Latest / The Eye Believe Podcast / Eye on the Expert: Eye on ctDNA – What Doctors Are Learning in Uveal Melanoma
Transcript
- 0:03all right everybody
- 0:04um we are kicking off our quarter 2 webinar the Eye On
- 0:08CT DNA and I know it's a little bit of a pun
- 0:10for us to use that all the time but we are so
- 0:13excited to have the guest speakers that we have today
- 0:15um I wanted to start off by thanking you guys our audience
- 0:18everybody who registered and who
- 0:20has started participating um
- 0:23I am so grateful to you guys for you know just
- 0:26playing an active role in your care
- 0:28and in what you learn as patients and caregivers
- 0:30in the uveal melanoma community
- 0:32so um we here at A Cure In Sight are so
- 0:34excited to bring this webinar topic to you about CT
- 0:36DNA and just kind of helping you understand
- 0:38what this test is and how you might um
- 0:41potentially bring it to your doctor
- 0:42as something that you could utilize in your own
- 0:44um medical journey as a uveal melanoma patient so um
- 0:49to kick us off I want to just say huge thanks to our
- 0:51sponsors
- 0:52um we have quite a number of sponsors this time
- 0:55we've got Natera Castle Bio Sciences
- 0:59Aura Bio Sciences Delcath Systems Ideaya Bio
- 1:02Sciences and Immunocore who are all helping to sponsor
- 1:05this webinar
- 1:06um and who are just making this possible so
- 1:08big shout out to them for making this possible
- 1:10and thank you to all of you guys who are registering
- 1:12who are here live and listening
- 1:14um as we get started and I bring on our guests
- 1:16we are going to have a short presentation to start
- 1:19and then we are going to have an opportunity for you guys to ask questions
- 1:22as you have questions
- 1:23you know as Doctor Krainock is presenting um as you hear
- 1:26you know the doctor's discussing
- 1:28please make sure to put those in the Q&A box
- 1:30there should be a section at the bottom where you can
- 1:32click to ask a Q&A or you can uh
- 1:36you can ask in the chat as well I will be monitoring
- 1:38both of those places and we will answer questions
- 1:41throughout and throughout the end of the portion of the webinar
- 1:45um
- 1:45we do have a hard cut off at the hour and a half mark
- 1:47or the hour or
- 1:48yeah hour and 15 minute Mark goodness I gotta
- 1:51calculate time here
- 1:52um but as you guys are popping into the webinar
- 1:54drop in the chat where you're from
- 1:55you guys should be able to chat and just say hi
- 1:58um but with that I'm gonna go ahead and bring our friends
- 2:01and our guests into the webinar
- 2:03thank you guys for joining us um
- 2:04we're gonna actually do a little bit of an introduction
- 2:06round table style so um
- 2:09you guys know who I am I'm Danet Peterson with A Cure
- 2:11In Sight and I'm your host
- 2:12for this webinar and my kind of co host in this
- 2:15in this webinar is Doctor
- 2:17Michael Krainock from Natera so um Doctor Krainock say hi
- 2:21hi everybody
- 2:22I'm Mike Krainock
- 2:24Medical Director at Natera super excited to be here
- 2:26uh Doctor Montazeri you wanna go next yeah hi uh
- 2:30my name is Kam Montazeri I'm a
- 2:32melanoma oncologist at Mass General
- 2:34Brigham Cancer Institute and faculty at Harvard
- 2:38Medical School I have a special focus in uveal melanoma and I'm
- 2:42really happy to be here and thank you for the audience
- 2:45to join
- 2:45Doctor Ma
- 2:46yeah hi uh good afternoon everyone
- 2:49uh my name is Vince Ma
- 2:50I'm a medical oncologist at the university of Wisconsin
- 2:53Carbone Cancer Center uh currently the co
- 2:56faculty lead for melanoma and non melanoma skin cancer
- 3:00um and one of my areas of um
- 3:02special interest and focus
- 3:04particularly in research is also in
- 3:07uveal melanoma so I'm glad to be here today to to
- 3:11to answer some great questions
- 3:13awesome thank you guys so much for being here
- 3:15again for just participating and um
- 3:17with that let's go ahead and get started with Doctor
- 3:19Krainock's presentation
- 3:20and we'll just learn a little bit more about Natera
- 3:22and the signatera test
- 3:24sounds great thanks Danet can everybody see the slides
- 3:27OK they're coming through alright on your end
- 3:29alright wonderful um so once again I'm Mike um I'm a
- 3:34physician scientist and surgeon
- 3:35by background I've been with the company about
- 3:38six years now
- 3:39I do a lot of work in melanoma
- 3:42and other cutaneous oncology as well as
- 3:45thoracic oncology and head and neck oncology um
- 3:49I'm gonna start just by kind of giving you guys a background
- 3:52of the the product
- 3:54portfolio so to speak that that Natera has
- 3:58and then we'll kind of focus in on
- 4:00one piece of what we do which is
- 4:02molecular residual disease testing or MRD
- 4:05and talk about how we do that and why we do that and what we're learning
- 4:10by doing that
- 4:11we'll look at some data in all types of cancer
- 4:14and then we'll kind of focus down from there
- 4:17and look at data across different kinds of melanoma
- 4:21to include some uveal patients
- 4:23um and then I'll pass it off to Doctor
- 4:25Montazeri and Doctor Ma
- 4:27um to kind of talk about specific cases
- 4:30and their specific experiences they've had in in
- 4:33uveal melanoma specifically
- 4:35and then we should have some time for some questions
- 4:38so hopefully by the end you've got a really good sense of kind of what this technology is
- 4:42the state of the field
- 4:44and also the the the clinical data and potential
- 4:47clinical utilities in in melanoma and uveal melanoma
- 4:51so
- 4:53what you're looking at here is kind of a menu of tests
- 4:55that Natera has for cancer diagnostics
- 4:58I'm actually gonna start with the test called Altera
- 5:01so that's a comprehensive genomic profiling test
- 5:04this is what a doctor
- 5:05would get when they want to know if there's specific
- 5:08mutations that are actually driving the cancer forward
- 5:11and the reason that we may want to know that is because there's
- 5:13sometimes there's drugs that we could use specifically
- 5:16for those situations or there's clinical trials
- 5:19that you might be eligible for based off of those situations
- 5:22so that's the Altera test
- 5:24the Empower test is a blood test for hereditary cancers
- 5:27so those are used for
- 5:28or that's used I should say for patients who
- 5:31may be at higher risk because of a family
- 5:33history for example
- 5:34for certain kinds of cancer that run in families um
- 5:37and then our MRD portfolio again molecular
- 5:40residual disease and we'll talk about what that is
- 5:42is kind of comprised of three different tests
- 5:45Signatera Signatera Genome and Latitude
- 5:49Signatera and Signatera Genome uh
- 5:51require tissue and Latitude is just a blood test so we
- 5:55um use different features of of cancers that that are
- 6:00um unique to cancers but we can understand
- 6:02without actually having a piece of the tumor if that makes sense
- 6:05um to track signals uh in the blood
- 6:07we'll talk a little bit about
- 6:09about more what that means
- 6:10um but for the rest of the talk we'll kind of focus
- 6:12on the Signatera and Signatera Genome
- 6:16um so to design a molecular residual disease test um
- 6:19we start with a piece of tissue
- 6:21so what we're gonna do is we're gonna either get a piece of the cancer
- 6:24from a biopsy or a surgical specimen
- 6:27we're gonna take the DNA out of it and we're gonna
- 6:30sequence it we can do that in many different ways
- 6:33um sometimes we do that
- 6:35through what's called an exome sequencing
- 6:37sometimes we do that through what's called a genome
- 6:39sequencing but the
- 6:40important thing to know is that now we have a signature
- 6:43hence signatera of the tumor
- 6:46at the same time we take DNA
- 6:48from a blood sample from the patient
- 6:50and we do a sequencing analysis on that
- 6:53and then we compare those two sequences
- 6:56and the reason we're able to
- 6:58use a tool like this is because there's an
- 7:00important principle here and that is is that
- 7:02cancer genomes
- 7:04look very different than the genome in our non cancer
- 7:08cells so as a lot of the folks in the audience
- 7:10might know cancers um
- 7:14kind of accumulate different kinds of mutations
- 7:16in their DNA and that's what we find
- 7:18we find those mutations that are unique to the cancer
- 7:21that aren't present in your non cancer cells
- 7:24and then we track those specifically
- 7:26and we only need the tissue
- 7:27the one time so when we track those mutations
- 7:29specifically that are unique to the tumor itself
- 7:32we can do that just through a blood draw so tissue
- 7:35once and every time we look for these signatures
- 7:38it's just a blood draw if you have any questions
- 7:40about that you can drop them in the chat
- 7:42we should have some time at the end to go through that more
- 7:44but that's kind of the general
- 7:45principles of how we set up this test we're looking for
- 7:48mutations
- 7:49in the blood that we know are coming from the tumor
- 7:53we've been at this for a long time now actually
- 7:55um so this test has been available since 2,019 it's
- 7:59it was in development for years and years before that
- 8:02lots of very smart people working on this at
- 8:04institutions all over the world
- 8:06um we now have over actually 145 publications
- 8:09out there around this technology we're actually
- 8:12responsible for over 90% of all the literature
- 8:15uh in this space as it pertains to tissue informed
- 8:18commercially available assays all that work has now
- 8:22resulted in data that's reported out across
- 8:2430,000 patients and 30 different tumor types
- 8:27over half of US oncologists have ordered this test
- 8:30and that represents testing across
- 8:32over 300,000 patients as part of clinical practice
- 8:35so the test is available
- 8:37we have a very good team that helps support testing
- 8:40in the clinic to make sure that the tissue
- 8:42is acquired and the
- 8:43results are returned and if there's any questions
- 8:45about interpretation
- 8:47physicians and patients have a lot of support
- 8:50you're probably thinking about payment
- 8:52um we do have Medicare coverages
- 8:54rolling in as you may or may not know you typically
- 8:56have to apply for uh Medicare coverage by indication
- 9:00so you can't kind of do it once you have to do it over and over and over
- 9:03again
- 9:04at least in the case of these types of diagnostics
- 9:07so that's a long process but we um
- 9:09commit a lot of time and energy to that so that we could get
- 9:12different indications
- 9:13approved for reimbursement by Medicare
- 9:15it's a very similar process for private
- 9:17insurance as well private insurance will typically
- 9:19follow Medicare's lead um so over time
- 9:23more and more of these approvals come through
- 9:25you could see the ones that we have already
- 9:28we have a bunch more we're working on every day now
