Trial Information

Medical and Economical Impact of Predicting the Response to Anti-Angiogenic Treatment in Metastatic Renal Cell Carcinoma Using Functional CT and MRI

The aim is to evaluate the capacity of functional CT and functional MRI to measure reliable
biomarkers capable of evaluating the efficacy of anti-angiogenic treatment.

Patient and methods

- Patients 200 patients with metastatic RCC will be enrolled in the study. Patients will be
recruited by an oncologist and the images will be acquired by a radiologist.

Patients will be followed until tumor progression (as defined by RECIST) or during 2 years
following inclusion if there is no progression.

- Imaging data acquisition Morphological and functional imaging will be obtained before the
beginning of the anti-angiogenic treatment, at 7±2 days and every 6 weeks until tumor
progression.

Progression is defined following the RECIST criteria.

- CT examination will be have two parts: the first one will be a dynamic acquisition
during 3 min (using low kV)focused on a "functional target lesion" during bolus
injection of a contrast agent for functional analysis, and the second one will be a
morphologic acquisition over the chest, the abdomen and the pelvis for RECIST
evaluation.

- MRI examination will have two parts: the first one will be a diffusion weighted
sequence focused on the same functional target as the one imaged on CT, and the second
one will be a dynamic acquisition using a T1 weighted gradient echo sequence with less
than 4 s sampling time during 5min following the bolus injection of contrast agent.

- Imaging data analysis The examinations will be anonymized and transferred to a
workstation for processing. Images will be processed by two independent readers.

Diffusion coefficient maps will be obtained using linear regression. The microvascular
parametric maps yielding as tissue blood flow, tissue blood volume, mean transit time,
permeability surface area product and tissue interstitial volume will be calculated for both
the CT and MRI dynamic series using a proprietary software by means of compartmental
modeling with an arterial input function (AIF).

Mean parameters will be recorded for different regions of interest (ROI) in the tumors
(whole tumor, periphery, center).

Morphological CT images will be analyzed following the RECIST criteria.

-Statistical analysis The functional parameters will be analyzed for inter-observer
reproducibility. The correlation between parameters obtained using functional CT and
functional MRI will tested.

Patients will be classified as good responders and poor responders according to RECIST
follow-up.

The correlation between each baseline functional parameter and the RECIST response will be
tested to evaluate the usefulness of the baseline parameters as predictors of response.

The correlation between each parameter's changes under treatment as compared to the baseline
value will be tested to evaluate the efficacy of each parameter to detect the response to
the anti-angiogenic drug. The precocity of the detection of the response using the parameter
variations will be also tested.

Finally, the economical impact of the use of the microvascular parameters as biomarkers of
treatment efficacy will be tested.