## 3 Imaging Evaluation of Therapy Response in Metastatic RCC
### Antiangiogenic Therapies
\\ \hline \multirow{4}{*}{**Partial Response (PR)**} & \multirow{4}{*}{Decreased (\(\geq\)30\%) sum of \(\geq\)30\%) sum of \(\geq\)30\%)} & \multirow{4}{*}{Decreased (\(\geq\)10\%) sum of the target lesions longest} \\  & & Decreased (\(\geq\)10\%) sum of \(\geq\)30\%) sum of  
size of metastatic lesions is due to intratumoral edema or necrosis induced by therapy and not to disease progression, as expected; other times, lesions increase in size and attenuation due to intratumoral hemorrhage induced by starvation of blood supply. In particular, the appearance of a fluid-fluid level within the lesion is expression of intratumoral hemorrhage, MRI may be helpful to identify blood in such cases [10]. The appearance of new lesions is the most misleading atypical response pattern; sometimes metastatic lesions may not be identified at baseline because they have the same density of the surrounding parenchyma, but after treatment they may be detectable as a result of decreased (edema or necrosis) or increased (hemorrhage) CT attenuation [10]. Moreover, the sharp and smooth margins of the lesions represent a useful sign of good response during follow-up [10]. To date, even though the atypical response patterns incidence is not well known, radiologists should take them into account when evaluating patients in treatment with antiangiogenic drugs. The evaluation of all lesions' behaviors and the correlation with clinical data are often useful; in case of doubt, a CT revaluation after a few weeks (6-8) can be suggested [10]. Since antiangiogenic therapy affects tumor perfusion, the non-invasive assessment of tumor vascularity represents a challenging endpoint for radiologists that could provide information of treatment response. Perfusion parameters can be assessed by using contrast-enhanced ultrasound and dynamic contrast-enhanced CT, as well as non-enhanced MRI (arterial spin-labeling MR imaging) and dynamic contrast-enhanced MRI sequences. The dynamic contrast-enhanced imaging techniques are based on the temporal changes in tumor tissue echogenicity/attenuation/intensity after intravenous administration of contrast medium as a bolus. The parameters of microcirculation (tissue blood flow and volume, tissue interstitial volume and mean transit time) are extracted from the tumor tissue enhancement curves. Among the imaging techniques, the CT perfusion approach is preferred for different reasons. First, it is easy to implement because there is a direct correlation between attenuation (HU) and concentration of contrast agent, obtaining perfusion parameters by mathematical models [8]. Secondly, since multidetector CT equipment have a large anatomic coverage and RCC metastases usually appear in the lung bases and in the upper abdomen, all lesions can be assessed in the same acquisition, unlike MRI and ultrasound which usually allow to evaluate one anatomic district [5]. Perfusion changes as well as attenuation modifications normally precede changes in size, so perfusion CT could aid to assess therapy response and to identify non-responder patients at an earlier point. Furthermore, the means of blood flow measurements allow to identify focal areas of new tumor perfusion, expression of resistance and/or of progressive disease. Based on perfusion parameters, clinicians could modify dose and schedule of the therapy or switch to another drug [27]. Even though perfusion CT parameters turned out to be a non-invasive early indicator of efficacy of antiangiogenic therapy, they currently remain investigational and their role in clinical practice has not been yet defined [28]. Figure 1 illustrates an example of a patient with metastatic clear cell RCC treated with antiangiogenic drugs showing SD (Table 1).