Willis Connor, Fiander Michelle, Tran Dao, Korytowsky Beata, Thomas John-Michael, Calderon Florencio, Zyczynski Teresa M, Brixner Diana, Stenehjem David D
Department of Pharmacotherapy, University of Utah, Salt Lake City, UT, USA.
Department of Pharmacy Practice and Pharmaceutical Sciences, University of Minnesota, Duluth, MN, USA.
Oncotarget. 2019 Nov 12;10(61):6604-6622. doi: 10.18632/oncotarget.27287.
To assess the association of tumor mutational burden (TMB) with clinical outcomes, other biomarkers and patient/disease characteristics in patients receiving therapy for lung cancer. In total, 4,303 publications were identified; 81 publications were included. The majority of publications assessing clinical efficacy of immunotherapy reported an association with high TMB, particularly when assessing progression-free survival and objective response rate. High TMB was consistently associated with alterations, and negatively associated with EGFR mutations. High TMB was also associated with smoking, squamous cell non-small cell lung carcinoma, and being male. A systematic literature review based upon an a priori protocol was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Cochrane methodologies. Searches were conducted in EMBASE, SCOPUS, Ovid MEDLINE, and Emcare (from January 2012 until April 2018) and in two clinical trial registries. Conference abstracts were identified in EMBASE, and in targeted searches of recent major conference proceedings (from January 2016 until April 2018). Publications reporting data in patients receiving therapy for lung cancer that reported TMB and its association with clinical efficacy, or with other biomarkers or patient/disease characteristics, were included. Results are presented descriptively. This systematic literature review identified several clinical outcomes, biomarkers, and patient/disease characteristics associated with high TMB, and highlights the need for standardized definitions and testing practices. Further studies using standardized methodology are required to inform treatment decisions.
为评估接受肺癌治疗患者的肿瘤突变负荷（TMB）与临床结局、其他生物标志物以及患者/疾病特征之间的关联。总共识别出4303篇出版物；纳入了81篇出版物。大多数评估免疫治疗临床疗效的出版物报告了与高TMB的关联，尤其是在评估无进展生存期和客观缓解率时。高TMB始终与改变相关，且与EGFR突变呈负相关。高TMB还与吸烟、鳞状细胞非小细胞肺癌以及男性相关。按照系统评价和Meta分析的首选报告项目（PRISMA）和Cochrane方法，基于预先制定的方案进行了系统文献综述。在EMBASE、SCOPUS、Ovid MEDLINE和Emcare（从2012年1月至2018年4月）以及两个临床试验注册库中进行了检索。在EMBASE以及近期主要会议论文集的定向检索（从2016年1月至2018年4月）中识别会议摘要。纳入报告接受肺癌治疗患者数据且报告了TMB及其与临床疗效、或与其他生物标志物或患者/疾病特征关联的出版物。结果采用描述性呈现。本系统文献综述确定了与高TMB相关的几种临床结局、生物标志物以及患者/疾病特征，并强调了标准化定义和检测方法的必要性。需要使用标准化方法进行进一步研究以指导治疗决策。
