Relationship between paediatric CT scans and subsequent risk of leukaemia and brain tumours: assessment of the impact of underlying conditions.

BACKGROUND: We previously reported evidence of a dose-response relationship between ionising-radiation exposure from paediatric computed tomography (CT) scans and the risk of leukaemia and brain tumours in a large UK cohort. Underlying unreported conditions could have introduced bias into these findings. METHODS: We collected and reviewed additional clinical information from radiology information systems (RIS) databases, underlying cause of death and pathology reports. We conducted sensitivity analyses excluding participants with cancer-predisposing conditions or previous unreported cancers and compared the dose-response analyses with our original results. RESULTS: We obtained information from the RIS and death certificates for about 40% of the cohort (n∼180 000) and found cancer-predisposing conditions in 4 out of 74 leukaemia/myelodysplastic syndrome (MDS) cases and 13 out of 135 brain tumour cases. As these conditions were unrelated to CT exposure, exclusion of these participants did not alter the dose-response relationships. We found evidence of previous unreported cancers in 2 leukaemia/MDS cases, 7 brain tumour cases and 232 in non-cases. These previous cancers were related to increased number of CTs. Exclusion of these cancers reduced the excess relative risk per mGy by 15% from 0.036 to 0.033 for leukaemia/MDS (P-trend=0.02) and by 30% from 0.023 to 0.016 (P-trend<0.0001) for brain tumours. When we included pathology reports we had additional clinical information for 90% of the cases. Additional exclusions from these reports further reduced the risk estimates, but this sensitivity analysis may have underestimated risks as reports were only available for cases. CONCLUSIONS: Although there was evidence of some bias in our original risk estimates, re-analysis of the cohort with additional clinical data still showed an increased cancer risk after low-dose radiation exposure from CT scans in young patients.

Trends and patterns in the use of computed tomography in children and young adults in Catalonia - results from the EPI-CT study.

BACKGROUND: Although there are undeniable diagnostic benefits of CT scanning, its increasing use in paediatric radiology has become a topic of concern regarding patient radioprotection. OBJECTIVE: To assess the rate of CT scanning in Catalonia, Spain, among patients younger than 21 years old at the scan time. MATERIALS AND METHODS: This is a sub-study of a larger international cohort study (EPI-CT, the International pediatric CT scan study). Data were retrieved from the radiological information systems (RIS) of eight hospitals in Catalonia since the implementation of digital registration (between 1991 and 2010) until 2013. RESULTS: The absolute number of CT scans annually increased 4.5% between 1991 and 2013, which was less accentuated when RIS was implemented in most hospitals. Because the population attending the hospitals also increased, however, the rate of scanned patients changed little (8.3 to 9.4 per 1,000 population). The proportions of patients with more than one CT and more than three CTs showed a 1.51- and 2.7-fold increase, respectively, over the 23 years. CONCLUSION: Gradual increases in numbers of examinations and scanned patients were observed in Catalonia, potentially explained by new CT scanning indications and increases in the availability of scanners, the number of scans per patient and the size of the attended population.

Langerhans cell histiocytosis in children with congenital anomalies: a population-based record linkage study.

BACKGROUND: The etiology of Langerhans cell histiocytosis (LCH), a rare cancer-like disorder of the immune system, is largely unknown although a genetic component has been suggested based on familial cases, and reports of chromosome instability and genetic mutation. Associations between various cancers and congenital anomalies have been reported and although congenital anomalies have been noted in children with LCH only one study to date has reported their frequency. An association between congenital anomalies and LCH may suggest a common etiological pathway, in particular, a genetic pathway. METHODS: Data from two coterminous registries in the same geographic region were used. All cases of LCH on the Northern Region Young Persons Malignant Disease Register diagnosed between 1985 and 2010 were cross-matched with live-born cases of congenital anomaly registered by the Northern Congenital Abnormality Survey. RESULTS: A total of 819,890 children and young people were born during 1985 to 2008. Of these, 13,799 (1.7%) had a congenital anomaly and 39 (0.005%) were diagnosed with LCH. Three LCH cases were identified among those with congenital anomalies, all three of whom had congenital heart disease. The relative risk of LCH for those with a congenital anomaly, compared with those without, was 4.87 (95% confidence interval, 1.50-15.81; p = 0.03). CONCLUSION: LCH was associated with congenital anomaly in a small but statistically significant number of patients, raising the possibility of a common genetic pathway in some cases.

