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：
9980310
负责人：
Amit Singal
金额：
$ 69.3万
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/9980310
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 Prospective cohort Protocols documentation Public Health Quality-Adjusted Life Years Risk Risk Factors Risk stratification 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 outcome forecast patient population performance tests personalized screening precision medicine prospective 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

项目概要/摘要鉴于两者之间的关联，美国肝细胞癌 (HCC) 相关死亡率正在迅速上升。早期检测并提高生存率，使用超声筛查+/-血清生物标志物、甲胎蛋白 (AFP)，建议高危人群使用，包括所有肝硬化患者，但大多数 HCC 患者。由于该策略的局限性，特别是超声和 AFP 的策略，诊断已处于晚期。在所有肝硬化患者中进行评估是不充分的，因为它忽略了：1）患者之间风险的异质性；2）穷人；筛查测试的准确性；3) 患者之间筛查测试表现的可靠性较差。目前“一刀切”的 HCC 筛查方法导致对低风险肝硬化患者的过度筛查，对高危患者的筛查不足，削弱了 HCC 筛查的整体价值。我们提案的目标是开发和评估早期 HCC 患者的精准筛查策略我们将针对肝硬化患者，将最佳筛查测试与个人风险和筛查测试表现相匹配。利用总共超过 6000 名患者的 5 个患者群体（4 个前瞻性队列和一个病例对照数据集）肝硬化患者评估和比较基于生物标志物和成像的 HCC 风险分层模型具体来说，我们建议：目标 1：验证并比较两种风险分层模型的性能，以对肝硬化患者进行分层发生 HCC 的低、中、高风险目标 2：评估简化 MRI 方案 +/- 血清生物标志物（包括 AFP、AFP- L3 和 DCP）与超声 +/- 血清生物标志物对肝硬化患者早期 HCC 检测的比较目标 3：使用微观模拟模型比较定制筛选策略的成本效益基于个体 HCC 风险和预期筛查测试表现，采用当前标准策略所有肝硬化患者的超声和 AFP 我们的提案利用 5 个不同的患者群体（超过 6000 名肝硬化患者）来比较生物标志物和我们使用这些数据来比较基于成像的 HCC 风险分层和早期检测模型。针对所有患者当前超声和 AFP 策略的定制筛查策略的有效性使用微观模拟模型根据个体风险和筛查测试定制 HCC 筛查工作。性能超越了当前的“一刀切”策略，并使 HCC 筛查与原则保持一致我们提出的 HCC 筛查策略将最大限度地提高筛查效益并最大限度地减少筛查效益。筛查对每位患者造成伤害，从而优化美国的整体 HCC 筛查价值。 2