Significance of low dose hypersensitivity in fractionated radiotherapy

Objective: To analyze the influences of the low radiation dose hypersensitivity (LDH) to the dose-effect relationship of fractionated radiotherapy. Methods: Collect data of LDH from literature and do curve fit for cell survival curve. Condition to join the data set: the lowest dose and dose increment in the experiment were less than 0.1 and 0.2 Gy, respectively. Based on parameters of the fit curve and fraction-effect relationship curve of fractionated irradiation were to be simulated. Result:(1) Four modes were classified according to cell's capacity of LDH and resistance to higher dose radiation. Mode A: LDH was not marked and radiation resistance could be seen in higher dose irradiation in these cells. Mode B: LDH was marked but radiation resistance could be seen in higher dose irradiation. Mode C: LDH was not marked but radiation sensitivity could be seen in higher dose irradiation. Mode D: LDH was marked and radiation sensitivity could be seen in higher dose irradiation. (2) The fraction-effect relationship curve was a multiphase curve: in very low fraction size (less than 0.3 Gy in V79), the curve came down rapidly with high dose efficiency. Subsequently, the speed of curve drop became so slow as to become negative in some cell lines with high LDH and the fraction dose efficiency declined comparing with low dose irradiation. After the above radiation resistant scope, which was about 0.5 to 1.0 Gy, the curve started to drop monotonically with the increment of dose according to the LQ Model. (3) According to the above fraction-effect curve, the sense of fraction modes that had been used in current radiotherapy should be reconsidered. Ultrafractionation: the dose efficiency of the radiation in low dose could be used adequately in this mode, so it may be a effective fractionation for cells with marked LDH such as in B or D cell. Hyperfractionation : this fractionation was designed to improve the total effect through increased total dose by upping of fraction number with downing of fraction size. As downing of fraction size would decrease the dose efficiency, whether the total effect being improved was not ensured. Routine mode with 1.5-2.5 Gy per fraction was a compromise between fraction efficiency and normal tissue protection. Hypofractionation with > 2.5 Gy per fraction was satisfactory in fraction efficiency, but special technology such as conformal radiation or heavy iron would have to be used to protect the normal tissue. Conclusions: The fraction-effect curve from 0.1 to several Gy of fraction size is a multiphase but not a monotonic fall curve that has been prefigured in LQ model. If the low dose hypersensitivity is considered, the small change of dose efficiency will lead to magnitude difference in total effect after multi-fractions radiotherapy for the role of exponentially enlarging fractionation. This multiphase fraction-effect curve is significant in the evaluation and determination of fractionation mode and protection of normal tissue in clinical practice of radiotherapy