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We describe the rationale and design of a double-blind, randomized, multicenter, dose-comparison study of interferon-beta-1a (IFN-β-1a; AVONEX[sup ®]), in the treatment of relapsing multiple sclerosis (MS). The study is expected to provide quantitative insights on the dose range for optimal clinical benefits in MS. The study involves 802 patients in 10 European countries who have EDSS scores 2.0 – 5.5, and who have experienced at least two relapses within the 3 years prior to enrolment. Patients are randomized to receive once-weekly intramuscular injections of IFN-β-1a 30 or 60 mcg for at least 3 years. The primary endpoint of the study is the effect of IFN-β-1a therapy on the time to sustained progression of disability. For patients with a baseline EDSS ⩽4.5, sustained progression of disability is defined as a 1 point increase in EDSS from baseline, maintained for 6 months. For patients with baseline EDSS ⩾5, sustained progression of disability is defined as reaching an EDSS ⩾6.0, maintained for 6 months. EDSS scores will be determined every 3 months. A series of prospectively defined secondary and tertiary efficacy endpoints will be examined. Safety will be monitored throughout the study. Magnetic resonance imaging (MRI) with and without gadolinium-enhancement has been performed in at least 358 patients at baseline and repeated annually after enrolment. In a subset of these patients, a frequent MRI study is also being performed. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate high-dose single fraction delivered with monochromatic X-rays minibeams for the radiotherapy of primary brain tumors in rats. Methods and Materials: Two groups of healthy rats were irradiated with one anteroposterior minibeam incidence (four minibeams, 123 Gy prescribed dose at 1 cm depth in the brain) or two interleaved incidences (54 Gy prescribed dose in a 5 × 5 × 4.8 mm3 volume centered in the right hemisphere), respectively. Magnetic resonance imaging (MRI) follow-up was performed over 1 year. T2-weighted (T2w) images, apparent diffusion coefficient (ADC), and blood vessel permeability maps were acquired. F98 tumor bearing rats were also irradiated with interleaved minibeams to achieve a homogeneous dose of 54 Gy delivered to an 8 × 8 × 7.8 mm3 volume centered on the tumor. Anatomic and functional MRI follow-up was performed every 10 days after irradiation. T2w images, ADC, and perfusion maps were acquired. Results: All healthy rats were euthanized 1 year after irradiation without any clinical alteration visible by simple examination. T2w and ADC measurements remain stable for the single incidence irradiation group. Localized Gd-DOTA permeability, however, was observed 9 months after irradiation for the interleaved incidences group. The survival time of irradiated glioma bearing rats was significantly longer than that of untreated animals (49 ± 12.5 days versus 23.3 ± 2 days, p < 0.001). The tumoral cerebral blood flow and blood volume tend to decrease after irradiation. Conclusions: This study demonstrates the sparing effect of minibeams on healthy tissue. The increased life span achieved for irradiated glioma bearing rats was similar to the one obtained with other radiotherapy techniques. This experimental tumor therapy study shows the feasibility of using X-ray minibeams with high doses in brain tumor radiotherapy. [ABSTRACT FROM AUTHOR]