CEST-MRI assessment of locally advanced pMMR rectal cancer for prediction of immune activation status following radiotherapy.

Abstract

To evaluate whether chemical exchange saturation transfer MRI (CEST-MRI) enables early prediction of treatment response to subsequent immunochemotherapy following radiotherapy in patients with proficient mismatch repair (pMMR) locally advanced rectal cancer (LARC). In this prospective single-center study, consecutive pMMR LARC patients, who underwent short-course radiotherapy followed by neoadjuvant immunochemotherapy and surgery, were enrolled between January 2024 and March 2025. Routine MRI and CEST-MRI were acquired at baseline and 1 week after radiotherapy. CEST-derived tumor metabolism and pH metrics were extracted, and absolute change (Δ) and percentage change (Δ%) were calculated. Patients with pathological complete response (pCR) were classified as good responders, while those with non-pCR were defined as poor responders. A multivariable model was constructed, and receiver-operating characteristic (ROC) curves were generated to evaluate diagnostic performance. Forty patients (mean age, 56.8 ± 8.8 years; 24 men) were enrolled, 22 (55%) achieved pCR and 18 (45%) were non-pCR. CEST metrics showed significant differences between good responders and poor responders after radiotherapy. Based on multivariate logistic regression analysis, Δ% AACID_kurtosis and Δ% AREX_{25th percentile} were included in the model. The accuracy, sensitivity, and specificity of the model were 0.850 (95% CI: 0.702, 0.943), 0.778 (95% CI: 0.524, 0.936), 0.909 (95% CI: 0.708, 0.989), with an AUC of 0.889 (95% CI: 0.749, 0.966; p < 0.001). Metrics representing tumor metabolism and pH assessment by multiparametric CEST-MRI enable early prediction of treatment response to subsequent immunochemotherapy following radiotherapy in pMMR LARC, thereby informing early treatment decision-making. Question Noninvasive methods to capture early post-radiotherapy immune microenvironmental changes and predict response to subsequent immunochemotherapy in pMMR LARC remain unavailable. Findings Chemical exchange saturation transfer MRI can characterize tumor metabolism and pH and predict response to subsequent immunochemotherapy 1 week after radiotherapy in LARC. Clinical relevance Chemical exchange saturation transfer MRI provides an imaging-based, noninvasive biomarker for early post-radiotherapy response stratification in patients with pMMR LARC 1 week after radiotherapy, thereby informing timely treatment decisions for subsequent immunochemotherapy.