Evaluation of genetic, clinical, and environmental risk factors to establish effective screening strategies for second primary lung cancer

肺癌(LC)是美国癌症死亡的主要原因。 体层摄影术(CT)筛查能够及早发现肺癌，预计将增加肺癌的数量 长期的LC幸存者。截至2012年，估计LC幸存者人数约为412,230人， 预计到2022年将超过50万。最近的研究表明，LC幸存者有很高的风险 发展为第二原发癌(SPLC)，其发病率约为中国的4-6倍 最初的原发肺癌(IPLC)在普通人群中。虽然国家肺部筛查指南一直在 由美国预防服务工作组(USPSTF)为IPLC建立的，没有这样的共识指导方针 存在于暴露于SPLC高危人群中的LC幸存者。此外，影响经济增长的因素 SPLC的开发还没有建立起来。我们的长期目标是降低LC的总体死亡率 通过关注SPLC在美国人口中的应用。此应用程序的总体目标是识别 SPLC的遗传、临床和环境决定因素，以评估个人患SPLC的风险， 并评估SPLC的有效肺部筛查策略，以帮助了解共识的发展 LC幸存者筛查指南。我们的目标是：(目标1)确定遗传、环境、临床、 以及人口统计学风险因素，并建立了人口统计学风险预测模型。我们将使用队列 肺癌跨学科研究(TRICL)与国际肺癌 (ILCCO)评估SPLC的危险因素；(AIM 2)评估最佳CT筛查策略 通过估计不同选择下CT筛查的人群水平危害和好处来评估SPLC 标准。我们将开发一个SPLC的随机模拟模型，该模型集成了发病率、进行性和 SPLC的存活率，以量化在不同风险下筛查SPLC的人群水平的危害和好处 基于选择标准；(目标3)估算CT的生命周期成本并评估其成本效益 在美国普通人群中筛查SPLC的策略。我们研究的贡献将是 意义重大，因为它将通过识别各种风险来更好地了解SPLC的病因 使用基于人口的综合数据对SPLC的影响因素。第二，我们的研究工作完成后， 为评估个人罹患SPLC的风险提供有价值的决策工具，这有助于确定 进行筛查的高危个体。最后，通过评估肺癌的潜在危害和好处 在各种标准下，我们的研究将提供一套最佳的CT筛查策略， 其结果将减少临床医生对如何最好地指导LC幸存者进行CT筛查的不确定性。

Lung cancer (LC) is a leading cause of cancer deaths in the U.S. The widespread adoption of computed tomography (CT) screening enables the early detection of lung cancer and is expected to increase the number of long-term LC survivors. The estimated number of LC survivors is approximately 412,230 as of 2012 and is projected to be over a half million in 2022. Recent studies show that LC survivors have a high risk of developing second primary lung cancer (SPLC), the incidence of which is around 4-6 times higher than that of initial primary lung cancer (IPLC) in the general population. While national lung screening guidelines have been established for IPLC by the U.S. Preventive Services Task Force (USPSTF), no such consensus guidelines exist for LC survivors who are exposed to a high risk of SPLC. Furthermore, the factors that contribute to the development of SPLC have not yet been established. Our long-term goal is to reduce the overall LC mortality in the U.S. population by focusing on SPLC. The overall objectives of this application are to identify the genetic, clinical, and environmental determinants for SPLC, to assess an individual’s risk of developing SPLC, and to evaluate efficient lung screening strategies for SPLC to help inform the development of consensus screening guidelines for LC survivors. Our aims are: (AIM 1) To identify the genetic, environmental, clinical, and demographic risk factors for SPLC and to develop a risk prediction model for SPLC. We will use cohort data from the Transdisciplinary Research in Cancer of the Lung (TRICL) and the International Lung Cancer Consortium (ILCCO) to evaluate risk factors for SPLC; (AIM 2) To evaluate optimal CT screening strategies for SPLC by estimating the population-level harms and benefits of CT screening under various selection criteria. We will develop a stochastic simulation model for SPLC that integrates the incidence, progression, and survival of SPLC to quantify the population-level harms and benefits of screening for SPLC under various risk- based selection criteria; (AIM 3) To estimate the lifetime costs and to assess the cost-effectiveness of CT screening strategies for SPLC in the general U.S. population. The contribution of our research will be significant because it will provide a better understanding of the etiology of SPLC by identifying various risk factors for SPLC using comprehensive population-based data. Second, the completion of our research will provide a valuable decision tool for evaluating an individual’s risk of developing SPLC, which can help identify high-risk individuals for screening. Finally, by evaluating the potential harms and benefits of lung cancer screening for SPLC under various criteria, our research will provide a set of optimal CT screening strategies, the results of which will reduce clinicians’ uncertainty on how to best guide LC survivors for CT screening.