Stage II through IV Treatment for Papillary Thyroid Cancer

If you have Stage II to IV papillary carcinoma (advanced progression of disease), your surgery will probably be near-total (sub-total) or total thyroidectomy. Some doctors also recommend modified radical neck dissection to reduce the risk that your cancer will come back (recur) in the neck area and to help figure out the stage of your cancer. If your cancer has spread to other neck lymph nodes, you are likely to receive a radical neck dissection.

• Near-total (sub-total) thyroidectomy - This is the most common type of surgery for thyroid cancer. Because papillary thyroid cancer is often located in both left and right sides of the thyroid gland (multifocal), most surgeons will remove nearly all of the thyroid gland. However, the surgeon leaves small amounts of tissue around the parathyroid glands (which produce a hormone that helps the levels of calcium and phosphorus in the body) to reduce the risk of damage to these glands.
• Total thyroidectomy - The surgeon removes the entire thyroid, and sometimes nearby lymph nodes, through an incision in the neck. In some rare cases, the surgeon also takes out other tissues in the neck that have been affected by the cancer.
• Neck dissection - The surgeon removes lymph nodes in the front and side of the neck that may contain cancer.
• Modified radical - The surgeon removes all of the lymph nodes on one side of the neck from the lower edge of the jaw to the upper edge of the collarbone. However, the surgeon does not take out sections of muscle, nerve, and the large veins in the neck.
• Radical -  The surgeon removes all of the lymph nodes on one side of the neck from the lower edge of the jaw to the upper edge of the collarbone. The surgeon also takes out sections of muscle, nerve, and the large veins in the neck.

You will probably also be treated with radioactive iodine, which can destroy cancer cells not removed by surgery and those that have spread beyond the thyroid.

• Radioactive iodine (radioiodine) - Radioiodine can destroy the rest of the thyroid gland and thyroid cancer (if the cancer takes up iodine) without affecting the rest of your body. Radioiodine is usually given as a capsule or in liquid form about 6 weeks after surgery. If you receive the usual dose, you will probably stay in the hospital for about 2 or 3 days while you are treated. If you receive a small dose, you will probably not have to stay in the hospital.

If your metastases cannot be treated successfully with radioactive iodine, you might be treated with external beam radiation therapy, which uses high-energy x-rays or other types of radiation to kill cancer cells. It is sometimes used to reduce the chance that the disease will come back (recur) in the neck.

• External beam radiation therapy (EBRT) - Radiation from a high-energy x-ray machine (linear accelerator) outside the body is focused on the cancer cells. Most people are treated with EBRT for a few minutes 5 days a week for a few weeks or months as an outpatient.

Regardless of the type of surgery you had, you will be treated with thyroid hormone after surgery. However, if your doctor plans to treat you with radioactive iodine, you might not start taking thyroid hormone until after you finish your radioactive iodine treatments. 

• Thyroid hormone replacement - These pills can give your body the natural thyroid hormone it can no longer make on its own. The thyroid hormone pills can also slow down the growth of any cancer cells that are left in your body. The generic name of the hormone is levothyroxine sodium. It is sold as Synthroid^®, Levoxyl^®, Levothroid^®, Unithroid^®, and other brand names.

This content has been reviewed and approved by Myo Thant, MD. 

Stage I Treatment for Papillary Thyroid Cancer

Surgery is the main treatment for Stage I papillary carcinoma (earliest possible stage of diagnosis). The cure rate with surgery alone is excellent.

Your surgeon might perform a lobectomy if your cancer is only in one lobe of your thyroid, the tumor is smaller than 1 centimeter (about ½ inch), and you have no signs of cancer in the lymph nodes (tiny bean-shaped organs throughout the body that help fight infections).

• Lobectomy - Lobectomy is the removal of only the affected side of the thyroid gland. If you have a papillary cancer that is smaller than 1 centimeter (about ½ inch) and there is no sign that it has spread beyond the thyroid gland, the surgeon may perform a lobectomy.

Your surgeon might perform a near-total (sub-total) thyroidectomy if your tumor is larger than 1 centimeter, it is growing outside the capsule that covers the thyroid gland, or it has spread to the lymph nodes.

