Small particle drug-eluting beads-transarterial chemoembolization combined with targeted therapy in the clinical treatment of unresectable liver cancer

BACKGROUND Liver cancer is a highly malignant tumor with significant clinical impact.Chemotherapy alone often yields suboptimal outcomes in both the short and long term,characterized by high rates of local recurrence and distant metastasis,leading to a poor long-term prognosis.AIM To evaluate the clinical efficacy of small particle drug-eluting beads-transarterial chemoembolization(DEB-TACE)combined with targeted therapy for the treatment of unresectable liver cancer.METHODS We analyzed clinical data from 74 patients with unresectable liver cancer admitted between January 2019 and December 2020.Based on the different treatment regimens administered,patients were divided into the control(36 patients receiving sorafenib alone)and joint(38 patients receiving small particle DEB-TACE combined with sorafenib)groups.We compared liver function indicators[alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),albumin(ALB)]and serum tumor markers[alpha fetoprotein(AFP)]before and after treatment in both groups.Short-term efficacy measures[complete response(CR),partial response,progression disease,stable disease,objective response rate(ORR),and disease control rate(DCR)]were assessed post-treatment.Long-term follow-up evaluated median overall survival(OS),progression-free survival(PFS),and adverse reaction rates between the two groups.RESULTS One month post-treatment,the joint group demonstrated significantly higher rates of CR,ORR,and DCR compared to the control group(P<0.05).Three days after treatment,the joint group showed elevated levels of ALT,AST,and TBIL but reduced levels of ALB and AFP compared to the control group(P<0.05).The median OS was 18 months for the control group and 25 months for the joint group,while the median PFS was 15 months for the control group and 22 months for the joint group,with significant differences observed(log-rank:χ2=7.824,6.861,respectively;P=0.005,0.009,respectively).The incidence of adverse reactions was not significantly different between the groups(P>0.05).CONCLUSION The combination of small particle DEB-TACE and sorafenib significantly improves both short-and long-term outcomes in the treatment of unresectable liver cancer while preserving liver function.

Drug-eluting beads chemoembolization combined with programmed cell death 1 inhibitor and lenvatinib for large hepatocellular carcinoma

BACKGROUND The combination of transarterial chemoembolization(TACE),lenvatinib,and programmed cell death 1(PD-1)inhibitor has been widely used in the treatment of advanced hepatocellular carcinoma(HCC)and has achieved promising results.However,there are few studies comparing whether drug-eluting beads TACE(DTACE)can bring more survival benefits to patients with large HCC compared to conventional TACE(C-TACE)in this triplet therapy.AIM To compare the efficacy and adverse events(AEs)of triple therapy comprising DTACE,PD-1 inhibitors,and lenvatinib(D-TACE-P-L)and C-TACE,PD-1 inhibitors,and lenvatinib(C-TACE-P-L)in patients with large HCC(maximum diameter≥5 cm),and analyze the prognostic factors.METHODS Following a comprehensive review of our hospital’s medical records,this retrospective study included 104 patients:50 received D-TACE-P-L,and 54 received CTACE-P-L.We employed Kaplan-Meier estimation to assess the median progression-free survival(PFS)between the two groups,utilized Cox multivariate regression analysis to identify prognostic factors,and applied theχ2 test to evaluate AEs.RESULTS The objective response rate(ORR)and median PFS were significantly higher in the D-TACE-P-L group compared to the C-TACE-P-L group(ORR:66.0%vs 44.4%,P=0.027;median PFS:6.8 months vs 5.0 months,P=0.041).Cox regression analysis identified treatment option,portal vein tumor thrombus,and hepatic vein invasion as protective factors for PFS.AEs were comparable between the two CONCLUSION D-TACE-P-L may have significantly better PFS and ORR for large HCC,while exhibiting similar AEs to C-TACE-PL.

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.

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.

