Skip to main content
SpringerLink
Log in

The Role of Targeted Therapies or Nonsurgical Treatment of Thyroid Malignancies: Is Surgery Being Replaced?

  • Chapter
Controversies in Thyroid Surgery

  • 1140 Accesses

Abstract

Targeted therapies are emerging rapidly and are challenging the traditional roles of nonsurgical therapy for the treatment of thyroid cancers. Molecular pathways hold the key for designing rationally based drugs such as the already FDA-approved tyrosine kinase inhibitors: sorafenib, vandetanib, and cabozantinib. Many more targeted therapies are under investigation. For instance, selumetinib is a MEK inhibitor that has been shown to restore radioiodine avidity to radioiodine refractory thyroid cancers. This chapter reviews standard nonsurgical treatments including the historical use of cytotoxic chemotherapy, the molecular science behind newly approved and experimental targeted agents, and their supporting clinical trial data. Lastly, the chapter presents four common scenarios in thyroid cancer management where an increased role is forthcoming for nonsurgical modalities such as tyrosine kinase inhibitors. These cases contrast the cutting edge use of pharmacology, as monotherapy or in combination, with the current held standard of care. Nonsurgical modalities for thyroid cancer care are rapidly advancing, and the best use of these modalities has yet to be established as highlighted in the cases.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 54.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

Akt:

Also known as protein kinase B

Braf:

v-raf murine sarcoma viral oncogene homolog B1l DNA, deoxyribonucleic acid

ERK:

Extracellular signal-regulated kinases

HDAC:

Histone deacetylase inhibitor

Mek:

Mitogen-activated protein kinase

mTOR:

Mammalian target of rapamycin

PI3K:

Phosphoinositide 3-kinase

Ras:

Rat sarcoma proteins

RET TKR:

Rearranged during transfection tyrosine kinase receptor

TKR:

Tyrosine kinase receptor

VEGFR:

Vascular endothelial growth factor receptor

References

  1. Nikiforov YE, Nikiforova MN. Molecular genetics and diagnosis of thyroid cancer. Nat Rev Endocrinol. 2011;7(10):569–80.

    Article  CAS  PubMed  Google Scholar 

  2. Nixon IJ, Whitcher MM, Palmer FL, et al. The impact of distant metastases at presentation on prognosis in patients with differentiated carcinoma of the thyroid gland. Thyroid. 2012;22(9):884–9.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Durante C, Haddy N, Baudin E, et al. Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: benefits and limits of radioiodine therapy. J Clin Endocrinol Metab. 2006;91(8):2892–9.

    Article  CAS  PubMed  Google Scholar 

  4. Capdevila J, Argiles G, Rodriguez-Frexinos V, Nunez I, Tabernero J. New approaches in the management of radioiodine-refractory thyroid cancer: the molecular targeted therapy era. Discov Med. 2010;9(45):153–62.

    PubMed  Google Scholar 

  5. Eustatia-Rutten CF, Corssmit EP, Biermasz NR, Pereira AM, Romijn JA, Smit JW. Survival and death causes in differentiated thyroid carcinoma. J Clin Endocrinol Metab. 2006;91(1):313–9.

    Article  CAS  PubMed  Google Scholar 

  6. Papaleontiou M, Haymart MR. New insights in risk stratification of differentiated thyroid cancer. Curr Opin Oncol. 2014;26(1):1–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Shaha AR, Shah JP, Loree TR. Risk group stratification and prognostic factors in papillary carcinoma of thyroid. Ann Surg Oncol. 1996;3(6):534–8.

    Article  CAS  PubMed  Google Scholar 

  8. Brierley JD, Panzarella T, Tsang RW, Gospodarowicz MK, O’Sullivan B. A comparison of different staging systems predictability of patient outcome. Thyroid carcinoma as an example. Cancer. 1997;79(12):2414–23.

