Efficacy and predictive factors of transarterial chemoembolization combined with lenvatinib plus programmed cell death protein-1 inhibition for unresectable hepatocellular carcinoma

BACKGROUND The efficacy and safety of transarterial chemoembolization(TACE)combined with lenvatinib plus programmed cell death protein-1(PD-1)for unresectable hepato-cellular carcinoma(HCC)have rarely been evaluated and it is unknown which factors are related to efficacy.AIM To evaluate the efficacy and independent predictive factors of TACE combined with lenvatinib plus PD-1 inhibitors for unresectable HCC.METHODS This study retrospectively enrolled patients with unresectable HCC who received TACE/lenvatinib/PD-1 treatment between March 2019 and April 2022.Overall survival(OS)and progression-free survival(PFS)were determined.The objective response rate(ORR)and disease control rate(DCR)were evaluated in accordance with the modified Response Evaluation Criteria in Solid Tumors.Additionally,the prognostic factors affecting the clinical outcome were assessed.RESULTS One hundred and two patients were enrolled with a median follow-up duration of 12.63 months.The median OS was 26.43 months(95%CI:17.00-35.87),and the median PFS was 10.07 months(95%CI:8.50-11.65).The ORR and DCR were 61.76%and 81.37%,respectively.The patients with Barcelona Clinic Liver Cancer Classification(BCLC)B stage,early neutrophil-to-lymphocyte ratio(NLR)response(decrease),or early alpha-fetoprotein(AFP)response(decrease>20%)had superior OS and PFS than their counterparts.CONCLUSION This study showed that TACE/lenvatinib/PD-1 treatment was well tolerated with encouraging efficacy in patients with unresectable HCC.The patients with BCLC B-stage disease with early NLR response(decrease)and early AFP response(decrease>20%)may achieve better clinical outcomes with this triple therapy.

Computed tomography radiomic features and clinical factors predicting the response to first transarterial chemoembolization in intermediate-stage hepatocellular carcinoma

Background:According to clinical practice guidelines,transarterial chemoembolization(TACE)is the standard treatment modality for patients with intermediate-stage hepatocellular carcinoma(HCC).Early prediction of treatment response can help patients choose a reasonable treatment plan.This study aimed to investigate the value of the radiomic-clinical model in predicting the efficacy of the first TACE treatment for HCC to prolong patient survival.Methods:A total of 164 patients with HCC who underwent the first TACE from January 2017 to September 2021 were analyzed.The tumor response was assessed by modified response evaluation criteria in solid tumors(mRECIST),and the response of the first TACE to each session and its correlation with overall survival were evaluated.The radiomic signatures associated with the treatment response were identified by the least absolute shrinkage and selection operator(LASSO),and four machine learning models were built with different types of regions of interest(ROIs)(tumor and corresponding tissues)and the model with the best performance was selected.The predictive performance was assessed with receiver operating characteristic(ROC)curves and calibration curves.Results:Of all the models,the random forest(RF)model with peritumor(+10 mm)radiomic signatures had the best performance[area under ROC curve(AUC)=0.964 in the training cohort,AUC=0.949 in the validation cohort].The RF model was used to calculate the radiomic score(Rad-score),and the optimal cutoff value(0.34)was calculated according to the Youden’s index.Patients were then divided into a high-risk group(Rad-score>0.34)and a low-risk group(Rad-score≤0.34),and a nomogram model was successfully established to predict treatment response.The predicted treatment response also allowed for significant discrimination of Kaplan-Meier curves.Multivariate Cox regression identified six independent prognostic factors for overall survival,including male[hazard ratio(HR)=0.500,95%confidence interval(CI):0.260–0.962,P=0.038],alpha-fetoprotein(HR=1.003,95%CI:1.002–1.004,P<0.001),alanine aminotransferase(HR=1.003,95%CI:1.001–1.005,P=0.025),performance status(HR=2.400,95%CI:1.200–4.800,P=0.013),the number of TACE sessions(HR=0.870,95%CI:0.780–0.970,P=0.012)and Rad-score(HR=3.480,95%CI:1.416–8.552,P=0.007).Conclusions:The radiomic signatures and clinical factors can be well-used to predict the response of HCC patients to the first TACE and may help identify the patients most likely to benefit from TACE.

