www.thelancet.com Published online June 7, 2012 DOI:10.1016/S0140-6736(12)60815-0 1
June 7, 2012
Institute of Health and Society
(M S Pearce PhD, J A Salotti PhD,
N L Howe MSc) and Northern
Institute of Cancer Research
(Sir A W Craft MD), Newcastle
University, Sir James Spence
Institute, Royal Victoria
Infi rmary, Newcastle upon
Tyne, UK; Radiation
Epidemiology Branch, Division
of Cancer Epidemiology and
Genetics, National Cancer
Institute, Bethesda, MD, USA
(M P Little PhD, C Lee PhD,
C M Ronckers PhD,
P Rajaraman PhD,
A B de González DPhil);
Great Ormond Street Hospital
for Children NHS Trust,
London, UK (K McHugh FRCR);
Department of Nuclear
Engineering, Kyung Hee
South Korea (K P Kim PhD);
Dutch Childhood Oncology
Group—Longterm eff ects after
(DOCG-LATER), The Hague,
Netherlands (C M Ronckers);
and Departments of Medicine
and Paediatrics, Population
Cancer Research Program,
Dalhousie University, Halifax,
Nova Scotia, Canada
(L Parker PhD)
Dr Mark S Pearce, Institute of
Health and Society, Newcastle
University, Sir James Spence
Institute, Royal Victoria Infi rmary,
Newcastle upon Tyne NE1 4LP, UK
Radiation exposure from CT scans in childhood and
subsequent risk of leukaemia and brain tumours:
a retrospective cohort study
Mark S Pearce, Jane A Salotti, Mark P Little, Kieran McHugh, Choonsik Lee, Kwang Pyo Kim, Nicola L Howe, Cecile M Ronckers, Preetha Rajaraman,
Sir Alan W Craft, Louise Parker, Amy Berrington de González
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 fi rst
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 fi rst CT and for brain tumours 5 years after the fi rst 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
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 fi rst 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 benefi ts 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.
CT imaging is a valuable diagnostic technique, and new
clinical applications continue to be identifi ed. As a result,
the rates of CT use have increased rapidly in the USA and
elsewhere, particularly in the past 10 years.1 Although the
immediate benefi t to the individual patient can be sub-
stantial, the relatively high radiation doses associated
with CT compared with conventional radiog raphy have
raised health concerns.2–8 Potential increases in future
cancer risk, attributable to the rapid expansion in CT use
have been estimated with risk projection models, which
are derived mainly from studies of survivors of the atomic
bombs in Japan.3,6,8 These studies have been criticised
because of concerns about how applicable the fi ndings
from this group are to the relatively low doses of radiation
exposure from CT scans and to non-Japanese populations.
Some investigators claim that there are no risks, or even
benefi cial eff ects, associated with low-dose radiation.9 No
direct studies of cancer risk in patients who have
undergone CT scans have been undertaken to date.
We did a study to directly assess the question of
whether cancer risks are increased after CT scans in
childhood and young adulthood. Here we assess the risks
of leukaemia and brain tumours because they are the
endpoints of greatest concern as the red bone marrow
and brain are highly radiosensitive tissues, especially in
childhood.10 Furthermore, these tissues are also some of
the most highly exposed from childhood CT scans,11 and
leukaemias and brain tumours are the most common
Patients and study design
In our observational retrospective cohort study, we
included patients without previous malignant disease
who were fi rst examined with CT between 1985 and
www.thelancet.com Published online June 7, 2012 DOI:10.1016/S0140-6736(12)60815-0
2002 when they were younger than 22 years of age.
Patients were scanned at hospitals within 81 National
Health Service (NHS) regional services in Great Britain
(England, Wales, and Scotland). We assembled the cohort
with historical data from electronic radiology information
systems (RIS) from the participating hospitals or, for a
small number of patients in fi ve hospitals, from paper or
fi lm records. Retrieved data included date of birth, details
of the CT examinations, sex, post code, and body parts
scanned. We used the patient’s identifi ers to identify
patients having scans in more than one hospital.
This study was approved by the Newcastle and North
Tyneside Local Research Ethics Committee (Newcastle
upon Tyne, UK) and by the UK National Information
Governance Board, exempting the study from requiring
individual patient’s consent.
Linkage with the NHS Central Registry (NHSCR)
provided cancer incidence, mortality and loss-to-follow-up
data (eg, notifi ed emigrations) from Jan 1, 1985, to
Dec 31, 2008. The NHSCR holds compu terised records
of everyone registered with an NHS general practitioner
in Great Britain (most residents). It is continuously
updated with births, deaths, marriages, name changes,
and movements of patients, and records cancer
incidence from the regional cancer registries. We
excluded patients from the cohort who had an exit date
of less than 2 years in the case of leukaemia or less than
5 years for brain tumours after the fi rst scan to reduce
the possibility of inclusion of patients who had CT scans
because a cancer was suspected. We also excluded
patients who could not be traced by NHSCR, and those
who had missing information or inaccurate information
on the date of CT scan.
