Efficacy And Safety Of Radiation In Combination With Immune Checkpoint Inhibitors For Melanoma Brain Metastases:A Meta-analysis

Objective:We conducted a meta-analysis to assess the clinical efficacy and the incidence of radiation necrosis in melanoma brain metastases patients receiving radiation and ICIs.Methods:The databases(Embase,Pub Med,Cochrane,Google Scholar and Web of Science)were searched from the inception to September 2019.The Meta-analysis was performed by Rev Man 5.3 software.Combined HR and 95%CIs were calculated for overall survival and intracranial progression.Combined OR and 95%CIs were calculated for the incidence of RN.According to the heterogeneity,fixed effects model or random effects model was used.Funnel and Begg’s test analysis were used for potential publication bias.Results:1、We have initially identified 365 studies through the above database.A total of 16 studies meet the requirement and a total of 3936 patients were included.In the radiotherapy combined with ICIs group,the longest overall survival time was 24.0 months,the shortest was 7.4 months,and the median overall survival time was 15.0 months.In the radiation therapy group,the longest overall survival time was 19.7 months,the shortest was 2.29months,and the median overall survival time was 6.2 months.2、Meta-analysis results showed that radiation and ICIs group improved overall survival when compared to radiation group alone(HR=0.42,95%CI:0.36-0.48,p<0.05)with a high heterogeneity(I~2=57.6%).Subgroup analysis results shows that radiation and anti-CTLA-4improved overall survival(HR=0.35,95%CI:0.26-0.44,p<0.05).The effect of concurrent treatment is better than non-current treatment(HR=0.18,95%CI:0.03-0.33,p<0.05).3、Compared with radiation group alone,radiation and ICIs group reduced the risk of intracranial progression(HR=0.49,95%CI:0.20-0.77,p<0.05)with a low heterogeneity(I~2=0.0%).4、The risk of RN in radiation and ICIs group was 4.99(95%CI:2.31-10.78,p<0.05)times that of the radiation group with a low heterogeneity(I~2=0.0%).Conclusion:Radiation combined ICIs treatment prolonged the overall survival and reduced the risk of intracranial progression.It also increased the risk of radiation necrosis for melanoma brain metastases patients,which requires great attention.