Gilbert, E. S., Stovall, M., Gospodarowicz, M., van Leeuwen, F. E., Andersson, M., Glimelius, B., Joensuu, T., Lynch, C. F., Curtis, R. E., Holowaty, E., Storm, H., Pukkala, E., van't Veer, M. B., Fraumeni, J. F., Jr., Boice, J. D., Jr., Clarke, E. A. and Travis, L. B. Lung Cancer after Treatment for Hodgkin's Disease: Focus on Radiation Effects. Radiat. Res. 159, 161–173 (2003).
Aspects of radiation-induced lung cancer were evaluated in an international study of Hodgkin's disease. The study population consisted of 227 patients with lung cancer and 455 matched controls. Unique features included dose determinations to the specific location in the lung where each cancer developed and quantitative data on both chemotherapy and tobacco use obtained from medical records. The estimated excess relative risk (ERR) per Gy was 0.15 (95% CI: 0.06–0.39), and there was little evidence of departure from linearity even though lung doses for the majority of Hodgkin's disease patients treated with radiotherapy exceeded 30 Gy. The interaction of radiation and chemotherapy that included alkylating agents was almost exactly additive, and a multiplicative relationship could be rejected (P = 0.017). Conversely, the interaction of radiation and smoking was consistent with a multiplicative relationship, but not with an additive relationship (P < 0.001). The ERR/Gy for males was about four times that for females, although the difference was not statistically significant. There was little evidence of modification of the ERR/Gy by time since exposure (after a 5-year minimum latent period), age at exposure, or attained age. Because of the very high radiation doses received by Hodgkin's disease patients and the immunodeficiency inherent to this lymphoma and that associated with chemotherapy, generalizing these findings to other populations receiving considerably lower doses of radiation should be done cautiously.