{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T15:08:31Z","timestamp":1789139311552,"version":"build-2803163510"},"reference-count":29,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,10]],"date-time":"2022-02-10T00:00:00Z","timestamp":1644451200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Immune checkpoint inhibitors (CPI) are indicated for metastatic renal cell carcinoma (mRCC). Immune-related thyroiditis (irT), an immune-related adverse event (irAE), affects up to 30% of patients. We aimed to determine whether irT is associated with overall survival in mRCC. A retrospective cohort study of 123 consecutive patients treated with CPI for mRCC in a single center between 2015 and 2020 was conducted. Disease risk stratification was assessed by two methods: Heng criteria and a novel dichotomic stratification system to \u201cLow risk\u201d versus \u201cHigh risk\u201d adding number of metastatic sites. Thirty-eight percent of patients developed irT. In the general cohort, irT was not associated with a survival benefit. However, irT was associated with better survival in the poor risk group per Heng criteria (n = 17, HR = 0.25, p = 0.04) and in the novel \u201cHigh risk\u201d group (HR = 0.28, n = 42, p = 0.01), including after accounting for covariates in multivariate analysis (HR = 0.27, p = 0.003). Having any irAE was associated with improved survival in the whole cohort, with no significant correlation of any specific irAE, in either the whole cohort or the \u201cHigh risk\u201d group. We conclude that irT is an early and prevalent irAE, associated with prolonged survival in patients with poor\/\u201cHigh\u201d risk mRCC.<\/jats:p>","DOI":"10.3390\/cancers14040875","type":"journal-article","created":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T02:37:46Z","timestamp":1644547066000},"page":"875","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Immune-Related Thyroiditis as a Predictor for Survival in Metastatic Renal Cell Carcinoma"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7234-0256","authenticated-orcid":false,"given":"Shira","family":"Sagie","sequence":"first","affiliation":[{"name":"Institute of Oncology, Sheba Medical Center, Ramat Gan 52621, Israel"},{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"The Sheba Talpiot Medical Leadership Program, Sheba Medical Center, Ramat Gan 52621, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9832-9175","authenticated-orcid":false,"given":"Moran","family":"Gadot","sequence":"additional","affiliation":[{"name":"Institute of Oncology, Sheba Medical Center, Ramat Gan 52621, Israel"},{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meital","family":"Levartovsky","sequence":"additional","affiliation":[{"name":"Institute of Oncology, Sheba Medical Center, Ramat Gan 52621, Israel"},{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadas","family":"Gantz Sorotsky","sequence":"additional","affiliation":[{"name":"Institute of Oncology, Sheba Medical Center, Ramat Gan 52621, Israel"},{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raanan","family":"Berger","sequence":"additional","affiliation":[{"name":"Institute of Oncology, Sheba Medical Center, Ramat Gan 52621, Israel"},{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9603-3207","authenticated-orcid":false,"given":"Michal","family":"Sarfaty","sequence":"additional","affiliation":[{"name":"Institute of Oncology, Sheba Medical Center, Ramat Gan 52621, Israel"},{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Percik","sequence":"additional","affiliation":[{"name":"Institute of Oncology, Sheba Medical Center, Ramat Gan 52621, Israel"},{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"Division of Endocrinology, Diabetes and Metabolism, Sheba Medical Center, Ramat Gan 52621, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1056\/NEJMra1703481","article-title":"Immune-Related Adverse Events Associated with Immune Checkpoint Blockade","volume":"378","author":"Postow","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_2","unstructured":"Tran, J., and Ornstein, M.C. (2021). Clinical Review on the Management of Metastatic Renal Cell Carcinoma. JCO Oncol. Pract., OP-21."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5794","DOI":"10.1200\/JCO.2008.21.4809","article-title":"Prognostic Factors for Overall Survival in Patients With Metastatic Renal Cell Carcinoma Treated With Vascular Endothelial Growth Factor\u2013Targeted Agents: Results From a Large, Multicenter Study","volume":"27","author":"Heng","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/S1470-2045(12)70559-4","article-title":"External validation and comparison with other models of the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model: A population-based study","volume":"14","author":"Heng","year":"2013","journal-title":"Lancet Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4560","DOI":"10.1200\/JCO.2021.39.15_suppl.4560","article-title":"Analysis of the CLEAR study in patients (pts) with advanced renal cell carcinoma (RCC): Depth of response and efficacy for selected subgroups in the lenvatinib (LEN) + pembrolizumab (PEMBRO) and sunitinib (SUN) treatment arms","volume":"39","author":"Powles","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e679","DOI":"10.1634\/theoncologist.2019-0299","article-title":"Immune-Related Adverse Events by Immune Checkpoint Inhibitors Significantly Predict Durable Efficacy Even in Responders with Advanced Non-Small Cell Lung Cancer","volume":"25","author":"Akamatsu","year":"2020","journal-title":"Oncologist"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Paderi, A., Giorgione, R., Giommoni, E., Mela, M.M., Rossi, V., Doni, L., Minervini, A., Carini, M., Pillozzi, S., and Antonuzzo, L. (2021). Association between Immune Related Adverse Events and Outcome in Patients with Metastatic Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors. Cancers, 13.","DOI":"10.3390\/cancers13040860"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1089\/thy.2019.0250","article-title":"PD-L1 Inhibitor-Induced Thyroiditis Is Associated with Better Overall Survival in Cancer Patients","volume":"30","author":"Kotwal","year":"2020","journal-title":"Thyroid"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1089\/thy.2019.0726","article-title":"Overt Thyroid Dysfunction and Anti-Thyroid Antibodies Predict Response to Anti-PD-1 Immunotherapy in Cancer Patients","volume":"30","author":"Basak","year":"2020","journal-title":"Thyroid"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"36","DOI":"10.4158\/EP-2019-0244","article-title":"Thyroid Dysfunction, Recovery, and Prognosis in Melanoma Patients Treated with Immune Checkpoint Inhibitors: A Retrospective Review","volume":"26","author":"Guido","year":"2020","journal-title":"Endocr. Pract."