Spinal Fluid Liquid Biopsy May Help Clarify Uncertain Brain Tumor Findings

MRI changes may reflect cancer, inflammation, or treatment-related effects, while the blood-brain barrier can limit tumor DNA detection through blood-based liquid biopsy. Given these limitations, new research highlights cerebrospinal fluid DNA testing as a potential source of additional diagnostic information in challenging neuro-oncology cases.

Mayo Clinic (Rochester, MN, USA) researchers evaluated cerebrospinal fluid (CSF) cell-free DNA molecular profiling in patients with unresolved diagnostic questions involving the brain or spinal cord. The approach examines DNA fragments released by tumor cells into CSF, the clear fluid surrounding these structures. Samples collected by lumbar puncture are analyzed for individual gene changes and broader DNA patterns associated with tumors.

The study included 76 patients across three clinical scenarios: 35 had an undiagnosed brain or spinal cord abnormality, 21 had imaging changes that could indicate either tumor progression or treatment-related effects, and 20 were being evaluated for suspected leptomeningeal disease. This condition occurs when cancer spreads to the membranes and fluid surrounding the brain and spinal cord.

Tumor-associated DNA was detected in 20 patients, or 26% of the cohort. Samples from another 29 patients contained sufficient DNA for analysis but showed no tumor DNA, while 27 samples lacked enough usable DNA to complete testing. These results require careful interpretation, as the researchers noted that a negative finding did not rule out cancer: the amount of tumor DNA released into CSF can vary.

Published in the Journal of Neuro-Oncology, the findings concern a test that remains investigational. Tumor tissue remains the gold standard for definitive diagnosis when it can be obtained safely. To further develop the approach, researchers are working to improve analysis of low-DNA samples and determine whether tracking DNA changes and other biomarkers over time could help assess treatment response.

“Our goal is for CSF cell-free DNA testing to provide patients and their care teams with diagnostic insights when answers may otherwise be difficult to obtain. As we gain more experience, we hope it will also help connect patients with clinical trials and personalized treatment options,” said Cecile Riviere-Cazaux, a Mayo Clinic Alix School of Medicine student in Rochester and co-first author of the study.

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