Latest / The Eye Believe Podcast / Eye on COOG | What's New in Uveal Melanoma Risk Reports?

Transcript

Eye on COOG | What's New in Uveal Melanoma Risk Reports? · The Eye Believe Podcast

0:00
hey all of our lovely friends
0:01
lovely omies thank you so much for joining us today
0:04
for our Eye on COOG webinar
0:06
if you guys are joining us from the online space
0:09
anywhere around the world really
0:11
please drop a hello in the chat
0:13
tell us where you're from
0:14
maybe tell us your diagnosis date
0:15
if you feel like sharing
0:16
kind of where you are in your journey
0:18
but we are thrilled to bring you guys Eye on COOG today
0:21
and we have about an hour and a half max
0:23
two hours
0:23
where we're gonna be covering some really good content
0:26
of what's new in the uveal melanoma risk reports
0:29
and this uh
0:29
webinar is presented by Castle Biosciences
0:32
and co sponsored by Ideaya Immunocore
0:35
Aura Biosciences and Delcath
0:37
so we can't thank our sponsors enough
0:39
thanks for being here with us
0:40
in order of appearance
0:42
we have Dr. Amy Schefler who's joining us
0:45
and we also have Dr. Basil Williams
0:47
and Dr. Kat Alsina from Castle Biosciences
0:50
uh we are thrilled to have all of them here
0:51
and thrilled to have this presentation
0:53
uh up first
0:54
we're gonna have our first segment
0:55
covered by Doctor Schefler
0:57
like I said huge thanks to our sponsors
1:00
first up speaker
1:01
is from the Collaborative Ocular Oncology Group
1:03
and uh this is Doctor Amy Schefler
1:06
she's an ocular oncologist
1:07
at the Retina Consultants of Texas
1:08
and I'm gonna let her take it away
1:10
alright so thanks everyone for joining
1:12
hopefully this will
1:12
be super educational and helpful for everyone
1:16
I think the plan we're gonna have here is I'm gonna um
1:19
go over some background and then um
1:22
we're gonna take all the questions at the end
1:24
but my co panelist here will monitor the chat
1:27
and if there's something urgent
1:28
they'll kind of nudge me and I'll stop
1:29
and answer any critical questions that we have
1:32
so thanks to A Cure In Sight
1:34
of course for organizing this
1:35
and for um
1:37
Castle for asking Doctor Williams and me to join
1:40
it's an honor to be here with you guys
1:43
so I'm gonna give everyone on the zoom
1:45
a little background about COOG
1:48
and the history of COOG
1:49
and kind of where we are with it today
1:52
so this is a photo of all of my friends
1:59
um this is a picture of all of us
2:00
at our collaborative meeting
2:03
um actually
2:04
in 2025 I think this is the 2025 picture
2:08
in Dallas we all get together once a year
2:11
and talk about all the research that we're doing
2:13
the work that we've done already
2:14
the work that we are hoping to do in the future
2:18
some of the
2:18
definitely brightest minds in the uveal melanoma space
2:21
are always at this meeting
2:22
is one of my favorite meetings every year
2:24
and where we've hatched some of our very best ideas
2:26
and this meeting is coming up next month
2:28
so we're all looking forward to it
2:29
so just to give everyone a background on um
2:32
where this started and where we're going
2:35
many folks around the country
2:36
researchers have been looking at um
2:38
the genes involved in uveal melanoma
2:39
ever since the early 1990s
2:41
actually
2:42
cytogenetics which is the study of looking at um
2:45
chromosomal breaks
2:46
and missing pieces of chromosomes and abnormalities
2:49
started all the way back in the early 1990s
2:51
but it was a long time before people kind of realized
2:53
you know how researchers realized
2:56
how could you take that information and
2:58
and sort of uh
3:00
use it in a way that was um
3:02
valuable for a clinical setting
3:04
so it was kind of in the early 2000s that um
3:07
Bill Harbour in his lab um
3:09
at Washington University in Saint Louis
3:11
started looking at the expression
3:13
of some of the really important genes
3:15
involved in this tumor
3:16
and kind of looking at full genome sequencing
3:19
looking at all the genes in the human genome
3:20
and saying hey
3:21
which of these are really
3:22
critically involved in this particular tumor
3:25
and eventually they honed in on 12 particular genes
3:28
which seemed to be especially important
3:30
in terms of whether they were overexpressed
3:32
or underexpressed meaningfully in this tumor
3:34
and over time and over years of hard work
3:37
kind of put together this panel of 12 um
3:39
critical genes that seem to kind of define
3:42
which of these tumors were really aggressive
3:43
and which were not so aggressive
3:45
so in order to kind of verify those findings
3:48
the COOG1 study launched um
3:49
in the mid 2000s to try to look at this panel and see if um
3:53
it was really predictive of um
3:55
how aggressive these uveal melanomas um
3:57
were and that study was published
4:00
and led to the kind of CLIA (Clinical Laboratory Improvement Amendments) approval
4:03
the lab certification of the testing
4:04
and the widespread use of it clinically
4:07
and so it's a 15 gene signature test
4:09
12 what are called experimental genes
4:11
meaning the genes that are important
4:13
and three control genes um
4:15
and that test is now you know
4:16
ordered as everyone knows
4:17
clinically through Castle Biosciences
4:19
and the brand name is the DecisionDx-UM
4:21
test and
4:22
you know
4:23
it has been widely used throughout the United States
4:25
and other parts of the world um
4:27
since then
4:28
and then as the use of that test picked up and evolved
4:31
many many investigators
4:33
published their clinical experience with it
4:35
and then over time
4:36
other genes were discovered to kind of
4:38
be independently important
4:40
in 2009 2010
4:42
a couple of groups around the country
4:44
found that a gene called BAP1
4:45
was particularly aggressive
4:46
and involved in when it was mutated
4:49
when it was kind of misprinted in the human genome
4:52
leading to a particularly aggressive form
4:54
of this disease and other genetic mutations also um
4:58
were you know
4:59
learned to be important as well
5:01
in 2016
5:03
was the first publication about what's called prame
5:05
or preferentially expressed antigen in melanoma
5:08
which is a tumor antigen
5:09
that is normally only expressed in healthy tissues
5:12
believe it or not in the testis and the ovary
5:14
and sometimes the endometrium
5:17
but when it's abnormally expressed
5:19
is a marker of also tumor aggression
5:21
both in uveal melanoma and other tumors
5:23
so that kind of became part of our algorithm
5:25
and then finally all the way to the current day
5:28
um in 2017
5:29
we launched kind of the second phase of the study
5:32
which was finally just published this year
5:34
so um
5:34
as many on the zoom know this is kind of the um
5:38
clinically sort of the approach that we take now
5:40
as an oncologist you know
5:42
we see patients in the clinic
5:43
and we identify that they have a uveal melanoma
5:47
um we speak with the patient
5:48
counsel them explain to them that um
5:50
we're planning on doing treatment
5:52
which most of the time in United States
5:54
involves either plaque brachytherapy
5:55
or external beam therapy or enucleation
5:58
at the time of that therapy
6:00
whatever we choose we do a biopsy
6:02
all wrapped up into that same surgery
6:04
in which we send the specimen
6:06
for all of these tests that I just mentioned
6:08
and then typically you know
6:10
anywhere from two to four weeks later
6:11
we get that information back from Castle
6:13
and counsel the patient with that information
6:16
there have been other approaches
6:17
that have been taken by some investigators
6:19
to try to kind of have clinical surrogates for this
6:22
like can we just look at the tumor size
6:24
you use AJCC staging
6:26
but the challenge with a lot of those other systems
6:28
is that there are often outliers
6:31
and we're going to show you some examples of this
6:32
later in the zoom so
6:33
some patients with really big tumors
6:35
will actually have very non aggressive biology
6:38
and some patients with very small tumors
6:39
will actually have very aggressive biology
6:41
so it's important to look at the genes in the tumor
6:44
cause that's what really drives our understanding
6:48
so with this biopsy that we do intraoperatively
6:50
we get information from these three key tests
6:53
so the 15 gene expression profiling
6:55
which I mentioned
6:56
which is our strongest and most powerful
6:57
and most predictive test that um
6:59
we've had for the longest
7:01
that's been the most proven
7:02
and the most prospective studies
7:03
kind of the gold standard in science
7:05
then we get results from our prame expression test
7:08
the antigen that I mentioned
7:10
and the readout from Castle will
7:11
state that that's either positive or negative
7:13
it's if it's positive
7:15
it means that that antigen
7:16
is being expressed by the tumor cells
7:18
in that particular patient's test
7:19
and are assigned a sign of more aggressive behavior
7:22
and then
7:23
what we call the next generation sequencing test
7:25
which helps us look at particular mutations
7:27
in the tumor talk about that more in a second
7:29
so this is an outline of those three tests
7:32
each patient will get a readout that says
7:34
basically that their tumor is either low risk
7:36
class 1 or high risk class 2
7:39
and again what this riskiness is
7:40
is the riskiness or likelihood
7:42
that that tumor
7:43
may or may not have gotten out of the eye
7:46
before the time of diagnosis of the tumor
7:49
but I have a situation
7:50
where there are too few cells to see
7:52
on the imaging test that has often been obtained
7:54
before the treatment of the liver
7:56
so for example
7:56
if one or two or three cells have gotten out
7:59
um
7:59
those cells won't be visible on the MRI or the CT scan
8:02
cause we really need 750,000 cells
8:04
or million cells to make it visible on the MRI
8:07
um but there might be one or two or three
8:09
and if the tumor is designated as class 2
8:12
we know okay
8:13
there's a chance we might be in that situation
8:15
and then the prame also helps us understand
8:17
what's the likelihood that may have happened
8:19
as well and then we look at these mutations
8:21
so there are seven mutations on the readout
8:23
from the report from Castle
8:25
these first four here that say uveal melanocytic
8:28
driver mutations
8:29
are actually what are called initiating mutations
8:31
so those are mutations that help us understand that
8:33
in fact our biopsy did come from a melanocytic lesion
8:36
that it came from a uveal tumor of melanocytic origin
8:40
and it helps us know that
8:41
in fact this tumor specimen was of good quality
8:44
and from the correct tissue type
8:46
so that we didn't send retina or vitreous
8:50
or normal choroid but then
8:52
in fact we did send cells from that patient's tumor
8:55
and then these other three mutations here
8:57
EIF1AX
8:58
SF3B1 and BAP1
8:59
help us understand also the level of riskiness of the
9:04
that the tumor may have metastasized
9:06
prior to the time of doing the treatment
9:09
so EIF1AX is associated with a low mutation
9:12
low risk of metastatic disease
9:14
so more associated with class 1
9:16
SF3B1 is an intermediate mutation
9:19
and BAP1 is a very high risk recruitment mutation
9:22
in most cases associated with a class 2 genotype
9:26
so this is the data from the COOG1 study
9:28
that very first study
9:29
that kind of established this test as clinically valid
9:33
and scientifically valid and essentially
9:35
what this diagram shows is that patients with class 1
9:38
in the overwhelming likelihood of cases
9:40
survive and go on to live many years
9:42
without metastatic disease
9:43
whereas patients with class 2
9:45
are more likely to develop metastatic disease
9:47
over time now
9:48
this is just an algorithm
9:50
a statistical algorithm so
9:51
it's not that every single class 1 patient
9:53
lives forever or every single class 2 patient
9:55
dies of metastatic disease
9:56
but more statistical likelihood
9:58
that we use to counsel patients
10:00
and many many investigators
10:02
as I mentioned have published their data
10:04
and their experience with these tests
10:06
ever since the time of their development in the lab
10:10
showing that it's you know
10:11
both clinically and scientifically valid
10:13
the COOG1 study you know
10:15
all the way back in the mid 2000s
10:17
all the way to the COOG2 study
10:19
at the current day
10:21
so how do we kind of interpret these biomarkers and
10:24
and counsel patients we're gonna
10:26
kind of give you some examples of cases at the end
10:28
that I think
10:28
will help give more color as to how we do this
10:31
but as time evolves
10:32
and these tests become more and more used
10:34
on a very large scale clinically
10:36
we've become more and more savvy at how to kind of
10:38
integrate the information
10:39
from all three of these tests
10:41
and kind of make it useful for patients
10:43
and we'll illustrate that again in a little bit
10:46
so all of this work has really been um
10:49
very collaborative
10:50
and it's important with rare diseases like this to
10:52
to kind of leverage the you know
10:55
intelligence and clinical experience
10:56
and scientific work of everyone across the country
10:59
is dedicated to patients with these diseases
11:02
and this is the group of COOG2 investigators
11:03
across the country
11:04
I'm sure many of the patients on the zoom
11:06
know these folks
11:07
and have had many intimate interactions with them
11:09
being taken care of by all these amazing clinicians so
11:12
and
11:13
these are all people that Doctor Williams and I call
11:15
colleagues and friends every day
11:16
so um
11:17
these are the investigators who contributed patients
11:19
to the COOG2 study and contributed intellectually
11:22
to the understanding and um
11:24
scientific advancement
11:25
of what we learned from the study
11:26
so um
11:27
there were 26 centers in the study
11:29
all across the United States and Canada
