Quality Improvement Guidelines for Transhepatic Arterial Chemoembolization, Embolization, and Chemotherapeutic Infusion for Hepatic Malignancy

Abstract

PreambleThe membership of the Society of Interventional Radiology (SIR) Standards of Practice Committee represents experts in a broad spectrum of interventional procedures from the private and academic sectors of medicine. Generally, Standards of Practice Committee members dedicate the vast majority of their professional time to performing interventional procedures; as such, they represent a valid broad expert constituency of the subject matter under consideration for standards production.Technical documents specifying the exact consensus and literature review methodologies, as well as the institutional affiliations and professional credentials of the authors of this document, are available upon request from SIR, 3975 Fair Ridge Dr., Suite 400 N., Fairfax, VA 22033.MethodologySIR produces its Standards of Practice documents using the following process. Standards documents of relevance and timeliness are conceptualized by the Standards of Practice Committee members. A recognized expert is identified to serve as the principal author for the standard. Additional authors may be assigned depending on the magnitude of the project.An in-depth literature search is performed with use of electronic medical literature databases. Then, a critical review of peer-reviewed articles is performed with regard to the study methodology, results, and conclusions. The qualitative weight of these articles is assembled into an evidence table, which is used to write the document such that it contains evidence-based data with respect to content, rates, and thresholds.When the evidence of literature is weak, conflicting, or contradictory, consensus for the parameter is reached by a minimum of 12 Standards of Practice Committee members by using a modified Delphi Consensus Method (Appendix A). For the purposes of these documents, consensus is defined as 80% Delphi participant agreement on a value or parameter.The draft document is critically reviewed by the Standards of Practice Committee members by telephone conference calling or face-to-face meeting. The finalized draft from the Committee is sent to the SIR membership for further input/criticism during a 30-day comment period. These comments are discussed by the Standards of Practice Committee, and appropriate revisions made to create the finished standards document. Before its publication, the document is endorsed by the SIR Executive Council.IntroductionIntraarterial therapy for a variety of hepatic malignancies represents an important therapeutic procedure in individuals with liver-dominant neoplasms. Such tumors include primary hepatic malignancies and certain other cancers in which the liver is the dominant site of disease. A variety of different cancers are amenable to treatment (1Lo C.M. Ngan H. Tso W.K. et al.Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma.Hepatology. 2002; 35: 1164-1171Crossref PubMed Scopus (2164) Google Scholar, 2Llovet J.M. Real M.I. Montana X. et al.Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial.Lancet. 2002; 359: 1734-1739Abstract Full Text Full Text PDF PubMed Scopus (2831) Google Scholar, 3Gupta S. Yao J.C. Ahrar K. et al.Hepatic artery embolization and chemoembolization for treatment of patients with metastatic carcinoid tumors: the M.D. Anderson experience.Cancer J. 2003; 9: 261-267Crossref PubMed Scopus (169) Google Scholar, 4Salman H.S. Cynamon J. Jagust M. et al.Randomized phase II trial of embolization therapy versus chemoembolization therapy in previously treated patients with colorectal carcinoma metastatic to the liver.Clin Colorectal Cancer. 2002; 2: 173-179Abstract Full Text PDF PubMed Scopus (47) Google Scholar). Success with chemoembolization and embolization has been reported with the majority of reports focusing on chemoembolization. Nearly 500,000 patients worldwide are diagnosed with hepatocellular carcinoma (HCC) annually, and the incidence in the United States is increasing dramatically (5Velazquez R.F. Rodriguez M. Navascues C.A. et al.Prospective analysis of risk factors for hepatocellular carcinoma in patients with liver cirrhosis.Hepatology. 