Thyroid Cancer

  • Dana-Farber/Brigham and Women's Cancer Care

    Thyroid cancer forms in the thyroid gland, an organ at the base of the throat that makes hormones that help control heart rate, blood pressure, body temperature, and weight. Learn about thyroid cancer and find information on how we support and care for people with thyroid cancer before, during, and after treatment.

Treatment 

The Head and Neck Oncology Program is dedicated exclusively to treating patients with head and neck cancers, which include cancers of the throat, larynx, nose, sinuses, and mouth.

Our specialists evaluate and treat all types and stages, from early lesions to the rarest and most challenging cases.  We also specialize in the treatment of all forms and stages of salivary gland and thyroid cancer.

As a patient, you will be seen by highly experienced clinicians from numerous specialties, including head and neck surgery, medical and radiation oncology, dentistry, oral surgery, reconstructive surgery, nutrition services, social work, speech, voice, and swallowing therapy.

Beginning with the initial consultation, your team of specialists will work with you to create a comprehensive treatment plan tailored to your type of cancer, as well as your lifestyle and personal needs, to achieve the best possible outcome.

Providers meet regularly to discuss new developments in clinical and basic research. The close relationships between world-class researchers and medical clinicians ensure that the latest research findings are translated into new, effective treatment approaches as quickly as possible.

Learn more about treatment and support for patients with head and neck cancers 

Our clinicians are experts in treating all types of head and neck cancers, including: 

  • Hypopharyngeal cancer
  • Laryngeal cancer
  • Nasopharyngeal cancer
  • Oral cancer
  • Oral cavity cancer
  • Oropharyngeal cancer
  • Paranasal sinus and nasal cavity cancer
  • Pharyngeal cancer
  • Laryngeal cancer
  • Lip cancer
  • Ear and Temporal Bone cancer
  • Skull Base cancer
  • Head and Neck Sarcomas
  • Mandible and jaw cancer
  • Adult craniopharyngioma
  • Unknown primary cancer
  • Merkel cell carcinoma
  • Head and Neck Melanoma
  • Salivary gland cancer
  • Parotid gland cancer
  • Acinic cell cancer
  • Adenoidcystic carcinoma
  • Mucoepidermoid cancer
  • Adenocarcinoma cancer
  • Papillary thyroid cancer
  • Follicular thyroid cancer
  • Anaplastic thyroid cancer
  • Medullary thyroid cancer
  • Hurthle cell cancer

Contact us 

New patients 

If you have never been seen before at Dana-Farber/Brigham and Women’s Cancer Center, please call 877-442-3324 or use this online form to make an appointment.

For all other inquiries, please call 617-632-3090

Referring physicians: 617-632-6869

Fax: 617-632-4448

Mailing address
Head and Neck Oncology Center
Dana-Farber Cancer Institute
450 Brookline Ave.
Boston, MA 02115-5450

Information for: Patients | Healthcare Professionals

General Information About Thyroid Cancer

Thyroid cancer is a disease in which malignant (cancer) cells form in the tissues of the thyroid gland.

The thyroid is a gland at the base of the throat near the trachea (windpipe). It is shaped like a butterfly, with a right lobe and a left lobe. The isthmus, a thin piece of tissue, connects the two lobes. A healthy thyroid is a little larger than a quarter. It usually cannot be felt through the skin.

Anatomy of the thyroid and parathyroid glands; drawing shows the thyroid gland at the base of the throat near the trachea. An inset shows the front and back views. The front view shows that the thyroid is shaped like a butterfly, with the right lobe and left lobe connected by a thin piece of tissue called the isthmus. The back view shows the four pea-sized parathyroid glands. The larynx is also shown.
Anatomy of the thyroid and parathyroid glands. The thyroid gland lies at the base of the throat near the trachea. It is shaped like a butterfly, with the right lobe and left lobe connected by a thin piece of tissue called the isthmus. The parathyroid glands are four pea-sized organs found in the neck near the thyroid. The thyroid and parathyroid glands make hormones.

The thyroid uses iodine, a mineral found in some foods and in iodized salt, to help make several hormones. Thyroid hormones do the following:

  • Control heart rate, body temperature, and how quickly food is changed into energy (metabolism).
  • Control the amount of calcium in the blood.

There are four main types of thyroid cancer:

  • Papillary thyroid cancer: The most common type of thyroid cancer.
  • Follicular thyroid cancer. Hürthle cellcarcinoma is a form of follicular thyroid cancer and is treated the same way.
  • Medullary thyroid cancer.
  • Anaplastic thyroid cancer.

See the PDQ summary on Unusual Cancers of Childhood for information about childhood thyroid cancer.

Age, gender, and exposure to radiation can affect the risk of thyroid cancer.

Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn’t mean that you will not get cancer. Talk with your doctor if you think you may be at risk. Risk factors for thyroid cancer include the following:

  • Being between 25 and 65 years old.
  • Being female.
  • Being exposed to radiation to the head and neck as a child or being exposed to radiation from an atomic bomb. The cancer may occur as soon as 5 years after exposure.
  • Having a history of goiter (enlarged thyroid).
  • Having a family history of thyroid disease or thyroid cancer.
  • Having certain geneticconditions such as familial medullary thyroid cancer (FMTC), multiple endocrine neoplasia type 2A syndrome, and multiple endocrine neoplasia type 2B syndrome.
  • Being Asian.

Medullary thyroid cancer is sometimes caused by a change in a gene that is passed from parent to child.

The genes in cells carry hereditary information from parent to child. A certain change in a gene that is passed from parent to child (inherited) may cause medullary thyroid cancer. A test has been developed that can find the changed gene before medullary thyroid cancer appears. The patient is tested first to see if he or she has the changed gene. If the patient has it, other family members may also be tested. Family members, including young children, who have the changed gene can decrease the chance of developing medullary thyroid cancer by having a thyroidectomy (surgery to remove the thyroid).

Possible signs of thyroid cancer include a swelling or lump in the neck.

Thyroid cancer may not cause early symptoms. It is sometimes found during a routine physical exam. Symptoms may occur as the tumor gets bigger. Other conditions may cause the same symptoms. Check with your doctor if you have any of the following problems:

  • A lump in the neck.
  • Trouble breathing.
  • Trouble swallowing.
  • Hoarseness.

