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

描述（由申请人提供）：我们建议开发综合高场（3T）磁共振成像（MRI）和正电子发射断层扫描（PET）方法，以评估分子靶向抗血管生成和细胞毒性治疗在乳腺癌临床试验中的效果。我们的目标是为乳腺癌社区提供实用的数据采集和分析方案，促进将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，而氟脱氧胸腺嘧啶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性治疗反应的解剖、生理和分子评估。为实现这些目标，我们将努力实现以下具体目标：我们将开发高场乳房MRI方案来测量组织细胞和血管。然后，我们将开发方法，严格登记这些MRI措施与定量PET表征细胞增殖。我们将开发合成影像数据与（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，我们将采用DCE-MRI、DW-MRI和FLT-PET来评估在her2阴性的原发性可手术乳腺癌患者中，卡铂和nab-紫杉醇联合或不联合Vorinostat治疗1和2个周期后的肿瘤反应程度。3. 在我们计划的II期研究中，我们将采用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抑制剂依维莫司一个和两个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/或细胞增殖抑制和/或血管生成抑制有关，我们假设，当与传统的临床生物标志物结合时，细胞增殖和血管的变化指标将比传统的肿瘤反应方法（包括RECIST）提供更准确的患者反应预测。

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.