CHARLOTTE, NC – Circulating tumor DNA (ctDNA) from patients with gastrointestinal (GI) cancers may reflect response to treatment, spare further treatment, or signal potential remission in people with metastatic cancer , reveals a new study.
The blood test for ctDNA “can detect circulating tumor DNA and thereby identify even microscopic cancer that would not be found by other conventional modalities like endoscopy or X-ray imaging,” Apaar Dadlani, MBBS, who was an internal medicine resident in the Division of Transplant Hepatology at the University of Louisville in Kentucky at the time of the study, said Medscape Medical News. Dadlani is currently a Transplant Hepatology Fellow at Baylor College of Medicine in Houston, Texas.
On the other hand, he said, undetectable ctDNA levels increase the likelihood that a person does not have malignant cancer cells. In this case, a doctor might decide to delay or forgo further treatment.
The study results suggest that the Signatera ctDNA (Natera) test is sensitive enough to assess tumor burden and can help guide treatment plans for people with locally advanced or metastatic colorectal cancer, he said. declared.
Dadlani will present the findings at the 2022 American College of Gastroenterology (ACG) Annual Meeting to be held in Charlotte, North Carolina, and virtually.
Dadlani and colleagues identified 62 patients with gastrointestinal cancers for which ctDNA was ordered. Of these, ctDNA results were available for 56 patients; six patients were not included due to insufficient tumor tissue.
The median age at diagnosis was 60; 53% were women; and 82% were Caucasian, 16% were Black, and 2% were Asian.
Of the patients who could be assessed, most cancers (82%) detected by ctDNA were colorectal adenocarcinomas. The rest had other gastrointestinal malignancies. More than a third (37%) had metastatic cancer.
Biomarker results matched CT imaging results in many cases. For example, ctDNA reflected tumor burden in 30 patients (54%).
What happened when the ctDNA was undetectable is also remarkable. In 23% of patients, undetectable levels influenced systemic treatment decisions and acted as a surrogate measure to assess treatment response.
“ctDNA has been useful in patients with metastatic colon cancer who had no detectable disease on CT scans after multiple cycles of treatment,” Dadlani said. These were people “who wanted to stop treatment but were concerned that conventional scans might detect residual microscopic disease”.
Maintenance therapy was discontinued in five patients with metastatic colorectal cancer due to negative ctDNA and imaging results.
“While the decision to reduce or stop treatment is usually made based on negative imaging, a negative ctDNA value reinforced our decision by providing an extra layer of reassurance,” Dadlani said. “The fact that all of these patients have not relapsed for more than a year is consistent 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 at high risk for severe treatment toxicity. In these cases, “cDNA testing has been helpful in preventing some frail or sick patients from undergoing adjuvant chemotherapy after surgery,” Dadlani said.
In another patient with colorectal cancer, ctDNA was undetectable after neoadjuvant therapy, a finding that matched the pathological complete response on the surgical pathology report.
The ctDNA test was not infallible, however. Five patients had false negative cDNA results and one patient had falsely elevated levels.
“In our small study, the false negative rate was about 9%,” Dadlani said. This means that if 100 people were tested, nine would have cancer that the test fails to detect.
In six other patients, the researchers could not draw any significant conclusions.
“Although 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 the presence or absence of cancer.”
“An important study”
“A blood test of circulating tumor DNA shows promise as a biomarker of cancer risk, prognosis, or recurrence,” said Aasma Shaukat, MD, MPH. Medscape Medical News when asked to comment.
“The study is important because it aims to correlate the level of circulating tumor DNA in patients with known gastrointestinal malignancies with tumor burden and the decision to use chemotherapy,” added Shaukat, director of outcome research at 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, that of oncology and precision medicine where we can use non-invasive biomarkers to tailor treatment decisions.”
For this type of biomarker test to become mainstream, the biomarker test needs to be developed and validated in larger, diverse cohorts, Shaukat said.
“We also need longitudinal data on the association with prognosis, recurrence, and disease-free and overall survival,” she said.
The test is already approved in colon cancer and muscle-invasive bladder cancer, as well as to assess response to immunotherapy in all tumor types, Dadlani said.
“Results from ongoing randomized trials will help to better define its role in treatment decision-making in patients with gastrointestinal cancers,” he added.
Dadlani and Shaukat did not disclose any relevant financial relationship.
American College of Gastroenterology (ACG) 2022 Annual Scientific Meeting: ACG Newsworthy Abstract 55. Presented October 26, 2022.
Damian McNamara is a Miami-based staff reporter. It covers a wide range of medical specialties, including infectious diseases, gastroenterology and intensive care. Follow Damien on Twitter: @MedReporter.
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