Translating Molecular and Clinical Data to Biomarker-Informed Screening Pathway

将分子和临床数据转化为生物标志物知情的筛选途径

• 批准号: 10716719
• 负责人: Rayjean J. Hung
• 金额: $ 66.29万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10716719
• 关键词: Academic Medical Centers; Accounting; Address; Adherence; African American population; Asia; Asian; Asian population; Benign; Biological Assay; Biological Markers; Calibration; Canada; Cancer Etiology; Cessation of life; Classification; Clinical Data; Collaborations; Communities; Data; Data Element; Diagnosis; Diagnostic; Early Diagnosis; Epidemiology; Europe; Focus Groups; Frequencies; Genetic; Genomics; Goals; Image; Individual; International; Lead; Lung; Lung nodule; Machine Learning; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of lung; Measures; Methods; Minority Groups; Modeling; Molecular; Nodule; North America; Ontario; Participant; Pathway interactions; Patients; Population Heterogeneity; Positioning Attribute; Probability; Proteins; Race; Research; Research Personnel; Resources; Risk; Risk Management; Risk Reduction Behavior; Role; Sampling; Site; Smoking Status; Spirometry; Taiwan; Translating; Translations; Underrepresented Populations; United Kingdom; United States Preventative Services Task Force; Universities; Validation; Visit; Washington; Work; biomarker panel; biomarker validation; cancer diagnosis; cancer risk; case control; circulating biomarkers; cohort; community engagement; computed tomography screening; data resource; design; epidemiologic data; ethnic diversity; feature selection; high risk; improved; low dose computed tomography; lung cancer screening; model building; mortality; multiple omics; never smoker; predictive marker; prognostic value; programs; prospective; protein biomarkers; public health priorities; racial disparity; radiomics; screening; screening program; sex; smoking exposure; uptake

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.

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) 筛查显示可以将肺癌死亡率降低20-30%，这一问题仍有待解决 挑战问题，如优化LDCT筛查间隔以及如何最好地提高LDCT 筛选摄取和依从性。此外，以前已经表明，肺癌的风险 在吸烟水平相同的情况下，非裔美国人的吸烟水平高于白人，而 非裔美国人接受LDCT筛查的比例一直是最低的之一。此外， 世界各地从不吸烟的人患肺癌的比例继续上升，特别是在 在亚洲，超过50%的肺癌是在从不吸烟的人中被诊断出来的。所有这些都不会出现 这些问题是在最近扩大的美国预防性服务工作组标准下解决的。 该项目的总体目标是建立一个生物标志物信息的LDCT筛查途径，以 最大限度地提高筛查效率和利害比，同时考虑种族差异。我们的研究 正如我们已经建立的那样，团队处于独特的地位来进行这项亟需的工作 作为主要CT的主要调查员所需的数据元素的广泛资源 美国、加拿大、欧洲和亚洲的筛查项目以及国际肺癌联盟。 具体地说，我们将(I)建立一个生物标志物信息的LDCT筛查途径，以说明 使用北美正在进行的3个LDCT筛查项目的数据和样本进行种族差异， 共有3500名参与者和过多抽样的非裔美国人；(2)查明正在传播的 预测亚洲人肺癌风险和鉴别结节恶性的生物标志物 吸烟者，使用台湾肺癌筛查从不吸烟试验的数据和样本 (人才)LDCT检测出12011名亚洲从不吸烟的高危人群和311例肺癌病例 筛查；(Iii)评估生物标记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 途径和解决代表性不足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- 基于配置文件的筛查策略，将提高效率、改善患者管理并减少 不同种族人群中的肺癌死亡率。