2003; 37: 520-527Crossref PubMed Scopus (369) Google Scholar, 6Caturelli E. Siena D.A. Fusilli S. et al.Transcatheter arterial chemoembolization for hepatocellular carcinoma in patients with cirrhosis: evaluation of damage to nontumorous liver tissue—long-term prospective study.Radiology. 2000; 215: 123-128Crossref PubMed Scopus (101) Google Scholar). Most patients with HCC are not surgical candidates at the time of referral to interventional radiology. External-beam radiation therapy is ineffective, and stereotactic radiation therapy remains experimental, with fewer cumulative data than chemoembolization (7Cardenes H.R. Price T.R. Perkins S.M. et al.Phase I feasibility trial of stereotactic body radiation therapy for primary hepatocellular carcinoma.Clin Transl Oncol. 2010; 12: 218-225Crossref PubMed Scopus (221) Google Scholar). Targeted therapies such as sorafenib (Nexavar), although statistically superior to supportive care, have shown limited effectiveness in the treatment of HCC (8Llovet J.M. Ricci S. Mazzaferro V. et al.Sorafenib in advanced hepatocellular carcinoma.N Engl J Med. 2008; 359: 378-390Crossref PubMed Scopus (8740) Google Scholar). Systemic regimens remain ineffective at prolonging survival (9Kanematsu T. Furui J. Yanaga K. Okudaira S. Shimada M. Shirabe K. A 16-year experience in performing hepatic resection in 303 patients with hepatocellular carcinoma: 1985-2000.Surgery. 2002; 131: S153-S158Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar). Transplantation remains the best curative option for HCC. The demand for donated organs continues to outstrip supply (10Wiesner R. Edwards E. Freeman R. et al.Model for end-stage liver disease (MELD) and allocation of donor livers.Gastroenterology. 2003; 124: 91-96Abstract Full Text Full Text PDF PubMed Scopus (1935) Google Scholar). Many patients require some kind of image-guided therapy as a bridge to transplantation or as palliative therapy (11Fisher R.A. Maluf D. Cotterell A.H. et al.Non-resective ablation therapy for hepatocellular carcinoma: effectiveness measured by intention-to-treat and dropout from liver transplant waiting list.Clin Transplant. 2004; 18: 502-512Crossref PubMed Scopus (88) Google Scholar).The liver is the dominant site of metastatic disease for a number of malignancies, including colorectal carcinoma, neuroendocrine tumors, and metastatic uveal melanoma. Fewer than 20% of patients with metastatic colorectal carcinoma are candidates for curative surgical resection (12Nordlinger B. Vaillant J.C. Guiguet M. et al.Survival benefit of repeat liver resections for recurrent colorectal metastases: 143 cases Association Francaise de Chirurgie.J Clin Oncol. 1994; 12: 1491-1496PubMed Google Scholar). Advances in systemic and biologic therapies have provided significant improvement in survival with colorectal metastases, but these therapies have limited benefit for the majority of patients with metastatic neuroendocrine tumors (13Hurwitz H. Fehrenbacher L. Novotny W. et al.Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer.N Engl J Med. 2004; 350: 2335-2342Crossref PubMed Scopus (9091) Google Scholar, 14Oberg K. Chemotherapy and biotherapy in neuroendocrine tumors.Curr Opin Oncol. 1993; 5: 110-120PubMed Google Scholar, 15Ridolfi R. Amaducci L. Derni S. Fabbri L. Innocenti M.P. Vignutelli P. Chemotherapy with 5-fluorouracil and streptozotocin in carcinoid tumors of gastrointestinal origin: experiences with 13 patients.J Chemother. 