Cancer mortality following radium treatment for uterine bleeding

Cancer mortality in relation to radiation dose was evaluated among 4153 women treated with intrauterine radium (226Ra) capsules for benign gynecologic bleeding disorders between 1925 and 1965. Average follow up was 26.5 years (maximum = 59.9 years). Overall, 2763 deaths were observed versus 2687 expected based on U.S. mortality rates [standardized mortality ratio (SMR) = 1.03]. Deaths due to cancer, however, were increased (SMR = 1.30), especially cancers of organs close to the radiation source. For organs receiving greater than 5 Gy, excess mortality of 100 to 110% was noted for cancers of the uterus and bladder 10 or more years following irradiation, while a deficit was seen for cancer of the cervix, one of the few malignancies not previously shown to be caused by ionizing radiation. Part of the excess of uterine cancer, however, may have been due to the underlying gynecologic disorders being treated. Among cancers of organs receiving average or local doses of 1 to 4 Gy, excesses of 30 to 100% were found for leukemia and cancers of the colon and genital organs other than uterus; no excess was seen for rectal or bone cancer. Among organs typically receiving 0.1 to 0.3 Gy, a deficit was recorded for cancers of the liver, gall bladder, and bile ducts combined, death due to stomach cancer occurred at close to the expected rate, a 30% excess was noted for kidney cancer (based on eight deaths), and there was a 60% excess of pancreatic cancer among 10-year survivors, but little evidence of dose-response. Estimates of the excess relative risk per Gray were 0.006 for uterus, 0.4 for other genital organs, 0.5 for colon, 0.2 for bladder, and 1.9 for leukemia. Contrary to findings for other populations treated by pelvic irradiation, a deficit of breast cancer was not observed (SMR = 1.0). Dose to the ovaries (median, 2.3 Gy) may have been insufficient to protect against breast cancer. For organs receiving greater than 1 Gy, cancer mortality remained elevated for more than 30 years, supporting the notion that radiation damage persists for many years after exposure.