Circulating Cell-Free DNA in Lung Cancer: Are We There Yet?

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Topics include: Treatment and Understanding

Dr. Paul Paik and Dr. Malcolm DeCamp discuss the trajectory of cell-free DNA testing and acknowledge it as an innovative technique because it’s non-invasive and yields bio-marker data. Stay tuned to learn more about this breakthrough research.

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Susan Leclair:

There was an article in some paper not too long ago about testing for circulating DNA for cancer. What about DNA floating around in your bloodstream?

Dr. Paik:                

Right. Free DNA, or the circulating tumor DNA, is something we’ve known about for a fair amount of time in terms of the research arena.  And the general idea is that it’s a blood test.  You’re able to draw a couple of tubes of blood and put it through this technology basically to identify, tumor DNA that gets shed by your cancer cells and that’s floating around and that you’re able to analyze it.  So those tests that we do at the beginning in terms of for lung adenocarcinoma, for instance, figuring out what kind of mutation you have, we’re able to do this also on this circulating DNA.

And the benefits are—are easy to understand.  You don’t need an invasive biopsy, needle biopsy, or surgical biopsy to get the testing done.  You just need to have some blood drawn. So from a diagnostic standpoint its role and its benefit [are] clear. For patients who cannot undergo a biopsy for whatever reason, either medical conditions or location of the tumor, this is an easy way to go ahead and do that.  Its role in terms of other avenues for treatment and for diagnosis are a little bit less clear. 

Some of the research that’s going on right now is in using the circulating DNA as a way to figure out whether or not certain treatments are working, whether or not your cancer is becoming resistant to them, because, again, the idea is that the tumor cells are continuously shedding this DNA into the blood. 

And there have been studies that have shown that we can predict for resistance earlier on. So this will be one of the areas under investigation that’s not quite ready for prime time yet.  And I think, for me, the most important role that circulating DNA is going to have outside of the initial diagnostic process is actually in terms of making that diagnosis of lung cancer itself.  So CT screening is now standard in terms of, um, uh, taking a look at a very high-risk population of patients, uh, for lung cancer.  But the bottom line is that it’s still not perfect. Um, and so anything we can do to try to increase the predictive power for CT screening is going to help.

And so one can envision a role where you do CT screening but also do this blood test for any number of alterations that we know are specific for lung cancer, and maybe this is going to help to boost that predictive power, uh, particularly in our patients who are not at the very high risk for whom screening is not yet a standard.

And I think that is another important way forward because, at the end of the day, the—the patients we’re able to cure are the patients who basically we have to send to Dr. DeCamp.  At the end of the day, that’s the reality and…

Dr. DeCamp:       

…that shouldn’t be a letdown. 

Dr. Paik:                

Right.  This is a—this is a good thing, it’s a great thing. But—but, you know, anything we can do to try to help that, right, is—is where we’re going to see some very meaningful gains. 

Susan Leclair:     

To—to further that along just a little, there’s one thing to know, yes/no. And then the next thing that typically happens with a test is you get a number.  You know, you’re 165. I’m 509.  Someone else is 908. Would quantifying that free DNA, that cancer DNA be valuable say in determining the type of surgery that you might use, that—that someone who has a—a smaller number marker might have a smaller tumor and would be more eligible or might profit better from—from surgical technique A as opposed to somebody who has got a—a number of 5,000.

And—and, therefore, you might look at a surgical technique better.  Is that—is that even possible to do with this? Or—or is this just a pipe dream?  Go ahead, you can say pipe dream

Dr. DeCamp:       

I don’t know if it’s a pipe dream. But I think a lot of valuable tests start out as qualitative tests and tell us about relative risk is the detecting the small amount. Is that meaningful versus a larger amount? And then as you refine the test, it might have more prognostic significance. We do this all the time with PET scanning, which is a test that we use to evaluate the metabolic activity in a tumor or the presence of other metabolic sites in the body. And it has a crude number associated with it called SUV.

And yes, we think tumors with high SUV are more biologically aggressive. But you can still have an early stage high SUV tumor.  And you can have an advanced high SUV tumor, or you can have an advanced tumor that spread to other parts of the body that has not so much SUV. So these—these tools that evolve over time, and I’m not—I can’t speak to the quantitative aspects of this free DNA because it—there are a lot of things that go on in the background to understanding how to normalize that for body size and—and circulating blood volume and all sorts of things to make it a valuable number. So I’ll defer to my colleague who is much brighter than I am.

Dr. Paik:                

So I think Dr. DeCamp is exactly right. So we don’t know what to make of quantity.

And one easy sort of logical comparison is well, let’s say you had a tumor that was 7 centimeters in size versus a tumor that was 1 centimeter in size.  Is there just going to be more of that because there’s more of the cancer? Or, you know, let’s say that the cancer has spread to a lymph node in the middle of the chest, right? So we already know from a plain staging perspective that this is not as good prognostically than if you just had a single tumor in—in a lobe of the lung.  So is there just going to be more tumor DNA, because it’s already spread—learned how to spread to the lymph nodes?

So is that going to add any additional information than just what the plain staging provides us? And the answer is we don’t have an answer. I think these things are going to continue to go on to see whether or not they are able to help define what kind of treatment patients end up getting. And I think an example of that is in postoperative therapy, right?

So in patients who have most kinds of early stage lung cancer now they end up—we end up recommending adjuvant chemotherapy, postoperative chemotherapy.  And we know that there is a survival benefit.  It helps with the cure rate. But we also know that it’s not a very fine tool. We treat everyone, because we have no way of telling who is going to recur and who is not going to recur.  You can imagine that, after the surgery is performed by doing serial blood testing for this circulating DNA, well, maybe what you end up seeing is kind of what they use for breast cancer and plain blood markers like that.

Being able to determine who is going to recur sooner because rather than just taking a look to see whether or not a tumor develops, you begin to see some tumor DNA in the blood.  Or maybe it could be that after the surgery is done, if there is a lot of tumor DNA that’s circulating around, or if it takes a while for it to—to go away, maybe that’s a high-risk population.

So maybe we should focus treatments in the postoperative setting more aggressively on these patients. At the end of the day, being able to use the blood as a kind of biomarker is very powerful and will have a lot of different roles that we’re going to have to be able to define a little bit better as we go forward.  But these things are really the next steps.

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you. 

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Page last updated on September 11, 2015