NCCN Guidelines Insights: Thyroid Carcinoma, Version 2.2018

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  • 1 Dana-Farber/Brigham and Women's Cancer Center; Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute; Vanderbilt-Ingram Cancer Center; The University of Texas MD Anderson Cancer Center; University of Washington/Seattle Cancer Care Alliance; Yale Cancer Center/Smilow Cancer Hospital; St. Jude Children's Research Hospital/The University of Tennessee Health Science Center; UCSF Helen Diller Family Comprehensive Cancer Center; Fox Chase Cancer Center; Fred & Pamela Buffett Cancer Center; University of Michigan Rogel Cancer Center; UC San Diego Moores Cancer Center; Huntsman Cancer Institute at the University of Utah; Stanford Cancer Institute; City of Hope National Medical Center; Robert H. Lurie Comprehensive Cancer Center of Northwestern University; Roswell Park Comprehensive Cancer Center; Moffitt Cancer Center; University of Colorado Cancer Center; The Ohio State University Comprehensive Cancer Center–James Cancer Hospital and Solove Research Institute; Duke Cancer Institute; Memorial Sloan Kettering Cancer Center; University of Wisconsin Carbone Cancer Center; Mayo Clinic Cancer Center; University of Alabama at Birmingham Comprehensive Cancer Center; Massachusetts General Hospital Cancer Center; and National Comprehensive Cancer Network.
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The NCCN Guidelines for Thyroid Carcinoma provide recommendations for the management of different types of thyroid carcinoma, including papillary, follicular, Hürthle cell, medullary, and anaplastic carcinomas. These NCCN Guidelines Insights summarize the panel discussion behind recent updates to the guidelines, including the expanding role of molecular testing for differentiated thyroid carcinoma, implications of the new pathologic diagnosis of noninvasive follicular thyroid neoplasm with papillary-like nuclear features, and the addition of a new targeted therapy option for BRAF V600E–mutated anaplastic thyroid carcinoma.

Provided content development and/or authorship assistance.

Please Note

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) are a statement of consensus of the authors regarding their views of currently accepted approaches to treatment. The NCCN Guidelines® Insights highlight important changes in the NCCN Guidelines® recommendations from previous versions. Colored markings in the algorithm show changes and the discussion aims to further understanding of these changes by summarizing salient portions of the panel's discussion, including the literature reviewed.

The NCCN Guidelines Insights do not represent the full NCCN Guidelines; further, the National Comprehensive Cancer Network® (NCCN®) makes no representation or warranties of any kind regarding the content, use, or application of the NCCN Guidelines and NCCN Guidelines Insights and disclaims any responsibility for their applications or use in any way.

The full and most current version of these NCCN Guidelines is available at NCCN.org.

© National Comprehensive Cancer Network, Inc. 2018, All rights reserved. The NCCN Guidelines and the illustrations herein may not be reproduced in any form without the express written permission of NCCN.

  • 1.

    Mazzaferri EL. Thyroid carcinoma: papillary and follicular. In: Mazzaferri EL, Samaan N, eds. Endocrine Tumors. Cambridge, England: Blackwell Scientific Publications; 1993:278333.

    • Search Google Scholar
    • Export Citation
  • 2.

    Hegedus L. Clinical practice. The thyroid nodule. N Engl J Med 2004;351:1764771.

  • 3.

    Cooper DS, Doherty GM, Haugen BR. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009;19:11671214.

    • Search Google Scholar
    • Export Citation
  • 4.

    Ezzat S, Sarti DA, Cain DR, Braunstein GD. Thyroid incidentalomas. Prevalence by palpation and ultrasonography. Arch Intern Med 1994;154:18381840.

    • Search Google Scholar
    • Export Citation
  • 5.

    Noone AM, Howlader N, Krapcho M, eds. SEER Cancer Statistics Review, 1975-2015, based on November 2017 SEER data submission, posted to the SEER web site, April 2018. Bethesda, MD: National Cancer Institute; 2018. Available at: https://seer.cancer.gov/csr/1975_2015/. Accessed November 20, 2018.

