transcatheter arterial chemoembolization,

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1 Embolization Efficacy and Treatment Effectiveness of Transarterial Therapy for Unresectable Hepatocellular Carcinoma: A Case-Controlled Comparison of Transarterial Ethanol Ablation with Lipiodol Ethanol Mixture versus Transcatheter Arterial Chemoembolization Simon C.H. Yu, MD, FRCR, Joyce W.Y. Hui, FRCR, Edwin P. Hui, FRCP, Frankie Mo, PhD, Paul S.F. Lee, FRCR, John Wong, FRCS, Kit F. Lee, FRCS, Paul B.S. Lai, MD, FRCS, and Winnie Yeo, MD, FRCP PURPOSE: To compare the embolization efficacy and treatment effectiveness of transarterial ethanol ablation (TEA) versus those of chemoembolization and evaluate the correlation between embolization efficacy and treatment effectiveness of these treatments for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A case-controlled study was undertaken with 30 patients in each group matched based on Child-Pugh grade, tumor characteristics, and performance status. Primary endpoints were embolization efficacy (ie, Lipiodol retention within tumor at 2 months) and treatment effectiveness as evaluated by tumor response, disease progression, progression-free survival, and overall survival. The secondary endpoint was correlation between embolization efficacy and treatment effectiveness. RESULTS: Lipiodol retention was greater in the TEA group (89.5% 10.7% vs 47.5% 21.2%; P <.0001). The tumor progression rate at 1 year was higher in the chemoembolization group (five of 30 vs zero of 30; P.0261). One- and 2-year overall survival rates were higher in the TEA group (93.3% and 80.0%, respectively, vs 73.3% and 43.3%, respectively; P.0053). One- and 2-year extrahepatic disease progression rates were lower in the TEA group (P.0002). There were no differences in progression-free survival and intrahepatic disease progression rates at 1 and 2 years. Patients with greater Lipiodol retention (ie, >60%) had better treatment outcomes at 1 year than those with lesser retention, with higher overall survival rates (88.9% vs 66.7%; P.0192), lower intrahepatic disease progression rates (25.6% vs 59.4%; P.0169), lower extrahepatic disease progression rates (0.31% vs 35.5%; P.0047), and higher progression-free survival rates (72.1% vs 36.3%; P.005). CONCLUSIONS: The embolization efficacy and treatment effectiveness of TEA are probably superior to those of chemoembolization for HCC. J Vasc Interv Radiol 2009; 20: Abbreviations: HCC hepatocellular carcinoma, TEA transarterial ethanol ablation From the Departments of Diagnostic Radiology and Organ Imaging (S.C.H.Y., J.W.Y.H., P.S.F.L.), Clinical Oncology (E.P.H., F.M., W.Y.), and Surgery (J.W., K.F.L., P.B.S.L.), Prince of Wales Hospital, the Chinese University of Hong Kong, Ngan Shing Street, Shatin, New Territories, Hong Kong. Received December 18, 2007; final revision received December 3, 2008; accepted December 7, Address correspondence to S.C.H.Y.; simonyu@ cuhk.edu.hk None of the authors have identified a conflict of interest. SIR, 2009 DOI: /j.jvir HEPATOCELLULAR carcinoma (HCC) is one of the most common solid malignancies in the world. There is an increasing incidence of the disease in the United States and other developed Western countries (1,2). In many centers, transcatheter arterial chemoembolization, a common and well recognized transarterial treatment shown to have a significant impact on patient survival 352

2 Volume 20 Number 3 Yu et al 353 Table 1 Patient and Tumor Characteristics and Comparison of Embolization Efficacy between TEA and Chemoembolization Characteristic (3,4), is a mainstay of treatment for patients in whom curative treatment options are not applicable. Other options of transarterial treatment for HCC include bland embolization (5) and radioembolization (6). Transcatheter arterial embolization with a mixture of Lipiodol (Laboratoire Andre Guerbet, Aulnaysous-Bois, France) and ethanol has been shown to be an effective treatment for intrahepatic lesions of HCC, although it is not widely recognized or used (7 9). Transarterial ethanol ablation (TEA) of HCC with use of a Lipiodol ethanol mixture that consists of a decreased proportion of ethanol (33% by volume) represents a treatment concept different from that of transcatheter arterial embolization of HCC with a high proportion of absolute ethanol. Lipiodol ethanol mixtures with reduced ethanol composition have been shown to be associated with a diminished degree of endothelial damage to the arterial feeder vessels of tumor, thereby facilitating effective delivery of Lipiodol ethanol mixture to arterioles such as those in tumor vasculature (10,11). Ethanol produces a longlasting embolization effect by causing endothelial damage and thrombosis of the arteriolar lumen of tumor vasculature, thereby leading