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Liquid biopsy platforms yield substantially different results
Two commercial liquid biopsy platforms that evaluated tumor samples from the same patient population yielded significantly different results, according to study findings.
Gonzalo Torga, MD, postdoctoral research fellow at Brady Urological Institute at Johns Hopkins, and Kenneth Pienta, MD, director of research and prostate cancer researcher at Brady Urological Institute and medical oncologist at Johns Hopkins Kimmel Cancer Center, sent identical samples from 40 men with prostate cancer for analysis by the Guardant360 (Guardant Health) and PlasmaSELECT (Personal Genome Diagnostics) platforms.
Guardant360 sequenced at least part of the coding sequences of 73 genes, and PlasmaSELECT sequenced segments of 64 genes.
Results showed only 25 (62.5%) of 40 patients had at least one genetic mutation reported within the overlapping sequences covered by both companies.
When researchers compared results from overlapping genetic sequences, they determined the results from both platforms matched completely for all mutations in only three of 40 patients (7.5%). Both platforms’ results matched for at least one reported mutation for six (15%) of the 40 patients. In 40% of cases, no mutations that could have been covered by both panels were detected by both platforms.
“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,” Torga said in a press release.
“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,” he added. “We can't tell from these studies which laboratory's panel is better, but we can say that certification for these laboratories must improve.”
HemOnc Today spoke with Pienta and Torga about the clinical utility of liquid biopsies, the rationale for this study and the potential implications of their findings.
Question: What prompted this study?
Answer: Cell-free DNA (cfDNA) next-generation sequencing was the first multiplex-capable liquid biopsy technology to be available for the clinical setting. A few months after both panels became commercially available, we started to submit patient-paired samples from the same blood drawn to both companies. At that time, given the technology was recently introduced, there were no sufficient clinical data available for us to determine which test would perform better. The initial intention was to find the best commercial lab to test samples for metastatic prostate cancer patients.
Q: What advantages do liquid biopsy approaches offer?
A: Conventional biopsy methods are technically challenging and invasive, making multiple sampling problematic. Multiplexed cfDNA next-generation sequencing-based liquid biopsies are noninvasive and, therefore, suitable for real-time monitoring of disease by serial sampling, allowing physicians to follow clonal evolution and detect de novo mutations. This potentially could potentially enable oncologists to tailor cancer therapy over the course of disease — a true precision medicine paradigm.
Q: Are there any potential disadvantages or safety concerns?
A: We believe liquid biopsy has great potential to identify specific known mutations that are associated with specific tumors — for example, ALK in non-small cell lung cancer. For mutation discovery overall, tissue-based next-generation sequencing remains the gold standard. Patients and physicians seeking actionable information about the mutations in a tumor still need to rely on a tissue biopsy. Liquid biopsy tests need to be ordered in the context of the patient, the type of cancer and their disease burden — issues that are not well explained by the companies that offer the testing.
Q: How might this approach alter therapeutic decision-making, and what impact could the discordant results between platforms have on patient care?
A : Patients may respond differently to cancer drugs depending on what kinds of gene mutations they have in their tumors. Ideally, oncologists could 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 of our study raise the possibility that patients with cancer could be prescribed different treatments depending on which commercial provider is used for liquid biopsy. Moreover, physicians may also be using the liquid biopsy results to select patients for clinical trials, if a specific cancer-related mutation is found in their cfDNA.
Q: What must be evaluated or confirmed in future studies?
A: We would like to further investigate the clinical utility of cfDNA-based liquid biopsy longitudinally in our cohort, and repeat cfDNA testing to the same patients to determine which provider performs better in the clinical setting of metastatic prostate cancer. – by Rob Volansky
Reference:
Torga G and Pienta KJ. JAMA Oncol. 2017;doi:10.1001/jamaoncol.2017.4027.
For more information:
Kenneth J. Pienta, MD, and Gonzalo Torga, MD, can be reached at The Johns Hopkins Hospital, Department of Urology, 600 N Wolfe St., Marburg 113, Baltimore, MD 21287; email: gtorga@jhmi.edu.
Disclosures: The authors report no relevant financial disclosures. The PlasmaSELECT test used in the study is owned by Personal Genome Diagnostics. The Johns Hopkins University has licensed technologies to Personal Genome Diagnostics and, as a result, has a financial interest in the company. This arrangement has been reviewed and approved by the Johns Hopkins University in accordance with its conflict-of-interest policies.