1. Thyroid Cancer Incidence in Massachusetts, 1984-2003 Richard Knowlton, MS Annie MacMillan, MPH Massachusetts Cancer Registry Massachusetts Department of Public Health

2. The Thyroid Gland Located in the middle of the lower neck, below the larynx (voice box) and just above your clavicles (collarbones). It is shaped like a "bow tie," having two halves (lobes): a right lobe and a left lobe joined by an "isthmus.“ Located in the middle of the lower neck, below the larynx (voice box) and just above your clavicles (collarbones). It is shaped like a "bow tie," having two halves (lobes): a right lobe and a left lobe joined by an "isthmus.“ One of the endocrine glands, which make hormones to regulate physiological functions in your body. It manufactures thyroid hormone, which regulates the rate at which the body carries on its functions. One of the endocrine glands, which make hormones to regulate physiological functions in your body. It manufactures thyroid hormone, which regulates the rate at which the body carries on its functions. Contains only two types of epithelial cells: the follicular cell, which makes and stores thyroid hormone and the parafollicular or C cell, which makes calcitonin, a regulator of the body’s calcium metabolism. Contains only two types of epithelial cells: the follicular cell, which makes and stores thyroid hormone and the parafollicular or C cell, which makes calcitonin, a regulator of the body’s calcium metabolism. Follicular cell Parafollicular (C) cell Left LobeRight Lobe Isthmus

3. Types of Thyroid Cancer Papillary: Papillary: –Malignant epithelial tumor with follicular cell differentiation. –Most common, accounting for 70% of thyroid cancers. –Peak onset age between 30 and 50, with the female to male ratio being 3:1. –Overall cure rate is very high (near 100% for small lesions in young patients). Follicular: Follicular: –Malignant epithelial tumor with follicular cell differentiation. –Accounts for about 15% of thyroid cancers. –Peak onset age between 40 and 60, with female to male ratio being 3:1. –Overall cure rate high (near 95% for small lesions in young patients). Source: EndocrineWeb.com (www.endocrineweb.com)

4. Types of Thyroid Cancer (continued) Medullary: Medullary: –Malignant tumor with parafollicular cell differentiation. –Accounts for about 5-8% of thyroid cancers. –About 20% of medullary cancers result from inheriting an abnormal gene. –Overall 10 year survival rates are 90% for local disease, 70% for regional spread and 20% for distant spread. Anaplastic: Anaplastic: –Highly malignant tumor, partially or totally undifferentiated. –Least common (0.5-1.5%) and most deadly of all the thyroid cancers, with most patients dying within a year of diagnosis. –Most of these cancers are so aggressively attached to vital neck structures that they are inoperable at the time of diagnosis. Source: EndocrineWeb.com (www.endocrineweb.com)

5. Thyroid Cancer in Massachusetts From 1999-2003, thyroid cancer was ranked #8 for women with a rate of 14.3/100,000, much lower than breast (141.3), lung (62.0) and colorectal (50.9). From 1999-2003, thyroid cancer was ranked #8 for women with a rate of 14.3/100,000, much lower than breast (141.3), lung (62.0) and colorectal (50.9). For the same period, the rate for men was 4.8/100,000, much lower than prostate (185.1), lung (89.1) and colorectal (72.2). For the same period, the rate for men was 4.8/100,000, much lower than prostate (185.1), lung (89.1) and colorectal (72.2). Despite its status as a rarer cancer, the rates have increased from 1999-2003 by 81% for women (10.7 to 18.7) and 66% for men (3.8 to 6.3), the greatest rate increases among ALL cancers for men and women. Despite its status as a rarer cancer, the rates have increased from 1999-2003 by 81% for women (10.7 to 18.7) and 66% for men (3.8 to 6.3), the greatest rate increases among ALL cancers for men and women.

6. Thyroid Cancer Studies There has been a worldwide increase in thyroid cancer over the past two decades, particularly the papillary form. There has been a worldwide increase in thyroid cancer over the past two decades, particularly the papillary form. MCR wanted to compare rates observed in Massachusetts with other studies to see if the patterns of increase were similar to what has been reported elsewhere. MCR wanted to compare rates observed in Massachusetts with other studies to see if the patterns of increase were similar to what has been reported elsewhere.

