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Incidence and Mortality
Estimated new cases and deaths from thyroid cancer in the United States in 2015:
Carcinoma of the thyroid gland is an uncommon cancer but is the most common malignancy of the endocrine system. Differentiated tumors (papillary or follicular) are highly treatable and usually curable. Poorly differentiated tumors (medullary or anaplastic) are much less common, are aggressive, metastasize early, and have a much poorer prognosis. Thyroid cancer affects women more often than men and usually occurs in people between the ages of 25 and 65 years. The incidence of this malignancy has been increasing over the last decade. Thyroid cancer commonly presents as a cold nodule. The overall incidence of cancer in a cold nodule is 12% to 15%, but it is higher in people younger than 40 years and in people with calcifications present on preoperative ultrasonography.[3,4]
Patients with a history of radiation administered in infancy and childhood for benign conditions of the head and neck, such as enlarged thymus, acne, or tonsillar or adenoidal enlargement, have an increased risk of cancer as well as other abnormalities of the thyroid gland. In this group of patients, malignancies of the thyroid gland first appear beginning as early as 5 years following radiation and may appear 20 or more years later. Radiation exposure as a consequence of nuclear fallout has also been associated with a high risk of thyroid cancer, especially in children.[6,7,8] Other risk factors for the development of thyroid cancer include the following:
The prognosis for differentiated carcinoma is better for patients younger than 40 years without extracapsular extension or vascular invasion.[10,11,12,13,14] Age appears to be the single most important prognostic factor. The prognostic significance of lymph node status is controversial. One retrospective surgical series of 931 previously untreated patients with differentiated thyroid cancer found that female gender, multifocality, and regional node involvement are favorable prognostic factors. Adverse factors included age older than 45 years, follicular histology, primary tumor larger than 4 cm (T2–T3), extrathyroid extension (T4), and distant metastases.[15,16] Other studies, however, have shown that regional lymph node involvement had no effect [17,18] or even an adverse effect on survival.[13,14,19] Use of sentinel lymph node biopsy may aid in identifying patients with occult metastases who might benefit from central neck dissection.
Risk factors and survivorship
Diffuse, intense immunostaining for vascular endothelial growth factor in patients with papillary cancer has been associated with a high rate of local recurrence and distant metastases. An elevated serum thyroglobulin level correlates strongly with recurrent tumor when found in patients with differentiated thyroid cancer during postoperative evaluations.[22,23] Serum thyroglobulin levels are most sensitive when patients are hypothyroid and have elevated serum thyroid-stimulating hormone levels. Expression of the tumor suppressor gene p53 has also been associated with an adverse prognosis for patients with thyroid cancer.
Patients considered at low risk by the age, metastases, extent, and size (AMES) risk criteria include women younger than 50 years and men younger than 40 years without evidence of distant metastases. Also included in the low-risk group are older patients with primary tumors smaller than 5 cm and papillary cancer without evidence of gross extrathyroid invasion or follicular cancer without either major capsular invasion or blood vessel invasion. Using these criteria, a retrospective study of 1,019 patients showed that the 20-year survival rate is 98% for low-risk patients and 50% for high-risk patients. The 10-year overall relative survival rates for patients in the United States are 93% for papillary cancer, 85% for follicular cancer, 75% for medullary cancer, and 14% for undifferentiated/anaplastic cancer.
The thyroid gland may occasionally be the site of other primary tumors, including sarcomas, lymphomas, epidermoid carcinomas, and teratomas and may be the site of metastasis from other cancers, particularly of the lung, breast, and kidney.
Other PDQ summaries containing information related to thyroid cancer include the following:
Cell type is an important determinant of prognosis in thyroid cancer. There are four main varieties of thyroid cancer (although, for clinical management of the patient, thyroid cancer is generally divided into two categories: well differentiated or poorly differentiated):
A definition for each major type can be found under stage information.
Definitions of TNM
The American Joint Committee on Cancer (AJCC) has designated staging by TNM classification to define thyroid cancer.
Papillary and Follicular Thyroid Cancer
Stage I papillary thyroid cancer
Stage I papillary carcinoma is localized to the thyroid gland. In as many as 50% of cases, there are multifocal sites of papillary adenocarcinomas throughout the gland. Most papillary cancers have some follicular elements, and these may sometimes be more numerous than the papillary formations, but this does not change the prognosis. The 10-year survival rate is slightly better for patients younger than 45 years than for patients older than 45 years.
