Department of Rheumatology and Immunology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Department of Endocrinology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Front Immunol. 2024 May 7;15:1381061. doi: 10.3389/fimmu.2024.1381061. eCollection 2024.
Thyroid immune-related adverse events (irAEs) associated with immune checkpoint inhibitor (ICI) treatment appear to correlate with a better prognosis. We aimed to investigate clinical biomarkers associated with thyroid irAEs.
We retrospectively analyzed data from 129 patients receiving programmed cell death protein 1 (PD-1) inhibitors for stage III and IV gastrointestinal tumors. Patients were divided into two groups: "thyroid irAEs" group and "no thyroid irAEs" group. We compared continuous variables using Mann-Whitney U and Kruskal-Wallis tests and categorical variables using Pearson's chi-square test. Survival curves were generated using the Kaplan-Meier method, and associations between clinical features and thyroid irAEs were assessed using univariate and multivariate logistic regression models. Associations for thyroid irAEs and outcomes [progression-free survival (PFS), overall survival (OS)] of the patients were performed with a Cox proportional hazard model.
A total of 129 patients, including 66 gastric cancer, 30 esophageal squamous cell carcinoma, and 33 hepatocellular carcinoma (HCC), were involved in this analysis with 47 cases of thyroid irAEs occurrence. The Cox proportional hazard model analysis confirmed the extended PFS [hazard rate (HR) = 0.447, 95% confidence interval (CI): 0.215 to 0.931, = 0.031] and OS (HR = 0.424, 95% CI: 0.201 to 0.893, = 0.024) for thyroid irAEs group when compared with those of the no thyroid irAEs group. Association between thyroid irAEs and clinical characteristics at baseline was analyzed subsequently by univariate analysis. Higher body mass index ( = 0.005), increased eosinophil count ( = 0.014), increased lactate dehydrogenase ( = 0.008), higher baseline thyroid stimulating hormone (TSH) ( = 0.001), HCC ( = 0.001) and increased adenosine deaminase (ADA) ( = 0.001) were linked with thyroid irAEs occurrence. The multivariable logistic regression model indicated that ADA [odds rate (OR) = 4.756, 95% CI: 1.147 to 19.729, = 0.032] was independently associated with thyroid irAEs occurrence.
Increased baseline level of ADA was associated with thyroid irAEs occurrence in patients with advanced gastrointestinal tumors who received ICI treatment. In the case of abnormal ADA, attention should be paid to the risk of thyroid irAEs.
与免疫检查点抑制剂（ICI）治疗相关的甲状腺免疫相关不良事件（irAEs）似乎与更好的预后相关。我们旨在研究与甲状腺 irAEs 相关的临床生物标志物。
我们回顾性分析了 129 名接受程序性死亡蛋白 1（PD-1）抑制剂治疗 III 期和 IV 期胃肠道肿瘤的患者数据。患者分为两组：“甲状腺 irAEs”组和“无甲状腺 irAEs”组。我们使用 Mann-Whitney U 和 Kruskal-Wallis 检验比较连续变量，使用 Pearson's chi-square 检验比较分类变量。使用 Kaplan-Meier 方法生成生存曲线，并使用单变量和多变量逻辑回归模型评估临床特征与甲状腺 irAEs 之间的关联。使用 Cox 比例风险模型对甲状腺 irAEs 与患者的无进展生存期（PFS）和总生存期（OS）进行关联分析。
本分析共纳入 129 名患者，包括 66 名胃癌、30 名食管鳞状细胞癌和 33 名肝细胞癌（HCC）患者，其中 47 例发生甲状腺 irAEs。Cox 比例风险模型分析证实，与无甲状腺 irAEs 组相比，甲状腺 irAEs 组的 PFS（风险比[HR] = 0.447，95%置信区间[CI]：0.215 至 0.931， = 0.031）和 OS（HR = 0.424，95% CI：0.201 至 0.893， = 0.024）均延长。随后通过单变量分析对甲状腺 irAEs 与基线临床特征之间的关联进行了分析。更高的体重指数（ = 0.005）、嗜酸性粒细胞计数增加（ = 0.014）、乳酸脱氢酶升高（ = 0.008）、较高的基线促甲状腺激素（TSH）（ = 0.001）、HCC（ = 0.001）和升高的腺苷脱氨酶（ADA）（ = 0.001）与甲状腺 irAEs 发生相关。多变量逻辑回归模型表明，ADA（比值比[OR] = 4.756，95%CI：1.147 至 19.729， = 0.032）与甲状腺 irAEs 的发生独立相关。
在接受 ICI 治疗的晚期胃肠道肿瘤患者中，基线 ADA 水平升高与甲状腺 irAEs 的发生相关。在 ADA 异常的情况下，应注意甲状腺 irAEs 的风险。