    Article  CAS  PubMed  Google Scholar 

  9. Sherman SI, Brierley JD, Sperling M, et al. Prospective multicenter study of thyroiscarcinoma treatment: initial analysis of staging and outcome. National Thyroid Cancer Treatment Cooperative Study Registry Group. Cancer. 1998;83(5):1012–21.

    Article  CAS  PubMed  Google Scholar 

  10. Brose MS, Smit J, Capdevila J, et al. Regional approaches to the management of patients with advanced, radioactive iodine-refractory differentiated thyroid carcinoma. Expert Rev Anticancer Ther. 2012;12(9):1137–47.

    Article  CAS  PubMed  Google Scholar 

  11. Hay ID, Grant CS, Taylor WF, McConahey WM. Ipsilateral lobectomy versus bilateral lobar resection in papillary thyroid carcinoma: a retrospective analysis of surgical outcome using a novel prognostic scoring system. Surgery. 1987;102(6):1088–95.

    CAS  PubMed  Google Scholar 

  12. Hay ID, Bergstralh EJ, Goellner JR, Ebersold JR, Grant CS. 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;114(6):1050–7. discussion 1057–1058.

    CAS  PubMed  Google Scholar 

  13. Byar DP, Green SB, Dor P, et al. A prognostic index for thyroid carcinoma. A study of the E.O.R.T.C. Thyroid Cancer Cooperative Group. Eur J Cancer. 1979;15(8):1033–41.

    Article  CAS  PubMed  Google Scholar 

  14. Dean DS, Hay ID. Prognostic indicators in differentiated thyroid carcinoma. Cancer Control. 2000;7(3):229–39.

    CAS  PubMed  Google Scholar 

  15. Verburg FA, Mader U, Kruitwagen CL, Luster M, Reiners C. A comparison of prognostic classification systems for differentiated thyroid carcinoma. Clin Endocrinol (Oxf). 2010;72(6):830–8.

    Article  Google Scholar 

  16. Chen AY, Jemal A, Ward EM. Increasing incidence of differentiated thyroid cancer in the United States, 1988–2005. Cancer. 2009;115(16):3801–7.

    Article  PubMed  Google Scholar 

  17. Vas Nunes JH, Clark JR, Gao K, et al. Prognostic implications of lymph node yield and lymph node ratio in papillary thyroid carcinoma. Thyroid. 2013;23(7):811–6.

    Article  PubMed  Google Scholar 

  18. Pujol P, Daures JP, Nsakala N, Baldet L, Bringer J, Jaffiol C. Degree of thyrotropin suppression as a prognostic determinant in differentiated thyroid cancer. J Clin Endocrinol Metab. 1996;81(12):4318–23.

    CAS  PubMed  Google Scholar 

  19. McLeod DS. Thyrotropin in the development and management of differentiated thyroid cancer. Endocrinol Metab Clin North Am. 2014;43(2):367–83.

    Article  PubMed  Google Scholar 

  20. Fiore E, Vitti P. Serum TSH and risk of papillary thyroid cancer in nodular thyroid disease. J Clin Endocrinol Metab. 2012;97(4):1134–45.

    Article  CAS  PubMed  Google Scholar 

  21. Haymart MR, Glinberg SL, Liu J, Sippel RS, Jaume JC, Chen H. Higher serum TSH in thyroid cancer patients occurs independent of age and correlates with extrathyroidal extension. Clin Endocrinol (Oxf). 2009;71(3):434–9.

    Article  CAS  Google Scholar 

  22. Prescott JD, Sadow PM, Hodin RA, et al. BRAF V600E status adds incremental value to current risk classification systems in predicting papillary thyroid carcinoma recurrence. Surgery. 2012;152(6):984–90.

    Article  PubMed Central  PubMed  Google Scholar 

  23. Rusinek D, Szpak-Ulczok S, Jarzab B. Gene expression profile of human thyroid cancer in relation to its mutational status. J Mol Endocrinol. 2011;47(3):R91–103.

