DIFFUSION MRI AS BIOMARKER FOR THERAPY RESPONSE IN BREAST CANCER METASTASES

扩散 MRI 作为乳腺癌转移治疗反应的生物标志物

• 批准号: 7808843
• 负责人: Alison T. STOPECK
• 金额: $ 35.3万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-14 至 2013-05-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7808843
• 关键词: 3-Dimensional; Anatomy; Biochemical; Biological Markers; Brain; Cancer Patient; Caring; Chemotherapy-Oncologic Procedure; Clinical; Clinical Data; Clinical Trials Design; Cranial Irradiation; Cytotoxic Chemotherapy; Cytotoxic agent; Data; Data Set; Development; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Echo-Planar Imaging; Goals; Hormonal; Image; Image Analysis; Investigational Therapies; Knowledge; Lesion; Liver; Magnetic Resonance Imaging; Maps; Measures; Metastatic Lesion; Metastatic Neoplasm to the Bone; Metastatic Neoplasm to the Liver; Metastatic malignant neoplasm to brain; Methods; Monitor; Morbidity - disease rate; Morphologic artifacts; Motion; Multicenter Trials; Neoplasm Metastasis; Oncologist; Outcome; Patient Care; Patient Monitoring; Patients; Predisposition; Protocols documentation; Radial; Reaction Time; Recurrence; Relative (related person); Reproducibility; Research; Resolution; Scanning; Site; Support Groups; Taxane Compound; Techniques; Testing; Texture; Therapeutic; Therapy Clinical Trials; Time; Tissues; Validation; Water; Weight; Work; arm; base; bone; cancer therapy; chemotherapy; clinical practice; cytotoxic; experience; follow-up; hormone therapy; human data; image registration; improved; malignant breast neoplasm; pre-clinical; response; routine care; statistics; taxane; tool; tumor

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.

描述（由申请人提供）：21世纪对肿瘤学家的挑战将是患者护理的个性化。在某些癌症中，治疗决策已经基于患者的生化指标以及这些指标对治疗的反应。显然，开发非侵入性和强大的方法来监测治疗反应将有助于对个体化癌症治疗的整体护理。如果开发了这种方法，则可以在成功的疗法上继续使用患者，并因证明无效的疗法而改变。我们假设扩散MRI测量了组织水的明显扩散系数（ADC），具有对有效癌症化学疗法的非侵入性标记的巨大潜力。大量的临床前数据表明，成功的抗癌化疗后，肿瘤水的ADC升高。基于这些数据的强度，已经提出了ADC的变化作为定量生物标志物，以在临床环境中响应。来自一些研究小组的初步人类数据支持以下假设：ADC的早期增加可以预测最终的临床益处。我们的小组通过专注于转移性乳腺癌为这项工作做出了贡献。我们之所以专注于这种疾病的设定，主要是因为有治疗选择，因此患者可以从反应知识（或不反应）中受益。在初步数据中，我们已经观察到从肝癌患者的肝脏和骨骼的常见转移性部位的扩散MR图像中ADC中与治疗相关的变化。该提案的目的是扩大这项工作，以确定ADC的早期变化是否可以定量预示肝脏（AIM 1），骨骼（AIM 2）和大脑（AIM 3）转移的临床反应。第四个目标集中在开发更复杂的图像分析工具上，目的是从DWMRI数据集中提取最多信息。当前方案将使用已知响应率的批准疗法，以验证扩散MRI作为响应生物标志物。如果从这项研究中有理由，将在一项多中心试验中进行进一步的验证，旨在测试扩散MRI是否对监测常规临床实践中的治疗反应以及实验疗法的试验。

项目成果

A maximum-likelihood method to estimate a single ADC value of lesions using diffusion MRI.

• DOI: 10.1002/mrm.26072
• 发表时间: 2016-12
• 期刊: Magnetic resonance in medicine
• 影响因子: 3.3
• 作者: Jha AK;Rodríguez JJ;Stopeck AT
• 通讯作者: Stopeck AT

Diffusion MRI with Semi-Automated Segmentation Can Serve as a Restricted Predictive Biomarker of the Therapeutic Response of Liver Metastasis.

具有半自动分割功能的扩散 MRI 可以作为肝转移治疗反应的限制性预测生物标志物。

• DOI: 10.1016/j.mri.2015.08.006
• 发表时间: 2015
• 期刊: Magnetic resonance imaging
• 影响因子: 2.5
• 作者: Stephen,RenuM;Jha,AbhinavK;Roe,DeniseJ;Trouard,TheodoreP;Galons,Jean-Philippe;Kupinski,MatthewA;Frey,Georgette;Cui,Haiyan;Squire,Scott;Pagel,MarkD;Rodriguez,JeffreyJ;Gillies,RobertJ;Stopeck,AlisonT
• 通讯作者: Stopeck,AlisonT

A Clustering Algorithm for Liver Lesion Segmentation of Diffusion-Weighted MR Images.

• DOI: 10.1109/ssiai.2010.5483911
• 发表时间: 2010-05-23
• 期刊: Proceedings. IEEE Southwest Symposium on Image Analysis and Interpretation
• 作者: Jha AK;Rodríguez JJ;Stephen RM;Stopeck AT
• 通讯作者: Stopeck AT

Evaluating segmentation algorithms for diffusion-weighted MR images: a task-based approach.

评估扩散加权 MR 图像的分割算法：基于任务的方法。

• DOI: 10.1117/12.845515
• 发表时间: 2010
• 期刊: Proceedings of SPIE--the International Society for Optical Engineering
• 作者: Jha,AbhinavK;Kupinski,MatthewA;Rodríguez,JeffreyJ;Stephen,RenuM;Stopeck,AlisonT
• 通讯作者: Stopeck,AlisonT