Tests that examine the thyroid, neck, and blood are used to detect (find) and diagnose thyroid cancer.

The following tests and procedures may be used:

  • Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or swelling in the neck, voice box, and lymph nodes, and anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.
  • Laryngoscopy: A procedure in which the doctor checks the larynx (voice box) with a mirror or with a laryngoscope. A laryngoscope is a thin, tube-like instrument with a light and a lens for viewing. A thyroid tumor may press on vocal cords. The laryngoscopy is done to see if the vocal cords are moving normally.
  • Blood hormone studies: A procedure in which a blood sample is checked to measure the amounts of certain hormones released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease in the organ or tissue that makes it. The blood may be checked for abnormal levels of thyroid-stimulating hormone (TSH). TSH is made by the pituitary gland in the brain. It stimulates the release of thyroid hormone and controls how fast follicular thyroid cells grow. The blood may also be checked for high levels of the hormone calcitonin and antithyroid antibodies.
  • Blood chemistry studies: A procedure in which a blood sample is checked to measure the amounts of certain substances, such as calcium, released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease in the organ or tissue that makes it.
  • Ultrasound exam: A procedure in which high-energy sound waves (ultrasound) are bounced off internal tissues or organs and make echoes. The echoes form a picture of body tissues called a sonogram. The picture can be printed to be looked at later. This procedure can show the size of a thyroid tumor and whether it is solid or a fluid-filled cyst. Ultrasound may be used to guide a fine-needle aspiration biopsy.
  • CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
  • Fine-needle aspiration biopsy of the thyroid: The removal of thyroid tissue using a thin needle. The needle is inserted through the skin into the thyroid. Several tissue samples are removed from different parts of the thyroid. A pathologist views the tissue samples under a microscope to look for cancer cells. Because the type of thyroid cancer can be hard to diagnose, patients should ask to have biopsy samples checked by a pathologist who has experience diagnosing thyroid cancer.
  • Surgical biopsy: The removal of the thyroid nodule or one lobe of the thyroid during surgery so the cells and tissues can be viewed under a microscope by a pathologist to check for signs of cancer. Because the type of thyroid cancer can be hard to diagnose, patients should ask to have biopsy samples checked by a pathologist who has experience diagnosing thyroid cancer.

Certain factors affect prognosis (chance of recovery) and treatment options.

The prognosis (chance of recovery) and treatment options depend on the following:

  • The age of the patient.
  • The type of thyroid cancer.
  • The stage of the cancer.
  • The patient's general health.
  • Whether the patient has multiple endocrine neoplasia type 2B (MEN 2B).
  • Whether the cancer has just been diagnosed or has recurred (come back).

Stages of Thyroid Cancer

After thyroid cancer has been diagnosed, tests are done to find out if cancer cells have spread within the thyroid or to other parts of the body.

The process used to find out if cancer has spread within the thyroid or to other parts of the body is called staging. The information gathered from the staging process determines the stage of the disease. It is important to know the stage in order to plan treatment. The following tests and procedures may be used in the staging process:

  • CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
  • Ultrasound exam: A procedure in which high-energy sound waves (ultrasound) are bounced off internal tissues or organs and make echoes. The echoes form a picture of body tissues called a sonogram. The picture can be printed to be looked at later.
  • Chest x-ray: An x-ray of the organs and bones inside the chest. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body.
  • Sentinel lymph node biopsy: The removal of the sentinel lymph node during surgery. The sentinel lymph node is the first lymph node to receive lymphatic drainage from a tumor. It is the first lymph node the cancer is likely to spread to from the tumor. A radioactive substance and/or blue dye is injected near the tumor. The substance or dye flows through the lymph ducts to the lymph nodes. The first lymph node to receive the substance or dye is removed. A pathologist views the tissue under a microscope to look for cancer cells. If cancer cells are not found, it may not be necessary to remove more lymph nodes.

There are three ways that cancer spreads in the body.

The three ways that cancer spreads in the body are:

  • Through tissue. Cancer invades the surrounding normal tissue.
  • Through the lymph system. Cancer invades the lymph system and travels through the lymph vessels to other places in the body.
  • Through the blood. Cancer invades the veins and capillaries and travels through the blood to other places in the body.

When cancer cells break away from the primary (original) tumor and travel through the lymph or blood to other places in the body, another (secondary) tumor may form. This process is called metastasis. The secondary (metastatic) tumor is the same type of cancer as the primary tumor. For example, if breast cancer spreads to the bones, the cancer cells in the bones are actually breast cancer cells. The disease is metastatic breast cancer, not bone cancer.

The following stages are used for papillary and follicular thyroid cancer in patients younger than 45 years:

Stage I

In stage I papillary and follicular thyroid cancer, the tumor is any size, may be in the thyroid, or may have spread to nearby tissues and lymph nodes. Cancer has not spread to other parts of the body.

Stage II

In stage II papillary and follicular thyroid cancer, the tumor is any size and cancer has spread from the thyroid to other parts of the body, such as the lungs or bone, and may have spread to lymph nodes.

The following stages are used for papillary and follicular thyroid cancer in patients 45 years and older:

Tumor size compared to everyday objects; shows various measurements of a tumor compared to a pea, peanut, walnut, and lime
Pea, peanut, walnut, and lime show tumor sizes.

Stage I

In stage I papillary and follicular thyroid cancer, cancer is found only in the thyroid and the tumor is 2 centimeters or smaller.

Stage II

In stage II papillary and follicular thyroid cancer, cancer is only in the thyroid and the tumor is larger than 2 centimeters but not larger than 4 centimeters.

Stage III

In stage III papillary and follicular thyroid cancer, either of the following is found:

  • the tumor is larger than 4 centimeters and only in the thyroid or the tumor is any size and cancer has spread to tissues just outside the thyroid, but not to lymph nodes; or
  • the tumor is any size and cancer may have spread to tissues just outside the thyroid and has spread to lymph nodes near the trachea or the larynx (voice box).

Stage IV

Stage IV papillary and follicular thyroid cancer is divided into stages IVA, IVB, and IVC.

