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Objectives: We evaluate the feasibility of treatment response prediction using MRI-based pre-, post-, and delta-radiomic features for locally advanced rectal cancer (LARC) patients treated by neoadjuvant chemoradiation therapy (nCRT). Materials and Methods: This retrospective study included 53 LARC patients divided into a training set (Center#1, n = 36) and external validation set (Center#2, n = 17). T2-weighted (T2W) MRI was acquired for all patients, 2 weeks before and 4 weeks after nCRT. Ninety-six radiomic features, including intensity, morphological and second-and high-order texture features were extracted from segmented 3D volumes from T2W MRI. All features were harmonized using ComBat algorithm. Max-Relevance-Min-Redundancy (MRMR) algorithm was used as feature selector and k-nearest neighbors (KNN), Naïve Bayes (NB), Random forests (RF), and eXtreme Gradient Boosting (XGB) algorithms were used as classifiers. The evaluation was performed using the area under the receiver operator characteristic (ROC) curve (AUC), sensitivity, specificity and accuracy. Results: In univariate analysis, the highest AUC in pre-, post-, and delta-radiomic features were 0.78, 0.70, and 0.71, for GLCM_IMC1, shape (surface area and volume) and GLSZM_GLNU features, respectively. In multivariate analysis, RF and KNN achieved the highest AUC (0.85 AE 0.04 and 0.81 AE 0.14, respectively) among pre-and post-treatment features. The highest AUC was achieved for the delta-radiomic-based RF model (0.96 AE 0.01) followed by NB (0.96 AE 0.04). Overall. Delta-radiomics model, outperformed both pre-and post-treatment features (P-value <0.05). Conclusion: Multivariate analysis of delta-radiomic T2W MRI features using machine learning algorithms could potentially be used for response prediction in LARC patients undergoing nCRT. We also observed that multivariate analysis of delta-radiomic features using RF classifiers can be used as powerful biomarkers for response prediction in LARC.