Messiou, C., Orton, M., Ang, J. E., Collins, D. J., Morgan, V. A., Mears, D., Castellano, I., Papadatos-Pastos, D., Brunetto, A., Tunariu, N., Mann, H., Tessier, J., Young, H., Ghiorghiu, D., Marley, S., Kaye, S. B., deBono, J. S., Leach, M. O., deSouza, N. M. (2012) Advanced Solid Tumors Treated with Cediranib: Comparison of Dynamic Contrast-enhanced MR Imaging and CT as Markers of Vascular Activity. RADIOLOGY, 265 (2). pp. 426-436. ISSN 0033-8419

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Abstract

Purpose: To assess baseline reproducibility and compare performance of dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging versus DCE computed tomographic (CT) measures of early vascular response in the same patients treated with cediranib (30 or 45 mg daily). Materials and Methods: After institutional review board approval, written informed consent was obtained from 29 patients with advanced solid tumors who had lesions 3 cm or larger and in whom simultaneous imaging of an adjacent artery was possible. Two baseline DCE MR acquisitions and two baseline DCE CT acquisitions 7 days or fewer apart (within 14 days of starting treatment) and two posttreatment acquisitions with each modality at day 7 and 28 (+/- 3 days) were obtained. Nonmodeled and modeled parameters were derived (measured arterial input function [AIF] for CT, population-based AIF for MR imaging; temporal sampling rate of 0.5 second for CT, 3-6 seconds for MR imaging). Baseline variability was assessed by using intra-and intersubject analysis of variance and Bland-Altman analysis; a paired t test assessed change from baseline to after treatment. Results: The most reproducible parameters were DCE MR imaging enhancement fraction (baseline intrapatient coefficient of variation [CV] = 8.6%), volume transfer constant (CV = 13.9%), and integrated area under the contrast uptake curve at 60 seconds (CV = 15.5%) and DCE CT positive enhancement integral (CV = 16.0%). Blood plasma volume was highly variable and the only parameter with CV greater than 30%. Average reductions (percentage change) from baseline were consistently observed for all DCE MR imaging and DCE CT parameters at day 7 and 28 for both starting-dose groups (45 and 30 mg), except for DCE CT mean transit time. Percentage change from baseline for parameters reflecting blood flow and permeability were comparable, and reductions from baseline at day 7 were maintained at day 28. Conclusion: DCE MR imaging and DCE CT can depict vascular response to antiangiogenic agents with response evident at day 7. Improved reproducibility with MR imaging favors its use in trials with small patient numbers.

Item Type:	Article
Authors (ICR Faculty only):	Kaye, Stan and De-Bono, Johann and Leach, Martin and Desouza, Nandita
All Authors:	Messiou, C., Orton, M., Ang, J. E., Collins, D. J., Morgan, V. A., Mears, D., Castellano, I., Papadatos-Pastos, D., Brunetto, A., Tunariu, N., Mann, H., Tessier, J., Young, H., Ghiorghiu, D., Marley, S., Kaye, S. B., deBono, J. S., Leach, M. O., deSouza, N. M.
Additional Information:	ISI Document Delivery No.: 029PN Times Cited: 0 Cited Reference Count: 38 Messiou, Christina Orton, Matthew Ang, Joo Ern Collins, David J. Morgan, Veronica A. Mears, Dorothy Castellano, Isabel Papadatos-Pastos, Dionysis Brunetto, Andre Tunariu, Nina Mann, Helen Tessier, Jean Young, Helen Ghiorghiu, Dana Marley, Sarah Kaye, Stan B. deBono, Johann S. Leach, Martin O. deSouza, Nandita M. AstraZeneca; Cancer Research UK; EPSRC Cancer Imaging Centre; Medical Research Council; Department of Health (England) [C1060/A10334]; Experimental Cancer Medicine Centre; National Institute for Health Research Biomedical Research Centre This work was funded by AstraZeneca. We also acknowledge support for the Cancer Research UK and EPSRC Cancer Imaging Centre in association with the Medical Research Council and Department of Health (England; grant C1060/A10334). The Drug Development Unit is supported in part by a program grant from Cancer Research UK. Support was also provided by the Experimental Cancer Medicine Centre (to the Institute of Cancer Research) and the National Institute for Health Research Biomedical Research Centre. Radiological soc north america Oak brook
Uncontrolled Keywords:	quantitative measurements perfusion parameters clinical-trials liver-tumors reproducibility azd2171 model agreement cancer lung
Research teams:	ICR divisions > Cancer Therapeutics > Cancer Biomarkers ICR divisions > Clinical Studies > Cancer Biomarkers ICR divisions > Radiotherapy and Imaging > Magnetic Resonance ICR divisions > Clinical Studies > Prostate Cancer Targeted Therapy Group
Depositing User:	Users 11 not found.
Date Deposited:	30 Nov 2012 15:28
Last Modified:	11 Jul 2017 14:42
URI:	http://publications.icr.ac.uk/id/eprint/12070

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