7. Annual Age-adjusted Thyroid Cancer Incidence Rates for Males and Females Massachusetts vs SEER 1984-2003 Rates are age-adjusted to the 2000 U.S. Standard Population

8. Age Adjusted Thyroid Cancer Rates by Race/Ethnicity 1999-2003

9. Age-specific Thyroid Cancer Incidence Rates for Males and Females, Massachusetts, 1999-2003 Rates are age-adjusted to the 2000 U.S. Standard Population

10. Thyroid Cancer Histological Types, 1984-2003 Massachusetts Cancer Registry Data

11. Age-adjusted Incidence Rates of Thyroid Cancer by Histologic Type, 1984-2003, Massachusetts Rates are age-adjusted to the 2000 U.S. Standard Population

12. The Influence of Papillary Cancer on Overall Thyroid Cancer Rates When comparing 1984 thyroid cancer numbers with those of 2003, papillary cancer numbers accounted for 95% of the increase, a significant difference compared with follicular, medullary and anaplastic cases. When comparing 1984 thyroid cancer numbers with those of 2003, papillary cancer numbers accounted for 95% of the increase, a significant difference compared with follicular, medullary and anaplastic cases. Type 1984 Number 2003 Number Difference % of Diff p-value* Total190829639 Papillary12072760795% <.0001 <.0001 Follicular4367244%.45 Medullary152271%.81 Anaplastic12131<1% *-compares with type directly below it.

13. Papillary Thyroid Cancer Rates 1984-2003 Joinpoint Analysis APC1=6.48 APC2=14.26 1997

14. Possible Reasons for the Increase in Papillary Thyroid Cancer Cases History of head or neck radiation among children or exposure to nuclear fallout during the 1950s ? History of head or neck radiation among children or exposure to nuclear fallout during the 1950s ? Radiation in children for the treatment of such conditions as head lice, enlarged thymus, enlarged tonsils and enlarged lymph nodes, which lasted from around 1940 to around 1960, has been associated with thyroid cancer. Radiation in children for the treatment of such conditions as head lice, enlarged thymus, enlarged tonsils and enlarged lymph nodes, which lasted from around 1940 to around 1960, has been associated with thyroid cancer. Ground nuclear tests in the 1950s exposed children to radiation in the western part of the USA, particularly Nevada. There is not a consensus of opinion on this as a cause for thyroid cancer as the nuclear exposure was much less than that received by survivors of Hiroshima and Nagasaki and Chernobyl who had a significant risk of developing thyroid cancer. Ground nuclear tests in the 1950s exposed children to radiation in the western part of the USA, particularly Nevada. There is not a consensus of opinion on this as a cause for thyroid cancer as the nuclear exposure was much less than that received by survivors of Hiroshima and Nagasaki and Chernobyl who had a significant risk of developing thyroid cancer.

15. Better Detection A recent study published by JAMA linked the increasing incidence in the USA to better detection of smaller (<1cm) thyroid cancers. The introduction of fine needle aspiration biopsy (FNAB) and ultrasound (US) has aided in these earlier detections. Other studies have mirrored these findings. A recent study published by JAMA linked the increasing incidence in the USA to better detection of smaller (<1cm) thyroid cancers. The introduction of fine needle aspiration biopsy (FNAB) and ultrasound (US) has aided in these earlier detections. Other studies have mirrored these findings. (source: ‘Increasing Incidence of Thyroid Cancer in the United States, 1973-2002’, JAMA, May 10, 2006.)

16. Autopsy Findings The increase of papillary thyroid cancer cases by better detection is supported by autopsy studies: In 1947, the New England Journal of Medicine reported that thyroid cancer, particularly papillary, was a common autopsy finding, despite its never having caused symptoms during a person’s life. In 1947, the New England Journal of Medicine reported that thyroid cancer, particularly papillary, was a common autopsy finding, despite its never having caused symptoms during a person’s life. In 1985, Cancer reported on a study in which 36% of autopsy cases not known to have had thyroid cancer during their lives nonetheless had 1 or more foci of thyroid cancer. In 1985, Cancer reported on a study in which 36% of autopsy cases not known to have had thyroid cancer during their lives nonetheless had 1 or more foci of thyroid cancer. (Source: ‘Increasing Incidence of Thyroid Cancer in the United States, 1973- 2002’, JAMA, May 10, 2006.)

17. Trends in Papillary Tumor Size 1995-2003 Rates are age-adjusted to the 2000 U.S. Standard Population

18. The Size of Papillary Tumors 1995 v. 2003 When comparing the sizes of papillary tumors in 1995 with those in 2003, tumors 1 cm or less accounted for 41% of the increase and those 2 cm or less accounted for 71% of the increase. The increase for the smallest tumors was significant when compared with the larger ones. When comparing the sizes of papillary tumors in 1995 with those in 2003, tumors 1 cm or less accounted for 41% of the increase and those 2 cm or less accounted for 71% of the increase. The increase for the smallest tumors was significant when compared with the larger ones. Tumor Size 19952003Difference % of Diff p-value* All Sizes 241672431 1 cm or less 6624117541%<.05 1.1-2 cm 7820913130%.40 2.1-5 cm 8319711426%<.001 > 5 cm 1425113% *-compares with tumor size directly below it.

