Mitchell S von Itzstein, Amrit S Gonugunta, Yiqing Wang, Thomas Sheffield, Rong Lu, Sadia Ali, Farjana J Fattah, Donglu Xie, Jennifer Cai, Yang Xie, David E Gerber
{"title":"在接受免疫检查点抑制剂治疗的患者中，预先存在的甲状腺功能障碍和治疗后出现的甲状腺功能障碍对预后的不同影响。","authors":"Mitchell S von Itzstein, Amrit S Gonugunta, Yiqing Wang, Thomas Sheffield, Rong Lu, Sadia Ali, Farjana J Fattah, Donglu Xie, Jennifer Cai, Yang Xie, David E Gerber","doi":"10.1007/s00262-022-03151-2","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Thyroid dysfunction is among the most common autoimmune diseases and immune checkpoint inhibitor (ICI)-induced immune-related adverse events (irAE). We determined the association between longitudinal thyroid function and clinical outcomes in patients treated with ICI.</p><p><strong>Methods: </strong>We identified all patients treated with ICI at UT Southwestern Medical Center from January 1, 2011, through December 31, 2020. We defined normal thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels according to institutional reference range. We defined clinical thyroid dysfunction using established criteria incorporating labs and treatment. We determined the association between thyroid function and overall survival (OS) using Kaplan-Meier curves, log-rank tests, and multivariate Cox proportional hazards model.</p><p><strong>Results: </strong>A total of 1781 patients were included in analyses, of whom 381 (21%) had abnormal baseline TSH. Patients with abnormal baseline TSH were more likely to be female, have kidney cancer, and initiate levothyroxine after ICI initiation (all P < 0.001). Patients with abnormal baseline TSH had inferior OS (median 16 vs 27 months; P < 0.001). Among patients with normal baseline TSH, those who had abnormal TSH after ICI initiation had improved OS (median 41 vs 22 months; P < 0.001). In a multivariate Cox model, abnormal baseline TSH was associated with worse OS (HR 1.62; 95% CI, 1.30-2.02; P < 0.001), while initiation of levothyroxine after ICI initiation was associated with improved OS (HR 0.62; 95% CI, 0.44-0.88; P = 0.008).</p><p><strong>Conclusions: </strong>ICI-induced thyroid dysfunction is associated with improved survival, although abnormal TSH prior to ICI initiation is associated with inferior survival.</p><p><strong>Precis: </strong>Thyroid abnormalities occur commonly in the general population and as immunotherapy toxicities. We found that immunotherapy-induced thyroid dysfunction is associated with better survival, but pre-existing thyroid abnormalities convey worse outcomes.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":"2169-2181"},"PeriodicalIF":0.0000,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9308834/pdf/","citationCount":"9","resultStr":"{\"title\":\"Divergent prognostic effects of pre-existing and treatment-emergent thyroid dysfunction in patients treated with immune checkpoint inhibitors.\",\"authors\":\"Mitchell S von Itzstein, Amrit S Gonugunta, Yiqing Wang, Thomas Sheffield, Rong Lu, Sadia Ali, Farjana J Fattah, Donglu Xie, Jennifer Cai, Yang Xie, David E Gerber\",\"doi\":\"10.1007/s00262-022-03151-2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Thyroid dysfunction is among the most common autoimmune diseases and immune checkpoint inhibitor (ICI)-induced immune-related adverse events (irAE). We determined the association between longitudinal thyroid function and clinical outcomes in patients treated with ICI.</p><p><strong>Methods: </strong>We identified all patients treated with ICI at UT Southwestern Medical Center from January 1, 2011, through December 31, 2020. We defined normal thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels according to institutional reference range. We defined clinical thyroid dysfunction using established criteria incorporating labs and treatment. We determined the association between thyroid function and overall survival (OS) using Kaplan-Meier curves, log-rank tests, and multivariate Cox proportional hazards model.</p><p><strong>Results: </strong>A total of 1781 patients were included in analyses, of whom 381 (21%) had abnormal baseline TSH. Patients with abnormal baseline TSH were more likely to be female, have kidney cancer, and initiate levothyroxine after ICI initiation (all P < 0.001). Patients with abnormal baseline TSH had inferior OS (median 16 vs 27 months; P < 0.001). Among patients with normal baseline TSH, those who had abnormal TSH after ICI initiation had improved OS (median 41 vs 22 months; P < 0.001). In a multivariate Cox model, abnormal baseline TSH was associated with worse OS (HR 1.62; 95% CI, 1.30-2.02; P < 0.001), while initiation of levothyroxine after ICI initiation was associated with improved OS (HR 0.62; 95% CI, 0.44-0.88; P = 0.008).</p><p><strong>Conclusions: </strong>ICI-induced thyroid dysfunction is associated with improved survival, although abnormal TSH prior to ICI initiation is associated with inferior survival.</p><p><strong>Precis: </strong>Thyroid abnormalities occur commonly in the general population and as immunotherapy toxicities. We found that immunotherapy-induced thyroid dysfunction is associated with better survival, but pre-existing thyroid abnormalities convey worse outcomes.</p>\",\"PeriodicalId\":520581,\"journal\":{\"name\":\"Cancer immunology, immunotherapy : CII\",\"volume\":\" \",\"pages\":\"2169-2181\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2022-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9308834/pdf/\",\"citationCount\":\"9\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer immunology, immunotherapy : CII\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00262-022-03151-2\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2022/1/24 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer immunology, immunotherapy : CII","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00262-022-03151-2","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/1/24 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
Divergent prognostic effects of pre-existing and treatment-emergent thyroid dysfunction in patients treated with immune checkpoint inhibitors.
Background: Thyroid dysfunction is among the most common autoimmune diseases and immune checkpoint inhibitor (ICI)-induced immune-related adverse events (irAE). We determined the association between longitudinal thyroid function and clinical outcomes in patients treated with ICI.
Methods: We identified all patients treated with ICI at UT Southwestern Medical Center from January 1, 2011, through December 31, 2020. We defined normal thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels according to institutional reference range. We defined clinical thyroid dysfunction using established criteria incorporating labs and treatment. We determined the association between thyroid function and overall survival (OS) using Kaplan-Meier curves, log-rank tests, and multivariate Cox proportional hazards model.
Results: A total of 1781 patients were included in analyses, of whom 381 (21%) had abnormal baseline TSH. Patients with abnormal baseline TSH were more likely to be female, have kidney cancer, and initiate levothyroxine after ICI initiation (all P < 0.001). Patients with abnormal baseline TSH had inferior OS (median 16 vs 27 months; P < 0.001). Among patients with normal baseline TSH, those who had abnormal TSH after ICI initiation had improved OS (median 41 vs 22 months; P < 0.001). In a multivariate Cox model, abnormal baseline TSH was associated with worse OS (HR 1.62; 95% CI, 1.30-2.02; P < 0.001), while initiation of levothyroxine after ICI initiation was associated with improved OS (HR 0.62; 95% CI, 0.44-0.88; P = 0.008).
Conclusions: ICI-induced thyroid dysfunction is associated with improved survival, although abnormal TSH prior to ICI initiation is associated with inferior survival.
Precis: Thyroid abnormalities occur commonly in the general population and as immunotherapy toxicities. We found that immunotherapy-induced thyroid dysfunction is associated with better survival, but pre-existing thyroid abnormalities convey worse outcomes.
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