WEBVTT

NOTE duration: "01:28:50.773"


NOTE Confidence: 0.9944308

00:00:00.080 --> 00:00:01.599
Program tonight brought to you

NOTE Confidence: 0.9944308

00:00:01.599 --> 00:00:02.420
by a multidisciplinary

NOTE Confidence: 0.91684854

00:00:03.120 --> 00:00:04.080
group to hear from the

NOTE Confidence: 0.91684854

00:00:04.080 --> 00:00:06.740
Smilow Cancer Center encompassing expertise

NOTE Confidence: 0.8906599

00:00:07.040 --> 00:00:08.740
in all of cutaneous

NOTE Confidence: 0.9996069

00:00:09.039 --> 00:00:09.539
oncology.

NOTE Confidence: 0.96585226

00:00:11.200 --> 00:00:12.480
We're gonna start off the

NOTE Confidence: 0.96585226

00:00:12.480 --> 00:00:13.620
session, which really

NOTE Confidence: 0.99885607

00:00:14.025 --> 00:00:14.525
focuses

NOTE Confidence: 0.9527156

00:00:14.825 --> 00:00:16.925
on gene expression and cutaneous

NOTE Confidence: 0.9445303

00:00:17.704 --> 00:00:19.545
malignancies as we've noticed a

NOTE Confidence: 0.9445303

00:00:19.545 --> 00:00:20.985
real uptake in the use

NOTE Confidence: 0.9445303

00:00:20.985 --> 00:00:22.425
of this. And there's been

NOTE Confidence: 0.9445303

00:00:22.425 --> 00:00:24.505
some really great recent data,

NOTE Confidence: 0.9445303

00:00:24.505 --> 00:00:25.544
a flood of it actually

NOTE Confidence: 0.9445303

00:00:25.544 --> 00:00:27.724
recently from randomized controlled trials,

NOTE Confidence: 0.96921134

00:00:28.039 --> 00:00:29.160
as well as some opening

NOTE Confidence: 0.96921134

00:00:29.160 --> 00:00:30.679
of some clinical trials around

NOTE Confidence: 0.96921134

00:00:30.679 --> 00:00:31.339
the country.

NOTE Confidence: 0.9715029

00:00:31.800 --> 00:00:32.680
So we're going to begin

NOTE Confidence: 0.9715029

00:00:32.680 --> 00:00:34.059
our discussion today,

NOTE Confidence: 0.7393066

00:00:34.920 --> 00:00:36.219
with doctor Swoozie.

NOTE Confidence: 0.9936173

00:00:36.680 --> 00:00:37.399
If you'd like to get

NOTE Confidence: 0.9936173

00:00:37.399 --> 00:00:38.540
us started, please.

NOTE Confidence: 0.9732878

00:00:41.175 --> 00:00:41.675
Sure.

NOTE Confidence: 0.9966758

00:00:42.375 --> 00:00:43.995
Just give me one sec.

NOTE Confidence: 0.99394125

00:00:45.734 --> 00:00:46.954
So hi, everyone.

NOTE Confidence: 0.9961433

00:00:48.055 --> 00:00:49.894
Oh, did it stop? Hold

NOTE Confidence: 0.9961433

00:00:49.894 --> 00:00:51.995
on. My screen share stopped.

NOTE Confidence: 0.9961433

00:00:52.055 --> 00:00:53.754
Let me try again here.

NOTE Confidence: 0.99961823

00:00:58.490 --> 00:00:59.390
Here we go.

NOTE Confidence: 0.9575806

00:01:00.010 --> 00:01:01.530
Hi. I'm Katie Swozzi. I'm

NOTE Confidence: 0.9575806

00:01:01.530 --> 00:01:03.390
a Mohsurgent here at Yale,

NOTE Confidence: 0.9575806

00:01:03.610 --> 00:01:04.730
and I'm gonna be starting

NOTE Confidence: 0.9575806

00:01:04.730 --> 00:01:06.250
us off tonight by discussing

NOTE Confidence: 0.9575806

00:01:06.250 --> 00:01:08.090
the role of nomograms and

NOTE Confidence: 0.9575806

00:01:08.090 --> 00:01:08.590
introducing,

NOTE Confidence: 0.9942758

00:01:09.845 --> 00:01:11.284
the idea about gene expression

NOTE Confidence: 0.9942758

00:01:11.284 --> 00:01:13.045
profiling in cutaneous squamous cell

NOTE Confidence: 0.9942758

00:01:13.045 --> 00:01:13.545
carcinoma

NOTE Confidence: 0.9882242

00:01:14.165 --> 00:01:15.604
with a focus on how

NOTE Confidence: 0.9882242

00:01:15.604 --> 00:01:17.444
these tools can help refine

NOTE Confidence: 0.9882242

00:01:17.444 --> 00:01:19.284
risk assessment and clinical decision

NOTE Confidence: 0.9882242

00:01:19.284 --> 00:01:19.784
making.

NOTE Confidence: 0.98806936

00:01:20.405 --> 00:01:22.665
I'll review briefly traditional staging,

NOTE Confidence: 0.98009276

00:01:23.045 --> 00:01:25.340
introduce nomogram based prediction,

NOTE Confidence: 0.9875415

00:01:25.799 --> 00:01:28.040
particularly the risk calculator, and

NOTE Confidence: 0.9875415

00:01:28.040 --> 00:01:29.479
discuss how molecular tools like

NOTE Confidence: 0.9875415

00:01:29.479 --> 00:01:31.580
GEP may further refine risk.

NOTE Confidence: 0.934552

00:01:32.119 --> 00:01:33.959
So although most cutaneous squamous

NOTE Confidence: 0.934552

00:01:33.959 --> 00:01:35.819
cell carcinoma have excellent prognosis,

NOTE Confidence: 0.934552

00:01:36.119 --> 00:01:38.040
a subset behaves aggressively and

NOTE Confidence: 0.934552

00:01:38.040 --> 00:01:39.560
the consequences of missing high

NOTE Confidence: 0.934552

00:01:39.560 --> 00:01:40.575
risk disease are significant.

NOTE Confidence: 0.9327811

00:01:41.615 --> 00:01:43.295
Rates of unfavorable outcomes are

NOTE Confidence: 0.9327811

00:01:43.295 --> 00:01:44.414
about three to five percent

NOTE Confidence: 0.9327811

00:01:44.414 --> 00:01:46.174
for local recurrence, two to

NOTE Confidence: 0.9327811

00:01:46.174 --> 00:01:47.534
five percent for nodal mets,

NOTE Confidence: 0.9327811

00:01:47.534 --> 00:01:48.655
and one point five to

NOTE Confidence: 0.9327811

00:01:48.655 --> 00:01:49.854
three point five percent for

NOTE Confidence: 0.9327811

00:01:49.854 --> 00:01:52.094
disease specific death. And despite

NOTE Confidence: 0.9327811

00:01:52.094 --> 00:01:53.935
these relatively small percentages, the

NOTE Confidence: 0.9327811

00:01:53.935 --> 00:01:54.435
absolute

NOTE Confidence: 0.9697068

00:01:54.850 --> 00:01:56.370
mortality from cutaneous squamous cell

NOTE Confidence: 0.9697068

00:01:56.370 --> 00:01:57.510
carcinoma is substantial,

NOTE Confidence: 0.9785247

00:01:58.610 --> 00:02:00.070
meeting at least meeting,

NOTE Confidence: 0.9525283

00:02:00.450 --> 00:02:01.970
but, and by most models

NOTE Confidence: 0.9525283

00:02:01.970 --> 00:02:03.510
exceeding that of melanoma.

NOTE Confidence: 0.9574942

00:02:04.370 --> 00:02:05.570
So I did talk about

NOTE Confidence: 0.9574942

00:02:05.570 --> 00:02:06.770
staging in the last one

NOTE Confidence: 0.9574942

00:02:06.770 --> 00:02:07.570
of these sessions, but I

NOTE Confidence: 0.9574942

00:02:07.570 --> 00:02:09.090
did wanna briefly bring it

NOTE Confidence: 0.9574942

00:02:09.090 --> 00:02:10.305
up here. So first here,

NOTE Confidence: 0.9574942

00:02:10.305 --> 00:02:12.185
I'm showing AJCC eight.

NOTE Confidence: 0.9858774

00:02:13.044 --> 00:02:15.465
Staging and, the eighth edition

NOTE Confidence: 0.9858774

00:02:15.685 --> 00:02:17.525
for head and neck cutaneous

NOTE Confidence: 0.9858774

00:02:17.525 --> 00:02:18.505
squamous cell carcinoma

NOTE Confidence: 0.992482

00:02:19.044 --> 00:02:20.985
attempted to improve risk stratification

NOTE Confidence: 0.997005

00:02:21.285 --> 00:02:23.385
by expanding the t three

NOTE Confidence: 0.997005

00:02:23.445 --> 00:02:25.860
group to include deep invasion,

NOTE Confidence: 0.97777414

00:02:26.560 --> 00:02:28.880
perineural invasion, and minor bone

NOTE Confidence: 0.97777414

00:02:28.880 --> 00:02:29.380
erosion.

NOTE Confidence: 0.9804423

00:02:30.240 --> 00:02:31.200
And one of the major

NOTE Confidence: 0.9804423

00:02:31.200 --> 00:02:33.460
improvements compared with AJCC seven

NOTE Confidence: 0.9804423

00:02:33.520 --> 00:02:34.800
was that core outcomes are

NOTE Confidence: 0.9804423

00:02:34.800 --> 00:02:36.480
now concentrated in t three

NOTE Confidence: 0.9804423

00:02:36.480 --> 00:02:37.700
and t four tumors

NOTE Confidence: 0.96357363

00:02:38.025 --> 00:02:39.565
rather than across a heterogeneic,

NOTE Confidence: 0.99786055

00:02:40.345 --> 00:02:41.245
T2 group.

NOTE Confidence: 0.9520416

00:02:41.625 --> 00:02:43.325
However, even with AJCC8,

NOTE Confidence: 0.86387366

00:02:43.705 --> 00:02:44.764
there remains substantial

NOTE Confidence: 0.8772955

00:02:45.065 --> 00:02:46.365
variability in outcomes.

NOTE Confidence: 0.93757427

00:02:46.985 --> 00:02:48.185
So the Brigham and Women's

NOTE Confidence: 0.93757427

00:02:48.185 --> 00:02:50.105
Staging System was developed to

NOTE Confidence: 0.93757427

00:02:50.105 --> 00:02:51.325
address this heterogeneity.

NOTE Confidence: 0.9947221

00:02:52.330 --> 00:02:53.069
This model,

NOTE Confidence: 0.9749539

00:02:53.690 --> 00:02:55.470
identifies four major risk factors,

NOTE Confidence: 0.9749539

00:02:55.530 --> 00:02:56.030
diameter,

NOTE Confidence: 0.98207414

00:02:56.489 --> 00:02:58.889
depth, beyond fat, perineural invasion

NOTE Confidence: 0.98207414

00:02:58.889 --> 00:02:59.690
of greater than point one

NOTE Confidence: 0.98207414

00:02:59.690 --> 00:03:01.870
millimeters, and poorly differentiated histology.

NOTE Confidence: 0.9741505

00:03:03.290 --> 00:03:04.669
And tumors are then classified

NOTE Confidence: 0.9741505

00:03:04.730 --> 00:03:05.690
by their number of risk

NOTE Confidence: 0.9741505

00:03:05.690 --> 00:03:07.544
factors into t one, t

NOTE Confidence: 0.9741505

00:03:07.544 --> 00:03:08.584
two a, t two b,

NOTE Confidence: 0.9741505

00:03:08.584 --> 00:03:09.484
and t three.

NOTE Confidence: 0.9471105

00:03:09.944 --> 00:03:11.385
And Brigham and Women's Staging

NOTE Confidence: 0.9471105

00:03:11.385 --> 00:03:13.165
shows better risk stratification

NOTE Confidence: 0.964483

00:03:13.784 --> 00:03:15.305
at, t two, t three,

NOTE Confidence: 0.964483

00:03:15.305 --> 00:03:16.344
and here you can see

NOTE Confidence: 0.964483

00:03:16.344 --> 00:03:18.105
that t two b tumors

NOTE Confidence: 0.964483

00:03:18.105 --> 00:03:19.305
have about a twenty percent

NOTE Confidence: 0.964483

00:03:19.305 --> 00:03:20.584
risk of local recurrence and

NOTE Confidence: 0.964483

00:03:20.584 --> 00:03:21.325
nodal metastasis

NOTE Confidence: 0.9273379

00:03:21.625 --> 00:03:22.844
with t two a,

NOTE Confidence: 0.94820297

00:03:23.430 --> 00:03:24.650
ten percent or below.

NOTE Confidence: 0.9641098

00:03:25.270 --> 00:03:26.150
And you can see there's,

NOTE Confidence: 0.9641098

00:03:26.550 --> 00:03:27.450
less stratification,

NOTE Confidence: 0.87085444

00:03:28.069 --> 00:03:28.810
in AGCC

NOTE Confidence: 0.94474065

00:03:29.110 --> 00:03:31.050
eight, between t three,

NOTE Confidence: 0.99444586

00:03:32.230 --> 00:03:33.129
and t two.

NOTE Confidence: 0.9879744

00:03:33.430 --> 00:03:35.110
And so this improved risk

NOTE Confidence: 0.9879744

00:03:35.110 --> 00:03:37.530
stratification, but staging remains categorical

NOTE Confidence: 0.9879744

00:03:37.750 --> 00:03:38.890
rather than individualized.

NOTE Confidence: 0.9917042

00:03:39.725 --> 00:03:40.465
So NCCN

NOTE Confidence: 0.9807783

00:03:40.765 --> 00:03:42.845
guidelines build further on staging

NOTE Confidence: 0.9807783

00:03:42.845 --> 00:03:43.985
incorporating additional

NOTE Confidence: 0.97177076

00:03:44.365 --> 00:03:45.965
high risk features and patient

NOTE Confidence: 0.97177076

00:03:45.965 --> 00:03:47.805
specific features such as, you

NOTE Confidence: 0.97177076

00:03:47.805 --> 00:03:49.165
know, is the tumor primary

NOTE Confidence: 0.97177076

00:03:49.165 --> 00:03:50.865
recurrent? Is the patient immunosuppressed?

NOTE Confidence: 0.99525183

00:03:51.530 --> 00:03:53.230
Is the location on previously

NOTE Confidence: 0.9793744

00:03:53.770 --> 00:03:55.849
irradiated skin? What is the

NOTE Confidence: 0.9793744

00:03:55.849 --> 00:03:57.310
growth rate of the tumor?

NOTE Confidence: 0.97329545

00:03:58.010 --> 00:03:59.790
And also incorporates different,

NOTE Confidence: 0.9113143

00:04:00.330 --> 00:04:01.550
histologic subtypes.

NOTE Confidence: 0.9912645

00:04:02.810 --> 00:04:05.050
And NCCN classification is useful,

NOTE Confidence: 0.9912645

00:04:05.050 --> 00:04:06.435
but it still groups patients

NOTE Confidence: 0.9912645

00:04:06.435 --> 00:04:07.795
into low, high risk, and

NOTE Confidence: 0.9912645

00:04:07.795 --> 00:04:09.395
very high risk rather than

NOTE Confidence: 0.9912645

00:04:09.395 --> 00:04:11.175
generating individual probabilities.

NOTE Confidence: 0.97806466

00:04:13.075 --> 00:04:13.895
So nomograms,

NOTE Confidence: 0.99841464

00:04:14.915 --> 00:04:16.115
this is where nomograms are

NOTE Confidence: 0.99841464

00:04:16.115 --> 00:04:17.895
particularly helpful. So a nomogram

NOTE Confidence: 0.99841464

00:04:17.955 --> 00:04:19.875
is a statistical model that

NOTE Confidence: 0.99841464

00:04:19.875 --> 00:04:22.270
integrates multiple variables to generate

NOTE Confidence: 0.99841464

00:04:22.270 --> 00:04:23.009
an individualized

NOTE Confidence: 0.84606457

00:04:23.310 --> 00:04:24.690
probability of prosthesis

NOTE Confidence: 0.957441

00:04:25.389 --> 00:04:26.050
or death.

NOTE Confidence: 0.9848068

00:04:26.350 --> 00:04:28.289
And unlike staging systems, nomograms

NOTE Confidence: 0.9848068

00:04:28.350 --> 00:04:30.669
produce continuous risk estimates rather

NOTE Confidence: 0.9848068

00:04:30.669 --> 00:04:31.410
than categories.

NOTE Confidence: 0.9706755

00:04:31.789 --> 00:04:33.150
And this is especially useful

NOTE Confidence: 0.9706755

00:04:33.150 --> 00:04:35.065
in gray zones. For example,

NOTE Confidence: 0.9706755

00:04:35.125 --> 00:04:36.645
tumors that fall between Brigham

NOTE Confidence: 0.9706755

00:04:36.645 --> 00:04:38.005
and Women staging t two

NOTE Confidence: 0.9706755

00:04:38.005 --> 00:04:39.044
a and t two b,

NOTE Confidence: 0.9706755

00:04:39.044 --> 00:04:40.485
which we commonly refer to

NOTE Confidence: 0.9706755

00:04:40.485 --> 00:04:41.945
as t two a plus.

NOTE Confidence: 0.9764063

00:04:43.685 --> 00:04:45.625
Nomograms can also be, presented

NOTE Confidence: 0.9764063

00:04:45.764 --> 00:04:46.264
graphically

NOTE Confidence: 0.9973563

00:04:46.645 --> 00:04:48.104
or embedded in calculators,

NOTE Confidence: 0.9993594

00:04:48.645 --> 00:04:49.945
making them very clinically

NOTE Confidence: 0.98543584

00:04:50.970 --> 00:04:51.790
practical. So,

NOTE Confidence: 0.8885025

00:04:52.410 --> 00:04:53.950
I briefly mentioned this nomogram,

NOTE Confidence: 0.9645405

00:04:54.810 --> 00:04:56.890
for cutaneous SCC that predicts

NOTE Confidence: 0.9645405

00:04:56.890 --> 00:04:58.490
the risk of recurrence after

NOTE Confidence: 0.9645405

00:04:58.490 --> 00:05:00.330
MOSE, which was published in

NOTE Confidence: 0.9645405

00:05:00.330 --> 00:05:02.010
twenty twenty two, combining clinical

NOTE Confidence: 0.9645405

00:05:02.010 --> 00:05:03.390
factors with two biomarkers,

NOTE Confidence: 0.9804055

00:05:03.964 --> 00:05:05.005
and here showing the type

NOTE Confidence: 0.9804055

00:05:05.005 --> 00:05:06.605
of graphical representation of the

NOTE Confidence: 0.9804055

00:05:06.605 --> 00:05:07.805
nomogram. But the one I

NOTE Confidence: 0.9804055

00:05:07.805 --> 00:05:09.005
wanted to focus on is

NOTE Confidence: 0.9804055

00:05:09.005 --> 00:05:11.165
the, risk calculator, which was

NOTE Confidence: 0.9804055

00:05:11.165 --> 00:05:12.145
developed by,

NOTE Confidence: 0.8725278

00:05:12.765 --> 00:05:13.964
number of doctor Krishnan and

NOTE Confidence: 0.8725278

00:05:13.964 --> 00:05:15.325
I's colleagues in the Mose

NOTE Confidence: 0.8725278

00:05:15.325 --> 00:05:16.205
College. And,

NOTE Confidence: 0.9967947

00:05:17.449 --> 00:05:19.790
it's a clinically practical nomogram

NOTE Confidence: 0.9581234

00:05:20.410 --> 00:05:22.270
used to predict metastatic risk,

NOTE Confidence: 0.9581234

00:05:22.330 --> 00:05:23.770
and it's also available in

NOTE Confidence: 0.9581234

00:05:23.770 --> 00:05:25.210
an app form that's very,

NOTE Confidence: 0.9581234

00:05:25.610 --> 00:05:26.430
user friendly.

NOTE Confidence: 0.9825738

00:05:26.810 --> 00:05:27.930
So I wanted to show

NOTE Confidence: 0.9825738

00:05:27.930 --> 00:05:29.529
you the risk calculator using

NOTE Confidence: 0.9825738

00:05:29.529 --> 00:05:30.810
a case I recently saw

NOTE Confidence: 0.9825738

00:05:30.810 --> 00:05:31.955
in clinic. So here's a

NOTE Confidence: 0.9825738

00:05:31.955 --> 00:05:33.154
patient who presented for a

NOTE Confidence: 0.9825738

00:05:33.154 --> 00:05:34.595
treatment of a cutaneous squamous

NOTE Confidence: 0.9825738

00:05:34.595 --> 00:05:35.254
cell carcinoma,

NOTE Confidence: 0.9729235

00:05:35.555 --> 00:05:37.095
the right preauricular region.

NOTE Confidence: 0.9391347

00:05:37.955 --> 00:05:39.574
And here was her PRIMOs,

NOTE Confidence: 0.96749276

00:05:40.675 --> 00:05:42.435
lesion and here's her post

NOTE Confidence: 0.96749276

00:05:42.435 --> 00:05:44.194
MOS defect. And so when

NOTE Confidence: 0.96749276

00:05:44.194 --> 00:05:45.395
you look at staging for

NOTE Confidence: 0.96749276

00:05:45.395 --> 00:05:46.835
her, her PRIMO size was

NOTE Confidence: 0.96749276

00:05:46.835 --> 00:05:48.650
one point five centimeters. She

NOTE Confidence: 0.96749276

00:05:48.650 --> 00:05:50.650
had very widespread perineural invasion,

NOTE Confidence: 0.96749276

00:05:50.650 --> 00:05:51.610
but it was all small

NOTE Confidence: 0.96749276

00:05:51.610 --> 00:05:52.110
caliber,

NOTE Confidence: 0.9573444

00:05:52.410 --> 00:05:53.449
and she did have poorly

NOTE Confidence: 0.9573444

00:05:53.449 --> 00:05:55.790
differentiated histology. So, by staging,

NOTE Confidence: 0.9573444

00:05:55.850 --> 00:05:57.150
she's either AJCCA

NOTE Confidence: 0.96517915

00:05:57.529 --> 00:05:58.830
T1 or T2A,

NOTE Confidence: 0.9618012

00:05:59.290 --> 00:06:00.250
but you just know this

NOTE Confidence: 0.9618012

00:06:00.250 --> 00:06:01.529
patient is not going to

NOTE Confidence: 0.9618012

00:06:01.529 --> 00:06:02.510
do well. And,

NOTE Confidence: 0.99360335

00:06:02.835 --> 00:06:04.375
that that staging is underrepresenting

NOTE Confidence: 0.99360335

00:06:04.675 --> 00:06:06.055
the biology of her disease.

NOTE Confidence: 0.9795102

00:06:06.435 --> 00:06:07.555
So let's put her in

NOTE Confidence: 0.9795102

00:06:07.555 --> 00:06:09.154
the risk calculator. So here,

NOTE Confidence: 0.9795102

00:06:09.154 --> 00:06:10.115
if we add,

NOTE Confidence: 0.9775658

00:06:10.755 --> 00:06:11.575
her criteria,

NOTE Confidence: 0.9092451

00:06:12.835 --> 00:06:13.955
here, you see she's gonna

NOTE Confidence: 0.9092451

00:06:13.955 --> 00:06:15.095
get credit for a perineural

NOTE Confidence: 0.9092451

00:06:15.154 --> 00:06:16.980
invasion for the depth of

NOTE Confidence: 0.9092451

00:06:16.980 --> 00:06:17.480
invasion.

NOTE Confidence: 0.8841126

00:06:18.180 --> 00:06:18.500
And,

NOTE Confidence: 0.9503506

00:06:19.060 --> 00:06:20.420
we look at her risk

NOTE Confidence: 0.9503506

00:06:20.420 --> 00:06:22.339
calculator, it's gonna reflect a

NOTE Confidence: 0.9503506

00:06:22.339 --> 00:06:23.960
lot higher than her staging,

NOTE Confidence: 0.8322955

00:06:25.460 --> 00:06:26.520
her risk of neurotoxicity

NOTE Confidence: 0.9473152

00:06:27.140 --> 00:06:29.675
being, over thirteen percent and,

NOTE Confidence: 0.9260937

00:06:30.375 --> 00:06:31.735
recurrence after mood was about

NOTE Confidence: 0.9260937

00:06:31.735 --> 00:06:33.014
twenty percent. So this patient

NOTE Confidence: 0.9260937

00:06:33.014 --> 00:06:34.235
will go to our multidisciplinary

NOTE Confidence: 0.98661906

00:06:34.694 --> 00:06:36.694
tumor board for consideration of

NOTE Confidence: 0.98661906

00:06:36.694 --> 00:06:37.194
adjuvant,

NOTE Confidence: 0.9789959

00:06:37.815 --> 00:06:39.335
therapy where her staging may

NOTE Confidence: 0.9789959

00:06:39.335 --> 00:06:41.034
not have triggered that alone.

NOTE Confidence: 0.9981924

00:06:42.060 --> 00:06:43.500
So I'm briefly just gonna

NOTE Confidence: 0.9981924

00:06:43.500 --> 00:06:44.060
talk about,

NOTE Confidence: 0.95426625

00:06:44.460 --> 00:06:45.740
GP because doctor Roach is

NOTE Confidence: 0.95426625

00:06:45.740 --> 00:06:47.279
gonna build on this. But,

NOTE Confidence: 0.97401714

00:06:47.659 --> 00:06:49.180
for cutaneous SCC, we have

NOTE Confidence: 0.97401714

00:06:49.180 --> 00:06:50.479
a forty gene expression,

NOTE Confidence: 0.99826115

00:06:50.860 --> 00:06:52.879
profile test that's clinically available.

NOTE Confidence: 0.9236546

00:06:54.060 --> 00:06:55.900
This was generated from primary

NOTE Confidence: 0.9236546

00:06:55.900 --> 00:06:58.215
cutaneous bimicile carcinomas with known

NOTE Confidence: 0.9236546

00:06:58.215 --> 00:06:59.915
outcomes, so retrospectives,

NOTE Confidence: 0.9798005

00:07:00.935 --> 00:07:01.675
we developed,

NOTE Confidence: 0.99051964

00:07:02.855 --> 00:07:04.475
and has not been prospectively,

NOTE Confidence: 0.908134

00:07:06.055 --> 00:07:08.055
validated yet, but identifies three

NOTE Confidence: 0.908134

00:07:08.055 --> 00:07:10.295
classes, class one, two a,

NOTE Confidence: 0.908134

00:07:10.295 --> 00:07:11.530
and two b, the different

NOTE Confidence: 0.908134

00:07:11.530 --> 00:07:13.150
likelihoods of developing metastasis,

NOTE Confidence: 0.9958903

00:07:14.010 --> 00:07:14.990
at three years.

NOTE Confidence: 0.9461675

00:07:15.450 --> 00:07:16.490
Oh, sorry, this slide looks

NOTE Confidence: 0.9461675

00:07:16.490 --> 00:07:16.990
weird.

NOTE Confidence: 0.9555574

00:07:17.610 --> 00:07:19.290
So, the three classes, Class

NOTE Confidence: 0.9555574

00:07:19.290 --> 00:07:20.590
I is the low biological

NOTE Confidence: 0.9555574

00:07:20.730 --> 00:07:21.770
risk and is about half

NOTE Confidence: 0.9555574

00:07:21.770 --> 00:07:22.750
the study population,

NOTE Confidence: 0.94150627

00:07:23.395 --> 00:07:24.835
Class two a is moderate

NOTE Confidence: 0.94150627

00:07:24.835 --> 00:07:26.435
biologic risk, and, when you

NOTE Confidence: 0.94150627

00:07:26.435 --> 00:07:27.735
look at the hazard ratio

NOTE Confidence: 0.94150627

00:07:27.955 --> 00:07:29.235
here, it's similar to the

NOTE Confidence: 0.94150627

00:07:29.235 --> 00:07:31.794
strongest traditional clinical pathologic factors

NOTE Confidence: 0.94150627

00:07:31.794 --> 00:07:33.814
like perineural invasion, for example.

NOTE Confidence: 0.97994375

00:07:34.115 --> 00:07:35.155
And class two b is

NOTE Confidence: 0.97994375

00:07:35.155 --> 00:07:36.194
very high risk with a

NOTE Confidence: 0.97994375

00:07:36.194 --> 00:07:37.560
greater than fifty percent risk

NOTE Confidence: 0.97994375

00:07:37.639 --> 00:07:39.080
of metastasis, and you could

NOTE Confidence: 0.97994375

00:07:39.080 --> 00:07:40.060
see that here.

NOTE Confidence: 0.72330844

00:07:41.960 --> 00:07:42.460
So,

NOTE Confidence: 0.9763164

00:07:43.080 --> 00:07:43.960
about a third of the

NOTE Confidence: 0.9763164

00:07:43.960 --> 00:07:45.560
cases will end up, t

NOTE Confidence: 0.9763164

00:07:45.560 --> 00:07:46.620
two a. And so,

NOTE Confidence: 0.9682206

00:07:47.000 --> 00:07:48.200
well, doctor Roche is gonna

NOTE Confidence: 0.9682206

00:07:48.200 --> 00:07:49.400
talk more about what we

NOTE Confidence: 0.9682206

00:07:49.400 --> 00:07:51.240
do, with those tumors, and

NOTE Confidence: 0.9682206

00:07:51.240 --> 00:07:52.620
this is where, you know,

NOTE Confidence: 0.94754255

00:07:53.675 --> 00:07:55.694
correlation with staging is also,

NOTE Confidence: 0.98972434

00:07:56.794 --> 00:07:58.555
important. And so, you know,

NOTE Confidence: 0.98972434

00:07:58.555 --> 00:07:59.914
what are the takeaways here?

NOTE Confidence: 0.98972434

00:08:00.235 --> 00:08:01.675
Cutaneous squamous cell carcinoma is

NOTE Confidence: 0.98972434

00:08:01.675 --> 00:08:02.335
a heterogeneous

NOTE Confidence: 0.8549165

00:08:04.395 --> 00:08:06.095
group, and, accurate

NOTE Confidence: 0.9990314

00:08:06.450 --> 00:08:08.150
risk stratification is critical.

NOTE Confidence: 0.9688016

00:08:08.610 --> 00:08:10.610
Nomograms such as risk provide

NOTE Confidence: 0.9688016

00:08:10.610 --> 00:08:12.710
individual risk prediction and particularly

NOTE Confidence: 0.9688016

00:08:12.770 --> 00:08:13.970
helpful in these gray zone

NOTE Confidence: 0.9688016

00:08:13.970 --> 00:08:16.550
cases, and gene expression profiling

NOTE Confidence: 0.85443926

00:08:17.090 --> 00:08:19.250
adds biologic risk information that

NOTE Confidence: 0.85443926

00:08:19.250 --> 00:08:19.615
may further refine management. And

NOTE Confidence: 0.85443926

00:08:19.615 --> 00:08:19.672
to further speak about that,

NOTE Confidence: 0.85443926

00:08:19.684 --> 00:08:20.230
I'm gonna turn it over

NOTE Confidence: 0.56268066

00:08:20.690 --> 00:08:20.715
to

NOTE Confidence: 0.9825039

00:08:29.275 --> 00:08:30.335
Thank you, Katie.

NOTE Confidence: 0.8931605

00:08:30.635 --> 00:08:32.154
Alright. Let's pull mine out

NOTE Confidence: 0.8931605

00:08:32.154 --> 00:08:32.654
here.

NOTE Confidence: 0.89928687

00:08:34.170 --> 00:08:36.350
Share. Presenter mode. Okay.

NOTE Confidence: 0.9524986

00:08:37.210 --> 00:08:39.290
Alright. So I'm Ansley Roach.

NOTE Confidence: 0.9524986

00:08:39.290 --> 00:08:40.010
I'm a head and neck

NOTE Confidence: 0.9524986

00:08:40.010 --> 00:08:40.910
surgeon here.

NOTE Confidence: 0.99012977

00:08:42.250 --> 00:08:43.710
I'm gonna be just speaking

NOTE Confidence: 0.99012977

00:08:43.770 --> 00:08:44.910
specifically about,

NOTE Confidence: 0.96269315

00:08:45.610 --> 00:08:48.115
this forty GEP panel and,

NOTE Confidence: 0.96269315

00:08:48.514 --> 00:08:49.795
also as it pertains to

NOTE Confidence: 0.96269315

00:08:49.795 --> 00:08:50.694
the head and neck.

NOTE Confidence: 0.97384167

00:08:51.074 --> 00:08:51.954
But talking a little bit

NOTE Confidence: 0.97384167

00:08:51.954 --> 00:08:53.154
about its development, because I

NOTE Confidence: 0.97384167

00:08:53.154 --> 00:08:54.274
think it's important to just

NOTE Confidence: 0.97384167

00:08:54.274 --> 00:08:56.054
get an understanding of what

NOTE Confidence: 0.9188383

00:08:56.595 --> 00:08:57.795
of what this, how this

NOTE Confidence: 0.9188383

00:08:57.795 --> 00:08:59.714
was validated. So just to

NOTE Confidence: 0.9188383

00:08:59.714 --> 00:09:00.834
recap some of the things

NOTE Confidence: 0.9188383

00:09:00.834 --> 00:09:02.214
that Doctor. Swozi mentioned,

NOTE Confidence: 0.96751225

00:09:03.330 --> 00:09:04.929
the high risk features that

NOTE Confidence: 0.96751225

00:09:04.929 --> 00:09:06.309
we see in these patients

NOTE Confidence: 0.96751225

00:09:06.450 --> 00:09:07.970
can vary or can be,

NOTE Confidence: 0.96751225

00:09:08.290 --> 00:09:10.150
attributed to the tumor characteristics

NOTE Confidence: 0.96751225

00:09:10.210 --> 00:09:11.570
themselves. And I've listed them

NOTE Confidence: 0.96751225

00:09:11.570 --> 00:09:13.410
here. Essentially, anything greater than

NOTE Confidence: 0.96751225

00:09:13.410 --> 00:09:15.170
two centimeters depth of invasion

NOTE Confidence: 0.96751225

00:09:15.170 --> 00:09:16.850
beyond the subcutaneous fat or

NOTE Confidence: 0.96751225

00:09:16.850 --> 00:09:17.670
six millimeters.

NOTE Confidence: 0.89027077

00:09:18.084 --> 00:09:19.765
Higher risk areas, so specifically

NOTE Confidence: 0.89027077

00:09:19.765 --> 00:09:21.205
the head and neck, hands,

NOTE Confidence: 0.89027077

00:09:21.205 --> 00:09:22.725
feet, the pre tibial region,

NOTE Confidence: 0.89027077

00:09:22.725 --> 00:09:23.845
and the anal genital re

NOTE Confidence: 0.89027077

00:09:23.925 --> 00:09:25.065
reach, areas,

NOTE Confidence: 0.9565836

00:09:26.005 --> 00:09:27.925
poorly defined borders. Reshare your

NOTE Confidence: 0.9565836

00:09:27.925 --> 00:09:29.205
screen? I think it's not

NOTE Confidence: 0.9565836

00:09:29.205 --> 00:09:30.265
showing up. Sorry.

NOTE Confidence: 0.9995314

00:09:30.644 --> 00:09:32.245
That's okay. Thank you. Sorry.

NOTE Confidence: 0.9995314

00:09:32.245 --> 00:09:33.144
Let's see.

NOTE Confidence: 0.9973364

00:09:34.679 --> 00:09:35.179
Okay.

NOTE Confidence: 0.9975297

00:09:36.600 --> 00:09:38.220
Share. Sorry about that.

NOTE Confidence: 0.97664255

00:09:39.880 --> 00:09:41.240
What about this? Is that

NOTE Confidence: 0.97664255

00:09:41.240 --> 00:09:42.440
good? Okay. Is it in

NOTE Confidence: 0.97664255

00:09:42.440 --> 00:09:43.880
presenter mode? Or No. So

NOTE Confidence: 0.97664255

00:09:43.880 --> 00:09:44.760
if you go up and

NOTE Confidence: 0.97664255

00:09:44.760 --> 00:09:45.640
you could put it in

NOTE Confidence: 0.97664255

00:09:45.640 --> 00:09:46.540
presenter mode.

NOTE Confidence: 0.84116185

00:09:47.634 --> 00:09:48.714
Do I do that through

NOTE Confidence: 0.84116185

00:09:49.074 --> 00:09:49.894
right there.

NOTE Confidence: 0.9411648

00:09:51.714 --> 00:09:52.995
If you hit slideshow and

NOTE Confidence: 0.9411648

00:09:52.995 --> 00:09:53.634
then say,

NOTE Confidence: 0.76799935

00:09:56.514 --> 00:09:56.755
view

NOTE Confidence: 0.81473243

00:09:57.634 --> 00:09:59.654
I'm not saying Exit animation.

NOTE Confidence: 0.99907994

00:10:02.990 --> 00:10:04.050
What about this?

NOTE Confidence: 0.9247667

00:10:04.990 --> 00:10:06.110
No. It just doesn't know.

NOTE Confidence: 0.9247667

00:10:06.270 --> 00:10:07.709
Stopped. Okay. Sorry. So I'm

NOTE Confidence: 0.9247667

00:10:07.709 --> 00:10:08.910
just gonna do it old

NOTE Confidence: 0.9247667

00:10:08.910 --> 00:10:09.410
school.

NOTE Confidence: 0.9044393

00:10:11.390 --> 00:10:12.830
Yes. That? Okay. I'm not

NOTE Confidence: 0.9044393

00:10:13.230 --> 00:10:14.350
okay. Great. Thank you. Sorry

NOTE Confidence: 0.9044393

00:10:14.350 --> 00:10:15.089
about that.

NOTE Confidence: 0.8789857

00:10:16.404 --> 00:10:17.785
And then, also

NOTE Confidence: 0.89384085

00:10:18.324 --> 00:10:19.545
indications of,

NOTE Confidence: 0.8834867

00:10:20.165 --> 00:10:22.485
perineural invasion such as pain

NOTE Confidence: 0.8834867

00:10:22.485 --> 00:10:24.884
or paresthesias or, paresis or

NOTE Confidence: 0.8834867

00:10:24.884 --> 00:10:25.384
paralysis,

NOTE Confidence: 0.97085077

00:10:27.045 --> 00:10:27.545
histopathologic

NOTE Confidence: 0.85007495

00:10:28.084 --> 00:10:29.785
features, so just different histopathologic

NOTE Confidence: 0.9561045

00:10:30.245 --> 00:10:31.939
subtypes of squamous cell carcinoma,

NOTE Confidence: 0.9561045

00:10:32.160 --> 00:10:33.699
certainly the PNI and LVI

NOTE Confidence: 0.9561045

00:10:33.759 --> 00:10:35.360
that Doctor. Swozi mentioned, and

NOTE Confidence: 0.9561045

00:10:35.360 --> 00:10:37.040
then patient factors. These all

NOTE Confidence: 0.9561045

00:10:37.040 --> 00:10:38.660
place patients at high risk,

NOTE Confidence: 0.97252584

00:10:39.360 --> 00:10:41.519
for metastasis, local recurrence of

NOTE Confidence: 0.97252584

00:10:41.519 --> 00:10:42.579
squamous cell carcinoma.

NOTE Confidence: 0.9320314

00:10:44.575 --> 00:10:46.495
As in other disease states

NOTE Confidence: 0.9320314

00:10:46.495 --> 00:10:47.795
such as breast cancer,

NOTE Confidence: 0.9618928

00:10:48.975 --> 00:10:50.035
there have been,

NOTE Confidence: 0.8436408

00:10:50.575 --> 00:10:51.715
a a burgeoning

NOTE Confidence: 0.9750838

00:10:52.095 --> 00:10:54.595
field of gene expression profiling,

NOTE Confidence: 0.95208865

00:10:55.790 --> 00:10:57.389
in which a essentially, a

NOTE Confidence: 0.95208865

00:10:57.389 --> 00:10:59.490
proprietary algorithm is used,

NOTE Confidence: 0.9981895

00:10:59.870 --> 00:11:02.029
to predict metastatic risk or

NOTE Confidence: 0.9981895

00:11:02.029 --> 00:11:02.929
risk of recurrence.

NOTE Confidence: 0.9673218

00:11:03.630 --> 00:11:04.829
In this there's one that's

NOTE Confidence: 0.9673218

00:11:04.829 --> 00:11:06.429
commercially available for squamous cell

NOTE Confidence: 0.9673218

00:11:06.429 --> 00:11:07.949
carcinoma. It's a forty gene

NOTE Confidence: 0.9673218

00:11:07.949 --> 00:11:08.449
panel.

NOTE Confidence: 0.95700395

00:11:09.165 --> 00:11:10.684
They use two gene expression

NOTE Confidence: 0.95700395

00:11:10.684 --> 00:11:12.524
signatures. There are thirty four,

NOTE Confidence: 0.95700395

00:11:12.845 --> 00:11:14.605
discriminant genes. They're all listed

NOTE Confidence: 0.95700395

00:11:14.605 --> 00:11:15.725
here. It's kind of a

NOTE Confidence: 0.95700395

00:11:15.725 --> 00:11:17.245
a variety of different sorts

NOTE Confidence: 0.95700395

00:11:17.245 --> 00:11:18.705
of genes they're looking for,

NOTE Confidence: 0.9484004

00:11:19.165 --> 00:11:19.665
MMPs,

NOTE Confidence: 0.9798319

00:11:20.205 --> 00:11:23.005
metabolic related proteins, transcription factors,

NOTE Confidence: 0.9798319

00:11:23.005 --> 00:11:24.625
and then some control genes.

NOTE Confidence: 0.9798319

00:11:24.900 --> 00:11:26.500
And these this testing can

NOTE Confidence: 0.9798319

00:11:26.500 --> 00:11:28.280
be done on archived FFPE

NOTE Confidence: 0.9798319

00:11:28.420 --> 00:11:29.380
samples, so it does not

NOTE Confidence: 0.9798319

00:11:29.380 --> 00:11:30.580
have to be on fresh

NOTE Confidence: 0.9798319

00:11:30.580 --> 00:11:31.080
tumor.

