BBI Contributing Editor

PHOENIX, Arizona The market for products used in interventional radiology is a diverse and growing segment of the medical device market, totaling approximately $500 million in 2002 in the U.S. and projected to grow to more than $800 million by 2005. The market includes products used in both vascular and visceral procedures and encompasses applications such as peripheral vascular stenting and angioplasty, endovascular graft implantation, dialysis access, cancer therapy and the treatment of venous disease. The 29th annual scientific meeting of the Society of Interventional Radiology (SIR; Fairfax, Virginia), held here in late March, addressed the latest developments in technology as well as new clinical applications in the field of interventional radiology.

Carotid stenting is one example of a new application that is poised to enter mainstream practice, creating a new segment of the market that by some estimates could reach $600 million in the first year. Peripheral vascular stents for treatment of occlusive disease in other vessels already represent a major segment of the market, and one that is continuing to expand as new applications are developed and patients increasingly opt for less invasive therapy as an alternative to surgical bypass. New technologies for maintaining hemodialysis access are under development that will help address the expanding number of patients with end-stage renal disease and drive further growth in the interventional radiology market. Varicose vein treatment is another growth area of the market that is beginning to attract strong interest from a broader spectrum of practitioners, and which has the potential to expand to a segment encompassing well over 1 million procedures annually worldwide. In the future, experts presenting at the conference expect cancer therapy to become one of the largest applications in the interventional radiology market, aided by advances in noninvasive imaging technologies that are now providing an unprecedented ability to precisely identify tumors at an early stage and guide targeted interventions to eradicate the disease.

In yet other new developments, computerized simulation technologies are now being introduced to the market that will enhance the ability of interventional radiologists to perform complex procedures and improve the efficiency of training new specialists.

Peripheral vascular therapy devices

A leadoff symposium at this year's SIR conference covered the latest developments in carotid stenting. Carotid stenting is under development as a treatment to prevent stroke in patients with carotid artery stenosis. About 2 million people suffer a stroke worldwide each year, and about 25% are caused by carotid atherosclerosis. At present, the standard treatment for carotid artery disease is carotid endarterectomy, a surgical procedure that was performed on 175,000 patients in the U.S. in 2003, according to Gary Roubin, MD, of Lenox Hill Hospital (New York). Carotid artery stenting offers a less-invasive treatment approach that is particularly attractive for the treatment of high-risk patients. Major advances were reported in two clinical trials of carotid stents the ARCHeR (Acculink for Revascularization of Carotids in High Risk Patients) trial, employing the Acculink stent and Accunet embolic protection filter from Guidant (Indianapolis, Indiana), and the SAPPHIRE (Stenting and Angioplasty with Protection in Patients at HIgh Risk for Endarterectomy) trial, using the Precise Stent and Angioguard Filter from Cordis Endovascular (Warren, New Jersey). As discussed by Mark Wholey, MD, of Pittsburgh Vascular Institute (Pittsburgh, Pennsylvania), high-risk patients such as diabetics showed a particularly impressive benefit in the SAPPHIRE trial, with a 2.4% incidence of heart attacks in the stent group vs. 18.2% for surgery, and a 4.8% rate of major bleeding vs. 20.5% for surgery. The overall major adverse event rate at one year was 4.8% for stenting vs. 25% for surgery.

Carotid stents and associated distal protection devices are expected to become available for clinical use in the U.S. market later this year, following the first FDA panel hearing on carotid artery stents used with distal protection devices which was scheduled for April 21 (see Product Briefs, page 149). The Cordis device, which received a recommendation of approval at that panel meeting, is expected to reach the market first. Other suppliers developing distal protection devices and carotid stents include Boston Scientific (Natick, Massachusetts), with the FilterWire EZ and Carotid Wallstent, now under evaluation in the BEECH trial, and the NexStent from EndoTex Interventional Systems (Cupertino, California), now under evaluation in the CABERNET trial; Abbott Vascular Devices (Redwood City, California), with the NeuroShield and the Xact stent; Medtronic (Minneapolis, Minnesota) with the PercuSurge balloon occlusion system; the Vascular Systems unit of B. Braun Medical (Melsungen, Germany) and Rubicon Medical (Salt Lake City, Utah), with the Rubicon Filter. Rubicon, which is majority-owned by Boston Scientific, plans to launch its device in Europe this month and in the U.S. in 2005. The Rubicon filter has a considerably smaller profile than the Boston Scientific FilterWire (2.4 Fr vs. 3.0 Fr) and is deployed with a single guidewire.

