Liquid biopsy and radiomics for liver cancer surveillance

摘要 肝细胞癌（HCC）是美国增长最快的癌症死亡原因。而 尽管预防工作至关重要，但大多数患者死于晚期HCC疾病。故，在《易经》中， 风险患者（例如，任何病因的肝硬化）的早期检测计划，建议在临床实践中 指南改善早期HCC检测的长期挑战是 建议的监测工具[即，腹部超声和血清甲胎蛋白（AFP）]和 监测项目实施率低（美国低至25%）。各种研究 试图利用释放到血流中的肿瘤核酸（即，“液体活检”）作为新的早期HCC 检测工具，但其在这种临床环境中的作用在很大程度上是未开发的。高达18%的肝硬化患者 监测期间发现的不确定结节。在这些患者中，成像是不确定的，患者 需要对可疑结节进行活检和/或密切的成像随访。 我们的项目旨在通过使用新的基于血液的液体活检生物标志物来克服这些问题， 基于磁共振成像（MRI）的放射组学。我们已经组建了一个多机构的翻译 研究中心包括纽约市领先的学术中心（西奈山，哥伦比亚，康奈尔大学和蒙特菲奥雷）。 我们计划从2,560例多种族患者（早期HCC病例）中收集血液、临床和影像学数据 高风险控制）。在目标1中，我们将确定新的液体活检技术的临床作用（即， 无细胞DNA片段分析和来自血浆中细胞外囊泡的3-小RNA特征）作为 HCC的新监测方法。在目标2中，我们将基于MRI的放射组学模型与我们的液体 活检技术，以更好地表征肝硬化中的不确定结节。我们的项目是及时和独特的 准备响应开发早期HCC检测的非侵入性生物标志物的必要性。

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.