260MO - Liquid biopsy NGS test identifies actionable DNA mutations from CSF specimens of lung cancer patients

Background

Lung cancer is one of the top causes of cancer death. Liquid biopsies have emerged as a non-invasive method to identify patients who may respond to therapy, enabling dynamic monitoring of minimal residual disease and drug resistance. While plasma specimens have commonly been used for liquid biopsies, we validated the use of cerebrospinal fluid (CSF) for liquid biopsy next-generation sequencing (NGS) testing.

Methods

31 clinical CSF specimens from patients diagnosed with lung cancer were subjected to NGS testing in a CAP-accredited and CLIA-certified central laboratory using the using the LiquidHALLMARK® assay, a sensitive liquid biopsy NGS test.

Results

Actionable DNA mutations were detected in 77.4% (24/31) of CSF specimens. In 10 cases where CSF and matched plasma were available, the concordance of actionable mutations was 50% (5/10), with actionable mutations found only in CSF in four cases and actionable mutations found only in plasma in one case. Copy number variation (CNV) was detected in 35.5% (11/31) of cases. In five CNV-positive cases where matched plasma was available, CNVs were detected only in CSF and not in matched plasma. This is consistent with the observation by Wang et. al. that more genomic alterations such as CNVs can be detected in CSF than in plasma. Findings from cytology reports using CSF could be obtained in 10 cases (6 positive and 4 negative cases). The concordance between the presence of malignant cells by cytology and actionable variants by NGS was 90% (9/10), with an EGFR exon 19 deletion identified by NGS but no malignant cells detected by cytology in one case. In two further cases, cytology yielded inconclusive results, while NGS reported actionable findings.

Conclusions

These results demonstrate that NGS can sensitively detect the presence of tumor-associated DNA in CSF specimens from lung cancer patients, enabling detection of disease in the central nervous system such as leptomeningeal metastases.

Reference: Wang Y, Jiang F, Xia R, et al. Unique genomic alterations of cerebrospinal fluid cell-free DNA are critical for targeted therapy of non-small cell lung cancer with leptomeningeal metastasis. Front Oncol. Published online October 4, 2021.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Lucence Diagnostics Pte Ltd.

Funding

Lucence Diagnostics Pte Ltd.

Disclosure

M. Tan: Financial Interests, Personal and Institutional, Ownership Interest: Lucence. All other authors have declared no conflicts of interest.