The Role of Radiation Therapy in the Treatment of Medullary Thyroid Cancer

2010 ◽  
Vol 8 (5) ◽  
pp. 532-541 ◽  
Author(s):  
Stephanie A. Terezakis ◽  
Nancy Y. Lee
Keyword(s):  
Thyroid Cancer ◽  
Medullary Thyroid Cancer ◽  
Radiation Treatment ◽  
Locally Advanced ◽  
External Beam Radiation ◽  
Beam Radiation ◽  
Medullary Thyroid ◽  
Adequate Dose ◽  
Radiation Technique

Medullary thyroid cancer (MTC) is a neuroendocrine tumor derived from parafollicular or C cells of the thyroid gland. Surgical resection is the mainstay of treatment for MTC. External-beam radiation treatment (EBRT) has traditionally played a limited role in the management of MTC. Despite aggressive surgery, patients at high risk for local recurrence may benefit from adjuvant EBRT. With improvements in radiation technique, adequate dose can be effectively delivered to the region at risk while minimizing dose to surrounding critical structures. Although the role of EBRT in the management of these tumors has thus far been poorly defined, EBRT should be considered as a treatment option for patients with locally advanced MTC to optimize locoregional control.

YAP confers resistance to vandetanib in medullary thyroid cancer

2020 ◽  
Vol 98 (3) ◽  
pp. 443-448
Author(s):  
Huan Wang ◽  
Jian Tang ◽  
Zhiwei Su
Keyword(s):  
Thyroid Cancer ◽  
Medullary Thyroid Cancer ◽  
Critical Role ◽  
Acquired Resistance ◽  
Resistant Cell ◽  
Resistant Cell Line ◽  
Antitumor Effects ◽  
Medullary Thyroid ◽  
Tt Cells

Medullary thyroid cancer (MTC) is the third most common thyroid cancer. RET (Rearranged in Transformation) gene mutations are considered as one of the major drivers of MTC. Vandetanib suppresses RET activity, and has shown promise in clinical trials. Unfortunately, acquired resistance to vandetanib has been observed in MTC, although the mechanism was largely unknown. We investigated the critical role of YAP (Yes-Associated Protein) on vandetanib resistance in MTC. For this, TT cells (medullary thyroid cancer cells) were treated with vandetanib for 3 months to generate a vandetanib-resistant cell line (TT-R). We investigated the role of YAP on vandetanib-resistance in TT-R cells by performing cell proliferation and colony formation assays, and examined the antitumor effects of YAP inhibitor and vandetanib in a mouse model of xenografted MTC. The TT-R cells displayed 6-fold higher IC50 to vandetanib than the TT cells. Overexpression of YAP resulted in resistance to vandetanib, whereas knockdown of YAP re-sensitized the TT-R cells to vandetanib. The YAP inhibitor synergized with vandetanib on tumor inhibition. Our results suggest that YAP plays an important role in acquired resistance to vandetanib in MTC, providing basis for combating MTC with YAP inhibitor and vandetanib.

A phase II study of axitinib (AG-013736 [AG]) in patients (pts) with advanced thyroid cancers

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6008-6008 ◽  
Author(s):  
E. E. Cohen ◽  
E. E. Vokes ◽  
L. S. Rosen ◽  
M. S. Kies ◽  
A. A. Forastiere ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Thyroid Tumor ◽  
External Beam Radiation ◽  
Vegf Receptors ◽  
Beam Radiation ◽  
Thyroid Cancers ◽  
Advanced Thyroid Cancer ◽  
Multi Center Study

