Trans-Arterial Chemoembolization or Bland Embolization for the Treatment of Hepatocellular Carcinoma: A Propensity Score Analysis

Trans-Arterial Chemoembolization or Bland Embolization for the Treatment of Hepatocellular Carcinoma: A Propensity Score Analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Trans-Arterial Chemoembolization or Bland Embolization for the Treatment of Hepatocellular Carcinoma: A Propensity Score Analysis Allan Ramos-Esquivel, Bruno Solis, Wilberth Araya, Esteban Garita-Rojas, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4519207/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Although Trans-Arterial Chemoembolization (TACE) is the most common procedure for the treatment of intermediate stage hepatocellular carcinoma (HCC), scarce data have demonstrated the superiority of this approach over bland embolization (TAE). Aim In this study we aimed to compare the effectiveness and liver-related complications of these two procedures through a propensity score matching (PSM) analysis. Methods We retrospectively reviewed a cohort of patients with HCC treated with first-line TAE (using Lipiodol ®) or TACE (using a chemotherapy-lipiodol emulsion or drug-eluting beads) in two referral centers between 2019 and 2021. The primary outcome was overall survival (OS). A Cox proportional hazard model was used to identify predictors for OS after adjustment using a PSM. Results A total of 114 patients were analyzed, with 73 and 41 of them receiving TACE or TAE, respectively. All included patients had diagnosis of advanced chronic liver disease, with a Child-Pugh score A in 72.8%. After a median follow-up of 17.9 months and PSM adjustment, no difference in terms of OS (HR: 1.19; 95%CI: 0.64–1.96 p = 0.69) was observed between patients receiving TACE or TAE. After multivariate analysis, only the Child-Pugh score was independently associated to OS. The frequency of liver-related complications was similar among both groups (5 vs 7.5%; p = 0.17). Conclusions After PSM, TAE and TACE provide comparable long-term outcomes and liver-related complications in patients with HCC. chemoembolization hepatocellular carcinoma propensity score Figures Figure 1 Introduction Hepatocellular carcinoma (HCC) remains the most prevalent primary liver malignancy worldwide and continues to pose a significant global health burden due to its dismal prognosis. ( 1 , 2 ) The treatment of HCC is usually a clinical challenge because of the complexity of its management and the concurrent diagnosis of chronic liver disease. ( 2 ) For patients with HCC who meet transplantation criteria, the preferred curative options are liver transplant or resection, with reported 5-year survival rates of 75–80%. ( 2 , 3 ) However, many patients receive their diagnosis at an advanced stage, precluding surgical or ablative options and leading to systemic therapies. ( 4 ) Although there is no standard treatment for unresectable HCC, patients presenting with an intermediate HCC, classified as Barcelona Clinic of Liver Cancer (BCLC) stage B, are considered good candidates for trans-arterial embolization techniques. ( 5 ) One of the hallmarks of HCC is tumoral neoangiogenesis which confers its classic pattern of arterial hypervascular enhancement and venous washout on dynamic imaging. ( 3 ) Since these tumors receive most of their blood supply through the hepatic artery, intra-arterial therapies represent the mainstay of treatment for such patients. ( 6 ) Among the available therapies, transarterial embolization (TAE) and transarterial chemoembolization (TACE) are the two main locoregional treatment options ( 3 ). Both procedures lead to tumor ischemia and inhibition of tumor growth through tumor blood flow shut down. ( 7 ) TACE involves a dual process of intra-arterial chemotherapy infusion combined with embolization, ( 6 , 7 ) aimed at selectively targeting the tumor while minimizing damage to healthy liver tissue. ( 6 ) In contrast, TAE aims to achieve the occlusion of tumor-feeding vessels without the addition of chemotherapeutic agents. ( 5 , 7 ) Both TACE and TAE induce tumor necrosis at rates in the range of 16–60%. ( 8 , 9 ) Although TACE is the most common procedure for the treatment of intermediate-stage HCC ( 3 ), scarce data from observational studies and randomized clinical trials (RCT) have demonstrated any superiority of this approach over TAE. ( 9 – 16 ) Therefore, the most effective transcatheter embolization strategy for unresectable HCC is still uncertain, as confirmed by recent meta-analyses.( 17 – 20 ) In this study, we sought to compare the effectiveness and liver-related complications of these two procedures in a real-world setting using a propensity score matching (PSM) analysis. Methods Patient selection Patients with HCC diagnosed by histology or by non-invasive criteria at imaging based on European Association for the Study of the Liver (EASL) guidelines, with a BCLC stage A or B, considered not resectable, not candidates for liver transplantation, and not amenable to ablation were retrospectively identified from electronic clinical records. We included all patients who underwent TACE or TAE as primary treatment for HCC, as indicated by a multidisciplinary tumor board (MTB) in two referral centers from January 2018 to December 2021. Patients were required to have a Child-Pugh score A or B and a performance status Eastern Cooperative Oncology Group (ECOG) 0 or 1. Patients who had one of these procedures as a bridge to liver transplantation were also selected. We excluded patients with any prior trans-arterial or local procedure. Any additional TAE/TACE or systemic therapy was recommended to some patients depending on tumor response and liver function, after discussion in the MTB. Clinical characteristics were collected from medical electronic records. Patients were followed-up with post-operative imaging (liver magnetic resonance imaging or computed tomography scan) every 4 to 6 months or clinically indicated in order to assess tumor response. The primary outcome was overall survival (OS). The safety outcome was the frequency of hepatic decompensation, defined by an increase of at least one point in the Child-Pugh score one month after the procedure. Trans-Arterial Procedures Patients were treated with trans-arterial therapy following standard local protocols. TACE using epirubicin was the standard of care for trans-arterial treatment in two hospitals, whereas TAE using lipiodol was the standard of care for patients in other. In case of TACE, 20 mg of epirubicin were either loaded on 100 µm drug-eluting beads (100 µm; Embozene Tandem® microspheres, Celonova Biosciences, Ulm, Germany), or manually emulsified with 5–10 mL of ethiodized oil (Lipiodol® Ultra Fluide, Guerbet, France) as previously described. ( 16 ) In lipiodol TACE, drug administration was immediately followed by embolization using biocompatible, hydrophilic, non-absorbable, acrylic polymer microspheres impregnated with porcine gelatin (Embosphere Merit Medical Systems, UT, USA) under fluoroscopic control. In case of TAE, 10–15 mL of pure ethiodized oil (Lipiodol® Ultra Fluide, Guerbet, was injected through the catheter as selective as possible. This procedure was followed by embolization with Embosphere ® microspheres of 300–500 um (Merit Medical Systems, UT, USA) until complete stasis of the arterial flow. Statistical analysis Descriptive categorical variables are presented as frequencies and percentages, or as means \(\pm\) standard deviations in case of continuous variables. Categorical variables were compared through the chi-square test, or Fisher test when indicated. Comparisons among baseline characteristics were performed