Tumor Therapy Response: Preclinical & Clinical
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Monday 7 May 2012
Room 210-211  10:45 - 12:45 Moderators: Kristine Glunde, Anwar R. Padhani

10:45 0036.   
Measuring lymph node swelling using MRI to act as a biomarker for tumour suppression
Kim Brewer1,2, Drew DeBay3, Kerry Lake3, Iulia Dude3,4, Genevieve Weir1, Marc Mansour1, and Chris Bowen2,3
1Immunovaccine Inc., Halifax, NS, Canada, 2School of Biomedical Engineering, Dalhousie University, Halifax, NS, Canada, 3Institute for Biodiagnostics (Atlantic), National Research Council of Canada, Halifax, NS, Canada, 4Physics, University of Waterloo, Waterloo, ON, Canada

Immunotherapies are aimed at potentiating the body’s immune response. DepoVaxTM is an immunotherapy vaccine that encapsulates the tumor-associated antigens in liposomes, which are then suspended in oil. The oil acts as an adjuvant, which improves the potency of the peptides and aids in eliciting a strong immune response. This work investigated whether an increase in the draining lymph node (LN) volume (right inguinal LN) could be used as a biomarker for successful vaccination (i.e. successful tumor suppression). This was done by performing longitudinal LN volumetry using MRI to evaluate changes using receiver operating characteristic (ROC) curves.

10:57 0037.   
Chronic and acute anti-angiogenic treatment effects detected by arterial spin labeling in mouse tumor
Reshmi Rajendran1, Mei Yee Tang1, Huang Wei1, Jie Ming Liang1, Stephanie Choo1, Torsten Reese2, Hannes Hentze2, Susan van Boxtel2, Brian Henry2, and Kai Hsiang Chuang1
1Laboratory of Molecular Imaging, Singapore Bioimaging Consortium, Singapore, Singapore, 2Merck Sharp and Dohme, Singapore

We applied optimized Flow-sensitive Alternating Inversion Recovery (FAIR) ASL to non-invasively quantify tumor perfusion in a mouse xenograft model, in which acute (24-hour) and chronic (43-day) treatment effects of the VEGF inhibitor (Avastin®) was investigated. Our data indicate that significant reduction in tumor perfusion was seen after acute dosing (p<0.05 vs. the control group), suggesting FAIR ASL perfusion could be used as an early biomarker for treatment response. Similarly, the chronic treatment of Avastin also led to a decrease in tumor size and perfusion; however, the drug effect varied significantly among the animals, possibly due to the heterogeneity of tumor progression.

11:09 0038.   
Mapping water exchange in rat tumour xenografts: using multiple flip angles during late-uptake stages following contrast agent injection
Colleen Bailey1,2, Firas Moosvi1,2, and Greg J Stanisz1,2
1Medical Biophysics, University of Toronto, Toronto, ON, Canada, 2Imaging Research, Sunnybrook Health Sciences Centre, Toronto, ON, Canada

Intra-to-extracellular water exchange has been shown to increase during apoptotic cell death in vitro. To map exchange in vivo, four flip angles were used during the late near-constant stages of uptake following three separate injections of Gd-DTPA-BMA in rat tumour xenografts. High extracellular water fraction corresponded to low cellularity on H&E. Regions of low water exchange were negative on TUNEL staining, while regions of high water exchange were positive, indicating apoptosis. High water exchange was observed even in cases where cells had not cleared and water fraction did not yet show a change.

11:21 0039.   
A New Biomarker for the Assessment of Early Tumor Response to Chemotherapy Using MR Elastography (MRE)
Kay Pelletier1, Kiaran McGee2, Jun Chen2, Kevin Glaser2, Stephen Ansell3, and Richard Ehman2
1Mayo Graduate School, Mayo Clinic, Rochester, Minnesota, United States, 2Radiology, Mayo Clinic, Rochester, MN, United States, 3Hematology, Mayo Clinic, Rochester, MN, United States

It is appreciated that a significant delay exists from the initiation of chemotherapy to the detection of a response as assessed by changes in tumor volume. In vivo serial measurements in a non-Hodgkin’s lymphoma mouse tumor model have demonstrated that tumor stiffness measured with MR Elastography (MRE) decreases following chemotherapy administration in comparison to saline-treated (placebo) tumors. This difference is statistically significant 48 hours following drug administration. These data suggest that tumor stiffness may be an earlier and more sensitive biomarker of therapeutic response than the current imaging-based methods such as FDG-PET, MRI and CT

11:33 0040.   
Characterisation of a novel orthotopic mouse model of multiple myeloma and therapeutic response by quantitative MRI
Timothy J Graham1, Rosemary A Fryer2, Yann Jamin1, Emma M Smith2, Simon Walker-Samuel3, Faith E Davies2, and Simon P Robinson1
1Cancer Research UK & EPSRC Cancer Imaging Centre, The Institute of Cancer Research, London, Surrey, United Kingdom, 2Haemato-Oncology Research Unit, Division of Molecular Pathology, The Institute of Cancer Research, London, Surrey, United Kingdom, 3Centre for Advanced Biomedical Imaging, University College London, London, 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 novel mouse model of multiple myeloma, propagated by direct intraosseous injection of cells, has been investigated by quantitative MRI. Tumour growth was localised to the skeleton, and assessed using high-resolution T2-weighted and diffusion-weighted imaging. Response to Bortezomib and Tosedostat was also assessed. Bioluminescence imaging , weekly Igλ serum levels, histology and flow cytometry provided qualification of the MRI data.

