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中华肺部疾病杂志(电子版)

中华肺部疾病杂志(电子版) ›› 2023, Vol. 16 ›› Issue (06) : 784 -788. doi: 10.3877/cma.j.issn.1674-6902.2023.06.008

论著

PD-1抑制剂对肺癌治疗致甲状腺相关病变的影响因素分析
任洁, 檀崇斌, 张振华†(), 刘晨露   
  1. 242300　宁国，宁国市人民医院药剂科
    242300　宁国，宁国市人民医院肿瘤内科
  • 收稿日期:2023-11-07 出版日期:2023-12-25
  • 通信作者: 张振华
  • 基金资助:
    安徽省自然科学基金项目(2108085MH311)

Analysis of influencing factors of thyroid related lesions induced by PD-1 inhibitors in the treatment of lung cancer

Jie Ren, Chongbin Tan, Zhenhua Zhang†(), Chenlu Liu   

  1. Department of Pharmacy, Ningguo People′s Hospital, Ningguo 2242300, China
    Department of Medical Oncology, Ningguo People′s Hospital, Ningguo 2242300, China
  • Received:2023-11-07 Published:2023-12-25
  • Corresponding author: Zhenhua Zhang
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任洁, 檀崇斌, 张振华, 刘晨露. PD-1抑制剂对肺癌治疗致甲状腺相关病变的影响因素分析[J]. 中华肺部疾病杂志(电子版), 2023, 16(06): 784-788.

Jie Ren, Chongbin Tan, Zhenhua Zhang, Chenlu Liu. Analysis of influencing factors of thyroid related lesions induced by PD-1 inhibitors in the treatment of lung cancer[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2023, 16(06): 784-788.

目的

分析程序性死亡受体1(programmed death receptor 1, PD-1)抑制剂对肺癌治疗致甲状腺相关病变的影响因素。

方法

选择2021年1月至2022年12月我院收治的57例肺癌患者为对象，接受PD-1抑制剂治疗，1个治疗周期为3周，治疗6个周期，发生甲状腺相关病变21例分为观察组，未发生甲状腺相关病变36例为对照组。对比临床资料，分析PD-1抑制剂在肺癌治疗中发生甲状腺相关病变的疗效。

结果

观察组治疗后发生亚临床甲减11例(52.38%)、甲减6例(28.57%)、甲亢3例(14.29%)、亚临床甲亢1例(4.76%)。观察组女性14例(66.67%)、身体质量指数(BMI)>25 kg/m2 12例(57.14%)、临床分期为Ⅳ期15例(71.43%)、甲状腺内部回声不均匀13例(61.90%)，对照组女性7例(19.44%)、身体质量指数(BMI)>25 kg/m2 12例(33.33%)、临床分期为Ⅳ期10例(27.78%)、甲状腺内部回声不均匀3例(8.33%)，P<0.05。观察组卡氏功能状态评分(KPS)评分(66.13±3.27)分低于对照组(75.44±4.41)分，P<0.05。二元Logistic回归分析显示，女性(OR＝2.735，95%CI：1.202～6.221)、病程≥1年(OR＝3.171，95%CI：1.394～7.213)、BMI>25 kg/m2(OR＝3.557，95%CI：1.564～8.092)、甲状腺内部回声不均匀(OR＝3.827，95%CI：1.682～8.705)为PD-1抑制剂在肺癌治疗中发生甲状腺相关病变的影响因素(P<0.05)。

结论

PD-1抑制剂对肺癌治疗致甲状腺相关病变风险高，女性、病程较长、超重、甲状腺内部回声不均匀为甲状腺相关病变风险因素。

关键词: 程序性死亡受体1抑制剂, 支气管肺癌, 甲状腺相关病变, 影响因素
Objective

To analyze the influencing factors of thyroid related lesions caused by programmed death receptor 1 (PD-1) inhibitors in the treatment of lung cancer.

Methods

The clinical data of 57 patients with lung cancer admitted to the oncology Department of the hospital from January 2021 to December 2022 were retrospectively analyzed. All patients received PD-1 inhibitor treatment, a treatment cycle was 3 weeks, and within 6 treatment cycles, Twenty-one cases with thyroid related lesions were divided into observation group and 36 cases without thyroid related lesions were divided into control group. The clinical data of observation group and control group were compared. The influencing factors of thyroid related lesions induced by PD-1 inhibitors in the treatment of lung cancer were analyzed.

