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.

TACE with dicycloplatin in patients with unresectable hepatocellular carcinoma: a multicenter randomized phase II trial.

OBJECTIVES: To investigate the efficacy and safety of dicycloplatin as chemotherapeutic regimen in transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). METHODS: In this randomized, open-label, phase II trial, patients with unresectable HCC who were TACE treatment-naïve or experienced recurrence after surgical resection or ablation were enrolled at 7 centers in China from March 2019 to November 2019. Participants were randomly assigned (1:1:1) to receive TACE with chemotherapeutic regimen of dicycloplatin alone (group A1), dicycloplatin plus epirubicin (group A2), or epirubicin alone (group B). The primary endpoint was objective response rate (ORR). The secondary endpoints included disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), and safety. RESULTS: The ORR at 6 months in group A1 (n = 22) was significantly better than that in group B (p = 0.093; 90% confidence interval [CI], 1.03-9.45). The DCR in group A1 was significantly higher than that in group B (p = 0.045; 90% CI, 1.29-12.88). There was no significant difference in DOR among the groups (p = 0.271). The median PFS were 6.00 and 3.05 months in groups A2 (n = 25) and B (n = 24), respectively (p = 0.061). Grade 3 or worse adverse events were similar among groups in the safety population (p = 0.173). CONCLUSION: TACE with dicycloplatin was comparably safe and well tolerable as epirubicin alone in patients with unresectable HCC. Compared with epirubicin alone, significant improvement in ORR and DCR when dicycloplatin was applied, as well as prolonged PFS when dicycloplatin plus epirubicin was applied, was generated. KEY POINTS: • To our knowledge, this is the first multicenter randomized trial to assess the efficacy and safety of TACE with dicycloplatin in patients with unresectable HCC. • This phase II trial showed that TACE with dicycloplatin alone or plus epirubicin was comparably safe and well tolerable as epirubicin alone. • Significant improvements in ORR, DCR when dicycloplatin was applied, and prolonged PFS when dicycloplatin plus epirubicin was applied were recorded compared with epirubicin alone.

Benchmark Status of Women Interventional Radiologists in China.

PURPOSE: To evaluate the current status of women interventional radiologists in China and discuss possible measures to boost their representation in this male-dominated field for a more diverse workplace environment in the future. MATERIALS AND METHODS: The list of Chinese interventional radiologists obtained from the Chinese College of Interventionalists was retrospectively reviewed. Key information was extracted from the database, including sex, chronologic trends of representation of women interventional radiologists, position, education level, geographic distribution, interventional radiology (IR) practice time, departmental affiliation, and hospital classification. RESULTS: Of the 13,855 entries, 7,324 (52.9%) were interventional radiologists having valid information. Among them, 684 (9.3%) were identified as women. The number of women interventional radiologists has continued to increase since the first woman registered in 1992. The average age of women interventional radiologists was 39.1 years ± 5.7 (range, 26-50). The majority of them were attending physicians (n = 280; 40.9%) with a bachelor's degree (n = 363; 53.1%). Most women interventional radiologists (n = 215, 31.4%) joined this specialty 5-9 years after becoming physicians, whereas 128 (18.7%) started practicing IR from the very beginning. A total of 42.4% of women interventional radiologists were from the departments of IR and cardiology. CONCLUSIONS: Although the total number shows an upward trend, women interventional radiologists are still underrepresented. Education level, geographic areas, and other socioeconomic factors may simultaneously influence the population size of women interventional radiologists in China.

Venous thromboembolism in non-COVID-19 population during the pandemic: a nationwide multicenter retrospective survey.