11:45 0041.   
Parameterizing the Logistic Model of Tumor Growth by DW-MRI and DCE-MRI to Predict Breast Tumor Cellularity During Neoadjuvant Chemotherapy
Nkiruka C Atuegwu1,2, Lori R Arlinghaus1,2, Xia Li1,2, E Brian Welch1,2, A Bapsi Chakravarthy3, and Thomas E Yankeelov1,2
1Institute of Imaging Science, Vanderbilt University, Nashville, TN, United States, 2Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, United States, 3Radiation Oncology, Vanderbilt University, Nashville, TN, United States

Sequential diffusion weighted MRI (DW-MRI) and dynamic contrast enhanced MRI (DCE-MRI) data were acquired on twelve patients with localized invasive breast cancer undergoing neoadjuvant chemotherapy. The DW-MRI and DCE-MRI data were incorporated into the logistic model of tumor growth to extract the proliferation rates of the tumors and this was then used to calculate the number of cells at the conclusion of therapy. The simulated and the experimentally estimated number of cells at the conclusion of therapy were then compared.

11:57 0042.   Multi-parametric approach for the assessment of tumor response to chemotherapy in locally advanced breast cancer (LABC) patients: Sequential MRI, DWI and in-vivo MRS study
Naranamangalam Raghunathan Jagannathan1, Rani G Sah1, Uma Sharma1, Rajinder Parshad2, and Vurthaluru Seenu2
1Department of NMR & MRI Facility, All India Institute of Medical Sciences, New Delhi, Delhi, India, 2Department of Surgery, All India Institute of Medical Sciences, New Delhi, Delhi, India

Sequential MRI and MRS before therapy and after I, II and neo-adjuvant chemotherapy (NACT) was carried out in 41 breast cancer patients to evaluate the potential of total choline (tCho), ADC and tumor volume to predict tumor response. Our data revealed significant decrease in tCho and ADC after I NACT compared to pre-therapy in responders compared to non-responders. Percentage reduction in tCho was significantly higher compared to ADC and volume in responders after I NACT, which demonstrated early change in metabolic activity compared to structural changes. The combined specificity of all the 3 parameters was higher than the individual parameter.

12:09 0043.   Transcatheter Intraarterial Perfusion MRI is an Intra-procedural Imaging Biomarker to Predict Survival during Chemoembolization of Hepatocellular Carcinoma
Dingxin Wang1,2, Ron Gaba3, Brian Jin4, Robert Lewandowski4,5, Robert Ryu4, Kent Sato4, Laura Kulik6, Mary Mulcahy5,7, Andrew Larson4,5, Riad Salem4,5, and Reed Omary4,5
1Siemens Medical Solutions USA, Inc., Minneapolis, Minnesota, United States, 2Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, Minnesota, United States, 3Department of Radiology, University of Illinois at Chicago, Chicago, Illinois, United States, 4Department of Radiology, Northwestern University, Chicago, Illinois, United States, 5Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois, United States,6Department of Hepatology, Northwestern University, Chicago, Illinois, United States, 7Department of Medicine, Northwestern University, Chicago, Illinois, United States

In this study, we tested the hypothesis that TRIP-MRI monitored tumor perfusion changes during TACE can predict overall survival in patients with unresectable HCC. Our study shows the evidence of association between intra-procedural tumor perfusion reduction during TACE and overall survival. TACE provided better survival benefit when relative perfusion reduction was 35-85%. The present results also suggest that TRIP-MRI performed within an integrated MR-DSA unit may serve as an intra-procedural imaging biomarker to predict survival in patients with unresectable HCC at the time of TACE procedure.

12:21 0044.   Diffusion weighted magnetic resonance imaging for pathological response prediction after neo-adjuvant radiochemotherapy for locally advanced rectal cancer.
Martijn Intven1, Onne Reerink1, and Marielle E.P. Philippens1
1Radiation Oncology, UMC Utrecht, Utrecht, Netherlands

Standard therapy for rectal cancer is neo-adjuvant therapy followed by resection. Evidence for organ-sparing therapy for good treatment responders after neo-adjuvant therapy is growing. Reliable selection of candidates for organ-sparing treatment is vital to prevent undertreatment of patients. In this study in 44 patients the predictive potential of diffusion-weighted MR Imaging for the selection of favorable responders was assessed. Both low pre-therapy ADC values and high relative ADC change (ÄADC) after neo-adjuvant therapy corresponded with pathological good response. The positive predictive value for predicting a good response was 89% for the ÄADC.

12:33 0045.   The DCE-MRI Capital Greek DeltaKtrans Biomarker Provides Early Prediction of Soft-Tissue Sarcoma Response to Anti-Angiogenic Therapy
Janelle M Meyer1, Brooke R Beckett1, Xin Li1, Luminita A Tudorica1, Aneela Afzal1, Stephanie Hemmingson1, Yiyi Chen1, Megan L Holtorf1, William J Woodward1, Charles S Springer1, Christopher W Ryan1, and Wei Huang1
1Oregon Health & Science University, Portland, Oregon, United States

Nine soft-tissue sarcoma patients underwent DCE-MRI scans during the course of a phase I trial of antiangiogenic potentiatiated preoperative chemoradiotherapy. MRI data were acquired before therapy, after two weeks of antiangiogenic therapy only, and after eight more weeks of antiangiogenic therapy plus chemoradiotherapy. The % changes in tumor ROI and histogram median ÄKtrans values after two weeks provided superior early prediction of therapy pathologic response compared to those in tumor size, ADC, and other DCE-MRI parameters. ROI and median ÄKtrans changes after two weeks also exhibited a linear relationship with the % necrosis at surgery after ten weeks.