{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T23:41:09Z","timestamp":1773272469063,"version":"3.50.1"},"reference-count":44,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2016,10,19]],"date-time":"2016-10-19T00:00:00Z","timestamp":1476835200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["51P30 CA46934"],"award-info":[{"award-number":["51P30 CA46934"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Increases in the mean corpuscular volume (<jats:styled-content style=\"fixed-case\">MCV<\/jats:styled-content>) have been observed in patients with metastatic renal cell carcinoma (<jats:styled-content style=\"fixed-case\">mRCC<\/jats:styled-content>) on tyrosine kinase inhibitor (<jats:styled-content style=\"fixed-case\">TKI<\/jats:styled-content>) treatment; however, its association with progression\u2010free\u2010survival (<jats:styled-content style=\"fixed-case\">PFS<\/jats:styled-content>) is unknown. We aimed to characterize <jats:styled-content style=\"fixed-case\">TKI<\/jats:styled-content>\u2010associated macrocytosis in <jats:styled-content style=\"fixed-case\">mRCC<\/jats:styled-content> and its relationship with PFS. Retrospective review of data on macrocytosis and thyroid dysfunction on <jats:styled-content style=\"fixed-case\">mRCC<\/jats:styled-content> patients treated with sunitinib and\/or sorafenib. These results are evaluated in the context of our previous report on the association of hypothyroidism in this setting. We assessed <jats:styled-content style=\"fixed-case\">PFS<\/jats:styled-content> as clinically defined by the treating physician. Seventy\u2010four patients, 29 of whom received both drugs, were included. A treatment period was defined as time from initiation to discontinuation of either sunitinib or sorafenib; 103 treatment periods [sorafenib (47), sunitinib (56)] were analyzed. Macrocytosis was found in 55 and 8% of sunitinib\u2010 and sorafenib\u2010treated patients, respectively, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001. The median time to developing macrocytosis was 3\u00a0months (m, range 1\u20137). Median <jats:styled-content style=\"fixed-case\">PFS<\/jats:styled-content> in sunitinib\u2010treated patients was 11\u00a0m (95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>: 6\u201319). Median <jats:styled-content style=\"fixed-case\">PFS<\/jats:styled-content> was higher among those with macrocytosis compared to normocytosis (21\u00a0m [95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>: 11\u201325] vs. 4\u00a0m [95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>: 3\u20138] <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0001). Macrocytosis and hypothyroidism were two significant predictors of <jats:styled-content style=\"fixed-case\">PFS<\/jats:styled-content>. The greatest difference in <jats:styled-content style=\"fixed-case\">PFS<\/jats:styled-content> among all patients was observed in patients with both macrocytosis and hypothyroidism (25\u00a0m), compared to the normocytic and euthyroid patients (5\u00a0m) (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001). Sunitinib\u2010related macrocytosis was associated with prolonged <jats:styled-content style=\"fixed-case\">PFS<\/jats:styled-content>, and concurrent development of hypothyroidism and macrocytosis further prolonged <jats:styled-content style=\"fixed-case\">PFS<\/jats:styled-content>. Increased <jats:styled-content style=\"fixed-case\">MCV<\/jats:styled-content> may have a role as a predictive biomarker for sunitinib. Prospective studies accounting for other known prognostic factors are needed to confirm this finding.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.919","type":"journal-article","created":{"date-parts":[[2016,10,19]],"date-time":"2016-10-19T06:13:35Z","timestamp":1476857615000},"page":"3386-3393","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Clinical significance of sunitinib\u2010associated macrocytosis in metastatic renal cell carcinoma"],"prefix":"10.1002","volume":"5","author":[{"given":"Maria T.","family":"Bourlon","sequence":"first","affiliation":[{"name":"Division of Medical Oncology Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n  Mexico City Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dexiang","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Informatics University of Colorado  Denver Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Trigero","sequence":"additional","affiliation":[{"name":"School of Medicine University of Colorado Denver  Aurora Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia E.","family":"Clemons","sequence":"additional","affiliation":[{"name":"School of Medicine University of Colorado Denver  Aurora Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathryn","family":"Breaker","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology Department of Medicine School of Medicine University of Colorado  Aurora Colorado"},{"name":"University of Colorado Cancer Center  Aurora Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elaine T.","family":"Lam","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology Department of Medicine School of Medicine University of Colorado  Aurora Colorado"},{"name":"University of Colorado Cancer Center  Aurora Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas W.","family":"Flaig","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology Department of Medicine School of Medicine University of Colorado  Aurora Colorado"},{"name":"University of Colorado Cancer Center  Aurora Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,10,19]]},"reference":[{"issue":"1","key":"e_1_2_8_2_1","first-page":"66","article-title":"New treatments for metastatic kidney cancer","volume":"12","author":"Mancuso A.","year":"2005","journal-title":"Can. 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