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Published online before print June 13, 2005, 10.1148/radiol.2361040084
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(Radiology 2005;236:338-342.)
© RSNA, 2005

Vascular and Interventional Radiology

Endovascular Brachytherapy: Restenosis in de Novo versus Recurrent Lesions of Femoropopliteal Artery—The Vienna Experience1

Roswitha M. Wolfram, MD, Alexandra C. Budinsky, MS, Boris Pokrajac, MD, Richard Potter, MD and Erich Minar, MD

1 From the Departments of Angiology (R.M.W., A.C.B., E.M.) and Radiation Therapy (B.P., R.P.), Medical University of Vienna, Waehringer Guertel 18, A-1090 Vienna, Austria. Received January 27, 2004; revision requested April 6; final revision received July 18; accepted August 25. Address correspondence to R.M.W. (e-mail: rmwolfram{at}hotmail.com).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
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 {chi}2 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.

© RSNA, 2005


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
The percutaneous treatment of restenotic lesions in the femoropopliteal arteries, especially in the setting of long lesions and poor vessel runoff, is challenging, with a recurrence rate of more than 65% (1) regardless of the technique used. Randomized studies have revealed that a significant reduction in the recurrence rate and need for target lesion revascularization occurs in patients with in-stent restenosis if intracoronary radiation therapy with both gamma and beta emitters is used (2–5). Clinical data from investigations in the femoropopliteal artery showed a similar benefit, but most of those investigations (6) were conducted in inhomogeneous patient cohorts with longer de novo and restenotic lesions. Other trials investigating the effect of iridium 192 (192Ir) on de novo, predominantly short lesions yielded controversial results (2,7). Zehnder et al (8) reported positive results with endovascular brachytherapy in a study involving only restenotic lesions. To our knowledge, however, the effectiveness of brachytherapy in the prevention of recurrent stenosis in de novo lesions has not yet been compared directly with its effectiveness in recurrent lesions.

Restenotic lesions differ from de novo lesions in terms of morphologic characteristics and constituents (9,10); consequently, the response of restenotic lesions to radiation therapy might be different. Thus, the purpose of our study was to determine the effectiveness of brachytherapy in the prevention of restenosis in recurrent versus de novo femoropopliteal lesions.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 References
 
We analyzed records of 199 patients (mean age, 71.9 years ± 9.6; 115 men, 84 women) who had previously been randomly assigned to brachytherapy trials at the Vienna General Hospital in Vienna, Austria (the Vienna 2 trial [November 1996 to August 1998, 107 patients] and the Vienna 3 trial [October 1998 to July 2001, 92 patients]) (6,11) and who had completed 12-month clinical follow-up. Of these patients, 100 (53 from the Vienna 2 trial and 47 from the Vienna 3 trial; 66 patients with de novo and 34 with recurrent femoropopliteal lesions) were assigned to undergo PTA and brachytherapy. The 12-month outcomes were compared with those of 99 patients (54 from the Vienna 2 trial and 45 from the Vienna 3 trial; 68 patients with de novo and 31 with recurrent femoropopliteal lesions) who were treated with conventional PTA alone.

The following clinical characteristics were analyzed at baseline: sex; age; history of smoking; presence of arterial hypertension, diabetes, and hyperlipidemia; clinical stage (according to the Rutherford criteria [12]); and medication at the time of treatment (a calcium antagonist, angiotensin-converting enzyme inhibitor, statin, and/or fibrat). These data were independently evaluated by three investigators (R.M.W., A.C.B., and E.M.), and a consensus was reached in all cases. The angiographic characteristics evaluated at baseline were as follows: type of lesion (de novo or recurrent), presence of stenosis or occlusion, lesion length, treated length, active source length, presence of calcified lesions, and number of runoff vessels.

