The Rising Incidence Of Small Endocrine Cancers In The United States: Effects On Surgical Therapy In An Age Of Imaging

The Rising Incidence of Small Endocrine Cancers in the United States: Effects on Surgical Therapy in an Age of Imaging Eric J. Kuo, Ronald R. Salem, Sanziana A. Roman, Julie A. Sosa, Department of Surgery, Yale School of Medicine, New Haven, CT, Department of Surgery, Duke University School of Medicine, Durham, NC The increasing utilization of imaging technology has led to the diagnosis of cancers earlier in their clinical course. When small tumor size is coupled with relatively indolent histology, excellent oncologic outcomes require the risks of surgery to be carefully considered. However, characteristics and outcomes of small cancers of the thyroid and endocrine pancreas remain poorly defined, and evidence to guide their management is sparse. Patients with tall cell (mTCV) and diffuse sclerosing (mDSV) variants of papillary thyroid microcarcinoma (mPTC), follicular (mFTC) and Hurthle cell microcarcinoma (mHCC), parathyroid carcinoma (PC) and pancreatic neuroendocrine tumors (PNETs) ≤ 2 cm in size were selected from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database, 1988-2009. Data regarding incidence, characteristics, and outcomes were extracted and analyzed with χ tests, ANOVA, the Kaplan Meier method, log-rank tests, and Cox proportional hazards. 97 mTCV, 90 mDSV, 371 mFTC, 193 mHCC, and 263 PNETs ≤ 2 cm were identified. The incidence of mTCV, mDSV, and mFTC remained stable throughout the study period, while the incidences of mHCC and PNETs ≤ 2 cm increased by 400% and 710% over the study period, respectively. Although survival was similar, mTCV and mDSV were associated with higher rates of extrathyroidal extension and nodal metastasis in comparison to classic mPTC. mFHCC had over eight times the rate of distant metastases compared to mPTC and was associated with compromised 10-year disease specific survival (95.4 vs. 99.3%, P<0.001). Rates of extrapancreatic extension, nodal metastasis, and distant metastasis in PNETs ≤ 2 cm were 17.9%, 27.3%, and 9.1%, respectively. The incidence of many endocrine cancers is increasing, presumably due to increased detection. All histologies studied were capable of exhibiting aggressive behavior despite small tumor size. Further studies that specifically examine the risks and benefits of surgical therapy in small tumors may clarify future surgical decision making. Acknowledgements I would like to thank my mentors, Dr. Ronald R. Salem, MB ChB, Dr. Sanziana A. Roman, MD, and Dr. Julie A. Sosa, MD, MA, whose invaluable guidance has made this thesis possible, and who have served as incredible role models both inside and out of the operating room. Also, I feel grateful to Dr. Robert Udelsman and the attendings of the Yale School of Medicine Department of Surgery for fostering my interest in a career in surgery. I would also like to thank my fellow residents of Farnam Memorial Building Room 116, Michelle Chen, Paolo Goffredo, Stephanie Wood, and Hasly Harsono, for your helpful insights and for making my year in research truly memorable. I am also indebted to Dr. John Forrest and staff at the Yale School of Medicine Office of Student Research, who has supported this research through generous contributions from the NIH-NCRR CTSA-TL-1 Medical Student Research Fellowship and Richard K. Gershon, M.D., Student Research Fellowship. Elements of the work presented in this thesis are currently published in Thyroid (aggressive variants of papillary thyroid microcarcinoma), Surgery (follicular and Hurthle cell microcarcinoma), and Annals of Surgical Oncology (pancreatic neuroendocrine tumors ≤ 2 cm). The abstract “Patients with follicular and Hurthle cell microcarcinomas have compromised survival: a population level study of 22,738 patients” was presented during a podium presentation American Association of Endocrine Surgeons (AAES) 2013 Annual Meeting on April 15, 2013, in Chicago, Illinois. TABLE OF CONTENTS INTRODUCTION 1 Thyroid cancer 2 Aggressive variants of papillary thyroid microcarcinoma 4 Follicular and Hurthle cell microcaricnoma 5 Pancreatic neuroendocrine tumors 6 METHODS 7 Data Source and Study Participants 7 Statistical Analysis 10 RESULTS 10 Aggressive variants of papillary thyroid microcarcinoma 10 Follicular and Hurthle cell microcarcinoma 18 Pancreatic neuroendocrine tumors ≤ 2 cm in size 28 DISCUSSION 35 Aggressive variants of papillary thyroid microcarcinoma 35 Follicular and Hurthle cell microcarcinoma 38 Pancreatic neuroendocrine tumors ≤ 2 cm 43 Conclusions 47 REFERENCES 48