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Increased therapeutic effect on medullary thyroid cancer using a combination of radiation and tyrosine kinase inhibitors

Journal article
Authors Viktor Sandblom
Johan Spetz
Emman Shubbar
Mikael Montelius
Ingun Ståhl
John Swanpalmer
Ola Nilsson
Eva Forssell-Aronsson
Published in PLoS ONE
Volume 15
Issue 5
Pages e0233720
ISSN 1932-6203
Publication year 2020
Published at Institute of Clinical Sciences, Department of Radiation Physics
Sahlgrenska Cancer Center
Institute of Biomedicine
Pages e0233720
Language en
Links https://doi.org/10.1371/journal.pon...
Subject categories Cancer and Oncology, Radiological physics, Radiation biology

Abstract

Since patients with medullary thyroid cancer (MTC) often have metastatic disease at the time of diagnosis, the development of efficient systemic treatment options for MTC is important. Vandetanib and cabozantinib are two tyrosine kinase inhibitors (TKIs) that were recently approved by FDA and EMA for systemic treatment of metastatic MTC. Additionally, since MTC is of a neuroendocrine tumour type, treatment with radiolabelled somatostatin analogues (e.g. 177Lu-octreotate) is a valid option for patients with MTC. The aim of this study was to investigate the potentially increased therapeutic effect of combining radiation therapy with these TKIs for treatment of MTC in a mouse model. Nude mice carrying patient-derived MTC tumours (GOT2) were treated with external beam radiotherapy (EBRT) and/or one of the two TKIs vandetanib or cabozantinib. The tumour volume was determined and compared with that of mock-treated controls. The treatment doses were chosen to give a moderate effect as monotherapy to be able to detect any increased therapeutic effect from the combination therapy. At the end of follow-up, tumours were processed for immunohistochemical (IHC) analyses. The animals in the combination therapy groups showed the largest reduction in tumour volume and the longest time to tumour progression. Two weeks after start of treatment, the tumour volume for these mice was reduced by about 70-75% compared with controls. Furthermore, also EBRT and TKI monotherapy resulted in a clear anti-tumour effect with a reduced tumour growth compared with controls. The results show that an increased therapeutic effect could be achieved when irradiation is combined with TKIs for treatment of MTC. Future studies should evaluate the potential of using 177Lu-octreotate therapy in combination with TKIs in patients.

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