Elsevier

Oral Oncology

Volume 50, Issue 6, June 2014, Pages 577-586
Oral Oncology

Review
ACR Appropriateness Criteria® thyroid carcinoma

https://doi.org/10.1016/j.oraloncology.2013.12.004Get rights and content

Summary

The ACR Head and Neck Cancer Appropriateness Criteria Committee reviewed relevant medical literature to provide guidance for those managing patients with thyroid carcinoma. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Thyroid cancer is the most common endocrine malignancy in the United States, most often presenting as a localized palpable nodule. Surgery is the mainstay of treatment for WDTC, with most patients undergoing complete resection of their disease having good outcomes. Following surgery thyroxine supplementation should begin to suppress TSH, which unchecked can stimulate residual disease and/or metastatic progression, Adjuvant treatment with radioactive iodine (RAI) using iodine-131 (131I) is frequently used for diagnostic and therapeutic purposes. The use of EBRT for thyroid cancer has not been tested in well-designed, randomized, controlled trials and should, therefore, be considered on a case-by-case basis. Chemotherapy plays a minimal role in the management of WDTC. Novel biologic agents, such as systemic therapy options, are being actively investigated, and patients with metastatic thyroid cancer that is not iodine avid should be encouraged to enroll in clinical trials exploring novel systemic agents.

Section snippets

Introduction/background

Thyroid cancer is the most common endocrine malignancy in the United States, where the annual incidence is approximately 37,000 and increasing due to the more frequent diagnosis of early well-differentiated thyroid carcinoma (WDTC) [1]. Annually, approximately 1600 people die from thyroid malignancies [2]. Women represent approximately 75% of newly diagnosed thyroid carcinoma cases. Risk factors for thyroid cancer include exposure to ionizing radiation and a family history of the disease [3],

Anatomy and physiology of the thyroid gland

The thyroid gland is a bilobed organ joined at the isthmus, which is located just inferior to the cricoid cartilage and surrounds the anterior portion of the trachea. The recurrent and superior laryngeal nerves pass near the thyroid gland on their way to the larynx. Four parathyroid glands are usually located near the thyroid gland as well.

The physiology of the thyroid gland is unique. Thyrotropin-releasing hormone, produced within the hypothalamus, signals the anterior pituitary to release

Presentation of thyroid carcinoma

A thyroid carcinoma most often presents as a localized palpable nodule, although the disease is increasingly detected as an incidental finding resulting from imaging studies conducted to evaluate other conditions. The cancer may present with lateral cervical lymphadenopathy from metastatic disease, compressive symptoms (including respiratory embarrassment and dysphagia), and hoarseness with recurrent laryngeal nerve injury. Fine needle aspiration biopsy represents the appropriate initial

Treatment of thyroid carcinoma

Surgery is the mainstay of treatment for WDTC, and the overwhelming majority of patients who undergo complete resection of their clinical disease will do well. Adjuvant treatment with radioactive iodine (RAI) using iodine-131 (131I) is frequently used for diagnostic and therapeutic purposes. MTC, arising from C cells, is characterized by the early dissemination to lymph nodes and does not concentrate iodine. Resection should include a lymphadenectomy, the extent of which remains subject to

Well-differentiated thyroid cancer – iodine avid

Indications for postoperative adjuvant RAI are: (1) tumor >1–1.5 cm; (2) patient age > 45 years; (3) capsular, vascular, or soft-tissue invasion; (4) multifocal, residual, or recurrent disease; (5) lymph node metastasis; (6) distant metastasis; and (7) intermediate or high-risk disease based on a prognostic system. RAI is usually administered 4–12 weeks after a thyroidectomy. RAI without a known residual disease can ablate the microscopic local or distant disease. The RAI dose is usually 30 mCi for

External beam radiotherapy

The use of EBRT for thyroid cancer has not been tested in well-designed, randomized, controlled trials and should, therefore, be considered on a case-by-case basis following surgery and RAI. Indications for use of EBRT postoperatively can include gross residual disease, extracapsular or extrathyroidal extension, recurrent disease or 131I failure, poor iodine avidity, multiple pathologically involved lymph nodes, HCC histology, patient age > 45 years, or high risk on prognostic systems [41]. There

Systemic therapy

Chemotherapy plays a minimal role in the management of WDTC. Doxorubicin is currently the only FDA-approved agent for noniodine avid disease [59]. Studies are now elucidating the common genetic alterations in thyroid cancer such as the BRAF gene V600E mutation [60], which may represent targets for novel biologic agents. Similarly, vascular endothelial growth factor (VEGF) is overexpressed in WDTC, which has prompted the study of small molecule tyrosine kinase inhibitors over the past few years.

