title: Role of dynamic contrast enhanced MRI in monitoring early response of locally advanced breast cancer to neoadjuvant chemotherapy.
abstract: Neoadjuvant chemotherapy has become the standard treatment for patients with locally advanced breast cancer; however a technique that can accurately differentiate responders from non-responders at an early time point during treatment has still to be identified. The purpose of this work was to evaluate the ability of pharmacokinetically modelled dynamic contrast-enhanced MRI data to predict and monitor response of patients diagnosed with locally advanced breast cancer to neoadjuvant chemotherapy, at an early time point during treatment. Sixty-eight patients with histology proven breast cancer underwent MRI examination prior to treatment, early during treatment and following the final cycle of chemotherapy. A two compartment pharmacokinetic model provided the kinetic parameters transfer constant (Ktrans), rate constant (Kep) and extracellular extravascular space (Ve) for a region of interest encompassing the whole lesion (ROIwhole) and a 3x3 pixel 'hot-spot' showing the greatest mean maximum percentage enhancement from within that region (ROIhs). Following treatment 48 patients were classified as responders and 20 as non-responders based on total tumour volume reduction. Tumour volume changes between the pre-treatment and early treatment time points demonstrated differences between responders and non-responders with percentage change revealing the most significant result (p<0.001). Analysis based on ROIhs provided more statistically significant differences between responders and non-responders then ROIwhole analysis. ROIhs analysis demonstrated differences between responders and non-responders both prior to and early during treatment. A highly significant reduction in both Ktrans and Kep (p<0.001) was noted for responders between the pre-treatment and early treatment time points, while Ve significantly increased during the same time period for non-responders (p<0.001). Quantification of dynamic contrast enhancement parameters provides a potential means for differentiating responders from non-responders early during their treatment, thereby allowing a prompt change in treatment if necessary.
authors.affiliation: Post-graduate Medical School, Division of Cancer, Centre for Magnetic Resonance Investigations, University of Hull, UK. m.d.pickles@medschool.hull.ac.uk
authors.forename: Martin D
authors.initials: MD
authors.lastname: Pickles
authors.forename: Martin
authors.initials: M
authors.lastname: Lowry
authors.forename: David J
authors.initials: DJ
authors.lastname: Manton
authors.forename: Peter
authors.initials: P
authors.lastname: Gibbs
authors.forename: Lindsay W
authors.initials: LW
authors.lastname: Turnbull
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D017024:Chemotherapy, Adjuvant; D003287:Contrast Media / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D003287:Contrast Media; D015251:Epirubicin; D003520:Cyclophosphamide; D005472:Fluorouracil