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：
8422564
负责人：
Bachir Taouli
金额：
$ 54.46万
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/8422564
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 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）：肝细胞癌（HCC）的发病率最近在美国有所增加。 HCC 是/将会是巨大的医疗保健费用和发病率/死亡率的根源，并且通常发生在患有晚期肝损伤（晚期纤维化和肝硬化）的患者中。尽管影像学在 HCC 筛查和分期中发挥着重要作用，但通过影像学预测 HCC 肿瘤分级、侵袭性、血管生成和缺氧的可能性尚未得到满足。此外，现在可用于治疗晚期 HCC 的新抗血管生成药物需要使用超越尺寸的新成像标准。在本提案中，我们希望测试和验证基于先进扩散加权成像（像素内不相干运动扩散 MRI：IVIM DWI）、BOLD（血氧水平依赖）MRI 和灌注加权的非侵入性磁共振成像（MRI）方法成像（PWI，使用钆对比）用作 HCC 主要组织病理学特征（分级、侵袭性、血管生成和缺氧）的非侵入性标志物，并进行早期预测和评估HCC 对索拉非尼（批准用于晚期 HCC 的全身药物）全身治疗的反应。我们还希望开发质量控制工具来提高这些定量 MRI 指标的质量并减少变异性。根据我们最近的初步数据，我们相信 DWI 有潜力预测 HCC 肿瘤分级以及 HCC 对局部治疗的反应； BOLD MRI 和 PWI 可用于量化 HCC 中血管分布和供氧不足（缺氧）的程度，这些是重要的肿瘤标志物，并可用作索拉非尼反应的早期标志物。最终，我们希望验证一种基于多参数 MRI 的新型非侵入性算法，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 实验疗法的有用工具，使个体化治疗成为可能，并为 HCC 患者提供预后。鉴于美国 HCC 负担的增加，这将是 HCC 和肝脏疾病方面的一项非常重大的进展，并将在未来十年造福大量美国人。