WEBVTT

NOTE duration: "01:28:04.108"


NOTE Confidence: 0.90831137

00:00:00.080 --> 00:00:00.900
Alright. Let's get

NOTE Confidence: 0.9344439

00:00:01.439 --> 00:00:03.040
started. Good eve good evening,

NOTE Confidence: 0.9344439

00:00:03.040 --> 00:00:04.000
everyone, and thank you for

NOTE Confidence: 0.9344439

00:00:04.000 --> 00:00:04.980
joining us for,

NOTE Confidence: 0.90911794

00:00:05.519 --> 00:00:06.799
the Center of GI Cancer,

NOTE Confidence: 0.90911794

00:00:06.799 --> 00:00:08.420
the CME webinar series,

NOTE Confidence: 0.87022793

00:00:09.519 --> 00:00:09.920
at the

NOTE Confidence: 0.91521573

00:00:10.719 --> 00:00:11.619
for the Gastroenterology

NOTE Confidence: 0.9673954

00:00:12.000 --> 00:00:14.385
Cancer segment. I'm Raghav Sundar.

NOTE Confidence: 0.9673954

00:00:14.525 --> 00:00:15.985
I'm a GI medical oncologist

NOTE Confidence: 0.9673954

00:00:16.125 --> 00:00:17.265
and leader of the Gastroesophageal

NOTE Confidence: 0.8855568

00:00:17.645 --> 00:00:18.465
Cancer Program.

NOTE Confidence: 0.998783

00:00:22.605 --> 00:00:23.585
These are my disclosures.

NOTE Confidence: 0.9678272

00:00:25.600 --> 00:00:26.560
So for the past few

NOTE Confidence: 0.9678272

00:00:26.560 --> 00:00:27.920
months, the Center for GI

NOTE Confidence: 0.9678272

00:00:27.920 --> 00:00:29.860
Cancers have had a webinar

NOTE Confidence: 0.9678272

00:00:29.920 --> 00:00:31.360
series. This is part three

NOTE Confidence: 0.9678272

00:00:31.360 --> 00:00:33.040
of this webinar series. In

NOTE Confidence: 0.9678272

00:00:33.040 --> 00:00:34.800
February, we had a GI

NOTE Confidence: 0.9678272

00:00:34.800 --> 00:00:36.340
oncology year in review.

NOTE Confidence: 0.9337723

00:00:36.800 --> 00:00:38.445
And in March with for

NOTE Confidence: 0.9337723

00:00:38.445 --> 00:00:40.365
Colorectal Cancer Awareness Month, we

NOTE Confidence: 0.9337723

00:00:40.365 --> 00:00:41.265
had the colorectal,

NOTE Confidence: 0.9110297

00:00:42.205 --> 00:00:43.805
series. And this month, we're

NOTE Confidence: 0.9110297

00:00:43.805 --> 00:00:44.705
gonna do Gastroesophageal

NOTE Confidence: 0.9580072

00:00:45.085 --> 00:00:46.605
Cancers as a part of

NOTE Confidence: 0.9580072

00:00:46.605 --> 00:00:47.265
the Gastroesophageal

NOTE Confidence: 0.99286616

00:00:47.645 --> 00:00:49.805
Cancer Awareness Month. And we

NOTE Confidence: 0.99286616

00:00:49.805 --> 00:00:51.245
have I'm I'm pleased to

NOTE Confidence: 0.99286616

00:00:51.245 --> 00:00:52.945
be joined by three fantastic

NOTE Confidence: 0.99286616

00:00:53.005 --> 00:00:53.505
speakers,

NOTE Confidence: 0.974794

00:00:54.170 --> 00:00:54.890
who will be talking to

NOTE Confidence: 0.974794

00:00:54.890 --> 00:00:56.329
us about different aspects of

NOTE Confidence: 0.974794

00:00:56.329 --> 00:00:57.629
the multimodal discipline

NOTE Confidence: 0.88927484

00:00:58.089 --> 00:00:58.670
discipline of,

NOTE Confidence: 0.9689319

00:01:00.730 --> 00:01:02.030
gastroesophageal cancers.

NOTE Confidence: 0.943831

00:01:02.489 --> 00:01:04.170
So I have, professor Dan

NOTE Confidence: 0.943831

00:01:04.170 --> 00:01:04.670
Boffa,

NOTE Confidence: 0.9550548

00:01:05.049 --> 00:01:06.409
who's a professor of surgery

NOTE Confidence: 0.9550548

00:01:06.409 --> 00:01:07.630
from thoracic oncology,

NOTE Confidence: 0.9264476

00:01:07.930 --> 00:01:08.970
who'll be talking to us

NOTE Confidence: 0.9264476

00:01:08.970 --> 00:01:09.209
about,

NOTE Confidence: 0.99576175

00:01:10.064 --> 00:01:10.965
surgical updates.

NOTE Confidence: 0.9792069

00:01:11.985 --> 00:01:12.384
I have,

NOTE Confidence: 0.96259516

00:01:12.944 --> 00:01:14.465
doctor Kevin Du, who's an

NOTE Confidence: 0.96259516

00:01:14.465 --> 00:01:16.384
associate professor from radiation oncology,

NOTE Confidence: 0.96259516

00:01:16.384 --> 00:01:17.825
who'll be updating us on

NOTE Confidence: 0.96259516

00:01:17.825 --> 00:01:20.325
the latest in radiation oncology

NOTE Confidence: 0.96259516

00:01:20.384 --> 00:01:21.125
for gastroesophageal

NOTE Confidence: 0.94130224

00:01:21.505 --> 00:01:22.005
cancers.

NOTE Confidence: 0.9519281

00:01:22.530 --> 00:01:24.050
And I also have, Doctor.

NOTE Confidence: 0.9519281

00:01:24.050 --> 00:01:25.490
Joanna Gibson, who's an associate

NOTE Confidence: 0.9519281

00:01:25.490 --> 00:01:27.090
professor of pathology, who'll be

NOTE Confidence: 0.9519281

00:01:27.090 --> 00:01:27.810
talking to us in the

NOTE Confidence: 0.9519281

00:01:27.810 --> 00:01:29.330
latest in the biomarkers of

NOTE Confidence: 0.9519281

00:01:29.330 --> 00:01:29.830
gastroesophageal

NOTE Confidence: 0.9967119

00:01:30.130 --> 00:01:30.630
cancers.

NOTE Confidence: 0.98521644

00:01:31.250 --> 00:01:32.290
And to get things started

NOTE Confidence: 0.98521644

00:01:32.290 --> 00:01:33.650
off, we'll start with Doctor.

NOTE Confidence: 0.98521644

00:01:33.650 --> 00:01:34.930
Gibson sharing with us a

NOTE Confidence: 0.98521644

00:01:34.930 --> 00:01:36.069
little bit about,

NOTE Confidence: 0.96539545

00:01:37.155 --> 00:01:38.834
what's up and new in,

NOTE Confidence: 0.96539545

00:01:39.155 --> 00:01:40.935
the pathology space for gastroesophageal

NOTE Confidence: 0.9846046

00:01:41.395 --> 00:01:43.415
cancers. Doctor Gibson, please.

NOTE Confidence: 0.95354015

00:01:43.955 --> 00:01:44.775
Thank you.

NOTE Confidence: 0.92012864

00:01:51.070 --> 00:01:51.570
So,

NOTE Confidence: 0.98455316

00:01:52.110 --> 00:01:53.070
as you can see, I

NOTE Confidence: 0.98455316

00:01:53.070 --> 00:01:54.450
went with a green background

NOTE Confidence: 0.98455316

00:01:54.509 --> 00:01:55.549
because it's spring, and I

NOTE Confidence: 0.98455316

00:01:55.549 --> 00:01:56.369
was inspired.

NOTE Confidence: 0.97015995

00:01:57.150 --> 00:01:58.670
So it's not a diss

NOTE Confidence: 0.97015995

00:01:58.670 --> 00:01:59.409
at Yale.

NOTE Confidence: 0.9765991

00:01:59.950 --> 00:02:01.250
The Yale blue is wonderful,

NOTE Confidence: 0.9765991

00:02:01.310 --> 00:02:02.509
but I thought this was

NOTE Confidence: 0.9765991

00:02:02.509 --> 00:02:03.009
appropriate.

NOTE Confidence: 0.9905089

00:02:03.549 --> 00:02:04.030
So,

NOTE Confidence: 0.99835664

00:02:04.509 --> 00:02:05.490
I have no disclosures.

NOTE Confidence: 0.9774804

00:02:06.625 --> 00:02:08.625
So just a broad, review

NOTE Confidence: 0.9774804

00:02:08.625 --> 00:02:09.764
on the role of pathology

NOTE Confidence: 0.9774804

00:02:09.825 --> 00:02:10.565
in GJ,

NOTE Confidence: 0.9888334

00:02:11.345 --> 00:02:11.845
adenocarcinomas.

NOTE Confidence: 0.8495019

00:02:13.264 --> 00:02:14.165
Obviously, pathology,

NOTE Confidence: 0.9523735

00:02:15.264 --> 00:02:15.745
does,

NOTE Confidence: 0.997952

00:02:16.065 --> 00:02:17.504
the tissue confirmation of the

NOTE Confidence: 0.997952

00:02:17.504 --> 00:02:18.004
diagnosis

NOTE Confidence: 0.981413

00:02:18.544 --> 00:02:19.764
by looking at biopsies.

NOTE Confidence: 0.96281815

00:02:20.540 --> 00:02:22.540
We help with, staging once

NOTE Confidence: 0.96281815

00:02:22.540 --> 00:02:24.139
a resection has occurred by

NOTE Confidence: 0.96281815

00:02:24.139 --> 00:02:24.639
reviewing

NOTE Confidence: 0.99438107

00:02:25.099 --> 00:02:26.220
the extent of the tumor

NOTE Confidence: 0.99438107

00:02:26.220 --> 00:02:28.000
and and, lymph nodes.

NOTE Confidence: 0.9793185

00:02:28.540 --> 00:02:30.000
We also assess metastases

NOTE Confidence: 0.9598723

00:02:30.379 --> 00:02:31.260
in a in a lot

NOTE Confidence: 0.9598723

00:02:31.260 --> 00:02:32.235
of different ways.

NOTE Confidence: 0.9963342

00:02:33.195 --> 00:02:34.395
And the main thing,

NOTE Confidence: 0.9990655

00:02:34.715 --> 00:02:35.835
that we sort of also

NOTE Confidence: 0.9990655

00:02:35.835 --> 00:02:37.435
contribute to that has impact

NOTE Confidence: 0.9990655

00:02:37.435 --> 00:02:38.715
on how patients are treated

NOTE Confidence: 0.9990655

00:02:38.715 --> 00:02:39.215
is

NOTE Confidence: 0.970469

00:02:39.514 --> 00:02:41.615
biomarker assessment. And in particular,

NOTE Confidence: 0.9987787

00:02:42.155 --> 00:02:43.675
I'm going to talk about

NOTE Confidence: 0.9987787

00:02:43.675 --> 00:02:44.895
the IHC biomarkers.

NOTE Confidence: 0.9998646

00:02:46.370 --> 00:02:46.870
So

NOTE Confidence: 0.9951751

00:02:47.570 --> 00:02:49.590
at, Yale, we perform

NOTE Confidence: 0.99985975

00:02:49.889 --> 00:02:51.110
IHC biomarkers

NOTE Confidence: 0.96420944

00:02:51.570 --> 00:02:52.230
at reflux,

NOTE Confidence: 0.9631422

00:02:53.490 --> 00:02:55.270
at diagnosis through a reflux

NOTE Confidence: 0.9631422

00:02:55.330 --> 00:02:57.330
pathway. So reflux meaning that

NOTE Confidence: 0.9631422

00:02:57.330 --> 00:02:59.330
we do it whenever we,

NOTE Confidence: 0.9631422

00:02:59.650 --> 00:03:00.850
have a diagnosis of a

NOTE Confidence: 0.9631422

00:03:00.850 --> 00:03:01.350
gastroesophageal

NOTE Confidence: 0.9690166

00:03:02.105 --> 00:03:02.605
adenocarcinoma.

NOTE Confidence: 0.99671525

00:03:03.625 --> 00:03:05.305
And whether that's primary at

NOTE Confidence: 0.99671525

00:03:05.305 --> 00:03:06.525
the site or metastatic,

NOTE Confidence: 0.9942913

00:03:07.224 --> 00:03:08.504
if that's what the diagnosis

NOTE Confidence: 0.9942913

00:03:08.504 --> 00:03:09.864
is, we will perform all

NOTE Confidence: 0.9942913

00:03:09.864 --> 00:03:11.245
four of these biomarkers,

NOTE Confidence: 0.9901354

00:03:13.385 --> 00:03:14.665
at whatever time of the

NOTE Confidence: 0.9901354

00:03:14.665 --> 00:03:15.784
diagnosis. And one of the

NOTE Confidence: 0.9901354

00:03:15.784 --> 00:03:17.165
reasons why is because,

NOTE Confidence: 0.9550551

00:03:18.389 --> 00:03:19.510
the percent of patients that

NOTE Confidence: 0.9550551

00:03:19.510 --> 00:03:20.709
present with stage three zero

NOTE Confidence: 0.9550551

00:03:20.709 --> 00:03:22.150
four disease at the time

NOTE Confidence: 0.9550551

00:03:22.150 --> 00:03:23.669
of diagnosis is pretty high,

NOTE Confidence: 0.9550551

00:03:23.669 --> 00:03:24.870
you know, gets into seventy

NOTE Confidence: 0.9550551

00:03:24.870 --> 00:03:26.650
percent or so for GJ

NOTE Confidence: 0.9550551

00:03:26.709 --> 00:03:27.849
cancers. And,

NOTE Confidence: 0.97827786

00:03:29.430 --> 00:03:30.550
and it it is helpful

NOTE Confidence: 0.97827786

00:03:30.550 --> 00:03:31.635
to have these biomarkers

NOTE Confidence: 0.95998764

00:03:32.194 --> 00:03:33.715
upfront so so patients can

NOTE Confidence: 0.95998764

00:03:33.715 --> 00:03:34.995
be triaged to the right

NOTE Confidence: 0.95998764

00:03:34.995 --> 00:03:36.135
treatment option.

