**5. Criterios RECIST/MASS/CHOI**

95% CI 46.1 to 74.6%). The percentage decrease in Ktrans and change in tumor size was sig‐

Finally, molecular techniques such as PET show a limited role in the study of metastatic re‐ nal cancer, since this tumor usually has a low activity of glucose metabolism (pathway as‐ sessed by 18F-fluorodeoxyglucose, the most widely used radiotracer). Only in cases where the tumor shows an increased metabolism of glucose, PET may be useful in the assessment of the disease and its response to therapy. Other radiotracers that allow the study of impor‐ tant characteristics such as tumor hypoxia, cell proliferation or angiogenesis itself, are still under evaluation and implementation in clinical practice [56]. In an experimentally way it is evaluating the introduction of functional imaging techniques in clinical studies, to develop translational research in oncology imaging applications. In a NCI trial, Dr. Hoffman (Uni‐ versity of Utah) is using DCE-MRI and various types of PET (H2150-PET, FDG-PET, FDL-

nificantly associated with progression-free survival (p = 0.01 and 0.05, respectively).

PET) in monitoring response to multi-targeted treatment in renal cancer patients.

We must consider several issues when assessing the therapeutic response of tumors. The morphological assessment with quantification of changes in size used in the RECIST criteria ("Criteria in Solid Tumors Response") has been our main concern when assessing tumor re‐ sponse [2]. This approach seems true for the use of cytotoxic drugs. However, this assess‐ ment is limited, since the macroscopic changes take time to become evident, often are not specific and do not provide information on the physiological and molecular component of

Advances in the field of oncology have led to the development of new drugs in renal cancer as sunitinib, sorafenib, pazopanib, tivoaznib, axitinib, temsirolimus, everolimus and bevaci‐ zumab [46]. These drugs (mainly cytostatic) cause little change in lesion size. Therefore, RE‐ CIST criteria are not entirely suitable for assessing tumor response, and proper techniques

The recent emergence of techniques for the functional study of angiogenesis, such as perfu‐ sion CT or dynamic MRI allow obtaining quantitative parameters (blood volume, blood flow mean transit time, ktrans Ve, etc.) and would open a interesting field for assessing tu‐ mor response in a more objective [57] [58] [59]. This could open the door to the development of a strategy based on the image for the selection of patients to be treated with antiangiogen‐ ic therapies. However, each of these techniques has advantages and disadvantages. Thus, CT perfusion shows the drawback of radiation necessary for conducting the studies, where‐

as in the case of dynamic MRI the analysis of the results is much more complex.

**4.1. Evaluation of response: Antiangiogenics and mTOR inhibitors**

will vary according to the mechanism of action of the drug.

**3.3. PET**

58 Renal Tumor

**4. Response evaluation**

tumors [42].

Classically, oncology response evaluation is based on comparison of pre and post-treatment tumor volume by studying changes in the diameter of the tumors. RECIST criteria in its original version and its 2009 Update 1.1 are applied routinely in oncology practice [2]. How‐ ever, it is recognized that the response evaluation focused exclusively on size changes have important limitations, including the importance of excluding changes in tumor metabolism or not considering the appearance of necrosis or fibrosis as a factor which may be related to response to treatment. Furthermore, the introduction of new drugs creates the need for a different evaluation of the tumor and treatment response [46].

The limitations of traditional approaches, as the criteria of the World Health Organiza‐ tion (WHO) or Response Evaluation Criteria in Solid Tumors (**RECIST**) in the evaluation of targeted therapies have been widely documented [64] [65] [57]. Therapies that act on tumor vascularity may have underestimated clinical benefit by tumor size change since their mechanism of action (more cytostatic that cytotoxic), produces more stabilization than tumoral responses.

Without abandoning the use of size criteria as a key element in the assessment of patients with metastatic renal cancer, some authors have attempted to obtain early information (**EP‐ TIC**, Early English Post-herapy Imaging Changes) [66] on the prognosis of patients treated with therapy acting at the VEGF pathway. In this regard, it was demonstrated that a 10% decrease in the sum of the largest diameters of the lesions in the first control, provides infor‐ mation on the subsequent course of patients. Using only tumor size as endpoint criterion would leave aside the use of IV contrast.

