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Chen Wang Department of Nuclear Medicine, Peking Union Medical College Hospital, Beijing, China
Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing, China

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Xin Zhang Department of Nuclear Medicine, Peking Union Medical College Hospital, Beijing, China
Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing, China

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Xue Yang Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, China

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Hui Li Department of Nuclear Medicine, Peking Union Medical College Hospital, Beijing, China
Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing, China

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Ruixue Cui Department of Nuclear Medicine, Peking Union Medical College Hospital, Beijing, China
Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing, China

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Wenmin Guan Department of Radiology, Peking Union Medical College Hospital, Beijing, China

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Xin Li Department of Nuclear Medicine, Zhejiang Cancer Hospital, Hangzhou, China

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Zhaohui Zhu Department of Nuclear Medicine, Peking Union Medical College Hospital, Beijing, China
Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing, China

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Yansong Lin Department of Nuclear Medicine, Peking Union Medical College Hospital, Beijing, China
Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing, China

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. Journal of Nuclear Medicine 58 258 – 265 . ( https://doi.org/10.2967/jnumed.116.180240 ) 10.2967/jnumed.116.180240 Zhao D Jin X Li F Liang J Lin Y 2012 Integrin alphavbeta3 imaging of radioactive iodine-refractory thyroid cancer using 99 mTc-3

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Ana Albero Department of Oncology, Andalusian Agency for Health Technology Assessment (AETSA), Department of Endocrinology and Nutrition, University Hospital ‘Virgen Macarena’, Seville, Spain

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Juliana Ester Lopéz Department of Oncology, Andalusian Agency for Health Technology Assessment (AETSA), Department of Endocrinology and Nutrition, University Hospital ‘Virgen Macarena’, Seville, Spain

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Alberto Torres Department of Oncology, Andalusian Agency for Health Technology Assessment (AETSA), Department of Endocrinology and Nutrition, University Hospital ‘Virgen Macarena’, Seville, Spain

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Luis de la Cruz Department of Oncology, Andalusian Agency for Health Technology Assessment (AETSA), Department of Endocrinology and Nutrition, University Hospital ‘Virgen Macarena’, Seville, Spain

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Tomas Martín Department of Oncology, Andalusian Agency for Health Technology Assessment (AETSA), Department of Endocrinology and Nutrition, University Hospital ‘Virgen Macarena’, Seville, Spain

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In differentiated thyroid carcinoma refractory to radioactive iodine (CDT-RTI), chemotherapy has been considered for decades to be the only systemic therapy with palliative purpose. Phase II studies assessing the efficacy of different chemotherapy outlines have been published. Nevertheless, phase III studies in these tumours have not been performed. Our objective is to evaluate the effectiveness of chemotherapy in patients with CDT-RTI by a systematic review of published studies. Systematic research of the literature in Medline and Embase databases (among others) was carried out. The full texts of selected references were analysed by two independent reviewers and then assessed for risk of bias in each study. We also extracted data using specifically designed questionnaires. Later, a qualitative synthesis of results was performed and pooled data were calculated. We found that 16 studies with 473 patients published in the last 40 years were included out of 509 identified references in databases. Thirteen studies (176 patients) included data on response to treatment and histology. Four studies included 70 patients only with well-differentiated non-medullary tumours. Response rate (RR) was 22.1% (0–57%) for 13 studies, 25% for the 176 patients and 27.1% for the 70 patients, with 2.5, 3.4 and 2.8% complete responses respectively. Survival times could not be assessed or pooled due to the lack of data and heterogeneity of the studies, and was determined to have a high risk of bias. Although it has not been possible to find solid evidence about the efficacy of chemotherapy, the results shown indicate that it may have some effectiveness, although this should be proven with well-designed studies using modern drugs.

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Peter M Sadow Department of Pathology, WRN219, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts, 02114, USA
Department of Pathology, WRN219, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts, 02114, USA

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Dora Dias-Santagata Department of Pathology, WRN219, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts, 02114, USA

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Zongli Zheng Department of Pathology, WRN219, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts, 02114, USA

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Derrick T Lin Department of Pathology, WRN219, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts, 02114, USA

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Long Phi Le Department of Pathology, WRN219, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts, 02114, USA

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Carmelo Nucera Department of Pathology, WRN219, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts, 02114, USA

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Mutational profile of advanced primary and metastatic radioactive iodine-refractory thyroid cancers reveals distinct pathogenetic roles for BRAF, PIK3CA, and AKT1 . Cancer Research 69 4885 – 4893 . ( doi:10.1158/0008-5472.CAN-09-0727 ). Rosove MH Peddi

