CSF Liquid Biopsy May Help Clarify Inconclusive Leptomeningeal Disease Cases, Study Finds

Belay Diagnostics peer-reviewed study shows variant allele frequency measured from CSF may support diagnosis and monitoring in leptomeningeal disease

CHICAGO, April 14, 2026 /PRNewswire/ -- Leptomeningeal disease (LMD) remains one of the most challenging diagnoses in neuro-oncology. MRI returns normal or inconclusive results in 20 to 30 percent of confirmed cases, and CSF cytology can miss roughly 1 in 3 patients at initial testing.

A new peer-reviewed study published in Diagnostics suggests that a standard lumbar puncture may help address this diagnostic gap. By measuring variant allele frequency (VAF) in tumor-derived DNA from CSF using the Summit™ liquid biopsy assay, clinicians gain specific, quantitative signals to support diagnosis and monitor treatment response over time.

Key Findings

The study analyzed 118 CSF specimens from patients with a provisional diagnosis of metastatic CNS cancer, spanning breast, lung, and other primary malignancies. Summit™ identified clinically significant variants in all 118 specimens across 22 of the 32 genes on the panel, including TP53, EGFR, KRAS, and PIK3CA.

A VAF threshold of 5 percent emerged as a potentially meaningful marker for LMD. Sixty-nine percent of patients with confirmed LMD had VAFs above that threshold, while most patients with parenchymal metastases or unconfirmed LMD had VAFs below 5 percent. In cases where imaging and cytology were inconclusive, an elevated VAF prompted further investigation that ultimately led to confirmed LMD diagnoses. In 10 additional cases initially categorized as parenchymal metastases or suspected LMD, VAFs above 5 percent were later associated with confirmed LMD on clinical or pathological follow-up.

For patients in treatment, serial CSF testing with Summit showed that VAF changes tracked clinical outcomes. Half of patients (7 of 14) with repeat testing showed decreasing or absent VAF following treatment, correlating with clinical improvement. In one patient, a rising VAF likely corresponded with disease progression. In three cases, a new variant appeared on repeat testing, suggesting clonal evolution or spatial heterogeneity within the leptomeningeal space, a finding that indicates serial CSF liquid biopsy may capture how tumor genomics evolve over time.

"This study illustrates how liquid biopsy with the Belay assay represents a paradigm shift in neuro-oncology. This technology allows for the continuous monitoring of a tumor's molecular evolution, enabling physicians to detect clonal evolution and possibly treatment resistance ahead of radiographic progression, closing the gap between biological change and clinical intervention," said Nancy Ann O. Bush, MD, PhD, Clinical Director, Division of Neuro-Oncology, Department of Neurological Surgery and Neurology, University of California, San Francisco.

This work provides the foundation for prospective validation in larger, tumor-specific cohorts.

Read the full study: belaydiagnostics.com/lmd-study

About Belay Diagnostics

Belay Diagnostics is a Chicago-based laboratory dedicated to serving patients and the clinicians who care for them. Using licensed technology developed through more than 10 years of scientific research at Johns Hopkins University, Belay has developed three proprietary CSF liquid biopsy tests — Summit™, Ascent™, and Vantage™ — developed and validated to help inform the diagnosis and management of primary and secondary CNS malignancies. Belay's tests provide clinicians with comprehensive molecular insights from a standard lumbar puncture. No biopsy required. For more information, visit belaydiagnostics.com.

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SOURCE Belay Diagnostics