Postoperative treatment of glioblastoma with BNCT at the Petten irradiation facility (EORTC Protocol 11961)

Abstract

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.

The Anionic Boron Cluster (B12H11SH)2− as a Means To Trigger Release of Liposome Contents

“…[7] Repeated administration is possible and leads to higher blood concentration. [8] BSH triggers release of liposome content in a dose-dependent manner. Concentrations of 1 mm BSH are sufficient to noticeably increase the release rate of carboxyfluorescein (CF) encapsulated in liposomes prepared from DPPC, either alone or supplemented with 2 mol % 1,2-disteaoryl-sn-glycero-3-phosphatidyl-ethanolamine-N-[methoxypoly(ethylene glycol)] (DSPE-PEG2000) (see Figure 1).…”

A Review of Current and Future Treatment Strategies for Malignant Astrocytomas in Adults

“…Currently, newly developed radiosensitizers, e. g. Gadolinium-Texaphyrin and RSR13 (an allosteric effector of hemoglobin), and boron neutron capture therapy [29] are under investigation. Experimental studies measuring the regrowth delay of in vitro or in vivo irradiated human malignant glioma cells suggest that continuous ultra-low dose-rate irradiation increases the effect of fractionated high-dose-rate treatment [80].…”

Neutron Activation of Patients Following Boron Neutron Capture Therapy of Brain Tumors at the High Flux Reactor (HFR) Petten (EORTC Trials 11961 and 11011)

“…In EORTC trial 11961 (BNCT treatment of glioblastoma multiforme, with BSH) [6,7,20], each patient received four fractions (apart from the very first patient in whom, due to complications, the treatment had to be completed on the 3rd day giving an increased dose at the third fraction). The first five patients were treated with one beam, all others with the application of two beams.…”

“…The first European clinical trial on BNCT, a phase I trial (EORTC protocol 11961) for patients suffering from glioblastoma multiforme, started at Petten in October 1997 [6,7,20]. Glioblastoma was selected due to its poor prognosis, which has not really changed over the last decades [5,11,15,23].…”