The appendix shows details of the morphology
codes used to defi ne leukaemias. We examined four
non-mutually exclusive leukaemia subgroups, which
were acute lymphoblastic leukaemia, acute myeloid
leukaemia, myelodysplastic syndromes, and leukaemia
excluding myelodysplastic syndrome. We defi ned
malig nant and benign brain tumours with WHO’s
Inter national Classifi cation of Diseases for Oncology,
3rd edition topographic codes for meninges, brain,
olfactory, and cranial nerves, and other parts of the CNS
(spinal tumours were excluded). We examined two
subgroups: glioma and meningioma plus schwan noma
CT scans deliver very non-uniform radiation doses
across the body. Therefore, we assessed the risk of
leukaemia and brain tumours in relation to estimated
radiation absorbed doses in the appropriate organ (red
bone marrow or brain), which were estimated for each
type of scan without knowledge of case status. The
absorbed dose from a CT scan depends on factors
including age, sex, examination type, and year of scan.
Data for the machine settings that also infl uence dose,
such as milliampere seconds and peak kilovoltage, were
not available for every individual patient from the
electronic databases during the study period. Therefore,
we obtained typical machine settings for CT in young
people from UK-wide surveys undertaken in 1989 and
2003.11,12 We combined these data with those from a series
of hybrid computational human phantoms13 and Monte
Carlo radiation transport techniques to estimate absorbed
doses to the red bone marrow and brain for reference
males and females for integer years of age between 0 and
22 years.14,15 Table 1 shows estimated red bone marrow
and brain doses from diff erent CT examinations by age
and sex after 2001. Dose estimates before 2001 were
generally 2–3 times higher than were those after this date
because age-specifi c technical settings were rarely used
in earlier years.12
We assessed potential associations between radiation
dose and cancer outcomes with Poisson relative risk
models fi tted by maximum likelihood (see appendix). To
avoid inclusion of CT scans related to cancer diagnosis
we began accrual of person-time for leukaemia inci-
dence 2 years after the fi rst CT scan and for brain
tumours 5 years after the fi rst CT scan. We continued
Male patients Female patients
Brain dose (mGy)Red bone marrow
Brain dose (mGy) Red bone marrow
Age at brain CT
Age at chest CT
Age at abdominal CT
Age at extremity CT
Table 1: Estimated radiation doses to the brain and red bone marrow from one CT scan, by scan type, sex,
and age at scan, as used in this study for scans after 2001
See Online for appendix
www.thelancet.com Published online June 7, 2012 DOI:10.1016/S0140-6736(12)60815-0 3
accrual of data until date of fi rst cancer diagnosis or the
earliest of death, loss-to-follow-up, or Dec 31, 2008.
Because it typically takes at least 2 years for radiation-
related leukaemia to develop and 5 years for a solid
cancer to develop,16 doses were lagged by 2 years for
leukaemia and by 5 years for brain tumours. Application
of the exclusions and lag periods are described in the
appendix. We did sensitivity analyses in which the
exclusion and lag periods were increased to 10 years for
brain tumours, the follow-up period for leukaemia was
decreased from 2008 to 2004, and the age at end of
follow-up was restricted to patients younger than
25 years for leukaemia and younger than 28 years for
brain tumours. We did signifi cance tests on the basis of
the likelihood-ratio test. Unless otherwise stated, we
based CIs on the profi le likelihood.17 When the statistical
software failed to produce a convergent profi le likelihood
bound we used the Wald-based (Fisher information-
based) confi dence bound. All p values are two-sided and
p<0·05 was regarded as signifi cant. We did all statistical
analyses with the DATAB and AMFIT modules of the
Role of the funding source
The sponsors of the study had no role in study design,
data collection, data analysis, data interpretation, or
writing of the report. MSP and ABdG had full access to
all the data in the study and had fi nal responsibility for
the decision to submit for publication.
After exclusion of 33 372 patients who could not be traced
by NHSCR because of incomplete names or dates of
birth in the RIS databases (and 960 non-UK resident
Age at fi rst exposure, years
Attained age, years
Years since fi rst exposure
Number of CT scans
1 266 110
1 239 170
1 720 984
1 188 207
Person-year data in the leukaemia group do not sum to the overall number
because of rounding. *Follow-up starting 2 years after fi rst CT scan. †Follow-up
starting 5 years after fi rst CT scan.
Table 2: Cases of leukaemia and brain tumours and person-years for
patients in the assessed cohort
Figure: Relative risk of leukaemia and brain tumours in relation to estimated
radiation doses to the red bone marrow and brain from CT scans
(A) Leukaemia and (B) brain tumours. Dotted line is the fi tted linear
dose-response model (excess relative risk per mGy). Bars show 95% CIs.
0 1020 30 40 506070
Red bone marrow dose (mGy)
0 50 100150 200250300350400
Brain dose (mGy)
www.thelancet.com Published online June 7, 2012 DOI:10.1016/S0140-6736(12)60815-0
patients) and those who were ineligible for follow-up
because the exit date occurred less than 2 years in the
case of leukaemia analyses or 5 years for brain tumours
after the fi rst scan (or when information, such as date of
scan, was missing or obviously inaccurate), we included
178 604 individuals in the leukaemia analyses and
176 587 in the brain tumour analyses (table 2).