    Article  CAS  PubMed  Google Scholar 

  24. Schlumberger M, Brose M, Elisei R, et al. Definition and management of radioactive iodine-refractory differentiated thyroid cancer. Lancet Diabetes Endocrinol. 2014;2(5):356–8.

    Article  PubMed  Google Scholar 

  25. Maxwell JE, Sherman SK, O’Dorisio TM, Howe JR. Medical management of metastatic medullary thyroid cancer. Cancer. 2014;120:3287–301.

    Article  PubMed  PubMed Central  Google Scholar 

  26. 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  PubMed Central  CAS  PubMed  Google Scholar 

  27. Gottlieb JA, Hill Jr CS, Ibanez ML, Clark RL. Chemotherapy of thyroid cancer. An evaluation of experience with 37 patients. Cancer. 1972;30(3):848–53.

    Article  CAS  PubMed  Google Scholar 

  28. Gottlieb JA, Hill Jr CS. Chemotherapy of thyroid cancer with adriamycin. Experience with 30 patients. N Engl J Med. 1974;290(4):193–7.

    Article  CAS  PubMed  Google Scholar 

  29. Matuszczyk A, Petersenn S, Bockisch A, et al. Chemotherapy with doxorubicin in progressive medullary and thyroid carcinoma of the follicular epithelium. Horm Metab Res. 2008;40(3):210–3. doi:10.1055/s-2008-1046781.

    Article  CAS  PubMed  Google Scholar 

  30. Williams SD, Birch R, Einhorn LH. Phase II evaluation of doxorubicin plus cisplatin in advanced thyroid cancer: a Southeastern Cancer Study Group Trial. Cancer Treat Rep. 1986;70(3):405–7.

    CAS  PubMed  Google Scholar 

  31. Shimaoka K, Schoenfeld DA, DeWys WD, Creech RH, DeConti R. A randomized trial of doxorubicin versus doxorubicin plus cisplatin in patients with advanced thyroid carcinoma. Cancer. 1985;56(9):2155–60.

    Article  CAS  PubMed  Google Scholar 

  32. Matuszczyk A, Petersenn S, Voigt W, et al. Chemotherapy with paclitaxel and gemcitabine in progressive medullary and thyroid carcinoma of the follicular epithelium. Horm Metab Res. 2010;42(1):61–4. doi:10.1055/s-0029-1238294. Epub 1232009 Sep 1238294.

    Article  CAS  PubMed  Google Scholar 

  33. Santini F, Bottici V, Elisei R, et al. Cytotoxic effects of carboplatinum and epirubicin in the setting of an elevated serum thyrotropin for advanced poorly differentiated thyroid cancer. J Clin Endocrinol Metab. 2002;87(9):4160–5.

    Article  CAS  PubMed  Google Scholar 

  34. Besic N, Auersperg M, Gazic B, Dremelj M, Zagar I. Neoadjuvant chemotherapy in 29 patients with locally advanced follicular or Hurthle cell thyroid carcinoma: a phase 2 study. Thyroid. 2012;22(2):131–7. doi:10.1089/thy.2011.0243. Epub 2011 Dec 1016.

    Article  CAS  PubMed  Google Scholar 

  35. Besic N, Auersperg M, Dremelj M, Vidergar-Kralj B, Gazic B. Neoadjuvant chemotherapy in 16 patients with locally advanced papillary thyroid carcinoma. Thyroid. 2013;23(2):178–84. doi:10.1089/thy.2012.0194.

    Article  CAS  PubMed  Google Scholar 

  36. Carlomagno F, Santoro M. Thyroid cancer in 2010: a roadmap for targeted therapies. Nat Rev Endocrinol. 2011;7(2):65–7.

