1Institute of Endocrinology and Metabolism, Kyiv, Ukraine2U.S. National Cancer Institute, Bethesda, U.S.A

3Scientific Centre for Radiation Medicine, Kyiv, Ukraine4 Ukrainian National Cancer Institute, Kyiv, Ukraine

Tronko M.1*, Bogdanova T.1 , Mabuchi K.2, Hatch M.2, Likhtarev I.3, Bouville A.2, Oliynik V.1, Shpak V.1, Tereshchenko V.1, Brenner A.2, Zurnadzgy L.1, Zamotaeva G.1, Gulak L.4, Shchepotin I.4

CHILDHOOD THYROID CANCER IN UKRAINE FOLLOWING

THE CHERNOBYL ACCIDENT

The International Workshop on Radiation and Thyroid Cancer,

21 – 23 February 2014 ,Tokyo, Japan

Comparison of radioactive iodine I131 fallout from nuclear reactors

Episode I131 fallout (Curie)Accident at Three Mile Island Nuclear Power Station, U.S.A (1979) Accident at the reactor “Windscale”, UK (1957) 20 000

Technological fallout from a reactor in the process of plutonium production at the enterprise in Hanford, Washington, U.S.A.

690 000

Accident at Chernobyl Nuclear Power Station, Ukraine (1986)* Accident at Fukushima Nuclear Power Station, Japan (2011)**

* In addition, fallouts of short-lived iodine and tellurium isotopes are estimated to be equal to 100,000,000 Curie (UNSCEAR 2008). ** Report of Japanese Government to IAEA Ministerial Conference on Nuclear Safety - Accident at TEPCO's Fukushima Nuclear Power Stations, 7 June 2011

15-20

40 000 000 – 50 000 000

4 000 000 – 5 000 000

Cumulative I-131 fallout on the soil (MBq/m2)

0.16 mean regional values of I131 fallout (kBq/m2)

Likhtarev et al., “Radiation and risk", 2005

Cumulative fallout of I131 in the territory of Ukraine as a result of the Chernobyl accident (April 26th – May 7th, 1986)

Main components of Clinical-Morphological Registry (CMR)

Personal records

Clinical data

Demography Pathology

Preliminary activity 1990– 1991Formally established by Ukraine Ministry of Public Health in order N12 January 20th, 1992 “On the improvement of endocrinological care to children and adolescent with thyroid diseases”

Cooperation between CMR and some other projects

Clinical-Morphological

Register, IEM, Kiev

National Cancer Registry of Ukraine,

National Cancer Institute, Ukraine, Kiev

TherDep, IEM, Kiev

Chernobyl Tissue Bank

Current number of thyroid cancer cases registered in CMR

(1986 – 2012)

Population groupsThyroid cancer cases

Male Female Both0-14 years old at the time of the accident 1221 5163 638415-18 years old at the time of the accident 342 1668 2010Exposed in utero 44 111 155Born in 1987 and later 181 652 833Total 1788 7594 9382

Time trends of thyroid cancer incidence in 6 and 21 regions of Ukraine among children aged 0-14 years

at the time of accident

Time trends of thyroid cancer incidence in 6 and 21 regions of Ukraine among adolescents aged 15-18

years at the time of accident

Time trends of thyroid cancer incidence in 6 and 21 regions of Ukraine among children

aged 0-14 years at surgery

Time trends of thyroid cancer incidence in 6 and 21 regions of Ukraine among adolescents

aged 15-18 years at surgery

Time trends of thyroid cancer incidence in 6 and 21 regions of Ukraine among adults

aged 19+ years at surgery

12 thyroid cancer cases revealed in 6 regions of Ukraine in 1986-1988

59 suspicious or thyroid cancer cases, detected on September 30, 2013 in results of examination

238 789 Japan children

(Proceedings of the 13th Prefectural Oversight Committee Meeting for Fukushima Health Management Survey. Thyroid Ultrasound

Examination. 12 November 2013)

Distributions of thyroid cancer cases by age at exposure in Ukraine and Fukushima

111 thyroid cancer cases revealed in 6 regions of Ukraine in 1990-1992

Histological types of thyroid carcinomas

TypeBorn before Chernobyl

number %PTC 2976 93.3FC 160 5.0MTC 48 1.5PDC 6 0.2Total 3190 100

PTC – papillary thyroid carcinoma; FC – follicular carcinoma; MTC – medullary carcinoma; PDC – poorly differentiated carcinoma

Ukrainian-American Thyroid Project

Stezhko et al., Rad. Res., 2004

UkrAm cohort thyroid study – a classical prospective cohort study of radiation risk of thyroid cancer and other thyroid pathology in Ukrainian exposed as children and adolescent due to Chernobyl accident and having direct thyroid activity measurements in May-June 1986.