The use of distal protection devices, particularly filters that capture debris released to the bloodstream during a stent procedure, is considered mandatory in carotid stenting procedures, despite the added cost (projected at more than $1,500 for the device based on pricing for existing FDA-approved products used in cardiology), an additional 10 minutes in procedure time to place and remove the filter, and the potential for clogging of the filter if a large amount of debris is released. The benefits, according to Wholey, are a 50% reduction in stroke events vs. stenting performed without distal protection in high-risk patients. Adverse events also are reduced as compared to rates observed in carotid endarterectomy surgery. In spite of the added cost for devices, Wholey estimates that the total procedure cost for carotid stenting is now less than that for surgery, in part because the less-invasive nature of the procedure allows patients to be transferred to a low-level monitoring bed for recovery vs. the neuro intensive care unit.

Interventional radiologists already have developed a considerable level of experience with carotid stenting, as indicated by results of a survey conducted by the SIR showing that 25% of members have some experience with carotid stenting either with or without distal protection. The procedure ranked second after the treatment of peripheral vascular disease in order of priority among the survey respondents. Carotid stenting probably will not, however, be used to treat all patients with carotid stenosis, since advances in medical (drug) therapy have resulted in a 40% reduction in stroke risk in patients with carotid stenosis. Stenting is consequently likely to be limited to patients with severe disease, e.g., those who are symptomatic with a stenosis of greater than 60% or asymptomatic patients with a stenosis of over 50%, who now undergo surgery, as well as high-risk patients who are contra-indicated for surgical treatment. About 75% of carotid endarterectomy procedures are performed on asymptomatic patients in routine practice, according to Buddy Connors, MD, of Baptist Cardiac and Vascular Institute (Miami, Florida). Some 15,000 carotid stent procedures have now been performed worldwide in clinical trials and in practice outside the U.S., according to Wholey, but that number could expand to 200,000 worldwide by 2007; according to experts who presented at the SIR conference, creating a substantial market opportunity. That market would add to the growing market for established applications of peripheral vascular stents, which totaled $533 million in 2003, as shown in Table 1 below.

One factor that will be important in driving expansion of the market is demonstration of the safety and effectiveness of carotid stenting in lower-risk patients than those included in trials such as ARCHeR and SAPPHIRE. In the Carotid Revascularization Endarterectomy vs. Stent Trial (CREST), lower-risk patients are being enrolled, and, based on lead-in data described by Roubin at the SIR conference, the results are encouraging for stenting, with a 2.8% stroke and death rate in the stent group, comparable to event rates for surgery. One group that may not be indicated for stenting, however, is elderly patients over the age of 80. In early data from CREST, those patients have a 12% stroke and death rate vs. only a 1% rate in patients between the ages of 60 and 70, prompting investigators to discontinue the treatment of patients over the age of 80 in the trial. Other factors that will impact adoption include ease of use of the devices, the actual adverse event rates that are observed as use of carotid stenting becomes more widespread, and the availability of training programs for interventional radiologists, vascular surgeons and other specialists who are expected to adopt the procedure.

