47 invited The Cinderella of intervention cardiology: endovascular brachytherapy or drug-eluting stents

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Saturday, 3 April 2004 Symposium/Proffered Papers Disorders of the vascular system 44 invited The advantages of using radiotherapy to treat peripheral vascular disease

E. Minar General Hospital Vienna, Angiology, Wien, Austria Endovascular brachytherapy (EBT) is a promising technology with the potential to reduce the restenosis rate. It has been approved already by the FDA for the treatment of coronary instent restenosis, due to the positive results of many clinical studies. Otherwise, until now there are only few trials in peripheral arteries. The results available until now from these trials are very promising concerning the possibility of a significant and clinically relevant reduction of restenosis after femoropopliteal angioplasty. However, due to the limited clinical experience we cannot generally recommend EBT after peripheral interventions at this time despite the positive results obtained in most of the peripheral trials. The PARIS-trial- which has been initiated in the USA to get FDA-approval for peripheral EBT- was the only trial which could not demonstrate an advantage of EBT concerning prophylaxis of restenosis. EBT has been shown to be a safe treatment modality. The only clinically relevant problem is the occurence of late sudden thrombotic occlusion after stenting and EBT. This requires optimization of the antithrombotic regimen. If gamma-radiation is used- as has been done in most of the peripheral EBT-trialsthe patients have to be transported to the brachytherapy unit after the intervention due to the special shielding requirements for such high activity sources. Recent studies using betasources have been started allowing the EBT to be done in the catheter laboratory. The next years will demonstrate the ultimate role of EBT in comparison to the rapidly evolving field of drug-eluting stents. Considering economic aspects, EBT is a relatively cheap treatment modality. Furthermore there will remain niche indications where implantation of stents should be avoided. A further indication will be the occurrence of instentrestenosis after implantation of drug-eluting stents. In the near future studies comparing peripheral EBT with implantation of drug-eluting stents should be started. 45 oral

Effect of Probucol and EVBT on restenosis after PTA of femoropopliteal arteries: a randomized multicenter trial

R.H. Greiner1, F. Mahlef , C. Landmann3, U. L(~tolf~,J. Bernief , A. Gallino5 I University Bem, Radiation Oncology, Bern, Switzerland 2University Bern, Angiology, Bern, Switzerland ~Kantonsspital, Radiation Oncology, Basel Switzerland 4University Zuerich, Radiation Oncology, ZDrich, SWitzerland SOspedale San Giovanni, Radiation Oncology Angiology, Bellinzona, Switzerland Objective: To evaluate the prevention effect of endovascular brachytherapy and the antioxidant probucol on the incidence of restenosis after PTA of femoro-popliteal arteries. Material and Methods: 335 pts with claudicatio Rutherford 2/3 were randomized according to a 2x2 factorial design into 4 groups: EVBT, Probucol, EVBT+Probucol and placebo group. EVBT dose was 14 Gy applied from a non-centering endoluminal catheter at a depth of the radius of the dilated vessel plus 2mm. Probucol (1 g/d) or placebo given according to a randomized, double-blinded protocol was started one month before up to 6 month after PTA; all pts received aspirin 100

mg/d) Primary endpoint was restenosis defined as > 50% reduction of diameter as detected by Duplex ultrasound 6 months after PTA. Results: The actuarial restenosis rate at 6 months f-up was 17% in the group of patients undergoing EVBT, 20% in patients with EVBT + Probucol, 27% in those treated with Probucol and 42% in the control group (p<0.01 for both EVBT vs no EVBT and Probucol vs no Probucol). The rates of pts free of claudicatio at 6mo were 79% in the EVBT group, 74% in the EVBT+Probucol, 78% in the Probucol and 56% in the control group (p<0.01 for EVBT vs no EVBT). Late thrombotic occlusion occurred in 5%, exclusive, in pts. treated with EVBT after stent implantation. Conclusion: EVBT and Probucol after PTA reduce the restenosis rate by 50% and by 23%, respectively. EVBT also improves symptoms and reduces the need of reinterventions. 46 oral External beam irradiation for the prevention of peripheral arteries re-stenosis

