Precision Risk Stratification and Screening for HCC among Patients with Cirrhosis in the United States

美国肝硬化患者的 HCC 精准风险分层和筛查

基本信息

批准号：
10225536
负责人：
Amit Singal
金额：
$ 70.17万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-14 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10225536
关键词：
Abdomen Biological Markers Blinded Blood Body mass index Cause of Death Center for Translational Science Activities Characteristics Cirrhosis Cohort Studies Complement Data Data Set Detection Diagnosis Early Detection Research Network Early Diagnosis Etiology Evaluation Funding Goals Heterogeneity Image Individual Liver diseases Magnetic Resonance Imaging Michigan Modeling Molecular Profiling Patients Performance Primary carcinoma of the liver cells Professional Organizations Prognosis Prospective cohort Protocols documentation Public Health Quality-Adjusted Life Years Risk Risk Factors Role Serum Severities Severity of illness Subgroup Testing Texas Ultrasonography United States Universities alpha-Fetoproteins base biomarker panel biomarker performance case control clinical risk cohort comparative cost effectiveness compare effectiveness contrast enhanced cost effective cost effectiveness curative treatments design early detection biomarkers effectiveness testing high risk imaging biomarker improved individual patient models and simulation mortality novel patient population performance tests personalized screening precision medicine prospective risk stratification sample collection screening sex standard of care tumor

项目摘要

PROJECT SUMMARY / ABSTRACT Hepatocellular carcinoma (HCC)-related mortality in the U.S. is rapidly rising. Given the association between early detection and improved survival, screening using ultrasound +/- a serum biomarker, alpha fetoprotein (AFP), is recommended in at-risk individuals, including all patients with cirrhosis. However, most HCC patients are diagnosed at a late stage due to limitations in this strategy. Specifically, the strategy of ultrasound and AFP in all cirrhosis patients is inadequate because it ignores: 1) heterogeneity in risk between patients; 2) the poor accuracy of screening tests; and 3) the poor reliability of screening test performance between patients. The current “one-size-fits-all” approach to HCC screening leads to over-screening of low-risk cirrhosis patients and under-screening of high-risk patients, diluting the overall value of HCC screening. Our proposal's goal is to develop and evaluate a precision screening strategy for early stage HCC in patients with cirrhosis that matches the best screening tests to individual risk and screening test performance. We will leverage five patient populations (4 prospective cohorts and one case-control dataset) with a total of >6000 cirrhosis patients to evaluate and compare biomarker- and imaging-based models for HCC risk stratification and early detection. Specifically, we propose to: Aim 1: Validate and compare the performance of two risk stratification models to stratify cirrhosis patients with low-, intermediate- and high-risk of developing HCC Aim 2: Evaluate the performance of an abbreviated MRI protocol +/- serum biomarkers (including AFP, AFP- L3, and DCP) vs. ultrasound +/- serum biomarkers for early HCC detection in patients with cirrhosis Aim 3: Compare the cost effectiveness, using micro-simulation modeling, of a tailored screening strategy based on individual HCC risk and expected screening test performance to the current standard strategy of ultrasound and AFP in all patients with cirrhosis Our proposal leverages 5 distinct patient populations with >6000 cirrhosis patients, to compare biomarker- and imaging-based models for HCC risk stratification and early detection. We use these data to compare the effectiveness of a tailored screening strategy to the current strategy of ultrasound and AFP for all patients using micro-simulation modeling. Tailoring HCC screening efforts to individual risk and screening test performance moves beyond the current “one-size-fits-all” strategy and aligns HCC screening with the principles of precision medicine. Our proposed HCC screening strategy would maximize screening benefits and minimize screening harms for each patient, thereby optimizing overall HCC screening value in the United States. 2

项目摘要 /摘要在美国，肝细胞癌（HCC）相关的死亡率正在迅速上升。考虑到早期检测和提高的生存率，使用超声+/-血清生物标志物α，α胎蛋白进行筛查（法新社）建议在包括所有肝硬化患者在内的高危个体中使用。但是，大多数HCC患者由于此策略的局限性，在后期被诊断出来。具体而言，超声和法新社的策略在所有肝硬化患者中，患者忽略了：1）患者之间的风险异质； 2）穷人筛选测试的准确性； 3）患者筛查测试表现的可靠性差。当前的HCC筛查方法当前的“千篇一律”方法导致低风险肝硬化患者和高危患者的筛查不足，从而稀释了HCC筛查的整体价值。我们的提议的目标是制定和评估患者早期HCC的精确筛查策略肝硬化与最佳筛查测试与个体风险和筛查测试表现相匹配。我们将利用五个患者人群（4个前瞻性队列和一个病例控制数据集），总计> 6000 肝硬化患者评估和比较基于生物标志物和成像模型的HCC风险分层和早期检测。具体来说，我们建议： AIM 1：验证和比较两个风险分层模型的性能，以将肝硬化患者分层发育中的低风险和高风险的HCC AIM 2：评估缩写MRI方案+/-血清生物标志物的性能（包括AFP，AFP- L3和DCP）与超声+/-肝硬化患者早期HCC检测的超声+/-血清生物标志物目标3：使用微模型建模比较量身定制筛选策略的成本效益基于单独的HCC风险和预期筛选测试性能所有肝硬化患者的超声和法新社我们的提议利用5例患者的5例患者，以比较生物标志物和基于成像的HCC风险分层和早期检测模型。我们使用这些数据比较针对所有患者的当前超声和法新社策略的量身定制筛选策略的有效性使用微型模拟建模。调整HCC筛查工作以进行个人风险和筛查测试绩效超出了当前的“千篇一律”策略，并使HCC筛查与原则保持一致精密医学。我们提出的HCC筛查策略将最大化筛查优势并最大程度地减少对每个患者的筛查损害，从而优化了美国的总体HCC筛选价值。 2