Regarding the current status of device development for carotid stenting, users are now in agreement that monorail/rapid exchange delivery systems are preferred. In addition, continued improvement in distal protection devices is needed, since most users find that current-generation distal protection devices are difficult to use, requiring meticulous technique to ensure that the device does not move during a procedure, partially negating its benefits. The impact of adequate training and experience with carotid stenting on patient outcome is reflected by data cited by Wholey of a 4% complication rate for procedures performed by physicians who have performed 20 to 50 procedures vs. a rate of 1.56% for those with more than 500 procedures.

Another opportunity for suppliers of vascular stents, as well as of endovascular grafts, lies in the development of devices for use in a wider range of peripheral arteries as well as in visceral applications such as transhepatic intraperitoneal portosystemic shunt (TIPS) procedures. While a wide range of stents is now available for use in larger-diameter vessels such as the iliac arteries, as well as for applications such as renal artery stenting, limited progress has been made in stents for vessels such as the superficial femoral, femoropopliteal and tibial vessels. One supplier, the Intratherapeutics unit of ev3 (Plymouth, Minnesota), has obtained FDA clearance for its IntraCoil stent for use in the femoropopliteal arteries to the tibial bifurcation. The Cordis S.M.A.R.T. stent is an off-label option in the U.S. market, according to experts who discussed peripheral vascular technologies at the SIR conference, and the Symphony stent from Boston Scientific, licensed from NMT Medical (Boston, Massachusetts), is another option in the international market. A new high-flexibility, double-spiral nitinol stent under development by IDev Technologies (Houston, Texas) will offer the capability to be re-deployed and may be available in diameters as small as 2.5 mm for applications in femoropopliteal stenting. Cordis also is continuing to evaluate a version of its drug-eluting stent in the leg vessels, with encouraging six-month patency data (0% restenosis), but issues remain because of the 6% rate of stent fractures observed in the SIROCCO II trial using the device. New small-diameter stents also have been introduced recently (with biliary indications) by Abbott Vascular (the Xpert stent), Boston Scientific (the Sentinol self-expanding stent) and Medtronic (the Racer, a cobalt/chromium alloy device).

A number of suppliers are evaluating endovascular grafts, typically using ePTFE or polyester coverings, for above-the-knee applications, whereas below-knee revascularization continues to be performed using vein grafts or, in 42% of procedures, prosthetic ePTFE grafts. Surgically implanted ePTFE grafts, however, provide lower long-term patency of 59% at four years in below-knee applications, vs. 75% to 80% for vein grafts. Endovascular grafts under development for applications in the lower leg vessels include the Viabahn from W.L. Gore (Flagstaff, Arizona), the aSpire from Vascular Architects (San Jose, California), the Fluency from Bard Peripheral Vascular (Tempe, Arizona) and the JOMED stent-graft from Abbott Vascular. The Viabahn is undergoing FDA review for applications in the superficial femoral arteries, while the aSpire device is cleared in the U.S. for tracheobronchial applications and under investigation for applications in the superficial femoral artery (SFA). Bard's Fluency has been cleared for tracheobronchial applications, but also shows promise for SFA applications. According to Richard Saxon, MD, of San Diego Vascular Institute (Oceanside, California), who discussed endovascular grafts at the SIR meeting, devices such as the Viabahn or Hemobahn, also from W.L. Gore, can provide patency that is equivalent to or somewhat better than that attained with surgical bypass using vein grafts in the femoropopliteal arteries. Cost is an issue, however, since a 15 cm version of the Viabahn is priced at $2,700.

Another device available for the treatment of vascular obstruction in vessels, including the SFA and infrapopliteal arteries, is the PolarCath, developed by CryoVascular Systems (Los Gatos, California) and distributed in the U.S. by Boston Scientific. The PolarCath is a balloon catheter that combines angioplasty with cryotherapy with the goal of reducing restenosis. The device received FDA clearance in 2003. Recent experience with the device, as described by speakers at a Boston Scientific-sponsored satellite symposium at the SIR meeting, has shown more uniform dilatation and less elastic recoil as compared to conventional percutaneous transluminal angioplasty (PTA) using the PolarCath in smaller-diameter arteries in the legs, as well as a much lower rate of dissection (7% vs. 43% with PTA). The dissection rate also compares favorably with that for stents, which is 9%. Patency also is quite attractive, at 82% at nine months vs. 59% for PTA at 12 months, and essentially equivalent to that for stents in similar vessels. The device appears to be particularly effective for the treatment of long, complex lesions in the SFA, since studies have shown that the rate of restenosis does not increase with lesion length. Treatment of in-stent restenosis is another potential application, since in a pilot study in about 15 patients no restenosis has yet been observed. Cost is about $50 more than the cost of a typical peripheral vascular stent.