    Article  CAS  PubMed  Google Scholar 

  37. Xing M. Molecular pathogenesis and mechanisms of thyroid cancer. Nat Rev Cancer. 2013;13(3):184–99.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Pratilas CA, Taylor BS, Ye Q, et al. (V600E)BRAF is associated with disabled feedback inhibition of RAF-MEK signaling and elevated transcriptional output of the pathway. Proc Natl Acad Sci USA. 2009;106(11):4519–24.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Kimura ET, Nikiforova MN, Zhu Z, Knauf JA, Nikiforov YE, Fagin JA. 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;63(7):1454–7.

    CAS  PubMed  Google Scholar 

  40. Soares P, Maximo V, Sobrinho-Simoes M. Molecular pathology of papillary, follicular and Hurthle cell carcinomas of the thyroid. Arkh Patol. 2003;65(2):45–7.

    PubMed  Google Scholar 

  41. Nikiforova MN, Kimura ET, Gandhi M, et al. BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas. J Clin Endocrinol Metab. 2003;88(11):5399–404.

    Article  CAS  PubMed  Google Scholar 

  42. Ricarte-Filho JC, Ryder M, Chitale DA, et al. Mutational profile of advanced primary and metastatic radioactive iodine-refractory thyroid cancers reveals distinct pathogenetic roles for BRAF, PIK3CA, and AKT1. Cancer Res. 2009;69(11):4885–93.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Franco AT, Malaguarnera R, Refetoff S, et al. Thyrotropin receptor signaling dependence of Braf-induced thyroid tumor initiation in mice. Proc Natl Acad Sci USA. 2011;108(4):1615–20.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Durante C, Puxeddu E, Ferretti E, et al. BRAF mutations in papillary thyroid carcinomas inhibit genes involved in iodine metabolism. J Clin Endocrinol Metab. 2007;92(7):2840–3.

    Article  CAS  PubMed  Google Scholar 

  45. Espadinha C, Santos JR, Sobrinho LG, Bugalho MJ. Expression of iodine metabolism genes in human thyroid tissues: evidence for age and BRAFV600E mutation dependency. Clin Endocrinol (Oxf). 2009;70(4):629–35.

    Article  CAS  Google Scholar 

  46. Romei C, Ciampi R, Faviana P, et al. BRAFV600E mutation, but not RET/PTC rearrangements, is correlated with a lower expression of both thyroperoxidase and sodium iodide symporter genes in papillary thyroid cancer. Endocr Relat Cancer. 2008;15(2):511–20.

    Article  CAS  PubMed  Google Scholar 

  47. 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  PubMed Central  CAS  PubMed  Google Scholar 

  48. Knauf JA, Ouyang B, Croyle M, Kimura E, Fagin JA. Acute expression of RET/PTC induces isozyme-specific activation and subsequent downregulation of PKCepsilon in PCCL3 thyroid cells. Oncogene. 2003;22(44):6830–8.

    Article  CAS  PubMed  Google Scholar 

  49. De Vita G, Bauer L, da Costa VM, et al. Dose-dependent inhibition of thyroid differentiation by RAS oncogenes. Mol Endocrinol. 2005;19(1):76–89.

    Article  PubMed  CAS  Google Scholar 

  50. Karras S, Anagnostis P, Krassas GE. Vandetanib for the treatment of thyroid cancer: an update. Expert Opin Drug Metab Toxicol. 2014;10(3):469–81.

    Article  CAS  PubMed  Google Scholar 

  51. Wells Jr SA, Robinson BG, Gagel RF, et al. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol. 2012;30(2):134–41.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  52. Colombo JR, Wein RO. Cabozantinib for progressive metastatic medullary thyroid cancer: a review. Ther Clin Risk Manag. 2014;10:395–404.

    PubMed Central  PubMed  Google Scholar 

  53. Karras S, Pontikides N, Krassas GE. Pharmacokinetic evaluation of cabozantinib for the treatment of thyroid cancer. Expert Opin Drug Metab Toxicol. 2013;9(4):507–15.

