Cargando…

The Dynamic Use of EGFR Mutation Analysis in Cell-Free DNA as a Follow-Up Biomarker during Different Treatment Lines in Non-Small-Cell Lung Cancer Patients

Epidermal growth factor receptor (EGFR) mutational testing in advanced non-small-cell lung cancer (NSCLC) is usually performed in tumor tissue, although cfDNA (cell-free DNA) could be an alternative. We evaluated EGFR mutations in cfDNA as a complementary tool in patients, who had already known EGFR...

Descripción completa

Detalles Bibliográficos
Autores principales: Macías, Mónica, Alegre, Estibaliz, Alkorta-Aranburu, Gorka, Patiño-García, Ana, Mateos, Beatriz, Andueza, Maria P., Gúrpide, Alfonso, Lopez-Picazo, Jose M., Gil-Bazo, Ignacio, Perez-Gracia, Jose L., González, Álvaro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6364099/
https://www.ncbi.nlm.nih.gov/pubmed/30809319
http://dx.doi.org/10.1155/2019/7954921
_version_ 1783393199394390016
author Macías, Mónica
Alegre, Estibaliz
Alkorta-Aranburu, Gorka
Patiño-García, Ana
Mateos, Beatriz
Andueza, Maria P.
Gúrpide, Alfonso
Lopez-Picazo, Jose M.
Gil-Bazo, Ignacio
Perez-Gracia, Jose L.
González, Álvaro
author_facet Macías, Mónica
Alegre, Estibaliz
Alkorta-Aranburu, Gorka
Patiño-García, Ana
Mateos, Beatriz
Andueza, Maria P.
Gúrpide, Alfonso
Lopez-Picazo, Jose M.
Gil-Bazo, Ignacio
Perez-Gracia, Jose L.
González, Álvaro
author_sort Macías, Mónica
collection PubMed
description Epidermal growth factor receptor (EGFR) mutational testing in advanced non-small-cell lung cancer (NSCLC) is usually performed in tumor tissue, although cfDNA (cell-free DNA) could be an alternative. We evaluated EGFR mutations in cfDNA as a complementary tool in patients, who had already known EGFR mutations in tumor tissue and were treated with either EGFR-tyrosine kinase inhibitors (TKIs) or chemotherapy. We obtained plasma samples from 21 advanced NSCLC patients with known EGFR tumor mutations, before and during therapy with EGFR-TKIs and/or chemotherapy. cfDNA was isolated and EGFR mutations were analyzed with the multiple targeted cobas EGFR Mutation Test v2. EGFR mutations were detected at baseline in cfDNA from 57% of patients. The semiquantitative index (SQI) significantly decreased from the baseline (median = 11, IQR = 9.5-13) to the best response (median = 0, IQR = 0-0, p < 0.01), followed by a significant increase at progression (median = 11, IQR = 11-15, p < 0.01) in patients treated with either EGFR-TKIs or chemotherapy. The SQI obtained with the cobas EGFR Mutation Test v2 did not correlate with the concentration in copies/mL determined by droplet digital PCR. Resistance mutation p.T790M was observed at progression in patients with either type of treatment. In conclusion, cfDNA multiple targeted EGFR mutation analysis is useful for treatment monitoring in tissue of EGFR-positive NSCLC patients independently of the drug received.
