All About Thyroid Cancer

Transcription

1 All About Thyroid Cancer What is the thyroid? The thyroid gland is located on the anterior aspect (front) of the neck. It can be felt just below the thyroid cartilage, or "Adam's apple". It is a butterfly shaped organ that stretches across the middle of the neck just below the thyroid cartilage, with its "wings" spreading towards the head, on either side of the thyroid cartilage. These "wings" are called the lobes of the thyroid, with the middle section being called the isthmus. As an endocrine gland, the thyroid gland produces, stores, and secretes the thyroid hormones thyroxine (T4) and triiodothyronine () into the bloodstream. The thyroid does this as a response to a hormone produced by the pituitary gland, called thyroid stimulating hormone, or TSH. When the thyroid gland is "turned on" by TSH, it increases its uptake of iodine, which is required to make thyroid hormone. The principal cells of the thyroid are called follicular cells and are mainly responsible for the production and secretion of thyroid hormones. Thyroid hormone plays an important role in controlling our metabolic rate. Many functions such as body temperature and heart rate are regulated by thyroid hormone. Too much thyroid hormone in your system is called hyperthyroidism, while too little is called hypothyroidism. An imbalance of thyroid hormone may cause serious problems if not properly treated. What is thyroid cancer? It is estimated that there were 62,000 new cases of thyroid cancer diagnosed in the US in This represents 3.8 % of all new cancer cases in the United States. The incidence of thyroid cancer is increasing. There are four major histopathologic types of thyroid cancer: Papillary carcinoma (including follicular variant of papillary carcinoma; represents 75-80% of thyroid cancers) Follicular carcinoma (including Hürthle cell carcinoma; represents about 15% of thyroid cancers) Medullary carcinoma (represents about 5% of thyroid cancers) Undifferentiated (anaplastic carcinoma; represents about 1% of thyroid cancers) There are other rare types of cancers that may be found in the thyroid including: lymphomas (cancer of the lymph gland cells), and metastases (cancers from other sites that have spread to the thyroid gland, such as melanoma, breast cancer, renal cell cancer, or lung cancer). Hürthle cell carcinoma, a variant of follicular thyroid cancer is addressed in a separate article. Am I at risk for thyroid cancer? Most cases of thyroid cancer are sporadic; meaning there is no obvious predisposition or risk factor for development. However, it is more common in women, occurring in a 3:1 ratio. Studies have also shown an increase of certain types of thyroid cancer in

2 geographic areas where there is a high incidence of goiters (enlarged thyroid glands) due to lack of dietary iodine. This is further supported by the decrease of thyroid cancers in these areas when individuals are given supplemental iodine. The most firmly established risk factor for the development of thyroid cancer is having had exposure to ionizing radiation to the neck area at a young age (18 years old or younger). This is supported by the high incidence of thyroid cancer seen in many populations exposed to radiation. This includes children 18 years or younger treated with radiation therapy for cancers such as Hodgkin's disease or nasopharyngeal cancer, or as part of their therapy to prevent leukemia from spreading to the brain. In addition, children who received total body irradiation in preparation for bone marrow transplantation are also at higher risk. Radiation therapy was also used in the s for benign conditions like acne, and this population has an increased risk for thyroid cancer. Children at the time of the atomic blasts at Nagasaki and Hiroshima, or of the Chernobyl nuclear plant explosion in 1986 also have a greater incidence of thyroid cancer. In fact, thyroid cancer is one of the most common cancers noted in populations exposed to large doses of radiation through accident or war. There is usually a delay of at least a few decades between exposure and the development of cancer. However the younger the patient is at the time of radiation exposure, the higher his or her risk is of developing thyroid cancer. There is also a genetic link to thyroid cancers demonstrated in both familial medullary thyroid carcinoma (FMTC) and familial non medullary thyroid cancer (FNMTC). Five to fifteen percent of thyroid cancers may be familial associated tumors. Familial medullary thyroid cancer is associated with multiple endocrine neoplasia (MEN) type 2 syndrome and familial medullary thyroid cancer. Patients with MEN type 2 may also develop other endocrine tumors in their parathyroid gland and/or adrenal tumors, called pheochromocytoma. FNMTC may present more aggressively than other thyroid tumors; often with multifocal, bilateral presentation, vascular involvement, and lymph node metastases. These tumors may also have a higher risk of recurrence and distant metastases. In order to be diagnosed with a familial type of thyroid cancer, 3 first-degree relatives must also be diagnosed with thyroid cancer. The genetic basis for this familial syndrome is not well understood. How can I prevent thyroid cancer? As most cases of thyroid cancers are sporadic and not associated with any risk factors, there is usually no method to prevent the development of thyroid cancer. Careful examination of the thyroid and consideration of screening for patients at high risk could be considered, though general prevention of thyroid cancers is not possible. In addition, it is important that the thyroid is shielded in children who undergo diagnostic X-ray procedures, such as dental X-rays. If you have a family history of thyroid cancer, be sure to notify your primary care provider. Preventive screening in families with a strong FNMTC history can be helpful in early detection and treatment. What screening tests are available? The early detection of thyroid cancers is generally through careful visual and physical examination of the neck. Palpation of the neck will detect many clinically significant thyroid cancers, which is part of a routine physical exam. In addition, the thyroid gland is included on many radiology studies performed to evaluate other organs, such as CT scans of the lungs and cervical spine. All patients suspected to have thyroid nodules, either from physical examination or from another radiology study, should have a thyroid ultrasound performed to take a picture of the thyroid. Thyroid ultrasound uses sound waves to image the thyroid gland and surrounding structures. The ultrasound appearance of the nodule can help healthcare providers determine if a fine-needle aspiration biopsy is required to further evaluate the nodule. However, there is no evidence that it is cost-effective to

