BB&T Contributing Editor
WASHINGTON — Ablation — the use of some type of energy to destroy a tissue —has been a therapeutic alternative for a fairly long time. And in the past several years the armamentarium of tools for using this strategy has grown, and, as it has grown, so have the number of procedures.
Many of these new ablative strategies were exhibited and discussed this year at the Annual Scientific Meeting of the Society of Interventional Radiology (SIR; Fairfax, Virginia).
BB&T in last month's issue discussed the use of focused ultrasound in the treatment of uterine fibroids ("Newest imaging: driving markets, competition heating up, pp. 5-9, April 2008). But this technology also is being used to treat breast cancer, prostate cancer and bone metastases. And the use of focused ultrasound is expanding rapidly, particularly outside the U.S.
The Sonablate 500 from Focus Surgery (Indianapolis) employs real-time 3D ultrasound imaging for guidance; and the Ablatherm HIFU (High Intensity Focused Ultrasound) system from EDAP (Vaulx-en-Velin, France) employs a trans-rectal probe for delivery of ultrasound energy in prostate cancer ablation.
As shown in Table 2 below, cumulative ablation procedures performed with the EDAP Ablatherm system have more than doubled since 2004. More than 4,000 ablation procedures have been performed using the Focus Surgery Sonablate system worldwide, and more than 3,500 women have been treated for uterine fibroids using the InSightec ExAblate system worldwide.
MR-guidance, as used in the ExAblate 2000, has the advantage of allowing tissue temperature to be mapped during the ablation procedure via MR thermography, and is also not affected by microbubbles that can cloud ultrasound images and reduce visibility of the targeted tissue during the ablation procedure.
An important advantage of HIFU is the ability of the technology to precisely target therapy to a specific location within the body, such as a focal tumor within the prostate, ablating only the tumor and sparing intervening nerves. For example, HIFU has the highest rate for maintenance of potency in the treatment of prostate cancer of any interventional treatment method, including surgery, external beam radiation, brachytherapy, and cryotherapy. HIFU also is being studied for use in the treatment of brain tumors, allowing non-invasive (that is, closed-skull) ablation of small tumor foci, such as brain metastases that often occur in patients with primary lung cancer.
HIFU is one of many minimally invasive ablation technologies increasingly being employed for cancer treatment.
Four other choices
Other technologies described at the SIR conference included radiofrequency ablation (RFA), cryoablation, microwave ablation, and electroporation.
RFA is the most widely utilized ablation technology at present, with three suppliers in the market, including Boston Scientific (Natick, Massachusetts), Angiodynamics (Queensbury, New York) and the ValleyLab division of Covidien (Mansfield, Massachusetts).
New developments in RFA include introduction of larger electrodes (for ablation of larger tumors more than 3.5 cm in diameter), improved control of ground pad currents to help avoid skin burns, and combination of RFA with TACE for improved minimally invasive eradication of tumors.
In addition, a new bipolar RFA electrode has been introduced in the U.S. by RFA Medical (Fremont, California), the InCircle bipolar RFA instrument. Bipolar RFA eliminates the need for a grounding pad, avoiding the risk of burns, and also provides faster ablation times than monopolar RF or cryoablation. With the system from RFA Medical, it is also possible to tailor the shape of the ablation zone to match the shape of the tumor, whereas conventional bipolar electrodes are limited to a spherical zone.
RFA is used mainly for treatment of liver tumors, but is also increasingly being employed in kidney cancer treatment (although presently accounting for less than 5% of kidney cancer procedures including surgical resection) and treatment of bone cancer.
New results presented at the SIR conference by Thierry de Baere, MD, of Institut Gustave Roussy (Villejuit, France) indicate that further expansion of RFA's applications to include lung cancer treatment may be in store for the future.
There is a significant need for more effective treatments for lung cancer, since surgical resection, curative in 80% of patients with other cancer types, is applicable to only 20% of lung cancer patients. The first use of RFA for lung cancer treatment was reported in 2000.
At the SIR conference, de Baere reported results from a series of 244 patients with non-small cell lung cancer who were not eligible for surgery and were treated with RFA. At two years, a survival rate of 70% was achieved, similar to the rate achievable via surgery in eligible patients, but with reduced side effects and shorter recovery time.
The main limitation for RFA in lung cancer therapy is the size of the lesion which can be treated of 4 cm. RFA may also replace surgical treatment for some patients, according to de Baere, for patients with smaller tumors.
Cyoablation for kidney cancer
New developments in cryoablation discussed at the conference include promising results using the technology for treatment of kidney cancer. About 54,000 new cases of kidney cancer and cancer of the renal pelvis are diagnosed in the U.S. annually, according to data from the American Cancer Society (Atlanta).
At the SIR meeting, Christos Georgiades, MD, PhD, of Johns Hopkins Hospital discussed results of recent studies of the use of cryoablation to treat kidney tumors. Cryoablation is less painful for the patient than other techniques such as RFA and surgery, and can be performed percutaneously without the need for general anesthesia. The technique can be used for larger tumors, with some lesions of up to 10 cm in diameter treated in the study described by Georgiades.
The success rate for controlling cancer in the study was from 90% to 100%, and was near 95% for tumors 4 cm in diameter or smaller. These results are essentially equivalent to surgery in terms of efficacy for smaller tumors, but hospital stay is reduced and cost is about one-third of that for surgical treatment. In addition, cryoablation can be used for patients who are not surgical candidates.
