Follow up after percutaneous MR-guided cryoablation of Small Renal Masses.

About 2-3% of newly diagnosed cancer concerns renal cell carcinoma (RCC).
Approximately 90% of all renal malignancies is accounted for by RCC, of which
approximately 80% consists of clear cell RCC. Over the last years the number of
incidentally diagnosed RCCs has been growing due to more frequent use of
abdominal imaging. Due to this the number of smaller and lower staged RCCs has
been growing over the last years.

Cryoablation
Currently most small renal tumors (masses <=7 cm) are treated by nephron sparing
surgery. However, partial nephrectomy better preserves renal function compared
to radical nephrectomy, possible disadvantage of this surgical approach remains
unintended damage of healthy kidney parenchyma due to a intraprocedural warm
ischemic time interval of the entire kidney. Also, surgery comes with
significant morbidity and might be unsuitable in case of previously performed
surgery, multiple tumors in an ipsilateral kidney or unsuitability for general
anesthesia due to the extent of co morbidities. Therefore, widespread interest
in more minimal invasive therapies, especially thermal ablative therapies, has
arisen the last couple of years. Studies regarding the effect of cryoablation
on tumor tissue have been studied before and showed the desired results.
Clinical studies proved cryoablation to be a safe treatment modality with low
risk of complications and promising results. Also the preservation of kidney
function seemed effective using cryoablation.

Intraprocedural imaging
In order to minimize the invasive character and thereby reducing post
interventional morbidity, cryoablation is currently mostly performed
percutaneously. Most challenging in case of percutaneous approach is to avoid
residual vital tumour tissue by adequately ablating the entire volume of the
tumour. Therefore, intraprocedural imaging is of utmost importance. The
advantage of CT imaging is good real time visualisation during the procedure,
however the patient will be explored to ionising radiation. MR imaging has all
the advantages of CT imaging, but enables monitoring without the need for
ionising radiation. Also differentiation between ice ball formation and other
surrounding anatomical structures are better visualised using MR imaging. Due
to its advantages MR imaging is the preferred imaging modality used in our
clinic. The reported technical success and complication rates using
percutaneous approach are excellent, regardless of imaging modality used.

Follow up imaging
Consensus on follow up imaging after percutaneous cryoablation is lacking.
Current guidelines state that the objective of follow up imaging should be
proper therapy effect evaluation and early and asymptomatic detection of
recurrent disease (local recurrence or distant metastasis). However, no
consensus is reached on the preferred imaging algorithm, mostly due to a lack
of prospective clinical studies validating imaging schedules or other high
quality evidence. Therefore current guidelines on follow up imaging are mostly
based on prognostic nomograms. The lack of consensus results in different
available guidelines that are equivocal and leave many decisions to the
discretion of the treating urologist. EAU guidelines propose first
post-procedural imaging at 6 months follow up, however, it is stated that a
stricter schedule may be required after cryoablation. In contrast AUA
guidelines are stricter and propose follow up imaging at 3 and 6 months
following cryoablation. In our clinic first post procedural imaging is
performed at 3 months follow up. In contrast, many radiologists recommend
earlier first imaging after ablation in order to detect residual tumour in an
early stage. Criteria for suspicion of residual disease on follow up imaging
are established and widely used, however interpretation of early performed
imaging may still be challenging due to post procedural peripheral rim
enhancement and increase in volume of the ablated region both not necessarily
indicating residual disease. Therefore biopsy should be performed to confirm
these early imaging findings.

Girentuximab
Previously the potential role of Fluorine-18-Deoxyglucose Positron Emission
Tomography (FDG-PET) in evaluating therapy efficacy after thermal ablation of
hepatic metastases has been studied. Interestingly FDG-PET revealed recurrences
earlier than conventional imaging techniques used. However FDG-PET has not
proven to have an additional value in diagnosis of RCC. More promising result
are seen in RCC using Single Photon Emission Computed Tomography (SPECT).
Carbonic Anhydrase IX (CAIX) is a cell surface antigen in renal cancer that is
highly and homogenously expressed in >95% of clear cell renal cell carcinoma
(ccRCC). Girentuximab (chimeric monoclonal antibody a.k.a. G250 or cG250) has a
high affinity for the CAIX antigen. Due to the specific targeting of
Girentuximab for ccRCC and the excellent options to visualize target lesions ,
especially when labelled with Indium-111, Girentuximab is already in use as a
diagnostic tool in case of renal masses for differentiation between benign and
malignant tumours. Also it has been proven efficient in determining new
metastatic sites. Because of the expression pattern, a positive lesion on
Indium-111-Girentuximab SPECT is always considered a malignant neoplasm of the
kidney, most likely ccRCC or a distant metastasis of that.

The primary objective is to evaluate the feasibility of early therapeutic
effect evaluation by performing early follow up imaging after percutaneous
MR-guided cryoablation of pT1a renal cell carcinoma. Secondary objective is to
assess the outcomes of the performed percutaneous MR-guided cryoablation
procedures of pT1a renal cell carcinoma at 3 months follow up.

After inclusion patients will undergo a pre procedural Indium-111-Girentuximab
SPECT scan (additional) after which a MR guided cryoablation is performed
(normal clinical practice). In case of proven targetting on the pre procedural
Indium-111-Girentuximab SPECT scan a second Indium-111- Girentuximab SPECT will
be performed 4-6 weeks after the treatment (additional). At the same time the
latter Indium-111-Girentuximab SPECT is performed a postprocedural MRI will be
performed (additional). Next imaging will be performed at 3 months post
procedural using MRI (normal clinical practice) after which a biopsy will be
taken from the ablative lesion to confrim imaging findings(additional).

Since the additional MRI and Indium-111-Girentuximab-DOTA SPECT are
experimental, the decision for eventual additional treatment due to residual or
recurrent disease will be made based on the follow up MR imaging and performed
biopsy at 3 months. In this matter, no individual benefit is established for
these patients. Individuals may benefit from the pre procedural
Indium-111-Girentuximab-DOTA SPECT as an additional diagnostic tool as for
histological exam of the taken biopsy sometimes is not representive. A positive
lesion is always considered a malignancy of the kidney, most likely a ccRCC.
Also the additional biopsy may reveal residual tumor after a false negative MRI
scan at 3 months follow up. In that case additional treatment will be
considered.
Potential risks are complications of MRI (burden of heating and noise, risks of
contrast reactions against gadolinium) and patient burden in form of time
investment and physical discomfort during biopsy and inserting an infusion
needle before imaging. No allergic reactions to Girentuximab have been observed
during clinical trials. The Indium-111-Girentuximab-DOTA SPECT comes with
minimal exposure to additional radiation (intravenous injection of 100 MBq
Indium-111-Girentuximab-DOTA and a low dose CT scan during SPECT CT scanning
results in an approximate effective dose of 8.3 mSv). Biopsy is associated with
low morbidity and with the current techniques used the risk of seeding is
negligible. The risk of the additional biopsy consists of spontaneously
resolving subcapsular/perinephric hematoma and hematuria. More severe bleeding
is rare (0-1.4%) and generally self limiting.

The only applicable group for undergoing experimental imaging after
cryoablation is the group that actually underwent renal tumor cryoablation,
therefore we select these patients for this study.