Another important application for peripheral stents and endovascular grafts that attracted considerable attention at the SIR conference is TIPS and related procedures for the treatment of portal hypertension. A new alternative to the TIPS procedure is under development, designed to provide equivalent clinical results with fewer complications due to hepatic encephalopathy, which occurs in 3% to 7% of patients. The procedure, known as a transvenous extrahepatic portacaval shunt (TEPS), uses a new flanged stent-graft developed by Inavonx (Edmond, Oklahoma). The device consists of a nitinol stent with an ePTFE covering with a flange at each end of the conduit to ensure patency of the ostium of the shunt and to prevent migration. The Inavonx stent-graft was evaluated in an animal study and shown to provide good results in five of six cases, although some stenosis was observed at four weeks post-implant. Some difficulties were encountered in placing the device properly, particularly with avoiding placement in the portacaval space, prompting the researchers to conclude that some refinements of the delivery system are needed.

Existing endovascular grafts, such as the Viatorr from W.L. Gore, already are used in TIPS procedures in Europe and typically provide improved results as compared to bare-metal stents. As discussed by ZJ Haskal, MD, of New York Presbyterian Hospital (New York), recent non-randomized studies of endovascular grafts for TIPS have shown a six-month patency using the Gore Viatorr of 81.4%, vs. 59.6% for the Wallstent, a highly statistically significant difference. Studies with other devices have produced similar results. For example, a study comparing an ePTFE-covered nitinol stent from Taewoong Medical (Seoul, South Korea) with the Wallstent reported one-year patency of 90% for the covered stent vs. 60% for the bare metal stent. Another entry in the market is Atrium Medical (Hudson, New Hampshire), with the Advanta V12 ePTFE covered stent-graft, a product that is available on the European market.

Perhaps the most promising results with endovascular grafts, however, have been obtained in applications in dialysis access. Devices for use in the creation and maintenance of dialysis access address a rapidly growing patient population, as shown in Table 2 below, although the number of synthetic grafts used is not growing because of a continued trend to use native arteriovenous fistulas rather than synthetic grafts. Initial results from an ongoing study using a modified version of the Bard Fluency endovascular graft were reported at the SIR conference that appear very promising, according to D. Vorwerk, MD, of Klinikum Ingolstadt in Germany, representing an advance vs. bare-metal stents as well as other types of endovascular grafts. The Bard device used in the study featured complete coverage of the metal framework with ePTFE, as well as an added flare at the ends. The device may be particularly well suited for treating dissections in dialysis fistulas.