Efficacy of intra-arterial contrast-enhanced ultrasonography during transarterial chemoembolization with drug-eluting beads for hepatocellular carcinoma

AIM To assess the usefulness of intra-arterial contrastenhanced ultrasonography(IAUS) during transarterial chemoembolization(TACE) with drug-eluting beads(DEB) for hepatocellular carcinoma(HCC).METHODS Thirty two patients with 39 HCC underwent DEB-TACE guided with IAUS, and examined by contrast-enhanced ultrasonography(CEUS) or dynamic CT after DEB-TACE were enrolled in this study. CEUS findings before DEBTACE and IAUS findings were compared. Treatments judged to be complete and incomplete for lesions were appropriate and insufficient, respectively. Findings on CEUS and/or dynamic CT performed 1, 3 and 6 mo after DEB-TACE were evaluated using m RECIST(CR/PR/SD/PD).RESULTS The treatments were complete and incomplete in 26 and 13 lesions, respectively. On imaging evaluation using CEUS and/or dynamic CT one month after treatment, 25 and 1 lesions were judged to be CR and PR, respectively, and at 6 mo after treatment, the results were CR, PR, SD and PD for 24, 1, 0 and 1 of these lesions, respectively, in the 26 completely treated lesions. Of the 13 lesions in which treatment was incomplete, the results on imaging at one month after treatment were CR, PR, SD and PD for 0, 6, 4 and 3 lesions, respectively. The overall CR rate at 6 mo after treatment was 61.5%(24/39).CONCLUSION A combination of DEB-TACE with IAUS can improve the therapeutic effects in patients with HCC.

Transarterial chemoembolization with drug-eluting beads in hepatocellular carcinoma

Transarterial chemoembolization(TACE) is a widely used standard treatment for patients with hepatocellular carcinoma(HCC) who are not suitable candidates for curative treatments. The rationale for TACE is that intra-arterial chemotherapy using lipiodol and chemotherapeutic agents, followed by selective vascular embolization, results in a strong cytotoxic effect as well as ischemia(conventional TACE). Recently, drugeluting beads(DC Beads?) have been developed for transcatheter treatment of HCC to deliver higher doses of the chemotherapeutic agent and to prolong contact time with the tumor. DC Beads? can actively sequester doxorubicin hydrochloride from solution and release it in a controlled sustained fashion. Treatment with DC Beads? substantially reduced the amount of chemotherapeutic agent that reached the systemic circulation compared with conventional, lipiodol-based regimens, significantly reducing drug-related adverse events. In this article, we describe the treatment response, survival, and safety of TACE used with drugeluting beads for the treatment of HCC and discuss future therapeutic possibilities.

Conventional versus drug-eluting bead transarterial chemoembolization:A better option for treatment of unresectable hepatocellular carcinoma

Transarterial chemoembolization(TACE) is a minimally invasive procedure involving intra-arterial catheter-based chemotherapy to selectively administer high doses of cytotoxic drugs to the tumor bed along with ischemic necrosis induced by arterial embolization.Chemoembolization forms the essential core of management in patients with hepatocellular carcinoma(HCC) who are not suitable for curative therapies such as transplantation,resection,or percutaneous ablation.TACE of hepatic cancer(s) has proven to be helpful in achieving local tumor control,and has supported the ability to prevent tumor progression,prolong patient life,and manage patient symptoms.Recent data have demonstrated that,in patients with single-nodule HCC ≤3 cm without vascular invasion,the 5-year overall survival with TACE was found to be comparable with hepatic resection and radiofrequency ablation.Used for several years,Lipiodol continues to play a vital role as a tumor-seeking and radiopaque drug delivery vector in interventional oncology.Efforts have been made to enhance the administration of chemotherapeutic agents to tumors.Compared with conventional TACE,drug-eluting bead TACE is a fairly new drug delivery embolization technique that permits fixed dosing and has the ability to provide sustained release of anticancer agents over a period of time.The present review discusses the basic procedure of TACE and its properties,and the effectiveness of conventional and drug-eluting bead chemoembolization systems currently available or presently undergoing clinical evaluation.

Drug-eluting beads transarterial chemoembolization sequentially combined with radiofrequency ablation in the treatment of untreated and recurrent hepatocellular carcinoma