NOTE Confidence: 0.97690743

00:03:36.754 --> 00:03:38.295
And while we perform IHC,

NOTE Confidence: 0.97690743

00:03:38.515 --> 00:03:40.215
we do use other techniques

NOTE Confidence: 0.97690743

00:03:40.355 --> 00:03:41.095
if necessary,

NOTE Confidence: 0.9254883

00:03:41.715 --> 00:03:42.215
for,

NOTE Confidence: 0.9982047

00:03:42.915 --> 00:03:44.135
assessment of

NOTE Confidence: 0.9755626

00:03:45.970 --> 00:03:47.910
confirmation or or other biomarkers

NOTE Confidence: 0.9755626

00:03:48.130 --> 00:03:49.570
as well. And those are

NOTE Confidence: 0.9755626

00:03:49.570 --> 00:03:50.770
through a, you know, slightly

NOTE Confidence: 0.9755626

00:03:50.770 --> 00:03:51.590
different pathway.

NOTE Confidence: 0.99618626

00:03:52.530 --> 00:03:53.330
So I'm just gonna go

NOTE Confidence: 0.99618626

00:03:53.330 --> 00:03:54.390
through each of these.

NOTE Confidence: 0.96194786

00:03:55.330 --> 00:03:56.530
The initial ones, I'll just

NOTE Confidence: 0.96194786

00:03:56.530 --> 00:03:57.970
kind of, walk through in

NOTE Confidence: 0.96194786

00:03:57.970 --> 00:03:59.570
an abridged way. So mismatch

NOTE Confidence: 0.96194786

00:03:59.570 --> 00:04:00.470
repair deficiency

NOTE Confidence: 0.98040855

00:04:01.125 --> 00:04:02.405
is the biomarker that I

NOTE Confidence: 0.98040855

00:04:02.405 --> 00:04:03.465
kinda like to say,

NOTE Confidence: 0.9786709

00:04:04.085 --> 00:04:05.225
has double duty,

NOTE Confidence: 0.9770133

00:04:05.685 --> 00:04:07.365
because it, it is used

NOTE Confidence: 0.9770133

00:04:07.365 --> 00:04:08.565
for a couple of different

NOTE Confidence: 0.9770133

00:04:08.565 --> 00:04:10.645
clinical contexts. The biological basis

NOTE Confidence: 0.9770133

00:04:10.645 --> 00:04:12.905
for targeted therapy is immunotherapy

NOTE Confidence: 0.9990396

00:04:13.205 --> 00:04:13.705
targeting

NOTE Confidence: 0.8187216

00:04:14.070 --> 00:04:15.270
PD one, PD l one

NOTE Confidence: 0.8187216

00:04:15.270 --> 00:04:15.770
pathway.

NOTE Confidence: 0.9776063

00:04:16.550 --> 00:04:18.089
And that's thought to occur

NOTE Confidence: 0.9776063

00:04:18.150 --> 00:04:18.650
because

NOTE Confidence: 0.9873716

00:04:19.190 --> 00:04:21.370
tumors with mismatch repair deficiency

NOTE Confidence: 0.9958381

00:04:21.670 --> 00:04:22.810
or MSI status

NOTE Confidence: 0.99199754

00:04:23.910 --> 00:04:24.410
have

NOTE Confidence: 0.9990619

00:04:24.790 --> 00:04:25.290
high

NOTE Confidence: 0.9209719

00:04:26.604 --> 00:04:27.504
tumor antigen,

NOTE Confidence: 0.98389107

00:04:28.125 --> 00:04:29.664
and can activate,

NOTE Confidence: 0.97675586

00:04:29.964 --> 00:04:31.805
the immune system. And so

NOTE Confidence: 0.97675586

00:04:31.805 --> 00:04:33.664
by using PDL one inhibition,

NOTE Confidence: 0.97675586

00:04:33.724 --> 00:04:35.004
we can sort of target,

NOTE Confidence: 0.97675586

00:04:35.324 --> 00:04:36.544
tumor cells for

NOTE Confidence: 0.92129195

00:04:38.380 --> 00:04:39.120
immune mediated,

NOTE Confidence: 0.9905714

00:04:39.580 --> 00:04:40.080
destruction.

NOTE Confidence: 0.98075086

00:04:40.700 --> 00:04:42.640
And, mismatch repair deficiency

NOTE Confidence: 0.9983678

00:04:43.100 --> 00:04:44.080
is predominantly

NOTE Confidence: 0.97528553

00:04:44.380 --> 00:04:45.360
tested using,

NOTE Confidence: 0.8499693

00:04:45.900 --> 00:04:46.400
IHC.

NOTE Confidence: 0.9841034

00:04:47.500 --> 00:04:48.540
But we do have other

NOTE Confidence: 0.9841034

00:04:48.540 --> 00:04:50.140
techniques that can also detect

NOTE Confidence: 0.9841034

00:04:50.140 --> 00:04:51.680
it. But MMR IHC

NOTE Confidence: 0.97476536

00:04:52.035 --> 00:04:54.375
is a widely available technique

NOTE Confidence: 0.97476536

00:04:54.515 --> 00:04:56.375
that most laboratories have,

NOTE Confidence: 0.9984474

00:04:57.154 --> 00:04:58.695
and we're able and it's

NOTE Confidence: 0.9645099

00:04:59.154 --> 00:05:00.615
fairly easy and reproducible.

NOTE Confidence: 0.95817804

00:05:02.115 --> 00:05:02.835
So it's,

NOTE Confidence: 0.98632693

00:05:03.475 --> 00:05:05.339
and it's fast. So we're

NOTE Confidence: 0.98632693

00:05:05.339 --> 00:05:06.540
able to do that, and

NOTE Confidence: 0.98632693

00:05:06.540 --> 00:05:07.500
that's one of the reasons

NOTE Confidence: 0.98632693

00:05:07.500 --> 00:05:08.460
why we start with that

NOTE Confidence: 0.98632693

00:05:08.460 --> 00:05:08.960
one.

NOTE Confidence: 0.9773504

00:05:10.380 --> 00:05:12.060
And then, you know, how

NOTE Confidence: 0.9773504

00:05:12.060 --> 00:05:13.580
often I'm just gonna move

NOTE Confidence: 0.9773504

00:05:13.580 --> 00:05:14.560
one of the panels

NOTE Confidence: 0.95821255

00:05:15.900 --> 00:05:17.020
up to my other screen

NOTE Confidence: 0.95821255

00:05:17.020 --> 00:05:18.540
here. Excuse me for just

NOTE Confidence: 0.95821255

00:05:18.540 --> 00:05:19.199
one moment.

NOTE Confidence: 0.91719997

00:05:22.005 --> 00:05:22.325
And,

NOTE Confidence: 0.95151645

00:05:24.565 --> 00:05:26.505
how how often is, MMRD

NOTE Confidence: 0.9720499

00:05:26.885 --> 00:05:28.105
found in esophageal,

NOTE Confidence: 0.98699015

00:05:28.565 --> 00:05:30.005
and gastric cancers? It's not

NOTE Confidence: 0.98699015

00:05:30.005 --> 00:05:32.105
very common. In one study,

NOTE Confidence: 0.9992637

00:05:32.565 --> 00:05:33.065
from

NOTE Confidence: 0.9838263

00:05:33.610 --> 00:05:34.970
twenty sixteen, they found seven

NOTE Confidence: 0.9838263

00:05:34.970 --> 00:05:36.110
percent. I recently

NOTE Confidence: 0.98082536

00:05:36.890 --> 00:05:38.510
reviewed a Yale cohort,

NOTE Confidence: 0.9673039

00:05:40.250 --> 00:05:42.110
from twenty eighteen to,

NOTE Confidence: 0.9880874

00:05:42.490 --> 00:05:43.610
twenty twenty four, and we

NOTE Confidence: 0.9880874

00:05:43.610 --> 00:05:44.970
found about eleven percent in

NOTE Confidence: 0.9880874

00:05:44.970 --> 00:05:46.185
stomach cancer and

NOTE Confidence: 0.9745192

00:05:46.745 --> 00:05:48.125
a lot less in esophageal

NOTE Confidence: 0.9745192

00:05:48.345 --> 00:05:50.185
GJ cancers. But it is

NOTE Confidence: 0.9745192

00:05:50.185 --> 00:05:51.245
an important biomarker,

NOTE Confidence: 0.97731537

00:05:52.185 --> 00:05:53.464
that we need to identify

NOTE Confidence: 0.97731537

00:05:53.464 --> 00:05:54.505
because it does have this

NOTE Confidence: 0.97731537

00:05:54.505 --> 00:05:55.005
targeted

NOTE Confidence: 0.90288496

00:05:55.464 --> 00:05:56.205
targeted therapy

NOTE Confidence: 0.9995589

00:05:57.385 --> 00:05:57.885
option.

NOTE Confidence: 0.69215304

00:05:59.169 --> 00:05:59.669
Another

NOTE Confidence: 0.98079324

00:05:59.970 --> 00:06:01.889
biomarker is HER2, and that's

NOTE Confidence: 0.98079324

00:06:01.889 --> 00:06:03.889
the old reliable biomarker. And

NOTE Confidence: 0.98079324

00:06:03.889 --> 00:06:05.669
the basis for targeted therapy

NOTE Confidence: 0.98079324

00:06:05.810 --> 00:06:06.470
is that,

NOTE Confidence: 0.9948435

00:06:07.089 --> 00:06:09.330
some tumor cells will have

NOTE Confidence: 0.9948435

00:06:09.330 --> 00:06:10.710
overexpression of HER2

NOTE Confidence: 0.92335755

00:06:11.250 --> 00:06:12.529
on their surface, and,

NOTE Confidence: 0.9993231

00:06:12.930 --> 00:06:14.495
this can be targeted

NOTE Confidence: 0.82187974

00:06:15.035 --> 00:06:16.095
using antibodies

NOTE Confidence: 0.9976213

00:06:16.555 --> 00:06:18.255
or antibody drug conjugates.

NOTE Confidence: 0.98452663

00:06:20.714 --> 00:06:22.154
And, again, we use a

NOTE Confidence: 0.98452663

00:06:22.154 --> 00:06:23.455
method of IHC.

NOTE Confidence: 0.95738316

00:06:24.075 --> 00:06:26.154
That's the main method of

NOTE Confidence: 0.95738316

00:06:26.154 --> 00:06:26.654
finding

NOTE Confidence: 0.52814007

00:06:27.035 --> 00:06:27.535
this

NOTE Confidence: 0.99892807

00:06:30.800 --> 00:06:31.300
biomarker

NOTE Confidence: 0.9721018

00:06:32.480 --> 00:06:34.320
on tumor cells. And in

NOTE Confidence: 0.9721018

00:06:34.320 --> 00:06:36.000
terms of how often we

NOTE Confidence: 0.9721018

00:06:36.000 --> 00:06:38.400
see it, probably seen in

NOTE Confidence: 0.9721018

00:06:38.400 --> 00:06:38.900
about,

NOTE Confidence: 0.9445411

00:06:40.800 --> 00:06:42.960
fifty to sixty percent of,

NOTE Confidence: 0.935698

00:06:43.685 --> 00:06:45.125
GJ cancers. Kind of depends

NOTE Confidence: 0.935698

00:06:45.125 --> 00:06:46.245
on which study you read,

NOTE Confidence: 0.935698

00:06:46.245 --> 00:06:47.065
what cohort.

NOTE Confidence: 0.989855

00:06:47.525 --> 00:06:49.045
It's been, this has been

NOTE Confidence: 0.989855

00:06:49.045 --> 00:06:50.964
a biomarker that has been

NOTE Confidence: 0.989855

00:06:50.964 --> 00:06:52.404
in practice for a number

NOTE Confidence: 0.989855

00:06:52.404 --> 00:06:53.365
of years, and you can

NOTE Confidence: 0.989855

00:06:53.365 --> 00:06:55.045
you can see that the

NOTE Confidence: 0.989855

00:06:55.045 --> 00:06:56.665
use of, this biomarker,

NOTE Confidence: 0.9994832

00:06:57.445 --> 00:06:57.945
expression

NOTE Confidence: 0.9882105

00:06:58.390 --> 00:07:00.390
testing has increased from, you

NOTE Confidence: 0.9882105

00:07:00.390 --> 00:07:02.230
know, ten, fifteen years ago

NOTE Confidence: 0.9882105

00:07:02.230 --> 00:07:02.710
to,

NOTE Confidence: 0.999225

00:07:03.910 --> 00:07:04.650
more recently.

NOTE Confidence: 0.97302806

00:07:05.750 --> 00:07:07.750
And so we have a

NOTE Confidence: 0.97302806

00:07:07.750 --> 00:07:09.910
IHC component, and we will

NOTE Confidence: 0.97302806

00:07:09.910 --> 00:07:12.230
perform FISH testing if, the

NOTE Confidence: 0.97302806

00:07:12.230 --> 00:07:14.074
IHC shows a two plus

NOTE Confidence: 0.9898527

00:07:14.455 --> 00:07:16.055
pattern. And the exciting thing

NOTE Confidence: 0.9898527

00:07:16.055 --> 00:07:17.335
about HER2 is that even

NOTE Confidence: 0.9898527

00:07:17.335 --> 00:07:18.134
though it's been around for

NOTE Confidence: 0.9898527

00:07:18.134 --> 00:07:19.014
a long time and we've

NOTE Confidence: 0.9898527

00:07:19.014 --> 00:07:20.134
been able to target it

NOTE Confidence: 0.9898527

00:07:20.134 --> 00:07:21.995
using monoclonal antibodies,

NOTE Confidence: 0.98378515

00:07:22.535 --> 00:07:23.675
now there is,

NOTE Confidence: 0.77282774

00:07:24.134 --> 00:07:24.634
newer,

NOTE Confidence: 0.9858191

00:07:25.095 --> 00:07:26.694
data coming out that,

NOTE Confidence: 0.923552

00:07:27.095 --> 00:07:27.595
the

NOTE Confidence: 0.99728346

00:07:27.900 --> 00:07:28.800
antibody conjugates

NOTE Confidence: 0.9804108

00:07:29.820 --> 00:07:31.180
can use can be also

NOTE Confidence: 0.9804108

00:07:31.180 --> 00:07:31.680
used,

NOTE Confidence: 0.97055274

00:07:32.300 --> 00:07:34.220
in even, patients that have

NOTE Confidence: 0.97055274

00:07:34.220 --> 00:07:35.120
HER2 low,

NOTE Confidence: 0.99607414

00:07:35.820 --> 00:07:37.100
one plus or two plus

NOTE Confidence: 0.99607414

00:07:37.100 --> 00:07:37.600
findings.

