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RAI refractory thyroid cancer

Kyoungjune Pak, Seunghyeon Shin, Seong-Jang Kim, In-Joo Kim, Samuel Chang, Phillip Koo, Jennifer Kwak, Jae-Ho Kim
PURPOSE: The purpose of this study was to evaluate the response of retinoic acid (RA) in radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC). METHODS: Systematic searches of MEDLINE (from inception to December 2016) and of EMBASE (from inception to December 2016) were performed for English-language publications on thyroid cancer treated with RA. Studies were classified according to the response criteria used: (1) 123I or 131I whole body scintigraphy (WBS), (2) serum thyroglobulin (Tg) level, (3) the response evaluation criteria in solid tumors (RECIST) version 1...
2018: Oncology Research and Treatment
Ji Min Oh, Senthilkumar Kalimuthu, Prakash Gangadaran, Se Hwan Baek, Liya Zhu, Ho Won Lee, Ramya Lakshmi Rajendran, Chae Moon Hong, Shin Young Jeong, Sang-Woo Lee, Jaetae Lee, Byeong-Cheol Ahn
Radioactive-iodine (RAI) therapy is typically unprevailing as anaplastic thyroid cancer (ATC) management, owing to the decrease in the endogenous sodium iodide symporter (NIS) expression. Therefore, new strategies for NIS re-induction are required to improve the efficacy of RAI therapy in ATC. In this study, we developed a novel high-throughput NIS enhancer screening platform using a dual reporter gene system to identify a potent tyrosine kinase inhibitor (TKI) and selected a new hit compound, K905-0266 TKI...
January 23, 2018: Oncotarget
George E Naoum, Michael Morkos, Brian Kim, Waleed Arafat
Thyroid cancer is a frequently encountered endocrine malignancy. Despite the favorable prognosis of this disease, 15-20% of differentiated thyroid cancer (DTC) cases and most anaplastic types, remain resistant to standard treatment options, including radioactive iodine (RAI). In addition, around 30% of medullary thyroid cancer (MTC) cases show resistance after surgery. The evolving understanding of disease-specific molecular therapeutic targets has led to the approval of two targeted therapies (Sorafenib and Lenvatinib) for RAI refractory DTC and another two drugs (Vandetanib and Cabozantinib) for MTC...
February 19, 2018: Molecular Cancer
Mijin Kim, Tae Hyuk Kim, Dong Yeob Shin, Dong-Jun Lim, Eui Young Kim, Won Bae Kim, Jae Hoon Chung, YoungKee Shong, Bo Hyun Kim, Won Gu Kim
BACKGROUND: Sorafenib, a multi-kinase inhibitor, is approved for the treatment of patients with radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC). In this study, we evaluated the efficacy and safety of sorafenib in real-world clinical practice and compared the results with those of the DECISION trial. We also evaluated the clinical features associated with better clinical outcomes after sorafenib treatment. METHODS: This multicenter, retrospective cohort study evaluated 98 patients with progressive RAI-refractory DTC who were treated with sorafenib in six tertiary hospitals in Korea...
January 19, 2018: Thyroid: Official Journal of the American Thyroid Association
Catharina Balmelli, Nikola Railic, Marco Siano, Kristin Feuerlein, Richard Cathomas, Valerie Cristina, Christiane Güthner, Stefan Zimmermann, Sabine Weidner, Miklos Pless, Frank Stenner, Sacha I Rothschild
Purpose: Differentiated thyroid cancer (DTC) accounts for approximately 95% of thyroid carcinomas. In the metastatic RAI-refractory disease, chemotherapy has very limited efficacy and is associated with substantial toxicity. With increasing knowledge of the molecular pathogenesis of DTC, novel targeted therapies have been developed. Lenvatinib is a tyrosine kinase inhibitor (TKI) with promising clinical activity based on the randomized phase III SELECT trial. In Switzerland, a Named Patient Program (NPP) was installed to bridge the time gap to Swissmedic approval...
2018: Journal of Cancer
Thomas Artur Werner, Inga Nolten, Levent Dizdar, Jasmin Riemer, Sina Christin Schütte, Pablo Emilio Verde, Katharina Raba, Matthias Schott, Wolfram Trudo Knoefel, Andreas Krieg
Follicular thyroid cancer's (FTC) excellent long-term prognosis is mainly dependent on complete surgical removal and postoperative radioactive iodine (RAI) treatment. However, once the tumour becomes RAI refractory the 10-year disease specific survival rate drops below 10 %. The aim of our study was to evaluate the prognostic and biological role of the TRAIL system in FTC and to elucidate the influence of small molecule mediated antagonization of inhibitor of apoptosis proteins (IAPs) on TRAIL-sensitivity in vitro...