1991; 3: 328-331PubMed Google Scholar, 16Delaunoit T. Van den Eynde M. Borbath I. et al.Role of chemotherapy in gastro-entero-pancreatic neuroendocrine tumors: the end of a story?.Acta Gastroenterol Belg. 2009; 72: 49-53PubMed Google Scholar). Nonsurgical candidates often have diffuse disease. Chemoembolization, and embolization (for neuroendocrine tumors), can play an important role in the treatment of these patients, particularly when primary systemic regimens have failed.These guidelines are written to be used in quality improvement programs to assess chemoembolization. The most important processes of care are (i) patient selection, (ii) performing the procedure, and (iii) monitoring the patient. The outcome measures or indicators for these processes are indications, success rates, and complication rates. Outcome measures are assigned threshold levels.DefinitionsChemoembolization refers to treatment with a mixture of chemotherapy and embolic agents, typically as oily chemoembolization or drug-eluting bead chemoembolization. •Oily chemoembolization is defined as the infusion of a mixture of chemotherapeutic agents with ethiodized oil (Ethiodol; Guerbet, Villepinte, France) followed by embolization with particles such as calibrated microspheres, polyvinyl alcohol, or Gelfoam (absorbable gelatin sponge).•Drug-eluting bead chemoembolization is defined as the infusion of calibrated microspheres that are designed to bond with chemotherapeutic agents and release the drugs over time following treatment.•Embolization is defined as blockade of hepatic arterial flow with particles alone (typically calibrated microspheres, polyvinyl alcohol, or Gelfoam).•Immunoembolization refers to infusion of granulocyte macrophage-colony stimulating factor with Ethiodol and Gelfoam.•Hepatic artery chemotherapeutic infusion is defined as injection of chemotherapy with or without ethiodized oil in the hepatic artery without embolization.•Liver-dominant neoplasm is defined as a malignancy in which the hepatic component is the only site of disease or is the site of disease most likely to lead to patient morbidity and/or mortality.•Image-guided therapy refers to the use of fluoroscopy, digital subtraction angiography, C-arm computed tomography (CT), CT, ultrasound (US), or magnetic resonance (MR) imaging to target and monitor treatment of tumors for therapy. In the liver, this is accomplished by catheter-based means (as outlined earlier) or by percutaneous tumor ablation (17Goldberg S.N. Charboneau J.W. Dodd III, G.D. et al.Image-guided tumor ablation: proposal for standardization of terms and reporting criteria.Radiology. 2003; 228: 335-345Crossref PubMed Scopus (344) Google Scholar).•Tumor ablation is defined as the direct application of chemical or thermal therapies to a specific focal tumor (or tumors) in an attempt to achieve eradication or substantial tumor destruction. Tumor ablation methods fall into one of three main categories: chemical, thermal, or biomechanical (17Goldberg S.N. Charboneau J.W. Dodd III, G.D. et al.Image-guided tumor ablation: proposal for standardization of terms and reporting criteria.Radiology. 2003; 228: 335-345Crossref PubMed Scopus (344) Google Scholar).•Chemical ablation refers to instillation of a pharmacologic agent to cause tumor necrosis. Examples of chemical agents include absolute ethanol and acetic acid.•Thermal ablation refers to application of energy to cause tumor necrosis. Examples of energy sources include radiofrequency, laser, microwave, US, and cryotherapy.•Biomechanical ablation refers to application of energy to lead to cell breakdown. The primary example is irreversible electroporation.Chemoembolization, embolization, and chemotherapeutic infusion are performed after catheterization of the proper, lobar, segmental, or subsegmental hepatic arteries by using standard angiographic principles as described in the SIR quality improvement guidelines for diagnostic angiography (18Singh H. Cardella J.F. Cole P.E. et al.Quality improvement guidelines for diagnostic arteriography.J Vasc Interv Radiol. 2003; 14: 283S-288SPubMed Scopus (54) Google Scholar). Unless otherwise stated, references in this document will specifically refer to oily chemoembolization, as the majority of the existing literature has used this technique.Although practicing physicians should strive to achieve perfect outcomes (eg, 100% success, 0% complications), in practice all physicians will fall short of this ideal to a variable extent. Thus indicator thresholds may be used to assess the efficacy of ongoing quality improvement programs. For the purposes of these guidelines, a threshold is a specific level of an indicator which should prompt a review. “Procedure thresholds” or “overall