before and after the propensity score matching. Since TAE and TACE procedures were not randomly assigned in the studied population, a PSM was used to reduce the influence of potential confounding variables between both groups. Patients were matched to receive one of these therapies based on a propensity score estimated by a multivariable logistic regression model, in which the TACE procedure was the dependent variable and the following baseline characteristics were used as covariates: Child-Pugh score, sex, and ECOG performance status. The PSM was performed with the use of a 1:1 matching without replacement (Greedy-matching algorithm). The primary outcome was overall survival (OS) as measured from the date of first TACE/TAE until death according to the National Registry System. The association between endovascular therapies (TAE or TACE) and OS was examined using a Kaplan-Meier survival curve. The log-rank test was used to compare the distributions of OS among therapies after adjustment using a PSM (1:1 greedy nearest-neighbor matching). An univariate Cox proportional-hazard regression model was used to determine the hazard ratio and its corresponding 95% confidence interval for the association between OS and the endovascular treatment received. The model was also adjusted for ECOG, Child-Pugh score, and age as covariates. The odds ratio (OR) and its 95% confidence interval was used to measure the association between liver decompensation and the trans-arterial procedure. A p value less than 0.05 was considered statistically significant. All the analyses were performed using SAS® software version 9.3 (SAS Institute Inc. Cary, NC, USA). The Institutional Review Board approved this protocol (R023-SABI-0337). Results General characteristics During the study period a total of 114 patients underwent TAE (n = 41; 35.9%) or TACE (n = 73; 64.1%). Clinical characteristics of the studied population before and after PSM are summarized in Table 1 . The majority of patients were male (n = 74, 64.9%), with a mean age of 68.5 ± 8.7 years, good performance status (ECOG 0–1: n = 102; 89.5%), and a BCLC stage of B (n = 87, 76.3%). All patients had chronic liver disease and 42.5% (n = 31) of them had clinical signs of portal hypertension. Most patients had metabolic-associated fatty liver disease (MAFLD) as underlying hepatic disease (n = 72, 63.2%). After propensity score matching, 76 patients were included in the analysis. Table 1 General characteristics of the studied population before and after the propensity score matching Variable Before PSM p value After PSM p value Trans-arterial procedure Trans-arterial procedure TAE n = 41 (35.9) TACE n = 73 (64.1) TAE n = 38 (50) TACE n = 38 (50) Sex (%) Male Female 32 (43.2) 9 (22.5) 42 (56.8) 31 (77.5) 0.03 29 (50) 9 (50) 29 (50) 9 (50) 0.99 Age (%) 70 years 0 19 (41.3) 22 (38.6) 11 (100) 27 (58.7) 35 (61.4) 0.19 0 16 (59.3) 22 (28.2) 4 (100) 11 (40.7) 23 (71.8) 0.17 ECOG (%) 0 1 28 (58.3) 13 (19.7) 20 (41.7) 53 (80.3) 0.001 26 (78.8) 12 (27.9) 7 (21.2) 31 (72.1) 0.04 Underlying liver disease (%) Alcoholic liver disease MAFLD Autoimmune hepatitis Chronic HBV Chronic HCV Other 5 (23.8) 28 (38.9) 1 (50) 2 (28.6) 3 (75) 2 (28.6) 16 (76.2) 44 (61.1) 1 (50) 5 (71.4) 1 (25) 5 (71.4) 0.44 5 (38.5) 27 (51.9) 1 (100) 2 (50) 2 (100) 1 (25) 8 (61.4) 25 (48.1) 0 2 (50) 0 3 (75) 0.45 Child-Pugh score (%) A B C 33 (39.8) 7 (23.2) 1 (100) 50 (60.2) 23 (76.7) 0 0.11 31 (50) 7 (50) 31 (50) 7 (50) 0.99 Barcelona Clinic Liver Cancer Stage (%) A B 11 (40.7) 30 (34.5) 16 (59.3) 57 (65.5) 0.55 10 (50) 10 (50) 28 (50) 28 (50) 0.99 AFP (%) > 400 ng/dl < 400 ng/dl 35 (36.8) 6 (31.6) 60 (63.2) 13 (68.4) 0.66 32 (50.8) 6 (46.2) 31 (49.2) 7 (53.8) 0.77 TAE/TACE as a bridge for liver transplantation (%) 1 ( 10 ) 9 (90) 0.09 1 (33) 2 (66) 0.56 AFP: Alpha-fetoprotein; ECOG: Eastern Cooperative Group; HBV: Hepatitis B Virus; HCV: Hepatitis C Virus; MAFLD: Metabolic associated fatty liver disease; PSM: Propensity score matching; TAE: trans-arterial embolization; TACE trans-arterial chemoembolization Efficacy and Safety outcomes After a median follow up of 17.9 months, a total of 72 patients died (63.2%). Median OS for the whole population was 19.9 months (95%CI: 15.8–26.2 months). Probability of survival at three year was 32%. As depicted in Fig. 1 , there was no significant difference between the probability of OS between patients who received TAE or TACE as endovascular treatment for HCC (HR: 1.19; 95%CI: 0.64–1.96 p = 0.69). Table 2 shows the results of the multivariate analysis for OS. After adjusting for potential confounders, only the Child-Pugh score (B vs. A) was associated with poor OS (median OS 15.5 vs. 23.3 months, respectively). Table 2 Multivariate analysis for overall survival after propensity score matching analysis Variable Hazard ratio (95% Confidence interval) p value Sex (female vs male) 0.98 (0.50–1.92) 0.95 ECOG performance status (0 vs 1) 0.52 (0.18–1.55) 0.235 Child-Pugh score (A vs B) 0.32 (0.15–0.66) 0.002* Type of treatment (TACE vs TAE) 1.68 (0.84–3.33) 0.138 ECOG: Eastern Cooperative Group ; TAE: trans-arterial embolization; TACE trans-arterial chemoembolization Hepatic decompensations occurred in 9 (23.7%) and 3 (7.9%) patients who underwent TACE and TAE, respectively (Odds ratio TACE vs . TAE: 3.7; 95%CI: 0.90-14.62; p = 0.06). Similarly, more subjects had numerically more infectious complications after TACE in comparison to those patients who received TAE with no significant differences between them (13.16 vs 5.26%; Odds Ratio: 2.27; 95%CI: 0.49–15.01; p = 0.23). Discussion The findings of our study showed comparable OS and liver-related complications among patients receiving TAE or TACE for unresectable HCC. RCTs and observational studies comparing conventional TACE and TAE have shown conflicting results to determine the superiority of one technique over the another. ( 10 – 16 ) For instance, one RCT comparing TACE, TAE, and best supportive care (BSC) was prematurely closed because of the superiority of TACE over BSC, and it was not powered enough to determine the efficacy of TACE over TAE. ( 11 ) On the other hand, another RCT concluded that the addition of cisplatin did not enhance the therapeutic effect of TAE for the treatment of patients with unresectable HCC. ( 16 ) Similarly, a recent trial also failed to show the superiority of TACE (using doxorubicin-eluting microspheres) over bland embolization. ( 14 ) Although the heterogeneity of the included patients in each trial can explain the aforementioned differences among studies, our results are in line with the null effect of chemotherapy when added to selective arterial embolization. Indeed, four recent reviews and meta-analyses found no conclusive evidence to support TAE or TACE for these patients. ( 17 – 20 ) Some authors have argued that available trials comparing bland embolization to TACE are inconclusive since they include populations that do not match the profile of patients for whom TACE would be recommended. ( 5 ) Besides, the selection criteria for these endovascular techniques are broad, from bridge or downstaging to liver transplantation to patients unsuitable for surgery. In contrast, our population was composed only by patients with a BCLC stage of A and B, for whom a MTB indicated TACE or TAE based on clinical judgment and current guidelines. ( 5 ) Hence, our results can adequately compare both procedures in a cohort of patients with a clear indication for the intravascular procedure, excluding subjects with vascular invasion, extrahepatic disease, or diffuse or extensive liver involvement. Although the relatively small sample size of this analysis can affect the precision of our