19. Papillary Thyroid Microcarcinomas Thyroid carcinomas less than 1 cm are almost exclusively papillary and are termed papillary thyroid microcarcinoma (PTMC) according the World Health Organization. Thyroid carcinomas less than 1 cm are almost exclusively papillary and are termed papillary thyroid microcarcinoma (PTMC) according the World Health Organization. (source:’Clinical and Histological Characteristics of Papillary Thyroid Microcarcinoma: Results of a Retrospective Study in 243 Patients’, Journal of Clinical Endocrinology & Metabolism, 2006.) ------------------------------------------------------------------ Maybe the better detection of these microcarcinomas which are almost exclusively papillary cancers accounts for the rise in only papillary cancer cases.

20. Tumor Size Variation by Thyroid Cancer Type 1995-2003 0-1.0 cm 1.1-2.0 cm 2.1-5.0 cm> 5 cm

21. Mean Papillary Tumor Size (Cm) by Gender 1995-2003

22. Stage of Thyroid Cancer by Gender, 2001-2003 MalesFemales

23. Limitations of the Study The MCR database does not collect information on risk factors such as potential exposure to radiation. The MCR database does not collect information on risk factors such as potential exposure to radiation. Data were missing for 11% of all thyroid cancer cases for tumor size, with disproportionately higher distributions of missing tumor size data for the following: anaplastic cases, blacks, Hispanics and females. Data were missing for 11% of all thyroid cancer cases for tumor size, with disproportionately higher distributions of missing tumor size data for the following: anaplastic cases, blacks, Hispanics and females. No data on tumor size was available before 1995. No data on tumor size was available before 1995.

24. Findings Thyroid cancer rates in Massachusetts have increased from 3.4/100,000 in 1984 to 12.7/100,000 in 2003, a significant increase according to joinpoint analyses. Thyroid cancer rates in Massachusetts have increased from 3.4/100,000 in 1984 to 12.7/100,000 in 2003, a significant increase according to joinpoint analyses. 95% of this increase has been due to papillary cancers. 95% of this increase has been due to papillary cancers. 41% of the papillary cancer increase consisted of tumors 1 cm or less and 71% consisted of tumors 2 cm or less. 41% of the papillary cancer increase consisted of tumors 1 cm or less and 71% consisted of tumors 2 cm or less. The mean size of papillary tumors has been larger for males than females for the years 1995-2003. Additionally, males were diagnosed at significantly later stages from 2001-2003. The mean size of papillary tumors has been larger for males than females for the years 1995-2003. Additionally, males were diagnosed at significantly later stages from 2001-2003. For the four major racial/ethnic groups, the female to male ratio is 3:1 for thyroid cancer. For the four major racial/ethnic groups, the female to male ratio is 3:1 for thyroid cancer.

25. Conclusions The reason for the increases in thyroid cancer tumors 1 cm and less appear to be the result of better detection and the increase in the larger tumors between 1.1 and 5 cm suggest better clinician awareness of thyroid cancer as well. The reason for the increases in thyroid cancer tumors 1 cm and less appear to be the result of better detection and the increase in the larger tumors between 1.1 and 5 cm suggest better clinician awareness of thyroid cancer as well. If this is the case, the numbers of thyroid cancer cases should level off after a few more years to account for cases detected earlier than would have been the case without earlier detection procedures If this is the case, the numbers of thyroid cancer cases should level off after a few more years to account for cases detected earlier than would have been the case without earlier detection procedures If the numbers continue to increase, other factors will need to be further examined, such as environmental exposures, hormonal factors and genetics. If the numbers continue to increase, other factors will need to be further examined, such as environmental exposures, hormonal factors and genetics. The greater increase of papillary cases for females, the mean size of tumors being larger for males from 1995-2003 and the stage at diagnosis being significantly later for males from 2001- 2003 supports earlier detection among females who are utilizing the health care system more than males. The greater increase of papillary cases for females, the mean size of tumors being larger for males from 1995-2003 and the stage at diagnosis being significantly later for males from 2001- 2003 supports earlier detection among females who are utilizing the health care system more than males.

26. The Next Step The MCR will be publishing a fact sheet on thyroid cancer in Massachusetts in June of 2007. The MCR will be publishing a fact sheet on thyroid cancer in Massachusetts in June of 2007. Further analyses will include the rates of second primary cancers among people with thyroid cancer. Further analyses will include the rates of second primary cancers among people with thyroid cancer.