Abstract
It is well known that exposures like those from 226Ra, 224Ra and Thorotrast® injections increase the risk of neoplasia in bone marrow and liver. The thorium-based radioactive contrast agent Thorotrast® was introduced in 1929 and applied worldwide until the 1950s, especially in angiography and arteriography. Due to the extremely long half-life of several hundred years and the life-long retention of the thorium dioxide particles in the human body, patients suffer lifetime internal exposure. The health effects from the incorporated thorium were investigated in a few cohort studies with a German study being the largest among them. This retrospective cohort study was set up in 1968 with a follow-up until 2004. The study comprises 2326 Thorotrast patients and 1890 patients of a matched control group. For those being alive at the start of the study in 1968 follow-up was done by clinical examinations on a biannual basis. For the others, causes of death were collected in various ways. Additionally, clinical, radiological and biophysical studies of patients were conducted and large efforts were made to best estimate the radiation doses associated with incorporation of the Thorotrast. The aim of this paper is to describe the cohort, important results and some open questions. The data from the German Thorotrast Study are available to other interested researchers. Information can be found at http://storedb.org.
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References
Andersson M, Carstensen B, Storm HH (1995a) Mortality and cancer incidence after cerebral arteriography with or without Thorotrast. Radiat Res 142:305–320
Andersson M, Wallin H, Jonsson M, Nielsen LL, Visfeldt J, Vyberg M, Bennett WP, de Benedetti VM, Travis LB, Storm HH (1995b) Lung carcinoma and malignant mesothelioma in patients exposed to Thorotrast: incidence, histology and p53 status. Int J Cancer 63:330–336
Bast T, Zuna I, Layer G, van Kaick G (1995) CT-measurements of liver and spleen in Thorotrast patients and their influence to dose rate calculations. In: van Kaick G, Karaoglou A, Kellerer AM (eds) Health effects of internally deposited radionuclides: emphasis on radium and thorium. World Scientific, Singapore New Jersey, pp 235–239
Bauer KH (1943) Thorotrast und Krebsgefahr. Chirurg 15:204–207
Becker N, Liebermann D, Wesch H, van Kaick G (2008) Mortality among Thorotrast-exposed patients and an unexposed comparison group in the German Thorotrast Study. Eur J Cancer 44:1259–1268
Birschwilks M, Gruenberger M, Adelmann C, Tapio S, Gerber G, Schofield PN, Grosche B (2011) The European radiobiological archives: online access to data from radiobiological experiments. Radiat Res 175:526–531
Dalheimer AR, Kaul A (1989) Calculation of local dose to tissues adjacent to Thorotrast conglomerates. In: Taylor DM (ed) Risks from radium and Thorotrast: proceedings of a workshop held in Bethesda, Maryland, USA from 3 to 5 October 1989 (BIR Report 21). Brit Inst Radiol, London, pp 108–111
Dalheimer AR, Kaul A, Said MD (1988) Analysis of tissue samples containing colloidal thorium dioxide (Thorotrast) or zirconium dioxide (Zirconotrast): radiochemical preparation and alpha-spectrometry. Sci Total Environ 70:335–353
DIMDI (Deutsches Institut für Medizinische Dokumentation und Information) (2004) ICD-10-GM Version 2005. Band I: Systematisches Verzeichnis. Internationale statistische Klassifikation der Krankheiten und verwandter Gesundheitsprobleme, 10. Revision. German Modification. Systematisches Verzeichnis. Stuttgart Berlin, Kohlhammer
dos Santos Silva I, Malveiro F, Jones ME, Swerdlow AJ (2003) Mortality after radiological investigation with radioactive Thorotrast: a follow-up study of up to fifty years in Portugal. Radiat Res 159:521–534
Grillmaier R (1984) Thoron exhalation. In: van Kaick G, Muth H, Kaul A (eds) The German Thorotrast Study. Results of epidemiological, clinical and biophysical examinations on radiation-induced late effects in man caused by incorporated colloidal thorium dioxide (Thorotrast). Office for Official Publications of the European Communities, Luxembourg, pp 162–167
Grillmaier R, Muth H (1971) Radiation dose distribution in lungs of thorotrast patients. Health Phys 20:409–419
Gruenberger M, Schofield PN, Birschwilks M, Grosche B (2016) STORE database. http://www.storedb.org/. Accessed 23 Mar 2016
Hornik S, Kaul A (1995) The calculated alpha-dose and lung cancer risk in Thorotrast patients. In: van Kaick G, Karaoglou A, Kellerer AM (eds) Health effects of internally deposited radionuclides: emphasis on radium and thorium. World Scientific, Singapore New Jersey, pp 43–46
