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      Lipiodol as an Imaging Biomarker of Tumor Response After Conventional Transarterial Chemoembolization: Prospective Clinical Validation in Patients with Primary and Secondary Liver Cancer

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          PURPOSE: To prospectively investigate whether Lipiodol can be used as a potential imaging biomarker of tumor response after conventional transarterial chemoembolization (cTACE) for both primary and secondary liver cancer. MATERIALS AND METHODS: This prospective single-center single-arm clinical trial enrolled a total of 39 patients with primary or secondary liver malignancy [hepatocellular carcinoma (HCC), n = 22 and non-HCC, n = 17]. Patients were treated with cTACE according to a standardized protocol and underwent multimodality imaging at baseline [magnetic resonance imaging (MRI)/computed tomography (CT)/positron emission tomography (PET)]; at 24 hours post-TACE (CT); and at 30, 90, and 180 days post-TACE (MRI/CT/PET). Image data analysis included quantitative assessment of tumor characteristics, Lipiodol deposition, fluorodeoxyglucose uptake, and tumor response assessment. Statistical analysis included linear regression, Student's t tests, Wilcoxon rank sum and signed rank test, Chi-square, and Fisher's exact test. RESULTS: Image analysis demonstrated that baseline tumor diameter ( R 2 = 0.4, P = .0001), area ( R 2 = 0.45, P < .0001), volume ( R 2 = 0.3, P < .002), and enhancing volume (cm 3, R 2 = 0.23, P < .002) at baseline correlated inversely with Lipiodol tumor coverage and response rates. Baseline tumor enhancement in % of the total tumor was the only parameter to positively correlate with Lipiodol coverage ( R 2 = 0.189, P = .0456). Patients with high Lipiodol coverage of the tumors showed a higher tumor quantitative European Association for the Study of the Liver response rate at 30-day follow-up ( P = .004). Lipiodol retention in both primary and secondary liver tumors was sustained over time, while nontarget hepatic deposits demonstrated near-complete elimination at 30-day follow-up ( P < .001). CONCLUSION: Lipiodol deposition in liver tumors can be predicted using quantitative baseline imaging characteristics and correlates with tumor response. This supports another role for Lipiodol, namely, that of an imaging biomarker of tumor response after cTACE.

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          Reporting results of cancer treatment.

          On the initiative of the World Health Organization, two meetings on the Standardization of Reporting Results of Cancer Treatment have been held with representatives and members of several organizations. Recommendations have been developed for standardized approaches to the recording of baseline data relating to the patient, the tumor, laboratory and radiologic data, the reporting of treatment, grading of acute and subacute toxicity, reporting of response, recurrence and disease-free interval, and reporting results of therapy. These recommendations, already endorsed by a number of organizations, are proposed for international acceptance and use to make it possible for investigators to compare validly their results with those of others.
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            Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver.

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              Lipiodol transarterial chemoembolization for hepatocellular carcinoma: A systematic review of efficacy and safety data.

              Transarterial chemoembolization (TACE) using lipiodol-based regimens, including the administration of an anticancer-in-oil emulsion followed by embolic agents, is widely used in the treatment of hepatocellular carcinoma (HCC). This approach has been supported by meta-analyses of randomized, controlled trials (RCTs) performed more than a decade ago. We performed a systematic review to understand current efficacy and safety data of lipiodol TACE in treatment of HCC. A search of the literature published between January 1, 1980 and June 30, 2013 was performed using MEDLINE and EMBASE databases. All potentially relevant publications were reviewed and articles were selected based on predefined inclusion and exclusion criteria. Of a total of 1,564 articles reviewed, 101 articles, including a total of 10,108 patients treated with lipiodol TACE, were selected for the efficacy analysis. Objective response rate was 52.5% (95% confidence interval [CI]: 43.6-61.5). Overall survival (OS) was 70.3% at 1 year, 51.8% at 2 years, 40.4% at 3 years, and 32.4% at 5 years. Median OS was 19.4 months (95% CI: 16.2-22.6). A total of 217 articles presenting precise description on numbers of adverse events (AEs) were selected for the safety review: In these studies, a total of 21,461 AEs were reported in 15,351 patients. Liver enzyme abnormalities were the most commonly observed AE, followed by the symptoms associated with postembolization syndrome. Overall mortality rate was 0.6% and the most common cause of death was related to acute liver insufficiency.
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                Author and article information

                Contributors
                Journal
                Transl Oncol
                Transl Oncol
                Translational Oncology
                Neoplasia Press
                1936-5233
                22 February 2020
                March 2020
                22 February 2020
                : 13
                : 3
                : 100742
                Affiliations
                [a ]Department of Radiology and Biomedical Imaging, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06520, USA
                [b ]Institute of Radiology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität, and Berlin Institute of Health, 10117 Berlin, Germany
                [c ]Visage Imaging, Inc., 12625 High Bluff Drive, Suite 205, San Diego, CA 92130, USA
                [d ]PreScience Labs/Cage Pharma, 1812 Ashland Avenue, Baltimore, MD 21205, USA
                [e ]University Medical Center Utrecht, Imaging department, Utrecht, The Netherlands
                [f ]University of California, San Diego, 9500 Gilman Dr, La Jolla, CA 92093
                Author notes
                [* ]Address all correspondence to: Todd Schlachter, Department of Radiology and Biomedical Imaging, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06520, USA. todd.schlachter@ 123456yale.edu
                [1]

                Both authors contributed equally to this work.

                Article
                S1936-5233(19)30434-6 100742
                10.1016/j.tranon.2020.01.003
                7036424
                32092672
                f7c2b4a3-3951-45ae-b026-85c33e08945a
                © 2020 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 18 August 2019
                : 9 January 2020
                : 13 January 2020
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