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RAI refractory thyroid cancer

Yasuhiro Ito, Naoyoshi Onoda, Ken-Ichi Ito, Iwao Sugitani, Shunji Takahashi, Iku Yamaguchi, Koki Kabu, Katsuya Tsukada
BACKGROUND: Therapeutic options for treating advanced or metastatic medullary thyroid carcinoma (MTC) and anaplastic thyroid carcinoma (ATC) are still limited in Japan even though vandetanib for MTC, and lenvatinib for MTC and ATC have been approved. Sorafenib is an oral multikinase inhibitor approved for the treatment of patients with radioactive iodine-refractory (RAI-R) differentiated thyroid cancer (DTC). We conducted an uncontrolled, open-label, multicenter, single-arm, phase 2 clinical study to evaluate the safety and efficacy of sorafenib in Japanese patients with MTC and ATC...
June 21, 2017: Thyroid: Official Journal of the American Thyroid Association
L Valerio, L Pieruzzi, C Giani, L Agate, V Bottici, L Lorusso, V Cappagli, L Puleo, A Matrone, D Viola, C Romei, R Ciampi, E Molinaro, R Elisei
Thyroid cancer typically has a good outcome following standard treatments, which include surgery, radioactive iodine ablation for differentiated tumours and treatment with thyrotropine hormone-suppressive levothyroxine. Thyroid cancers that persist or recur following these therapies have a poorer prognosis. Cytotoxic chemotherapy or external beam radiotherapy has a low efficacy in these patients. 'Target therapy' with tyrosine kinase inhibitors (TKIs) represent an important therapeutic option for the treatment of advanced cases of radioiodine refractory (RAI-R) differentiated thyroid cancer (DTC), medullary thyroid cancer (MTC) and possibly for cases of poorly differentiated (PDTC) and anaplastic thyroid cancer (ATC)...
May 2017: Clinical Oncology: a Journal of the Royal College of Radiologists
Angelica Schmidt, Laura Iglesias, Michele Klain, Fabián Pitoia, Martin J Schlumberger
Radioiodine (RAI)-refractory thyroid cancer is an uncommon entity, occurring with an estimated incidence of 4-5 cases/year/million people. RAI refractoriness is more frequent in older patients, in those with large metastases, in poorly differentiated thyroid cancer, and in those tumors with high 18-fluordeoxyglucose uptake on PET/CT. These patients have a 10-year survival rate of less than 10%. In recent years, new therapeutic agents with molecular targets have become available, with multikinase inhibitors (MKIs) being the most investigated drugs...
January 2017: Archives of Endocrinology and Metabolism
Morimasa Kitamura, Tomomasa Hayashi, Chiaki Suzuki, Shigeru Hirano, Ichiro Tateya, Yo Kishimoto, Koichi Omori
BACKGROUND: There are currently no effective therapeutic methods for locally recurrent, metastatic, or progressive radioactive iodine (RAI)-refractory differentiated thyroid cancer. However, multitargeted tyrosine kinase inhibitors (TKIs) such as lenvatinib or sorafenib have been approved for patients with RAI-refractory differentiated thyroid cancer as a second targeted therapy, and these agents can prolong patient survival. However, several cases have been reported that TKIs have caused fatal complications such as fistula formation or bleeding...
January 14, 2017: World Journal of Surgical Oncology
Marika H Tesselaar, Thomas Crezee, Herman G Swarts, Danny Gerrits, Otto C Boerman, Jan B Koenderink, Hendrik G Stunnenberg, Mihai G Netea, Johannes W A Smit, Romana T Netea-Maier, Theo S Plantinga
Up to 20%-30% of patients with metastatic non-medullary thyroid cancer have persistent or recurrent disease resulting from tumor dedifferentiation. Tumor redifferentiation to restore sensitivity to radioactive iodide (RAI) therapy is considered a promising strategy to overcome RAI resistance. Autophagy has emerged as an important mechanism in cancer dedifferentiation. Here, we demonstrate the therapeutic potential of autophagy activators for redifferentiation of thyroid cancer cell lines. Five autophagy-activating compounds, all known as digitalis-like compounds, restored hNIS expression and iodide uptake in thyroid cancer cell lines...