NOTE Confidence: 0.99572474

00:07:37.980 --> 00:07:39.100
So it it is something

NOTE Confidence: 0.99572474

00:07:39.100 --> 00:07:40.060
that is going to be

NOTE Confidence: 0.99572474

00:07:40.060 --> 00:07:41.580
able to be expanded to

NOTE Confidence: 0.99572474

00:07:41.580 --> 00:07:42.880
other, patients.

NOTE Confidence: 0.9572923

00:07:45.215 --> 00:07:46.254
PDL one. I wish I

NOTE Confidence: 0.9572923

00:07:46.254 --> 00:07:47.854
could stop talking about PDL

NOTE Confidence: 0.9572923

00:07:47.854 --> 00:07:48.354
one.

NOTE Confidence: 0.99793065

00:07:48.735 --> 00:07:50.014
This is the problem child

NOTE Confidence: 0.99793065

00:07:50.014 --> 00:07:51.314
for the IHC biomarkers.

NOTE Confidence: 0.97878194

00:07:51.854 --> 00:07:53.615
The biological basis for targeted

NOTE Confidence: 0.97878194

00:07:53.615 --> 00:07:54.735
therapy is the same.

NOTE Confidence: 0.97717226

00:07:55.375 --> 00:07:57.155
It's very similar to MMR

NOTE Confidence: 0.9120655

00:07:57.775 --> 00:07:59.880
where, blockade of the PDL

NOTE Confidence: 0.9120655

00:07:59.880 --> 00:08:02.540
one, PD one pathway can,

NOTE Confidence: 0.7602568

00:08:04.919 --> 00:08:05.419
activate,

NOTE Confidence: 0.9969066

00:08:05.960 --> 00:08:07.900
the immune system to eliminate

NOTE Confidence: 0.9969066

00:08:07.960 --> 00:08:08.780
tumor cells.

NOTE Confidence: 0.9728731

00:08:09.320 --> 00:08:11.660
We use the, PDL one

NOTE Confidence: 0.97828597

00:08:13.575 --> 00:08:14.775
twenty two c three,

NOTE Confidence: 0.9759977

00:08:15.255 --> 00:08:16.795
antibody, which is the FDA

NOTE Confidence: 0.9759977

00:08:16.935 --> 00:08:17.435
approved,

NOTE Confidence: 0.87533945

00:08:17.815 --> 00:08:18.315
method.

NOTE Confidence: 0.9702979

00:08:19.015 --> 00:08:19.495
And,

NOTE Confidence: 0.9783713

00:08:19.895 --> 00:08:21.575
we perform what's called the

NOTE Confidence: 0.9783713

00:08:21.575 --> 00:08:23.115
CPS or combined positive,

NOTE Confidence: 0.9944749

00:08:23.575 --> 00:08:25.255
score. So that's the total

NOTE Confidence: 0.9944749

00:08:25.255 --> 00:08:26.615
number of PDL one staining

NOTE Confidence: 0.9944749

00:08:26.615 --> 00:08:27.975
cells in a tumor section

NOTE Confidence: 0.9944749

00:08:27.975 --> 00:08:29.590
that includes tumor cells, mononuclear

NOTE Confidence: 0.9611945

00:08:30.210 --> 00:08:32.290
inflammatory cells over the total

NOTE Confidence: 0.9611945

00:08:32.290 --> 00:08:33.570
number of tumor cells times

NOTE Confidence: 0.9611945

00:08:33.570 --> 00:08:34.390
one hundred.

NOTE Confidence: 0.98733526

00:08:35.090 --> 00:08:35.590
And,

NOTE Confidence: 0.94194007

00:08:36.050 --> 00:08:37.590
the problem is that,

NOTE Confidence: 0.9912446

00:08:39.890 --> 00:08:42.470
the FDA approved assay is

NOTE Confidence: 0.978229

00:08:43.524 --> 00:08:45.684
is, the positivity cutoff is

NOTE Confidence: 0.978229

00:08:45.684 --> 00:08:47.285
determined to be CPS greater

NOTE Confidence: 0.978229

00:08:47.285 --> 00:08:48.024
than one.

NOTE Confidence: 0.9832333

00:08:48.885 --> 00:08:49.865
But in trials,

NOTE Confidence: 0.9811099

00:08:50.404 --> 00:08:51.925
in certain trials, CPS greater

NOTE Confidence: 0.9811099

00:08:51.925 --> 00:08:53.225
than five was actually,

NOTE Confidence: 0.9694088

00:08:54.404 --> 00:08:55.785
much more, reliable

NOTE Confidence: 0.93306255

00:08:56.165 --> 00:08:56.665
and,

NOTE Confidence: 0.9448706

00:08:57.045 --> 00:08:57.545
effective.

NOTE Confidence: 0.99573326

00:08:57.925 --> 00:08:58.584
And so

NOTE Confidence: 0.9445783

00:08:59.220 --> 00:09:00.660
it's it's difficult. And the

NOTE Confidence: 0.9445783

00:09:00.660 --> 00:09:02.120
CPS score of one,

NOTE Confidence: 0.95181733

00:09:02.740 --> 00:09:04.740
is quite subtle, and there

NOTE Confidence: 0.95181733

00:09:04.740 --> 00:09:06.100
have been umpteen number of

NOTE Confidence: 0.95181733

00:09:06.100 --> 00:09:07.559
studies showing that pathologists

NOTE Confidence: 0.9902722

00:09:07.940 --> 00:09:09.300
are really not very good

NOTE Confidence: 0.9902722

00:09:09.300 --> 00:09:10.199
at being reproducible,

NOTE Confidence: 0.96482563

00:09:11.455 --> 00:09:11.955
across,

NOTE Confidence: 0.9624893

00:09:12.415 --> 00:09:13.615
pathologists. And one of the

NOTE Confidence: 0.9624893

00:09:13.615 --> 00:09:15.054
most recent papers on that

NOTE Confidence: 0.9624893

00:09:15.054 --> 00:09:16.195
is from our group,

NOTE Confidence: 0.7565749

00:09:16.975 --> 00:09:18.495
David Rem and Sujian Zhang

NOTE Confidence: 0.7565749

00:09:18.495 --> 00:09:20.755
group who are, our pathologists

NOTE Confidence: 0.7565749

00:09:20.895 --> 00:09:22.255
here who've looked at that.

NOTE Confidence: 0.9886328

00:09:22.575 --> 00:09:23.774
It is more reliable at

NOTE Confidence: 0.9886328

00:09:23.774 --> 00:09:25.270
the higher cutoffs. So, you

NOTE Confidence: 0.9886328

00:09:25.270 --> 00:09:26.550
know, CPS of five or

NOTE Confidence: 0.9886328

00:09:26.550 --> 00:09:28.170
more is probably more reliable

NOTE Confidence: 0.9886328

00:09:28.309 --> 00:09:28.970
as a result.

NOTE Confidence: 0.9575868

00:09:29.429 --> 00:09:30.710
And that could explain this

NOTE Confidence: 0.9575868

00:09:30.710 --> 00:09:31.450
this variability,

NOTE Confidence: 0.99849796

00:09:31.990 --> 00:09:33.190
could explain some of the

NOTE Confidence: 0.99849796

00:09:33.190 --> 00:09:34.170
lack of efficacy,

NOTE Confidence: 0.9496925

00:09:34.710 --> 00:09:35.210
for,

NOTE Confidence: 0.99949694

00:09:35.830 --> 00:09:36.330
trials

NOTE Confidence: 0.9351942

00:09:36.710 --> 00:09:37.529
in this setting.

NOTE Confidence: 0.95940655

00:09:39.135 --> 00:09:40.654
So claudan eighteen is the

NOTE Confidence: 0.95940655

00:09:40.654 --> 00:09:41.795
new kid on the block,

NOTE Confidence: 0.9940329

00:09:42.255 --> 00:09:43.315
and I'm going to

NOTE Confidence: 0.9885403

00:09:43.774 --> 00:09:44.495
talk about this in a

NOTE Confidence: 0.9885403

00:09:44.495 --> 00:09:46.195
little bit more detail. So,

NOTE Confidence: 0.9974685

00:09:46.735 --> 00:09:49.315
basically, claudan eighteen is a

NOTE Confidence: 0.9718821

00:09:50.350 --> 00:09:50.850
protein,

NOTE Confidence: 0.8938904

00:09:51.150 --> 00:09:53.150
that's a transmembrane protein that,

NOTE Confidence: 0.8938904

00:09:53.390 --> 00:09:54.770
forms the tight junction

NOTE Confidence: 0.96643555

00:09:55.550 --> 00:09:57.230
between cells. And normally, in

NOTE Confidence: 0.96643555

00:09:57.230 --> 00:09:58.850
the normal tissues, it's expressed,

NOTE Confidence: 0.96643555

00:09:59.070 --> 00:10:00.030
and you can see that

NOTE Confidence: 0.96643555

00:10:00.030 --> 00:10:01.230
it's in the tight junctions

NOTE Confidence: 0.96643555

00:10:01.230 --> 00:10:03.309
between the epithelial cells. But

NOTE Confidence: 0.96643555

00:10:03.309 --> 00:10:05.090
once, cancer cell,

NOTE Confidence: 0.94696593

00:10:08.804 --> 00:10:10.165
is, you know, goes through

NOTE Confidence: 0.94696593

00:10:10.165 --> 00:10:10.665
carcinogenesis,

NOTE Confidence: 0.9796794

00:10:10.965 --> 00:10:12.005
becomes a cancer cell, the

NOTE Confidence: 0.9796794

00:10:12.005 --> 00:10:14.184
claudin eighteen, can be retained

NOTE Confidence: 0.9796794

00:10:14.245 --> 00:10:15.205
on the surface of those

NOTE Confidence: 0.9796794

00:10:15.205 --> 00:10:16.404
cells, and it is also

NOTE Confidence: 0.9796794

00:10:16.404 --> 00:10:18.165
exposed because the tumor cells

NOTE Confidence: 0.9796794

00:10:18.165 --> 00:10:19.100
no longer stick to each

NOTE Confidence: 0.9796794

00:10:19.100 --> 00:10:20.140
other in the same way

NOTE Confidence: 0.9796794

00:10:20.140 --> 00:10:22.480
as native epithelial cells.

NOTE Confidence: 0.85140157

00:10:23.020 --> 00:10:23.520
And,

NOTE Confidence: 0.9723533

00:10:25.020 --> 00:10:26.540
and then looking at more

NOTE Confidence: 0.9723533

00:10:26.540 --> 00:10:27.840
detail at the protein,

NOTE Confidence: 0.97165424

00:10:28.460 --> 00:10:30.060
there's a loop, with a

NOTE Confidence: 0.97165424

00:10:30.060 --> 00:10:31.660
couple of binding sites where

NOTE Confidence: 0.97165424

00:10:31.660 --> 00:10:33.820
antibodies can be, used to

NOTE Confidence: 0.97165424

00:10:33.820 --> 00:10:35.384
target that particular,

NOTE Confidence: 0.9803566

00:10:37.444 --> 00:10:37.944
protein.

NOTE Confidence: 0.979602

00:10:39.605 --> 00:10:40.105
And,

NOTE Confidence: 0.9926457

00:10:40.485 --> 00:10:41.464
in terms of,

NOTE Confidence: 0.9742347

00:10:42.245 --> 00:10:43.125
what do we know about

NOTE Confidence: 0.9742347

00:10:43.125 --> 00:10:45.125
expression of claudine eighteen point

NOTE Confidence: 0.9742347

00:10:45.125 --> 00:10:46.725
two in esophagus or,

NOTE Confidence: 0.8807931

00:10:47.204 --> 00:10:48.184
GJ cancers?

NOTE Confidence: 0.8778198

00:10:48.565 --> 00:10:48.884
And,

NOTE Confidence: 0.9750722

00:10:50.790 --> 00:10:52.550
based on a in one

NOTE Confidence: 0.9750722

00:10:52.550 --> 00:10:54.010
study, based on a positivity

NOTE Confidence: 0.98566717

00:10:54.390 --> 00:10:56.309
of, greater than seventy five

NOTE Confidence: 0.98566717

00:10:56.309 --> 00:10:57.510
percent two plus or three

NOTE Confidence: 0.98566717

00:10:57.510 --> 00:10:58.250
plus expression,

NOTE Confidence: 0.9817666

00:10:58.870 --> 00:11:00.230
we find positivity in about

NOTE Confidence: 0.9817666

00:11:00.230 --> 00:11:01.910
thirty eight percent of, of

NOTE Confidence: 0.9817666

00:11:01.910 --> 00:11:03.029
cancers. And you can kind

NOTE Confidence: 0.9817666

00:11:03.029 --> 00:11:04.630
of see that, this high,

NOTE Confidence: 0.9817666

00:11:04.870 --> 00:11:05.370
positivity

NOTE Confidence: 0.9967383

00:11:06.285 --> 00:11:06.785
here.

NOTE Confidence: 0.9433094

00:11:08.204 --> 00:11:08.684
And,

NOTE Confidence: 0.9804434

00:11:09.245 --> 00:11:10.764
this was the cutoff that

NOTE Confidence: 0.9804434

00:11:10.764 --> 00:11:11.884
was used for the study

NOTE Confidence: 0.9804434

00:11:11.884 --> 00:11:13.345
to look at, zolventuximab,

NOTE Confidence: 0.98754096

00:11:15.485 --> 00:11:16.605
which is the the main

NOTE Confidence: 0.98754096

00:11:16.605 --> 00:11:18.545
antibody that's targeting this pathway.