Meta-analysis of transarterial chemoembolization combined with cryoablation vs transarterial chemoembolization alone for≥5 cm hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)ranks sixth globally in cancer incidence and third in mortality rates.Unfortunately,over 70% of HCC patients forego the opportunity for curative surgery or liver transplantation due to inadequate physical examinations,poor physical condition,and limited organ availability upon diagnosis.Clinical guidelines endorse transarterial chemoembolization(TACE)as the frontline treatment for intermediate to advanced-stage HCC.Cryoablation(CRA)is an emerging local ablative therapy increasingly used in HCC management.Recent studies suggest that combining CRA with TACE offers complementary and synergistic effects,potentially improving long-term survival rates.However,the superiority of combined TACE+CRA therapy over TACE alone for HCC lesions equal to or exceeding 5 cm requires further investigation.AIM To compare the efficacy and safety of TACE combined with CRA vs TACE alone in the treatment of HCC with a diameter of≥5 cm.METHODS PubMed,EMBASE,Cochrane Library,CNKI,Wanfang,and VIP databases were searched to retrieve all relevant studies on TACE and CRA up to July 2022.Meta-analysis was performed using RevMan 5.3 software.RESULTS After screening according to the inclusion and exclusion criteria,6 articles were included,including 2 randomized controlled trials and 4 nonrandomized controlled trials,with a total of 575 patients included in the meta-analysis.The results showed that the objective response rate[odds ratio(OR)=2.56,95%confidence interval(CI):1.66-3.96,P<0.0001],disease control rate(OR=3.03,95%CI:1.88-4.89,P<0.00001),1-year survival rate(OR=3.79,95%CI:2.50-5.76,P<0.00001),2-year survival rate(OR=2.34,95%CI:1.43-3.85,P=0.0008),and 3-year survival rate(OR=3.34,95%CI:1.61-6.94,P=0.001)were all superior to those of the control group;the postoperative decrease in alpha-fetoprotein value(OR=295.53,95%CI:250.22-340.85,P<0.0001),the postoperative increase in CD4 value(OR=10.59,95%CI:8.78-12.40,P<0.00001),and the postoperative decrease in CD8 value(OR=6.47,95%CI:4.44-8.50,P<0.00001)were also significantly higher than those in the TACE-alone treatment group.CONCLUSION Compared with TACE-alone treatment,TACE+CRA combined treatment not only improves the immune function of HCC patients with a diameter of≥5 cm,but also enhances the therapeutic efficacy and long-term survival rate,without increasing the risk of complications.Therefore,TACE+CRA combined treatment may be a more recommended treatment for patients with HCC with a diameter of≥5 cm.

Drug-eluting bead transarterial chemoembolization as neoadjuvant therapy pre-liver transplantation for advanced-stage hepatocellular carcinoma

