ISMRM 21st Annual Meeting & Exhibition ○ 20-26 April 2013 ○ Salt Lake City, Utah, USA
SCIENTIFIC SESSION
Tumor Therapy Response: Clinical & Preclinical Wednesday 24 April 2013
Room 355 EF | 13:30 - 15:30 | Moderators: | Nandita M. DeSouza, Tom W. J. Scheenen
13:30 | 0499. | Investigating Quantitative Imaging Biomarkers of Response to Cabozantinib in a VCaP Model of Prostate Bone Metastasis Timothy James Graham1, Gary Box2, Ruth Riisnaes2, Susana Miranda2, Gerhardt Attard2, Johann S. de Bono2, Suzanne A. Eccles2, Faith E. Davies2, and Simon P. Robinson1 1Division of Radiotherapy and Imaging, The Institute of Cancer Research, Sutton, Surrey, United Kingdom, 2Cancer Therapeutics Unit, The Institute of Cancer Research, Sutton, Surrey, United Kingdom With the development of more targeted therapeutics to treat malignant bone disease has come the associated challenge of developing more clinically relevant pre-clinical models, and identifying new non-invasive techniques capable of assessing the tumour phenotype and treatment response. To this end, a mouse model of castrate-resistant, prostate bone metastasis, propagated by direct intraosseous injection of cells, and its response to cabozantinib, has been investigated by quantitative imaging methods.
13:42 | 0500. | Diffusion-Weighted Magnetic Resonance Imaging of Response to PI3-Kinase/mTOR Inhibition Studied in Human Ovarian Cancer Xenografts Jana Cebulla1, Siver A. Moestue1, Else Marie Huuse1, Geir Bjørkøy2, Tone Frost Bathen1, and Ingrid Susann Gribbestad1 1Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway, 2Department of Technology, University College of Sør-Trøndelag (HiST), Trondheim, Norway The PI3-Kinase pathway is often upregulated in cancer cells and is therefore a promising target for anticancer therapy. This novel treatment strategy induces a need for biomarkers that can non-invasively and repeatedly assess therapy response. In this study we used diffusion weighted MRI to evaluate changes in the apparent diffusion coefficient (ADC) caused by PI3-kinase/mTOR inhibition in ovarian tumor xenografts. For responding tumors we found a significant increase in median ADC values and a decrease in kurtosis and skewness of ADC histograms, suggesting that these parameters are promising candidates for clinical biomarkers for PI3-Kinase/mTOR inhibition.
13:54 | 0501. | Dual PI3K/mTOR Inhibition Suppresses Tumor PO2 Within Viable Tumor Assessed by 19F-MRI and Multispectral Analysis Yunzhou Shi1, Jason Oeh2, Jeffrey Eastham-Anderson3, Sharon Yee2, David Finkle2, Franklin V. Peale3, Jed Ross1, Maj Hedehus1, Nicholas van Bruggen1, Rayna Venook2, Sarajane Ross2, Deepak Sampath2, and Richard A. D. Carano4 1Biomedical Imaging, Genentech Inc.(Roche Group), South San Francisco, CA, United States, 2Translational Oncology, Genentech Inc.(Roche Group), South San Francisco, CA, United States,3Pathology, Genentech Inc.(Roche Group), South San Francisco, CA, United States, 4Biomedical Imaging, Genentech, South San Francisco, CA, United States The effect of a novel dual PI3K/mTOR inhibitor on tumor oxygen level was studied using a novel approach that combines 19F-MRI T1 mapping with diffusion-based multispectral K-means clustering. The current study aims to elucidate the role of PI3K/mTOR signaling on oxygen level in viable tumor. An anti-angiogenic agent, B20.4.1.1, was employed as a positive control for its known anti-vascular effects. We were able to monitor pO2 for 72h without fluorine signal loss. The current results advocate for the use of the multispectral 19F-MRI technique as a tool to better understand the mode of action of therapies that alter tumor’s microenvironment.
