关键词: 甲状腺功能异常, 程序性死亡受体-1, 晚期肿瘤, 生存, 治疗结果

Abstract:

Objective To investigate the relationship between thyroid function abnormality-immune related adverse event （TFA-irAE） and treatment efficacy and survival in advanced cancer patients treated with programmed death-1 （PD-1） inhibitors. Methods The clinical data of 90 patients with advanced cancer who received 6 cycles of PD-1 inhibitor treatment from January 2021 to June 2022 in Department of Oncology of Yuncheng Central Hospital Affiliated to Shanxi Medical University were collected. Serum levels of thyroid stimulating hormone （TSH），free thyroxine （FT₄），thyroid peroxidase antibody （TPOAb），and thyroglobulin antibody （TGAb） were measured by chemiluminescence immunoassay in patients after PD-1 inhibitor treatment，and the incidence of TFA-irAE was observed in the patients after 6 cycles of therapy. According to the occurrence of TFA-irAE，the patients were divided into TFA-irAE occurrence group （n=40） and TFA-irAE non-occurrence group （n=50），the therapeutic efficacy and survival of the two groups were calculated and compared. The thyroid function indexes of patients with different efficacy （33 cases in effective group and 57 cases in ineffective group） and patients with different prognosis （30 cases in survival group, 60 cases in death group） were compared，and the influencing factors of efficacy and survival were analyzed by multivariate logistic regression and Cox analysis. Kaplan-Meier survival curve was drawn，and the survival of TFA-irAE occurrence group and TFA-irAE non-occurrence group were compared by log-rank test. Results One year after treatment，the treatment effective rate of TFA-irAE occurrence group and TFA-irAE non-occurrence group were 42.5% （17/40），32.0% （16/50），respectively，with no statistically significant difference （χ²=1.06，P=0.304）. After 6 cycles of PD-1 inhibitor treatment，serum levels of TSH [（2.56±0.41） mU/ml vs. （3.11±0.53） mU/ml]，TPOAb [（56.78±5.72） U/ml vs. （62.67±6.31） U/ml] and TGAb [（81.57±8.23） U/ml vs. （92.34±9.31） U/ml] in the effective group were significantly lower than those in the ineffective group，with statistically significant differences （t=4.45，P<0.001； t=3.89，P<0.001； t=5.29，P<0.001）. The serum levels of TSH [（2.69±0.46） mU/ml vs. （3.06±0.65） mU/ml]，FT₄ [（10.45±1.13） pmol/L vs. （11.50±1.36） pmol/L]，TPOAb [（56.27±5.61） U/ml vs. （62.47±6.34） U/ml] and TGAb [（81.62±8.31） U/ml vs. （91.73±9.35） U/ml] in the survival group were significantly lower than those in the death group，with statistically significant differences （t=2.27，P=0.025； t=3.02，P=0.003； t=3.79，P<0.001； t=4.19，P<0.001）. Multivariate logistic regression analysis showed that TSH （OR=1.52，95%CI：1.13-2.05，P=0.006），TPOAb （OR=1.42，95%CI：1.13-1.78，P=0.002） and TGAb （OR=1.35，95%CI：1.05-1.73，P=0.018） were all independent factors affecting the efficacy of patients with advanced cancer treated with PD-1 inhibitors. Multivariate Cox regression analysis showed that TSH （HR=1.42，95%CI：1.06-1.92，P=0.030），TPOAb （HR=1.31，95%CI：1.05-1.64，P=0.018），TGAb （HR=1.41，95%CI：1.09-1.83，P=0.008） and FT₄ （HR=1.36，95%CI：1.02-1.81，P=0.038） were all independent factors affecting the survival of patients with advanced cancer treated with PD-1 inhibitors. Survival analysis showed that the median overall survival in the TFA-irAE occurrence group and the TFA-irAE non-occurrence group were 10.8 and 8.0 months，respectively，with a statistically significant difference （χ²=9.53，P=0.002）. Conclusion Although the occurrence of TFA-irAE may have less effect on the efficacy of advanced tumor patients treated with PD-1 inhibitors，it may affect the survival of patients. TSH，TPOAb and TGAb are all independent influencing factors for the efficacy of patients with advanced tumors treated with PD-1 inhibitors，while TSH，TPOAb，TGAb and FT₄ are independent influencing factors for the survival of patients with advanced tumors treated with PD-1 inhibitors.

Key words: Thyroid function abnormality, Programmed death-1, Advanced cancer, Survival, Treatment outcome