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Article Abstract
Purpose: To evaluate the performance of a circulating tumor DNA (ctDNA) and circulating tumor RNA (ctRNA) liquid biopsy, LiquidHALLMARK (LHM), compared with tissue next-generation sequencing (NGS) and Guardant360 CDx (G360 ctDNA) liquid biopsy for biomarker detection in metastatic nonsquamous non-small cell lung cancer.
Patients And Methods: This multicenter, prospective study (ClinicalTrials.gov identifier: NCT04703153) enrolled patients across the United States and Singapore. Patients were tested with tissue NGS, LHM, and G360 ctDNA. The primary objective was noninferiority of LHM ctDNA to tissue NGS and G360 ctDNA. Secondary analyses included turnaround time (TAT), overall response rate (ORR), and progression-free survival (PFS), with exploratory analysis of the clinical utility of ctRNA.
Results: LHM ctDNA (48.2%) detected 11.4% fewer biomarker-positive patients than tissue NGS (59.6%) and did not meet noninferiority criteria. Compared with tissue NGS, LHM ctDNA and G360 ctDNA were concordant in 72.1% and 66.1% of patients, establishing noninferiority of LHM ctDNA to G360 ctDNA ( = .002). TAT was shorter for LHM ctDNA than for tissue NGS (mean 9.7 21.7 days; < .001). ORR/PFS was similar in patients receiving targeted therapy based on all three assays. Addition of ctRNA increased the diagnostic yield of tissue NGS-confirmed gene rearrangements by 28.6% relative to LHM ctDNA and all actionable biomarkers by 15.6% relative to G360 ctDNA. LHM ctDNA and ctRNA (51/68) detected 8.8% more biomarker-positive patients than G360 ctDNA (45/68), demonstrating superiority of LHM ctDNA and ctRNA ( = .001).
Conclusion: LHM ctDNA is noninferior to G360 ctDNA, but not tissue NGS. Treatment outcomes based on liquid biopsy are comparable with those based on tissue NGS. Incorporation of ctRNA into LHM ctDNA improves the diagnostic yield of actionable, tissue NGS-confirmed gene rearrangements.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203978 | PMC |
| http://dx.doi.org/10.1200/PO-25-00181 | DOI Listing |
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Purpose: To evaluate the performance of a circulating tumor DNA (ctDNA) and circulating tumor RNA (ctRNA) liquid biopsy, LiquidHALLMARK (LHM), compared with tissue next-generation sequencing (NGS) and Guardant360 CDx (G360 ctDNA) liquid biopsy for biomarker detection in metastatic nonsquamous non-small cell lung cancer.
Patients And Methods: This multicenter, prospective study (ClinicalTrials.gov identifier: NCT04703153) enrolled patients across the United States and Singapore.
Circulating Tumor DNA in Advanced EGFRex20+ NSCLC: Concordance with Tissue Biopsy, Monitoring of Response, and Resistance to High-Dose Osimertinib.
Target Oncol
July 2025
Department of Pulmonary Medicine, University of Groningen, University Medical Center Groningen, HPC AA11, Postbus 30.001, 9700RB, Groningen, The Netherlands.
Background: High-dose osimertinib shows modest anti-tumor activity and acceptable toxicity in patients with advanced non-small cell lung cancer (NSCLC) harboring an epidermal growth factor receptor exon 20 mutation (EGFRex20+). Plasma-derived circulating tumor DNA (ctDNA) is promising in monitoring responses and detecting resistance mechanisms to therapy.
Objective: We aimed to assess the concordance between variants detected in ctDNA to those found in corresponding tissue samples at baseline and progression, to analyze alterations in mutant ctDNA levels of EGFRex20+ variants as predictors of therapy response, and to identify resistance mechanisms to high-dose osimertinib as well as examine changes in mutant ctDNA levels of EGFRex20+ variants.