  • In stage IVA, either of the following is found:
    • the tumor is any size and cancer has spread outside the thyroid to tissues under the skin, the trachea, the esophagus, the larynx (voice box), and/or the recurrentlaryngealnerve (a nerve with two branches that go to the larynx); cancer may have spread to nearby lymph nodes; or
    • the tumor is any size and cancer may have spread to tissues just outside the thyroid. Cancer has spread to lymph nodes on one or both sides of the neck or between the lungs.
  • In stage IVB, cancer has spread to tissue in front of the spinal column or has surrounded the carotid artery or the blood vessels in the area between the lungs; cancer may have spread to lymph nodes.
  • In stage IVC, the tumor is any size and cancer has spread to other parts of the body, such as the lungs and bones, and may have spread to lymph nodes.

The following stages are used for medullary thyroid cancer:

Stage 0

Stage 0 medullary thyroid cancer is found only with a special screening test. No tumor can be found in the thyroid.

Stage I

Stage I medullary thyroid cancer is found only in the thyroid and is 2 centimeters or smaller.

Stage II

In stage II medullary thyroid cancer, either of the following is found:

  • the tumor is larger than 2 centimeters and only in the thyroid; or
  • the tumor is any size and has spread to tissues just outside the thyroid, but not to lymph nodes.

Stage III

In stage III medullary thyroid cancer, the tumor is any size, has spread to lymph nodes near the trachea and the larynx (voice box), and may have spread to tissues just outside the thyroid.

Stage IV

Stage IV medullary thyroid cancer is divided into stages IVA, IVB, and IVC.

  • In stage IVA, either of the following is found:
    • the tumor is any size and cancer has spread outside the thyroid to tissues under the skin, the trachea, the esophagus, the larynx (voice box), and/or the recurrent laryngealnerve (a nerve with 2 branches that go to the larynx); cancer may have spread to lymph nodes near the trachea or the larynx; or
    • the tumor is any size and cancer may have spread to tissues just outside the thyroid. Cancer has spread to lymph nodes on one or both sides of the neck or between the lungs.
  • In stage IVB, cancer has spread to tissue in front of the spinal column or has surrounded the carotid artery or the blood vessels in the area between the lungs. Cancer may have spread to lymph nodes.
  • In stage IVC, the tumor is any size and cancer has spread to other parts of the body, such as the lungs and bones, and may have spread to lymph nodes.

Anaplastic thyroid cancer is considered stage IV thyroid cancer.

Anaplastic thyroid cancer grows quickly and has usually spread within the neck when it is found. Stage IV anaplastic thyroid cancer is divided into stages IVA, IVB, and IVC.

  • In stage IVA, cancer is found in the thyroid and may have spread to lymph nodes.
  • In stage IVB, cancer has spread to tissue just outside the thyroid and may have spread to lymph nodes.
  • In stage IVC, cancer has spread to other parts of the body, such as the lungs and bones, and may have spread to lymph nodes.

Recurrent Thyroid Cancer

Recurrentthyroid cancer is cancer that has recurred (come back) after it has been treated. Thyroid cancer may come back in the thyroid or in other parts of the body.

Treatment Option Overview

There are different types of treatment for patients with thyroid cancer.

Different types of treatment are available for patients with thyroid cancer. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.

Five types of standard treatment are used:

Surgery

Surgery is the most common treatment of thyroid cancer. One of the following procedures may be used:

  • Lobectomy: Removal of the lobe in which thyroid cancer is found. Biopsies of lymph nodes in the area may be done to see if they contain cancer.
  • Near-total thyroidectomy: Removal of all but a very small part of the thyroid.
  • Total thyroidectomy: Removal of the whole thyroid.
  • Lymphadenectomy: Removal of lymph nodes in the neck that contain cancer.

Radiation therapy, including radioactive iodine therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. The way the radiation therapy is given depends on the type and stage of the cancer being treated.

Radiation therapy may be given after surgery to kill any thyroid cancer cells that were not removed. Follicular and papillary thyroid cancers are sometimes treated with radioactive iodine (RAI) therapy. RAI is taken by mouth and collects in any remaining thyroid tissue, including thyroid cancer cells that have spread to other places in the body. Since only thyroid tissue takes up iodine, the RAI destroys thyroid tissue and thyroid cancer cells without harming other tissue. Before a full treatment dose of RAI is given, a small test-dose is given to see if the tumor takes up the iodine.

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). The way the chemotherapy is given depends on the type and stage of the cancer being treated.

See Drugs Approved for Thyroid Cancer for more information.

Thyroid hormone therapy

Hormone therapy is a cancer treatment that removes hormones or blocks their action and stops cancer cells from growing. Hormones are substances made by glands in the body and circulated in the bloodstream. In the treatment of thyroid cancer, drugs may be given to prevent the body from making thyroid-stimulating hormone (TSH), a hormone that can increase the chance that thyroid cancer will grow or recur.

Also, because thyroid cancer treatment kills thyroid cells, the thyroid is not able to make enough thyroid hormone. Patients are given thyroid hormone replacement pills.

Targeted therapy

Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells without harming normal cells. Tyrosine kinase inhibitor (TKI) therapy is a type of targeted therapy that blocks signals needed for tumors to grow. Vandetanib is a TKI used to treat thyroid cancer.

See Drugs Approved for Thyroid Cancer for more information.

New types of treatment are being tested in clinical trials.

Information about clinical trials is available from the NCI Web site.

Patients may want to think about taking part in a clinical trial.

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Patients can enter clinical trials before, during, or after starting their cancer treatment.

Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.

Clinical trials are taking place in many parts of the country. See the Treatment Options section that follows for links to current treatment clinical trials. These have been retrieved from NCI's listing of clinical trials.

Follow-up tests may be needed.

Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests. This is sometimes called re-staging.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.

Treatment Options by Stage

A link to a list of current clinical trials is included for each treatment section. For some types or stages of cancer, there may not be any trials listed. Check with your doctor for clinical trials that are not listed here but may be right for you.

Stages I and II Papillary and Follicular Thyroid Cancer

Treatment of stage I and II papillary and follicular thyroid cancer may include the following:

  • Total or near-total thyroidectomy, with or without radioactive iodinetherapy.
  • Lobectomy and removal of lymph nodes that contain cancer, followed by hormone therapy. Radioactive iodine therapy may be given following surgery.

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. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.

