Thyroid Cancer

You can get the best treatment for thyroid cancer at Oncoexperts, Gurgaon. It is a superspeciality oncology dedicated center at Gurgaon for treatment of thyroid cancer. We have a team of thyroid surgeons, medical oncologists and radiation oncologists who have the expertise to treat all types of thyroid cancer cases in Gurgaon, India. Doctor Sunny specialises in diagnosing, managing and surgical treatment (thyroidectomy) of thyroid disorders in Gurgaon.

Thyroid cancer is the most frequently diagnosed endocrine cancer and twelfth most commonly diagnosed cancers in the United States (US). It accounts for about 3.1% of all new cancer cases and about 0.3% of all cancer-related deaths in the US. The overall incidence of thyroid cancer has been increasing during last few decades which is postulated to be the result of improved testing procedures. Thyroid cancer is 2 to 3 times more common in women and mostly occurs at an older age (45 to 54 years) with 51 years as the median age at diagnosis.

The thyroid is a butterfly-shaped endocrine gland located just below the larynx (voice box). It consists of 2 lobes that are present on either side of the trachea and are joined together by an isthmus present anterior to the trachea. Most of the thyroid is made of follicular cells that form spherical sacs enveloping a colloid and secrete thyroid hormones – thyroxine and triiodothyronine, under the influence of thyroid stimulating hormone (TSH). Thyroid hormones regulate body’s basal metabolic rate. A few parafollicular or C-cells lie between the follicular cells in the thyroid gland and secrete calcitonin. Calcitonin is a hormone that helps in maintaining appropriate calcium level in the blood. Other, less common cells in the thyroid gland include lymphocytes, fibroblasts, and adipocytes. Four parathyroid glands are present on the posterior surface of the two lobes of the thyroid gland. The parathyroid glands secrete parathormone that helps in maintaining an appropriate level of calcium, magnesium, and phosphate in the blood. 

What are the Types of Thyroid Cancer?

Thyroid cancer doctor in gurgaon: Based on the type of cells affected, level of differentiation, appearance of cells under the microscope, and disease prognosis, thyroid cancers are divided mainly into 3 types: Differentiated (including papillary, follicular and Hrthle cell), Medullary, and Anaplastic thyroid cancers. Following are some characteristic features of these types of thyroid cancers:

Differentiated Thyroid Cancers (DTC)

These cancer cells appear similar to normal thyroid cells under the microscope and arise from follicular cells. These can be further divided into following 3 subtypes:

Papillary Carcinoma

This is the most common type of thyroid cancer, representing about 80% of all cases. Papillary carcinoma tends to grow slowly and can be treated successfully in most of the cases. Some variants of papillary carcinoma include mixed papillary-follicular, columnar, tall cell, insular, and diffuse sclerosing carcinomas. These variants (except mixed papillary-follicular) are sometimes referred to as poorly differentiated carcinomas and they tend to grow and spread rapidly.

Follicular Carcinoma

This is the second most common type of thyroid cancer, representing about 10% of all cases. Prognosis of follicular carcinoma is not as good as of papillary carcinoma but they can also be treated successfully in most cases.  

Hurthle cell Carcinoma

This type of thyroid cancer is rare and is harder to recognize and treat. They have worse prognosis among all differentiated thyroid cancers.

Medullary Thyroid Carcinoma (MTC)

These cancers arise from parafollicular cells (or C-cells) and account for about 4% of all thyroid cancers. They are also referred to as neuroendocrine tumors and generally secrete calcitonin. They do not have a good prognosis as they grow and spread rapidly. They are mainly divided into following 2 subtypes:

1. a) Sporadic MTC: They accounts for about 80% of all MTCs. They are not generally inherited and mostly affect one lobe of the thyroid gland.
2. b) Familial MTC: They comprises about 20% of all MTCs and are generally inherited. They are generally bilateral or multicentric in occurrence.

Anaplastic (Undifferentiated) Thyroid Cancer

This also arises from follicular cells and is a rare form of thyroid cancer accounting for about 2% of all cases. Anaplastic cancer cells do not look like normal cells under the microscope and known as undifferentiated cells. These are the most aggressive form of thyroid cancer and are harder to treat.

How do I know if I am at risk for Thyroid Cancer?

