Zosia Piotrowska, MD, explains molecular testing methods that can discover molecular alterations in common biomarkers in patients with mNSCLC.
Joel Neal, MD, PhD: There are a lot of genes that we need to test for and a lot of “can't miss” actionable biomarkers. Some of them are mutations and some of them are rearrangements and a little tricker to find. Zosia, way back when I did my medical oncology fellowship training with the legendary John Iafrate, who as far as I can tell invented ALK FISH, invented ROS1 FISH, invented a commonly used RNA testing method looking for some of these unusual rearrangements. I was wondering what's being done standard of care at Mass General these days.
Zosia Piotrowska, MD: So, we are indeed using that assay. Our standard panel includes a DNA, NGS in-house assay as well as an RNA based NGS based assay to which you are alluding. Those are run unfortunately not yet reflexively. Those do require a clinician order. They also in the state of Massachusetts actually require patient consent for genomic testing so there's a couple steps there which I think limit the reflex testing to a certain extent. We do both and that gives us the broadest coverage of these various mutations and rearrangement event. The turnaround time for those assays is about two weeks and actually our molecular pathology group has been really excellent at trying to develop pathways where we have more rapid testing particularly for patients where we think an alteration is more likely. We've had for a while rapid single gene tests looking at EGFR and IHC for ALK and ROS1 and now trying to move even to broader tests being done with a quicker turnaround. This is an evolving field. I think there's a great understanding of the fact that we need to do this testing and we need to do it quickly to be able to make treatment decisions for patients. I anticipate that this area is going to evolve significantly over the coming years or at least maybe I hope that that will be the case.
Joel Neal, MD, PhD: One of the biggest breakthroughs that we've had over the last few years, RNA is a big breakthrough but also liquid biopsy treating. While I made this slide, thank you Dr. Shiller for the shout out because I wanted to show you can find different alterations with different methodologies, but I think overall probably plasma, DNA, NGS sequencing is the fastest and easiest. Tumor DNA sequencing is probably the most reliable for most of the single gene mutation but then for those gene rearrangements I think RNA sequencing is actually easier to find many of them, but RNA is a lay by on molecule that can be very finicky and not always easy to extract from paraffin. I've always said we can always believe a positive test but a negative test from something like liquid biopsy or RNA may pass quality control but still we miss the biomarker of interest, just because it's tough to find. I've also on the left, put a relative percentage of these various gene alterations in a general patient in the US with adenocarcinoma non-small cell lung cancer, regardless of smoking status. General percentages and as Zosia pointed out, KRAS is by far the most common, KRAS G12C now actionable and other KRAS mutations all combined, and EGFR is next most common.