External Beam Radiation With or Without Concurrent Chemotherapy in Non-anaplastic Thyroid Cancer With Unresectable or Gross Residual Disease
Thomas H. BeckhamEric J. ShermanA. ShahaMona M. SabraC. SabolT. BrinkmanD. SpielsingerRM TuttleJames A. FaginRlc WongN. LeePaul B. Romesser
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Anaplastic thyroid cancer
Regimen
Medullary Thyroid Cancer
Niclosamide
Anaplastic thyroid cancer
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The incidence of thyroid cancer is growing the fastest among all cancers in the United States, especially in women.The number of patients with thyroid neoplasm is part of an even larger number of patients who often need to undergo an operation to exclude a cancer diagnosis.While differentiated thyroid cancer (papillary thyroid cancer and follicular thyroid cancer) accounts for most cases of thyroid cancer and has a relatively good prognosis, effective treatments for patients with de-differentiated and anaplastic thyroid cancer are still gravely needed.Despite progress in the identification of genetic changes in thyroid cancer, the impact of aberrant epigenetic alterations on thyroid cancer remains to be fully elucidated.Understanding of the roles of epigenetic changes in thyroid cancer could open new opportunities for the identification of innovative molecular targets for novel treatment modalities, especially for anaplastic thyroid cancer for which treatment is very limited.This article briefly reviews the studies that exemplify the potential for and promise of using epigenetic regulators in the treatment of thyroid cancer.
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Follicular thyroid cancer
Thyroid neoplasm
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2038 Objectives: 1. To highlight the importance of Nuclear Medicine imaging in the evaluation of radioactive iodine (RAI) refractory Thyroid Cancer. 2. To present the contribution of FDG PET/CT on poorly differentiated thyroid cancer (PDTC) or anaplastic thyroid cancer (ATC) patients’ management. 3. To discuss the future role of theranostics using PSMA ligands.
Abstract Body: Thyroid cancer is the most common endocrine malignancy, with the vast majority of such patients respond favorably to surgery and risk-adapted postoperative treatment with TSH suppression and RAI. The best response is seen in well-differentiated thyroid cancers (WDTC), papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC). However, a subset of patients presents with aggressive and less differentiated thyroid cancer refractory to RAI therapy. While DTC can become resistant to RAI therapy, resistance is most commonly seen in dedifferentiated subtypes, such as PDTC and ATC. Both PDTC and ATC may arise from WDTC. Surgery is often considered the only chance for survival, while the benefit of subsequent multimodal therapy is unclear. Among several clinical factors that predict RAI refractory at early evaluation, Nuclear Imaging plays a crucial role with F-18 FDG PET positivity - no Iodine uptake. Additionally, F-18 FDG PET scan is suggested having impact on PDTC or ATC patients’ management, indicating extended survival, if negative. The effect of targeted treatment protocols is also assessed in several studies by F-18 FDG PET scans. Furthermore, PSMA expression in aggressive forms of thyroid cancer gives opportunities for imaging and therapy. This educational exhibit aims to provide a brief but comprehensive review of recent developments to the clinical management of patients with anaplastic and poorly differentiated Thyroid Cancer.
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Refractory (planetary science)
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The aim of study is an evaluation of the diagnostic methods and results of surgical treatment 202 patients suffered from thyroid cancer. Those patients were operated on in II Department of Surgery Medical University of Gdańsk in the years 1950-1993. There were 146 female and 56 males. Most frequently histological finding was papillar cancer--71 cases, follicular cancer in 57 cases, medullar cancer in 31 cases and anaplastic cancer in 43 cases. FNB diagnosis of the cancer was established 89% of the patients before operation, during operation in 96% cases. In the majority of the patients with papillar cancer total thyroidectomy were carried out but the medullar and anaplastic cancer this treatment was possible only in small numbers of cases. In majority of those patients adjuvant treatment was performed. 128 patients with well-differentiated thyroid cancer was treated 131. Radiotherapy have been applied in all patients with medullar and anaplastic cancer. In cases of well-differentiated thyroid cancer the serum thyroglobulin level was also determined.
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Sorafenib and lenvatinib can be effective for advanced differentiated thyroid cancer, and vandetanib and cabozantinib can be effective options for advanced medullary thyroid cancer. When first-line tyrosine kinase inhibitors fail for patients, evidence supports salvage therapy for differentiated thyroid cancer but is less compelling for medullary thyroid cancer.