Well-differentiated thyroid cancer – medullary thyroid cancer

MTC is a neuroendocrine tumor of the parafollicular C cells, which produce calcitonin. Approximately 80% of MTC cases are sporadic, although some are familial, arising from multiple endocrine neoplasia type 2 (MEN2) syndrome. The management of patients with MEN2 syndrome should include familial screening and evaluation for aprophylactic thyroidectomy. Further discussion is beyond the scope of this review. At the time of diagnosis, approximately 50% of patients with MTC have clinically

Anaplastic thyroid cancer

Patients with ATC have a uniformly poor prognosis. ATC is a locally aggressive disease process frequently involving the regional lymph nodes, perithyroidal fat, neck musculature, larynx, trachea, esophagus, and vasculature of the neck and mediastinum. Given the rapidly growing and infiltrative nature of ATC, aggressive local therapy is often recommended, although there is no randomized evidence to support this approach. Distant metastases are present in ⩽50% of newly diagnosed cases, most

Metastatic thyroid cancer

Management of metastatic thyroid cancer depends on the histologic variant. Patients with metastatic WDTC may still benefit from local control, given the ability of RAI to eradicate distant disease. Patients with tumors that do not uptake iodine have a worse prognosis. When managing patients with extracervical metastases from thyroid cancer, the goals should be to improve survival, palliate symptoms, prevent morbidity, and limit treatment-related toxicity [97]. If the tumor remains iodine-avid,

Summary

  • •

    For WDTC, surgery and often adjuvant RAI are common components of therapy.

  • •

    The role of radiotherapy is less well defined and is often decided on a case-by-case basis.

  • •

    Systemic therapeutic options, particularly with targeted therapies, are being actively investigated.

  • •

    ATCs usually require a multimodality approach, typically with concurrent chemotherapy and radiation.

Conflict of interest statement

Sue S. Yom, MD, PhD – Clinical trial support from Genentech.

References (100)

  • T.G. Urbano et al.

    Intensity Modulated Radiotherapy (IMRT) in locally advanced thyroid cancer: acute toxicity results of a phase I study

    Radiother Oncol

    (2007)
  • D.L. Schwartz et al.

    Postoperative external beam radiotherapy for differentiated thyroid cancer: outcomes and morbidity with conformal treatment

    Int J Radiat Oncol Biol Phys

    (2009)
  • S.A. Terezakis et al.

    Role of external beam radiotherapy in patients with advanced or recurrent nonanaplastic thyroid cancer: Memorial Sloan-kettering Cancer Center experience

    Int J Radiat Oncol Biol Phys

    (2009)
  • M.E. O’Connell et al.

    Results of external beam radiotherapy in differentiated thyroid carcinoma: a retrospective study from the Royal Marsden Hospital

    Eur J Cancer

    (1994)
  • W.J. Simpson et al.

    Papillary and follicular thyroid cancer: impact of treatment in 1578 patients

    Int J Radiat Oncol Biol Phys

    (1988)
  • K.C. Bible et al.

    Efficacy of pazopanib in progressive, radioiodine-refractory, metastatic differentiated thyroid cancers: results of a phase 2 consortium study

    Lancet Oncol

    (2010)
  • T.D. Nguyen et al.

    Results of postoperative radiation therapy in medullary carcinoma of the thyroid: a retrospective study by the French Federation of Cancer Institutes – the Radiotherapy Cooperative Group

    Radiother Oncol

    (1992)
  • R. De Crevoisier et al.

    Combined treatment of anaplastic thyroid carcinoma with surgery, chemotherapy, and hyperfractionated accelerated external radiotherapy

    Int J Radiat Oncol Biol Phys

    (2004)
  • C.J. Nel et al.

    Anaplastic carcinoma of the thyroid: a clinicopathologic study of 82 cases

    Mayo Clin Proc

    (1985)
  • B. McIver et al.

    Anaplastic thyroid carcinoma: a 50-year experience at a single institution

    Surgery

    (2001)
  • N. Besic et al.

    Effect of primary treatment on survival in anaplastic thyroid carcinoma

    Eur J Surg Oncol

    (2001)
  • C.S. Wong et al.

    Myelopathy following hyperfractionated accelerated radiotherapy for anaplastic thyroid carcinoma

    Radiother Oncol

    (1991)
  • G. Mitchell et al.

    Phase II evaluation of high dose accelerated radiotherapy for anaplastic thyroid carcinoma

    Radiother Oncol

    (1999)
  • L. Davies et al.

