Combination treatment of transcatheter arterial chemoembolization, intensity-modulated radiotherapy, and sorafenib for hepatocellular carcinoma with macrovascular invasion.

This study evaluated the therapeutic effects and toxic reactions of combining transcatheter arterial chemoembolization (TACE) and intensity-modulated radiotherapy (IMRT) with sorafenib for the treatment of advanced hepatocellular carcinoma (HCC) patients with macrovascular invasion (MVI). We retrospectively analyzed the clinical data of 82 HCC patients with MVI, among whom 35 were treated with TACE plus IMRT alone, and 47 were treated with the combined therapy of TACE, IMRT, and sorafenib. The progression-free survival (PFS), overall survival (OS), and adverse events were assessed. The baseline characteristics were comparable between the 2 groups (all P > .05). In the TACE plus IMRT plus sorafenib group, the median PFS was 17.2 months (95% confidence interval, 14.1-19.9), significantly longer than the 9.4 months (95% confidence interval, 6.8-11.2) observed in the TACE plus IMRT group (P < .001). Additionally, patients treated with the TACE plus IMRT plus sorafenib showed a longer median OS than those treated with TACE plus IMRT alone (24.1 vs 17.3 months; P < .001). The occurrence rates of grade 1 to 2 hand-foot syndrome, other skin reactions, diarrhea, and hair loss were higher in the TACE plus IMRT plus sorafenib group (all P < .05). There were no grade 4 or higher adverse events in either group. The combination of TACE plus IMRT with sorafenib provided substantial clinical benefits in the treatment of HCC patients with MVI, increasing the tumor response rate and prolonging both PFS and OS. This approach demonstrated a tolerable and manageable safety profile.

Treatment modalities to manage hepatocellular carcinoma patients with portal vein thrombosis: a systematic review and meta-analysis.

BACKGROUND: A number of therapeutic treatment strategies exist for patients with hepatocellular carcinoma (HCC) and portal vein thrombosis (PVT). The aim of this review is to provide a current understanding of treatment options and determine the relative effectiveness of treatment options in preventing mortality over 24 months. METHODS: A search was conducted in PubMed, EMBASE and Cochrane CENTRAL from 2007 to 2022. Articles were screened to identify those that reported on all-cause mortality among treated, non-palliative patients with HCC and PVT. Study quality was assessed using the Cochrane Risk of Bias in Non-Randomized Studies of Interventions tool (ROBINS-1). Mortality rates at prespecified timepoints between 6 and 24 months were extracted and summarized using a random-effects DerSimonian-Laird model. This review was registered a priori on PROSPERO (CRD42022290708). RESULTS: When comparing radiotherapy (RT) to sorafenib and combined transarterial chemoembolization (TACE), there was a trend that RT yields better survival at 6 months [odds ratio (OR) 0.70, 95% confidence interval (CI): 0.28-1.76]. When comparing sorafenib to Y90 and RT, sorafenib was associated with higher odds for mortality at 6 months (OR 2.20, 95% CI: 1.11-4.39). No significant differences were noticed from 12 to 24 months. CONCLUSIONS: Future strategies for HCC with PVT should look at the combination of radiation and systemic treatments either concurrently or sequentially.

Efficacy and safety analysis of TACE + Donafenib + Toripalimab versus TACE + Sorafenib in the treatment of unresectable hepatocellular carcinoma: a retrospective study.

OBJECTIVE: To compare the efficacy and safety of TACE combined with Donafenib and Toripalimab versus TACE combined with Sorafenib in the treatment of unresectable hepatocellular carcinoma (HCC), aiming to guide personalized treatment strategies for HCC and improve patient prognosis. MATERIALS AND METHODS: A retrospective analysis was conducted on the clinical data of 169 patients with unresectable advanced-stage HCC who underwent treatment at the Interventional Department of Wuhan Union Hospital from January 2020 to December 2022. Based on the patients' treatment strategies, they were divided into two groups: TACE + Donafenib + Toripalimab group (N = 81) and TACE + Sorafenib group (N = 88). The primary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and progression-free survival (PFS) of the two groups' tumors. The secondary endpoint was the occurrence of treatment-related adverse events in the two groups of patients. RESULTS: The TACE + Donafenib + Toripalimab group showed higher ORR and DCR compared to the TACE + Sorafenib group (66.7% vs. 38.6%, 82.6% vs. 68.2%, P < 0.05). The TACE + Donafenib + Toripalimab group also demonstrated longer median progression-free survival (mPFS) (10.9 months vs. 7.0 months, P < 0.001) and median overall survival (mOS) (19.6 months vs. 10.9 months, P < 0.001) compared to the TACE + Sorafenib group. When comparing the two groups, the TACE + Sorafenib group had a higher incidence of grade 3-4 hypertension (14.8% vs. 4.9%, P = 0.041), higher incidence of diarrhea (all grades) (18.2% vs. 7.4%, P = 0.042), and higher incidence of hand-foot syndrome (all grades) (26.1% vs. 12.3%, P = 0.032). CONCLUSION: TACE combined with Donafenib and Toripalimab demonstrates superior efficacy and safety in treating unresectable HCC patients. This combination therapy may serve as a feasible option to improve the prognosis of unresectable HCC patients.

