Up-front cell-free DNA next generation sequencing improves target identification in UK first line advanced non-small cell lung cancer (NSCLC) patients.
Date
2022-08-01ICR Author
Author
Cui, W
Milner-Watts, C
O'Sullivan, H
Lyons, H
Minchom, A
Bhosle, J
Davidson, M
Yousaf, N
Scott, S
Faull, I
Kushnir, M
Nagy, R
O'Brien, M
Popat, S
Type
Journal Article
Metadata
Show full item recordAbstract
BACKGROUND: Genomic sequencing is necessary for first-line advanced non-small cell lung cancer (aNSCLC) treatment decision-making. Tissue next generation sequencing (NGS) is standard but tissue quantity, quality, and time-to-results remains problematic. Here, we compare upfront cell-free-DNA (cfDNA) NGS clinical utility against routine tissue testing in patients with aNSCLC. METHODS: cfDNA-NGS was performed in consecutive, newly identified aNSCLC patients between December 2019-October 2021 alongside routine tissue genotyping. Variants were interpreted using AMP/ASCO/CAP guidelines. The primary endpoint was tier-1 variants detected on cfDNA-NGS. cfDNA-NGS results were compared to tissue results. RESULTS: Of 311 patients, 282 (91%) had an informative cfDNA-NGS test; 118 (38%) patients had a tier-1 variant identified by cfDNA-NGS. Of 243 patients with paired tissue-cfDNA tests, 122 (50%) tissue tests were informative; 85 (35%) tissue tests identified a tier-1 variant. cfDNA-NGS detected 39 additional tier-1 variants compared to tissue alone, increasing the tier-1 detection rate by 46% (from 85 to 124). The sensitivity of cfDNA-NGS relative to tissue was 75% (25% tissue tier-1 variants were not detected on cfDNA-NGS); 33% of cfDNA tier-1 variants were not identified on tissue tests. Median time from request-to-report was shorter for cfDNA-NGS versus tissue (8 versus 22 days; p < 0.0001). A total of 245 (79%) patients received first-line systemic-therapy: 49 (20%) with cfDNA-NGS results alone. Median time from sampling-to-commencement of first-line treatment was shorter for cfDNA-NGS blood draw versus first tissue biopsy (16 versus 35 days; p < 0.0001). CONCLUSIONS: cfDNA-NGS increased the tier-1 variant detection rate with high concordance with tissue, and halves time-to-treatment. 'Plasma-first' upfront cfDNA-NGS use should be considered routinely for aNSCLC.
Collections
Subject
Circulating tumour DNA
Genomic sequencing
Lung cancer
Non-small cell lung cancer
Targeted therapy
Carcinoma, Non-Small-Cell Lung
Cell-Free Nucleic Acids
High-Throughput Nucleotide Sequencing
Humans
Lung Neoplasms
Mutation
United Kingdom
Research team
Adult DDU ICR & RM
Language
eng
Date accepted
2022-05-10
License start date
2022-08-01
Citation
European Journal of Cancer, 2022, 171 pp. 44 - 54
Publisher
ELSEVIER SCI LTD