• Near-total (sub-total) thyroidectomy - Because papillary thyroid cancer is often located in both left and right sides of the thyroid gland (multifocal), most surgeons will remove nearly all of the thyroid gland. However, the surgeon leaves small amounts of tissue around the parathyroid glands (which produce a hormone that helps the levels of calcium and phosphorus in the body) to reduce the risk of damage to these glands.

Some doctors recommend neck dissection in addition to lobectomy or near-total (sub-total) thyroidectomy. This treatment can reduce the risk that your cancer will come back (recur) in the neck area. It also makes it easier to figure out the stage of your cancer.  

• Modified radical neck dissection - The surgeon removes all of the lymph nodes on one side of the neck from the lower edge of the jaw to the upper edge of the collarbone.

If you had a near-total (sub-total) thyroidectomy, especially if you are older than 45 or your tumor was larger than 1 centimeter, your doctor might recommend treatment with radioactive iodine. Radioactive iodine can destroy cancer cells not removed by surgery and those that have spread beyond the thyroid. This treatment is especially useful if you have a papillary cancer that is larger than 1.5 centimeters or has spread to the neck or other parts of the body. But it is not as effective for small cancers that are only located in the thyroid gland.

• Radioactive iodine (radioiodine) - Radioiodine can destroy the rest of the thyroid gland and thyroid cancer (if the cancer takes up iodine) without affecting the rest of your body. Radioiodine is usually given as a capsule or in liquid form about 6 weeks after surgery. If you receive the usual dose, you will probably stay in the hospital for about 2 or 3 days while you are treated. If you receive a small dose, you will probably not have to stay in the hospital.

Regardless of the type of surgery you had, you will be treated with thyroid hormone after surgery. However, if your doctor plans to treat you with radioactive iodine, you might not start taking thyroid hormone until after you finish your radioactive iodine treatments.

• Thyroid hormone replacement - These pills can give your body the natural thyroid hormone it can no longer make on its own. The thyroid hormone pills can also slow down the growth of any cancer cells that are left in your body. The generic name of the hormone is levothyroxine sodium. It is sold as Synthroid^®, Levoxyl^®, Levothroid^®, Unithroid^®, and other brand names.

This content has been reviewed and approved by Myo Thant, MD. 

Well Differentiated Thyroid Cancer Follow Up

Papillary and/or Follicular thyroid cancer will recur or persist in about 25% of patients, and 80% of these recurrences will be in the neck. Recurrence occurs most commonly in the first 2 years after thyroidectomy. In papillary thyroid cancer, however, recurrence can occur up to 45 years after surgery, whereas virtually all patients with follicular and Hürthle cell cancer recur before 12 years after surgery.

• The current recommendations for postoperative follow-up of well-differentiated thyroid cancer, except for very low-risk patients, are thyroid remnant ablation and thyroid stimulating hormone (TSH) suppression. 

• Radioiodine ablation is recommended for patients with papillary thyroid cancers larger than 1.5cm, multifocal tumors, and for those with lymph node metastases. 

• Invasive follicular and Hürthle cell cancer also warrant radioiodine therapy.  

• Doctors routinely recommend the  use 30 to 50 mCi of radioiodine in low risk and 100 to 200 mCi of radioiodine in high-risk patients. 

• The initial radioiodine treatment should be performed under hormone withdrawal, or with recombinant TSH stimulation 6-8 weeks post operatively in an iodine deficient patient. 

• Patients should have a thyroid hormone levels (TSH, T3, T4, Thyroglobulin) measured as well  pregnancy test prior to 131-Iodine scanning and ablation therapy, and post-treatment imaging. 

TSH  is known to stimulate tumor growth, invasion, angiogenesis, and thyroglobulin secretion. Therefore post operatively patients are placed on thyroid hormone replacement therapy. 

• In  low-risk patients doctors maintain the serum TSH level just below the lower limit of the normal range between 0.1 and 0.4 mU/ mL. 

• In high-risk patients the dosage is adjusted to maintain a serum TSH level less than 0.1 mU/ mL, as this has been reported to improve tumor free survival. 

