Perez-Lopez, R., Mateo, J., Mossop, H., Blackledge, M. D., Collins, D. J., Rata, M., Morgan, V. A., Macdonald, A., Sandhu, S., Lorente, D., Rescigno, P., Zafeiriou, Z., Bianchini, D., Porta, N., Hall, E., Leach, M. O., de Bono, J. S., Koh, D. M., Tunariu, N. (2017) Diffusion-weighted Imaging as a Treatment Response Biomarker for Evaluating Bone Metastases in Prostate Cancer: A Pilot Study. RADIOLOGY, 283 (1). pp. 168-177. ISSN 0033-8419

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Abstract

Purpose: To determine the usefulness of whole-body diffusion-weighted imaging (DWI) to assess the response of bone metastases to treatment in patients with metastatic castration-resistant prostate cancer (mCRPC). Materials and Methods: A phase II prospective clinical trial of the poly-(adenosine diphosphate-ribose) polymerase inhibitor olaparib in mCRPC included a prospective magnetic resonance (MR) imaging substudy; the study was approved by the institutional research board, and written informed consent was obtained. Whole-body DWI was performed at baseline and after 12 weeks of olaparib administration by using 1.5-T MR imaging. Areas of abnormal signal intensity on DWI images in keeping with bone metastases were delineated to derive total diffusion volume (tDV); five target lesions were also evaluated. Associations of changes in volume of bone metastases and median apparent diffusion coefficient (ADC) with response to treatment were assessed by using the Mann-Whitney test and logistic regression; correlation with prostate-specific antigen level and circulating tumor cell count were assessed by using Spearman correlation (r). Results: Twenty-one patients were included. All six responders to olaparib showed a decrease in tDV, while no decrease was observed in all nonresponders; this difference between responders and nonresponders was significant (P = .001). Increases in median ADC were associated with increased odds of response (odds ratio, 1.08; 95% confidence interval [CI]: 1.00, 1.15; P = .04). A positive association was detected between changes in tDV and best percentage change in prostate-specific antigen level and circulating tumor cell count (r = 0.63 [95% CI: 0.27, 0.83] and r = 0.77 [95% CI: 0.51, 0.90], respectively). When assessing five target lesions, decreases in volume were associated with response (odds ratio for volume increase, 0.89; 95% CI: 0.80, 0.99; P = .037). Conclusion: This pilot study showed that decreases in volume and increases in median ADC of bone metastases assessed with whole-body DWI can potentially be used as indicators of response to olaparib in mCRPC. Published under a CC BY 4.0 license.

Item Type:	Article
Authors (ICR Faculty only):	Leach, Martin and Koh, Dow-Mu and Hall, Emma and De Bono, Johann
All Authors:	Perez-Lopez, R., Mateo, J., Mossop, H., Blackledge, M. D., Collins, D. J., Rata, M., Morgan, V. A., Macdonald, A., Sandhu, S., Lorente, D., Rescigno, P., Zafeiriou, Z., Bianchini, D., Porta, N., Hall, E., Leach, M. O., de Bono, J. S., Koh, D. M., Tunariu, N.
Additional Information:	ISI Document Delivery No.: EV6QU Times Cited: 0 Cited Reference Count: 26 Perez-Lopez, Raquel Mateo, Joaquin Mossop, Helen Blackledge, Matthew D. Collins, David J. Rata, Mihaela Morgan, Veronica A. Macdonald, Alison Sandhu, Shahneen Lorente, David Rescigno, Pasquale Zafeiriou, Zafeiris Bianchini, Diletta Porta, Nuria Hall, Emma Leach, Martin O. de Bono, Johann S. Koh, Dow-Mu Tunariu, Nina Lorente, David/B-9420-2017 BRC [BRC A38]; Stand Up to Cancer [SU2CAACR-DT0712]; Cancer Research UK; Dept of Health [CRM064X, C1060/A10334, C1060/A16464]; Cancer Research UK [C12540/A12829, C12540/A13230, C1491/A15955, C1491/A9895]; CRUK; EPSRC; MRC; Prostate Cancer UK [PG14-016-TR2]; Prostate Cancer Foundation [20131017]; AstraZeneca; National Inst for Health Research Cancer Research Network; NHS; MRC-Prostate Cancer UK Fellowship; PCF Young Investigator Award; NIHR [NHR011X]; NHS Executive Supported by BRC (BRC A38), Stand Up to Cancer (SU2CAACR-DT0712), ECMC funding from Cancer Research UK and Dept of Health (CRM064X), Cancer Research UK (C12540/A12829, C12540/A13230, C1491/A15955, C1491/A9895), CRUK and EPSRC in association with MRC and Dept of Health (C1060/A10334, C1060/A16464), Prostate Cancer UK (PG14-016-TR2), Prostate Cancer Foundation (20131017), the Investigator-Sponsored Study Collaboration between AstraZeneca and the National Inst for Health Research Cancer Research Network, and NHS funding to the NIHR Biomedicine Research Ctr and Clinical Research Facility. J.M. supported by the MRC-Prostate Cancer UK Fellowship and a PCF Young Investigator Award. M.D.B. supported by the NIHR postdoctoral fellowship (NHR011X).; This work was undertaken at The Royal Marsden NHS Foundation Trust, which received a proportion of its funding from the NHS Executive; the views expressed in this publication are those of the authors and not necessarily those of the NHS Executive. M.O.L. is an NIHR senior investigator. 0 RADIOLOGICAL SOC NORTH AMERICA OAK BROOK RADIOLOGY
Uncontrolled Keywords:	END-POINTS SURVIVAL CELLULARITY PATTERNS ANTIGEN TUMORS
Research teams:	ICR divisions > Cancer Therapeutics > Cancer Biomarkers ICR divisions > Clinical Studies > Cancer Biomarkers ICR divisions > Clinical Studies > ICR-CTSU Urology and Head and Neck Trials Team ICR divisions > Radiotherapy and Imaging > Magnetic Resonance Clinical Units > Department of Diagnostic Radiology ICR divisions > Clinical Studies > Prostate Cancer Targeted Therapy Group
Depositing User:	Barry Jenkins
Date Deposited:	12 Jun 2017 14:17
Last Modified:	12 Jun 2017 14:17
URI:	http://publications.icr.ac.uk/id/eprint/16010

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