Clinical Efficacy Of Radiotherapy Combined With Immunotherapy In Non-small Cell Lung Cancer Patients With Brain Metastases

Objective: This study aims to explore the clinical efficacy of radiation therapy combined with immunotherapy(PS: concurrent therapy refers to immunotherapy within4 weeks of the end of radiation therapy)in patients with brain metastases(BM)of non-small cell lung cancer(NSCLC)with central nervous system symptoms.Methods:The clinicopathological features of 54 patients with NSCLC-BM with definite clinical diagnosis of driver gene negative radiotherapy combined with immunotherapy presented in major hospitals of Inner Mongolia from September 2020 to December2022 were retrospectively collected,including name,sex,age,smoking or not,pathological type,ECOG score,number of brain metastases,etc.The time to confirmation of brain metastases,the initiation of radiothera Py and/or immunotherapy,and the MRI size of brain metastases at least 3 months before and at least 3 months after treatment were collected from all NSCLC-BM patients included in this study.According to the different treatment mode,it was divided into observation group radiotherapy combined with immunotherapy(the simultaneous radio-immuno therapy)and control group radiation therapy to the brain alone(radiotherapy alone).Later,patients were followed up at least once a month by telephone or inpatient or outpatient to assess the time of disease progression or recurrence.Evaluation of therapeutic effect was performed according to Solid Tumor Response Evaluation Criteria(RECIST)version1.1.The primary observed outcome were progression-free survival(PFS),and disease control rate(DCR),in addition objective response rate(ORR).Univariate and multivariate analysis of patient survival using the Kaplan-Meier method and Cox proportional hazards regression model,and comparison of differences between groups using log-rank test.All data were analyzed using SPSS 26.0 statistical software.All are P<0.05 was considered statistically significant.Results: 1.A total of 54 patients with NSCLC-BM were incorporated in this study,and the short-term therapeutic effect of the two regimens is as follows:In the simultaneous radio-immuno therapy group(N=27),DCR was 74.1%,ORR was 40.8%,and PFS was8.5 months;in the radiotherapy alone group(N=27),the DCR was 55.4%,ORR 27.7%,and PFS 4.8 months.The short-term therapeutic effect of the two treatment regimens was compared by chi-square test: DCR in the simultaneous radio-immuno therapy group was better than that in the radiotherapy alone group,and the difference was statistically significant(P<0.05).The ORR of the simultaneous radio-immuno therapy group was also better than that in the radiotherapy alone group,but the difference was not statistically significant(P>0.05).The long-term efficacy of PFS of the two treatment regimens was analyzed by Ka Plan-Meier method: PFS was 8.5 months(7.4-9.3)in the simultaneous radio-immuno therapy group and 4.8 months(4.2-5.4)in the radiotherapy alone group,with a statistically significant difference(P<0.05,X2=21.83).The results of univariate Log-rank test showed that treatment mode and ECOG score were related to survival outcome and survival time,and were predictors of whether patients had new intracranial lesions(P<0.05);The results of Cox multivariate survival analysis showed that treatment mode and ECOG score were also independent predictors of whether patients had new intracranial lesions(P<0.05).2.Adverse event analysis of treatment regimens:One patient in both groups developed radiation cerebral necrosis and the difference was not statistically significant(P>0.05).Grade 1-2 adverse events in both groups:The simultaneous radio-immuno therapy group was mainly manifested as loss of appetite(n=8),headache(n=7),hypothyroidism(n=7),fatigue(n=7),rash/itching(n=7),cerebral edema(n=6),nausea/vomiting(n=5),followed by hyponatremia(n=4)and liver damage(n=3).In the radiotherapy group alone,anorexia(n=6)and headache(n=5),followed by fatigue(n=4),nausea/vomiting(n=4),cerebral edema(n=3),hyponatremia(n=2),hypothyroidism(n=2),liver damage(n=1),and rash/pruritus(n=0).Grade 3-4 adverse events occurred in only 1 case of rash/pruritus in the radio-free group,and there was no significant difference between the two groups(P >0.05).Grade 1 to 2 adverse events were compared with no statistically significant difference between the incidence of nausea/vomiting,fatigue,loss of appetite,cerebral edema,headache,liver damage,and hyponatremia(P >0.05).Only the incidence of rash/pruritus and hypothyroidism was statistically significant(P = 0.002).Conclusions:1.Patients with driver-negative non-small cell lung cancer brain metastases receiving simultaneous radio-immuno therapy can prolong PFS and increase ORR and DCR.2.Patients with driver gene-negative non-small cell lung cancer brain metastases receiving simultaneous radio-immuno therapy can reduce the incidence of new intracranial lesions.