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

胃癌前驱病变监测的有针对性的方法

基本信息

批准号：
10392490
负责人：
Monika Laszkowska
金额：
$ 16.76万
依托单位：
SLOAN-KETTERING INST CAN RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-01 至 2026-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10392490
关键词：
Accounting Adult Advisory Committees Affect Age American Asian Award Bass Cancer Model Clinical Research Collection Colorectal Cancer Computer Simulation Country Coupled Data Databases Development Plans Diffuse gastric cancer Dysplasia Early Intervention Epithelial Ethnic Origin Europe Family Female Funding Gastric Adenocarcinoma Gastrointestinal tract structure Gender Guidelines Health Healthcare Systems Helicobacter Infections Helicobacter pylori High Prevalence Hispanic Hospitals Immigrant Incidence Individual Infection Inherited Intervention Investigation Japan Knowledge Lesion Low Prevalence Malignant Neoplasms Mass Screening Mentorship Modeling Natural History Not Hispanic or Latino Operative Surgical Procedures Outcome Pathology Patients Phenotype Policies Population Precancerous Conditions Prevalence Public Health Publishing Race Randomized Controlled Trials Recording of previous events Regimen Reporting Research Research Personnel Risk Risk Factors SEER Program Screening for Gastric Cancer Smoking History Societies Specimen Stomach Subgroup System Testing United States United States Department of Veterans Affairs United States National Institutes of Health Veterans Health Administration Work base biomarker signature cancer subtypes care costs care outcomes career career development cohort cost cost effective cost-effectiveness ratio curative treatments ethnic difference ethnic minority gastric intestinal metaplasia gastrointestinal high risk i(19)improved improved outcome incremental cost-effectiveness intervention program male malignant stomach neoplasm models and simulation mortality premalignant prevent preventive intervention profiles in patients prophylactic prospective racial and ethnic racial difference response risk stratification screening screening program surveillance data

项目摘要

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.

项目概要/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 (US) 约 1210 万成年人并且是胃腺癌或胃癌 (GC) 的前兆。虽然对 GIM 的大规模监视是在美国等胃癌发病率较低的地区不太可能有效，我们假设风险有针对性的筛查和监测的分层将具有成本效益，并且可以改善结果。胃肠道学会指南已将广泛的 GIM 确定为进展的主要危险因素 GC，但目前缺乏证据来了解 GIM 的总体患病率以及美国人口中的亚型（有限的和广泛的），或者应该如何管理。此外，最近美国胃肠病学协会提出的指南建议应监测 GIM 考虑到少数种族/族裔、外国出生的个人或有幽门螺杆菌病史的人（H. 幽门螺杆菌）感染；然而，关于启动此类干预措施的门槛和间隔时间的证据他们应该继续缺乏。本 K08 申请中提出的研究将完成三个任务相互关联的具体目标。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来描述 GIM 亚型的患病率以及 GIM 进展为不典型增生或不典型增生的危险因素美国背景下的恶性肿瘤。这些数据将为 Aim 2 提供一个平台，我们将在其中构建一个模拟从癌前胃病变进展到GC的自然史模型，以评估哪个个体- 水平风险因素概况可以从 GIM 筛查和监测中获益最多。该模型将利用 64 不同的表型特征，按性别（男性/女性）、种族/民族（非西班牙裔白人、西班牙裔、黑人和亚洲人）、GIM 范围（有限与广泛）、外国出生身份（移民与美国出生）和 H. 幽门螺杆菌感染状态（先前/当前感染与无感染）。结果将根据数量报告预防癌症的数量、生存率和增量成本效益比 (ICER)。一旦获得最佳配置文件并筛查方案是在患者层面确定的，在目标 3 中，我们将评估人群层面的影响在美国实施这样的医疗保健结果和成本战略。漫长的进步窗口从 GIM 到恶性肿瘤以及 GC 的低发生率使得随机对照试验具有足够的说服力难的。仿真建模允许集成可用知识来测试多个监视涵盖广泛危险因素组合的 GIM 治疗方案，这在临床上是不可行的研究。到奖励期结束时，拟议的研究将利用国家病理学数据以及模拟建模以确定可能从监测中受益最多的特定高危患者亚组在美国。提案、指导和咨询委员会、职业发展计划和制度支持将为 NIH 资助的独立职业奠定基础。