findings, and the retrospective design can arise some concerns regarding selection and informative bias, we were able to provide a fair comparison between both intra-arterial procedures in a cohort of patients from a “real-world” scenario, which frequently differs from the setting of a RCT. Indeed, previous studies have indicated that selection criteria of HCC patients for intra-arterial procedures are usually broader in real clinical practice in comparison to those criteria suggested by clinical guidelines. ( 21 ) Although other cohort studies have reported similar results to ours regarding the inconclusive superiority of one of the intra-arterial procedures over the another ( 13 ), the selection of a PSM in this research enhance the comparability between both comparison arms. Given these contradictory results and the absence of superiority of one technique over the another, many authors coincide that the effects of embolic therapies derive mainly from tumor ischemia produced by occlusion of the arterial vessels and that the addition of chemotherapy have little effect on tumor control. ( 3 ) It has also been argued that TACE may incite more liver damage than bland embolization especially when conducted in a nonselective manner. Common side effects of liver embolization include fever, pain, and transient elevation of aminotransferases and bilirubin levels. More serious complications can also be present such as hepatic and kidney failure, sepsis, and death. Although our findings showed a higher percentage of patients with liver decompensation after TACE vs TAE, these differences were not statistically significant. Of note, all intra-arterial procedures were performed by well-trained interventional radiologists who prefer ultra-selective embolization in all cases when feasible, which lower the probability of side effects. Besides, the assessment of hepatic decompensation was performed one month after the procedure, and previous studies have confirmed that hepatic impairment is usually transient and self-limited. ( 22 ) The decision to use OS as a primary endpoint responds to the interobserver variation during the evaluation of response after TAE/TACE, which makes less reproductible the assessment of progression. ( 23 ) Besides, in real-world studies, OS is a more appropriate endpoint since it is less prone to information bias. In addition, some authors have argued against the use of progression-free survival as a valid surrogate efficacy outcome in patients with HCC due to its vulnerability to interpretation bias and low correlation with OS. ( 24 ) Of note, the three-year OS rate in this cohort was inferior to the reported by recent series (33% vs 55 to 66%), ( 3 ) probably because of low access to medical therapies after TAE/TACE failure. In conclusion, our findings demonstrated comparable long-term outcomes and liver-related complications in patients treated with TAE or TACE for HCC. In the absence of new RCTs comparing these two strategies, our results are useful to challenge the routine use of chemotherapy-eluting beads or lipiodol chemoembolization for the treatment of patients with BCLC-A or BCLC-B HCC. Declarations Author Contribution All authors had full access to all the data in the study and take responsibility for the integrity and accuracy of the data analysis. Study concept and design: AR & CU. Acquisition, analysis and interpretation of data: All authors Drafting of the manuscript: AR, CU. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: AR, CU. Obtaining funding: None. All authors read and approved the final manuscript Financial Support : none. There are no conflicts of interest to disclose. References Oh JH, Jun DW. The latest global burden of liver cancer: A past and present threat. Clin Mol Hepatol 2023; 29:355–7. Vogel A, Meyer T, Sapisochin G, Salem R, Saborowski A. Hepatocellular carcinoma. Lancet 2022; 400:1345-62. Sieghart W, Hucke F, Peck-Radosavljevic M. Transarterial chemoembolization: Modalities, indication, and patient selection. J Hepatol 2015; 62:1187-1195. Perfahl H, Jain HV, Joshi T, Horger M, Malek N, Bitzer M, et al. Hybrid modelling of transarterial chemoembolisation therapies (TACE) for hepatocellular carcinoma (HCC). Sci Rep 2020;10(1). doi:10.1038/s41598-020-65012-1 Reig M, Forner A, Rimola J, Ferrer-Fabrega J, Burrel M, García-Criado M, et al. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. J Hepatol 2022; 76:681-93. Galle PR, Forner A, Llovet JM, Mazzaferro V, Piscaglia F, Raoul J-L, et al. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol 2018;69:182–236. Lanza E, Donadon M, Poretti D, Pedicini V, Tramarin M, Roncalli M, et al. Transarterial therapies for hepatocellular carcinoma. Liver Cancer. 2016; 6:27–33. Burrel M, Reig M, Forner A, Barrufet M, Lope CR, Tremosini S, et al. Survival of patients with hepatocellular carcinoma treated by transarterial chemoembolisation (TACE) using drug eluting beads implications for clinical practice and trial design. J Hepatol 2012;56:1330–5. Roth GS, Benhamou M, Teyssier Y, Seigneurin A, Abousalihac M, Sengel C, et al. Comparison of trans-arterial chemoembolization and bland embolization for the treatment of hepatocellular carcinoma: A propensity score analysis. Cancers. 2021; 13:812. Kluger MD, Halazun KJ, Barroso RT, Fox AN, Olsen SK, Madoff DC, et al. Bland embolization versus chemoembolization of hepatocellular carcinoma before transplantation. Liver Transplant. 2014; 20:536–43. Llovet JM, Real MI, Montaña X, Planas R, Coll S, Aponte J, et al. Arterial embolization or chemoembolization versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: A randomised controlled trial. Lancet. 2002; 359:1734–9. Malagari K, Pomoni M, Kelekis A, et al: Prospective randomized comparison of chemoembolization with doxorubicin-eluting beads and bland embolization with BeadBlock for hepatocellular carcinoma. Cardiovasc Intervent Radiol 2010; 33:541-551. Facciorusso A, Mariani L, Sposito C, Spreafico C, Bongini M, Morosi C, et al. Drug-eluting beads versus conventional chemoembolization for the treatment of unresectable hepatocellular carcinoma. J Gastroenterol Hepatol 2016; 31:645-653. Brown KT, Do RK, Gonen M, Covey AM, Getrajdman GI, Sofocleous CT, et al. Randomized trial of hepatic artery embolization for hepatocellular carcinoma using doxorubicin-eluting microspheres compared with embolization with microspheres alone. J Clin Oncol 2016; 34: 2046–53. Meyer T. Kirkwood A. Roughton M, Beare S, Tsochatzis E, Yu D, et al. A randomised phase II/III trial of 3-weekly cisplatin-based sequential transarterial chemoembolisation vs embolisation alone for hepatocellular carcinoma. Br J Cancer 2013; 108, 1252–1259. Chang JM, Tzeng WS, Pan HB, Yang CF, Lai KH. Transcatheter arterial embolization with or without cisplatin treatment of hepatocellular carcinoma. A randomized controlled study. Cancer 1994; 74:2449-53. Lawson A, Kamarajah SK, Parente A, Pufal K, Sundareyan R, Pawlik TM, et al. Outcomes of Transarterial Embolisation (TAE) vs. Transarterial Chemoembolisation (TACE) for Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis. Cancers 2023; 15(12): 3166. Katsanos K, Kitrou P, Spiliopoulos S, Maroulis I, Petsas T, Karnabatidis D, et al. Comparative effectiveness of different transarterial embolization therapies alone or in combination with local ablative or adjuvant systemic treatments for unresectable hepatocellular carcinoma: A network meta-analysis of randomized controlled trials. Plos One 2017; 12(9): e0184597. Oliveri RS, Wetterslev J, Gluud C. Transarterial (chemo) embolization for unresectable hepatocellular carcinoma. Cochrane Database Syst Rev 2011:CD004787. Facciorusso A, Bellanti F, Villani R, Salvatore V, Muscatiello N, Piscaglia F, et al. Transarterial chemoembolization vs bland embolization in hepatocellular carcinoma: A meta-analysis of randomized trials. United European Gastroenterol J 2017; 5:511-18. Lea Leal JN, Gonen M, Covey AM, et al: Locoregional therapy for hepatocellular carcinoma with and without extrahepatic spread. J Vasc Interv Radiol 2015; 26: 1112-1121. Guo J, Wang W, Zhang Y, Xu L, Kong J. Comparison of initial tumor responses to transarterial bland embolization and drug-eluting beads-transarterial chemoembolization in the management of hepatocellular carcinoma: a propensity-score matching analysis. J Gastrointestinal Oncol 2021; 12: Gregory J, Burgio MD, Corrias G, Vilgrain V, Ronot M. Evaluation of liver tumour response by imaging. JHEP Rep. 2020, 2, 100100. Llovet JM, Montal R, Villanueva A. Randomized trials and endpoints in advanced HCC: Role of PFS as a surrogate of survival. J Hepatol 2019; 70:1262-1277. