title: Boron Neutron Capture Therapy (BNCT) in an oral precancer model: therapeutic benefits and potential toxicity of a double application of BNCT with a six-week interval.
abstract: Given the clinical relevance of locoregional recurrences in head and neck cancer, we developed a novel experimental model of premalignant tissue in the hamster cheek pouch for long-term studies and demonstrated the partial inhibitory effect of a single application of Boron Neutron Capture Therapy (BNCT) on tumor development from premalignant tissue. The aim of the present study was to evaluate the effect of a double application of BNCT with a 6 week interval in terms of inhibitory effect on tumor development, toxicity and DNA synthesis. We performed a double application, 6 weeks apart, of (1) BNCT mediated by boronophenylalanine (BPA-BNCT); (2) BNCT mediated by the combined application of decahydrodecaborate (GB-10) and BPA [(GB-10+BPA)-BNCT] or (3) beam-only, at RA-3 nuclear reactor and followed the animals for 8 months. The control group was cancerized and sham-irradiated. BPA-BNCT, (GB-10+BPA)-BNCT and beam-only induced a reduction in tumor development from premalignant tissue that persisted until 8, 3, and 2 months respectively. An early maximum inhibition of 100% was observed for all 3 protocols. No normal tissue radiotoxicity was detected. Reversible mucositis was observed in premalignant tissue, peaking at 1 week and resolving by the third week after each irradiation. Mucositis after the second application was not exacerbated by the first application. DNA synthesis was significantly reduced in premalignant tissue 8 months post-BNCT. A double application of BPA-BNCT and (GB-10+BPA)-BNCT, 6 weeks apart, could be used therapeutically at no additional cost in terms of radiotoxicity in normal and dose-limiting tissues.
authors.affiliation: Department of Radiobiology, National Atomic Energy Commission, Argentina.
authors.forename: Andrea
authors.initials: A
authors.lastname: Monti Hughes
authors.forename: Emiliano C C
authors.initials: EC
authors.lastname: Pozzi
authors.forename: Elisa M
authors.initials: EM
authors.lastname: Heber
authors.forename: Silvia
authors.initials: S
authors.lastname: Thorp
authors.forename: Marcelo
authors.initials: M
authors.lastname: Miller
authors.forename: Maria E
authors.initials: ME
authors.lastname: Itoiz
authors.forename: Romina F
authors.initials: RF
authors.lastname: Aromando
authors.forename: Ana J
authors.initials: AJ
authors.lastname: Molinari
authors.forename: Marcela A
authors.initials: MA
authors.lastname: Garabalino
authors.forename: David W
authors.initials: DW
authors.lastname: Nigg
authors.forename: Verónica A
authors.initials: VA
authors.lastname: Trivillin
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Schwint
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000008:administration & dosage*; D016754:Boron Neutron Capture Therapy / Q000009:adverse effects / Q000379:methods*; D002610:Cheek; D006224:Cricetinae; D004247:DNA / Q000096:biosynthesis; D004195:Disease Models, Animal; D009062:Mouth Neoplasms / Q000532:radiotherapy*; D052016:Mucositis / Q000209:etiology; D010649:Phenylalanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D011230:Precancerous Conditions / Q000532:radiotherapy*; D011833:Radiation Injuries, Experimental; D016896:Treatment Outcome
chemical_list: D001896:Boron Compounds; C569622:decahydrodecaborate; D010649:Phenylalanine; D004247:DNA; C033685:4-boronophenylalanine