D. Kardamakis, P. Zambakis, D. Siamblis, Z. Malatara, T. Skouras, C. Kalogeropoulou, D. Karnabatidis, J. Dimopoulos University of Patras Medical School, Department of Radiotherapy, Patras, Greece Aim of the study: to evaluate the feasibility and efficacy of external beam irradiation (EBI) for the prevention of neointimal hyperplasia, after percutaneous transluminal angioplasty (PTA) and stent placement of the superficial femoral artery. Material and methods: a total of 60 patients with the diagnosis of superficial femoral artery stenoses or occlusions due to peripheral arterial obstructive disease, underwent PTA and implantation of an uncovered self-expandable stent. After the procedure, patients were randomised either to EBI (6 MV photons, total dose 24 Gy in 6 fractions), or no radiation therapy. Results: radiation therapy was technically feasible in all patients, without serious radiation related side effects. Overall, a statistically significant difference (p=0.04) was observed in stenosis categories between the two groups at 6 months followup. Significantly more patients in control group presented with stenosis greater or equal than 70% (EBI group 30%; control group 66.7%; p=O.009). This had as a consequence significantly lower re-intervention rates among the patients of the EBI group (17% versus 47%; p=0.025). There was also a statistically significant difference in the percentage of stenosis between the lumen and the edge of the stent in the EBI group (p<0.05). The sites of restenoses in the control group were observed in the whole lumen of the stent and not only at the stent edges. Conclusions: it is our belief that EBI is a feasible, safe and effective method for the prevention of neoinitmal hyperplasia at the superficial femoral artery. Further studies are deemed necessary to optimize the radiation dose and number of fractions. 47 invited The Cinderella of intervention cardiology: endovascular brachytherapy or drug-eluting stents

P. Levendaq Erasmus MC, Rotterdam, The Netherlands The application of ionizing radiation as therapeutic option for restenosis after vessel injury has generated much interest over the last decennium. It is believed to reduce neo-intimal formation and negative vessel remodelling. Following balloon angioplasty (PTCA) and implantation of bare metal stents, endovascular

Symposium/Proffered Papers

Saturday, 3 April 2004

brachytherapy (EVBT) seems to be the third revolution in the field of intervention cardiology, reducing the re-stenosis rate with about 30%. As it seems, the fealous sisters of Cinderella are the believers in endovascular brachytherapy for prophylaxis of re-stenosis after coronary artery disease, and so does Erich Minar's femoropopliteal angioplasty (PTA) group. The one and only Cinderella that is talked about today is Queen DES; whether she will ultimately marry her prince, however, remains to be seen. The moral of this presentation/debate is, after reviewing relevant clinical data, "don't bury EVBT alive as yet~', nor for coronary arteries, neither for the femorals, let us be prudent and let time has its course first ...... 48 invited Intracoronary brachytherapy: prevention of restenosis

not effective for primary

G. Sianos Eramus Medical Centre, Rotterdam, The Netherlands Many randomised trials have proven the effectiveness for the treatment of in-stent restenosis (secondary prevention of restenosis). Many studies investigated its role for the treatment of de-novo lesions (primary prevention of restenosis). In the PREVENT trial (70% de novo lesions) a small placebo controlled, dose finding study the clinical and angiographic outcome was better in the irradiated patients. However, edge restenosis reduced the overall clinical benefit of radiotherapy. A 10% incidence of late vessel occlusion was also reported with one month of double anti-platelet therapy In the BRIE registry 149 patients received 14Gy of beta radiation. Restenosis and MACE rates were 34%. In this trial the problem of edge restenosis was related to the occurrence of geographical miss. A 5.7% late vessel occlusion rate was reported and the prolongation of antiplatelet treatment reduced its incidence. Patients that received a new stent in combination with radiation had worse clinical and angiographic outcomes compared to 10atients treated with balloon angioplasty and radiotherapy. The same was observed during the European Dose Finding study the other major trial for de-novo lesions. The Beta-Cath trial was the largest randomized trial of betaradiation and stenting in de novo lesions (951 patients). It failed to show any difference in the primary end point in the radiation arm compared to control. The late vessel thrombosis, edge restenosis and the incompatibility of radiation with the use of stents for de novo lesions were the main lessons learned from this negative. The BRIDGE study, a multicenter, randomized controlled clinical trial, was the last attempt to find out if there is any role of brachytherapy for the treatment of de-novo lesions in combination with stenting by optimizing all the peri-procedural parameters (use of lib/Ilia blockers, direct stenting, adequate radiation coverage, avoidance of edge damage, source centering, IVUS guided dosimetry and continuation of a dual antiplatelet regimen for one year). The intra-stent late luminal loss (primary endpoint) at 6 months was 0.43 mm in the treated group and 0.84 mm in the control group. However, in the irradiated group there were 6 late occlusions as well as 8 restenosis outside the stented and peri-stented area, at the falloff dose edges of the irradiated area, resulting in higher target vessel revascularization and MACE rates. Following the results of these trials we can safely conclude that Intracoronary brachytherapy: not effective for primary prevention of restenosis.

