Vascular Brachytherapy and the Strontium90 Vascular Brachytherapy System

Vascular brachytherapy, the delivery of a single dose of a radioactive isotope directly inside the target area of the coronary artery after balloon angioplasty, is the only clinically proven therapy and is the standard of care for patients with in-stent restenosis. Over the last several years, vascular brachytherapy has been widely studied with several multicenter, randomized trials, registries and many single center experiences with several different systems and isotopes. The Strontium90 vascular brachytherapy system (Beta-Cath™ System, Novoste Corporation, Norcross, Georgia), the first vascular brachytherapy system to be approved for use outside the United States and the first beta vascular brachytherapy system to be approved in the United States, has been researched in the Beta Energy Restenosis Trial (BERT), Beta-Cath Trial, Stents and Radiation Therapy Trial (START), Stents and Radiation Therapy Trial 40 (START 40) and European Marketing Surveillance Registry with the Novoste Beta-Cath System (RENO). All of these trials demonstrated clinical statistical significance in the treatment of in-stent restenosis when compared to a placebo group. These trials reported 38–66% improvement in angiographic restenosis rates as compared to placebo.1–3 Recently, several large US cath labs have reported their real world results with the Strontium90 vascular brachytherapy system of clinical target revascularization rates as low as 4%.4 We have had a similar experience at Swedish Medical Center where we have treated over 400 patients with the Strontium90 vascular brachytherapy system and are in the process of collecting our follow-up data. Vascular Brachytherapy with the Strontium90 Vascular Brachytherapy System The Strontium90 vascular brachytherapy system was designed specifically for use in the cath lab and utilizes a patented hydraulic system to deliver the Strontium90 radiation source train into the coronary artery. Strontium90 is an ideal isotope for vascular brachytherapy and the cath lab because it is easy to shield, there is no additional radiation exposure to the cath lab staff and the isotope’s 28.8 year half-life means that the treatment times remain consistent from day-to-day use. The multiple radiation source trains (30 mm, 40 mm and 60 mm) allow appropriate radiation coverage of the entire injured area to ensure good clinical outcomes. The b-Rail™ 3.5F Delivery Catheter is the smallest catheter available and is designed to allow use in a 6F guide catheter and to allow access to distal anatomy. The Strontium90 vascular brachytherapy system is comprised of the b-Rail 3.5F Delivery Catheter, the Transfer Device (which stores, shields and delivers the radiation source train) and the Strontium90 Jacketed Radiation Source Train. Once the in-stent restenosis area has been dilated (via balloon angioplasty, cutting balloon, etc.), the delivery catheter, a distal monorail, is inserted onto the guide wire and advanced to the treatment area by the cardiologist. The treatment end of the catheter will be centered in the area that was injured allowing 5–10 mm margins of radiation coverage on both sides of the injured area. This can easily be accomplished by using the radiopaque markers on the indicator of source train (IST). Once the catheter is documented to be in correct placement, the cardiologist will use the IST to document catheter lumen integrity by retracting and re-advancing the IST two to three times and assessing smooth catheter movement. Once the lumen integrity is determined, the IST is completely removed from the delivery catheter. The proximal end of the delivery catheter is then attached to the transfer device and locked in place. After the transfer device is attached to the delivery catheter, the system is ready to send the radioactive sources to the end of the delivery catheter. Delivery of the radioactive source train is done by a licensed individual (a radiation oncologist), or in some states, the radiation source train can be delivered by a designated individual (which could be a cardiologist or medical physicist) under the supervision of a licensed individual (a radiation oncologist). At Swedish, the radiation oncologist delivers the radiation source train and will send the radiation source train to the end of the delivery catheter via the water hydraulic system. The radiation source train will then dwell at the treatment area for approximately three minutes and then be returned to the transfer device via the water hydraulic system. Then the entire system is removed from the patient, and the procedure is complete. The entire vascular brachytherapy procedure adds approximately 5–10 minutes to the PCI. Advantages of the Strontium90 Vascular Brachytherapy System The low catheter profile of the Strontium90 vascular brachytherapy system and its flexibility provide the ability to negotiate multiple vessel types and utilize the multiple radiation source train lengths (30 mm, 40 mm and 60 mm) to ensure good clinical outcomes. The b-Rail 3.5F Delivery Catheter is the smallest vascular brachytherapy catheter on the market and easily accesses distal tortuous anatomy. The jacketed radiation source train also is a unique feature that allows great flexibility and trackability inside the delivery catheter and through the patient’s anatomy. We rarely have experienced any situation where we were unable to position the catheter or deliver the radiation source train due to the patient’s anatomy. Also, treatment times are consistent from day to day, minimizing any disruption to cath lab scheduling and patient flow. Our radiation oncologists like the flexibility that the Strontium90 vascular brachytherapy system offers them, allowing them to choose to be in or out of the sterile field while delivering the radiation source train, and the multiple radiation source train lengths, allowing optimal lesion coverage and consistent dose distribution. The option for the radiation oncologist to be out of the sterile field simplifies the setup process and minimizes the time that the radiation oncologist is in the cath lab and away from his office and patients. Additionally, the radiation oncologists like working with Strontium90 because of the localized delivery of the radiation dose—almost all of the radiation dose is delivered to the target tissue with very little dose to nontarget tissues—as compared to a gamma isotope like Ir192 where healthy tissue and surrounding organs get a large dose of radiation during a vascular brachytherapy procedure. Our medical physicists like the stability of the Strontium90 isotope with a half-life of 28.8 years, which means that they only have to service the system every six months, and there is no change in the dwell times from day to day. They also like the