Endovascular brachytherapy using liquid Beta-emitting rhenium-188 for the treatment of long-segment femoropopliteal in-stent stenosis.

PURPOSE: To evaluate the efficacy and safety of endovascular brachytherapy with liquid beta-emitting rhenium-188 (Re-188) in patients with long-segment in-stent stenosis in the femoropopliteal segment. METHODS: From July 2009 to April 2011, 90 consecutive patients (59 men; mean age 68.3±10.3 years, range 43-86) with symptomatic in-stent stenosis/occlusion (24.6-cm mean lesion length) of the femoropopliteal segment underwent angioplasty and subsequent endovascular brachytherapy. The liquid beta-emitting Re-188 was applied to the target lesion within an angioplasty balloon using a dose of 13 Gy at a depth of 2 mm into the vessel wall. Clinical and angiographic follow-up data were collected up to 2 years. The main study endpoints were the 6- and 12-month primary patency rates defined as <50% in-stent stenosis as detected by duplex ultrasound. Clinical endpoints were the cumulative rates of death, amputation, and bypass surgery, as well as improvement in the Rutherford category and the ankle-brachial index. Results were correlated with patient and lesion characteristics. RESULTS: Primary technical success was achieved in all patients, with 1 early stent thrombosis, but no other complications related to the irradiation. Eighty-eight patients reached the 6-month and 82 the 12-month examinations; the primary patency was 95.2% and 79.8%, respectively. In-stent stenosis occurred in 9 patients, while 10 patients had reocclusion of the treated segment. During follow-up, there were 2 late acute thrombotic occlusions, both after discontinuation of clopidogrel. The clinical status improved in 67.0% and 62.2% of the patients after 6 and 12 months, respectively. No patient, lesion, or procedure variables were predictive of restenosis after EVBT. CONCLUSION: EVBT with liquid beta-emitting Re-188 was safe and effective in preventing restenosis in long-segment femoropopliteal ISS.

[Endovascular brachytherapy (EVBT) with Rhenium-188 for restenosis prophylaxis after angioplasty of infrainguinal lesions: early experience]. / Endovaskuläre Brachytherapie (EVBT) mit Rhenium-188 zur Restenoseprophylaxe nach Angioplastie infrainguinaler Läsionen: Erste Erfahrungen.

PURPOSE: Restenosis remains a major problem in percutaneous transluminal angioplasty (PTA) of peripheral arteries. The aim of this feasibility study was to evaluate the technical feasibility and safety of a new endovascular brachytherapy (EVBT) device with Rhenium-188 in restenosis prophylaxis of infrainguinal arteries. MATERIALS AND METHODS: From March 2006 to April 2009, 52 patients with 71 infrainguinal arterial lesions were treated with Re-188 to prevent restenosis after PTA. 40 patients with 53 lesions (24 de-novo lesions and 29 restenoses) were reexamined (clinic, color-coded duplex ultrasound) after a mean follow-up period of 12.7 months (2.6 to 25.1 months). The liquid beta-emitter Re-188 was introduced to the target lesion via an EVBT certified PTA balloon and a tungsten applicator. After the calculated irradiation time, Re-188 was aspirated back into the tungsten applicator. A dose of 13 Gy was applied at a depth of 2 mm into the vessel wall. RESULTS: After a mean follow-up of 12.7 months, the overall restenosis rate after Re-PTA was 15.1 % (8 / 53 lesions). The restenosis rate for de-novo lesions was 20.8 % (5 / 24) and 10.3 % for restenoses (3 / 29). In 4 patients reintervention was necessary (3 PTAs and 2 major amputations). No periprocedural complications were observed. No elevated radiation dose for the patient or the interventionalist was measured. CONCLUSION: EVBT with a Re-188 filled balloon catheter was technically feasible and safe after PTA of infrainguinal arterial lesions with restenosis rates lower than expected compared to published results. Treatment of restenoses seems to be more effective than de-novo lesions.

Endovascular brachytherapy with (192)Ir and (188)Re to treat de novo and recurrent infrainguinal restenoses.

We present a review of the literature on endovascular brachytherapy (EVBT) after percutaneous transluminal angioplasty (PTA) in the femoropopliteal and tibial arteries. The pathophysiological changes induced by PTA and EVBT within the vessel wall, technical considerations regarding 192Ir and 188Re, the results of clinical trials, and the medication required before, during, and after EVBT are summarized.

