Boron neutron capture therapy for newly diagnosed glioblastoma multiforme: an assessment of clinical potential

Abstract

ABSTRACT. The purpose of this study was to assess the potential of boron neutron capture therapy (BNCT), with a 6-h infusion of the boron carrier L-boronophenylalanine as a fructose preparation (BPA-f), as first-line radiotherapy for newly diagnosed glioblastoma multiforme (GBM). Patient survival data from a Phase II study using BNCT were compared with retrospective data from the two arms of a Phase III study using conventional radiotherapy (RT) in the reference arm and using RT plus concomitant and adjuvant medication with temozolomide (TMZ) in the experimental arm, and were also compared with small subgroups of these patients for whom the methylation status of the MGMT (O 6 -methylguanine-DNA methyltransferase) DNA repair gene was known. Differences in the baseline characteristics, salvage therapy after recurrence and levels of severe adverse events were also considered. The results indicate that BNCT offers a treatment that is at least as effective as conventional RT alone. For patients with an unmethylated MGMT DNA repair gene, a possible clinical advantage of BNCT over RT/ TMZ was suggested. BNCT is a single-day treatment, which is of convenience to patients, with mild side effects, which would offer an initial 6 weeks of good-quality life during the time when patients would otherwise be undergoing daily treatments with RT and TMZ. It is suggested that the use of BNCT with a 6-h infusion of BPA-f should be explored in a stratified randomised Phase II trial in which patients with the unmethylated MGMT DNA repair gene are offered BNCT in the experimental arm and RT plus TMZ in the reference arm. Boron neutron capture therapy (BNCT) is an experimental radiotherapy that, to date, has mostly been applied to treating patients with newly diagnosed glioblastoma multiforme (GBM). Several hundred GBM patients have been treated in Phase I and Phase II studies in Europe, the USA and Japan, and survival times similar to those obtained with standard radiotherapy (RT) have been reported from several of these studies [1]. No randomised trial in which BNCT is compared with standard therapies has yet been undertaken.Proper assessment of the results from these Phase II trials has been hampered by the lack of information on baseline characteristics of the patient populations, both in reports of the BNCT studies and in reports on other therapies, notably standard fractionated photon therapy (RT), to which the results from BNCT should ultimately be compared. The recursive partitioning analysis (RPA) of prognostic factors by Curran et al [2] established a method to characterise patient status prior to treatment, useful both for the planning of clinical studies and for the assessment of the significance of the results from clinical studies. The reliability and usefulness of the RPA method has been verified by Mirimanoff et al [3] by applying it to data obtained from a randomised Phase III study [4], in which RT with concomitant and adjuvant temozolomide (RT/TMZ) was offered to 287 patients with newly diagnosed GBM in the experimen...

Glia to glioma: A wrathful journey

“…radiation therapies include Internal radiation Therapy, in which liquid radioactive materials are pumped into the surgically removed portion of the tumor through a small catheter to stop further growth of the existing tumor cells; external Beam radiation Therapy, where radioactive beams are passed penetrating the skull without any catheter to kill existing tumor cells left after surgery along with some normal tissue so that new cancerous transformation should be diminished; and Stereotactic radio Surgery, where scrupulously guided radioactive beams are zapped exactly on the lesion site without harming the peripheral normal tissues [131,132] . A new variation of this last one is the BoronNeutron Capture Therapy (BNCT) which has proven welldefined in treating glioma using the radioactive isotope of Boron [133][134][135] . However, above all the labor it takes to apply, side effects such as hair loss, body weakness and mutation of non-malignant tissue by radioactive hits dwarf down the efficacy of these radiotherapeutic applications.…”

Boron neutron capture therapy (BNCT) for newly-diagnosed glioblastoma: Comparison of clinical results obtained with BNCT and conventional treatment

“…In that trial the MST was 10.4-13.2 months for newly diagnosed GBM patients. In a Swedish clinical trial 29 newly diagnosed GBM patients received an infusion of 900 mg/kg BPA in the course of 6 hours (22)(23)(24)(25). The MST was 17.7 months compared to 15.5 months in patients who received standard therapy comprised of surgery followed by RT and TMZ.…”

From the laboratory to the clinic: How translational studies in animals have lead to clinical advances in boron neutron capture therapy

“…Based on the experimental data demonstrating a significant increase (P <0.05) in boron uptake in tumor cell clusters following a 6-hour vs a 2-hour i.v. infusion of BPA with a 90% increase in boron concentrations (65±11 vs 31±12 µg B/g tumor) (Smith et al, 2001), a Phase II clinical trial was initiated by a group in Studsvik, Sweden to evaluate a 6 hour infusion of BPA in patients with glioblastomas (Capala et al, 2003;Sköld et al, 2010). The Kaplan-Meier survival plots for these two groups are shown in Fig.…”