Childhood Thyroid Cancer in Belarus Following the Chernobyl

Childhood Thyroid Cancer in Belarus Following the Chernobyl Accident Yu. Demidchik, M. Fridman

Part 1 THYROID CANCER STATISTICS – Two etiological forms (radiogenic and sporadic) – High incidence in children within the first decade after Chernobyl • Since 2001, only sporadic cases were diagnosed – Prevalence of PTC • Follicular, medullary or anaplastic carcinomas are extremely rare – Recently, about 50% of patients present micro carcinomas at diagnosis

Crude incidence and mortality for thyroid cancer (: 100 000) (1965– 2013) 14 In total, 23795 patients were diagnosed from 1970 12 Mortality rates are available only since 1990 10 (1747 patients died within 1990 -2013) 8 6 4 0 1965 1966 1967 1968 1969 1970 1971 1972 1973 1974 1975 1976 1977 1978 1979 1980 1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2

0 1971 1972 1973 1974 1975 1976 1977 1978 1979 1980 1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 Crude incidence and mortality for thyroid cancer in males (: 100 000) (1970– 2013) 5 4 3. 5 3 2. 5 2 1. 5 1 0. 5

0 1971 1972 1973 1974 1975 1976 1977 1978 1979 1980 1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 Crude incidence and mortality for thyroid cancer in females (: 100 000) (1970– 2013) 25 Incidence increased by 8 times as compared with 1986 20 15 10 5

Crude incidence (: 100 000) for thyroid cancer in different regions (1970– 2013) 30 25 Brest Vitebsk Gomel Grodno Minsk Mogilev Minsk city 20 15 10 5 2012 2010 2008 2006 2004 2002 2000 1998 1996 1994 1992 1990 1988 1986 1984 1982 1980 1978 1976 1974 1972 1970 0

Crude incidence (: 100 000) for thyroid cancer depending on age group (1970– 2013) 30. 00 00 -14 15 -19 25. 00 20 -24 25 -29 20. 00 30 -34 35 -39 15. 00 40 -44 45 -49 10. 00 50 -54 55 -59 5. 00 60 -64 65 -69 2012 2010 2008 2006 2004 2002 2000 1998 1996 1994 1992 1990 1988 1986 1984 1982 1980 1978 1976 1974 1972 1970 0. 00 70 -74 75 -79 80+

Part 2 THYROID CANCER IN CHILDREN – 1418 cases of thyroid carcinomas (under 19 y. o. ) were diagnosed in the period from 1986 and 2010 (all histological forms). – Of them, 1169 are available for assessment. – The individuals born after April, 1987 were considered as non-radiogenic.

The beginning of significant increase of incidence in exposed to 131 I Aged under 18 Aged over 19

2. 00 0. 00 1971 1972 1973 1974 1975 1976 1977 1978 1979 1980 1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 Crude incidence (: 100 000) in young age (1970– 2013) 16. 00 14. 00 12. 00 10. 00 8. 00 00 -14 15 -19 6. 00 20 -24 4. 00 25 -29 ?

Childhood crude incidence (: 100 000) for thyroid cancer in different regions (1970 -2013) 14 12 10 Brest Vitebsk Gomel Grodno Minsk Mogilev Minsk city 8 6 4 2 2010 2008 2006 2004 2002 2000 1998 1996 1994 1992 1990 1988 1986 1984 1982 1980 1978 1976 1974 1972 1970 0

Adolescent crude incidence (: 100 000) for thyroid cancer in different regions (1970 -2013) 40 35 30 Brest Vitebsk Gomel Grodno Minsk Mogilev Minsk city 25 20 15 10 5 2012 2010 2008 2006 2004 2002 2000 1998 1996 1994 1992 1990 1988 1986 1984 1982 1980 1978 1976 1974 1972 1970 0

Post Chernobyl thyroid cancer cases in children depending on place of residence at the time of Chernobyl accident (1986 -2005)

