Monitoring levels of circulating cell‐free DNA in patients with metastatic colorectal cancer as a potential biomarker of responses to regorafenib treatment
Circulating cell‐free DNA (cfDNA) contains circulating tumor DNA (ctDNA), which can be obtained from serial liquid biopsies to enable tumor genome analysis throughout the course of treatment. We investigated cfDNA and mutant ctDNA as potential biomarkers to predict the best outcomes of regorafenib‐t...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-09-01
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| Series: | Molecular Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/1878-0261.12972 |
| _version_ | 1828946229975842816 |
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| author | Brice Pastor Thierry André Julie Henriques Isabelle Trouilloud Christophe Tournigand Marine Jary Thibault Mazard Christophe Louvet Simon Azan Audrey Bauer Benoit Roch Cynthia Sanchez Dewi Vernerey Alain R. Thierry Antoine Adenis |
| author_facet | Brice Pastor Thierry André Julie Henriques Isabelle Trouilloud Christophe Tournigand Marine Jary Thibault Mazard Christophe Louvet Simon Azan Audrey Bauer Benoit Roch Cynthia Sanchez Dewi Vernerey Alain R. Thierry Antoine Adenis |
| author_sort | Brice Pastor |
| collection | DOAJ |
| description | Circulating cell‐free DNA (cfDNA) contains circulating tumor DNA (ctDNA), which can be obtained from serial liquid biopsies to enable tumor genome analysis throughout the course of treatment. We investigated cfDNA and mutant ctDNA as potential biomarkers to predict the best outcomes of regorafenib‐treated metastatic colorectal cancer (mCRC) patients. We analyzed longitudinally collected plasma cfDNA of 43 mCRC patients prospectively enrolled in the phase II TEXCAN trial by IntPlex qPCR. Qualitative (KRAS, NRAS, BRAFV600E mutations) and quantitative (total cfDNA concentration, mutant ctDNA concentration, mutant ctDNA fraction) parameters were correlated with overall survival (OS) and progression‐free survival (PFS). When examined as classes or continuous variables, the concentrations of total cfDNA, mutant ctDNA, and, partly, mutant ctDNA fraction prior to regorafenib treatment correlated with OS. Patients with baseline cfDNA > 26 ng·mL−1 had shorter OS than those with cfDNA value below this threshold (4.0 vs 6.9 months; log‐rank P = 0.0366). Patients with baseline mutant ctDNA > 2 ng·mL−1 had shorter OS than those with mutant ctDNA below this threshold (log‐rank P = 0.0154). We show that pretreatment cfDNA and mutant ctDNA levels may identify mCRC patients that may benefit from regorafenib treatment. |
| first_indexed | 2024-12-14T05:06:58Z |
| format | Article |
| id | doaj.art-f02f440ca5a84aa39afc541bd361c7bf |
| institution | Directory Open Access Journal |
| issn | 1574-7891 1878-0261 |
| language | English |
| last_indexed | 2024-12-14T05:06:58Z |
| publishDate | 2021-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj.art-f02f440ca5a84aa39afc541bd361c7bf2022-12-21T23:16:05ZengWileyMolecular Oncology1574-78911878-02612021-09-011592401241110.1002/1878-0261.12972Monitoring levels of circulating cell‐free DNA in patients with metastatic colorectal cancer as a potential biomarker of responses to regorafenib treatmentBrice Pastor0Thierry André1Julie Henriques2Isabelle Trouilloud3Christophe Tournigand4Marine Jary5Thibault Mazard6Christophe Louvet7Simon Azan8Audrey Bauer9Benoit Roch10Cynthia Sanchez11Dewi Vernerey12Alain R. Thierry13Antoine Adenis14Institut de Recherche en Cancérologie de Montpellier (IRCM) INSERM Université de Montpellier Montpellier Cancer Institute (ICM) FranceDepartment of Medical Oncology Saint‐Antoine University Hospital Sorbonne University Paris FranceMethodology and Quality of Life Unit in Oncology Besançon University Hospital FranceDepartment of Medical Oncology Saint‐Antoine University Hospital Sorbonne University Paris FranceOncology Multidisciplinary Research Group (GERCOR) Paris FranceOncology Multidisciplinary Research Group (GERCOR) Paris FranceInstitut de Recherche en Cancérologie de Montpellier (IRCM) INSERM Université de Montpellier Montpellier