At 12-month follow-up, the following angiographic characteristics were evaluated: early occlusion, recurrence, presence of stenosis (binary restenosis was defined as narrowing of the initially treated segment by more than 50%) or occlusion, and target lesion revascularization. Lesion characteristics at follow-up were analyzed with either angiography or duplex ultrasonography (US). All data were independently evaluated by four investigators (R.M.W., B.P., A.C.B., and E.M.), and a consensus was reached in all cases. All investigators involved in the follow-up examinations were blinded to treatment group. Angiographic success, periprocedural complications and in-hospital adverse events, and radiation-related complications were assessed in all patients (R.M.W., B.P., E.M.).

Brachytherapy procedures with the gamma emitter 192Ir were performed by using a remote afterloading device (microSelectron; Nucletron, Veenendaal, the Netherlands). Study protocols, revascularization techniques, and brachtherapy procedures have been described previously (6,11). Briefly, for the Vienna 2 trial, a dose of 12 Gy was administered without a centering device 3 mm from the source axis; for the Vienna 3 trial, a dose of 18 Gy was administered by using a centering device at a depth calculated by subtracting the radius from the reference depth and adding 2 mm. Inclusion and exclusion criteria were similar for the two trials. Among the requested inclusion criteria for both trials was a de novo lesion longer than 5 cm or a recurrent lesion of any length (6,11). The mean lesion length in this study was longer than that in previous investigations (13). Each patient gave his or her written informed consent to participate in the study, which was approved by the hospital's ethics committee. This written informed consent included a separate paragraph for any further use of the originally obtained data, such as for this retrospective analysis.

All patients received aspirin (100 mg/d) before the procedure, and aspirin administration was continued indefinitely afterward.

Primary End Point
The primary end point of this study was binary restenosis, which was defined as more than 50% narrowing of the diameter of the initially treated segment, at 12-month follow-up. In the Vienna 2 trial, the primary end point was angiographic patency, which was defined as less than 50% restenosis of the target lesion, at 6 months and recurrence at 12 months as verified with duplex US. A focal increase in peak systolic velocity of at least 140% (corresponding to a peak velocity ratio of at least 2.4) was considered equivalent to a stenosis of more than 50% (14). In the Vienna 3 trial, the primary end point was angiographic patency at 12 months.

Statistical Analysis
The clinical and angiographic variables were compared between patients who underwent PTA alone and those who underwent both PTA and brachytherapy for both de novo and recurrent lesions. Continuous variables are reported as means ± standard deviations, and dichotomous variables are reported as percentages. The Student t test or one-way analysis of variance was used to compare continuous variables, and the {chi}2 test or Fisher exact test was used to assess dichotomous variables. A P value of less than .05 was considered to indicate a statistically significant difference.

Kaplan-Meier curves were calculated, and the log-rank test was performed to determine freedom from recurrence at 12 months. The time of recurrence was judged by recurrence of symptoms. In clinically asymptomatic patients, the date of the scheduled follow-up visit (3, 6, or 12 months) was used as the date of recurrence. Data for patients who died or were lost to follow-up without recurrence were censored from the date of the last follow-up examination.

Univariate and multivariate Cox proportional hazard regression analyses were performed to evaluate the univariate or multivariate predictors of recurrence at 12-month follow-up. The variables used in these analyses included brachytherapy, sex, clinical stage, hypertension, history of diabetes or smoking, hypercholesterolemia, lesion length, and whether the lesion was de novo or recurrent. Again, the time of recurrence was judged by recurrence of symptoms. In clinically asymptomatic patients, the date of the scheduled follow-up visit (3, 6, or 12 months) was used as the date of recurrence. Data for patients who died or were lost to follow-up without recurrence were censored from the date of their last follow-up examination. A stepwise Cox regression model (including brachytherapy, treatment protocol of the trial [Vienna 2 or Vienna 3], sex, clinical stage, hypertension, history of diabetes or smoking, hypercholesterolemia, and whether the lesion was de novo or recurrent) was applied to reveal variable-to-variable interactions, variable-to-log (time) interactions, and nonlinearities of the variables (eg, lesion length). These variables were included in the original model if the P value was less than .01. Model assumptions were checked by using the log likelihood {chi}2 test. Independent variables were expressed as hazard ratios with 95% confidence intervals. All calculations were performed with SPSS for Windows version 11.5 (SPSS, Chicago, Ill).