3 perform ultrasounds to screen for thyroid nodules in the general population. Notably, ultrasound detects the majority of small (<1 cm) incidental thyroid cancers, which are unlikely to affect the survival of most patients. Screening for medullary thyroid cancer, such as MEN type 2, can be quite different. The present recommendation for the majority of patients with a genetic mutation associated with MEN type 2 is to undergo a prophylactic total thyroidectomy (complete removal of the thyroid) to prevent the development of a possibly aggressive medullary thyroid cancer. What are the signs of thyroid cancer? The most common presentation of thyroid cancer is an asymptomatic thyroid nodule, identified on physical exam or found incidentally on a radiologic scan. As the thyroid gland is a fairly superficial organ in the neck, a thyroid nodule could be noticed early, at which time medical attention should be sought. By no means is every thyroid nodule a thyroid cancer. In fact, 95% of thyroid nodules are benign (non-cancerous). Less commonly, thyroid cancer can present as a large mass in the neck. The large mass can be located either in the region of the thyroid, representing the primary thyroid cancer, or in a separate region of the neck, representing a spread of cancer to the lymph nodes. Thyroid tumors can also at times present as hoarseness of the voice or with symptoms of tracheal or esophageal compression, such as shortness of breath, air hunger, difficult or painful swallowing, or neck pain. How is thyroid cancer diagnosed and staged? Once a thyroid nodule is found, the next steps are designed to determine if the nodule represents a benign growth or malignant tumor. A careful physical exam should be done by a healthcare provider, with attention to the examination of the neck to evaluate for the presence of enlarged lymph nodes. Blood tests are performed to determine the function of the thyroid gland. If laboratory tests indicate an over-functioning thyroid gland, then additional tests will be performed to determine if the nodule is composed of benign thyroid tissue that is overproducing thyroid hormone. A biopsy is not usually required for benign, "functioning" nodules. A thyroid scan will help distinguish this nodule. This scan is a nuclear medicine study using radioactive iodine. Functioning thyroid tissue takes up iodine to produce normal thyroid hormones. Therefore, the small amount of radioactive iodine used to take pictures will be taken up by those areas of the thyroid that are producing thyroid hormone. Hence, a nodule composed of functioning thyroid tissue will appear "hot" in these nuclear medicine scans (i.e., concentrating the radioactive iodine). These "hot nodules" are almost always benign and often require no further work-up for malignancy. Nodules that are "cold" (i.e., do not take up much iodine) are also often benign, though can be malignant in 15-20% of cases. Therefore, these deserve more attention and further work-up. Most patients (>95%) with thyroid nodules have normal thyroid function and the nuclear medicine thyroid scan is not indicated. For these patients, the next step in investigating a nodule is a thyroid ultrasound. Ultrasound has the ability to provide additional information about a nodule, such as its composition (solid or cystic) and its appearance (hypoechoic or dark versus hyperechoic or bright), which may increase or decrease its likelihood of being cancer. In addition, ultrasound may detect more suspicious nodules that are not able to be detected on physical exam. Ultrasound may also identify abnormal lymph nodes around the thyroid gland, which could be evaluated at the same time as the thyroid nodule. Ultrasound is an extremely powerful tool in obtaining information about a thyroid nodule. If the ultrasound appearance of the thyroid nodule is suspicious for thyroid cancer, the next step in diagnosis may be a fine-needle aspiration of the nodule (FNA). This procedure is thought to be accurate, low risk and cost effective in evaluating thyroid nodules for suspected malignancy. The American Thyroid Association has published evidence-based guidelines for

