Intracoronary beta-irradiation for the treatment of de novo lesions: 5-year clinical follow-up of the BetAce randomized trial.

BACKGROUND: Vascular brachytherapy (VBT) has been used for the prevention of restenosis. Despite initial positive results, long-term follow-up has shown a progressive loss of benefit in clinical outcome after beta-irradiation. We report the 5-year follow-up of the BetAce trial. METHODS: This prospective, randomized, single-blind trial included 61 patients treated for 64 de novo coronary lesions: 31 patients (33 stenoses) were treated with bare metal stents (control group), and 30 patients (31 stenoses) were treated with intracoronary beta-irradiation at the time of stented angioplasty (VBT group). RESULTS: Baseline and procedural data were similar between treatment arms. At 6 months, VBT reduced the need for target vessel revascularization (13% vs 35.5%, P = .04), but there was no significant difference in the 6- and 12-month event-free survival when clinical events were ranked. Between 1 and 5 years, an increasing number of target vessel failures was observed in both groups, leading to a similar long-term clinical outcome at 5 years (event-free survival 43% and 45% in the VBT and control groups, respectively, log-rank 0.001, P = .9). CONCLUSIONS: Beta-irradiation in de novo coronary lesions significantly reduced in-stent recurrences at 6 months compared with standard procedures. However, this initial benefit was not sustained in the long term. The results of this randomized study confirm the delayed and progressive restenotic process after beta-irradiation and stent implantation in de novo lesions.

Recommendations on detectors and quality control procedures for brachytherapy beta sources.

BACKGROUND AND PURPOSE: It is estimated that one third of the institutes applying clinical beta sources does not perform independent dosimetry. The Netherlands commission on radiation dosimetry (NCS) recently published recommended quality control procedures and detectors for the dosimetry of beta sources. The main issues of NCS Report 14 are summarized here. MATERIALS AND METHODS: A dosimetry survey was performed among 23 institutes in The Netherlands and Belgium. Well ionization chambers, a plastic scintillator, plane-parallel ionization chamber, diode and radiochromic film were used for determination of source strength (dose rate at reference distance) and uniformity of intravascular and ophthalmic sources. The source strength of multiple sources of each type was measured and compared with the source strength specified by the manufacturer. RESULTS: The standard deviation of the difference between measured and specified source strength was mostly about 3%, but varied between 0.8 and 15.8% depending on factors such as source type, detector, phantom and manufacturers calibration. The average non-uniformity was about 7% for intravascular sources and 20% for ophthalmic sources. It is estimated that the total relative standard uncertainty can be kept below +/-4% (1 sigma) with all detectors tested. Maximum deviations in source strength of 10% and a non-uniformity below 10% (intravascular) and 30% (ophthalmic) are recommended. CONCLUSIONS: Dosimetric and non-dosimetric quality control procedures on beta sources are recommended. They enable standardized measurements, including the determination of relative source strength and non-uniformity. Absolute calibrations depend on the future introduction of primary standards for clinical beta sources.

Intracoronary beta-irradiation prevents excessive in-stent neointimal proliferation in de novo lesions of patients with high plasma ACE levels. The BetAce randomized trial.

BACKGROUND: This study evaluated vascular brachytherapy (VBT) as a potent antiproliferative treatment to prevent in-stent restenosis (ISR) after coronary angioplasty of de novo lesions in patients carrying the D allele of the I/D polymorphism of the ACE gene and high ACE plasma levels (>34 U/l). METHODS AND MATERIALS: A prospective randomized trial was designed to detect a 30% improvement in the minimal lumen diameter (MLD) of the stenotic artery, as measured by quantitative coronary analysis (QCA), 6 months following VBT at the time of stented angioplasty. All patients were carriers of the D allele of the ACE gene, with plasma ACE levels >34 U/l. RESULTS: Thirty-one patients (33 stenoses) were allocated to stent implantation (control group) and 30 patients (31 stenoses) to VBT and stented angioplasty. After angioplasty, in-stent MLD was similar in the two groups. At 6 months in the control group, in-stent MLD had decreased to 1.74+/-0.8 versus 2.25+/-1.05 mm in the VBT group (P=.04). The mean in-stent diameter was 2.3+/-0.8 mm in the control group versus 2.9+/-1.05 mm after VBT (P=.02), and the restenosis rate was 37.5% versus 17.9%, respectively (P=.08). At 6 months, a higher need for target vessel revascularization (TVR) was observed in the control group: 35.5% versus 13.3% (P=.04). CONCLUSIONS: This randomized study confirms that patients with high plasma ACE concentrations are exposed to an increased risk for ISR after coronary stenting. The preventive use of VBT in these patients reduced neointimal formation by 65% such that the MLD at follow-up was increased by 29% compared with the control group.

Angiographic and three-dimensional intravascular ultrasound analysis of combined intracoronary beta radiation and self-expanding stent implantation in human coronary arteries.

