Johns Hopkins University, Baltimore, MD.
Genentech Inc, South San Francisco, CA.
JCO Glob Oncol. 2021 Sep;7:1537-1546. doi: 10.1200/GO.21.00309.
In patients with advanced non-small-cell lung cancer (aNSCLC), tumor mutational burden (TMB) may vary by genomic ancestry; however, its impact on treatment outcomes is unclear. This retrospective, observational study describes treatment patterns of patients with aNSCLC by genomic ancestry and electronic health record (EHR)-reported race and/or ethnicity and evaluates differences in TMB, cancer immunotherapy (CIT) access, and treatment outcomes across racial and ancestral groups.
Patients diagnosed with aNSCLC after January 1, 2011, were selected from a real-world deidentified clinicogenomics database and EHR-derived database; continuously enrolled patients were evaluated. Race and/or ethnicity was recorded using variables from the EHR database; genomic ancestry was classified by single-nucleotide polymorphisms on a next-generation sequencing panel. A threshold of 16 mutations per megabase was used to categorize TMB status.
Of 59,559 patients in the EHR-derived database and 7,548 patients in the clinicogenomics database, 35,016 (58.8%) and 4,392 (58.2%) were continuously enrolled, respectively. CIT use was similar across EHR-reported race groups, ranging from 34.4% to 37.3% for non-Hispanic Asian and non-Hispanic Black patients, respectively. TMB levels varied significantly across ancestry groups ( < .001); patients of African ancestry had the highest median TMB (8.75 mutations per megabase; interquartile range, 4.35-14.79). In patients who had received CIT, high TMB was associated with improved overall survival compared with low TMB (20.89 11.83 months; hazard ratio, 0.60; 95% CI, 0.51 to 0.70) across genomic ancestral groups.
These results suggest that equitable access to next-generation sequencing may improve aNSCLC outcome disparities in racially and ancestrally diverse populations.
在晚期非小细胞肺癌（aNSCLC）患者中，肿瘤突变负担（TMB）可能因基因组起源而异；然而，其对治疗结果的影响尚不清楚。这项回顾性观察研究描述了根据基因组起源以及电子健康记录（EHR）报告的种族和/或族裔划分的 aNSCLC 患者的治疗模式，并评估了不同种族和祖裔群体之间 TMB、癌症免疫治疗（CIT）的可及性以及治疗结果的差异。
从真实世界的无标识临床基因组学数据库和 EHR 衍生数据库中选择 2011 年 1 月 1 日以后诊断为 aNSCLC 的患者；连续入组的患者进行了评估。种族和/或族裔使用 EHR 数据库中的变量进行记录；基因组起源通过下一代测序面板上的单核苷酸多态性进行分类。使用 16 个突变/兆碱基的阈值来分类 TMB 状态。
在 EHR 衍生数据库中的 59559 例患者和临床基因组学数据库中的 7548 例患者中，分别有 35016（58.8%）和 4392（58.2%）例患者连续入组。EHR 报告的种族组之间 CIT 的使用情况相似，非西班牙裔亚裔患者的CIT 使用比例分别为 34.4%和 37.3%，而非西班牙裔黑人患者的CIT 使用比例分别为 34.4%和 37.3%。不同祖裔群体之间的 TMB 水平差异显著（<0.001）；非洲裔患者的中位 TMB 最高（8.75 个突变/兆碱基；四分位间距，4.35-14.79）。在接受 CIT 的患者中，与低 TMB 相比，高 TMB 与整体生存率的提高相关（20.89 11.83 个月；危险比，0.60；95%CI，0.51 至 0.70），跨越基因组祖裔群体。
这些结果表明，公平获得下一代测序可能会改善在种族和祖裔多样化人群中 NSCLC 治疗结果的差异。
