Complementary Roles for Tissue- and Blood-Based Comprehensive Genomic Profiling for Detection of Actionable Driver Alterations in Advanced NSCLC
Introduction: Whereas tumor biopsy is the reference standard for genomic profiling of advanced NSCLC, there are now multiple assays approved by the Food and Drug Administration for liquid biopsy testing of circulating tumor DNA. Here, we study the incremental value that liquid biopsy comprehensive g...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-09-01
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| Series: | JTO Clinical and Research Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666364322001102 |
| _version_ | 1811271349303246848 |
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| author | Lee S. Schwartzberg, MD Gerald Li, PhD Khaled Tolba, MD Ariel B. Bourla, MD, PhD Katja Schulze, PhD Rujuta Gadgil, MS Alexander Fine, PhD Katherine T. Lofgren, PhD Ryon P. Graf, PhD Geoffrey R. Oxnard, MD Davey Daniel, MD |
| author_facet | Lee S. Schwartzberg, MD Gerald Li, PhD Khaled Tolba, MD Ariel B. Bourla, MD, PhD Katja Schulze, PhD Rujuta Gadgil, MS Alexander Fine, PhD Katherine T. Lofgren, PhD Ryon P. Graf, PhD Geoffrey R. Oxnard, MD Davey Daniel, MD |
| author_sort | Lee S. Schwartzberg, MD |
| collection | DOAJ |
| description | Introduction: Whereas tumor biopsy is the reference standard for genomic profiling of advanced NSCLC, there are now multiple assays approved by the Food and Drug Administration for liquid biopsy testing of circulating tumor DNA. Here, we study the incremental value that liquid biopsy comprehensive genomic profiling (CGP) adds to tissue molecular testing. Methods: Patients with metastatic NSCLC were enrolled in a prospective diagnostic study to receive circulating tumor DNA CGP; tissue CGP was optional in addition to their standard tissue testing. Focusing on nine genes listed per the National Comprehensive Cancer Network (NCCN) guidelines, liquid CGP was compared with available tissue testing results across three subcohorts: tissue CGP, standard-of-care testing of up to five biomarkers, or no tissue testing. Results: A total of 515 patients with advanced nonsquamous NSCLC received liquid CGP. Among 131 with tissue CGP results, NCCN biomarkers were detected in 86 (66%) with tissue CGP and 56 (43%) with liquid CGP (p < 0.001). Adding liquid CGP to tissue CGP detected no additional patients with NCCN biomarkers, whereas tissue CGP detected NCCN biomarkers in 30 patients (23%) missed by liquid CGP. Studying 264 patients receiving tissue testing of up to five genes, 102 (39%) had NCCN biomarkers detected in tissue, with an additional 48 (18%) detected using liquid CGP, including 18 with RET, MET, or ERBB2 drivers not studied in tissue. Conclusions: For the detection of patients with advanced nonsquamous NSCLC harboring 9 NCCN biomarkers, liquid CGP increases detection in patients with limited tissue results, but does not increase detection in patients with tissue CGP results available. In contrast, tissue CGP can add meaningfully to liquid CGP for detection of NCCN biomarkers and should be considered as a follow-up when an oncogenic driver is not identified by liquid biopsy. |
| first_indexed | 2024-04-12T22:18:33Z |
| format | Article |
| id | doaj.art-6ee120b19f7d45749c83a4e3900b99b2 |
| institution | Directory Open Access Journal |
| issn | 2666-3643 |
| language | English |
| last_indexed | 2024-04-12T22:18:33Z |
| publishDate | 2022-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JTO Clinical and Research Reports |
| spelling | doaj.art-6ee120b19f7d45749c83a4e3900b99b22022-12-22T03:14:26ZengElsevierJTO Clinical and Research Reports2666-36432022-09-0139100386Complementary Roles for Tissue- and Blood-Based Comprehensive Genomic Profiling for Detection of Actionable Driver Alterations in Advanced NSCLCLee S. Schwartzberg, MD0Gerald Li, PhD1Khaled Tolba, MD2Ariel B. Bourla, MD, PhD3Katja Schulze, PhD4Rujuta Gadgil, MS5Alexander Fine, PhD6Katherine T. Lofgren, PhD7Ryon P. Graf, PhD8Geoffrey R. Oxnard, MD9Davey Daniel, MD10West Cancer Center, Medical Director, Germantown, TennesseeFoundation Medicine, Clinical Development, Cambridge, MassachusettsFoundation Medicine, Clinical Development, Cambridge, MassachusettsFlatiron Health, Medical Director, New York, New YorkGenentech, Inc., Oncology