Efficacy and Adverse Reactions of Transcatheter Arterial Chemoembolization Combined with Apatinib in the Treatment of HCC with PVTT: A Meta-Analysis.

Background: Hepatocellular carcinoma is a major contributor to cancer-related deaths in China and ranks among the most prevalent malignant tumors. . The study aimed to assess the efficacy and adverse reactions of transcatheter arterial chemoembolization combined with apatinib in treating hepatocellular carcinoma with portal vein tumor thrombus. Methods: When treating hepatocellular carcinoma with a portal vein tumor thrombus, the computer retrieves eight databases to find controlled trials on the effects of transcatheter arterial chemoembolization combined with apatinib. The Cochrane Library, WanFang databases EMbase, PubMed, Web of Science, China Biomedical Literature Database (CBM), & CNKI are all retrieved by the computer. "Transcatheter arterial chemoembolization", "apatinib", & "hepatocellular carcinoma" are the search terms. As this a meta-analysis, Utilizing RevMan 5.3 software, data analysis was carried out following a thorough assessment of the quality of the literature. Results: This meta-analysis finally contained 7 papers. According to a meta-analysis, the disease control rate of the test category was considerably greater than that of the control category (odd Ratio OR: 1.65; 95% Cl: 1.17,2.33; P = .01). The experimental cohort's level of VEGF was substantially lower than that of the control group (standardized mean difference SMD:-25.38; 95% Cl: -28.69,-21.79; P < .01). According to a meta-analysis, caspase-8 levels in the group that underwent the experiment were substantially greater than those in the control category (SMD: 15.12; 95% Cl: 12.09, 18.15; P < .01). The test control experienced considerably less pain than the control sample (OR: 0.86; 95% Cl: 0.75,0.99; P = .033). Conclusion: The findings of this trial indicate that individuals with HCC & PVTT may benefit from TACE & apatinib together, as evidenced by disease control rate, VEGF, Caspase-8, pain, hypertension, nausea and vomiting, and more reputable studies are required to support the aforementioned conclusions.

Safety and Feasibility of Transarterial Bleomycin-Lipiodol Embolization in Patients with Giant Hepatic Hemangiomas.

Giant hepatic hemangiomas present a significant clinical challenge, and effective treatment options are warranted. This study aimed to assess the safety and feasibility of transarterial bleomycin-lipiodol embolization in patients with giant hepatic hemangiomas. A retrospective analysis was conducted on patients with giant hepatic hemangiomas (>5 cm). Transarterial chemoembolization (TACE) was performed using 7-20 cc of lipiodol mixed with 1500 IU of bleomycin. Safety outcomes, including post-embolization syndrome (PES), hepatic artery dissection, systemic complications, and access site complications, were evaluated. Radiation doses were also measured. Feasibility was assessed based on the achieved hemangioma coverage. Seventy-three patients (49 female, 24 male) with a mean age of 55.52 years were treated between December 2014 and April 2023. The average hospitalization duration was 3.82 days, and 97.3% of lesions were limited to one liver lobe. The average bleomycin dose per procedure was 1301.5625 IU, while the average lipiodol dose was 11.04 cc. The average radiation dose was 0.56 Gy. PES occurred after 45.7% of TACE procedures, with varying severity. Complications such as hepatic artery dissection (three cases), access site complications (two cases), and other complications (one case) were observed. No treatment-related mortality occurred. Hemangioma coverage exceeding 75% was achieved in 77.5% of cases. The study results suggest that transarterial bleomycin-lipiodol embolization is a safe and feasible treatment option for a heterogeneous group of patients with giant hepatic hemangiomas. This approach may hold promise in improving outcomes for patients with this challenging condition.

Chemical Shift MRI Monitoring of Chemoembolization Delivery for Hepatocellular Carcinoma: Multicenter Feasibility of Initial Clinical Translation.

