Long-term cardiac morbidity and mortality in a randomized trial of pre- and postoperative radiation therapy versus surgery alone in primary XXXX .

@entity1 @entity0 @entity16 @entity741 @entity583 @entity204 @entity65
BACKGROUND AND PURPOSE: Some types of radiation therapy have been associated with an increased risk of cardiac mortality and morbidity in @entity1 with @entity0 . A relationship has been observed between cardiac radiation dose-volume and the level of excess risk of cardiac mortality. However, relatively few data are available on the morbidity from @entity583 associated with adjuvant radiotherapy. @entity1 AND METHODS: From 1971 to 1976, a total of 960 @entity1 with operable @entity0 were randomly allocated to preoperative radiation therapy, postoperative radiation therapy or to surgery alone. A previous analysis of the cardiac dose-volumes with the treatment techniques used in the trial indicated that the irradiated @entity1 could roughly be divided into three groups. Information on the number of @entity583 was obtained through computerized record linkage with a population-based registry of @entity583 in Stockholm County. Information on cause-specific mortality was obtained from the Swedish Cause-of-Death Registry. The median follow-up was 20 years (range 17-23 years). RESULTS: A total of 58 @entity1 developed an @entity583 during the period of follow-up. The number of @entity583 cases was not significantly different between the three treatment groups. When analyzed according to estimated cardiac radiation dose-volumes, @entity1 in the highest dose-volume subgroup exhibited a hazard of @entity583 of 1.3 (95% CI 0.7-2.6) relative to that of the surgical controls, whereas the corresponding relative hazard for the intermediate and low dose-volume subgroups was below unity. Data on @entity204 due to @entity65 showed that @entity1 in the high dose-volume group exhibited a hazard of 2.0 (95% CI 1.0-3.9, P = 0.04) relative to that of the surgical controls. Concerning @entity204 due to @entity741 , the relative hazard for the same subgroup was 2.5 (95% CI 1.1-5.7, P = 0.03). The difference between the groups was established after 4-5 years. The cumulative incidence curves continued to diverge up to about 10-12 years. No further divergence appeared after 12 years, but the number of events was low. CONCLUSIONS: This analysis confirms and extends previous results from the trial. Cardiac mortality was positively correlated with the cardiac dose-volume. @entity1 receiving high dose-volumes exhibited an increased mortality of @entity741 , but not of @entity583 , which implies another mechanism, e.g. radiation-induced @entity16 to the heart.
