title: Optimized breast MRI functional tumor volume as a biomarker of recurrence-free survival following neoadjuvant chemotherapy.
abstract: OBJECTIVE
  To evaluate optimal contrast kinetics thresholds for measuring functional tumor volume (FTV) by breast magnetic resonance imaging (MRI) for assessment of recurrence-free survival (RFS).
  
  
  METHODS
  In this Institutional Review Board (IRB)-approved retrospective study of 64 patients (ages 29-72, median age of 48.6) undergoing neoadjuvant chemotherapy (NACT) for breast cancer, all patients underwent pre-MRI1 and postchemotherapy MRI4 of the breast. Tumor was defined as voxels meeting thresholds for early percent enhancement (PEthresh) and early-to-late signal enhancement ratio (SERthresh); and FTV (PEthresh, SERthresh) by summing all voxels meeting threshold criteria and minimum connectivity requirements. Ranges of PEthresh from 50% to 220% and SERthresh from 0.0 to 2.0 were evaluated. A Cox proportional hazard model determined associations between change in FTV over treatment and RFS at different PE and SER thresholds.
  
  
  RESULTS
  The plot of hazard ratios for change in FTV from MRI1 to MRI4 showed a broad peak with the maximum hazard ratio and highest significance occurring at PE threshold of 70% and SER threshold of 1.0 (hazard ratio = 8.71, 95% confidence interval 2.86-25.5, P < 0.00015), indicating optimal model fit.
  
  
  CONCLUSIONS
  Enhancement thresholds affect the ability of MRI tumor volume to predict RFS. The value is robust over a wide range of thresholds, supporting the use of FTV as a biomarker.
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco (UCSF), San Francisco, California, USA.
authors.forename: Nazia F
authors.initials: NF
authors.lastname: Jafri
authors.forename: David C
authors.initials: DC
authors.lastname: Newitt
authors.forename: John
authors.initials: J
authors.lastname: Kornak
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Esserman
authors.forename: Bonnie N
authors.initials: BN
authors.lastname: Joe
authors.forename: Nola M
authors.initials: NM
authors.lastname: Hylton
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000473:pathology* / Q000628:therapy*; D059186:Chemoradiotherapy, Adjuvant / Q000379:methods; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D021621:Imaging, Three-Dimensional / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods; D009364:Neoplasm Recurrence, Local / Q000473:pathology* / Q000517:prevention & control*; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D047368:Tumor Burden
keywords: MRI breast functional tumor volume; SER/PE thresholds; neoadjuvant chemotherapy