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 References
 
Clinical data from patients at baseline are shown in Table 1. The patients represented a typical cohort with peripheral vascular disease and had a high prevalence of cardiovascular risk factors, which were, except for hyperlipidemia (de novo vs recurrent lesions, P < .05), equally distributed. Clinical and angiographic characteristics of all patients at baseline and 12-month follow-up data are given in Table 2. All patients had immediate angiographic success without complications. There were no procedural or in-hospital adverse events or radiation-related complications. Angiographic follow-up was performed in 148 patients (Table 2); in the remaining patients, recurrence was evaluated with duplex US, as described previously (14).


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  		TABLE 1. Patient Clinical Characteristics at Baseline

 

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  		TABLE 2. Angiographic Characteristics at Baseline and Angiographic or US Characteristics at 12-month Follow-up

 
For the patients with de novo lesions, recurrence was verified with angiography or duplex US in 24 of the 66 patients (36%) who underwent both PTA and brachytherapy and in 30 of the 68 patients (44%) treated with PTA alone; this indicates an 8% reduction in recurrence after PTA and brachytherapy compared with recurrence after PTA alone (P = .28, {chi}2 test) (Fig 1). For the group initially treated for restenotic lesions, however, the recurrence rate was significantly lower in patients treated with PTA and brachytherapy than in those treated with PTA alone (26% vs 71%, respectively; P < .001, {chi}2 test), with a 45% reduction of recurrence in the PTA and brachytherapy group (Fig 2). When we compared results in patients with restenotic lesions with those in patients with de novo lesions, patients with de novo lesions treated with PTA alone had a significantly better outcome than did those treated with PTA and brachytherapy (P = .005, log-rank test) (Fig 3), whereas the 12-month outcomes of patients treated with PTA and brachytherapy were similar between the two groups (P = .62, log-rank test) (Fig 4).



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  		Figure 1. Kaplan-Meier graph shows recurrence (restenosis) rates after femoropopliteal PTA in patients with de novo lesions according to treatment group. Numbers below x-axis are numbers of patients who underwent PTA alone (top row) or PTA and brachytherapy (BT) (bottom row) and were at risk for recurrence. For patients treated for de novo lesions, there was no difference in recurrence rate between the two treatment groups (P = .32, log-rank test).

 


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  		Figure 2. Kaplan-Meier graph shows recurrence (restenosis) rates after femoropopliteal PTA in patients with recurrent lesions according to treatment group. Numbers below x-axis are numbers of patients who underwent PTA alone (top row) or PTA and brachytherapy (BT) (bottom row) and were at risk for recurrence. The difference in recurrence rates between the two treatment groups was significant (P = .004, log-rank test).

 


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  		Figure 3. Kaplan-Meier graph shows recurrence (restenosis) rates for patients treated with PTA alone. Numbers below x-axis are numbers of patients with de novo (top row) or recurrent (bottom row) lesions who were at risk for recurrence. The difference in recurrence rates between the de novo and the recurrent lesions was significant (P = .005, log-rank test).

 


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  		Figure 4. Kaplan-Meier graph shows recurrence (restenosis) rates for patients treated with PTA and brachytherapy. Numbers below x-axis are numbers of patients with de novo (top row) or recurrent (bottom row) lesions who were at risk for recurrence. There was no significant difference in recurrence rates between the de novo and the recurrent lesions (P = .62, log-rank test).

