Genomic Landscape of NSCLC in the Republic of Ireland
Introduction: The identification of genomic “targets” through next-generation sequencing (NGS) of patient’s NSCLC tumors has resulted in a rapid expansion of targeted treatment options for selected patients. This retrospective study aims to identify the proportion of patients with advanced NSCLC in...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-02-01
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| Series: | JTO Clinical and Research Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666364323001704 |
| _version_ | 1797292900469440512 |
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| author | Rachel J. Keogh, MB BCH BAO Martin P. Barr, PhD Anna Keogh, MB BCH BAO David McMahon, MB BCH BAO Cathal O’Brien, PhD Stephen P. Finn, MD Jarushka Naidoo, MBBCH, MHS |
| author_facet | Rachel J. Keogh, MB BCH BAO Martin P. Barr, PhD Anna Keogh, MB BCH BAO David McMahon, MB BCH BAO Cathal O’Brien, PhD Stephen P. Finn, MD Jarushka Naidoo, MBBCH, MHS |
| author_sort | Rachel J. Keogh, MB BCH BAO |
| collection | DOAJ |
| description | Introduction: The identification of genomic “targets” through next-generation sequencing (NGS) of patient’s NSCLC tumors has resulted in a rapid expansion of targeted treatment options for selected patients. This retrospective study aims to identify the proportion of patients with advanced NSCLC in the Republic of Ireland whose tumors harbor actionable genomic alterations through broad NGS panel testing. Methods: Institutional review board approval was obtained before study initiation. Patients with NSCLC whose tumors underwent genomic testing through the largest available NGS panel at a nationally funded Cancer Molecular Diagnostics laboratory (St. James’s Hospital) between June 2017 and June 2022 were identified. Patient demographics and tumor-related data were collected by retrospective review from all cancer centers in Ireland, referring to the Cancer Molecular Diagnostics laboratory. A total of 203 (9%) tumor samples were excluded due to insufficient neoplastic cell content. Genomic data were collected through retrospective search of Ion Reporter software. The spectrum and proportion of patients with oncogenic driver mutations were evaluated using descriptive statistics (SPSS version 29.0). Results: In total, 2052 patients were identified. Patients were referred from 23 different hospital sites and all four geographic regions (Leinster = 1091, 53%; Munster = 763, 37.2%; Connacht = 191, 9.3%; Ulster = 7, 0.3%). Median age was 69 (range: 26–94) years; 53% were male. The most common tumor histologic subtype was adenocarcinoma (77%, n = 1577). An actionable genomic alteration was identified in 1099 cases (53%), the most common of which was KRAS (n = 657, 32%). Less frequently, NSCLC tumors harbored the following: MET exon 14 skipping (n = 53, 2.6%), MET amplification (n = 26, 1.3%), EGFR (n = 181, 8.8%), HER2 (n = 35, 1.7%), and BRAF (n = 72, 3.5%) mutations. Fusions were detected in 76 patients (3.7%) including ALK (n = 44, 58%), RET (n = 11, 14.5%), ROS1 (n = 16, 21%), and FGFR3 (n = 5, 6.6%), whereas no NTRK fusion was identified. Co-alterations were detected in 114 patients (5.6%), the most common of which was KRAS/PIK3CA (n = 19, 17%), EGFR/PIK3CA (n = 10, 8.5%), and KRAS/IDH1 (n = 9, 8%). Other co-alterations of interest identified included KRAS G12A/ROS1 fusion (n = 1) and KRAS G12C/BRAF G469A (n = 2). Conclusions: This is the first retrospective study to comprehensively characterize the genomic landscape of NSCLC in Ireland, using the broadest available NGS panel. Actionable alterations were identified in 53.4% of the patients, and KRAS was the most common oncogenic driver alteration. Our study revealed a lower prevalence of patients whose tumor harbors ALK, ROS1, and RET fusions, compared with similar data sets. |
| first_indexed | 2024-03-07T20:04:10Z |
| format | Article |
| id | doaj.art-7485f09829ab430c9cdf25af69656df9 |
| institution | Directory Open Access Journal |
| issn | 2666-3643 |
| language | English |
| last_indexed | 2024-03-07T20:04:10Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JTO Clinical and Research Reports |