    Article  CAS  PubMed  Google Scholar 

  54. Kurzrock R, Sherman SI, Ball DW, et al. Activity of XL184 (Cabozantinib), an oral tyrosine kinase inhibitor, in patients with medullary thyroid cancer. J Clin Oncol. 2011;29(19):2660–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  55. Elisei R, Schlumberger MJ, Muller SP, et al. Cabozantinib in progressive medullary thyroid cancer. J Clin Oncol. 2013;31(29):3639–46.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  56. UpToDate. Vandetanib Patient Information 2014; http://eresources.library.mssm.edu:2226/contents/vandetanib-drug-information?source=search_result&search=vandetanib&selectedTitle=1%7E21#F12746025. Accessed September 30th, 2014, 2014.

  57. 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  PubMed Central  CAS  PubMed  Google Scholar 

  58. Grande E, Diez JJ, Zafon C, Capdevila J. Thyroid cancer: molecular aspects and new therapeutic strategies. J Thyroid Res. 2012;2012:847108.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  59. Stjepanovic N, Capdevila J. Multikinase inhibitors in the treatment of thyroid cancer: specific role of lenvatinib. Biologics. 2014;8:129–39.

    PubMed Central  PubMed  Google Scholar 

  60. Schlumberger M. A phase 3, multicenter, double-blind, placebo-controlled trial of lenvatinib (E7080) in patients with 131I-refractory differentiated thyroid cancer (SELECT). Paper presented at: 2014 ASCO Annual Meeting 2013; Chicago, IL

    Google Scholar 

  61. Kloos RT, Ringel MD, Knopp MV, et al. Phase II trial of sorafenib in metastatic thyroid cancer. J Clin Oncol. 2009;27(10):1675–84.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  62. Lam ET, Ringel MD, Kloos RT, et al. Phase II clinical trial of sorafenib in metastatic medullary thyroid cancer. J Clin Oncol. 2010;28(14):2323–30.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  63. 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 

  64. Anderson RT, Linnehan JE, Tongbram V, Keating K, Wirth LJ. Clinical, safety, and economic evidence in radioactive iodine-refractory differentiated thyroid cancer: a systematic literature review. Thyroid. 2013;23(4):392–407.

    Article  CAS  PubMed  Google Scholar 

  65. 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  Google Scholar 

  66. Nixon IJ, Shaha AR, Tuttle MR. Targeted therapy in thyroid cancer. Curr Opin Otolaryngol Head Neck Surg. 2013;21(2):130–4.

    Article  PubMed  Google Scholar 

  67. Haraldsdottir S, Shah MH. An update on clinical trials of targeted therapies in thyroid cancer. Curr Opin Oncol. 2014;26(1):36–44.

    Article  CAS  PubMed  Google Scholar 

  68. Antonelli A, Fallahi P, Ferrari SM, et al. New targeted therapies for thyroid cancer. Curr Genomics. 2011;12(8):626–31.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  69. 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  PubMed Central  CAS  PubMed  Google Scholar 

  70. 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  PubMed Central  CAS  PubMed  Google Scholar 

  71. Schlumberger MJ, Elisei R, Bastholt L, et al. Phase II study of safety and efficacy of motesanib in patients with progressive or symptomatic, advanced or metastatic medullary thyroid cancer. J Clin Oncol. 2009;27(23):3794–801.

    Article  CAS  PubMed  Google Scholar 

  72. Sherman EJ Ho A, Fury MG, et al. . A phase II study of temsirolimus/sorafenib in patients with radioactive iodine (RAI)-refractory thyroid carcinoma. J Clin Oncol. 2012;23(abstract Suppl: A5514).

    Google Scholar 

  73. McFarland DC, Misiukiewicz KJ. Sorafenib in radioactive iodine-refractory well-differentiated metastatic thyroid cancer. OncoTargets Ther. 2014;7:1291–9.