to infarction of the tumor. Such Lipiodol ethanol formulations have been found to be safe and effective for the treatment of HCC, especially small lesions in patients with Child-Pugh class A disease (12,13). Because embolization is a vital component in chemoembolization and Lipiodol ethanol treatment, an understanding of embolization efficacy in these TEA (n 30) treatments will allow evaluation of the effectiveness of these treatments. The aims of the present study are to compare the embolization efficacy and treatment effectiveness of TEA with a Lipiodol ethanol mixture versus those of transcatheter arterial chemoembolization for the treatment of patients with unresectable HCC, and to evaluate the correlation between embolization efficacy and treatment effectiveness of these treatments in transarterial treatment of patients with unresectable HCC. MATERIALS AND METHODS Study Design Chemoembolization (n 30) P Value Age (y) SD Sex (M/F) 24/6 23/7.754 Greatest tumor dimension SD (mm) Child-Pugh classification 1.00 A B 2 2 ECOG grade Lipiodol retention 2 months after first treatment (%) Note. ECOG Eastern Cooperative Oncology Group. The present study was a case-controlled study of 60 patients with unresectable HCC treated with transarterial therapy. A group of 30 patients who received Lipiodol ethanol treatment between March and December 2002 was compared with a group of 30 patients who received chemoembolization in Institutional review board approval was obtained for phase I and II studies of Lipiodol ethanol treatment, as well as for the comparative study of Lipiodol ethanol treatment versus chemoembolization. The phase I and II studies of Lipiodol ethanol treatment were commenced in 2002 and completed in late Starting in 2005, patients with HCC were treated with chemoembolization. Thirty consecutive patients who had received Lipiodol ethanol treatment in 2002 and fulfilled the inclusion criteria were selected into the Lipiodol ethanol group. Thirty consecutive patients who had received chemoembolization in 2005 and fulfilled the inclusion criteria were selected into the chemoembolization group. The inclusion criteria for both groups were (i) histologically proven HCC, (ii) Child- Pugh class A/B liver cirrhosis, (iii) solitary tumor with a diameter no greater than 12 cm, and (iv) Eastern Cooperative Oncology Group performance status of 0/1. There were no statistical differences between groups concerning patient age, sex, tumor size, Child-Pugh class, and performance status (Table 1). The primary endpoints of the present study were embolization efficacy and treatment effectiveness. Embolization efficacy was defined as the effectiveness in obliterating tumor vasculature as represented by the degree of Lipiodol retention within the tumor detected 2 months after a single initial treatment. Treatment effectiveness was defined as the effectiveness in achieving a desirable treatment outcome as evaluated by tumor response and patient outcome. The secondary endpoint was correlation between embolization efficacy and treatment effectiveness in terms of patient outcome in the whole group of 60 patients. Parameters of Embolization Efficacy The degree of Lipiodol retention was used as a parameter of embolization efficacy. Lipiodol retention was defined as the ratio of the volume of tumor tissue that was stained with Lipiodol at 2 months after the first treatment to the volume of Lipiodol-stained tumor tissue on the day of the first treatment. Noncontrast computed tomography (CT) of the liver was performed on the day of the first treatment and 2 months after treatment for detection of Lipiodolstained tumor (Figs 1,2). The volume of Lipiodol-stained tumor was acquired from the CT workstation by selecting an intensity threshold of 100 HU. Collection of CT data on the volume of Lipiodol-stained tumor tissue was performed by an independent radiologist. Parameters of Treatment Effectiveness Treatment effectiveness was evaluated based on tumor response and patient outcomes. Tumor response was assessed with triphasic CT in each pa-

3 354 Transarterial Ethanol Ablation vs Chemoembolization for HCC March 2009 JVIR Figure 1. CT images of a solitary 4.8-cm HCC (arrows) treated once with Lipiodol ethanol mixture. (a) CT just after treatment. (b) CT at 2 months after treatment. Figure 2. CT of a solitary 6-cm HCC (arrows) treated once with chemoembolization. (a) CT just after treatment. (b) CT at 2 months after treatment. tient. Tumor response was evaluated with the Response Evaluation Criteria In Solid Tumors (14) based on the 12- month CT or the last CT study before the death of the patient, whichever was earlier. Response of tumor lesions to treatment was classification into four categories: (i) complete response (ie, absence of lesion), (ii) partial response (ie, lesion diameter reduction by 30%), (iii) static disease, and (iv) lesion size progression (ie, lesion diameter increase by 20%). Patient outcome was evaluated based on intrahepatic and extrahepatic disease progression rates at 1 and 2 years, progression-free survival rates at 1 and 2 years, and overall survival rates at 1 and 2 years. Intrahepatic disease progression was defined as the occurrence of any new lesion after the onset of treatment as depicted on a triphasic CT scan. Extrahepatic disease progression was defined by CT evidence of extrahepatic disease, intrahepatic venous invasion, or biliary invasion detected after the onset of treatment. Treatment Procedure The Lipiodol ethanol formulation was prepared by mixing two portions (by volume) of Lipiodol with one portion (by volume) of ethanol to form a clear champagne-like homogenous solution. Transarterial delivery of Lipiodol ethanol mixture into tumor vasculature was performed via catheter-

4 Volume 20 Number 3 Yu et al 355 test. Comparison of lesion size progression was performed by Fisher exact test. Overall survival was defined from the date of first treatment to the date of death or censorship at the date of last follow-up if the patient was still alive. Time to disease progression was defined from the date of first treatment to the date of disease progression or censorship at the date of last follow-up. The log-rank test was used to detect any difference between Lipiodol ethanol and chemoembolization groups at various endpoints. The correlation between treatment outcomes and percentage of Lipiodol retention was compared with the Student t test. All statistical tests were two-sided, and P values less than.05 were considered statistically significant. Figure 3. Radiograph shows catheter position of a typical segmental catheterization and posttreatment intralesional Lipiodol staining in a patient who received Lipiodol ethanol treatment. ization of the tumor feeder vessel(s) with a 5-F catheter or microcatheter. Lipiodol ethanol mixture was infused until there was flow stagnation. An average of 14.5 ml 17.6 of Lipiodol ethanol mixture was given for the first treatment of each patient in the Lipiodol ethanol group. Patients received a median of two treatments (range, 1 5 treatments) throughout the follow-up period. Typically the amount of Lipiodol ethanol mixture given in repeat treatments was much less than that in the initial treatment. Technical details of Lipiodol ethanol treatment were described by Yu et al (15). A standard dose of 20 ml of Lipiodol cisplatin emulsion containing 10 mg of cisplatin was infused through tumor feeder vessel(s) catheterized with a 5-F catheter or microcatheter. Gelatin sponge particle embolization was performed afterward until there was flow stagnation at the feeding hepatic artery. Patients received a median of three treatments (range, 1 6 treatments) throughout the follow-up period. The treatment goal in both groups was delivery of the Lipiodol-based therapeutic agent to fill the tumor vasculature. The goal was achieved typically by lobar or segmental catheterization depending on the size of the lesion (Fig 3). For small focal lesions with an identifiable and sizable feeding vessel, subselective catheterization was sometimes attempted in both groups. A CT scan was obtained after treatment to document tumor coverage with Lipiodol and confirm that the whole tumor has been adequately treated. Additional Lipiodol ethanol treatment or chemoembolization was administered when there was CT evidence of residual or recurrent viable tumor depicted as contrast-enhanced lesions at the arterial phase. All CT reports were prepared by independent radiologists. The decision to perform additional treatment was made by a clinician in conjunction with a radiologist. Statistical Analysis Statistical analysis was performed with SAS software (version 8.2; SAS, Cary, North Carolina). Continuous variables were expressed as means with SDs. Baseline continuous variables were compared by Student t test and categoric variables were compared by 2 RESULTS When comparing Lipiodol ethanol versus chemoembolization, the degree of Lipiodol retention in tumor at 2 months was significantly higher in the Lipiodol ethanol group than in the chemoembolization group (89.5% 10.7% vs 47.5% 21.2%; P.0001; Table 1). Tumor response to treatment at 1 year or less expressed in a ratio of patients showing partial response versus static disease versus lesion size progression were 18/12/0 in the Lipiodol ethanol group and 12/13/5 in the chemoembolization group. When the two groups were compared in terms of proportions of patients with lesion size progression versus nonprogression, the ratios were 0/30 in the Lipiodol ethanol group and 5/25 in the chemoembolization group (P.0261, Fisher exact test; Table 2), indicating a significantly higher incidence of lesion size progression in the chemoembolization group. The 1- and 2-year overall survival rates in the Lipiodol ethanol group (93.3% and 80.0%, respectively) were significantly higher than those in the chemoembolization group (73.3% and 43.3%, respectively; P.0053; Table 2). Extrahepatic disease progression rates in the Lipiodol ethanol group at 1 and 2 years (both 0%) were significantly lower than those in the chemoembolization group (35.5% and 39.2%, respectively; P.0002; Table 2). There was no significant difference in intrahepatic disease progression rates at 1 and 2 years between the Lipiodol eth-

