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Kronach, 3.5.2011

CRPPH Workshop Tokyo 21-23. 2. 2014 - Radiation and Thyroid Cancer Chr.Reiners , Wuerzburg. Kronach, 3.5.2011. Chr.Reiners, Universitätsklinikum Würzburg. National WHO-Collaboration Center - Radiation Emergency Preparedness Assistance Network Head: Prof.Dr.Chr.Reiners Affiliated to

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Kronach, 3.5.2011

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  1. CRPPH Workshop Tokyo 21-23. 2. 2014 - Radiation andThyroidCancer Chr.Reiners, Wuerzburg Kronach, 3.5.2011 Chr.Reiners, Universitätsklinikum Würzburg National WHO-Collaboration Center - Radiation Emergency Preparedness Assistance Network Head: Prof.Dr.Chr.Reiners Affiliated to Department of Nuclear Medicine University of Wuerzburg, Germany Director: Prof.Dr.A.Buck

  2. RadiationInducedThyroidCancer 1970 1980 1990 2000 2010 ISI Web of Science 15.02.14: 1702 Publications since 1950

  3. Radiation Induced Thyroid Cancer Outline: Thyroid Cancer Epidemiology Worldwide Radiation Exposure: Experiences of the Past The Chernobyl Reactor Accident Genetic Susceptibility Clinical Presentation and Diagnosis Treatment and Prognosis

  4. Thyroid Cancer Epidemiology Worldwide Females Males Scale factor x 2,5 Age standardized incidence ratios 1980 - 2002 IARC Cancer in Five Continents 2010

  5. RadiationInducedThyroidCancer • Increasing Incidence – Questions: • True increase of thyroid cancer incidence? • Age dependancy of assumed increase? • Radiation as possible carcinogen? • Genetic fingerprint of radiation carcinogenesis?

  6. US SEER Cancer Registry 2005: Thyroid Incidence 1,0-2,9 cm < 1,0 cm > 4,0 cm 3,0-3,9 cm Females appr. 50% of the effect in tumors < 1,0cm Males Chen et al. Cancer 2009

  7. EpidemicofThyroidCancer in the US 2005-2009: RoleofEndocrinologistsand Ultrasound Age Stand.Incidence Rate by State Density of Endocrinologists r=0.44, P=0.0031 Counts of Neck Ultrasonography r=0.40, P=0.0091 Explaining 57% of the Variability in State-Level Cancer Incidence Udelsman & Zhang Thyroid 2013

  8. RadiationInducedThyroidCancer • Increasing Incidence - Questions • True increase of thyroid cancer incidence? • Age dependancy of assumed increase? • Radiation as possible carcinogen? • Genetic fingerprint of radiation carcinogenesis?

  9. Childhood Thyroid Cancer: US SEER 2008 Hogan et al J Surg Res 2009

  10. RadiationInducedThyroidCancer • Increasing Incidence – Questions • True increase of thyroid cancer incidence? • Age dependancy of assumed increase? • Radiation as possible carcinogen? • Genetic fingerprint of radiation carcinogenesis?

  11. THYROID CANCER AFTER EXPOSURE TO IRRADIATION Cohort and Screening Studies of Children Study observ./expect. mean average excess cases dose relat.risk at 1Sv Life Span Study (0-19y) 59 22.2 0.26 Sv 6.3(95%CI: 5.1-10.1) Israeli Tinea Capitis 43 10.7 0.1 Sv 34(95%CI: 23-47) Rochester Thymus 37 2.7 1.4 Sv 9.5(95%CI: 6.9-12.7) Lymphoid Hyperplasia 13 5.4 0.24 Sv 5.9(95%CI: 1.8-11.8) Michael Reese Tonsils 309 110.4 0.6 Sv 3.0(95%CI: 2.6-3.5) All 436 -- -- 4.4 (95%CI: 1.9-10.1) E.Ron, Radiat.Res. 1995 significant

  12. THYROID CANCER AFTER EXPOSURE TO IRRADIATION The Life Span Study from Japanese A-Bomb Survivors Study observ./expect. mean average excess cases dose relat.risk at 1Sv All 132 94.3 0.26 Sv 1.5 (95%CI:0.5-2.1) Sex male 22 14.9 0.27 Sv 1.80 female 110 79.4 0.26 Sv 1.49 Age at exposure 0-9 years 24 7.6 0.21 Sv 10.25 10-19 35 14.6 0.31 Sv 4.50 20-29 18 17.5 0.28 Sv 0.10 Thompson, Radiat.Res. 1994 significant

