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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/mm2) at multiple timepoints during neoadjuvant chemotherapy treatment and a subset (n = 71) who underwent test–retest scans. Centralized tumor ADC and perfusion fraction (fp) 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 &lt; 0.05. Using two b-values (0/600 or 0/800 s/mm2) did not reduce ADC repeatability over the four-b-value calculation (wCVs = 4.9–5.2% versus 5.4%). The alternate metrics ADCfast (b ≤ 100 s/mm2), ADCslow (b ≥ 100 s/mm2), and fp did not improve predictive performance (AUCs = 0.54–0.60, p = 0.08–0.81), and ADCfast and fp 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.

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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