EPI-CT: design, challenges and epidemiological methods of an international study on cancer risk after paediatric and young adult CT.

Computed tomography (CT) has great clinical utility and its usage has increased dramatically over the years. Concerns have been raised, however, about health impacts of ionising radiation exposure from CTs, particularly in children, who have a higher risk for some radiation induced diseases. Direct estimation of the health impact of these exposures is needed, but the conduct of epidemiological studies of paediatric CT populations poses a number of challenges which, if not addressed, could invalidate the results. The aim of the present paper is to review the main challenges of a study on the health impact of paediatric CTs and how the protocol of the European collaborative study EPI-CT, coordinated by the International Agency for Research on Cancer (IARC), is designed to address them. The study, based on a common protocol, is being conducted in Belgium, Denmark, France, Germany, the Netherlands, Norway, Spain, Sweden and the United Kingdom and it has recruited over one million patients suitable for long-term prospective follow-up. Cohort accrual relies on records of participating hospital radiology departments. Basic demographic information and technical data on the CT procedure needed to estimate organ doses are being abstracted and passive follow-up is being conducted by linkage to population-based cancer and mortality registries. The main issues which may affect the validity of study results include missing doses from other radiological procedures, missing CTs, confounding by CT indication and socioeconomic status and dose reconstruction. Sub-studies are underway to evaluate their potential impact. By focusing on the issues which challenge the validity of risk estimates from CT exposures, EPI-CT will be able to address limitations of previous CT studies, thus providing reliable estimates of risk of solid tumours and leukaemia from paediatric CT exposures and scientific bases for the optimisation of paediatric CT protocols and patient protection.

Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours: a retrospective cohort study.

BACKGROUND: Although CT scans are very useful clinically, potential cancer risks exist from associated ionising radiation, in particular for children who are more radiosensitive than adults. We aimed to assess the excess risk of leukaemia and brain tumours after CT scans in a cohort of children and young adults. METHODS: In our retrospective cohort study, we included patients without previous cancer diagnoses who were first examined with CT in National Health Service (NHS) centres in England, Wales, or Scotland (Great Britain) between 1985 and 2002, when they were younger than 22 years of age. We obtained data for cancer incidence, mortality, and loss to follow-up from the NHS Central Registry from Jan 1, 1985, to Dec 31, 2008. We estimated absorbed brain and red bone marrow doses per CT scan in mGy and assessed excess incidence of leukaemia and brain tumours cancer with Poisson relative risk models. To avoid inclusion of CT scans related to cancer diagnosis, follow-up for leukaemia began 2 years after the first CT and for brain tumours 5 years after the first CT. FINDINGS: During follow-up, 74 of 178,604 patients were diagnosed with leukaemia and 135 of 176,587 patients were diagnosed with brain tumours. We noted a positive association between radiation dose from CT scans and leukaemia (excess relative risk [ERR] per mGy 0·036, 95% CI 0·005-0·120; p=0·0097) and brain tumours (0·023, 0·010-0·049; p<0·0001). Compared with patients who received a dose of less than 5 mGy, the relative risk of leukaemia for patients who received a cumulative dose of at least 30 mGy (mean dose 51·13 mGy) was 3·18 (95% CI 1·46-6·94) and the relative risk of brain cancer for patients who received a cumulative dose of 50-74 mGy (mean dose 60·42 mGy) was 2·82 (1·33-6·03). INTERPRETATION: Use of CT scans in children to deliver cumulative doses of about 50 mGy might almost triple the risk of leukaemia and doses of about 60 mGy might triple the risk of brain cancer. Because these cancers are relatively rare, the cumulative absolute risks are small: in the 10 years after the first scan for patients younger than 10 years, one excess case of leukaemia and one excess case of brain tumour per 10,000 head CT scans is estimated to occur. Nevertheless, although clinical benefits should outweigh the small absolute risks, radiation doses from CT scans ought to be kept as low as possible and alternative procedures, which do not involve ionising radiation, should be considered if appropriate. FUNDING: US National Cancer Institute and UK Department of Health.