Subsequently it was observed a relationship between the degree of tumor enhancement be‐ fore therapy and the likelihood of response (being higher in those tumors with greater pre‐ treatment enhancement). Many of these new drugs induce tumor necrosis, causing a dramatic drop in the enhancement of metastatic lesions in the post-therapy evaluation [67]. Based on these observations and on previous experience with gastrointestinal stromal tu‐ mors treated with imatinib, a set of tumor response criteria based on changes in size and / or density tumor was established: Choi criteria, modified Choi criteria, MASS criteria and SACT criteria (Table 1) [56].


**Criterio Targeted**

**SCAT** Criteria

**MASS** criteria

**Functional and molecular image.**

Hounsfield Unit.

Unit.

(63)

(29)

**lesions**

Tumor size 10 mm

Maximum of 10 target lesions

**Complete response**

**Partial response**

Decrease in tumor size 20%

Decrease in tumor size10% and \_half of the non-lung target lesions with 20 HU decreased mean attenuation

Favorable response. No new lesions and any of the following: 1. Decrease in tumor size 20 % 2. One or more predominantly solid enhancing lesions with marked central necrosis or marked decreased attenuation ( 40 UH)

**Stable disease Progressive disease**

Imagen Thecniques in Renal-Cell Carcinoma http://dx.doi.org/10.5772/54190

> Increase in tumor size 20%

61

New metastases, marked central fill-inc of a target lesion or new enhancement in a homogeneously hypoattenuating nonenhancing mass

Any of the following: 1. Increase in tumor size of 20 % in the absence of marked central necrosis or marked decreased attenuation 2. New metastases, marked central fill-in, or new enhancement of a previously homogeneously hypoattenuating nonenhancing mass

Does not meet criteria for PR or PD

Does not meet criteria for favorable or unfavorable response

No response criteria defined

CR: complete response. PR: partial response. NC: no changes. PD: progressive disease. RECIST: Response Evaluation Criteria in Solid Tumors. CT: computed tomography. SACT: criteria size and attenuation CT (SACT) criteria. HU:

CR: complete response. PR: partial response. NC: no changes. PD: progressive disease. RECIST: Response Evaluation Cri‐ teria in Solid Tumors. CT: computed tomography. SACT: criteria size and attenuation CT (SACT) criteria. HU: Hounsfield

Each of these criteria has a number of advantages compared to RECIST, but some limita‐ tions. So **Choi criteria**, based on the change in size or tumor density on CT (% change in the measured attenuation value at UH), show little advantage over RECIST when establishing the possibility of a long-term response. Furthermore, these show a different utility criteria

**Table 1.** CT-based criteria for response evaluation of targeted therapies in renal cell carcinoma.


**Criterio Targeted**

**RECIST version 1.1 (2)**

60 Renal Tumor

**EPTIC (Early Posttherapy Imaging Changes)** (60)

**Choi Criteria (61) (3)**

**Modified Choi Criteria** (62)

**lesions**

Tumor size 10 mm by CT scan

Tumor size 15 mm by chest X-ray

Maximum of 5 target lesions

Tumor size 15 mm

Maximum of 10 target lesions

Tumor size 15 mm

Maximum of 10 target lesions

**Complete response**

Disappearance of all lesions

Disappearance of all lesions

No new lesions

Disappearance of all lesions

No new lesions

**Partial response**

Decrease in size 30%

No PD of nontarget lesions

A decrease in size 10% or a decrease in tumor attenuation (HU) 15% on CT

No new lesions , no obvious progression of nonmeasurable disease

A decrease in size 10% and a decrease in tumor attenuation (HU) 15% on CT

No new lesions , no obvious progression of nonmeasurable disease

**Stable disease Progressive disease**

Increase in tumor size 20% (the sum must also demonstrate an absolute increase of at least 5 mm)

Increase in tumor size 10% and does not meet criteria of PR by tumor attenuation

New lesions

Increase in tumor size 10% and does not meet criteria of PR by tumor attenuation

New lesions

Does not meet criteria for PR or PD

Does not meet criteria for CR, PR or PD

No symptomatic deterioration attributed to PD

Does not meet criteria for CR, PR or PD

No symptomatic deterioration attributed to PD

No new lesions No new lesions New lesions

Establishing the prognosis depending on the % size decrease after antiangiogenic therapy Decreased size ≥ 10%= good prognosis.

