Abbreviated MRI for HCC screening in cirrhotic patients

项目摘要 肝细胞癌是美国增长最快的癌症死亡原因。近期 北美实践指南建议使用超声(US)进行半年一次的肝癌监测 无血清甲胎蛋白(AFP)用于肝硬变和其他高危患者，以允许在 早期，使有效的治疗成为可能，并有可能提高存活率。然而，美国受到的影响有限 肝硬变和超重/肥胖患者的表现，导致US对早期的敏感性 肝细胞癌低至40%。 我们最近构思并测试了一种新的缩写磁共振成像(AMRI)检查 包括注射加多沙酸后肝胆相的T1加权成像(T1-W) 专为检测肝硬变患者的肝细胞癌而设计，准确率更高，只有2个序列(t1-w HBP在20% 注射后最小时间和T2-w)。我们的初步数据表明，HBP-AMRI对肝癌的敏感度为80% 侦测。在这里，我们建议建立一个预期的多中心(由位于芒特山的伊坎医学院组成 西奈大学、加州大学圣地亚哥分校、威斯康星大学麦迪逊分校和杜克大学)学习 在820名美国人中评估HBP-AMRI作为早期发现肝癌的筛查手段的性能 患有肝硬变。完整的MRI(包括动态成像、HBP成像和其他序列)将 分解以重建HBP-AMRI考试。使用这个重建的考试，我们将测试我们的中央 假设HBP-AMRI在检测肝癌方面比US更敏感和更具成本效益。我们还将评估 循环肿瘤DNA(CtDNA)与血清甲胎蛋白联合检测的诊断价值 具体地说，我们的目标是确定：1)HBP-AMRI与US对肝癌的诊断性能 肝硬变患者的筛查。2)增加ctDNA和血清AFP的价值，以提高HBP-DNA对肝癌的检测 肝硬变患者的AMRI或US，3)HBP-AMRI与US在肝硬变肝细胞癌筛查中的成本-效果比较 病人。最后，我们将从完整的考试中重建一个加多西酸增强(Dyn-AMRI)考试 DYN-AMRI与HBP-AMRI及US在肝细胞癌筛查中的对比分析 我们的长期目标是验证一种准确和精确的方法来改进筛查和 监测有可能降低肝细胞癌死亡率的肝硬化患者的肝细胞癌。成功者 该提案的完成将有助于验证一种包含HBP-AMRI的新筛查方法，可能 结合ctDNA。

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.