Expert: Circulating tumor DNA is a "hidden link" for monitoring colorectal and other cancers

Expert: Circulating tumor DNA is a “hidden link” for monitoring colorectal and other cancers

In an interview with Pharmacy Times Bruce Feinberg, DO, vice president and chief physician 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 the future at the annual meeting of the American Society for Clinical Oncology (ASCO) 2022. in other cancers.

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

Bruce Feinberg, DO: So interestingly, when we think back to the early years of cancer, we thought cancer was an organ disease. It is a disease of the breast, and as a result, radical mastectomy has removed the breasts, the muscles under the breasts, all the lymphatic vessels in the breast area, all the blood vessels in the breast area. And these were radical operations with serious side effects and really disfiguring [to] patient. When we learned that cancer cells were microscopic — thousands of them fit on a pinhead — they enter the circulation and the bloodstream before the tumors are large enough to be seen, we realized that it was no longer the case. organ disease, it is a cell disease. And those cells then circulate, so we had to start introducing, we could use fewer surgeries, but we had to give total body treatment in the form of adjuvant therapy, adjuvant chemotherapy – or adjuvant hormone therapy in case of breast – in order to try to destroy those cells that leaking into circulation. We have now evolved to understand that this is all a genetic process in which abnormal gene expression leads to cell behavior, which then leads to the cells escaping into circulation before the tumors are large enough to be seen. . Thus, over time, these developments have reformulated our ability to understand and think about cancer treatment.

We now understand that as these cells enter the circulation, the cells themselves may not remain intact, but their DNA signatures will remain – the chemical DNA is still there. And so cellular free-circulating tumor DNA is this kind of hidden connection to what happens to cancer. And it’s a hidden link that gives us a sensitivity of understanding that is much greater than what we can gain by displaying. When imaging, we are limited to the size of the tumor, which is a centimeter, maybe up to half a centimeter. With circulating tumor DNA, we get to several exponential levels below that, and it’s a way to truly understand how much cancer there may be in a patient’s body at the submicroscopic level. So it’s a really interesting tool.

It was already useful in liquid tumors, because it was thought that the cells already lived in the blood, there should still be elements of DNA. But we realize that it is also present in solid tumors. And I can imagine the day, and it could be in 10 years, that we don’t do a CT scan every 3 months, but instead take a blood sample to see if circulating tumor DNA is still present in the body. instead of trying 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 as for the solid tumors in which circulating tumor cell-free DNA has been found and studied, there are several that are beginning to emerge where studies have matured, refined, large enough to provide evidence to extend this the theory that we can move beyond traditional imaging to another way of assessing tumor persistence in the body. And colon and rectal cancer is one of those tumors that has been extensively studied for which there is published data. And since there is strong evidence now, the question for us as researchers has been, now that there is evidence, to what extent is this evidence accepted? And is it valued to the extent that it is used? And that was the reason for the research.

How did your research go and what was its goal?

Bruce Feinberg, DO: Most of our work is that we contact the prescribing physicians, the attending physicians. So much observational data has historically focused on the use of claims data that tells you what and when was done, with the argument being a service charge system, everything that is done will be charged, so be a billing record. And that was the basis when we switched to electronic medical records. The idea is that everything in the medical record could then be another source of data. The problem with medical records is that much of what is there is not structured, which means it’s just an open story. Imagine that a doctor dictates after seeing a patient, and we have tried to use tools such as natural language processing to try to use algorithms to identify meaningful lists from what has been said in a high-performance method. But we still have a lot to learn about why things were done that are often not mapped. And what we often have to do is go directly to the attending physician to find out why and what. And so it helps to create patterns of care, the choice of architecture, things that are important in a broader view of understanding why care is what care is. And in the case of this study, we did it. We went to the doctors and wanted to understand the extent to which they knew about the circulating DNA data in tumor cells, whether they found the evidence to be convincing or not, and the extent to which they used it in patients with colorectal cancer.

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