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Association of Circulating Tumor DNA Testing Before Tissue Diagnosis With Time to Treatment Among Patients With Suspected Advanced Lung Cancer: The ACCELERATE Nonrandomized Clinical Trial

IMPORTANCE: Liquid biopsy has emerged as a complement to tumor tissue profiling for advanced non–small cell lung cancer (NSCLC). The optimal way to integrate liquid biopsy into the diagnostic algorithm for patients with newly diagnosed advanced NSCLC remains unclear. OBJECTIVE: To evaluate the use o...

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Autores principales: García-Pardo, Miguel, Czarnecka-Kujawa, Kasia, Law, Jennifer H., Salvarrey, Alexandra M., Fernandes, Roxanne, Fan, Zhen J., Waddell, Thomas K., Yasufuku, Kazuhiro, Liu, Geoffrey, Donahoe, Laura L., Pierre, Andrew, Le, Lisa W., Gunasegaran, Tharsiga, Ghumman, Noor, Shepherd, Frances A., Bradbury, Penelope A., Sacher, Adrian G., Schmid, Sabine, Corke, Lucy, Feng, Jamie, Stockley, Tracy, Pal, Prodipto, Rogalla, Patrik, Pipinikas, Christodoulos, Howarth, Karen, Ambasager, Bana, Mezquita, Laura, Tsao, Ming S., Leighl, Natasha B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Medical Association 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10369925/
https://www.ncbi.nlm.nih.gov/pubmed/37490292
http://dx.doi.org/10.1001/jamanetworkopen.2023.25332
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author García-Pardo, Miguel
Czarnecka-Kujawa, Kasia
Law, Jennifer H.
Salvarrey, Alexandra M.
Fernandes, Roxanne
Fan, Zhen J.
Waddell, Thomas K.
Yasufuku, Kazuhiro
Liu, Geoffrey
Donahoe, Laura L.
Pierre, Andrew
Le, Lisa W.
Gunasegaran, Tharsiga
Ghumman, Noor
Shepherd, Frances A.
Bradbury, Penelope A.
Sacher, Adrian G.
Schmid, Sabine
Corke, Lucy
Feng, Jamie
Stockley, Tracy
Pal, Prodipto
Rogalla, Patrik
Pipinikas, Christodoulos
Howarth, Karen
Ambasager, Bana
Mezquita, Laura
Tsao, Ming S.
Leighl, Natasha B.
author_facet García-Pardo, Miguel
Czarnecka-Kujawa, Kasia
Law, Jennifer H.
Salvarrey, Alexandra M.
Fernandes, Roxanne
Fan, Zhen J.
Waddell, Thomas K.
Yasufuku, Kazuhiro
Liu, Geoffrey
Donahoe, Laura L.
Pierre, Andrew
Le, Lisa W.
Gunasegaran, Tharsiga
Ghumman, Noor
Shepherd, Frances A.
Bradbury, Penelope A.
Sacher, Adrian G.
Schmid, Sabine
Corke, Lucy
Feng, Jamie
Stockley, Tracy
Pal, Prodipto
Rogalla, Patrik
Pipinikas, Christodoulos
Howarth, Karen
Ambasager, Bana
Mezquita, Laura
Tsao, Ming S.
Leighl, Natasha B.