January 2017: Molecular Cancer Therapeutics
Pawel Kawalec, Iwona Malinowska-Lipień, Tomasz Brzostek, Maria Kózka
Thyroid carcinoma is the most prevalent endocrine malignancy, with an increasing incidence over the past decades. Treatment of differentiated thyroid cancer consists of surgery followed by radioactive iodine (RAI) ablation of the thyroid remnant, and TSH suppression. Among new therapeutic solutions for patients with advanced RR-DTC stage, the most promising seem to be sorafenib and lenvatinib, up to now considered to be orphan drugs. Areas covered: We performed a systematic review of medical databases to collect all eligible clinical trials referring to the topic of our analysis...
December 2016: Expert Review of Anticancer Therapy
J Capdevila, J C Galofré, E Grande, C Zafón Llopis, T Ramón Y Cajal Asensio, E Navarro González, P Jiménez-Fonseca, J Santamaría Sandi, J M Gómez Sáez, G Riesco Eizaguirre
Thyroid cancer is the single most prevalent endocrine malignancy; differentiated thyroid cancer (DTC) accounts for more than 90 % of all malignancies and its incidence has been rising steadily. For more patients, surgical treatment, radioactive iodine (RAI) ablation, and thyroid-stimulating hormone (TSH) suppressive therapy achieve an overall survival (OS) rate of 97.7 % at 5 years. Nevertheless, locoregional recurrence occurs in up to 20 % and distant metastases in approximately 10 % at 10 years. Two-thirds of these patients will never be cured with radioactive iodine therapy and will become RAI-refractory, with a 3-year OS rate of less than 50 %...
March 2017: Clinical & Translational Oncology
Tatiana Kelil, Abhishek R Keraliya, Stephanie A Howard, Katherine M Krajewski, Marta Braschi-Amirfarzan, Jason L Hornick, Nikhil H Ramaiya, Sree Harsha Tirumani
Substantial improvement in the understanding of the oncogenic pathways in thyroid cancer has led to identification of specific molecular alterations, including mutations of BRAF and RET in papillary thyroid cancer, mutation of RAS and rearrangement of PPARG in follicular thyroid cancer, mutation of RET in medullary thyroid cancer, and mutations of TP53 and in the phosphatidylinositol 3'-kinase (PI3K)/AKT1 pathway in anaplastic thyroid cancer. Ultrasonography (US) and US-guided biopsy remain cornerstones in the initial workup of thyroid cancer...
September 2016: Radiographics: a Review Publication of the Radiological Society of North America, Inc
Katharina Mischler, Stefan Kneifel, Richard Cathomas
BACKGROUND: Metastatic differentiated thyroid cancer (DTC) is a rare disease that is in the first line treated with iodine-131 radioisotope therapy. Until recently, options were very limited in the case of progressive radioactive-iodine (RAI)-refractory disease. Based on new study results, tyrosine kinase inhibitors (TKIs) have attracted attention. The TKI sorafenib demonstrated significantly improved progression-free survival (PFS) in a phase III trial. Recent data from another phase III trial showed that the TKI lenvatinib achieved high response rates and a large improvement in PFS in metastatic RAI-refractory DTC patients in the first-line setting and after 1 prior line of TKI...
2016: Oncology Research and Treatment
Xue Yang, Jiao Li, Xiaoyi Li, Zhiyong Liang, Wen Gao, Jun Liang, Shujun Cheng, Yansong Lin
Telomerase reverse transcriptase (TERT) promoter mutation has been reported to be associated with aggressive characteristics in differentiated thyroid cancer (DTC). This study examined the status of TERT mutation in distant metastatic DTC and evaluated the correlation between TERT mutation and radioiodine uptake, as well as that between TERT mutation and therapy response. METHODS: TERT promoter and B-Raf proto-oncogene (BRAF) V600E mutation were retrospectively examined in primary tumors of 66 patients with distant metastatic DTC...