Cancer Institute (ICM) FranceOncology Multidisciplinary Research Group (GERCOR) Paris FranceInstitut de Recherche en Cancérologie de Montpellier (IRCM) INSERM Université de Montpellier Montpellier Cancer Institute (ICM) FranceInstitut de Recherche en Cancérologie de Montpellier (IRCM) INSERM Université de Montpellier Montpellier Cancer Institute (ICM) FranceInstitut de Recherche en Cancérologie de Montpellier (IRCM) INSERM Université de Montpellier Montpellier Cancer Institute (ICM) FranceInstitut de Recherche en Cancérologie de Montpellier (IRCM) INSERM Université de Montpellier Montpellier Cancer Institute (ICM) FranceOncology Multidisciplinary Research Group (GERCOR) Paris FranceInstitut de Recherche en Cancérologie de Montpellier (IRCM) INSERM Université de Montpellier Montpellier Cancer Institute (ICM) FranceInstitut de Recherche en Cancérologie de Montpellier (IRCM) INSERM Université de Montpellier Montpellier Cancer Institute (ICM) FranceCirculating cell‐free DNA (cfDNA) contains circulating tumor DNA (ctDNA), which can be obtained from serial liquid biopsies to enable tumor genome analysis throughout the course of treatment. We investigated cfDNA and mutant ctDNA as potential biomarkers to predict the best outcomes of regorafenib‐treated metastatic colorectal cancer (mCRC) patients. We analyzed longitudinally collected plasma cfDNA of 43 mCRC patients prospectively enrolled in the phase II TEXCAN trial by IntPlex qPCR. Qualitative (KRAS, NRAS, BRAFV600E mutations) and quantitative (total cfDNA concentration, mutant ctDNA concentration, mutant ctDNA fraction) parameters were correlated with overall survival (OS) and progression‐free survival (PFS). When examined as classes or continuous variables, the concentrations of total cfDNA, mutant ctDNA, and, partly, mutant ctDNA fraction prior to regorafenib treatment correlated with OS. Patients with baseline cfDNA > 26 ng·mL−1 had shorter OS than those with cfDNA value below this threshold (4.0 vs 6.9 months; log‐rank P = 0.0366). Patients with baseline mutant ctDNA > 2 ng·mL−1 had shorter OS than those with mutant ctDNA below this threshold (log‐rank P = 0.0154). We show that pretreatment cfDNA and mutant ctDNA levels may identify mCRC patients that may benefit from regorafenib treatment.https://doi.org/10.1002/1878-0261.12972circulating DNAcolorectal cancerpredictive biomarkerregorafenibtumor response |
| spellingShingle | Brice Pastor Thierry André Julie Henriques Isabelle Trouilloud Christophe Tournigand Marine Jary Thibault Mazard Christophe Louvet Simon Azan Audrey Bauer Benoit Roch Cynthia Sanchez Dewi Vernerey Alain R. Thierry Antoine Adenis Monitoring levels of circulating cell‐free DNA in patients with metastatic colorectal cancer as a potential biomarker of responses to regorafenib treatment Molecular Oncology circulating DNA colorectal cancer predictive biomarker regorafenib tumor response |
| title | Monitoring levels of circulating cell‐free DNA in patients with metastatic colorectal cancer as a potential biomarker of responses to regorafenib treatment |
| title_full | Monitoring levels of circulating cell‐free DNA in patients with metastatic colorectal cancer as a potential biomarker of responses to regorafenib treatment |
| title_fullStr | Monitoring levels of circulating cell‐free DNA in patients with metastatic colorectal cancer as a potential biomarker of responses to regorafenib treatment |
| title_full_unstemmed | Monitoring levels of circulating cell‐free DNA in patients with metastatic colorectal cancer as a potential biomarker of responses to regorafenib treatment |
| title_short | Monitoring levels of circulating cell‐free DNA in patients with metastatic colorectal cancer as a potential biomarker of responses to regorafenib treatment |
| title_sort | monitoring levels of circulating cell free dna in patients with metastatic colorectal cancer as a potential biomarker of responses to regorafenib treatment |
| topic | circulating DNA colorectal cancer predictive biomarker regorafenib tumor response |
| url | https://doi.org/10.1002/1878-0261.12972 |
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