| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Editorial |
1 From the Department of Radiology, University of Arkansas for Medical Sciences, 4301 W Markham St, Mail Slot 556, Little Rock, AR 72205. Received May 1, 2002; accepted May 3. Address correspondence to T.C.M. (e-mail: mccowantimothyc@uams.edu).
Index terms: Arteries, radiation • Arteries, restenosis, 92.44 • Arteries, stenosis or obstruction, 92.72, 92.721 • Arteries, transluminal angioplasty, 92.1281, 92.1286, 92.454 • Editorials
Many in modern medical practice now embrace percutaneous transluminal angioplasty as a valid and important treatment option for occlusive vascular disease, both in coronary and peripheral arterial systems (1). Despite excellent overall technical and clinical success rates, immediate and long-term failures pose a substantial problem for this minimally invasive therapy. Interventionalists have countered immediate complications and failures (eg, difficult to cross lesions, dissection, elastic recoil, acute thrombosis) with improved guide wires and balloons, variety of stents, and antithrombotic pharmacologic agents. Combating long-term failure, predominantly restenosis, remains more of a challenge.
Results of the study performed by Krueger et al (2) reported in this issue of Radiology add important support for the use of endovascular irradiation (brachytherapy) to prevent vascular restenosis after percutaneous therapy. In a prospective controlled study, the researchers randomized thirty patients to receive endovascular irradiation with an iridium 192 source or a placebo after percutaneous transluminal angioplasty of femoropopliteal atherosclerotic lesions. As opposed to most other studies, Krueger et al treated only de novo atherosclerotic disease with percutaneous angioplasty without stent placement. Twenty-two patients at six-month and 12 patients at 1-year follow-up underwent arteriography. The irradiation group showed a statistically significant change in the degree of stenosis after angioplasty compared with the nonirradiation group at both 6 months (-14.7% ± 20.8 vs 37.7% ± 27.3, respectively; P = .001) and 12 months (-9.5% ± 34.5 vs 45.5% ± 40.7, respectively; P = .03). In other words, the lumen at the angioplasty site continued to enlarge in the irradiation group compared with an actual luminal decrease in the nonirradiation group.
Complications were minimal but included one acute thrombosis in the irradiation group that was probably secondary to vessel injury during catheter manipulation. The authors did encounter restenosis outside the angioplasty site but within the irradiated segment of the vessel in three cases (not significantly different from the placebo segments). The authors also obtained and analyzed a variety of other clinical, imaging, and physiologic parameters, such as patient interviews, duplex ultrasonography, treadmill examinations, and ankle-brachial index. Most of these parameters showed a trend, though not statistically significant despite differences in restenosis rates, toward benefit in the irradiation group. The relatively small number of patients in this study may have made differences in the clinical outcome undetectable.
These study findings compare favorably with brachytherapy results of the coronary circulation (most treating in-stent restenosis) and few other reports of irradiation during peripheral femoropopliteal interventions (3). Liermann et al (4) published an 84% patency rate at 7.5 years for irradiated peripheral arteries (nonrandomized study). Minar et al (5,6) initially reported less success with long femoropopliteal lesions (nonrandomized study) but recently documented a reduction in restenosis from 53.7% to 28.3% at 6 months in a prospective randomized study (mixture of de novo and restenotic lesions, limited angiographic follow-up). Waksman et al (7) reported a 17.2% restenosis rate at 6 months (angiographically) and 13.3% rate (clinically) at 12 months in the irradiated superficial femoral artery (nonrandomized study).
One or both of two pathologic processes generally contribute to restenosis after endovascular therapy. Recurrent or progressive atherosclerotic disease may cause luminal occlusion commonly 1 or more years after intervention. Neointimal hyperplasia occurs sooner, frequently in less than 1 year, and can also lead to narrowing. The pathologic process of intimal cell proliferation, mediated and characterized by activation of blood agents such as platelets and by migration of smooth muscle cells in the media and adventitia to the luminal surface, probably represents an exuberant reaction to vessel injury (such as that from angioplasty). The localized accumulation of these cells and the complex matrix they produce lead to a compromise of the vessel lumen.
