Time Course for the Hazard of Radiation-induced Pneumonitis Death in Mice

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Abstract
The form of the hazard function for radiation-induced pneumonitis death in mice was investigated. ‘Hazard’ refers to the instantaneous failure rate at a specified time, conditional upon non-failure to that time. Thus, the hazard function describes the time profile for the risk of pneumonitis death among still-surviving subjects. Single-dose lethality data from nine previously published studies involving irradiation of the lung were combined. Sufficient data were then available to estimate the hazard for eight different dose groups (dose range 12–15 Gy). The results of this study suggest that there are multiple distinct peaks in the hazard function for radiation pneumonitis, corresponding to distinct waves of death separated by an average interval of 33 days. The times of the peak hazards are dose dependent, with the peak hazards occurring earlier after larger doses, and the values of the hazards at the peaks are also dose dependent, with larger doses corresponding to a greater risk of death. The implications of a multiply-peaked hazard function for the possible mechanisms of response to whole-lung irradiation are discussed.