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1007\/s12020-019-01871-7","article-title":"Thyroid dysfunction induced by nivolumab: Searching for disease patterns and outcomes","volume":"64","author":"Palmero","year":"2019","journal-title":"Endocrine"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1080\/0284186X.2021.1958006","article-title":"Thyroid dysfunction and survival in cancer patients treated with immune checkpoint inhibitors: Analyses from a large single tertiary cancer center database","volume":"60","author":"Percik","year":"2021","journal-title":"Acta Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1089\/thy.2020.0075","article-title":"Immune Checkpoint Inhibitor-Induced Thyroiditis Is Associated with Increased Intrathyroidal T Lymphocyte Subpopulations","volume":"30","author":"Kotwal","year":"2020","journal-title":"Thyroid"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.gendis.2017.11.002","article-title":"Unique cytologic features of thyroiditis caused by immune checkpoint inhibitor therapy for malignant melanoma","volume":"5","author":"Angell","year":"2018","journal-title":"Genes Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1007\/s12022-019-9579-2","article-title":"Pembrolizumab-Induced Thyroiditis","volume":"30","author":"Imblum","year":"2019","journal-title":"Endocr. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1210\/js.2017-00432","article-title":"Patients With Antithyroid Antibodies Are Prone To Develop Destructive Thyroiditis by Nivolumab: A Prospective Study","volume":"2","author":"Kobayashi","year":"2018","journal-title":"J. Endocr. Soc."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1007\/s40618-019-01058-x","article-title":"Low frequency of positive antithyroid antibodies is observed in patients with thyroid dysfunction related to immune check point inhibitors","volume":"42","author":"Mazarico","year":"2019","journal-title":"J. Endocrinol. Investig."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1016\/j.annonc.2021.05.357","article-title":"The positive effect of immune checkpoint inhibitor-induced thyroiditis on overall survival accounting for immortal time bias: A retrospective cohort study of 6596 patients","volume":"32","author":"Street","year":"2021","journal-title":"Ann. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e3704","DOI":"10.1210\/clinem\/dgab263","article-title":"Thyroid Immune-related Adverse Events Following Immune Checkpoint Inhibitor Treatment","volume":"106","author":"Muir","year":"2021","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1007\/s40618-017-0778-8","article-title":"Thyroid dysfunctions secondary to cancer immunotherapy","volume":"41","author":"Chalan","year":"2018","journal-title":"J. Endocrinol. Investig."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/sj.bjc.6604497","article-title":"The clinical implications of sunitinib-induced hypothyroidism: A prospective evaluation","volume":"99","author":"Wolter","year":"2008","journal-title":"Br. J. Cancer"},{"key":"ref_22","first-page":"163","article-title":"Paraneoplastic Syndromes in Urologic Malignancy: The Many Faces of Renal Cell Carcinoma","volume":"4","author":"Palapattu","year":"2002","journal-title":"Rev. Urol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5443","DOI":"10.1158\/1078-0432.CCR-11-0553","article-title":"Prognostic Model for Survival in Patients with Metastatic Renal Cell Carcinoma: Results from the International Kidney Cancer Working Group","volume":"17","author":"Manola","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1093\/annonc\/mdf257","article-title":"Prognostic factors of survival and rapid progression in782 patients with metastatic renal carcinomas treated by cytokines: A report from the Groupe Fran\u00e7ais d\u2019Immunoth\u00e9rapie","volume":"13","author":"Escudier","year":"2002","journal-title":"Ann. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1016\/S1470-2045(16)30196-6","article-title":"Active surveillance in metastatic renal-cell carcinoma: A prospective, phase 2 trial","volume":"17","author":"Rini","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/s41571-021-00564-3","article-title":"Tumour burden and efficacy of immune-checkpoint inhibitors","volume":"19","author":"Marabelle","year":"2022","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3762","DOI":"10.3389\/fimmu.2020.629722","article-title":"Tumor Burden and Immunotherapy: Impact on Immune Infiltration and Therapeutic Outcomes","volume":"11","author":"Kim","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1186\/s12885-019-6073-7","article-title":"Sites of metastasis and association with clinical outcome in advanced stage cancer patients treated with immunotherapy","volume":"19","author":"Bilen","year":"2019","journal-title":"BMC Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Paderi, A., Gambale, E., Botteri, C., Giorgione, R., Lavacchi, D., Brugia, M., Mazzoni, F., Giommoni, E., Bormioli, S., and Amedei, A. (2021). Association of Systemic Steroid Treatment and Outcome in Patients Treated with Immune Checkpoint Inhibitors: A Real-World Analysis. Molecules, 26.","DOI":"10.3390\/molecules26195789"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/4\/875\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:17:29Z","timestamp":1760134649000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/4\/875"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,10]]},"references-count":29,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["cancers14040875"],"URL":"https:\/\/doi.org\/10.3390\/cancers14040875","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,10]]}}}