Impact of pandemic on the incidence of venous thromboembolism (VTE) in non-COVID-19 patients is undetermined. Thus, a nationwide multicenter retrospective survey was conducted to evaluate the disease burden in non-COVID-19 population. This multi-center survey involved 94 hospitals from 24 provinces in the mainland of China, and collected data on non-COVID-19 patients admitted to the radiology departments due to VTE between January 24 and April 16, 2020. Baseline characteristics, VTE risk factors, clinical manifestations and the treatments were compared with those in the same period of 2019. 3,358 patients with VTE from 74 hospitals were included in this study (1,458 in 2020, 1,900 in 2019). Most aged ≥ 50 years (80.6% in the pandemic, 81.2% in 2019). The number of patients aged 30-39 years increased from 3.9% in 2019 period to 5.8% in the pandemic (p = 0.009). Among the VTE risk factors, the rate of decreased activity increased significantly in the pandemic, and was much higher than that in 2019 (30.7% vs 22.6%, p < 0.0001). Under the risk of decreased activity, patients with comorbidities chronic diseases, especially diabetes, showed significantly a higher incidence of VTE (30.4% vs 22.0%, p < 0.0001). In the pandemic period, fewer patients were treated with anticoagulation alone (33.5% vs 36.7%, p = 0.05), and more underwent inferior vena cava filter (IVCF) implantation, compared with those in 2019 (66.5% vs 63.2%, p = 0.046). The pandemic increased the VTE risk of decreased activity among the non-COVID-19 population. Patients with comorbidities, especially diabetes, have a significant higher risk of VTE during the pandemic.

COVID-19: What Should Interventional Radiologists Know and What Can They Do?

The outbreak of coronavirus disease 2019 (COVID-19) in late December 2019 in Wuhan, China, has been characterized as a "pandemic" by the World Health Organization and has resulted in 81,603 confirmed cases in China, among the 334,981 cases confirmed in 189 countries as of 09:00 am, March 24, 2020 (China central standard time). During the past 3 months, hundreds of thousands of Chinese health care workers, including interventional radiologists (IRs), have been fighting this battle against the horrifying COVID-19 disease. As IRs, what should we know and what can we do when facing this challenge? This paper shares the experience we have gone through.

Comparison of 125 Iodine Seed-Loaded Stents with Different Diameters in Esophageal Cancer: A Multicenter Retrospective Cohort Study.

Currently, there are no recommendations or guidelines concerning the preferred diameter of esophageal stents for palliative treatment, owing to the lack of adequate evidence. We therefore conducted a retrospective cohort study to evaluate whether 18 mm stents would achieve a similar function of dysphagia relief with fewer complications and longer survival compared to 20 mm stents. Esophageal cancer patients who underwent 125 iodine seed-loaded stent placement with a diameter of either 18 mm (n = 103) or 20 mm (n = 54) were included at five hospitals in China. The stabilized inverse probability of treatment weighting (IPTW) was used to control potential confounding factors and bias that are inherent in a retrospective study. The primary endpoint was dysphagia relief. Stent-related complications and overall survival were assessed as the secondary endpoints. In the IPTW-adjusted analysis, no significant difference was found in the dysphagia score between the two groups either at 1 week after stent placement or at the last week before death. Despite a comparable rate of overall complications, there was a significantly lower incidence of severe retrosternal pain (15.4% vs. 32.7%, p = 0.013) and a trend toward longer survival (median survival, 176 days [95% confidence interval (CI) 144 to 209] vs. 109 days [92 to 126], p = 0.057) in the 18 mm group. An irradiated stent with a diameter of 18 mm showed a similar outcome of dysphagia relief to that achieved with a 20 mm diameter stent, but halved the incidence of retrosternal pain after stent placement.

Risk Prediction for Early Biliary Infection after Percutaneous Transhepatic Biliary Stent Placement in Malignant Biliary Obstruction.

PURPOSE: To establish a nomogram for predicting the occurrence of early biliary infection (EBI) after percutaneous transhepatic biliary stent (PTBS) placement in malignant biliary obstruction (MBO). MATERIALS AND METHODS: In this multicenter study, patients treated with PTBS for MBO were allocated to a training cohort or a validation cohort. The independent risk factors for EBI selected by multivariate analyses in the training cohort were used to develop a predictive nomogram. An artificial neural network was applied to assess the importance of these factors in predicting EBI. The predictive accuracy of this nomogram was determined by concordance index (c-index) and a calibration plot, both internally and externally. RESULTS: A total of 243 patients (training cohort: n = 182; validation cohort: n = 61) were included in this study. The independent risk factors were length of obstruction (odds ratio [OR], 1.061; 95% confidence interval [CI], 1.013-1.111; P = .012), diabetes (OR, 5.070; 95% CI, 1.917-13.412; P = .001), location of obstruction (OR, 2.283; 95% CI, 1.012-5.149; P = .047), and previous surgical or endoscopic intervention (OR, 3.968; 95% CI, 1.709-9.217; P = .001), which were selected into the nomogram. The c-index values showed good predictive performance in the training and validation cohorts (0.792 and 0.802, respectively). The optimum cutoff value of risk was 0.25. CONCLUSIONS: The nomogram can facilitate the early and accurate prediction of EBI in patients with MBO who underwent PTBS. Patients with high risk (> 0.25) should be administered more effective prophylactic antibiotics and undergo closer monitoring.

