Clinical Utility of Combined Tissue and Plasma Next-Generation Sequencing in Patients With Advanced, Treatment-Naïve NSCLC
Introduction: Tissue and plasma-based next-generation sequencing (NGS) have complementary roles in patients with advanced NSCLC. Nevertheless, whether there is any added clinical value in combining both methods in the treatment of naïve patients remains unclear. Methods: We retrospectively collected...
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Elsevier
2025-03-01
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| Series: | JTO Clinical and Research Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666364324001486 |
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| author | Helena Bote-de Cabo, MD Marco Siringo, MD Esther Conde, MD, PhD Susana Hernández, PhD Fernando López-Ríos, MD, PhD Alicia Castelo-Loureiro, MD Esther García-Lorenzo, MD Javier Baena, MD-PhD Mercedes Herrera, MD Ana Belén Enguita, MD Yolanda Ruano, PhD Jon Zugazagoitia, MD, PhD Luis Paz-Ares, MD, PhD |
| author_facet | Helena Bote-de Cabo, MD Marco Siringo, MD Esther Conde, MD, PhD Susana Hernández, PhD Fernando López-Ríos, MD, PhD Alicia Castelo-Loureiro, MD Esther García-Lorenzo, MD Javier Baena, MD-PhD Mercedes Herrera, MD Ana Belén Enguita, MD Yolanda Ruano, PhD Jon Zugazagoitia, MD, PhD Luis Paz-Ares, MD, PhD |
| author_sort | Helena Bote-de Cabo, MD |
| collection | DOAJ |
| description | Introduction: Tissue and plasma-based next-generation sequencing (NGS) have complementary roles in patients with advanced NSCLC. Nevertheless, whether there is any added clinical value in combining both methods in the treatment of naïve patients remains unclear. Methods: We retrospectively collected clinical and genomic data from 275 patients with treatment-naïve advanced NSCLC who had undergone plasma-based NGS at diagnosis in our institution. We analyzed patient data in two separate cohorts, each assessed with a different plasma-based NGS method: cohort 1 (n = 127, Guardant360), and cohort 2 (n = 148, FoundationACT/FoundationOne Liquid CDx). Ninety-five patients (75%) in cohort 1 and 108 patients (73%) in cohort 2 underwent concurrent amplicon-based tissue NGS testing locally. Results: Forty-three patients in cohort 1 (34%) and 49 patients in cohort 2 (33%) harbored European Society for Medical Oncology Scale for Clinical Actionability of Molecular Targets (ESCAT) I or II targetable driver alterations. The addition of orthogonal biopsy (tissue to liquid, or liquid to tissue) offered no relevant clinical value in cases with ESCAT I or II targetable drivers already detected by one method. In contrast, adding orthogonal biopsy incremented the detection of ESCAT I or II targetable drivers not only in cases with uninformative testing (undetectable circulating tumor DNA, unavailable/inadequate tissue) but also in about 5% of the patients with seemingly informative but driver undetected molecular results. The prevalence of ESCAT I or II targetable drivers in plasma was significantly higher in patients with adenocarcinoma, 20 pack-year or less smoking history, and abdominal metastases. Conclusions: Our study suggests that the addition of sequential orthogonal biopsy should be considered whenever an ESCAT I or II targetable driver has not been detected by the initial method, including cases with seemingly informative molecular analysis. |
| format | Article |
| id | doaj-art-9f0aed04ebe04e6580941b5c9d706e97 |
| institution | Kabale University |
| issn | 2666-3643 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
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| series | JTO Clinical and Research Reports |
| spelling | doaj-art-9f0aed04ebe04e6580941b5c9d706e972025-02-08T05:01:17ZengElsevierJTO Clinical and Research Reports2666-36432025-03-0163100778Clinical Utility of Combined Tissue and Plasma Next-Generation Sequencing in Patients With Advanced, Treatment-Naïve NSCLCHelena Bote-de Cabo, MD0Marco Siringo, MD1Esther Conde, MD, PhD2Susana Hernández, PhD3Fernando López-Ríos, MD, PhD4Alicia Castelo-Loureiro, MD5Esther García-Lorenzo, MD6Javier Baena, MD-PhD7Mercedes Herrera, MD8Ana Belén Enguita, MD9Yolanda Ruano, PhD10Jon Zugazagoitia, MD, PhD11Luis Paz-Ares, MD, PhD12Department of Medical Oncology, 12 de Octubre University Hospital, Madrid, Spain; Tumor Microenvironment and Immunotherapy Research Group, Instituto de Investigación del Hospital 12 de Octubre (i+12), Madrid, Spain; Lung Cancer Clinical Research Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain; Complutense University, Madrid, SpainDepartment of Medical Oncology, Sapienza University of Rome, ItalyComplutense University, Madrid, Spain; Department of Pathology, 12 de Octubre University Hospital, Madrid, Spain; Instituto de Investigación del Hospital 12 de Octubre (i+12), Madrid, Spain; CIBERONC, Instituto de Salud Carlos III, Madrid, SpainDepartment of Pathology, 12 de Octubre University Hospital, Madrid, Spain; Instituto de Investigación del Hospital 12 de Octubre (i+12), Madrid, SpainComplutense University, Madrid, Spain; Department of Pathology, 12 de Octubre University Hospital, Madrid, Spain; Instituto de Investigación del Hospital 12 de Octubre (i+12), Madrid, Spain; CIBERONC, Instituto de Salud Carlos III, Madrid, SpainDepartment of Medical Oncology, Fundación Jiménez Díaz University Hospital, Madrid, SpainSTART Madrid-FJD, Early Phase Clinical Trials Unit, Fundación Jiménez Díaz University