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Vascular and Interventional Radiology |
1 From the Depts of Radiology (K.K., M.Z., D.S., D.W., K.L.) and Radiooncology (M.B., M.N., R.P.M.), and the Institute for Med Statistics, Informatics and Epidemiology (H.S.), Univ of Cologne, Joseph-Stelzmann-Str, D-50924 Cologne, Germany. From the 2001 RSNA scientific assembly. Received Mar 19, 2003; revision requested May 7; final revision received Aug 6; accepted Sep 16. Supported by a grant from "Cologne Fortune," a research program of the Univ of Cologne, Nr. 1/98. Address correspondence to K.K. (e-mail: karsten.krueger@uni-koeln.de).
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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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.
© RSNA, 2004
Index terms: Arteries, radiation • Arteries, restenosis, 92.721 • Arteries, stenosis or obstruction, 92.721 • Arteries, transluminal angioplasty, 92.1281, 92.1282, 92.1286, 92.454 • Iridium, radioactive
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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The high rate of restenosis is a limitation of PTA in the treatment of femoropopliteal stenoses (8,9). In contrast to the plethora of studies on coronary arteries, there is a paucity of reports on randomized controlled trials performed to investigate the endoluminal irradiation of femoropopliteal arteries. Although initial data indicate that irradiation can prevent restenoses of femoropopliteal arteries (10–12), there is limited evidence of the effectiveness of brachytherapy in preventing restenoses after angioplasty of de novo femoropopliteal stenoses.
Furthermore, in most of the published studies on peripheral arteries, irradiation was performed without centering the radiation source in the vessel (10–12). There are still a number of questions to be elucidated: Does this treatment completely inhibit or only delay the development of restenosis? How frequently do acute and late complications occur following centered irradiation of femoropopliteal arteries?
In a prospective randomized controlled trial, centered endovascular irradiation with the gamma emitter iridium 192 (192Ir) was performed immediately after PTA of de novo femoropopliteal stenoses. The results of this previously published interim analysis (13) indicated that gamma irradiation led to a significant improvement in vessel diameter and a lower restenosis rate at 6-month follow-up. The purpose of our study was to assess and report the 12- and 24- month angiographic and clinical follow-up results of postangioplasty endovascular irradiation.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Patients
The details of the study were recently published (13). In brief, 30 consecutive patients aged 50 years or older with stage 2a–3 arterial occlusive disease (according to the classification system of Fontaine) and de novo femoropopliteal stenosis that had not been previously treated with any surgical procedure were enrolled in the study. The maximum length of the stenoses was 8 cm (length of occlusion <5 cm). Exclusion criteria were greater than 30% residual stenosis immediately after angioplasty, nontreated stenosis proximal to the site of angioplasty, less than one completely patent runoff vessel, and any malignant disease. The ages, sexes, and risk factors for vascular disease of the patients were documented. Balloon angioplasty was the only endovascular treatment allowed.
All patients received 100 mg of aspirin and a subcutaneous injection of a low dose (7,500 IU) of heparin (Hoffmann-La Roche, Grenzbach-Wyhlen, Germany) beginning 1 day before PTA. During the intervention, 5,000–7,500 IU of heparin was administered by means of intravenous bolus. Heparin therapy was continued for 24 hours, and aspirin (100 mg daily) was continued indefinitely. One patient received clopidogrel (Plavix; Sanofi-Synthelabo, Berlin, Germany) instead of aspirin.
The patients were randomly assigned to two groups: those who did (irradiation group) and those who did not (control group) undergo centered endovascular irradiation, which was performed after successful PTA and placement of a centering catheter. No patient was excluded from the study after this randomization.
Outcome Measures
The primary outcome measure was the individual absolute change in the angiographically defined degree of stenosis of the dilated vessel segment—that is, the target lesion—from baseline (ie, immediately following PTA) to a definite outcome period—specifically, at 12-month follow-up. We also evaluated and present the extended 24-month follow-up results. The results at 6-month follow-up are provided for comparison. Secondary outcome measures included the absolute degree of stenosis of the dilated vessel segment; the opacity of the contrast material in the stenosis at 12- and 24-month angiographic follow-up examinations; and the results of structured interviews, color duplex ultrasonography (US), and treadmill tests.