NOTE Confidence: 0.98754096

00:11:18.764 --> 00:11:20.524
But there are other novel,

NOTE Confidence: 0.98754096

00:11:20.764 --> 00:11:21.264
antibodies

NOTE Confidence: 0.84343433

00:11:21.565 --> 00:11:21.870
that,

NOTE Confidence: 0.6674051

00:11:24.309 --> 00:11:24.850
and antibody,

NOTE Confidence: 0.99855953

00:11:25.309 --> 00:11:27.410
drug conjugates that could potentially

NOTE Confidence: 0.99855953

00:11:27.550 --> 00:11:29.809
be useful to target lower

NOTE Confidence: 0.99855953

00:11:29.870 --> 00:11:30.850
level expression

NOTE Confidence: 0.9992181

00:11:31.390 --> 00:11:32.850
of this particular biomarker.

NOTE Confidence: 0.98577404

00:11:33.150 --> 00:11:34.750
So if you include those,

NOTE Confidence: 0.98577404

00:11:34.750 --> 00:11:35.870
then you're you're adding a

NOTE Confidence: 0.98577404

00:11:35.870 --> 00:11:36.405
lot more,

NOTE Confidence: 0.99892867

00:11:37.045 --> 00:11:38.965
patients to the possibility of

NOTE Confidence: 0.99892867

00:11:38.965 --> 00:11:40.265
getting targeted treatment.

NOTE Confidence: 0.997714

00:11:40.645 --> 00:11:41.525
And I just I have

NOTE Confidence: 0.997714

00:11:41.525 --> 00:11:42.405
a summary here of all

NOTE Confidence: 0.997714

00:11:42.405 --> 00:11:43.525
the phase two and three

NOTE Confidence: 0.997714

00:11:43.525 --> 00:11:45.125
clinical trials from one of

NOTE Confidence: 0.997714

00:11:45.125 --> 00:11:46.105
the recent reviews

NOTE Confidence: 0.9983155

00:11:46.485 --> 00:11:47.845
for anybody who's interested in

NOTE Confidence: 0.9983155

00:11:47.845 --> 00:11:48.585
more detail.

NOTE Confidence: 0.9774768

00:11:49.410 --> 00:11:50.209
And so what do we

NOTE Confidence: 0.9774768

00:11:50.209 --> 00:11:51.570
do at Yale for claudine

NOTE Confidence: 0.9774768

00:11:51.570 --> 00:11:52.790
eighteen point two?

NOTE Confidence: 0.9620447

00:11:53.410 --> 00:11:54.690
So we, again, use the

NOTE Confidence: 0.9620447

00:11:54.690 --> 00:11:55.670
FDA approved,

NOTE Confidence: 0.9471323

00:11:56.690 --> 00:11:57.190
assay,

NOTE Confidence: 0.9799203

00:11:57.730 --> 00:11:59.170
which is the forty three

NOTE Confidence: 0.9799203

00:11:59.170 --> 00:12:00.709
dash fourteen a,

NOTE Confidence: 0.99492157

00:12:01.490 --> 00:12:01.990
antibody.

NOTE Confidence: 0.88842785

00:12:03.165 --> 00:12:03.665
And,

NOTE Confidence: 0.9805016

00:12:04.605 --> 00:12:06.365
we, when we report the

NOTE Confidence: 0.9805016

00:12:06.365 --> 00:12:08.205
results of our claudan eighteen

NOTE Confidence: 0.9805016

00:12:08.205 --> 00:12:10.545
staining, we report it in

NOTE Confidence: 0.6107034

00:12:11.165 --> 00:12:11.665
categories.

NOTE Confidence: 0.9993973

00:12:12.205 --> 00:12:13.645
So greater than seventy five

NOTE Confidence: 0.9993973

00:12:13.645 --> 00:12:14.145
percent

NOTE Confidence: 0.9842363

00:12:15.660 --> 00:12:17.760
positivity, fifty to seventy five,

NOTE Confidence: 0.9842363

00:12:18.059 --> 00:12:19.500
twenty to forty nine, one

NOTE Confidence: 0.9842363

00:12:19.500 --> 00:12:21.040
to nineteen, and zero percent.

NOTE Confidence: 0.9842363

00:12:21.340 --> 00:12:23.260
And that's because we wanna

NOTE Confidence: 0.9842363

00:12:23.260 --> 00:12:24.960
be ready for those newer,

NOTE Confidence: 0.9973297

00:12:26.220 --> 00:12:27.600
antibody drug conjugates

NOTE Confidence: 0.9935033

00:12:28.495 --> 00:12:30.675
and bispecific antibodies to see,

NOTE Confidence: 0.9994837

00:12:31.375 --> 00:12:33.395
if these patients would benefit

NOTE Confidence: 0.9994837

00:12:33.455 --> 00:12:35.235
from those in the future.

NOTE Confidence: 0.9801394

00:12:35.775 --> 00:12:36.735
And, again, you can kind

NOTE Confidence: 0.9801394

00:12:36.735 --> 00:12:37.875
of see what the spectrum

NOTE Confidence: 0.9801394

00:12:38.095 --> 00:12:39.475
of staining is.

NOTE Confidence: 0.99938077

00:12:40.015 --> 00:12:40.835
It's a relatively

NOTE Confidence: 0.9444163

00:12:42.940 --> 00:12:43.900
easy antibody,

NOTE Confidence: 0.9739626

00:12:44.380 --> 00:12:45.740
to read. And then we

NOTE Confidence: 0.9739626

00:12:45.740 --> 00:12:46.860
always look for our normal

NOTE Confidence: 0.9739626

00:12:46.860 --> 00:12:48.079
controls in the background,

NOTE Confidence: 0.99275035

00:12:48.459 --> 00:12:48.959
mucosa.

NOTE Confidence: 0.99023485

00:12:49.660 --> 00:12:51.500
Okay. So that's the basically,

NOTE Confidence: 0.99023485

00:12:51.500 --> 00:12:52.540
the end of my talk.

NOTE Confidence: 0.99023485

00:12:52.540 --> 00:12:54.059
I've described all four of

NOTE Confidence: 0.99023485

00:12:54.059 --> 00:12:54.880
these biomarkers

NOTE Confidence: 0.98752797

00:12:55.904 --> 00:12:56.345
and,

NOTE Confidence: 0.99752516

00:12:56.785 --> 00:12:57.845
what they're targeting

NOTE Confidence: 0.9883469

00:12:58.225 --> 00:13:00.084
and how we assess them.

NOTE Confidence: 0.9564303

00:13:00.704 --> 00:13:01.204
And,

NOTE Confidence: 0.93857574

00:13:02.144 --> 00:13:03.345
this is already out of

NOTE Confidence: 0.93857574

00:13:03.345 --> 00:13:05.105
date because we do have

NOTE Confidence: 0.93857574

00:13:05.105 --> 00:13:07.505
a emerging predictive biomarker, FGF

NOTE Confidence: 0.93857574

00:13:07.505 --> 00:13:08.800
r two b that's coming

NOTE Confidence: 0.93857574

00:13:08.800 --> 00:13:09.300
up.

NOTE Confidence: 0.97064817

00:13:10.080 --> 00:13:12.399
And, we are getting ready

NOTE Confidence: 0.97064817

00:13:12.399 --> 00:13:14.080
to have that IHC testing

NOTE Confidence: 0.97064817

00:13:14.080 --> 00:13:16.080
method, brought on board for

NOTE Confidence: 0.97064817

00:13:16.080 --> 00:13:17.120
us. So this is just

NOTE Confidence: 0.97064817

00:13:17.120 --> 00:13:17.860
stay tuned

NOTE Confidence: 0.99927604

00:13:18.399 --> 00:13:19.940
about this in the future.

NOTE Confidence: 0.9674623

00:13:20.554 --> 00:13:21.595
And so here I have

NOTE Confidence: 0.9674623

00:13:21.595 --> 00:13:23.355
a summary table for anyone

NOTE Confidence: 0.9674623

00:13:23.355 --> 00:13:24.175
who's interested.

NOTE Confidence: 0.94646955

00:13:25.035 --> 00:13:25.535
So,

NOTE Confidence: 0.9855321

00:13:25.995 --> 00:13:28.154
again, we have our four

NOTE Confidence: 0.9855321

00:13:28.154 --> 00:13:29.675
IHC biomarkers that we are

NOTE Confidence: 0.9855321

00:13:29.675 --> 00:13:31.774
performing as a reflex workflow

NOTE Confidence: 0.9855321

00:13:32.074 --> 00:13:33.595
so that we're providing this,

NOTE Confidence: 0.99979657

00:13:33.995 --> 00:13:34.495
information

NOTE Confidence: 0.99909633

00:13:34.954 --> 00:13:35.694
at diagnosis

NOTE Confidence: 0.965336

00:13:36.800 --> 00:13:37.300
and,

NOTE Confidence: 0.97433156

00:13:38.720 --> 00:13:39.920
for, you know, the the

NOTE Confidence: 0.97433156

00:13:39.920 --> 00:13:40.800
various, uses,

NOTE Confidence: 0.9579641

00:13:42.880 --> 00:13:44.959
clinically and just, you know,

NOTE Confidence: 0.9579641

00:13:44.959 --> 00:13:46.559
again, just the summary chart

NOTE Confidence: 0.9579641

00:13:46.559 --> 00:13:47.600
of all the information I

NOTE Confidence: 0.9579641

00:13:47.600 --> 00:13:49.360
talked about today. And I'll

NOTE Confidence: 0.9579641

00:13:49.360 --> 00:13:51.184
stop there, and I'm happy

NOTE Confidence: 0.9579641

00:13:51.184 --> 00:13:52.225
to take any questions. And

NOTE Confidence: 0.9579641

00:13:52.225 --> 00:13:53.425
I I apologize if I

NOTE Confidence: 0.9579641

00:13:53.425 --> 00:13:54.645
went a little too long.

NOTE Confidence: 0.87889457

00:13:55.985 --> 00:13:57.025
Let's see. Thanks. That was

NOTE Confidence: 0.87889457

00:13:57.025 --> 00:13:58.304
good. Doctor Gibson, that was

NOTE Confidence: 0.87889457

00:13:58.304 --> 00:13:59.905
a great talk. I can,

NOTE Confidence: 0.87889457

00:14:00.304 --> 00:14:01.445
may I encourage

NOTE Confidence: 0.8863809

00:14:02.304 --> 00:14:03.825
the viewers, listeners to,

NOTE Confidence: 0.97527695

00:14:04.580 --> 00:14:05.460
put in any questions that

NOTE Confidence: 0.97527695

00:14:05.460 --> 00:14:06.500
you have into the chat

NOTE Confidence: 0.97527695

00:14:06.500 --> 00:14:07.460
or into the q and

NOTE Confidence: 0.97527695

00:14:07.460 --> 00:14:08.740
a box, and we'll try

NOTE Confidence: 0.97527695

00:14:08.740 --> 00:14:09.640
and do them,

NOTE Confidence: 0.960079

00:14:10.340 --> 00:14:11.620
either now or at the

NOTE Confidence: 0.960079

00:14:11.620 --> 00:14:13.059
end of the the session

NOTE Confidence: 0.960079

00:14:13.059 --> 00:14:14.179
when after all after all

NOTE Confidence: 0.960079

00:14:14.179 --> 00:14:15.480
four of us speak because

NOTE Confidence: 0.960079

00:14:15.540 --> 00:14:16.260
I think it'll be quite

NOTE Confidence: 0.960079

00:14:16.260 --> 00:14:17.480
helpful to have a multidisciplinary

NOTE Confidence: 0.99984324

00:14:18.020 --> 00:14:18.520
discussion

NOTE Confidence: 0.99645317

00:14:18.900 --> 00:14:19.620
at the end of all

NOTE Confidence: 0.99645317

00:14:19.620 --> 00:14:20.280
the chats.

NOTE Confidence: 0.97021353

00:14:21.755 --> 00:14:23.194
If there are no emerging

NOTE Confidence: 0.97021353

00:14:23.194 --> 00:14:24.555
questions, maybe we'll move on

NOTE Confidence: 0.97021353

00:14:24.555 --> 00:14:26.795
to, doctor Baufa, who's gonna

NOTE Confidence: 0.97021353

00:14:26.795 --> 00:14:27.755
give us an update from

NOTE Confidence: 0.97021353

00:14:27.755 --> 00:14:28.975
the surgical perspective.

NOTE Confidence: 0.9673576

00:14:38.279 --> 00:14:39.560
Hi there. Thank you very

NOTE Confidence: 0.9673576

00:14:39.560 --> 00:14:41.240
much. Dan Boffa. I'm one

NOTE Confidence: 0.9673576

00:14:41.240 --> 00:14:41.560
of the,

NOTE Confidence: 0.97818285

00:14:42.279 --> 00:14:43.420
thoracic surgeons,

NOTE Confidence: 0.96657246

00:14:43.959 --> 00:14:45.399
here at Yale. And I'm

NOTE Confidence: 0.96657246

00:14:45.399 --> 00:14:46.379
just gonna talk

NOTE Confidence: 0.985286

00:14:47.445 --> 00:14:49.525
briefly about, a couple of

NOTE Confidence: 0.985286

00:14:49.525 --> 00:14:51.385
aspects of the surgical management

NOTE Confidence: 0.985286

00:14:51.525 --> 00:14:52.185
of esophageal

NOTE Confidence: 0.999208

00:14:52.485 --> 00:14:52.985
cancer.

NOTE Confidence: 0.73267674

00:14:54.685 --> 00:14:55.185
So,

NOTE Confidence: 0.9128021

00:14:57.205 --> 00:14:58.805
may I have a couple

NOTE Confidence: 0.9128021

00:14:58.805 --> 00:14:59.545
of disclosures?

NOTE Confidence: 0.93017465

00:15:00.730 --> 00:15:02.250
This is what people think

NOTE Confidence: 0.93017465

00:15:02.250 --> 00:15:02.330
about,

NOTE Confidence: 0.863695

00:15:03.450 --> 00:15:05.470
when we mention an esophageectomy

NOTE Confidence: 0.9167757

00:15:05.850 --> 00:15:07.610
for esophageal cancer, that it's

NOTE Confidence: 0.9167757

00:15:07.610 --> 00:15:09.630
a extremely dangerous thing,

NOTE Confidence: 0.97148126

00:15:10.170 --> 00:15:11.790
to deal with an extremely

NOTE Confidence: 0.97148126

00:15:11.850 --> 00:15:12.830
dangerous problem.

