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

描述(申请人提供)：我们建议开发集成的高场(3T)磁共振成像(MRI)和正电子发射断层扫描(PET)方法，用于在乳腺癌临床试验中评估分子靶向抗血管生成和细胞毒治疗的效果。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，促进将先进的成像技术转化为患者管理和临床试验。动态增强MRI(DCE-MRI)和弥散加权MRI(DW-MRI)可以报告血管状态、组织体积分数和细胞密度，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数据结合起来，在临床试验中提供乳腺肿瘤对新型抗血管生成和细胞毒治疗的反应的解剖学、生理学和分子评估。为了实现这些目标，我们将追求以下具体目标：1.我们将开发测量组织细胞密度和血管密度的高场强乳腺MRI方案。然后，我们将开发方法，将这些MRI测量与细胞增殖的定量PET表征严格配准。我们将开发将成像数据与(传统)临床数据合成所需的算法和软件架构，以帮助临床决策。2.在正在进行的第二阶段研究中，我们将使用DCE-MRI、DW-MRI和Flt-PET来评估在HER2阴性的初次可手术乳腺癌患者接受卡铂和NAB-紫杉醇加或不加Vorinostat一周期和两周期后的肿瘤反应程度。3.在我们计划的第二阶段研究中，我们将使用DCE-MRI、DW-MRI和Flt-PET来评估三重阴性乳腺肿瘤患者接受新辅助顺铂、紫杉醇和TOI抑制剂依维莫司治疗一周期和两周期后的肿瘤反应程度。由于这些临床试验中使用的抗癌药物与细胞凋亡和/或抑制细胞增殖和/或抑制血管生成有关，我们假设，当细胞增殖和血管指标的变化与传统的临床生物标记物结合时，将比包括RECIST在内的传统肿瘤反应方法提供显著更准确的患者反应预测。 相关性：我们建议开发综合磁共振成像(MRI)和正电子发射断层扫描(PET)方法来评估乳腺癌临床试验中分子靶向治疗的效果。我们假设，在适当选择的临床试验中，报告血管密度、细胞密度和细胞增殖的综合成像指标将提供对肿瘤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，促进将先进的成像技术转化为患者管理和临床试验。

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.