    Article  CAS  Google Scholar 

  74. Gild ML, Bullock M, Robinson BG, Clifton-Bligh R. Multikinase inhibitors: a new option for the treatment of thyroid cancer. Nat Rev Endocrinol. 2011;7(10):617–24.

    Article  CAS  PubMed  Google Scholar 

  75. Dadu R, Devine C, Hernandez M, et al. Role of salvage targeted therapy in differentiated thyroid cancer patients who failed first-line sorafenib. J Clin Endocrinol Metab. 2014;99(6):2086–94.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  76. Hayes DN, Lucas AS, Tanvetyanon T, et al. Phase II efficacy and pharmacogenomic study of Selumetinib (AZD6244; ARRY-142886) in iodine-131 refractory papillary thyroid carcinoma with or without follicular elements. Clin Cancer Res. 2012;18(7):2056–65.

    Article  CAS  PubMed  Google Scholar 

  77. Wang S, Chen L. Immunobiology of cancer therapies targeting CD137 and B7-H1/PD-1 cosignal pathways. Curr Top Microbiol Immunol. 2011;344:245–67.

    CAS  PubMed  Google Scholar 

  78. Saverino D, Brizzolara R, Simone R, et al. Soluble CTLA-4 in autoimmune thyroid diseases: relationship with clinical status and possible role in the immune response dysregulation. Clin Immunol. 2007;123(2):190–8.

    Article  CAS  PubMed  Google Scholar 

  79. Lu J, Lee-Gabel L, Nadeau MC, Ferencz TM, Soefje SA. Clinical evaluation of compounds targeting PD-1/PD-L1 pathway for cancer immunotherapy. J Oncol Pharm Prac. 2014:1–17.

    Google Scholar 

  80. Ito Y, Higashiyama T, Hirokawa M, et al. Clinical trial of weekly paclitaxel chemotherapy for papillary thyroid carcinoma with squamous cell carcinoma component. Endocr J. 2012;59(9):839–44.

    Article  CAS  PubMed  Google Scholar 

  81. Tennvall J, Lundell G, Hallquist A, Wahlberg P, Wallin G, Tibblin S. Combined doxorubicin, hyperfractionated radiotherapy, and surgery in anaplastic thyroid carcinoma. Report on two protocols The Swedish Anaplastic Thyroid Cancer Group. Cancer. 1994;74(4):1348–54.

    Article  CAS  PubMed  Google Scholar 

  82. Crouzeix G, Michels JJ, Sevin E, et al. Unusual short-term complete response to two regimens of cytotoxic chemotherapy in a patient with poorly differentiated thyroid carcinoma. J Clin Endocrinol Metab. 2012;97(9):3046–50.

    Article  CAS  PubMed  Google Scholar 

  83. McCarthy RP, Wang M, Jones TD, Strate RW, Cheng L. Molecular evidence for the same clonal origin of multifocal papillary thyroid carcinomas. Clin Cancer Res. 2006;12(8):2414–8.

    Article  CAS  PubMed  Google Scholar 

  84. Honings J, Stephen AE, Marres HA, Gaissert HA. The management of thyroid carcinoma invading the larynx or trachea. Laryngoscope. 2010;120(4):682–9.

    Article  PubMed  Google Scholar 

  85. Kim KB, Cabanillas ME, Lazar AJ, et al. Clinical responses to vemurafenib in patients with metastatic papillary thyroid cancer harboring BRAF(V600E) mutation. Thyroid. 2013;23(10):1277–83.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  86. Kim JH, Leeper RD. Combination adriamycin and radiation therapy for locally advanced carcinoma of the thyroid gland. Int J Radiat Oncol Biol Phys. 1983;9(4):565–7.

    Article  CAS  PubMed  Google Scholar 

  87. Mahler C, Verhelst J, de Longueville M, Harris A. Long-term treatment of metastatic medullary thyroid carcinoma with the somatostatin analogue octreotide. Clin Endocrinol (Oxf). 1990;33(2):261–9.