Hospital, Madrid, SpainDepartment of Medical Oncology, 12 de Octubre University Hospital, Madrid, Spain; Tumor Microenvironment and Immunotherapy Research Group, Instituto de Investigación del Hospital 12 de Octubre (i+12), Madrid, Spain; Lung Cancer Clinical Research Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain; Complutense University, Madrid, SpainDepartment of Medical Oncology, 12 de Octubre University Hospital, Madrid, Spain; Tumor Microenvironment and Immunotherapy Research Group, Instituto de Investigación del Hospital 12 de Octubre (i+12), Madrid, Spain; Lung Cancer Clinical Research Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain; Complutense University, Madrid, SpainDepartment of Pathology, 12 de Octubre University Hospital, Madrid, SpainDepartment of Pathology, 12 de Octubre University Hospital, Madrid, SpainDepartment of Medical Oncology, 12 de Octubre University Hospital, Madrid, Spain; Tumor Microenvironment and Immunotherapy Research Group, Instituto de Investigación del Hospital 12 de Octubre (i+12), Madrid, Spain; Lung Cancer Clinical Research Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain; Complutense University, Madrid, Spain; CIBERONC, Instituto de Salud Carlos III, Madrid, Spain; Corresponding author. Address for correspondence: Jon Zugazagoitia, MD, PhD, Department of Medical Oncology, Hospital Universitario 12 de Octubre, Avenida de Córdoba s/n, 28041, Madrid, Spain.Department of Medical Oncology, 12 de Octubre University Hospital, Madrid, Spain; Lung Cancer Clinical Research Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain; Complutense University, Madrid, Spain; CIBERONC, Instituto de Salud Carlos III, Madrid, SpainIntroduction: Tissue and plasma-based next-generation sequencing (NGS) have complementary roles in patients with advanced NSCLC. Nevertheless, whether there is any added clinical value in combining both methods in the treatment of naïve patients remains unclear. Methods: We retrospectively collected clinical and genomic data from 275 patients with treatment-naïve advanced NSCLC who had undergone plasma-based NGS at diagnosis in our institution. We analyzed patient data in two separate cohorts, each assessed with a different plasma-based NGS method: cohort 1 (n = 127, Guardant360), and cohort 2 (n = 148, FoundationACT/FoundationOne Liquid CDx). Ninety-five patients (75%) in cohort 1 and 108 patients (73%) in cohort 2 underwent concurrent amplicon-based tissue NGS testing locally. Results: Forty-three patients in cohort 1 (34%) and 49 patients in cohort 2 (33%) harbored European Society for Medical Oncology Scale for Clinical Actionability of Molecular Targets (ESCAT) I or II targetable driver alterations. The addition of orthogonal biopsy (tissue to liquid, or liquid to tissue) offered no relevant clinical value in cases with ESCAT I or II targetable drivers already detected by one method. In contrast, adding orthogonal biopsy incremented the detection of ESCAT I or II targetable drivers not only in cases with uninformative testing (undetectable circulating tumor DNA, unavailable/inadequate tissue) but also in about 5% of the patients with seemingly informative but driver undetected molecular results. The prevalence of ESCAT I or II targetable drivers in plasma was significantly higher in patients with adenocarcinoma, 20 pack-year or less smoking history, and abdominal metastases. Conclusions: Our study suggests that the addition of sequential orthogonal biopsy should be considered whenever an ESCAT I or II targetable driver has not been detected by the initial method, including cases with seemingly informative molecular analysis.http://www.sciencedirect.com/science/article/pii/S2666364324001486Non-small cell lung cancerNext-generation sequencingLiquid biopsyTargetable driver alterations |
| spellingShingle | Helena Bote-de Cabo, MD Marco Siringo, MD Esther Conde, MD, PhD Susana Hernández, PhD Fernando López-Ríos, MD, PhD Alicia Castelo-Loureiro, MD Esther García-Lorenzo, MD Javier Baena, MD-PhD Mercedes Herrera, MD Ana Belén Enguita, MD Yolanda Ruano, PhD Jon Zugazagoitia, MD, PhD Luis Paz-Ares, MD, PhD Clinical Utility of Combined Tissue and Plasma Next-Generation Sequencing in Patients With Advanced, Treatment-Naïve NSCLC JTO Clinical and Research Reports Non-small cell lung cancer Next-generation sequencing Liquid biopsy Targetable driver alterations |
| title | Clinical Utility of Combined Tissue and Plasma Next-Generation Sequencing in Patients With Advanced, Treatment-Naïve NSCLC |
| title_full | Clinical Utility of Combined Tissue and Plasma Next-Generation Sequencing in Patients With Advanced, Treatment-Naïve NSCLC |
| title_fullStr | Clinical Utility of Combined Tissue and Plasma Next-Generation Sequencing in Patients With Advanced, Treatment-Naïve NSCLC |
| title_full_unstemmed | Clinical Utility of Combined Tissue and Plasma Next-Generation Sequencing in Patients With Advanced, Treatment-Naïve NSCLC |
| title_short | Clinical Utility of Combined Tissue and Plasma Next-Generation Sequencing in Patients With Advanced, Treatment-Naïve NSCLC |
| title_sort | clinical utility of combined tissue and plasma next generation sequencing in patients with advanced treatment naive nsclc |
| topic | Non-small cell lung cancer Next-generation sequencing Liquid biopsy Targetable driver alterations |
| url | http://www.sciencedirect.com/science/article/pii/S2666364324001486 |
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