Lenvatinib
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The 2013 discovery of Telomerase reverse transcriptase ( TERT ) promoter mutations chr5, 1,295,228 C>T (C228T) and 1,295,250 C>T (C250T) in thyroid cancer represents an important event in the thyroid cancer field and much progress has occurred since then. This article provides a comprehensive review of this exciting new thyroid cancer field. The oncogenic role of TERT promoter mutations involves their creation of consensus binding sites for E-twenty-six transcriptional factors. TERT C228T is far more common than TERT C250T and their collective prevalence is, on average, 0, 11.3, 17.1, 43.2 and 40.1% in benign thyroid tumors, papillary thyroid cancer (PTC), follicular thyroid cancer, poorly differentiated thyroid cancer and anaplastic thyroid cancer, respectively, displaying an association with aggressive types of thyroid cancer. TERT promoter mutations are associated with aggressive thyroid tumor characteristics, tumor recurrence and patient mortality as well as BRAF V600E mutation. Coexisting BRAF V600E and TERT promoter mutations have a robust synergistic impact on the aggressiveness of PTC, including a sharply increased tumor recurrence and patient mortality, while either mutation alone has a modest impact. Thus, TERT with promoter mutations represents a prominent new oncogene in thyroid cancer and the mutations are promising new diagnostic and prognostic genetic markers for thyroid cancer, which, in combination with BRAF V600E mutation or other genetic markers (e.g. RAS mutations), are proving to be clinically useful for the management of thyroid cancer. Future studies will specifically define such clinical utilities, elucidate the biological mechanisms and explore the potential as therapeutic targets of TERT promoter mutations in thyroid cancer.
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Protein kinase inhibitors (PKIs) have emerged as highly promising therapies in progressive metastatic radioiodine-refractory differentiated thyroid cancer and in medullary thyroid cancer; two were recently approved in the USA for use in medullary thyroid cancer (vandetanib, cabozantinib), and another for use in progressive metastatic radioiodine-refractory differentiated thyroid cancer (sorafenib). Although more than 90% of thyroid cancer patients fare well in response to conventional treatment, PKI therapy has the potential to provide benefit. Nonetheless, PKIs produce numerous side effects, may worsen quality of life, may hasten mortality (by 1–2%), require discerning clinical acumen, are not yet proven to improve thyroid cancer survival and are very costly. This raises questions about who should prescribe PKIs, and about whether their use in thyroid cancer is truly beneficent and ethically justified. Restraint should be exercised in their use in thyroid cancer, with potential risks and benefits carefully weighed and solutions devised to help ameliorate many of the problems associated with their use.
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Medullary Thyroid Cancer
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The treatment of advanced thyroid cancer is currently entering a new era due to the introduction of targeted therapy into modern cancer treatment. The growing insight into the molecular biology of thyroid cancer and on the development of numerous mainly multitargeted agents provide the basis for new treatment strategies. In particular, activation of mitogenic and angiogenic signalling pathways are suitable targets as preclinical and clinical data suggest. Several Phase II and a few Phase III studies were launched in thyroid cancer which included medullary thyroid cancer (MTC) and anaplastic thyroid cancer (ATC) but only a few focused specifically on theses subtypes. A number of smaller Phase II trials reported promising response rates and progression-free survival. Results from a randomised Phase III trial in MTC with vandetanib, a combined vascular endothelial growth factor receptor 2 + 3 (VEGF-R2+3) and RET multi tyrosine kinase inhibitor demonstrated significant clinical activity and resulted in the first approval of a kinase inhibitor for the treatment of MTC in 2011. Unlike in MTC, in ATC the prognosis is dismal due to the aggressive nature of the disease. Some mainly vascular targeting agents alone or in combination with chemotherapy have shown interesting activity in this disease and have raised new hope. Particularly the combination of fosbretabulin with a chemotherapy backbone of paclitaxel and carboplatin tripled the one-year survival rate in a recent Phase II trial which included 80 patients with ATC. In this review, we provide a brief overview of the general treatment concept of MTC and ATC and summarise the compiled evidence published on targeted agents in these rare thyroid cancer subtypes.
Vandetanib
Medullary Thyroid Cancer
Anaplastic thyroid cancer
Targeted Therapy
Carboplatin
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Anaplastic thyroid cancer
Medullary Thyroid Cancer
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The treatment of thyroid cancer is evolving. The molecular mechanisms of carcinogenesis for many thyroid cancers have been investigated, and have yielded targets for potential therapies. These targets include VEGFR in the treatment of all thyroid cancers, BRAF in the treatment of papillary thyroid cancer, and RET in the treatment of medullary thyroid cancer (MTC). Many promising drugs that target one or more of these proteins are currently being evaluated, including sorafenib and sunitinib, both of which are still under development for the treatment of thyroid cancer but which have been approved for use in other malignancies. In addition, compounds such as vandetanib (AstraZeneca plc) and XL-184 (Bristol-Myers Squibb Co/Exelixis Inc) have demonstrated activity in early-phase clinical trials of MTC and are being tested further in randomized trials.
Vandetanib
Medullary Thyroid Cancer
Investigational Drugs
Follicular thyroid cancer
Targeted Therapy
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