Too Late! Too Complex! But!

Is There a Need for a Technology that Will Promote Positive Remodeling and Mild Plaque Increase? “Favorable vessel remodeling observed in this study is consistent with the result of the previous gamma radiation study noted above,¹ as well as those at the non-stented target segment treated with beta radiation.^2–5 On the other hand, the exact reasons for the mild plaque mass increase after high-dose radiation exposure at the normal, non-injured segments remain unclear.” — Kaneda et al.⁶What is Geographic Miss⁷? In radiotherapy, geographic miss (GM) represents an area planned in the treatment, but which has not received the prescribed dose; it is often related to inadequate margins, causing local failure. In vascular brachytherapy, GM refers to an arterial portion that has undergone injury during the interventional procedure, but has not received the prescribed dose of radiation. This includes vessel zones receiving either no radiation, or a dose less than that prescribed, and may be related to an inadequate radiation margin, potentially leading to local failure. Low-dose radiation associated with vascular injury has been reported to result in increased restenosis, potentially due to gene stimulation through signal transduction, with generation of cytokines and growth factors promoting proliferation, inflammation, extracellular matrix secretion, tissue repair, fibrosis and negative vascular remodeling. GM has emerged as a contributing factor that may have an impact on the clinical results following vascular brachytherapy. However, GM can be eliminated through education, training and awareness of the need for meticulous documentation of injury length (recording each step of the intervention); proper radiation source positioning; and the availability of appropriate-length radiation delivery devices, for the treatment of “no disease” segments with the prescribed dose of radiation. Is Beta Radiation Safe Over the Long Term? The START post-approval studies were intended to evaluate the long-term safety and efficacy of the Beta-Cath™ System in patients who were enrolled in the START and START 40/20 trials for the treatment of in-stent restenosis of native coronary arteries. Vascular brachytherapy using Sr-90 reduced the primary clinical endpoint of target vessel revascularization by 34% at 8 months, and by 24% (p = 0.025) at 2 years in patients undergoing treatment for in-stent restenosis. The absence of safety issues at 2 years (in spite of short antiplatelet therapy regimens in the new stent populations, only 26% had > 60 days, and only 3% > 90 days) was recognized.⁸ The follow up demonstrated continued significance in favor of the Sr-90 group for MACE through 3 and nearly 4 years (p = 0.06), and showed continued significance in favor of the Sr-90 group for TVR rates at 3- and 4-year follow up, but by 5 years, while statistical significance was not reached, the results were numerically in favor of Sr-90.⁹How to Use Positive Vessel Remodeling? Positive vessel remodeling has been recognized in numerous studies, and seems to be a characteristic of a full dose of radiation on non-stented vessels!^3,6,10 Recent studies have shown the benefit of drug-eluting stents over radiation in the treatment of in-stent restenosis, or at least the noninferiority of the newer devices, putting to rest the argument favoring beta radiation treatment for in-stent restenosis in lesions of short or medium length. Can beta radiation be used instead to “stabilize” vulnerable plaque, if plaque can thicken and vessels can enlarge? To be continued! Raoul Bonan, MD Montreal Heart Institute Montréal, Québec E-mail: raoul.bonan@mmic.net

References 1. Ahmed JM, Mintz GS, Waksman R, et al. Safety of intracoronary gamma-radiation on uninjured reference segments during the first 6 months after treatment of in-stent restenosis: A serial intravascular ultrasound study. Circulation 2000;101:2227–2230. 2. Kozuma K, Costa MA, Sabate M, et al. Three-dimensional intravascular ultrasound assessment of the noninjured edges of beta-irradiated coronary segments. Circulation 2000;102:1484–1489. 3. Meerkin D, Tardif JC, Bonan R, et al. Effects of intracoronary b-radiation therapy after coronary angioplasty: An intravascular ultrasound study. Circulation 1999;99:1660–1665. 4. Sabate M, Serruys PW, van der Giessen WJ, et al. Geometric vascular remodeling after balloon angioplasty and beta- radiation therapy: A three-dimensional intravascular ultrasound study. Circulation 1999;100:1182–1188. 5. Sabate M, Marijnissen JP, Carlier SG, et al. Residual plaque burden, delivered dose, and tissue composition predict 6-month outcome after balloon angioplasty and beta-radiation therapy. Circulation 2000;101:2472–2477. 6 Kaneda H, Honda Y, Morino Y, et al. Safety of beta radiation exposure to the non-target segment: An intravascular ultrasound dosimetric analysis. J Invasive Cardiol 2006;18:309–312. 7. Bonan R, Meerkin D, Bertrand OF. Geographic miss: What is it? J Invasive Cardiol 1999;11:749–756. 8 . Silber S, Popma JJ, Bonan R, et al. Two-year clinical follow-up of 90Sr/90Y ß-radiation versus placebo-control for the treatment of in-stent restenosis. Am Heart J 2005;149:689–694. 9 . Personal communication. 10. Verin V, Popowski Y, De Bruyne B, et al. Endoluminal beta-radiation therapy for prevention of coronary restenosis after balloon angioplasty. N Engl J Med 2001;344:243–249.