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Combination therapy of medullary thyroid cancer using radiation and vandetanib

Konferensbidrag (offentliggjort, men ej förlagsutgivet)
Författare Viktor Sandblom
Johan Spetz
Emman Shubbar
John Swanpalmer
Eva Forssell-Aronsson
Publicerad i 30th Annual Congress of the European Association of Nuclear Medicine, 2017
Publiceringsår 2017
Publicerad vid Institutionen för kliniska vetenskaper, sektionen för onkologi, radiofysik, radiologi och urologi, Avdelningen för radiofysik
Språk en
Länkar eanm17.eanm.org/
Ämneskategorier Strålningsbiologi, Radiofysik, Cancer och onkologi

Sammanfattning

INTRODUCTION Most patients diagnosed with medullary thyroid cancer (MTC) present with metastatic disease. MTC are rare neuroendocrine tumours that occur either sporadically or in a hereditary form. Surgical resection of the thyroid gland followed by external beam radiotherapy (EBRT) or the use of tyrosine kinase inhibitors are current clinical methods for management of MTC. Unfortunately, the 10-year survival for patients with metastatic disease is only about 40%. However, many MTC tumours overexpress somatostatin receptors as molecular targets. Therefore, one option for patients with MTC is systemic treatment with radiolabelled somatostatin analogues (e.g. 177Lu-octreotate) that bind with high affinity and specificity to somatostatin receptors on the tumour cells. In addition, the tyrosine kinase inhibitor vandetanib has recently been approved for single-agent treatment of MTC by the U.S. Food and Drug Administration (FDA). The aim of this study was to investigate the potential synergistic effect of combining irradiation and vandetanib for treatment of MTC. SUBJECTS & METHODS BALB/c nude mice were transplanted with patient-derived MTC cells (GOT2). When developed tumours reached a volume of about 500 mm3, the mice were treated with EBRT, vandetanib or a combination of both. The radiation dose and the amount of vandetanib were chosen to give moderate effect as single treatment to enable detection of any increased effect from the combination. Tumour volume was followed and compared with that in untreated mice. RESULTS We found that the largest treatment effect over time was seen for the animals receiving a combination of both EBRT and vandetanib. Given as single-agent treatment, EBRT and vandetanib resulted in a reduction in tumour size or in tumour growth arrest. For example, at two weeks after start of treatment, the tumour volume was reduced by 64%, 52%, and 73% compared with the untreated control group, for the animals treated with single EBRT, single vandetanib, and the combination, respectively. CONCLUSION The results indicate that an additive or even synergistic effect could be achieved when combining irradiation with vandetanib for treatment of patients with MTC. Further studies are needed to investigate the possibility of using 177Lu-octreotate for treatment of MTC, both as single-agent treatment or in combination with vandetanib.

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