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Camille Buffet Sorbonne Université, Unité Thyroïde-Tumeurs endocrine, Groupe de Recherche Clinique n°16 Tumeurs Thyroïdiennes, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France

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Johanna Wassermann Sorbonne Université, Service d’Oncologie, Groupe de Recherche Clinique n°16 Tumeurs Thyroïdiennes, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France

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Fabio Hecht Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, UFRJ, Rio de Janeiro, Brazil

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Laurence Leenhardt Sorbonne Université, Unité Thyroïde-Tumeurs endocrine, Groupe de Recherche Clinique n°16 Tumeurs Thyroïdiennes, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France

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Corinne Dupuy UMR 8200 CNRS, Villejuif, France
Université Paris-Saclay et Gustave Roussy, Villejuif, France

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Lionel Groussin INSERM Unité 1016, CNRS, UMR 8104, Institut Cochin, Paris, France
Université de Paris, Paris, France
Department of Endocrinology, APHP, Cochin Hospital, Paris, France

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Charlotte Lussey-Lepoutre Sorbonne Université, Service de Médecine Nucléaire, Groupe de Recherche Clinique n°16 Tumeurs Thyroïdiennes, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France
PARCC, INSERM, Equipe Labellisée par la Ligue contre le Cancer, Paris, France

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) Pak K Shin S Kim SJ Kim IJ Chang S Koo P Kwak J Kim JH 2018 Response of retinoic acid in patients with radioactive iodine-refractory thyroid cancer: a meta-analysis . Oncology Research and Treatment 41 100 – 104 . ( https

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D Deandreis Department of Nuclear Medicine and Endocrine Oncology, Department of Pathology and Clinical Biology, Unit 605, National Institute of Health and Medical Research, Institut Gustave Roussy and University Paris Sud, 39 Rue Camille Desmoulins, 94805 Villejuif, France

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A Al Ghuzlan Department of Nuclear Medicine and Endocrine Oncology, Department of Pathology and Clinical Biology, Unit 605, National Institute of Health and Medical Research, Institut Gustave Roussy and University Paris Sud, 39 Rue Camille Desmoulins, 94805 Villejuif, France

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S Leboulleux Department of Nuclear Medicine and Endocrine Oncology, Department of Pathology and Clinical Biology, Unit 605, National Institute of Health and Medical Research, Institut Gustave Roussy and University Paris Sud, 39 Rue Camille Desmoulins, 94805 Villejuif, France

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L Lacroix Department of Nuclear Medicine and Endocrine Oncology, Department of Pathology and Clinical Biology, Unit 605, National Institute of Health and Medical Research, Institut Gustave Roussy and University Paris Sud, 39 Rue Camille Desmoulins, 94805 Villejuif, France

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J P Garsi Department of Nuclear Medicine and Endocrine Oncology, Department of Pathology and Clinical Biology, Unit 605, National Institute of Health and Medical Research, Institut Gustave Roussy and University Paris Sud, 39 Rue Camille Desmoulins, 94805 Villejuif, France

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M Talbot Department of Nuclear Medicine and Endocrine Oncology, Department of Pathology and Clinical Biology, Unit 605, National Institute of Health and Medical Research, Institut Gustave Roussy and University Paris Sud, 39 Rue Camille Desmoulins, 94805 Villejuif, France

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J Lumbroso Department of Nuclear Medicine and Endocrine Oncology, Department of Pathology and Clinical Biology, Unit 605, National Institute of Health and Medical Research, Institut Gustave Roussy and University Paris Sud, 39 Rue Camille Desmoulins, 94805 Villejuif, France

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E Baudin Department of Nuclear Medicine and Endocrine Oncology, Department of Pathology and Clinical Biology, Unit 605, National Institute of Health and Medical Research, Institut Gustave Roussy and University Paris Sud, 39 Rue Camille Desmoulins, 94805 Villejuif, France

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B Caillou Department of Nuclear Medicine and Endocrine Oncology, Department of Pathology and Clinical Biology, Unit 605, National Institute of Health and Medical Research, Institut Gustave Roussy and University Paris Sud, 39 Rue Camille Desmoulins, 94805 Villejuif, France

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J M Bidart Department of Nuclear Medicine and Endocrine Oncology, Department of Pathology and Clinical Biology, Unit 605, National Institute of Health and Medical Research, Institut Gustave Roussy and University Paris Sud, 39 Rue Camille Desmoulins, 94805 Villejuif, France