- 9:31but I do like to note that we actually don't balance
- 9:33bill patients so as of you know now
- 9:36there's no financial toxicity to testing
- 9:38so you shouldn't get a bill even if you um
- 9:40aren't covered by Medicare
- 9:42if you have private insurance
- 9:43and they decline to cover
- 9:44we don't send the balance
- 9:45to you that's how it is today
- 9:48um
- 9:50all right so how do we interpret the results
- 9:52um so what you're seeing here are called
- 9:54Kaplan-Meier curves uh KMs
- 9:56for short you may have heard of these or seen these
- 9:59um and you're looking at two populations of patients
- 10:01that are separated based off of if our test
- 10:04is positive or if our test is negative
- 10:06you could see those two lines
- 10:07do not look alike right they're different colors
- 10:09they're also very far apart
- 10:11and so what we're looking here
- 10:12is that the probability of being free of relapse
- 10:16relapse free survival
- 10:17over time based off of a result with our test
- 10:22so you could see if you're CT DNA negative
- 10:24that's MRD CT DNA negative our test is negative
- 10:28you're on that green line
- 10:29right you have a higher probability
- 10:31of being free of disease
- 10:33compared to if you're on the blue line
- 10:35which is if you're CT DNA positive
- 10:37so a lot of you may be familiar with biomarkers
- 10:39what we call prognostic biomarkers
- 10:42this is very powerful prognostic biomarker
- 10:45right we could tell um
- 10:47very early and and very accurately through this test
- 10:50uh if patients positive
- 10:53they have a very high risk of having persistent disease
- 10:55that will eventually be able to see on a scan
- 10:58versus negative they're much less likely to do so
- 11:01doesn't mean they never will no test is perfect ours
- 11:03included um however
- 11:05you have you could see the the likelihoods here uh
- 11:08across different tumor types of being free of disease
- 11:10or not free of disease over time
- 11:13can you make treatment decisions
- 11:14around that that's the big question
- 11:16prognostic information is great can we do anything
- 11:19about it um it's a much harder question it takes
- 11:22a lot of patience
- 11:23and a lot of time to answer that question
- 11:25and that's what we're actively
- 11:26working on now that's pretty much what my job boils
- 11:28down to is finding out can we do that
- 11:31so I'm showing you data across a few different
- 11:34studies here in a few different cancer types
- 11:36we'll start across the top with colorectal cancer
- 11:39um so we published this in a really big journal called
- 11:41Nature Medicine in 2024 and what you're seeing
- 11:44here again there's those km curves
- 11:46you're seeing that if you're positive by our test
- 11:49after surgery
- 11:50it was better to get chemotherapy right the blue line
- 11:54has a better freedom of disease
- 11:57result than the red line
- 11:58so if you're positive you wanted to get
- 12:01chemotherapy after surgery it improved your outcome
- 12:04in terms of your freedom from recurrence
- 12:07if you were negative you'll notice those lines
- 12:09don't look like the lines in the positive
- 12:11group right they're right on top of each other
- 12:14what that means is there was no difference
- 12:16so if you were negative by CT DNA
- 12:18and you got adjuvant chemotherapy it actually
- 12:21didn't change your outcome in terms of your disease
- 12:23free survival so very exciting right this suggests
- 12:25you could potentially use a molecular test
- 12:28to make decisions about chemotherapy after surgery
- 12:31in colorectal cancer as you can imagine
- 12:33this is the type of thing we have to do over and over and over
- 12:36again
- 12:37before it becomes the norm but certainly very exciting
- 12:40data here and and we hope what the future looks like
- 12:43similar data in the blue box
- 12:45there that's now looking at adding
- 12:47another drug to the usual regimen of chemotherapy
- 12:49called celecoxib you guys may have heard of that
- 12:53you could see
- 12:53again we have two different sets of lines
- 12:56the lines on the bottom are far apart from one another
- 12:58those are the patients who are positive after surgery
- 13:01the lines at the top are right on top of each other
- 13:03telling you there's no difference between those patients
- 13:05with um the drug or a placebo
- 13:08and those are the negative patients
- 13:10so again selecting patients by
- 13:12CT DNA to to predict who will benefit uh
- 13:15from an intervention in this case
- 13:17the addition of celecoxib the standard
- 13:19adjuvant chemotherapy adjuvant meaning after surgery
- 13:22and then again looking at the bottom um uh
- 13:25charts here now we're looking at um
- 13:27urothelial carcinoma
- 13:29kind of commonly collectively called
- 13:31muscle invasive bladder cancer very similar idea
- 13:34the curves at the bottom are the positive patients
- 13:37the curves
- 13:38at the top that are kind of shaded out are negative
- 13:40patients you can see the negative patients
- 13:42those curves are right on top of each other
- 13:44telling you there's no difference between
- 13:46um getting a drug or not getting a drug
- 13:48the curves on the bottom are the positive patients
- 13:50and you see those are separated right you can clearly
- 13:53see at the bottom those curves do not
- 13:55sit on top of each other
- 13:56meaning there's a difference there
- 13:58in this case that difference was
- 13:59significant from a statistical perspective
- 14:02and that means that we were able to give patients
- 14:04a repossitive drug
- 14:05in this case Atezolizumab and again improve their
- 14:08outcome
- 14:09in this time we're showing both freedom from disease
- 14:11and overall survival
- 14:12meaning you were more likely to just be alive in general
- 14:15if you were positive and got the drug versus positive
- 14:18and didn't get the drug
- 14:20um
- 14:21last slide on the same point um
- 14:23we kind of confirm this um actually in the last year
- 14:28um and published this result in a big journal
- 14:31you've probably heard of the New England Journal of medicine
- 14:33uh showing that you could prospectively
- 14:35meaning ahead of time pick patients
- 14:37who stood to benefit from in this case
- 14:39Atezolizumab after surgery for bladder cancer
- 14:43and this resulted just this week in a positive FDA
- 14:46approval for
- 14:47this test as what they call a companion diagnostic
- 14:50for muscle invasive bladder cancer so that means now
- 14:53you could use this test officially to select who
- 14:56stands the benefit from this drug Atezolizumab
- 14:59after they've had surgery for their bladder cancer
- 15:01so very exciting
- 15:02and I hope this gives you kind of an idea um
- 15:05of of where the company's
- 15:06headed and the kind of things that we're working on
- 15:09moving into melanoma um this is all comers
- 15:12all different kinds of melanoma we recently
- 15:14published this um
- 15:15again we're we're looking at those km curves
- 15:17you can see we're looking at um
- 15:19recurrence free survival
- 15:21again the proportion of patients
- 15:23um who are likely to be free of disease over time
- 15:25based off of being CTNA negative or positive
- 15:29this is looking at
- 15:31melanoma patients after resection stages 1 through 3 b
- 15:35so again you want to see that wide separation
- 15:37of those two different groups and we see that here
- 15:40very powerful biomarker
- 15:41what this tells you is that if you've had surgery for melanoma
- 15:45and you're found to be positive by Signatera
- 15:48and nothing is done
- 15:49you're much more likely to have a recurrence
- 15:51that's what this data suggests
- 15:53right in front of us here and so can we leverage
- 15:56that to help us think about surveillance
- 15:59and treatment decisions in a more personalized
- 16:01way that's the kind of the question
- 16:04um one thing you'll see over and over again is that
- 16:07you know and doctors Montazeri and Doctor
- 16:09Ma will tell you
- 16:10as doctors we use a lot of different things to
- 16:14think about your risk of recurrence
- 16:17classically we look at the path report
- 16:19and the features of the tumor
- 16:21to make these risk decisions and we we base
- 16:24our recommendations for
- 16:25therapy after surgery or after radiation
- 16:29in many ways on
- 16:30the the nature of the tumor and all these special
- 16:33features of the tumor that we're interested in
- 16:35what we're finding out is that your status
- 16:37with our test is the most powerful predictor
- 16:40when you compare them to the things we classically use
- 16:43so you could imagine this list could be a lot longer
- 16:46right we could have we think about a lot of stuff
- 16:48but in this particular case
- 16:50compared to these other things that we looked at
- 16:53CT DNA was the most powerful predictor of outcome
- 16:58compared to your stage sex and mitotic rate
- 17:02um this is actually some data from Doctor Ma
- 17:05um this is melanoma data which now includes
- 17:08a subset of patients with uveal melanoma specifically
- 17:11um and what we're looking here is the change
- 17:13in the value of the circulating tumor DNA MRD test
- 17:17and how that correlates with what we call disease
- 17:20control and objective response so you see three
- 17:24colors at the bottom progressive disease
- 17:28disease control and objective response
- 17:31as you could probably guess progressive disease is
- 17:35is the least favorable of those things
- 17:37and what we're seeing here is that the
- 17:39the change in the amount of CT DNA in the blood
- 17:42can help us predict which bucket you're gonna fall in
- 17:46right
- 17:46so you could see the median change in quantitative
- 17:49value by those three categories
- 17:51so patients with disease control had a median
- 17:53decrease of 82% in their quantitative value of CT
- 17:56DNA in the face of therapy
- 17:5888.3% for objective response
- 18:02and then the complete opposite right a rise
- 18:06in progressive patients so if the CT DNA is going up
- 18:10this would suggest you have a much
- 18:11greater chance of having disease progression
- 18:14can we use that information
- 18:15does it add any advantage to your care
- 18:18can we tell that you're gonna progress
- 18:20before you progress and importantly
- 18:22can we leverage that information to prevent
- 18:24that or delay that
- 18:26can we improve your outcome using this information
- 18:28that's the job in front of us
- 18:30so CT DNA decreasers had 30 times higher odds of disease
- 18:33control
- 18:35and 23 times higher odds of objective response
- 18:38um very similar data
- 18:40presented in a different way there's those good old kms
- 18:42again um
- 18:43now we're looking at progression
- 18:45free survival and overall survival
- 18:47we're asking about um
- 18:48the change in the quantitative value of CT
- 18:50DNA after one cycle of
- 18:52a class of drugs called immune checkpoint inhibitors
- 18:55you've probably