11:30
we had many many
11:31
many zooms on Saturday mornings early
11:33
early in the morning um
11:35
on our executive committee
11:36
discussing all of our data
11:38
and coming to understand it and analyzing it
11:40
and so forth it was hundreds and hundreds
11:42
and hundreds of hours of work
11:43
on behalf of our patients
11:44
so there have been two studies published so far um
11:47
from this data set um
11:49
both uh
11:50
this last year and this year um
11:52
it's too kind of
11:53
scientifically dense to get into all of the details
11:55
but essentially the first report
11:57
revalidated the value of prame
11:59
in understanding the level of aggression
12:01
of these tumors and
12:02
started to dive into the use of next generation
12:04
sequencing and the second report
12:06
which is literally like
12:07
in the process of being published right now um
12:10
or coming out right now um
12:11
talks about the value of next generation sequencing
12:14
and there'll be many many
12:15
many more papers
12:16
from this massive data set of over 15 patients um
12:19
coming out over the next year or two
12:20
which will slowly kind of leak out into our like
12:23
everyday clinical um
12:25
experience and what we're able to counsel patients with
12:28
um day to day
12:30
so many many years of
12:32
of experience
12:32
have gone into making this data useful for patients
12:36
so I'm gonna turn it over to Kat Alsina from Castle
12:39
who's gonna kind of take it from here
12:40
and talk about these reports that we give our patients
12:43
and kind of how we use them day to day
12:46
and the new version of it that this
12:47
that has come out um
12:49
as a result of the COOG2 study
12:50
and I'm kind of understanding that report
12:54
that your doctor has given you
12:55
all right um
12:56
well thank you
12:57
Doctor Schefler
12:58
that was a beautiful overview of the history of COOG
13:01
and give us a good high level sense of
13:03
of what the first two studies have covered
13:06
I'm gonna focus in now about how some of the um
13:10
results from the first COOG2 report
13:13
are being integrated into Castle's clinical reporting
13:16
and into national guidelines for managing patients
13:20
as Doctor Schefler discussed
13:22
the COOG2 study is really
13:24
the largest and most comprehensive study to date
13:27
that has looked at Castle's three tests
13:30
for uveal melanoma and the first report um
13:34
the doctor Schefler mentioned
13:35
focused on prame
13:37
and what prame adds to the information
13:39
from the 15-GEP test
13:42
Castle's prame test has been available since 2016
13:46
and the COOG2 study cohort included over 1500 patients
13:51
that were tested with both the
13:53
the GEP test and the prame test
13:55
so that's a really large cohort of patients
13:58
for such a rare disease it's an incredible
14:00
collaborative effort
14:01
to get those patients enrolled into the study
14:03
but the most important finding from that study gives us
14:07
really the first strong data around prames
14:10
contribution to metastatic risk
14:13
and I'm gonna show uh
14:14
some of the data in in just a second
14:16
but really the study found that prame works to kind of
14:19
fine tune risk for both class 1 and class 2 tumors
14:25
um but before I go into the data
14:27
I thought I'd start with a little more background
14:29
about prame
14:30
Doctor Schefler already kind of covered some of this
14:32
but um
14:33
Prame stands for preferentially expressed antigen
14:36
in melanoma
14:37
it's a gene that is usually not found in many normal
14:41
adult tissues but in some cancers
14:43
like uveal melanoma prame levels are abnormally elevated
14:47
so um
14:48
when prame gets turned on in uveal melanoma
14:51
that might indicate a higher chance
14:53
of an aggressive tumor that's more likely to spread
14:56
and so back in 2016
14:57
there was a lot of interest around prame
15:00
because of some early studies uh
15:02
from Doctor Harbour's lab that suggested that
15:05
you know increased expression of prame
15:07
was associated with more aggressive uh
15:09
uveal melanomas and so um
15:13
you know specifically
15:14
this seemed to have more of an impact
15:16
in the class 1 tumors
15:17
with class 1 prame positive tumors being more risky
15:20
than class 1 prime negative tumors
15:22
but anyway in 2016
15:24
Castle started offering this prame test uh
15:27
based on those early retrospective studies
15:29
but the COOG2
15:31
study was is really the first prospective
15:34
so forward looking study to evaluate prame in a large
15:38
uh group of patients
15:41
so this is what the main data looks like
15:44
from that first COOG2 study on prame
15:47
so the left is a graph of metastasis free survival
15:50
where you can see
15:52
there's a separation of four distinct groups
15:55
the top two lines there are class 1 tumors
15:59
which separated
16:00
depending on whether they were prame negative
16:02
so that's the dark blue line at the top
16:04
or whether they were prame positive
16:06
which is the teal line right underneath it
16:09
and then similarly the
16:10
the bottom two lines are the class 2 tumors
16:12
so you can see that those uh
16:14
class 2 tumors
16:15
also separated out into two distinct groups
16:18
depending on whether they were prame negative
16:20
so that's the orange line or prame positive
16:22
and that's the the red line
16:24
so essentially you know
16:25
both class 1 and class 2 tumors were stratified
16:29
depending on whether they were prame negative
16:31
or prame positive and so that was an important finding
16:34
that prame status is able to modify the GEP
16:38
risk result and so on the right
16:40
you can see a summary of what that new data tells us
16:43
and what it means for patients
16:45
the class 1 prame negative tumors
16:47
have the lowest risk of metastasis at five years
16:50
and in the COOG2 study
16:52
about 96% of patients were metastasis free
16:56
in that group at five years
16:58
the class 1 prame negative tumors
17:00
have an intermediate risk of metastasis
17:02
with 81% of those patients metastasis free at 5 years
17:06
and then the class 2 tumors remain the high risk group
17:10
regardless of prame status
17:11
but there is a meaningful difference
17:13
between class 2 tumors that are prame negative
17:16
and class 2 tumors that are prame positive
17:18
so the class 2 prame negative tumors do better
17:20
with 58% metastasis free at five years
17:23
compared to 45% metastasis free in the class 2
17:28
prame positive group so
17:30
these findings were hugely important to us
17:33
here at Castle and based on those findings
17:36
we felt pretty confident
17:37
that it was time to update our reporting
17:40
so earlier this year
17:41
we rolled out updates to both our GEP
17:44
test report and our prame test report
17:47
those two uh
17:48
results are are still reported separately
17:51
but we have updated them
17:53
to include the new risk data from the COOG2 study
17:57
and so the most important data is gonna be found on
18:00
prame report which is shown on the right
18:02
it highlighted in orange
18:04
and that's where we've included the risk estimates
18:06
that are associated with the combined groups
18:09
so the GEP and prame
18:11
when put together gives you those uh
18:13
those four different groups
18:15
with specific risk estimates
18:16
the other really exciting update in 2025
18:19
was a recent change to the uveal melanoma guidelines
18:24
and so the guidelines are updated
18:26
whenever new and important data is published
18:28
that is considered to be practice changing data
18:32
so after the prame findings were published
18:34
the Uveal Melanoma Guidelines Committee reviewed that data
18:38
and updated their management recommendations
18:41
for patients so
18:42
the guidelines now recommend using prame status
18:46
alongside the GEP class results
18:49
to help better tailor surveillance plans for patients
18:53
and so this slide just
18:54
kind of summarizes
18:55
what that management pathway looks like now
18:57
when incorporating both the GEP
18:59
class and prame status together
19:02
and so you can see you know
19:03
different surveillance plans are recommended now
19:07
based on those combined results
19:09
with the class 1 prame negative tumors
19:12
following the lowest intensity management plan
19:14
with image based surveillance every 12 months
19:17
and the class 1 prame positive patients
19:20
which is this intermediate risk
19:23
following slightly you know
19:25
higher intensity surveillance plan
19:27
with imaging every six to 12 months
19:29
and then the higher risk class 2 patients
19:31
following the highest intensity management
19:33
with surveillance every three to six months
19:36
and they may have the opportunity to enter um
19:40
adjuvant clinical trials to
19:42
to try and prevent
19:43
or delay the onset of metastatic disease
19:46
so these were really um
19:47
exciting updates that happened over the past year
19:50
and I think particularly these changes to the
19:52
the guidelines really represent a huge step forward
19:56
in personalizing care
19:58
based on each patient's unique tumor biology
20:02
so with that
20:03
I'm going to turn it over to Doctor Williams
20:05
who's going to talk about the second COOG report
20:07
that focused on the value of DNA mutations
20:11
thanks so much
20:11
There've been two fantastic presentations so far
20:14
thanks to
20:15
Danet from A Cure In Sight and Kat Alsina from
20:18
Castle Biosciences I'm excited to be here with
20:20
you today and we've had two fantastic talks already
20:23
and I'm gonna be talking a little bit about uh
20:26
the role of DNA mutations um
20:28
and mutation sequencing um
20:30
and the information beyond uh
20:32
GEP and prame
20:34
and so you know
20:35
Doctor Schefler did a fantastic job
20:38
kind of highlighting the DecisionDx-UM
20:41
testing for GEP and for prame
20:43
and Kat Alsina just talked about that a little bit more
20:46
and I'm going to be focusing a little bit more on
20:48
DecisionDx-UMSeq
20:50
and this is a custom DNA sequencing test
20:53
that looks at the most commonly associated genes
20:55
with uveal melanoma
20:57
and we know that uveal melanoma has a lower
21:00
number of mutations than other cancers
21:02
and this is kind of one of the reasons uh
21:04
why it may be more difficult to treat
21:06
than other types of conditions
21:08
including skin melanoma um
21:10
and so you can see some of these mutations here
21:14
and we'll go into a little bit more detail about them
21:17
so um
21:18
what do these uh
21:19
mutations tell us we wanted to kind of understand
21:22
what does the role that these mutations play
21:25
in our understanding of uveal melanoma
21:27
in our understanding of prognostication
21:29
basically meaning the risk um
21:32
of metastatic disease developing in the future um
21:35
and so this was studied in the COOG2 study group
21:38
and there were over 1100 um
21:40
patients evaluated for um
21:43
these mutations and here you can see uh
21:46
the report uh
21:47
that looked at these DNA mutations and um
21:51
this is the preprint version that's available
21:53
and it's going through some final peer review um
21:56
but should be expected to be uh
21:58
published completely um
21:59
in the very near future and kind of before I go into uh
22:04
some of the discussion on that paper
22:06
we'll give you a little schematic so you can understand
22:09
uh the role of these mutations in melanoma
22:12
and I'm really happy that I went after uh
22:15
Kat Alsina
22:16
because I only had the eight pack of crayons growing up
22:19
and so I wasn't quite sure what color the
22:21
SF3B1
22:22
mutation was and now I know it's teal
22:24
so that's a helpful for me
22:26
so basically what you can see here
22:28
is that there is kind of an order to um
22:31
these seven mutations
22:32
and so you start out with a normal melanocyte
22:35
all the way on the left so this is a cell um
22:38
that everyone has
22:39
and then it can develop one of these four mutations
22:42
in orange and when you develop one of these mutations
22:45
it turns uh
22:46
the melanocyte can turn into a nevus
22:48
and so that basically is like a mole um
22:51
at that point that's still a benign lesion
22:53
and then it can undergo a second set of mutations
22:56
either an EIF1AX in blue
22:58
an SF3B1 in teal or a BAP1 mutation in red
23:02
and that's what turns it into a malignant melanoma
23:05
and gives it the possibility of developing metastasis
23:10
and so you know
23:11
you can see here that the mutations in orange
23:14
they're found in almost all of the tumors
23:16
but they don't give us prognostic information
23:18
so they do not help us identify or differentiate
23:21
which tumors are more likely
23:24
to spread to other parts of the body
23:26
but but
23:26
it is really helpful for us to understand
23:28
that this is a melanocytic tumor confirmation
23:31
basically that when you've done your biopsy
23:33
you have tumor material
23:36
and this is something that is extremely helpful
23:39
for physicians and patients alike
23:40
to make sure you know
23:42
that the biopsy sample
23:43
was from the tissue that you wanted to test
23:47
and then you have your second set of mutations
23:49
that we mentioned
23:50
and these are found in about 60% of tumors
23:54
and EIF1AX
23:55
and SF3B1 are most likely found in class 1 tumors
24:00
and they're
24:00
so they're associated with a lower risk of metastasis
24:05
whereas the BAP1 mutation
24:07
is more commonly found in class 2 tumors
24:10
and obviously therefore has a higher risk of metastasis
24:14
but when we look at this
24:15
does this provide any additional information
24:18
to what we found with GEP
24:19
and prame and it turns out
24:21
it does not add additional risk information to GEP
24:24
and prame and so basically
24:25
what that means is
24:26
we are able to focus on the class and prame status
24:31
and that will give us the most information
24:33
and that we need to determine what the risk is
24:36
of metastatic disease in the future
24:38
