Mortality after radiological investigation with radioactive Thorotrast: a follow-up study of up to fifty years in Portugal.

Cerebral angiography using a radioactive radiological contrast medium, Thorotrast, was pioneered by Moniz in Portugal in the 1920s. Thorotrast is retained by the reticuloendothelial system, with a biological half-life of several hundred years, so that such patients suffer lifetime exposure to internal radiation. We studied mortality in Portuguese patients who were administered Thorotrast during the period 1928-1959 and in a comparison group of patients who received nonradioactive contrast agents. There were 1096 systemically exposed, 1014 unexposed, and, unique to the Portuguese study, 240 locally exposed Thorotrast patients who were successfully traced and followed up to the end of 1996. Mortality was significantly raised among systemically exposed Thorotrast patients relative to those unexposed for all causes [relative risk (RR) = 2.63], all neoplasms (RR = 6.72), liver cancer (RR = 42.4), chronic liver disease (RR = 5.12), other non-neoplastic diseases of the digestive system (RR = 4.87), neoplastic (RR = 21.9) and non-neoplastic hematological disorders (RR = 6.00), and non-neoplastic diseases of the respiratory system (RR = 4.31). Risks for most of these conditions increased significantly with time since first administration of the contrast medium and with cumulative alpha-particle radiation dose. Mortality was also significantly raised for non-neoplastic disorders of the nervous system (RR = 12.7) and ill-defined conditions (RR = 3.74), but these associations are likely to reflect the initial diagnosis, not Thorotrast exposure, because risks declined significantly with time and/or dose. There were no significant excess deaths from oropharyngeal or nasal cancers, or from any other cause, among patients exposed to Thorotrast locally for visualization of the perinasal sinuses, and no clear trend in risk with time since exposure. This study shows an association between systemic, but not local, exposure to Thorotrast and mortality from liver cancer, chronic liver disease, and neoplastic and non-neoplastic hematological disorders, with risks for these conditions remaining high for over 40 years after administration. Liver conditions, but not hematological disorders, showed a strong and consistent gradient with cumulative alpha-particle radiation dose.