This story has been updated to include comments from Diana Morlote of the University of Alabama-Birmingham.
NEW YORK – Aided by new technologies, cancer genetic testing labs are able to provide results from oncology panels faster than ever before, but the impact of lowered turnaround times on patient outcomes has yet to be determined.
Recent papers providing early data generated on Thermo Fisher Scientific's IonTorrent Genexus integrated sequencing platform suggested turnaround times of a day or less for cancer panels with dozens of targets.
Last month, researchers from France led by Paul Hofman of Nice University Hospital (CHU) published a retrospective study on the use of Thermo Fisher's Oncomine Precision Assay on the Genexus for gene fusion detections in nonsquamous, non-small cell lung cancer. The researchers also reported results for rapid multiplex RT-PCR testing on the Biocartis Idylla platform. They reported turnaround times as fast as 24 hours for sequencing and about three hours for PCR. Sequencing accuracy was 93.1 percent (92.3 percent for PCR), with "excellent" detection of ROS1, MET exon 14 skipping, and RET gene fusions. ALK fusion detection with sequencing was 88 percent.
In December, researchers from University of Pennsylvania Perelman School of Medicine led by Kojo Elenitoba-Johnson, now at Memorial Sloan Kettering Cancer Center, published a study in the Journal of Molecular Diagnostics on the use of the Oncomine Myeloid GX assay on the Genexus in patients with acute myeloid leukemia (AML). They also reported turnaround times of about 24 hours. Their panel detected 100 percent of DNA and RNA control variants; for patient samples, they detected 82 of 107 DNA variants and all 19 RNA gene fusions, for an 80 percent overall detection rate.
Both groups suggested that rapid return of results could have clinical implications. "It can mean the difference between a patient being put on a targeted therapy versus a standard first-line treatment, which may be less effective for their case," Elenitoba-Johnson said in an email. "Due to the urgency to put patients with advanced cancers on a treatment right away, long turnaround times for genetic testing results leave clinicians unable to make an informed decision on targeted therapies without the results in hand."
"Lung cancer is an aggressive disease," Hofman said in an email, noting that in advanced stages, results for potential genomic alterations in genes such as EGF, ALK, and KRAS must be obtained within 10 days. NGS testing can provide data on many gene alterations, but isn't always fast, his team noted in the paper. Rapid results can be obtained with single-gene tests and more traditional pathology methods but are limited by the sample material available and the growing number of tests called for by treatment guidelines.
At University of Alabama-Birmingham Medicine, some oncologists use the Genexus' fast turnaround time to provide treatment options for AML patients with a TP53 mutation. "If they have a TP53 mutation, this means prognosis is very bad and remission will likely not be reached despite aggressive management," Diana Morlote, a pathologist at UAB, said in an email. These patients are then given the choice to undergo less aggressive therapy to manage their disease with fewer side effects. "This decision needs to be made quickly, within five days from diagnosis," she said.
Given the nascence of rapid cancer testing — the Genexus was only launched in 2019 — actual data on patient outcomes is nearly non-existent. "It's human nature to want things as soon as possible, as long as the technology allows," said Yassmine Akkari, director of laboratory services at Nationwide Children's Hospital. For some diseases, such as the acute promyelocytic leukemia (APL) subtype, prompt treatment is known to be critical to patient survival. However, "these are special examples," she said. Akkari was not involved in the JMD study but noted that she considers Elenitoba-Johnson a friend.
"There probably are a lot of good things about doing it faster," Akkari said. "But we need to be cognizant of the sensitivity of an assay and whether it improves outcomes. What we need to ask ourselves is, 'What do you lose by doing it more rapidly?' I think that needs a little bit more study."
In the AML study, the Thermo Fisher platform missed several calls, including 15 DNA variants that were detected but not reported by the on-board bioinformatics pipeline and a missed FLT3 variant that would have resulted in "the inappropriate withholding of anti-FLT3 therapy," according to the authors.
Missing the FLT3 variant could be problematic, Akkari said, but not a dealbreaker. "Very few testing methods are absolutely 100 percent." These instances are a good reminder of the importance of validation testing, she said. If any systemic weaknesses are present, then they can be caught with reflex testing, she added.
One-day turnaround times require a certain level of sample throughput, the CHU researchers noted. Such testing "would not be cost-efficient in centers with lower throughput," they wrote. The Oncomine Myeloid GX assay has a list price of $15,250 for 32 reactions while the Oncomine Precision assay is $6,170 for 32 reactions.
As rapid whole-genome sequencing for patients in neonatal intensive care units has produced loads of data suggesting better patient outcomes and cost savings from fast turnaround times, similar testing strategies in cancer are on people's minds. Akkari is programming chair for the Association for Molecular Pathology's 2023 annual meeting, and the topic has come up in planning. It's too early to say whether it might feature in a session, she said, but with proof-of-principle studies completed, outcomes studies may not be far off.
Also, as AML care becomes a fully-fledged precision medicine discipline, use of all-inclusive panels like those run on the Genexus will likely grow. "There is no generic treatment anymore," Akkari said. "Everyone now takes into consideration a genomic rearrangement, unless you cannot find it. Every patient is going to get one test or another to find them."