Two-year follow-up after catheter-based radiotherapy to inhibit coronary restenosis.

BACKGROUND: Although early trials indicate the treatment of restenosis with radiation therapy is safe and effective, the long-term impact of this new technology has been questioned. The possibility of late untoward consequences, such as aneurysm formation, perforation, and accelerated vascular disease, is of significant concern. Furthermore, it is not known whether the beneficial effects of radiation therapy will be durable or whether radiation will only delay restenosis. METHODS AND RESULTS: A double-blind, randomized trial was undertaken to compare 192Ir with placebo sources in patients with previous restenosis after coronary angioplasty. Patients were randomly assigned to receive a 0.76-mm (0. 03-in) ribbon containing sealed sources of either 192Ir or placebo. All patients underwent repeat coronary angiography at 6 months. All living patients were contacted 24 months after their index study procedure. Patients were assessed with respect to the need for target-lesion revascularization or nontarget-lesion revascularization, occurrence of myocardial infarction, or death. Over a 9-month period, 55 patients were enrolled; 26 were randomized to 192Ir and 29 to placebo. Follow-up was obtained in 100% of living patients at a minimum of 24 months. Target-lesion revascularization was significantly lower in the 192Ir group (15.4% versus 44.8%; P<0. 01). Nontarget-lesion revascularization was similar in 192Ir and placebo patients (19.2% versus 20.7%; P=NS). There were 2 deaths in each group. The composite end point of death, myocardial infarction, or target-lesion revascularization was significantly lower in 192Ir-treated versus placebo-treated patients (23.1% versus 51.7%; P=0.03). No patient in the 192Ir group sustained a target-lesion revascularization later than 10 months. CONCLUSIONS: At 2-year clinical follow-up, treatment with 192Ir demonstrates significant clinical benefit. Although further follow-up (including late angiography) will be necessary, no clinical events have occurred to date in the 192Ir group to suggest major untoward effects of vascular radiotherapy. At the intermediate follow-up time point, vascular radiotherapy continues to be a promising new treatment for restenosis.

Three-year clinical and angiographic follow-up after intracoronary radiation : results of a randomized clinical trial.

BACKGROUND: Although several early trials indicate treatment of restenosis with radiation therapy is safe and effective, the long-term impact of this new technology has been questioned. The objective of this report is to document angiographic and clinical outcome 3 years after treatment of restenotic stented coronary arteries with catheter-based (192)Ir. METHODS AND RESULTS: A double-blind, randomized trial compared (192)Ir with placebo sources in patients with previous restenosis after coronary angioplasty. Over a 9-month period, 55 patients were enrolled; 26 were randomized to (192)Ir and 29 to placebo. At 3-year follow-up, target-lesion revascularization was significantly lower in the (192)Ir group (15. 4% versus 48.3%; P<0.01). The dichotomous restenosis rate at 3-year follow-up was also significantly lower in (192)Ir patients (33% versus 64%; P<0.05). In a subgroup of patients with 3-year angiographic follow-up not subjected to target-lesion revascularization by the 6-month angiogram, the mean minimal luminal diameter between 6 months and 3 years decreased from 2.49+/-0.81 to 2.12+/-0.73 mm in (192)Ir patients but was unchanged in placebo patients. CONCLUSIONS: The early clinical benefits observed after treatment of coronary restenosis with (192)Ir appear durable at late follow-up. Angiographic restenosis continues to be significantly reduced in (192)Ir-treated patients, but a small amount of late loss was observed between the 6-month and 3-year follow-up time points. No events occurred in the (192)Ir group to suggest major untoward effects of vascular radiotherapy. At 3-year follow-up, vascular radiotherapy continues to be a promising new treatment for restenosis.

Derivation of isoeffect dose rate for low-dose-rate brachytherapy and external beam irradiation.

PURPOSE: The combination of external beam irradiation and brachytherapy has been used effectively in the management of many malignancies. Brachytherapy dose is typically prescribed to an isodose rate line, from which the implant duration is derived. In this study, the linear-quadratic model is used to derive the brachytherapy dose rate at which biological effectiveness is equivalent to that of external beam irradiation. METHODS AND MATERIALS: Relative effectiveness per unit dose (RE) for brachytherapy was based on Dale's formalism. Isoeffect dose rate, defined as the brachytherapy dose rate at which the biological effectiveness is equivalent to that of external beam irradiation, was derived. RESULTS: The functional dependencies of brachytherapy RE on dose rate, alpha/beta ratio, and implant duration were investigated. The isoeffect dose rate depends only on the dose per fraction, sublethal damage repair (SLDR) constant, and the implant duration. The isoeffect dose rate does not depend on alpha/beta ratio. For sufficiently long implant duration >10-15 hours, the value for isoeffect dose rate approaches a constant value around 40 to 50 cGy/hr. CONCLUSION: The isoeffect dose rate may be useful in treatment planning and optimization for low-dose-rate (LDR) brachytherapy, especially when brachytherapy is used in combination with external beam irradiation.