    • Search Google Scholar
    • Export Citation
  • 6.

    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin 2018;68:730.

  • 7.

    Amin MB, Edge SB, Greene F, eds. AJCC Cancer Staging Manual, 8th ed. New York, NY: Springer International Publishing; 2017.

  • 8.

    Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin 2011;61:212236.

    • Search Google Scholar
    • Export Citation
  • 9.

    Jemal A, Siegel R, Ward E. Cancer statistics, 2009. CA Cancer J Clin 2009;59:225249.

  • 10.

    Kaplan MM. Clinical evaluation and management of solitary thyroid nodules. In: Braverman LE, Utiger RD, eds. Werner and Ingbar's The Thyroid: A Fundamental and Clinical Text, 9th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005:9961010.

    • Search Google Scholar
    • Export Citation
  • 11.

    Layfield LJ, Cibas ES, Gharib H, Mandel SJ. Thyroid aspiration cytology: current status. CA Cancer J Clin 2009;59:99110.

  • 12.

    Yang J, Schnadig V, Logrono R, Wasserman PG. Fine-needle aspiration of thyroid nodules: a study of 4703 patients with histologic and clinical correlations. Cancer 2007;111:306315.

    • Search Google Scholar
    • Export Citation
  • 13.

    Cibas ES, Ali SZ. The 2017 Bethesda System for Reporting Thyroid Cytopathology. Thyroid 2017;27:13411346.

  • 14.

    Giordano TJ, Beaudenon-Huibregtse S, Shinde R. Molecular testing for oncogenic gene mutations in thyroid lesions: a case-control validation study in 413 postsurgical specimens. Hum Pathol 2014;45:13391347.

    • Search Google Scholar
    • Export Citation
  • 15.

    Alexander EK, Kennedy GC, Baloch ZW. Preoperative diagnosis of benign thyroid nodules with indeterminate cytology. N Engl J Med 2012;367:705715.

    • Search Google Scholar
    • Export Citation
  • 16.

    Nikiforov YE, Ohori NP, Hodak SP. Impact of mutational testing on the diagnosis and management of patients with cytologically indeterminate thyroid nodules: a prospective analysis of 1056 FNA samples. J Clin Endocrinol Metab 2011;96:33903397.

    • Search Google Scholar
    • Export Citation
  • 17.

    Ohori NP, Nikiforova MN, Schoedel KE. Contribution of molecular testing to thyroid fine-needle aspiration cytology of “follicular lesion of undetermined significance/atypia of undetermined significance”. Cancer Cytopathol 2010;118:1723.

    • Search Google Scholar
    • Export Citation
  • 18.

    Rivera M, Ricarte-Filho J, Knauf J. Molecular genotyping of papillary thyroid carcinoma follicular variant according to its histological subtypes (encapsulated vs infiltrative) reveals distinct BRAF and RAS mutation patterns. Mod Pathol 2010;23:11911200.

    • Search Google Scholar
    • Export Citation
  • 19.

    Nikiforov YE, Steward DL, Robinson-Smith TM. Molecular testing for mutations in improving the fine-needle aspiration diagnosis of thyroid nodules. J Clin Endocrinol Metab 2009;94:20922098.

    • Search Google Scholar
    • Export Citation
  • 20.

    Musholt TJ, Fottner C, Weber MM. Detection of papillary thyroid carcinoma by analysis of BRAF and RET/PTC1 mutations in fine-needle aspiration biopsies of thyroid nodules. World J Surg 2010;34:25952603.

    • Search Google Scholar
    • Export Citation
  • 21.

    Lassalle S, Hofman V, Ilie M. Clinical impact of the detection of BRAF mutations in thyroid pathology: potential usefulness as diagnostic, prognostic and theragnostic applications. Curr Med Chem 2010;17:18391850.

    • Search Google Scholar
    • Export Citation
  • 22.

    Chudova D, Wilde JI, Wang ET. Molecular classification of thyroid nodules using high-dimensionality genomic data. J Clin Endocrinol Metab 2010;95:52965304.

