Site-Specific Cancer Incidence and Mortality After Cerebral Angiography with Radioactive Thorotrast

Details

• Personal Author:
  Anderson M ; Berger E ; Boice JD Jr. ; Gaul LK ; Goldman MB ; Hall P ; Hauptmann M ; Holm L-E ; Janower ML ; Land CE ; Monson RR ; Nyberg U ; Schottenfeld D ; Storm HH ; Travis LB
• Description:
  Few opportunities exist to evaluate the carcinogenic effects of long-term internal exposure to alpha-particle-emitting radionuclides. Patients injected with Thorotrast (thorium-232) during radiographic procedures, beginning in the 1930s, provide one such valuable opportunity. We evaluated site-specific cancer incidence and mortality among an international cohort of 3,042 patients injected during cerebral angiography with either Thorotrast (n = 1,650) or a nonradioactive agent (n = 1,392) and who survived 2 or more years. Standardized incidence ratios (SIR) for Thorotrast and comparison patients (Denmark and Sweden) were estimated and relative risks (RR), adjusted for population, age and sex, were generated with multivariate statistical modeling. For U.S. patients, comparable procedures were used to estimate standardized mortality ratios (SMR) and RR, representing the first evaluation of long-term, site-specific cancer mortality in this group. Compared with nonexposed patients, significantly increased risks in Thorotrast patients were observed for all incident cancers combined (RR = 3.4, 95% CI 2.9-4.1, n = 480, Denmark and Sweden) and for cancer mortality (RR = 4.0, 95% CI 2.5-6.7, n = 114, U.S.). Approximately 335 incident cancers were above expectation, with large excesses seen for cancers of the liver, bile ducts and gallbladder (55% or 185 excess cancers) and leukemias other than CLL (8% or 26 excess cancers). The RR of all incident cancers increased with time since angiography (P < 0.001) and was threefold at 40 or more years; significant excesses (SIR = 4.0) persisted for 50 years. Increasing cumulative dose of radiation was associated with an increasing risk of all incident cancers taken together and with cancers of the liver, gallbladder, and peritoneum and other digestive sites; similar findings were observed for U.S. cancer mortality. A marginally significant dose response was observed for the incidence of pancreas cancer (P = 0.05) but not for lung cancer. Our study confirms the relationship between Thorotrast and increased cancer incidence at sites of Thorotrast deposition and suggests a possible association with pancreas cancer. After injection with >20 ml Thorotrast, the cumulative excess risk of cancer incidence remained elevated for up to 50 years and approached 97%. Caution is needed in interpreting the excess risks observed for site-specific cancers, however, because of the potential bias associated with the selection of cohort participants, noncomparability with respect to the internal or external comparison groups, and confounding by indication. Nonetheless, the substantial risks associated with liver cancer and leukemia indicate that unique and prolonged exposure to alpha-particle-emitting Thorotrast increased carcinogenic risks. [Description provided by NIOSH]
• Subjects:
  Aging Carcinogens Environmental Exposure Men Mortality Neoplasms Occupational Health Radiation Risk Assessment Risk Factors Safety Women

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• Keywords:
  Age Groups Cancer Dose Response Exposure Levels Humans Models Mortality Rates Radiography Radionuclides Risk Factors Statistical Analysis

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• ISSN:
  0033-7587
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Maryland ; Massachusetts ; Michigan ; OSHA Region 1 ; OSHA Region 3 ; OSHA Region 5 ; OSHA Region 6 ; Texas
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  160
• Issue:
  6
• NIOSHTIC Number:
  nn:20059624
• Citation:
  Radiat Res 2003 Dec; 160(6):691-706
• Contact Point Address:
  Lois B. Travis, National Cancer Institute, Executive Plaza South, Suite 7086, Bethesda, MD 20892
• Email:
  travisl@mail.nih.gov
• CAS Registry Number:
  Thorium (CAS RN 7440-29-1)
• Federal Fiscal Year:
  2004
• Performing Organization:
  Harvard School of Public Health
• Peer Reviewed:
  True
• Start Date:
  20030701
• Source Full Name:
  Radiation Research
• End Date:
  20050630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:b3594194b164287c6e196884632351145e94da21075dc0ca01e4ed2c967febb0682fe902e57dd99d48c85b065f3b77ca2d92a4b10542e3feaa59bf0a4088d636
• Download URL:
  https://stacks.cdc.gov/view/cdc/223782/cdc_223782_DS1.pdf
• File Type:
  [PDF - 247.61 KB ]