Integrated Molecular, Cellular, and Imaging Characterization of Screen-Detected Lung Cancer

 描述（由申请人提供）：加州大学洛杉矶分校-波士顿大学分子表征实验室（UCLA- BU MCL）是一个多学科的转化研究项目，旨在增强我们对在筛查检测和非筛查检测临床环境中区分惰性肺癌和侵袭性肺癌的分子、细胞和成像特征的理解。国家肺筛查试验（NLST）提供了令人信服的证据，证明使用低剂量螺旋计算机断层扫描（LDCT）进行肺癌筛查可降低肺癌死亡率。然而，筛查的好处必须与其潜在的危害相协调，包括高假阳性率和过度诊断的可能性。我们的广泛目标是通过询问与临床结果相关的分子，微环境和成像特征来区分惰性和侵袭性病变。这种全球性的方法使这些研究的各个方面都与我们对早期肺癌分子发病机制的理解有关。这些结果将转化为筛查检测肺癌的临床管理。了解导致异质性临床结果的肿瘤惰性或侵略性的潜在因素将有助于肺癌筛查背景下的临床决策，提高筛查有效性并最终推动护理途径。我们假设，通过分析筛查发现的病变的分子（全外显子组和mRNA测序）、微环境（免疫和炎症介质）和成像特征（语义和定量特征），将揭示筛查发现的肺癌异质性的潜在途径。具体目标是：目标1：识别分子、细胞和成像特征，以区分筛查发现的肺癌和非筛查发现的肺癌。目标二：识别分子、细胞和成像特征，以区分筛查检测的肺癌与NLST的惰性与侵袭性临床病程。目标3：确认和完善分子、细胞和成像特征，以区分前瞻性收集的筛查队列中筛查检测到的惰性与侵袭性临床病程的肺癌。病例将来自NLST生物储存库、DECAMP队列和加州大学（UC）全州范围内的一项倡议，该倡议涉及五个UC学术医疗中心，这些中心正在建立一个共同的筛查政策和平台，涉及临床、成像和组织标本的收集和存档。

 DESCRIPTION (provided by applicant): The University of California at Los Angeles - Boston University Molecular Characterization Laboratory (UCLA- BU MCL) is a multidisciplinary, translational research program designed to enhance our understanding of the molecular, cellular and imaging features distinguishing indolent from aggressive lung cancers in screen- detected and non-screen-detected clinical settings. The National Lung Screening Trial (NLST) has provided compelling evidence of the efficacy of lung cancer screening using low-dose helical computed tomography (LDCT) to reduce lung cancer mortality. The benefits of screening, however, must be reconciled with its potential harms, including high false positive rates and the potential for overdiagnosis. Our broad goal is to distinguish indolent from aggressive lesions by interrogating the molecular, microenvironment and imaging features that are associated with clinical outcomes. This global approach brings all aspects of these investigations to bear on our understanding of the molecular pathogenesis of early stage lung cancer. These results will be translated to the clinical management of screen-detected lung cancer. Understanding the factors underlying tumor indolence or aggression that result in heterogeneous clinical outcomes will facilitate clinical decision making in the context of lung cancer screening, increase screening effectiveness and ultimately drive care pathways. We hypothesize that the pathways underlying heterogeneity in screen-detected lung cancers will be revealed by analysis of molecular (whole exome and mRNA sequencing), microenvironment (immune and inflammatory mediators) and imaging characteristics (semantic and quantitative features) of screen- detected lesions. The specific aims are: Aim 1: Identify molecular, cellular and imaging profiles that distinguish screen-detected from non-screen- detected lung cancers. Aim 2: Identify molecular, cellular and imaging profiles that distinguish screen-detected lung cancers with indolent versus aggressive clinical courses from the NLST. Aim 3: Confirm and refine molecular, cellular and imaging profiles that distinguish screen-detected lung cancers with indolent versus aggressive clinical courses from a prospectively collected screening cohort. Cases will derive from the NLST biorepository, DECAMP cohorts and a University of California (UC) state-wide initiative involving the five UC academic medical centers that are establishing a common screening policy and platform that involves the collection and archiving of clinical, imaging, and tissue specimens.