Interventional Procedures and Imaging
All interventional procedures and follow-up angiographic examinations were performed by using intraarterial digital subtraction angiography (Multistar T.O.P. unit; Siemens Medical Systems, Erlangen, Germany). Two authors (K.K., K.L.), either alone or together, performed balloon dilation according to conventional practice by using a crossover or antegrade approach. Optimal spatial resolution was verified with a 20-cm image intensifier before, during, and after PTA. The diameter of the balloon (Sailor PTA Catheter; Invatec, Concesio Brescia, Italy) depended on the diameter of the vessel proximal to the stenosis. The length of the PTA balloon was chosen according to the length of the stenosis. Dilation lasted exactly 1 minute. Additional 1-minute dilations were performed until the degree of residual stenosis was less than 30%.
The following parameters were documented: the length of the stenosis, the location of the PTA balloon during angioplasty, the length and diameter of the PTA balloon, and the duration of and pressure resulting from the PTA balloon inflation. The morphologic features of the stenoses were described as concentric or eccentric. After successful angioplasty, an angiogram of the treated leg was obtained. During the entire procedure, a ruler was fastened to the skin of the treated leg to measure the length of the stenosis and control the position of the centering catheter during irradiation.
The catheter for source centering (Paris; Guidant, Tememla, Calif) was inserted into the artery after successful angioplasty by the same radiologist who performed the balloon angioplasty (K.K. or K.L.), who had, respectively, 8.5 or 22.0 years of experience in interventional radiology. The length of the segmented balloon for source centering was always 10 cm, and it overlapped the dilated stenosis by at least 1 cm at each end. The diameter of the centering catheter was 1 mm smaller than the diameter of the PTA balloon catheter. Before the patient was transported to the brachytherapy unit, the exact position of the centering device in relation to the ruler was verified and documented with radiography and the sheath with the centering catheter was taped to the skin.
Endovascular Irradiation
Two authors (M.B. and M.N., with 10 and 22 years of experience in radiation therapy, respectively) together performed endovascular irradiation by using an 192Ir wire with a diameter of 0.9 mm (Nucletron [Micro] Selectron High Dose Rate Afterloader; Nucletron BV, Veenendaal, the Netherlands). The correct position of the centering catheter—that is, the position of the radiopaque marker at the top of the centering catheter in relation to the ruler—was verified by using radiography and documented before irradiation by the same radiologist who inserted the centering catheter. The radiation dose was 14 Gy delivered 2 mm deep to the vessel wall. The entire length of the centering catheter was irradiated. The centering balloon catheter was inflated to a pressure of 4 atm during irradiation. The irradiation time varied between 207.2 and 453.7 seconds (mean, 320.44 seconds ± 94.11 [SD]). The minimum current source strength was 4.174 Ci (15.44 x 1010 Bq), and the maximum current source strength was 9.101 Ci (33.67 x 1010 Bq) (mean, 6.52 Ci [24.12 x 1010 Bq] ± 1.96). After 3 minutes, the irradiation was interrupted for 120 seconds and the centering balloons were deflated.
The control patients underwent the same procedure that the patients in the irradiation group underwent, with the exception that an inactive dummy probe rather than a gamma source probe was inserted. In the control group, the centering catheter was inflated at the same time that irradiation would have been performed.
The centering catheter was removed immediately after irradiation, and the patients were transported back to the catheter unit, where an angiogram was obtained to see if any acute complications such as thromboembolic occlusion of a peripheral vessel or dissection and acute occlusion within the irradiated region had occurred during or as a result of the procedure.
Data Evaluation
To determine an angiographic score, we rated all angiograms according to a system that was proposed by the Society for Vascular Surgery and modified by Williams et al (14). The details of the scoring system have been previously described (13). In brief, the arteries of the treated leg were divided into four segments: abdominal, pelvic, thigh, and calf segments. Each artery of the treated leg was assigned a vascular disease score of 0 if it was normal (had no stenosis) or the degree of stenosis was less than 20%, a score of 1 if the degree of stenosis was between 20% and 49%, or a score of 2 if the degree of stenoses was between 50% and 99%. If less than half the length of the artery was occluded, the vessel was assigned a score of 2.5. If more than half the length of the artery was occluded, the vessel was assigned a score of 3.
