Incremental Value of Synthetic MRI Radiomics in Predicting Neoadjuvant Response in Human Epidermal Growth Factor...

Purpose To evaluate the added value of a synthetic radiomics model (S-Radiomics) that integrates topologic and Hessian-based features with traditional radiomic features for predicting a pathologic complete response (pCR) in human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Materials and Methods Patients with HER2-positive breast cancer from three centers were retrospectively included between January 2018 and January 2024. Patients from centers 1 and 2 (n = 201) were randomly assigned to training (n = 150) and internal testing (n = 51) sets, whereas patients from center 3 (n = 82) constituted external testing set I. An additional genomic set (n = 64, I-SPY 2) and external testing set II (n = 57, I-SPY 1) were used for independent validation. Multivariable logistic regression with all clinical variables was used to identify independent predictors (P < .05) and develop the clinical model, adjusting for potential confounders. Traditional radiomics model (T-Radiomics) and S-Radiomics were constructed. Performance was evaluated using area under the receiver operating characteristic curve (AUC), integrated discrimination improvement, net reclassification index, and survival analysis. Results A total of 404 female patients with HER2-positive breast cancer (mean age ± SD, 50 years ± 9) were included. The S-Radiomics outperformed the T-Radiomics on both the internal (AUC, 0.86 vs 0.78; P = .37) and external test (AUC, 0.84 vs 0.73; P = .11) sets, with improvements in the integrated discrimination improvement (P = .24 and .01) and net reclassification index (P = .21 and .01). Shapley additive explanations analysis revealed topologic features as the most important predictors. For center 1, survival analysis revealed longer disease-free survival in predicted responders (P = .02). Conclusion The S-Radiomics outperformed the T-Radiomics in predicting pathologic complete responses in patients with HER2-positive breast cancer. Keywords: Radiogenomics, MRI, Breast, Human Epidermal Growth Factor Receptor 2, Breast Cancer, Neoadjuvant Chemotherapy, Pathologic Complete Response, Radiomics Supplemental material is available for this article. © RSNA, 2026.