Stage II papillary thyroid cancer
Stage II papillary carcinoma is defined as either: (1) tumor that has spread distantly in patients younger than 45 years, or (2) tumor that is larger than 2 cm but 4 cm or smaller and is limited to the thyroid gland in patients older than 45 years. In as many as 50% to 80% of cases, there are multifocal sites of papillary adenocarcinomas throughout the gland. Most papillary cancers have some follicular elements, and these may sometimes be more numerous than the papillary formations, but this does not appear to change the prognosis.
Stage III papillary thyroid cancer
Stage III is papillary carcinoma in patients older than 45 years that is larger than 4 cm and is limited to the thyroid or with minimal extrathyroid extension, or positive lymph nodes limited to the pretracheal, paratracheal, or prelaryngeal/Delphian nodes. Papillary carcinoma that has invaded adjacent cervical tissue has a worse prognosis than tumors confined to the thyroid.
Stage IV papillary thyroid cancer
Stage IV is papillary carcinoma in patients older than 45 years with extension beyond the thyroid capsule to the soft tissues of the neck, cervical lymph node metastases, or distant metastases. The lungs and bone are the most frequent distant sites of spread, though such distant spread is rare in this type of thyroid cancer. Papillary carcinoma more frequently metastasizes to regional lymph nodes than to distant sites. The prognosis for patients with distant metastases is poor.
Stage I follicular thyroid cancer
Stage I follicular carcinoma is localized to the thyroid gland. Follicular thyroid carcinoma must be distinguished from follicular adenomas, which are characterized by their lack of invasion through the capsule into the surrounding thyroid tissue. While follicular cancer has a good prognosis, it is less favorable than that of papillary carcinoma. The 10-year survival is better for patients with follicular carcinoma without vascular invasion than it is for patients with vascular invasion.
Stage II follicular thyroid cancer
Stage II follicular carcinoma is defined as either tumor that has spread distantly in patients younger than 45 years, or tumor that is larger than 2 cm but 4 cm or smaller and is limited to the thyroid gland in patients older than 45 years. The presence of lymph node metastases does not worsen the prognosis among patients younger than 45 years. Follicular thyroid carcinoma must be distinguished from follicular adenomas, which are characterized by their lack of invasion through the capsule into the surrounding thyroid tissue. While follicular cancer has a good prognosis, it is less favorable than that of papillary carcinoma; the 10-year survival is better for patients with follicular carcinoma without vascular invasion than for patients with vascular invasion.
Stage III follicular thyroid cancer
Stage III is follicular carcinoma in patients older than 45 years, larger than 4 cm and limited to the thyroid or with minimal extrathyroid extension, or positive lymph nodes limited to the pretracheal, paratracheal, or prelaryngeal/Delphian nodes. Follicular carcinoma invading cervical tissue has a worse prognosis than tumors confined to the thyroid gland. The presence of vascular invasion is an additional poor prognostic factor. Metastases to lymph nodes do not worsen the prognosis in patients younger than 45 years.
Stage IV follicular thyroid cancer
Stage IV is follicular carcinoma in patients older than 45 years with extension beyond the thyroid capsule to the soft tissues of the neck, cervical lymph node metastases, or distant metastases. The lungs and bone are the most frequent sites of spread. Follicular carcinomas more commonly have blood vessel invasion and tend to metastasize hematogenously to the lungs and to the bone rather than through the lymphatic system. The prognosis for patients with distant metastases is poor.
Hürthle cell carcinoma
Hürthle cell carcinoma is a variant of follicular carcinoma with a similar prognosis and should be treated in the same way as equivalent stage non-Hürthle cell follicular carcinoma.
Medullary Thyroid Cancer
Several staging systems have been employed to correlate extent of disease with long-term survival in medullary thyroid cancer. The clinical staging system of the AJCC correlates survival to size of the primary tumor, presence or absence of lymph node metastases, and presence or absence of distance metastasis. Patients with the best prognosis are those who are diagnosed by provocative screening, prior to the appearance of palpable disease.
Stage 0 medullary thyroid cancer
Clinically occult disease detected by provocative biochemical screening.
Stage I medullary thyroid cancer
Tumor smaller than 2 cm.
Stage II medullary thyroid cancer
Tumor larger than 2 cm but 4 cm or smaller with no metastases or larger than 4 cm with minimal extrathyroid extension.