Purpose To demonstrate the feasibility of using chemical shift fat-water MRI methods to visualize and measure intrahepatic delivery of ethiodized oil to liver tumors following conventional transarterial chemoembolization (cTACE). Materials and Methods Twenty-eight participants (mean age, 66 years ± 8 [SD]; 22 men) with hepatocellular carcinoma (HCC) treated with cTACE were evaluated with follow-up chemical shift MRI in this Health Insurance Portability and Accountability Act-compliant prospective, institutional review board-approved study. Uptake of ethiodized oil was evaluated at 1-month follow-up chemical shift MRI. Measurements of tumor size (MRI and CT), attenuation and enhancement (CT), fat content percentage, and tumor:normal ratio (MRI) were compared by lesion for responders versus nonresponders, as assessed with modified Response Evaluation Criteria in Solid Tumors and European Association for the Study of the Liver (EASL) criteria. Adverse events and overall survival by the Kaplan-Meier method were secondary end points. Results Focal tumor ethiodized oil retention was 46% (12 of 26 tumors) at 24 hours and 47% (18 of 38 tumors) at 1 month after cTACE. Tumor volume at CT did not differ between EASL-defined responders and nonresponders (P = .06). Tumor ethiodized oil volume measured with chemical shift MRI was statistically significantly higher for EASL-defined nonresponders (P = .02). Doxorubicin dosing (P = .53), presence of focal fat (P = .83), and a combined end point of focal fat and low doxorubicin dosing (P = .97) did not stratify overall survival after cTACE. Conclusion Chemical shift MRI allowed for assessment of tumor delivery of ethiodized oil out to 1 month after cTACE in participants with HCC and demonstrated tumor ethiodized oil volume as a potential tool for stratification of tumor response by EASL criteria. Keywords: MRI, Chemical Shift Imaging, CT, Hepatic Chemoembolization, Ethiodized Oil Clinicaltrials.gov registration no.: NCT02173119 Supplemental material is available for this article. © RSNA, 2023.

Hypersensitivity Reactions to Transarterial Chemoembolization with Cisplatin and Ethiodized Oil: A Retrospective Cohort Study.

PURPOSE: To assess the incidence of hypersensitivity reactions (HSRs) and risk factors in patients with unresectable hepatocellular carcinoma (HCC) who have undergone transarterial chemoemblization (TACE) with cisplatin-ethiodized oil emulsion. MATERIALS AND METHODS: Between September 2014 and December 2019, patients with HCC in the authors' institution undergoing TACE with cisplatin-ethiodized oil emulsion were retrospectively reviewed. Clinical, laboratory, and imaging data (including age, sex, etiology of HCC, serum bilirubin, albumin, alpha-fetoprotein, prothrombin time, dose of cisplatin, and details of TACE procedure) and data on procedural complications were retrieved from the registry of TACE. The incidence of HSRs was calculated, and variables were compared between the patient groups with and without HSRs. Predictive factors were analyzed using binary logistic regression. RESULTS: A total of 882 TACE procedures were involved in 257 patients with HCC. The median number of TACE procedures performed per patient was 3 (range, 1-23). The median dose of cisplatin per TACE session was 4.58 mg (range, 0.42-21 mg), and the median accumulated dose of cisplatin per patient was 15.42 mg (range, 0.52-125 mg). HSRs were identified in 22 (2.49%) of 882 procedures (17 [6.61%] of 257 patients). The median number of TACE procedures performed in these patients was 2.5 (range, 1-17). The median dose of cisplatin per TACE session was 5.42 mg (range, 0.63-20 mg), and the median accumulated dose of cisplatin per patient was 18.44 mg (range, 3.33-47.99 mg). Upon binary logistic regression analysis, parameters that showed statistically significant and independent association with HSRs included performance of ≥6 TACE procedures (odds ratio, 3.773; P = .012). CONCLUSIONS: Performance of ≥6 TACE procedures was found to be independently associated with the incidence of HSRs. Patients undergoing multiple TACE procedures should be monitored closely for HSRs.

Prostate arterial chemoembolization for treatment of refractory hematuria and urinary retention in patients with localized advanced prostate cancer.

OBJECTIVES: To evaluate the safety and efficacy transcatheter arterial chemoembolization (TACE) for the treatment of refractory gross hematuria (RGH) and urinary retention (UR) secondary to localized advanced prostate cancer (PCa). PATIENTS AND METHODS: Thirty-two patients (mean age 72.5 years, range 60-89) with advanced PCa-related RGH that failed conventional therapy were included. Twenty-two of these patients had catheter-dependent due to PCa-related UR. TACE was performed with epirubicin (EPI)-eluting HepaSpheres (HS) plus intra-arterial (IA) infusion of docetaxel. Technical success, adverse events (AEs), overall survival (OS), control of RGH, removal of indwelling catheters, and local disease control, were evaluated. RESULTS: Technical success was achieved in 100% without major AEs. Mean follow up post-TACE was 27 months (range 8-56 months) with a mean OS of 30 months. GRH stopped within 5 days after TACE in all patients, 26 (86.7%) of these patients exhibited good bleeding control during a mean follow-up of 24 months; 17 (77.3%) of the 22 patients with UR had recovered spontaneous urination, 15 (88.2%) patients were catheter-free at their last follow-up with a mean of 24 months. BS was obtained in 73.3% (22/30) of patients at a mean follow-up of 29 months. At the last visit, 22 patients had a mean of 36 months follow-up and the mean percentage reduction in prostate volume was 55.5%, with a statistically different from baseline (P = 0.022). Negative biopsy results were obtained in 84.2% (16/19) of the patients at 12-47 months after TACE. Compared with baseline values, there was a significant improvements in IPSS, QoL, Qmax, and PVR (all P < 0.05). CONCLUSIONS: TACE using EPI-eluting HS plus IA infusion of docetaxel is a safe and effective treatment option for the advanced PCa patients with GRH and UR, and it could be considered as an alternative if there was no other therapeutic choice.

