Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Dosimetric study of a new polymer encapsulated palladium-103 seed.

The use of low-energy photon emitters for brachytherapy applications, as in the treatment of prostate or ocular tumours, has increased significantly over the last few years. Several new seed models utilizing 103Pd and 125I have recently been introduced. Following the TG43U1 recommendations of the AAPM (American Association of Physicists in Medicine) (Rivard et al 2004 Med. Phys. 31 633), dose distributions around these low-energy photon emitters are characterized by the dose rate constant, the radial dose function and the anisotropy function in water. These functions and constants can be measured for each new seed in a solid phantom (i.e. solid water such as WT1) using high spatial resolution detectors such as very small thermoluminescent detectors. These experimental results in solid water must then be converted into liquid water by using Monte Carlo simulations. This paper presents the dosimetric parameters of a new palladium seed, OptiSeed (produced by International Brachytherapy (IBt), Seneffe, Belgium), made with a biocompatible polymeric shell and with a design that differs from the hollow titanium encapsulated seed, InterSource103, produced by the same company. A polymer encapsulation was chosen by the company IBt in order to reduce the quantity of radioactive material needed for a given dose rate, and to improve the symmetry of the radiation field around the seed. The necessary experimental data were obtained by measurements with LiF thermoluminescent dosimeters (1 mm3) in a solid water phantom (WT1) and then converted to values in liquid water using Monte Carlo calculations (MCNP-4C). Comparison of the results with a previous study by Reniers et al (2002 Appl. Radiat. Isot. 57 805) shows very good agreement for the dose rate constant and for the radial dose function. In addition, the results also indicate an improvement in isotropy compared to a conventional titanium encapsulated seed. The relative dose (anisotropy value relative to 90 degrees ) from the seed at a distance of 3 cm is close to 70% at 0 degrees whereas that for the titanium encapsulated InterSource103seed is close to 40%. This paper also presents some new Monte Carlo calculations relating to shadowing produced by the seeds in an array implanted for a prostate cancer treatment. Recently, Mobit and Badragan (2004 Phys. Med. Biol. 49 3171) reported shadowing resulting in a 10% decrease in dose from titanium encapsulated 125I seed. We used Monte Carlo simulations (MCNP-4C) to evaluate shadowing for the InterSource103 titanium encapsulated seed and the OptiSeed polymer encapsulated seed. For a specific geometry specified, dose decreases of 13% and 7% were found for the InterSource103 titanium encapsulated and the OptiSeed polymer encapsulated seed, respectively

Analytical model of the binary multileaf collimator of tomotherapy for Monte Carlo simulations

Helical tomotherapy (HT) delivers intensity-modulated radiotherapy by the means of many configurations of the binary multi-leaf collimator (MLC). The aim of the present study was to devise a method, which we call the "transfer function" (TF) method, to perform the transport of particles through the MLC much faster than the time consuming Monte Carlo (MC) simulation and with no significant loss of accuracy. The TF method consists of calculating, for each photon in the phase-space file, the attenuation factor for each leaf (up to three) that the photon passes, assuming straight propagation through closed leaves, and storing these factors in a modified phase-space file. To account for the transport through the MLC in a given configuration, the weight of a photon is simply multiplied by the attenuation factors of the leaves that are intersected by the photon ray and are closed. The TF method was combined with the PENELOPE MC code, and validated with measurements for the three static field sizes available (40x5, 40x2.5 and 40x1 cm 2) and for some MLC patterns. The TF method allows a large reduction in computation time, without introducing appreciable deviations from the result of full MC simulations

Calculation of beta-ray dose distributions from ophthalmic applicators and comparison with measurements in a model eye

Dose distributions throughout the eye, from three types of beta-ray ophthalmic applicators, were calculated using the EGS4, ACCEPT 3.0, and other Monte Carlo codes. The applicators were those for which doses were measured in a recent international intercomparison [Med. Phys. 28, 1373 (2001)], planar applicators of Ru-106-Rh-106 and Sr-90-Y-90 and a concave Ru-106-Rh-106 applicator. The main purpose was to compare the results of the various codes with average experimental values. For the planar applicators, calculated and measured doses on the source axis agreed within the experimental errors (<10%) to a depth of 7 mm for Ru-106-Rh-106 and 5 mm for Sr-90-Y-90. At greater distances the measured values are larger than those calculated. For the concave Ru-106-Rh-106 applicator, there was poor agreement among available calculations and only those calculated by ACCEPT 3.0 agreed with measured values. In the past, attempts have been made to derive such dose distributions simply, by integrating the appropriate point-source dose function over the source, Here, we investigated the accuracy of this procedure for encapsulated sources, by comparing such results with values calculated by Monte Carlo, An attempt was made to allow for the effects of the silver source window but no corrections were made for scattering from the source backing. In these circumstances, at 6 mm depth, the difference in the results of the two calculations was 14%-18% for a planar Ru-106-Rh-106 applicator and up to 30% for the concave applicator. It becomes worse at greater depths. These errors are probably caused mainly by differences between the spectrum of beta particles transmitted by the silver window and those transmitted by a thickness of water having the same attenuation properties. (C) 2001 American Association of Physicists in Medicine