6008 Background: Elevated VEGF-A and VEGF-C have been reported in thyroid tumor tissue compared with normal thyroid. AG is a potent, small molecule inhibitor of VEGF receptors 1, 2 and 3. The efficacy and safety of AG therapy in pts with advanced thyroid cancers was examined in this single-arm, multi-center study. Methods: 60 pts with metastatic or unresectable locally-advanced thyroid cancer refractory to, or not suitable candidates for, 131iodine (131I) treatment, with measurable disease received AG at a starting dose of 5 mg orally BID. The primary endpoint was response rate (RR) by RECIST criteria. A Simon 2-stage minimax design was used (a=0.1; β=0.1; null RR=5%; alternative RR=20%). Samples were collected pretreatment and q8wks to explore relationships between clinical response and plasma soluble proteins. Results: Median age was 59 yrs (26–84), 35 (58%) were male. Histological subtypes included papillary: 29 pts (48%); follicular: 15 pts (25%)-11 (18%) with Hurthle cell variant; medullary: 12 pts (20%); anaplastic: 2 pts (3%), and other/unknown: 2 pts (3%). 53 pts (88%) had prior surgery, 42 (70%) had prior 131I treatment, 27 (45%) had prior external beam radiation, and 9 (15%) had prior chemotherapy. Partial response (PR) by investigator report was achieved in 13 pts (22% CI: 12.1, 34.2), with 31- 68% maximum tumor regression and duration of response (DOR) of 1–16 months. 30 pts (50%) have stable disease with a duration range of 4–13 months and 13–67% maximum tumor regression in 28 pts. Response assessments are ongoing. The treatment duration range is 6–670 days with 38 pts currently on study. Median PFS has not been reached with a median follow up of 273 days. The most common treatment-related adverse events were fatigue (37%), proteinuria (27%), stomatitis/mucositis (25%), diarrhea (22%), hypertension (20%) and nausea (18%). AG therapy consistently decreased soluble VEGFR2 and VEGFR3, and increased VEGF in the blood, demonstrating pharmacodynamic activity against targeted VEGF receptors. Conclusions: AG has substantial anti-tumor activity in advanced thyroid cancer with demonstrated pharmacodynamic activity. A global pivotal trial testing AG in doxorubicin refractory thyroid cancer is ongoing. [Table: see text]

scholarly journals Previous External Beam Radiation Treatment Exposure Does Not Confer Worse Outcome for Patients with Differentiated Thyroid Cancer

Thyroid ◽  
2017 ◽  
Vol 27 (3) ◽  
pp. 412-417 ◽  
Author(s):  
Manish A. Shaha ◽  
Laura Y. Wang ◽  
Jocelyn C. Migliacci ◽  
Frank L. Palmer ◽  
Iain J. Nixon ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Differentiated Thyroid Cancer ◽  
Radiation Treatment ◽  
External Beam Radiation ◽  
External Beam ◽  
Beam Radiation

scholarly journals Vandetanib (ZD6474) in the Treatment of Medullary Thyroid Cancer

2011 ◽  
Vol 5 ◽  
pp. CMO.S6197 ◽  
Author(s):  
Hari Deshpande ◽  
Sanziana Roman ◽  
Jaykumar Thumar ◽  
Julie Ann Sosa
Keyword(s):  
Thyroid Cancer ◽  
Growth Factor ◽  
Phase Ii ◽  
Medullary Thyroid Cancer ◽  
Kinase Inhibitor ◽  
Locally Advanced ◽  
Growth Factor Receptor ◽  
Good Choice ◽  
Phase Ii Trials ◽  
Medullary Thyroid

Vandetanib (ZD6474) is an orally bioavailable small molecule tyrosine kinase inhibitor of multiple growth factor receptors, including RET (Rearrange during transfection), vascular endothelial growth factor receptor-2 (VEGFR-2) and epidermal growth factor receptor (EGFR). The activity against RET and VEGF made it a good choice in the treatment of medullary thyroid cancer (MTC). As there is considerable cross talk between growth factor pathways, dual inhibition with such agents has become an attractive strategy, in the treatment of many malignancies with encouraging Phase II clinical trial data to date. Vandetanib was tested in two Phase II trials in the treatment of patients with medullary thyroid cancer at doses of 100 mg and 300 mg daily respectively. The encouraging results of these 2 trials led to a randomized phase II trial comparing this medication to placebo using a crossover design. More than 300 patients were included in this study, which ultimately showed a significant improvement in progression-free survival in patients taking vandetanib. Based on these results, the Oncology Drug Advisory Committee (ODAC) of the Food and Drug Administration (FDA) recommended that vandetanib be approved for the treatment of patients with unresectable locally advanced or metastatic medullary thyroid cancer.

Sign in / Sign up

Export Citation Format

Share Document