BSH proved to be safe for clinical application at a dose of 100 mg BSH/kg infused and at a dose rate of 1 mg/kg/min. The study underlines the importance of a further investigation of BSH uptake in order to obtain enough data for significant statistical analysis. The boron concentration in blood seems to be a quite reliable parameter to predict the boron concentration in other tissues.

The boron neutron capture therapy is based on the reaction occurring between the isotope 10B and thermal neutrons. A low energy neutron is captured by the nucleus and it disintegrates into two densely ionising particles, Li nucleus and He nucleus (alpha particle), with high biological effectiveness. On the basis of comprehensive preclinical investigations in the frame of the European Collaboration with Na2B12H11SH (BSH), as boron delivery agent, the first European phase I, clinical trial was designed at the only available epithermal beam in Europe, at the High Flux Reactor, Petten, in the Netherlands. The goal of this study is to establish the safe BNCT dose for cranial tumors under defined conditions. BNCT is applied as postoperative radiotherapy in 4 fractions, after removal of the tumor for a group of patients suffering from glioblastoma, who would have no benefit from conventional treatment, but have sufficient life expectancy to detect late radiation morbidity due to BNCT. The starting dose is set at 80% of the dose where neurological effects occurred in preclinical large animal experiments following a single fraction. The radiation dose will be escalated, by constant boron concentration in blood, in 4 steps for cohorts of ten patients, after an observation period of at least 6 months after the end of BNCT of the last patient of a cohort. The adverse events on healthy tissues due to BSH and due to the radiotherapy will be analysed in order to establish the maximal tolerated dose and dose limiting toxicity. Besides of the primary aim of this study the survival will be recorded. The first patient was treated in October 1997, and further four patients have been irradiated to-date. The protocol design proved to be well applicable, establishing the basis for scientific evaluation, for performance of safe patient treatment in a very complex situation and for opening the possibility to perform further clinical research work on BNCT.

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Small compact-tension (½TCT) specimens of Type 304 and Type 316 stainless steels have been irradiated to a relatively low fluence level of 2 × 1024 neutrons (n)/m2 (E > 0.1 MeV) at a fast to thermal fluence ratio of about 1 at 823 K. Comparative constant-load-amplitude fatigue tests (aimed to link the reported data from earlier tests on high-fluence irradiated, single-edge-notch-cantilever (SENC) specimens of Type 316 and tests on low-fluence irradiated compact-tension (CT) specimens ( (V = 50 mm) of Type 304) have been performed in air with cyclic frequencies ranging from 10 Hz to 0.01 Hz at 823 K and 853 K. The trends of the crack growth curves were in good correspondence with the results from previous tests at the Naval Research Laboratory (NRL) and at the Netherlands Energy Research Foundation (ECN). The effect of the irradiation on the fatigue behavior under high-frequency loading was minor. However, the crack growth rate was significantly increased under low-frequency loading due to enhanced intergranular crack formation. Detailed comparison of present results with previous NRL data for high-fluence irradiated Type 316 showed that the fatigue crack growth rate is more affected by the low-fluence irradiation due to helium-enhanced intergranular crack growth. It is concluded that effects of testing procedures and specimen geometry are minor compared to the effects of irradiation on the fatigue crack growth rate at low cyclic frequencies.

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