We included 283 919 CT scans in the analysis of
leukaemia risk, of which 64% (182 337 scans) were of the
head. The next most common CT scan types were of the
abdomen and/or pelvis (9%, 25 695 scans) and chest CT
(7%, 18 910 scans; appendix). The distribution of scan
types was very similar for patients in the brain tumour
analysis, but the total number of scans was slightly
smaller than in the leukaemia analysis because of the
longer exclusion period (279 824 scans). Table 2 lists the
distri butions of cases and overall person-years, by sex,
age at fi rst scan, attained age, years since fi rst scan, and
the number of scans.
The risk of leukaemia was positively associated with
estimated doses delivered by CT scans to the red bone
marrow (p=0·0097), as was the risk of brain tumours
associated with estimated doses delivered by CT scans to
the brain tissue (p<0·0001; fi gure).
Compared with doses of less than 5 mGy, the relative
risk (RR) of leukaemia for patients who received doses
of at least 30 mGy (mean dose in this group was
51·13 mGy) was 3·18 (95% CI 1·46–6·94; appendix).
Compared with doses of less than 5 mGy, the RR of
brain tumours for patients receiving 50–74 mGy
(mean dose 60·42 mGy) was 2·82 (1·33–6·03; fi gure,
appendix), and for patients receiving 50 mGy or more
(mean dose 104·16 mGy) the brain tumour RR is 3·32
(95% CI 1·84–6·42; appendix). To put this into context,
after 2001, 5–10 head CTs in children younger than
15 years result in the accumulation of about 50 mGy red
bone marrow dose and 2–3 head CTs results in about a
60 mGy cumulative brain dose (table 1).
We noted positive associations between CT scans and
cancer subgroups of gliomas (p=0·0033), schwannoma
and meningiomas (p=0·0195), acute lymphoblastic
leukaemia (p=0·0053), and myelodysplastic syndromes
(p=0·0032), but not acute myeloid leukaemia (p=0·2653)
or leukaemia excluding myelodysplastic syndromes
(p=0·1436; table 3). For leu kaemia, the dose response did
not vary between age at exposure, time since exposure,
sex, or any other co variates examined (table 4). However,
for brain tumours there was signifi cant heterogeneity
(p=0·0003) in estimated RR (ERR) across categories of
age at exposure, with ERR increasing with increasing age.
We noted little evidence of non-linearity of the
dose-response, using either linear-quadratic or linear-
exponential forms of departure from linearity (leukaemia
exponential p=0·2672 and quadratic p=0·4683, brain
tumour exponential p=0·9203 and quadratic p=0·8993).
In sensitivity analyses in which all scans 10 years before
brain tumour diagnosis were excluded, the magnitude of
the dose-responses was increased rather than decreased
as might be expected if the association was driven by bias
from CT scans related to the diagnosis (appendix). When
Cases ERR per mGy (95% CI) p value (test for
Red bone marrow dose
All leukaemia, including myelodysplastic syndromes
Acute lymphoblastic leukaemia
Acute myeloid leukaemia
Leukaemia excluding myelodysplastic syndromes
Schwannoma and meningioma
0·036 (0·005 to 0·120)
1·719* (>0 to 17·73†)
0·021 (–0·042† to 0·155)
6·098* (>0 to 145·4†)
0·019 (–0·012† to 0·079)
0·023 (0·010 to 0·049)
0·019 (0·003 to 0·070)
0·033 (0·002 to 0·439)
ERR=excess relative risk. *Iteratively reweighted least-squares algorithm failed to converge, so parameter estimates
might be unreliable. †Calculated using Wald-based CI.
Table 3: Excess relative risk per mGy for cancer subtypes in relation to organ-specifi c radiation doses
received from CT scans
ERR per mGyp value ERR per mGy p value
Years since fi rst exposure
Years since last exposure
Number of CT scans
Age at exposure (years)‡
Years since exposure‡
ERR=excess relative risk. ··=not applicable (follow-up started at 5 years).
*Includes individual of unknown sex. †Aliased parameter, set to zero.
Table 4: Excess relative risk per mGy for leukaemia and brain tumours,
by various personal characteristics
www.thelancet.com Published online June 7, 2012 DOI:10.1016/S0140-6736(12)60815-0 5
follow-up for leu kaemia was restricted to 2004, the dose-
response also increased, which was as expected given the
short latency period for leukaemia and early peak in excess
risk reported in previous studies.10,16 To assess whether the
missing exposure data after age 22 years resulted in
underestimation of doses and hence over estimation of the
relative risks, we restricted follow-up to individuals
younger than 28 years for brain tumours and individuals
younger than 25 years for leukaemia, but this did not
change the dose-response estimates.
In this retrospective cohort study, we show signifi cant
associations between the estimated radiation doses
provided by CT scans to red bone marrow and brain and
subsequent incidence of leukaemia and brain tumours.
Assuming typical doses for scans done after 2001 in
children aged younger than 15 years, cumulative ionising
radiation doses from 2–3 head CTs (ie, ~60 mGy) could
almost triple the risk of brain tumours and 5–10 head
CTs (~50 mGy) could triple the risk of leukaemia.