Barotrauma due to stent deployment in endovascular brachytherapy for restenosis prevention.

PURPOSE: In this study, the effect of barotrauma due to stent deployment is investigated for several commonly used commercial stents used in endovascular brachytherapy for restenosis prevention. METHODS AND MATERIALS: Restenosis due to intimal hyperplasia can occur anywhere along the clinical target volume, which is defined as the length of vessel receiving intervention or injury. The injury may be due to angioplasty, atherectomy (tissue removing), stenting, and stent deployment. Manufacturer specifications for several commonly used stents were reviewed and the results were tabulated. RESULTS: The barotrauma length of stents reviewed in this study ranges from 0.5 to 2.5 mm; the average was 1.7 mm. CONCLUSIONS: By considering specific barotrauma into the treatment length, one can provide adequate treatment margins to minimize edge failure or to avoid "geographic miss," which may improve the efficacy of endovascular brachytherapy.

Prognostic factors in adult soft-tissue sarcomas of the head and neck.

PURPOSE: The main objectives of this study were (a) to review the treatment results of primary head and neck soft-tissue sarcoma at our institution, (b) to identify important prognostic factors in local control and survival, and (c) to assess the efficacy of salvage therapy. METHODS AND MATERIALS: Sixty-five patients were treated at the University of California, San Francisco, between 1961 and 1993. Seventeen patients (27%) had low-grade, 10 (15%) had intermediate-grade, and 38 (58%) had high-grade sarcomas. Tumors were > 5 cm in 35 patients. Local management consisted of surgery alone in 14 patients (22%), surgery and radiotherapy in 40 (61%), and radiotherapy alone in 11 (17%) patients. The median follow-up was 64 months. RESULTS: The 5-year actuarial local control rate of the entire group was 66%. Tumor size and grade were important predictors for local control on multivariate analysis. The actuarial local control rate at 5 years was 92% for T1 vs. 40% for T2 primaries (p = 0.004), and 80% for Grade 1-2 vs. 48% for Grade 3 tumors (p = 0.01). None of the patients treated with radiotherapy alone with a dose of 50-65 Gy were controlled locally. Combined radiotherapy and surgery appeared to yield superior local control compared to surgery alone (77% vs. 59%); however, the difference was not statistically significant. The 5-year actuarial overall and cause-specific survivals were 56% and 60%, respectively. Unfavorable prognostic factors for cause-specific survival on multivariate analysis were age > 55 (p = 0.009), high tumor grade (p = 0.0002), inadequate surgery (p = 0.008), and positive surgical margins (p = 0.0009). In patients who underwent salvage therapy for treatment failure, the 5-year actuarial survival after salvage treatment was 26%. CONCLUSION: Tumor size and grade were important predictors for local control. Age, grade, adequacy of surgery, and status of surgical margins were significant prognostic factors for survival. There was a trend of improved local control with combined surgery and radiotherapy compared to either modality alone for high-risk patients. Radiotherapy alone with doses < or = 65 Gy was insufficient for control of gross disease. Aggressive salvage therapy was worthwhile in patients whose disease was uncontrolled after the initial treatment.

A comparison of misonidazole sensitized radiation therapy to radiation therapy alone for the palliation of hepatic metastases: results of a Radiation Therapy Oncology Group randomized prospective trial.