BACKGROUND The objectives of this study were to assess the safety and efficacy of drug-eluting bead transarterial chemoembolization(DEB-TACE)as neoadjuvant therapy before liver transplantation(LT)for advanced-stage hepatocellular carcinoma(HCC)and to analyze the prognostic factors.AIM To determine whether DEB-TACE before LT is superior to LT for advanced-stage HCC.METHODS A total of 99 individuals diagnosed with advanced HCC were studied retrospectively.The participants were categorized into the following two groups based on whether they had received DEB-TACE before LT:DEB-TACE group(n=45)and control group(n=54).The participants were further divided into two subgroups based on the presence or absence of segmental portal vein tumor thrombus(PVTT).The DEB-TACE group consisted of two subgroups:Group A(n=31)without PVTT and group B(n=14)with PVTT.The control group also had two subgroups:Group C(n=37)without PVTT and group D(n=17)with PVTT.Data on patient demographics,disease characteristics,therapy response,and adverse events(AEs)were collected.The overall survival(OS)and recurrence-free survival(RFS)rates were assessed using Kaplan-Meier curves.Univariate and multivariate Cox regression analyses were conducted to determine the parameters that were independently related to OS and RFS.RESULTS The DEB-TACE group exhibited an overall response rate of 86.6%.Following therapy,there was a significant decrease in the median alpha-fetoprotein(AFP)level(275.1 ng/mL vs 41.7 ng/mL,P<0.001).The main AE was post-embolization syndrome.The 2-year rates of RFS and OS were significantly higher in the DEB-TACE group than in the control group(68.9%vs 38.9%,P=0.003;86.7%vs 63.0%,P=0.008).Within the subgroups,group A had higher 2-year rates of RFS and OS compared to group C(71.0%vs 45.9%,P=0.038;83.8%vs 62.2%,P=0.047).The 2-year RFS rate of group B was markedly superior to that of group D(64.3%vs 23.5%,P=0.002).Results from multivariate analyses showed that pre-LT DEB-TACE[hazard ratio(HR)=2.73,95%confidence interval(CI):1.44-5.14,P=0.04],overall target tumor diameter≤7 cm(HR=1.98,95%CI:1.05-3.75,P=0.035),and AFP level≤400 ng/mL(HR=2.34;95%CI:1.30-4.19,P=0.009)were significant risk factors for RFS.Additionally,pre-LT DEBTACE(HR=3.15,95%CI:1.43-6.96,P=0.004)was identified as a significant risk factor for OS.CONCLUSION DEB-TACE is a safe and efficient therapy for advanced-stage HCC and also enhances patient survival after LT.

Unresectable hepatocellular carcinoma:Transarterial chemoembolization combined with lenvatinib in combination with programmed death-1 inhibition is a possible approach

In this editorial,we review the article“Efficacy and predictive factors of transarterial chemoembolization combined with lenvatinib plus programmed cell death protein-1 inhibition for unresectable hepatocellular carcinoma”.We specifically focused on whether transarterial chemoembolization combined with lenvatinib in combination with a programmed death 1 inhibitor could be used in patients with unresectable hepatocellular carcinoma.Since both transarterial chemoembolization as well as lenvatinib in combination with programmed death 1 inhibitors play an important role in the treatment of advanced liver cancer,but the combination of all three therapeutic approaches needs more research.

Paravertebral block's effect on analgesia and inflammation in advanced gastric cancer patients undergoing transarterial chemoembolization and microwave ablation

BACKGROUND Transarterial chemoembolization(TACE)combined with microwave ablation(MWA)is an effective treatment strategy for patients with advanced gastric cancer and liver metastasis.However,it may cause severe postoperative pain and inflammatory responses.The paravertebral block(PVB)is a regional anesthetic technique that provides analgesia to the thoracic and abdominal regions.AIM To evaluate the effect of PVB on postoperative analgesia and inflammatory response in patients undergoing TACE combined with MWA for advanced gastric cancer and liver metastasis.METHODS Sixty patients were randomly divided into PVB and control groups.The PVB group received ultrasound-guided PVB with 0.375%ropivacaine preoperatively,whereas the control group received intravenous analgesia with sufentanil.The primary outcome was the visual analog scale(VAS)score for pain at 6 h,12 h,24 h,and 48 h after the procedure.Secondary outcomes were the dose of sufentanil used,incidence of adverse events,and levels of inflammatory markers(white blood cell count,neutrophil percentage,C-reactive protein,and procalcitonin)before and after the procedure.RESULTS The PVB group had significantly lower VAS scores at 6 h,12 h,24 h,and 48 h after the procedure compared with the control group(P<0.05).The PVB group also had a significantly lower consumption of sufentanil and a lower incidence of nausea,vomiting,and respiratory depression than did the control group(P<0.05).Compared with the control group,the PVB group had significantly lower levels of inflammatory markers 24 h and 48 h after the procedure(P<0.05).CONCLUSION PVB can effectively reduce postoperative pain and inflammatory responses and improve postoperative comfort and recovery in patients with advanced gastric cancer and liver metastasis treated with TACE combined with MWA.

