Radiogenic responses of normal cells induced by fractionated irradiation--a simulation study. Part II. Late responses

Based on controlled theory, a computed simulation model has been constructed which describes the time course of slowly responding normal cells after irradiation exposure. Subsequently, different clinical irradiation schemes are compared in regard to their delayed radiogenic responses referred to as late effects in radiological terminology.

A cybernetic model of a parenchymal tissue consisting of dominantly resting functional cells has been developed and transferred into a computer model. The radiation effects are considered by characteristic cell parameters as well as by the linear-quadratic model.

Three kinds of tissue (brain and lung parenchyma of the mouse, liver parenchyma of rat) have been irradiated in the model according to standard-, super-, hyperfractionation and a single high dose per week. The simulation studies indicate that the late reaction of brain parenchyma to hyperfractionation (3 x 1.5 Gy per day) and of lung parenchyma tissue with regard to all fractionation schemes applied is particularly severe. In contrast to these observations the behavior of liver parenchyma is not unique: If Dtotal amounts to 60 Gy there is no evidence for compensation of radiation damages, but if Dtotal is restricted to 30 Gy the corresponding evidence can be expected for all schemes. In the case of a high single dose of 6 Gy a reduction of the recovery time from 1 week to 2...2 days yields also an indication of a severe damage, even if Dtotal amounts only to 30 Gy.

A comparison of the simulation results basing to the survival of cell numbers with clinical experience and practice shows that the clinical reality can qualitatively be represented by the model. This opens the door for connecting side effects to normal tissue with the corresponding tumor efficacy (discussed in previous papers). The model is open to further refinement and to discussions referring to the phenomenon of late effects.