title: Multi-parametric MRI in the early prediction of response to neo-adjuvant chemotherapy in breast cancer: Value of non-modelled parameters.
abstract: OBJECTIVE
  To prospectively evaluate individual functional MRI metrics for the early prediction of pathological complete response (pCR) to neo-adjuvant chemotherapy (NAC) in breast cancer.
  
  
  METHODS
  Thirty-two women (median age 52 years; range 32-71 years) with biopsy proven breast cancer due to receive neo-adjuvant anthracycline and/or taxane-based chemotherapy were prospectively recruited following local research ethics committee approval and written informed consent. Breast MRI was performed prior to and after two cycles of NAC and pCR was assessed after surgery. The enhancement fraction (EF), tumour volume, initial area under the gadolinium curve (IAUGC), pharmacokinetic parameters (K(trans), kep and ve), the apparent diffusion coefficient (ADC) and R2* values, along with the percentage change in these parameters after two cycles were evaluated according to pCR status using an independent samples t-test. The area under the receiver operating characteristics curve (AUC) was calculated for each parameter. Linear discriminant analysis (LDA) determined the most important parameter in predicting pCR.
  
  
  RESULTS
  A reduction in the EF (-41% ± 38%) and tumour volume (-80% ± 25%) after 2 cycles of NAC were significantly greater in those achieving pCR (p=0.025, p=0.011 respectively). A reduction in the EF of 7% after 2 cycles of NAC identified those more likely to achieve pCR (AUC 0.76). AUC changes in other parameters were tumour volume (0.77), IAUGC (0.64), K(trans) (0.60), kep (0.68), ve (0.58), ADC (0.69) and R2* (0.41).
  
  
  CONCLUSIONS
  In a multi-parametric MRI model, the decrease in a non-model based vascular parameter the enhancement fraction as well as the tumour volume are the most important early predictors of pCR in breast cancer.
authors.affiliation: Clinical Magnetic Resonance Group, Cancer Research UK Cancer Imaging Centre, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey SM2 5PT, United Kingdom. Electronic address: Elizabeth.OFlynn@icr.ac.uk.
authors.forename: Elizabeth A M
authors.initials: EA
authors.lastname: O'Flynn
authors.affiliation: Clinical Magnetic Resonance Group, Cancer Research UK Cancer Imaging Centre, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey SM2 5PT, United Kingdom. Electronic address: david.collins@icr.ac.uk.
authors.forename: David
authors.initials: D
authors.lastname: Collins
authors.affiliation: Clinical Magnetic Resonance Group, Cancer Research UK Cancer Imaging Centre, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey SM2 5PT, United Kingdom. Electronic address: james.darcy@icr.ac.uk.
authors.forename: James
authors.initials: J
authors.lastname: D'Arcy
authors.affiliation: Clinical Magnetic Resonance Group, Cancer Research UK Cancer Imaging Centre, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey SM2 5PT, United Kingdom. Electronic address: maria.schmidt@rmh.nhs.uk.
authors.forename: Maria
authors.initials: M
authors.lastname: Schmidt
authors.affiliation: Clinical Magnetic Resonance Group, Cancer Research UK Cancer Imaging Centre, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey SM2 5PT, United Kingdom. Electronic address: Nandita.desouza@icr.ac.uk.
authors.forename: Nandita M
authors.initials: NM
authors.lastname: de Souza
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018943:Anthracyclines / Q000008:administration & dosage / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D019540:Area Under Curve; D001943:Breast Neoplasms / Q000188:drug therapy*; D001952:Bridged-Ring Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D005260:Female; D005544:Forecasting; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008408:Mastectomy / Q000379:methods; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D011446:Prospective Studies; D012372:ROC Curve; D012074:Remission Induction; D043823:Taxoids / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects; D055815:Young Adult
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D043823:Taxoids; C080625:taxane
keywords: Enhancement fraction; Multi-parametric MRI; Predicting pCR