Cidan Capsule in Combination with Adjuvant Transarterial Chemoembolization Reduces Recurrence Rate after Curative Resection of Hepatocellular Carcinoma: A Multicenter, Randomized Controlled Trial.

OBJECTIVE: To evaluate the efficacy and safety of Cidan Capsule combined with adjuvant transarterial chemoembolization (TACE) in patients with a high risk of early recurrence after curative resection of hepatocellular carcinoma (HCC). METHODS: A multicenter, randomized controlled trial was conducted in patients with high-risk recurrence factors after curative resection of HCC from 9 medical centers between July 2014 and July 2018. Totally 249 patients were randomly assigned to TACE with or without Cidan Capsule administration groups by stratified block in a 1:1 ratio. Postoperative adjuvant TACE was given 4-5 weeks after hepatic resection in both groups. Additionally, 125 patients in the TACE plus Cidan group were administrated Cidan Capsule (0.27 g/capsule, 5 capsules every time, 4 times a day) for 6 months with a 24-month follow-up. Primary endpoints included disease-free survival (DFS) and tumor recurrence rate (TRR). Secondary endpoint was overall survival (OS). Any drug-related adverse events (AEs) were observed and recorded. RESULTS: As the data cutoff in July 9th, 2018, the median DFS was not reached in the TACE plus Cidan group and 234.0 days in the TACE group (hazard ratio, 0.420, 95% confidence interval, 0.290-0.608; P<0.01). The 1- and 2-year TRR in the TACE plus Cidan and TACE groups were 31.5%, 37.1%, and 60.8%, 63.4%, respectively (P<0.01). Median OS was not reached in both groups. The 1- and 2-year OS rates in TACE plus Cidan and TACE groups were 98.4%, 98.4%, and 89.5%, 87.9%, respectively (P<0.05). The most common grade 3-4 AEs included fatigue, abdominal pain, lumbar pain, and nausea. One serious AE was reported in 1 patient in the TACE plus Cidan group, the death was due to retroperitoneal mass hemorrhage and hemorrhagic shock, and was not related to study drug. CONCLUSIONS: Cidan Capsule in combination with TACE can reduce the incidence of early recurrence in HCC patients at high-risk of recurrence after radical hepatectomy and may be an appropriate option in postoperative anti-recurrence treatment. (Registration No. NCT02253511).

Natural Products for Liver Cancer Treatment: From Traditional Medicine to Modern Drug Discovery.

Primary liver cancer was the seventh most diagnosed cancer and the second leading cause of cancer death with about 906,000 cases and 830,000 deaths, respectively, in 2020. Conventional treatment for liver cancer, such as transarterial chemoembolization (TACE) or sorafenib, has limitations in that there is the recurrence of cancer, drug inefficacy, and adverse effects. Traditional medicine and natural products of several regions including Korea, China, Europe, North America, India, and the Middle East have attracted a lot of attention since they have been reported to have anticancer effects with low adverse effects. In this review, several in vivo studies on the effects of natural compounds on liver cancer and clinical trials approving their therapeutic benefits were selected and discussed. As a result of the analysis of these studies, the effects of natural compounds were classified into a few mechanisms: apoptosis, anti-metastasis, and antiangiogenesis. In addition, medications including natural products in clinical trials were observed to exhibit improvements in various liver cancer symptoms and patients' survival rates. This study presents findings suggestive of the anticancer potential of natural products and their properties in relieving related symptoms.

Construction and Validation of Prediction Model of Severe Abdominal Pain Post-Transarterial Chemoembolization in Patients with HBV-Associated Primary Liver Cancer.

