RADIATION-INDUCED LUNG DAMAGE AFTER THORACIC IRRADIATION FOR HODGKINS-DISEASE - THE ROLE OF FRACTIONATION

Purpose: to estimate the alpha/beta ratio for damage to human lung aft er thoracic irradiation for Hodgkin's disease. Patients and methods: T he criterion for lung injury was the presence of radiological changes in the vicinity of the mediastinum as assessed on regular follow-up ch est X-ray examinations. Patients with supradiaphragmatic stage I-II Ho dgkin's disease received mantle field irradiation as part of their tre atment between 1964 and 1981 (E.O.R.T.C, protocols H1, H2, and 115). T he total mediastinal doses fixed by the protocols were 35-40 Gy. The f ractional doses were left to the decision of the physicians in charge: the most frequent regimens were 5 x 1.8, 5 x 2.0, 4 x 2.5 and 3 x 3.3 Gy per week. The data were fit to the linear-quadratic (L.Q.) model u sing time-to-injury as endpoint. Results: 1048 (97%) of 1082 patients were evaluable. The mean follow-up duration was 8 years. One hundred a nd ninety-five cases of radiologically-visible lung damage were observ ed after a median interval of 6 months (range: 0-101), The 3-year actu arial probability of lung damage was 19%(95% confidence limits: 17, 21 ). Multivariate analysis (Cox model, stratified by protocol) showed an increased risk of damage with dose per fraction (relative risk, R.R. = 2.22 per Gy (1.75, 2.82)), the presence of systemic symptoms (R.R. = 1.53 (1.09, 2.15)), and total mediastinal dose (R.R. = 1.06 per Gy (1 .01, 1.12)). Age, sex, histological type, number of involved nodal sit es and radiotherapy duration did not significantly modify the risk of lung damage. The L.Q. model parameters were: alpha = 0.031 Gy(-1) (0.0 03, 0.059), beta = 0.010 Gy(-2) (0.007, 0.013), alpha/beta = 3.07 Gy ( -0.23, 8.46), Conclusion: this low alpha/beta ratio is consistent with late effects values from animals and humans, and illustrates the infl uence of large fraction sizes on the occurrence of late pulmonary comp lications.