NCCN Now Backs CSF Genomic Testing in Gliomas When Biopsy Isn't Possible

The National Comprehensive Cancer Network (NCCN) has expanded its Clinical Practice Guidelines in Oncology for central nervous system (CNS) cancers to recommend cerebrospinal fluid (CSF)-based molecular tumor profiling for patients with high-grade glioma (HGG) or glioblastoma (GBM) when tissue biopsy is not feasible.¹

The update applies regardless of why surgery or biopsy cannot be performed, whether due to tumor location, patient health status, or patient refusal, and is intended particularly for cases in which molecular characterization is needed to establish a diagnosis or guide treatment selection. The change places inoperable HGG and GBM alongside a growing list of CNS malignancies for which NCCN already recommends CSF-based testing, including medulloblastoma, spinal and cranial ependymoma, primary CNS lymphoma, and leptomeningeal metastasis in adults.

This marks the second consecutive year that NCCN has broadened the scope of CSF-based molecular profiling within its CNS cancer guidelines. The trend reflects a wider push to apply liquid biopsy methods already established in solid tumor oncology to brain and spinal cord malignancies, where tissue sampling carries substantially higher procedural risk. For patients in whom biopsy is not an option, management has historically relied on imaging and CSF cytology alone, an approach that does not provide the molecular detail increasingly required for diagnosis and therapy selection under current World Health Organization classification standards.

CSF-based comprehensive genomic profiling (CGP) analyzes tumor-derived nucleic acids shed into the cerebrospinal fluid, offering a route to molecular characterization without traversing the blood-brain barrier, a limitation that has made plasma-based liquid biopsy largely ineffective for CNS tumors. The NCCN guidelines also specify that pathologic characterization of CNS tumors be performed using multi-gene panel testing capable of assaying multiple biomarkers from a single specimen, a method compatible with CSF-based CGP platforms.

Belay Diagnostics offers 3 CSF-specific tests for CNS malignancies: Summit 2.0, Ascent, and Vantage. Each can be run on a single CSF specimen obtained through a standard lumbar puncture. The company's flagship CGP panel, Summit 2.0, was validated in a study published in the peer-reviewed journal Cancers.² The analytical validation, conducted across 68 specimens, demonstrated detection of all variant types using as little as 15 nanograms of CSF-derived total nucleic acid, with an analytical sensitivity of 96.7% for single nucleotide variants and insertions/deletions and a 100% limit of detection at a variant allele frequency of 0.3%. Clinical validity was assessed in a cohort of 118 CSF specimens spanning primary and metastatic CNS tumors, yielding 96% clinical sensitivity and 98% clinical specificity when measured against tissue-matched or definitively diagnosed samples. The study's authors noted that current NCCN guidelines for CNS cancers recommend next-generation sequencing-based comprehensive genomic profiling as the preferred approach for molecular characterization, citing the infeasibility of tissue-based testing for many patients and the limitations the blood-brain barrier imposes on plasma-based liquid biopsy.

REFERENCES

1. Belay Announces Update to NCCN Guidelines to Recommend CSF-based Genomic Profiling in Biopsy Infeasible High-Grade Gliomas. News release. Belay Diagnostics. June 17, 2026. Accessed June 17, 2026. https://tinyurl.com/ys8rftjr

2. Khurana S, Keo V, Larson A, et al. Analytical Validation and Clinical Sensitivity of the Belay Summit 2.0 Cerebrospinal Fluid Liquid Biopsy Test—An Expanded Comprehensive Genomic Profiling Platform for Central Nervous System Malignancies. Cancers (Basel). 2026;18(2):256. doi:10.3390/cancers18020256