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1.
Histone Deacetylase Inhibitors and Anaplastic Thyroid Carcinoma.
Spartalis, E, Athanasiadis, DI, Chrysikos, D, Spartalis, M, Boutzios, G, Schizas, D, Garmpis, N, Damaskos, C, Paschou, SA, Ioannidis, A, et al
Anticancer research. 2019;(3):1119-1127
Abstract
BACKGROUND/AIM: Anaplastic thyroid cancer (ATC) is one of the most aggressive human malignancies, remaining generally incurable. Histone deacetylase (HDAC) seems to play a role in regulating transcription of genes involved in ATC, making HDAC inhibitors (HDACI) promising anticancer drugs for ATC. The purpose of this review was to evaluate the role of HDACIs in ATC treatment and describe the latest trends of current research on this field. MATERIALS AND METHODS This literature review was performed using the MEDLINE database. The keywords/phrases were; thyroid cancer, anaplastic, HDAC, histone, deacetylase*, HDACI. RESULTS Compounds, such as SuberoylAnilide Hydroxamic Acid, valproic acid, sodium butyrate, butyrate, phenylbutyrate, trichostatin A, AB1-13, panobinostat or LBH589, belinostat, MS-275, depsipeptide, CUDC101, CUDC907, N-Hydroxy-7-(2-naphthylthio)-Hepanomide (HNHA), and PXD101 have shown promising antitumor effects against ATC. CONCLUSION HDACIs represent a promising therapy for ATC management, both as monotherapy and in combination with other anticancer drugs.
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2.
124I Positron Emission Tomography/Computed Tomography Versus Conventional Radioiodine Imaging in Differentiated Thyroid Cancer: A Review.
Wu, D, Ylli, D, Heimlich, SL, Burman, KD, Wartofsky, L, Van Nostrand, D
Thyroid : official journal of the American Thyroid Association. 2019;(11):1523-1535
Abstract
Background: Studies report a wide spectrum of 124I positron emission tomography (PET)/computed tomography (CT) sensitivity and specificity in the detection of differentiated thyroid cancer (DTC) lesions. This study reviews the lesion detection rate of pretherapy 124I PET/CT in different patient populations and further analyzes the factors necessary for a better detection on 124I PET/CT. Methods: A literature search was performed using multiple different databases (MEDLINE, EMBASE, Northern Lights, and handsearching) covering 1996 to April 2018. Two reviewers reviewed and extracted study data for 124I, 123I, and 131I scans in DTC. Results: This review includes 4 retrospective and 10 prospective studies in which 495 DTC patients underwent 124I and 131I imaging; no studies made comparisons with 123I. In the reports that compared 124I PET/CT with diagnostic 131I scans, there were a total of 72 patients in whom 120 lesions were detected on 124I imaging, whereas only 52 were detected on diagnostic 131I scans. In publications that compared 124I with post-therapy 131I scans in 266 patients, 410 lesions were detected with 124I PET, whereas 390 were detected on post-therapy 131I scans. Based on 124I PET/CT in six studies, TNM staging was revised in 15-21% of patients, and disease management was altered in 5-29% of patients. Conclusions:124I PET/CT is able to identify a greater number of foci compared with diagnostic 131I scans. 124I PET may have better detection compared with post-therapy 131I scans in patients who are 131I therapy naive, have less aggressive pathology, or do not have disseminated lung metastases. Additional metastatic lesion detection by 124I PET may have a significant clinical impact in the management of patients before 131I therapy in some patients.
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3.
Sunitinib in the Treatment of Thyroid Cancer.
Ferrari, SM, Centanni, M, Virili, C, Miccoli, M, Ferrari, P, Ruffilli, I, Ragusa, F, Antonelli, A, Fallahi, P
Current medicinal chemistry. 2019;(6):963-972
Abstract
BACKGROUND Sunitinib (SU11248) is an oral multi-target tyrosine kinase inhibitor (TKI) with low molecular weight, that inhibits platelet-derived growth factor receptors (PDGF-Rs) and vascular endothelial growth factor receptors (VEGFRs), c-KIT, fms-related tyrosine kinase 3 (FLT3) and RET. The concurrent inhibition of these pathways reduces tumor vascularization and causes cancer cell apoptosis, inducing a tumor shrinkage. Sunitinib is approved for the treatment of imatinib-resistant gastrointestinal stromal tumor (GIST), renal carcinoma, and pancreatic neuroendocrine tumors. METHODS We searched the literature on PubMed library. RESULTS In vitro studies showed that sunitinib targeted the cytosolic MEK/ERK and SAPK/JNK pathways in the RET/PTC1 cell inhibiting cell proliferation and causing stimulation of sodium/iodide symporter (NIS) gene expression in RET/PTC1 cells. Furthermore sunitinib is active in vitro and in vivo against anaplastic thyroid cancer (ATC) cells. Most of the clinical studies report that sunitinib is effective as first- and second-line TKI therapy in patients with advanced dedifferentiated thyroid cancer (DeTC), or medullary thyroid cancer (MTC). Sunitinib 37.5 mg/day is well tolerated, and effective. The most common adverse events include: reduction in blood cell counts (in particular leukocytes), hand-foot skin reaction, diarrhea, fatigue, nausea, hypertension, and musculoskeletal pain. CONCLUSION Even if sunitinib is promising in the therapy of differentiated thyroid carcinoma (DTC), until now no phase III studies have been published, and additional prospective researches are necessary in order to evaluate the real efficacy of sunitinib in aggressive thyroid cancer.