Socio-economic variation in CT scanning in Northern England, 1990-2002.

BACKGROUND: Socio-economic status is known to influence health throughout life. In childhood, studies have shown increased injury rates in more deprived settings. Socio-economic status may therefore be related to rates of certain medical procedures, such as computed tomography (CT) scans. This study aimed to assess socio-economic variation among young people having CT scans in Northern England between 1990 and 2002 inclusive. METHODS: Electronic data were obtained from Radiology Information Systems of all nine National Health Service hospital Trusts in the region. CT scan data, including sex, date of scan, age at scan, number and type of scans were assessed in relation to quintiles of Townsend deprivation scores, obtained from linkage of postcodes with census data, using χ2 tests and Spearman rank correlations. RESULTS: During the study period, 39,676 scans were recorded on 21,089 patients, with 38,007 scans and 19,485 patients (11344 male and 8132 female) linkable to Townsend scores. The overall distributions of both scans and patients by quintile of Townsend deprivation scores were significantly different to the distributions of Townsend scores from the census wards included in the study (p < 0.0001). There was a significant association between type of scan and deprivation quintile (p < 0.0001), primarily due to the higher proportions of head scans in the three most deprived quintiles, and slightly higher proportions of chest scans and abdomen and pelvis scans in the least deprived groups. There was also a significant association (p < 0.0001) between the patient's age at the time of the CT scan and Townsend deprivation quintiles, with slightly increasing proportions of younger children with increasing deprivation. A similar association with age (p < 0.0001) was seen when restricting the data to include only the first scan of each patient. The number of scans per patient was also associated with Townsend deprivation quintiles (p = 0.014). CONCLUSIONS: Social inequalities exist in the numbers of young people undergoing CT scans with those from deprived areas more likely to do so. This may reflect the rates of injuries in these individuals and implies that certain groups within the population may receive higher radiation doses than others due to medical procedures.

CT scans in young people in Northern England: trends and patterns 1993-2002.

BACKGROUND: Although CT can be greatly beneficial, its relatively high radiation doses have caused public health concerns. OBJECTIVE: To assess patterns in CT usage among patients aged less than 22 years in Northern England during the period 1993-2002. MATERIALS AND METHODS: Electronic data were obtained from radiology information systems of all nine National Health Service trusts in the region. RESULTS: A total of 38,681 scans had been performed in 20,483 patients aged less than 22 years. The number of CT examinations rose, with the steepest increase between 1997 and 2000. The number of patients scanned per year increased less dramatically, with 2.24/1,000 population aged less than 22 years having one scan or more in 1993 compared to 3.54/1,000 in 2002. This reflects an increase in the median number of scans per patient, which rose from 1 in 1993 to 2 by 1999. More than 70% of CT examinations were of the head, with the number of head examinations varying with time and patient age. CONCLUSION: The frequency of CT scans in this population more than doubled during the study period. This is partly, but not wholly, explained by an increase in the number of scans per patient.

Reduction in radiation doses from paediatric CT scans in Great Britain.

