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New Approaches in the Management of Thyroid Cancer

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Clinical Applications of Nuclear Medicine Targeted Therapy

Abstract

With 98.1% 5-year survival rate, differentiated thyroid carcinoma is one of the best in prognosis among all cancers. The primary treatment of thyroid cancer is the surgical removal of thyroid, in most of the cases total thyroidectomy, which is followed by iodine-131 ablation therapy. Last years’ new trends apply in small thyroid carcinomas: Hemithyroidectomy is suggested, and even in cases of total thyroidectomy iodine-131 therapy should not be used. In localized thyroid carcinoma, the 5-year survival rate is more than 99% This is the main reason of choosing lobectomy and for not using the iodine-131 therapy for thyroid cancers less than 1 cm. Nevertheless, the 5-year relative survival rate in patient with distant metastasis is 55.3%. Approximately 1.2% of men and women in the USA will be diagnosed with thyroid cancer at some point during their lifetime, based on 2011–2013 data. The estimated new cases in the USA for 2017 are 56,870 individuals. Out of them about 2275 (4%) will have distant metastasis. From them about 1150 will not survive until 2022. Even though we do not have exact numbers, the same situation should be in Europe. In other parts of the world, given the situation that the diagnosis comes later, the numbers of metastatic patients should be in a higher percent. These numbers are a challenge in the management of thyroid cancer, and the progress is not impressive. The scope of the chapter is to show how these difficult cases should be managed starting on the possibility to recognize the people who will develop thyroid cancer, the initial surgical treatment of the disease, and if any progress in diagnosis and therapy has been made in the last years. The questions that we will try to answer in the next paragraphs are the following: Is there any possibility to find out the patients that will develop thyroid cancer? Can the details of the histopathology reports add information about the patient at risk to improve their management? Is the initial surgery a predictive factor in the prognosis of each patient and how this could be improved? Are the new methods of surgery adding in value regarding the managements of thyroid cancer patient? How and when surgery should be used in relapses of thyroid cancer? Localization of distant metastasis is very important. What is the role of PET/CT? What is the role of systemic therapy in treating metastatic thyroid cancer? Is there any role of external beam radiation in the management of thyroid cancer?

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References

  1. Howlader N, Noone AM, Krapcho M, Miller D, Bishop K, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA, editors. SEER cancer statistics review, 1975–2013. [Online]; 2015 [cited 2017 March 31]. Available from: http://seer.cancer.gov/csr/1975_2013/.

  2. www.cancer.org. [Online]; 2017 [cited 2017 March 31]. Available from: www.cancer.org/cancer/thyroidcancer/detailedguide/thyroid-cancer-key-statistics.

  3. Kilfoy BA, Zheng T, Holford TR, et al. International patterns and trends in thyroid cancer incidence, 1973–2002. Cancer Causes Control. 2009;20(5):525–31.

    Article  PubMed  Google Scholar 

  4. World Health Organization. International Agency for Research on Cancer. Globocan 2012: estimated cancer incidence, mortality and prevalence worldwide in 2012. Available at: http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx. Accessed 7 Feb 2016.

  5. Hall SF, Irish J, Groome P, Griffiths R. Access, excess, and overdiagnosis: the case for thyroid cancer. Cancer Med. 2014;3(1):154–61.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Ermak G, Figge JJ, Kartel NA, Davies KJ. Genetic aberrations in Chernobyl-related thyroid cancers: implications for possible future nuclear accidents or nuclear attacks. IUBMB Life. 2003;55(12):637–41.

    Article  CAS  PubMed  Google Scholar 

  7. Giannoula E, Iakovou I, Chatzipavlidou V. Risk factors and the progression of thyroid malignancies. Hell J Nucl Med. 2015;18(3):275–84.

    PubMed  Google Scholar 

  8. Leux C, Guénel P. Risk factors of thyroid tumors: role of environmental and occupational exposures to chemical pollutants. Rev Epidemiol Sante Publique. 2010;58(5):359–67.

    Article  CAS  PubMed  Google Scholar 

  9. Shah DJ, Sachs RK, Wilson DJ. Radiation-induced cancer: a modern view. Br J Radiol. 2012;85:e166–e73.

    Article  Google Scholar 

  10. Gaussen A, Legal JD, Beron-Gaillard N, et al. Radiosensitivity of human normal and tumoral thyroid cells using fluorescence in situ hybridization and clonogenic survival assay. Int J Radiat Oncol Biol Phys. 1999;44(3):683–91.