thresholds” reference a group of indicators for a procedure, eg, major complications. Individual complications may also be associated with complication-specific thresholds. When measures such as indications or success rates fall below a (minimum) threshold, or when complication rates exceed a (maximum) threshold, a review should be performed to determine causes and to implement changes, if necessary. For example, if the incidence of abscess formation is one measure of the quality of chemoembolization, values in excess of the defined threshold (in this case, 2%) should trigger a review of policies and procedures within the department to determine the causes and to implement changes to lower the incidence of the complication. Thresholds may vary from those listed here; for example, patient referral patterns and selection factors may dictate a different threshold value for a particular indicator at a particular institution. Therefore, setting universal thresholds is very difficult, and each department is urged to alter the thresholds as needed to higher or lower values to meet its own quality improvement program needs.Complication stratification in interventional radiology is currently undergoing revision, but, to date, has been performed on the basis of procedural outcomes. Major complications result in admission to a hospital for therapy (for outpatient procedures), an unplanned increase in the level of care, prolonged hospitalization, permanent adverse sequelae, or death. Minor complications result in no sequelae; they may require nominal therapy or a short hospital stay for observation (generally overnight; Appendix B). The complication rates and thresholds listed herein refer to major complications.IndicationsGeneral IndicationsChemoembolization is indicated in patients with liver-dominant hepatic malignancies who are not candidates for curative resection. All patients should undergo preprocedural imaging evaluation including some combination of contrast-enhanced CT, MR imaging, and/or positron emission tomography/CT to ensure that disease is liver-dominant. Although limited treatment is possible in the setting of portal vein thrombosis, outcomes are optimized in the setting of a patent portal vein or with hepatopetal flow via collateral vessels (19Pentecost M.J. Daniels J.R. Teitelbaum G.P. Stanley P. Hepatic chemoembolization: safety with portal vein thrombosis.J Vasc Interv Radiol. 1993; 4: 347-351Abstract Full Text PDF PubMed Scopus (75) Google Scholar, 20Chung J. Park J. Han J. Choi B. Han M. Hepatocellular carcinoma and portal vein invasion: results of treatment with transcatheter oily chemoembolization.AJR Am J Roentgenol. 1995; 165: 315-321Crossref PubMed Scopus (127) Google Scholar, 21Georgiades C.S. Hong K. D'Angelo M. Geschwind J.F. Safety and efficacy of transarterial chemoembolization in patients with unresectable hepatocellular carcinoma and portal vein thrombosis.J Vasc Interv Radiol. 2005; 16: 1653-1659Abstract Full Text Full Text PDF PubMed Scopus (198) Google Scholar). If there is a question of adequate portal perfusion at cross-sectional imaging, confirmation can be obtained at catheter angiography immediately preceding chemoembolization. Patient performance status should be determined during the preliminary interventional radiology clinic visit. Preprocedural evaluation also includes laboratory evaluation including complete blood count, prothrombin time, and evaluation of liver and kidney function. Exclusion criteria based on laboratory values are not definitively established. However, the constellation of more than 50% liver replacement with tumor, bilirubin level greater than 2 mg/dL, lactate dehydrogenase level greater than 425 mg/dL, and aspartate aminotransferase level greater than 100 IU/L has a strong anecdotal association with increased postprocedural mortality (22Berger D.H. Carrasco C.H. Hohn D.C. Curley S.A. Hepatic artery chemoembolization or embolization for primary and metastatic liver tumors: post-treatment management and complications.J Surg Oncol. 