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4519207","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":315039978,"identity":"bb806c66-fc86-4392-8be6-270130c70e42","order_by":0,"name":"Allan Ramos-Esquivel","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7klEQVRIiWNgGAWjYDACduYGBOcDELOxE9LCzIjQwjgDpIWZFC3MPGCSgA7+ZsbGz4V77KL5+Q8/+2zza5s8HzMD44ePObi1SBxmbJae8Sw5d+aMNOPZuX23DduYGZglZ27DY81hxgZpngPMuRtu8DAz5/bcZgRqYWPmxaNFHmjLb54D9bkbzp9hZrbsuW1PUIvBYcY2oC2HczccyGFmZvhxO5GgFkOgFmueA8fBfmHsbbid3MbM2IzXL3LHmw/f5jlQndvPf/gxw48/t23ntzcf/PARn/dRAGMbmGwgVj0I/CFF8SgYBaNgFIwUAABO/U2mHR4VAQAAAABJRU5ErkJggg==","orcid":"","institution":"University of Costa Rica","correspondingAuthor":true,"prefix":"","firstName":"Allan","middleName":"","lastName":"Ramos-Esquivel","suffix":""},{"id":315039979,"identity":"02e1f6b6-7da7-43e8-91ee-c02e5e1e8a0d","order_by":1,"name":"Bruno Solis","email":"","orcid":"","institution":"Caja Costarricense de Seguro Social","correspondingAuthor":false,"prefix":"","firstName":"Bruno","middleName":"","lastName":"Solis","suffix":""},{"id":315039980,"identity":"886c4008-5888-4f9b-afce-d25192157be1","order_by":2,"name":"Wilberth Araya","email":"","orcid":"","institution":"Caja Costarricense de Seguro Social","correspondingAuthor":false,"prefix":"","firstName":"Wilberth","middleName":"","lastName":"Araya","suffix":""},{"id":315039981,"identity":"0eccc02a-f631-416e-93ea-2fe069bc16d7","order_by":3,"name":"Esteban Garita-Rojas","email":"","orcid":"","institution":"University of Costa Rica","correspondingAuthor":false,"prefix":"","firstName":"Esteban","middleName":"","lastName":"Garita-Rojas","suffix":""},{"id":315039982,"identity":"48cddc29-ebaa-4bd0-a545-82dc6bbd2a44","order_by":4,"name":"Ana Marenco-Flores","email":"","orcid":"","institution":"University of Costa Rica","correspondingAuthor":false,"prefix":"","firstName":"Ana","middleName":"","lastName":"Marenco-Flores","suffix":""},{"id":315039983,"identity":"153423dd-66c3-47e3-b3c0-c74406fed0e7","order_by":5,"name":"Carlos Umañan","email":"","orcid":"","institution":"Caja Costarricense de Seguro Social","correspondingAuthor":false,"prefix":"","firstName":"Carlos","middleName":"","lastName":"Umañan","suffix":""}],"badges":[],"createdAt":"2024-06-03 04:27:20","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4519207/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4519207/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":58598704,"identity":"0453e824-11c4-4eee-ab2a-8a01b47809ca","added_by":"auto","created_at":"2024-06-18 17:08:43","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":96368,"visible":true,"origin":"","legend":"\u003cp\u003eOverall survival for patients receiving trans-arterial chemoembolization (TACE) or trans-arterial embolization (TAE) according to the Kaplan-Meier method.\u003c/p\u003e","description":"","filename":"Fig1TAETACE.png","url":"https://assets-eu.researchsquare.com/files/rs-4519207/v1/c945b91324ae206c776376ba.png"},{"id":61878342,"identity":"4035d1d5-f0b0-455d-89f7-bca2432e4d15","added_by":"auto","created_at":"2024-08-06 14:48:55","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":577288,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4519207/v1/d5586b38-e7b6-42b7-ab26-287b66a5ed7a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eTrans-Arterial Chemoembolization or Bland Embolization for the Treatment of Hepatocellular Carcinoma: A Propensity Score Analysis\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHepatocellular carcinoma (HCC) remains the most prevalent primary liver malignancy worldwide and continues to pose a significant global health burden due to its dismal prognosis. (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eThe treatment of HCC is usually a clinical challenge because of the complexity of its management and the concurrent diagnosis of chronic liver disease. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) For patients with HCC who meet transplantation criteria, the preferred curative options are liver transplant or resection, with reported 5-year survival rates of 75\u0026ndash;80%. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) However, many patients receive their diagnosis at an advanced stage, precluding surgical or ablative options and leading to systemic therapies. (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) Although there is no standard treatment for unresectable HCC, patients presenting with an intermediate HCC, classified as Barcelona Clinic of Liver Cancer (BCLC) stage B, are considered good candidates for trans-arterial embolization techniques. (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eOne of the hallmarks of HCC is tumoral neoangiogenesis which confers its classic pattern of arterial hypervascular enhancement and venous washout on dynamic imaging. (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) Since these tumors receive most of their blood supply through the hepatic artery, intra-arterial therapies represent the mainstay of treatment for such patients. (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) Among the available therapies, transarterial embolization (TAE) and transarterial chemoembolization (TACE) are the two main locoregional treatment options (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Both procedures lead to tumor ischemia and inhibition of tumor growth through tumor blood flow shut down. (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) TACE involves a dual process of intra-arterial chemotherapy infusion combined with embolization, (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) aimed at selectively targeting the tumor while minimizing damage to healthy liver tissue. (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) In contrast, TAE aims to achieve the occlusion of tumor-feeding vessels without the addition of chemotherapeutic agents. (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) Both TACE and TAE induce tumor necrosis at rates in the range of 16\u0026ndash;60%. (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) Although TACE is the most common procedure for the treatment of intermediate-stage HCC (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e), scarce data from observational studies and randomized clinical trials (RCT) have demonstrated any superiority of this approach over TAE. (\u003cspan additionalcitationids=\"CR10 CR11 CR12 CR13 CR14 CR15\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) Therefore, the most effective transcatheter embolization strategy for unresectable HCC is still uncertain, as confirmed by recent meta-analyses.