Another new modality for treatment of thrombosed or occluded dialysis grafts that has attracted significant interest among interventional radiologists is the Cutting Balloon, a device developed by Interventional Technologies (San Diego, California), a company acquired by Boston Scientific in February 2001. The Cutting Balloon consists of an angioplasty balloon catheter with small cutting blades attached to the outside of the balloon. The blades produce tiny incisions in the material inside the vessel lumen when the balloon is inflated, in principle providing a more uniform and less traumatic expansion of the vessel. A study involving 340 patients treated at 27 sites using the peripheral Cutting Balloon in thrombosed or failing ePTFE dialysis access grafts was described by T.M. Vesely, MD, of the Mallinckrodt Institute of Radiology (St. Louis, Missouri). Half of the patients were treated with the Cutting Balloon, and half were treated with angioplasty. While there was a slight trend for improved patency at six months follow-up (43.3% for the Cutting Balloon vs. 36.3% for PTA), none of the observed differences were statistically significant. Although the investigators noted that subjects experienced less pain with the Cutting Balloon, there was a slightly higher rate of perforations and dissections (2.9% and 1.7% respectively) in the Cutting Balloon group vs. PTA, where the rate was 0%. The researchers noted, however, that the Cutting Balloon would probably have an advantage only in more difficult cases, such as those that are resistant to a high-pressure balloon. Other new devices for treating thrombosed or stenotic dialysis access grafts and fistulas include the AKonya Eliminator Mechanical Thrombectomy device, now available from IDev Technologies for clearing synthetic grafts and priced at $400; the Atlas large-diameter PTA balloon catheter from Bard Peripheral Vascular; the Prolumen thrombectomy/ embolectomy catheter developed by Rex Medical (Conshocken, Pennsylvania) and now sold by Datascope (Montvale, New Jersey); and the Inner-Lock sheath, used to prevent loss of access when clearing dialysis grafts, also from Rex Medical.

Another growing segment of the dialysis access market is catheters used in hemodialysis procedures. As indicated by the data in Table 2, the use of hemodialysis catheters is growing faster than the number of dialysis patients. The Kendall (Mansfield, Massachusetts) unit of Tyco Healthcare introduced the Tal Palindrome long-term dialysis catheter at the SIR conference, which features a symmetric spiral-Z tip design to avoid recirculation of blood between the venous and arterial ports of the catheter, a common occurrence with conventional sidehole or staggered end-hole designs. An animal study using the Palindrome catheter was described by its developer, MG Tal of Yale University (New Haven, Connecticut), which showed that recirculation was 0% to 3% with the Palindrome vs. rates of up to 18% with other types of dialysis catheters when the dialysis lines are reversed.

Varicose vein treatment interest grows

The less-invasive treatment of varicose veins is attracting considerable interest within the interventional radiology community, sparked by the development of a number of new devices for performing the procedure and growing interest among patients in alternatives to traditional vein-stripping surgery. As shown in Table 3, only 14% of interventional radiologists have performed varicose vein treatment procedures, but 60% of those who are not yet performing vein procedures are interested in doing so. About 145,000 surgical vein stripping procedures are performed in the U.S. and 1 million are performed worldwide according to suppliers of less-invasive varicose vein treatment systems, and less than 10% of treatments are performed using less-invasive methods. Some 42% of Americans over the age of 60 have varicose veins. An estimated 25 million to 40 million people in the U.S. have venous insufficiency, but, as indicated by the surgical procedure data, the proportion treated is very small, in part because of the reluctance to undergo a surgical procedure. According to the leading supplier of endovascular varicose vein therapy devices, VNUS Medical Technology (San Jose, California), about 1 million individuals are seeking treatment in the U.S., but only around 15% elect to undergo surgical stripping. Suppliers of endovascular systems believe the number of procedures will grow substantially as more patients become aware of less invasive options, particularly now that positive long-term data on outcomes is available, along with reimbursement for the procedure. Up to 80% of those with varicose veins are potential candidates for treatment, and suppliers estimate that for 80% of candidates, treatment can be considered medically necessary. Reimbursement for varicose vein treatment is now available for Medicare patients, and many insurers, including some members of the Blue Cross/Blue Shield Association (Chicago, Illinois), now cover the procedure. Charges for varicose vein treatment typically average about $3,000 per leg treated, and range from $2,500 up to $7,000 depending on geographic location of the treatment center and the type of provider.

