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What Is Well Differentiated Thyroid Cancer

The Use Of Radioactive Iodine Post

Management of the Neck in Well Differentiated Thyroid Cancer Indications and Extent of Lateral Nec

Thyroid cells are unique in that they have the cellular mechanism to absorb iodine. The iodine is used by thyroid cells to make thyroid hormone. Rarely will other cells in the body absorb or concentrate iodine. Physicians can take advantage of this fact and give radioactive iodine to patients with thyroid cancer. There are several types of radioactive iodine, with one type being toxic to cells. Papillary cancer cells absorb iodine and therefore they can be targeted for death by giving the toxic isotope . Once again, not everybody with papillary thyroid cancer needs this therapy, but those with larger tumors, spread to lymph nodes or other areas, tumors which appear aggressive microscopically, and older patients may benefit from this therapy. This is extremely individualized and no recommendations are being made here or elsewhere on this web site…too many variables are involved. But, this is an extremely effective type of targeted therapy will little or no potential down-sides .

Radioactive iodine uptake is enhanced by high TSH levels thus patients should be off of thyroid hormone replacement and on a low iodine diet for at least two weeks prior to therapy. It is usually given 6 weeks post surgery can be repeated every 12 months if necessary .

Monitoring For Recurrence And Follow

Patients treated for thyroid cancer need lifelong monitoring and follow-up care by an interdisciplinary medical team. Specific recommendations for frequency and types of tests differ according to patient needs and thyroid cancer type and stage.

In differentiated thyroid cancer, thyroglobulin levels can serve as tumor markers to assist in monitoring. Additional considerations include support for adherence to medications including thyroid hormone replacement therapy and TSH suppression.

Key aspects of long-term care:

  • Regular physical exams to check thyroid and lymph nodes
  • Neck/thyroid ultrasound imaging
  • TSH suppression and post-thyroidectomy hormone replacement therapy , with support for medication adherence
  • Monitoring blood thyroglobulin and Tg antibodies

Recurrence of thyroid cancer can occur many years after treatment. Ongoing monitoring can help with early detection of late recurrences.

Creating Prognostic Systems For Well

  • 1Department of Otolaryngology, Walter Reed National Military Medical Center, Bethesda, MD, United States
  • 2Class of 2020, Virginia Commonwealth University School of Medicine, Richmond, VA, United States
  • 3Department of Biostatistics, The George Washington University, Washington, DC, United States
  • 4Department of Surgical Oncology, John P. Murtha Cancer Center, Walter Reed National Military Medical Center, Bethesda, MD, United States
  • 5Department of Preventive Medicine & Biostatistics, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, United States

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What Is Thyroid Cancer

The thyroid gland is located on both sides of the trachea low in the front of the neck. It secretes thyroid hormone, which controls bodily functions such as heart rate, energy level and weight. Another hormone produced by the thyroid gland is calcitonin, which helps the body control calcium balance.

Thyroid cancer occurs in both men and women from the late teens to older ages. It is most common in women between the ages of 30 and 60. Most cases of thyroid cancer occur without obvious cause or risk factors, although some families have inherited forms of thyroid cancer.

Thyroid cancers are categorized by the appearance of the tumor cells on biopsy. The majority of thyroid cancers are called well differentiated thyroid cancers, meaning the cells retain important features of normal thyroid cells when they become malignant. Well differentiated thyroid cancers can be further categorized as papillary thyroid cancer and follicular thyroid cancer.

Well differentiated thyroid cancers have an excellent prognosis, and are cured in the great majority of cases. Less common types of thyroid cancer include medullary thyroid carcinoma, poorly differentiated thyroid carcinoma and anaplastic thyroid carcinoma. These types of thyroid cancers are more challenging to manage.

What Are Symptoms Of Thyroid Cancer

Poorly differentiated thyroid carcinoma: An institutional ...

Most thyroid cancers are asymptomatic. Some can cause symptoms such as pain, difficulty swallowing, enlarged lymph nodes and voice changes. Thyroid cancer is typically diagnosed by discovery of a lump or nodule that is either felt or seen incidentally on ultrasound or another imaging study. A biopsy must be performed to confirm the diagnosis.

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What You Should Be Alert For In The History

Initial evaluation of a thyroid nodule

The history should be focused on family history of thyroid cancer and risk factors for DTC. Risk factors for differentiated thyroid malignancies include a primary relative with DTC, head and neck radiation during childhood, and extremes of age . Worrisome symptoms include rapid growth of a thyroid mass over several weeks or months. Tracheal compression or invasion by thyroid cancer can result in hoarseness of voice, dyspnea or cough, especially with exertion or in the recumbent position, or hemoptysis. Initially, esophageal compression or invasion by thyroid cancer will cause dysphagia at the level of the lower neck to solids and pills, but not to liquids. Posterior invasion by DTC may result in recurrent laryngeal nerve damage, vocal cord dysfunction, and hoarseness.

