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Denise Brock

Molecular Diagnostics Testing and Next Generation Sequencing

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The Global Resource for Advancing Cancer Education (GRACE)
presents 
Molecular Diagnostic Testing and Next Generation Sequencing Webinar Series

Kurt Davies, PhD, Instructor with the University of Colorado Health Sciences Center – Department of Pharmacology, and Nirali Patel MD, Assistant Professor, Department of Pathology and Laboratory Medicine, UNC School of Medicine join GRACE to discuss Molecular Diagnostic Testing and Next Generation Sequencing.  This extremely informative (audio only) webinar series discusses cancer cell biology, targeted therapies, genetic testing, the importance of retesting in cases of resistance, and next generation sequencing.  


 

 

Cancer Cell Biology 101,  Presented by Kurtis Davies, PhD, University of Colorado Anschutz Medical Campus  

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How Targeted Therapies Treat Cancer,  Presented by Kurtis Davies, PhD, University of Colorado Anschutz Medical Campus   

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How it Works: Genetic Testing in Lung Cancer,  Presented by Kurtis Davies, PhD, University of Colorado Anschutz Medical Campus   

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Resistance to Targeted Therapies, and the Importance of Retesting,  Presented by Kurtis Davies, PhD, University of Colorado Anschutz Medical Campus   

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Nirali Patel, MD

 

What is Next Generation Sequencing (NGS)?  Presented by Nirali Patel MD, Assistant Professor, Department of Pathology and Laboratory Medicine, UNC School of Medicine  

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Please feel free to offer comments and raise questions in our Discussion Forums.


GRACE would like to thank the following sponsors for their support of this program

 

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Takeda Oncology

 


Denise Brock

Lung Cancer Video Library – Liquid Biopsies for Broad Next Generation Sequencing Testing

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GRACE Cancer Video Library - Lung

 

 

We welcome Dr. Luis Raez, MD FACP FCCP, Chief of Hematology/Oncology and Medical Director at Memorial Cancer Institute, and Clinical Associate Professor of Medicine at Florida International University with 2017 updates to our Lung Cancer Video Library.  In this recent video for GRACE, Dr. Raez discusses Liquid Biopsies for Broad Next Generation Sequencing Testing.


 

 

 

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TRANSCRIPTS 
Click to download  (coming soon)
 

 Dr. Luis Raez, MD FACP FCCP

Chief of Hematology/Oncology and Medical Director, Memorial Cancer Institute
Clinical Associate Professor of Medicine, Florida International University
 

 

 


  


GRACE Video

Multiplex Testing for Rare Mutations: What Are the Potential Benefits?

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GRACE Cancer Video Library - Lung

GCVL_LU-B09_Multiplex_Testing_Rare_Mutations_Potential_Benefits

 

Dr. Ross Camidge, University of Colorado, discusses the potential benefits as well as the disadvantages of multiplex mutation testing.

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Transcript

More and more, when people are doing molecular testing on their tumor, they’re not just getting one test and if it’s negative doing another test — that’s called sequential testing, they’re doing lots of tests at the same time — that’s called multiplex testing. There are certain good things about that and certain things which are less than good.

In terms of good things, if you do a whole bunch of tests at the same time, you don’t have as long a delay. If you test sequentially it may take you a while before you get to the positive and if you want to make a decision on your treatment as soon as possible, it’s good to get all the information upfront. Also because when you do the sequential testing, each individual way of preparing the tissue wastes some; multiplex testing is a more efficient use of the tissue, so it reduces the chance that you’re going to need another repeat biopsy.

There’s a certain health economic advantage when you utilize multiplex testing, it is what’s called a noncumulative increase in cost. So to look for ten mutations doesn’t cost as much as ten times looking for one mutation. Maybe it costs two or three times as much, and you can add on extra tests.

Perhaps one of the reasons why we’re most enthused by this idea of multiplex testing is you’re going to find some of these rarer abnormalities. Not just the ALK and the EGFR, but increasingly, there’s a collection of abnormalities which are actionable, sometimes through licensed drugs which are not yet licensed in lung cancer but licensed in other diseases, sometimes because they’re an entry into a specific clinical trial. Examples that spring to mind in lung cancer include RET rearrangements, ROS1 rearrangements, and BRAF mutations.

I said there were a few things which were not good. Perhaps the biggest thing is there are some companies commercially doing this who perhaps are adding too many unnecessary tests, and by that I mean tests that really haven’t got any proven value and they’re using up your tissue, they’re increasing the expense to your insurance firm. Perhaps the other downside is that sometimes you get such a wealth of data, like a data dump, you don’t quite know which one to take to the bank. You get all of this information, there are multiple different mutations, and many of them are not driving the cancer, they’re what are sometimes called passenger mutations, and sometimes that ability to sift through it is pushed back onto you or your doctor. Sometimes there’s an algorithm that will print out, “oh, you’re eligible for this trial, or that trial” and there the issue is, what is their metric for saying there’s good enough data to say, “yes, you should go travel to go on this clinical trial.” Sometimes they have a pretty low bar to get over.

For me the best thing to do is — yes, multiplex testing is a good idea, there are certain companies which are better at this than others, and when you get that information you can’t just assume that everything in it is a meaningful result and you really have to sit down, hopefully with an oncologist who understands this, to go through it.


