Significance Of Circulating Tumors Cells Combined With Pro-GRP And NSE Levels In Evaluating The Efficacy Of Chemotherapy For Patients With Small Cell Lung Cancer

Objective:1.To confirm that CTC,pro-GRP and NSE were correlated with the efficacy of SCLC chemotherapy.2.To establish CTC,pro-GRP,NSE criteria to evaluate the efficacy of SCLC chemotherapy,and compared with the RECIST standard to evaluate its reliability.Methods:40 patients with small cell lung cancer were selected from October 1,2015 to November 30,2016 in our department.The age,sex,smoking history,tumor size,tumor stage of the patients were summarized.The peripheral blood CTC,pro-GRP and NSE were detected before the first and the third cycle of chemotherapy.The CTC was detected by MACS enrichment and FISH,pro-GRP was detected by CMIA,NSE was detected by ECLIA,then the expression of CTC,pro-GRP and NSE were detected before the first and the third cycle of chemotherapy.Meanwhile,all patients underwent the Chest CT before the first and the third cycle of chemotherapy,to evaluate chemotherapy efficacy in patients with RECIST criteria.The number of CTC,pro-GRP and NSE after two cycles of chemotherapy reduced the number of CTC,pro-GRP and NSE before chemotherapy,and the values of CTC,pro-GRP and NSE(ΔCTC,Δpro-GRP,ΔNSE)were obtained.The difference ofΔCTC,Δpro-GRP and ΔNSE between PD group and CR+PR+SD group was compared with RECIST standard,then the relationship between CTC,pro-GRP,NSE and the curative effect of SCLC chemotherapy was obtained.Calculating ΔCTC’,Δpro-GRP’,ΔNSE’s four quantile,mean and Youden index,the maximum Youden index of four percentile or mean were as the standard parameters.Then we can establish the CTC,pro-GRP and NSE criteria to evaluate the efficacy of SCLC chemotherapy.We also compared the differences between CTC,pro-GRP,NSE and RECIST standard in judging the efficacy of chemotherapy.The sensitivity of the three criterion was compared.And the clinical data of patients were collected to analyze the relationship between the expression of CTC and clinical features.Results:In 40 SCLC patients,there were 35 males and 5 females,20 cases of age < 60 years and 20 cases of age more than 60 years,34 cases of smoking history and 6 cases no history of smoking,4 cases with newly diagnosed tumor size of T1,20 cases with newly diagnosed tumor size of T2,6 cases with newly diagnosed tumor size of T3,10 cases with newly diagnosed tumor size of T4,9 cases in the stage of III A,10 cases in the stage of III B,17 cases in the stage of IV with oligo-metastasis,4 cases in the stage of IV with multiplemetastases.In 40 patients with small cell lung cancer,the number CTC which was detected before and after chemotherapy was 33、35,the positive rate was 82.5%、87.5%,respectively.The expression of pro-GRP higher than normal level which was detected before and after chemotherapy was 29、20,the positive rate was 72.5%、50%,respectively.The expression of NSE higher than normal level which was detected before and after chemotherapy was 28、11,the positive rate was 70%、27.5%,respectively.According to RECIST standard,the mean ofΔCTC in PD group and CR+PR+SD group were 0.8、-1.66,respectively.And there was significant difference between the two groups(P=0.021).The same phenomenon were observed inΔpro-GRP(P=0.013)andΔNSE(P=0.038).There was a negative correlation between CTC or pro-GRP or NSE and the curative effect of chemotherapy,that is,the better the curative effect of chemotherapy,the lower the expression of CTC,pro-GRP and NSE.The value with the maximum Youden index ofΔCTC,Δpro-GRP,ΔNSE were-1,-394.00 pg/ml,-16.00ug/L,respectively.Then we useΔCTC reducing greater than or equal to 1 as tumor controlled,reducing less than 1 as tumor progressing,Δpro-GRP reducing greater than or equal to 394 pg/ml as tumor controlled,reducing less than 394 pg/ml as tumor progressing,ΔNSE reducing greater than or equal to 16ug/L as tumor controlled,reducing less than 16ug/L as tumor progressing.There is a consistency in evaluating the efficacy of chemotherapy between CTC or pro-GRP or NSE evaluation criteria and RECIST criteria(P>0.05).CTC,pro-GRP and NSE standards evaluating the efficacy of chemotherapy is as the same as RECIST efficacy evaluation(P>0.05).And the three joint detection can improve the sensitivity of efficacy judgment.According to CTC evaluation criteria,no significant correlation was found in age,sex,smoking,tumor size,tumor stage,tumor control between PD group and CR+PR+SDgroup(P<0.05).Conclusion:There was a negative correlation between the change of CTC,pro-GRP,NSE and the efficacy of chemotherapy.CTC,pro-GRP,NSE three kinds of parameters evaluating the efficacy of SCLC chemotherapy is consistent with the RECIST standard.Combing detection of CTC,pro-GRP and NSE to evaluate the efficacy of chemotherapy in patients with SCLC has a higher sensitivity.