Complementing Tissue Testing With Plasma Mutation Profiling Improves Therapeutic Decision-Making for Patients With Lung Cancer
BackgroundTissue biopsy is an integral part of the diagnostic approach to lung cancer. It is however invasive and limited by heterogeneity. Liquid biopsies may complement tissue testing by providing additional molecular information and may be particularly helpful in patients from whom obtaining suff...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-02-01
|
| Series: | Frontiers in Medicine |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2022.758464/full |
| _version_ | 1818897265031380992 |
|---|---|
| author | Yukti Choudhury Min-Han Tan Jun Li Shi Augustine Tee Kao Chin Ngeow Jonathan Poh Ruth Rosalyn Goh Ruth Rosalyn Goh Jamie Mong |
| author_facet | Yukti Choudhury Min-Han Tan Jun Li Shi Augustine Tee Kao Chin Ngeow Jonathan Poh Ruth Rosalyn Goh Ruth Rosalyn Goh Jamie Mong |
| author_sort | Yukti Choudhury |
| collection | DOAJ |
| description | BackgroundTissue biopsy is an integral part of the diagnostic approach to lung cancer. It is however invasive and limited by heterogeneity. Liquid biopsies may complement tissue testing by providing additional molecular information and may be particularly helpful in patients from whom obtaining sufficient tissue for genomic profiling is challenging.MethodsPatients with suspected lung cancer (n = 71) were prospectively recruited. Blood and diagnostic tissue samples were collected within 48 h of each other. Plasma cell-free DNA (cfDNA) testing was done using an ultrasensitive amplicon-based next-generation sequencing (NGS) panel (plasma NGS testing). For cases diagnosed as non-small cell lung carcinoma (NSCLC) via histology or cytology, targeted testing for epidermal growth factor receptor (EGFR) mutations was performed using tissue biopsy samples (tissue EGFR testing), where available. Concordance of clinically actionable mutations between methods and sample types was assessed.ResultsFor confirmed NSCLC cases (n = 54), tissue EGFR test results were available only for 70.3% (38/54) due to sample inadequacies, compared to blood samples for 98.1% (53/54) cases. Tissue EGFR testing identified sensitizing EGFR (L858R or exon 19 deletion) mutation in 31.6% (12/38) of cases. Plasma NGS identified clinically actionable mutations in 37.7% (20/53) of cases, including EGFR mutations in two cases with no tissue EGFR results, and mutations in KRAS, BRAF, and MET. The overall sensitivity of sensitizing EGFR mutation detection by plasma NGS was 75% (9/12), and specificity was 100% (25/25) in patients tested in both tissue EGFR and plasma NGS (n = 37). In this cohort of patients, tissue EGFR testing alone informed clinical decisions in 22.2% (12/54) of cases. Adding plasma NGS to tissue EGFR testing increased the detection rate of actionable mutations to 42.6% (23/54), representing a 1.9-fold increase in clinically relevant findings. The average turnaround time of plasma NGS was shorter than standard tissue testing (10 vs. 29.9 days, p < 0.05).ConclusionsIn the first-line setting, plasma NGS was highly concordant with tissue EGFR testing. Plasma NGS increases the detection of actionable findings with a shorter time to results. This study outlines the clinical utility of complementary plasma mutation profiling in the routine management of lung cancer patients. |
| first_indexed | 2024-12-19T19:13:25Z |
| format | Article |
| id | doaj.art-18bc92e5fa164925bad8db8ad4d66c9f |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-12-19T19:13:25Z |
| publishDate | 2022-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-18bc92e5fa164925bad8db8ad4d66c9f2022-12-21T20:09:12ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2022-02-01910.3389/fmed.2022.758464758464Complementing Tissue Testing With Plasma Mutation Profiling Improves Therapeutic Decision-Making for Patients With Lung CancerYukti Choudhury0Min-Han Tan1Jun Li Shi2Augustine Tee3Kao Chin Ngeow4Jonathan Poh5Ruth Rosalyn Goh6Ruth Rosalyn Goh7Jamie Mong8Lucence Diagnostics Pte. Ltd., Singapore, SingaporeLucence Health Inc, Palo Alto, CA, United StatesInstitute of Bioengineering and Nanotechnology, Singapore, SingaporeDepartment of Respiratory and Critical Care Medicine, Changi General Hospital, Singapore, SingaporeLucence Diagnostics Pte. Ltd., Singapore, SingaporeLucence Diagnostics Pte. Ltd., Singapore, SingaporeLucence Diagnostics Pte. Ltd., Singapore, SingaporeFaculty of Medicine, Imperial College London, London, United KingdomInstitute of Bioengineering and Bioimaging, Singapore, SingaporeBackgroundTissue biopsy is an integral part of the diagnostic approach to lung cancer. It is however invasive and limited by heterogeneity. Liquid biopsies may complement tissue testing by providing additional molecular information and may be particularly helpful in patients from whom obtaining sufficient tissue for genomic profiling is challenging.MethodsPatients