BORON NEUTRON-CAPTURE THERAPY (BNCT) FOR GLIOBLASTOMA-MULTIFORME (GBM) USING THE EPITHERMAL NEUTRON BEAM AT THE BROOKHAVEN-NATIONAL-LABORATORY

Objective: Boron neutron-capture therapy (BNCT) is a binary form of ra diation therapy based on the nuclear reactions that occur when boron ( B-10) is exposed to thermal neutrons. Preclinical studies have demonst rated the therapeutic efficacy of p-boronophenylalanine (EPA)-based BN CT. The objectives of the Phase I/II trial were to study the feasibili ty and safety of single-fraction BNCT in patients with GEM. Materials and Methods: The trial design required (a) a BPA biodistribution study performed at the time of craniotomy; and (b) BNCT within approximate to 4 weeks of the biodistribution study. From September 1993 to July 1 995, 10 patients were treated. For biodistribution, patients received a 2-hour intravenous (i.v.) infusion of BPA-fructose complex (BPA-F). Blood samples, taken during and after infusion, and multiple tissue sa mples collected during surgical debulking were analyzed for B-10 conce ntration. For BNCT, all patients received a dose of 250 mg BPA/kg admi nistered by a 2-hour i.v. infusion of BPA-F, followed by neutron beam irradiation at the Brookhaven Medical Research Reactor (BMRR). The ave rage blood B-10 concentrations measured before and during treatment me re used to calculate the time of reactor irradiation that would delive r the prescribed dose. Results: B-10 concentrations in specimens of sc alp and tumor were higher than in blood by factors of approximate to 1 .5 and approximate to 3.5, respectively. The B-10 concentration in the normal brain was less than or equal to that in the blood; however, fo r purposes of estimating radiation doses to normal brain endothelium, it was always assumed to be equal to blood. BNCT doses are expressed a s gray-equivalent (Gy-Eq), which is the sum of the various physical do se components multiplied to appropriate biologic effectiveness factors . The dose to a 1-cm(3) volume where the thermal flux reached a maximu m was 10.6 +/- 0.3 Gy-Eq in 9 patients and 13.8 Gy-Eq in 1 patient. Th e minimum dose in tumor ranged from 20 to 32.3 Gy-Eq. The minimum dose in the target volume (tumor plus 2 cm margin) ranged from 7.8 to 16.2 Gy-Eq. Dose to scalp ranged from 10 to 16 Gy-Eq. All patients experie nced in-field alopecia. No CNS toxicity attributed to BNCT was observe d. The median time to local disease progression following BNCT was 6 m onths (range 2.7 to 9.0). The median time to local disease progression was longer in patients who received a higher tumor dose. The median s urvival time from diagnosis was 13.5 months. Conclusion: It is feasibl e to safely deliver a single fraction of BPA-based BNCT. At the dose p rescribed, the patients did not experience any morbidity. To further e valuate the therapeutic efficacy of BNCT, a dose-escalation study deli vering a minimum target volume dose of 17 Gy-Eq is in progress. (C) 19 98 Elsevier Science Inc.