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Volume and dose–response effects for severe symptomatic pneumonitis after fractionated irradiation of canine lung

Purpose : To study the dose-related incidence of severe symptomatic pneumonitis following fractionated irradiation applied to three different volumes of lung in normal beagle dogs. Materials and methods : A three-dimensional treatment planning system was used to design mediastinal fields of increasing width to irradiate 33%, 67% or 100% of both lungs combined in 128 normal beagle dogs. Total doses, ranging from 27 to 72 Gy, were delivered in 1.5Gy fractions over 6 weeks. Results : No dogs irradiated to 33% of their total lung volume developed severe symptomatic pneumonitis. In the 67% volume group, logistic fit of the data showed a dose–response curve with a 50% probability of developing severe symptomatic pneumonitis (ED50) after a total dose of 56.0 Gy (52.2–66.0 Gy, 95% confidence interval, CI). The more clinically relevant ED 5 for the first 6 months after irradiation of 67% of the lung was 48.1 Gy (18.5–52.0 Gy, 95% CI). The ED 50 and ED 5 values after irradiation of the whole lung (100%) were 44.1 Gy (41.2–53.5 Gy, 95% CI) and 39.1 Gy (8.8–41.8 Gy, 95% CI) respectively. Conclusion : Severe symptomatic pneumonitis proved to be a very informative volume-effect endpoint, clearly demonstrating that irradiated lung volume is a critical parameter to be considered in assigning thoracic radiotherapy treatment parameters. Volume effects in lung are dependent on the compensatory capacity of the nonirradiated lung. Underlying pathophysiology of irradiated tissue, as well as decreased compensatory capacity of nonirradiated tissue may have a strong effect on the dose-volume response.