Precision Risk Stratification and Screening for HCC among Patients with Indeterminate Liver Nodules

不确定肝结节患者的精准风险分层和 HCC 筛查

• 批准号: 10736885
• 负责人: Yujin Hoshida
• 金额: $ 90.72万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-19 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10736885
• 关键词: Abbreviations; Abdomen; Absenteeism at work; Address; American; Anxiety; Benign; Biological Markers; Biopsy; Blood; Cancer Etiology; Center for Translational Science Activities; Cessation of life; Cirrhosis; Classification; Clinical; Cohort Studies; Complement; Data; Detection; Diagnosis; Diagnostic; Early Detection Research Network; Early Diagnosis; Evaluation; Facilities and Administrative Costs; Funding; Goals; Harm Reduction; Image; Infrastructure; Lead; Literature; Liver; Liver diseases; Magnetic Resonance Imaging; Malignant neoplasm of liver; Meta-Analysis; Methodology; Modeling; NCI Center for Cancer Research; National Cancer Institute; Nodule; Outcome; Patient Recruitments; Patients; Phase; Primary carcinoma of the liver cells; Radiation exposure; Recommendation; Risk; Series; Serum; Site; Specific qualifier value; Standardization; Study models; System; Testing; Validation; Variant; Work; alpha-Fetoproteins; biomarker panel; biomarker validation; blood-based biomarker; clinical practice; cohort; comparative cost effectiveness; contrast enhanced; cost; cost effective; cost effectiveness; cost-effectiveness evaluation; effectiveness evaluation; effectiveness validation; evidence base; experience; high risk; high risk population; imaging biomarker; improved; individual patient; liver cancer model; models and simulation; novel; novel marker; patient oriented; performance tests; personalized care; personalized screening; precision medicine; programs; psychologic; recruit; risk stratification; screening; surveillance strategy; translational cancer research; tumor; ultrasound

PROJECT SUMMARY Large gaps in current strategies for risk stratification and surveillance contribute to frequent late-stage detection and poor outcomes in patients with hepatocellular carcinoma (HCC). Our Translational Liver Cancer (TLC) Research Center has made important scientific contributions that directly addressed HCC risk stratification and surveillance in patients with cirrhosis. Specifically, we conducted a series of phase II and phase III biomarker studies in patients with cirrhosis to validate 1) the first blood-based biomarker for risk stratification (PLSec-AFP), 2) abbreviated MRI for HCC surveillance, and 3) two biomarker panels, GALAD and Doylestown Plus for HCC surveillance. We also conducted modeling studies to evaluate how these data can be incorporated into clinical practice, evaluating the cost-effectiveness of a precision surveillance strategy in these patients. For our TLC renewal, we leverage our infrastructure and operational expertise to similarly develop an optimized, evidence-based approach to early HCC detection in patients with indeterminate liver nodules (ILNs). Our preliminary data demonstrate that patients with ILNs have an annual HCC risk of 6-10%/year, more than double that of those with cirrhosis without ILNs; however, they experience wide variation in HCC risk and surveillance strategies – with some patients who develop HCC failing to undergo surveillance in the year prior to diagnosis and some patients undergoing repeated CT/MRI-based surveillance despite never developing HCC. Our work highlights the need for accurate risk stratification and surveillance strategies in patients with ILNs to optimize the overall value of early HCC detection programs – gaps that are directly addressed by our proposal. We will leverage our Early Detection Research Network (EDRN)-funded Clinical Validation Center for HCC to efficiently recruit a large cohort of patients with ILNs and (1) validate the effectiveness of a novel biomarker- based risk stratification model, (2) evaluate the effectiveness of surveillance abbreviated MRI and contrast enhanced ultrasound for detecting early-stage HCC, and (3) compare the cost effectiveness of surveillance strategies including a precision screening model in patients with ILNs. Our proposal aligns with the principles of precision medicine and would maximize benefits (via early tumor detection) and minimize harms (via false positive results) for each patient, thereby optimizing the patient- centeredness, cost effectiveness, and overall value of HCC surveillance in patients with ILNs. In addition to our patient cohorts and platform of unique biomarker and imaging data, our TLC research center will contribute methodological expertise in HCC early detection, biomarker validation, and HCC imaging to trans-network projects. Overall, our proposal will transform our approach to early HCC detection in patients with ILNs by validating evidence-based and cost-effective strategies to optimize HCC risk stratification and surveillance.

项目概要 当前风险分层和监测策略存在巨大差距，导致频繁的后期检测 肝细胞癌（HCC）患者预后不佳。我们的转化性肝癌 (TLC) 研究中心做出了重要的科学贡献，直接解决了 HCC 风险分层和 肝硬化患者的监测。具体来说，我们进行了一系列 II 期和 III 期生物标志物 在肝硬化患者中进行的研究旨在验证 1) 第一个用于风险分层的血液生物标志物 (PLSec-AFP)， 2) 用于 HCC 监测的简化 MRI，以及 3) 用于 HCC 的两个生物标记物组，GALAD 和 Doylestown Plus 监视。我们还进行了建模研究，以评估如何将这些数据纳入临床 实践，评估这些患者的精确监测策略的成本效益。 对于 TLC 更新，我们利用我们的基础设施和运营专业知识来类似地开发优化的、 对不确定肝结节 (ILN) 患者进行早期 HCC 检测的循证方法。我们的 初步数据表明，ILN 患者每年发生 HCC 的风险为 6-10%，是其两倍多 没有 ILN 的肝硬化患者的情况；然而，他们的 HCC 风险和监测存在很大差异 策略 – 一些患有 HCC 的患者在诊断前一年未能接受监测 一些患者尽管从未发展为 HCC，但仍接受了基于 CT/MRI 的重复监测。我们的工作 强调需要对 ILN 患者进行准确的风险分层和监测策略，以优化治疗 早期 HCC 检测计划的总体价值——我们的提案直接解决了这些差距。 我们将利用我们的早期检测研究网络 (EDRN) 资助的 HCC 临床验证中心来 有效招募大量 ILN 患者并 (1) 验证新型生物标志物的有效性 基于风险分层模型，（2）评估监测简化MRI和对比的有效性 增强超声检测早期 HCC，以及 (3) 比较监测的成本效益 策略包括对 ILN 患者进行精确筛查模型。 我们的建议符合精准医学的原则，并将最大化效益（通过早期肿瘤 检测）并最大限度地减少对每个患者的伤害（通过假阳性结果），从而优化患者- ILN 患者 HCC 监测的中心性、成本效益和总体价值。除了我们的 我们的 TLC 研究中心将贡献患者队列和独特生物标志物和成像数据平台 HCC 早期检测、生物标志物验证和跨网络 HCC 成像方面的方法学专业知识 项目。总体而言，我们的提案将通过以下方式改变我们对 ILN 患者进行早期 HCC 检测的方法： 验证基于证据且具有成本效益的策略，以优化 HCC 风险分层和监测。