{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T14:17:25Z","timestamp":1786371445416,"version":"build-2736575974"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"15","license":[{"start":{"date-parts":[[2023,8,7]],"date-time":"2023-08-07T00:00:00Z","timestamp":1691366400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,8,7]],"date-time":"2023-08-07T00:00:00Z","timestamp":1691366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Munich Clinician Scientist Program Track F\u00f6FoLe+,  medical faculty of the LMU Munich","award":["Reg.-Nr. 044"],"award-info":[{"award-number":["Reg.-Nr. 044"]}]},{"name":"Universit\u00e4tsklinik M\u00fcnchen"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Cancer Res Clin Oncol"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>Pathogenic fusion events involving neurotrophic receptor tyrosine kinase (NTRK) have been described in\u2009~\u20092% of differentiated thyroid cancer (DTC). The selective tropomyosin receptor kinase (TRK) inhibitors entrectinib and larotrectinib have been approved in a tumor agnostic manner based on phase 1\/2 clinical trials. In a real-world setting at five referral centers, we aimed to describe the prevalence of <jats:italic>NTRK<\/jats:italic> gene fusions and the efficacy and safety of TRK inhibitor treatment for non-medullary, advanced thyroid cancer (TC).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>A total of 184 TC patients with testing for <jats:italic>NTRK<\/jats:italic> gene fusions were included. Progression-free survival (PFS) and overall survival (OS) probabilities were estimated using the Kaplan\u2013Meier method in six patients with <jats:italic>NTRK<\/jats:italic> fusion-positive TC who underwent TRK inhibitor therapy.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>8\/184 (4%) patients harbored <jats:italic>NTRK<\/jats:italic> gene fusions. Six patients with radioiodine (RAI)-refractory TC harboring <jats:italic>NTRK1<\/jats:italic> (<jats:italic>n<\/jats:italic>\u2009=\u20094) and <jats:italic>NTRK3<\/jats:italic> (<jats:italic>n<\/jats:italic>\u2009=\u20092) gene fusions were treated with larotrectinib. Five patients (83%) had received\u2009\u2265\u20091 prior systemic therapy and one patient did not receive prior systemic therapy. All patients had morphologically progressive disease before treatment initiation. Objective response rate was 83%, including two complete remissions. Median PFS from start of TRK inhibitor treatment was 23\u00a0months (95% confidence interval [CI], 0\u201357.4) and median OS was not reached (NR) (95% CI, NR). Adverse events were of grade 1\u20133.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>The prevalence of <jats:italic>NTRK<\/jats:italic> gene fusions in our cohort of RAI-refractory TC is slightly higher than reported for all TC patients. Larotrectinib is an effective treatment option in the majority of <jats:italic>NTRK<\/jats:italic> gene fusion-positive advanced TC patients after prior systemic treatment and has a favorable safety profile.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00432-023-05134-x","type":"journal-article","created":{"date-parts":[[2023,8,7]],"date-time":"2023-08-07T14:01:56Z","timestamp":1691416916000},"page":"14035-14043","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["NTRK fusion events and targeted treatment of advanced radioiodine refractory thyroid cancer"],"prefix":"10.1007","volume":"149","author":[{"given":"Viktoria Florentine","family":"Koehler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josefine","family":"Achterfeld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Sandner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Koch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas Paul","family":"Wiegmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Ivanyi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"K\u00e4smann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renate","family":"Pusch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihaela","family":"Chirica","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Kn\u00f6sel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie-Christin","family":"Demes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joerg","family":"Kumbrink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Vogl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gesine","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Spitzweg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joerg","family":"Bojunga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Kroiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,8,7]]},"reference":[{"issue":"1","key":"5134_CR1","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/s12022-022-09707-3","volume":"33","author":"ZW Baloch","year":"2022","unstructured":"Baloch ZW, Asa SL, Barletta JA, Ghossein RA, Juhlin CC, Jung CK, Mete O (2022) Overview of the 2022 WHO classification of thyroid neoplasms. 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Koehler has received honoraria for lectures and travel expenses from Novartis and Sanofi. Christine Koch received honoraria for advisory boards and lectures from Ipsen, Eisei, MSD, BMS, Astra Zeneca, Bayer. Philipp Ivanyi has received\u00a0advisory fees from\u00a0BMS, Bayer, ClinSol, Deciphera, EISAI, EMD-Serono, EUSA, H5-Oncology, Ipsen, Merck Serono (Global), Metaplan, MSD, Onkowissen, Pfizer, Roche, honoraria for lectures\u00a0from AIM, Apogepha, Astra Zeneca, Astella, BMS, Bayer (+\u2009Europe, Global), CORE2ED, Deciphera, DKG-Onkoweb, EISAI, EUSA, FoFM, Id-Institut, Ipsen (Europe), Merck Serono (+\u2009Europe, Global), MSD, MedKom, MTE-Academy, MedWiss, New Concept Oncology, Onkowissen-tv.de, Pharma Mare, Pfizer, Roche, ThinkWired!, Schmitz-Communikation, StreamedUP!, Solution Academy, Vivantis, research grants from\u00a0AIO, AstraZeneca, BMS, GSK, Ipsen, Lilly, Merck Serono, Nieders\u00e4chsische Krebsgesellschaft, Novartis, EUSA, EISAI, Pfizer, MSD, Roche, Stiftung Immunonkologie, Wilhelm Sander Stiftung,\u00a0travel grants from\u00a0BB-Biotech, BMS, Bayer, Deutsche Gesellschaft f\u00fcr Thoraxchirurgie, EUSA, Ipsen, Merck, Pharma Mare,\u00a0non-financial grants\u00a0from Member of Germen Working Party Medical Oncology (AIO), Member of the German Cancer Society, ASCO Member, ESMO Member, Member of Oncological Working Party Hannover (OAK), Spokesman Interdisciplinary Working Party \u2013 Kidney Cancer (IAGN-DKG), Steering Board Immunooncology Cooperative Group (ICOG-H), Clinical Trail Streering Committee CCC-H. Lukas K\u00e4smann has received honoraria for lectures from AMGEN and the German Cancer Society, and an unrestricted research grant from AstraZeneca. Melanie-Christin Demes received honoraria from talks and advisory board role from Amgen, AstraZeneca, Bayer, Biocartis, Diaceutics, Roche, Sophia Genetics und ThermoFisher. Christine Spitzweg has received honoraria for advisory boards and lectures from Ipsen, Lilly, Bayer, Eisai, Genzyme.\u00a0Matthias Kroiss has received institutional research support from Ipsen, Loxo Oncology and Lilly, travel support from Eisai, Ipsen, HRA Pharma, MCI Germany and Lilly, honoraria for lectures from Bristol-Myers Squibb, Eisai, Lilly, and MSD and consultancy honoraria from Lilly and Bayer. Josefine Achterfeld, Natalie Sandner, Jonas Paul Wiegmann,\u00a0Renate Pusch, Dominik Wolf,\u00a0Mihaela Chirica, Thomas Kn\u00f6sel, Joerg Kumbrink, Thomas J Vogl, Gesine Meyer, and Joerg Bojunga\u00a0have no competing financial interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of University W\u00fcrzburg [96\/13] and subsequently by the ethics of all participating centers or by a waiver of informed consent, approved by the local institutional review boards for this minimal risk study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"A waiver of informed consent was applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}}]}}