February 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Sandip Basu, Rahul Vithalrao Parghane
The process of radioiodine ((131)I) refractoriness, dedifferentiation, and development of thyroglobulin elevation and negative iodine scintigraphy (TENIS) syndrome in metastatic differentiated thyroid carcinoma (DTC) could be viewed as a disease continuum rather than a single event or an all-or-none phenomenon. In this report, the important role of molecular functional imaging in systematically exploring the disease biology and course of metastatic DTC is presented. Making this role the base, this report proposes a novel clinical classification for TENIS syndrome using molecular functional imaging...
September 2016: Journal of Nuclear Medicine Technology
Jolanta Krajewska, Aleksandra Kukulska, Barbara Jarzab
INTRODUCTION: Radioiodine [RAI]-resistant advanced and progressive differentiated thyroid cancer [DTC], although rare, constitutes a real challenge as its prognosis is poor and available therapeutic options, until now, have been limited. Discovery of a crucial role of distinct tyrosine kinases in DTC pathogenesis opened up new options in systemic treatment. Lenvatinib is an oral potent multi kinase inhibitor [MKI] of different growth factor receptors including VEGFR1/Flt-1, VEGFR2/KDR, VEGFR3, FGFR1,2,3,4, PDGFR-β as well as RET and KIT signaling networks...
August 2016: Expert Opinion on Pharmacotherapy
Athanasios Bikas, Shivangi Vachhani, Kirk Jensen, Vasyl Vasko, Kenneth D Burman
Introduction Patients with progressive, metastatic, RAI-refractory differentiated thyroid cancer (DTC), as well as patients with advanced medullary (MTC) and anaplastic thyroid cancer represent a cohort for which therapeutic options are limited. The recent discoveries in the molecular mechanisms implicated in TC have provided insight of the pathogenesis and progression of disease. In that respect, targeted therapies have emerged as a promising alternative for the treatment of those patients. Areas Covered Tyrosine Kinase Inhibitors (TKIs) have been studied extensively in TC: sorafenib and lenvatinib have been approved by the FDA for the treatment of metastatic, RAI-refractory DTC, while vandetanib and cabozantinib are FDA approved for use in advanced MTC...
July 1, 2016: Expert Review of Clinical Pharmacology
Andrew G Gianoukakis, Natalia M Flores, Corey L Pelletier, Anna Forsythe, Gregory R Wolfe, Matthew H Taylor
BACKGROUND: Patients with differentiated thyroid cancer (DTC) often respond well to treatment but some become refractory to radioactive iodine (RAI) treatment, and treatment options are limited. Despite the humanistic and economic burden RAI refractory disease imposes on patients, published research concerning treatment patterns and health care resource utilization is sparse. METHODS: Data were collected from an online retrospective chart review study in the US and five European Union (EU) countries (France, Germany, Italy, Spain, and UK) with physicians recruited from an online panel...
2016: Cancer Management and Research
Rasmus Laursen, Markus Wehland, Sascha Kopp, Jessica Pietsch, Manfred Infanger, Jirka Grosse, Daniela Grimm
BACKGROUND: Thyroid cancer is the most common type of endocrine neoplasia. Differentiated thyroid carcinoma (DTC) represents 94% of all thyroid cancer types. Approximately 20% experience local recurrence and 10% distant metastasis. The recurrent DTC often becomes less differentiated, loses the iodine uptake capability and consequently loses the radioactive iodine treatment option. Under these circumstances survivability drops below 10% at 10 years. The treatment options for dedifferentiated thyroid cancers are extremely limited...
