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.

项目概要 肝细胞癌 (HCC) 是美国增长最快的癌症死亡原因之一， 鉴于目前的治疗效果不佳，预计到 2040 年，癌症将成为美国第三大癌症死亡原因 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 患有肝硬化，尽管年度 HCC 风险在 1-4% 之间变化，这凸显了风险分层的必要性 生物标志物。使用腹部超声和血清生物标志物甲胎蛋白进行 HCC 筛查 （法新社）；然而，这一策略在早期阶段错过了超过三分之一的 HCC，并导致筛查危害 很多病人。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 期研究中对生物标志物进行成像，以改善 HCC 风险分层和早期检测。 由于缺乏高质量样本集，HCC 生物标志物转化为实践受到了阻碍，其中包括 两者都储存血液和成像。现有样本集还主要包括因活动性肝硬化患者 病毒性肝炎，对主要治愈病毒性肝炎或的当代人群的适用性有限 肝病的非病毒原因。我们的 CVC 将利用血液和影像数据创建当代资源，以 允许快速验证有前景的生物标志物，用于 HCC 风险分层和 I-III 期早期检测 研究。需要更好生物标志物的特定人群是患有不确定肝结节 (ILN) 的患者 诊断性 CT 或 MRI，在超过四分之一接受 HCC 筛查的患者中观察到，并且具有 发展为 HCC 的风险较高，但变化较大（年风险约为 6-10%/年）。我们的小组验证了一种新型血液- 基于生物标记物 PLSec，用于风险分层；生物标记物组 GALAD，用于患者早期 HCC 检测 肝硬化患者，本文建议进行 II-III 期生物标志物研究，以在 ILN 患者中评估它们。 我们的团队包括 HCC 筛查、成像和生物标志物验证领域的国家领导者。我们正在引领努力 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 资助的转化性肝癌 (TLC) 联盟和 CPRIT 资助的德克萨斯 HCC 联盟。我们将 利用五个卫生系统的现有基础设施来创建两种新资源 当前的样本集包括（1）一个生物储存库，其中包含患者的血液和成像数据，无论是否患有 HCC，代表 II 期研究的当代肝病病因学，以及 (2) 前瞻性队列 使用 ILN 患者在 III 期研究中评估 HCC 风险分层和早期检测生物标志物 前瞻性样本采集、回顾性盲法评估（PRoBE）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 将导致 HCC 风险分层和新型生物标志物的 I-III 期验证取得重大进展 早期检测，这将有助于开发精心设计的 IV 期临床实用试验。