Liquid Biopsies Sent To Different Labs May Yield Different Results Interview with:
Gonzalo Torga, MD
Urology Department
Johns Hopkins Hospital
Baltimore, MD 21287 What is the background for this study? What are the main findings?

Response: Liquid biopsy is a new and noninvasive alternative to tumor tissue sequencing, and it is intended to specifically detect and sequence tumor DNA circulating in patients’ blood. The results are used to help guide oncologists to tailor the best treatment for patients at each point of their disease. Our research was initially aimed at finding the best commercial lab to test samples from metastatic prostate cancer patients. We wanted to make the best choice for our patients, so we started submitting the samples to both places at the same time to compare results. However, we found significant disparities in the results from identical patient samples submitted to two different commercial liquid biopsy providers, and we believed it would be important to share them with the oncology community.

The two liquid biopsy panels compared were the Guardant360, from Guardant Health, Inc., which sequenced at least part of the coding sequences of 73 genes; and the PlasmaSELECT panel from Personal Genome Diagnostics, which sequenced coding segments of 64 genes.  Both laboratories were licensed by Clinical Laboratory Improvement Amendments (CLIA) and accredited by the College of American Pathologists (CAP), and report having high sensitivity (in this case, the ability to correctly identify mutations when they occur) and high specificity (the ability to correctly report as negative when those mutations are not present). The two companies differ in which genes, and regions within each gene, are covered. Just 25 of the 40 patients in the study had at least one genetic mutation reported within the overlapping genetic sequences covered by both companies.

Even when the companies were analyzing DNA from the same blood drawn, their results rarely matched each other. When comparing results within the overlapping genetic sequences, the results from both companies completely matched for all the mutations reported in only 7.5 percent (3 of 40 patients) of cases. In 15 percent of the patients (6 of 40), both companies’ results matched for at least one of the reported mutations. In 40 percent (16 of 40) of the patients, no mutations reported that were potentially covered by both panels were detected by both companies. What should clinicians and patients take away from your report?

Response: Oncologists should be become aware of these inconsistencies so that they do not blindly trust liquid biopsy results. Patients may respond differently to cancer drugs depending on what kinds of gene mutations they have in their tumors. Oncologists use the results of a liquid biopsy to see if a patient is responding to treatment and to monitor tumors to see if they are progressing and may require a new or extra therapy. The results raise the possibility that cancer patients could be prescribed different treatments depending on which commercial provider is used for liquid biopsy. They may also use the results to select patients for clinical trials, if a specific mutation is found in their tumor’s DNA. What recommendations do you have for future research as a result of this study?

Response: Liquid biopsy is a promising technology, with an exceptional potential to impact our ability to treat patients, but it is a new technology that may need more time and experience to improve. We can’t tell from these results which laboratory’s panel is better, but we can say that certification for these laboratories must improve. Is there anything else you would like to add?

Response: First and foremost, we would like to express our gratitude to our patients. Also, we would like to thank Personal Genome Diagnostics and Guardant Health for their help confirming coverage for each mutation in their next generation sequencing (NGS) panels. All other authors report no disclosures. All authors approved the final manuscript. Thank you for your contribution to the community.


Gonzalo Torga, Kenneth J. Pienta. Patient-Paired Sample Congruence Between 2 Commercial Liquid Biopsy Tests. JAMA Oncol. Published online December 14, 2017. doi:10.1001/jamaoncol.2017.4027

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Last Updated on December 16, 2017 by Marie Benz MD FAAD