Results

In the observation group, subclinical hypothyroidism in 11 cases (52.38%), hypothyroidism in 6 cases (28.57%), hyperthyroidism occurred in 3 cases (14.29%) and subclinical hyperthyroidism in 1 case (4.76%). In the observation group, there were 14 females (66.67%), 12 females (57.14%) with body mass index (BMI)>25 kg/m2, 15 females (71.43%) with clinical stage Ⅳ, and 13 females (61.90%) with uneven thyroid internal echo. In the control group, there were 7 females (19.44%), 12 females (33.33%) with body mass index (BMI)>25 kg/m2, 10 females (27.78%) with stage Ⅳ, and 3 females (8.33%) with uneven thyroid internal echo (P<0.05). The KPS score of the observation group (66.13±3.27) was lower than that of the control group (75.44±4.41), (P<0.05). Binary Logistic regression analysis showed that women (OR=2.735, 95%CI: 1.202-6.221), disease duration ≥1 year (OR=3.171, 95%CI: 1.394-7.213), BMI>25 kg/m2 (OR=3.557, 95%CI: 1.564-8.092) and uneven internal thyroid echo (OR=3.827, 95%CI: 1.682-8.705) were the influential factors for thyroid related lesions caused by PD-1 inhibitors in the treatment of lung cancer (P<0.05).

Conclusion

The risk of thyroid related lesions caused by PD-1 inhibitors in lung cancer treatment is higher, and the risk of thyroid related lesions is higher in women, lung cancer patients with long disease course, overweight, and uneven internal thyroid echo.