OBJECTIVE: Although CT scans provide great medical benefits, concerns have been raised about the magnitude of possible associated cancer risk, particularly in children who are more sensitive to radiation than adults. Unnecessary high doses during CT examinations can also be delivered to children, if the scan parameters are not adjusted for patient age and size. We conducted the first survey to directly assess the trends in CT scan parameters and doses for paediatric CT scans performed in Great Britain between 1978 and 2008. METHODS: We retrieved 1073 CT film sets from 36 hospitals. The patients were 0-19 years old, and CT scans were conducted between 1978 and 2008. We extracted scan parameters from each film including tube current-time product [milliampere seconds (mAs)], tube potential [peak kilovoltage (kVp)] and manufacturer and model of the CT scanner. We estimated the mean mAs for head and trunk (chest and abdomen/pelvis) scans, according to patient age (0-4, 5-9, 10-14 and 15-19 years) and scan year (<1990, 1990-1994, 1995-1999 and ≥2000), and then derived the volumetric CT dose index and estimated organ doses. RESULTS: For head CT scans, mean mAs decreased by about 47% on average from before 1990 to after 2000, with the decrease starting around 1990. The mean mAs for head CTs did not vary with age before 1990, whereas slightly lower mAs values were used for younger patients after 1990. Similar declines in mAs were observed for trunk CTs: a 46% decline on an average from before 1990 to after 2000. Although mean mAs for trunk CTs did not vary with age before 1990, the value varied markedly by age, from 63 mAs for age 0-4 years compared with 315 mAs for those aged >15 years after 2000. No material changes in kVp were found. Estimated brain-absorbed dose from head CT scans decreased from 62 mGy before 1990 to approximately 30 mGy after 2000. For chest CT scans, the lung dose to children aged 0-4 years decreased from 28 mGy before 1990 to 4 mGy after 2000. CONCLUSION: We found that mAs for head and trunk CTs was approximately halved starting around 1990, and age-specific mAs was generally used for paediatric scans after this date. These changes will have substantially reduced the radiation exposure to children from CT scans in Great Britain. ADVANCES IN KNOWLEDGE: The study shows that mAs and major organ doses for paediatric CT scans in Great Britain began to decrease around 1990.

Increasing use of radioiodine in young people with thyrotoxicosis in Great Britain.

OBJECTIVE: Radioiodine (RI) is an important therapeutic option in young patients with thyrotoxicosis. We wanted to determine whether RI is being used more frequently in this age group. DESIGN: National survey of Great Britain (England, Wales and Scotland). METHODS: Sixty-one medical physics departments were asked to provide the age and number of patients with thyrotoxicosis <21 years treated with RI (1990-2008). Information on the total number of RI treatments for thyrotoxicosis was also collected. RESULTS: Forty-three departments (70%), with representation from 21 of the 25 most populous areas of Great Britain, provided data on 69,258 treatments. The number of treatments recorded on patients <21 years during this period was 560 (0.9%). The frequency of treatments in young people as a percentage of the total increased from 0.2% in 1990 to 1.5% in 2008 (P<0.001). When the 18 centres submitting at least 17 years of data were analysed, a similar pattern was observed. The maximum number of young people treated was greatest in 2008 (62) with a fall in the youngest age at which RI was administered from 18 years (1990) to 11 years (2008). CONCLUSIONS: A rising proportion of patients with thyrotoxicosis receiving RI are in those <21 years. This is largely due to an increase in the number of young people treated with a reduction in the minimum age at RI administration. We suspect that European clinicians are becoming more comfortable with RI treatment in young people with thyrotoxicosis, although a changing incidence is a potential contributing factor.

CT Scans in Young People in Great Britain: Temporal and Descriptive Patterns, 1993-2002.

Background. Although using computed tomography (CT) can be greatly beneficial, the associated relatively high radiation doses have led to growing concerns in relation to potential associations with risk of future cancer. Very little has been published regarding the trends of CT use in young people. Therefore, our objective was to assess temporal and other patterns in CT usage among patients aged under 22 years in Great Britain from 1993 to 2002. Methods. Electronic data were obtained from the Radiology Information Systems of 81 hospital trusts within Great Britain. All included patients were aged under 22 years and examined using CT between 1993 and 2002, with accessible radiology records. Results. The number of CT examinations doubled over the study period. While increases in numbers of recorded examinations were seen across all age groups, the greatest increases were in the older patients, most notably those aged 15-19 years of age. Sixty percent of CT examinations were of the head, with the percentages varying with calendar year and patient age. Conclusions. In contrast to previous data from the North of England, the doubling of CT use was not accompanied by an increase in numbers of multiple examinations to the same individual.