Liver and Kidney Tumours Clinical Trial
Official title:
Thermal Ablation With a Loosely Wound Helical Coil for Radiofrequency Treatment of Large Renal and Hepatic Tumors in Patients Undergoing Partial or Total Nephrectomy or Heptectomy
This is a clinical research study designed to determine the safety and efficacy of the
application of a unique interstitial radio frequency thermal therapy for the treatment of
large tumours in the kidney or liver. The novel device offers patients a more effective
therapy than conventional RFA and for patients with large tumours fewer number of treatments
and needle insertion sites. The clinical treatment volumes (or sites of focal tumours) will
be determined by a combination of biopsy and contrast enhanced CT imaging.
The study will assess if novel device can produce lesions in the liver or kidney in a
controlled and predictable manner and with sufficient size to effectively manage disease
progression in the organ. The extent of lesion size at a delivered power setting and
treatment time will be measured with post-treatment CT or MRI and biopsy as measures of
tissue response
Our group has developed a novel, interstitial induction coil device that has been designed to
coagulate large tumours (≥3cm) through a single needle insertion using heat in the range
55-90 ◦C. [31]Our system consists of a helical coil that is loosely wound inside the tumour
tissue or phantom and excited with radiofrequency energy at 27.12 MHz. The coil is
constructed from Nitinol, a shape memory alloy, to permit percutaneous deployment of the
device from a cannulating delivery needle into the tumor target. This novel monopolar device
has the potential to treat larger tumours with larger ablation zones (6cm x 4cm) with shorter
treatment time, in both ex vivo and in vivo settings. In our previous pig studies our group
has not seen a decrease in ablation volume compared to the ex vivo studies. The intent of
this research proposal is to determine the safety and efficacy of the application of a unique
interstitial coil electrode RF thermal therapy device for ablating large human renal and
hepatic tumors under US or CT guidance.
2. Hypothesis
Interstitial thermal therapy in the form of RF energy delivered percutaneously under US or CT
guidance with our newly developed novel coil electrode is a safe and effective method to
ablate large renal and hepatic tumors. This is an alternative to immediate surgery or to
surveillance with possible delayed treatment.
3. Objectives
3.1 To use the novel RF device and technique in liver tumor as developed in the porcine model
to patients with heptacellular carcinoma by:
3.1.1 Establishing that RF electrodes can be accurately and safely placed in the desired
location.
3.1.2 Establish the safety of energy application with the RF coil device including assessing
effect on surrounding liver tissue.
3.1.3 Verifying that large (>2cm) liver tumors are effectively ablated with RF energy.
3.2 To apply the novel RF device and technique in kidney tumor ablation as developed in the
porcine model to patients with renal cell carcinoma by:
3.2.1 Establishing that RF electrodes can be accurately and safely placed in the desired
location.
3.1.4 Establish the safety of energy application with the RF coil device including assessing
effect on surrounding kidney tissue.
3.2.2 Verifying that large (RFA Loosely wound thermal coil2cm) kidney tumors are effectively
ablated with RF energy.
4. Sample Size and Methods
4.1 RF ablation of renal tumor by:
4.1.1 Sample
Six patients with a large (large T1a and T1b N0 M0 RCC ,> 2 cm in diameter), solid renal mass
who are undergoing partial or radical nephrectomy deemed suitable for additional RFA will be
eligible.
The patients will be evenly split between two groups, namely the 'acute' and 'delayed'. With
the acute group, the study can meet its study objectives while minimizing the number of
procedures and evaluate the safety of the device with the patient in an OR suite. However, it
is difficult to predict tumor viability accurately based on cellular effects of the RF
treatment when the lesion is excised immediately after. The purpose of a delayed group
examines the full extent of histological thermal changes which do not occur until 6-7 days
after the treatment. This group will also validate the feasibility of the device within the
intended clinical setting of an interventional CT suite.
Patients who might be considered eligible for standard RFA or with irreversible coagulation
defects, urinary tract infection and/or morbid obesity will be excluded.
Only patients eligible for surgery for tumour resection will be enrolled. Patients will not
be randomised. The first 3 patients will go into the acute group (immediate arm). The reason
for this is to have a controlled setting should an incidence arise. The patient will already
be prepared for surgery, which will provide a more controlled environment, should there be a
patient safety issue.
