Diffusion-weighted Imaging as a Treatment Response Biomarker for Evaluating Bone Metastases in Prostate Cancer: A Pilot Study.
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Date
2017-04-01ICR Author
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
Show full item recordAbstract
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.
Collections
Subject
Humans
Bone Neoplasms
Prostatic Neoplasms
Piperazines
Phthalazines
Antineoplastic Agents
Diffusion Magnetic Resonance Imaging
Treatment Outcome
Prospective Studies
Pilot Projects
Image Processing, Computer-Assisted
Adult
Aged
Middle Aged
Male
Whole Body Imaging
Biomarkers, Tumor
Research team
Clinical Trials & Statistics Unit
ICR-CTSU Urology and Head and Neck Trials Team
Prostate Cancer Targeted Therapy Group
Computational Imaging
Magnetic Resonance
Language
eng
Date accepted
2016-08-01
License start date
2017-04
Citation
Radiology, 2017, 283 (1), pp. 168 - 177
Publisher
RADIOLOGICAL SOC NORTH AMERICA