{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T17:48:54Z","timestamp":1789408134052,"version":"build-2803163510"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2022,5,26]],"date-time":"2022-05-26T00:00:00Z","timestamp":1653523200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,5,26]],"date-time":"2022-05-26T00:00:00Z","timestamp":1653523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100016036","name":"Health~Holland","doi-asserted-by":"crossref","award":["40-41200-98-9286"],"award-info":[{"award-number":["40-41200-98-9286"]}],"id":[{"id":"10.13039\/100016036","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cardiovasc Intervent Radiol"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>To investigate the biodistribution of holmium-166 microspheres (<jats:sup>166<\/jats:sup>Ho-MS) when administered after radiofrequency ablation (RFA) of early-stage hepatocellular carcinoma (HCC). The aim is to establish a perfused liver administration dose that results in a tumoricidal dose of holmium-166 on the hyperaemic zone around the ablation necrosis (i.e. target volume).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Materials and Methods<\/jats:title>\n                <jats:p>This is a multicentre, prospective, dose-escalation study in HCC patients with a solitary lesion 2\u20135\u00a0cm, or a maximum of 3 lesions of\u2009\u2264\u20093\u00a0cm each. The day after RFA patients undergo angiography and cone-beam CT (CBCT) with (super)selective infusion of technetium-99\u00a0m labelled microalbumin aggregates (<jats:sup>99m<\/jats:sup>Tc-MAA). The perfused liver volume is segmented from the CBCT and <jats:sup>166<\/jats:sup>Ho-MS is administered to this treatment volume 5\u201310\u00a0days later. The dose of holmium-166 is escalated in a maximum of 3 patient cohorts (60\u00a0Gy, 90\u00a0Gy and 120\u00a0Gy) until the endpoint is reached. SPECT\/CT is used to determine the biodistribution of holmium-166. The endpoint is met when a dose of\u2009\u2265\u2009120\u00a0Gy has been reached on the target volume in 9\/10 patients of a cohort. Secondary endpoints include toxicity, local recurrence, disease-free and overall survival.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Discussion<\/jats:title>\n                <jats:p>This study aims to find the optimal administration dose of adjuvant radioembolization with <jats:sup>166<\/jats:sup>Ho-MS after RFA. Ultimately, the goal is to bring the efficacy of thermal ablation up to par with surgical resection for early-stage HCC patients.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>Clinicaltrials.gov identifier: NCT03437382.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00270-022-03162-7","type":"journal-article","created":{"date-parts":[[2022,5,26]],"date-time":"2022-05-26T21:02:41Z","timestamp":1653598961000},"page":"1057-1063","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Study Protocol: Adjuvant Holmium-166 Radioembolization After Radiofrequency Ablation in Early-Stage Hepatocellular Carcinoma Patients\u2014A Dose-Finding Study (HORA EST HCC Trial)"],"prefix":"10.1007","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4992-9967","authenticated-orcid":false,"given":"Pim","family":"Hendriks","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daphne D. 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Burgmans has received an educational grant from Boston Scientific. None are related to the current project. J.F.W. Nijsen is co-founder and part time scientific director of Quirem Medical which has been acquired by Terumo Europe NV in July 2020. Nijsen is entitled to certain milestone payments from Terumo which are related to Quirem\u2019s financial, operational and regulatory performance in the future. Furthermore, Nijsen is inventor on the patents related to radioactive microspheres that are assigned to University Medical Center Utrecht Holding BV, Quirem Medical or BASF Corp. The activities of J.F.W. Nijsen within Quirem Medical are approved and supported by the Board of Directors of the Radboudumc. All other authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"For this type of study, consent for publication is not required.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and\/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Approval of this study was provided by the Committee of Medical Ethics of the Leiden University Medical Center (NL61926.058.17).","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed Consent"}}]}}