Influencing factors of immune-related thyroid dysfunction and overall survival in cancer patients treated with PD-1/PD-L1 inhibitors
- VernacularTitle: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
- Author:
Fengping LEI
1
;
Juanchuan YAO
2
;
Ting MA
1
;
Haichen LI
1
;
Wei CUI
1
Author Information
- Publication Type:Journal Article
- Keywords: programmed death-1(PD-1)/programmed death ligand-1(PD-L1) inhibitor; immune-related thyroid dysfunction (irTD); thyroid antibody; influencing factor; overall survival (OS)
- From: Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(6):967-974
- CountryChina
- Language:Chinese
- Abstract: [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 significantly longer OS (HR=0.228, 95% CI: 0.079-0.656, P=0.006). [Conclusion] The severity of irTD was predominantly grades 1-2, with grades 3-4 being rare. Positive baseline thyroid antibodies were an independent risk factor for the development of irTD. Patients who develop irTD have a longer OS, which may be due to their stronger immune response.
