Liquid Biopsy After Hepatectomy Promising Aid In Metastatic Colorectal Cancer

Liquid biopsy following resection of colorectal liver metastases allows non-invasive molecular profiling which may help spot hard-to-detect remaining disease, according to Houston-based researchers.

Dr. Yun Shin Chun told Reuters Health by email that analysis of circulating tumor DNA "also termed liquid biopsy, has the potential to detect minimal residual disease, genotype tumors to direct targeted therapy, and track tumor evolution in real-time. Liquid biopsy is obtained via a simple blood draw, unlike tissue biopsy which requires a percutaneous or endoscopic procedure."

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Dr. Chun and colleagues at The University of Texas MD Anderson Cancer Center examined data from plasma drawn postoperatively from 63 patients who underwent resection of colorectal liver metastases. The researchers then used next-generation sequencing analysis to detect somatic mutations in 70 genes.

The most common mutation was APC, followed by TP53 and KRAS, they report in the Journal of the American College of Surgeons.

This approach, said Dr. Chun, was used in association with conventional methods to detect colorectal cancer, "specifically CT imaging and the tumor marker, CEA. The study results demonstrate that a positive liquid biopsy after surgery is associated with worse survival, particularly when 4 or more gene mutations are detected."

In particular, the team found that two-year overall survival from the date of liver resection was lower among patients with a positive liquid biopsy compared with those without such findings (70% vs. 100%, P=0.005).

In patients with four or more mutations, two-year survival was 41%. A positive liquid biopsy, but not elevated CEA, correlated with disease recurrence on CT scans.

Dr. Chun cautioned, "An important limitation of liquid biopsy for use in clinical practice is false-positive results. In this study, four patients had liquid biopsy samples with a single gene mutation that was not identified in tumor tissue. False-positive liquid biopsy results can result from a phenomenon known as clonal hematopoiesis of indeterminate potential (CHIP), which leads to gene mutations in the blood stream related to aging and not cancer."

Thus, he added, "Liquid biopsy results with a single gene mutation not identified in tissue should be interpreted with caution. The data support continued investigation of liquid biopsies in metastatic colorectal cancer for non-invasive molecular profiling and to direct targeted therapies, screen for clinical trials, and detect minimal residual disease."

In addition, "Liquid biopsy results can be used to counsel patients on adjuvant chemotherapy after surgery and to determine the extent and frequency of postoperative surveillance. In patients with no cancer identified on CT scans after surgery, a positive liquid biopsy may signal the need for additional imaging, such as PET scan, or closer follow-up."

—David Douglas

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