1995; 60: 116-121Crossref PubMed Scopus (70) Google Scholar). Individual abnormalities of these four parameters have not been shown to predict adverse outcome from chemoembolization (23Brown D.B. Fundakowski C.E. Lisker-Melman M. et al.Comparison of MELD and Child-Pugh scores to predict survival after chemoembolization for hepatocellular carcinoma.J Vasc Interv Radiol. 2004; 15: 1209-1218Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar). Laboratory values and scoring systems have been used differently by other authors. Commonly used scoring systems are outlined in Table 1, Table 2, Table 3. A bilirubin cutoff value of 3 mg/dL has been described (24Stuart K. Stokes K. Jenkins R. Trey C. Clouse M. Treatment of hepatocellular carcinoma using doxorubicin/ethiodized oil/gelatin powder chemoembolization.Cancer. 1993; 72: 3202-3209Crossref PubMed Scopus (86) Google Scholar). The Child-Pugh scoring system is superior to the Model for End-stage Liver Disease system at predicting long-term survival in HCC (23Brown D.B. Fundakowski C.E. Lisker-Melman M. et al.Comparison of MELD and Child-Pugh scores to predict survival after chemoembolization for hepatocellular carcinoma.J Vasc Interv Radiol. 2004; 15: 1209-1218Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar). Patients with Child-Pugh class A disease or class B disease with an albumin level of at least 3.4 g/dL have improved survival. Another group (25Testa R. Testa E. Giannini E. et al.Trans-catheter arterial chemoembolisation for hepatocellular carcinoma in patients with viral cirrhosis: role of combined staging systems, Cancer Liver Italian Program (CLIP) and Model for End-stage Liver Disease (MELD), in predicting outcome after treatment.Aliment Pharmacol Ther. 2003; 17: 1563-1569Crossref PubMed Scopus (51) Google Scholar) found that Model for End-stage Liver Disease scores greater than 10 and Cancer of the Liver Italian Program scores greater than 2 were negative predictors of survival. The optimal scoring system to predict survival following therapy remains undefined, and investigation of novel predictors of outcome continues (26Hu H.T. Kim J.H. Lee L.S. et al.Chemoembolization for hepatocellular carcinoma: multivariate analysis of predicting factors for tumor response and survival in a 362-patient cohort.J Vasc Interv Radiol. 2011; 22: 917-923Abstract Full Text Full Text PDF PubMed Scopus (84) Google Scholar, 27Huang Z.L. Luo J. Chen M.S. Li J.Q. Shi M. Blood neutrophil-to-lymphocyte ratio predicts survival in patients with unresectable hepatocellular carcinoma undergoing transarterial chemoembolization.J Vasc Interv Radiol. 2011; 22: 702-709Abstract Full Text Full Text PDF PubMed Scopus (90) Google Scholar, 28Shim J.H. Park J.W. Choi J.I. Kim H.B. Lee W.J. Kim C.M. Does postembolization fever after chemoembolization have prognostic significance for survival in patients with unresectable hepatocellular carcinoma?.J Vasc Interv Radiol. 2009; 20: 209-216Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar).Table 1Child-Pugh Scoring SystemVariable123EncephalopathyNoneModerateSevereAscitesNoneModerateSevereBilirubin (mg/dL)< 22–3> 3Albumin (g/dL)> 3.52.8–3.4< 2.8Prothrombin time (s)< 1415–17> 18Note.—A score of 5–6 represents Child-Pugh class A disease, 7–9 represents class B disease, and 10–15 represents class C disease. Open table in a new tab Table 2Model for End-Stage Liver Disease Scoring SystemR = 0.957 × loge (creatinine [mg/dL)] + 0.378 × loge (bilirubin [mg/dL]) + 1.12 × loge (INR) + 0.643 × (cause of cirrhosis [0 for alcohol-induced cirrhosis, 1 for non–alcohol-induced cirrhosis])Note.—INR = International Normalized Ratio. Open table in a new tab Table 3Cancer of the Liver Italian Program Scoring SystemVariable0 Points1 Point2 PointsChild-Pugh classABCTumor morphologyUninodularMultinodularMassive/> 50% of liverα-Fetoprotein (ng/mL)< 400> 400NAMacrovascular invasionNoYesYesNote.—NA = not applicable. Open table in a new tab Hepatocellular CarcinomaSecondary to underlying cirrhosis, fewer than 20% of patients are candidates for surgical resection (9Kanematsu T. Furui J. Yanaga K. Okudaira S. Shimada M. Shirabe K. A 16-year experience in performing hepatic resection in 303 patients with hepatocellular carcinoma: 1985-2000.Surgery. 