Expert: Circulating Tumor DNA Is A “Hidden Link” to Monitor Colorectal, Other Cancers

In an interview with Pharmacy Times at the American Society of Clinical Oncology (ASCO) 2022 Annual Meeting, Bruce Feinberg, DO, vice president and chief medical officer at Cardinal Health Specialty Solutions, discussed the use of circulating tumor DNA (ctDNA), its current use in colorectal cancer, and how it could be used in other cancers in the future.

What is circulating tumor DNA and how is it currently used in oncology?

Bruce Feinberg, DO: So, it's interesting that if we think back to the early years of cancer, the thought was that the cancer was a disease of an organ. It's a disease of the breast and so, as a result of that, the radical mastectomy removed the breast, the muscles underlying the breast, all the lymphatics of the breast area, all the blood vessels of the breast area. And those were radical surgeries with serious side effects and really disfiguring [to] the patient. As we learned that cancer cells are microscopic—thousands fit on the head of a pin—they get into the circulation and bloodstream before the tumors are big enough to be seen, we realized this is no longer really a disease of an organ, it's a disease of a cell. And those cells are then circulating, so we had to start implementing, we could use less surgery, but we had to give total body treatment in the form of adjuvant treatment, adjuvant chemotherapy—or adjuvant hormonal therapy in the case of breast—in order to try to destroy those cells, which did leak out into the circulation. Now, we've evolved beyond that to understand that it's all a genetics-based process in which an abnormal gene expression leads to the behavior of the cell, which then leads those cells leaking into the circulation before the tumors are big enough to be seen. So, this evolution over time has reframed our ability to understand and think about cancer treatment.

Well, we now understand that as those cells leak into the circulation, the cells themselves may not remain intact, but their DNA signatures will remain—the chemical of the DNA is still there. And so, cell free-circulating tumor DNA is this kind of hidden link to what's going on with the cancer. And it's a hidden link which gives us a sensitivity of understanding that is far greater than what we can get with imaging. With imaging, we're limited to a tumor size that's a centimeter, maybe as small as a half centimeter. With circulating tumor DNA, we're getting down to multiple exponential levels below that, and a way for us to really understand, at a sub microscopic level, how much cancer there may be in that patient's body. So, it's a really interesting tool.

It's been useful already in liquid tumors because that was the thinking that the cells are already living in the blood, there should be elements of the DNA still there. But we realize it's also present in solid tumors. And I can envision a day, and it could be in 10 years, that we're not doing CT scans every 3 months, but we're drawing a blood sample instead, to see if circulating tumor DNA is still present in the body, rather than trying to look at a CT scan to see if there's still a large cluster of cancer cells.

How is ctDNA specifically useful in colorectal cancer?

Bruce Feinberg, DO: So, as far as the solid tumors in which circulating tumor cell free DNA has been found and has been studied, there's a handful of them that are starting to emerge where the studies have been mature, refined, large enough to provide evidence on which to grow this theory that we can move beyond the limits of traditional imaging to a different way of assessing the tumor persistence in the body. And colorectal cancer is one of those tumors that's been studied heavily, in which there's published data. And because there is now strong evidence, the question for us as researchers was, now that there is evidence, to what extent is that evidence being recognized? And is it valued to the extent that it's being used? And so that was the reason for the research.

How was your research conducted and what was its goal?

Bruce Feinberg, DO: Most of our work is by reaching out directly to prescribing physicians, treating physicians. So much of observational data historically has focused on using claims data, which tells you what was done and when it was done, with the argument being in a fee-for-service system, everything that's done will be charged for, and so there would be a billing record. And that was the basis as we moved into electronic health records. The idea is everything that's in the health record could then be another source of data. The problem in health records is much of what's in there is not structured, meaning that it's just an open narrative. You picture that physician dictating after they see the patient, and we've tried to use tools like natural language processing to try to use algorithms to identify meaningful lists from what was said in a high throughput method. But there is still much to be learned about why things were done, which are often not charted. And what we often need to do is, in order to find out the why behind the what and the when, is to go directly to the treating physician. And so that helps establish patterns of care, choice architecture, things that are important in the broader picture of understanding why care is what care is. And, and in the case of this study, we did that. We went to physicians, and we wanted to understand the extent to which they know the data on circulating tumor cell DNA, whether they find that the evidence is compelling or not, and the extent to which they then utilize it in patients with colorectal cancer.