Correlative Study On Blood Inflammatory Composite Indexes And Prognosis In Non-small Cell Lung Cancer Patients With Immunotherapy

Objective:At present,more and more patients with non-small cell lung cancer(NSCLC)have good survival outcomes due to immunotherapy.However,some patients do not benefit from it.Programmed cell death protein-ligand 1(PD-L1)is currently one of the most widely used biomarkers for immunotherapy,but more convenient biomarkers still need to predict the prognosis of immunotherapy in clinical practice.Inflammation,one of the important characteristics of tumors,can promote tumor cell proliferation,immune escape,tumor angiogenesis,epithelial-mesenchymal transition and apoptosis,which is closely related to the poor prognosis of lung cancer patients.However,little is known about the relationship between blood inflammatory composite indexes and prognosis in NSCLC patients undergoing immunotherapy.In this study,we will explore the prognostic factors of NSCLC patients receiving immunotherapy based on their basic clinical characteristics and blood inflammatory composite indexes before treatment,with a view to providing convenient and high quality biomarkers for clinical application of immunotherapy.Methods:This study was a retrospective study of 102 NSCLC patients who received treatment with immune checkpoint inhibitors in the Department of Thoracic Oncology,Shanxi Bethune Hospital from January 2019 to December 2021.The basic clinical characteristics such as gender,age,pathological type,clinical stage,performance status(PS)score,smoking history,body mass index(BMI),chronic respiratory disease history,PD-L1 expression,and treatment were collected.The peripheral blood data before immunotherapy were recorded.The optimal cutoff values of neutrophil to lymphocyte ratio(NLR),platelet to lymphocyte ratio(PLR),monocyte to lymphocyte ratio(MLR),systemic immune-inflammation index(SII),prognostic nutrition index(PNI),C-reactive protein to albumin ratio(CAR),albumin to alkaline phosphatase ratio(AAPR),albumin to fibrinogen ratio(AFR),and inflammatory burden index(IBI)were calculated by receiver operating characteristic(ROC)curve and then the nine inflammatory composite indexes were grouped according to the values.The Kaplan-Meier analysis was used to compare the survival curves between groups,and Log-rank test were used for the univariate analysis of clinical characteristics and blood inflammatory composite indexes to assess the impact on progression-free survival(PFS)of NSCLC patients.The factors that were significant in the univariate analysis were selected into the COX proportional hazards model analysis to screen out indicators that have independent predictive effects on the prognosis of NSCLC patients with immunotherapy.Chi-square test and Logistic regression analysis were used to analyze the correlation between blood inflammatory composite indexes and the basic clinical characteristics and immune-related adverse reactions(ir AE).P<0.05 indicated that the difference was statistically significant.Results:1.102 NSCLC patients were included in this study.43 patients(42.2%)experienced ir AE.The median PFS was 440 days.2.ROC curves and Youden indexes showed that the optimal cutoff value of NLR in this study was 2.78(AUC=0.617,95%CI=0.503-0.732,P=0.049),and that of MLR was0.44(AUC=0.598,95%CI=0.484-0.711,P=0.103),that of PLR was 139.14(AUC=0.565,95%CI=0.442-0.688,P=0.279),that of SII was 572.03(AUC=0.600,95%CI=0.488-0.712,P=0.094),that of PNI was 42.63(AUC=0.564,95%CI=0.445-0.683,P=0.284),that of CAR was 0.12(AUC=0.538,95%CI=0.422-0.654,P=0.529),and that of AAPR was 0.42(AUC=0.535,95%CI=0.419-0.651,P=0.556).The optimal cutoff value was 10.93 for AFR(AUC=0.555,95%CI=0.435-0.674,P=0.360)and 17.69 for IBI(AUC=0.575,95%CI=0.462-0.689,P=0.206).3.Kaplan-Meier and Log-rank univariate analyses showed that the PFS of patients in the low NLR group was longer than that of patients in the high NLR group(P=0.015).PFS of patients in the low PLR group was longer than that of patients in the high PLR group(P=0.043).PFS of patients with low SII was longer than that of patients with high SII(P=0.027).PFS of patients with high AAPR was longer than that of patients with low AAPR(P=0.002).PFS of patients with high AFR group was longer than that of patients with low AFR group(P=0.036).PFS was longer in patients with low IBI than in patients with high IBI(P=0.036).There were no significant differences in PFS between the groups based on gender,age,pathological type,clinical stage,PS score,smoking history,BMI,chronic respiratory disease history,PD-L1 expression,treatment models,MLR,PNI,and CAR(P>0.05).4.Cox multivariate analysis showed that AAPR(HR=0.458,95% CI: 0.278–0.755,P=0.002)and NLR(HR=1.864,95%CI: 1.139–3.051,P=0.013)were closely related to PFS of patients and could be used as independent prognostic factors for NSCLC patients with immunotherapy.5.Chi-square test and Logistic regression analysis showed that gender,age,pathological type,clinical stage,PS score,smoking history,BMI,chronic respiratory disease history,PD-L1 expression,NLR,MLR,PLR,SII,PNI,CAR,AAPR,AFR,and IBI had no significant correlation with the occurrence of ir AE in the patients(P>0.05).Conclusion:1.In this study,patients with low NLR(<2.78),low PLR(<139.14),low SII(<572.03),high AAPR(≥0.42),high AFR(≥10.93)and low IBI(<17.69)had longer PFS.2.AAPR and NLR can be used as prognostic markers for NSCLC patients with immunotherapy.AAPR and NLR,as easily obtained indicators of inflammatory responses,with the advantages of low cost,simple method and rapid detection,may play an important role in predicting the prognosis.