CSF Liquid Biopsy Displays 82% Clinical Impact in CNS Lymphoma

Summit™ and Vantage™, cerebrospinal fluid (CSF) liquid biopsies, displayed a clinically meaningful impact in 82% of central nervous system lymphoma (CNSL) cases, according to findings from a retrospective analysis including 50 CSF samples and 48 patients published in Lymphatics.¹

Specifically, the Summit test detected significant variants, by gene level alteration, chromosomal arm level alteration, and/or MGMT promoter methylation per Tier 1 or 2 classification per AMP/ASCO/CAP guidelines, in 32 of 50 samples (64%). Additionally, clinical follow-up of negative cases post-biopsy confirmed 9 of 18 (50%) to be negative, with 2 confirmed as false negatives. The cases impacted by the CSF liquid biopsy tests helped to inform diagnosis, support clinical suspicion of disease progression or recurrence, and confirm therapeutic responses, according to the investigators of the study.

The most commonly altered gene was MYD88 followed by TP53, with gene level variants observed in 100% of positive cases (n = 17) with a provisional or final diagnosis of primary CNSL and 60% (n = 9/15) of secondary CNSL-positive cases. Aneuploidy was detected in 29% (n = 5/17) and 73% (n = 11/15) of each group. Moreover, clinically actionable variants were detected in 70% (n = 26/37) of samples aiding in diagnosis of CNSL.

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

In 13 specimens for which CNSL was diagnosed prior to testing, the CSF test detected clinically significant variants in 6 of 13 cases, with all found to contain at least 1 loss of function variant in TP53. Moreover, the Summit test was used for longitudinal monitoring in 2 cases, with the absence of previously detected variants suggesting response to therapy, according to the investigators.

Patients in the analysis underwent tissue collection between September 2024 and September 2025, with orders placed as part of initial CNSL diagnostic work-up for 37 samples. Furthermore, 13 were placed for an initial diagnosis based on order test requisition form. Moreover, clear indication for testing with parallel diagnostic work-up results was available for 43 of the orders. Findings for these orders were reviewed and contextualized by accompanying clinical documentation.

The impact of Belay testing was determined by a review of variant clinical actionability per AMP/ASCO/CAP classification guidelines as well as integration of NCCN/WHO guidelines in the context of differential and provisional diagnoses and oncology history for individual cases in addition to clinician follow-up.

The Summit test assesses single nucleotide variants (SNVs) and multi-nucleotide variants (MNVs) in a 32-gene panel through the use of duplex next-generation sequencing powered by proprietary MethylSaferSeqS in addition to chromosomal arm-level changes using low-pass whole-genome sequencing. Tier 1 or 2 alterations, deemed clinically significant, are classified as such per AMP/ASCO/CAP guidelines. Moreover, the Summit test is validated in CSF with a clinical sensitivity of 90%, a specificity of 95%, and a limit of detection of 0.3% VAF.

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

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. https://tinyurl.com/y5ttcrmj