Blood-Based Testing for Advanced Adenoma

项目摘要/摘要 我们的临床验证中心(CVC)的目标是推进和验证基于血液的结直肠检测 晚期腺瘤。而侵袭性结直肠癌的血液检测正在取得进展，有多个 公司追求产品，基于血液的检测能力，以检测晚期腺瘤，前 最接近浸润性癌症的恶性病变，是不确定的。为了最大限度地影响结直肠癌发病率， 基于血液的生物标记物不只是检测癌症，它们还应该具有足够的灵敏度来识别 患有晚期腺瘤的受试者。对于我们的CVC，我们组织和组装了一个高度熟练的网络 临床中心，包括专注于少数族裔人群，以期收集具有良好特征的、高度集中的 大量晚期腺瘤患者接受手术前的高质量血液样本 息肉切除术和息肉切除术后的序贯治疗。从相同的临床中心，我们将收集血液样本 来自对照受试者。将使用标准协议收集和处理标本，并与 人口统计和临床变量将被捕获，以促进生物标志物验证研究。具体来说，我们 将使用这些特征良好的样本来验证我们关于原创、创新技术的效用的数据 用于晚期腺瘤的分子检测，包括RealSeqS与定制机器的结合 学习信号等算法。我们提出了两个具体目标。在具体目标1中，我们将进行一个阶段 2病例对照研究，以验证我们先进的腺瘤检测新方法。我们将前瞻性地 招募晚期腺瘤患者(N=400)和特定部位对照组(N=400)进行比较 案件的主题。在具体目标2中，我们将利用系统收集的后续连续血液样本。 从我们的病例对象中切除息肉以确定我们的新分子检测技术是否可以 用于预测复发的可能性，并潜在地指导监视结肠镜检查。进阶 腺瘤是非侵袭性结直肠癌筛查的下一个重要前沿，我们的CVC是 配备先进的血液检测进展期腺瘤。

PROJECT SUMMARY/ABSTRACT The goal of our Clinical Validation Center (CVC) is to advance and validate blood-based detection of colorectal advanced adenoma. Whereas blood-based testing for invasive colorectal cancer is progressing, with multiple companies pursuing products, the ability of blood-based testing to detect advanced adenomas, the pre- malignant lesions closest to invasive cancer, is uncertain. To optimally impact colorectal cancer incidence, blood-based biomarkers cannot just detect cancer, they should also have sufficient sensitivity to identify subjects with advanced adenomas. For our CVC, we organized and assembled a network of highly skilled clinical centers including a focus on minority populations, to prospectively collect well-characterized, high- quality blood specimens from a large number of subjects with advanced adenoma prior to undergoing polypectomy and serially post-polypectomy. From the same clinical centers, we will collect blood specimens from control subjects. Specimens will be collected and processed using standard protocols, and relevant demographic and clinical variables will be captured to facilitate biomarker validation studies. Specifically, we will use these well-characterized specimens to validate our data on the utility of original, innovative techniques for molecular detection of advanced adenomas including RealSeqS in combination with custom machine learning algorithms such as SignaL. We propose two Specific Aims. In Specific Aim 1, we will conduct a phase 2 case-control study to validate our novel methods for advanced adenoma detection. We will prospectively recruit patients with advanced adenoma (N=400) and site-specific control subjects (N=400) for comparison to the case subjects. In Specific Aim 2, we will utilize serial blood specimens systematically collected post- polypectomy from our case subjects to determine whether our novel molecular detection techniques can be used to predict likelihood of recurrence and potentially guide surveillance colonoscopy exams. Advanced adenomas are the important, next frontier in non-invasive colorectal cancer screening, and our CVC is equipped to profoundly advance blood-based detection of advanced adenoma.