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THYROID CANCER EVOLUTION OF THE DISEASE EVALUATED IN ONE SETTING VOICHIŢA MOGOŞ 1. EUGEN TIRCOVEANU 2 1. Clinic of Endocrinology, 1 st Surgery Clinici.

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Presentation on theme: "THYROID CANCER EVOLUTION OF THE DISEASE EVALUATED IN ONE SETTING VOICHIŢA MOGOŞ 1. EUGEN TIRCOVEANU 2 1. Clinic of Endocrinology, 1 st Surgery Clinici."— Presentation transcript:

1 THYROID CANCER EVOLUTION OF THE DISEASE EVALUATED IN ONE SETTING VOICHIŢA MOGOŞ 1. EUGEN TIRCOVEANU 2 1. Clinic of Endocrinology, 1 st Surgery Clinici University of Medicine and Pharmacy “Gr.T Popa” Iasi Histological profile of thyroid cancer between Chernobyl effect and universal iodine fortification of salt

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, Between : 2.4 times increase in thyroid cancer incidence All thyroid cancer: 3.6/10 5 to 8.7/10 5 /year (with 5.1/10 5 ) Papillary cancer: 2.7/10 5 to 7.7/10 5 /year Small papillary cancer account for 87 % of the cancer Mortality decreased from 0.57 to 0.47/10 5 /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,

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7 There was noticed a steady increase of thyroid cancer all over the world Schottenfeld D et al. CA Cancer J.Clin. 1978, 28, USA:Connecticut Tumor registry : 1.4/10 5 /year to : 4/10 5 /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: % –Japan: %

8 There was noticed a steady increase of thyroid cancer all over the world Scheiden P.et al. BMC Cancer 2006, 6, Evaluation in an European country – Luxembourg 30 years after Chernobyl in 2 cohorts: (a) and (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 8.6/10 5 /year Increased incidence in women from 7.4 to 10.1/10 5 /year Increased incidence in men from 2.3 to 3.6 /10 5 /year Mahoney MC et al. Int.Epidemiol. 2005, 34, ( ) Severe exposure: increase incidence in males + 775%, in females:+1925% Low exposure: increased incidence in males:+54 %, in females: %

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

10 There was noticed a steady increase of thyroid cancer all over the world Leehardt L et al. Thyroid 2004, 14, FRANCE: 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, Scotish Cancer Registry : Incresed incidence of thyroid cancer from 1.76 to 3.54/10 5 /year in women Increased incidence from 0.82 to 1.25/10 5 /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 ground 1 Belarus: cancer in children: 1/10 6 before and 100/10 6 after Chernobyl 2. The risk in children less than 1 year is 30 fold greater 3 Cardis E et al. J.Natl.Cancer Inst. 2005, 97, Nagatachi S et al. Thyroid 2002, 12, Boltze C et al. Oncology 2009, 22,

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 ( 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,

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 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,

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18 Thyroid irradiation Pacini F. et al. J.Clin.Endocrinol.Metab. 1997, 82, Greenspan FS JAMA 1977, 237, 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 years 1 Most cancers occur 5-30 years after irradiation but the risk last to 50 years 2

19 Thyroid irradiation 1. Pacini F. et al. J.Clin.Endocrinol.Metab. 1997, 82, Tuttle RM et al. Clin.Oncolocy 2011, 23, Differences among cancers developed after Chernobyl and those developed in Italy 1 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 % had N1 and had M1 2

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,

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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 cancer 1 Sicilia: –Thyroid malignancies: IDA – 2.96%, ISA 5.48 % –Follicular cancer: IDA; up to 127/10 5, –Anaplastic cancer: 93/ Knobel M et al. Arq.Bras. Endocrinol.Metab. 2007, 51, Belfiore A et al. Cancer 1987, 60,

24 Iodine and thyroid cancer Iodine deficiency is associated with a relative risk (RR) of cancer as follows (Sweden) 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 in iodine deficient areas and depends of the time of residence in these areas 2 1.Petterson B et al. Int.J.Cancer 1996, 65, Galanti MR et al. Int J.Cancer 1995, 61,

25 Iodine and thyroid cancer Frequency of thyroid cancer by tumor type in Salta, Argentina before and after iodine prophylaxis Total number of casesYears after iodine prophylaxis 10 years Papillary26 46 Follicular15 Anaplastic9 13 Ratio between Papillary and follicular cancer Harach C et al. Clin.Endocrinol. 1995, 61,

26 Iodine and thyroid cancer Histologic pattern of thyroid tumors in two areas of Sicily, Italy with low and adequate iodine intake Total number of cases submitted to surgery Low intake High intake 911(126) 2437 (419) Papillary Follicular11 27 Anaplastic5 9 Belfiore A et al. Cancer 1987, 60,

