Medical Imaging and Pediatric and Adolescent Hematologic Cancer Risk

Abstract

Background: Assessing the risk of radiation-induced hematologic cancer from medical imaging in children and adolescents might support informed decisions on the use of imaging.

Methods: We followed a retrospective cohort of 3,724,623 children born between 1996 and 2016 in six U.S. health care systems and Ontario, Canada, until the earliest of cancer or benign-tumor diagnosis, death, end of health care coverage, an age of 21 years, or December 31, 2017. Radiation doses to active bone marrow from medical imaging were quantified. Associations between hematologic cancers and cumulative radiation exposure (vs. no exposure), with a lag of 6 months, were estimated with the use of continuous-time hazards models.

Results: During 35,715,325 person-years of follow-up (mean, 10.1 years per person), 2961 hematologic cancers were diagnosed, primarily lymphoid cancers (2349 [79.3%]), myeloid cancers or acute leukemia (460 [15.5%]), and histiocytic- or dendritic-cell cancers (129 [4.4%]). The mean (±SD) exposure among children exposed to at least 1 mGy was 14.0±23.1 mGy overall (for comparison, 13.7 mGy was the exposure from one computed tomographic [CT] scan of the head) and 24.5±36.4 mGy among children with hematologic cancer. Cancer risk increased with cumulative dose, with a relative risk (vs. no exposure) of 1.41 (95% confidence interval [CI], 1.11 to 1.78) for 1 to less than 5 mGy, 1.82 (95% CI, 1.33 to 2.43) for 15 to less than 20 mGy, and 3.59 (95% CI, 2.22 to 5.44) for 50 to less than 100 mGy. The cumulative radiation dose to bone marrow was associated with an increased risk of all hematologic cancers (excess relative risk per 100 mGy, 2.54 [95% CI, 1.70 to 3.51; P<0.001]; relative risk for 30 vs. 0 mGy, 1.76 [95% CI, 1.51 to 2.05]) and most tumor subtypes. The excess cumulative incidence of hematologic cancers by 21 years of age among children exposed to at least 30 mGy (mean, 57 mGy) was 25.6 per 10,000. We estimated that, in our cohort, 10.1% (95% CI, 5.8 to 14.2) of hematologic cancers may have been attributable to radiation exposure from medical imaging, with higher risks from the higher-dose medical-imaging tests such as CT.

Conclusions: Our study suggests an association between exposure to radiation from medical imaging and a small but significantly increased risk of hematologic cancer among children and adolescents. (Funded by the National Cancer Institute and others.).

Figure 1.

Relative risks for all hematologic malignancies by cumulative bone marrow dose (in mGy). Dots show estimated relative risks by categories of cumulative dose (see Table S4). Vertical bars show 95% confidence intervals (CI). The solid line represents the fitted dose-response from the linear model (excess relative risk (ERR)=2.54 per 100 mGy exposure). The shaded area represents the upper and lower CIs for the dose-response (95% CI for ERR=1.70 to 3.52). The dashed horizontal line represents the reference value (RR=1.0). The vertical lines at the bottom of the figure show the cumulative doses for children with a hematologic malignancy. Two children with doses above 200 mGy are not included.

Figure 2

Relative risk of hematologic malignancy for a dose of 30 mGy (vs. no exposure) by time since exposure (modeled as a continuous variable) with separate lines by age at exposure (modeled as a categorical variable). Results from other dose exposures shown in Table S5. Results from other dose exposures and confidence intervals shown in Table S5.

Figure 3

Cumulative incidence of hematologic malignancy by attained age and active bone marrow dose, among children without Down’s syndrome. The cumulative incidence and 95% CI are shown for age 21 years. Shaded blue area represents the 95% confidence interval for the no exposure (0 mGy) group. Confidence bands for other groups are omitted for readability.