Relationship between TFA-irAE after anti-PD-1 therapy and survival in advanced cancer patients
	    		
		   		
		   			
		   		
	    	
    	 
    	10.3760/cma.j.cn371439-20240215-00080
   		
        
        	
        		- VernacularTitle:晚期肿瘤患者PD-1单抗治疗后免疫相关甲状腺功能异常与生存情况的相关性
 
        	
        	
        	
        		- Author:
	        		
		        		
		        		
			        		Wei GUO
			        		
			        		
			        		
			        			1
			        			
			        		
			        		
			        		
			        		
			        		;
		        		
		        		
		        		
			        		Donghui WANG
			        		
			        		;
		        		
		        		
		        		
			        		Zhenhua WANG
			        		
			        		;
		        		
		        		
		        		
			        		Zhaojun XUE
			        		
			        		
		        		
		        		
		        		
		        		
		        			
			        		
			        		Author Information
			        		
		        		
		        		
			        		
			        		
			        			1. 山西医科大学附属运城市中心医院肿瘤科,运城 044000
			        		
		        		
	        		
        		 
        	
        	
        	
        	
        		- Keywords:
        			
	        			
	        				
	        				
			        		
				        		Thyroid function abnormality;
			        		
			        		
			        		
				        		Programmed death-1;
			        		
			        		
			        		
				        		Advanced cancer;
			        		
			        		
			        		
				        		Survival;
			        		
			        		
			        		
				        		Treatment outcome
			        		
			        		
	        			
        			
        		
 
        	
            
            
            	- From:
	            		
	            			Journal of International Oncology
	            		
	            		 2024;51(8):481-486
	            	
            	
 
            
            
            	- CountryChina
 
            
            
            	- Language:Chinese
 
            
            
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		        	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 (FT 4), 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], FT 4 [ (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 FT 4 ( 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 FT 4 are independent influencing factors for the survival of patients with advanced tumors treated with PD-1 inhibitors.