{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T23:27:20Z","timestamp":1773185240692,"version":"3.50.1"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T00:00:00Z","timestamp":1736985600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017610","name":"Shenzhen Science and Technology Innovation Program","doi-asserted-by":"publisher","award":["JCYJ2021032411261103"],"award-info":[{"award-number":["JCYJ2021032411261103"]}],"id":[{"id":"10.13039\/501100017610","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Immunotherapy represents a major breakthrough in malignant tumor treatment in recent years. Anti-PD-1 immunotherapy has significantly prolonged Event-free Survival (EFS) in Nasopharyngeal Carcinoma (NPC). However, its potent anti-tumor effects can also attack normal tissues and organs, leading to immune-related adverse effects (irAE), with the thyroid being one of the most commonly affected organs. This study aims to analyze the incidence and related factors of thyroid dysfunction in NPC patients receiving anti-PD-1 immunotherapy with\/without Intensity-modulated radiotherapy (IMRT), and further explore whether radiotherapy interacts with thyroid immune-related adverse reactions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>108 NPC patients receiving immunotherapy combined with chemotherapy or chemoradiotherapy were retrospectively included. Data collected included smoking status, BMI, presence of thyroid nodules, staging, treatment modality, thyroid mean dose (Dmean), percentage of thyroid volume receiving more than x Gy, pituitary mean dose (Dmean), and TSH and FT4 levels per cycle. T-tests, rank-sum tests, multivariate logistic regression analysis, ROC curves, and Cox proportional hazards models were used to evaluate the effects of anti-PD-1 immunotherapy combined with chemoradiotherapy on thyroid function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patients with pre-treatment smoking history, thyroid nodules, and cervical lymph node metastasis were more likely to develop thyroid dysfunction (P&amp;lt;0.05). During treatment, 81 patients developed varying degrees of thyroid dysfunction. Subclinical hyperthyroidism (33.9%) was most common in the immunotherapy plus chemoradiotherapy group, while subclinical hypothyroidism (23.9%) was most common in the immunotherapy plus chemotherapy group. Compared to the immunotherapy plus chemotherapy group, the immunotherapy plus chemoradiotherapy group showed higher incidence and severity of hyperthyroidism (median peak FT4 concentration: 19.11 pmol\/L vs 16.21 pmol\/L) (P=0.001). The immunotherapy plus chemoradiotherapy group showed lower incidence but increased severity of hypothyroidism compared to the immunotherapy plus chemotherapy group, though these differences were not statistically significant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>NPC patients with smoking history, thyroid nodules, and cervical lymph node metastasis have significantly increased risk of thyroid dysfunction when receiving anti-PD-1 immunotherapy combined with IMRT. The combination of anti-PD-1 immunotherapy and IMRT increases both the incidence and severity of thyroid dysfunction.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1495946","type":"journal-article","created":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T06:11:06Z","timestamp":1737007866000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Evaluating the influence of anti-PD-1 immunotherapy combined with IMRT on thyroid dysfunction in nasopharyngeal carcinoma"],"prefix":"10.3389","volume":"15","author":[{"given":"Liqianqi","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zihuang","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianming","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shihai","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Long","family":"Gong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shanyi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yucong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,1,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA A Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1905287","article-title":"Gemcitabine and cisplatin induction chemotherapy in nasopharyngeal carcinoma","volume":"381","author":"Zhang","year":"2019","journal-title":"N Engl J Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.12.007","article-title":"Nasopharyngeal carcinoma: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up\u2020","volume":"32","author":"Bossi","year":"2021","journal-title":"Ann Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2022.0016","article-title":"NCCN guidelines\u00ae Insights: head and neck cancers, version 1.2022","volume":"20","author":"Caudell","year":"2022","journal-title":"J Natl Compr Canc Netw"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)00594-4","article-title":"Induction-concurrent chemoradiotherapy with or without sintilimab in patients with locoregionally advanced nasopharyngeal carcinoma in China (CONTINUUM): a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial","volume":"403","author":"Liu","year":"2024","journal-title":"Lancet"},{"key":"B6","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1001\/jamaoncol.2017.3064","article-title":"Incidence of endocrine dysfunction following the use of different immune checkpoint inhibitor regimens: A systematic review and meta-analysis","volume":"4","author":"Barroso-Sousa","year":"2018","journal-title":"JAMA Oncol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2017.03.007","article-title":"Thyroid V40 predicts primary hypothyroidism after intensity modulated radiation therapy for nasopharyngeal carcinoma","volume":"98","author":"Sommat","year":"2017","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.radonc.2011.03.002","article-title":"Radiation-induced hypothyroidism in head and neck cancer patients: a systematic review","volume":"99","author":"Boomsma","year":"2011","journal-title":"Radiother