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A new view of radiation-induced cancer: integrating short- and long-term processes. Part I: Approach

2009; Springer Science+Business Media; Volume: 48; Issue: 3 Linguagem: Inglês

10.1007/s00411-009-0230-3

1432-2099

Igor Shuryak, Philip Hahnfeldt, Lynn Hlatky, Rainer K. Sachs, David J. Brenner,

Mathematical Biology Tumor Growth

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.