Suppliers of endovascular varicose vein treatment products are listed in Table 4 below, along with descriptions of their products. VNUS, the only supplier of RF ablation systems, was the first supplier of endovascular systems to enter the market in the U.S., and claims a two-thirds share of the endovascular products market. The company has a strong patent position on RF vein ablation that has prevented the entry of competitors employing the same technology. VNUS has now accumulated data from three multicenter studies comparing RF ablation to surgical stripping showing equivalent outcomes with the less invasive method. Four companies have entered the endovascular segment of the market offering laser-based systems. Dornier Medical Systems (Kennesaw, Georgia), which was one of the first laser system suppliers to enter the U.S. market over three years ago, has placed about 180 Medilas SkinPulse systems and 50 Compact systems in the U.S. The SkinPulse also can be used to treat benign prostatic hypertrophy and to perform colposcopy procedures. Diomed (Andover, Massachusetts), which first entered the U.S. market in 2002, reported EVLT laser product revenues of $9.2 million in 2003, up from $5.6 million in 2002. Diomed has experienced strong demand in 2004 as more payers have begun to cover procedures performed with its EVLT system. Vascular Solutions (Minneapolis, Minnesota) is a new entrant in the market, having launched its Vari-Lase system in January, although the company began supplying laser catheters for use with other laser-based systems in mid-2003. The company has placed about 500 laser systems worldwide to date. Interventional radiologists are the biggest users of the system, followed by phlebologists and dermatologists. Vari-Lase users typically perform between two and 10 procedures per week.

Users are continuing to refine endovascular varicose vein techniques to reduce the pain associated with the procedure and reduce the occurrence of adverse reactions such as bruising of the skin and inflammatory responses. Lowell Kabnick, MD, of the Vein Institute of New Jersey (Morristown, New Jersey), reported on a single-center study comparing vein ablation using a 980 nm laser to an 810 nm device. A total of 51 patients were included in the study, with 60 limbs treated. Although success rates were identical in the two groups, a statistically significant reduction in bruising score was observed in the 980 nm group. There also was a positive, although not significant, trend favoring the effectiveness of the 980 nm laser. Kabnick now is evaluating a 1,320 nm system, since longer wavelengths appear to be associated with reduced side effects. Suppliers are expected to continue to search for technological advantages as the market becomes more crowded and competitive, to help circumvent competition based solely on price.

Growth opportunities in cancer treatment

While considerable opportunity exists in the interventional radiology market for peripheral vascular stents, endovascular grafts and endovascular systems for the treatment of venous disease, many experts predict that oncology products will be one of the largest segments in the IR market of the future. There already is a substantial market for products used in minimally invasive tumor ablation, primarily for radiofrequency ablation (RFA) systems used in the treatment of liver cancer. Another growth segment is products for uterine fibroid embolization, a technique that provides a minimally invasive alternative to hysterectomy for the treatment of pelvic pain. Radiofrequency ablation using RF generators priced at around $30,000 and needle probes priced at $1,000-$2,500 to eradicate tumors are primarily used in the treatment of liver and lung cancer at present. Liver cancer treatment is a rapidly expanding application, due to an epidemic increase in incidence of primary liver cancer as a result of the increasing prevalence of hepatitis C infection, particularly in Asia, as well as a growing number of tumors arising due to metastasis from other primary sites. About 24% of colorectal cancer patients have liver metastases, for example. Worldwide, the annual incidence and mortality for liver cancer is over one million. In the U.S., the number of annual new cases of liver cancer has doubled within the past 10 years to more than 20,000 in 2003. Surgical resection is applicable to only 5% to 15% of cases, creating a growing demand for alternative treatment modalities such as RFA. Other RFA applications showing promise include ablation of metastatic tumors in bone, as well as ablation of kidney tumors. One of the most promising new developments is combination therapy employing RFA along with chemotherapy or external beam radiation to obtain a synergistic effect. In animal studies, cure rates of 60% to 70% have been achieved, whereas clinical cure rates for metastatic colorectal tumors are 5% to 14% at five years. A number of companies have entered the market for RFA ablation products, including Rita Medical Systems (Mountain View, California), Boston Scientific, the Radionics (Burlington, Massachusetts) division of Tyco Healthcare and Vivant Medical (Mountain View, California).