    Article  CAS  PubMed  Google Scholar 

  11. Ivanov VK, Kashcheev VV, Chekin SY, et al. Radiation-epidemiological studies of thyroid cancer incidence in Russia after the Chernobyl accident (estimation of radiation risks, 1991–2008 follow-up period). Radiat Prot Dosim. 2012;151(3):489–99.

    Article  CAS  Google Scholar 

  12. Moysich KB, Menezes RJ, Michalek AM. Chernobyl-related ionising radiation exposure and cancer risk: an epidemiological review. Lancet Oncol. 2002;3(5):269–79.

    Article  PubMed  Google Scholar 

  13. Rashed-Nizam QM, Rahman MM, Kamal M, Chowdhury MI. Assessment of radionuclides in the soil of residential areas of the Chittagong metropolitan city, Bangladesh and evaluation of associated radiological risk. J Radiat Res. 2015;56(1):22–9.

    Article  CAS  PubMed  Google Scholar 

  14. Taylor DM, Taylor SK. Environmental uranium and human health. Rev Environ Health. 1997;12(3):147–57.

    Article  CAS  PubMed  Google Scholar 

  15. Mettler FA Jr, Bhargavan M, Thomadsen BR, et al. Nuclear medicine exposure in the United States, 2005–2007: preliminary results. Semin Nucl Med. 2008;38(5):384–91.

    Article  PubMed  Google Scholar 

  16. Huang CJ, Jap TS. A systematic review of genetic studies of thyroid disorders in Taiwan. J Chin Med Assoc. 2015;78(3):145–53.

    Article  PubMed  Google Scholar 

  17. Sarika L, Papathoma A, Garofalaki M, et al. Genetic screening of patients with medullary thyroid cancer (MTC) in a referral center in Greece during the past two decades. Eur J Endocrinol. 2015;172(4):501–9.

    Article  CAS  PubMed  Google Scholar 

  18. American Thyroid Association Guidelines Task Force, Kloos RT, Eng C, Evans DB, Francis GL, Gagel RF, Gharib H, et al. Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid. 2009;19:565–612.

    Article  Google Scholar 

  19. Elisei R, Alevizaki M, Conte-Devolx B, Frank-Raue K, Leite V, Williams GR. European Thyroid Association guidelines for genetic testing and its clinical consequences in medullary thyroid cancer. Eur Thyroid J. 2012;1:216–31.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Haymart MR, Repplinger DJ, Leverson GE, et al. Higher serum thyroid stimulating hormone level in thyroid nodule patients is associated with greater risks of differentiated thyroid cancer and advanced tumor stage. J Clin Endocrinol Metab. 2008;93(3):809–1.

    Article  CAS  PubMed  Google Scholar 

  21. Liu CL, Cheng SP, Lin HW, Lai YL. Risk of thyroid cancer in patients with thyroiditis: a population-based cohort study. Ann Surg Oncol. 2014;21(3):843–9.

    Article  CAS  PubMed  Google Scholar 

  22. Dal Maso L, Bosetti C, La Vecchia C, Franceschi S. Risk factors for thyroid cancer: an epidemiological review focused on nutritional factors. Cancer Causes Control. 2009;20(1):75–86.

    Article  PubMed  Google Scholar 

  23. Ma J, Huang M, Wang L, Ye W, et al. Obesity and risk of thyroid cancer: evidence from a meta-analysis of 21 observational studies. Med Sci Monit. 2015;21:283–91.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Sakoda LC, Horn-Ross PL. Reproductive and menstrual history and papillary thyroid cancer risk: the San Francisco Bay Area thyroid cancer study. Cancer Epidemiol Biomark Prev. 2002;11(1):51–7.

    Google Scholar 

  25. Boas M, Main KM, Feldt-Rasmussen U. Environmental chemicals and thyroid function: an update. Curr Opin Endocrinol Diabetes Obes. 2009;16(5):385–91.

    Article  CAS  PubMed  Google Scholar 

  26. Capen CC. Mechanistic data and risk assessment of selected toxic end points of the thyroid gland. Toxicol Pathol. 1997;25(1):39–48.

