It sounds like the stuff of science fiction.Cancerous tumors shed whole cells or tiny bits of DNA and other genetic material into the bloodstream and other bodily fluids. This allows clinicians to potentially analyze blood samples to detect a tumor's unique mutations and offer a personalized treatment regimen, all without an invasive tissue biopsy.
Science fiction is swiftly becoming reality according to Dr. Daniel Zimmerman, Senior Vice President and Chief Medical Director, Global Support Team for RGA. With a background in molecular biology and medical microbiology, Dr. Zimmerman is board-certified in internal medicine and pediatrics and has more than a decade of experience in insurance medicine. He makes the case in the interview below that liquid biopsies have the potential to transform clinical and insurance medicine by enhancing risk selection and potentially improving mortality and morbidity.
This post is the second in a two-part interview with Dr. Zimmerman based on his webinar “Epigenetics and Liquid Biopsies: Fact, Fiction or Both.” Read Part I and view the webinar here.
First, define “liquid biopsy.”
Liquid biopsies are noninvasive tests to detect and classify cancers by identifying the small amounts of genetic material that tumors shed into the bloodstream or other bodily fluids.
Start with a traditional biopsy. As underwriters or claims adjudicators know, the traditional diagnosis of cancer relies on a histopathological specimen. How is that obtained? First, a doctor has to physically perform a biopsy of a suspected tumor, either via needle or an open procedure. The specimen is then sent to a laboratory. Technicians there make many thin slices of this biopsied material, which are placed on a glass slide, stained, and viewed under the microscope by a pathologist.
In contrast, a liquid biopsy involves no surgery or invasive procedures, usually only a blood draw. There are two basic types. One tests for circulating tumor cells that break away or get separated from the main tumor mass. The second type detects DNA, RNA, or other materials that enter the bloodstream when a tumor cell breaks open and spills these contents.
Why is there so much buzz around liquid biopsies right now?
Performing a traditional biopsy involves surgery or an invasive procedure and therefore can have complications. For example, a lung biopsy could result in a collapsed lung or bleeding.
Science is always looking for a better way to screen, diagnose, and manage disease, and there is essentially little to no risk associated with a liquid biopsy. Also, liquid biopsies can be performed when there's not enough tissue available or that tissue is hard to reach.
So liquid biopsies are safer.
There are other advantages, too. Traditional biopsies present a one-time opportunity because they are so invasive: Rarely do doctors go back in and re-biopsy a tumor. In contrast, a liquid biopsy can be performed multiple times. Why is this important? Liquid biopsies address the problem of inadequate sampling size error. There are times when a physician biopsies a mass or tumor and only later determines that there were insufficient tumor tissues for a diagnosis.
Tumors also change over time, and so liquid biopsies allow physicians to monitor that evolution. Currently, for example, a cancer patient undergoes surveillance after treatment to look for recurrence; this may take the form of scans or other tests. If you could detect the DNA or other genetic products earlier from a recurrence or changes in a cancer as part of regular liquid biopsy tests, physicians could change or initiate treatment faster.
Liquid biopsies also address the problem of intra-tumor heterogeneity and assessing metastatic lesions. Basically, a tumor is a mass of cells, but all those cells are not the same; different cells can have quite different genetic variations. A single tissue sample collected for a traditional biopsy could miss important mutations with very different prognostic implications just millimeters away. By contrast, a liquid biopsy should reflect all the variation present. Similarly, metastatic lesions also have genetic differences and these can also be detected, theoretically, by liquid biopsies.
No wonder so many people are enthralled by the promise of liquid biopsies. What is hype and what is reality?
It’s important to keep a sense of balance. To evaluate any of these new tests, large groups of individuals will need to be evaluated through clinical studies. That’s going to take some time.