Translational Boron Neutron Capture Therapy (BNCT) studies performed by our group and clinical BNCT studies worldwide have shown the therapeutic efficacy of BNCT for head and neck cancer. The present BNCT studies in veterinary patients with head and neck cancer were performed to optimize the therapeutic efficacy of BNCT, contribute towards exploring the role of BNCT in veterinary medicine, put in place technical aspects for an upcoming clinical trial of BNCT for head and neck cancer at the RA-6 Nuclear Reactor, and assess the feasibility of employing the existing B2 beam to treat large, deep-seated tumors. Five dogs with head and neck cancer with no other therapeutic option were treated with two applications of BNCT mediated by boronophenyl-alanine (BPA) separated by 3–5 weeks. Two to three portals per BNCT application were used to achieve a potentially therapeutic dose over the tumor without exceeding normal tissue tolerance. Clinical and Computed Tomography results evidenced partial tumor control in all cases, with slight-moderate mucositis, excellent life quality, and prolongation in the survival time estimated at recruitment. These exploratory studies show the potential value of BNCT in veterinary medicine and contribute towards initiating a clinical BNCT trial for head and neck cancer at the RA-6 clinical facility.

Objective. Boron Neutron Capture Therapy is a cancer radiotherapy that uses the selective uptake of boron compounds by tumor cells, followed by neutron irradiation. Conventional dosimetry generally assumes a homogeneous boron distribution within tissues, yet evidence indicates intracellular heterogeneity. This work aims to improve the Photon Isoeffective Dose model (PID) for Glioblastoma Multiforme (GBM) by incorporating subcellular-scale effects: (i) a correction factor for the stochastic nature of energy deposition due to intracellular boron localization, and (ii) the treatment of the nucleus-to-cytoplasm boron concentration ratio as a stochastic variable. Approach. The boron-10 microdistribution in U-87 glioblastoma cells was quantified for the first time through neutron autoradiography, revealing preferential accumulation in the nucleus. Following these experimental data, the nucleus-to-cytoplasm boron concentration ratio was described by a lognormal random variable, consistent with biological uptake processes. The correction factor was applied to the dosimetry of U-87 radiobiological data. Then, updated radiobiological parameters and subcellular-scale effects were integrated into the PID formalism and applied to a clinical case of GBM. Main results. The outcome was a Microdosimetric Photon Isoeffective Dose Model, which extends conventional PID by explicitly including intracellular boron heterogeneity. Applied to U-87 data, proposed corrections revealed a 47% reduction in the Compound Biological Effectiveness factor compared to conventional calculations, showing that neglecting subcellular distribution substantially overestimates the boron dose. For the clinical case, the total dose and 1-year Progression-Free Survival (PFS) differed only by 4% and 3%, respectively, compared to conventional dosimetry. However, perturbation analyses indicated that under higher intracellular heterogeneity, plausible in vivo, the deviations could become substantial (up to 22% in dose and 68% in PFS). Significance. These findings highlight the relevance of subcellular-scale modeling. The proposed Microdosimetric Model, grounded on experimentally derived microdosimetric corrections, provides a robust framework to improve both the accuracy and the personalization of BNCT treatment planning.

Background: Boron neutron capture therapy (BNCT) is a binary modality based on the nuclear reaction ¹⁰B (n, α) lithium-7 (⁷Li) that has been used to treat a variety of tumors, among these, cutaneous melanoma (CM). In previous boron biodistribution studies in agreement with the personalized oncology, we have demonstrated that boronophenylalanine (BPA) uptake can be correlated with the tumoral temperature and viability. The main aim of these studies was to evaluate the relationship between tumoral temperature and the response to the complete BNCT. Methods: Nude mice were implanted with human melanoma cells (Mel J) and divided into different groups (Control, NCT, BNCT I and BNCT II) and irradiated with the thermal neutron beam from RA-6 (4.96×10⁸/cm²/sec) during 37 and 55 minutes respectively. Tumor and body temperatures were measured by Static Infrared Imaging (SIRI), and it was performed the following up of the animals. Results: Tumor growth showed a complete growth inhibition during the first 20 days after treatment in both BNCT groups (BNCT I and BNCT II vs. Control P<0.001). Considering the analogy between the Fourier’s Law of Heat Conduction and the Ohm’s law of Electrical Conduction, the quantity (T_tum-T_inf)/(T_body-T_tum) was analyzed as a function of Vf/Vi (Final volume/Initial volume) ratio. A tendency to higher values of the temperature’s ratios, was observed with respect to the degree of tumor control (BNCT I with a R² of 0.3527, BNCTII with a R² of 0.3327) in agreement with previous boron biodistribution studies. The histology and immunohistochemical studies showed larger areas of necrosis and picnotic regions and a significant decrease of the Ki-67 antibody labeling in the BNCT II group evidencing important tumor damage. Conclusions: tumoral characteristics, especially the temperature, could be used to plan a personalized treatment for each patient. As values of correlation between temperature and tumoral response showed to be weak, we considered to explore a new model of three dimension for heat transport process.