NOTE Confidence: 0.99084115

00:11:32.740 --> 00:11:34.760
The this test was,

NOTE Confidence: 0.85585946

00:11:35.300 --> 00:11:37.059
developed and as doctor Swozi

NOTE Confidence: 0.85585946

00:11:37.059 --> 00:11:38.840
said, in a retrospective fashion

NOTE Confidence: 0.96431947

00:11:39.345 --> 00:11:39.845
where,

NOTE Confidence: 0.9980084

00:11:41.345 --> 00:11:43.204
long term outcomes were available

NOTE Confidence: 0.9980084

00:11:43.425 --> 00:11:45.024
and evaluated as part of

NOTE Confidence: 0.9980084

00:11:45.024 --> 00:11:46.245
the validation cohort.

NOTE Confidence: 0.9325591

00:11:47.264 --> 00:11:48.885
It was a multi institutional

NOTE Confidence: 0.9325591

00:11:49.105 --> 00:11:50.625
study across con across the

NOTE Confidence: 0.9325591

00:11:50.625 --> 00:11:51.105
country,

NOTE Confidence: 0.97632456

00:11:52.260 --> 00:11:54.420
pulling, three twenty one patients

NOTE Confidence: 0.97632456

00:11:54.420 --> 00:11:55.860
for the validation cohort. It

NOTE Confidence: 0.97632456

00:11:55.860 --> 00:11:56.820
was powered to detect a

NOTE Confidence: 0.97632456

00:11:56.820 --> 00:11:58.260
hazard ratio of three year

NOTE Confidence: 0.97632456

00:11:58.260 --> 00:11:58.760
metastasis

NOTE Confidence: 0.99546385

00:11:59.620 --> 00:12:00.760
of two point one.

NOTE Confidence: 0.9779443

00:12:01.300 --> 00:12:03.300
It, included patients that were

NOTE Confidence: 0.9779443

00:12:03.300 --> 00:12:04.179
at least had at least

NOTE Confidence: 0.9779443

00:12:04.179 --> 00:12:05.300
one high risk feature, so

NOTE Confidence: 0.9779443

00:12:05.300 --> 00:12:05.960
at least

NOTE Confidence: 0.93580985

00:12:06.340 --> 00:12:06.840
BWH

NOTE Confidence: 0.9309373

00:12:07.625 --> 00:12:08.605
one, and then

NOTE Confidence: 0.96110344

00:12:09.304 --> 00:12:10.585
a slightly higher risk of

NOTE Confidence: 0.96110344

00:12:10.585 --> 00:12:12.505
metastasis rate for these patients,

NOTE Confidence: 0.96110344

00:12:12.505 --> 00:12:14.105
or rate of metastasis, sixteen

NOTE Confidence: 0.96110344

00:12:14.105 --> 00:12:15.785
point two percent, versus the

NOTE Confidence: 0.96110344

00:12:15.785 --> 00:12:17.545
general population, which ranges anywhere

NOTE Confidence: 0.96110344

00:12:17.545 --> 00:12:18.845
from two to five percent.

NOTE Confidence: 0.91062444

00:12:20.570 --> 00:12:22.009
Similar to the,

NOTE Confidence: 0.9454555

00:12:22.490 --> 00:12:24.190
survival curves that doctor Swozzi

NOTE Confidence: 0.9454555

00:12:24.250 --> 00:12:25.690
shared, you can see here

NOTE Confidence: 0.9454555

00:12:25.690 --> 00:12:26.190
that,

NOTE Confidence: 0.96112216

00:12:26.809 --> 00:12:27.309
the

NOTE Confidence: 0.8512462

00:12:27.690 --> 00:12:29.630
three year metastasis free survival,

NOTE Confidence: 0.9044973

00:12:30.649 --> 00:12:33.285
is separated out, stratified by

NOTE Confidence: 0.9044973

00:12:33.285 --> 00:12:34.885
these classes with class one

NOTE Confidence: 0.9044973

00:12:34.885 --> 00:12:36.345
a, again, the low biological

NOTE Confidence: 0.9044973

00:12:36.645 --> 00:12:37.145
risk,

NOTE Confidence: 0.9436411

00:12:37.845 --> 00:12:39.225
with a three year metastasis

NOTE Confidence: 0.9436411

00:12:39.365 --> 00:12:41.045
free survival about ninety one

NOTE Confidence: 0.9436411

00:12:41.045 --> 00:12:42.645
percent. Two a would be

NOTE Confidence: 0.9436411

00:12:42.645 --> 00:12:43.304
the moderate,

NOTE Confidence: 0.9536316

00:12:44.005 --> 00:12:45.690
moderate risk. That's about eighty

NOTE Confidence: 0.9397685

00:12:46.090 --> 00:12:47.450
percent through your survival. And

NOTE Confidence: 0.9397685

00:12:47.450 --> 00:12:48.890
2b, as we would expect

NOTE Confidence: 0.9397685

00:12:48.890 --> 00:12:50.670
with the highest risk, biological

NOTE Confidence: 0.9397685

00:12:50.730 --> 00:12:51.230
behavior,

NOTE Confidence: 0.8866689

00:12:52.010 --> 00:12:54.170
through your metastasis free survival

NOTE Confidence: 0.8866689

00:12:54.170 --> 00:12:55.470
about forty four percent.

NOTE Confidence: 0.9664243

00:12:58.135 --> 00:12:59.035
Hazard ratio,

NOTE Confidence: 0.9401262

00:12:59.415 --> 00:13:00.934
it was powered to demonstrate

NOTE Confidence: 0.9401262

00:13:00.934 --> 00:13:02.235
this and hazard ratio,

NOTE Confidence: 0.8047269

00:13:03.415 --> 00:13:04.635
for three year metastasis,

NOTE Confidence: 0.9536851

00:13:05.255 --> 00:13:07.015
for 2a was two point

NOTE Confidence: 0.9536851

00:13:07.015 --> 00:13:07.975
four four, and then it

NOTE Confidence: 0.9536851

00:13:07.975 --> 00:13:10.154
increases tenfold. So three year

NOTE Confidence: 0.96220964

00:13:10.679 --> 00:13:12.280
risk of metastasis for 2B

NOTE Confidence: 0.96220964

00:13:12.280 --> 00:13:13.420
tumors is tenfold,

NOTE Confidence: 0.9740366

00:13:13.880 --> 00:13:14.380
greater,

NOTE Confidence: 0.92493904

00:13:15.960 --> 00:13:17.400
than class I. And then

NOTE Confidence: 0.92493904

00:13:17.400 --> 00:13:19.400
the disease specific survival disease

NOTE Confidence: 0.92493904

00:13:19.400 --> 00:13:21.260
specific death also is significantly

NOTE Confidence: 0.92493904

00:13:21.480 --> 00:13:22.860
increased, for both,

NOTE Confidence: 0.97974217

00:13:23.559 --> 00:13:25.100
2A and 2B tumors.

NOTE Confidence: 0.9962405

00:13:26.345 --> 00:13:27.384
I think it's important to

NOTE Confidence: 0.9962405

00:13:27.384 --> 00:13:28.345
just look at how this

NOTE Confidence: 0.9962405

00:13:28.345 --> 00:13:29.324
tool was developed.

NOTE Confidence: 0.9651591

00:13:29.944 --> 00:13:30.665
It was,

NOTE Confidence: 0.8050045

00:13:31.944 --> 00:13:32.504
it was,

NOTE Confidence: 0.9798876

00:13:33.144 --> 00:13:33.884
deep learning,

NOTE Confidence: 0.9646565

00:13:34.504 --> 00:13:37.004
on training data that was,

NOTE Confidence: 0.92279714

00:13:37.464 --> 00:13:39.384
one hundred and twenty two

NOTE Confidence: 0.92279714

00:13:39.384 --> 00:13:39.884
patients.

NOTE Confidence: 0.9757824

00:13:40.429 --> 00:13:41.550
I think it's important to

NOTE Confidence: 0.9757824

00:13:41.550 --> 00:13:42.509
note that as you can

NOTE Confidence: 0.9757824

00:13:42.509 --> 00:13:43.250
see here,

NOTE Confidence: 0.99022025

00:13:44.750 --> 00:13:46.829
the AJCC class t three

NOTE Confidence: 0.99022025

00:13:46.829 --> 00:13:48.190
and t four tumors are

NOTE Confidence: 0.99022025

00:13:48.190 --> 00:13:49.089
quite underrepresented,

NOTE Confidence: 0.97351336

00:13:49.470 --> 00:13:51.069
specifically t four. There's one

NOTE Confidence: 0.97351336

00:13:51.069 --> 00:13:52.269
patient with a t four

NOTE Confidence: 0.97351336

00:13:52.269 --> 00:13:52.769
tumor.

NOTE Confidence: 0.97200227

00:13:53.125 --> 00:13:54.005
And I think the the

NOTE Confidence: 0.97200227

00:13:54.005 --> 00:13:55.285
same can be said for

NOTE Confidence: 0.97200227

00:13:55.285 --> 00:13:57.285
BWH staging, so a pretty

NOTE Confidence: 0.97200227

00:13:57.285 --> 00:13:58.885
small sample size for t

NOTE Confidence: 0.97200227

00:13:58.885 --> 00:14:00.165
two b and t three

NOTE Confidence: 0.97200227

00:14:00.165 --> 00:14:00.665
tumors.

NOTE Confidence: 0.9973977

00:14:01.525 --> 00:14:03.625
When they, trained their,

NOTE Confidence: 0.9929523

00:14:04.325 --> 00:14:05.065
their model,

NOTE Confidence: 0.91340566

00:14:05.525 --> 00:14:06.725
and then compared it or

NOTE Confidence: 0.91340566

00:14:06.725 --> 00:14:08.345
then validated against

NOTE Confidence: 0.951758

00:14:09.179 --> 00:14:10.860
additional cohort of three twenty

NOTE Confidence: 0.951758

00:14:10.860 --> 00:14:11.520
one patients,

NOTE Confidence: 0.89907444

00:14:12.140 --> 00:14:12.620
their,

NOTE Confidence: 0.95029753

00:14:13.100 --> 00:14:14.540
numbers of T3 and T4

NOTE Confidence: 0.95029753

00:14:14.540 --> 00:14:16.220
tumors were slightly increased, but

NOTE Confidence: 0.95029753

00:14:16.220 --> 00:14:17.580
still quite small. So just

NOTE Confidence: 0.95029753

00:14:17.580 --> 00:14:19.420
seven seven patients with T4

NOTE Confidence: 0.95029753

00:14:19.420 --> 00:14:21.580
tumors by AJCC eight and

NOTE Confidence: 0.95029753

00:14:21.580 --> 00:14:23.100
seven with T3 tumors by

NOTE Confidence: 0.95029753

00:14:23.100 --> 00:14:23.600
BWH.

NOTE Confidence: 0.96187234

00:14:24.735 --> 00:14:25.235
The,

NOTE Confidence: 0.96656257

00:14:25.695 --> 00:14:26.575
at the end of their

NOTE Confidence: 0.96656257

00:14:26.575 --> 00:14:28.015
kind of validation study, they

NOTE Confidence: 0.96656257

00:14:28.015 --> 00:14:29.214
found that about half of

NOTE Confidence: 0.96656257

00:14:29.214 --> 00:14:30.654
their patients had this class

NOTE Confidence: 0.96656257

00:14:30.654 --> 00:14:32.415
one low biologic risk. Class

NOTE Confidence: 0.96656257

00:14:32.415 --> 00:14:33.855
2a was just under half

NOTE Confidence: 0.96656257

00:14:33.855 --> 00:14:35.535
with a very small proportion

NOTE Confidence: 0.96656257

00:14:35.535 --> 00:14:36.975
being class 2b, that very

NOTE Confidence: 0.96656257

00:14:36.975 --> 00:14:37.714
high risk.

NOTE Confidence: 0.9874233

00:14:38.710 --> 00:14:39.830
I think it's also interesting

NOTE Confidence: 0.9874233

00:14:39.830 --> 00:14:40.870
to look at some of

NOTE Confidence: 0.9874233

00:14:40.870 --> 00:14:41.350
their,

NOTE Confidence: 0.99028844

00:14:41.830 --> 00:14:43.610
some of their regression data.

NOTE Confidence: 0.9831892

00:14:44.710 --> 00:14:46.650
Their data failed to show,

NOTE Confidence: 0.96974534

00:14:47.270 --> 00:14:48.090
an increased,

NOTE Confidence: 0.9613032

00:14:48.950 --> 00:14:50.150
or a hazard ratio for

NOTE Confidence: 0.9613032

00:14:50.150 --> 00:14:51.830
three year metastasis for T4

NOTE Confidence: 0.9613032

00:14:51.830 --> 00:14:52.330
tumors.

NOTE Confidence: 0.9777708

00:14:52.904 --> 00:14:53.945
You would think that by

NOTE Confidence: 0.9777708

00:14:53.945 --> 00:14:56.264
AJCC criteria T4 tumors, you

NOTE Confidence: 0.9777708

00:14:56.264 --> 00:14:57.625
would see an increased risk

NOTE Confidence: 0.9777708

00:14:57.625 --> 00:14:58.904
of three year metastasis. It

NOTE Confidence: 0.9777708

00:14:58.904 --> 00:15:00.264
just makes sense. These are

NOTE Confidence: 0.9777708

00:15:00.264 --> 00:15:02.105
advanced stage tumors, but their

NOTE Confidence: 0.9777708

00:15:02.105 --> 00:15:03.565
data is not showing this.

NOTE Confidence: 0.9463884

00:15:03.945 --> 00:15:04.904
And the same is true

NOTE Confidence: 0.9463884

00:15:04.904 --> 00:15:05.644
for the BWH

NOTE Confidence: 0.96230435

00:15:06.040 --> 00:15:07.400
staging. Their t three tumors,

NOTE Confidence: 0.96230435

00:15:07.400 --> 00:15:08.760
there's not an increase or

NOTE Confidence: 0.96230435

00:15:08.760 --> 00:15:10.280
there there's no increased kind

NOTE Confidence: 0.96230435

00:15:10.280 --> 00:15:11.880
of hazard of, three year

NOTE Confidence: 0.96230435

00:15:11.880 --> 00:15:12.380
metastasis.

NOTE Confidence: 0.94285846

00:15:13.480 --> 00:15:14.920
When they kind of change

NOTE Confidence: 0.94285846

00:15:14.920 --> 00:15:15.800
the data a little bit

NOTE Confidence: 0.94285846

00:15:15.800 --> 00:15:17.000
and combine some of these,

NOTE Confidence: 0.9593998

00:15:17.720 --> 00:15:20.195
the the staging, they combined

NOTE Confidence: 0.9593998

00:15:20.255 --> 00:15:21.215
t one and t two

NOTE Confidence: 0.9593998

00:15:21.215 --> 00:15:22.415
and then combined t three,

NOTE Confidence: 0.9593998

00:15:22.415 --> 00:15:23.775
t four, and then they

NOTE Confidence: 0.9593998

00:15:23.775 --> 00:15:24.895
did find a,

NOTE Confidence: 0.98572904

00:15:25.775 --> 00:15:27.615
an increased hazard of three

NOTE Confidence: 0.98572904

00:15:27.615 --> 00:15:28.435
year metastasis

NOTE Confidence: 0.9945339

00:15:28.815 --> 00:15:29.315
of

NOTE Confidence: 0.8284087

00:15:29.695 --> 00:15:30.195
two,

NOTE Confidence: 0.8794593

00:15:31.379 --> 00:15:31.860
with,

NOTE Confidence: 0.9247074

00:15:32.259 --> 00:15:33.699
class 2b having a near

NOTE Confidence: 0.9247074

00:15:33.699 --> 00:15:34.199
tenfold,

NOTE Confidence: 0.9894474

00:15:35.139 --> 00:15:36.420
increased risk of three year

NOTE Confidence: 0.9894474

00:15:36.420 --> 00:15:36.920
metastasis.

NOTE Confidence: 0.96216786

00:15:37.860 --> 00:15:39.060
But important to note that

NOTE Confidence: 0.96216786

00:15:39.060 --> 00:15:40.600
advanced stage tumors are underrepresented

NOTE Confidence: 0.96216786

00:15:40.819 --> 00:15:42.180
in this validation study. So

NOTE Confidence: 0.96216786

00:15:42.180 --> 00:15:43.379
what raises the question of,

NOTE Confidence: 0.96216786

00:15:43.379 --> 00:15:44.894
is this a useful tool

NOTE Confidence: 0.96216786

00:15:44.894 --> 00:15:46.675
for these advanced stage tumors,

NOTE Confidence: 0.9325207

00:15:47.535 --> 00:15:49.795
T3, T4 by AJCC criteria.

NOTE Confidence: 0.99685955

00:15:50.894 --> 00:15:52.574
Efforts to look at all

NOTE Confidence: 0.99685955

00:15:52.574 --> 00:15:53.634
the available literature,

NOTE Confidence: 0.9561953

00:15:54.095 --> 00:15:55.295
have been made of meta

NOTE Confidence: 0.9561953

00:15:55.295 --> 00:15:57.375
analysis and systematic review, looked

NOTE Confidence: 0.9561953

00:15:57.375 --> 00:15:58.274
at all available,

NOTE Confidence: 0.92856747

00:15:59.700 --> 00:16:00.900
research at the time. This

NOTE Confidence: 0.92856747

00:16:00.900 --> 00:16:01.780
was a twenty twenty three

NOTE Confidence: 0.92856747

00:16:01.780 --> 00:16:04.020
meta analysis, and they were

NOTE Confidence: 0.92856747

00:16:04.020 --> 00:16:06.100
after they, looked through all

NOTE Confidence: 0.92856747

00:16:06.100 --> 00:16:08.340
available studies, they, found three

NOTE Confidence: 0.92856747

00:16:08.340 --> 00:16:09.700
studies that reached that met

NOTE Confidence: 0.92856747

00:16:09.700 --> 00:16:11.780
inclusion criteria representing just over

NOTE Confidence: 0.92856747

00:16:11.780 --> 00:16:12.705
a thousand patients.

NOTE Confidence: 0.98218846

00:16:13.265 --> 00:16:14.625
They did find similar three

NOTE Confidence: 0.98218846

00:16:14.625 --> 00:16:16.945
year metastasis free survival across

NOTE Confidence: 0.98218846

00:16:16.945 --> 00:16:18.245
classes, where

NOTE Confidence: 0.9031069

00:16:18.625 --> 00:16:19.825
similar to the data I

NOTE Confidence: 0.9031069

00:16:19.825 --> 00:16:21.265
presented earlier and what Doctor.

NOTE Confidence: 0.9031069

00:16:21.265 --> 00:16:22.325
Swozzi presented,

NOTE Confidence: 0.9121022

00:16:22.705 --> 00:16:24.945
class I anywhere from ninety

NOTE Confidence: 0.9121022

00:16:24.945 --> 00:16:25.825
one percent to ninety three

NOTE Confidence: 0.9121022

00:16:25.825 --> 00:16:27.825
percent, three year metastasis free

NOTE Confidence: 0.9121022

00:16:27.825 --> 00:16:28.325
survival.

NOTE Confidence: 0.97046936

00:16:28.680 --> 00:16:29.800
Two a is slightly worse

NOTE Confidence: 0.97046936

00:16:29.800 --> 00:16:31.000
at seventy six to eighty

NOTE Confidence: 0.97046936

00:16:31.000 --> 00:16:32.300
percent. And two b,

NOTE Confidence: 0.9763922

00:16:32.920 --> 00:16:34.120
the worst of the of

NOTE Confidence: 0.9763922

00:16:34.120 --> 00:16:35.320
the three with forty three

NOTE Confidence: 0.9763922

00:16:35.320 --> 00:16:36.540
to forty seven percent

NOTE Confidence: 0.9423562

00:16:37.000 --> 00:16:38.940
three year metastasis free survival.

NOTE Confidence: 0.9803099

00:16:40.520 --> 00:16:42.700
Looking at positive predictive value

NOTE Confidence: 0.9803099

00:16:42.920 --> 00:16:44.140
of the forty GEP,

NOTE Confidence: 0.95419776

00:16:44.895 --> 00:16:46.435
is actually a fairly,

NOTE Confidence: 0.982347

00:16:47.135 --> 00:16:49.375
substantial positive predictive value, about

NOTE Confidence: 0.982347

00:16:49.375 --> 00:16:50.435
fifty five percent,

NOTE Confidence: 0.861111

00:16:50.895 --> 00:16:52.115
for class 2b

NOTE Confidence: 0.9383763

00:16:52.575 --> 00:16:54.175
when compared to class one

NOTE Confidence: 0.9383763

00:16:54.175 --> 00:16:55.315
and class 2a.

NOTE Confidence: 0.99859047

00:16:55.935 --> 00:16:57.215
And when you compare that

NOTE Confidence: 0.99859047

00:16:57.215 --> 00:16:58.575
to the positive predictive value

NOTE Confidence: 0.99859047

00:16:58.575 --> 00:16:59.395
of AJCC

NOTE Confidence: 0.95673966

00:17:00.140 --> 00:17:00.960
and BWH,

NOTE Confidence: 0.99256295

00:17:02.060 --> 00:17:04.060
the forty gene panel is

NOTE Confidence: 0.99256295

00:17:04.060 --> 00:17:05.740
higher. So the positive predictive

NOTE Confidence: 0.99256295

00:17:05.740 --> 00:17:07.580
value for AJCC was just

NOTE Confidence: 0.99256295

00:17:07.580 --> 00:17:08.540
about a third, thirty three

NOTE Confidence: 0.99256295

00:17:08.540 --> 00:17:10.300
percent, and for the Brigham

NOTE Confidence: 0.99256295

00:17:10.300 --> 00:17:11.820
and Women's, thirty six percent.

NOTE Confidence: 0.99256295

00:17:11.820 --> 00:17:12.320
So

NOTE Confidence: 0.98022485

00:17:12.675 --> 00:17:14.595
the positive predictive value for

NOTE Confidence: 0.98022485

00:17:14.595 --> 00:17:16.855
the forty gene, expression profiling

NOTE Confidence: 0.98022485

00:17:16.915 --> 00:17:19.575
test is does outperform AJCC

NOTE Confidence: 0.98022485

00:17:19.875 --> 00:17:20.615
and BWH.

NOTE Confidence: 0.9988534

00:17:22.195 --> 00:17:23.555
To look specifically at head

NOTE Confidence: 0.9988534

00:17:23.555 --> 00:17:24.035
and neck,

NOTE Confidence: 0.9822498

00:17:24.835 --> 00:17:26.275
a subset of the original

NOTE Confidence: 0.9822498

00:17:26.275 --> 00:17:28.135
validation cohort was analyzed.

NOTE Confidence: 0.704504

00:17:28.740 --> 00:17:29.800
Similar researchers,

NOTE Confidence: 0.9593079

00:17:30.260 --> 00:17:31.300
on this study as well,

NOTE Confidence: 0.9593079

00:17:31.300 --> 00:17:32.580
but looking specifically at the

NOTE Confidence: 0.9593079

00:17:32.580 --> 00:17:33.400
head and neck.

NOTE Confidence: 0.90761346

00:17:34.100 --> 00:17:36.100
Similar Kaplan Meier curves for

NOTE Confidence: 0.90761346

00:17:36.100 --> 00:17:37.540
these with class I three

NOTE Confidence: 0.90761346

00:17:37.540 --> 00:17:39.380
year metastasis free survival ninety

NOTE Confidence: 0.90761346

00:17:39.380 --> 00:17:40.260
two percent. You can see

NOTE Confidence: 0.90761346

00:17:40.260 --> 00:17:41.619
the numbers here, seventy six

NOTE Confidence: 0.90761346

00:17:41.619 --> 00:17:43.140
for class IIa, forty four

NOTE Confidence: 0.90761346

00:17:43.140 --> 00:17:44.165
for class two b. So

NOTE Confidence: 0.90761346

00:17:44.165 --> 00:17:45.225
very similar to,

NOTE Confidence: 0.9758136

00:17:46.085 --> 00:17:46.965
looking at,

NOTE Confidence: 0.99706155

00:17:47.365 --> 00:17:48.885
squamous cell carcinomas of the

NOTE Confidence: 0.99706155

00:17:48.885 --> 00:17:50.325
entire body, when you look

NOTE Confidence: 0.99706155

00:17:50.325 --> 00:17:51.045
at this for head and

NOTE Confidence: 0.99706155

00:17:51.045 --> 00:17:51.705
neck cancers.

NOTE Confidence: 0.99322355

00:17:54.244 --> 00:17:56.345
The sites represented here,

NOTE Confidence: 0.9834457

00:17:57.045 --> 00:17:59.190
where lip and scalp actually

NOTE Confidence: 0.9834457

00:17:59.190 --> 00:18:00.230
had the highest rates of

NOTE Confidence: 0.9834457

00:18:00.230 --> 00:18:00.730
metastasis.

NOTE Confidence: 0.99956095

00:18:01.270 --> 00:18:02.650
The most common locations

NOTE Confidence: 0.96107227

00:18:03.109 --> 00:18:05.510
were the, ears, cheeks, and

NOTE Confidence: 0.96107227

00:18:05.510 --> 00:18:06.010
scalp.

NOTE Confidence: 0.97279257

00:18:06.869 --> 00:18:08.309
But when they looked at

NOTE Confidence: 0.97279257

00:18:08.309 --> 00:18:10.070
metastasis rate by location on

NOTE Confidence: 0.97279257

00:18:10.070 --> 00:18:11.030
the head and neck, there

NOTE Confidence: 0.97279257

00:18:11.109 --> 00:18:12.630
they found no difference, in

NOTE Confidence: 0.97279257

00:18:12.630 --> 00:18:14.375
metastatic events and,

NOTE Confidence: 0.998733

00:18:15.014 --> 00:18:16.054
location of the head and

NOTE Confidence: 0.998733

00:18:16.054 --> 00:18:16.554
neck.

NOTE Confidence: 0.9677092

00:18:17.815 --> 00:18:18.695
And then here you can

NOTE Confidence: 0.9677092

00:18:18.695 --> 00:18:20.054
see here again depicted the

NOTE Confidence: 0.9677092

00:18:20.215 --> 00:18:21.575
this is it's very similar

NOTE Confidence: 0.9677092

00:18:21.575 --> 00:18:23.095
to what, what I presented

NOTE Confidence: 0.9677092

00:18:23.095 --> 00:18:24.615
with the validation study. This

NOTE Confidence: 0.9677092

00:18:24.695 --> 00:18:26.375
when you extrapolate out or,

NOTE Confidence: 0.9514263

00:18:26.980 --> 00:18:28.019
analyze the head and neck

NOTE Confidence: 0.9514263

00:18:28.019 --> 00:18:29.139
patients, the say it's a

NOTE Confidence: 0.9514263

00:18:29.139 --> 00:18:30.580
similar positive predictive value of

NOTE Confidence: 0.9514263

00:18:30.580 --> 00:18:31.960
about fifty five percent,

NOTE Confidence: 0.9092332

00:18:32.899 --> 00:18:34.500
higher than the positive predictive

NOTE Confidence: 0.9092332

00:18:34.500 --> 00:18:35.460
value. And that's for the

NOTE Confidence: 0.9092332

00:18:35.460 --> 00:18:36.600
for the for the gene,

NOTE Confidence: 0.9846444

00:18:37.139 --> 00:18:39.375
gene expression profiling test, fifty

NOTE Confidence: 0.9846444

00:18:39.375 --> 00:18:41.395
five percent positive predictive value

NOTE Confidence: 0.95382184

00:18:41.935 --> 00:18:43.455
compared to just thirty seven

NOTE Confidence: 0.95382184

00:18:43.455 --> 00:18:44.515
percent for AJCC

NOTE Confidence: 0.9536325

00:18:44.815 --> 00:18:46.494
eighth edition for advanced stage

NOTE Confidence: 0.9536325

00:18:46.494 --> 00:18:47.875
tumors and the BWH,

NOTE Confidence: 0.9857461

00:18:48.655 --> 00:18:50.095
advanced stage tumors. So, again,

NOTE Confidence: 0.9857461

00:18:50.095 --> 00:18:51.775
it outperforms those two for

NOTE Confidence: 0.9857461

00:18:51.775 --> 00:18:53.155
the positive predictive value.

NOTE Confidence: 0.93366146

00:18:55.270 --> 00:18:57.109
So like the AJCC eighth

NOTE Confidence: 0.93366146

00:18:57.109 --> 00:18:58.730
edition and Brigham women's

NOTE Confidence: 0.9529064

00:18:59.030 --> 00:19:00.869
staging system, the forty gene,

NOTE Confidence: 0.9529064

00:19:01.270 --> 00:19:03.990
expression profile testing does class

NOTE Confidence: 0.9529064

00:19:04.150 --> 00:19:05.590
or it classified lower rates

NOTE Confidence: 0.9529064

00:19:05.590 --> 00:19:06.790
of tumor as high risk

NOTE Confidence: 0.9529064

00:19:06.790 --> 00:19:08.090
compared to the NCCN.

NOTE Confidence: 0.90139794

00:19:08.595 --> 00:19:10.034
As doctor Suozzi showed,

NOTE Confidence: 0.9999223

00:19:10.434 --> 00:19:10.934
NCCN

NOTE Confidence: 0.98940605

00:19:11.794 --> 00:19:13.475
breaks patients down by low,

NOTE Confidence: 0.98940605

00:19:13.475 --> 00:19:14.775
high, and very high.

NOTE Confidence: 0.99574214

00:19:15.155 --> 00:19:16.855
And just by definition,

NOTE Confidence: 0.9343643

00:19:18.195 --> 00:19:19.554
head and neck is high

NOTE Confidence: 0.9343643

00:19:19.554 --> 00:19:20.054
risk.

NOTE Confidence: 0.9962307

00:19:20.434 --> 00:19:22.560
And so this test actually

NOTE Confidence: 0.96162295

00:19:22.860 --> 00:19:23.920
kind of downstages,

NOTE Confidence: 0.97987705

00:19:24.940 --> 00:19:25.440
downgrades,

NOTE Confidence: 0.99694973

00:19:26.460 --> 00:19:27.500
patients of the head and

NOTE Confidence: 0.99694973

00:19:27.500 --> 00:19:28.000
neck,

NOTE Confidence: 0.98116565

00:19:28.300 --> 00:19:29.280
whereas the NCCN,

NOTE Confidence: 0.9997581

00:19:29.900 --> 00:19:31.040
would not do that.

NOTE Confidence: 0.94827366

00:19:31.420 --> 00:19:32.460
And then when they compared

NOTE Confidence: 0.94827366

00:19:32.460 --> 00:19:33.820
these the head and neck

NOTE Confidence: 0.94827366

00:19:33.820 --> 00:19:34.320
sites,

NOTE Confidence: 0.98275197

00:19:35.804 --> 00:19:36.244
to,

NOTE Confidence: 0.9855919

00:19:36.684 --> 00:19:38.284
cancers of all sites of

NOTE Confidence: 0.9855919

00:19:38.284 --> 00:19:39.484
the body, they found that

NOTE Confidence: 0.9855919

00:19:39.484 --> 00:19:40.845
a higher percentage of cases

NOTE Confidence: 0.9855919

00:19:40.845 --> 00:19:42.205
were at moderate risk, so

NOTE Confidence: 0.9855919

00:19:42.205 --> 00:19:42.865
at 2a,

NOTE Confidence: 0.9802769

00:19:43.325 --> 00:19:44.605
and that a lower percent

NOTE Confidence: 0.9802769

00:19:44.605 --> 00:19:46.524
was at, the low risk

NOTE Confidence: 0.9802769

00:19:46.524 --> 00:19:47.904
of of class one,

NOTE Confidence: 0.93142265

00:19:48.640 --> 00:19:49.760
implying a sort of shift

NOTE Confidence: 0.93142265

00:19:49.760 --> 00:19:50.800
to higher risk for head

NOTE Confidence: 0.93142265

00:19:50.800 --> 00:19:52.580
and neck region, which we

NOTE Confidence: 0.90685403

00:19:52.960 --> 00:19:54.100
know that to be true.

NOTE Confidence: 0.9726946

00:19:54.880 --> 00:19:56.340
So I'm just gonna demonstrate

NOTE Confidence: 0.9726946

00:19:56.560 --> 00:19:57.520
kind of the impact that

NOTE Confidence: 0.9726946

00:19:57.520 --> 00:19:59.040
this could have in some

NOTE Confidence: 0.9726946

00:19:59.040 --> 00:20:00.640
clinical scenarios. So these are

NOTE Confidence: 0.9726946

00:20:00.640 --> 00:20:01.680
case studies that,

NOTE Confidence: 0.98204076

00:20:03.325 --> 00:20:04.685
two cases from a case

NOTE Confidence: 0.98204076

00:20:04.685 --> 00:20:06.285
series published in two thousand

NOTE Confidence: 0.98204076

00:20:06.285 --> 00:20:08.125
and two, two very similar

NOTE Confidence: 0.98204076

00:20:08.125 --> 00:20:09.805
patients from just kind of

NOTE Confidence: 0.98204076

00:20:09.805 --> 00:20:10.465
their history.

NOTE Confidence: 0.9881218

00:20:11.005 --> 00:20:11.805
So the first is a

NOTE Confidence: 0.9881218

00:20:11.805 --> 00:20:13.105
sixty five year old male

NOTE Confidence: 0.9881218

00:20:13.325 --> 00:20:14.625
with a double transplant,

NOTE Confidence: 0.932345

00:20:15.405 --> 00:20:17.085
with, who developed this sort

NOTE Confidence: 0.932345

00:20:17.085 --> 00:20:18.220
of small one point three

NOTE Confidence: 0.932345

00:20:18.220 --> 00:20:20.159
centimeter papule on the temple.

NOTE Confidence: 0.93700796

00:20:20.460 --> 00:20:21.980
By AJCC, it's a stage

NOTE Confidence: 0.93700796

00:20:21.980 --> 00:20:23.419
one. BWH, it was a

NOTE Confidence: 0.93700796

00:20:23.419 --> 00:20:24.480
stage two a.

NOTE Confidence: 0.94243693

00:20:25.580 --> 00:20:27.919
He underwent Moe's, surgery,

NOTE Confidence: 0.9975921

00:20:28.380 --> 00:20:29.359
several stages.

NOTE Confidence: 0.9014686

00:20:30.380 --> 00:20:32.355
There was a an initial,

NOTE Confidence: 0.99343896

00:20:32.734 --> 00:20:34.255
initially, all margins were determined

NOTE Confidence: 0.99343896

00:20:34.255 --> 00:20:35.135
to be negative, but a

NOTE Confidence: 0.99343896

00:20:35.135 --> 00:20:36.895
subsequent analysis showed a small

NOTE Confidence: 0.99343896

00:20:36.895 --> 00:20:38.034
focus of,

NOTE Confidence: 0.99621266

00:20:38.734 --> 00:20:39.934
of cancer remaining in the

NOTE Confidence: 0.99621266

00:20:39.934 --> 00:20:42.115
tumor bed. Patient was notified,

NOTE Confidence: 0.97195804

00:20:42.975 --> 00:20:44.975
discussed additional treatment with radiation

NOTE Confidence: 0.97195804

00:20:44.975 --> 00:20:46.434
oncology. He declined.

NOTE Confidence: 0.9780204

00:20:47.160 --> 00:20:47.600
And,

NOTE Confidence: 0.9767912

00:20:48.040 --> 00:20:49.100
at the time of follow-up,

NOTE Confidence: 0.9767912

00:20:49.320 --> 00:20:49.800
he,

NOTE Confidence: 0.99988157

00:20:50.359 --> 00:20:51.580
was without disease.

NOTE Confidence: 0.9887611

00:20:52.359 --> 00:20:53.720
They tested his tumor, and

NOTE Confidence: 0.9887611

00:20:53.720 --> 00:20:55.020
it was a class one,

NOTE Confidence: 0.97834986

00:20:55.720 --> 00:20:57.100
for the forty GEP.

NOTE Confidence: 0.98664576

00:20:58.600 --> 00:20:59.880
A very similar patient, a

NOTE Confidence: 0.98664576

00:20:59.880 --> 00:21:00.920
sixty nine year old male,

NOTE Confidence: 0.98664576

00:21:00.920 --> 00:21:02.845
also liver transplant, several month

NOTE Confidence: 0.98664576

00:21:02.845 --> 00:21:04.684
history of a similar size

NOTE Confidence: 0.98664576

00:21:04.684 --> 00:21:06.225
lesion in a similar location.

NOTE Confidence: 0.9725725

00:21:06.924 --> 00:21:07.984
This one's exophytic,

NOTE Confidence: 0.9419397

00:21:08.525 --> 00:21:10.205
in its appearance, but similar

NOTE Confidence: 0.9419397

00:21:10.205 --> 00:21:12.285
staging, AJCC eighth edition one

NOTE Confidence: 0.9419397

00:21:12.285 --> 00:21:13.265
and then the BWH

NOTE Confidence: 0.99606925

00:21:13.580 --> 00:21:14.480
t two a.

NOTE Confidence: 0.99092853

00:21:14.940 --> 00:21:16.320
So this patient underwent,

NOTE Confidence: 0.9130427

00:21:16.780 --> 00:21:19.200
Mohs micrographic surgery, two stages,

NOTE Confidence: 0.86542386

00:21:19.740 --> 00:21:20.960
margins were clear,

NOTE Confidence: 0.9990164

00:21:21.820 --> 00:21:24.060
very short interval recurrence at

NOTE Confidence: 0.9990164

00:21:24.060 --> 00:21:25.040
about four months.

NOTE Confidence: 0.8795328

00:21:26.955 --> 00:21:29.935
He consulted with, radiation oncology.

NOTE Confidence: 0.8795328

00:21:30.075 --> 00:21:30.815
He received

NOTE Confidence: 0.87654144

00:21:31.435 --> 00:21:32.795
he received radiation to the

NOTE Confidence: 0.87654144

00:21:32.795 --> 00:21:33.295
temple.

NOTE Confidence: 0.9823289

00:21:34.155 --> 00:21:35.855
He developed cervical lymphadenopathy,

NOTE Confidence: 0.75472707

00:21:37.275 --> 00:21:37.775
and,

NOTE Confidence: 0.9752605

00:21:39.220 --> 00:21:41.060
which was positive for squamous

NOTE Confidence: 0.9752605

00:21:41.060 --> 00:21:42.280
cell carcinoma metastasis.

NOTE Confidence: 0.9812263

00:21:43.620 --> 00:21:45.220
He, rather than having surgery,

NOTE Confidence: 0.9812263

00:21:45.220 --> 00:21:46.500
he underwent radiation to the

NOTE Confidence: 0.9812263

00:21:46.500 --> 00:21:47.000
neck.

NOTE Confidence: 0.947323

00:21:47.380 --> 00:21:48.360
He then developed,

NOTE Confidence: 0.91038465

00:21:49.380 --> 00:21:50.600
mediastinal metastasis,

NOTE Confidence: 0.9597456

00:21:51.715 --> 00:21:53.955
ultimately was started on it

NOTE Confidence: 0.9597456

00:21:53.955 --> 00:21:55.715
was given targeted radiation to

NOTE Confidence: 0.9597456

00:21:55.715 --> 00:21:56.294
the lung,

NOTE Confidence: 0.9681398

00:21:56.835 --> 00:21:58.595
was trialed on some systemic

NOTE Confidence: 0.9681398

00:21:58.595 --> 00:21:59.955
therapy, but he progressed through

NOTE Confidence: 0.9681398

00:21:59.955 --> 00:22:00.455
disease,

NOTE Confidence: 0.9644808

00:22:01.234 --> 00:22:02.135
and then ultimately,

NOTE Confidence: 0.96253633

00:22:02.674 --> 00:22:03.975
succumbed to his disease.

NOTE Confidence: 0.98435867

00:22:04.940 --> 00:22:06.780
Testing of his tumor revealed

NOTE Confidence: 0.98435867

00:22:06.780 --> 00:22:07.840
class two b.

NOTE Confidence: 0.9948007

00:22:08.140 --> 00:22:10.080
So two very similar appearing,

NOTE Confidence: 0.98744035

00:22:10.619 --> 00:22:11.840
kind of presentations,

NOTE Confidence: 0.9838923

00:22:12.300 --> 00:22:13.740
but the biology of these

NOTE Confidence: 0.9838923

00:22:13.740 --> 00:22:15.840
tumors are dramatically different,

NOTE Confidence: 0.99951017

00:22:16.140 --> 00:22:17.520
and that does get detected

NOTE Confidence: 0.9659501

00:22:17.820 --> 00:22:19.740
on this forty, gene expression

NOTE Confidence: 0.9659501

00:22:19.740 --> 00:22:20.115
profile

NOTE Confidence: 0.99724925

00:22:20.994 --> 00:22:22.195
test. So ways that we

NOTE Confidence: 0.99724925

00:22:22.195 --> 00:22:23.795
can utilize this,

NOTE Confidence: 0.91284704

00:22:24.275 --> 00:22:25.875
for t or 2a and

NOTE Confidence: 0.91284704

00:22:25.875 --> 00:22:26.775
2b tumors,

NOTE Confidence: 0.9904629

00:22:27.395 --> 00:22:28.675
would be to consider additional

NOTE Confidence: 0.9904629

00:22:28.675 --> 00:22:30.035
workup to evaluate the nodal

NOTE Confidence: 0.9904629

00:22:30.035 --> 00:22:30.515
basin,

NOTE Confidence: 0.84804195

00:22:30.994 --> 00:22:32.295
CT NET with contrast.

NOTE Confidence: 0.9442748

00:22:32.990 --> 00:22:34.430
You could con also, if

NOTE Confidence: 0.9442748

00:22:34.430 --> 00:22:35.470
you're having any issues with

NOTE Confidence: 0.9442748

00:22:35.470 --> 00:22:36.430
insurance, you could start with

NOTE Confidence: 0.9442748

00:22:36.430 --> 00:22:37.170
an ultrasound,

NOTE Confidence: 0.90649295

00:22:38.270 --> 00:22:39.390
and then assessing the nodal

NOTE Confidence: 0.90649295

00:22:39.390 --> 00:22:40.590
basin with a lymph node

NOTE Confidence: 0.90649295

00:22:40.590 --> 00:22:42.210
biopsy if there is lymphadenopathy

NOTE Confidence: 0.89012706

00:22:42.590 --> 00:22:44.450
just proceeding with, neck dissection.