Sorafenib plus transarterial chemoembolization vs sorafenib alone for patients with advanced hepatocellular carcinoma: A systematic review and meta-analysis

BACKGROUND Although the past decade has seen remarkable advances in treatment options for hepatocellular carcinoma(HCC),the dismal overall prognosis still envelops HCC patients.Several comparative trials have been conducted to study whether transarterial chemoembolization(TACE)could improve clinical outcomes in patients receiving sorafenib for advanced HCC;however,the findings have been inconsistent.AIM To study the potential synergies and safety of sorafenib plus TACE vs sorafenib alone for treating advanced HCC,by performing a systematic review and metaanalysis.METHODS This study was conducted following the PRISMA statement.A systematic literature search was conducted using the Cochrane Library,Embase,PubMed,and Web of Science databases.Data included in the present work were collected from patients diagnosed with advanced HCC receiving sorafenib plus TACE or sorafenib alone.Data synthesis and meta-analysis were conducted using Review Manager software.RESULTS The present study included 2780 patients from five comparative clinical trials(1 was randomized control trial and 4 were retrospective studies).It was found that patients receiving sorafenib plus TACE had better prognoses in terms of overall survival(OS),with a combined hazard ratio(HR)of 0.65[95%confidence interval(95%CI):0.46–0.93,P=0.02,n=2780].Consistently,progression free survival(PFS)and time to progression(TTP)differed significantly between the sorafenib plus TACE arm and sorafenib arm(PFS:HR=0.62,95%CI:0.40–0.96,P=0.03,n=443;TTP:HR=0.73,95%CI:0.64-0.83,P<0.00001,n=2451).Disease control rate(DCR)was also significantly increased by combination therapy(risk ratio=1.36,95%CI:1.02-1.81,P=0.04,n=641).Regarding safety,the incidence of any adverse event(AE)was increased due to the addition of TACE;however,no significant difference was found in grade≥3 AEs.CONCLUSION The combination of sorafenib with TACE has superior efficacy to sorafenib monotherapy,as evidenced by prolonged OS,PFS,and TTP,as well as increased DCR.Additional high-quality trials are essential to further validate the clinical benefit of this combination in the treatment of advanced HCC.

Clinical efficacy of Gamma Knife® combined with transarterial chemoembolization and immunotherapy in the treatment of primary liver cancer

BACKGROUND This study was designed to investigate the clinical efficacy and safety of Gamma Knife®combined with transarterial chemoembolization(TACE)and immunotherapy in the treatment of primary liver cancer.AIM To investigate the clinical efficacy and safety of Gamma Knife®combined with TACE and immune-targeted therapy in the treatment of primary liver cancer.METHODS Clinical data from 51 patients with primary liver cancer admitted to our hospital between May 2018 and October 2022 were retrospectively collected.All patients underwent Gamma Knife®treatment combined with TACE and immunotherapy.The clinical efficacy,changes in liver function,overall survival(OS),and progression-free survival(PFS)of patients with different treatment responses were evaluated,and adverse reactions were recorded.RESULTS The last follow-up for this study was conducted on October 31,2023.Clinical evaluation of the 51 patients with primary liver cancer revealed a partial response(PR)in 27 patients,accounting for 52.94%(27/51);stable disease(SD)in 16 patients,accounting for 31.37%(16/51);and progressive disease(PD)in 8 patients,accounting for 15.69%(8/51).The objective response rate was 52.94%,and the disease control rate was 84.31%.Alanine aminotransferase,aspartate aminotransferase,lactate dehydrogenase,and alpha-fetoprotein isoform levels decreased after treatment compared with pretreatment(all P=0.000).The median OS was 26 months[95%confidence interval(95%CI):19.946-32.054]in the PR group and 19 months(95%CI:14.156-23.125)in the SD+PD group,with a statistically significant difference(P=0.015).The median PFS was 20 months(95%CI:18.441-34.559)in the PR group and 12 months(95%CI:8.745-13.425)in the SD+PD group,with a statistically significant difference(P=0.002).Common adverse reactions during treatment included nausea and vomiting(39.22%),thrombocytopenia(27.45%),and leukopenia(25.49%),with no treatment-related deaths reported.CONCLUSION Gamma Knife®combined with TACE and immune-targeted therapy is safe and effective in the treatment of primary liver cancer and has a good effect on improving the clinical benefit rate and liver function of patients.