Stage III medullary thyroid cancer
Tumor of any size with metastases limited to the pretracheal, paratracheal, or prelaryngeal/Delphian lymph nodes.
Stage IV medullary thyroid cancer
Stage IV medullary thyroid cancer is divided into the following categories:
Medullary carcinoma usually presents as a hard mass and is often accompanied by blood vessel invasion. Medullary thyroid cancer occurs in two forms, sporadic and familial. In the sporadic form, the tumor is usually unilateral. In the familial form, the tumor is almost always bilateral. In addition, the familial form may be associated with benign or malignant tumors of other endocrine organs, commonly referred to as the multiple endocrine neoplasia syndromes (MEN 2A or MEN 2B).
In these syndromes, there is an association with pheochromocytoma of the adrenal gland and parathyroid hyperplasia. Medullary carcinoma usually secretes calcitonin, a hormonal marker for the tumor, and may be detectable in blood even when the tumor is clinically occult. Metastases to regional lymph nodes are found in about 50% of cases. Prognosis depends on extent of disease at presentation, presence or absence of regional lymph node metastases, and completeness of the surgical resection.
Family members should be screened for calcitonin elevation to identify individuals who are at risk of developing familial medullary thyroid cancer. MEN 2A gene carrier status can be more accurately determined by analysis of mutations in the RET gene. Whereas modest el mutation is the optimal approach in evaluating MEN 2A. All patients with medullary carcinoma of the thyroid (whether familial or sporadic) should be tested for RET mutations, and, if they are positive, family members should also be tested. Family members who are gene carriers should undergo prophylactic thyroidectomy at an early age.[5,6,7]
Anaplastic Thyroid Cancer
No generally accepted staging system is available for anaplastic thyroid cancer. All patients are considered to have stage IV disease.
Undifferentiated (anaplastic) carcinomas are highly malignant cancers of the thyroid. They may be subclassified as small cell or large cell carcinomas. Both grow rapidly and extend to structures beyond the thyroid. Both small cell and large cell carcinomas present as hard, ill-defined masses, often with extension into the structures surrounding the thyroid. Small cell anaplastic thyroid carcinoma must be carefully distinguished from lymphoma. This tumor usually occurs in an older age group and is characterized by extensive local invasion and rapid progression. Five-year survival with this tumor is poor. Death is usually from uncontrolled local cancer in the neck, usually within months of diagnosis.
Surgery is the therapy of choice for all primary lesions. Surgical options include total thyroidectomy or lobectomy. The choice of procedure is influenced mainly by the age of the patient and the size of the nodule. Survival results may be similar; the difference between them lies in the rates of surgical complications and local recurrences.[1,2,3,4,5,6,7]
Standard treatment options:
This procedure is advocated because of the high incidence of multicentric involvement of both lobes of the gland and the possibility of dedifferentiation of any residual tumor to the anaplastic cell type.
From the National Cancer Center Data Base (NCDB) registry of 52,173 patients, 43,227 (82.9%) underwent total thyroidectomy, and 8,946 (17.1%) underwent lobectomy. For a papillary thyroid cancer measuring less than 1 cm, the extent of surgery did not impact recurrence or survival (P = .24 and P = .83, respectively). For tumors measuring 1 cm or larger, lobectomy resulted in higher risk of recurrence and death (P = .04 and P = .009, respectively). To minimize the influence of larger tumors, 1-cm to 2-cm lesions were examined separately; lobectomy again resulted in a higher risk of recurrence and death (P = .04 and P = .04, respectively). In this study, total thyroidectomy resulted in lower recurrence rates and improved survival for patients with papillary thyroid cancer measuring 1 cm or larger compared with lobectomy.[Level of evidence: 3iiA]
Furthermore, in a pattern of care study, using the NCDB registry from 1985 to 2003, 57,243 papillary thyroid cancer patients with tumors measuring 1 cm or larger underwent total thyroidectomy or lobectomy. Trends in the extent of surgery were examined for patients with papillary thyroid cancer over 2 decades. Logistic regression was used to identify factors that predict the use of total thyroidectomy compared with lobectomy. Use of total thyroidectomy increased from 70.8% in 1985 to 90.4% in 2003 (P < .0001). Patients treated at high-volume medical facilities or academic centers were more likely to undergo total thyroidectomy than were patients examined at low-volume medical facilities or community hospitals (P < .0001).[Level of evidence: 3i]
The objective of surgery is to completely remove the primary tumor, while minimizing treatment-related morbidity, and to guide postoperative treatment with radioactive iodine (RAI). The goal of RAI is to ablate the remnant thyroid tissue to improve the specificity of thyroglobulin assays, which allows the detection of persistent disease by follow-up whole-body scanning. For patients undergoing RAI, removal of all normal thyroid tissue is an important surgical objective. Additionally, for accurate long-term surveillance, RAI whole-body scanning and measurement of serum thyroglobulin are affected by residual, normal thyroid tissue, and in these situations, near total or total thyroidectomy is required. This approach facilitates follow-up thyroid scanning.
