Clinical Veterinary Boron Neutron Capture Therapy (BNCT) Studies in Dogs with Head and Neck Cancer: Bridging the Gap Between Translational and Clinical Studies

Overview

Journal Biology (Basel)

Publisher MDPI

Specialty Biology

Date 2020 Oct 10

PMID 33036386

Citations 8

Authors

Amanda E Schwint

Andrea Monti Hughes

Marcela A Garabalino

Gustavo A Santa Cruz

Sara J Gonzalez

Juan Longhino

Lucas Provenzano

Paulina Ona

Monica Rao

Maria de Los Angeles Cantarelli

Andrea Leiras

Maria Silvina Olivera

Veronica A Trivillin

Paula Alessandrini

Fabricio Brollo

Esteban Boggio

Hernan Costa

Romina Ventimiglia

Sergio Binia

Emiliano C C Pozzi

Susana I Nievas

Iara S Santa Cruz

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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Cobaltabis(Dicarbollide) [-COSAN] for Boron Neutron Capture Therapy of Head and Neck Cancer: Biodistribution and Irradiation Studies in an Experimental Oral Cancer Model.

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Using the photon isoeffective dose formalism to compare and combine BNCT and CIRT in a head and neck tumour.

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Enhancement in the Therapeutic Efficacy of In Vivo BNCT Mediated by GB-10 with Electroporation in a Model of Oral Cancer.

Olaiz N, Monti Hughes A, Pozzi E, Thorp S, Curotto P, Trivillin V Cells. 2023; 12(9).

PMID: 37174642 PMC: 10177359. DOI: 10.3390/cells12091241.

References

Coderre J, Elowitz E, Chadha M, Bergland R, Capala J, JOEL D . Boron neutron capture therapy for glioblastoma multiforme using p-boronophenylalanine and epithermal neutrons: trial design and early clinical results. J Neurooncol. 1997; 33(1-2):141-52. DOI: 10.1023/a:1005741919442. View

Almela R, Anson A . A Review of Immunotherapeutic Strategies in Canine Malignant Melanoma. Vet Sci. 2019; 6(1). PMC: 6466282. DOI: 10.3390/vetsci6010015. View

Takeuchi A . Possible application of boron neutron capture therapy to canine osteosarcoma. Nihon Juigaku Zasshi. 1985; 47(6):869-78. DOI: 10.1292/jvms1939.47.869. View

Axiak-Bechtel S, Maitz C, Selting K, Bryan J . Preclinical imaging and treatment of cancer: the use of animal models beyond rodents. Q J Nucl Med Mol Imaging. 2015; 59(3):303-16. View

Kreimann E, Itoiz M, Longhino J, Blaumann H, Calzetta O, Schwint A . Boron neutron capture therapy for the treatment of oral cancer in the hamster cheek pouch model. Cancer Res. 2001; 61(24):8638-42. View

Dos Anjos D, Bueno C, Magalhaes L, Magalhaes G, Mattos-Junior E, Pinto M . Electrochemotherapy induces tumor regression and decreases the proliferative index in canine cutaneous squamous cell carcinoma. Sci Rep. 2019; 9(1):15819. PMC: 6825193. DOI: 10.1038/s41598-019-52461-6. View

Coderre J, Gavin P, Capala J, Ma R, Morris G, Button T . Tolerance of the normal canine brain to epithermal neutron irradiation in the presence of p-boronophenylalanine. J Neurooncol. 2000; 48(1):27-40. DOI: 10.1023/a:1006419210584. View

Monti Hughes A, Pozzi E, Thorp S, Curotto P, Medina V, Martinel Lamas D . Histamine reduces boron neutron capture therapy-induced mucositis in an oral precancer model. Oral Dis. 2015; 21(6):770-7. DOI: 10.1111/odi.12346. View

Kankaanranta L, Seppala T, Koivunoro H, Saarilahti K, Atula T, Collan J . Boron neutron capture therapy in the treatment of locally recurred head-and-neck cancer: final analysis of a phase I/II trial. Int J Radiat Oncol Biol Phys. 2011; 82(1):e67-75. DOI: 10.1016/j.ijrobp.2010.09.057. View

10.

Sonis S, Peterson R, Edwards L, Lucey C, Wang L, Mason L . Defining mechanisms of action of interleukin-11 on the progression of radiation-induced oral mucositis in hamsters. Oral Oncol. 2000; 36(4):373-81. DOI: 10.1016/s1368-8375(00)00012-9. View

11.

Menendez P, Roth B, Pereira M, Casal M, Gonzalez S, Feld D . BNCT for skin melanoma in extremities: updated Argentine clinical results. Appl Radiat Isot. 2009; 67(7-8 Suppl):S50-3. DOI: 10.1016/j.apradiso.2009.03.020. View

12.

Wang L, Liu Y, Chou F, Jiang S . Clinical trials for treating recurrent head and neck cancer with boron neutron capture therapy using the Tsing-Hua Open Pool Reactor. Cancer Commun (Lond). 2018; 38(1):37. PMC: 6006853. DOI: 10.1186/s40880-018-0295-y. View

13.

Wittig A, Sauerwein W, Coderre J . Mechanisms of transport of p-borono-phenylalanine through the cell membrane in vitro. Radiat Res. 2000; 153(2):173-80. DOI: 10.1667/0033-7587(2000)153[0173:motopb]2.0.co;2. View

14.

Monti Hughes A, Longhino J, Boggio E, Medina V, Martinel Lamas D, Garabalino M . Boron neutron capture therapy (BNCT) translational studies in the hamster cheek pouch model of oral cancer at the new "B2" configuration of the RA-6 nuclear reactor. Radiat Environ Biophys. 2017; 56(4):377-387. DOI: 10.1007/s00411-017-0710-9. View

15.

Kato I, Fujita Y, Maruhashi A, Kumada H, Ohmae M, Kirihata M . Effectiveness of boron neutron capture therapy for recurrent head and neck malignancies. Appl Radiat Isot. 2009; 67(7-8 Suppl):S37-42. DOI: 10.1016/j.apradiso.2009.03.103. View

16.

Molinari A, Pozzi E, Monti Hughes A, Heber E, Garabalino M, Thorp S . "Sequential" boron neutron capture therapy (BNCT): a novel approach to BNCT for the treatment of oral cancer in the hamster cheek pouch model. Radiat Res. 2011; 175(4):463-72. DOI: 10.1667/RR2148.1. View

17.

Bronson R . Variation in age at death of dogs of different sexes and breeds. Am J Vet Res. 1982; 43(11):2057-9. View

18.

Pozzi E, Cardoso J, Colombo L, Thorp S, Monti Hughes A, Molinari A . Boron neutron capture therapy (BNCT) for liver metastasis: therapeutic efficacy in an experimental model. Radiat Environ Biophys. 2012; 51(3):331-9. DOI: 10.1007/s00411-012-0419-8. View

19.

Rao M, Trivillin V, Heber E, Cantarelli M, Itoiz M, Nigg D . BNCT of 3 cases of spontaneous head and neck cancer in feline patients. Appl Radiat Isot. 2004; 61(5):947-52. DOI: 10.1016/j.apradiso.2004.05.016. View

20.

Kankaanranta L, Seppala T, Koivunoro H, Saarilahti K, Atula T, Collan J . Boron neutron capture therapy in the treatment of locally recurred head and neck cancer. Int J Radiat Oncol Biol Phys. 2007; 69(2):475-82. DOI: 10.1016/j.ijrobp.2007.03.039. View