LAUSR

PURPOSE Intrinsic radioresistance and increased proliferation rates in head and neck cancers (HNCs) are associated with negative radiotherapy (RT) treatment responses. The use of gold nanoparticles (AuNPs) as radiosensitisers could enable total radiation dose reduction and lowered radiation-toxicity. AuNP radiosensitisation may overcome hypoxia-induced radioresistence and treatment-induced accelerated repopulation of cancer cells in HNCs, improving radiotherapy outcomes. METHODS Tumour control was determined by considering individual cancer cell responses in probabilistic computational simulations using HYP-RT software for clinical radiotherapy doses and fractionation schedules along with 3 different nanoparticle administration schedules. Antagonistic tumour hypoxia and rapid tumour regrowth due to accelerated repopulation of cancers cells were taken into consideration. RESULTS Simulations indicate that tumours that are conventionally uncontrollable can be controlled with AuNP radiosensitisation. In simulations where the absence of AuNPs required radiotherapy doses above standard clinical prescriptions, reoccurring AuNP administration allowed for radiation-dose reductions below standard clinical dose prescriptions. For example, considering a 2 Gy per fraction radiotherapy schedule, tumour control was achieved with 57.2 ± 5.1 Gy (p = <0.0001) for weekly AuNP administration and 53.0 ± 4.0 Gy (p = <0.0001) for bi-weekly AuNP administration compared to 69.9 ± 5.8 Gy with no radiosensitisation. CONCLUSIONS AuNPs decreased predicted RT total doses required to achieve tumour control via total stem cell elimination, offering an optimistic prediction and method for which hypoxia-induced and rapidly growing radioresistant tumours are treated more effectively. Outcomes are also shown to be sensitive to the RT schedule with data for hyperfractionated RT indicating greatest benefits from radiosensitisation.