To Investigate The Prognostic Factors And The Significance Of TKI In Advanced NSCLC With Wild-type EGFR

Objective: To investigate the prognostic factors and the related problems of TKI therapy about NSCLC patients with wild-type EGFR.Methods: We performed a review of 90 patients who presented with advanced NSCLC with wild-type EGFR in the 4th Hospital,Hebei Medical University from January 2015 to December 2016.Analyse the prognostic factors for survival;observe the DCR,ORR,PFS,OS,side effects' differences between two groups,which were divided into chemotherapy and TKIs groups according to the second-line treatment after failure in platinum-based double chemotherapy,and which were divided into first-line TKIs and second-line TKIs groups according to the time patients used TKIs.Results:1 90 patients were enrolled in the analysis of prognosis,including the factors about age,gender,performances status,smoking index,pathological type,stage,chronic disease,blood coagulation,metastasis,surgery,local treatment,vascular targeting treatment and the serum CEA,SCC,NSE,CY-211 level.The results showed that performances status,stage,surgery,blood coagulation,metastasis and the serum NSE,CY-211 level were correlated with the prognosis(P<0.05).By further multivariate Cox Regression analysis,it demonstrated the lower PS score,more organs with metastasis,and the serum CY-211 beyond the upper limit of normal were independent prognostic factors in NSCLC patients with wild-type EGFR,The risk of death increased respectively 2.589 times,1.986 times,and 3.546(1/0.282)times(P=0.041,P =0.006,P =0.007).2 The comparison between TKI and chemotherapy in second-lineAccording to the second-line treatment,30 patients experienced the failure of platinum based chemotherapy were divided into chemotherapy group(20)and TKI group(10).The patients in TKI group were elderly and had a bad performance status.The two groups had no significant differences in ORR,OS,side effects(P>0.05);the median PFS of chemotherapy group extended 2.6 months compared with TKI group(P =0.004);DCR was also better than TKI group(P=0.019).3 The comparison between the first-line TKI and the second-line TKIThe first-line TKI group had 14 patients.In this group the median OS was 6 months and the median PFS was 2 months.The second-line TKI group including 10 patients,the median OS was 31 months and the median PFS was 3 months(P =0.008,P =0.009).The ORR?DCR and adverse reaction between two groups had no significant differences(P >0.05).The patients were given TKI treatment mainly because of advanced age,poor PS and their own subjective factors.4 Selection of EGFR gene detection methodsIn 90 patients,34 cases(37.8%)were tested by blood ctDNA;45 cases(50%)by tissue;2 cases(2.2%)by pleural ctDNA;8 cases(8.9%)by tissue and blood;1 cases(1.1%)by pleural and blood ctDNA.90% patients only had once gene detection,and 8.9% patients had been tested for twice,and the other 1.1% patients had been tested for the third time.There were 8 patients were detected multiple genes,and more than 82 cases were detected only for EGFR gene mutations.5 Mutation of EGFR gene and other genesThere were 40 patients detected with ALK gene,and fusion mutation was found in 2 patients.Among the two patients with the detection of ten genes relating to non-small lung cancer,EGFR gene and other genes were all wild type.There were also six patients detecting multiple genes,and the results showed that based on the wild EGFR gene,one of the patients had EML4-ALK fusion mutation,one had the EGFR A767_V769dup and PI3 KCA mutation,one companied with HER-2 mutation,one had the RET,HDAC4,FLT4,NOTGH1,BTK mutations,and one was not associated with other genes variation.In the overall patients with wild-type EGFR gene,44.4% of the patients had further genetic testing,and 10% of the patients had the opportunities of targeted therapy.Conclusions:1 Low PS score,distant metastasis,and serum CY-211 beyond the upper limit of normal were independent adverse prognostic factors in advanced NSCLC patients with wild-type EGFR.2 Compared to the TKI group,the chemotherapy group had the advantages of PFS and DCR in the wild type EGFR patients after,but there was no significant difference in overall survival.3 The patients with poor performance and eldery age were more likely to choose TKI treatment earlier.