jacketed radiation source train because of its easy visibility and its ability to reach the treatment area where other vascular brachytherapy radiation sources often cannot reach. Vascular Brachytherapy Patient Selection We are fortunate to be able to offer vascular brachytherapy almost every morning at our institution, so we try to treat all of our in-stent restenosis patients with vascular brachytherapy. Once we have a diagnosis of in-stent restenosis, we can then proceed with a cutting balloon to dilate the in-stent restenosis to ensure that we minimize the balloon injury and then follow with vascular brachytherapy. This combination therapy has led to our high success rate when treating patients with in-stent restenosis. We also have had good clinical outcomes treating saphenous vein graft (SVG) in-stent restenosis lesions, bifurcation in-stent restenosis lesions and renal in-stent restenosis lesions. Since these are off-label indications, we have worked closely with our radiation oncologist and medical physicist to develop a treatment strategy for these patients and pre-plan our dosimetry prior to delivering vascular brachytherapy. In our screening process for vascular brachytherapy candidates, we do not treat patients with a known anticoagulant and/or antiplatelet allergy with vascular brachytherapy. We also have not treated any patients with unprotected left main disease. Use of IIB/IIIAs with Vascular Brachytherapy Patients We rarely use IIB/IIIAs with vascular brachytherapy, since the lesions rarely fit the criteria of an acute coronary syndrome and since the procedures are infrequently associated with complications. Use of Antiplatelet Therapy At Swedish, we limit the implantation of a new stent when we plan to deliver vascular brachytherapy, but if unavoidable, due to a dissection, we implant the new stent prior to the vascular brachytherapy treatment and ensure that we adequately cover the entire treated area with the radiation source train. We also place these patients on prolonged antiplatelet therapy (~12 months) to minimize the risk of late stent thromboses. We have not had any incidences of late stent thromboses in patients that have followed this treatment regimen. For those patients treated with vascular brachytherapy without a new stent implanted, we prescribe six months of antiplatelet therapy, and we have not seen any incidence of late stent thromboses in these patients. Future of Vascular Brachytherapy Our experience with vascular brachytherapy has been very positive with a clinical success rate of ~95%. Vascular brachytherapy is also a cost-effective therapy for in-stent restenosis with established physician and hospital reimbursement. While the incidence of in-stent restenosis will be significantly reduced with the use of drug eluting stents, there still will be a group of patients with in-stent restenosis that will benefit from vascular brachytherapy. We have already treated one patient with a failed drug eluting stent with vascular brachytherapy. We currently plan to continue to use vascular brachytherapy for the treatment of all patients with in-stent restenosis—even in the era of drug eluting stents—since drug eluting stents are not approved for the treatment of in-stent restenosis. Clinical data to date for the treatment of in-stent restenosis with drug eluting stents have been reported on 71 patients, and the results have been mixed.5–7 Additionally, clinical trials are currently researching the clinical effectiveness of vascular brachytherapy for the prevention and/or the treatment of restenosis in peripheral artery disease and for the treatment of venous outflow restenosis of arterial venous access grafts in hemodialysis patients. Initial data in the treatment of peripheral artery disease utilizing gamma vascular brachytherapy to prevent restenosis in superficial femoral artery lesions have demonstrated superiority over balloon angioplasty and were associated with high patency rates of nearly 75% at one year.8,9 A modified Strontium90 vascular brachytherapy system (Corona™ System, Novoste Corporation, Norcross, Georgia), which utilizes a centering catheter and the same transfer device, is currently being used to research the treatment of in-stent restenosis in the superficial femoral artery in the MOre patency with Beta In the Lower Extremity (MOBILE) trial. The same system is also being used to research the treatment of venous outflow restenosis of arterial venous access grafts in hemodialysis patients in the Beta Radiation for treatment of Arterial-Venous graft Outflow (BRAVO) trial. We expect to see clinical results presented on both of these trials in 2004. Another interesting application for vascular brachytherapy is the treatment of failed drug eluting stents. Efforts are underway to determine if vascular brachytherapy is as clinically effective in the treatment of drug eluting stent in-stent restenosis as it has been in the treatment of bare metal stent in-stent restenosis. Failed drug eluting stent patients will be a challenging group of patients to manage, and we are optimistic that vascular brachytherapy will be an effective treatment option for this patient population. Conclusion Vascular brachytherapy is the only proven treatment for in-stent restenosis, and our experience with vascular brachytherapy has been very positive with a clinical success rate of ~95%. It is an easy therapy to use and works well in patients with in-stent restenosis. The Strontium90 vascular brachytherapy system offers several unique features (smallest delivery catheter, 6F guide catheter compatibility and catheter/radiation source train flexibility to cross tortuous anatomy) that improve patient procedural success, and its ease of use features (long half-life, consistent treatment times and ability to use in or out of the sterile field) help streamline the vascular brachytherapy procedure in our cath lab. Logistical challenges can be overcome by maintaining open communication between the vascular brachytherapy team members (cardiologist, radiation oncologist, medical physicist and cath lab staff). It is important to arrange case coverage schedules, to plan for “off-vascular brachytherapy days” case coverage options and to communicate patient clinical outcomes so that the team understands the value that vascular brachytherapy is providing to the patients. We are committed to maintaining our vascular brachytherapy program at Swedish because we believe that vascular brachytherapy is and will remain a valuable clinical therapy for the treatment of coronary in-stent restenosis. We are also excited about the potential to expand the clinical applications of vascular brachytherapy into peripheral artery disease and arterial venous access grafts and the associated patient benefits.

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