Impact of Alternate b-Value Combinations and Metrics on the Predictive Performance and Repeatability of Diffusion-Weighted MRI in Breast Cancer Treatment: Results from the ECOG-ACRIN A6698 Trial

In diffusion-weighted MRI (DW-MRI), choice of b-value influences apparent diffusion coefficient (ADC) values by probing different aspects of the tissue microenvironment. As a secondary analysis of the multicenter ECOG-ACRIN A6698 trial, the purpose of this study was to investigate the impact of alternate b-value combinations on the performance and repeatability of tumor ADC as a predictive marker of breast cancer treatment response. The final analysis included 210 women who underwent standardized 4-b-value DW-MRI (b = 0/100/600/800 s/mm(2)) at multiple timepoints during neoadjuvant chemotherapy treatment and a subset (n = 71) who underwent test-retest scans. Centralized tumor ADC and perfusion fraction (f(p)) measures were performed using variable b-value combinations. Prediction of pathologic complete response (pCR) based on the mid-treatment/12-week percent change in each metric was estimated by area under the receiver operating characteristic curve (AUC). Repeatability was estimated by within-subject coefficient of variation (wCV). Results show that two-b-value ADC calculations provided non-inferior predictive value to four-b-value ADC calculations overall (AUCs = 0.60-0.61 versus AUC = 0.60) and for HR+/HER2- cancers where ADC was most predictive (AUCs = 0.75-0.78 versus AUC = 0.76), p < 0.05. Using two b-values (0/600 or 0/800 s/mm(2)) did not reduce ADC repeatability over the four-b-value calculation (wCVs = 4.9-5.2% versus 5.4%). The alternate metrics ADC(fast) (b <= 100 s/mm(2)), ADC(slow) (b >= 100 s/mm(2)), and f(p) did not improve predictive performance (AUCs = 0.54-0.60, p = 0.08-0.81), and ADC(fast) and f(p) demonstrated the lowest repeatability (wCVs = 6.71% and 12.4%, respectively). In conclusion, breast tumor ADC calculated using a simple two-b-value approach can provide comparable predictive value and repeatability to full four-b-value measurements as a marker of treatment response.