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Pediatric CT scans and childhood leukemia
hospital databases to avoid recall bias, and also included the scanner model and use of contrast medium. As in other studies, the most common single CT scan in our analysis was a head scan.23
Radiation doses to RBM from the CT scans were calcu- lated using the best available methods, employing NCICT software, with age- and sex-specific phantoms and taking into account the scanner model. The scanning parameters entered into the software were based on the settings and procedures commonly used in Finland, although data were not available for each scan. We also evaluated the effects of choosing the most modern CT scanner at each imaging site and the OR showed robust behavior.
We also had data on several important risk factors includ- ing Down syndrome, parental socioeconomic status, large for gestational age and maternal smoking. We were able to incorporate data on cancer predisposing factors, which have been shown to be of importance recently.28,30 Inclusion of cases with Down syndrome would have increased the risk estimates, possibly because Down syndrome is associ- ated with increased risks of both leukemia and infections.4,40 We also explored the joint effect of Down syndrome and cumulative RBM dose and found no interaction. Subgroup analyses of exploratory nature were carried out by subtype of childhood leukemia and age at diagnosis, although these were underpowered.
Our study has some shortcomings. We were able to obtain data from all ten hospitals only after 2002, thus exposure assessment is not uniformly complete for sub- jects born prior to that year. Only a minor improvement in statistical power would have been reached by collect- ing pediatric CT scans from the rest of the imaging cen- ters in Finland. In addition, there is no reason to assume that the missed CT scans would have been unequally dis- tributed for the cases and controls, i.e. result in differen-
tial misclassification. For dose estimation, complete infor- mation on the scanning parameters is included in the modern picture archiving systems, but was not available before the year 2000. Use of parameters for each individ- ual scan would have provided more accurate dose esti- mates. The unexpectedly lower median dose of cases for older scanners found in our sensitivity analysis may be due to random error. The number of different CT scan- ners in our analysis was limited and thus the estimates of average dose were imprecise.
Our results support the notion that even small doses of radiation from pediatric CT scans produce a small, but detectable increase in leukemia risk. In the subgroup analyses, we observed no substantial differences by age or leukemia subtype, although slightly higher risks were found for precursor B-cell acute lymphoblastic leukemia.
Acknowledgments
The authors would like to thank Isabelle Thierry-Chef (IARC), Hannele Niiniviita (Turku University Hospital), Juha Suutari (STUK) and Rebecca Smith-Bindman (University of California, San Francisco) for their valuable suggestions and comments regarding modeling of CT scan doses with the data available in Finland. We are also grateful to Dr Choonsik Lee (National Cancer Institute) for his insightful comments related to modeling contrast media and for providing us with his state-of- the-art dose calculation software (NCICT) and Anniriikka Rantala (STUK) for collecting the data on CT scanners used in Finland. Päivi Laarne’s (Tampere University Hospital) crucial input regarding the scanning parameters enabled us to use NCICT software. Funding for the study was obtained from the Finnish Foundation for Pediatric Research, Väre Foundation for Pediatric Cancer Research and Competitive State Research Financing of the Expert Responsibility area of Tampere University Hospital (9T030 and 9U030).
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