Although no previous cohort studies have assessed the
risk of cancer after CT, several studies have reported
signifi cantly increased cancer risks after radiation
exposure in the range received from multiple CT scans
(100 mGy).19 Such studies include those of survivors of
the atomic bombs in Japan,20 nuclear workers,21 and
patients who received tens of diagnostic radiographs.22 A
few case-control studies have also assessed cancer risks
from CT scans on the basis of self-reported history of
diagnostic radiograph exposures.23,24 These studies might
be subject to recall bias whereby patients are more likely
to recall previous medical radiation exposures than are
unaff ected controls, and also high levels of reporting
error. We avoided such bias by taking a cohort approach
and assessing more accurate exposure histories from
medical records (panel).
In terms of the quantitative estimates of the risk, our
primary comparison for leukaemias and brain tumours
is with the Life Span Study20 of Japanese atomic bomb
survivors, which is the most comprehensive study of
cancer after radiation exposure currently available.10,16
The dose-response for leukaemia following childhood
exposure and similar follow-up time (<15 years after
exposure) in the Life Span Study was 0·045 per mSv
(95% CI 0·016–0·188; appendix) which was much the
same as our estimate (ERR of 0·036 per mGy
[0·005–0·120]; 1 mSv=1 mGy). For brain tumours, our
result (ERR 0·023 per mGy [0·010–0·049]) was about
four times higher than was the Life Span Study estimate
(0·0061 per mSv [0·0001–0·0639] <20 years after
exposure; appendix), but the CIs are wide and over-
lapped. We had reduced power to examine risks by
subtype of neoplasm, age, or time since exposure
compared with the Life Span Study, partly because of the
more restricted ranges of length of follow-up and age at
exposure. The increased risks noted in our study
compared with the Life Span Study might be because
existing tumours in some patients were not detected at
the time of their fi rst CT. The relatively low-energy
x-radiation from CT scans might also be about twice as
biologically eff ective per unit dose as the mainly high-
energy γ-rays that were the predominant exposure source
from the atomic bombings in Hiroshima and Nagasaki.16
Our large study sample was collected from a wide
range of hospitals in Great Britain. Because most
medical attendances at hospitals in Great Britain,
particularly for the age group in this study, are in public,
free-to-access, NHS hospitals, the sample is probably
representative of the childhood and young adult
population in the country as a whole who undergo CT.
Ascertainment of cancer diagnoses by NHSCR is
estimated to be 97%25 and therefore there is a low
likelihood of losses to follow-up. Patients who were
excluded because linkage to their records was not
possible had similar characteristics to those who were
linked and thus should not have biased conclusions.
Because we assessed children and young adults, our
results are directly applicable to a highly radiosensitive
section of the population,10 although whether the results
can be generalised to adulthood CT scans has not been
established. Moreover, because most (>80%) of the
population assessed was white, whether the results are
generalisable to other ethnic groups is unknown.
CT is often used as a diagnostic technique when a solid
cancer is suspected. However, information about the
reasons for CTs and other clinical variables were not
available for this study. Instead, we excluded all scans
undertaken in the 2 years before a leukaemia diagnosis
and 5 years before a brain tumour diagnosis. Young
Panel: Research in context
We searched PubMed and Medline databases without date or language restriction for
articles with the search terms “computed tomography”, “ionizing radiation”, “cancer”,
“radiation-induced neoplasms”, “case-control”, and “prospective”. We reviewed reports
from scientifi c committees such as the International Commission on Radiological
Protection (ICRP), United Nations Scientifi c Committee on the Eff ects of Atomic
Radiation (UNSCEAR), and Biological Eff ects of Ionizing Radiations (BEIR), and also a
broader range of publications and reports covering medical imaging and radiation
exposure. We checked references from selected publications for relevance to this study
including comments, correspondence, and editorials. Exposure to ionising radiation is an
established risk factor for leukaemia and brain tumours.10,16 Although CT has important
clinical uses, concerns exist about the potential cancer risks from the associated ionising
radiation, particularly for children. Rates of CT use have been rising rapidly in the
Increases that we noted in incidence rates of leukaemia and brain tumours after
childhood exposure to CT scans are unlikely to be due to confounding factors. The
evaluated risks per unit dose were consistent with those derived from recent analyses of
cohorts exposed to higher average radiation doses and dose rates. The current study
supports the extrapolation of such risk models to doses from CT scans.
www.thelancet.com Published online June 7, 2012 DOI:10.1016/S0140-6736(12)60815-0
patients with leukaemia are unlikely to have a CT because
of their disease,26 but we still used a cautious approach of
applying an exclusion period. By contrast, patients with
brain tumours will probably have a number of CT
examinations during the diagnostic period, hence the
longer exclusion period. Nevertheless, we noted much
the same results in sensitivity analyses in which all scans
in the 10 years before a brain tumour diagnosis were
excluded. The absence of data for other exposures, such
as radiographs, is unlikely to have introduced a major
bias because the doses from these scans are typically ten-
times smaller than those for CT scans. However, we
cannot rule out this bias and the increased dose response
noted for brain tumours compared with the survivors of
the atomic bombs in Japan is also a possible indication of
some residual bias despite the long exclusion period.