    Article  CAS  PubMed  Google Scholar 

  27. Kufe DW, Pollock RE, Weichselbaum RR, et al. Holland-Frei cancer medicine. 6th ed. Hamilton: BC Decker; 2003.

    Google Scholar 

  28. Perros P, Boelaert K, Colley S, Evans C, Evans RM, Gerrard Ba G, Gilbert J, Harrison B, Johnson SJ, Giles TE, Moss L, Lewington V, Newbold K, Taylor J, Thakker RV, Watkinson J, Williams GR, British Thyroid Association. Guidelines for the management of thyroid cancer. Clin Endocrinol. 2014;81(Suppl 1):1–122.

    Article  CAS  Google Scholar 

  29. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid. 2016;26:1–133.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Seethala RR, Asa SL, Cart SE, Hodak SP, McHugh JB, Shah J, Thompson LDR, Nikiforov YE. Protocol for the examination of specimens from patients with carcinomas of the thyroid gland. Version Thyroid 3.1.0.0 College of American Pathologists. Available from: www.cap.org/apps/docs/committees/cancer/cancer_protocols/2014/Thyroid_ 14Protocol_3100.pdf. Accessed 31 Mar 2017.

  31. Elsheikh TM, Asa SL, Chan JKC, DeLellis RA, Heffess CS, Livolsi VA, et al. Interobserver and intraobserver variation among experts in the diagnosis of thyroid follicular lesions with borderline nuclear features of papillary carcinoma. Am J Clin Pathol. 2008;130:736–44.

    Article  PubMed  Google Scholar 

  32. Verburg FA, Aktolun C, Chiti A, et al. Why the European Association of Nuclear Medicine has declined to endorse the 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer. Eur J Nucl Med Mol Imaging. 2016;43:1001–5. https://doi.org/10.1007/s00259-016-3327-3.

    Article  PubMed  Google Scholar 

  33. Luster M, Clarke SE, Dietlein M, Lassmann M, Lind P, Oyen WJ, et al. Guidelines for radioiodine therapy of differentiated thyroid cancer. Eur J Nucl Med Mol Imaging. 2008;35:1941–59.

    Article  CAS  PubMed  Google Scholar 

  34. Frangos S, Iakovou IP, Marlowe RJ, Eftychiou N, Patsali L, Vanezi A, et al. Difficulties in deciding whether to ablate patients with putatively “low-intermediate-risk” differentiated thyroid carcinoma: do guidelines mainly apply in the centres that produce them? Results of a retrospective, two-centre quality assurance study. Eur J Nucl Med Mol Imaging. 2015;42:2045–55.

    Article  PubMed  Google Scholar 

  35. Schneider DF, Sippel RS. Measuring quality in thyroid cancer surgery. Adv Endocrinol. 2014;2014:1–6.https://doi.org/10.1155/2014/714291. Article ID 714291.

  36. NCCN Clinical Practice Guidelines in Oncology. www.nccn.org. [Online]; 2017 [cited 2017 April 8]. Available from: https://www.nccn.org/professionals/physician_gls/PDF/thyroid.pdf.

  37. Lifante JC, Duclos A, Couray-Targe S, Colin C, Peix JL, Schott AM. Hospital volume influences the choice of operation for thyroid cancer. Br J Surg. 2009;96(11):1284–8.

    Article  CAS  PubMed  Google Scholar 

  38. Pieracci FM, Fahey TJ III. Effect of hospital volume of thyroidectomies on outcomes following substernal thyroidectomy. World J Surg. 2008;32(5):740–6.

    Article  PubMed  Google Scholar 

  39. Kocher A. Discussion on partial thyroidectomy under local anaesthesia, with special reference to exophthalmic goitre. Proc R Soc Med. 1912;5:89–96.

    PubMed Central  Google Scholar 

  40. Coorough NE, Schneider DF, Rosen MW, et al. A survey of preferences regarding surgical approach to thyroid surgery. World J Surg. 2014;38:696–703.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Terris DJ, Snyder S, Carneiro-Pla D, et al. American Thyroid Association statement on outpatient thyroidectomy. Thyroid. 2013;23(10):1193–202.

    Article  PubMed  Google Scholar 

  42. Balentine CJ, Sippel RS. Outpatient thyroidectomy: is it safe?. In: Surgical oncology clinics of North America, vol. 25, Number 1. Philadelphia: Elsevier; 2015. p. 61–76.

    Google Scholar 

  43. Grubbs EG, Evans DB. Role of lymph node dissection in primary surgery for thyroid cancer. J Natl Compr Cancer Netw. 2007;5:623–30.

