Dr Lieu Talks ctDNA to Guide CRC Treatment

Christopher Lieu, MD, University of Colorado, shares insights to how ctDNA can detect MRD and determine genomic characterization of tumors in CRC at the 2022 GDU GI Meeting. 

Transcript

I'm Chris Lieu, from the University of Colorado Cancer Center. I'm a GI medical oncologist and service the associate director for clinical research.

So today we discuss this concept of circulating tumor DNA. I'm going to explain what circulating tumor DNA is and how we use this test to potentially look for cancer and manage treatment for cancer, particularly colorectal cancer.

So when we talk about circulating tumor DNA, we're talking about a fraction of what we call cell-free DNA. So within our bodies, we have a lot of cell-free DNA that gets released into our bloodstream. And this usually happens when cells either undergo apoptosis or turnover. But we know that in our patients with active cancer, there can be the presence of something called circulating tumor DNA, which are fragments of tumor DNA that are released into the bloodstream. Now ctDNA or circulating tumor DNA is harmless to the body and it gets metabolized, usually within days, sometimes weeks.

But regardless of all the cell-free DNA that's in our patients' bodies, if we detect circulating tumor DNA, we can do two major things with that information. Number one, we can utilize that information to find out whether there's the presence of cancer inside the body. We call this minimal residual disease. If a patient has the presence of ctDNA after curative surgical resection, maybe after adjuvant chemotherapy, we really start to worry that there is still the presence of disease in the body that we just can't detect, either with our standard blood tests or with our radiological imaging tests, like CT, PET scans or MRI.

The question is whether or not we can utilize this information to better enhance our treatment for patients and this is where clinical trials really come into play. Can we utilize this information to maybe prevent giving chemotherapy to patients who are already cured with surgery or can we utilize this information to know if we need to do something in addition to our standard surgery and adjuvant therapy? And those trials are ongoing.

One of the debates that we're having in regards to the utilization of ctDNA in the minimal residual disease setting is whether it's ready for PRIMETIME. Can we utilize this information to guide adjuvant therapy for patients who have undergone curative resection? And in this case, we're talking about colorectal cancer. Now we know that the trials are ongoing, but what we've done in our session is present some data in regards to what happens to ctDNA and patients that receive adjuvant chemotherapy, what happens to patients with ctDNA that do not get adjuvant chemotherapy and what does their disease-free survival look like.

The other thing that we utilize this information for is to determine genomic characterization of tumors in a real-time setting in patients with metastatic colorectal cancer. So what if you have a patient with metastatic colorectal cancer that you know is stage 4, but you cannot obtain tissue biopsy, because it's inaccessible? Can we utilize something like ctDNA, a liquid biopsy, to look for some of the genomic markers that we use to guide our therapy in colorectal cancer, such as KRAS, NRAS and BRAF?