BACKGROUND Drug-eluting beads transarterial chemoem-bolization(DEB-TACE)has the advantages of slow and steady release,high local concentration,and low incidence of adverse drug reactions compared to the traditional TACE.DEBTACE combined with sequentially ultrasound-guided radiofrequency ablation(RFA)therapy has strong anti-cancer effects and little side effects,but there are fewer related long-term studies until now.AIM To explore the outcome of DEB-TACE sequentially combined with RFA for patients with primary hepatocellular carcinoma(HCC).METHODS Seventy-six patients with primary HCC who underwent DEB-TACE sequentially combined with RFA were recruited.Forty patients with untreated HCC were included in Group A,and 36 patients with recurrent HCC were included in Group B.In addition,40 patients with untreated HCC who were treated with hepatectomy were included in Group C.The serological examination,preoperative magnetic resonance imaging examination,and post-treatment computed tomography enhanced examination were performed for all patients.The efficacy was graded as complete remission(CR),partial remission(PR),stable disease and progressive disease at the 3rd,6th,and 9th.All patients were followed up for 3 years and their overall survival(OS),disease-free survival(DFS)were assessed.RESULTS The efficacy of Group A and Group C was similar(P>0.05),but the alanine aminotransferase,aspartate aminotransferase and total bilirubin of Group A were lower than those of Group C(all P<0.05).The proportions of CR(32.5%),PR(37.5%)were slightly higher than Group A(CR:27.5%,PR:35%),but the difference was not statistically significant(χ2=0.701,P=0.873).No operationalrelated deaths occurred in Group A and Group C.The OS(97.5%,84.7%,and 66.1%)and the DFS(75.0%,51.7%,and 35.4%)of Group A at the 1st,2nd,and 3rd year after treatment were similar with those of Group C(OS:90.0%,79.7%,and 63.8%;DFS:80.0%,59.7%,and 48.6%;P>0.05).The OS rates in Group A and Group B(90%,82.3%,and 66.4%)were similar(P>0.05).The DFS rates in Group B(50%,31.6%,and 17.2%)were lower than that of Group A(P=0.013).CONCLUSION The efficacy of DEA-TACE combined with RFA for untreated HCC is similar with hepatectomy.Patients with recurrent HCC could get a longer survival time through the combined treatment.

Use of Initial Modified RECIST Tumor Response Evaluation Criteria for Predicting Survival in Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization with Drug-Eluting Beads

Introduction: Transarterial chemoembolization (TACE) reduces tumor growth and increases survival in patients with hepatocellular carcinoma (HCC). Drug-eluting beads (DEB) deliver slow-release chemotherapy and reduce systemic toxicity during TACE. This study correlated initial tumor response according to modified RECIST (mRECIST) criteria and 1-year survival in patients with HCC treated with TACE-DEB, and identified predictors of tumor response. Methods: Fifty-two patients with HCC received TACE-DEB loaded with doxorubicin 75 mg during a 6-month period. Tumor response was evaluated 1 month after the procedure according to mRECIST criteria. Results: Most patients were cirrhotic and etiology of liver disease was hepatitis C in 26/52 (50%). Similar numbers of patients had Barcelona Clinic Liver Cancer (BCLC) A and BCLC B disease. Most patients had one nodule (66%). Complete response (CR) was achieved in 12/52 (23%), partial response in 19/52 (37%), stable disease in 4/52 (8%) and progressive disease in 17/52 (32%). Largest HCC ≤58 mm and BCLC stage A were associated with CR. The 1-year survival was 74%, with survival rates of 95% and 56% in the BCLC A and B groups, respectively. Variables reflecting tumor extension were associated with better survival. CR according to mRECIST criteria was a predictor of better 1-year survival (100% vs. 64%, P < 0.05). Conclusion: BCLC A and CR according to mRECIST criteria predict improved 1-year survival in patients with HCC treated with TACE-DEB. Further studies are needed to evaluate other predictors of survival and to determine if tumor response predicts long-term survival.

Transarterial chemoembolization for hepatocellular carcinoma: A review of techniques

Hepatocellular carcinoma(HCC)is one of the most common malignant diseases worldwide.While curative therapies,including resection,liver transplantation,and percutaneous ablation(percutaneous ethanol injection and radiofrequency ablation),are applicable for only a portion of the HCC population,transcatheter arterial chemoembolization(TACE)has been recognized as an effective palliative treatment option for patients with advanced HCC.TACE is also used even for single HCCs in which it is difficult to perform surgical resection or locoregional treatment due to systemic co-morbidities or anatomical problems.TACE has become widely adopted in the treatment of HCC.By using computed tomography-angiography,TACE is capable of performing diagnosis and treatment at the same time.Furthermore,TACE plays an important role in the multidisciplinary treatment for HCC when combined with other treatment.In this review,we first discuss the history of TACE,and then review the previous findings about techniques of achieving a locoregional treatment effect(liver infarction treatment,e.g.,ultra-selective TACE,balloon-occluded TACE),and the use of TACE as a drugdelivery system for anti-cancer agents(palliative,e.g.,platinum complex agents,drug-eluting beads)for multiple lesions.

