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Intracoronary radiation therapy is effective in reducing the recurrence of in-stent stenosis in native coronary arteries. We examined the effects of intravascular gamma radiation in patients with in-stent restenosis of saphenous-vein bypass grafts.A total of 120 patients with in-stent restenosis in saphenous-vein grafts, the majority of whom had diffuse lesions, underwent balloon angioplasty, atherectomy, additional stenting, or a combination of these procedures. If the intervention was successful, the patients were randomly assigned in a double-blind fashion to intravascular treatment with a ribbon containing either iridium-192 or nonradioactive seeds. The prescribed dose, delivered at a distance of 2 mm from the source, was 14 to 15 Gy in vessels that were 2.5 to 4.0 mm in diameter and 18 Gy in vessels with a diameter that exceeded 4.0 mm. The primary end points were death from cardiac causes, Q-wave myocardial infarction, revascularization of the target vessel, and a composite of these events at 12 months.Revascularization and radiation therapy were successfully accomplished in all patients. At six months, the restenosis rate was lower in the 60 patients assigned to the iridium-192 group than in the 60 assigned to the placebo group (21 percent vs. 44 percent, P=0.005). At 12 months, the rate of revascularization of the target lesion was 70 percent lower in the iridium-192 group than in the placebo group (17 percent vs. 57 percent, P0.001), and the rate of major cardiac events was 49 percent lower (32 percent vs. 63 percent, P0.001).The results of our study support the use of gamma-radiation therapy for the treatment of in-stent restenosis in patients with bypass grafts.

Background: The Washington Radiation for In-Stent Restenosis Trial (WRIST) is a double-blinded randomized study evaluating the effects of intracoronary radiation therapy (IRT) in patients with in-stent restenosis (ISR). Methods: One hundred and thirty patients with ISR (100 native coronary and 30 vein grafts) underwent PTCA, laser ablation, rotational atherectomy, and/or additional stenting (36% of lesions). Patients were randomized to either Iridium-192 IRT or placebo, with a prescribed dose of 15 Gy to a 2-mm radial distance from the center of the source. Results: Angiographic restenosis (27% vs. 56%, P =.002) and target vessel revascularization (TVR; 26% vs. 66%, P P =.002) and TVR (IRT=17% vs. placebo=3%, P =.009). At 3 years, the major adverse cardiac event (MACE) rate was significantly reduced with IRT (39% vs. 65%, P =.003). Conclusions: In WRIST, patients with ISR treated with IRT using 192 Ir had a marked reduction in the need for repeat target lesion and vessel revascularization at 6 months, with the clinical benefit maintained at 3 years.

Background —Treatment of in-stent restenosis presents a critical limitation of intracoronary stent implantation. Ionizing radiation has been shown to decrease neointimal formation within stents in animal models and in initial clinical trials. We studied the effects of intracoronary γ-radiation therapy versus placebo on the clinical and angiographic outcomes of patients with in-stent restenosis. Methods and Results —One hundred thirty patients with in-stent restenosis underwent successful coronary intervention and were then blindly randomized to receive either intracoronary γ-radiation with 192 Ir (15 Gy) or placebo. Four independent core laboratories blinded to the treatment protocol analyzed the angiographic and intravascular ultrasound end points of restenosis. Procedural success and in-hospital and 30-day complications were similar among the groups. At 6 months, patients assigned to radiation therapy required less target lesion revascularization and target vessel revascularization (9 [13.8%] and 17 [26.2%], respectively) compared with patients assigned to placebo (41 [63.1%, P =0.0001] and 44 [67.7%, P =0.0001], respectively). Binary angiographic restenosis was lower in the irradiated group (19% versus 58% for placebo, P =0.001). Freedom from major cardiac events was lower in the radiation group (29.2% versus 67.7% for placebo, P Conclusions —Intracoronary γ-radiation used as adjunct therapy for patients with in-stent restenosis significantly reduces both angiographic and clinical restenosis.

