title: Assessment of the bone scan index in a randomized placebo-controlled trial of tasquinimod in men with metastatic castration-resistant prostate cancer (mCRPC).
abstract: BACKGROUND
  Drug development and clinical decision making for patients with metastatic prostate cancer (PC) have been hindered by a lack of quantitative methods of assessing changes in bony disease burden that are associated with overall survival (OS). Bone scan index (BSI), a quantitative imaging biomarker of bone tumor burden, is prognostic in men with metastatic PC. We evaluated an automated method for BSI calculation for the association between BSI over time with clinical outcomes in a randomized double-blind trial of tasquinimod (TASQ) in men with metastatic castration-resistant PC (mCRPC).
  
  
  METHODS
  Bone scans collected during central review from the TASQ trial were analyzed retrospectively using EXINIbone(BSI), an automated software package for BSI calculation. Associations between BSI and other prognostic biomarkers, progression-free survival, OS, and treatment were evaluated over time.
  
  
  RESULTS
  Of 201 men (57 TASQ and 28 placebo), 85 contributed scans at baseline and week 12 of sufficient quality. Baseline BSI correlated with prostate-specific antigen and alkaline phosphatase levels and was associated with OS in univariate (hazard ratio [HR] = 1.42, P = 0.013) and multivariate (HR = 1.64, P<0.001) analyses. BSI worsening at 12 weeks was prognostic for progression-free survival (HR = 2.14 per BSI doubling, P<0.001) and OS (HR = 1.58, P = 0.033) in multivariate analyses including baseline BSI and TASQ treatment. TASQ delayed BSI progression.
  
  
  CONCLUSIONS
  BSI and BSI changes over time were independently associated with OS in men with mCRPC. A delay in objective radiographic bone scan progression with TASQ is suggested; prospective evaluation of BSI progression and response criteria in phase 3 trials of men with mCRPC is warranted.
authors.affiliation: Duke Cancer Institute and the Duke Prostate Center, Duke University, Durham, NC. Electronic address: andrew.armstrong@duke.edu.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Armstrong
authors.affiliation: Department of Molecular and Clinical Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
authors.forename: Reza
authors.initials: R
authors.lastname: Kaboteh
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Carducci
authors.affiliation: Department of Urology, Institute of Clinical Sciences, Gothenburg University, Gothenburg, Sweden.
authors.forename: Jan-Erik
authors.initials: JE
authors.lastname: Damber
authors.affiliation: Department of Medicine, University of Chicago, Chicago, IL.
authors.forename: Walter M
authors.initials: WM
authors.lastname: Stadler
authors.affiliation: Active Biotech AB, Lund, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Hansen
authors.affiliation: Department of Molecular and Clinical Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Department of Clinical Sciences, Lund University, Malmö, Sweden; EXINI Diagnostics AB, Lund, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Edenbrandt
authors.affiliation: Active Biotech AB, Lund, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Forsberg
authors.affiliation: Active Biotech AB, Lund, Sweden.
authors.forename: Örjan
authors.initials: Ö
authors.lastname: Nordle
authors.affiliation: Roswell Park Cancer Institute Genitourinary Program, Buffalo, NY.
authors.forename: Roberto
authors.initials: R
authors.lastname: Pili
authors.affiliation: Genitourinary Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY; Department of Medicine, Weill Cornell Medical College, New York, NY.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Morris
mesh_terms: D001859:Bone Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000556:secondary*; D001842:Bone and Bones / Q000000981:diagnostic imaging*; D003952:Diagnostic Imaging / Q000379:methods*; D018450:Disease Progression; D018572:Disease-Free Survival; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D011379:Prognosis; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000473:pathology*; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015363:Quinolones; D011859:Radiography; D012189:Retrospective Studies
chemical_list: D011804:Quinolines; D015363:Quinolones; C516109:tasquinimod
keywords: Automated detection; Bone metastases; Computer-assisted diagnosis; Image analysis; Progression-free survival; Prostate cancer; Radionuclide imaging; Tasquinimod