Circulating Tumor DNA Test May Help Guide GI Cancer Management

Damian McNamara, MA

October 23, 2022

CHARLOTTE, N.C. — Circulating tumor DNA (ctDNA) from patients with gastrointestinal (GI) cancers can reflect treatment response, spare some additional treatment, or signal potential remission in those with metastatic cancer, a new study reveals.

The blood-based test for ctDNA "can detect tumor DNA in circulation and thus identify even a microscopic cancer that would not be found by other conventional modalities like endoscopy or radiographic imaging," Apaar Dadlani, MBBS, who was an internal medicine resident at the University of Louisville in Kentucky at the time of the study, told Medscape Medical News. Dadlani is currently a fellow in transplant hepatology at Baylor College of Medicine in Houston, Texas.

On the other hand, he said, undetectable ctDNA levels raise the likelihood a person does not have malignant cancer cells. In this case, a physician might decide to delay or forgo additional treatment.

The study results suggest that the Signatera ctDNA test (Natera) is sensitive enough to assess tumor burden and can help guide treatment plans for people with locally advanced or metastatic colorectal cancer, he said.

Dadlani will present the findings at the American College of Gastroenterology (ACG) 2022 annual meeting being held in Charlotte, North Carolina, and virtually.

Study Details

Dadlani and colleagues identified 62 patients with GI cancers for whom ctDNA was ordered. Of those, ctDNA results were available for 56 patients; six patients were not included due to insufficient tumor tissue.

The median age at time of diagnosis was 60 years; 53% were women; and 82% were Caucasian, 16% were Black, and 2% were Asian.

Of the patients who could be evaluated, most cancers (82%) detected by ctDNA were colorectal adenocarcinoma. The remainder had other GI malignancies. More than one third (37%) had metastatic cancer.

The biomarker findings corresponded to CT imaging findings in many cases. For example, ctDNA reflected tumor burden in 30 patients (54%).

What happened when ctDNA was undetectable is also noteworthy. In 23% of patients, undetectable levels influenced decisions on systemic therapy and acted as a surrogate measure for gauging treatment response.

"ctDNA was helpful in patients with metastatic colon cancer who had no detectable disease on CT scans after several rounds of treatment," Dadlani said. These were people "who wanted to stop treatment but were anxious that conventional scans may not be picking up residual microscopic disease."

Maintenance therapy was discontinued in five patients with metastatic colorectal cancer because of negative ctDNA and imaging results.

"While the decision to taper or stop treatment is typically made on the basis of negative imaging, a negative ctDNA value reinforced our decision by providing an additional layer of reassurance," Dadlani said. "The fact that all of these patients have not recurred for over a year is in keeping with emerging data on the strong predictive or prognostic ability of this test."

The study included six patients with stage III colorectal cancer with negative ctDNA and imaging results who had significant postoperative complications or were otherwise considered high risk for severe treatment toxicity. In these cases, "ctDNA testing was helpful in selecting out certain frail or ill patients from having to take adjuvant chemotherapy after surgery," Dadlani said.

In another patient with colorectal cancer, ctDNA was undetectable after neoadjuvant therapy, a finding that aligned with pathological complete response on the surgical pathology report.

The ctDNA test was not foolproof, however. Five patients had false-negative ctDNA findings, and one patient had falsely elevated levels.

"In our small study, the false-negative rate was about 9%," Dadlani said. This means if 100 people were tested, nine would have cancer that the test fails to detect.

In six other patients, the researchers could not draw significant conclusions.

"While the ctDNA test appears to be strongly predictive of cancer status, it is not perfect," Dadlani said. "Larger studies will be needed to see how sensitive it really is in predicting presence or absence of cancer."

'An Important Study'

"A blood-based test on circulating tumor DNA is promising as a biomarker for cancer risk, prognosis, or recurrence," Aasma Shaukat, MD, MPH, told Medscape Medical News when asked to comment.

"The study is important, as it aims to correlate the level of circulating tumor DNA in patients with known GI malignancies with tumor burden and decision about using chemotherapy," added Shaukat, director of outcomes research in the Division of Gastroenterology and Hepatology at NYU Langone Health in New York City.

The study is limited by its small sample size "and should be considered hypothesis generating," she said. "But it's a step in the right direction, one of precision oncology and medicine where we can use noninvasive biomarkers to tailor treatment decisions."

For this type of biomarker testing to become mainstream, the biomarker assay needs to be developed and validated in larger diverse cohorts, Shaukat said.

"We also need longitudinal data on association with prognosis, recurrence, and disease-free and overall survival," she said.

The assay is already approved in colon cancer and muscle-invasive bladder cancer, and also to assess response to immunotherapy across all tumor types, Dadlani said.

"The results of ongoing randomized trials will help to better define its role in making treatment decisions in patients with GI cancers," he added.

Dadlani and Shaukat have disclosed no relevant financial relationships.

American College of Gastroenterology (ACG) 2022 Annual Scientific Meeting: ACG Newsworthy Abstract 55. Presented October 26, 2022.

Damian McNamara is a staff journalist based in Miami. He covers a wide range of medical specialties, including infectious diseases, gastroenterology, and critical care. Follow Damian on Twitter: @MedReporter.

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