NOTE Confidence: 0.89005613

00:22:45.494 --> 00:22:46.234
Also, potentially

NOTE Confidence: 0.85560155

00:22:46.615 --> 00:22:47.595
a role for,

NOTE Confidence: 0.997488

00:22:48.455 --> 00:22:50.155
adjuvant treatment decision making,

NOTE Confidence: 0.9468825

00:22:50.695 --> 00:22:52.855
such as radiation therapy, and

NOTE Confidence: 0.9468825

00:22:52.855 --> 00:22:53.355
doctor,

NOTE Confidence: 0.9700164

00:22:53.975 --> 00:22:55.175
Young will speak about that,

NOTE Confidence: 0.9700164

00:22:55.175 --> 00:22:56.535
and doctor Tran will speak

NOTE Confidence: 0.9700164

00:22:56.535 --> 00:22:57.355
about chemotherapy.

NOTE Confidence: 0.9436596

00:22:58.880 --> 00:23:00.340
And then also the frequency

NOTE Confidence: 0.9436596

00:23:00.399 --> 00:23:01.779
of follow-up for these patients

NOTE Confidence: 0.9436596

00:23:01.840 --> 00:23:03.600
could be increased based on

NOTE Confidence: 0.9436596

00:23:03.600 --> 00:23:04.480
their their,

NOTE Confidence: 0.9884505

00:23:04.880 --> 00:23:06.880
forty GEP results. So an

NOTE Confidence: 0.9884505

00:23:06.880 --> 00:23:08.399
example would be to escalate

NOTE Confidence: 0.9884505

00:23:08.399 --> 00:23:09.519
the care for a high

NOTE Confidence: 0.9884505

00:23:09.519 --> 00:23:10.000
risk,

NOTE Confidence: 0.9151902

00:23:10.480 --> 00:23:12.565
GEP even if the AJCC

NOTE Confidence: 0.9151902

00:23:12.625 --> 00:23:13.744
eighth edition has them as

NOTE Confidence: 0.9151902

00:23:13.744 --> 00:23:14.945
a as a t one.

NOTE Confidence: 0.9151902

00:23:14.945 --> 00:23:15.684
And similarly,

NOTE Confidence: 0.98425996

00:23:15.984 --> 00:23:17.424
consider de escalation. I would

NOTE Confidence: 0.98425996

00:23:17.424 --> 00:23:18.304
do that in the context

NOTE Confidence: 0.98425996

00:23:18.304 --> 00:23:19.125
of a multidisciplinary

NOTE Confidence: 0.9767643

00:23:19.505 --> 00:23:20.005
group,

NOTE Confidence: 0.91733044

00:23:20.385 --> 00:23:21.505
the care for low risk

NOTE Confidence: 0.91733044

00:23:21.505 --> 00:23:22.865
GEP even if it was

NOTE Confidence: 0.91733044

00:23:22.865 --> 00:23:24.085
a, like, a t three.

NOTE Confidence: 0.96997416

00:23:24.769 --> 00:23:26.710
So takeaway points from this,

NOTE Confidence: 0.98247784

00:23:27.250 --> 00:23:29.190
this was this, gene,

NOTE Confidence: 0.96761084

00:23:29.649 --> 00:23:32.470
forty, GEP test was validated,

NOTE Confidence: 0.829768

00:23:34.289 --> 00:23:34.789
retrospectively.

NOTE Confidence: 0.99069786

00:23:35.250 --> 00:23:36.450
And I would say with,

NOTE Confidence: 0.99069786

00:23:36.850 --> 00:23:38.630
some advanced stage tumors underrepresented,

NOTE Confidence: 0.98300743

00:23:39.645 --> 00:23:41.565
further prospective studies are certainly

NOTE Confidence: 0.98300743

00:23:41.565 --> 00:23:42.765
needed for us to have

NOTE Confidence: 0.98300743

00:23:42.765 --> 00:23:43.885
a better handle on how

NOTE Confidence: 0.98300743

00:23:43.885 --> 00:23:45.805
this can impact, future treatment

NOTE Confidence: 0.98300743

00:23:45.805 --> 00:23:46.865
and patient outcomes.

NOTE Confidence: 0.9828138

00:23:47.965 --> 00:23:48.765
There is a role, I

NOTE Confidence: 0.9828138

00:23:48.765 --> 00:23:49.965
think, for using it as

NOTE Confidence: 0.9828138

00:23:49.965 --> 00:23:51.085
an adjunct to our current

NOTE Confidence: 0.9828138

00:23:51.085 --> 00:23:52.590
guidelines, but not to replace

NOTE Confidence: 0.9828138

00:23:52.590 --> 00:23:53.630
them and to have it

NOTE Confidence: 0.9828138

00:23:53.630 --> 00:23:54.690
be part of a multidisciplinary,

NOTE Confidence: 0.97984695

00:23:55.549 --> 00:23:56.049
discussion.

NOTE Confidence: 0.91100985

00:23:57.150 --> 00:23:58.429
And again, used could be

NOTE Confidence: 0.91100985

00:23:58.429 --> 00:23:59.869
used to escalate care. So

NOTE Confidence: 0.91100985

00:23:59.869 --> 00:24:01.570
that first case presentation,

NOTE Confidence: 0.9641589

00:24:02.029 --> 00:24:03.150
perhaps that I'm sorry, the

NOTE Confidence: 0.9641589

00:24:03.150 --> 00:24:04.510
second case presentation where he

NOTE Confidence: 0.9641589

00:24:04.510 --> 00:24:05.570
had a rapid recurrence,

NOTE Confidence: 0.9959372

00:24:06.145 --> 00:24:07.665
perhaps he's somebody that could

NOTE Confidence: 0.9959372

00:24:07.665 --> 00:24:09.285
have gone quickly to radiation,

NOTE Confidence: 0.9500813

00:24:10.865 --> 00:24:11.365
to,

NOTE Confidence: 0.9849043

00:24:11.984 --> 00:24:13.345
as a response to that

NOTE Confidence: 0.9849043

00:24:13.345 --> 00:24:13.845
T2,

NOTE Confidence: 0.8867686

00:24:14.625 --> 00:24:16.705
or the the 2b class

NOTE Confidence: 0.8867686

00:24:16.705 --> 00:24:18.005
from the forty GEP.

NOTE Confidence: 0.9822885

00:24:18.910 --> 00:24:19.790
And I think it's also

NOTE Confidence: 0.9822885

00:24:19.790 --> 00:24:20.830
important to note that,

NOTE Confidence: 0.9559564

00:24:21.550 --> 00:24:22.990
of the studies included here

NOTE Confidence: 0.9559564

00:24:22.990 --> 00:24:23.950
and a majority of the

NOTE Confidence: 0.9559564

00:24:23.950 --> 00:24:25.250
ones that have been published,

NOTE Confidence: 0.9559564

00:24:25.310 --> 00:24:27.250
they are, industry funded,

NOTE Confidence: 0.97317386

00:24:28.030 --> 00:24:28.910
in some way. So I

NOTE Confidence: 0.97317386

00:24:28.910 --> 00:24:30.270
think it's just important to

NOTE Confidence: 0.97317386

00:24:30.270 --> 00:24:31.470
to keep it to to

NOTE Confidence: 0.97317386

00:24:31.470 --> 00:24:32.965
keep that in mind as

NOTE Confidence: 0.97317386

00:24:32.965 --> 00:24:35.284
we continue to determine the

NOTE Confidence: 0.97317386

00:24:35.284 --> 00:24:36.825
usability of these tests.

NOTE Confidence: 0.9983138

00:24:37.764 --> 00:24:38.504
Thank you.

NOTE Confidence: 0.98889464

00:24:42.965 --> 00:24:44.984
Alright. Thank you, Ansley. I'm

NOTE Confidence: 0.9913781

00:24:45.740 --> 00:24:47.180
going to go ahead and

NOTE Confidence: 0.9913781

00:24:47.180 --> 00:24:49.520
present the, radiation oncologist

NOTE Confidence: 0.96237576

00:24:50.060 --> 00:24:50.560
perspective

NOTE Confidence: 0.98681974

00:24:50.940 --> 00:24:51.420
on,

NOTE Confidence: 0.99297667

00:24:51.980 --> 00:24:53.680
our approaches to cutaneous,

NOTE Confidence: 0.79648113

00:24:54.540 --> 00:24:55.040
squain.

NOTE Confidence: 0.97085655

00:24:56.859 --> 00:24:57.740
Let me just get these

NOTE Confidence: 0.97085655

00:24:57.740 --> 00:24:58.640
slides going.

NOTE Confidence: 0.99748623

00:25:00.345 --> 00:25:00.845
Alright.

NOTE Confidence: 0.9967283

00:25:01.385 --> 00:25:01.785
So,

NOTE Confidence: 0.9705742

00:25:02.185 --> 00:25:04.185
I'm Melissa Young. I'm, the

NOTE Confidence: 0.9705742

00:25:04.185 --> 00:25:05.865
radiation oncologist on the panel

NOTE Confidence: 0.9705742

00:25:05.865 --> 00:25:06.365
today,

NOTE Confidence: 0.9926453

00:25:06.905 --> 00:25:08.105
one of the specialists in

NOTE Confidence: 0.9926453

00:25:08.105 --> 00:25:08.265
our,

NOTE Confidence: 0.86285526

00:25:09.225 --> 00:25:10.105
head and neck,

NOTE Confidence: 0.8809831

00:25:11.225 --> 00:25:13.065
department within the the department

NOTE Confidence: 0.8809831

00:25:13.065 --> 00:25:14.125
of radiation oncology.

NOTE Confidence: 0.9506055

00:25:14.539 --> 00:25:15.419
And I just want really

NOTE Confidence: 0.9506055

00:25:15.419 --> 00:25:17.760
wanted to focus specifically on,

NOTE Confidence: 0.99846524

00:25:18.779 --> 00:25:19.760
you know, how

NOTE Confidence: 0.9922796

00:25:20.140 --> 00:25:21.179
how we look at these

NOTE Confidence: 0.9922796

00:25:21.179 --> 00:25:22.380
high risk skin cancers and

NOTE Confidence: 0.9922796

00:25:22.380 --> 00:25:23.100
how we have to think

NOTE Confidence: 0.9922796

00:25:23.100 --> 00:25:24.380
about the use of adjuvant

NOTE Confidence: 0.9922796

00:25:24.380 --> 00:25:24.880
radiotherapy

NOTE Confidence: 0.9874798

00:25:25.260 --> 00:25:26.700
as a risk reductive strategy

NOTE Confidence: 0.9874798

00:25:26.700 --> 00:25:27.740
to to reduce risk of

NOTE Confidence: 0.9874798

00:25:27.740 --> 00:25:28.240
recurrence.

NOTE Confidence: 0.9621108

00:25:28.625 --> 00:25:30.085
We've already heard the data

NOTE Confidence: 0.9621108

00:25:30.225 --> 00:25:31.744
indicating that these high risk,

NOTE Confidence: 0.9621108

00:25:31.744 --> 00:25:33.105
very high risk cancers that

NOTE Confidence: 0.9621108

00:25:33.105 --> 00:25:34.725
have a, you know,

NOTE Confidence: 0.9646209

00:25:35.105 --> 00:25:37.185
potential risk for recurrence and

NOTE Confidence: 0.9646209

00:25:37.185 --> 00:25:38.065
how are we going to

NOTE Confidence: 0.9646209

00:25:38.065 --> 00:25:39.105
kind of use this data

NOTE Confidence: 0.9646209

00:25:39.105 --> 00:25:41.125
and potentially gene expression profiling

NOTE Confidence: 0.98182714

00:25:41.670 --> 00:25:43.130
to to kind of refine

NOTE Confidence: 0.98182714

00:25:43.270 --> 00:25:44.950
our selection of who may

NOTE Confidence: 0.98182714

00:25:44.950 --> 00:25:46.630
warrant adjuvant treatment and who

NOTE Confidence: 0.98182714

00:25:46.630 --> 00:25:47.450
could potentially,

NOTE Confidence: 0.9107423

00:25:48.710 --> 00:25:50.250
forego adjuvant treatment.

NOTE Confidence: 0.97963345

00:25:50.950 --> 00:25:51.450
So,

NOTE Confidence: 0.940883

00:25:52.070 --> 00:25:53.930
as has already been demonstrated

NOTE Confidence: 0.940883

00:25:54.150 --> 00:25:55.845
that the mainstay of treatment

NOTE Confidence: 0.940883

00:25:55.845 --> 00:25:56.825
for skin cancer,

NOTE Confidence: 0.948767

00:25:57.365 --> 00:25:59.065
is for surgery upfront.

NOTE Confidence: 0.9693674

00:26:00.085 --> 00:26:01.365
There are situations in where

NOTE Confidence: 0.9693674

00:26:01.365 --> 00:26:03.205
radiotherapy might be used in

NOTE Confidence: 0.9693674

00:26:03.205 --> 00:26:05.065
the definitive setting. It's usually,

NOTE Confidence: 0.99766016

00:26:05.765 --> 00:26:07.045
reserved for patients who are

NOTE Confidence: 0.99766016

00:26:07.045 --> 00:26:08.345
either deemed unresectable

NOTE Confidence: 0.9848693

00:26:09.125 --> 00:26:10.984
or are refusing surgery itself.

NOTE Confidence: 0.9882151

00:26:12.059 --> 00:26:12.940
When it comes to early

NOTE Confidence: 0.9882151

00:26:12.940 --> 00:26:13.919
stage cutaneous,

NOTE Confidence: 0.8216653

00:26:14.859 --> 00:26:15.359
squamous,

NOTE Confidence: 0.9865479

00:26:15.980 --> 00:26:17.820
radiation has equivalent cure rates

NOTE Confidence: 0.9865479

00:26:17.820 --> 00:26:19.020
to that of surgery, but

NOTE Confidence: 0.9865479

00:26:19.020 --> 00:26:20.799
it is time intensive. Radiation

NOTE Confidence: 0.9865479

00:26:20.940 --> 00:26:22.059
is not a single treatment,

NOTE Confidence: 0.9865479

00:26:22.059 --> 00:26:23.179
much like surgery can be

NOTE Confidence: 0.9865479

00:26:23.179 --> 00:26:24.135
done in a single office

NOTE Confidence: 0.9865479

00:26:24.215 --> 00:26:25.494
visit. This is eight sessions

NOTE Confidence: 0.9865479

00:26:25.494 --> 00:26:26.295
over the course of a

NOTE Confidence: 0.9865479

00:26:26.295 --> 00:26:27.275
month at minimum,

NOTE Confidence: 0.97331995

00:26:27.734 --> 00:26:29.015
but many may require thirty

NOTE Confidence: 0.97331995

00:26:29.015 --> 00:26:30.215
to thirty five sessions over

NOTE Confidence: 0.97331995

00:26:30.215 --> 00:26:31.575
six to seven weeks. And

NOTE Confidence: 0.97331995

00:26:31.575 --> 00:26:32.775
there also are going to

NOTE Confidence: 0.97331995

00:26:32.775 --> 00:26:34.775
be, morbidity and side effects

NOTE Confidence: 0.97331995

00:26:34.775 --> 00:26:36.635
associated with radiation treatment.

NOTE Confidence: 0.961875

00:26:37.710 --> 00:26:39.190
So it's not necessarily going

NOTE Confidence: 0.961875

00:26:39.190 --> 00:26:40.030
to be our go to

NOTE Confidence: 0.961875

00:26:40.030 --> 00:26:41.470
for upfront management and it

NOTE Confidence: 0.961875

00:26:41.470 --> 00:26:43.070
could potentially preclude the use

NOTE Confidence: 0.961875

00:26:43.070 --> 00:26:44.270
of radiation if the patient

NOTE Confidence: 0.961875

00:26:44.270 --> 00:26:45.390
were to ever have a

NOTE Confidence: 0.961875

00:26:45.390 --> 00:26:46.830
second cancer because you really

NOTE Confidence: 0.961875

00:26:46.830 --> 00:26:48.350
can't, shouldn't give radiation to

NOTE Confidence: 0.961875

00:26:48.350 --> 00:26:49.070
the same part of the

NOTE Confidence: 0.961875

00:26:49.070 --> 00:26:49.890
body twice.

NOTE Confidence: 0.99057835

00:26:50.415 --> 00:26:50.915
So

NOTE Confidence: 0.90910864

00:26:51.295 --> 00:26:52.735
therefore radiation is really an

NOTE Confidence: 0.90910864

00:26:52.735 --> 00:26:54.835
adjunct, in the adjuvant setting

NOTE Confidence: 0.90910864

00:26:54.895 --> 00:26:56.255
for high risk or very

NOTE Confidence: 0.90910864

00:26:56.255 --> 00:26:57.475
high risk skin cancers.

NOTE Confidence: 0.9584797

00:26:58.175 --> 00:26:58.975
Now I know that this

NOTE Confidence: 0.9584797

00:26:58.975 --> 00:27:00.895
has already been reviewed to

NOTE Confidence: 0.9584797

00:27:00.895 --> 00:27:02.735
some degree. This is just

NOTE Confidence: 0.9584797

00:27:02.735 --> 00:27:04.095
NCCN guidelines of kind of

NOTE Confidence: 0.9584797

00:27:04.095 --> 00:27:04.835
where radiation

NOTE Confidence: 0.9985327

00:27:05.190 --> 00:27:06.570
therapy may play in

NOTE Confidence: 0.83446133

00:27:06.950 --> 00:27:08.169
in, the

NOTE Confidence: 0.93847954

00:27:09.269 --> 00:27:10.789
care for a patient with

NOTE Confidence: 0.93847954

00:27:10.789 --> 00:27:11.750
a high risk or very

NOTE Confidence: 0.93847954

00:27:11.750 --> 00:27:12.789
high risk skin cancer. And

NOTE Confidence: 0.93847954

00:27:12.789 --> 00:27:13.830
again, just pointing out that

NOTE Confidence: 0.93847954

00:27:13.830 --> 00:27:14.789
this is really at the

NOTE Confidence: 0.93847954

00:27:14.789 --> 00:27:15.609
end of treatment,

NOTE Confidence: 0.9792034

00:27:16.230 --> 00:27:17.990
surgeries performed, you're looking at

NOTE Confidence: 0.9792034

00:27:17.990 --> 00:27:19.450
patients who have positive margins

NOTE Confidence: 0.9792034

00:27:19.510 --> 00:27:21.705
or other pathologic risk factors

NOTE Confidence: 0.9792034

00:27:21.705 --> 00:27:23.145
for those with negative margins

NOTE Confidence: 0.9792034

00:27:23.145 --> 00:27:24.925
that may warrant consideration

NOTE Confidence: 0.9435509

00:27:25.385 --> 00:27:26.685
of radiation therapy.

NOTE Confidence: 0.961782

00:27:28.025 --> 00:27:29.305
We've already seen the risk

NOTE Confidence: 0.961782

00:27:29.305 --> 00:27:29.805
stratification,

NOTE Confidence: 0.91754377

00:27:31.225 --> 00:27:32.105
data that's,

NOTE Confidence: 0.89133

00:27:32.425 --> 00:27:33.869
in the previous presentation, so

NOTE Confidence: 0.89133

00:27:33.869 --> 00:27:34.990
I won't belabor that. But

NOTE Confidence: 0.89133

00:27:34.990 --> 00:27:36.609
again, NCCN has,

NOTE Confidence: 0.9243202

00:27:37.710 --> 00:27:38.990
low risk, high risk, and

NOTE Confidence: 0.9243202

00:27:38.990 --> 00:27:40.050
very high risk,

NOTE Confidence: 0.90974504

00:27:40.430 --> 00:27:42.290
and Brigham and Women similarly

NOTE Confidence: 0.90974504

00:27:42.430 --> 00:27:42.930
has

NOTE Confidence: 0.9164408

00:27:43.310 --> 00:27:45.070
similar pathologic features that would

NOTE Confidence: 0.9164408

00:27:45.070 --> 00:27:46.510
also can be considered as

NOTE Confidence: 0.9164408

00:27:46.510 --> 00:27:47.250
risk factors

NOTE Confidence: 0.9984465

00:27:47.575 --> 00:27:48.855
to maybe help guide those

NOTE Confidence: 0.9984465

00:27:48.855 --> 00:27:49.734
patients who are at higher

NOTE Confidence: 0.9984465

00:27:49.734 --> 00:27:50.795
risk for recurrence.

NOTE Confidence: 0.9629821

00:27:53.095 --> 00:27:54.135
When it comes to adjuvant

NOTE Confidence: 0.9629821

00:27:54.135 --> 00:27:55.895
radiation, again, we're really reserving

NOTE Confidence: 0.9629821

00:27:55.895 --> 00:27:57.015
this usually to our very

NOTE Confidence: 0.9629821

00:27:57.015 --> 00:27:58.615
high risk patients or certain

NOTE Confidence: 0.9629821

00:27:58.615 --> 00:27:59.835
high risk situations

NOTE Confidence: 0.96651983

00:28:00.295 --> 00:28:02.420
like recurrent tumors, patients who

NOTE Confidence: 0.96651983

00:28:02.420 --> 00:28:03.700
are immune suppressed and have

NOTE Confidence: 0.96651983

00:28:03.700 --> 00:28:05.640
higher local recurrence risk,

NOTE Confidence: 0.9883885

00:28:06.180 --> 00:28:07.859
or those with T2B or

NOTE Confidence: 0.9883885

00:28:07.859 --> 00:28:08.680
higher tumors.

NOTE Confidence: 0.9614632

00:28:09.619 --> 00:28:10.119
Interestingly,

NOTE Confidence: 0.9993117

00:28:10.420 --> 00:28:12.680
despite how common cutaneous

NOTE Confidence: 0.9265677

00:28:13.494 --> 00:28:15.355
squamous are, the data,

NOTE Confidence: 0.9770638

00:28:16.135 --> 00:28:17.575
prospective data in terms of

NOTE Confidence: 0.9770638

00:28:17.575 --> 00:28:19.415
the efficacy of adjuvant radiation

NOTE Confidence: 0.9770638

00:28:19.415 --> 00:28:20.875
is really lacking.

NOTE Confidence: 0.927643

00:28:21.415 --> 00:28:22.615
We really much much of

NOTE Confidence: 0.927643

00:28:22.615 --> 00:28:23.415
the data has just been

NOTE Confidence: 0.927643

00:28:23.415 --> 00:28:25.195
derived from retrospective reports,

NOTE Confidence: 0.9247024

00:28:25.575 --> 00:28:26.475
and therefore,

NOTE Confidence: 0.9755883

00:28:27.820 --> 00:28:29.419
really truly teasing out who

NOTE Confidence: 0.9755883

00:28:29.419 --> 00:28:31.019
might truly benefit from treatment

NOTE Confidence: 0.9755883

00:28:31.019 --> 00:28:32.799
or not is is not

NOTE Confidence: 0.9755883

00:28:33.019 --> 00:28:33.919
well defined.

NOTE Confidence: 0.99744356

00:28:34.460 --> 00:28:34.960
Similarly,

NOTE Confidence: 0.9556923

00:28:35.340 --> 00:28:36.559
when it comes to radiation,

NOTE Confidence: 0.9556923

00:28:36.619 --> 00:28:38.480
I'm someone who's offering radiation

NOTE Confidence: 0.9556923

00:28:38.539 --> 00:28:39.500
to a certain part of

NOTE Confidence: 0.9556923

00:28:39.500 --> 00:28:40.885
the body, much like a

NOTE Confidence: 0.9556923

00:28:40.885 --> 00:28:41.925
surgeon is gonna remove the

NOTE Confidence: 0.9556923

00:28:41.925 --> 00:28:42.805
area of the tumor.

NOTE Confidence: 0.9743027

00:28:43.525 --> 00:28:44.345
So radiation,

NOTE Confidence: 0.91634244

00:28:45.925 --> 00:28:46.725
can either be,

NOTE Confidence: 0.97438645

00:28:47.285 --> 00:28:48.725
administered just to the primary

NOTE Confidence: 0.97438645

00:28:48.725 --> 00:28:50.085
site where the where the

NOTE Confidence: 0.97438645

00:28:50.085 --> 00:28:50.585
surgery,

NOTE Confidence: 0.87762195

00:28:51.765 --> 00:28:53.065
removed the tumor itself,

NOTE Confidence: 0.96205825

00:28:53.870 --> 00:28:55.230
especially in a clinically node

NOTE Confidence: 0.96205825

00:28:55.230 --> 00:28:57.550
negative patient, although radiation may

NOTE Confidence: 0.96205825

00:28:57.550 --> 00:28:59.090
also include draining lymphatics.

NOTE Confidence: 0.9341682

00:28:59.710 --> 00:29:01.550
And in these retrospective reports,

NOTE Confidence: 0.9341682

00:29:01.550 --> 00:29:02.590
it's very hard to kinda

NOTE Confidence: 0.9341682

00:29:02.590 --> 00:29:04.030
tease out was this primary

NOTE Confidence: 0.9341682

00:29:04.030 --> 00:29:05.470
site radiation, was it primary

NOTE Confidence: 0.9341682

00:29:05.470 --> 00:29:06.990
plus regional radiation, and so

NOTE Confidence: 0.9341682

00:29:06.990 --> 00:29:08.110
kinda how can we also

NOTE Confidence: 0.9341682

00:29:08.110 --> 00:29:09.605
tease out the efficacy based

NOTE Confidence: 0.9341682

00:29:09.605 --> 00:29:10.965
on our target of the

NOTE Confidence: 0.9341682

00:29:10.965 --> 00:29:13.225
radiation is also less clear.

NOTE Confidence: 0.9372206

00:29:13.685 --> 00:29:14.485
I also want to point

NOTE Confidence: 0.9372206

00:29:14.485 --> 00:29:16.005
out that, you know, we

NOTE Confidence: 0.9372206

00:29:16.005 --> 00:29:17.865
don't want to overdo radiation

NOTE Confidence: 0.9372206

00:29:17.925 --> 00:29:19.045
in every patient who comes

NOTE Confidence: 0.9372206

00:29:19.045 --> 00:29:20.325
to our practice because the

NOTE Confidence: 0.9372206

00:29:20.325 --> 00:29:21.685
more of someone you radiate

NOTE Confidence: 0.9372206

00:29:21.685 --> 00:29:22.645
the more side effects you're

NOTE Confidence: 0.9372206

00:29:22.645 --> 00:29:24.600
gonna then kind of subject

NOTE Confidence: 0.9372206

00:29:24.600 --> 00:29:26.280
that patient to that can

NOTE Confidence: 0.9372206

00:29:26.280 --> 00:29:27.480
affect life on quality of

NOTE Confidence: 0.9372206

00:29:27.480 --> 00:29:27.880
life,

NOTE Confidence: 0.9808006

00:29:28.360 --> 00:29:29.400
especially if you're talking about

NOTE Confidence: 0.9808006

00:29:29.400 --> 00:29:30.200
things in the head and

NOTE Confidence: 0.9808006

00:29:30.200 --> 00:29:31.400
neck region where you're talking

NOTE Confidence: 0.9808006

00:29:31.400 --> 00:29:33.400
about salivary gland exposure, dry

NOTE Confidence: 0.9808006

00:29:33.400 --> 00:29:34.700
mouth, lymphedema,

NOTE Confidence: 0.9600466

00:29:35.000 --> 00:29:36.975
scar tissue, and also potentially

NOTE Confidence: 0.9600466

00:29:36.975 --> 00:29:38.735
again eliminating radiation as an

NOTE Confidence: 0.9600466

00:29:38.735 --> 00:29:39.934
option should there be another

NOTE Confidence: 0.9600466

00:29:39.934 --> 00:29:41.555
cancer in this person's lifetime.

NOTE Confidence: 0.93489045

00:29:43.934 --> 00:29:45.155
Kind of to the point

NOTE Confidence: 0.93489045

00:29:45.375 --> 00:29:45.875
of

NOTE Confidence: 0.87799484

00:29:46.255 --> 00:29:48.595
the limited prospective data regarding

NOTE Confidence: 0.87799484

00:29:48.735 --> 00:29:50.175
the efficacy of adjuvant radiation

NOTE Confidence: 0.87799484

00:29:50.175 --> 00:29:51.295
we really don't have much

NOTE Confidence: 0.87799484

00:29:51.295 --> 00:29:52.035
but there

NOTE Confidence: 0.96490777

00:29:52.600 --> 00:29:53.960
just in the last few

NOTE Confidence: 0.96490777

00:29:53.960 --> 00:29:55.980
months another very large retrospective

NOTE Confidence: 0.96490777

00:29:56.279 --> 00:29:58.759
cohort was described with patients

NOTE Confidence: 0.96490777

00:29:58.759 --> 00:30:00.220
with very high risk disease,

NOTE Confidence: 0.9515292

00:30:01.240 --> 00:30:03.980
including multiple institutions where they

NOTE Confidence: 0.9515292

00:30:04.039 --> 00:30:05.559
looked into their databases finding

NOTE Confidence: 0.9515292

00:30:05.559 --> 00:30:07.184
twelve sixty seven patients who

NOTE Confidence: 0.9515292

00:30:07.184 --> 00:30:08.705
met high risk criteria but

NOTE Confidence: 0.9515292

00:30:08.705 --> 00:30:10.404
of note only twelve percent

NOTE Confidence: 0.9515292

00:30:10.544 --> 00:30:12.144
or so are receiving adjuvant

NOTE Confidence: 0.9515292

00:30:12.144 --> 00:30:13.205
radiation treatment.

NOTE Confidence: 0.9621716

00:30:14.065 --> 00:30:16.304
But in this retrospective cohort

NOTE Confidence: 0.9621716

00:30:16.304 --> 00:30:17.184
what we do find is

NOTE Confidence: 0.9621716

00:30:17.184 --> 00:30:18.865
adjuvant radiation does reduce the

NOTE Confidence: 0.9621716

00:30:18.865 --> 00:30:20.304
risk of both local, local

NOTE Confidence: 0.9621716

00:30:20.304 --> 00:30:21.700
regional as well as nodal

NOTE Confidence: 0.9621716

00:30:21.700 --> 00:30:23.460
recurrence by fifty percent. And

NOTE Confidence: 0.9621716

00:30:23.460 --> 00:30:24.500
here are just the Kaplan

NOTE Confidence: 0.9621716

00:30:24.500 --> 00:30:26.279
Meier curves demonstrating that.

NOTE Confidence: 0.9637089

00:30:26.980 --> 00:30:28.580
Importantly, and I think where

NOTE Confidence: 0.9637089

00:30:28.580 --> 00:30:29.940
we, you know, where gene

NOTE Confidence: 0.9637089

00:30:29.940 --> 00:30:31.460
expression profiling might come in,

NOTE Confidence: 0.9637089

00:30:31.700 --> 00:30:33.139
to help sub stratify is

NOTE Confidence: 0.9637089

00:30:33.139 --> 00:30:34.904
is we're not seeing overall

NOTE Confidence: 0.9637089

00:30:34.904 --> 00:30:36.585
survival benefit. We're definitely seeing

NOTE Confidence: 0.9637089

00:30:36.585 --> 00:30:38.505
local control benefit and there's

NOTE Confidence: 0.9637089

00:30:38.505 --> 00:30:39.465
value to that but we're

NOTE Confidence: 0.9637089

00:30:39.465 --> 00:30:41.065
not necessarily seeing a survival

NOTE Confidence: 0.9637089

00:30:41.065 --> 00:30:41.945
benefit. So if we can

NOTE Confidence: 0.9637089

00:30:41.945 --> 00:30:43.385
identify those patients who could

NOTE Confidence: 0.9637089

00:30:43.385 --> 00:30:45.304
potentially have a survival benefit

NOTE Confidence: 0.9637089

00:30:45.304 --> 00:30:46.265
it might also help us

NOTE Confidence: 0.9637089

00:30:46.265 --> 00:30:47.580
prevent that patient who may

NOTE Confidence: 0.9637089

00:30:47.820 --> 00:30:49.100
ultimately succumb as the second

NOTE Confidence: 0.9637089

00:30:49.100 --> 00:30:50.480
case in the previous presentation.

NOTE Confidence: 0.899041

00:30:51.820 --> 00:30:53.200
So within this this

NOTE Confidence: 0.92836255

00:30:53.580 --> 00:30:55.500
particular retrospective series they did

NOTE Confidence: 0.92836255

00:30:55.500 --> 00:30:56.539
want to look at patients

NOTE Confidence: 0.92836255

00:30:56.539 --> 00:30:57.740
who may have higher risk

NOTE Confidence: 0.92836255

00:30:57.740 --> 00:30:59.019
disease and they kind of

NOTE Confidence: 0.92836255

00:30:59.019 --> 00:31:00.779
sub stratified this by patients

NOTE Confidence: 0.92836255

00:31:00.779 --> 00:31:02.059
who are t2b but with

NOTE Confidence: 0.92836255

00:31:02.059 --> 00:31:03.120
three of the criteria,

NOTE Confidence: 0.9708246

00:31:04.195 --> 00:31:04.935
the T3s

NOTE Confidence: 0.9393389

00:31:05.235 --> 00:31:06.435
as well as those with

NOTE Confidence: 0.9393389

00:31:06.435 --> 00:31:07.955
LVI and they found within

NOTE Confidence: 0.9393389

00:31:07.955 --> 00:31:09.715
that twelve hundred patients, two

NOTE Confidence: 0.9393389

00:31:09.715 --> 00:31:11.395
forty six, that met this

NOTE Confidence: 0.9393389

00:31:11.395 --> 00:31:12.695
higher risk subtype,

NOTE Confidence: 0.99363256

00:31:13.155 --> 00:31:14.775
thirty percent of that population

NOTE Confidence: 0.99363256

00:31:14.835 --> 00:31:16.375
did receive adjuvant treatment.

NOTE Confidence: 0.9584459

00:31:16.830 --> 00:31:19.409
And we're, we're still seeing

NOTE Confidence: 0.9584459

00:31:19.630 --> 00:31:21.150
similarly a fifty percent reduction

NOTE Confidence: 0.9584459

00:31:21.150 --> 00:31:22.590
in local recurrence but certainly

NOTE Confidence: 0.9584459

00:31:22.590 --> 00:31:24.190
that absolute benefit is better

NOTE Confidence: 0.9584459

00:31:24.190 --> 00:31:25.630
because you've now identified a

NOTE Confidence: 0.9584459

00:31:25.630 --> 00:31:27.309
potentially higher risk subgroup so

NOTE Confidence: 0.9584459

00:31:27.309 --> 00:31:28.510
those patients are more likely

NOTE Confidence: 0.9584459

00:31:28.510 --> 00:31:30.015
to benefit. Still not seeing

NOTE Confidence: 0.9584459

00:31:30.015 --> 00:31:31.235
a disease specific,

NOTE Confidence: 0.96293026

00:31:31.775 --> 00:31:33.155
survival benefit, however.

NOTE Confidence: 0.9973664

00:31:35.215 --> 00:31:36.735
This is where, you know,

NOTE Confidence: 0.9973664

00:31:36.735 --> 00:31:38.735
gene expression profiling is is

NOTE Confidence: 0.9973664

00:31:38.895 --> 00:31:40.095
there's a lot of optimism

NOTE Confidence: 0.9973664

00:31:40.095 --> 00:31:41.375
that this could potentially help

NOTE Confidence: 0.9973664

00:31:41.375 --> 00:31:42.975
further identify subgroups that may

NOTE Confidence: 0.9973664

00:31:42.975 --> 00:31:44.115
benefit from radiotherapy.

NOTE Confidence: 0.823434

00:31:46.040 --> 00:31:46.620
So, you

NOTE Confidence: 0.95034724

00:31:47.240 --> 00:31:48.920
know, in incorporating this in

NOTE Confidence: 0.95034724

00:31:48.920 --> 00:31:50.200
future randomized trials I think

NOTE Confidence: 0.95034724

00:31:50.200 --> 00:31:51.480
will also really be important

NOTE Confidence: 0.95034724

00:31:51.480 --> 00:31:52.700
of trying to help delineate,

NOTE Confidence: 0.94990313

00:31:53.320 --> 00:31:54.300
without bias,

NOTE Confidence: 0.90388095

00:31:54.840 --> 00:31:56.600
how radiation therapy may may

NOTE Confidence: 0.90388095

00:31:56.600 --> 00:31:57.260
be beneficial,

NOTE Confidence: 0.9963746

00:31:57.720 --> 00:31:58.940
in this group of patients.

NOTE Confidence: 0.97348386

00:32:00.735 --> 00:32:01.715
I wanted to

NOTE Confidence: 0.9993655

00:32:02.015 --> 00:32:02.515
present

NOTE Confidence: 0.9864706

00:32:03.855 --> 00:32:04.815
the same group that has

NOTE Confidence: 0.9864706

00:32:04.815 --> 00:32:06.595
this forty gene expression profile

NOTE Confidence: 0.9864706

00:32:06.735 --> 00:32:07.235
panel

NOTE Confidence: 0.9166836

00:32:07.535 --> 00:32:09.075
also looked at their database

NOTE Confidence: 0.9166836

00:32:09.135 --> 00:32:10.815
of the patients comparing those

NOTE Confidence: 0.9166836

00:32:10.815 --> 00:32:12.495
who had radiation and who

NOTE Confidence: 0.9166836

00:32:12.495 --> 00:32:13.235
did not.

NOTE Confidence: 0.9338859

00:32:13.919 --> 00:32:15.200
And they are seeing a

NOTE Confidence: 0.9338859

00:32:15.200 --> 00:32:15.700
benefit

NOTE Confidence: 0.9691408

00:32:16.399 --> 00:32:17.279
or being able to use

NOTE Confidence: 0.9691408

00:32:17.279 --> 00:32:18.559
their class system to help

NOTE Confidence: 0.9691408

00:32:18.559 --> 00:32:20.320
identify subgroups of patients that

NOTE Confidence: 0.9691408

00:32:20.320 --> 00:32:21.759
may actually truly benefit from

NOTE Confidence: 0.9691408

00:32:21.759 --> 00:32:22.259
radiotherapy

NOTE Confidence: 0.98856664

00:32:22.559 --> 00:32:23.360
and those who may have

NOTE Confidence: 0.98856664

00:32:23.360 --> 00:32:24.340
lower risk disease

NOTE Confidence: 0.98107326

00:32:24.720 --> 00:32:27.039
despite classically being considered high

NOTE Confidence: 0.98107326

00:32:27.039 --> 00:32:28.419
risk or very high risk

NOTE Confidence: 0.9286401

00:32:28.835 --> 00:32:30.215
who could potentially

NOTE Confidence: 0.97265244

00:32:30.595 --> 00:32:32.275
omit radiotherapy as part of

NOTE Confidence: 0.97265244

00:32:32.275 --> 00:32:32.935
their care.

NOTE Confidence: 0.9775853

00:32:33.475 --> 00:32:33.975
So

NOTE Confidence: 0.79555035

00:32:35.075 --> 00:32:36.755
specifically they again this is

NOTE Confidence: 0.79555035

00:32:36.755 --> 00:32:37.895
a gene expression profiling

NOTE Confidence: 0.9742888

00:32:38.835 --> 00:32:40.515
looking at in total about

NOTE Confidence: 0.9742888

00:32:40.515 --> 00:32:41.955
four hundred and some patients

NOTE Confidence: 0.9742888

00:32:41.955 --> 00:32:42.775
in this particular

NOTE Confidence: 0.98852587

00:32:43.710 --> 00:32:44.830
cohort of patients that they

NOTE Confidence: 0.98852587

00:32:44.830 --> 00:32:46.990
evaluated who had classically high

NOTE Confidence: 0.98852587

00:32:46.990 --> 00:32:48.590
risk disease or very high

NOTE Confidence: 0.98852587

00:32:48.590 --> 00:32:49.409
risk disease

NOTE Confidence: 0.7636641

00:32:49.870 --> 00:32:50.690
but subclassifying

NOTE Confidence: 0.9372527

00:32:51.070 --> 00:32:52.350
them into the class I,

NOTE Confidence: 0.9372527

00:32:52.350 --> 00:32:53.390
the class IIA or the

NOTE Confidence: 0.9372527

00:32:53.390 --> 00:32:54.510
class IIB based on the

NOTE Confidence: 0.9372527

00:32:54.510 --> 00:32:55.809
gene expression profiling.

NOTE Confidence: 0.9054027

00:32:56.565 --> 00:32:58.085
Again small numbers only about

NOTE Confidence: 0.9054027

00:32:58.085 --> 00:32:59.524
thirteen twelve twelve to thirteen

NOTE Confidence: 0.9054027

00:32:59.524 --> 00:33:00.804
percent of patients actually receiving

NOTE Confidence: 0.9054027

00:33:00.804 --> 00:33:02.085
adjuvant treatment in this group

NOTE Confidence: 0.9054027

00:33:02.085 --> 00:33:03.365
but kind of spread across

NOTE Confidence: 0.9054027

00:33:03.365 --> 00:33:04.885
class 1a, class 2a and

NOTE Confidence: 0.9054027

00:33:04.885 --> 00:33:05.705
class 2b.

NOTE Confidence: 0.96719426

00:33:06.245 --> 00:33:07.284
And when they again look

NOTE Confidence: 0.96719426

00:33:07.284 --> 00:33:08.580
at the Kaplan Meier curves

NOTE Confidence: 0.96719426

00:33:08.580 --> 00:33:09.779
where we're seeing the largest

NOTE Confidence: 0.96719426

00:33:09.779 --> 00:33:11.059
benefit in the left side

NOTE Confidence: 0.96719426

00:33:11.059 --> 00:33:12.520
of the screen here are

NOTE Confidence: 0.96719426

00:33:12.580 --> 00:33:14.340
the class 2b patients. Their

NOTE Confidence: 0.96719426

00:33:14.340 --> 00:33:15.720
risk of metastasis

NOTE Confidence: 0.7443925

00:33:16.820 --> 00:33:17.220
with,

NOTE Confidence: 0.9991143

00:33:18.020 --> 00:33:19.000
without radiotherapy

NOTE Confidence: 0.9606346

00:33:19.700 --> 00:33:21.220
are indicated by that dotted

NOTE Confidence: 0.9606346

00:33:21.220 --> 00:33:22.200
line in red.

NOTE Confidence: 0.9930747

00:33:22.575 --> 00:33:24.095
Whereas those that did receive

NOTE Confidence: 0.9930747

00:33:24.095 --> 00:33:24.595
radiotherapy

NOTE Confidence: 0.9941157

00:33:24.895 --> 00:33:26.515
actually had a dramatic benefit

NOTE Confidence: 0.9564004

00:33:26.895 --> 00:33:28.174
reduction in risk of recurrence.

NOTE Confidence: 0.9564004

00:33:28.174 --> 00:33:29.534
Now these are low numbers

NOTE Confidence: 0.9564004

00:33:29.534 --> 00:33:30.735
but it does you know

NOTE Confidence: 0.9564004

00:33:30.735 --> 00:33:32.015
suggest that we could identify

NOTE Confidence: 0.9564004

00:33:32.015 --> 00:33:33.135
a group that's more likely

NOTE Confidence: 0.9564004

00:33:33.135 --> 00:33:34.515
to benefit from radiotherapy.