Various epidemiological studies have indicated a number of genetic and environmental factors that can predispose to thyroid cancer. Following is a list of such risk factors:

• Female Gender: Thyroid cancer is 2 to 3 times more common in women. Reason for this gender disparity is unknown though.
• Age: As with most other cancers, older age individuals remain at higher risk of developing thyroid cancer compared to young ones.
• History Of Radiation Exposure: Individuals with a history of radiation exposure to head and neck, especially at a younger age are at increased risk of developing thyroid cancer. The risk further increases with the increase in the radiation dose.
• Dietary Iodine Intake: A diet with very high iodine content may increase the risk of papillary thyroid cancer whereas a diet deficient in iodine content may cause follicular thyroid cancer or other benign thyroid disorders like the goiter. The risk of thyroid cancer further increases in the presence of other risk factors, such as radiation exposure.
• Family History:Individual with a history of thyroid cancer in close relatives are considered to be at increased risk of developing thyroid cancer.
• Genetic Alterations: Many inherited genetic alterations have been reported to be associated with a high incidence rate of thyroid cancer, for example (e.g.), multiple endocrine neoplasia type 2 (MEN2), familial papillary thyroid cancer, familial polyposis coli, Gardner syndrome, and Cowden disease.

What are the Symptoms and Signs of Thyroid Cancer? How do I know if I have thyroid cancer or not?

Most thyroid cancers are diagnosed at an early stage. Early diagnosis of thyroid cancer is generally associated with an improved prognosis and more chances of cure. However, in some cases, thyroid cancer is found at an advanced stage when the treatment of disease becomes difficult.

Following are some common signs and symptoms of thyroid cancer that may signal thyroid cancer:

• A lump in the neck
• Pain in the neck
• Difficulty in swallowing
• Hoarseness of voice
• Swelling in the neck
• Chronic cough that does not go away with treatment

What are the Tests or Investigations to be done to confirm the diagnosis of thyroid cancer?

If an individual is suspected to have thyroid cancer due to the presence of signs and symptoms (for example, a lump in the neck), some investigations are required to confirm the diagnosis of the disease. The detailed investigations help in distinguishing between benign thyroid disease (a benign nodule, goiter, or Grave’s disease) and thyroid cancer. Further, these investigations can help in determining the extent of invasion and the spread of disease to distant body parts, which in turn helps in selecting an appropriate treatment. Following are some commonly used diagnostic tools for thyroid cancer:

Thyroid ultrasound

Thyroid Cancer surgeon in gurgaon: In this technique, a transducer is used which directs very high-frequency sound waves towards the tissue to be examined. The sound waves are reflected off the internal structures depending on their ability to reflect these waves. The reflected sound waves are collected by a special detector (fixed near the transducer) to produce a real-time image of the internal tissues on a computer screen. This helps the doctor to examine the thyroid tissue for any abnormality. This test can distinguish between fluid-filled cysts (mostly benign) and solid tumor masses (mostly cancerous). The test can reveal certain features of the cancerous nodules like micro-calcifications, irregular borders, or abnormal vascular patterns. Nearby lymph nodes (both in the lateral and the central neck) can also be studied for any sign of cancer spread with the help of this test. This technique can sometimes be used to guide a biopsy needle to collect biopsy samples from the affected area. This test does not use any ionizing radiation and is considered as safe.

Blood Tests

Blood tests are not used to diagnose thyroid cancer itself but these tests can reveal certain important information that can provide direction to the diagnostic workup of thyroid cancer. Following are commonly employed blood test for this purpose:

Thyroid Hormones (T3, T4)

Thyroid Cancer treatment in gurgaon: The level of thyroid hormones – thyroxine and tri-iodothyronine, may be utilized to assess the functioning of thyroid gland. The thyroid hormone level is usually normal in most thyroid cancers but may be elevated in case of hyperfunctioning thyroid cancer and may require further investigations.

Thyroid Stimulating Hormone (TSH)

The TSH is secreted by the anterior pituitary and its level in the blood is regulated through negative feedback mechanism by thyroid hormones. Thus, an elevated level of TSH indicates diminished thyroid functioning while a suppressed TSH level indicates hyperfunctioning thyroid (or thyroid nodule). The hyperfunctioning thyroid nodules are rarely cancerous and can be easily detected with the help of radioiodine scan. No further investigation is generally required unless a cold nodule (an area in the thyroid with lower radioactivity then surrounding) is present. Cold nodules can be cancerous and thus require further investigation.

