Local stem cell depletion model for radiation myelitis.

We propose a model for normal tissue damage based on the assumption that adult mammalian stem cells have limited mobility and, consequently, for each organ, there is a maximum volume (the "critical volume," Vc), that can be repopulated and repaired by a single surviving stem cell. This concept is applied to a simple, 1-dimensional model of the spinal cord, where the critical volume is a "slice" of "thickness," t, assumed to be small compared to lengths of spinal cord usually irradiated clinically. The probability of myelitis is explicitly obtained as a function of the dose, dose per fraction, length of cord irradiated, slice thickness, number of stem cells per slice and parameters alpha and beta of the stem cell survival curve. The complication probability is expressed as a triple negative exponential function of dose analogous to the double negative exponential function for tumor control, resulting in a steep dose-response curve with short tails in both the high dose and low dose regions. We show that the model predictions are compatible with the experimental data for radiation myelitis in the rat. We discuss how this concept can be applied to other organs such as skin and to organs composed of structurally and functionally distinct subunits, such as the kidney.