Objective: This study is aimed at constructing and evaluating a prediction model of severe abdominal pain post-transcatheter arterial chemoembolization in patients with HBV-related primary liver cancer. Methods: Patients with HBV-associated primary liver cancer who received transarterial chemoembolization (TACE) from March 2019 to March 2022 in the Interventional Therapy Department of our hospital were selected as the subjects, and the included 160 patients were randomly divided into modeling group (n = 120) and validation group (n = 40) in a ratio of 3 : 1. Visual analog scale (VAS) was used to assess pain severity. 120 patients in the modeling group were divided into no/mild abdominal pain group and severe abdominal pain group. The clinical data of the patients, including gender, age, TACE treatment history, vascular invasion, maximum diameter of tumor, infarction degree, preoperative Eastern Oncology Collaboration Group (ECOG) score, and Lipiodol dosage, were analyzed. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of the prediction model for severe abdominal pain post-TACE. Results: A total of 116 patients (72.50%) had severe abdominal pain after TACE. Univariate analysis showed that severe abdominal pain after TACE in the modeling group was associated with TACE treatment history, maximum tumor diameter, infarction degree, and preoperative ECOG score (all P < 0.05), but not related to gender, age, vascular invasion, and Lipiodol dosage (all P > 0.05). Logistic regression analysis showed that TACE treatment history, maximum tumor diameter, infarction degree, and preoperative ECOG score were all independent influencing factors for acute abdominal pain post-TACE in HBV-HCC patients (all P < 0.05). The prediction model equation was Y = -3.673 + 1.722 × TACE treatment history + 1.175 × tumor maximum diameter + 2.064 × infarction degree + 1.555 × preoperative ECOG score. Goodness-of-fit test results showed no significant difference between the established prediction model and the observed value (χ 2 = 1.645, P = 0.560) and R 2 = 0.821, suggesting that the prediction ability of the model was relatively accurate. ROC analysis results showed that the area under the curve (AUC) of severe abdominal pain after TACE was 0.916 (0.862~0.970) and 0.902 (95% CI: 0.841~0.963) in the modeling group and the verification group, respectively. Conclusion: TACE treatment history, tumor maximum diameter, infarction degree, and preoperative ECOG score are independent influencing factors for severe abdominal pain post-TACE in patients with HBV-HCC, and the prediction model established on this basis has good application value.

Imaging Diagnosis of Primary Liver Cancer Using Magnetic Resonance Dilated Weighted Imaging and the Treatment Effect of Sorafenib.

Objective: This work explores the application value of dilated weighted imaging (DWI) in the diagnosis of primary liver cancer (PLC) and the effect of sorafenib in the treatment of PLC. Methods: 88 patients with PLC who were treated in The First Affiliated Hospital of Northwest University from March 2019 to March 2021 were selected and randomly rolled into an experimental group and a control group, with 44 cases in each group. Patients in both groups were treated with transcatheter arterial chemoembolization (TACE), and the patients in the experimental group were treated with oral sorafenib on the basis of TACE. The indicators of complications, short-term efficacy (STE), and long-term efficacy (LTE) of the two groups were observed. All patients received DWI and magnetic resonance (MR) plain scan. The diagnostic accuracy and misdiagnosis rate of the two methods in diagnosing the PLC were compared. Results: The accuracy, specificity, and sensitivity of MR plain scan were 68%, 88%, and 89%, respectively, while those of DWI were 96%, 95%, and 94.2%, respectively. It indicated that the accuracy, specificity, and sensitivity of DWI in diagnosing lesions were better than those of MR plain scan, especially the diagnostic accuracy (P < 0.05). The objective response rate (ORR) and disease control rate (DCR) of the STE in the experimental group were 30% and 97%, respectively, and those in the control group were 6% and 54.5%, respectively. The experimental group's mean progression-free survival (mPFS) and mean overall survival (mOS) were 12 and 25 months, respectively, while the control group's were 8 and 19 months, respectively. It was concluded that the mPFS and mOS of patients receiving TACE combined with oral sorafenib were much higher than those receiving TACE only (P < 0.05). Conclusion: DWI and TACE combined with sorafenib had high application value in the diagnosis and treatment of PLC.

Ranking of transarterial and targeted therapies for advanced hepatocellular carcinoma in the era of immuno-oncology: A network meta-analysis of randomized sorafenib-controlled trials.

To date, no studies have compared the new first-line atezolizumab+bevacizumab with transarterial therapies combined with the prior standard-of-care, sorafenib, in patients with advanced hepatocellular carcinoma (HCC). We compared and ranked all relevant transarterial and targeted treatments competing with atezolizumab+bevacizumab for such disease, based on direct and indirect evidence. This network meta-analysis was conducted as a systematic review of phase 2 and 3 randomized sorafenib-controlled trials investigating systemic treatment strategies for HCCs unsuitable for or that progressed after surgery or locoregional treatments as first-line option published between 2008 and 2021. We ranked the treatments based on overall survival (OS) as the primary outcome, together with progression-free survival (PFS) and grade 3-4 adverse events. Subgroup analyses were also implemented to estimate intervention efficacies in particular groups. We identified 3451 publications, 15 trials consisting of 7158 patients, using 14 different therapies including combinations of sorafenib with transarterial chemoembolization (TACE), hepatic arterial chemoinfusion, and radioembolization. Regarding OS, atezolizumab+bevacizumab was the only regimen significantly superior to sorafenib (hazard ratio 0.42; 95% confidence interval [CI] 0.25-0.70), and it ranked first. This combination was also the best in the PFS analysis (0.59; 0.47-0.74), followed by lenvatinib (0.66; 0.57-0.76) and TACE+sorafenib (0.73; 0.59-0.91); all had significantly better outcomes than sorafenib alone. TACE+sorafenib (0.52; 0.27-1.00) was ranked first based on OS in a subset with portal invasion, but not in the metastatic series, with atezolizumab+bevacizumab second (0.58; 0.38-0.89). Lenvatinib (odds ratio 1.76; 95% CI 1.35-2.30) and TACE+sorafenib (2.02; 1.23-3.32), but not atezolizumab+bevacizumab (1.38; 0.93-2.05), were significantly less safe than sorafenib monotherapy. Conclusion: Our results indicate that atezolizumab+bevacizumab is the best first-line clinically relevant systemic modality in advanced HCC. TACE+sorafenib may also be considered for the disease with portal invasion. (PROSPERO No. CRD42021250701).