NOTE Confidence: 0.922159

00:33:36.010 --> 00:33:37.450
The right sided panel really

NOTE Confidence: 0.922159

00:33:37.450 --> 00:33:39.050
just kind of shows this

NOTE Confidence: 0.922159

00:33:39.050 --> 00:33:40.250
this benefit in in a

NOTE Confidence: 0.922159

00:33:40.250 --> 00:33:42.010
different graphical way where class

NOTE Confidence: 0.922159

00:33:42.010 --> 00:33:42.910
one a patients,

NOTE Confidence: 0.99918336

00:33:43.450 --> 00:33:45.470
despite meeting high risk criteria

NOTE Confidence: 0.96707785

00:33:45.770 --> 00:33:47.470
based on gene expression profiling

NOTE Confidence: 0.96310055

00:33:47.975 --> 00:33:48.935
from the small group of

NOTE Confidence: 0.96310055

00:33:48.935 --> 00:33:50.235
patients may not necessarily

NOTE Confidence: 0.9767514

00:33:50.615 --> 00:33:52.295
benefit from adjuvant treatment because

NOTE Confidence: 0.9767514

00:33:52.295 --> 00:33:53.735
their risk seems to already

NOTE Confidence: 0.9767514

00:33:53.735 --> 00:33:54.855
be so low of recurrence

NOTE Confidence: 0.9767514

00:33:54.855 --> 00:33:55.355
already.

NOTE Confidence: 0.9315859

00:33:55.735 --> 00:33:57.015
Whereas those with class two

NOTE Confidence: 0.9315859

00:33:57.015 --> 00:33:58.055
a are those where we

NOTE Confidence: 0.9315859

00:33:58.055 --> 00:33:59.355
might consider radiotherapy.

NOTE Confidence: 0.96861076

00:33:59.735 --> 00:34:00.535
There does seem to be

NOTE Confidence: 0.96861076

00:34:00.535 --> 00:34:02.710
some potential benefit there, but

NOTE Confidence: 0.96861076

00:34:02.710 --> 00:34:03.670
not quite as much of

NOTE Confidence: 0.96861076

00:34:03.670 --> 00:34:04.630
a benefit as what we're

NOTE Confidence: 0.96861076

00:34:04.630 --> 00:34:05.670
seeing in in that small

NOTE Confidence: 0.96861076

00:34:05.670 --> 00:34:06.870
group of two class two

NOTE Confidence: 0.96861076

00:34:06.870 --> 00:34:07.530
b patients.

NOTE Confidence: 0.974698

00:34:09.270 --> 00:34:10.150
So some of the take

NOTE Confidence: 0.974698

00:34:10.150 --> 00:34:11.430
home points I take from

NOTE Confidence: 0.974698

00:34:11.430 --> 00:34:13.190
from the the forty, you

NOTE Confidence: 0.974698

00:34:13.190 --> 00:34:14.870
know, gene expression panel that's

NOTE Confidence: 0.974698

00:34:14.870 --> 00:34:16.230
available out there is is

NOTE Confidence: 0.974698

00:34:16.230 --> 00:34:17.424
that I think we need

NOTE Confidence: 0.974698

00:34:17.424 --> 00:34:19.285
prospective trials to better understand,

NOTE Confidence: 0.9742615

00:34:19.984 --> 00:34:21.344
you know, how we can

NOTE Confidence: 0.9742615

00:34:21.344 --> 00:34:23.744
identify patients who benefit from

NOTE Confidence: 0.9742615

00:34:23.744 --> 00:34:25.424
this tool to help us

NOTE Confidence: 0.9742615

00:34:25.424 --> 00:34:26.864
better stratify our patients in

NOTE Confidence: 0.9742615

00:34:26.864 --> 00:34:28.565
terms of risk reductive adjuvant

NOTE Confidence: 0.9742615

00:34:28.625 --> 00:34:29.125
strategies.

NOTE Confidence: 0.9810977

00:34:30.300 --> 00:34:32.060
In this retrospective cohort of

NOTE Confidence: 0.9810977

00:34:32.060 --> 00:34:32.560
patients,

NOTE Confidence: 0.9507538

00:34:33.100 --> 00:34:34.700
against small numbers, but it

NOTE Confidence: 0.9507538

00:34:34.700 --> 00:34:36.540
would seem that they have

NOTE Confidence: 0.9507538

00:34:36.540 --> 00:34:37.040
identified

NOTE Confidence: 0.94275194

00:34:37.660 --> 00:34:39.440
a class one gene expression

NOTE Confidence: 0.94275194

00:34:39.500 --> 00:34:40.400
profile that

NOTE Confidence: 0.99926907

00:34:41.100 --> 00:34:41.600
may

NOTE Confidence: 0.9990584

00:34:42.060 --> 00:34:42.560
help

NOTE Confidence: 0.9852717

00:34:43.005 --> 00:34:44.224
determine patients that

NOTE Confidence: 0.954978

00:34:44.924 --> 00:34:46.625
radiation could be safely omitted,

NOTE Confidence: 0.954978

00:34:46.684 --> 00:34:47.885
it could help reduce cost

NOTE Confidence: 0.954978

00:34:47.885 --> 00:34:49.164
of the healthcare system, but

NOTE Confidence: 0.954978

00:34:49.164 --> 00:34:50.924
also importantly prevent putting someone

NOTE Confidence: 0.954978

00:34:50.924 --> 00:34:52.045
through side effects that could

NOTE Confidence: 0.954978

00:34:52.045 --> 00:34:53.244
affect quality of life moving

NOTE Confidence: 0.954978

00:34:53.244 --> 00:34:54.285
forward because of the side

NOTE Confidence: 0.954978

00:34:54.285 --> 00:34:56.385
effects radiation can cause.

NOTE Confidence: 0.96982974

00:34:57.530 --> 00:34:58.570
I think what's gonna be

NOTE Confidence: 0.96982974

00:34:58.570 --> 00:34:59.609
an important question to be

NOTE Confidence: 0.96982974

00:34:59.609 --> 00:35:01.050
answered is how do I

NOTE Confidence: 0.96982974

00:35:01.130 --> 00:35:02.090
how do we know what

NOTE Confidence: 0.96982974

00:35:02.090 --> 00:35:03.290
the benefit of radiation is

NOTE Confidence: 0.96982974

00:35:03.290 --> 00:35:04.410
in terms of what part

NOTE Confidence: 0.96982974

00:35:04.410 --> 00:35:05.630
of the body we're treating?

NOTE Confidence: 0.96982974

00:35:05.849 --> 00:35:07.530
So I mentioned earlier, there's

NOTE Confidence: 0.96982974

00:35:07.530 --> 00:35:08.730
no clear guidance in terms

NOTE Confidence: 0.96982974

00:35:08.730 --> 00:35:09.530
of do you treat the

NOTE Confidence: 0.96982974

00:35:09.530 --> 00:35:10.969
tumors tumor bed only or

NOTE Confidence: 0.96982974

00:35:10.969 --> 00:35:11.770
do you treat the tumor

NOTE Confidence: 0.96982974

00:35:11.770 --> 00:35:12.910
bed plus the nodes?

NOTE Confidence: 0.9974878

00:35:13.505 --> 00:35:14.705
I do know that there

NOTE Confidence: 0.9974878

00:35:14.705 --> 00:35:15.985
is interest in a,

NOTE Confidence: 0.7995587

00:35:16.545 --> 00:35:17.045
in,

NOTE Confidence: 0.98098385

00:35:17.985 --> 00:35:19.425
randomized trial to be designed

NOTE Confidence: 0.98098385

00:35:19.425 --> 00:35:21.105
where they would stratify patients

NOTE Confidence: 0.98098385

00:35:21.105 --> 00:35:22.225
based on class two a

NOTE Confidence: 0.98098385

00:35:22.225 --> 00:35:23.364
or class two b,

NOTE Confidence: 0.99880624

00:35:23.665 --> 00:35:24.165
randomizing

NOTE Confidence: 0.96095395

00:35:24.465 --> 00:35:26.250
them to radiation to the

NOTE Confidence: 0.96095395

00:35:26.250 --> 00:35:28.250
tumor bed only versus tumor

NOTE Confidence: 0.96095395

00:35:28.250 --> 00:35:30.090
bed plus nodal radiation, and

NOTE Confidence: 0.96095395

00:35:30.090 --> 00:35:31.050
c, are we seeing a

NOTE Confidence: 0.96095395

00:35:31.050 --> 00:35:32.489
benefit? Because it's not clear

NOTE Confidence: 0.96095395

00:35:32.489 --> 00:35:33.370
if you just radiate the

NOTE Confidence: 0.96095395

00:35:33.370 --> 00:35:34.810
primary site. Maybe we're preventing

NOTE Confidence: 0.96095395

00:35:34.810 --> 00:35:36.170
cancer cells from spreading to

NOTE Confidence: 0.96095395

00:35:36.170 --> 00:35:37.130
the nodes, and and maybe

NOTE Confidence: 0.96095395

00:35:37.130 --> 00:35:38.090
all the benefit is just

NOTE Confidence: 0.96095395

00:35:38.090 --> 00:35:39.465
treating the tumor bed. So

NOTE Confidence: 0.96095395

00:35:39.545 --> 00:35:40.745
so this trial is hoping

NOTE Confidence: 0.96095395

00:35:40.745 --> 00:35:41.325
to to

NOTE Confidence: 0.99208456

00:35:41.705 --> 00:35:42.925
kind of identify

NOTE Confidence: 0.97674805

00:35:43.225 --> 00:35:44.505
where where the benefit comes

NOTE Confidence: 0.97674805

00:35:44.505 --> 00:35:46.445
because if radiation is important

NOTE Confidence: 0.97674805

00:35:46.585 --> 00:35:48.125
as a risk reductive strategy,

NOTE Confidence: 0.97674805

00:35:48.344 --> 00:35:49.705
but we can identify a

NOTE Confidence: 0.97674805

00:35:49.705 --> 00:35:51.705
more localized radiation field that

NOTE Confidence: 0.97674805

00:35:51.705 --> 00:35:52.825
has less side effects for

NOTE Confidence: 0.97674805

00:35:52.825 --> 00:35:53.785
a patient with the same

NOTE Confidence: 0.97674805

00:35:53.785 --> 00:35:54.285
benefit,

NOTE Confidence: 0.96310616

00:35:54.869 --> 00:35:55.989
I I think that's important

NOTE Confidence: 0.96310616

00:35:55.989 --> 00:35:57.289
for us to to understand.

NOTE Confidence: 0.957676

00:35:57.750 --> 00:35:59.349
And also this prospective trial

NOTE Confidence: 0.957676

00:35:59.349 --> 00:36:01.989
would theoretically also help confirm

NOTE Confidence: 0.957676

00:36:01.989 --> 00:36:03.430
in a prospective manner class

NOTE Confidence: 0.957676

00:36:03.430 --> 00:36:04.950
one patients could safely have

NOTE Confidence: 0.957676

00:36:04.950 --> 00:36:06.089
radiation omitted.

NOTE Confidence: 0.97857815

00:36:06.630 --> 00:36:07.989
And then long long, you

NOTE Confidence: 0.97857815

00:36:07.989 --> 00:36:09.369
know, big picture is

NOTE Confidence: 0.97629184

00:36:10.485 --> 00:36:11.765
a small number, only about

NOTE Confidence: 0.97629184

00:36:11.765 --> 00:36:12.885
twelve percent of patients based

NOTE Confidence: 0.97629184

00:36:12.885 --> 00:36:13.525
on a lot of these,

NOTE Confidence: 0.97629184

00:36:13.525 --> 00:36:14.885
you know, retrospective studies are

NOTE Confidence: 0.97629184

00:36:14.885 --> 00:36:16.185
actually receiving radiotherapy

NOTE Confidence: 0.9094516

00:36:16.485 --> 00:36:17.845
despite meeting a high risk,

NOTE Confidence: 0.9094516

00:36:17.845 --> 00:36:18.985
very high risk categories.

NOTE Confidence: 0.9734986

00:36:20.885 --> 00:36:22.585
Can this gene expression profiling

NOTE Confidence: 0.9734986

00:36:22.885 --> 00:36:24.660
help, again, identify those patients

NOTE Confidence: 0.9734986

00:36:24.660 --> 00:36:25.780
who do have higher risk,

NOTE Confidence: 0.9734986

00:36:25.780 --> 00:36:26.739
who would have a greater

NOTE Confidence: 0.9734986

00:36:26.739 --> 00:36:27.700
benefit so that we could

NOTE Confidence: 0.9734986

00:36:27.700 --> 00:36:29.480
help prevent morbidity of recurrence?

NOTE Confidence: 0.9939175

00:36:30.180 --> 00:36:31.300
Are those the patients that

NOTE Confidence: 0.9939175

00:36:31.300 --> 00:36:32.500
it's worth putting through side

NOTE Confidence: 0.9939175

00:36:32.500 --> 00:36:33.619
effects and making sure we're

NOTE Confidence: 0.9939175

00:36:33.619 --> 00:36:34.900
kind of funneling into the

NOTE Confidence: 0.9939175

00:36:34.900 --> 00:36:35.880
radiation oncology,

NOTE Confidence: 0.94050586

00:36:36.420 --> 00:36:37.800
you know, adjuvant therapy?

NOTE Confidence: 0.98675656

00:36:38.645 --> 00:36:40.165
And having that shared decision

NOTE Confidence: 0.98675656

00:36:40.165 --> 00:36:41.844
making, discussion with the patient

NOTE Confidence: 0.98675656

00:36:41.844 --> 00:36:43.125
is also really helpful. Having

NOTE Confidence: 0.98675656

00:36:43.125 --> 00:36:44.825
this gene profile class

NOTE Confidence: 0.98443985

00:36:45.125 --> 00:36:46.805
stratification might help a patient

NOTE Confidence: 0.98443985

00:36:46.805 --> 00:36:47.945
make an informed decision.

NOTE Confidence: 0.9941731

00:36:48.565 --> 00:36:49.685
Since we're not seeing a

NOTE Confidence: 0.9941731

00:36:49.685 --> 00:36:51.685
survival benefit necessarily based on

NOTE Confidence: 0.9941731

00:36:51.685 --> 00:36:52.665
the small numbers,

NOTE Confidence: 0.9847354

00:36:53.100 --> 00:36:54.540
It's really coming down to

NOTE Confidence: 0.9847354

00:36:54.540 --> 00:36:55.660
how much do they value

NOTE Confidence: 0.9847354

00:36:55.660 --> 00:36:57.440
preventing a local recurrence potentially.

NOTE Confidence: 0.99627066

00:36:58.380 --> 00:36:59.980
And how we view these

NOTE Confidence: 0.99627066

00:36:59.980 --> 00:37:01.580
gene expression panels and how

NOTE Confidence: 0.99627066

00:37:01.580 --> 00:37:03.739
we incorporate our medical decision

NOTE Confidence: 0.99627066

00:37:03.739 --> 00:37:05.420
making about adjuvant radiation is

NOTE Confidence: 0.99627066

00:37:05.420 --> 00:37:06.780
probably also going to be

NOTE Confidence: 0.99627066

00:37:06.780 --> 00:37:07.920
ultimately influenced

NOTE Confidence: 0.9843912

00:37:08.625 --> 00:37:10.545
by systemic therapy options becoming

NOTE Confidence: 0.9843912

00:37:10.545 --> 00:37:11.045
available.

NOTE Confidence: 0.95564103

00:37:11.344 --> 00:37:12.465
Doctor. Tramm will talk about

NOTE Confidence: 0.95564103

00:37:12.465 --> 00:37:13.185
this kind of at the

NOTE Confidence: 0.95564103

00:37:13.185 --> 00:37:15.025
end summarizing this, but, you

NOTE Confidence: 0.95564103

00:37:15.025 --> 00:37:16.545
know, other systemic therapies that

NOTE Confidence: 0.95564103

00:37:16.545 --> 00:37:18.145
are available, other risk reductive

NOTE Confidence: 0.95564103

00:37:18.145 --> 00:37:19.344
strategies that may have a

NOTE Confidence: 0.95564103

00:37:19.344 --> 00:37:20.645
different side effect profile

NOTE Confidence: 0.955302

00:37:20.980 --> 00:37:22.500
may also frame how we

NOTE Confidence: 0.955302

00:37:22.500 --> 00:37:24.340
offer adjuvant treatment even in

NOTE Confidence: 0.955302

00:37:24.340 --> 00:37:25.300
the gene expression,

NOTE Confidence: 0.9943783

00:37:25.620 --> 00:37:26.680
profiling era.

NOTE Confidence: 0.9749109

00:37:31.060 --> 00:37:32.580
That's wonderful. I don't see

NOTE Confidence: 0.9749109

00:37:32.580 --> 00:37:34.260
any questions in the chat

NOTE Confidence: 0.9749109

00:37:34.260 --> 00:37:35.219
or the Q and A,

NOTE Confidence: 0.9749109

00:37:35.219 --> 00:37:36.440
but just want to remind

NOTE Confidence: 0.9970696

00:37:36.825 --> 00:37:37.964
everyone to please

NOTE Confidence: 0.99774337

00:37:38.265 --> 00:37:39.244
ask us questions.

NOTE Confidence: 0.8592836

00:37:40.265 --> 00:37:41.625
You know, doctor Roche, I

NOTE Confidence: 0.8592836

00:37:41.625 --> 00:37:43.145
was curious, and also doctor

NOTE Confidence: 0.8592836

00:37:43.145 --> 00:37:43.645
Susie,

NOTE Confidence: 0.92697746

00:37:44.025 --> 00:37:45.505
if you had had received

NOTE Confidence: 0.92697746

00:37:45.705 --> 00:37:46.825
and I asked doctor Roche

NOTE Confidence: 0.92697746

00:37:46.825 --> 00:37:48.265
as she's our our PI

NOTE Confidence: 0.92697746

00:37:48.265 --> 00:37:49.864
locally of the NRG Neo

NOTE Confidence: 0.92697746

00:37:49.864 --> 00:37:50.364
adjuvant

NOTE Confidence: 0.99869746

00:37:50.790 --> 00:37:53.450
cutaneous squamous cell carcinoma trial.

NOTE Confidence: 0.99892473

00:37:54.070 --> 00:37:55.110
Would you be more or

NOTE Confidence: 0.99892473

00:37:55.110 --> 00:37:57.030
less likely to enroll a

NOTE Confidence: 0.99892473

00:37:57.030 --> 00:37:58.469
patient that maybe had a

NOTE Confidence: 0.99892473

00:37:58.469 --> 00:37:58.969
smaller

NOTE Confidence: 0.9665803

00:37:59.670 --> 00:38:00.870
tumor that you may not

NOTE Confidence: 0.9665803

00:38:00.870 --> 00:38:02.570
have been as suspicious about

NOTE Confidence: 0.99209493

00:38:02.950 --> 00:38:04.250
if they had a category

NOTE Confidence: 0.99209493

00:38:04.390 --> 00:38:05.670
two a or b on

NOTE Confidence: 0.99209493

00:38:05.670 --> 00:38:06.489
your trial?

NOTE Confidence: 0.94356924

00:38:07.535 --> 00:38:08.575
Yep. You're referring to the

NOTE Confidence: 0.94356924

00:38:08.575 --> 00:38:11.295
neoadjuvant simlopimab trial? That's yep.

NOTE Confidence: 0.94356924

00:38:11.295 --> 00:38:11.795
Yeah.

NOTE Confidence: 0.96999216

00:38:12.095 --> 00:38:14.255
So a smaller tumor, but

NOTE Confidence: 0.96999216

00:38:14.255 --> 00:38:15.555
a higher higher,

NOTE Confidence: 0.97003204

00:38:16.415 --> 00:38:18.575
biological class on the gene

NOTE Confidence: 0.97003204

00:38:18.575 --> 00:38:19.075
panel.

NOTE Confidence: 0.9627186

00:38:19.989 --> 00:38:20.950
I would I you know,

NOTE Confidence: 0.9627186

00:38:20.950 --> 00:38:22.550
it's interesting because we as

NOTE Confidence: 0.9627186

00:38:22.550 --> 00:38:23.050
we're

NOTE Confidence: 0.98541623

00:38:23.590 --> 00:38:25.030
accruing for this trial and

NOTE Confidence: 0.98541623

00:38:25.030 --> 00:38:26.870
seeing how patients do, you

NOTE Confidence: 0.98541623

00:38:26.870 --> 00:38:28.390
know, it overall has a

NOTE Confidence: 0.98541623

00:38:28.390 --> 00:38:30.010
has a very substantial

NOTE Confidence: 0.9736475

00:38:31.635 --> 00:38:33.495
success rate in previous studies,

NOTE Confidence: 0.99660605

00:38:34.195 --> 00:38:35.235
but we are seeing some

NOTE Confidence: 0.99660605

00:38:35.235 --> 00:38:36.295
patients progressing.

NOTE Confidence: 0.9847063

00:38:36.915 --> 00:38:38.295
And so I do wonder,

NOTE Confidence: 0.9847063

00:38:38.355 --> 00:38:39.555
and I've you know, as

NOTE Confidence: 0.9847063

00:38:39.555 --> 00:38:40.755
as we've been talking about

NOTE Confidence: 0.9847063

00:38:40.755 --> 00:38:42.375
this, I've I was thinking,

NOTE Confidence: 0.9847063

00:38:42.515 --> 00:38:43.795
is is this something that

NOTE Confidence: 0.9847063

00:38:43.795 --> 00:38:45.395
could be added to an

NOTE Confidence: 0.9847063

00:38:45.395 --> 00:38:46.855
existing clinical trial,

NOTE Confidence: 0.9799761

00:38:47.500 --> 00:38:49.100
as an additional piece of

NOTE Confidence: 0.9799761

00:38:49.100 --> 00:38:50.300
information to have about these

NOTE Confidence: 0.9799761

00:38:50.300 --> 00:38:50.800
tumors,

NOTE Confidence: 0.9650616

00:38:51.660 --> 00:38:53.420
we have patients that respond

NOTE Confidence: 0.9650616

00:38:53.420 --> 00:38:54.480
very well to suniplumab,

NOTE Confidence: 0.98431104

00:38:54.780 --> 00:38:56.140
and then we're seeing patients

NOTE Confidence: 0.98431104

00:38:56.140 --> 00:38:57.260
that don't respond and that

NOTE Confidence: 0.98431104

00:38:57.260 --> 00:38:57.920
they progress.

NOTE Confidence: 0.98627913

00:38:58.940 --> 00:39:00.540
So this could be, you

NOTE Confidence: 0.98627913

00:39:00.540 --> 00:39:02.480
know, provide some missing information.

NOTE Confidence: 0.98921025

00:39:03.075 --> 00:39:04.594
But having that information to

NOTE Confidence: 0.98921025

00:39:04.594 --> 00:39:05.335
your point,

NOTE Confidence: 0.985822

00:39:05.635 --> 00:39:07.315
you know, might might raise

NOTE Confidence: 0.985822

00:39:07.315 --> 00:39:08.835
some questions about maybe they

NOTE Confidence: 0.985822

00:39:08.835 --> 00:39:09.635
should just go ahead and

NOTE Confidence: 0.985822

00:39:09.635 --> 00:39:10.375
have surgery,

NOTE Confidence: 0.9588481

00:39:11.474 --> 00:39:12.375
rather than,

NOTE Confidence: 0.9779666

00:39:13.075 --> 00:39:14.035
rather than enroll in a

NOTE Confidence: 0.9779666

00:39:14.035 --> 00:39:14.935
clinical trial.

NOTE Confidence: 0.99473035

00:39:15.520 --> 00:39:16.960
I would also say that,

NOTE Confidence: 0.9597996

00:39:19.120 --> 00:39:20.320
in response to that question

NOTE Confidence: 0.9597996

00:39:20.320 --> 00:39:22.000
about enrollment in the clinical

NOTE Confidence: 0.9597996

00:39:22.000 --> 00:39:23.280
trial is that one of

NOTE Confidence: 0.9597996

00:39:23.280 --> 00:39:24.320
the issues is sometimes we

NOTE Confidence: 0.9597996

00:39:24.320 --> 00:39:25.600
don't have the full staging

NOTE Confidence: 0.9597996

00:39:25.600 --> 00:39:27.200
picture until after they have

NOTE Confidence: 0.9597996

00:39:27.200 --> 00:39:28.560
the MOSE procedure. Right? If

NOTE Confidence: 0.9597996

00:39:28.560 --> 00:39:30.580
the perineural invasion is not

NOTE Confidence: 0.9970377

00:39:30.945 --> 00:39:32.565
captured in the original biopsy,

NOTE Confidence: 0.9970377

00:39:32.625 --> 00:39:33.844
we're not realizing

NOTE Confidence: 0.9963707

00:39:34.145 --> 00:39:34.645
until,

NOTE Confidence: 0.73888713

00:39:35.344 --> 00:39:36.405
their full stage

NOTE Confidence: 0.9460439

00:39:36.705 --> 00:39:38.305
until after they've had surgery.

NOTE Confidence: 0.9460439

00:39:38.305 --> 00:39:40.065
So having that GEP class

NOTE Confidence: 0.9460439

00:39:40.065 --> 00:39:41.045
prior to surgery,

NOTE Confidence: 0.9712155

00:39:41.905 --> 00:39:43.125
can help restratify,

NOTE Confidence: 0.9990504

00:39:44.145 --> 00:39:45.265
when you may not have

NOTE Confidence: 0.9990504

00:39:45.265 --> 00:39:46.450
all of the high risk

NOTE Confidence: 0.9990504

00:39:46.450 --> 00:39:47.430
features identified

NOTE Confidence: 0.93907565

00:39:48.050 --> 00:39:49.190
prior pre op.

NOTE Confidence: 0.99711823

00:39:52.130 --> 00:39:52.630
Okay.

NOTE Confidence: 0.9966122

00:39:53.810 --> 00:39:55.750
So we're gonna shift gears

NOTE Confidence: 0.86842954

00:39:56.210 --> 00:39:56.450
and,

NOTE Confidence: 0.9935365

00:39:57.170 --> 00:39:58.530
go into the magical world

NOTE Confidence: 0.9935365

00:39:58.530 --> 00:39:59.190
of melanoma.

NOTE Confidence: 0.9545364

00:40:02.214 --> 00:40:03.175
But, you know, some of

NOTE Confidence: 0.9545364

00:40:03.175 --> 00:40:04.855
my introduction is really gonna

NOTE Confidence: 0.9545364

00:40:04.855 --> 00:40:05.355
amplify

NOTE Confidence: 0.9987147

00:40:05.734 --> 00:40:06.795
some incredibly

NOTE Confidence: 0.9997286

00:40:07.335 --> 00:40:07.835
important

NOTE Confidence: 0.9099519

00:40:08.135 --> 00:40:09.675
points that have already been

NOTE Confidence: 0.9099519

00:40:09.815 --> 00:40:11.675
made by doctor Young.

NOTE Confidence: 0.96491313

00:40:12.535 --> 00:40:13.915
I'll share my screen.

NOTE Confidence: 0.4472357

00:40:20.980 --> 00:40:21.480
Screen,

NOTE Confidence: 0.9449503

00:40:22.820 --> 00:40:23.960
it's visible, everyone?

NOTE Confidence: 0.9988291

00:40:24.660 --> 00:40:25.160
Okay.

NOTE Confidence: 0.9987349

00:40:26.180 --> 00:40:26.680
So

NOTE Confidence: 0.9978935

00:40:28.100 --> 00:40:28.600
the

NOTE Confidence: 0.99880254

00:40:29.465 --> 00:40:31.325
current landscape for melanoma

NOTE Confidence: 0.99605787

00:40:31.705 --> 00:40:33.385
about how we determine high

NOTE Confidence: 0.99605787

00:40:33.385 --> 00:40:35.325
risk disease is very different

NOTE Confidence: 0.99605787

00:40:35.545 --> 00:40:36.045
than

NOTE Confidence: 0.9707799

00:40:36.505 --> 00:40:38.125
where we are with cutaneous

NOTE Confidence: 0.9707799

00:40:38.265 --> 00:40:40.585
squamous cell. So again, mostly

NOTE Confidence: 0.9707799

00:40:40.585 --> 00:40:41.965
based on clinical pathologic

NOTE Confidence: 0.71437615

00:40:42.265 --> 00:40:42.765
features.

NOTE Confidence: 0.9433182

00:40:43.350 --> 00:40:45.290
And, really importantly, for melanoma,

NOTE Confidence: 0.97907597

00:40:45.590 --> 00:40:47.830
we really routinely use sentinel

NOTE Confidence: 0.97907597

00:40:47.830 --> 00:40:49.830
node biopsy based on the

NOTE Confidence: 0.97907597

00:40:49.830 --> 00:40:51.050
MSLT one

NOTE Confidence: 0.95873547

00:40:52.390 --> 00:40:54.070
trial. And the clinical path

NOTE Confidence: 0.95873547

00:40:54.070 --> 00:40:55.430
features, many of which, you

NOTE Confidence: 0.95873547

00:40:55.430 --> 00:40:56.550
know, similar to what doctor

NOTE Confidence: 0.95873547

00:40:56.550 --> 00:40:58.410
Suzy had begun the conversation

NOTE Confidence: 0.95873547

00:40:58.550 --> 00:40:59.775
with, are are some very,

NOTE Confidence: 0.95873547

00:40:59.775 --> 00:41:00.994
very well validated,

NOTE Confidence: 0.9728546

00:41:03.135 --> 00:41:03.635
nomograms.

NOTE Confidence: 0.99935

00:41:04.335 --> 00:41:05.454
And some of the recent

NOTE Confidence: 0.99935

00:41:05.454 --> 00:41:05.954
changes

NOTE Confidence: 0.9984423

00:41:06.255 --> 00:41:07.474
to the

NOTE Confidence: 0.995121

00:41:07.934 --> 00:41:09.155
NCCN guidelines

NOTE Confidence: 0.9657033

00:41:10.015 --> 00:41:12.675
are incorporating actually using nomogram

NOTE Confidence: 0.9657033

00:41:12.734 --> 00:41:14.849
driven risk factors instead of

NOTE Confidence: 0.9657033

00:41:14.849 --> 00:41:15.589
the classic

NOTE Confidence: 0.9958793

00:41:16.130 --> 00:41:17.029
clinical pathologic

NOTE Confidence: 0.99547654

00:41:17.410 --> 00:41:18.770
features that had driven those

NOTE Confidence: 0.99547654

00:41:18.770 --> 00:41:19.750
decision making

NOTE Confidence: 0.8758049

00:41:20.450 --> 00:41:21.750
processes. But universally,

NOTE Confidence: 0.9994023

00:41:22.289 --> 00:41:22.789
as

NOTE Confidence: 0.9592367

00:41:23.089 --> 00:41:24.130
a as a group, we've

NOTE Confidence: 0.9592367

00:41:24.130 --> 00:41:24.950
agreed that

NOTE Confidence: 0.9785118

00:41:25.250 --> 00:41:26.950
a sentinel lymph node biopsy

NOTE Confidence: 0.9785118

00:41:27.010 --> 00:41:28.609
risk between five to ten

NOTE Confidence: 0.9785118

00:41:28.609 --> 00:41:29.085
percent

NOTE Confidence: 0.9030574

00:41:29.565 --> 00:41:30.945
requires a discussion,

NOTE Confidence: 0.9846792

00:41:31.484 --> 00:41:32.785
and ten or above

NOTE Confidence: 0.9961709

00:41:33.484 --> 00:41:35.425
usually will be typically recommended

NOTE Confidence: 0.9961709

00:41:35.484 --> 00:41:37.185
for a medically fit patient

NOTE Confidence: 0.9946211

00:41:37.645 --> 00:41:38.925
in which the results of

NOTE Confidence: 0.9946211

00:41:38.925 --> 00:41:40.525
the sentinel node are actually

NOTE Confidence: 0.9946211

00:41:40.525 --> 00:41:41.665
going to be impactful.

NOTE Confidence: 0.796526

00:41:42.150 --> 00:41:42.650
And

NOTE Confidence: 0.98701054

00:41:43.029 --> 00:41:44.549
remember, the sentinel node is

NOTE Confidence: 0.98701054

00:41:44.549 --> 00:41:45.989
what we use for risk

NOTE Confidence: 0.98701054

00:41:45.989 --> 00:41:46.489
prognostication

NOTE Confidence: 0.9143166

00:41:46.869 --> 00:41:47.369
to

NOTE Confidence: 0.99992573

00:41:48.309 --> 00:41:48.809
better

NOTE Confidence: 0.9993119

00:41:49.109 --> 00:41:49.609
delineate

NOTE Confidence: 0.9771616

00:41:49.989 --> 00:41:51.430
where we are. Are we

NOTE Confidence: 0.9771616

00:41:51.430 --> 00:41:52.710
stage one? Are we stage

NOTE Confidence: 0.9771616

00:41:52.710 --> 00:41:54.089
three? Where are we in

NOTE Confidence: 0.9771616

00:41:54.230 --> 00:41:55.910
between? And it really has

NOTE Confidence: 0.9771616

00:41:55.910 --> 00:41:56.890
a great discriminatory

NOTE Confidence: 0.8856238

00:41:57.270 --> 00:41:57.770
value.

NOTE Confidence: 0.9485425

00:41:58.125 --> 00:41:59.805
However, we're always faced with

NOTE Confidence: 0.9485425

00:41:59.805 --> 00:42:01.505
the challenges. You know,

NOTE Confidence: 0.97506535

00:42:01.885 --> 00:42:04.045
our overtreated patient. Right? There's

NOTE Confidence: 0.97506535

00:42:04.045 --> 00:42:05.565
gonna be some patients in

NOTE Confidence: 0.97506535

00:42:05.565 --> 00:42:07.005
melanoma that are gonna be

NOTE Confidence: 0.97506535

00:42:07.005 --> 00:42:08.065
cured by surgery

NOTE Confidence: 0.9992761

00:42:08.605 --> 00:42:10.285
alone. They don't gain anything

NOTE Confidence: 0.9992761

00:42:10.285 --> 00:42:11.940
by watching them closer. They

NOTE Confidence: 0.9992761

00:42:11.940 --> 00:42:12.839
don't gain anything

NOTE Confidence: 0.9713555

00:42:13.380 --> 00:42:15.079
from getting adjuvant therapy,

NOTE Confidence: 0.94957525

00:42:15.540 --> 00:42:17.160
but they bear real financial

NOTE Confidence: 0.94957525

00:42:17.300 --> 00:42:18.980
and emotional cost as well

NOTE Confidence: 0.94957525

00:42:18.980 --> 00:42:19.719
as toxicity.

NOTE Confidence: 0.9893172

00:42:21.140 --> 00:42:22.180
Then we have the other

NOTE Confidence: 0.9893172

00:42:22.180 --> 00:42:23.540
patients that we're missing, the

NOTE Confidence: 0.9893172

00:42:23.540 --> 00:42:25.700
undertreated patients. And, you know,

NOTE Confidence: 0.9893172

00:42:25.700 --> 00:42:26.739
we worry a lot about

NOTE Confidence: 0.9893172

00:42:26.739 --> 00:42:28.385
these in our most common

NOTE Confidence: 0.9893172

00:42:28.445 --> 00:42:30.364
presentation for melanoma, which is

NOTE Confidence: 0.9893172

00:42:30.364 --> 00:42:31.905
our earlier stage patients.

NOTE Confidence: 0.94502974

00:42:32.205 --> 00:42:33.165
We know there's a small

NOTE Confidence: 0.94502974

00:42:33.165 --> 00:42:34.844
percentage of these patients that

NOTE Confidence: 0.94502974

00:42:34.844 --> 00:42:35.585
are recur

NOTE Confidence: 0.7128343

00:42:36.125 --> 00:42:36.625
and

NOTE Confidence: 0.9997461

00:42:36.925 --> 00:42:37.825
they go untreated

NOTE Confidence: 0.9216212

00:42:38.125 --> 00:42:39.745
and that group gets missed.

NOTE Confidence: 0.98612165

00:42:40.380 --> 00:42:41.339
And when we think about

NOTE Confidence: 0.98612165

00:42:41.339 --> 00:42:42.719
it, it becomes an amplified

NOTE Confidence: 0.98612165

00:42:42.779 --> 00:42:43.819
problem. So we have a

NOTE Confidence: 0.98612165

00:42:43.819 --> 00:42:45.420
very small percentage, but that

NOTE Confidence: 0.98612165

00:42:45.420 --> 00:42:45.920
percentage

NOTE Confidence: 0.9877628

00:42:46.619 --> 00:42:47.119
absolutely

NOTE Confidence: 0.9712384

00:42:47.900 --> 00:42:49.339
represents a large group of

NOTE Confidence: 0.9712384

00:42:49.339 --> 00:42:50.859
patients because if, you know,

NOTE Confidence: 0.9712384

00:42:50.859 --> 00:42:52.059
over eighty percent of our

NOTE Confidence: 0.9712384

00:42:52.059 --> 00:42:53.099
patients are going to be

NOTE Confidence: 0.9712384

00:42:53.099 --> 00:42:54.719
early, even a small percentage

NOTE Confidence: 0.9712384

00:42:54.859 --> 00:42:56.665
of that becomes a bigger

NOTE Confidence: 0.9712384

00:42:56.665 --> 00:42:57.165
problem.

NOTE Confidence: 0.9766441

00:42:57.704 --> 00:42:58.984
And, again, our overall goal

NOTE Confidence: 0.9766441

00:42:58.984 --> 00:43:00.025
is we only want to

NOTE Confidence: 0.9766441

00:43:00.025 --> 00:43:01.224
treat patients that are going

NOTE Confidence: 0.9766441

00:43:01.224 --> 00:43:02.585
to relapse. We want to

NOTE Confidence: 0.9766441

00:43:02.585 --> 00:43:03.944
spare anyone that would be

NOTE Confidence: 0.9766441

00:43:03.944 --> 00:43:05.385
cured with surgery. And in

NOTE Confidence: 0.9766441

00:43:05.385 --> 00:43:06.344
order to do this, we

NOTE Confidence: 0.9766441

00:43:06.344 --> 00:43:07.464
have to try to be

NOTE Confidence: 0.9766441

00:43:07.464 --> 00:43:07.964
better

NOTE Confidence: 0.9952738

00:43:08.265 --> 00:43:09.964
at accurate risk stratification.

NOTE Confidence: 0.89113235

00:43:11.719 --> 00:43:12.859
So again, our AJCC

NOTE Confidence: 0.9779466

00:43:13.160 --> 00:43:15.079
staging, it's it's good, but

NOTE Confidence: 0.9779466

00:43:15.079 --> 00:43:17.000
it's not sufficient. We're striving

NOTE Confidence: 0.9779466

00:43:17.000 --> 00:43:17.960
to keep doing that. That's

NOTE Confidence: 0.9779466

00:43:17.960 --> 00:43:19.559
why it's always iterative, why

NOTE Confidence: 0.9779466

00:43:19.559 --> 00:43:20.460
it gets improved.

NOTE Confidence: 0.93415344

00:43:20.839 --> 00:43:22.200
So it does provide some

NOTE Confidence: 0.93415344

00:43:22.200 --> 00:43:23.660
valuable baseline prognostication,

NOTE Confidence: 0.9673

00:43:24.695 --> 00:43:25.335
but there's a lot of

NOTE Confidence: 0.9673

00:43:25.335 --> 00:43:25.835
heterogeneity,

NOTE Confidence: 0.96833384

00:43:26.295 --> 00:43:27.494
there's a lot of overlap

NOTE Confidence: 0.96833384

00:43:27.494 --> 00:43:29.094
within these categories that we're

NOTE Confidence: 0.96833384

00:43:29.094 --> 00:43:30.695
working to parse out. And

NOTE Confidence: 0.96833384

00:43:30.695 --> 00:43:32.455
again, that's the question about

NOTE Confidence: 0.96833384

00:43:32.455 --> 00:43:34.135
not only nomograms, but does

NOTE Confidence: 0.96833384

00:43:34.135 --> 00:43:35.275
the GEP testing

NOTE Confidence: 0.99955124

00:43:36.055 --> 00:43:37.175
help us to get a

NOTE Confidence: 0.99955124

00:43:37.175 --> 00:43:37.915
more individualized

NOTE Confidence: 0.9769976

00:43:38.295 --> 00:43:39.594
risk for these patients?

NOTE Confidence: 0.93624485

00:43:41.170 --> 00:43:42.710
Again, that stage 1b2a

NOTE Confidence: 0.9589772

00:43:43.570 --> 00:43:44.770
patient group is really where

NOTE Confidence: 0.9589772

00:43:44.770 --> 00:43:46.050
I think that this is

NOTE Confidence: 0.9589772

00:43:46.050 --> 00:43:48.050
a real unmet need where

NOTE Confidence: 0.9589772

00:43:48.050 --> 00:43:49.330
we may be under treating

NOTE Confidence: 0.9589772

00:43:49.330 --> 00:43:50.310
but also overtreating

NOTE Confidence: 0.9555136

00:43:50.610 --> 00:43:51.750
part of that population,

NOTE Confidence: 0.9989309

00:43:52.770 --> 00:43:53.270
so

NOTE Confidence: 0.9997818

00:43:53.964 --> 00:43:54.844
we really need to be

NOTE Confidence: 0.9997818

00:43:54.844 --> 00:43:56.545
able to distinguish these groups

NOTE Confidence: 0.95899975

00:43:58.204 --> 00:44:00.125
so gene expression profile arrays

NOTE Confidence: 0.95899975

00:44:00.125 --> 00:44:01.645
have been around for almost

NOTE Confidence: 0.95899975

00:44:01.645 --> 00:44:03.744
fifteen years now in melanoma,

NOTE Confidence: 0.95899975

00:44:03.885 --> 00:44:05.405
again much earlier in their

NOTE Confidence: 0.95899975

00:44:05.405 --> 00:44:07.025
inception and use for cutaneous

NOTE Confidence: 0.95899975

00:44:07.165 --> 00:44:08.920
squamous cell And there's three

NOTE Confidence: 0.95899975

00:44:08.920 --> 00:44:10.200
main ones that are commercially

NOTE Confidence: 0.95899975

00:44:10.200 --> 00:44:10.700
available,

NOTE Confidence: 0.92641586

00:44:11.480 --> 00:44:13.160
two available in the States.

