The Prognostic Value Of Immune Environmental Factors IEF1 And IEF2 In EGFR Positive Stage Ⅲ And Ⅳ NSCLC Treated With TKIs

Background and Objective:The incidence rate of lung cancer is increasing year by year,which affects the quality of life of human beings.It accounts for the first place of all cancer mortality,of which NSCLC accounts for about 80%.The positive mutation rate of epidermal growth factor receptor（EGFR）in Asians is about 50%,which is the natural dominant population using EGFR TKIs.Compared with the traditional chemotherapy regimen,EGFR TKIs can target and kill NSCLC cells with positive driving gene.It has the advantages of prolonging the survival time and improving the quality of life of tumor patients,less hematological toxicity and gastrointestinal reactions,tolerable adverse reactions,oral administration and easier passage through blood-brain barrier.However,the clinical benefit rate is only about 80%,and a few patients can not respond effectively to treatment.Therefore,it is necessary to study the clinical and pathological characteristics of patients with EGFR TKIs,which may affect the clinical efficacy of patients with EGFR TKIs.This study proposes new joint indicators IEF1 and IEF2 to make up for this deficiency.IEF1=neutrophils*monocytes*fibrinogen/lymphocytes/albumin,IEF2=neutrophils*platelets*fibrinogen/lymphocytes,which can reflect the state of inflammation,immune regulation and nutritional metabolism to a certain extent.At the same time,for advanced NSCLC with positive EGFR mutation,it reflects the status of human nutritional metabolism,inflammation and immune regulation.The relationship between IEF1 and IEF2 and the prognosis of patients with EGFR mutation positive NSCLC,and the comparison between IEF1 and IEF2 and the classic neutrophil/lymphocyte ratio NLR and systemic immune inflammation index SII have never been studied.The purpose of this study was to explore the prognostic value of IEF1 and IEF2 levels before treatment in patients with EGFR mutation positive stage III-IV NSCLC.Methods:The clinical data of 73 patients with EGFR mutation positive advanced non-small cell lung cancer treated with erlotinib,gefitinib or ektinib in Qingdao Municipal Hospital Affiliated to Qingdao University from June 1,2015 to May 1,2019were collected.Before taking TKIs,patients completed routine blood coagulation test 1-2 weeks.Using formula:IEF1=mon*（10⁹/L）×Neu*（10⁹/L）×Fibro*（10⁹/L）/Lym*（10⁹/L）/ALB（g/L）,IEF2=plat*（10⁹/L）×Neu*（10⁹/L）×Fibro*（10⁹/L）/lym*10⁹/L),in which mon*,plat*,neu*,fibro*,lym*and ALB represent the number of monocytes,platelets,neutrophils,fibrinogen,lymphocytes and serum albumin respectively,so as to obtain IEF1 and IEF2 values.The optimal critical values of IEF1 and IEF2 will be determined by ROC（receiver operating characteristic）curve,All patients were divided into high IEF1 group,high IEF2 group,low IEF1 group and low IEF2 group.At the same time,Cox proportional hazards model was used to analyze the prognostic factors of patients.Through Kaplan Meier analysis,m PFS（median progression free survival）of patients in high IEF1 group,high IEF2 group,low IEF1group and low IEF2 group were obtained.Log rank test was used to compare the differences between groups.We also compared these data with the confirmatory data of neutrophil/lymphocyte NLR and systemic immune inflammatory factor SII,which are closely related to the prognosis of non-small cell lung cancer.Results:According to ROC analysis results,IEF 1=1.066×10¹⁷,IEF2=2.007×10 ¹²is the critical value.Kaplan Meier analysis:m PFS in low IEF1 group was 18.0months,while m PFS in high IEF1 group was 8.0 months（P<0.001）,m PFS in low IEF2 group was 20.0 months,and m PFS in high IEF2 group was 8.0 months（P<0.001）.Cox multivariate regression analysis showed that IEF1 value,IEF2 value,SII value,NLR value,age,tumor stage,neutrophil count,monocyte count and lymphocyte count were independent influencing factors of m PFS in patients with EGFR mutant advanced NSCLC treated with EGFR TKIs,all P<0.05.At the same time,Cox univariate analysis showed that serum albumin,lymphocyte count,IEF1 value,IEF2 value,SII value and NLR value had significant effects on m PFS,P<0.01.Conclusions:1.This real-world study showed that IEF1 and IEF2 levels before treatment were independent influencing factors of m PFS in patients with EGFR positive stage III and IV NSCLC treated with EGFR targeted tyrosine kinase inhibitors（P<0.05）.Patients with high IEF1 and IEF2 tended to have shorter PFS.2.IEF1 and IEF2 levels before treatment are expected to be prognostic indicators for EGFR tyrosine kinase inhibitors in patients with EGFR mutation positive stage III-IV NSCLC.The indicators of this study need to be verified by more clinical trials.