NCCN Categories of Evidence and Consensus
Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate.
Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate.
All recommendations are category 2A unless otherwise noted.
Clinical trials: NCCN believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
Overview
The main histologic types of thyroid carcinoma include 1) differentiated, which includes papillary, follicular, and Hürthle cell carcinoma; 2) medullary carcinoma; and 3) anaplastic carcinoma (which is an aggressive undifferentiated tumor). An average of 58,629 patients per year were diagnosed with thyroid carcinoma between 2008 to 2012.1 Of these patients, 89% had papillary carcinoma, 5.1% had follicular carcinoma, 2.2% had Hürthle cell, 1.7% had medullary carcinoma, and 0.8% had anaplastic thyroid carcinoma (ATC).1 The 5-year relative survival rates for patients with papillary and follicular carcinomas (stages I–III) were 98% and 90%, respectively.2 In contrast, the 5-year relative survival rate for ATC is about 7%.2
This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Thyroid Carcinoma focuses on ATC, because substantial changes were made to the systemic therapy recommendations for the 2015 update (available online, in these guidelines, at NCCN.org [ANAP-A]). The complete version of the NCCN Guidelines for Thyroid Carcinoma addresses all aspects of management for the different types of thyroid carcinoma, including papillary, follicular, Hürthle cell, medullary, and anaplastic carcinoma. Additional sections are included in the complete version of these guidelines, such as Nodule Evaluation, Principles of Thyroid Stimulating Hormone (TSH) Suppression, Principles of Kinase Inhibitor Therapy in Advanced Thyroid Carcinoma, and the AJCC staging tables.2 The complete version of the NCCN Guidelines for Thyroid Carcinoma is updated at least once a year (to view the most recent version of these guidelines, visit the NCCN Web site at NCCN.org).
The summary of the guidelines updates briefly describes the new changes for the NCCN Guidelines for 2015 (see the complete version of the NCCN Guidelines for Thyroid Carcinoma at NCCN.org). A brief introduction to thyroid carcinoma is provided
NCCN Clinical Practice Guidelines in Oncology: Anaplastic Thyroid Carcinoma, Version 2.2015
Version 2.2015, 07-29-15 ©2015 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 13, 9; 10.6004/jnccn.2015.0139
Epidemiology
Thyroid nodules are approximately 4 times more common in women than in men. Palpable nodules increase in frequency throughout life, reaching a prevalence of about 5% in the United States population for individuals ages 50 years and older.3–5 Nodules are even more prevalent when the thyroid gland is examined at autopsy or surgery or when ultrasonography is used; 50% of the thyroids studied have nodules, which are almost always benign.4,6 New nodules develop at a rate of about 0.1% per year, beginning in early life, but nodules develop at a much higher rate (approximately 2% per year) after exposure to head and neck irradiation.7,8
By contrast, thyroid carcinoma is uncommon. For the United States population, the lifetime risk of being diagnosed with thyroid carcinoma is 1.1%.1 Experts estimate that approximately 62,450 new cases of thyroid carcinoma will be diagnosed in the United States in 2015.9 As with thyroid nodules, thyroid carcinoma occurs 2 to 3 times more often in women than in men. Thyroid carcinoma is currently the fourth most common malignancy diagnosed in women.9 Among persons aged 20 to 34 years, thyroid carcinoma accounts for 15.1% of all thyroid malignancies.1 The disease is also diagnosed more often in white North Americans than in African Americans. Although thyroid carcinoma can occur at any age, the peak incidence is age 50 years.1
Incidence and Mortality Rates
Experts estimated that approximately 1950 cancer deaths will occur in 2015 among persons with thyroid carcinoma in the United States.9–15 ATC is almost uniformly lethal; however, most thyroid carcinoma deaths are from papillary, follicular, and Hürthle cell carcinomas, because they account for nearly 95% of all thyroid carcinoma cases. Although thyroid carcinoma occurs more often in women, mortality rates are lower for younger women.10–14 The incidence of thyroid carcinoma increased almost 310% between 1950 and 2004, but mortality rates decreased more than 44%.13 From 1975 to 2004, thyroid cancer rates doubled in the United States.15 From 1975 to 2009, thyroid cancer rates tripled, mainly because of small papillary thyroid cancers.16 Although the estimated incidence of thyroid carcinoma increased between 2013 and 2014 (60,220 vs 62,980, respectively), the estimated incidence did not increase between 2014 and 2015 (62,980 vs 62,450, respectively).9,17 Because overall mortality has not dramatically increased since 1975 (1150 vs 1950 deaths), the increasing incidence may reflect, at least in part, earlier detection of subclinical disease (ie, small papillary cancers).15,16,18–20 However, recent data show the incidence has increased by varying degrees across all tumor sizes.21–25 The stable age- and gender-adjusted mortality rate for thyroid carcinoma contrasts distinctly with the declining rates for other solid tumors in adults.26,27
ATC
