title: Diffusion-weighted Imaging as a Treatment Response Biomarker for Evaluating Bone Metastases in Prostate Cancer: A Pilot Study.
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.
authors.affiliation: From the Inst of Cancer Research and Royal Marsden NHS Foundation Trust, Cancer Therapeutics Div, 15 Cotswold Rd, Sutton SM2 5NG, England.
authors.forename: Raquel
authors.initials: R
authors.lastname: Perez-Lopez
authors.affiliation: From the Inst of Cancer Research and Royal Marsden NHS Foundation Trust, Cancer Therapeutics Div, 15 Cotswold Rd, Sutton SM2 5NG, England.
authors.forename: Joaquin
authors.initials: J
authors.lastname: Mateo
authors.affiliation: From the Inst of Cancer Research and Royal Marsden NHS Foundation Trust, Cancer Therapeutics Div, 15 Cotswold Rd, Sutton SM2 5NG, England.
authors.forename: Helen
authors.initials: H
authors.lastname: Mossop
authors.affiliation: From the Inst of Cancer Research and Royal Marsden NHS Foundation Trust, Cancer Therapeutics Div, 15 Cotswold Rd, Sutton SM2 5NG, England.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Blackledge
authors.affiliation: From the Inst of Cancer Research and Royal Marsden NHS Foundation Trust, Cancer Therapeutics Div, 15 Cotswold Rd, Sutton SM2 5NG, England.
authors.forename: David J
authors.initials: DJ
authors.lastname: Collins
authors.affiliation: From the Inst of Cancer Research and Royal Marsden NHS Foundation Trust, Cancer Therapeutics Div, 15 Cotswold Rd, Sutton SM2 5NG, England.
authors.forename: Mihaela
authors.initials: M
authors.lastname: Rata
authors.affiliation: From the Inst of Cancer Research and Royal Marsden NHS Foundation Trust, Cancer Therapeutics Div, 15 Cotswold Rd, Sutton SM2 5NG, England.
authors.forename: Veronica A
authors.initials: VA
authors.lastname: Morgan
authors.affiliation: From the Inst of Cancer Research and Royal Marsden NHS Foundation Trust, Cancer Therapeutics Div, 15 Cotswold Rd, Sutton SM2 5NG, England.
authors.forename: Alison
authors.initials: A
authors.lastname: Macdonald
authors.affiliation: From the Inst of Cancer Research and Royal Marsden NHS Foundation Trust, Cancer Therapeutics Div, 15 Cotswold Rd, Sutton SM2 5NG, England.
authors.forename: Shahneen
authors.initials: S
authors.lastname: Sandhu
authors.affiliation: From the Inst of Cancer Research and Royal Marsden NHS Foundation Trust, Cancer Therapeutics Div, 15 Cotswold Rd, Sutton SM2 5NG, England.
authors.forename: David
authors.initials: D
authors.lastname: Lorente
authors.affiliation: From the Inst of Cancer Research and Royal Marsden NHS Foundation Trust, Cancer Therapeutics Div, 15 Cotswold Rd, Sutton SM2 5NG, England.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Rescigno
authors.affiliation: From the Inst of Cancer Research and Royal Marsden NHS Foundation Trust, Cancer Therapeutics Div, 15 Cotswold Rd, Sutton SM2 5NG, England.
authors.forename: Zafeiris
authors.initials: Z
authors.lastname: Zafeiriou
authors.affiliation: From the Inst of Cancer Research and Royal Marsden NHS Foundation Trust, Cancer Therapeutics Div, 15 Cotswold Rd, Sutton SM2 5NG, England.
authors.forename: Diletta
authors.initials: D
authors.lastname: Bianchini
authors.affiliation: From the Inst of Cancer Research and Royal Marsden NHS Foundation Trust, Cancer Therapeutics Div, 15 Cotswold Rd, Sutton SM2 5NG, England.
authors.forename: Nuria
authors.initials: N
authors.lastname: Porta
authors.affiliation: From the Inst of Cancer Research and Royal Marsden NHS Foundation Trust, Cancer Therapeutics Div, 15 Cotswold Rd, Sutton SM2 5NG, England.
authors.forename: Emma
authors.identifier: http://orcid.org/0000-0001-5999-5020
authors.initials: E
authors.lastname: Hall
authors.affiliation: From the Inst of Cancer Research and Royal Marsden NHS Foundation Trust, Cancer Therapeutics Div, 15 Cotswold Rd, Sutton SM2 5NG, England.
authors.forename: Martin O
authors.identifier: http://orcid.org/0000-0002-0756-5368
authors.initials: MO
authors.lastname: Leach
authors.affiliation: From the Inst of Cancer Research and Royal Marsden NHS Foundation Trust, Cancer Therapeutics Div, 15 Cotswold Rd, Sutton SM2 5NG, England.
authors.forename: Johann S
authors.initials: JS
authors.lastname: de Bono
authors.affiliation: From the Inst of Cancer Research and Royal Marsden NHS Foundation Trust, Cancer Therapeutics Div, 15 Cotswold Rd, Sutton SM2 5NG, England.
authors.forename: Dow-Mu
authors.initials: DM
authors.lastname: Koh
authors.affiliation: From the Inst of Cancer Research and Royal Marsden NHS Foundation Trust, Cancer Therapeutics Div, 15 Cotswold Rd, Sutton SM2 5NG, England.
authors.forename: Nina
authors.initials: N
authors.lastname: Tunariu
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D001859:Bone Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000556:secondary*; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D010793:Phthalazines / Q000627:therapeutic use; D010865:Pilot Projects; D010879:Piperazines / Q000627:therapeutic use; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000473:pathology*; D016896:Treatment Outcome; D051598:Whole Body Imaging
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D010793:Phthalazines; D010879:Piperazines; C531550:olaparib