Calcitonin

Calcitonin is a hormone secreted by C-cells of the thyroid gland. These cells give rise to MTC that is usually associated with elevated level of calcitonin. Thus, elevated calcitonin level may signal MTC and should be handled appropriately. Calcitonin level estimation may also be helpful in the assessment of the efficacy of the treatment/surgery for MTC (which generally cause calcitonin level to decrease) and the progression/recurrence of the disease in patients with MTC (indicated by increased calcitonin level after the decrease caused by the treatment). 

Thyroglobulin Level

Thyroglobulin is a protein made by thyroid cells and its level in the blood usually remains normal in most thyroid cancers. However, level of thyroglobulin can be helpful in assessing the efficacy of the treatment/surgery (that should bring down the thyroglobulin level) and the progression/recurrence of the disease in patients with DTC (if thyroglobulin level increases, which was diminished after treatment).

Carcinoembryonic antigen (CEA)

CEA is a protein (tumor marker) that is found to be elevated in many patients with thyroid cancer (especially MTC). Monitoring of CEA level can be helpful in assessing the efficacy of the treatment/surgery (that should bring down the elevated CEA level) and the progression/recurrence of the disease in MTC patients who had high CEA levels before treatment.

Radioiodine (I-131) Scan

In this test, radioiodine (I-131) is first administered to a patient. Iodine is essential for making thyroid hormones by follicular cells of the thyroid gland. Thus, radioiodine is absorbed by the thyroid follicular cells including the thyroid cancer cells (papillary, follicular, or Hürthle cell). This absorption of radioiodine occurs under the influence of TSH, and thus, a higher TSH level is usually achieved by injecting thyrotropin (recombinant TSH) to the patient before radioiodine dosing. The whole body is then scanned for the presence of radioiodine with the help of a radioactivity detector. Abnormal areas in thyroid gland with low radioactivity compared to the surrounding are known as ‘cold nodules’, while the areas with high radioactivity than surrounding are known as ‘hot nodules’. Cold nodules can be cancerous and require further investigation while hot nodules are usually benign.

This test is mostly utilized to assess the efficacy of a treatment/surgery and the spread/recurrence of the disease in patients with DTC. If cancer cells are detected on radioiodine scan after surgical removal of the thyroid gland, it indicates spread of disease and disease sensitive to radioiodine therapy.

Thyroid Biopsy

This is a confirmatory test and considered as gold standard in establishing the diagnosis of thyroid cancer. Biopsy sample(s) is generally collected from the suspected areas or cold nodules observed during the thyroid ultrasound or radioiodine scan, respectively. A fine needle aspiration (FNA) biopsy technique is generally utilized for the diagnosis of thyroid cancer. Sometimes, biopsy sample(s) from lymph nodes in the central or lateral neck region is also collected for examination. The collected biopsy samples are examined under the microscope in a laboratory and can provide very useful information such as the type of thyroid cancer, the severity of cancerous changes involved (level of differentiation), and the presence of specific defective genes or proteins in the cancer cells. 

Imaging Tests

These tests are generally employed after the establishment of the pathological diagnosis. They help to detect the spread of disease to distant body parts and assess the stage of the disease so that an appropriate treatment option can be selected. Alternatively, these tests are employed after treatment to evaluate the treatment efficacy and to detect disease response, progression, or recurrence. 

Computed tomography (CT) scan

In this technique, detailed cross-sectional images of body organs are generated using x-rays, with or without a contrast medium. It can help diagnose the spread of disease to nearby/distant lymph nodes and other organs, and may also be used to guide a biopsy needle into the affected area.

Magnetic resonance imaging (MRI) scan

This technique provides detailed images of tissues inside the body using radio waves, strong magnetic field, and gadolinium contrast. It can accurately diagnose the extent of invasion and spread of disease to nearby/distant body parts.

Positron emission tomography (PET) scan

This technique uses a radioactive substance (e.g.fluorodeoxyglucose [FDG]) that is given intravenously prior to the procedure. Cancer cells absorb larger amounts of the radioactive substance than normal cells. The areas of higher radioactivity indicate cancerous tissue on the PET scan. Thus, this technique can diagnose spread of disease to distant body parts. It is usually combined with CT scan (PET/CT).

Bone Scan

In this test, a radioactive material is injected into the vein of the patient, which gets accumulated in the areas of bones affected by the disease, which are then detected with the help of radioactivity detectors. In this way, it may help to detect the spread of cancer to bones. 

How do I know my Stage of Thyroid Cancer?

