{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:01:47Z","timestamp":1791896507484,"version":"4.3.4"},"reference-count":41,"publisher":"The Endocrine Society","issue":"12","license":[{"start":{"date-parts":[[2024,2,13]],"date-time":"2024-02-13T00:00:00Z","timestamp":1707782400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Risk factors for radioactive iodine (RAI)-refractory disease in follicular (FTC) and oncocytic thyroid carcinoma (OTC) are unknown.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>The aim of this study is to identify clinical and histopathological risk factors for RAI-refractory disease in FTC and OTC patients, facilitated by an extensive histopathological revision.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>All adult FTC and OTC patients treated at Erasmus MC (the Netherlands) between 2000 and 2016 were retrospectively included. The 2015 American Thyroid Association guidelines were used to define RAI-refractory disease. An extensive histopathological revision was performed applying the 2022 World Health Organization Classification using PALGA, the Dutch Pathology Databank. Logistic regression was used to identify risk factors for RAI-refractory disease, stratified by histological subtype.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Ninety FTC and 52 OTC patients were included, of whom 14 FTC (15.6%) and 22 OTC (42.3%) patients developed RAI-refractory disease over a follow-up time of 8.5 years. RAI-refractory disease occurred in OTC after fewer cycles than in FTC (2.0 [interquartile range (IQR): 1.0-2.0] vs 2.5 [IQR: 2.0-3.75]), and it substantially decreased 10-year disease-specific survival, especially in OTC (46.4%; FTC 85.7%). In FTC, risk factors were higher age at diagnosis, pT3\/pT4 stage, N1 stage, widely invasive tumors, and extrathyroidal extension. N1 stage and M1 stage were the strongest risk factors in OTC, rather than histopathological characteristics of the primary tumor.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>To our knowledge, this is the first study that correlates clinical and histopathological risk factors with RAI-refractory disease in FTC and OTC, facilitated by a histopathological revision. In FTC, risk factors for RAI-refractory disease were foremost histopathological characteristics of the primary tumor, whereas in OTC presentation with lymph node and distant metastasis was associated with RAI-refractory disease. Our data can help clinical decision-making, particularly in patients at risk for RAI-refractory disease.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgae084","type":"journal-article","created":{"date-parts":[[2024,2,13]],"date-time":"2024-02-13T14:31:54Z","timestamp":1707834714000},"page":"e2334-e2341","source":"Crossref","is-referenced-by-count":15,"title":["Clinical and Histopathological Risk Factors for Radioactive Iodine\u2013Refractory Follicular and Oncocytic Thyroid Carcinoma"],"prefix":"10.1210","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1096-8564","authenticated-orcid":false,"given":"Merel T","family":"Stegenga","sequence":"first","affiliation":[{"name":"Erasmus MC Academic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical Center , 3015 GD Rotterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6938-065X","authenticated-orcid":false,"given":"Evert F S","family":"van Velsen","sequence":"additional","affiliation":[{"name":"Erasmus MC Academic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical Center , 3015 GD Rotterdam ,","place":["the Netherlands"]},{"name":"Erasmus MC Bone Center, Department of Internal Medicine, Erasmus Medical Center , 3015 GD Rotterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6168-2381","authenticated-orcid":false,"given":"Lindsey","family":"Oudijk","sequence":"additional","affiliation":[{"name":"Erasmus MC Academic Center for Thyroid Diseases, Department of Pathology, Erasmus Medical Center , 3015 GD Rotterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederik A","family":"Verburg","sequence":"additional","affiliation":[{"name":"Erasmus MC Academic Center for Thyroid Diseases, Department of Radiology and Nuclear Medicine, Erasmus Medical Center , 3015 GD Rotterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tessa M","family":"van Ginhoven","sequence":"additional","affiliation":[{"name":"Erasmus MC Academic Center for Thyroid Disease, Department of Surgery, Erasmus Medical Center , 3015 GD Rotterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7732-9371","authenticated-orcid":false,"given":"Robin P","family":"Peeters","sequence":"additional","affiliation":[{"name":"Erasmus MC Academic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical Center , 3015 GD Rotterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7271-7858","authenticated-orcid":false,"given":"Marco","family":"Medici","sequence":"additional","affiliation":[{"name":"Erasmus MC Academic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical Center , 3015 GD Rotterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5248-863X","authenticated-orcid":false,"given":"W Edward","family":"Visser","sequence":"additional","affiliation":[{"name":"Erasmus MC Academic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical Center , 3015 GD Rotterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4225-4354","authenticated-orcid":false,"given":"Folkert J","family":"van Kemenade","sequence":"additional","affiliation":[{"name":"Erasmus MC Academic Center for Thyroid Diseases, Department of Pathology, Erasmus Medical Center , 3015 GD Rotterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2024,2,13]]},"reference":[{"issue":"4","key":"2024111804003874900_dgae084-B1","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1001\/jamaoto.2014.1","article-title":"Current thyroid cancer trends in the United States","volume":"140","author":"Davies","year":"2014","journal-title":"JAMA Otolaryngol Head Neck Surg"},{"issue":"8","key":"2024111804003874900_dgae084-B2","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1089\/thy.2012.0356","article-title":"Follicular thyroid cancer incidence patterns in the United States, 1980-2009","volume":"23","author":"Aschebrook-Kilfoy","year":"2013","journal-title":"Thyroid"},{"issue":"3","key":"2024111804003874900_dgae084-B3","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1002\/cncr.27770","article-title":"Hurthle cell carcinoma: a population-level analysis of 3311 patients","volume":"119","author":"Goffredo","year":"2013","journal-title":"Cancer"},{"issue":"6","key":"2024111804003874900_dgae084-B4","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1016\/j.surg.2013.06.029","article-title":"Hurthle cell carcinoma: an update on survival over the last 35 years","volume":"154","author":"Nagar","year":"2013","journal-title":"Surgery"},{"issue":"1","key":"2024111804003874900_dgae084-B5","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1186\/s12885-017-3370-x","article-title":"Survival and prognostic factors for survival, cancer specific survival and disease free interval in 239 patients with hurthle cell carcinoma: a single center experience","volume":"17","author":"Oluic","year":"2017","journal-title":"BMC Cancer"},{"issue":"5","key":"2024111804003874900_dgae084-B6","doi-asserted-by":"crossref","first-page":"E962","DOI":"10.1210\/jc.2012-3539","article-title":"Genomic dissection of hurthle cell carcinoma reveals a unique class of thyroid malignancy","volume":"98","author":"Ganly","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"key":"2024111804003874900_dgae084-B7","volume-title":"WHO Classification of Tumours of Endocrine Organs","author":"Lloyd","year":"2017","edition":"4th ed"},{"issue":"1","key":"2024111804003874900_dgae084-B8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1089\/thy.2015.0020","article-title":"2015 American thyroid association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American thyroid association guidelines task force on thyroid nodules and differentiated thyroid cancer","volume":"26","author":"Haugen","year":"2016","journal-title":"Thyroid"},{"issue":"8","key":"2024111804003874900_dgae084-B9","doi-asserted-by":"crossref","first-page":"2892","DOI":"10.1210\/jc.2005-2838","article-title":"Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: benefits and limits of radioiodine therapy","volume":"91","author":"Durante","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"issue":"5","key":"2024111804003874900_dgae084-B10","doi-asserted-by":"crossref","first-page":"R57","DOI":"10.1530\/ERC-22-0006","article-title":"Advanced RAI-refractory thyroid cancer: an update on treatment perspectives","volume":"29","author":"Karapanou","year":"2022","journal-title":"Endocr Relat Cancer"},{"issue":"6","key":"2024111804003874900_dgae084-B11","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1210\/er.2019-00007","article-title":"Targeted therapy for advanced thyroid cancer: kinase inhibitors and beyond","volume":"40","author":"Cabanillas","year":"2019","journal-title":"Endocr Rev"},{"issue":"8","key":"2024111804003874900_dgae084-B12","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1089\/thy.2016.0578","article-title":"Information for clinicians: approach to the patient with progressive radioiodine-refractory thyroid cancer-when to use systemic therapy","volume":"27","author":"Cabanillas","year":"2017","journal-title":"Thyroid"},{"key":"2024111804003874900_dgae084-B13","doi-asserted-by":"crossref","first-page":"549882","DOI":"10.3389\/fonc.2020.549882","article-title":"Clinical, pathological, and molecular characteristics correlating to the occurrence of radioiodine refractory differentiated thyroid carcinoma: a systematic review and meta-analysis","volume":"10","author":"Luo","year":"2020","journal-title":"Front Oncol"},{"issue":"6","key":"2024111804003874900_dgae084-B14","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1089\/thy.2017.0102","article-title":"Updated