Between May 1980 and July 1983, the RTOG conducted a randomized prospective study comparing external radiation therapy and misonidazole to radiation therapy alone for patients with hepatic metastases. Two hundred fourteen patients were accessioned to this study of whom 187 were evaluable. Radiation therapy was delivered to the whole liver to a dose of 21.0 Gy in 7 fractions. Misonidazole was administered orally, 1.5 gm/m2 daily 4-6 hr before each treatment. Patients in the two treatment groups were evenly distributed with respect to stratification variables including primary site, extent of metastatic disease, and Karnofsky Performance Score (KPS). End points examined included amelioration of hepatic pain, improvement of KPS and alkaline phosphatase, decrease in liver and tumor size, and survival. The addition of misonidazole did not significantly improve the therapeutic response to radiation therapy in any of the parameters studied. Hepatic irradiation was effective in relieving abdominal pain with 80% of the symptomatic patients achieving improvement following therapy. Pain was completely relieved in 54% of these patients. Patients with liver metastases from colon carcinoma improved more frequently than those with metastases from other primary tumor sites (p = 0.02). Relief of pain occurred more frequently in patients treated with radiation therapy and misonidazole (87%) compared with radiation therapy alone (74%) (p = 0.08). Palliation of pain was prompt, occurring within a median of 1.7 weeks from the initiation of treatment, and 94% of patients who improved did so within 6 weeks of treatment. The median duration of response was 13.0 weeks in the symptomatic patients; 52% of those surviving 3 months remained improved. KPS improved in 28% of patients. Serial CT scans revealed a partial response in 7% and a marginal response in 13% of patients. One patient had a complete response to treatment. The median survival of patients treated in this series was 4.2 months with no difference between the two treatment groups. Patients with metastases from colon carcinoma and an initial KPS of 80 or more (48% of the patient population) had a median survival of 5.8 months with radiation therapy alone compared with 6.6 months with radiation therapy and misonidazole (p = 0.36). There was no significant treatment related morbidity. Radiation therapy remains an excellent palliative tool for the management of patients with symptomatic hepatic metastases. Further research must continue to identify new methods of selectivity enhancing the tumor response to radiation therapy.

A subgroup analysis of the Scripps Coronary Radiation to Inhibit Proliferation Poststenting Trial.

INTRODUCTION: In the Scripps Coronary Radiation to Inhibit Proliferation Poststenting (SCRIPPS) Trial, 192Ir significantly reduced angiographic, ultrasonographic, and clinical endpoints of restenosis. The objective of this analysis was to quantitate the impact of patient, lesion and technical characteristics on late angiographic outcome. METHODS: Patients with restenotic, stented coronary lesions were randomized to receive either 192Ir or placebo sources. Late luminal loss and loss index were calculated for several patient subgroups, including patients with diabetes, in-stent restenosis, multiple previous percutaneous transluminal coronary angioplasty (PTCA) procedures, longer lesion lengths, saphenous vein grafts, small vessel diameters, and minimum dose exposures < 8.00 Gy. Two-factor analysis of variance was used to test for an interaction between patient characteristics and treatment effect. RESULTS: In the treated group, late loss was particularly low in patients with diabetes (0.19 mm), in-stent restenosis (0.17 mm), reference vessel diameters < 3.0 mm (0.07 mm), and patients who received a minimum radiation dose to the entire adventitial border of at least 8.00 Gy. The loss index in each of these subgroups was similarly low at -0.02, 0.03, -0.02, and 0.03, respectively. By 2-factor analysis of variance, a significant interaction between subgroup characteristic and treatment effect (late loss) was found in patients with in-stent restenosis (p = 0.035), and patients receiving a minimum dose of 8.00 Gy to the adventitial border (p = 0.009). CONCLUSION: In this pilot study, patient characteristics associated with a more aggressive proliferative response to injury appeared to confer an enhanced response to radiotherapy. Furthermore, a dose threshold response to 192Ir was found with an enhanced response occurring when the entire circumference of the adventitial border was exposed to at least 8.00 Gy.

Quantitative angiographic analysis of stent restenosis in the Scripps Coronary Radiation to Inhibit Intimal Proliferation Post Stenting (SCRIPPS) Trial.

