DIFFUSION MRI AS BIOMARKER FOR THERAPY RESPONSE IN BREAST CANCER METASTASES

描述(由申请人提供)：21世纪肿瘤学家面临的挑战将是患者护理的个性化。在一些癌症中，治疗决定是基于患者提出时的生化指标以及这些指标对治疗的反应。显然，发展非侵入性和可靠的方法来监测治疗反应将有助于对癌症个体化治疗的整体护理。如果开发出这样的方法，患者可以继续进行成功的治疗，并从被证明无效的治疗中改变。我们推测，磁共振扩散成像测量组织水的表观扩散系数(ADC)，有很大的潜力成为有效的癌症化疗的非侵入性标记物。大量的临床前数据表明，抗癌化疗成功后，肿瘤水的ADC值升高。根据这些数据的强度，ADC的变化已被建议作为临床环境下反应的定量生物标记物。来自几个研究小组的初步人类数据支持这样的假设，即ADC的早期增加可以预测最终的临床益处。我们小组通过专注于转移性乳腺癌为这一努力做出了贡献。我们之所以关注这一疾病背景，主要是因为有治疗选择，因此，患者可以从应答(或无应答)知识中受益。在初步数据中，我们从乳腺癌患者常见的肝脏和骨转移部位的扩散磁共振图像中观察到了与治疗相关的ADC变化。这项建议的目的是扩展这项工作，以确定ADC的早期变化是否可以定量预测乳腺癌肝(AIM 1)、骨(AIM 2)和脑(AIM 3)转移的临床反应。第四个目标是开发更复杂的图像分析工具，目标是从DWMRI数据集中提取最多的信息。目前的方案将使用已批准的具有已知应答率的疗法，以验证弥散磁共振成像作为反应生物标记物的有效性。如果这项研究证明了这一点，将在一项多中心试验中进行进一步的验证，该试验旨在测试扩散磁共振成像在常规临床实践和实验疗法试验中是否有助于监测治疗反应。

DESCRIPTION (provided by applicant): A challenge to oncologists in the 21st century will be the individualization of patient care. Already in some cancers, treatment decisions are based on patients' biochemical indicators at presentation and the response of these indicators to therapy. Clearly, the development of non-invasive and robust methods to monitor therapeutic response would be helpful to the overall care of individualizing cancer treatment. If such methods were developed, patients could be continued on successful therapies and changed from therapies that are proving ineffective. We hypothesize that diffusion MRI, which measures the apparent diffusion coefficient (ADC) of tissue water, has great potential to be a non-invasive marker for effective cancer chemotherapy. A significant amount of pre-clinical data indicates that the ADC of tumor water becomes elevated after successful anti-cancer chemotherapy. Based on the strength of these data, changes in ADC have been proposed as a quantitative biomarker for response in a clinical setting. Preliminary human data from a few research groups supports the hypothesis that early increases in ADC can predict ultimate clinical benefit. Our group has contributed to this endeavor by focusing on metastatic breast cancer. We have focused on this disease setting primarily because there are therapeutic choices, and hence, patients could benefit from knowledge of response (or non response). In preliminary data, we have observed therapy related changes in ADC in diffusion MR images from the common metastatic sites of liver and bone from breast cancer patients. The purpose of this proposal is to expand on this work to determine if early changes in the ADC can quantitatively presage clinical response in liver (Aim 1), bone (Aim 2) and brain (Aim 3) metastases of breast cancer. A fourth aim is focused on developing more sophisticated image analysis tools with the goal of extracting the most information from DWMRI datasets. The current protocol will use approved therapies with known response rates in order to validate diffusion MRI as a response biomarker. If justified from this study, further validation will be pursued in a multicenter trial designed to test if diffusion MRI will be useful to monitor therapeutic responses in routine clinical practice as well as in trials of experimental therapies.