Estimation of the spatial distribution of target cells for radiation pneumonitis in mouse lung

Purpose: Recent studies of Liao et al. and Travis et al. have demonstrated that irradiation of cross-sectional partial volumes contiguous to the base of mouse lung produces a higher incidence of pneumonitis than irradiation of equally sized subvolumes contiguous to the apex. One interpretation of this finding is that the critical target cells for pneumonitis are not distributed uniformly throughout the lung. The purpose of the present study was to test this interpretation by obtaining an estimate of the spatial distribution of the critical target cells for pneumonitis in mouse lung, based on the partial-volume data. Methods and Materials: A mathematical model was derived describing the probability of radiation pneumonitis as a function of dose, volume of lung irradiated, and location in the lung of the irradiated subvolume. The model includes a nonparametric description of the spatial target-cell distribution in lung, to be estimated from data. The model was fitted to the lethality data of Liao et al. and Travis et al. to obtain estimates of the proportion of target cells contained in each of various subvolumes of the lung. Results: The results indicate that the critical target cells in mouse lung are concentrated in the base and, to a somewhat lesser extent, in the apex of the lung, with fewer cells in the middle region. The estimated spatial distribution of target cells in mouse lung agrees well with the distribution of alveoli, whose concentration in the midlung is limited by the presence of the major conducting airways. Conclusion: Heterogeneity in the spatial distribution of critical target cells in normal tissue implies that the complication probability (NTCP) depends on the location in the organ of the irradiated subvolume, as well as on radiation dose and subvolume size. Calculations using an NTCP model for mouse lung indicate that irradiation of equal subvolumes of lung with the same dose can lead to complication probabilities covering the full range from 0 to 100%, depending only on the location in the lung of the irradiated subvolume.