author_sort García-Pardo, Miguel
collection PubMed
description IMPORTANCE: Liquid biopsy has emerged as a complement to tumor tissue profiling for advanced non–small cell lung cancer (NSCLC). The optimal way to integrate liquid biopsy into the diagnostic algorithm for patients with newly diagnosed advanced NSCLC remains unclear. OBJECTIVE: To evaluate the use of circulating tumor DNA (ctDNA) genotyping before tissue diagnosis among patients with suspected advanced NSCLC and its association with time to treatment. DESIGN, SETTING, AND PARTICIPANTS: This single-group nonrandomized clinical trial was conducted among 150 patients at the Princess Margaret Cancer Centre–University Health Network (Toronto, Ontario, Canada) between July 1, 2021, and November 30, 2022. Patients referred for investigation and diagnosis of lung cancer were eligible if they had radiologic evidence of advanced lung cancer prior to a tissue diagnosis. INTERVENTIONS: Patients underwent plasma ctDNA testing with a next-generation sequencing (NGS) assay before lung cancer diagnosis. Diagnostic biopsy and tissue NGS were performed per standard of care. MAIN OUTCOME AND MEASURES: The primary end point was time from referral to treatment initiation among patients with advanced nonsquamous NSCLC using ctDNA testing before diagnosis (ACCELERATE [Accelerating Lung Cancer Diagnosis Through Liquid Biopsy] cohort). This cohort was compared with a reference cohort using standard tissue genotyping after tissue diagnosis. RESULTS: Of the 150 patients (median age at diagnosis, 68 years [range, 33-91 years]; 80 men [53%]) enrolled, 90 (60%) had advanced nonsquamous NSCLC. The median time to treatment was 39 days (IQR, 27-52 days) for the ACCELERATE cohort vs 62 days (IQR, 44-82 days) for the reference cohort (P < .001). Among the ACCELERATE cohort, the median turnaround time from sample collection to genotyping results was 7 days (IQR, 6-9 days) for plasma and 23 days (IQR, 18-28 days) for tissue NGS (P < .001). Of the 90 patients with advanced nonsquamous NSCLC, 21 (23%) started targeted therapy before tissue NGS results were available, and 11 (12%) had actionable alterations identified only through plasma testing. CONCLUSIONS AND RELEVANCE: This nonrandomized clinical trial found that the use of plasma ctDNA genotyping before tissue diagnosis among patients with suspected advanced NSCLC was associated with accelerated time to treatment compared with a reference cohort undergoing standard tissue testing. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04863924
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spelling pubmed-103699252023-07-27 Association of Circulating Tumor DNA Testing Before Tissue Diagnosis With Time to Treatment Among Patients With Suspected Advanced Lung Cancer: The ACCELERATE Nonrandomized Clinical Trial García-Pardo, Miguel Czarnecka-Kujawa, Kasia Law, Jennifer H. Salvarrey, Alexandra M. Fernandes, Roxanne Fan, Zhen J. Waddell, Thomas K. Yasufuku, Kazuhiro Liu, Geoffrey Donahoe, Laura L. Pierre, Andrew Le, Lisa W. Gunasegaran, Tharsiga Ghumman, Noor Shepherd, Frances A. Bradbury, Penelope A. Sacher, Adrian G. Schmid, Sabine Corke, Lucy Feng, Jamie Stockley, Tracy Pal, Prodipto Rogalla, Patrik Pipinikas, Christodoulos Howarth, Karen Ambasager, Bana Mezquita, Laura Tsao, Ming S. Leighl, Natasha B. JAMA Netw Open Original Investigation IMPORTANCE: Liquid biopsy has emerged as a complement to tumor tissue profiling for advanced non–small cell lung cancer (NSCLC). The optimal way to integrate liquid biopsy into the diagnostic algorithm for patients with newly diagnosed advanced NSCLC remains unclear. OBJECTIVE: To evaluate the use of circulating tumor DNA (ctDNA) genotyping before tissue diagnosis among patients with suspected advanced NSCLC and its association with time to treatment. DESIGN, SETTING, AND PARTICIPANTS: This single-group nonrandomized clinical trial was conducted among 150 patients at the Princess Margaret Cancer Centre–University Health Network (Toronto, Ontario, Canada) between July 1, 2021, and November 30, 2022. Patients referred for investigation and diagnosis of lung