title: Assessment of early treatment response to neoadjuvant chemotherapy in breast cancer using non-mono-exponential diffusion models: a feasibility study comparing the baseline and mid-treatment MRI examinations.
abstract: OBJECTIVE
  To assess the feasibility of the mono-exponential, bi-exponential and stretched-exponential models in evaluating response of breast tumours to neoadjuvant chemotherapy (NACT) at 3 T.
  
  
  METHODS
  Thirty-six female patients (median age 53, range 32-75 years) with invasive breast cancer undergoing NACT were enrolled for diffusion-weighted MRI (DW-MRI) prior to the start of treatment. For assessment of early response, changes in parameters were evaluated on mid-treatment MRI in 22 patients. DW-MRI was performed using eight b values (0, 30, 60, 90, 120, 300, 600, 900 s/mm2). Apparent diffusion coefficient (ADC), tissue diffusion coefficient (Dt), vascular fraction (ƒ), distributed diffusion coefficient (DDC) and alpha (α) parameters were derived. Then t tests compared the baseline and changes in parameters between response groups. Repeatability was assessed at inter- and intraobserver levels.
  
  
  RESULTS
  All patients underwent baseline MRI whereas 22 lesions were available at mid-treatment. At pretreatment, mean diffusion coefficients demonstrated significant differences between groups (p < 0.05). At mid-treatment, percentage increase in ADC and DDC showed significant differences between responders (49 % and 43 %) and non-responders (21 % and 32 %) (p = 0.03, p = 0.04). Overall, stretched-exponential parameters showed excellent repeatability.
  
  
  CONCLUSIONS
  DW-MRI is sensitive to baseline and early treatment changes in breast cancer using non-mono-exponential models, and the stretched-exponential model can potentially monitor such changes.
  
  
  CONCLUSIONS
  • Baseline diffusion coefficients demonstrated significant differences between complete pathological responders and non-responders. • Increase in ADC and DDC at mid-treatment can discriminate responders and non-responders. • The ƒ fraction at mid-treatment decreased in responders whereas increased in non-responders. • The mono- and stretched-exponential models showed excellent inter- and intrarater repeatability. • Treatment effects can potentially be assessed by non-mono-exponential diffusion models.
authors: Department of Radiology, School of Clinical Medicine, University of Cambridge, Box 218, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0QQ, UK.
authors: Reem
authors: http://orcid.org/0000-0002-0994-3756
authors: R
authors: Bedair
authors: Department of Radiology, Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge, CB2 0QQ, UK.
authors: Andrew N
authors: AN
authors: Priest
authors: Department of Radiology, Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge, CB2 0QQ, UK.
authors: Andrew J
authors: AJ
authors: Patterson
authors: Department of Radiology, Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge, CB2 0QQ, UK.|Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, CB2 0RE, UK.
authors: Mary A
authors: MA
authors: McLean
authors: Department of Radiology, School of Clinical Medicine, University of Cambridge, Box 218, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0QQ, UK.|Department of Radiology, Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge, CB2 0QQ, UK.
authors: Martin J
authors: MJ
authors: Graves
authors: Department of Radiology, School of Clinical Medicine, University of Cambridge, Box 218, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0QQ, UK.
authors: Roido
authors: R
authors: Manavaki
authors: Department of Radiology, School of Clinical Medicine, University of Cambridge, Box 218, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0QQ, UK.
authors: Andrew B
authors: AB
authors: Gill
authors: Department of Radiology, School of Clinical Medicine, University of Cambridge, Box 218, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0QQ, UK.
authors: Oshaani
authors: O
authors: Abeyakoon
authors: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, CB2 0RE, UK.
authors: John R
authors: JR
authors: Griffiths
authors: Department of Radiology, School of Clinical Medicine, University of Cambridge, Box 218, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0QQ, UK. fjg28@medschl.cam.ac.uk.
authors: Fiona J
authors: FJ
authors: Gilbert
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D038524:Diffusion Magnetic Resonance Imaging; D000077143:Docetaxel; D015251:Epirubicin / Q000008:administration & dosage; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D015203:Reproducibility of Results; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D015251:Epirubicin; D003520:Cyclophosphamide; D005472:Fluorouracil
keywords: Breast carcinoma; Diffusion-weighted MRI; Neoadjuvant treatment; Quantitative evaluation; Tumour biomarkers