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THYROID CANCER EVOLUTION OF THE DISEASE EVALUATED IN ONE SETTING

Histological profile of thyroid cancer between 1975-2009.Chernobyl effect and universal iodine fortification of salt. THYROID CANCER EVOLUTION OF THE DISEASE EVALUATED IN ONE SETTING. VOICHI ŢA MOGOŞ 1 . EUGEN TIRCOVEANU 2

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THYROID CANCER EVOLUTION OF THE DISEASE EVALUATED IN ONE SETTING

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  1. Histological profile of thyroid cancer between 1975-2009.Chernobyl effect and universal iodine fortification of salt THYROID CANCEREVOLUTION OF THE DISEASE EVALUATED IN ONE SETTING VOICHIŢA MOGOŞ1. EUGEN TIRCOVEANU2 1. Clinic of Endocrinology, 1st Surgery Clinici University of Medicine and Pharmacy “Gr.T Popa” Iasi

  2. PURPOSE To evaluate the evolution in time of incidence, clinical and histological profile in our setting from 1975 to 2009 taking into account two main events: • The accident from Chernobyl • The role of iodine prophylaxis

  3. Data from literature • There was noticed a steady increase of thyroid cancer all over the world • External irradiation in the only well documented cause in papillary thyroid cancer leading to RET/PTC re-arrangements • Iodine deficiency may play a role in the development of follicular cancer and may favor the development of anaplastic carcinoma • Iodine repletion is associated with increased incidence of papillary carcinoma with excellent prognosis

  4. There was noticed a steady increase of thyroid cancer all over the world Davies L et al. JAMA 2006, 295, 2164-2167 Between 1973-2002: • 2.4 times increase in thyroid cancer incidence • All thyroid cancer: 3.6/105 to 8.7/105/year (with 5.1/105) • Papillary cancer: 2.7/105 to 7.7/105/year • Small papillary cancer account for 87 % of the cancer • Mortality decreased from 0.57 to 0.47/105/year • External irradiation stopped after 1961 • Most data show that precocious diagnosis by ultrasound and FNB leads to increased incidence but stable mortality • Papillary cancer has a long evolution and excellent survival • Over diagnosis increased the number of radical surgery and its complications

  5. Davies L., Welch HG.JAMA 2006,295, 2164-2167

  6. Davies L., Welch HG.JAMA 2006,295, 2164-2167

  7. There was noticed a steady increase of thyroid cancer all over the world Schottenfeld D et al. CA Cancer J.Clin. 1978, 28, 66-86 USA:Connecticut Tumor registry • 1949-1969: 1.4/105/year to 1970-1983: 4/105/year • Papillary: 64 % • Follicular: 18 % • Medullary: 3 % • New York a study on autopsies: • 16.4 /1000 all study • 19.6/1000 in women • 10.4/1000 in men • Microcarcinomas: • USA: 1- 5.7 % • Japan: 17.9-24%

  8. There was noticed a steady increase of thyroid cancer all over the world Scheiden P.et al. BMC Cancer 2006, 6, 102-109 Evaluation in an European country – Luxembourg 30 years after Chernobyl in 2 cohorts: 1990-1994 (a) and 1995-1999 (b) • 310 new cases out of which 124 microcarcinomas < 1cm. After 1997 • Increased microcarcinomas from 7 % to 16.6 % • 46.5 % papillary • 13.3 % follicular • 27.3 % medullary • Increased incidence from 6.4 to 8.6/105/year • Increased incidence in women from 7.4 to 10.1/105/year • Increased incidence in men from 2.3 to 3.6 /105/year Mahoney MC et al. Int.Epidemiol. 2005, 34, 714-722 (1970-2001) • Severe exposure: increase incidence in males + 775%, in females:+1925% • Low exposure: increased incidence in males:+54 %, in females: + 250 %

  9. Luxembourg Scheider R et al. BMC Cancer 2006, 6, 102-116

  10. There was noticed a steady increase of thyroid cancer all over the world Leehardt L et al.Thyroid 2004, 14, 1056-1060 • FRANCE: 1998-2001 • Increased incidence of thyroid cancer • Increased prevalence of cancer operated among thyroid nodules submitted to surgery due to • increased assessment with ultrasound from 3 to 84 5 • Increased assessment through FNB from 8 to 36 % • In France there was notice no association between cancer incidence and nuclear accident from Chernobyl

