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Aggressive medullary thyroid cancer, an analysis of the Irish National Cancer Registry

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Irish Journal of Medical Science (1971 -) Aims and scope Submit manuscript

Abstract

Background and objectives

Medullary thyroid cancer consists of a spectrum of disease that ranges from extremely indolent tumors to aggressive types associated with a high mortality rate. The objective of our study is to evaluate the prognostic factors and outcomes of patients diagnosed with MTC in a homogenous population, and to examine patients diagnosed with MTC for mutations in the RET proto-oncogene from the same period.

Methods

A retrospective analysis of the National Cancer Registry in Ireland was undertaken, between 1998 and 2007. The Kaplan–Meier method was used to determine overall survival and factors predictive of outcome were determined by univariate and multivariate analysis by cox regression using Stata 13 software.

Main findings

Forty-three patients were diagnosed with medullary thyroid cancer, 55.8 % were female and 44.2 % were male. A median age of 52 was found. The overall median survival was 6.32 years and the 1- and 5-year overall survival was 88.37 and 62.79 %, respectively, with 10-year survival calculated at 48.63 %. On univariate analysis age, stage and surgical intervention were statistically significant indicators of prognosis. T stage and age remained statistically significant indicators of prognosis on multivariate analysis. Two patients with no history of MEN syndromes or family history of medullary thyroid cancer had RET proto-onocogene mutations.

Conclusions

Our patient cohort was substantially older and presented at an advanced T status than what is commonly seen in the literature. This may account for poor survival outcomes and the very low pick-up of RET mutations in sporadic medullary thyroid cancer.

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References

  1. Krampitz GW, Norton JA (2014) RET gene mutations (genotype and phenotype) of multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma. Cancer 120:1920–1931

    Article  CAS  PubMed  Google Scholar 

  2. Hundahl SA, Fleming ID, Fremgen AM, Menck HR (1998) A national cancer data base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985–1995 (see commetns). Cancer 83:2638–2648

    Article  CAS  PubMed  Google Scholar 

  3. 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 88:1139–1148

    Article  CAS  PubMed  Google Scholar 

  4. Chen H, Sippel RS, O’Dorisio MS et al (2010) The North American Neuroendocrine Tumor Society consensus guideline for the diagnosis and management of neuroendocrine tumors: pheochromocytoma, paraganglioma, and medullary thyroid cancer. Pancreas 39:775–783

    Article  PubMed  PubMed Central  Google Scholar 

  5. O’Brien K, Comber H, Sharp L (2014) Completeness of case ascertainment at the Irish National Cancer Registry. Ir J Med Sci 183:219–224

    Article  PubMed  Google Scholar 

  6. National Cancer Registry Ireland. Available at: http://www.ncri.ie/. Accessed 18 Sep 2014

  7. Stata. Stata 13. Available at: http://www.stata.com/stata13/. Accessed 16 Jul 2014

  8. National Centre for Medical Genetics. Available at: http://www.genetics.ie/. Accessed 09 Oct 2014

  9. Central Statistics Office I. Population 1901–2011. Available at: http://www.cso.ie/Quicktables/GetQuickTables.aspx?FileName=CNA13.asp&TableName=Population+1901+-+2011&StatisticalProduct=DB_CN. Accessed 17 Jul 2014

  10. Perros P, Boelaert K, Colley S et al (2014) Guidelines for the management of thyroid cancer. Clin Endocrinol 81(Suppl 1):1–122

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  12. Clark JR, Fridman TR, Odell MJ, Brierley J, Walfish PG, Freeman JL (2005) Prognostic variables and calcitonin in medullary thyroid cancer. Laryngoscope 115:1445–1450

    Article  CAS  PubMed  Google Scholar 

  13. Cupisti K, Wolf A, Raffel A et al (2007) Long-term clinical and biochemical follow-up in medullary thyroid carcinoma: a single institution’s experience over 20 years. Ann Surg 246:815–821

    Article  PubMed  Google Scholar 

  14. de Groot JW, Plukker JT, Wolffenbuttel BH, Wiggers T, Sluiter WJ, Links TP (2006) Determinants of life expectancy in medullary thyroid cancer: age does not matter. Clin Endocrinol 65:729–736

    Article  Google Scholar 

  15. Hyer SL, Vini L, A’Hern R, Harmer C (2000) Medullary thyroid cancer: multivariate analysis of prognostic factors influencing survival. Eur J Surg Oncol J Eur Soc Surg Oncol Br Assoc Surg Oncol 26:686–690

    CAS  Google Scholar 

  16. Pelizzo MR, Boschin IM, Bernante P et al (2007) Natural history, diagnosis, treatment and outcome of medullary thyroid cancer: 37 years experience on 157 patients. Eur J Surg Oncol J Eur Soc Surg Oncol Br Assoc Surg Oncol 33:493–497

    CAS  Google Scholar 

  17. Rendl G, Manzl M, Hitzl W, Sungler P, Pirich C (2008) Long-term prognosis of medullary thyroid carcinoma. Clin Endocrinol 69:497–505

    Article  CAS  Google Scholar 

  18. Rios A, Rodriguez JM, Acosta JM et al (2010) Prognostic value of histological and immunohistochemical characteristics for predicting the recurrence of medullary thyroid carcinoma. Ann Surg Oncol 17:2444–2451

    Article  CAS  PubMed  Google Scholar 

  19. Saad MF, Ordonez NG, Rashid RK et al (1984) Medullary carcinoma of the thyroid. A study of the clinical features and prognostic factors in 161 patients. Medicine 63:319–342

    Article  CAS  PubMed  Google Scholar 

  20. Bergholm U, Adami HO, Bergstrom R, Backdahl M, Akerstrom G (1990) Long-term survival in sporadic and familial medullary thyroid carcinoma with special reference to clinical characteristics as prognostic factors. The Swedish MTC Study Group. Acta Chir Scand 156:37–46

    CAS  PubMed  Google Scholar 

  21. Kandil E, Gilson MM, Alabbas HH, Tufaro AP, Dackiw A, Tufano RP (2011) Survival implications of cervical lymphadenectomy in patients with medullary thyroid cancer. Ann Surg Oncol 18:1028–1034

    Article  PubMed  Google Scholar 

  22. Modigliani E, Cohen R, Campos JM et al (1998) Prognostic factors for survival and for biochemical cure in medullary thyroid carcinoma: results in 899 patients. The GETC Study Group. Groupe d’etude des tumeurs a calcitonine. Clin Endocrinol 48:265–273

    Article  CAS  Google Scholar 

  23. Roman S, Lin R, Sosa JA (2006) Prognosis of medullary thyroid carcinoma: demographic, clinical, and pathologic predictors of survival in 1252 cases. Cancer 107:2134–2142

    Article  PubMed  Google Scholar 

  24. Dottorini ME, Assi A, Sironi M, Sangalli G, Spreafico G, Colombo L (1996) Multivariate analysis of patients with medullary thyroid carcinoma. Prognostic significance and impact on treatment of clinical and pathologic variables. Cancer 77:1556–1565

    Article  CAS  PubMed  Google Scholar 

  25. Elisei R, Cosci B, Romei C 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 93:682–687

    Article  CAS  PubMed  Google Scholar 

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

    CAS  Google Scholar 

  27. Esfandiari NH, Hughes DT, Yin H, Banerjee M, Haymart MR (2014) The Effect of extent of surgery and number of lymph node metastases on overall survival in patients with medullary thyroid cancer. J Clin Endocrinol Metab 99:448–454

    Article  CAS  PubMed  Google Scholar 

  28. Balentine CJ, Chen H (2015) Chasing calcitonin: reoperations for medullary thyroid carcinoma. Ann Surg Oncol 22:7–8

    Article  PubMed  Google Scholar 

  29. American Thyroid Association Guidelines Task F, Kloos RT, Eng C et al (2009) Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid Off J Am Thyroid Assoc 19:565–612

    Article  Google Scholar 

  30. Moley JF, DeBenedetti MK (1999) Patterns of nodal metastases in palpable medullary thyroid carcinoma: recommendations for extent of node dissection. Ann Surg 229:880–887 (discussion 887–888)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Oskam IM, Hoebers F, Balm AJ et al (2008) Neck management in medullary thyroid carcinoma. Eur J Surg Oncol J Eur Soc Surg Oncol Br Assoc Surg Oncol 34:71–76

    CAS  Google Scholar 

  32. Weber T, Schilling T, Frank-Raue K et al (2001) Impact of modified radical neck dissection on biochemical cure in medullary thyroid carcinomas. Surgery 130:1044–1049

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  34. Emmertsen K (1985) Medullary thyroid carcinoma and calcitonin. Dan Med Bull 32:1–28

    CAS  PubMed  Google Scholar 

  35. Ukkat J, Gimm O, Brauckhoff M, Bilkenroth U, Dralle H (2004) Single center experience in primary surgery for medullary thyroid carcinoma. World J Surg 28:1271–1274

    Article  PubMed  Google Scholar 

  36. Rowland KJ, Jin LX, Moley JF (2015) Biochemical cure after reoperations for medullary thyroid carcinoma: a meta-analysis. Ann Surg Oncol 22:96–102

    Article  PubMed  Google Scholar 

  37. Fersht N, Vini L, A’Hern R, Harmer C (2001) The role of radiotherapy in the management of elevated calcitonin after surgery for medullary thyroid cancer. Thyroid Off J Am Thyroid Assoc 11:1161–1168

    Article  CAS  Google Scholar 

  38. Schwartz DL, Rana V, Shaw S et al (2008) Postoperative radiotherapy for advanced medullary thyroid cancer–local disease control in the modern era. Head Neck 30:883–888

    Article  PubMed  Google Scholar 

  39. 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 Off J Am Thyroid Assoc 6:305–310