NOTE Confidence: 0.92641586

00:44:13.160 --> 00:44:14.760
One is only available in

NOTE Confidence: 0.92641586

00:44:14.760 --> 00:44:16.460
Germany, so the Castle Bioscience

NOTE Confidence: 0.92641586

00:44:16.600 --> 00:44:17.260
is probably

NOTE Confidence: 0.9650706

00:44:17.560 --> 00:44:18.760
the oldest one that had

NOTE Confidence: 0.9650706

00:44:18.760 --> 00:44:20.520
been used. The more recent

NOTE Confidence: 0.9650706

00:44:20.520 --> 00:44:21.739
one is the,

NOTE Confidence: 0.909567

00:44:22.445 --> 00:44:23.185
the CPGEP,

NOTE Confidence: 0.98042995

00:44:23.805 --> 00:44:25.185
commonly known as the Merlin

NOTE Confidence: 0.89494693

00:44:25.565 --> 00:44:26.065
assay,

NOTE Confidence: 0.9438585

00:44:27.165 --> 00:44:28.765
which will speak in great

NOTE Confidence: 0.9438585

00:44:28.765 --> 00:44:30.364
detail, both myself and Doctor.

NOTE Confidence: 0.9438585

00:44:30.364 --> 00:44:30.864
Christiansen.

NOTE Confidence: 0.97474796

00:44:31.405 --> 00:44:33.105
And then an eleven gene

NOTE Confidence: 0.9631763

00:44:33.405 --> 00:44:35.165
GEP, the Melligenics, and that's

NOTE Confidence: 0.9631763

00:44:35.165 --> 00:44:36.465
used over in Germany.

NOTE Confidence: 0.9763998

00:44:37.349 --> 00:44:38.950
Each of them actually use

NOTE Confidence: 0.9763998

00:44:38.950 --> 00:44:41.130
completely different genes. So within

NOTE Confidence: 0.9763998

00:44:41.190 --> 00:44:42.390
all of these,

NOTE Confidence: 0.9933293

00:44:42.789 --> 00:44:44.549
prognostic and reference genes, they

NOTE Confidence: 0.9933293

00:44:44.549 --> 00:44:45.930
actually do not overlap.

NOTE Confidence: 0.94780844

00:44:47.509 --> 00:44:48.569
Some use clinical

NOTE Confidence: 0.9409482

00:44:49.075 --> 00:44:50.515
pathologic variables, so that's in

NOTE Confidence: 0.9409482

00:44:50.515 --> 00:44:52.515
the DECISION DX as well

NOTE Confidence: 0.9409482

00:44:52.515 --> 00:44:53.955
as the Merlin assay, but

NOTE Confidence: 0.9409482

00:44:53.955 --> 00:44:55.094
not in the melaninics.

NOTE Confidence: 0.9630313

00:44:56.355 --> 00:44:58.755
The output in the DECISION

NOTE Confidence: 0.9630313

00:44:58.755 --> 00:45:00.455
DX, the thirty one GEP,

NOTE Confidence: 0.9630313

00:45:00.675 --> 00:45:02.535
when it includes clinical pathologic,

NOTE Confidence: 0.9630313

00:45:02.594 --> 00:45:03.849
that makes it the I

NOTE Confidence: 0.9630313

00:45:03.849 --> 00:45:04.910
thirty one GEP.

NOTE Confidence: 0.91668946

00:45:05.210 --> 00:45:07.130
That's broken into four different

NOTE Confidence: 0.91668946

00:45:07.130 --> 00:45:08.650
classes versus the other two

NOTE Confidence: 0.91668946

00:45:08.650 --> 00:45:10.489
are really higher low risk

NOTE Confidence: 0.91668946

00:45:10.489 --> 00:45:11.550
binary categories.

NOTE Confidence: 0.9991773

00:45:12.890 --> 00:45:13.390
The

NOTE Confidence: 0.9954693

00:45:13.690 --> 00:45:14.830
thirty one GEP,

NOTE Confidence: 0.96450984

00:45:15.295 --> 00:45:17.135
that was initially developed actually

NOTE Confidence: 0.96450984

00:45:17.135 --> 00:45:18.515
for overall prognosis,

NOTE Confidence: 0.99576336

00:45:18.895 --> 00:45:20.094
but then is now more

NOTE Confidence: 0.99576336

00:45:20.094 --> 00:45:21.395
developed towards giving

NOTE Confidence: 0.9766879

00:45:21.855 --> 00:45:22.975
some guidance for who we

NOTE Confidence: 0.9766879

00:45:22.975 --> 00:45:24.594
should be doing sentinel nodes.

NOTE Confidence: 0.9766879

00:45:24.655 --> 00:45:26.255
Merlin assay was really more

NOTE Confidence: 0.9766879

00:45:26.255 --> 00:45:27.855
developed with sentinel nodes, although

NOTE Confidence: 0.9766879

00:45:27.855 --> 00:45:29.955
there is perhaps some prognostic

NOTE Confidence: 0.9650008

00:45:30.590 --> 00:45:31.630
cation that can be done

NOTE Confidence: 0.9650008

00:45:31.630 --> 00:45:32.910
versus the g e the

NOTE Confidence: 0.9650008

00:45:32.910 --> 00:45:34.430
eleven g e p is

NOTE Confidence: 0.9650008

00:45:34.430 --> 00:45:36.510
really focused on stage two

NOTE Confidence: 0.9650008

00:45:36.510 --> 00:45:37.010
disease

NOTE Confidence: 0.9974237

00:45:37.469 --> 00:45:38.370
and prognostic

NOTE Confidence: 0.9876342

00:45:38.830 --> 00:45:39.330
variables.

NOTE Confidence: 0.9966446

00:45:40.270 --> 00:45:41.410
These can be variably

NOTE Confidence: 0.9533157

00:45:41.870 --> 00:45:42.910
reimbursed. If we look at

NOTE Confidence: 0.9533157

00:45:42.910 --> 00:45:44.190
the cost of a sentinel

NOTE Confidence: 0.9533157

00:45:44.190 --> 00:45:45.315
node, that can range from

NOTE Confidence: 0.9533157

00:45:45.315 --> 00:45:46.994
nine to eleven thousand dollars

NOTE Confidence: 0.9533157

00:45:46.994 --> 00:45:47.815
in the states,

NOTE Confidence: 0.9930105

00:45:48.594 --> 00:45:50.214
and some of these GEP

NOTE Confidence: 0.9930105

00:45:50.355 --> 00:45:51.954
assays can cost, if they're

NOTE Confidence: 0.9930105

00:45:51.954 --> 00:45:53.974
not covered by insurance, anywhere

NOTE Confidence: 0.9930105

00:45:54.035 --> 00:45:54.535
from,

NOTE Confidence: 0.92165685

00:45:55.075 --> 00:45:56.835
three to seven thousand dollars

NOTE Confidence: 0.92165685

00:45:56.835 --> 00:45:58.695
depending upon insurance status.

NOTE Confidence: 0.9611006

00:45:59.360 --> 00:46:00.640
So and right now, the

NOTE Confidence: 0.9611006

00:46:00.640 --> 00:46:02.480
thirty one GEP has not

NOTE Confidence: 0.9611006

00:46:02.480 --> 00:46:03.219
been recommended

NOTE Confidence: 0.99823594

00:46:03.680 --> 00:46:05.219
by any of the major

NOTE Confidence: 0.99823594

00:46:05.280 --> 00:46:05.780
societies.

NOTE Confidence: 0.95564806

00:46:06.480 --> 00:46:08.180
Just this year, the NCCN

NOTE Confidence: 0.95564806

00:46:08.400 --> 00:46:09.920
on the basis of the,

NOTE Confidence: 0.95564806

00:46:10.239 --> 00:46:11.860
Merlin o o one randomized

NOTE Confidence: 0.95564806

00:46:11.920 --> 00:46:12.820
clinical trial,

NOTE Confidence: 0.9486222

00:46:13.364 --> 00:46:14.665
has included this.

NOTE Confidence: 0.96961516

00:46:15.364 --> 00:46:16.805
And there is actually and

NOTE Confidence: 0.96961516

00:46:16.805 --> 00:46:17.844
doctor Tran will talk a

NOTE Confidence: 0.96961516

00:46:17.844 --> 00:46:18.725
little bit more about the

NOTE Confidence: 0.96961516

00:46:18.725 --> 00:46:20.585
nivo mela phase three trial,

NOTE Confidence: 0.96961516

00:46:20.645 --> 00:46:22.085
which is actually doing a

NOTE Confidence: 0.9627005

00:46:23.445 --> 00:46:24.885
identifying the high risk group

NOTE Confidence: 0.9627005

00:46:24.885 --> 00:46:25.945
and actually randomizing

NOTE Confidence: 0.99053174

00:46:26.550 --> 00:46:28.390
those patients to receive either

NOTE Confidence: 0.99053174

00:46:28.390 --> 00:46:29.450
adjuvant nivolumab

NOTE Confidence: 0.9988209

00:46:29.910 --> 00:46:30.650
or placebo

NOTE Confidence: 0.9930682

00:46:31.190 --> 00:46:32.550
for our high risk stage

NOTE Confidence: 0.9930682

00:46:32.550 --> 00:46:33.290
two patients.

NOTE Confidence: 0.9960973

00:46:34.710 --> 00:46:36.070
So looking a little bit

NOTE Confidence: 0.9960973

00:46:36.070 --> 00:46:37.430
into what is the best

NOTE Confidence: 0.9960973

00:46:37.430 --> 00:46:38.730
data that's available

NOTE Confidence: 0.942372

00:46:39.030 --> 00:46:40.310
to review, so for the

NOTE Confidence: 0.942372

00:46:40.310 --> 00:46:41.290
thirty one GEP,

NOTE Confidence: 0.87090546

00:46:41.715 --> 00:46:43.415
there was a prospective decide

NOTE Confidence: 0.87090546

00:46:43.475 --> 00:46:43.975
study,

NOTE Confidence: 0.957361

00:46:44.835 --> 00:46:45.335
again,

NOTE Confidence: 0.99370116

00:46:45.795 --> 00:46:47.075
for what it was looking

NOTE Confidence: 0.99370116

00:46:47.075 --> 00:46:48.435
for. So the negative predictive

NOTE Confidence: 0.99370116

00:46:48.435 --> 00:46:49.715
value means how much can

NOTE Confidence: 0.99370116

00:46:49.715 --> 00:46:51.415
you trust when someone says

NOTE Confidence: 0.9857334

00:46:52.835 --> 00:46:54.215
that this is not gonna

NOTE Confidence: 0.94951624

00:46:54.760 --> 00:46:56.280
be a positive sentinel note,

NOTE Confidence: 0.94951624

00:46:56.280 --> 00:46:57.880
so very, very good negative

NOTE Confidence: 0.94951624

00:46:57.880 --> 00:46:58.380
predictive

NOTE Confidence: 0.9891372

00:46:58.760 --> 00:47:00.780
value in these low risk

NOTE Confidence: 0.9891372

00:47:00.920 --> 00:47:02.360
patients, which you want. There's

NOTE Confidence: 0.9891372

00:47:02.360 --> 00:47:03.720
a low prevalence. We don't

NOTE Confidence: 0.9891372

00:47:03.720 --> 00:47:04.520
wanna have a lot of

NOTE Confidence: 0.9891372

00:47:04.520 --> 00:47:06.520
people that have disease that

NOTE Confidence: 0.9891372

00:47:06.520 --> 00:47:07.580
we didn't detect.

NOTE Confidence: 0.9952264

00:47:08.520 --> 00:47:09.020
Now

NOTE Confidence: 0.9185629

00:47:09.714 --> 00:47:11.255
the problem though is that

NOTE Confidence: 0.9643221

00:47:11.635 --> 00:47:12.915
it not very good at

NOTE Confidence: 0.9643221

00:47:12.915 --> 00:47:15.094
identifying who are the outliers.

NOTE Confidence: 0.98080194

00:47:15.474 --> 00:47:17.315
Right? If everybody in your

NOTE Confidence: 0.98080194

00:47:17.315 --> 00:47:19.075
test, they can identify and

NOTE Confidence: 0.98080194

00:47:19.075 --> 00:47:20.355
I we already said that

NOTE Confidence: 0.98080194

00:47:20.355 --> 00:47:21.474
there are t one a

NOTE Confidence: 0.98080194

00:47:21.474 --> 00:47:22.835
patients that are going to

NOTE Confidence: 0.98080194

00:47:22.835 --> 00:47:23.335
relapse.

NOTE Confidence: 0.97209525

00:47:23.850 --> 00:47:25.310
If your test can't discriminate

NOTE Confidence: 0.97209525

00:47:25.450 --> 00:47:27.450
between that, you know, there

NOTE Confidence: 0.97209525

00:47:27.450 --> 00:47:29.130
there becomes some issue. But,

NOTE Confidence: 0.97209525

00:47:29.130 --> 00:47:30.970
again, if it's negative, that

NOTE Confidence: 0.97209525

00:47:30.970 --> 00:47:33.050
negative predictive value seems to

NOTE Confidence: 0.97209525

00:47:33.050 --> 00:47:34.750
be very good with this.

NOTE Confidence: 0.8644496

00:47:35.844 --> 00:47:37.685
The MERLIN one is the

NOTE Confidence: 0.8644496

00:47:37.685 --> 00:47:38.585
largest prospective

NOTE Confidence: 0.95520216

00:47:38.885 --> 00:47:40.805
GEP trial to date, you

NOTE Confidence: 0.95520216

00:47:40.805 --> 00:47:42.344
know, seventeen hundred

NOTE Confidence: 0.9605166

00:47:42.645 --> 00:47:43.145
patients,

NOTE Confidence: 0.9288656

00:47:44.085 --> 00:47:46.405
looking from, again, T1a through

NOTE Confidence: 0.9288656

00:47:46.405 --> 00:47:46.905
T3.

NOTE Confidence: 0.9372866

00:47:47.605 --> 00:47:49.364
Again, at patients who we're

NOTE Confidence: 0.9372866

00:47:49.364 --> 00:47:50.880
the most worried about and

NOTE Confidence: 0.9372866

00:47:50.880 --> 00:47:52.160
I think that there's very

NOTE Confidence: 0.9372866

00:47:52.160 --> 00:47:53.359
little debate whether or not

NOTE Confidence: 0.9372866

00:47:53.359 --> 00:47:54.480
they should get a sentinel

NOTE Confidence: 0.9372866

00:47:54.480 --> 00:47:55.219
node biopsy,

NOTE Confidence: 0.9372299

00:47:55.839 --> 00:47:56.339
again,

NOTE Confidence: 0.9371035

00:47:57.680 --> 00:47:59.200
it's really not going to

NOTE Confidence: 0.9371035

00:47:59.200 --> 00:48:00.420
be that discriminatory.

NOTE Confidence: 0.98454326

00:48:01.119 --> 00:48:02.480
However, in the group of

NOTE Confidence: 0.98454326

00:48:02.480 --> 00:48:04.215
patients here, these high risk

NOTE Confidence: 0.98454326

00:48:04.215 --> 00:48:05.575
t one a's, t one

NOTE Confidence: 0.98454326

00:48:05.575 --> 00:48:07.495
b's, t two a's, these

NOTE Confidence: 0.98454326

00:48:07.495 --> 00:48:08.555
are our class,

NOTE Confidence: 0.9742887

00:48:09.175 --> 00:48:11.114
clinical stage one b patients.

NOTE Confidence: 0.9742887

00:48:11.175 --> 00:48:11.675
Right?

NOTE Confidence: 0.99918056

00:48:12.455 --> 00:48:13.675
Really good utility

NOTE Confidence: 0.94417

00:48:14.215 --> 00:48:15.515
that we're seeing here.

NOTE Confidence: 0.99491024

00:48:18.210 --> 00:48:19.270
Very good discriminatory

NOTE Confidence: 0.9407075

00:48:19.810 --> 00:48:21.250
capacity, and and this may

NOTE Confidence: 0.9407075

00:48:21.250 --> 00:48:22.150
be its greatest

NOTE Confidence: 0.9839914

00:48:22.770 --> 00:48:23.270
value.

NOTE Confidence: 0.9851559

00:48:23.570 --> 00:48:24.770
The assay has a good

NOTE Confidence: 0.9851559

00:48:24.770 --> 00:48:26.369
success rate from also getting

NOTE Confidence: 0.9851559

00:48:26.369 --> 00:48:27.109
the FFPBE

NOTE Confidence: 0.75912666

00:48:27.969 --> 00:48:28.469
tissue,

NOTE Confidence: 0.96229446

00:48:29.090 --> 00:48:31.265
and in these important categories

NOTE Confidence: 0.96229446

00:48:31.265 --> 00:48:32.545
here, this clinical 1b, but

NOTE Confidence: 0.96229446

00:48:32.545 --> 00:48:34.085
also in our older patients,

NOTE Confidence: 0.96229446

00:48:34.385 --> 00:48:36.145
where risks of general anesthesia,

NOTE Confidence: 0.96229446

00:48:36.145 --> 00:48:37.105
which you have to have

NOTE Confidence: 0.96229446

00:48:37.105 --> 00:48:38.145
to have a central note,

NOTE Confidence: 0.96229446

00:48:38.145 --> 00:48:38.885
are different.

NOTE Confidence: 0.99024254

00:48:39.265 --> 00:48:40.465
So in these in the

NOTE Confidence: 0.99024254

00:48:40.465 --> 00:48:41.905
patients that are low risk,

NOTE Confidence: 0.99024254

00:48:41.905 --> 00:48:43.780
again, six point six percent

NOTE Confidence: 0.99024254

00:48:43.780 --> 00:48:44.980
versus these patients that are

NOTE Confidence: 0.99024254

00:48:44.980 --> 00:48:45.480
being

NOTE Confidence: 0.9631238

00:48:45.780 --> 00:48:47.619
identified at high risk and

NOTE Confidence: 0.9631238

00:48:47.619 --> 00:48:49.140
where we're actually confirming that

NOTE Confidence: 0.9631238

00:48:49.140 --> 00:48:50.500
that's the case, I think

NOTE Confidence: 0.9631238

00:48:50.500 --> 00:48:51.859
that this is also a

NOTE Confidence: 0.9631238

00:48:51.859 --> 00:48:53.719
group that's pretty powerful.

NOTE Confidence: 0.9996333

00:48:56.695 --> 00:48:57.994
It's been validated

NOTE Confidence: 0.9788122

00:48:58.295 --> 00:48:59.974
independently now. This is a

NOTE Confidence: 0.9788122

00:48:59.974 --> 00:49:02.535
recent data from, a Dutch

NOTE Confidence: 0.9788122

00:49:02.535 --> 00:49:04.075
trial. Again, sensitivity

NOTE Confidence: 0.95878166

00:49:04.375 --> 00:49:05.895
about ninety two point five

NOTE Confidence: 0.95878166

00:49:05.895 --> 00:49:07.515
percent, a good negative

NOTE Confidence: 0.9599164

00:49:08.109 --> 00:49:09.630
predictive value at ninety four

NOTE Confidence: 0.9599164

00:49:09.630 --> 00:49:10.130
percent.

NOTE Confidence: 0.99623543

00:49:10.670 --> 00:49:11.570
Again, specifically

NOTE Confidence: 0.9639834

00:49:12.270 --> 00:49:13.710
at that group where we

NOTE Confidence: 0.9639834

00:49:13.710 --> 00:49:14.910
actually have a real gray

NOTE Confidence: 0.9639834

00:49:14.910 --> 00:49:16.369
area, where we have real

NOTE Confidence: 0.9639834

00:49:16.430 --> 00:49:18.450
focused conversations in the clinic.

NOTE Confidence: 0.9725479

00:49:18.829 --> 00:49:20.369
And, again, we see discrimination

NOTE Confidence: 0.97775537

00:49:20.750 --> 00:49:23.145
between the recurrence free, distant

NOTE Confidence: 0.97775537

00:49:23.145 --> 00:49:24.844
metastasis free, and the melanoma

NOTE Confidence: 0.97775537

00:49:24.985 --> 00:49:25.965
specific survival

NOTE Confidence: 0.9851365

00:49:26.505 --> 00:49:27.885
between these groups.

NOTE Confidence: 0.94693947

00:49:28.185 --> 00:49:30.425
Okay? And, again, the these

NOTE Confidence: 0.94693947

00:49:30.585 --> 00:49:31.885
as you draw them out,

NOTE Confidence: 0.99973106

00:49:32.425 --> 00:49:33.485
these are conversations

NOTE Confidence: 0.9766091

00:49:33.785 --> 00:49:34.825
that you wanna have with

NOTE Confidence: 0.9766091

00:49:34.825 --> 00:49:35.565
your patients,

NOTE Confidence: 0.99633396

00:49:35.880 --> 00:49:37.339
things that help us discriminate

NOTE Confidence: 0.99633396

00:49:37.559 --> 00:49:38.920
about what we're gonna do,

NOTE Confidence: 0.99633396

00:49:38.920 --> 00:49:40.599
what decisions that we're going

NOTE Confidence: 0.99633396

00:49:40.599 --> 00:49:41.260
to make.

NOTE Confidence: 0.93903846

00:49:44.200 --> 00:49:46.039
And and, again, this is,

NOTE Confidence: 0.79649186

00:49:46.599 --> 00:49:47.099
from,

NOTE Confidence: 0.90605193

00:49:48.535 --> 00:49:50.075
Yu et al, from, again,

NOTE Confidence: 0.90605193

00:49:50.215 --> 00:49:52.455
just recently published. Again, looking

NOTE Confidence: 0.90605193

00:49:52.455 --> 00:49:53.815
more specifically at t one

NOTE Confidence: 0.90605193

00:49:53.815 --> 00:49:55.515
a melanomas and graphically

NOTE Confidence: 0.9161053

00:49:56.055 --> 00:49:57.015
over here, you can see

NOTE Confidence: 0.9161053

00:49:57.015 --> 00:49:58.935
that the they're detecting some

NOTE Confidence: 0.9161053

00:49:58.935 --> 00:49:59.915
of these outliers,

NOTE Confidence: 0.9883878

00:50:00.670 --> 00:50:01.950
the very group of people

NOTE Confidence: 0.9883878

00:50:01.950 --> 00:50:03.150
that may have high risk

NOTE Confidence: 0.9883878

00:50:03.150 --> 00:50:04.590
features. Again, it's a low

NOTE Confidence: 0.9883878

00:50:04.590 --> 00:50:06.030
prevalence. It's a low group

NOTE Confidence: 0.9883878

00:50:06.030 --> 00:50:07.550
of patients. So, again, we'll

NOTE Confidence: 0.9883878

00:50:07.550 --> 00:50:08.590
all have to benefit the

NOTE Confidence: 0.9883878

00:50:08.590 --> 00:50:09.570
cost and benefit

NOTE Confidence: 0.9502234

00:50:09.950 --> 00:50:10.989
of that as well as

NOTE Confidence: 0.9502234

00:50:10.989 --> 00:50:11.950
when we think about if

NOTE Confidence: 0.9502234

00:50:11.950 --> 00:50:13.010
it's a low prevalence,

NOTE Confidence: 0.98272854

00:50:14.165 --> 00:50:15.364
you may have more false

NOTE Confidence: 0.98272854

00:50:15.364 --> 00:50:16.805
positives. Right? So a lot

NOTE Confidence: 0.98272854

00:50:16.805 --> 00:50:17.844
of this is focused on,

NOTE Confidence: 0.98272854

00:50:17.844 --> 00:50:18.724
you know, if it's a

NOTE Confidence: 0.98272854

00:50:18.724 --> 00:50:20.244
negative test, can you trust

NOTE Confidence: 0.98272854

00:50:20.244 --> 00:50:21.765
that? Right? So things that

NOTE Confidence: 0.98272854

00:50:21.765 --> 00:50:22.724
we all have to think

NOTE Confidence: 0.98272854

00:50:22.724 --> 00:50:23.605
about. And, again, a lot

NOTE Confidence: 0.98272854

00:50:23.605 --> 00:50:24.885
of this data, you could

NOTE Confidence: 0.98272854

00:50:24.885 --> 00:50:26.665
spend hours delving into.

NOTE Confidence: 0.9324816

00:50:27.540 --> 00:50:29.080
For head and neck populations

NOTE Confidence: 0.9324816

00:50:29.219 --> 00:50:30.820
where we worry about false

NOTE Confidence: 0.9324816

00:50:30.820 --> 00:50:32.660
negatives in sentinel nodes, that

NOTE Confidence: 0.9324816

00:50:32.660 --> 00:50:33.620
that rate is higher than

NOTE Confidence: 0.9324816

00:50:33.620 --> 00:50:34.260
what we have on the

NOTE Confidence: 0.9324816

00:50:34.260 --> 00:50:35.480
trunk and extremities,

NOTE Confidence: 0.8799142

00:50:36.100 --> 00:50:38.340
again, recent study just published,

NOTE Confidence: 0.8799142

00:50:38.340 --> 00:50:39.640
again, looking to validate,

NOTE Confidence: 0.8503565

00:50:40.580 --> 00:50:41.080
the

NOTE Confidence: 0.9393371

00:50:41.664 --> 00:50:42.244
the CPGP,

NOTE Confidence: 0.9957701

00:50:43.265 --> 00:50:44.885
again, seems to be

NOTE Confidence: 0.97598714

00:50:45.424 --> 00:50:46.944
none not different than what

NOTE Confidence: 0.97598714

00:50:46.944 --> 00:50:48.565
we're seeing in the extremities,

NOTE Confidence: 0.97598714

00:50:48.785 --> 00:50:49.924
which is really important.

NOTE Confidence: 0.99746346

00:50:52.545 --> 00:50:53.045
So

NOTE Confidence: 0.8791274

00:50:53.799 --> 00:50:54.839
when we're looking just for

NOTE Confidence: 0.8791274

00:50:54.839 --> 00:50:56.619
sentinel node and decision making,

NOTE Confidence: 0.9982626

00:50:56.920 --> 00:50:57.420
again,

NOTE Confidence: 0.9693978

00:50:57.799 --> 00:50:58.680
if we kind of look

NOTE Confidence: 0.9693978

00:50:58.680 --> 00:51:00.140
at things head to head,

NOTE Confidence: 0.9693978

00:51:00.359 --> 00:51:02.119
there's some benefits but detriments,

NOTE Confidence: 0.9693978

00:51:02.119 --> 00:51:03.079
I think, of each of

NOTE Confidence: 0.9693978

00:51:03.079 --> 00:51:04.599
the assays. The thirty one

NOTE Confidence: 0.9693978

00:51:04.599 --> 00:51:05.799
GEP and I thirty one

NOTE Confidence: 0.9693978

00:51:05.799 --> 00:51:07.260
GEP, which has been around

NOTE Confidence: 0.9693978

00:51:07.400 --> 00:51:08.140
the longest,

NOTE Confidence: 0.9940058

00:51:09.145 --> 00:51:10.665
you know, is not great

NOTE Confidence: 0.9940058

00:51:10.665 --> 00:51:11.405
at discriminating

NOTE Confidence: 0.9830752

00:51:11.945 --> 00:51:13.645
amongst that t one a

NOTE Confidence: 0.9830752

00:51:13.864 --> 00:51:14.364
category,

NOTE Confidence: 0.9994529

00:51:15.465 --> 00:51:17.245
where it hasn't been validated.

NOTE Confidence: 0.9734657

00:51:18.825 --> 00:51:19.325
There's

NOTE Confidence: 0.9583389

00:51:19.785 --> 00:51:20.985
with both of them, we're

NOTE Confidence: 0.9583389

00:51:20.985 --> 00:51:22.790
gonna see that there's decreasing

NOTE Confidence: 0.9583389

00:51:23.010 --> 00:51:24.450
the number of central lymph

NOTE Confidence: 0.9583389

00:51:24.450 --> 00:51:25.489
nodes in theory that we

NOTE Confidence: 0.9583389

00:51:25.489 --> 00:51:26.230
would perform.

NOTE Confidence: 0.9532217

00:51:27.090 --> 00:51:28.210
Almost all of this except

NOTE Confidence: 0.9532217

00:51:28.210 --> 00:51:29.030
for the DECIDE

NOTE Confidence: 0.99854416

00:51:29.410 --> 00:51:30.930
trial was also done only

NOTE Confidence: 0.99854416

00:51:30.930 --> 00:51:31.750
in retrospective

NOTE Confidence: 0.9716429

00:51:32.450 --> 00:51:34.150
series and really wasn't powerfully

NOTE Confidence: 0.9716429

00:51:34.210 --> 00:51:35.810
paired like the MERLIN trial

NOTE Confidence: 0.9716429

00:51:35.810 --> 00:51:37.110
was with that assay.

NOTE Confidence: 0.9533678

00:51:39.335 --> 00:51:40.775
And that really becomes the

NOTE Confidence: 0.9533678

00:51:40.775 --> 00:51:41.994
difference why that

NOTE Confidence: 0.98668104

00:51:42.614 --> 00:51:44.375
got the nod from the

NOTE Confidence: 0.98668104

00:51:44.375 --> 00:51:44.875
NCCN,

NOTE Confidence: 0.9992358

00:51:45.335 --> 00:51:47.015
just the number and the

NOTE Confidence: 0.9992358

00:51:47.015 --> 00:51:48.395
work that went into

NOTE Confidence: 0.9960144

00:51:48.855 --> 00:51:49.355
prospectively

NOTE Confidence: 0.8214377

00:51:49.815 --> 00:51:50.714
following this,

NOTE Confidence: 0.99961203

00:51:51.734 --> 00:51:52.234
internationally

NOTE Confidence: 0.98482203

00:51:53.060 --> 00:51:53.800
for this.

NOTE Confidence: 0.9955857

00:51:54.180 --> 00:51:54.680
Again,

NOTE Confidence: 0.9996631

00:51:55.060 --> 00:51:55.800
some important

NOTE Confidence: 0.9959878

00:51:56.180 --> 00:51:56.840
take homes

NOTE Confidence: 0.9437556

00:51:57.300 --> 00:51:58.660
to always think about with

NOTE Confidence: 0.9437556

00:51:58.660 --> 00:51:59.160
these.

NOTE Confidence: 0.99502635

00:51:59.619 --> 00:52:01.140
There is industry funding and

NOTE Confidence: 0.99502635

00:52:01.140 --> 00:52:01.640
authorship

NOTE Confidence: 0.93811464

00:52:02.020 --> 00:52:03.219
bias. Even the best of

NOTE Confidence: 0.93811464

00:52:03.219 --> 00:52:04.500
us when we when these

NOTE Confidence: 0.93811464

00:52:04.500 --> 00:52:05.859
are funded, there's a lot

NOTE Confidence: 0.93811464

00:52:05.859 --> 00:52:07.300
of input from these,

NOTE Confidence: 0.73558354

00:52:08.835 --> 00:52:09.335
particularly

NOTE Confidence: 0.9287799

00:52:09.635 --> 00:52:10.135
for

NOTE Confidence: 0.9343736

00:52:10.435 --> 00:52:11.094
the g,

NOTE Confidence: 0.91473883

00:52:11.475 --> 00:52:13.734
the, thirty one gene GP.

NOTE Confidence: 0.98173743

00:52:14.755 --> 00:52:15.715
A lot of the data,

NOTE Confidence: 0.98173743

00:52:15.715 --> 00:52:16.594
if you look at it,

NOTE Confidence: 0.98173743

00:52:16.594 --> 00:52:18.195
they've been republishing some of

NOTE Confidence: 0.98173743

00:52:18.195 --> 00:52:19.335
the similar datasets,

NOTE Confidence: 0.9330791

00:52:19.875 --> 00:52:21.635
and that's a practice that

NOTE Confidence: 0.9330791

00:52:21.635 --> 00:52:22.515
one has to be wary

NOTE Confidence: 0.9330791

00:52:22.515 --> 00:52:23.715
about. So it can it

NOTE Confidence: 0.9330791

00:52:23.715 --> 00:52:24.375
can almost

NOTE Confidence: 0.93104756

00:52:25.340 --> 00:52:26.540
the value of that because

NOTE Confidence: 0.93104756

00:52:26.540 --> 00:52:27.580
if you're publishing on the

NOTE Confidence: 0.93104756

00:52:27.580 --> 00:52:29.420
same data and including some

NOTE Confidence: 0.93104756

00:52:29.420 --> 00:52:30.460
and the other, it just

NOTE Confidence: 0.93104756

00:52:30.460 --> 00:52:31.660
becomes really tricky when you're

NOTE Confidence: 0.93104756

00:52:31.660 --> 00:52:32.700
actually trying to go through

NOTE Confidence: 0.93104756

00:52:32.700 --> 00:52:33.360
the literature.

NOTE Confidence: 0.9424467

00:52:34.540 --> 00:52:36.780
Again, the primary objective technically

NOTE Confidence: 0.9424467

00:52:36.780 --> 00:52:37.980
wasn't met in the Merlin

NOTE Confidence: 0.9424467

00:52:37.980 --> 00:52:38.864
o o one,

NOTE Confidence: 0.9698401

00:52:39.585 --> 00:52:40.864
and and that was a

NOTE Confidence: 0.9698401

00:52:40.864 --> 00:52:42.385
higher than expected rate, and

NOTE Confidence: 0.9698401

00:52:42.385 --> 00:52:44.165
the the low risk not

NOTE Confidence: 0.9698401

00:52:44.225 --> 00:52:45.905
keeping that below that five

NOTE Confidence: 0.9698401

00:52:45.905 --> 00:52:47.905
percent threshold that we've tried

NOTE Confidence: 0.9698401

00:52:47.905 --> 00:52:49.505
to, you know, carve out

NOTE Confidence: 0.9698401

00:52:49.505 --> 00:52:50.725
as when we should consider

NOTE Confidence: 0.9698401

00:52:50.864 --> 00:52:52.145
doing it. So seven point

NOTE Confidence: 0.9698401

00:52:52.145 --> 00:52:53.529
one, is a little bit

NOTE Confidence: 0.9698401

00:52:53.529 --> 00:52:54.730
higher than what they what

NOTE Confidence: 0.9698401

00:52:54.730 --> 00:52:55.950
they thought would be.

NOTE Confidence: 0.968741

00:52:58.089 --> 00:53:00.170
There's no survival benefit. It's

NOTE Confidence: 0.968741

00:53:00.170 --> 00:53:01.529
not paired yet. Again, a

NOTE Confidence: 0.968741

00:53:01.529 --> 00:53:02.250
little bit out of the

NOTE Confidence: 0.968741

00:53:02.250 --> 00:53:03.849
scope of the conversation. Again,

NOTE Confidence: 0.968741

00:53:03.849 --> 00:53:05.789
we talked about largely retrospective

NOTE Confidence: 0.968741

00:53:06.010 --> 00:53:07.210
with the exception of the

NOTE Confidence: 0.968741

00:53:07.210 --> 00:53:08.190
Merlin trial.

NOTE Confidence: 0.9108334

00:53:08.945 --> 00:53:09.445
Again,

NOTE Confidence: 0.9693574

00:53:09.905 --> 00:53:11.205
really needs to discriminate

NOTE Confidence: 0.96432626

00:53:11.665 --> 00:53:12.705
the very groups that we

NOTE Confidence: 0.96432626

00:53:12.705 --> 00:53:13.665
wanna use them. And if

NOTE Confidence: 0.96432626

00:53:13.665 --> 00:53:14.864
someone wants to use a

NOTE Confidence: 0.96432626

00:53:14.864 --> 00:53:16.545
study, the threshold has to

NOTE Confidence: 0.96432626

00:53:16.545 --> 00:53:18.225
be really high and how

NOTE Confidence: 0.96432626

00:53:18.225 --> 00:53:19.185
well this is gonna be

NOTE Confidence: 0.96432626

00:53:19.185 --> 00:53:20.545
to justify the cost that

NOTE Confidence: 0.96432626

00:53:20.545 --> 00:53:21.445
it would potentially

NOTE Confidence: 0.9935105

00:53:21.745 --> 00:53:22.245
be.

NOTE Confidence: 0.96808034

00:53:22.785 --> 00:53:23.960
And I think that, you

NOTE Confidence: 0.96808034

00:53:23.960 --> 00:53:24.839
know, I alluded to it

NOTE Confidence: 0.96808034

00:53:24.839 --> 00:53:25.900
a little bit earlier,

NOTE Confidence: 0.99100107

00:53:26.359 --> 00:53:27.500
there's high pulse

NOTE Confidence: 0.9903671

00:53:28.039 --> 00:53:29.319
false positive rates. And the

NOTE Confidence: 0.9903671

00:53:29.319 --> 00:53:30.359
very first time that I

NOTE Confidence: 0.9903671

00:53:30.359 --> 00:53:31.400
ever saw a patient come

NOTE Confidence: 0.9903671

00:53:31.400 --> 00:53:32.219
into clinic

NOTE Confidence: 0.97610676

00:53:32.839 --> 00:53:33.799
was when I was a

NOTE Confidence: 0.97610676

00:53:33.799 --> 00:53:35.339
fellow in twenty fourteen,

NOTE Confidence: 0.99958944

00:53:35.799 --> 00:53:37.000
and a woman was three

NOTE Confidence: 0.99958944

00:53:37.000 --> 00:53:37.900
months postpartum

NOTE Confidence: 0.98337996

00:53:38.495 --> 00:53:39.535
and had had a one

NOTE Confidence: 0.98337996

00:53:39.535 --> 00:53:41.635
point eight millimeter non ulcerated

NOTE Confidence: 0.9909225

00:53:42.094 --> 00:53:44.015
nodular melanoma with a negative

NOTE Confidence: 0.9909225

00:53:44.015 --> 00:53:45.935
sentinel node and walked into

NOTE Confidence: 0.9909225

00:53:45.935 --> 00:53:47.614
clinic with a class two

NOTE Confidence: 0.9909225

00:53:47.614 --> 00:53:48.114
result

NOTE Confidence: 0.9791305

00:53:48.575 --> 00:53:49.555
on her GEP.

NOTE Confidence: 0.9887555

00:53:50.735 --> 00:53:51.235
And

NOTE Confidence: 0.99978113

00:53:52.200 --> 00:53:52.859
we were

NOTE Confidence: 0.9698353

00:53:53.160 --> 00:53:54.440
at a loss about what

NOTE Confidence: 0.9698353

00:53:54.440 --> 00:53:55.339
do we do.

NOTE Confidence: 0.96098846

00:53:55.960 --> 00:53:57.580
Again, I I thankfully graduated

NOTE Confidence: 0.96098846

00:53:57.640 --> 00:53:58.880
from fellowship, but I I

NOTE Confidence: 0.96098846

00:53:58.880 --> 00:54:00.040
I do think about and

NOTE Confidence: 0.96098846

00:54:00.040 --> 00:54:00.700
I wonder

NOTE Confidence: 0.9450658

00:54:01.160 --> 00:54:03.080
about this young woman who

NOTE Confidence: 0.9450658

00:54:03.080 --> 00:54:04.359
was thirty eight years old

NOTE Confidence: 0.9450658

00:54:04.359 --> 00:54:05.239
who had come into the

NOTE Confidence: 0.9450658

00:54:05.239 --> 00:54:05.739
clinic.

NOTE Confidence: 0.9988256

00:54:06.200 --> 00:54:06.700
And

NOTE Confidence: 0.999629

00:54:07.305 --> 00:54:08.045
that psychological

NOTE Confidence: 0.99767035

00:54:08.825 --> 00:54:10.525
cost was something that has

NOTE Confidence: 0.999818

00:54:10.905 --> 00:54:11.805
stuck with me

NOTE Confidence: 0.99973696

00:54:12.265 --> 00:54:13.645
for the last

NOTE Confidence: 0.9999285

00:54:14.105 --> 00:54:14.605
decade

NOTE Confidence: 0.95120096

00:54:15.065 --> 00:54:16.364
about just seeing

NOTE Confidence: 0.99753267

00:54:16.744 --> 00:54:17.944
what the cost is to

NOTE Confidence: 0.99753267

00:54:17.944 --> 00:54:18.605
our patients

NOTE Confidence: 0.9841633

00:54:19.065 --> 00:54:20.025
if they have a false

NOTE Confidence: 0.9841633

00:54:20.025 --> 00:54:21.704
positive. It's nice, you know,

NOTE Confidence: 0.9841633

00:54:21.704 --> 00:54:23.360
to have a really good

NOTE Confidence: 0.9841633

00:54:23.360 --> 00:54:25.040
negative predictive value and say,

NOTE Confidence: 0.9841633

00:54:25.040 --> 00:54:26.239
okay. If it's negative, you're

NOTE Confidence: 0.9841633

00:54:26.239 --> 00:54:26.739
good.

NOTE Confidence: 0.9989581

00:54:27.600 --> 00:54:29.700
But when we're not really

NOTE Confidence: 0.9565363

00:54:30.239 --> 00:54:32.020
capturing or we're causing undue

NOTE Confidence: 0.9565363

00:54:32.160 --> 00:54:34.160
cost to patients, and like

NOTE Confidence: 0.9565363

00:54:34.160 --> 00:54:35.200
I said, it's not just

NOTE Confidence: 0.9565363

00:54:35.200 --> 00:54:35.700
about

NOTE Confidence: 0.96691686

00:54:36.055 --> 00:54:37.335
screening and so forth, it's

NOTE Confidence: 0.96691686

00:54:37.335 --> 00:54:38.215
also about what does it

NOTE Confidence: 0.96691686

00:54:38.215 --> 00:54:39.675
do to them, again,

NOTE Confidence: 0.9854804

00:54:40.135 --> 00:54:41.255
we need to be really,

NOTE Confidence: 0.9854804

00:54:41.255 --> 00:54:43.015
really thoughtful about that. And

NOTE Confidence: 0.9854804

00:54:43.015 --> 00:54:44.155
and, again, just

NOTE Confidence: 0.98552114

00:54:44.455 --> 00:54:45.975
echoing all of my colleagues,

NOTE Confidence: 0.98552114

00:54:45.975 --> 00:54:46.635
you know,

NOTE Confidence: 0.90484285

00:54:46.935 --> 00:54:48.475
GEP, I think it really

NOTE Confidence: 0.99795705

00:54:48.840 --> 00:54:51.080
should inform shared decision making.