To identify luminal dimension changes occurring within the stent alone and within the stent + margin segment, we reviewed the quantitative angiographic results obtained from the Scripps Coronary Radiation to Inhibit Proliferation Post Stenting (SCRIPPS) trial, a prospective randomized trial assessing the effect of iridium-192 (Ir-192) on the prevention of stent restenosis. Fifty-five patients were randomly assigned to receive Ir-192 or placebo sources after successful intervention. Procedural and 6-month follow-up cineangiograms were quantitatively reviewed in 52 patients to identify changes within the stent and the stent + margin segment. The percent diameter stenosis was lower within the stent than within the stent + margin segment after the procedure (6 +/- 22% vs 21+/- 15%, p <0.0001) and at follow-up (28 +/- 29% vs 42 +/- 21%, p <0.0001). As a result, a lower restenosis rate was found within the stent than within the stent + margin (25% vs 37%, p <0.0001); isolated stent margin restenosis occurred in 11.5% of lesions. Treatment with Ir-192 reduced restenosis within the stent (8% vs 39%; p = 0.010) and within the stent + margin segment (17% vs 54%; p = 0.010); the reduction in restenosis at the margin only (8.3% vs 14.3%, p = 0.503) was not significant. The lowest relative risk for restenosis resulting from Ir-192 occurred within the stent (0.21; 95% confidence interval [CI] 0.05 to 0.86) compared with the stent + margin segment (0.31; 95% CI 0.12 to 0.81) or the stent margin (0.58; 95% CI 0.12 to 2.91). In the SCRIPPS trial, 32% of restenosis occurred at the stent margins. Treatment with Ir-192 reduced restenosis primarily within the stent rather than the margin. Whether extending the treatment length to fully include the stent margins will further reduce restenosis requires further study.

Radiation therapy to inhibit restenosis: early clinical results.

BACKGROUND: Although several early trials indicate that treatment of restenosis with radiation therapy is safe and effective, the long-term impact of this new technology has been questioned. The objective of this report is to document angiographic and clinical outcome 3 years after treatment of restenosis of stented coronary arteries with catheter-based iridium-192 (192Ir). METHODS: A double-blind, randomized trial compared 192Ir with placebo sources in patients with previous restenosis after coronary angioplasty. Over a 9-month period, 55 patients were enrolled; 26 were randomized to 192Ir and 29 to placebo. RESULTS: At 3-year follow-up, target-lesion revascularization was significantly lower in the 192Ir group (15.4% vs. 48.3%; p < 0.01). The dichotomous restenosis rate at 3-year follow-up was also significantly lower in 192Ir patients (33% vs. 64%; p < 0.05). In a subgroup of patients with 3-year angiographic follow-up not subjected to target-lesion revascularization by the 6-month angiogram, the mean minimal luminal diameter between 6 months and 3 years decreased from 2.49 +/- 0.81 mm to 2.12 +/- 0.73 mm in 192Ir patients, but was unchanged in placebo patients. CONCLUSIONS: The early clinical benefits observed after treatment of coronary restenosis with 192Ir appear durable at late follow-up. Angiographic restenosis continues to be significantly reduced in 192Ir-treated patients, but a small amount of late loss was observed between the 6-month and 3-year follow-up time points. No events occurred in the 192Ir group to suggest major untoward effects of vascular radiotherapy. At 3-year follow-up, vascular radiotherapy continues to be a promising new treatment for restenosis.

Initial studies with gamma radiotherpay to inhibit coronary restenosis.

BACKGROUND: Early studies indicate brachytherapy is a potential clinical treamtent for restenosis after coronary angioplasty procedures. The objective of this study was to evaluate the safety and efficacy of gamma radiation plus stenting in patients' previous restenosis. METHODS: In patients with previous coronary restenosis, balloon dilatation and/or coronary stenting was undertaken and then patients were randomly assigned to receive either Iridium-192 or placebo. Quantitative coronary angiographic, intravascular ultrasonographic, and clinical follow-up was obtained. RESULTS: Of the 55 patients enrolled, 26 were treated with Iridium-192 and 29 were in the placebo group. Late luminal loss was significantly lower in the treated group compared to the placebo group (0.38 +/- 1.06 mm vs. 1.03 +/- 0.97 mm, p = 0.03). Restenosis (stenosis of > or = 50% at follow-up) was found in 17% of treated patients compared to 54% of placebo patients (p = 0.01). The need for target lesion revascularization was observed in 12% of patients in the treated group compared to 45% in the placebo group (p = 0.01). CONCLUSIONS: In this initial trial, at 12 months follow-up, patients with previous restenosis were benefited by catheter-based gamma radiation therapy.

Theoretical assessment of dose-rate effect in endovascular brachytherapy.

