Circulating Tumor DNA and MRD Assessment in Colorectal Cancer

Opinion
Video

The expert panel offers closing thoughts on MRD assessment and how ctDNA has been incorporated into clinical practice in the treatment of colorectal cancer.

Transcript:

Tanios S. Bekaii-Saab, MD: Moving beyond colorectal cancer, can you talk at a high level about other areas where the field of MRD [minimal residual disease] assessment is being investigated?

Joleen Hubbard, MD: We saw multiple abstracts in different malignancies at ASCO [American Society of Clinical Oncology Annual Meeting]. A lot of them were more about feasibility, showing that we have elevated ctDNA [circulating tumor DNA], we treat patients, and a decline in the ctDNA corresponds with better progression-free survival. That’s becoming more utilized in other tumors. One interesting abstract [looked at] patients who had brain metastases from solid tumors and whether they had disease outside the brain vs just brain metastases. It was interesting that the ctDNA could pick up the different mutations and actionable mutations so that we can put patients on a trial or have a directed therapy against those brain metastases. Sometimes there’s a difference between the primary tumor and the metastatic disease in the brain, and to be able to pick up that difference and potentially have an actionable mutation—a drug that could target that mutation—was really fascinating. We need more data, but obviously we’re not going to do big brain biopsies and get tissue for NGS [next-generation sequencing]. It’s nice that using circulating tumor DNA, we could find mutations that might be actionable.

Tanios S. Bekaii-Saab, MD: Interesting. I assume that when you breach that blood-brain barrier, you’re going to have a 2-way street. You can depict the ctDNA, which is fantastic. That hasn’t been limiting factor previously. Dan, how have you incorporated ctDNA analysis into your practice?

Daniel H. Ahn, DO: Most of the interest has been in the early stage setting to detect early recurrence in those who undergo surgical resection, but in my practice, in addition to using it for that, I’ve expanded to other special areas of interest. For those of us who treat a lot of colorectal cancer, this is a disease that can often present with oligometastatic disease. At the time of presentation or with metachronous disease later, these patients undergo surgical resection. That’s where there’s a lot of utility or interest, monitoring not only patients who go for curative-intense treatment for early stage disease but also those with more advanced disease. If I have a patient who presents with metastatic disease, I’m able to get them to a curative intense surgery. After they complete pseudo adjuvant chemotherapy, that’s where there’s a lot of interest, at least in my perspective, to use the test as an adjunct to early stage disease.

Tanios S. Bekaii-Saab, MD: Aparna, I’m going to let you close this. Do any other questions remain about the potential utility of circulating tumor DNA? Let’s say cancer or even precancerous conditions.

Aparna Parikh, MD, MS: You’re opening a black box there a little. The precancer early detection space isn’t going away. It’s burgeoning with data, and the landscape is rapidly evolving. In the same way there are different types of tests emerging in the MRD space, there are multiple tests emerging in the early cancer detection space. Multicancer early detection tests are looking for—with 1 blood test—different blood-based analytes based on the type of tests. Some are methylation only, some fragmentation, some proteomics, plus genomics, plus fragmentation. There are different scenarios for multicancer early detections being developed. But there are also tumor-specific early detection tests being developed. There’s a test for colon cancer by Cologuard. They have shown that data. They haven’t published them yet, but they’ve been presented. It’s interesting. Unfortunately, the advanced adenoma detection rate isn’t great for that, but the cancer-detection rate is. There’s a lot of discussion around if we’re not doing great meeting the needs of screening all our patients with colonoscopies or a stool-based test, can an integrated point-of-care, blood-based test help with our adherence to screening. Blood-based biomarkers aren’t going away. It will probably be some combination in all these settings of different blood-based multianalytes, spanning the spectrum from early detection to late-stage monitoring and genomic sequencing.

Tanios S. Bekaii-Saab, MD: Excellent. Thank you. I thank Drs Ahn, Hubbard, and Parikh for joining us in this lively discussion on the use of circulating tumor DNA brought to you by Cancer Network®. Thank you to our viewing audience. We hope you found this interactive discussion to be informative and beneficial to your patients and clinical practice. Thank you all.

Transcript edited for clarity.

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