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RADTHYR: an open-label, single-arm, prospective multicenter phase II trial of Radium-223 for the treatment of bone metastases from radioactive iodine refractory differentiated thyroid cancer

PURPOSE: This is the first prospective trial evaluating the efficacy of alpha emitter Radium-223 in patients with bone metastases from radioactive iodine (RAI) refractory (RAIR) differentiated thyroid cancer. METHODS: RADTHYR is a multicenter, single-arm prospective Simon two-stage phase II trial (N...

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Autores principales: Deandreis, Désirée, Maillard, Aline, Zerdoud, Slimane, Bournaud, Claire, Vija, Lavinia, Sajous, Christophe, Terroir, Marie, Leenhardt, Laurence, Schlumberger, Martin, Borget, Isabelle, Leboulleux, Sophie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426251/
https://www.ncbi.nlm.nih.gov/pubmed/33619600
http://dx.doi.org/10.1007/s00259-021-05229-y
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author Deandreis, Désirée
Maillard, Aline
Zerdoud, Slimane
Bournaud, Claire
Vija, Lavinia
Sajous, Christophe
Terroir, Marie
Leenhardt, Laurence
Schlumberger, Martin
Borget, Isabelle
Leboulleux, Sophie
author_facet Deandreis, Désirée
Maillard, Aline
Zerdoud, Slimane
Bournaud, Claire
Vija, Lavinia
Sajous, Christophe
Terroir, Marie
Leenhardt, Laurence
Schlumberger, Martin
Borget, Isabelle
Leboulleux, Sophie
author_sort Deandreis, Désirée
collection PubMed
description PURPOSE: This is the first prospective trial evaluating the efficacy of alpha emitter Radium-223 in patients with bone metastases from radioactive iodine (RAI) refractory (RAIR) differentiated thyroid cancer. METHODS: RADTHYR is a multicenter, single-arm prospective Simon two-stage phase II trial (NCT02390934). The primary objective was to establish the efficacy of three administrations of 55 kBq/kg of Radium-223 by (18)F-FDG PET/CT according to PERCIST criteria. Secondary objectives were to establish the efficacy of six administrations of Radium-223 by (18)F-FDG PET/CT, (99m)Tc-HMDP bone scan and (18)FNa PET/CT, clinical benefits, changes in serum bone markers, thyroglobulin levels, and safety. RESULTS: Ten patients were enrolled between July 2015 and December 2017 (4 M; median age 74 years). Prior to Radium-223 administration, patients received a median RAI cumulative activity of 15 GBq (7.4–35.6), external radiation therapy (n = 9), bone surgery (n = 8), cimentoplasty (n = 5), and cryoablation (n = 2). (18)F-FDG PET/CT showed stable disease (SD) in 4/10 and progressive disease (PD) in 6/10 cases after three administrations and SD in 4/10, PD in 5/10 cases, and 1/10 non-evaluable (NE) case after six administrations. After six injections, (99m)Tc-HMDP bone scan showed SD in 9 cases and was NE in 1 case; (18)FNa PET/CT showed SD in 8 cases, partial response (PR) in 1 case, and was NE in 1 case. No significant clinical benefits were reported during the study. A skeletal event occurred in 6 patients (median time without skeletal event of 12.1 months). Seventy-seven adverse events were reported during treatment (7 of grade 3–4). Three patients developed an acute myeloid, a promyelocytic, and a chronic myeloid leukemia after the last Radium-223 administration considered as drug-related. CONCLUSION: The trial was stopped after interim analysis for lack of response of bone metastases from RAIR thyroid cancer to Radium-223. Severe hematological toxicity was observed in patients heavily pretreated with RAI and external radiation. TRIAL REGISTRATION NUMBER: NCT02390934. Registration date 18.03.2015. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00259-021-05229-y.
