Next-Gen Sequencing for Lung Cancer: Do It Early, for All of Your Patients

Mark G. Kris, MD


June 09, 2018

Hello. This is Mark Kris from Memorial Sloan Kettering in New York City, talking, once again, about the benefits of doing next-generation sequencing (NGS) at diagnosis on persons with lung cancer.

We've talked before about the need to get this testing done. In one fell swoop, we can easily get the complete profiling of the genetic abnormalities that can lead us to targeted therapies: point mutations, deletions, insertions, copy number alterations, fusion oncogenes. All of those things can be identified all at once, so you have the information as soon as possible to make the best choices for patients. Please work with your colleagues who obtain biopsies and your colleagues in pathology to get that done.

However, NGS also provides additional information. [In that earlier discussion,] we touched upon tumor mutational burden, a very potent indicator of benefit from immune checkpoint blockade.

Microsatellite instability is another measure for the success of immune checkpoint blockade. Although it's not so rare to find this in other cancers (colorectal cancer being the best example), it is indeed a very rare person with lung cancer who has microsatellite instability. With NGS, you can have this information automatically available, which opens up the door for these patients. If it comes without any additional effort, it's really well worth doing.

There is also the possibility of using NGS to determine the primary site of cancer when you have some question about whether that spot in the lung really represents lung cancer or could be another primary site. Our molecular pathologists now know what common cancers look like in the NGS panels. As a result, they can take a sample that is less well known, that you're not sure about despite the pathologic review and immunohistochemical review, and see how the genetic profile of the tumor in your patient compares to those known tumors.

It's an informatics exercise. It doesn't require additional tissue or additional time. It really doesn't even require additional money, but it can be done as part of NGS.

The other emerging area of NGS is using the same information to prognostically stratify patients. You can use panels of specific genes to identify folks with a better or worse prognosis, and establish algorithms that would define prognosis based on particular NGS results.

This is a bioinformatics exercise included within the NGS. It does not require an additional biopsy. It does require a little time and, of course, needs to be set up by your bioinformatics team. It can be another helpful piece of information that comes from NGS.

The last reminder is that NGS recently has been reviewed by the US Food and Drug Administration (FDA). Although there are still some special issues surrounding NGS testing and getting it paid for, panels have had their diagnostic reproducibility and accuracy determined, by state [department of health] panels for example, which can also be used for FDA approval.[1] The FDA has said that they would accept a number of panels—such as the one from my institution, MSK-IMPACT, and one from a commercial vendor—as an established test for a specific target, practically in lieu of a linked diagnostic test, which frankly is very rarely used.

People talk about the cost, but it is less than one PET scan. Just a small reminder that using PET scans to follow patients with soft tissue disease with an advanced malignancy, at least in lung, is not a standard of care. I know that it is done by many practitioners, including myself, who can do much more expensive tests with no clear-cut guideline recommendation. We can also use NGS testing, which has a lot of guideline-based rationale to use it, particularly for those known targets.

Please get NGS testing done on all of your patients at the time of diagnosis. Work with your colleagues to get sufficient tissue and to get [testing] done quickly, and with your bioinformatics team that analyzes this data and/or your commercial vendors to get the information you need to best care for your patients.


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