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 pneumoni tis following fractionated irradiation applied to three different volumes o f lung in normal beagle dogs. Materials and methods: A three-dimensional treatment planning system was us ed to design mediastinal fields of increasing width to irradiate 33%, 67% o r 100% of both lungs combined in 128 normal beagle dogs. Total doses, rangi ng from 27 to 72 Gy, were delivered in 1.5 Gy fractions over 6 weeks. Results: No dogs irradiated to 33% of their total lung volume developed sev ere symptomatic pneumonitis. In the 67% volume group, logistic fit of the d ata showed a dose-response curve with a 50% probability of developing sever e symptomatic pneumonitis (ED50) after a total dose of 56.0 Gy (52.2-66.0 G y, 95% confidence interval, CI). The more clinically relevant ED5 for the f irst 6 months after irradiation of 67% of the lung was 48.1 Gy (18.5-52.0 G y, 95% CI). The ED50 and ED5 values after irradiation of the whole lung (10 0%) were 44.1 Gy (41.2-53.5 Gy, 95% CI) and 39.1 Gy (8.8-41.8 Gy, 95% CI) r espectively. Conclusion: Severe symptomatic pneumonitis proved to be a very informative volume-effect endpoint, clearly demonstrating that irradiated lung volume i s a critical parameter to be considered in assigning thoracic radiotherapy treatment parameters. Volume effects in lung are dependent on the compensat ory capacity of the nonirradiated lung. Underlying pathophysiology of irrad iated tissue, as well as decreased compensatory capacity of nonirradiated t issue may have a strong effect on the dose-volume response.