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spelling pubmed-84262512021-09-09 RADTHYR: an open-label, single-arm, prospective multicenter phase II trial of Radium-223 for the treatment of bone metastases from radioactive iodine refractory differentiated thyroid cancer Deandreis, Désirée Maillard, Aline Zerdoud, Slimane Bournaud, Claire Vija, Lavinia Sajous, Christophe Terroir, Marie Leenhardt, Laurence Schlumberger, Martin Borget, Isabelle Leboulleux, Sophie Eur J Nucl Med Mol Imaging Original Article PURPOSE: This is the first prospective trial evaluating the efficacy of alpha emitter Radium-223 in patients with bone metastases from radioactive iodine (RAI) refractory (RAIR) differentiated thyroid cancer. METHODS: RADTHYR is a multicenter, single-arm prospective Simon two-stage phase II trial (NCT02390934). The primary objective was to establish the efficacy of three administrations of 55 kBq/kg of Radium-223 by (18)F-FDG PET/CT according to PERCIST criteria. Secondary objectives were to establish the efficacy of six administrations of Radium-223 by (18)F-FDG PET/CT, (99m)Tc-HMDP bone scan and (18)FNa PET/CT, clinical benefits, changes in serum bone markers, thyroglobulin levels, and safety. RESULTS: Ten patients were enrolled between July 2015 and December 2017 (4 M; median age 74 years). Prior to Radium-223 administration, patients received a median RAI cumulative activity of 15 GBq (7.4–35.6), external radiation therapy (n = 9), bone surgery (n = 8), cimentoplasty (n = 5), and cryoablation (n = 2). (18)F-FDG PET/CT showed stable disease (SD) in 4/10 and progressive disease (PD) in 6/10 cases after three administrations and SD in 4/10, PD in 5/10 cases, and 1/10 non-evaluable (NE) case after six administrations. After six injections, (99m)Tc-HMDP bone scan showed SD in 9 cases and was NE in 1 case; (18)FNa PET/CT showed SD in 8 cases, partial response (PR) in 1 case, and was NE in 1 case. No significant clinical benefits were reported during the study. A skeletal event occurred in 6 patients (median time without skeletal event of 12.1 months). Seventy-seven adverse events were reported during treatment (7 of grade 3–4). Three patients developed an acute myeloid, a promyelocytic, and a chronic myeloid leukemia after the last Radium-223 administration considered as drug-related. CONCLUSION: The trial was stopped after interim analysis for lack of response of bone metastases from RAIR thyroid cancer to Radium-223. Severe hematological toxicity was observed in patients heavily pretreated with RAI and external radiation. TRIAL REGISTRATION NUMBER: NCT02390934. Registration date 18.03.2015. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00259-021-05229-y. Springer Berlin Heidelberg 2021-02-23 2021 /pmc/articles/PMC8426251/ /pubmed/33619600 http://dx.doi.org/10.1007/s00259-021-05229-y Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
Deandreis, Désirée
Maillard, Aline
Zerdoud, Slimane
Bournaud, Claire
Vija, Lavinia
Sajous, Christophe
Terroir, Marie
Leenhardt, Laurence
Schlumberger, Martin
Borget, Isabelle
Leboulleux, Sophie
RADTHYR: an open-label, single-arm, prospective multicenter phase II trial of Radium-223 for the treatment of bone metastases from radioactive iodine refractory differentiated thyroid cancer
title RADTHYR: an open-label, single-arm, prospective multicenter phase II trial of Radium-223 for the treatment of bone metastases from radioactive iodine refractory differentiated thyroid cancer
title_full RADTHYR: an open-label, single-arm, prospective multicenter phase II trial of Radium-223 for the treatment of bone metastases from radioactive iodine refractory differentiated thyroid cancer
title_fullStr RADTHYR: an open-label, single-arm, prospective multicenter phase II trial of Radium-223 for the treatment of bone metastases from radioactive iodine refractory differentiated thyroid cancer
title_full_unstemmed RADTHYR: an open-label, single-arm, prospective multicenter phase II trial of Radium-223 for the treatment of bone metastases from radioactive iodine refractory differentiated thyroid cancer
title_short RADTHYR: an open-label, single-arm, prospective multicenter phase II trial of Radium-223 for the treatment of bone metastases from radioactive iodine refractory differentiated thyroid cancer
title_sort radthyr: an open-label, single-arm, prospective multicenter phase ii trial of radium-223 for the treatment of bone metastases from radioactive iodine refractory differentiated thyroid cancer
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426251/
https://www.ncbi.nlm.nih.gov/pubmed/33619600
http://dx.doi.org/10.1007/s00259-021-05229-y
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