Each artery was also assigned a level of importance—for example, importance level 2 for the superficial femoral artery and importance level 3 for the common iliac artery. The resistance of each segment was calculated by multiplying the vessel importance level by the vascular disease score, and the total resistance was calculated by adding the resistance of the four segments. All angiograms were read by two authors (K.K., K.L.), and a consensus interpretation was reached in all cases.
The maximum degree of stenosis (ie, diameter reduction) and of opacity reduction during the passage of the contrast material before and after PTA and at follow-up was quantified (by M.Z.) by using vessel edge detection software (Siemens Medical Systems), as described previously (13).
Follow-up
By using a structured interview, authors (D.S., M.Z., D.W.) questioned the patients 1 day before and 1, 3, 6, 9, 12, 18, and 24 months after they were randomly assigned to one of the two groups. Color-coded duplex US examinations were performed (by M.Z., D.S., and D.W.) 1 day before and 1 day after the randomization and 1, 3, 6, 9, 12, 18, and 24 months after treatment. The patients underwent treadmill tests (performed by M.Z., D.S., D.W.) the day before and 1, 3, 6, 9, 12, 18, and 24 months after PTA. Each interview, color-coded duplex US examination, and treadmill test was performed by one of the cited investigators. Intraarterial angiography was performed (by M.Z.) 6, 12, and 24 months after angioplasty.
Details of the structured interview are given in the previously published report (13). In brief, the patients were asked to give their maximum walking distance capability and the degree of their leg pain during a low-, normal-, and high-velocity walking distance of 100 m and when climbing one to three stair steps. All answers were scored, and the maximum score was 35 points.
The treadmill test was performed according to the recommendations of Rutherford et al, with the patient walking on the treadmill at a pace of 3 km per hour and on a slope of 12° for not more than 10 minutes (15). For the patients with known heart disease, the slope was reduced to 6° or 0°. For each patient, the slope at all follow-up examinations was kept constant. The initial claudication distance (ie, walking distance capability with initial symptoms) and the termination of the test (ie, how long the test was performed, in meters) were documented.
The thigh-brachial index of the proximal and distal parts of the thigh and the ankle-brachial index of the distal part of the calf of the treated leg were measured by using color duplex US. In addition, the peak velocity ratio of the stenosis (ratio of maximum blood velocity before the stenosis to maximum blood velocity within the stenosis) was determined.
Follow-up angiograms of the treated leg were obtained with intraarterial digital subtraction angiography. We took efforts to image the former balloon dilation site in the same projection used to image the region of angioplasty. The vessel diameter and the contrast material opacity within the former stenotic region (ie, target lesion) were measured, as described earlier (by M.Z.). Restenosis of the target lesion was defined as a diameter reduction of more than 50% within the former stenotic region. A new stenotic lesion of more than 30% diameter reduction at the proximal or distal end of the treated segment was defined as an edge stenosis. Edge stenoses were documented. New stenoses inside and outside of the irradiated part of the vessel—that is, not including the former stenotic region—also were documented. The target vessel was the femoropopliteal artery. All re-treatments of target lesions and target vessels of the treated legs were documented.
All investigators involved in the follow-up examinations (M.Z., D.S., D.W.) were blinded in terms of which groups the patients were randomly assigned to. The group randomizations were known only to the investigators who performed angioplasty or endovascular irradiation (K.K., K.L., MB, M.N.). Patients were blinded as to whether they had received an inactive dummy probe or a gamma source probe.
Rationales and Methods for Statistical Analysis
A nonpaired t test was used to test the hypothesis of equal means of the primary target variable—that is, the individual change in angiographically defined degree of stenosis—in both groups after 6, 12, and 24 months. The secondary clinical parameters—specifically, the absolute degree of stenosis; the contrast material opacity in the stenosis; and the structured interview, color-coded duplex US, and treadmill test results—were analyzed in a statistically nonconformant sense (ie, exploratively). Depending on the respective scale dignity, nonparametric respectively parametric tests were used to describe differences. All P values were reported without adjustment for multiplicity and/or interim monitoring. The P values yielded from the t tests were two sided (ie, with the null hypothesis being equality of means).
