New Breakthroughs in the Diagnosis of Leptomeningeal Carcinomatosis: A Review of Liquid Biopsies of Cerebrospinal Fluid

Abstract

Leptomeningeal carcinomatosis represents a terminal stage and is a devastating complication of cancer. Despite its high incidence, current diagnostic methods fail to accurately detect this condition in a timely manner. This failure to diagnose leads to the refusal of treatment and the absence of clinical trials, hampering the development of new therapy strategies. The use of liquid biopsy is revolutionizing the field of diagnostic oncology. The dynamic and non-invasive detection of tumor markers has enormous potential in cancer diagnostics and treatment. Leptomeningeal carcinomatosis is a condition where invasive tissue biopsy is not part of the routine diagnostic analysis, making liquid biopsy an essential diagnostic tool. Several elements in cerebrospinal fluid (CSF) have been investigated as potential targets of liquid biopsy, including free circulating tumor cells, free circulating nucleic acids, proteins, exosomes, and even non-tumor cells as part of the dynamic tumor microenvironment. This review aims to summarize current breakthroughs in the research on liquid biopsy, including the latest breakthroughs in the identification of tumor cells and nucleic acids, and give an overview of future directions in the diagnosis of leptomeningeal carcinomatosis.

Keywords: brain metastases; brain spine tumors; leptomeningeal carcinomatosis; liquid biopsy; neuro oncology.

Figure 1. Example of LMD with T1 contrast-enhanced lesions in brain (A) and spine (B).

LMD: leptomeningeal disease. Note: This image is the author's own creation.

Figure 2. Methods to diagnose leptomeningeal carcinomatosis.

Note: This image is created by Biorender.com.