Staging helps to determine the disease prognosis, and to select an appropriate treatment strategy.  TNM is the most commonly used staging system for the thyroid cancer. The system uses mainly 3 parameters to estimate the overall stage of a disease: “T” stands for “Tumor Size”; “N” for “Lymph Nodes”; and “M” for “Metastasis”. Numbers and/or letters after T (1, 2, 3a, 3b, 4a, and 4b), N (0, 1, 1a, and 1b), and M (0 and 1) provide more details about each of these parameters. Higher the number associated with these parameters means higher the severity of the disease. Once T, N, and M are determined through different diagnostic techniques, this information is combined to assign an overall stage (from 0 to IV) to the disease.

In case of thyroid cancer, the overall disease prognosis depends on the type of cancer, and thus, different factors (apart from TNM) determine the overall stage for different types of thyroid cancer. Following tables describe the characteristics of thyroid cancers (Differentiated, Medullary, and Anaplastic) according to different stages:

Differentiated Thyroid Carcinoma

Apart from the TNM scoring, age at diagnosis is also considered for assigning an overall stage to DTCs.

Stage	Age At Diagnosis	TNM Score	Description
I	<55 Years	Any T Any N M0	Cancer of any size that might or might not has spread to nearby lymph nodes but no spread to distant body parts.
	>/=55 Years	T1-2 N0 M0	Cancer </=4 cm in size that is confined to the thyroid gland. No spread to nearby lymph nodes or distant body parts.
II	<55 Years	Any T Any N M1	Cancer of any size that might or might not has spread to nearby lymph nodes but has spread to distant body parts.
	>/=55 Years	T1-2 N1 M0	Cancer </=4 cm in size that is confined to the thyroid gland. Cancer has spread to nearby lymph nodes but has not spread to distant body parts.
		T3a-3b Any N M0	Cancer >4 cm in size that is confined to the thyroid gland or it may have invaded into the strap muscles around the thyroid gland. Cancer might or might not has spread to nearby lymph nodes but has not spread to distant body parts.
III	>/=55 Years	T4a Any N M0	Cancer of any size that has invaded into the nearby tissues of the neck like the larynx (voice box), trachea (windpipe), esophagus (food-pipe), or the recurrent laryngeal nerve.  Cancer might or might not have spread to nearby lymph nodes but has not spread to distant body parts.
IVA	>/=55 Years	T4b Any N M0	Cancer of any size that has invaded into the important nearby structures like the spine or large blood vessels. Cancer might or might not have spread to nearby lymph nodes but has not spread to distant body parts.
IVB	>/=55 Years	Any T Any N M1	Cancer of any size that might or might not have spread to nearby lymph nodes but have spread to distant body parts like distant lymph nodes, lungs, bones, etc.

Medullary Thyroid Carcinoma (MTC)

Age at diagnosis is not considered for the staging of MTCs

Stage	TNM Score	Description
I	T1-2 N0 M0	Cancer </=4 cm in size that is confined to the thyroid gland. No spread to nearby lymph nodes or distant body parts.
II	T2-3 N0 M0	Cancer </=4 cm in size that is confined to the thyroid gland or cancer >4 cm in size that has invaded into the strap muscles around the thyroid gland. No spread to nearby lymph nodes or distant body parts.
III	T1-3 N1a M0	Cancer </= 4 cm in size that is confined to the thyroid gland or cancer >4 cm in size that has invaded into the strap muscles around the thyroid gland. Cancer has spread to nearby lymph nodes in the neck region but has not spread to distant body parts.
IVA	T4a Any N M0	Cancer of any size that has invaded into the nearby tissues of the neck like the larynx (voice box), trachea (windpipe), esophagus (food-pipe), or the recurrent laryngeal nerve. Cancer might or might not has spread to nearby lymph nodes but has not spread to distant body parts.
	T1-3 N1b M0	Cancer </= 4 cm in size that is confined to the thyroid gland or cancer >4 cm in size that has invaded into the strap muscles around the thyroid gland. Cancer has spread to nearby lymph nodes in the neck (cervical or jugular nodes) but has not spread to distant body parts.
IVB	T4b Any N M0	Cancer of any size that has invaded into the important nearby structures like the spine or large blood vessels. Cancer might or might not has spread to nearby lymph nodes but has not spread to distant body parts.
IVC	Any T Any N M1	Cancer of any size that might or might not have spread to nearby lymph nodes but has spread to distant body parts like distant lymph nodes, lungs, bones, brain etc.