Nomogram and Artificial Neural Network for Prognostic Performance on the Albumin-Bilirubin Grade for Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization.

PURPOSE: To construct the albumin-bilirubin (ALBI) grade and the Child-Turcotte-Pugh (CTP) score based on nomograms, as well as to develop an artificial neural network (ANN) to compare the prognostic performance of the 2 scores for hepatocellular carcinoma (HCC) that has undergone transarterial chemoembolization. MATERIALS AND METHODS: This multicentric retrospective study included patients with HCC who underwent transarterial chemoembolization monotherapy as an initial treatment at 4 institutions between January 2008 and December 2016. In the training cohort, significant risk factors associated with overall survival (OS) were identified by univariate and multivariate analyses. The prognostic nomograms and ANN were established and then validated in 2 validation cohorts. RESULTS: A total of 838 patients (548, 115, and 175 in the training cohort and validation cohorts 1 and 2, respectively) were included. The median OS was 10.4, 15.7, and 9.2 months in the training cohort and validation cohorts 1 and 2, respectively. In the training cohort, both ALBI grade and CTP score were identified as significant risk factors. The ALBI grade and CTP score based on nomograms were established separately and showed similar prognostic performance when assessed externally in validation cohorts (C-index in validation cohort 1: 0.823 vs 0.802, P = .417; in validation cohort 2: 0.716 vs 0.729, P = .793). ANN showed that ALBI grade had higher importance on survival prediction than CTP score. CONCLUSIONS: ALBI grade performs at least no worse than CTP score regarding survival prediction for HCC receiving transarterial chemoembolization. Considering the easy application, ALBI grade has the potential to be regarded as an alternative to CTP score.

Irradiation stents vs. conventional metal stents for unresectable malignant biliary obstruction: A multicenter trial.

BACKGROUND & AIMS: Placement of an irradiation stent has been demonstrated to offer longer patency and survival than an uncovered self-expandable metallic stent (SEMS) in patients with unresectable malignant biliary obstruction (MBO). We aim to further assess the efficacy of an irradiation stent compared to an uncovered SEMS in those patients. METHODS: We performed a randomized, open-label trial of participants with unresectable MBO at 20 centers in China. A total of 328 participants were allocated in parallel to the irradiation stent group (ISG) or the uncovered SEMS group (USG). Endpoints included stent patency (primary), technical success, relief of jaundice, overall survival, and complications. RESULTS: The first quartile stent patency time (when 25% of the patients experienced stent restenosis) was 212 days for the ISG and 104 days for the USG. Irradiation stents were significantly associated with a decrease in the rate of stent restenosis (9% vs. 15% at 90 days; 16% vs. 27% at 180 days; 21% vs. 33% at 360 days; p = 0.010). Patients in the ISG obtained longer survival time (median 202 days vs. 140 days; p = 0.020). No significant results were observed in technical success rate (93% vs. 95%; p = 0.499), relief of jaundice (85% vs. 80%; p = 0.308), and the incidence of grade 3 and 4 complications (8.5% vs. 7.9%; p = 0.841). CONCLUSIONS: Insertion of irradiation stents instead of uncovered SEMS could improve patency and overall survival in patients with unresectable MBO. LAY SUMMARY: For patients with unresectable malignant biliary obstruction (MBO), placement of a self-expandable metallic stent (SEMS) is a recommended palliative modality to relieve pruritus, cholangitis, pain, and jaundice. However, restenosis is a main pitfall after stent placement. Data from this first multicenter randomized controlled trial showed that insertion of an irradiation stent provided longer patency and better survival than a conventional metal stent. ClinicalTrials.gov ID: NCT02001779.