5 356 Transarterial Ethanol Ablation vs Chemoembolization for HCC March 2009 JVIR Table 2 Comparison of Treatment Effectiveness between TEA and Chemoembolization Outcome TEA (n 30) Chemoembolization (n 30) P Value Tumor response*.0261 Nonprogressive lesion Progressive lesion 0 5 Overall survival (%) y y Intrahepatic disease progression (%) y y Extrahepatic disease progression (%) y y Progression-free survival (%) y y * Based on Response Evaluation Criteria In Solid Tumors. Table 3 Correlation at 1 Year Between Embolization Efficacy and Treatment Effectiveness of the Whole Group (N 60) Endpoint at 1 Year Lipiodol Retention (%) 60% 60% P Value HR (95% CI) Survival ( ) Intrahepatic disease progression ( ) Extrahepatic disease progression ( ) Progression-free survival ( ) Note. HR hazard ratio. anol group (30.2% and 41.2%, respectively) and the chemoembolization group (44.3% and 48.0%, respectively; P.2613; Table 2). There was also no significant difference in progressionfree survival rates at 1 and 2 years between the Lipiodol ethanol group (69.8% and 58.8%, respectively) and the chemoembolization group (46% and 42.5%, respectively; P.0588; Table 2). When considering all 60 patients as a whole, it was found that patients with a higher degree of Lipiodol retention in their treated tumors ( 60%) had significantly better clinical outcomes at 1 year than those with a degree of Lipiodol retention of 60% or less in terms of a higher overall survival rate (88.9% vs 66.7%; P.0192), a lower intrahepatic disease progression rate (25.6% vs 59.4%; P.0169), a lower extrahepatic disease progression rate (0.31% vs 35.5%; P.0047), and a higher progression-free survival rate (72.1% vs 36.3%; P.005; Table 3; Fig 4). The overall survival period was prolonged from a mean of 1.28 years 0.13 among patients with no greater than 60% Lipiodol retention to 2.61 years 0.16 among patients with more than 60% Lipiodol retention. Time to intrahepatic disease progression was prolonged from a mean of 0.70 years 0.10 among patients with no greater than 60% Lipiodol retention to 1.41 years 0.10 among patients with more than 60% Lipiodol retention. Progression-free survival period was prolonged from a mean of 0.63 years 0.1 years among patients with no greater than 60% Lipiodol retention to 1.38 years 0.10 among those with more than 60% Lipiodol retention. DISCUSSION The goals of chemoembolization are to deliver a highly concentrated dose of chemotherapy to tumor cells, to prolong the contact time between the chemotherapeutic agents and the tumor cells, and to minimize systemic toxicity from the chemotherapeutic agents (16). Lipiodol is a key ingredient in the treatment protocol of chemoembolization, as it serves the functions of a drug-carrying, tumor-seeking, and embolizing agent. The deliverable chemoembolization agent is prepared in the form of an emulsion by mixing Lipiodol with an equal volume of drug-containing aqueous solution. Embolization of the tumor-feeding arterial branches in the procedure of chemoembolization is achieved partly by the infusion of Lipiodol-containing emulsion and partly by the administration of embolic agents such as gelatin sponge pledgets. As embolization is a vital part of the chemoembolization treatment (17 20), the efficacy of embolization is a crucial factor in treatment effectiveness. The formulation of Lipiodol ethanol mixture with a lowered proportion by volume of Lipiodol (33%) is designed to facilitate thorough infiltration of tumor vasculature by Lipiodol ethanol mixture while maintaining the potency of the embolization power of absolute ethanol in the target vasculature, as it is not diluted by aqueous solution. Theoretically, the preserved embolization potency of a Lipiodol ethanol mixture allows it to embolize portal venules effectively when the Lipiodol ethanol mixture passes to portal venules through the peribiliary plexus (10,11); as a result, effective embolization of portal venules surrounding the tumor blocks off portal blood supply to tumor periphery and prevents the infused agent in the tumor vasculature from draining away through the portal venules (7). If this hypothesis is valid, the embolization efficacy of Lipiodol ethanol mixture is likely to be superior to that of ethanol-free Lipiodol formulations such as those used for chemoembolization. The authors believe TEA has not been used to the extent that chemoembolization is used in the Western world for the following reasons: (i) the promising preliminary results of chemoembolization when it was introduced created an overwhelming favorable response among