does that mean that these mutations are not helpful
24:42
no they are helpful
24:43
they actually do provide information for us
24:45
what kind of information do they provide
24:48
um so we know they're not as accurate as GEP or
24:50
prame for risk assessment
24:52
but it does help us to um
24:54
understand our tumor sampling confirmation
24:56
which we talked about
24:57
making sure that you have tumor sample there uh
24:59
we also know there is diagnostic confirmation so um
25:02
if you have a mutation
25:05
one of the orange mutations
25:06
a G protein mutation in the beginning
25:08
we know it's a melanocytic tumor
25:10
so it is uh
25:11
along the lines of a nevus
25:13
at the very least
25:14
when you have a second set of mutations there
25:16
we know it's a melanoma and so that can be helpful to
25:19
uh confirm the diagnosis
25:22
we can also get some early information
25:24
about germline or inherited mutations
25:26
uh Doctor Schefler and
25:28
and the team from Castle Biosciences
25:30
helped to put together a little study um
25:32
looking at patients who have a BAP1 mutation
25:35
and then being able to test those
25:38
to see if they have a germline
25:39
or an inherited mutation
25:41
which makes them more likely to develop uveal melanoma
25:43
and potentially other cancers
25:45
so this is something that's helpful in that it is also
25:48
these mutations are also helpful
25:50
in terms of qualifying patients for clinical trials
25:53
so we can understand which patients have higher risk
25:56
and can benefit
25:57
from some of the clinical trials that we have going on
26:00
now
26:01
we also know that a number of patients have asked
26:03
well if I get a biopsy
26:04
what are the chances
26:05
that we actually get sufficient information
26:07
that we get enough information from the tumor
26:10
to be able to to
26:12
to kind of gain information about prognosis
26:16
and you can see here that the results from the biopsy
26:19
of all three of these samples
26:21
of all three of these tests taken together
26:23
are extremely high
26:25
and so this is not just from the COOG test
26:28
this is actually from Castle's database
26:30
and you can see over 3700 patients are assessed
26:34
and when we're looking at GEP
26:35
testing for class 1 and class 2
26:37
you can see that there was 97% uh
26:40
of those lesions had a successful report
26:42
um for prame
26:43
it was 99% had a successful report
26:46
and when you're looking at um
26:47
the DNA mutations and the next generation sequencing uh
26:51
panel test you can see 97% of successful reports
26:55
and so basically
26:56
it means that when you get the biopsy done um
26:58
and it is sent out for analysis
27:01
you're getting extremely high rate
27:04
of sufficient material and successful reports
27:07
so this is good news for when the biopsy is done
27:11
and so basically
27:13
it's extremely unlikely that if you get testing
27:15
you will not have a result
27:17
because there's insufficient information
27:20
and so at this point
27:21
I will kind of turn it over to the group a little bit
27:24
and we'll go over some case examples
27:26
and have a panel discussion
27:28
and then kind of go through some of the Q&A
27:31
and so I think you know
27:33
our first case here is a case of Doctor Schefler's
27:36
and uh I can have her uh
27:39
take it away thanks
27:41
Doctor Williams um
27:42
great job reviewing um
27:45
next generation sequencing
27:47
alright so um
27:48
we thought we would share some cases of patients
27:51
with you all
27:52
to kind of help understand
27:53
kind of day to day
27:54
how we as clinicians use this information to help us um
27:58
counsel our patients um
28:00
some of this is kind of scientifically
28:03
uh nitty gritty
28:04
and hopefully some of it will feel pretty accessible
28:06
and of course feel free to uh
28:08
ask any questions in the chat as we go along
28:11
um so this is a patient of mine
28:13
who's a 63 year old gentleman
28:15
who came to me about almost five years ago
28:18
with a large um
28:19
uveal melanoma
28:20
that would be considered very aggressive
28:22
based on traditional staging methods
28:24
based only on size
28:26
this is a photo fundus photograph
28:27
so photograph of the back of his eye
28:29
and actually this
28:29
there's a little bit of an error in the slide
28:31
this is actually not the photograph
28:32
of what he looked like when he first came
28:33
to me but when he first came the
28:36
the tumor was actually um
28:38
obscuring a view of his entire optic nerve
28:40
and his macula completely
28:42
and this ultrasound
28:43
is the correct ultrasound of the eye
28:46
when he presented
28:46
so this is what we call collar button shaped melanoma
28:49
has kind of a big
28:49
mushroom shaped head with a kind of a skinnier neck
28:52
and you you can see that the dark area here
28:55
at the base of the tumor
28:56
this area is sort of darker than the apex of the tumor
28:58
which is is typical and classic for uveal melanoma
29:02
so we took this patient to the operating room
29:04
we performed the plaque radiotherapy that we do
29:07
we did the biopsy of his tumor
29:10
and it came back actually
29:11
with amazingly very low risk genetics
29:14
so class 1 prame negative
29:17
and as we just talked about um
29:19
you know those are our markers for low risk
29:21
for metastatic susceptibility
29:23
and on our next generation sequencing testing
29:25
the patient had both a GNA-11 mutation and an EIF1AX
29:29
mutation so what that tells us is that okay
29:31
we've got an initiating mutation GNA-11
29:34
we know that our sampling was of good quality
29:36
from a melanocytic tumor and we know that it's got
29:40
you know low risk changes in its DNA
29:42
so everything in this patient's testing
29:44
points to the concept that his disease is ironically
29:47
not that aggressive
29:48
even though it grew to quite a large size in the eye
29:51
and so here we are nearly five years later
29:53
and this photo on the left
29:54
is actually what his eye looks like now
29:56
now
29:56
we have a full view of his optic nerve and his macula
29:59
his tumor regressed
30:00
from covering the entire center of his um
30:02
fundus to kind of regressing to the infra nasal corner
30:05
here he's alive and well
30:07
his vision actually improved after the treatment
30:10
which um
30:11
is very unusual with the tumor this large um
30:13
and he's doing great
30:14
and feeling very good about his prognosis
30:17
and his long term um
30:19
outlook and I think he actually may even be on the zoom
30:21
feel free to speak up if you'd like
30:23
so this is a situation where in
30:25
so we can kind of illustrate here that
30:27
you know the
30:28
the devil's really in the details of the genetics
30:30
for these patients not so much
30:32
you know in the size of the tumor
30:33
there are real outliers
30:35
if we just had told this patient hey
30:37
you have a huge tumor
30:38
you're definitely gonna die of this disease
30:39
that actually would have been very false information
30:42
and so as I mentioned earlier
30:43
there are outliers on both ends of the spectrum
30:45
there are patients who oh
30:47
there he is he decided to go public
30:49
my patient John Reese
30:50
just commented on the chat that he's here
30:52
so um
30:53
he said now he's famous um
30:55
so the um
30:57
you know I think the
30:58
the important point here
30:59
for patients is that this testing is really critical
31:02
because you know
31:03
the way we practiced in the 80s and the 90s
31:05
and the early 2000s in which we told patients hey
31:07
you know you have a big tumor
31:08
it's gonna be terrible or hey
31:09
you have a tiny tumor you're definitely gonna be fine
31:11
those are really outdated ways of practicing medicine
31:14
these days the idea is that we have
31:16
you know very personalized genetic medicine here
31:18
where every patient's treatment is really
31:21
tailored to them based on the
31:23
the true molecular genetics
31:24
and their own personal tumor
31:26
so this is kind of a nice example of that
31:29
excellent thanks for uh
31:30
sharing that example and we'll go on to uh
31:32
your second case
31:34
alright so this is a 48 year old gentleman who um
31:40
I was just trying to think if
31:41
if this patient is on the chat
31:43
I'm not sure um
31:44
who is a patient of mine who presented with a
31:48
more of a classically medium sized tumor
31:50
which is kind of the size
31:51
that most patients in the United States
31:53
and the developing world present to us in
31:56
his tumor was 15 millimeters in base and 7.9 in height
31:59
kind of I would say
32:00
the upper end of sort of the medium sized category
32:03
um and his genetic testing came back
32:05
after his biopsy and his treatment
32:07
unfortunately with a very aggressive genetics
32:10
class 2 prame positive again with a GNA-11 mutation
32:14
indicating that you know our
32:15
our tumor sampling is from
32:17
you know good quality specimen with a BAP1 mutation
32:20
which also demonstrates that on the DNA level his um
32:23
tumor risk uh
32:25
is quite high um
32:26
and that kind of matches up also with his GEP
32:29
class 2 genotype so in every way
32:31
a very aggressive tumor genetically
32:34
so we said to this patient
32:36
as we do to all of our patients
32:37
with a profile like this okay
32:38
we're really worried about um
32:40
that you you know
32:41
one or two or three of these cells might have escaped
32:43
and gotten out into your
32:44
a systemic circulation before we met you
32:46
so we're gonna survey your liver
32:48
you know quite often and see if something pops up there
32:53
the frequency at which patients like this
32:56
are followed with imaging
32:57
and what imaging you get is quite controversial
33:00
and I think
33:01
kind of too extensive to talk about on this zoom
33:02
but suffice it to say that in our practice
33:05
we follow patients like this with MRI surveillance
33:07
every three to four months
33:09
in the beginning
33:10
and so this patient underwent very close surveillance
33:12
he had a very small metastatic focus
33:14
that was detected early
33:15
he underwent a biopsy of that lesion in his liver
33:18
to confirm that in fact
33:19
it was metastatic uveal melanoma
33:21
and was started very early on Tebentafusp
33:24
which is um
33:24
one of our two FDA approved medications
33:27
for patients with um
33:28
metastatic uveal melanoma
33:29
and he's currently doing well
33:31
on that therapy three year
33:33
almost four years post um
33:34
diagnosis and probably in part
33:36
he's doing well
33:37
because his metastatic disease was picked up so early
33:40
so this case kind of illustrates um
33:43
the other thing that Doctor Williams mentioned
33:44
which is that the other usefulness of this testing
33:47
is so that we can identify those patients
33:49
who are at very high risk
33:50
of developing metastatic disease
33:52
and get them into very close surveillance
33:55
and then after surveillance
33:56
if and when metastatic disease is identified
33:58
get them on treatment
33:59
or get them into clinical trials as soon as possible
34:01
and then we study those patients
34:03
of course over many
34:03
many years as well to see um
34:06
you know what are treatments for metastatic disease
34:08
what kind of effect that has on patients
34:09
and whether it makes a difference
34:11
to start that treatment early
34:12
so particularly for a patient as young as this patient
34:16
you know he's a 48 year old gentleman
34:18
he's quite young he has children
34:19
you know
34:19
we really wanna try to be as aggressive as we can
34:21
in every way
34:22
and one way that we can be aggressive like that
34:25
is to know okay
34:26
this is a patient who we need to survey very frequently
34:30
and very early
34:31
excellent so thanks for those two uh
34:33
wonderful cases I'm gonna share um
34:35
a case here as well
34:36
and I think Doctor Schefler did a fantastic job
34:39
of highlighting uh
34:40
the importance of GEP and prame um
34:42
and my case is going to show a little bit
34:44
about the importance of the DNA mutations
34:47
and next generation sequencing
34:49
so this is a patient that came in
34:53
a woman in her 60s and
34:55
she actually had a huge amount of inflammation
34:57
around the eye and her eye was in pain
35:01
she got orbital imaging and it showed that there was
35:05
a tumor that was partially inside the eye
35:07
and partially outside the eye
35:09
um and she was given steroids on the outside
35:12
that decreased some of the inflammation
35:14
and then she came in to see us
35:16
and when we saw her we could see the lesion here um
35:20
a pigmented lesion consistent with a uveal melanoma
35:23
but she had a very large component outside of the eye
35:26
based on this
35:27
we were planning on doing a enucleation or eye removal
35:30
and we were having a discussion
35:32
about whether or not there would be any benefit
35:34
to doing radiation after this
35:36
the patient wanted uh
35:37
to discuss this with radiation oncology
35:39
and actually when she talked to them
35:41
they weren't sure that this was a melanoma because um
35:44
the lesion had actually shrunk in size
35:47
after she was given steroids
35:49
and so as a result of that
35:50
radiation oncology wasn't uh
35:53
fully on board with us proceeding with enucleation
35:56
because they thought
35:56
if this was a different type of tumor
35:58
they wouldn't want us removing the eye
36:00
unless the diagnosis was correct
36:02
and so you know
36:03
we obviously
36:04
agreed
36:05
that it wouldn't be appropriate to remove the eye
36:07
in the wrong diagnosis um
36:08
and we ended up doing a needle biopsy of this lesion um
36:13
it turns out this lesion had a
36:14
a large amount of necrosis
36:16
basically meaning
36:17
the tumor had outgrown its blood supply a little bit
36:19
and so when we looked at the cells
36:21
the cells were a little bit difficult to assess
36:23
and to confirm the diagnosis
36:25
however we were able to look at the DNA mutations
36:28
and see that there was a GNA-11 mutation
36:31
which is one of the orange mutations
