Impact of Predicting Anti-angiogenic Response in mRCC Using Functional Imaging
Condition: Carcinoma, Renal Cell
MeSH terms: Carcinoma; Carcinoma, Renal Cell
Study type: Observational

Summary: 
      The goal is to study the impact of functional MRI and CT evaluation of changes in tumor
      vessels induced by anti-angiogenic treatment in patients with metastatic RCC.

      The hypothesis is that good responders and poor responders will have different responses
      induced by anti-angiogenic treatment, and that the detection of theses changes by functional
      imaging can improve the therapeutic management.

      Functional CT and MRI will be performed in 200 patients before the beginning of
      antiangiogenic treatment, 7 days after and every 6 week until tumor progression (as defined
      by the RECIST criteria). Perfusion and diffusion parameters will be measured using a
      dedicated software.
    

Detailed description: 
      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.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        oncologic hospital visit
      
Keywords: Carcinoma, Renal Cell [C04.557.470.200.025.390]; Angiogenesis Inhibitors [D27.505.954.248.025]; Tomography Scanners, X-Ray Computed [E07.913]; Magnetic Resonance Imaging [E01.370.350.825.500]; Diffusion Magnetic Resonance Imaging [E01.370.350.825.500.150]; Perfusion [E05.680]