Diffusion-Weighted MRI for Predicting Pathologic Complete Response in Neoadjuvant Immunotherapy

Li W, Le NN, Onishi N, Newitt DC, Wilmes LJ, Gibbs JE, Carmona-Bozo J, Liang J, Partridge SC, Price ER, Joe BN, Kornak J, Magbanua MJM, Nanda R, LeStage B, Esserman LJ, I-SPY Imaging Working Group, I-SPY Investigator Network, van’t Veer LJ, Hylton NM

Immunotherapy targets patients’ immune systems to fight cancer. The aim of this retrospective study is to assess tumor response to pre-operative immunotherapy and predict pathologic complete response using MRI at an early treatment time- point. Based on our analysis with a cohort from the multi-center I-SPY 2 clinical trial, we found diffusion-weighted MRI is superior to dynamic contrast-enhanced MRI, where the latter is a standard and most-commonly used MRI modality, in assessing immunotherapy, while no significant difference was observed in the control cohort where only standard chemotherapy was provided. This study tested the hypothesis that a change in the apparent diffusion coefficient (ADC) measured in diffusion-weighted MRI (DWI) is an independent imaging marker, and ADC performs better than functional tumor volume (FTV) for assessing treatment response in patients with locally advanced breast cancer receiving neoadjuvant immunotherapy. A total of 249 patients were randomized to standard neoadjuvant chemotherapy with pembrolizumab (pembro) or without pembrolizumab (control). DCE-MRI and DWI, performed prior to and 3 weeks after the start of treatment, were analyzed. Percent changes of tumor ADC metrics (mean, 5th to 95th percentiles of ADC histogram) and FTV were evaluated for the prediction of pathologic complete response (pCR) using a logistic regression model. The area under the ROC curve (AUC) estimated for the percent change in mean ADC was higher in the pembro cohort (0.73, 95% confidence interval [CI]: 0.52 to 0.93) than in the control cohort (0.63, 95% CI: 0.43 to 0.83). In the control cohort, the percent change of the 95th percentile ADC achieved the highest AUC, 0.69 (95% CI: 0.52 to 0.85). In the pembro cohort, the percent change of the 25th percentile ADC achieved the highest AUC, 0.75 (95% CI: 0.55 to 0.95). AUCs estimated for percent change of FTV were 0.61 (95% CI: 0.39 to 0.83) and 0.66 (95% CI: 0.47 to 0.85) for the pembro and control cohorts, respectively. Tumor ADC may perform better than FTV to predict pCR at an early treatment time-point during neoadjuvant immunotherapy.

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