| Objective:The correlation between the concentration and change of circulating tumor DNA(ctDNA)and the chemotherapy efficacy of advanced non-small cell lung cancer(NSCLC)was analyzed,and the value of ctDNA quantitative analysis to evaluate the chemotherapy efficacy of advanced NSCLC was discussed.Methods: From October 2017 to July 2019,22 patients with primary non-small cell lung cancer diagnosed as stage IIIB-IV by histopathology or imaging were collected from the tumor area of the Affiliated Hospital of the University of South China according to the inclusion,exclusion and exclusion criteria,and were followed up until December 31,2019.General clinical data(sex,age,smoking history,pathological classification,clinical stage)were collected.All patients were treated with a dual drug regimen containing platinum.Five milliliter elbow vein blood were collected in the first week before chemotherapy,two cycles after chemotherapy and four cycles after chemotherapy,respectively.Plasma samples were separated and ctDNA was extracted by magnetic bead method for quantitative analysis.For the patients prechemotherapy in the group,the maximum cross-sectional area of lung tumor at that time was recorded as the baseline value of lung tumor before chemotherapy.After one month of chemotherapy,CT scan was performed again to obtain the maximum cross-sectional area of the tumor.The tumor regression rate R([baseline value of lung tumor prechemotherapy-maximum cross-sectional area of lung tumor postchemotherapy / baseline value of lung tumor pre-chemotherapy)was calculated to evaluate the short-term chemotherapy efficacy.The longterm efficacy of chemotherapy was evaluated by progression-free survival(PFS).To evaluate the value of ctDNA quantitative analysis in evaluating the chemotherapy efficacy of NSCLC,the correlation between ctDNA concentration and its change and regression rate,the difference between PFS in different clinical characteristics,tumor regression rate and ctDNA concentration drop after four cycles of chemotherapy were analyzed.SPSS 22.0 software was used to measure the ctDNA concentration before and after chemotherapy by ANOVA of single factor repeated measurement;Pearson correlation analysis was used for analyzing the ctDNA concentration and difference before and after chemotherapy and the tumor regression rate R;and Spearman correlation analysis was used to analyze the regression rate and general clinical characteristics.We defined R<50% as the stable group(SD group)and R ≥ 50% as the remission group(PR group)according to WHO criteria for objective evaluation of tumor efficacy.At the same time,it was defined that the decrease of ctDNA concentration after 4 cycles of chemotherapy compared with the baseline value before chemotherapy was 2 ng / μ L,D ≥ 2 ng / μ l was the high response group,D < 2 ng / μ l was the low response group.T-test was used to analyze the difference of ctDNA concentration between SD group and PR group.T-test was performed on the PFS mean levels of the patients in different gender groups,age groups(65 years old as the boundary),smoking history groups,pathological type groups,groups of ctDNA decrease after 4 cycles of chemotherapy and regression rate groups.The difference was statistically significant(P < 0.05).Result:1.22 cases of NSCLC patients before chemotherapy,after 2 cycles of chemotherapy and after 4 cycles of chemotherapy overall comparison of single-factor repeated measurement analysis of variance test statistics F = 35.949,P = 0.00 Significant statistical significance.At the same time,the ctDNA concentrations measured at different time points were statistically described respectively: the average levels of ctDNA concentrations before chemotherapy,after 2 cycles of chemotherapy,and after 4 cycles of chemotherapy were 5.49 ± 1.17,7.19 ± 1.13,4.0 ± 4.95ng/ μ l,respectively.The concentration of ctDNA before chemotherapy to 2 cycles after chemotherapy showed an upward trend,and the concentration of ctDNA after 2 cycles to 4 cycles after chemotherapy showed a downward trend.2.The 22 NSCLC patients were grouped according to the tumor regression rate,including 7 cases in the PR group and 15 cases in the