Objective The research consists of epidemiological studies of the radiation includes effects in patients injected with radium-224. The study more than 1500 ankylosing spondylitis patients treated between 1948 and 1975 with repeated intravenous injections of radium-224. The causes of death, and occurrence other lesions possibly related to the radium-224 treatment, are analysed and compared with results in a control group of ankylosing spondylitis patients not treated with radioactive drugs or X-rays. Comparisons were made with respect to the risk of bone tumours, leukaemias, kidney and liver diseases, and other diseases known, or supposed to be related to radium-224 treatment.In the exposure group, 3 cases of malignant tumours in the skeleton have been observed and in the control group only one skeletal tumour, has been observed.For cancers in the skeleton there might be a slight indication of an increased incidence in exposure group whereas in the control group the observed cases are within the limitations of expected cases.At 3 year intervals we followed the health of 900 patients (509 men, 173 women, 111 boys and 107 girls) who received repeated injections of radium-224 after World War 2, as treatment of ankylosing spondylitis or bone tuberculosis, but also for other noncancerous diseases.Bone sarcomas occurred in 54 patients, with 2 developing a second primary sarcoma, giving a total of 56 bone sarcomas (compared to 0.2 to 0.3 cases expected naturally). Thus we conclude that virtually all of these bone sarcomas were radiation induced. The dose response has been fitted to a linear quadratic exponential equation and the wave shaped distribution of tumour appearance times has been analysed.There were 102 observed soft tissue malignancies, and this number is close to the expectation for the age of distribution and person years of observation.The breast cancer excess came as a surprise with 15 cases observed versus the 4.1 to 6.1 cases expected. All but one case occurred more than 10 years after irradiation and all but one occurred after the age of 35.Liver cancer occurred in 6 radium-224 patients (ie in a significantly larger number than the 1.1 to 1.2 expected cases).Other cancers have not yet shown a significant excess in the radium-224 patients. These include stomach, lung, skin, uterus, ovary, prostate, bladder and brain cancers and multiple myeloma.The research aimed at the further development of mathematical methods for the analysis of the dose, age, and time dependences of radiation induced neoplasms. It was equally concerned with the application of these methods to animal studies and to epidemiological investigations. Work concentrated on:the statistical and mathematical evaluation of data from radium-224 follow up studies;methodological work aimed at the improvement of the mathematical methods that are equally applicable to animal studies and epidemiological investigations of radiation carcinogenesis.Spiess, Mays, and Stefani had earlier in their follow up of the radium-224 patients recognised an increased frequency of lens opacifications. In the few cases with detailed ophthalmological investigations they were able to see typical characteristics of radiation induced cataracts. Our analysis has demonstrated that almost all of the early cataracts (ie those appearing before an age of roughly 53 years) were due to radium-224 injections. In line with the postulate of a nonstochastic radiation effect (ie radiation action on a multiplicity of cells) the dosage dependence was found to be consistent with a threshold of about 5E5 beguerels radium-224 per kg bodyweight.A major effort in the research was aimed at the assessment of a possible dose rate dependence for radium-224 induced bone sarcomas. A nonparametric maximum likelihood fit was employed to identify the underlying dose and dose rate dependence quantitatively. This led to the remarkable finding that one obtains linear dose dependences for the radium-224 induced bone sarcomas, if different doses (ie different injected activities) are given within a constant time. In contrast one obtains linear quadratic dependences, when the dose rate is constant (ie when higher doses are given within proportionallyextended time periods). Fields of science medical and health sciencesclinical medicineoncologyliver cancermedical and health sciencesclinical medicinepneumologytuberculosismedical and health sciencesclinical medicineoncologybreast cancermedical and health sciencesclinical medicinehepatologymedical and health sciencesclinical medicineoncologyleukemia Programme(s) FP1-RADPROT 6C - Multiannual research and training programme (Euratom) in the field of radiation protection, 1985-1989 Topic(s) Data not available Call for proposal Data not available Funding Scheme CSC - Cost-sharing contracts Coordinator GSF - FORSCHUNGSZENTRUM FUER UMWELT UND GESUNDHEIT GMBH EU contribution No data Address Ingolstaedter Landstrasse 1 85764 NEUHERBERG Germany See on map Links Website Opens in new window Total cost No data