  11. There was noticed a steady increase of thyroid cancer all over the world Reynolds RM et al. Clin.Endocrinol. (Oxf) 2005, 62, 156-162 Scotish Cancer Registry 1960-2000: • Incresed incidence of thyroid cancer from 1.76 to 3.54/105/year in women • Increased incidence from 0.82 to 1.25/105/year in men • Decreased mortality from 1.05 to 0.28 % in women and from 0.73 to 0.34 in men • Decreased follicular cancer • Stable incidence of medullary carcinoma • Increased survival

  12. External irradiation was the only well documented cause in papillary thyroid cancer leading to RET/PTC re-arrangements Data from internal irradiation are related to the best studied nuclear plant accident from Chernobyl

  13. Thyroid irradiation The role of external irradiation in induction of thyroid cancer was first noticed by Duffy and Fitzgerald in 1953, in those who received external irradiation for different diseases. 36 % of children who developed thyroid cancer had neck irradiation in their personal history The role of radioiodine was largely studied after Chernobyl Contamination: • Internal irradiation by inhalation or ingestion of: radioactive iodine 131I, 132I, 135I, 131mTe (tellurium). 133 Te • External irradiation X ray, gamma Irradiation due to radioactive material deposits on the ground1 • Belarus: cancer in children: 1/106 before and 100/106 after Chernobyl2. The risk in children less than 1 year is 30 fold greater3 Cardis E et al. J.Natl.Cancer Inst. 2005, 97, 724-732 Nagatachi S et al. Thyroid 2002, 12, 899-896 Boltze C et al. Oncology 2009, 22, 459-467

  14. Thyroid irradiation Questions: • Which is the role of the previous iodine intake in the contaminated area • Which are the factors that modify the risk of thyroid cancer after exposure to irradiation: • contamination level • individual factors Total dose of exposure: • 365 mGy in Belarus (7- 3109 mGy) • 40 mGy Rusian Federation (max. 10.2Gy) • Dose of exposure to radioiodine: 1-2 mGy Cardis E et al. J.Natl.Cancer Inst. 2005, 97, 724-732

  15. Thyroid irradiation • The risk to develop thyroid cancer after irradiation in individual who previously consumed stable iodine after an exposure to 1 Gy is reduced 5 fold • Low level of iodine in the soil is correlated with a 3 fold increase of risk to develop cancer compared with residents in areas with naturally more iodine in soil • At doses of contamination between 1.5-2 Gy there is no linear correlation between exposure and risk of cancer • Previously ingestion of iodine reduces radioactive iodine intake • Increased iodine supply reduces thyroid volume and multiplication of thyroid cell and risk of occurrence of mutations Cardis E et al. J.Natl.Cancer Inst. 2005, 97, 724-732

  16. Cardis E et al. J.Natl.Cancer Inst. 2005, 97, 724-732

  17. Cardis E et al. J.Natl.Cancer Inst.2005, 97, 724-732

  18. Thyroid irradiation • 1986-1995 in Bellarus 472 patients among which 97.7 were differentiated cancers • median age: les than 14 years • median age at exposure: 4.4 in children and 8.9 in adolescents • Italy and France after Chernobyl: 369 patients • Mean age in children more than 14 years • Follicular cancer: 15.2 % compared with 5.3 % in Bellarus • Most effected children were exposed at less than 5 years1 • Most cancers occur 5-30 years after irradiation but the risk last to 50 years2 Pacini F. et al. J.Clin.Endocrinol.Metab. 1997, 82, 3563-3569 Greenspan FS JAMA 1977, 237, 2089-2091

  19. Thyroid irradiation • Differences among cancers developed after Chernobyl and those developed in Italy1 • Extrathyroidal extension: 49.1% vs 24.9 % • Lymph node involvement: 64% vs 53.9 % • Distant metastasis: 7.8 % vs 17.3 % • For more latent forms of papillary cancer a new pick of incidence may be expected • 20 years after Chernobyl accident 5000 cases of thyroid cancer were diagnosed. 60-70 % had N1 and 10-15 had M12 1. Pacini F. et al. J.Clin.Endocrinol.Metab. 1997, 82, 3563-3569 2. Tuttle RM et al. Clin.Oncolocy 2011, 23, 268-275