2002; 131: S153-S158Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar). Transplantation remains the only curative option for patients with HCC, and individuals with limited disease (ie, one tumor < 5 cm or three tumors < 3 cm each) should be evaluated for transplantation during workup as part of a multidisciplinary effort. In potential transplant recipients, chemoembolization may decrease the drop-off rate from the transplant list and limit recurrence when a new organ has been obtained (29Frangakis C. Geschwind J.F. Kim D. et al.Chemoembolization decreases drop-off risk of hepatocellular carcinoma patients on the liver transplant list.Cardiovasc Intervent Radiol. 2011; 34: 1254-1261Crossref PubMed Scopus (21) Google Scholar, 30Bharat A. Brown D.B. Crippin J.S. et al.Pre-liver transplantation locoregional adjuvant therapy for hepatocellular carcinoma as a strategy to improve longterm survival.J Am Coll Surg. 2006; 203: 411-420Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar). Chemoembolization is being investigated for intrahepatic recurrence following transplantation as well (31Zhou B. Shan H. Zhu K.S. et al.Chemoembolization with lobaplatin mixed with iodized oil for unresectable recurrent hepatocellular carcinoma after orthotopic liver transplantation.J Vasc Interv Radiol. 2010; 21: 333-338Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar). In limited experience, chemoembolization has been found to be effective in management of larger tumors and as adjuvant therapy for HCC resection (32Liu Y. Yang R. Preoperative combined with postoperative chemoembolization can improve survival in patients with hepatocellular carcinoma: a single-center study.J Vasc Interv Radiol. 2009; 20: 472-483Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar, 33Miyayama S. Yamashiro M. Okuda M. et al.Chemoembolization for the treatment of large hepatocellular carcinoma.J Vasc Interv Radiol. 2010; 21: 1226-1234Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar).Initial randomized trials evaluating chemoembolization versus symptomatic treatment had disappointing results (34Bruix J. Castells A. Montanya X. et al.Phase II study of transarterial embolization in European patients with hepatocellular carcinoma: need for controlled trials.Hepatology. 1994; 20: 643-650Crossref PubMed Scopus (88) Google Scholar, 35Bruix J. Llovet J.M. Castells A. et al.Transarterial embolization versus symptomatic treatment in patients with advanced hepatocellular carcinoma: results of a randomized, controlled trial in a single institution.Hepatology. 1998; 27: 1578-1583Crossref PubMed Scopus (508) Google Scholar, 36Pelletier G. Roche A. Ink O. et al.A randomized trial of hepatic arterial chemoembolization in patients with unresectable hepatocellular carcinoma.J Hepatol. 1990; 11: 181-184Abstract Full Text PDF PubMed Scopus (388) Google Scholar, 37Pelletier G. Ducreux M. Gay F. et al.Treatment of unresectable hepatocellular carcinoma with lipiodol chemoembolization: a multicenter randomized trial Groupe CHC.J Hepatol. 1998; 29: 129-134Abstract Full Text PDF PubMed Scopus (389) Google Scholar). However, three well constructed randomized trials (1Lo C.M. Ngan H. Tso W.K. et al.Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma.Hepatology. 2002; 35: 1164-1171Crossref PubMed Scopus (2164) Google Scholar, 2Llovet J.M. Real M.I. Montana X. et al.Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial.Lancet. 2002; 359: 1734-1739Abstract Full Text Full Text PDF PubMed Scopus (2831) Google Scholar, 38Barone M. Ettorre G.C. Ladisa R. et al.Transcatheter arterial chemoembolization (TACE) in treatment of hepatocellular carcinoma.Hepatogastroenterology. 2003; 50: 183-187PubMed Google Scholar) have demonstrated significantly improved survival with chemoembolization. Poor outcomes from the initial trials can be directly linked to treatment of patients with advanced disease and to administration of excessive therapy (39Ray Jr, C.E. Haskal Z.J. Geschwind J.F. Funaki B.S. The use of transarterial chemoembolization in the treatment of unresectable hepatocellular carcinoma: a response to the Cochrane Collaboration Review of 2011.J Vasc Interv Radiol. 