While conducting the study, the scientists analysed 455 patients with stage II colon cancer who were randomized after surgery 2:1 to standard treatment or ctDNA-guided management.
Scientists at the Johns Hopkins Kimmel Cancer Center have found that circulating tumor DNA (ctDNA), a genetic material that is shed from tumors into the bloodstream, has the potential to identify stage II colon cancer patients who can most benefit from chemotherapy following surgery and spare other patients the need for this form of treatment. While conducting this multi-institutional and international study scientists found that testing for ctDNA after surgery and directing chemotherapy to ctDNA-positive patients reduces the use of chemotherapy overall without compromising recurrence-free survival. The findings of the study were published in the New England Journal of Medicine and presented at the annual meeting of the American Society of Clinical Oncology last week.
“Previous studies have theorized that ctDNA measurements might be useful in guiding patient management, and this study provides real-world clinical evidence that supports these theories,” says Bert Vogelstein, M.D., Clayton Professor of Oncology, co-director of the Ludwig Center at Johns Hopkins and a Howard Hughes Medical Institute investigator. Reportedly, Vogelstein and group were the first to show that colon cancer is caused due to a sequence of genetic mutations. They also showed that DNA shed from tumors could be detected in blood, stool and other body fluids.
According to the scientists, the study was aimed at helping solve the controversy by assessing whether ctDNA could be used to provide a more precise prediction of recurrence risk after surgery. Patients who were ctDNA-negative could be spared the toxicities of chemotherapy, and those who had remaining cancer could receive chemotherapy to attack the lingering malignant cells.
While conducting the study, the scientists analysed 455 patients with stage II colon cancer who were randomized after surgery 2:1 to standard treatment or ctDNA-guided management. Of these patients, 153 received standard management, which includes monitoring over time for recurrence or chemotherapy. An additional 302 patients underwent blood tests within seven weeks after surgery to search for ctDNA. If ctDNA was detected, patients received fluoropyrimidine or oxaliplatin-based chemotherapy. If ctDNA was not detected, patients did not receive chemotherapy.
The researchers are hopeful that these findings will stimulate the study of ctDNA in patients with other stages of colon cancer and other types of cancer. The scientists will plan to explore patients with early-stage pancreatic cancer and stage III colon cancer to see if ctDNA can similarly identify patients who are most likely to benefit from more aggressive chemotherapy than is currently used.
Using ctDNA to stratify treatments among patients is part of the movement toward precision medicine — individualized care that tailors therapies to the unique characteristics of a cancer. The researchers also believe the findings will provide opportunities to test promising new drugs in patients with earlier stages of cancer.