Experimental studies for the personalized application of boron neutron capture therapy to the treatment of cutaneous melanoma

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.Fil: Carpano, Marina. Comisión Nacional de Energía Atómica; ArgentinaFil: Santa Cruz, Gustavo Alberto. Comisión Nacional de Energía Atómica; ArgentinaFil: Rodriguez, Carla. Comisión Nacional de Energía Atómica; ArgentinaFil: Nievas, Susana Isabel. Comisión Nacional de Energía Atómica; ArgentinaFil: Olivera, María Silvina. Comisión Nacional de Energía Atómica; ArgentinaFil: Perona, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Boggio, Esteban Fabián. Comisión Nacional de Energía Atómica; ArgentinaFil: Longhino, Juan Manuel. Comisión Nacional de Energía Atómica; ArgentinaFil: Pisarev, Mario Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Juvenal, Guillermo Juan. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Dagrosa, María Alejandra. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Clinical veterinary boron neutron capture therapy (BNCT) studies in dogs with head and neck cancer: Bridging the gap between translational and clinical studies

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.Fil: Schwint, Amanda Elena. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Monti Hughes, Andrea. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Garabalino, Marcela Alejandra. Comisión Nacional de Energía Atómica; ArgentinaFil: Santa Cruz, Gustavo Alberto. Comisión Nacional de Energía Atómica; ArgentinaFil: González, Sara Josefina. Comisión Nacional de Energía Atómica. Gerencia del Área de Investigación y Aplicaciones No Nucleares. Gerencia Física (Centro Atómico Constituyentes). Proyecto Tandar; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Longhino, Juan Manuel. Comisión Nacional de Energía Atómica; ArgentinaFil: Provenzano, Lucas. Comisión Nacional de Energía Atómica. Gerencia del Área de Investigación y Aplicaciones No Nucleares. Gerencia Física (Centro Atómico Constituyentes). Proyecto Tandar; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Oña, Paulina. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Instituto de Tecnologías Nucleares para la Salud; ArgentinaFil: Rao, Monica. Hospital Veterinario; ArgentinaFil: Cantarelli, María de los Ángeles. Hospital Veterinario; ArgentinaFil: Leiras, Andrea. No especifíca;Fil: Olivera, María Silvina. Comisión Nacional de Energía Atómica; ArgentinaFil: Trivillin, Verónica Andrea. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Alessandrini, Paula. No especifíca;Fil: Brollo, Fabricio Raul. Comisión Nacional de Energía Atómica; ArgentinaFil: Boggio, Esteban Fabián. Comisión Nacional de Energía Atómica; ArgentinaFil: Costa, Hernan. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Instituto de Tecnologías Nucleares para la Salud; ArgentinaFil: Ventimiglia, Romina. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Instituto de Tecnologías Nucleares para la Salud; ArgentinaFil: Binia, Sergio. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Instituto de Tecnologías Nucleares para la Salud; ArgentinaFil: Pozzi, Emiliano César Cayetano. Comisión Nacional de Energía Atómica; ArgentinaFil: Nievas, Susana Isabel. Comisión Nacional de Energía Atómica; ArgentinaFil: Santa Cruz, Iara S.. Comisión Nacional de Energía Atómica; Argentin

The essential role of radiobiological figures of merit for the assessment and comparison of beam performances in boron neutron capture therapy

Purpose: Boron Neutron Capture Therapy (BNCT) is a treatment modality that uses an external neutron beam to selectively inactive boron10-loaded tumor cells. This work presents the development and innovative use of radiobiological probability models to adequately evaluate and compare the therapeutic potential and versatility of beams presenting different neutron energy spectra. M&M: Aforementioned characteristics, collectively refer to as the performance of a beam, were defined on the basis of radiobiological probability models for the first time in BNCT. A model of uncomplicated tumor control probability (UTCP) for HN cancer was introduced. This model considers a NTCP able to predict severe mucositis and a TCP for non-uniform doses derived herein. A systematic study comprising a simplified HN cancer model is presented as a practical application of the introduced radiobiological figures of merit (FOM) for assessing and comparing the performance of different clinical beams. Applications involving treated HN cancer patients were also analyzed. Results: The maximum UTCP proved suitable and sensitive to assess the performance of a beam, revealing particularities of the studied sources that the physical FOMs do not highlight. The radiobiological FOMs evaluated in patients showed to be useful tools both for retrospective analysis of the BNCT treatments, and for prospective studies of beam optimization and feasibility. Conclusions: The presented developments and applications demonstrated that it is possible to assess and compare performances of completely different beams fairly and adequately by assessing the radiobiological FOM UTCP. Thus, this figure would be a practical and essential aid to guide treatment decisions.Fil: Provenzano, Lucas. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Koivunoro, H.. No especifíca;Fil: Postuma, I.. Istituto Nazionale di Fisica Nucleare; ItaliaFil: Longhino, Juan Manuel. Comisión Nacional de Energía Atómica; ArgentinaFil: Boggio, Esteban Fabián. Comisión Nacional de Energía Atómica; ArgentinaFil: Farías, R. O.. Universidad Favaloro; ArgentinaFil: Bortolussi, Silva. Istituto Nazionale di Fisica Nucleare; Italia. Universita degli Studi di Pavia; ItaliaFil: González, Sara Josefina. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin