Abbreviated MRI for HCC screening in cirrhotic patients

项目摘要 肝细胞癌（HCC）是美国增长最快的癌症死亡原因。最近 北美实践指南建议每半年使用超声（US）进行HCC监测， 不含血清甲胎蛋白（AFP）的患者，以允许检测HCC， 早期阶段，使有效的治疗，并可能提高生存。然而，美国受到有限的 在肝硬化和超重/肥胖患者中的表现，导致US对早期 HCC低至40%。 我们最近构思并测试了一种新的简化磁共振成像（AMRI）检查 包括钆塞酸注射后肝胆期的T1加权成像（T1-w）（HBP-AMRI） 设计用于检测肝细胞癌患者，提高准确性，仅使用2个序列（T1-w HBP为20 注射后1 min和T2-w）。我们的初步数据表明HBP-AMRI对HCC的敏感性> 80 侦测在这里，我们提出了一个前瞻性的多中心（由伊坎医学院在山 西奈、加州大学、圣地亚哥、威斯康星大学麦迪逊分校和杜克大学）留学，以 在820名美国人中评估HBP-AMRI作为早期发现HCC的筛查方式的性能 肝硬化将进行完整的MRI（包括动态成像、HBP成像和其他序列）， 分解重建HBP-AMRI考试。使用这个重建的考试，我们将测试我们的中心 假设HBP-AMRI在HCC检测中比US更敏感且成本效益更高。我们亦会评估 循环肿瘤DNA（ctDNA）和血清AFP的增量诊断价值。 具体来说，我们的目标是确定：1）HBP-AMRI与US对HCC的诊断性能 筛查糖尿病患者2)ctDNA和血清AFP对提高HBP检测HCC的附加值- AMRI或US在肝硬化患者中的应用，3）HBP-AMRI与US在肝硬化患者中用于HCC筛查的成本效益 患者最后，我们将从完整的检查中重建钆塞酸增强（Dyn-AMRI）检查， Dyn-AMRI与HBP-AMRI和US用于HCC筛查的诊断性能的探索性分析。 我们的长期目标是验证一种准确和精确的方法，以改善筛选和 监测肝硬化患者的HCC，可能降低HCC的死亡率。成功 完成这项建议将有助于验证一种新的筛选方法，包括HBP-AMRI，可能 与ctDNA结合。

Project Summary Hepatocellular carcinoma (HCC) is the fastest growing cause of cancer death in the United States. Recent North American practice guidelines recommend semi-annual HCC surveillance using ultrasound (US) with or without serum alpha-fetoprotein (AFP) for cirrhotic and other high-risk patients to permit detection of HCC at an early stage, enabling effective treatment, and potentially improving survival. However, US suffers from limited performance in patients with cirrhosis and overweight/obesity, causing the sensitivity of US for early-stage HCC to be as low as 40%. We recently conceived and tested a novel abbreviated magnetic resonance imaging (AMRI) exam including T1-weighted imaging (T1-w) at the hepatobiliary phase post gadoxetic acid injection (HBP-AMRI) designed to detect HCC in cirrhotic patients with improved accuracy, with only 2 sequences (T1-w HBP at 20 min post injection and T2-w). Our preliminary data suggest that HBP-AMRI provides >80% sensitivity for HCC detection. Here, we propose a prospective multicenter (composed of the Icahn School of Medicine at Mount Sinai, University of California, San Diego, University of Wisconsin-Madison and Duke University) study to assess the performance of HBP-AMRI as a screening modality for early detection of HCC in 820 Americans with cirrhosis. A complete MRI (which includes dynamic imaging, HBP imaging, and other sequences) will be disaggregated to reconstruct an HBP-AMRI exam. Using this reconstructed exam, we will test our central hypothesis that HBP-AMRI is more sensitive and cost-effective than US for HCC detection. We will also assess the incremental diagnostic value of circulating tumor DNA (ctDNA) and serum AFP. Specifically, we aim to determine the: 1) diagnostic performance of HBP-AMRI vs. US for HCC screening in cirrhotic patients. 2) added value of ctDNA and serum AFP for improving HCC detection by HBP- AMRI or US in cirrhotic patients, 3) cost-effectiveness of HBP-AMRI versus US for HCC screening in cirrhotic patients. Finally, we will reconstruct a gadoxetic acid-enhanced (Dyn-AMRI) exam from the complete exam for exploratory analyses of the diagnostic performance of Dyn-AMRI vs HBP-AMRI and US for HCC screening. Our long-term objective is to validate an accurate and precise method for improving the screening and surveillance for HCC in patients with cirrhosis, with potential mortality reduction from HCC. The successful completion of this proposal will help validate a novel screening method comprising HBP-AMRI, possibly combined with ctDNA.