[Intravascular brachytherapy for peripheral arterial occlusive disease: systematic review of medical efficacy and health economic modelling]. / Intravaskuläre Brachytherapie bei peripherer arterieller Verschlusskrankheit: Systematische Ubersicht zur medizinischen Wirksamkeit und gesundheitsökonomische Modellierung.

CONTEXT: Percutaneous transluminal angioplasties (PTA) using balloon dilatation with or without stenting are performed to treat peripheral arterial occlusive disease (PAOD). Intravascular brachytherapy (IB) after PTA promises to reduce the restenosis rates. The present article addresses questions concerning medical efficacy and cost-effectiveness of IB in PAOD patients. METHODS: A systematic literature search for randomized controlled studies evaluating IB in PAOD was conducted in August 2007. Information synthesis was conducted using meta-analysis. Health economic modelling was performed on the basis of clinical assumptions derived from the meta-analysis and economical assumptions derived from the German Diagnosis Related Groups (G-DRG) 2007. RESULTS: Twelve publications covering seven studies about IB vs. no IB were included in the evaluation. IB after successful balloon dilatation showed a significant reduction in the rate of restenosis at six and/or twelve months (relative risk 0.62; 95% confidence interval: 0.46 to 0.84) and a significant delay in the time to recurrence of restenosis (17.5 vs. 7.4 months, p < 0.01). IB after stenting did not lead to significant results regarding the restenosis rates, but was more often associated with early and late occlusive thromboses. The incremental cost-effectiveness ratio per restenosis avoided for IB vs. no IB after successful balloon dilatation was--depending on the G-DRG used-Euro 8,484 and Euro 9,058, respectively. In the comparison of IB vs. no IB after stenting IB was demonstrated to be inferior to no IB. CONCLUSIONS: IB after successful balloon dilatation in PAOD can be recommended from a medical point of view. From the health economic perspective the answer is not yet clear. IB after stenting in PAOD cannot be recommended.

Endovascular brachytherapy in the femoropopliteal segment using 192Ir and 188Re.

This report presents a review of the literature on endovascular brachytherapy (EVBT) after percutaneous transluminal angioplasty (PTA) in the femoropopliteal segment. We summarize the pathophysiological changes induced by PTA and EVBT within the vessel wall, technical considerations regarding various radiation sources and their application, the impact of stents on the radial dose profile, recommendations for dosimetry of beta and gamma sources, results of experimental and clinical trials, and the medication required before, during, and after EVBT. We aim to help to identify patients who are eligible for EVBT, to choose an appropriate technical approach, and to initiate adequate antiplatelet and anticoagulant therapy.

A Phase II study of external-beam radiotherapy and endovascular brachytherapy with PTA and stenting for femoropopliteal artery restenosis.

PURPOSE: To assess the safety and seek evidence of efficacy of combined external-beam radiotherapy (EBRT) and endovascular brachytherapy in the treatment of stenotic vascular lesions. METHODS AND MATERIALS: Seventeen patients with high risk for restenosis of femoropopliteal arteries were enrolled in this study from February 2000 to August 2002. The external beam radiotherapy regimen consisted of 10 Gy in 5 fractions of 2 Gy, starting on Day 0. This was followed on Day 6 by angiography, stent placement, and intraluminal brachytherapy to a dose of 10 Gy at 1.2 mm from stent surface. The EBRT was continued from the same day to another 10 Gy in 2 Gy daily fractions for 5 days. RESULTS: The follow up ranged from 33 months to 60 months. At the time of analysis 15 of 17 patients were alive with patent stents. Of these, 10 were symptom-free. Two patients died of unrelated causes. CONCLUSIONS: The combination of EBRT and endovascular brachytherapy provided adequate dose distribution without any geographical miss or "candy wrapper" restenosis. No incidence of aneurysmal dilation of radiated vascular segment was observed. The treatment was feasible, well tolerated, and achieved 88% stenosis free survival.

Endovascular gamma irradiation for the prevention restenosis after angioplasty of femoropopliteal de novo stenoses.