4 FNA of thyroid nodules that takes into account both the patient s history for increased thyroid cancer risk (including radiation exposure and family history) and nodule size and appearance. For example, solid nodules that appear dark or hypoechoic on ultrasound that have small calcifications are more likely to be cancerous and FNA is recommended when such nodules are small (1cm), than for fluid filled nodules without these features (>2cm for FNA). Fine needle aspiration involves placing a thin needle into the nodule, and drawing up cells from it so that they can be analyzed. Usually this is done under ultrasound guidance, meaning that an ultrasound is performed at the time of the procedure to visualize the needle placement into the nodule. FNA has a diagnostic accuracy of over 98%, though it is highly dependent on the healthcare provider's expertise in performing the test and the pathologist's experience in interpreting the results. Up to 30% of FNA biopsies will return results that are inconclusive, including follicular thyroid cancer, which cannot be diagnosed by cytology alone, or an "indeterminate" result. These patients are referred for surgery, though most will end up finding out the nodule was not cancerous. Molecular-based testing is available to help determine which nodules are benign based on their genetic profile. By analyzing the samples genetic make up, doctors can identify patients who most likely have a benign nodule and therefore, can avoid surgery in these patients. If a diagnosis of thyroid cancer is made, additional pre-operative work-up will be completed to determine if there is spread of disease to local lymph nodes. In some cases, additional imaging of the neck is required by the surgeon using a CT (usually without IV contrast) or, more commonly, MRI of the neck to evaluate lymph nodes, muscle or tracheal involvement. In rare cases, evaluation for metastasis to distant areas of the body including the lungs and bones is done prior to surgery. Staging The staging of a cancer describes how much it has grown before the diagnosis is made. Staging documents the extent of disease. Cancers cause problems because they spread and can disrupt the functioning of normal organs. One way thyroid cancers can spread is by local extension to invade through the normal structures in the throat and into adjacent structures in the neck. While this is a fairly rare complication of thyroid cancers, this tumor can spread to include the trachea and esophagus. This can cause airway compromise and difficulty swallowing. Thyroid cancer spreads most commonly through the lymphatic system. The lymphatic circulation is a complete circulation system in the body (somewhat like the blood circulatory system) that drains into various lymph nodes. When cancer cells access the lymphatic system, they can travel to lymph nodes and start new sites of cancer. This is called lymphatic spread, and may denote a poorer prognosis. Thyroid cancer can commonly spread to the lymph nodes of the neck, though (especially with papillary thyroid cancer) this may not carry a worse outcome. The lymph nodes commonly involved in thyroid cancer are those found in the anterior portion (front) of the neck, called the cervical or jugular lymph node chains. They can be found in front of the large muscles on either side of the neck that contract when the head is turned from side to side. Tumor cells that spread to the jugular lymph nodes can then spread to the "supraclavicular" lymph nodes (found behind the collarbone) and to other lymph nodes in the neck. Eventually, they can spread to lymph nodes in the chest, called the mediastinal lymph nodes. At diagnosis, up to 30% of patients have evidence of thyroid cancer spread found on ultrasound examination of the neck lymph nodes before surgery. This information helps the surgeon determine the optimal surgical procedure for the patient. Thyroid cancers can also spread through the bloodstream. Cancer cells gain access to distant organs via the bloodstream and the tumors that they cause are called metastases. Cancers of the thyroid generally spread locally or to lymph nodes before spreading distantly through the bloodstream. Hence, the incidence of distant metastases is low, with less than 5% of papillary thyroid cancers showing distant spread and between 5 to 20% of follicular thyroid cancers exhibiting metastases. If spread