To perform an intention-to-treat analysis, we imputed missing values for the primary target variable by using individual linear interpolation if a value before and after the missed value was available. In dropout cases (ie, following values that were not available), the missed values were imputed by using the mean of the nonmissing values of the other group (16). Computations for the test statistics were performed by using a computer program (SPSS 11 for Windows; SPSS, Chicago, Ill). The summary statistics cited in the text usually are mean values ± SDs.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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2 cm) stenoses were treated. Endovascular brachytherapy or placement of a dummy probe was performed successfully in all patients. During angioplasty and brachytherapy, one patient developed a thromboembolic occlusion of a lower limb vessel that required local thrombolysis with 100,000 IU of urokinase per hour.
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The mean proximal thigh-brachial indexes for the irradiation and control groups before PTA were 1.13 ± 0.14 and 1.06 ± 0.18, respectively (P = .20, t test). The day after angioplasty, these values changed to 1.14 ± 0.18 and 1.05 ± 0.14, respectively (P = .15, t test). The mean distal thigh-brachial indexes for the irradiation and control groups before PTA were 0.87 ± 0.22 and 0.78 ± 0.22, respectively (P = .24, t test). The day after angioplasty, these values increased to 1.10 ± 0.13 and 1.08 ± 0.11, respectively (P = .61, t test).
Treadmill tests.—The mean pain-free walking distance capabilities for the irradiation and control groups before PTA were 92.2 m ± 113.1 and 95.9 m ± 123.2, respectively (P = .83, t test). One month after PTA, these values increased to 308.5 m ± 191.2 and 288.1 m ± 193.9, respectively (P = .68, t test). The mean total walking distance capabilities (ie, with and without pain) for the irradiation and control groups before PTA were 206.2 m ± 150.1 and 190.2 m ± 166.6, respectively (P = .78, t test). One month after PTA, these values increased to 344.5 m ± 171.7 and 321.1 m ± 176.0, respectively (P = .72, t test).
Interviews.—The mean walking distance–leg pain scores at interviews with the irradiation and control groups conducted before PTA were 16.3 ± 6.8 and 13.9 ± 8.4, respectively (P = .39, t test). One month after PTA, these scores improved to 28.4 ± 4.5 and 25.7 ± 5.9, respectively (P = .18, t test).
Follow-up Results
An overview of the rates of complete and incomplete follow-up examinations is provided in Table 4. One patient in the control group refused to undergo 12- and 24-month angiographic follow-up examinations. One patient in the irradiation group died because of gastric bleeding 15 months after randomization.
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After 6 months, recurrent stenosis of greater than 50% was observed in seven patients in the control group (restenosis rate, 47%) but in none of the patients in the irradiation group (P = .006). Twelve months after angioplasty, the restenosis rate was 33% (five of 15 patients) in the control group and 0% in the irradiation group (P = .042).
According to intention-to-treat analysis results, during the observation period of 24 months, the difference between the two groups in terms of the angiographically defined restenosis rate became smaller: Five patients in the control group and two in the irradiation group had greater than 50% stenosis at 24 months (P = .39). Of the two patients who underwent irradiation and had greater than 50% stenosis, one developed an occlusion of the PTA region secondary to restenosis. The other patient had a proximal occlusion in the superficial femoral artery—probably a complication of the puncture for PTA—that persisted farther downstream and included the target lesion. At the 6- and 12-month angiographic follow-up examinations, the target lesion was completely normal in this patient.
At 24-month follow-up, the rate of target lesion re-treatment (including interventional and surgical procedures for revascularization of the target lesion) was similar between the two groups (Table 5). One patient in the irradiation group underwent repeat dilation because of a restenosis of the target lesion 24 months after randomization. Two patients in the control group were re-treated: one patient who underwent femoropopliteal bypass surgery because of superficial femoral artery occlusion secondary to target lesion restenosis 13 months after PTA and one patient who was treated with repeat PTA for restenosis after 24 months.