Anaplastic (Undifferentiated) Thyroid Cancer

Due to the aggressive nature of the anaplastic thyroid cancers, all such cancers are considered as stage IV disease. 

Stage	TNM Score	Description
IVA	T1-3a N0 M0	Cancer of any size that is confined to the thyroid gland. No spread to nearby lymph nodes or distant body parts.
IVB	T1-3a N1 M0	Cancer of any size that is confined to the thyroid gland. Cancer has spread to nearby lymph nodes in the neck region but has not spread to distant body parts.
	T3b Any N M0	Cancer >4 cm in size that has invaded into the strap muscles around the thyroid gland. Cancer might or might not has spread to nearby lymph nodes but has not spread to distant body parts.
	T4 Any N M0	Cancer of any size that has invaded into the nearby tissues of the neck like the larynx (voice box), trachea (windpipe), esophagus (food-pipe), recurrent laryngeal nerve, spine, or large blood vessels. Cancer might or might not has spread to nearby lymph nodes but has not spread to distant body parts.
IVC	Any T Any N M1	Cancer of any size that might or might not have spread to nearby lymph nodes but has spread to distant body parts like distant lymph nodes, lungs, bones, brain etc.

What is the Treatment for Thyroid Cancer? Where can I get the best treatment for Thyroid Cancer in Gurgaon?

The treatment of thyroid cancer depends on many factors including the type of thyroid cancer, the overall stage assigned to the disease with the help of the investigational tests, and patient’s overall health.

Oncoexperts is a cancer care center in Gurgaon for treatment for thyroid cancer from our team of cancer experts that include surgical oncologists, medical oncologists, and radiation oncologists who are experts in treating all types of thyroid cancer cases.

Based on the results obtained from various clinical research studies carried out so far, following are the preferred treatment approaches for different types and stages of thyroid cancer:

Differentiated Thyroid Cancer Treatment

Stage I-II DTCs

These are generally treated with surgery (lobectomy or total thyroidectomy) with or without radioiodine therapy (depending on the size of tumor and extent of invasion) as the standard treatment.

Stage III DTCs

These are generally treated with surgery (total thyroidectomy) along with radioiodine therapy (if the disease is iodine-sensitive) or external beam radiation therapy (EBRT) as the standard treatment.

Stage IV DTCs

These are sensitive to iodine are generally treated with radioiodine therapy as the standard treatment. Stage IV DTCs that are not sensitive to iodine therapy can be treated with thyroid-suppression therapy, targeted therapy, or EBRT as per physician’s discretion. Surgery and EBRT may also be employed for palliation of symptoms of advanced disease.

Medullary Thyroid Cancer Treatment

Stage I-II MTCs

These are generally treated with surgery (total thyroidectomy) with or without EBRT as the standard treatment. 

Stage III-IV MTCs

These are generally treated with surgery (total thyroidectomy) along with thyroid hormone therapy and EBRT or targeted therapy as the standard treatment. Palliative chemotherapy may also be employed for palliation of symptoms of advanced disease. Genetic testing is generally recommended in MTCs so that other family members can also be screened and treated, as appropriate.

Anaplastic Thyroid Cancer Treatment

Stage IV Anaplastic Thyroid Cancer

Anaplastic thyroid cancers are generally already widespread at the time of diagnosis. Rarely, when the disease is confined to locoregional area, surgery (total thyroidectomy) to remove the thyroid and regional lymph nodes can be performed. For extensive disease, EBRT and/or chemotherapy are generally employed as standard treatment.

Role of Surgery

Surgery is the treatment of choice for most early-stage DTCs and MRCs and some cases of anaplastic thyroid cancers that have not spread to distant body parts and can be completely removed by a surgical procedure. The main objective of surgery is to remove the primary tumor tissue along with some affected lymph nodes (if detected by imaging tests or during the procedure). Following are some commonly employed surgical procedures for the treatment of thyroid cancer:

Lobectomy

In this surgical procedure, only the affected lobe of the thyroid gland is removed (generally along with the isthmus). This surgery is usually employed for low-risk, small DTCs (<1 cm) confined to one lobe of the thyroid gland without any lymph node involvement. The advantage of this procedure is that the patient can retain one lobe of the thyroid gland and will not require thyroid hormone supplementation after surgery. Radioiodine therapy cannot be given after this surgery as most of the iodine will be absorbed by the remnants thyroid

Total Thyroidectomy

In this surgical procedure, the entire thyroid gland is removed. Some of the suspected lymph nodes may also be removed during this procedure, especially in case of medullary or anaplastic thyroid cancers. Since all of the thyroid tissue is removed, thyroid supplementation is required after this surgery. The advantage of this procedure is that radioiodine therapy can be employed for ablation of any remaining (or recurrent) disease.