ATCs are aggressive undifferentiated tumors, with a disease-specific mortality approaching 100%.28 Patients with anaplastic carcinoma are often older than those with differentiated carcinomas, with a mean age at diagnosis of approximately 71 years.29 Fewer than 10% of patients are younger than age 50 years, and 60% to 70% of patients are women.29,30 The incidence of ATC is decreasing because of better management of differentiated thyroid cancer and because of increased iodine in the diet.28,31 As previously mentioned, anaplastic carcinoma is the least common type of thyroid carcinoma. An average of 58,629 patients per year were diagnosed with thyroid carcinoma between 2008 and 2012, but only 499 patients per year had ATC.1
Approximately 50% of patients with ATC have either a prior or coexisting differentiated carcinoma. Anaplastic carcinoma develops from more differentiated tumors as a result of one or more dedifferentiating steps, particularly loss of the p53 tumor suppressor protein.32 No precipitating events have been identified, and the mechanisms leading to anaplastic transformation of differentiated carcinomas are uncertain. Iodine deficiency is associated with ATC. More than 80% of patients with ATC have a history of goiter.31,33,34 Differentiated thyroid carcinomas can concentrate iodine, express TSH receptor, and produce thyroglobulin (Tg), whereas poorly differentiated or undifferentiated carcinomas typically do not. Therefore, 131I imaging and Tg measurement cannot be used in patients with ATC; radioactive iodine treatment is not effective.31
ATC is typically diagnosed based on clinical symptoms, unlike differentiated thyroid carcinoma, which is typically diagnosed after fine-needle aspiration (FNA) on a suspicious thyroid nodule. Patients with ATC may present with symptoms such as rapidly enlarging neck mass, dyspnea, dysphagia, neck pain, Horner's syndrome, stroke, and hoarseness due to vocal cord paralysis.35 Patients with ATC present with extensive local invasion, and distant metastases are found at initial disease presentation in 15% to 50% of patients.36,37 The lungs and pleura are the most common site of distant metastases (≤90% of patients with distant disease). About 5% to 15% of patients have bone metastases; 5% have brain metastases; and a few have metastases to the skin, liver, kidneys, pancreas, heart, and adrenal glands.
Diagnosis
Cytologic examination of an FNA specimen from a neck mass or nodule is categorized as 1) carcinoma (papillary, medullary, or anaplastic) or suspicious for carcinoma; 2) follicular or Hürthle cell neoplasm; 3) atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS); 4) thyroid lymphoma; 5) benign (ie, nodular goiter, colloid goiter, hyperplastic/adenomatoid nodule, Hashimoto's thyroiditis); or 6) insufficient biopsy (nondiagnostic) (see Nodule Evaluation in the complete version of these guidelines, available online at NCCN.org). These diagnostic categories for FNA results reflect the NCI's State of the Science Conference held in 2007.38,39
Pathology and cytopathology slides should be reviewed at the treating institution by a pathologist with expertise in the diagnosis of thyroid disorders. Although FNA is a very sensitive test—particularly for papillary thyroid carcinoma—false-negative results are sometimes obtained; therefore, a reassuring FNA should not override worrisome clinical findings.40,41
If FNA results are suspicious or not definitive, core or surgical biopsy should be performed to establish the diagnosis of ATC.31 Discriminating between ATC and other primary thyroid malignancies (ie, medullary thyroid carcinoma [MTC], thyroid lymphoma, sarcoma) or poorly differentiated cancers that metastasize to the thyroid, such as melanoma, is sometimes difficult.31,39,42 The appearance of ATCs varies widely; many have mixed morphologies. The most common morphology is biphasic spindle and giant cell tumor. Molecular techniques are not recommended for diagnosis of ATC.31 Additional immunohistochemical studies (eg, calcitonin) may occasionally be required to confirm the diagnosis of MTC.39 Hürthle cell neoplasms can sometimes mimic MTC cytologically and on frozen section. Metastatic renal carcinoma can mimic a follicular neoplasm, melanoma can mimic MTC, and metastatic lung cancer can mimic ATC.39 Pathology synoptic reports (protocols) are useful for reporting results from examinations of surgical specimens, such as those from the College of American Pathologists (CAP). The CAP protocol template may be useful; the protocol was updated in August 2014 and reflects the 2010 staging (7th edition) from the AJCC (see Protocol for the Examination of Specimens From Patients With Carcinomas of the Thyroid Gland on the CAP website).2,43
Diagnostic procedures include CBC, comprehensive chemistry, TSH level, and imaging studies. Neck ultrasound can rapidly assess tumor extension and invasion.35 CT scans of the neck can accurately determine the extent of the thyroid tumor and identify tumor invasion of the great vessels and upper aerodigestive tract structures.44 PET/CT scans are recommended to accurately stage the disease. Bone metastases are usually lytic. All ATCs are considered stage IV (A, B, or C) (see Table 1 in the complete version of the NCCN Guidelines for Thyroid Carcinoma, available at NCCN.org). The T4 category includes 1) T4a tumors that are intrathyroidal; and 2) T4b tumors that are extrathyroidal. Clinically apparent anaplastic tumors are usually unresectable.