Cellular Classification Of Thyroid Cancer

In thyroid cancer, cell type is an important determinant of prognosis and treatment. The thyroid has two cell types: follicular cells and parafollicular C cells. The management of thyroid cancer depends on the cell of origin and how well the integrity of the cell type is maintained. The four main types of thyroid cancer are divided into the following two categories for clinical management:

Differentiated thyroid cancers.

  • Well-differentiated.
  • Hürthle cell carcinoma, a variant of follicular carcinoma with a poorer prognosis.
  • Poorly differentiated.
  • Parafollicular C cell thyroid cancers.

  • Medullary thyroid carcinoma.
  • Other types .

  • Lymphoma.
  • Carcinosarcoma.
  • References
  • LiVolsi VA: Pathology of thyroid disease. In: Falk SA: Thyroid Disease: Endocrinology, Surgery, Nuclear Medicine, and Radiotherapy. Lippincott-Raven, 1997, pp 127-175.
  • Kushchayeva Y, Duh QY, Kebebew E, et al.: Comparison of clinical characteristics at diagnosis and during follow-up in 118 patients with Hurthle cell or follicular thyroid cancer. Am J Surg 195 : 457-62, 2008.
  • Mills SC, Haq M, Smellie WJ, et al.: Hürthle cell carcinoma of the thyroid: Retrospective review of 62 patients treated at the Royal Marsden Hospital between 1946 and 2003. Eur J Surg Oncol 35 : 230-4, 2009.
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    The Pharmacotherapy Of Thyroid Carcinoma

    The growth of thyroid cells depends on TSH, and TSH-suppressive thyroxine administration is a cornerstone of the further care of patients with well-differentiated thyroid carcinoma after surgery and radioactive iodine therapy . The desired extent of TSH suppression depends on the risk classification . Persistent postoperative hypoparathyroidism is treated with active vitamin D3 hormone and calcium. Both treatments require regular follow-up and adjustment when indicated .

    For radioactive-iodine-resistant thyroid carcinoma, data have recently become available from two placebo-controlled phase III trials . The multitargeted tyrosine kinase inhibitors sorafenib and lenvatinib are directed against the VEGF receptor family, and lenvatinib additionally inhibits FGF receptors. No significant overall survival advantage has been demonstrated for patients taking either of these tyrosine kinase inhibitors. 64% of patients taking sorafenib had to reduce the dose from the initial value of 400 mg b.i.d. 19% had to discontinue the treatment because of side effects. The more common major side effects were:

    • hand-foot syndrome

    • weight loss

    • fatigue .

    Lenvatinib treatment had to be interrupted at least temporarily in 82% of patients, and discontinued in 14%. The more common major side effects were :

    • hypertension

    • weight loss

    • diarrhea .

    6 of the 20 deaths among patients taking lenvatinib were ascribed to the drug.

    What Is The Thyroid Cancer

    Sequencing Therapies for Differentiated Thyroid Cancer

    Thyroid cancer starts in the cells of the thyroid. The thyroid is a small, butterfly-shaped gland at the front of the neck that produces hormones for growth and metabolism.

    An estimated 8,200 new cases of thyroid cancer will be diagnosed in Canadians in 2019 and 230 will die from it. Women get it three times more often than men. Between 1997 and 2015, thyroid cancer rose 6.4% annually in men. In women, thyroid cancer rose annually by 6.5% between 2002 and 2011, but then did not change from 2011 to 2015. More frequent use of diagnostic testing may be detecting earlier stage, asymptomatic thyroid cancers more frequently than in the past.

    Thyroid cancer can be divided into four types.

    Each type behaves differently and is treated differently:

    • Papillary Carcinoma is the most common type and since this type of thyroid cancer grows slowly, if found early enough, this type can often be cured.
    • Follicular Thyroid Cancer also progresses slowly, but because the cells divide faster, it can progress more quickly than papillary carcinoma.
    • Medullary Thyroid Cancer grows faster than either papillary carcinoma or follicular thyroid cancer and usually appears in members of the same family–this type can be controlled if found early enough to prevent it spreading to the rest of the body.
    • Anaplastic thyroid cancer grows and spreads very quickly–it is the most common type of thyroid cancer found in people 60 years and older.

