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Liquid Biopsy Diagnosis of CNS Metastases

  • Mafalda Antunes Ferreira
  • Silvia D’Ambrosi
  • Thomas Würdinger
  • Pieter Wesseling
  • Danijela Koppers-LalicEmail author
Chapter

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.

Keywords

Liquid biopsy CNS metastases CSF Blood Biosources DNA RNA 

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

Notes

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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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Mafalda Antunes Ferreira
    • 1
  • Silvia D’Ambrosi
    • 1
  • Thomas Würdinger
    • 1
  • Pieter Wesseling
    • 2
    • 3
  • Danijela Koppers-Lalic
    • 1
    Email author
  1. 1.Department of NeurosurgeryCancer Center Amsterdam, Amsterdam Universities Medical Centers/VU University Medical CenterAmsterdamThe Netherlands
  2. 2.Department of PathologyBrain Tumor Center Amsterdam, Amsterdam Universities Medical Centers/VU University Medical CenterAmsterdamThe Netherlands
  3. 3.Princess Maxima Center for Pediatric OncologyUtrechtThe Netherlands

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