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Detection of Circulating Tumor DNA Predicts Colon Cancer Recurrence

By LabMedica International staff writers
Posted on 18 Jul 2016
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Image: An invasive adenocarcinoma (the most common type of colorectal cancer). The cancerous cells are seen in the center and at the bottom right of the image (blue). Near normal colon-lining cells are seen at the top right of the image (Photo courtesy of Wikimedia Commons).
Image: An invasive adenocarcinoma (the most common type of colorectal cancer). The cancerous cells are seen in the center and at the bottom right of the image (blue). Near normal colon-lining cells are seen at the top right of the image (Photo courtesy of Wikimedia Commons).
A team of American and Australian cancer researchers has demonstrated that circulating fragments of tumor DNA (ctDNA) could serve as a biomarker for identifying patients with high risk of recurrence of colon cancer.

Stage II colon cancer, which has spread through the wall of the colon but has not metastasized to the lymph nodes, can present a therapeutic dilemma. On one hand, these tumors can usually be completely removed by surgery, and the majority does not recur even without chemotherapy. On the other hand, it is difficult to determine which of these tumors will recur and to identify patients who would benefit from adjuvant chemotherapy after surgery.

To fill this diagnostic gap, investigators at Johns Hopkins University (Baltimore, MD, USA), the Ludwig Institute for Cancer Research (Baltimore, MD, USA) and the Walter and Eliza Hall Institute of Medical Research (Victoria, Australia) used massively parallel sequencing–based assays to evaluate the ability of ctDNA to detect minimal residual disease in 1046 plasma samples taken four to 10 weeks after surgery to remove tumors from a prospective cohort of 230 patients. The genomic assays were based on DNA isolated from each patient's tumor and targeted specific mutations.

The investigators reported that 20 of the 230 patients tested positive for ctDNA, and of this group, 80% experienced cancer relapse within about two years. Of the 164 patients whose blood tested negative for ctDNA, only 10% relapsed. A group of six patients who had tested positive for ctDNA following surgery also underwent adjuvant chemotherapy. In two of these patients, ctDNA disappeared following chemotherapy.

"A positive ctDNA test is an indicator that cancer cells from the original tumor are hiding somewhere in the body," said senior author Dr. Peter Gibbs, associate professor of medical oncology at the Walter and Eliza Hall Institute of Medical Research. "To an oncologist, that is probably the most exciting aspect of a ctDNA screening test - that it can be used not only to determine the risk of recurrence, but also as a real-time marker of chemotherapy benefits."

While results obtained in this study depended on ctDNA assays designed to detect each patient's unique cancer mutations, a ctDNA screening test is under development that will detect most frequently occurring colorectal cancer mutations. "When such a generic test is developed, it could still catch more than 90% of colorectal cancers, and it would eliminate the need to retrieve and test individual tumor samples, thus saving time, effort, and money," said Dr. Gibbs.

The study was published in the July 6, 2016, online edition of the journal Science Translational Medicine.

Related Links:
Johns Hopkins University
Ludwig Institute for Cancer Research
Walter and Eliza Hall Institute of Medical Research
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