We greatly appreciated the insightful commentary by Dr Nandita M. deSouza (1) on our recent article reporting results of American College of Radiology Imaging Network (ACRIN) trial 6698, a multicenter trial investigating diffusion-weighted (DW) MRI for monitoring breast cancer response to therapy (2). Dr deSouza accurately described a number of important challenges and pitfalls of implementing DW MRI in multicenter trials and in utilizing the apparent diffusion coefficient (ADC) as an imaging biomarker to monitor therapy, in particular emphasizing the need for rigorous quality control and standardization measures (1).

Specifically, Dr deSouza stated: “The inclusion of test-retest studies in multicenter trials using quantitative imaging biomarkers is invaluable….The use of a test-retest approach in the I-SPY 2 trial would have confirmed the validity of the ADC changes….” and “The I-SPY 2 [Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular Analysis 2] trial has been a marathon multicenter undertaking….However, future trials must incorporate rigorous quality assurance, quality control, and reproducibility measures to both data acquisition and processing when treatment decisions are proposed based on interpretation of quantified parameter changes such as ADC.”

We heartily agree and would therefore like to respectfully point out that the ACRIN 6698 trial did in fact include a secondary aim to perform a test-retest ADC repeatability substudy. We regret that space limitations did not allow us to include this information along with the primary analysis in our article, and so Dr deSouza was not aware of the test-retest study at the time of her commentary. However, we have since published the ACRIN 6698 test-retest study results (3) and would like to make the readers aware of that additional information, which may be helpful for interpreting results of the study and in planning future trials incorporating quantitative breast DW imaging. In the ACRIN 6698 test-retest study, a coffee-break design was used to assess variability between repeat DW images, and both intra- and interreader agreement in tumor ADC quantitation were assessed. Overall, the results showed that excellent repeatability and reproducibility of breast tumor ADC measures could be achieved in a multi-institution setting using a standardized protocol and quality assurance procedure, but also supported the need for ongoing quality control methods to ensure consistent image quality and reduce data loss.

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