title: 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.
abstract: (18)F-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 (18)F-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 (18)F-fluoride incorporation in tumor and normal bone occurred in response to dasatinib. Other endpoints included differential effect of dasatinib between (18)F-fluoride incorporation in tumor and normal bone, (18)F-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 (18)F-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 (18)F-fluoride PET response between tumor and normal bone (P < 0.0001). Changes in (18)F-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).
  
  
  CONCLUSIONS
  This trial provides evidence of the ability (18)F-fluoride PET to delineate treatment response of dasatinib in CRPC bone metastases with borderline correlation with PFS.
authors: University of Washington, Seattle, Washington evanyu@uw.edu.
authors: Evan Y
authors: EY
authors: Yu
authors: Department of Biostatistics and Center for Statistical Sciences, Brown University School of Public Health, Providence, Rhode Island.
authors: Fenghai
authors: F
authors: Duan
authors: University of Washington, Seattle, Washington.
authors: Mark
authors: M
authors: Muzi
authors: Department of Biostatistics and Center for Statistical Sciences, Brown University School of Public Health, Providence, Rhode Island.
authors: Xuan
authors: X
authors: Deng
authors: Duke University, Durham, North Carolina.
authors: Bennett B
authors: BB
authors: Chin
authors: Oregon Health & Science University, Portland, Oregon.
authors: Joshi J
authors: JJ
authors: Alumkal
authors: Dana-Farber Cancer Institute, Boston, Massachusetts.
authors: Mary-Ellen
authors: ME
authors: Taplin
authors: University of Washington, Seattle, Washington.
authors: Jina M
authors: JM
authors: Taub
authors: Department of Biostatistics and Center for Statistical Sciences, Brown University School of Public Health, Providence, Rhode Island.
authors: Ben
authors: B
authors: Herman
authors: University of Washington, Seattle, Washington.
authors: Celestia S
authors: CS
authors: Higano
authors: University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Robert K
authors: RK
authors: Doot
authors: American College of Radiology Imaging Network (ACRIN), Philadelphia, Pennsylvania; and.
authors: Donna
authors: D
authors: Hartfeil
authors: University of California San Francisco, San Francisco, California.
authors: Philip G
authors: PG
authors: Febbo
authors: University of Pennsylvania, Philadelphia, Pennsylvania.
authors: David A
authors: DA
authors: Mankoff
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001706:Biopsy; D001859:Bone Neoplasms / Q000000981:diagnostic imaging / Q000556:secondary; D001842:Bone and Bones / Q000473:pathology; D000069439:Dasatinib; D018572:Disease-Free Survival; D005462:Fluorine Radioisotopes; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D049268:Positron-Emission Tomography; D064129:Prostatic Neoplasms, Castration-Resistant / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use*; D011944:Receptors, Androgen / Q000378:metabolism; D013844:Thiazoles / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D005462:Fluorine Radioisotopes; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011944:Receptors, Androgen; D013844:Thiazoles; D000069439:Dasatinib
keywords: 18F-fluoride PET; bone metastases; dasatinib; metastatic castration-resistant prostate cancer
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