title: Computer-aided quantitative bone scan assessment of prostate cancer treatment response.
abstract: OBJECTIVE
  The development and evaluation of a computer-aided bone scan analysis technique to quantify changes in tumor burden and assess treatment effects in prostate cancer clinical trials.
  
  
  METHODS
  We have developed and report on a commercial fully automated computer-aided detection (CAD) system. Using this system, scan images were intensity normalized, and then lesions were identified and segmented by anatomic region-specific intensity thresholding. Detected lesions were compared against expert markings to assess the accuracy of the CAD system. The metrics Bone Scan Lesion Area, Bone Scan Lesion Intensity, and Bone Scan Lesion Count were calculated from identified lesions, and their utility in assessing treatment effects was evaluated by analyzing before and after scans from metastatic castration-resistant prostate cancer patients: 10 treated and 10 untreated. In this study, patients were treated with cabozantinib, a MET/vascular endothelial growth factor inhibitor resulting in high rates of resolution of bone scan abnormalities.
  
  
  RESULTS
  Our automated CAD system identified bone lesion pixels with 94% sensitivity, 89% specificity, and 89% accuracy. Significant differences in changes from baseline were found between treated and untreated groups in all assessed measurements derived by our system. The most significant measure, Bone Scan Lesion Area, showed a median (interquartile range) change from baseline at week 6 of 7.13% (27.61) in the untreated group compared with -73.76% (45.38) in the cabozantinib-treated group (P=0.0003).
  
  
  CONCLUSIONS
  Our system accurately and objectively identified and quantified metastases in bone scans, allowing for interpatient and intrapatient comparison. It demonstrates potential as an objective measurement of treatment effects, laying the foundation for validation against other clinically relevant outcome measures.
authors.affiliation: Department of Radiological Sciences, Center for Computer Vision and Imaging Biomarkers, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California 90024, USA. mbrown@mednet.ucla.edu
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Brown
authors.forename: Gregory H
authors.initials: GH
authors.lastname: Chu
authors.forename: Hyun J
authors.initials: HJ
authors.lastname: Kim
authors.forename: Martin
authors.initials: M
authors.lastname: Allen-Auerbach
authors.forename: Cheryce
authors.initials: C
authors.lastname: Poon
authors.forename: Juliette
authors.initials: J
authors.lastname: Bridges
authors.forename: Adria
authors.initials: A
authors.lastname: Vidovic
authors.forename: Bharath
authors.initials: B
authors.lastname: Ramakrishna
authors.forename: Judy
authors.initials: J
authors.lastname: Ho
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Morris
authors.forename: Steven M
authors.initials: SM
authors.lastname: Larson
authors.forename: Howard I
authors.initials: HI
authors.lastname: Scher
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Goldin
mesh_terms: D000813:Anilides / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000000981:diagnostic imaging* / Q000556:secondary; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008297:Male; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000473:pathology; D011725:Pyridines / Q000627:therapeutic use; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D012680:Sensitivity and Specificity; D013669:Technetium Tc 99m Medronate; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects; D051598:Whole Body Imaging
chemical_list: D000813:Anilides; D011725:Pyridines; D019275:Radiopharmaceuticals; C558660:cabozantinib; D013669:Technetium Tc 99m Medronate