Is there a role for sandostatin treatment in patients with progressive thyroid cancer and iodine-negative but somatostatin-receptor-positive metastases?

INTRODUCTION: The aim of our study was to determine whether treatment with a long-acting somatostatin-receptor analogue is effective in patients with (131)I-negative but somatostatin-receptor-positive metastases from dedifferentiated and anaplastic thyroid cancer. MATERIALS AND METHODS: Twelve patients were screened for the study. All of them showed progressive disease confirmed by radiologic evaluation, increasing serum thyroglobulin (Tg), and negative diagnostic or posttherapeutic (131)I whole-body scans (WBS). Eight of 12 patients (4 males and 4 females; age range, 57-89 years; 1 papillary thyroid cancer; 4 poorly differentiated follicular thyroid cancer; 1 follicular and anaplastic thyroid cancer; 2 anaplastic thyroid cancer) showed positive somatosatin-receptor expression in Tc-99m depreotide WBS/SPECT (Tc-99m Dep.WBS). Initially, in all patients fluorine-18 2-fluoro-2- D-glucose-positron emission tomography-computed tomography ((18)F-FDG-PET-CT), Tc-99m Dep.WBS, and Tg measurements were performed. In the case of positive receptor scintigraphy, patients were treated with 20mg Sandostatin LAR (Novartis Pharmaceuticals, Basel, Switzerland) once per month intramuscularly over a period of 6 months followed by repeated (18)F-FDG-PET-CT, Tc-99m Dep.WBS, and Tg measurement to determine metabolic activity and tumor size. In case of tumor progression, the dose was increased to 30mg of Sandostatin LAR once per month. RESULTS: Only 3 patients were able to undergo long-term treatment. Two patients were treated with octreotide long-acting release (LAR) for 1 year and 1 patient for 1(1/2) years. All patients showed progressive disease during the treatment: an increase of serum Tg on one hand and an increase in the number of lesions and extent in tumor size visible on FDG-PET-CT and Tc-99m Dep.WBS on the other. During the treatment there was no change in receptor expression, nevertheless, clear tumor progression under therapy with a somatostatin analogue was visible in FDG-PET-CT and in Tc-99m Dep.WBS. CONCLUSION: Our data demonstrate that all of our patients treated with a somatostatin analogue showed clinical progression and that our attempt to achieve a stabilization of the disease failed.

18F-FDG-PET in the follow-up of thyroid cancer.

Differentiated thyroid cancer is a rare tumour with an incidence of 4 - 9/100,000/year. For preoperative assessment of thyroid nodules, ultrasonography (US) and US-guided fine needle aspiration biopsy are the methods of choice to detect thyroid cancer. The value of preoperative fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG-PET) in differentiating malignant from benign nodules, especially in cases of follicular proliferation, has not yet been evaluated. After thyroidectomy and radioiodine remnant ablation, several methods are used to follow patients with differentiated thyroid cancer, including serum thyroglobulin, ultrasonography of the neck, iodine-131 (131I) whole body scintigraphy (WBS) and scintigraphy with nonspecific tracers such as technetium-99 m ((99m)Tc) Tetrofosmin or Sestamibi. Whereas the specificity of 131I-WBS is high, sensitivity is low, especially if one takes into account that only two-thirds of recurrences or metastases store iodine. With the introduction of 18F-FDG in oncology, it is also used for the detection of local recurrences and metastases of differentiated thyroid cancer. Elevated thyroglobulin but negative 131I-WBS belongs to the 1a indications for 18F-FDG-PET in oncology according to the German Consensus Conference 2000. The sensitivity for detecting 131I-negative metastases with 18F-FDG-PET can be increased by elevated thyroid-stimulating hormone (TSH) after withdrawal of thyroid hormone therapy or after intramuscular injection of recombinant TSH. Most of the 131I-negative metastases demonstrate 18F-FDG uptake, which represents rapid tumour growth and poor differentiation, whereas most of the 131I-positive metastases are 18F-FDG negative. The combination of 131I-WBS and 18F-FDG-PET leads to an increase in the detection rate to more than 90 - 95 % in cases of elevated thyroglobulin, because well- and less-differentiated cancer cells may be present in one patient. In rare cases, a recurrent tumour or metastasis may accumulate 131I as well as 18F-FDG. In these patients, it may be possible that well- and less-differentiated cells are present in one metastasis. The early use of 18F-FDG-PET in patients with elevated thyroglobulin, especially in the case of negative 131I-WBS, changes the therapeutic strategy in up to half of the patients (surgery, external radiation).