This prospective study aimed to assess the predictive value of mono-exponential and multiple mathematical diffusion-weighted imaging (DWI) models in determining the response to neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC). The study included 103 LARC patients scheduled for preoperative chemoradiotherapy between December 2021 and June 2023 Magnetic resonance imaging (MRI) scans were performed using a 3.0-T MR scanner, encompassing sagittal, axial, and oblique coronal T2-weighted images without fat saturation, along with DWI perpendicular to the rectum's long axis. Various DWI parameters, including apparent diffusion coefficient (ADC), stretched exponential model (SEM), continuous-time random-walk model (CTRW), and fractional-order calculus model (FROC), were measured. The pathologic complete response (pCR) rate and tumor downstaging (T-downstage) rate were determined. After nCRT, SEM-α, SEM-DDC, CTRW-α, CTRW-β, CTRW-D, FROC-β, and ADC values were significantly higher in the pCR group compared to the non-pCR group (all P < 0.05). SEM-DDC, CTRW-α, CTRW-D, FROC-β, FROC-µ, and ADC values were significantly higher in the T-downstage group (ypT0-1) than in the non-T-downstage group (ypT2-4) (P < 0.05). The combination of CTRW (α + β + D) exhibited the best diagnostic performance for assessing pCR after nCRT (AUC = 0.840, P < 0.001). Pre-nCRT CTRW (α + β) demonstrated a predictive AUC of 0.652 (95%CI: 0.552-0.743), 90.3% sensitivity, and 43.1% specificity for pCR. Regarding T-downstage assessment after nCRT, the combination of CTRW (α + D) yielded the best diagnostic performance (AUC = 0.877, P = 0.048). In LARC patients, imaging markers derived from CTRW show promise in predicting tumor response before nCRT and assessing pCR after nCRT.
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