title: Metastatic ovarian and primary peritoneal cancer: assessing chemotherapy response with diffusion-weighted MR imaging--value of histogram analysis of apparent diffusion coefficients.
abstract: OBJECTIVE
  To prospectively evaluate apparent diffusion coefficient (ADC) histograms in the prediction of chemotherapy response in patients with metastatic ovarian or primary peritoneal cancer.
  
  
  METHODS
  Research ethics committee approval and patient written informed consent were obtained. Diffusion-weighted (DW) magnetic resonance (MR) imaging was performed through the abdomen and pelvis before and after one and three cycles of chemotherapy in 42 women (mean age, 63.0 years ± 11.4 [standard deviation]) with newly diagnosed or recurrent disease. Reproducibility and intra- and interobserver agreement of ADC calculations were assessed. Per-patient weighted ADC histograms were generated at each time point from pixel ADCs from five or fewer target lesions. Mean ADC, percentiles (10th, 25th, 50th, 75th, 90th), skew, kurtosis, and their change were analyzed according to histologic grade, primary versus recurrent disease status, and response, determined with integrated biochemical and morphologic criteria, with a linear mixed model. Areas under receiver operating characteristic curve (AUCs) for combinations of parameters were calculated with linear discriminant analysis.
  
  
  RESULTS
  Coefficients of variation for repeat measurements and for within and between observers were 4.8%, 11.4%, and 13.7%, respectively. Grade and disease status did not significantly affect histogram parameters. Pretreatment ADCs were not predictive of response. In responders, all ADCs increased after the first and third cycle (P < .001), while skew and kurtosis decreased after the third (P < .001 and P = .006, respectively); however, in nonresponders, no parameter changed significantly. Percentage change of the 25th percentile performed best in identifying response (AUC = 0.82 and 0.83 after first and third cycle, respectively), whereas combination of parameters did not improve accuracy.
  
  
  CONCLUSIONS
  An early increase of ADCs and later decrease of skew and kurtosis characterize chemotherapy response. Quantitative DW MR imaging can aid in early monitoring of treatment efficacy in patients with advanced ovarian cancer.
authors.affiliation: Cancer Research-UK and EPSRC Cancer Imaging Centre, Research Data Management and Statistics Unit, and Department of Gynaecological Oncology, Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Sutton, Surrey SM2 5PT, England. Stavroula.Kyriazi@icr.ac.uk
authors.forename: Stavroula
authors.initials: S
authors.lastname: Kyriazi
authors.forename: David J
authors.initials: DJ
authors.lastname: Collins
authors.forename: Christina
authors.initials: C
authors.lastname: Messiou
authors.forename: Kjell
authors.initials: K
authors.lastname: Pennert
authors.forename: Robert L
authors.initials: RL
authors.lastname: Davidson
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Giles
authors.forename: Stan B
authors.initials: SB
authors.lastname: Kaye
authors.forename: Nandita M
authors.initials: NM
authors.lastname: Desouza
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D011446:Prospective Studies; D016896:Treatment Outcome