Cryotherapy is an emerging interventional modality that has the advantage of allowing treatment of larger tumor masses as compared to RFA, according to Matthew Callstrom, MD, of the Mayo Clinic (Rochester, Minnesota), who discussed the use of cryotherapy at SIR. That feature stems mainly from the ability to use multiple probes effectively. In contrast, electromagnetic effects limit the ability to use multiple monopolar RFA probes, although bipolar RFA systems now under development may remove that limitation. Visualization of the procedure also is improved with cryotherapy relative to RFA, and the treatment zone boundary can be controlled more precisely, allowing cryotherapy to be used to ablate tumors that are in close proximity to critical organs. Costs for cryotherapy, however, are 1.5 to four times higher than for RFA, in part because multiple probes are often used. Cryotherapy using cryogenically cooled needles is producing promising results in the treatment of prostate and kidney cancer. Suppliers of cryotherapy systems used by interventional radiologists in cancer treatment include Endocare (Irvine, California) and Oncura (Plymouth Meeting, Pennsylvania).

Another interventional technique that is attracting interest for targeted delivery of cancer therapy is chemical ablation, according to Timothy Clark, MD, of the Hospital of the University of Pennsylvania (Philadelphia, Pennsylvania). The method uses drug-delivery probes such as the Quadra-Fuse multi-pronged injection needle from Rex Medical. Clark described the use of acetic acid ablation for the treatment of liver tumors in studies that demonstrated survival rates of 92% at two years. Acetic acid is a preferred agent for chemical ablation because it not only ablates tumor tissue but also produces acidosis at the tumor site that helps to prevent spreading of malignant cells.

The use of microparticles in cancer therapy is another growing application for interventional radiology. As discussed by R. Salem, MD, of Northwestern University (Evanston, Illinois), at the SIR conference, radioactive microspheres (Theraspheres) from MDS Nordion (Ottawa, Ontario) have shown considerable promise in the treatment of metastatic colorectal tumors in the liver. The use of microparticles delivered by selective catheterization, a procedure known as radiation segmentectomy, is advantageous in the liver because of the low tolerance of that organ to radiation. By selectively infusing Theraspheres containing Yttrium-90, doses can be delivered to a tumor that are as much as 100 times greater than those causing adverse effects on the liver when external beam radiation is used. In one study, most patients could be treated on an outpatient basis, and a metabolic response was observed in 83% of patients. Salem now advocates conducting trials combining Therasphere treatment with systemic chemotherapy for the treatment of metastatic colorectal cancer. Other suppliers of particle-based radiotherapy products include Sirtex Medical (North Ryde, Australia), Theragenics (Buford, Georgia) and North American Scientific (Chatsworth, California).

Critical Care Innovations (Edgewood, Kentucky) is developing a next-generation technology for cancer treatment that uses magnetically activated drug release at a tumor site. The company has signed an agreement with the National Aeronautics and Space Administration (NASA; Washington) to develop commercial applications for microencapsulation technology, with the proviso of being able to obtain a license to the NASA multilaminate microcapsule technology. The company is evaluating the use of drug-containing microparticles that dissolve in the presence of a magnetic field as a highly targeted modality for chemotherapy delivery. Another technology that employs magnetic control of drug delivery, the MagneTarg drug delivery system, is under development by FeRx (San Diego, California). The system uses drug-loaded Magnetic Targeted Carriers which are microparticles composed of metallic iron and activated carbon, and which serve as delivery vehicles that allow highly selective administration of chemotherapy at a tumor site. The particles are injected at the tumor site through a super-selective catheter inserted via the femoral artery. A small external magnet is used to extravasate the arterially injected particles into the tumor tissue, where they are retained after the magnet is removed. The magnet is applied for only 15 minutes, and accurate delivery can easily be verified via magnetic resonance imaging of the iron-containing particles. The MagneTarg system is now in Phase III clinical trials for the treatment of unresectable liver cancer.