Stage III Papillary and Follicular Thyroid Cancer

Treatment of stage III papillary and follicular thyroid cancer is usually total thyroidectomy. Cancer that has spread outside the thyroid, as well as any lymph nodes that have cancer in them, will also be removed. Radioactive iodinetherapy or external radiation therapy may be given after surgery.

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. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.

Stage IV Papillary and Follicular Thyroid Cancer

Treatment of stage IV papillary and follicular thyroid cancer that has spread only to the lymph nodes can often be cured. When cancer has spread to other places in the body, such as the lungs and bone, treatment usually does not cure the cancer, but can relieve symptoms and improve the quality of life. Treatment may include the following:

  • Radioactive iodinetherapy.
  • External-beam radiation therapy.
  • Surgery to remove cancer from areas where it has spread.
  • Hormone therapy.
  • A clinical trial of chemotherapy.
  • A clinical trial of a targeted therapy.

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. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.

Medullary Thyroid Cancer

Treatment may include the following:

  • Total thyroidectomy if the cancer has not spread to other parts of the body.
  • Removal of lymph nodes that contain cancer.
  • External radiation therapy as palliative therapy to relieve symptoms and improve the quality of life for patients whose cancer has recurred in the thyroid.
  • Targeted therapy with a tyrosine kinase inhibitor for cancer that has spread to other parts of the body.
  • Chemotherapy as palliative therapy to relieve symptoms and improve the quality of life for patients whose cancer has spread to other parts of the body.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with thyroid gland medullary carcinoma. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.

Anaplastic Thyroid Cancer

Treatment may include the following:

  • Tracheostomy as palliative therapy to relieve symptoms and improve the quality of life.
  • Total thyroidectomy as palliative therapy to relieve symptoms and improve the quality of life for patients whose cancer has not spread away from the thyroid.
  • External radiation therapy.
  • Chemotherapy.
  • A clinical trial of total thyroidectomy followed by chemotherapy and radiation therapy.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with anaplastic thyroid cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.

Treatment Options for Recurrent Thyroid Cancer

Treatment of recurrentthyroid cancer may include the following:

  • Surgery with or without radioactive iodinetherapy.
  • Radioactive iodine therapy when the cancer can be found only by a thyroidscan and cannot be felt during a physical exam.
  • External radiation therapy or intraoperative radiation therapy as palliative therapy to relieve symptoms and improve the quality of life.
  • Chemotherapy.
  • A clinical trial of a targeted therapy.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent thyroid cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.

To Learn More About Thyroid Cancer

For more information from the National Cancer Institute about thyroid cancer, see the following:

For general cancer information and other resources from the National Cancer Institute, see the following:

About PDQ

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PDQ is the National Cancer Institute's (NCI's) comprehensive cancer information database. Most of the information contained in PDQ is available online at NCI's Web site. PDQ is provided as a service of the NCI. The NCI is part of the National Institutes of Health, the federal government's focal point for biomedical research.

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A clinical trial is a study to answer a scientific question, such as whether one treatment is better than another. Trials are based on past studies and what has been learned in the laboratory. Each trial answers certain scientific questions in order to find new and better ways to help cancer patients. During treatment clinical trials, information is collected about the effects of a new treatment and how well it works. If a clinical trial shows that a new treatment is better than one currently being used, the new treatment may become "standard." Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.

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This information is provided by the National Cancer Institute.

This information was last updated on January 11, 2013.


General Information About Thyroid Cancer

Incidence and Mortality

Estimated new cases and deaths from thyroid cancer in the United States in 2013:[1]

  • New cases: 60,220.
  • Deaths: 1,850.

Carcinoma of the thyroid gland is an uncommon cancer but is the most common malignancy of the endocrine system.[2] 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]

Risk Factors

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.[5] 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:[9]

  • A history of goiter.
  • Family history of thyroid disease.
  • Female gender.
  • Asian race.

Prognostic Factors

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.[12] 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.[15] 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.[20]

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.[21] 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.[24] Expression of the tumor suppressor gene p53 has also been associated with an adverse prognosis for patients with thyroid cancer.[25]

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.[11] 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.[11] 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.[2]

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.

Related Summaries

Other PDQ summaries containing information related to thyroid cancer include the following:

  • Genetics of Medullary Thyroid Cancer
  • Unusual Cancers of Childhood (childhood cancer of the thyroid)

References:

  1. American Cancer Society.: Cancer Facts and Figures 2013. Atlanta, Ga: American Cancer Society, 2013. Available online. Last accessed February 8, 2013.

  2. Hundahl SA, Fleming ID, Fremgen AM, et al.: A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985-1995 [see comments] Cancer 83 (12): 2638-48, 1998.

  3. Tennvall J, Biörklund A, Möller T, et al.: Is the EORTC prognostic index of thyroid cancer valid in differentiated thyroid carcinoma? Retrospective multivariate analysis of differentiated thyroid carcinoma with long follow-up. Cancer 57 (7): 1405-14, 1986.

  4. Khoo ML, Asa SL, Witterick IJ, et al.: Thyroid calcification and its association with thyroid carcinoma. Head Neck 24 (7): 651-5, 2002.

  5. Carling T, Udelsman R: Thyroid tumors. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1457-72.

  6. Pacini F, Vorontsova T, Molinaro E, et al.: Prevalence of thyroid autoantibodies in children and adolescents from Belarus exposed to the Chernobyl radioactive fallout. Lancet 352 (9130): 763-6, 1998.

  7. Cardis E, Kesminiene A, Ivanov V, et al.: Risk of thyroid cancer after exposure to 131I in childhood. J Natl Cancer Inst 97 (10): 724-32, 2005.

  8. Tronko MD, Howe GR, Bogdanova TI, et al.: A cohort study of thyroid cancer and other thyroid diseases after the chornobyl accident: thyroid cancer in Ukraine detected during first screening. J Natl Cancer Inst 98 (13): 897-903, 2006.

  9. Iribarren C, Haselkorn T, Tekawa IS, et al.: Cohort study of thyroid cancer in a San Francisco Bay area population. Int J Cancer 93 (5): 745-50, 2001.

  10. Grant CS, Hay ID, Gough IR, et al.: Local recurrence in papillary thyroid carcinoma: is extent of surgical resection important? Surgery 104 (6): 954-62, 1988.