Distribution of selected and examined cohort by dose group

Dose group A7542 (57.0%)

Dose group B3457 (26.1%)

Dose group C2244 (16.9%)

Number of cohort members examined

13243

Total number of records selected from dose file

34092

Dose group A D<0,3Gy

Low dose15541(45.6%)

Dose group B 0,3<D<1,0GyMiddle dose 8476(24.9%)

Dose group C D>1,0Gy

High dose 10075 (29.6%)

Residence of cohort members in 1986

Geographic distribution of cohort members that underwent examination in 1998-2000

Number of cohort members that underwent different screening rounds

0

2,000

4,000

6,000

8,000

10,000

12,000

14,000 13,243 12 419(93.8%) 11 744

(88.7%)10 186(76,9%)

Series1

Standardized clinical examination procedure

Thyroid palpation

Ultrasound examination

Individual medical history documentation

Blood sample to determine thyroid hormone levels

Urinary iodine content test

Extended structured dosimetry interviews

FNA test and surgery (if recommended)

Endocrinology conclusion and recommendations

Nodular pathology examination

Ultrasound examination

No thyroid nodular abnormality

Thyroid benign pathology

Thyroid carcinoma

Thyroid nodule or lesion, FNA not

recommended

FNA test I. Non informative FNA

II. Benign nodular goiter

Thyroid surgery, Pathology diagnosis, IPP (CTB) verification

III. Follicular neoplasia

IV. Suspected carcinoma V. Carcinoma

Thyroid nodule

or lesion

Next exam two years after

Next exam six months after

Thyroid cancer cases revealed during the 1st, 2nd, 3rd and 4th cycles of screening (110 cases)

29 (17+5+1+6)

60 (18+21+11+10)

21 (10+6+5+0)

Number of thyroid cancer cases per 1,000 study subjects detected during 1st - 4th screening cycles

Dose A: 7542 (<0,3Gy)

Dose B: 3457 (0,3-0,99Gy)

Dose C: 2244 (>=1Gy)

05

10152025

1.3 3.5

10.210 12

231st screening

Dose A: 7113

Dose B: 3223

Dose C: 2083

05

10152025

1.7 3.4 4.3

12 11 9

2nd screening

Dose A: 6714

Dose B: 3053

Dose C: 1978

05

10152025

1.2 2 1.5

8 63

3rd screening

Dose A: 5868

Dose B: 2652

Dose C: 1666

05

10152025

1.5 1.9 1.2

95

2

4th screening

Number per 1000 subjects in each dose group Number of cases

Histological types of thyroid carcinomas (110 cases)

1st 2nd 3rd 4th0

5

10

15

20

25

30

35

40

45 43

30

16 15

2 1 1 10 1 0 0

Papillary carcinomaFollicular carcinomaMedullary carcinoma

screenings

case

s

Prospects for scientific investigations

• Assessment of the risk for thyroid cancer as a result of the Chernobyl accident

UkrAm: estimates of thyroid cancer risk

• In the cohort 13127 screened subjects during 1998-2000 45 thyroid cancer cases were detected.

• The excess relative risk per gray (Gy) was estimated using individual doses and a linear excess relative risk model.

• Thyroid cancer showed a strong, monotonic, and approximately linear relationship with individual thyroid dose estimate ( P <.001), yielding an estimated excess relative risk of 5.25 per Gy (95%CI = 1.70 to 27.5). In the absence of Chernobyl radiation, 11.2 thyroid cancer cases would have been expected compared with the 45 observed.

Prevalence: cases diagnosed in 1998-2000

Tronko M.D., Howe G.R., Bogdanova T.I. et al. JNCI, Vol. 98, 2006Dose-response prevalence of thyroid cancers detected during first screening cycle (1998-2000)

UkrAm: estimates of thyroid cancer risk

Brenner A.V., Tronko M.D., Hatch М., Bogdanova T.I. et al. EHP, March 2011, doi: 10.1289/ehp.1002674I-131 Dose-Response for Incident Thyroid Cancers in Ukraine Related to the Chernobyl Accident

Incidence: cases diagnosed in 2001-2008

• There were 65 incident thyroid cancers diagnosed during the 2nd-4th screenings in 2001-2008 (N=12514 ) and about 73,000 person-years of observation.

• The ERR per Gy was estimated 1.91 (95% CI: 0.43-6.34) and EAR per 104 PY per Gy was 2.21 (95% CI: 0.04 - 5.78).

The ERR per Gy varied significantly by oblast of residence, but not by time since exposure. I-131-related thyroid cancer risks persisted for two decades following exposure.

CONCLUSIONS I

Among the exposed population of children and adolescents (aged 0-18 years at the time of accident) observed a significant increase in thyroid cancer incidence beginning from 1990. This tendency persists for the period of 22 years (1990-2012).

Incidence rate in the 6 most contaminated regions exceeded that in 21 low-contaminated regions for all periods of study.

By age at surgery, peak incidences in childhood and adolescent groups were observed in 1996-1998 and 2000-2002, respectively.

Age distribution of subjects with radiogenic thyroid cancer in Ukraine for shortest latency of tumor development (4-6 years) is characterized by realization of radiation effect in youngest groups at the time of the accident and significantly differs from that observed in Fukushima after screening examinations.

CONCLUSIONS II

The number of thyroid cancer cases per 1,000 study subjects of UkrAm thyroid cohort study was decreasing with each subsequent screening but after the fourth two-year cycle it also remained at a significant level: 1.5 cases per 1000 study subjects.

During the first and second cycles the number of thyroid cancer cases per 1,000 study subjects was increasing with increasing of thyroid exposure doses. During third and fourth cycles of screening such relationship has not been established.

As a result of four cycles of screening examinations, 110 cohort members with thyroid cancer have been operated on during 1998-2008.

Among 110 thyroid carcinomas revealed during four screenings papillary carcinoma was predominant: 104 cases (94.5%).