- 18:56heard of these and are familiar with these
- 18:58we're looking at patients who went down
- 19:00after a dose versus patients that went up
- 19:03and again you see separation in the curves
- 19:05here for progression free survival
- 19:07and overall survival
- 19:09and then importantly
- 19:11one step further we asked about clearing your CT DNA
- 19:15and what you really wanna see is that you start
- 19:17from some quantitative value you start on a treatment
- 19:21you go down right away and then shortly thereafter
- 19:24it goes
- 19:25away we can't see it at all in the blood anymore
- 19:27and that's what you're seeing
- 19:28here so you have three groups of patients
- 19:31green patients had clearance of CT DNA on therapy
- 19:34blue patients had a decrease
- 19:36but didn't make it to clear
- 19:38and then orange patients had a rise
- 19:40better to be towards the top of the graph
- 19:42than the bottom it means your probability of being
- 19:45alive and free of disease is better the higher you are
- 19:48and you can see we have wide separation
- 19:50of the clearance curve
- 19:52from those patients who didn't clear CT DNA
- 19:55so you can imagine we have now
- 19:57potentially a real time biomarker to adjudicate
- 20:00response prediction
- 20:02based off of kinetic change very early on therapy
- 20:06right so we hope the future
- 20:07looks like we don't have to sit
- 20:08around and wait for scans
- 20:10to show us what's going on we could very very early
- 20:13through a blood test
- 20:14understand if the current medications
- 20:16that you've been prescribed
- 20:18are gonna get you on the green curve
- 20:20right if not can we do anything
- 20:21about that can we change things can we intensify things
- 20:25um all all in the name of improving the outcome
- 20:29so I know that's a lot of information
- 20:30I tried not to be too crazy technical with it
- 20:33uh if you have questions please we can go deeper
- 20:36um but at this point I will hand it off
- 20:38to doctors Montazeri and Ma um
- 20:41to talk about their experience with the testing
- 20:43awesome thank you so
- 20:45okay who wants to go first
- 20:48I think Doctor Ma has some cool slides okay Doctor
- 20:52Ma we're gonna put you on the spot
- 20:53easier to follow than Doctor Krainock very
- 20:56academic talk no it was great very fascinating
- 21:01yeah no I appreciate Doctor Krainock
- 21:05yeah going through a really wonderful overview
- 21:07of CT DNA and some of the amazing data
- 21:09you know that we obviously see in
- 21:12you know both melanoma but other
- 21:13cancer types so as you all know it's
- 21:15such an evolving field right um
- 21:18and so you know I do have a a few slides
- 21:21I'd be happy to sort of share with the audience
- 21:23just to kind of give you all a little bit of like a real world
- 21:25perspective of like how
- 21:27me as a medical oncologist is sort of using this test
- 21:29in in real practice
- 21:32and and certainly
- 21:32the two examples I'll I'll share are patients
- 21:35with uveal melanoma
- 21:38so I'll go ahead and share my screen
- 21:40and hopefully you all can see my screen okay
- 21:44yeah you're good you're full screen excellent thank you
- 21:48so um you know just to share a couple of examples
- 21:50this first case
- 21:51is actually a gentleman that I cared for um in his 70s
- 21:55who was diagnosed with a right
- 21:56eye choroidal melanoma that was class 2 and prame
- 21:59positive
- 22:00and was treated with brachytherapy back in 2020
- 22:04and so unfortunately
- 22:05you know during surveillance because um
- 22:08he was considered to be high risk
- 22:10he actually ended up developing
- 22:11new liver metastases in January 2,024
- 22:15um you know he was um HLA tested and was negative but
- 22:19after sort of reviewing a variety of different options
- 22:22available um he actually ended up um opting
- 22:25for treatment
- 22:26with melphalan percutaneous hepatic perfusion therapy
- 22:30um and as some of you in the audience
- 22:31may know it's also known as Hepzato
- 22:33as the commercial name so you know um
- 22:37what was really phenomenal
- 22:38about his treatment was he actually did very well
- 22:41with therapy you know this uh screen
- 22:44here to the left is actually an image of his belly
- 22:47and what you can see there
- 22:49with that particularly yellow
- 22:50arrow it's actually pointing to a pretty large
- 22:53liver tumor that's his melanoma liver metastasis
- 22:57it measured about 7 to 8 centimeters in size
- 23:01and after about one treatment of melphalan
- 23:04PHP or Hepzato um you can kind of see that the tumor
- 23:07shrunk by almost about 50%
- 23:09and so as you can kind of imagine um in my practice
- 23:13what I have typically
- 23:14been doing and this is something I actually
- 23:16offer to my patients is
- 23:18you know would you like to be monitored
- 23:20with circulating tumor DNA
- 23:22not necessarily by itself
- 23:24but as sort of a a compliment
- 23:26as a way to kind of see how well
- 23:29you're benefiting from treatment um and so the patient
- 23:32actually opted to to participate in it and and as
- 23:35Doctor Krainock has sort of mentioned
- 23:37what we did was we submitted um
- 23:39one of his liver tumor biopsies
- 23:41to actually build the personalized assay
- 23:44and we were actually able to assess a baseline
- 23:47circulating tumor DNA before he was started with
- 23:50um Hepzato so you can see here this little
- 23:53a top blue dot here to the far left and we serially
- 23:57meaning we checked his CT
- 23:59DNA level throughout the course of treatment
- 24:01and you can see here just like what we saw on his CT
- 24:04scan his CT DNA level actually downtrended quite
- 24:08beautifully well so you know a very nice complimentary
- 24:12test to kind of how he is doing
- 24:14with treatment and a good way to monitor his progress
- 24:18now of course you know during the course of therapy
- 24:21you know as he was getting um
- 24:23additional cycles of melphalan PHP
- 24:27you know we noticed that he's obviously
- 24:29continuing to do great
- 24:30I mean you can look here in the far right
- 24:33CT scan image here his tumor
- 24:36shrunk quite nicely and this was after three cycles
- 24:39of melphalan a PHP and so the tumor
- 24:43continues to shrink so he's obviously doing
- 24:46phenomenally well but what was really interesting
- 24:49especially in this particular case example was using
- 24:52circulating tumor DNA as a monitoring tool
- 24:55you'll sort of notice in particular
- 24:57that as we're monitoring the amount of circulating
- 24:59tumor DNA the levels were starting to rise
- 25:02you know with subsequent cycles of treatment
- 25:05and I'm like well why is that the case right
- 25:09especially if the tumor is
- 25:11continuing to shrink in the liver and
- 25:13mind you and as a reminder
- 25:15uh his disease was really just confined to the liver
- 25:18so
- 25:19you know how did I sort of use this sort of information
- 25:22right as a medical oncologist
- 25:23who is certainly wondering why is the CT
- 25:26DNA level rising you know where in particular
- 25:29could the CT DNA level be coming from
- 25:32particularly if his tumor is
- 25:34continuing to do incredibly well in terms of shrinkage
- 25:37from the therapy and so what this ultimately
- 25:40led to was it prompted
- 25:41me to actually do some additional imaging
- 25:44so it actually
- 25:45prompted me to sort of adjust a different modality
- 25:48in terms of how I can assess what's going on
- 25:51and so what I ended up doing was getting a pet CT scan
- 25:54and what I had discovered
- 25:55was that he was actually found to have new bone
- 25:58metastasis and so that would not otherwise
- 26:01have been picked up that well
- 26:02with some of the standard imaging
- 26:04that I was using for him such as the MRI and CT
- 26:07and so you can kind of see here
- 26:09using CT DNA can actually be a very powerful tool
- 26:13to not only help with monitoring treatment
- 26:15response but it actually can help me as a provider
- 26:18really prompts me to do um earlier assessments
- 26:22with scans particularly if a CT DNA level
- 26:25is rising during the midst of therapy
- 26:28and in this particular case example
- 26:29change in an image modality especially
- 26:32if the standard of what I'm using is not sufficient
- 26:35enough to capture
- 26:36what's going on with the disease status in the body
- 26:40so that was just one
- 26:42interesting case example another one is a case
- 26:46of a patient who I also cared for she's in her 70s
- 26:49and was diagnosed with a right eye choroidal melanoma
- 26:53she had a class 1 prame
- 26:54positive tumor and was treated with enucleation
- 26:57back in 2016
- 26:59um she actually unfortunately
- 27:01six years later developed
- 27:03long liver and pancreas metastases
- 27:07um she was HLA-02:01 positive but um
- 27:11around the time when she developed metastatic disease
- 27:14a really main feasible options were
- 27:16immune checkpoint inhibitors as Doctor Krainock
- 27:18mentioned it's a type of a immunotherapy treatment
- 27:22so she was treated with
- 27:24ipilimumab and nivolumab but unfortunately um her tumor
- 27:28actually progressed on this particular therapy
- 27:31and unfortunately around the time that she progressed
- 27:34we now had the availability
- 27:35of Tebentafusp also known as
- 27:38uh Kimmtrak is the commercial name
- 27:40um as an available option for her
- 27:43and so what we actually ended up doing
- 27:44for her was we actually did a combined approach
- 27:47therapy so we did both radiation therapy as well as
- 27:51Tebentafusp as her treatment so
- 27:55what was really great about her particular case
- 27:58was you know when we did the radiation therapy
- 28:01um as well as the Tebentafusp we actually checked
- 28:04the level after she had sort of started both therapies
- 28:07we actually did not get a baseline but
- 28:10what's pretty awesome about this particular
- 28:12case was that she actually had an undetectable
- 28:15circulating tumor DNA so
- 28:17in some ways it gave me a level of confidence
- 28:20knowing that you know she probably or most likely had
- 28:23a very low burden of disease or maybe
- 28:26we might be sort of getting to a point where you know she has
- 28:28more so just microscopic disease
- 28:30that we just can't detect
- 28:31by circulating tumor DNA testing now of course
- 28:36how have I been monitoring her on treatment well
- 28:39I've been getting pet scans
- 28:40on her so what I've been doing is getting a pet
- 28:43scan on her every two months
- 28:45while she was on Tebentafusp and what's very
- 28:48interesting as you can see here is that the arrow
- 28:51is actually pointing to an area that's very hot um
- 28:55suspected to be an area that um
- 28:57her melanoma had spread to in this case her pancreas
- 29:02now you might be sort of wondering
- 29:04whoa why is it lighting up right well
- 29:08we know that her melanoma had spread to the pancreas
- 29:11but because we had delivered radiation
