Objective To evaluate the effects of sequential immunotherapy with radiotherapy on survival time and immune function in patients with unresectable stage Ⅲ non-small cell lung cancer(NSCLC)in a real-world study.Methods Data of 84 patients with unresectable stage Ⅲ NSCLC who were treated at the Affiliated Hospital of Inner Mongolia Medical University from January 2021 to December 2022(retrospective cohort)and from January 2023 to December 2023(prospective cohort)were collected.The patients were divided into the combination group(n=40)and radiotherapy group(n=44)based on whether they received sequential immunotherapy or not.The progression-free survival(PFS)and overall survival(OS)between two groups were compared using standardized mortality ratio weighting(SMRW).Univariate Cox proportional hazards model,multivariate regression analysis,multi-model comparison of propensity score matching and subgroup analysis were emploed to analyze the robustness of clinical efficacy between two groups.E-value analysis was used to analyze the sensitivity of unmeasured confounding factors in observational studies.Additionally,the percentage of CD4+T cells,CD8+T cells and natural killer(NK)cells,and CD4+/CD8+T cell ratio before and after treatment between two groups were compared using analysis of covariance.Results Among 84 patients,77(92％)cases were male and 7(8％)were female.Among them,42(50％)were aged 65 years or older.The variables showed high homogeneity after SMRW,with a standardized mean difference of less than 0.1.In the combination group,the median PFS[17.0 months vs.7.0 months,HR=0.260,95％CI:0.130-0.490,P＜0.001]and OS[not reached vs.24.0 months,HR=0.210,95％CI:0.070-0.590,P=0.002]were significantly longer compared to that in the radiotherapy group,with statistically significant differences.The study results were confirmed by robustness and sensitivity analyses.After treatment,patients in the combination group showed a statistically significant increase in the percentage of CD4+T cells and NK cells,and CD4+/CD8+T cell ratio,as well as a decrease in the percentage of CD8+T cells compared to those in the radiotherapy group(all P＜0.05).Conclusions Sequential immunotherapy following radiotherapy can significantly improve survival and prognosis of unresectable stage Ⅲ NSCLC patients.The survival benefit is even greater when combined with chemotherapy.The main mechanism of the survival benefit may be the improvement of anti-tumor immune function.
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