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    Comparing Eaccd Vs Ajcc 8th Edition

    The EACCD prognostic system TNMA based on dataset 1 can be compared with the AJCC staging system in terms of stratification and prediction. We showed earlier that the EACCD system TNMA has a significantly higher survival prediction accuracy than the AJCC staging system . Below we compare the two systems by examining how they stratify patients.

    There is a strong inter-system association between AJCC staging and EACCD grouping. Table 4 presents the distribution of patients of each AJCC stage over the 7 groups of EACCD system TNMA. Note that the upper right and lower right corners of the table are filled with 0. We see that the higher stage the patient is assigned to by the AJCC system, the higher-risk group the patient is assigned to by the EACCD, and vice versa. In fact, the assignment to ordered stages and the assignment to ordered groups have a Spearman’s rank correlation of 0.8798 with a p-value of 1.7 × 1013.

    Table 4. Contingency table between EACCD grouping and AJCC staging on the basis of T, N, M, A, and dataset 1 that contains the SEER well-differentiated thyroid cancer patients diagnosed 20042010.

    In summary, the EACCD prognostic system TNMA has a higher prognostic accuracy than the AJCC staging system in stratification of patients, EACCD grouping and AJCC staging are positively associated though each has its own advantages and disadvantages.

    Management Of Thyroid Cancer

    Malignant diagnoses require surgical intervention. Papillary thyroid carcinoma and medullary thyroid carcinoma are often positively identified on the basis of FNAB results alone. Cervical metastases discovered preoperatively or intraoperatively should be removed by means of en bloc lymphatic dissection of the respective cervical compartment while sparing the nonlymphatic structures.

    Well-differentiated neoplasms

    Patients with follicular neoplasm, as determined with FNAB results, should undergo surgery for thyroid lobectomy for tissue diagnosis. The extent of surgical therapy for well-differentiated neoplasms is controversial. Primary treatment for papillary and follicular carcinoma is surgical excision whenever possible. Total thyroidectomy has been the mainstay for treating well-differentiated thyroid carcinoma. Modifications to total thyroidectomy include subtotal thyroidectomy to reduce the risk of recurrent laryngeal nerve injury and hypoparathyroidism.

    A 2015 consensus statement from the American Thyroid Association on the management of patients with differentiated thyroid cancer who have recurrent/persistent nodal disease stated the following :

    Hürthle cell carcinomas

    Medullary thyroid carcinomas and familialmedullary thyroid carcinomas

    Anaplastic thyroid carcinoma, primary thyroid lymphoma, thyroid sarcoma

    The treatment for thyroid sarcomas is total thyroidectomy. Radiation therapy may be used in an adjunctive setting.

    Postsurgical management

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    Risks Of Thyroid Surgery

    The two most common risks of thyroid surgery include damage to the parathyroid glands or the recurrent laryngeal nerves, structures that are directly attached to the thyroid gland.

    • Parathyroid glands: There are four parathyroid glands, two attached to the back of each thyroid lobe. They are about the size of a pencil eraser or pea. The parathyroid glands control the level of calcium in the body. Damage to the parathyroid glands can affect calcium levels and cause significant health risks if left untreated.
    • Recurrent laryngeal nerve : The RLN is very thin, about the diameter of a piece of angel hair pasta. The RLN controls the vocal cords and helps protect the airway so food, liquid or other items do not enter the lungs.

    The risks of thyroid surgery can be decreased by having the operation performed by an experienced surgical team that completed at least 30 thyroid surgeries per year. The surgeons at the Pediatric Thyroid Center at CHOP perform more than 75 thyroid surgeries a year. The permanent complication rate for thyroid surgery patients at CHOP is less than 2 percent significantly lower than the national average.

    Sarcoma Of The Thyroid Gland

    GO BIG or GO HOME: Poorly Differentiated Thyroid Carcinoma (2)

    Sarcomas that arise in the thyroid gland are uncommon. They are aggressive tumors that most likely arise from stromal or vascular tissue in the gland. Malignancies that appear to be sarcomas should be differentiated from anaplastic thyroid carcinomas, which can appear sarcomatous.

    The treatment for thyroid sarcomas is total thyroidectomy. Radiation therapy may be used in an adjunctive setting. Most sarcomas are unresponsive to chemotherapy. Recurrence is common, as it is with sarcomas arising in other sites in the body, and the patient’s overall prognosis is poor.

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    Initial Risk Stratification And Management

    Initial therapy after surgery is determined by AJCC TMN staging which predicts the risk of death and the American Thyroid Association risk assessment that predicts the risk of tumor recurrence.

