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Symbiodx Launches NGS-based Cancer Panel; Inherited Cancer Test in Works

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NEW YORK (GenomeWeb) – Symbiodx, a Seattle-based joint venture between CellNetix and Pathology Associates Medical Laboratory (PAML), has launched a 68-gene cancer panel with plans to launch an inherited cancer panel in early 2015.

In February, the medical reference laboratory PAML bought part of CellNetix and the two companies formed Symbiodx. Anna Berry, the director of molecular pathology at Symbiodx, told Clinical Sequencing News that Symbiodx was formed to capitalize on the strength of PAML, which does clinical pathology services throughout the US, and CellNetix, which is a regional group of 50 pathologists, all of whom have subspecialty training. Symbiodx does all the esoteric testing, including FISH, immunohistochemistry, cytogenetics, and molecular testing, she said.

Initially, its molecular testing started small, with FISH-based KRAS, BRAF, and EGFR tests, Berry said. As volumes grew, "it became clear that in order for us to maintain the level of service we had historically, and to move forward, we really needed to do a cancer panel and we really needed to do next-gen sequencing," Berry said.

Symbiodx developed its cancer panel in conjunction with oncologists at the Swedish Cancer Institute, a network of cancer care centers in the greater Seattle area. Danbin Xu, technical director of molecular pathology at CellNetix, led the development of the panel.

The team used the list of genes that are included on commercial panels offered by Illumina and Thermo Fisher as a starting point, said Berry. For many of the genes, they expanded coverage to include the entire coding sequence for genes like EGFR, KRAS, and BRAF. For other genes that don't have a well-defined hotspot, the team expanded coverage beyond what the commercial kits cover, she said, and they also included genes relevant for hematological malignancies and a few pharmacogenomics genes.

The final custom developed panel includes 68 genes. It runs on Illumina's MiSeq system out of a CLIA-certified and CAP-accredited laboratory, has a turnaround time of 14 days, and a list price of $2,400, although Berry said that discounts are offered for patients without insurance or who are self-insured.

Oncologists order the test primarily for patients who have failed first-line treatment. Berry said that some oncologists, particularly those treating lung cancer patients, will order the test on initial diagnosis, and she said she anticipates that more and more oncologists will begin ordering the test right away.

Currently, she said that such NGS-based molecular tests are more likely to be reimbursed for patients who have failed the first line of standard therapy. But going forward, she anticipated that highly targeted assays especially, would increasingly be ordered for patients at initial diagnosis, since such assays strike a good balance between cost efficiency compared to single-gene tests and the challenges of dealing with variants of unknown significance in more comprehensive tests.

She said it was still too early to comment on the reimbursement situation, but thinks that NGS-based targeted tests will eventually be regularly reimbursed. "It makes logical sense to get all the markers you need up front with less cost and less DNA" than single-gene testing, she said.

The company has partnered with CollabRx for interpretation and also has its own rules-based engine that it uses to evaluate each test. The final report is manually reviewed and signed off on by either Berry or one of two other trained pathologists.

The report is delivered as a PDF that has links to the suggested clinical trials and the references. In addition, Symbiodx has a web portal through which clinicians can order the test, check on the status of the case, and review the final report.

Currently, Symbiodx receives about 10 to 15 cases per week, but Berry said volumes will likely ramp up to 50 cases per week this fall and 100 cases per week by the end of the year. She added that Symbiodx will likely purchase a HiSeq system to handle the increased volume load.

In addition, Symbiodx has other cancer tests in the works. Berry said that the team will likely develop some smaller panels. For instance, some of the gastrointestinal oncologists Symbiodx works with have requested RAS and BRAF testing only. Other smaller panels will likely be limited versions of the 68-gene panel, where some results are masked, she said. In early 2015, the firm plans to launch an inherited cancer panel. Also, it will revise its existing 68-gene panel every six to 12 months, she said.

Berry said that the revisions would not be huge changes. A few genes may be added, she said, in other cases coverage of some genes may be expanded, and in some cases, genes may even be removed. For instance, she said, the team would likely remove the gene HNF1A in the next iteration because it doesn't have a strong enough link to cancer to be actionable. The gene is associated with hepatic adenomas and "is not really relevant for most of our patients," Berry said.

While some companies and academic centers have moved to offer large panels with hundreds of genes and even whole-exome tests, Berry said that Symbiodx does not have immediate plans to go in that direction, primarily because of the bioinformatics and interpretation challenges with the large numbers of variants of unknown significance that those tests identify. "In some clinical circumstances those tests are useful and appropriate, but not in routine testing, which is the arena that we see ourselves in right now," Berry said. "But, I certainly think the field is moving in that direction and we'll move there too when the time is appropriate."