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 intake 2 IDA: 0.1/1, moderate intake: 1.6/1-3.7/1, high intake: 3.4/1-6.5/ : 1500 new cases: Incidence: 3.86 to 6.08/105 After prophylaxis: papillary to follicular ratio: Harach H et al. Endocr.Pathiol. 2002, 13, Lind p et al. Thyroid 1998, 8, Szybinski Z et al. Wiad Lek 2001, 54,

28 Iodine prophylaxis and thyroid cancer Incidence of different forms of thyroid cancer before and after iodine prophylaxis and Increased percentage of thyroid cancer on thyroidectomies Papillary: 54.3 % Follicular: 27 % Anaplastic: 11.1 % Medullary: 4.6 % Papillary to follicular ratio: : : 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 Bakiri et all.Cancer 1998, 82, Histology of thyroid cancer in iodine deficient areas (Algeria) Improvement of socio-econimc status from and

31 Bakiri et all.Cancer 1998, 82,

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

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

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

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

36 Radioactive elements release after CHERNOBYL 1986

37 CONTAMINAREA RADIOACTIVA DUPA CERNOBIL 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,

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 (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 the Clinic of Endocriology IASI THYROID NODULE ULTRASOUNDCYSTSOLID OR MIXED LESSION FNB MALIGN FOLLICULAR NEOPLASM SCINITIGRAPHY COLDWARM LOW RISKHIGH RISK THIROIDECTOMY FOLLOW-UP ABC BENIGN T4 EVACUAATION, SCLEROZING RECURREN CE SOLVED 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 UrinaryGoiter % COUNTY Iodine  g/dL Thyroid ultrasound examination Suceava Botosani Neamt< Iasi

44 IntervalNumber of cases AgeFemalesMales ± ± ± ± ± ± ± ± Demographic data of patients with thyroid tumors admitted in the I st Surgery Clinic of Iasi

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

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47 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

48 Survival in thyroid cancers acording to histology Clinic of Endocirnology Iasi 1993

49 Survival in thyroid cancers acording to age at diagnosis Clinic of Endocrinology Iasi

50 Survival in thyroid cancers acording to tumor staging Clinic of Endocirnology Iasi

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52 Taking into account only cancers derived from follicular epithelium the percentage of papillary and follicular cancers in more obvious among al tumors

53 Histological profile of thyroid tumors in the Clinic of Endocrinology of Iasi %

54 Expectation after external irradiation and improved iodine supply Increased incidence of papillary carcinomas in younger age, but the risk after exposure persists long life after exposure Increased incidence of aggressive forms in children and young adult immediately after irradiation Normal iodine intake is associated also with increase of papillary cancers with good prognosis even in advanced forms and increased papillary to follicular ratio Decrease incidence of follicular cancer with a less good prognosis Decrease incidence of anaplastic carcinoma Diagnosis made in less advanced stages of the disease

55 Interval Papillary Pap/fol Follicular Foll less dif MTC Anaplastic Striking features noticed during the analyzed interval: increase incidence of papillary cancers, decrease of follicular forms, decrease of anaplastic carcinomas – all seems to be related with a better iodine prophylaxis and perhaps to external irradiation due to Tchernobil accident

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57 NEW CASES OF THYROID CANCER 1971 – 2000 CLINIC OF ENDOCRINOLOGY IASI

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59 Interval Unilateral tumor Bilateral tumor Lymph node involvement Developed on goiter The trend of thyroid cancer derived from follicular epithelium during 35 years is a slightly reduce of tumors diagnosed in later stages : bilateral, with lymph node involvement. Only in the last 5 years the histology did not reveal surroundings of goiter in the proximity of tumors due to active iodine prophylaxis

60 Interval micro carcinoma T I T II T III T IV Tumor staging at time of diagnosis show that after 1990 there were discovered microcarcinomas, stage I tumors increase and stage IV tumors obviously decrease (TNM classification VI)

61 Interval TI T II T III T IV Grouping of tumor stage according to histology, tumor extension and age at diagnosis show that after 1990 slightly more tumors were discovered in less advanced stages even through the mean age at diagnosis does not change during the analyzed interval (TNM classification VI)

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64 EVOLUTION of RATIO BETWEEN PAPILLARY AND FOLLICULAR CANCER 1971 – 2000 Clinic of Endocrinology Iasi (309 cases) Lind P. 1998: this ratio depends of iodine supply 6,5/1 - 3,8 /1: increased iodine supply; 3,7/1 - 1,6/1: moderate iodine supply 1,6/1 - 1,19/1 iodine deficiency

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66 CONCLUSIONS Our data on patients with thyroid cancers analyzed over a period of 35 years indicate that: It is an important increase in each 5 years interval, of number of new cases There is an important increase of papillary cancer and the ratio between papillary and follicular cancer and a decrease of anaplastic carcinoma There is increase of cases discovered in earlier stages of the disease We cannot assume that this events are due to the external irradiation because of lack of genetic and clinical evidence We believe that the afore mentioned evolution of histological profile of thyroid cancer in our setting is due to a better iodine prophylaxis


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