Current and Future Clinical Applications of ctDNA in Immuno-Oncology

Testing peripheral blood for circulating tumor DNA (ctDNA) offers a minimally invasive opportunity to diagnose, characterize, and monitor the disease in individual cancer patients. ctDNA can reflect the actual tumor burden and specific genomic state of disease and thus might serve as a prognostic an...

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Published inCancer research (Chicago, Ill.) Vol. 82; no. 3; pp. 349 - 358
Main Authors Stadler, Julia-Christina, Belloum, Yassine, Deitert, Benjamin, Sementsov, Mark, Heidrich, Isabel, Gebhardt, Christoffer, Keller, Laura, Pantel, Klaus
Format Journal Article
LanguageEnglish
Published United States American Association for Cancer Research 01.02.2022
Subjects
Biomarkers, Tumor - genetics
Circulating Tumor DNA - metabolism
Humans
Immunotherapy - methods
Life Sciences
Review
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Abstract Testing peripheral blood for circulating tumor DNA (ctDNA) offers a minimally invasive opportunity to diagnose, characterize, and monitor the disease in individual cancer patients. ctDNA can reflect the actual tumor burden and specific genomic state of disease and thus might serve as a prognostic and predictive biomarker for immune checkpoint inhibitor (ICI) therapy. Recent studies in various cancer entities (e.g., melanoma, non–small cell lung cancer, colon cancer, and urothelial cancer) have shown that sequential ctDNA analyses allow for the identification of responders to ICI therapy, with a significant lead time to imaging. ctDNA assessment may also help distinguish pseudoprogression under ICI therapy from real progression. Developing dynamic changes in ctDNA concentrations as a potential surrogate endpoint of clinical efficacy in patients undergoing adjuvant immunotherapy is ongoing. Besides overall ctDNA burden, further ctDNA characterization can help uncover tumor-specific determinants (e.g., tumor mutational burden and microsatellite instability) of responses or resistance to immunotherapy. In future studies, standardized ctDNA assessments need to be included in interventional clinical trials across cancer entities to demonstrate the clinical utility of ctDNA as a biomarker for personalized cancer immunotherapy.
AbstractList Testing peripheral blood for circulating tumor DNA (ctDNA) offers a minimally invasive opportunity to diagnose, characterize, and monitor the disease in individual cancer patients. ctDNA can reflect the actual tumor burden and specific genomic state of disease and thus might serve as a prognostic and predictive biomarker for immune checkpoint inhibitor (ICI) therapy. Recent studies in various cancer entities (e.g., melanoma, non-small cell lung cancer, colon cancer, and urothelial cancer) have shown that sequential ctDNA analyses allow for the identification of responders to ICI therapy, with a significant lead time to imaging. ctDNA assessment may also help distinguish pseudoprogression under ICI therapy from real progression. Developing dynamic changes in ctDNA concentrations as a potential surrogate endpoint of clinical efficacy in patients undergoing adjuvant immunotherapy is ongoing. Besides overall ctDNA burden, further ctDNA characterization can help uncover tumor-specific determinants (e.g., tumor mutational burden and microsatellite instability) of responses or resistance to immunotherapy. In future studies, standardized ctDNA assessments need to be included in interventional clinical trials across cancer entities to demonstrate the clinical utility of ctDNA as a biomarker for personalized cancer immunotherapy.
