Is there an optimum overall time for head and neck radiotherapy? A review, with new modelling

To test by modelling whether a non-standard fractionated schedule giving optimum log cell kill could be expected, between short (accelerated) and longer multiple fraction/day schedules.

Linear quadratic modelling was carried out for many schedules, with biologically effective doses converted to normalised total doses (NTDs; in 2 Gy fractions). Late complication and acute mucosal NTDs were calculated as constraint doses for each schedule, and the highest tumour NTDs and log cell kill values within both constraints were calculated. This modelling is robust and agrees with conclusions in a very recent meta-analysis (Bourhis J, Overgaard J, Audry H, et al. Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis. www.thelancet.com. Published online August 17, 2006).

The six schedules that gave the highest tumour log cell kill deliver a narrow range of 11.1-11.2 log10 cell kill in the present parameters. Other regularly used schedules give closer to 10 log10. Using one fraction/day fails to achieve the highest therapeutic ratios. Suggestions are made for escalating certain UK schedules. Fractionated radiotherapy results in a nearly constant tumour cell kill if the acute mucosal NTD is held constant. However, a small (3%) gain in tumour cell kill occurs from 3 weeks to 73 fractions of 1.15 Gy in 7 weeks. That is how fractionation works, within both acute and late constraints. Short accelerated schedules enable fewer late complications, but do not do as well for the minority of head and neck tumours that repopulate slowly.

Schedules of 4-6 weeks overall time could be chosen to give at least 11 log10 cell kill, which are safe. Most tumours would require two fractions/day, until routine monitoring of repopulation rates becomes feasible to select individual tumours. There is no 'optimum schedule', but each chosen schedule can be balanced against its own risk of excessive acute or late complications, as shown in these examples.