    Article  CAS  Google Scholar 

  40. Santoro M, Rosati R, Grieco M et al (1990) The ret proto-oncogene is consistently expressed in human pheochromocytomas and thyroid medullary carcinomas. Oncogene 5:1595–1598

    CAS  PubMed  Google Scholar 

  41. Herrmann ME, Talpos GB, Mohamed AN et al (1991) Genetic markers in thyroid tumors. Surgery 110:941–947 (discussion 947–948)

    CAS  PubMed  Google Scholar 

  42. Eng C, Smith DP, Mulligan LM et al (1994) Point mutation within the tyrosine kinase domain of the RET proto-oncogene in multiple endocrine neoplasia type 2B and related sporadic tumours. Hum Mol Genet 3:237–241

    Article  CAS  PubMed  Google Scholar 

  43. Perri F, Pezzullo L, Chiofalo MG et al (2014) Targeted therapy: a new hope for thyroid carcinomas. Crit Rev Oncol Hematol 94(1):55–63

    Article  PubMed  Google Scholar 

  44. Santoro M, Carlomagno F, Romano A et al (1995) Activation of RET as a dominant transforming gene by germline mutations of MEN2A and MEN2B. Science 267:381–383

    Article  CAS  PubMed  Google Scholar 

  45. Dvorakova S, Vaclavikova E, Sykorova V et al (2008) Somatic mutations in the RET proto-oncogene in sporadic medullary thyroid carcinomas. Mol Cell Endocrinol 284:21–27

    Article  CAS  PubMed  Google Scholar 

  46. Marsh DJ, Learoyd DL, Andrew SD et al (1996) Somatic mutations in the RET proto-oncogene in sporadic medullary thyroid carcinoma. Clin Endocrinol 44:249–257

    Article  CAS  Google Scholar 

  47. FDA. Vandetanib is first drug approved for medullary thyroid cancer. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm250168.htm. Accessed 14 Jan 2015

  48. Wells SA Jr, Robinson BG, Gagel RF et al (2012) Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol Off J Am Soc Clin Oncol 30:134–141

    Article  CAS  Google Scholar 

  49. Elisei R, Schlumberger MJ, Muller SP et al (2013) Cabozantinib in progressive medullary thyroid cancer. J Clin Oncol Off J Am Soc Clin Oncol 31:3639–3646

    Article  CAS  Google Scholar 

  50. Simbolo M, Mian C, Barollo S et al (2014) High-throughput mutation profiling improves diagnostic stratification of sporadic medullary thyroid carcinomas. Virchows Arch Int J Pathol 465:73–78

    Article  CAS  Google Scholar 

  51. Brandi ML, Gagel RF, Angeli A et al (2001) Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab 86:5658–5671

    Article  CAS  PubMed  Google Scholar 

  52. Bairead E, Harmon DL, Curtis AM et al (2003) Association of NOD2 with Crohn’s disease in a homogenous Irish population. Eur J Hum Genet EJHG 11:237–244

    Article  CAS  PubMed  Google Scholar 

  53. Dunne C, Crowley J, Hagan R, Rooney G, Lawlor E (2008) HLA-A, B, Cw, DRB1, DQB1 and DPB1 alleles and haplotypes in the genetically homogenous Irish population. Int J Immunogenet 35:295–302

    Article  CAS  PubMed  Google Scholar 

  54. Tian C, Plenge RM, Ransom M et al (2008) Analysis and application of European genetic substructure using 300 K SNP information. PLoS Genet 4:e4

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Otolaryngology, Head and Neck Surgery, St. James’s Hospital, Dublin 8, Ireland

    P. Lennon, J. Kinsella & C. Timon

  2. National Cancer Register, Ireland, Cork, Ireland

    S. Deady

  3. Department of Clinical Genetics, Our Lady’s Children’s Hospital, Crumlin, Ireland

    N. White, D. Lambert & A. Green

  4. Department of Endocrinology, St. James’s Hospital, Dublin 8, Ireland

    M. L. Healy

  5. Department of Otolaryngology, Head and Neck Surgery, Beaumont Hospital, Dublin, Ireland

    J. P. O’ Neill

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  1. P. Lennon
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Correspondence to P. Lennon.

Ethics declarations

No funding was required or sought for this project. The authors declare no conflict of interest. The use of this anonymized data for research is covered by the Statutory Instrument, which established the Registry Board in 1991, and therefore no further ethical approval was sought.

Financial disclosure

We declare that there was no financial support or funding for this submission, and no sponsors.

Conflict of interest

We declare that there were no financial or personal relationships with other people or organizations that could inappropriately influence or bias the authors’ actions.

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Lennon, P., Deady, S., White, N. et al. Aggressive medullary thyroid cancer, an analysis of the Irish National Cancer Registry. Ir J Med Sci 186, 89–95 (2017). https://doi.org/10.1007/s11845-016-1455-1

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