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4.
Management of treatment-related toxicities in advanced medullary thyroid cancer.
Tsang, VHM
Current opinion in oncology. 2019;(3):236-242
Abstract
PURPOSE OF REVIEW Tyrosine kinase inhibitors (TKI), predominantly vandetanib and cabozantinib, are increasingly used for management of advanced medullary thyroid cancer. This review aims to discuss the major and serious adverse events associated with TKI. RECENT FINDINGS The choice of TKI depends on the patient's existing comorbidities. Patients who have long QT interval should avoid vandetanib and those at risk of gastrointestinal perforation should avoid cabozantinib. Hypertension is common during the first 3 months. Treatments include ACE inhibitors, calcium channel blockers (avoiding verapamil and diltiazem, which are CYP3A4 inhibitors), and beta blockers. Diuretics should be second line because of derangement of electrolytes, which may exacerbate QT interval. As nitric oxide (NO) blockade and ET1 are implicated in the mechanism of hypertension, nitrates and endothelin receptor antagonists may be used. Thromboembolism may require anticoagulation or revascularization procedures. Prolonged QT interval should be treated by dose interruption and reduction, correction of electrolytes, and avoidance of medications, which prolong QTc interval. Diarrhoea is managed symptomatically and with electrolyte replacement, dermatological adverse events with avoidance of exacerbating factors and topical therapies. Thyroid function should be monitored. SUMMARY Toxicities are common with TKI use, and management involves symptomatic treatment, avoidance of triggers, dose interruption, and dose reduction.
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5.
Vitamin D deficiency as a risk factor for thyroid cancer: A meta-analysis of case-control studies.
Zhao, J, Wang, H, Zhang, Z, Zhou, X, Yao, J, Zhang, R, Liao, L, Dong, J
Nutrition (Burbank, Los Angeles County, Calif.). 2019;:5-11
Abstract
OBJECTIVE The association between vitamin D deficiency and thyroid cancer is controversial. Some studies have demonstrated that higher serum vitamin D levels might protect against thyroid cancer, whereas others have not, or have even indicated the opposite to be the case. The aim of this meta-analysis was to investigate the association between vitamin D deficicency and thyroid cancer and propose that vitamin D deficiency is a risk factor for thyroid cancer. METHODS This was a meta-analysis of 14 articles of the association between vitamin D deficiency and thyroid cancer. Databases including PubMed, Cochrane library, Sinomed, CNKI, Wanfang, and clinical trial register centers, were searched for case-control studies of vitamin D in thyroid cancer. RESULTS Fourteen studies were included in this meta-analysis. A fixed-effect model was used to merge the standardized mean difference value of serum 25-hydroxyvitamin D levels. The pooled effect showed that the levels of serum 25-hydroxyvitamin D were lower in patients with thyroid cancer preoperatively than in the controls (-0.22; 95% confidence interval [CI], -0.36 to -0.09; P = 0.001). There was no difference after thyroid cancer patients underwent thyroidectomy (-0.19; 95% CI, -0.47 to 0.10; P = 0.21). A fixed-effect model was used to pool the odds ratio of thyroid cancer and vitamin D deficiency. It showed that the pooled odds ratio from six studies was 1.30 (95% CI, 1.00-1.69; P = 0.05). Subgroup analysis of 25-hydroxyvitamin D levels between different pathologic characteristics in patients with thyroid cancer was summarized, but no statistical differences were determined. CONCLUSIONS Lower serum 25-hydroxyvitamin D levels were associated with increased risk for thyroid cancer. On the other hand, vitamin D deficiency may act as a risk factor for thyroid cancer.
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6.
Conventional Radioiodine Therapy for Differentiated Thyroid Cancer.
Ylli, D, Van Nostrand, D, Wartofsky, L
Endocrinology and metabolism clinics of North America. 2019;(1):181-197
Abstract
This article presents an overview of the use of radioactive iodine (131-I) in the treatment of patients with differentiated thyroid cancer. Topics reviewed include definitions; staging; the 2 principal methods for selection of 131-I dosage; the indications for ablation, adjuvant treatment, and treatment; the recommendations for the use of 131-I contained in the guidelines of the American Thyroid Association and the Society of Nuclear Medicine and Molecular Imaging; the dosage recommendations and selection of dosage approach for 131-I by these organizations; the use of recombinant human thyrotropin for radioiodine ablation, adjuvant therapy, or treatment; and the MedStar Washington Hospital Center approach.
