Blood test identifies colon cancer patients who benefit from anti-inflammatory medication

A blood test could help doctors decide which patients with colon cancer should receive anti-inflammatory medication along with chemotherapy after surgery, according to new study in JAMA Oncology. Based on data from an Alliance for Clinical Trials in Oncology study, this finding could lead to more personalized treatments and better outcomes for patients.

Colon cancer is one of the most common cancers in the United States with about 110,000 new cases diagnosed each year, according to the American Cancer Society. Even after surgery and chemotherapy, up to 40% of patients with stage III disease see their colon cancer return. Celecoxib belongs to a class of medicines known as NSAIDs (nonsteroidal anti-inflammatory drugs), which include common drugs like aspirin and ibuprofen. Celecoxib is a prescription NSAID often used to reduce pain from arthritis.

Researchers have suspected that the anti-inflammatory properties in NSAIDs could prevent colon cancer from coming back since inflammation plays a role in cancer growth. However, clinical trials have not shown a clear benefit for all patients, leaving doctors unsure who should take them.

This new analysis offers insight. Researchers looked at circulating tumor DNA (ctDNA), tiny fragments of cancer DNA that can remain in the blood after surgery. Patients who tested positive for ctDNA after surgery were much more likely to have their cancer return. For these high-risk patients, adding celecoxib to chemotherapy significantly improved survival. Patients without ctDNA did not benefit, meaning they could avoid taking extra medication unnecessarily. To measure ctDNA, clinicians take a simple blood test from the patient and use gene sequencing to analyze the sample.

We've known that NSAIDs may help prevent recurrence in some patients with colon cancer, but until now, we didn't know how to identify them. Measuring circulating tumor DNA levels after surgery using this blood test has the potential to change that."

George Q. Zhang, MD, MPH, lead study author, general surgery resident, Brigham and Women's Hospital

"The main goal of CALGB (Alliance) 80702 was to determine if adding celecoxib to chemotherapy after surgery for colon cancer improved survival," said study chair Jeffrey Meyerhardt, MD, MPH, a medical oncologist at the Dana-Farber Cancer Institute. "The initial trial didn't definitively confirm our hypothesis; however, we saw that some patients did benefit from adding celecoxib and we then sought to identify them. This study identified a subset of patients that had detectable ctDNA after surgery as a group that benefited from adding celecoxib to chemo after surgery."

With support from the National Cancer Institute, CALGB (Alliance) 80702 enrolled more than 2,500 patients with stage III colorectal cancer who had initially had surgery to remove their tumor. This study looked at the ctDNA biospecimens of 940 individuals – 767 of whom were ctDNA negative and 173 that were ctDNA positive. In patients who tested ctDNA positive, the addition of celecoxib compared to placebo nearly doubled disease-free survival over three years, 41% compared to 22.6%. Over five years, the overall survival for patients who were ctDNA positive was 61.6% for those who received celecoxib, compared to 39.9% in those in the placebo group. 

"Although these results are very encouraging, additional prospective research will be necessary to further validate them," Dr. Zhang added.