{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:20:33Z","timestamp":1784557233002,"version":"3.55.0"},"reference-count":22,"publisher":"Bioscientifica","issue":"5","license":[{"start":{"date-parts":[[2017,5,1]],"date-time":"2017-05-01T00:00:00Z","timestamp":1493596800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:p>There are limited treatment options for patients with radioactive iodine refractory, progressive differentiated thyroid cancer. Although there is consensus that multikinase inhibitor therapy should be considered in patients with progressive disease with considerable tumor load or symptomatic disease, uncertainty exists on the optimal timing to treat with a multikinase inhibitor, especially for asymptomatic patients. RIFTOS MKI is an international, prospective, open-label, multicenter, noninterventional study with the primary objective to compare the time to symptomatic progression from study entry in asymptomatic patients with radioactive iodine refractory, progressive differentiated thyroid cancer for whom there is a decision to initiate multikinase inhibitors at study entry (cohort 1) with those for whom there is a decision to not initiate multikinase inhibitors at study entry (cohort 2). Secondary endpoints are overall survival and progression-free survival, which will be compared between cohorts 1 and 2. Additional secondary endpoints are postprogression survival from time of symptomatic progression, duration of and response to each systemic treatment regimen and dosing of sorafenib throughout the treatment period. Asymptomatic, multikinase inhibitor-naive patients aged \u226518 years with histologically\/cytologically documented differentiated thyroid cancer that is radioactive iodine refractory are eligible. Patients may receive any therapy for differentiated thyroid cancer, including sorafenib or other multikinase inhibitors if indicated and decided on by the treating physician. In total, 700 patients are estimated to be enrolled from &gt;20 countries. Final analysis will be performed once the last enrolled patient has been followed up with for 24 months (ClinicalTrials.gov identifier: Nbib2303444).<\/jats:p>","DOI":"10.1530\/erc-17-0016","type":"journal-article","created":{"date-parts":[[2017,3,7]],"date-time":"2017-03-07T20:30:23Z","timestamp":1488918623000},"page":"237-242","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":32,"title":["Timing of multikinase inhibitor initiation in differentiated thyroid cancer"],"prefix":"10.1530","volume":"24","author":[{"given":"Marcia S","family":"Brose","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Smit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Chi","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Pitoia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Fellous","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoriko","family":"DeSanctis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Schlumberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Tori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iwao","family":"Sugitani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"2017041817104247000_24.5.237.1","doi-asserted-by":"publisher","DOI":"10.1080\/00273171.2011.568786"},{"key":"2017041817104247000_24.5.237.2","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0b013e31814697d9"},{"key":"2017041817104247000_24.5.237.3","doi-asserted-by":"publisher","DOI":"10.1586\/era.12.96"},{"key":"2017041817104247000_24.5.237.4","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)60421-9"},{"key":"2017041817104247000_24.5.237.5","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminoncol.2010.10.008"},{"key":"2017041817104247000_24.5.237.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.09.050"},{"key":"2017041817104247000_24.5.237.7","doi-asserted-by":"publisher","first-page":"3270","DOI":"10.1210\/JC.2015-1346","article-title":"Long-term outcomes following therapy in differentiated thyroid carcinoma: NTCTCS registry analysis 1987\u20132012","volume":"100","author":"Carhill","year":"2015","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"2017041817104247000_24.5.237.8","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2006.16.109"},{"key":"2017041817104247000_24.5.237.9","first-page":"335","article-title":"Optimizing therapy for radioactive iodine-refractory differentiated thyroid cancer: current state of the art and future directions","volume":"37","author":"Dadu","year":"2012","journal-title":"Minerva Endocrinologica"},{"key":"2017041817104247000_24.5.237.10","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-2838"},{"key":"2017041817104247000_24.5.237.11","doi-asserted-by":"publisher","DOI":"10.1097\/COC.0b013e3182468039"},{"key":"2017041817104247000_24.5.237.12","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2015.0020"},{"key":"2017041817104247000_24.5.237.13","first-page":"32","article-title":"Clinical development of kinase inhibitors for the treatment of differentiated thyroid cancer","volume":"9","author":"Ho","year":"2011","journal-title":"Clinical Advances in Hematology and Oncology"},{"key":"2017041817104247000_24.5.237.14","first-page":"1454","article-title":"High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET\/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma","volume":"63","author":"Kimura","year":"2003","journal-title":"Cancer Research"},{"key":"2017041817104247000_24.5.237.15","doi-asserted-by":"publisher","DOI":"10.1172\/JCI85271"},{"key":"2017041817104247000_24.5.237.16","unstructured":"National Comprehensive Cancer Network 2015 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): thyroid carcinoma, version 1.2015. 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