Liquid biopsy and radiomics for liver cancer surveillance

用于肝癌监测的液体活检和放射组学

• 批准号: 10736720
• 负责人: Bachir Taouli
• 金额: $ 72.04万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 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/10736720
• 关键词: Abdomen; Ablation; Acceleration; Address; Adoption; Benign; Biological Markers; Biopsy; Blood; Blood Circulation; Breakthrough device; Cancer Etiology; Cancerous; Center for Translational Science Activities; Cessation of life; Cirrhosis; Clinical; Clinical Data; Clinical Practice Guideline; Collaborations; Collection; Data; Descriptor; Detection; Development; Diagnosis; Disease; Early Diagnosis; Enrollment; Ensure; Etiology; Evaluation; Goals; Guidelines; Image; Institution; Laboratories; Lesion; Liver; Machine Learning; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of liver; Malignant neoplasm of lung; Marketing; Measures; Methods; Modeling; Molecular; New York; Nodule; Nomograms; Notification; Nucleic Acids; Operative Surgical Procedures; Patients; Performance; Phase; Plasma; Populations at Risk; Positioning Attribute; Prevention; Primary carcinoma of the liver cells; Probability; Prospective cohort; Radiology Specialty; Recommendation; Reproducibility; Resources; Risk; Role; Sampling; Sensitivity and Specificity; Serum; Small RNA; Surveillance Program; Technology; Testing; Training; United States; Validation; Vesicle; accurate diagnosis; alpha-Fetoproteins; biobank; blood-based biomarker; cell free DNA; cohort; curative treatments; design; diagnostic value; early detection biomarkers; extracellular vesicles; follow-up; high risk; high risk population; improved; liquid biopsy; magnetic resonance imaging biomarker; member; multi-racial; novel; overtreatment; patient population; programs; radiomics; technology validation; tool; tumor; ultrasound

ABSTRACT Hepatocellular carcinoma (HCC) is the fastest growing cause of cancer death in the United States. While prevention efforts are paramount, most patients succumb to advanced HCC disease. Thus, enrollment of at- risk patients (e.g., cirrhosis of any etiology) in early detection programs is recommended in clinical practice guidelines. Longstanding challenges to improving early-stage HCC detection are suboptimal performance of the recommended surveillance tools [i.e., abdominal ultrasound and serum alpha-fetoprotein (AFP)] and the low implementation rate of surveillance programs (as low as 25% in the United States). Various studies have tried to utilize tumor nucleic acids released to the bloodstream (i.e., “liquid biopsy”) as novel early HCC detection tools, but its role in this clinical setting is largely unexplored. Up to 18% of patients with cirrhosis have indeterminate nodules detected during surveillance. In these patients, imaging is inconclusive, and patients require either a biopsy of the suspicious nodule and/or close imaging follow-up. Our project is designed to overcome these problems by using new blood-based liquid biopsy biomarkers and magnetic resonance imaging (MRI)-based radiomics. We have assembled a multi-institutional Translational Research Center including leading academic centers in NYC (Mount Sinai, Columbia, Cornell, and Montefiore). We plan to collect blood, clinical and imaging data from a multiracial cohort of 2,560 patients (early HCC cases and controls at high risk). In Aim 1, we will determine the clinical role of new liquid biopsy technologies (i.e., cell-free DNA fragment analysis and a 3-small RNA signatures from extracellular vesicles in plasma) as a novel surveillance approach in HCC. In Aim 2, we will integrate MRI-based radiomics models with our liquid biopsy technologies to better characterize indeterminate nodules in cirrhosis. Our project is timely and uniquely poised to respond to the imperative of developing noninvasive biomarkers of early HCC detection.

抽象的 肝细胞癌（HCC）是美国癌症死亡最快的原因。尽管 预防工作至关重要，大多数患者屈服于晚期HCC疾病。那是AT-的注册 在临床实践中，建议在早期检测计划中使用风险患者（例如，任何病因的肝硬化） 指南。改善早期HCC检测的长期挑战是次优表现 推荐的监视工具[即腹部超声和血清α-抗蛋白蛋白（AFP）]和 监视计划的实施率低（在美国低至25％）。各种研究 试图利用释放到血液的肿瘤核酸（即“液体活检”）作为新型早期HCC 检测工具，但在这种临床环境中的作用在很大程度上是出乎意料的。多达18％的肝硬化患者患有 监视过程中检测到的不确定结节。在这些患者中，成像尚无定论，患者 需要对可疑结节和/或关闭成像随访的活检。 我们的项目旨在通过使用新的血液液体活检生物标志物和 磁共振成像（MRI）基于放射线学。我们组装了多机构的翻译 研究中心，包括纽约市的主要学术中心（西奈山，哥伦比亚，康奈尔和蒙特菲奥尔）。 我们计划从2,560例患者（早期HCC病例）的多种族组中收集血液，临床和成像数据 控制高风险）。在AIM 1中，我们将确定新的液体活检技术的临床作用（即 无细胞的DNA片段分析和来自等离子体细胞外蔬菜的3小小的RNA特征） HCC中的新型监视方法。在AIM 2中，我们将将基于MRI的放射线学模型与我们的液体集成 活检技术以更好地表征肝硬化中不确定的结节。我们的项目及时且独特 准备应对早期HCC检测的无创生物标志物的当务之急。