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The Clinically Actionable Molecular Profile of Early versus Late-Stage Non-Small Cell Lung Cancer, an Individual Age and Sex Propensity-Matched Pair Analysis

Background: Despite meticulous surgery for non-small cell lung cancer (NSCLC), relapse is as high as 70% at 5 years. Many institutions do not conduct reflexive molecular testing on early stage specimens, although targeted gene therapy may extend life by years in the event of recurrence. This ultimat...

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Autores principales: McGuire, Anna L., McConechy, Melissa K., Melosky, Barb L., English, John C., Choi, James J., Peng, Defen, Yee, John, Furman, Benjamin L. S., Aguirre Hernandez, Rosalia, Feijao, Pedro, Mulder, David, Hughesman, Curtis, Yip, Stephen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9031556/
https://www.ncbi.nlm.nih.gov/pubmed/35448189
http://dx.doi.org/10.3390/curroncol29040215
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author McGuire, Anna L.
McConechy, Melissa K.
Melosky, Barb L.
English, John C.
Choi, James J.
Peng, Defen
Yee, John
Furman, Benjamin L. S.
Aguirre Hernandez, Rosalia
Feijao, Pedro
Mulder, David
Hughesman, Curtis
Yip, Stephen
author_facet McGuire, Anna L.
McConechy, Melissa K.
Melosky, Barb L.
English, John C.
Choi, James J.
Peng, Defen
Yee, John
Furman, Benjamin L. S.
Aguirre Hernandez, Rosalia
Feijao, Pedro
Mulder, David
Hughesman, Curtis
Yip, Stephen
author_sort McGuire, Anna L.
collection PubMed
description Background: Despite meticulous surgery for non-small cell lung cancer (NSCLC), relapse is as high as 70% at 5 years. Many institutions do not conduct reflexive molecular testing on early stage specimens, although targeted gene therapy may extend life by years in the event of recurrence. This ultimately delays definitive treatment with additional biopsy risking suboptimal tissue acquisition and quality for molecular testing. Objective: To compare molecular profiles of genetic alterations in early and late NSCLC to provide evidence that reflexive molecular testing provides clinically valuable information. Methods: A single-center propensity matched retrospective analysis was conducted using prospectively collected data. Adults with early and late-stage NSCLC had tissue subject to targeted panel-based NGS. Frequencies of putative drivers were compared, with 1:3 matching on the propensity score; p < 0.05 deemed statistically significant. Results: In total, 635 NSCLC patients underwent NGS (59 early, 576 late); 276 (43.5%) females; age 70.9 (±10.2) years; never smokers 140 (22.0%); 527 (83.0%) adenocarcinomas. Unadjusted frequencies of EGFR mutations were higher in the early cohort (30% vs. 18%). Following adjustment for sex and smoking status, similar frequencies for both early and late NSCLC were observed for variants in EGFR, KRAS, ALK, MET, and ROS1. Conclusion: The frequency of clinically actionable variants in early and late-stage NSCLC was found to be similar, providing evidence that molecular profiling should be performed on surgical specimens. This pre-determined profile is essential to avoid treatment delay for patients who will derive clinical benefit from targeted systemic therapy, in the high likelihood of subsequent relapse.
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spelling pubmed-90315562022-04-23 The Clinically Actionable Molecular Profile of Early versus Late-Stage Non-Small Cell Lung Cancer, an Individual Age and Sex Propensity-Matched Pair Analysis McGuire, Anna L. McConechy, Melissa K. Melosky, Barb L. English, John C. Choi, James J. Peng, Defen Yee, John Furman, Benjamin L. S. Aguirre Hernandez, Rosalia Feijao, Pedro Mulder, David Hughesman, Curtis Yip, Stephen Curr Oncol Article Background: Despite meticulous surgery for non-small cell lung cancer (NSCLC), relapse is as high as 70% at 5 years. Many institutions do not conduct reflexive molecular testing on early stage specimens, although targeted gene therapy may extend life by years in the event of recurrence. This ultimately delays definitive treatment with additional biopsy risking suboptimal tissue acquisition and quality for molecular testing. Objective: To compare molecular profiles of genetic alterations in early and late NSCLC to provide evidence that reflexive molecular testing provides clinically valuable information. Methods: A single-center propensity matched retrospective analysis was conducted using prospectively collected data. Adults with early and late-stage NSCLC had tissue subject to targeted panel-based NGS. Frequencies of putative drivers were compared, with 1:3 matching on the propensity score; p < 0.05 deemed statistically significant. Results: In total, 635 NSCLC patients underwent NGS (59 early, 576 late); 276 (43.5%) females; age 70.9 (±10.2) years; never smokers 140 (22.0%); 527 (83.0%) adenocarcinomas. Unadjusted frequencies of EGFR mutations were higher in the early cohort (30% vs. 18%). Following adjustment for sex and smoking status, similar frequencies for both early and late NSCLC were observed for variants in EGFR, KRAS, ALK, MET, and ROS1. Conclusion: The frequency of clinically actionable variants in early and late-stage NSCLC was found to be similar, providing evidence that molecular profiling should be performed on surgical specimens. This pre-determined profile is essential to avoid treatment delay for patients who will derive clinical benefit from targeted systemic therapy, in the high likelihood of subsequent relapse. MDPI 2022-04-11 /pmc/articles/PMC9031556/ /pubmed/35448189 http://dx.doi.org/10.3390/curroncol29040215 Text en © 2022 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
McGuire, Anna L.
McConechy, Melissa K.
Melosky, Barb L.
English, John C.
Choi, James J.
Peng, Defen
Yee, John
Furman, Benjamin L. S.
Aguirre Hernandez, Rosalia
Feijao, Pedro
Mulder, David
Hughesman, Curtis
Yip, Stephen
The Clinically Actionable Molecular Profile of Early versus Late-Stage Non-Small Cell Lung Cancer, an Individual Age and Sex Propensity-Matched Pair Analysis
title The Clinically Actionable Molecular Profile of Early versus Late-Stage Non-Small Cell Lung Cancer, an Individual Age and Sex Propensity-Matched Pair Analysis
title_full The Clinically Actionable Molecular Profile of Early versus Late-Stage Non-Small Cell Lung Cancer, an Individual Age and Sex Propensity-Matched Pair Analysis
title_fullStr The Clinically Actionable Molecular Profile of Early versus Late-Stage Non-Small Cell Lung Cancer, an Individual Age and Sex Propensity-Matched Pair Analysis
title_full_unstemmed The Clinically Actionable Molecular Profile of Early versus Late-Stage Non-Small Cell Lung Cancer, an Individual Age and Sex Propensity-Matched Pair Analysis
title_short The Clinically Actionable Molecular Profile of Early versus Late-Stage Non-Small Cell Lung Cancer, an Individual Age and Sex Propensity-Matched Pair Analysis
title_sort clinically actionable molecular profile of early versus late-stage non-small cell lung cancer, an individual age and sex propensity-matched pair analysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9031556/
https://www.ncbi.nlm.nih.gov/pubmed/35448189
http://dx.doi.org/10.3390/curroncol29040215
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