Surgery for thyroid cancer may be associated with the risk of complications, such as temporary or permanent hoarseness or loss of voice, damage to the parathyroid glands leading to low blood calcium level and associated symptoms, infection, excessive bleeding, blood clots in the neck, etc.

Radioiodine (RAI) Therapy 

In this technique, therapeutic dose of radioiodine I-131 (much higher than that used for radioiodine scan) is administered to the patient. The iodine is taken up by the thyroid cancer cells (including the normal cells if any). The radiation from the iodine can destroy the thyroid cells that have concentrated the radioiodine, without much effect on the nearby healthy cells. This treatment is usually employed for destroying any remaining thyroid cells after total thyroidectomy or iodine-sensitive advanced-stage disease. The radioiodine therapy can only work in the presence of a sufficiently high level of TSH, which is achieved by administration of thyrotropin. Radioiodine therapy may be associated with side-effects like nausea, vomiting, swelling or tenderness in the neck or salivary glands, dry mouth, low sperm count in males, and irregularity in menstrual cycles in females.

Hormone Therapy

This treatment approach includes taking thyroid hormones at slightly higher dose than normal daily after surgical removal of the thyroid gland. This serves two purposes, first it provides necessary thyroid hormone supplementation for maintaining body’s normal metabolism, and secondly, it helps in reducing the growth of any remaining/recurrent thyroid cancer cells by decreasing the TSH level in blood. It can also be combined with other treatment modalities such as EBRT or chemotherapy for the treatment of some locally advanced or metastatic thyroid cancers. Side-effects of prolonged thyroid hormone therapy may include rapid or irregular heartbeat and osteoporosis. 

External Beam Radiation Therapy (EBRT)

Radiation therapy uses high-energy x-rays or other high-energy radiations which are directed to the affected area to kill cancerous cells. EBRT is generally used when radioiodine therapy cannot be used for the treatment, for example, in case of MTCs, anaplastic thyroid cancers, and iodine resistant advanced stage DTCs. Sometimes, EBRT is used as palliative therapy to relieve pain, bleeding, and obstructive symptoms associated with the advanced-stage disease.

Is there any Targeted Therapy or oral tablets available for Thyroid Cancer? 

Targeted drugs are designed to target a specific gene or protein characteristic of the thyroid cancer cells. Examples of targeted drugs that are active against different types of thyroid cancer include Sorafenib and Lenvatinib for papillary or follicular thyroid cancer; Vandetanib and Cabozantinib for medullary thyroid cancer; and Dabrafenib and trametinib for anaplastic thyroid cancer. These drugs are generally used in the treatment of advanced-stage thyroid cancers not responsive to radioiodine or thyroid hormone therapy. The side effects associated with targeted therapy vary according to the drug used. The side effects of targeted therapy are generally mild, but these can be severe in some cases.

Surgery, radioactive iodine (I-131), thyroid hormone suppressive therapy, and radiotherapy are standard treatment modalities that can be employed in most cases of thyroid cancer. However, the efficacy of these treatment modalities remains limited for patients with metastatic, progressive and/or symptomatic disease thyroid cancer. In such cases, available treatment options include observation, targeted therapy with kinase inhibitors, and traditional cytotoxic chemotherapy. The new approach based upon targeting a genetic modification characteristic of cancer cells, for example, a mutation in the BRAF, RET/PTC, and NRAS genes or other kinase enzymes that are involved in the proliferation of cancer cells, is emerging as an effective treatment modality for progressive, symptomatic thyroid cancer.

In most thyroid cancers, kinase enzymes act as important signaling intermediates that stimulate the proliferation, angiogenesis, invasion, and spread for cancer cells or inhibit cancer cells death. Many drugs targeting these signaling kinase enzymes have been studied for the treatment of advanced-stage thyroid cancer. Most of the available/tested drugs partially inhibit multiple tyrosine kinases affecting multiple signaling pathways. Newer agents are being developed that have more selective action against particular kinases, such as BRAF, mitogen-activated extracellular signal-regulated kinase (MEK), and phosphatidylinositol 3-kinase (PI3K). Currently, researchers are focusing on developing targeted drugs to treat medullary thyroid cancer (MTC), anaplastic thyroid cancer (ATC), or other aggressive thyroid cancer types because most other treatments are not very effective against these cancers.

