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Detection and Monitoring of Tumor-Derived Mutations in Circulating Tumor DNA Using the UltraSEEK Lung Panel on the MassARRAY System in Metastatic Non-Small Cell Lung Cancer Patients

Analysis of circulating tumor DNA (ctDNA) is a potential minimally invasive molecular tool to guide treatment decision-making and disease monitoring. A suitable diagnostic-grade platform is required for the detection of tumor-specific mutations with high sensitivity in the circulating cell-free DNA...

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Autores principales: van der Leest, Paul, Janning, Melanie, Rifaela, Naomi, Azpurua, Maria L. Aguirre, Kropidlowski, Jolanthe, Loges, Sonja, Lozano, Nicolas, Sartori, Alexander, Irwin, Darryl, Lamy, Pierre-Jean, Hiltermann, T. Jeroen N., Groen, Harry J. M., Pantel, Klaus, van Kempen, Léon C., Wikman, Harriet, Schuuring, Ed
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10487510/
https://www.ncbi.nlm.nih.gov/pubmed/37686200
http://dx.doi.org/10.3390/ijms241713390
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author van der Leest, Paul
Janning, Melanie
Rifaela, Naomi
Azpurua, Maria L. Aguirre
Kropidlowski, Jolanthe
Loges, Sonja
Lozano, Nicolas
Sartori, Alexander
Irwin, Darryl
Lamy, Pierre-Jean
Hiltermann, T. Jeroen N.
Groen, Harry J. M.
Pantel, Klaus
van Kempen, Léon C.
Wikman, Harriet
Schuuring, Ed
author_facet van der Leest, Paul
Janning, Melanie
Rifaela, Naomi
Azpurua, Maria L. Aguirre
Kropidlowski, Jolanthe
Loges, Sonja
Lozano, Nicolas
Sartori, Alexander
Irwin, Darryl
Lamy, Pierre-Jean
Hiltermann, T. Jeroen N.
Groen, Harry J. M.
Pantel, Klaus
van Kempen, Léon C.
Wikman, Harriet
Schuuring, Ed
author_sort van der Leest, Paul
collection PubMed
description Analysis of circulating tumor DNA (ctDNA) is a potential minimally invasive molecular tool to guide treatment decision-making and disease monitoring. A suitable diagnostic-grade platform is required for the detection of tumor-specific mutations with high sensitivity in the circulating cell-free DNA (ccfDNA) of cancer patients. In this multicenter study, the ccfDNA of 72 patients treated for advanced-stage non-small cell lung cancer (NSCLC) was evaluated using the UltraSEEK(®) Lung Panel on the MassARRAY(®) System, covering 73 hotspot mutations in EGFR, KRAS, BRAF, ERBB2, and PIK3CA against mutation-specific droplet digital PCR (ddPCR) and routine tumor tissue NGS. Variant detection accuracy at primary diagnosis and during disease progression, and ctDNA dynamics as a marker of treatment efficacy, were analyzed. A multicenter evaluation using reference material demonstrated an overall detection rate of over 90% for variant allele frequencies (VAFs) > 0.5%, irrespective of ccfDNA input. A comparison of UltraSEEK(®) and ddPCR analyses revealed a 90% concordance. An 80% concordance between therapeutically targetable mutations detected in tumor tissue NGS and ccfDNA UltraSEEK(®) analysis at baseline was observed. Nine of 84 (11%) tumor tissue mutations were not covered by UltraSEEK(®). A decrease in ctDNA levels at 4–6 weeks after treatment initiation detected with UltraSEEK(®) correlated with prolonged median PFS (46 vs. 6 weeks; p < 0.05) and OS (145 vs. 30 weeks; p < 0.01). Using plasma-derived ccfDNA, the UltraSEEK(®) Lung Panel with a mid-density set of the most common predictive markers for NSCLC is an alternative tool to detect mutations both at diagnosis and during disease progression and to monitor treatment response.
