ROLES OF RADIOTHERAPY AND SMOKING IN LUNG-CANCER FOLLOWING HODGKINS-DISEASE

Background: Several studies have shown that survivors of Hodgkin's dis ease have increased risk of lung cancer, but the factors responsible f or this excess risk are not well known. Purpose: This study was undert aken to investigate the effects of radiation dose, chemotherapy, and s moking on the risk of lung cancer following treatment of Hodgkin's dis ease. Methods: We conducted a case-control study in a cohort of 1939 p atients treated for Hodgkin's disease from 1966 through 1986 in The Ne therlands. Detailed treatment information was collected from the medic al records for 30 case patients with lung cancer following Hodgkin's d isease and 82 matched control subjects who had not developed lung canc er. Multiple sources were used to obtain as complete smoking histories of the study participants as possible. For each case-control set, the radiation dose received by the area of the lung where the case patien t developed the tumor was estimated on the basis of radiotherapy chart s and experimental simulations of treatments. The estimates of relativ e risk (RR) for lung cancer associated with specific exposures were ob tained from logistic regression methods, and all tests of statistical significance were two-sided. Results: A statistically significant incr ease in risk of lung cancer was observed with increasing radiation dos e (P for trend = .01) with an RR of 9.6 (95% confidence interval [CI] = 0.93-98) for patients who received 9 Gy or more compared with those who received less than 1 Gy. Patients who smoked more than 10 pack-yea rs after the diagnosis of Hodgkin's disease had a sixfold increase in the risk of lung cancer compared with patients who smoked less than 1 pack-year (P = .03). Positive interaction on a multiplicative scale wa s observed between the carcinogenic effects of smoking and radiation. The increase in risk of lung cancer with increasing radiation dose was much greater among the patients who smoked after diagnosis of Hodgkin 's disease than among those who refrained from smoking (P = .04). Ther e was no increase in lung cancer risk in relation to the number of cyc les of chemotherapy or the cumulative doses of the drugs mechlorethami ne and procarbazine. Conclusions: The excess risk of lung cancer in Ho dgkin's disease patients treated with radiotherapy is related to the r adiation dose received by the affected area of the lung. Smokers exper ience a significantly greater risk attributable to radiotherapy than n onsmokers. Implications: Physicians in charge of patient treatment sho uld make a special effort to dissuade Hodgkin's disease patients from smoking after receiving radiotherapy.