论文标题
基于H&E的计算生物标志物可实现肺腺癌的通用EGFR筛查
H&E-based Computational Biomarker Enables Universal EGFR Screening for Lung Adenocarcinoma
论文作者
论文摘要
肺癌是全球癌症死亡的主要原因,肺腺癌是肺癌最普遍的形式。 EGFR阳性肺腺癌已被证明对TKI治疗的反应率很高,这是肺癌分子测试的基本性质。尽管当前的指南认为必要测试,但很大一部分患者并未常规化,导致数百万的人未接受最佳治疗肺癌。测序是EGFR突变分子测试的黄金标准,但是结果可能需要数周的时间才能恢复,这在时间限制的情况下并不理想。能够快速,便宜地检测EGFR突变的同时保存组织进行测序的替代筛查工具的开发可以帮助减少受比较治疗的患者的数量。我们提出了一种多模式方法,该方法将病理图像和临床变量整合在一起,以预测EGFR突变状态,迄今为止,最大的临床队列中的AUC为84%。这样的计算模型可以以很少的额外成本进行大部分部署。它的临床应用可以减少中国接受亚最佳治疗的患者数量53.1%,在美国将高达96.6%的患者减少96.6%。
Lung cancer is the leading cause of cancer death worldwide, with lung adenocarcinoma being the most prevalent form of lung cancer. EGFR positive lung adenocarcinomas have been shown to have high response rates to TKI therapy, underlying the essential nature of molecular testing for lung cancers. Despite current guidelines consider testing necessary, a large portion of patients are not routinely profiled, resulting in millions of people not receiving the optimal treatment for their lung cancer. Sequencing is the gold standard for molecular testing of EGFR mutations, but it can take several weeks for results to come back, which is not ideal in a time constrained scenario. The development of alternative screening tools capable of detecting EGFR mutations quickly and cheaply while preserving tissue for sequencing could help reduce the amount of sub-optimally treated patients. We propose a multi-modal approach which integrates pathology images and clinical variables to predict EGFR mutational status achieving an AUC of 84% on the largest clinical cohort to date. Such a computational model could be deployed at large at little additional cost. Its clinical application could reduce the number of patients who receive sub-optimal treatments by 53.1% in China, and up to 96.6% in the US.