5 through the bloodstream does occur, the lungs and bones are the most common organs involved. The staging system used in thyroid cancer is designed to describe the extent of disease in both the thyroid itself and the neck (with spread to the lymph nodes). The staging system used to describe thyroid tumors is the "TNM system", as described by the American Joint Committee on Cancer. The TNM systems are used to describe many types of cancers. They have three components: T-describing the extent of the "primary" tumor (the tumor in the thyroid itself); N-describing the spread to the lymph nodes; M-describing the spread to other organs (i.e.-metastases). Thyroid tumors also utilize an additional staging identifier, residual tumor or "r". American Joint Committee on Cancer (AJCC) TNM Staging for Thyroid Cancer (7th ed., 2010) The TNM breakdown is quite technical, but is provided here for your reference. Your healthcare provider will use the results of the diagnostic work up to assign the TNM result. Primary Tumor- Papillary, Follicular & Medullary Thyroid Cancer (T) May be subdivided: (s) solitary tumor, (m) multifocal tumor, the largest determines T classification TX Primary tumor cannot be assessed T0 No evidence of primary tumor T1 Tumor 2 cm or less in greatest dimension and limited to thyroid T1a Tumor 1 cm or less, limited to thyroid T1b Tumor > 1cm but no more than 2 cm in greatest dimension; limited to thyroid T2 Tumor > 2 cm but no more than 4 cm in greatest dimension; limited to thyroid Tumor > 4 cm in greatest dimension; limited to thyroid OR any tumor with minimal extrathyriod extension (to stenothyroid muscle or perithyroid soft tissue) Moderately advanced disease Tumor of any size that extends beyond the thyroid capsule and invades subcutaneous soft tissues, larynx, trachea, esophagus or recurrent laryngeal nerve

6 Very advanced disease T4b Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessel Primary Tumor- Anaplastic Carcinoma; all anaplastic carcinomas are considered T4 tumors Intrathyroidal anaplastic carcinoma T4b Anaplastic carcinoma with gross extrathyroid extension Regional Lymph Nodes (N) Regional lymph nodes= central compartment, lateral cervical and upper mediastinal lymph nodes NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Regional lymph node metastasis Metastasis to level VI (pretracheal, paratracheal and prelaryngeal/delphian lymph nodes) Metastasis to unilateral, bilateral, or contralateral cervical (levels I, II, III, IV or V) or retropharyngeal or superior mediastinal lymph nodes (level VII) Distant Metastasis (M) No distant metastasis M1 Distant metastasis Residual Tumor (R) Classification of relevance to assess impact of surgery on outcomes R0 No residual tumor R1 Microscopic residual tumor R2 Macroscopic residual tumor

7 R3 Presence of residual tumor cannot be determined Stage Grouping Papillary or Follicular (differentiated; under 45 years old) Stage I Any T Any N Stage II Any T Any N M1 Papillary or Follicular (age 45 years and older) Stage I T1 N0 Stage II T2 N0 N0 Stage III T1 T2 N0 Stage IVA T1 T2 Stage IVB T4b Any N Stage IVC Any T Any N M1 Medullary Carcinoma (all age groups) Stage I T1 N0 Stage II T2 N0 N0

8 T1 Stage III T2 N0 T1 Stage IVA T2 Stage IVB T4b Any N Stage IVC Any T Any N M1 Anaplastic Carcinoma All anaplastic carcinomas are considered Stage IV Stage IVA Any N Stage IVB T4b Any N Stage IVC Any T Any N M1 Though complicated, these staging systems help providers determine the extent of the cancer, and therefore make treatment decisions regarding a patient's cancer. The stage of cancer, or extent of disease, is based on the information gathered through the various tests done (described above) as the diagnosis and work-up of the cancer is being performed. How is thyroid cancer treated? The treatment of thyroid cancer is dependent on the type (histopathology) of thyroid cancer present, however it can involve multiple types of treatment including surgery, radioactive iodine, radiation therapy, chemotherapy/targeted therapy and/or thyroid suppressive therapy. Surgery Surgery plays a central role in the treatment of thyroid cancer. The goal is removal of the tumor. There are several options for

