Objectives 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). Materials and methods 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. Results 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 < 0.001). Conclusion 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. Key Points <Emphasis Type="BoldItalic">Question</Emphasis> Noninvasive methods to capture early post-radiotherapy immune microenvironmental changes and predict response to subsequent immunochemotherapy in pMMR LARC remain unavailable. <Emphasis Type="BoldItalic">Findings</Emphasis> Chemical exchange saturation transfer MRI can characterize tumor metabolism and pH and predict response to subsequent immunochemotherapy 1 week after radiotherapy in LARC. <Emphasis Type="BoldItalic">Clinical relevance</Emphasis> 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. Graphical Abstract

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

期刊论文
发表日期：

2026年4月4日

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Ziwei Jin,
Lan Zhang,
Chuansheng Zheng,
Fan Yang,
Na Hao,
Liza Mao,
Bin Chi,
Yuan Liu,
Peng Sun,
Ning Zheng,
Haihong Wang,
Zhenyu Lin,
Xin Li

摘要

Objectives

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).

Materials and methods

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.

Results

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).

Conclusion

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.

Key Points

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.

Graphical Abstract