Endocrine Abstracts (2008) 16 S27.3

Therapeutic options and dilemmas in medullary thyroid carcinoma

Barbara Jarzab

Department of Nuclear Medicine and Endocrine Oncology, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland.

Analysis of RET germline mutations, now a routine element of diagnostic algorithm in medullary thyroid carcinoma (MTC), influences follow up of MTC patients but at present has less impact on treatment modalities, which are the same in hereditary and sporadic disease. Microarray analyses confirm that molecular profile is rather similar in both MTC forms.

In hereditary MTC, RET mutation screening in families at risk allows to find asymptomatic mutation carriers, for whom prophylactic thyroidectomy is to be offered. Still, some questions need consideration, among them:

• Should routine RET diagnostics in patients diagnosed with apparently sporadic MTC, behind the known hotspots in exons 10,11 and 13–16, involve all other mutations detected until now?

• Do genotype-phenotype differences justify a delay in prophylactic thyroidectomies in some families?

• What are the legal consequences of RET germline mutation detection?

If diagnosis of MTC is done at later stage, surgery is often unsuccessful and treatment of disseminated disease becomes the main problem both in hereditary and in sporadic MTC. Neither radiotherapy nor classical chemotherapy constitute successful therapy options. Thus, the recent introduction of new targeted therapy modalities has raised much interest. Before all, the use of tyrosine kinase inhibitors (TKI) is being considered. Each TKI has its own spectrum of target kinases and their potency to inhibit angiogenesis is especially important. It is well known that VEGFR expression is increased in MTC and contributes to its aggressiveness, thus, inhibition of VEGFR kinases offers a strong anti-cancer effect. RET protein itself is also a receptor tyrosine kinase, targeted by some TKI. Numerous phase 2 or phase 3 trials have been initiated and for some of them, results were already published and will be reviewed. In general, it appears that at least some TKI are able to show a clinically meaningful tumor control in MTC.

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