Postoperative treatment of glioblastoma with BNCT at the Petten Irradiation Facility (EORTC Protocol 11961)

The boron neutron capture therapy is based on the reaction occuring between the isotope B-10 and thermal neutrons. A low energy neutron is captured by the nucleus and it disintegrates into two densly ionising particles, Li nu cleus and He nucleus (alpha particle), with high biological effectiveness. On the basis of comprehensive preclinical investigations in the frame of th e European Collaboration with Na2B12H11SH (BSH), as boron delivery agent, t he first European phase I, clinical trial was designed at the only availabl e epithermal beam in Europe, at the High Flux Reactor, Petten, in the Nethe rland. The goal of this study is to establish the safe BNCT dose for crania l tumors under defined conditions. BNCT is applied as postoperative radioth erapy in 4 fractions; after removal of the tumor for a group of patients su ffering from glioblastoma, who would have no benefit from conventional trea tment, but have sufficient life expectancy to detect late radiation morbidi ty due to BNCT. The starting dose is set at 80% of the dose where neurological effects occu red in preclinical large animal experiments following a single fraction. Th e radiation dose will be escalated, by constant boron concentration in bloo d, in 4 steps for cohorts of ten patients, after an observation period of a t 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 radiotherap y will be analysed in order to establish the maximal tolerated dose and dos e limiting toxicity. Besides of the primary aim of this study the survival will be recorded. The first patient was treated in October 1997, and furthe r four patients have been irradiated todate. The protocol design proved to be well applicable, establishing the basis for scientific evaluation, for p erformance of safe patient treatment in a very complex situation and for op ening the possibility to perform further clinical research work on BNCT.