Using ctDNA MRD Monitoring During Active Metastatic CRC Treatment

Holly Chitwood, DNP, APRN, FNP-C, AGACNP-BC

Monitoring circulating tumor DNA (ctDNA) may provide providers a glimpse into how a patient is responding to treatment before imaging modalities can show outcomes like progression, according to Holly Chitwood, DNP, APRN, FNP-C, AGACNP-BC.

“This is a new technology that we have,” she told Oncology Nursing News. “It is basically looking at what is in your blood to see how much circulating tumor DNA is floating around.”

Chitwood is an assistant professor in the College of Nursing at the University of Kentucky in Lexington, as well as a practicing oncology advanced registered nurse practitioner who primarily cares for patients with gastrointestinal, hepatic-biliary and sarcoma tumors in her clinic.

She recently published an article in the Clinical Journal of Oncology Nursing about the potential applications of ctDNA in monitoring minimal residual disease (MRD) in patients with colorectal cancer.¹ In an interview with Oncology Nursing News, she walked through one of the case studies from the article, highlighting how the team leveraged this tool throughout the patient’s treatment journey.

A Metastatic Colorectal Cancer Diagnosis

Chitwood presented an example of a 70-year-old male patient who arrived in her clinic a few years ago with persistent iron deficiency, anemia, and abdominal discomfort. He also had been experiencing tenesmus, or the frequent urge to defecate. These are signs pointing to colorectal cancer, explained Chitwood.

His providers ordered a colonoscopy, at which point an ulcerated and necrotic colon mass was identified. The patient had a grade 2 adenocarcinoma with a mass of 7.5 cm by 6 cm, and 3 of the 23 nodes were positive. Staging revealed that his disease was metastatic; the final staging was pT3pN1pM1.

“This patient had a mass in the colon, but he also had pulmonary metastasis and adrenal metastasis, which is common with colorectal cancer. [He] did not have liver metastasis, which was a good thing,” she described.

The Decision to Prescribe FOLFIRI

FOLFOX is the standard-of-care therapy in this setting, according to Chitwood. However, upon assessment, the team discovered that this patient was dealing with baseline peripheral neuropathy, as well as hypertension. Although the hypertension was being managed by the primary care doctor, the team decided to proceed with a more tolerable regimen.

“I would have given this patient an overall ECOG performance status of 1, maybe 2, but a solid 1 on most days,” Chitwood said. She explained that they chose FOLFIRI, a combination of 5-fluorouracil, leucovorin, and irinotecan, instead because this approach does not use oxaliplatin and is, therefore, more tolerable than FOLFOX.

Watching the MRD Levels Change

As the patient began treatment, the team noted that his MRD levels declined. As a treatment resistance developed over time, however, that level slowly began to rise. Whenever the patient was switched to a new therapy, the level would come back down.

“It kind of fluctuated with what was happening with the patient clinically and was a little bit ahead of what we were seeing on imaging,” Chitwood recalled.

At baseline, the patient’s ctDNA measurement had been between 600 and 700 MTM/mL. Once treatment started, this number dropped to almost 0.

“[We saw] a dramatic drop within the first few months of treatment,” Chitwood said. “It dropped down to 0.16 MTM/mL in the first few months of treatment.”

After a while, the number began to incrementally rise, but the disease was still stable, according to the scans. Then, at about the 5-month mark, the ctDNA registered at 75 MTM/mL. However, the imaging still showed stable outcomes.

“That was a pretty big jump,” she said. “Of course, we did imaging—but the imaging was stable, the patient was doing OK on treatment. So, we didn't make any treatment changes.”

Three months later, the CT imaging demonstrated pulmonary progression. Treatment recommenced on a biweekly basis. The team added panitumumab (Vectibix) to the patient’s regimen. When the patient developed a grade 3 rash with panitumumab, cetuximab (Erbitux) was substituted, but the patient eventually had to discontinue cetuximab as well. His ctDNA was 131 MTM/mL, but over the next 3 and 6 months, respectively, his ctDNA dropped down to 0.76 MTM/mL and 1.9 MTM/mL.

Over a year later, CT imaging showed evidence of pulmonary progression. The patient’s ctDNA was 300 MTM/mL, so he made the decision to restart his chemotherapy.

Considerations as a Provider

In her practice, Chitwood has consistently observed that ctDNA can detect MRD before imaging.

“In this case, and in a lot of my patients, you will see ctDNA is about anywhere from 2 to 3 months ahead, predating what you will see on imaging,” she shared.

She explained that as a provider, it can be challenging to determine whether to trust the MRD number that the ctDNA is showing. Without additional evidence of progression, it may be an insufficient reason to change treatment regimens.

“When you are starting to measure minimal residual disease, you have got to decide [first], how much do you trust that number, [and second], do you have actually enough evidence to make drastic changes in treatment that may come with more toxicities for your patient,” she said.

Currently, there are no clinical guidelines on how to interpret this into practice and exactly interpret the numbers—although ctDNA is gaining momentum in clinical research and more data are on the way, she said. However, if the MRD number is rising, that may suggest that the patient should have some scans sooner rather than later.

“Generally, with colorectal cancer—and I speak to colorectal cancer because that's my specialty—patients are getting scans every 3 to 4 months,” she explained. “If the results come back positive, then you would need to consider maybe doing a short interim scan.”

“So, when you see a number consecutively rising and you don't have it on imaging, you can expect that it's going to happen,” she underscored. “That is what we see in practice. That is the take-home here.”

Talking to Patients About the Numbers

When patients understand that their result is positive, they may become worried or want to change their treatments. As a provider, it is important to remember this and be very clear in how the team will proceed following these results.

“You have to be very judicious in explaining the results, especially if you have a positive result, and the patient should be included in the decision-making,” Chitwood said. “A lot of times it gets a little sticky; patients will come in and be like, ‘What are my numbers?’ or ‘I saw my numbers in my chart. Are you worried?’ ”

Although ctDNA monitoring is a very promising prognostic method, it should not be used alone to determine treatment decisions, she concluded.

“You should have it as a piece of the picture, with the imaging, and how the patient's doing overall, before you change treatment options.”

Reference

Chitwood H, Myers A. Use of circulating tumor DNA to monitor minimal residual disease among patients with colorectal cancer. Clin J Oncol Nurs. 2023;27(4):369-374. doi:10.1188/23.CJON.369-374