We have applied boron neutron capture therapy (BNCT) to malignant brain tumors. Here we evaluated the survival benefit of BNCT for recurrent malignant glioma (MG). Since 2002, we have treated 22 cases of recurrent MG with BNCT. Survival time was analyzed with special reference to recursive partitioning analysis (RPA) classification, by Carson et al. (J Clin Oncol 25:2601-2606, 2007). Median survival times (MSTs) after BNCT for all patients and for glioblastoma as on-study histology at recurrence was 10.8 months (n = 22; 95% CI, 7.3-12.8 months) and 9.6 months (n = 19; 95% CI, 6.9-11.4 months), respectively. In our study, MST for the high-risk RPA classes was 9.1 months (n = 11; 95% CI, 4.4-11.0 months). By contrast, the original journal data showed that the MST of the same RPA classes was 4.4 months (n = 129; 95% CI, 3.6-5.4 months). BNCT showed a survival benefit for recurrent MG, especially in the high-risk group.

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Our concept of boron neutron capture therapy (BNCT) is selective destruction of tumor cells using the heavy-charged particles yielded through 10B(n, alpha)7 Li reactions. To design a new protocol that employs epithermal neutron beams in the treatment of glioma patients, we examined the relationship between the radiation dose, histological tumor grade, and clinical outcome. Since 1968, 183 patients with different kinds of brain tumors were treated by BNCT; for this retrospective study, we selected 105 patients with glial tumors who were treated in Japan between 1978 and 1997. In the analysis of side effects due to radiation, we included all the 159 patients treated between 1977 and 2001. With respect to the radiation dose (i.e. physical dose of boron n-alpha reaction), the new protocol prescribes a minimum tumor volume dose of 15 Gy or, alternatively, a minimum target volume dose of 18 Gy. The maximum vascular dose should not exceed 15 Gy (physical dose of boron n-alpha reaction) and the total amount of gamma rays should remain below 10 Gy, including core gamma rays from the reactor and capture gamma in brain tissue. The outcomes for 10 patients who were treated by the new protocol using a new mode composed of thermal and epithermal neutrons are reported.

We here propose a new model for estimating the biological effectiveness for boron neutron capture therapy (BNCT) considering intra- and intercellular heterogeneity in 10B distribution. The new model was developed from our previously established stochastic microdosimetric kinetic model that determines the surviving fraction of cells irradiated with any radiations. In the model, the probability density of the absorbed doses in microscopic scales is the fundamental physical index for characterizing the radiation fields. A new computational method was established to determine the probability density for application to BNCT using the Particle and Heavy Ion Transport code System PHITS. The parameters used in the model were determined from the measured surviving fraction of tumor cells administrated with two kinds of 10B compounds. The model quantitatively highlighted the indispensable need to consider the synergetic effect and the dose dependence of the biological effectiveness in the estimate of the therapeutic effect of BNCT. The model can predict the biological effectiveness of newly developed 10B compounds based on their intra- and intercellular distributions, and thus, it can play important roles not only in treatment planning but also in drug discovery research for future BNCT.

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TF-PEG-BSH is a potent BDS for BNCT not only in terms of delivering a high concentration of (10)B into tumor tissue, but also the selective delivery of (10)B into the tumor cells.

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The microdosimetric kinetic model (MKM) is widely used for estimating relative biological effectiveness (RBE)-weighted doses for various radiotherapies because it can determine the surviving fraction of irradiated cells based on only the lineal energy distribution, and it is independent of the radiation type and ion species. However, the applicability of the method to proton therapy has not yet been investigated thoroughly. In this study, we validated the RBE-weighted dose calculated by the MKM in tandem with the Monte Carlo code PHITS for proton therapy by considering the complete simulation geometry of the clinical proton beam line. The physical dose, lineal energy distribution, and RBE-weighted dose for a 155 MeV mono-energetic and spread-out Bragg peak (SOBP) beam of 60 mm width were evaluated. In estimating the physical dose, the calculated depth dose distribution by irradiating the mono-energetic beam using PHITS was consistent with the data measured by a diode detector. A maximum difference of 3.1% in the depth distribution was observed for the SOBP beam. In the RBE-weighted dose validation, the calculated lineal energy distributions generally agreed well with the published measurement data. The calculated and measured RBE-weighted doses were in excellent agreement, except at the Bragg peak region of the mono-energetic beam, where the calculation overestimated the measured data by ~15%. This research has provided a computational microdosimetric approach based on a combination of PHITS and MKM for typical clinical proton beams. The developed RBE-estimator function has potential application in the treatment planning system for various radiotherapies.