Уважаемые пользователи!

Данный сайт содержит информацию для людей с медицинским образованием и специалистов здравоохранения.
Входя на сайт, Вы подтверждаете свое согласие с Условиями использования и Политикой конфиденциальности.

Dear visitor!
This site contains medical information for healthcare professionals.
You can go further, if you agree with Terms and Conditions and Privacy Policy on this site.

2012 European Thyroid Association Guidelines for Metastatic Medullary Thyroid Cancer

Cover Page


Distant metastases are the main cause of death in patients with medullary thyroid cancer (MTC). These 21 recommendations focus on MTC patients with distant metastases and a detailed followup protocol of patients with biochemical or imaging evidence of disease, selection criteria for treatment, and treatment modalities, including local and systemic treatments based on the results of recent trials. Asymptomatic patients with low tumor burden and stable disease may benefit from local treatment modalities and can be followed up at regular intervals of time. Imaging is usually performed every 6–12 months, or at longer inter vals of time depending on the doubling times of serum calcitonin and carcinoembryonic antigen levels. Patients with symptoms, large tumor burden and progression on imaging should receive systemic treatment. Indeed, major progress has recently been achieved with novel targeted therapies using kinase inhibitors directed against RET and VEGFR, but further research is needed to improve the outcome of these patients.

V V Voskoboynikov

D G Bel'tsevich

Email: beltsevich@rambler.ru

V E Vanushko

  1. M. Schlumbergera, L. Bastholtb, H. Drallec, B. Jarzabd. 2012 European Thyroid Association Guidelines for Metastatic Medullary Thyroid Cancer F. Pacinie, J.W.A. Smitf The European Thyroid Association Task Force
  2. Kloos R.T., Eng C., Evans D.B. et al. Medullary thyroid can cer: management guidelines of the American Thyroid Association. Thyroid. 2009; 19: 565–612.
  3. Atkins D., Eccles M., Flottorp S. et al. GRADE Working Group: Grading quality of evidence and strength of recommenda tions. BMC Health Serv. Res. 2004; 22 (4): 38.
  4. Swiglo B.A., Murad M.H., Schünemann H.J. et al. A case for clarity, consistency, and helpfulness: stateoftheart clinical practice guidelines in endocrinology using the grading of re commendations, assessment, development, and evaluation system. J. Clin. Endocrinol. Metab. 2008; 93: 666–673.
  5. Guyatt G., Gutterman D., Baumann M.H. et al. Grading strength of recommendations and quality of evidence in clinical guidelines: report from an American College of Chest Physicians task force. Chest. 2006; 129: 174–181.
  6. Schlumberger M., Carlomagno F., Baudin E. et al. New the rapeutic approaches to treat medullary thyroid carcinoma. Nat. Clin. Pract. Endocrinol. Metab. 2008; 4: 22–32.
  7. Giraudet A.L., Vanel D., Leboulleux S. et al. Imaging medul lary thyroid carcinoma with persistent elevated calcitonin le vels. J. Clin. Endocrinol. Metab. 2007; 92: 4185–4190.
  8. van Heerden J.A., Grant C.S., Gharib H. et al. Longterm course of patients with persistent hypercalcitoninemia after apparent curative primary surgery for medullary thyroid carci noma. Ann. Surg. 1990; 212: 395–400, discussion 400–401.
  9. Pellegriti G., Leboulleux S., Baudin E. et al. Longterm out come of medullary thyroid carcinoma in patients with normal postoperative medical imaging. Br. J. Cancer. 2003; 88: 1537–1542.
