{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T21:44:12Z","timestamp":1788212652419,"version":"build-2803163510"},"reference-count":21,"publisher":"The Endocrine Society","issue":"9","license":[{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Metastatic medullary thyroid carcinoma (MTC) and radioactive iodine\u2013refractory differentiated thyroid carcinoma (RAI-R DTC) have poor prognosis and limited treatment options. Selpercatinib (LOXO-292), a selective kinase inhibitor targeting the RET gene, has shown a 69% to 79% objective response rate in this cohort with benefits in other tumors including lung cancer harboring the same oncogenic driver. Published reports describe only 17% of patients experiencing gastrointestinal (GI) adverse effects (AEs), which is in contrast to our local experience.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Here we characterize the AEs and correlate them with radiological and histopathological findings.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Sequential patients enrolled in LIBRETTO-001 at Royal North Shore Hospital, Sydney, Australia, with available imaging (n\u2005=\u200522) were recruited. Patients had regular visits with AEs documented and computed tomography (CT) scans every 3 months. CT at screening, at time of GI AE, and at most recent follow-up were reviewed and scored. Endoscopic examination was performed in 5 patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Of 22 patients in this cohort, the majority had somatic RET alterations (n\u2005=\u200518), most commonly p.Met918Thr (n\u2005=\u200514). Ten patients (50%) developed GI AEs. Dose reduction was required in 8 of the 10 patients, but none discontinued therapy. The majority had stable disease (n\u2005=\u200517). Gastric and small-bowel edema was evident in symptomatic patients after a median time of 67 weeks\u2019 treatment. Histological correlation in 5 patients revealed mucosal edema correlating with radiological evidence of congestion and edema.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>GI AEs with selpercatinib may be more common than previously described. Most are self-limiting but often require dose adjustments. Histological evidence of mucosal edema observed in conjunction with the radiological findings of congestion and wall thickening suggest bowel-wall edema is a predominant mechanism of abdominal pain in these patients.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgac337","type":"journal-article","created":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T14:20:52Z","timestamp":1654093252000},"page":"e3824-e3829","source":"Crossref","is-referenced-by-count":26,"title":["Selpercatinib Treatment of <i>RET<\/i>-Mutated Thyroid Cancers Is Associated With Gastrointestinal Adverse Effects"],"prefix":"10.1210","volume":"107","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7583-9175","authenticated-orcid":false,"given":"Venessa","family":"Tsang","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Royal North Shore Hospital , NSW 2065, Sydney , Australia"},{"name":"Northern Clinical School, Faculty of Medicine and Health, University of Sydney , NSW 2006 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