- 29:13therapy to that site
- 29:15it's very probable that this ongoing inflammation
- 29:18may actually be
- 29:20um just the residual inflammation from her
- 29:23radiation therapy
- 29:24and not necessarily from active cancer and so
- 29:29the CT DNA blood testing sort of give us
- 29:32gives us sort of that level of sort of reassurance
- 29:35for her and as you can see here as I
- 29:38continue to get pet CT scans we still see that her CT
- 29:42DNA levels that accompany the scans continue to remain
- 29:46undetectable so to some extent
- 29:48it gives me as well as the patients a relatively
- 29:51high level of confidence
- 29:52that the disease remains under control
- 29:54while I continue Tebentafusp now after the patient
- 29:59has been sort of on treatment for almost two and a half years
- 30:03um what sort of happened was we unfortunately
- 30:05started to detect
- 30:07circulating tumor DNA positivity in her blood
- 30:10and of course we got a pet scan sort of
- 30:13around that time and
- 30:14again two and a half years of therapy
- 30:17and interestingly enough I cannot
- 30:20find any sort of new signals
- 30:22or any new abnormalities anywhere and again
- 30:26this arrow points to that area of inflammation
- 30:28around her pancreas
- 30:30and so what did this sort of information
- 30:33help me with particularly with a positive
- 30:35CT DNA test was well I gotta go searching
- 30:38for where the heck this is coming
- 30:40from so that I could potentially think about
- 30:42intervening with a new level or new line of therapy
- 30:46and so what I ended up doing
- 30:47was we did some additional testing and had found
- 30:51that she was found to have a cardiac or heart
- 30:54metastases that would not otherwise be easily detected
- 30:58by a pet scan generally speaking pet scans
- 31:01tend to light up pretty well on the heart
- 31:03because it's a very metabolically active organ and so
- 31:07really how what did I use the CT
- 31:09DNA testing in this particular case was
- 31:12it really prompted me
- 31:13again to also think about a different imaging modality
- 31:16and it gave me a good idea of what may be sort of a
- 31:20potentially false positive or abnormal
- 31:23uptake in a pet scan that would otherwise
- 31:26look like cancer
- 31:26but is unlikely the case because the DNA's levels
- 31:29negative it allowed me to get confidence about okay
- 31:33if it becomes
- 31:34positive that's where we need to think about
- 31:36is there other disease elsewhere and of course
- 31:39you know with this positive information
- 31:41here it sort of aided me in the assessment of
- 31:44how the patient was doing with her
- 31:46current line of therapy specifically with Tebentafusp
- 31:48so really
- 31:50long story short is you know I've been using
- 31:52CT DNA as a tool to complement imaging
- 31:55but also using it in a way to help me identify ways to
- 31:59change imaging
- 32:00but also think about next lines of therapy so
- 32:05hopefully that kind of gives um
- 32:06a little bit of a perspective
- 32:07of you know how I've been using this test
- 32:09but um but yeah I would love to see and hear
- 32:12um how Doctor Kam
- 32:14Montazeri has been using this test in her practice
- 32:17as well fascinating slides
- 32:19thank you so much thanks to both of you yeah similarly
- 32:22um this has been very helpful in
- 32:25some of the challenging
- 32:26cases especially as you mentioned with
- 32:28Tebentafusp because um
- 32:31as uh many people may be aware it has a very
- 32:35low chance of showing radiographic response
- 32:38and most of the patients
- 32:39that actually do benefit from that they have um
- 32:43the lesions
- 32:43look bigger on the next scan that the patients have
- 32:46initially um
- 32:48it was a little hard to you know convince yourself
- 32:52as a specialist and also convince others to
- 32:54continue the treatment
- 32:55while you see lesions getting bigger
- 32:57and now this does not apply to everyone
- 33:00on the treatment but um there was also a similar um
- 33:05a test similarly to what Doctor
- 33:07Ma showed you guys um the um
- 33:10um basically investigators um had collected
- 33:14blood samples from the patients
- 33:15that were treated from the uh
- 33:17face on the phase 3 study of Tebentafusp
- 33:20and they looked at um
- 33:22the CT DNA levels of these patients and um
- 33:26interestingly those patients
- 33:28that had negative CT DNA or they had
- 33:31uh cleared out um their CT DNA's um
- 33:34early on during the treatment they did better
- 33:37and those patients that had um
- 33:40basically
- 33:40reduction any type of reduction in their CT DNA levels
- 33:44they actually
- 33:44continue to benefit from Tebentafusp despite um
- 33:48radiographic disease progression
- 33:50so in some ways it is a very helpful tool if um
- 33:54you don't have um
- 33:55a better way of um assessing response to disease uh
- 34:00during the treatment
- 34:01it has actually happened to me as well that um
- 34:04because of as per the guidelines and also per um
- 34:09the natural history of uveal
- 34:11melanoma we worry more about the liver and um
- 34:14for active surveillance of the patients
- 34:16most of us use some sort of liver imaging
- 34:19usually an MRI of the liver which is very precise and
- 34:24sometimes
- 34:25depending on how much you're worried that somebody
- 34:27may have disease recurrence you also use CT
- 34:30of CT scan of the chest to also monitor the rest of
- 34:34and the rest half of the body
- 34:35but sometimes you can't see
- 34:37some subtle changes in the bone or somewhere else
- 34:40and um I had a similar case that um
- 34:43actually one of the participants asked how we can um
- 34:48develop this CT DNA assay if the patient had um
- 34:51hasn't had any biopsy or disease progression
- 34:54if somebody has had um
- 34:56enucleation in the past you can use that tumor um
- 34:59as basically an
- 35:02a tissue to make in the assay
- 35:05or the tissue template
- 35:07so that's what we had done for that patient of mine
- 35:11and yes we saw a significant rise in CT DNA
- 35:15and our detective work began and with
- 35:19the pet scan we found a lot of very small diffused
- 35:23lesions on the bones and um the
- 35:28then we started the treatment which probably would have
- 35:33not been as successful if we had started
- 35:35the treatment later
- 35:36sometimes unfortunately we don't have these tools
- 35:38because if you have a fine needle
- 35:40aspiration biopsy from your
- 35:43primary lesion
- 35:44unfortunately that's too small at least with the
- 35:47technology these days to make a template um
- 35:51so there is no
- 35:52close to perfect assay in that setting yet
- 35:57however this is a helpful tool the other way
- 36:00that we have used it is that sometimes
- 36:03when a patient has had disease progression
- 36:07on a certain treatment
- 36:10based on you know where the
- 36:12growing lesion is and how many growing lesions are
- 36:15instead of taking
- 36:18instead of changing the whole systemic therapy we
- 36:22decide to add some local therapy
- 36:24either radiation therapy or
- 36:26liver directed therapy or cryoablation depending on
- 36:30where and how many lesions we have and um
- 36:34there was also some evidence of um
- 36:37additional benefit to um
- 36:39continuing the systemic therapy in a disease
- 36:42that has very few effective treatment
- 36:44options and adding some treatment and you can
- 36:46see actually that CT DNA pattern uh
- 36:49dropping and giving reassurance to both
- 36:52us as clinicians and also the patient
- 36:55awesome thank you guys both so much and Doctor
- 36:57Krainock thank you so much for your presentation as well
- 37:00um we are getting inundated with questions
- 37:01from the audience so this is great
- 37:03but I'm gonna run through the chat first because we
- 37:06started to address this and I wanted to just make sure we clearly
- 37:08answer um can this test like the Signatera test um
- 37:12a tumor informed
- 37:13CT DNA be done from the primary eye tumor
- 37:16or just from metastases
- 37:18what are you guys seeing and I know Doctor Montazeri
- 37:20you kind of touched on this a little bit
- 37:22yeah it depends on how much and then Doctor Krainock is
- 37:24the best person we have
- 37:26actually the actual person that we depend on
- 37:29to make the um test but um
- 37:32it depends on how much tissue we have
- 37:34um with just a small needle
- 37:36biopsy there's not gonna be enough tissue to make that
- 37:39um
- 37:40if you had a surgery to remove um
- 37:44the actual tumor meaning enucleation or
- 37:47from the metastatic tissue
- 37:49most of the time it's possible to make that assay
- 37:52yeah uveals I mean as everybody in this crowd knows
- 37:55tough because there's not a lot of tissue to go around
- 37:57um we're always making progress
- 38:00on the input material needed to design so you know
- 38:04every year it seems like we can do it with less and less
- 38:08um in other cancers you know
- 38:11we have designed successfully
- 38:12from fine needle aspirates
- 38:15even of metastatic lymph nodes where you know
- 38:18you may not have a ton of cancer cells there um
- 38:21so we are like I said tumor informed
- 38:23for Signatera so we do need some
- 38:25we will try with very little and we will have
- 38:28success but as Doctor Montazeri has alluded to
- 38:32the more we get
- 38:34to design from the better the chances we could design
- 38:37um
- 38:38we do have that latitude test that is tumor naive
- 38:42meaning we don't need any tumor tissue at all
- 38:44um so that may be something that is uh valuable for uh
- 38:49you guys uh providers and patients in the next uh
- 38:53you know couple of years as we roll out our tissue
- 38:55naive test
- 38:57um so I would say
- 38:58we we will try from pretty much anything
- 39:01um and and we are good at small input volumes
- 39:06um and getting better
- 39:07and but we do fail to design sometimes
- 39:11and uveal's one of those words especially tricky
- 39:13because there's not a lot of tissue to go
- 39:14around that's absolutely true yeah for sure
- 39:17um this look
- 39:18this question is also kind of pertaining to the
- 39:21obtaining a sample using a sample
- 39:23this person is asking if if you had a Caris test done
- 39:26um
- 39:27so like that's typically
- 39:29the liver biopsy I think for those of you guys listening who don't know
- 39:32um
- 39:32if you have the Caris test done can they use the Caris
- 39:35existing test
- 39:36for the initial sequencing of the Signatera
- 39:39it's a great question super insightful question uh
- 39:41unfortunately no haha um so
- 39:44so we have to do it it's a great it's a great
- 39:48idea right cause there's not a lot of tissue to go around
- 39:50um
- 39:52but the way these labs all all labs are are um
- 39:57set up and regulated
- 39:58right it's very specific you have to follow very specific
- 40:01standard operating procedures
- 40:03to stay within compliance of regulatory bodies and
- 40:07uh quality assurance metrics