36:32
that we talked about in the beginning um
36:34
showing that this is a melanocytic lesion
36:36
and it also had an SF3B1 mutation
36:39
which is the second uh
36:40
type of mutation that was in teal
36:42
and that helps confirm that this was
36:44
in fact a uveal melanoma
36:46
the patient was then treated with enucleation
36:49
and pathology supported the diagnosis um
36:51
that this was a melanoma and this was a
36:54
a very helpful thing um
36:55
in this scenario because we were able to um
36:58
proceed with the appropriate treatment
37:00
in a timely fashion um
37:02
as opposed to there being some debate
37:04
about what was the correct um
37:06
diagnosis and then
37:07
potentially delaying the appropriate treatment
37:09
and so um
37:10
you know as we kind of mentioned
37:12
looking at DNA sequencing can really help us uh
37:15
confirm number one
37:16
that the tissue that we sampled was the tumor um
37:18
and can help confirm that the tumor was in fact uh
37:21
a melanoma
37:23
and this patient is alive and doing quite well
37:26
and so we have a one last case example uh here as well
37:32
OK great
37:33
um
37:35
alright so this is um
37:37
another patient of mine and this case um
37:41
we're gonna use to illustrate
37:42
the usefulness of next generation sequencing
37:44
which is you know
37:45
the third test that we mentioned
37:47
among the suite of tests that are offered by Castle
37:51
so it's our newest test
37:52
and our test with kind of our least mature data
37:54
but it's turned out um to be very useful as an adjunct
37:58
so this is a um
38:00
older lady in her 80s who I saw
38:03
I think close to a year ago now
38:05
um who presented with a kind of
38:07
a more unusual presentation
38:09
in which she had a kind of salmon coloured lesion here
38:13
underneath her conjunctiva
38:15
oh you guys can't see my mouse
38:16
but this um
38:17
kind of pinkish lesion um
38:19
yeah perfect
38:20
um underneath the conjunctiva
38:21
as well as another lesion at 12 o'clock
38:24
whoever's got the mouse thank you
38:25
Dr. Williams um
38:26
in her uh
38:28
inter chamber so the front of the eye right there
38:30
uh arising from her ciliary body
38:32
and kind of extending into her Iris
38:34
that kind of pinkish whitish area
38:35
that's right and on the ultrasound
38:37
what's called the UBM
38:38
or the ultrasound of the front of the eye
38:39
you can kind of see that tumor
38:41
right there
38:41
it's kind of nudged up against the cornea
38:44
and crowding out the front of the eye
38:46
so
38:46
she had two different lesions that were non contiguous
38:49
not touching each other in the front of the eye
38:50
and particularly that um
38:52
salmon colored lesion on the surface of the eye
38:53
was pretty atypical for this disease
38:55
and so what we did was we did a biopsy
38:57
just as Doctor Williams did in his case um
39:00
more at more from a diagnostic stand point like okay
39:03
what are we dealing with here
39:04
and we found that the tumor had a GNA-Q mutation
39:07
so a initiating mutation as well as a BAP1 mutation
39:11
suggesting that it was a quite an aggressive melanoma
39:14
and actually suggesting that um
39:16
the tumor had actually started
39:18
at that 12 o'clock position
39:19
in the ciliary body and then spread around
39:23
what we call the anterior chamber angle
39:24
and then extended extraocularly out of the eye
39:28
into that space externally
39:29
you can see her GEP came back class 2 and prame positive
39:33
also confirming that she was at her
39:35
very high risk of having um
39:37
metastatic disease
39:38
although her imaging of her liver at that time
39:41
was clean um
39:42
we performed an enucleation um
39:44
and she's still alive and well about a year later
39:47
but this is a situation where
39:48
you know the next generation sequencing
39:50
was really what helped us understand okay
39:52
in fact this is a melanocytic tumor
39:54
this is a uveal melanoma it's not another one of the um
39:57
cancers we might think
39:58
could present in this type of unusual way
40:00
I will add that in our center and
40:02
and for Doctor Williams as well
40:04
and in most centers you know
40:05
who treat a lot of patients with this disease
40:07
we typically do not use these tests
40:09
for diagnostic purposes it's really up to the clinician
40:12
to be able to examine the patient
40:14
and be sure what the diagnosis is
40:16
you know just on the basis of clinical skills
40:17
and diagnostic testing
40:19
but there are these outlier patients
40:20
like this one of mine who
40:22
you know where you really need it
40:24
so it really shouldn't be a situation
40:26
where every single patient is seeing
40:27
the clinician
40:28
is needing this test to prove what the diagnosis is
40:31
but when there are outliers who have unusual findings
40:34
next generation sequencing can be quite useful um
40:37
for that purpose
40:38
so this was kind of a good case to illustrate that
40:40
excellent job this is the last case that we had
40:44
okay so
40:44
this is a 70 year old patient of mine
40:48
who also presented with a kind of medium large um
40:52
tumor that we can see here in his left eye
40:55
on the nasal side so the side closer to the nose
40:58
and it's kind of overhanging the optic nerve
41:00
here's the optic nerve here's the macula
41:02
these are uh
41:03
the blood vessels here
41:05
and then we can see on our ultrasound um
41:07
here's the front of the eye
41:08
here's the back of the eye
41:09
oh sorry
41:10
you guys aren't seeing my mouse
41:11
thank you Basil
41:12
um and then
41:12
you know we can see our tumor there
41:14
that's sort of a very classic looking ultrasound um
41:16
for a uveal melanoma um
41:19
so it's quite a large tumor
41:20
um so this patient underwent treatment with a biopsy
41:24
and his um
41:27
tumor profiling um
41:28
showed you know
41:29
quite high risk genetics he was class 2
41:32
he was prame negative um
41:34
but he was class 2 so certainly a high risk patient
41:36
and he had both a GNA-11 mutation
41:39
so initiating mutation and a BAP1 mutation
41:42
so as a result of the fact that this patient
41:44
had a BAP1 mutation in his tumor
41:46
we thought to ourselves okay
41:48
this is a patient who you know
41:49
has a BAP1 mutation is it possible that he also has
41:53
a hereditary BAP1 mutation
41:55
meaning that he's got this misprint in his DNA
41:57
and all of the cells of his body
41:59
that he and he was born with this mutation
42:01
and that was in fact
42:02
what put him at risk for developing uveal melanoma
42:06
we when we had elicited his family history
42:08
he had actually
42:09
several family members who had had various
42:11
unusual cancers which sort of tipped us off to that
42:14
and so we thought okay
42:15
we need to test this patient
42:16
for a germline BAP1 mutation
42:18
which is a blood test in which um
42:20
a company that we work with in California looks at
42:22
the leukocytes in the patient's um
42:24
bloodstream and says
42:26
the white blood cells and says okay
42:27
does this patient actually
42:28
in fact carry this mutation in all of his cells
42:31
and in fact that test came back positive
42:33
match to the mutation
42:34
that Castle had identified in his tumor
42:36
and that helps us understand okay
42:37
this patient carries what's called BAP1 TPDS
42:40
or tumor predisposition syndrome
42:42
and he was not only at risk for this uveal melanoma
42:44
which we didn't know in advance
42:45
but in fact
42:46
for other unusual cancers as well
42:48
which we now need to screen him for
42:50
and also led to what's called cascade testing
42:52
in which we tested various family members of his
42:55
for this tumor for this syndrome
42:57
and now know that those family members are at risk
43:00
for these other rare cancers
43:02
and screening for those cancers
43:03
can make a major impact on those patients prognosis
43:06
and survival from not only uveal melanoma
43:08
but other tumors so this is a situation where we can uh
43:12
in fact you know
43:13
do quite aggressive preventive medicine
43:16
not only for the patient but
43:17
for his family members as well
43:19
this patient's brother had died in an
43:20
of an unusual tumor called mesothelioma
43:22
which is a cancer of the lining of the lung which um
43:25
is it very heavily associated with this syndrome
43:27
his brother had also had another cancer
43:30
his nephew had also had um
43:32
a cancer at a young age so it was
43:33
you know kind of a widespread family history that
43:36
you know kind of tipped us off
43:38
that we really need to sequence this patient
43:40
for this syndrome we have actually um
43:42
Eve has actually developed a protocol in our center
43:45
in which we actually test all patients
43:47
who have a BAP1 mutation in their tumor
43:49
for the inherited form of this disease
43:51
to make absolutely sure
43:52
that we have not missed a single patient
43:54
and we have a research paper
43:56
that will be published shortly
43:57
kind of talking about these results
43:59
that we've developed in our center
44:00
but irrespective um
44:02
you know the point being here that
44:04
you know
44:04
these mutations will actually sometimes tip us off
44:06
to an even bigger implication of these findings
44:09
not only for the patient but for their family members
44:11
so that's why these tests are very important
44:13
yeah Doctor Schefler
44:14
this is a you know
44:15
a really important case
44:17
and this is something that you presented recently
44:19
I saw your presentation on this
44:20
and I thought it was really powerful
44:21
because a lot of times
44:23
when we're thinking about an inherited BAP1 mutation
44:25
we're thinking about patients who are younger
44:27
or who have a very large family history
44:29
of different types of cancers um
44:31
you know which this patient did
44:33
but I think this is really helpful to understand
44:35
that if a BAP1 mutation is there
44:37
it's worth considering
44:38
at least looking for an inherited BAP1 mutation
44:41
not only for the patient um
44:43
and screening um
44:44
but for family members for
44:45
potentially for children etcetera
44:47
um to be able to assess their risk of both uveal
44:50
melanoma and other cancers moving forward
44:53
so this is a a particularly helpful case example
44:56
awesome thank you so much
44:58
Doctor Williams
44:59
Doctor Schefler
45:00
and Kat uh
45:01
we are so grateful for all of this information
45:04
and I know
45:04
we've had a good number of questions
45:06
coming through the Q&A Kat
45:07
can I have you take the first question
45:09
the one from Amanda essentially
45:10
she says she lives in Costa Rica
45:12
so out of the United States
45:14
and had her eye enucleated
45:15
wasn't offered any genetic testing
45:17
but she was able to get pathology slides
45:19
and the cross sections of the tumor
45:21
preserved in paraffin wax
45:22
is it possible to have any genetic testing done
45:24
from tissue preserved in the wax
45:26
so yes
45:27
all of our tests are validated
45:29
for both fresh tissue and fixed tissue
45:32
if the eye was removed enucleated
45:35
and put in formalin to fix it and then in wax to
45:39
to preserve it and be able to section it
45:41
we can test that the one kind of nuance there
45:43
is that it does need to be from an enucleation
45:46
so we've tried testing other types of fixed issue
45:49
like fixed cells Doctor Schefler knows this
45:52
and it and it just hasn't uh
45:53
worked out because
45:54
there's not enough cell quantity there for us to test
45:58
but if it was an enucleated eye that was fixed
46:00
we can test that so Kat
46:02
address the the kind of subtlety of the question
46:06
I think that this patient asked
46:07
which is a good one which is
46:09
can the center where those slides are present
46:12
do they just send the slides directly to you all
46:15
and then in house
46:16
you're dissecting that tumor off the slides
46:18
yes so the
46:19
the pathologist would need to initiate the order
46:22
and they can either send us the full block of tissue
46:25
and we can section it in house to get what we need
46:28
and send the rest back
46:29
or they can send us slides that are already cut
46:32
it sounds like in this case
46:34
there are already sections cut up and put on slides
46:37
so if they want to send those to us
46:39
they can do it that way
46:41
perfect but we will
46:42
our team would reach out to the pathology lab
46:45
once we receive the order
46:46
to get all of those logistics worked out
46:48
and I feel like Kat
46:49
a good follow up question to this might be
46:51
you know just for anybody who is outside of the country
46:53
is having the DecisionDx-UM test done on um
46:56
an upcoming like
46:57
tumor biopsy for a treatment
46:59
so say they're scheduled for plaque
47:00
they're gonna be treated I don't know
47:02
somewhere in Europe I'm just picking a random location
47:04
but is it possible for them to request the biopsy
47:06
before this treatment even happens
47:08
even if it's just for plaque
47:09
not necessarily an enucleated eye
47:12
we do have the ability to test samples
47:14
from outside of the US we regularly test um
47:18
cases from Canada from Western Canada
47:22
from parts of South America
47:23
we're starting to
47:24
to see more and more samples coming in from
47:26
from places in Latin America
47:27
there are some hurdles that we have to overcome
47:30
with customs so every country has
47:33
you know different regulations
47:34
around sending fresh tissue specimens overseas
47:38
so we that
47:39
those are things that we need to work through
47:41
but yes we
47:42
we are able to
47:43
to test specimens from anywhere in the world
47:46
as long as they can get to our lab
47:47
what I would say kind of as a corollary to that
47:49
is that if you are a patient who is abroad
47:53
outside the US and gonna undergo treatment
47:56
and you haven't worked out those details yet
47:58
the most important thing is to ask the clinician
48:01
to do the biopsy at that time
48:02
cause you can't go back and do it later
48:04
