Abstract
Over one million European children undergo computed tomography (CT) scans annually. Although moderate- to high-dose ionizing radiation exposure is an established risk factor for hematological malignancies, risks at CT examination dose levels remain uncertain. Here we followed up a multinational cohort (EPI-CT) of 948,174 individuals who underwent CT examinations before age 22 years in nine European countries. Radiation doses to the active bone marrow were estimated on the basis of body part scanned, patient characteristics, time period and inferred CT technical parameters. We found an association between cumulative dose and risk of all hematological malignancies, with an excess relative risk of 1.96 (95% confidence interval 1.10 to 3.12) per 100 mGy (790 cases). Similar estimates were obtained for lymphoid and myeloid malignancies. Results suggest that for every 10,000 children examined today (mean dose 8 mGy), 1–2 persons are expected to develop a hematological malignancy attributable to radiation exposure in the subsequent 12 years. Our results strengthen the body of evidence of increased cancer risk at low radiation doses and highlight the need for continued justification of pediatric CT examinations and optimization of doses.
Main
The use of computed tomography (CT) has grown rapidly in most high-income countries1 since its introduction2 at the beginning of the 1970s. Although the benefits of CT imaging in patient management are undisputed, the potential increased cancer risk3 and relatively high cumulative doses incurred from multiple scans have raised concerns in the medical and scientific community, leading to a plateauing/reduction in number of pediatric CTs in many countries4,5,6 and a reduction in pediatric doses7. A number of alternative modalities, including fast-acquisition magnetic resonance imaging and ultrasonography are now replacing CT examinations for specific pediatric indications8. Despite this, up to 7% of all CT procedures in high-income countries are performed on children2.
While moderate-dose (≥100 mGy) to high-dose (≥1 Gy) ionizing radiation exposure is a well-established risk factor for leukemia, in both children and adults9,10, the risk associated with childhood and adolescent low-dose exposure (<100 mGy), the dose range typically associated with diagnostic CT examinations, is unclear. This is especially concerning given that CT scanning is the largest contributor to the world’s average annual effective dose per person from medical radiation sources, in both children and adults2,11.
Several studies estimated the hematological malignancies risk associated with CT scan radiation in children and young adults in large-scale national cohort12,13,14,15,16,17,18 and case–control studies19,20. Although results of most individual studies12,13,17,20 and a recent meta-analysis21 suggest an increased risk of leukemia associated with repeated CT examinations, studies were criticized due to low statistical power, inadequate individual dosimetry and potential bias from confounding by indication (when those who undergo CT examinations are at higher risk of cancer than those who do not, due to underlying conditions)22. Current international radiological protection recommendations23 are, therefore, mainly based on linear extrapolations of risk from the higher doses of the Japanese atomic bomb survivor studies24. These extrapolations, which assume no dose threshold below which the risk of radiation-induced cancer is zero (the linear no threshold model of risk), are controversial10,25.
The EPI-CT study, coordinated by the International Agency for Research on Cancer (IARC), was set up to overcome limitations of previous national studies and improve direct estimates of cancer risk from low-dose radiation exposure from CT scanning in childhood and adolescence. It included 948,174 individuals from nine European countries26. In this Article, we present the EPI-CT analyses of risk of hematological malignancies in relation to radiation exposure from CT examinations in childhood, adolescence and early adulthood.
Results
Descriptive analyses
The analysis included 876,771 individuals, who underwent 1,331,896 CT examinations (mean 1.52, standard deviation (s.d.) 1.46 CT examinations per patient) and were followed up for at least 2 years following their first CT. They contributed 6,863,833 person-years (PYs) of follow-up (Table 1). We identified 790 hematological malignancies (subtype distribution in Supplementary Table 1), including 578 cases of lymphoid malignancies and 203 cases of myeloid malignancies and acute leukemia (AL). Mean follow-up was 7.8 years (6.5 years for cases). Fifty-one percent of the cases were younger than 20 years at diagnosis (ranging from 38% among mature T and natural killer (NK) cell neoplasms to 82% among precursor cell neoplasms), whereas 88.5% (range 76–99%) were younger than 30 years (Table 1 and Supplementary Table 2)….