NOTE Confidence: 0.9052628

00:15:13.505 --> 00:15:14.005
And,

NOTE Confidence: 0.9867225

00:15:14.385 --> 00:15:15.745
hopefully, I can convince you

NOTE Confidence: 0.9867225

00:15:15.745 --> 00:15:16.865
at at some level that

NOTE Confidence: 0.9867225

00:15:16.865 --> 00:15:19.205
it's become infinitely safer,

NOTE Confidence: 0.9597896

00:15:20.065 --> 00:15:20.565
and,

NOTE Confidence: 0.99051774

00:15:21.025 --> 00:15:21.685
the recovery

NOTE Confidence: 0.6904079

00:15:22.705 --> 00:15:23.205
is,

NOTE Confidence: 0.97373

00:15:23.825 --> 00:15:24.945
is much different now with

NOTE Confidence: 0.97373

00:15:24.945 --> 00:15:25.925
minimally invasive,

NOTE Confidence: 0.9626663

00:15:26.385 --> 00:15:26.885
approaches.

NOTE Confidence: 0.9872117

00:15:27.510 --> 00:15:28.390
But I do think it's

NOTE Confidence: 0.9872117

00:15:28.390 --> 00:15:29.610
an important question.

NOTE Confidence: 0.9987955

00:15:29.910 --> 00:15:30.410
And

NOTE Confidence: 0.95505303

00:15:30.950 --> 00:15:31.450
and

NOTE Confidence: 0.9830635

00:15:31.990 --> 00:15:32.950
do we need to do

NOTE Confidence: 0.9830635

00:15:32.950 --> 00:15:33.690
an esophagectomy

NOTE Confidence: 0.99002016

00:15:34.710 --> 00:15:35.990
in everyone? And I think

NOTE Confidence: 0.99002016

00:15:35.990 --> 00:15:36.950
that some of the most

NOTE Confidence: 0.99002016

00:15:36.950 --> 00:15:37.450
exciting,

NOTE Confidence: 0.9997527

00:15:38.950 --> 00:15:40.710
trial data that's been coming

NOTE Confidence: 0.9997527

00:15:40.710 --> 00:15:41.210
through

NOTE Confidence: 0.99137866

00:15:41.665 --> 00:15:43.045
is looking at things,

NOTE Confidence: 0.93771243

00:15:43.505 --> 00:15:44.725
that maybe we,

NOTE Confidence: 0.99976397

00:15:45.105 --> 00:15:46.785
can be more selective in

NOTE Confidence: 0.99976397

00:15:46.785 --> 00:15:47.525
how we

NOTE Confidence: 0.9618409

00:15:48.065 --> 00:15:49.525
apply some of the traditional

NOTE Confidence: 0.9618409

00:15:49.585 --> 00:15:51.665
treatments as well as, some

NOTE Confidence: 0.9618409

00:15:51.665 --> 00:15:53.185
of the the newer treatments.

NOTE Confidence: 0.9618409

00:15:53.185 --> 00:15:53.685
So

NOTE Confidence: 0.96547395

00:15:55.020 --> 00:15:56.700
this I'm gonna focus on

NOTE Confidence: 0.96547395

00:15:56.700 --> 00:15:58.720
the the Saino trial, which

NOTE Confidence: 0.96547395

00:15:58.940 --> 00:16:00.300
is a phase three,

NOTE Confidence: 0.9672387

00:16:00.700 --> 00:16:01.200
trial,

NOTE Confidence: 0.917499

00:16:01.900 --> 00:16:03.120
that looked at,

NOTE Confidence: 0.9228478

00:16:04.779 --> 00:16:05.840
selecting people

NOTE Confidence: 0.9995327

00:16:06.315 --> 00:16:07.695
to not go

NOTE Confidence: 0.9581394

00:16:08.075 --> 00:16:10.095
on to surgery after receiving,

NOTE Confidence: 0.8693345

00:16:11.275 --> 00:16:13.855
the cross regimen of induction,

NOTE Confidence: 0.9559846

00:16:14.395 --> 00:16:14.895
chemoradiation.

NOTE Confidence: 0.9497531

00:16:16.635 --> 00:16:17.935
Before that, though,

NOTE Confidence: 0.9891681

00:16:18.555 --> 00:16:19.995
you have to know that

NOTE Confidence: 0.9891681

00:16:19.995 --> 00:16:21.900
the person has experienced a

NOTE Confidence: 0.9891681

00:16:21.900 --> 00:16:24.160
complete clinical response. And so

NOTE Confidence: 0.9700852

00:16:24.620 --> 00:16:25.820
there there was a trial

NOTE Confidence: 0.9700852

00:16:25.820 --> 00:16:27.020
before the trial, which is

NOTE Confidence: 0.9700852

00:16:27.020 --> 00:16:29.280
the presaino trial, which was

NOTE Confidence: 0.9586981

00:16:29.740 --> 00:16:31.440
looking at, could you tell

NOTE Confidence: 0.99963

00:16:31.820 --> 00:16:33.500
if people had been cleared

NOTE Confidence: 0.99963

00:16:33.500 --> 00:16:34.480
of their disease

NOTE Confidence: 0.95273966

00:16:37.425 --> 00:16:38.865
after receiving CROS. Because if

NOTE Confidence: 0.95273966

00:16:38.865 --> 00:16:40.225
you couldn't do that, then

NOTE Confidence: 0.95273966

00:16:40.225 --> 00:16:40.705
there's,

NOTE Confidence: 0.99245685

00:16:41.185 --> 00:16:42.325
no point in,

NOTE Confidence: 0.9613543

00:16:42.865 --> 00:16:44.705
the trial, which is taking

NOTE Confidence: 0.9613543

00:16:44.705 --> 00:16:45.985
people who appear to have

NOTE Confidence: 0.9613543

00:16:45.985 --> 00:16:47.365
been cleared of their disease

NOTE Confidence: 0.736292

00:16:47.745 --> 00:16:48.245
and,

NOTE Confidence: 0.99941146

00:16:49.040 --> 00:16:49.540
selectively

NOTE Confidence: 0.9775073

00:16:49.920 --> 00:16:51.519
watching them to see if

NOTE Confidence: 0.9775073

00:16:51.519 --> 00:16:52.800
the the cancer came back

NOTE Confidence: 0.9775073

00:16:52.800 --> 00:16:54.260
and deferring esophagectomy

NOTE Confidence: 0.9874797

00:16:54.720 --> 00:16:55.920
to only those people where

NOTE Confidence: 0.9874797

00:16:55.920 --> 00:16:57.040
the cancer came back. And

NOTE Confidence: 0.9874797

00:16:57.040 --> 00:16:58.800
so this was the trial

NOTE Confidence: 0.9874797

00:16:58.800 --> 00:17:00.339
to determine, could you

NOTE Confidence: 0.98614573

00:17:00.720 --> 00:17:02.639
detect people that were free

NOTE Confidence: 0.98614573

00:17:02.639 --> 00:17:04.419
of residual disease? This was

NOTE Confidence: 0.98614573

00:17:04.615 --> 00:17:06.375
done in the Netherlands. Again,

NOTE Confidence: 0.98614573

00:17:06.375 --> 00:17:07.575
it was after the CROS

NOTE Confidence: 0.98614573

00:17:07.575 --> 00:17:08.075
regimen.

NOTE Confidence: 0.6828835

00:17:08.934 --> 00:17:09.434
The

NOTE Confidence: 0.9768703

00:17:12.294 --> 00:17:12.794
the

NOTE Confidence: 0.94751906

00:17:13.095 --> 00:17:14.534
four to six weeks after

NOTE Confidence: 0.94751906

00:17:14.534 --> 00:17:15.734
the completion of the chemo

NOTE Confidence: 0.94751906

00:17:15.734 --> 00:17:17.355
radiation, they underwent an endoscopy.

NOTE Confidence: 0.9435304

00:17:18.270 --> 00:17:18.770
And,

NOTE Confidence: 0.81838346

00:17:19.550 --> 00:17:19.950
if,

NOTE Confidence: 0.9926818

00:17:20.670 --> 00:17:22.670
they, was there was viable

NOTE Confidence: 0.9926818

00:17:22.670 --> 00:17:23.170
cancer,

NOTE Confidence: 0.9794442

00:17:23.630 --> 00:17:24.910
they did a PET scan

NOTE Confidence: 0.9794442

00:17:24.910 --> 00:17:25.970
and an esophagectomy

NOTE Confidence: 0.9995332

00:17:26.510 --> 00:17:27.250
right away.

NOTE Confidence: 0.9990962

00:17:27.550 --> 00:17:28.670
If they didn't see vital

NOTE Confidence: 0.9990962

00:17:28.990 --> 00:17:30.430
any viable cancer, they did

NOTE Confidence: 0.9990962

00:17:30.430 --> 00:17:31.410
a second endoscopy,

NOTE Confidence: 0.95693487

00:17:32.984 --> 00:17:34.665
an ultrasound, a PET scan,

NOTE Confidence: 0.95693487

00:17:34.665 --> 00:17:36.744
and then everybody got an

NOTE Confidence: 0.95693487

00:17:36.744 --> 00:17:37.244
esophageectomy,

NOTE Confidence: 0.94908273

00:17:38.585 --> 00:17:41.165
after the, the second evaluation.

NOTE Confidence: 0.92147225

00:17:42.905 --> 00:17:44.185
So there were about two

NOTE Confidence: 0.92147225

00:17:44.185 --> 00:17:45.625
hundred and twenty patients. This

NOTE Confidence: 0.92147225

00:17:45.625 --> 00:17:46.285
was done

NOTE Confidence: 0.98908424

00:17:47.500 --> 00:17:49.020
a few years ago. They

NOTE Confidence: 0.98908424

00:17:49.020 --> 00:17:50.240
were mostly adenocarcinomas,

NOTE Confidence: 0.9996403

00:17:51.340 --> 00:17:52.720
and they wanted to see

NOTE Confidence: 0.9930218

00:17:53.180 --> 00:17:54.619
that of the people who

NOTE Confidence: 0.9930218

00:17:54.619 --> 00:17:56.960
had cancer still in them,

NOTE Confidence: 0.996772

00:17:57.740 --> 00:17:58.940
what was the proportion of

NOTE Confidence: 0.996772

00:17:58.940 --> 00:18:01.280
them that had a negative

NOTE Confidence: 0.8603374

00:18:02.785 --> 00:18:03.845
clinical assessment?

NOTE Confidence: 0.9945476

00:18:04.305 --> 00:18:05.825
And they called those false

NOTE Confidence: 0.9945476

00:18:05.825 --> 00:18:06.325
negatives.

NOTE Confidence: 0.9429239

00:18:07.585 --> 00:18:08.625
And so they started by

NOTE Confidence: 0.9429239

00:18:08.625 --> 00:18:09.765
just doing biopsies

NOTE Confidence: 0.9582951

00:18:10.065 --> 00:18:11.825
the way they routinely do

NOTE Confidence: 0.9582951

00:18:11.825 --> 00:18:12.325
biopsies.

NOTE Confidence: 0.8797555

00:18:13.025 --> 00:18:13.925
And they,

NOTE Confidence: 0.9416097

00:18:14.785 --> 00:18:15.905
they had a a false

NOTE Confidence: 0.9416097

00:18:15.905 --> 00:18:16.805
negative rate

NOTE Confidence: 0.97287697

00:18:17.850 --> 00:18:19.770
of about thirty percent. So

NOTE Confidence: 0.97287697

00:18:19.770 --> 00:18:20.890
then they started doing a

NOTE Confidence: 0.97287697

00:18:20.890 --> 00:18:22.250
byte on byte, which just

NOTE Confidence: 0.97287697

00:18:22.250 --> 00:18:23.310
basically means,

NOTE Confidence: 0.98930824

00:18:24.170 --> 00:18:25.690
that they took a byte

NOTE Confidence: 0.98930824

00:18:25.690 --> 00:18:27.050
and then went back to

NOTE Confidence: 0.98930824

00:18:27.050 --> 00:18:28.650
the same area and bit

NOTE Confidence: 0.98930824

00:18:28.650 --> 00:18:30.250
in the same area again,

NOTE Confidence: 0.98930824

00:18:30.250 --> 00:18:31.450
which gets a little bit

NOTE Confidence: 0.98930824

00:18:31.450 --> 00:18:31.950
deeper.

NOTE Confidence: 0.9517106

00:18:33.225 --> 00:18:35.225
Using this, they found, the

NOTE Confidence: 0.9517106

00:18:35.225 --> 00:18:37.005
false negative rate, again,

NOTE Confidence: 0.98253036

00:18:37.305 --> 00:18:40.025
meaning negative results in people

NOTE Confidence: 0.98253036

00:18:40.025 --> 00:18:41.625
who still had at least

NOTE Confidence: 0.98253036

00:18:41.625 --> 00:18:42.445
ten percent,

NOTE Confidence: 0.866903

00:18:43.065 --> 00:18:45.325
of their residual cancer.

NOTE Confidence: 0.9736784

00:18:46.169 --> 00:18:47.609
So it improved from thirty

NOTE Confidence: 0.9736784

00:18:47.609 --> 00:18:49.369
percent to seventeen percent. And

NOTE Confidence: 0.9736784

00:18:49.369 --> 00:18:50.970
when they added FNA of

NOTE Confidence: 0.9736784

00:18:50.970 --> 00:18:52.250
nodes that were bigger than

NOTE Confidence: 0.9736784

00:18:52.250 --> 00:18:52.990
five millimeters,

NOTE Confidence: 0.99782497

00:18:53.369 --> 00:18:54.409
it went down to ten

NOTE Confidence: 0.99782497

00:18:54.409 --> 00:18:55.389
percent. So

NOTE Confidence: 0.9994567

00:18:55.690 --> 00:18:57.230
ten percent of the patients

NOTE Confidence: 0.9994567

00:18:57.289 --> 00:18:58.109
who had

NOTE Confidence: 0.99901325

00:18:59.635 --> 00:19:00.695
residual cancer,

NOTE Confidence: 0.9628959

00:19:01.395 --> 00:19:02.755
which they defined as greater

NOTE Confidence: 0.9628959

00:19:02.755 --> 00:19:04.535
than ten percent residual cancer,

NOTE Confidence: 0.99936503

00:19:04.994 --> 00:19:06.455
had a false negative.