Prognosis
No curative therapy exists for ATC; it is almost uniformly fatal.45,46 The median survival from diagnosis is about 5 months.31,47 The 1-year relative survival rate is about 18%.2 Death is attributable to upper airway obstruction and suffocation (often despite tracheostomy) in 50% of these patients; in the remaining patients, death is attributable to complications of local and distant disease or therapy.48 Patients with disease confined to the neck at diagnosis have a mean survival of 8 months compared with 3 months if the disease extends beyond the neck.49 Other variables that may predict a worse prognosis include older age at diagnosis, distant metastases, WBC of 10,000 mm3 or more, and dyspnea as a presenting symptom.50,51
Treatment
Surgery: After the diagnosis of ATC is confirmed, rapidly determining whether local resection is an option is essential.28 The surgeon should be experienced in accurately assessing the extent of disease and capable of performing extensive neck dissections if necessary. However, most patients with ATC have unresectable or metastatic disease. The patency of the airway should be assessed throughout the patient's course.48 If the patient appears to have resectable disease, an attempt at total thyroidectomy with complete gross tumor resection should be made, with selective resection of all involved local or regional structures and nodes. Total thyroidectomy with attempted complete tumor resection has not been shown to prolong survival except for the few patients whose tumors are small and confined entirely to the thyroid or readily excised structures.47,49,52,53 Patients need to receive levothyroxine if total thyroidectomy is performed.
The most common significant complications of thyroidectomy are hypoparathyroidism and recurrent laryngeal nerve injury, which occur more frequently after total thyroidectomy. Transient clinical hypoparathyroidism after surgery is common in adults undergoing total thyroidectomy.54 The rates of long-term recurrent laryngeal nerve injury and hypoparathyroidism, respectively, were 3% and 2.6% after total thyroidectomy and were 1.9% and 0.2% after subtotal thyroidectomy.55 One study reported hypocalcemia in 5.4% of patients immediately after total thyroidectomy, persisting in only 0.5% of patients 1 year later.56 Another study reported a 3.4% incidence of long-term recurrent laryngeal nerve injury and a 1.1% incidence of permanent hypocalcemia.57
When experienced surgeons perform thyroidectomies, complications occur at a lower rate. A study of 5860 patients found that surgeons who performed more than 100 thyroidectomies a year had the lowest overall complication rate (4.3%), whereas surgeons who performed fewer than 10 thyroidectomies a year had 4 times as many complications.58
ATC has a very poor prognosis and responds poorly to conventional therapy. The role of palliative and supportive care is paramount and should be initiated early in the disease. It is important that the surgeon be very experienced in evaluating the extent of disease—particularly in the larynx, trachea, and neck—before attempting resection. At the outset of the diagnosis, it is critical that conversations about end-of-life care be initiated so that a clear understanding of how to manage the airway is undertaken, which is clear to the family and all providers. Tracheostomy is often a morbid and temporary treatment of the airway and may not be the option a patient would choose.
Radiation Therapy: External-beam radiation therapy (EBRT)/intensity-modulated radiation therapy (IMRT) can increase short-term survival in some patients; EBRT can also improve local control and can also be used for palliation (eg, to prevent asphyxiation).28,31,51,59–62 Surgical excision or external irradiation should be considered for isolated skeletal metastases. For solitary brain lesions, neurosurgical resection, radiation therapy, or both are recommended.31,63 After brain metastases are diagnosed, disease-specific mortality is very high, with a reported median survival of 1.3 months.63 Enteral nutrition may be useful for some patients who have difficulty swallowing (see Principles of Nutrition: Management and Supportive Care in the NCCN Guidelines for Head and Neck Cancer, available at NCCN.org).31 If enteral feeding is considered, a careful conversation should occur with the patient about their wishes.
Systemic Therapy: Treatment with single-drug chemotherapy is not very effective, although some patients may respond or have stable disease.31 Hyperfractionated EBRT, combined with radiosensitizing doses of doxorubicin, may increase the local response rate to about 80%, with subsequent median survival of 1 year.64 Distant metastases then become the leading cause of death.65 Similar improvement in local disease control has been reported with a combination of hyperfractionated RT and doxorubicin-based regimens, followed by surgery in patients who respond or other multimodality approaches.66–68 IMRT may be useful to reduce toxicity.31,60,69–73 However, the addition of larger doses of other chemotherapeutic drugs has not been associated with improved control of distant disease or with improved survival.