    Increasing incidence of thyroid cancer in the United States, 1973–2002

    JAMA

    (2006)
  • A. Jemal et al.

    Cancer statistics, 2009

    CA Cancer J Clin

    (2009)
  • A.B. Schneider et al.

    Long-term risks for thyroid cancer and other neoplasms after exposure to radiation

    Nat Clin Pract Endocrinol Metab

    (2005)
  • T. Pal et al.

    Increased risk for nonmedullary thyroid cancer in the first degree relatives of prevalent cases of nonmedullary thyroid cancer: a hospital-based study

    J Clin Endocrinol Metab

    (2001)
  • M. Schlumberger et al.

    Strategies of radioiodine ablation in patients with low-risk thyroid cancer

    N Engl J Med

    (2012)
  • NCCN Clinical Practice Guidelines in Oncology. Thyroid carcinoma. Version 3.2012;...
  • A. Machens et al.

    Skip metastases in thyroid cancer leaping the central lymph node compartment

    Arch Surg

    (2004)
  • E.T. Kimura et al.

    High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma

    Cancer Res

    (2003)
  • R. Elisei et al.

    Prognostic significance of somatic RET oncogene mutations in sporadic medullary thyroid cancer: a 10-year follow-up study

    J Clin Endocrinol Metab

    (2008)
  • T. Ito et al.

    Unique association of p53 mutations with undifferentiated but not with differentiated carcinomas of the thyroid gland

    Cancer Res

    (1992)
  • K.Y. Bilimoria et al.

    Extent of surgery affects survival for papillary thyroid cancer

    Ann Surg

    (2007)
  • I.D. Hay et al.

    Unilateral total lobectomy: is it sufficient surgical treatment for patients with AMES low-risk papillary thyroid carcinoma?

    Surgery

    (1998)
  • L.J. DeGroot et al.

    Natural history, treatment, and course of papillary thyroid carcinoma

    J Clin Endocrinol Metab

    (1990)
  • H.R. Harach et al.

    Occult papillary carcinoma of the thyroid. A “normal” finding in Finland. A systematic autopsy study

    Cancer

    (1985)
  • A.M. Avram et al.

    Preablation 131-I scans with SPECT/CT in postoperative thyroid cancer patients: what is the impact on staging?

    J Clin Endocrinol Metab

    (2013)
  • I.D. Hay et al.

    Ipsilateral lobectomy versus bilateral lobar resection in papillary thyroid carcinoma: a retrospective analysis of surgical outcome using a novel prognostic scoring system

    Surgery

    (1987)
  • B. Cady et al.

    An expanded view of risk-group definition in differentiated thyroid carcinoma

    Surgery

    (1988)
  • I.D. Hay et al.

    Predicting outcome in papillary thyroid carcinoma: development of a reliable prognostic scoring system in a cohort of 1779 patients surgically treated at one institution during 1940 through 1989

    Surgery

    (1993)
  • J.L. Pasieka et al.

    Addition of nuclear DNA content to the AMES risk-group classification for papillary thyroid cancer

    Surgery

    (1992)
  • C. Alevizaki et al.

    Iodine 131 treatment for differentiated thyroid carcinoma in patients with end stage renal failure: dosimetric, radiation safety, and practical considerations

    Hormones (Athens)

    (2006)
  • P.W. Grigsby et al.

    Radiation exposure from outpatient radioactive iodine (131I) therapy for thyroid carcinoma

    JAMA

    (2000)
  • A.M. Sawka et al.

    Clinical review 170: a systematic review and metaanalysis of the effectiveness of radioactive iodine remnant ablation for well-differentiated thyroid cancer

    J Clin Endocrinol Metab

    (2004)
  • I.D. Hay et al.

    Papillary thyroid carcinoma managed at the Mayo Clinic during six decades (1940–1999): temporal trends in initial therapy and long-term outcome in 2444 consecutively treated patients

    World J Surg

    (2002)
  • W. Sacks et al.

    The effectiveness of radioactive iodine for treatment of low-risk thyroid cancer: a systematic analysis of the peer-reviewed literature from 1966 to April 2008

    Thyroid

    (2010)
  • J. Jonklaas et al.

    Outcomes of patients with differentiated thyroid carcinoma following initial therapy

    Thyroid

    (2006)
  • H.R. Maxon et al.

    Radioiodine-131 therapy for well-differentiated thyroid cancer – a quantitative radiation dosimetric approach: outcome and validation in 85 patients

    J Nucl Med

    (1992)
  • U. Mallick et al.

    Ablation with low-dose radioiodine and thyrotropin alfa in thyroid cancer

    N Engl J Med

    (2012)

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