I131: Studies have shown that a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas. It may be given in addition to exogenous thyroid hormone but is not considered routine. Patients presenting with papillary thyroid microcarcinomas (tumors <10 mm) have an excellent prognosis when treated surgically, and additional therapy with I131 would not be expected to improve the prognosis.
Thyroid lobectomy alone may be sufficient treatment for small (<1 cm), low-risk, unifocal, intrathyroidal papillary carcinomas in the absence of prior head and neck irradiation or radiologically or clinically involved cervical nodal metastases. This procedure is associated with a lower incidence of complications, but approximately 5% to 10% of patients will have a recurrence in the thyroid following lobectomy. Patients younger than 45 years will have the longest follow-up period and the greatest opportunity for recurrence. Follicular thyroid cancer commonly metastasizes to lungs and bone; with a remnant lobe in place, use of I131 as ablative therapy is compromised. Abnormal regional lymph nodes should be biopsied at the time of surgery. Recognized nodal involvement should be removed at initial surgery, but selective node removal can be performed, and radical neck dissection is usually not required. This results in a decreased recurrence rate but has not been shown to improve survival.
Following the surgical procedure, patients should receive postoperative treatment with exogenous thyroid hormone in doses sufficient to suppress thyroid-stimulating hormone (TSH); studies have shown a decreased incidence of recurrence when TSH is suppressed.
I131: Studies have shown that a postoperative course of therapeutic (ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary and follicular carcinomas. For optimal treatment with RAI, total thyroidectomy is recommended with minimal thyroid remnant remaining. With a large thyroid remnant, a low thyroglobulin level cannot be achieved, which increases the chance of requiring multiple doses of RAI.
Consideration of RAI for remnant ablation is based on pathological risk features including:
RAI may be given with one of two methods of thyrotropin stimulation: withdrawal of thyroid hormone or recombinant human thyrotropin (rhTSH). Administered rhTSH maintains quality of life and reduces the radiation dose delivered to the body compared with thyroid hormone withdrawal. Patients presenting with papillary thyroid microcarcinomas (tumors <10 mm), which are considered to be very low risk, have an excellent prognosis when treated surgically, and additional therapy with I131 would not be expected to improve the prognosis.
The role of RAI in low-risk patients is not clear because disease-free survival (DFS) or overall survival (OS) benefits have not been demonstrated. One study reviewed 1,298 patients from the French Thyroid Cancer Registry. Patients were identified as having low-risk papillary or follicular cancer as they are defined by the American Thyroid Association and the European Thyroid Association criteria:
Of the 1,298 patients, 911 patients received RAI after surgery, and 387 patients did not receive RAI after surgery. Follow-up period was 10.3 years; in multivariate analyses, there were no differences in OS (P = .243) or DFS (P = .2659), according to RAI use.
Long-term complications of RAI using I131 include second malignancies, sialadenitis, and lacrimal and salivary gland dysfunction. Options for reducing the amount of radiation exposure by reducing the amount of RAI in each dose and also to give RAI in combination with rhTSH injections have been explored for low-risk thyroid cancer patients.
Two phase III, randomized, noninferiority studies of patients with low-risk thyroid cancer using a comparison of two thyrotropin-stimulation methods (thyroid hormone withdrawal or use of rhTSH) and two doses of radioiodine I131 1.1GBq [30mCi] and 3.7GBq [100mCi] using a 2 × 2 factorial design showed equivalent thyroid ablation rates between high and low dose I131 at 6 to 10 months after administration of I131.[15,16][Levels of evidence: 3iA and 3iDii] However, differences in the inclusion criteria in one study  consisted of a low-risk, homogeneous cohort in which all of the patients underwent total thyroidectomy, and had pathological TNM stage pT1 ( ≤1 cm) and N1 or Nx, pT1 (>1–2cm) and any N stage, or pT2N0 without thyroid capsule extension/distant metastases. Complete thyroid ablation rate in this study was 92%. Patients undergoing thyroid hormone withdrawal had greater symptoms of hypothyroidism associated with deterioration in quality of life compared with the rhTSH group.
