Liquid Biopsy of Cerebrospinal Fluid More Effective in Managing Brain Tumors

Liquid biopsy of cerebrospinal fluid (CSF) has potential for prognosis, treatment, identification, and tracking of brain tumor genomic alterations both in real time and over time. Concentrations of circulating central nervous system tumor DNA are very low in plasma, but very high in CSF, according to the findings, published in Nature Communications (2015; doi:10.1158/2159-8290.CD-15-0369).

A liquid biopsy in CSF, obtained by lumbar puncture, is much less invasive and less risky for the patient than traditional procedures used to extract brain tissue samples. Findings also show that this circulating tumor DNA can both facilitate and complement the diagnosis of leptomeningeal carcinomatosis (LC).

The identification of each and every tumor type along with each respective, individual molecular makeup is critical in tackling cancer with greater precision. To date, extraction of brain tumor tissue for analysis has consisted of a punch biopsy or surgery. Such approaches have risk and do not necessarily facilitate access to a representative part of the tumor.

The novel technique of liquid biopsy detects a tumor's specific mutations by means of a plasma sample containing circulating tumor DNA. It allows treatments to stay ahead of cancer's next move, while being much less invasive than traditional biopsy techniques.

"With these important considerations in mind we looked for a way to apply this type of liquid biopsy to brain cancer, especially in view of the obstacles associated with accessing this tumor type," explained study leader Joan Seoane, PhD, director of Translational Research at the Vall d'Hebron Institute of Oncology, Catalan Institution for Research and Advanced Studies (ICREA) Professor, and professor at the Universitat Autònoma de Barcelona (UAB) in Barcelona, Spain.

Liquid biopsy in plasma has already proven useful for metastatic colon, breast, and lung cancers, but not as successful for brain tumors, for several reasons.

"Our main limitation was that circulating tumor DNA levels for brain tumors are very low in plasma. But the brain has its own closed circuit of fluid, cerebrospinal fluid, which bathes the brain and spinal cord, and is therefore in direct contact with tumor cells," continued Seoane, "and we found circulating tumor DNA in CSF at such high levels that we were able to detect and characterize tumors with a high degree of sensitivity".

Glioblastoma is the most common and aggressive malignant brain tumors, and it almost always recurs, often in a form that requires different therapy than the first tumor.

"Mirroring certain successes to-date of applying liquid biopsy across other tumor types, the use of tumor DNA circulating in CSF as a liquid biopsy for brain tumors could be much less invasive than standard tissue biopsy to characterize the genetic alterations of the new tumor. This new approach to liquid biopsy in CSF could help, in some cases, to consider novel, more specific and targeted experimental therapies, which could in turn also improve clinical response," explained coauthor Josep Tabernero, MD, director of VHIO, head of the Medical Oncology Department of Vall d'Hebron University Hospital.

The study also focused on leptomeningeal carcinomatosis, which is the tumor infiltration of the fine film that covers the brain and spinal cord and occurs as a metastasis of other tumors. Its diagnosis is complicated on imaging tests and the possibility of catching a tumor cell for study by lumbar puncture is remote.

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