14:06 | 0502. | Using MRI to Track SPIO-Labeled Effector and Regulatory Immune Cells in a Cancer Model Kimberly Brewer1,2, Christa Davis3, Iulia Dude3, Genevieve Weir1, Olivia Stanley3, Mohan Karkada1, Marc Mansour1, and Chris Bowen2,3 1Immunovaccine Inc., Halifax, NS, Canada, 2Biomedical Engineering, Dalhousie University, Halifax, NS, Canada, 3Institute for Biodiagnostics (Atlantic), Halifax, NS, Canada A growing area of interest in cancer research is the behaviour of regulatory cells such as myeloid derived suppressor cells and regulatory T cells. These cells suppress both inherent and induced immune responses (i.e. via treatments such as immunotherapies) resulting in the underperformance of many anti-cancer treatments. Our current work used MRI to investigate the migration patterns of three types of SPIO-labeled immune cells in a mouse tumor model. The objectives of this study were to demonstrate reliable homing of regulatory and effector cells to tumors and lymph nodes, and observe changes in these patterns in response to cancer immunotherapy.
14:18 | 0503. | Amide Proton Transfer MRI Evaluation of Bladder Cancer Neoadjuvant Chemotherapy Guang Jia1, Huyen Thanh Nguyen1, Kamal S. Pohar2, Amir Mortazavi3, Zarine K. Shah1, Lai Wei4, and Michael V. Knopp1 1Department of Radiology, The Ohio State University, Columbus, OH, United States, 2Department of Urology, The Ohio State University, Columbus, OH, United States, 3Department of Medical Oncology, The Ohio State University, Columbus, OH, United States, 4Center for Biostatistics, The Ohio State University, Columbus, OH, United States This study was conducted to evaluate the role of APT-MRI in bladder cancer neoadjuvant chemotherapy response assessment.
14:30 | 0504. | Early Prediction of Breast Cancer Therapeutic Response and Evaluation of Residual Disease Using Quantitative DCE-MRI Alina Tudorica1, Karen Y. Oh1, Stephen Y.-C. Chui1, Nicole Roy1, Megan L. Troxell1, Yiyi Chen1, Arpana Naik1, Ariel Lopez-Chavez1, Megan L. Holtorf1, Aneela Afzal1, Mohan L. Jayatilake1, Zunqiu Chen1, Charles S. Springer, Jr.1, Xin Li1, and Wei Huang1 1Oregon Health & Science University, Portland, OR, United States Eleven consecutive women with locally advanced breast cancer underwent research DCE-MRI before, after one cycle, at midpoint, and after completion of neoadjuvant chemotherapy. MRI data were analyzed using the Standard and Shutter-Speed models (SM and SSM). % changes in tumor Ktrans (SM and SSM), kep (SM and SSM), and tau_i (SSM only), as well as the absolute values of Ktrans (SSM) and kep (SM and SSM) after one cycle of therapy completely discriminated 3 responders from 8 non-responders. The tau_i value after therapy correlated significantly with residual disease burden.
14:42 | 0505. | Characterizing Response in Head and Neck Cancer with Cluster Analysis of Multi-Parametric MRI Data Marco Borri1, Maria A. Schmidt1, Ceri Powell2, Dow-Mu Koh1,3, Angela Riddell3, Kate Newbold2, and Martin O. Leach1 1CR-UK and EPSRC Cancer Imaging Centre, Institute of Cancer Research and Royal Marsden, Sutton, Surrey, United Kingdom, 2Head and Neck Dept., The Royal Marsden NHS Foundation Trust, Sutton, Surrey, United Kingdom, 3Radiology Dept., The Royal Marsden NHS Foundation Trust, Sutton, Surrey, United Kingdom One of the main challenges in the management of head and neck squamous cell carcinomas (HNSCC) is the inability to predict outcome because of tumour heterogeneity. We propose a method, based on cluster analysis, to robustly partition head and neck lesions in sub-regions using complementary functional information from DCE and DWI. This approach was able to spatially describe functional heterogeneity in a cohort of patients with histologically proven HNSCC undergoing radical chemoradiotherapy, and allowed identification of sub-regions of the tumours which were affected differently by treatment and their characterization with functional parameters.