    Risk Stratification

    The ATA guidelines provides an Initial Risk Stratification System for DTC classifies disease into low, medium and high risk of disease recurrence or persistence. In reality, the risk of recurrence is a continuum determined by different variables. If patients receive radioactive iodine therapy, this may affect the initial staging and ATA risk assessment based on the findings of the post therapy scan.

    Risk of recurrent disease rises when the nodes is > 3 cm, the number of lymph nodes found at surgery is > 5 or if there is extrathyroidal invasion of the tumor outside the thyroid. Risk of death rises when nodes are found in the lateral neck or there is gross invasion or distant metastases .

    The most recent ATA 2015 thyroid cancer guidelines have suggested modifications to the risk stratification system based on additional variables including extent of lymph node involvement and degree of vascular invasion in follicular thyroid cancer. These modifications have yet to be validated.

    Radioiodine therapy

    Figure 1.

    Initial thyroid hormone suppression therapy and TSH goal

    Treatment Of Differentiated Thyroid Cancer

    Care by a multidisciplinary pediatric team is important to manage assessment, treatment, and long-term monitoring of patients with pediatric thyroid cancer. Care decisions are focused on balancing risk of continued disease and harm due to treatment side effects. Because of the risk of recurrence and other considerations , ongoing follow-up is needed for all patients.

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    Prognosis And Survival For Thyroid Cancer

      If you have thyroid cancer, you may have questions about your prognosis. A prognosis is the doctors best estimate of how cancer will affect someone and how it will respond to treatment. Prognosis and survival depend on many factors. Only a doctor familiar with your medical history, the type, stage and characteristics of your cancer, the treatments chosen and the response to treatment can put all of this information together with survival statistics to arrive at a prognosis.

      A prognostic factor is an aspect of the cancer or a characteristic of the person that the doctor will consider when making a prognosis. A predictive factor influences how a cancer will respond to a certain treatment. Prognostic and predictive factors are often discussed together. They both play a part in deciding on a treatment plan and a prognosis.

      The following are prognostic and predictive factors for thyroid cancer.

      Differentiated Thyroid Cancer In Patients Younger Than 55

      Management of Differentiated Thyroid Carcinoma in the Era of Targeted Therapy

      Younger people have a low likelihood of dying from differentiated thyroid cancer. The TNM stage groupings for these cancers take this fact into account. So, all people younger than 55 years with these cancers are stage I if they have no distant spread and stage II if they have distant spread. This table includes patients 55 or older as well as younger than 55.

      AJCC Stage

      Any N

      The cancer is any size and might or might not have spread to nearby lymph nodes .

      It has spread to other parts of the body, such as distant lymph nodes, internal organs, bones, etc. .

      * The following additional categories are not listed on the table above:

      • TX: Main tumor cannot be assessed due to lack of information.
      • T0: No evidence of a primary tumor. The N categories are described in the table above, except for:
      • NX: Regional lymph nodes cannot be assessed due to lack of information.

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      What About Thyroid Hormone Pills After Thyroid Cancer Surgery

      Regardless of whether a patient has just one thyroid lobe and the isthmus removed, or the entire thyroid gland removed, most experts agree they should be placed on thyroid hormone for the rest of their lives. This is to replace the hormone in those who have no thyroid left, and to suppress further growth of the gland in those with some tissue left in the neck. There is good evidence that follicular carcinoma responds to thyroid stimulating hormone secreted by the pituitary, therefore, exogenous thyroid hormone is given which results in decreased TSH levels and a lower impetus for any remaining cancer cells to grow. Recurrence and mortality rates have been shown to be lower in patients receiving suppression.

      Comparing Eaccd With Other Models

      Other efforts have been made to expand the AJCC staging system by integrating additional factors. Two major approaches are available in the literature, one based on Cox regression modeling and the other on tree modeling .

      Cox regression modeling, focuses on optimal fitting to the data, can achieve a high accuracy in survival prediction. The main downside is that no clear rule can be extracted from the output to stratify patients into risk groups analogous to AJCC stages.

      Traditional survival tree modeling, partitioning the space of values of factors into disjoint and non-overlapping regions, can be used to explicitly define prognostic groups. However, tree models in general do not provide a high prediction accuracy.

      In contrast, the EACCD approach introduced in this paper computes the survival difference between any two cohorts of patients and utilizes these differences to stratify patients, where the number of groups from stratification is determined by potentially largest C-index. Therefore, this approach takes into account both stratification and prediction.

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