JUNE 4, 2022, NEW YORK – A Ludwig Cancer Research study has demonstrated that circulating tumor DNA (ctDNA)—which is shed from tumors into the bloodstream—can identify stage II colon cancer patients most likely to benefit from chemotherapy and help others avoid unnecessary treatment. Reported in the current issue of the New England Journal of Medicine and presented today at the Annual Meeting of the American Society of Clinical Oncology, the study found that testing for ctDNA after surgery and directing chemotherapy only to ctDNA-positive patients reduced chemotherapy use overall without compromising recurrence-free survival.
The research stems from a five-year, $10 million program that was supported by the Conrad N. Hilton Foundation and Ludwig Cancer Research for the prevention and early detection of colon cancer.
The clinical trial—led by physicians and scientists at Ludwig Johns Hopkins, their colleagues at Johns Hopkins University and Ludwig alumni at WEHI, in Melbourne, Australia—sought to determine whether ctDNA measurement could be used to predict recurrence risk after surgery for stage II colon cancer and settle a controversy about the utility of post-surgical chemotherapy for these patients. Researchers enrolled 455 patients with stage II colon cancer who were randomized after surgery, with 153 receiving standard care—which includes monitoring for recurrence—and 302 receiving blood tests for ctDNA within seven weeks following surgery. Patients in this group received fluoropyrimidine or oxaliplatin-based chemotherapy only if ctDNA was detected in their blood.
ctDNA monitoring reduced the use of chemotherapy: 15.3% of patients in the ctDNA-guided group received such therapy, versus 27.9% in the standard management group. Rates of two and three-year survival without recurrence were similar in the two groups.
This study shows ctDNA can identify which patients are most likely have micrometastases, which are difficult to detect radiologically and can seed recurrence. These patients are most likely to benefit from chemotherapy.
“Using ctDNA to guide treatment, a stage II colon cancer patient who is negative for ctDNA has a lower chance of cancer recurrence than the average stage I colon cancer patient, so we have an opportunity to change clinical practice,” said Joshua Cohen, an investigator at the Ludwig Center at Johns Hopkins who is an MD/PhD student at Johns Hopkins and a lead author of the study.
The researchers also believe their findings will provide opportunities to test promising new drugs in patients with earlier stages of cancer.
“All drugs work better in patients with cancers that are detected relatively early, before they have given rise to large metastatic masses,” said Bert Vogelstein, among the leaders of the study and the co-director of the Ludwig Center at Johns Hopkins University, Clayton Professor of Oncology at Johns Hopkins University and Howard Hughes Medical Institute investigator. “However, new drugs are usually first tested in patients whose cancers are very advanced. We hope that ctDNA analysis will enable testing of new drugs in patients with early-stage cancers and micrometastases, when the new drugs are most likely to save lives.”
The Johns Hopkins Kimmel Cancer Center press release from which this summary is derived can be found here.