An Integrated Monte Carlo Model for Heterogeneous Glioblastoma Treated with Boron Neutron Capture Therapy

SIMPLE SUMMARY: Glioblastoma (GBM) is the most aggressive type of astrocytic glioma. GBMs are diffuse infiltrating tumours that present with extensive hypoxia and genetic heterogeneity amongst other features that have rendered treatment strategies ineffectual, despite recent advances in multimodality therapy regimens. The prognosis remains poor and median survival is less than 17 months using adjuvant chemotherapy and X-ray external radiotherapy. Therefore, strategies should be investigated to target complications associated with this malignancy. A targeted approach with high linear energy transfer particles could address infiltration and cellular aggressiveness (e.g., heterogeneity, hypoxia, and intrinsic radiosensitivity) issues, respectively. Boron neutron capture therapy (BNCT), a biochemically-targeted modality, proposes an attractive solution for GBM. A hybrid computational framework was previously developed by our group to quantify the efficacy of BNCT at its current status of development for a simplified GBM model. This work has expanded the framework to a semi-realistic GBM model with heterogeneous radiosensitivity and anisotropic microscopic extensions; moreover, the neutron beam model and neutron transport components have undergone substantial improvements. ABSTRACT: Background: Glioblastomas (GBMs) are notorious for their aggressive features, e.g., intrinsic radioresistance, extensive heterogeneity, hypoxia, and highly infiltrative behaviours. The prognosis has remained poor despite recent advances in systemic and modern X-ray radiotherapy. Boron neutron capture therapy (BNCT) represents an alternative radiotherapy technique for GBM. Previously, a Geant4 BNCT modelling framework was developed for a simplified model of GBM. Purpose: The current work expands on the previous model by applying a more realistic in silico GBM model with heterogeneous radiosensitivity and anisotropic microscopic extensions (ME). Methods: Each cell within the GBM model was assigned an [Formula: see text] value associated with different GBM cell lines and a [Formula: see text] B concentration. Dosimetry matrices corresponding to various MEs were calculated and combined to evaluate cell survival fractions (SF) using clinical target volume (CTV) margins of 2.0 & 2.5 cm. SFs for the BNCT simulation were compared with external X-ray radiotherapy (EBRT) SFs. Results: The SFs within the beam region decreased by more than two times compared to EBRT. It was demonstrated that BNCT results in markedly reduced SFs for both CTV margins compared to EBRT. However, the SF reduction as a result of the CTV margin extension using BNCT was significantly lower than using X-ray EBRT for one MEP distribution, while it remained similar for the other two MEP models. Conclusions: Although the efficiency of BNCT in terms of cell kill is superior to EBRT, the extension of the CTV margin by 0.5 cm may not increase the BNCT treatment outcome significantly.