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Follow-up angiography performed at 12 and 24 months revealed a higher but not significant rate of edge stenoses (ie, new stenoses of more than 30%) in the irradiation group (Table 6). In two patients in the irradiation group, these lesions were symptomatic (walking distance capability < 200 m) and required angioplasty. The occurrence of new stenotic lesions outside of the vessel segment was slightly higher in the irradiation group (Table 6).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Two patients in the irradiation group had markedly deteriorated 24-month follow-up results. One of these patients developed an occlusion of the target lesion secondary to a restenosis. The other patient had an occlusion of the proximal femoral artery—probably a complication of the antegrade puncture—that spread farther distally to the orifice of a collateral vessel of the deep femoral artery and included the target lesion. In the control group, restenoses occurred within the first 6 months after angioplasty. Thereafter, the mean vessel diameters of the target lesions remained stable or slightly decreased.
The rate of target lesion re-treatment was similar between the two groups: Target lesions in two patients in the control group (re-treatment with bypass surgery or angioplasty) and in one patient in the irradiation group (re-treatment with angioplasty) were re-treated. However, the rate of target vessel re-treatment, which included the re-treatment of target lesions, was higher in the irradiation group (four procedures in the irradiation group vs two in the control group at 24 months), mainly because of edge stenoses.
No complications related to endovascular irradiation (eg, aneurysm, pseudoaneurysm, or late thrombosis) were observed during the 2-year follow-up period.
The results of a number of studies have demonstrated the effectiveness of beta and gamma emitters in reducing the rate of restenosis after revascularization of coronary arteries. Only recently, though, have the results of randomized trials confirmed that intracoronary gamma irradiation (17–19) can facilitate reductions in both the numbers of recurrent in-stent stenoses and the numbers of in-stent restenoses in saphenous vein grafts in patients who have undergone coronary artery bypass surgery (20).
Compared with the number of clinical trials on endoluminal irradiation in coronary arteries, the number of trials investigating the effectiveness of endoluminal irradiation in femoropopliteal arteries is still limited. Nevertheless, the results of these trials are encouraging. Results of the Liermann et al (12) investigation, which to our knowledge was the first nonrandomized study on recurrent stenoses of femoropopliteal arteries after angioplasty, directional atherectomy, or stent placement, demonstrated a patency rate of 84% up to 7.5 years after endovascular gamma irradiation. In another study, the rate of restenosis of de novo or recurrent long femoropopliteal lesions was reduced from 53.7% to 28.3% by 6 months after PTA in patients who underwent noncentered endovascular irradiation (10). In a recently published nonrandomized pilot trial, the rate of restenosis after noncentered endovascular irradiation of dilated de novo femoropopliteal stenoses was 14% (21).
To our knowledge, the optimal radiation dose necessary to inhibit restenosis in femoropopliteal arteries has not yet been systematically investigated in dose-finding studies. However, the inhibitory effect of irradiation has proved to be dose dependent in both animal experiments (22–24) and clinical studies of coronary arteries (17). The results of published trials on femoropopliteal arteries suggest that a dose of 14 Gy delivered to the adventitia, as was used in our study and in the feasibility part of the Peripheral Arteries Radiation Investigational Study, or PARIS, trial (25), is more effective than a lower dose of 12 Gy at the intima. The restenosis rate was higher in the clinical trials in which endovascular irradiation was performed with the lower dose (10,11,21).
Dose inhomogeneity within the vessel wall may have an important role in the irradiation of femoropopliteal arteries owing to their large vessel diameter compared with the vessel diameter of coronary arteries. Poor centering of the radioactive source within the arterial lumen might cause some areas to receive a dose that is too low or too high, and, thus, it might unpredictably influence the effectiveness of the irradiation. In our trial, endovascular irradiation was performed with a segmented balloon catheter for source centering in femoropopliteal arteries. There are disadvantages to using the centering catheter, however. There is a risk of thromboembolic complications, and the need for an 8-F sheath for insertion of the centering catheter increases the risk for procedure-related complications.
Within 2 years after irradiation, we observed new stenoses at the proximal and distal edges of some of the irradiated vessel segments. Differences in rates of new stenoses were not significant between the two groups; however, there is the remaining question of whether the new stenoses in the irradiation group were so-called "candy-wrapper," or edge, stenoses or were due to atherosclerotic progression. The candy-wrapper, or edge, effect is well known from coronary studies (4,26–29). Candy-wrapper stenoses in coronary arteries usually develop earlier than the new stenoses in our study did. In our study, only one patient among the two groups had a new stenosis at the proximal edge of the irradiated vessel at 6-month follow-up.
