Risk stratification strategies and abbreviated MRI-based surveillance for early detection of HCC in high-risk AI/AN patients

用于早期检测高危 AI/AN 患者 HCC 的风险分层策略和基于 MRI 的简化监测

• 批准号: 10286760
• 负责人: George Ioannou
• 金额: $ 26.26万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-06 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10286760
• 关键词: Alaska Native; American Indians; Biological; Categories; Cessation of life; Cirrhosis; Colorectal Cancer; Development; Early Diagnosis; Epidemiology; Face; Feasibility Studies; Foundations; Functional disorder; Genotype; HBV Genotype; Hepatitis B; Hepatitis B Virus; Incidence; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of liver; Malignant neoplasm of lung; Malignant neoplasm of prostate; Maps; Modeling; Mutation; Native-Born; Patients; Persons; Pilot Projects; Primary carcinoma of the liver cells; Protocols documentation; Randomized Controlled Trials; Reporting; Research; Risk; Risk Factors; Role; Testing; Time; Ultrasonography; Veterans Health Administration; Woman; base; cancer health disparity; clinically significant; cost effective; disparity elimination; high risk; imaging modality; improved; individual patient; innovation; machine learning algorithm; malignant breast neoplasm; men; mortality; novel; patient stratification; prospective; risk stratification; screening; surveillance strategy; translational approach

ABSTRACT: PROJECT 2. Risk Stratification and abbreviated MRI-based surveillance This translational project will first investigate further the clinical significance of an HCC pathogenetic mechanism that we described, which is particularly important in AI/AN patients, i.e. HBV genotype-specific mutations. We will then use AI/AN-specific HCC risk factors described by our group (including HBV genotype and genotype- specific mutations) to develop AI/AN-specific “HCC Risk Calculators” for HCC risk stratification and risk-based surveillance. Finally, we will use HCC Risk Calculators to identify high-risk patients for more intensive surveillance strategies using abbreviated MRI, which will be tested in a pilot and feasibility RCT. The project will accomplish the following specific aims: SA1. Investigate the role of genotype-specific HBV mutations in the development of HCC in Alaska Native patients: Determine the development of HBV genotype-specific mutations in AN patients with different HBV genotypes prior to the occurrence of HCC compared to appropriate controls without HCC, and the excess HCC risk associated with these mutations. SA2. Develop and validate “HCC Risk Calculators” in AI/AN patients with HBV or cirrhosis using biological and demographic predictors specific to AI/AN patients for the purpose of risk stratification, identification of high-risk patients and personalized HCC surveillance strategies. SA3. Perform a pilot and feasibility randomized controlled trial of abbreviated MRI (aMRI) versus ultrasonography (US) for HCC screening in 200 AI/AN patients who have high HCC risk. SIGNIFICANCE. This project will set the foundation for “precision HCC screening” based on estimating HCC risk in individual patients using HCC Risk Calculators, risk stratifying patients according to their HCC risk, and developing specific HCC surveillance strategies for different categories of HCC risk. This will be developed and pursued further in a subsequent P50 application

摘要：项目 2. 风险分层和基于 MRI 的简化监测 该转化项目将首先进一步研究 HCC 发病机制的临床意义 我们所描述的，这对于 AI/AN 患者尤其重要，即 HBV 基因型特异性突变。我们 然后将使用我们小组描述的 AI/AN 特异性 HCC 危险因素（包括 HBV 基因型和基因型） 特定突变）开发 AI/AN 特定的“HCC 风险计算器”，用于 HCC 风险分层和基于风险的 监视。最后，我们将使用 HCC 风险计算器来识别高风险患者，以进行更深入的治疗 使用简化 MRI 的监测策略，将在试点和可行性随机对照试验中进行测试。该项目将 实现以下具体目标： SA1。研究基因型特异性 HBV 突变在阿拉斯加原住民 HCC 发展中的作用 患者：确定患有不同 HBV 的 AN 患者中 HBV 基因型特异性突变的发展情况 与没有 HCC 的适当对照相比，HCC 发生前的基因型以及过量的 HCC 与这些突变相关的风险。 SA2。使用生物和方法开发并验证患有 HBV 或肝硬化的 AI/AN 患者的“HCC 风险计算器” 针对 AI/AN 患者的人口预测因子，用于风险分层、识别高风险 患者和个性化 HCC 监测策略。 SA3。对简化 MRI (aMRI) 与 对 200 名具有高 HCC 风险的 AI/AN 患者进行超声检查（美国）进行 HCC 筛查。 意义。该项目将为基于估计 HCC 的“精准 HCC 筛查”奠定基础 使用 HCC 风险计算器计算个体患者的风险，根据 HCC 风险对患者进行风险分层，以及 针对不同类别的 HCC 风险制定具体的 HCC 监测策略。这将被开发并 在随后的 P50 申请中进一步追求