Efficacy And Possible Mechanism Of Carrelizumab Combined With Radiotherapy And Chemotherapy In Locally Advanced Non-squamous Non-small Cell Lung Cancer

BackgroundThe incidence and mortality of lung cancer are in the first place of malignant tumors.The most common type of lung cancer is non-small cell lung cancer（NSCLC）.Most patients are in the middle and advanced stage when diagnosed,and the overall prognosis is poor.Lung cancer is usually treated by surgery,radiotherapy,chemotherapy,targeted therapy,immunotherapy,etc.The continuous development of biological agents such as targeted therapy and immunotherapy brings hope for the increased survival of patients with advanced lung cancer.Currently,the efficacy and possible mechanism of the independently developed PD-1 inhibitor carrelizumab combined with chemoradiotherapy for locally advanced non-squamous NSCLC have not been reported.This study will explore the effect of selecting carrelizumab combined with concurrent chemoradiotherapy for locally advanced non-squamous NSCLC patients,providing new ideas for clinical diagnosis and treatment.ObjectiveThis research goal is to investigate the condition of carrelizumab combined with simultaneous intensive-modulated radiotherapy（SIB-IMRT）with pemetrexed disodium and cisplatin in patients with locally advanced driving gene-negative non-squamous non-small cell lung cancer（NSCLC）during treatment,and to explore its possible mechanism of action.MethodsIn this study,patients with local NSCLC admitted to Zhumadian Central Hospital from July 2019 to December 2020 were randomly divided into two groups.The former was the control group and the latter was the study group.Ensure that all kinds of data of patients in the process of treatment are complete,and comprehensively analyze the physical condition of patients in the process of treatment.In the control group,patients were treated with SIB-IMRT combined with pemetrexed disodium and cisplatin.The dose of intrapulmonary tumor tissue（GTV-T）and metastatic lymph node（GTV-N）was 66Gy/30F,the clinical target area（CTV）was 0.8cm on the basis of gross tumor target area（GTV）,the CTV dose was 60Gy/30F,and the planned target area（PTV）was 0.5cm on the basis of CTV;The patient received systemic chemotherapy on the first day.500 mg/m~2d₁pemetrexed and 20 mg/m~2d_1-5cisplatin were selected for chemotherapy.One chemotherapy cycle was 27 days.The patient needed a total of 4 cycles of chemotherapy.The study group was based on the premise of drugs and chemotherapy in the control group.The patients were treated with carrelizumab immunotherapy every day with a dose of 200 mg/time d₀,once every 27 days.After chemotherapy,the patients were treated with carrelizumab immunotherapy every 27 days until there were new changes in the patient’s condition or the patient could not tolerate it.At this time,the use of such drugs could be abandoned,Improve the quality of life of patients.In the course of treatment,patients selected the terminology standard for adverse reactions version 4.0 for evaluation.After chemotherapy,the levels of CD3⁺,CD4⁺,CD8⁺and CD4⁺/CD8⁺in peripheral blood T lymphocytes were detected by flow cytometry and IL-2,IL-10 and IFN-γwere detected by enzyme-linked immunosorbent assay（ELISA）;The chest,abdomen and pelvis enhanced CT,serum tumor markers（CEA,NSE,CYFRA21-1,CA125 and SCC）were detected again.The curative effect was evaluated according to the solid tumor curative effect evaluation standard version 1.1（RECIST 1.1）.The objective remission rate（ORR）,disease control rate（DCR）,median progression free survival（PFS）,median overall survival（OS）and 1-year survival rate of the two groups were observed.Results1.Hematology and liver and kidney function tests of patients in the two groups:there was no statistical significance in the comparison of the contents of white blood cells,neutrophils,hemoglobin and platelets between the two groups before treatment.There was no statistical significance in BUN and Cr between the two groups before and after treatment.ALT,AST and TBIL in the study group were higher than those in the control group after treatment,and The difference was statistically significant（P<0.05）.2.Disease control rate,quality of life and survival of patients in the two groups:After treatment,the ORR and DCR in the study group were significantly higher than those in the control group,with significant differences（P<0.05）,indicating statistically significant differences.After treatment,KPS and QOL scores were significantly improved in both groups.After treatment,both scores in the study group were higher than those in the control group,and the difference was statistically significant（P<0.05）.The m PFS,m OS and 1-year survival rate of patients in the study group were significantly higher than those in the control group,and the differences were statistically significant（P<0.05）.3.The incidence of adverse reactions in the two groups during treatment:the incidence of bone marrow suppression,gastrointestinal reaction,fatigue,anemia and hypertension in the study group was significantly different from that in the control group（P>0.05）,and the difference was not statistically significant.The incidence of abnormal liver function,reactive capillary hyperplasia and hypothyroidism in the study group was significantly higher than that in the control group,and the difference was statistically significant（P<0.05）.4.Serological and peripheral blood examination before and after treatment:After treatment,The IL-2,IFN-γ,CD3⁺,CD4⁺and CD4⁺/CD8⁺ratio in the study group were higher than those in the control group,while IL-10 and CD8⁺were lower than those in the control group.After treatment,serum tumor markers CEA,NSE,CYFRA21-1,CA125 and SCC in the study group were lower than those in the control group（P<0.05）,the difference was statistically significant.Conclusion1.Carrelizumab combined with SIB-IMRT combined with pemetrexed disodium and cisplatin can greatly improve ORR and DCR,increase survival time and tolerable side effects in patients with locally advanced driver gene negative non squamous NSCLC.It can improve the quality of life of patients with significant clinical effects.2.The mechanism of carrelizumab combined with SIB-IMRT combined with pemetrexed disodium and cisplatin in the treatment of locally advanced non-NSCLC patients with negative driver gene may be to increase the expression levels of IL-2,IFN-γand CD3⁺,CD4⁺and CD4⁺/CD8⁺ratio and decrease the expression levels of IL-10 and CD8⁺Flat.