Treatment & Management of Thyroid Cancer

Thyroid Cancer may be treated with surgery, radioactive iodine, chemotherapy or newer precision cancer medicines.

Treatment & Management of Thyroid Cancer

Medically reviewed by Dr. C.H. Weaver M.D. Medical Editor 10/2018

Treatment for thyroid cancer is tailored to each individual and may include surgery, radiation, and or systemic therapy with precision cancer medicines, immunotherapy or chemotherapy. The specific treatment depends on the stage and genomic profile of the cancer.

Treatment of Thyroid Cancer by Stage

Stage I-II: Stage I-II thyroid cancers are generally confined to the thyroid, but may include multiple sites of cancer within the thyroid.

Stage III: Stage III thyroid cancer is greater than 4 cm in diameter and is limited to the thyroid or may have minimal spread outside the thyroid.

Stage III: thyroid cancer is also referred to as locally advanced disease.

Stage IV: Stage IV thyroid cancer has spread beyond the thyroid to the soft tissues of the neck, lymph nodes in the neck, or distant locations in the body.

Recurrent: Thyroid cancer that has recurred after treatment or progressed with treatment is called recurrent disease.

Surgery for Thyroid Cancer

Patients with early stage thyroid cancer are curable with surgical removal of the cancer. Surgery to remove the entire thyroid is called a total thyroidectomy. Partial removal of the thyroid is called a lobectomy. The choice of procedure depends on age of the patient and the size of the cancer.

Patients who are at a high risk of cancer recurrence are also treated with total thyroidectomy, however a total thyroidectomy is associated with a greater risk of side effects. A total thyroidectomy is a very specialized procedure and is best executed by a skilled surgeon who has performed this operation many times. The thyroid is in close proximity to the voice box and there is a risk of injuring the nerve and thus function of the voice box.[1]

Thyroid Hormone Replacement: Regardless of whether a patient has a lobectomy or has the entire thyroid gland removed, they will receive supplemental thyroid hormone for the rest of their lives. Thyroid hormone is produced by the thyroid gland and is critical for maintaining metabolism. Supplemental thyroid hormone serves two purposes: to maintain hormone levels in the absence of a functioning thyroid and to suppress further growth of the gland and thus the cancer. The pituitary gland located in the brain produces a hormone that stimulates the thyroid to grow—called thyroid-stimulating hormone (TSH). In the presence of thyroid hormone, TSH remains low and removes the stimuli to any remaining cancer cells.

Radioactive Iodine Treatment

Iodine is a natural substance that the thyroid uses to make thyroid hormone. The radioactive form of iodine is collected by the thyroid gland in the same way as non-radioactive iodine. Since the thyroid gland is the only area of the body that uses iodine, the radiation does not concentrate in any other areas of the body. The radioactive iodine that is not taken up by thyroid cells is eliminated from the body, primarily in urine. It is therefore a safe and effective way to test and treat thyroid conditions.

Research indicates that treatment with radioactive iodine improves survival for patients with thyroid cancer that has spread to nearby lymph nodes or to distant locations in the body.[2]

Systemic Therapy: Precision Cancer Medicine, Chemotherapy, and Immunotherapy

Systemic therapy is any treatment directed at destroying cancer cells throughout the body. Some patients with early stage cancer already have small amounts of cancer that have spread outside the thyroid. These cancer cells cannot be treated with surgery alone and require systemic treatment to decrease the chance of cancer recurrence. More advanced cancers that cannot be treated with surgery can only be treated with systemic therapy. Systemic therapies commonly used in the treatment of thyroid cancer include:

Chemotherapy

Chemotherapy is any treatment involving the use of drugs to kill cancer cells. Cancer chemotherapy may consist of single drugs or combinations of drugs, and can be administered through a vein, injected into a body cavity, or delivered orally in the form of a pill. Chemotherapy is different from surgery or radiation therapy in that the cancer-fighting drugs circulate in the blood to parts of the body where the cancer may have spread and can kill or eliminate cancers cells at sites great distances from the original cancer. The drugs are usually given in cycles so that a recovery period follows every treatment period.

Most chemotherapy drugs cannot tell the difference between a cancer cell and a healthy cell. Therefore, chemotherapy often affects the body’s normal tissues and organs, which can result in complications or side effects. In order to more specifically target the cancer and avoid unwanted side effects researchers are increasingly developing precision cancer medicines.

Precision Cancer Medicines

The purpose of precision cancer medicine is to define the genomic alterations in a cancers DNA that are driving that specific cancer. By exploring the reasons for this variation, researchers have begun to pave the way for more personalized cancer treatment.[3]

Not all cancer cells are alike

Cancer cells may differ from one another based on what genes have mutations. Precision cancer medicine utilizes molecular diagnostic testing, including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome. Currently this “genomic testing” is performed on a biopsy sample of the cancer.

Once a genetic abnormality is identified, a specific precision cancer medicine or targeted therapy can be developed to attack a specific mutation or other cancer-related change in the DNA programming of the cancer cells.

Precision cancer medicine uses targeted drugs and immunotherapies engineered to directly attack the cancer cells with specific abnormalities, leaving normal cells largely unharmed. Precision cancer medicines can be used both instead of and in addition to chemotherapy to improve treatment outcomes.

