Riaz et al. showed that combining measurements of the entire tumor and of its enhancing portion (especially WHO and EASL) could increase complete pathological response detection.[4] Considering imaging as a potential surrogate mTOR inhibitor marker of pathological response to liver-directed therapies, we advocate that combining anatomical and functional criteria are currently to be considered the next steps of research. Among these, DWI could play an important role as a potential adjunct tool in response assessment after Y90. However, when used as unique response criteria, ADC calculation was disappointing for detection of pathological response. However, our results necessitate some comments.

ADC calculation methodology was heterogeneous in the literature and highly debated. Also,

DWI sequences parameters are still to be defined (use of b-values, echo-planar versus spin-echo, and single versus multishot sequences). Some researchers propose calculating ADC values in the entire lesion (necrotic or viable), wheras others advocate studying only the borders. Even if automated segmentation software is available, some prefer a manual FK866 drawing of the ROI. Finally, a choice must be made between measurements directly performed on ADC maps or calculated after measurements on both low and high b-value sequences series, that is, bypassing automated postprocessing ADC calculation (we chose this latest methodology to optimize the accuracy of series coregistration). Whatever the chosen methodology, we have to accept advantages and disadvantages. As a potential optional tool in response assessment for borderline cases, we opted 3-mercaptopyruvate sulfurtransferase for a

more restrictive and discriminant technique; when possible, we placed our ROI on the suspected viable portions of the tumors. However, baseline and posttreatment ADC values in our study (baseline: median, 1.5; range, 1.0-2.2; 1 month: median, 1.5; range, 0.7-2.9; 3 months: median, 1.5; range, 1.1-2.7) were consistent with other studies evaluating ADC changes after TACE and sorafenib. Despite equivocal results in our study, we recognize that ADC could constitute a useful optional tool in clinical practice for borderline cases. For instance, one of the investigators (F.M.) showed better results in subjectively estimating CPN, partially because of DWI as ancillary data. Further improvements in ADC methodology and software (i.e., volumetric ADC mapping) would be beneficial. The use of ADC after sorafenib may be problematic because patients may develop hemorrhagic necrosis as a favorable treatment response, which can decrease ADC values and hence mimic residual tumor.[12, 13] There are strengths to this study. This is the first radiological/pathological correlative study generated from a prospective, randomized trial; these are rare. Second, the analysis was comprehensive and investigated relevant parameters, including size (WHO and RECIST), enhancement (EASL and mRECIST), and functional imaging criteria (DWI).