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Jamie Mong
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P34 - Pathology - Liquid Biopsy (ID 104)
- Event: WCLC 2020
- Type: Posters
- Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P34.03 - A ‘Plasma-First’ Molecular Profiling Approach Complements Actionable Mutation Detection in Suspected Lung Cancer Patients (ID 2133)
00:00 - 00:00 | Presenting Author(s): Jamie Mong
- Abstract
Introduction
Tissue biopsy and associated molecular profiling is an integral part of the diagnostic approach to suspected lung cancer. It is however invasive, slow and associated with limitations of tissue heterogeneity. The ‘plasma-first’ paradigm of liquid biopsy may complement diagnosis in providing additional information and may be particularly helpful in patients from whom obtaining tissue is challenging.
Methods
Patients with suspected lung cancer (n=71, median age=65) were recruited prospectively between 2013-2015 at the Department of Respiratory Medicine, Changi General Hospital, Singapore. Blood was collected first, followed by baseline tissue sampling by bronchoscopy or effusion collection within 48 hrs. Matched plasma cfDNA testing on 1 to 9 mL plasma was done using an ultrasensitive amplicon-based next-generation sequencing (NGS) panel including EGFR, BRAF, KRAS, ERBB2 and MET genes. Targeted EGFR diagnostic testing for lung cancer was done in a CAP-accredited clinical laboratory. Additional tissue biopsy molecular profiling was done with the same NGS panel for a subset of 36 patients. Concordance between methods and sample types were assessed. This study is registered under NCT04254497.
Results
Among confirmed NSCLC cases (n = 54), diagnostic molecular EGFR test results were available for 38 patients. Of the 16 NSCLC cases without EGFR test results, 10 were biopsied but informative results could not be obtained. Two patients above 80 years of age were not biopsied and remaining 4 passed away within 1 to 4 weeks of initial diagnosis by cytology or histology. Plasma testing was successful in 100% of patients versus 70.4% by routine diagnostic testing. Of the NSCLC cases with routine EGFR tissue test results, 38% (13/38) were positive for EGFR sensitizing mutations. Compared to standard testing, overall sensitivity of EGFR detection by plasma NGS testing was 77% (10/13) and specificity was 100% (25/25). Among EGFR-negative cases, plasma NGS testing identified additional actionable mutations in 7 cases, including KRAS G12D, MET exon 14 skipping, BRAF V600E, EGFR exon 20 insertion mutations. This amounted to an additional diagnostic yield of 28% (7/25) by plasma testing of NSCLC cases. The finding of additional actionable mutations was verified by the concomitant testing of tissue/pleural effusion samples with the same NGS panel for 5 cases. Two of 16 cases lacking standard EGFR testing results, were positive for EGFR mutations by NGS in both plasma and tissue. Cases with no EGFR mutations also harbored non-targetable mutations in nearly half (12 of 25 = 48%) of cases. Overall, the concordance of actionable mutations observed between plasma and tumor testing by NGS for NSCLC cases (n = 30) was 91.7%. Among cases confirmed to be not cancer (n = 9), only one case harboured a tissue and plasma-matched ALK frameshift mutation of unknown significance and all other cases had no mutations detected in both plasma and tissue.
Conclusion
A high concordance of actionable mutations between NSCLC tissue and plasma was observed in the first-line setting. Additional actionable mutations were observed using plasma, underlining the potential of the ‘plasma-first’ approach for complementing the comprehensive diagnostic profiling of lung cancer patients.
