MRI Biomarkers of Response in Cerebral Tumors

脑肿瘤反应的 MRI 生物标志物

• 批准号: 8210883
• 负责人: JAMES R EWING
• 金额: $ 30.73万
• 依托单位: HENRY FORD HEALTH SYSTEM
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2014-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8210883
• 关键词: Angiogenesis Inhibitors; Animal Model; Arsenic Trioxide; Biological Markers; Blood; Blood Vessels; Blood Volume; Blood flow; Brain; Brain Neoplasms; Cerebral Neoplasm; Cerebrum; Cilengitide; Clinic; Clinical; Combined Modality Therapy; Contrast Media; Data; Detection; Discrimination; Drug Kinetics; Event; Extracellular Space; Glioma; Grant; Human; Image; Implant; Institution; Magnetic Resonance; Magnetic Resonance Imaging; Malignant Glioma; Measures; Modeling; Monitor; Multivariate Analysis; New Approaches to Brain Tumor Therapy Consortium; Nude Rats; Operative Surgical Procedures; Patients; Phase II Clinical Trials; Phase III Clinical Trials; Physiology; Published Comment; Radiation therapy; Radiosurgery; Recording of previous events; Research; Series; Solutions; Stroke; Surrogate Markers; Techniques; Time; Tissues; Translating; Translational Research; Translations; U251; Work; cancer therapy; cell killing; chemotherapy; density; design; extracellular; heuristics; neoplastic cell; public health relevance; research study; response; treatment response; tumor; vascular bed

DESCRIPTION (provided by applicant): Malignant gliomas present great difficulties in treatment, with little change over the past 25 years in the median survival time of 12 months. Current treatment options include surgery, radiotherapy (RT), and chemotherapy. New therapies aimed at suppressing the formation of new vasculature (antiangiogenic treatments), or destroying formed tumor vasculature (vascular disrupting agents) show promise. This application will use magnetic resonance (MR) contrast agents (CAs) and MR detection to measure blood volume, the blood-to-brain transvascular transfer constant, the extravascular extracellular space, and the total extracellular space in cerebral tumors, and also to measure tumor blood flow using MR arterial spin tagging. These parameters present an important summary of the physiology of vasculature, both normal and tumorous. It is proposed to use these vascular parameters as MR biomarkers in animal models of cerebral gliomas. In a series of experiments, we will examine the change in MR-measured vascular parameters after antiangiogenic therapy, after vascular disrupting agent, and after RT, with all MR measures correlated with histopathological assessments of vascular and cellular density in the model tumors. After single-agent therapies are studied, combination therapies will be studied, and MRI vascular biomarkers will be examined as predictors of response as judged both by histopathological assessments and long-term survival. At the completion of these studies, the relation of MR-measured vascular parameters to cellular responses to single and combination therapies will be established, and the utility of MR-measured vascular parameters as predictors of long-term survival assessed. The MR-measured parameters can be translated to clinical use and evaluated as predictors of human tumor response to therapies. These studies represent a first step in a paradigm shift in cancer treatment delivery from a heuristic and formulaic approach to an individualized plan of image guided treatment and response monitoring. PUBLIC HEALTH RELEVANCE: The utility of quantitative MR-measured vascular parameters for predicting brain tumor response to promising anti-angiogenic agents and vascular disrupting agents applied singly or in combination with or without radiation therapy will be shown. The studies presented represent a first step in a paradigm shift in cancer treatment delivery from a one-solution-fits-all approach to an individualized plan of image guided treatment and response monitoring.

描述（由申请人提供）：恶性胶质瘤在治疗方面存在很大困难，在过去25年中，中位生存时间12个月几乎没有变化。目前的治疗方案包括手术、放疗（RT）和化疗。旨在抑制新血管形成（抗血管生成治疗）或破坏已形成的肿瘤血管（血管破坏剂）的新疗法显示出希望。该应用将使用磁共振（MR）造影剂（CA）和MR检测来测量脑肿瘤中的血容量、血-脑经血管转移常数、血管外细胞外间隙和总细胞外间隙，并使用MR动脉自旋标记来测量肿瘤血流量。这些参数是正常和肿瘤血管生理学的重要总结。建议将这些血管参数作为脑胶质瘤动物模型的MR生物标志物。在一系列的实验中，我们将检查MR测量的血管参数的变化后，抗血管生成治疗后，血管破坏剂后，和RT后，与所有的MR测量与模型肿瘤中的血管和细胞密度的组织病理学评估。在研究单药治疗后，将研究联合治疗，并检查MRI血管生物标志物作为通过组织病理学评估和长期生存期判断的缓解预测因子。在这些研究完成时，将建立MR测量的血管参数与对单药和联合治疗的细胞反应的关系，并评估MR测量的血管参数作为长期生存预测因子的效用。MR测量的参数可以转化为临床应用，并作为人类肿瘤对治疗反应的预测因子进行评价。这些研究代表了癌症治疗从启发式和公式化方法到图像引导治疗和反应监测的个性化计划的范式转变的第一步。 公共卫生关系：将显示定量MR测量的血管参数用于预测脑肿瘤对有前景的抗血管生成剂和血管破坏剂的反应的效用，所述抗血管生成剂和血管破坏剂单独或与或不与放射治疗组合应用。这些研究代表了癌症治疗从一种解决方案适合所有方法到图像引导治疗和反应监测的个性化计划的范式转变的第一步。