Systemic therapy recommendations are described in the algorithm (see ANAP-A; page 1143).31,74 For the 2015 update, the recommended systemic therapy regimens for ATC were revised based on the guidelines from the American Thyroid Association (ATA) guidelines.31 Docetaxel/doxorubicin regimens were added, which can be used with or without radiation therapy.31,75,76 Single-agent cisplatin was deleted, because it is not recommended for patients with advanced/metastatic ATC or those with impaired renal function. In addition, the dosage and frequency of administration of all the recommended systemic therapy agents are now provided. Either concurrent chemoradiation or chemotherapy alone regimens may be used depending on the clinical setting; however, chemoradiation is generally more toxic. If using chemoradiation, the ATA guidelines recommend using weekly chemotherapy regimens.31
Chemotherapy alone can be considered for patients with unresectable or metastatic disease. Single-agent doxorubicin is the only agent that is approved by the FDA for ATC.31 Single-agent paclitaxel may benefit some newly diagnosed patients; increased survival has been reported in patients with stage IVB disease.77–79 If weekly paclitaxel is used, the ATA guidelines recommend using paclitaxel at 60 to 90 mg/m2 intravenously weekly and not the dose previously reported.31,79 Note that carboplatin is dosed using the following: 1) Calvert formula with the Cockroft & Gault equation; 2) actual body weight; and 3) a minimum serum creatinine value of 0.7 mg/dL (http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ucm228974.htm).
Given the poor outcome with current standard therapy, all patients—regardless of surgical resection—should be considered for clinical trials. Clinical trials include fosbretabulin (and its parent drug, combretastatin A4 phosphate [CA4P], and crolibulin [EPC2407], which are vascular disrupting agents), efatutazone (an oral PPAR gamma agonist), and novel multitargeted therapies including bevacizumab with doxorubicin, sorafenib, sunitinib, imatinib, and pazopanib.74,80–89 Outside of clinical trials, targeted therapies are not currently recommended for patients with ATC in the NCCN Guidelines, although some are recommended for patients with papillary, follicular, Hürthle cell, or medullary carcinoma.
A trial in 80 patients (FACT) reported that the addition of fosbretabulin—to a carboplatin/paclitaxel regimen—resulted in a nonsignificant increase in median survival (5.2 vs 4.0 months).74,90 Multimodality therapy is recommended in patients with locally resectable disease (see ANAP-1; page 1142).31,69,74,91–95 Although optimal results have been reported with hyperfractionated EBRT combined with chemotherapy, the NCCN panel acknowledged that considerable toxicity is associated with such treatment and that prolonged remission is uncommon.96 Preliminary data suggest that anaplastic lymphoma kinase (ALK) inhibitors may be effective in a subset of patients with papillary thyroid cancer who have ALK gene fusions; however, these ALK gene fusions are rarely reported in patients with ATC.97–100 BRAF mutations have been reported in patients with ATC.35,101–103
Individual Disclosures of the NCCN Anaplastic Thyroid Carcinoma Panel
References
- 1.↑
Howlader N, Noone A, Krapcho M et al.. SEER Cancer Statistics Review, 1975-2012, based on November 2014 SEER data submission, posted to the SEER web site, April 2015. Bethesda, MD: National Cancer Institute; 2015. Available at: http://seer.cancer.gov/csr/1975_2012/.
- 2.↑
Edge SB, Byrd DR, Compton CC et al.. AJCC Cancer Staging Manual, 7th ed. New York: Springer; 2010:1–646.
- 3.↑
Mazzaferri EL. Thyroid carcinoma: papillary and follicular. In: Mazzaferri EL, Samaan N, eds. Endocrine Tumors. Cambridge: Blackwell Scientific Publications 1993:278–333.
- 5.↑
Cooper DS, Doherty GM, Haugen BR et al.. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009;19:1167–1214.
- 6.↑
Ezzat S, Sarti DA, Cain DR, Braunstein GD. Thyroid incidentalomas: prevalence by palpation and ultrasonography. Arch Intern Med 1994;154:1838–1840.
- 7.↑
Ron E, Lubin JH, Shore RE et al.. Thyroid cancer after exposure to external radiation: a pooled analysis of seven studies. Radiat Res 1995;141:259–277.
- 8.↑
Schneider AB, Bekerman C, Leland J et al.. Thyroid nodules in the follow-up of irradiated individuals: comparison of thyroid ultrasound with scanning and palpation. J Clin Endocrinol Metab 1997;82:4020–4027.
- 10.↑
Jonklaas J, Nogueras-Gonzalez G, Munsell M et al.. The impact of age and gender on papillary thyroid cancer survival. J Clin Endocrinol Metab 2012;97:E878–887.
