Mechanistic modelling of radiotherapy-induced lung toxicity

This work explores the biological basis of a mechanistic model of radiation-induced lung damage; uniquely, the model makes a connection between the cellular radiobiology involved in lung irradiation and the full three-dimensional distribution of radiation dose.

Local tissue damage and loss of global organ function, in terms of radiation pneumonitis (RP), were modelled as different levels of radiation injury. Parameters relating to the former could be derived from the local dose-response function, and the latter from the volume effect of the organ. The literature was consulted to derive information on a threshold dose and volume-effect mechanisms.

Simulations of local tissue damage supported the alveolus as a functional subunit (FSU) which can be regenerated from a single surviving stem cell. A moderate interpatient variation in stem cell radiosensitivity (15%) resulted in a great variation in tissue response between 8 and 20 Gy. The threshold of FSU inactivation within a critical functioning volume leading to RP was found to be approximately 47% and the degree of health status variation (influencing the volume effect) in a population was estimated at 25%.

This work has shown that it is possible to make sense of the way the lung responds to radiation by modelling RP mechanistically, from cell death to tissue damage to loss of organ function.

Simulations were able to provide parameter values, currently not available in the literature, related to the response of the lung to irradiation.