ctDNA Can Detect MRD and Early Cancer Recurrence in Colorectal Cancer

Circulating tumor DNA (ctDNA) can be analyzed in patients with cancer to detect minimal residual disease (MRD). Two abstracts, presented at the American Association for Cancer Research Annual Meeting 2019, held March 29 to April 3 in Atlanta, Georgia, evaluated ctDNA analysis and ways of tracking MRD.

Researchers on one abstract¹ noted that a low concentration of ctDNA, especially in early-stage cancers, makes it more difficult to detect tumor-derived cell-free DNA (cfDNA). They analyzed a custom next-generation sequencing assay, MSK-ACCESS (Analysis of Circulating cfDNA to Examine Somatic Status), to see how well it detected somatic mutations from plasma.

The tool leverages a data set of more than 30,000 tumors profiled by the Memorial Sloan Kettering Cancer Center tumor sequencing assay, MSK-IMPACT. They found that MSK-ACCESS detected low-frequency variants with high confidence.

The researchers collected plasma samples from 40 healthy individuals and 70 patients with cancer who had a range of somatic mutations in 11 genes. They applied MSK-ACCESS to monitor variants from pre- and postsurgical cfDNA samples from 9 patients with colorectal adenocarcinoma. They found that ctDNA was detected in 6 of 9 (66%) of presurgical samples and in 3 of 6 (50%) of postsurgical samples, which indicates that the assay can successfully detect MRD.

In the second abstract,² the authors evaluated using ctDNA to detect MRD in patients with colorectal cancer.

“Although the prognosis of [CRC] has improved in the past decade, a subset of CRC patients may still suffer from relapse due to the progression from [MRD] after surgical resection,” the authors explained.

They collected plasma samples from 45 patients with CRC who underwent surgical resection. Blood samples were also taken just before surgery and postoperative samples were collected multiple times, and cfDNA/RNA were extracted and subjected to next-generation sequencing.

The authors found that 27 of 39 (69%) of preoperative patients had at least 2 copies of somatic mutations. Seven samples had an increase in mutant allele frequency (MAF) after surgery with a median increase ranging from 1.2-fold to 7.9-fold. One of these patients relapsed 6 months after the primary tumor resection. The patient carried BRAF-V600E with an MAF of 0.067% before surgery, but at the time of recurrence there was an 8-fold increase (0.530%), which increased further to 0.685% at the time of surgery.

“Our current results indicate that ctDNA analysis before and after resection allows the detection of MRD in CRC patients,” the authors concluded. “The integration of ctDNA analysis with current standard monitoring guidelines holds great promise in the early detection of recurrence to allow clinical intervention to be applied promptly.”

References

1. Hasan MM, Patel J, Johnson I, et al. Tracking minimal residual disease in post-operative cell-free DNA using MSK-ACCESS. Presented at: American Association for Cancer Research Annual Meeting 2019; March 29-April 3; Atlanta, GA. Abstract 1387/26.

2. Chan HT, Nagayama S, Chin YM, et al. The application of circulating tumor DNA analysis for detecting minimal residual disease and predicting recurrence in colorectal cancer patients. Presented at: American Association for Cancer Research Annual Meeting 2019; March 29-April 3; Atlanta, GA. Abstract 1338/7.