Multiparametric MRI for Early Response Assessment in Early-Stage Breast Cancer Treated with Single-Fraction Neoadjuvant Radiotherapy: A Single-Institution Feasibility Study

Purpose Single-fraction neoadjuvant radiotherapy (SF-NRT) is a promising alternative for patients with low-risk, early-stage breast cancer. However, the optimal post-treatment interval for assessing response remains largely undefined. This study evaluated the feasibility of multiparametric MRI (mp-MRI) for detecting early biological changes after SF-NRT within the arm Magnetic Resonance Image Guided Single Fraction Preoperative Radiotherapy for Early Breast Cancer (RICE) feasibility trial. Methods Nine postmenopausal women (median age 69 years) with ER/PR-positive, grade 1–2 invasive ductal carcinoma ≤ 20 mm underwent a single 21 Gy preoperative fraction on the Elekta Unity 1.5 T MR-linac. MRI (1.5 T Philips Ingenia Ambition) was performed at baseline and five weeks post-treatment. Imaging included diffusion-weighted (ADC), standard DCE-MRI with voxel-wise signal enhancement ratio (SER) mapping, and ultrafast DCE analysis. Pathologic response was classified using the modified Miller–Payne system. Results Six patients (67%) demonstrated partial pathologic response and three (33%) were non-responders; none achieved pathologic complete response (pCR). Across all patients, ADC increased (0.99 × 10⁻³ to 1.18 × 10⁻³ mm²/s), with partial responders showing greater percentage rises compared to non responders (+ 44.5% vs + 11.1%). SER habitat analysis revealed decreased washout and intermediate-enhancing voxels and a decline in peak SER (0.98 to 0.83), consistent with reduced perfusion heterogeneity. Tumor morphological analysis and ultrafast parameters displayed minimal differences and large inter-patient variability. Conclusions mp-MRI demonstrated biologically plausible diffusion and perfusion changes at five weeks following SF-NRT, with directional differences between response groups preceding measurable morphologic regression. These exploratory findings require validation in larger cohorts. Trial registration This trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR). Registered 31st of May 2021. Registration number: ACTRN12621000659808.