Effects of variations in overall treatment time on the clonogenic survival of V79-4 cells: Implications for radiosurgery.
Hallgren S., Hill MA., Thompson JM., Elliott A., Paddick I., Jones B., Hopewell JW.
The importance of effects related to the repair of sublethal radiation damage as treatment duration varies, partly a function of dose-rate, is a current controversy in clinical radiosurgery. Cell survival studies have been performed to verify the importance of this effect in relation to established models. Mammalian V79-4 cells were irradiated in vitro with γ-rays, either as an acute exposure in a few minutes, where the effects of sublethal irradiation damage repair over the period of exposure can be ignored, or as protracted exposures delivered over 15-120 min. Protraction was achieved either by introducing a variable time gap between two doses of 7 Gy, or as a continuous exposure at lower dose rates so that a range of doses were delivered in fixed times of 30, 60 or 120 min. For all doses there was a progressive reduction in efficacy with increasing overall treatment time. This was illustrated by the progressive increase in clonogenic cell survival with a resulting right shift of the survival curves. Cell survival curves for irradiations given either as an acute exposure (6.1 Gy/min), over fixed times (30, 60 and 120 min) or for a fixed low dose-rate (0.2 Gy/min) were well fitted by the Linear Quadratic (LQ) model giving an α/β ratio of 4.0 Gy and a single repair half-time of 31.5 min. The present results are consistent with published data with respect to the response of solid tumors and normal tissues, whose response to both continuous and fractionated irradiation is also well described by the LQ model. This suggests the need for dose compensation in radiosurgical treatments, and other forms of radiotherapy, where dose is delivered over a similar range of protracted overall treatment times, perhaps as a prerequisite to full biological effective dose treatment planning.