The characterization of brain tumors using circulating tumor DNA (ctDNA) from cerebrospinal fluid (CSF) may be a feasible approach in the near feature, according to a recent review of the method.1

“Invasive surgical procedures have been the cornerstone treatment and a diagnostic tool in patients with primary brain tumors and in selected patients with brain metastasis,” the review authors wrote. “However, collecting tumor tissue from central nervous system (CNS) malignancies is complex, can be risky, and sometimes unfeasible, at least with purely diagnostic intent.”1

The use of plasma cell-free ctDNA — liquid biopsy — has shown promise in characterizing tumors and monitoring them over time, but its use in primary brain tumors and brain metastases has been limited. However, recent studies have shown that CSF contains ctDNA, and the examination of this ctDNA has been explored as an approach to characterize brain cancers.

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Looking at primary brain tumors, studies have shown that CSF ctDNA is detected in a large proportion of patients, but not in all brain tumors, meaning that the potential therapeutic implications of using ctDNA in this way would still be limited to certain patients.

“The most relevant biomarker for glioblastoma in terms of choice of therapy remains promoter methylation of the MGMT gene. Efforts at the detection of MGMT promoter methylation in CSF of glioma patients showed higher sensitivity than in plasma,” the authors wrote. “Future applications with therapeutic impact are likely to include the monitoring of EGFRvIII and amplified EGFR in patients undergoing EGFR-targeted therapy.”

Early research into brain metastases has shown that CSF ctDNA analysis captured trunk mutations and private mutations to the brain and meningeal deposits, highlighting “the potential applications of cerebrospinal fluid ctDNA to complement diagnosis of brain metastasis.”

The method is not without other limitations however, the authors noted. Among these limitations are that existing data is mainly from small cohorts of patients, there is the potential for blood contamination in the CSF sample, or the short time interval between surgery and when the fluid analysis evaluating ctDNA would have to occur. In addition, many more questions and controversies will need to be resolved before the method can be used in clinical practice.

Nevertheless, “liquid biopsy approaches based on cerebrospinal fluid are opening new avenues for the better managing of brain cancer patients,” the authors concluded.


  1. Seoane J, De Mattos-Arruda L, Le Rhun E, Bardelli, A, Weller, M. Cerebrospinal fluid cell-free tumour DNA as a liquid biopsy for primary brain tumours and central nervous system metastases [published online December 21, 2018]. Ann Oncol. doi: 10.1093/annonc/mdy544