Cancer risks following low-dose radiation fromCT scans in childhood
New insights into effects of age at exposureand attained ageJohn Mathews
CSRP 2016

Acknowledgments
Particular thanks are due to the 15 co-authors of our BMJ
publication.
Data access and linkage was facilitated by• Health & Ageing, Medicare Australia• Australian Institute of Health and Welfare• State and Territory governments and cancer registrars
This report includes valuable contributions from Darren
Wraith (now at the Queensland University of Technology),
Marissa Bartlett (Queensland Health), Anna Forsythe, andZoe Brady2Themes for the talk
1. CT (computed tomography) X-ray scans are important in medicaldiagnosis;
2. However, radiation doses from CT scans are typically greater than
the annual dose of background radiation;
3. Cancer risks are increased following diagnostic CT scan radiation
before the age of 20 years.
4. Is this due to bias from reverse causation?
5. Why are the risk estimates for low-dose radiation from CT scans
greater than those estimated in the LSS of atomic survivors?
6. What does this mean for low dose radiation effects fromenvironmental contamination, as at Fukushima?

3

Per capita CT usage varies by Country
400350JAPANNo. CT scans / 1000 persons

300250USA

200150

AUSTRALIA

1005001985

UK
1990

1995

2000

2005

2010

4

Context and significance ofCT exposed cohorts•

Theoretical papers by Brenner and others from 2000
predicted an increased risk following childhood CT based on
results from the Life Span Study (LSS) of atomic survivors.

•Pearce et al (2012) used UK data to show an actual
increase in brain cancer & leukaemia following childhood CT
Our Australian study (Mathews et al, 2013) showed actual
increases in brain cancer, leukaemia, and other solidcancers. Our study had:
• About 4 times the exposure of the UK study• About 4-5 times as much low dose exposure as LSS•• Longer follow-up of medically-exposed cohorts
will soon answer the “low-dose” radiationquestion.
5Cancer after CT scans - Study design

Exposure

Outcome
OutcomeRecords of CT scans fundedby Medicare for all persons
aged 0-19 years in 19852005

First diagnoses of cancer
more than 12 months afterCT exposure

Data linkage in high security unitof the Australian Institute of Health &Welfare

Analysis of de-identified data at theUniversity of Melbourne
6

A large study
CT exposed

Non-exposed

680,211

10,259,469• Exposure more than 12
months prior to any cancer
diagnosis• No Medicare record of any
CT scan• When aged 0-19 years• When aged 0-19 years• In period 1985-2005• In period 1985-2005• Follow-up to 31/12/2007• Follow-up to 31/12/2007
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Leukaemias in our cohort

0.00002.00004.00006.00008Age-specific incidence of leukaemias in the cohort

01020
Attained age (years)

Lymphoid leukaemia

3040

Myeloid leukaemia
8Brain cancer in our cohort

0.00001.00002.00003.00004Age-specific incidence of brain cancer (C710-719)

01020

Attained age (years)

3040
9Cohort follow-up details
Characteristic(at one year lag)Exposedpersons

Unexposedpersons

Number of person
years of follow-up

6 486 548

177 191 342

Mean length offollow-up (years)

9.5

17.3

Number ofcancers

3150

57 524
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So what did we find?
1 year lag

5 year lag

10 year lag

Observed cancers in
exposed

3,150

2,3651,405

Expected cancers
in exposed

2,542

1,963

1,196

Incidence rate ratio(IRR) & 95 % CI

1.24
(1.20,1.29)

1.21(1.16,1.26)

1.18(1.11,1.24)
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Cancer risk by number of CT scans(All cancers & all exposures)

1.2( χ2 for trend: 131.4 ,p<0.0001).
If unexposed persons areexcluded the trend remains
significant.8

1.6
1.4

increased by 0.16 (95% CI
0.13 to 0.19) for each
additional CT scan,calculated after
stratification for age, sex,
and year of birth

11.8

The incidence rate ratio0123

Number of CT scans per individual( χ2 for trend: 5.79, p =0.02).
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Different measures of CT risk
MeasureAverage risk More extreme risk

Excess relativerisk

16% increase per 200% per CT afterCT
exposure at an earlyage

Absolute
increase

1 extra cancer
per 2000 scans

Attributable risk 14 % per CT
for a person withcancer after
exposure

Will continue toincrease over time
67% for a person withbrain cancer after
exposure at a youngage
13Understanding Attributable Risk
An example
If a child is exposed to a CT head scan before the ageof 5 years, then in the years that follow, the averagerate of brain cancer is 3 times as great as for“unexposed”.
We are interested in the attributable risk - probability
that the cancer was caused by exposure. This iscalculated as:
A.R. = Excess rate in exposed/Overall rate in exposed= (3-1)/3 = 2/3 = 67%
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Cancers after head CT – 5 year lag
Type of cancer

