Multi-Site Clinical Evaluation of DW-MRI as a Treatment Response Metric for Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy

Abstract

PurposeTo evaluate diffusion weighted MRI (DW-MR) as a response metric for assessment of neoadjuvant chemotherapy (NAC) in patients with primary breast cancer using prospective multi-center trials which provided MR scans along with clinical outcome information.Materials and MethodsA total of 39 patients with locally advanced breast cancer accrued from three different prospective clinical trials underwent DW-MR examination prior to and at 3–7 days (Hull University), 8–11 days (University of Michigan) and 35 days (NeoCOMICE) post-treatment initiation. Thirteen patients, 12 of which participated in treatment response study, from UM underwent short interval (<1hr) MRI examinations, referred to as “test-retest” for examination of repeatability. To further evaluate stability in ADC measurements, a thermally controlled diffusion phantom was used to assess repeatability of diffusion measurements. MRI sequences included contrast-enhanced T1-weighted, when appropriate, and DW images acquired at b-values of 0 and 800 s/mm2. Histogram analysis and a voxel-based analytical technique, the Parametric Response Map (PRM), were used to derive diffusion response metrics for assessment of treatment response prediction.ResultsMean tumor apparent diffusion coefficient (ADC) values generated from patient test-retest examinations were found to be very reproducible (|ΔADC|<0.1x10-3mm2/s). This data was used to calculate the 95% CI from the linear fit of tumor voxel ADC pairs of co-registered examinations (±0.45x10-3mm2/s) for PRM analysis of treatment response. Receiver operating characteristic analysis identified the PRM metric to be predictive of outcome at the 8–11 (AUC = 0.964, p = 0.01) and 35 day (AUC = 0.770, p = 0.05) time points (p<.05) while whole-tumor ADC changes where significant at the later 35 day time interval (AUC = 0.825, p = 0.02).ConclusionThis study demonstrates the feasibility of performing a prospective analysis of DW-MRI as a predictive biomarker of NAC in breast cancer patients. In addition, we provide experimental evidence supporting the use of sensitive analytical tools, such as PRM, for evaluating ADC measurements.

DWI in the Assessment of Breast Lesions

“…Such cytotoxic changes precede changes in tumor size or perfusion, suggesting DWI has potential to provide early indication of treatment efficacy. In support of this theory, a growing number of clinical studies have demonstrated that treatment-induced changes in breast tumor ADC values can differentiate responders and non-responders early in the course of treatment, after only the first cycle of chemotherapy [42–44], Figure 4.…”

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

“…38,39 A multisite trial found that increased ADC observed early in the course of NAT is predictive of response. 40 These changes are better predictors of eventual pathological tumor response to therapy than measurements of tumor diameter or volume. 41 Furthermore, breast cancer patients with lower ADC prior to the initiation of NAT were more likely to exhibit a decrease in tumor volume during treatment.…”

Variability and bias assessment in breast ADC measurement across multiple systems

“…Quality control is much needed to ensure accurate quantitation of diffusion-weighted MRI (DWI) measurements for clinical assessments (4), the importance of which is further substantiated by the bias in diffusion measurements recently observed in a multicenter trial (7). Similarly, Min et al summarized several studies that determine a threshold ADC value between benign and malignant breast tumors (8): the reported thresholds ranged from 0.85 × 10 −3 m 2 /s to 1.48 × 10 −3 m 2 /s, which is too broad to be used clinically.…”