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.