  10. Fialkowski E., Debenedetti M., Moley J. Longterm outcome of reoperations for medullary thyroid carcinoma. Wld J. Surg. 2008; 32: 754–765.
  11. Saad M.F., Fritsche H.A. Jr., Samaan N.A. Diagnostic and prognostic values of carcinoembryonic antigen in medullary carcinoma of the thyroid. J. Clin. Endocrinol. Metab. 1984; 58: 889–894.
  12. Miyauchi A., Onishi T., Morimoto S. et al. Relation of doubling time of plasma calcitonin levels to prognosis and recurrence of medullary thyroid carcinoma. Ann. Surg. 1984; 199: 461–466.
  13. Tisell L.E., Dilley W.G., Wells S.A. Jr. Progression of post operative residual medullary thyroid carcinoma as monitored by plasma calcitonin levels. Surgery. 1996; 119: 34–39.
  14. Giraudet A.L., Al Ghulzan A., Aupérin A. et al. Progression of medullary thyroid carcinoma: assessment with calcitonin and carcinoembryonic antigen doubling times. Eur. J. Endocrinol. 2008; 158: 239–246.
  15. Barbet J., Campion L., KraeberBodere F., Chatal J.F. Prog nostic impact of serum calcitonin and carcinoembryonic anti gen doublingtimes in patients with medullary thyroid carci noma. J. Clin. Endocrinol. Metab. 2005; 90: 6077–6084.
  16. Oudoux A., Salaun P.Y., Bournaud C. et al. Sensitivity and prognostic value of positron emission tomography with F18 fluorodeoxyglucose and sensitivity of immunoscintigraphy in patients with medullary thyroid carcinoma treated with anti carcinoembryonic antigentargeted radioimmunotherapy. J. Clin. Endocrinol. Metab. 2007; 92: 4590–4597.
  17. Ong S.C., Schoder H., Patel S.G. et al. Diagnostic accuracy of 18FFDG PET in restaging patients with medullary thyroid carcinoma and elevated calcitonin levels. J. Nucl. Med. 2007; 48: 501–507.
  18. Gourgiotis L., Sarlis N.J., Reynolds J.C. et al. Localization of medullary thyroid carcinoma metastasis in a multiple endocrine neoplasia type 2A patient by 6[18F]fluo rodopamine positron emission tomography. J. Clin. Endocrinol. Metab. 2003; 88: 637–641.
  19. Koopmans K.P., de Groot J.W., Plukker J.T. et al. 18Fdihy droxyphenylalanine PET in patients with biochemical evi dence of medullary thyroid cancer: relation to tumor differen tiation. J. Nucl. Med. 2008; 49: 524–531.
  20. Eisenhauer E.A., Therasse P., Bogaerts J. et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur. J. Cancer. 2009; 45: 228–247.
  21. Therasse P., Arbuck S.G., Eisenhauer E.A. et al. New guide lines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J. Natl. Cancer Inst. 2000; 92: 205–216.
  22. McWilliams R.R., Giannini C., Hay I.D. et al. Management of brain metastases from thyroid carcinoma: a study of 16 patho logically confirmed cases over 25 years. Cancer. 2003; 98: 356–362.
  23. Chiu A.C., Delpassand E.S., Sherman S.I. Prognosis and treatment of brain metastases in thyroid carcinoma. J. Clin. Endocrinol. Metab. 1997; 82: 3637–3642.
  24. Salvati M., Frati A., Rocchi G., Masciangelo R. et al. Single brain metastasis from thyroid cancer: report of twelve cases and review of the literature. J. Neurooncol. 2001; 51: 33–40.
  25. Kim I.Y., Kondziolka D., Niranjan A. et al. Gamma knife radio surgery for metastatic brain tumors from thyroid cancer. J. Neurooncol. 2009; 93: 355–359.
  26. Mont’Alverne F., Vallee J.N., Cormier E. et al. Percutaneous vertebroplasty for metastatic involvement of the axis. Am. J. Neuroradiol. 2005; 26: 1641–1645.
