Modeling of normal tissue response to radiation: the critical volume model

A model for calculating normal tissue complication probability in response to therapeutic doses of radiation is presented.

The model which we call the "critical volume model" is based on a concept of functional subunits defined either structurally (e.g., nephrons) or functionally, and an assumption that normal tissue complication probability is fully determined by the number or fraction of surviving functional subunits composing an organ or tissue. The essential features of the model are that it takes into account variations in tissue radiosensitivity and architecture of an organ for a single patient and for a patient population, and predicts the normal tissue complication probability under conditions of 3-dimensional inhomogeneity of the dose distribution. The model can be used for Integral Response, or "parallel," organs (where all functional subunits are performing the same function in parallel and the output of the organ is the sum of the outputs of the functional subunits and for Critical Element, or "serial," organs (where damage to one functional subunit results in an expression of damage for the whole organ). The model combines into one compact scheme new concepts and several ideas and models which have been previously developed by other investigators.

The behavior of the model is presented and discussed for the example of the kidney, with clinical nephritis as the functional endpoint.

The model has the potential to be a useful tool for evaluation and optimization of 3-dimensional treatment plans for a variety of types of normal tissues.