1. DiGiulio, Sarah

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Liquid biopsies are increasingly playing a role in oncology care, currently as prognostic tests. But researchers say they may at some point be useful in cancer diagnostics, too, although more research is needed before that is a reality. Leon Pappas, MD, PhD, Clinical Fellow in Medical Oncology at Dana-Farber Cancer Institute and Massachusetts General Cancer Center, and colleagues recently discussed the potential role of these tests in oncology in a Comment article in Nature Cancer (2022;

Leon Pappas, MD, PhD... - Click to enlarge in new windowLeon Pappas, MD, PhD. Leon Pappas, MD, PhD

"Mounting evidence of clinical benefit is now allowing both reimbursed and FDA-approved tests," they stated in the article, which goes on to discuss some key studies on the topic and the ongoing major trials. In an interview with Oncology Times, Pappas shared why this topic is important and that the oncology community should take note.


1 Let's start at the beginning: What exactly is a liquid biopsy?

"They are blood tests which isolate DNA that is floating within the blood. The DNA of cancer cells can be distinguished from the DNA of healthy cells with these tests and analyzed for DNA sequence changes (mutations) that can allow us to both tailor cancer-directed therapy and track responses to therapy by measuring the amount of cancer cell DNA circulating in the blood over time.


"To clarify, the utility of these tests currently is limited to patients with an existing cancer diagnosis. Newer assays are being actively developed to detect cancer cell DNA in people who do not have a current diagnosis of cancer, but none of these are yet good enough to be used broadly in the population.


"Liquid biopsies have been an emerging area of biomedical research for years, but have now gained an increasing role in the clinic in the management of patients with many different types of cancer. Given the multitude of clinical trials that have demonstrated the promise of these tests both in assisting earlier diagnosis and monitoring response to therapy-with many more clinical trials upcoming that are expected to solidify and expand the clinical utility of these tests-we felt it was a highly opportune time to review the most important recent discoveries in this space."


2 What are some advantages and disadvantages to liquid biopsies over other types of tests-both prognostic and potentially diagnostic?

"Currently, patients with an existing cancer diagnosis rely on imaging techniques (CT scans or MRIs) and tumor markers (blood tests) for the detection and monitoring of cancer progression and response to treatment. Current imaging has a limit of detection, which requires many million to a billion cancer cells to form a mass before they can be detected on scans. This is in contrast to the liquid biopsy techniques which can detect cancer when the cancer cells are orders of magnitude fewer and when they may not be able to be seen on scans.


"Traditional tumor markers are not very specific for cancer and can increase with inflammation-either from a disease or a procedure or infection. They are also not very sensitive tests, meaning that people can have cancer with masses visualized on scans, but still have normal tumor markers. This is not the case with circulating tumor DNA, which is more sensitive and specific than traditional tumor markers.


"We are still in the early days and the clinical utility and benefit of these technologies have not been assessed in sufficient studies to warrant formal broad recommendation for use across all cancers and stages in lieu of other studies. They are currently recommended as supplemental studies to traditional cancer monitoring with imaging and traditional tumor markers.


"It is possible that, in the future as these assays improve, they may reduce the frequency of use of traditional surveillance technologies, though this is still speculative. It is important to also point out that detection of cancer with liquid biopsies in a healthy population (i.e., people without cancer) is still too early to be used clinically and [its] investigational."


3 Is there anything more practicing oncologists and cancer care providers should know about this work or your work in this field?

"We think that providers should stay tuned on this area of research as we expect it to be a part of standard cancer care in the not-too-distant future. We are working with basic scientists who are designing more sensitive assays, one of whom is our co-author Dr. Viktor Adalsteinsson, and we are designing and implementing clinical trials that are using these assays both to monitor patients on treatment, as well as to understand how to best use these tests to decide the amount and type of treatment patients can receive."