American joint committee on cancer\/tumor-node-metastasis staging system for differentiated and anaplastic thyroid cancer (eighth edition): what changed and why?","volume":"27","author":"Tuttle","year":"2017","journal-title":"Thyroid"},{"key":"2024111804003874900_dgae084-B15"},{"issue":"1","key":"2024111804003874900_dgae084-B16","first-page":"19","article-title":"Pathology databanking and biobanking in The Netherlands, a central role for PALGA, the nationwide histopathology and cytopathology data network and archive","volume":"29","author":"Casparie","year":"2007","journal-title":"Cell Oncol"},{"key":"2024111804003874900_dgae084-B17","volume-title":"WHO Classification of Tumours Endocrine and Neuroendocrine Tumours","author":"Ghossein","year":"2022","edition":"5th ed"},{"key":"2024111804003874900_dgae084-B18","unstructured":"Stegenga M. SuppTable1Stegenga_RAIR_22.01.2024.docx. figshare. 2024. Doi:10.6084\/m9.figshare.25067708.v2"},{"issue":"10","key":"2024111804003874900_dgae084-B19","doi-asserted-by":"crossref","first-page":"e3911","DOI":"10.1210\/clinem\/dgab436","article-title":"Avidity and outcomes of radioiodine therapy for distant metastasis of distinct types of differentiated thyroid cancer","volume":"106","author":"Sim\u00f5es-Pereira","year":"2021","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"2024111804003874900_dgae084-B20","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1089\/105072503322238845","article-title":"The role of radioactive iodine in the treatment of hurthle cell carcinoma of the thyroid","volume":"13","author":"Besic","year":"2003","journal-title":"Thyroid"},{"issue":"2","key":"2024111804003874900_dgae084-B21","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1007\/s00259-020-04952-2","article-title":"Clinical impact of follicular oncocytic (hurthle cell) carcinoma in comparison with corresponding classical follicular thyroid carcinoma","volume":"48","author":"Wenter","year":"2021","journal-title":"Eur J Nucl Med Mol Imaging"},{"issue":"5","key":"2024111804003874900_dgae084-B22","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1089\/thy.2019.0688","article-title":"Patient age is an independent risk factor of relapse of differentiated thyroid carcinoma and improves the performance of the American thyroid association stratification system","volume":"30","author":"Trimboli","year":"2020","journal-title":"Thyroid"},{"issue":"2","key":"2024111804003874900_dgae084-B23","doi-asserted-by":"crossref","first-page":"258","DOI":"10.2967\/jnumed.116.180240","article-title":"TERT promoter mutation predicts radioiodine-refractory character in distant metastatic differentiated thyroid cancer","volume":"58","author":"Yang","year":"2017","journal-title":"J Nucl Med"},{"issue":"9","key":"2024111804003874900_dgae084-B24","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1089\/thy.2019.0075","article-title":"Clinical, pathological, and molecular profiling of radioactive iodine refractory differentiated thyroid cancer","volume":"29","author":"Shobab","year":"2019","journal-title":"Thyroid"},{"issue":"7","key":"2024111804003874900_dgae084-B25","doi-asserted-by":"crossref","first-page":"e0179664","DOI":"10.1371\/journal.pone.0179664","article-title":"Quantitative thyroglobulin response to radioactive iodine treatment in predicting radioactive iodine-refractory thyroid cancer with pulmonary metastasis","volume":"12","author":"Wang","year":"2017","journal-title":"PLoS One"},{"issue":"11","key":"2024111804003874900_dgae084-B26","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1089\/thy.2019.0459","article-title":"Risk stratification using a novel genetic classifier including PLEKHS1 promoter mutations for differentiated thyroid cancer with distant metastasis","volume":"30","author":"Jung","year":"2020","journal-title":"Thyroid"},{"issue":"11","key":"2024111804003874900_dgae084-B27","doi-asserted-by":"crossref","first-page":"5448","DOI":"10.1002\/cam4.1794","article-title":"Radioiodine refractoriness score: a multivariable prediction model for postoperative radioiodine-refractory differentiated thyroid carcinomas","volume":"7","author":"Li","year":"2018","journal-title":"Cancer Med"},{"issue":"1","key":"2024111804003874900_dgae084-B28","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1634\/theoncologist.2015-0107","article-title":"Outcomes and prognostic factors in radioiodine refractory differentiated thyroid carcinomas","volume":"21","author":"Wassermann","year":"2016","journal-title":"Oncologist"},{"issue":"12","key":"2024111804003874900_dgae084-B29","doi-asserted-by":"crossref","first-page":"2845","DOI":"10.1007\/s00268-013-2213-4","article-title":"Prognostic implications of radioiodine avidity and serum thyroglobulin in differentiated thyroid carcinoma with distant metastasis","volume":"37","author":"Kim","year":"2013","journal-title":"World J