The purpose of this study was to investigate the effectiveness and detect side effects of centered, overlapped endovascular gamma irradiation after angioplasty of de novo femoropopliteal stenoses. Thirty patients (age 65.3+/-9.2 years) with arterial occlusive disease were prospectively enrolled to receive endovascular gamma irradiation (192-iridium, 14 Gy centered at 2 mm vessel wall) immediately after percutaneous transluminal angioplasty (PTA) of femoropopliteal stenoses. Irradiation overlapped dilatation by 1-2 cm at each end. Follow-up involved angiography after 12 months; duplex sonography; and interviews before and after PTA and at 1, 6, and 12 months follow-up. PTA and centered endovascular irradiation were performed successfully in all patients. Three thromboembolic complications occurred during irradiation. Angiographic and clinical follow-up was possible in 28 patients. The angiographic degree of stenosis was 73.8%+/-16.3% before and 3.6%+/-23.5% after PTA and was 3.5%+/-43.7% at the 1-year follow-up. Restenosis (>50%) of the target lesion developed in three patients (10.7%) and edge stenoses (>30%) in nine patients (32.1%). An aneurysm of the irradiated segment in one patient was treated by stenting. The rate of retreatment was 17.9%. The vessel diameter after endovascular gamma irradiation and PTA of femoropopliteal stenoses remained stable. Restenosis, induction of edge stenoses, and aneurysm were reasons for reinterventions.

Endovascular brachytherapy after femoropopliteal balloon angioplasty fails to show robust clinical benefit over time.

PURPOSE: To determine if the short-term efficacy of adjunctive endovascular brachytherapy (EVBT) is maintained over time in patients undergoing balloon angioplasty (BA) of femoropopliteal atherosclerotic lesions. METHODS: To evaluate the long-term clinical and angiographic outcome of EVBT, 147 consecutive patients (82 men; mean age 70.8+/-8.5 years) with 147 treated limbs were randomized to BA with (n=72, 49%) or without (n=75, 51%) adjunctive EVBT (12 or 14-Gy from an (192)Ir source, no centering, a 5-mm reference depth). Sixty-eight (46%) limbs were treated for de novo and 79 (54%) for recurrent femoropopliteal lesions. Clinical follow-up at 1, 3, 6, and 12 months and annually thereafter included evaluation of symptoms, ankle-brachial index (ABI), and intra-arterial angiography for new/worsening symptoms or at follow-up between 2 and 5 years. Sustained clinical success was defined as improvement in ABI >or=0.1 and/or of symptoms without repeated target lesion revascularization. Angiographic restenosis was defined as >or=50% diameter reduction. Subgroup analysis was performed for de novo versus recurrent lesions. RESULTS: Mean clinical follow-up was 32.3+/-21.5 months. Angiographic follow-up was available in 83 (56%) patients (41 BA and 42 BA+EVBT) at a mean 31.8+/-20.7 months. Cumulative sustained clinical success rates at 1, 2, and 3 years, respectively, were 84.3%, 82.1%, and 76.4% after BA versus 82.4%, 69.8%, and 67.5% after BA+EVBT (p=0.26 by log-rank). Although the proportion of patients undergoing follow-up angiography was moderate, the freedom from angiographic restenosis at 1, 2, and 3 years was 70.7%, 63.1%, and 47.1% after BA versus 82.7%, 64.3%, and 64.3% after BA+EVBT (p=0.16 by log-rank). No differences were found between BA and BA+EVBT outcomes in patients with de novo versus recurrent femoropopliteal lesions. CONCLUSION: The seemingly beneficial short-term effects of BA+EVBT are not sustained in the longer term, with no robust clinical improvement after angioplasty of atherosclerotic de novo or recurrent femoropopliteal lesions at up to 5 years.

Endovascular brachytherapy for the prevention of restenosis after femoropopliteal angioplasty. Results of the VARA Trial.