Biomarker Development & Medical Affairs, South San Francisco, CaliforniaFoundation Medicine, Clinical Operations, Cambridge, MassachusettsFoundation Medicine, Cancer Genomics Research, Cambridge, MassachusettsFoundation Medicine, Decision Sciences, Cambridge, MassachusettsFoundation Medicine, Clinical Development, Cambridge, MassachusettsFoundation Medicine, Clinical Development, Cambridge, MassachusettsTennessee Oncology, Medical Oncology, Chattanooga, Tennessee; Corresponding author. Address for correspondence: Davey Daniel, MD, Tennessee Oncology, 605 Glenwood Drive, Suite 200, Chattanooga, TN.Introduction: Whereas tumor biopsy is the reference standard for genomic profiling of advanced NSCLC, there are now multiple assays approved by the Food and Drug Administration for liquid biopsy testing of circulating tumor DNA. Here, we study the incremental value that liquid biopsy comprehensive genomic profiling (CGP) adds to tissue molecular testing. Methods: Patients with metastatic NSCLC were enrolled in a prospective diagnostic study to receive circulating tumor DNA CGP; tissue CGP was optional in addition to their standard tissue testing. Focusing on nine genes listed per the National Comprehensive Cancer Network (NCCN) guidelines, liquid CGP was compared with available tissue testing results across three subcohorts: tissue CGP, standard-of-care testing of up to five biomarkers, or no tissue testing. Results: A total of 515 patients with advanced nonsquamous NSCLC received liquid CGP. Among 131 with tissue CGP results, NCCN biomarkers were detected in 86 (66%) with tissue CGP and 56 (43%) with liquid CGP (p < 0.001). Adding liquid CGP to tissue CGP detected no additional patients with NCCN biomarkers, whereas tissue CGP detected NCCN biomarkers in 30 patients (23%) missed by liquid CGP. Studying 264 patients receiving tissue testing of up to five genes, 102 (39%) had NCCN biomarkers detected in tissue, with an additional 48 (18%) detected using liquid CGP, including 18 with RET, MET, or ERBB2 drivers not studied in tissue. Conclusions: For the detection of patients with advanced nonsquamous NSCLC harboring 9 NCCN biomarkers, liquid CGP increases detection in patients with limited tissue results, but does not increase detection in patients with tissue CGP results available. In contrast, tissue CGP can add meaningfully to liquid CGP for detection of NCCN biomarkers and should be considered as a follow-up when an oncogenic driver is not identified by liquid biopsy.http://www.sciencedirect.com/science/article/pii/S2666364322001102Comprehensive genomic profilingLiquid biopsyBiomarkersTissue-based testingNSCLC |
| spellingShingle | Lee S. Schwartzberg, MD Gerald Li, PhD Khaled Tolba, MD Ariel B. Bourla, MD, PhD Katja Schulze, PhD Rujuta Gadgil, MS Alexander Fine, PhD Katherine T. Lofgren, PhD Ryon P. Graf, PhD Geoffrey R. Oxnard, MD Davey Daniel, MD Complementary Roles for Tissue- and Blood-Based Comprehensive Genomic Profiling for Detection of Actionable Driver Alterations in Advanced NSCLC JTO Clinical and Research Reports Comprehensive genomic profiling Liquid biopsy Biomarkers Tissue-based testing NSCLC |
| title | Complementary Roles for Tissue- and Blood-Based Comprehensive Genomic Profiling for Detection of Actionable Driver Alterations in Advanced NSCLC |
| title_full | Complementary Roles for Tissue- and Blood-Based Comprehensive Genomic Profiling for Detection of Actionable Driver Alterations in Advanced NSCLC |
| title_fullStr | Complementary Roles for Tissue- and Blood-Based Comprehensive Genomic Profiling for Detection of Actionable Driver Alterations in Advanced NSCLC |
| title_full_unstemmed | Complementary Roles for Tissue- and Blood-Based Comprehensive Genomic Profiling for Detection of Actionable Driver Alterations in Advanced NSCLC |
| title_short | Complementary Roles for Tissue- and Blood-Based Comprehensive Genomic Profiling for Detection of Actionable Driver Alterations in Advanced NSCLC |
| title_sort | complementary roles for tissue and blood based comprehensive genomic profiling for detection of actionable driver alterations in advanced nsclc |
| topic | Comprehensive genomic profiling Liquid biopsy Biomarkers Tissue-based testing NSCLC |
| url | http://www.sciencedirect.com/science/article/pii/S2666364322001102 |
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