An important goal in cancer disease management is early detection. When detected early, disease progression can be significantly mitigated with a plethora of options (targeted therapy, chemotherapy, surgery, etc.) available to medical practitioners, to afford progression free survival and a higher quality of life. A great promise of liquid biopsies is the possibility of early detection of cancer long before clear evidence of lesions and tumor growth observable by imaging or other techniques.1 As proxy for solid tissue biopsies, plasma-based liquid biopsy application is rapidly gaining traction in cancer disease diagnosis, progression, monitoring, and in predicting resistance to treatment options.2
The 11th International Symposium on Minimal Residual Cancer was held this month and much of the conference was devoted to new minimally invasive methods for circulating tumor cell enrichment and or the analysis of circulating tumor DNA. Today’s clinical needs are to measure disease burden, track mutations over time, or to detect early resistance and all of these applications require extremely sensitive, robust assays.
SeraCare Customer Poster Talk Video with Data Presented by Asuragen
Next-generation sequencing (NGS) of liquid biopsies offers a minimally invasive alternative to solid tissue biopsies and a more holistic profile of intra- and inter-tumoral heterogeneity for therapy selection and disease monitoring.
Watch the video and download this free poster to learn:
Session Summary from Next Generation Dx Summit 2017
At the 2017 Next Generation Dx Summit in Washington, DC, our CSO, Russell Garlick, PhD, presented a workshop on accelerating liquid biopsy assay development. He has worked closely with a variety of groups in the liquid biopsy space that are developing and validating circulating tumor DNA (ctDNA) assays. He highlighted some common challenges facing the field, and explained how SeraCare has been using these collaborations to develop QC tools specifically for ensuring the robustness of these cutting-edge tests.
Topics: ctDNA, circulating tumor DNA reference Materials, circulating cell-free DNA, biosynthetic reference materials, assay development, assay performance, liquid biopsy, 2017 Next Generation Dx Summit
SeraCare’s new Seraseq™ Circulating Tumor Reference Materials
Clinical genomics laboratories are increasingly looking to liquid biopsy cancer assays to complement their current solid tumor assays. Compared to their solid tumor assay counterparts, circulating tumor DNA (ctDNA) assays offer a different set of challenges to consider for clinical labs. One of the most important of which, is to develop a set of reagents that are appropriately validated to determine the critical performance of the assay across many parameters. The ctDNA targets of liquid biopsy assays are typically at much lower allelic frequencies and require a robust and reproducibly designed assay to consistently detect these important variants.
A 0.1% measurement requires a reasonable amount of input material
The field of circulating tumor DNA analysis (ctDNA, also sometimes called in a larger context “liquid biopsy”) holds great promise for monitoring response to cancer treatment, assisting therapeutic choice, monitoring recurrence, and for pre-cancer screening. As such there is a great amount of assay development and ongoing clinical trials; at ClinicalTrials.gov searching for the term "Circulating DNA" you can find over 180 open clinical trials for a wide range of tumor types and interventions.
"The most effective ways to use QC data to monitor the health of your NGS assay."
Previously, we wrote about some of the Quality Control challenges that clinical laboratories performing Next Generation Sequencing (NGS) face towards ensuring their assays are safe and effective for guiding medical management decisions. Reliable access to high quality reference materials is necessary to help overcome these challenges; however, it is not sufficient. Insights that reference materials provide into the health of an NGS assay are only as good as laboratories’ ability to use their QC data effectively.
With limited time and resources to collect, organize, access, and analyze QC metrics, laboratories may frequently rely on reference materials as binary indicators of Pass/Fail: As long as the expected endpoint results are obtained, an assay is considered to be performing well. The drawback of this approach is that it is reactive, rather than proactive: A sufficient number of failures must occur within a given timeframe before a troubleshooting investigation is performed. By the time a problem is recognized, resources have been wasted and turnaround times (TAT) delayed; in some cases, fidelity of patient results may even have been put at risk. Additional time and costs are then incurred as the investigation proceeds.
Specimen analysis by NGS yields a wealth of information in addition to endpoint variant calls that is indicative of assay performance. Data such as nucleic acid quantity and quality at different steps throughout the workflow (PDF) and sequencing library characteristics are generated every time a reference material is tested. However, these data must be carefully tracked and trended to allow use as highly informative QC parameters. For clinical laboratories whose primary focus is on patient testing and reporting, granular QC metrics may not be captured and reviewed as part of routine test monitoring.
Non-invasive prenatal screening (NIPS) is currently offered in over 80 countries, covering over 80 million annual births, with an estimated volume of over one million screening tests performed annually. First offered in 2011, there has been rapid adoption of these genomic tests in the marketplace.
Important information for assay development and review by the FDA
The presentations during the FDA-AACR Liquid Biopsies in Oncology Drug and Device Development Workshop on July 19, 2016 included several important pieces of information that will likely guide the development of assays and their review by the FDA.
Diagnosing inherited disease, processing FFPE samples, state-of-the-art oncology in North Carolina, and developments in circulating tumor DNA technology
We are living through a time of rapid change in the clinical genetics laboratory, though at times it may appear that change doesn’t occur fast enough given the challenges within the existing healthcare system. At the recent Molecular Medicine Tri-Conference held in San Francisco March 7 through 11 2016, here are a few summary highlights of the conference.