Effect of Total Treatment Time on Early Effects
Early responding tissues typically have a hierarchical organisation, with a population of stem cells that is constantly dividing to maintain population of differentiating cells. The main implication of this is that early responding tissues continue proliferating, and if treatment takes place over a longer period of time they will be able to withstand the dose more easily.
The other factor affecting early responding tissues and total treatment time is that early tissues may being repopulation after 1 - 2 weeks have elapsed of fractionated treatment. This repopulation involves increasing the numbers of dividing cells as well as shortening the cell cycle time. These cells are capable of countering a standard fractionation dose; therefore healing may occur if hyperfractionation without acceleration occurs.
In summary, total treatment time has a significant impact on the severity of early effects.
Effect of Fractionation on Early Effects
Fractionation, by itself, has little effect on the development of early effects. This occurs because cells of early responding tissues have a significant linear component of their cell survival curves - it is the total dose delivered, rather than the fractionation of dose, that determines the development of effects. This is in contrast to late effects, which show a significant dependence on the dose of individual fractions due to their quadratic cell survival curve. This is not to say that fractionation has no effect on early responding cells; the effect is simply much smaller than the effect of total dose and overall treatment time.
In summary, fractionation has minimal impact on the severity of early effects
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