title: Multi-site clinical evaluation of DW-MRI as a treatment response metric for breast cancer patients undergoing neoadjuvant chemotherapy.
abstract: OBJECTIVE
  To evaluate diffusion weighted MRI (DW-MR) as a response metric for assessment of neoadjuvant chemotherapy (NAC) in patients with primary breast cancer using prospective multi-center trials which provided MR scans along with clinical outcome information.
  
  
  METHODS
  A total of 39 patients with locally advanced breast cancer accrued from three different prospective clinical trials underwent DW-MR examination prior to and at 3-7 days (Hull University), 8-11 days (University of Michigan) and 35 days (NeoCOMICE) post-treatment initiation. Thirteen patients, 12 of which participated in treatment response study, from UM underwent short interval (<1hr) MRI examinations, referred to as "test-retest" for examination of repeatability. To further evaluate stability in ADC measurements, a thermally controlled diffusion phantom was used to assess repeatability of diffusion measurements. MRI sequences included contrast-enhanced T1-weighted, when appropriate, and DW images acquired at b-values of 0 and 800 s/mm2. Histogram analysis and a voxel-based analytical technique, the Parametric Response Map (PRM), were used to derive diffusion response metrics for assessment of treatment response prediction.
  
  
  RESULTS
  Mean tumor apparent diffusion coefficient (ADC) values generated from patient test-retest examinations were found to be very reproducible (|ΔADC|<0.1x10-3mm2/s). This data was used to calculate the 95% CI from the linear fit of tumor voxel ADC pairs of co-registered examinations (±0.45x10-3mm2/s) for PRM analysis of treatment response. Receiver operating characteristic analysis identified the PRM metric to be predictive of outcome at the 8-11 (AUC = 0.964, p = 0.01) and 35 day (AUC = 0.770, p = 0.05) time points (p<.05) while whole-tumor ADC changes where significant at the later 35 day time interval (AUC = 0.825, p = 0.02).
  
  
  CONCLUSIONS
  This study demonstrates the feasibility of performing a prospective analysis of DW-MRI as a predictive biomarker of NAC in breast cancer patients. In addition, we provide experimental evidence supporting the use of sensitive analytical tools, such as PRM, for evaluating ADC measurements.
authors: Departments of Radiology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Craig J
authors: CJ
authors: Galbán
authors: Departments of Radiology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Bing
authors: B
authors: Ma
authors: Departments of Radiology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Dariya
authors: D
authors: Malyarenko
authors: Centre for MR Investigations, Hull York Medical School, University of Hull, Hull, United Kingdom.
authors: Martin D
authors: MD
authors: Pickles
authors: Departments of Radiology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Kevin
authors: K
authors: Heist
authors: Departments of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Norah L
authors: NL
authors: Henry
authors: Departments of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Anne F
authors: AF
authors: Schott
authors: Departments of Radiology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Colleen H
authors: CH
authors: Neal
authors: Department of Radiology, University of California San Francisco, San Francisco, California, United States of America.
authors: Nola M
authors: NM
authors: Hylton
authors: Departments of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Alnawaz
authors: A
authors: Rehemtulla
authors: Departments of Biostatistics, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Timothy D
authors: TD
authors: Johnson
authors: Departments of Radiology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Charles R
authors: CR
authors: Meyer
authors: Departments of Radiology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Thomas L
authors: TL
authors: Chenevert
authors: Centre for MR Investigations, Hull York Medical School, University of Hull, Hull, United Kingdom.
authors: Lindsay W
authors: LW
authors: Turnbull
authors: Departments of Radiology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Brian D
authors: BD
authors: Ross
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D017024:Chemotherapy, Adjuvant; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome