Skip to main content
SpringerLink
Log in

Medullary Thyroid Cancer

  • Chapter
  • First Online:
Neuroendocrine Tumours

  • 10 Accesses

Abstract

Medullary thyroid cancer (MTC) is a neuroendocrine tumor that emerges from parafollicular or C cells of the thyroid, and it consists of approximately 3–5% of malign thyroid neoplasms. The most common presentation of sporadic MTC is solitary thyroid nodule (in 75–95% of patients). Unfortunately, most patients have metastatic disease at the time of diagnosis. The serum calcitonin concentrations usually correlate with tumor volume and reflect tumor differentiation. The fine-needle aspiration (FNA) biopsy is used for the diagnosis of MTC and its sensitivity is improved by the addition of immunohistochemical staining for calcitonin. Sporadic MTC accounts for approximately 75% of all cases of the disease, and the average age of presentation is in the fourth and sixth decades of life. Inherited MTC (in 25% of patients) is transmitted in an autosomal dominant fashion and emerges as a part of the multiple endocrine neoplasia type 2 (MEN2) syndrome which is divided into two different subgroups, MEN 2A and MEN 2B. Total thyroidectomy rather than unilateral lobectomy is the preferred surgical approach because especially inherited MTC tends to be a bilateral or multifocal disease. Additional cervical lymph node dissection is made according to the findings of pre/intraoperative ultrasound identification of lymph node metastases. The initial therapy for metastatic MTC patients depends on the presence of RET mutation and could be selective and non-selective TKIs (selpercatinib, cabozantinib, or vandetanib, etc.). However, sorafenib, sunitinib, or Lenvatinib, etc. are reasonable options for patients who fail first-line treatment.

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

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 229.99
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

References

  1. Noone A, Howlader N, Krapcho M, Miller D, Brest A, Yu M et al (2018) Surveillance, epidemiology, and end results (SEER) program cancer statistics review, 1975–2015. National Cancer Institute, Bethesda

    Google Scholar 

  2. Filetti S, Durante C, Hartl D, Leboulleux S, Locati L, Newbold K et al (2019) Thyroid cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 30(12):1856–1883

    Article  CAS  PubMed  Google Scholar 

  3. Siegel RL, Miller KD, Jemal A (2019) Cancer statistics, 2019. CA Cancer J Clin 69(1):7–34

    Article  PubMed  Google Scholar 

  4. Wells SA Jr, Asa SL, Dralle H, Elisei R, Evans DB, Gagel RF et al (2015) Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid 25(6):567–610

    Article  PubMed  PubMed Central  Google Scholar 

  5. Davies L, Welch HG (2006) Increasing incidence of thyroid cancer in the United States, 1973-2002. JAMA 295(18):2164–2167

    Article  CAS  PubMed  Google Scholar 

  6. Romei C, Elisei R, Pinchera A, Ceccherini I, Molinaro E, Mancusi F et al (1996) Somatic mutations of the ret protooncogene in sporadic medullary thyroid carcinoma are not restricted to exon 16 and are associated with tumor recurrence. J Clin Endocrinol Metab 81(4):1619–1622

    CAS  PubMed  Google Scholar 

  7. Hofstra RM, Landsvater RM, Ceccherini I, Stulp RP, Stelwagen T, Luo Y et al (1994) A mutation in the RET proto-oncogene associated with multiple endocrine neoplasia type 2B and sporadic medullary thyroid carcinoma. Nature 367(6461):375–376

    Article  CAS  PubMed  Google Scholar 

  8. Eng C, Mulligan LM, Smith DP, Healey CS, Frilling A, Raue F et al (1995) Low frequency of germline mutations in the RET proto-oncogene in patients with apparently sporadic medullary thyroid carcinoma. Clin Endocrinol 43(1):123–127

    Article  CAS  Google Scholar 

  9. Elisei R, Romei C, Cosci B, Agate L, Bottici V, Molinaro E et al (2007) RET genetic screening in patients with medullary thyroid cancer and their relatives: experience with 807 individuals at one center. J Clin Endocrinol Metab 92(12):4725–4729

    Article  CAS  PubMed  Google Scholar 

  10. Abe K, Adachi I, Miyakawa S, Tanaka M, Yamaguchi K, Tanaka N et al (1977) Production of calcitonin, adrenocorticotropic hormone, and beta-melanocyte-stimulating hormone in tumors derived from amine precursor uptake and decarboxylation cells. Cancer Res 37(11):4190–4194

    CAS  PubMed  Google Scholar 

  11. Baylin SB, Beaven MA, Engelman K, Sjoerdsma A (1970) Elevated histaminase activity in medullary carcinoma of the thyroid gland. N Engl J Med 283(23):1239–1244

    Article  CAS  PubMed  Google Scholar 

  12. Ishikawa N, Hamada S (1976) Association of medullary carcinoma of the thyroid with carcinoembryonic antigen. Br J Cancer 34(2):111–115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Takahashi M, Ritz J, Cooper GM (1985) Activation of a novel human transforming gene, ret, by DNA rearrangement. Cell 42(2):581–588

    Article  CAS  PubMed  Google Scholar 

  14. Ishizaka Y, Itoh F, Tahira T, Ikeda I, Sugimura T, Tucker J et al (1989) Human ret proto-oncogene mapped to chromosome 10q11.2. Oncogene 4(12):1519–1521

    CAS  PubMed  Google Scholar 

  15. F. American Thyroid Association Guidelines Task, Kloos RT, Eng C, Evans DB, Francis GL, Gagel RF et al (2009) Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid 19(6):565–612

    Article  Google Scholar 

  16. Elisei R, Cosci B, Romei C, Bottici V, Renzini G, Molinaro E et al (2008) Prognostic significance of somatic RET oncogene mutations in sporadic medullary thyroid cancer: a 10-year follow-up study. J Clin Endocrinol Metab 93(3):682–687

    Article  CAS  PubMed  Google Scholar 

  17. Moura MM, Cavaco BM, Pinto AE, Leite V (2011) High prevalence of RAS mutations in RET-negative sporadic medullary thyroid carcinomas. J Clin Endocrinol Metab 96(5):E863–E868

    Article  CAS  PubMed  Google Scholar 

  18. Ciampi R, Mian C, Fugazzola L, Cosci B, Romei C, Barollo S et al (2013) Evidence of a low prevalence of RAS mutations in a large medullary thyroid cancer series. Thyroid 23(1):50–57

    Article  CAS  PubMed  Google Scholar 

  19. Romei C, Ugolini C, Cosci B, Torregrossa L, Vivaldi A, Ciampi R et al (2012) Low prevalence of the somatic M918T RET mutation in micro-medullary thyroid cancer. Thyroid 22(5):476–481

    Article  CAS  PubMed  Google Scholar 

  20. Steiner AL, Goodman AD, Powers SR (1968) Study of a kindred with pheochromocytoma, medullary thyroid carcinoma, hyperparathyroidism and Cushing’s disease: multiple endocrine neoplasia, type 2. Medicine (Baltimore) 47(5):371–409

    Article  CAS  PubMed  Google Scholar 

  21. Schimke RN, Hartmann WH, Prout TE, Rimoin DL (1968) Syndrome of bilateral pheochromocytoma, medullary thyroid carcinoma and multiple neuromas. A possible regulatory defect in the differentiation of chromaffin tissue. N Engl J Med 279(1):1–7

    Article  CAS  PubMed  Google Scholar 

  22. Gorlin RJ, Sedano HO, Vickers RA, Cervenka J (1968) Multiple mucosal neuromas, pheochromocytoma and medullary carcinoma of the thyroid—a syndrome. Cancer 22(2):293–299. passim

    Article  CAS  PubMed  Google Scholar 

  23. Williams ED, Pollock DJ (1966) Multiple mucosal neuromata with endocrine tumours: a syndrome allied to von Recklinghausen’s disease. J Pathol Bacteriol 91(1):71–80

    Article  CAS  PubMed  Google Scholar 

  24. Oliveira MN, Hemerly JP, Bastos AU, Tamanaha R, Latini FR, Camacho CP et al (2011) The RET p.G533C mutation confers predisposition to multiple endocrine neoplasia type 2A in a Brazilian kindred and is able to induce a malignant phenotype in vitro and in vivo. Thyroid 21(9):975–985

    Article  CAS  PubMed  Google Scholar 

  25. Peppa M, Boutati E, Kamakari S, Pikounis V, Peros G, Panayiotides IG et al (2008) Multiple endocrine neoplasia type 2A in two families with the familial medullary thyroid carcinoma associated G533C mutation of the RET proto-oncogene. Eur J Endocrinol 159(6):767–771

    Article  CAS  PubMed  Google Scholar 

  26. Bethanis S, Koutsodontis G, Palouka T, Avgoustis C, Yannoukakos D, Bei T et al (2007) A newly detected mutation of the RET protooncogene in exon 8 as a cause of multiple endocrine neoplasia type 2A. Hormones (Athens) 6(2):152–156

    Article  PubMed  Google Scholar 

  27. Castro MR, Thomas BC, Richards ML, Zhang J, Morris JC (2013) Multiple endocrine neoplasia type 2A due to an exon 8 (G533C) mutation in a large North American kindred. Thyroid 23(12):1547–1552

    Article  CAS  PubMed  Google Scholar 

  28. Conzo G, Circelli L, Pasquali D, Sinisi A, Sabatino L, Accardo G et al (2012) Lessons to be learned from the clinical management of a MEN 2A patient bearing a novel 634/640/700 mutation of the RET proto-oncogene. Clin Endocrinol 77(6):934–936

    Article  CAS  Google Scholar 

  29. Raue F, Frank-Raue K (2012) Genotype-phenotype correlation in multiple endocrine neoplasia type 2. Clinics (Sao Paulo) 67(Suppl 1):69–75

    Article  PubMed  Google Scholar 

  30. Carlson KM, Dou S, Chi D, Scavarda N, Toshima K, Jackson CE et al (1994) Single missense mutation in the tyrosine kinase catalytic domain of the RET protooncogene is associated with multiple endocrine neoplasia type 2B. Proc Natl Acad Sci U S A 91(4):1579–1583

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Gimm O, Marsh DJ, Andrew SD, Frilling A, Dahia PL, Mulligan LM et al (1997) Germline dinucleotide mutation in codon 883 of the RET proto-oncogene in multiple endocrine neoplasia type 2B without codon 918 mutation. J Clin Endocrinol Metab 82(11):3902–3904

    Article  CAS  PubMed  Google Scholar 

  32. Rich TA, Feng L, Busaidy N, Cote GJ, Gagel RF, Hu M et al (2014) Prevalence by age and predictors of medullary thyroid cancer in patients with lower risk germline RET proto-oncogene mutations. Thyroid 24(7):1096–1106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Saad MF, Ordonez NG, Rashid RK, Guido JJ, Hill CS Jr, Hickey RC et al (1984) Medullary carcinoma of the thyroid. A study of the clinical features and prognostic factors in 161 patients. Medicine (Baltimore) 63(6):319–342

    Article  CAS  PubMed  Google Scholar 

  34. Kebebew E, Ituarte PH, Siperstein AE, Duh QY, Clark OH (2000) Medullary thyroid carcinoma: clinical characteristics, treatment, prognostic factors, and a comparison of staging systems. Cancer 88(5):1139–1148

    Article  CAS  PubMed  Google Scholar 

  35. Barbet J, Campion L, Kraeber-Bodere F, Chatal JF, G.T.E.S. Group (2005) Prognostic impact of serum calcitonin and carcinoembryonic antigen doubling-times in patients with medullary thyroid carcinoma. J Clin Endocrinol Metab 90(11):6077–6084

    Article  CAS  PubMed  Google Scholar 

  36. Trimboli P, Treglia G, Guidobaldi L, Romanelli F, Nigri G, Valabrega S et al (2015) Detection rate of FNA cytology in medullary thyroid carcinoma: a meta-analysis. Clin Endocrinol 82(2):280–285

    Article  Google Scholar 

  37. Bhanot P, Yang J, Schnadig VJ, Logrono R (2007) Role of FNA cytology and immunochemistry in the diagnosis and management of medullary thyroid carcinoma: report of six cases and review of the literature. Diagn Cytopathol 35(5):285–292

    Article  PubMed  Google Scholar 

  38. Khurana R, Agarwal A, Bajpai VK, Verma N, Sharma AK, Gupta RP et al (2004) Unraveling the amyloid associated with human medullary thyroid carcinoma. Endocrinology 145(12):5465–5470

    Article  CAS  PubMed  Google Scholar 

  39. Mendelsohn G, Wells SA Jr, Baylin SB (1984) Relationship of tissue carcinoembryonic antigen and calcitonin to tumor virulence in medullary thyroid carcinoma. An immunohistochemical study in early, localized, and virulent disseminated stages of disease. Cancer 54(4):657–662

    Article  CAS  PubMed  Google Scholar 

  40. Ibrahim M, Hammoud K, Maheshwari M, Pandya A (2011) Congenital cystic lesions of the head and neck. Neuroimaging Clin 21(3):621–639

    Article  Google Scholar 

  41. Abuabara A, Baratto Filho F, Fuzza RF (2010) Thyroglossal duct cyst. RSBO Revista Sul-Brasileira de Odontologia 7(2):244–246

    Google Scholar 

  42. Cătălina R, Alina O, Mioriţa T (2015) Compressing dermoid cyst of the neck. Ther Pharmacol Clin Toxicol 19(4)

    Google Scholar 

  43. April MM, Ward RF, Garelick JM (1998) Diagnosis, management, and follow-up of congenital head and neck teratomas. Laryngoscope 108(9):1398–1401

    Article  CAS  PubMed  Google Scholar 

  44. Leung AK, Davies HD (2009) Cervical lymphadenitis: etiology, diagnosis, and management. Curr Infect Dis Rep 11(3):183–189

    Article  PubMed  PubMed Central  Google Scholar 

  45. Schwetschenau E, Kelley DJ (2002) The adult neck mass. Am Fam Physician 66(5):831

    PubMed  Google Scholar 

  46. Steenbergh P, Höppener J, Zandberg J, Visser A, Lips C, Jansz H (1986) Structure and expression of the human calcitonin/CGRP genes. FEBS Lett 209(1):97–103

    Article  CAS  PubMed  Google Scholar 

  47. Whang KT, Steinwald PM, White JC, Nylen ES, Snider RH, Simon GL et al (1998) Serum calcitonin precursors in sepsis and systemic inflammation. J Clin Endocrinol Metabol 83(9):3296–3301

    CAS  Google Scholar 

  48. Kratzsch J, Petzold A, Raue F, Reinhardt W, Brocker-Preuss M, Gorges R et al (2011) Basal and stimulated calcitonin and procalcitonin by various assays in patients with and without medullary thyroid cancer. Clin Chem 57(3):467–474

    Article  CAS  PubMed  Google Scholar 

  49. Becker KL, Nylen ES, White JC, Muller B, Snider RH Jr (2004) Clinical review 167: procalcitonin and the calcitonin gene family of peptides in inflammation, infection, and sepsis: a journey from calcitonin back to its precursors. J Clin Endocrinol Metab 89(4):1512–1525

    Article  CAS  PubMed  Google Scholar 

  50. Guyetant S, Rousselet MC, Durigon M, Chappard D, Franc B, Guerin O et al (1997) Sex-related C cell hyperplasia in the normal human thyroid: a quantitative autopsy study. J Clin Endocrinol Metab 82(1):42–47

    Article  CAS  PubMed  Google Scholar 

  51. Basuyau JP, Mallet E, Leroy M, Brunelle P (2004) Reference intervals for serum calcitonin in men, women, and children. Clin Chem 50(10):1828–1830

    Article  CAS  PubMed  Google Scholar 

  52. Machens A, Dralle H (2010) Peak calcitonin cut-off levels for the diagnosis of occult medullary thyroid cancer: evidence of confounding by gender. Clin Endocrinol 73(2):274

    Article  Google Scholar 

  53. Scheuba C, Kaserer K, Moritz A, Drosten R, Vierhapper H, Bieglmayer C et al (2009) Sporadic hypercalcitoninemia: clinical and therapeutic consequences. Endocr Relat Cancer 16(1):243–253

    Article  CAS  PubMed  Google Scholar 

  54. Costante G, Meringolo D, Durante C, Bianchi D, Nocera M, Tumino S et al (2007) Predictive value of serum calcitonin levels for preoperative diagnosis of medullary thyroid carcinoma in a cohort of 5817 consecutive patients with thyroid nodules. J Clin Endocrinol Metab 92(2):450–455

    Article  CAS  PubMed  Google Scholar 

  55. Whang KT, Steinwald PM, White JC, Nylen ES, Snider RH, Simon GL et al (1998) Serum calcitonin precursors in sepsis and systemic inflammation. J Clin Endocrinol Metab 83(9):3296–3301

    CAS  PubMed  Google Scholar 

  56. Schuetz M, Duan H, Wahl K, Pirich C, Antoni A, Kommata S et al (2006) T lymphocyte cytokine production patterns in Hashimoto patients with elevated calcitonin levels and their relationship to tumor initiation. Anticancer Res 26(6B):4591–4596

    CAS  PubMed  Google Scholar 

  57. Machens A, Haedecke J, Holzhausen HJ, Thomusch O, Schneyer U, Dralle H (2000) Differential diagnosis of calcitonin-secreting neuroendocrine carcinoma of the foregut by pentagastrin stimulation. Langenbecks Arch Surg 385(6):398–401

    Article  CAS  PubMed  Google Scholar 

  58. Toledo SP, Lourenco DM Jr, Santos MA, Tavares MR, Toledo RA, Correia-Deur JE (2009) Hypercalcitoninemia is not pathognomonic of medullary thyroid carcinoma. Clinics (Sao Paulo) 64(7):699–706

    Article  PubMed  Google Scholar 

  59. Cohen EG, Shaha AR, Rinaldo A, Devaney KO, Ferlito A (2004) Medullary thyroid carcinoma. Acta Otolaryngol 124(5):544–557

    Article  PubMed  Google Scholar 

  60. Lee KB, Jang IM, Roh H, Ahn MY, Woo HY (2008) Transient urinary retention in acute right lateral medullary infarction. Neurologist 14(5):312–315

    Article  PubMed  Google Scholar 

  61. Mirallie E, Vuillez JP, Bardet S, Frampas E, Dupas B, Ferrer L et al (2005) High frequency of bone/bone marrow involvement in advanced medullary thyroid cancer. J Clin Endocrinol Metab 90(2):779–788

    Article  CAS  PubMed  Google Scholar 

  62. Oudoux A, Salaun PY, Bournaud C, Campion L, Ansquer C, Rousseau C et al (2007) Sensitivity and prognostic value of positron emission tomography with F-18-fluorodeoxyglucose and sensitivity of immunoscintigraphy in patients with medullary thyroid carcinoma treated with anticarcinoembryonic antigen-targeted radioimmunotherapy. J Clin Endocrinol Metab 92(12):4590–4597

    Article  CAS  PubMed  Google Scholar 

  63. Giraudet AL, Vanel D, Leboulleux S, Auperin A, Dromain C, Chami L et al (2007) Imaging medullary thyroid carcinoma with persistent elevated calcitonin levels. J Clin Endocrinol Metab 92(11):4185–4190

    Article  CAS  PubMed  Google Scholar 

  64. Ong SC, Schoder H, Patel SG, Tabangay-Lim IM, Doddamane I, Gonen M et al (2007) Diagnostic accuracy of 18F-FDG PET in restaging patients with medullary thyroid carcinoma and elevated calcitonin levels. J Nucl Med 48(4):501–507

    Article  CAS  PubMed  Google Scholar 

  65. Osamura RY, Yasuda O, Kawakami T, Itoh Y, Inada K, Kakudo K (1997) Immunoelectron microscopic demonstration of regulated pathway for calcitonin and constitutive pathway for carcinoembryonic antigen in the same cells of human medullary carcinomas of thyroid glands. Mod Pathol 10(1):7–11

    CAS  PubMed  Google Scholar 

  66. Wells SA Jr, Haagensen DE Jr, Linehan WM, Farrell RE, Dilley WG (1978) The detection of elevated plasma levels of carcinoembryonic antigen in patients with suspected or established medullary thyroid carcinoma. Cancer 42(3 Suppl):1498–1503

    Article  CAS  PubMed  Google Scholar 

  67. Rougier P, Calmettes C, Laplanche A, Travagli JP, Lefevre M, Parmentier C et al (1983) The values of calcitonin and carcinoembryonic antigen in the treatment and management of nonfamilial medullary thyroid carcinoma. Cancer 51(5):855–862

    Article  CAS  PubMed  Google Scholar 

  68. Machens A, Ukkat J, Hauptmann S, Dralle H (2007) Abnormal carcinoembryonic antigen levels and medullary thyroid cancer progression: a multivariate analysis. Arch Surg 142(3):289–293; discussion 294

    Article  CAS  PubMed  Google Scholar 

  69. Turkdogan S, Forest VI, Hier MP, Tamilia M, Florea A, Payne RJ (2018) Carcinoembryonic antigen levels correlated with advanced disease in medullary thyroid cancer. J Otolaryngol Head Neck Surg 47(1):55

    Article  PubMed  PubMed Central  Google Scholar 

  70. Wells SA Jr, Gosnell JE, Gagel RF, Moley J, Pfister D, Sosa JA et al (2010) Vandetanib for the treatment of patients with locally advanced or metastatic hereditary medullary thyroid cancer. J Clin Oncol 28(5):767–772

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Machens A, Dralle H (2015) Surgical treatment of medullary thyroid cancer. Recent Results Cancer Res 204:187–205

    Article  PubMed  Google Scholar 

  72. Brierley J, Tsang R, Simpson WJ, Gospodarowicz M, Sutcliffe S, Panzarella T (1996) Medullary thyroid cancer: analyses of survival and prognostic factors and the role of radiation therapy in local control. Thyroid 6(4):305–310

    Article  CAS  PubMed  Google Scholar 

  73. Wu LT, Averbuch SD, Ball DW, de Bustros A, Baylin SB, McGuire WP III (1994) Treatment of advanced medullary thyroid carcinoma with a combination of cyclophosphamide, vincristine, and dacarbazine. Cancer 73(2):432–436

    Article  CAS  PubMed  Google Scholar 

  74. Nocera M, Baudin E, Pellegriti G, Cailleux AF, Mechelany-Corone C, Schlumberger M (2000) Treatment of advanced medullary thyroid cancer with an alternating combination of doxorubicin-streptozocin and 5 FU-dacarbazine. Groupe d’Etude des Tumeurs a Calcitonine (GETC). Br J Cancer 83(6):715–718

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Shimaoka K, Schoenfeld DA, DeWys WD, Creech RH, DeConti R (1985) A randomized trial of doxorubicin versus doxorubicin plus cisplatin in patients with advanced thyroid carcinoma. Cancer 56(9):2155–2160

    Article  CAS  PubMed  Google Scholar 

  76. Kloos RT, Eng C, Evans DB, Francis GL, Gagel RF, Gharib H et al (2009) Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid 19(6):565–612

    Article  PubMed  Google Scholar 

  77. Machens A, Dralle H (2010) Biomarker-based risk stratification for previously untreated medullary thyroid cancer. J Clin Endocrinol Metab 95(6):2655–2663

    Article  CAS  PubMed  Google Scholar 

  78. Yip DT, Hassan M, Pazaitou-Panayiotou K, Ruan DT, Gawande AA, Gaz RD et al (2011) Preoperative basal calcitonin and tumor stage correlate with postoperative calcitonin normalization in patients undergoing initial surgical management of medullary thyroid carcinoma. Surgery 150(6):1168–1177

    Article  PubMed  Google Scholar 

  79. Samaan NA, Schultz PN, Hickey RC (1988) Medullary thyroid carcinoma: prognosis of familial versus sporadic disease and the role of radiotherapy. J Clin Endocrinol Metab 67(4):801–805

    Article  CAS  PubMed  Google Scholar 

  80. Jimenez-Fonseca P, Carmona-Bayonas A, Font C, Plasencia-Martinez J, Calvo-Temprano D, Otero R et al (2018) The prognostic impact of additional intrathoracic findings in patients with cancer-related pulmonary embolism. Clin Transl Oncol 20(2):230–242

    Article  CAS  PubMed  Google Scholar 

  81. Esik O, Tusnady G, Tron L, Boer A, Szentirmay Z, Szabolcs I et al (2002) Markov model-based estimation of individual survival probability for medullary thyroid cancer patients. Pathol Oncol Res 8(2):93–104

    Article  PubMed  Google Scholar 

  82. Fife KM, Bower M, Harmer CL (1996) Medullary thyroid cancer: the role of radiotherapy in local control. Eur J Surg Oncol 22(6):588–591

    Article  CAS  PubMed  Google Scholar 

  83. Stankovic V, Borojevic N, Dzodic R, Golubicic I (2003) [Medullary carcinoma of the thyroid gland: effect of postoperative transcutaneous radiotherapy on local control and results of treatment]. Acta Chir Iugosl 50(3):125–130

    Google Scholar 

  84. Rowell NP (2019) The role of external beam radiotherapy in the management of medullary carcinoma of the thyroid: a systematic review. Radiother Oncol 136:113–120

    Article  CAS  PubMed  Google Scholar 

  85. Orlandi F, Caraci P, Berruti A, Puligheddu B, Pivano G, Dogliotti L et al (1994) Chemotherapy with dacarbazine and 5-fluorouracil in advanced medullary thyroid cancer. Ann Oncol 5(8):763–765

    Article  CAS  PubMed  Google Scholar 

  86. Petursson SR (1988) Metastatic medullary thyroid carcinoma. Complete response to combination chemotherapy with dacarbazine and 5-fluorouracil. Cancer 62(9):1899–1903

    Article  CAS  PubMed  Google Scholar 

  87. Gottlieb JA, Hill CS Jr (1974) Chemotherapy of thyroid cancer with adriamycin. Experience with 30 patients. N Engl J Med 290(4):193–197

    Article  CAS  PubMed  Google Scholar 

  88. Droz JP, Rougier P, Goddefroy V, Schlumberger M, Gardet P, Parmentier C (1984) [Chemotherapy for medullary cancer of the thyroid. Phase II trials with adriamycin and cis-platinum administered as monochemotherapy]. Bull Cancer 71(3):195–199

    Google Scholar 

  89. De Besi P, Busnardo B, Toso S, Girelli ME, Nacamulli D, Simioni N et al (1991) Combined chemotherapy with bleomycin, adriamycin, and platinum in advanced thyroid cancer. J Endocrinol Investig 14(6):475–480

    Article  Google Scholar 

  90. Deutschbein T, Matuszczyk A, Moeller LC, Unger N, Yuece A, Lahner H et al (2011) Treatment of advanced medullary thyroid carcinoma with a combination of cyclophosphamide, vincristine, and dacarbazine: a single-center experience. Exp Clin Endocrinol Diabetes 119(9):540–543

    Article  CAS  PubMed  Google Scholar 

  91. Schlumberger M, Abdelmoumene N, Delisle MJ, Couette JE (1995) Treatment of advanced medullary thyroid cancer with an alternating combination of 5 FU-streptozocin and 5 FU-dacarbazine. The Groupe d’Etude des Tumeurs a Calcitonine (GETC). Br J Cancer 71(2):363–365

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Gilliam LK, Kohn AD, Lalani T, Swanson PE, Vasko V, Patel A et al (2006) Capecitabine therapy for refractory metastatic thyroid carcinoma: a case series. Thyroid 16(8):801–810

    Article  CAS  PubMed  Google Scholar 

  93. Lacin S, Esin E, Karakas Y, Yalcin S (2015) Metastatic medullary thyroid cancer: a dramatic response to a systemic chemotherapy (temozolomide and capecitabine) regimen. Onco Targets Ther 8:1039–1042

    PubMed  PubMed Central  Google Scholar 

  94. Paiva CE, Michelin OC (2008) Use of capecitabine in refractory metastatic medullary thyroid carcinoma. Thyroid 18(5):587

    Article  PubMed  Google Scholar 

  95. Boichard A, Croux L, Al Ghuzlan A, Broutin S, Dupuy C, Leboulleux S et al (2012) Somatic RAS mutations occur in a large proportion of sporadic RET-negative medullary thyroid carcinomas and extend to a previously unidentified exon. J Clin Endocrinol Metab 97(10):E2031–E2035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Drilon A, Oxnard G, Wirth L, Besse B, Gautschi O, Tan S et al (2019) PL02.08 registrational results of LIBRETTO-001: a phase 1/2 trial of LOXO-292 in patients with RET fusion-positive lung cancers. J Thorac Oncol 14(10):S6–S7

    Article  Google Scholar 

  97. Wells SA Jr, Robinson BG, Gagel RF, Dralle H, Fagin JA, Santoro M et al (2012) Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol 30(2):134–141

    Article  CAS  PubMed  Google Scholar 

  98. Schlumberger M, Elisei R, Muller S, Schoffski P, Brose M, Shah M et al (2017) Overall survival analysis of EXAM, a phase III trial of cabozantinib in patients with radiographically progressive medullary thyroid carcinoma. Ann Oncol 28(11):2813–2819

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Lam ET, Ringel MD, Kloos RT, Prior TW, Knopp MV, Liang J et al (2010) Phase II clinical trial of sorafenib in metastatic medullary thyroid cancer. J Clin Oncol 28(14):2323–2330

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Carr LL, Mankoff DA, Goulart BH, Eaton KD, Capell PT, Kell EM et al (2010) 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 16(21):5260–5268

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Bible KC, Suman VJ, Molina JR, Smallridge RC, Maples WJ, Menefee ME et al (2014) A multicenter phase 2 trial of pazopanib in metastatic and progressive medullary thyroid carcinoma: MC057H. J Clin Endocrinol Metab 99(5):1687–1693

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Schlumberger M, Jarzab B, Cabanillas ME, Robinson B, Pacini F, Ball DW et al (2016) A phase II trial of the multitargeted tyrosine kinase inhibitor lenvatinib (E7080) in advanced medullary thyroid cancer. Clin Cancer Res 22(1):44–53

    Article  CAS  PubMed  Google Scholar 

  103. Schlumberger MJ, Elisei R, Bastholt L, Wirth LJ, Martins RG, Locati LD et al (2009) Phase II study of safety and efficacy of motesanib in patients with progressive or symptomatic, advanced or metastatic medullary thyroid cancer. J Clin Oncol 27(23):3794–3801

    Article  CAS  PubMed  Google Scholar 

  104. Cohen EE, Rosen LS, Vokes EE, Kies MS, Forastiere AA, Worden FP et al (2008) Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II study. J Clin Oncol 26(29):4708–4713

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. de Groot JW, Zonnenberg BA, van Ufford-Mannesse PQ, de Vries MM, Links TP, Lips CJ et al (2007) A phase II trial of imatinib therapy for metastatic medullary thyroid carcinoma. J Clin Endocrinol Metab 92(9):3466–3469

    Article  PubMed  Google Scholar 

  106. Wirth LJ, Sherman E, Robinson B, Solomon B, Kang H, Lorch J et al (2020) Efficacy of Selpercatinib in RET-altered thyroid cancers. N Engl J Med 383(9):825–835

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Carlomagno F, Vitagliano D, Guida T, Ciardiello F, Tortora G, Vecchio G et al (2002) ZD6474, an orally available inhibitor of KDR tyrosine kinase activity, efficiently blocks oncogenic RET kinases. Cancer Res 62(24):7284–7290

    CAS  PubMed  Google Scholar 

  108. Yakes FM, Chen J, Tan J, Yamaguchi K, Shi Y, Yu P et al (2011) Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Mol Cancer Ther 10(12):2298–2308

    Article  CAS  PubMed  Google Scholar 

  109. Sennino B, Naylor RM, Tabruyn SP, You WK, Aftab DT, McDonald DM (2009) Abstract A13: reduction of tumor invasiveness and metastasis and prolongation of survival of RIP-Tag2 mice after inhibition of VEGFR plus c-met by XL184. AACR 8:A13

    Google Scholar 

  110. Kurzrock R, Sherman SI, Ball DW, Forastiere AA, Cohen RB, Mehra R et al (2011) Activity of XL184 (Cabozantinib), an oral tyrosine kinase inhibitor, in patients with medullary thyroid cancer. J Clin Oncol 29(19):2660–2666

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Wilhelm SM, Carter C, Tang L, Wilkie D, McNabola A, Rong H et al (2004) BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 64(19):7099–7109

    Article  CAS  PubMed  Google Scholar 

  112. Frank-Raue K, Ganten M, Kreissl MC, Raue F (2011) Rapid response to sorafenib in metastatic medullary thyroid carcinoma. Exp Clin Endocrinol Diabetes 119(3):151–155