Transarterial chemoembolization with pirarubicin-eluting microspheres in patients with unresectable hepatocellular carcinoma: Preliminary results

Purpose:To present the early results of pirarubicin-eluting microsphere transarterial chemoembolization(PETACE)for patients with unresectable hepatocellular carcinoma(HCC).Materials and methods:We retrospectively analyzed 55 consecutive patients with HCC who received PE-TACE between April 1,2015 and August 30,2016.The complication rate,tumor response rate,progression-free survival(PFS),and overall survival(OS)were analyzed.Results:Adverse events were generally mild and included abdominal pain and fever,although a major complication was reported in 1 patient(1.8%).During a median follow-up of 10.0 months(range,3.0-24.0 months),14 patients(25.5%)achieved a complete tumor response,25(45.5%)had a partial response,9(16.4%)showed stable disease,and 7(12.7%)had disease progression.The 1-month overall response rate was 70.9%,and the local tumor response rate was 89.0%.The 1-month tumor response rate was 100%for Barcelona Clinic Liver Cancer(BCLC)stage A or B disease and 62.8%for BCLC stage C disease.The median PFS was 6.1 months(95%confidence interval[95%CI],3.4-8.8 months;range,1.0-24.0 months).The median OS was 11.0 months(95%CI,7.1-14.9 months;range,2.0-24.0 months).Kaplan-Meier analysis(log-rank test)found significant differences in OS between patients grouped by tumor number(P=0.006),tumor size(P=0.035),and Eastern Cooperative Oncology Group(ECOG)score(P=0.005).The tumor number(1 vs.>2)was the only factor independently associated with OS(hazard ratio[HR],2.867;95%CI,1.330-6.181;P=0.007).Conclusions:PE-TACE for unresectable HCC may be safe,with favorable tumor response rates and survival time,especially in patients with a single large tumor.Longer follow-up using a larger series is necessary to confirm these preliminary results.

Transcatheter embolization therapy in liver cancer:an update of clinical evidences

Transarterial chemoembolization （TACE） is a form of intra-arterial catheter-based chemotherapy that selectively delivers high doses of cytotoxic drug to the tumor bed combining with the effect of ischemic necrosis induced by arterial embolization. Chemoembolization and radioembolization are at the core of the treatment of liver hepatocellular carcinoma （HCC） patients who cannot receive potentially curative therapies such as transplantation, resection or percutaneous ablation. TACE for liver cancer has been proven to be useful in local tumor control, to prevent tumor progression, prolong patients＇ life and control patient symptoms. Recent evidence showed in patients with single-nodule HCC of 3 cm or smaller without vascular invasion, the 5-year overall survival （OS） with TACE was similar to that with hepatic resection and radiofrequency ablation. Mthough being used for decades, Lipiodol~ （Lipiodol~ Ultra Fluid~, Guerbet, France） remains important as a tumor-seeking and radio-opaque clrug delivery vector in intervendonal oncology. There have been efforts to improve the delivery of chemotherapeutic agents to tumors. Drug-eluting bead （DEB） is a relatively novel drug delivery embolization system which allows for fixed dosing and the ability to release the anticancer agents in a sustained manner. Three DEBs are available, i.e., Tandem~ （CeloNova Biosciences Inc., USA）, DC-Beads~ （BTG, UK） and HepaSphere~ （BioSphere Medical, Inc., USA）. Transarterial radioembolization （TARE） technique has been developed, and proven to be efficient and safe in advanced liver cancers and those with vascular complications. Two types of radioembolization microspheres are available i.e., SIR-Spheres~ （Sirtex Medical Limited, Australia） and TheraSphere~ （BTG, UK）. This review describes the basic procedure of TACE, properties and efficacy of some chemoembolization systems and radioembolization agents which are commercially available and/or currently under clinical evaluation. The key clinical trials of transcatheter arterial therapy for liver cancer are summarized.

Hepatocellular carcinoma review:Current treatment,and evidence-based medicine

Hepatocellular carcinoma(HCC)is the fifth most common tumor worldwide.Multiple treatment options are available for HCC including curative resection,liver transplantation,radiofrequency ablation,trans-arterial chemoembolization,radioembolization and systemic targeted agent like sorafenib.The treatment of HCC depends on the tumor stage,patient performance status and liver function reserve and requires a multidisciplinary approach.In the past few years with significant advances in surgical treatments and locoregional therapies,the short-term survival of HCC has improved but the recurrent disease remains a big problem.The pathogenesis of HCC is a multistep and complex process,wherein angiogenesis plays an important role.For patients with advanced disease,sorafenib is the only approved therapy,but novel systemic molecular targeted agents and their combinations are emerging.This article provides an overview of treatment of early and advanced stage HCC based on our extensive review of relevant literature.