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Fabián Pitoia Division of Endocrinology, Hospital de Clínicas, University of Buenos Aires

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Fernando Jerkovich Division of Endocrinology, Hospital de Clínicas, University of Buenos Aires

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Anabella Smulever Division of Endocrinology, Hospital de Clínicas, University of Buenos Aires

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Gabriela Brenta Division of Endocrinology, Dr. César Milstein Hospital, Buenos Aires, Argentina

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Fernanda Bueno Division of Endocrinology, Hospital de Clínicas, University of Buenos Aires

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Graciela Cross Division of Endocrinology, Hospital de Clínicas, University of Buenos Aires

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to establish the probability of a structural incomplete response (SIR) [ 18 ], which made it necessary to create a risk of recurrence (RR) stratification system that was validated in several cohorts of patients around the world [ 18 , 19 , 20 , 21

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Marie Alix Balay Hôpital Saint Louis, Assistance Publique – Hôpitaux de Paris (AP-HP), Paris, France

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Patrick Aidan American Hospital of Paris, Neuilly sur Seine, France

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Marie Helene Schlageter Hôpital Saint Louis, Assistance Publique – Hôpitaux de Paris (AP-HP), Paris, France

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Odette Georges American Hospital of Paris, Neuilly sur Seine, France

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Taly Meas Hôpital Saint Louis, Assistance Publique – Hôpitaux de Paris (AP-HP), Paris, France

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Maroun Bechara American Hospital of Paris, Neuilly sur Seine, France

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Marie Elisabeth Toubert Hôpital Saint Louis, Assistance Publique – Hôpitaux de Paris (AP-HP), Paris, France

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Isabelle Faugeron Hôpital Saint Louis, Assistance Publique – Hôpitaux de Paris (AP-HP), Paris, France

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Herve Monpeyssen American Hospital of Paris, Neuilly sur Seine, France

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Cécile N. Chougnet Hôpital Saint Louis, Assistance Publique – Hôpitaux de Paris (AP-HP), Paris, France

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. Structural incomplete response: structural or functional evidence of disease with any Tg level, with or without anti-Tg Ab. Indeterminate response: nonspecific biochemical or structural findings that cannot be confidently classified as either benign or

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Carla Gambale Department of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, Pisa, Italy

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Alessandro Prete Department of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, Pisa, Italy

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Lea Contartese Department of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, Pisa, Italy

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Liborio Torregrossa Department of Surgical, Medical, Molecular Pathology and Critical Area, Anatomic Pathology Section, University Hospital of Pisa, Pisa, Italy

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Francesca Bianchi Department of Nuclear Medicine, University Hospital of Pisa, Pisa, Italy

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Eleonora Molinaro Department of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, Pisa, Italy

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Gabriele Materazzi Department of Surgical, Medical, Molecular Pathology and Critical Area, Unit of Endocrine Surgery, University Hospital of Pisa, Pisa, Italy

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Rossella Elisei Department of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, Pisa, Italy

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Antonio Matrone Department of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, Pisa, Italy

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Background

Second 131I treatment is commonly performed in clinical practice in patients with differentiated thyroid cancer and biochemical incomplete or indeterminate response (BiR/InR) after initial treatment.

Objective

The objective of the is study is to evaluate the clinical impact of the second 131I treatment in BiR/InR patients and analyze the predictive factors for structural incomplete response (SiR).

Patients and methods

One hundred fifty-three BiR/InR patients after initial treatment who received a second 131I treatment were included in the study. The clinical response in a short- and medium- long-term follow-up was evaluated.

Results

After the second 131I treatment (median 8 months), 11.8% patients showed excellent response (ER), 17% SiR, while BiR/InR persisted in 71.2%. Less than half (38.5%) of SiR patients had radioiodine-avid metastases. Patients who, following the second 131I treatment, experienced SiR had larger tumor size and more frequently aggressive histology and vascular invasion than those experienced BiR/InR and ER. Also, the median values of thyroglobulin on levothyroxine therapy (LT4-Tg), Tg peak after recombinant human TSH stimulation (rhTSH-Tg) and thyroglobulin antibodies (TgAb) were significantly higher in patients who developed SiR. At last evaluation (median: 9.9 years), BiR/InR persisted in 57.5%, while 26.2% and 16.3% of the patients showed ER and SiR, respectively. About half of BiR/InR patients (71/153 (46.4%)) received further treatments after the second 131I treatment.

Conclusions

Radioiodine-avid metastatic disease detected by the second 131I is an infrequent finding in patients with BiR/InR after initial treatment. However, specific pathologic and biochemical features allow to better identify those cases with higher probability of developing SiR, thus improving the clinical effectiveness of performing a second 131I treatment.

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Amanda La Greca Endocrinology Service, Department of Medicine, New York, N.Y., USA

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Bin Xu Department of Pathology, Memorial Sloan-Kettering Cancer Center and Weill-Cornell College of Medicine, New York, N.Y., USA

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Ronald Ghossein Department of Pathology, Memorial Sloan-Kettering Cancer Center and Weill-Cornell College of Medicine, New York, N.Y., USA

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R. Michael Tuttle Endocrinology Service, Department of Medicine, New York, N.Y., USA

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Mona M. Sabra Endocrinology Service, Department of Medicine, New York, N.Y., USA

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findings, or (4) a structural incomplete response if they had structural evidence of disease regardless of Tg or TgAb levels. Patients who received a total thyroidectomy without RAI ablation were classified as having: (1) an excellent response if they

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Germán A. Jimenez Londoño Nuclear Medicine Department, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain

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Ana Maria Garcia Vicente Nuclear Medicine Department, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain

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Julia Sastre Marcos Department of Endocrinology, Complejo Hospitalario de Toledo, Toledo, Spain

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Francisco Jose Pena Pardo Nuclear Medicine Department, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain

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Mariano Amo-Salas Department of Mathematics, University of Castilla-La Mancha, Ciudad Real, Spain

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Manuel Moreno Caballero Department of Nuclear Medicine, Hospital Universitario Infanta Cristina Badajoz, Badajoz, Spain

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Maria Prado Talavera Rubio  Nuclear Medicine Department, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain

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Beatriz Gonzalez Garcia Nuclear Medicine Department, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain

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Niletys Dafne Disotuar Ruiz Nuclear Medicine Department, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain

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Angel Maria Soriano Castrejón Nuclear Medicine Department, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain

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patient based on the response to initial therapy (excellent, indeterminate, biochemical incomplete and structural incomplete response) using Preablation thyroglobulin (pTg), preablation AntiTg antibodies (pAntiTgAb), ultrasonography (US), diagnostic whole

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Marco Capezzone Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy

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Noemi Fralassi Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy

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Chiara Secchi Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy

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Silvia Cantara Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy

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Lucia Brilli Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy

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Tania Pilli Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy

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Fabio Maino Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy

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Raffaella Forleo Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy

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Furio Pacini Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy

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Gabriele Cevenini Department of Medical Biotechnologies, University of Siena, Siena, Italy

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Alessandra Cartocci Department of Medical Biotechnologies, University of Siena, Siena, Italy

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Maria Grazia Castagna Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy

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disease; a structural incomplete response if there were persistent or newly identified loco-regional or distant metastases and, finally, an indeterminate response if there were non-specific biochemical or structural findings that could not be confidently

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Noha Mukhtar Department of Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia

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Hadeel Aljamei Department of Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia

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Abeer Aljomaiah Department of Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia

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Yosra Moria Department of Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia

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Ali S. Alzahrani Department of Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia

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initial management, 5 (4.4%) patients were in an excellent response, 24 (21.1%) in an indeterminate response, 15 (13.2%) in a biochemically incomplete response, and 70 (61.4%) in a structurally incomplete response (online suppl. Table 3). The response to

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Markus Eszlinger Departments of Oncology, Pathology and Laboratory Medicine, Biochemistry and Molecular Biology, and Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Heritage Medical Research Building, Calgary, Alberta, Canada
Institute of Pathology, University Hospital Halle (Saale), Halle (Saale), Germany

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Paul Stewardson Department of Medical Science and Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, Canada

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John B McIntyre Precision Oncology Hub Laboratory, Alberta Health Services, Tom Baker Cancer Centre, Calgary, Alberta, Canada

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Adrian Box Department of Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary, Calgary, Canada

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Moosa Khalil Department of Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary, Calgary, Canada

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Martin Hyrcza Department of Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary, Calgary, Canada

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Konstantin Koro Department of Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary, Calgary, Canada

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Dean Ruether Section of Medical Oncology, Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, Canada

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Jiahui Wu Department of Medical Science and Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, Canada

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Ralf Paschke Departments of Medicine, Oncology, Pathology and Laboratory Medicine, Biochemistry and Molecular Biology, and Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Heritage Medical Research Building, Calgary, Alberta, Canada

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the percentages of indeterminate response, structural incomplete response, and biochemical incomplete response, or the mean and median follow-up time. Analysis B included 44 patients distinct from those included in Analysis A; 42 of these patients

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Renata Alencar Endocrinology Service, Department of Medicine, Instituto Nacional do Cancer (INCA), Rio de Janeiro, Brazil
Endocrinology Service, Department of Medicine, Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, Brazil

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Daniel Barretto Kendler Endocrinology Service, Department of Medicine, Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, Brazil

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Fernanda Andrade Endocrinology Service, Department of Medicine, Instituto Nacional do Cancer (INCA), Rio de Janeiro, Brazil

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Carla Nava Endocrinology Service, Department of Medicine, Instituto Nacional do Cancer (INCA), Rio de Janeiro, Brazil

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Daniel Bulzico Endocrinology Service, Department of Medicine, Instituto Nacional do Cancer (INCA), Rio de Janeiro, Brazil

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Cencita Cordeiro de Noronha Pessoa Endocrinology Service, Department of Medicine, Instituto Nacional do Cancer (INCA), Rio de Janeiro, Brazil

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Rossana Corbo Endocrinology Service, Department of Medicine, Instituto Nacional do Cancer (INCA), Rio de Janeiro, Brazil
Endocrinology Service, Department of Medicine, Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, Brazil

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Fernanda Vaisman Endocrinology Service, Department of Medicine, Instituto Nacional do Cancer (INCA), Rio de Janeiro, Brazil
Endocrinology Service, Department of Medicine, Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, Brazil

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(c) structural incomplete response – persistent/recurrent structural disease regardless of calcitonin and CEA. To determine the final status, at the end of the follow-up period the patients were categorized as (a) free of disease – undetectable

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Rony Ruben Department of Endocrinology, Amrita Institute of Medical Sciences, Kochi, India

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Praveen V. Pavithran Department of Endocrinology, Amrita Institute of Medical Sciences, Kochi, India

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V. Usha Menon Department of Endocrinology, Amrita Institute of Medical Sciences, Kochi, India

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Vasantha Nair Department of Endocrinology, Amrita Institute of Medical Sciences, Kochi, India

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Harish Kumar Department of Endocrinology, Amrita Institute of Medical Sciences, Kochi, India

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response initially did so. On follow-up, 40.1% of the patients, who were in the indeterminate category initially also had NED. Among the patients with structural incomplete response, 57.1% remained as PSD. Only 9.1% of patients, who had biochemical

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