PURPOSE: Several prospective randomized clinical trials utilizing endovascular brachytherapy after coronary angioplasty have shown promising preliminary results. Numerous clinical trials have been initiated to evaluate different delivery systems and source types. In this study, the dose-rate effect is investigated using a biophysical model derived from linear-quadratic formalism. MATERIALS AND METHODS: The dose-rate effect is quantified using the Dale's formulation, which is based on a linear-quadratic model. This model converts the total absorbed dose into the biological equivalent dose (BED) based on the dose rate, total dose, treatment duration, biological endpoint (alpha/beta ratio), and sublethal damage repair constant. The calculations are performed for two common source configurations used in current clinical trials (192Ir and 90Sr/Y). RESULTS: At smaller radial distance, the dose rate is higher, hence BED increases due to the increase in the relative effectiveness per unit dose (RE) and absorbed dose for a given treatment duration. For 90Sr/Y source, a similar trend is observed; however, it is at a much greater magnitude. The RE for 192Ir is close to unity, which is equivalent to that of external beam irradiation. CONCLUSION: Although current clinical trials in endovascular brachytherapy report similar absorbed dose, the biological effects may be different due to the extremely high gradient of dose rate near the sources, a variety of isotopes and delivery systems, and different dose prescriptions. If the theoretical predictions in this study are validated in clinical trials, the proposed model can be useful to compare different protocols, design new delivery systems and isotopes, and optimize how radiation is delivered.

Theoretical assessment of late cardiac complication from endovascular brachytherapy for restenosis prevention.

PURPOSE: In this study, a theoretical assessment of late cardiac complication from endovascular brachytherapy is performed using the integrated logistic model. MATERIALS AND METHODS: Calculation were performed for various lengths of Ir-192 sources using alpha/beta = 3.2 for the endpoint of chronic ischemia, TD50/5 = 7,000 cGy, and TD5/5 = 5,000 cGy. The dose distribution over a standard heart was divided into volume elements with uniform dose (dose-volume histogram). Using linear-quadratic equation, the dose in each of the volume elements was converted into dose equivalent to standard fractionation external beam irradiation. The normal tissue complication probability (NTCP) for each volume element was calculated and combined together to arrive at the cumulative risk of late cardiac complication. The NTCP was plotted against the dose prescribed at 2-mm radial distance for four treatment lengths. RESULTS: (1) The overall risk of late cardiac toxicity (chronic ischemia within 5 years) was estimated to be less than 1% for current clinical trials using Ir-192. (2) There is a volume effect with higher risk for larger irradiated volume, which can come from longer treatment time, the same dose prescribed at a greater radial distance, and a longer source train. (3) The NTCP vs. dose demonstrates a sigmoidal relationship. There is a threshold dose (about 500 cGy), below which the risk is minimal; the gradient of the curve is greater for longer treatment length. CONCLUSION: If the prediction from this model is validated with clinical data, it will contribute to guidelines for dose prescription, dose escalation, evaluation of new source design, and multivessel treatment.

Merkel cell carcinoma: review of 22 cases with surgical, pathologic, and therapeutic considerations.

BACKGROUND: Merkel cell carcinoma is a primary small blue cell tumor of the skin with a proclivity to metastasize. Surgery and radiation therapy have defined roles in the primary treatment of Merkel cell carcinoma. Systemic chemotherapy can produce good response rates but does not have a primary role in the management of nondisseminated Merkel cell carcinoma patients. METHODS: Twenty-two patients were identified over the last 10 years in a retrospective analysis of tumor registries from the 6 hospitals of the ScrippsHealth facilities. Hospital and clinic charts as well as pathology specimens were reviewed. RESULTS: Eight patients underwent Mohs' surgery with permanent tissue technique. None of these patients had a subsequent local recurrence. Six patients received adjuvant radiation therapy, only one of whom developed a disease recurrence within a radiation port. Systemic chemotherapy was given to seven patients. One patient did not accept further treatment after a punch biopsy. CONCLUSIONS: Merkel cell carcinoma is an aggressive primary neoplasm of the skin, the histologic diagnosis of which can be difficult. Mohs' surgical technique combined with radiation therapy provides excellent local control. Systemic treatment is associated with high response rates, but to the authors' knowledge durable responses are uncommon.

Physics and safety aspects of a coronary irradiation pilot study to inhibit restenosis using manually loaded 192Ir ribbons.

Radiation therapy has been successfully used in controlling some forms of benign tissue growth. A pilot study has been launched to evaluate the usefulness of localized radiation therapy in reducing restenosis after coronary angioplasty. In this randomized, double-blind study, patients with known restenosis received balloon angioplasty or additional stent implantation and were then randomized to receive either radiation or placebo treatment. Active sources consisted of 192Ir in the form of cylindrical seeds (0.3 x 0.05 cm). The seeds are embedded in a nylon ribbon. The nylon ribbon is passed through an indwelling coronary catheter. For this pilot trial, radioactive sources were exposed to blood elements and, therefore, required sterilization. A method of sterilization is described. A working team was developed to perform coronary radiation procedures at our institution. A description of the procedure is provided.