    Article  CAS  Google Scholar 

  88. Modigliani E, Cohen R, Joannidis S, et al. Results of long-term continuous subcutaneous octreotide administration in 14 patients with medullary thyroid carcinoma. Clin Endocrinol (Oxf). 1992;36(2):183–6.

    Article  CAS  Google Scholar 

  89. Janson ET, Oberg K. Long-term management of the carcinoid syndrome. Treatment with octreotide alone and in combination with alpha-interferon. Acta Oncol. 1993;32(2):225–9.

    Article  CAS  PubMed  Google Scholar 

  90. Skoura E. Depicting medullary thyroid cancer recurrence: the past and the future of nuclear medicine imaging. Int J Endocrinol Metab. 2013;11(4), e8156.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  91. Rufini V, Castaldi P, Treglia G, et al. Nuclear medicine procedures in the diagnosis and therapy of medullary thyroid carcinoma. Biomed Pharmacother. 2008;62(3):139–46.

    Article  CAS  PubMed  Google Scholar 

  92. Vainas I, Koussis C, Pazaitou-Panayiotou K, et al. Somatostatin receptor expression in vivo and response to somatostatin analog therapy with or without other antineoplastic treatments in advanced medullary thyroid carcinoma. J Exp Clin Cancer Res. 2004;23(4):549–59.

    CAS  PubMed  Google Scholar 

  93. American Thyroid Association Surgery Working Group, American Association of Endocrine Surgeons, American Academy of Otolaryngology-Head and Neck Surgery, et al. Consensus statement on the terminology and classification of central neck dissection for thyroid cancer. Thyroid. 2009;19(11):1153–8.

    Article  Google Scholar 

  94. Tuttle RM, Tala H, Shah J, et al. Estimating risk of recurrence in differentiated thyroid cancer after total thyroidectomy and radioactive iodine remnant ablation: using response to therapy variables to modify the initial risk estimates predicted by the new American Thyroid Association staging system. Thyroid. 2010;20(12):1341–9.

    Article  CAS  PubMed  Google Scholar 

  95. Vaisman F, Momesso D, Bulzico DA, et al. Spontaneous remission in thyroid cancer patients after biochemical incomplete response to initial therapy. Clin Endocrinol (Oxf). 2012;77(1):132–8.

    Article  CAS  Google Scholar 

  96. American Thyroid Association Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer, Cooper DS, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2009;19(11):1167–214.

    Article  Google Scholar 

  97. Cooper DK, Novitzky D, Wicomb WN, Basker M, Rosendale JD, Myron KH. A review of studies relating to thyroid hormone therapy in brain-dead organ donors. Front Biosci. 2009;14:3750–70.

    Article  CAS  Google Scholar 

  98. Rubino C, de Vathaire F, Dottorini ME, et al. Second primary malignancies in thyroid cancer patients. Br J Cancer. 2003;89(9):1638–44.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  99. Sawka AM, Thabane L, Parlea L, et al. Second primary malignancy risk after radioactive iodine treatment for thyroid cancer: a systematic review and meta-analysis. Thyroid. 2009;19(5):451–7.

    Article  CAS  PubMed  Google Scholar 

  100. Vaisman F, Tala H, Grewal R, Tuttle RM. In differentiated thyroid cancer, an incomplete structural response to therapy is associated with significantly worse clinical outcomes than only an incomplete thyroglobulin response. Thyroid. 2011;21(12):1317–22.

    Article  CAS  PubMed  Google Scholar 

  101. Pryma DA, Mandel SJ. Radioiodine therapy for thyroid cancer in the era of risk stratification and alternative targeted therapies. J Nucl Med. 2014;55(9):1485–91.

    Article  CAS  PubMed  Google Scholar 

  102. Efficace F, Cocks K, Breccia M, et al. Time for a new era in the evaluation of targeted therapies for patients with chronic myeloid leukemia: inclusion of quality of life and other patient-reported outcomes. Crit Rev Oncol Hematol. 2012;81(2):123–35.

