Altered fractionation outcomes for hypoxic head and neck cancer using the HYP-RT Monte Carlo model

Altered fractionation radiotherapy is simulated on a set of virtual tumours to assess the total doses required for tumour control compared with clinical head and neck data and the doses required to control hypoxic vs well-oxygenated tumours with different radiobiological properties.

The HYP-RT model is utilised to explore the impact of tumour oxygenation and the onset times of accelerated repopulation (AR) and reoxygenation (ROx) during radiotherapy. A biological effective dose analysis is used to rank the schedules based on their relative normal tissue toxicities.

Altering the onset times of AR and ROx has a large impact on the doses required to achieve tumour control. Immediate onset of ROx and 2-week onset time of AR produce results closely predicting average human outcomes in terms of the total prescription doses in clinical trials. Modifying oxygen enhancement ratio curves based on dose/fraction significantly reduces the dose (5-10 Gy) required for tumour control for hyperfractionated schedules. HYP-RT predicts 10×1.1 Gy per week to be most beneficial, whereas the conventional schedule is predicted as beneficial for early toxicity but has average-poor late toxicity.

HYP-RT predicts that altered radiotherapy schedules increase the therapeutic ratio and may be used to make predictions about the prescription doses required to achieve tumour control for tumours with different oxygenation levels and treatment responses.

Oxic and hypoxic tumours have large differences in total radiation dose requirements, affected by AR and ROx onset times by up to 15-25 Gy for the same fractionation schedule.