  27. Goetz M.P., Callstrom M.R., Charboneau J.W. et al. Percuta neous imageguided radiofrequency ablation of painful metastases involving bone: a multicenter study. J. Clin. Oncol. 2004; 22: 300–306.
  28. Simon C.J., Dupuy D.E. Percutaneous minimally invasive therapies in the treatment of bone tumors: thermal ablation. Semin. Musculoskelet. Radiol. 2006; 10: 137–144.
  29. Masala S., Manenti G., Roselli M. et al. Percutaneous com bined therapy for painful sternal metastases: a radiofrequen cy thermal ablation (RFTA) and cementoplasty protocol. Anticancer. Res. 2007; 27: 4259–4262.
  30. Toyota N., Naito A., Kakizawa H. et al. Radiofrequency ablation therapy combined with cementoplasty for painful bone metastases: initial experience. Cardiovasc. Intervent. Radiol. 2005; 28: 578–583.
  31. Chiras J., Adem C., Vallee J.N. et al. Selective intraarterial chemoembolization of pelvic and spine bone metastases. Eur. Radiol. 2004; 14: 1774–1780.
  32. Guzman R., DubachSchwizer S., Heini P. et al. Preoperative transarterial embolization of vertebral metastases. Eur. Spine. J. 2005; 14: 263–268.
  33. Baba Y., Hayashi S., Ueno K., Nakajo M. Bone cement used as an embolic agent for active bleeding in vertebroplasty of metastatic lesions. Acta Radiol. 2007; 48: 1024–1027.
  34. Bernier M.O., Leenhardt L., Hoang C. et al. Survival and ther apeutic modalities in patients with bone metastases of differentiated thyroid carcinomas. J. Clin. Endocrinol. Metab. 2001; 86: 1568–1573.
  35. Zettinig G., Fueger B.J., Passler C. et al. Longterm followup of patients with bone metastases from differentiated thyroid carcinoma – surgery or conventional therapy? Clin. Endocrinol. 2002; 56: 377–382.
  36. Brierley J.D., Tsang R.W. External beam radiation therapy for thyroid cancer. Endocrinol. Metab. Clin. North. Am. 2008; 37: 497–509.
  37. Vitale G., Fonderico F., Martignetti A. et al. Pamidronate improves the quality of life and induces clinical remission of bone metastases in patients with thyroid cancer. Br. J. Cancer. 2001; 84: 1586–1590.
  38. Tsutsui H., Kubota M., Yamada M. et al. Airway stenting for the treatment of laryngotracheal stenosis secondary to thy roid cancer. Respirology. 2008; 13: 632–638.
  39. Deandreis D., Leboulleux S., Dromain C. et al. Role of FDG PET/CT and chest CT in the followup of lung lesions treated with radiofrequency ablation. Radiology. 2011; 258: 270–276.
  40. Berber E., Flesher N., Siperstein A.E. Laparoscopic radiofre quency ablation of neuroendocrine liver metastases. Wld J. Surg. 2002; 26: 985–990.
  41. Mazzaglia P.J., Berber E., Milas M., Siperstein A.E. Laparo scopic radiofrequency ablation of neuroendocrine liver metastases: a 10year experience evaluating predictors of survival. Surgery. 2007; 142: 10–19.
  42. Wertenbroek M.W., Links T.P., Prins T.R. et al. Radio frequency ablation of hepatic metastases from thyroid carci noma. Thyroid. 2008; 18: 1105–1110.
  43. Lorenz K., Brauckhoff M., Behrmann C. et al. Selective arte rial chemoembolization for hepatic metastases from medullary thyroid carcinoma. Surgery. 2005; 138: 986–993, discussion 993.
  44. Fromigue J., De Baere T., Baudin E. et al. Chemoemboli zation for liver metastases from medullary thyroid carcinoma. J. Clin. Endocrinol. Metab. 2006; 91: 2496–2499.
  45. Shimaoka K., Schoenfeld D.A., DeWys W.D. et al. A rando mized trial of doxorubicin versus doxorubicin plus cisplatin in patients with advanced thyroid carcinoma. Cancer. 1985; 56: 2155–2160.
