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Diffusion-weighted Imaging as a Treatment Response Biomarker for Evaluating Bone Metastases in Prostate Cancer: A Pilot Study.

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Publication Date
2017-04
ICR Author
Leach, Martin
Hall, Emma
De Bono, Johann
Rata, Mihaela
Koh, Dow-Mu
Mossop, Helen
Porta, Nuria
Rescigno, Pasquale
Tunariu, Nina
Marsden,
Author
Perez-Lopez, R
Mateo, J
Mossop, H
Blackledge, MD
Collins, DJ
Rata, M
Morgan, VA
Macdonald, A
Sandhu, S
Lorente, D
Rescigno, P
Zafeiriou, Z
Bianchini, D
Porta, N
Hall, E
Leach, MO
de Bono, JS
Koh, D-M
Tunariu, N
Type
Journal Article
Metadata
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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. Online supplemental material is available for this article.
URL
https://repository.icr.ac.uk/handle/internal/71
Collections
  • Clinical Studies
  • Radiotherapy and Imaging
Licenseref URL
https://creativecommons.org/licenses/by/4.0
Version of record
10.1148/radiol.2016160646
Subject
Adult
Aged
Antineoplastic Agents
Biomarkers, Tumor
Bone Neoplasms
Diffusion Magnetic Resonance Imaging
Humans
Image Processing, Computer-Assisted
Male
Middle Aged
Phthalazines
Pilot Projects
Piperazines
Prospective Studies
Prostatic Neoplasms
Treatment Outcome
Whole Body Imaging
Research team
Clinical Trials & Statistics Unit
ICR-CTSU Urology and Head and Neck Trials Team
Prostate Cancer Targeted Therapy Group
Magnetic Resonance
Language
eng
Date accepted
2016-08-01
License start date
2017-04
Citation
Radiology, 2017, 283 (1), pp. 168 - 177

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