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Attendees of Monday’s launch of Argos, the self-service user interface designed to allow Fred Hutch/University of Washington Cancer Consortium members to access and analyze data being pumped into the Hutch Integrated Data Repository and Archive, or HIDRA, got a peek at some of the application’s many potential uses.
Argos, built in partnership with LabKey Software, is “designed to get you the quickest, easiest stuff you feel should be at your fingertips,” said Biomedical Informatics Director Paul Fearn, who has helped spearhead the HIDRA project. Argos enables researchers to look at the most common research-related questions across a broad set of data, balanced with tight security controls, Fearn said.
“It puts power in the hands of the research community with no need for database knowledge,” said Sarah Ramsay, director of IT informatics at Fred Hutch.
Fearn and Ramsay demonstrated how Argos users can easily sort and compare patient information by various characteristics, such as cancer diagnosis and gender. This will help researchers, for example, estimate patient accrual to a given clinical trial based on historical information on Cancer Consortium patients who meet relevant criteria.
Researchers hoping to answer more in-depth questions by utilizing Cancer Consortium data in HIDRA can contact Center IT informatics for help, Ramsay said.
Argos is also designed to “play well with others,” Fearn said. Open source and built to industry standards to facilitate safe and easy sharing with other institutions, Argos was developed to foster collaboration and scientific inquiry far beyond the Consortium.
Currently, Argos serves the brain, thoracic and gastrointestinal cancer disease groups, but it will continue to expand until it serves all disease groups in the Consortium. The Argos team will be reaching out to each disease group to begin the process of customizing their views and access to data. Argos, in conjunction with the HIDRA core repository, which currently includes 335,000 patient records, will facilitate the Consortium’s goal of providing its researchers with access to one of the broadest and richest sets of clinical and molecular data available, Ramsay said.
For 15 years, doctors who care for patients with acute myeloid leukemia have been using standardized treatment guidelines and models for predicting outcomes that take into account specific genetic signposts, known as prognostic biomarkers. What those guidelines and models haven’t accounted for is the potential impact of the patient’s age on those biomarkers ― but a new Fred Hutch–led study suggests that they should.
Many of these prognostic biomarkers were identified and validated in studies of younger AML patients; however, many patients with AML are over the age of 65. This raises the question: Are these prognostic biomarkers still prognostic in older patients?
A study published online Feb. 23 in the Journal of Clinical Oncology by Drs. Fabiana Ostronoff and Derek Stirewalt, their colleagues in Fred Hutch’s Clinical Research Division and outside collaborators examined two of the most common genetic abnormalities in AML that are widely used, as per clinical guidelines, as prognostic biomarkers. The study built on previous research by Dr. Fred Appelbaum at Fred Hutch and other collaborators suggesting that some favorable prognostic factors in younger patients with AML might not be associated with favorable prognosis in older AML patients.
The researchers analyzed the prognostic significance of mutations in NPM1 and FLT3 in approximately 1,400 patients age 55 and older with AML who were treated with intensive chemotherapy with curative intent as part of trials through SWOG (formerly Southwest Oncology Group) and the United Kingdom’s National Cancer Research Institute/Medical Research Council. They found that, unlike younger patients, those over age 65 with NPM1 mutations did not have a favorable prognosis. In fact, most older patients with this mutation actually relapse and die of their disease within two years of diagnosis. These results call into question the use of current risk-stratification models and guidelines for older adults with AML.
Using the wrong prognostic criteria can have major consequences for patients, said Stirewalt, who has seen many older patients who quickly relapsed after their doctors gave them chemotherapy, rather than transplant, on the basis of a supposedly favorable genetic signature.
“If doctors realized it’s not favorable, they would be more likely to push the patients toward either clinical trials or perhaps early transplant, which may have more success than the standard therapy,” he said, referring to chemotherapy.
“We think there are probably other genetic abnormalities that haven’t been clearly identified or characterized as being prognostic in older adults, and it is these additional biomarkers driving some of the adverse biology in older adults with this disease,” Stirewalt said. He estimated that several more years of research will be needed to determine the most helpful prognostic predictors in older AML patients.
This result “highlights the fact that you probably cannot merely generalize the results from historic biomarker studies examining younger patients to older populations,” he said.