Following is the list of various targeted drugs that are currently approved or have shown potential for the treatment of thyroid cancer:

Lenvatinib 

Lenvatinib is an orally active, small-molecule inhibitor of vascular endothelial growth factor receptor (VEGFR) 1 to 3, platelet-derived growth factor receptor (PDGFR) alpha, RET, stem cell factor receptor (KIT) and fibroblast growth factor receptor (FGFR) 1 to 4 kinases. These kinases have been implicated to promote angiogenesis, growth, and progression of thyroid cancer cells. Lenvatinib is the preferred targeted agent and has been approved by US FDA for the treatment of patients with locally recurrent or metastatic, progressive differentiated thyroid cancer (DTC [including papillary, follicular, and poorly differentiated subtypes]) that is not responding to radioactive iodine treatment. It has been reported that patients whose tumors contain a RAS mutation have significantly better clinical outcome compared to those who lack this mutation.

The most common adverse events associated with the drug include high blood pressure, fatigue, diarrhea, pain in the bones and muscles, decreased appetite, decreased weight, nausea, mouth ulcers, headache, vomiting, abdominal pain, and speech disorders.

Sorafenib 

Sorafenib is an orally active, small-molecule inhibitor of multiple kinases including VEGFR 1 to 3, PDGFR beta, KIT, RET/PTC, and less potently, BRAF. Sorafenib is considered next preferred targeted agent after lenvatinib and has been approved by the US FDA for the treatment of patients with locally recurrent or metastatic, progressive DTC that is not responding to radioactive iodine treatment. It has been reported that the presence/absence of a BRAF or RAS mutation is not predictive of clinical outcome.

Sorafenib most commonly causes adverse events like diarrhea, fatigue, infection, hair loss, hand-foot skin reaction, rash, decreased weight, decreased appetite, nausea, abdominal pain, high blood pressure, and bleeding.

Sunitinib

Sunitinib is an orally active, small-molecule inhibitor of multiple kinases including PDGFR alpha, PDGFR beta, VEGFR 1 to 3, KIT, RET/PTC subtypes 1 and 3, and others. Various clinical trials have shown the efficacy of sunitinib in the treatment of patients with MTC. Although not approved for the treatment of DTC, it can be used in the case of progressive and/or symptomatic metastatic disease when no appropriate clinical trial or preferred TKI agents are available. Common side effects of sunitinib include fatigue, diarrhea, mouth ulcers, nausea, decreased appetite, vomiting, abdominal pain, hand-foot reaction, high blood pressure, bleeding, taste changes, and low platelet counts.

Pazopanib

Pazopanib is an orally active, small-molecule inhibitor of multiple kinases including VEGFR 1 to 3, PDGFR alpha and beta, and KIT; but it does not have a significant inhibitory activity against the RET, RET/PTC, or BRAF kinases. Thus, it seems to exert its anti-thyroid cancer effect primarily via inhibiting the formation of new blood vessels. Similar to sunitinib, it can be used in the case of progressive and/or symptomatic metastatic disease when no appropriate clinical trial or preferred TKI agents are available. The most common side effects of pazopanib included fatigue, diarrhea, nausea, decreased weight, high blood pressure, decreased appetite, hair color changes, vomiting, headache, pain in bones and muscles, abdominal pain, and problem in breathing.

Vandetanib

Vandetanib is an orally active, small-molecule inhibitor of multiple kinases including VEGFR, RET/PTC, epidermal growth factor receptor (EGFR), and others. It is considered the preferred treatment option and has been approved by US FDA for patients with unresectable, locally advanced or metastatic MTC that is either symptomatic or progressive. It helps in controlling the progression of cancer; however, overall survival advantage is not yet proved in the clinical trials.

Some common side effects of vandetanib include diarrhea, rash, high blood pressure, nausea, headache, infection, decreased appetite, and abdominal pain. It can also cause serious problems with the heart rhythm that can be fatal.

