Analysis of normal tissue complication probability of the lung using a reliability model

Area of Science:

• Radiation oncology
• Biophysics
• Medical physics

Background:

• The volume effect is crucial for predicting normal tissue complication probability (NTCP) after partial irradiation.
• Conformal radiation therapy aims to reduce late sequelae by considering organ-at-risk irradiation.
• A reliability model with parallel functional subunits (FSU) was previously developed for NTCP calculation.

Purpose of the Study:

• To analyze published mouse lung data using the FSU model.
• To estimate the critical fraction (k/N) and spatial distribution of FSUs for radiation-induced lung injury.
• To investigate the causes of volume effect variation in the mouse lung.

Main Methods:

• Analysis of published data on radiation-induced lethal pneumonitis and altered breathing rate in mouse lungs.
• Application of a reliability model assuming parallel functional subunits (FSU).
• Estimation of critical fraction (k/N) and spatial density distribution of FSUs.

Main Results:

• A critical fraction (k/N) of 0.7 provided a good fit to the experimental data for both endpoints.
• The critical fraction did not vary spatially within the lung.
• Volume effect variations are likely due to heterogeneous spatial distribution of FSU density or inactivation probability.

Conclusions:

• The critical fraction for radiation-induced lung injury in mice is approximately 0.7.
• Spatial heterogeneity in FSU density or inactivation probability, not tissue architecture, explains volume effect variations.
• The FSU model effectively analyzes radiation effects on normal tissues.