Adverse effects of TSH suppression may include:  

• subclinical thyrotoxicosis 
• exacerbation of angina 
• atrial fibrillation
• osteoporosis in postmenopausal women

External beam radiation and chemotherapy have a limited role in the postoperative management of well differentiated thyroid carcinoma patients. 

• External beam radiation is used infrequently in the management of thyroid cancer except as a palliative treatment for locally advanced unresectable disease, positive tumor margins, or recurrent disease after re-resection. 

• Chemotherapy has shown only minimal benefit in the treatment of well-differentiated thyroid cancer. New clinical trials have recently become available.

Follow-up is different for patients at low, intermediate, and high risk of having persistent or recurrent disease. 

• Low risk patients are defined as patients with no local or distant metastases, complete resection of tumor contained within the thyroid with no locoregional invasion, tumor without aggressive histology, and if radioiodine was given there was no uptake outside of the thyroid bed. 

• Intermediate risk patients have microscopic invasion of tumor into the peri-thyroidal soft tissue at initial surgery or tumor with aggressive histology or vascular invasion. 

• High-risk patients have macroscopic tumor invasion, incomplete tumor resection, distant metastases, or radioiodine uptake outside the thyroid bed on the post-treatment scan after thyroid remnant ablation.

The absence of persistent disease in patients that have undergone at least a total thyroidectomy and thyroid remnant ablation comprises of no clinical evidence of tumor, no imaging evidence of tumor, and undetectable serum thyroglobulin levels during TSH suppression and stimulation in the absence of interfering antibodies.

All patients with a history of well-differentiated thyroid cancer should have yearly cervical ultrasound scanning, thyroglobulin and thyroglobulin antibodies. 

• Approximately 20% of patients who are clinically disease free with serum thyroglobulin levels less than 2 ng/mL during thyroid hormone suppression will have a thyroglobulin level greater than 5 ng/mL after rhTSH or thyroid hormone withdrawal. One third of this group will have persistent disease identified on imaging studies. Therefore, a serum thyroglobulin level above 5 ng/mL after rhTSH stimulation is highly sensitive in identifying patients with persistent disease. Furthermore, the clinical significance of minimally detectable thyroglobulin levels is unclear, especially if only detected after TSH stimulation. 

• Approximately 25% of patients with thyroid cancer have antithyroglobulin antibodies making follow-up with thyroglobulin insensitive. In this group serial serum antithyroglobulin antibody measurements may serve as an imprecise surrogate marker to detect recurrence among these patients. Accurate surveillance for possible recurrence and treatment in patients thought to be free of disease is a major goal of long-term follow-up.

SOURCE: Weill Cornell Medical College

Diagnostic Testing for Thyroid Cancer Basics

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

• 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.

• 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.

• Radioactive iodine scan (RAI scan): A procedure to find areas in the body where thyroid cancer cells may be dividing quickly. Radioactive iodine (RAI) is used because only thyroid cells take up iodine. A very small amount of RAI is swallowed, travels through the blood, and collects in thyroid tissue and thyroid cancer cells anywhere in the body. Abnormal thyroid cells take up less iodine than normal thyroid tissue. Areas that do not absorb the iodine normally (cold spots) show up lighter in the picture made by the scan. Cold spots can be either benign (not cancer) or malignant, so a biopsy is done to find out if they are cancer.

• 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.

• MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI).

• PET scan (positron emission tomography scan): A procedure to find malignant tumor cells in the body. A small amount of radioactive glucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do.

• 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.

MEDICAL REVIEW: 02/12/2012

What Causes Thyroid Cancer ?

 Although scientists have found that thyroid cancer is linked with a number of other conditions (described in  "What are the risk factors for thyroid cancer?"), the exact cause of most thyroid cancers is not yet known. Researchers have made great progress in understanding how certain changes in a person's DNA can cause thyroid cells to become cancerous. 

• DNA is the chemical in each of our cells that makes up our genes – the instructions for how our cells function. We usually look like our parents because they are the source of our DNA. However, DNA affects more than how we look. It also can influence our risk for developing certain diseases, including some kinds of cancer.

• Some genes contain instructions for controlling when our cells grow and divide. Certain genes that speed up cell division or cause cells to live longer than they should are called oncogenes. Others that slow down cell division or cause cells to die at the appropriate time are called tumor suppressor genes. Cancers can be caused by DNA changes that turn on oncogenes or turn off tumor suppressor genes.

