Evaluation of HCC Response to Systemic Therapy with Quantitative MRI

定量 MRI 评估 HCC 对全身治疗的反应

基本信息

批准号：
8613479
负责人：
Bachir Taouli
金额：
$ 49.34万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-02-05 至 2018-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8613479
关键词：
Algorithms American Angiogenesis Inhibitors BAY 54-9085 Blood Vessels Brain Neoplasms Carbogen Cellularity Chemoembolization Chronic Hepatitis C Cirrhosis Clinical Country Data Data Quality Development Diffusion Diffusion weighted imaging Disease Progression Early treatment Evaluation Excision Fibrosis Gadolinium Goals Growth Health Health Care Costs Histologic Histopathology Human Hypoxia Image Incidence Infection Investigational Therapies Keratin-19 Liver Liver diseases Liver parenchyma Mammary Neoplasms Measurement Measures Metastatic Neoplasm to the Liver Methods Metric Modeling Molecular Molecular Target Monitor Morbidity - disease rate Motion Necrosis Outcome Oxygen Pathway interactions Patients Perfusion Perfusion Weighted MRI Pharmaceutical Preparations Play Primary carcinoma of the liver cells Prospective Studies Prostatic Neoplasms Quality Control Reaction Time Reproducibility Research Personnel Role Source Staging Stimulus System Systemic Therapy Techniques Testing Therapeutic Training Tumor Biology Tumor Markers United States Validation Vascular Endothelial Growth Factors Weight Work angiogenesis base blood oxygen level dependent blood perfusion density effective therapy experience gadolinium oxide hypoxia inducible factor 1 imaging modality improved liver imaging liver injury mortality non-invasive system novel outcome forecast research study response response marker screening tool tumor tumor progression uptake

项目摘要

DESCRIPTION (provided by applicant): The incidence of hepatocellular carcinoma (HCC) has recently increased in the United States. HCC is/will be the source of enormous health care costs and morbidity/mortality, and generally develops in patients with advanced liver damage (advanced fibrosis and cirrhosis). Although imaging plays a major role in HCC screening and staging, the possibility of predicting HCC tumor grade, aggressiveness, angiogenesis and hypoxia with imaging are unmet needs. In addition, new antiangiogenic drugs now available to treat advanced HCC necessitate the use of new imaging criteria beyond size. In this proposal, we would like to test and validate non invasive magnet resonance imaging (MRI) methods based on advanced diffusion-weighted imaging (intravoxel incoherent motion diffusion MRI: IVIM DWI), BOLD (blood oxygen level dependent) MRI and perfusion-weighted imaging (PWI, using gadolinium contrast) to be used as non invasive markers of major histopathologic features of HCC (grade, aggressiveness, angiogenesis and hypoxia), and to predict and assess early response of HCC to systemic therapy with sorafenib (systemic drug approved for use in advanced HCC). We also would like to develop quality control tools to improve the quality and decrease variability of these quantitative MRI metrics. Based on our recent preliminary data, we believe that DWI has potential for predicting HCC tumor grade, and HCC response to locoregional therapy; and that BOLD MRI and PWI can be used to quantify degree of vascularity and lack of oxygen supply (hypoxia) in HCC, which are important tumor markers, and could be used as early markers of response to sorafenib. Ultimately, we are hoping to validate a novel non invasive algorithm based on multiparametric MRI to predict response of HCC to sorafenib, and to predict prognosis. These methods could become useful tools for testing new antiangiogenic drugs and experimental therapies in HCC, will enable individualized therapy, and provide prognosis in patients with HCC. This will be a highly significant progress in HCC and liver diseases given the increased burden of HCC in this country, and would benefit a large number of Americans over the next decade.

描述（由申请人提供）：美国最近在美国增加了肝细胞癌（HCC）的发病率。 HCC是/将是巨大的医疗保健成本和发病率/死亡率的来源，并且通常在肝脏损伤（晚期纤维化和肝硬化）的患者中发展。尽管成像在HCC筛查和分期中起主要作用，但预测HCC肿瘤等级，攻击性，血管生成和成像缺氧的可能性是未满足的需求。此外，现在可用于治疗高级HCC的新型抗血管生成药物必须使用超出大小的新成像标准。在此提案中，我们希望基于高级扩散加权成像（Intravoxel Increrhent运动扩散MRI：IVIM DWI），大胆（血氧级依赖）MRI和MRI和灌注量，测试和验证非侵入性磁铁共振成像（MRI）方法（MRI）方法成像（PWI，使用Gadolinium对比度）用作HCC的主要组织病理学特征的非侵入性标记（等级，侵略性，血管生成和缺氧），并预测HCC对使用Sorafenib的全身治疗的早期反应（已批准Sorafenib的全身药物批准用于高级HCC）。我们还想开发质量控制工具，以提高这些定量MRI指标的质量和降低。根据我们最近的初步数据，我们认为DWI具有预测HCC肿瘤等级的潜力以及对局部疗法的HCC反应。大胆的MRI和PWI可用于量化HCC中的血管性程度和缺氧（缺氧），这是重要的肿瘤标记，可以用作对索拉非尼的反应的早期标记。最终，我们希望验证一种基于多参数MRI的新型非浸润算法，以预测HCC对索拉非尼的反应并预测预后。这些方法可能成为测试新的抗血管生成药物和HCC中实验疗法的有用工具，可以实现个性化疗法，并为HCC患者提供预后。鉴于该国HCC的负担增加，这将是HCC和肝病疾病的巨大进展，并且在未来十年内将使许多美国人受益。