Original Paper

Radiation and Environmental Biophysics

, Volume 48, Issue 3, pp 263-274

Open Access This content is freely available online to anyone, anywhere at any time.

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

  • Igor ShuryakAffiliated withCenter for Radiological Research, Columbia University Medical Center
  • , Philip HahnfeldtAffiliated withCaritas St. Elizabeth’s Medical Center, Tufts University School of Medicine
  • , Lynn HlatkyAffiliated withCaritas St. Elizabeth’s Medical Center, Tufts University School of Medicine
  • , Rainer K. SachsAffiliated withDepartments of Mathematics and Physics, University of California Berkeley
  • , David J. BrennerAffiliated withCenter for Radiological Research, Columbia University Medical Center Email author 

Abstract

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.