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M Schlumberger Department of Nuclear Medicine and Endocrine Oncology, Department of Pathology and Clinical Biology, Unit 605, National Institute of Health and Medical Research, Institut Gustave Roussy and University Paris Sud, 39 Rue Camille Desmoulins, 94805 Villejuif, France

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D Knauf JA Tuttle RM 2009 Mutational profile of advanced primary and metastatic radioactive iodine-refractory thyroid cancer reveals distinct pathogenetic roles of BRAF, PIK3CA and AKT1 . Cancer Research 69 4885 – 4893 doi:10

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Devora Champa
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Marika A Russo
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Xiao-Hui Liao Department of Developmental and Molecular Biology, Departments of Medicine, Pediatrics and Committee on Genetics, Department of Pathology, Albert Einstein College of Medicine, Price Center for Genetic and Translational Medicine, 1301 Morris Park Avenue, Room 302, Bronx, New York 10461, USA

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Samuel Refetoff Department of Developmental and Molecular Biology, Departments of Medicine, Pediatrics and Committee on Genetics, Department of Pathology, Albert Einstein College of Medicine, Price Center for Genetic and Translational Medicine, 1301 Morris Park Avenue, Room 302, Bronx, New York 10461, USA
Department of Developmental and Molecular Biology, Departments of Medicine, Pediatrics and Committee on Genetics, Department of Pathology, Albert Einstein College of Medicine, Price Center for Genetic and Translational Medicine, 1301 Morris Park Avenue, Room 302, Bronx, New York 10461, USA

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Ronald A Ghossein Department of Developmental and Molecular Biology, Departments of Medicine, Pediatrics and Committee on Genetics, Department of Pathology, Albert Einstein College of Medicine, Price Center for Genetic and Translational Medicine, 1301 Morris Park Avenue, Room 302, Bronx, New York 10461, USA

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Antonio Di Cristofano
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500 – 501 . ( doi:10.1038/ng0506-500 ). Ricarte-Filho JC Ryder M Chitale DA Rivera M Heguy A Ladanyi M Janakiraman M Solit D Knauf JA Tuttle RM 2009 Mutational profile of advanced primary and metastatic radioactive iodine-refractory

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Gahee Park Samsung Genome Institute, Internal Medicine, Surgery, Biomedical Sciences, Department of Internal Medicine, Department of Molecular Cell Biology, Samsung Medical Center, 50 Irwondong, Gangnamgu, Seoul 135-710, Korea Departments of
Samsung Genome Institute, Internal Medicine, Surgery, Biomedical Sciences, Department of Internal Medicine, Department of Molecular Cell Biology, Samsung Medical Center, 50 Irwondong, Gangnamgu, Seoul 135-710, Korea Departments of

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Tae Hyuk Kim Samsung Genome Institute, Internal Medicine, Surgery, Biomedical Sciences, Department of Internal Medicine, Department of Molecular Cell Biology, Samsung Medical Center, 50 Irwondong, Gangnamgu, Seoul 135-710, Korea Departments of

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Hae-Ock Lee Samsung Genome Institute, Internal Medicine, Surgery, Biomedical Sciences, Department of Internal Medicine, Department of Molecular Cell Biology, Samsung Medical Center, 50 Irwondong, Gangnamgu, Seoul 135-710, Korea Departments of

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Jung Ah Lim Samsung Genome Institute, Internal Medicine, Surgery, Biomedical Sciences, Department of Internal Medicine, Department of Molecular Cell Biology, Samsung Medical Center, 50 Irwondong, Gangnamgu, Seoul 135-710, Korea Departments of
Samsung Genome Institute, Internal Medicine, Surgery, Biomedical Sciences, Department of Internal Medicine, Department of Molecular Cell Biology, Samsung Medical Center, 50 Irwondong, Gangnamgu, Seoul 135-710, Korea Departments of

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Jae-Kyung Won Samsung Genome Institute, Internal Medicine, Surgery, Biomedical Sciences, Department of Internal Medicine, Department of Molecular Cell Biology, Samsung Medical Center, 50 Irwondong, Gangnamgu, Seoul 135-710, Korea Departments of

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Hye Sook Min Samsung Genome Institute, Internal Medicine, Surgery, Biomedical Sciences, Department of Internal Medicine, Department of Molecular Cell Biology, Samsung Medical Center, 50 Irwondong, Gangnamgu, Seoul 135-710, Korea Departments of

