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Physicians' Plans to Implement NGS-based Tumor Tests Vary Widely, Study Finds

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Physician adoption of genomic tests to guide treatment of cancer patients may lag far behind the development of such tests, according to a new study.

Over the last several years, academic institutions and companies have launched a number of genomic-based tests, including many based on next-generation sequencing, to screen patients' tumors for alterations that point to targeted treatments or clinical trials.

Due to advances in technology and the falling prices of sequencing, targeted gene panels in particular, have become feasible to do in a clinically relevant time frame. But according to a recent study published in the Journal of Clinical Oncology, only a fraction of physicians intend to use such tests.

Researchers at Harvard Medical School and the Brigham and Women's Hospital surveyed 160 physicians at the Dana-Farber Cancer Institute, a tertiary-care National Cancer Institute-designated cancer center, about their plans for incorporating multiplex somatic genomic tests into their practice, as well as their attitudes about disclosing genomic information of uncertain significance and their genomic confidence.

Only 25 percent of physicians anticipated testing 90 percent or more of their patients and 18 percent of physicians said they would test 10 percent or less of their patients.

"Our ability to perform multiplex genomic testing is far outpacing physicians' intentions to perform them," Stacy Gray, an assistant professor of medicine at Harvard Medical School and lead author of the study, told Clinical Sequencing News. "The findings from the study really point to the fact that it is probably going to be a while before this kind of testing is routinely used in cancer care."

Dana-Farber offers genomic tumor testing for all patients under a research protocol, where consenting patients can receive actionable and potentially actionable results of the test. The protocol, dubbed Profile, was initially launched in 2011 and used a targeted mass spec-based technology called OncoMap to assess 41 genes, but recently transitioned to a targeted sequencing panel of 305 genes called OncoPanel. Testing is done at the Center for Advanced Molecular Diagnostics, a CLIA-certified laboratory at Brigham and Women's Hospital.

The researchers conducted the study just prior to Dana-Farber's switch to the NGS-based OncoPanel test, Gray said. And as part of the researchers' plans to follow up on the survey, they plan to ask the physicians how they are using the next-gen sequencing technology and see whether there are differences in attitudes toward that test. "It's both a different technology and a larger number of genes that are being queried," Gray said.

Gray said she was surprised by the amount of variation in the physicians' plans to use genomic testing, particularly since Dana-Farber has a protocol in place by which every patient can receive genomic testing.

She hypothesized that genomic testing may vary by cancer disease group or specialization. For instance, she said, genetic testing of lung cancer patients is not a new concept, so oncologists that treat lung cancer patients may have been among the group that anticipated testing most of their patients. On the other hand, "there are other types of diseases where genetic testing of the tumor isn't historically performed at all," such as for early-stage bladder cancer, Gray said.

Additionally, the researchers surveyed different types of physicians, including medical oncologists, radiation oncologists, and surgeons. Since genetic testing is not something that radiation oncologists do, Gray hypothesized that responses may have varied depending on the physician's specialty. Of the 160 physicians, 57 percent were medical oncologists, 29 percent were surgeons, and 14 percent were radiation oncologists.

Finally, the researchers found that physicians' confidence in their own genomic knowledge was a strong predictor of whether or not they planned to incorporate testing into patient care. Around 22 percent of physicians responded that they were not very confident or not at all confident in their knowledge of genomics, while 14 percent said they were not confident in their ability to explain genomics to their patients, and 26 percent said they were not confident in making treatment decisions based on genomic findings. Around 78 percent were somewhat confident or very confident in their knowledge of genomics.

The researchers found that medical oncologists, researchers, and physicians that already performed some level of genetic testing were more likely to feel confident about their own genomics knowledge.

The findings on genomic confidence raise the question as to whether and where more effort should be put into educating providers about genomics, Gray said.

The physicians also differed in their opinion on disclosing genomic results to patients. Somewhat surprisingly, more than 40 percent of physicians favored disclosing genomic findings of uncertain significance, while around 39 percent disagreed with a policy that would prohibit the return of uncertain findings. Nevertheless, 23 percent of physicians said they would only rarely or sometimes disclose genomic variants that were known to be clinically relevant, such as ones that have approved drugs associated with them.

Gray said that the researchers plan to follow up with the physicians to see whether or not their behavior matches their survey responses. "We want to go back and see how they are using genomic tests and whether or not the information they've gotten from the tests has been helpful in making decisions and treatment recommendations."

Another possible contributor to the wide variation around physicians' intentions to use genomic tests is the uncertainty around reimbursement and cost for such tests. Questions around reimbursement and cost were not included in the survey.

Gray said the follow-up survey should be completed within the next year and the researchers expect results by 2015.

How genomic testing will ultimately play out in the clinic for cancer patients is "one of the most interesting questions in oncology right now," Gray said. "It is a little bit unpredictable how physicians will use the information or if they will use information that is more uncertain in nature," she said. "And we also don't really have a good sense for who is going to adopt the technology quickly and who is going to wait and see."

Nevertheless, though, genomic testing firm Foundation Medicine has reported rising revenues for its FoundationOne test, which analyzes over 200 cancer-related genes for patients with solid tumors and its FoundationOne Heme test for blood-based cancers. This year, it expects to report between 22,000 and 25,000 tests, and in the fourth quarter of 2013, more than half of its tests were performed for clinical customers.

While Foundation Medicine is the only company that has reported results of its genomic tests, other companies also offer similar services and are making plans to expand. Caris Life Sciences offers an NGS assay based on Illumina's 48-gene TruSeq panel, as well as mRNA fragment analysis of the EGFR gene and immunohistochemistry assays to identify clinically relevant copy number alterations. Last year, the firm told CSN that it genomically profiles around 12,000 patient tumors per year.

However, Gray said that the survey suggests that there is significant room for growth of genomic testing in oncology. Right now, "it's not a standard of care," she said. Endorsement by professional organizations in guidelines for treating cancer patients could help spur increased uptake, she said.

"The ability to do comprehensive, complicated genomic testing is available now," she said. "But even at a major cancer center … a significant minority of providers lack confidence in their knowledge of genomics, their ability to explain genomic concepts to patients, and their ability to use genomic information to make treatment recommendations."