Part 1: Challenges in Performing Biopsies and Molecular Testing in NSCLC

Martin Dietrich, MD, PHD

DISCUSSION QUESTIONS

• Do you consider options such as next-generation sequencing [NGS], liquid biopsy, polymerase chain reaction testing, immunohistochemistry, or other options when testing a patient with late-stage lung cancer?
• What is the protocol at your center for lung cancer molecular testing? Do you order molecular panel testing for every patient with metastatic lung adenocarcinoma? If not, which patients are tested?
• For which genes do you order targeted tests upfront?
• Is PD-L1 testing a reflex test at your institution?How do you factor results into treatment planning? Are there other reflex test orders in place?

MARTIN DIETRICH, MD, PHD: How do you approach your lung cancer molecular testing?

LUIS RAEZ, MD: In general, we prefer to do NGS in liquid and tissue, and when we order the tissue, we also order the PD-L1 there. We order [tests] for both because that way we have the results much faster, since we get liquid in 8 or 9 days, but because they don’t give all the answers, we wait 3 more weeks for…tissue.

DIETRICH: I think that the combined up-front testing is becoming, rapidly, the standard for most settings.

JAY WANG, MD: We need to get a tissue diagnosis, and then, once we have the diagnosis of non–small cell lung cancer [NSCLC], then I’ll do the PD-L1 and NGS panel. I also do the liquid biopsy at the same time, to make sure we don’t miss any markers, and also due to the speed. So I do both, but we still need to get a tissue diagnosis. Without tissue diagnosis, I cannot order the liquid [biopsy].

TIM NGUYEN, MD: I do both. We do have a path that’s reflex testing in-house, but it’s mainly the ALK/VEGF [testing], so that’s the limit of what we do—and the PD-L1. But mostly, I send it out to the Foundation Medicine, or Caris Life Sciences, and liquid biopsy.

ROBERT KOCH, MD: I generally do the NGS sequencing and PD-L1 immunohistochemistry studies. I do not do liquid biopsy up front, unless I’m suspicious that NGS has missed something that I might be able to find on a liquid biopsy at a later date.

DIETRICH: That’s what the [current] guidelines would suggest, that you start with tissue and then use liquid as a fill-in.

DIMITRIOS AGALIOTIS, MD: I would say that you should try liquid biopsy first, and tissue after. Of course, you need to have your histological diagnosis. Plus, there are some markers that are not good for liquid biopsy. For PD-L1, they say you have to test because it’s matter of microenvironment of the tumor, as well.

DIETRICH: There are some circumstances where the liquid biopsy comes synchronously, or even first.

SUSHMA NAKKA, MD: I still don’t get enough tissue a lot of times. But I use both.

DISCUSSION QUESTIONS

• How often do you receive insufficient tissue test reports in your practice? What do you do in those situations?
• What can medical oncologists do to help ensure that sufficient tissue quantity is collected, and that tissue is used efficiently? What needs to be communicated to the interventionalist conducting the biopsy and the pathologist?

DIETRICH: Of the non-clinical barriers to testing, insufficient tissue is probably the biggest one. I think reimbursement has gotten a lot better. When you send 10 cases, what’s your insufficient tissue rate?

RAEZ: In our institution, it’s close to 20%.

NEERAJ SHARMA, MPH: I would just want to say the same thing, about 15% to 20%, something like that. You do bump into that issue from time to time.

HARSH AMIN, MD: I would say 20% to 25% insufficient tissue.

WANG: I see a lot higher, probably 30% to 40%.

JORGE HURTADO, MD: I would have to agree with Dr. Wang, it’s probably about 30% to 40%. We get a lot of non-diagnosis, unfortunately.

DIETRICH: Obviously, these communications to the proceduralists here are important; to pathology, to make sure that they understand that the tissue and [liquid] biopsy here are important, but the molecular testing gives us an equal amount of information. I think most people use the liquid biopsy and feel comfortable using it. The delayed results from tissue testing is another incentive to use liquid up front. I adopted it. Lung cancer has an urgency, so having both up front [offers] some sensitivity that doesn’t overlap, and there are also some advantages from a logistical standpoint. You’re not dependent on 14-day rules, and other factors that may be playing a role if you don’t have an in-house panel.

DISCUSSION QUESTIONS

• How often does a PD-L1 test come back before all remaining biomarkers? Do you start therapy before all results come back?
• Do you read the entire molecular test report or look for specific results? Do you look for ALK, ROS1, BRAF, NTRK1/2/3, MET exon 14 skipping, RET, KRAS or other rare mutations at this time?
• With so many biomarkers, how do you communicate with the pulmonologist, pathologist, interventional radiologist, et al, to make sure full array of recommended biomarkers are being evaluated?

DIETRICH: For most of us, PD-L1 is done in-house, so, it should come back earlier [than other biomarkers] for most of our tissues. Are there any specific results that you’re looking at, such as rare mutations? Do you do a full review? Do you do a molecular tumor board review for your cases? What is it you’re looking for in those results?

NGUYEN: [I review all] actionable mutations.

DIETRICH: All of them? You’re practicing at the Cleveland Clinic. Do you have a full panel for all the FDA-approved markers?

NGUYEN: Not in-house.

DIETRICH: Is there anybody who has an in-house panel for NGS? Do you mind me asking what reference lab you’re using when you’re sending out?

NAKKA: I use Onkotype MAP, and also FoundationOne for tissue.

KOCH: I use FoundationOne as well.

SHARMA: We use FoundationOne, and also some of these [tests] go to the hospital when they get the biopsy, then they use their preferred labs.

AGALIOTIS: The hospital uses NeoGenomics for us, but I use Caris and Foundation, or Guardant360, especially if we do both at the same time, because they do liquid and they do tissue as well.

DIETRICH: We don’t communicate [about addressing all biomarkers with those involved in testing]. All we ask them for is to be tissue-sparing, and to give us as much tissue as possible. The full array of biomarkers is sometimes hard to keep up for me, not to speak of the people that are providing and processing all that tissue. I think it’s important for them to understand how important it is, and that the molecular value is almost as high as the histological, sometimes even higher in the metastatic setting.