Kronach, 3.5.2011
description
Transcript of Kronach, 3.5.2011
Kronach, 3.5.2011
CRPPH Workshop Tokyo 21-23. 2. 2014-
Radiation and Thyroid Cancer
Chr.Reiners, Wuerzburg
Chr.Reiners, Universitätsklinikum WürzburgNational WHO-Collaboration Center - Radiation Emergency Preparedness Assistance NetworkHead: Prof.Dr.Chr.ReinersAffiliated toDepartment of Nuclear MedicineUniversity of Wuerzburg, GermanyDirector: Prof.Dr.A.Buck
Radiation Induced Thyroid Cancer
ISI Web of Science 15.02.14: 1702 Publications since 1950
1970 1980 1990 2000 2010
Radiation Induced Thyroid Cancer
Outline:
1. Thyroid Cancer Epidemiology Worldwide2. Radiation Exposure: Experiences of the Past3. The Chernobyl Reactor Accident4. Genetic Susceptibility
5. Clinical Presentation and Diagnosis6. Treatment and Prognosis
Thyroid Cancer Epidemiology Worldwide
IARC Cancer in Five Continents 2010
Age standardized incidence ratios 1980 - 2002
Females MalesScale factor x 2,5
Radiation Induced Thyroid Cancer
Increasing Incidence – Questions:
• True increase of thyroid cancer incidence?
• Age dependancy of assumed increase?
• Radiation as possible carcinogen?
• Genetic fingerprint of radiation carcinogenesis?
US SEER Cancer Registry 2005: Thyroid
6
Chen et al. Cancer 2009
Incidence
Females
Males
< 1,0 cm 1,0-2,9 cm 3,0-3,9 cm > 4,0 cm
appr. 50% of the effect in tumors < 1,0cm
Epidemic of Thyroid Cancer in the US 2005-2009:Role of Endocrinologists and Ultrasound
Udelsman & Zhang Thyroid 2013
Age Stand.Incidence Rate by State
Density of Endocrinologistsr=0.44, P=0.0031
Counts of Neck Ultrasonographyr=0.40, P=0.0091
Explaining 57% of the Variability in
State-Level Cancer Incidence
Radiation Induced Thyroid Cancer
Increasing Incidence - Questions
• True increase of thyroid cancer incidence?
• Age dependancy of assumed increase?
• Radiation as possible carcinogen?
• Genetic fingerprint of radiation carcinogenesis?
Childhood Thyroid Cancer: US SEER 2008
Hogan et al J Surg Res 2009
Radiation Induced Thyroid Cancer
Increasing Incidence – Questions
• True increase of thyroid cancer incidence?
• Age dependancy of assumed increase?
• Radiation as possible carcinogen?
• Genetic fingerprint of radiation carcinogenesis?
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
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
The New York Times 30.01.2014
Radiation Induced Thyroid Cancer: The Role of X –Ray and CT?
Daily Release of I-131, Te-132 and Cs-137 during 10 Days
after April 26 1986 at the Cernobyl NPP
Graphite-Fire
Activity Concentration of Cs-137 in Cows MilkActivity Concentration of Cs-137 in Cows MilkRovno, Ukraine 1988-2000Rovno, Ukraine 1988-2000
Permitted Level
Average Thyroid Doses per District after ChernobylAverage Thyroid Doses per District after Chernobyl
Demidchick 2003
0-4 Years
4-14 Years
> 14 Years
Thyroid Cancer Incidence in Children and AdolescentsThyroid Cancer Incidence in Children and Adolescents from Belarus after the Chernobyl Accidentfrom Belarus after the Chernobyl Accident
Basal Incidence0,5/100.000 (USA)
Additional Relative Risk for Thyroid Cancer in Different Additional Relative Risk for Thyroid Cancer in Different Age Groups after the Chernobyl Accident (Exposure 1Gy)Age Groups after the Chernobyl Accident (Exposure 1Gy)
P.Jacob et al Rad Res 2006
Age at the time of surgery
Age at the time of exposureA
dddi
tiona
l rel
ativ
e ris
k
Increased Risk after > 0,1 Gy only in Children 0-17 years of age
Ivanov V.K. et al, Radiation Protection Dosimetry 2012
Post Chernobyl Cases and Baseline Incidence in Children Post Chernobyl Cases and Baseline Incidence in Children and Adolescents after the Chernobyl Accidentand Adolescents after the Chernobyl Accident
Jacob, Goulko et al Rad Res 2006
Belarus: Thyroid Cancer in Children and Adolescents
Tyro
id C
ance
rs C
ases
per
Yea
r
Observed cases
Spontaneous cases
Radiation Induced Thyroid Cancer
Increasing Incidence – Questions:
• True increase of thyroid cancer incidence?