- 11.
Stroup AM, Harrell CJ, Herget KA. Long-term survival in young women: hazards and competing risks after thyroid cancer. J Cancer Epidemiol 2012;2012:641372.
- 12.
Altekruse S, Kosary C, Krapcho M et al.. SEER Cancer Statistics Review, 1975–2007. Bethesda, MD: National Cancer Institute; 2010.
- 14.↑
Mazzaferri EL, Jhiang SM. Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med 1994;97:418–428.
- 15.↑
Davies L, Welch HG. Increasing incidence of thyroid cancer in the United States, 1973–2002. JAMA 2006;295:2164–2167.
- 16.↑
Davies L, Welch HG. Current thyroid cancer trends in the United States. JAMA Otolaryngol Head Neck Surg 2014;140:317–322.
- 18.↑
Li N, Du XL, Reitzel LR et al.. Impact of enhanced detection on the increase in thyroid cancer incidence in the United States: review of incidence trends by socioeconomic status within the surveillance, epidemiology, and end results registry, 1980-2008. Thyroid 2013;23:103–110.
- 19.
Wilhelm S. Evaluation of thyroid incidentaloma. Surg Clin North Am 2014;94:485–497.
- 20.↑
Ito Y, Tomoda C, Uruno T et al.. Papillary microcarcinoma of the thyroid: how should it be treated? World J Surg 2004;28:1115–1121.
- 21.↑
Aschebrook-Kilfoy B, Grogan RH, Ward MH et al.. Follicular thyroid cancer incidence patterns in the United States, 1980–2009. Thyroid 2013;23:1015–1021.
- 22.
Aschebrook-Kilfoy B, Ward MH, Sabra MM, Devesa SS. Thyroid cancer incidence patterns in the United States by histologic type, 1992–2006. Thyroid 2011;21:125–134.
- 23.
Yu GP, Li JC, Branovan D et al.. Thyroid cancer incidence and survival in the national cancer institute surveillance, epidemiology, and end results race/ethnicity groups. Thyroid 2010;20:465–473.
- 24.
Chen AY, Jemal A, Ward EM. Increasing incidence of differentiated thyroid cancer in the United States, 1988–2005. Cancer 2009;115:3801–3807.
- 25.↑
Enewold L, Zhu K, Ron E et al.. Rising thyroid cancer incidence in the United States by demographic and tumor characteristics, 1980–2005. Cancer Epidemiol Biomarkers Prev 2009;18:784–791.
- 26.↑
Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin 2011;61:212–236.
- 28.↑
Are C, Shaha AR. Anaplastic thyroid carcinoma: biology, pathogenesis, prognostic factors, and treatment approaches. Ann Surg Oncol 2006;13:453–464.
- 29.↑
Kebebew E, Greenspan FS, Clark OH et al.. Anaplastic thyroid carcinoma: treatment outcome and prognostic factors. Cancer 2005;103:1330–1335.
- 30.↑
Gilliland FD, Hunt WC, Morris DM, Key CR. Prognostic factors for thyroid carcinoma: a population-based study of 15,698 cases from the Surveillance, Epidemiology and End Results (SEER) program 1973–1991. Cancer 1997;79:564–573.
- 31.↑
Smallridge RC, Ain KB, Asa SL et al.. American Thyroid Association guidelines for management of patients with anaplastic thyroid cancer. Thyroid 2012;22:1104–1139.
- 32.↑
Moretti F, Farsetti A, Soddu S et al.. p53 re-expression inhibits proliferation and restores differentiation of human thyroid anaplastic carcinoma cells. Oncogene 1997;14:729–740.
- 33.↑
Maatouk J, Barklow TA, Zakaria W, Al-Abbadi MA. Anaplastic thyroid carcinoma arising in long-standing multinodular goiter following radioactive iodine therapy: report of a case diagnosed by fine needle aspiration. Acta Cytol 2009;53:581–583.
- 34.↑
Aldinger KA, Samaan NA, Ibanez M & Hill CS Jr. Anaplastic carcinoma of the thyroid: a review of 84 cases of spindle and giant cell carcinoma of the thyroid. Cancer 1978;41:2267–2275.
- 35.↑
Keutgen XM, Sadowski SM, Kebebew E. Management of anaplastic thyroid cancer. Gland Surg 2015;4:44–51.
- 36.↑
Thompson LD, Wieneke JA, Paal E et al.. A clinicopathologic study of minimally invasive follicular carcinoma of the thyroid gland with a review of the English literature. Cancer 2001;91:505–524.
- 37.↑
Sherman SI. Anaplastic carcinoma: Clinical aspects. In: Wartofsky L, Van Nostrand D, eds. Thyroid Cancer: A Comprehensive Guide to Clinical Management, 2nd ed. Totowa, NJ: Humana Press; 2006:629–632.
