Paediatric computed tomography and subsequent risk of leukaemia, intracranial malignancy and lymphoma: a nationwide population-based cohort study

Abstract

Red bone marrow and brain tissue are highly radiosensitive in children. We investigate the relationship between childhood computed tomography (ct) exposure and leukaemia, intracranial malignancy and lymphoma. All participants in the study were aged less than 16 years. A total of 1,479 patients in the leukaemia group, 976 patients in the intracranial malignancy group and 301 patients in the lymphoma group were extracted from the Catastrophic Illness Certificate Database in Taiwan as the disease group. In total, 126,677 subjects were extracted from the Longitudinal Health Insurance Database 2010 of the Taiwan National Health Insurance Research Database as the non-disease group. The odds ratios (ORs) and 95% confidence intervals (CIs) for childhood CT exposure and times of childhood CT were estimated. childhood ct exposure was correlated to the intracranial malignancy group in both oneyear (oR = 1.95, 95% CI 1.40-2.71, p < 0.001) and two-year (OR = 1.56, 95% CI 1.04-2.33, p = 0.031) exclusion periods. the time of childhood ct was also correlated to intracranial malignancy in both oneyear (oR = 1.69, 95% CI 1.34-2.13, p < 0.001) and two-year (OR = 1.55, 95% CI 1.17-2.04, p = 0.002) exclusion periods. the results indicated that childhood ct exposure was correlated with an increased risk of future intracranial malignancy. Computed tomography (CT) is widely used in modern hospitals and provides accurate, timely information. A previous study estimated that 29,000 cases of cancer and 14,500 deaths in the general population annually in the U.S. may be induced by CT exposure 1. An official report from Australia noted that an irradiation dose of over 20 mSv for the general population was associated with a greater than one in 1000 risk of developing fatal cancers, non-fatal cancers and serious hereditary diseases 2,3. Recently, many studies have found that ionizing radiation exposure in children may cause serious complications, including malignancy 4-7. Several studies demonstrated that red bone marrow and brain tissue were highly radiosensitive, especially during childhood 8-10. A recent report pointed out that the increase in the incidence of all cancers in CT-exposed individuals aged 0-19 years was 9.38 per 100,000 person years in Australia 5. A study from the United Kingdom reported that the relative risk (RR) for individuals aged 0-22 years who received bone marrow radiation doses greater than 30 mGy was 3.18, and the risk for patients who received brain radiation doses greater than 50 mGy was 2.82 4. Leukaemia, intracranial malignancy and lymphoma are the most common malignancies in children in Taiwan 11. Many studies have pointed out a relationship between leukaemia, intracranial malignancy and ionizing radiation exposure 1,9,12-16. Therefore, we aim to investigate the relationships between childhood CT exposure and these three major malignancies using cohort data from the Taiwan National Health Insurance research database (NHIRD).

Childhood cancer risks estimates following CT scans: an update of the French CT cohort study

“…However, concerns have been raised about possible cancer risks, particularly after exposure to CT in childhood, due to the greater radiation sensitivity of children for at least 25% of cancer sites [3] and to their longer life expectancy allowing to develop radiation associated late health effects. Significant increased risks of central nervous system (CNS) tumors associated with CT scans exposure during childhood have been reported in the United Kingdom (UK), Australia, Taiwan, Germany and the Netherlands [4][5][6][7][8][9].…”

Cancer risks among studies of medical diagnostic radiation exposure in early life without quantitative estimates of dose

“…Milne et al (Milne et al, 2014) also evaluated lag periods between 6 months and 5 years in relation to all radiological procedures, but little difference in brain tumour risk was observed. Reverse causation and confounding by indication are general problems in studies of diagnostic radiation exposure; only a few of the studies of other types of postnatal exposure assembled here deal with this by use of lag periods (Ager et al, 1965;Baaken et al, 2019;Bartley et al, 2010;Graham et al, 1966;Howe et al, 1989;Meinert et al, 1999;Preston-Martin et al, 1982;Rajaraman et al, 2011;Schuz et al, 2001;Shu et al, 2002), even to the limited extent that is attempted by Tettamanti et al (Tettamanti et al, 2017), Hong et al (Hong et al, 2019), Li et al (Li et al, 2020), Bailey et al (Bailey et al, 2010) and Milne et al (Milne et al, 2014) (see Table 2). Hence, one cannot discount the possibility that the relatively modest increases we have seen for postnatal exposures may largely result from such biases, and in this respect it is of interest that in the CT scan study of Hong et al (Hong et al, 2019), of the many different types of cancer investigated, the RR (with a lag of 2 years) was <1.0 only for lymphoid leukaemia while the RR estimates were >1.0 for all other types of cancer, some significantly so (e.g., digestive and respiratory cancers and NHL) and others not.…”

“…Both issues are usually dealt with in the analysis by employing lag and exclusion periods, and a simulation study suggests that this should be enough to eliminate bias from this cause (Little et al, 2022a). However, for solid cancers it is common to use larger values of lag and exclusion than the period of two years used in the studies of Tettamanti et al (Tettamanti et al, 2017), Hong et al (Hong et al, 2019) and Li et al (Li et al, 2020), or the period of 6 months employed in the studies of Bailey et al (Bailey et al, 2010) and Milne et al (Milne et al, 2014), that are considered here.…”

“…So for analysis of kidney cancer mortality we still employed the data of Spengler et al (Spengler et al, 1983), although for the all cancer and leukaemia analysis we employed the findings for cancer incidence of McLaughlin et al (McLaughlin et al, 1993). The CT scan study of Huang et al (Huang et al, 2014) has been largely superseded, with a slightly larger age range, and only a single year of coverage outside that included in the later study of Li et al (Li et al, 2020); both studies are listed in Table 2, but only the later study was used in the meta-analysis.…”

“…Again, the tendency for risks to be raised is apparent in Figure 2 showing risks from the studies for the three main cancer endpoints (leukaemia, brain/CNS tumours, lymphoma), and raised risks are more evident in earlier studies. Among the more striking of the reported risks are those for leukaemia in the study of patients exposed to diagnostic X-rays and fluoroscopy by Polhemus et al (Polhemus and Koch, 1959), for brain tumours and dental X-rays in the studies of Preston-Martin et al (Preston-Martin et al, 1980;Preston-Martin et al, 1982) for brain tumours and skull X-rays in the Canadian study of Howe et al (Howe et al, 1989), non-Hodgkin lymphoma (NHL) in the Israel cardiac catheterisation study of Modan et al (Modan et al, 2000), and in relation to various cancer endpoints and CT scans in the studies of Hong et al (Hong et al, 2019) and Li et al (Li et al, 2020).…”