Combined transarterial chemoembolization and tislelizumab for patients with unresectable hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)often presents as unresectable,necessitating effective treatment modalities.Combining transarterial chemoembolization(TACE)with immunotherapy and targeted therapy has shown promise,yet real-world evidence is needed.AIM To investigate effectiveness and safety of TACE with tislelizumab±targeted therapy for unresectable HCC in real-world setting.METHODS This retrospective study included patients with unresectable HCC receiving combined treatment of TACE and tislelizumab.The clinical outcomes included progression-free survival(PFS),overall survival(OS),objective response rate(ORR),and disease control rate(DCR).All patients were evaluated according to the mRECIST criteria.The adverse event(AE)was also assessed.RESULTS In this study of 56 patients with median follow-up of 10.9 months,7 had previous immunotherapy.Tislelizumab was administered before TACE in 21(37.50%)and after in 35(62.50%)patients,with 91.07%receiving concurrent targeted therapy.Median PFS was 14.0(95%CI:7.0-18.00)months,and OS was 28(95%CI:2.94-53.05)months.Patients with prior immunotherapy had shorter PFS(6 vs.18 months,P=0.006).Overall ORR and DCR were 82.14%and 87.50%.Grade≥3 treatment-related AEs included increased alanine aminotransferase(8.93%),aspartate aminotransferase(10.71%),and total bilirubin(3.57%).CONCLUSION The combination of TACE and tislelizumab,with or without targeted therapy,demonstrated promising efficacy and safety in unresectable HCC,especially in immunotherapy-naive patients,warranting further prospective validation studies.

Transarterial chemoembolization plus stent placement for hepatocellular carcinoma with main portal vein tumor thrombosis:A meta-analysis

BACKGROUND Portal vein tumor thrombus is an important indicator of poor prognosis in patients with hepatocellular carcinoma.Transarterial chemoembolization is recommended as the standard first-line therapy for unresectable hepatocellular carcinoma.Portal vein stent placement is a safe and effective therapy for promptly restoring flow and relieving portal hypertension caused by tumor thrombus.AIM To assess the clinical significance of transarterial chemoembolization plus stent placement for the treatment of hepatocellular carcinoma with main portal vein tumor thrombosis.METHODS We searched English and Chinese databases,assessed the quality of the included studies,analyzed the characteristic data,tested heterogeneity,explored heterogeneity,and tested publication bias.RESULTS In total,eight clinical controlled trials were included.The results showed that the pressure in the main portal vein after stent placement was significantly lower than that with no stent placement.The cumulative stent patency and survival rates at 6 and 12 months were lower in the transarterial chemoembolization+stent placement group than in the transarterial chemoembolization+stent placement+brachytherapy/radiotherapy group.The survival rates of patients treated with transarterial chemoembolization+stent placement for 6 and 12 months were higher than those of patients treated with transarterial chemoembolization alone.CONCLUSION For Chinese patients with hepatocellular carcinoma with main portal vein tumor thrombosis,transarterial chemoembolization plus stenting is effective.Transarterial chemoembolization+stent placement is more effective than transarterial chemoembolization alone.Transarterial chemoembolization+stent placement+brachytherapy/radiotherapy is more effective than transarterial chemoembolization+stenting.