and bank the tissue and I'm sure
48:06
you know
48:06
people can reach out to the folks in the lab at Castle
48:09
and kind of get the information
48:11
about exactly how to store it properly
48:12
and then you know
48:13
while those issues shipping
48:15
customs funding are worked out
48:17
so that at least the tissue is banked
48:19
and being held properly and then could be sent later
48:22
so if the tissue is banked appropriately
48:24
it could be sent a year or two or even more later
48:27
but you have to get it at that time
48:29
so that's kind of the critical decision making
48:31
before the surgery okay wonderful
48:32
so our next question that came in was from Roger
48:36
and he asked about a test that was done in 2012
48:39
and there was a result on the Castle test
48:41
a 1b result and there was no prame listed at the time
48:45
because that test wasn't available
48:47
is it possible to uh
48:49
and there's also no remaining biopsy material
48:51
is it possible to find any prame information
48:53
at this point why or why not
48:55
depending on when the biopsy is done
48:57
there may be some residual tissue material
48:59
in your specific situation
49:01
you noted that there's not any residual material left
49:04
and in that situation unfortunately
49:05
we are not able to obtain additional information
49:09
on prame
49:10
or any of the next generation sequencing tests
49:12
looking at DNA mutations in your situation
49:14
we won't be able to assess that
49:16
if biopsies were done more recently
49:18
um you can uh
49:19
check and see if there are any residual samples
49:21
and sometimes
49:22
those tests can be run if they were not run originally
49:25
um but that's something that needs to be checked
49:26
on a case by case basis
49:28
for anyone who was tested with the GEP
49:30
after mid 2015 or so um
49:34
and if you didn't have prame
49:35
or mutational sequencing done
49:38
at that point in time
49:39
we started storing residual specimen so
49:42
so we may have some residual tissue remaining
49:44
that we could use to run prame and
49:46
and sequencing but it would be
49:48
you know post 2016
49:50
2015 2016 time frame
49:52
the history of that actually is that um
49:57
I had I had some situations in 2015 and 2016
49:59
in which I had patients
50:00
asking exactly the questions that you all are asking
50:02
where they wanted to go back
50:03
and get that type of information
50:04
and I was pretty needy with Castle
50:07
that I wanted to start a program
50:08
where we were able to bank tissue
50:10
exactly for that situation
50:11
and because I anticipated we would have a lot of
50:13
you know new developments over the years
50:15
of other testing that would be useful for patients
50:17
and I wanted to kind of
50:17
prevent that situation to the future
50:19
so one thing I would recommend that you all talk to
50:23
you know friends about
50:24
who are being newly diagnosed with this disease
50:26
is asking the
50:29
the surgeon who's taking care of the patient
50:30
to try to utilize that program the Castle offers
50:32
and bank tissue with each
50:35
with each procedure so that you know
50:36
let's say 10 years from now
50:38
we're not in that situation right
50:39
so every patient has bank tissue
50:40
that can be used down the road
50:42
cause you can't you can't bank it later
50:43
you have to bank it in advance
50:45
so this this may be kind of a no brainer question
50:48
but I guess maybe let's just answer it
50:50
just because I think it's worth answering
50:52
and it comes up
50:53
it comes up a lot every time we talk about the biopsy
50:55
why do you have to have the biopsy done
50:57
before the lesion is treated
50:59
what does that affect
51:01
you know the
51:01
the treatment itself sure um
51:03
I can answer that so basically
51:05
we have studied um
51:07
the COOG group have studied prospectively um
51:10
the biopsy results from before radiation treatment
51:13
we have not prospectively studied
51:15
what the results are after radiation treatment
51:17
and so we do not know if radiation treatment
51:20
is going to affect the results of the biopsy
51:22
and so we cannot stand by the accuracy or validity
51:25
of any information
51:26
that comes out after treatment happens
51:29
um and the
51:29
this is the the reason we want to make sure
51:31
from a quality control perspective
51:33
that the way things have been studied
51:35
and been proven to be accurate
51:37
are the ways um
51:38
that the the test is run for you
51:40
one way to think about what Doctor Williams said
51:42
is that if your surgeon has performed a plaque
51:44
or protons on your eye
51:46
and the whole purpose of that treatment
51:47
is to completely kill all the DNA in those cells
51:51
so that they can no longer grow and get out of the eye
51:53
and that DNA is not of normal quality anymore
51:56
which is exactly what you want
51:57
and therefore you cannot assess its level of expression
52:00
of different genes it's dead
52:02
so that's kind of the way for patients
52:04
that I always explain that to patients
52:05
you know we don't actually want that DNA to be active
52:07
and expressing the genes it did before it was treated
52:10
right so it's now crappy tissue
52:12
it's basically a big fat scar
52:14
and we're not gonna go back in there
52:15
and try to understand it's biology anymore
52:17
cause it's not active the way it was prior to treatment
52:20
okay
52:20
so this next question is talking about Iso-disomy 3
52:24
is that a test uh
52:25
marker that is equivalent to the BAP1 and the class 2
52:28
so maybe just for some background
52:30
you know I mentioned
52:31
I think when I was talking about cytogenetics
52:34
cytogenetics is the study of
52:35
kind of looking at an array of chromosomes
52:37
so you know what
52:38
we all have
52:39
a certain number of chromosomes that we're born with
52:41
and there are actually ways to kind of
52:43
take those chromosomes and sort of lay them out
52:45
almost on like
52:46
a visual diagram and see them
52:48
and sometimes some patients
52:49
either from inborn errors
52:52
or from things that happen later in life
52:53
will actually be missing a piece of a chromosome
52:55
of a particular chromosome
52:57
a part of it or even a whole chromosome or
52:59
or chromosomes can be duplicated and so forth
53:01
so it was it was discovered in the early 1990s
53:04
that chromosome 3 was really important in this disease
53:07
and essentially
53:08
that if there were two healthy copies of chromosome 3
53:11
that implied that a patient would have a lower risk
53:13
in the tumor cells from the
53:15
from the uveal tumor
53:16
that if there were two healthy copies of chromosome 3
53:18
that it was less likely
53:19
that a patient would develop metastatic disease later
53:21
but if there was one copy
53:23
or monosomy three
53:24
that it was more likely that the tumor was aggressive
53:28
and the patient was likely to develop
53:30
metastatic disease
53:30
so Iso-disomy is an unusual situation where
53:33
if you just kind of
53:34
look superficially at the chromosomes
53:36
it looks like there are two healthy copies
53:37
but in fact
53:38
what's happened is that one copy has been lost
53:40
and the remaining copy has sort of reduplicated itself
53:44
and so
53:44
it kind of looks superficially like they're two copies
53:46
but really there's only one healthy copy
53:48
and so you know
53:49
it stands to reason to make sense right
53:51
that that's a riskier situation than normal
53:53
healthy disomy and a higher risk feature
53:57
in general cytogenetics are not as predictive as um
54:01
molecular testing that
54:03
of the kind that we've been talking about today
54:05
and so it's hard to sort of say okay
54:08
how risky is that compared to the GEP
54:10
class or the next you know
54:12
findings on next generation sequencing
54:13
but it certainly is kind of a high risk feature
54:15
so what I wrote in the chat to this patient is that
54:18
you know
54:18
I would recommend that a patient who came to me
54:20
was treated elsewhere
54:21
and had that testing have more frequent surveillance
54:23
than a patient who had disomy 3 certainly
54:27
but it's not it's really
54:28
you know not quite as accurate
54:29
as what Doctor Williams and I work with every day
54:31
so our next question is from Elisa
54:33
and this says
54:33
what are the updates on the 1A versus the 1B
54:36
in regards to risk so
54:38
the class 1a and 1b groups were developed
54:43
based on the very first prospective validation
54:46
of the GEP test
54:47
that was the COOG1 study and based on that cohort
54:52
it looked like class 1a and class 1b stratified
54:56
separated with class 1a being low risk
54:58
class 1b intermediate risk
55:00
what's interesting is the COOG2 study
55:02
which is more recent much larger
55:04
three times larger than COOG1
55:06
did not find significant risk stratification
55:10
between 1a and 1b at least not at the five year mark
55:13
and I think one potential reason for that
55:15
is that COOG2 contain and
55:17
I'd love to hear Doctor Schefler and Doctor Williams
55:19
thoughts on this too
55:19
but
55:20
COOG2 contained many more small tumors than COOG1 did
55:23
so it's a different um
55:26
demographic of patients
55:28
and there may be something about subclass
55:31
the 1a and 1b groups
55:32
that is more important for the larger tumors
55:35
so Castle is
55:36
is continuing to report the subclass information on
55:39
on the test report and um
55:42
my understanding is
55:43
COOG will continue to follow those groups over time
55:46
to see if there's any long term value for 1a and 1b
55:49
so I guess my initial confusion around the 1a
55:52
1b was with the new reporting
55:55
was that um
55:56
it seemed like the prame was a little more important
55:58
than the differentiation between the 1a
56:00
1b can you guys explain why that is
56:03
Kat I love
56:03
I love that you said that you're still expanding on
56:05
on following these patients
56:07
to make sure that you're seeing
56:08
what happens in the future
56:09
yeah I think that's a fantastic question
56:11
and I think you know Kat
56:12
you did a really good job at
56:13
at highlighting this
56:14
and so I think initially we were thinking
56:17
based on what we saw from COOG1
56:19
that 1a and 1b really stratified and really separated
56:22
in terms of prognosis
56:23
where 1b had a higher risk than 1a
56:27
what we realize now with COOG2 is that there really is not
56:31
um as much of a difference between 1b and 1a
56:33
and so we kind of look at class 1 as a group together
56:36
overall the COOG group will continue to evaluate that
56:39
down the road to
56:40
to make sure that's the case
56:41
but with a much larger sample
56:43
it looks like class 1 kind of stratifies together
56:46
in regards to your question about prame
56:49
prame was something that we thought made a difference
56:52
uh early on
56:52
and Doctor Schefler kind of mentioned uh
56:54
the paper in I think 2016 or 2017
56:57
that kind of highlighted the role
56:58
and the significance
56:59
of prame in molecular prognostication
57:02
in terms of the risk of metastasis
57:04
what COOG2 did was evaluate that prospectively
57:07
to actually assess how much of a difference prame made
57:10
and so basically we understand that the first
57:13
most important thing is GEP
57:15
looking at class 1 versus class 2
57:17
and then once you get that information
57:20
prame additionally stratifies
57:22
so provides additional information
57:24
on top of class 1 and class 2
57:26
to assess risk and so at this point
57:28
GEP class 1 and class 2 followed by prame
57:31
negative and positive
57:32
seems to be the best way to classify these lesions
57:35
as opposed to focusing on 1a versus 1b
57:38
and and I do think that
57:40
you know initially as
57:42
as in and Doctor Schefler
57:43
you can uh
57:44
correct me if I'm wrong
57:45
cause you were involved in this at
57:46
at a much earlier point um
57:48
than I was but I think
57:49
you know
57:49
when you're trying to involve patients in studies
57:51
and you're doing biopsies
57:52
you're using tumors of size
57:54
that you can feel more comfortable
57:55
getting enough tissue and um
57:57
we were doing biopsies on larger tumors
57:59
and by the time COOG2 came around
58:01
we were including patients with smaller tumors
58:03
feeling more comfortable doing biopsies
58:04
of those lesions
58:05
and with the excellent results that we showed earlier
58:08
we know that there's a really
58:09
really high rate of getting sufficient sample
58:12
and so as a result
58:13
in the COOG2 a much larger range of tumors were um
58:18
included in the study and
58:19
I think that's much more representative
58:21
of what we're seeing in a daily basis um
58:23
with our patients having a range of both smaller tumors
58:26
and larger tumors and kind of everything in between
58:29
yeah I agree with that
58:30
that's absolutely true the reason why the kind of
58:33
range of sizes of tumors in COOG2 was larger than was
58:36
was kind of had a larger range
58:38
and went down to much smaller tumors than COOG1
58:39
was just because
58:41
most of the clinicians involved in this work
58:43
you know at that point
58:44
had many more thousands of patients under their belt
58:47
and were more comfortable
58:48
surgically biopsying smaller tumors
58:49
which are technically more challenging
58:51
I would add to that um
58:52
this is getting pretty nuanced that
58:54
and this is related to one of the questions in the chat
58:56
that what we've learned over time
58:58
in large part because of this work
58:59
is that when tumors are very large
59:01
one of the things that indicates us is that they've
59:04
generally that they've been there a long time
59:06
and they've had a lot of time to grow and mature
59:09
and for the misprints in their DNA to be propagated
59:13
right so
59:13
what we understand better now is that
59:15
with really large tumors typically
59:16
the genetics throughout the tumor
59:18
tend to be pretty homogeneous
59:19
most of the
59:20
of the cells kind of carry the same mutation
59:22