6 Volume 20 Number 3 Yu et al 357 Figure 4. Correlation between embolization efficacy and treatment effectiveness of the whole group. (a) Overall survival rate. (b) Freedom from intrahepatic disease progression (c) Freedom from extrahepatic disease progression. (d) Progression-free survival rate. active medical researchers and practitioners in the past decade and a half, so much so that TEA has not gained much attention; (ii) TEA requires a more tedious procedure of subselective catheterization; and (iii) the lack of chemoembolization agents in TEA treatment is less persuasive as an anticancer treatment compared with chemoembolization. The possibility that ischemia and hypoxia may be potent stimulators of angiogenesis and carcinogenesis in the liver (21,22) has created doubts regarding treatments like transarterial embolization for HCC; however, the goal of TEA with Lipiodol ethanol mixture is not to achieve tumor ischemia; rather, it is to completely occlude the vasculature of tumor lesions and thereby achieve infarction of the lesions. Moreover, when the tumor vasculature is infiltrated with Lipiodol ethanol mixture, diffusion of ethanol from tumor vasculature into tumor tissue is likely to occur. It has been shown in several studies (23 27) that percutaneous injection of ethanol into tumor interstitium and chemoembolization may have a synergistic effect that enables effective treatment of large liver tumors (23). Chemoembolization is known to enhance diffusion of ethanol within tumor tissue and achieve complete tumor necrosis (24,25), resulting in significantly prolonged patient survival than that associated with ethanol injection alone (24,27). Given the observation of enhanced treatment effects of combined chemoembolization and ethanol injection, the component of ethanol in Lipiodol ethanol treatment is likely to provide the added advantage of ethanol ablation to the tumor in addition to the treatment effects of transarterial embolization. The formulation of chemoembolization employed in the present study consisted of 10 mg of cisplatin per 20 ml of Lipiodol aqueous emulsion, in which the dosage of chemotherapeutic drug is lower than that commonly used in some countries such as the United States, where the dose of cisplatin used is as high as 150 mg per 20 ml of emulsion. However, the doses of cisplatin used in chemoembolization in some studies that have shown the effectiveness of chemoembolization (4,28) were also as low as 10 mg per 20 ml emulsion. There is no evidence of the requirement of a certain dose threshold of chemotherapeutic drug for effective chemoembolization treatment. The optimal dose of chemo-

7 358 Transarterial Ethanol Ablation vs Chemoembolization for HCC March 2009 JVIR therapeutic drug required for effective chemoembolization treatment is yet to be determined. Effective embolization of arterial tumor feeder vessels and tumor vasculature logically occlude vasculature within the tumor and prevent washout of Lipiodol from the tumor. Therefore, the degree of Lipiodol retention is a reasonable indicator of embolization efficacy. The degree of Lipiodol retention seen on nonenhanced CT has been used for quantitative assessment of the results of embolization in chemoembolization (29). A high degree of Lipiodol retention has been shown to be associated with a significantly prolonged median survival (29) and a greater extent of tumor necrosis resulting from chemoembolization (30). The degree of Lipiodol retention can be assessed mechanically with CT and therefore serves as an objective parameter for comparison between the two treatment groups. The results of the present study show that the embolization efficacy of Lipiodol ethanol treatment in terms of the degree of Lipiodol retention is superior to that of chemoembolization. The treatment effectiveness of Lipiodol ethanol mixture in terms of tumor response and patient outcomes is superior to that of chemoembolization. The results also show that embolization efficacy as represented by the degree of Lipiodol retention is a useful early predictor of the treatment effectiveness of Lipiodol-based transarterial treatments. The 1- and 2-year survival rates of patients treated with the Lipiodol ethanol mixture in our study (93.3% and 80.0%, respectively) are apparently more promising than those of patients