cancer were eligible if they had radiologic evidence of advanced lung cancer prior to a tissue diagnosis. INTERVENTIONS: Patients underwent plasma ctDNA testing with a next-generation sequencing (NGS) assay before lung cancer diagnosis. Diagnostic biopsy and tissue NGS were performed per standard of care. MAIN OUTCOME AND MEASURES: The primary end point was time from referral to treatment initiation among patients with advanced nonsquamous NSCLC using ctDNA testing before diagnosis (ACCELERATE [Accelerating Lung Cancer Diagnosis Through Liquid Biopsy] cohort). This cohort was compared with a reference cohort using standard tissue genotyping after tissue diagnosis. RESULTS: Of the 150 patients (median age at diagnosis, 68 years [range, 33-91 years]; 80 men [53%]) enrolled, 90 (60%) had advanced nonsquamous NSCLC. The median time to treatment was 39 days (IQR, 27-52 days) for the ACCELERATE cohort vs 62 days (IQR, 44-82 days) for the reference cohort (P < .001). Among the ACCELERATE cohort, the median turnaround time from sample collection to genotyping results was 7 days (IQR, 6-9 days) for plasma and 23 days (IQR, 18-28 days) for tissue NGS (P < .001). Of the 90 patients with advanced nonsquamous NSCLC, 21 (23%) started targeted therapy before tissue NGS results were available, and 11 (12%) had actionable alterations identified only through plasma testing. CONCLUSIONS AND RELEVANCE: This nonrandomized clinical trial found that the use of plasma ctDNA genotyping before tissue diagnosis among patients with suspected advanced NSCLC was associated with accelerated time to treatment compared with a reference cohort undergoing standard tissue testing. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04863924 American Medical Association 2023-07-25 /pmc/articles/PMC10369925/ /pubmed/37490292 http://dx.doi.org/10.1001/jamanetworkopen.2023.25332 Text en Copyright 2023 García-Pardo M et al. JAMA Network Open. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the CC-BY License.
spellingShingle Original Investigation
García-Pardo, Miguel
Czarnecka-Kujawa, Kasia
Law, Jennifer H.
Salvarrey, Alexandra M.
Fernandes, Roxanne
Fan, Zhen J.
Waddell, Thomas K.
Yasufuku, Kazuhiro
Liu, Geoffrey
Donahoe, Laura L.
Pierre, Andrew
Le, Lisa W.
Gunasegaran, Tharsiga
Ghumman, Noor
Shepherd, Frances A.
Bradbury, Penelope A.
Sacher, Adrian G.
Schmid, Sabine
Corke, Lucy
Feng, Jamie
Stockley, Tracy
Pal, Prodipto
Rogalla, Patrik
Pipinikas, Christodoulos
Howarth, Karen
Ambasager, Bana
Mezquita, Laura
Tsao, Ming S.
Leighl, Natasha B.
Association of Circulating Tumor DNA Testing Before Tissue Diagnosis With Time to Treatment Among Patients With Suspected Advanced Lung Cancer: The ACCELERATE Nonrandomized Clinical Trial
title Association of Circulating Tumor DNA Testing Before Tissue Diagnosis With Time to Treatment Among Patients With Suspected Advanced Lung Cancer: The ACCELERATE Nonrandomized Clinical Trial
title_full Association of Circulating Tumor DNA Testing Before Tissue Diagnosis With Time to Treatment Among Patients With Suspected Advanced Lung Cancer: The ACCELERATE Nonrandomized Clinical Trial
title_fullStr Association of Circulating Tumor DNA Testing Before Tissue Diagnosis With Time to Treatment Among Patients With Suspected Advanced Lung Cancer: The ACCELERATE Nonrandomized Clinical Trial
title_full_unstemmed Association of Circulating Tumor DNA Testing Before Tissue Diagnosis With Time to Treatment Among Patients With Suspected Advanced Lung Cancer: The ACCELERATE Nonrandomized Clinical Trial
title_short Association of Circulating Tumor DNA Testing Before Tissue Diagnosis With Time to Treatment Among Patients With Suspected Advanced Lung Cancer: The ACCELERATE Nonrandomized Clinical Trial
title_sort association of circulating tumor dna testing before tissue diagnosis with time to treatment among patients with suspected advanced lung cancer: the accelerate nonrandomized clinical trial
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10369925/
https://www.ncbi.nlm.nih.gov/pubmed/37490292
http://dx.doi.org/10.1001/jamanetworkopen.2023.25332
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