Previous dose estimates for CT typically provided
eff ective dose rather than organ doses and were restricted
in terms of the ages covered. In this study, a series of
phantoms with a higher age resolution from newborn to
adult was used for both males and females. We also used
more realistic anatomy and bone marrow dosimetry
models compared with previous computational phan toms.
These advanced features allow more accurate and valid
estimates of organ-specifi c doses. Despite these advanced
methods, uncertainties exist for our dose estimates.
However, such uncertainties are likely to be mainly
Berksonian (resulting from applying group-averaged
estimates), and thus would not be expected to bias the dose
response.27 Collection of detailed scan parameter data for
individual patients was not possible. Instead, we used
average CT machine settings from two national surveys
and assumed that no technical adjust ment was made for
paediatric patients before 2001.5
Absolute excess risk estimates are necessary to put the
risks into perspective with the benefi ts of the scans. Good
evidence from the long-term study of the atomic bomb
survivors in Japan suggests that cancer risk persists
indefi nitely after radiation exposure and most cancer
types are inducible by radiation.10,16 At present, we only
have suffi cient case numbers to assess brain tumours
and leukaemia, and the maximum age of patients at the
end of follow-up is 45 years, with a minimum age of
6 years and maximum follow-up time of 23 years.
Provisional estimates of excess absolute risk for the end
of follow-up at about 10 years after exposure suggest that,
of 10 000 people between the ages of 0–20 years receiving
10 mGy from a CT scan, there would be about 0·83
(95% CI 0·12–2·77) excess leukaemia cases and 0·32
(0·14–0·69) excess brain tumours (appendix). Applying
the dose estimates for one head CT scan before the age of
10 years (table 1) this estimate would translate into
approximately one excess case of leukaemia and one
excess brain tumour per 10 000 patients. Increased
follow-up and analysis of other cancer types is needed to
identify the lifetime excess cancer risk associated with
CT scans. Some evidence28 suggests that doses in the
range delivered by several CT scans might increase the
risk of cardiovascular disease. Investigating this feature
would require not only the same long-term follow-up
required for adulthood cancer outcomes, but also a new
approach to obtain cardiovascular incidence data, which
is not currently recorded on a registry rather than reliance
on mortality data.
Various studies have estimated the potential lifetime
excess cancer risks from CT scans from risk projection
models, which are largely based on risk models from
studies of survivors of the atomic bombs in Japan.
Because our relative risk estimates are broadly consistent
with the results from the Life Span Study, this study
provides additional direct support for the existing life-
time absolute cancer risk projections for paediatric
patients.3,7,8,29 The most recent risk projections8 suggest
that, for children with normal life expectancy, the lifetime
excess risk of any incident cancer for a head CT scan
(with typical dose levels used in the USA) is about one
cancer per 1000 head CT scans for young children
(<5 years), decreasing to about one cancer per 2000 scans
for exposure at age 15 years. For an abdominal or pelvic
CT scan, the lifetime risks for children are one cancer
per 500 scans irrespective of age at exposure. These
absolute excess lifetime cancer risks (to age 100 years) are
very small compared with the lifetime risk of developing
cancer in the general population, which is about one in
three, and are also likely to be small compared with the
benefi ts of the scan, providing it is clinically justifi ed.1
We estimated doses for each scan that every patient
received, obtained outcome data for the patients, and
provided direct evidence that doses at the level children
and young adults can receive from CT are associated
with increased risks of leukaemia and brain tumours.
The dose-response relation that we noted and relative
risks of more than 2 for an exposure that is an established
carcinogen at higher dose-levels10,16 is evidence that this
relation is unlikely to be entirely due to confounding
factors. With the increasing use of CT worldwide,
particularly within this young population,8 knowledge of
the risks based on empirical data will be crucial to assess
safety in relation to the benefi ts that CT provides.
Frequent calls have been made to decrease doses,
following the as low as reasonably achievable (ALARA)
principle, and only scan when justifi ed as in the current
image gently campaign.30 In the UK, the Ionising
Radiation (Medical Exposure) Regulations mean that a
CT scan should only be done when clinically justifi ed,
which might explain the low levels of CT use in the UK
compared with other countries that do not have such
regulations. The immediate benefi ts of CT outweigh the
long-term risks in many settings31 and because of CT’s
diagnostic accuracy and speed of scanning, notably
removing the need for anaesthesia and sedation in
young patients, it will remain in widespread practice for
the foreseeable future. Further refi nements to allow
reduction in CT doses should be a priority, not only for
www.thelancet.com Published online June 7, 2012 DOI:10.1016/S0140-6736(12)60815-0 7
the radiology community but also for manufacturers.
Alternative diagnostic procedures that do not involve
ionising radiation exposure, such as ultrasound and
MRI might be appropriate in some clinical settings.
LP and AWC conceived the study. MSP, LP, KM, AWC, CMR, ABdG
organised funding or continued intramural funding. MSP, LP, AWC,
and CMR designed the study. MSP, JAS, NLH, and PR did the data
collection and processing. CL, KPK, ABdG, KM, and MSP did the
dosimetry analysis. MPL, ABdG, and MSP did the statistical analysis.
MSP and ABdG wrote the report, which was revised and approved by all
authors. MSP and ABdG take overall responsibility for the integrity of
the study. LP and ABdG were joint senior authors.
