Abstract
Simple SummaryThe optimal treatment and management of patients with brain cancer depend on the molecular characteristics of their tumour. Since the tumour changes with time, it is, therefore, essential to characterise the tumour of each patient at the exact time of selecting the most suitable therapeutic strategy. However, obtaining a tumour biopsy for its characterisation is a risky and invasive procedure and, sometimes, not even feasible, leading to a lack of information about the tumour. These challenges can be overcome by using a liquid biopsy of cerebrospinal fluid. Brain cancer cells release DNA into the cerebrospinal fluid, and the analysis of the cell-free circulating tumour DNA can reveal the genetic profile of brain cancer in a relatively noninvasive manner. In this review, we revise the recent results in this field that show how circulating tumour DNA in cerebrospinal fluid can provide diagnostic and prognostic information, identify potential therapeutic targets, monitor the tumour response or resistance to treatment, and help to identify tumour relapse.The correct characterisation of central nervous system (CNS) malignancies is crucial for accurate diagnosis and prognosis and also the identification of actionable genomic alterations that can guide the therapeutic strategy. Surgical biopsies are performed to characterise the tumour; however, these procedures are invasive and are not always feasible for all patients. Moreover, they only provide a static snapshot and can miss tumour heterogeneity. Currently, monitoring of CNS cancer is performed by conventional imaging techniques and, in some cases, cytology analysis of the cerebrospinal fluid (CSF); however, these techniques have limited sensitivity. To overcome these limitations, a liquid biopsy of the CSF can be used to obtain information about the tumour in a less invasive manner. The CSF is a source of cell-free circulating tumour DNA (ctDNA), and the analysis of this biomarker can characterise and monitor brain cancer. Recent studies have shown that ctDNA is more abundant in the CSF than plasma for CNS malignancies and that it can be sequenced to reveal tumour heterogeneity and provide diagnostic and prognostic information. Furthermore, analysis of longitudinal samples can aid patient monitoring by detecting residual disease or even tracking tumour evolution at relapse and, therefore, tailoring the therapeutic strategy. In this review, we provide an overview of the potential clinical applications of the analysis of CSF ctDNA and the challenges that need to be overcome in order to translate research findings into a tool for clinical practice.
Highlights
Central nervous system (CNS) malignancies affect both children and adults worldwide and are responsible for substantial morbidity and mortality
An epidemiological study of central nervous system (CNS) cancer between 1990 and 2016 revealed that the age-standardised incidence rate has increased by 17.3% globally, with 330,000 incident cases and 227,000 deaths globally in CNS cancer consists of primary tumours and intracranial metastases
The availability of targeted therapies highlights the importance of the identification of actionable genomic alterations or resistance mutations in genes, including epidermal growth factor receptor (EGFR), ALK, BRAF and HER2, which have been detected from cerebrospinal fluid (CSF) circulating tumour DNA (ctDNA) in several studies [20,21,31,32,94,95,96]
Summary
Central nervous system (CNS) malignancies affect both children and adults worldwide and are responsible for substantial morbidity and mortality. The known evolution of tumours and the absence of longitudinal tumour sampling may, lead to imprecise diagnosis and clinical management For these reasons, there is an urgent need to develop less invasive methods to identify and validate tumour biomarkers that provide real-time information to aid in diagnosing and monitoring CNS malignancies. There is an urgent need to develop less invasive methods to identify and validate tumour biomarkers that provide real-time information to aid in diagnosing and monitoring CNS malignancies Overall, this will help to adjust the therapeutic strategy and guide treatment decisions based on the current tumour profile and its burden. The levels of ctDNA in CSF may be influenced by tumour burden, tumour progression and anatomical location of the tumour, with regard to the proximity to CSF reservoirs [21,22,23]
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