  20. Relationship between the degree of iodine contamination and number and percentage of new cases of thyroid cancer in children and adolescents after Chernobyl nuclear reactor accident Pacini F et al. J.clin.Endocrinol.Metab. 1997, 82, 3563-3569

  21. Pacini F et al. J.clin.Endocrinol.Metab. 1997, 82, 3563-3569

  22. Iodine deficiency may play a role in the development of follicular cancer and may favor the development of anaplastic carcinoma

  23. Iodine and thyroid cancer • The relationship between thyroid cancer and dietary iodine is controversial • There are some data that could demonstrate that iodine deficiency may increase thyroid cancer in some areas • Iodine may act as adjuvant factor for carcinogensis and may have a role in the hystological profile of thyroid cancer • Is obvious from all statistics that increased dietary iodine is associated with an increase of incidence of thyroid cancer1 • Sicilia: • Thyroid malignancies: IDA – 2.96%, ISA 5.48 % • Follicular cancer: IDA; up to 127/105, • Anaplastic cancer: 93/105 • Knobel M et al. Arq.Bras. Endocrinol.Metab. 2007, 51, 701-712 • Belfiore A et al. Cancer 1987, 60, 3096-3192

  24. Iodine and thyroid cancer Iodine deficiency is associated with a relative risk (RR) of cancer as follows (Sweden)1 • 0.92 for all histological types • 0.80 for papillary cancer • 0.87 for anaplastic carcinma • 1.98 for follicular cancer The risk for follicular cancer is 1.3-15 in iodine deficient areas and depends of the time of residence in these areas2 • Petterson B et al. Int.J.Cancer 1996, 65, 13-19 • Galanti MR et al. Int J.Cancer 1995, 61, 615-621

  25. Iodine and thyroid cancer Frequency of thyroid cancer by tumor type in Salta, Argentina before and after iodine prophylaxis Harach C et al. Clin.Endocrinol. 1995, 61, 615-621

  26. Iodine and thyroid cancer Histologic pattern of thyroid tumors in two areas of Sicily, Italy with low and adequate iodine intake Belfiore A et al. Cancer 1987, 60, 3096-3102

  27. Iodine prophylaxis and thyroid cancer Incidence of different forms of thyroid cancer before and after iodine prophylaxis Papillary: pre prophylaxis 44% vs post prophylaxis: 60 % Papillary/follicular ratio: 1.7/1 to 3.1/1 1 Ratio papillary to follicular cancer according to iodine intake2 IDA: 0.1/1, moderate intake: 1.6/1-3.7/1, high intake: 3.4/1-6.5/1 1986-1999: 1500 new cases: Incidence: 3.86 to 6.08/105 After prophylaxis: papillary to follicular ratio: 5.323 • Harach H et al. Endocr.Pathiol. 2002, 13, 175-181 • Lind p et al. Thyroid 1998, 8, 1179-1183 • Szybinski Z et al. Wiad Lek 2001, 54, 106-116

  28. Iodine prophylaxis and thyroid cancer Incidence of different forms of thyroid cancer before and after iodine prophylaxis 1974-1976 and 1992-1994 • Increased percentage of thyroid cancer on thyroidectomies • Papillary: 54.3 % • Follicular: 27 % • Anaplastic: 11.1 % • Medullary: 4.6 % Papillary to follicular ratio: 1974-1976: 0.60 1992-1994: 6.88 Deandrea M et al. J.Endocriol.Invest. 1997, 20, 52-58

  29. Iodine prophylaxis and thyroid cancer iodine prophylaxis: • Increased incidence of papillary cancer • Decreased incidence of follicular cancer • Decreased incidence of anaplastic cancer • Improved prognosis

  30. Histology of thyroid cancer in iodine deficient areas (Algeria) Improvement of socio-econimc status from 1966-1981 and 1982-1991 Bakiri et all.Cancer 1998, 82, 1146-1153

  31. Bakiri et all.Cancer 1998, 82, 1146-1153

  32. Histological profileof thyroid cancers in an iodine sufficient area ( Connecticut - USA ) Schottenfeld D, Gersman ST. Epidemiology of thyroid Cancer 2008

  33. There is a trend to increase the incidence of thyroid cancer as well as an increase of papillary thyroid cancer Burges JR et al.J.Clin. Endocrinol.Metab.2000, 85, 4, 1513-1517