| spelling | doaj.art-7485f09829ab430c9cdf25af69656df92024-02-28T05:14:13ZengElsevierJTO Clinical and Research Reports2666-36432024-02-0152100627Genomic Landscape of NSCLC in the Republic of IrelandRachel J. Keogh, MB BCH BAO0Martin P. Barr, PhD1Anna Keogh, MB BCH BAO2David McMahon, MB BCH BAO3Cathal O’Brien, PhD4Stephen P. Finn, MD5Jarushka Naidoo, MBBCH, MHS6Department of Medical Oncology, Beaumont RCSI Cancer Centre, Dublin, IrelandThoracic Oncology Research Group, Trinity St James’s Cancer Institute, St James’s Hospital, Dublin, Ireland; School of Medicine, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, IrelandSchool of Medicine, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland; Department of Histopathology, St James’s Hospital, Dublin, IrelandDepartment Medical Oncology, St James’s Hospital, Dublin, IrelandCancer Molecular Diagnostics Laboratory, St James’s Hospital, Dublin, IrelandThoracic Oncology Research Group, Trinity St James’s Cancer Institute, St James’s Hospital, Dublin, Ireland; School of Medicine, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland; Department of Histopathology, St James’s Hospital, Dublin, Ireland; Cancer Molecular Diagnostics Laboratory, St James’s Hospital, Dublin, IrelandDepartment of Medical Oncology, Beaumont RCSI Cancer Centre, Dublin, Ireland; Beaumont Hospital, Dublin, Ireland; RCSI University of Health Sciences, Dublin, Ireland; Sidney Kimmel Comprehensive Cancer Centre at Johns Hopkins University, Baltimore, Maryland; Corresponding author. Address for correspondence: Jarushka Naidoo, MBBCH MHS, Research and Education Centre at Beaumont Hospital, RCSI University of Health Sciences, Beaumont Road, Dublin 9, Ireland.Introduction: The identification of genomic “targets” through next-generation sequencing (NGS) of patient’s NSCLC tumors has resulted in a rapid expansion of targeted treatment options for selected patients. This retrospective study aims to identify the proportion of patients with advanced NSCLC in the Republic of Ireland whose tumors harbor actionable genomic alterations through broad NGS panel testing. Methods: Institutional review board approval was obtained before study initiation. Patients with NSCLC whose tumors underwent genomic testing through the largest available NGS panel at a nationally funded Cancer Molecular Diagnostics laboratory (St. James’s Hospital) between June 2017 and June 2022 were identified. Patient demographics and tumor-related data were collected by retrospective review from all cancer centers in Ireland, referring to the Cancer Molecular Diagnostics laboratory. A total of 203 (9%) tumor samples were excluded due to insufficient neoplastic cell content. Genomic data were collected through retrospective search of Ion Reporter software. The spectrum and proportion of patients with oncogenic driver mutations were evaluated using descriptive statistics (SPSS version 29.0). Results: In total, 2052 patients were identified. Patients were referred from 23 different hospital sites and all four geographic regions (Leinster = 1091, 53%; Munster = 763, 37.2%; Connacht = 191, 9.3%; Ulster = 7, 0.3%). Median age was 69 (range: 26–94) years; 53% were male. The most common tumor histologic subtype was adenocarcinoma (77%, n = 1577). An actionable genomic alteration was identified in 1099 cases (53%), the most common of which was KRAS (n = 657, 32%). Less frequently, NSCLC tumors harbored the following: MET exon 14 skipping (n = 53, 2.6%), MET amplification (n = 26, 1.3%), EGFR (n = 181, 8.8%), HER2 (n = 35, 1.7%), and BRAF (n = 72, 3.5%) mutations. Fusions were detected in 76 patients (3.7%) including ALK (n = 44, 58%), RET (n = 11, 14.5%), ROS1 (n = 16, 21%), and FGFR3 (n = 5, 6.6%), whereas no NTRK fusion was identified. Co-alterations were detected in 114 patients (5.6%), the most common of which was KRAS/PIK3CA (n = 19, 17%), EGFR/PIK3CA (n = 10, 8.5%), and KRAS/IDH1 (n = 9, 8%). Other co-alterations of interest identified included KRAS G12A/ROS1 fusion (n = 1) and KRAS G12C/BRAF G469A (n = 2). Conclusions: This is the first retrospective study to comprehensively characterize the genomic landscape of NSCLC in Ireland, using the broadest available NGS panel. Actionable alterations were identified in 53.4% of the patients, and KRAS was the most common oncogenic driver alteration. Our study revealed a lower prevalence of patients whose tumor harbors ALK, ROS1, and RET fusions, compared with similar data sets.http://www.sciencedirect.com/science/article/pii/S2666364323001704Non–small cell lung cancerBiomarkersGenomic landscapeIreland |
| spellingShingle | Rachel J. Keogh, MB BCH BAO Martin P. Barr, PhD Anna Keogh, MB BCH BAO David McMahon, MB BCH BAO Cathal O’Brien, PhD Stephen P. Finn, MD Jarushka Naidoo, MBBCH, MHS Genomic Landscape of NSCLC in the Republic of Ireland JTO Clinical and Research Reports Non–small cell lung cancer Biomarkers Genomic landscape Ireland |
| title | Genomic Landscape of NSCLC in the Republic of Ireland |
| title_full | Genomic Landscape of NSCLC in the Republic of Ireland |
| title_fullStr | Genomic Landscape of NSCLC in the Republic of Ireland |
| title_full_unstemmed | Genomic Landscape of NSCLC in the Republic of Ireland |
| title_short | Genomic Landscape of NSCLC in the Republic of Ireland |
| title_sort | genomic landscape of nsclc in the republic of ireland |
| topic | Non–small cell lung cancer Biomarkers Genomic landscape Ireland |
| url | http://www.sciencedirect.com/science/article/pii/S2666364323001704 |
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