> CR: complete response. PR: partial response. NC: no changes. PD: progressive disease. RECIST: Response Evaluation Cri‐ teria in Solid Tumors. CT: computed tomography. SACT: criteria size and attenuation CT (SACT) criteria. HU: Hounsfield Unit.

**Table 1.** CT-based criteria for response evaluation of targeted therapies in renal cell carcinoma.

Each of these criteria has a number of advantages compared to RECIST, but some limita‐ tions. So **Choi criteria**, based on the change in size or tumor density on CT (% change in the measured attenuation value at UH), show little advantage over RECIST when establishing the possibility of a long-term response. Furthermore, these show a different utility criteria depending on the type of drug tested, being most useful in the case of sorafenib (which tends to cause more degree of necrosis in lesions) than for sunitinib.

**Author details**

, M. Ramos2

and L. A. Aparicio7

, M. Lázaro3

\*Address all correspondence to: Aparicio@sergas.es

2 Centro Oncológico de Galica, A Coruña, Spain

3 Complexo Hospitalario Universitario, Vigo, Spain

4 Hospital Universitario Lucus Augusti, Lugo, Spain

5 Complexo Hospitalario Universitario de Ourense, Ourense, Spain

6 Complexo Hospitalario Arquitecto Marcide, Ferrol, Spain

7 Complexo Hospitalario Universitario, A Coruña, Spain

1.1). Eur J Cancer 2009, Jan;45(2):228-47.

lation. Radiology 1996, Mar;198(3):785-8.

ology. World J Urol 2011, Oct;29(5):633-8.

col 2007, May 1;25(13):1753-9.

, S. Vázquez4

1 Complexo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain

[1] Cohen HT, McGovern FJ. Renal-cell carcinoma. N Engl J Med 2005, Dec 8;353(23):

[2] Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version

[3] Choi H, Charnsangavej C, Faria SC, Macapinlac HA, Burgess MA, Patel SR, et al. Correlation of computed tomography and positron emission tomography in patients with metastatic gastrointestinal stromal tumor treated at a single institution with im‐ atinib mesylate: Proposal of new computed tomography response criteria. J Clin On‐

[4] Jamis-Dow CA, Choyke PL, Jennings SB, Linehan WM, Thakore KN, Walther MM. Small (< or = 3-cm) renal masses: Detection with CT versus US and pathologic corre‐

[5] Siracusano S, Bertolotto M, Ciciliato S, Valentino M, Liguori G, Visalli F. The current role of contrast-enhanced ultrasound (CEUS) imaging in the evaluation of renal path‐

, M. C. Areses5

, O. Fernandez5

, U. Anido1

Imagen Thecniques in Renal-Cell Carcinoma http://dx.doi.org/10.5772/54190

,

63

L. León1

J. Afonso6

**References**

2477-90.

**Modified Choi criteria** evaluate existing changes in both size and tumor density after treat‐ ment. These criteria could differentiate those patients at risk of disease progression, but shows a tendency to classify patients as responders.

**SACT criteria** (Size and Attenuation CT) differ from the modified Choi criteria that estab‐ lish an absolute value of change in tumor density (> 20 UH) rather than a % of change. These criteria are more reliable in the case of low attenuation pre-therapy lesions, in which it is easier to obtain a percentage decrease in density.

Finally, the **MASS criteria** (Morphology, Attenuation, Size, and Structure) include morpho‐ logical and structural elements regardless of the size and density of lesions. These criteria are intended to take into account the extensive necrotic changes frequently associated with tumor response to these drugs [63].

However, both SACT as MASS criteria are complicated and basically useful in differentiat‐ ing patients with a long progression-free survival (> 250 days) of those showing a rapid pro‐ gression (<250 days). Overall, we consider that in all these criteria contrast enhancement of lesions plays a major role, so that both imaging protocols (volume of contrast acquisition phase, etc.) or factors such as cardiac function patient can significantly influence the results.