In the other study, patients with more advanced T stage (T1–T3, N0–1) and with less than a total thyroidectomy were included with a lower overall ablation rate of 85%. Neither study assessed the effect of low-dose RAI on long-term recurrences or survival. The studies also did not address whether RAI could be safely omitted in specific low-risk groups.
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I papillary thyroid cancer, stage I follicular thyroid cancer, stage II papillary thyroid cancer and stage II follicular thyroid cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III papillary thyroid cancer and stage III follicular thyroid cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
The most common sites of metastases are lymph nodes, lung, and bone. Treatment of lymph node metastases alone is often curative. Treatment of distant metastases is usually not curative but may produce significant palliation.
Standard treatment options for iodine-sensitive thyroid cancer:
Standard treatment options for iodine-resistant thyroid cancer:
Patients unresponsive to I131 should also be considered candidates for clinical trials testing new approaches to this disease.
Treatment options under clinical evaluation:
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IV papillary thyroid cancer and stage IV follicular thyroid cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Medullary thyroid cancer (MTC) comprises 3% to 4% of all thyroid cancers. These tumors usually present as a mass in the neck or thyroid, often associated with lymphadenopathy, or they may be diagnosed through screening family members. MTC can also be diagnosed by fine-needle aspiration biopsy. Cytology typically reveals hypercellular tumors with spindle-shaped cells and poor adhesion.
The overall survival of patients with MTC is 86% at 5 years and 65% at 10 years. Poor prognostic factors include advanced age, advanced stage, prior neck surgery, and associated multiple endocrine neoplasia (MEN) 2B.[2,3,4]
Approximately 25% of reported cases of MTC are familial. Familial MTC syndromes include MEN 2A, which is the most common; MEN 2B; and familial non-MEN syndromes. (Refer to the PDQ summary on Genetics of Endocrine and Neuroendocrine Neoplasias for more information.) Any patient with a familial variant should be screened for other associated endocrine tumors, particularly parathyroid hyperplasia and pheochromocytoma. MTC can secrete calcitonin and other peptide substances. Determining the level of calcitonin is useful for diagnostic purposes and for following the results of treatment.
Family members should be screened for calcitonin elevation and/or for the RET proto-oncogene mutation to identify other individuals at risk for developing familial MTC. All patients with MTC (whether familial or sporadic) should be tested for RET mutations, and if they are positive, family members should also be tested. Whereas modest elevation of calcitonin may lead to a false-positive diagnosis of medullary carcinoma, DNA testing for the RET mutation is the optimal approach. Family members who are gene carriers should undergo prophylactic thyroidectomy at an early age.[5,6]
Treatment options for localized disease:
Patients with MTC should be treated with a total thyroidectomy, unless there is evidence of distant metastasis. In patients with clinically palpable MTC, the incidence of microscopically positive nodes is more than 75%; routine central and bilateral modified neck dissections have been recommended. When cancer is confined to the thyroid gland, the prognosis is excellent.
External Radiation Therapy
External radiation therapy has been used for palliation of locally recurrent tumors; however, no evidence exists that it provides any survival advantage. Radioactive iodine has no place in the treatment of patients with MTC.
Treatment options for locally advanced and metastatic disease:
Vandetanib is an oral inhibitor of RET kinase, vascular endothelial growth-factor receptor, and epidermal growth-factor receptor signaling. It was tested in a placebo-controlled, prospective trial (NCT00410761) in 331 patients with locally advanced and metastatic disease with a 2:1 ratio in assignment to the study drug. With a median follow-up of 24 months, progression-free survival (PFS) favored vandetanib (hazard ratio = 0.46; 95% confidence interval, 0.31–0.69; P < .001) with a median PFS estimated at 30.5 months for vandetanib versus 19.3 months for placebo.[Level of evidence: 1iiDiii]
Overall survival (OS) was not different at 24 months; longer follow-up will be required since only 47 patients had died at the time of analysis, and there was a crossover to the study drug on progression from placebo, making analysis of OS problematic. Vandetanib has significant side effects, including diarrhea, rash, hypertension, and QT prolongation. Quality of life was not formally assessed in this trial.