    • Search Google Scholar
    • Export Citation
  • 23.

    Yarchoan M, LiVolsi VA, Brose MS. BRAF mutation and thyroid cancer recurrence. J Clin Oncol 2015;33:78.

  • 24.

    Li C, Lee KC, Schneider EB, Zeiger MA. BRAF V600E mutation and its association with clinicopathological features of papillary thyroid cancer: a meta-analysis. J Clin Endocrinol Metab 2012;97:45594570.

    • Search Google Scholar
    • Export Citation
  • 25.

    Basolo F, Torregrossa L, Giannini R. Correlation between the BRAF V600E mutation and tumor invasiveness in papillary thyroid carcinomas smaller than 20 millimeters: analysis of 1060 cases. J Clin Endocrinol Metab 2010;95:41974205.

    • Search Google Scholar
    • Export Citation
  • 26.

    Liu R, Bishop J, Zhu G. Mortality risk stratification by combining BRAF V600E and TERT promoter mutations in papillary thyroid cancer: genetic duet of BRAF and TERT promoter mutations in thyroid cancer mortality [published online September 1, 2016]. JAMA Oncol. doi: 10.1001/jamaoncol.2016.3288.

    • Search Google Scholar
    • Export Citation
  • 27.

    Sadow PM, Heinrich MC, Corless CL. Absence of BRAF, NRAS, KRAS, HRAS mutations, and RET/PTC gene rearrangements distinguishes dominant nodules in Hashimoto thyroiditis from papillary thyroid carcinomas. Endocr Pathol 2010;21:7379.

    • Search Google Scholar
    • Export Citation
  • 28.

    Rodrigues HG, De Pontes AA, Adan LF. Contribution of the BRAF oncogene in the pre-operative phase of thyroid carcinoma. Oncol Lett 2013;6:191196.

    • Search Google Scholar
    • Export Citation
  • 29.

    Canadas-Garre M, Becerra-Massare P, Lopez de la Torre-Casares M. Reduction of false-negative papillary thyroid carcinomas by the routine analysis of BRAF(T1799A) mutation on fine-needle aspiration biopsy specimens: a prospective study of 814 thyroid FNAB patients. Ann Surg 2012;255:986992.

    • Search Google Scholar
    • Export Citation
  • 30.

    Lee ST, Kim SW, Ki CS. Clinical implication of highly sensitive detection of the BRAF V600E mutation in fine-needle aspirations of thyroid nodules: a comparative analysis of three molecular assays in 4585 consecutive cases in a BRAF V600E mutation-prevalent area. J Clin Endocrinol Metab 2012;97:22992306.

    • Search Google Scholar
    • Export Citation
  • 31.

    Wang CC, Friedman L, Kennedy GC. A large multicenter correlation study of thyroid nodule cytopathology and histopathology. Thyroid 2011;21:243251.

    • Search Google Scholar
    • Export Citation
  • 32.

    Albarel F, Conte-Devolx B, Oliver C. From nodule to differentiated thyroid carcinoma: contributions of molecular analysis in 2012. Ann Endocrinol (Paris) 2012;73:155164.

    • Search Google Scholar
    • Export Citation
  • 33.

    Hodak SP, Rosenthal DSAmerican Thyroid Association Clinical Affairs Committee. Information for clinicians: commercially available molecular diagnosis testing in the evaluation of thyroid nodule fine-needle aspiration specimens. Thyroid 2013;23:131134.

    • Search Google Scholar
    • Export Citation
  • 34.

    McIver B, Castro MR, Morris JC. An independent study of a gene expression classifier (Afirma) in the evaluation of cytologically indeterminate thyroid nodules. J Clin Endocrinol Metab 2014;99:40694077.

    • Search Google Scholar
    • Export Citation
  • 35.

    Celik B, Whetsell CR, Nassar A. Afirma GEC and thyroid lesions: an institutional experience. Diagn Cytopathol 2015;43:966970.

  • 36.