- 40:09and so the short answer is we we cannot mix sequencing
- 40:14amongst companies even amongst academic collaborators
- 40:20without going through super super specific and strict
- 40:23protocol developments um so unfortunately
- 40:26whoever asked that question
- 40:28that's a super insightful question um
- 40:31and you really understand the concepts
- 40:33here but unfortunately no we can't do that
- 40:37maybe to also follow up on that as well
- 40:40you know because to to develop a Signatera
- 40:43personalized assay you have to have you know
- 40:46sufficient tissue to build that assay and so you know
- 40:50I really find that biopsies
- 40:52or tumor tissue is just so incredibly valuable
- 40:54right cause we can use that information to do
- 40:57sequencing in the tumor look for mutations
- 41:00that might inform treatment options down the road
- 41:02and in this case we can also use it to develop a CT
- 41:05DNA assay and so what I often encourage patients
- 41:09and even other providers
- 41:10to think about is that before you send off that tumor tissue
- 41:13for testing
- 41:15for whatever reason you know make sure that it
- 41:17is there
- 41:17enough of it that could potentially be utilized for
- 41:20other testing as well
- 41:22because I've had and I've run into situations where
- 41:25if you submit it for NGS testing there is just not
- 41:29enough sufficient tissue to unfortunately do
- 41:31Signatera testing for the patient
- 41:34one way Natera
- 41:34is trying to get around this
- 41:36not get around this but tried to um solve this is by
- 41:41learning how to do the Altera
- 41:43that I showed and the Signatera
- 41:44test from the same tissue
- 41:46right so we're able to do that with Exome base
- 41:49Signatera and Altera
- 41:50today and I hope within the year
- 41:52we're able to do that with um Signatera genome
- 41:55and Altera so then
- 41:58you could do what the audience
- 41:59participant is suggesting
- 42:00right you could take one piece of tissue
- 42:02you could get a comprehensive genomic profiling assay
- 42:06completed and those results back
- 42:07and then as a completely separate test
- 42:09from the same piece of tissue
- 42:11you could get your Signatera assay
- 42:14so within the same company
- 42:16or the same
- 42:17academic center would have you it's a lot easier to do that type of stuff
- 42:21yeah that makes sense and I think you know just from
- 42:23from a perspective like thinking about the different
- 42:25biopsies and things that we have going on as patients
- 42:28most patients
- 42:29at the primary tumor stage like with the eye tumor
- 42:31are mostly having the Castle Biosciences test um
- 42:35which has been proven
- 42:36you know to be a really good genomic sequencing
- 42:38but it would be really really
- 42:39interesting to see if over time we could you know
- 42:42start using those needle point uh biopsy
- 42:44and if they could just take two samples
- 42:45at the needle point biopsy point like when they do
- 42:47brachytherapy um like
- 42:49doing the plaque and and just basically
- 42:51kind of have the providers
- 42:52be aware of the like like Doctor
- 42:54Ma said like be aware of the kind of
- 42:56the range of tests available
- 42:58and to try to make sure that you get
- 43:00you know as much information as possible
- 43:02from that one time that you're biopsying
- 43:04yeah no absolutely um
- 43:08that that you know
- 43:09it's we're always up against this in in
- 43:12almost all cancers now right we're getting
- 43:13less invasive and we're trying to do more stuff
- 43:17so we're able to make diagnoses based off of more
- 43:20minimally invasive approaches
- 43:22but the list of things that we need to do with that tissue
- 43:25gets longer every year which is a good thing
- 43:28right it means we're learning
- 43:29more about the cancer but um
- 43:31it's a conundrum because we're we're trying to do less
- 43:34for acquisition
- 43:35but we're trying to do more with what we get
- 43:37so it's a balance yeah absolutely um okay so let's see
- 43:43um
- 43:44this I think we've kind of covered this but just to clarify if a patient was treated a few years back and there is no tumor tissue
- 43:49to biopsy to make the tumor informed Signatera test
- 43:53how can a baseline be established
- 43:55I guess my understanding is you can't establish a baseline
- 43:57at this at this point for the for the um
- 44:00tumor informed test that's right
- 44:02yeah for Signatera we couldn't design you a Signatera
- 44:05in the near term we may be able to design you a latitude
- 44:09okay
- 44:10um let's see
- 44:13Signatera
- 44:14negative like Signatera negative with a positive
- 44:16okay so this is an interesting
- 44:18thing and I've actually had this happen as a patient
- 44:19myself
- 44:20for those of you guys listening if you didn't know I'm also a metastatic
- 44:22uveal patient um so you know
- 44:25this patient is saying what about patients
- 44:26who are CT DNA negative
- 44:28but have a positive tumor burden in the liver
- 44:31like all of them are small less than 8 millimeters
- 44:33do we understand why metastatic
- 44:36uveal melanoma is kind of like a low shedding tumor
- 44:39or like low shedding disease like ultimately
- 44:41why why could you see disease on an MRI in the liver
- 44:44but not be picking up the residual
- 44:46or you know the the Signatera
- 44:48yeah it's a great question um
- 44:51and I'd love to hear Doctor's Ma and Montazeri's
- 44:53thoughts I'll give you you know just briefly it's
- 44:56in the setting where we have
- 44:59radiographically evident disease
- 45:02that's tissue confirmed meaning we know those sub
- 45:05with 8 millimeter sub centimeter nodules are
- 45:09are cancer right and they're not um
- 45:13treatment effect
- 45:14or fibrotic change or what have you right
- 45:17it's actually better to be negative
- 45:18than positive in that scenario
- 45:20right because it means that the
- 45:22biology at least at the time of the blood draw
- 45:26was the biology now was less aggressive
- 45:29uh than the same patient who has a positive result
- 45:33right because remember we're going
- 45:35if we're going in the
- 45:36arm and getting a sample of the peripheral blood
- 45:39right so for the test to be positive
- 45:41that tumor has to be elaborating
- 45:43DNA out into your bloodstream
- 45:46um and that is typically
- 45:47associated with more aggressive behavior
- 45:49right it's doing
- 45:50things it's turning over it's elaborating
- 45:52DNA into the blood
- 45:53at sufficient levels for us to detect
- 45:57when you have disease
- 45:58you could measure and see on a scan
- 46:00but that's not the case that usually infers
- 46:02that at that time the biology is actually less aggressive
- 46:05so it's more indolent so um
- 46:08it in a genome world right
- 46:11when we're when we're using the genome test now
- 46:14I think that scenario would be will be less common
- 46:17because I think we'll be able to detect
- 46:19those indolent low shedding tumors
- 46:22um at even lower levels
- 46:24and so if we come back and we talk in a year or two
- 46:26I might be saying the same thing
- 46:29but now I might be talking about the quantitative
- 46:31value of CT DNA being prognostic
- 46:34rather than positive or negative
- 46:36I hope that makes sense
- 46:37and I'd love to hear Doctor's Ma and Montazeri
- 46:40yeah I agree you know
- 46:41there is a threshold that you can detect the
- 46:44basically those copy numbers in the blood and
- 46:48with a different technology which is always a trade
- 46:51between those sensitivities and how um
- 46:54basically
- 46:55confident you are that what you're catching is real
- 46:58so if you do a deep sequencing you may be able to um
- 47:02catch a very small amount of you know DNA
- 47:06shedding to the blood
- 47:07but that is always a good sign that um the tumors not
- 47:12um you know actively growing and replicating
- 47:15uh too fast to shed it to the bloodstream
- 47:18yeah
- 47:19yeah I think um that's a good problem to have yeah
- 47:23absolutely I mean it's always good to have like a
- 47:26in my opinion
- 47:27we know that having a negative or undetectable
- 47:29level is is very is very good in terms of prognosis
- 47:32but
- 47:33you know I've certainly had those types of scenarios
- 47:35where we have a scan
- 47:37and a biopsy that confirms active disease
- 47:39despite a negative CT DNA level
- 47:42and you know sort of how I like to describe
- 47:44it is you know we we really have a relatively
- 47:46low burden of disease that we just cannot
- 47:49detect it at that very moment in time
- 47:52with the CT DNA assay
- 47:54and so that's kind of how I sort of frame
- 47:56it you know with patients is yes even though
- 47:58we know there's active disease
- 48:00but we can't detect it by by blood
- 48:02that doesn't mean you don't have cancer right
- 48:05you know the other thing I also described and
- 48:07something we've also published you know over the past
- 48:09year or so is that you know the sensitivity of the test
- 48:12you know specifically for melanoma um
- 48:15we've Learned that you know depending on the location
- 48:17of where the disease is um you may have a higher
- 48:20probability of being able to detect it
- 48:22and so for example the most common
- 48:24areas that we published and Learned from is that if it
- 48:26if you have disease in the lung the lymph nodes liver
- 48:30um
- 48:30there's a higher chance of being able to detect it more so than if the disease
- 48:34had essentially popped up in the skin
- 48:37or in the muscle or in the brain for example
- 48:40so I think melanoma probably has an interesting biology
- 48:43where it has the ability to shed
- 48:45DNA with better easier detection than other locations
- 48:49depending on where it is in the body
- 48:51um but as you can imagine
- 48:53I think I think this is really a call to action
- 48:55to to really enhance the technology to better detect
- 48:58you know cancer in the blood
- 49:00and it's very interesting to see you know the companies
- 49:02like Natera sort of developing and
- 49:04and making their test a lot better
- 49:06you know transitioning from an Exome
- 49:08based to a Gome based type of assay
- 49:10so that we can hopefully increase
- 49:12that sensitivity and and make it more reliable
- 49:14for monitoring
- 49:16yeah absolutely
- 49:18um so in terms of this monitoring
- 49:21and kind of like the use of the test
- 49:23one of the questions from our
- 49:25a patient Michelle is asking you know I'm currently
- 49:29like a a stage
- 49:31um or I guess just a high risk tumor profile
- 49:33um so probably a class 2 tumor
- 49:35or just you know higher probability of progression
- 49:37and there's not currently any adjuvant
- 49:39therapy that's being offered for my situation um
- 49:42I've been told by my oncologist that CT
- 49:44DNA wouldn't help
- 49:45as there's currently no treatment available anyway
- 49:48how could I potentially use this test at my stage
- 49:52so I don't know the question if uh um