  11. Sanders LE, Cady B: Differentiated thyroid cancer: reexamination of risk groups and outcome of treatment. Arch Surg 133 (4): 419-25, 1998.

  12. Mazzaferri EL: Treating differentiated thyroid carcinoma: where do we draw the line? Mayo Clin Proc 66 (1): 105-11, 1991.

  13. Staunton MD: Thyroid cancer: a multivariate analysis on influence of treatment on long-term survival. Eur J Surg Oncol 20 (6): 613-21, 1994.

  14. Mazzaferri EL, Jhiang SM: Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med 97 (5): 418-28, 1994.

  15. Shah JP, Loree TR, Dharker D, et al.: Prognostic factors in differentiated carcinoma of the thyroid gland. Am J Surg 164 (6): 658-61, 1992.

  16. Andersen PE, Kinsella J, Loree TR, et al.: Differentiated carcinoma of the thyroid with extrathyroidal extension. Am J Surg 170 (5): 467-70, 1995.

  17. Coburn MC, Wanebo HJ: Prognostic factors and management considerations in patients with cervical metastases of thyroid cancer. Am J Surg 164 (6): 671-6, 1992.

  18. Voutilainen PE, Multanen MM, Leppäniemi AK, et al.: Prognosis after lymph node recurrence in papillary thyroid carcinoma depends on age. Thyroid 11 (10): 953-7, 2001.

  19. Sellers M, Beenken S, Blankenship A, et al.: Prognostic significance of cervical lymph node metastases in differentiated thyroid cancer. Am J Surg 164 (6): 578-81, 1992.

  20. Cunningham DK, Yao KA, Turner RR, et al.: Sentinel lymph node biopsy for papillary thyroid cancer: 12 years of experience at a single institution. Ann Surg Oncol 17 (11): 2970-5, 2010.

  21. Lennard CM, Patel A, Wilson J, et al.: Intensity of vascular endothelial growth factor expression is associated with increased risk of recurrence and decreased disease-free survival in papillary thyroid cancer. Surgery 129 (5): 552-8, 2001.

  22. van Herle AJ, van Herle KA: Thyroglobulin in benign and malignant thyroid disease. In: Falk SA: Thyroid Disease: Endocrinology, Surgery, Nuclear Medicine, and Radiotherapy. Philadelphia, Pa: Lippincott-Raven, 1997, pp 601-618.

  23. Ruiz-Garcia J, Ruiz de Almodóvar JM, Olea N, et al.: Thyroglobulin level as a predictive factor of tumoral recurrence in differentiated thyroid cancer. J Nucl Med 32 (3): 395-8, 1991.

  24. Duren M, Siperstein AE, Shen W, et al.: Value of stimulated serum thyroglobulin levels for detecting persistent or recurrent differentiated thyroid cancer in high- and low-risk patients. Surgery 126 (1): 13-9, 1999.

  25. Godballe C, Asschenfeldt P, Jørgensen KE, et al.: Prognostic factors in papillary and follicular thyroid carcinomas: p53 expression is a significant indicator of prognosis. Laryngoscope 108 (2): 243-9, 1998.

Cellular Classification of Thyroid Cancer

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):[1]

  • Papillary carcinoma.
    • Papillary/follicular carcinoma.
  • Follicular carcinoma.
    • Hürthle cell carcinoma, a variant of follicular carcinoma with a poorer prognosis.[2][3]
  • Medullary carcinoma.
  • Anaplastic carcinoma.
    • Small cell carcinoma.
    • Giant cell carcinoma.
  • Others.
    • Lymphoma.
    • Sarcoma.
    • Carcinosarcoma.

A definition for each major type can be found under stage information.

References:

  1. LiVolsi VA: Pathology of thyroid disease. In: Falk SA: Thyroid Disease: Endocrinology, Surgery, Nuclear Medicine, and Radiotherapy. Philadelphia, Pa: Lippincott-Raven, 1997, pp 127-175.

  2. Kushchayeva Y, Duh QY, Kebebew E, et al.: Comparison of clinical characteristics at diagnosis and during follow-up in 118 patients with Hurthle cell or follicular thyroid cancer. Am J Surg 195 (4): 457-62, 2008.

  3. Mills SC, Haq M, Smellie WJ, et al.: Hürthle cell carcinoma of the thyroid: Retrospective review of 62 patients treated at the Royal Marsden Hospital between 1946 and 2003. Eur J Surg Oncol 35 (3): 230-4, 2009.

Stage Information for Thyroid Cancer

Definitions of TNM

The American Joint Committee on Cancer (AJCC) has designated staging by TNM classification to define thyroid cancer.[1]

Table 1. Primary Tumor (T)a,b

TX

Primary tumor cannot be assessed.

T0

No evidence of primary tumor.

T1

Tumor ≤2 cm in greatest dimension limited to the thyroid.

T1a

Tumor ≤1 cm, limited to the thyroid.

T1b

Tumor >1 cm but ≤2 cm in greatest dimension, limited to the thyroid.

T2

Tumor >2 cm but ≤4 cm in greatest dimension, limited to the thyroid.

T3

Tumor >4 cm in greatest dimension limited to the thyroid or any tumor with minimal extrathyroid extension (e.g., extension to sternothyroid muscle or perithyroid soft tissues).

T4a

Moderately advanced disease.

Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues, larynx, trachea, esophagus, or recurrent laryngeal nerve.

T4b

Very advanced disease.

Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels.

cT4a

Intrathyroidal anaplastic carcinoma.

cT4b

Anaplastic carcinoma with gross extrathyroid extension.

aReprinted with permission from AJCC: Thyroid. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 87-96.

bAll categories may be subdivided: (s) solitary tumor and (m) multifocal tumor (the largest determines the classification).

cAll anaplastic carcinomas are considered T4 tumors.

Table 2. Regional Lymph Nodes (N)a,b

NX

Regional lymph nodes cannot be assessed.

N0

No regional lymph node metastasis.

N1

Regional lymph node metastasis.

N1a

Metastases to Level VI (pretracheal, paratracheal, and prelaryngeal/Delphian lymph nodes).

