Liquid Biopsies in the NSCLC Molecular Testing Algorithm

Martin Dietrich, MD: [Turning to] the structure, I know this isn’t what the guidelines recommend. They still de-emphasize liquid testing—more in a second—and reflex testing with some exclusions. In a real-world setting, there are so many obstacles to obtaining appropriate tissue at the time of first visit that it’s just a simple clinical requirement for us to have the information as soon as possible. Liquid biopsy has filled in very nicely and has become a cornerstone of diagnostic [testing] up front.

Benjamin Levy, MD: Yes, I agree. We’ll get Tim’s perspective on tissue, but I want to touch on liquid and get some perspectives around the room. Tim, what are your thoughts on how you incorporate ctDNA [circulating tumor DNA] in the diagnostic algorithm for patients? Then I want to get Fernando’s view on what’s done at Memorial [Sloan Kettering Cancer Center].

Timothy Craig Allen, MD, JD: Liquid biopsy has come into its own from its origin a few years ago. It’s still correct to say that tissue is superior. But we have to yield to the practicalities of patients who are difficult to get tissue from, those who recur. Often, it’s very difficult to get tissue, and those are good candidates for liquid biopsy. Some folks are doing liquid biopsy at the time of tissue biopsy and work-up because they’ll get a faster turnaround on the liquid. The tissue comes later with the results from the tissue molecular diagnostics that can help supplement the liquid biopsy results.

Benjamin Levy, MD: Hatim, what’s your perspective on how to incorporate liquid biopsies at UCSD [University of California San Diego] and how you’re using it in the diagnostic algorithm?

Hatim Husain, MD: Thank you, Ben. Tim gave a wonderful answer. To add to it, I’ll say that we do liquid biopsy up front. We think liquid biopsy is an essential component of diagnostic testing, largely because of the turnaround time that can be achieved. With more sophisticated technologies, there’s good concordance from tissue to liquid. When there isn’t concordance, if we get a negative liquid test, we emphasize reflexing the tissue and not forgetting about the tissue as the gold standard.

Benjamin Levy, MD: I agree. A negative tells you nothing. The sensitivity of liquid is around 70%. You get a 30% false negative, and a positive essentially rolls in. But at Johns Hopkins we’ve bought into the algorithm and drunk the Kool-Aid of using liquid with tissue. Given the challenges of tissue, we can talk about it later in this section.

Fernando, how are you routinely using liquid at Memorial? Is it every patient? I know you have an in-house liquid test. You have MSK-IMPACT, the tissue test. How do you molecularly profile patients?

Fernando C. Santini, MD: We have 2 broad and very good panels: MSK-IMPACT, which is the tissue NGS [next-generation sequencing], and a smaller but still very broad panel, MSK-ACCESS, for NGS and ctDNA. Fortunately, it reflects every lung cancer histology. [For tissue testing], non–small cell lung cancer goes to MSK-IMPACT reflexively. At every new visit, we try to collect with MSK-ACCESS the ctDNA as well. We’re trying to do as well like the Idylla for ctDNA for EGFR and KRAS, which can sometimes be even 1 day or a few hours in turnaround time. With a good amount of patients, we can start treatment fast with the Idylla ctDNA, where it’s complementary. We’re trying to do both platforms in the first visit.

Benjamin Levy, MD: All of us have started to do this. I want to reserve the challenges of tissue for the end, not only in the academic setting but in the community setting as well. Maybe we can revisit liquid in the context of those challenges.

Transcript edited for clarity.