NOTE Confidence: 0.99795705

00:54:51.080 --> 00:54:52.220
It doesn't replace

NOTE Confidence: 0.9993819

00:54:52.600 --> 00:54:53.340
the conversations

NOTE Confidence: 0.9918661

00:54:53.640 --> 00:54:55.580
that we have and continued

NOTE Confidence: 0.9918661

00:54:55.720 --> 00:54:56.860
thoughtful interaction

NOTE Confidence: 0.9917907

00:54:57.640 --> 00:54:59.560
or replace the other tools

NOTE Confidence: 0.9917907

00:54:59.560 --> 00:55:00.460
that we have.

NOTE Confidence: 0.99646044

00:55:01.640 --> 00:55:02.920
So with that, I will

NOTE Confidence: 0.99646044

00:55:02.920 --> 00:55:03.820
I will close.

NOTE Confidence: 0.9281211

00:55:06.494 --> 00:55:07.635
Stop my share.

NOTE Confidence: 0.94955707

00:55:14.895 --> 00:55:15.714
Sorry, guys.

NOTE Confidence: 0.9897847

00:55:16.015 --> 00:55:17.855
Can't stop sharing. Oh, there

NOTE Confidence: 0.9897847

00:55:17.855 --> 00:55:18.435
it is.

NOTE Confidence: 0.99712354

00:55:19.239 --> 00:55:21.340
Thanks, Kelly. That was great.

NOTE Confidence: 0.9973436

00:55:22.760 --> 00:55:24.680
So I am up next.

NOTE Confidence: 0.9973436

00:55:24.680 --> 00:55:25.480
Let me see if I

NOTE Confidence: 0.9973436

00:55:25.480 --> 00:55:26.860
can figure out the

NOTE Confidence: 0.99963707

00:55:27.480 --> 00:55:29.180
sharing process here.

NOTE Confidence: 0.99976563

00:55:32.154 --> 00:55:33.055
Okay. Great.

NOTE Confidence: 0.9493399

00:55:33.914 --> 00:55:35.594
So I'm Sean Christiansen. I'm

NOTE Confidence: 0.9493399

00:55:35.594 --> 00:55:36.255
a dermatologist

NOTE Confidence: 0.98132855

00:55:36.635 --> 00:55:38.234
and Mohs surgeon, and I'm

NOTE Confidence: 0.98132855

00:55:38.234 --> 00:55:39.994
gonna shift gears slightly. And

NOTE Confidence: 0.98132855

00:55:39.994 --> 00:55:41.614
instead of giving an overview

NOTE Confidence: 0.98132855

00:55:41.914 --> 00:55:43.674
of GEPs, I'm gonna focus

NOTE Confidence: 0.98132855

00:55:43.674 --> 00:55:44.894
on one

NOTE Confidence: 0.9997823

00:55:45.270 --> 00:55:46.489
specific utilization

NOTE Confidence: 0.9980023

00:55:46.870 --> 00:55:47.690
of GEP,

NOTE Confidence: 0.9319632

00:55:48.150 --> 00:55:49.350
in a clinical trial, which

NOTE Confidence: 0.9319632

00:55:49.350 --> 00:55:50.469
is the ICEFAN trial, which

NOTE Confidence: 0.9319632

00:55:50.469 --> 00:55:51.690
I'll get to talk about,

NOTE Confidence: 0.95764875

00:55:52.070 --> 00:55:53.290
in just a couple minutes.

NOTE Confidence: 0.98894846

00:55:53.830 --> 00:55:55.050
So these are my disclosures,

NOTE Confidence: 0.98894846

00:55:55.110 --> 00:55:56.310
and they're not relevant to

NOTE Confidence: 0.98894846

00:55:56.310 --> 00:55:57.510
what I'm talking about today

NOTE Confidence: 0.98894846

00:55:57.510 --> 00:55:58.965
except for the last one.

NOTE Confidence: 0.996517

00:55:59.445 --> 00:56:00.405
I I will be an

NOTE Confidence: 0.996517

00:56:00.405 --> 00:56:00.905
investigator,

NOTE Confidence: 0.97224075

00:56:02.005 --> 00:56:03.364
on the the trial, which

NOTE Confidence: 0.97224075

00:56:03.364 --> 00:56:04.905
is sponsored by Skyline

NOTE Confidence: 0.99119955

00:56:05.205 --> 00:56:05.705
Diagnostics,

NOTE Confidence: 0.9880788

00:56:06.245 --> 00:56:07.364
the company that makes the

NOTE Confidence: 0.9880788

00:56:07.364 --> 00:56:07.864
Merlin

NOTE Confidence: 0.998566

00:56:08.245 --> 00:56:08.745
GEP.

NOTE Confidence: 0.99648863

00:56:10.245 --> 00:56:11.364
So I'll talk first about

NOTE Confidence: 0.99648863

00:56:11.364 --> 00:56:13.045
principles of surgical management of

NOTE Confidence: 0.99648863

00:56:13.045 --> 00:56:14.105
localized melanoma.

NOTE Confidence: 0.9795777

00:56:14.645 --> 00:56:15.880
I'm gonna take a slight

NOTE Confidence: 0.9795777

00:56:15.880 --> 00:56:17.820
tangent to focus on pathologic

NOTE Confidence: 0.9795777

00:56:17.960 --> 00:56:19.480
margin analysis and why that's

NOTE Confidence: 0.9795777

00:56:19.480 --> 00:56:19.980
important.

NOTE Confidence: 0.9989745

00:56:20.600 --> 00:56:21.719
And then we'll talk about

NOTE Confidence: 0.9989745

00:56:21.719 --> 00:56:23.180
how we can use GEP

NOTE Confidence: 0.9899709

00:56:23.640 --> 00:56:25.180
for predicting nodal metastasis

NOTE Confidence: 0.96002704

00:56:25.480 --> 00:56:26.920
risk and how that influences

NOTE Confidence: 0.96002704

00:56:26.920 --> 00:56:28.540
our decision making and treatment.

NOTE Confidence: 0.9977858

00:56:29.195 --> 00:56:30.075
And then I'll tell you

NOTE Confidence: 0.9977858

00:56:30.075 --> 00:56:31.295
about the the trial,

NOTE Confidence: 0.9631939

00:56:31.675 --> 00:56:32.955
that we're starting up at

NOTE Confidence: 0.9631939

00:56:32.955 --> 00:56:34.975
Yale, hopefully, sometime soon.

NOTE Confidence: 0.9948324

00:56:36.075 --> 00:56:38.155
So surgical management is really

NOTE Confidence: 0.9948324

00:56:38.155 --> 00:56:39.755
the primary treatment for localized

NOTE Confidence: 0.9948324

00:56:39.755 --> 00:56:41.055
and early stage melanoma.

NOTE Confidence: 0.97654563

00:56:41.594 --> 00:56:42.875
And just to review, the

NOTE Confidence: 0.97654563

00:56:42.875 --> 00:56:44.610
goals of surgical excision are

NOTE Confidence: 0.97654563

00:56:44.610 --> 00:56:46.290
are to accurately stage the

NOTE Confidence: 0.97654563

00:56:46.290 --> 00:56:47.890
tumor, which is just as

NOTE Confidence: 0.97654563

00:56:47.890 --> 00:56:49.090
important now as it ever

NOTE Confidence: 0.97654563

00:56:49.090 --> 00:56:50.790
was, especially in the era

NOTE Confidence: 0.97654563

00:56:50.850 --> 00:56:52.630
of targeted therapy and immunotherapy.

NOTE Confidence: 0.98236716

00:56:52.930 --> 00:56:53.890
We we really need to

NOTE Confidence: 0.98236716

00:56:53.890 --> 00:56:55.250
know what the risk factors

NOTE Confidence: 0.98236716

00:56:55.250 --> 00:56:56.470
are to make those decisions.

NOTE Confidence: 0.9973288

00:56:57.330 --> 00:56:58.850
We also wanna optimize local

NOTE Confidence: 0.9973288

00:56:58.850 --> 00:57:00.725
control by achieving complete tumor

NOTE Confidence: 0.9973288

00:57:00.725 --> 00:57:01.225
removal

NOTE Confidence: 0.98988634

00:57:01.525 --> 00:57:03.385
while balancing that with optimizing

NOTE Confidence: 0.98988634

00:57:03.605 --> 00:57:05.445
functional and cosmetic outcomes from

NOTE Confidence: 0.98988634

00:57:05.445 --> 00:57:05.945
surgery.

NOTE Confidence: 0.99219

00:57:06.325 --> 00:57:08.005
And about fifty years ago,

NOTE Confidence: 0.99219

00:57:08.005 --> 00:57:09.125
the trend was to really

NOTE Confidence: 0.99219

00:57:09.125 --> 00:57:10.085
just take as wide of

NOTE Confidence: 0.99219

00:57:10.085 --> 00:57:11.305
a margin as possible.

NOTE Confidence: 0.97227764

00:57:12.020 --> 00:57:13.140
But since then, we've had

NOTE Confidence: 0.97227764

00:57:13.140 --> 00:57:14.420
some trials that have shown

NOTE Confidence: 0.97227764

00:57:14.420 --> 00:57:16.099
that wider surgical margins are

NOTE Confidence: 0.97227764

00:57:16.099 --> 00:57:17.400
not necessarily better.

NOTE Confidence: 0.97202057

00:57:18.020 --> 00:57:19.619
So a large trial sponsored

NOTE Confidence: 0.97202057

00:57:19.619 --> 00:57:20.520
by the WHO,

NOTE Confidence: 0.9798589

00:57:21.619 --> 00:57:23.745
showed that one centimeter versus

NOTE Confidence: 0.9798589

00:57:23.825 --> 00:57:25.745
three centimeter excision margins for

NOTE Confidence: 0.9798589

00:57:25.745 --> 00:57:27.425
melanoma less than two millimeters

NOTE Confidence: 0.9798589

00:57:27.425 --> 00:57:27.925
in-depth,

NOTE Confidence: 0.99896234

00:57:28.545 --> 00:57:29.745
there was no difference in

NOTE Confidence: 0.99896234

00:57:29.745 --> 00:57:30.805
disease free survival.

NOTE Confidence: 0.90177983

00:57:31.425 --> 00:57:32.465
And then later on in

NOTE Confidence: 0.90177983

00:57:32.465 --> 00:57:33.365
another trial,

NOTE Confidence: 0.9312069

00:57:34.065 --> 00:57:35.825
a deeper melanoma greater than

NOTE Confidence: 0.9312069

00:57:35.825 --> 00:57:37.350
two millimeters in-depth showed that

NOTE Confidence: 0.9312069

00:57:37.430 --> 00:57:38.250
two centimeters

NOTE Confidence: 0.97511977

00:57:38.630 --> 00:57:40.070
was not inferior to four

NOTE Confidence: 0.97511977

00:57:40.070 --> 00:57:41.530
centimeters. So there's a trend

NOTE Confidence: 0.97511977

00:57:41.670 --> 00:57:43.270
for us taking narrower margins,

NOTE Confidence: 0.97511977

00:57:43.270 --> 00:57:44.790
which can still be curative

NOTE Confidence: 0.97511977

00:57:44.790 --> 00:57:45.530
for melanoma.

NOTE Confidence: 0.93923974

00:57:46.070 --> 00:57:47.350
And the question is how

NOTE Confidence: 0.93923974

00:57:47.350 --> 00:57:48.650
narrow can we go?

NOTE Confidence: 0.9997492

00:57:49.270 --> 00:57:50.870
Before we answer that question,

NOTE Confidence: 0.9997492

00:57:50.870 --> 00:57:52.010
we have to recognize

NOTE Confidence: 0.96992046

00:57:52.315 --> 00:57:53.995
that skin cancer often does

NOTE Confidence: 0.96992046

00:57:53.995 --> 00:57:55.855
has have irregular extension.

NOTE Confidence: 0.96109235

00:57:56.395 --> 00:57:57.275
So this is something that

NOTE Confidence: 0.96109235

00:57:57.275 --> 00:57:58.715
came out of a, a

NOTE Confidence: 0.96109235

00:57:58.715 --> 00:58:00.155
publication in Annals of Plastic

NOTE Confidence: 0.96109235

00:58:00.155 --> 00:58:01.915
Surgery many years ago. They

NOTE Confidence: 0.96109235

00:58:01.915 --> 00:58:04.095
actually mapped out the three-dimensional

NOTE Confidence: 0.9710892

00:58:04.555 --> 00:58:05.835
extension of the skin cancer,

NOTE Confidence: 0.9710892

00:58:05.835 --> 00:58:06.555
and you can see how

NOTE Confidence: 0.9710892

00:58:06.555 --> 00:58:07.530
it has many of these

NOTE Confidence: 0.9710892

00:58:07.770 --> 00:58:08.270
irregular

NOTE Confidence: 0.9902586

00:58:08.890 --> 00:58:10.010
strands that penetrate through the

NOTE Confidence: 0.9902586

00:58:10.010 --> 00:58:11.230
subcutaneous tissue.

NOTE Confidence: 0.99375933

00:58:11.530 --> 00:58:13.370
And these irregular and occult

NOTE Confidence: 0.99375933

00:58:13.370 --> 00:58:15.130
islands of tumor may not

NOTE Confidence: 0.99375933

00:58:15.130 --> 00:58:17.150
be detected with standard histologic

NOTE Confidence: 0.99375933

00:58:17.370 --> 00:58:17.870
sections.

NOTE Confidence: 0.9994108

00:58:18.730 --> 00:58:19.770
So this is why the

NOTE Confidence: 0.9994108

00:58:19.770 --> 00:58:21.130
way that we process things

NOTE Confidence: 0.9994108

00:58:21.130 --> 00:58:22.270
is actually really important.

NOTE Confidence: 0.86139446

00:58:22.765 --> 00:58:23.744
So with standard,

NOTE Confidence: 0.95068324

00:58:24.205 --> 00:58:26.145
perpendicular or bread loaf sections,

NOTE Confidence: 0.99443895

00:58:26.605 --> 00:58:28.705
an elliptical specimen like this

NOTE Confidence: 0.99443895

00:58:28.845 --> 00:58:30.305
is cut into these perpendicular

NOTE Confidence: 0.99443895

00:58:30.525 --> 00:58:32.045
slices. Right? So we're only

NOTE Confidence: 0.99443895

00:58:32.045 --> 00:58:33.165
looking at the areas where

NOTE Confidence: 0.99443895

00:58:33.165 --> 00:58:34.380
we happen to take slices.

NOTE Confidence: 0.99113876

00:58:34.779 --> 00:58:36.059
And if there is one

NOTE Confidence: 0.99113876

00:58:36.059 --> 00:58:37.180
focal area that has a

NOTE Confidence: 0.99113876

00:58:37.180 --> 00:58:38.799
positive margin with an irregular

NOTE Confidence: 0.99113876

00:58:38.859 --> 00:58:39.359
extension,

NOTE Confidence: 0.9982718

00:58:39.740 --> 00:58:41.180
that might not be captured

NOTE Confidence: 0.9982718

00:58:41.180 --> 00:58:42.720
on these representative sections.

NOTE Confidence: 0.96924734

00:58:43.259 --> 00:58:44.779
In contrast, if we use

NOTE Confidence: 0.96924734

00:58:44.779 --> 00:58:46.380
en face sections with complete

NOTE Confidence: 0.96924734

00:58:46.380 --> 00:58:47.900
margin analysis, we're looking at

NOTE Confidence: 0.96924734

00:58:47.900 --> 00:58:49.660
the entire peripheral and deep

NOTE Confidence: 0.96924734

00:58:49.660 --> 00:58:50.160
margin.

NOTE Confidence: 0.9997665

00:58:50.475 --> 00:58:51.855
So any small area

NOTE Confidence: 0.9764842

00:58:52.235 --> 00:58:53.935
of positivity at the margin

NOTE Confidence: 0.9764842

00:58:54.075 --> 00:58:55.615
would, in fact, be detected.

NOTE Confidence: 0.9708754

00:58:56.235 --> 00:58:57.215
And this is the principle

NOTE Confidence: 0.9708754

00:58:57.275 --> 00:58:59.375
behind Mohs skin cancer surgery.

NOTE Confidence: 0.97053987

00:58:59.675 --> 00:59:00.875
Just to review this very,

NOTE Confidence: 0.97053987

00:59:00.875 --> 00:59:02.315
very briefly, this is a

NOTE Confidence: 0.97053987

00:59:02.315 --> 00:59:04.075
staged excision of skin cancer

NOTE Confidence: 0.97053987

00:59:04.075 --> 00:59:04.895
with intraoperative

NOTE Confidence: 0.99917346

00:59:05.195 --> 00:59:06.095
frozen sections

NOTE Confidence: 0.9973686

00:59:06.600 --> 00:59:08.600
examining the complete surgical margin,

NOTE Confidence: 0.9973686

00:59:08.760 --> 00:59:09.560
which are read by the

NOTE Confidence: 0.9973686

00:59:09.560 --> 00:59:10.700
surgeon as pathologist.

NOTE Confidence: 0.9879041

00:59:11.720 --> 00:59:13.160
And it's mostly used for

NOTE Confidence: 0.9879041

00:59:13.160 --> 00:59:14.860
basal and squamous cell carcinoma.

NOTE Confidence: 0.97265947

00:59:15.160 --> 00:59:16.440
It has not traditionally been

NOTE Confidence: 0.97265947

00:59:16.440 --> 00:59:17.340
used for melanoma

NOTE Confidence: 0.98951995

00:59:17.800 --> 00:59:19.320
because it has traditionally been

NOTE Confidence: 0.98951995

00:59:19.320 --> 00:59:20.060
more difficult

NOTE Confidence: 0.99481946

00:59:20.440 --> 00:59:22.665
to identify melanoma on frozen

NOTE Confidence: 0.99481946

00:59:22.665 --> 00:59:23.165
sections.

NOTE Confidence: 0.97306347

00:59:23.945 --> 00:59:25.545
But recently, that has slightly

NOTE Confidence: 0.97306347

00:59:25.545 --> 00:59:26.045
changed.

NOTE Confidence: 0.8772692

00:59:27.145 --> 00:59:28.265
So now we can actually

NOTE Confidence: 0.8772692

00:59:28.265 --> 00:59:29.385
use Mart one or melan

NOTE Confidence: 0.8772692

00:59:29.385 --> 00:59:30.125
a immunostains

NOTE Confidence: 0.9996472

00:59:30.665 --> 00:59:32.265
on frozen sections to identify

NOTE Confidence: 0.9996472

00:59:32.265 --> 00:59:32.765
melanocytes.

NOTE Confidence: 0.97497195

00:59:33.300 --> 00:59:35.220
So, these two images here

NOTE Confidence: 0.97497195

00:59:35.220 --> 00:59:36.820
are frozen sections of skin.

NOTE Confidence: 0.97497195

00:59:36.820 --> 00:59:37.780
One of them is a

NOTE Confidence: 0.97497195

00:59:37.780 --> 00:59:39.380
floor example of melanoma in

NOTE Confidence: 0.97497195

00:59:39.380 --> 00:59:40.820
situ. The other one is

NOTE Confidence: 0.97497195

00:59:40.820 --> 00:59:42.100
normal skin with some freeze

NOTE Confidence: 0.97497195

00:59:42.100 --> 00:59:42.600
artifact.

NOTE Confidence: 0.9892769

00:59:42.900 --> 00:59:44.420
Any pathologist in the audience

NOTE Confidence: 0.9892769

00:59:44.420 --> 00:59:45.940
will immediately recognize that it's

NOTE Confidence: 0.9892769

00:59:45.940 --> 00:59:46.740
the one on the left

NOTE Confidence: 0.9892769

00:59:46.740 --> 00:59:47.480
that's melanoma.

NOTE Confidence: 0.9910456

00:59:48.085 --> 00:59:48.805
But for the rest of

NOTE Confidence: 0.9910456

00:59:48.805 --> 00:59:49.765
us, it really helps to

NOTE Confidence: 0.9910456

00:59:49.765 --> 00:59:50.665
have the immunostain.

NOTE Confidence: 0.9798034

00:59:51.205 --> 00:59:52.505
So by using this immunostain,

NOTE Confidence: 0.9798034

00:59:52.645 --> 00:59:53.925
we can clearly see there's

NOTE Confidence: 0.9798034

00:59:53.925 --> 00:59:56.005
confluence, there's nesting, there's upward

NOTE Confidence: 0.9798034

00:59:56.005 --> 00:59:57.445
scatter of melanocytes in the

NOTE Confidence: 0.9798034

00:59:57.445 --> 00:59:59.125
melanoma in situ. But in

NOTE Confidence: 0.9798034

00:59:59.125 --> 01:00:00.245
normal skin, we just see

NOTE Confidence: 0.9798034

01:00:00.245 --> 01:00:01.145
a normal distribution.

NOTE Confidence: 0.9627502

01:00:02.600 --> 01:00:03.800
And a dual center study

NOTE Confidence: 0.9627502

01:00:03.800 --> 01:00:04.920
found that there's very high

NOTE Confidence: 0.9627502

01:00:04.920 --> 01:00:06.600
concordance between most sections and

NOTE Confidence: 0.9627502

01:00:06.600 --> 01:00:08.940
permanent pathology when using immunostains

NOTE Confidence: 0.9627502

01:00:09.160 --> 01:00:09.800
to detect,

NOTE Confidence: 0.9999092

01:00:10.200 --> 01:00:10.700
melanoma.

NOTE Confidence: 0.9869756

01:00:11.240 --> 01:00:12.680
So, at Yale, we've actually

NOTE Confidence: 0.9869756

01:00:12.680 --> 01:00:13.480
been doing this for a

NOTE Confidence: 0.9869756

01:00:13.480 --> 01:00:15.340
few years now. Mostly melanoma

NOTE Confidence: 0.9869756

01:00:15.400 --> 01:00:16.440
in situ, but a few

NOTE Confidence: 0.9869756

01:00:16.440 --> 01:00:18.365
superficially invasive melanoma cases.

NOTE Confidence: 0.9702179

01:00:18.745 --> 01:00:19.625
So this is a woman

NOTE Confidence: 0.9702179

01:00:19.625 --> 01:00:20.825
with a melanoma in situ

NOTE Confidence: 0.9702179

01:00:20.825 --> 01:00:22.585
in a very cosmetically sensitive

NOTE Confidence: 0.9702179

01:00:22.585 --> 01:00:23.865
location on the nose. And

NOTE Confidence: 0.9702179

01:00:23.865 --> 01:00:24.745
so we wanna try and

NOTE Confidence: 0.9702179

01:00:24.745 --> 01:00:25.625
take as narrow of a

NOTE Confidence: 0.9702179

01:00:25.625 --> 01:00:27.225
margin as possible. So I

NOTE Confidence: 0.9702179

01:00:27.225 --> 01:00:28.345
ended up taking a a

NOTE Confidence: 0.9702179

01:00:28.345 --> 01:00:29.945
four millimeter margin around this

NOTE Confidence: 0.9702179

01:00:29.945 --> 01:00:30.445
initially.

NOTE Confidence: 0.9563027

01:00:31.210 --> 01:00:32.490
And the area in red

NOTE Confidence: 0.9563027

01:00:32.490 --> 01:00:33.530
is where I processed a

NOTE Confidence: 0.9563027

01:00:33.530 --> 01:00:34.890
deep bulk specimen just to

NOTE Confidence: 0.9563027

01:00:34.890 --> 01:00:35.530
look at that and make

NOTE Confidence: 0.9563027

01:00:35.530 --> 01:00:36.890
sure there was no invasive

NOTE Confidence: 0.9563027

01:00:36.890 --> 01:00:37.390
tumor.

NOTE Confidence: 0.9694353

01:00:37.770 --> 01:00:38.810
There was, in fact, just

NOTE Confidence: 0.9694353

01:00:38.810 --> 01:00:40.250
melanoma in situ that was

NOTE Confidence: 0.9694353

01:00:40.250 --> 01:00:40.750
present.

NOTE Confidence: 0.9953115

01:00:41.130 --> 01:00:42.590
But on that first layer,

NOTE Confidence: 0.9953115

01:00:42.810 --> 01:00:44.250
there was a positive margin

NOTE Confidence: 0.9953115

01:00:44.250 --> 01:00:46.010
at the superior edge only.

NOTE Confidence: 0.9953115

01:00:46.010 --> 01:00:47.065
So I then was able

NOTE Confidence: 0.9953115

01:00:47.065 --> 01:00:48.425
to take an additional stage

NOTE Confidence: 0.9953115

01:00:48.425 --> 01:00:49.165
from there,

NOTE Confidence: 0.9670646

01:00:49.545 --> 01:00:50.685
which was clear.

NOTE Confidence: 0.9927241

01:00:51.225 --> 01:00:52.185
And this was the patient's

NOTE Confidence: 0.9927241

01:00:52.185 --> 01:00:53.785
defect in the end. So

NOTE Confidence: 0.9927241

01:00:53.785 --> 01:00:55.705
in the area inferiorly towards

NOTE Confidence: 0.9927241

01:00:55.705 --> 01:00:56.665
the alar rim, I was

NOTE Confidence: 0.9927241

01:00:56.665 --> 01:00:57.785
actually able to take a

NOTE Confidence: 0.9927241

01:00:57.785 --> 01:00:59.079
narrower margin than what is

NOTE Confidence: 0.9927241

01:00:59.079 --> 01:01:00.380
recommended by the NCCN.

NOTE Confidence: 0.98402995

01:01:00.920 --> 01:01:01.800
And yet in the area

NOTE Confidence: 0.98402995

01:01:01.800 --> 01:01:03.400
where the melanoma was extending

NOTE Confidence: 0.98402995

01:01:03.400 --> 01:01:05.000
farther superiorly, I was able

NOTE Confidence: 0.98402995

01:01:05.000 --> 01:01:06.359
to take a wider margin

NOTE Confidence: 0.98402995

01:01:06.359 --> 01:01:07.880
and capture the melanoma to

NOTE Confidence: 0.98402995

01:01:07.880 --> 01:01:08.940
achieve clear margins.

NOTE Confidence: 0.94495666

01:01:09.960 --> 01:01:10.920
And then we can actually

NOTE Confidence: 0.94495666

01:01:10.920 --> 01:01:12.494
do a local flap repair

NOTE Confidence: 0.94495666

01:01:12.494 --> 01:01:13.615
and and spare her a

NOTE Confidence: 0.94495666

01:01:13.615 --> 01:01:15.295
staged interpolation flap from the

NOTE Confidence: 0.94495666

01:01:15.295 --> 01:01:15.795
forehead.

NOTE Confidence: 0.9660581

01:01:16.255 --> 01:01:17.694
So so far, we've done

NOTE Confidence: 0.9660581

01:01:17.694 --> 01:01:19.055
a hundred and eighty cases,

NOTE Confidence: 0.9660581

01:01:19.295 --> 01:01:20.654
of melanoma with Mohs here

NOTE Confidence: 0.9660581

01:01:20.654 --> 01:01:21.775
at Yale, and this number

NOTE Confidence: 0.9660581

01:01:21.775 --> 01:01:22.994
continues to grow.

NOTE Confidence: 0.998121

01:01:24.015 --> 01:01:24.515
Okay.

NOTE Confidence: 0.9502154

01:01:25.150 --> 01:01:26.350
The data supports the use

NOTE Confidence: 0.9502154

01:01:26.350 --> 01:01:27.550
of Mohs surgery both for

NOTE Confidence: 0.9502154

01:01:27.550 --> 01:01:29.310
melanoma in situ and for

NOTE Confidence: 0.9502154

01:01:29.310 --> 01:01:30.290
invasive melanoma.

NOTE Confidence: 0.96467066

01:01:30.750 --> 01:01:31.870
So far, our data is

NOTE Confidence: 0.96467066

01:01:31.870 --> 01:01:33.390
only retrospective, so we don't

NOTE Confidence: 0.96467066

01:01:33.390 --> 01:01:34.750
have prospective data. But the

NOTE Confidence: 0.96467066

01:01:34.750 --> 01:01:36.430
retrospective data shows that there

NOTE Confidence: 0.96467066

01:01:36.430 --> 01:01:38.155
is a a clear benefit

NOTE Confidence: 0.96467066

01:01:38.155 --> 01:01:39.515
in terms of local recurrence

NOTE Confidence: 0.96467066

01:01:39.515 --> 01:01:40.494
with Mohs surgery,

NOTE Confidence: 0.997106

01:01:41.115 --> 01:01:42.494
being less than one percent

NOTE Confidence: 0.997106

01:01:42.635 --> 01:01:44.015
compared to standard excision,

NOTE Confidence: 0.99683917

01:01:44.315 --> 01:01:45.535
which is about eight percent.

NOTE Confidence: 0.9548942

01:01:45.994 --> 01:01:47.275
And if we do staged

NOTE Confidence: 0.9548942

01:01:47.275 --> 01:01:49.194
excision, not via Mohs with

NOTE Confidence: 0.9548942

01:01:49.194 --> 01:01:51.035
permanent suction processing, but with

NOTE Confidence: 0.9548942

01:01:51.035 --> 01:01:52.414
complete margin analysis,

NOTE Confidence: 0.9851867

01:01:52.750 --> 01:01:54.450
we can achieve a comparable

NOTE Confidence: 0.9851867

01:01:54.750 --> 01:01:56.190
low rate of local recurrence.

NOTE Confidence: 0.9851867

01:01:56.190 --> 01:01:57.790
So, again, it's not magic

NOTE Confidence: 0.9851867

01:01:57.790 --> 01:01:58.690
of Mohs surgery.

NOTE Confidence: 0.99731755

01:01:59.070 --> 01:02:00.030
It's the way that we

NOTE Confidence: 0.99731755

01:02:00.030 --> 01:02:01.890
examine the pathologic margin.

NOTE Confidence: 0.9693402

01:02:02.350 --> 01:02:03.410
And so we hypothesize

NOTE Confidence: 0.99664694

01:02:03.790 --> 01:02:05.550
that excision with complete margin

NOTE Confidence: 0.99664694

01:02:05.550 --> 01:02:07.550
analysis may allow for both

NOTE Confidence: 0.99664694

01:02:07.550 --> 01:02:08.210
more accurate

NOTE Confidence: 0.95988506

01:02:08.565 --> 01:02:10.265
and more complete tumor removal

NOTE Confidence: 0.95988506

01:02:10.484 --> 01:02:12.484
with narrower surgical margins and

NOTE Confidence: 0.95988506

01:02:12.484 --> 01:02:14.345
thereby decreased surgical morbidity.

NOTE Confidence: 0.97548366

01:02:16.005 --> 01:02:17.204
Okay. So we're gonna go

NOTE Confidence: 0.97548366

01:02:17.204 --> 01:02:18.565
back to our general principle

NOTE Confidence: 0.97548366

01:02:18.565 --> 01:02:20.565
here, of accurately staging a

NOTE Confidence: 0.97548366

01:02:20.565 --> 01:02:21.444
tumor, and this is why

NOTE Confidence: 0.97548366

01:02:21.444 --> 01:02:22.964
sentinel lymph node biopsy is

NOTE Confidence: 0.97548366

01:02:22.964 --> 01:02:23.625
so critical.

NOTE Confidence: 0.99117464

01:02:24.119 --> 01:02:25.500
It gives us that information

NOTE Confidence: 0.99117464

01:02:25.799 --> 01:02:26.539
on micronodal

NOTE Confidence: 0.91058725

01:02:27.079 --> 01:02:27.579
metastases,

NOTE Confidence: 0.9994429

01:02:27.960 --> 01:02:29.880
which will influence adjuvant treatment

NOTE Confidence: 0.9994429

01:02:29.880 --> 01:02:30.380
decisions.

NOTE Confidence: 0.9996816

01:02:31.079 --> 01:02:31.579
However,

NOTE Confidence: 0.91676074

01:02:32.119 --> 01:02:34.140
GEPs now offer potentially

NOTE Confidence: 0.99204767

01:02:34.519 --> 01:02:36.200
another way to access the

NOTE Confidence: 0.99204767

01:02:36.200 --> 01:02:37.019
same question.

NOTE Confidence: 0.9742643

01:02:37.935 --> 01:02:39.635
So this is the CPGEP,

NOTE Confidence: 0.9650429

01:02:40.095 --> 01:02:42.015
the clinical pathologic gene expression

NOTE Confidence: 0.9650429

01:02:42.015 --> 01:02:42.515
profiling

NOTE Confidence: 0.8226156

01:02:42.975 --> 01:02:43.775
Merlin test.

NOTE Confidence: 0.87705153

01:02:44.415 --> 01:02:46.115
This is a large prospective

NOTE Confidence: 0.9093314

01:02:46.575 --> 01:02:47.075
multicenter

NOTE Confidence: 0.9401287

01:02:47.375 --> 01:02:48.435
blinded evaluation,

NOTE Confidence: 0.94618076

01:02:48.895 --> 01:02:50.675
that doctor Alino already presented.

NOTE Confidence: 0.94618076

01:02:50.895 --> 01:02:52.175
Just wanna highlight a couple

NOTE Confidence: 0.94618076

01:02:52.175 --> 01:02:53.155
features here.

NOTE Confidence: 0.9914078

01:02:53.680 --> 01:02:55.040
When I say blinded, it

NOTE Confidence: 0.9914078

01:02:55.040 --> 01:02:56.480
means that the surgeons doing

NOTE Confidence: 0.9914078

01:02:56.480 --> 01:02:58.100
the sentinel lymph node procedure

NOTE Confidence: 0.9914078

01:02:58.320 --> 01:02:59.700
did not know the patient's

NOTE Confidence: 0.9914078

01:02:59.840 --> 01:03:01.520
GEP results, so they were

NOTE Confidence: 0.9914078

01:03:01.520 --> 01:03:02.580
blinded to that.

NOTE Confidence: 0.96409935

01:03:03.680 --> 01:03:04.800
And, also, just to highlight

NOTE Confidence: 0.96409935

01:03:04.800 --> 01:03:06.720
that this GEP includes both

NOTE Confidence: 0.96409935

01:03:06.720 --> 01:03:08.240
the gene expression as well

NOTE Confidence: 0.96409935

01:03:08.240 --> 01:03:09.315
as the patient's age and

NOTE Confidence: 0.96409935

01:03:09.315 --> 01:03:10.375
Breslow death.

NOTE Confidence: 0.98658705

01:03:10.755 --> 01:03:11.555
And that's part of the

NOTE Confidence: 0.98658705

01:03:11.555 --> 01:03:13.075
reason why for these t

NOTE Confidence: 0.98658705

01:03:13.075 --> 01:03:13.895
three tumors,

NOTE Confidence: 0.9878288

01:03:14.515 --> 01:03:16.195
a very small fraction of

NOTE Confidence: 0.9878288

01:03:16.195 --> 01:03:17.875
them are actually classified as

NOTE Confidence: 0.9878288

01:03:17.875 --> 01:03:18.615
low risk,

NOTE Confidence: 0.9069252

01:03:19.474 --> 01:03:20.595
both because they have an

NOTE Confidence: 0.9069252

01:03:20.595 --> 01:03:21.095
increased,

NOTE Confidence: 0.97755086

01:03:21.670 --> 01:03:23.030
sort of aggressiveness of their

NOTE Confidence: 0.97755086

01:03:23.030 --> 01:03:24.570
gene expression, but also because

NOTE Confidence: 0.9698271

01:03:25.030 --> 01:03:26.790
this test includes the Breslow

NOTE Confidence: 0.9698271

01:03:26.790 --> 01:03:28.150
depth. So it's actually pretty

NOTE Confidence: 0.9698271

01:03:28.150 --> 01:03:29.270
rare to get a low

NOTE Confidence: 0.9698271

01:03:29.270 --> 01:03:30.090
risk result,

NOTE Confidence: 0.9840414

01:03:30.550 --> 01:03:31.590
with these t three tumors,

NOTE Confidence: 0.9840414

01:03:31.590 --> 01:03:32.390
and we can see that

NOTE Confidence: 0.9840414

01:03:32.390 --> 01:03:34.170
it doesn't very accurately predict,

NOTE Confidence: 0.97749233

01:03:34.550 --> 01:03:36.070
sentinel lymph node status in

NOTE Confidence: 0.97749233

01:03:36.070 --> 01:03:37.395
these groups of patients.

NOTE Confidence: 0.980537

01:03:37.695 --> 01:03:38.655
However, if we go to

NOTE Confidence: 0.980537

01:03:38.655 --> 01:03:40.335
this stage, the stage one

NOTE Confidence: 0.980537

01:03:40.335 --> 01:03:41.615
b subgroup, which is t

NOTE Confidence: 0.980537

01:03:41.615 --> 01:03:42.575
one b and t two

NOTE Confidence: 0.980537

01:03:42.575 --> 01:03:43.695
a, and you'll note that

NOTE Confidence: 0.980537

01:03:43.695 --> 01:03:44.995
this is actually the largest

NOTE Confidence: 0.980537

01:03:45.055 --> 01:03:46.495
fraction of patients in this

NOTE Confidence: 0.980537

01:03:46.495 --> 01:03:46.995
study.

NOTE Confidence: 0.99361676

01:03:48.015 --> 01:03:49.375
About half of these patients

NOTE Confidence: 0.99361676

01:03:49.375 --> 01:03:51.180
overall were were classified as

NOTE Confidence: 0.99361676

01:03:51.180 --> 01:03:52.780
GEP low risk, and we

NOTE Confidence: 0.99361676

01:03:52.780 --> 01:03:54.140
see that it really did

NOTE Confidence: 0.99361676

01:03:54.140 --> 01:03:55.580
impact the rate of sentinel

NOTE Confidence: 0.99361676

01:03:55.580 --> 01:03:56.560
lymph node positivity.

NOTE Confidence: 0.9794392

01:03:56.940 --> 01:03:57.820
So in the t one

NOTE Confidence: 0.9794392

01:03:57.820 --> 01:03:59.020
b's, if they were low

NOTE Confidence: 0.9794392

01:03:59.020 --> 01:04:00.060
risk, they were only five

NOTE Confidence: 0.9794392

01:04:00.060 --> 01:04:02.160
percent, sentinel lymph node positive

NOTE Confidence: 0.9794392

01:04:02.380 --> 01:04:03.900
compared to sixteen percent in

NOTE Confidence: 0.9794392

01:04:03.900 --> 01:04:04.720
the high risk,

NOTE Confidence: 0.9802465

01:04:05.505 --> 01:04:06.964
similar for t two a.

NOTE Confidence: 0.9802465

01:04:07.025 --> 01:04:08.224
So it's the stage one

NOTE Confidence: 0.9802465

01:04:08.224 --> 01:04:09.825
b subgroup where this test

NOTE Confidence: 0.9802465

01:04:09.825 --> 01:04:11.045
can be most useful.

NOTE Confidence: 0.99950993

01:04:11.345 --> 01:04:12.484
And this is asking

NOTE Confidence: 0.9586586

01:04:12.785 --> 01:04:14.785
only the specific question of

NOTE Confidence: 0.9586586

01:04:14.785 --> 01:04:16.545
can we predict sentinel lymph

NOTE Confidence: 0.9586586

01:04:16.545 --> 01:04:18.704
node status and thereby perhaps

NOTE Confidence: 0.9586586

01:04:18.704 --> 01:04:20.065
avoid sentinel lymph node in

NOTE Confidence: 0.9586586

01:04:20.065 --> 01:04:20.885
certain patients.

NOTE Confidence: 0.9923299

01:04:21.960 --> 01:04:23.080
So then that brings us

NOTE Confidence: 0.9923299

01:04:23.080 --> 01:04:24.060
to the trial.

NOTE Confidence: 0.9711472

01:04:24.360 --> 01:04:25.660
So this is the ICEMAN

NOTE Confidence: 0.9711472

01:04:25.720 --> 01:04:27.720
trial intelligent choice of excision

NOTE Confidence: 0.9711472

01:04:27.720 --> 01:04:29.740
margin. And the primary objective

NOTE Confidence: 0.9711472

01:04:29.880 --> 01:04:31.640
is to compare three year

NOTE Confidence: 0.9711472

01:04:31.640 --> 01:04:33.640
recurrence free survival in patients

NOTE Confidence: 0.9711472

01:04:33.640 --> 01:04:34.920
that are treated with narrow

NOTE Confidence: 0.9711472

01:04:34.920 --> 01:04:36.619
excision versus wide excision.

NOTE Confidence: 0.98146

01:04:37.205 --> 01:04:39.285
The secondary objective is to,

NOTE Confidence: 0.97071254

01:04:40.005 --> 01:04:42.165
assess disease free survival, especially

NOTE Confidence: 0.97071254

01:04:42.165 --> 01:04:43.705
looking at nodal disease

NOTE Confidence: 0.9583455

01:04:44.645 --> 01:04:46.085
in patients who were treated

NOTE Confidence: 0.9583455

01:04:46.085 --> 01:04:47.685
with nodal surveillance without a

NOTE Confidence: 0.9583455

01:04:47.685 --> 01:04:49.065
sentinel lymph node biopsy.

NOTE Confidence: 0.92589384

01:04:49.460 --> 01:04:50.339
So here's a setup of

NOTE Confidence: 0.92589384

01:04:50.339 --> 01:04:51.940
the trial. Patients with clinical

NOTE Confidence: 0.92589384

01:04:51.940 --> 01:04:53.240
stage one invasive melanoma

NOTE Confidence: 0.97489846

01:04:53.779 --> 01:04:55.400
that are classified as Merlin

NOTE Confidence: 0.97489846

01:04:55.460 --> 01:04:57.400
low risk. So all patients,

NOTE Confidence: 0.9700181

01:04:58.099 --> 01:04:59.539
are tested with the GEP,

NOTE Confidence: 0.9700181

01:04:59.539 --> 01:05:00.500
and only those that are

NOTE Confidence: 0.9700181

01:05:00.500 --> 01:05:02.019
low risk are enrolled in

NOTE Confidence: 0.9700181

01:05:02.019 --> 01:05:03.859
this study. They're randomized to

NOTE Confidence: 0.9700181

01:05:03.859 --> 01:05:05.325
either narrow excision or wide

NOTE Confidence: 0.9700181

01:05:05.325 --> 01:05:06.525
excision. And we can see

NOTE Confidence: 0.9700181

01:05:06.525 --> 01:05:07.885
what that actually means. Narrow

NOTE Confidence: 0.9700181

01:05:07.885 --> 01:05:09.405
excision is zero point five

NOTE Confidence: 0.9700181

01:05:09.405 --> 01:05:09.905
centimeters

NOTE Confidence: 0.9717204

01:05:10.445 --> 01:05:12.285
with complete margin analysis for

NOTE Confidence: 0.9717204

01:05:12.285 --> 01:05:13.805
high risk locations or high

NOTE Confidence: 0.9717204

01:05:13.805 --> 01:05:14.545
risk pathology.

