Two Key Uses for ctDNA in the Clinical Setting

Two Key Uses for ctDNA in the Clinical Setting

Mark G. Kris, MD, FASCO: So, there's two big uses for “ct” or circulating tumor DNA today. Probably the biggest use and the one that's most established and part of guidelines is to use it as a diagnostic test to look for the presence of certain somatic mutations and rearrangements that would lead you to a targeted therapy. I mean, that's the main issue. That's not what we're really talking about in this perioperative setting, though, it's critically important to get those molecular characteristics because they inform your choice of neoadjuvant radiation therapy. So, for example, patients that have mutations in EGFR or rearrangements in the ALK gene, they are much less likely to gain substantial benefit from immunotherapeutics. So, finding that abnormality pushes a doc away from recommending a regimen that would have immunotherapeutic either in neoadjuvant, or adjuvant setting. Actually, the recent approval of nivolumab with chemotherapy neoadjuvantly specifically says it shouldn't be used in patients that have EGFR and ALK. So, it's helpful for those patients, and obviously a patient has EGFR, you would think about using EGFR targeted agent like osimertinib in the adjuvant setting so the test is very helpful for that. Unfortunately, you need a certain amount of DNA to be present. And the amount of DNA does associate with the extent of the cancer. So, the tinier the cancer, the less DNA you have in the bloodstream to detect. So, there's still a lot of controversy actually about how a tissue test in a DNA test stack up against each other. The numbers that people throw out, are that the cell free DNA diagnostic test is good about 75% of what the tissue test is. And the number for people with early-stage cancer people that are like surgical candidates is somewhere between 20% and 40%, what you would find enough DNA to test for. So, while it can be very useful when you find the DNA, unfortunately, there are situations where you just don't find it and you have to rely on tissue. So, I think in 2022, you still need tissue, though the DNA can be helpful. So, I'm talking now about using it as a diagnostic test. The other use, following the example of other kinds of cancers, is to look for evidence of cancer in the body, kind of at the molecular level. To look for DNA in the blood, that would signal the presence of cancer, and particularly DNA that was important for that cancer. People have done that with chronic myelogenous leukemia with just tumors and now we're moving into doing that with lung. So, the idea here would be to know the mutational landscape of a person's cancer, to see if those mutations can be found in blood. And if they can be found in blood, use those mutations as a way to see how effective cancer therapy might be, or to herald the return of the cancer, find it in as early as possible a stage, or hopefully you can intervene and do a better job taking care of the patient and hopefully even give them another chance of being cured. So, two things with DNA diagnostic, or looking for the term is minimal residual disease.

Transcript Edited for Clarity