SD group,and the regression rate was between 0.02 and 0.77.T test was performed on the ctDNA concentration and change value of the PR and SD groups.The results showed that there was no statistically significant difference between the groups of ctDNA concentration levels before chemotherapy and after 2 cycles of chemotherapy(P = 0.832,0.347);there were significant statistical differences between the groups of ctDNA concentration after 4 cycles of chemotherapy(P = 0.001);the difference in ctDNA concentration after 2 cycles of chemotherapy and before chemotherapy(primary difference)was not statistically significant(P = 0.059);the difference in ctDNA concentration before chemotherapy,after 2 cycles of chemotherapy and after 4 cycles of chemotherapy(Second difference and third difference)The differences between the groups were statistically significant(P = 0.003,0.030).Among the PR groups,the mean of ctDNA concentration before chemotherapy,after 2,4 cycles of chemotherapy,and one,two,and three differences were: 5.573 ± 0.846,6.854 ± 0.820,3.136 ± 0.220,1.281 ± 0.438,2.438 ± 0.758,3.718 ± 0.659 ng / μl;the mean of ctDNA concentration before chemotherapy,after 2,4 cycles of chemotherapy,and the first,second and third cycles of SD group were: 5.455 ± 1.326,7.352 ± 1.237,4.466 ± 0.860,1.897 ± 0.751 0.988 ± 0.985,2.886 ± 0.826 ng / μl.In summary: the ctDNA concentration level after 4 cycles of chemotherapy in the PR group was significantly less than that in the SD group;the ctDNA concentration in both groups showed an upward trend after 2 cycles of chemotherapy,and there was no significant difference between the PR and SD groups;after 4 cycles of chemotherapy and before chemotherapy Compared with the ctDNA concentration after 2 cycles of chemotherapy,the ctDNA concentration of the two groups showed a downward trend,and the decrease was significantly greater in the PR group than in the SD group.3.There was no correlation between lung tumor regression rate and gender,age,smoking history and pathological classification of NSCLC patients.The concentration of ctDNA before chemotherapy was positively correlated with the maximum cross-sectional area of lung tumors before chemotherapy(r = 0.582,P = 0.004).There was no significant correlation between lung tumor regression rate and ctDNA concentration before chemotherapy.The regression rate was significantly negatively correlated with the ctDNA concentration after 2 cycles of chemotherapy and after 4 cycles of chemotherapy(r =-0.584,P = 0.004 after 2 cycles of chemotherapy;r =-0.922,P = 0.000 after 4 cycles of chemotherapy).Compared with the ctDNA concentration before chemotherapy,the increase in ctDNA concentration after 2 cycles of chemotherapy was negatively correlated with the regression rate(r=-0.499,P= 0.018);the decrease in ctDNA concentration after 4 cycles of chemotherapy was positively correlated with the regression rate(r= 0.511,P= 0.015).Compared with after 2 cycles of chemotherapy,ctDNA concentration decreased after 4 cycles of chemotherapy,and there was no significant correlation between the decrease and the regression rate.4.The general clinical characteristics(age,sex,smoking history,pathological type)of 22 NSCLC patients after chemotherapy were not statistically different between groups;the PFS mean level in the PR group was 10.57 ± 1.46,and the PFS mean level in the SD group Was 4.00 ± 1.60,the PFS mean level in the PR group was greater than that in the SD group,P= 0.000,the difference was statistically significant;the PFS mean level was 9.44 ± 2.47 in the chemotherapy high-response group,and the PFS mean level was 4.18 in the low-chemotherapy group.± 2.34,the mean level of PFS in the high-chemotherapy group was greater than that in the low-chemotherapy group,P= 0.000,the difference was statistically significant.Conclusion: 1.The ctDNA concentration level is positively correlated with the tumor burden of NSCLC;2.The change trend of ctDNA concentration is related to the efficacy of advanced NSCLC chemotherapy.Monitoring changes in ctDNA concentration during chemotherapy may predict the efficacy of chemotherapy early. |
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