Thyroid cancer in Belarus Results of Screening Study Area Age group Period IPHEKA (Scientific report, 1996) Gomel region Children and adolescents at the time of accident Sasakawa (Proceedings of the 5 th Chernobyl Sasakawa Medical Cooperation Symposium, 1996) Gomel region Up to 9 years at the time of accident Sasakawa (Proceedings of the 5 th Up to 9 years at Mogilev Chernobyl Sasakawa Medical the time of region Cooperation Symposium, 1996) accident Belarus screening program (Drozd V. M. , 2003) Belarus screening program (Krysenko N. A. , 2003) Up to 14 years at Belarus the time of accident Gomel region Up to 14 years at the time of accident 15– 18 years at the time of accident Cases Prevalence male female Total 1990– 1992 — — 15/6946 2. 16/1000 1991– 1996 12 25 37 12/9485 1. 27/1000 25/10175 2. 46/1000 37/19660 1. 88/1000 1991– 1996 1 1 2 1/11663 0. 09/1000 1/12118 0. 08/1000 2/23781 0. 08/1000 1990– 1991 — — 7/1100 6. 36/1000 — — 0/25446 0/1000 — — 2/12129 0. 17/1000 2002

CHILDREN (under 15) n NODULES OF THEM CANCER 1999 2000 2001 151015 150381 144765 542 495 393 0. 36% 0. 33% 0. 27% 10 9 3 1. 85% 1. 82% 0. 76%

ADOLESCENTS (15– 18 yo) n NODULES OF THEM CANCER 1999 2000 2001 44859 49064 57068 513 547 655 1. 14% 1. 11% 1. 15% 6 11 21 1. 17% 2. 01% 3. 21% 17

ADULTS (19+ yo) n NODULES OF THEM CANCER 1999 2000 2001 96928 100169 80541 7405 7635 7195 7. 64% 7. 62% 8. 93% 299 298 237 4. 01% 3. 92% 3. 29%

POST CHERNOBYL (RADIOGENIC) PATIENTS-1 Total number of cases: 936 (non-PTC cases and irradiated previously for other malignancies excluding) – Females: 600 (64. 1%) – Males: 336 (35. 9%) – Ratio: 1. 8: 1 Age: 4. 2 – 18. 99 (13. 6) – Under 10 y. o. : 157 (16. 8%) – 11 -14 y. o. : 364 (38. 9%) – 15 -18 y. o. : 415 (44. 3%)

POST CHERNOBYL (RADIOGENIC) PATIENTS-2 • Tumor size – Average: 14. 4 mm (range 1 -124 mm) • From 1 to 5 mm: 84 cases • From 6 to 10 mm: 302 • Above 11 mm: 550 (58. 8%) • Involved lymph nodes – N 0 : 246 (26. 3%) – N 1 a: 309 (33. 0%) – N 1 b: 381 (40. 7%) (73. 7%) (41. 2%)

POST CHERNOBYL (RADIOGENIC) PATIENTS-3 • Distant metastases at primary diagnostics — 104 (11. 1%). • Extrathyroidal extent – 387 (41. 3%). !Note! In 262 (28. 0%), the capsular involvement is not assessed. • Multifocality – 60 (6. 4%)

POST CHERNOBYL (RADIOGENIC) PATIENTS-4 • Pathological features – – – Classical PTC – 360 (38. 5%) Follicular variant – 292 (31. 2%) Diffuse sclerosing variant – 73 (7. 8%) Tall cell – 65 (6. 9%) Clear cell – 10 (1. 1%) Solid – 136 (14. 5%) • Involved blood vessels – 176 (18. 8%) • Involved lymphatic vessels – 790 (84. 4%)

POST CHERNOBYL (RADIOGENIC) PATIENTS-5 • Thyroid background – 148 (15. 8%), including – Autoimmune thyroiditis – 72 – Follicular adenoma – 20 – Nodular goiter – 56 • Dominant architectonics – Papillary – 300 (32. 1%) – Follicular – 453 (48. 4%) – Solid – 183 (19. 6%)

