Incorporating ctDNA Into Routine Practice: Clinical Pearls

Blase Polite, MD: I’ve incorporated ctDNA [circulating tumor DNA] into my practice for the last 2 years. Some of it is a part of clinical trial work, other [parts of it are] standard of care. I’ve found it to be 1 of the most powerful pieces of information that I have for patients. There’s no question that, for your stage II patients and perhaps even some of your low-risk stage III patients, ctDNA can be very helpful. For patients with IIA and IIB colon cancer, I tend not to treat most of these patients with chemotherapy based on the available data, but finding the patient circulating tumor DNA negative gives the patient and me reassurance that we’re probably safe not treating. On the other hand, if they’re ctDNA positive, I treat these patients understanding that the question is subject to the trials that we’ve discussed. I’d enroll these patients in clinical trials and CIRCULATE-US when they become available. Absent that, I’d give the stage II ctDNA positive population chemotherapy. For some of your IIIA patients, you could consider the same. That’s a very low-risk population that probably doesn’t need even 3 months of chemotherapy. If they’re ctDNA negative, is that a population that can watch? From an informed decision-making standpoint, I found that to be helpful for patients to see, and it gives reassurances.

The other place that I found a lot of interest in ctDNA is in the stage IV NED [no evidence of disease] population. For patients with liver and lung metastases who we’ve resected, we’re making the decision whether to get chemotherapy. The randomized clinical trials tell us that we don’t benefit these patients with chemotherapy in practice, but I find that most oncologists have a hard time not giving a patient with metastatic disease resected chemotherapy; it doesn’t feel right. The surgeons don’t like us not giving chemotherapy to this population, but if I find them ctDNA negative, then the patient and the surgeons seem to calm down a bit.

Alternatively, if they’re positive, that’s a population that we should probably treat. I could be wrong, it may be the reverse of that. Maybe we should be aggressively treating ctDNA negative and not treating ctDNA positive. But until other information comes out, it gives me assurance to not give chemotherapy when the data support not doing so. I try to isolate high-risk patients who would benefit most from chemotherapy.

In our tumor boards, we’re constantly bringing up ctDNA results and recommending ctDNA testing to patients. When you consider the overall strategy and technology, this should be a tumor-agnostic strategy. There’s no reason that this technology shouldn’t work in pancreatic cancer, lung cancer, breast cancer, etc. In the GI [gastrointestinal] world, I’m excited to start looking at it in our patients with pancreatic cancer. In the colon world, we’ve got a lot of good data the most powerful prognostic indicator postoperatively, in terms of ctDNA positivity or negativity, is much better than CEA [carcinoembryonic antigen]. This is something I encourage people to start incorporating into their practice. As CIRCULATE-US becomes available, if you have the apparatus to run clinical trials, this is 1 of our most critical trials. It seeks an answer: can we de-escalate therapy in the negatives and escalate therapy in the positives and improve outcomes for these patients?

Transcript edited for clarity.