    Article  Google Scholar 

  44. Qubain SW, Nakano S, Baba M, et al. Distribution of lymph node micrometastasis in pN0 well-differentiated thyroid carcinoma. Surgery. 2002;131:249–56.

    Article  PubMed  Google Scholar 

  45. Grant CS. Recurrence of papillary thyroid cancer after optimized surgery. Gland Surg. 2015;4:52–62.

    PubMed  PubMed Central  Google Scholar 

  46. Durante C, Montesano T, Torlontano M, et al. Papillary thyroid cancer: time course of recurrences during postsurgery surveillance. J Clin Endocrinol Metab. 2013;98:636–42.

    Article  CAS  PubMed  Google Scholar 

  47. Robenshtok E, Fish S, Bach A, Domínguez JM, Shaha A, Tuttle RM. Suspicious cervical lymph nodes detected after thyroidectomy for papillary thyroid cancer usually remain stable over years in properly selected patients. J Clin Endocrinol Metab. 2012;97(8):2706–13.

    Article  CAS  PubMed  Google Scholar 

  48. Giovanella L, Bongiovanni M, Trimboli P. Diagnostic value of thyroglobulin assay in cervical lymph node fine-needle aspirations for metastatic differentiated thyroid cancer. Curr Opin Oncol. 2013;25:6–13.

    Article  CAS  PubMed  Google Scholar 

  49. Smithers DW. Some varied applications of radioactive isotopes to the localization and treatment of tumors. Acta Radiol. 1951;35(1):49–61.

    Article  CAS  PubMed  Google Scholar 

  50. Dai G, Levy O, Carrasco N. Cloning and characterization of the thyroid iodide transporter. Nature. 1996;379:458–60.

    Article  CAS  PubMed  Google Scholar 

  51. Smanik PA, Ryu KY, Theil KS, Mazzaferri EL, Jhiang SM. Expression, exon-intron organization, and chromosome mapping of the human sodium iodide symporter. Endocrinology. 1997;138:3555–8.

    Article  CAS  PubMed  Google Scholar 

  52. Dohan O, De la Vieja A, Paroder V, Riedel C, Artani M, Reed M, et al. The sodium/iodide Symporter (NIS): characterization, regulation, and medical significance. Endocr Rev. 2003;24:48–77.

    Article  CAS  PubMed  Google Scholar 

  53. Castro MR, Bergert ER, Goellner JR, Hay ID, Morris JC. Immunohistochemical analysis of sodium iodide symporter expression in metastatic differentiated thyroid cancer: correlation with radioiodine uptake. J Clin Endocrinol Metab. 2001;86:5627–32.

    Article  CAS  PubMed  Google Scholar 

  54. Wapnir IL, van de Rijn M, Nowels K, Amenta PS, Walton K, Montgomery K, et al. Immunohistochemical profile of the sodium/iodide symporter in thyroid, breast, and other carcinomas using high density tissue microarrays and conventional sections. J Clin Endocrinol Metab. 2003;88:1880–8.

    Article  CAS  PubMed  Google Scholar 

  55. Freudenberg LS, Jentzen W, Stahl A, et al. Clinical applications of 124I-PET/CT in patients with differentiated thyroid cancer. Eur J Nucl Med Mol Imaging. 2011;38(Suppl 1):48–56. https://doi.org/10.1007/s00259-011-1773-5.

    Article  Google Scholar 

  56. Phillips AF, Haybittle JL, Newberry GR. Use of iodine-124 for the treatment of carcinoma of the thyroid. Acta Unio Int Contra Cancrum. 1960;16:1434–8.

    CAS  PubMed  Google Scholar 

  57. Lassmann M, Reiners C, Luster M. Dosimetry and thyroid cancer: the individual dosage of radioiodine. Endocr Relat Cancer. 2010;17(3):R161–72.

    Article  CAS  PubMed  Google Scholar 

  58. Freudenberg LS, Antoch G, Knust J, Görges R, Müller SP, Bockisch A, et al. Value of 124I-PET/CT in staging of patients with differentiated thyroid cancer. Eur Radiol. 2004;14:2092–8.

    Article  CAS  PubMed  Google Scholar 

  59. Freudenberg LS, Jentzen W, Petrich T, Frömke C, Marlowe RJ, Heusner T, et al. Lesion dose in differentiated thyroid carcinoma metastases after rhTSH or thyroid hormone withdrawal: 124I PET/CT dosimetric comparisons. Eur J Nucl Med Mol Imaging. 2010;37:2267–76.