 
After we performed a multivariate Cox proportional hazard regression analysis that included brachytherapy, sex, clinical stage, hypertension, diabetes, smoking, hypercholesterolemia, lesion length, and number of runoff vessels in patients treated for recurrent lesions as variables, we found that clinical stage 3 or 4 (hazard ratio, 0.37; 95% confidence interval, 0.17–0.82; P = .02) and treatment with brachytherapy (hazard ratio, 3.09; 95% confidence interval, 1.33–7.16; P = .009) remained independent predictors for repeat recurrence at 12 months. We could not detect independent predictors for recurrence at 12 months in patients with de novo lesions.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
References
 
The results of this retrospective analysis of the 12-month outcomes of patients who underwent PTA with brachytherapy for restenotic versus de novo lesions in the femoropopliteal artery confirm and extend earlier observations that brachytherapy is valuable in the treatment of restenotic lesions (15–17). In this study, we demonstrated that brachytherapy with 192Ir effectively reduced the rate of restenosis by 45% compared with the rate of restenosis after PTA alone, without adverse periprocedural events. However, confirming a speculation previously made in a report of trials in coronary and peripheral arteries (4), we found that brachytherapy does not improve patency in longer de novo lesions.

Restenotic lesions differ from de novo lesions in terms of their morphologic characteristics and constituents (9,10). De novo lesions consist mostly of plaques with a high content of lipid-loaded macrophages, as well as calcified, mostly acellular areas. Recurrence after previous PTA, however, is mainly due to neointimal hyperplasia as a response to plaque rupture and vessel wall injury during balloon angioplasty (18).

The postulated mechanisms for the effect of brachytherapy include, among others, cell cycle arrest and a consequent inhibition of cell migration and proliferation. This suggests that restenotic lesions are the optimal target for brachytherapy, as is further emphasized by results of clinical trials in the coronary arteries (4,16).

Thus far, only a limited number of investigations have addressed the effectiveness of brachytherapy in the femoropopliteal arteries, and, although the reported results were promising, several of these investigations involved a mixed population with both restenotic and de novo lesions (6,11). In a trial in which only de novo lesions were investigated, data were controversial (7). Therefore, there is still no proper answer as to which treatment modality is currently the best approach for each type of lesion.

This study was a retrospective analysis of prospectively collected data, and therefore our results and conclusions are subject to limitations inherent in all such studies. Angiographic follow-up was not available for all patients. Furthermore, two different radiation protocols were used.

In conclusion, the encouraging results of this study suggest that brachytherapy with the gamma emitter 192Ir is a valuable therapeutic option for patients with restenotic lesions in the femoropopliteal artery. Furthermore, we were able to demonstrate that, at least in the context of balloon angioplasty alone (without stent implantation), brachytherapy did not improve the frequency of recurrence in longer de novo lesions at 12 months in this high-risk patient cohort. For de novo lesions in peripheral arteries, drug-eluting stents show promise, as emphasized by recently published results from clinical coronary trials (16), and should be evaluated in future studies. In addition, the potential benefit of brachytherapy for de novo lesions should be evaluated for special patient subgroups, such as patients with diabetes.


   FOOTNOTES
 

Abbreviations: PTA = percutaneous transluminal angioplasty

Authors stated no financial relationship to disclose.

Author contributions: Guarantors of integrity of entire study, all authors; study concepts and design, R.M.W., B.P., E.M., R.P.; literature research, R.M.W., A.C.B.; clinical studies, R.M.W., E.M., B.P.; data acquisition and analysis/interpretation, R.M.W., A.C.B., E.M., B.P.; statistical analysis, R.M.W., A.C.B.; manuscript preparation, R.M.W.; manuscript definition of intellectual content, editing, revision/review, and final version approval, all authors