• Age dependancy of assumed increase?
• Radiation as possible carcinogen?
• Genetic fingerprint of radiation carcinogenesis?
Nikiforov Y.E., Nikiforova M.N., Nat Rev Endocrinol 2011
Molecular Genetics of Thyroid Cancer
Nikiforov Y.E., Nikiforova M.N., Nat Rev Endocrinol 2011Leerman –Neill R.J. et al Cancer 2013
Molecular Genetics of Thyroid Cancer
FOXE1: Metaanalysis of Common Genetic Variants (SNP´s) and Differentiated Thyroid Cancer Risk
Hongling Zhu et al PLoS One 2013
Overall
FOXE1 is a Major Genetic Determinant for Radi-ation Related Thyroid Cancer after Chernobyl
Takahashi M et al Human Mol Genetics 2010
Radiation Induced Thyroid Cancer
Outline:
1. Thyroid Cancer Epidemiology Worldwide2. Radiation Exposure: Experiences of the Past3. The Chernobyl Reactor Accident4. Genetic Susceptibility
5. Clinical Presentation and Diagnosis6. Treatment and Prognosis
Diagnosis of Thyroid Cancer in Children by Diagnosis of Thyroid Cancer in Children by Gray Scale and Power-Doppler UltrasoundGray Scale and Power-Doppler Ultrasound
Lyshchik A, Drozd V, Demidchik Y, Reiners C Radiology 2005
Multivariate Logistic Regression
t-Value P
Nodule size
Hypoechogenicity
Outline irregularity
Subcapsular location
Increased peri-/intranodular
vascularisation
3.63
2.55
3.93
3.87
3.34
< 0.001
< 0.05
< 0.001
< 0.001
< 0.01
35 malignant, 68 benign nodules; mean age 14.2 + 2.7 years
Presentation, Treatment and Outcome of DTC in Children and Adolescents: Summary of the Literature 1987-2012
Reiners C. et al J Clin Endocrinol 2013
Presentation of DTC in Children and Adolescents: Summary of the Literature 1987-2012
Reiners C. et al J Clin Endocrinol 2013
Treatment of DTC in Children and Adolescents: Summary of the Literature 1987-2012
Reiners C. et al J Clin Endocrinol 2013
Histology 232 Papillary Cancers (99.1%) 2 Follicular Cancers ( 0.9%)
Stage
advanced
pT1 5 pT2 75 pN0 7 pM0 134 pT3 4
pT4 150 pN1 227 pM1 100 (64%) (97 %) (42%)
Reiners C. et al J Clin Endocrinol 2013
Children with Thyroid Cancer from Belarus (I-131-Treatment in Germany 04/1993 to 04/2012)
1.Therapy 2/95 Activ. 6 GBq I-131Tg: 438 ng/ml
3.Therapy 12/95Cum. Activ. 18 GBq I-131Tg: 73 ng/ml
4.Therapy 7/96Cum. Activ. 24. 2 GBq I-131Tg: 2 ng/ml
G. A. * 05.02.1982, papillary DTC., pT4 N1b M1
Results of I-131 Therapy in 229 Childrenwith Thyroid Cancer from Belarus 1993-2012
(134 M0 / 100 M1)
Reiners C. et al J Clin Endocrinol 2013
1 cancer related case of death,2 cases of recurrencies
Outcome of DTC in Children and Adolescents: Summary of the Literature 1987-2012
Reiners C. et al J Clin Endocrinol 2013
Acknowledgements
Prof.E.P.Demidchik †, Prof.Y.E.Demidchik,
Prof.V.M.Drozd, MinskSupported in part by the Federal Ministry of Radiation Protection
Dr.A.Lyshik, Minsk – Kyoto – Nashville
Prof.S.Yamashita, Nagasaki - Fukushima
Prof.V.A.Saenko, NagasakiSupported in part by the Nagasaki University 21st Century COE Program
Dr.J.Biko, Wuerzburg