Expert: Circulating tumor DNA is ‘hidden link’ to control 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 when we think back to the early years of cancer, the thought was that the cancer was a disease of an organ. It is a disease of the breast and as a result the radical mastectomy removed the breast, the muscles under the breast, all the lymphatic vessels of the breast area, all the vessels of the breast area. And those were major operations with serious side effects and really disfiguring [to] the patient. When we discovered that cancer cells are microscopic – thousands of fits on the tip of a pin – they enter the bloodstream and bloodstream before the tumors are large enough to be seen, we realized that this is no longer really a disease of an organ , but a disease of a cell. And those cells then circulate, so we had to start implementing, we could use less surgery, but we had to give a total body treatment in the form of adjuvant treatment, adjuvant chemotherapy — or adjuvant hormonal therapy in the case of breast — to try destroy those cells that did leak into the bloodstream. Now we’ve evolved further to understand that it’s all a genetics-based process where an abnormal gene expression leads to the behavior of the cell, causing those cells to leak into the bloodstream before the tumors are big enough to be seen. So this evolution over time has reshaped our ability to understand and think about cancer treatment.

Well, we now understand that if 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 such a hidden link to what’s going on with the cancer. And it’s a hidden link that gives us a sensitivity to understanding far greater than what we can get with imaging. With imaging we are limited to a tumor size of a centimeter, maybe as small as half a centimeter. With circulating tumor DNA, we get 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 is a very interesting tool.

It’s already been useful in liquid tumors because that was the idea that the cells are already alive in the blood, there should still be elements of the DNA. But we realize that it is also present in solid tumors. And I can imagine one day, and it may be 10 years from now, we don’t do CT scans every 3 months, but instead take a blood sample to see if circulating tumor DNA is still in the body. is, instead of trying to look at a CT scan to see if there is still a large cluster of cancer cells.

How is ctDNA specifically useful in colorectal cancer?

Bruce Feinberg, DO: So in terms of the solid tumors in which circulating tumor cell-free DNA has been found and studied, there are a handful of them that are starting to pop up where the studies are mature, sophisticated and large enough to provide evidence on which to grow this theory that we are moving beyond the limits. from traditional imaging to another way of assessing the persistence of tumors in the body. And colorectal cancer is one of those tumors that has been heavily studied, in which there is published data. And because there’s strong evidence now, the question for us as researchers was, now that there’s evidence, to what extent is that evidence recognized? And is it valued to the extent that it is used? And that was the reason for the investigation.

How was your research conducted and what was its purpose?

Bruce Feinberg, DO: Most of our work consists of direct contact with prescribing physicians, treating physicians. Much of the observation data in the past has focused on using claims data, which tells you what was done and when it was done, arguing a fee-for-service system, anything done is charged, and so there would be an invoice record. And that was the foundation when we moved to electronic health records. The idea is that whatever is in the health record could be another source of data. The problem with medical records is that a lot of what’s in it isn’t structured, meaning it’s just an open story. You imagine that doctor dictating after they see the patient, and we tried to use tools like natural language processing to try to use algorithms to identify meaningful lists based on what was said in a high-throughput method. But there is still a lot to learn about why things have been done, which are often uncharted. And what we often have to do is, to find out the why behind the what and the when, go directly to the treating doctor. And that helps to determine care patterns, choice architecture, matters that are important in the broader picture of understanding why care is what care is. And in the case of this study, we did. We went to doctors and we wanted to understand to what extent they know the data on circulating tumor cell DNA, whether they find the evidence compelling or not, and to what extent they then use it in patients with colorectal cancer.

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