Abstract

Abstract Introduction: Dynamic contrast-enhanced MRI (DCE) is currently used to evaluate neoadjuvant therapy response of breast cancer (1). However, DCE requires expert radiologist readers to assess the change in longest tumor dimension during therapy, as well as administration of Gadolinium contrast agents. One MRI modality that does not require contrast agents is diffusion-weighted MRI (DWI), a method that detects the microscopic diffusion of water molecules. However, the commonly used DWI method apparent diffusion coefficient (ADC) is not fully optimised in the breast (2). The purpose of the current study was to evaluate the recent DWI method Restriction Spectrum Imaging (RSI) (2) to automatically monitor breast tumor size during neoadjuvant therapy. Methods: Twenty-seven women underwent 3T MRI at four time points during therapy at University of California San Diego; 17 received all four scans (see Table 1 for patient details). Inclusion criteria included biopsy-proven unilateral invasive breast cancer ≥2.5 cm (defined on clinical examination/imaging) with indication for neoadjuvant therapy. The therapy used was primarily paclitaxel (+/-experimental agent) followed by anthracycline. The MRI protocol included Gadolinium DCE and DWI (b-values 0, 500, 1500, 4000 s/mm2); TE/TR = 82/9000 ms. ADC was calculated using b-values < 1000 s/mm2 while signal from all available b-values were fitted to the previously-developed three-component RSI model (2). The tumor size by RSI was assessed against manual DCE tumor size and mean ADC values. Prediction of therapy response during therapy and residual tumor post-therapy were assessed using non-pathological complete response (non-pCR) as endpoint. pCR was defined as ypT0/is or ypN0. Results: Ten patients experienced pCR. Prediction of non-pCR by ROC AUC at the early-therapy time point was 0.65 for RSI, 0.64 for DCE and 0.45 for ADC (Table 2). Prediction of post-therapy residual tumor is given in Table 3. Discussion: The novel RSI cancer tissue classifier predicted response to neoadjuvant therapy after only 19 days. RSI could also identify 71% of cases with residual tumor at surgery with 90% specificity post-therapy. RSI performance was similar to performance by standard MRI by manual tumor measurement on DCE. In contrast to standard-of-care MRI by using DCE and ADC that requires manual user input, the RSI classifier is automatic. This suggests that RSI may aid to cost-efficiently evaluate neoadjuvant therapy of breast cancer, with the aim to help guide clinical decision-making and enable tailored therapy regimens.

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