Radiation-induced lung damage after thoracic irradiation for Hodgkin's disease: the role of fractionation.
OBJECTIVE
to estimate the alpha/beta ratio for damage to human lung after thoracic irradiation for Hodgkin's disease.


METHODS
The criterion for lung injury was the presence of radiological changes in the vicinity of the mediastinum as assessed on regular follow-up chest X-ray examinations. Patients with supradiaphragmatic stage I-II Hodgkin's disease received mantle field irradiation as part of their treatment between 1964 and 1981 (E.O.R.T.C. protocols H1, H2, and H5). The total mediastinal doses fixed by the protocols were 35-40 Gy. The fractional 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 using time-to-injury as endpoint.


RESULTS
1048 (97%) of 1082 patients were evaluable. The mean follow-up duration was 8 years. One hundred and ninety-five cases of radiologically-visible lung damage were observed after a median interval of 6 months (range: 0-101). The 3-year actuarial 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 sites and radiotherapy duration did not significantly modify the risk of lung damage. The L.Q. model parameters were: alpha = 0.031 Gy-1 (0.003, 0.059), beta = 0.010 Gy-2 (0.007, 0.013), alpha/beta = 3.07 Gy (-0.23, 8.46).


CONCLUSIONS
this low alpha/beta ratio is consistent with late effects values from animals and humans, and illustrates the influence of large fraction sizes on the occurrence of late pulmonary complications.
E.O.R.T.C. Lymphoma Cooperative Group, M.D. Anderson Cancer Center, Houston, Texas, USA.
B
B
Dubray
M
M
Henry-Amar
J H
JH
Meerwaldt
E M
EM
Noordijk
D O
DO
Dixon
J M
JM
Cosset
H D
HD
Thames
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006689:Hodgkin Disease / Q000532:radiotherapy*; D006801:Humans; D016014:Linear Models; D008168:Lung / Q000528:radiation effects*; D008297:Male; D008480:Mediastinitis / Q000209:etiology; D008875:Middle Aged; D015999:Multivariate Analysis; D011832:Radiation Injuries / Q000209:etiology*; D011878:Radiotherapy / Q000009:adverse effects; D011879:Radiotherapy Dosage; D012307:Risk Factors; D013899:Thoracic Neoplasms / Q000532:radiotherapy*