Abstract

As therapies have become more and more dependent on tumor as well as patient characteristics, obtaining tumor material has become of great importance. Liquid biopsies hold much potential as shown by a large amount of evidence across several studies. Clinical applications for circulating tumor cells (CTCs) are unfortunately still lacking. In part this is due to a lack of studies comparing liquid biopsies to conventional diagnostics and response measurements as well as studies showing that liquid biopsies can be used to switch therapies leading to improved outcomes. However, liquid biopsies using ctDNA for specific markers such as EGFR, ALK, ROS1 or RET have clinical applications because specific drugs are available.

Highlights

  • As therapies therapies have have become become more more and and more more dependent dependent on on tumor tumor as as well characteristics, obtaining tumor material has become of great importance

  • ROS1 liquid biopsies using circulating tumor DNA (ctDNA) for specific markers such as EGFR, ALK, ROS1 or RET have or RET have because clinical applications because specific drugs are available

  • All CTC numbers are in 7.5 mL of whole blood, unless stated otherwise. *: OS: overall survival, PFS: progression-free survival, DFS: disease-free survival, HR: hazard ratio. §: ISET: isolation by size of epithelial tumor. ∆: EpCAMCTCs: epithelial cell adhesion molecule negative circulating tumor cells. #: HD-CTC IF: high definition-CTC

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Summary

Tumor Tissue Obtained from Primary Tumors or Metastases

For optimal treatment decision-making, the histological classification, the presence of targetable mutations, immune cells and surface molecules (e.g., PD-L1) are important. This information is routinely obtained using formaline-fixed, paraffine-embedded tissue blocks from tumor biopsies. About 20%–25% of endoscopic biopsies do not provide enough tumor cells to perform molecular predictive testing or the DNA is of low quality [10]. Sometimes they do not even contain enough tumor cells for a well-established histopathological examination. Biopsies are invasive for the patient and not without complications

Liquid Biopsies
Circulating Tumor Cells
Measurement Method
Circulating Cell-Free DNA
Findings
Required Steps before Clinical Implementation Can Be Considered
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