THYROID CANCER INCIDENCE CONTINUES TO RISE BUT MORTALITY REMAINS STABLE IN YOUNG, HISPANIC AND BLACK POPULATIONS IN THE UNITED STATES

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1 ENDOCRINE PRACTICE Rapid Electronic Article in Press Rapid Electronic Articles in Press are preprinted manuscripts that have been reviewed and accepted for publication, but have yet to be edited, typeset and finalized. This version of the manuscript will be replaced with the final, published version after it has been published in the print edition of the journal. The final, published version may differ from this proof. Letter to the Editor EP THYROID CANCER INCIDENCE CONTINUES TO RISE BUT MORTALITY REMAINS STABLE IN YOUNG, HISPANIC AND BLACK POPULATIONS IN THE UNITED STATES Anupam Kotwal MBBS1, Archie Bleyer MD FRCP2, Juan P. Brito MD MSc1 Running title: Thyroid cancer trends From: 1 Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, Rochester, MN, 55905; 2 Department of Radiation Medicine, Oregon Health and Science University, Portland, OR, Corresponding author: Juan P. Brito MD MSc Division of Endocrinology, Diabetes, Metabolism and Nutrition Knowledge and Evaluation Research Unit in Endocrinology (KER_Endo) Mayo Clinic 200 1st Street SW, Rochester, MN brito.juan@mayo.edu

2 To the editor, Thyroid cancer incidence trend in the U.S. appears to be plateauing since 2009 (1). We evaluated annual percent change (APC) in age-adjusted thyroid cancer incidence and mortality rates across age, sex and self-identified racial/ethnic subgroups from in the Surveillance, Epidemiology and End Results (SEER) 18 database using software SEER*Explorer (2). Joinpoint analysis on CDC-WONDER database (3) was performed for data unavailable from SEER. A positive APC meant increasing rate, negative APC meant decreasing rate, and change in the value of APC implied trend change. A 95% confidence interval (CI) not containing 0 and p value < 0.05 implied significant trend change. APC in incidence rate from was 6.7 and from was 2.2; APC in mortality rate from was 0.6. From 2000 to 2014, in Hispanics and Blacks, APC in incidence rates was 4.7 and 5.2 respectively, while that in non-hispanic whites was 7.2 before 2009 and 1.9 after 2009 (Figure 1A). From , in Hispanics and blacks, APC in mortality rates was 0.1 and 0.7 respectively, and that in non-hispanic whites was 0.5 (Figure 1A). APC in incidence rates and mortality rates in different age groups are mentioned in Figure 1B and 1C respectively.. After 2009, females and males had APC in incidence rate of 2.1 and 2.5, respectively. APC in mortality rate was 0.4 for females and 1 for males. Upon combining these subgroups, Hispanic females years of age had APC in incidence rate of 4.9 without any deceleration after 2009, (Figure 1D) and stable mortality rates from CDC WONDER data. Non-Hispanic white females >75 years of age had APC in incidence rate of 6.7 before 2009 and after 2009, with mortality rate APC of 0.4 (Figure 1D).

3 Incidence trend deceleration mainly occurred in non-hispanic Whites and elderly, but not in young, Hispanic and black subgroups. Even though incidence increased at a faster rate in young, Hispanic and black subgroups, mortality rates remained fairly stable in these subgroups, suggesting diagnosis of predominantly low-risk thyroid cancer likely due to increased detection rates. In comparison, non-hispanic whites and elderly demonstrated a small but continuous increase in mortality rates. Hispanic females years of age had the highest incidence trend change without any deceleration after 2009 and stable mortality rates, whereas non-hispanic white females >75 years of age had a decrease in incidence rate but stable mortality rate. The rising thyroid cancer incidence trends despite stable mortality trends in Hispanic, black and young subgroups after 2009 may suggest a shift in the paradigm of overdiagnosis. More research is needed to understand whether the small increase in thyroid cancer mortality rates in non-hispanic whites elderly is due to increased diagnosis of clinically significant thyroid cancer versus attribution bias (misclassification of thyroid cancer related deaths) or treatment related deaths. Acknowledgements The abstract of this study was presented at Endocrine Society s 100th Annual Meeting and Expo in Chicago, IL and published in Endocrine Reviews. 2018;39(2). References 1. Morris LGT, Tuttle RM, Davies L. Changing Trends in the Incidence of Thyroid Cancer in the United States. JAMA otolaryngology-- head & neck surgery. 2016;142:

4 2. SEER*Explorer: An interactive website for SEER cancer statistics [Internet]. Beta Version. Surveillance Research Program, National Cancer Institute [Internet] Available from: SEER*Explorer: An interactive website for SEER cancer statistics [Internet]. Beta Version. Surveillance Research Program, National Cancer Institute. 3. United States Department of Health and Human Services (US DHHS), Centers for Disease Control and Prevention (CDC), National Center for Health Statistics (NCHS), Underlying Cause of Death on CDC WONDER Online Database, released Data are compiled from data provided by the 57 vital statistics jurisdictions through the Vital Statistics Cooperative Program. Figure Legend Figure 1A: Annual age-adjusted thyroid cancer incidence rates and mortality rates per 100,000 along with APC values, their 95% confidence intervals and p values separated by race/ethnicity. Figure 1B: Annual age-adjusted thyroid cancer incidence rates per 100,000 along with APC values, their 95% confidence intervals and p values by separated by age groups. Figure 1C: Annual age-adjusted thyroid cancer mortality rates per 100,000 along with APC values, their 95% confidence intervals and p values by separated by age groups. Figure D: Annual age-adjusted thyroid cancer incidence and mortality rates per 100,000 along with APC values, their 95% confidence intervals and p values upon combining age, sex and racial subgroups.

5 0.1 (-0.6, 0.8); p= (0.2, 0.9); p< (-0.5, 1.9); p=0.2 Panel A Panel B Panel C Panel D