Circulating tumor DNA (ctDNA), a genetic material shed from tumors into the bloodstream, may identify patients with stage II colon cancer who may benefit most from chemotherapy after surgery and other patients with this type of cancer. May relieve the need for treatment, as demonstrated by a research study. Johns Hopkins Kimmel Cancer Center.
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A multi-institutional, international study led by researchers from the Johns Hopkins Kimmel Cancer Center and WEHI in Melbourne, Australia found that testing for ctDNA after surgery and directing chemotherapy to ctDNA-positive patients increased chemotherapy use without compromising recurrence. Reduced – free existence.
Several prior research studies demonstrate that circulating tumor DNA is detectable in the blood and that the presence of ctDNA after surgery predicts the risk of cancer recurrence. However, this is considered the first clinical study to show that measurement of circulating tumor DNA prior to therapy may benefit patients.
These findings will be published in the New England Journal of Medicine and presented June 4 at the annual meeting of the American Society of Clinical Oncology.
Burt Vogelstein, MD, Clayton Professor of Oncology, co-director of the Ludwig Center, says, “Previous studies have theorized that ctDNA measurement may be useful in guiding patient management, and this study is a real-world clinical clinical trial. provides evidence that supports these theories.” Johns Hopkins and Howard Hughes Medical Institute investigators. Vogelstein and group were the first to show that colon cancer is caused by a sequence of genetic mutations and showed that the DNA shed from tumors can be found in blood, feces and other body fluids.
Currently, the use of chemotherapy in stage II colon cancer, which is defined as colon cancer that has developed through the wall of the colon but has not spread to lymph nodes or other organs, is controversial. There is no consensus among cancer experts on its benefits. The aim of this study was to help resolve the controversy by assessing whether ctDNA could be used to provide a more accurate prediction of recurrence risk after surgery. ctDNA-negative patients could be shielded from the toxicity of chemotherapy, and those who had cancer remaining could receive chemotherapy to attack the malignant cells.
In the study, 455 patients with stage II colon cancer were randomized to standard treatment or ctDNA-guided management after surgery 2:1. Of these patients, 153 received standard management, which includes monitoring over time for recurrence or chemotherapy. An additional 302 patients were blood tested within seven weeks after surgery to look for ctDNA. If ctDNA was detected, patients received fluoropyrimidine or oxaliplatin-based chemotherapy. If ctDNA was not detected, patients did not receive chemotherapy.
The ctDNA-guided approach reduced the use of chemotherapy compared with the standard management group (15.3% of patients in the ctDNA-guided group received chemotherapy versus 27.9% in the standard management group). Two- and three-year survival without any cancer recurrence was similar between the ctDNA-guided group and the standard management group. “Stage II colon cancer presents a unique challenge,” Anne Marie Lennon, MBBCh., PhD, tells WebMD. Professor of Medicine, and Director of the Department of Gastroenterology and Hepatology.
“In stage I colon cancer, patients do not receive chemotherapy because their survival prognosis is greater than 90%. The risk of discomfort and toxicity from therapy outweighs the benefits it can provide. On the other hand, each stage III Colon cancer patient currently receiving chemotherapy because the risk of relapse is high.”
The goal of chemotherapy in colon cancer is to eradicate micrometastases, cancer cells that are not yet visible on radiological images that travel through the bloodstream and cause the cancer to come back or spread to other parts of the body. Detection of these invisible cells can now be used to identify which patients are most likely to have micrometastasis and, therefore, most likely to benefit from chemotherapy.
Joshua Cohen says, “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 clinical There is an opportunity to change the practice.” Lead author of the study and MD/Ph.D. candidate at the Johns Hopkins University School of Medicine.
The researchers hope that these findings will encourage the study of ctDNA in patients with other stages of colon cancer and other types of cancer. In future studies, the researchers will explore patients with early-stage pancreatic cancer and stage III colon cancer to see if ctDNA can identify patients who are most likely to benefit from the more aggressive chemotherapy currently used. Chances are. They also plan to explore whether the presence of residual ctDNA can be used to help optimize the management of individual patients after surgery or other types of therapy.
Using ctDNA to stratify treatments among patients is part of the movement towards precision medicine – personalized care that tailors treatments to the unique characteristics of cancer. The researchers also hope the findings will provide opportunities to test new drugs in patients who had earlier stage cancers.
Vogelstein says, “All drugs work better in patients with cancer who are detected relatively early, before they give rise to a large metastatic mass. However, newer drugs are usually tested in patients who are not whose cancer is very advanced.” “We hope that ctDNA analysis will enable the testing of new drugs in patients with early-stage cancer and micrometastases, when new drugs are most likely to save lives.”