  46. Williams S.D., Birch R., Einhorn L.H. Phase II evaluation of doxorubicin plus cisplatin in advanced thyroid cancer: a Southeastern Cancer Study Group Trial. Cancer Treat. Rep. 1986; 70: 405–407.
  47. Orlandi F., Caraci P., Berruti A. et al. Chemotherapy with dacarbazine and 5fluorouracil in advanced medullary thyroid cancer. Ann. Oncol. 1994; 5: 763–765.
  48. Wu L.T., Averbuch S.D., Ball D.W. et al. Treatment of advanced medullary thyroid carcinoma with a combination of cyclophosphamide, vincristine, and dacarbazine. Cancer. 1994; 73: 432–436.
  49. Schlumberger M., Abdelmoumene N., Delisle M.J., Couette J.E. Treatment of advanced medullary thyroid cancer with an alternating combination of 5 FUstreptozocin and FUdacarbazine. The Groupe d’Etude des Tumeurs a Calcitonine (GETC). Br. J. Cancer. 1995; 71: 363–365.
  50. Bajetta E., Rimassa L., Carnaghi C. et al. 5Fluorouracil, dacarbazine, and epirubicin in the treatment of patients with neuroendocrine tumors. Cancer. 1998; 83: 372–378.
  51. Petursson S.R. Metastatic medullary thyroid carcinoma. Complete response to combination chemotherapy with dacarbazine and 5fluorouracil. Cancer. 1988; 62: 1899–1903.
  52. Nocera M., Baudin E., Pellegriti G. et al. Treatment of advan ced medullary thyroid cancer with an alternating combination of doxorubicinstreptozocin and 5 FUdacarbazine. Groupe d’Etude des Tumeurs а Calcitonine (GETC). Br. J. Cancer. 2000; 83: 715–718.
  53. Papewalis C., Wuttke M., Seissler J. et al. Dendritic cell vac cination with xenogenic polypeptide hormone induces tumor rejection in neuroendocrine cancer. Clin. Cancer Res. 2008; 14: 4298–4305.
  54. Iten F., Müller B., Schindler C. et al. Response to [90 Yttrium DOTA]TOC treatment is associated with longterm survival benefit in metastasized medullary thyroid cancer: a phase II clinical trial. Clin. Cancer Res. 2007; 13: 6696–6702.
  55. KraeberBodere F., Goldenberg D.M., Chatal J.F., Barbet J. Pretargeted radioimmunotherapy in the treatment of meta static medullary thyroid cancer. Curr. Oncol. 2009; 16: 3–8.
  56. Pasieka J.L., McEwan A.J., Rorstad O. The palliative role of 131 IMIBG and 111 Inoctreotide therapy in patients with metastatic progressive neuroendocrine neoplasms. Surgery. 2004; 136: 1218–1226.
  57. Wells S.A. Jr., Santoro M. Targeting the RET pathway in thy roid cancer. Clin. Cancer Res. 2009; 15: 7119–7123.
  58. Capp C., Wajner S.M., Siqueira D.R. et al. Increased expres sion of vascular endothelial growth factor and its receptors, VEGFR1 and VEGFR2, in medullary thyroid carcinoma. Thyroid. 2010; 20: 863–871.
  59. Cohen E.E.W., Rosen L.S., Vokes E.E. et al. Axitinib is an active treatment for all histologic subtypes of advanced thy roid cancer: Results from a phase II study. J. Clin. Oncol. 2008; 26: 4708–4713.
  60. Nemunaitis J.J. et al. Phase I doseescalation study of E7080, a multikinase inhibitor, in patients with advanced solid tumors. J. Clin. Oncol. (Meeting Abstracts). 2008; 26: 145-83.
  61. Schlumberger M., Elisei R., Bastholt L. et al. Phase II study of safety and efficacy of motesanib (AMG 706) in patients with progressive or symptomatic, advanced or metastatic medullary thyroid cancer. J. Clin. Oncol. 2009; 27: 3794–3801.
  62. Bible K.C. et al. Phase 2 trial of pazopanib in rapidly progres sive, metastatic, medullary thyroid cancer. Thyroid (Meeting Abstracts). 2009; 19: S1-10.