14:54 | 0506. | Comparison of Arterial Spin Labelling and R2* as Predictive Response Biomarkers for Vascular Targeting Agents in Liver Metastases Sean Peter Johnson 1, Rajiv Ramasawmy2, Adrienne E. Campbell-Washburn2, Mathew Robson1, Jack Wells2, Vineeth Rajkumar1, Simon Walker-Samuel2, Mark F. Lythgoe2, and Rosamund Barbara Pedley1 1Cancer Institute, University College London, London, Greater London, United Kingdom, 2Centre for Advanced Biomedical Imaging, University College London, London, Greater London, United Kingdom We present data comparing the ability of arterial spin labelling (ASL) perfusion measurements and R2* to assess response to vascular disrupting agent therapy in a mouse liver metastasis model. A significant increase in R2* (p<0.01, n=12) and a significant decrease in perfusion (p<0.01, n=18) were measured. Baseline perfusion was significantly correlated with the subsequent change in perfusion at 90 minutes following therapy, whilst baseline R2* values did not show a relationship with response. No significant correlation was found between perfusion and R2* post-therapy changes.
15:06 | 0507. | Evaluate the Efficacy of Intravoxel Incoherent Motion Imaging in Predicting Treatment Outcome in Patients with Head and Neck Cancer Yonggang Lu1, Jacobus F.A. Jansen2, Hilda E. Stambuk3, Gaorav Gupta4, Nancy Lee4, Mithat Gonen5, Andre E. Moreira6, Snehal G. Patel7, Joseph O. Deasy1, Jatin P. Shah7, and Amita Shukla-Dave1,3 1Medical Physics Department, Memorial Sloan-kettering Cancer Center, New York, NY, United States, 2Department of Radiology, Maastricht University, Maastricht, Netherlands, 3Radiology Department, Memorial Sloan-kettering Cancer Center, New York, NY, United States, 4Radiation Oncology Department, Memorial Sloan-kettering Cancer Center, New York, NY, United States,5Biostatistics Department, Memorial Sloan-kettering Cancer Center, New York, NY, United States, 6Pathology Department, Memorial Sloan-kettering Cancer Center, New York, NY, United States,7Surgery Department, Memorial Sloan-kettering Cancer Center, New York, NY, United States The purpose of this study was to evaluate the efficacy of intravoxel incoherent motion imaging in predicting treatment outcome in patients with head and neck cancer. Sixteen patients with both primary tumor and metastatic nodes were enrolled. The results demonstrated that measures of std(D) in both primary tumors and metastatic nodes were found to be predictors of outcome (progression free (PFS) and overall survival (OS)), but std(D) from primary tumors had more sensitivity in predicting PFS than from metastatic nodes. After appropriate validation in larger patient population, these findings may be useful in optimizing treatment planning and improving patient care.
15:18 | 0508. | Diffusion Weighted Imaging Detects Significant Cohort Responses After Seven Days of Treatment with Cediranib in a Phase I Clinical Trial Setting Matthew R. Orton1, Christina Messiou2, David John Collins1, Veronica A. Morgan2, Dionysis Papadatospastos3, Andre Brunetto3, Jooern Ang3, Helen Mann4, Jean Tessier4, Helen Young4, Stan Kaye3, Johann S. de Bono3, Martin O. Leach1, and Nandita M. De Souza1 1CR-UK and EPSRC Cancer Imaging Centre, Institute of Cancer Research, Sutton, Surrey, United Kingdom, 2Radiology Department, Royal Marsden NHS Foundation Trust, Sutton, Surrey, United Kingdom, 3Department of Medicine, Royal Marsden NHS Foundation Trust, Sutton, Surrey, United Kingdom, 4AstraZeneca, Macclesfield, Cheshire, United Kingdom Although DWI measures have previously been reported demonstrating changes with anti-angiogenic agents at 28 days, the response at 7 days has not been widely reported as it is assumed that DWI is insensitive to perfusion changes with an antiangiogenic agent in such a short time-frame. The purpose of this study was to assess changes in DWI derived measures at both 7 and 28 days for a cohort of patients treated with Cediranib. Significant cohort changes are seen at 7 days and these can be detected using a number of diffusion attenuation models, in particular with the stretched-exponential model.