    Brauner E, Holmes BJ, Krane JF. Performance of the Afirma Gene Expression Classifier in Hurthle cell thyroid nodules differs from other indeterminate thyroid nodules. Thyroid 2015;25:789796.

    • Search Google Scholar
    • Export Citation
  • 37.

    Duh QY, Angell TE, Babiarz J. Development and validation of classifiers to enhance the Afirma genomic sequencing classifier performance among Hürhtle cell specimens. Presented at the 87th Annual Meeting of the American Thryoid Association; October 18–22, 2017; Victoria, BC, Canada.

    • Search Google Scholar
    • Export Citation
  • 38.

    Nikiforova MN, Mercurio S, Wald AI. Analytical performance of the ThyroSeq v3 genomic classifier for cancer diagnosis in thyroid nodules. Cancer 2018;124:16821690.

    • Search Google Scholar
    • Export Citation
  • 39.

    Sherman SI. Cytotoxic chemotherapy for differentiated thyroid carcinoma. Clin Oncol (R Coll Radiol) 2010;22:464468.

  • 40.

    Schlumberger M, Tahara M, Wirth LJ. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med 2015;372:621630.

  • 41.

    Brose MS, Worden FP, Newbold KL. Effect of age on the efficacy and safety of lenvatinib in radioiodine-refractory differentiated thyroid cancer in the phase III SELECT trial. J Clin Oncol 2017;35:26922699.

    • Search Google Scholar
    • Export Citation
  • 42.

    Brose MS, Nutting CM, Jarzab B. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial. Lancet 2014;384:319328.

    • Search Google Scholar
    • Export Citation
  • 43.

    Carr LL, Mankoff DA, Goulart BH. Phase II study of daily sunitinib in FDG-PET-positive, iodine-refractory differentiated thyroid cancer and metastatic medullary carcinoma of the thyroid with functional imaging correlation. Clin Cancer Res 2010;16:52605268.

    • Search Google Scholar
    • Export Citation
  • 44.

    Cabanillas ME, Waguespack SG, Bronstein Y. Treatment with tyrosine kinase inhibitors for patients with differentiated thyroid cancer: the M. D. Anderson experience. J Clin Endocrinol Metab 2010;95:25882595.

    • Search Google Scholar
    • Export Citation
  • 45.

    Locati LD, Licitra L, Agate L. Treatment of advanced thyroid cancer with axitinib: phase 2 study with pharmacokinetic/pharmacodynamic and quality-of-life assessments. Cancer 2014;120:26942703.

    • Search Google Scholar
    • Export Citation
  • 46.

    Cohen EE, Rosen LS, Vokes EE. Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II study. J Clin Oncol 2008;26:47084713.

    • Search Google Scholar
    • Export Citation
  • 47.

    Cohen EE, Tortorici M, Kim S. A phase II trial of axitinib in patients with various histologic subtypes of advanced thyroid cancer: long-term outcomes and pharmacokinetic/pharmacodynamic analyses. Cancer Chemother Pharmacol 2014;74:12611270.

    • Search Google Scholar
    • Export Citation
  • 48.

    Lim SM, Chang H, Yoon MJ. A multicenter, phase II trial of everolimus in locally advanced or metastatic thyroid cancer of all histologic subtypes. Ann Oncol 2013;24:30893094.

    • Search Google Scholar
    • Export Citation
  • 49.

    Leboulleux S, Bastholt L, Krause T. Vandetanib in locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 2 trial. Lancet Oncol 2012;13:897905.

    • Search Google Scholar
    • Export Citation
  • 50.

    Shah MH, De Souza J, Wirth L. Cabozantinib in patients with radioiodine-refractory differentiated thryoid cancer who progressed on prior VEGFR-targeted therapy: results of NCI- and ITOG-sponsored multicenter phase II clinical trial [abstract]. Presented at the 15th International Thyroid Congress; October 18–23, 2015; Orlando, Florida. Abstract 73.

    • Search Google Scholar
    • Export Citation
  • 51.

    Cabanillas ME, Brose MS, Holland J. A phase I study of cabozantinib (XL184) in patients with differentiated thyroid cancer. Thyroid 2014;24:15081514.