Precision medicines are being used for the treatment of thyroid cancer and patients should ask their doctor about whether testing is appropriate

BRAF & MEKKinase Inhibitors: The BRAF and MEK genes are known to play a role in cell growth, and mutations of these genes are common in several types of cancer. Several thyroid cancers may carry the BRAF mutation known as V600E. This mutation produces an abnormal version of the BRAF kinase that stimulates cancer growth. Another mutation known as V600K may also be present. BRAF and MEK inhibitors are precision cancer medicines that block the activity of the V600E and V600K mutations respectively.[4],[5]

  • Zelboraf®(vemurafenib) BRAF V600E kinase inhibitor
  • Tafinlar®(dabrafenib) BRAF V600E kinase inhibitor

MEK inhibitors

  • Mekinist®(trametinib) MEK V600 kinase inhibitor
  • Cotellic® (cobimetinib) MEK V600 kinase inhibitor

Combination Therapy

A combination of a BRAF (Taflinar) and a MEK (Mekinist) inhibitor appears to decrease the emergence of disease resistance that occurs in patients treated with a BRAF mutation.

The US Food and Drug Administration (FDA) has approved Tafinlar® in combination with Mekinist® for the treatment of patients with locally advanced or metastatic anaplastic thyroid cancer with BRAF V600E mutation.[1]])

Up to 44 percent of papillary thyroid cancer patients have the BRAF genetic mutation, and studies show that Tafinlar alone or combined with MeKinist are well tolerated by patients, resulting in a 50 to 54 percent response rate among the patients advanced BRAF-mutated papillary thyroid cancer.[4]

Lenvima®(lenvatinib): As an oral anti-angiogenic therapy that targets new blood vessel growth, Lenvima® can “starve” cancer of the nutrients it needs to grow. Overall 65% of refractory thyroid cancer patients experienced a partial or complete disappearance of their cancer following treatment with Lenvima®. They survive on average 18.3 months without cancer progression compared to 3.6 months for individuals not treated with Lenvima®.[5]

Cometriq (cabozantinib) Although medullary thyroid cancers only account for approximately 2-3% of all thyroid cancers they tend to have a somewhat worse prognosis than more common types of thyroid cancer. Cometriq is a precision cancer medicine – a tyrosine kinase inhibitor. It targets specific biological pathways that contribute to the growth of several types of cancer, including the receptor tyrosine kinase RET as well as MET and VEGFR2. The drug is approved for the treatment of metastatic medullary thyroid cancer.

Nexavar (sorafenib): Differentiated thyroid cancer is the most common type of thyroid cancer and can often be cured with surgery and radioactive iodine (RAI) treatment. In some cases, however, the cancer is resistant to RAI. RAI-resistant thyroid cancers have had few effective treatment options.

Nexavar is an oral medicine that works by inhibiting certain proteins that contribute to cancer growth. It has been approved for use in patients with locally recurrent or metastatic, progressive differentiated thyroid cancer that no longer responds to RAI treatment because nexavar increased progression-free survival by 41 percent compared to treatment with a placebo.[6]

Sutent (sunitinib): Sutent is a targeted therapy that is approved for the treatment of several cancers. It works by inhibiting multiple proteins in cancer cells to limit cancer cell growth and division and is active in the treatment of thyroid cancer.[7]

PD-1 Checkpoint Inhibitors

Checkpoint inhibitors are a novel precision cancer immunotherapy that helps to restore the body’s immune system in fighting cancer by releasing checkpoints that cancer uses to shut down the immune system. PD-1 and PD -L1 are proteins that inhibit certain types of immune responses, allowing cancer cells to evade an attack by the body’s immune cells. Checkpoint inhibitor drugs that block the PD-1 pathway enhance the ability of the immune system to fight cancer. By blocking the binding of the PD-L1 ligand these drugs restore an immune cells’ ability to recognize and fight the cancer cells. Checkpoint inhibitors are approved for the treatment of many cancers and are being evaluated in advanced thyroid cancer patients

  • Keytruda® (pembrolizumab)
  • Opdivo (nivolumab)
  • Imfinzi (durvalumab)
  • Tecentriq® (atezolizumab)

References

[1] Rosa Pelizzo M, Toniato A, Boschin IM, et al. Locally advanced differentiated thyroid carcinoma: a 35-year mono-institutional experience in 280 patients. *Nucl Med Commun.*2005;26(11):965-8.

[2] Podnos YD, Smith D, Wagman LD, Ellenhorn JD. Radioactive iodine offers survival improvement in patients with follicular carcinoma of the thyroid. 2005;128(6):1072-6.

[3]

[4]

[5] Schlumberger M, Makoto T, Wirth L, et al. The New England Journal of Medicine; 372:621-630 February 12, 2015.

[6] FDA approves Nexavar to treat type of thyroid cancer. [FDA News Release]. U.S. Food and Drug Administration website. Available at:

[7] Advanced Thyroid Cancer Responds to Targeted Therapy with Sunitinib [press release]. Endocrine Society website. Available at: .

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