   References
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 

  1. Schillinger M, Mlekusch W, Haumer M, Sabeti S, Ahmadi R, Minar E. Angioplasty and elective stenting of de novo versus recurrent femoropopliteal lesions: 1-year follow-up. J Endovasc Ther 2003; 10:288–297.[CrossRef][Medline]
  2. Waksman R, Laird JR, Jurkovitz CT, et al. Intravascular radiation therapy after balloon angioplasty of narrowed femoropopliteal arteries to prevent restenosis: results of the PARIS feasibility clinical trial. J Vasc Interv Radiol 2001; 12:915–921.[Medline]
  3. Waksman R, Ajani AE, Pinnow E, et al. Twelve versus 6 months of clopidogrel to reduce major cardiac events in patients undergoing gamma-radiation therapy for in-stent restenosis: Washington Radiation for In-Stent Restenosis Trial (WRIST) 12 versus WRIST PLUS. Circulation 2002; 106:776–778.[Abstract/Free Full Text]
  4. Ajani AE, Waksman R. The WRIST series: what have we learnt? Herz 2002; 27:23–29.[CrossRef][Medline]
  5. Cha DH, Ajani AE, Cheneau E, Waksman R. Clinical trials of intracoronary gamma radiation therapy for in-stent restenosis. J Invasive Cardiol 2002; 14:432–437.[Medline]
  6. Minar E, Pokrajac B, Maca T, et al. Endovascular brachytherapy for prophylaxis of restenosis after femoropopliteal angioplasty: results of a prospective randomized study. Circulation 2000; 102:2694–2699.[Abstract/Free Full Text]
  7. Krueger K, Landwehr P, Bendel M, et al. Endovascular gamma irradiation of femoropopliteal de novo stenoses immediately after PTA: interim results of prospective randomized controlled trial. Radiology 2002; 224:519–528.[Abstract/Free Full Text]
  8. Zehnder T, von Briel C, Baumgartner I, et al. Endovascular brachytherapy after percutaneous transluminal angioplasty of recurrent femoropopliteal obstructions. J Endovasc Ther 2003; 10:304–311.[CrossRef][Medline]
  9. Mintz GS, Pichard AD, Kent KM, Satler LF, Popma JJ, Leon MB. Intravascular ultrasound comparison of restenotic and de novo coronary artery narrowings. Am J Cardiol 1994; 74:1278–1280.[CrossRef][Medline]
  10. Mehran R, Dangas G, Mintz GS, et al. Atherosclerotic plaque burden and CK-MB enzyme elevation after coronary interventions: intravascular ultrasound study of 2256 patients. Circulation 2000; 101:604–610.[Abstract/Free Full Text]
  11. Pokrajac B, Potter R, Wolfram RM, et al. Endovascular brachytherapy prevents restenosis after femoropopliteal angioplasty: results of the Vienna-3 randomised multicenter study. Radiother Oncol 2005; 74:3–9.[CrossRef][Medline]
  12. Rutherford RB, Becker GJ. Standards for evaluating and reporting the results of surgical and percutaneous therapy for peripheral arterial disease. Radiology 1991; 181:277–281.[Abstract/Free Full Text]
  13. Krueger K, Zaehringer M, Bendel M, et al. De novo femoropopliteal stenoses: endovascular gamma irradiation following angioplasty—angiographic and clinical follow-up in a prospective randomized controlled trial. Radiology 2004; 231:546–554.[Abstract/Free Full Text]
  14. Ranke C, Creutzig A, Alexander K. Duplex scanning of the peripheral arteries: correlation of the peak velocity ratio with angiographic diameter reduction. Ultrasound Med Biol 1992; 18:433–440.[CrossRef][Medline]
  15. Waksman R, Bhargava B, White RL, et al. Intracoronary radiation for patients with refractory in-stent restenosis: an analysis from the WRIST-Crossover Trial. Washington Radiation for In-stent Restenosis Trial. Cardiovasc Radiat Med 1999; 1:317–322.[CrossRef][Medline]
  16. Waksman R, White RL, Chan RC, et al. Intracoronary gamma-radiation therapy after angioplasty inhibits recurrence in patients with in-stent restenosis. Circulation 2000; 101:2165–2171.[Abstract/Free Full Text]
  17. Waksman R, Bhargava B, White L, et al. Intracoronary beta-radiation therapy inhibits recurrence of in-stent restenosis. Circulation 2000; 101:1895–1898.[Abstract/Free Full Text]
  18. Schwartz RS, Henry TD. Pathophysiology of coronary artery restenosis. Rev Cardiovasc Med 2002; 3(suppl 5):S4–S9.



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This Article
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