Background— Intracoronary radiation therapy (IRT) is the only proven treatment for in-stent restenosis (ISR). It is, however, associated with a significant failure rate. The present study evaluated the outcomes of patients who underwent repeat intracoronary radiation for recurrent ISR. Methods and Results— Fifty-one consecutive patients who failed a previous radiation treatment, presented with angina and angiographic evidence of ISR, and were treated with percutaneous coronary intervention (PCI) and repeat radiation to the same segment were studied. Twenty-five patients were treated with gamma radiation in a dose of 15 Gy, and 26 were treated with beta radiation doses of 18.3 to 23 Gy. The mean cumulative dose for this cohort was 39.5±11.9 Gy (range, 29 to 75.6 Gy). The outcomes of those patients were compared with outcomes of 299 patients who also failed initial radiation but were treated with repeat conventional PCI to a previously irradiated segment without repeat radiation. At 9 months after treatment, the repeat-IRT group had lower rates of target lesion revascularization (23.5% versus 54.6%; P P Conclusions— Repeat gamma or beta radiation to treat failed IRT for ISR after conventional PCI is safe and effective at 9 months and should be considered as a therapeutic option for this difficult patient subset.

Background— The Washington Radiation for In-Stent Restenosis Trial for long lesions (Long WRIST) was designed to determine the safety and efficacy of vascular brachytherapy for the treatment of diffuse in-stent restenosis. Methods and Results— A total of 120 patients with diffuse in-stent restenosis in native coronary arteries (lesion length, 36 to 80 mm) were randomized for either radiation with 192 Ir with 15 Gy at 2 mm from the source axis or placebo. After enrollment, 120 additional patients with the same inclusion criteria were treated with 192 Ir with 18 Gy and included in the Long WRIST High Dose registry. Antiplatelet therapy was initially prescribed for 1 month and was extended to 6 months in the last 60 patients of the Long WRIST High Dose registry. At 6 months, the binary angiographic restenosis rate was 73%, 45%, and 38% in the placebo, 15 Gy, and 18 Gy radiated groups, respectively ( P P P Conclusions— Vascular brachytherapy with 192 Ir is safe and reduces the rate of recurrent restenosis in diffuse in-stent restenosis. The efficacy of vascular brachytherapy on angiographic and clinical outcomes is enhanced with a radiation dose of 18 Gy and prolonged antiplatelet therapy.

In-stent restenosis (ISR) is a major limitation of coronary stenting and is associated with high recurrence rates after intervention with all available devices. Intracoronary gamma (gamma) radiation was proved to reduce the recurrence rate after conventional therapy. The purpose of this study was to compare the different devices utilized for the treatment of ISR with and without gamma radiation. To search for the optimal device for the treatment of ISR, 685 patients from the radiation trials for ISR who were randomized to either iridium-192 gamma radiation (559 patients) or placebo (126 patients) following intervention were evaluated. Devices used included balloon percutaneous transluminal coronary angioplasty, excimer laser coronary angioplasty (ELCA), rotational atherectomy, and additional stent implantation. Baseline clinical and angiographic characteristics were similar between the gamma radiation and placebo groups. One- and 6-month clinical and angiographic outcomes were compared. The use of stenting compared with other devices was associated with increased late loss. Device selection used as adjunctive therapy did not influence the 30-day outcome. Patients treated with gamma radiation and placebo therapy had similar rates of composite major adverse coronary events (MACE) (death, Q-wave myocardial infarction, target vessel revascularization) (3% vs 2%, p = NS). At 6 months, MACE rates in irradiated patients were similar among POBA (29%), ELCA (28%), rotational atherectomy (18%), and additional stent implantation (30%, p = NS), and were significantly lower compared with placebo for the entire cohort and for each device subgroup. The overall recurrence rate of ISR was lower in patients treated with gamma radiation using iridium-192 compared with placebo. Device selection did not influence late clinical outcomes in irradiated and nonirradiated groups.

