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BACKGROUND

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It was not until the 19th century that Billroth, Kocher, Halsted, and others refined the thyroidectomy operation into a standard treatment for thyroid cancer with advancements in anti-septic technique, anesthesia, recurrent laryngeal nerve protection, and parathyroid preservation.1,2 In the first half of the 20th century, oncologic resection for papillary thyroid cancer (PTC) commonly incorporated a “block dissection,” which sacrificed the sternocleidomastoid muscle, spinal accessory nerve, and marginal mandibular branch of the facial nerve resulting in significant deformity. George Crile Jr. heralded a more limited dissection with successful oncologic outcomes, which sparked the on-going debates regarding extent of dissection, implications of neck metastases, and prognostic factors for risk stratification.3 As early detection of PTC increased by the 1980s with the widespread use of diagnostic ultrasound and fine needle aspiration biopsy, controversy regarding the management of smaller tumors grew. Furthermore, with the development of radioactive iodine as a successful adjuvant therapy, there has been considerable debate regarding specific indications for administration.4,5 Nevertheless, with these advancements, thyroid cancer has become a treatable disease and the stage has been set for development of modern-era treatments, particularly molecular-based targeted therapeutics.

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EPIDEMIOLOGY

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Thyroid cancer is the most common endocrine malignancy accounting for over 60,000 new cases (3.6% of all cancer cases) diagnosed in 2013 in the United States.6 Its incidence has increased from 4.6 per 100,000 in 1975 to 11.6 per 100,000 in 2009, designating it as the fastest-growing cancer in recent years. However, the mortality rate has remained constant at approximately 0.5 per 100,000 with an overall 5-year survival rate of 94.2%.7

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The increase in thyroid cancer is nearly completely attributable to papillary thyroid cancer (PTC). There has been a 2.9-fold increase of PTC over the past three decades, without a significant change in the incidence of follicular, medullary, or anaplastic tumors.8 PTC rates were also noted to increase most rapidly among females, rising nearly 100% in both the White non-Hispanic and Black populations.9 Furthermore, the highest rate of increase was for tumors smaller than 1 cm, accounting for 49% of the increased incidence of tumors between 1998 and 2002 with an annual percent change of 8.6% for men and 9.9% for women.8,10 These overall trends, along with the unchanged PTC mortality rate, may suggest there has been increased detection of smaller tumors.

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The growth in incidence is largely attributable to increased utilization and improvement of highly sensitive imaging modalities. Accordingly, the use of thyroid fine needle aspiration biopsy (FNA) has more than doubled from 2006 to 2011.11 Considering that approximately 6% to 36% of the population have occult thyroid tumors upon autopsy and ultrasounds are able to detect lesions as small as 2 mm, it is reasonable to assume that the increased detection of occult tumors has led to the increased incidence.12-14 However, while there ...

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