Risk Stratification for and Early Detection of Liver Cancer

肝癌的风险分层和早期发现

基本信息

批准号：
10473708
负责人：
FASIHA KANWAL
金额：
$ 64.75万
依托单位：
BAYLOR COLLEGE OF MEDICINE
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：
2018-09-13 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10473708
关键词：
African American population Age Alcohols Algorithms Area Behavioral Genetics Biological Assay Biological Markers Biological Specimen Banks Blinded Blood Center for Translational Science Activities Cirrhosis Clinical Clinical/Radiologic Cohort Studies Collaborations DNA Markers Data Detection Development Early Detection Research Network Early Diagnosis Ethnic Origin Ethnic group Etiology Evaluation Funding Future Genetic Genetic Markers Goals Hepatitis C virus Hispanic Americans Hispanic Populations Image Individual Infrastructure Laboratories Liver diseases Malignant neoplasm of liver Medical center Methods Mission Modernization Morbidity - disease rate Multicenter Studies Patients Performance Persons Phase Phenotype Plasma Prevention Primary carcinoma of the liver cells Race Recording of previous events Research Research Institute Research Personnel Resources Risk Sampling Screening for Hepatocellular Cancer Site Subgroup Testing Texas Time Tissues United States Department of Veterans Affairs Visit Work algorithm training alpha-Fetoproteins base blood-based biomarker cancer prevention case control cell free DNA clinical application clinical research site clinical risk cohort data harmonization design early detection biomarkers follow-up high risk improved indexing liquid biopsy liver imaging methylation biomarker mortality multidisciplinary non-alcoholic fatty liver disease novel novel marker phase 1 study phase 2 study phase 3 study phase 3 testing predictive modeling prospective racial and ethnic recruit risk prediction risk stratification sample collection translational impact translational scientist validation studies

项目摘要

The Translational Research Center (TRC) includes a multidisciplinary team of clinical and translational researchers that has a strong track record of collaborative work, with the collective mission of reducing the burden of HCC. At the center of the proposed TRC lie two unique active prospective (in-HCC surveillance) cohorts of patients with cirrhosis. One of the cohorts comes from a Cancer Prevention and Research Institute of Texas (CPRIT) funded ongoing prospective multicenter study (Texas HCC Consortium) that is on target to recruit > 3000 patients with cirrhosis (>12,000 surveillance episodes and 200 expected HCC cases) from diverse etiologies (including cured HCV and non-alcoholic fatty liver disease). These patients are under routine bi-annual surveillance at 5 medical centers in Texas. The second is a cohort of >700 patients (>1,300 visits surveillance episodes and 33 incident HCC cases as of September 2017) recruited from and prospectively followed at the Houston VA, most with cured HCV. The TRC will leverage, extend follow up, and harmonize data and samples from both cohorts, collectively resulting in a > 23,000 episodes of HCC surveillance (and > 300 expected HCC) with bio-banked specimens, clinical and radiological data for each episode, rendering it an invaluable resource for the proposed research and other trans-consortium projects. Using data from these cohorts, we will develop and test novel personalized risk stratification indices for predicting the future ‐ development to HCC in patients with cirrhosis across diverse etiologies (Aim 1). We will also develop and evaluate an early detection algorithm that combines existing HCC blood based biomarkers (e.g., AFP, AFP L3, DCP), their longitudinal changes over time and select host features (age, etiology) in a phase 3 study. We will also examine the performance of this algorithm in patients at different HCC risk strata (Aim 2). Our work will set the framework for incorporating other patient and liver disease related factors into (new) biomarker profiles, an area that is likely to remain highly relevant irrespective of the type of biomarker. We will evaluate highly promising methylated DNA markers (MDMs, liquid biopsy) as an independent test for HCC risk prediction in Aim 3. These markers have been identified in tissue case control phase 1 studies, reliable assays have been developed and they have excellent performance for HCC detection in phase 2 studies. We will validate individual markers in the study cohort and train an algorithm that combines the MDM to achieve maximum performance. In a phase 3 biomarker study, we will validate the algorithm in the test sample overall and in key subgroups based on HCC risk strata. Our approach (optimizing available markers while simultaneously maintaining a strong forward outlook) will have both an immediate and long-lasting impact on HCC related morbidity and mortality. The TRC will build on established and strong infra-structure and relationships to complete the proposed research. It also represents a new and exciting avenue for collaboration with other investigators within the U01 consortium.

转化研究中心 (TRC) 包括一个由临床和转化人员组成的多学科团队具有良好协作记录的研究人员，其集体使命是减少 HCC 的负担是拟议 TRC 的核心，有两个独特的主动前瞻性（HCC 内监测）。其中一组来自癌症预防和研究所的肝硬化患者。德克萨斯州 (CPRIT) 资助正在进行的前瞻性多中心研究（德克萨斯 HCC 联盟），其目标是招募 > 3000 名肝硬化患者（> 12,000 次监测和 200 例预期 HCC 病例）不同的病因（包括治愈的丙肝病毒和非酒精性脂肪肝）这些患者处于常规状态。第二个是在德克萨斯州 5 个医疗中心进行的每两年一次的监测，其中包括超过 700 名患者（超过 1,300 次就诊）。截至 2017 年 9 月的监测事件和 33 个 HCC 事件病例）是前瞻性招募的休斯敦退伍军人管理局紧随其后，大多数 HCV 已治愈，TRC 将利用、延长随访和协调。来自两个队列的数据和样本，总共产生了 > 23,000 次 HCC 监测（并且 > 300 个预期的 HCC）以及每个事件的生物库样本、临床和放射学数据，使其成为使用这些数据为拟议的研究和其他跨联盟项目提供宝贵的资源。我们将开发和测试新颖的个性化风险分层指数来预测未来 - 我们还将开发和研究不同病因的肝硬化患者发展为 HCC 的方法（目标 1）。评估结合现有 HCC 血液生物标志物（例如 AFP、AFP L3、 DCP），它们随时间的纵向变化，并在第 3 阶段研究中选择宿主特征（年龄、病因）。还检查了该算法在不同 HCC 风险层的患者中的表现（我们的工作将设定）。将其他患者和肝病相关因素纳入（新）生物标志物概况的框架，无论生物标志物的类型如何，我们都会高度评价这一领域。有前景的甲基化 DNA 标记（MDM、液体活检）作为 HCC 风险预测的独立测试目标 3. 这些标记物已在组织病例对照第一阶段研究中得到鉴定，可靠的测定已被证实已开发出来，并且它们在 2 期研究中具有出色的 HCC 检测性能。研究队列中的个体标记并训练结合 MDM 的算法以实现最大在第 3 阶段生物标志物研究中，我们将在测试样本中整体和关键地验证算法。基于 HCC 风险分层的亚组我们的方法（同时优化可用标记）。保持强烈的前瞻性）将对 HCC 相关领域产生直接和长期的影响 TRC 将建立在已建立的、强大的基础设施结构和关系的基础上。它也代表了与他人合作的新的、令人兴奋的途径。 U01财团内部的调查员。