Liquid biopsy as an option for predictive testing and prognosis in patients with lung cancer

Abstract

Background The aim of this study was to investigate the clinical value of liquid biopsy as a primary source for variant analysis in lung cancer. In addition, we sought to characterize liquid biopsy variants and to correlate mutational load to clinical data. Methods Circulating cell-free DNA was extracted from plasma from patients with lung cancer (n = 60) and controls with benign lung disease (n = 16). Variant analysis was performed using the AVENIO ctDNA Surveillance kit and the results were correlated to clinical and variant analysis data from tumor tissue or cytology retrieved from clinical routine diagnostics. Results There were significantly more variants detected in lung cancer cases compared to controls (p = 0.011), but no difference between the histological subgroups of lung cancer was found (p = 0.465). Furthermore, significantly more variants were detected in patients with stage IIIb–IV disease compared to patients with stage I–IIIa (median 7 vs 4, p = 0.017). Plasma cfDNA mutational load was significantly associated with overall survival (p = 0.010). The association persisted when adjusted for stage and ECOG performance status (HR: 3.64, 95% CI 1.37–9.67, p = 0.009). Agreement between tumor and plasma samples significantly differed with stage; patients with stage IIIb–IV disease showed agreement in 88.2% of the cases with clinically relevant variants, compared to zero cases in stage I–IIIa (p = 0.004). Furthermore, one variant in EGFR, two in KRAS, and one in BRAF were detected in plasma but not in tumor samples. Conclusion This study concludes that in the vast majority of advanced NSCLC patients a reliable variant analysis can be performed using liquid biopsy from plasma. Furthermore, we found that the number of variants in plasma is associated with prognosis, possibly indicating a strategy for closer follow up on this crucial patient group.

NTRK Fusion in Non-Small Cell Lung Cancer: Diagnosis, Therapy, and TRK Inhibitor Resistance

“…For example, Oncomine Comprehensive Assay by Thermo Fisher and The TruSight Oncology 500 assay by Illumina are hybrid panels including all three NTRK genes ( 56 , 57 ). Currently, a number of NGS panels based on DNA or RNA are designed for liquid biopsy when no sufficient tumor tissue specimen is available, such as Guardant360 panel ( 58 ) and AVENIO Extended ctDNA Analysis Kits ( 59 ). However, the sensitivity of such methods still requires future improvement.…”

Liquid biopsy in non-small cell lung cancer: a meta-analysis of state-of-the-art and future perspectives

“…Literature search generated 517 papers: after reading the titles, abstracts and full-text, 17 articles were included in the meta-analysis ( Rachiglio et al, 2016 ; He et al, 2017 ; Yang et al, 2017 ; Guo et al, 2018 ; Ito K et al, 2018 ; Wan et al, 2018 ; Ding et al, 2019 ; Li et al, 2019 ; Papadopoulou et al, 2019 ; Schrock et al, 2019 ; Lin et al, 2021 ; Park et al, 2021 ; Qvick et al, 2021 ; Satapathy et al, 2021 ; Batra et al, 2022 ; Ito M et al, 2022 ; Prabhash et al, 2022 ), summing up to a total of 1711 patients. Figure 1 represents the flowchart of the selection process, following PRISMA guidelines [PRISMA ( prisma-statement.org )].…”

Detection of KRAS mutation using plasma samples in non-small-cell lung cancer: a systematic review and meta-analysis

“…AVENIO ctDNA Surveillance kit (Roche) is also a commercial panel using hybridization-based target enrichment. A study using AVENIO ctDNA Surveillance kit showed sensitivity of 72.73%, specificity of 100%, and concordance rate of 94.23% ( 41 ).…”