Abstract：
BACKGROUND: The association between SWI/SNF genomic alterations and responses to immune checkpoint inhibitors (ICIs) remains conflicting. This meta-analysis was performed to systematically assess the impact of SWI/SNF genomic alterations on response to ICIs in cancer.
METHODS: Relevant studies were searched in multiple databases updated to April 29, 2021. Outcomes of interest included prevalence of SWI/SNF alterations, overall survival (OS), progression-free survival (PFS) and time to treatment failure (TTF). For survival data, the hazard ratio (HR) was adopted, and the effect size was described as 95% confidence intervals (CI).
RESULTS: 15 studies involving 10,849 patients were included, with the overall frequency of 18.5% in SWI/SNF alterations. Across different cancer types, the mutational frequency of PBRM1 (32.0%) was the highest, followed by ARID1A (18.1%), SMARCA4 (15.6%), SMARCA2 (10.3%), ARID2 (8.1%), SMARCC2 (6.4%) and SMARCB1 (5.0%). Overall analysis showed that SWI/SNF alterations were not associated with improved OS (HR: 0.822, 95 %CI: 0.583-1.158, p = 0.262), PFS (HR: 0.608, 95 %CI: 0.434-1.067, p = 0.094) and TTF (HR: 0.923, 95 %CI: 0.757-1.125, p = 0.427) in patients treated with ICIs. In subgroup analysis, PBRM1 mutations were observed to be linked with improved OS (HR: 0.650, 95 %CI: 0.440-0.960, p = 0.030), PFS (HR: 0.539, 95 %CI: 0.314-0.926, p = 0.025) and TTF (HR: 0.490, 95 %CI: 0.271-0.885, p = 0.018) in RCC patients receiving ICIs.
CONCLUSIONS: The overall prevalence of SWI/SNF alterations was 18.5% across different cancer types. Except for PBRM1 mutations in RCC, SWI/SNF alterations may be uncorrelated with improved clinical outcomes in cancer.
METHODS: Relevant studies were searched in multiple databases updated to April 29, 2021. Outcomes of interest included prevalence of SWI/SNF alterations, overall survival (OS), progression-free survival (PFS) and time to treatment failure (TTF). For survival data, the hazard ratio (HR) was adopted, and the effect size was described as 95% confidence intervals (CI).
RESULTS: 15 studies involving 10,849 patients were included, with the overall frequency of 18.5% in SWI/SNF alterations. Across different cancer types, the mutational frequency of PBRM1 (32.0%) was the highest, followed by ARID1A (18.1%), SMARCA4 (15.6%), SMARCA2 (10.3%), ARID2 (8.1%), SMARCC2 (6.4%) and SMARCB1 (5.0%). Overall analysis showed that SWI/SNF alterations were not associated with improved OS (HR: 0.822, 95 %CI: 0.583-1.158, p = 0.262), PFS (HR: 0.608, 95 %CI: 0.434-1.067, p = 0.094) and TTF (HR: 0.923, 95 %CI: 0.757-1.125, p = 0.427) in patients treated with ICIs. In subgroup analysis, PBRM1 mutations were observed to be linked with improved OS (HR: 0.650, 95 %CI: 0.440-0.960, p = 0.030), PFS (HR: 0.539, 95 %CI: 0.314-0.926, p = 0.025) and TTF (HR: 0.490, 95 %CI: 0.271-0.885, p = 0.018) in RCC patients receiving ICIs.
CONCLUSIONS: The overall prevalence of SWI/SNF alterations was 18.5% across different cancer types. Except for PBRM1 mutations in RCC, SWI/SNF alterations may be uncorrelated with improved clinical outcomes in cancer.
摘要：
背景：SWI/SNF基因组改变和对免疫检查点抑制剂（ICIs）的反应之间的关联仍然是矛盾的。进行该荟萃分析以系统地评估SWI/SNF基因组改变对癌症中ICI应答的影响。
方法：在更新至2021年4月29日的多个数据库中检索相关研究。感兴趣的结果包括SWI/SNF改变的患病率，总生存期（OS），无进展生存期（PFS）和治疗失败时间（TTF）。对于生存数据，采用了危险比(HR)，效应大小描述为95%置信区间(CI)。
结果：包括10,849名患者的15项研究，SWI/SNF改变的总频率为18.5%。在不同的癌症类型中，PBRM1的突变频率最高(32.0%),其次是ARID1A（18.1%），SMARCA4（15.6%），SMARCA2（10.3%），ARID2（8.1%），SMARCC2（6.4%）和SMARCB1（5.0%）。总体分析显示SWI/SNF改变与OS改善无关(HR:0.822,95CI:0.583-1.158,p=0.262),使用ICIs治疗的患者的PFS（HR：0.608，95CI：0.434-1.067，p=0.094）和TTF（HR：0.923，95CI：0.757-1.125，p=0.427）。在亚组分析中，观察到PBRM1突变与OS改善有关（HR：0.650，95CI：0.440-0.960，p=0.030），接受ICI的RCC患者的PFS（HR：0.539，95CI：0.314-0.926，p=0.025）和TTF（HR：0.490，95CI：0.271-0.885，p=0.018）。
结论：在不同癌症类型中，SWI/SNF改变的总体患病率为18.5%。除了RCC中的PBRM1突变，SWI/SNF改变可能与癌症改善的临床结果无关。
方法：在更新至2021年4月29日的多个数据库中检索相关研究。感兴趣的结果包括SWI/SNF改变的患病率，总生存期（OS），无进展生存期（PFS）和治疗失败时间（TTF）。对于生存数据，采用了危险比(HR)，效应大小描述为95%置信区间(CI)。
结果：包括10,849名患者的15项研究，SWI/SNF改变的总频率为18.5%。在不同的癌症类型中，PBRM1的突变频率最高(32.0%),其次是ARID1A（18.1%），SMARCA4（15.6%），SMARCA2（10.3%），ARID2（8.1%），SMARCC2（6.4%）和SMARCB1（5.0%）。总体分析显示SWI/SNF改变与OS改善无关(HR:0.822,95CI:0.583-1.158,p=0.262),使用ICIs治疗的患者的PFS（HR：0.608，95CI：0.434-1.067，p=0.094）和TTF（HR：0.923，95CI：0.757-1.125，p=0.427）。在亚组分析中，观察到PBRM1突变与OS改善有关（HR：0.650，95CI：0.440-0.960，p=0.030），接受ICI的RCC患者的PFS（HR：0.539，95CI：0.314-0.926，p=0.025）和TTF（HR：0.490，95CI：0.271-0.885，p=0.018）。
结论：在不同癌症类型中，SWI/SNF改变的总体患病率为18.5%。除了RCC中的PBRM1突变，SWI/SNF改变可能与癌症改善的临床结果无关。