CONCLUSION#1 Post Chernobyl (radiogenic) PTC is frequently extrathyroidal. The tumor size in largest measurement is usually small but associated with high frequency of neck lymph nodes involvement (73. 7%) and distant metastases (11. 1%)

TOTAL THYROIDECTOMY + BILATERAL SELECTIVE NECK DISSECTION (LEVELS VI, II-IV) RADIOIODINE UPTAKE I-131 RADIOIODINE THERAPY L-T 4 SUPRESSIVE THERAPY

Multivariate analysis of local or regional recurrence Variables β p-value RR 95% CI Age at surgery 0. 5855 0. 1041 1. 80 0. 88 -3. 64 Multifocal carcinomas 1. 0762 0. 0049 2. 93 1. 39 -6. 21 N 1 b 0. 5920 0. 0361 1. 81 1. 04 -3. 14 Involved blood vessels 0. 4734 0. 0976 1. 61 0. 92 -2. 81 Involved lymphatic vessels 1. 2845 0. 0900 3. 61 0. 82 -15. 95 Thyroid background -1. 0669 0. 1461 0. 34 0. 08 -1. 45 Intrathyroidal dissemination 0. 6483 0. 0309 1. 91 1. 06 -3. 45 Thyroid lobectomy 1. 8122 <0. 0001 6. 12 3. 38 -11. 11

The risk of recurrence

CONCLUSION#2 • Local or regional recurrence after thyroidectomy is likely for 5 years and distant metastases can spread for 6 years. • In cases of surgery other than thyroidectomy, the probability of local or regional recurrence is high in any terms of follow-up. • Distant metastases can be detected within 10 years after partial thyroid resections.

Fine Grey regression model for distant metastases Variables β p-value RR 95% CI Childhood age at surgery 6. 13 0. 0150 6. 13 1. 43 – 26. 3 Involved blood vessels 2. 16 0. 0002 8. 68 2. 75 – 27. 4 No RIT 2. 23 0. 0003 9. 26 2. 74 – 31. 2

CONCLUSION#3 • To avoid local or regional recurrence in children and adolescents with PTC, primary surgery has to be based on total thyroidectomy followed by radioiodine therapy depending on indications • Despite this strategy, distant metastases can appear 5 -6 years after surgery being associated with tumor peculiarities: involved blood vessels, patients’ age and refusal from radioiodine

Part 3 SPORADIC THYROID CANCER IN CHILDREN

No clear evidence of geographical factor in sporadic cases (n=210; 1986– 2010)

Differences between sporadic and radiogenic cancer Sporadic carcinomas were significantly more common on abnormal thyroid background. In sporadic cases, lung metastases are significantly less common as compared with radiogenic carcinomas (2 cases; 1. 4%).

Crude incidence in different periods and age groups Age group Radiogenic Sporadic 1990– 1995 1996– 2001 2002– 2005– 2010 0– 18 2. 72 3. 22 1. 29 1. 16 0– 14 2. 88 2. 24 0 0. 62 15– 18 2. 09 6. 24 4. 48 2. 54

Observed survival (96. 9%)

Causes of death in 26 pts • • • Cause specific death: 2 Acute leukemia: 2 Gastric cancer: 1 (totally 10 pts have second cancer) Accidents and traumatic lesions: 6 Suicide: 7 Surgical complications: 1 Lung fibrosis: 1 Liver cirrhosis: 1 Cardiac failure: 1 +2 sporadic Mixedema: 1 Brain infarction: 1

CONCLUSION#4 The prognosis in childhood and adolescent thyroid cancer is favorable.

Acknowledgment • • • Dr. Yu. Averkin Prof. D. Williams Prof. K. W. Schmid Prof. C. Reiners Dr. M. Fridman O. Krasko

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