- 38.↑
Layfield LJ, Cibas ES, Gharib H, Mandel SJ. Thyroid aspiration cytology: current status. CA Cancer J Clin 2009;59:99–110.
- 39.↑
Baloch ZW, Cibas ES, Clark DP et al.. The National Cancer Institute Thyroid Fine Needle Aspiration State of the Science Conference: a summation. Cytojournal 2008;5:6.
- 40.↑
Eilers SG, LaPolice P, Mukunyadzi P et al.. Thyroid fine-needle aspiration cytology: performance data of neoplastic and malignant cases as identified from 1558 responses in the ASCP Non-GYN Assessment program thyroid fine-needle performance data. Cancer Cytopathol 2014;122:745–750.
- 41.↑
Yeh MW, Demircan O, Ituarte P, Clark OH. False-negative fine-needle aspiration cytology results delay treatment and adversely affect outcome in patients with thyroid carcinoma. Thyroid 2004;14:207–215.
- 42.↑
Asa SL, Bedard YC. Fine-needle aspiration cytology and histopathology. In: Clark OH, Noguchi S, eds. Thyroid Cancer: Diagnosis and Treatment. St Louis: Quality Medical Publishing; 2000:105–126.
- 43.↑
Seethala RR, Asa SL, Carty SE et al.. Protocol for the examination of specimens from patients with carcinomas of the thyroid gland: based on AJCC/UICC TNM, 7th edition: Protocol web posting date: August 2014: College of American Pathologists; 2014. Available at: http://www.cap.org/web/home/resources/cancer-reporting-tools/cancer-protocol-templates.
- 44.↑
Takashima S, Morimoto S, Ikezoe J et al.. CT evaluation of anaplastic thyroid carcinoma. AJR Am J Roentgenol 1990;154:1079–1085.
- 45.↑
Neff RL, Farrar WB, Kloos RT, Burman KD. Anaplastic thyroid cancer. Endocrinol Metab Clin North Am 2008;37:525–538, xi.
- 46.↑
Wein RO, Weber RS. Anaplastic thyroid carcinoma: palliation or treatment? Curr Opin Otolaryngol Head Neck Surg 2011;19:113–118.
- 47.↑
Untch BR & Olson JA Jr. Anaplastic thyroid carcinoma, thyroid lymphoma, and metastasis to thyroid. Surg Oncol Clin N Am 2006;15:661–679, x.
- 49.↑
Venkatesh YS, Ordonez NG, Schultz PN et al.. Anaplastic carcinoma of the thyroid: a clinicopathologic study of 121 cases. Cancer 1990;66:321–330.
- 50.↑
Sugitani I, Miyauchi A, Sugino K et al.. Prognostic factors and treatment outcomes for anaplastic thyroid carcinoma: ATC Research Consortium of Japan cohort study of 677 patients. World J Surg 2012;36:1247–1254.
- 51.↑
Akaishi J, Sugino K, Kitagawa W et al.. Prognostic factors and treatment outcomes of 100 cases of anaplastic thyroid carcinoma. Thyroid 2011;21:1183–1189.
- 52.↑
Junor EJ, Paul J, Reed NS. Anaplastic thyroid carcinoma: 91 patients treated by surgery and radiotherapy. Eur J Surg Oncol 1992;18:83–88.
- 53.↑
McIver B, Hay ID, Giuffrida DF et al.. Anaplastic thyroid carcinoma: a 50-year experience at a single institution. Surgery 2001;130:1028–1034.
- 54.↑
Burge MR, Zeise TM, Johnsen MW et al.. Risks of complication following thyroidectomy. J Gen Intern Med 1998;13:24–31.
- 55.↑
Udelsman R, Lakatos E, Ladenson P. Optimal surgery for papillary thyroid carcinoma. World J Surg 1996;20:88–93.
- 56.↑
Pattou F, Combemale F, Fabre S et al.. Hypocalcemia following thyroid surgery: incidence and prediction of outcome. World J Surg 1998;22:718–724.
- 57.↑
Hassanain M, Wexler M. Conservative management of well-differentiated thyroid cancer. Can J Surg 2010;53:109–118.
- 58.↑
Sosa JA, Bowman HM, Tielsch JM et al.. The importance of surgeon experience for clinical and economic outcomes from thyroidectomy. Ann Surg 1998;228:320–330.
- 59.↑
Dumke AK, Pelz T, Vordermark D. Long-term results of radiotherapy in anaplastic thyroid cancer. Radiat Oncol 2014;9:90.
- 60.↑
Brierley J, Sherman E. The role of external beam radiation and targeted therapy in thyroid cancer. Semin Radiat Oncol 2012;22:254–262.