- 49:58this patient
- 49:59had enucleation or are they talking about you know a
- 50:03um basically
- 50:06a um cell free DNA
- 50:08panel like a genome sequencing panel without um an
- 50:11a tumor tissue
- 50:13it depends on that if we are talking about
- 50:15Signatera um we can use that um
- 50:18in addition to surveillance scans as a method
- 50:21um another layer of information basically for um
- 50:25surveillance there have been some situations
- 50:28that for example
- 50:29if you have a standard of care option like Tebentafusp
- 50:31the sooner you bet
- 50:32you start the treatment you're not gonna lose anything
- 50:35if really there is a very small lesion that um
- 50:38you know um
- 50:40is difficult to biopsy
- 50:43and you have proof that there is a disease recurrence
- 50:47and um start the treatment
- 50:50um on the bright side if you have um
- 50:54negative scans and negative CT DNA that's um you know
- 50:58another layer to reassure you um that
- 51:01there is no evidence that you have cancer recurrence
- 51:04but if you don't have that and
- 51:06do not worry I'm sure your doctors
- 51:09monitoring everything closely
- 51:12well and like I mean
- 51:13five years ago six years ago we didn't have CT DNA
- 51:17as a reliable marker to use as you know like Doctor
- 51:20Montazeri said that extra layer of information
- 51:22so you know it's not that we don't have surveillance
- 51:24available we still have surveillance as patients um
- 51:27we still have Doctor Ma Doctor Montazeri
- 51:29other oncologists who they're prescribing scans
- 51:31like they're doing lab work
- 51:32for other um inflammatory markers like
- 51:36there's still going to be monitoring done so if CT
- 51:39DNA isn't something that can currently be used
- 51:41right now because
- 51:42the tissue isn't available to make the test
- 51:44um that seems like at least in this patient's
- 51:47know in this patient's question that's probably
- 51:49more of the the case is that there's just not any
- 51:51any residual tissue to use
- 51:53um and if you don't have that then
- 51:55you know waiting on that longitude or Latitude
- 51:57test is that what you called it Doctor Krainock
- 52:00Latitude Test um that's an option
- 52:02you know just keep watching for that to come out um
- 52:04keep an eye out in in the Signatera world um
- 52:07we have you know
- 52:09another question that came in asking about um
- 52:11TrilliumBiO and Oncobit who are launching advanced
- 52:14uveal melanoma CT DNA testing um called Oncular
- 52:17like do we know of like like how many companies
- 52:21I guess currently offer
- 52:22CT DNA tests and what's the difference between them
- 52:25and is if it's okay I want to ask Doctor
- 52:27Ma this question
- 52:28because we kind of talked about this in our podcast
- 52:31and I don't know that we can put a number on it for one
- 52:34um
- 52:35I don't know that we could say the exact
- 52:36number of of companies that have a CT DNA test but um
- 52:40Doctor
- 52:40Ma do you wanna go ahead and define the difference like
- 52:43but I I yeah just yeah go ahead and just share
- 52:46what you would like about that and then I'll
- 52:47I'll tease some other answers out of you if I need to
- 52:50yeah absolutely I mean
- 52:52as you guys know I mean I think CT
- 52:54DNA is sort of this hot
- 52:55new thing that we see in the oncology world and
- 52:58we're using this test and it's it's absolutely
- 53:00exploding
- 53:01in the field of how we use it and what settings
- 53:03you know whether it's for treatment monitoring
- 53:06for surveillance
- 53:07and so you can imagine it's definitely become
- 53:09quite a competitive space
- 53:10and I know there's a variety of different companies
- 53:13um that are developing their own CT DNA testing
- 53:16um and so I think you know how I sort of categorize
- 53:19you know sort of the two main types of test for CT DNA
- 53:22there's the tumor informed
- 53:24so just the one you know like Signatera
- 53:25where you actually have to go back to the actual tumor
- 53:28tissue look at the DNA changes
- 53:31and personalize the test for the patient whereas
- 53:34another type of CT DNA test is a tumor agnostic
- 53:37meaning that you don't necessarily
- 53:40need to go back to the patient's tumor tissue
- 53:42but you're actually developing a test
- 53:44based on what we know the mutation is likely to occur
- 53:48because of that specific tumor so for example for uveal
- 53:53melanoma we know about 85 to about 90% of the tumors
- 53:56are GNA11 positive or GNAQ positive
- 54:01and so you can just right off the bat
- 54:03just develop a test that specifically
- 54:05looks for that mutation in the blood
- 54:08so it's another way to do it is
- 54:10um the tumor agnostic method is another method to
- 54:14monitor you know for CT
- 54:16DNA in the blood without relying on tumor tissue
- 54:19you know the person who posed that question um
- 54:23on the question there about TrilliumBiO or Oncular
- 54:26um it is a relatively new test that has recently
- 54:30just become my understanding is commercially
- 54:32available here in the United States um
- 54:34it only just recently
- 54:36became available I think this past month and so um
- 54:39I'm certain there's a lot of excitement
- 54:41and I think many of us in the melanoma
- 54:44the uveal melanoma uh community
- 54:46are excited to learn a little bit more about it but
- 54:49that might be a potential option that
- 54:51we may consider for some of our patients and
- 54:54my understanding is that Oncular or TrilliumBiO test
- 54:57is a tumor agnostic test
- 55:01okay awesome uh I do wanna move on
- 55:03for time we've got about 10 minutes left
- 55:05before we've got a wrap um but just as a you know from
- 55:09from an oncology perspective Doctor Ma Doctor Montazeri
- 55:12what made you start trusting
- 55:13CT DNA enough to use it regularly in your practice
- 55:16well so uh first of all
- 55:20no there is there is no perfect test
- 55:22we don't have any test
- 55:23in medicine that has hundred percent
- 55:26you know a capability to detect um
- 55:28a disease or exonerate that you don't have the disease
- 55:32there is always a um chance that you get a
- 55:36test that is falsely positive or falsely negative um
- 55:40add to um the point that one of um our participants
- 55:44mentioned that they have
- 55:45a small lesions in the liver that CT DNA
- 55:48uh was has been negative it's good it's a good problem
- 55:52on the other hand there are some situations
- 55:54that we have multiple small lesions that are growing
- 55:57and if we rely on the blood test
- 56:01solely we may be falsely reassured
- 56:03that there is no disease
- 56:04or there is no disease progression whereas you can see
- 56:07on the scan that actually
- 56:09there is evidence of new small lesions every time so
- 56:13I I'm happy that there is a very um basically um
- 56:19effective and sensitive tool but um
- 56:21we have to also be cautious not to
- 56:23rely on just one test and um
- 56:26we are still in a phase of collecting
- 56:29information on how to use CT DNA
- 56:32this is not something that has been approved uh
- 56:35for this indication um it is great
- 56:39that you know it's not a financial
- 56:41burden for the patients to get this test
- 56:43but we should also always um
- 56:46continue to use the methods that have been
- 56:49validated based on
- 56:51data that has been more available in the future
- 56:54I'm sure that you know all of these tests are gonna
- 56:58improve even further and until then we should
- 57:01make sure that
- 57:02we use different methods together not to miss anything
- 57:07yeah absolutely yeah Doctor Ma do have anything to add
- 57:10no I think Doctor Montesari um
- 57:13highlighted very important points
- 57:14and I completely agree with her um
- 57:17you know CT DNA testing is something I
- 57:20again offer to my patients
- 57:22um as an optional test at this time right um
- 57:25currently the current
- 57:27standard for you know surveillance
- 57:29as well as treatment monitoring
- 57:31continues to be scans right and while it's exciting
- 57:34particularly where we're at now with using
- 57:36CT DNA testing in the cancer world
- 57:39and we've seen you know approvals
- 57:41and this reaching the guidelines
- 57:43for using as a optional test to compliment imaging um
- 57:48we haven't seen so much of that success quite
- 57:50yet I think with
- 57:51with melanoma and I think part of it is because
- 57:54you know we still need some additional studies
- 57:56you know prospective studies
- 57:58integration into clinical trials so that we know
- 58:02can this test be a reliable and accurate marker
- 58:05to be informative for physicians as well as patients
- 58:09and really inform treatment decisions right
- 58:11um but you know for the time being I think this still
- 58:14continues to be an area of ongoing exploration
- 58:17and how I've been using it
- 58:18um has really been to more so complement
- 58:21you know the testing that I'm doing so biopsies imaging
- 58:24right at the end of the day those are still considered the gold
- 58:27standard um but overall
- 58:29you know my trust in this particular
- 58:31test has really just been you know through experience
- 58:33you know um trying this out on patients
- 58:35who are willing to participate and having this test
- 58:38done
- 58:39and making some really interesting observations and
- 58:42having patients
- 58:43do this gives us an opportunity to publish these
- 58:45results and hopefully validate the use of this test
- 58:47in real world clinical practice
- 58:50yeah I love it um Doctor Krainock what are some of the
- 58:54you know maybe just general unanswered questions
- 58:57about CT DNA and in regards to uveal
- 58:59melanoma that you guys are kind of still trying to figure out
- 59:02um
- 59:02like I guess like do you guys have a good direction of where you're wanting to go with like something like uveal
- 59:06specifically yeah I think um
- 59:11the use cases for uveal
- 59:13share a lot of commonalities with other use cases
- 59:16right we want to know
- 59:17um in patients who have undergone definitive therapy
- 59:20and are in surveillance
- 59:22is there a benefit to using CT DNA
- 59:25during that surveillance
- 59:27um can we either
- 59:29change our approach to surveillance using other tools
- 59:32such that we identify
- 59:33interveneable disease earlier and more often
- 59:36and or can we actually treat on the signal
- 59:39and help patients live longer
- 59:42um and then in patients who are actively
- 59:44being treated for say metastatic disease
- 59:47um kind of like I alluded to in the slides
- 59:50can we be an early warning system for regimen failure
- 59:54and can that early warning system
- 59:55serve as a trigger to change things
- 59:58um and and can that help patients um
- 1:00:01in terms of their progression
- 1:00:02free and overall survival
- 1:00:04um so I think those are really exciting opportunities
- 1:00:06where we think we could help patients
