Abstract
In the last decade, non–small-cell lung cancer (NSCLC) treatment has improved with
the approval of multiple therapies to target specific genetic alterations. Though,
next generation sequencing (NGS) has traditionally been conducted from tissue biopsy
samples, developing data supports the use of plasma-based circulating tumor DNA (ctDNA),
also known as “liquid biopsy,” to complement tissue biopsy approaches in guiding front-line
therapy. This study is a retrospective analysis of 170 new NSCLC patients treated
at 2 cancer centers within a 5-year period who received both tissue and liquid biopsy
NGS as standard of care. Based on a treatment schema defined by testing sufficiency,
biomarker detection, and turnaround time (TAT), physicians based the majority of their
treatments on liquid biopsy results (73.5%) versus tissue biopsy (25.9%). Liquid biopsy
NGS returned results on average 26.8 days faster than tissue and reported higher testing
success. For guideline-recommended biomarkers, liquid biopsy was 94.8% to 100% concordant
with tissue. In comparing testing modalities, a liquid-first approach identified guideline-recommended
biomarkers in 76.5% of patients versus 54.9% in a tissue-first approach. There was
no significant difference in time-to-treatment, or survival outcomes (overall survival
and progression free survival) based on liquid versus tissue biopsy findings. This
research demonstrates that liquid biopsy NGS is an effective tool to capture actionable
genetic alterations in NSCLC. Due to its high concordance to tissue, faster TAT, and
similarity in outcomes and time-to-treatment, liquid biopsy can be used either as
a first-line test or concordantly with tissue biopsy to guide treatment decisions
in NSCLC.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Clinical Lung CancerAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
Lung Cancer - Non-Small Cell - Statistics. Cancer.Net. https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/statistics. Published February 2022. Accessed May 24, 2022
- Next-generation sequencing informs diagnosis and identifies unexpected therapeutic targets in lung squamous cell carcinomas.Lung Cancer. 2020; 140: 35-41
- Targeted tissue and cell-free tumor DNA sequencing of advanced lung squamous-cell carcinoma reveals clinically significant prevalence of actionable alterations.Clin Lung Cancer. 2019; 20 (e3): 30-36
- Current and future applications of liquid biopsy in nonsmall cell lung cancer from early to advanced stages.Eur Respir Rev. 2020; 29190052
NCCN Guidelines. Non-small cell lung cancer. Version 3.2022. 2022.
- Somatic genomic testing in patients with metastatic or advanced cancer: ASCO provisional clinical opinion.J Clin Oncol. 2022; 40: 1231-1258https://doi.org/10.1200/JCO.21.02767
- Liquid biopsy for advanced NSCLC: a consensus statement from the international association for the study of lung cancer.J Thoracic Oncol. 2021; 16: 1647-1662https://doi.org/10.1016/j.jtho.2021.06.017
- Recommendations for the use of Next-Generation Sequencing (NGS) for patients with metastatic cancers: a report from the ESMO precision medicine working group.Ann Oncol. 2020; 31: 1491-1505https://doi.org/10.1016/j.annonc.2020.07.014
- Is tissue still the issue in detecting molecular alterations in lung cancer?.Respirology. 2020; 25: 933-943https://doi.org/10.1111/resp.13823
- Cons: can liquid biopsy replace tissue biopsy?-the US experience.Transl Lung Cancer Res. 2016; 5: 424-427
- Clinical relevance of blood-based CtDNA analysis: mutation detection and beyond.Br J Cancer. 2021; 124: 345-358https://doi.org/10.1038/s41416-020-01047-5
- Clinical utility of comprehensive cell-free DNA analysis to identify genomic biomarkers in patients with newly diagnosed metastatic non–small cell lung cancer.Clin Cancer Res. 2019; 25: 4691-4700
- Turnaround time of plasma next-generation sequencing in thoracic oncology patients: a quality improvement analysis.JCO Precision Oncol. 2020; : 1098-1108https://doi.org/10.1200/PO.20.00121
- Patients with advanced non–small cell lung cancer: are research biopsies a barrier to participation in clinical trials?.J Thoracic Oncol. 2016; 11: 79-84https://doi.org/10.1016/j.jtho.2015.09.006
- Non-small cell lung cancer clinical trials requiring biopsies with biomarker-specific results for enrollment provide unique challenges.Cancer. 2017; 123: 4800-4807https://doi.org/10.1002/cncr.31056
- Clinical implications of plasma-based genotyping with the delivery of personalized therapy in metastatic non–small cell lung cancer.JAMA Oncol. 2019; 5: 173-180https://doi.org/10.1001/jamaoncol.2018.4305
- Biomarker discovery and outcomes for comprehensive cell-free circulating tumor DNA versus standard-of-care tissue testing in advanced non–small-cell lung cancer.JCO Precision Oncol. 2021; : 93-102https://doi.org/10.1200/PO.20.00241
- Analytical and clinical validation of a digital sequencing panel for quantitative, highly accurate evaluation of cell-free circulating tumor DNA.PloS One. 2015; 10e0140712https://doi.org/10.1371/journal.pone.0140712
- The landscape of actionable genomic alterations in cell-free circulating tumor DNA from 21,807 advanced cancer patients.Clin Cancer Res: An Off J Am Assoc Cancer Res. 2018; 24: 3528-3538https://doi.org/10.1158/1078-0432.CCR-17-3837
- Validation of a plasma-based comprehensive cancer genotyping assay utilizing orthogonal tissue- and plasma-based methodologies.Clin Cancer Res: An Off J Am Assoc for Cancer Res. 2018; 24: 3539-3549https://doi.org/10.1158/1078-0432.CCR-17-3831
- Detection of therapeutically targetable driver and resistance mutations in lung cancer patients by next-generation sequencing of cell-free circulating tumor DNA.Clin Cancer Res: An Off J Am Assoc Cancer Res. 2016; 22: 5772-5782https://doi.org/10.1158/1078-0432.CCR-16-1231
- Genomic tissue analysis and liquid biopsy profiles from patients diagnosed with advanced adenocarcinoma of the lung.Clin Oncol. 2016; 1: 1099
- Success and failure rates of tumor genotyping techniques in routine pathological samples with non-small-cell lung cancer.Lung Cancer. 2014; 84: 39-44
- Clinical next-generation sequencing in patients with non-small cell lung cancer.Cancer. 2015; 121: 631-639
- Real-world utility of an amplicon-based next-generation sequencing liquid biopsy for broad molecular profiling in patients with advanced non-small-cell lung cancer.JCO Precis Oncol. 2019; 3 (eCollection 2019)https://doi.org/10.1200/PO.18.00211
- Outcomes in oncogenic-addicted advanced NSCLC patients with actionable mutations identified by liquid biopsy genomic profiling using a tagged amplicon-based NGS assay.PLoS ONE. 2020; 15e0234302
Article info
Publication history
Published online: November 25, 2022
Accepted:
November 19,
2022
Received in revised form:
November 16,
2022
Received:
July 26,
2022
Identification
Copyright
© 2022 Elsevier Inc. All rights reserved.