NOTE Confidence: 0.93395007

00:19:07.395 --> 00:19:08.515
And so this is a

NOTE Confidence: 0.93395007

00:19:08.515 --> 00:19:10.035
table by group and the

NOTE Confidence: 0.93395007

00:19:10.035 --> 00:19:10.535
TRG,

NOTE Confidence: 0.98405385

00:19:11.970 --> 00:19:13.170
at the top here, this

NOTE Confidence: 0.98405385

00:19:13.170 --> 00:19:15.250
is their different categories of

NOTE Confidence: 0.98405385

00:19:15.250 --> 00:19:17.250
residual disease. And so if

NOTE Confidence: 0.98405385

00:19:17.250 --> 00:19:18.770
you were a TGR one,

NOTE Confidence: 0.98405385

00:19:18.770 --> 00:19:20.150
you had a complete pathologic

NOTE Confidence: 0.98405385

00:19:20.369 --> 00:19:20.869
response,

NOTE Confidence: 0.98552895

00:19:21.970 --> 00:19:23.330
or you had one to

NOTE Confidence: 0.98552895

00:19:23.330 --> 00:19:25.430
ten percent viable cancer,

NOTE Confidence: 0.9469524

00:19:27.715 --> 00:19:28.675
or greater than ten percent

NOTE Confidence: 0.9469524

00:19:28.675 --> 00:19:29.895
but less than fifty,

NOTE Confidence: 0.98946786

00:19:30.275 --> 00:19:31.715
or greater than fifty percent.

NOTE Confidence: 0.98946786

00:19:31.715 --> 00:19:33.234
These are the categories that

NOTE Confidence: 0.98946786

00:19:33.234 --> 00:19:33.734
they

NOTE Confidence: 0.9810694

00:19:34.035 --> 00:19:35.734
code their viable cancer.

NOTE Confidence: 0.9843735

00:19:36.275 --> 00:19:37.635
And this is what the

NOTE Confidence: 0.9843735

00:19:37.635 --> 00:19:38.915
study was designed to look

NOTE Confidence: 0.9843735

00:19:38.915 --> 00:19:40.295
at, just these patients

NOTE Confidence: 0.9835679

00:19:40.940 --> 00:19:42.540
who had more than ten

NOTE Confidence: 0.9835679

00:19:42.540 --> 00:19:44.080
percent viable cancer,

NOTE Confidence: 0.9894395

00:19:44.540 --> 00:19:45.680
and they found,

NOTE Confidence: 0.99863625

00:19:46.220 --> 00:19:47.100
that there was a ten

NOTE Confidence: 0.99863625

00:19:47.100 --> 00:19:48.640
percent false negative rate.

NOTE Confidence: 0.982432

00:19:49.580 --> 00:19:50.619
But they didn't really look

NOTE Confidence: 0.982432

00:19:50.619 --> 00:19:51.980
at the people with one

NOTE Confidence: 0.982432

00:19:51.980 --> 00:19:53.900
to ten percent residual cancer.

NOTE Confidence: 0.982432

00:19:53.900 --> 00:19:55.435
And I would argue that

NOTE Confidence: 0.982432

00:19:55.435 --> 00:19:57.695
patients probably care about that,

NOTE Confidence: 0.9875152

00:19:58.234 --> 00:19:59.595
that that if you're really

NOTE Confidence: 0.9875152

00:19:59.595 --> 00:20:01.055
looking to see who's been

NOTE Confidence: 0.9875152

00:20:01.115 --> 00:20:03.035
rendered disease free, you'd wanna

NOTE Confidence: 0.9875152

00:20:03.035 --> 00:20:04.734
know any living disease.

NOTE Confidence: 0.99866134

00:20:05.515 --> 00:20:07.275
But what's funny about this

NOTE Confidence: 0.99866134

00:20:07.275 --> 00:20:07.775
is

NOTE Confidence: 0.98535633

00:20:09.140 --> 00:20:10.260
this the way this was

NOTE Confidence: 0.98535633

00:20:10.260 --> 00:20:11.380
set up was to say,

NOTE Confidence: 0.98535633

00:20:11.380 --> 00:20:12.580
how well does the test

NOTE Confidence: 0.98535633

00:20:12.580 --> 00:20:13.080
perform?

NOTE Confidence: 0.9948339

00:20:13.619 --> 00:20:14.519
So given

NOTE Confidence: 0.9949763

00:20:15.460 --> 00:20:16.600
residual cancer,

NOTE Confidence: 0.9990985

00:20:16.980 --> 00:20:18.659
is the test coming up

NOTE Confidence: 0.9990985

00:20:18.659 --> 00:20:19.940
with a positive or negative

NOTE Confidence: 0.9990985

00:20:19.940 --> 00:20:21.619
result? Well, patients don't think

NOTE Confidence: 0.9990985

00:20:21.619 --> 00:20:22.820
that way. They don't care

NOTE Confidence: 0.9990985

00:20:22.820 --> 00:20:23.320
about

NOTE Confidence: 0.9921697

00:20:24.175 --> 00:20:25.695
scenarios and how the test

NOTE Confidence: 0.9921697

00:20:25.695 --> 00:20:27.215
performs. They wanna know about

NOTE Confidence: 0.9921697

00:20:27.215 --> 00:20:28.494
test results and what does

NOTE Confidence: 0.9921697

00:20:28.494 --> 00:20:29.155
it mean.

NOTE Confidence: 0.99100924

00:20:29.695 --> 00:20:31.055
So if a test says

NOTE Confidence: 0.99100924

00:20:31.055 --> 00:20:32.575
no cancer, what is the

NOTE Confidence: 0.99100924

00:20:32.575 --> 00:20:34.335
chance that you actually have

NOTE Confidence: 0.99100924

00:20:34.335 --> 00:20:35.955
cancer? That's the false negative

NOTE Confidence: 0.99100924

00:20:36.015 --> 00:20:36.390
rate,

NOTE Confidence: 0.99688894

00:20:37.270 --> 00:20:39.590
that really matters most to

NOTE Confidence: 0.99688894

00:20:39.590 --> 00:20:40.950
patients, and that points to

NOTE Confidence: 0.99688894

00:20:40.950 --> 00:20:42.630
negative and positive predictive value.

NOTE Confidence: 0.99688894

00:20:42.630 --> 00:20:43.910
And so when you look

NOTE Confidence: 0.99688894

00:20:43.910 --> 00:20:45.030
at all the people who

NOTE Confidence: 0.99688894

00:20:45.030 --> 00:20:46.970
had a negative test result,

NOTE Confidence: 0.9660356

00:20:47.590 --> 00:20:48.869
and granted that this was

NOTE Confidence: 0.9660356

00:20:48.869 --> 00:20:50.230
published saying there's a ten

NOTE Confidence: 0.9660356

00:20:50.230 --> 00:20:51.855
percent false negative rate to

NOTE Confidence: 0.9660356

00:20:51.855 --> 00:20:52.595
this presano

NOTE Confidence: 0.9909307

00:20:53.215 --> 00:20:54.415
trial. But if you actually

NOTE Confidence: 0.9909307

00:20:54.415 --> 00:20:55.934
looked at everybody who had

NOTE Confidence: 0.9909307

00:20:55.934 --> 00:20:57.395
a negative test result,

NOTE Confidence: 0.9411297

00:20:57.855 --> 00:20:58.975
there were twenty nine,

NOTE Confidence: 0.97226745

00:20:59.375 --> 00:21:00.515
negative test results.

NOTE Confidence: 0.972919

00:21:00.895 --> 00:21:02.015
They the patient still had

NOTE Confidence: 0.972919

00:21:02.015 --> 00:21:03.375
cancer fifty five percent of

NOTE Confidence: 0.972919

00:21:03.375 --> 00:21:04.515
the time. And so

NOTE Confidence: 0.9784608

00:21:04.840 --> 00:21:06.280
that's just an important number

NOTE Confidence: 0.9784608

00:21:06.280 --> 00:21:07.160
to keep in the back

NOTE Confidence: 0.9784608

00:21:07.160 --> 00:21:08.200
of your head that a

NOTE Confidence: 0.9784608

00:21:08.200 --> 00:21:08.700
negative,

NOTE Confidence: 0.8879463

00:21:09.480 --> 00:21:10.860
Sano level evaluation,

NOTE Confidence: 0.9849693

00:21:12.680 --> 00:21:14.680
there's viable cancer half the

NOTE Confidence: 0.9849693

00:21:14.680 --> 00:21:15.180
time.

NOTE Confidence: 0.9532859

00:21:16.760 --> 00:21:18.119
So now to talk about

NOTE Confidence: 0.9532859

00:21:18.119 --> 00:21:19.180
the Sano trial.

NOTE Confidence: 0.9900482

00:21:19.725 --> 00:21:21.505
So, this is a really

NOTE Confidence: 0.80009514

00:21:22.125 --> 00:21:22.945
nice trial

NOTE Confidence: 0.809954

00:21:23.244 --> 00:21:23.744
done,

NOTE Confidence: 0.9017904

00:21:24.205 --> 00:21:25.265
again, in the Netherlands.

NOTE Confidence: 0.9989228

00:21:25.885 --> 00:21:27.265
Twelve high volume

NOTE Confidence: 0.95763826

00:21:27.804 --> 00:21:29.085
centers, and it was it's

NOTE Confidence: 0.95763826

00:21:29.085 --> 00:21:30.225
a recent trial,

NOTE Confidence: 0.8810838

00:21:31.085 --> 00:21:32.304
similar to presano,

NOTE Confidence: 0.9504605

00:21:33.690 --> 00:21:35.690
mostly adeno, and about twenty

NOTE Confidence: 0.9504605

00:21:35.690 --> 00:21:37.690
five percent squamous. And, again,

NOTE Confidence: 0.9504605

00:21:37.690 --> 00:21:38.910
it's the CROS regimen.

NOTE Confidence: 0.9438593

00:21:39.690 --> 00:21:41.130
And they use something called

NOTE Confidence: 0.9438593

00:21:41.130 --> 00:21:43.230
a stepped wedge clustered randomization,

NOTE Confidence: 0.9956007

00:21:43.530 --> 00:21:45.734
which basically means the patients

NOTE Confidence: 0.9956007

00:21:45.734 --> 00:21:46.635
aren't randomized.

NOTE Confidence: 0.998738

00:21:47.575 --> 00:21:48.875
The twelve hospitals,

NOTE Confidence: 0.99211067

00:21:49.335 --> 00:21:51.175
they only do one or

NOTE Confidence: 0.99211067

00:21:51.175 --> 00:21:51.915
the other,

NOTE Confidence: 0.9876617

00:21:52.455 --> 00:21:54.775
and what they do evolves

NOTE Confidence: 0.9876617

00:21:54.775 --> 00:21:56.455
over time. So everybody that

NOTE Confidence: 0.9876617

00:21:56.455 --> 00:21:58.535
goes to each hospital gets

NOTE Confidence: 0.9876617

00:21:58.535 --> 00:21:59.095
the same,

NOTE Confidence: 0.93957657

00:22:00.160 --> 00:22:01.700
form of treatment, either

NOTE Confidence: 0.89634275

00:22:02.400 --> 00:22:04.420
cross then surgery or cross,

NOTE Confidence: 0.9958711

00:22:04.960 --> 00:22:06.660
versus active surveillance.

NOTE Confidence: 0.99816513

00:22:07.040 --> 00:22:08.340
And every three months,

NOTE Confidence: 0.99610484

00:22:08.960 --> 00:22:09.460
hospitals

NOTE Confidence: 0.99870837

00:22:09.920 --> 00:22:11.060
switch from

NOTE Confidence: 0.93098116

00:22:12.255 --> 00:22:13.155
being a surgery,

NOTE Confidence: 0.9994968

00:22:13.615 --> 00:22:14.595
performing center

NOTE Confidence: 0.9941642

00:22:14.895 --> 00:22:16.195
to one that does surveillance.

NOTE Confidence: 0.9941642

00:22:16.255 --> 00:22:17.855
So anybody who signs up

NOTE Confidence: 0.9941642

00:22:17.855 --> 00:22:18.815
for this trial, they know

NOTE Confidence: 0.9941642

00:22:18.815 --> 00:22:19.715
what they're getting,

NOTE Confidence: 0.971249

00:22:20.095 --> 00:22:21.535
because of the hospital that

NOTE Confidence: 0.971249

00:22:21.535 --> 00:22:23.135
they go to. And then

NOTE Confidence: 0.971249

00:22:23.135 --> 00:22:24.895
eventually, all the hospitals were

NOTE Confidence: 0.971249

00:22:24.895 --> 00:22:27.010
doing active surveillance. So with

NOTE Confidence: 0.971249

00:22:27.010 --> 00:22:28.150
the start of the trial,

NOTE Confidence: 0.971249

00:22:28.210 --> 00:22:30.210
every hospital, all twelve hospitals

NOTE Confidence: 0.971249

00:22:30.210 --> 00:22:31.270
were doing surgery,

NOTE Confidence: 0.84777194

00:22:31.890 --> 00:22:33.030
cross then surgery.

NOTE Confidence: 0.99958277

00:22:33.410 --> 00:22:34.070
And then

NOTE Confidence: 0.99062735

00:22:34.609 --> 00:22:35.670
every three months,

NOTE Confidence: 0.9952687

00:22:36.450 --> 00:22:38.230
two hospitals were randomly

NOTE Confidence: 0.9996173

00:22:38.850 --> 00:22:40.530
assigned to take all their

NOTE Confidence: 0.9996173

00:22:40.530 --> 00:22:41.030
patients

NOTE Confidence: 0.997297

00:22:41.595 --> 00:22:43.515
subsequent to that and do

NOTE Confidence: 0.997297

00:22:43.515 --> 00:22:44.415
active surveillance.

NOTE Confidence: 0.94469756

00:22:44.875 --> 00:22:45.855
And so, eventually,

NOTE Confidence: 0.98197556

00:22:46.475 --> 00:22:47.355
more and more of the

NOTE Confidence: 0.98197556

00:22:47.355 --> 00:22:49.135
hospitals became active surveillance,

NOTE Confidence: 0.99447167

00:22:50.234 --> 00:22:51.515
until all of them were

NOTE Confidence: 0.99447167

00:22:51.515 --> 00:22:53.609
active surveillance. And so it

NOTE Confidence: 0.99447167

00:22:53.609 --> 00:22:55.050
was designed as a two

NOTE Confidence: 0.99447167

00:22:55.050 --> 00:22:57.130
year overall survival from the

NOTE Confidence: 0.99447167

00:22:57.130 --> 00:22:58.250
from the time that they

NOTE Confidence: 0.99447167

00:22:58.250 --> 00:23:00.350
determine a complete clinical response.

