Importantly, the majority of cancer samples analyzed were early stage cancers that were amenable to surgical resection, "a very important characteristic of this test because if you are just looking at late stage disease, obviously the test would not be nearly as helpful," Velculescu observed.
Because the genome-wide fragmentation patterns also reveal differences associated with specific tissues, fragmentation patterns can also indicate the source of that cancer such as the breast, colon, or lung.
For example, in the current analyses, DELFI was found to be 61% to 75% accurate in identifying the tissue of origin of the cfDNA, the team reports.
"What this means practically is that when you get a test like this in the future, you'll first get a result that says it's a positive test — it's a cancer signal — but then it's very important to know where the cancer is coming from because that will affect how you treat the patient," Velculescu said.
"So one of the benefits of this test is that it also tells you in a high fraction of cases where the tumor appears to be coming from and then that can help focus subsequent diagnostic tests and ultimately interventions," he added.
Velculescu indicated that their international research team is in the process of scaling up their analyses and they hope to study the performance of DELFI in many more thousands of individuals.
However, they are already "very encouraged" by the potential of this new technology because it looks at a completely independent set of DNA characteristics than those that have proven extremely challenging to the research community over the years.
Most immediately, Velculescu envisions DELFI being used in a high-risk patient population such as smokers or patients with a hereditary predisposition to cancer where a test specificity of 98% would still prove to be useful for those at high risk for cancer.
On the other hand, the test should not prove to be that costly, he added, as it is very easy to administer and needs only currently available, inexpensive laboratory methods to deliver results.
"As such, we expect DELFI will be more cost-effective than other cancer tests," Velculescu opined.
Holy Grail of Cancer Research
Asked by Medscape Medical News to comment on the findings, Daniel Hayes, MD, Stuart B. Padnos professor of breast cancer research, University of Michigan Rogel Cancer Center in Ann Arbor, noted that one of the holy grails of cancer research is finding a meaningful and accurate method of screening to detect cancers that might be more effectively treated early rather than late.
"This objective is a huge undertaking, with many obstacles, which is why there are so few really established screening strategies — arguably imaging for breast cancer, PAP smears for cervical cancer, and colonic visualization (for example, colonoscopy) for colon cancer," he elaborated in an email.
On the other hand, the prostate-specific antigen (PSA) story for prostate canceris a sobering example of screening on steroids, leading to over-diagnosis and unnecessary treatment, as Hayes pointed out.
Nevertheless, a circulating biomarker that is an effective screening strategy would be a very welcome addition to the field of oncology.
"The current study is, as the authors note, a 'proof of concept' investigation that does, apparently, work in a case-control design," as Hayes suggested.
"And without that success, there would be no reason to even consider moving forward, and I applaud Velculescu and colleagues for making this progress," he added.
However, the real proof of true clinical utility will still require a prospective trial involving many patients in which the assay is performed on participants who walk in the door with no prior diagnosis of cancer to see if they can separate out those who have cancer versus those who do not.
"Whether finding a 'positive' test [on this assay] results in treatment that improves overall, or cancer-specific, survival, or at least decreases the odds of long-term distant metastases is even more important," Hayes noted.
"But without [such a trial], the assay cannot be applied to guiding patient care, since it would not have clinical utility, although I am sure we all look anxiously for such data," he concluded.
Velculescu is a founder and shareholder of Delfi Diagnostics and Personal Genome Diagnostics, and a member of their scientific advisory boards. He has also been an advisor to Daiichi Sankyo, Janssen Diagnostics, Ignyta, and Takeda. Hayes owns stock or has other ownership interests in Oncimmune and InBiomotion and has served as a consultant or advisor to Cepheid. He has also received research funding, mostly for his institution, from AstraZeneca, Puma Biotechnology, Pfizer, Eli Lilly, Merrimack Pharmaceuticals, Parexel, and Menarini Silicon Biosystems (Veridex/Johnson & Johnson). He holds a number of patents and receives royalties for some of them.
Nature. Published online May 29, 2019. Abstract
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