No. exposedcancers

Incidence rate
ratio (IRR)

IRR 95%
confidence interval

Brain cancer

123

2.03(1.69-2.43)

Soft tissue461.55(1.15-2.08)

Thyroid130

1.36(1.14-1.62)

Leukaemia

100

1.25(1.02-1.53)

Other solid536

1.12(1.03-1.22)

All cancers1532

1.21(1.15-1.27)
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What about “reverse causation”?
Cancers at the shortest lag periods following CT
scans are almost certainly due to “reversecausation”, as when symptoms of cancer or apre-cancerous condition prompt the CT scan.
It was for this reason that in our BMJ paper wechose to exclude cancers occurring at a lag ofless than 12 months after exposure.
Can we be more precise about cancers due toreverse causation at different lag periods?
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What about reverse causation?

-9-8-7-6-5

Rate of cancer diagnosis by time since CT exposure

051015Lag period in years between CT scan and cancer diagnosis
Cancer incidence in CT exposed
Cancer incidence in matched unexposed cohort

20

Fitted values

17Reverse causation is over by 2 yrs

0.2.4.6.8

1

Estimated proportion of cancers attributable to CTby time since exposure02468Lag in years between CT exposure and cancer diagnosis
Mean estimate
95% confidence interval

10Extreme estimate
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Comparing Risk Estimates
Exposure details

Typicaldose (mSv)

Excess relative risk per Sv
Leukemia

Solid cancers

Reference

1049 (33-67)

45 (30-62)

Doll & Wakeford (29)Life Span Study

100-25045 (16-188)

3 (2-6)

Table 9 in
Mathews et al. (8)CT (UK study)

636 (5-120)-Pearce et al. (9)CT (Australia)

639 (14-70)

27 (17-37)

Mathews et al. (8)Background5-1070 (10-130)-Kendall(30)Life Span Study

100-250

3.2 (1.9-4.6)

0.6 (0.5-0.7)

BEIR VII (2)Radiation workers

15

3 (1.2-5.2)

Prenatal X-rays

Childhood exposures(0-19 years)

Adult exposures

19

Leuraud et al. (31)0.97 (0.3-1.8)
0.58 (-0.1-1.4)*

Cardis et al. (32)19How do we explain the increased
risk of solid cancers after CT?

Is it due to:
1. Reverse causation
2. A greater causal effect in the early years
after exposures at young ages
3. A greater effect, per unit of dose, at lowdoses (i.e. a non-linear dose response)20

Risk is much greater in early years
after exposure at young ages

210.25 0.5

Excess relative risk

4 6

Excess relative risk of solid cancer ( log scale)by age at CT exposure and age at diagnosis

01020Age at cancer diagnosis

Exposed at age 2
Exposed at age 6Exposed at age 10
Exposed at age 143040

Exposed at age 4Exposed at age 8Exposed at age 1221

ERR/Gy is less at higher doses

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Dose response may be non-linear
Theoretical prediction of ERR (excess relative risk) as a function of radiation dose2.5Excess relative risk

2
1.5
1

ERR = a.dose0.33
0.5

00

0.2

0.4

0.6

0.8

11.2

1.4

1.6

1.8

2

Dose in Gray
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SUMMARY 1•••••

There are no compelling reasons to doubt thefindings from the Australian CT study.
The Australian CT cohort was exposed to more lowdose radiation (<100 mGy) than the LSS.
The excess cancers at more than 12-24 months
after CT are mostly caused by CT-scan radiation
Risks of leukaemia following CT scan radiation areconsistent with risks from LSS of atomic survivors.
Excess risks of solid cancers per unit of dose are
greater after CT scans than in LSS survivors
presumably because of lower doses, and because
early cancers were missed in the LSS.
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SUMMARY 2• Excess cancers in the early years after radiation
exposure at young ages probably occur insusceptible persons• Susceptibility is likely due to inherited or somaticallymutated cancer genes• The dose response curve for radiation is steeper atlower doses and at short lags because of:•Genetic susceptibility and stochastic selection••

Homeostatic mechanisms such as the bystander response
Cell killing at higher doses• Important implications for radiation protection!
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