New advances in the diagnosis, medical management and follow-up of medullary thyroid cancer

Abstract

Abstract Medullary thyroid cancer (MTC), which behaves more aggressively than the other well-differentiated thyroid cancers of follicular cell origin, accounts for 10% of all thyroid cancer-related deaths. Most MTCs are sporadic however approximately 25% is hereditary as part of the multiple endocrine neoplasia syndrome type 2 (MEN 2a and 2b). Both sporadic and inherited forms of MTC have a propensity for lymphatic and distant metastasis. The primary treatment of MTC is total thyroidectomy and removal of all neoplastic tissues present in the neck. After surgical treatment, measurements of serum calcitonin and carcinoembryonic antigen are of paramount importance in the postoperative follow-up since these markers reflect the presence of persistent or recurrent disease. Systemic chemotherapy with dacarbazine, 5-fluorouracil and doxorubicin, either alone or in combination, has shown very limited efficacy, producing only partial responses in the range of 10-20% and of short duration. Although current treatment options for patients with metastatic and refractory MTC are limited, recent advances in molecular oncology have fostered the invention of novel small molecules which target specific pathways which are thought to be essential in the MTC carcinogenesis. Several kinase inhibitors are currently under evaluation and preliminary results are promising. Keywords: Medullary thyroid cancer, thyrosine kinase inhibitors Ozet Meduller Tiroid Kanseri (MTC) folikul hucrelerinden kaynaklanan iyi diferansiye tiroid kanserlerinden daha agresif seyreder ve tiroid hastaliklarina bagli olusan olumlerin yaklasik %10’unu olusturur. MTC’rinin cogu sporadik olarak ortaya cikar fakat %25’i MEN Tip 2’nin bir parcasi olarak herediter olabilir. MTC’nin her 2 formunda da lenf nodu metastazi ve uzak metastaz gorulebilir. Hem sporadik hem de herediter formun primer tedavisi total tiroidektomi ve boyundaki tumor dokusunun tamaminin cikarilmasidir. Total tiroidektomi sonrasi serum CT (kalsitonin) ve CEA olcumu MTC hastalarin operasyon sonrasi takibinde onemlidir cunku bu belirteclerdeki artis persistan veya rekurren hastalik oldugunu dusundurur. Dakarbazin, 5-florourasil ve doksorubisinle (tek veya kombinasyon seklinde) sistemik kemoterapinin etkisi oldukca sinirlidir, kismi cevap %10-20 arasindadir ve kisa surelidir. Metastatik veya rekurren MTC hastalarinda gunumuzde tedavi secenekleri sinirli olmasina ragmen molekuler onkolojideki son ilerlemeler MTC tumor olusumunda onemli oldugu dusunulen spesifik yolaklara yonelik kucuk molekullerin gelisimini hizlandirmistir. Bazi kinaz inhibitorleri MTC’lerinde denenmektedir ve on sonuclar umit vericidir. Anahtar sozcukler: Meduller tiroid kanseri, tirozin kinaz inhibitorleri