Liquid profiling of circulating tumor DNA in colorectal cancer: steps needed to achieve its full clinical value as standard care

The analysis of circulating tumor DNA (ctDNA) is at the threshold of implementation into standard care for colorectal cancer (CRC) patients. However, data about the clinical utility of liquid profiling (LP), its acceptance by clinicians, and its integration into clinical workflows in real‐world sett...

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Main Authors: Maren Hedtke, Rodrigo Pessoa Rejas, Matthias F. Froelich, Volker Ast, Angelika Duda, Laura Mirbach, Victor Costina, Uwe M. Martens, Ralf‐Dieter Hofheinz, Michael Neumaier, Verena Haselmann
Format: Article
Language:English
Published: Wiley 2022-05-01
Series:Molecular Oncology
Subjects:
Online Access:https://doi.org/10.1002/1878-0261.13156
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author Maren Hedtke
Rodrigo Pessoa Rejas
Matthias F. Froelich
Volker Ast
Angelika Duda
Laura Mirbach
Victor Costina
Uwe M. Martens
Ralf‐Dieter Hofheinz
Michael Neumaier
Verena Haselmann
author_facet Maren Hedtke
Rodrigo Pessoa Rejas
Matthias F. Froelich
Volker Ast
Angelika Duda
Laura Mirbach
Victor Costina
Uwe M. Martens
Ralf‐Dieter Hofheinz
Michael Neumaier
Verena Haselmann
author_sort Maren Hedtke
collection DOAJ
description The analysis of circulating tumor DNA (ctDNA) is at the threshold of implementation into standard care for colorectal cancer (CRC) patients. However, data about the clinical utility of liquid profiling (LP), its acceptance by clinicians, and its integration into clinical workflows in real‐world settings remain limited. Here, LP tests requested as part of routine care since 2016 were retrospectively evaluated. Results show restrained request behavior that improved moderately over time, as well as reliable diagnostic performance comparable to translational studies, with an overall agreement of 91.7%. Extremely low ctDNA levels at < 0.1% in over 20% of cases, a high frequency of concomitant driver mutations (in up to 14% of cases), and ctDNA levels reflecting the clinical course of disease were revealed. However, certain limitations hampering successful translation of ctDNA into clinical practice were uncovered, including the lack of clinically relevant ctDNA thresholds, appropriate time points of LP requests, and integrative evaluation of ctDNA, imaging, and clinical findings. In conclusion, these results highlight the potential clinical value of LP for CRC patient management and demonstrate issues that need to be addressed for successful long‐term implementation in clinical workflows.
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spelling doaj.art-c1e5149860064c5e8fd192d932a6be652022-12-22T03:25:43ZengWileyMolecular Oncology1574-78911878-02612022-05-0116102042205610.1002/1878-0261.13156Liquid profiling of circulating tumor DNA in colorectal cancer: steps needed to achieve its full clinical value as standard careMaren Hedtke0Rodrigo Pessoa Rejas1Matthias F. Froelich2Volker Ast3Angelika Duda4Laura Mirbach5Victor Costina6Uwe M. Martens7Ralf‐Dieter Hofheinz8Michael Neumaier9Verena Haselmann10Institute of Clinical Chemistry Medical Faculty Mannheim of the University of Heidelberg University Hospital Mannheim GermanyInstitute of Clinical Chemistry Medical Faculty Mannheim of the University of Heidelberg University Hospital Mannheim GermanyDepartment of Radiology and Nuclear Medicine University Medicine Mannheim Medical Faculty Mannheim of the University of Heidelberg GermanyInstitute of Clinical Chemistry Medical Faculty Mannheim of the University of Heidelberg University Hospital Mannheim GermanyInstitute of Clinical Chemistry Medical Faculty Mannheim of the University of Heidelberg University Hospital Mannheim GermanyInstitute of Clinical Chemistry Medical Faculty Mannheim of the University of Heidelberg University Hospital Mannheim GermanyInstitute of Clinical Chemistry Medical Faculty Mannheim of the University of Heidelberg University Hospital Mannheim GermanyCancer Center Heilbronn‐Franken SLK‐Clinics MOLIT Institute for Personalized Medicine Heilbronn GermanyDay Treatment Center (TTZ) Interdisciplinary Tumor Center Mannheim (ITM) III Medical Clinic Medical Faculty Mannheim of the University of Heidelberg University Hospital Mannheim GermanyInstitute of Clinical Chemistry Medical Faculty Mannheim of the University of Heidelberg University Hospital Mannheim GermanyInstitute of Clinical Chemistry Medical Faculty Mannheim of the University of Heidelberg University Hospital Mannheim GermanyThe analysis of circulating tumor DNA (ctDNA) is at the threshold of implementation into standard care for colorectal cancer (CRC) patients. However, data about the clinical utility of liquid profiling (LP), its acceptance by clinicians, and its integration into clinical workflows in real‐world settings remain limited. Here, LP tests requested as part of routine care since 2016 were retrospectively evaluated. Results show restrained request behavior that improved moderately over time, as well as reliable diagnostic performance comparable to translational studies, with an overall agreement of 91.7%. Extremely low ctDNA levels at < 0.1% in over 20% of cases, a high frequency of concomitant driver mutations (in up to 14% of cases), and ctDNA levels reflecting the clinical course of disease were revealed. However, certain limitations hampering successful translation of ctDNA into clinical practice were uncovered, including the lack of clinically relevant ctDNA thresholds, appropriate time points of LP requests, and integrative evaluation of ctDNA, imaging, and clinical findings. In conclusion, these results highlight the potential clinical value of LP for CRC patient management and demonstrate issues that need to be addressed for successful long‐term implementation in clinical workflows.https://doi.org/10.1002/1878-0261.13156colorectal cancerctDNAliquid biopsyliquid profilingreal‐world
spellingShingle Maren Hedtke
Rodrigo Pessoa Rejas
Matthias F. Froelich
Volker Ast
Angelika Duda
Laura Mirbach
Victor Costina
Uwe M. Martens
Ralf‐Dieter Hofheinz
Michael Neumaier
Verena Haselmann
Liquid profiling of circulating tumor DNA in colorectal cancer: steps needed to achieve its full clinical value as standard care
Molecular Oncology
colorectal cancer
ctDNA
liquid biopsy
liquid profiling
real‐world
title Liquid profiling of circulating tumor DNA in colorectal cancer: steps needed to achieve its full clinical value as standard care
title_full Liquid profiling of circulating tumor DNA in colorectal cancer: steps needed to achieve its full clinical value as standard care
title_fullStr Liquid profiling of circulating tumor DNA in colorectal cancer: steps needed to achieve its full clinical value as standard care
title_full_unstemmed Liquid profiling of circulating tumor DNA in colorectal cancer: steps needed to achieve its full clinical value as standard care
title_short Liquid profiling of circulating tumor DNA in colorectal cancer: steps needed to achieve its full clinical value as standard care
title_sort liquid profiling of circulating tumor dna in colorectal cancer steps needed to achieve its full clinical value as standard care
topic colorectal cancer
ctDNA
liquid biopsy
liquid profiling
real‐world
url https://doi.org/10.1002/1878-0261.13156
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