NOTE Confidence: 0.9706346

00:23:00.890 --> 00:23:02.650
And it's non inferiority, which

NOTE Confidence: 0.9706346

00:23:02.650 --> 00:23:03.390
means that,

NOTE Confidence: 0.9813873

00:23:04.170 --> 00:23:05.309
they picked a margin.

NOTE Confidence: 0.99106324

00:23:05.770 --> 00:23:07.930
They said fifteen percent. So

NOTE Confidence: 0.99106324

00:23:07.930 --> 00:23:09.744
if the difference in two

NOTE Confidence: 0.99106324

00:23:09.744 --> 00:23:11.285
year survival between

NOTE Confidence: 0.99982685

00:23:11.984 --> 00:23:12.484
surgery

NOTE Confidence: 0.9152618

00:23:12.865 --> 00:23:15.205
as, following cross or

NOTE Confidence: 0.98137826

00:23:15.505 --> 00:23:16.484
active surveillance,

NOTE Confidence: 0.99931824

00:23:17.185 --> 00:23:18.625
if they were within fifteen

NOTE Confidence: 0.99931824

00:23:18.625 --> 00:23:20.244
percentage points of each other,

NOTE Confidence: 0.9617921

00:23:20.705 --> 00:23:22.465
it was not inferior. And

NOTE Confidence: 0.9617921

00:23:22.465 --> 00:23:23.605
it actually it's the

NOTE Confidence: 0.86156464

00:23:23.960 --> 00:23:25.320
upper boundary of the confidence

NOTE Confidence: 0.86156464

00:23:25.320 --> 00:23:27.320
interval by that that's not

NOTE Confidence: 0.86156464

00:23:27.320 --> 00:23:27.820
critical.

NOTE Confidence: 0.9486762

00:23:28.520 --> 00:23:30.520
So they screened about eleven

NOTE Confidence: 0.9486762

00:23:30.520 --> 00:23:32.140
hundred patients. And interestingly,

NOTE Confidence: 0.9992362

00:23:32.600 --> 00:23:34.040
about twenty five percent of

NOTE Confidence: 0.9992362

00:23:34.040 --> 00:23:35.500
all the people they screened

NOTE Confidence: 0.97952276

00:23:36.805 --> 00:23:38.565
did not wanna participate this.

NOTE Confidence: 0.97952276

00:23:38.565 --> 00:23:39.445
And and I think that's

NOTE Confidence: 0.97952276

00:23:39.445 --> 00:23:40.345
just important

NOTE Confidence: 0.97284806

00:23:40.965 --> 00:23:42.244
to sort of understand the

NOTE Confidence: 0.97284806

00:23:42.244 --> 00:23:43.605
appetite. Again, this is not

NOTE Confidence: 0.97284806

00:23:43.605 --> 00:23:45.125
randomized. They they would know

NOTE Confidence: 0.97284806

00:23:45.125 --> 00:23:47.145
what they're getting up front,

NOTE Confidence: 0.9770359

00:23:47.445 --> 00:23:48.825
but they were not interested

NOTE Confidence: 0.9770359

00:23:49.125 --> 00:23:50.585
in in, participating

NOTE Confidence: 0.9977511

00:23:51.125 --> 00:23:52.330
in this. So there were

NOTE Confidence: 0.9977511

00:23:52.330 --> 00:23:53.789
about seven hundred and sixty

NOTE Confidence: 0.9977511

00:23:54.009 --> 00:23:55.629
that underwent that

NOTE Confidence: 0.9985911

00:23:56.090 --> 00:23:56.669
first evaluation,

NOTE Confidence: 0.7647002

00:23:58.250 --> 00:23:58.750
which,

NOTE Confidence: 0.9738487

00:23:59.210 --> 00:24:00.429
was an upper endoscopy,

NOTE Confidence: 0.80774605

00:24:01.769 --> 00:24:02.250
and,

NOTE Confidence: 0.8195065

00:24:02.970 --> 00:24:03.710
an ultrasound.

NOTE Confidence: 0.9973877

00:24:06.184 --> 00:24:07.804
The at that first evaluation,

NOTE Confidence: 0.996169

00:24:08.425 --> 00:24:09.865
thirty six percent were found

NOTE Confidence: 0.996169

00:24:09.865 --> 00:24:11.065
to have cancer in the

NOTE Confidence: 0.996169

00:24:11.065 --> 00:24:12.665
esophagus. So people got their

NOTE Confidence: 0.996169

00:24:12.665 --> 00:24:13.885
chemotherapy and radiation.

NOTE Confidence: 0.9549236

00:24:14.905 --> 00:24:16.445
They had a six week,

NOTE Confidence: 0.9902304

00:24:17.385 --> 00:24:18.505
at the six weeks after

NOTE Confidence: 0.9902304

00:24:18.505 --> 00:24:19.785
the chemotherapy and radiation, they

NOTE Confidence: 0.9902304

00:24:19.785 --> 00:24:20.765
got an upper endoscopy.

NOTE Confidence: 0.98677874

00:24:21.960 --> 00:24:23.080
Just over a third of

NOTE Confidence: 0.98677874

00:24:23.080 --> 00:24:24.840
them, they still had viable

NOTE Confidence: 0.98677874

00:24:24.840 --> 00:24:27.020
cancer in the esophagus. And

NOTE Confidence: 0.98677874

00:24:27.240 --> 00:24:28.460
those that did not

NOTE Confidence: 0.9907781

00:24:28.760 --> 00:24:30.119
went on to the twelve

NOTE Confidence: 0.9907781

00:24:30.119 --> 00:24:32.000
week clinical evaluation, which is

NOTE Confidence: 0.9907781

00:24:32.000 --> 00:24:33.580
a little bit more involved,

NOTE Confidence: 0.9907781

00:24:33.640 --> 00:24:35.345
which was upper endoscopy,

NOTE Confidence: 0.99316067

00:24:35.965 --> 00:24:37.585
ultrasound, and a PET scan.

NOTE Confidence: 0.99316067

00:24:37.804 --> 00:24:38.845
And of the people that

NOTE Confidence: 0.99316067

00:24:38.845 --> 00:24:41.105
underwent that second clinical evaluation,

NOTE Confidence: 0.9293958

00:24:41.804 --> 00:24:43.885
another third were found to

NOTE Confidence: 0.9293958

00:24:43.885 --> 00:24:45.905
have live viable cancer,

NOTE Confidence: 0.9859934

00:24:46.525 --> 00:24:47.825
but forty of them,

NOTE Confidence: 0.9458763

00:24:48.500 --> 00:24:50.260
actually sorry. Forty, forty of

NOTE Confidence: 0.9458763

00:24:50.260 --> 00:24:52.359
them actually had systemic metastases

NOTE Confidence: 0.97454435

00:24:52.980 --> 00:24:54.119
that they were

NOTE Confidence: 0.9397339

00:24:54.500 --> 00:24:56.280
found between their screening

NOTE Confidence: 0.9367807

00:24:56.740 --> 00:24:58.420
and this twelve week clinical

NOTE Confidence: 0.9367807

00:24:58.420 --> 00:24:58.920
evaluation.

NOTE Confidence: 0.9889721

00:24:59.619 --> 00:25:01.380
But they deemed thirty five

NOTE Confidence: 0.9889721

00:25:01.380 --> 00:25:01.880
percent

NOTE Confidence: 0.98886454

00:25:02.855 --> 00:25:04.875
had a complete clinical response,

NOTE Confidence: 0.84445685

00:25:06.695 --> 00:25:07.915
from this this,

NOTE Confidence: 0.9982314

00:25:08.375 --> 00:25:08.875
group.

NOTE Confidence: 0.99893636

00:25:10.295 --> 00:25:11.275
And from this,

NOTE Confidence: 0.9773143

00:25:11.655 --> 00:25:13.175
a hundred and eleven underwent

NOTE Confidence: 0.9773143

00:25:13.175 --> 00:25:14.155
standard surgery.

NOTE Confidence: 0.9563723

00:25:14.560 --> 00:25:15.680
A hundred and ninety eight

NOTE Confidence: 0.9563723

00:25:15.680 --> 00:25:17.600
underwent active surveillance. The numbers

NOTE Confidence: 0.9563723

00:25:17.600 --> 00:25:18.880
don't completely match up because

NOTE Confidence: 0.9563723

00:25:18.880 --> 00:25:19.920
they actually brought in some

NOTE Confidence: 0.9563723

00:25:19.920 --> 00:25:20.740
of the presano

NOTE Confidence: 0.96260893

00:25:21.040 --> 00:25:21.540
patients.

NOTE Confidence: 0.97225386

00:25:22.560 --> 00:25:23.920
And so this was the

NOTE Confidence: 0.97225386

00:25:23.920 --> 00:25:24.420
clinical

NOTE Confidence: 0.95941085

00:25:24.800 --> 00:25:26.800
response assessment. So six weeks

NOTE Confidence: 0.95941085

00:25:26.800 --> 00:25:28.260
after induction therapy,

NOTE Confidence: 0.9943824

00:25:28.675 --> 00:25:29.875
this was the four bite

NOTE Confidence: 0.9943824

00:25:29.875 --> 00:25:30.855
on bite biopsies.

NOTE Confidence: 0.9695611

00:25:32.355 --> 00:25:33.315
And if they didn't see

NOTE Confidence: 0.9695611

00:25:33.315 --> 00:25:34.835
any cancer, they went ongoing,

NOTE Confidence: 0.9926808

00:25:35.315 --> 00:25:36.755
observation. And then at twelve

NOTE Confidence: 0.9926808

00:25:36.755 --> 00:25:38.035
weeks, they added a PET

NOTE Confidence: 0.9926808

00:25:38.035 --> 00:25:38.535
scan

NOTE Confidence: 0.83377534

00:25:38.994 --> 00:25:39.975
and the EUS.

NOTE Confidence: 0.9991692

00:25:40.755 --> 00:25:41.635
And if there were no

NOTE Confidence: 0.9991692

00:25:41.635 --> 00:25:42.994
tumor cells at the twelve

NOTE Confidence: 0.9991692

00:25:42.994 --> 00:25:43.494
weeks,

NOTE Confidence: 0.9890661

00:25:43.940 --> 00:25:45.460
they were deemed a complete,

NOTE Confidence: 0.999382

00:25:45.780 --> 00:25:46.840
clinical responder.

NOTE Confidence: 0.9983688

00:25:49.220 --> 00:25:50.820
And, if you were getting

NOTE Confidence: 0.9983688

00:25:50.820 --> 00:25:51.720
active surveillance,

NOTE Confidence: 0.99838567

00:25:53.299 --> 00:25:53.799
then

NOTE Confidence: 0.97322273

00:25:54.100 --> 00:25:56.025
in year one, you got,

NOTE Confidence: 0.9732704

00:25:56.505 --> 00:25:58.345
the the biopsy, the bite

NOTE Confidence: 0.9732704

00:25:58.345 --> 00:26:00.025
on bite biopsies, the EUS,

NOTE Confidence: 0.9732704

00:26:00.025 --> 00:26:01.305
and the PET scan every

NOTE Confidence: 0.9732704

00:26:01.305 --> 00:26:03.145
three months. Year two is

NOTE Confidence: 0.9732704

00:26:03.145 --> 00:26:04.425
every four months. Year three,

NOTE Confidence: 0.9732704

00:26:04.425 --> 00:26:05.405
every six months.

NOTE Confidence: 0.9955012

00:26:05.705 --> 00:26:06.765
And then after,

NOTE Confidence: 0.99720263

00:26:07.145 --> 00:26:08.265
the third year, it was

NOTE Confidence: 0.99720263

00:26:08.265 --> 00:26:08.765
annually.

NOTE Confidence: 0.9852034

00:26:09.830 --> 00:26:10.710
And when you look at

NOTE Confidence: 0.9852034

00:26:10.710 --> 00:26:12.390
overall survival, this was their

NOTE Confidence: 0.9852034

00:26:12.390 --> 00:26:12.890
endpoint.

NOTE Confidence: 0.99628556

00:26:13.830 --> 00:26:15.510
Seventy four percent of the

NOTE Confidence: 0.99628556

00:26:15.510 --> 00:26:16.410
active surveillance,

NOTE Confidence: 0.9974394

00:26:17.030 --> 00:26:18.390
patients were alive at two

NOTE Confidence: 0.9974394

00:26:18.390 --> 00:26:19.990
years, and seventy one percent

NOTE Confidence: 0.9974394

00:26:19.990 --> 00:26:21.850
of the standard surgery patients

NOTE Confidence: 0.9974394

00:26:22.070 --> 00:26:23.575
were alive. And so this

NOTE Confidence: 0.9974394

00:26:23.575 --> 00:26:24.395
is encouraging

NOTE Confidence: 0.9912815

00:26:24.775 --> 00:26:26.135
that there are people who

NOTE Confidence: 0.9912815

00:26:26.135 --> 00:26:27.915
can be actively surveyed.

NOTE Confidence: 0.9880018

00:26:28.855 --> 00:26:30.055
But I think the real

NOTE Confidence: 0.9880018

00:26:30.055 --> 00:26:31.975
interesting is is how you

NOTE Confidence: 0.9880018

00:26:31.975 --> 00:26:34.215
know, what happened in, to

NOTE Confidence: 0.9880018

00:26:34.215 --> 00:26:35.815
these different patients as they

NOTE Confidence: 0.9880018

00:26:35.815 --> 00:26:37.660
went along. And so if

NOTE Confidence: 0.9880018

00:26:37.660 --> 00:26:39.200
you divide all the patients

NOTE Confidence: 0.9719567

00:26:39.500 --> 00:26:40.940
up into an and put

NOTE Confidence: 0.9719567

00:26:40.940 --> 00:26:42.380
them into the a, into

NOTE Confidence: 0.9719567

00:26:42.380 --> 00:26:44.300
the the pie chart, you

NOTE Confidence: 0.9719567

00:26:44.300 --> 00:26:45.020
can get rid of the

NOTE Confidence: 0.9719567

00:26:45.020 --> 00:26:46.700
people who were excluded for

NOTE Confidence: 0.9719567

00:26:46.700 --> 00:26:48.160
sort of technical reasons.

