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Switching from SOLiD to PGM, Fox Chase Adopts Targeted Sequencing for Cancer Patients


By Monica Heger

This article was originally published Dec. 19.

The Fox Chase
Cancer Center, which had planned to begin offering exome and transcriptome sequencing for cancer patients on Life Technologies' SOLiD this fall, has decided to forgo those plans in favor of a more targeted approach on the company's Ion Torrent PGM.

The center's Cancer Genome Institute will now offer targeted sequencing on Ion's AmpliSeq Cancer Panel via its CLIA-certified laboratory, Jeff Boyd, executive director of Fox Chase's Cancer Genome Institute, told Clinical Sequencing News this week.

The AmpliSeq Cancer Panel, which LifeTech launched in October (CSN 10/12/2011), covers 190 amplicons in 46 cancer genes. The genes were chosen based on input from cancer researchers, although not from the Fox Chase Cancer Center. The panel covers genes that are commonly somatically mutated, as well as genes known to be responsible for inherited forms of the disease.

While Fox Chase's cancer sequencing service was originally slated to launch this fall on the SOLiD (CSN 6/15/2011), Boyd said that because the cancer center decided to switch strategies, it will be another "several months" before the Ion PGM machines and AmpliSeq Cancer Panel are validated in the center's CLIA lab and can be offered to patients.

The center no longer has its three SOLiD instruments, and is instead equipped with two PGMs. Boyd said the lab would likely acquire more PGMs as it scales up. He initially expects testing volumes in the "low hundreds of patients per quarter."

Boyd said the team is targeting a two-week turnaround time from the biopsy until results are returned to the physician.

He said that the team decided to switch over to the PGM and use a more targeted approach because from a "patient and clinical perspective, the PGM is really the way to go in terms of cost and efficiencies."

The genes included in the panel can be targeted by either drugs with US Food and Drug Administration approval, off-label drugs, or an existing clinical trial, Boyd said.

"In a clinical context … there's not a whole lot of extra information in the whole exome in terms of known drug targets that we can't glean from the AmpliSeq panel," he added.

Originally, the team had planned to offer whole-exome and whole-transcriptome sequencing. While Boyd said that those approaches are still relevant in a research setting, "from a clinical context, I think that it's too much in terms of having a reasonable turnaround time and having a reasonable cost that may or may not be reimbursable in the near future."

He said that when the service is launched, the team will be using Ion Torrent's 318 chip and 200-base reads. One patient sample will be run per chip, which will allow the team to include two samples from the patient's tumor, two normal samples, plus positive and negative controls.

Including replicate samples and controls, "we'll have adequate quality control built in so we won't have to validate any alterations we find using another technology, like Sanger sequencing or real-time PCR."

While the lab has not decided on a cost for the test, Boyd said that internal costs, not including personnel and overhead, are around $1,500, so he anticipated a final cost in the range of $2,000 to $3,000.

Initially, patients would pay out of pocket, but the goal is to eventually negotiate reimbursement with payors. Boyd said he expects that as the multi-gene panel test approaches the same cost as a reimbursable single-gene test, it will be easier to make a case for reimbursement.

"That will be a big factor in terms of tipping the reimbursement scale in our favor," Boyd said.

Both the Centers for Medicare and Medicaid and the FDA are aware of next-generation sequencing and are beginning to think about how to address its use in genetic testing, he added.

A Growing Field

The Fox Chase test will be one of the first next-gen sequencing-based cancer tests offered in a CLIA setting, but the field is quickly growing more crowded. For example, Washington University's School of Medicine recently launched a 28-gene cancer test in its CLIA lab on Illumina's HiSeq (CSN 11/30/2011).

Baylor College's Genetics Laboratory is also planning a cancer test using Ion's AmpliSeq Cancer Panel. However, it has said that it will be for research use only, despite being run in its CLIA lab (CSN 11/30/2011).

The Children's Hospital of Los Angeles and the University of Pennsylvania both plan offer tests for retinoblastoma, a rare childhood cancer, on the PGM in 2012, from their respective CLIA labs (CSN 10/26/2011).

Meantime, the University of Michigan is taking a more comprehensive approach to clinical cancer sequencing through its Mi-OncoSeq program, offering whole-transcriptome, whole-exome, and low-pass whole-genome sequencing on the HiSeq.

Currently, the sequencing for Mi-OncoSeq is performed in a research lab and results are validated in a CLIA setting before they are reported to the physician. U of Michigan is pursuing CLIA validation for the next-gen protocol, however.

While targeted panels may offer actionable information quicker and cheaper, Arul Chinnaiyan, who heads the Mi-OncoSeq program, has said that his team has uncovered critical, actionable data from the transcriptome sequencing that would have been missed in a targeted approach (CSN 12/7/2011).

Additionally, researchers from the Translational Genomics Institute found in a recent clinical trial for breast cancer that some information identified via sequencing that led to a treatment decision may not have been found in a targeted approach (CSN 12/14/2011).

Nevertheless, Boyd said the Fox Chase team decided to make the switch from exomes and transcriptomes to a targeted approach because it was more cost effective and quicker than those options.

For instance, in the TGen study, which used Life Tech's SOLiD for the sequencing, turnaround time was around five to six weeks, while Michigan's turnaround time for its Mi-OncoSeq protocol is three to four weeks.

Boyd said that on the PGM, two weeks is a conservative estimate and that results could likely be returned even quicker. Additionally, he anticipates that the team will add additional genes to its panel as they become validated and as the throughput of the PGM increases.

He did not rule out eventually offering whole-exome sequencing on the PGM as throughput increases and the price of sequencing drops.

Have topics you'd like to see covered by Clinical Sequencing News? Contact the editor at Monica Heger.