a month for 4 months after treatment. Lymphocyte subsets were measured by flow cytometry. Immunoglobulins were measured using the immune turbidimetric method. The dynamic change trend of circulating parameters was tested using simple linear regression. Results: Fifty-three patients with a mean age of 59 ± 10.6 years were included. TTP was 8.0 months (95% CI, 5.5-10.5) and PFS was 8.5 months (95% CI, 5.4-11.5). ORR was 52.8% and DCR was 81.1%. Twenty patients had completed analysis of biomarkers in peripheral blood. For cellular immune response, the level of circulating CD8+, CD3+ T cells and NK cells increased, the frequency of CD4+T cells and the CD4+/CD8+ ratio decreased, and among them, CD8+ T cells increased significantly. For humoral immune response, there was a significant decrease in B cells and a significant increase in Ig G, Ig κ, and Ig λ. Moreover, Ig G, Ig κ, and Ig λ were related to tumor response. Conclusion: TACE+ICIs+TKIs showed considerable efficacy in patients with uHCC. This triple therapy activated not only cell immune but also humoral immune activation. Circulating Ig G, Ig λ, and Ig κ can serve as potential biomarkers.

Efficacy and Safety of Radioactive 125I Seed Implantation for Patients with Oligo-Recurrence Soft Tissue Sarcomas.

PURPOSE: To evaluate the efficacy and safety of computed tomography-guided radioactive iodine-125 (125I) seed implantation for oligo-recurrence soft tissue sarcomas following surgical resection. MATERIALS AND METHODS: Patients with oligo-recurrence soft tissue sarcomas after curative surgical resection between June 2013 and December 2020 were included. The primary outcome measure was objective response rate according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). The secondary outcomes included progression-free survival, overall survival, and safety profiles. RESULTS: Twenty-nine patients receiving computed tomography-guided 125I seed implantation were included in the study. The objective response rates at 2-, 6- and 12-month follow-up were 48.3%, 65.5% and 40.9%, respectively. The median progression-free survival was 11.3 months. The median overall survival was 25.1 months, with a 1- and 2-year overall survival rate of 81.5% and 50.0%, respectively. No severe treatment-related adverse effects occured. CONCLUSION: 125I seed implantation has the potential to be an effective and safe treatment for oligo-recurrence soft tissue sarcomas after surgical resection.

Large Paraumbilical Vein Shunts Increase the Risk of Overt Hepatic Encephalopathy after Transjugular Intrahepatic Portosystemic Shunt Placement.

Background: This study aimed to evaluate whether a large paraumbilical vein (L-PUV) was independently associated with the occurrence of overt hepatic encephalopathy (OHE) after the implantation of a transjugular intrahepatic portosystemic shunt (TIPS). Methods: This bi-center retrospective study included patients with cirrhotic variceal bleeding treated with a TIPS between December 2015 and June 2021. An L-PUV was defined in line with the following criteria: cross-sectional areas > 83 square millimeters, diameter ≥ 8 mm, or greater than half of the diameter of the main portal vein. The primary outcome was the 2-year OHE rate, and secondary outcomes included the 2-year mortality, all-cause rebleeding rate, and shunt dysfunction rate. Results: After 1:2 propensity score matching, a total of 27 patients with an L-PUV and 54 patients without any SPSS (control group) were included. Patients with an L-PUV had significantly higher 2-year OHE rates compared with the control group (51.9% vs. 25.9%, HR = 2.301, 95%CI 1.094−4.839, p = 0.028) and similar rates of 2-year mortality (14.8% vs. 11.1%, HR = 1.497, 95%CI 0.422−5.314, p = 0.532), as well as variceal rebleeding (11.1% vs. 13.0%, HR = 0.860, 95%CI 0.222−3.327, p = 0.827). Liver function parameters were similar in both groups during the follow-up, with a tendency toward higher shunt patency in the L-PUV group (p = 0.067). Multivariate analysis indicated that having an L-PUV (HR = 2.127, 95%CI 1.050−4.682, p = 0.037) was the only independent risk factor for the incidence of 2-year OHE. Conclusions: Having an L-PUV was associated with an increased risk of OHE after a TIPS. Prophylaxis management should be considered during clinical management.

Clinical practice of transarterial chemoembolization for hepatocellular carcinoma: consensus statement from an international expert panel of International Society of Multidisciplinary Interventional Oncology (ISMIO).

IMPORTANCE: Transarterial chemoembolization (TACE) has been associated with a wide range of practice variations for hepatocellular carcinoma (HCC) between the East and the West. This considerable ambiguity may lead to the heterogeneous quality in treatment and have a negative impact on the role of TACE in the overall multidisciplinary HCC treatment system. OBJECTIVE: It may be a good start to establish a guideline worldwide to have this consensus from experts who represent east and west, although it does not cover all aspects of TACE. EVIDENCE REVIEW: An international expert panel on TACE is convened to cluster the expert's opinions and summary a standard consensus. This panel committee consist of leading physicians in TACE on HCC from USA, France, Japan, Singapore, Korea, China, and so on. The first-round face-to-face consensus meeting was held during in Nanjing, China in October 2019. The second-round conference for revision of the consensus was held during the Annual Meeting of Chinese College of Interventionalists in August 2020 by a hybrid format of a Webinar and roundtable meeting. After several on-line revisions, the final manuscript was approved by all members of the panel in June 2021. FINDINGS: The consensus statements were organized into the following categories: patients' selection, performing the procedure, TACE outcomes, repeat TACE, TACE failure/refractory, and TACE-based combination treatments. CONCLUSIONS AND RELEVANCE FOR REVIEWS: More and more evidences have showed the better outcomes with strategy of combined TACE with other local therapies such as ablations. The most-recently developing strategy of combined TACE with PD-1/PD-L1 plus tyrosine kinase inhibitor (TKI) agents has shined a light to the HCC patients, especially to those with high risk of tumor recurrence after treatment or TACE failure/refractory.