Testing peripheral blood for circulating tumor DNA (ctDNA) offers a minimally invasive opportunity to diagnose, characterize, and monitor the disease in individual cancer patients. ctDNA can reflect the actual tumor burden and specific genomic state of disease and thus might serve as a prognostic and predictive biomarker for immune checkpoint inhibitor (ICI) therapy. Recent studies in various cancer entities (e.g., melanoma, non-small cell lung cancer, colon cancer, and urothelial cancer) have shown that sequential ctDNA analyses allow for the identification of responders to ICI therapy, with a significant lead time to imaging. ctDNA assessment may also help distinguish pseudoprogression under ICI therapy from real progression. Developing dynamic changes in ctDNA concentrations as a potential surrogate endpoint of clinical efficacy in patients undergoing adjuvant immunotherapy is ongoing. Besides overall ctDNA burden, further ctDNA characterization can help uncover tumor-specific determinants (e.g., tumor mutational burden and microsatellite instability) of responses or resistance to immunotherapy. In future studies, standardized ctDNA assessments need to be included in interventional clinical trials across cancer entities to demonstrate the clinical utility of ctDNA as a biomarker for personalized cancer immunotherapy.Testing peripheral blood for circulating tumor DNA (ctDNA) offers a minimally invasive opportunity to diagnose, characterize, and monitor the disease in individual cancer patients. ctDNA can reflect the actual tumor burden and specific genomic state of disease and thus might serve as a prognostic and predictive biomarker for immune checkpoint inhibitor (ICI) therapy. Recent studies in various cancer entities (e.g., melanoma, non-small cell lung cancer, colon cancer, and urothelial cancer) have shown that sequential ctDNA analyses allow for the identification of responders to ICI therapy, with a significant lead time to imaging. ctDNA assessment may also help distinguish pseudoprogression under ICI therapy from real progression. Developing dynamic changes in ctDNA concentrations as a potential surrogate endpoint of clinical efficacy in patients undergoing adjuvant immunotherapy is ongoing. Besides overall ctDNA burden, further ctDNA characterization can help uncover tumor-specific determinants (e.g., tumor mutational burden and microsatellite instability) of responses or resistance to immunotherapy. In future studies, standardized ctDNA assessments need to be included in interventional clinical trials across cancer entities to demonstrate the clinical utility of ctDNA as a biomarker for personalized cancer immunotherapy.
Abstract Testing peripheral blood for circulating tumor DNA (ctDNA) offers a minimally invasive opportunity to diagnose, characterize, and monitor the disease in individual cancer patients. ctDNA can reflect the actual tumor burden and specific genomic state of disease and thus might serve as a prognostic and predictive biomarker for immune checkpoint inhibitor (ICI) therapy. Recent studies in various cancer entities (e.g., melanoma, non–small cell lung cancer, colon cancer, and urothelial cancer) have shown that sequential ctDNA analyses allow for the identification of responders to ICI therapy, with a significant lead time to imaging. ctDNA assessment may also help distinguish pseudoprogression under ICI therapy from real progression. Developing dynamic changes in ctDNA concentrations as a potential surrogate endpoint of clinical efficacy in patients undergoing adjuvant immunotherapy is ongoing. Besides overall ctDNA burden, further ctDNA characterization can help uncover tumor-specific determinants (e.g., tumor mutational burden and microsatellite instability) of responses or resistance to immunotherapy. In future studies, standardized ctDNA assessments need to be included in interventional clinical trials across cancer entities to demonstrate the clinical utility of ctDNA as a biomarker for personalized cancer immunotherapy.
Author Pantel, Klaus
Heidrich, Isabel
Keller, Laura
Gebhardt, Christoffer
Sementsov, Mark
Belloum, Yassine
Stadler, Julia-Christina
Deitert, Benjamin
AuthorAffiliation 1 Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
2 Department of Dermatology and Venereology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
3 Mildred Scheel Cancer Career Center HaTriCS4, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
AuthorAffiliation_xml – name: 2 Department of Dermatology and Venereology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
– name: 3 Mildred Scheel Cancer Career Center HaTriCS4, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
– name: 1 Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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  givenname: Julia-Christina
  surname: Stadler
  fullname: Stadler, Julia-Christina
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  surname: Belloum
  fullname: Belloum, Yassine
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L. Keller and K. Pantel contributed as co-last authors of this article.
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Snippet Testing peripheral blood for circulating tumor DNA (ctDNA) offers a minimally invasive opportunity to diagnose, characterize, and monitor the disease in...
Abstract Testing peripheral blood for circulating tumor DNA (ctDNA) offers a minimally invasive opportunity to diagnose, characterize, and monitor the disease...
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StartPage 349
SubjectTerms Biomarkers, Tumor - genetics
Circulating Tumor DNA - metabolism
Humans
Immunotherapy - methods
Life Sciences
Review
Title Current and Future Clinical Applications of ctDNA in Immuno-Oncology
URI https://www.ncbi.nlm.nih.gov/pubmed/34815256
https://www.proquest.com/docview/2601994637
https://hal.science/hal-04954580
https://pubmed.ncbi.nlm.nih.gov/PMC9397642
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