Liquid biopsy for colorectal cancer could guide therapy for tumors

A new study from Washington University School of Medicine in St. Louis shows that a liquid biopsy examining blood or urine can help measure the effectiveness of therapy for colorectal cancer that has spread just outside the original tumor. Such a biopsy can detect persistent disease and could guide a decision as to whether a patient should undergo further treatment because some tumor cells are evading a first attempt to eradicate the cancer.

The study appears online Feb. 12 in the Journal of Clinical Oncology Precision Oncology, a journal of the American Society of Clinical Oncology.

While a few liquid biopsies have been approved by the Food and Drug Administration, mostly for lung, breast, ovarian, and prostate cancer, none have been approved for colorectal cancer.

Patients in this study had what is known as oligometastatic colorectal cancer, meaning that each patient’s cancers had spread beyond his or her original tumor, but only to a small number of locations. Such patients undergo chemotherapy to shrink the tumors before having surgery to remove the remnants 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 at those limited sites.

Contributing to the problem is that doctors have a limited ability to predict how patients will respond to early chemotherapy, especially since most patients do not have access to the genome of cancer to identify the DNA mutations in their original tumors.

“Being able to measure response to early chemotherapy without prior knowledge of tumor mutations is a new idea and important in determining whether the patient responded well to therapy,” said senior author Aadel A. Chaudhuri, MD, Ph.D . ., an assistant professor of radiation oncology. “This may provide guidance for the treatment of oligometastatic conditions. For example, if the liquid biopsy indicates that a patient responded well to the early chemotherapy, he may need to be given the option of more surgery, which could potentially cure his disease. did not respond well, it is likely that the cancer is too widespread and cannot be eradicated with surgery, so those patients should receive more chemotherapy to control their disease. “

Liquid colorectal cancer biopsies detect tumor DNA that has broken loose from the cancer and is circulating in the blood and to a lesser extent collected in the urine. The biopsies described in this study are unique in three main ways compared to other liquid biopsies being developed for colorectal cancer. First, most such biopsies are designed to detect metastatic cancers or to verify that local cancers have not spread. Second, most liquid cancer biopsies rely on knowledge of the tumor’s original mutations to see if those mutations are still present in the blood after therapy. But many patients are not given the opportunity to have their original tumors sequenced. Instead, the new biopsies rely on detecting DNA mutations in the blood or urine and comparing them to DNA mutations measured in the treated primary tumor after it has been surgically removed. 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 levels of circulating tumor DNA that we could measure in the urine were lower than what we measured in blood, but this is still a proof of concept that it is possible to measure residual disease in a non-urinary cancer in this totally non-invasive way, “said Chaudhuri, who also treats patients at the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine.” We will need to develop more sensitive techniques to detect colorectal tumor DNA in urine. to make this a useful clinical test. But this is a very promising start. “

The study showed that lower circulating tumor DNA levels correlated with better responses to early chemotherapy. Indeed, most patients who had undetectable levels of tumor DNA in blood samples also had no measurable cancer in their surgical specimens.

There was also evidence that the residual disease detected in liquid biopsies was more predictive of outcomes than the residual disease found in the surgical samples. For example, the researchers described the experience of a man who, after early chemotherapy to shrink or eliminate the tumor, had detectable cancer removed during surgery. But his blood sample taken that same day showed no circulating tumor DNA. He experienced long-term survival with no cancer recurrence. On the other hand, a woman with no detectable cancer cells in her surgical specimen, removed after early chemotherapy, was found to have circulating tumor DNA in her blood sample on the same day. Eight months later, the cancer returned to her liver.

The study suggests such liquid biopsies could help personalize oligometastatic colorectal cancer treatment. In addition to identifying patients at high risk of recurrence and helping guide decisions about which traditional therapies to give, the new study also identified patients who could benefit from immunotherapies and other targeted treatments.

“Based on mutations in the blood biopsy, we were able to identify patients who could benefit from a type of immunotherapy called immune checkpoint inhibitors after their first therapy is completed,” said Chaudhuri. “We also found mutations that could be targets of drugs approved for other cancers. Our current study is observational, but it paves the way for designing future clinical trials that can test some of these potential therapies.”

More information:
Pellini et al. CtDNA MRD detection and personalized oncogenomic analysis in oligometastatic colorectal cancer from plasma and urine. JCO precision oncologyFebruary 12, 2021.