程序性死亡受体1抑制剂对恶性实体瘤患者甲状腺功能的影响  

Influence of programmed cell death-1 inhibitors on thyroid function of patients with malignant solid tumors

作　　者：冯涵 崔抗[1] 耿一萌 李新 孟轲 马望[1] FENG Han;CUI Kang;GENG Yi-meng;LI Xin;MENG Ke;MA Wang(Department of Oncology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou Henan 450052,China)

机构地区：[1]郑州大学第一附属医院肿瘤科,河南郑州450052

出　　处：《中华实用诊断与治疗杂志》2022年第4期362-364,共3页Journal of Chinese Practical Diagnosis and Therapy

基　　金：国家自然科学基金项目(82073168)。

摘　　要：目的 观察恶性实体瘤患者采用程序性死亡受体1(programmed cell death-1, PD-1)抑制剂治疗后甲状腺功能变化,探讨其发生甲状腺功能异常的危险因素。方法 恶性实体瘤患者146例,均采用PD-1抑制剂治疗,按照标准剂量2 mg/(kg·d)治疗,3周为1个疗程,治疗2个疗程后采用电化学发光法检测患者甲状腺相关激素水平,根据甲状腺功能分为甲状腺功能正常组89例,甲状腺功能异常组57例(亚临床/临床甲状腺功能减退症或亢进)。比较2组年龄、性别比例、KPS评分、肿瘤类型、手术史、放疗史、化疗史、治疗方式、治疗方案、靶向治疗史等临床资料;采用多因素logistic回归分析恶性实体瘤患者采用PD-1抑制剂治疗后发生甲状腺功能异常的影响因素。结果 146例恶性实体瘤患者PD-1抑制剂治疗后甲状腺功能异常57例,发生率为39.04%,其中甲状腺功能减退44例(30.14%),甲状腺功能亢进13例(8.90%)。甲状腺功能异常组有化疗史(68.42%)、治疗方式三线以上(40.35%)、联合抗血管生成治疗(66.67%)比率均高于甲状腺功能正常组(44.94%、14.61%、35.96%)(P<0.05)。治疗方式三线以上(OR=3.95,95%CI:1.20~13.02,P=0.024)、联合抗血管生成治疗(OR=3.42,95%CI:1.09~10.75,P=0.036)是恶性实体瘤患者采用PD-1抑制剂治疗后发生甲状腺功能异常的危险因素。结论 采用三线以上治疗方式及联合抗血管生成治疗的恶性实体瘤患者采用PD-1抑制剂治疗后易发生甲状腺功能异常。Objective To observe the changes of thyroid function of patients with malignant solid tumors after programmed cell death-1(PD-1) inhibitors therapy, and to explore the risk factors of thyroid dysfunction. Methods Totally 146 patients with malignant solid tumors received PD-1 inhibitors therapy at a standard dose [2 mg/(kg·d)] for 3 weeks as 1 course. After 2 courses, the levels of thyroid hormone were detected by electrochemiluminescence. According to thyroid function, 146 patients were divided into 89 patients with normal thyroid function(normal thyroid function group) and 57 patients with subclinical/clinical hypothyroidism or hyperthyroidism(abnormal thyroid function group). The clinical data were compared between two groups, including age, gender ratio, KPS score, pathological type, history of surgery, history of radiotherapy, history of chemotherapy, treatment method, treatment plan and history of targeted therapy. Multivariate logistic regression analysis was performed to analyze the influencing factors of thyroid dysfunction in patients with malignant solid tumors after PD-1 inhibitors therapy. Results Among 146 patients, 57 patients developed abnormal thyroid function after PD-1 inhibitors therapy, with an incidence of 39.04%, including 44 patients with hypothyroidism(30.14%) and 13 patients with hyperthyroidism(8.9%). The percentages of patients with chemotherapy history, third-or later-line therapy and combined anti-angiogenesis therapy were higher in abnormal thyroid function group(68.42%, 40.35%, 66.67%) than those in normal thyroid function group(44.94%, 14.61%, 35.96%)(P<0.05). The third-or later-line therapy(OR=3.95, 95%CI: 1.20-13.02, P=0.024), and combined anti-angiogenesis therapy(OR=3.42, 95%CI: 1.09-10.75, P=0.036) were the risk factors of thyroid dysfunction after PD-1 inhibitors therapy in patients with malignant solid tumors. Conclusion The patients with malignant solid tumors are more likely to develop thyroid dysfunction after third-or later-line therapy and combined anti-angiogenesis th

关 键 词：恶性实体瘤 程序性死亡受体1 免疫相关不良事件 甲状腺功能 抗血管生成治疗 

分 类 号：R730.5[医药卫生—肿瘤]