Right now, when we want to know everything we can about a tumor, we do surgery: a biopsy to take a sample of it and look at it under a microscope and determine as best we can how to treat it. But what if instead you could get a blood test, and learn even more. That’s the promise of the relatively new science of what is called cell free DNA (cfDNA). It holds the hope of helping us better understand cancer, its behavior in our bodies over time, and even offering clues on how to better treat cancer in ways we would never have imagined even a few short years ago.
It was an important area of discussion at the American Society of Clinical Oncology meeting this week. It’s a meeting where, every year, we get a sense of the future of cancer treatment before it becomes a reality. From genomics, to immunotherapy, to targeted therapies–you name it—promising areas appear on the scene, then either become part of our reality or lose luster as the process unfolds over the course of several ASCO annual meetings. This year, several studies presented on the topic of the so-called “liquid biopsy” illustrate how this new technology and science may very soon influence the way we care for people with cancer.
The technique is complicated to be certain, but in very simplified terms, it’s essentially taking a routine blood sample, isolating protein material from the blood, sorting out those proteins to select the relevant genetic material, then analyzing those proteins to get a genetic profile of the tumor by focusing on the specific DNA shed by the cancer. Then that DNA is analyzed by genomic sequencing to detect the genetic abnormalities that define the cancer in question.
Until now, we have had to take an actual biopsy of the cancer to get the same material. Although we can now do biopsies using smaller needles rather than actually having to cut into someone with a surgical procedure, the reality is that when we use a needle, we often don’t get enough material to do all the tests we would like, such as adequate genetic sequencing.
In addition, a genetic abnormality present in one part of a tumor may not be present in all parts of the cancer tumor, so a sample taken through surgery or a needle may miss important clues. And sometimes additional clues lie in distant lesions (metastases) if the cancer has spread; abnormalities that weren’t present in the tumor from which the biopsy is taken.
Finally, we are still uncertain how many times we need to rebiopsy a cancer over the course of treatment or when to rebiopsy to get the most accurate genetic information—information which may help us better understand why the cancer is growing and give us clues as to what the next treatment should be.
Now you can begin to understand the promise of liquid biopsies. And this year, we continued to discover how and under what circumstances cfDNA may be able to help us out.
For example, a study (whose lead author, incidentally, was Dr. Oliver Zill who in the past had received a research grant from the American Cancer Society) was presented from a company called Guardant Health which compared the cfDNA from about 15,000 patients with over 50 cancers to a standard “dictionary” of genetic changes called The Cancer Genome Atlas (TCGA) which includes biopsy-obtained tissue from about 9,000 patients with 27 cancers. Many of the patients in the Guardant study had advanced cancers, under treatment for almost a year after diagnosis and already on their second or greater treatment program.
The results were fascinating:
When it came to finding the “driver” (or fundamental) mutations that are essential to the development of cancer, the blood samples were positive on average 85% of the time for one of those mutations. And those mutations that were detected were almost identical to what had been found in the same cancers in the TCGA. That’s not perfect, but it is pretty remarkable.
On the other hand, when it came to the mutations that appeared as the cancer evolved, the relationship did not hold up quite as well when compared to the standard biopsy tissue analyses. So if a cancer developed a mutation along its journey—which would correlate with resistance to treatment and progression of the cancer—that might not show up as readily. This is probably because those resistance mutations appear later in the course of disease in lower volume/frequency. Over time, the science behind cfDNA will likely progress to be able to detect these changes more often.
All told, 49% of the patients assayed in this study had a genetic alteration that could be treated with an FDA approved cancer drug. That’s almost half. That means this approach has the possibility of guiding treatment in cancer patients in a substantial number of situations.
What is even more remarkable is that when resistance mutations—those mutations that signaled the cancer was progressing–were detected in the blood sample, 27% of the patients had what we call an “actionable event.” In plainer language, in about one in four cases, the information from the cfDNA analysis offered an opportunity to change treatment to a known drug that may help treat the cancer.
The big picture at this year’s ASCO: substantially more information about biomarkers that help us select the best treatment for a person’s cancer were found in the cfDNA than in the standard biopsy samples. Think of a traditional biopsy as a random shot: you grab one part of the cancer, from which and you may or may not get the information you need. On the other hand, cfDNA is like a vacuum cleaner bag: all the stuff from the whole house ends up in one place. You may not know where the DNA came from, but at least you were able to capture it.
This is science in progress. We still have a ways to go before this technology becomes a routine part of cancer care. But it probably isn’t going to be a long journey, as this technology and the science behind it is evolving rapidly. Our understanding of how to use that science doesn’t appear to be far behind.
I can’t imagine many of us who wouldn’t prefer a needle stick for blood to undergoing surgery to get a piece of cancer tissue which would help guide the treatments we receive, and also help us know when the cancer is responding to treatment—and when it is progressing.
We may not be there yet, but we aren’t far away.