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      Evaluation of transarterial chemoembolization refractoriness in patients with hepatocellular carcinoma

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          Abstract

          Background & aim

          In clinical practice, transarterial chemoembolization (TACE) has been widely used for the treatment of hepatocellular carcinoma (HCC) beyond as well as within guideline recommendations. Here we aimed to verify whether two consecutive non-responses could be an optimal criterion for creating a rule to stop TACE being performed on these patients.

          Methods

          This study evaluated 200 patients with HCC beyond the Milan criteria, initially treated with TACE. TACE response was determined using the mRECIST criteria via dynamic CT or MRI. Median follow-up duration was 23.9 months.

          Results

          Within the 200 patients analyzed, 183 (91.5%) were male, with a total median age of 59.8 years. The mean size of the largest tumor was 6.8 cm, with 80 (40.0%) patients with ≥4 tumors. After the first TACE procedure, complete response, partial response, stable disease, or progressive disease were observed in 48 (24.0%), 87 (43.5%), 59 (29.5%) and 6 (3.0%) of patients, respectively. 45 (22.5%) patients showed no objective response (OR) following two consecutive TACE sessions. Of these, 28 received a subsequent TACE, with a 10.7% OR rate. Patients without OR showed poorer survival when compared to patients who achieved OR after repeated TACE. Multivariable analysis showed that size of the largest tumor >5cm and high alpha-fetoprotein of >200 ng/mL were significant factors associated with failure of OR to two consecutive TACE sessions.

          Conclusion

          Patients showing no OR to two consecutive TACE sessions will present a poor OR to subsequent TACE procedures. Early transition to systemic therapy may be advocated in such cases.

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          Most cited references15

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          Global patterns of hepatocellular carcinoma management from diagnosis to death: the BRIDGE Study

          Background & Aims Hepatocellular carcinoma (HCC) is the second most common cause of cancer deaths worldwide. The global HCC BRIDGE study was a multiregional, large-scale, longitudinal cohort study undertaken to improve understanding of real-life management of patients with HCC, from diagnosis to death. Methods Data were collected retrospectively from January 2005 to September 2012 by chart reviews of eligible patients newly diagnosed with HCC at participating institutions. Results Forty-two sites in 14 countries contributed final data for 18 031 patients. Asia accounted for 67% of patients, Europe for 20% and North America for 13%. As expected, the most common risk factor was hepatitis C virus in North America, Europe and Japan, and hepatitis B virus in China, South Korea and Taiwan. The most common Barcelona Clinic Liver Cancer stage at diagnosis was C in North America, Europe, China and South Korea, and A in Taiwan and Japan. Across all stages, first HCC treatment was most frequently transarterial chemoembolization in North America, Europe, China and South Korea, percutaneous ethanol injection or radiofrequency ablation in Japan and resection in Taiwan. Survival from first HCC treatment varied significantly by region, with median overall survival not reached for Taiwan and 60, 33, 31, 24 and 23 months for Japan, North America, South Korea, Europe and China respectively (P < 0.0001). Conclusions Initial results from the BRIDGE study confirm previously reported regional trends in patient demographic characteristics and HCC risk factors, document the heterogeneity of treatment approaches across regions/countries and underscore the need for earlier HCC diagnosis worldwide.
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            JSH Consensus-Based Clinical Practice Guidelines for the Management of Hepatocellular Carcinoma: 2014 Update by the Liver Cancer Study Group of Japan

            The Clinical Practice Guidelines for the Management of Hepatocellular Carcinoma proposed by the Japan Society of Hepatology was updated in June 2014 at a consensus meeting of the Liver Cancer Study Group of Japan. Three important items have been updated: the surveillance and diagnostic algorithm, the treatment algorithm, and the definition of transarterial chemoembolization (TACE) failure/refractoriness. The most important update to the diagnostic algorithm is the inclusion of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging as a first line surveillance/diagnostic tool. Another significant update concerns removal of the term “lipiodol” from the definition of TACE failure/refractoriness.
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              Subclassification of BCLC B Stage Hepatocellular Carcinoma and Treatment Strategies: Proposal of Modified Bolondi's Subclassification (Kinki Criteria)

              Intermediate stage hepatocellular carcinoma (HCC) is a very heterogeneous tumor in terms of tumor size (>3 cm ∼ over 10 cm), tumor number (4 ∼ over 20) and liver function (Child-Pugh score 5-9). However, transarterial chemoembolization is the only recommended treatment option according to the Barcelona Clinic Liver Cancer (BCLC) staging. Bolondi's subclassification of BCLC B stage is feasible; however, there are several weak points. Therefore, by modifying Bolondi's subclassification, we have proposed a more simplified subclassification, Kinki criteria. The Kinki criteria consist of 2 factors: liver function (Child-Pugh score 5-7 or 8, 9) and tumor status (Beyond Milan and within up-to-7 criteria; IN and OUT). The Kinki criteria classifies BCLC B stage from B1 (Child-Pugh score 5-7 and within up-to-7), B2 (Child-Pugh score 5-7 and beyond up-to-7) and B3 (Child-Pugh score 8, 9 and any tumor status). These criteria are simple and easy to apply to clinical practice. Therefore, these criteria will stratify the heterogeneous population of BCLC B group patient well and give the treatment indication according to each substage. These criteria should be further validated both retrospectively and prospectively.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: MethodologyRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: InvestigationRole: MethodologyRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                4 March 2020
                2020
                : 15
                : 3
                : e0229696
                Affiliations
                [001]Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
                Cincinnati Children’s Hospital Medical Center, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

                Author information
                http://orcid.org/0000-0002-1544-577X
                http://orcid.org/0000-0002-7631-4124
                Article
                PONE-D-19-28673
                10.1371/journal.pone.0229696
                7055892
                32130270
                72bf84b2-20eb-49da-8350-43553e6d4729
                © 2020 Choi et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 14 October 2019
                : 11 February 2020
                Page count
                Figures: 4, Tables: 2, Pages: 13
                Funding
                Funded by: Bayer HealthCare (DE)
                Award Recipient :
                This study was supported by grants from Bayer. However, Bayer had no role in the study design, data collection, analysis, decision to publish, or preparation of the manuscript. The final decision on content was exclusively retained by the authors.
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