Brachytherapy: hot or not.

Abstract

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 sixmonth 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 instent 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 tech