and express them in the same way
59:24
what we understand better now is that with really
59:26
really little tumors which are
59:27
you can think of them as
59:28
like earlier in the evolutionary biology
59:30
the disease there's a little bit more heterogeneous
59:32
there's also can be a situation where we have
59:34
what are called competing clones
59:36
like one little clone that essentially is like class 2
59:38
and one little clone less class 1
59:39
and they're competing
59:40
and the more aggressive clone will typically win out
59:43
in many ways part of what the study did for us
59:46
which has been so groundbreaking
59:48
is to help us understand what's happening
59:49
in the very beginning of the biology
59:51
cause that's really
59:52
how we're gonna learn
59:53
to solve the mystery of this disease
59:56
and a lot of our understanding of the biology
59:58
in those early tumors
59:59
with competing clones and heterogeneity
1:00:01
and all the complexity is really still
1:00:02
like evolving day by day
1:00:04
many of the I think
1:00:05
confusing results we get
1:00:06
are in that setting of small tumors
1:00:08
and it's important to kind of
1:00:09
talk to your doctor about those subtleties
1:00:13
um if you have a result that has
1:00:16
what feels like conflicting information between the GEP
1:00:19
the prame and the NGS
1:00:20
there are cases where those things don't all line up
1:00:22
and there are reasons for that
1:00:24
that are often
1:00:26
very much at the forefront
1:00:27
of what we're understanding about this disease
1:00:29
and so you know
1:00:30
hopefully
1:00:30
each person's clinician can help them understand that
1:00:32
can we just generally reiterate
1:00:35
what's changed you know
1:00:36
as of 2025 NCCN guidelines for surveillance
1:00:40
what's changed because of the new reports
1:00:42
and how should somebody who's particularly further out
1:00:45
like say 5
1:00:46
10 years out
1:00:47
how should they be advocating with their care for how
1:00:51
you know their scans are happening
1:00:53
or their surveillance is taking place
1:00:54
this is a very interesting question
1:00:56
and this is something that we are still discussing uh
1:00:58
quite commonly as a community of ocular oncologist
1:01:01
and medical oncologist as well
1:01:03
uh we kind of understand
1:01:04
that there's a bimodal distribution
1:01:07
to the way metastasis develops
1:01:08
basically meaning there's a group of patients
1:01:10
that are at risk for metastasis
1:01:12
early on after diagnosis
1:01:14
within the first few years
1:01:15
and then there's a group of patients
1:01:17
that may develop metastasis later on
1:01:19
so after five years or so
1:01:21
um and we do have some understanding of which patients
1:01:24
those are from COOG1
1:01:26
but we are gaining more understanding from that with COOG2
1:01:29
as we know that COOG2 is more recent
1:01:31
we have not had these patients get out far enough
1:01:34
to fully understand this information yet
1:01:36
and so
1:01:37
I think this is a little bit of a personal decision
1:01:39
between the patient the ocular oncologist
1:01:41
the medical oncologist in terms of how
1:01:43
how long they follow uh
1:01:45
systemic surveillance I actually uh
1:01:47
in our practice
1:01:48
we do something similar to Doctor Schefler's practice
1:01:51
where we do um
1:01:52
surveillance up to 10 years
1:01:54
and then kind of have a little bit more of a nuance
1:01:57
conversation after that
1:01:58
um but I think it is a uh
1:02:01
it's not something that we understand fully
1:02:03
in order to be able to say
1:02:04
there's definitive information
1:02:06
as we get further away from the COOG2
1:02:08
we will have longer follow up
1:02:10
and we'll have more data
1:02:11
to really support that decision
1:02:13
over time with the current data
1:02:15
do medical oncologist and I'm
1:02:17
I'm making the assumption that
1:02:19
you know as ocular oncologist
1:02:20
you guys are mostly sending your patients out
1:02:22
for surveillance to a medical oncologist
1:02:25
especially in like
1:02:26
the case of a higher risk patient
1:02:27
but obviously like
1:02:28
you guys know how the surveillance works as well
1:02:30
I know there's there's kind of a mix right
1:02:32
of patients
1:02:32
who have been referred to a medical oncologist
1:02:35
who specializes in uveal melanoma
1:02:37
and then there's also groups of patients
1:02:39
who just don't have access to a doctor like that
1:02:41
and so they continue to be monitored
1:02:43
and scanned by their ocular oncologist
1:02:46
is there anything like
1:02:47
right now that patients you know
1:02:48
who are recently diagnosed
1:02:50
or coming up on diagnosis
1:02:52
maybe they're seeing this
1:02:52
you know five months after they got diagnosed
1:02:54
that they should keep in mind from those test results
1:02:57
just to make sure that they're getting scanned
1:02:59
as frequently as they need to be
1:03:00
a specific example would be
1:03:02
like in the case of a class 2 prame negative patient
1:03:05
you know what's the nuance there
1:03:06
should they still be seen at the
1:03:08
at the super class 2 you know
1:03:10
every three to four months
1:03:11
or does the prame negative make it six months is more
1:03:14
okay like
1:03:15
how do you guys make the decisions for how to
1:03:17
how to monitor surveillance that way
1:03:19
I think um
1:03:19
Kat did a fantastic job in her session
1:03:22
talking about the the national guidelines
1:03:24
the NCCN guidelines and um
1:03:27
those are something that are
1:03:28
that are helpful standards that we use
1:03:30
from an imaging standpoint where um
1:03:32
patients with a class 1 prame negative lesion
1:03:35
we recommend following on a once a year basis
1:03:38
or somewhere around once a year
1:03:40
um class 1 prame positive
1:03:42
we look between six to 12 months depending
1:03:44
and then class 2
1:03:45
whether or not it's prame negative or positive
1:03:47
are considered high risk and so those uh
1:03:50
patients
1:03:50
we usually follow every three to four months or so
1:03:53
this is something that we are still trying to fine
1:03:55
tune as a community as well
1:03:57
and there was a recent Delphi study
1:04:00
basically a study um
1:04:02
composed of a number of ocular oncologist
1:04:04
medical oncologist um
1:04:06
radiologist as well and others
1:04:08
kind of looking at what practice patterns are
1:04:11
not only for how often testing should be done
1:04:13
but also for what type of imaging should be used
1:04:16
and so this is something that has been submitted
1:04:19
and hopefully we'll be published soon
1:04:20
and so people will be able to get access to
1:04:22
the information about what we agree upon as a group
1:04:25
but there are some nuances in this
1:04:27
that we are still trying to figure out
1:04:29
I would say in addition to that
1:04:31
that the Delphi study concept that Dr.
1:04:33
Williams talking about
1:04:33
was basically just like a bunch of people in a room
1:04:35
expressing their opinions
1:04:36
and the reason why Delphi studies are done
1:04:37
is when there's not good high quality scientific data
1:04:41
that the answer is really
1:04:42
we don't know there are no prospective clinical trials
1:04:45
looking at different screening strategies and
1:04:48
and which lead to earlier diagnosis of metastatic disease
1:04:51
and then if you have an earlier diagnosis
1:04:53
does that actually lead to longer term survival
1:04:55
believe it or not
1:04:55
we actually don't know the answer to that
1:04:57
so every center does the the long and short is
1:04:58
every study center does it differently
1:05:00
it's sort of based on clinical experience and opinion
1:05:03
um I think it's hard to sort of
1:05:05
point fingers at anyone saying hey
1:05:06
you should be doing it this way or that way
1:05:07
because we really don't have standards
1:05:10
so we each have our own sort of algorithm
1:05:12
a lot of it is based sadly um
1:05:15
as many things are in American medicine
1:05:16
on what insurance you have
1:05:17
what they'll cover what you have access to
1:05:20
and so
1:05:20
there's a range of strategies that are acceptable
1:05:24
and unfortunately there really is that
1:05:27
there's not a gold standard and
1:05:28
and I think the thing worth understanding
1:05:30
as a patient also is that
1:05:32
the reason
1:05:33
why it's hard for us to do prospective trials on this
1:05:35
is that these clinical trials cost a lot of money
1:05:37
doing high quality
1:05:39
clinical trials is extraordinarily expensive
1:05:41
and if you think about it
1:05:42
for most of these types of studies
1:05:43
you need a funding agency
1:05:44
who has an interest in the outcome
1:05:46
right so if we're doing screening right
1:05:48
primarily we're using cat scans and MRI scans right
1:05:50
those companies are not gonna pay for this
1:05:52
they don't really particularly care what happens
1:05:54
and you know
1:05:55
in the past we got a lot of funding for this from
1:05:58
for studies like this from NIH
1:05:59
a lot of that funding you know
1:06:01
has gone away and um
1:06:03
so it's just logistically and financially
1:06:05
a very very hard thing for our community to make happen
1:06:09
and get funded
1:06:10
but that doesn't mean we don't think it's important
1:06:12
and we don't wish we could
1:06:13
we just it's very difficult to make it happen
1:06:17
in a really rare cancer
1:06:19
we have kind of a unique question here
1:06:21
the risk class is determining
1:06:25
like class 1
1:06:26
class 2 that determines the risk of metastasis
1:06:29
and so if you're say
1:06:30
your class 1 and you end up metastasizing
1:06:33
you know that does
1:06:33
does that information the prame negative
1:06:35
prame positive does that stay important
1:06:38
in treating your metastatic disease
1:06:40
so as we've all been discussing this morning
1:06:43
what GEP and prame have been studied
1:06:45
for is their ability to predict the likelihood
1:06:47
that a patient will develop metastatic disease
1:06:49
they have not been studied for this more nuanced
1:06:52
complicated question which is okay
1:06:54
how aggressive will the metastatic disease be
1:06:56
once it develops
1:06:57
we just don't have that data and don't know
1:06:59
certainly it seems logical right
1:07:01
it stands to reason that
1:07:02
if the disease is more aggressive
1:07:03
the eye may be more aggressive
1:07:05
once it spreads throughout the body
1:07:06
but the truth is
1:07:07
once a cancer is sort of swimming around the whole body
1:07:10
there are many many factors that affect how it acts
1:07:14
how young is the patient
1:07:15
how strong is their immune system
1:07:16
you know all sorts of crazy details
1:07:18
are related to the liver angioanatomy
1:07:19
the blood vessels in the liver
1:07:20
it's just extremely extremely complicated
1:07:22
and so this testing in the eye is not used
1:07:24
and not validated
1:07:25
to predict rates of metastatic disease
1:07:28
wants it to develop so I wouldn't
1:07:30
I wouldn't use it to extrapolate it
1:07:31
to gain that type of information
1:07:33
agree this is kind of just a historical question
1:07:36
do you guys have any studies that are happening
1:07:39
any questions that we're trying to answer
1:07:40
as far as um
1:07:42
is it possible to make a guess
1:07:43
as to how long ago
1:07:44
a primary and secondary tumor mutation begins
1:07:47
as an example I guess I'll use myself
1:07:49
class 2 prame positive
1:07:51
how likely is it that that's been going on for
1:07:54
two years three years
1:07:55
five years before it was ever diagnosed
1:07:56
in my eye yeah
1:07:58
I think this is another question
1:07:59
that we don't know the answer to
1:08:01
and I think it is very difficult for us to assess
1:08:03
this is uh
1:08:04
something that each patient is going to be
1:08:06
a little bit different and when we look at the tumors
1:08:08
um we have seen very
1:08:09
very small tumors that are class 2 prame positive
1:08:12
we've seen very
1:08:12
very large tumors that are class 1 prame negative
1:08:15
you know Doctor Schefler showed an example like that
1:08:17
and so um
1:08:19
you know previously
1:08:20
years ago we would have thought that the very
1:08:21
very large tumors
1:08:22
were the ones that were more aggressive
1:08:24
potentially with more metastatic potential
1:08:27
maybe because we were thinking
1:08:28
they were growing at a faster rate
1:08:29
and were able to achieve a larger size as a result
1:08:33
but as we've done more biopsies
1:08:34
on tumors of different sizes
1:08:35
and understood their molecular profiles
1:08:38
a little bit more
1:08:38
we see that there's a huge range in those
1:08:40
and so
1:08:41
it is really difficult for us to make that assessment
1:08:43
at the moment this question uh
1:08:45
is asking when you do a biopsy at the time of treating
1:08:48
say a large tumor
1:08:49
is it possible for the biopsy
1:08:50
to test different areas of the tumor so
1:08:53
you know the ball
1:08:54
and then
1:08:54
can we take a sample from here and a sample from here
1:08:56
why or why not would that be a good idea
1:08:58
when these tests were originally developed
1:09:00
tumor heterogeneity
1:09:01
or the idea that the genetics were the
1:09:03
some of the key genes
1:09:05
involved in the development of the tumor
1:09:07
and which of those were mutated
1:09:08
and then how they were being expressed
1:09:10
was gonna be variable in different parts of the tumor
1:09:11
was very like
1:09:13
a very hot topic like
1:09:14
well what if you sampled one part of the tumor
1:09:15
and you get one answer but if you had sampled another
1:09:17
it would have been another answer
1:09:19
it's become clear over time
1:09:21
that the bigger and larger
1:09:22
and more mature the tumor is
1:09:23
the more homogeneous the expression of the genes is
1:09:25
and again as I said before
1:09:26
that kind of makes sense right
1:09:27
it's been longer it's been there
1:09:29
in theory longer growing more
1:09:31
and sort of had more time for all the cells to sort of
1:09:34