AIM: Endovascular brachytherapy (EBT) has been proposed as a method to prevent restenosis. We performed a prospective randomised multicenter study to determine its efficacy for prophylaxis of restenosis after femoropopliteal percutaneous transluminal angioplasty (PTA). METHODS: Patients with symptomatic stenotic or totally occluding lesions in the femoropopliteal artery were randomised to be treated with PTA plus EBT or PTA alone. In case of EBT, 14 Gy was applied by an 192Ir source to the vessel wall. Clinical examination, ankle-brachial pressure index (ABPI) and duplex ultrasound were planned after 6 and 12 months. The primary endpoint was significant restenosis of the treated segment at duplex ultrasound after 12 months. RESULTS: Fifty-three of the 60 patients who eventually met the inclusion criteria could be studied. After 12 months, restenosis rates were 44% (12/27) in the PTA group versus 35% (8/23) in the PTA + EBT group (c2 test, P=0.51). There was no difference in mandatory reintervention between the 2 groups. Overall, EBT resulted in an absolute risk reduction of significant restenosis of 9%, yet in patients with totally occlusive disease this reduction was 32%. CONCLUSIONS: This study suggests an effect of EBT on the occurrence of restenosis only after PTA of occluded femoropopliteal lesions. Due to a too small number of patients analysed this difference is not statistically significant.

Endovascular brachytherapy: restenosis in de novo versus recurrent lesions of femoropopliteal artery--the Vienna experience.

PURPOSE: To determine the effectiveness of endovascular brachytherapy in the prevention of restenosis in recurrent versus de novo femoropopliteal lesions. MATERIALS AND METHODS: Ethics committee approval and patient informed consent were obtained. After they had undergone femoropopliteal angioplasty, 199 patients (mean age, 71.9 years +/- 9.6; 115 men, 84 women) were treated with either percutaneous transluminal angioplasty (PTA) and brachytherapy (n = 100) or PTA alone (n = 99). The patients were part of prospective randomized trials, the Vienna 2 and 3 trials, and were evaluated according to the stratification criterion of de novo or recurrent disease. Sixty-six of 134 patients with a de novo lesion and 34 of 65 patients with a recurrent lesion were randomly assigned to the PTA and brachytherapy arm; the remaining patients were treated with PTA alone. Outcomes were compared between the groups. The Student t test or one-way analysis of variance was used to compare continuous variables, and the chi2 test or Fisher exact test was used to assess dichotomous variables. Kaplan-Meier curves were calculated, and the log-rank test was performed to determine freedom from recurrence at 12 months in both groups. A multivariate Cox proportional hazard regression analysis was performed to evaluate the multivariate predictors of recurrence at 12-month follow-up. RESULTS: For patients with de novo lesions, the frequency of recurrence at 12 months was not significantly different between those who underwent brachytherapy and PTA and those who underwent PTA alone (24 [36%] of 66 patients vs 30 [44%] of 68 patients, P = .32). For patients with recurrent lesions, however, the 12-month recurrence rate was significantly lower in those who received brachytherapy than in those who did not (nine [26%] of 34 patients vs 22 [71%] of 31 patients, P = .004). CONCLUSION: Endovascular brachytherapy with gamma radiation significantly reduces the restenosis rate after femoropopliteal angioplasty of recurrent but not de novo lesions.

Optimal therapeutic approaches to femoropopliteal artery intervention.

Superficial femoral artery disease presents a complex challenge for therapy. The extent of vascular involvement may vary from focal disease with symptoms of intermittent claudication to long total occlusions manifest as critical limb ischemia. Optimal therapy requires understanding the available options including exercise programs, pharmacologic medical therapy, surgery and interventional endovascular therapy. Rapidly advancing endovascular technology for enabling safe intervention in complex, long occlusive segments of the superficial femoral artery continues to emerge. New devices like the SafeCross wire, Excimer laser, Silverhawk Atherectomy catheter, Cryoplasty catheter and new generations of bare metal and drug-eluting nitinol stents are shifting the paradigm for therapy from surgical to more endovascular treatment even for the most complex disease presentation.

De novo femoropopliteal stenoses: endovascular gamma irradiation following angioplasty--angiographic and clinical follow-up in a prospective randomized controlled trial.

