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Early Change in FDG-PET Signal and Plasma Cell-Free DNA Level Predicts Erlotinib Response in EGFR Wild-Type NSCLC Patients()

INTRODUCTION: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are a treatment option in the second- or third-line palliative setting in EGFR wild-type (wt) non–small cell lung cancer (NSCLC) patients. However, response rates are low, and only approximately 25% will achieve...

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Autores principales: Winther-Larsen, Anne, Fledelius, Joan, Demuth, Christina, Bylov, Catharina M, Meldgaard, Peter, Sorensen, Boe S
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5094375/
https://www.ncbi.nlm.nih.gov/pubmed/27816687
http://dx.doi.org/10.1016/j.tranon.2016.09.003
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author Winther-Larsen, Anne
Fledelius, Joan
Demuth, Christina
Bylov, Catharina M
Meldgaard, Peter
Sorensen, Boe S
author_facet Winther-Larsen, Anne
Fledelius, Joan
Demuth, Christina
Bylov, Catharina M
Meldgaard, Peter
Sorensen, Boe S
author_sort Winther-Larsen, Anne
collection PubMed
description INTRODUCTION: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are a treatment option in the second- or third-line palliative setting in EGFR wild-type (wt) non–small cell lung cancer (NSCLC) patients. However, response rates are low, and only approximately 25% will achieve disease control. Early prediction of treatment resistance could accelerate discontinuation of ineffective treatment and reduce unnecessary toxicity. In this study, we evaluated early changes on 18F-fluoro-D-glucose (F-18-FDG) positron emission tomography/computed tomography (PET/CT) and in total plasma cell-free DNA (cfDNA) as markers of erlotinib response in EGFR-wt patients. METHODS: F-18-FDG-PET/CT scans and blood samples were obtained prior to erlotinib initiation and were repeated after 1 week (PET/CT) and 1 to 4 weeks (blood sample) of treatment. Level of cfDNA was measured by droplet digital polymerase chain reaction. Percentage change (%∆) in SUL(peak) and total lesion glycolysis (TLG) on FDG-PET/CT and in plasma cfDNA was correlated to radiological response, progression-free survival (PFS), and overall survival (OS). RESULTS: Fifty patients were prospectively enrolled. A significant correlation was found between CT response and %∆TLG (P = .003). All patients with early metabolic progression showed radiological progression. Increased %∆TLG and %∆cfDNA were significantly correlated with shorter PFS (P = .002 and P = .004, respectively) and OS (P = .009 and P = .009, respectively). Multivariate analysis indicated %∆cfDNA to be the strongest predictor of OS. CONCLUSION: Early increase in TLG on F-18-FDG-PET/CT correlates with radiological progression, and shorter PFS and OS. Early increase in cfDNA predicts shorter PFS and OS. Both assessments are promising tools for early detection of nonresponders and reduced OS in TKI-treated EGFR-wt NSCLC patients.
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spelling pubmed-50943752016-11-04 Early Change in FDG-PET Signal and Plasma Cell-Free DNA Level Predicts Erlotinib Response in EGFR Wild-Type NSCLC Patients() Winther-Larsen, Anne Fledelius, Joan Demuth, Christina Bylov, Catharina M Meldgaard, Peter Sorensen, Boe S Transl Oncol Original article INTRODUCTION: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are a treatment option in the second- or third-line palliative setting in EGFR wild-type (wt) non–small cell lung cancer (NSCLC) patients. However, response rates are low, and only approximately 25% will achieve disease control. Early prediction of treatment resistance could accelerate discontinuation of ineffective treatment and reduce unnecessary toxicity. In this study, we evaluated early changes on 18F-fluoro-D-glucose (F-18-FDG) positron emission tomography/computed tomography (PET/CT) and in total plasma cell-free DNA (cfDNA) as markers of erlotinib response in EGFR-wt patients. METHODS: F-18-FDG-PET/CT scans and blood samples were obtained prior to erlotinib initiation and were repeated after 1 week (PET/CT) and 1 to 4 weeks (blood sample) of treatment. Level of cfDNA was measured by droplet digital polymerase chain reaction. Percentage change (%∆) in SUL(peak) and total lesion glycolysis (TLG) on FDG-PET/CT and in plasma cfDNA was correlated to radiological response, progression-free survival (PFS), and overall survival (OS). RESULTS: Fifty patients were prospectively enrolled. A significant correlation was found between CT response and %∆TLG (P = .003). All patients with early metabolic progression showed radiological progression. Increased %∆TLG and %∆cfDNA were significantly correlated with shorter PFS (P = .002 and P = .004, respectively) and OS (P = .009 and P = .009, respectively). Multivariate analysis indicated %∆cfDNA to be the strongest predictor of OS. CONCLUSION: Early increase in TLG on F-18-FDG-PET/CT correlates with radiological progression, and shorter PFS and OS. Early increase in cfDNA predicts shorter PFS and OS. Both assessments are promising tools for early detection of nonresponders and reduced OS in TKI-treated EGFR-wt NSCLC patients. Neoplasia Press 2016-10-29 /pmc/articles/PMC5094375/ /pubmed/27816687 http://dx.doi.org/10.1016/j.tranon.2016.09.003 Text en © 2016 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original article
Winther-Larsen, Anne
Fledelius, Joan
Demuth, Christina
Bylov, Catharina M
Meldgaard, Peter
Sorensen, Boe S
Early Change in FDG-PET Signal and Plasma Cell-Free DNA Level Predicts Erlotinib Response in EGFR Wild-Type NSCLC Patients()
title Early Change in FDG-PET Signal and Plasma Cell-Free DNA Level Predicts Erlotinib Response in EGFR Wild-Type NSCLC Patients()
title_full Early Change in FDG-PET Signal and Plasma Cell-Free DNA Level Predicts Erlotinib Response in EGFR Wild-Type NSCLC Patients()
title_fullStr Early Change in FDG-PET Signal and Plasma Cell-Free DNA Level Predicts Erlotinib Response in EGFR Wild-Type NSCLC Patients()
title_full_unstemmed Early Change in FDG-PET Signal and Plasma Cell-Free DNA Level Predicts Erlotinib Response in EGFR Wild-Type NSCLC Patients()
title_short Early Change in FDG-PET Signal and Plasma Cell-Free DNA Level Predicts Erlotinib Response in EGFR Wild-Type NSCLC Patients()
title_sort early change in fdg-pet signal and plasma cell-free dna level predicts erlotinib response in egfr wild-type nsclc patients()
topic Original article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5094375/
https://www.ncbi.nlm.nih.gov/pubmed/27816687
http://dx.doi.org/10.1016/j.tranon.2016.09.003
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