Accounting for EGFR Mutations in Epidemiologic Analyses of Non-Small Cell Lung Cancers: Examples Based on the International Lung Cancer Consortium Data.
Accounting for EGFR Mutations in Epidemiologic Analyses of Non-Small Cell Lung Cancers: Examples Based on the International Lung Cancer Consortium Data.
复制标题
DOI：
10.1158/1055-9965.epi-21-0747
复制
发表时间：
2022-03-01
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
体细胞EGFR突变定义了对NSCLC风险和结局具有临床影响的非小细胞肺癌（NSCLC）亚组。然而，EGFR突变状态在流行病学数据集中经常缺失。我们开发并测试了实用的方法来解释EGFR突变状态的变量通常包括在流行病学数据集的基础上，并评估这些方法的临床效用。通过对国际肺癌联盟（ILCCO）流行病学数据集的分析，我们开发了一个EGFR状态的回归模型;然后，我们应用了一种使用最佳临界点的临床限制方法，以及第二种流行病学，多重插补方法对ILCCO生存分析进行了解释和不解释EGFR状态。在35，356例ILCCO非小细胞肺癌患者中，有4231例患者的EGFR突变状态可用。回归已知EGFR突变状态的临床和人口统计学变量的模型在训练数据集中达到0.75（95%CI：0.74-0.77）的一致性指数，在测试数据集中达到0.77（95%CI：0.74-0.79）。在概率分数=0.335的最佳临界点，确定EGFR野生型状态的灵敏度=69%，特异性=72.5%。在BMI对NSCLC患者总生存期的个体作用的基于限制和基于插补的回归分析中，在所有血统患者的总体和EGFR突变阴性队列分析之间观察到相似的结果。然而，我们的方法发现了一些差异：EGFR突变的亚洲患者并没有像EGFR野生型亚洲患者那样因肥胖而获得生存益处。我们介绍了一种实用的方法来评估EGFR状态对NSCLC流行病学分析的潜在影响。所提出的方法是可推广的EGFR状态数据丢失的常见情况。
Somatic EGFR mutations define a subset of non-small cell lung cancers (NSCLC) that have clinical impact on NSCLC risk and outcome. However, EGFR-mutation-status is often missing in epidemiological datasets. We developed and tested pragmatic approaches to account for EGFR-mutation-status based on variables commonly included in epidemiological datasets and evaluated the clinical utility of these approaches. Through analysis of the International Lung Cancer Consortium (ILCCO) epidemiological datasets, we developed a regression model for EGFR-status; we then applied a clinical-restriction approach using the optimal cutpoint, and a second epidemiological, multiple imputation approach to ILCCO survival analyses that did and did not account for EGFR-status. Of 35,356 ILCCO patients with NSCLC, EGFR-mutation-status was available in 4231 patients. A model regressing known EGFR-mutation-status on clinical and demographic variables achieved a concordance-index of 0.75 (95%CI: 0.74–0.77) in the training and 0.77 (95%CI: 0.74–0.79) in the testing dataset. At an optimal cut-point of probability-score=0.335, sensitivity=69% and specificity=72.5% for determining EGFR-wildtype status. In both restriction-based and imputation-based regression analyses of the individual roles of BMI on overall survival of NSCLC patients, similar results were observed between overall and EGFR-mutation-negative cohort analyses of patients of all ancestries. However, our approach identified some differences: EGFR-mutated Asian patients did not incur a survival benefit from being obese, as observed in EGFR-wildtype Asian patients. We introduce a pragmatic method to evaluate the potential impact of EGFR-status on epidemiological analyses of NSCLC. The proposed method is generalizable in the common occurrence in which EGFR-status data are missing.
影响因子：
2.9
作者：
Chang H;Liu YB;Yi W;Lu JB;Zhang JX
通讯作者：
Zhang JX