Palliative chemotherapy has been reported to produce occasional responses in patients with metastatic disease.[10,11,12,13] No single drug regimen can be considered standard. Some patients with distant metastases will experience prolonged survival and can be managed expectantly until they become symptomatic.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with thyroid gland medullary carcinoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Standard treatment options:
Tracheostomy is frequently necessary. If the disease is confined to the local area, which is rare, total thyroidectomy is warranted to reduce symptoms caused by the tumor mass.[1,2]
External-beam radiation therapy may be used in patients who are not surgical candidates or whose tumor cannot be surgically excised.
Anaplastic thyroid cancer is not responsive to I131 therapy; treatment with individual anticancer drugs has been reported to produce partial remissions in some patients. Approximately 30% of patients achieve a partial remission with doxorubicin. The combination of doxorubicin plus cisplatin appears to be more active than doxorubicin alone and has been reported to produce more complete responses.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with anaplastic thyroid cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Patients treated for differentiated thyroid cancer should be followed carefully with physical examinations, serum quantitative thyroglobulin levels, and radiologic studies based on individual risk for recurrent disease. Approximately 10% to 30% of patients thought to be disease free after initial treatment will develop recurrence and/or metastases. Of these patients, approximately 80% develop recurrence with disease in the neck alone, and 20% develop recurrence with distant metastases. The most common site of distant metastasis is the lung. In a single series of 289 patients who developed recurrences after initial surgery, 16% died of cancer at a median time of 5 years following recurrence.
The prognosis for patients with clinically detectable recurrences is generally poor, regardless of cell type. Those patients who recur with local or regional tumor detected only by I131 scan, however, have a better prognosis. The selection of further treatment depends on many factors, including cell type, uptake of I131, prior treatment, site of recurrence, and individual patient considerations. Surgery with or without I131 ablation can be useful in controlling local recurrences, regional node metastases, or, occasionally, metastases at other localized sites. Approximately 50% of the patients operated on for recurrent tumors can be rendered free of disease with a second operation. Local and regional recurrences detected by I131 scan and not clinically apparent can be treated with I131 ablation and have an excellent prognosis.
Up to 25% of recurrences and metastases from well-differentiated thyroid cancer may not show I131 uptake. For these patients, other imaging techniques shown to be of value include imaging with thallium-201, magnetic resonance imaging, and pentavalent dimercaptosuccinic acid. When recurrent disease does not concentrate I131, or disease recurs after I131 ablation, sorafenib has been approved by the U.S. Food and Drug Administration as a treatment option.
A phase III randomized, double-blind, placebo-controlled study (DECISION [NCT00984282]) evaluated the activity of sorafenib, an orally active, multityrosine kinase inhibitor in patients with progressive iodine-refractory differentiated thyroid cancer. In the trial, 417 patients with locally advanced or metastatic radioactive iodine-refractory thyroid cancer (papillary, follicular [including Hürthle cell], and poorly differentiated varieties) who had progressed within the past 14 months were randomly assigned to sorafenib (400 mg twice daily) versus placebo. Prior chemotherapy, thalidomide, or targeted therapy were excluded.[Level of evidence: 1iDiii
External-beam or intraoperative radiation therapy can be useful in controlling symptoms related to local tumor recurrences. Systemic chemotherapy can be considered. Chemotherapy has been reported to produce occasional objective responses, usually of short duration.[4,10]
Treatment options under clinical evaluation:
Clinical trials evaluating new treatment approaches to this disease should also be considered for these patients. Oral inhibitors of vascular endothelial growth-factor receptors are under clinical evaluation.[Level of evidence: 2Dii]
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent thyroid cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
General Information About Thyroid Cancer
Editorial changes were made to this section.
Stage IV Papillary and Follicular Thyroid Cancer
This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ NCI's Comprehensive Cancer Database pages.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of thyroid cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Thyroid Cancer Treatment are:
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Levels of Evidence
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
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National Cancer Institute: PDQ® Thyroid Cancer Treatment. Bethesda, MD: National Cancer Institute. Date last modified <MM/DD/YYYY>. Available at: http://www.cancer.gov/types/thyroid/hp/thyroid-treatment-pdq. Accessed <MM/DD/YYYY>.
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