Late toxicity of radiotherapy in Hodgkin's disease. The role of fraction size.

From 1972 to 1976 patients at the Gustave Roussy Institute were irradiated for Hodgkin's disease using a modified fractionation schedule (3 fractions of 3.3 Gy per week) for operational reasons. From 1964 to 1971 and from 1977 to 1981, a more conventional regimen (4 fractions of 2.5 Gy per week) was used. The rates of the late complications in these two subsets of patients treated with different fractionation schedules at the same total dose of 40 Gy during the same overall time were compared. Mediastinitis was observed in 19% of the '4 X 2.5 Gy/week' group versus 56% in the '3 X 3.3 Gy/week' group. Pericarditis in 0% versus 9%, gastroduodenal ulceration and severe gastritis in 10 versus 21% and small bowel obstruction in 5 versus 8%. When using the linear quadratic model with an alpha/beta of 2.5 Gy to evaluate the equivalent dose of 40 Gy given in 12 fractions of 3.3 Gy when delivered by fractions of 2.5 Gy, a value of 46.6 Gy is found. This difference of 6.6 Gy in the equivalent doses (for late toxicity) is likely to account for the significant increase of late radiation injuries, such as mediastinitis and pericarditis, in the present study. The local relapse rate was found to be slightly lower in the 3 X 3.3 Gy group. However, this possible benefit cannot offset the considerable increase of late complications.