(\u003cspan additionalcitationids=\"CR18 CR19\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e) In this study, we sought to compare the effectiveness and liver-related complications of these two procedures in a real-world setting using a propensity score matching (PSM) analysis.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatient selection\u003c/h2\u003e \u003cp\u003e Patients with HCC diagnosed by histology or by non-invasive criteria at imaging based on European Association for the Study of the Liver (EASL) guidelines, with a BCLC stage A or B, considered not resectable, not candidates for liver transplantation, and not amenable to ablation were retrospectively identified from electronic clinical records. We included all patients who underwent TACE or TAE as primary treatment for HCC, as indicated by a multidisciplinary tumor board (MTB) in two referral centers from January 2018 to December 2021. Patients were required to have a Child-Pugh score A or B and a performance status Eastern Cooperative Oncology Group (ECOG) 0 or 1. Patients who had one of these procedures as a bridge to liver transplantation were also selected. We excluded patients with any prior trans-arterial or local procedure. Any additional TAE/TACE or systemic therapy was recommended to some patients depending on tumor response and liver function, after discussion in the MTB.\u003c/p\u003e \u003cp\u003eClinical characteristics were collected from medical electronic records. Patients were followed-up with post-operative imaging (liver magnetic resonance imaging or computed tomography scan) every 4 to 6 months or clinically indicated in order to assess tumor response. The primary outcome was overall survival (OS). The safety outcome was the frequency of hepatic decompensation, defined by an increase of at least one point in the Child-Pugh score one month after the procedure.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eTrans-Arterial Procedures\u003c/h3\u003e\n\u003cp\u003ePatients were treated with trans-arterial therapy following standard local protocols. TACE using epirubicin was the standard of care for trans-arterial treatment in two hospitals, whereas TAE using lipiodol was the standard of care for patients in other.\u003c/p\u003e \u003cp\u003eIn case of TACE, 20 mg of epirubicin were either loaded on 100 \u0026micro;m drug-eluting beads (100 \u0026micro;m; Embozene Tandem\u0026reg; microspheres, Celonova Biosciences, Ulm, Germany), or manually emulsified with 5\u0026ndash;10 mL of ethiodized oil (Lipiodol\u0026reg; Ultra Fluide, Guerbet, France) as previously described. (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) In lipiodol TACE, drug administration was immediately followed by embolization using biocompatible, hydrophilic, non-absorbable, acrylic polymer microspheres impregnated with porcine gelatin (Embosphere Merit Medical Systems, UT, USA) under fluoroscopic control.\u003c/p\u003e \u003cp\u003eIn case of TAE, 10\u0026ndash;15 mL of pure ethiodized oil (Lipiodol\u0026reg; Ultra Fluide, Guerbet, was injected through the catheter as selective as possible. This procedure was followed by embolization with Embosphere \u0026reg; microspheres of 300\u0026ndash;500 um (Merit Medical Systems, UT, USA) until complete stasis of the arterial flow.\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eDescriptive categorical variables are presented as frequencies and percentages, or as means \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\pm\\)\u003c/span\u003e\u003c/span\u003e standard deviations in case of continuous variables. Categorical variables were compared through the chi-square test, or Fisher test when indicated. Comparisons among baseline characteristics were performed before and after the propensity score matching.\u003c/p\u003e \u003cp\u003eSince TAE and TACE procedures were not randomly assigned in the studied population, a PSM was used to reduce the influence of potential confounding variables between both groups. Patients were matched to receive one of these therapies based on a propensity score estimated by a multivariable logistic regression model, in which the TACE procedure was the dependent variable and the following baseline characteristics were used as covariates: Child-Pugh score, sex, and ECOG performance status. The PSM was performed with the use of a 1:1 matching without replacement (Greedy-matching algorithm).\u003c/p\u003e \u003cp\u003eThe primary outcome was overall survival (OS) as measured from the date of first TACE/TAE until death according to the National Registry System. The association between endovascular therapies (TAE or TACE) and OS was examined using a Kaplan-Meier survival curve. The log-rank test was used to compare the distributions of OS among therapies after adjustment using a PSM (1:1 greedy nearest-neighbor matching). An univariate Cox proportional-hazard regression model was used to determine the hazard ratio and its corresponding 95% confidence interval for the association between OS and the endovascular treatment received. The model was also adjusted for ECOG, Child-Pugh score, and age as covariates. The odds ratio (OR) and its 95% confidence interval was used to measure the association between liver decompensation and the trans-arterial procedure. A \u003cem\u003ep\u003c/em\u003e value less than 0.05 was considered statistically significant. All the analyses were performed using SAS\u0026reg; software version 9.3 (SAS Institute Inc. Cary, NC, USA).\u003c/p\u003e \u003cp\u003e The Institutional Review Board approved this protocol (R023-SABI-0337).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eGeneral characteristics\u003c/h2\u003e \u003cp\u003eDuring the study period a total of 114 patients underwent TAE (n\u0026thinsp;=\u0026thinsp;41; 35.9%) or TACE (n\u0026thinsp;=\u0026thinsp;73; 64.1%). Clinical characteristics of the studied population before and after PSM are summarized in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The majority of patients were male (n\u0026thinsp;=\u0026thinsp;74, 64.9%), with a mean age of 68.5 \u0026plusmn; 8.7 years, good performance status (ECOG 0\u0026ndash;1: n\u0026thinsp;=\u0026thinsp;102; 89.5%), and a BCLC stage of B (n\u0026thinsp;=\u0026thinsp;87, 76.3%). All patients had chronic liver disease and 42.5% (n\u0026thinsp;=\u0026thinsp;31) of them had clinical signs of portal hypertension. Most patients had metabolic-associated fatty liver disease (MAFLD) as underlying hepatic disease (n\u0026thinsp;=\u0026thinsp;72, 63.2%). After propensity score matching, 76 patients were included in the analysis.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eGeneral characteristics of the studied population before and after the propensity score matching\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eBefore PSM\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eAfter PSM\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eTrans-arterial procedure\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eTrans-arterial procedure\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTAE\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;41 (35.9)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTACE\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;73 (64.1)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTAE\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;38 (50)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTACE\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;38 (50)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (%)\u003c/p\u003e \u003cp\u003eMale\u003c/p\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32 (43.2)\u003c/p\u003e \u003cp\u003e9 (22.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42 (56.8)\u003c/p\u003e \u003cp\u003e31 (77.