fragments of tumor DNA in the blood may help identify the risk of recurrence of colorectal cancer -
Ludwig researchers working in collaboration with colleagues in Australia and the United States States have shown that tumor DNA fragments circulating in the blood can be used to assess the risk of colorectal cancer recurrence and the efficacy of chemotherapy following surgery. The discovery, published today in the current issue of Science Translational Medicine , is an important step towards developing a non-invasive and effective test for the detection, monitoring and treatment Cancer.
"Previous studies, including our group, have shown that this technique is sensitive enough to detect tumor DNA fragments in patients with advanced cancer," Bert Vogelstein, co-director the Ludwig Center at Johns Hopkins and one of the leaders of the study. "But this new study brings us a big step closer to the real purpose, because it suggests that it can detect residual disease in patients at an early stage, long before conventional clinical or radiological criteria can."
The decision of whether a stage II colon cancer patients should be treated with adjuvant, or post-surgery, chemotherapy remains one of the most difficult areas in colorectal oncology. These assessments are being made by combining a number of clinical and pathological features - such as the appearance of the tumor under the microscope, including how far it has spread through the wall of the intestine - or looking for presence of specific genetic markers of cancer that have prognostic significance.
However, current methods are inaccurate, and therefore doctors tend to err on the side of caution. Currently, up to 40 percent of stage II patients undergo the rigors and risks of adjuvant chemotherapy, although only a small fraction of them are for a relapse of cancer.
"The routine procedure is to give six months of chemotherapy, but we have no way of knowing whether the treatment is effective," said Jeanne Tie, an investigator with the Ludwig Institute and Walter Eliza hall of Medical Research (WEHI) in Victoria, Australia, and lead author of the study.
cancer cells often shed their DNA in the blood when they die, and recent technological advances have capture and profile of these relatively rare fragments of DNA. mutations in the tumor DNA circulating (ctDNA) can serve as highly specific biomarkers of cancer.
"We must be able to choose a DNA single tumor among ten thousand fragments of DNA normal, "said Tie." This is the sensitivity that we needed to come down to, and it has not been possible until now. "
for the current study, Tie and colleagues collected samples of tumors from 230 patients with stage II colorectal cancer. They analyzed the DNA of tumor samples and customized tests designed to target particular genetic mutations of each patient.
The tests were applied to blood samples taken from patients four to 10 weeks after surgery to remove tumors. Twenty of the 230 patients who tested positive for ctDNA, and of that group, 80 percent experienced a cancer recurrence in about two years. Of the 164 patients whose blood tested negative for ctDNA, only 10 percent relapse.
"A positive ctDNA test is an indicator that cancer cells from the original tumor are hiding somewhere in the body," said Peter Gibbs, a researcher at Ludwig WEHI who co-directed the study with Tie and Vogelstein.
the team also investigated whether ctDNA could be used to assess the impact of chemotherapy. Six tested positive patients ctDNA after surgery also underwent adjuvant chemotherapy. Scientists have continued to collect blood samples from these patients and found that in two patients, ctDNA readings changed from positive after surgery to negative after chemotherapy.
"In an oncologist, who is probably the most exciting one screening test ctDNA appearance - it can be used not only to determine the risk of recurrence, but also as a real-time marker chemotherapy benefit, "said Gibbs
in the present study, the tests were ctDNA CUSTOM-. tailored to the unique cancerous mutations in each patient, but scientists are also developing a test that ctDNA frequently covers occurring mutations of colorectal cancer.
"When such a generic test is developed, it could still take more than 0 percent of colorectal cancers, and it would eliminate the need to recover and test samples of individual tumors, saving time, effort and money, "said Gibbs.
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