    • Search Google Scholar
    • Export Citation
  • 52.

    Bible KC, Suman VJ, Molina JR. Efficacy of pazopanib in progressive, radioiodine-refractory, metastatic differentiated thyroid cancers: results of a phase 2 consortium study. Lancet Oncol 2010;11:962972.

    • Search Google Scholar
    • Export Citation
  • 53.

    Klein Hesselink EN, Steenvoorden D, Kapiteijn E. Therapy of endocrine disease: response and toxicity of small-molecule tyrosine kinase inhibitors in patients with thyroid carcinoma: a systematic review and meta-analysis. Eur J Endocrinol 2015;172:R215225.

    • Search Google Scholar
    • Export Citation
  • 54.

    Falchook GS, Millward M, Hong D. BRAF inhibitor dabrafenib in patients with metastatic BRAF-mutant thyroid cancer. Thyroid 2015;25:7177.

  • 55.

    Rothenberg SM, McFadden DG, Palmer EL. Redifferentiation of iodine-refractory BRAF V600E-mutant metastatic papillary thyroid cancer with dabrafenib. Clin Cancer Res 2015;21:10281035.

    • Search Google Scholar
    • Export Citation
  • 56.

    Brose MS, Cabanillas ME, Cohen EE. Vemurafenib in patients with BRAF(V600E)-positive metastatic or unresectable papillary thyroid cancer refractory to radioactive iodine: a non-randomised, multicentre, open-label, phase 2 trial. Lancet Oncol 2016;17:12721282.

    • Search Google Scholar
    • Export Citation
  • 57.

    Chou A, Fraser S, Toon CW. A detailed clinicopathologic study of ALK-translocated papillary thyroid carcinoma. Am J Surg Pathol 2015;39:652659.

    • Search Google Scholar
    • Export Citation
  • 58.

    Park G, Kim TH, Lee HO. Standard immunohistochemistry efficiently screens for anaplastic lymphoma kinase rearrangements in differentiated thyroid cancer. Endocr Relat Cancer 2015;22:5563.

    • Search Google Scholar
    • Export Citation
  • 59.

    Perot G, Soubeyran I, Ribeiro A. Identification of a recurrent STRN/ALK fusion in thyroid carcinomas. PLoS One 2014;9:e87170.

  • 60.

    Kelly LM, Barila G, Liu P. Identification of the transforming STRN-ALK fusion as a potential therapeutic target in the aggressive forms of thyroid cancer. Proc Natl Acad Sci U S A 2014;111:42334238.

    • Search Google Scholar
    • Export Citation
  • 61.

    Turski ML, Vidwans SJ, Janku F. Genomically driven tumors and actionability across histologies: BRAF-mutant cancers as a paradigm. Mol Cancer Ther 2016;15:533547.

    • Search Google Scholar
    • Export Citation
  • 62.

    Shah MH, Wei L, Wirth LJ. Results of randomized phase II trial of dabrafenib versus dabrafenib plus trametinib in BRAF-mutated papillary thyroid carcinoma [abstract]. J Clin Oncol 2017;35(Suppl):Abstract 6022.

    • Search Google Scholar
    • Export Citation
  • 63.

    Patel KN. Noninvasive encapsulated follicular variant of papillary thyroid “cancer” (or not): time for a name change. JAMA Oncol 2016;2:10051006.

    • Search Google Scholar
    • Export Citation
  • 64.

    Nikiforov YE, Seethala RR, Tallini G. Nomenclature revision for encapsulated follicular variant of papillary thyroid carcinoma: a paradigm shift to reduce overtreatment of indolent tumors. JAMA Oncol 2016;2:10231029.

    • Search Google Scholar
    • Export Citation
  • 65.

    Vivero M, Kraft S, Barletta JA. Risk stratification of follicular variant of papillary thyroid carcinoma. Thyroid 2013;23:273279.

  • 66.

    Piana S, Frasoldati A, Di Felice E. Encapsulated well-differentiated follicular-patterned thyroid carcinomas do not play a significant role in the fatality rates from thyroid carcinoma. Am J Surg Pathol 2010;34:868872.

