Early Prediction and Evaluation of Breast Cancer Response to Neoadjuvant Chemotherapy Using Quantitative DCE-MRI

Abstract

The purpose is to compare quantitative dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) metrics with imaging tumor size for early prediction of breast cancer response to neoadjuvant chemotherapy (NACT) and evaluation of residual cancer burden (RCB). Twenty-eight patients with 29 primary breast tumors underwent DCE-MRI exams before, after one cycle of, at midpoint of, and after NACT. MRI tumor size in the longest diameter (LD) was measured according to the RECIST (Response Evaluation Criteria In Solid Tumors) guidelines. Pharmacokinetic analyses of DCE-MRI data were performed with the standard Tofts and Shutter-Speed models (TM and SSM). After one NACT cycle the percent changes of DCE-MRI parameters Ktrans (contrast agent plasma/interstitium transfer rate constant), ve (extravascular and extracellular volume fraction), kep (intravasation rate constant), and SSM-unique τi (mean intracellular water lifetime) are good to excellent early predictors of pathologic complete response (pCR) vs. non-pCR, with univariate logistic regression C statistics value in the range of 0.804 to 0.967. ve values after one cycle and at NACT midpoint are also good predictors of response, with C ranging 0.845 to 0.897. However, RECIST LD changes are poor predictors with C = 0.609 and 0.673, respectively. Post-NACT Ktrans, τi, and RECIST LD show statistically significant (P < .05) correlations with RCB. The performances of TM and SSM analyses for early prediction of response and RCB evaluation are comparable. In conclusion, quantitative DCE-MRI parameters are superior to imaging tumor size for early prediction of therapy response. Both TM and SSM analyses are effective for therapy response evaluation. However, the τi parameter derived only with SSM analysis allows the unique opportunity to potentially quantify therapy-induced changes in tumor energetic metabolism.

Dynamic Contrast-Enhanced MRI–Derived Intracellular Water Lifetime (τi): A Prognostic Marker for Patients with Head and Neck Squamous Cell Carcinomas

“…The inverse correlation between τ i and tumor metabolism was corroborated when higher τ i was observed in complete-responders compared to poor-responders with breast carcinomas. 12, 14 Taken together these studies imply that malignant cells from tumors with high τ i have reduced metabolic energy available for their growth, relative to malignant cells from tumors with low τ i .…”

“…12 The unique strength of τ i lies in the fact that it is less sensitive to AIF scaling variations than K trans 13 indicating that τ i is a more reproducible and reliable marker. The parameter τ i has been used to characterize breast, 14 prostate, 15, 16 esophageal 17 and hepatocellular cancer. 18 A recent study 19 also demonstrated the prognostic utility of τ i in predicting survival in patients with hepatocellular carcinomas.…”

Evaluation of Soft Tissue Sarcoma Response to Preoperative Chemoradiotherapy Using Dynamic Contrast-Enhanced Magnetic Resonance Imaging

“…For quantification of the pre-CA T 1 value, T 10 , proton density- weighted images were acquired immediately before and spatially coregistered with the DCE-MRI scan (22, 23). The data acquisition pulse sequence and parameters were the same as those for the DCE-MRI scan except for flip angle = 5° and repetition time = 50 milliseconds.…”

“…For each DCE-MRI data set, the voxel signal intensity time-courses within the multisection tumor ROIs were subjected to pharmacokinetic analysis using a 2-compartment 3-parameter fast exchange regime (FXR)-allowed version of the Shutter- Speed model (SSM) (18, 19, 23). The 3 fitting parameters of the FXR-SSM are K trans (rate constant for plasma/interstitium CA transfer), v e (volume fraction of extravascular and extracellular space), and τ i (mean intracellular water molecule lifetime).…”

Imaging Considerations and Interprofessional Opportunities in the Care of Breast Cancer Patients in the Neoadjuvant Setting

“…39,78 Furthermore, when quantitative pharmacokinetic DCE-MRI is performed following one cycle of NAT, parameters were shown to be excellent predictors of pCR prior to any significant changes in RECIST criteria. 45,46 Figure 1 reveals how quantitative DCE-MRI parameter, k ep , can show early response during NAT.…”