IARC (2001) Ionizing radiation, part 2, some internally deposited radionuclides. IARC monographs on the evaluation of carcinogenic risks to humans, vol 78. International Agency for Research on Cancer, Lyon
Immich H (1973) Statistical problems of thorotrast studies. In: Faber M (ed) Proceedings of the third international meeting on the toxicity of thorotrast, held at The Finsen Institute, Copenhagen 25–27 April 1973 (Risø Report 294). Roskilde, Danish Atomic Energy Commission Research Establishment Risø, pp 148–150
Janower ML (1973) Follow-up of thorotrast patients from Boston, Massachusetts and Ann Arbor, Michigan, USA. In: Faber M (ed) Proceedings of the third international meeting on the toxicity of thorotrast, held at The Finsen Institute, Copenhagen 25–27 April 1973 (Risø Report 294). Roskilde, Danish Atomic Energy Commission Research Establishment Risø, pp 126–136
Kaul A (1995) Biokinetic models and data. In: van Kaick G, Karaoglou A, Kellerer AM (eds) Health effects of internally deposited radionuclides: emphasis on radium and thorium. World Scientific, Singapore New Jersey, pp 53–67
Kaul A, Muth H (1978) Thorotrast kinetics and radiation dose: results from studies in thorotrast patients and from animal experiments. Radiat Environ Biophys 15:241–259
Kaul A, Noffz W (1978) Tissue dose in thorotrast patients. Health Phys 35:113–121
Kaul A, Pustelnik B, Pustelnik C, Riedel W (1986) Assessment of thorotrast: redistribution in liver tissue of the rat. In: Goessner W (ed) The radiobiology of radium and thorotrast: proceedings of a symposium, Neuherberg, 29–31 October 1984. Urban und Schwarzenberg, München, pp 189–195
Kemmer W, Steinstrasser A, Muth H (1979) Chromosome aberrations as a biological dosimeter in thorotrast patients: dosimetric problems. Environ Res 18:178–183
Kunkel R, Bader R, Werner B (1984) Whole-body counter measurements. In: van Kaick G, Muth H, Kaul A (eds) The German Thorotrast Study. Results of epidemiological, clinical and biophysical examinations on radiation-induced late effects in man caused by incorporated colloidal thorium dioxide (Thorotrast). Office for Official Publications of the European Communities, Luxembourg, pp 148–161
Liebermann D, Lührs H, van Kaick G (1995) Late effects of paravascular Thorotrast deposits. In: van Kaick G, Karaoglou A, Kellerer AM (eds) Health effects of internally deposited radionuclides: emphasis on Radium and Thorium. World Scientific, Singapore New Jersey, pp 271–274
Little MP, Azizova TV, Bazyka D, Bouffler SD, Cardis E, Chekin S et al (2012) Systematic review and meta-analysis of circulatory disease from exposure to low-level ionizing radiation and estimates of potential population mortality risks. Environ Health Perspect 120:1503–1511
Lloyd RD, Wrenn ME, Taylor GN, Mays CW, Jee WS, Bruenger FW, Miller SC, Paschoa AS (1985) Toxicity of 228Ra and 228Th relative to 226Ra for bone sarcoma induction in beagles. Strahlentherapie Sonderb 80:65–69
Lührs H, Liebermann D, Wesch H, van Kaick G (1995) Therapeutic results of Thorotrast patients with primary liver cancer. In: van Kaick G, Karaoglou A, Kellerer AM (eds) Health effects of internally deposited radionuclides: emphasis on Radium and Thorium. World Scientific, Singapore New Jersey, pp 267–270
Marsh JW, Blanchardon E, Gregoratto D, Hofmann W, Karcher K, Nosske D, Tomasek L (2012) Dosimetric calculations for uranium miners for epidemiological studies. Radiat Prot Dosimetry 149:371–383
Martling U, Mattsson A, Travis LB, Holm LE, Hall P (1999) Mortality after long-term exposure to radioactive Thorotrast: a forty-year follow-up survey in Sweden. Radiat Res 151:293–999
Mays CW, Spiess H (1979) Bone tumors in thorotrast patients. Environ Res 18:88–93
Mori T, Kido C, Fukutomi K, Kato Y, Hatakeyama S, Machinami R, Ishikawa Y, Kumatori T, Sasaki F, Hiroto Y, Kiyosawa K, Hayashi S, Tanooka H, Sobue T (1999) Summary of entire Japanese thorotrast follow-up study: updated 1998. Radiat Res 152:S84–S87
Muth H (1989) History of the German Thorotrast studies. Motivation and development of the studies in relation to similar investigations in other countries. In: Taylor DM (ed) Risks from radium and thorotrast: proceedings of a workshop held in Bethesda, Maryland, USA from 3 to 5 October 1989 (BIR Report 21). Brit Inst Radiol, London, pp 93–97
NRC National Research Council (1988) Health risks of radon and other internally deposited alpha-emitters (BEIR IV). National Academy Press, Washington, DC