N1b

Metastases to unilateral, bilateral, or contralateral cervical (Levels I, II, III, IV, or V) or retropharyngeal or superior mediastinal lymph nodes (Level VII).

aReprinted with permission from AJCC: Thyroid. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 87-96.

bRegional lymph nodes are the central compartment, lateral cervical, and upper mediastinal lymph nodes.

Table 3. Distant Metastasis (M)a

M0

No distant metastasis.

M1

Distant metastasis.

aReprinted with permission from AJCC: Thyroid. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 87-96.

Table 4. Anatomic Stage/Prognostic Groupsa,b

Stage

T

N

M

Papillary or follicular (differentiated)

YOUNGER THAN 45 YEARS

I

Any T

Any N

M0

II

Any T

Any N

M1

45 YEARS AND OLDER

I

T1

N0

M0

II

T2

N0

M0

III

T3

N0

M0

T1

N1a

M0

T2

N1a

M0

T3

N1a

M0

IVA

T4a

N0

M0

T4a

N1a

M0

T1

N1b

M0

T2

N1b

M0

T3

N1b

M0

T4a

N1b

M0

IVB

T4b

Any N

M0

Stage IVC

Any T

Any N

M1

Medullary carcinoma (all age groups)

I

T1

N0

M0

II

T2

N0

M0

T3

N0

M0

III

T1

N1a

M0

T1

N1a

M0

T2

N1a

M0

T3

N1a

M0

IVA

T4a

N0

M0

T4a

N1a

M0

T1

N1b

M0

T2

N1b

M0

T3

N1b

M0

T4a

N1b

M0

Stage IVB

T4b

Any N

IVB

T4b

Any N

M0

IVC

Any T

Any N

M1

Anaplastic carcinomac

IVA

T4a

Any N

M0

IVB

T4b

Any N

M0

IVC

Any T

Any N

M1

aReprinted with permission from AJCC: Thyroid. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 87-96.

bSeparate stage groupings are recommended for papillary or follicular (differentiated), medullary, and anaplastic (undifferentiated) carcinoma.

cAll anaplastic carcinomas are considered Stage IV.

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.[2]

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.[3]

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:

  • Stage IVA (moderately advanced with or without lymph node metastases [for T4a] but without distant metastases).
  • Stage IVB (very advanced with or without lymph node metastases but no distant metastases).
  • Stage IVC (distant metastases).

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.[4]

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 elevation of calcitonin may lead to a false-positive diagnosis of medullary carcinoma, DNA testing for the RET 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.[8]

References:

  1. Thyroid. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 87-96.

  2. Haigh PI, Urbach DR: The treatment and prognosis of Hürthle cell follicular thyroid carcinoma compared with its non-Hürthle cell counterpart. Surgery 138 (6): 1152-7; discussion 1157-8, 2005.

  3. Colson YL, Carty SE: Medullary thyroid carcinoma. Am J Otolaryngol 14 (2): 73-81, 1993 Mar-Apr.

  4. Carling T, Udelsman R: Thyroid tumors. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1457-72.

  5. Lips CJ, Landsvater RM, Höppener JW, et al.: Clinical screening as compared with DNA analysis in families with multiple endocrine neoplasia type 2A. N Engl J Med 331 (13): 828-35, 1994.

  6. Decker RA, Peacock ML, Borst MJ, et al.: Progress in genetic screening of multiple endocrine neoplasia type 2A: is calcitonin testing obsolete? Surgery 118 (2): 257-63; discussion 263-4, 1995.

  7. Skinner MA, Moley JA, Dilley WG, et al.: Prophylactic thyroidectomy in multiple endocrine neoplasia type 2A. N Engl J Med 353 (11): 1105-13, 2005.

  8. Neff RL, Farrar WB, Kloos RT, et al.: Anaplastic thyroid cancer. Endocrinol Metab Clin North Am 37 (2): 525-38, xi, 2008.

Stage I and II Papillary and Follicular Thyroid Cancer

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:

  1. Total thyroidectomy.
  2. Lobectomy.

Total Thyroidectomy

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).[8] 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.[8][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 wtih 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).[9][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.[4] It may be given in addition to exogenous thyroid hormone but is not considered routine.[10] 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.[11]

Lobectomy

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.[12] 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.[4] 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:

  • Evaluation of the size of the primary tumor.
  • The presence of lymphovascular invasion.
  • Capsule invasion.
  • The number of involved lymph nodes.

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.[13] 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.[11]

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.[14] 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:

  • Complete tumor resection.
  • Multifocal pT1 <1 cm.
  • pT1 >1 cm.
  • pT2, pN0, pM0 (American Joint Committee on Cancer/Union Internationale Contre le Cancer [AJCC/UICC]) corresponds to stage I for patients <45 years old.
  • pT2, pN0, pM0 (AJCC/UICC) corresponds to stages 1 and 2 for patients >45 years old.
  • pT1 and pT2 without lymph node dissection (Nx).

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.[14]

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 and3iDii] However, differences in the inclusion criteria in one study [15] 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,[16] 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.

References:

  1. Carling T, Udelsman R: Thyroid tumors. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1457-72.

  2. Grant CS, Hay ID, Gough IR, et al.: Local recurrence in papillary thyroid carcinoma: is extent of surgical resection important? Surgery 104 (6): 954-62, 1988.

  3. Cady B, Rossi R: An expanded view of risk-group definition in differentiated thyroid carcinoma. Surgery 104 (6): 947-53, 1988.

  4. Mazzaferri EL, Jhiang SM: Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med 97 (5): 418-28, 1994.

  5. Staunton MD: Thyroid cancer: a multivariate analysis on influence of treatment on long-term survival. Eur J Surg Oncol 20 (6): 613-21, 1994.

  6. Tollefsen HR, Shah JP, Huvos AG: Follicular carcinoma of the thyroid. Am J Surg 126 (4): 523-8, 1973.

  7. Edis AJ: Surgical treatment for thyroid cancer. Surg Clin North Am 57 (3): 533-42, 1977.

  8. Bilimoria KY, Bentrem DJ, Ko CY, et al.: Extent of surgery affects survival for papillary thyroid cancer. Ann Surg 246 (3): 375-81; discussion 381-4, 2007.

  9. Bilimoria KY, Bentrem DJ, Linn JG, et al.: Utilization of total thyroidectomy for papillary thyroid cancer in the United States. Surgery 142 (6): 906-13; discussion 913.e1-2, 2007.