Key words: Programmed death receptor 1 inhibitor, Bronchogenic carcinoma, Thyroid related lesions, Influencing factor
表1 两组患者临床资料比较[n(%)]
临床资料 观察组(n＝21) 对照组(n＝36) t/χ2值 P值
PD-1抑制剂类型        
注射用卡瑞利珠单抗 1(4.76) 6(16.67) 1.825 0.533
替雷利珠单抗注射液 16(76.19) 23(63.89)    
信迪利单抗注射液 4(19.05) 7(19.44)    
吸烟史 16(76.19) 30(83.33) 0.435 0.510
饮酒史 14(70.83) 22(61.11) 0.598 0.439
基础疾病        
糖尿病 12(57.14) 26(72.22) 1.357 0.244
高血压 10(47.62) 20(55.56) 0.335 0.563
冠心病 5(23.81) 13(36.11) 0.929 0.335
TSH基线水平(μIU/ml) 2.24±0.37 2.30±0.35 0.611 0.543
脑转移 8(38.10) 15(41.67) 0.070 0.791
淋巴结转移 12(57.14) 23(63.89) 0.255 0.614
骨转移 5(23.81) 9(25.00) 0.010 0.920
肺内或胸膜转移 3(14.29) 6(16.67) 0.057 1.000
癌症家族史 10(47.62) 17(47.22) 0.001 0.977
病理类型        
肺鳞癌 4(19.05) 8(22.22) 0.080 0.777
肺腺癌 17(80.95) 28(77.78)    
放疗史 17(80.95) 31(86.11) 0.265 0.606
化疗史 17(80.95) 29(80.56) 0.001 0.971
表2 PD-1抑制剂肺癌治疗中发生甲状腺相关病变的因素结果
自变量 β SE Wald P值 OR 95%CI
女性 1.006 0.437 5.299 0.000 2.735 1.202～6.221
病程≥1年 1.154 0.362 10.162 0.000 3.171 1.394～7.213
BMI>25 kg/m2 1.269 0.357 12.635 0.000 3.557 1.564～8.092
甲状腺内部回声不均匀 1.342 0.408 10.819 0.000 3.827 1.682～8.705
1
吴国明，钱桂生. 非小细胞肺癌靶向治疗研究进展及新理念[J/CD]. 中华肺部疾病杂志(电子版), 2019, 12(4): 405-408.
2
秦　娜，马红霞，靳光付，等. 肺癌流行病学研究年度进展2022[J]. 中华医学杂志，2023, 103(14): 1068-1073.
3
Harethardottir H, Jonsson S, Gunnarsson O, et al. Advances in lung cancer diagnosis and treatment-a review[J]. Laeknabladid, 2022, 108(1): 17-29.
4
何文举，杨美菊，刘占祥，等. 血清外泌体来源的microRNA-4429水平高提示非小细胞肺癌根治性放化疗预后良好[J]. 中华检验医学杂志，2021, 44(6): 480-485.
5
Santomasso BD, Nastoupil LJ, Adkins S, et al. Management of immune-related adverse events in patients treated with chimeric antigen receptor T-Cell therapy: ASCO guideline[J]. J Clin Oncol, 2021, 39(35): 3978-3992.
6
吴建辉，储香玲，王李强，等. 中国肺癌患者真实世界免疫检查点抑制剂相关性肺炎的流行病学分析[J]. 中国癌症杂志，2022, 32(6): 469-477.
7
Wright JJ, Powers AC, Johnson DB. Endocrine toxicities of immune checkpoint inhibitors[J]. Nat Rev Endocrinol, 2021, 17(7): 389-399.
8
解　荣，罗瑞君，李　颖，等. 恶性肿瘤病人免疫治疗并发中重度免疫相关不良反应体验的质性研究[J]. 护理研究，2023, 37(11): 2055-2060.
9
Weetman AP. An update on the pathogenesis of hashimoto′s thyroiditis[J]. J Endocrinol Invest, 2021, 44(5): 883-890.
10
刘雅娟，莫丽钦，张晓诺，等. 免疫检查点抑制药相关甲状腺功能障碍的预测及疗效预后临床研究[J]. 中国临床药理学杂志，2022, 38(22): 2668-2673.
11
Paschou SA, Stefanaki K, Psaltopoulou T, et al. How we treat endocrine complications of immune checkpoint inhibitors[J]. ESMO Open, 2021, 6(1): 100011.
12
Byrne MM, Lucas M, Pai L, et al. Immune-related adverse events in cancer patients being treated with immune checkpoint inhibitors[J]. Eur J Haematol, 2021, 107(6): 650-657.
13
中华医学会肿瘤学分会，中华医学会杂志社. 中华医学会肺癌临床诊疗指南(2023版)[J]. 中华医学杂志，2023, 103(27): 2037-2074.
14
Yang W, Chang L, Guo Q, et al. Programmed cell death protein-1 inhibitors in the treatment of digestive system tumors in Chinese population: an observational study of effectiveness and safety[J]. Ann Palliat Med, 2021, 10(8): 9015-9024.
15
Iwama S, Kobayashi T, Yasuda Y, et al. Immune checkpoint inhibitor-related thyroid dysfunction[J]. Best Pract Res Clin Endocrinol Metab, 2022, 36(3): 101660.
16
王　群，蒋晶晶，陆志强，等. 程序性死亡受体-1抑制剂相关内分泌腺体疾患26例临床特征分析[J]. 江苏大学学报(医学版), 2023, 33(2): 156-161.
17
霍庚崴，宋　莹，贾沙沙，等. PD-1/PD-L1抑制剂联合化疗对比化疗一线治疗晚期非小细胞肺癌疗效及安全性的Meta分析[J]. 中国肿瘤生物治疗杂志，2020, 27(3): 309-314.
18
Luo J, Martucci VL, Quandt Z, et al. Immunotherapy-mediated thyroid dysfunction: genetic risk and impact on outcomes with PD-1 blockade in non-small cell lung cancer[J]. Clin Cancer Res, 2021, 27(18): 5131-5140.
19
顾阳春，刘　颖，谢　超，等. 程序性死亡蛋白-1抑制剂治疗晚期肺癌出现垂体免疫不良反应3例[J]. 北京大学学报(医学版), 2022, 54(2): 369-375.
20
Wu Y, Wang Z, Bai H, et al. Thyroid dysfunction during PD-1 inhibitor treatment in patients with cancer: incidence and association with progression-free survival[J]. Oncol Lett, 2022, 24(3): 309.
21
Poppe K. Management of endocrine disease: Thyroid and female infertility: more questions than answers？[J]. Eur J Endocrinol, 2021, 184(4): 123-135.
22
Cheung YM, Wang W, McGregor B, et al. Associations between immune-related thyroid dysfunction and efficacy of immune checkpoint inhibitors: a systematic review and meta-analysis[J]. Cancer Immunol Immunother, 2022, 71(8): 1795-1812.
23
Muir CA, Clifton-Bligh RJ, Long GV, et al. Thyroid immune-related adverse events following immune checkpoint inhibitor treatment[J]. J Clin Endocrinol Metab, 2021, 106(9): 3704-3713.
24
侯静文. PD-1抑制剂相关甲状腺不良反应的影响因素分析[D]. 河南：郑州大学，2021.
25
张　勤. 免疫检查点抑制剂相关性甲状腺功能障碍的临床特征及影响因素分析[D]. 南昌大学医学部，2022.
26
张文洁，宋佳怡，窦　真，等. 炎症因子对卵泡发育的影响[J]. 中华生殖与避孕杂志，2021, 41(4): 377-381.
27
Iwama S, Kobayashi T, Yasuda Y, et al. Increased risk of thyroid dysfunction by PD-1 and CTLA-4 blockade in patients without thyroid autoantibodies at baseline[J]. J Clin Endocrinol Metab, 2022, 107(4): 1620-1630.
28
Zhou X, Iwama S, Kobayashi T, et al. Risk of Thyroid dysfunction in PD-1 blockade is stratified by the pattern of TgAb and TPOAb positivity at baseline[J]. J Clin Endocrinol Metab, 2023, 108(10): e1056-e1062.
29
Wu H, Xiong F, Bao X, et al. Immune checkpoint blockade PD-1 therapy for primary liver cancer: incidence and influencing factors of thyroid dysfunction[J]. Infect Agent Cancer, 2022, 17(1): 64.
30
D′Andrea G, Lassalle S, Guevara N, et al. From biomarkers to therapeutic targets: the promise of PD-L1 in thyroid autoimmunity and cancer[J]. Theranostics, 2021, 11(3): 1310-1325.
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