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

Summary: 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 6week interval in terms of inhibitory effect on tumor development, toxicity and DNA synthesis. We performed a double application, 6weeks 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 8months. 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 2months 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 1week 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 8months post-BNCT. A double application of BPA-BNCT and (GB-10+BPA)-BNCT, 6weeks apart, could be used therapeutically at no additional cost in terms of radiotoxicity in normal and dose-limiting tissues. [Copyright &y& Elsevier]