How long is enough? Defining the treatment length in endovascular brachytherapy.

The International Commission on Radiation Units and Measurement (IRCU) 50 has clearly defined treatment volumes in radiation therapy in the management of neoplasms. These concepts are applied to the field of endovascular brachytherapy (EVBT) for the prevention of postangioplasty restenosis. The following definitions are proposed: gross target length (GTL) is defined as the narrowed segment of the artery that requires intervention. Clinical target length (CTL) is defined as the intervened or injured length, which could be due to angioplasty, stent strut injury, stent deployment, or debulking procedures. Planning target length (PTL) is the CTL plus a margin to account for heart/catheter movement and uncertainty in target localization. The final treatment length (TL) is the PTL plus the effect of penumbra. The accurate specification of treatment length serves several important purposes. Based on an understanding of the different factors constituting the treatment length, adequate margins can be provided beyond the GTL; this will avoid geographic misses and minimize edge failures. These definitions of target length ensure treatment consistency and provide a standard terminology for communication among practitioners of EVBT, something of critical importance in the conduct of multi-institutional trials in this new and multidisciplinary therapy. Finally, since the efficacy of EVBT is critically dependent on the precision of radiation delivery, these guidelines ensure that the benefits of EVBT seen in prospective randomized trials can be translated into daily clinical practice at the community level.

Early lumen loss after repeat coronary intervention for in-stent restenosis.

The purpose of this study was to compare the effects of balloon angioplasty versus repeat stenting on the early angiographic outcome in patients with in-stent restenosis. The treatment of in-stent restenosis using balloon angioplasty alone often yields excellent early results, but is associated with a high rate of late recurrence. In the SCRIPPS trial, patients with restenosis were treated either with balloon angioplasty alone or placement of additional stents to optimize angiographic results before randomization and exposure of the restenotic segment to gamma radiation or placebo. In patients undergoing repeat catheter based intervention for the treatment of in-stent restenosis, quantitative coronary angiography was used to compare the results of balloon angioplasty alone versus repeat stenting on early lumen loss. After a mean delay time interval of 71 min, the early loss was 0.35 +/- 0.34 mm in the balloon angioplasty alone group compared to 0.01 +/- 0.34 mm in the repeat-stenting group (P = 0.004). The early loss index in the balloon angioplasty alone group (12.8 +/- 12.9%) was significantly greater than in the repeat stenting group (0.7 +/- 12.1%; P = 0.003). Although balloon angioplasty for in-stent restenosis often provides excellent immediate angiographic results, luminal diameters are significantly reduced in the early time period after balloon dilatation. Repeat stenting nearly abolishes this early luminal loss.

Catheter-based radiotherapy to inhibit restenosis after coronary stenting.

BACKGROUND: In animal models of coronary restenosis, intracoronary radiotherapy has been shown to reduce the intimal hyperplasia that is a part of restenosis. We studied the safety and efficacy of catheter-based intracoronary gamma radiation plus stenting to reduce coronary restenosis in patients with previous restenosis. METHODS: Patients with restenosis underwent coronary stenting, as required, and balloon dilation and were then randomly assigned to receive catheter-based irradiation with iridium-192 or placebo. Clinical follow-up was performed, with quantitative coronary angiographic and intravascular ultrasonographic measurements at six months. RESULTS: Fifty-five patients were enrolled; 26 were assigned to the iridium-192 group and 29 to the placebo group. Angiographic studies were performed in 53 patients (96 percent) at a mean (+/-SD) of 6.7+/-2.2 months. The mean minimal luminal diameter at follow-up was larger in the iridium-192 group than in the placebo group (2.43+/-0.78 mm vs. 1.85+/-0.89 mm, P=0.02). Late luminal loss was significantly lower in the iridium-192 group than in the placebo group (0.38+/-1.06 mm vs. 1.03+/-0.97 mm, P=0.03). Angiographically identified restenosis (stenosis of 50 percent or more of the luminal diameter at follow-up) occurred in 17 percent of the patients in the iridium-192 group, as compared with 54 percent of those in the placebo group (P= 0.01). There were no apparent complications of the treatment. CONCLUSIONS: In this preliminary, short-term study of patients with previous coronary restenosis, coronary stenting followed by catheter-based intracoronary radiotherapy substantially reduced the rate of subsequent restenosis.