Despite the terminology “liquid biopsies” (LBx) becoming common place in diagnostic lexicon, as a routine clinical technology, LBx is still very much in its infancy. Liquid biopsy has a broad definition with a narrow connotation. Generally speaking, LBx is testing of biofluids including blood, urine, saliva and cerebral spinal fluid in lieu of more conventional (tissue) biopsies or assessment (imaging) approaches. In reality, mention of LBx recalls blood or plasma based testing. More specifically circulating tumor DNA (ctDNA), and to a lesser extent, circulating tumor cell (CTC) testing.

Benefits of liquid biopsy testing include:

  • Minimally invasive – A blood draw would be attainable in those patients who are unable to undergo tissue biopsy due to health risks of an invasive biopsy procedure.
  • Tumor site agnostic – tissue biopsies are limited to sampling site while LBx can inform on all (metastatic) tumor sites
  • Real time profiling – archival tissue biopsies can be years old and vaguely representative of the patient’s current tumor. ctDNA has a half-life of hours and can be sampled repeatedly to give a more current mutational profile.
  • Faster lab results – LBx averages about 2 weeks quicker results versus tissue testing
  • Earlier detection of recurrence – In some settings, LBx can detect recurrence weeks to months before conventional imaging approaches.
  • The first approved ctDNA LBx assay was in 2016 with Roche’s Cobas EGFR Mutation Test V2. Since then we’ve seen three more approvals consisting of qPCR and NGS covering both centralized and decentralized CDx models, thereby firmly paving pathways for ctDNA LBx as a CDx technology.
  • There are many more lessons to be learned as the field of LBx evolves but some key take away’s and trends currently are:
  • LBx will not replace tissue. It’s not a 1 for 1, but rather complementary tools.
  • LBx has quickly leaped from qPCR into NGS. As the field of molecular testing is moving away from single target platforms, future LBx approvals will likely all be NGS based.
  • In addition to LBx for therapy guidance, we expect to see LBx advancing diagnostic applications such as treatment and surveillance monitoring. There is a trend for personalized NGS assays which touts extremely high sensitivity.
  • More clinical data on LBx in different disease settings will be critical to understand where LBx can and should be applied as well as drive adoption.
  • There is an urgent need for standardization across LBx assays. Qualified standards, controls and QC materials are being developed and marketed. These will help to support analytical validation studies such as limit of detection.
  • Growth of LBx in global markets may be slower due to technology hurdles coupled with the risk of sample stability during international transit.

What is evident is that the momentum and fervor for the LBx field is accelerating. We see more dedicated LBx conferences, seminar tracks, and at NeoGenomics’, projects including a LBx component are becoming more common. But with all of the excitement, there is still much more work that is needed for liquid biopsies to be broadly accepted into routine practice.

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About James Yen, PhD

Principal Scientist, Associate Scientific Director, CDx Programs

About James Yen, PhD

Principal Scientist, Associate Scientific Director, CDx Programs

Dr. James Yen is a Senior Scientific Manager within NeoGenomics’ Pharma Services division. He completed his doctorate studies at UC Irvine studying the mechanism of protein degradation. Afterwards, he began working at Zymo Research (Irvine, CA) to lead the development of research reagents and kits for the study of epigenetics. He subsequently joined MDxHealth (Irvine, CA) in 2011 to setup their CLIA/CAP lab operations within the US and worked in both the clinical operations and product development teams as a senior scientist. In 2014, James joined Clarient (GE Healthcare) to manage the Pharma Services molecular and FISH operation teams. NeoGenomics acquired Clarient from GE Healthcare in 2015, and his current role is as a scientific liaison with a focus on NeoGenomics’ molecular, FISH and companion diagnostic service offerings.

These articles reflect the views of a group of experienced practitioners in subspecialty practice, with the goal to provide practical and useful guides to a specific diagnosis or problem area.