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).

Purpose

To evaluate changes in tumor microvasculature induced by bevacizumab and the usefulness of these changes predicting response to further neoadjuvant therapy.

Material and 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, K_ep, V_e, 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%), K_ep (−38%), V_e (−11%), and AUC₉₀ (−44%) and ROI 2 K^trans (−43%), K_ep (−39%), V_e (−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.

Conclusion

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.