Suppliers of cryoablation systems include Endocare (Irvine, California) and Galil Medical (Yokneam, Israel). Expansion of the range of applications for cryoablation to include kidney cancer could generate new growth in the market, which has stagnated recently as demand for cryoablation therapy of prostate cancer, the current primary indication for the technology, has stabilized. Much of the new development focus in minimally invasive ablation, however, is in the emerging areas of microwave ablation and electroporation.
Companies developing microwave ablation technology for applications in minimally invasive cancer therapy include Covidien and NeuWave Medical (Madison, Wisconsin). Covidien plans to launch its VivaWave microwave ablation system in Q308. The system is based on technology acquired in the 2005 purchase of Vivant Medical, and has been FDA-cleared for soft tissue ablation since 2002.
Advantages of microwave ablation include lack of the need for a grounding pad, as is needed for monopolar RFA; a larger ablation zone ranging up to about 5 cm, readily expandable with the use of multiple probes; short ablation times; and lack of nerve stimulation as can occur with RF methods. Applications also are under development in the treatment of liver, kidney and lung cancer.
As discussed by Damian Dupuy, MD, of Brown Medical School (Providence, Rhode Island), microwave ablation using the Covidien system in patients with liver cancer has been performed on large tumors (up to 6 cm in size) in a two-stage, 20-minute procedure that would have required hours to complete using RFA. Dupuy said he believes microwave ablation will be particularly useful in lung cancer treatment, since penetration of microwave energy is expected to be high.
In the case of the Covidien system, a cooling sheath is used to cover most of the interventional probe except the tip, minimizing conductive heating of non-targeted tissue.
NeuWave, a new player in the microwave ablation sector, received $4.5 million in venture funding from firms including Venture Investors (Madison, Wisconsin) and Advantage Capital Partners (St. Louis, Missouri) in February 2008 to fund continued development of its microwave ablation system.
Indirect ablation with electroporation
One of the newest technologies to enter the ablation sector is electroporation, with a promising new technology under development by Angiodynamics. Electroporation does not directly ablate cells, but instead, when applied as a series of short (100 microsecond) high-voltage (1,000 to 1,500 volt) pulses, causes poration of cell membranes. Cells in the treated tissue then die via apoptosis, the natural cell death process, over the ensuing 24 hours.
The treatment is applied using small-diameter needles ranging from 16 to 19 gauge, and employs bipolar techniques. A 3 cm tumor can be treated in 40 seconds, less than one-10th the time required to treat a similar lesion using RFA. No heat is generated since current is low, and the treated zone is highly visible on ultrasound or CT images, showing a sharp differentiation between treated and untreated tissue. Another advantage is that electroporation does not appear to affect blood vessels or other collagenous tissue, including nerve fibers, allowing safe treatment of tumors that lie close to arteries and critical veins, as well as spinal tumors.
Angiodynamics has received FDA clearance for use of the electroporation system for soft tissue ablation, and is now applying for CE marking, with a target of launching the system in the market within the next two quarters.
Treating DVT and stroke
Another important application area for interventional radiology is treatment of peripheral vascular occlusions, including deep vein thrombosis (DVT).
More than 900,000 patients are treated annually in the U.S. for DVT, according to Gerard O'Sullivan, MD, of University College Hospital (Galway, Ireland), and up to two million have a condition that may benefit from treatment. However, the currently accepted treatment, anti-coagulant drug therapy, is only effective in helping to prevent the formation of new clots and does not eliminate existing thrombi that impede blood flow.
O'Sullivan reported on a large study involving 771 patients (827 limbs), most with acute thrombosis treated over a three-year interval beginning in February 2005 for DVT using the Trellis-8 Isolated Thrombolysis Catheter from Bacchus Vascular (Santa Clara, California). The Trellis device employs a dual balloon catheter system to isolate a clot in a blood vessel along with an oscillating wire to provide mechanical dispersion/maceration.
In addition, thrombolytic drugs are infused into the region between the balloons to lyse blood clots with the aid of mechanical dispersion. Lysed thrombus and residual drug can then be aspirated via the catheter, avoiding downstream migration of clot debris.
Furthermore, lower amounts of drug can be infused since the drug remains concentrated at the site of the clot, and this serves to avoid adverse effects such as bleeding complications that are prone to occur with systemic delivery of lytic drugs. There is also a lower likelihood of post-thrombotic syndrome (PTS) with the Trellis device, primarily due to removal of clots rather than lysis and downstream migration of clot debris.
Another advantage of the Trellis is the short procedure time that results from combining mechanical disruption with thrombolytic drugs. The average procedure time in the study was 22 minutes.
The existing Trellis device has an 8 Fr profile, enabling treatment of venous thrombosis. Bacchus Vascular plans to introduce a 6 Fr device in Q408 that will enable arterial thrombosis to be treated.
Another new device for the treatment of vascular thrombosis was introduced at the conference by Genesis Medical Interventional (Redwood City, California).
The F.A.S.T. Funnel Catheter system is FDA-cleared for performing proximal occlusion embolectomy/thrombectomy. The device uses an expandable funnel-shaped occluder at the tip of a small-diameter catheter to stop blood flow in the vessel containing a clot. The occluder is deployed just proximal to the thrombus, and expands automatically as a result of pressure from blood flowing through the proximal part of the occluder to the distal, impermeable portion, creating a seal against the vessel wall.
Flow in the region of the clot is stopped, preventing downstream migration of clot debris. Suction is then applied via a conventional syringe through a lumen in the center of the catheter, macerating the clot through the mechanical action of the mesh covering the occluder's surface and Focused Aspiration, in which all the suction is applied directly to the clot, and the resulting debris is removed.
The F.A.S.T. catheter, priced at $1,200, is intended for the non-surgical removal of emboli and thrombi, and for injection and aspiration of fluids.