2011; 22: 1693-1696Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar). These outcomes reinforce the need to treat patients with well compensated cirrhosis and to repeat therapy in the setting of viable tumor on follow-up cross-sectional imaging (40Ernst O. Sergent G. Mizrahi D. Delemazure O. Paris J. L'Hermine C. Treatment of hepatocellular carcinoma by transcatheter arterial chemoembolization: comparison of planned periodic chemoembolization and chemoembolization based on tumor response.AJR Am J Roentgenol. 1999; 172: 59-64Crossref PubMed Scopus (110) Google Scholar). Many patients whose disease is treatable with chemoembolization may also be treatable with yttrium-90 as well (41Lance C. McLennan G. Obuchowski N. et al.Comparative analysis of the safety and efficacy of transcatheter arterial chemoembolization and yttrium-90 radioembolization in patients with unresectable hepatocellular carcinoma.J Vasc Interv Radiol. 2011; 22: 1697-1705Abstract Full Text Full Text PDF PubMed Scopus (81) Google Scholar). Patients with small tumors may also be considered for percutaneous ablative therapies, alone or in combination with chemoembolization (42Rossi S. Garbagnati F. Lencioni R. et al.Percutaneous radio-frequency thermal ablation of nonresectable hepatocellular carcinoma after occlusion of tumor blood supply.Radiology. 2000; 217: 119-126Crossref PubMed Scopus (454) Google Scholar, 43Yamakado K. Nakatsuka A. Ohmori S. et al.Radiofrequency ablation combined with chemoembolization in hepatocellular carcinoma: treatment response based on tumor size and morphology.J Vasc Interv Radiol. 2002; 13: 1225-1232Abstract Full Text Full Text PDF PubMed Scopus (183) Google Scholar, 44Li Y.H. Wang C.S. Liao L.Y. et al.Long-term survival of Taiwanese patients with hepatocellular carcinoma after combination therapy with transcatheter arterial chemoembolization and percutaneous ethanol injection.J Formos Med Assoc. 2003; 102: 141-146PubMed Google Scholar). The choice between therapies should be based on the overall size, number, and location of the tumors.Embolization for HCC has been demonstrated to be effective (45Brown K.T. Nevins A.B. Getrajdman G.I. et al.Particle embolization for hepatocellular carcinoma.J Vasc Interv Radiol. 1998; 9: 822-828Abstract Full Text PDF PubMed Scopus (83) Google Scholar, 46Maluccio M.A. Covey A.M. Porat L.B. et al.Transcatheter arterial embolization with only particles for the treatment of unresectable hepatocellular carcinoma.J Vasc Interv Radiol. 2008; 19: 862-869Abstract Full Text Full Text PDF PubMed Scopus (144) Google Scholar). Trials of drug-eluting beads loaded with doxorubicin and other agents are emerging (47Lammer J. Malagari K. Vogl T. et al.Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study.Cardiovasc Intervent Radiol. 2010; 33: 41-52Crossref PubMed Scopus (1140) Google Scholar, 48Malagari 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: 541-551Crossref PubMed Scopus (285) Google Scholar, 49Malagari K. Pomoni M. Spyridopoulos T.N. et al.Safety profile of sequential transcatheter chemoembolization with DC Bead: results of 237 hepatocellular carcinoma (HCC) patients.Cardiovasc Intervent Radiol. 2011; 34: 774-785Crossref PubMed Scopus (106) Google Scholar, 50Nicolini A. Martinetti L. Crespi S. Maggioni M. Sangiovanni A. Transarterial chemoembolization with epirubicin-eluting beads versus transarterial embolization before liver transplantation for hepatocellular carcinoma.J Vasc Interv Radiol. 2010; 21: 327-332Abstract Full Text Full Text PDF PubMed Scopus (105) Google Scholar). In a prospective, multicenter, randomized trial with a primary endpoint of tumor response at 6 months from treatment (47Lammer J. Malagari K. Vogl T. et al.Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study.Cardiovasc Intervent Radiol. 2010; 33: 41-52Crossref PubMed Scopus (1140) Google Scholar), there was not a statistical difference between drug-eluting beads and oily chemoembolization. However, patients with limited hepatic reserve or performance status showed better outcomes with drug-eluting beads compared with chemoembolization. In a single-center pro