PURPOSE: To assess and report the follow-up results of a randomized controlled trial on centered endovascular gamma irradiation performed after percutaneous transluminal angioplasty (PTA) for de novo femoropopliteal stenoses. MATERIALS AND METHODS: Thirty patients who underwent PTA for de novo femoropopliteal stenoses were randomly assigned to undergo 14-Gy centered endovascular irradiation (irradiation group, n = 15) or no irradiation (control group, n = 15). Intraarterial angiography was performed 6, 12, and 24 months after treatment; duplex ultrasonography (US), the day before and after PTA and 1, 3, 6, 9, 12, 18, and 24 months later. Treadmill tests and interviews were performed the day before PTA and 1, 3, 6, 9, 12, 18, and 24 months later. Results of angiography, duplex US, treadmill tests, and interviews were evaluated with the nonpaired t or the Fisher exact test. RESULTS: Baseline characteristics did not differ significantly between the two groups. Mean absolute individual changes in degree of stenosis, compared with the degrees of stenosis shortly after PTA, in the irradiation group versus in the control group were -10.6% +/- 22.3 versus 39.6% +/- 24.6 (P <.001) at 6 months, -2.0% +/- 34.2 versus 40.6% +/- 32.6 (P =.002) at 12 months, and 7.4% +/- 43.2 versus 37.7% +/- 34.5 (P =.043) at 24 months. The rates of target lesion restenosis at 6 (P =.006) and 12 (P =.042) months were significantly lower in the irradiation group. The numbers of target lesion re-treatments were similar between the groups, but target vessel re-treatments were more frequent in the irradiation group. There were no significant differences in interview or treadmill test results between the two groups at t test analysis. CONCLUSION: The degree of stenosis was significantly reduced 6, 12, and 24 months after angioplasty of de novo femoropopliteal stenoses in the patients who underwent endovascular irradiation.

Endovascular brachytherapy: effect on acute inflammatory response after percutaneous femoropopliteal arterial interventions.

PURPOSE: To investigate whether endovascular brachytherapy diminishes vascular inflammation in response to femoropopliteal percutaneous transluminal angioplasty (PTA) or stent implantation in two double-blind randomized-controlled trials. MATERIALS AND METHODS: Forty-seven consecutive patients from two double-blind randomized-controlled trials were studied. Patients either underwent femoropopliteal PTA with endovascular gamma irradiation (n = 8) or placebo irradiation (n = 7) or underwent PTA and stent implantation with brachytherapy (n = 15) or placebo irradiation (n = 17). High-sensitivity C-reactive protein (CRP), serum amyloid A (SAA), and fibrinogen levels were measured at baseline and 8, 24, and 48 hours after the intervention. The change of acute phase parameters from baseline to 48 hours after intervention indicated the extent of the inflammatory response and was compared between patients undergoing brachytherapy and those undergoing placebo irradiation. Fisher exact test was used for comparison of categorical data, and nonparametric statistical methods were applied for analysis of continuous data (Mann-Whitney U tests for unpaired data and Friedman analysis for repetitive measurements). RESULTS: Median patient age was 70 years (interquartile range, 56-74 years); 33 (70%) patients were men and 14 (30%) were women. Clinical characteristics and baseline values of acute phase parameters were similar between groups. A statistically significant increase in CRP, SAA, and fibrinogen values was observed after PTA and stent implantation, both in the patients who underwent brachytherapy and in those who underwent placebo irradiation. Compared with placebo irradiation, however, brachytherapy did not significantly reduce any acute phase parameter from baseline to 8, 24, or 48 hours after the intervention (P >.05 for all comparisons). CONCLUSION: Endovascular brachytherapy did not diminish early vascular inflammation in response to PTA or stent implantation and even induced a trend toward an increased inflammatory response.

Endovascular gamma irradiation of the iliac arteries: 1-year results from a clinical safety and feasibility study.

PURPOSE: To estimate safety and feasibility of vascular brachytherapy in iliac arteries. METHODS: Fourteen patients (11 men; mean age 56.7+/-9.9 years, range 44-81) with occlusive disease in 15 iliac arteries (7 external, 8 common) were treated with balloon dilation followed by irradiation from an iridium 192 source (15 Gy at 3 mm from the inner surface of the artery wall) applied with a PARIS centering catheter and bilateral 10-mm margins. Patients receiving stents for suboptimal angioplasty were prescribed a 6-month course of antiplatelet treatment with ticlopidine. Angiography was routinely scheduled for 6 months after intervention. RESULTS: There were no complications of the angioplasty procedure or EVBT treatment; 7 patients received stents for dissection or residual stenosis. Mean follow-up was 12.4+/-6.0 months. At 6-month angiography, 1 (6.7%) restenosis in a common iliac artery stent was found. Another patient with a common iliac artery stent developed transient lower limb ischemia at 4 months, probably due to temporary suspension of antiplatelet treatment and distal disease. CONCLUSIONS: Brachytherapy in the iliac arteries appears to be feasible and safe; longer follow-up in more patients is needed to determine its clinical utility in the prevention of restenosis.

