CSF Liquid Biopsy Shows High Impact in CNS Lymphoma Diagnosis & Monitoring

CSF Liquid Biopsy Shows Promise in Diagnosing and Monitoring CNS Lymphoma

A recent retrospective study published in Lymphatics demonstrates that a cerebrospinal fluid (CSF) liquid biopsy, utilizing the Summit™ and Vantage™ tests from Belay Diagnostics, provides clinically meaningful impact in 82% of central nervous system lymphoma (CNSL) cases.

The study, which analyzed 50 CSF samples from 48 patients, found the tests aided in resolving differential diagnoses, confirming disease recurrence or progression, aiding in disease stratification and supporting clinical trial workups – particularly in cases where traditional diagnostic methods like MRI, biopsy, and blood tests were inconclusive.¹

How the Liquid Biopsy Works

The Summit test detects clinically relevant variants, including single nucleotide variants (SNVs), multi-nucleotide variants (MNVs), and chromosomal arm-level alterations, using duplex next-generation sequencing and low-pass whole-genome sequencing.¹ Alterations are classified as clinically significant per AMP/ASCO/CAP guidelines. The test has a clinical sensitivity of 90% and a specificity of 95%, with a limit of detection of 0.3% variant allele frequency (VAF).¹

The updated version of the assay now includes analysis of indels in 488 additional genes, copy-number variants in 62 genes, fusions in 27 genes, tumor mutational burden, and microsatellite instability.

Key Findings of the Study

• Clinical Impact: Summit and Vantage provided meaningful clinical impact in 41 of 50 specimens (82%).^1,2
• Variant Detection: The Summit test detected clinically relevant variants in 64% (32 of 50) of specimens.^1,2
• Common Alterations: The most frequently detected gene alterations were MYD88, followed by TP53 and CD79B, which are critical to CNS lymphoma diagnosis.^1,2
• Aneuploidy: Aneuploidy findings were clinically significant, particularly in cases suspected of metastatic CNS lymphoma.¹
• Treatment Response: In two cases, longitudinal monitoring with the Summit test showed the absence of previously detected variants, suggesting a positive response to therapy.²
• Diagnostic Clarity: In one case, Summit was the only test to provide actionable information after MRI, biopsy, and blood-based testing yielded indeterminate results.^1,2

Implications for CNS Lymphoma Management

“The Summit assay has enabled molecular diagnoses in patients who were unable to undergo surgery, providing actionable clarity without the need for tissue,” said Michael Youssef, MD, neuro-oncologist at the University of Texas Southwestern Medical Center.² “The ability to longitudinally track variant allele frequency (VAF) has further strengthened our capacity to monitor treatment response in real time.”

The study highlights the potential of CSF liquid biopsy as a valuable tool for diagnosing and managing CNSL, especially in challenging cases where conventional methods are limited.

References

1. Larson A, Udhane V, Adams JN, et al. Demonstrating the impact of the Belay cerebrospinal fluid liquid biopsy tests Summit™ and Vantage™ to inform diagnosis and management of central nervous system lymphoma. Lymphat. 2026;4(1):9. doi:10.3390/lymphatics4010009
2. Belay Diagnostics reports 82% clinical impact rate for Summit™ and Vantage™ in CNS lymphoma study. News release. Belay Diagnostics. March 24, 2026. Accessed March 26, 2026.