## 3 Imaging Evaluation of Therapy Response in Metastatic RCC
### Antiangiogenic Therapies  
As previously described, antiangiogenic drugs achieve a cytostatic effect reducing tumor perfusion and consequently inducing lesion necrosis. In this setting, different studies highlighted that changes in tumor CT attenuation values anticipate changes in lesion size, predicting treatment response. In particular, [PERSON] et al. noticed that higher response rates correlates with higher CT enhancement values of metastases before treatment, as well as [PERSON] et al. found that the presence of necrosis, as CT hypodensity, was associated with more favorable therapeutic outcome [22; 23]. Conversely, the appearance of central areas of enhancement in previously hypodense lesions during treatment was indicative of disease progression [24]. For these reasons and for the cytostatic effect of antiangiogenic therapies, RECIST, based only on dimensional evaluation of tumor burden, are not accurate to assess such treatment response. New imaging criteria, firstly Choi and then modified Choi (mCHOI), have been proposed for this purpose (Table 1) [17; 25; 26]. In particular, [PERSON] et al. compared the assessment of tumor response in metastatic RCC patients treated with sunitinib according to RECIST, CHOI and mCHOI criteria. All of these three different criteria assess treatment response by measuring tumor burden as the sum of the target lesions diameters, but the most important difference among these three criteria is the evaluation of partial response (PR) for which RECIST consider only significant changes in tumor size (\(\geq\)30%), while CHOI and mCHOI account for slight changes in tumor size (\(\geq\)10%) alternatively present with tumor CT density decrease (\(\geq\)15%) (CHOI) or associated with tumor CT density decrease (\(\geq\)15%) (mCHOI). Thus, not only tumor size changes, but also tumor density changes are considered in these new treatment response criteria. In this regard, [PERSON] et al. reported in their systematic study that only mCHOI criteria were able to accurately stratify patients for both overall survival and progression-free survival (PFS) better correlating with the clinical outcome compared to CHOI and RECIST criteria [26]. Therefore, these new criteria (CHOI and mCHOI) account for tumor response morphstructural tumor changes represented by changes in lesion size and/or CT density; this novel approach seems to be more accurate than RECIST since CT density tumor changes may be earlier than changes in lesion size; thus, CHOI and mCHOI may be able to early identity responders patients to antiangiogenic therapies, even though significant decrease of tumor burden is not observed. However, some methodological CT aspects should be underlined since these may influence imaging results, potentially limiting the accuracy of these criteria; in this regard, scanning time, concentration of contrast medium and measurement of CT density have yet not been standardized for these purposes. The specific action mechanism of antiangiogenic agents explains the atypical response patterns and radiologists have to know them to avoid pitfalls. Sometimes the increase in  
\begin{table}
\begin{tabular}{c c c c} \hline \hline
**Response** & **RECIST 1.1 [17]** & **Choi Criteria [25]** & **Modified Choi Criteria [26]** \\ \hline \multirow{4}{*}{**Complete Response (CR)**} & No evidence of target and & No evidence of target and & No evidence of target and \\  & non-target lesions; & non-target lesions; & non-target lesions; \\  & Short axis of lymph & Short axis of lymph & Short axis of lymph \\  & node(s) \(<\) 10 mm; & node(s) \(<\) 10 mm; & node(s) \(<\) 10 mm; \\  & No new lesions. & No new lesions. & No new lesions.