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Liquid Biopsy Diagnosis of CNS Metastases

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Central Nervous System Metastases

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Abstract

The application of liquid biopsy approaches to diagnose cancer and to monitor treatment response has rapidly grown in the last 5 years. The liquid biopsy analysis provides an opportunity to obtain complementary molecular information from different bodily fluids (e.g., blood, urine, cerebrospinal fluid) that may allow for improved management of cancer patients. Apart from cytological and biochemical analysis of cerebrospinal fluid (CSF), the use of liquid biopsy as a diagnostic tool for central nervous system (CNS) metastases is still in its early stage. Identification and more extensive characterization of tumor cells and proteins, but also of circulating tumor DNA (ctDNA) and different forms of RNA in CSF, is increasingly pursued in order to improve the diagnosis and management of patients with CNS metastases. Furthermore, the utility of liquid biopsies for monitoring treatment responses of patients with CNS metastases is beginning to be explored. Although several challenges remain, current technological progress in assay development will allow to tackle limitations imposed by lack of standardized and validated methods for liquid biopsy-based diagnostics of CNS metastases. Inclusion of liquid biopsies in the design of longitudinal cohort studies with combined analysis of various liquid biopsy biosources is expected to advance the discovery of reliable molecular biomarkers for prediction and early detection of CNS metastases. As the result, novel treatment modalities may become available for patients at high risk of CNS metastases, preventing their future occurrence and thereby improving patient outcomes.

Mafalda Antunes Ferreira and Silvia D’Ambrosi are co-first authors.

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Abbreviations

BCAAs:

Branched-chain amino acids

cfDNA:

Cell-free DNA

cfRNA:

Cell-free RNA

circRNA:

Circular RNA

CNAs:

Circulating nucleic acids

CNS:

Central nervous system

CNV:

Copy number variation

CPs:

Circulating proteins

CSF:

Cerebrospinal fluid

CTC:

Circulating tumor cell

ctDNA:

Circulating tumor-derived DNA

CUP:

Carcinoma of unknown primary

ddPCR:

Digital droplet PCR

dsDNA:

Double-stranded DNA

EGFR:

Epidermal growth factor receptor

EMA:

European Medicines Agency

EMT:

Epithelial to mesenchymal transition

EpCAM:

Epithelial cell adhesion molecule

ESMO:

European Society of Medical Oncology

EVs:

Extracellular vesicles

FC:

Flow cytometry

FDA:

US Food and Drug Administration

FFPE:

Formalin-fixed paraffin-embedded

HER2:

Human epidermal growth factor receptor

IVD:

Diagnostic medical device

LDH:

Lactate dehydrogenases

LM:

Leptomeningeal metastases

lncRNA:

Long non-coding RNA

LOH:

Loss of heterozygosity

miRNA:

Micro-RNA

mRNA:

Messenger RNA

NGS:

Next-generation sequencing

NSCLC:

Non-small cell lung cancer

PCR:

Polymerase chain reaction

PPV:

Positive predictive value

PSO:

Particle swarm optimization

ssDNA:

Single-stranded DNA

TEPs:

Tumor-educated platelets

TME:

Tumor microenvironment

WES:

Whole-exome sequencing

WGS:

Whole-genome sequencing

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Acknowledgments

The authors apologize for not citing all the studies, technologies, and clinical trials on the topic of liquid biopsies and CNS metastases in this chapter. The authors thank L. Salvador for his assistance in drafting the figure included in this chapter. The work of authors M.A.F., S.D., D.K.L., and T.W. is supported by H2020 MSCA ITN ELBA GA#765492, and D.K.L. is a recipient of the Dutch Cancer Foundation grant (KWF2017-10476) and the Cancer Center Amsterdam foundation grant (CCA2017-2-16).

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Authors and Affiliations

  1. Department of Neurosurgery, Cancer Center Amsterdam, Amsterdam Universities Medical Centers/VU University Medical Center, De Boelelaan 1117, Amsterdam, 1081 HV Amsterdam, The Netherlands

    Mafalda Antunes Ferreira, Silvia D’Ambrosi, Thomas Würdinger & Danijela Koppers-Lalic

  2. Department of Pathology, Brain Tumor Center Amsterdam, Amsterdam Universities Medical Centers/VU University Medical Center, Amsterdam, The Netherlands

    Pieter Wesseling

  3. Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands

    Pieter Wesseling

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  1. Mafalda Antunes Ferreira
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  2. Silvia D’Ambrosi
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Correspondence to Danijela Koppers-Lalic .

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Editors and Affiliations

  1. Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, OH, USA

    Manmeet Ahluwalia

  2. Department of Neurosurgery and Neuro-Oncology, Clairval Hospital Center, Ramsay-Générale de Santé, Marseille, France, Neurophysiopathology Institute, Aix-Marseille Université, Marseille, France

    Philippe Metellus

  3. Department of Neuro-Oncology, University and City of Health and Science Hospital, Turin, Italy

    Riccardo Soffietti

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Antunes Ferreira, M., D’Ambrosi, S., Würdinger, T., Wesseling, P., Koppers-Lalic, D. (2020). Liquid Biopsy Diagnosis of CNS Metastases. In: Ahluwalia, M., Metellus, P., Soffietti, R. (eds) Central Nervous System Metastases. Springer, Cham. https://doi.org/10.1007/978-3-030-23417-1_6

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