Endovascular Denervation: A New Approach for Cancer Pain Relief?

PURPOSE: To evaluate the effects of endovascular denervation (EDN) on abdominal cancer pain relief. MATERIALS AND METHODS: From April 2017 to February 2018, 7 cancer patients (2 males and 5 females) were enrolled in this study. The diagnoses of the patients included 3 pancreatic cancer, 2 cervical carcinoma, 1 cholangiocarcinoma, and 1 esophageal cancer with retroperitoneum lymph nodes invasion. Denervation was carried out at the abdominal aorta close to the origin of celiac artery and superior mesenteric artery with the use of a multielectrode radiofrequency ablation catheter with settings of time 120 seconds and temperature 60°C. The primary end point was improvement in pain scores. The secondary end points included change in quality of life, intake of narcotics, and the safety of EDN. RESULTS: All of the patients experienced pain relief. The pain scores as measured by means of visual analog scores at 1, 2, 4, 8, and 12 weeks after the procedure were significantly lower than before the operation (P < .001). A > 4 score reduction was observed in all cases. A significant reduction in narcotics use within 3 months after the operation was also seen. The quality of life scores of the patients improved significantly (P < .005) with better sleep. No severe treatment-related adverse events or major complications were observed. CONCLUSIONS: EDN is a safe and effective means to alleviate pain caused by cancer and may serve as a new approach for cancer pain relief and palliative care.

Effects of Multi-Electrode Renal Denervation on Insulin Sensitivity and Glucose Metabolism in a Canine Model of Type 2 Diabetes Mellitus.

PURPOSE: To evaluate the effects of multi-electrode catheter-based renal denervation (RDN) on insulin sensitivity and glucose metabolism in a type 2 diabetes mellitus (T2DM) canine model. MATERIALS AND METHODS: Thirty-three dogs were divided equally into 3 groups: bilateral renal denervation (BRDN) group, left renal denervation (LRDN) group, and sham operation (SHAM) group. Body weight and blood biochemistry were measured at baseline, 20 weeks, and 32 weeks, and renal angiography and computerized tomographic (CT) angiography were determined before the procedure and 1 month, 2 months, and 3 months after the procedure. Western blot was used to identify the activities of gluconeogenic enzymes and insulin-signaling proteins. RESULTS: Fasting plasma glucose (9.64 ± 1.57 mmol/L vs 5.12 ± 1.08 mmol/L; P < .0001), fasting insulin (16.19 ± 1.43 mIU/mL vs 5.07 ± 1.13 mIU/mL; P < .0001), and homeostasis-model assessment of insulin resistance (HOMA-IR; 6.95 ± 1.33 vs 1.15 ± 0.33; P < .0001) in the BRDN group had significantly decreased at the 3-month follow-up compared with the SHAM group. Western blot analyses showed that RDN suppressed the gluconeogenetic genes, modulated insulin action, and activated insulin receptors-AKT signaling cascade in the liver. CT angiography and histopathologic analyses did not show any dissection, aneurysm, thrombus, or rupture in any of the renal arteries. CONCLUSIONS: These findings identified that multi-electrode catheter-based RDN could effectively decrease gluconeogenesis and glycogenolysis, resulting in improvements in insulin sensitivity and glucose metabolism in a T2DM canine model.

Early Sorafenib-related Biomarkers for Combination Treatment with Transarterial Chemoembolization and Sorafenib in Patients with Hepatocellular Carcinoma.

Purpose To identify early biomarkers for the prediction of the therapeutic response in patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) and sorafenib (referred to as TACE plus sorafenib) and establish an effective prognostic nomogram. Materials and Methods The study was approved by the institutional ethics review boards at both participating centers. This retrospective study included all patients with HCC who underwent TACE plus sorafenib therapy between January 2010 and December 2013 at two institutions. On the basis of the overall survival (OS), early biomarkers were identified with univariate and multivariate analyses; then, a prognostic nomogram was established and internally validated by using the concordance c statistic. Results Ninety-seven patients (mean age, 55.0 years; range, 27-89 years) were included. Of these patients, 84 (86.6%) were men. The median OS was 25.7 months. After univariate and multivariate analyses, the onset of sorafenib-induced hypertension and/or dermatologic adverse events (AEs) (grade ≥2) within the first month of sorafenib initiation were demonstrated as independent predictors of OS. The median OS of patients with either of the two independent risk factors was 32.2 months, which was significantly longer than for those patients without (19.8 months; P = .005). Survival analyses showed that the earlier the AEs (sorafenib-related dermatologic AEs or hypertension) occurred, the better the outcome of the combination therapy. A prognostic nomogram was established and showed high accuracy of the nomogram with the c statistic of 0.73. Conclusion The early onset of hypertension and/or sorafenib-related dermatologic AEs are early biomarkers for the clinical prognosis of patients with HCC treated with TACE plus sorafenib. © RSNA, 2017.

