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

项目总结/摘要 拟议的研究将描述胃肠道疾病的患病率和管理策略， 化生（GIM），一种消化道病变，影响美国约1210万成年人 并且是胃腺癌或胃癌（GC）的前体。虽然对GIM的大规模监视 不太可能在GC低患病率地区（如美国）有效，我们假设风险- 分层进行有针对性的筛查和监测将具有成本效益，并可改善结果。 广泛的GIM已被胃肠学会指南确定为进展的主要风险因素 但目前缺乏证据来了解GIM的总体患病率， 亚型（有限和广泛）在美国人口，或应如何管理。此外，最近 美国胃肠病协会提出的指南建议， 在少数种族/民族、外国出生的个体或具有幽门螺杆菌（H. 幽门螺杆菌）感染;然而，关于启动此类干预措施的阈值和 他们应该继续缺乏。K08申请中提出的研究将实现三个目标： 相关的具体目标。在目标1中，我们将利用退伍军人事务部医疗保健系统的数据， 描述GIM亚型的患病率和GIM进展为异型增生的风险因素，或 在美国背景下的恶性肿瘤这些数据将为Aim 2提供一个平台，我们将在其中建立一个模拟 从胃癌前病变进展到GC的自然史模型，以评估哪个个体- 水平的危险因素谱可能从GIM的筛查和监测中获益最多。该模型将使用64 不同的表型特征，按性别（男性/女性），种族/民族（非西班牙裔白色，西班牙裔， 黑人和亚洲人），GIM的程度（有限与广泛），外国出生的身份（移民与美国出生），和H。 幽门螺杆菌感染状态（既往/当前感染vs.无感染）。将根据数量报告结局 癌症预防率、生存率和增量成本效益比（ICER）。一旦最佳配置文件， 在患者水平上确定筛查方案，在目标3中，我们将评估以下人群水平的影响： 在美国实施这样一个关于医疗保健结果和成本的战略。漫长的发展窗口 从GIM到恶性肿瘤以及GC的低发病率使随机对照试验具有足够的效力 难仿真建模允许整合可用的知识来测试多个监视 GIM方案涵盖广泛的风险因素组合，在临床上不可行 问题研究到奖励期结束时，拟议的研究将利用国家病理学数据， 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组 在美国.建议、指导和咨询委员会、职业发展计划和机构 支持将奠定一个独立的NIH资助的职业生涯的基础。

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.