Serial biopsies are not a realistic method for monitoring patients’ response to treatment or for assessing their prognosis. Liquid biopsies, an emerging technology that uses blood samples, however, can provide valuable information that allows oncologists to provide precision medicine.

In this article, Kathy Boltz, PhD, Oncology Nurse Advisor news writer, reports on a presentation by Matthew Krebs, MD, PhD, at the European Lung Cancer Conference in Geneva, Switzerland. Krebs discussed the development of liquid biopsy, and its use in the management of non-small cell lung cancer.

Liquid biopsy is a developing technology that offers a way to monitor tumor clonal evolution that facilitates precision medicine. Matthew Krebs, MD, PhD, of the Institute of Cancer Sciences at The University of Manchester in the United Kingdom described the development of both circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) for liquid biopsies. His session covered the promises and pitfalls of liquid biopsy for non-small cell lung cancer (NSCLC) at the European Lung Cancer Conference in Geneva, Switzerland.

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Krebs explained that serial biopsies are just not going to happen in the clinic. Although serial biopsies offer valuable information, they are not a practical reality. So, the development of liquid biopsies offers a promising alternative. Liquid biopsies, using blood samples, allow serial monitoring of patients.


Currently, the only validated system for CTCs is the CellTracks system. However, for NSCLC, its big drawback is that it is completely dependent on epithelial markers, and these particular markers are present in only about 15% of patients with NSCLC. Other systems to track CTCs are in development, but none are yet validated, Krebs stated.

The level of CTCs and their change after treatment offer prognostic information on patients. The number of CTCs is a strong indicator for overall survival—more CTCs predicts worse overall survival. Krebs explained that CTCs can detect ALK-gene rearrangement and expression, though measuring ALK in CTCs is technically challenging and not currently practical outside of dedicated research laboratories.

New technologies allow for single-cell analysis of CTCs. These are helpful in addressing questions on if the heterogeneity of CTCs reflects tumor heterogeneity, if different populations of cells have unique driver mutations, and which CTCs survive and result in metastases.

CTCs offer an excellent research tool, explained Krebs, who mentioned that his focus is phase 1 trials in NSCLC. CTCs allow the assessment of morphology, protein expression, and genetic aberrations all in the same cells.

Downsides of CTCs include the lack of validation and qualification for most technologies and the wide variations in CTC definitions and technologies. CTC technology also is expensive. It is difficult to reproduce assays across multiple sites, which limits the routine clinical use of CTCs now.