Of the different strategies to limit neointimal hyperplasia, cellular suppression with ionizing radiation has shown promise both experimentally and in clinical trials. Human studies of the coronary and peripheral vascular systems have usually used endoluminal transcatheter delivery of a radiation source, either a beta (such as phosphorus 32 or samarium 153) or a gamma-ray (such as iridium 192) emitter (8,9). This technique, however, has limitations and drawbacks. The use of these highly radioactive sources may expose patients, operating physicians, and technical staff to potentially significant doses of radiation. Additionally, the technique requires the collaboration of radiation therapists and, especially, physicists for the dosimetry.
Methods for the delivery of the radiation source to the target site vary; a carrier wire inserted through a catheter or a fluid source injected into an angioplasty balloon are mostly used (10,11). The carrier wire requires proper placement in the vessel lumen (usually with a centering balloon) so that inordinate radiation exposure does not occur on one wall, while the opposite wall receives a minimal or subtherapeutic dose. Additional manipulations and prolonged retention of catheters and wires in the vessel lumen may increase the risk of acute thrombosis or vascular injury, such as dissection. Radiation doses of 6–30 Gy (1–3 mm into the vessel wall) in most studies seemed effective and safe. Research findings, however, have yet to elucidate the optimal method for delivering the appropriate radiation dose to frequently heterogeneous lesions or to characterize exactly which part of the vessel wall needs irradiation for the best suppression of restenosis.
We also do not know the long-term consequences of this therapy. Although induction of neoplasia remains a theoretic possibility, most patients with severe atherosclerotic vascular disease probably have limited enough life expectancies to minimize this concern. Radiation injury to the vessel wall could lead to occlusive vasculitis, formation of aneurysms, or other untoward effects. Increased intimal proliferation may actually occur at the edges of the treated segments, the so-called candy-wrapper effect (12). Authors of some studies suggest that intraluminal radiation, especially in segments with stents, may predispose to vessel thrombosis by reducing the intimal response that would normally cover the metal components and leaving exposed elements or unhealed tissue conducive to thrombus formation (13). The ultimate costs of setting up such brachytherapy equipment and programs in clinical practice are unknown but probably not insignificant.
Does brachytherapy have a role in the treatment or prevention of restenosis following endoluminal therapy for vascular disease? Compelling experimental and clinical evidence demonstrate that endoluminal irradiation can suppress the local cellular mechanisms that lead to neointimal hyperplasia and possibly even limit recurrent or progressive atherosclerotic disease, both in de novo treatment of vascular disease and in therapy of previously failed interventions (eg, in-stent restenosis). Uncertainty of the ultimate clinical use of brachytherapy, however, clouds its future. Current brachytherapy techniques, although improving, seem cumbersome and not without some increased risk. The unknown cost-to-benefit ratio, unproven long-term effectiveness, and notable logistic difficulties, compared with other treatment options, may slow or lessen widespread adoption.
Stiffest competition for brachytherapy will probably come from either (a) enhanced mechanical devices such as balloons (perhaps for gene therapy) or stents (perhaps drug-eluting) that offer greater simplicity to use and deploy or (b) improved systemic pharmacologic therapy that will deal globally with the patient’s vascular pathologic processes, whether those due to neointimal hyperplasia or those due to atherosclerosis. Not every patient develops recurrent stenosis after endoluminal therapy. Delineation of those at highest risk for restenosis and determination of the most appropriate interventions for prevention and treatment remain challenging but rewarding research endeavors.
FOOTNOTES
See also the article by Krueger et al in this issue.
REFERENCES
Related Article
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| RADIOLOGY | RADIOGRAPHICS | RSNA JOURNALS ONLINE |
