Childhood Thyroid Cancer in Russia Following the Chernobyl accident

V.K. IvanovChairman, Russian Scientific Commission on Radiological Protection

Medical Radiological Research Center National Radiation and Epidemiological Registry

The International Workshop on Radiation and Thyroid Cancer Japanese Ministry of the Environment (MoE)

Fukushima Medical University (FMU)The OECD Nuclear Energy Agency (NEA)

Tokyo, Japan, 21-23 February 2014

Questions… Increased thyroid cancer incidence in residents exposed to radiation following the Chernobyl accident in their childhood

Increase in background(non-radiation)

thyroid cancer incidence

radiation-inducedthyroid cancer incidence +

EstimatingSCREENING EFFECT

EstimatingRADIATION RISK

Why… & How estimate…?

NRER IS A PART OF MEDICAL RADIOLOGICAL RESEARCH CENTER OF

THE RUSSIAN MINISTRY OF HEALTH

The National Registry is the WHO Collaborating Centre for Research and Training in Radiation Epidemiology

23 regional centers4 000 hospitals and clinics

798 000 registered persons400 000 Individual doses

18 000 000 diagnoses

NATIONAL RADIATION AND EPIDEMIOLOGICAL REGISTRY

STRUCTURE OF THE REGISTERED PERSONS

COHORT SELECTED FOR ANALYSIS OF RADIATION RISK OF THYROID CANCERSize of Cohort: 309,130 individuals with known thyroid dose (people living in contaminated areas 137Cs ≥ 5 Ci/km2) Bryansk, Kaluga, Orel and Tula regions

1980 1986 1991 2008

registrationof persons

Start of follow-up

End of follow-up18 years

Follow-up period:

Age at exposure (1986), y

Registered persons

Observed cases

N % N

0-17 97,191 31 % 247

18 + 211,939 69 % 746

Total 309,130 100 % 993

Cases: 993 Thyroid cancers (ICD-10: C73)

AVERAGE THYROID DOSES IN THE SETTLEMENTS OF BRYANSK, KALUGA, OREL AND TULA OBLASTS

Ivanov VK, Kashcheev VV et al. Radiat Prot Dosimetry; 2012 Sep;151(3):489-99.

The individualized thyroid doses for cohort members have been defined as equal to the average age-specific thyroid doses in their settlements at 1986, according to the Russian official catalogue of average doses of exposure of the thyroid gland.

METHODS:

Excess relative risk (ERR) model

– observed increase in thyroid cancer incidence rate

0 – baseline thyroid cancer incidence rate

ERR – excess relative risk per 1 Gy

d – average absorbed dose for the thyroid gland

,dERR 10

METHODS:

Baseline thyroid cancer incidence rate

0rus – thyroid cancer incidence rate in Russia

SIR – standardized incidence ratio (SCREENING EFFECT)

SIRrus 00

Expected

ObservedSIR

METHODS:

Assessment of screening and dose response

Thyroid dose, Gy

SCREENING EFFECT

ERR (dose response)

,dERRSIRrus 10

SIRrus 0

rus0

Follow-up: 1991 – 2008Age at the time of the Chernobyl accident (years)

0-17 y 18 y and older

Number of persons 97,191 211,939

Number of cases 247 746

Mean dose in healthy cohort members (mGy) 188 37

Mean dose in cases (mGy) 225 32

SIR, SCREENING EFFECT (95% CI), p-value 7.80 (5.95; 9.81), p<0.001 3.73 (3.42; 4.07), p<0.001

ERR per 1 Gy (95% CI), p-value 3.58 (1.61; 5.57), p<0.001 -0.49 (-2.33; 1.36), p>0.5

SIR AND ERR OF THYROID CANCER IN REGISTERED POPULATION OF BRYANSK, KALUGA, OREL AND TULA OBLASTS

Cohort: 309,130 individuals (993 cases of thyroid cancer)

Follow-up: 1991 – 2008Age at the time of the Chernobyl accident (years)

0-17 y (boys) 0-17 y (girls)

Number of persons 44,598 52,593

Number of cases 61 186

Mean dose in healthy cohort members (mGy) 178 196

Mean dose in cases (mGy) 250 218

SIR, SCREENING EFFECT (95% CI), p-value10.55 (4.59; 17.80), p<0.001

7.48 (5.58; 9.61), p<0.001

ERR per 1 Gy (95% CI), p-value 6.70 (1.88; 23.13), p<0.001 2.68 (0.66; 5.60), p<0.001

SIR AND ERR OF THYROID CANCER AMONG CHILDREN AND ADOLESCENTS (0-17 y in 1986)

Sub-Cohort: 97,191 individuals (247 cases of thyroid cancer)

RELATIVE RISK OF THYROID CANCER AMONG CHILDREN AND ADOLESCENTS (in 1986) BY DOSE GROUPS

Dose group (mGy)

Mean dose (Gy)

Number of cases Person-years RR

(95% CI) p-value

0-0.05 0.027 49 288,218 1 (Reference)

0.05-0.1 0.072 53 318,536 1.01 (0.68; 1.49) > 0.5

0.1-0.15 0.124 37 212,491 1.18 (0.77; 1.81) 0.46

0.15-0.2 0.173 18 131,218 0.91 (0.52; 1.53) > 0.5

0.2-0.25 0.222 18 97,500 1.64 (0.93; 2.76) 0.085

0.25-0.3 0.273 16 75,420 2.15 (1.18; 3.69) 0.013

0.3-0.35 0.324 17 44,432 3.12 (1.75; 5.30) < 0.001

0.35-0.5 0.418 20 94,791 2.31 (1.35; 3.83) 0.003

> 0.5 0.860 19 107,504 2.40 (1.36; 4.03) 0.002

)( 00 irus DRRSIR Model of Relative Risk:

RELATIVE RISK OF THYROID CANCER AMONG CHILDREN AND ADOLESCENTS (0-17 y in 1986) BY DOSE GROUPS

0

1

2

3

4

5

6

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

Thyroid dose, Gy

RR

Internal control: 0-50 mGy

* Dashed line is RR=1+ERR, where ERR (3.58, 95% CI:1.61-5.57)

EXPANDED STUDY OF SCREENING EFFECT AND RADIATION RISK OF THYROID CANCER

Cohort of children and adolescents: 97,191 persons (0-17 y in 1986)(people living in contaminated areas 137Cs ≥ 5 Ci/km2)

1980 1986 1991 2008

registrationof persons

Start of follow-up

End of follow-up21 years

Extended Follow-up period:

Cases: 247 Thyroid cancers (ICD-10: C73)

2011

+ 25 cases = 272

Tasks… • SCREENING EFFECT as the function of time• Dose-response in low-dose range (< 250 mGy)

INCIDENCE RATE OF THYROID CANCER IN MALE POPULATION OF THE RUSSIAN FEDERATION

INCIDENCE RATE OF THYROID CANCER IN FEMALE POPULATION OF RUSSIAN FEDERATION

sex-ratio incidence:

OBSERVED AND EXPECTED NUMBER OF THYROID CANCER CASES AMONG CHILDREN AND ADOLESCENTS (0-17 y. in 1986)

BY CALENDAR PERIODS

SIR OF THYROID CANCER AMONG CHILDREN AND ADOLESCENTS AS A FUNCTION OF CALENDAR PERIOD

IMPORTANT! SIR includes the radiation risk => SIR ≠ SCREENING

Expected

ObservedSIR

Follow-up: 1991 – 20110-17 y at the time of the Chernobyl accident

published in RPD new analysis

Number of persons 97,191 97,191

Number of cases 247 272

Mean dose in healthy cohort members (mGy) 188 188

Mean dose in cases (mGy) 225 214

SIR, SCREENING EFFECT (95% CI), p-value 7.80 (5.95; 9.81), p<0.001 6.65 (5.15; 8.24), p<0.001

ERR per 1 Gy (95% CI), p-value 3.58 (1.61; 5.57), p<0.001 3.81 (1.81; 6.86), p<0.001

NEW ANALYSIS OF SIR AND ERR OF THYROID CANCER AMONG CHILDREN AND ADOLESCENTS

Cohort of children and adolescents: 97,191 persons 272 cases of thyroid cancer

Follow-up: 1991 – 20110-17 y at the time of the

Chernobyl accident

SCREENING EFFECT by periods, 95% CI

1991 – 1995 15.2 (10.6; 20.9)

1996 – 2000 7.5 (5.5; 9.9)

2001 – 2005 6.7 (5.1; 8.6)

2006 – 2011 7.0 (5.5; 8.8)

ERR per 1 Gy (95% CI), p-value 3.34 (1.39; 6.82), p<0.001

NEW ANALYSIS OF SIR AND ERR OF THYROID CANCER AMONG CHILDREN AND ADOLESCENTS

Cohort of children and adolescents: 97,191 persons 272 cases of thyroid cancer

NEW ANALYSIS OF SIR AND ERR OF THYROID CANCER AMONG CHILDREN AND ADOLESCENTS

Cohort of children and adolescents: 97,191 persons 272 cases of thyroid cancer

(PURE EFFECT)

Dose range,mGy

Average thyroid dose,

mGyCases

ERR per 1 Gy,(95% CI)

p-value

0 – 100 53.2 113 -2.99 (-6.76; 4.65) > 0.5

0 – 125 63.0 132 -1.63 (-4.82; 4.44) > 0.5

0 – 150 71.4 160 3.57 (-0.90; 12.3) 0.143

0 – 200 84.8 180 1.81 (-1.24; 7.25) 0.3

0 – 250 98.2 199 2.40 (-0.36; 7.18) 0.1

0 – 300 110.4 218 4.05 (1.09; 9.16) 0.003

0 – 500 139.6 253 5.15 (2.39; 9.73) < 0.001

0 – 1000 172.3 269 4.31 (2.16; 7.75) < 0.001

> 0 189.4 272 3.81 (1.81; 6.86) < 0.001

THYROID CANCER RISK AMONG CHILDREN AND ADOLESCENTS (BOTH SEXES)

IN LOW-DOSE RANGE Cohort of children and adolescents: 97,191 persons

272 cases of thyroid cancer

FITTED ATTRIBUTABLE RISK OF THYROID CANCER (BOTH SEXES) AS A FUNCTION OF AGE AT EXPOSURE

Attributable risk = radiation-induced cases

radiation-induced cases + spontaneous casesх 100 %

CONCLUSION

Data on Chernobyl are useful for estimating long-term radiological effects following the accident at the Fukushima-1 NPP.

Statistically significant SCREENING EFFECT on thyroid cancer incidence was detected in people lived in radioactively contaminated territories following the Chernobyl accident.

The SCREENING EFFECT depends on calendar period of follow-up. The highest value of SIR (15.2 95% CI: 10.6; 20.9) was observed in the earliest follow-up period, from 1991 to 1995.

Statistically significant radiation risk of thyroid cancer is for children and adolescents (0-17 years at the time of exposure) only .

Statistically significant radiation risk of thyroid cancer is associated with thyroid doses > 250 mGy.