title: Analysis of the changes induced by bevacizumab using a high temporal resolution DCE-MRI as prognostic factors for response to further neoadjuvant chemotherapy.
abstract: BACKGROUND
  Antiangiogenic drugs are being used in the treatment of locally advanced breast cancer. The effect of these drugs can be monitorized using high temporal resolution dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).
  
  
  OBJECTIVE
  To evaluate changes in tumor microvasculature induced by bevacizumab and the usefulness of these changes predicting response to further neoadjuvant therapy.
  
  
  METHODS
  Seventy patients with locally advanced breast cancers were treated with one cycle of bevacizumab followed by neoadjuvant therapy, combining bevacizumab and cytotoxic chemotherapy. Two DCE-MRI were performed before and after bevacizumab. Changes in tumoral volume, pharmacodynamic curves, and pharmacokinetic variables (K(trans), Kep, Ve, AUC90) in a ROI (ROI 1) encompassing the entire tumor and in another ROI (ROI 2) in the area of higher values of K(trans) were analyzed. Correlations with pathological response were made: parametrical and non-parametrical statistical analysis and ROC curves were used; a P < 0.05 was considered significant.
  
  
  RESULTS
  Significant changes in tumoral volume (-4%), pharmacodynamic curves, and pharmacokinetic variables in ROI 1 K(trans) (-45%), Kep (-38%), Ve (-11%), and AUC90 (-44%) and ROI 2 K(trans) (-43%), Kep (-39%), Ve (-5%), and AUC90 (-45%) were observed after bevacizumab (P < 0.05). The effect of bevacizumab was not different between responders and non-responders (P > 0.05), and these changes could not predict response to further neoadjuvant therapy.
  
  
  CONCLUSIONS
  Bevacizumab induces remarkable tumoral volume, pharmacodynamics, and pharmacokinetic changes. However, these changes could not be used as early predictors for response to further neoadjuvant therapy.
authors.affiliation: Department of Radiology, Clínica Universidad de Navarra, Pamplona, Navarra, Spain Etxanojon@gmail.com.
authors.forename: Jon
authors.initials: J
authors.lastname: Etxano
authors.affiliation: Department of Radiology, Clínica Universidad de Navarra, Pamplona, Navarra, Spain.
authors.forename: Luis Pina
authors.initials: LP
authors.lastname: Insausti
authors.affiliation: Department of Radiology, Clínica Universidad de Navarra, Pamplona, Navarra, Spain.
authors.forename: Arlette
authors.initials: A
authors.lastname: Elizalde
authors.affiliation: Department of Oncology, Hospital Universitario Marqués de Valdecilla, Santander, Cantabria, Spain.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: López Vega
authors.affiliation: Department of Oncology, Instituto Oncológico, San Sebastián, Guipuzcoa, Spain.
authors.forename: Arrate
authors.initials: A
authors.lastname: Plazaola
authors.affiliation: Department of Oncology, Hospital de Basurto, Bilbao, Bizkaia, Spain.
authors.forename: Purificación
authors.initials: P
authors.lastname: Martínez
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D009942:Organometallic Compounds; D011379:Prognosis; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D009942:Organometallic Compounds; C090600:gadobutrol; D000068258:Bevacizumab
keywords: Breast neoplasms; bevacizumab; magnetic resonance imaging (MRI); neoadjuvant treatment; pharmacodynamic; pharmacokinetics