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Analysis of circulating tumor DNA during checkpoint inhibition in metastatic melanoma using a tumor-agnostic panel

Immunotherapy has revolutionized treatment of patients diagnosed with metastatic melanoma, where nearly half of patients receive clinical benefit. However, immunotherapy is also associated with immune-related adverse events, which may be severe and persistent. It is therefore important to identify p...

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Autores principales: Kisistók, Judit, Christensen, Ditte Sigaard, Rasmussen, Mads Heilskov, Duval, Lone, Aggerholm-Pedersen, Ninna, Luczak, Adam Andrzej, Sorensen, Boe Sandahl, Jakobsen, Martin Roelsgaard, Oellegaard, Trine Heide, Birkbak, Nicolai Juul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10470440/
https://www.ncbi.nlm.nih.gov/pubmed/37294123
http://dx.doi.org/10.1097/CMR.0000000000000903
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author Kisistók, Judit
Christensen, Ditte Sigaard
Rasmussen, Mads Heilskov
Duval, Lone
Aggerholm-Pedersen, Ninna
Luczak, Adam Andrzej
Sorensen, Boe Sandahl
Jakobsen, Martin Roelsgaard
Oellegaard, Trine Heide
Birkbak, Nicolai Juul
author_facet Kisistók, Judit
Christensen, Ditte Sigaard
Rasmussen, Mads Heilskov
Duval, Lone
Aggerholm-Pedersen, Ninna
Luczak, Adam Andrzej
Sorensen, Boe Sandahl
Jakobsen, Martin Roelsgaard
Oellegaard, Trine Heide
Birkbak, Nicolai Juul
author_sort Kisistók, Judit
collection PubMed
description Immunotherapy has revolutionized treatment of patients diagnosed with metastatic melanoma, where nearly half of patients receive clinical benefit. However, immunotherapy is also associated with immune-related adverse events, which may be severe and persistent. It is therefore important to identify patients that do not benefit from therapy early. Currently, regularly scheduled CT scans are used to investigate size changes in target lesions to evaluate progression and therapy response. This study aims to explore if panel-based analysis of circulating tumor DNA (ctDNA) taken at 3-week intervals may provide a window into the growing cancer, can be used to identify nonresponding patients early, and determine genomic alterations associated with acquired resistance to checkpoint immunotherapy without analysis of tumor tissue biopsies. We designed a gene panel for ctDNA analysis and sequenced 4–6 serial plasma samples from 24 patients with unresectable stage III or IV melanoma and treated with first-line checkpoint inhibitors enrolled at the Department of Oncology at Aarhus University Hospital, Denmark. TERT was the most mutated gene found in ctDNA and associated with a poor prognosis. We detected more ctDNA in patients with high metastatic load, which indicates that more aggressive tumors release more ctDNA into the bloodstream. Although we did not find evidence of specific mutations associated with acquired resistance, we did demonstrate in this limited cohort of 24 patients that untargeted, panel-based ctDNA analysis has the potential to be used as a minimally invasive tool in clinical practice to identify patients where the benefits of immunotherapy outweigh the drawbacks.
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spelling pubmed-104704402023-09-01 Analysis of circulating tumor DNA during checkpoint inhibition in metastatic melanoma using a tumor-agnostic panel Kisistók, Judit Christensen, Ditte Sigaard Rasmussen, Mads Heilskov Duval, Lone Aggerholm-Pedersen, Ninna Luczak, Adam Andrzej Sorensen, Boe Sandahl Jakobsen, Martin Roelsgaard Oellegaard, Trine Heide Birkbak, Nicolai Juul Melanoma Res Original Articles: Translational Research Immunotherapy has revolutionized treatment of patients diagnosed with metastatic melanoma, where nearly half of patients receive clinical benefit. However, immunotherapy is also associated with immune-related adverse events, which may be severe and persistent. It is therefore important to identify patients that do not benefit from therapy early. Currently, regularly scheduled CT scans are used to investigate size changes in target lesions to evaluate progression and therapy response. This study aims to explore if panel-based analysis of circulating tumor DNA (ctDNA) taken at 3-week intervals may provide a window into the growing cancer, can be used to identify nonresponding patients early, and determine genomic alterations associated with acquired resistance to checkpoint immunotherapy without analysis of tumor tissue biopsies. We designed a gene panel for ctDNA analysis and sequenced 4–6 serial plasma samples from 24 patients with unresectable stage III or IV melanoma and treated with first-line checkpoint inhibitors enrolled at the Department of Oncology at Aarhus University Hospital, Denmark. TERT was the most mutated gene found in ctDNA and associated with a poor prognosis. We detected more ctDNA in patients with high metastatic load, which indicates that more aggressive tumors release more ctDNA into the bloodstream. Although we did not find evidence of specific mutations associated with acquired resistance, we did demonstrate in this limited cohort of 24 patients that untargeted, panel-based ctDNA analysis has the potential to be used as a minimally invasive tool in clinical practice to identify patients where the benefits of immunotherapy outweigh the drawbacks. Lippincott Williams & Wilkins 2023-10 2023-06-12 /pmc/articles/PMC10470440/ /pubmed/37294123 http://dx.doi.org/10.1097/CMR.0000000000000903 Text en Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (https://creativecommons.org/licenses/by/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Original Articles: Translational Research
Kisistók, Judit
Christensen, Ditte Sigaard
Rasmussen, Mads Heilskov
Duval, Lone
Aggerholm-Pedersen, Ninna
Luczak, Adam Andrzej
Sorensen, Boe Sandahl
Jakobsen, Martin Roelsgaard
Oellegaard, Trine Heide
Birkbak, Nicolai Juul
Analysis of circulating tumor DNA during checkpoint inhibition in metastatic melanoma using a tumor-agnostic panel
title Analysis of circulating tumor DNA during checkpoint inhibition in metastatic melanoma using a tumor-agnostic panel
title_full Analysis of circulating tumor DNA during checkpoint inhibition in metastatic melanoma using a tumor-agnostic panel
title_fullStr Analysis of circulating tumor DNA during checkpoint inhibition in metastatic melanoma using a tumor-agnostic panel
title_full_unstemmed Analysis of circulating tumor DNA during checkpoint inhibition in metastatic melanoma using a tumor-agnostic panel
title_short Analysis of circulating tumor DNA during checkpoint inhibition in metastatic melanoma using a tumor-agnostic panel
title_sort analysis of circulating tumor dna during checkpoint inhibition in metastatic melanoma using a tumor-agnostic panel
topic Original Articles: Translational Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10470440/
https://www.ncbi.nlm.nih.gov/pubmed/37294123
http://dx.doi.org/10.1097/CMR.0000000000000903
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