- 1:00:07and improve outcomes um
- 1:00:09you know uveal melanoma as this group knows is a rare
- 1:00:12tumor um so we work with great collaborators like
- 1:00:16um doctors Ma and Montazeri to um generate
- 1:00:20data in sufficient numbers to to drive
- 1:00:22those types of use cases and and drive the adoption
- 1:00:25yeah absolutely
- 1:00:27and I think that you know on the flip side of one of the things that you said
- 1:00:30you know
- 1:00:31CT DNA I think Dr Montazeri you mentioned this
- 1:00:34CT DNA at least in uveal from what you guys are
- 1:00:36are sharing has sometimes been an indication
- 1:00:39and I think even Dr Krainock you mentioned this in your presentation
- 1:00:42that you know if you're seeing um a good
- 1:00:45response to CT DNA even if the imaging is showing
- 1:00:48some level of like small disease progression
- 1:00:50or something like that that can be a reason to
- 1:00:52instead of like jumping off the treatment
- 1:00:54that you stay on it a little bit longer and kind of wait it out see what happens
- 1:00:58um and I think Dr
- 1:00:59Montazeri you mentioned like specifically
- 1:01:00around Kimmtrak that sometimes you don't see the correlation in the scans
- 1:01:03but you are seeing continued benefit you're seeing
- 1:01:07you know that the patient is having a a good
- 1:01:09response in the CT DNA
- 1:01:10and that benefit just kind of shows up in the scans
- 1:01:13later down the road
- 1:01:16um okay so I
- 1:01:17oh man you guys have so many good questions
- 1:01:19I love it but I also haha
- 1:01:22I don't have time to cover all of your guys' questions
- 1:01:24so I wanna see if we can cover just a couple quick ones
- 1:01:27um this is actually I there's two
- 1:01:30two questions I wanna combine and I think Doctor
- 1:01:32Krainock this is probably more for you but um
- 1:01:34is CT DNA as effective at picking up the molecular
- 1:01:38molecular residual disease
- 1:01:39if you don't have a complete
- 1:01:41set of biomarkers from your tumor sample that's
- 1:01:43part one of the question and then I'll ask part two in a sec
- 1:01:47um it's a great question like if we can't design
- 1:01:49against the full complement of mutations
- 1:01:51we typically do uh you
- 1:01:53I guess the first thing I'll tell you is usually we can
- 1:01:56but if we can't um for whatever reason um
- 1:02:00we actually have pretty well preserved
- 1:02:02sensitivity and specificity
- 1:02:04before we really start to drop variants
- 1:02:06and and get down to like you know a three quarter full
- 1:02:09assay so to speak
- 1:02:10we'll start to see drop off at
- 1:02:12patient level performance
- 1:02:13I don't have a ton of data there
- 1:02:15because we can usually do it
- 1:02:17um but suffice to say if this if this
- 1:02:20individual asking the question already knows
- 1:02:22you know that that they can't get a full compliment
- 1:02:25typically
- 1:02:25performance is fairly well preserved in my experience
- 1:02:28until you really get to like
- 1:02:30low variants on the panel mm hmm
- 1:02:33um what about like failed CT DNA because of low plasma
- 1:02:38um what does that mean in terms of
- 1:02:40yeah like that's I guess this is a specific situation
- 1:02:43I don't know if this is unique to the Signatera
- 1:02:45test or just a different CT DNA test
- 1:02:47but they've been told that the CT DNA failed
- 1:02:49because of low plasma in the blood do you guys anybody
- 1:02:52know what that means or do we not really know
- 1:02:55I have not heard of that I have not heard of that
- 1:02:58all I could think of is that the
- 1:03:02volume submitted to
- 1:03:04whether it was us or somebody else was insufficient
- 1:03:07insufficient plasma so just make sure that the kit
- 1:03:10directions
- 1:03:10are being followed whatever test you're using
- 1:03:13follow the directions for the draw on the kit
- 1:03:15and if reach out to the company if they're not clear
- 1:03:19yeah and um I've had that happen
- 1:03:21before I don't think it was
- 1:03:22noted as like it just said no like sufficient
- 1:03:25sample size not obtained like please retest
- 1:03:27that was that was the message
- 1:03:28that I got at least in my in my Natera uh portal uh
- 1:03:32this person wants to know when the Latitude testing
- 1:03:34becomes available I don't know that you had a specific date
- 1:03:36for that yet we we just
- 1:03:38in the in the near future hopefully this year
- 1:03:41okay hopefully this year so
- 1:03:42just you know keep an eye out
- 1:03:43I can't guarantee it but hopefully this year
- 1:03:46okay um let's see
- 1:03:49let's see let's see let's see um
- 1:03:51I do want to cover this really fast
- 1:03:53just from our doctor's perspective
- 1:03:56okay we know that there's you know this kind of
- 1:03:58scanxiety that patients
- 1:03:59go through that like extra layer of anxiety
- 1:04:01uh anxiety related to having scans having your MRIs
- 1:04:05you know ultrasound whatever layer of modality
- 1:04:07that you're having for surveillance um
- 1:04:09Doctor Montazeri Doctor
- 1:04:10Ma how are you guys seeing patients
- 1:04:12kind of emotionally cope with the variability
- 1:04:14right the roller coaster that sometimes CT
- 1:04:16DNA can look like as they're as you're using the test
- 1:04:19more regularly
- 1:04:20that's a great question Danet um and so
- 1:04:23you know over the years I've Learned
- 1:04:25you know especially as I'm asking
- 1:04:27patients if they want to undergo CT DNA monitoring
- 1:04:30and that we know sort of the risks and benefits right
- 1:04:33as we're waiting
- 1:04:34for this test to be you know further validated
- 1:04:36be integrated into guidelines
- 1:04:38you know it still remains an area of ongoing
- 1:04:41you know exploration in its use right
- 1:04:43and so what I often
- 1:04:44say from time to time especially with these
- 1:04:46results is that you know sometimes they
- 1:04:48you have to take them
- 1:04:49a little bit with a grain of salt you know
- 1:04:51say for example
- 1:04:52we've ran into the example where there's active tumor
- 1:04:55in the body on scans and biopsy but it's negative right
- 1:04:59and so those scenarios
- 1:05:00can come up as we're utilizing and
- 1:05:02integrating this test into clinical practice but
- 1:05:05what most
- 1:05:05important thing I also mentioned is you know these
- 1:05:07these results can sometimes
- 1:05:09cause a great deal of anxiety you know kind of waiting
- 1:05:11for that result to come back
- 1:05:13you know about a week or so later um
- 1:05:15can provoke a lot of worry for patients
- 1:05:18and that's something I actually discuss
- 1:05:19quite a bit with patients when we
- 1:05:21decide whether to integrate the test into monitoring um
- 1:05:24but long story
- 1:05:25short is I think after discussing a lot of that I think most patients
- 1:05:28would rather know rather than not you know
- 1:05:31as I mentioned
- 1:05:32it is intended to be used as a complementary test
- 1:05:35and we still need to
- 1:05:37again be very cautious about you know how we
- 1:05:39interpret it because
- 1:05:40again it is still an area of ongoing research
- 1:05:44yeah absolutely Doctor Montazeri
- 1:05:47yeah I totally agree with what Doctor Ma said um
- 1:05:50it is like any test you know
- 1:05:53having a good result is reassuring
- 1:05:56waiting for that brings anxiety you know
- 1:05:59living between the two scans
- 1:06:00and also dealing with the um
- 1:06:03non desirable results um
- 1:06:07it's there is no easy way to reassure
- 1:06:10one person who's going through this um
- 1:06:13it is different of course I'm sure for the patients
- 1:06:15than for um
- 1:06:17the the healthcare providers for the doctors uh
- 1:06:20one thing that I reassure
- 1:06:21them is that you know we are monitoring
- 1:06:24things as closely as possible so
- 1:06:27we are doing whatever that needs to be done
- 1:06:30for this cancer
- 1:06:31I don't want this to take over your life I don't want you to
- 1:06:34you know just um
- 1:06:37sit at home and
- 1:06:39just think about what's gonna happen on the scan
- 1:06:41or what am I gonna do there is nothing else that you need to do other than
- 1:06:45showing up to your appointments
- 1:06:46and we are a team and we can figure this out together
- 1:06:51absolutely I love that um okay well
- 1:06:53I think there's one last technical question um
- 1:06:57and I think that this is the answer to this I can guess
- 1:07:00um but I'm gonna let Doctor Krainock and Doctor
- 1:07:02Ma Doctor Montazeri kind of weigh in here um
- 1:07:05if you're having CT
- 1:07:06DNA done and you're seeing
- 1:07:07like like kind of a low number right like on the scale
- 1:07:10like I know sometimes the results scale um Doctor
- 1:07:13Ma the slides that you showed you had one CT
- 1:07:15DNA test where it showed like a range from zero to 100
- 1:07:18and you had results in there that
- 1:07:20I don't know quite what it was measuring but
- 1:07:22um but like I've seen patients
- 1:07:24with CT DNA that measures you know 150
- 1:07:27and then I've also seen patients
- 1:07:28that measure like 1.5 or point zero three
- 1:07:33do you guys have kind of a a way of determining
- 1:07:36low tumor burden
- 1:07:37using the CT
- 1:07:38DNA test or is that still kind of like an evolving
- 1:07:41research to answer um
- 1:07:43Doctor Krainock I don't know if you've got any
- 1:07:45insights there
- 1:07:46um
- 1:07:49so I kind of set the scale in my mind per patient
- 1:07:54uh huh so I let the patient kind of
- 1:07:57um is it high for them or low for them right so like
- 1:08:00you know 80s high and a thousands high I've seen both
- 1:08:04right so but it but not commonly so I
- 1:08:07I think of it within the patient I don't know across
- 1:08:09patients certainly in melanoma if we have
- 1:08:11enough data to stratify what's high and what's low
- 1:08:14like as a group as a categorical
- 1:08:17um so I think about it more uh within the patient
- 1:08:21yeah and I'm seeing Doctor Ma nodding
- 1:08:24yeah I mean I would say just based on observations
- 1:08:27that I've seen having ordered this test you know um
- 1:08:30on patients in a in a variety of different settings
- 1:08:32and I think um
- 1:08:34of course this is something we need to
- 1:08:35continue to publish on is
- 1:08:37um I I have seen you know some correlation between
- 1:08:41um higher disease burden with a
- 1:08:43relatively higher measurement of circulating tumor DNA
- 1:08:47um whereas you know lower disease burden
- 1:08:49more likely to have lower or even
- 1:08:51you know sort of undetectable
- 1:08:53you know I I don't know if you
- 1:08:54remember Danet when we did our
- 1:08:56webinar where we talked about like
- 1:08:58the analogy of CT DNA right I kind of call it like
- 1:09:02poop right the analogy of calling CT DNA is poop um
- 1:09:06it's basically
- 1:09:07a byproduct that you know essentially you can
- 1:09:09measure right a waste
- 1:09:10product you can measure in the blood
- 1:09:12and so if you have a great deal of active or live tumor
