Researchers see Liquid Biopsy for Colorectal Cancer Could Guide Tumor Treatment
A new study from the University of Washington School of Medicine in the United States has shown that a liquid biopsy that examines blood or urine can help measure the effectiveness of colorectal cancer therapy and could serve as a guide to decide whether a patient must undergo additional treatments.
In the study, published in the Journal of Clinical Oncology Precision Oncology, several patients with oligometastatic colorectal cancer were investigated, meaning that each patient’s cancers had spread beyond their original tumor, but only to a small number of sites.
These patients undergo chemotherapy to shrink the tumors before undergoing surgery to remove what is left of the primary tumor.
There is debate in the field as to whether, after initial therapy, oligometastatic cancer should be treated as metastatic cancer, with more chemotherapy, or as localized cancer, with more surgery plus radiation to those limited sites.
Currently, clinicians have limited ability to predict how patients will respond to early chemotherapy, especially since most patients do not have access to cancer genome sequencing to identify DNA mutations in their original tumors.
“Being able to measure response to early chemotherapy without prior knowledge of tumor mutations is an important new idea to be able to determine if the patient responded well to therapy. This may provide guidance on how to treat oligometastatic disease,” noted lead author Aadel A. Chaudhuri, assistant professor of radiation oncology.
Thus, he explains, “if the liquid biopsy indicates that a patient responded well to early chemotherapy, perhaps they should be offered the possibility of further surgery, which could potentially cure their disease. But if they did not respond well, it is likely that the Cancer is too widespread and cannot be eradicated with surgery, so these patients should receive more chemotherapy to control their disease.”
Liquid biopsies for colorectal cancer detect DNA from the tumor that has been released from the cancer and is circulating in the blood and, to a lesser extent, has accumulated in the urine.
The biopsies described in this study are unique compared to other liquid biopsies that are being developed for colorectal cancer in three main ways.
First, most of these biopsies have been developed to track metastatic cancers or to verify that local cancers have not started to spread.
Second, most liquid biopsies for cancer rely on knowing the mutations in the original tumor, to see if those mutations are still present in the blood after therapy. But many patients do not have the opportunity to sequence their original tumors.
The new biopsies are based on the detection of DNA mutations in the blood or urine and comparing them with the DNA mutations measured in the treated primary tumor, after surgical removal.
And finally, the urine biopsy is unique to colorectal cancer, as most urine biopsies have been limited to use in cancers of the genitourinary system, especially bladder cancer.
“The circulating tumor DNA levels that we were able to measure in the urine were lower than those we measured in the blood, but this is still proof of concept that it is possible to measure residual disease in non-urinary cancer in this totally non-urinary way. We will need to develop more sensitive techniques to detect DNA from colorectal tumors in urine for this to be a useful clinical test. But this is a promising start,” said Chaudhuri, who also treats patients at Siteman Cancer Center in the United States.
The study showed that lower levels of circulating tumor DNA correlate with better responses to early chemotherapy. In fact, most of the patients who had undetectable levels of tumor DNA in blood samples also did not have measurable cancer in their surgical samples.
There was also evidence that residual disease found in liquid biopsies was more predictive of results than residual disease found in surgical specimens.
For example, the researchers described the experience of a man who, after early chemotherapy to shrink or eliminate the tumor, still had a detectable cancer removed during surgery. But his blood sample taken that same day showed no circulating tumor DNA. He experienced long-term survival without cancer recurrence.
On the other hand, a woman with no detectable cancer cells in her surgical sample, drawn after early chemotherapy, was found to have circulating tumor DNA in her same-day blood sample. Eight months later, the cancer returned to his liver.
The study suggests that such liquid biopsies could help personalize treatment for oligometastatic colorectal cancer.
Beyond identifying patients at high risk of recurrence and helping guide decisions about which traditional therapies to administer, the new study also identified patients who could benefit from immune therapies and other targeted treatments.
“Based on the mutations in the blood biopsy, we were able to identify patients who might benefit from a type of immune therapy called immune checkpoint inhibitors after their initial therapy is complete. We also found mutations that could be targeted by drugs. approved for other cancers. Our current study is observational, but it paves the way to design future clinical trials that could test some of these potential therapies,” concludes Chaudhuri.
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