    Article  CAS  PubMed  Google Scholar 

  113. Benekli M, Yalcin S, Ozkan M, Elkiran ET, Sevinc A, Cabuk D et al (2015) Efficacy of sorafenib in advanced differentiated and medullary thyroid cancer: experience in a Turkish population. Onco Targets Ther 8:1–5

    PubMed  Google Scholar 

  114. Kocsis J, Szekanecz E, Bassam A, Uhlyarik A, Papai Z, Rubovszky G et al (2019) First line sorafenib treatment for metastatic medullary thyroid cancer: efficacy and safety analysis. Exp Clin Endocrinol Diabetes 127(4):240–246

    Article  CAS  PubMed  Google Scholar 

  115. Mendel DB, Laird AD, Xin X, Louie SG, Christensen JG, Li G et al (2003) In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res 9(1):327–337

    CAS  PubMed  Google Scholar 

  116. Kumar R, Knick VB, Rudolph SK, Johnson JH, Crosby RM, Crouthamel MC et al (2007) Pharmacokinetic-pharmacodynamic correlation from mouse to human with pazopanib, a multikinase angiogenesis inhibitor with potent antitumor and antiangiogenic activity. Mol Cancer Ther 6(7):2012–2021

    Article  CAS  PubMed  Google Scholar 

  117. Hu-Lowe DD, Zou HY, Grazzini ML, Hallin ME, Wickman GR, Amundson K et al (2008) Nonclinical antiangiogenesis and antitumor activities of axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor receptor tyrosine kinases 1, 2, 3. Clin Cancer Res 14(22):7272–7283

    Article  CAS  PubMed  Google Scholar 

  118. Capdevila J, Trigo JM, Aller J, Manzano JL, Adrian SG, Llopis CZ et al (2017) Axitinib treatment in advanced RAI-resistant differentiated thyroid cancer (DTC) and refractory medullary thyroid cancer (MTC). Eur J Endocrinol 177(4):309–317

    Article  CAS  PubMed  Google Scholar 

  119. Matsui J, Yamamoto Y, Funahashi Y, Tsuruoka A, Watanabe T, Wakabayashi T et al (2008) E7080, a novel inhibitor that targets multiple kinases, has potent antitumor activities against stem cell factor producing human small cell lung cancer H146, based on angiogenesis inhibition. Int J Cancer 122(3):664–671

    Article  CAS  PubMed  Google Scholar 

  120. Tohyama O, Matsui J, Kodama K, Hata-Sugi N, Kimura T, Okamoto K et al (2014) Antitumor activity of lenvatinib (e7080): an angiogenesis inhibitor that targets multiple receptor tyrosine kinases in preclinical human thyroid cancer models. J Thyroid Res 2014:638747

    Article  PubMed  PubMed Central  Google Scholar 

  121. Boss DS, Glen H, Beijnen JH, Keesen M, Morrison R, Tait B et al (2012) A phase I study of E7080, a multitargeted tyrosine kinase inhibitor, in patients with advanced solid tumours. Br J Cancer 106(10):1598–1604

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Matsui J, Minoshima Y, Tsuruoka A, Funahashi Y (2010) Multi-targeted kinase inhibitor E7080 showed anti-tumor activity against medullary thyroid carcinoma and squamous thyroid carcinoma cell line based on RET and VEGFR2 tyrosine kinase inhibition. AACR 70:3614

    Google Scholar 

  123. Brose MS, Bible KC, Chow LQM, Gilbert J, Grande C, Worden F et al (2018) Management of treatment-related toxicities in advanced medullary thyroid cancer. Cancer Treat Rev 66:64–73

    Article  CAS  PubMed  Google Scholar 

  124. Subbiah V, Velcheti V, Tuch BB, Ebata K, Busaidy NL, Cabanillas ME et al (2018) Selective RET kinase inhibition for patients with RET-altered cancers. Ann Oncol 29(8):1869–1876

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Oncology, Yeditepe University Faculty of Medicine, Istanbul, Turkey

    Şahin Laçin

  2. Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Turkey

    Suayib Yalcin

Authors
  1. Şahin Laçin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Suayib Yalcin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Suayib Yalcin .

Editor information

Editors and Affiliations

  1. Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Türkiye

    Suayib Yalcin

  2. Retired, Department of Endocrine Oncology, Uppsala University Hospital, Uppsala, Sweden

    Kjell Öberg

Rights and permissions

Reprints and permissions

Copyright information

© 2024 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Laçin, Ş., Yalcin, S. (2024). Medullary Thyroid Cancer. In: Yalcin, S., Öberg, K. (eds) Neuroendocrine Tumours. Springer, Cham. https://doi.org/10.1007/978-3-031-56968-5_23

Download citation

  • DOI: https://doi.org/10.1007/978-3-031-56968-5_23

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-031-56967-8

  • Online ISBN: 978-3-031-56968-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation