1 Institute of Endocrinology and Metabolism, Kyiv, Ukraine 2 U.S. National Cancer Institute, Bethesda, U.S.A 3 Scientific Centre for Radiation Medicine, Kyiv, Ukraine 4 Ukrainian National Cancer Institute, Kyiv, Ukraine 1 Institute of Endocrinology and Metabolism, Kyiv, Ukraine 2 U.S. National Cancer Institute, Bethesda, U.S.A 3 Scientific Centre for Radiation Medicine, Kyiv, Ukraine 4 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 I 131 fallout from nuclear reactors * 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 – –

Cumulative I-131 fallout on the soil (MBq/m 2 ) 0.16 mean regional values of I 131 fallout (kBq/m 2 ) Likhtarev et al., “Radiation and risk", 2005 Cumulative fallout of I 131 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 dataDemography PathologyDosimetry Preliminary activity 1990– 1991 Formally 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 groups Thyroid cancer cases MaleFemaleBoth 0-14 years old at the time of the accident years old at the time of the accident Exposed in utero Born in 1987 and later Total

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

Histological types of thyroid carcinomas Type Born before Chernobyl number% PTC FC MTC481.5 PDC60.2 Total 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 A 7542 (57.0%) Dose group A 7542 (57.0%) Dose group B 3457 (26.1%) Dose group B 3457 (26.1%) Dose group C 2244 (16.9%) Dose group C 2244 (16.9%) Number of cohort members examined Number of cohort members examined Total number of records selected from dose file Total number of records selected from dose file Dose group A D<0,3Gy Low dose 15541(45.6%) Dose group A D<0,3Gy Low dose 15541(45.6%) Dose group B 0,3<D<1,0Gy Middle dose 8476(24.9%) Dose group B 0,3<D<1,0Gy Middle dose 8476(24.9%) Dose group C D>1,0Gy High dose (29.6%) Dose group C D>1,0Gy High dose (29.6%)

Residence of cohort members in 1986

Geographic distribution of cohort members that underwent examination in

Number of cohort members that underwent different screening rounds Number of cohort members that underwent different screening rounds

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 Thyroid nodule or lesion, FNA not recommended FNA test I. Non informative FNA II. Benign nodular goiter Thyroid surgery, Pathology diagnosis, IPP (CTB) verification Thyroid surgery, Pathology diagnosis, IPP (CTB) verification III. Follicular neoplasia IV. Suspected carcinoma V. Carcinoma Thyroid nodule or lesion 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 ( ) 60 ( ) 21 ( )

Number of thyroid cancer cases per 1,000 study subjects detected during 1 st - 4 th screening cycles Number of thyroid cancer cases per 1,000 study subjects detected during 1 st - 4 th screening cycles Number per 1000 subjects in each dose group Number of cases

Histological types of thyroid carcinomas (110 cases)

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

UkrAm: estimates of thyroid cancer risk Brenner A.V., Tronko M.D., Hatch М., Bogdanova T.I. et al. EHP, March 2011, doi: /ehp I-131 Dose-Response for Incident Thyroid Cancers in Ukraine Related to the Chernobyl Accident Brenner A.V., Tronko M.D., Hatch М., Bogdanova T.I. et al. EHP, March 2011, doi: /ehp I-131 Dose-Response for Incident Thyroid Cancers in Ukraine Related to the Chernobyl Accident Incidence: cases diagnosed in There were 65 incident thyroid cancers diagnosed during the 2nd-4th screenings in (N=12514 ) and about 73,000 person-years of observation. The ERR per Gy was estimated 1.91 (95% CI: ) and EAR per 10 4 PY per Gy was 2.21 (95% CI: ). 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 This tendency persists for the period of 22 years ( ). 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 and , 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 Among 110 thyroid carcinomas revealed during four screenings papillary carcinoma was predominant: 104 cases (94.5%).