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

Abstract

Background The change in apparent diffusion coefficient (ADC) measured from diffusion‐weighted imaging (DWI) has been shown to be predictive of pathologic complete response (pCR) for patients with locally invasive breast cancer undergoing neoadjuvant chemotherapy. Purpose To investigate the additive value of tumor ADC in a multicenter clinical trial setting. Study Type Retrospective analysis of multicenter prospective data. Population In all, 415 patients who enrolled in the I‐SPY 2 TRIAL from 2010 to 2014 were included. Field Strength/Sequence 1.5T or 3T MRI system using a fat‐suppressed single‐shot echo planar imaging sequence with b‐values of 0 and 800 s/mm2 for DWI, followed by a T1‐weighted sequence for dynamic contrast‐enhanced MRI (DCE‐MRI) performed at pre‐NAC (T0), after 3 weeks of NAC (T1), mid‐NAC (T2), and post‐NAC (T3). Assessment Functional tumor volume and tumor ADC were measured at each MRI exam; pCR measured at surgery was assessed as the binary outcome. Breast cancer subtype was defined by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status. Statistical Tests A logistic regression model was used to evaluate associations between MRI predictors with pCR. The cross‐validated area under the curve (AUC) was calculated to assess the predictive performance of the model with and without ADC. Results In all, 354 patients (128 HR+/HER2–, 60 HR+/HER2+, 34 HR–/HER2+, 132 HR–/HER2–) were included in the analysis. In the full cohort, adding ADC predictors increased the AUC from 0.76 to 0.78 at mid‐NAC and from 0.76 to 0.81 at post‐NAC. In HR/HER2 subtypes, the AUC increased from 0.52 to 0.65 at pre‐NAC for HR+/HER2–, from 0.67 to 0.73 at mid‐NAC and from 0.72 to 0.76 at post‐NAC for HR+/HER2+, from 0.71 to 0.81 at post‐NAC for triple negatives. Data Conclusion The addition of ADC to standard functional tumor volume MRI showed improvement in the prediction of treatment response in HR+ and triple‐negative breast cancer. Level of Evidence: 2 Technical Efficacy Stage: 4 J. Magn. Reson. Imaging 2019;50:1742–1753.

Circulating tumor DNA in neoadjuvant-treated breast cancer reflects response and survival

“…In summary, our study shows promise that early response prediction by highly sensitive ctDNA analysis in high-risk early breast cancer patients may facilitate a timely and judicious change in treatment to improve patients' chances of achieving favorable long-term outcomes. The I-SPY 2 TRIAL provides an excellent platform to investigate how personalized ctDNA testing can complement imaging [51] and pathologic evaluation [52] of tumor response to fine-tune pCR as a surrogate endpoint for improved survival.…”

Current Landscape of Breast Cancer Imaging and Potential Quantitative Imaging Markers of Response in ER-Positive Breast Cancers Treated with Neoadjuvant Therapy

“…When ∆ADC was combined with RECIST as predictors, further improvement in the prediction was observed in all subtypes. The additive value of ∆ADC as a covariate with the FTV metric was observed in the I-SPY 2 TRIAL with a subset of 354 patients [123]. Interestingly, while prediction improvements were found by adding ∆ADCs to the optimized FTV model at mid-treatment or post-NAC for HR+/HER2+ and TN tumors, significant improvement in predicting the HR+/HER2− subtype was found by combining pre-treatment ADC with the optimized FTV model.…”

“…patients [123]. Interestingly, while prediction improvements were found by adding ∆ADCs to the optimized FTV model at mid-treatment or post-NAC for HR+/HER2+ and TN tumors, significant improvement in predicting the HR+/HER2− subtype was found by combining pre-treatment ADC with the optimized FTV model.…”

Role of MRI to Assess Response to Neoadjuvant Therapy for Breast Cancer

“…improved prediction of treatment response by 2-13%, depending on the timepoint and cancer subtype. 88 A metaanalysis of DWI studies notes a lack of consensus on the appropriate b value to use, 83 but we note that b values of 0 and 800 s/mm 2 are most commonly used in the literature. Higher b values may increase the specificity of DWI and result in a lower signal-to-noise ratio.…”