- 61.
Burnison CM, Lim S. Multimodal approach to anaplastic thyroid cancer. Oncology (Williston Park) 2012;26:378–384, 390.
- 62.↑
Wang Y, Tsang R, Asa S et al.. Clinical outcome of anaplastic thyroid carcinoma treated with radiotherapy of once- and twice-daily fractionation regimens. Cancer 2006;107:1786–1792.
- 63.↑
Chiu AC, Delpassand ES, Sherman SI. Prognosis and treatment of brain metastases in thyroid carcinoma. J Clin Endocrinol Metab 1997;82:3637–3642.
- 64.↑
De Crevoisier R, Baudin E, Bachelot A et al.. Combined treatment of anaplastic thyroid carcinoma with surgery, chemotherapy, and hyperfractionated accelerated external radiotherapy. Int J Radiat Oncol Biol Phys 2004;60:1137–1143.
- 65.↑
Kim JH, Leeper RD. Treatment of locally advanced thyroid carcinoma with combination doxorubicin and radiation therapy. Cancer 1987;60:2372–2375.
- 66.↑
Mohebati A, Dilorenzo M, Palmer F et al.. Anaplastic thyroid carcinoma: a 25-year single-institution experience. Ann Surg Oncol 2014;21:1665–1670.
- 67.
Derbel O, Limem S, Segura-Ferlay C et al.. Results of combined treatment of anaplastic thyroid carcinoma (ATC). BMC Cancer 2011;11:469.
- 68.↑
Wallin G, Lundell G, Tennvall J. Anaplastic giant cell thyroid carcinoma. Scand J Surg 2004;93:272–277.
- 69.↑
Smallridge RC. Approach to the patient with anaplastic thyroid carcinoma. J Clin Endocrinol Metab 2012;97:2566–2572.
- 70.
Bhatia A, Rao A, Ang KK et al.. Anaplastic thyroid cancer: Clinical outcomes with conformal radiotherapy. Head Neck 2010;32:829–836.
- 71.
Sun XS, Sun SR, Guevara N et al.. Chemoradiation in anaplastic thyroid carcinomas. Crit Rev Oncol Hematol 2013;86:290–301.
- 72.
Gregoire V, Mackie TR. State of the art on dose prescription, reporting and recording in Intensity-Modulated Radiation Therapy (ICRU report No. 83). Cancer Radiother 2011;15:555–559.
- 73.↑
Prescribing, Recording, and Reporting Photon-Beam Intensity-Modulated Radiation Therapy (IMRT): Contents. J ICRU 2010;10:NP.
- 74.↑
Sosa JA, Balkissoon J, Lu SP et al.. Thyroidectomy followed by fosbretabulin (CA4P) combination regimen appears to suggest improvement in patient survival in anaplastic thyroid cancer. Surgery 2012;152:1078–1087.
- 75.↑
Swaak-Kragten AT, de Wilt JH, Schmitz PI et al.. Multimodality treatment for anaplastic thyroid carcinoma--treatment outcome in 75 patients. Radiother Oncol 2009;92:100–104.
- 76.↑
Lowe NM, Loughran S, Slevin NJ, Yap BK. Anaplastic thyroid cancer: the addition of systemic chemotherapy to radiotherapy led to an observed improvement in survival: a single centre experience and review of the literature. Scientific World J 2014;2014:674583.
- 77.↑
Higashiyama T, Ito Y, Hirokawa M et al.. Induction chemotherapy with weekly paclitaxel administration for anaplastic thyroid carcinoma. Thyroid 2010;20:7–14.
- 78.
Ain KB. Anaplastic thyroid carcinoma: behavior, biology, and therapeutic approaches. Thyroid 1998;8:715–726.
- 79.↑
Ain KB, Egorin MJ, DeSimone PA. Treatment of anaplastic thyroid carcinoma with paclitaxel: phase 2 trial using ninety-six-hour infusion. Collaborative Anaplastic Thyroid Cancer Health Intervention Trials (CATCHIT) Group. Thyroid 2000;10:587–594.
- 80.↑
Bible KC, Suman VJ, Menefee ME et al.. A multiinstitutional phase 2 trial of pazopanib monotherapy in advanced anaplastic thyroid cancer. J Clin Endocrinol Metab 2012;97:3179–3184.
- 81.
Ha HT, Lee JS, Urba S et al.. A phase II study of imatinib in patients with advanced anaplastic thyroid cancer. Thyroid 2010;20:975–980.
- 82.
Savvides P, Nagaiah G, Lavertu P et al.. Phase II trial of sorafenib in patients with advanced anaplastic carcinoma of the thyroid. Thyroid 2013;23:600–604.
- 83.