Clinical Outcomes of Radiological Treatment Modalities of Hepatocellular Carcinoma: A Single-Center Experience from Saudi Arabia.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver. Most patients with HCC are unsuitable for surgical therapies. Therefore, nonsurgical therapies play a central role in the management of this disease. Several percutaneous treatment modalities are available for HCC including radiofrequency ablation (RFA), transarterial chemoembolization (TACE), and transarterial radioembolization (TARE). In this study, we aim to evaluate the clinical outcomes, morbidity and mortality rates, and survival rates of four treatment modalities for HCC (RFA, TACE, TARE, and Sorafenib) and compare the success rate of each modality. METHODS: A retrospective observational study was conducted at King Abdulaziz Medical City in Jeddah, Saudi Arabia. The inclusion criteria were composed of patients diagnosed with HCC who received RFA, TACE, TARE, or Sorafenib treatments between 2008 and 2017. The primary outcome of this study was recurrence-free patients at the last follow-up. RESULTS: A total of 108 patients were included in this study. The mean age of the patients was 68.01 ± 9.98 years. Eighty-Two patients (75.9%) underwent interventions with the intention to cure or stabilize HCC, while twentysix patients (24.1%) were started on Sorafenib as a palliative treatment. The five years recurrence-free rates were 41.2% with RFA, 40% with the combination of TACE and RFA, 23.3% with TACE, and 0% with TARE. All patients on Sorafenib died from advanced-stage HCC. CONCLUSION: This study provides further evidence for the efficacy of several treatment modalities for the management of HCC. RFA and the combination of TACE and RFA showed better outcomes with a recurrence-free rate reaching up to 40%. TACE had a moderate survival benefit up to 23.3%. TARE showed negative survival benefits. Sorafenib continues to be an important palliative treatment but does not offer curative potential.

Effect of decoction of Fuzheng Jiedu Xiaoji formula plus chemoembolization on primary liver cancer in patients.

OBJECTIVE: To investigate the effect of the decoction of Fuzheng Jiedu Xiaoji formula (, FJXF) plus chemoembolization (TACE) on primary liver cancer (PLC) in patients, and study the underlying mechanism. METHODS: Patients with PLC who met the inclusion criteria were randomized into case group and control group. The case group was treated with FJXF combined with TACE. The control group was treated with TACE alone. The short-term clinical effect was evaluated; liver biochemistry, liver function index and multidrug resistance-associated indicators were detected. RESULTS: FJXF combined with TACE in the case group significantly increased the disease control rate than TACE alone in the control group (83.3% 61.1%). There was a reduction in the serum alpha-fetoprotein at 8 weeks after treatment in each group, while no difference between the two groups. The same trend can be observed for transaminase and direct bilirubin in both groups. In the case group, it showed a significant increase for albumin at 8 weeks after treatment, while no change in the control group. Multidrug resistance-associated indicators for multidrug resistance protein 1 and p-glycoprotein were upregulated in the case group but remained stable in the control group. CONCLUSIONS: FJXF combined TACE had a better short-term effect than TACE alone in patients with PLC. The potential mechanism was probably associated with alleviated multidrug resistance induced by FJXF. Additionally, FJXF didn't increase the risk of liver damage in the combined therapy.

Phase I Dose-Escalation Study of Tirapazamine Chemoembolization for Unresectable Early- and Intermediate-Stage Hepatocellular Carcinoma.

PURPOSE: To investigate the safety of replacing doxorubicin with tirapazamine in conventional transarterial chemoembolization (TACE) in an Asian population with hepatocellular carcinoma (HCC), and to determine the optimal tirapazamine dose for phase II studies. MATERIALS AND METHODS: This was a phase I, 3 + 3 dose-escalation study for patients with unresectable early- and intermediate-stage HCC who received 5, 10, or 20 mg/m2 of intra-arterial (IA) tirapazamine followed by ethiodized oil/gelatin sponge-based embolization. Key eligibilities included HCCs no more than 10 cm in diameter, prior embolization allowed, Eastern Cooperative Oncology Group performance status of 0 or 1, Child-Pugh score of 5-7, and platelet count of ≥60,000 µL. Dose-limiting toxicity (DLT) was defined as any grade 3 nonhematological or grade 4 hematological toxicity, with the exception of transient elevation of aminotransferase levels after the procedure. RESULTS: Seventeen patients were enrolled, 59% of whom had progression from a prior HCC therapy and 35% of whom had progression or recurrence after TACE. All patients tolerated the tirapazamine TACE well without any DLT or serious adverse event. Using the modified Response Evaluation Criteria in Solid Tumors, the complete response (CR) rate was 47%, and the CR + partial response rate was 65%. The median duration of response was not reached. The median time to progression was 12.6 months (95% confidence interval, 5.1-not reached). The median overall survival was 29.3 months. The selected phase II dose was set at a fixed dose of 35 mg of IA tirapazamine. CONCLUSIONS: IA tirapazamine with transarterial embolization was well tolerated and showed promising efficacy signals in intermediate-stage HCC, justifying pursuit of a phase II study.

