Superiority of BNCT Treatment Planning Metrics Achieved Using Novel vs. Reference (BPA-F) Pharmaceuticals in Head and Neck Locations

Abstract

Several novel boron delivery compounds currently under investigation by our group have demonstrated formulation, biodistribution, and dose response benefits in small animal models [1]. In this study we analyze the potential clinical impact of these compounds for boron neutron capture therapy (BNCT) in human patients. Pharmacokinetic models were used to estimate the tumor and normal tissue boron concentrations after continuous infusion of the novel compounds and BPA-F. Patient model segmentation, material assignment, and alignment of one or more treatment beams were exported from a commercial treatment planning system (TPS) to a novel dose calculation tool. This information was used to generate a voxelized model that incorporated the source, beam shaping assembly, collimator, and patient materials so that the full albedo effect was included in each dose calculation. Physical dose from 10B(n,α), 14N(n,p), 1H(n,n') interactions plus gamma rays from 1H(n,γ) and other reactions within the patient and treatment equipment were calculated by Monte Carlo transport of particles originating in a pre-generated phase space at the cover surface. RBE and CBE weighting factors are applied to combine these four physical dose volumes into an equivalent dose volume, and these five dose volumes were passed back to the TPS for evaluation. Tumor dose was increased by up to 2.6x for the novel compounds while normal tissue doses were constant or slightly reduced in comparison to BPA-F plans. Alternatively, for identical tumor dose the normal tissue doses and treatment time were reduced by up to 2.6x. In addition, in some cases it was possible to generate a single beam treatment plan using the new compounds that delivered higher tumor dose and lower normal tissues doses than a multiple beam plan using BPA-F. This study demonstrates both dosimetric and practical benefits of the new compounds in comparison to BPA-F, including the potential to deliver treatment using fewer beam directions and correspondingly easier treatment setups and higher patient throughput. The potential of these compounds to extend the range of clinical indications for BNCT is also discussed. These results motivate upcoming experimental testing of the key assumptions involved in their calculation.