• People inherit 2 copies of each gene – one from each parent. People can inherit damaged DNA from one or both parents, which accounts for inherited cancers. Most cancers, though, are not inherited. In these cases, a person's DNA is damaged by exposure to something in the environment, like smoking or radiation. Other DNA changes may just be random events that sometimes happen inside a cell, without having an external cause.

Papillary Thyroid Cancer:  Several DNA mutations have been found in some forms of papillary thyroid cancer. Many of these cancers have changes in specific parts of the RET gene. The altered form of this gene, known as the PTC oncogene, is found in about 10% to 30% of papillary thyroid cancers overall, and in a larger percentage of these cancers found in children and/or linked with radiation exposure. These RET mutations usually are acquired during a person's lifetime rather than being inherited. They are present only in cancer cells and are not passed on to the patient's children.

• Many (30% to 70%) papillary thyroid cancers contain a mutation of the BRAF gene. The BRAF mutation is less common in thyroid cancers in children and in those thought to arise from exposure to radiation. Cancers with BRAF changes tend to have more aggressive growth and a greater likelihood of spreading to other parts of the body. 

• Both BRAF and RET/PTC changes are thought to cause cells to grow and divide. It is extremely rare for papillary cancers to have changes in both the BRAF and RET/PTC genes. Some doctors now advise testing papillary cancer samples for these gene mutations, as some studies have suggested they may affect a person's prognosis (outlook). 

• Changes to other genes have also been tied to papillary thyroid cancer, including those in the NTRK1 gene and the METgene.

Follicular Thyroid Cancer:  Acquired changes in the RAS oncogene have a role in causing some follicular thyroid cancers.

Anaplastic Thyroid Cancer:  These cancers tend to have some of the mutations described above and often have changes in the p53 tumor suppressor gene and the CTNNB1 oncogene as well.

Medullary Thyroid Cancer:  People who have medullary thyroid carcinoma (MTC) have mutations in different parts of the RET gene compared with papillary carcinoma patients. Nearly all patients with the inherited form of MTC and about 1 of every 10 with the sporadic (non-inherited) form of MTC have a mutation in the RET gene.

• Most patients with sporadic MTC have acquired mutations present only in their cancer cells. Those with familial MTC and MEN 2 inherit the RET mutation from a parent. These mutations are present in every cell of the patient's body and can be detected by testing the DNA of blood cells.

• In people with inherited mutations of RET, one RET gene is usually normal and one is mutated. Because every person has 2RET genes but passes only one of them to a child (the child's other RET gene comes from the other parent), the odds that a person with familial MTC will pass a mutated gene on to a child are 1 in 2 (or 50%).

Last Medical Review: 06/29/2011

Last Revised: 01/20/2012

Less Recurrences for Thyroid Cancer Patients with Lymphocytic Infiltration

According to the results of a study reported at the 14th International Thyroid Congress, patients with thyroid cancer who show lymphocytic infiltration - a benign cluster of lymph cells - are more likely to have a favorable outcome.

The effect of coexistent lymphocyte infiltration (LI) on the prognosis of thyroid cancer remains controversial, as widespread lymphocyte infiltration is frequently seen in Hashimoto's thyroiditis, an inflammatory thyroid disease.

A retrospective study of 157 patients with thyroid cancer - which included papillary and follicular thyroid cancers - was conducted with all patients undergoing total or near-total thyroidectomy followed by radioiodine therapy.

The diagnosis of LI was made based on a review of the pathology reports on each patient. LI was classified according to diffuse, peritumoral - in or around the tumor - or absent.  A total of 93 patients had diffuse LI, 25 had peritumoral LI and 39 had no signs. The rate of tumor recurrence overall was 47 percent, which was lower in patients with peritumoral LI.

"Although the role of the inflammatory immune cells is complex and not well understood, our data indicates that peritumoral LI cells influence tumor behavior, as these tumors [have] lower aggressive characteristics and recurrences," wrote Dr Villagelin of the Pontifica Catholic University Campinas in São Paulo, Brazil.

 

SOURCE: endocrineweb