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e29 (50)\u003c/p\u003e \u003cp\u003e9 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e29 (50)\u003c/p\u003e \u003cp\u003e9 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (%)\u003c/p\u003e \u003cp\u003e\u0026lt; 55 years\u003c/p\u003e \u003cp\u003e55\u0026ndash;70 years\u003c/p\u003e \u003cp\u003e\u0026gt; 70 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e19 (41.3)\u003c/p\u003e \u003cp\u003e22 (38.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (100)\u003c/p\u003e \u003cp\u003e27 (58.7)\u003c/p\u003e \u003cp\u003e35 (61.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e16 (59.3)\u003c/p\u003e \u003cp\u003e22 (28.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4 (100)\u003c/p\u003e \u003cp\u003e11 (40.7)\u003c/p\u003e \u003cp\u003e23 (71.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eECOG (%)\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (58.3)\u003c/p\u003e \u003cp\u003e13 (19.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (41.7)\u003c/p\u003e \u003cp\u003e53 (80.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e26 (78.8)\u003c/p\u003e \u003cp\u003e12 (27.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7 (21.2)\u003c/p\u003e \u003cp\u003e31 (72.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnderlying liver disease (%)\u003c/p\u003e \u003cp\u003eAlcoholic liver disease\u003c/p\u003e \u003cp\u003eMAFLD\u003c/p\u003e \u003cp\u003eAutoimmune hepatitis\u003c/p\u003e \u003cp\u003eChronic HBV\u003c/p\u003e \u003cp\u003eChronic HCV\u003c/p\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (23.8)\u003c/p\u003e \u003cp\u003e28 (38.9)\u003c/p\u003e \u003cp\u003e1 (50)\u003c/p\u003e \u003cp\u003e2 (28.6)\u003c/p\u003e \u003cp\u003e3 (75)\u003c/p\u003e \u003cp\u003e2 (28.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (76.2)\u003c/p\u003e \u003cp\u003e44 (61.1)\u003c/p\u003e \u003cp\u003e1 (50)\u003c/p\u003e \u003cp\u003e5 (71.4)\u003c/p\u003e \u003cp\u003e1 (25)\u003c/p\u003e \u003cp\u003e5 (71.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5 (38.5)\u003c/p\u003e \u003cp\u003e27 (51.9)\u003c/p\u003e \u003cp\u003e1 (100)\u003c/p\u003e \u003cp\u003e2 (50)\u003c/p\u003e \u003cp\u003e2 (100)\u003c/p\u003e \u003cp\u003e1 (25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8 (61.4)\u003c/p\u003e \u003cp\u003e25 (48.1)\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e2 (50)\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e3 (75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.45\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChild-Pugh score (%)\u003c/p\u003e \u003cp\u003eA\u003c/p\u003e \u003cp\u003eB\u003c/p\u003e \u003cp\u003eC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33 (39.8)\u003c/p\u003e \u003cp\u003e7 (23.2)\u003c/p\u003e \u003cp\u003e1 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50 (60.2)\u003c/p\u003e \u003cp\u003e23 (76.7)\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e31 (50)\u003c/p\u003e \u003cp\u003e7 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e31 (50)\u003c/p\u003e \u003cp\u003e7 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBarcelona Clinic Liver Cancer Stage (%)\u003c/p\u003e \u003cp\u003eA\u003c/p\u003e \u003cp\u003eB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (40.7)\u003c/p\u003e \u003cp\u003e30 (34.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (59.3)\u003c/p\u003e \u003cp\u003e57 (65.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10 (50)\u003c/p\u003e \u003cp\u003e10 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e28 (50)\u003c/p\u003e \u003cp\u003e28 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAFP (%)\u003c/p\u003e \u003cp\u003e\u0026gt; 400 ng/dl\u003c/p\u003e \u003cp\u003e\u0026lt; 400 ng/dl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35 (36.8)\u003c/p\u003e \u003cp\u003e6 (31.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60 (63.2)\u003c/p\u003e \u003cp\u003e13 (68.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e32 (50.8)\u003c/p\u003e \u003cp\u003e6 (46.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e31 (49.2)\u003c/p\u003e \u003cp\u003e7 (53.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.77\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAE/TACE as a bridge for liver transplantation (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2 (66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.56\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eAFP: Alpha-fetoprotein; ECOG: Eastern Cooperative Group; HBV: Hepatitis B Virus; HCV: Hepatitis C Virus; MAFLD: Metabolic associated fatty liver disease; PSM: Propensity score matching; TAE: trans-arterial embolization; TACE trans-arterial chemoembolization\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eEfficacy and Safety outcomes\u003c/h2\u003e \u003cp\u003eAfter a median follow up of 17.9 months, a total of 72 patients died (63.2%). Median OS for the whole population was 19.9 months (95%CI: 15.8\u0026ndash;26.2 months). Probability of survival at three year was 32%. As depicted in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, there was no significant difference between the probability of OS between patients who received TAE or TACE as endovascular treatment for HCC (HR: 1.19; 95%CI: 0.64\u0026ndash;1.96 \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.69). Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows the results of the multivariate analysis for OS. After adjusting for potential confounders, only the Child-Pugh score (B \u003cem\u003evs.\u003c/em\u003e A) was associated with poor OS (median OS 15.5 \u003cem\u003evs.\u003c/em\u003e 23.3 months, respectively).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMultivariate analysis for overall survival after propensity score matching analysis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHazard ratio (95% Confidence interval)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (female \u003cem\u003evs\u003c/em\u003e male)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.98 (0.50\u0026ndash;1.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.95\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eECOG performance status (0 \u003cem\u003evs\u003c/em\u003e 1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.52 (0.18\u0026ndash;1.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.235\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChild-Pugh score (A \u003cem\u003evs\u003c/em\u003e B)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.32 (0.15\u0026ndash;0.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.002*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of treatment (TACE \u003cem\u003evs\u003c/em\u003e TAE)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.68 (0.84\u0026ndash;3.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.138\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eECOG: Eastern Cooperative Group ; TAE: trans-arterial embolization; TACE trans-arterial chemoembolization\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eHepatic decompensations occurred in 9 (23.7%) and 3 (7.9%) patients who underwent TACE and TAE, respectively (Odds ratio TACE \u003cem\u003evs\u003c/em\u003e. TAE: 3.7; 95%CI: 0.90-14.62; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.06). Similarly, more subjects had numerically more infectious complications after TACE in comparison to those patients who received TAE with no significant differences between them (13.16 vs 5.26%; Odds Ratio: 2.27; 95%CI: 0.49\u0026ndash;15.01; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.23).