Confl icts of interest
We declare that we have no confl icts of interest.
This study was supported by contract NO2-CP-75501 from the US
National Cancer Institute and by the Radiation Research Programme of
the UK Department of Health (RRX119). We thank the North of England
Children’s Cancer Research Fund for their continued support of
paediatric cancer epidemiology studies at Newcastle University
(Newcastle upon Tyne, UK); the staff in radiology departments across
Great Britain who contributed data; Richard Hardy, Katharine Kirton,
and Wenhua Metcalf from Newcastle University; Jeremy Miller
(Information Management Services, Rockville, MD, USA); and
Martha Linet and Lindsay Morton from the National Cancer Institute
(Bethesda, MD, USA) for their assistance. Elaine Ron, who was one of
the original investigators for this study, died of cancer on Nov 20, 2010.
We greatly appreciate her contributions, support, and devotion to this
study and to the fi eld of radiation epidemiology.
1 Pearce MS. Patterns in paediatric CT use: an international and
epidemiological perspective. J Med Imaging Radiat Oncol 2011;
2 Rehani MM, Berry M. Radiation doses in computed tomography.
The increasing doses of radiation need to be controlled. BMJ 2000;
3 Brenner DJ, Elliston CD, Hall EJ, Berdon W. Estimated risks of
radiation-induced fatal cancer from paediatric CT.
AJR Am J Roentgenol 2001; 176: 289–96.
4 Parker L. Computed tomography scanning in children: radiation
risks. Pediatr Hematol Oncol 2001; 18: 307–08.
5 Paterson A, Frush DP, Donnelly LF. Helical CT of the body:
are settings adjusted for paediatric patients? AJR Am J Roentgenol
2001; 176: 297–301.
6 Brenner DJ, Elliston CD. Estimated radiation risks potentially
associated with full-body screening. Radiology 2004; 232: 735–38.
7 Brenner DJ, Hall EJ. Computed tomography—an increasing source
of radiation exposure. N Engl J Med 2007; 357: 2277–84.
8 Berrington de González A, Mahesh M, Kim KP, et al. Projected
cancer risks from computed tomographic scans performed in the
United States in 2007. Arch Int Med 2009; 169: 2071–77.
9 Tubiana M, Feinendegen LE, Yang C, Kaminski JM. The linear
no-threshold relationship is inconsistent with radiation biology and
experimental data. Radiology 2009; 251: 13–22.
10 United Nations Scientifi c Committee on the Eff ects of Atomic
Radiation. UNSCEAR 2008 Report to the General Assembly.
New York: United Nations, 2010.
11 National Radiological Protection Board. Survey of CT practice in
the UK. Chilton, UK: National Radiological Protection Board,
12 Shrimpton P, Hillier M, Lewis M, Dunn M. Doses from computed
tomography (CT) examinations in the UK-2003 (NRPB-W67).
Chilton, UK: National Radiological Protection Board, 2005.
13 Lee C, Lodwick D, Hurtado J, Pafundi D, Williams JL, Bolch WE.
The UF family of reference hybrid phantoms for computational
radiation dosimetry. Phys Med Biol 2010; 55: 339–63.
14 Lee C, Kim K, Long D, et al. Organ doses for reference adult male
and female undergoing computed tomography estimated by Monte
Carlo simulations. Med Phys 2011; 38: 1196–206.
15 Kim KP, Berrington de González A, Pearce MS, et al. Development
of a database of organ doses for pediatric and young adult CT scans
in the United Kingdom. Radiat Prot Dosim 2012; published online
Jan 6. DOI:10.1093/rpd/ncr429.
16 Committee to Assess Health Risks from Exposure to Low Levels of
Ionizing Radiation. Health Risks from exposure to low levels of
ionizing radiation. BEIR VII Phase 2. Washington DC: The National
Academies Press, 2006.
17 McCullagh P, Nelder JA. Generalized linear models, 2nd edn.
Monographs on statistics and applied probability 37. Boca Raton, FL:
Chapman and Hall/CRC, 1989: 1–526.
18 Preston DL, Lubin JH, Pierce DA, McConney ME. Epicure:
user’s guide. Seattle, WA: Hirosoft International Corporation, 1993.
19 Einstein AJ. Eff ects of radiation exposure from cardiac imaging:
how good are the data? J Am Coll Cardiol 2012; 59: 553–65.
20 Preston DL, Kusumi S, Tomonaga M, et al. Cancer incidence in
atomic bomb survivors. Part III: leukemia, lymphoma and multiple
myeloma. Radiat Res 1994; 137: S68–97.
21 Cardis E, Vrijheid M, Blettner M, et al. Risk of cancer after low
doses of ionising radiation: retrospective cohort study in
15 countries. BMJ 2005; 331: 77–80.
22 Boice JD Jr, Preston D, Davis FG, Monson RR. Frequent chest x-ray
fl uoroscopy and breast cancer incidence among tuberculosis
patients in Massachusetts. Radiat Res 1991; 125: 214–22.
