Advances in radiation treatment have resulted in lesser levels of normal tissue damage. Nonetheless, treatment-related morbidity remains a critical limiting factor. One of the goals of this work is to formulate a mechanistic model of normal tissue damage and its subsequent healing kinetics. Our premise is that post-irradiation normal tissue toxicity occurs when the loss of normal cells exceeds a threshold and that the extent of the toxicity is proportional to such a loss. Our model allows for estimating the probability distribution of various unobservable kinetic parameters that determine the time to injury onset and ensuing resolution. Another motivation for this work is the need to have a mechanistic biologically-based tool for extrapolating available empirical data on normal tissue damage to other treatment modalities (e.g. different temporal patterns of dose delivery or different radiation quality). We also noticed inadequacies in toxicity data collection - a deficiency this work will hopefully help ameliorate.

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