4.1.2 Methods (Delayed Group)
The patient is admitted in the morning to the Medical Surgical Day Unit at the Toronto
General Hospital. Initial nursing assessment includes the documentation of vital signs and
allergies, and obtaining intravenous access. The patient is transported to the Department of
Medical Imaging, where care is provided by the Interventional Radiology team consisting of a
Radiologist, Radiology Nurse, and Radiology Technologist. Informed consent and satisfactory
blood work results (platelet count, INR, and PTT) are confirmed. Pre-treatment CBC and
creatinine will be measured and a urinalysis will be performed. Intravenous sedation is given
(midazolam, fentanyl, meperidine, and/or dimenhydrinate) during the continuous monitoring of
the patient, which includes pulse oximetry and blood pressure readings.
The appropriate area is aseptically prepared and draped, and the procedure is performed under
real-time US and CT guidance. Local anesthesia (e.g. 10 ml of 1% lidocaine) is administered
via a 25 gauge needle.
To ensure surrounding structures are protected from thermal injury, a "hydro-dissection
technique" may be applied which acts as a "thermal blanket" around the kidney proven to be
safe, effective, reproducible and inexpensive.
Using an electrically insulated 12ga introducer with trocar is inserted percutaneously into
the renal tumor. The needle tip will be placed 20mm from the center of the target. The trocar
is removed and co-axially (i.e. within the introducer), a core biopsy of the lesion is
performed with a 14-18 gauge needle. The radiofrequency applicator with a 14ga cannula
containing the loosely wound coil electrode is then optimally positioned and locked into the
introducer. Applicator is rotated to line up target with coil trajectory. Coil 'introducer
pliers' are used to deliver the coil into the tissue. Four dispersive electrodes (grounding
pads) are adhered on the thighs of the patient. The applicator is connected to the generator
and grounding pads. Energy will be applied in a single heating cycle for 4-10 minutes at a
power rating set between 125-200W based on manual feedback and size of target. Development of
the thermal lesion will be monitored with real time B mode US. At the end of the procedure
the coil electrode is retracted with aid of the 'rectractor pliers' and then applicator with
introducer is removed.
US or CT imaging is used during and immediately after RF to ensure accuracy of the thermal
lesion created and to exclude complications. After completion of the procedure, the patient
is transported to the Medical Surgical Day Unit for observation, recovery, and further pain
control as required. Immediate post-treatment CBC and serum creatinine levels will be
measured. Urinalysis will be performed. The patient is discharged home accompanied by a
relative or a friend approximately 4 hours after completion of the RF procedure.
A follow-up contrast-enhanced spiral CT scan will be performed on approximately
post-treatment day 6-10 (prior to the surgery) to assess possible complications and to
measure the size of the lesion and degree of enhancement. In addition, CBC, serum creatinine
and urinalysis will be performed.
On approximately day 6-10, a partial or radical nephrectomy will be performed in the usual
way. In the cases of partial nephrectomy, it is assumed that clear margins will be grossly
visible around the tumors to aid in the resection through normal tissue.
The specimen will be sent to pathology where thermal lesion sizes will be measured by gross
inspection. Histo-pathology using standard H&E and NADH will establish the boundaries of the
thermal lesion and detect any viable cells within this region. It will also establish the
extent of coagulative necrosis in the normal surrounding kidney tissue. Further follow-up of
the patient will continue as per standard protocol for RCC.
4.1.3 Methods (Acute Group)
In either the image guided therapy operating room (MPOR) or in the routine operating room at
Toronto General Hospital the patient will be put under general anaesthesia.. A needle core
biopsy will be taken from the lesion and sent to pathology for routine examination to ensure
that an accurate diagnosis can be made if the subsequent thermal therapy alters the
appearance of the tissue. A "hydro-dissection technique" is then applied to ensure
surrounding structures are protected from thermal injury, which acts as a "thermal blanket"
around the kidney.
The RF electrode will be inserted directly or percutaneously into the lesion, depending on
the imaging modality (US or CT guidance) and deployed with same method as previously
described in the 'delayed group'. Energy will be delivered using the single timed heating
cycle. Treatment will be monitored with B mode US. Once the cycle is completed, the probe
will be removed and the planned surgery will continue with partial or radical nephrectomy.
The specimen will be sent to pathology and processed as above.
For patients that have an ultrasound guided procedure, the RFA procedure will be done in the
routine operating room in an open fashion, the kidney will be exposed surgically in the usual
way in anticipation of the partial or radical nephrectomy. The kidney tumour will be located
by gross inspection, palpation and with the aid of intraoperative US if required. In this
case, the RFA probe will be inserted directly into the lesion. For those patients that have a
CT guided procedure along with US, the procedure will be done in the MPOR and the RFA probe
will be inserted percutaneously into the lesion, prior to opening and exposing the kidney. If
the surgery is unable to be performed in the MPOR, the patient will transferred to a routine
operating room, while under general anesthetic, to have their surgery. They will be
accompanied by the anesthesiologist.
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