Diffusion-weighted MRI Findings Predict Pathologic Response in Neoadjuvant Treatment of Breast Cancer: The ACRIN 6698 Multicenter Trial

Abstract

Purpose To determine if the change in tumor apparent diffusion coefficient (ADC) at diffusion-weighted (DW) MRI is predictive of pathologic complete response (pCR) to neoadjuvant chemotherapy for breast cancer. Materials and Methods In this prospective multicenter study, 272 consecutive women with breast cancer were enrolled at 10 institutions (from August 2012 to January 2015) and were randomized to treatment with 12 weekly doses of paclitaxel (with or without an experimental agent), followed by 12 weeks of treatment with four cycles of anthracycline. Each woman underwent breast DW MRI before treatment, at early treatment (3 weeks), at midtreatment (12 weeks), and after treatment. Percentage change in tumor ADC from that before treatment (ΔADC) was measured at each time point. Performance for predicting pCR was assessed by using the area under the receiver operating characteristic curve (AUC) for the overall cohort and according to tumor hormone receptor (HR)/human epidermal growth factor receptor 2 (HER2) disease subtype. Results The final analysis included 242 patients with evaluable serial imaging data, with a mean age of 48 years ± 10 (standard deviation); 99 patients had HR-positive (hereafter, HR+)/HER2-negative (hereafter, HER2-) disease, 77 patients had HR-/HER2- disease, 42 patients had HR+/HER2+ disease, and 24 patients had HR-/HER2+ disease. Eighty (33%) of 242 patients experienced pCR. Overall, ΔADC was moderately predictive of pCR at midtreatment/12 weeks (AUC = 0.60; 95% confidence interval [CI]: 0.52, 0.68; P = .017) and after treatment (AUC = 0.61; 95% CI: 0.52, 0.69; P = .013). Across the four disease subtypes, midtreatment ΔADC was predictive only for HR+/HER2- tumors (AUC = 0.76; 95% CI: 0.62, 0.89; P < .001). In a test subset, a model combining tumor subtype and midtreatment ΔADC improved predictive performance (AUC = 0.72; 95% CI: 0.61, 0.83) over ΔADC alone (AUC = 0.57; 95% CI: 0.44, 0.70; P = .032.). Conclusion After 12 weeks of therapy, change in breast tumor apparent diffusion coefficient at MRI predicts complete pathologic response to neoadjuvant chemotherapy. © RSNA, 2018 Online supplemental material is available for this article.

Test–retest repeatability and reproducibility of ADC measures by breast DWI: Results from the ACRIN 6698 trial

“…Previous studies in patients undergoing NAC have reported significant changes in tumor ADC with treatment response, with effect sizes generally large compared with our repeatability value of wCV = 4.8%. Responders exhibited tumor ADC increases ranging from 9% to over 60% in the prior studies, depending on treatment timepoint …”

“…The primary MRI technique for assessing breast cancer is dynamic contrast‐enhanced (DCE) imaging, which characterizes tissue vascularity. However, growing evidence supports diffusion‐weighted imaging (DWI), a functional imaging technique reflecting water diffusion properties in tissue, as a supplemental and/or alternative technique to DCE . Specifically, the apparent diffusion coefficient (ADC) measured by DWI reflects water mobility impeded by cellular constituents and interstitial tortuosity, and it has shown promise as an imaging biomarker to measure early tumor response to cytotoxic treatment …”

Additive value of diffusion‐weighted MRI in the I‐SPY 2 TRIAL

“…In previously published results of the ACRIN 6698, the authors explored the combination of ADC, FTV, and HR/HER2 subtype at mid‐NAC. A model combining percentage change in ADC, percentage change in FTV, and cancer subtype resulted in an AUC of 0.71.…”

“…The ACRIN (American College of Radiology Imaging Network) 6698 trial, a substudy of I‐SPY 2, evaluated the change in tumor ADC for predicting pCR. The trial found that after 12 weeks of therapy (between drug regimens), the percentage change in tumor ADC predicts pCR . Their study also showed that ADC achieved higher predictive performance in hormone receptor (HR)‐positive and human epidermal growth factor receptor 2 (HER2)‐negative cancer than other cancer subtypes.…”

MRI does not predict pathologic complete response after neoadjuvant chemotherapy for breast cancer

“…Functional tumor volume, a computer estimate of volume using a signal enhancement ratio method (signal intensities on pre‐ vs post‐contrast images), was shown to be associated with recurrence‐free survival. Partridge et al, reporting on diffusion‐weighted MRI performance for 242 I‐SPY 2 patients enrolled in ACRIN 6698, observed that combining tumor molecular subtype with changes in the mid‐treatment apparent diffusion coefficient were moderately predictive of pCR (area under the curve = 0.72; 95% confidence interval [CI]: 0.61, 0.83).…”