\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe findings of our study showed comparable OS and liver-related complications among patients receiving TAE or TACE for unresectable HCC. RCTs and observational studies comparing conventional TACE and TAE have shown conflicting results to determine the superiority of one technique over the another. (\u003cspan additionalcitationids=\"CR11 CR12 CR13 CR14 CR15\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) For instance, one RCT comparing TACE, TAE, and best supportive care (BSC) was prematurely closed because of the superiority of TACE over BSC, and it was not powered enough to determine the efficacy of TACE over TAE. (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) On the other hand, another RCT concluded that the addition of cisplatin did not enhance the therapeutic effect of TAE for the treatment of patients with unresectable HCC. (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) Similarly, a recent trial also failed to show the superiority of TACE (using doxorubicin-eluting microspheres) over bland embolization. (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eAlthough the heterogeneity of the included patients in each trial can explain the aforementioned differences among studies, our results are in line with the null effect of chemotherapy when added to selective arterial embolization. Indeed, four recent reviews and meta-analyses found no conclusive evidence to support TAE or TACE for these patients. (\u003cspan additionalcitationids=\"CR18 CR19\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e) Some authors have argued that available trials comparing bland embolization to TACE are inconclusive since they include populations that do not match the profile of patients for whom TACE would be recommended. (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) Besides, the selection criteria for these endovascular techniques are broad, from bridge or downstaging to liver transplantation to patients unsuitable for surgery. In contrast, our population was composed only by patients with a BCLC stage of A and B, for whom a MTB indicated TACE or TAE based on clinical judgment and current guidelines. (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) Hence, our results can adequately compare both procedures in a cohort of patients with a clear indication for the intravascular procedure, excluding subjects with vascular invasion, extrahepatic disease, or diffuse or extensive liver involvement.\u003c/p\u003e \u003cp\u003eAlthough the relatively small sample size of this analysis can affect the precision of our findings, and the retrospective design can arise some concerns regarding selection and informative bias, we were able to provide a fair comparison between both intra-arterial procedures in a cohort of patients from a \u0026ldquo;real-world\u0026rdquo; scenario, which frequently differs from the setting of a RCT. Indeed, previous studies have indicated that selection criteria of HCC patients for intra-arterial procedures are usually broader in real clinical practice in comparison to those criteria suggested by clinical guidelines. (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eAlthough other cohort studies have reported similar results to ours regarding the inconclusive superiority of one of the intra-arterial procedures over the another (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e), the selection of a PSM in this research enhance the comparability between both comparison arms. Given these contradictory results and the absence of superiority of one technique over the another, many authors coincide that the effects of embolic therapies derive mainly from tumor ischemia produced by occlusion of the arterial vessels and that the addition of chemotherapy have little effect on tumor control. (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eIt has also been argued that TACE may incite more liver damage than bland embolization especially when conducted in a nonselective manner. Common side effects of liver embolization include fever, pain, and transient elevation of aminotransferases and bilirubin levels. More serious complications can also be present such as hepatic and kidney failure, sepsis, and death. Although our findings showed a higher percentage of patients with liver decompensation after TACE vs TAE, these differences were not statistically significant. Of note, all intra-arterial procedures were performed by well-trained interventional radiologists who prefer ultra-selective embolization in all cases when feasible, which lower the probability of side effects. Besides, the assessment of hepatic decompensation was performed one month after the procedure, and previous studies have confirmed that hepatic impairment is usually transient and self-limited. (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eThe decision to use OS as a primary endpoint responds to the interobserver variation during the evaluation of response after TAE/TACE, which makes less reproductible the assessment of progression. (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e) Besides, in real-world studies, OS is a more appropriate endpoint since it is less prone to information bias. In addition, some authors have argued against the use of progression-free survival as a valid surrogate efficacy outcome in patients with HCC due to its vulnerability to interpretation bias and low correlation with OS. (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eOf note, the three-year OS rate in this cohort was inferior to the reported by recent series (33% vs 55 to 66%), (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) probably because of low access to medical therapies after TAE/TACE failure.\u003c/p\u003e \u003cp\u003eIn conclusion, our findings demonstrated comparable long-term outcomes and liver-related complications in patients treated with TAE or TACE for HCC. In the absence of new RCTs comparing these two strategies, our results are useful to challenge the routine use of chemotherapy-eluting beads or lipiodol chemoembolization for the treatment of patients with BCLC-A or BCLC-B HCC.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAll authors had full access to all the data in the study and take responsibility for the integrity and accuracy of the data analysis. Study concept and design: AR \u0026amp; CU. Acquisition, analysis and interpretation of data: All authors Drafting of the manuscript: AR, CU. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: AR, CU. Obtaining funding: None. All authors read and approved the final manuscript\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eFinancial Support\u003c/strong\u003e: none.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThere are no conflicts of interest to disclose.\u003c/strong\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eOh JH, Jun DW. The latest global burden of liver cancer: A past and present threat. Clin Mol Hepatol 2023; 29:355\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eVogel A, Meyer T, Sapisochin G, Salem R, Saborowski A. Hepatocellular carcinoma. Lancet 2022; 400:1345-62.\u003c/li\u003e\n\u003cli\u003eSieghart W, Hucke F, Peck-Radosavljevic M. Transarterial chemoembolization: Modalities, indication, and patient selection. J Hepatol 2015; 62:1187-1195.\u003c/li\u003e\n\u003cli\u003ePerfahl H, Jain HV, Joshi T, Horger M, Malek N, Bitzer M, et al. Hybrid modelling of transarterial chemoembolisation therapies (TACE) for hepatocellular carcinoma (HCC). Sci Rep 2020;10(1). doi:10.1038/s41598-020-65012-1 \u003c/li\u003e\n\u003cli\u003eReig M, Forner A, Rimola J, Ferrer-Fabrega J, Burrel M, Garc\u0026iacute;a-Criado M, et al. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. J Hepatol 2022; 76:681-93.