Thyroid dose estimation for epidemiologic studies André Bouville (NCI, retired) and Vladimir...

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Thyroid dose estimation for epidemiologic studies

André Bouville (NCI, retired) and Vladimir Drozdovitch (NCI)

Workshop on Radiation and Thyroid CancerTokyo, Japan, 22 February 2014

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Outline

• Background information• Principles of dose reconstruction• Examples of studies and dose estimates• Concluding remarks

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Background information

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Analytic epidemiologic studies

• Requirement:– Unbiased individual dose estimates for a large

number of subjects• Examples of studies:

– Chernobyl: UA-US and BY-US studies among children

– Chernobyl: UA-US in utero study– Fallout: Marshall Islands study

Exposure Pathways

Pasture-cow-milk pathway (131I)

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Principles of thyroid dose reconstruction in a large

environmental study

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Six Principles of Dose Reconstruction

● Perform person-based measurements.

● Administer interviews.

● Conduct environmental measurements.

● Obtain realistic estimates of dose.

● Validate the dose estimates.

● Estimate the uncertainties attached to the dose estimates.

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Principle #1: person-based measurements

● Objective: perform as many person-based measurements as possible.

● Rationale: dose estimates are much less uncertain when they are based on:

person-based measurements , than on

environmental radiation measurements, or on

data on activities released into the environment.

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Thyroid dose is propor-tional to area under the curve

0

5

10

15

20

25

30

0 20 40 6020 40 60

Time after the accident(days)

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1 ac

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Thyroid Dose Estimation (multiple measurements)

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Thyroid dose is propor-tional to area under the curve

0

5

10

15

20

25

30

0 20 40 60

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Curve derived from 131I models plus data from questionnaire

Thyroid Dose Estimation (usual case)

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Principle #2: personal interviews

● Objective: identify the conditions of radioiodine intake as early as possible.

● Rationale:

- the internal dose estimates are very sensitive to the conditions of radioiodine intake. It is important to clarify if inhalation occurred in a single day or over several days and if ingestion was a significant mode of exposure,

- because of memory loss, the personal interviews should be performed soon after the accident.

Personal interview

• Inhalation: residence history (including number of hours spent indoors) during the first two months following the accident

• Ingestion: consumption rates and origin (market or own garden) of water, milk, and leafy vegetables

• Countermeasures: sheltering, evacuation, and/or stable iodine administration, if conducted

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Questions to interviewees(in case of exposure to 131I)

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Principle #3: environmental measurements

● Objective: development of a model predicting the variation with time of the intake rate of 131I.

● Rationale:

- environmental measurements (131I in air, water, soil, vegetation, foodstuffs + 137Cs in air and soil) are the best data that could supplement the person-based measurements,

- when environmental measurements are not available, estimates of released activities, combined with models of atmospheric transport, have to be used.

137Cs deposition map (Chernobyl accident)

< 3 7 k B q m -2

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Principle #4: realistic dose estimationPrinciple #5: validation of dose estimatesPrinciple #6: estimation of uncertainties

● Objectives: obtain realistic (unbiased) estimates of dose for all subjects of the epidemiologic study; make sure that the estimated doses are reasonably reliable; and quantify the uncertainties

● Rationale: the dose estimates have to be credible and arguments must exist to defend their

credibility.

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Examples of studies and dose estimates

Chornobyl Accident – 26 April 1986

The most severeaccident thatever occurred inthe nuclearpower industry.

NCI Chornobyl thyroid study

• Cohort study of about 25,000 subjects (13,000 Ukrainians and 12,000 Belarusians) exposed as children.

• Lived in contaminated areas of Ukraine and Belarus.

• All subjects had a person-based measurement (131I activity in the thyroid).

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Distribution of thyroid dose estimates

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Thyroid dose

interval (Gy)

Number of subjects

Ukraine Belarus

N % N %<0.2 6,729 51.0 5,407 46.1

0.2 – 0.49 2,829 21.4 2,867 24.4

0.5 – 1.99 2,735 20.7 2,812 24.0

2.0 – 9.99 838 6.3 612 5.2

≥10 73 0.6 34 0.3

All 13,204 100 11,732 100Mean (Gy) 0.65 0.58

Distribution of GSD according to dose (Ukrainian cohort)

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GSD interval

N %Mean

thyroid dose (Gy)

≥3 217 1.6 0.017

2.0 – 2.99 294 2.2 0.26

1.5 – 1.99 4,711 35.7 0.68

1.26 – 1.49 7,982 60.5 0.66

In-utero study of thyroid cancer in Ukraine

Number of subjects: 2,584, including three groups:

• Subgroup L1-C: 720 subjects. Their mothers:– lived in a contaminated area in April-June 1986; and – had a person-based measurement (131I activity in thyroid).

• Subgroup L2-C: 776 subjects. Their mothers:– lived in a contaminated area in April-June 1986; and – did not have a person-based measurement, but a number of women from

the same settlement of residence had such a measurement.

• Subgroup L1-NC: 1088 subjects. Their mothers:– lived in a non-contaminated area in April-June 1986; and – did not have a person-bases measurement, and no other woman from the

same settlement of residence had such a measurement.

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Estimation of doses for the 2,584 in-utero subjects

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Direct thyroid measurements

(for 720 MOTHERS)

Subjects of contaminated

areas

1496

Subjects of “non-contaminated”

areas

1088

Individual Questionnaires

History of pregnancy

Behavior:• milk consumption• leafy vegetables

• relocation

Sets of personal information

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Results of in utero thyroid dose calculation

Thyroid dose, mGy

Contaminated areas(L1-C + L2-C)

“Non-contaminated” areas(L1-NC)

Number of persons

% Number of persons

%

0-20 577 38.6 934 85.8

20-50 281 18.8 124 11.5

50-100 219 14.6 23 2.1

100-200 186 12.4 7 0.6

200-500 158 10.6 - -

500-1000 50 3.3 - -

>1000 25 1.7 - -

Total 1496 100 1088 100

1946-1958:

• 66 nuclear tests, ~100 MT

• Release of 131I:150 Chernobyl1500 Fukushima

• 1954: BRAVO test Resulted in high doses in northern atolls and to evacuations.

Nuclear weapons testing in the Marshall Islands

There are significant differences in estimating internal doses for Marshallese compared to estimating doses to populations exposed to fallout from the Chernobyl or Fukushima accidents:

1) No animal milk products available.

2) Unusual exposure pathways.

Bioassay of urine from Rongelap community members collected within 16 to19 days of fallout exposure from the BRAVO test provided the first ever measurements to confirm 131I from exposure to fallout.

Marshall Islands: person-based measurements

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Estimates of thyroid dose (mGy) to adults

Majuro Kwajalein Utrik Rongelap

Internal dose(short-term)

22 66 740 7,600

Internal dose (long-term)

0.76 1.3 25 14

INTERNAL DOSE (TOTAL)

23 67 760 7,600

EXTERNAL DOSE 9.8 22 140 1,600

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Concluding remarks

Concluding remarks (1 of 2)

• All dose reconstructions are different because:– Radioactive releases are different– Environmental conditions are different– Population habits are different, and– Countermeasures are different.

• However, there are principles of dose reconstruction that apply to all environmental studies.

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Concluding remarks (2 of 2)

• It is important to obtain realistic estimates of dose because:– they may be used in research projects such as

epidemiologic studies or risk assessment, – the affected populations have the right to know the

extent to which they were exposed to radiation.

• Multi-agency cooperation and multi-disciplinary expertise is needed to obtain dose estimates of a high degree of reliability.

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Thank you for your attention