Clinical Validation Center for Hepatocellular Carcinoma

肝细胞癌临床验证中心

• 批准号: 10676320
• 负责人: FASIHA KANWAL
• 金额: $ 104.14万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-03 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10676320
• 关键词: Abdomen; Area; Biological Markers; Blinded; Blood; Cancer Etiology; Cessation of life; Cirrhosis; Clinical; Data; Detection; Development; Diagnostic; Early Detection Research Network; Early Diagnosis; Effectiveness; Etiology; Evaluation; Funding; Future; Goals; Guidelines; Health system; Heterogeneity; Image; Infrastructure; Liver; Liver diseases; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of liver; Modeling; Molecular Profiling; Nodule; Patients; Performance; Phase; Policies; Population; Primary Malignant Neoplasm of Liver; Primary carcinoma of the liver cells; Prospective cohort; Radiology Specialty; Recommendation; Resources; Risk; Risk Factors; Sampling; Serum; Testing; Texas; Translations; Validation; Viral hepatitis; Work; alpha-Fetoproteins; biobank; biomarker discovery; biomarker panel; biomarker validation; blood-based biomarker; clinical practice; clinical risk; cohort; curative treatments; design; early detection biomarkers; ethnic minority; high risk; imaging biomarker; imaging study; improved; novel; novel marker; patient population; patient stratification; phase 2 study; phase 3 study; prospective; racial minority; radiological imaging; radiomics; risk stratification; sample collection; screening; tumor; ultrasound; validation studies

PROJECT SUMMARY Hepatocellular carcinoma (HCC) is one of the fastest-growing cause of cancer death in the U.S. and it is projected to be the 3rd leading cause of cancer death in the U.S. by 2040 given the poor effectiveness of current HCC risk stratification and early detection strategies. Specifically, HCC screening is recommended in all patients with cirrhosis, despite annual HCC risk varying between 1-4%/year, highlighting a need for risk stratification biomarkers. HCC screening is performed using abdominal ultrasound and the serum biomarker alpha fetoprotein (AFP); however, this strategy misses over one-third of HCCs at an early stage and results in screening harms in many patients. The goal of our Clinical Validation Center for HCC (CVC-HCC) is to validate novel blood and imaging biomarkers in phase I-III studies to improve HCC risk stratification and early detection. Translation of HCC biomarkers to practice has been hampered by a dearth of high-quality sample sets including both stored blood and imaging. Existing sample sets also primarily include patients with cirrhosis from active viral hepatitis, with limited applicability to contemporary populations who primarily have cured viral hepatitis or non-viral causes of liver disease. Our CVC will create a contemporary resource with blood and imaging data to allow for rapid validation of promising biomarkers for HCC risk-stratification and early detection in phase I-III studies. A specific population in need of better biomarkers is patients with indeterminate liver nodules (ILNs) on diagnostic CT or MRI, which are observed in over one-fourth of patients undergoing HCC screening and have a high, yet variable, risk for developing into HCC (annual risk ~6-10%/year). Our group has validated a novel blood- based biomarker, PLSec, for risk stratification and a biomarker panel, GALAD, for early HCC detection in patients with cirrhosis and herein propose to perform a phase II-III biomarker study to evaluate them in patients with ILNs. Our team includes national leaders in HCC screening, imaging, and biomarker validation. We are leading efforts to evaluate HCC biomarkers including the EDRN-funded Hepatocellular Early Detection Strategy (HEDS) Study, NCI-funded Translational Liver Cancer (TLC) Consortium, and CPRIT-funded Texas HCC Consortium. We will leverage existing infrastructure across five health systems to create two novel resources not offered by the current sample sets including (1) a biorepository with both blood and imaging data from patients, with and without HCC, representing contemporary etiologies of liver disease for Phase II studies and (2) a prospective cohort of patients with ILNs to evaluate HCC risk stratification and early detection biomarkers in Phase III studies using a prospective-specimen-collection, retrospective-blinded-evaluation (PRoBE) design. We will work with the BCCs and DMCC to evaluate novel biomarkers, facilitating contributions to trans-network projects. Overall, our CVC- HCC will lead to significant advances in phase I-III validation of novel biomarkers for HCC risk stratification and early detection, areas of need that will facilitate development of well-designed phase IV clinical utility trials.

项目摘要 肝细胞癌（HCC）是美国癌症死亡最快的原因之一，是 鉴于当前的有效性较差 HCC风险分层和早期检测策略。具体而言，建议所有患者进行HCC筛查 肝硬化，尽管HCC风险在每年1-4％之间变化，但强调了风险分层的需求 生物标志物。使用腹部超声和血清生物标志物α胎蛋白进行HCC筛查 （法新社）;但是，这种策略在早期阶段遗漏了超过三分之一的HCC，并导致筛查危害 许多患者。我们的HCC临床验证中心（CVC-HCC）的目标是验证新型血液和 在I-III期研究中成像生物标志物，以改善HCC风险分层和早期检测。 hcc生物标志物的翻译为实践，这受到了缺乏高质量样本的缺乏 都存储了血液和成像。现有样品集还主要包括活跃的肝硬化患者 病毒肝炎，对主要治愈病毒肝炎或 肝病的非病毒原因。我们的CVC将创建一个具有血液和成像数据的现代资源 允许快速验证有希望的生物标志物进行HCC风险分层和II-III期间的早期检测 研究。需要更好生物标志物的特定人群是不确定的肝结节（ILN）的患者 诊断CT或MRI，在超过四分之一的患者进行HCC筛查中观察到，并且具有 高，但可变的风险会发展为HCC（每年风险约为6-10％）。我们的小组已经验证了一种新颖的血液 - 基于生物标志物PLSEC，用于风险分层和生物标志物面板，galad，用于患者的早期HCC检测 肝硬化和此处提议进行II-III期生物标志物研究，以评估ILNS患者。 我们的团队包括HCC筛查，成像和生物标志物验证的国家领导者。我们是领导努力 评估HCC生物标志物，包括EDRN资助的肝细胞早期检测策略（HEDS）研究， NCI资助的转化肝癌（TLC）财团和CPRIT资助的德克萨斯州HCC财团。我们将 利用五个卫生系统的现有基础设施来创建两个不提供的新型资源 当前的样本集，包括（1）具有血液和来自患者的血液和成像数据的生物库，有或没有 HCC，代表II期研究的肝病的当代病因，（2） III期研究中ILN的患者评估HCC风险分层和早期检测生物标志物 前瞻性特异性收集，回顾性盲评（探针）设计。我们将与BCC合作 和DMCC评估新型生物标志物，促进对跨网络项目的贡献。总体而言，我们的CVC- HCC将在II-III期验证的新型生物标志物方面取得重大进展，用于HCC风险分层和 早期检测，需要促进精心设计的IV期临床实用试验的需求领域。