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49 invited Radiation for failing AV dialysis grafts-results of the bravo-1 (beta radiation for treatment of arterio-venous graft outflow) randomized trial

I. Crocker ~ S. Misra 2, P. Roy-Chaudhur7 ~Emory University, Radiation Oncology, Atlanta, U.S.A. 2Mayo Clinic, Radiology, Rochester, U.S.A. 3U. of Cincinnati, Nephrology, Cincinnati, U.S.A. Background: Approximately 200,000 patients undergo regular hemodialysis in the United States each year. Many of them are dependent on AV dialysis grafts to provide vascular access. These grafts are prone to stenosis requiring angioplasty or surgical revision. The BRAVO trial was a triple masked randomized trial to assess the utility of beta radiation in preventing restenosis in patients with failing grafts. Materials and Methods: The BRAVO-1 Trial planned to enrol 215 patients from 30 centers with half randomized to receive endovascular brachytherapy post angioplasty. The trial was closed after enrolment of 25 patients due to poor accrual. This report documents the 6 month follow-up of this limited cohort. Results: Treatment was delivered successfully in all 25 patients. At 6 months angiographic restenosis had occurred in 11/11 controls versus 6/12 in the irradiated group. With further intervention 11/12 of irradiated grafts were patent versus 10/11 non-irradiated grafts. No serious adverse events related to brachytherapy treatment were identified. Conclusions: Vascular brachytherapy is feasible and safe following angioplasty of failing AV dialysis grafts. Limited data suggest a beneficial effect on restenosis. Longer term follow-up is needed to determine whether this will be clinically significant in maintaining graft patency. A successor trial is being mounted to evaluate the effect of radiation following angioplasty of clotted grafts. 50 oral A new method for the fast treatment therapy planning with IVUS imaging in intravascular brachytherapy

R. Novario 1. C. Bianchi 7, C. Sampietro I, F. Tanzi ~, L. Conte2, R. Lorusso I, M. VescovP, M. Caccia 4, M. Aleml4, C. Cappellim4 ~University Hospital, Medical Physics, Varese VA, Italy 2University of Insubria, Medical Physics, Varese VA, Italy ~Research System, Medical Physics, Agrate MI, Italy 4University of Insubria, Physics, Como CO, Italy The planned target volume in intracoronary brachytherapy is the vessel wall. The success of the treatment is based on the need of delivering doses possibly not lower than 8 and not higher than 30 Gy. An automatic procedure in order to acquire intravascular ultrasound images of the whole volume to be irradiated is pointed out; a motor driven pullback device, with velocity of the catheter of 0.5 and 1 mm/s allows to acquire the entire target volume of the vessel with a number of slices normally ranging from 400 to 1600. A semiautomatic segmentation and classification of the different structures in each slice of the vessel is proposed (fig. 1 ). The segmentation and the classification of the different structures (vessel walls, lumen, plaque, stent, etc.) allows the calculation of their volume; this is very useful in particular for plaque volume assessment in the follow-up of the patients. A 3D analyser tool was developed in order to visualize the walls, the lumen of the vessel, the stent and the plaque (fig. 2). The knowledge, for each axial slice, of the position of the source (in the centre of the catheter) and the position of the target (vessel