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Kyu Eun Lee Samsung Genome Institute, Internal Medicine, Surgery, Biomedical Sciences, Department of Internal Medicine, Department of Molecular Cell Biology, Samsung Medical Center, 50 Irwondong, Gangnamgu, Seoul 135-710, Korea Departments of

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Do Joon Park Samsung Genome Institute, Internal Medicine, Surgery, Biomedical Sciences, Department of Internal Medicine, Department of Molecular Cell Biology, Samsung Medical Center, 50 Irwondong, Gangnamgu, Seoul 135-710, Korea Departments of

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Young Joo Park Samsung Genome Institute, Internal Medicine, Surgery, Biomedical Sciences, Department of Internal Medicine, Department of Molecular Cell Biology, Samsung Medical Center, 50 Irwondong, Gangnamgu, Seoul 135-710, Korea Departments of

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Woong-Yang Park Samsung Genome Institute, Internal Medicine, Surgery, Biomedical Sciences, Department of Internal Medicine, Department of Molecular Cell Biology, Samsung Medical Center, 50 Irwondong, Gangnamgu, Seoul 135-710, Korea Departments of
Samsung Genome Institute, Internal Medicine, Surgery, Biomedical Sciences, Department of Internal Medicine, Department of Molecular Cell Biology, Samsung Medical Center, 50 Irwondong, Gangnamgu, Seoul 135-710, Korea Departments of
Samsung Genome Institute, Internal Medicine, Surgery, Biomedical Sciences, Department of Internal Medicine, Department of Molecular Cell Biology, Samsung Medical Center, 50 Irwondong, Gangnamgu, Seoul 135-710, Korea Departments of

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supports the molecular phenotype-stratified approach to cancer care ( Willyard 2013 ). In patients with radioactive-iodine-refractory thyroid cancer, the use of practical diagnostic methodology such as IHC to identify patients with rearrangements of ALK

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Marie-Claude Hofmann Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas MD Anderson Cancer Center, Houston, Texas, USA

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Muthusamy Kunnimalaiyaan Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas MD Anderson Cancer Center, Houston, Texas, USA

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Jennifer R Wang Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas, USA

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Naifa L Busaidy Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas MD Anderson Cancer Center, Houston, Texas, USA

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Steven I Sherman Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas MD Anderson Cancer Center, Houston, Texas, USA

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Stephen Y Lai Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas, USA

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Mark Zafereo Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas, USA

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Maria E Cabanillas Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas MD Anderson Cancer Center, Houston, Texas, USA

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Theodon H Bessiene L Bricaire L Bonnet-Serrano F Cochand-Priollet B Leroy K Garinet S Pasmant E Zerbit J 2022 Redifferentiating effect of larotrectinib in NTRK-rearranged advanced radioactive-iodine refractory thyroid cancer . Thyroid 32

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Anna Angelousi 1st Department of Internal Medicine, Unit of Endocrinology, Laikon Hospital, Athens, Greece

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Ploutarchos Tzoulis Department of Metabolism & Experimental Therapeutics, Division of Medicine, University College London, London, UK

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Marina Tsoli 1st Department of Propaedeutic and Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece

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Eleftherios Chatzellis 251 HAF and VA Hospital, Athens, Greece

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Anna Koumarianou Fourth Department of Internal Medicine, Hematology Oncology Unit, Attikon University Hospital, National and Kapodistrian University of Athens, Greece

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Gregory Kaltsas 1st Department of Propaedeutic and Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece

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II trial of nivolumab plus ipilimumab in radioactive iodine-refractory thyroid cancer with exploratory cohorts in ATC and MTC Nivolumab plus ipilimumab, phase II (active, not recruiting) Metastatic thyroid cancer, including radioactive iodine

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Fernanda Vaisman
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Denise P Carvalho Endocrinology Service, Laboratório de Fosiologia Endócrina Doris Rosental, Endocrinology Service, National Cancer Institute, Brazil Praça da Cruz Vermelha, 23, 8° Floor, Centro, Rio de Janeiro, Rio de Janeiro, 20230-130, Brazil

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Mario Vaisman Endocrinology Service, Laboratório de Fosiologia Endócrina Doris Rosental, Endocrinology Service, National Cancer Institute, Brazil Praça da Cruz Vermelha, 23, 8° Floor, Centro, Rio de Janeiro, Rio de Janeiro, 20230-130, Brazil

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2009 Mutational profile of advanced primary and metastatic radioactive iodine-refractory thyroid cancers reveals distinct pathogenetic roles for BRAF, PIK3CA, and AKT1 . Cancer Research 69 4885 – 4893 . ( doi:10.1158/0008-5472.CAN-09

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