Neuropathological postmortem evaluation of BNCT for GBM

Background - Thirty patients with glioblastoma multiforme (GBM) were treated by boron neutron capture therapy (BNCT) at the Studsvik facility in Sweden, in a clinical trial exploring a procedure in which 900 mg p-boronophenylalanine (BPA) per kilo body weight was infused in 6 h. Objective - The present study was designed to assess tumor efficacy and radiation damage to the brain for the seven patients in the Studsvik trial that were available for postmortem neuropathological examination. Method - Whole brain slices containing the initial tumor site and other regions showing pathological changes were chosen for microscopy and selected areas were studied by immunological methods. Results - Local control of GBM was observed in all cases. Conclusive evidence for radiation induced brain damage was not found. Conclusion - Using a novel procedure for BPA infusion, BNCT achieves local control of GBM for minimum tumor doses as low as 15 wGy, allowing treatment with very low concomitant doses to surrounding healthy tissues

An investigation of boron neutron capture therapy for recurrent glioblastoma multiforme

Objectives – To explore the use of boron neutron capture therapy (BNCT) for patients with glioblastoma multiforme (GBM), recurring after surgery and conventional radiotherapy (photon radiotherapy). Materials and methods – Boron uptake in recurrent GBM was measured for four patients. Twelve patients were subsequently treated by BNCT with boronophenylalanine-fructose (900 mg⁄kg body weight), administered by intravenous infusion for 6 h. Results – Median survival time from initial diagnosis was 22.2 months. Comparison with other BNCT studies indicates a clinical advantage of the prolonged infusion. BNCT was well tolerated and quality of life remained stable until tumor progression for all 12 patients. No correlation was found between survival times and minimum tumor dose and number of radiation fields. Conclusions – Boron neutron capture therapy, with the prolonged procedure for infusion, is at least as effective as other radiation therapies for recurrent GBM and is delivered in one treatment session, with low radiation dose to the healthy brain. Survival from diagnosis compares favorably with that obtained with conventional radiotherapy plus concomitant and adjuvant temozolomide (TMZ) and survival from recurrence compares favorably with that obtained with TMZ at first relapse. The results of the present investigation are encouraging and should be confirmed in a randomized trial

Boron neutron capture therapy for glioblastoma multiforme: advantage of prolonged infusion of BPA-f

Objectives – To assess possible improved efficacy of Boron Neutron Capture Therapy (BNCT) for glioblastoma multiforme (GBM) using prolonged infusion and a correspondingly higher dose of l-boronophenylalanine, as the fructose complex (BPA-f). Materials and methods – The benefit of prolonged infusion was analyzed by comparing the results from a Phase II study using 6 h infusion of BPA-f with those obtained from a Phase I ⁄ II study using 2 h of infusion. Median survival time (MST) from diagnosis, patient baseline characteristics, salvage treatment and severe adverse events were considered in the comparison. Results – MST increased significantly, from 12.8 (95% confidence interval or CI: 10.3–14.0) months with 2 h infusion to 17.7 (95% CI: 13.6–19.9) months with 6 h of infusion. The fraction of patients with WHO grade 3–4 adverse events was similar in the two studies at 13% and 14%, respectively. Conclusion – Prolonged infusion was found to be beneficial for the efficacy of BNCT and it is suggested that 6 h infusion of BPA-f should be used in future trials of BNCT for GBM. BNCT, which is a single-day treatment with mild side effects, should be assessed in a controlled trial, as an alternative to 30 daily fractions of conventional fractionated photon therapy over a period of 6 weeks