Skip to main content

Advertisement

Log in

Leukemia and brain tumors among children after radiation exposure from CT scans: design and methodological opportunities of the Dutch Pediatric CT Study

  • NEW STUDY
  • Published:
European Journal of Epidemiology Aims and scope Submit manuscript

Abstract

Computed tomography (CT) scans are indispensable in modern medicine; however, the spectacular rise in global use coupled with relatively high doses of ionizing radiation per examination have raised radiation protection concerns. Children are of particular concern because they are more sensitive to radiation-induced cancer compared with adults and have a long lifespan to express harmful effects which may offset clinical benefits of performing a scan. This paper describes the design and methodology of a nationwide study, the Dutch Pediatric CT Study, regarding risk of leukemia and brain tumors in children after radiation exposure from CT scans. It is a retrospective record-linkage cohort study with an expected number of 100,000 children who received at least one electronically archived CT scan covering the calendar period since the introduction of digital archiving until 2012. Information on all archived CT scans of these children will be obtained, including date of examination, scanned body part and radiologist’s report, as well as the machine settings required for organ dose estimation. We will obtain cancer incidence by record linkage with external databases. In this article, we describe several approaches to the collection of data on archived CT scans, the estimation of radiation doses and the assessment of confounding. The proposed approaches provide useful strategies for data collection and confounder assessment for general retrospective record-linkage studies, particular those using hospital databases on radiological procedures for the assessment of exposure to ionizing or non-ionizing radiation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Rehani MM, Berry M. Radiation doses in computed tomography. The increasing doses of radiation need to be controlled. BMJ. 2000;320(7235):593–4.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Pearce MS, Salotti JA, McHugh K, Metcalf W, Kim KP, Craft AW, et al. CT scans in young people in Northern England: trends and patterns 1993–2002. Pediatr Radiol. 2011;41(7):832–8.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Ware DE, Huda W, Mergo PJ, Litwiller AL. Radiation effective doses to patients undergoing abdominal CT examinations. Radiology. 1999;210(3):645–50.

    Article  CAS  PubMed  Google Scholar 

  4. http://globocan.iarc.fr/. Accessed 21 Jan 2014.

  5. United Nations Scientific Committee on the Effects of Atomic Radiation. UNSCEAR 2006 Report Vol. I. Effects of ionizing radiation, report of the General Assemble with Scientific Annexes. United Nations, New York, 2006.

  6. Cristy M. Active bone marrow distribution as a function of age in humans. Phys Med Biol. 1981;26(3):389–400.

    Article  CAS  PubMed  Google Scholar 

  7. Mathews JD, Forsythe AV, Brady Z, Butler MW, Goergen SK, Byrnes GB, et al. Cancer risk in 680,000 people exposed to computed tomography scans in childhood or adolescence: data linkage study of 11 million Australians. BMJ. 2013;346:f2360.

    Article  PubMed Central  PubMed  Google Scholar 

  8. Pearce MS, Salotti JA, Little MP, McHugh K, Lee C, Kim KP, et al. Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours: a retrospective cohort study. Lancet. 2012;380(9840):499–505.

    Article  PubMed Central  PubMed  Google Scholar 

  9. van Leeuwen FE, Klip H, Mooij TM, van de Swaluw AM, Lambalk CB, Kortman M, et al. Risk of borderline and invasive ovarian tumours after ovarian stimulation for in vitro fertilization in a large Dutch cohort. Hum Reprod. 2011;26(12):3456–65.

    Article  PubMed Central  PubMed  Google Scholar 

  10. Ronckers CM, Land CE, Verduijn PG, Hayes RB, Stovall M, van Leeuwen FE. Cancer mortality after nasopharyngeal radium irradiation in the Netherlands: a cohort study. J Natl Cancer Inst. 2001;93(13):1021–7.

    Article  CAS  PubMed  Google Scholar 

  11. Verloop J, van Leeuwen FE, Helmerhorst TJ, van Boven HH, Rookus MA. Cancer risk in DES daughters. Cancer Causes Control. 2010;21(7):999–1007.

    Article  PubMed Central  PubMed  Google Scholar 

  12. Karim-Kos HE, Kiemeney LA, Louwman MW, Coebergh JW, de Vries E. Progress against cancer in the Netherlands since the late 1980s: an epidemiological evaluation. Int J Cancer. 2012;130(12):2981–9.

    Article  CAS  PubMed  Google Scholar 

  13. http://federa.org/. Accessed 21 Jan 2014.

  14. NEMA. Digital imaging and communications in medicine (DICOM). http://medical.nema.org/. Accessed 21 Jan 2014.

  15. Jahnen A, Kohler S, Hermen J, Tack D, Back C. Automatic computed tomography patient dose calculation using DICOM header metadata. Radiat Prot Dosimetry. 2011;147(1–2):317–20.

    Article  CAS  PubMed  Google Scholar 

  16. Kim KP, Berrington de Gonzalez A, Pearce MS, Salotti JA, Parker L, McHugh K, et al. Development of a database of organ doses for paediatric and young adult CT scans in the United Kingdom. Radiat Prot Dosimetry. 2012;150(4):415–26.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Lee C, Kim KP, Long D, Fisher R, Tien C, Simon SL, et al. Organ doses for reference adult male and female undergoing computed tomography estimated by Monte Carlo simulations. Med Phys. 2011;38(3):1196–206.

    Article  PubMed Central  PubMed  Google Scholar 

  18. Lee C, Kim KP, Long DJ, Bolch WE. Organ doses for reference pediatric and adolescent patients undergoing computed tomography estimated by Monte Carlo simulation. Med Phys. 2012;39(4):2129–46.

