Translating Molecular and Clinical Data to Biomarker-Informed Screening Pathway

项目摘要 肺癌仍然是全球公共卫生的优先事项。而低剂量计算机断层扫描（LDCT） 筛查显示肺癌死亡率降低20- 30%，但仍有未解决的问题。 挑战性问题，如优化LDCT筛查间隔以及如何最好地增加LDCT 筛查摄取率和依从性。此外，以前已经表明，肺癌的风险是 当吸烟暴露水平相同时，非裔美国人的吸烟率高于白人， 非裔美国人接受LDCT筛查的比例是最低的。而且 肺癌在从不吸烟者中的比例在世界各地继续上升，特别是在 在亚洲，超过50%的肺癌是在从不吸烟的人中诊断出来的。这些都没有出现 根据最近扩大的美国应急服务特别工作组标准解决问题。 该项目的总体目标是建立一个生物标志物知情的LDCT筛查途径， 最大限度地提高筛查效率和效益-危害比，同时考虑种族差异。我们的研究 正如我们已经建立的那样，团队处于进行这项急需的工作的独特位置 作为主要CT的主要研究者所需的数据元素的广泛资源 在美国、加拿大、欧洲和亚洲沿着与国际肺癌联盟合作开展筛查项目。 具体而言，我们将（i）建立生物标志物知情的LDCT筛查途径， 使用来自北美3个正在进行的LDCT筛查项目的数据和样本， 共有3500名参与者，对非裔美国人进行了过度抽样;（ii）确定循环 预测亚洲人肺癌风险和鉴别结节恶性肿瘤的生物标志物 吸烟者，使用台湾肺癌筛查从不吸烟者试验的数据和样本 （TALENT）与12，011例高风险亚洲从不吸烟者和311例LDCT检测到的肺癌病例 （iii）评估生物标志物对肺癌死亡率的预后价值， 多组学方法使用来自美国，加拿大， 欧洲和亚洲共有1267例肺癌病例。 该项目的结果将改变被认为是最佳CT筛查的范式 途径，解决代表性不足的人群的需求和潜在的过度诊断， 调查死亡率。它将为实施个人风险提供必要的信息- 基于特征的筛查策略，将提高效率，改善患者管理， 不同种族人群的肺癌死亡率。

Project Summary Lung cancer remains to be a global public health priority. While low-dose computed tomography (LDCT) screening was shown to reduce lung cancer mortality by 20-30%, there remain to be unresolved challenges issues such as optimizing intervals for LDCT screening and how best to increase LDCT screening uptake and adherence. In addition, it has been shown previously that lung cancer risks for African Americans are higher than for Whites when having the same level of smoking exposure, while uptake of LDCT screening among African Americans has been one of the lowest. Moreover, the proportion of lung cancer among never smokers continues to rise across the world, particularly among Asians where over 50% of lung cancers are diagnosed among never smokers. None of these emerging issues are addressed under the recently expanded US Preventative Service Task Force criteria. The overall objective of this project is to establish a biomarker-informed LDCT screening pathway to maximize screening efficiency and benefit-harm ratio while accounting for racial disparity. Our research team is in the unique position to conduct this much-needed work as we have already established extensive resources for the data elements needed being the lead investigators of the major CT screening programs in the US, Canada, Europe and Asia along with international lung cancer consortia. Specifically, we will (i) Establish a biomarker-informed LDCT screening pathway accounting for racial disparity using data and samples from 3 ongoing LDCT screening programs in North America, with a total of 3500 participants and oversampling African Americans; (ii) Identify circulating biomarkers that predict lung cancer risk and differentiate nodule malignancy in Asian never smokers, using data and samples from the Taiwan Lung Cancer Screening for Never Smoker Trial (TALENT) with 12,011 high-risk Asian never smokers and 311 lung cancer cases detected by LDCT screening; (iii) Assess the prognostic values of biomarkers for lung cancer mortality based on multi-omics approaches using data and samples from 6 LDCT screening studies from US, Canada, Europe and Asia with a total of 1267 lung cancer cases. The results from this Project will shift the paradigm of what is considered an optimal CT screening pathway and address the need of under-represented populations and potential over-diagnosis by investigating mortality. It will provide necessary information toward the implementation of individual risk- profile based screening strategies that will increase efficiency, improve patient management, and reduce lung cancer mortality in an ethnically diverse population.