9 surgical procedures to treat thyroid cancer including total thyroidectomy (the removal of the entire thyroid gland), near total thyroidectomy (leaving only a small remnant of thyroid tissue with parathyroid glands, which are attached to the thyroid) and lobectomy (the removal of a single lobe of the thyroid gland). If the thyroid gland is not completely removed at the first surgical procedure, the patient is always at risk for recurrence in the portion of the thyroid left behind. Secondary operations to remove the remaining portion of the thyroid gland can also be performed. However, in patients with small (<1cm) papillary thyroid cancers, a lobectomy may be appropriate. All patients suspected to have thyroid cancer should have an ultrasound to evaluate the lymph nodes in the neck for spread of the thyroid cancer. If thyroid cancer is found to have spread to these lymph nodes, the surgeon will remove the lymph nodes at the same time the thyroid is removed. However, the role of a prophylactic removal of the lymph nodes of the neck when they are not obviously involved is unclear. The lymph nodes very close to the thyroid gland are usually dissected without much difficulty and therefore should be removed. Supplemental Thyroid Hormone Therapy Depending on the pathologic staging, patients may require additional therapy after surgery. The first and simplest is the use of supplemental thyroid hormone following surgery. Patients with near total or total thyroidectomies require supplemental thyroid hormone because the thyroid gland is no longer present. But, thyroid hormone can also act as a thyroid cancer therapy. The standard of care is to give slightly more thyroid hormone than the patient would otherwise require because this has been shown to keep any remaining thyroid cancer "asleep" or inactive through a feedback system. In other words, if the body detects that there is a sufficient amount of thyroid hormone already present (through supplementation), it will not produce signals to "turn on" the thyroid to grow and produce thyroid hormone itself. This can be quite successful in keeping residual thyroid cancers dormant. Radioactive Iodine Therapy As thyroid tissue, and some thyroid cancers, preferentially take up iodine into their cells as part of normal functioning, the use of radioactive iodine, I-131, (RAI) may also be used to kill any remaining thyroid tissue (called "remnant" ablation) and potentially any thyroid cancer cells. RAI has been shown to improve the outcome of patients with higher risk disease (specifically for patients with Stage II, III, and IV disease). The iodine is taken up into the cell and the radiation within the radioactive iodine itself is released locally, delivering a lethal dose of radiation to these cells. This treatment works well because normal thyroid cells and some thyroid cancer cells preferentially absorb and retain iodine, so other tissues are rarely affected. However, for the first few days after treatment with RAI, patients emit radiation and should avoid close contact with others. Indications for RAI include tumors with high risk features, such as sizes >2 cm, invasion of the cancer through the thyroid capsule or into the soft tissues of the neck, spread to the lymph nodes or more distantly, or recurrent disease (thyroid cancer that has come back). RAI can be a very effective therapy in many cases, though some thyroid cancers do not have ability to take up iodine, rendering RAI useless. Recent research indicates the use of RAI may increase risk of the patient developing a myelodysplastic syndrome (MDS) especially within the first two years of RAI treatments. Patients and their care teams should weigh the risks of treating low risk, well differentiated thyroid cancers with RAI. The American Thyroid association guidelines for treatment do not support treatment of low risk thyroid tumors with RAI. Radiation Therapy Radiation therapy has been shown to be effective in certain subsets of patients; in particular those with aggressive types of

