Dynamic Contrast-Enhanced MRI as a Predictor of Patient Outcome with Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer.
Authors: S. Li, A. Padhani, N. Taylor, M. Ah-See, M. Beresford, J. Stirling, D. Stott, D. Collins, J. d'Arcy, A. Makris
Journal: Cancer Research (2009)

Abstract Background: Early kinetic changes in DCE-MRI are predictive of clinical and pathologic response to neoadjuvant chemotherapy (NAC) in primary breast cancer (BC). Baseline vascular parameters and changes in these parameters with NAC have not been previously correlated with disease-free survival (DFS) and overall survival (OS) in BC.Methods: 73 patients (median age 45, range 26-70) with locally advanced BC due to undergo 4-6 cycles of anthracycline and/or taxotere NAC were imaged with DCE-MRI before and after 2 cycles as part of 2 prospective studies. Quantitative and semi-quantitative kinetic parameters such as Ktrans (inflow transfer constant) and IAUGC60 (initial area under the gadolinium-time curve) were derived from whole tumour regions of interest. Values for both baseline and changes in kinetic parameters as well as known prognostic indicators including age, grade, tumour size, nodal, hormonal and HER2 receptor status, and pathologic complete response were then correlated with DFS and OS using Kaplan-Meier analysis (log-rank test) and the Cox proportional hazards model. Median values for Ktrans and IAUGC60 were used to dichotomise data for survival analysis.Results: DCE-MRIs were performed in 62 patients before treatment (baseline group) and in 56 patients after 2 cycles of NAC. 3 were found to have metastatic disease after enrolment, 8 were not able to undergo both MRIs, 4 did not undergo their second MRI and in 2, the second scan was performed after 3 cycles of NAC. The median follow-up time for DFS was 33.7 months (range 0.3-75.6) and for OS 44.4 months (range 7.6-84.7). There were 21 distant recurrences in the baseline group (3 also had additional local recurrence) and 19 distant recurrences amongst those who were imaged pre and post treatment (2 also had local recurrence). There were 14 deaths in total (13 from BC, 1 from an unknown cause). Baseline DCE-MRI vascular parameters were not significantly associated with DFS or OS.Univariate analysis (n=56) using Cox regression showed age and ER positivity to be significant predictors of DFS &amp; a trend towards a longer DFS with greater reductions in Ktrans (HR 1.94, 95%CI 0.73-5.18; p=0.186) and in IAUGC60 (HR 1.98, 95%CI 0.74-5.28; p=0.172). Multivariate analysis for DFS demonstrated that changes in Ktrans (HR 2.18, 95%CI 0.79-6.05; p=0.133) and IAUGC60 (HR 2.11, 95%CI 0.78-5.74; p=0.142) remain potential prognostic indicators although results did not reach statistical significance. Both age and ER positivity were independent prognostic variables. Changes in DCE-MRI vascular parameters did not predict for OS.Conclusions: These results suggest that changes in DCE-MRI vascular parameters with reductions in Ktrans and IAUGC60, are associated with lower recurrence rates and could be potential prognostic biomarkers for DFS. A larger cohort is currently being studied to explore this further. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1092.