[Intravascular brachytherapy in the prevention of vascular restenosis]. / Intravaskulární brachyterapie v prevenci cévních restenóz.

Vascular restenoses currently represent a major problem in the treatment of vascular stenoses. One of new approaches in the prevention of restenoses is intravascular brachytherapy. Intravascular brachytherapy uses local irradiation of the stenotic vessel segment by ionizing radiation with the aim of prevention of restenosis. This is a new rapidly developing multidisciplinary approach based on collaboration of specialties of intervention radiology, intervention cardiology, angiology, nephrology and radiation oncology. This review examines current options of intravascular brachytherapy as well as results of clinical trials evaluating the efficacy of intravascular brachytherapy in the different anatomical regions. Intravascular brachytherapy may substantially reduce the rate of restenoses. However, intravascular brachytherapy should be currently used only in the setting of clinical trials. Optimal method of irradiation of the stenotic segment of the vessel is still to be defined.

The role of radiation therapy in the treatment of femoropopliteal occlusive disease.

With the success of brachytherapy in the coronary vessels as a guide, it has also shown promising initial results as an adjunct for the treatment and prevention of restenosis of femoropopliteal occlusive disease. With the rapid evolution of endovascular therapy, defining the role of brachytherapy will become even more important. The purpose of this review is to provide an overview of the role of brachytherapy in the treatment of restenosis following femoropopliteal endovascular intervention.

Beta radiation and inhibition of recanalization after coil embolization of canine arteries and experimental aneurysms: how should radiation be delivered?

BACKGROUND AND PURPOSE: Beta radiation prevents recanalization after coil embolization. We sought to determine the effects of varying coil caliber, length, activity of 32P per centimeter of coil or per volume, and spatial distribution of coils on recanalization. METHODS: We studied the angiographic evolution of 81 canine maxillary, cervical, and vertebral arteries implanted with a variety of nonradioactive (n=29 arteries) or radioactive (n=52) devices. We compared 1- or 2-caliber 0.015 or 0.010 coils ion-implanted or not with 3 different activity levels (0.05 to 0.08, 0.06 to 0.12, 0.18 to 0.32 microCi/cm) of 32P and totaling 4, 8, and 16 cm in length for the same arterial volume. We also compared inhibition of recanalization by beta radiation delivered by stents, after coil occlusion proximal to or within the stent, with that delivered by coils placed within nonradioactive stents. We finally studied the angiographic evolution of canine lateral wall carotid aneurysms treated with 1 or 2 stents of various activity levels positioned inside the parent artery across the neck. Animals were killed at 4 and 12 weeks for macroscopic photography and pathological examination. RESULTS: All arteries (29 of 29) occluded with nonradioactive devices were recanalized, while 49 of 52 arteries (94%) implanted with 32P devices were occluded at 4 weeks. All aneurysms treated with stents, radioactive or not, demonstrated residual filling of the sac or of channels leading to the aneurysms at follow-up angiography at 4 weeks. CONCLUSIONS: The recanalization process found in the canine arterial occlusion model is minimally affected by coil caliber, number, and length or packing density. Beta radiation reliably inhibits this process, but thrombosis is an essential condition for the efficacy of a radioactive coil strategy.

Endovascular brachytherapy in peripheral arteries.

Increasing knowledge about the pathophysiology of the process leading to restenosis has given the rationale to investigate the potential role of radiation in the prevention of restenosis. Compared to the rapidly increasing experience in the coronary circulation, there is until now only a limited number of studies concerning the use of brachytherapy (BT) in the peripheral circulation. The-Vienna 2-Trial was the first randomized study to demonstrate the efficacy of endovascular BT for prophylaxis of restenosis after femoropopliteal percutaneous transluminal angioplasty. The cumulative patency rates at 12 months of follow-up were 63.6% in the PTA + BT-group and 35.3% in the PTA-group (p < 0.005), and the significant improvement in patency was also maintained after two years. The results of two ongoing randomized, double-blinded multicenter trials (PARIS; Vienna 3) have to be awaited before definitive recommendations can be given. The rather high incidence of late thrombotic occlusion after long-segment femoropopliteal stenting and endovascular BT requires optimization of the antithrombotic regimen.