NOTE Confidence: 0.9704975

01:05:15.005 --> 01:05:16.125
And then the wide excision

NOTE Confidence: 0.9704975

01:05:16.125 --> 01:05:17.905
is standard treatment per NCCN

NOTE Confidence: 0.9704975

01:05:18.045 --> 01:05:18.545
guidelines.

NOTE Confidence: 0.999625

01:05:19.820 --> 01:05:20.960
And none of these patients

NOTE Confidence: 0.97972035

01:05:21.260 --> 01:05:22.780
will have a sentinel lymph

NOTE Confidence: 0.97972035

01:05:22.780 --> 01:05:24.140
node biopsy as part of

NOTE Confidence: 0.97972035

01:05:24.140 --> 01:05:24.800
the trial.

NOTE Confidence: 0.9620287

01:05:25.580 --> 01:05:26.780
And these are the inclusion

NOTE Confidence: 0.9620287

01:05:26.780 --> 01:05:27.280
criteria,

NOTE Confidence: 0.96857005

01:05:27.820 --> 01:05:29.260
only t one b, t

NOTE Confidence: 0.96857005

01:05:29.260 --> 01:05:30.000
two a,

NOTE Confidence: 0.9968009

01:05:30.460 --> 01:05:30.960
or

NOTE Confidence: 0.9921977

01:05:31.260 --> 01:05:32.565
t one a with depth

NOTE Confidence: 0.9921977

01:05:32.645 --> 01:05:33.845
depth greater than zero point

NOTE Confidence: 0.9921977

01:05:33.845 --> 01:05:35.365
five and greater than one

NOTE Confidence: 0.9921977

01:05:35.365 --> 01:05:37.204
high risk feature, which includes

NOTE Confidence: 0.9921977

01:05:37.204 --> 01:05:37.704
lymphovascular

NOTE Confidence: 0.92465657

01:05:38.085 --> 01:05:39.305
invasion or mitoses.

NOTE Confidence: 0.9925767

01:05:40.165 --> 01:05:41.045
And they all have to

NOTE Confidence: 0.9925767

01:05:41.045 --> 01:05:42.905
be GEP low risk.

NOTE Confidence: 0.97411245

01:05:44.085 --> 01:05:45.285
In case you need to

NOTE Confidence: 0.97411245

01:05:45.285 --> 01:05:46.885
remind yourself what these categories

NOTE Confidence: 0.97411245

01:05:46.885 --> 01:05:47.845
are, these are the actual

NOTE Confidence: 0.97411245

01:05:47.845 --> 01:05:48.540
preslow deaths.

NOTE Confidence: 0.99710554

01:05:49.420 --> 01:05:50.460
And so I mentioned that

NOTE Confidence: 0.99710554

01:05:50.460 --> 01:05:51.660
sentinel lymph node biopsy is

NOTE Confidence: 0.99710554

01:05:51.660 --> 01:05:52.540
not part of the trial,

NOTE Confidence: 0.99710554

01:05:52.540 --> 01:05:53.820
but it may be performed

NOTE Confidence: 0.99710554

01:05:53.820 --> 01:05:55.180
at physician discretion, which is

NOTE Confidence: 0.99710554

01:05:55.180 --> 01:05:55.680
important.

NOTE Confidence: 0.96926695

01:05:55.980 --> 01:05:57.020
So if we feel that

NOTE Confidence: 0.96926695

01:05:57.020 --> 01:05:58.540
a patient really would benefit

NOTE Confidence: 0.96926695

01:05:58.540 --> 01:05:59.980
from having sentinel lymph node

NOTE Confidence: 0.96926695

01:05:59.980 --> 01:06:01.660
biopsy even with a GEP

NOTE Confidence: 0.96926695

01:06:01.660 --> 01:06:02.815
low risk score, then then

NOTE Confidence: 0.96926695

01:06:02.815 --> 01:06:03.695
we can still do that

NOTE Confidence: 0.96926695

01:06:03.695 --> 01:06:04.835
as part of this trial.

NOTE Confidence: 0.95065284

01:06:06.255 --> 01:06:07.135
This is a large study

NOTE Confidence: 0.95065284

01:06:07.135 --> 01:06:08.335
with the planned enrollment of

NOTE Confidence: 0.95065284

01:06:08.335 --> 01:06:09.775
a thousand patients at multiple

NOTE Confidence: 0.95065284

01:06:09.775 --> 01:06:11.375
sites. It is currently already

NOTE Confidence: 0.95065284

01:06:11.375 --> 01:06:12.655
enrolling in a few sites,

NOTE Confidence: 0.95065284

01:06:12.655 --> 01:06:13.855
and, hopefully, Yale will be

NOTE Confidence: 0.95065284

01:06:13.855 --> 01:06:14.915
coming on soon.

NOTE Confidence: 0.9878371

01:06:16.100 --> 01:06:17.700
For these early stage melanoma,

NOTE Confidence: 0.9878371

01:06:17.700 --> 01:06:19.220
we expect a very good

NOTE Confidence: 0.9878371

01:06:19.220 --> 01:06:20.740
recurrence free survival of ninety

NOTE Confidence: 0.9878371

01:06:20.740 --> 01:06:21.860
eight percent at three years.

NOTE Confidence: 0.9878371

01:06:21.860 --> 01:06:22.500
So we really have to

NOTE Confidence: 0.9878371

01:06:22.500 --> 01:06:23.380
have a large study to

NOTE Confidence: 0.9878371

01:06:23.380 --> 01:06:24.740
be able to detect any

NOTE Confidence: 0.9878371

01:06:24.740 --> 01:06:26.580
potential difference here, and this

NOTE Confidence: 0.9878371

01:06:26.580 --> 01:06:27.400
is a noninferiority

NOTE Confidence: 0.99720025

01:06:27.940 --> 01:06:28.440
design.

NOTE Confidence: 0.999253

01:06:29.065 --> 01:06:30.105
And we're also looking at

NOTE Confidence: 0.999253

01:06:30.105 --> 01:06:31.965
secondary outcomes of surgical morbidity

NOTE Confidence: 0.9915957

01:06:32.425 --> 01:06:33.865
and quality of life measures,

NOTE Confidence: 0.9915957

01:06:33.865 --> 01:06:34.925
which we expect,

NOTE Confidence: 0.99263054

01:06:35.385 --> 01:06:36.905
will be less in patients

NOTE Confidence: 0.99263054

01:06:36.905 --> 01:06:38.265
that are randomized to narrow

NOTE Confidence: 0.99263054

01:06:38.265 --> 01:06:38.765
excision.

NOTE Confidence: 0.9946516

01:06:40.105 --> 01:06:41.325
So just to summarize,

NOTE Confidence: 0.9989895

01:06:42.380 --> 01:06:43.820
know, we're thinking about our

NOTE Confidence: 0.9989895

01:06:43.820 --> 01:06:45.280
goals of surgical management,

NOTE Confidence: 0.9933135

01:06:45.740 --> 01:06:47.520
including both staging the tumor

NOTE Confidence: 0.9933135

01:06:47.580 --> 01:06:49.440
and optimizing local control.

NOTE Confidence: 0.9906512

01:06:50.300 --> 01:06:52.140
Complete margin analysis may allow

NOTE Confidence: 0.9906512

01:06:52.140 --> 01:06:53.580
us to have less morbid

NOTE Confidence: 0.9906512

01:06:53.580 --> 01:06:55.280
and yet still complete surgical

NOTE Confidence: 0.9906512

01:06:55.340 --> 01:06:56.860
resection with a narrow initial

NOTE Confidence: 0.9906512

01:06:56.860 --> 01:06:57.360
margin.

NOTE Confidence: 0.9663021

01:06:57.935 --> 01:06:59.395
And then using a GEP

NOTE Confidence: 0.98341626

01:06:59.695 --> 01:07:00.895
can maybe help us do

NOTE Confidence: 0.98341626

01:07:00.895 --> 01:07:02.175
some of the staging without

NOTE Confidence: 0.98341626

01:07:02.175 --> 01:07:03.555
a sentinel lymph node biopsy,

NOTE Confidence: 0.9932467

01:07:04.095 --> 01:07:05.635
in select groups of patients,

NOTE Confidence: 0.9932467

01:07:05.695 --> 01:07:07.215
especially t one b, t

NOTE Confidence: 0.9932467

01:07:07.215 --> 01:07:08.115
two a melanomas,

NOTE Confidence: 0.93980443

01:07:08.975 --> 01:07:10.575
that come back as as

NOTE Confidence: 0.93980443

01:07:10.575 --> 01:07:12.095
low risk on their GEP

NOTE Confidence: 0.93980443

01:07:12.095 --> 01:07:12.595
testing.

NOTE Confidence: 0.9998526

01:07:13.440 --> 01:07:15.460
So I will stop there.

NOTE Confidence: 0.9998526

01:07:15.520 --> 01:07:16.260
Thank you.

NOTE Confidence: 0.9419149

01:07:22.640 --> 01:07:24.079
Thank you so much, doctor

NOTE Confidence: 0.9419149

01:07:24.079 --> 01:07:25.140
Christiansen, sir.

NOTE Confidence: 0.9748419

01:07:25.845 --> 01:07:27.605
It's nice everyone has already

NOTE Confidence: 0.9748419

01:07:27.605 --> 01:07:29.224
kind of laid out the

NOTE Confidence: 0.9793103

01:07:29.525 --> 01:07:30.025
groundwork,

NOTE Confidence: 0.9867742

01:07:30.724 --> 01:07:32.585
about all these very fancy

NOTE Confidence: 0.9867742

01:07:32.724 --> 01:07:35.045
gene expression profiling assays. And

NOTE Confidence: 0.9867742

01:07:35.045 --> 01:07:36.165
so my job now is

NOTE Confidence: 0.9867742

01:07:36.165 --> 01:07:37.065
trying to

NOTE Confidence: 0.98379064

01:07:37.365 --> 01:07:38.645
take all of this new

NOTE Confidence: 0.98379064

01:07:38.645 --> 01:07:40.085
technology and how do we

NOTE Confidence: 0.98379064

01:07:40.085 --> 01:07:41.790
integrate it best into clinical

NOTE Confidence: 0.98379064

01:07:42.030 --> 01:07:43.250
practice to really

NOTE Confidence: 0.9506708

01:07:43.550 --> 01:07:44.590
move the needle in terms

NOTE Confidence: 0.9506708

01:07:44.590 --> 01:07:46.270
of improving patient outcomes while

NOTE Confidence: 0.9506708

01:07:46.270 --> 01:07:48.210
minimizing morbidity and overtreatment.

NOTE Confidence: 0.9821655

01:07:48.910 --> 01:07:49.550
And so one of the

NOTE Confidence: 0.9821655

01:07:49.550 --> 01:07:50.990
things that I'll talk briefly

NOTE Confidence: 0.9821655

01:07:50.990 --> 01:07:51.870
about is kind of the

NOTE Confidence: 0.9821655

01:07:51.870 --> 01:07:53.230
difference between how we use

NOTE Confidence: 0.9821655

01:07:53.230 --> 01:07:54.990
these assays in melanoma versus

NOTE Confidence: 0.9821655

01:07:54.990 --> 01:07:56.930
in cutaneous squamous cell carcinomas.

NOTE Confidence: 0.9626394

01:07:57.545 --> 01:07:58.825
And really there are three

NOTE Confidence: 0.9626394

01:07:58.825 --> 01:08:00.905
main goals of trying to

NOTE Confidence: 0.9626394

01:08:00.905 --> 01:08:03.305
utilize GEPs in clinical decision

NOTE Confidence: 0.9626394

01:08:03.305 --> 01:08:04.825
making. One is, you know,

NOTE Confidence: 0.9626394

01:08:04.825 --> 01:08:06.345
the question is, can we

NOTE Confidence: 0.9626394

01:08:06.345 --> 01:08:08.045
avoid central lymph node biopsies

NOTE Confidence: 0.9626394

01:08:08.265 --> 01:08:09.625
in individuals who are at

NOTE Confidence: 0.9626394

01:08:09.625 --> 01:08:11.350
low risk, and reduce the

NOTE Confidence: 0.9626394

01:08:11.350 --> 01:08:13.290
morbidity of surgical resection?

NOTE Confidence: 0.986006

01:08:13.750 --> 01:08:14.710
You know, how does that

NOTE Confidence: 0.986006

01:08:14.710 --> 01:08:16.070
score really inform whether or

NOTE Confidence: 0.986006

01:08:16.070 --> 01:08:17.610
not the patient needs adjuvant

NOTE Confidence: 0.986006

01:08:17.750 --> 01:08:19.370
therapy to try to minimize

NOTE Confidence: 0.986006

01:08:19.430 --> 01:08:20.489
the stomach toxicities

NOTE Confidence: 0.9941591

01:08:20.790 --> 01:08:21.989
for people who don't need

NOTE Confidence: 0.9941591

01:08:21.989 --> 01:08:23.590
additional treatment and will have

NOTE Confidence: 0.9941591

01:08:23.590 --> 01:08:24.890
a good outcome regardless?

NOTE Confidence: 0.9989565

01:08:25.590 --> 01:08:27.104
And then how do we

NOTE Confidence: 0.9991825

01:08:27.405 --> 01:08:29.025
utilize this information

NOTE Confidence: 0.98820996

01:08:29.325 --> 01:08:30.145
about risk

NOTE Confidence: 0.96376896

01:08:30.445 --> 01:08:32.385
to guide surveillance? Do individuals

NOTE Confidence: 0.96376896

01:08:32.525 --> 01:08:33.985
who have high risk tumors

NOTE Confidence: 0.96376896

01:08:34.125 --> 01:08:35.265
need more surveillance,

NOTE Confidence: 0.9773393

01:08:35.725 --> 01:08:37.905
more frequent visits, more frequent

NOTE Confidence: 0.9773393

01:08:38.125 --> 01:08:39.965
examinations and scans as opposed

NOTE Confidence: 0.9773393

01:08:39.965 --> 01:08:41.165
to those with low risk

NOTE Confidence: 0.9773393

01:08:41.165 --> 01:08:41.665
disease?

NOTE Confidence: 0.9339176

01:08:43.380 --> 01:08:44.740
So this is just kind

NOTE Confidence: 0.9339176

01:08:44.740 --> 01:08:46.340
of comparing again the MERLIN

NOTE Confidence: 0.9339176

01:08:46.340 --> 01:08:48.600
and the CASEL bioscience testing.

NOTE Confidence: 0.9861778

01:08:49.060 --> 01:08:50.340
I really only focused on

NOTE Confidence: 0.9861778

01:08:50.340 --> 01:08:51.780
the assays that are available

NOTE Confidence: 0.9861778

01:08:51.780 --> 01:08:53.240
here in the United States.

NOTE Confidence: 0.95319426

01:08:54.260 --> 01:08:55.755
But really, as, you know,

NOTE Confidence: 0.95319426

01:08:55.755 --> 01:08:57.614
my colleagues have already discussed,

NOTE Confidence: 0.8738388

01:08:58.314 --> 01:09:00.635
Merlin has two categories, high

NOTE Confidence: 0.8738388

01:09:00.635 --> 01:09:02.655
versus low, whereas Cassell has

NOTE Confidence: 0.945929

01:09:02.955 --> 01:09:05.215
four different categories, 1A, 1B,

NOTE Confidence: 0.945929

01:09:05.275 --> 01:09:07.215
2A, 2Bs in melanoma.

NOTE Confidence: 0.9636985

01:09:08.715 --> 01:09:10.235
Really the Merlin is kind

NOTE Confidence: 0.9636985

01:09:10.235 --> 01:09:12.450
of geared towards looking at

NOTE Confidence: 0.9636985

01:09:12.450 --> 01:09:14.310
predicting sentinel lymph node positivity

NOTE Confidence: 0.9636985

01:09:14.610 --> 01:09:16.050
to guide decision making and

NOTE Confidence: 0.9636985

01:09:16.050 --> 01:09:17.189
lower risk melanomas,

NOTE Confidence: 0.9647566

01:09:17.650 --> 01:09:19.729
whereas CASEL really tries to

NOTE Confidence: 0.9647566

01:09:19.729 --> 01:09:21.590
address the question about recurrence

NOTE Confidence: 0.9647566

01:09:21.810 --> 01:09:22.950
risk and prognostication.

NOTE Confidence: 0.92500854

01:09:26.745 --> 01:09:28.745
The real question is these

NOTE Confidence: 0.92500854

01:09:28.745 --> 01:09:30.125
tests are very expensive.

NOTE Confidence: 0.99556124

01:09:30.425 --> 01:09:30.925
They're

NOTE Confidence: 0.9321167

01:09:31.305 --> 01:09:32.905
time consuming. There's a lag

NOTE Confidence: 0.9321167

01:09:32.905 --> 01:09:34.185
time in before you get

NOTE Confidence: 0.9321167

01:09:34.185 --> 01:09:34.925
the results.

NOTE Confidence: 0.99701923

01:09:35.465 --> 01:09:37.165
And given the cost,

NOTE Confidence: 0.9991805

01:09:38.025 --> 01:09:39.945
does this information really add

NOTE Confidence: 0.9991805

01:09:39.945 --> 01:09:41.645
overall value to the care?

NOTE Confidence: 0.94637066

01:09:41.970 --> 01:09:43.010
You know, we talk about

NOTE Confidence: 0.94637066

01:09:43.010 --> 01:09:44.070
nomograms and,

NOTE Confidence: 0.95487815

01:09:45.650 --> 01:09:46.770
in determining whether or not

NOTE Confidence: 0.95487815

01:09:46.770 --> 01:09:47.810
patients have a high risk

NOTE Confidence: 0.95487815

01:09:47.810 --> 01:09:49.010
of the sentinel lymph node

NOTE Confidence: 0.95487815

01:09:49.010 --> 01:09:51.110
positivity to determine lymph node

NOTE Confidence: 0.95487815

01:09:51.250 --> 01:09:51.750
biopsies.

NOTE Confidence: 0.99532795

01:09:52.930 --> 01:09:54.290
We have very good long

NOTE Confidence: 0.99532795

01:09:54.290 --> 01:09:54.790
term

NOTE Confidence: 0.9411258

01:09:55.665 --> 01:09:56.165
AJCC

NOTE Confidence: 0.9831516

01:09:57.104 --> 01:09:58.804
melanoma specific recurrence,

NOTE Confidence: 0.9393283

01:10:00.224 --> 01:10:01.364
specific survival,

NOTE Confidence: 0.9885684

01:10:01.824 --> 01:10:03.284
and all of these latter,

NOTE Confidence: 0.9395237

01:10:04.625 --> 01:10:06.304
you know, statistics are free.

NOTE Confidence: 0.9395237

01:10:06.304 --> 01:10:07.744
So, what exactly is the

NOTE Confidence: 0.9395237

01:10:07.744 --> 01:10:09.204
GEP testing contributing?

NOTE Confidence: 0.9188053

01:10:10.410 --> 01:10:12.010
In addition to this, you

NOTE Confidence: 0.9188053

01:10:12.010 --> 01:10:13.770
know, we obviously from the

NOTE Confidence: 0.9188053

01:10:13.770 --> 01:10:15.050
pros and cons about the

NOTE Confidence: 0.9188053

01:10:15.050 --> 01:10:16.410
discussion and how these assays

NOTE Confidence: 0.9188053

01:10:16.410 --> 01:10:17.850
were designed and whether geared

NOTE Confidence: 0.9188053

01:10:17.850 --> 01:10:18.670
towards addressing,

NOTE Confidence: 0.9841813

01:10:19.130 --> 01:10:20.590
there are obvious flaws.

NOTE Confidence: 0.9872021

01:10:21.050 --> 01:10:22.570
They're not perfect. No single

NOTE Confidence: 0.9872021

01:10:22.570 --> 01:10:24.410
assay is going to yield

NOTE Confidence: 0.9872021

01:10:24.410 --> 01:10:24.990
the exact

NOTE Confidence: 0.9554922

01:10:25.575 --> 01:10:27.255
data that is required. And

NOTE Confidence: 0.9554922

01:10:27.255 --> 01:10:27.995
there's always

NOTE Confidence: 0.99968576

01:10:28.535 --> 01:10:29.435
some stage

NOTE Confidence: 0.93723756

01:10:29.735 --> 01:10:32.235
or some factor clinical pathologically,

NOTE Confidence: 0.99812

01:10:33.495 --> 01:10:34.854
that may not be well

NOTE Confidence: 0.99812

01:10:34.854 --> 01:10:36.315
represented in the assay.

NOTE Confidence: 0.85308725

01:10:36.695 --> 01:10:38.295
So for example, this is

NOTE Confidence: 0.85308725

01:10:38.295 --> 01:10:39.815
the Castle Bio and Science

NOTE Confidence: 0.85308725

01:10:39.815 --> 01:10:40.315
testing,

NOTE Confidence: 0.998897

01:10:40.680 --> 01:10:42.360
looking at the estimated proportion

NOTE Confidence: 0.998897

01:10:42.360 --> 01:10:43.660
of patients with melanoma

NOTE Confidence: 0.9270368

01:10:44.520 --> 01:10:46.199
who are correctly classified as

NOTE Confidence: 0.9270368

01:10:46.199 --> 01:10:47.239
high risk. And you can

NOTE Confidence: 0.9270368

01:10:47.239 --> 01:10:48.460
see the stage ones,

NOTE Confidence: 0.96623254

01:10:49.479 --> 01:10:50.280
did worse,

NOTE Confidence: 0.99216753

01:10:50.600 --> 01:10:52.695
in this setting. Whereas if

NOTE Confidence: 0.99216753

01:10:52.695 --> 01:10:53.735
you kind of flip this

NOTE Confidence: 0.99216753

01:10:53.735 --> 01:10:55.095
and look at the estimated

NOTE Confidence: 0.99216753

01:10:55.095 --> 01:10:56.955
proportion of patients without melanoma

NOTE Confidence: 0.99216753

01:10:57.095 --> 01:10:58.955
recurrence that were correctly classified

NOTE Confidence: 0.99216753

01:10:59.015 --> 01:10:59.915
as low risk,

NOTE Confidence: 0.94107145

01:11:00.615 --> 01:11:02.055
again, the stage twos in

NOTE Confidence: 0.94107145

01:11:02.055 --> 01:11:03.275
this situation

NOTE Confidence: 0.99545205

01:11:03.814 --> 01:11:05.015
did a little bit worse

NOTE Confidence: 0.99545205

01:11:05.015 --> 01:11:06.155
based on the assay.

NOTE Confidence: 0.94762105

01:11:06.890 --> 01:11:08.650
So I think in general,

NOTE Confidence: 0.94762105

01:11:08.650 --> 01:11:10.410
when you kinda summarize these

NOTE Confidence: 0.94762105

01:11:10.410 --> 01:11:12.590
different studies that led to,

NOTE Confidence: 0.9112563

01:11:13.370 --> 01:11:15.150
the evaluation of these

NOTE Confidence: 0.9484104

01:11:15.450 --> 01:11:17.790
clinical assays in in patients,

NOTE Confidence: 0.97549385

01:11:18.330 --> 01:11:20.330
really, the consensus is that

NOTE Confidence: 0.97549385

01:11:20.330 --> 01:11:22.035
maybe they're not quite ready

NOTE Confidence: 0.97549385

01:11:22.035 --> 01:11:23.814
yet for prime time usage.

NOTE Confidence: 0.83617157

01:11:25.395 --> 01:11:26.695
The Merlin has,

NOTE Confidence: 0.97028655

01:11:27.314 --> 01:11:28.614
a nod in the NCCN

NOTE Confidence: 0.97028655

01:11:28.835 --> 01:11:30.035
to consider it,

NOTE Confidence: 0.9035613

01:11:30.435 --> 01:11:32.354
but ultimately, it should not

NOTE Confidence: 0.9035613

01:11:32.354 --> 01:11:32.854
supersede,

NOTE Confidence: 0.99193156

01:11:34.090 --> 01:11:36.910
clinical pathological features, clinical staging,

NOTE Confidence: 0.99039066

01:11:37.690 --> 01:11:38.729
and really should be used

NOTE Confidence: 0.99039066

01:11:38.729 --> 01:11:40.090
in the context as an

NOTE Confidence: 0.99039066

01:11:40.090 --> 01:11:42.250
investigational tool because there's still

NOTE Confidence: 0.99039066

01:11:42.250 --> 01:11:43.770
so much that we still

NOTE Confidence: 0.99039066

01:11:43.770 --> 01:11:45.290
need to clarify in regards

NOTE Confidence: 0.99039066

01:11:45.290 --> 01:11:46.890
to how best to implement

NOTE Confidence: 0.99039066

01:11:46.890 --> 01:11:49.015
them, what they ultimately mean,

NOTE Confidence: 0.99039066

01:11:49.015 --> 01:11:50.795
what the long term survival,

NOTE Confidence: 0.99039066

01:11:50.854 --> 01:11:51.354
recurrence

NOTE Confidence: 0.9115127

01:11:52.535 --> 01:11:54.535
risk factors, and overall survival

NOTE Confidence: 0.9115127

01:11:54.535 --> 01:11:55.755
is for these individuals.

NOTE Confidence: 0.9063572

01:11:56.375 --> 01:11:57.575
So really right now, they're

NOTE Confidence: 0.9063572

01:11:57.575 --> 01:11:59.495
still geared towards the, as

NOTE Confidence: 0.9063572

01:11:59.495 --> 01:12:00.235
an investigational

NOTE Confidence: 0.99967015

01:12:00.535 --> 01:12:01.035
tool

NOTE Confidence: 0.9775794

01:12:01.500 --> 01:12:02.960
as part of clinical trials

NOTE Confidence: 0.9775794

01:12:03.099 --> 01:12:04.559
and in the research setting.

NOTE Confidence: 0.9577004

01:12:05.900 --> 01:12:06.939
This is kind of the

NOTE Confidence: 0.9577004

01:12:06.939 --> 01:12:09.739
melanoma specific survival breakdown by

NOTE Confidence: 0.9577004

01:12:09.739 --> 01:12:10.239
stage

NOTE Confidence: 0.9010483

01:12:10.860 --> 01:12:12.219
at five years and ten

NOTE Confidence: 0.9010483

01:12:12.219 --> 01:12:13.900
years. And as you can

NOTE Confidence: 0.9010483

01:12:13.900 --> 01:12:15.420
see, really, we try to

NOTE Confidence: 0.9010483

01:12:15.420 --> 01:12:17.915
gear therapy, any additional adjuvant

NOTE Confidence: 0.9010483

01:12:17.975 --> 01:12:19.275
therapy post surgery

NOTE Confidence: 0.93987674

01:12:19.735 --> 01:12:21.335
in those individuals that have

NOTE Confidence: 0.93987674

01:12:21.335 --> 01:12:22.314
a higher risk

NOTE Confidence: 0.89507055

01:12:22.695 --> 01:12:25.755
of, morbidity, mortality for melanoma.

NOTE Confidence: 0.8572183

01:12:26.295 --> 01:12:27.415
And so really it's those

NOTE Confidence: 0.8572183

01:12:27.415 --> 01:12:29.335
stage IIBs and beyond even

NOTE Confidence: 0.8572183

01:12:29.335 --> 01:12:30.660
including oligometastatic stage four

NOTE Confidence: 0.7473723

01:12:34.820 --> 01:12:35.880
trying to decrease

NOTE Confidence: 0.9239017

01:12:36.260 --> 01:12:38.820
recurrence, improve overall survival long

NOTE Confidence: 0.9239017

01:12:38.820 --> 01:12:40.660
term. But it's really hard

NOTE Confidence: 0.9239017

01:12:40.660 --> 01:12:42.260
just given the heterogeneity of

NOTE Confidence: 0.9239017

01:12:42.260 --> 01:12:44.180
this population too to really

NOTE Confidence: 0.9239017

01:12:44.180 --> 01:12:44.680
decipher

NOTE Confidence: 0.98411167

01:12:45.064 --> 01:12:46.925
who really needs additional therapy

NOTE Confidence: 0.98411167

01:12:46.985 --> 01:12:48.525
or who are we overtreating

NOTE Confidence: 0.98411167

01:12:48.744 --> 01:12:51.165
and inducing potentially permanent toxicities,

NOTE Confidence: 0.984079

01:12:51.784 --> 01:12:53.804
particularly with immune checkpoint inhibitors.

NOTE Confidence: 0.9630214

01:12:54.665 --> 01:12:56.025
These days too, we're also

NOTE Confidence: 0.9630214

01:12:56.025 --> 01:12:57.165
moving in the neoadjuvant

NOTE Confidence: 0.8888568

01:12:57.545 --> 01:12:58.985
space too, and Doctor. Roche

NOTE Confidence: 0.8888568

01:12:58.985 --> 01:12:59.885
has an energy

NOTE Confidence: 0.92428136

01:13:00.620 --> 01:13:02.479
neoadjuvant study trying to evaluate

NOTE Confidence: 0.92428136

01:13:02.540 --> 01:13:04.220
this in a re response

NOTE Confidence: 0.92428136

01:13:04.220 --> 01:13:04.720
adaptive,

NOTE Confidence: 0.9200072

01:13:05.420 --> 01:13:05.920
system.

NOTE Confidence: 0.95878524

01:13:07.020 --> 01:13:08.560
But, really, can we also

NOTE Confidence: 0.9761574

01:13:08.939 --> 01:13:11.100
help improve overall survival by

NOTE Confidence: 0.9761574

01:13:11.100 --> 01:13:13.600
moving systemic therapy earlier on?

NOTE Confidence: 0.9761574

01:13:13.895 --> 01:13:15.594
So where along the spectrum

NOTE Confidence: 0.9761574

01:13:15.655 --> 01:13:17.835
really does, GEP therapy,

NOTE Confidence: 0.9899535

01:13:18.614 --> 01:13:19.435
play a role?

NOTE Confidence: 0.98295665

01:13:19.895 --> 01:13:21.814
So as of right now,

NOTE Confidence: 0.98295665

01:13:21.814 --> 01:13:23.574
there really is no strong

NOTE Confidence: 0.98295665

01:13:23.574 --> 01:13:24.074
indication,

NOTE Confidence: 0.977514

01:13:25.655 --> 01:13:27.735
in clinical trial that really

NOTE Confidence: 0.977514

01:13:27.735 --> 01:13:28.235
supports

NOTE Confidence: 0.99907

01:13:28.614 --> 01:13:29.114
determining

NOTE Confidence: 0.98659974

01:13:29.590 --> 01:13:30.890
or utilizing GEP

NOTE Confidence: 0.9795043

01:13:31.350 --> 01:13:32.630
as a sole marker of

NOTE Confidence: 0.9795043

01:13:32.630 --> 01:13:33.990
whether or not we decide

NOTE Confidence: 0.9795043

01:13:33.990 --> 01:13:35.350
to do adjuvant therapy in

NOTE Confidence: 0.9795043

01:13:35.350 --> 01:13:36.090
these individuals.

NOTE Confidence: 0.94519246

01:13:36.710 --> 01:13:38.550
Again, there's some good clinical

NOTE Confidence: 0.94519246

01:13:38.550 --> 01:13:40.330
trials in progress that unfortunately

NOTE Confidence: 0.94519246

01:13:40.470 --> 01:13:41.670
we don't have the data

NOTE Confidence: 0.94519246

01:13:41.670 --> 01:13:43.574
yet on. So the NIVOMELA

NOTE Confidence: 0.95053977

01:13:43.875 --> 01:13:45.735
trial is currently ongoing,

NOTE Confidence: 0.82719094

01:13:46.354 --> 01:13:47.255
is still enrolling,

NOTE Confidence: 0.9354315

01:13:48.114 --> 01:13:50.114
but it's prospective randomized phase

NOTE Confidence: 0.9354315

01:13:50.114 --> 01:13:51.795
three study. The question here

NOTE Confidence: 0.9354315

01:13:51.795 --> 01:13:52.295
is,

NOTE Confidence: 0.8957777

01:13:52.675 --> 01:13:53.814
looking at melanogenics

NOTE Confidence: 0.9882852

01:13:55.074 --> 01:13:56.755
to see if that can,

NOTE Confidence: 0.99986786

01:13:57.235 --> 01:13:58.454
adequately predict

NOTE Confidence: 0.9946896

01:13:58.860 --> 01:14:00.300
in those individuals with high

NOTE Confidence: 0.9946896

01:14:00.300 --> 01:14:01.040
risk disease

NOTE Confidence: 0.9857713

01:14:01.580 --> 01:14:03.260
whether or not utilization of

NOTE Confidence: 0.9857713

01:14:03.260 --> 01:14:06.160
adjuvant nivolumab versus placebo improves

NOTE Confidence: 0.9857713

01:14:06.220 --> 01:14:07.900
outcomes in individuals with stage

NOTE Confidence: 0.9857713

01:14:07.900 --> 01:14:08.640
two melanoma.

NOTE Confidence: 0.9918573

01:14:09.260 --> 01:14:10.540
And so something for the

NOTE Confidence: 0.9918573

01:14:10.540 --> 01:14:11.740
future that we all should

NOTE Confidence: 0.9918573

01:14:11.740 --> 01:14:13.180
pay attention to once that

NOTE Confidence: 0.9918573

01:14:13.180 --> 01:14:14.594
data comes out and whether

NOTE Confidence: 0.9918573

01:14:14.594 --> 01:14:15.915
or not we can start

NOTE Confidence: 0.9918573

01:14:15.915 --> 01:14:17.435
integrating this in a more,

NOTE Confidence: 0.9962365

01:14:18.475 --> 01:14:20.875
evidence based fashion into our

NOTE Confidence: 0.9962365

01:14:20.875 --> 01:14:22.255
clinical decision making.

NOTE Confidence: 0.98500526

01:14:22.715 --> 01:14:23.835
Now the elephant in the

NOTE Confidence: 0.98500526

01:14:23.835 --> 01:14:25.594
room that we've not discussed

NOTE Confidence: 0.98500526

01:14:25.594 --> 01:14:27.354
yet this entire night is

NOTE Confidence: 0.98500526

01:14:27.354 --> 01:14:28.475
how do we factor in

NOTE Confidence: 0.98500526

01:14:28.475 --> 01:14:28.975
ctDNA

NOTE Confidence: 0.80720866

01:14:29.435 --> 01:14:29.935
too?

NOTE Confidence: 0.99727

01:14:30.520 --> 01:14:32.620
So there's more utilization

NOTE Confidence: 0.99948895

01:14:33.080 --> 01:14:33.979
for ctDNA

NOTE Confidence: 0.9449212

01:14:34.360 --> 01:14:35.660
in clinical management,

NOTE Confidence: 0.916785

01:14:36.200 --> 01:14:37.400
again, with,

NOTE Confidence: 0.97298235

01:14:37.960 --> 01:14:39.640
kind of caveats that this

NOTE Confidence: 0.97298235

01:14:39.640 --> 01:14:40.300
is also,

NOTE Confidence: 0.98898184

01:14:41.320 --> 01:14:42.300
semi understudied.

NOTE Confidence: 0.9970315

01:14:42.925 --> 01:14:44.365
There's a lot of ongoing

NOTE Confidence: 0.9970315

01:14:44.365 --> 01:14:45.885
clinical trials looking at this

NOTE Confidence: 0.9970315

01:14:45.885 --> 01:14:46.865
and risk stratifying

NOTE Confidence: 0.99983203

01:14:47.245 --> 01:14:47.745
individuals

NOTE Confidence: 0.9952395

01:14:48.365 --> 01:14:49.345
with ctDNA

NOTE Confidence: 0.9798251

01:14:49.725 --> 01:14:50.225
positivity,

NOTE Confidence: 0.9092684

01:14:50.685 --> 01:14:53.265
basically detectable circulating tumor DNA

NOTE Confidence: 0.9092684

01:14:53.325 --> 01:14:53.825
postoperative,

NOTE Confidence: 0.9757934

01:14:54.445 --> 01:14:56.205
and whether those individuals need

NOTE Confidence: 0.9757934

01:14:56.205 --> 01:14:58.110
adjuvant therapy versus those who

NOTE Confidence: 0.9757934

01:14:58.270 --> 01:14:59.330
clear their ctDNA

NOTE Confidence: 0.8761334

01:14:59.790 --> 01:15:00.530
post op.

NOTE Confidence: 0.97960395

01:15:01.310 --> 01:15:02.510
One of the best clinical

NOTE Confidence: 0.97960395

01:15:02.510 --> 01:15:03.869
trials that has been published

NOTE Confidence: 0.97960395

01:15:03.869 --> 01:15:05.150
to date in this setting

NOTE Confidence: 0.97960395

01:15:05.150 --> 01:15:06.750
actually occurred in stage two

NOTE Confidence: 0.97960395

01:15:06.750 --> 01:15:07.570
colon cancers.

NOTE Confidence: 0.8845035

01:15:08.189 --> 01:15:09.489
So this was the dynamic

NOTE Confidence: 0.9881503

01:15:09.790 --> 01:15:11.409
trial looking at ctDNA

NOTE Confidence: 0.99861336

01:15:11.949 --> 01:15:13.630
to guide the decision on

NOTE Confidence: 0.99861336

01:15:13.630 --> 01:15:15.445
whether adjuvant therapy needs to

NOTE Confidence: 0.99861336

01:15:15.445 --> 01:15:16.185
be pursued.

NOTE Confidence: 0.9952641

01:15:17.205 --> 01:15:18.885
The three year relapse free

NOTE Confidence: 0.9952641

01:15:18.885 --> 01:15:20.564
survival was eighty six point

NOTE Confidence: 0.9952641

01:15:20.564 --> 01:15:22.665
four percent amongst those with

NOTE Confidence: 0.9952641

01:15:22.725 --> 01:15:23.225
ctDNA

NOTE Confidence: 0.99732065

01:15:23.685 --> 01:15:24.185
positivity.

NOTE Confidence: 0.95593786

01:15:25.685 --> 01:15:27.125
It was really randomized to

NOTE Confidence: 0.95593786

01:15:27.125 --> 01:15:29.280
investigators' choice use that to

NOTE Confidence: 0.95593786

01:15:29.280 --> 01:15:30.719
guide decision making whether or

NOTE Confidence: 0.95593786

01:15:30.719 --> 01:15:32.500
not they received adjuvant chemotherapy.

NOTE Confidence: 0.9053566

01:15:32.880 --> 01:15:34.020
Again, the regimen,

NOTE Confidence: 0.8617992

01:15:34.719 --> 01:15:36.020
deferred to the investigator.

NOTE Confidence: 0.99875903

01:15:36.960 --> 01:15:38.560
This was versus ninety two

NOTE Confidence: 0.99875903

01:15:38.560 --> 01:15:39.540
point five percent

NOTE Confidence: 0.9359332

01:15:40.400 --> 01:15:40.900
of

NOTE Confidence: 0.974451

01:15:41.385 --> 01:15:43.864
recurrence free survival amongst the

NOTE Confidence: 0.974451

01:15:43.864 --> 01:15:45.704
CTD negative patients who did

NOTE Confidence: 0.974451

01:15:45.704 --> 01:15:47.485
not receive any additional therapy.

NOTE Confidence: 0.98511434

01:15:47.945 --> 01:15:48.925
So in the end,

NOTE Confidence: 0.9664839

01:15:49.465 --> 01:15:51.145
based on the CTD guided

NOTE Confidence: 0.9664839

01:15:51.145 --> 01:15:52.525
group, fewer patients,

NOTE Confidence: 0.99152505

01:15:53.304 --> 01:15:54.824
had to undergo and receive

NOTE Confidence: 0.99152505

01:15:54.824 --> 01:15:55.885
adjuvant chemotherapy,

NOTE Confidence: 0.997133

01:15:57.090 --> 01:15:59.650
and overall responses were very

NOTE Confidence: 0.997133

01:15:59.650 --> 01:16:00.150
similar.

NOTE Confidence: 0.8771532

01:16:01.330 --> 01:16:02.949
Now the COMBOAD

NOTE Confidence: 0.97331774

01:16:04.050 --> 01:16:05.969
trial was utilized to look

NOTE Confidence: 0.97331774

01:16:05.969 --> 01:16:08.229
at adjuvant dibrafnib and trametna

NOTE Confidence: 0.97331774

01:16:08.369 --> 01:16:10.389
for individuals with BRAF mutated

NOTE Confidence: 0.97331774

01:16:10.449 --> 01:16:10.949
melanomas

NOTE Confidence: 0.9988201

01:16:12.025 --> 01:16:12.825
for a year in the

NOTE Confidence: 0.9988201

01:16:12.825 --> 01:16:13.805
adjuvant setting.

NOTE Confidence: 0.97084653

01:16:14.265 --> 01:16:15.145
So what they did in

NOTE Confidence: 0.97084653

01:16:15.145 --> 01:16:17.245
this study was actually also

NOTE Confidence: 0.97084653

01:16:17.385 --> 01:16:18.985
evaluate, and they reported this

NOTE Confidence: 0.97084653

01:16:18.985 --> 01:16:19.485
separately,

NOTE Confidence: 0.8815334

01:16:19.785 --> 01:16:20.925
biomarker analysis,

NOTE Confidence: 0.9697492

01:16:21.625 --> 01:16:24.045
looking at ctDNA post resection.

NOTE Confidence: 0.9697492

01:16:24.185 --> 01:16:25.545
They found that in those

NOTE Confidence: 0.9697492

01:16:25.545 --> 01:16:26.045
individuals,

NOTE Confidence: 0.9886793

01:16:26.900 --> 01:16:28.740
post resection, thirteen percent of

NOTE Confidence: 0.9886793

01:16:28.740 --> 01:16:31.240
patients had still detectable ctDNA,

NOTE Confidence: 0.9383039

01:16:32.420 --> 01:16:34.180
and those were associated with

NOTE Confidence: 0.9383039

01:16:34.180 --> 01:16:35.640
worse survival outcomes.

NOTE Confidence: 0.89808446

01:16:36.100 --> 01:16:37.400
And so, again, ctDNA

NOTE Confidence: 0.9356928

01:16:37.700 --> 01:16:38.600
has been utilized

NOTE Confidence: 0.78654355

01:16:39.140 --> 01:16:41.265
and is emerging as prognostic

NOTE Confidence: 0.78654355

01:16:41.265 --> 01:16:41.765
outcome

NOTE Confidence: 0.93385124

01:16:42.065 --> 01:16:43.365
in individuals

NOTE Confidence: 0.89171565

01:16:44.064 --> 01:16:44.564
with,

NOTE Confidence: 0.7970657

01:16:44.945 --> 01:16:46.885
you know, high risk disease.