  63. Lam E.T., Ringel M.D., Kloos R.T. et al. Phase II clinical trial of sorafenib in metastatic medullary thyroid cancer. J. Clin. Oncol. 2010; 28: 2323–23-30.
  64. De Souza J.A. et al. Phase II trial of sunitinib in medullary thy roid cancer (MTC). J. Clin. Oncol. (Meeting Abstracts). 2010; 28: 550-4.
  65. Carr L.L., Mankoff D.A., Goulart B.H. et al. Phase II study of daily sunitinib in FDGPETpositive, iodinerefractory diffe rentiated thyroid cancer and metastatic medullary carcinoma of the thyroid with functional imaging correlation. Clin. Cancer Res. 2010; 16: 5260–5268.
  66. Kurzrock R., Sherman S.I., Ball D.W. et al. Activity of XL184 (cabozantinib), an oral tyrosine kinase inhibitor, in patients with medullary thyroid cancer. J. Clin. Oncol. 2011; 29: 2660–2666.
  67. Papotti M., Olivero M., Volante M. et al. Expression of hepatocyte growth factor (HGF) and its receptor (MET) in medullary carcinoma of the thyroid. Endocr. Pathol. 2000; 11: 19–30.
  68. Wells S., Gosnell J., Gagel R. et al. Vandetanib for the treat ment of patients with locally advanced or metastatic hereditary medullary thyroid cancer. J. Clin. Oncol. 2010; 28: 767–772.
  69. Robinson B.G., PazAres L., Krebs A. et al. Vandetanib (100 mg) in patients with locally advanced or metastatic hereditary medullary thyroid cancer. J. Clin. Endocrinol. Metab. 2010; 95: 2664–2671.
  70. Wells S.A., Robinson B.G., Gagel R.F. et al. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, doubleblind phase III trial (ZETA). J. Clin. Oncol. 2012; 30: 134–141.
  71. Hong D.S., Cabanillas M.E., Wheler J. et al. Inhibition of the Ras/Raf/MEK/ERK and RET kinase pathways with the combination of the multikinase inhibitor sorafenib and the far nesyltransferase inhibitor tipifarnib in medullary and differen tiated thyroid malignancies. J. Clin. Endocrinol. Metab. 2011; 96: 997–100-5.
  72. Hoff P.M. et al. Phase I/II trial of capecitabine (C), dacar bazine (D) and imatinib (I) (CDI) for patients (pts) metastatic medullary thyroid carcinomas (MTC). J. Clin. Oncol. (Meeting Abstracts). 2006; 24: 130-48.
  73. Jensen R.T. Overview of chronic diarrhea caused by func tional neuroendocrine neoplasms. Semin. Gastrointest. Dis. 1999; 10: 156–172.
  74. Rambaud J.C., Jian R., Flourie B. et al. Pathophysiological study of diarrhoea in a patient with medullary thyroid carcino ma. Evidence against a secretory mechanism and for the role of shortened colonic transit time. Gut. 1988; 29: 537–543.
  75. Barbosa S.L., Rodien P., Leboulleux S. et al. Ectopic adreno corticotropic hormone syndrome in medullary carcinoma of the thyroid: a retrospective analysis and review of the litera ture. Thyroid. 2005; 15: 618–623.
  76. Mahler C., Verhelst J., de Longueville M., Harris A. Longterm treatment of metastatic medullary thyroid carcinoma with the somatostatin analogue octreotide. Clin. Endocrinol. 1990; 33: 261–269.
  77. Lupoli G., Cascone E., Arlotta F. et al. Treatment of advanced medullary thyroid carcinoma with a combination of recombi nant interferon alpha2b and octreotide. Cancer. 1996; 78: 1114–1118.
  78. Kamenicky P., Droumaguet C., Salenave S. et al. Mitotane, metyrapone, and ketoconazole combination therapy as an alternative to rescue adrenalectomy for severe ACTHdepen dent Cushing’s syndrome. J. Clin. Endocrinol. Metab. 2011; 96: 2796–2804.


Abstract - 884

PDF (Russian) - 620

Copyright (c) 2013 ., ., .

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.