Optimization of tumour control probability in hypoxic tumours by radiation dose redistribution: a modelling study

Tumour hypoxia is a known cause of clinical resistance to radiation therapy. The purpose of this work was to model the effects on tumour control probability (TCP) of selectively boosting the dose to hypoxic regions in a tumour, while keeping the mean tumour dose constant. A tumour model with a continuous oxygen distribution, incorporating pO2 histograms published for head and neck patients, was developed. Temporal and spatial variations in the oxygen distribution, non-uniform cell density and cell proliferation during treatment were included in the tumour modelling. Non-uniform dose prescriptions were made based on a segmentation of the tumours into four compartments. The main findings were: (1) Dose redistribution considerably improved TCP for all tumours. (2) The effect on TCP depended on the degree of reoxygenation during treatment, with a maximum relative increase in TCP for tumours with poor or no reoxygenation. (3) Acute hypoxia reduced TCP moderately, while underdosing chronic hypoxic cells gave large reductions in TCP. (4) Restricted dose redistribution still gave a substantial increase in TCP as compared to uniform dose boosts. In conclusion, redistributing dose according to tumour oxygenation status might increase TCP when the tumour response to radiotherapy is limited by chronic hypoxia. This could potentially improve treatment outcome in a subpopulation of patients who respond poorly to conventional radiotherapy