This study tested the combination of vascular brachytherapy (VBT) and self-expanding Wallstent implantation in coronary lesions of patients at high risk for restenosis as assessed angiographically by quantitative coronary analysis and by 3-dimensional intravascular ultrasound analysis. Twenty-nine "de novo" lesions were managed with a self-expanding stent alone (n = 19) or with a self-expanding stent after beta-VBT (n = 10) in 27 patients who had been identified by high levels of plasma angiotensin-converting enzyme as being prone to myointimal growth after stent implantation. At 6 months, the increase in stent strut diameter was similar in the 2 groups by quantitative coronary analysis and 3-dimensional intravascular ultrasound (Delta mean stent strut diameter -0.33 +/- 0.3 vs -0.40 +/- 0.3 mm, p = 0.5; Delta stent area -11.8 +/- 6.1 vs -12.0 +/- 6.1 mm(2), p = 0.9; Delta stent volume -96.9 +/- 112 vs -83.5 +/- 73 mm(3), p = 0.7; for groups treated with VBT and self-expanding stents and only self-expanding stents, respectively). In-stent neointimal proliferation was decreased in the group treated with VBT and self-expanding stents (minimal luminal diameter 2.5 +/- 0.8 vs 1.88 +/- 0.8 mm, p = 0.04) by quantitative coronary analysis (minimal luminal area 6.7 +/- 2.5 vs 4.1 +/- 1.9 mm(2), p = 0.01), by intravascular ultrasound, and proliferation volume (84.6 +/- 66.4 vs 159.2 +/- 103.5 mm(3), p = 0.05) by 3-dimensional intravascular ultrasound. Positive vessel and luminal remodelings were observed in 50% of the group treated with VBT and self-expanding stents and in 11% of the group treated only with self-expanding stents (p = 0.02). The combined use of VBT and self-expanding stents is a novel approach that enlarges vascular lumen by preventing vessel constriction and neointimal proliferation. The feasibility and good results of this experimental approach suggest that the simultaneous use of these 2 technologies may be an interesting alternative for difficult vascular districts with high restenosis rates, such as peripheral circulation in the lower limbs.

Dose distributions for 90Y intravascular brachytherapy sources used with balloon catheters.

The dose distribution around an intravascular brachytherapy 90Y line source with centering balloon catheters was measured with a plastic scintillator, TLD and radiochromic film. The absolute dose rates measured with the three detectors in a solid water phantom at 1, 2 and 3 mm distance from the centering balloon surfaces are in agreement within 3.5%, when the detectors are calibrated with the same 90Sr/90Y source. The dose rates measured with the plastic scintillator in the solid water phantom are in agreement with those directly measured in water. The measured relative dose distributions can be reproduced by Monte Carlo calculations. Also, the influence of the balloon diameter on the dose rate can be reproduced by the calculations. The dose rate calibration routinely performed with the plastic scintillator was checked for fifty-one sources with a well chamber and with another dedicated dose rate checking device. These measurements show that the consistency of the calibration of these sources was better than 10%. In a previous paper absolute dose rates for five other 90Y sources measured with TLD and radiochromic film in a solid water phantom were compared with those obtained with the plastic scintillator in water [Piessens and Reynaert, "Verification of absolute dose rates for intravascular beta sources," Phys. Med. Biol. 45, 2219-2231 (2000)]. Differences of 25 to 41%, depending on the balloon diameter, were reported. In this paper we show the evidence for three main reasons for these previously observed discrepancies: an inconsistency between a detector calibration performed with a 6 MeV electron beam and with a calibrated 90Sr/90Y source from NIST (16%), inaccuracies of the measuring distances in the solid water phantom (maximum 7.5%) and a time instability of the plastic scintillator, probably due to radiation damage (6%).

Absorbed dose to water based dosimetry versus air kerma based dosimetry for high-energy photon beams: an experimental study.

In recent years, a change has been proposed from air kerma based reference dosimetry to absorbed dose based reference dosimetry for all radiotherapy beams of ionizing radiation. In this paper, a dosimetry study is presented in which absorbed dose based dosimetry using recently developed formalisms was compared with air kerma based dosimetry using older formalisms. Three ionization chambers of each of three different types were calibrated in terms of absorbed dose to water and air kerma and sent to five hospitals. There, reference dosimetry with all the chambers was performed in a total of eight high-energy clinical photon beams. The selected chamber types were the NE2571, the PTW-30004 and the Wellhöfer-FC65G (previously Wellhöfer-IC70). Having a graphite wall, they exhibit a stable volume and the presence of an aluminium electrode ensures the robustness of these chambers. The data were analysed with the most important recommendations for clinical dosimetry: IAEA TRS-398, AAPM TG-51, IAEA TRS-277, NCS report-2 (presently recommended in Belgium) and AAPM TG-21. The necessary conversion factors were taken from those protocols, or calculated using the data in the different protocols if data for a chamber type are lacking. Polarity corrections were within 0.1% for all chambers in all beams. Recombination corrections were consistent with theoretical predictions, did not vary within a chamber type and only slightly between different chamber types. The maximum chamber-to-chamber variations of the dose obtained with the different formalisms within the same chamber type were between 0.2% and 0.6% for the NE2571, between 0.2% and 0.6% for the PTW-30004 and 0.1% and 0.3% for the Wellhöfer-FC65G for the different beams. The absorbed dose results for the NE2571 and Wellhöfer-FC65G chambers were in good agreement for all beams and all formalisms. The PTW-30004 chambers gave a small but systematically higher result compared to the result for the NE2571 chambers (on the average 0.1% for IAEA TRS-277, 0.3% for NCS report-2 and AAPM TG-21 and 0.4% for IAEA TRS-398 and AAPM TG-51). Within the air kerma based protocols, the results obtained with the TG-21 protocol were 0.4-0.8% higher mainly due to the differences in the data used. Both absorbed dose to water based formalisms resulted in consistent values within 0.3%. The change from old to new formalisms is discussed together with the traceability of calibration factors obtained at the primary absorbed dose and air kerma standards in the reference beams (60Co). For the particular situation in Belgium (calibrations at the Laboratory for Standard Dosimetry of Ghent) the change amounts to 0.1-0.6%. This is similar to the magnitude of the change determined in other countries.