  34. Histology and age are the best predictor factors for survival Scheiden P et al.BMC Cancer 2006, 6, 102-106 5 years survival: • Papillary: 96 % • Follicular: 88.9 % • Medullary: 90.9 % Hundahl Sa et al. Cancer 1998, 83, 2638-2648 10 years survival: • Papillary: 93 % • Follicular: 85 % • Hurthle cell: 76 % • Medullary: 75 % • Anaplastic: 14 %

  35. Histology and age are the best predictor factors for survival Passler G et all.Endocrine-Related Cancer 2004,11, 131-139

  36. Radioactive elements release after CHERNOBYL 1986

  37. CONTAMINAREA RADIOACTIVA DUPA CERNOBIL 1986 - ROMANIA What happened in Romania? It partially remains in the area of suppositions

  38. RET/PTC in the key mutation seen in radiation-induced thyroid cancer and activation of BRAF is associated with sporadic forms of differentiated thyroid carcinoma Xing s et al Endocrine reviews 2007, 28, 742-762

  39. Data from literature • Elisei has demonstrated that clinical and histological profile of thyroid cancers was modified during the last 35 years through: • Increased incidence of papillary cancers from 80,5 % to 91% during these years • Decreased follicular cancers from 19,5 % to 9 %; • Increased incidence of cancer with diameter of less than 1 cm. from 7,9% in the firs half of the interval to 28,7 % in the second • Reduced incidence of macro-invasive cancers from 7 % to 1,9 %; • Reduced incidence of cancers with distant metastases from 5,4 la 2 %; • Reduced incidence of cases with lymph node metastases from 34,2 % to 22, 4%; • Reduced incidence of cases in advanced stages according to TNM VI, for stage III 10,8 to 7,4 % and for stage IV from 4,2% to 1,7 %. Elisei R., et all.J.Clin. Endocrinol.Metab. 2010,

  40. MATHERIAL AND METHOD • Data from files of patients with thyroid tumors submitted to surgery between 1975-2009 (35 years) were divided into 5 years intervals and analyzed for: • New cases for each interval • Histology • Clinical appearance • Stage of the disease according to TNM classification and tumor stage grouping TNM VI • Ratio between papillary and follicular cancer as indirect signs for the role of supposed external irradiation and modification due to iodine prophylaxis

  41. MATHERIAL AND METHOD • From 1981 most patients were assessed based on fine needle biopsy performed within the Department of Endocrinology of our hospital • Our data were compared with data from the Department of Endocrinology analyzed between 1971 and 2000 for patients admitted in this setting including those operated in other surgery clinics

  42. Algorithm of diagnosis for thyroid nodules used after 1981 in theClinic of Endocriology IASI THYROID NODULE CYST ULTRASOUND SOLID OR MIXED LESSION FNB BENIGN ABC SCINITIGRAPHY FOLLICULAR NEOPLASM MALIGN EVACUAATION, SCLEROZING WARM COLD T4 SOLVED LOW RISK HIGH RISK RECURRENCE THIROIDECTOMY FOLLOW-UP E.Zbranca et.al.Symp.Nat.Endocrinol.1995, Endocrinologie Clinica 1997

  43. EPIDEMIOLOGICAL BACKGROUND Moldova is situated in the northern part of Romania Different studies provided data that show a decrease of prevalence of goiter and a mild to moderate iodine deficiency assessed by urinary iodine determination, except for same areas where urinary iodine is still low

  44. Demographic data of patients with thyroid tumors admitted in the Ist Surgery Clinic of Iasi

  45. RESULTS: thyroid tumors submitted to surgery between 1975-2009 in the 1st Surgery Clinic of Iasi-345 cases

  46. WHAY WE FOCUSED OUR RESEARCH ON CHANGES OF HYSTOLOGICAL PROFILE OF TUMORS DURING TIME? • Histology, age and stage at diagnosis are the best predictive prognostic factors for thyroid cancers • All these factors are influenced by at least two major events that happen in Romania: • Hypothetical external irradiation after Chernobyl with increase of papillary forms • Important modification of iodine supply due to active and universal salt iodination also with increase of papillary form and decrease of incidence of goiter that may mask a carcinoma

  47. Survival in thyroid cancers acording to histologyClinic of Endocirnology Iasi 1993

  48. Survival in thyroid cancers acording to age at diagnosisClinic of Endocrinology Iasi

  49. Survival in thyroid cancers acording to tumor stagingClinic of Endocirnology Iasi

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