with suspected lung cancer (n = 71) were prospectively recruited. Blood and diagnostic tissue samples were collected within 48 h of each other. Plasma cell-free DNA (cfDNA) testing was done using an ultrasensitive amplicon-based next-generation sequencing (NGS) panel (plasma NGS testing). For cases diagnosed as non-small cell lung carcinoma (NSCLC) via histology or cytology, targeted testing for epidermal growth factor receptor (EGFR) mutations was performed using tissue biopsy samples (tissue EGFR testing), where available. Concordance of clinically actionable mutations between methods and sample types was assessed.ResultsFor confirmed NSCLC cases (n = 54), tissue EGFR test results were available only for 70.3% (38/54) due to sample inadequacies, compared to blood samples for 98.1% (53/54) cases. Tissue EGFR testing identified sensitizing EGFR (L858R or exon 19 deletion) mutation in 31.6% (12/38) of cases. Plasma NGS identified clinically actionable mutations in 37.7% (20/53) of cases, including EGFR mutations in two cases with no tissue EGFR results, and mutations in KRAS, BRAF, and MET. The overall sensitivity of sensitizing EGFR mutation detection by plasma NGS was 75% (9/12), and specificity was 100% (25/25) in patients tested in both tissue EGFR and plasma NGS (n = 37). In this cohort of patients, tissue EGFR testing alone informed clinical decisions in 22.2% (12/54) of cases. Adding plasma NGS to tissue EGFR testing increased the detection rate of actionable mutations to 42.6% (23/54), representing a 1.9-fold increase in clinically relevant findings. The average turnaround time of plasma NGS was shorter than standard tissue testing (10 vs. 29.9 days, p < 0.05).ConclusionsIn the first-line setting, plasma NGS was highly concordant with tissue EGFR testing. Plasma NGS increases the detection of actionable findings with a shorter time to results. This study outlines the clinical utility of complementary plasma mutation profiling in the routine management of lung cancer patients.https://www.frontiersin.org/articles/10.3389/fmed.2022.758464/fullliquid biopsy and circulating tumor DNAnon-small cell lung cancer (NSCLC)plasma-firstnext generation sequencingamplicon-based NGStumor heterogeneity |
| spellingShingle | Yukti Choudhury Min-Han Tan Jun Li Shi Augustine Tee Kao Chin Ngeow Jonathan Poh Ruth Rosalyn Goh Ruth Rosalyn Goh Jamie Mong Complementing Tissue Testing With Plasma Mutation Profiling Improves Therapeutic Decision-Making for Patients With Lung Cancer Frontiers in Medicine liquid biopsy and circulating tumor DNA non-small cell lung cancer (NSCLC) plasma-first next generation sequencing amplicon-based NGS tumor heterogeneity |
| title | Complementing Tissue Testing With Plasma Mutation Profiling Improves Therapeutic Decision-Making for Patients With Lung Cancer |
| title_full | Complementing Tissue Testing With Plasma Mutation Profiling Improves Therapeutic Decision-Making for Patients With Lung Cancer |
| title_fullStr | Complementing Tissue Testing With Plasma Mutation Profiling Improves Therapeutic Decision-Making for Patients With Lung Cancer |
| title_full_unstemmed | Complementing Tissue Testing With Plasma Mutation Profiling Improves Therapeutic Decision-Making for Patients With Lung Cancer |
| title_short | Complementing Tissue Testing With Plasma Mutation Profiling Improves Therapeutic Decision-Making for Patients With Lung Cancer |
| title_sort | complementing tissue testing with plasma mutation profiling improves therapeutic decision making for patients with lung cancer |
| topic | liquid biopsy and circulating tumor DNA non-small cell lung cancer (NSCLC) plasma-first next generation sequencing amplicon-based NGS tumor heterogeneity |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2022.758464/full |
| work_keys_str_mv | AT yuktichoudhury complementingtissuetestingwithplasmamutationprofilingimprovestherapeuticdecisionmakingforpatientswithlungcancer AT minhantan complementingtissuetestingwithplasmamutationprofilingimprovestherapeuticdecisionmakingforpatientswithlungcancer AT junlishi complementingtissuetestingwithplasmamutationprofilingimprovestherapeuticdecisionmakingforpatientswithlungcancer AT augustinetee complementingtissuetestingwithplasmamutationprofilingimprovestherapeuticdecisionmakingforpatientswithlungcancer AT kaochinngeow complementingtissuetestingwithplasmamutationprofilingimprovestherapeuticdecisionmakingforpatientswithlungcancer AT jonathanpoh complementingtissuetestingwithplasmamutationprofilingimprovestherapeuticdecisionmakingforpatientswithlungcancer AT ruthrosalyngoh complementingtissuetestingwithplasmamutationprofilingimprovestherapeuticdecisionmakingforpatientswithlungcancer AT ruthrosalyngoh complementingtissuetestingwithplasmamutationprofilingimprovestherapeuticdecisionmakingforpatientswithlungcancer AT jamiemong complementingtissuetestingwithplasmamutationprofilingimprovestherapeuticdecisionmakingforpatientswithlungcancer |