Advances in Research of Post Embolism Syndrome after Transarterial Chemoembolization(TACE)for Hepatocellular Carcinoma

This article reviews the concept and clinical manifestations of post embolism syndrome after transarterial chemoembolization(TACE),and the prevention or timely intervention of post embolism syndrome in advance is expected to reduce its incidence and degree in clinical treatment,and to improve the quality of treatment of Hepatocellular Carcinoma Carcinoma(HCC).

Conventional vs drug-eluting beads transarterial chemoembolization for hepatocellular carcinoma

Transarterial chemoembolization(TACE) is the current standard of therapy for patients with intermediatestage hepatocellular carcinoma(HCC) according to the Barcelona Clinic Liver Cancer classification. The concept of conventional TACE(cTACE) is the selective obstruction of tumor-feeding artery by injection of chemotherapeutic agents, leading to ischemic necrosis of the target tumor via cytotoxic and ischemic effects. Drugeluting beads(DEBs) have been imposed as novel drugdelivering agents for TACE, which allows for higher concentrations of drugs within the target tumor and lower systemic concentrations compared with cTACE. Despite the theoretical advantages of DEB-TACE, it is still controversial in clinical practice as to whether DEBTACE is superior to cTACE in regard to overall survival and treatment response. In this review article, we summarize the clinical efficacy and safety of DEB-TACE for patients with intermediate or advanced stage HCC in comparison with cTACE.

Transarterial chemoembolization using 40 μm drug eluting beads for hepatocellular carcinoma

AIM To assess the safety and efficacy of transarterial chemoembolization(TACE) of hepatocellular carcinoma(HCC) using a new generation of 40 μm drug eluting beads in patients not eligible for curative treatment.METHODS Drug eluting bead TACE(DEB-TACE) using a new generation of microspheres(embozene tandem,40 μm) preloaded with 100 mg of doxorubicin was performed on 48 early or intermediate HCC patients with compensatedcirrhosis.Response to therapy was assessed with Response Evaluation Criteria in Solid Tumors(RECIST) and modified RECIST(m RECIST) guidelines applied to computed tomography or magnetic resonance imaging.Eleven out of the 48 treated patients treated progressed on to receive liver orthotopic transplantation(OLT).This allowed for histological analysis on the treated explanted nodules.RESULTS DEB-TACE with 40 μm showed a good safety profile without major complications or 30-d mortality.The objective response rate of treated tumors was 72.6% and 26.7% according to m RECIST and RECIST respectively.Histological examination in 11 patients assigned to OLT showed a necrosis degree > 90% in 78.6% of cases.The overall time to progression was 13 mo(11-21).CONCLUSION DEB-TACE with 40 μm particles is an effective treatment for the treatment of HCC in early-intermediate patients(Barcelona Clinic Liver Cancer stage A/B) with a good safety profile and good results in term of objective response rate and necrosis.

Computed tomography perfusion in evaluating the therapeutic effect of transarterial chemoembolization for hepatocellular carcinoma