June 13, 2016: Current Pharmaceutical Design
Yasuhiro Ito, Shinichi Suzuki, Ken-Ichi Ito, Tsuneo Imai, Takahiro Okamoto, Hiroya Kitano, Iwao Sugitani, Kiminori Sugino, Hidemitsu Tsutsui, Hisato Hara, Akira Yoshida, Kazuo Shimizu
Differentiated thyroid carcinoma (DTC) is generally indolent in nature and, even though it metastasizes to distant organs, the prognosis is normally excellent. In contrast, the overall survival (OS) of patients with radioactive iodine (RAI)-refractory and progressive metastases is dire, because no effective therapies have been available to control the metastatic lesions. However, recently, administration of tyrosine-kinase inhibitors (TKIs) has become a new line of therapy for RAI-refractory and progressive metastases...
July 30, 2016: Endocrine Journal
David Viola, Laura Valerio, Eleonora Molinaro, Laura Agate, Valeria Bottici, Agnese Biagini, Loredana Lorusso, Virginia Cappagli, Letizia Pieruzzi, Carlotta Giani, Elena Sabini, Paolo Passannati, Luciana Puleo, Antonio Matrone, Benedetta Pontillo-Contillo, Valentina Battaglia, Salvatore Mazzeo, Paolo Vitti, Rossella Elisei
Thyroid cancer is rare, but it is the most frequent endocrine malignancy. Its prognosis is generally favorable, especially in cases of well-differentiated thyroid cancers (DTCs), such as papillary and follicular cancers, which have survival rates of approximately 95% at 40 years. However, 15-20% of cases became radioiodine refractory (RAI-R), and until now, no other treatments have been effective. The same problems are found in cases of poorly differentiated (PDTC) and anaplastic (ATC) thyroid cancers and in at least 30% of medullary thyroid cancer (MTC) cases, which are very aggressive and not sensitive to radioiodine...
April 2016: Endocrine-related Cancer
Sujata Narayanan, A Dimitrios Colevas
Radioiodine refractory differentiated thyroid cancer (RAI-R DTC) is a challenging malignancy with limited prognosis and treatment options. Recently, clinical trials with targeted therapies have advanced the outlook of these patients, and inhibition of the vascular endothelial growth factor (VEGF) axis has led to the approval of small-molecule tyrosine kinase inhibitors (TKIs) for first-line treatment of radioiodine refractory disease. In addition to approved therapies (sorafenib and lenvatinib), other multi-targeted tyrosine kinase inhibitors that are commercially available have been recognized as viable treatment options for RAI-R DTC...
June 2016: Current Treatment Options in Oncology
Alexis Vrachimis, Lars Stegger, Christian Wenning, Benjamin Noto, Matthias Christian Burg, Julia Renate Konnert, Thomas Allkemper, Walter Heindel, Burkhard Riemann, Michael Schäfers, Matthias Weckesser
PURPOSE: The purpose of this study was to determine whether [(68)Ga]DOTATATE PET/MRI with diffusion-weighted imaging (DWI) can replace or complement [(18)F]FDG PET/CT in patients with radioactive-iodine (RAI)-refractory differentiated thyroid cancer (DTC). METHODS: The study population comprised 12 patients with elevated thyroglobulin and a negative RAI scan after thyroidectomy and RAI remnant ablation who underwent both [(18)F]FDG PET/CT and [(68)Ga]DOTATATE PET/MRI within 8 weeks of each other...
September 2016: European Journal of Nuclear Medicine and Molecular Imaging
Mona M Sabra, Ronald Ghossein, R Michael Tuttle
BACKGROUND: With the advent of molecular targeted therapy for the management of radioactive iodine (RAI) refractory, progressive metastatic thyroid cancer, it becomes important to define the time course and risk factors for structural disease progression in follicular cell-derived thyroid cancer (FCDTC) patients. This will help in defining the optimal time to start these therapies and better define their impact on structural disease progression. OBJECTIVES: This retrospective review of 199 consecutive patients with FCDTC presenting with lung metastasis examined the progression-free survival (PFS) in thyroid cancer patients with lung metastasis treated with surgery and RAI, and who had not received molecular targeted therapy or chemotherapy...
April 2016: Thyroid: Official Journal of the American Thyroid Association
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