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癌症免疫治疗期间甲状腺不良事件的预测因素:单中心真实世界经验。

Predictors of thyroid adverse events during cancer immunotherapy: a real-life experience at a single center.

机构信息

Endocrinology Unit, Department of Human Pathology of Adulthood and Childhood DETEV "G. Barresi", University of Messina, Messina, Italy.

Medical Oncology Unit, Department of Human Pathology of Adulthood and Childhood DETEV "G. Barresi", University of Messina, Messina, Italy.

出版信息

J Endocrinol Invest. 2023 Nov;46(11):2399-2409. doi: 10.1007/s40618-023-02096-2. Epub 2023 Apr 20.

Abstract

BACKGROUND

Thyroid dysfunction is among the most common immune-related adverse events (irAEs) of immune checkpoint inhibitors (ICIs) therapy. Data regarding potential predictors of the development of thyroid irAEs are still limited and sometimes conflicting.

PATIENTS AND METHODS

We assessed potential risk factors and clinical outcomes associated with the onset of thyroid irAEs in a cohort of patients with different types of cancer treated with ICIs at a single center. Clinical and biochemical data, including thyroid function tests and autoantibodies at baseline and during treatment, were collected, and the onset of thyroid irAEs was recorded. Patients with thyroid dysfunction and/or under levothyroxine therapy before starting ICI were excluded.

RESULTS

110 patients (80 M, 30 F, aged 32-85 years; 56.4% non-small-cell lung cancer, 87% treated with anti-PD-1) with complete information were included in the study. Among them, 32 (29%) developed thyroid irAEs during ICIs therapy. Primary hypothyroidism was the most common irAEs, occurring in 31 patients (28.18% of the whole cohort), including 14 patients who experienced a transient thyrotoxicosis. About 60% of irAEs occurred within the first 8 weeks of therapy. At multivariate analysis, anti-thyroid autoantibodies positivity at baseline (OR 18.471, p = 0.022), a pre-existing (autoimmune and non-autoimmune) thyroid disorder (OR 16.307, p < 0.001), and a family history of thyroid diseases (OR = 9.287, p = 0.002) were independent predictors of the development of thyroid irAEs.

CONCLUSION

Our data confirm the high frequency of thyroid dysfunctions (mostly hypothyroidism) during ICIs, and provide data on valuable predictors of thyroid toxicities that may help clinicians in identifying patients at risk for developing irAEs.

摘要

背景

甲状腺功能障碍是免疫检查点抑制剂 (ICI) 治疗中最常见的免疫相关不良事件 (irAE) 之一。关于甲状腺 irAE 发展的潜在预测因素的数据仍然有限,有时甚至相互矛盾。

方法

我们评估了单中心治疗的不同类型癌症患者接受 ICI 治疗时发生甲状腺 irAE 的潜在危险因素和临床结局。收集了包括甲状腺功能检查和自身抗体在内的临床和生化数据,记录了甲状腺 irAE 的发病情况。排除了在开始 ICI 之前有甲状腺功能障碍和/或正在接受左甲状腺素治疗的患者。

结果

110 名患者(80 名男性,30 名女性,年龄 32-85 岁;56.4%非小细胞肺癌,87%接受抗 PD-1 治疗)的信息完整,包括在内。其中 32 名(29%)在 ICI 治疗期间发生甲状腺 irAE。原发性甲状腺功能减退症是最常见的 irAE,发生在 31 名患者中(整个队列的 28.18%),包括 14 名经历短暂甲状腺毒症的患者。约 60%的 irAE 发生在治疗的前 8 周内。多变量分析显示,基线时抗甲状腺自身抗体阳性(OR 18.471,p=0.022)、存在(自身免疫和非自身免疫)甲状腺疾病(OR 16.307,p<0.001)和甲状腺疾病家族史(OR=9.287,p=0.002)是甲状腺 irAE 发生的独立预测因素。

结论

我们的数据证实了 ICI 期间甲状腺功能障碍(主要是甲状腺功能减退症)的高频率,并提供了有关甲状腺毒性的有价值预测因素的数据,这可能有助于临床医生识别发生 irAE 的风险患者。

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