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The Promise of Liquid Biopsy: A Q&A with Professor Sandi Deans

Posted by Krystyna Nahlik, PhD on Mar 4, 2021

 

This is Part 1 in a 3- series deep-dive Q&A with expert panelists addressing many of the issues faced in developing and deploying NGS-based liquid biopsy assays for clinical applications in oncology.

At the 2020 liquid biopsy webinar, Professor Sandi Deans highlighted a recent EQA scheme aimed at evaluating the standard of cfDNA testing in NSCLS and CRC patients. It was driven by demand from participants themselves, as well as pharmaceutical companies, IVD manufacturers and IQNPath (International Quality Network for Pathology).

A smaller pilot study1 to help understand challenges associated with different sample types, testing strategies and methodologies that determine test limitations was followed by global rollout to over 300 laboratories, with enormous demand. The accompanying survey revealed a wide array of extraction methods and testing methodologies used, with NGS and Roche Cobas assays leading the way, followed by ddPCR and other approaches. Even for a very challenging sample included in the EQA containing two EGFR mutations, p.L858R and p.T790M at low VAFs, majority of the testing laboratories reported the correct genotype for both variants, with highest accuracy for p.T790M variant due to higher sensitivity of most analysis methods to this important EGFR variant.

Sometimes when a mutation was not reported, it may be due to either reporting policies or the stated limit of detection of the method performed being above the variant allele frequency. This highlights the importance of efforts toward reporting and terminology harmonization, especially regarding limit of detection and units, to achieve clarity on what parameters each assay is testing and detecting, and at what level of sensitivity.

Representatives of participating laboratories discussed all of these topics during a workshop held after the EQA scheme concluded, with the aim of setting guidelines for achieving quality implementation of cfDNA testing in the clinical setting.2 This would allow moving on to evaluation of more complex multi-gene targets in cfDNA including INDELs and gene fusions, which is a challenging and still evolving field, as well as cfRNA testing that is of growing interest.

Q&A with Professor Deans:

What would be your advice to those moving from tissue to ctDNA testing for the first time?
Professor Deans: Define your clinical needs very clearly; understand the limitations of the test you will perform; determine the LoD and level of reporting before choosing the method and have a robust validation plan including reference materials from the outset.

In the challenging sample sent out to participating clinical laboratories, did you specify how many ng of DNA the labs should use for analysis?
Professor Deans: For EQA purposes, the laboratories are required to follow routine protocols, so we do not specify how much DNA is required for testing. The aim of EQA is to assess the clinical service provided by the laboratory and not to ‘pass the EQA’.

What is your view concerning centralized versus in-house liquid biopsy testing?
Professor Deans: It depends on local set-up. For rapid turnaround times, a local testing strategy may be required, however high throughput testing in a centralized laboratory will bring costs down and may help turnaround times, as there is no need to wait to batch samples.

Guidelines are in place for the use of liquid biopsy at recurrence as an alternative for tissue biopsy. Would you suggest that liquid biopsy could replace tissue at the point of diagnosis too?
Professor Deans: It will always be an option when clinically required e.g. very ill patients to aid diagnosis.

What do you see as the next steps in liquid biopsy studies?
Professor Deans: More targets added to testing so more information from a single NGS panel test.

Download the video to replay or watch the webinar The Promise of Liquid Biopsy for Cancer Diagnostics and Therapeutic Monitoring: Are We There Yet?


References:

  1. Keppens, C., Dequeker, E.M.C., Patton, S.J. et al. “International pilot external quality assessment scheme for analysis and reporting of circulating tumour DNA”. BMC Cancer 18, 804 (2018). https://doi.org/10.1186/s12885-018-4694-x
  2. Deans, Zandra C et al. “IQN path ASBL report from the first European cfDNA consensus meeting: expert opinion on the minimal requirements for clinical ctDNA testing.” Virchows Archiv : an international journal of pathology vol. 474,6 (2019): 681-689. https://doi.org/10.1007/s00428-019-02571-3

Topics: NGS, ctDNA, cfDNA, reference materials, ccfDNA