- 1:09:15you're able to measure that much more reliably
- 1:09:18than if you have dead tumor where you're not making
- 1:09:20by product or waste product in this case poop
- 1:09:23then you're not gonna be able to measure
- 1:09:24that that quantifiable a level so
- 1:09:27yeah that's how I've been sort of
- 1:09:28seeing as how CT DNA is and what we're actually
- 1:09:32measuring is we're actually measuring indirectly
- 1:09:35live tumor cells in the body
- 1:09:38yeah that makes sense um kind of on the
- 1:09:41I I apologize I'm kind of teasing
- 1:09:43teasing some tricky questions for you guys but
- 1:09:45have you ever seen in your practice like CT DNA rise
- 1:09:49dramatically and then drop immediately after like say
- 1:09:53Y90 ablation Hepzato like the PHP treatment
- 1:09:57are you are you guys noticing anything
- 1:09:59like that ever and and if so like
- 1:10:02I mean what does that mean
- 1:10:05so the one of the interesting features of CT
- 1:10:08DNA is the half life
- 1:10:10the half life is 30 to 90 minutes
- 1:10:13so you could certainly see a spike I believe
- 1:10:18if you drew when a lot of cell death was going on
- 1:10:22which is exactly what we wanna see right
- 1:10:25but that signal is gonna be gone super quick
- 1:10:28right so 30 to 90
- 1:10:30minute half life means that in 30 to 90
- 1:10:32minutes half of it's gone it's been degraded
- 1:10:35uh and then double that time and it's all gone
- 1:10:37right so yes I believe you can see the phenomenon
- 1:10:40you're describing
- 1:10:41but I think that we don't see it just because the half life is so short
- 1:10:45so you would you would have to really time the draws
- 1:10:48super super specifically
- 1:10:50you would have to be like okay like you drew
- 1:10:53like you did Y90 now you're doing
- 1:10:54a draw and then 30 minutes later do a draw
- 1:10:56that would be an interesting correlation to see
- 1:10:59I just know I've heard of just a few random
- 1:11:01random patients who
- 1:11:02they were like oh my goodness I had
- 1:11:04I had Y90 done and then my CT DNA spiked to like 500
- 1:11:08and then the next time they drew it
- 1:11:10it was all the way down to zero again and obviously
- 1:11:12you know the time between those draws
- 1:11:14was probably a month
- 1:11:15so that was all hopefully you know
- 1:11:17enough time for that like you said that half life to disappear
- 1:11:20but I just I think that's a really
- 1:11:21interesting phenomenon that kind of correlates to the
- 1:11:24the idea of like cancer poop um I guess like my
- 1:11:28mediocre understanding of biology says that cells
- 1:11:31that grow discard
- 1:11:33right they discard cell waste
- 1:11:34and cells that are dying discard cell waste
- 1:11:37so you might have cancer
- 1:11:38poop that's coming from cells that are just actually
- 1:11:40continuing to die or you might have it because it's
- 1:11:43really really actively growing and
- 1:11:45continuing to discard you know everything
- 1:11:47it's not using to grow um
- 1:11:49I don't know if that makes any sense
- 1:11:49yeah and maybe the poop was the cells that already pooped and died ha ha
- 1:11:54together so yeah I agree with
- 1:11:56Doctor Krainock and Doctor Ma
- 1:11:57I also wanted to add and also to your point
- 1:12:00that it depends on what type of treatment
- 1:12:02we're talking about there are some treatments
- 1:12:04that have a gradual effect for example if radiation
- 1:12:06therapy or Y90 we're talking about it doesn't
- 1:12:08you know kill the cells right away uh
- 1:12:11so maybe gradual thing that said
- 1:12:13we have seen this pattern that we actually did um
- 1:12:17CT DNA testing uh
- 1:12:19not necessarily with Natera but
- 1:12:20we were curious to see if this happens with radiation
- 1:12:22and how soon it happens
- 1:12:23and you know usually a few days after radiation we see
- 1:12:27a spike and then um it gradually goes down
- 1:12:30better to do the CT DNA as a baseline right before
- 1:12:34giving the Y90 yeah that makes sense agree
- 1:12:38another example would be you know if you surgically
- 1:12:40remove the tumor you know from the body
- 1:12:42you know we do that on occasion
- 1:12:44from time to time depending on
- 1:12:45stage of disease but you know if you have a high level
- 1:12:48and once you remove the only
- 1:12:50source of where the DNA is coming from
- 1:12:52um you can see that level drop
- 1:12:54you know quite dramatically
- 1:12:55even in some cases it can go down to zero
- 1:12:57yeah absolutely
- 1:12:59alright well okay last question
- 1:13:01for patients who want to know more about CT DNA
- 1:13:03specifically about the Signatera test
- 1:13:05where should they go for information
- 1:13:07and then for a doctor perspective
- 1:13:09if you are a patient who doesn't see Doctor
- 1:13:11Montazeri or Doctor Ma or a patient uh
- 1:13:13a a doctor who currently utilizes
- 1:13:15something like Signatera's test
- 1:13:17how could you go about bringing this up to your doctor
- 1:13:19if you're interested in having this test done so
- 1:13:21doctors keep that in you know park
- 1:13:23we're gonna answer that in a sec Doctor Krainock um in
- 1:13:26in honor of your time I want to let you answer
- 1:13:27that question for where they can get more information
- 1:13:30yeah so you could visit the website
- 1:13:32Natera.com um you can also reach out to me directly
- 1:13:36so my email is my first initial and last name
- 1:13:39MKrainock@Natera.com
- 1:13:46shoot me an email um if you have specific questions
- 1:13:49if you just wanna
- 1:13:51generally learn about the test visit the website
- 1:13:53we have all kinds of patient downloads and brochures
- 1:13:56one thing I wanted to mention
- 1:13:58I saw something about I think you touched on it Danet
- 1:14:00a question about slides
- 1:14:03if you're if the if the patient's talking about slides
- 1:14:06that a pathology department has we can use slides
- 1:14:10so we can scrape the slides
- 1:14:13um so I just don't want to confuse people
- 1:14:15we can't use sequencing done by another lab
- 1:14:19but if it's if you're talking about your tumor
- 1:14:21was sectioned and put on slides like every tumor is
- 1:14:25and it's sitting in a pathology department
- 1:14:27but the blocks been exhausted it's just slides
- 1:14:29if that's what you're describing
- 1:14:30we can use that just FYI
- 1:14:33okay so that's you know worth exploring
- 1:14:35unstained slides right just unstained yeah
- 1:14:38uh one H&E yeah and and the rest unstained
- 1:14:42I think we need at least one H&E
- 1:14:44and it kind of just sounds like if you're not sure
- 1:14:47right that you could have your doctor
- 1:14:48investigate and also connect with Natera yeah
- 1:14:51to just make sure that that's a good idea you know
- 1:14:53that they can clarify
- 1:14:54like okay if there's some level of disease
- 1:14:56sample available is this
- 1:14:58usable for the test or not and just kind of let them
- 1:15:01that's a great point it's not up to the patient to go figure that out if you're
- 1:15:04interested our our team will will will
- 1:15:06find out for sure that's a really good point Danet
- 1:15:09awesome okay um Doctor Montazeri Doctor Ma patients
- 1:15:13who don't see you or don't see a doctor
- 1:15:15who uses Signatera or a CT DNA test
- 1:15:17what would you say to them
- 1:15:18bringing this to their doctor
- 1:15:19and like kind of how they could approach that
- 1:15:22I guess I could start um you know um
- 1:15:25so I've been a very heavy user
- 1:15:26of circulating tumor DNA in my practice but
- 1:15:29you know I would say not every provider
- 1:15:31is you know even familiar
- 1:15:32with it you know and so having this sort of like
- 1:15:36uh webinar here podcast
- 1:15:37I think a lot of patients
- 1:15:38are starting to learn about what are their options
- 1:15:40you know in terms of like cancer monitoring
- 1:15:43and so you know for patients who are interested in
- 1:15:45doing things like CT DNA monitoring
- 1:15:47whether it's for surveillance or treatment monitoring
- 1:15:50I'd say start off by at least asking your provider
- 1:15:52you know I think nowadays with CT
- 1:15:55DNA being so heavily used
- 1:15:56you know in a variety of different settings
- 1:15:59not just melanoma but for other cancers
- 1:16:01I think every provider at this point is at least familiar
- 1:16:03with it
- 1:16:04and it's an opportunity for them especially if they don't have it available in their practice
- 1:16:08to to push themselves to look into it and potentially
- 1:16:11bringing it in as an option to their clinical practice
- 1:16:13and so um as usual you know um
- 1:16:16Doctor Montazeri and myself
- 1:16:17we're we're primarily at academic centers
- 1:16:19you know where we're always pushing
- 1:16:20the limits in terms of research innovation um
- 1:16:24but you know it's never wrong to to get great
- 1:16:26care as well as in the community
- 1:16:27and even though they may or may not have the test
- 1:16:29available
- 1:16:30it's always reasonable as a patient to always ask
- 1:16:33what are my options
- 1:16:34can I do something that is available out there especially
- 1:16:37for something like Signatera
- 1:16:39which is commercially available yeah absolutely
- 1:16:44okay
- 1:16:44well you guys thank you so much for your participation
- 1:16:46as our audience we could not do this without you guys
- 1:16:49you guys have been a wonderful audience
- 1:16:50if you guys are listening to this recording
- 1:16:52on our edited YouTube channel then
- 1:16:55please make sure you're dropping those questions
- 1:16:56in the description or in the the YouTube chat later
- 1:16:59and we will do our best to come back and answer those questions
- 1:17:02but for now let's give a huge thanks to Doctor
- 1:17:04Krainock Doctor Montazeri and Doctor
- 1:17:05Ma for being our guest
- 1:17:06speakers here and just having this discussion with us
- 1:17:09um and again huge thanks to our sponsors um
- 1:17:12Natera Castle Bio Sciences Aura Bio Sciences
- 1:17:16Delcath Systems Ideaya
- 1:17:17Biosciences and Immunocore for making sure that our
- 1:17:20um our webinar can happen
- 1:17:22and we look forward to seeing you guys for quarter
- 1:17:23three um in the meantime
- 1:17:25we've got ASCO to look forward to this summer
- 1:17:27that's a lot of the doctors are heading
- 1:17:29there I think all three of these doctors
- 1:17:30are actually heading to ASCO next week in Chicago
- 1:17:33if you're not familiar ASCO is one of the biggest um
- 1:17:35cancer
- 1:17:36like research conventions where people are presenting
- 1:17:38you know abstracts
- 1:17:39they're presenting research they're presenting
- 1:17:41clinical trial data if we have any that's matured
- 1:17:44like all of those kinds of fun things so stay tuned
- 1:17:46with A Cure In Sight
- 1:17:47we've got Eye On Research happening at the end of July
- 1:17:49maybe beginning of August
- 1:17:51um so make sure to stay tuned
- 1:17:52for that and we will see you guys next time bye guys
- 1:17:56Bye everybody thanks Bye thank you