PET-MRI for Assessing Treatment Response in Breast Cancer Clinical Trials

PET-MRI 用于评估乳腺癌临床试验中的治疗反应

• 批准号: 8657857
• 负责人: Vandana Abramson
• 金额: $ 42.41万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8657857
• 关键词: Address; Algorithmic Software; Angiogenesis Inhibition; Antineoplastic Agents; Apoptosis; Architecture; Basic Science; Biological; Biological Markers; Blood Vessels; Breast; Breast Cancer Treatment; Carboplatin; Caring; Cell Proliferation; Cellularity; Cisplatin; Clinical; Clinical Data; Clinical Sciences; Clinical Trials; Communities; Data; Data Analyses; Development; Diffusion Magnetic Resonance Imaging; ERBB2 gene; Goals; Healthcare; Image; Imaging technology; Magnetic Resonance Imaging; Mammary Neoplasms; Measurement; Measures; Methods; Metric; Molecular; Neoadjuvant Therapy; Operative Surgical Procedures; Paclitaxel; Pathology; Patients; Physiological; Positron-Emission Tomography; Principal Investigator; Protocols documentation; Radiology Specialty; Reporting; SDZ RAD; Science; Staging; The Vanderbilt-Ingram Cancer Center at the Vanderbilt University; Time; Tissues; Translations; Vorinostat; Weight; angiogenesis; antiangiogenesis therapy; clinical decision-making; data acquisition; glucose metabolism; inhibitor/antagonist; mTOR Inhibitor; malignant breast neoplasm; non-invasive imaging; novel; oncology; outcome forecast; phase 2 study; response; treatment response; tumor; user-friendly

DESCRIPTION (provided by applicant): We propose to develop integrated high field (3T) magnetic resonance imaging (MRI) and positron emission tomography (PET) methods for assessing the effects of molecularly targeted anti-angiogenesis and cytoxic treatments in breast cancer clinical trials. Our goal is to provide the breast cancer community with practical data acquisition and analysis protocols that facilitate the translation of advanced imaging technologies into patient management and clinical trials. Dynamic contrast enhanced MRI (DCE-MRI) and diffusion weighted MRI (DW-MRI) can report on vascular status, tissue volume fractions, and cellularity, while fluorodeoxythymidine PET (FLT-PET) can report on cell proliferation. We propose to combine these MRI and PET data to provide anatomical, physiological, and molecular assessments of the response of breast tumors to novel anti-angiogenic and cytoxic treatments in clinical trials. To accomplish these goals we will pursue the following specific aims: 1. We will develop high field breast MRI protocols that measure tissue cellularity and vascularity. We will then develop methods for the rigorous registration of these MRI measures with quantitative PET characterization of cell proliferation. We will develop the algorithms and software architecture necessary for synthesizing the imaging data with (traditional) clinical data to assisting in clinical decision making. 2. In an ongoing Phase II study we will employ DCE-MRI, DW-MRI, and FLT-PET to assess the degree of tumor response after one and two cycles of Carboplatin and nab-Paclitaxel with or without Vorinostat in HER2-negative primary operable breast cancer. 3. In our planned Phase II study we will employ DCE-MRI, DW-MRI, and FLT-PET to assess the degree of tumor response after one and two cycles of neoadjuvant cisplatin, paclitaxel and the TOI inhibitor everolimus in patients with triple negative breast tumors. As the anti-cancer agents employed in these clinical trials are implicated in apoptosis and/or inhibition of cellular proliferation and/or inhibition of angiogenesis, we hypothesize that changes in metrics of cellular proliferation and vascularity, when merged with traditional clinical biomarkers, will provide significantly more accurate predictions on patient response than traditional methods of tumor response including RECIST. RELEVANCE: We propose to develop integrated magnetic resonance imaging (MRI) and positron emission tomography (PET) methods for assessing the effects of molecularly targeted treatments in breast cancer clinical trials. We hypothesize that the synthesis of imaging metrics reporting on vascularity, cellularity, and cell proliferation will provide predictive measurements of tumor response to treatment in appropriately selected clinical trials. Our goal is to provide the breast cancer community with practical data acquisition and analysis protocols that facilitate the translation of advanced imaging technologies into patient management and clinical trials.

描述（由申请人提供）：我们建议开发集成高场（3 T）磁共振成像（MRI）和正电子发射断层扫描（PET）方法，用于评估乳腺癌临床试验中分子靶向抗血管生成和细胞毒性治疗的效果。我们的目标是为乳腺癌社区提供实用的数据采集和分析协议，促进先进的成像技术转化为患者管理和临床试验。动态对比增强MRI（DCE-MRI）和扩散加权MRI（DW-MRI）可以报告血管状态、组织体积分数和细胞结构，而氟脱氧胸苷PET（FLT-PET）可以报告细胞增殖。我们建议将这些MRI和PET数据联合收割机，在临床试验中提供乳腺肿瘤对新型抗血管生成和细胞毒性治疗反应的解剖学、生理学和分子学评估。为了实现这些目标，我们将追求以下具体目标：1。我们将开发高场乳腺MRI协议，测量组织细胞和血管。然后，我们将开发这些MRI测量与定量PET表征细胞增殖的严格注册的方法。我们将开发合成成像数据与（传统）临床数据所需的算法和软件架构，以协助临床决策。 2.在一项正在进行的II期研究中，我们将使用DCE-MRI、DW-MRI和FLT-PET评估在HER 2阴性原发性可手术乳腺癌中使用或不使用伏立诺他的情况下使用卡铂和nab-Paclitazone 1个和2个周期后的肿瘤缓解程度。 3.在我们计划的II期研究中，我们将使用DCE-MRI、DW-MRI和FLT-PET来评估三阴性乳腺肿瘤患者在新辅助顺铂、紫杉醇和TOI抑制剂依维莫司治疗一个和两个周期后的肿瘤缓解程度。由于这些临床试验中使用的抗癌药物涉及细胞凋亡和/或细胞增殖抑制和/或血管生成抑制，我们假设细胞增殖和血管分布指标的变化与传统的临床生物标志物结合时，将比传统的肿瘤缓解方法（包括RECIST）提供更准确的患者缓解预测。 相关性：我们建议开发集成的磁共振成像（MRI）和正电子发射断层扫描（PET）的方法来评估乳腺癌临床试验中的分子靶向治疗的效果。我们假设，在适当选择的临床试验中，报告血管分布、细胞构成和细胞增殖的成像指标的综合将提供肿瘤对治疗反应的预测性测量。我们的目标是为乳腺癌社区提供实用的数据采集和分析协议，促进先进的成像技术转化为患者管理和临床试验。