treated with transarterial embolization with gelatin sponge fragments in the study of Llovet et al (75% and 50%, respectively) (3). Tumor characteristics in terms of lesion multiplicity and mean lesion size were identical at 52 mm in both studies. The 1- and 2-year survival rates associated with chemoembolization in our study (73.3% and 43.3%, respectively) compared favorably with those in the study of Lo et al (57% and 31.4%, respectively) (4), although they were slightly less favorable than those of Llovet et al (3). The occurrence of new intrahepatic tumors is relatively independent of the result of treatment of existing tumors, but it is an indicator of the underlying liver condition. Molecular studies have shown that recurrence after resection has two components. The main component, which occurs mainly within the first 2 years after resection (31), represents true metastasis that results from HCC dissemination before resection and is undetectable by imaging techniques (32). The other component includes metachronous tumors arising de novo in a preneoplastic cirrhotic liver (33). The parameter of intrahepatic disease progression used in our study is an indicator of occurrence of new intrahepatic lesions. The fact that there was no difference in intrahepatic disease progression rate between the Lipiodol ethanol group and the chemoembolization group indicated that there was no difference in the patients underlying liver condition between groups. The occurrence of extrahepatic disease reflects a failure of control of intrahepatic lesions that subsequently invade extrahepatic structures; it is therefore an indicator of treatment effect to the intrahepatic tumor. The fact that there was a significantly higher rate of extrahepatic disease progression in the chemoembolization group indicated that treatment effectiveness of chemoembolization is inferior to that of the Lipiodol ethanol mixture. Further analysis of our study result by correlating the degree of Lipiodol retention to treatment effectiveness from the perspective of the whole group of 60 patients provided a cross-check of the results of the comparison between the two subgroups. The results of such further analysis confirmed the correlation between the degree of Lipiodol retention and treatment effectiveness. It was consistent with the results of comparison between the two subgroups, in that the degree of Lipiodol retention was higher in the Lipiodol ethanol group, as was the treatment effectiveness. No correlation between Lipiodol retention and treatment effectiveness within each subgroup was carried out because the numbers of subjects in the subgroups were not sufficient and the variation of the degree of Lipiodol retention within the Lipiodol ethanol group was too small. Potential toxicities to normal liver may include ischemic damage to normal hepatocytes leading to atrophy of liver parenchyma. However, with selective catheterization to avoid excessive delivery of Lipiodol ethanol mixture to normal liver, complications of transarterial treatment such as acute hepatic decompensation and irreversible hepatic decompensation (8.6% and 0.6%, respectively [15]) have been reported to occur much less frequently with Lipiodol ethanol treatment compared with chemoembolization (20% and 3%, respectively [34]). Other known complications of chemoembolization such as gastrointestinal bleeding from peptic ulcer or gastritis, hepatic encephalopathy, variceal bleeding, liver abscess, acalculous cholecystitis, and liver abscess did not occur with Lipiodol ethanol treatment in our study or in a previous study (31). A limitation of the present study was that it was not a randomized control trial. The number of patients recruited was modest. The duration of follow-up was not prolonged. Nevertheless, the number of patients recruited was sufficient to show a significant difference in embolization efficacy and treatment effectiveness between the two groups. The duration of follow-up was adequate for observation of 1- and 2-year survival rates, and was conclusive in showing a significant difference in clinical outcome in favor of the Lipiodol ethanol group, such that a longer duration of follow-up was not necessary. Although the current study was not a randomized controlled trial, it provides solid evidence to justify further study in the form of randomized controlled trials on a larger scale. In conclusion, our findings suggest that embolization efficacy and treatment effectiveness of TEA with Lipiodol ethanol mixture is probably superior to that of chemoembolization for the treatment of patients with unresectable HCC. Embolization efficacy as represented by the degree of Lipiodol retention is a useful early predictor of treatment effectiveness. 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