Cancer mortality after nasopharyngeal radium irradiation in the Netherlands: a cohort study.

BACKGROUND: Nasopharyngeal radium irradiation (NRI) was used widely from 1940 through 1970 to treat otitis serosa in children and barotrauma in airmen and submariners. We assessed whether NRI-exposed individuals were at higher risk for cancer-related deaths than were nonexposed individuals. METHODS: We conducted a retrospective cohort study of all-cause and cancer-related mortality in 5358 NRI-exposed subjects and in 5265 frequency-matched nonexposed subjects, who as children were treated at nine ear, nose, and throat clinics in The Netherlands from 1945 through 1981. We recorded personal and medical data from original patient medical records and assessed vital status through follow-up at municipal population registries. Risk of mortality was evaluated by standardized mortality ratios (SMRs). All statistical tests were two-sided. RESULTS: The average radiation doses were 275, 10.9, 1.8, and 1.5 cGy for the nasopharynx, pituitary, brain, and thyroid, respectively. The median follow-up was 31.6 years. Three hundred two NRI-exposed subjects had died, with 269.2 deaths expected (SMR = 1.1; 95% confidence interval [CI] = 1.0 to 1.3); among nonexposed subjects, 315 died, with 283.5 deaths expected (SMR = 1.1; 95% CI = 0.99 to 1.2). Cancer-related deaths of 96 exposed subjects (SMR = 1.2; 95% CI = 0.95 to 1.4) and 87 nonexposed subjects (SMR = 1.0; 95% CI = 0.8 to 1.3) were documented. There were no excess deaths from cancers of the head and neck area among exposed subjects. However, there were excess deaths from cancers of lymphoproliferative and hematopoietic origin (SMR = 1.9; 95% CI = 1.1 to 3.0), mainly from non-Hodgkin's lymphoma (SMR = 2.6; 95% CI = 1.0 to 5.3). We found no evidence that breast cancer deaths were less than expected (SMR = 1.7; 95% CI = 0.9 to 2.8) in contrast to an earlier study. CONCLUSIONS: Our findings do not indicate an increased cancer mortality risk in a population exposed to NRI in childhood. More prolonged follow-up of this and other NRI cohorts is recommended.

Required treatment margin for coronary endovascular brachytherapy with iridium-192 seed ribbon.

PURPOSE: Preliminary clinical trials (SCRIPPS I, WRIST and Gamma 1) employing catheter-based endovascular brachytherapy (EVBT) with iridium-192 (Ir-192) seeds show promising results in reducing restenosis after coronary intervention. Failure analysis of these studies showed a significant number of restenosis at the treatment margin called "edge effect." The objective of this study is to investigate the factors that contribute to the adequacy of treatment margin. METHODS AND MATERIALS: The factors contributing to the margins are penumbra effect at the end of the seed train, uncertainty in target localization, longitudinal seed movement during cardiac cycle and barotrauma due to stent deployment. The magnitudes of the penumbra effect, which refers to the tapering off the prescribed isodose line near the ends of the source train, were calculated for various source lengths of Ir-192 seed ribbon using AAPM TG-43 algorithm. Uncertainty in target localization refers to the fact that the visual estimation of proximal and distal extent of the injury is not accurate, and this can be obtained by comparing the "estimate" from the interventional cardiologist with careful review of the cine-angiogram. Longitudinal seed movements relative to the coronary vessel during the cardiac cycle were determined by frame-by-frame reviewing cine-angiograms of 30 patients. The proximal and distal source points were measured in reference to branching vessels during the contrast phase of the cine-angiogram. The maximum proximal and distal longitudinal movement was captured and source displacement was measured from the closest proximal and distal branching vessel. Barotrauma, additional injury to the vessel arising from the stent deployment balloon, was obtained by reviewing specifications from commercially available stent delivery systems. RESULTS: The penumbra effect ranges from 3.9 to 4.5 mm for 6-22 Ir-192 seed ribbons. The uncertainty in target localization is within 3 mm for our interventional cardiologists. The results of seed movements were categorized by three major coronary vessels and by proximal versus distal ends. The mean and standard deviation of seed movement are 1.1 and 0.8 mm, respectively. The average length of barotrauma beyond the stent margins for reviewed stents was 1.7 mm, ranging from 0.5 to 2.5 mm. CONCLUSION: A minimum of 8-mm treatment margin is recommended for coronary vascular brachytherapy with Ir-192 seed ribbon. This was derived by considering the above contributing factors. Excessive margins should be avoided due to possible increase risk of late effect. By providing adequate treatment margins, one can avoid geographic miss; hence, one can further improve the effect of EVBT in reducing restenosis.