| ObjectiveIn this study,we analyzed the prognostic nutritional index(PNI),albumin to globulin ratio(AGR),carcinoembryonic antigen(CEA),and cytokeratin 19 fragment(CYFRA21-1)of patients with advanced non small cell lung cancer before immunotherapy to evaluate the efficacy and prognosis of different immunotherapy regimens,so as to screen out the population with superior immune response.MethodsA total of 128 patients with advanced non-small cell lung cancer who met the admission criteria in the Department of Respiratory and Critical Care Medicine of our hospital from January 2020 to January 2022 were collected.Their general data,laboratory indicators,and chest CT were collected.The optimal cutoff values of PNI,AGR,CEA,and CYFRA21-1 before immunotherapy were determined based on the receiver operating characteristic curve(ROC)and area under the curve(AUC)of the subject.The above indicators were divided into high PNI(H-PNI)group and low PNI(L-PNI)group based on the optimal cutoff values;High AGR(H-AGR)group,low AGR(L-AGR)group;High CEA(H-CEA)group,low CEA(L-CEA)group;High CYFRA21-1(H-CYFRA21-1)group,low CYFRA21-(LCYFRA21-1)group.For efficacy evaluation,refer to the Solid Tumor Efficacy Evaluation Standard(RECIST)1.1,and compare the differences in objective response rate(ORR)and disease control rate(DCR)of patients in each group through chi-square test.The Kaplan Meier method was used to conduct a single factor survival analysis and draw a survival curve.The differences between the groups were analyzed and compared using a log rank test.The statistically significant factors in the single factor analysis were included in the Cox proportional regression model for multivariate analysis.All statistical analyses were performed using SPSS26.0 software,with P<0.05 representing a statistically significant difference.Result1.Relationship between general clinical characteristics of patients and the efficacy of immunosuppressive therapyThe DCR of patients aged>68 years(34.3%)was significantly lower than that of patients aged<68 years(59.0%)(P=0.005).The ORR of patients in the immuno combined chemotherapy group(34.8%)was higher than that in the immuno single drug group(17.7%),with a statistically significant difference(P=0.029).The DCR of patients in the immuno combined chemotherapy group(56.1%)was higher than that of patients in the immuno single drug group(35.5%),with a statistically significant difference(P=0.020).The ORR of patients receiving first line immunotherapy(37.5%)was higher than that of patients receiving second line immunotherapy(18.1%),with a statistically significant difference(P=0.013).The DCR of patients receiving first line immunotherapy(58.9%)was higher than that of patients receiving second line immunotherapy(36.1%),with a statistically significant difference(P=0.010).2.Relationship between peripheral blood indicators and the efficacy of immunosuppressive therapy2.1.The influence of peripheral blood parameters on the efficacy of patients in the first-line immunotherapy subgroupIn the population of first-line immunotherapy patients,there was no statistically significant difference in ORR and DCR among PNI,AGR,CEA,and CYFRA21-1 groups(P>0.05),and no significant predictive value was found for the efficacy of immunotherapy.2.2.The influence of peripheral blood parameters on the efficacy of patients in the second line immunotherapy subgroup.The ORR of patients in the H-PNI group(26.9%)was higher than that in the L-PNI group(0.0%),with a statistically significant difference(P=0.035).The DCR of patients in the H-PNI group(46.2%)was also higher than that of patients in the L-PNI group(13.3%),with a statistically significant difference(P=0.033).The ORR of patients in the H-AGR group(38.5%)was higher than that in the L-AGR group(7.1%),with a statistically significant difference(P=0.024).The DCR of patients in the H-AGR group(61.5%)was higher than that in the L-AGR group(21.4%),with a statistically significant difference(P=0.030).The ORR of patients in the H-CEA group(10.7%)was lower than that in the L-CEA group(30.8%),with no statistically significant difference(P=0.181).However,the ORR of patients in the L-CEA group showed a good trend.The DCR of patients in the H-CEA group(21.4%)was significantly lower than that in the L-CEA group(61.5%)(P=0.030).The ORR(0.0%)of patients in the H-CYFRA21-1 group was significantly lower than that in the L-CYFRA21-1 group(30.4%),with a statistically significant difference(P=0.012).The DCR(5.6%)of patients in the H-CYFRA21-1 group was significantly lower than that in the L-CYFRA21-1 group(56.5%),with a statistically significant difference(P=0.001).2.3.Effect of peripheral blood indicators on the efficacy of first-line immunotherapy combined with chemotherapy in subgroups of patientsThe ORR of patients in the H-AGR group(66.7%)was significantly higher than that in the L-AGR group(21.4%),with a statistically significant difference(P=0.009).The DCR of patients in the H-AGR group(90.5%)was significantly higher than that of patients in the LAGR group(42.9%),with