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For rare NTRK and RET fusion-positive metastatic, RAI-resistant thyroid cancers, limited and variable re-induction of RAI avidity has been reported with NTRK/RET inhibitors. Two cases with larotrectinib showed unsuccessful I-123 uptake restoration in a TERT-positive tumor, while a TERT-negative tumor achieved I-131 reuptake, indicating co-occurrence of TERT mutations and NTRK fusions may impair re-sensitization.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/predictors-of-radioiodine-rai-avidity-restoration-for-ntrk-fusion-positive-rai-resistant-metastatic-thyroid-cancers-research/337749/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/predictors-of-radioiodine-rai-avidity-restoration-for-ntrk-fusion-positive-rai-resistant-metastatic-thyroid-cancers-research/337749.png","ImageObject",300,407,{"name":92,"@type":93},"Eliana","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"Why is radioiodine (RAI) avidity restoration clinically important in metastatic differentiated thyroid cancer?","Question",{"text":113,"@type":114},"Many metastatic DTC patients become RAI-resistant, resulting in poor prognosis. Restoring RAI uptake can enable renewed effectiveness of RAI-based therapy.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What did the two reported larotrectinib cases show regarding RAI uptake?",{"text":118,"@type":114},"The TERT-positive ETV6::NTRK3 tumor failed to show successful re-induction on diagnostic I-123 scanning, whereas the TERT-negative TPR::NTRK1 tumor exhibited successful I-131 reuptake.",{"name":120,"@type":111,"acceptedAnswer":121},"How might TERT mutations influence RAI re-sensitization in NTRK fusion-positive disease?",{"text":122,"@type":114},"The report concludes that, similar to RAI resistance linked with concurrent TERT and BRAF mutations, co-occurring TERT mutations and NTRK fusions may contribute to failure of re-sensitization.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},337749,1790464186,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":52,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},4398048949847,"https://ap-avatar.wpscdn.com/avatar/400002536579ef2da7f?_k=1778318612642679267","European Thyroid Journal (2024) 13 e230227  \n[https://doi.org/10.1530/ETJ-23-0227](https://doi.org/10.1530/ETJ-23-0227)  \nRESEARCH  \nReceived 1 November 2023 Accepted 18 April 2024 Available online 18 April 2024  \nVersion of Record published 9 May 2024  \n\n| Predictors of radioiodine (RAI)-avidity restoration for NTRK fusion-positive RAI-resistant metastatic thyroid cancers\u003Cbr>Abdul Rehman Syed1, Aakash Gorana2, Erik Nohr3, Xiaoli-Kat Yuan4, Parthiv Amin MASc5, Sana Ghaznavi6, Debbie Lamb2, John McIntyre4, Markus Eszlinger7 and Ralf Paschke8\u003Cbr>1University of Calgary, Calgary, Alberta, Canada\u003Cbr>2Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Alberta, Canada\u003Cbr>3Alberta Precision Laboratories, Molecular Pathology Program, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada\u003Cbr>4Precision Oncology Hub Laboratory, Tom Baker Cancer Centre, Calgary, Alberta, Canada\u003Cbr>5Department of Radiology, Cumming School of Medicine, University of Calgary, Calgary Alberta, Canada\u003Cbr>6Arnie Charbonneau Cancer Institute, Department of Medicine, Section of Endocrinology, University of Calgary, Calgary, Alberta, Canada\u003Cbr>7Department of Oncology, Cumming School of Medicine, and Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, Alberta, Canada\u003Cbr>8Departments of Medicine, Section of Endocrinology, Oncology, Pathology and Laboratory Medicine, Biochemistry and Molecular Biology and Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada\u003Cbr>Correspondence should be addressed to R Paschke: Ralf.paschke@ucalgary.ca |\n| --- |\n| Abstract\u003Cbr>Context: Two-thirds of metastatic differentiated thyroid cancer (DTC) patients have radioiodine (RAI)-resistant disease, resulting in poor prognosis and high mortality. For rare NTRK and RET fusion-positive metastatic, RAI-resistant thyroid cancers, variable success of re-induction of RAI avidity during treatment with NTRK or RET inhibitors has been reported.\u003Cbr>Case presentation and results: We report two cases with RAI-resistant lung metastases treated with larotrectinib: an 83-year-old male presenting with an ETV6::NTRK3 fusion-positive tumor with the TERT promoter mutation c.-124C>T, and a 31-year-old female presenting with a TPR::NTRK1 fusion-positive tumor (and negative for TERT promoter mutation) . Post larotrectinib treatment, diagnostic I-123 whole body scan revealed unsuccessful RAI-uptake\u003Cbr>re-induction in the TERT-positive tumor, with a thyroid differentiation score (TDS) of −0.287. In contrast, the TERTnegative tumor exhibited successful I-131 reuptake with a TDS of −0.060.\u003Cbr>Conclusion: As observed for RAI-resistance associated with concurrent TERTand BRAF mutations, the co-occurrence of TERT mutations and NTRK fusions may also contribute to re-sensitization failure.\u003Cbr>Keywords: radioiodine uptake reinduction; radioiodine avidity restoration; NTRK fusion gene thyroid cancer; radioiodine resistance; larotrectinib |\n\nPublished by Bioscientifica Ltd.  \n[https://etj.bioscientifica.com](https://etj.bioscientifica.com)  \n© 2024 the author(s)  \nThis work is licensed under a Creative Commons Attribution 4.0 International License.  \nA R Syed et al.  \nEuropean Thyroid Journal (2024) 13 e230227  \n[https://doi.org/10.1530/ETJ-23-0227](https://doi.org/10.1530/ETJ-23-0227)  \nGraphical abstract  \nA R Syed et al.  \nEuropean Thyroid Journal (2024) 13 e230227  \n[https://doi.org/10.1530/ETJ-23-0227](https://doi.org/10.1530/ETJ-23-0227)  \nIntroduction  \nPapillary thyroid carcinoma (PTC) typically has an excellent clinical prognosis. However, 10% of cases of differentiated thyroid cancers (DTC) will progress to a metastatic stage after receiving initial treatment (1) . Two-thirds of metastatic DTCs lose their ability to uptake radioiodine (RAI) due to oncogene driver mutations silencing thyroid iodide-metabolizing genes, causing them to be RAI-resistant or refractory (1, 2, 3) . Patients w","cbCaiejcNSTpNFvT","https://ap.wps.com/l/cbCaiejcNSTpNFvT","pdf",2383285,"English","# Abstract\n## Introduction\n## Case presentation and results\n## Conclusion","[{\"question\":\"Why is radioiodine (RAI) avidity restoration clinically important in metastatic differentiated thyroid cancer?\",\"answer\":\"Many metastatic DTC patients become RAI-resistant, resulting in poor prognosis. Restoring RAI uptake can enable renewed effectiveness of RAI-based therapy.\"},{\"question\":\"What did the two reported larotrectinib cases show regarding RAI uptake?\",\"answer\":\"The TERT-positive ETV6::NTRK3 tumor failed to show successful re-induction on diagnostic I-123 scanning, whereas the TERT-negative TPR::NTRK1 tumor exhibited successful I-131 reuptake.\"},{\"question\":\"How might TERT mutations influence RAI re-sensitization in NTRK fusion-positive disease?\",\"answer\":\"The report concludes that, similar to RAI resistance linked with concurrent TERT and BRAF mutations, co-occurring TERT mutations and NTRK fusions may contribute to failure of re-sensitization.\"}]","Predictors of radioiodine (RAI)-avidity restoration for NTRK fusion-positive RAI-resistant metastatic thyroid cancers - Research | PDF",1790020477,25]