The effects of low-dose radiation are being increasingly investigated in biological, epidemiological, and clinical studies. Many recent studies have indicated the beneficial effects of low doses of radiation, whereas some studies have suggested harmful effects even at low doses. This review article introduces various studies reporting both the beneficial and harmful effects of low-dose radiation, with a critique on the extent to which respective studies are reliable. Epidemiological studies are inherently associated with large biases, and it should be evaluated whether the observed differences are due to radiation or other confounding factors. On the other hand, well-controlled laboratory studies may be more appropriate to evaluate the effects of low-dose radiation. Since the number of such laboratory studies is steadily increasing, it will be concluded in the near future whether low-dose radiation is harmful or beneficial and whether the linear-no-threshold (LNT) theory is appropriate. Many recent biological studies have suggested the induction of biopositive responses such as increases in immunity and antioxidants by low-dose radiation. Based on recent as well as classical studies, the LNT theory may be out of date, and low-dose radiation may have beneficial effects depending on the conditions; otherwise, it may have no effects.

In hypofractionated stereotactic radiotherapy (SRT), high doses per fraction are usually used and the dose delivery pattern is different from that of conventional radiation. The daily dose is usually given intermittently over a longer time compared with conventional radiotherapy. During prolonged radiation delivery, sublethal damage repair takes place, leading to the decreased effect of radiation. In in vivo tumors, however, this decrease in effect may be counterbalanced by rapid reoxygenation. Another issue related to hypofractionated SRT is the mathematical model for dose evaluation and conversion. The linear–quadratic (LQ) model and biologically effective dose (BED) have been suggested to be incorrect when used for hypofractionation. The LQ model overestimates the effect of high fractional doses of radiation. BED is particularly incorrect when used for tumor responses in vivo , since it does not take reoxygenation into account. Correction of the errors, estimated at 5–20%, associated with the use of BED is necessary when it is used for SRT. High fractional doses have been reported to exhibit effects against tumor vasculature and enhance host immunity, leading to increased antitumor effects. This may be an interesting topic that should be further investigated. Radioresistance of hypoxic tumor cells is more problematic in hypofractionated SRT, so trials of hypoxia-targeted agents are encouraged in the future. In this review, the radiobiological characteristics of hypofractionated SRT are summarized, and based on the considerations, we would like to recommend 60 Gy in eight fractions delivered three times a week for lung tumors larger than 2 cm in diameter.