Cabozantinib

Cabozantinib is an orally active, small-molecule inhibitor that targets VEGFR 1 to 3, RET/PTC, KIT, c-MET and others. Similar to vandetanib, it is considered the preferred treatment option and has been approved by US FDA for patients with unresectable, locally advanced or metastatic MTC that is either symptomatic or progressive. Cabozantinib can also be employed for the treatment of patients with radioiodine-refractory DTC who have progressed on previous anti-VEGFR therapy.

Common side effects of the drug include diarrhea, mouth sores, decreased appetite, nausea, weight loss, fatigue, high blood pressure, hair color changes, hand-foot reaction, constipation, and abdominal pain. It can also cause serious side effects, such as severe bleeding and gastrointestinal perforation/fistula.

Efatutazone

Efatutazone is an orally active agonist of peroxisome proliferator-activated (PPAR)-gamma receptor. In combination paclitaxel (chemotherapeutic drug), it could be helpful in the treatment of patients with advanced-stage ATC unresponsive to standard therapy.

Dabrafenib & Trametinib combination treatment

Dabrafenib is a BRAF kinase inhibitor and Trametinib is a mitogen-activated extracellular signal-regulated kinase (MEK)-1 and -2 inhibitor. ATCs frequently have mutations in the BRAF V600E gene and other mutations that lead to the activation of the mitogen-activated protein kinase (MAPK) and other proteins. These proteins promote cellular growth and proliferation. The combination of dabrafenib and Trametinib has been approved by US FDA for the treatment of patient with locally advanced or metastatic ATC that possess BRAF V600E mutation and for whom no other satisfactory locoregional treatment is currently available.

Common side effects of the combined treatment regimen include dry skin, rash, itching or other skin problems, sensitivity to the sunlight, headache, fever, chills, joint or muscle pain, fatigue, cough, hair loss, nausea, diarrhea, and high blood pressure. The treatment may cause serious problems like bleeding, gastrointestinal perforation, blood clots, and eye problems in some patients.

Selumetinib

Selumetinib is an orally active, small-molecule, selective inhibitor of MEK 1 and MEK 2. It has been reported to increase the radio-iodine uptake by thyroid cancer cells. Thus, it is deemed to be efficacious in the treatment of patients with radioiodine-refractory thyroid cancer. Mainly, patients with NRAS mutation positive thyroid cancer were reported to derive the benefit of selumetinib treatment. More research is currently ongoing, which mainly focus on identifying other possible radioiodine-sensitizing applications for selumetinib.

Vemurafenib

Vemurafenib is an orally active, small-molecule, selective inhibitor of BRAF serine-threonine kinase including BRAF V600E and other kinases that are involved in abnormal cellular proliferation and metastasis. It has shown some activity for the treatment of patients with progressive radioiodine-refractory BRAF V600-mutant thyroid cancer who have previously received treatment with antiangiogenic kinase inhibitors including sorafenib. Patients with any component of squamous differentiation within the primary or secondary papillary thyroid cancer lesion may confront disease progression with this drug. Thus, caution should be taken in such patients. Common adverse events of the drug included rash, itching, sensitivity to sunlight, fatigue, weight loss, taste alteration, and hair loss.

Some other drugs, such as motesanib, axitinib, bevacizumab, lenalidomide, everolimus and drugs that inhibit specific signaling pathways involving phosphatidylinositol 3-kinase (PI3K), tropomyosin receptor kinase (TRK), and anaplastic lymphoma kinase are under clinical investigation and hold potential for the treatment of advanced-stage thyroid cancer possessing specific genetic mutations. 

The introduction of multitargeted kinase inhibitors has transformed the treatment landscape of thyroid cancer and these agents are now being employed for stabilizing the progression of locally advanced or metastatic disease. However, these drugs usually have a tumoristatic effect rather than the tumoricidal, and have not yet demonstrated any improvement in the overall survival of patients with advanced disease. Also, these agents have significant side effects and are very costly, which limit their wide-spread use. The researchers studying newer agents should consider these points and come up with drugs more efficacy and safety.

Where can I find the best specialists for Thyroid Cancer treatment in Gurgaon?

Dr. Vartika Vishwani is a surgical oncologist in Gurgaon who is an expert in thyroid cancer surgeries through minimally invasive route. 

Dr. Sunny Garg is a renowned Medical Oncologist in Gurgaon with an experience of more than 10 years of treating thyroid cancer patients. He has treated thyroid cancer patients with Targeted Therapy and Personalized Cancer Treatment.

Call Or WhatsApp +91 9686813020 For Appointment.