AIM： To prospectively assess the changes in parameters of computed tomography （CT） perfusion pre- and post-transarterial chemoembolization （TACE） of hepatocellular carcinoma （HCC） in different treatment response groups, and to correlate the changes with various responses of HCC to TACE. METHODS： Thirty-nine HCC patients underwent CT perfusion examinations pre-（1 d before TACE） and post-treatment （4 wk after TACE）. The response evaluation criteria for solid tumors （RECIST） were referred to when treatment responses were distributed. Wilcoxon-signed ranks test was used to compare the differences in CT perfusion parameters pre- and post- TACE for different response groups. RESULTS： Only one case had treatment response to CR and the CT perfusion maps of post-treatment lesion displayed complete absence of signals. In the PR treatment response group, hepatic artery perfusion （HAP）, hepatic arterial fracture （HAF） and hepatic blood volume （HBV） of viable tumors post-TACE were reduced compared with pre-TACE （P = 0.001, 0.030 and 0.001, respectively）. In the SD group, all CT perfusion parameters were not significantly different pre- and post-TACE. In the PD group, HAP, HAl=, portal vein perfusion （PVP） and hepatic blood flow （HBF） of viable tumors post-TACE were significantly increased compared with pre-TACE （P = 0.005, 0.012, 0.035 and 0.005, respectively）. CONCLUSION： Changes in CT perfusion parameters of viable tumors are correlated with different responses of HCC to TACE. Therefore, CT perfusion imaging is a feasible technique for monitoring response of HCC to TACE.

Transarterial chemoembolization as initial treatment for unresectable hepatocellular carcinoma in southern China

AIM:To identify prognostic factors from pretreatment variables of the initial transarterial chemoembolization(TACE)procedure in unresectable hepatocellular carcinoma(HCC). METHODS:One thousand and five hundred and sixtynine patients with unresectable HCC underwent TACE as initial treatment were retrospectively studied.Pretreatment variables of the initial TACE procedure with a P value less than 0.05 by univariate analysis were subjected to Cox proportional hazards model. RESULTS:The median overall survival time and 1-, 5-,10-year survival rates were 10.37 mo,47%,10%, and 7%,respectively.A Cox proportional hazard model showed that 8 pretreatment factors of regional lymphnodes metastasis,Child-Pugh class,macrovascular invasion,greatest dimension,α-fetoprotein(AFP), Hepatitis virus B,tumor capsule,and nodules were independent prognostic factors.Patients with multimodality therapy have better survival than those with TACE treatment only. CONCLUSION:Tumor status,hepatic function reserve,AFP,and hepatitis virus B status were independent prognostic factors for unresectable HCC.Distant metastasis might not be a contraindication to TACE. Multimodality therapy might improve survival.

Transarterial chemoembolization and bland embolization for hepatocellular carcinoma

Transarterial chemoembolization(TACE)is the first line treatment for patients with intermediate stage hepatocellular carcinoma but is also increasingly being used for patients on the transplant waiting list to prevent further tumor growth.Despite its widespread use,TACE remains an unstandardized procedure,with variation in type and size of embolizing particles,type and dose of chemotherapy and interval between therapies.Existing evidence from randomized controlled trials suggest that bland transarterial embolization(TAE)has the same efficacy with TACE.In the current article,we review the use of TACE and TAE for hepatocellular carcinoma and we focus on the evidence for their use.

Prognostic factors for survival after transarterial chemoembolization combined with microwave ablation for hepatocellular carcinoma

AIM: To analyze prognostic factors for survival after transarterial chemoembolization (TACE) combined with microwave ablation (MWA) for hepatocellular carcinoma (HCC).

Transarterial chemoembolization using degradable starch microspheres and iodized oil in the treatment of advanced hepatocellular carcinoma: evaluation of tumor response, toxicity, and survival

