{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T16:22:15Z","timestamp":1788452535470,"version":"build-2803163510"},"reference-count":34,"publisher":"The Endocrine Society","issue":"9","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007514","name":"Clinical and Translational Science of the University of Pisa","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007514","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Italian Ministry of University and Research","doi-asserted-by":"publisher","award":["2017YTWKWH"],"award-info":[{"award-number":["2017YTWKWH"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Italian Ministry of University and Research","doi-asserted-by":"publisher","award":["PE_00000019"],"award-info":[{"award-number":["PE_00000019"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Italian Ministry of University and Research","doi-asserted-by":"publisher","award":["I53C22001440006"],"award-info":[{"award-number":["I53C22001440006"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>The predictive role of mutational status in the response to lenvatinib in advanced radioiodine-refractory thyroid cancer (RAIR-TC) is not yet defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To identify a molecular signature of RAIR-TC treated with lenvatinib and its impact on clinical response to lenvatinib.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>This is a retrospective study including 49 RAIR-TC patients treated with first-line lenvatinib and followed at least 1 year [median follow-up 9.2 years (interquartile range 6-14.1)]. Next-generation sequencing on tissues was used to detect genetic alterations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>The study was performed in a referral center for the treatment of thyroid cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 49 cases, BRAF (38.7%) and RAS (22.4%) were the most frequent driver mutations, while TERT and TP53 were mutated in 57.1% and 6.1%. No driver mutations were found in 34.6%. Driver mutations co-occurred with TERT or TP53 in 44.9%. In 10\/49 (20.4%), no mutations were found. Cases with \u22651 mutation had longer progression-free survival (PFS) than cases negative for any mutation (P = .004). Both BRAF-mutated and RAS-mutated cases showed better PFS and overall survival (OS), although this was not statistically significant with respect to wild-type cases. Cases with a single driver mutation (group 1) showed longer PFS than cases without driver mutations (group 3) (P = .04) but no difference with cases with driver + TERT or TP53 (group 2) (P = .13). Group 1 showed longer OS than group 2 (P = .026) and group 3 (P = .034).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The RAIR-TC molecular profile is heterogeneous with TERT being the most frequent mutation. Cases negative for all mutations and cases presenting the coexistence of TERT + driver mutation had a worse response to lenvatinib. Conversely, the presence of 1 driver mutation correlated with a better response to lenvatinib.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgag074","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T12:48:27Z","timestamp":1774529307000},"page":"2525-2535","source":"Crossref","is-referenced-by-count":2,"title":["Molecular Profile of Advanced Radioiodine-refractory Thyroid Cancer and Response to Lenvatinib Treatment"],"prefix":"10.1210","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4144-4906","authenticated-orcid":false,"given":"Elisa","family":"Minaldi","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Endocrinology Unit, University of Pisa , Pisa 56124 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Ramone","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, 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