Castration-resistant prostate cancer bone metastasis response measured by 18F-fluoride PET after treatment with dasatinib and correlation with progression-free survival: Results from American College of Radiology Imaging Network 6687

Evan Y. Yu, Fenghai Duan, Mark Muzi, Xuan Deng, Bennett B. Chin, Joshi J. Alumkal, Mary Ellen Taplin, Jina M. Taub, Ben Herman, Celestia S. Higano, Robert K. Doot, Donna Hartfeil, Philip G. Febbo, David A. Mankoff

    Research output: Contribution to journalArticle

    36 Scopus citations

    Abstract

    18F-fluoride PET quantitatively images bone metabolism and may serve as a pharmacodynamic assessment for systemic therapy such as dasatinib, a potent SRC kinase inhibitor, with activity in bone. Methods: This was an imaging companion trial (American College of Radiology Imaging Network [ACRIN] 6687) to a multicenter metastatic castration-resistant prostate cancer (CRPC) tissue biomarker-guided therapeutic trial (NCT00918385). Men with bone metastatic CRPC underwent 18F-fluoride PET before and 12 weeks after initiation of dasatinib (100 mg daily). Dynamic imaging was performed over a 15-cm field of view for trial assessments. The primary endpoint was to determine whether changes in 18F-fluoride incorporation in tumor and normal bone occurred in response to dasatinib. Other endpoints included differential effect of dasatinib between 18F-fluoride incorporation in tumor and normal bone, 18F-fluoride transport in bone metastases, correlation with progression-free survival (PFS), prostate-specific antigen, and markers of bone turnover. Results: Eighteen participants enrolled, and 17 underwent interpretable baseline 18F-fluoride PET imaging before initiation of dasatinib. Twelve of 17 patients underwent on-treatment PET imaging. Statistically significant changes in response to dasatinib were identified by the SUVmaxavg (average of maximum standardized uptake value [SUVmax] for up to 5 tumors within the dynamic field of view) in bone metastases (P = 0.0002), with a significant differential 18F-fluoride PET response between tumor and normal bone (P < 0.0001). Changes in 18F-fluoride incorporation in bone metastases had borderline correlation with PFS by SUVmaxavg (hazard ratio, 0.91; 95% confidence interval, 0.82-1.00; P = 0.056). Changes by SUVmaxavg correlated with bone alkaline phosphatase ( P = 0.0014) but not prostate-specific antigen (P = 0.47). Conclusion: This trial provides evidence of the ability 18F-fluoride PET to delineate treatment response of dasatinib in CRPC bone metastases with borderline correlation with PFS.

    Original languageEnglish (US)
    Pages (from-to)354-360
    Number of pages7
    JournalJournal of Nuclear Medicine
    Volume56
    Issue number3
    DOIs
    StatePublished - Mar 1 2015

    Keywords

    • <sup>18</sup>F-fluoride PET
    • Bone metastases
    • Dasatinib
    • Metastatic castration-resistant prostate cancer

    ASJC Scopus subject areas

    • Radiology Nuclear Medicine and imaging

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