OBJECTIVESThis study was designed to analyze the in-hospital and six-month clinical and angiographic outcomes of patients with chronic renal failure (CRF) treated with intracoronary radiation for the prevention of recurrence of in-stent restenosis.BACKGROUNDPatients with CRF are at a higher risk than the general population for accelerated atherosclerotic cardiovascular disease and for restenosis after percutaneous coronary intervention. Previous studies have shown the effectiveness of both beta and gamma radiation in preventing recurrent restenosis in patients with in-stent restenosis.METHODSWe studied the in-hospital and six-month clinical and angiographic outcomes of 118 patients with CRF and 481 consecutive patients without CRF who were treated with intracoronary radiation for the prevention of recurrence of in-stent restenosis in native coronaries and saphenous vein grafts.RESULTSPatients with CRF were usually older, women, hypertensive and diabetic, with multivessel disease and with reduced left ventricular function. In-hospital outcome for patients with CRF was marred by a higher incidence of death, non–Q-wave myocardial infarction and major vascular and bleeding complications. At six-month follow-up, the mortality rate was higher in patients with CRF, 7.6% compared with 1.9% in non-CRF patients (p = 0.003). Restenosis, target lesion revascularization (TLR) and target vessel revascularization (TVR) rates were similar in the two groups. In patients with CRF, radiation therapy compared to placebo reduced restenosis (53.8% vs. 22.6%, p = 0.04), TLR (71.4% vs. 15.3%, p < 0.0001) and TVR (78.6% vs. 23.7%, p = 0.0002).CONCLUSIONSIntracoronary radiation for the prevention of recurrence of in-stent restenosis achieved similar rates of restenosis and revascularization procedures in patients with and without CRF. Despite this benefit, patients with renal dysfunction continued to have significantly higher in-hospital and six-month adverse outcomes.

Background —Intracoronary γ-radiation reduces recurrent in-stent restenosis. Late thrombosis (>30 days after radiation therapy) is identified as a serious complication. The Washington Radiation for In-Stent Restenosis Trial (WRIST) PLUS, which involved 6 months of treatment with clopidogrel and aspirin, was designed to examine the efficacy and safety of prolonged antiplatelet therapy for the prevention of late thrombosis. Methods and Results —A total of 120 consecutive patients with diffuse in-stent restenosis in native coronary arteries and vein grafts with lesions 192 Ir seeds was positioned to cover the treated site, and a dose of 14 Gy to 2 mm was prescribed. Patients were discharged with clopidogrel and aspirin for 6 months and followed angiographically and clinically. All patients but one tolerated the clopidogrel. The late occlusion and thrombosis rates were compared with the γ-radiation–treated (n=125) and the placebo patients (n=126) from the WRIST and LONG WRIST studies (which involved only 1 month of antiplatelet therapy). At 6 months, the group receiving prolonged antiplatelet therapy had total occlusion and late thrombosis rates of 5.8% and 2.5%, respectively; these rates were lower than those in the active γ-radiation group and similar to those in the placebo historical control group. Conclusions —Six months of clopidogrel and aspirin and a reduction in re-stenting for patients with in-stent restenosis treated with γ-radiation is well tolerated and associated with a reduction in the late thrombosis rate compared with a similar cohort treated with only 1 month of clopidogrel and aspirin.

External megavoltage irradiation has been utilized alone or in combination with surgery, 131I therapy, interstitial radiation, chemotherapy and hyperthermia to produce cure or improved local—regional control. The optimal sequencing of these effective modalities continues to be evaluated in clinical trials and clinical practice. New methods of time-dose relationships including hyperfractionation, hypofractionation, and high-dose fractions are currently under clinical evaluation. The use of interstitial irradiation, in experienced hands, as an addition to standard treatment modalities has produced good results in a limited number of patients with thyroid carcinoma. Hyperthermia is potentially applicable to all cancers, including thyroid carcinoma. The clinical research with hyperthermia so far has demonstrated the best results when hyperthermia is combined with external irradiation.