    • Search Google Scholar
    • Export Citation
  • 67.

    Liu J, Singh B, Tallini G. Follicular variant of papillary thyroid carcinoma: a clinicopathologic study of a problematic entity. Cancer 2006;107:12551264.

    • Search Google Scholar
    • Export Citation
  • 68.

    Seethala RR, Asa SL, Bullock MJ. Protocol for the Examination of Specimens From Patients With Carcinomas of the Thyroid Gland 2017. Available at: https://cap.objects.frb.io/protocols/cp-thyroid-17protocol-4000.pdf. Accessed March 22, 2018.

    • Search Google Scholar
    • Export Citation
  • 69.

    Paulson VA, Shivdasani P, Angell TE. Noninvasive follicular thyroid neoplasm with papillary-like nuclear features accounts for over half of “carcinomas” harboring RAS mutations. Thyroid 2017;27:506511.

    • Search Google Scholar
    • Export Citation
  • 70.

    Brandler TC, Liu CZ, Cho M. Does noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) have a unique molecular profile? Am J Clin Pathol 2018;150:451460.

    • Search Google Scholar
    • Export Citation
  • 71.

    Jiang XS, Harrison GP, Datto MB. Young investigator challenge: molecular testing in noninvasive follicular thyroid neoplasm with papillary-like nuclear features. Cancer Cytopathol 2016;124:893900.

    • Search Google Scholar
    • Export Citation
  • 72.

    Song SJ, LiVolsi VA, Montone K, Baloch Z. Pre-operative features of non-invasive follicular thyroid neoplasms with papillary-like nuclear features: an analysis of their cytological, Gene Expression Classifier and sonographic findings. Cytopathology 2017;28:488494.

    • Search Google Scholar
    • Export Citation
  • 73.

    Are C, Shaha AR. Anaplastic thyroid carcinoma: biology, pathogenesis, prognostic factors, and treatment approaches. Ann Surg Oncol 2006;13:453464.

    • Search Google Scholar
    • Export Citation
  • 74.

    Smallridge RC, Ain KB, Asa SL. American Thyroid Association guidelines for management of patients with anaplastic thyroid cancer. Thyroid 2012;22:11041139.

    • Search Google Scholar
    • Export Citation
  • 75.

    Nachalon Y, Stern-Shavit S, Bachar G. Aggressive palliation and survival in anaplastic thyroid carcinoma. JAMA Otolaryngol Head Neck Surg 2015;141:11281132.

    • Search Google Scholar
    • Export Citation
  • 76.

    Kunstman JW, Juhlin CC, Goh G. Characterization of the mutational landscape of anaplastic thyroid cancer via whole-exome sequencing. Hum Mol Genet 2015;24:23182329.

    • Search Google Scholar
    • Export Citation
  • 77.

    Rosove MH, Peddi PF, Glaspy JA. BRAF V600E inhibition in anaplastic thyroid cancer. N Engl J Med 2013;368:684685.

  • 78.

    Takano T, Ito Y, Hirokawa M. BRAF V600E mutation in anaplastic thyroid carcinomas and their accompanying differentiated carcinomas. Br J Cancer 2007;96:15491553.

    • Search Google Scholar
    • Export Citation
  • 79.

    Keutgen XM, Sadowski SM, Kebebew E. Management of anaplastic thyroid cancer. Gland Surg 2015;4:4451.

  • 80.

    Subbiah V, Kreitman RJ, Wainberg ZA. Dabrafenib and trametinib treatment in patients with locally advanced or metastatic BRAF V600-mutant anaplastic thyroid cancer. J Clin Oncol 2018;36:713.

    • Search Google Scholar
    • Export Citation
  • 81.

    U.S. Food & Drug Administration. FDA approves dabrafenib plus trametinib for anaplastic thyroid cancer with BRAF V600E mutation. Available at: https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm606708.htm. Accessed August 24, 2018.

    • Search Google Scholar
    • Export Citation
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