23 Davis F, Il’yasova D, Rankin K, McCarthy B, Bigner DD. Medical
diagnostic radiation exposures and risk of gliomas. Radiat Res 2011;
24 Blettner M, Schlehofer B, Samkange-Zeeb F, Berg G, Schlaefer K,
Schüz J. Medical exposure to ionising radiation and the risk of
brain tumours: Interphone study group, Germany. Eur J Cancer
2007; 43: 1990–98.
25 Offi ce for National Statistics. Summary quality report for cancer
registration statistics. Information Paper, Offi ce for National
26 Ahmed BA, Connolly BL, Shroff P, et al. Cumulative eff ective doses
from radiologic procedures for pediatric oncology patients.
Pediatrics 2010; 126: e851–58.
27 Carroll RJ, Ruppert D, Stefanski LA, Crainiceanu CM.
Measurement error in nonlinear models. A modern perspective.
Boca Raton, FL, Chapman and Hall/CRC, 2006: 1–488.
28 Little MP, Azizova TV, Bazyka D, et al. Systematic review and
meta-analysis of circulatory disease from exposure to low-level
ionizing radiation and estimates of potential population mortality
risks. Env Health Perspect (in press).
29 Chodick G, Ronckers CM, Shalev V, Ron E. Excess lifetime cancer
mortality risk attributable to radiation exposure from computed
tomography examinations in children. Isr Med Assoc J 2007; 9: 584–87.
30 Strauss KJ, Goske MJ, Kaste SC, et al. Image gently: ten steps you
can take to optimize image quality and lower CT dose for pediatric
patients. AJR Am J Roentgenol 2010; 194: 868–73.
31 Budoff M. Cardiac CT: benefi ts outweigh the risks.
J Cardiovasc Comput Tomogr 2011; 5: 275–76.
www.thelancet.com Published online June 7, 2012 DOI:10.1016/S0140-6736(12)60897-6 1
Beyond the bombs: cancer risks of low-dose medical radiation
More than a decade ago, Brenner and colleagues’
landmark report1 suggested that radiation doses
attributed to paediatric CT scans would lead to a
signifi cant number of excess cancer deaths. The risk
estimates produced for paediatric CT in that study,1 and
subsequent estimates for other medical exposures,2
were derived from risk projection models based on
studies of survivors of the atomic bombs in Japan.3,4
Many diff erences exist between a CT scan and exposure
to an atomic bomb—for example, CT scans are usually
focused on a particular part of the body, whereas atomic
bomb exposures aff ected the whole body. Investigators
took these diff erences into account insofar as possible in
the models used to estimate CT scan risks, but were the
predictions correct? Was there a small yet real cancer risk
associated with CT scans?
Many medical practitioners suggested that the
evidence for cancer risk associated with CT scanning
was speculation. A position paper5 from the American
Association of Physicists in Medicine stated that: “Risks
of medical imaging at eff ective doses below 50 mSv for
single procedures or 100 mSv for multiple procedures
over short time periods are too low to be detectable
and may be non-existent”. Indeed, no epidemiological
study had been published that convincingly showed
increased incidence of cancers associated with low-
dose radiation from medical imaging during childhood
or adulthood. Others argued that the risk estimates
were based on the best available science at the time.
Now, a study by Mark Pearce and colleagues6 in The
Lancet enters the fray. The authors investigated a cohort
of 178 604 children without cancer who underwent
CT between 1985 and 2002 in various hospitals in
England, Scotland, and Wales. They used state-of-the-art
dosimetric methodology to estimate radiation doses to
individual organs, and identifi ed subsequent cancers via
linkage to the National Health Service Central Registry.
To avoid confounding the data with CT scans undertaken
for cancer diagnosis, the group excluded leukaemias
occurring within 2 years of the scan and brain tumours
occurring within 5 years, lag periods during which
radiation-related cancer is not thought to occur.
This initial analysis of the cohort6 was restricted to
assessments of the risk of leukaemia and brain cancer,
with a typical follow-up of about 10 years after exposure
and maximum follow-up of 23 years. During this
follow-up period, Pearce and colleagues noted increases
in leukaemia incidence in children with cumulative
bone marrow doses from CT of at least 30 mGy (here
1 mGy=1 mSv), and signifi cant increases in brain
tumour incidence in children with brain doses of at least
50 mGy. Assuming typical doses used since 2001, the
authors suggest that 2–3 head CTs could triple children’s
(<15 years old) risk of brain cancer and that 5–10 head
CTs could triple their risk of leukaemia. Their fi ndings
suggest an increased (but statistically compatible) risk
of brain cancer attributable to radiation per unit dose
compared with data for atomic bomb survivors, and
much the same leukaemia risk.
At least 12 other groups are studying or planning to
study national cohorts of children (table). Large cohort
studies of Australians and Canadians are expected to
report fi ndings in 1–2 years, whereas the Epidemiological
Study to Quantify Risks for Paediatric Computerized
Tomography and to Optimise Doses (EPI-CT) is expected
to report a pooled analysis of data from nine European
cohorts, including an extended version of the British
cohort,6 in 2016. Future analyses of British children are
expected to assess cancer risks from other solid tumours
Size of exposed
Age at exposure
Start date of
EPI-CT (pooled European)
1 045 000§
4 105 000
Data for European studies adapted from reference 7. Additional data provided by G Chodick (Maccabi Healthcare
Services), A Kesminiene (International Agency for Research on Cancer), V Kirsh (Cancer Care Ontario), J Mathews
(University of Melbourne), and I Thierry-Chef (International Agency for Research on Cancer). *0–10 years from 2007.