10 thyroid cancer, those at high risk of recurrence, or those with residual disease still present after surgery. High risk features include incomplete resection, spread outside the thyroid gland to soft tissues of the neck or to regional lymph nodes, certain histological subtypes of thyroid cancer, and those cancers that do not take up RAI. It is also used in many cases of anaplastic thyroid cancer to attempt to halt this aggressive disease. Chemotherapy/Targeted Therapy Chemotherapy has not classically been used in the treatment of thyroid cancer. However, chemotherapy drugs such as doxorubicin and cisplatin may sometimes be used in the treatment of metastatic disease, for anaplastic thyroid cancers, or disease that has progressed after RAI or radiation therapy. Several tyrosine kinase inhibitors (type of targeted therapy) can be used in the targeted treatment of certain thyroid cancers. Tyrosine kinase inhibitors work by blocking the signals that tell cells to grow and divide. These medications include sorafenib, vemurafenib, lenvatinib, cabozantinib and vandetanib. These medications have side effects such as fatigue, rash, and hypertension, but offer effective options for patients with advanced thyroid cancer. Clinical Trials There are clinical research trials for most types of cancer, and every stage of the disease. Clinical trials are designed to determine the value of specific treatments. Trials are often designed to treat a certain stage of cancer, either as the first form of treatment offered, or as an option for treatment after other treatments have failed to work. They can be used to evaluate medications or treatments to prevent cancer, detect it earlier, or help manage side effects. Clinical trials are extremely important in furthering our knowledge of this disease. It is through clinical trials that we know what we do today, and many exciting new therapies are currently being tested. Talk to your provider about participating in clinical trials in your area. You can also explore currently open clinical trials using the OncoLink Clinical Trials Matching Service. Follow up care and survivorship Survivors of thyroid cancers require lifelong monitoring and survivorship care. There are several reasons for thi,s including appropriate monitoring and dosage of thyroid replacement hormone and evaluation for residual disease or recurrence. Thyroid cancer can recur anytime, even years after initial successful treatment. The frequency and type of testing you will require depends on the type of thyroid cancer you were treated for as well as the type of treatment(s) you have received. You should report any new or recurrent symptoms to your care team immediately. These include: a new lump or swelling in the neck, problems swallowing or breathing, hoarseness, persistent sore throat or cough not associated with a cold, and neck pain/discomfort. Typically survivors require regular physical neck examinations. These are typically done every 3-6 months for the first 1-2 years after treatment and then once a year after that initial time period. You may also need periodic testing including TSH, T4, and Thyroglobulin (Tg) levels and neck ultrasound. Calcitonin and carcinoembryonic antigen (CEA) are tumor markers for medullary thyroid cancers and will be monitored regularly in these patients. For survivors with medium or high risk tumors, you may also require a RAI whole body scan or a CT/MRI or PET scan to monitor for potential metastasis or recurrent disease. Fertility may be impacted for patients who receive RAI, especially if given in high doses or multiple times. RAI can lower sperm

11 counts and decrease sperm motility, especially while the radiation is still present in the body, however rarely is this a permanent problem. For women, RAI can impact ovarian function and cause irregular periods or periods to stop. This can last for several months after the RAI treatment. Women should avoid becoming pregnant for 6-12 months after RAI. Many survivors experience challenges with managing thyroid hormone levels, which can result in hypothyroidism. Patients who have had their parathyroid glands removed during thyroid cancer treatment may also experience low calcium levels (hypocalcemia). Your healthcare team will monitor these levels and prescribe supplemental therapy as indicated. Some patients experience changes in their voice after thyroid cancer treatment. This tends to be temporary, but some patients may experience permanent changes in the tone/quality of their voice. Fear of recurrence, financial impact of cancer treatment, employment issues and coping strategies are common emotional and practical issues experienced by thyroid cancer survivors. Your healthcare team can identify resources for support and management of these practical and emotional challenges faced during and after cancer. Cancer survivorship is a relatively new focus of oncology care. With some 15 million cancer survivors in the US alone, there is a need to help patients transition from active treatment to survivorship. What happens next, how do you get back to normal, what should you know and do to live healthy going forward? A survivorship care plan can be a first step in educating yourself about navigating life after cancer and helping you communicate knowledgeably with your healthcare providers. Create a survivorship care plan today on OncoLink. Resources ThyCa: Thyroid Cancer Survivors Association Provides education and support for people with thyroid cancer as well as funds research into the disease. Light of Life Foundation A non-profit organization which provides education and support to people with thyroid cancer and the public. Endocrine Web Provides education about various endocrine conditions, including thyroid cancers. REACT Thyroid Foundation An advocacy organization dedicated to supporting research for thyroid cancer treatments. References (requires registration) Alexander, E.K. et. al. (2015) Management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer.

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