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Potential Use of ctDNA and MRD in CRC

Insights From: Axel Grothey, MD, West Cancer Center, University of Tennessee; John Marshall, MD, Ruesch Center for the Cure of Gastrointestinal Cancers
Published: Wednesday, Feb 26, 2020



Transcript: 

John Marshall, MD: We now have established very clear guidelines that say we have to know certain molecular characteristics of a patient’s tumor before we treat them. That’s standard. It’s in the standard guidelines. Whether you do 1, 2, 3, 4 tests in your own laboratory by your own pathologist or you send out a much broader test is a personal decision.

What has happened over the last decade though is that we now have both FDA approval as well as insurance approval, if you will, to do broader testing. The benefit of doing the broader testing is you’re finding rarer mutations, like the MSI [microsatellite instability], like NTRK, like some of these others that you wouldn’t normally look for in a routine colon cancer. But if you do the broader testing, you find the needles in the haystack that can really transform a patient’s care.

This new technology, this ctDNA [circulating tumor DNA] technology, has come forward. You can actually order the test. There’s an explosion of data to support using this kind of technology. So we have to get up to speed very quickly on what this test can and cannot do. After a patient has had a surgery for their cancer, for their colon cancer, what I want is a test that simply tells me the patient is cured from surgery, and therefore, does not need chemotherapy; or the patient is not cured, there’s still cancer around, and chemotherapy will fix that; or better still, they are not cured and the chemotherapy that I normally would give won’t do it. That patient needs a clinical trial.

I think of it as sort of a Harry Potter magic sorting hat, where we can distinguish a patient into those 3 categories. What are we doing now? Well, we’re treating all of those patients with chemotherapy, only knowing that we’re helping this small subgroup.

This is an incredibly valuable test. If I could go after a patient has had surgery and say, “There’s no evidence of cancer in you now,” maybe I don’t give chemotherapy, or maybe I give less chemotherapy. I don’t put patients through 3 to 6 months of the burden of chemotherapy. On the other hand, if there still is circulating tumor DNA after surgery, then I know almost 100% that patient’s cancer is coming back. Then I have no hesitation about giving that patient chemotherapy. And further still, I can monitor whether the DNA then goes away, right? Did the chemotherapy do its job and the cancer has gone away? And so, then we know, as best we can today, that that patient has benefited from that chemotherapy, maybe even being cured.

The problem is the other side of this formula. If the patient’s blood test is negative, that’s a very good sign, don’t get me wrong. It really does suggest that they probably don’t have cancer. Still, the reality is there’s a small percentage who have a negative blood test whose cancer still comes back. The test was wrong. It missed it, okay?

Where we’re nervous as oncologists is we don’t want to miss anybody who we might be able to cure with the chemotherapy. And so, where the test falls short today is when it’s negative. “Am I sure I don’t need to give you chemotherapy? Could I give you less chemotherapy?” I’m not 100% sure.

Where it’s very useful is when it’s positive. “I know you’re in trouble. I know we should give chemotherapy, and I can track your outcome.” So, you can order it today. You can get the result back. But it’s critical that we understand the subtleties of this test so we can make the best decision with our patients.

Transcript Edited for Clarity
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Transcript: 

John Marshall, MD: We now have established very clear guidelines that say we have to know certain molecular characteristics of a patient’s tumor before we treat them. That’s standard. It’s in the standard guidelines. Whether you do 1, 2, 3, 4 tests in your own laboratory by your own pathologist or you send out a much broader test is a personal decision.

What has happened over the last decade though is that we now have both FDA approval as well as insurance approval, if you will, to do broader testing. The benefit of doing the broader testing is you’re finding rarer mutations, like the MSI [microsatellite instability], like NTRK, like some of these others that you wouldn’t normally look for in a routine colon cancer. But if you do the broader testing, you find the needles in the haystack that can really transform a patient’s care.

This new technology, this ctDNA [circulating tumor DNA] technology, has come forward. You can actually order the test. There’s an explosion of data to support using this kind of technology. So we have to get up to speed very quickly on what this test can and cannot do. After a patient has had a surgery for their cancer, for their colon cancer, what I want is a test that simply tells me the patient is cured from surgery, and therefore, does not need chemotherapy; or the patient is not cured, there’s still cancer around, and chemotherapy will fix that; or better still, they are not cured and the chemotherapy that I normally would give won’t do it. That patient needs a clinical trial.

I think of it as sort of a Harry Potter magic sorting hat, where we can distinguish a patient into those 3 categories. What are we doing now? Well, we’re treating all of those patients with chemotherapy, only knowing that we’re helping this small subgroup.

This is an incredibly valuable test. If I could go after a patient has had surgery and say, “There’s no evidence of cancer in you now,” maybe I don’t give chemotherapy, or maybe I give less chemotherapy. I don’t put patients through 3 to 6 months of the burden of chemotherapy. On the other hand, if there still is circulating tumor DNA after surgery, then I know almost 100% that patient’s cancer is coming back. Then I have no hesitation about giving that patient chemotherapy. And further still, I can monitor whether the DNA then goes away, right? Did the chemotherapy do its job and the cancer has gone away? And so, then we know, as best we can today, that that patient has benefited from that chemotherapy, maybe even being cured.

The problem is the other side of this formula. If the patient’s blood test is negative, that’s a very good sign, don’t get me wrong. It really does suggest that they probably don’t have cancer. Still, the reality is there’s a small percentage who have a negative blood test whose cancer still comes back. The test was wrong. It missed it, okay?

Where we’re nervous as oncologists is we don’t want to miss anybody who we might be able to cure with the chemotherapy. And so, where the test falls short today is when it’s negative. “Am I sure I don’t need to give you chemotherapy? Could I give you less chemotherapy?” I’m not 100% sure.

Where it’s very useful is when it’s positive. “I know you’re in trouble. I know we should give chemotherapy, and I can track your outcome.” So, you can order it today. You can get the result back. But it’s critical that we understand the subtleties of this test so we can make the best decision with our patients.

Transcript Edited for Clarity
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