Surg"},{"issue":"9940","key":"2024111804003874900_dgae084-B30","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0140-6736(14)60421-9","article-title":"Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial","volume":"384","author":"Brose","year":"2014","journal-title":"Lancet"},{"issue":"9","key":"2024111804003874900_dgae084-B31","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1586\/era.12.96","article-title":"Regional approaches to the management of patients with advanced, radioactive iodine-refractory differentiated thyroid carcinoma","volume":"12","author":"Brose","year":"2012","journal-title":"Expert Rev Anticancer Ther"},{"issue":"5","key":"2024111804003874900_dgae084-B32","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/S2213-8587(13)70215-8","article-title":"Definition and management of radioactive iodine-refractory differentiated thyroid cancer","volume":"2","author":"Schlumberger","year":"2014","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"7","key":"2024111804003874900_dgae084-B33","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.2967\/jnumed.115.168799","article-title":"Dose-Response relationship in differentiated thyroid cancer patients undergoing radioiodine treatment assessed by means of 124I PET\/CT","volume":"57","author":"Wierts","year":"2016","journal-title":"J Nucl Med"},{"issue":"1","key":"2024111804003874900_dgae084-B34","first-page":"143","article-title":"Prediction of absorbed dose to normal organs in thyroid cancer patients treated with 131I by use of 124I PET and 3-dimensional internal dosimetry software","volume":"48","author":"Kolbert","year":"2007","journal-title":"J Nucl Med"},{"issue":"3","key":"2024111804003874900_dgae084-B35","doi-asserted-by":"crossref","first-page":"R161","DOI":"10.1677\/ERC-10-0071","article-title":"Dosimetry and thyroid cancer: the individual dosage of radioiodine","volume":"17","author":"Lassmann","year":"2010","journal-title":"Endocr Relat Cancer"},{"issue":"4","key":"2024111804003874900_dgae084-B36","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1089\/thy.2018.0597","article-title":"Controversies, consensus, and collaboration in the use of (131)I therapy in differentiated thyroid cancer: a joint statement from the American thyroid association, the European association of nuclear medicine, the society of nuclear medicine and molecular imaging, and the European thyroid association","volume":"29","author":"Tuttle","year":"2019","journal-title":"Thyroid"},{"issue":"11","key":"2024111804003874900_dgae084-B37","doi-asserted-by":"crossref","first-page":"3144","DOI":"10.1210\/clinem\/dgac448","article-title":"Radioactive iodine therapy does not improve cancer-specific survival in hurthle cell carcinoma of the thyroid","volume":"107","author":"Wang","year":"2022","journal-title":"J Clin Endocrinol Metab"},{"issue":"7","key":"2024111804003874900_dgae084-B38","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1089\/thy.2020.0615","article-title":"Finding the optimal age cutoff for the UICC\/AJCC TNM staging system in patients with papillary or follicular thyroid cancer","volume":"31","author":"van Velsen","year":"2021","journal-title":"Thyroid"},{"issue":"3","key":"2024111804003874900_dgae084-B39","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1530\/EJE-21-1056","article-title":"Evaluating the use of a two-step age-based cutoff for the UICC\/AJCC TNM staging system in patients with papillary or follicular thyroid cancer","volume":"186","author":"van Velsen","year":"2022","journal-title":"Eur J Endocrinol"},{"issue":"3","key":"2024111804003874900_dgae084-B40","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1530\/EJE-21-0365","article-title":"The influence of age on disease outcome in 2015 ATA high-risk differentiated thyroid cancer patients","volume":"185","author":"van Velsen","year":"2021","journal-title":"Eur J Endocrinol"},{"issue":"7","key":"2024111804003874900_dgae084-B41","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1056\/NEJMoa1406470","article-title":"Lenvatinib versus placebo in radioiodine-refractory thyroid cancer","volume":"372","author":"Schlumberger","year":"2015","journal-title":"N Engl J Med"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgae084\/56768965\/dgae084.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/109\/12\/e2334\/60680299\/dgae084.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/109\/12\/e2334\/60680299\/dgae084.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T04:01:05Z","timestamp":1731902465000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/109\/12\/e2334\/7607029"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,13]]},"references-count":41,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,2,13]]},"published-print":{"date-parts":[[2024,11,18]]}},"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgae084","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,12]]},"published":{"date-parts":[[2024,2,13]]}}}