resemble each other in very small
1:09:35
early tumors there is a little bit more heterogeneity
1:09:38
but by and large the better and better we've gotten
1:09:41
technically and surgically during these biopsies
1:09:43
the more and more we're getting good
1:09:45
at being able to extract very valuable information
1:09:48
even from very small tumors
1:09:50
you know
1:09:50
and kind of reliable data even from small tumors
1:09:53
all that being said
1:09:53
it is technically possible to do more than one biopsy
1:09:56
from different spots in a tumor at the time
1:09:58
and there are certainly situations
1:09:59
where clinicians will do that
1:10:00
so for example
1:10:01
if there's a tumor
1:10:02
where one part of it looks very necrotic
1:10:03
meaning like it's almost cut off its own blood supply
1:10:05
it's very dead but another part that looks very active
1:10:08
sometimes the clinician will say hey
1:10:09
I'm gonna
1:10:10
I'm gonna take tissue from that more active part
1:10:12
cause it's more likely to be more representative
1:10:14
of what's going on now
1:10:15
that kind of thing but routinely
1:10:17
I would say
1:10:17
most ocular oncologists who do these tests will pick one spot
1:10:21
and send that off
1:10:23
and just assess the answer from that one spot
1:10:27
as Kat mentioned we do really
1:10:28
three
1:10:29
sort of sets of tests these days on most patients
1:10:31
and all of those sets can be done from that one spot
1:10:34
personally in our center
1:10:35
because we bank tissue from every patient
1:10:37
as I mentioned we actually always do two spots
1:10:39
but it isn't exactly for the purpose of
1:10:41
of the heterogeneity problem
1:10:42
it's because we want
1:10:44
we want tissue for those two purposes
1:10:46
so so it's kind of a complicated question but
1:10:48
but the answer is certainly
1:10:49
technically that can be done
1:10:50
and in certain situations
1:10:51
it's clinically appropriate
1:10:52
thank you Doctor Schefler
1:10:54
um okay
1:10:54
so this is talking about BAP1 mutation
1:10:57
we've talked a lot about these different
1:10:58
genetic mutations and the sequencing test
1:11:01
or the sequencing section of the DecisionDx-UM
1:11:04
test is it possible
1:11:06
to learn more about the specific BAP1 mutation
1:11:09
that a patient has and if so
1:11:11
how do they get that information
1:11:12
you know I
1:11:13
I think in in particular in relation to this question
1:11:15
once you have a BAP1 mutation
1:11:17
we know that increases the risk
1:11:18
um and then looking at gene expression profile
1:11:22
or prame is gonna give us
1:11:23
kind of the most important information
1:11:25
there's a lot that we're still learning
1:11:27
about BAP1 mutations
1:11:29
we're learning which ones are pathogenic
1:11:31
and which ones aren't which ones um
1:11:33
kind of play a more significant role
1:11:34
and which ones don't and that's some
1:11:36
and
1:11:36
we're also learning that there are some BAP1 mutations
1:11:39
that might be harder for us to identify
1:11:41
and so I think this is a
1:11:43
an area where we still have a lot more to learn
1:11:46
but I think once we know we have a BAP1 mutation
1:11:49
there is an increased risk
1:11:50
and so uh
1:11:52
kind of from that you can think about well
1:11:54
going back to GEP
1:11:55
and prame to really understand your risk profile
1:11:58
and then kind of looking forward uh
1:12:00
thinking about hereditary disease etcetera
1:12:03
I think
1:12:04
the Castle test itself does come with information
1:12:07
about the specific type of BAP1 mutation
1:12:09
that's there if you want that information
1:12:11
um so it is available
1:12:13
but we're not 100% sure what to do with that yet
1:12:16
the question says what percent of tumors with BAP1
1:12:19
will show a germline BAP1 mutation
1:12:21
so it's a great question across the world
1:12:24
the thing about these inherited family cancer syndromes
1:12:26
is that they run in families
1:12:28
and they run in populations actually
1:12:30
so first off I would say that they
1:12:32
it probably varies by region around the world
1:12:34
because what we think happens with these syndromes
1:12:36
is that
1:12:36
there's probably something called a founder mutation
1:12:38
which is literally that like
1:12:39
five or six
1:12:40
or 10 or 15 generations ago in human history
1:12:42
literally someone had this mutation
1:12:44
and then
1:12:44
it kind of spread throughout a particular population
1:12:46
so may vary around the world
1:12:48
that being said
1:12:49
the current literature in the United States
1:12:50
reflects about a 1 to 3% incidence of this
1:12:54
among patients with uveal melanoma
1:12:56
first of all this is already a rare disease right
1:12:58
so we're talking about a very
1:12:58
very rare small population
1:13:00
within an already rare group of patients
1:13:02
in our center because
1:13:03
we've been doing studies over the last couple of years
1:13:06
looking at this we actually are seeing that percentage
1:13:08
be a little higher more like in the 8 to 9% risk
1:13:11
but either way it's very low
1:13:12
and so the majority of patients who walk in the door
1:13:15
and see us and have uveal melanoma
1:13:16
and even if you have a BAP1 mutation
1:13:18
your tumor will not carry this syndrome
1:13:20
but we have broadened in our center
1:13:22
the people in whom we test for the germline syndrome
1:13:24
because it has such profound implications for that
1:13:27
both that patient and their family members
1:13:28
as I mentioned before and it's also worth knowing
1:13:31
that there's at least one other inherited syndrome
1:13:33
that has been identified that increases
1:13:35
patient's risk of developing uveal melanoma
1:13:37
and there are likely to be others
1:13:39
part of the problem with this
1:13:40
is that science is always evolving
1:13:41
and we're always discovering more
1:13:42
so fifteen years ago
1:13:44
we didn't even know about the BAP1
1:13:45
tumor predisposition syndrome right
1:13:47
and now we know about this one and at least one other
1:13:49
and there are going to be others
1:13:51
so I take care of a um
1:13:53
a number of families who clearly have a
1:13:56
an inherited family syndrome
1:13:57
in which many people in the pedigree
1:13:58
have different cancers
1:13:59
but they come up negative on the BAP1 germline test
1:14:02
and that suggests there's something else
1:14:04
that has not yet been is not
1:14:06
is just not yet understood
1:14:07
and that that's also true across all of cancer medicine
1:14:10
for example there
1:14:11
to use a kind of a more common example
1:14:12
you know breast cancer is very
1:14:14
very common in the US population and around the world
1:14:17
and most patients um
1:14:20
you know test negative for BRCA
1:14:22
and these other inherited family cancer syndromes
1:14:24
but
1:14:24
there are a good number of families across the world
1:14:27
where like
1:14:28
every woman in the pedigree has breast cancer
1:14:31
but they come up negative on those tests
1:14:32
and that suggests there are just other syndromes
1:14:34
that have not yet been identified
1:14:35
so we don't understand all this
1:14:37
and that's important to know
1:14:38
yeah I think
1:14:39
you know
1:14:40
doctor Schefler's answer is really important
1:14:42
um number one
1:14:43
I kind of mentioned this when she shared her case
1:14:45
um some of the work that she's done at her center
1:14:48
is helping us
1:14:48
kind of understand this a little bit more
1:14:50
and I think will help shape
1:14:51
a little bit about how we think about this
1:14:53
moving forward
1:14:54
and I think a lot of the answers to these questions
1:14:56
that we've um
1:14:57
been kind of given lately has shown how
1:15:00
how much we know and how far we've come
1:15:03
but also that there's still a lot more um
1:15:06
for us to learn and so um
1:15:08
you know continue asking these questions
1:15:10
because that helps push and drive the science um
1:15:13
and we will continue to try and do as much as we can to
1:15:16
to learn more as a as a community in general
1:15:19
um but we definitely still have a long way to go in
1:15:21
in terms of understanding all of these things
1:15:24
really good point
1:15:24
one additional thing that Doctor Williams is saying
1:15:27
that just made me think of something
1:15:28
that I think is worth adding on
1:15:30
one of Kat's slides
1:15:31
or maybe it's Doctor Williams slides
1:15:33
you know it mentioned like
1:15:35
the sensitivity and the accuracy of the castle test
1:15:37
and the likelihood that you might get like
1:15:40
a negative result and that likelihood is very
1:15:42
very low as his slide showed
1:15:44
it's kind of in the like 1 to 2% range
1:15:45
but I'm sure that everyone on the zoom has had
1:15:48
you know
1:15:48
friends they've made in the uveal melanoma community
1:15:50
like on social media
1:15:51
who were told that their tumor was class 1
1:15:53
prame negative
1:15:54
and then ended up developing metastatic disease anyway
1:15:57
so a couple of points I think
1:15:59
that are important to make about this
1:16:00
one is that you know
1:16:00
no medical test is 100% accurate
1:16:03
science and the human body
1:16:04
are just too complicated
1:16:05
for us to be perfect all the time
1:16:07
at everything and the other thing is
1:16:08
that
1:16:09
there's a lot of real complexities with this testing
1:16:11
the Castle tests were designed to assess
1:16:13
as we've been saying
1:16:14
the prognostic implications of these mutations
1:16:17
meaning like
1:16:18
once you have uveal melanoma
1:16:19
what's the chance
1:16:20
that one or two of those cells got out
1:16:21
and are hiding in your liver
1:16:22
they're not designed to assess
1:16:24
the surgical skills of the surgeon
1:16:27
so if the surgeon sends a piece of retina
1:16:30
to the lab in Arizona
1:16:31
the algorithm is actually designed
1:16:34
to come back class 1 prame negative
1:16:35
and the reason is
1:16:36
that the retina does not express those genes that
1:16:39
when mutated you know
1:16:40
are overexpressed or under expressed
1:16:41
in this tumor it's like
1:16:43
nor we think of it as healthy
1:16:44
normal tissue so it doesn't express those things
1:16:45
so that's how it comes back
1:16:47
and so everything comes back
1:16:49
to the surgical skills of the clinician
1:16:51
and whether the biopsy was done technically
1:16:53
in an appropriate and accurate way
1:16:55
some of these tumors particularly the small ones
1:16:57
the the technical skills required to do them are
1:16:59
are quite complex
1:17:00
and require a zillion years of training
1:17:02
just like Doctor Williams and I did it
1:17:04
but even after a zillion years of training
1:17:07
you know there are cases that are challenging
1:17:09
some tumors bleed some um
1:17:11
some eyes uh
1:17:13
some tumors are more um
1:17:14
sticky and
1:17:15
they really just don't want to be released
1:17:17
from their micro environment
1:17:18
and go into the instrument that we use to get them
1:17:21
and also scarily enough
1:17:23
we actually don't have the ideal instruments
1:17:25
developed for these procedures yet
1:17:26
we were doing the best we can
1:17:28
with the instruments that have been developed
1:17:29
and our micro instruments are quite good
1:17:30
but they're not perfect yet again
1:17:33
we are victims of the fact that this is a rare disease
1:17:36
and surgical device manufacturers
1:17:38
are not interested in helping us
1:17:39
with a disease
1:17:40
that only affects 2,000 patients per year
1:17:42
so there are a lot of nuances and complexities
1:17:44
and if you meet a patient online who says
1:17:46
well
1:17:46
I was class 1 prame negative and I got metastatic disease
1:17:49
the test is useless that's really not true
1:17:51
and there's just a lot of nuances to it
1:17:54
so yeah absolutely
1:17:56
just wanted to put that out there
1:17:57
and those fears come up a lot for patients
1:17:58
and I'm sure you guys see that
1:17:59
totally understandably totally understandably
1:18:01
I don't feel like we need to go into
1:18:02
some of these fears um
1:18:03
we have addressed some of these in previous podcasts
1:18:05
and previous discussions with Doctor Schefler
1:18:07
and also with Doctor Williams where um
1:18:09
if you want to check those out on the YouTube channel
1:18:11
or on the Eye Believe Podcast
1:18:13
we do talk about like
1:18:14
the why or why not for a biopsy
1:18:15
we talk about kind of the risk
1:18:17
cost benefit all of those different things
1:18:19
overall though
1:18:20
the information that we're sharing here with COOG2
1:18:22
and with the update kind of to what we know is
1:18:25
like Doctor Williams said
1:18:26
you know this is
1:18:27
this is so much more than we knew 5
1:18:29
10 years ago and we have so much more to learn
1:18:32
but we've made some really huge strides
1:18:34
I do want to like
1:18:35
just kind of point us in the direction of the future
1:18:37
so one of the things you guys mentioned
1:18:39
throughout the presentation
1:18:40
was that the information you know
1:18:42
gleaned from the biopsy can tell a patient
1:18:45
if they are potentially eligible
1:18:46
for an adjuvant clinical trial
1:18:48
are there any current adjuvant clinical trials
1:18:50
based on the new information that we have
1:18:51
and just in the the present day
1:18:53
as of um
1:18:54
as of today I suppose uh
1:18:56
there are some adjuvant clinical trials I know um
1:18:59
at our center in university of Miami through uh
1:19:02
the work of Jose Lutzky a medical oncologist
1:19:04
and Bill Harbour
1:19:06
kind of uh
1:19:07
help start uh
1:19:08
or who started COOG as Doctor Schefler mentioned uh
1:19:11
they came up uh
1:19:12
with a trial looking at quisinostat
1:19:14
which is basically an HDAC inhibitor
1:19:16
and so um
1:19:17
basically meaning that it is currently enrolling
1:19:19
for patients who have high risk disease
1:19:22
so patients with class 2 disease
1:19:24
are potentially eligible
1:19:25
to enroll in that clinical trial
1:19:27
so that's at least one trial that's available