NOTE Confidence: 0.7970657

01:16:47.104 --> 01:16:47.604
Ultimately,

NOTE Confidence: 0.9763449

01:16:48.785 --> 01:16:49.525
if one

NOTE Confidence: 0.876571

01:16:49.905 --> 01:16:50.405
assay

NOTE Confidence: 0.8908091

01:16:51.025 --> 01:16:52.962
ctDNA versus GEP is going

NOTE Confidence: 0.8908091

01:16:52.962 --> 01:16:53.048
to be superior, inferior versus

NOTE Confidence: 0.8908091

01:16:53.048 --> 01:16:53.134
others yet to be determined.

NOTE Confidence: 0.8908091

01:16:53.134 --> 01:16:53.685
And I think really

NOTE Confidence: 0.75420374

01:16:54.305 --> 01:16:54.805
given

NOTE Confidence: 0.8592658

01:16:57.490 --> 01:16:58.630
determined. And I think really

NOTE Confidence: 0.8592658

01:16:58.930 --> 01:16:59.570
given kind of the limitations

NOTE Confidence: 0.8592658

01:16:59.570 --> 01:17:01.170
on some of the GEP

NOTE Confidence: 0.8592658

01:17:01.170 --> 01:17:02.630
assays and what they're designed

NOTE Confidence: 0.8592658

01:17:02.850 --> 01:17:04.210
to question whether or not

NOTE Confidence: 0.8592658

01:17:04.210 --> 01:17:06.229
that's sentinel lymph node biopsy

NOTE Confidence: 0.8592658

01:17:06.450 --> 01:17:07.990
versus overall prognostication,

NOTE Confidence: 0.9701539

01:17:09.650 --> 01:17:11.695
where that is aligned also

NOTE Confidence: 0.9701539

01:17:11.695 --> 01:17:12.814
kind of depends on the

NOTE Confidence: 0.9701539

01:17:12.814 --> 01:17:14.354
assay in question two.

NOTE Confidence: 0.9987117

01:17:15.535 --> 01:17:17.795
Whether or not GEP impacts

NOTE Confidence: 0.9715694

01:17:18.335 --> 01:17:19.715
how we surveil melanomas,

NOTE Confidence: 0.9827977

01:17:20.094 --> 01:17:21.215
also we're still in the

NOTE Confidence: 0.9827977

01:17:21.215 --> 01:17:22.655
primitive era of this as

NOTE Confidence: 0.9827977

01:17:22.655 --> 01:17:23.155
well.

NOTE Confidence: 0.9481043

01:17:24.130 --> 01:17:25.650
Really the guidelines and the

NOTE Confidence: 0.9481043

01:17:25.650 --> 01:17:26.150
consensus

NOTE Confidence: 0.9711341

01:17:26.530 --> 01:17:28.370
from individuals is that no

NOTE Confidence: 0.9711341

01:17:28.370 --> 01:17:29.810
changes really should be made

NOTE Confidence: 0.9711341

01:17:29.810 --> 01:17:30.630
at this point

NOTE Confidence: 0.9086638

01:17:31.090 --> 01:17:32.229
based on GEP,

NOTE Confidence: 0.86140627

01:17:33.170 --> 01:17:34.770
high risk versus low risk

NOTE Confidence: 0.86140627

01:17:34.770 --> 01:17:35.017
expression.

NOTE Confidence: 0.8851721

01:17:39.185 --> 01:17:40.725
Pathologic staging and histologic

NOTE Confidence: 0.68442476

01:17:41.345 --> 01:17:41.845
criteria.

NOTE Confidence: 0.94184434

01:17:42.305 --> 01:17:43.765
And that should always still

NOTE Confidence: 0.94184434

01:17:43.825 --> 01:17:45.665
take precedence over GEP as

NOTE Confidence: 0.94184434

01:17:45.665 --> 01:17:47.185
we're trying to learn more

NOTE Confidence: 0.94184434

01:17:47.185 --> 01:17:48.805
and gain more data, particularly

NOTE Confidence: 0.94184434

01:17:48.865 --> 01:17:50.945
prospective clinical trial data to

NOTE Confidence: 0.94184434

01:17:50.945 --> 01:17:52.520
see whether or not long

NOTE Confidence: 0.94184434

01:17:52.520 --> 01:17:53.420
term outcomes,

NOTE Confidence: 0.97335446

01:17:54.200 --> 01:17:55.100
hold true.

NOTE Confidence: 0.9457389

01:17:56.040 --> 01:17:57.640
Now kind of switching gears

NOTE Confidence: 0.9457389

01:17:57.640 --> 01:17:59.660
to the squamous cell carcinoma

NOTE Confidence: 0.9457389

01:17:59.800 --> 01:18:01.400
GEP space, so this is

NOTE Confidence: 0.9457389

01:18:01.400 --> 01:18:03.240
the CASEL Decision DX for

NOTE Confidence: 0.9457389

01:18:03.240 --> 01:18:04.460
squamous cell carcinomas.

NOTE Confidence: 0.8511521

01:18:05.145 --> 01:18:06.445
Now unlike melanomas,

NOTE Confidence: 0.9995577

01:18:07.224 --> 01:18:07.885
the testing

NOTE Confidence: 0.8092192

01:18:08.264 --> 01:18:10.364
of in this particular disease

NOTE Confidence: 0.9749864

01:18:10.905 --> 01:18:13.145
has is more mature compared

NOTE Confidence: 0.9749864

01:18:13.145 --> 01:18:14.045
to in melanoma.

NOTE Confidence: 0.9753873

01:18:14.505 --> 01:18:15.645
So this is the forty

NOTE Confidence: 0.9753873

01:18:15.704 --> 01:18:16.844
GEP panel.

NOTE Confidence: 0.8110061

01:18:17.570 --> 01:18:18.869
Again, as,

NOTE Confidence: 0.8938675

01:18:19.570 --> 01:18:21.090
my prior colleagues already has

NOTE Confidence: 0.8938675

01:18:21.090 --> 01:18:23.010
talked kind of three different

NOTE Confidence: 0.8938675

01:18:23.010 --> 01:18:25.570
categories, which help to predict

NOTE Confidence: 0.8938675

01:18:25.570 --> 01:18:27.110
metastasis free survival.

NOTE Confidence: 0.9942704

01:18:28.130 --> 01:18:29.570
Really kind of the three

NOTE Confidence: 0.9942704

01:18:29.570 --> 01:18:30.550
year metastasis

NOTE Confidence: 0.9989864

01:18:30.929 --> 01:18:31.590
free survival

NOTE Confidence: 0.9461652

01:18:32.415 --> 01:18:33.854
is much better in those

NOTE Confidence: 0.9461652

01:18:33.854 --> 01:18:34.995
with class one

NOTE Confidence: 0.95239985

01:18:35.375 --> 01:18:36.975
at ninety one percent versus

NOTE Confidence: 0.95239985

01:18:36.975 --> 01:18:38.495
class IIBs, which are about

NOTE Confidence: 0.95239985

01:18:38.495 --> 01:18:39.555
forty four percent.

NOTE Confidence: 0.80385834

01:18:40.495 --> 01:18:41.155
And again,

NOTE Confidence: 0.97138315

01:18:41.935 --> 01:18:43.854
as Doctor. Roche had mentioned,

NOTE Confidence: 0.97138315

01:18:43.854 --> 01:18:45.235
kind of the positive predictive

NOTE Confidence: 0.97138315

01:18:45.295 --> 01:18:47.295
value shows improvement over our

NOTE Confidence: 0.97138315

01:18:47.295 --> 01:18:47.795
standard

NOTE Confidence: 0.8321712

01:18:48.710 --> 01:18:49.210
AGCC

NOTE Confidence: 0.87790275

01:18:49.590 --> 01:18:50.550
staging and,

NOTE Confidence: 0.97979903

01:18:51.110 --> 01:18:53.030
Brigham and Women's Hospital staging

NOTE Confidence: 0.97979903

01:18:53.030 --> 01:18:54.410
systems at this point.

NOTE Confidence: 0.9619137

01:18:54.870 --> 01:18:56.229
So again, it was nice

NOTE Confidence: 0.9619137

01:18:56.229 --> 01:18:57.910
to see that comparison of

NOTE Confidence: 0.9619137

01:18:57.910 --> 01:18:58.410
GEP,

NOTE Confidence: 0.9981979

01:18:59.750 --> 01:19:01.930
versus traditional staging algorithms.

NOTE Confidence: 0.8886901

01:19:02.615 --> 01:19:04.375
Now the question here also

NOTE Confidence: 0.8886901

01:19:04.375 --> 01:19:05.415
is, you know, how do

NOTE Confidence: 0.8886901

01:19:05.415 --> 01:19:07.814
we utilize GEP, the Castle

NOTE Confidence: 0.8886901

01:19:07.814 --> 01:19:10.055
Bion Science testing for squamous

NOTE Confidence: 0.8886901

01:19:10.055 --> 01:19:11.735
cell carcinomas to determine whether

NOTE Confidence: 0.8886901

01:19:11.735 --> 01:19:13.335
or not individuals need adjuvant

NOTE Confidence: 0.8886901

01:19:13.335 --> 01:19:13.835
therapy?

NOTE Confidence: 0.995094

01:19:14.935 --> 01:19:16.715
There was actually two recent

NOTE Confidence: 0.74739397

01:19:17.415 --> 01:19:17.915
updates

NOTE Confidence: 0.9704809

01:19:18.479 --> 01:19:19.700
over the past year,

NOTE Confidence: 0.8518392

01:19:20.080 --> 01:19:21.760
C POST and keynote six

NOTE Confidence: 0.8518392

01:19:21.760 --> 01:19:23.439
thirty, looking at adjuvant anti

NOTE Confidence: 0.8518392

01:19:23.439 --> 01:19:24.880
PD-one therapy in these high

NOTE Confidence: 0.8518392

01:19:24.880 --> 01:19:25.380
risk

NOTE Confidence: 0.8285796

01:19:25.760 --> 01:19:27.200
individuals. So these are high

NOTE Confidence: 0.8285796

01:19:27.200 --> 01:19:27.667
risk generally by the MCCN

NOTE Confidence: 0.8285796

01:19:27.667 --> 01:19:27.852
criteria. The one utilized for

NOTE Confidence: 0.8285796

01:19:27.852 --> 01:19:28.500
C POST is kind of

NOTE Confidence: 0.75126046

01:19:29.760 --> 01:19:30.260
listed

NOTE Confidence: 0.9603317

01:19:38.594 --> 01:19:40.135
evasion, in transit metastases,

NOTE Confidence: 0.9771782

01:19:41.395 --> 01:19:42.695
recurrence, etcetera.

NOTE Confidence: 0.87435853

01:19:43.550 --> 01:19:44.750
And so really for C

NOTE Confidence: 0.87435853

01:19:44.750 --> 01:19:45.729
post trial,

NOTE Confidence: 0.9984891

01:19:46.110 --> 01:19:47.390
they did not report any

NOTE Confidence: 0.9984891

01:19:47.390 --> 01:19:48.370
GEP utilization

NOTE Confidence: 0.79617256

01:19:48.830 --> 01:19:50.290
nor did keynote sixthirty.

NOTE Confidence: 0.9659419

01:19:50.910 --> 01:19:52.110
So again, in this phase,

NOTE Confidence: 0.9659419

01:19:52.110 --> 01:19:53.150
it's kind of hard to

NOTE Confidence: 0.9659419

01:19:53.150 --> 01:19:55.150
compare the utility of adjuvant

NOTE Confidence: 0.9659419

01:19:55.150 --> 01:19:55.650
therapy,

NOTE Confidence: 0.9991098

01:19:56.430 --> 01:19:57.410
at this time.

NOTE Confidence: 0.85267043

01:19:58.335 --> 01:19:59.455
Now when we look at

NOTE Confidence: 0.85267043

01:19:59.455 --> 01:19:59.955
surveillance,

NOTE Confidence: 0.9725311

01:20:00.895 --> 01:20:02.175
we know that in terms

NOTE Confidence: 0.9725311

01:20:02.175 --> 01:20:03.935
of metastases, the class I

NOTE Confidence: 0.9725311

01:20:03.935 --> 01:20:05.455
patients had less than ten

NOTE Confidence: 0.9725311

01:20:05.455 --> 01:20:07.455
percent risk of metastases versus

NOTE Confidence: 0.9725311

01:20:07.455 --> 01:20:09.555
the class IIb. Those individuals

NOTE Confidence: 0.9900892

01:20:09.935 --> 01:20:11.215
had a greater than fifty

NOTE Confidence: 0.9900892

01:20:11.215 --> 01:20:12.595
percent risk of metastases.

NOTE Confidence: 0.9984567

01:20:13.620 --> 01:20:15.139
So when you have an

NOTE Confidence: 0.9984567

01:20:15.139 --> 01:20:15.639
AJCC

NOTE Confidence: 0.9274342

01:20:16.260 --> 01:20:17.880
that's a T3, T4

NOTE Confidence: 0.8769209

01:20:19.300 --> 01:20:20.739
or a similar kind of

NOTE Confidence: 0.8769209

01:20:20.739 --> 01:20:21.239
T2B,

NOTE Confidence: 0.83749896

01:20:21.860 --> 01:20:23.719
T3 and the, BHW

NOTE Confidence: 0.99166965

01:20:24.420 --> 01:20:24.920
classification,

NOTE Confidence: 0.93778485

01:20:26.245 --> 01:20:28.265
those are always kinda intermediate

NOTE Confidence: 0.93778485

01:20:28.325 --> 01:20:30.265
or high risk. It's really

NOTE Confidence: 0.93778485

01:20:30.325 --> 01:20:32.005
kinda discerning the T one,

NOTE Confidence: 0.93778485

01:20:32.005 --> 01:20:33.525
T twos and the T

NOTE Confidence: 0.93778485

01:20:33.525 --> 01:20:34.905
one, T two As,

NOTE Confidence: 0.92640567

01:20:36.085 --> 01:20:37.604
that really the class one,

NOTE Confidence: 0.92640567

01:20:37.604 --> 01:20:38.805
class two A, class two

NOTE Confidence: 0.92640567

01:20:38.805 --> 01:20:40.985
B designation kinda really helps

NOTE Confidence: 0.97830486

01:20:41.689 --> 01:20:44.110
to better delineate with granularity

NOTE Confidence: 0.9851469

01:20:44.650 --> 01:20:46.250
those individuals that will be

NOTE Confidence: 0.9851469

01:20:46.250 --> 01:20:47.710
at higher risk for developing

NOTE Confidence: 0.9851469

01:20:47.850 --> 01:20:49.790
metastatic disease in the future.

NOTE Confidence: 0.9851469

01:20:50.010 --> 01:20:51.610
And so really, it's kind

NOTE Confidence: 0.9851469

01:20:51.610 --> 01:20:53.550
of in those individuals where

NOTE Confidence: 0.9851469

01:20:53.725 --> 01:20:54.465
the discussion about

NOTE Confidence: 0.9970516

01:20:55.085 --> 01:20:56.785
how do you improve upon

NOTE Confidence: 0.85652137

01:20:58.045 --> 01:20:59.564
local disease control with the

NOTE Confidence: 0.85652137

01:20:59.564 --> 01:21:01.025
addition of adjuvant radiation,

NOTE Confidence: 0.9723699

01:21:01.965 --> 01:21:03.324
as Doctor. Young had alluded

NOTE Confidence: 0.9723699

01:21:03.324 --> 01:21:04.445
to, that really kind of

NOTE Confidence: 0.9723699

01:21:04.445 --> 01:21:04.945
makes

NOTE Confidence: 0.9778277

01:21:05.405 --> 01:21:06.844
a difference in long term

NOTE Confidence: 0.9778277

01:21:06.844 --> 01:21:07.905
clinical responses.

NOTE Confidence: 0.97704154

01:21:09.810 --> 01:21:11.270
So when we think about,

NOTE Confidence: 0.97071755

01:21:11.729 --> 01:21:13.969
surveillance in cutaneous squamous cell

NOTE Confidence: 0.97071755

01:21:13.969 --> 01:21:15.110
carcinomas too,

NOTE Confidence: 0.9751009

01:21:15.729 --> 01:21:16.770
this was kind of an

NOTE Confidence: 0.9751009

01:21:16.770 --> 01:21:18.949
interesting paradigm that was presented

NOTE Confidence: 0.9751009

01:21:19.170 --> 01:21:20.610
by Farberg et al,

NOTE Confidence: 0.9817447

01:21:21.090 --> 01:21:22.770
looking at those individuals that

NOTE Confidence: 0.9817447

01:21:22.770 --> 01:21:24.975
are classically considered high risk

NOTE Confidence: 0.9817447

01:21:25.055 --> 01:21:27.075
for cutaneous squamous cell carcinoma.

NOTE Confidence: 0.9817447

01:21:27.135 --> 01:21:29.215
So considering and taking into

NOTE Confidence: 0.9817447

01:21:29.215 --> 01:21:31.635
factor the forty GEP expression,

NOTE Confidence: 0.8924935

01:21:32.415 --> 01:21:33.615
and then looking at class

NOTE Confidence: 0.8924935

01:21:33.615 --> 01:21:35.235
one individuals. In these,

NOTE Confidence: 0.9975

01:21:36.015 --> 01:21:38.040
class one groups, we know

NOTE Confidence: 0.9975

01:21:38.040 --> 01:21:39.479
that these patients do well

NOTE Confidence: 0.9975

01:21:39.479 --> 01:21:39.979
overall

NOTE Confidence: 0.9880235

01:21:40.360 --> 01:21:41.260
based on,

NOTE Confidence: 0.99338096

01:21:42.760 --> 01:21:44.119
kind of their three year

NOTE Confidence: 0.99338096

01:21:44.119 --> 01:21:45.900
relapse free survival outcomes.

NOTE Confidence: 0.96890146

01:21:46.439 --> 01:21:48.219
So if you have someone

NOTE Confidence: 0.96890146

01:21:48.360 --> 01:21:49.639
who has is a class

NOTE Confidence: 0.96890146

01:21:49.639 --> 01:21:51.719
one, potentially fifty to sixty

NOTE Confidence: 0.96890146

01:21:51.719 --> 01:21:53.255
percent of those individuals

NOTE Confidence: 0.99672765

01:21:53.875 --> 01:21:54.854
could be spared,

NOTE Confidence: 0.9259147

01:21:55.475 --> 01:21:57.875
additional adjuvant anti PD one

NOTE Confidence: 0.9259147

01:21:57.875 --> 01:21:58.375
therapy.

NOTE Confidence: 0.99087274

01:21:58.675 --> 01:22:00.295
So you're minimizing toxicity.

NOTE Confidence: 0.9599793

01:22:00.755 --> 01:22:01.955
You know these patients are

NOTE Confidence: 0.9599793

01:22:01.955 --> 01:22:03.175
gonna do well overall.

NOTE Confidence: 0.9786164

01:22:04.275 --> 01:22:06.180
And so there is more

NOTE Confidence: 0.9786164

01:22:06.240 --> 01:22:08.160
equipoise than to say, okay,

NOTE Confidence: 0.9786164

01:22:08.160 --> 01:22:09.920
maybe these individuals don't need

NOTE Confidence: 0.9786164

01:22:09.920 --> 01:22:11.140
quite as much surveillance,

NOTE Confidence: 0.95960283

01:22:12.240 --> 01:22:14.580
and don't need standard, scheduled

NOTE Confidence: 0.95960283

01:22:14.640 --> 01:22:15.140
imaging.

NOTE Confidence: 0.9494646

01:22:15.920 --> 01:22:17.439
In those individuals then on

NOTE Confidence: 0.9494646

01:22:17.439 --> 01:22:18.640
the opposite side who have

NOTE Confidence: 0.9494646

01:22:18.640 --> 01:22:20.020
a class 2b signature,

NOTE Confidence: 0.97138304

01:22:20.425 --> 01:22:21.385
those are the ones that

NOTE Confidence: 0.97138304

01:22:21.385 --> 01:22:22.745
you really wanna focus on

NOTE Confidence: 0.97138304

01:22:22.745 --> 01:22:23.405
and maximizing,

NOTE Confidence: 0.98574275

01:22:24.345 --> 01:22:25.564
all the therapies

NOTE Confidence: 0.84991175

01:22:25.945 --> 01:22:26.445
upfront,

NOTE Confidence: 0.9916602

01:22:27.225 --> 01:22:28.285
to try to minimize,

NOTE Confidence: 0.9797325

01:22:28.905 --> 01:22:29.805
distant metastasis,

NOTE Confidence: 0.98542756

01:22:30.585 --> 01:22:31.085
recurrence.

NOTE Confidence: 0.9942581

01:22:31.785 --> 01:22:33.245
And so for these individuals,

NOTE Confidence: 0.95747674

01:22:33.625 --> 01:22:35.805
you wanna consider adjuvant radiation.

NOTE Confidence: 0.895512

01:22:36.720 --> 01:22:38.000
And this is what Doctor.

NOTE Confidence: 0.895512

01:22:38.000 --> 01:22:39.520
Young had already alluded to

NOTE Confidence: 0.895512

01:22:39.520 --> 01:22:40.660
too with these individuals,

NOTE Confidence: 0.9563445

01:22:41.360 --> 01:22:42.900
who had adjuvant radiation.

NOTE Confidence: 0.98469985

01:22:43.440 --> 01:22:45.120
Those individuals had a fifty

NOTE Confidence: 0.98469985

01:22:45.120 --> 01:22:46.800
percent improvement in five year

NOTE Confidence: 0.98469985

01:22:46.800 --> 01:22:48.340
metastasis free survival.

NOTE Confidence: 0.9350266

01:22:48.705 --> 01:22:49.665
And again, this was something

NOTE Confidence: 0.9350266

01:22:49.665 --> 01:22:50.785
that was not seen in

NOTE Confidence: 0.9350266

01:22:50.785 --> 01:22:51.905
class one or the class

NOTE Confidence: 0.9350266

01:22:51.905 --> 01:22:52.405
2a

NOTE Confidence: 0.7313836

01:22:53.185 --> 01:22:53.685
GPs.

NOTE Confidence: 0.94275886

01:22:54.385 --> 01:22:56.165
The moderate intensity, obviously,

NOTE Confidence: 0.9072256

01:22:56.705 --> 01:22:57.925
we consider,

NOTE Confidence: 0.9964083

01:22:58.865 --> 01:23:00.645
doing all the adjuvant treatments,

NOTE Confidence: 0.9170172

01:23:01.330 --> 01:23:02.470
the adjuvant radiation,

NOTE Confidence: 0.8738052

01:23:03.010 --> 01:23:04.330
but at that point too,

NOTE Confidence: 0.8738052

01:23:04.330 --> 01:23:05.810
it's all you're just also

NOTE Confidence: 0.8738052

01:23:05.810 --> 01:23:07.650
equicosed to talk about, kind

NOTE Confidence: 0.8738052

01:23:07.650 --> 01:23:09.330
of risk factors and on

NOTE Confidence: 0.8738052

01:23:09.330 --> 01:23:11.350
a patient per case basis,

NOTE Confidence: 0.96897334

01:23:11.650 --> 01:23:12.770
you know, what are their

NOTE Confidence: 0.96897334

01:23:12.770 --> 01:23:14.305
goals, what are their morbidities

NOTE Confidence: 0.96897334

01:23:14.445 --> 01:23:15.885
and trying to factor this

NOTE Confidence: 0.96897334

01:23:15.885 --> 01:23:17.505
in on a more personalized

NOTE Confidence: 0.96897334

01:23:17.725 --> 01:23:18.225
approach.

NOTE Confidence: 0.9930692

01:23:19.485 --> 01:23:20.525
So again, kind of the

NOTE Confidence: 0.9930692

01:23:20.525 --> 01:23:21.645
summary of all of this

NOTE Confidence: 0.9930692

01:23:21.645 --> 01:23:22.785
is that it's complicated.

NOTE Confidence: 0.9957953

01:23:23.965 --> 01:23:25.325
There's still a lot that

NOTE Confidence: 0.9957953

01:23:25.325 --> 01:23:26.365
we still have yet to

NOTE Confidence: 0.9957953

01:23:26.365 --> 01:23:28.385
learn in trying to integrate

NOTE Confidence: 0.96408576

01:23:28.989 --> 01:23:30.590
these new technologies in our

NOTE Confidence: 0.96408576

01:23:30.590 --> 01:23:31.489
clinical practice,

NOTE Confidence: 0.98916775

01:23:32.270 --> 01:23:33.550
a lot of clinical trials

NOTE Confidence: 0.98916775

01:23:33.550 --> 01:23:34.830
that are forthcoming that may

NOTE Confidence: 0.98916775

01:23:34.830 --> 01:23:36.270
help to elucidate these,

NOTE Confidence: 0.95256376

01:23:36.670 --> 01:23:37.810
questions and answers.

NOTE Confidence: 0.68650293

01:23:39.790 --> 01:23:40.929
But really,

NOTE Confidence: 0.9851989

01:23:41.469 --> 01:23:42.909
and, you know, trying to

NOTE Confidence: 0.9851989

01:23:42.909 --> 01:23:44.755
figure out how do we

NOTE Confidence: 0.9851989

01:23:44.755 --> 01:23:47.335
also then reconcile ctDNA data

NOTE Confidence: 0.9851989

01:23:47.395 --> 01:23:49.395
with GEP data to best

NOTE Confidence: 0.9851989

01:23:49.395 --> 01:23:50.695
guide decision making.

NOTE Confidence: 0.97110504

01:23:51.715 --> 01:23:53.335
You know, there may be

NOTE Confidence: 0.97110504

01:23:53.475 --> 01:23:53.975
forthcoming

NOTE Confidence: 0.8050505

01:23:54.755 --> 01:23:55.255
GEP

NOTE Confidence: 0.92289656

01:23:55.555 --> 01:23:56.835
like two point zero at

NOTE Confidence: 0.92289656

01:23:56.835 --> 01:23:57.575
some point

NOTE Confidence: 0.9919668

01:23:57.880 --> 01:23:59.400
that will also help not

NOTE Confidence: 0.9919668

01:23:59.400 --> 01:24:01.320
only look at metastases, local

NOTE Confidence: 0.9919668

01:24:01.320 --> 01:24:03.020
recurrence, lymph node positivity,

NOTE Confidence: 0.9764438

01:24:03.560 --> 01:24:05.340
but overall survival too.

NOTE Confidence: 0.9825855

01:24:06.040 --> 01:24:07.160
And so I know there's

NOTE Confidence: 0.9825855

01:24:07.160 --> 01:24:09.400
individuals already working on this

NOTE Confidence: 0.9825855

01:24:09.400 --> 01:24:10.140
and emerging

NOTE Confidence: 0.95196056

01:24:10.440 --> 01:24:12.620
technologies in this regard too.

NOTE Confidence: 0.9836533

01:24:13.604 --> 01:24:14.664
With that, I think

NOTE Confidence: 0.9931304

01:24:15.045 --> 01:24:16.344
we are done.

NOTE Confidence: 0.9465908

01:24:16.965 --> 01:24:17.465
So,

NOTE Confidence: 0.98543316

01:24:18.405 --> 01:24:19.604
let me stop sharing, and

NOTE Confidence: 0.98543316

01:24:19.604 --> 01:24:20.564
maybe we can go back

NOTE Confidence: 0.98543316

01:24:20.564 --> 01:24:21.764
to the chat if anyone

NOTE Confidence: 0.98543316

01:24:21.764 --> 01:24:22.744
has any questions.

NOTE Confidence: 0.817202

01:24:45.594 --> 01:24:46.094
Okay.

NOTE Confidence: 0.9614346

01:24:49.034 --> 01:24:49.675
We had,

NOTE Confidence: 0.97177094

01:24:50.554 --> 01:24:52.074
Barb Barbara Johnson had a

NOTE Confidence: 0.97177094

01:24:52.074 --> 01:24:53.675
question about how long the

NOTE Confidence: 0.97177094

01:24:53.675 --> 01:24:55.054
assays take to

NOTE Confidence: 0.8828219

01:24:55.810 --> 01:24:56.870
result to,

NOTE Confidence: 0.896507

01:24:57.330 --> 01:24:58.150
doctor Christiansen.

NOTE Confidence: 0.9858322

01:24:58.610 --> 01:24:59.090
Do you have a

NOTE Confidence: 0.9947289

01:25:00.210 --> 01:25:01.250
you've been using this, I

NOTE Confidence: 0.9947289

01:25:01.250 --> 01:25:02.550
think, a little bit more.

NOTE Confidence: 0.9947289

01:25:02.770 --> 01:25:04.130
Yeah. So it's it's usually

NOTE Confidence: 0.9947289

01:25:04.130 --> 01:25:05.030
about a week

NOTE Confidence: 0.9925448

01:25:05.410 --> 01:25:07.010
turnaround time, and most of

NOTE Confidence: 0.9925448

01:25:07.010 --> 01:25:09.505
that is from shipping. So

NOTE Confidence: 0.98539466

01:25:09.885 --> 01:25:11.505
the the assay is done

NOTE Confidence: 0.93790954

01:25:11.965 --> 01:25:13.885
on formalum fixed slides from

NOTE Confidence: 0.93790954

01:25:13.885 --> 01:25:14.945
the original biopsy,

NOTE Confidence: 0.99801123

01:25:15.724 --> 01:25:16.525
and that has to be

NOTE Confidence: 0.99801123

01:25:16.525 --> 01:25:17.965
shipped to the company. And

NOTE Confidence: 0.99801123

01:25:17.965 --> 01:25:19.085
then once they get it,

NOTE Confidence: 0.99801123

01:25:19.085 --> 01:25:19.965
then they can do that

NOTE Confidence: 0.99801123

01:25:19.965 --> 01:25:21.005
test within a day or

NOTE Confidence: 0.99801123

01:25:21.005 --> 01:25:21.505
so.

NOTE Confidence: 0.99615246

01:25:22.360 --> 01:25:23.640
So it's it's just the

NOTE Confidence: 0.99615246

01:25:23.640 --> 01:25:25.240
logistics of transferring it that

NOTE Confidence: 0.99615246

01:25:25.240 --> 01:25:26.040
takes a little bit of

NOTE Confidence: 0.99615246

01:25:26.040 --> 01:25:27.720
time. But since that's done

NOTE Confidence: 0.99615246

01:25:27.720 --> 01:25:30.060
on the original diagnostic biopsy,

NOTE Confidence: 0.99615246

01:25:30.280 --> 01:25:31.740
that can actually be initiated,

NOTE Confidence: 0.994789

01:25:32.680 --> 01:25:33.800
you know, while the patient

NOTE Confidence: 0.994789

01:25:33.800 --> 01:25:34.840
is getting set up for

NOTE Confidence: 0.994789

01:25:34.840 --> 01:25:36.460
their consultation and surgery.

NOTE Confidence: 0.92110854

01:25:40.945 --> 01:25:42.064
I have a question for

NOTE Confidence: 0.92110854

01:25:42.064 --> 01:25:43.684
doctor Christiansen maybe.

NOTE Confidence: 0.96717536

01:25:45.264 --> 01:25:47.125
Sure. In terms of these

NOTE Confidence: 0.96717536

01:25:47.184 --> 01:25:49.104
various assays, there's so many

NOTE Confidence: 0.96717536

01:25:49.104 --> 01:25:51.184
companies that offer their own

NOTE Confidence: 0.96717536

01:25:51.184 --> 01:25:51.684
proprietary

NOTE Confidence: 0.9509034

01:25:52.145 --> 01:25:52.645
assay.

NOTE Confidence: 0.9915508

01:25:53.830 --> 01:25:55.530
Sometimes tissue is quite precious.

NOTE Confidence: 0.9915508

01:25:55.590 --> 01:25:57.030
So if you commit to

NOTE Confidence: 0.9915508

01:25:57.030 --> 01:25:57.530
doing,

NOTE Confidence: 0.96075684

01:25:58.630 --> 01:25:59.610
you know, formalin

NOTE Confidence: 0.98582387

01:26:00.390 --> 01:26:02.550
submitting formalin fixed tissue to

NOTE Confidence: 0.98582387

01:26:02.550 --> 01:26:04.170
a company for one particular

NOTE Confidence: 0.98582387

01:26:04.229 --> 01:26:05.930
assay, for example, we do

NOTE Confidence: 0.98582387

01:26:06.070 --> 01:26:07.835
a lot of Natera ctDNA

NOTE Confidence: 0.98582387

01:26:08.135 --> 01:26:08.635
monitoring.

NOTE Confidence: 0.99352765

01:26:10.055 --> 01:26:11.335
Do any of these companies

NOTE Confidence: 0.99352765

01:26:11.335 --> 01:26:12.395
ever work together

NOTE Confidence: 0.9989667

01:26:13.094 --> 01:26:13.594
to

NOTE Confidence: 0.95984775

01:26:14.295 --> 01:26:15.114
kind of maximize

NOTE Confidence: 0.9234059

01:26:15.895 --> 01:26:17.435
the DNA and

NOTE Confidence: 0.8962195

01:26:18.375 --> 01:26:19.594
the kind of the RNA

NOTE Confidence: 0.8962195

01:26:19.655 --> 01:26:21.575
so that they get as

NOTE Confidence: 0.8962195

01:26:21.575 --> 01:26:22.075
much

NOTE Confidence: 0.9770368

01:26:22.479 --> 01:26:24.079
out of such little tissue,

NOTE Confidence: 0.9770368

01:26:24.079 --> 01:26:25.360
particularly if we're talking about

NOTE Confidence: 0.9770368

01:26:25.360 --> 01:26:27.139
trying to prioritize looking at

NOTE Confidence: 0.9770368

01:26:27.280 --> 01:26:28.260
comparing ctDNA

NOTE Confidence: 0.97381413

01:26:28.560 --> 01:26:30.479
gene expression profiling in some

NOTE Confidence: 0.97381413

01:26:30.479 --> 01:26:31.520
of these t one, t

NOTE Confidence: 0.97381413

01:26:31.520 --> 01:26:33.040
two tumors where there's not

NOTE Confidence: 0.97381413

01:26:33.040 --> 01:26:34.239
gonna be much to begin

NOTE Confidence: 0.97381413

01:26:34.239 --> 01:26:34.739
with.

NOTE Confidence: 0.97624373

01:26:36.555 --> 01:26:37.354
So I don't think I

NOTE Confidence: 0.97624373

01:26:37.354 --> 01:26:38.895
know enough to accurately,

NOTE Confidence: 0.96492445

01:26:39.195 --> 01:26:40.575
fully answer that question,

NOTE Confidence: 0.9782506

01:26:40.955 --> 01:26:43.115
but my guess is probably

NOTE Confidence: 0.9782506

01:26:43.115 --> 01:26:44.475
the answer is no. I

NOTE Confidence: 0.9782506

01:26:44.475 --> 01:26:45.995
think these companies are all

NOTE Confidence: 0.9782506

01:26:45.995 --> 01:26:46.495
independent,

NOTE Confidence: 0.9746799

01:26:47.275 --> 01:26:48.155
and they all do their

NOTE Confidence: 0.9746799

01:26:48.155 --> 01:26:49.275
own thing. I mean, I

NOTE Confidence: 0.9746799

01:26:49.275 --> 01:26:50.155
think, you know, you you

NOTE Confidence: 0.9746799

01:26:50.155 --> 01:26:51.835
presented the idea of using

NOTE Confidence: 0.9746799

01:26:51.835 --> 01:26:53.349
GEP GEP and ctDNA

NOTE Confidence: 0.98178136

01:26:53.729 --> 01:26:55.329
together in a prospective trial.

NOTE Confidence: 0.98178136

01:26:55.329 --> 01:26:56.530
And if that were going

NOTE Confidence: 0.98178136

01:26:56.530 --> 01:26:57.809
to happen, then, you know,

NOTE Confidence: 0.98178136

01:26:57.809 --> 01:26:58.689
they would have to work

NOTE Confidence: 0.98178136

01:26:58.689 --> 01:26:59.189
together.

NOTE Confidence: 0.9464754

01:27:00.050 --> 01:27:01.010
But I think short of

NOTE Confidence: 0.9464754

01:27:01.010 --> 01:27:03.030
that right now, everybody's independent.

NOTE Confidence: 0.9632113

01:27:05.344 --> 01:27:06.705
I I believe that's that's

NOTE Confidence: 0.9632113

01:27:06.705 --> 01:27:08.304
correct. And and, actually, I

NOTE Confidence: 0.9632113

01:27:08.304 --> 01:27:10.465
believe that the Signatera slash

NOTE Confidence: 0.9632113

01:27:10.465 --> 01:27:12.304
Natera company is working on

NOTE Confidence: 0.9632113

01:27:12.304 --> 01:27:12.965
their own

NOTE Confidence: 0.9932131

01:27:13.425 --> 01:27:13.925
GEP.

NOTE Confidence: 0.979887

01:27:14.545 --> 01:27:15.045
So,

NOTE Confidence: 0.9432562

01:27:15.745 --> 01:27:16.705
and and to the point

NOTE Confidence: 0.9432562

01:27:16.705 --> 01:27:17.525
made earlier,

NOTE Confidence: 0.99369514

01:27:18.010 --> 01:27:19.689
each one is proprietary. So

NOTE Confidence: 0.99369514

01:27:19.689 --> 01:27:21.370
there's a reason that the

NOTE Confidence: 0.99369514

01:27:21.370 --> 01:27:23.550
genes of interest don't overlap

NOTE Confidence: 0.94536185

01:27:24.330 --> 01:27:26.010
with many of these even

NOTE Confidence: 0.94536185

01:27:26.010 --> 01:27:27.310
though they're looking at

NOTE Confidence: 0.9862129

01:27:27.850 --> 01:27:29.689
melanoma, which I always find

NOTE Confidence: 0.9862129

01:27:29.689 --> 01:27:30.189
fascinating.

NOTE Confidence: 0.9702662

01:27:30.729 --> 01:27:32.635
And you'll, unfortunately, I don't

NOTE Confidence: 0.9702662

01:27:32.635 --> 01:27:33.915
know if we'll we'll ever

NOTE Confidence: 0.9702662

01:27:33.915 --> 01:27:34.715
be able to get head

NOTE Confidence: 0.9702662

01:27:34.715 --> 01:27:35.375
to head,

NOTE Confidence: 0.9998584

01:27:36.314 --> 01:27:36.814
comparisons

NOTE Confidence: 0.9703074

01:27:37.354 --> 01:27:38.795
for these because of the

NOTE Confidence: 0.9703074

01:27:38.795 --> 01:27:40.235
reason that you said our

NOTE Confidence: 0.9703074

01:27:40.235 --> 01:27:41.995
melanomas are small and the

NOTE Confidence: 0.9703074

01:27:41.995 --> 01:27:43.755
samples are precious. And,

NOTE Confidence: 0.9841064

01:27:44.475 --> 01:27:45.135
you know,

NOTE Confidence: 0.97101605

01:27:46.590 --> 01:27:48.110
it it'll be very, very

NOTE Confidence: 0.97101605

01:27:48.110 --> 01:27:50.030
interesting. But, again, we never

NOTE Confidence: 0.97101605

01:27:50.030 --> 01:27:52.110
thought companies would cooperate for

NOTE Confidence: 0.97101605

01:27:52.110 --> 01:27:53.950
systemic immune therapy and look

NOTE Confidence: 0.97101605

01:27:53.950 --> 01:27:55.490
where we are now. So

NOTE Confidence: 0.97101605

01:27:55.550 --> 01:27:56.450
I'm I'm hopeful.

NOTE Confidence: 0.86476105

01:28:01.275 --> 01:28:02.875
Maybe the sponsor of Iceman

NOTE Confidence: 0.86476105

01:28:02.875 --> 01:28:04.235
would like to do c

NOTE Confidence: 0.86476105

01:28:04.235 --> 01:28:04.974
two DNA.

NOTE Confidence: 0.9840501

01:28:06.715 --> 01:28:07.454
They might.

NOTE Confidence: 0.9283727

01:28:09.914 --> 01:28:10.795
We'll bring it up at

NOTE Confidence: 0.9283727

01:28:10.795 --> 01:28:12.414
the next investigators meeting.

NOTE Confidence: 0.99846584

01:28:14.770 --> 01:28:16.290
Alright. Well, for all of

NOTE Confidence: 0.99846584

01:28:16.290 --> 01:28:17.890
those folks, I can't believe

NOTE Confidence: 0.99846584

01:28:17.890 --> 01:28:19.010
how many people have stayed

NOTE Confidence: 0.99846584

01:28:19.010 --> 01:28:19.989
on the entire

NOTE Confidence: 0.9878246

01:28:20.290 --> 01:28:21.489
time. So thank you so

NOTE Confidence: 0.9878246

01:28:21.489 --> 01:28:23.090
much to your audience. Thank

NOTE Confidence: 0.9878246

01:28:23.090 --> 01:28:25.250
you for questions, and thank

NOTE Confidence: 0.9878246

01:28:25.250 --> 01:28:26.530
you to my colleagues that

NOTE Confidence: 0.9878246

01:28:26.530 --> 01:28:27.750
I have the pleasure

NOTE Confidence: 0.97305524

01:28:28.255 --> 01:28:29.614
to work with every day

NOTE Confidence: 0.97305524

01:28:29.614 --> 01:28:31.155
and pick their brain about

NOTE Confidence: 0.97305524

01:28:31.295 --> 01:28:32.435
just about anything.

NOTE Confidence: 0.99442005

01:28:33.215 --> 01:28:34.915
So thank you to everyone

NOTE Confidence: 0.9536131

01:28:35.375 --> 01:28:37.375
and, we're all open, very

NOTE Confidence: 0.9536131

01:28:37.375 --> 01:28:38.995
easy to find via email.

NOTE Confidence: 0.9536131

01:28:39.148 --> 01:28:40.748
If people had questions that

NOTE Confidence: 0.9536131

01:28:40.748 --> 01:28:42.188
they come up with, even

NOTE Confidence: 0.9536131

01:28:42.188 --> 01:28:42.988
for those of you who

NOTE Confidence: 0.9536131

01:28:42.988 --> 01:28:44.508
may be later viewing this

NOTE Confidence: 0.9536131

01:28:44.508 --> 01:28:46.108
on YouTube. So thank you

NOTE Confidence: 0.9536131

01:28:46.108 --> 01:28:47.488
and have a wonderful evening.