BACKGROUND: In a multidisciplinary conference patients with advanced non-resectable hepatocellular carcinoma (HCC) were stratified according to their clinical status and tumor extent to different regional modalities or to best supportive care. The present study evaluated all patients who were stratified to repeated transarterial chemoembolization (TACE) from 1999 until 2003 in terms of tumor response, toxicity, and survival. A moderate embolizing approach was chosen using a combination of degradable starch microspheres (DSM) and iodized oil (Lipiodol) in order to combine anti-tumoral efficiency and low toxicity. METHODS: Fourty-seven patients were followed up prospectively. TACE treatment consisted of cisplatin (50 mg/m2), doxorubicin (50 mg/m2), 450-900 mg DSM, and 5-30 ml Lipiodol. DSM and Lipiodol were administered according to tumor vascularization. Patient characteristics,toxicity, and complications were outlined. In multivariate regression analyses of pre-treatment variables from a prospective database, predictors for tumor response and survival after TACE were determined. RESULTS: 112 TACE courses were performed (2.4±1.5 courses per patient). Mean maximum tumor size was 75 (± 43) mm, in 68% there was bilobar disease. Best response to TACE treatment was: progressive disease (PD) 9%, stable disease (SD) 55%, partial remission (PR) 36%, and complete remission (CR) 0%. Multivariate regression analyses identified tumor size ≤75 mm, tumor number ≤5, and tumor hypervascularization as predictors for PR. The overall 1-, 2-, and 3-year-survival rates were 75%, 59%, and 41%, respectively, and the median survival was 26 months. Low α-fetoprotein levels (<400 ng/ml) (Odds ratio=3.3) and PR as best response to TACE (Odds ratio=6.7) were significantly associated with long term survival (>30 months, R2=36%). Grade 3 toxicity occurred in 7.1% (n=8), and grade 4 toxicity in 3.6% (n=4) of all courses in terms of reversible leukopenia and thrombocytopenia. The incidence of major complications was 5.4% (n=6). All complications were managed conservatively. The mortality within 6 weeks after TACE was 2.1% (one patient). CONCLUSIONS: DSM and Lipiodol were combined successfully in the palliative TACE treatment of advanced HCC resulting in high rates of tumor response and survival at limited toxicity. Favourable tumor response was associated with tumor extent and vascularization. TACE using DSM and Lipiodol can be considered a suitable palliative measure in patients who might not tolerate long acting embolizing agents.

Sequential use of transarterial chemoembolization and percutaneous cryosurgery for hepatocellular carcinoma

AIM: To evaluate the efficacy of sequential use of transarterial chemoembolization (TACE) and percutaneous cryosurgery for unresectable hepatocellular carcinoma (HCC). METHODS: Four hundred and twenty patients were enrolled in this study. The patients, who were considered to have unresectable tumors due to their location or size or comorbidity, were divided into sequential TACE-cryosurgery (sequential) group (n = 290) and cryosurgery alone (cryoalone) group (n = 130). Patients in the sequential group tended to have larger tumors and a greater number of tumors than those in the cryo-alone group. Tumors larger than 10 cm in diameter were only seen in the sequential group. TACE was performed with the routine technique and percutaneous cryosurgery was conducted under the guidance of ultrasound 2-4 wk after TACE. RESULTS: During a mean follow-up period of 42 ± 17 mo (range, 24-70 mo), the local recurrence rateat the ablated area was 17% for all patients, 11% and 23% for patients in sequential group and cryoalone groups, respectively (P = 0.001). The overall 1-, 2-, 3-, 4and 5-year survival rate was 72%, 57%, 47%, 39% and 31%, respectively. The 1and 2-year survival rates (71% and 61%) in sequential group were similar to those (73% and 54%) in cryo-alone group (P = 0.69 and 0.147), while the 4and 5-year survival rates were 49% and 39% in sequential group, higher than those (29% and 23%) in cryo-alone group (P = 0.001). Eighteen patients with large HCC (> 5 cm in diameter) survived for more than 5 years after sequential TACE while no patient with large HCC (> 5 cm in diameter) survived more than 5 years after cryosurgery. The overall complication rate was 24%, and the complication rates were 21% and 26% for the sequential and cryo-alone groups, respectively (P = 0.06). The incidence of hepatic bleeding was higher in cryo-alone group than in sequential group (P = 0.02). Liver crack only occurred in two patients of the cryoalone group. CONCLUSION: Pre-cryosurgical TACE can increase the cryoablation efficacy and decrease its adverse effects, especially bleeding. Sequential TACE and cryosurgery may be the better procedure for unresectable HCC, especially for large HCC.

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

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