a statistically significant difference(P=0.008).The DCR of patients in the H-CEA group(52.9%)was significantly lower than that in the L-CEA group(88.9%)(P=0.048).Although there was no significant difference in ORR among patients with different CEA groups(P>0.05),the ORR of patients with L-CEA group was higher than that of patients with H-CEA group.The ORR of patients in the H-CYFRA21-1 group(23.1%)was significantly lower than that of patients in the L-CYFRA21-1 group(63.6%),with a statistically significant difference(P=0.020).The DCR of patients in the H-CYFRA21-1 group(53.8%)was lower than that of patients in the L-CYFRA21-1 group(81.8%),with no statistically significant difference(P=0.167).2.4.Effect of peripheral blood markers on the efficacy of second line immunochemotherapy in subgroups of patientsThe ORR(0.0%)of patients in the H-CYFRA21-1 group was significantly lower than that of patients in the L-CYFRA21-1 group(37.5%),with a statistically significant difference(P=0.018).The DCR of patients in the H-CYFRA21-1 group(20.0%)was significantly lower than that of patients in the L-CYFRA21-1 group(56.3%),with a statistically significant difference(P=0.038).3.The relationship between the general clinical characteristics and peripheral blood indicators of patients and the prognosis of immunosuppressive therapyThe Kaplan-Meier univariate survival analysis of patients’ general clinical characteristics,peripheral blood indicators,and PFS showed that the median PFS(6.74 months)of patients aged 68 years or older was significantly lower than the median PFS(10.99 months)of patients aged less than 68 years,with a statistically significant difference(P=0.012).The median PFS of patients with metastatic sites less than 3(8.99 months)was superior to that of patients with metastatic sites greater than or equal to 3(5.36 months),with a statistically significant difference(P=0.036).The median PFS of patients receiving first line immunotherapy(10.02 months)was longer than that of patients receiving second line immunotherapy(7.40 months),with a statistically significant difference(P=0.047).The median PFS(10.99 months)of patients in the immuno combined chemotherapy group was significantly higher than that of patients in the immuno single drug group(6.74 months),with a statistically significant difference(P=0.010).The median PFS of patients in the H-PNI group(10.99 months)was longer than the median PFS of patients in the L-PNI group(5.95 months),with a statistically significant difference(P=0.000).The median PFS of patients in the H-AGR group was not reached,while the median PFS of patients in the L-AGR group was 6.10 months,with a statistically significant difference(P=0.000).The median PFS of patients in the H-CEA group was 6.05 months,while the median PFS of patients in the L-CEA group was not achieved,with a statistically significant difference(P=0.000).The median PFS of patients in the HCYFRA21-1 group was 5.36 months,and the median PFS of patients in the L-CYFRA21-1 group was not achieved,with a statistically significant difference(P=0.000).Inclusion of meaningful indicators from Kaplan Meier’s univariate survival analysis into COX multivariate regression analysis showed that PNI≥42.95(HR:0.510,95%CI:0.311～0.834,P=0.007),AGR≥ 1.31(HR:0.401,95%CI:0.215～0.748,P=0.004)could be independent positive predictors of PFS,and distant metastasis sites≥3(HR:2.600,95%CI:1.303～5.186,P=0.007),CEA ≥ 4.71(HR:1.886,95%CI:1.045～3.402,P=0.035),CYFRA21-1≥ 5.32(HR:1.950,95%CI:1.167～3.259,P=0.011)can be used as an independent negative predictor of PFS.Conclusion1.The efficacy and prognosis of patients treated with immuno combined chemotherapy were better than those treated with immuno single drug therapy;The efficacy and prognosis of patients receiving first line immunotherapy are better than those receiving second line immunotherapy;Patients younger than 68 years of age benefit more from immunotherapy.Patients with distant metastases less than 3 have a better prognosis.2.Pre treatment PNI,AGR,CEA,and CYFRA21-1 can serve as potential predictive markers for the efficacy and prognosis of immunotherapy in advanced non-small cell lung cancer patients.(1)Patients in the H-AGR,L-CEA,and L-CYFRA21-1 groups who received first-line immunochemotherapy had better therapeutic effects before treatment.(2)Patients in the L-CYFRA21-1 group who received second line immunotherapy combined with chemotherapy had better efficacy before treatment.(3)Patients in the H-PNI,H-AGR,L-CYFRA21-1,and L-CEA groups who received secondline immunotherapy with a single drug had better efficacy before treatment.(4)Pre treatment H-PNI,H-AGR,L-CYFRA21-1,L-CEA are all associated with better prognosis.3.PNI≥42.95 and AGR≥1.31 before immunotherapy can serve as independent prognostic factors for PFS in NSCLC patients after ICI treatment.The number of distant metastatic sites≥ 3,CEA≥ 4.71,and CYFRA21-1≥ 5.32 can serve as independent prognostic factors for poor PFS in NSCLC patients after ICI treatment. |
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