  10. Beierwaltes WH, Rabbani R, Dmuchowski C, et al.: An analysis of "ablation of thyroid remnants" with I-131 in 511 patients from 1947-1984: experience at University of Michigan. J Nucl Med 25 (12): 1287-93, 1984.

  11. Hay ID, Grant CS, van Heerden JA, et al.: Papillary thyroid microcarcinoma: a study of 535 cases observed in a 50-year period. Surgery 112 (6): 1139-46; discussion 1146-7, 1992.

  12. Hay ID, Grant CS, Bergstralh EJ, et al.: Unilateral total lobectomy: is it sufficient surgical treatment for patients with AMES low-risk papillary thyroid carcinoma? Surgery 124 (6): 958-64; discussion 964-6, 1998.

  13. Hänscheid H, Lassmann M, Luster M, et al.: Iodine biokinetics and dosimetry in radioiodine therapy of thyroid cancer: procedures and results of a prospective international controlled study of ablation after rhTSH or hormone withdrawal. J Nucl Med 47 (4): 648-54, 2006.

  14. Schvartz C, Bonnetain F, Dabakuyo S, et al.: Impact on overall survival of radioactive iodine in low-risk differentiated thyroid cancer patients. J Clin Endocrinol Metab 97 (5): 1526-35, 2012.

  15. Schlumberger M, Catargi B, Borget I, et al.: Strategies of radioiodine ablation in patients with low-risk thyroid cancer. N Engl J Med 366 (18): 1663-73, 2012.

  16. Mallick U, Harmer C, Yap B, et al.: Ablation with low-dose radioiodine and thyrotropin alfa in thyroid cancer. N Engl J Med 366 (18): 1674-85, 2012.

Stage III Papillary and Follicular Thyroid Cancer

Standard treatment options:

  1. Total thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease.
  2. I131 ablation following total thyroidectomy if the tumor demonstrates uptake of this isotope.[1]
  3. External-beam radiation therapy if I131 uptake is minimal.[2]

Current Clinical Trials

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.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Beierwaltes WH, Rabbani R, Dmuchowski C, et al.: An analysis of "ablation of thyroid remnants" with I-131 in 511 patients from 1947-1984: experience at University of Michigan. J Nucl Med 25 (12): 1287-93, 1984.

  2. Simpson WJ, Carruthers JS: The role of external radiation in the management of papillary and follicular thyroid cancer. Am J Surg 136 (4): 457-60, 1978.

Stage IV Papillary and Follicular Thyroid Cancer

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:

  1. I131: Metastases that demonstrate uptake of this isotope may be ablated by therapeutic doses of I131.
  2. External-beam radiation therapy for patients with localized lesions that are unresponsive to I131.[1]
  3. Resection of limited metastases, especially symptomatic metastases, should be considered when the tumor has no uptake of I131.
  4. Thyroid-stimulating hormone suppression with thyroxine is also effective in many lesions not sensitive to I131.

Patients unresponsive to I131 should also be considered candidates for clinical trials testing new approaches to this disease.

Treatment options under clinical evaluation:

  • Clinical trials evaluating new treatment approaches to this disease should also be considered for these patients. Chemotherapy has been reported to produce occasional complete responses of long duration.[2][3][4] Oral inhibitors of vascular endothelial growth-factor receptors are under clinical evaluation.[5][Level of evidence: 2Dii]

Current Clinical Trials

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.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Simpson WJ, Carruthers JS: The role of external radiation in the management of papillary and follicular thyroid cancer. Am J Surg 136 (4): 457-60, 1978.

  2. Gottlieb JA, Hill CS Jr, Ibanez ML, et al.: Chemotherapy of thyroid cancer. An evaluation of experience with 37 patients. Cancer 30 (3): 848-53, 1972.

  3. Harada T, Nishikawa Y, Suzuki T, et al.: Bleomycin treatment for cancer of the thyroid. Am J Surg 122 (1): 53-7, 1971.

  4. Shimaoka K, Schoenfeld DA, DeWys WD, et al.: A randomized trial of doxorubicin versus doxorubicin plus cisplatin in patients with advanced thyroid carcinoma. Cancer 56 (9): 2155-60, 1985.

  5. Sherman SI, Wirth LJ, Droz JP, et al.: Motesanib diphosphate in progressive differentiated thyroid cancer. N Engl J Med 359 (1): 31-42, 2008.

Medullary Thyroid Cancer

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,[1] 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.[2]

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:

  1. Thyroidectomy.
  2. External radiation therapy.

Thyroidectomy

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.[7] 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.[8] Radioactive iodine has no place in the treatment of patients with MTC.

Treatment options for locally advanced and metastatic disease:

  • Palliative chemotherapy.

Palliative Chemotherapy

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.[9] 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.[9][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.[9]

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.

Current Clinical Trials

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.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Soh EY, Clark OH: Surgical considerations and approach to thyroid cancer. Endocrinol Metab Clin North Am 25 (1): 115-39, 1996.

  2. Giuffrida D, Gharib H: Current diagnosis and management of medullary thyroid carcinoma. Ann Oncol 9 (7): 695-701, 1998.

  3. Saad MF, Ordonez NG, Rashid RK, et al.: Medullary carcinoma of the thyroid. A study of the clinical features and prognostic factors in 161 patients. Medicine (Baltimore) 63 (6): 319-42, 1984.

  4. Bergholm U, Bergström R, Ekbom A: Long-term follow-up of patients with medullary carcinoma of the thyroid. Cancer 79 (1): 132-8, 1997.

  5. Lips CJ, Landsvater RM, Höppener JW, et al.: Clinical screening as compared with DNA analysis in families with multiple endocrine neoplasia type 2A. N Engl J Med 331 (13): 828-35, 1994.

  6. Decker RA, Peacock ML, Borst MJ, et al.: Progress in genetic screening of multiple endocrine neoplasia type 2A: is calcitonin testing obsolete? Surgery 118 (2): 257-63; discussion 263-4, 1995.

  7. Moley JF, DeBenedetti MK: Patterns of nodal metastases in palpable medullary thyroid carcinoma: recommendations for extent of node dissection. Ann Surg 229 (6): 880-7; discussion 887-8, 1999.

