A Targeted Approach to the Surveillance of Precursor Lesions for Gastric Cancer

项目摘要/摘要 拟议的研究将描述胃肠道疾病的流行和管理策略。 化生(GIM)，一种消化道病变，影响美国约1,210万成年人 是胃腺癌或胃癌(GC)的先兆。而对GIM的大规模监控是 不太可能在美国等GC发病率较低的地区有效，我们假设风险- 有针对性的筛查和监测的分层将是具有成本效益的，并可以改善结果。 胃肠道协会指南已将广泛性GIM确定为进展的主要危险因素 对GC来说，但目前缺乏证据来全面了解GIM的流行情况 美国人口中的亚型(有限和广泛)，或者应该如何管理。此外，最近 来自美国胃肠病协会的拟议指南建议，对GIM的监测应该 考虑在种族/少数民族、外国出生的个人或有幽门螺杆菌病史(H。 幽门螺杆菌)感染；然而，关于启动这种干预措施的阈值和间隔时间的证据 他们应该继续下去，但却缺乏。在本K08申请中提出的研究将完成三个 相互关联的具体目标。在目标1中，我们将利用整个退伍军人事务部医疗保健系统的数据来 描述牙周炎各亚型的患病率以及牙周炎进展为不典型增生的危险因素。 美国语境中的恶意性。这些数据将为AIM 2提供一个平台，我们将在其中建立一个模拟 从癌前病变到GC的自然发展史模型，以评估哪个个体- 水平危险因素谱可从GIM的筛查和监测中获益最多。该模式将利用 不同的表型特征，按性别(男性/女性)、种族/民族(非西班牙裔白人、西班牙裔、 黑人和亚洲人)、吉姆人的范围(有限的与广泛的)、外国出生的身份(移民与美国出生的人)以及H。 幽门螺杆菌感染状况(以前/现在感染与未感染)。结果将根据数字报告 癌症预防、存活率和增量成本-效果比(ICER)。一旦获得最佳配置文件， 筛查方案是在患者层面上确定的，在目标3中，我们将评估 在美国实施这样一项关于医疗保健结果和成本的战略。漫长的进步之窗 从牙周炎到恶性肿瘤和低发病率的GC使随机对照试验变得足够有力 很难。模拟建模允许集成可用的知识来测试多个监视 在广泛的风险因素组合中使用GIM方案，这在临床上是不可行的 学习。到获奖期结束时，拟议的研究将利用国家病理学数据与 模拟建模以确定可能从监测中获益最多的特定高危患者亚群 在美国。提议、指导和咨询委员会、职业发展计划和机构 支持将为NIH资助的独立职业生涯奠定基础。

Project Summary/Abstract The proposed research will characterize the prevalence and management strategies of gastric intestinal metaplasia (GIM), a lesion of the digestive tract that affects about 12.1 million adults in the United States (US) and is a precursor to gastric adenocarcinoma, or gastric cancer (GC). While mass surveillance of GIM is unlikely to be effective in regions of low-prevalence for GC such as the US, we hypothesize that risk- stratification for targeted screening and surveillance will be cost-effective and can improve outcomes. Extensive GIM has been identified by gastrointestinal society guidelines as a major risk factor for progression to GC, but there is currently a dearth of evidence in understanding the prevalence of GIM overall and by subtype (limited and extensive) in the US population, or how it should be managed. Furthermore, the recently proposed guidelines from the American Gastroenterological Association suggest surveillance of GIM should be considered in racial/ethnic minorities, foreign-born individuals, or those with a history of Helicobacter pylori (H. pylori) infection; however, evidence on the threshold to initiate such interventions and the intervals at which they should be continued is lacking. The research proposed in this K08 application will accomplish three interrelated Specific Aims. In Aim 1, we will utilize data from across the Veterans Affairs health care system to characterize the prevalence of subtypes of GIM and risk factors for progression of GIM to dysplasia or malignancy in the US context. These data will provide a platform for Aim 2, in which we will build a simulation model of the natural history of progression from precancerous gastric lesions to GC to assess which individual- level risk factor profiles could benefit most from screening and surveillance of GIM. The model will utilize 64 different phenotypic profiles, stratified by: gender (male/female), race/ethnicity (non-Hispanic white, Hispanic, black, and Asian), extent of GIM (limited vs. extensive), foreign-born status (immigrant vs. US-born), and H. pylori infection status (previous/current infection vs. no infection). Outcomes will be reported based on number of cancers prevented, survival, and incremental cost-effectiveness ratios (ICERs). Once an optimal profile and screening regimen is identified on the patient level, in Aim 3 we will assess the population-level impact of implementing such a strategy on health care outcomes and costs in the US. The long window of progression from GIM to malignancy and the low incidence of GC make sufficiently powered randomized controlled trials difficult. Simulation modeling allows for the integration of available knowledge to test multiple surveillance regimens of GIM across a broad range of risk factor combinations, which would not be feasible in clinical studies. By award period end, the proposed research will utilize national pathology data coupled with simulation modeling to identify a specific subgroup of high-risk patients that may benefit most from surveillance in the US. The proposal, mentorship and advisory committee, career development plans and institutional support will lay the basis for an independent NIH-funded career.