Expanding Targets in NSCLC - Episode 11

Tissue Conservation and Liquid Biopsies in NSCLC

Transcript: Edward B. Garon, MD: As a lung cancer doctor, I always find it interesting when I talk to my colleagues, for instance, in breast cancer. In breast cancer, the majority of women diagnosed have a surgery during the early part of their care. The availability of tissue is great, so these issues that we often have seem strange to them. Of course, in lung cancer, most patients are diagnosed at more advanced stages. And oftentimes, this is based on fairly limited tissue. I know when I started my training, just having a few cells that would be consistent with non—small cell lung cancer would have been sufficient. And particularly if it were in a site of metastatic disease, it would be sufficient to diagnose and stage the patient and get all the information that was necessary.

As we’ve learned more about the molecular drivers of lung cancer, it has been more important that we do test for these mutations; and there is need for greater analysis of tissue. Unfortunately, our amount of tissue that we obtain is not tremendously greater than it was. There are certainly academic centers used to research protocols that require larger biopsies, where we may be getting larger biopsies. But the lack of availability of tissue is a significant issue.

Many centers have worked very hard on this 1 thing that does become a complicated issue: Each time 1 goes into a block, you lose some of the tissue. So if the pathologist does a bunch of immunohistochemical stains, and then they put it away, and then they run 1 set of molecular studies, and they go in to get a second set of molecular studies, there also ends up being waste of a lot of tissue. That can be problematic. And so it is an issue that comes up, and it is part of what has motivated the enthusiasm for liquid biopsy as well in a disease like lung cancer, where it can be difficult to obtain enough tissue.

We definitely have patients in our practice who have been diagnosed with MET alterations, including MET exon 14 skipping, via a liquid biopsy. I think this can be an effective approach. I think that the important thing to recognize about a liquid biopsy is that the specificity is quite good. If you get a positive result, certainly, if the laboratory is good, your confidence in that result can be quite high.

The sensitivity is variable. Particularly in patients who may have a limited bulk of disease, there may be some issues with sensitivity, where you miss the result with a liquid biopsy. So I think that a liquid biopsy certainly can be helpful in terms of identifying these mutations, but at least in my practice, I am very reluctant to assume that a patient does not have one of these mutations just based on a negative liquid biopsy.

Transcript Edited for Clarity