Advances in Targeted Therapies for Non-Small Cell Lung Cancer - Episode 10

Repeat Liquid and Tissue Biopsy Practices in mNSCLC

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Nurse Practitioner Lauren Welch and Dr Michelle Shiller explain if and when they would offer repeat liquid or tissue biopsies to a patient with mNSCLC, and discuss how often patients request “serial biopsies” for detecting treatment response and/or disease progression.

Joel Neal, MD, PhD: Along the same lines, Lauren, I know that oftentimes patients who get liquid biopsies will request follow-up liquid biopsies. Sometimes we can use those for serial monitoring, looking at the percentage of tumor DNA in their blood as a surrogate for what's going on in their responses, there are many companies doing that. Do your patients request that? Do you offer that routinely, or do you save that for the point of recurrence when we're looking for changes after targeted therapy?

Lauren Welch, MSN, NP-C, AOCNP: I wouldn't say it's used routinely, but we do often use it if, say we got imaging and there was an indeterminate lesion or something was questionable, or maybe there was some signs of maybe indolent progression, sometimes we will repeat plasma or liquid biopsy at that point just to see is the ctDNA percentage increasing? Is something else emerging along with it to suggest more mutations are coming onboard, the cancer is starting to progress? But we don't use it routinely, occasionally, patients will request it, but most of the time we're introducing them to liquid biopsy for the first time, they're not coming in requesting it.

Joel Neal, MD, PhD: Our patients sometimes will ask for CEAs and serial repeat biopsies and even PET scans every six weeks instead of regular CT scans, and I think all of those are surrogates for earlier markers of progression. But the bottom line is if the tumor isn't growing and causing new mass effect, generally, patients with metastatic lung cancer still feel OK unless it's getting bigger. So, the CT growth is what I use for the treatment decision. And then Michelle, just on that point of, we'll get into a little bit later, but repeat biopsy, how do you get conveyed whether this tumor specimen coming in is an initial specimen or a repeat biopsy specimen, for tissue, of course, not liquid.

S. Michelle Shiller, DO, AP/CP, MGP: Right. I really love that question. I only usually know if we have previously tested the specimen. Do we look to see if we've previously tested the specimen every time, we sign a case out? Yes, we do look to make sure. And we will draw that together, for example, I recently had a case where the patient was treatment-naive, now they've seen some treatment, and while they still don't have a significant driver, they are acquiring more mutations being on chemotherapy which is something we will see. And so, it's not really even immune-active, but I do think that over time, they will meet that TMB benchmark that we have or have increased PD-L1 expression just based on the nature of what we understand there. Again, if I don't know that, but say I'm detecting a resistance mutation, for example, then I'm likely to call, not the pathologist per se, I may have to call the pathologist to get to the provider and try to track down who the provider is to get that clinical history. When I have that clinical history, I love it, and I will bring that out. We have a clinical genomic pathology consultation where we bring together everything we see, and I will definitely applaud that when I have it. So, I'd love to see what you have to say about liquid biopsy, but that is one area where I will say we are a little more in the dark on what is going on in that space when there may be simultaneous tissue testing occurring.

Joel Neal, MD, PhD: I think for liquid biopsy, most of the forms ask if the patient is newly diagnosed or previously treated, and they say what previous treatments did they have. I don't usually fill out those forms personally, we have a fantastic team who fills it out on my behalf, and I sign those forms and give them a quick glance, but they actually do get that information. Unlike the pathologist for tumor tissue where the repeat biopsy has to go through some sort of proceduralist first, interventional radiologist or pulmonologist oftentimes on their way to pathology. So, we've gotten to the point where we put a pathology order directly into our ordering system in addition to the referral for the procedure and then put on both of them "please refer to this path order, this is exactly what we want", but it's taken years to do and we're constantly improving the orders from the ordering side, just to make it obvious what to do.