  13. Radiation Induced Thyroid Cancer: The Role of X –Ray and CT? The New York Times 30.01.2014

  14. Daily Release of I-131, Te-132 and Cs-137 during 10 Days after April 26 1986 at the Cernobyl NPP Graphite-Fire

  15. Activity Concentration of Cs-137 in Cows Milk Rovno, Ukraine 1988-2000 Permitted Level

  16. Average Thyroid Doses per District after Chernobyl

  17. Thyroid Cancer Incidence in Children and Adolescents from Belarus after the Chernobyl Accident 4-14 Years > 14 Years 0-4 Years Basal Incidence 0,5/100.000 (USA) Demidchick 2003

  18. Additional Relative Risk for Thyroid Cancer in Different Age Groups after the Chernobyl Accident (Exposure 1Gy) Age at the time of exposure Addditional relative risk Age at the time of surgery P.Jacob et al Rad Res 2006

  19. IncreasedRisk after > 0,1 Gy only in Children 0-17 yearsofage Ivanov V.K. et al, Radiation Protection Dosimetry 2012

  20. Post Chernobyl Cases and Baseline Incidence in Children and Adolescents after the Chernobyl Accident Belarus: Thyroid Cancer in Children and Adolescents Observed cases Tyroid Cancers Cases per Year Spontaneous cases Jacob, Goulko et al Rad Res 2006

  21. RadiationInducedThyroidCancer • Increasing Incidence – Questions: • True increase of thyroid cancer incidence? • Age dependancy of assumed increase? • Radiation as possible carcinogen? • Genetic fingerprint of radiation carcinogenesis?

  22. MolecularGeneticsofThyroidCancer Nikiforov Y.E., Nikiforova M.N., Nat Rev Endocrinol 2011

  23. MolecularGeneticsofThyroidCancer Nikiforov Y.E., Nikiforova M.N., Nat Rev Endocrinol 2011 Leerman –Neill R.J. et al Cancer 2013

  24. FOXE1: Metaanalysis of Common Genetic Variants (SNP´s) and Differentiated Thyroid Cancer Risk Overall Hongling Zhu et al PLoS One 2013

  25. FOXE1 is a Major Genetic Determinant for Radi- ation Related Thyroid Cancer after Chernobyl Takahashi M et al Human Mol Genetics 2010

  26. Radiation Induced Thyroid Cancer Outline: ThyroidCancerEpidemiology Worldwide Radiation Exposure: ExperiencesofthePast The ChernobylReactorAccident GeneticSusceptibility Clinical Presentationand Diagnosis Treatment and Prognosis

  27. Diagnosis of Thyroid Cancer in Children by Gray Scale and Power-Doppler Ultrasound 35 malignant, 68 benign nodules; mean age 14.2 + 2.7 years Lyshchik A, Drozd V, Demidchik Y, Reiners C Radiology 2005

  28. Presentation, Treatment and Outcome of DTC in Children and Adolescents: Summary of the Literature 1987-2012 Reiners C. et al J Clin Endocrinol 2013

  29. Presentation of DTC in Children and Adolescents: Summary of the Literature 1987-2012 Reiners C. et al J Clin Endocrinol 2013

  30. Treatment of DTC in Children and Adolescents: Summary of the Literature 1987-2012 Reiners C. et al J Clin Endocrinol 2013

  31. Children with Thyroid Cancer from Belarus (I-131-Treatment in Germany 04/1993 to 04/2012) Reiners C. et al J Clin Endocrinol 2013

  32. 1.Therapy 2/95 Activ. 6 GBq I-131 Tg: 438 ng/ml 4.Therapy 7/96 Cum. Activ. 24. 2 GBq I-131 Tg: 2 ng/ml 3.Therapy 12/95 Cum. Activ. 18 GBq I-131 Tg: 73 ng/ml G. A. * 05.02.1982, papillary DTC., pT4 N1b M1

  33. Results of I-131 Therapy in 229 Children with Thyroid Cancer from Belarus 1993-2012 (134 M0 / 100 M1) 1 cancer related case of death, 2 cases of recurrencies Reiners C. et al J Clin Endocrinol 2013

  34. Outcome of DTC in Children and Adolescents: Summary of the Literature 1987-2012 Reiners C. et al J Clin Endocrinol 2013

  35. Acknowledgements Prof.E.P.Demidchik †, Prof.Y.E.Demidchik, Prof.V.M.Drozd, Minsk Supported in part by the Federal Ministry of Radiation Protection Dr.A.Lyshik, Minsk – Kyoto – Nashville Prof.S.Yamashita, Nagasaki - Fukushima Prof.V.A.Saenko, Nagasaki Supported in part by the Nagasaki University 21st Century COE Program Dr.J.Biko, Wuerzburg

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