Scharfstaedt A (1997) Die Kalkulation der mittleren Dosisleistung bei Thorotrastpatienten unter Berücksichtigung paravasaler Ablagerungen. Dissertation, University of Heidelberg
Schlemmer HP, Liebermann D, Naser V, van Kaick G (2000) Locoregional late effects of paravascular thorotrast deposits: results of the German thorotrast study. J Neuroradiol 27:253–263
Spiess H (2010) Life-span study on late effects of 224-Ra in children and adults. Health Phys 99:286–291
Spiethoff A, Wesch H, Wegener K, Hanisch E, Kaul A (1994) Translocation of Thorotrast in the body. Radiat Res 138:409–414
Tirmarche M, Harrison JD, Laurier D, Paquet F, Blanchardon E, Marsh JW (2010) ICRP Publication 115: lung cancer risk from radon and progeny and statement on radon. Ann ICRP 40:1–64
Travis LB, Land CE, Andersson M, Nyberg U, Goldman MB, Knudson Gaul L, Berger E, Storm HH, Hall P, Auvinen A, Janower ML, Holm LE, Monson RR, Schottenfeld D, Boice JD (2001) Mortality after cerebral angiography with or without radioactive Thorotrast: an international cohort of 3,143 two-year survivors. Radiat Res 156:136–150
Travis LB, Hauptmann M, Gaul LK, Storm HH, Goldman MB, Nyberg U, Berger E, Janower ML, Hall P, Monson RR, Holm LE, Land CE, Schottenfeld D, Boice JD, Andersson M (2003) Site-specific cancer incidence and mortality after cerebral angiography with radioactive thorotrast. Radiat Res 160:691–706
van Kaick G, Drings P, Loholter H (1973) Chronic myeloid leukemia 27 years after Thorotrast incorporation. Strahlentherapie 145:582–587
van Kaick G, Lorenz D, Muth H, Kaul A (1978) Malignancies in German thorotrast patients and estimated tissue dose. Health Phys 35:127–136
van Kaick G, Wesch H, Lührs H, Liebermann D, Kaul A, Muth H (1989) The German Thorotrast Study—report on 20 years follow-up. In: Taylor DM (ed) Risks from radium and thorotrast: proceedings of a workshop held in Bethesda, Maryland, USA from 3 to 5 October 1989 (BIR Report 21). Brit Inst Radiol, London, pp 98–104
van Kaick G, Wesch H, Lührs H, Liebermann D, Kaul A (1991) Neoplastic diseases induced by chronic alpha-irradiation—epidemiological, biophysical and clinical results of the German Thorotrast Study. J Radiat Res 32(Suppl 2):20–33
van Kaick G, Dalheimer A, Hornik S, Kaul A, Liebermann D, Lührs H, Spiethoff A, Wegener K, Wesch H (1999) The German thorotrast study: recent results and assessment of risks. Radiat Res 152:S64–S71
Wegener K (1984) Pathoanatomy. In: van Kaick G, Muth H, Kaul A (eds) The German Thorotrast Study. Results of epidemiological, clinical and biophysical examinations on radiation-induced late effects in man caused by incorporated colloidal thorium dioxide (Thorotrast). Office for Official Publications of the European Communities, Luxembourg, pp 42–68
Wick RR, Chmelevsky D, Gössner W (1985) 224Ra: risk to bone and haematopoietic tissue in ankylosing spondylitis patients. Strahlentherapie Sonderb 80:38–44
Acknowledgments
The authors gratefully acknowledge the work of the many former scientists and technical staff who contributed to the German Thorotrast Study. The authors are deeply indebted to Ms Jutta Helber: over many years she put enormous efforts in the final data preparation.
Funding
The German Thorotrast Study was supported by the German federal authorities and the radiation protection programme—EURATOM—of the Commission of the European Communities through different contracts. STORE was and is funded under contract numbers 232628 (STORE), 249689 (DoReMi) and 662287 (CONCERT) from the EC EURATOM Programme. Additional funding came from the German Ministry for the Environment, contract no. 3613S70035.
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For this type of study, i.e. a review, formal consent is not required, but informed consent was obtained from all individual participants included in those parts of the cited studies which included examinations.
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A Kaul: Formerly Federal Office for Radiation Protection, Salzgitter, Germany.
H Wesch, G van Kaick: Formerly German Cancer Research Center, Heidelberg, Germany.
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Grosche, B., Birschwilks, M., Wesch, H. et al. The German Thorotrast Cohort Study: a review and how to get access to the data. Radiat Environ Biophys 55, 281–289 (2016). https://doi.org/10.1007/s00411-016-0651-8
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DOI: https://doi.org/10.1007/s00411-016-0651-8