Clinical Risk Assessment and Prediction

食管腺癌（EA）的死亡率在过去四十年中急剧上升。努力 预防和控制反映了巴雷特食管（BE）作为一种流行的范式 反流的并发症，并大大倾向于EA;因此，医疗保健的重点是确定 从反流患者中分离BE患者，将其纳入长期监测，并积极 在他们患上侵袭性癌症之前进行治疗。然而，EA死亡率的持续增加， 95%的BE患者永远不会发展为癌症，这一事实强调了这种方法的无效性。 approach.项目2直接建立在P01团队的最新进展之上，以解决 更有效的预防和控制措施。在过去的5年里，我们发表或提交了41份 研究手稿解决项目2的问题和目标。在更新期间，我们将利用富人 和全面的数据资源，包括主机和环境风险因素，医疗 记录、血清测定、高密度基因分型和食管活检）， 600名参与者的队列，77例EA结局。在aim 1中，我们将开发定制的风险和预测模型 EA的绝对风险，这将有助于临床决策。在目标2中，我们将评估总结 体细胞基因组改变（SGA）的全基因组测量，关于其增加的预测价值。在 作为一个探索性的目的，我们将研究一种有争议的新治疗方法，射频消融术， 高危患者的基因组异常在目标3中，我们将把目标1的成果与SGA合并 平台，并使用计算机模拟来考虑依赖于时间的疾病动态， 制定和评估优化的监测和预防方案。结果将与 利用BEACON联盟的资源参与早期阶段风险评估的调查人员， 并随着时间的推移通过与其他队列的交叉验证得到改善。项目2旨在 巩固和扩展整个POI期间的关键发现，以推进临床实践， 加强EA预防和控制。 相关性（参见说明）： 食管腺癌的发病率上升速度比任何其他癌症都快。我们建议解决 通过开发和广泛提供一套预防和控制这种癌症的重要障碍 用于Barrett食管风险预测和监测的临床工具将得到验证并应用于 公共卫生、临床和研究环境。

Mortality from esophageal adenocarcinoma (EA) has risen dramatically over four decades. Efforts towards prevention and control have reflected the prevailing paradigm that Barrett's esophagus (BE) arises as a complication of reflux and greatly predisposes to EA; consequently medical care has focused on identifying persons with BE from among those with reflux, enrolling them in long-term surveillance, and aggressively treating them before they develop invasive cancer. However, the continued increase in EA mortality, coupled with the fact that 95% of BE patients will never progress to cancer, underscores the ineffectiveness of this approach. Project 2 builds directly on recent advances made by the P01 team to address critical barriers to a more effective program of prevention and control. In the past 5 years, we have published or submitted 41 research manuscripts addressing Project 2 issues and aims. During the renewal period we will utilize the rich and comprehensive data resources ofthe POl (including host and environmental risk factors, medical records, serum assays, high-density genotyping, and esophageal biopsies) collected prospectively on a BE cohort of 600 participants with 77 EA outcomes. In aim 1 we will develop risk and prediction models tailored to the absolute risk of EA that will be useful for clinical decision-making. In aim 2 we will evaluate summary genome-wide measures of somatic genomic alterations (SGA) with regard to their added predictive value. In an exploratory aim we will examine the effects of a controversial new treatment, radio frequency ablation, on genomic abnormalities in high-risk patients. In aim 3 we will consolidate the results from aim 1 with the SGA platform from aim 2, and use computer simulation to take into account time-dependent disease dynamics to develop and evaluate an optimized surveillance and prevention protocol. Results will be shared with investigators involved with risk assessment of eariier stages using resources of the BEACON consortium, and improved over time by cross-validation with other cohorts as they develop. Project 2 seeks to consolidate and extend key discoveries over the entire period of the POl to advance clinical practice and improve EA prevention and control. RELEVANCE (See instructions): The incidence of esophageal adenocarcinoma is rising faster than any other cancer. We propose to address important barriers to prevention and control of this cancer by developing and making broadly available a set of clinical tools for risk prediction and surveillance of Barrett's esophagus to be validated and applied in public health, clinical and research settings.