Analysis Of Clinical Factors Influencing MPR Of Neoadjuvant Immunotherapy For Potential Resectable Non-small Cell Lung Cancer

Objective:Investigating the clinical factors influencing the major pathologic response（MPR）of neoadjuvant immunotherapy for potential resectable non-small cell lung cancer（NSCLC）will contribute to predict the prognosis assessment in patients with NSCLC.Methods:A retrospective analysis was performed on the clinical data of 19 patients enrolled in a single-arm,phase II trial of Neoadjuvant PD-1 inhibitor（Sintilimab）combining with chemotherapy（nab-paclitaxel and carboplatin）in potential resectable stage III NSCLC（registration number:NCT04326153）in the Cancer Center of the First Hospital of Jilin University from December 2019 to November 2021.Gender,age,body mass index（BMI）,smoking history,TNM stage,gene mutation status,programmed cell death-ligand 1（PD-L1）expression status,hematology and imaging examination before neoadjuvant therapy,and pathological remission rate after surgery were included.All enrolled patients received 2-4 cycles of neoadjuvant immunotherapy treatment（Sintilimab+nanoparticle albumin-bound（nab-）paclitaxel+carboplatin）prior to surgery.Radical surgery was performed within 4 weeks after the end of treatment.All cases were followed up until January 31,2021.Patients were divided into MPR group and non-MPR group according to the pathological response rate of tumor tissue resection after surgery.All data were analyzed by SPSS 25.0statistical software,and the counting data is expressed as a percentage.Pearson Chi-square test or Fisher’s exact probability method was used for comparison between the two groups.The Kolmogorov-smirnov method was used to test the normality of measurement data,and the data conforming to normal distribution was expressed as mean±standard deviation（±s）.Independent sample T test was used for comparison between the two groups.The median（inter-quartile range）M(P₂₅,P₇₅)was used to represent the data that did not conform to normal distribution.The correlation between single factor and MPR was analyzed in the variables with P<0.05.Comparison between the two groups was performed by Mann-Whitney U test.Multivariate binary Logistic was worked in stepwise regression analysis.Only variables with P<0.05 in the univariate analysis and related variables verified in previous studies were included in the analysis.Odds ratio（OR）and 95%confidence interval（CI）were calculated.The receiver operating characteristic（ROC）curve was drawn,and the area under the curve（AUC）,sensitivity,specificity and Youden index were calculated.The variable value corresponding to the maximum Youden index was the optimal truncation value,can be used to screen out the ideal prediction factors.Results:1.A total of 19 patients with NSCLC were included in this study,including 15patients who underwent surgery after successfully completing neoadjuvant immunotherapy,including 9 patients in the MPR group（60%）and 6 patients in the non-MPR group（40%）.2.Univariate analysis showed that the expression level of PD-L1 in tumor tissues was correlated with MPR after neoadjuvant immunotherapy,and MPR group was higher than non-MPR group.Compared with non-MPR group,MPR group had lower platelet level,and the differences were statistically significant（p<0.05）.3.Multivariate logistics regression analysis showed that the level of PD-L1expression before treatment was an independent influence factor on MPR of potential resectable NSCLC after neoadjuvant immunotherapy（p<0.05）.4.Platelet count was negatively correlated with MPR.Pd-l1 expression level was positively correlated with MPR before treatment,with correlation coefficient R=0.642,indicating a strong correlation（p<0.05）.5.Plotting CD8+T cell level and PD-L1 expression level of tumor tissue before treatment receiver operating curve（ROC）can be obtained as follows:The AUC value of CD8+T cell level is 0.704（95%CI:0.435-0.973）,and the sensitivity and specificity were 55.6%and 83.3%when the optimal cut-off value was 30.53.The AUC value before p D-L1 treatment is 0.806（95%CI:0.435-0.973）,and the sensitivity and specificity were 100%and 50%when the optimal truncation value was>0.85%（p<0.05）.Conclusions:1.The MPR rate of sintilimab combined with nab-paclitaxel and carboplatin neoadjuvant immunotherapy for potential resectable NSCLC was 60%.2.PD-L1 expression level and platelet count level in NSCLC tumor tissue before treatment may be associated with MPR after neoadjuvant immunotherapy.PD-L1expression level was an independent predictor.3.CD8+T cell level in vivo before treatment and PD-L1 expression level in tumor tissue before neoadjuvant immunotherapy were ideal predictors of MPR.