Oncol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3325\/cmj.2008.4.515","article-title":"Genome damage in oropharyngeal cancer patients treated by radiotherapy","volume":"49","author":"Gamulin","year":"2008","journal-title":"Croat Med J"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-05-0179","article-title":"Angiogenesis and tumor growth inhibition by a matrix metalloproteinase inhibitor targeting radiation-induced invasion","volume":"4","author":"Kaliski","year":"2005","journal-title":"Mol Cancer Ther"},{"key":"B11","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1038\/emm.2005.3","article-title":"NF-\u03baB decoy potentiates the effects of radiation on vascular smooth muscle cells by enhancing apoptosis","volume":"37","author":"Zhang","year":"2005","journal-title":"Exp Mol Med"},{"key":"B12","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.radonc.2017.10.032","article-title":"International guideline for the delineation of the clinical target volumes (CTV) for nasopharyngeal carcinoma","volume":"126","author":"Lee","year":"2018","journal-title":"Radiother Oncol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.adro.2019.08.006","article-title":"Radiation-induced hypothyroidism after radical intensity modulated radiation therapy for oropharyngeal carcinoma","volume":"5","author":"Kamal","year":"2020","journal-title":"Adv Radiat Oncol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"338","DOI":"10.3390\/cancers13020338","article-title":"Recent advances and future directions in clinical management of head and neck squamous cell carcinoma","volume":"13","author":"Muzaffar","year":"2021","journal-title":"Cancers (Basel)"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2012-0483","article-title":"Ipilimumab and its toxicities: a multidisciplinary approach","volume":"18","author":"Fecher","year":"2013","journal-title":"Oncologist"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.01992","article-title":"Management of immune-related adverse events in patients treated with chimeric antigen receptor T-cell therapy: ASCO guideline","volume":"39","author":"Santomasso","year":"2021","journal-title":"J Clin Oncol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/hed.v36.11","article-title":"Hypothyroidism after 3-dimensional conformal radiotherapy and intensity-modulated radiotherapy for head and neck cancers: prospective data from 2 randomized controlled trials","volume":"36","author":"Murthy","year":"2014","journal-title":"Head Neck"},{"key":"B18","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1186\/s13014-020-01490-x","article-title":"Thyroid V50 is a risk factor for hypothyroidism in patients with nasopharyngeal carcinoma treated with intensity-modulated radiation therapy: a retrospective study","volume":"15","author":"Zhou","year":"2020","journal-title":"Radiat Oncol"},{"key":"B19","doi-asserted-by":"publisher","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":"B20","doi-asserted-by":"publisher","DOI":"10.4103\/ijc.IJC_946_19","article-title":"Radiation-induced hypothyroidism in patients of oral squamous cell carcinoma: A retrospective analysis of 195 patients","volume":"59","author":"Jain","year":"2022","journal-title":"Indian J Cancer"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.29271\/jcpsp.2021.03.359","article-title":"Relation of External Beam Radiotherapy Dose with Subclinical Hypothyroidism in Patients undergoing Adjuvant Neck Radiation after Surgery for Squamous Cell Carcinoma of Head and Neck","volume":"31","author":"Uddin","year":"2021","journal-title":"J Coll Physicians Surg Pak"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.26914\/c.cnkihy.2023.017635","article-title":"Research status of hypothyroidism after breast cancer surgery and radiationtherapy","volume":"29","author":"Huang &","year":"2020","journal-title":"Chin J Radiat Oncol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.v8.16","article-title":"Thyroid dose-volume thresholds for the risk of radiation-related hypothyroidism in nasopharyngeal carcinoma treated with intensity-modulated radiotherapy-A single-institution study","volume":"8","author":"Huang","year":"2019","journal-title":"Cancer Med"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1002\/hed.20847","article-title":"Hypopituitarism after radiotherapy for extracranial head and neck cancers","volume":"30","author":"Bhandare","year":"2008","journal-title":"Head Neck"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2013.06.029","article-title":"Hypothyroidism after primary radiotherapy for head and neck squamous cell carcinoma: normal tissue complication probability modeling with latent time correction","volume":"109","author":"R\u00f8njom","year":"2013","journal-title":"Radiother Oncol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"104444","DOI":"10.1016\/j.oraloncology.2019.104444","article-title":"Radiation induced hypothyroidism - Why is early intervention necessary","volume":"103","author":"Aggarwal","year":"2020","journal-title":"Oral Oncol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/S0360-3016(00)01373-0","article-title":"Long-term complications of total body irradiation in adults","volume":"49","author":"Thomas","year":"2001","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.3390\/cancers15041063","article-title":"FDG-PET\/CT in the monitoring of lymphoma immunotherapy response: current status and future prospects","volume":"15","author":"Al-Ibraheem","year":"2023","journal-title":"Cancers"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1495946\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T06:11:09Z","timestamp":1737007869000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1495946\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,16]]},"references-count":28,"alternative-id":["10.3389\/fimmu.2024.1495946"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1495946","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,16]]},"article-number":"1495946"}}