Safety and Efficacy of Irradiation Stent Placement for Malignant Portal Vein Thrombus Combined with Transarterial Chemoembolization for Hepatocellular Carcinoma: A Single-Center Experience.

PURPOSE: To assess feasibility, safety, and preliminary efficacy of an irradiation portal vein stent for portal vein tumor thrombosis (PVTT) in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Between October 2012 and September 2015, 25 of 40 patients (mean age of 55.5 y) with PVTT caused by HCC were recruited for treatment with an irradiation portal vein stent (self-expandable stent loaded with iodine-125 seeds) at a single hospital. Liver function was classified as Child-Pugh class A in 15 patients (60%) and class B in 10 patients (40%). The Eastern Cooperative Oncology Group performance status score was 0 in 3 patients (12%), 1 in 13 patients (52%), and 2 in 9 patients (36%). Transarterial chemoembolization was performed after stent placement. Outcomes were measured in terms of technical success, complications, stent patency, and overall survival. RESULTS: The technical success rate was 92.0% (23/25). No complications grade 3 or higher according to Common Terminology Criteria for Adverse Events were observed. Median stent patency period was 8.0 months (range, 0.6-30.0 months). Between 7 and 955 days after stent placement, 65 cycles of transarterial chemoembolization were performed with a mean of 2.8 cycles per patient. Median survival was 12.5 months (range, 0.6-35.7 months). CONCLUSIONS: Placement of an irradiation portal vein stent appears feasible and safe and may prolong the patency of the portal vein. It is a promising technique for combining recanalization of an occluded portal vein and brachytherapy.

A Modified Model for Assessment for Retreatment with Transarterial Chemoembolization in Chinese Hepatocellular Carcinoma Patients.

PURPOSE: To develop a modified assessment for retreatment with transarterial chemoembolization (mART) score that may be more suitable for Chinese patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Chinese patients with HCC who were treated with transarterial chemoembolization in four hospitals were included. A univariate analysis and a multivariate forward Cox regression analysis were used to identify significant prognostic factors of overall survival (OS). A point scoring model was subsequently developed from the training cohort, and the validation process was performed in the validation cohort. RESULTS: The study included 259 patients (124 patients in the training cohort and 135 patients in the validation cohort). Increase in Child-Pugh scores relative to the baseline (P < .001), Barcelona Clinic Liver Cancer (BCLC) stage B before first transarterial chemoembolization (P = .001), and absence of radiologic tumor response (P < .001) were identified as negative prognostic factors for OS and were used to create the mART scores. BCLC staging was substituted for aspartate aminotransferase increase in the mART scores. The mART scores differentiated two groups with distinct prognosis by a cutoff score of 2.5 points (22.9 mo [95% confidence interval (CI), 17.4-28.4] vs 8.9 mo [95% CI, 7.5-10.3] in median survival; P < .001). In the validation cohort, the C index in assessment for retreatment with transarterial chemoembolization (ART) criteria was 0.64, whereas it was 0.82 in mART criteria. CONCLUSIONS: In Chinese patients with HCC, mART score of > 2.5 before second transarterial chemoembolization was associated with poor prognosis. The mART score was probably better validated compared with the ART score.

Conventional stents versus stents loaded with (125)iodine seeds for the treatment of unresectable oesophageal cancer: a multicentre, randomised phase 3 trial.