Clinical efficacy and safety of external radiotherapy combined with sorafenib in the treatment of hepatocellular carcinoma: a systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVES: Both external radiotherapy and sorafenib are promising treatments for hepatocellular carcinoma (HCC). Nevertheless, the combined treatment of external radiotherapy and sorafenib has not been widely applied clinically due to potentially adverse effects. This meta-analysis aimed to evaluate the clinical efficacy and safety of external radiotherapy combined with sorafenib in the treatment of HCC. METHODS: Pubmed, MEDLINE, EMBASE, Cochrane Library, and Web of Science databases were searched. The primary and secondary observation endpoints were the end of survival and incidence of adverse events, respectively. 11 studies involving 664 patients were included in this meta-analysis. RESULTS: The results demonstrated that median overall survival (mOS) and median progression-free survival (mPFS) of the external radiotherapy combined with sorafenib (RS) group were 19.45 months and 8.20 months. The one- and two-year survival rates were 0.65 (95%CI: 0.55-0.76) and 0.40 (95%CI: 0.24-0.56). The incidence of adverse events was 0.34 (95%CI: 0.25-0.44). CONCLUSIONS: The findings demonstrated that the survival of the RS group was significantly improved and few severe adverse events were observed. Hence, it can be concluded that external radiotherapy combined with sorafenib is a safe, effective, and promising therapeutic option for HCC.

Combination therapy of sorafenib and drug-eluting bead transarterial chemoembolization for advanced hepatocellular carcinoma with and without hepatic arteriovenous shunt.

BACKGROUND: To compare the efficacy and safety of combination therapy with sorafenib and drug-eluting bead transarterial chemoembolization (DEB-TACE) in advanced hepatocellular carcinoma (HCC) with or without hepatic arteriovenous shunt (HAVS). METHODS: This retrospective, single-center study enrolled 59 advanced HCC patients treated with combination therapy, of whom 33 (55.9%) patients had HAVS. Tumor response according to the mRECIST criteria was evaluated based on the CT images 1 month after TACE, and changes in the arterial enhancement ratio (AER) of tumors and portal vein tumor thrombosis were also documented. Time-to-progression (TTP), overall survival (OS), and prognostic factors were analyzed. Safety was evaluated with the incidence of TACE-related complications within 6 weeks after TACE. RESULTS: The tumor response between the two groups showed no significant difference in the objective response rate (69.2% in the group without HAVS vs 60.6% in the group with HAVS, p = 0.492) or disease control rate (92.3% vs 87.9%, p = 0.685). The two groups showed comparable TTP (4.23 vs 2.33 months, p = 0.235) and OS (12.77 vs 12.97 months, p = 0.910). A drop in the AER of tumors of more than 20% on post-TACE CT independently predicted better OS. With regard to safety, there was no significant difference between the two groups. CONCLUSION: For advanced HCC, combination therapy had equal efficacy and safety in patients with HAVS compared to those without HAVS, indicating that DEB-TACE is an optional and effective treatment in these patients.

