Development and validation of an MRI spatiotemporal interaction model for early noninvasive prediction of neoadjuvant chemotherapy response in breast cancer: a multicentre study

Background: The accurate and early evaluation of response to neoadjuvant chemotherapy (NAC) in breast cancer is crucial for optimizing treatment strategies and minimizing unnecessary interventions. While deep learning (DL)-based approaches have shown promise in medical imaging analysis, existing models often fail to comprehensively integrate spatial and temporal tumor dynamics. This study aims to develop and validate a spatiotemporal interaction (STI) model based on longitudinal MRI data to predict pathological complete response (pCR) to NAC in breast cancer patients. Methods: This study included retrospective and prospective datasets from five medical centers in China, collected from June 2018 to December 2024. These datasets were assigned to the primary cohort (including training and internal validation sets), external validation cohorts, and a prospective validation cohort. DCE-MRI scans from both pre-NAC (T0) and early-NAC (T1) stages were collected for each patient, along with surgical pathology results. A Siamese network-based STI model was developed, integrating spatial features from tumor segmentation with temporal dependencies using a transformer-based multi-head attention mechanism. This model was designed to simultaneously capture spatial heterogeneity and temporal dynamics, enabling accurate prediction of NAC response. The STI model's performance was evaluated using the area under the ROC curve (AUC) and Precision-Recall curve (AP), accuracy, sensitivity, and specificity. Additionally, the I-SPY1 and I-SPY2 datasets were used for Kaplan-Meier survival analysis and to explore the biological basis of the STI model, respectively. The prospective cohort was registered with Chinese Clinical Trial Registration Centre (ChiCTR2500102170). Findings: A total of 1044 patients were included in this study, with the pCR rate ranging from 23.8% to 35.9%. The STI model demonstrated good performance in early prediction of NAC response in breast cancer. In the external validation cohorts, the AUC values were 0.923 (95% CI: 0.859-0.987), 0.892 (95% CI: 0.821-0.963), and 0.913 (95% CI: 0.835-0.991), all outperforming the single-timepoint T0 or T1 models, as well as models with spatial information added (all p < 0.05, Delong test). Additionally, the STI model significantly outperformed the clinical model (p < 0.05, Delong test) and radiologists' predictions. In the prospective validation cohort, the STI model identified 90.2% (37/41) of non-pCR and 82.6% (19/23) of pCR patients, reducing misclassification rates by 58.7% and 63.3% compared to radiologists. This indicates that these patients might benefit from treatment adjustment or continued therapy in the early NAC stage. Survival analysis showed a significant correlation between the STI model and both recurrence-free survival (RFS) and overall survival (OS) in breast cancer patients. Further investigation revealed that favorable NAC responses predicted by the STI model were closely linked to upregulated immune-related genes and enhanced immune cell infiltration. Interpretation: Our study established a novel noninvasive STI model that integrates the spatiotemporal evolution of MRI before and during NAC to achieve early and accurate pCR prediction, offering potential guidance for personalized treatment. Funding: This study was supported by the National Natural Science Foundation of China (82302314, 62271448, 82171920, 81901711), Basic and Applied Basic Research Foundation of Guangdong Province (2022A1515110792, 2023A1515220097, 2024A1515010653), Medical Scientific Research Foundation of Guangdong Province (A2023073, A2024116), Science and Technology Projects in Guangzhou (2023A04J1275, 2024A03J1030, 2025A03J4163, 2025A03J4162); Guangzhou First People's Hospital Frontier Medical Technology Project (QY-C04).