A genetic blood test that spots bits of colon cancer-related DNA can help predict recurrence of the disease in some patients.
If the findings are confirmed by further research, the test could eventually help clinicians decide which patients need additional treatment after surgery for stage 2 cancer, researchers say.
Stage 2 tumors, in general, have invaded nearby tissues but have not yet spread to other organs and doctors don’t know for sure when chemotherapy after surgery is beneficial.
“Most patients with stage 2 colon cancers will be cured of the disease after surgery alone,” says Bert Vogelstein, professor of oncology at Johns Hopkins University School of Medicine.
“However, some of these cancers will recur, and we need to improve our diagnostic approaches to detect recurrence earlier than it can be found with current conventional methods.” Labs worldwide are working on DNA-based tests.
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For the study, published in the journal Science Translational Medicine, scientists followed 230 stage-2 colon cancer patients in 13 hospitals in Australia for four years, taking more than 1,000 blood samples. They also identified at least one colon cancer-related gene mutation in the tumor taken from each patient.
Over the next two years, they tracked each patient’s cancer-related mutation in periodic blood samples. The tracking used highly sensitive genetic tests to locate and amplify DNA found in the blood. Patients also underwent a CT scan of their entire body every six months after surgery for two years.
Among the 230 patients, 20 had cancer-linked DNA fragments in their blood, including 14 who did not receive chemotherapy and six who did. Of the 14, 11 developed a recurrence, found on a CT scan, during the study. Of the six who received additional chemotherapy, three experienced a recurrence during the study period. An additional 14 patients experienced cancer recurrences, but their blood tests had shown no cancer- linked DNA.
Predicting risk
“Although this and other DNA-based blood tests are not perfect, this study shows that when we find tumor DNA circulating in the blood of cancer patients, recurrence is very likely,” says Nickolas Papadopoulos, professor of oncology.
Currently, 40 percent of patients with stage 2 colon cancers are considered at risk for recurrence, based on measurements of how far cancer has grown into the intestine’s wall, the number of lymph nodes examined during surgery, and whether the cancer has spread to blood or lymphatic vessels. Those at higher risk usually get chemotherapy after surgery, but efforts to demonstrate its benefit have been hampered by the lack of large-scale studies.
Vogelstein says better methods to predict risk for recurrence, such as the blood test, could identify a very-high-risk subset of patients who can form the basis of rigorous study of the benefit of additional treatment.
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“There is mounting evidence that ctDNA is a viable approach for earlier detection of cancer recurrence, and more research is underway to refine the technology, improve its sensitivity and determine the best testing intervals,” says Kenneth Kinzler, co-director with Vogelstein of the Ludwig Center at the Johns Hopkins Kimmel Cancer Center.
There are no DNA-based blood tests for cancer now approved by the Food and Drug Administration, although several biotechnology companies are designing and studying them. Costs of the tests are estimated to range in the many hundreds to thousands of dollars, and it is unclear if health insurance companies would pay.
Kinzler, Papadopoulos, Vogelstein, and Luis Diaz, also of Johns Hopkins, are founders of PapGene Inc. and Personal Genome Diagnostics Inc., and members of the scientific advisory boards of Morphotek and Sysmex-Inostics. These companies and others have licensed patent applications on genetic technologies from Johns Hopkins, some of which result in royalty payments to Kinzler, Papadopoulos, Diaz, Vogelstein, and Isaac Kinde. The terms of these arrangements are being managed by the Johns Hopkins University in accordance with its conflict of interest policies.
Additional collaborators are from the University of Melbourne; Monash University; Eastern Health; Alfred Hospital; Warrnambool Hospital; the University of Adelaide; Ludwig Cancer Research; and Johns Hopkins.
Ludwig Cancer Research, the Conrad N. Hilton Foundation, the Sol Goldman Sequencing Facility at Johns Hopkins, the National Cancer Institute, and the Victorian Cancer Agency funded the work.
Source: Johns Hopkins University
