PD-1/PD-L1抑制剂诱发免疫相关甲状腺功能障碍的影响因素及肿瘤总生存期分析  

Influencing factors of immune-related thyroid dysfunction and overall survival in cancer patients treated with PD-1/PD-L1 inhibitors

作　　者：雷凤萍 姚涓川 马婷 李海琛 崔巍[1] LEI Fengping;YAO Juanchuan;MA Ting;LI Haichen;CUI Wei(Department of Geriatric Endocrinology,The First Hospital of Xi’an Jiaotong University,Xi’an 710061;Department of Geriatric Endocrinology,the Ninth Hospital of Xi’an,Xi’an 710054,China)

机构地区：[1]西安交通大学第一附属医院老年内分泌科,陕西西安710061 [2]西安市第九医院内分泌科,陕西西安710054

出　　处：《西安交通大学学报（医学版）》2024年第6期967-974,共8页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：陕西省高校联合项目(No.2020GXLH-Y-029);西安交通大学医学“基础-临床”融合创新项目(No.YXJLRH2022018)。

摘　　要：目的探究程序性死亡受体-1(PD-1)/程序性死亡配体-1(PD-L1)抑制剂诱发免疫相关甲状腺功能障碍(irTD)的影响因素及对肿瘤总生存期(OS)的影响。方法纳入211例PD-1/PD-L1抑制剂治疗的肿瘤患者,比较是否发生irTD组间的差异,并进行亚组分析。采用多因素Logistic回归分析探究irTD的影响因素,生存分析法探究是否发生irTD与OS的关系,组间比较采用log-rank检验,多模型COX回归分析评估irTD对OS的影响。结果irTD的发生率为26.1%,1级发生率13.3%,2级发生率10.0%,3~4级发生率2.8%,发生的中位时间为第9周(IQR:5~25周)。性别、吸烟史、靶向史、基线甲状腺抗体在是否发生irTD组间具有统计学差异(P<0.05)。irTD患者甲状腺球蛋白抗体(TGAb)在第3周开始升高,第6~30周高于基线水平,30周后开始下降并逐渐恢复至基线水平,甲状腺微粒体抗体(TMAb)的变化幅度小于TGAb。亚组分析显示,甲亢组首次接受免疫治疗的年龄较甲减组小(P<0.05),基线促甲状腺激素(TSH)水平低于甲减组(P<0.05)。多因素Logistic回归分析显示,基线甲状腺抗体阳性的患者发生irTD的风险是阴性患者的4.595倍(95%CI:2.286~9.239,P<0.001)。生存分析显示,irTD患者的OS更长。多模型COX回归分析显示:在调整年龄、性别、化疗、肿瘤类型、是否转移等因素后irTD患者的OS更长(HR=0.228,95%CI:0.079~0.656,P=0.006)。结论irTD严重程度以1~2级为主,3~4级少见。基线甲状腺抗体阳性是irTD发生的独立危险因素。发生irTD的患者具有更长的OS,可能是由于irTD患者具有更好的免疫应答。Objective To investigate the influencing factors of immune-related thyroid dysfunction(irTD)treated with programmed death-1(PD-1)/programmed death ligand-1(PD-L1)inhibitors and their impact on overall survival(OS)of cancer.Methods We enrolled 211 cancer patients treated with PD-1/PD-L1 inhibitors.Clinical differences between irTD groups were compared,and subgroup analysis was performed.Multifactor Logistic regression analysis was used to identify influencing factors of irTD,while survival analysis was used to explore the relationship between the occurrence of irTD and OS,and the log-rank test was used for comparison between groups.The multi-model COX regression analysis was used to evaluate the impact of irTD on OS.Results The incidence rate of irTD was 26.1%,with 13.3%,10.0%and 2.8%,respectively for grade 1,grade 2,and grades 3-4,and the median time of occurrence was at week 9(IQR:5-25 weeks).Significant differences were observed between the irTD and non-irTD groups in terms of gender,smoking history,targeted therapy history,and baseline thyroid antibody status(P<0.05).In irTD patients,thyroglobulin antibody(TGAb)levels began to increase from week 3,remained above the baseline from week 6 to week 30,and then gradually declined to the baseline level after week 30.The change in thyroid microsomal antibody(TMAb)levels was less pronounced than that of TGAb.Subgroup analysis showed that patients with hyperthyroidism were younger at the time of initial immunotherapy than those with hypothyroidism(P<0.05)and had lower baseline TSH levels(P<0.05).Multifactor Logistic regression analysis revealed that patients with positive baseline thyroid antibodies had a 4.595-fold higher risk of developing irTD compared to those with negative antibodies(95%CI:2.286-9.239,P<0.001).Survival analysis revealed that patients with irTD had a longer OS and the multi-model COX regression analysis revealed that after adjusting for factors such as age,gender,chemotherapy,tumor type and tumor metastasis status,patients with irTD had a significa

关 键 词：程序性死亡受体-1(PD-1)/程序性死亡配体-1(PD-L1)抑制剂 免疫相关甲状腺功能障碍(irTD) 甲状腺抗体 影响因素 总生存期(OS) 

分 类 号：R730.51[医药卫生—肿瘤]