    Article  CAS  PubMed  Google Scholar 

  60. Strauss LG, Conti PS. The application of PET in clinical oncology. J Nucl Med. 1991;32:623–48.

    CAS  PubMed  Google Scholar 

  61. Ain KB, Taylor KD, Tofiq S, Venkataraman G. Somatostatin receptor subtype expression in human thyroid and thyroid carcinoma cell lines. J Clin Endocrinol Metab. 1997;82:1857–62.

    CAS  PubMed  Google Scholar 

  62. Cohen EE, Rosen LS, Vokes EE, et al. Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II study. J Clin Oncol. 2008;26(29):4708–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Kundu P, Lata S, Sharma P, et al. Eur J Nucl Med Mol Imaging. 2014;41:1354. https://doi.org/10.1007/s00259-014-2723-9.

    Article  CAS  PubMed  Google Scholar 

  64. Chrisoulidou A, Mandanas S, Margaritidou E, et al. Treatment compliance and severe adverse events limit the use of tyrosine kinase inhibitors in refractory thyroid cancer. Onco Targets Ther. 2015;8:2435–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Leboulleux S, Bastholt L, Krause T, et al. Vandetanib in locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 2 trial. Lancet Oncol. 2012;13(9):897–905.

    Article  CAS  PubMed  Google Scholar 

  66. Brose MS, Nutting CM, Jarzab B, et al. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial. Lancet. 2014;384(9940):319–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Bible KC, Suman VJ, Molina JR, et al. Efficacy of pazopanib in progressive, radioiodine-refractory, metastatic differentiated thyroid cancers: results of a phase 2 consortium study. Lancet Oncol. 2010;11(10):962–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Carr LL, Mankoff DA, Goulart BH, et al. 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(21):5260–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Sherman SI, Clary DO, Elisei R, et al. Correlative analyses of RET and RAS mutations in a phase 3 trial of cabozantinib in patients with progressive, metastatic medullary thyroid cancer. Cancer. 2016;122(24):3856–64.

    Article  CAS  PubMed  Google Scholar 

  70. Viola D, Valerio L, Molinaro E, et al. Treatment of advanced thyroid cancer with targeted therapies: ten years of experience. Endocr Relat Cancer. 2016;23(4):R185–205.

    Article  CAS  PubMed  Google Scholar 

  71. Chakravarty D, Santos E, Ryder M, et al. Small-molecule MAPK inhibitors restore radioiodine incorporation in mouse thyroid cancers with conditional BRAF activation. J Clin Invest. 2011;121(12):4700–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Ho AL, Grewal RK, Leboeuf R, et al. Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer. N Engl J Med. 2013;368(7):623–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Grewal RK, Ho A, Schöder H, et al. Novel approaches to thyroid cancer treatment and response assessment. Semin Nucl Med. 2016;46(2):109–18.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Schlumberger M, Sherman SI. Approach to the patient with advanced differentiated thyroid cancer. Eur J Endocrinol. 2012;166(1):5–11.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Nuclear Medicine, Bank of Cyprus Oncology Centre, Nicosia, Cyprus

    Savvas Frangos

  2. Department of Nuclear Medicine, Aristotle University, Papageorgiou Hospital, Thessaloniki, Greece

    Ioannis Iakovou

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  1. Savvas Frangos
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  2. Ioannis Iakovou
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Correspondence to Savvas Frangos .

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Editors and Affiliations

  1. Department of Nuclear Medicine, Humanitas Gavazzeni Hospital, Bergamo, Italy

    Emilio Bombardieri

  2. Nuclear Medicine Therapy and Endocrinology, Istituto Nazionale dei Tumori, Milano, Italy

    Ettore Seregni

  3. Nuclear Medicine and Molecular Imaging Unit, Veneto Institute of Oncology IOV - IRCCS, Padova, Italy

    Laura Evangelista

  4. Nuclear Medicine Division, Istituto Nazionale dei Tumori, Milano, Italy

    Carlo Chiesa

  5. Nuclear Medicine, Humanitas Research Hospital, Rozzano, Milano, Italy

    Arturo Chiti

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Frangos, S., Iakovou, I. (2018). New Approaches in the Management of Thyroid Cancer. In: Bombardieri, E., Seregni, E., Evangelista, L., Chiesa, C., Chiti, A. (eds) Clinical Applications of Nuclear Medicine Targeted Therapy . Springer, Cham. https://doi.org/10.1007/978-3-319-63067-0_5

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