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Vanderbilt University

PET-MRI for Assessing Treatment Response in Breast Cancer Clinical Trials
Thomas E. Yankeelov. Ph.D.
THOMAS.YANKEELOV@VANDERBILT.EDU
Vanderbilt University
Grant Number: U01 CA142565

Vanderbilt University has developed an interdisciplinary group of scientists, supported by the Quantitative Imaging Network 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. The 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 fluorodeoxythymadine PET (FLT-PET) can report on cell proliferation. The investigators 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 they will pursue the following specific aims: 1. Develop high field breast MRI protocols that measure tissue cellularity and vascularity. They will then develop methods for the rigorous registration of these MRI measures with quantitative PET characterization of cell proliferation. They will develop the algorithms and software architecture necessary for synthesizing the imaging data with (traditional) clinical data to assisting in clinical decision making. In an ongoing Phase II study they 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. In the planned Phase II study they 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, they 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.

The goal of the proposed research is 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. The investigators 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. The 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.

The applicants proposed to address the research issues with the following aims:

Aim 1. (Developmental) The investigators will further develop and optimize high field breast DW-MRI and DCE-MRI protocols that measure tissue cellularity and vascularity which significantly outperform analogous 1.5T studies and which are appropriate for routine clinical use. They will then implement methods for the rigorous registration of these MRI measures with quantitative PET characterization of glucose metabolism or cell proliferation.
Aim 2. (Clinical Trial I) In an ongoing Phase II study (VICC BRE0869) they will employ DCE-MRI, DW-MRI, and FDG-PET to assess tumor response after one and two cycles of Carbopiatin and nab-Paclitaxel with or without Vorinostat in HER2-negafive stage II and III primary operable breast cancer.
Aim 3. (Clinical Trial II) In a planned Phase II study (VICC BRE0904) they will employ DCE-MRI, DW-MRI, and FLT-PET to assess tumor response after one and two cycles of neoadjuvant cisplatin and paclitaxel with or without the mTOR inhibitor everolimus in patients with triple-negative stage II and III breast cancers.