Purpose: To evaluate diffusion-weighted magnetic resonance imaging (DWI) for response prediction before and response assessment during and early after preoperative radiochemotherapy (RCT) for locally advanced rectal cancer (LARC). Methods and Materials: Twenty patients receiving RCT for LARC underwent MRI including DWI before RCT, after 10-15 fractions and 1 to 2 weeks before surgery. Tumor volume and apparent diffusion coefficient (ADC; b-values: 0-1000 s/mm(2)) were determined at all time points. Pretreatment tumor ADC and volume, tumor ADC change (Delta ADC), and volume change (Delta V) between pretreatment and follow-up examinations were compared with histopathologic findings after total mesorectal excision (pathologic complete response [pCR] vs. no pCR, ypT0-2 vs. ypT3-4, T-downstaging or not). The discriminatory capability of pretreatment tumor ADC and volume, Delta ADC, and Delta V for the detection of pCR was compared with receiver operating characteristics analysis. Results: Pretreatment ADC was significantly lower in patients with pCR compared with patients without (in mm(2)/s: 0.94 +/- 0.12 x 10(-3) vs. 1.19 +/- 0.22 x 10(-3),p = 0.003), yielding a sensitivity of 100% and specificity of 86% for detection of pCR. The volume reduction during and after RCT was significantly higher in patients with pCR compared with patients without (in %: Delta V-during: -62 +/- 16 vs. -33 +/- 16, respectively, p = 0.015; and Delta V-post: -86 +/- 12 vs. -60 +/- 21, p = 0.012), yielding a sensitivity of 83% and specificity of 71% for the Delta V-during and, respectively, 83% and 86% for the Delta V-post. The Delta ADC during (Delta ADC(during)) and after RCT (Delta ADC(post)) showed a significantly higher value in patients with pCR compared with patients without (in %: Delta ADC(during): 72 +/- 14 vs. 16 +/- 12, p = 0.0006; and Delta ADC(post): 88 +/- 35 vs. 26 +/- 19,p = 0.0011), yielding a sensitivity and specificity of 100% for the Delta ADC(during) and, respectively, 100% and 93% for the Delta ADC(post). Conclusions: These initial findings indicate that DWI, using pretreatment ADC, Delta ADC(during), and Delta ADC(post) may be useful for prediction and early assessment of pathologic response to preoperative RCT of LARC, with higher accuracy than volumetric measurements. (C) 2012 Elsevier Inc.