免疫检查点抑制剂引起的甲状腺功能减退在日本受试者中预示着治疗反应。
Immune checkpoint inhibitor-induced hypothyroidism predicts treatment response in Japanese subjects.
发表日期：2023
作者：
Yuichiro Iwamoto, Tomohiko Kimura, Kazunori Dan, Mana Ohnishi, Haruka Takenouchi, Hideyuki Iwamoto, Junpei Sanada, Yoshiro Fushimi, Yukino Katakura, Masashi Shimoda, Shuhei Nakanishi, Tomoatsu Mune, Kohei Kaku, Hideaki Kaneto
来源：
Frontiers in Endocrinology
摘要：
免疫检查点抑制剂（ICIs）会导致各种免疫相关的不良事件（irAEs）。其中，甲状腺功能异常是最常见的。患有irAEs的患者的生存率比没有irAEs的患者要高，但目前还无法确定甲状腺功能异常的程度是否与ICIs治疗的反应或生存率相关。
本研究是一项单中心、回顾性、观察性研究。研究纳入了2014年9月1日至2022年5月31日期间在川崎医学院医院接受ICIs治疗的466名患者，并评估了ICIs治疗后甲状腺功能异常的程度及生存和缓解率。TSH小于10 μIU/mL的原发性甲状腺功能减退被归类为一级，TSH大于10 μIU/mL或需要服用左甲状腺素的原发性甲状腺功能减退被归类为二至四级。
研究参与者的平均年龄为68.2 ± 10.3岁，男性参与者的比例为72.6%。研究参与者中ICIs诱导的甲状腺功能异常的发生率为28.2%。与NTF组相比，在接受ICIs治疗时，一级和二至四级的TSH水平显著升高（p<0.0001）。ICI治疗后1年的生存率在一级组为64.9%，二至四级组为88.9%，而NTF组为52.1%（p<0.0001）。ICI治疗时的肿瘤分期在各组间没有差异（p=0.68）。然而，按照RECIST标准评估的缓解率在二至四级组中显著高于NTF组（p<0.0001）。
ICI诱导的甲状腺功能异常与生存率、观察时间平均值和治疗缓解率显著相关。在接受ICIs治疗的患者中定期监测甲状腺激素水平非常重要。
版权所有 © 2023 Iwamoto, Kimura, Dan, Ohnishi, Takenouchi, Iwamoto, Sanada, Fushimi, Katakura, Shimoda, Nakanishi, Mune, Kaku and Kaneto.
Immune checkpoint inhibitors (ICIs) cause a variety of immune-related adverse events (irAEs). Among them, thyroid dysfunction is most frequently observed. Patients with irAEs have higher survival rates than those without irAEs, but there is no certainty as to whether the degree of thyroid dysfunction is associated with treatment response or survival with ICIs.This is a single-center, retrospective, observational study. The study included 466 patients who received ICI at Kawasaki Medical School Hospital from September 1, 2014, to May 31, 2022 and evaluated the degree of abnormal thyroid function and survival and remission rates after treatment with ICIs. Primary hypothyroidism of less than 10 μIU/mL TSH was classified as grade 1, and primary hypothyroidism requiring more than 10 μIU/mL TSH or levothyroxine as grade 2-4.The mean age of the study participants was 68.2 ± 10.3 years, and the percentage of male participants was 72.6%. The frequency of ICI-induced thyroid dysfunction in the study participants was 28.2%. TSH levels were significantly higher in Grade 1 and Grades 2-4 when treated with ICI compared to NTF (p<0.0001). The survival rate at 1 year after ICI administration was significantly higher with 64.9% for grade 1 and 88.9% for grades 2-4 compared to 52.1% for NTF (p<0.0001). Cancer stage at the time of ICI administration did not differ among the groups (p=0.68). Nevertheless, the remission rate assessed by RECIST criteria was significantly higher in grades 2-4 compared to NTF (p<0.0001).ICI-induced thyroid dysfunction was significantly correlated with survival, mean observation time, and treatment remission rate. It is important to monitor thyroid hormone levels regularly in patients receiving ICIs.Copyright © 2023 Iwamoto, Kimura, Dan, Ohnishi, Takenouchi, Iwamoto, Sanada, Fushimi, Katakura, Shimoda, Nakanishi, Mune, Kaku and Kaneto.