  8. Brierley JD, Tsang RW: External radiation therapy in the treatment of thyroid malignancy. Endocrinol Metab Clin North Am 25 (1): 141-57, 1996.

  9. Wells SA Jr, Robinson BG, Gagel RF, et al.: Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol 30 (2): 134-41, 2012.

  10. Shimaoka K, Schoenfeld DA, DeWys WD, et al.: A randomized trial of doxorubicin versus doxorubicin plus cisplatin in patients with advanced thyroid carcinoma. Cancer 56 (9): 2155-60, 1985.

  11. De Besi P, Busnardo B, Toso S, et al.: Combined chemotherapy with bleomycin, adriamycin, and platinum in advanced thyroid cancer. J Endocrinol Invest 14 (6): 475-80, 1991.

  12. Wu LT, Averbuch SD, Ball DW, et al.: Treatment of advanced medullary thyroid carcinoma with a combination of cyclophosphamide, vincristine, and dacarbazine. Cancer 73 (2): 432-6, 1994.

  13. Orlandi F, Caraci P, Berruti A, et al.: Chemotherapy with dacarbazine and 5-fluorouracil in advanced medullary thyroid cancer. Ann Oncol 5 (8): 763-5, 1994.

Anaplastic Thyroid Cancer

Standard treatment options:

  1. Surgery.
  2. Radiation therapy.
  3. Chemotherapy.

Surgery

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]

Radiation Therapy

External-beam radiation therapy may be used in patients who are not surgical candidates or whose tumor cannot be surgically excised.

Chemotherapy

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.[3] The combination of doxorubicin plus cisplatin appears to be more active than doxorubicin alone and has been reported to produce more complete responses.[4]

Treatment options under clinical evaluation:

  • The combination of chemotherapy plus radiation therapy in patients following complete resection may provide prolonged survival but has not been compared with any one modality alone.[5][6]

Current Clinical Trials

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.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Goldman JM, Goren EN, Cohen MH, et al.: Anaplastic thyroid carcinoma: long-term survival after radical surgery. J Surg Oncol 14 (4): 389-94, 1980.

  2. Aldinger KA, Samaan NA, Ibanez M, et al.: Anaplastic carcinoma of the thyroid: a review of 84 cases of spindle and giant cell carcinoma of the thyroid. Cancer 41 (6): 2267-75, 1978.

  3. Carling T, Udelsman R: Thyroid tumors. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1457-72.

  4. Shimaoka K, Schoenfeld DA, DeWys WD, et al.: A randomized trial of doxorubicin versus doxorubicin plus cisplatin in patients with advanced thyroid carcinoma. Cancer 56 (9): 2155-60, 1985.

  5. Haigh PI, Ituarte PH, Wu HS, et al.: Completely resected anaplastic thyroid carcinoma combined with adjuvant chemotherapy and irradiation is associated with prolonged survival. Cancer 91 (12): 2335-42, 2001.

  6. 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 60 (4): 1137-43, 2004.

Recurrent Thyroid Cancer

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.[1] 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.[2]

The prognosis for patients with clinically detectable recurrences is generally poor, regardless of cell type.[3] Those patients who recur with local or regional tumor detected only by I131 scan, however, have a better prognosis.[4] 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.[5] Approximately 50% of the patients operated on for recurrent tumors can be rendered free of disease with a second operation.[3] Local and regional recurrences detected by I131 scan and not clinically apparent can be treated with I131 ablation and have an excellent prognosis.[6]

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.[7] When recurrent disease does not concentrate I131, external-beam or intraoperative radiation therapy can be useful in controlling symptoms related to local tumor recurrences.[8] Systemic chemotherapy can be considered. Chemotherapy has been reported to produce occasional objective responses, usually of short duration.[4][9]

A phase II study (NCT00654238) looked at the activity of sorafenib, an orally active, multityrosine kinase inhibitor that affects tumor cell proliferation and angiogenesis, administered to 30 patients with advanced iodine-refractory thyroid cancer.[10] Among 25 assessable patients, there were 7 patients with partial responses and 16 patients with stable disease. The progression-free survival for differentiated thyroid cancer patients was 84 weeks.[10][Level of evidence: 3iiDiii] Further investigation of this approach is warranted.

Current Clinical Trials

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.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Ross DS: Long-term management of differentiated thyroid cancer. Endocrinol Metab Clin North Am 19 (3): 719-39, 1990.

  2. Mazzaferri EL, Jhiang SM: Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med 97 (5): 418-28, 1994.

  3. Goretzki PE, Simon D, Frilling A, et al.: Surgical reintervention for differentiated thyroid cancer. Br J Surg 80 (8): 1009-12, 1993.

  4. De Besi P, Busnardo B, Toso S, et al.: Combined chemotherapy with bleomycin, adriamycin, and platinum in advanced thyroid cancer. J Endocrinol Invest 14 (6): 475-80, 1991.

  5. Pak H, Gourgiotis L, Chang WI, et al.: Role of metastasectomy in the management of thyroid carcinoma: the NIH experience. J Surg Oncol 82 (1): 10-8, 2003.

  6. Coburn M, Teates D, Wanebo HJ: Recurrent thyroid cancer. Role of surgery versus radioactive iodine (I131) Ann Surg 219 (6): 587-93; discussion 593-5, 1994.

  7. Mallin WH, Elgazzar AH, Maxon HR 3rd: Imaging modalities in the follow-up of non-iodine avid thyroid carcinoma. Am J Otolaryngol 15 (6): 417-22, 1994 Nov-Dec.

  8. Vikram B, Strong EW, Shah JP, et al.: Intraoperative radiotherapy in patients with recurrent head and neck cancer. Am J Surg 150 (4): 485-7, 1985.

  9. Shimaoka K, Schoenfeld DA, DeWys WD, et al.: A randomized trial of doxorubicin versus doxorubicin plus cisplatin in patients with advanced thyroid carcinoma. Cancer 56 (9): 2155-60, 1985.

  10. Gupta-Abramson V, Troxel AB, Nellore A, et al.: Phase II trial of sorafenib in advanced thyroid cancer. J Clin Oncol 26 (29): 4714-9, 2008.


This information is provided by the National Cancer Institute.

This information was last updated on February 13, 2013.

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