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.

项目总结 肝细胞癌是美国增长最快的癌症死亡原因之一 预计到2040年将成为美国癌症死亡的第三大原因，因为目前的效果很差 肝细胞癌风险分层和早期发现策略。具体来说，建议对所有患者进行肝细胞癌筛查。 对于肝硬变，尽管每年的肝癌风险在1-4%/年之间，但突出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记物甲胎蛋白进行肝细胞癌筛查 (法新社)；然而，这一战略在早期阶段漏掉了三分之一以上的HC，并导致在 很多病人。我们的肝癌临床验证中心(CVC-HCC)的目标是验证新的血液和 I-III期研究中的成像生物标记物，以改善肝癌风险分层和早期发现。 由于缺乏高质量的样本集，肝细胞癌生物标记物的实践一直受到阻碍 包括储存的血液和成像。现有的样本集也主要包括活动性肝硬变患者。 病毒性肝炎，对主要治愈病毒性肝炎或 导致肝病的非病毒原因。我们的CVC将使用血液和成像数据创建当代资源 允许快速验证有前景的肝细胞癌生物标志物，在I-III期进行风险分层和早期检测 学习。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，超过四分之一的接受肝细胞癌筛查的患者有 发展为肝细胞癌的高风险，但不稳定(每年风险约为6-10%/年)。我们的团队确认了一种新的血液- 基于生物标记的PLSec用于风险分层，生物标记小组Galad用于患者的早期肝细胞癌检测 在此建议进行一项II-III期生物标记物研究，以评估ILNS患者的疗效。 我们的团队包括在肝细胞癌筛查、成像和生物标记物验证方面的国家领导者。我们正在带头努力 为了评估包括EDRN资助的肝细胞早期检测策略(HEDS)研究在内的肝细胞癌生物标志物， NCI资助的转化性肝癌(TLC)联盟和CPRIT资助的德克萨斯肝癌联盟。我们会 利用五个医疗系统中的现有基础设施创建两个新资源 目前的样本集包括(1)包含血液和成像数据的生物存储库，包括有无患者 肝癌，代表第二阶段研究的当代肝病病因和(2)预期队列 在第三阶段研究中，ILN患者评估肝细胞癌风险分层和早期检测生物标志物 前瞻性标本采集、回顾盲法评价(探针法)设计。我们将与国商合作 和DMCC评估新的生物标记物，促进对跨网络项目的贡献。总的来说，我们的CVC- 肝癌将在新生物标志物的I-III阶段验证方面取得重大进展，用于肝癌风险分层和 早期发现，这将促进设计良好的IV期临床实用试验的发展。