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spelling pubmed-104875102023-09-09 Detection and Monitoring of Tumor-Derived Mutations in Circulating Tumor DNA Using the UltraSEEK Lung Panel on the MassARRAY System in Metastatic Non-Small Cell Lung Cancer Patients van der Leest, Paul Janning, Melanie Rifaela, Naomi Azpurua, Maria L. Aguirre Kropidlowski, Jolanthe Loges, Sonja Lozano, Nicolas Sartori, Alexander Irwin, Darryl Lamy, Pierre-Jean Hiltermann, T. Jeroen N. Groen, Harry J. M. Pantel, Klaus van Kempen, Léon C. Wikman, Harriet Schuuring, Ed Int J Mol Sci Article Analysis of circulating tumor DNA (ctDNA) is a potential minimally invasive molecular tool to guide treatment decision-making and disease monitoring. A suitable diagnostic-grade platform is required for the detection of tumor-specific mutations with high sensitivity in the circulating cell-free DNA (ccfDNA) of cancer patients. In this multicenter study, the ccfDNA of 72 patients treated for advanced-stage non-small cell lung cancer (NSCLC) was evaluated using the UltraSEEK(®) Lung Panel on the MassARRAY(®) System, covering 73 hotspot mutations in EGFR, KRAS, BRAF, ERBB2, and PIK3CA against mutation-specific droplet digital PCR (ddPCR) and routine tumor tissue NGS. Variant detection accuracy at primary diagnosis and during disease progression, and ctDNA dynamics as a marker of treatment efficacy, were analyzed. A multicenter evaluation using reference material demonstrated an overall detection rate of over 90% for variant allele frequencies (VAFs) > 0.5%, irrespective of ccfDNA input. A comparison of UltraSEEK(®) and ddPCR analyses revealed a 90% concordance. An 80% concordance between therapeutically targetable mutations detected in tumor tissue NGS and ccfDNA UltraSEEK(®) analysis at baseline was observed. Nine of 84 (11%) tumor tissue mutations were not covered by UltraSEEK(®). A decrease in ctDNA levels at 4–6 weeks after treatment initiation detected with UltraSEEK(®) correlated with prolonged median PFS (46 vs. 6 weeks; p < 0.05) and OS (145 vs. 30 weeks; p < 0.01). Using plasma-derived ccfDNA, the UltraSEEK(®) Lung Panel with a mid-density set of the most common predictive markers for NSCLC is an alternative tool to detect mutations both at diagnosis and during disease progression and to monitor treatment response. MDPI 2023-08-29 /pmc/articles/PMC10487510/ /pubmed/37686200 http://dx.doi.org/10.3390/ijms241713390 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
van der Leest, Paul
Janning, Melanie
Rifaela, Naomi
Azpurua, Maria L. Aguirre
Kropidlowski, Jolanthe
Loges, Sonja
Lozano, Nicolas
Sartori, Alexander
Irwin, Darryl
Lamy, Pierre-Jean
Hiltermann, T. Jeroen N.
Groen, Harry J. M.
Pantel, Klaus
van Kempen, Léon C.
Wikman, Harriet
Schuuring, Ed
Detection and Monitoring of Tumor-Derived Mutations in Circulating Tumor DNA Using the UltraSEEK Lung Panel on the MassARRAY System in Metastatic Non-Small Cell Lung Cancer Patients
title Detection and Monitoring of Tumor-Derived Mutations in Circulating Tumor DNA Using the UltraSEEK Lung Panel on the MassARRAY System in Metastatic Non-Small Cell Lung Cancer Patients
title_full Detection and Monitoring of Tumor-Derived Mutations in Circulating Tumor DNA Using the UltraSEEK Lung Panel on the MassARRAY System in Metastatic Non-Small Cell Lung Cancer Patients
title_fullStr Detection and Monitoring of Tumor-Derived Mutations in Circulating Tumor DNA Using the UltraSEEK Lung Panel on the MassARRAY System in Metastatic Non-Small Cell Lung Cancer Patients
title_full_unstemmed Detection and Monitoring of Tumor-Derived Mutations in Circulating Tumor DNA Using the UltraSEEK Lung Panel on the MassARRAY System in Metastatic Non-Small Cell Lung Cancer Patients
title_short Detection and Monitoring of Tumor-Derived Mutations in Circulating Tumor DNA Using the UltraSEEK Lung Panel on the MassARRAY System in Metastatic Non-Small Cell Lung Cancer Patients
title_sort detection and monitoring of tumor-derived mutations in circulating tumor dna using the ultraseek lung panel on the massarray system in metastatic non-small cell lung cancer patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10487510/
https://www.ncbi.nlm.nih.gov/pubmed/37686200
http://dx.doi.org/10.3390/ijms241713390
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