This article previously described the ICG100 Onco Focus Panel as a next-generation sequencing test based on an Intermountain press release that erroneously described it as such. The panel uses Agena Bioscience's MassARRAY system, and this article has been updated to reflect that.
NEW YORK (GenomeWeb) – A newly launched five-oncogene, mass spectrometry-based test has allowed Intermountain Healthcare to analyze cancer patients with limited tissue samples hoping to receive personalized treatment, while also helping the healthcare system to significantly lower its test rejection rate.
Mutations in the five genes gauged by Intermountain's ICG100 Onco Focus Panel ― KRAS, BRAF, NRAS, EGFR, and KIT ― are more likely to show up in lung, melanoma, and colon cancer patients and can be targeted by marketed drugs. These aspects, and the fact that the smaller panel, which utilizes Agena Bioscience's MassARRAY system, is cheaper to perform than more comprehensive next-generation sequencing-based testing that Intermountain offers, makes it more likely to be reimbursed by insurers, providers are hoping.
Four years ago, Intermountain began offering Stage IV metastatic cancer patients the chance to receive genomic profiling on a 100-gene panel. The Salt Lake City-headquartered healthcare system recently expanded the panel to include 162 genes associated with cancer pathways. The ICG100 Comprehensive Cancer Panel gauges around 4,000 SNPs, large and small indels, and copy number variations, but requires about 150 nanograms of DNA, according to David Loughmiller, core lab manager at Intermountain Precision Genomics, which provides genomic sequencing services for Intermountain Healthcare.
By comparison, the smaller panel gauges around 160 SNPs, insertions, and deletions, but not copy number variations. The ICG100 Onco Focus Panel requires 20 nanograms of DNA, or between 5,000 and 8,000 cells, of which 40 percent must be malignant. “We were receiving from interventional radiology needle biopsies with a very small amount of sample, and we wanted the ability to decrease the quantity of insufficient samples that we were seeing for our larger panel,” Loughmiller said.
With the larger panel, around 18 percent of the patients that requested testing had insufficient material analysis. Using the edited panel, the lab was able to reduce the number of tests rejected due to insufficient samples by 80 percent, and now, Loughmiller estimated that only 3.6 percent of tests are rejected.
“That was a huge component of it for us, to be able to have something we can give to the patient” with a small amount of sample for analysis, he said. “Even if we couldn't give the larger panel, we would still be able to give some specific information for those specific genes we were looking at.”
Insufficient samples are a persistent problem in cancer genomic profiling. “Nationwide I've seen some studies that show that with needle biopsies particularly, most labs are seeing about a 20 percent to 30 percent rejection rate because there isn't enough material to perform any of the sequencing on it,” he said.
Sampling challenges have slowed enrollment in studies investigating whether genomic profiling improves outcomes. These studies are being closely followed as healthcare providers decide how often to order genomic profiling for their cancer patients, and payors decide the circumstances under which to pay for testing.
For example, the NCI-MATCH study was initially slow to “match” patients to biomarker-guided treatment arms, partly because of sample quality. The study uses Thermo Fisher Scientific's 143-gene OncoMine assay and requires 20 nanograms of genomic DNA and 10 nanograms of RNA, according to a recently published validation of the platform. The test is able to gauge hotpots, single-nucleotide variations, indels, copy number variations, and gene fusions.
A year ago, NCI-MATCH investigators reported that the labs involved in the study were analyzing 87 percent of cases, but 13 percent were not being analyzed due to insufficient amounts DNA or RNA, or too few cancer cells in the sample.
Since then, researchers involved in the study have made some changes, such as mandating needle aspiration in all cases, in an effort to improve testing rates. According to more recent data presented by NCI-MATCH's primary investigators, the labs analyzing samples for this study are now able to complete tumor testing in 93 percent of cases, which is above the industry's 80 percent test completion rate.
The core lab at Intermountain is also continuing to make improvements to its comprehensive and focused panels so that they can lower rejection rates. Loughmiller noted that his lab has been able to reduce the input volume for the ICG100 Comprehensive Cancer Panel from 150 nanograms of DNA to 100 nanograms. And while the ICG100 Onco Focus Panel requires 20 nanograms of DNA, of which 40 percent currently must be DNA from tumor cells, the lab is working to bring that down to 20 percent malignant cells, in line with recommendations from groups like the American Society of Clinical Oncology and others.
Of course, there will be some key biomarkers that could guide personalized treatment strategies for cancer patients, for example, such as ALK and ROS1 translocations in lung cancer, that the smaller panel can't assess. These two markers, along with PD-L1 expression for guiding immunotherapy, are performed using IHC. For patients with small amounts of tissue available for genomic profiling, the ICG100 Onco Focus Panel is now a viable option, and depending on how much tissue was left over, there may or may not be opportunity for additional biomarker testing.
Having to analyze fewer genes, Intermountain is able to return results in two days, whereas the 162-gene panel and other larger NGS panels have a turnaround time of two weeks. “That was another attractive piece,” Loughmiller said.
While he didn't discuss the price of the new test, he estimated the cost of running the smaller assay at about one-fifth of the larger panel. “We would anticipate that Medicare would reimburse at a better rate, not necessarily at a higher dollar volume, but at a better rate than what we'd see with the larger panel,” he said.
Insurers have balked at paying for NGS testing, because they consider most of the genes on the panels as lacking in clinical utility evidence and, therefore, as being investigational. Analysis from Diaceutics, a medical technologies firm that has been tracking diagnostic trends using data from 250 labs and claims, suggests that as little as 4 percent of next-generation sequencing tests are currently being reimbursed, CEO Peter Keeling estimated during a recent interview.
According to Loughmiller, Intermountain hasn't had “as much of a problem getting reimbursed as some institutions" for genomic profiling tests, though he noted “it still is a challenge with Medicare.”
Medicare contractor Palmetto last year issued a final local coverage determination for comprehensive genomic profiling in non-small cell lung cancer, and draft LCDs for comprehensive genomic profiling in metastatic colorectal cancer, metastatic melanoma, and advanced primary peritoneal, fallopian tube, and ovarian cancer.
“Just having to go through the technical assessment with Palmetto is not a trivial process,” said Loughmiller. His lab is currently taking ICG100 Comprehensive Cancer Panel and ICG100 Onco Focus Panel though Palmetto's technical assessment process, through which molecular tests can gain coverage if they meet certain criteria for analytical and clinical validity, as well as clinical utility.