    Article  CAS  PubMed  Google Scholar 

  103. Efficace F, Baccarani M, Rosti G, et al. Investigating factors associated with adherence behaviour in patients with chronic myeloid leukemia: an observational patient-centered outcome study. Br J Cancer. 2012;107(6):904–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  104. Mulder SF, Bertens D, Desar IM, et al. Impairment of cognitive functioning during Sunitinib or Sorafenib treatment in cancer patients: a cross sectional study. BMC Cancer. 2014;14:219.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  105. Gray SW, Hicks-Courant K, Lathan CS, Garraway L, Park ER, Weeks JC. Attitudes of patients with cancer about personalized medicine and somatic genetic testing. J Oncol Pract/Am Soc Clin Oncol. 2012;8(6):329–35. 322 p following 335.

    Article  Google Scholar 

  106. Scherubl H, Raue F, Ziegler R. Combination therapy with adriamycin, cisplatin and vindesine in C cell carcinoma of the thyroid. Onkologie. 1990;13(3):198–202.

    Article  CAS  PubMed  Google Scholar 

  107. Scherubl H, Raue F, Ziegler R. Combination chemotherapy of advanced medullary and differentiated thyroid cancer. Phase II study. J Cancer Res Clin Oncol. 1990;116(1):21–3.

    Article  CAS  PubMed  Google Scholar 

  108. Leaf AN, Wolf BC, Kirkwood JM, Haselow RE. Phase II study of etoposide (VP-16) in patients with thyroid cancer with no prior chemotherapy: an Eastern Cooperative Oncology Group Study (E1385). Med Oncol. 2000;17(1):47–51.

    Article  CAS  PubMed  Google Scholar 

  109. Ain KB, Egorin MJ, DeSimone PA. Treatment of anaplastic thyroid carcinoma with paclitaxel: phase 2 trial using ninety-six-hour infusion. Collaborative Anaplastic Thyroid Cancer Health Intervention Trials (CATCHIT) Group. Thyroid. 2000;10(7):587–94.

    Article  CAS  PubMed  Google Scholar 

  110. Sherman SI, Wirth LJ, Droz JP, et al. Motesanib diphosphate in progressive differentiated thyroid cancer. N Engl J Med. 2008;359(1):31–42.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Internal Medicine, Division of Hematology and Oncology, Mount Sinai Medical Center, New York, NY, USA

    Daniel C. McFarland D.O.

  2. Department of Otolaryngology—Head and Neck Surgery, Baylor College of Medicine, Houston, TX, USA

    Indu Varier M.D.

  3. Hematology and Medical Oncology, Mount Sinai Hospital, New York, NY, USA

    Krzysztof Misiukiewicz M.D., M.S.C.R.

Authors
  1. Daniel C. McFarland D.O.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Indu Varier M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Krzysztof Misiukiewicz M.D., M.S.C.R.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Daniel C. McFarland D.O. .

Editor information

Editors and Affiliations

  1. Department of Surgery; University of Virginia Health System, C Bruce Morton Professor and Chief; Division of General Surgery, Charlottesville, Virginia, USA

    John B. Hanks

  2. Chairman Department of Surgery, Mount Sinai Beth Israel, Eugene W Friedman Professor of Surgery; Icahn School of Medicine at Mount Sinai, New York, New York, USA

    William B. Inabnet III

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

McFarland, D.C., Varier, I., Misiukiewicz, K. (2016). The Role of Targeted Therapies or Nonsurgical Treatment of Thyroid Malignancies: Is Surgery Being Replaced?. In: Hanks, J., Inabnet III, W. (eds) Controversies in Thyroid Surgery. Springer, Cham. https://doi.org/10.1007/978-3-319-20523-6_17

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-20523-6_17

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-20522-9

  • Online ISBN: 978-3-319-20523-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation