Non–Small Cell Lung Cancer: Streamlining Turnaround Times in Biomarker Testing

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Transcript:

Charu Aggarwal, MD, MPH: Talking about turnaround times, I’ll just ask around the table. I'll start with you, Martin [Dietrich]. What is the average turnaround time for tissue results, and what factors are affecting it currently?

Martin Dietrich, MD, PhD: That’s a difficult question because there are so many channels to which patients and tissues are obtained that can sometimes go very fast. The average turnaround time for NGS [next-generation sequencing] is somewhere around 10 to 12 days if there are no other delays at the front end. But we certainly see patients that are being treated and biopsied at hospitals that still hold on to the 14-day rule, where sometimes turnaround time is more like 3 to 4 weeks.

So, I think on average, 2½ to 3 weeks is what most tissue-based tests have. I fully agree with you, that liquid-based speed is a complement to tissue-based testing that for the majority of patients is helpful because we haven’t solved quicker turnaround time as a major obstacle yet. And again, the heterogeneity of referral patterns is unfortunately one that’s not as easily addressable unless you have a biopsy done in-house.

Charu Aggarwal, MD, MPH: Kaushal [Parikh], what are you doing? How’s the Mayo Clinic system handling this, and is your turnaround time fast, or do you think there’s room for improvement?

Kaushal Parikh, MD: There’s always room for improvement. With results for NGS testing and IHCs [immunohistochemistry]. We have a protocol where our pulmonologists take the lead in sending tissue for NGS, our in-house NGS panel, as well as for PD-L1 testing. So more often than not, what’s been happening now is that when I see the patient, I tend to have at least the PD-L1 and the NGS about the next week. In general, the turnaround times have improved from what used to be 3 to 4 weeks to about 2 weeks in certain cases, a little less than 2 weeks as well.

Again, our practice is to get ctDNA, [circulating tumor DNA]; you get liquid biopsy concurrently for all patients. And that also has helped with identification, especially in somebody [for whom] we have a high suspicion for an actionable target, both in the perioperative setting as well as in the metastatic setting. Sensitivity perioperative ctDNA has been challenging, but we’ve had some successes identifying an inappropriate patient to treat in the early stages as well, off-label. With that being said, there is always room for improvement.There are those cases now where we tend to have less tissue, especially with more and more patients getting bronchoscopic biopsies and small specimens.

And the number of tests that we want, often we’ll have patients whose tissue has been sent for the reflex EGFR testing, and then there’s limited tissue left for NGS, and then we have to scrape off slides, which takes a few days. These are still challenges that we are working toward solving.

Charu Aggarwal, MD, MPH: Absolutely. I think this is great the interventionalists are taking the lead. I’m just curious about how it’s occurring at different institutions. Dr [Nagashree] Seetharamu, what’s your practice, and what’s your turnaround time looking like?

Nagashree Seetharamu, MD: As I mentioned earlier, it’s reflex by the pathology department. So as soon as they get the biopsy, from the time of receipt of the specimen in the lab is 2 weeks for tissue-based and liquid, as you mentioned earlier, 7 days. I can count on it being exactly 7 days, and I will get the results. From a pathology standpoint, we discussed how these small specimens are sometimes difficult, but I also find it challenging when the primary is questionable. Sometimes they use up some of the material for immunohistochemistry, trying to identify the site of origin, and you have to put a stop to that process. That’s when we get involved in and triage the specimen for NGS testing rather than doing a whole bunch of immunohistochemistry to identify the site of origin, which is not as important today as it was perhaps several years ago.

Charu Aggarwal, MD, MPH: For sure, and Dr [Tarek] Mekhail, how’s your turnaround time at Advent [AdventHealth Cancer Institute in Orlando, Florida]?

Tarek Mekhail, MD, MSc, FRCSI, FRCSEd: I can second everything that has been said. We have in-house testing with a turnaround time of 7 to 10 days. And I agree with the liquid biopsy comments that the turnaround time is around 5 days. We’ve established the reflex testing. As soon as the pathologist gets an order for one cancer biopsy, testing is already performed. So, for the vast majority of patients I see in my clinic, by the time the patient has an appointment, I have the results. And I think we talk a lot about the turnaround time, but really a lot of the delay is the delay from the time the biopsy is obtained until the test is ordered, or from the time the pathologist sees them, there are a lot more delays that happen before we actually start the testing process.

I always say lung cancer is a team sport; all the parties need to be involved. The pulmonologist or the interventional radiologist is getting the proper tissue, the amount of tissue that’s necessary, the pathologist, so it’s the whole team because any breakdown in getting the biopsy is what will lead to the delay of treatment. And those delays are far more often much longer than actually the 10 vs 7 days that we all always argue and say, “Well, let’s try to make it 7 vs 10. Patients are waiting to see us for 2 weeks or 3 weeks.” Regarding the liquid biopsy testing, I 100% agree with your previous comment. In my practice, I order them concurrently unless I have an actionable result by one.

And an actionable result by one means that I have a positive result. So if I have a tissue that tells me there’s no actionable mutation, that’s not an actionable result. We could have missed it as you published, and [in] other publications, tissue might miss 20%. So in these patients, even if the tissue says there’s nothing, I would do the liquid biopsy. If the tissues give me an informed result, then I perhaps will not order the liquid at the same time or perhaps later on. And if the tissue is not yet the result, then I order the liquid. So the vast majority of my patients would get liquid biopsy.

Charu Aggarwal, MD, MPH: I think you laid out the strategy pretty beautifully. I think if the liquid is giving you an answer, we should just act upon it, but we should not rely on a completely negative liquid biopsy or something that reveals insufficient DNA. Sometimes we see an ND, or “not detectable,” on liquid biopsy that should really be ideally followed with sequential tissue testing or concurrent tissue testing as maybe the treatment paradigm.

Transcript edited for clarity.