A new study from the University of Washington School of Medicine in St. Louis points out that a liquid biopsy that examines blood or urine can help quantify the effectiveness of treatment for colorectal cancer that has just begun to spread beyond the original tumor. Such a biopsy can detect lingering disease and may be a guide for deciding whether a patient should receive further treatments as a result of some tumor cells avoiding an initial attempt to transplant cancer.
The study will appear online Feb. 12 in the Journal of Precision Oncology Clinical Oncology, a journal of the American Society of Clinical Oncology.
Although a few liquid biopsies have been approved by the Food and Drug Administration, mostly for lung, breast, ovarian and prostate cancers, none have been approved for colorectal cancer.
The patients in this study were called oligometastatic colorectal cancer, meaning that each patient’s cancers had spread beyond his original tumor but only to a small number of sites. Such patients receive chemotherapy to reduce the tumors before surgery is performed to remove the remnants of the primary tumor. There is debate in the field as to whether, after initial treatment, oligometastatic cancer should be treated as metastatic cancer, with more chemotherapy – or as local cancer, with more surgery in addition to radiation at these restricted sites.
Adding to the problem is the doctors ’limited ability to predict how patients respond to early chemotherapy, especially since most patients do not have access to the cancer genome genome to identify the DNA mutations in the their original tumors.
“Measuring response to early chemotherapy without prior knowledge of tumor mutations is an innovative idea and important for being able to determine if the patient has responded well to it. the cure, “said lead author Aadel A. Chaudhuri, MD, PhD, assistant professor of radiation oncology. “This can provide guidance on how to treat oligometastatic disease. For example, if the vascular biopsy reveals that a patient responded well to early chemotherapy, they may need to be given more surgery, But if they did not respond well, it is likely that the cancer is too widespread and cannot be eradicated by surgery, so patients should That’s more chemotherapy to control their disease. “
Liquid biopsies for colorectal cancer look for tumor DNA that has broken free of the cancer and is circulating in the blood and, to a lesser extent, accumulated in the urine. The biopsies described in this study are unique compared to other liquid biopsies being developed for colorectal cancer in three main ways. Initially, most such biopsies were developed to monitor for metastatic cancers or to confirm that local cancers have not begun to spread. Second, most fluid biopsies for cancer rely on knowledge of the mutations of the original tumor, to see if these mutations are still present in the blood after treatment. But many patients do not get a chance to have their original tumors ordered. Instead, the new biopsies are responsible for detecting DNA mutations in the blood or urine and comparing them with DNA mutations measured in the treated primary tumor, after surgically removed. . And finally, the urine biopsy is unique for colorectal cancer because most urine biopsies have been restricted in cancers of the genitourinary system, especially bladder cancer.
“The levels of circulating tumor DNA that we were able to measure in urine were lower than what we measured in blood, but this still confirms the notion that it able to quantify infectious disease in malignant cancers in this completely unconventional way, ”said Chaudhuri, who also treats patients at the Siteman Cancer Center at Barnes-Jewish Hospital and the University of Washington School of Medicine. “We need to develop more sensitive ways to detect colorectal tumor DNA in urine to make this a useful clinical trial. But this is a promising start.”
The study showed that lower circulating tumor DNA levels were associated with better responses to early chemotherapy. In fact, most patients who had levels of tumor DNA in blood samples in their surgical samples did not have measurable cancer.
There was also evidence that the residual disease detected in liquid biopsies was more predictable in the results than the infectious disease detected in the surgical samples. For example, the researchers described the experience of one man who, after early chemotherapy to reduce or eliminate the tumor, had yet to remove visible cancer during surgery. But his blood sample taken that day did not show circulating tumor DNA. He experienced long-term survival without cancer recurrence. On the other hand, a woman who did not have recognizable cancer cells in her surgical sample, which was removed after early chemotherapy, was found to have circulating tumor DNA in her blood sample the same way. day. Eight months later, the cancer returned to his liver.
The study suggests that such liquid biopsies may help with personalized treatment for oligometastatic colorectal cancer. In addition to identifying patients at risk of relapse and helping to guide decisions about what traditional treatments should be prescribed, the new study also identified patients who were at risk of relapse. could benefit from immunosuppressive and other targeted therapies.
“Based on mutations in the blood biopsy, we were able to identify patients who could benefit from a type of immunotherapy called immune checkups after their first treatment was completed,” Chaudhuri said. . “We also found mutations that could be targeted by drugs approved for other cancers. Our current study is observational, but it is a way to design future clinical trials that could test some of these treatments. “
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The study’s first co-authors are Bruna Pellini, MD, who did the work while a medical oncology associate at the University of Washington and is now with the Moffitt Cancer Center in Tampa, Fla .; Nadja Pejovic, visiting medical student in Chaudhuri laboratory; and Wenjia Feng, research assistant in radiation oncology.
This work was supported by the National Cancer Institute (NCI) of the National Institutes of Health (NIH) under award number K08CA238711; NCI Career Development Program P50CA196510; Cancer Research Foundation Young Inspector Award; Foundation Federation of American Society of Surgeons; American Cancer Society Institute Review Grant; James Ewing Foundation Clinical Examiner Award; Sidney Kimmel Translation Science Scholar Award; and the David Riebel Cancer Research Fund.
Chaudhuri serves as a scientific advisor / consultant and has received speaker honoraria, travel support and research support from Roche Sequencing Solutions, which was a series platform used in this study.
Pellini et al. detection of MRD ctDNA and oncogenomic personal examination in colorectal oligometastatic cancer from plasma and urine. Oncology Precision JCO. February 12, 2021.
The 1,500 faculty physicians of the University of Washington School of Medicine are also medical staff at Barnes-Jewish and St. Louis Children’s hospitals. Louis. The School of Medicine is a leader in medical research, teaching and patient care, ranking among the top 10 medical schools in the country by US News & World Report. Through its links with Barnes-Jewish and St. Louis Children’s Hospitals, the School of Medicine is affiliated with BJC HealthCare.
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