Radiosurgery (RS) treatment times vary, even for the same prescription dose, due to variations in the collimator size, the number of iso-centres/beams/arcs used and the time gap between each of these exposures. The biologically effective dose (BED) concept, incorporating fast and slow components of repair, was used to show the likely influence of these variables for Gamma Knife patients with Vestibular Schwannomas. Two patients plans were selected, treated with the Model B Gamma Knife, these representing the widest range of treatment variables; iso-centre numbers 3 and 13, overall treatment times 25.4 and 129.6 min, prescription dose 14 Gy. These were compared with 3 cases treated with the Perfexion(®) Gamma Knife. The iso-centre number varied between 11 and 18, treatment time 35.7 - 74.4 min, prescription dose 13 Gy. In the longer Model B Gamma Knife treatment plan the 14 Gy iso-dose was best matched by the 58 Gy2.47 iso-BED line, although higher and lower BED values were associated with regions on the prescription iso-dose. The equivalent value for the shorter treatment was 85 Gy2.47. BED volume histograms showed that a BED of 85 Gy2.47 only covered ∼65% of the target in the plan with the longer overall treatment time. The corresponding BED values for the 3 cases, treated with the Perfexion(®) Gamma Knife, were 59.5, 68.5 and 71.5 Gy2.47. In conclusion BED calculations, taking account of the repair of sublethal damage, may indicate the importance of reporting overall time to reflect the biological effectiveness of the total physical dose applied.

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.

Gamma Knife treatments are regarded as single dose exposures, however, in reality the total dose delivered is the addition of a variable number of individual smaller doses from the variable number of iso-centres or shots, selected to cover a lesion. The dose prescription, in terms of dose and dose rate, to different points on a given physical iso-surface, will vary according to location. In radiobiological terms this treatment pattern does not represent a single exposure, but a schedule with a variable number of different sized dose fractions given at different dose rates with multiple incompletes repair intervals (the time between shots). Using the concept of biologically effective dose (BED), incorporating a fast and a slow component of repair, the biological effectiveness of a 12-shot protocol was found to vary with the decay in the activity of the (60)Co sources and the time interval between shots. However, the largest effect was found when this standard protocol was compared with one involving only 2 shots. It should be recognised in individual Gamma Knife treatments that there are many variables which have the potential to influence the biological effective of the treatment and thus the importance of a single variable may be difficult to determine in isolation. Reports in the literature support the results of these simulated calculations into the factors likely to change the biologically effective dose with the use of the Gamma Knife.