The relationship between the sensitivity of cells to high-energy photons and the RBE of particle radiation used in radiotherapy.

The relationship between relative biological effectiveness in the limit of zero dose (RBE(1)) and the LET of radiation is examined and compared for several cell lines, including cells from patients with ataxia telangiectasia, in the context of a microdosimetric-kinetic (MK) model of cell killing by radiation. Evidence is presented that the sensitivity of a cell to low-LET photon radiation, as measured by the linear parameter of the linear-quadratic cell survival relationship (alpha), is largely determined by its vulnerability to formation of a lethal lesion from transformation of a single potentially lethal lesion (PLL) in DNA, as opposed to formation by combination of two PLL. As a result, the RBE(1) of cells that are relatively less sensitive to low-LET photon radiation increases more with increasing LET than the RBE(1) of cells that are more sensitive to low-LET radiation. As a consequence, a pair of cells that have clearly different sensitivity to low-LET radiation tend to have more nearly the same sensitivity as the LET increases into the range of 100 to 200 keV microm(-1). Cells with the same, or nearly the same, sensitivity to low-LET photon radiation continue to have nearly the same sensitivity as the LET is similarly increased. Thus there may be a radiobiological advantage to treatment with high-LET particle radiation for situations in which the target tumor cells are less radiosensitive than the cells that determine the tolerance of the normal tissue at risk. This may be the case for treatment of many of the common malignancies that occur in adults. This general principle may be helpful in selection of patients for treatment with particle radiation, such as carbon ions, and in the design of clinical trials to determine the optimal dose and fractionation schedules for such treatment.