Keefe SM, Troxel AB, Rhee S et al.. Phase II trial of sorafenib in patients with advanced thyroid cancer [abstract]. J Clin Oncol 2011;29(Suppl 15):Abstract 5562.
- 84.
Brose MS, Nutting CM, Sherman SI et al.. Rationale and design of decision: a double-blind, randomized, placebo-controlled phase III trial evaluating the efficacy and safety of sorafenib in patients with locally advanced or metastatic radioactive iodine (RAI)-refractory, differentiated thyroid cancer. BMC Cancer 2011;11:349.
- 85.
Antonelli A, Fallahi P, Ulisse S et al.. New targeted therapies for anaplastic thyroid cancer. Anticancer Agents Med Chem 2012;12:87–93.
- 86.
Perri F, Lorenzo GD, Scarpati GD, Buonerba C. Anaplastic thyroid carcinoma: a comprehensive review of current and future therapeutic options. World J Clin Oncol 2011;2:150–157.
- 87.
Deshpande HA, Gettinger SN, Sosa JA. Novel chemotherapy options for advanced thyroid tumors: small molecules offer great hope. Curr Opin Oncol 2008;20:19–24.
- 88.
Mooney CJ, Nagaiah G, Fu P et al.. A phase II trial of fosbretabulin in advanced anaplastic thyroid carcinoma and correlation of baseline serum-soluble intracellular adhesion molecule-1 with outcome. Thyroid 2009;19:233–240.
- 89.↑
Smallridge RC, Marlow LA, Copland JA. Anaplastic thyroid cancer: molecular pathogenesis and emerging therapies. Endocr Relat Cancer 2009;16:17–44.
- 90.↑
Sosa JA, Elisei R, Jarzab B et al.. Randomized safety and efficacy study of fosbretabulin with paclitaxel/carboplatin against anaplastic thyroid carcinoma. Thyroid 2014;24:232–240.
- 91.↑
Foote RL, Molina JR, Kasperbauer JL et al.. Enhanced survival in locoregionally confined anaplastic thyroid carcinoma: a single-institution experience using aggressive multimodal therapy. Thyroid 2011;21:25–30.
- 92.
Nagaiah G, Hossain A, Mooney CJ et al.. Anaplastic thyroid cancer: a review of epidemiology, pathogenesis, and treatment. J Oncol 2011;2011:542358.
- 93.
Siironen P, Hagstrom J, Maenpaa HO et al.. Anaplastic and poorly differentiated thyroid carcinoma: therapeutic strategies and treatment outcome of 52 consecutive patients. Oncology 2010;79:400–408.
- 94.
Brignardello E, Gallo M, Baldi I et al.. Anaplastic thyroid carcinoma: clinical outcome of 30 consecutive patients referred to a single institution in the past 5 years. Eur J Endocrinol 2007;156:425–430.
- 95.↑
Yau T, Lo CY, Epstein RJ et al.. Treatment outcomes in anaplastic thyroid carcinoma: survival improvement in young patients with localized disease treated by combination of surgery and radiotherapy. Ann Surg Oncol 2008;15:2500–2505.
- 96.↑
Heron DE, Karimpour S, Grigsby PW. Anaplastic thyroid carcinoma: comparison of conventional radiotherapy and hyperfractionation chemoradiotherapy in two groups. Am J Clin Oncol 2002;25:442–446.
- 97.↑
Chou A, Fraser S, Toon CW et al.. A detailed clinicopathologic study of ALK-translocated papillary thyroid carcinoma. Am J Surg Pathol 2015;39:652–659.
- 98.
Park G, Kim TH, Lee HO et al.. Standard immunohistochemistry efficiently screens for anaplastic lymphoma kinase rearrangements in differentiated thyroid cancer. Endocr Relat Cancer 2015;22:55–63.
- 99.
Perot G, Soubeyran I, Ribeiro A et al.. Identification of a recurrent STRN/ALK fusion in thyroid carcinomas. PLoS One 2014;9:e87170.
- 100.↑
Kelly LM, Barila G, Liu P et al.. Identification of the transforming STRN-ALK fusion as a potential therapeutic target in the aggressive forms of thyroid cancer. Proc Natl Acad Sci U S A 2014;111:4233–4238.
- 101.↑
Kunstman JW, Juhlin CC, Goh G et al.. Characterization of the mutational landscape of anaplastic thyroid cancer via whole-exome sequencing. Hum Mol Genet 2015;24:2318–2329.
- 102.
Rosove MH, Peddi PF, Glaspy JA. BRAF V600E inhibition in anaplastic thyroid cancer. N Engl J Med 2013;368:684–685.
- 103.↑
Takano T, Ito Y, Hirokawa M et al.. BRAF V600E mutation in anaplastic thyroid carcinomas and their accompanying differentiated carcinomas. Br J Cancer 2007;96:1549–1553.