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7.
Crucial parameters in thyroid carcinoma reporting - challenges, controversies and clinical implications.
Xu, B, Ghossein, RA
Histopathology. 2018;(1):32-39
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Abstract
In the modern era, a pathology report of thyroid carcinoma requires the inclusion of numerous prognostically relevant histopathological features, e.g. the presence and extent of vascular and capsular invasion, extrathyroidal extension, the surgical margin status and the characteristics of nodal metastasis. These pathological features are crucial components of the initial risk stratification to determine the need for completion thyroidectomy and/or postoperative radioactive iodine ablation therapy. The current review aims to summarise the diagnostic criteria, the controversies, the prognostic impacts and the challenges of these pathological characteristics, focusing specifically on the parameters that are incorporated into the American Joint Committee on Cancer (AJCC) staging system, the College of American Pathologists (CAP) reporting template, the American Thyroid Association (ATA) and the National Comprehensive Cancer Network (NCCN) guidelines.
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8.
RADIATION AND THYROID CANCER-AN OVERVIEW.
Thomas, G
Radiation protection dosimetry. 2018;(1):53-57
Abstract
It has long been known that the thyroid is a radiosensitive organ. It is the only organ in the body to both take up and bind iodine, and therefore exposure to radioiodine in fallout from nuclear power plants poses an increased danger to the thyroid. Studies following the Chernobyl accident have shown that children are most at risk from the development of thyroid cancer following exposure to radioactive iodine in fallout. This article reviews what we know so far about the type of thyroid cancer induced by radiation, its molecular biology and clinical outcome.
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Role of positron emission tomography in thyroid and neuroendocrine tumors.
Treglia, G, Kroiss, AS, Piccardo, A, Lococo, F, Santhanam, P, Imperiale, A
Minerva endocrinologica. 2018;(3):341-355
Abstract
Positron emission tomography (PET) is an established imaging method in oncology. PET/computed tomography (PET/CT) and PET/magnetic resonance imaging (PET/MRI) are hybrid techniques which combine morphological information obtained by CT and MRI with functional data provided by PET. Several PET radiotracers evaluating different metabolic pathways or receptor status can be used to assess endocrine tumors such as thyroid tumors or neuroendocrine neoplasms (NENs). This review is focused to describe the role of PET imaging using different radiotracers in patients with thyroid tumors and NENs. The role of PET imaging with different radiotracers in several endocrine tumors including thyroid tumors, gastroenteropancreatic neoplasms, lung neuroendocrine neoplasms, pheochromocytomas and paragangliomas, and multiple endocrine neoplasia syndromes has been described. Fluorine-18 fluorodeoxyglucose (18F-FDG) PET evaluating the glucose metabolism provides useful diagnostic and prognostic information in patients with thyroid tumors. Iodine-124 (124I) assessing the iodine metabolism may be used for dosimetry and diagnostic purposes in thyroid tumors. In patients with NENs specific radiotracers can be used for diagnostic purposes such as somatostatin analogues labeled with gallium-68 (68Ga-DOTA-peptides) evaluating somatostatin receptor expression and fluorine-18 fluorodihydroxyphenylalanine (18F-FDOPA) assessing the uptake, decarboxylation and storage of amine precursors. One advantage of 68Ga-DOTA-peptides PET is to select patients with well-differentiated and inoperable NENs for peptide receptor radionuclide therapy. 18F-FDG PET may provide useful prognostic information in patients with high-grade NENs. PET imaging with different radiotracers is a useful functional imaging technique in the work-up of several endocrine tumors.
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10.
Clinical guidance for radioiodine refractory differentiated thyroid cancer.
Gild, ML, Topliss, DJ, Learoyd, D, Parnis, F, Tie, J, Hughes, B, Walsh, JP, McLeod, DSA, Clifton-Bligh, RJ, Robinson, BG
Clinical endocrinology. 2018;(4):529-537
Abstract
Prognosis from differentiated thyroid cancer is worse when the disease becomes refractory to radioiodine. Until recently, treatment options have been limited to local therapies such as surgery and radiotherapy, but the recent availability of systemic therapies now provides some potential for disease control. Multitargeted kinase inhibitors (TKIs) including lenvatinib and sorafenib have been shown to improve progression-free survival in phase III clinical trials, but are also associated with a spectrum of adverse effects. Other TKIs have been utilized as "redifferentiation" agents, increasing sodium iodide symporter expression in metastases and thus restoring radioiodine avidity. Some patients whose disease progresses on initial TKI therapy will still respond to a different TKI and clinical trials currently in progress will clarify the best options for such patients. As these drugs are not inexpensive, care needs to be taken to minimize not only biological but also financial toxicity. In this review, we examine the basic biology of radioiodine refractory disease and discuss optimal treatment approaches, with specific focus on choice and timing of TKI treatment. This clinical field remains fluid, and directions for future research include exploring biomarkers and considering adjuvant TKI use in certain patient groups.