    Article  PubMed Central  PubMed  Google Scholar 

  19. Lee C, Lodwick D, Hurtado J, Pafundi D, Williams JL, Bolch WE. The UF family of reference hybrid phantoms for computational radiation dosimetry. Phys Med Biol. 2010;55(2):339–63.

    Article  PubMed Central  PubMed  Google Scholar 

  20. Kroll ME, Stiller CA, Murphy MF, Carpenter LM. Childhood leukaemia and socioeconomic status in England and Wales 1976–2005: evidence of higher incidence in relatively affluent communities persists over time. Br J Cancer. 2011;105(11):1783–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Poole C, Greenland S, Luetters C, Kelsey JL, Mezei G. Socioeconomic status and childhood leukaemia: a review. Int J Epidemiol. 2006;35(2):370–84.

    Article  PubMed  Google Scholar 

  22. Pearce MS, Salotti JA, McHugh K, Kim KP, Craft AW, Lubin J, et al. Socio-economic variation in CT scanning in Northern England, 1990–2002. BMC Health Serv Res. 2012;12:24.

    Article  PubMed Central  PubMed  Google Scholar 

  23. van Duin C, Keij I. Sociaal-economische status indicator op postcodeniveau. Maandstatistiek van de bevolking. 2002;50:32–5.

    Google Scholar 

  24. Seif AE. Pediatric leukemia predisposition syndromes: clues to understanding leukemogenesis. Cancer Genet. 2011;204(5):227–44.

    Article  PubMed  Google Scholar 

  25. Freeman SB, Taft LF, Dooley KJ, Allran K, Sherman SL, Hassold TJ, et al. Population-based study of congenital heart defects in Down syndrome. Am J Med Genet. 1998;80(3):213–7.

    Article  CAS  PubMed  Google Scholar 

  26. Hauptmann M, Meulepas JM. CT scans in childhood and risk of leukaemia and brain tumours. Lancet. 2012;380(9855):1736–7.

    Article  PubMed  Google Scholar 

  27. Traubici J. The double bubble sign. Radiology. 2001;220(2):463–4.

    Article  CAS  PubMed  Google Scholar 

  28. www.eurocatnederland.nl. Accessed 21 Jan 2014.

  29. Brasme JF, Morfouace M, Grill J, Martinot A, Amalberti R, Bons-Letouzey C, et al. Delays in diagnosis of paediatric cancers: a systematic review and comparison with expert testimony in lawsuits. Lancet Oncol. 2012;13(10):e445–9.

    Article  PubMed  Google Scholar 

  30. Berrington de Gonzalez A, Mahesh M, Kim KP, Bhargavan M, Lewis R, Mettler F, et al. Projected cancer risks from computed tomographic scans performed in the United States in 2007. Arch Intern Med. 2009;169(22):2071–7.

    Article  PubMed  Google Scholar 

  31. Brenner D, Elliston C, Hall E, Berdon W. Estimated risks of radiation-induced fatal cancer from pediatric CT. Am J Roentgenol (AJR). 2001;176(2):289–96.

    Article  CAS  Google Scholar 

  32. Chodick G, Ronckers CM, Shalev V, Ron E. Excess lifetime cancer mortality risk attributable to radiation exposure from computed tomography examinations in children. Isr Med Assoc J. 2007;9(8):584–7.

    PubMed  Google Scholar 

  33. EPI-CT: design and epidemiological methods of an international study on cancer risks after paediatric CT. In preparation 2013. http://epi-ct.iarc.fr/.

  34. Thierry-Chef I, Dabin J, Friberg EG, Hermen J, Istad TS, Jahnen A, et al. Assessing organ doses from paediatric CT scans—a novel approach for an epidemiology study (the EPI-CT study). Int J Environ Res Public Health. 2013;10(2):717–28.

    Article  PubMed Central  PubMed  Google Scholar 

  35. Goede-Bolder A, Cnossen MH, Dooijes D, Van den Ouweland AM, Niermeijer MF. From gene to disease; neurofibromatosis type 1. Ned Tijdschr Geneeskd. 2001;145(36):1736–8.

    PubMed  Google Scholar 

  36. Evans DG, Howard E, Giblin C, Clancy T, Spencer H, Huson SM, et al. Birth incidence and prevalence of tumor-prone syndromes: estimates from a UK family genetic register service. Am J Med Genet A. 2010;152A(2):327–32.

    Article  CAS  PubMed  Google Scholar 

  37. Weijerman ME, van Furth AM, Vonk Noordegraaf A, van Wouwe JP, Broers CJ, Gemke RJ. Prevalence, neonatal characteristics, and first-year mortality of Down syndrome: a national study. J Pediatr. 2008;152(1):15–9.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We sincerely thank all hospitals who provided and will provide data for our study. Without the dedicated support by numerous professionals in the participating radiology departments, this study would not be possible. This study was funded by the European Community Seventh Framework Programme (FP7/2007–2013) under Grant Agreement Number 269912—EPI-CT: ‘Epidemiological study to quantify risks for paediatric computerized topography and to optimise doses’ and by the Association for International Cancer Research (AICR) with Grant 12-1155. Dr. Ronckers is supported by the Dutch Cancer Society. Funders had no involvement in the study design, data collection, analysis and interpretation, the writing of the report, or the decision to submit the paper for publication.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michael Hauptmann.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Meulepas, J.M., Ronckers, C.M., Smets, A.M.J.B. et al. Leukemia and brain tumors among children after radiation exposure from CT scans: design and methodological opportunities of the Dutch Pediatric CT Study. Eur J Epidemiol 29, 293–301 (2014). https://doi.org/10.1007/s10654-014-9900-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10654-014-9900-9

Keywords

Navigation