Role of Liquid Biopsies Continues to Evolve in GI Cancers

Ryan B. Corcoran, MD, PhD

Liquid biopsies can potentially offer a more precise snapshot of a patient’s tumor, but there are some limitations that have to be addressed before this strategy becomes more widespread in the gastrointestinal (GI) cancer paradigm, said Ryan B. Corcoran, MD, PhD.

This biopsy approach may miss molecular alterations with protein or RNA changes, Corcoran explained, adding that some patients do not shed enough tumor DNA to capture the tumor heterogeneity.

“Down the road, we hope that liquid biopsies can be used as an early-detection method. If we can identify patients with early-stage disease in a readily available manner, they will have a higher chance of being cured,” said Corcoran, who is a clinical researcher at Massachusetts General Hospital and an assistant professor of Medicine at Harvard Medical School.

OncLive: What is the role of liquid biopsies in GI cancer?

What are the pros and cons of using liquid biopsies in this setting?

In an interview with OncLive, Corcoran discussed the clinical utility and benefits of liquid biopsies in GI cancer.Corcoran: There are several emerging uses for liquid biopsies in GI cancers. Primarily, in clinical use, a liquid biopsy is used as a genotyping platform. This can be done both to assess for actionable mutations and alterations when a tissue biopsy is either insufficient or too dangerous to perform. There is a growing role for doing additional genotyping in parallel to a liquid biopsy, and after progression on first- and second-line therapy, this can be used to sequence additional therapies.One of the biggest positives of using a liquid biopsy is to perform genotype testing on the tumor in a minimally invasive manner. This allows us to observe how the tumor genome is evolving throughout treatment. One of the other advantages is that a liquid biopsy can perhaps better capture the tumor heterogeneity, and what I mean by that is, different tumor cells residing in different lesions or parts of the same lesion. These [cells] can develop different molecular mechanisms that can be clinically relevant. While a tissue biopsy can give you a limited catalogue of that, a liquid biopsy does this more expansively.

What data did you highlight at the 2nd Annual Precision Medicine Through Plasma: Using Liquid Biopsies in Contemporary Oncology Care?

Where is future research heading in this space?

What does the future have in store for liquid biopsies in GI cancer?

Some of the disadvantages of a liquid biopsy include that, by definition, cell-free DNA may miss molecular alterations involving protein or RNA changes. Sometimes patients simply do not shed enough tumor DNA and a liquid biopsy result can be unrevealing, even in the presence of disease.I spoke specifically about using a liquid biopsy to monitor resistance to therapy and to understand the tumor heterogeneity that can result during select therapy. How can we use this information to select the best sequential therapy? I also spoke about the emerging applications of liquid biopsies and how we can use them to salvage cure in patients who are not cured with surgery alone. I mentioned 2 specific clinical trials that will open in the next couple of months. They will be among the first in GI cancers to utilize cell-free DNA as a determinant of whether patients should receive additional therapy after surgery.A lot of the genotyping platforms have been optimized for targeted therapies, and with the emerging importance of immunotherapy, the genes covered need to evolve to be more optimal for that. Using liquid biopsies for real-time treatment monitoring can transform how we treat early disease.Some of the exciting potential applications for liquid biopsies are those that are on the horizon. Down the road, we hope that liquid biopsies can be used as an early-detection method. If we can identify patients with early-stage disease in a readily available manner, they will have a higher chance of being cured. This could transform the way we treat patients with cancer.

Another promising application of a liquid biopsy is to help us manage the perioperative phase of a patient with early-stage disease, specifically to detect for residual disease immediately after surgery. To elaborate on that, the only way we cure most solid tumors is by surgically removing all of the remaining cancer cells. A percentage of patients will have subclinical spread of cancer cells to other sites.

Unfortunately, we do not know about this until years down the line when that cancer recurs. However, liquid biopsies are emerging as a method to allow us with high fidelity to detect the patients with those so-called undetectable cancer cells. We could base treatment off that [knowledge]. We are seeing the first clinical trials underway addressing that question.

However, many of the future applications of liquid biopsies require validation in clinical trials. Certainly, as a means of using them to detect postoperative disease, the pivotal clinical trials are now taking shape. Before we can use a liquid biopsy in that setting, we need a feel for how it performs. The other challenge is access and reimbursement. Liquid biopsies are complicated and somewhat expensive. Improving their utility in these uses will make it more broadly accessible.