format Online
Article
Text
id pubmed-6364099
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Hindawi
record_format MEDLINE/PubMed
spelling pubmed-63640992019-02-26 The Dynamic Use of EGFR Mutation Analysis in Cell-Free DNA as a Follow-Up Biomarker during Different Treatment Lines in Non-Small-Cell Lung Cancer Patients Macías, Mónica Alegre, Estibaliz Alkorta-Aranburu, Gorka Patiño-García, Ana Mateos, Beatriz Andueza, Maria P. Gúrpide, Alfonso Lopez-Picazo, Jose M. Gil-Bazo, Ignacio Perez-Gracia, Jose L. González, Álvaro Dis Markers Research Article Epidermal growth factor receptor (EGFR) mutational testing in advanced non-small-cell lung cancer (NSCLC) is usually performed in tumor tissue, although cfDNA (cell-free DNA) could be an alternative. We evaluated EGFR mutations in cfDNA as a complementary tool in patients, who had already known EGFR mutations in tumor tissue and were treated with either EGFR-tyrosine kinase inhibitors (TKIs) or chemotherapy. We obtained plasma samples from 21 advanced NSCLC patients with known EGFR tumor mutations, before and during therapy with EGFR-TKIs and/or chemotherapy. cfDNA was isolated and EGFR mutations were analyzed with the multiple targeted cobas EGFR Mutation Test v2. EGFR mutations were detected at baseline in cfDNA from 57% of patients. The semiquantitative index (SQI) significantly decreased from the baseline (median = 11, IQR = 9.5-13) to the best response (median = 0, IQR = 0-0, p < 0.01), followed by a significant increase at progression (median = 11, IQR = 11-15, p < 0.01) in patients treated with either EGFR-TKIs or chemotherapy. The SQI obtained with the cobas EGFR Mutation Test v2 did not correlate with the concentration in copies/mL determined by droplet digital PCR. Resistance mutation p.T790M was observed at progression in patients with either type of treatment. In conclusion, cfDNA multiple targeted EGFR mutation analysis is useful for treatment monitoring in tissue of EGFR-positive NSCLC patients independently of the drug received. Hindawi 2019-01-23 /pmc/articles/PMC6364099/ /pubmed/30809319 http://dx.doi.org/10.1155/2019/7954921 Text en Copyright © 2019 Mónica Macías et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Macías, Mónica
Alegre, Estibaliz
Alkorta-Aranburu, Gorka
Patiño-García, Ana
Mateos, Beatriz
Andueza, Maria P.
Gúrpide, Alfonso
Lopez-Picazo, Jose M.
Gil-Bazo, Ignacio
Perez-Gracia, Jose L.
González, Álvaro
The Dynamic Use of EGFR Mutation Analysis in Cell-Free DNA as a Follow-Up Biomarker during Different Treatment Lines in Non-Small-Cell Lung Cancer Patients
title The Dynamic Use of EGFR Mutation Analysis in Cell-Free DNA as a Follow-Up Biomarker during Different Treatment Lines in Non-Small-Cell Lung Cancer Patients
title_full The Dynamic Use of EGFR Mutation Analysis in Cell-Free DNA as a Follow-Up Biomarker during Different Treatment Lines in Non-Small-Cell Lung Cancer Patients
title_fullStr The Dynamic Use of EGFR Mutation Analysis in Cell-Free DNA as a Follow-Up Biomarker during Different Treatment Lines in Non-Small-Cell Lung Cancer Patients
title_full_unstemmed The Dynamic Use of EGFR Mutation Analysis in Cell-Free DNA as a Follow-Up Biomarker during Different Treatment Lines in Non-Small-Cell Lung Cancer Patients
title_short The Dynamic Use of EGFR Mutation Analysis in Cell-Free DNA as a Follow-Up Biomarker during Different Treatment Lines in Non-Small-Cell Lung Cancer Patients