1:19:30
and is currently enrolling in our center
1:19:33
I would say like
1:19:33
at any given time mostly over the last decade
1:19:36
there've been
1:19:36
anywhere between two and four adjuvant trials
1:19:38
open across the United States
1:19:39
and then they've come they've opened
1:19:41
they've enrolled and sadly
1:19:42
they've all turned out to have negative results
1:19:45
which is why we don't have FDA approved therapy
1:19:47
to use in the adjuvant setting
1:19:48
but if you live in a city
1:19:51
where there's an adjuvant trial available
1:19:52
and you have high risk genetics
1:19:54
I would definitely encourage you to talk to your
1:19:56
ocular oncologist or medical oncologist about it
1:19:58
because certainly it's you know
1:20:00
a good thing to do
1:20:01
both potentially to help yourself and to help science
1:20:04
yeah and just because they haven't worked in the past
1:20:06
doesn't mean that the next one will not work
1:20:09
even if a trial doesn't show that it's effective
1:20:11
for the entire population of patients
1:20:13
that doesn't mean it might not have helped one or two
1:20:15
or three or five patients in the trial
1:20:17
I have several patients who were in adjuvant trials
1:20:20
5to 10 years ago
1:20:21
that have subsequently closed and were negative
1:20:23
but those patients are alive and well
1:20:25
and they are convinced that for themselves
1:20:27
that those approaches did work
1:20:29
and that very well may be true
1:20:30
and so there's lots of great reasons
1:20:32
to try to explore clinical trials
1:20:34
if you're eligible if anybody has old tissue
1:20:36
or is wondering if they have tissue
1:20:38
what's the best way for a patient who is looking for a
1:20:41
an old report maybe
1:20:43
maybe they never got their full report
1:20:45
or they wanna know if there is a sequencing report
1:20:47
they just wanna know what their
1:20:49
I don't know I
1:20:49
I avoided my castle report for a little while
1:20:52
I heard about it and then I put my head in the sand
1:20:54
and I ignored it for like
1:20:55
a year so then I forgot
1:20:56
what did it actually say
1:20:58
so for patients who just wanna see it again
1:21:00
or who wanna know if they could have tissue tested
1:21:01
what's the best way for them to contact Castle
1:21:04
and get that information
1:21:05
you can request a copy of your report
1:21:07
by emailing our clinical services team
1:21:09
and you just need to provide your name
1:21:11
date of birth and the reports that you're looking for
1:21:13
so whether it was the GEP report
1:21:15
Prame Report Sequencing report
1:21:17
or all all of the above
1:21:19
and you can also ask them to check if
1:21:22
if we have residual tissue saved
1:21:24
okay
1:21:24
and then a follow up question to the adjuvant trials
1:21:27
are those trials usually recommended to be um
1:21:31
started or enrolled in
1:21:32
within a specific time frame after diagnosis
1:21:34
Doctor Williams do you know maybe
1:21:36
like
1:21:36
who would be the best person to ask that question to
1:21:38
especially in the case of the quisinostat
1:21:40
is that how you say it our medical oncologists are um
1:21:43
the best ones to talk to about that
1:21:45
so some of it is gonna be dependent upon
1:21:47
when disease started how extensive disease
1:21:50
um sorry
1:21:51
your your genetic uh
1:21:53
profile when you were diagnosed
1:21:54
how far away that was
1:21:56
whether or not you've been enrolled in any other um
1:21:58
clinical trials
1:21:59
but I can put their information in the chat
1:22:03
if that's helpful um
1:22:04
but it is based on a clinical
1:22:06
trial by clinical trial basis
1:22:08
I will say broadly
1:22:08
for adjuvant trials specifically
1:22:10
the majority of them historically
1:22:11
have required the patients enter
1:22:13
within six months
1:22:13
of the time of treatment of the primary tumor
1:22:15
and as Doctor Williams said
1:22:17
there are almost always requirements
1:22:19
for the genetics of the tumor
1:22:20
but in terms of the time frame
1:22:21
it tends to be six months
1:22:23
not always but there is usually a time frame and
1:22:25
and with the idea being
1:22:27
that you wanna get a person enrolled earlier
1:22:30
for the adjuvant therapy to be beneficial
1:22:32
I feel like we have covered so much today
1:22:34
you guys so I really wanna encourage you
1:22:36
if you've been listening to this live
1:22:38
and you wanna come back
1:22:38
and revisit any portion of this recording
1:22:40
please stay tuned
1:22:41
make sure to subscribe on the YouTube channel
1:22:43
because we will have this up later
1:22:45
after it's been edited but
1:22:46
I just want to give a huge shout out to everybody
1:22:48
who's participated with the Q&A
1:22:49
to our doctors who have come on and presented
1:22:52
and also answered all of these questions
1:22:53
throughout the last hour and a half or so
1:22:56
we could not do this without our doctors
1:22:58
who are willing to step up to bat
1:23:00
both for their patients in the research center
1:23:01
like in the COOG studies
1:23:03
I think Doctor Schefler
1:23:04
you shared a picture where it showed like
1:23:05
a lot of the doctors
1:23:06
who are involved in the COOG study
1:23:08
in the Collaborative Ocular Oncology Group
1:23:09
and there are so many physicians out there
1:23:11
who are just so intent
1:23:13
between medical oncologist and ocular oncologist
1:23:15
who are just trying really hard to work together
1:23:18
to bring together the information
1:23:19
and I just
1:23:20
I just wanna give you guys a huge thanks from us
1:23:23
as a community
1:23:24
for collaborating and for working together
1:23:25
to just try and find answers and move us forward on um
1:23:29
on the research pendulum I suppose
1:23:31
what's next what should we be on the lookout for
1:23:34
what are you guys most excited for for COOG
1:23:35
um maybe just give us one little
1:23:37
hopeful teaser that we could look forward to
1:23:39
I think you know
1:23:40
science is slow
1:23:41
it can often be really frustrating for patients to um
1:23:45
waited out for us to you know
1:23:47
get
1:23:47
answers to a lot of these really important questions
1:23:50
I guess I would say you know
1:23:51
as you were saying Danet
1:23:52
everyone should
1:23:53
kind of rest assured that there's a small
1:23:55
but strong community of us who are
1:23:56
you know completely dedicated to this disease
1:23:58
and spend all day long
1:24:00
trying to improve the diagnostics
1:24:03
and prognostics and treatment for this
1:24:04
the COOG2 is really like
1:24:06
the richest data set
1:24:07
that we've ever had in this disease
1:24:08
and it's it's so big and so um
1:24:11
detailed and has so many patients
1:24:12
that it's actually gonna take us
1:24:13
probably a decade to kind of
1:24:15
extract every useful piece of information out of it
1:24:17
so a lot of discoveries are gonna come out of that
1:24:20
over the next 10 years um
1:24:22
and as we continue to follow the patients
1:24:24
who were in the study
1:24:25
and learn more about what happens to them
1:24:27
and the more we understand the genetics of the disease
1:24:29
the more poised we'll be to come up with effective
1:24:32
targeted treatments so
1:24:33
you know I would say the best thing as a patient
1:24:35
is to ask the ocular oncologist
1:24:38
and melanoma oncologist who take care of you
1:24:41
you know kind of
1:24:41
what's the latest coming out of COOG2
1:24:43
if that clinician you know
1:24:46
isn't already sharing that with you spontaneously
1:24:49
and you know
1:24:49
most busy ocular oncologists will know the answer to that
1:24:52
um and kind of also
1:24:53
keeping up to date on the newest
1:24:55
adjuvant and metastatic disease trials
1:24:57
that are coming out that changes
1:24:59
you know almost every quarter
1:25:01
and that's a way to kind of stay on top of things
1:25:03
and the other resource I always point patients to
1:25:06
is if you go to clinicaltrials.gov
1:25:08
which is a free
1:25:09
open website that the National Institute of health runs
1:25:12
and you put in in the little search bar
1:25:15
uveal melanoma or metastatic uveal melanoma
1:25:17
if you have metastatic disease
1:25:18
that will give you a listing
1:25:19
of all of the kind of legitimate
1:25:22
registered prospective
1:25:24
interventional clinical trials in the United States
1:25:26
that are currently open for this disease
1:25:27
and you can actually read about each one
1:25:29
and typically there'll be a contact
1:25:31
email
1:25:31
or phone number for the coordinator for that study
1:25:34
and that's a good way to educate yourself too
1:25:36
yeah I mean I
1:25:37
I think Doctor Schefler stated it perfectly
1:25:39
I will say that personally
1:25:41
you know considering how large the data set is for COOG2
1:25:44
there are a number of individual uh
1:25:47
studies or smaller groups
1:25:49
that we're all kind of
1:25:50
interested in learning more about um
1:25:52
and to kind of understand specific situations
1:25:55
that might apply to smaller subsets of patients
1:25:58
on a kind of a more specific uh
1:26:00
level and I think that'll be really helpful
1:26:02
really exciting um
1:26:03
to kind of utilize this large data set
1:26:06
as the first two studies that have come out have really
1:26:09
um helped to support and validate GEP
1:26:11
and prame and then looked at next generation sequencing
1:26:13
I think the additional studies um
1:26:15
that come out may not um
1:26:17
have as such broad implications
1:26:19
but they will be extremely helpful and very
1:26:21
very interesting to smaller subsets of patients
1:26:23
and smaller types of groups
1:26:24
and there's a number of them that uh
1:26:26
that I'm very interested in looking at as well
1:26:28
so I think tell us
1:26:29
tell us about a couple of those groups
1:26:30
Doctor Williams cause it's actually really fascinating
1:26:33
yeah so I think uh
1:26:34
one for me is
1:26:35
looking at patients
1:26:36
who have ocular dermal melanocytosis
1:26:38
and so um
1:26:39
this is where you have increased pigmentation
1:26:42
in the white part of the eye
1:26:44
and the sclera and the Iris
1:26:45
and in the back part of the eye too
1:26:47
and that predisposes uh
1:26:48
patients to uh
1:26:49
uveal melanoma and so
1:26:51
kind of understanding
1:26:52
what are the molecular characteristics
1:26:54
of people with this condition
1:26:56
and what does that mean I think that's something
1:26:58
that is really really interesting and
1:27:00
and will be helpful for us
1:27:01
to understand that a little bit more
1:27:03
another one uh
1:27:04
that has been discussed is Iris tumors
1:27:06
you know when we talk about uveal melanoma
1:27:08
we are often talking about ciliary
1:27:10
body and choroidal lesions because um
1:27:12
those tend to be the more aggressive ones
1:27:14
and we know that Iris tumors
1:27:16
tend not to be as aggressive
1:27:17
but we don't really have a great understanding
1:27:19
of the molecular profile of those tumors
1:27:21
and I think that's gonna be uh
1:27:23
really helpful and interesting to
1:27:24
to understand that a bit better
1:27:26
excellent you guys
1:27:28
I can't thank you enough for participating
1:27:29
all of you guys in our online audience
1:27:31
as well as our physicians
1:27:32
we're so glad that we can have each of you guys here
1:27:34
today on a Saturday morning
1:27:35
in the middle of the holiday season
1:27:37
so thank you for taking the time out of your day
1:27:39
to just make this possible
1:27:41
and bring us this information
1:27:42
I think there was a patient um
1:27:43
who he mentioned he's 12 or 13 years in the diagnosis
1:27:47
but he's tries to stay up to date
1:27:49
to the new information about uveal melanoma
1:27:52
and I think that's a really uh
1:27:53
just a really strong self advocate of a patient
1:27:57
to be able to do that and to stay in the know and
1:27:59
and to want to stay in the know
1:28:00
so kudos to all of you guys who are here live
1:28:03
share this with a friend or two
1:28:04
once it goes off to the YouTube channel
1:28:07
thanks so much thanks so much for having us
1:28:10
um and just again
1:28:11
huge thank you to Kat
1:28:12
Kat Castle Bio Sciences
1:28:13
Dr. Kat Alsina
1:28:15
did a fantastic job
1:28:16
in compiling all of this information
1:28:17
and just making sure that our presentation
1:28:19
went as seamlessly as possible
1:28:20
so thank you huge thank you to Kat for all of your work
1:28:23
and to everybody who showed up and made this possible
1:28:27
and we will see you guys next time
1:28:29
just as a fun reminder
1:28:31
we do have our sponsors to make this webinar
1:28:34
and our webinar series possible
1:28:35
stay tuned for next year
1:28:36
because we do have some fantastic topics coming to you
1:28:39
in the beginning of 2026
1:28:41
so if you're not already subscribe to the newsletter
1:28:44
the easiest way that you can do that
1:28:45
is to go to our website www.ACureInSight.org
1:28:50
and you're going to hit the top button
1:28:52
there's a little blue button that says
1:28:53
join the newsletter and
1:28:55
this is gonna be a super easy way for you to
1:28:56
stay in the know get all of the um
1:28:59
most up to date registration for upcoming webinars
1:29:02
our upcoming Eye on Mental Health seminar
1:29:04
that's gonna take place at the end of January
1:29:06
as well as our in person patient meeting which
1:29:08
heads up it's happening in Dallas
1:29:10
Texas coming in October of next year
1:29:13
we are so glad
1:29:14
that we have so much participation online
1:29:16
but we just would encourage you guys
1:29:17
consider coming out to the impatient meeting in Dallas
1:29:20
next year make your plans ahead of time
1:29:21
and we would love to see you there
1:29:23
check out the YouTube channel
1:29:24
stay in the know and we will just continue
1:29:27
continue bringing you guys as much content as we can
1:29:30
um with that
1:29:30
I'm gonna go ahead and say goodbye
1:29:34
you guys have been a fantastic audience
1:29:36
and we look forward to seeing you guys next time