GRACE Video

Blood-Based Mutation Testing: Circulating Tumor Cells and Tumor DNA

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GRACE Cancer Video Library - Lung

GCVL_LU-B10_Ed_Kim_WCLC_2

 

Dr. Ed Kim from the Levine Cancer Institute reviews the potential advantages and current limitations of blood-based testing for molecular markers using circulating tumor cells and circulating tumor DNA in identifying clinically important mutations.

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Transcript

We know there are challenges in trying to obtain biopsies, especially when you’ve already been diagnosed and had treatment, and then the tumor stops responding to the therapy that’s given. We like to do repeat biopsies because we know that the tumor can change over time, after being exposed to different types of therapies. That can sometimes be challenging, and add some risk to patients because it is an invasive procedure — many times we use a needle that will go through the chest, into the tumor, to try and extract enough tissue to make these measurements. Emerging technology that has really been very popular the last few years has been trying to utilize your blood to measure these markers. You’ll hear terminologies like circulating tumor cells, or CTCs, circulating DNA — a lot of different things that are measuring, trying to identify things in your blood that may be representative of your tumor in your chest, or your liver, or where it may be.

One of the technologies is called circulating tumor cells — in this, you are actually trying to isolate these cancer cells in the blood. Some of the technologies are cell search systems, in which you isolate, what we call, through a filter, these tumor cells — that is a bit challenging, it has been inconsistent with some of the results. Also, circulating cell-free DNA is another technology — this, again, is trying to measure small pieces of DNA that are shed from the tumor, and it’s a little easier to pick up that, as opposed to actual, whole cancer cells, in the bloodstream.

There are some commercial tests out there — Guardant360 is one of them, that’s based, again, on the technologies discussed in the NGS section, that would be next-gen sequencing, and also OncoBEAM or Sysmex Inostics — these are also commercial tests, and I can tell you there are many more that are coming. Right now, I would not view them, necessarily, as your first choice, over getting a tumor biopsy. However, a lot of the quality analytics that have been done have shown that they can measure almost as accurately in the bloodstream, using these technologies, as one would taking tumor tissue through a procedure, using an interventional procedure like a bronchoscopy or interventional radiology.

 


GRACE Video

What Is Next-Gen Sequencing?

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GRACE Cancer Video Library - Lung

GCVL_LU-B09_Ed_Kim_WCLC_1

 

Dr. Ed Kim from the Levine Cancer Institute in Charlotte, NC summarizes the mechanism of next generation sequencing (NGS), how it can potentially be used, and its limitations in clinical practice today.

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Transcript

As you know, this is a very, very broad field now — the terminology almost gets mixed into any type of platform testing, or diagnostic testing you’ll hear about, and it’s difficult because it’s not something that’s exclusive, that can be ordered by doctors. This is something that also patients request. There are companies coming from all different directions that can tell you, “this is the test you should order,” or “it could be out of your blood,” “it could be out of your tissue,” and I think it’s important to put it in the context that some of these markers are very useful, but some of them are a little bit more limited. So it’s really good to have a discussion with your physician about what test is appropriate to help determine the best treatment.

Now, if we talk about next-gen sequencing — that’s where the NGS comes from, so any time you hear about NGS, that is what we’re talking about. Now, in the early 2000s and before, what most technologies used was what we call Sanger sequencing, and I really don’t want you to get too tied up into the terminology, but essentially, older technology was like building a railroad — you had to lay down each little piece of the track, one by one, and do it in a sequential manner. You can imagine if you are actually measuring your entire genetic code, that can take a long time — it’s a very exhaustive process, and certainly can miss some things.

With NGS, now, it’s like laying down parallel tracks with railroad producing machines, and so you can lay down multiple tracks at the same time. Now, what you are doing is doing multiple genes in sequence, and in parallel. So, it is a much more efficient method, you’re not missing as many things, and it’s a little less labor intensive — and that’s what has really changed why we can get a lot of genes, or information from your genes, in a quicker, efficient manner, because of this type of platform technology. The other name of it was massively parallel sequencing, but that doesn’t sound as sexy as NGS, so NGS is the terminology that will help you identify what next-gen sequencing and that type of testing is.

There are multiple names of platforms that exist out there, that go under this NGS, or conducting next-gen sequencing: I mentioned Sanger, there’s also Illumina MiSeq, there’s also a Roche 454 sequencing, you also hear terms like ion torrent and ion proton — that also does sequencing, and also solid sequencing. So, just to throw out some names, just in case you hear some of these, just know that they all essentially try to accomplish the same things; some will have more genes, some will have less genes, but what they’re trying to do is identify what abnormalities may exist within the tumor’s DNA, or genes.

As researchers, and scientists, and clinicians, we really like having this type of technology. It really allows us to take a tumor sample from a patient, and study it, measuring thousands and thousands of different genes. However, we know that there are limitations, and we can’t measure all of them — it is very time consuming, and there is cost associated with it. So we try to embed these in the context of clinical research as much as we can, in order to really learn how a tumor behaves, how it reacts to certain therapies, and how it affects the patient overall. It is a useful tool, and you’ll see it and hear about it more and more.


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