General properties of different models used to predict normal tissue complications due to radiation

In the current study the author analyzes general properties of three different models used to predict normal tissue complications due to radiation: (1) Surviving fraction of normal cells in the framework of the linear quadratic (LQ) equation for cell kill, (2) the Lyman-Kutcher-Burman (LKB) model for normal tissue complication probability (NTCP), and (3) generalized equivalent uniform dose (gEUD). For all considered cases the author assumes fixed average dose to an organ of interest. The author's goal is to establish whether maximizing dose uniformity in the irradiated normal tissues is radiobiologically beneficial. Assuming that NTCP increases with increasing overall cell kill, it is shown that NTCP in the LQ model is maximized for uniform dose. Conversely, NTCP in the LKB and gEUD models is always smaller for a uniform dose to a normal organ than that for a spatially varying dose if parameter n in these models is small (i.e., n <1). The derived conflicting properties of the considered models indicate the need for more studies before these models can be utilized clinically for plan evaluation and/or optimization of dose distributions. It is suggested that partial-volume irradiation can be used to establish the validity of the considered models.