†Including the extended cohort. ‡Pearce and colleagues’ study.6 §Estimated size.
Table: Cohort studies of CT exposure and cancer incidence
June 7, 2012
Comment Download full-text
www.thelancet.com Published online June 7, 2012 DOI:10.1016/S0140-6736(12)60897-6
based on longer follow-up and the expanded cohort.
These studies will provide a more robust evidence base,
which will inform our understanding of cancer induced
by low-dose radiation.
What implications does this study6 have for clinical
practice and policy? It should reduce the debates about
whether risks from CT are real, but the specialty has
anyway changed strikingly in the past decade, even
while the risk debate continued. New CT scanners all
now have dose-reductions options, and there is far more
awareness among practitioners about the need to justify
and optimise CT doses—an awareness that will surely be
bolstered by Pearce and colleagues’ study.6
Justifi cation of any CT scan is important because good
evidence suggests that 20–50% of such examinations
could be replaced with another type of imaging or not
done at all.8 For individual patients, justifi cation should
take account of all available information, including
details of the proposed procedure and alternative
expected radiation dose and associated degree of risk,
information about previous or expected procedures,
and patients’ preferences.9 Justifi cation is a shared
responsibility between referring and performing
health-care professionals,9 and is facilitated by the
“three As”: awareness, appropriateness, and audit—
awareness by knowledgeable providers who assist the
patient in balancing the immediate benefi ts of medical
radiation with its downstream radiation risk, use of
appropriateness guidelines to ensure that those patients
referred for radiological examinations need them, and
post-hoc audit of imaging use against agreed standards
of good practice.8
Optimisation incorporates keeping radiation exposure
as low as reasonably achievable (ALARA) for every study.
Various modality and procedure-specifi c techniques
are available, although they are not always used. For
example, in paediatric CT these techniques include
selecting scan parameters such as the radiographic
tube current and voltage to refl ect the size of the
child, personalising protocols on the basis of referral
indication, limiting the area scanned, and scanning only
once.10 However, the wide range of dose indices reported
for the same CT procedures11 underscores the extensive
eff orts still needed to ensure that radiation exposure is
optimised for every patient.
Pearce and colleagues confi rm that CT scans almost
certainly produce a small cancer risk. Use of CT scans
continues to rise, generally with good clinical reasons,
so we must redouble our eff orts to justify and optimise
every CT scan.
Andrew J Einstein
Division of Cardiology, Department of Medicine, and Department
of Radiology, Columbia University Medical Center, New York,
NY 10032, USA
AJE is supported by US National Heart, Lung, and Blood Institute R01 HL109711,
a Victoria and Esther Aboodi Assistant Professorship, and the Louis V Gerstner Jr
Scholars Program; has received research support from GE Healthcare and
Spectrum Dynamics; and has been a consultant for Kyowa Hakko Kirin Pharma
and the International Atomic Energy Agency.
1 Brenner D, Elliston C, Hall E, Berdon W. Estimated risks of
radiation-induced fatal cancer from pediatric CT. AJR Am J Roentgenol
2001; 176: 289–96.
Einstein AJ, Henzlova MJ, Rajagopalan S. Estimating risk of cancer
associated with radiation exposure from 64-slice computed tomography
coronary angiography. JAMA 2007; 298: 317–23.
Preston DL, Ron E, Tokuoka S, et al. Solid cancer incidence in atomic bomb
survivors: 1958–1998. Radiat Res 2007; 168: 1–64.
Einstein AJ. Eff ects of radiation exposure from cardiac imaging: how good
are the data? J Am Coll Cardiol 2012; 59: 553–65.
American Association of Physicists in Medicine. AAPM position statement
on radiation risks from medical imaging procedures: 12/13/2011. http://
(accessed May 29, 2012).
Pearce MS, Salotti JA, Little MP, et al. Radiation exposure from CT scans in
childhood and subsequent risk of leukaemia and brain tumours:
a retrospective cohort study. Lancet 2012; published online June 7.
International Agency for Research on Cancer. EPI-CT International pediatric
CT scan study. http://epi-ct.iarc.fr/index.php (accessed May 29, 2012).
Malone J, Guleria R, Craven C, et al. Justifi cation of diagnostic medical
exposures: some practical issues. Report of an International Atomic Energy
Agency Consultation. Br J Radiol 2012; 85: 523–38.
International Commission on Radiological Protection. The 2007
recommendations of the International Commission on Radiological
Protection. ICRP Publication 103. Ann ICRP 2007; 37: 1–332.
10 Strauss KJ, Goske MJ, Kaste SC, et al. Image gently: ten steps you can take to
optimize image quality and lower CT dose for pediatric patients.
AJR Am J Roentgenol 2010; 194: 868–73.
11 Smith-Bindman R, Lipson J, Marcus R, et al. Radiation dose associated with
common computed tomography examinations and the associated lifetime
attributable risk of cancer. Arch Intern Med 2009; 169: 2078–86.