A new view of radiation-induced cancer: integrating short- and long-term processes. Part I: Approach
- Author(s): Shuryak, Igor
- Hahnfeldt, Philip
- Hlatky, Lynn
- Sachs, Rainer K.
- Brenner, David J.
- et al.
Published Web Locationhttps://doi.org/10.1007/s00411-009-0230-3
Mathematical models of radiation carcinogenesis are important for understanding mechanisms and for interpreting or extrapolating risk. There are two classes of such models: (1) long-term formalisms that track pre-malignant cell numbers throughout an entire lifetime but treat initial radiation dose–response simplistically and (2) short-term formalisms that provide a detailed initial dose–response even for complicated radiation protocols, but address its modulation during the subsequent cancer latency period only indirectly. We argue that integrating short- and long-term models is needed. As an example of this novel approach, we integrate a stochastic short-term initiation/inactivation/repopulation model with a deterministic two-stage long-term model. Within this new formalism, the following assumptions are implemented: radiation initiates, promotes, or kills pre-malignant cells; a pre-malignant cell generates a clone, which, if it survives, quickly reaches a size limitation; the clone subsequently grows more slowly and can eventually generate a malignant cell; the carcinogenic potential of pre-malignant cells decreases with age.