title_sort dynamic use of egfr mutation analysis in cell-free dna as a follow-up biomarker during different treatment lines in non-small-cell lung cancer patients
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6364099/
https://www.ncbi.nlm.nih.gov/pubmed/30809319
http://dx.doi.org/10.1155/2019/7954921
work_keys_str_mv AT maciasmonica thedynamicuseofegfrmutationanalysisincellfreednaasafollowupbiomarkerduringdifferenttreatmentlinesinnonsmallcelllungcancerpatients
AT alegreestibaliz thedynamicuseofegfrmutationanalysisincellfreednaasafollowupbiomarkerduringdifferenttreatmentlinesinnonsmallcelllungcancerpatients
AT alkortaaranburugorka thedynamicuseofegfrmutationanalysisincellfreednaasafollowupbiomarkerduringdifferenttreatmentlinesinnonsmallcelllungcancerpatients
AT patinogarciaana thedynamicuseofegfrmutationanalysisincellfreednaasafollowupbiomarkerduringdifferenttreatmentlinesinnonsmallcelllungcancerpatients
AT mateosbeatriz thedynamicuseofegfrmutationanalysisincellfreednaasafollowupbiomarkerduringdifferenttreatmentlinesinnonsmallcelllungcancerpatients
AT anduezamariap thedynamicuseofegfrmutationanalysisincellfreednaasafollowupbiomarkerduringdifferenttreatmentlinesinnonsmallcelllungcancerpatients
AT gurpidealfonso thedynamicuseofegfrmutationanalysisincellfreednaasafollowupbiomarkerduringdifferenttreatmentlinesinnonsmallcelllungcancerpatients
AT lopezpicazojosem thedynamicuseofegfrmutationanalysisincellfreednaasafollowupbiomarkerduringdifferenttreatmentlinesinnonsmallcelllungcancerpatients
AT gilbazoignacio thedynamicuseofegfrmutationanalysisincellfreednaasafollowupbiomarkerduringdifferenttreatmentlinesinnonsmallcelllungcancerpatients
AT perezgraciajosel thedynamicuseofegfrmutationanalysisincellfreednaasafollowupbiomarkerduringdifferenttreatmentlinesinnonsmallcelllungcancerpatients
AT gonzalezalvaro thedynamicuseofegfrmutationanalysisincellfreednaasafollowupbiomarkerduringdifferenttreatmentlinesinnonsmallcelllungcancerpatients
AT maciasmonica dynamicuseofegfrmutationanalysisincellfreednaasafollowupbiomarkerduringdifferenttreatmentlinesinnonsmallcelllungcancerpatients
AT alegreestibaliz dynamicuseofegfrmutationanalysisincellfreednaasafollowupbiomarkerduringdifferenttreatmentlinesinnonsmallcelllungcancerpatients
AT alkortaaranburugorka dynamicuseofegfrmutationanalysisincellfreednaasafollowupbiomarkerduringdifferenttreatmentlinesinnonsmallcelllungcancerpatients
AT patinogarciaana dynamicuseofegfrmutationanalysisincellfreednaasafollowupbiomarkerduringdifferenttreatmentlinesinnonsmallcelllungcancerpatients
AT mateosbeatriz dynamicuseofegfrmutationanalysisincellfreednaasafollowupbiomarkerduringdifferenttreatmentlinesinnonsmallcelllungcancerpatients
AT anduezamariap dynamicuseofegfrmutationanalysisincellfreednaasafollowupbiomarkerduringdifferenttreatmentlinesinnonsmallcelllungcancerpatients
AT gurpidealfonso dynamicuseofegfrmutationanalysisincellfreednaasafollowupbiomarkerduringdifferenttreatmentlinesinnonsmallcelllungcancerpatients
AT lopezpicazojosem dynamicuseofegfrmutationanalysisincellfreednaasafollowupbiomarkerduringdifferenttreatmentlinesinnonsmallcelllungcancerpatients
AT gilbazoignacio dynamicuseofegfrmutationanalysisincellfreednaasafollowupbiomarkerduringdifferenttreatmentlinesinnonsmallcelllungcancerpatients
AT perezgraciajosel dynamicuseofegfrmutationanalysisincellfreednaasafollowupbiomarkerduringdifferenttreatmentlinesinnonsmallcelllungcancerpatients
AT gonzalezalvaro dynamicuseofegfrmutationanalysisincellfreednaasafollowupbiomarkerduringdifferenttreatmentlinesinnonsmallcelllungcancerpatients