January 9, 2018: Endocrine-related Cancer
Marika H Tesselaar, Thomas Crezee, Imke Schuurmans, Danny Gerrits, James Nagarajah, Otto C Boerman, Ilse van Engen-van Grunsven, Johannes W A Smit, Romana T Netea-Maier, Theo S Plantinga
Purpose: Anaplastic thyroid cancer (ATC) is a rare malignancy that accounts for 1-2% of all thyroid cancers. ATC is one of the most aggressive human cancers, with rapid growth, tumor invasion and development of distant metastases. The median survival is only 5 months and the 1-year survival is less than 20%. Moreover, as a result of severe dedifferentiation including the loss of human sodium iodide symporter (hNIS) expression, radioactive iodide (RAI) therapy is ineffective. Recently, we have demonstrated beneficial effects of autophagy activating digitalis-like compounds (DLCs) on redifferentiation and concomitant restoration of iodide uptake in RAI-refractory papillary and follicular thyroid cancer cell lines...
December 14, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Yousuke Higuchi, Takayuki Motoki, Hisashi Ishida, Kiichiro Kanamitsu, Kana Washio, Takanori Oyama, Takuo Noda, Yasuko Tsurumaru, Ayumi Okada, Hirokazu Tsukahara, Akira Shimada
BACKGROUND: Pediatric papillary thyroid carcinoma frequently presents with lymph node involvement and distant metastases. Sorafenib, an oral multikinase inhibitor, has been used to treat radioactive iodine (RAI) therapy-refractory thyroid carcinoma in adults; however, pediatric experience is limited. Medical procedures and hospitalization for children with autism spectrum disorder may be challenging. CASE PRESENTATION: An 11-year-old boy with autism spectrum disorder and moderate intellectual impairment presented with dyspnea on exertion with thyroid carcinoma and diffuses lung metastases...
November 21, 2017: BMC Cancer
Francesco Felicetti, Alice Nervo, Alessandro Piovesan, Rita Berardelli, Filippo Marchisio, Marco Gallo, Emanuela Arvat
In the last decade tyrosine kinase inhibitors (TKIs) have been employed for a wide range of hematological and solid tumors and today they represent a valid therapeutic option for different neoplasms. Among them, both sorafenib and lenvatinib were approved for the treatment of radioactive iodine (RAI) refractory differentiated thyroid carcinoma (DTC). Unfortunately, in some cases the efficacy of TKIs is limited by the onset of drug resistance after the initial response. Areas covered: We report the case of a patient with a RAI refractory advanced DTC, treated with lenvatinib after surgery, multiple RAI administrations, traditional chemotherapy, and sorafenib...
December 2017: Expert Review of Anticancer Therapy
Marika H Tesselaar, Jan Wa Smit, James Nagarajah, Romana T Netea-Maier, Theo S Plantinga
Whereas in most patients with non-medullary thyroid cancer (TC) disease remission is achieved by thyroidectomy and ablation of tumor remnants by radioactive iodide (RAI), a substantial subgroup of patients with metastatic disease present tumor lesions that have acquired RAI resistance as a result of dedifferentiation. Although oncogenic mutations in BRAF, TERT promoter and TP53 are associated with an increased propensity for induction of dedifferentiation, the role of genetic and epigenetic aberrations and their effects on important intracellular signaling pathways is not yet fully elucidated...
September 20, 2017: Journal of Molecular Endocrinology
Peng Cheng, Brynn Hollingsworth, Daniel Scarberry, Daniel H Shen, Kimerly Powell, Sean C Smart, John Beech, Xiaochao Sheng, Lawrence S Kirschner, Chia-Hsiang Menq, Sissy M Jhiang
BACKGROUND: The ability of thyroid follicular cells to take up iodine enables the use of radioactive iodine (RAI) for imaging and targeted killing of RAI-avid thyroid cancer following thyroidectomy. To facilitate identifying novel strategies to improve (131)I therapeutic efficacy for patients with RAI refractory disease, it is desired to optimize image acquisition and analysis for preclinical mouse models of thyroid cancer. METHODS: A customized mouse cradle was designed and used for microSPECT/CT image acquisition at 1 hour (t1) and 24 hours (t24) post injection of (123)I, which mainly reflect RAI influx/efflux equilibrium and RAI retention in the thyroid, respectively...
November 2017: Thyroid: Official Journal of the American Thyroid Association
Furio Pacini
Distant metastases from differentiated thyroid cancer (DTC) are a rare event, occurring in less than 10% of patients with persistent or recurrent clinical disease. About 50% of these patients do respond to radioiodine (RAI) therapy, either with complete remission or stabilization of the disease on a long term period. Unfortunately, another 50% of these patients are refractory to the treatment with RAI, either from the first appearance of distant metastases or during follow-up. Overall, these patients represent 4-5 new cases/year/million...
June 2017: Best Practice & Research. Clinical Endocrinology & Metabolism
Dan Mei, Bin Lv, Bo Chen, Shan Xiao, Jie Jiang, Yan Xie, Ling Jiang
Recently, diagnoses of radioiodine-refractory differentiated thyroid cancer (RAI-R DTC) have become more common; prognosis is poor. It has been suggested that cancer stem cells account for radiotherapy resistance. By flow cytometry, different expression percents of CD133 and OCT4 in thyroid cancer cell lines were detected. By real-time quantitative PCR, different mRNA expression of CD133, OCT4, GLUT1, thyroglobulin (TG), thyroperoxidase (TPO) and sodium iodine symporter (NIS) was analyzed; the localization of CD133, OCT4, and NIS expression was examined using immunofluorescence confocal microscopy...
2017: PloS One
Maria E Cabanillas, Jonas A de Souza, Susan Geyer, Lori J Wirth, Michael E Menefee, Stephen V Liu, Komal Shah, John Wright, Manisha H Shah
Purpose Sorafenib and lenvatinib are oral multikinase inhibitors targeting vascular endothelial growth factor receptor (VEGFR) and approved for radioiodine (RAI)-refractory differentiated thyroid cancer (DTC). However, there are no approved second- or third-line therapies. MET is implicated in resistance to VEGFR inhibitors. Cabozantinib is an oral multikinase inhibitor targeting MET in addition to VEGFR and is approved for medullary thyroid cancer. In a phase I study of cabozantinib, five of eight patients with DTC previously treated with a VEGFR-targeted therapy had an objective response to cabozantinib...
October 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Chen Wang, Xin Zhang, Hui Li, Xin Li, Yansong Lin
OBJECTIVE: Current diagnosis of radioactive iodine (RAI)-refractory (RAIR) differentiated thyroid cancer (DTC) is based on the imaging technique, which is of a high cost. Serum thyroglobulin (Tg) is a sensitive and easily obtained biomarker. Hence, we aimed to assess the predicting value of quantitative response of Tg in earlier identifying the RAIR-DTC with pulmonary metastasis. PATIENTS AND METHODS: Pulmonary metastatic DTC patients who underwent total or near-total thyroidectomy and at least two times of RAI therapy were included in this study...
2017: PloS One
Jaume Capdevila, José Manuel Trigo, Javier Aller, José Luís Manzano, Silvia García Adrián, Carles Zafón Llopis, Òscar Reig, Uriel Bohn, Teresa Ramón Y Cajal, Manuel Duran-Poveda, Beatriz González Astorga, Ana López-Alfonso, Javier Medina Martínez, Ignacio Porras, Juan Jose Reina, Nuria Palacios, Enrique Grande, Elena Cillán, Ignacio Matos, Juan Jose Grau
BACKGROUND: Axitinib, an antiangiogenic multikinase inhibitor (MKI), was evaluated in the compassionate use programme (CUP) in Spain (October 2012-November 2014). SUBJECTS AND METHODS: 47 patients with advanced radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC, n = 34) or medullary thyroid cancer (MTC, n = 13) with documented disease progression were treated with axitinib 5 mg b.i.d. The primary efficacy endpoint was objective response rate (ORR) by Response Evaluation Criteria In Solid Tumors (RECIST) v1...
October 2017: European Journal of Endocrinology
J R Cracchiolo, R J Wong
Lateral neck lymph node metastases in well differentiated thyroid cancer are common, ranging from 30% to 60%, with the majority of these foci identifiable only as microscopic deposits. A skilled ultrasound evaluation of the lymph nodes in the lateral neck is recommended for all patients presenting with newly diagnosed thyroid cancer undergoing surgical management. Ultrasound guided fine needle aspiration biopsy may be used to cytologically confirm suspected lateral neck nodal metastases prior to surgery. For patients with large volume nodal disease, extranodal extension, or multiple nodal metastases, computed tomography (CT) scan of the neck with contrast is an important additional imaging modality to accurately localize disease prior to surgery...
June 22, 2017: European Journal of Surgical Oncology
Naomi Kiyota, Bruce Robinson, Manisha Shah, Ana O Hoff, Matthew H Taylor, Di Li, Corina E Dutcus, Eun Kyung Lee, Sung-Bae Kim, Makoto Tahara
BACKGROUND: While there is a clear consensus for defining radioiodine-refractory differentiated thyroid cancer (RR-DTC), it is unknown whether these criteria are equally valid for determining when radioiodine (RAI) therapy is no longer beneficial and systemic treatment should be considered. Lenvatinib, a multikinase inhibitor, significantly prolonged progression-free survival (PFS) compared to placebo in a Phase 3 trial in RR-DTC (SELECT; hazard ratio [HR]: 0.21 [99% confidence interval (CI) 0...
September 2017: Thyroid: Official Journal of the American Thyroid Association
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 differentiated thyroid cancer (DTC). An uncontrolled, open-label, multicenter, single-arm, Phase 2 clinical study was conducted to evaluate the safety and efficacy of sorafenib in Japanese patients with MTC and ATC...
September 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
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