Furthermore, the occurrence of edge stenoses was not described in other studies of peripheral arteries (10,11). However, in our study, the new lesions were isolated short stenoses that developed exactly at the edge of the irradiated segments. The edge effect was the reason that our study protocol dictated that the irradiated area (10 cm) had to be larger than the region of angioplasty (mean, 3.2 cm ± 2.5 in the irradiation group). It is well known from coronary studies that total restenosis rates are lower when the area of the irradiated segment significantly overlaps the area of the lesion (27,30). The larger the area of irradiation, the longer the centering balloon catheter remains inflated in the superficial femoral or popliteal artery; this factor might elevate the risk of thromboembolic complications. Given these issues of uncertainty, studies to investigate whether the area of irradiation can be reduced without facilitating a risk of incorrect irradiation application, or "geographic mismatch," and the induction of candy-wrapper stenoses are warranted.
The results of our 2-year follow-up study confirm that late thrombosis is not a problem that is associated with endovascular irradiation performed immediately after angioplasty of de novo femoropopliteal stenoses. This finding is in contrast to the reported 9% incidence of postirradiation late thrombosis in coronary arteries (19,31–34). We presume that the reason for this discrepancy is that angioplasty alone was the only endovascular treatment performed in our study. In coronary arteries, late thrombosis occurs mainly after stent placement and is attributed to a pronounced delay in endothelialization. The small number of patients in our study limited the wide applicability of the recommendation to prescribe only aspirin following angioplasty and irradiation.
Is endovascular irradiation indicated after angioplasty of de novo femoropopliteal stenoses? In the present study, about one-third of the patients in the control group developed recurrent stenoses of greater than 50%, but only two of these patients were symptomatic and were re-treated by means of bypass surgery or PTA. Thus, if endovascular irradiation had been performed in all of the patients in the control group, then 13 (87%) of these patients would have undergone irradiation unnecessarily—that is, without subsequently developing symptomatic restenosis. On the basis of this theory and the data gleaned in our study, and with the assumption that the effectiveness of endovascular irradiation is identical for de novo and recurrent stenoses, irradiation would be indicated only in those patients with symptomatic restenoses.
There were some limitations to our study. The first one was the relatively small number of patients. This was partly due to the results of our interim analysis (13), which prompted us not to perform additional randomizations of patients into irradiation and nonirradiation groups for ethical reasons. However, the small number of patients may be the reason that the interview and treadmill test results favored the irradiation group but were not significantly different between the two groups. Another limitation was the fact that the majority of stenoses in the study were short lesions. This may explain the more favorable outcomes in our study compared with the outcomes in other investigations (10,11).
A longer follow-up period would help to further assess the effectiveness of endovascular irradiation in peripheral arteries. It would be of interest to know whether the favorable effect of endovascular irradiation endures for longer follow-up periods, as was demonstrated in studies on peripheral arteries (12) and coronary arteries (35,36).
In conclusion, endovascular irradiation with a centered 192Ir gamma source performed immediately after angioplasty of de novo femoropopliteal stenoses results in significantly reduced degrees of stenosis of the target lesions up to 24 months after treatment but is associated with a risk of new stenoses. The benefit of endovascular irradiation was more significant early after PTA and was reduced at 24-month follow-up.
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FOOTNOTES |
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Abbreviation: PTA = percutaneous transluminal angioplasty
Author contributions: Guarantors of integrity of entire study, K.K., K.L.; study concepts and design, K.K., K.L., M.B.; literature research, K.K., D.S.; clinical studies, K.K., M.B., M.N., R.P.M.; data acquisition, K.K., K.L., M.Z., D.W., D.S.; data analysis/interpretation, K.K., K.L., M.Z.; statistical analysis, H.S., K.K.; manuscript preparation, K.K., D.S.; manuscript definition of intellectual content, K.K., M.B.; manuscript editing, K.K.; manuscript revision/review, K.K., K.L., H.S.; manuscript final version approval, K.K., K.L.
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) and control (
) groups before and shortly after PTA and at follow-up of up to 24 months are plotted. Results were significantly different between the two groups 3-12 months after PTA. (b) Graph illustrates ankle-brachial indexes at color duplex US. The mean ankle-brachial index was better in the irradiation group (