\u003c/li\u003e\n\u003cli\u003eGalle PR, Forner A, Llovet JM, Mazzaferro V, Piscaglia F, Raoul J-L, et al. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol 2018;69:182\u0026ndash;236. \u003c/li\u003e\n\u003cli\u003eLanza E, Donadon M, Poretti D, Pedicini V, Tramarin M, Roncalli M, et al. Transarterial therapies for hepatocellular carcinoma. Liver Cancer. 2016; 6:27\u0026ndash;33. \u003c/li\u003e\n\u003cli\u003eBurrel M, Reig M, Forner A, Barrufet M, Lope CR, Tremosini S, et al. Survival of patients with hepatocellular carcinoma treated by transarterial chemoembolisation (TACE) using drug eluting beads implications for clinical practice and trial design. J Hepatol 2012;56:1330\u0026ndash;5. \u003c/li\u003e\n\u003cli\u003eRoth GS, Benhamou M, Teyssier Y, Seigneurin A, Abousalihac M, Sengel C, et al. Comparison of trans-arterial chemoembolization and bland embolization for the treatment of hepatocellular carcinoma: A propensity score analysis. Cancers. 2021; 13:812. \u003c/li\u003e\n\u003cli\u003eKluger MD, Halazun KJ, Barroso RT, Fox AN, Olsen SK, Madoff DC, et al. Bland embolization versus chemoembolization of hepatocellular carcinoma before transplantation. Liver Transplant. 2014; 20:536\u0026ndash;43. \u003c/li\u003e\n\u003cli\u003eLlovet JM, Real MI, Monta\u0026ntilde;a X, Planas R, Coll S, Aponte J, et al. Arterial embolization or chemoembolization versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: A randomised controlled trial. Lancet. 2002; 359:1734\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eMalagari K, Pomoni M, Kelekis A, et al: Prospective randomized comparison of chemoembolization with doxorubicin-eluting beads and bland embolization with BeadBlock for hepatocellular carcinoma. Cardiovasc Intervent Radiol 2010; 33:541-551.\u003c/li\u003e\n\u003cli\u003eFacciorusso A, Mariani L, Sposito C, Spreafico C, Bongini M, Morosi C, et al. Drug-eluting beads versus conventional chemoembolization for the treatment of unresectable hepatocellular carcinoma. J Gastroenterol Hepatol 2016; 31:645-653.\u003c/li\u003e\n\u003cli\u003eBrown KT, Do RK, Gonen M, Covey AM, Getrajdman GI, Sofocleous CT, et al. Randomized trial of hepatic artery embolization for hepatocellular carcinoma using doxorubicin-eluting microspheres compared with embolization with microspheres alone. J Clin Oncol 2016; 34: 2046\u0026ndash;53. \u003c/li\u003e\n\u003cli\u003eMeyer T. Kirkwood A. Roughton M, Beare S, Tsochatzis E, Yu D, et al. A randomised phase II/III trial of 3-weekly cisplatin-based sequential transarterial chemoembolisation vs embolisation alone for hepatocellular carcinoma. Br J Cancer 2013; 108, 1252\u0026ndash;1259.\u003c/li\u003e\n\u003cli\u003eChang JM, Tzeng WS, Pan HB, Yang CF, Lai KH. Transcatheter arterial embolization with or without cisplatin treatment of hepatocellular carcinoma. A randomized controlled study. Cancer 1994; 74:2449-53. \u003c/li\u003e\n\u003cli\u003eLawson A, Kamarajah SK, Parente A, Pufal K, Sundareyan R, Pawlik TM, et al. Outcomes of Transarterial Embolisation (TAE) vs. Transarterial Chemoembolisation (TACE) for Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis. Cancers 2023; 15(12): 3166.\u003c/li\u003e\n\u003cli\u003eKatsanos K, Kitrou P, Spiliopoulos S, Maroulis I, Petsas T, Karnabatidis D, et al. Comparative effectiveness of different transarterial embolization therapies alone or in combination with local ablative or adjuvant systemic treatments for unresectable hepatocellular carcinoma: A network meta-analysis of randomized controlled trials. Plos One 2017; 12(9): e0184597.\u003c/li\u003e\n\u003cli\u003eOliveri RS, Wetterslev J, Gluud C. Transarterial (chemo) embolization for unresectable hepatocellular carcinoma. Cochrane Database Syst Rev 2011:CD004787.\u003c/li\u003e\n\u003cli\u003eFacciorusso A, Bellanti F, Villani R, Salvatore V, Muscatiello N, Piscaglia F, et al. Transarterial chemoembolization vs bland embolization in hepatocellular carcinoma: A meta-analysis of randomized trials. United European Gastroenterol J 2017; 5:511-18. \u003c/li\u003e\n\u003cli\u003eLea Leal JN, Gonen M, Covey AM, et al: Locoregional therapy for hepatocellular carcinoma with and without extrahepatic spread. J Vasc Interv Radiol 2015; 26: 1112-1121.\u003c/li\u003e\n\u003cli\u003eGuo J, Wang W, Zhang Y, Xu L, Kong J. Comparison of initial tumor responses to transarterial bland embolization and drug-eluting beads-transarterial chemoembolization in the management of hepatocellular carcinoma: a propensity-score matching analysis. J Gastrointestinal Oncol 2021; 12:\u003c/li\u003e\n\u003cli\u003eGregory J, Burgio MD, Corrias G, Vilgrain V, Ronot M. Evaluation of liver tumour response by imaging. JHEP Rep. 2020, 2, 100100.\u003c/li\u003e\n\u003cli\u003eLlovet JM, Montal R, Villanueva A. Randomized trials and endpoints in advanced HCC: Role of PFS as a surrogate of survival. J Hepatol 2019; 70:1262-1277.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"chemoembolization, hepatocellular carcinoma, propensity score","lastPublishedDoi":"10.21203/rs.3.rs-4519207/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4519207/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eAlthough Trans-Arterial Chemoembolization (TACE) is the most common procedure for the treatment of intermediate stage hepatocellular carcinoma (HCC), scarce data have demonstrated the superiority of this approach over bland embolization (TAE).\u003c/p\u003e\u003ch2\u003eAim\u003c/h2\u003e \u003cp\u003eIn this study we aimed to compare the effectiveness and liver-related complications of these two procedures through a propensity score matching (PSM) analysis.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe retrospectively reviewed a cohort of patients with HCC treated with first-line TAE (using Lipiodol \u0026reg;) or TACE (using a chemotherapy-lipiodol emulsion or drug-eluting beads) in two referral centers between 2019 and 2021. The primary outcome was overall survival (OS). A Cox proportional hazard model was used to identify predictors for OS after adjustment using a PSM.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 114 patients were analyzed, with 73 and 41 of them receiving TACE or TAE, respectively. All included patients had diagnosis of advanced chronic liver disease, with a Child-Pugh score A in 72.8%. After a median follow-up of 17.9 months and PSM adjustment, no difference in terms of OS (HR: 1.19; 95%CI: 0.64\u0026ndash;1.96 \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.69) was observed between patients receiving TACE or TAE. After multivariate analysis, only the Child-Pugh score was independently associated to OS. The frequency of liver-related complications was similar among both groups (5 vs 7.5%; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.17).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eAfter PSM, TAE and TACE provide comparable long-term outcomes and liver-related complications in patients with HCC.\u003c/p\u003e","manuscriptTitle":"Trans-Arterial Chemoembolization or Bland Embolization for the Treatment of Hepatocellular Carcinoma: A Propensity Score Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-18 17:08:38","doi":"10.21203/rs.3.rs-4519207/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1cce04ba-99bf-4a34-b2aa-b813a52beac3","owner":[],"postedDate":"June 18th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-08-06T14:40:48+00:00","versionOfRecord":[],"versionCreatedAt":"2024-06-18 17:08:38","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4519207","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4519207","identity":"rs-4519207","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}