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Quantitative imaging biomarkers of immune-related adverse events in immune-checkpoint blockade-treated metastatic melanoma patients: a pilot study

PURPOSE: To develop quantitative molecular imaging biomarkers of immune-related adverse event (irAE) development in malignant melanoma (MM) patients receiving immune-checkpoint inhibitors (ICI) imaged with (18)F-FDG PET/CT. METHODS: (18)F-FDG PET/CT images of 58 MM patients treated with anti-PD-1 or...

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Autores principales: Hribernik, Nežka, Huff, Daniel T, Studen, Andrej, Zevnik, Katarina, Klaneček, Žan, Emamekhoo, Hamid, Škalic, Katja, Jeraj, Robert, Reberšek, Martina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9016045/
https://www.ncbi.nlm.nih.gov/pubmed/34958422
http://dx.doi.org/10.1007/s00259-021-05650-3
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author Hribernik, Nežka
Huff, Daniel T
Studen, Andrej
Zevnik, Katarina
Klaneček, Žan
Emamekhoo, Hamid
Škalic, Katja
Jeraj, Robert
Reberšek, Martina
author_facet Hribernik, Nežka
Huff, Daniel T
Studen, Andrej
Zevnik, Katarina
Klaneček, Žan
Emamekhoo, Hamid
Škalic, Katja
Jeraj, Robert
Reberšek, Martina
author_sort Hribernik, Nežka
collection PubMed
description PURPOSE: To develop quantitative molecular imaging biomarkers of immune-related adverse event (irAE) development in malignant melanoma (MM) patients receiving immune-checkpoint inhibitors (ICI) imaged with (18)F-FDG PET/CT. METHODS: (18)F-FDG PET/CT images of 58 MM patients treated with anti-PD-1 or anti-CTLA-4 ICI were retrospectively analyzed for indication of irAE. Three target organs, most commonly affected by irAE, were considered: bowel, lung, and thyroid. Patient charts were reviewed to identify which patients experienced irAE, irAE grade, and time to irAE diagnosis. Target organs were segmented using a convolutional neural network (CNN), and novel quantitative imaging biomarkers — SUV percentiles (SUV(X%)) of (18)F-FDG uptake within the target organs — were correlated with the clinical irAE status. Area under the receiver-operating characteristic curve (AUROC) was used to quantify irAE detection performance. Patients who did not experience irAE were used to establish normal ranges for target organ (18)F-FDG uptake. RESULTS: A total of 31% (18/58) patients experienced irAE in the three target organs: bowel (n=6), lung (n=5), and thyroid (n=9). Optimal percentiles for identifying irAE were bowel (SUV(95%), AUROC=0.79), lung (SUV(95%), AUROC=0.98), and thyroid (SUV(75%), AUROC=0.88). Optimal cut-offs for irAE detection were bowel (SUV(95%)>2.7 g/mL), lung (SUV(95%)>1.7 g/mL), and thyroid (SUV(75%)>2.1 g/mL). Normal ranges (95% confidence interval) for the SUV percentiles in patients without irAE were bowel [1.74, 2.86 g/mL], lung [0.73, 1.46 g/mL], and thyroid [0.86, 1.99 g/mL]. CONCLUSIONS: Increased (18)F-FDG uptake within irAE-affected organs provides predictive information about the development of irAE in MM patients receiving ICI and represents a potential quantitative imaging biomarker for irAE. Some irAE can be detected on (18)F-FDG PET/CT well before clinical symptoms appear.
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spelling pubmed-90160452022-05-02 Quantitative imaging biomarkers of immune-related adverse events in immune-checkpoint blockade-treated metastatic melanoma patients: a pilot study Hribernik, Nežka Huff, Daniel T Studen, Andrej Zevnik, Katarina Klaneček, Žan Emamekhoo, Hamid Škalic, Katja Jeraj, Robert Reberšek, Martina Eur J Nucl Med Mol Imaging Original Article PURPOSE: To develop quantitative molecular imaging biomarkers of immune-related adverse event (irAE) development in malignant melanoma (MM) patients receiving immune-checkpoint inhibitors (ICI) imaged with (18)F-FDG PET/CT. METHODS: (18)F-FDG PET/CT images of 58 MM patients treated with anti-PD-1 or anti-CTLA-4 ICI were retrospectively analyzed for indication of irAE. Three target organs, most commonly affected by irAE, were considered: bowel, lung, and thyroid. Patient charts were reviewed to identify which patients experienced irAE, irAE grade, and time to irAE diagnosis. Target organs were segmented using a convolutional neural network (CNN), and novel quantitative imaging biomarkers — SUV percentiles (SUV(X%)) of (18)F-FDG uptake within the target organs — were correlated with the clinical irAE status. Area under the receiver-operating characteristic curve (AUROC) was used to quantify irAE detection performance. Patients who did not experience irAE were used to establish normal ranges for target organ (18)F-FDG uptake. RESULTS: A total of 31% (18/58) patients experienced irAE in the three target organs: bowel (n=6), lung (n=5), and thyroid (n=9). Optimal percentiles for identifying irAE were bowel (SUV(95%), AUROC=0.79), lung (SUV(95%), AUROC=0.98), and thyroid (SUV(75%), AUROC=0.88). Optimal cut-offs for irAE detection were bowel (SUV(95%)>2.7 g/mL), lung (SUV(95%)>1.7 g/mL), and thyroid (SUV(75%)>2.1 g/mL). Normal ranges (95% confidence interval) for the SUV percentiles in patients without irAE were bowel [1.74, 2.86 g/mL], lung [0.73, 1.46 g/mL], and thyroid [0.86, 1.99 g/mL]. CONCLUSIONS: Increased (18)F-FDG uptake within irAE-affected organs provides predictive information about the development of irAE in MM patients receiving ICI and represents a potential quantitative imaging biomarker for irAE. Some irAE can be detected on (18)F-FDG PET/CT well before clinical symptoms appear. Springer Berlin Heidelberg 2021-12-27 2022 /pmc/articles/PMC9016045/ /pubmed/34958422 http://dx.doi.org/10.1007/s00259-021-05650-3 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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
Hribernik, Nežka
Huff, Daniel T
Studen, Andrej
Zevnik, Katarina
Klaneček, Žan
Emamekhoo, Hamid
Škalic, Katja
Jeraj, Robert
Reberšek, Martina
Quantitative imaging biomarkers of immune-related adverse events in immune-checkpoint blockade-treated metastatic melanoma patients: a pilot study
title Quantitative imaging biomarkers of immune-related adverse events in immune-checkpoint blockade-treated metastatic melanoma patients: a pilot study
title_full Quantitative imaging biomarkers of immune-related adverse events in immune-checkpoint blockade-treated metastatic melanoma patients: a pilot study
title_fullStr Quantitative imaging biomarkers of immune-related adverse events in immune-checkpoint blockade-treated metastatic melanoma patients: a pilot study
title_full_unstemmed Quantitative imaging biomarkers of immune-related adverse events in immune-checkpoint blockade-treated metastatic melanoma patients: a pilot study
title_short Quantitative imaging biomarkers of immune-related adverse events in immune-checkpoint blockade-treated metastatic melanoma patients: a pilot study
title_sort quantitative imaging biomarkers of immune-related adverse events in immune-checkpoint blockade-treated metastatic melanoma patients: a pilot study
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9016045/
https://www.ncbi.nlm.nih.gov/pubmed/34958422
http://dx.doi.org/10.1007/s00259-021-05650-3
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