BACKGROUND: The combination of stent insertion and single high-dose brachytherapy is a feasible and safe palliative treatment regimen in patients with unresectable oesophageal cancer. We aimed to further assess the efficacy of this treatment strategy compared to a conventional covered stent in patients with dysphagia caused by unresectable oesophageal cancer. METHODS: In this multicentre, single-blind, randomised, phase 3 trial, we enrolled patients with unresectable oesophageal cancer from 16 hospitals in China. We included adult patients (aged ≥ 20 years) with progressive dysphagia, unresectable tumours due to extensive lesions, metastases, or poor medical condition, and with clear consciousness, cooperation, and an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-3. Eligible patients were randomly assigned (in 1:1 ratio, no stratification) to receive either a stent loaded with (125)iodine radioactive seeds (irradiation group) or a conventional oesophageal stent (control group). The primary endpoint was overall survival. Survival analyses were done in a modified intention-to-treat group. This study is registered with ClinicalTrials.gov, number NCT01054274. FINDINGS: Between Nov 1, 2009, and Oct 31, 2012, 160 patients were randomly assigned to receive treatment with either an irradiation stent (n=80) or a conventional stent (n=80). During a median follow-up of 138 days (IQR 72-207), 148 stents (73 in the irradiation group and 75 in the control group) were successfully placed into the diseased oesophagus in 148 participants. Median overall survival was 177 days (95% CI 153-201) in the irradiation group versus 147 days (124-170) in the control group (p=0.0046). Major complications and side-effects of the treatment were severe chest pain (17 [23%] of 73 patients in the irradiation group vs 15 [20%] of 75 patents in the control group), fistula formation (six [8%] vs five [7%]), aspiration pneumonia (11 [15%] vs 14 [19%]), haemorrhage (five [7%] vs five [7%]), and recurrent dysphagia (21 [28%] vs 20 [27%]). INTERPRETATION: In patients with unresectable oesophageal cancer, the insertion of an oesophageal stent loaded with (125)iodine seeds prolonged survival when compared with the insertion of a conventional covered self-expandable metallic stent.

Targeting CD300ld to normalize the tumor microenvironment: an emerging insight in cancer immunotherapy.

In a recent Nature elegant study, Wang et al. identified CD300ld, a novel functionally highly conserved tumor immunosuppressive receptor, highly expressed specifically on polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), as well as a key receptor in the regulation of recruitment and immunosuppressive function of PMN-MDSCs. Targeting CD300ld could remodel the tumor immune microenvironment, resulting in a broad-spectrum anti-tumor effect.

New First-line Immunotherapy-based Therapies for Unresectable Hepatocellular Carcinoma: A Living Network Meta-analysis.

Background and Aims: Several first-line immune checkpoint inhibitor (ICI)-based combination therapies have been identified for unresectable hepatocellular carcinoma (uHCC). This network meta-analysis (NMA) aimed to provide the most updated evidence about the preferred first-line ICI-based regimens for uHCC. Methods: A comprehensive literature search was performed in various databases from database inception to May 2022. The phase 3 trials evaluating first-line single-agent ICIs, molecular-target agents (MTAs), or their combinations in uHCC were included. The main endpoints were overall survival (OS) and progression-free survival (PFS). Pooled effect estimates were calculated using a random effects model within the frequentist framework. Subgroup analyses based on etiology were also conducted. Results: Twelve trials at low risk of bias with 8,275 patients comparing 13 treatments were included. OS with atezolizumab plus bevacizumab was comparable to sintilimab plus IBI305 [hazard ratio (HR): 1.16; 95% confidence interval (CI): 0.80-1.68] and camrelizumab plus apatinib (HR: 1.06; 95% CI: 0.75-1.51). The combination therapies, apart from atezolizumab plus cabozantinib in OS and durvalumab plus tremelimumab in PFS, had higher P-score than single-agent MTAs or ICIs. The survival benefits were associated with a high risk of adverse events leading to treatment discontinuation. The proportion of patients with hepatitis B virus-related HCC receiving ICIs combinations might positively correlate with survival advantages (R2=0.8039, p=0.0155). Conclusion: This NMA demonstrated that atezolizumab plus bevacizumab remains the stand of care and confers comparable survival benefits to sintilimab plus IBI305 and camrelizumab plus apatinib in first-line therapy for uHCC. The optimal treatment algorithms should consider efficacy, safety, and etiology.

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.

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.