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

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% AACIDkurtosis and Δ% AREX25th 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