| Background:Brain metastases(Br Ms)are an important source of morbidity and mortality in patients with non-small cell lung cancer,about 25-30% of patients with advanced NSCLC are accompanied by brain metastasis when they are initially diagnosed.Meanwhile,40-50 % of patients will develops into brain metastasis during the course of disease.In recent years,many studies have confirmed that immune checkpoint inhibitors(ICIs)as the standard treatment that can improve the prognosis of advanced NSCLC patients with negative driver genes.Therefore,a retrospective study and analysis was conducted on the patients with advanced NSCLC with the real-world data,especially those with Brain metastases,to ensure that the treatment of intracranial progression free survival(i PFS)and improved quality of life would not be ignored.Objective:To observe the effect of immune checkpoint inhibitor combined with radiotherapy and chemotherapy in the treatment of brain metastases in non-small cell lung cancer.Methods:In this real-world study,we retrospectively analyzed patients that with driver-negative advanced NSCLC brain metastases who were received ICIs treatment at the Institute of Respiratory Health of Guangzhou Medical University from January2018 to January 2021.We also collected baseline data including age,gender,pathological type,systemic and local treatment status.They were divided into two groups based on whether immunotherapy was used.Experimental group received chemoradiotherapy and systemic immunotherapy,compared to patients without immune checkpoint inhibitor treatment,the baseline characteristics of two groups were compared at the same time.The primary endpoint was overall survival(OS),and the intracranial objective response rate(i ORR),disease control rate(DCR)and intracranial progression-free survival(i PFS)were secondary.Meanwhile,the safety of treatment and variety of neurological function were compared.The efficacy of immunotherapy was evaluated according to the Response Evaluation Criteria in Solid Tumors(RECIST)version 1.1.The statistical software was SPSS 25.0,and the measurement data were expressed as(Mean ± SD),using independent sample T test.The count data are expressed as [n(%)],using the 2 test.The survival rate was calculated by Kaplan-Meier method.P < 0.05 was considered statistically significant.Results:Among the 1632 cases of NSCLC admitted to Guangzhou Institute of Respiratory Health from January 2018 to January 2021,116 patients with driver gene-negative NSCLC brain metastases who met the inclusion and exclusion criteria were included in the study.Patients who received concurrent immunotherapy were defined as the observation group(n= 56),when the control group was patients who did not receive the immune checkpoint inhibitors treatment(n= 60).1.There was no significant difference in gender,age,smoking history and pathological type between the two groups(P > 0.05).2.The chemoradiotherapy patients treated with immune checkpoint inhibitors,27 patients achieved partial response,17 patients were stable disease,12 patients with progressive disease.The disease control rate was 78.57%.Among the control group,17 patients got partial response,14 patients were stable disease,when 29 patients were progressive disease,and the DCR was 51.67 %.Otherwise,none of the patients reached complete response.The disease control rate of the observation group was significantly higher than that of the control group,the differences between the two groups were statistically significant(c2 = 5.127,P= 0.024).3.The response of intracranial lesions between the two groups was as follows:There were 27 cases of intracranial objective remission in the observation group,and the i ORR was 48.21 %.There were 17 cases of objective remission in the control group,and the i ORR was 28.34 %(c2 = 2.226,P > 0.05).There was no statistical difference between the two groups.4.There was no significant difference in bone marrow suppression,gastrointestinal reactions,liver and kidney function,cardiac toxicity,alopecia and hemoptysis between the two groups(P > 0.05).5.The median overall survival in the observation group was 11.5 months(95 %CL: 8.68-14.32),which was significantly longer than the 8.2 months in the control group(95 %CL: 7.68 – 8.72)(χ2= 9.685,P < 0.05;HR: 0.421,95 %CL: 0.24– 0.74,P < 0.05),suggesting a survival benefit.In the observation group,the median survival time of patients with TPS score ≥1% was significantly longer than that of TPS score <1%(χ2= 12.884,P <0.05),which showed a statistically significant difference,indicating that the higher the TPS score,the more obvious the survival benefit.6.The results of intracranial progression-free survival in the two groups were as follows: the median i PFS in patients receiving immune checkpoint inhibitors was 10.3months(95 %CL: 8.42 – 12.18),better than the control group at 6.7 months(95 %CL: 6.02-7.38),(χ2= 13.725,P < 0.01;HR: 0.352;95 %CI 0.198-0.626;P< 0.01).In the observation group,the higher the TPS score,the longer the intracranial progression-free survival period(χ2= 18.181,P <0.05),the difference was statistically significant,suggesting that the TPS score may affect the intracranial response to immunotherapy.7.The proportion of neurological level 1 in the observation group was significantly higher than that of the control group,when the neurological level 5 was significantly lower than the control group(χ2= 4.278,P < 0.05).8.In the subgroup analysis,20 patients were treated with concurrent chemoradiotherapy and immunotherapy,and 36 patients were not.Statistical analysis showed that there was no significant difference in intracranial progression-free survival(8.97 months vs 8.60 months),intracranial objective response rate(50.00 %vs 47.22 %)and disease control rate(80.00 % vs 77.78 %)(P > 0.05).Conclusion:The results of this real-world study showed that on the basis of concurrent chemoradiotherapy,the addition of ICIs treatment could improve the intracranial progression-free survival time,median survival time and i DCR of patients with driver gene-negative NSCLC brain metastasis,without increasing adverse reactions,prolonging survival time and improving neurological function.The effect may be associated with the TPS level in the patients.The comparison of concurrent immunotherapy and nonconcurrent chemoradiotherapy may have higher survival benefit and clinical control rate.Based on its adverse effects,the optimal time of combining immunotherapy and chemoradiotherapy still needs to be further explored. |
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