The combination of transcatheter arterial chemoembolisation (TACE) and thermal ablation versus TACE alone for hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma is the sixth most common cancer worldwide. Hepatic resection is regarded as the curative therapy for hepatocellular carcinoma. However, only about 20% of people with hepatocellular carcinoma are candidates for resection, which highlights the importance of effective nonsurgical therapies. Until now, transcatheter arterial chemoembolisation (TACE) is the most common palliative therapy for hepatocellular carcinoma, but its clinical benefits remain unsatisfactory. During recent years, some studies have reported that the combination of TACE plus thermal ablation can confer a more favourable prognosis than TACE alone. However, clear and compelling evidence to prove the beneficial or harmful effects of the combination of TACE and thermal ablation therapy is lacking. OBJECTIVES: To assess the beneficial and harmful effects of the combination of thermal ablation with TACE versus TACE alone in people with hepatocellular carcinoma. SEARCH METHODS: We performed searches in the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials in the Cochrane Library, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index-Science. We endeavoured to identify relevant randomised clinical trials also in the China National Knowledge Infrastructure (CNKI) and Wanfang databases. We searched trial registration websites for ongoing studies. We also handsearched grey literature sources. The date of last search was 22 December 2020. SELECTION CRITERIA: We planned to include all randomised clinical trials comparing the combination of TACE plus thermal ablation versus TACE alone for hepatocellular carcinoma, no matter the language, year of publication, publication status, and reported outcomes. DATA COLLECTION AND ANALYSIS: We planned to use standard methodological procedures expected by Cochrane. We planned to calculate risk ratios (RRs) with the corresponding 95% confidence intervals (CIs). For time-to-event variables, we planned to use the methods of survival analysis and express the intervention effect as a hazard ratio (HR) with 95% Cl. If the log HR and the variance were not directly reported in reports, we planned to calculate them indirectly, following methods for incorporating summary time-to-event data into meta-analysis. We planned to assess the risk of bias of the included studies using the RoB 2 tool. We planned to assess the certainty of evidence with GRADE and present the evidence in a summary of findings table. MAIN RESULTS: Out of 2224 records retrieved with the searches, we considered 135 records eligible for full-text screening. We excluded 21 of these records because the interventions used were outside the scope of our review or the studies were not randomised clinical trials. We listed the remaining 114 records, reporting on 114 studies, under studies awaiting classification because we could not be sure that these were randomised clinical trials from the information in the study paper. We could not obtain information on the registration of the study protocol for any of the 114 studies. We could not obtain information on study approval by regional research ethics committees, either from the study authors or through our own searches of trial registries. Corresponding authors did not respond to our enquiries about the design and conduct of the studies, except for one from whom we did not receive a satisfactory response. We also raised awareness of our concerns to editors of the journals that published the 114 studies, and we did not hear back with useful information. Moreover, there seemed to be inappropriate inclusion of trial participants, based on cancer stage and severity of liver disease, who should have obtained other interventions according to guidelines from learned societies. Accordingly, we found no confirmed randomised clinical trials evaluating the combination of TACE plus thermal ablation versus TACE alone for people with hepatocellular carcinoma for inclusion in our review. We identified five ongoing trials, by handsearching in clinical trial websites. AUTHORS' CONCLUSIONS: We could not find for inclusion any confirmed randomised clinical trials assessing the beneficial or harmful effects of the combination of TACE plus thermal ablation versus TACE alone in people with hepatocellular carcinoma. Therefore, our results did not show or reject the efficiency of the combination of TACE plus thermal ablation versus TACE alone for people with hepatocellular carcinoma. We need trials that compare the beneficial and harmful effects of the combination of TACE plus thermal ablation versus TACE alone in people with hepatocellular carcinoma, not eligible for treatments with curative intent (liver transplantation, ablation surgical resection) and who have sufficient liver reserve, as assessed by the Child Pugh score, and who do not have extrahepatic metastases. Therefore, future trial participants must be classified at Barcelona Clinic Liver Cancer Stage B (intermediate stage) (BCLC-B) or an equivalent, with other staging systems.

Management of hepatocellular carcinoma patients with portal vein tumor thrombosis: A narrative review.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the main reasons for malignancy-related death. Portal vein tumor thrombosis (PVTT) is the most common form of macrovascular invasion related to HCC occurring in 10%-60% of patients. HCC with PVTT is usually characterized by worsening liver function, vulnerability to blood metastasis, higher incidence of complications associated with portal hypertension, and intolerance to treatment when compared with that without PVTT. If only treated with supportive care, the median survival of HCC with PVTT is about 2.7 months. In the past, sorafenib was the only recommended therapy by guidelines with limited effectiveness. This narrative review aimed to describe the current management options for HCC with PVTT. DATA SOURCES: We have reviewed literature from PubMed on the treatment of HCC with PVTT and compiled evidence-based facts on effective therapies available for different types of PVTT. RESULTS: Sorafenib monotherapy is not much effective, but combining it with other methods can improve survival. Each type of PVTT can benefit from the combination of transarterial chemoembolization and sorafenib than sorafenib monotherapy. The tumor downstaging can be realized possibly after transarterial chemoembolization, but tumor invasion into the main trunk of the portal vein greatly impairs efficacy. Although surgery is a curative approach, it is often not recommended for Vp4 PVTT. Some new methods can broaden the indication, but further explorations are needed. Radiotherapy can decrease the possibility of Vp3 progression to Vp4, but building a forecast model of best radiation dose and response is necessary. Systemic chemotherapy, hepatic arterial infusion chemotherapy, radiofrequency ablation, portal stenting, and traditional Chinese medicine are also beneficial in Vp3-4 PVTT. The accurate diagnosis of PVTT can be made by radiomics, and prognostic classification models can be used to design personalized treatments. The application of new treatment methods such as the atezolizumab plus bevacizumab scheme may increase survival. CONCLUSIONS: HCC with PVTT is still a thorny problem, and effective therapeutics need to be explored.