{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T06:19:52Z","timestamp":1783664392450,"version":"3.55.0"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,12]],"date-time":"2021-07-12T00:00:00Z","timestamp":1626048000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Thyroid dysfunction is common for cancer patients receiving PD-1\/PD-L1 inhibitor therapies. To clarify the incidence risk of thyroid dysfunction would be important for guiding anti-PD-1 and anti-PD-L1 immunotherapy. Therefore, the updated meta-analysis was conducted to evaluate the incidence risk of thyroid dysfunction caused by PD-1\/PD-L1 inhibitors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>PD-1\/PD-L1 inhibitor related clinical trials were collected by a systematic search of the PubMed. Some relevant studies were identified by a manual search. The incidence risk of all grades and grades 3-5 was analyzed and evaluated by random effect\u00a0model. The Newcastle Ottawa Scale was used for the quality assessment of all clinical trials.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Forty-three clinical trials were collected. Compared with chemotherapy, the risk of hypothyroidism of all grades was significantly higher (OR=7.15, 95%CI:[4.85, 10.55], I<jats:sup>2<\/jats:sup>\u00a0= 40%, Z=9.91(<jats:italic>P &amp;lt;<\/jats:italic>0.00001)) in PD-1\/PD-L1 group. Similar results could also be noted, when the control group was placebo or CTLA-4. When PD-1\/PD-L1 was combined with other treatments for cancer patients, the risk of hypothyroidism of all grades was also significantly increased. Similar to the analysis results of hypothyroidism, PD-1\/PD-L1 inhibitors played the same role in increasing the risk of hyperthyroidism and thyroiditis. Few significant analysis results was noted, when the risk of thyroid dysfunction of grades 3-5 was assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Whether used alone or in combination with other anti-tumor drugs, PD-1\/PD-L1 inhibitors increased the risk of thyroid dysfunction, especially for hypothyroidism. Furthermore, PD-1\/PD-L1 was better than chemotherapy and CTLA-4 in increasing the risk of thyroid dysfunction.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2021.667650","type":"journal-article","created":{"date-parts":[[2021,7,12]],"date-time":"2021-07-12T12:15:59Z","timestamp":1626092159000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["The Risk of Immune-Related Thyroid Dysfunction Induced by PD-1\/PD-L1 Inhibitors in Cancer Patients: An Updated Systematic Review and Meta-Analysis"],"prefix":"10.3389","volume":"11","author":[{"given":"Yuan","family":"Tian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxiao","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiqin","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guohai","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuping","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"86","DOI":"10.3322\/caac.21596","article-title":"A Review of Cancer Immunotherapy Toxicity","volume":"70","author":"Kennedy","year":"2020","journal-title":"CA Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2018.0047","article-title":"New NCCN Guidelines: Recognition and Management of Immunotherapy-Related Toxicity","volume":"16","author":"Thompson","year":"2018","journal-title":"J Natl Compr Canc Netw"},{"key":"B3","doi-asserted-by":"publisher","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":"B4","first-page":"S1470","article-title":"Camrelizumab Versus Investigator\u2019s Choice of Chemotherapy as Second-Line Therapy for Advanced or Metastatic Oesophageal Squamous Cell Carcinoma (ESCORT): A Multicentre, Randomised, Open-Label, Phase 3 Study [Published Online Ahead of Print, 2020 May 13]","author":"Huang","year":"2020","journal-title":"Lancet Oncol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2002788","article-title":"Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma","volume":"383","author":"Powles","year":"2020","journal-title":"N Engl J Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30417-7","article-title":"Adjuvant Nivolumab Plus Ipilimumab or Nivolumab Monotherapy Versus Placebo in Patients With Resected Stage IV Melanoma With No Evidence of Disease (IMMUNED): A Randomised, Double-Blind, Placebo-Controlled, Phase 2 Trial","volume":"395","author":"Zimmer","year":"2020","journal-title":"Lancet"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1910549","article-title":"KEYNOTE-522 Investigators. 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