NOTE Confidence: 0.9954362

00:26:50.145 --> 00:26:52.165
Fifty five percent of patients

NOTE Confidence: 0.988472

00:26:52.545 --> 00:26:54.145
had before they could get

NOTE Confidence: 0.988472

00:26:54.145 --> 00:26:56.065
randomized or before they were,

NOTE Confidence: 0.9841471

00:26:57.105 --> 00:26:58.225
made it to the point

NOTE Confidence: 0.9841471

00:26:58.225 --> 00:26:58.965
of being,

NOTE Confidence: 0.9914664

00:26:59.984 --> 00:27:01.505
assigned to one of the,

NOTE Confidence: 0.9914664

00:27:01.825 --> 00:27:02.565
two groups,

NOTE Confidence: 0.98706853

00:27:03.070 --> 00:27:04.910
they had viable cancer. About

NOTE Confidence: 0.98706853

00:27:04.910 --> 00:27:06.609
a third at each checkpoint,

NOTE Confidence: 0.9841337

00:27:07.550 --> 00:27:08.910
and then five percent had

NOTE Confidence: 0.9841337

00:27:08.910 --> 00:27:09.410
mets,

NOTE Confidence: 0.8412547

00:27:10.830 --> 00:27:13.250
systemic mets during this evaluation.

NOTE Confidence: 0.9763624

00:27:14.109 --> 00:27:14.910
And then if you look

NOTE Confidence: 0.9763624

00:27:14.910 --> 00:27:16.850
at the groups that underwent,

NOTE Confidence: 0.9993073

00:27:17.895 --> 00:27:19.734
either the active surveillance or

NOTE Confidence: 0.9993073

00:27:19.734 --> 00:27:20.875
the standard surgery,

NOTE Confidence: 0.99921286

00:27:21.975 --> 00:27:23.675
it's a much smaller subset.

NOTE Confidence: 0.99967134

00:27:24.295 --> 00:27:25.655
And if we really focus

NOTE Confidence: 0.99967134

00:27:25.655 --> 00:27:27.734
on the active surveillance group,

NOTE Confidence: 0.98314166

00:27:28.055 --> 00:27:29.095
which is about a quarter

NOTE Confidence: 0.98314166

00:27:29.095 --> 00:27:30.635
of the patients that started

NOTE Confidence: 0.98314166

00:27:30.695 --> 00:27:31.515
all of this,

NOTE Confidence: 0.95597863

00:27:31.940 --> 00:27:33.320
and break them down,

NOTE Confidence: 0.99576133

00:27:34.580 --> 00:27:35.799
you can see that

NOTE Confidence: 0.946577

00:27:36.660 --> 00:27:38.100
about four percent of them

NOTE Confidence: 0.946577

00:27:38.100 --> 00:27:38.600
developed

NOTE Confidence: 0.5473364

00:27:38.980 --> 00:27:39.480
METs,

NOTE Confidence: 0.9410504

00:27:40.020 --> 00:27:41.000
systemic metastases,

NOTE Confidence: 0.94738007

00:27:41.380 --> 00:27:42.340
why they were while they

NOTE Confidence: 0.94738007

00:27:42.340 --> 00:27:43.960
were undergoing active surveillance.

NOTE Confidence: 0.99024

00:27:45.625 --> 00:27:47.625
Local only failure means they

NOTE Confidence: 0.99024

00:27:47.625 --> 00:27:48.984
found the cancer in the

NOTE Confidence: 0.99024

00:27:48.984 --> 00:27:50.765
esophagus, but nowhere else.

NOTE Confidence: 0.99777955

00:27:51.145 --> 00:27:52.585
That happened twelve percent of

NOTE Confidence: 0.99777955

00:27:52.585 --> 00:27:53.244
the time.

NOTE Confidence: 0.9860402

00:27:53.945 --> 00:27:55.145
Ten percent of them went

NOTE Confidence: 0.9860402

00:27:55.145 --> 00:27:56.425
on to surgery, while two

NOTE Confidence: 0.9860402

00:27:56.425 --> 00:27:57.725
percent did not.

NOTE Confidence: 0.974023

00:27:58.070 --> 00:27:58.970
And then eight percent,

NOTE Confidence: 0.982916

00:28:00.150 --> 00:28:00.809
of patients,

NOTE Confidence: 0.9447732

00:28:01.350 --> 00:28:02.869
there was no cancer in

NOTE Confidence: 0.9447732

00:28:02.869 --> 00:28:04.570
the two years of observation.

NOTE Confidence: 0.9861695

00:28:04.869 --> 00:28:06.470
They had no cancer no

NOTE Confidence: 0.9861695

00:28:06.470 --> 00:28:07.910
return of cancer. And if

NOTE Confidence: 0.9861695

00:28:07.910 --> 00:28:09.030
we just look at the

NOTE Confidence: 0.9861695

00:28:09.030 --> 00:28:10.890
people who underwent active surveillance

NOTE Confidence: 0.93703717

00:28:11.510 --> 00:28:12.790
and just look at that

NOTE Confidence: 0.93703717

00:28:12.790 --> 00:28:13.290
subset,

NOTE Confidence: 0.99096465

00:28:14.115 --> 00:28:15.395
So forty two percent of

NOTE Confidence: 0.99096465

00:28:15.395 --> 00:28:17.095
patients underwent surgery,

NOTE Confidence: 0.94000334

00:28:18.275 --> 00:28:18.775
eventually,

NOTE Confidence: 0.8176488

00:28:19.555 --> 00:28:20.915
as for a median about

NOTE Confidence: 0.8176488

00:28:20.915 --> 00:28:21.734
six months.

NOTE Confidence: 0.99374354

00:28:22.675 --> 00:28:23.955
About seventeen percent of the

NOTE Confidence: 0.99374354

00:28:23.955 --> 00:28:25.815
people that underwent active surveillance

NOTE Confidence: 0.7401787

00:28:26.460 --> 00:28:27.520
developed metastases,

NOTE Confidence: 0.9953182

00:28:28.380 --> 00:28:30.460
and seven percent developed local

NOTE Confidence: 0.9953182

00:28:30.460 --> 00:28:32.140
only failure. Cancer came back

NOTE Confidence: 0.9953182

00:28:32.140 --> 00:28:33.039
in the esophagus,

NOTE Confidence: 0.9997168

00:28:33.580 --> 00:28:34.940
but they opted not to

NOTE Confidence: 0.9997168

00:28:34.940 --> 00:28:35.679
have surgery.

NOTE Confidence: 0.99513066

00:28:36.140 --> 00:28:37.179
So I think this is

NOTE Confidence: 0.99513066

00:28:37.179 --> 00:28:38.799
kind of an interesting perspective

NOTE Confidence: 0.99513066

00:28:38.860 --> 00:28:40.299
of things. So the first

NOTE Confidence: 0.99513066

00:28:40.299 --> 00:28:41.419
thing is if these people

NOTE Confidence: 0.99513066

00:28:41.419 --> 00:28:41.919
waited

NOTE Confidence: 0.99676096

00:28:42.674 --> 00:28:43.335
six months,

NOTE Confidence: 0.95881844

00:28:44.034 --> 00:28:45.794
were there any downside to

NOTE Confidence: 0.95881844

00:28:45.794 --> 00:28:46.835
waiting? Because why not just

NOTE Confidence: 0.95881844

00:28:46.835 --> 00:28:47.955
do this for everybody if

NOTE Confidence: 0.95881844

00:28:47.955 --> 00:28:48.934
there's no downside

NOTE Confidence: 0.8619766

00:28:49.715 --> 00:28:50.375
to waiting?

NOTE Confidence: 0.95967746

00:28:51.154 --> 00:28:52.514
Even if it's a very

NOTE Confidence: 0.95967746

00:28:52.514 --> 00:28:54.195
small percentage of patients that

NOTE Confidence: 0.95967746

00:28:54.195 --> 00:28:55.335
can avoid surgery,

NOTE Confidence: 0.9955155

00:28:55.920 --> 00:28:57.760
Why not? And so the

NOTE Confidence: 0.9955155

00:28:57.760 --> 00:28:59.120
concern is that if you

NOTE Confidence: 0.9955155

00:28:59.120 --> 00:29:01.300
wait longer, people can develop

NOTE Confidence: 0.9955155

00:29:01.360 --> 00:29:03.600
metastases that they otherwise would

NOTE Confidence: 0.9955155

00:29:03.600 --> 00:29:04.820
not have. And so

NOTE Confidence: 0.9565782

00:29:05.360 --> 00:29:06.580
there was a difference,

NOTE Confidence: 0.97907

00:29:07.040 --> 00:29:08.900
that was not statistically significant,

NOTE Confidence: 0.97907

00:29:09.040 --> 00:29:10.080
but a but a trend

NOTE Confidence: 0.97907

00:29:10.080 --> 00:29:11.355
for a difference at thirty

NOTE Confidence: 0.97907

00:29:11.355 --> 00:29:11.855
months,

NOTE Confidence: 0.9685672

00:29:13.035 --> 00:29:14.555
difference in the,

NOTE Confidence: 0.98097694

00:29:14.955 --> 00:29:16.735
the rate of distant metastases,

NOTE Confidence: 0.9994965

00:29:17.515 --> 00:29:18.875
forty three percent for the

NOTE Confidence: 0.9994965

00:29:18.875 --> 00:29:19.375
surveillance

NOTE Confidence: 0.9831386

00:29:19.755 --> 00:29:21.295
group, and thirty four percent

NOTE Confidence: 0.9831386

00:29:21.595 --> 00:29:23.115
for the standard surgery. This

NOTE Confidence: 0.9831386

00:29:23.115 --> 00:29:25.115
was not statistically significant, but

NOTE Confidence: 0.9831386

00:29:25.115 --> 00:29:25.675
it is a

NOTE Confidence: 0.99608374

00:29:26.690 --> 00:29:27.590
it it's approaching

NOTE Confidence: 0.9898677

00:29:27.970 --> 00:29:29.910
significance in in my mind.

NOTE Confidence: 0.9640367

00:29:31.090 --> 00:29:31.970
And if you look at

NOTE Confidence: 0.9640367

00:29:31.970 --> 00:29:33.270
the disease free survival,

NOTE Confidence: 0.99953824

00:29:34.130 --> 00:29:35.890
there is no difference in

NOTE Confidence: 0.99953824

00:29:35.890 --> 00:29:36.390
the

NOTE Confidence: 0.97103935

00:29:36.770 --> 00:29:38.450
period that was observed. But

NOTE Confidence: 0.97103935

00:29:38.450 --> 00:29:39.925
if you look, they are

NOTE Confidence: 0.97103935

00:29:39.925 --> 00:29:41.685
starting to separate after two

NOTE Confidence: 0.97103935

00:29:41.685 --> 00:29:43.125
years. You are starting to

NOTE Confidence: 0.97103935

00:29:43.125 --> 00:29:43.625
see

NOTE Confidence: 0.9684902

00:29:44.085 --> 00:29:45.065
a bit more,

NOTE Confidence: 0.9989688

00:29:45.765 --> 00:29:47.465
of a disease free survival

NOTE Confidence: 0.9554639

00:29:47.845 --> 00:29:48.345
trend,

NOTE Confidence: 0.9994974

00:29:48.965 --> 00:29:50.165
in the people that had

NOTE Confidence: 0.9994974

00:29:50.165 --> 00:29:50.665
surgery.

NOTE Confidence: 0.9892225

00:29:51.445 --> 00:29:52.185
And so

NOTE Confidence: 0.9745094

00:29:53.090 --> 00:29:54.130
in sort of putting this

NOTE Confidence: 0.9745094

00:29:54.130 --> 00:29:55.650
together, forty five percent of

NOTE Confidence: 0.9745094

00:29:55.650 --> 00:29:57.490
people, if you do the

NOTE Confidence: 0.9745094

00:29:57.490 --> 00:29:58.630
SANO protocol,

NOTE Confidence: 0.88504374

00:29:59.490 --> 00:30:00.390
give CROS,

NOTE Confidence: 0.9519479

00:30:00.770 --> 00:30:01.510
and then,

NOTE Confidence: 0.9639753

00:30:02.690 --> 00:30:03.510
do these,

NOTE Confidence: 0.9917889

00:30:04.050 --> 00:30:04.950
serial endoscopies,

NOTE Confidence: 0.9827587

00:30:05.730 --> 00:30:07.425
six weeks and twelve weeks,

NOTE Confidence: 0.9827587

00:30:07.505 --> 00:30:09.025
you're gonna find a complete

NOTE Confidence: 0.9827587

00:30:09.025 --> 00:30:10.545
clinical response in about forty

NOTE Confidence: 0.9827587

00:30:10.545 --> 00:30:11.685
five percent of people,

NOTE Confidence: 0.99912894

00:30:12.225 --> 00:30:13.765
but two thirds of them

NOTE Confidence: 0.98846745

00:30:14.065 --> 00:30:15.445
actually still have cancer.

NOTE Confidence: 0.9976707

00:30:16.465 --> 00:30:17.905
And about sixteen percent of

NOTE Confidence: 0.9976707

00:30:17.905 --> 00:30:19.365
people seem to be

NOTE Confidence: 0.9997332

00:30:19.745 --> 00:30:20.805
disease free

NOTE Confidence: 0.76636404

00:30:21.425 --> 00:30:22.325
after cross

NOTE Confidence: 0.99573463

00:30:22.705 --> 00:30:24.120
only. So if you just

NOTE Confidence: 0.99573463

00:30:24.120 --> 00:30:25.340
give people chemoradiation,

NOTE Confidence: 0.99103373

00:30:26.120 --> 00:30:27.340
predominantly adenocarcinoma,

NOTE Confidence: 0.9993347

00:30:27.640 --> 00:30:29.260
about sixteen percent of people

NOTE Confidence: 0.9729315

00:30:29.880 --> 00:30:31.720
are alive and disease free

NOTE Confidence: 0.9729315

00:30:31.720 --> 00:30:33.560
at two years. So it's

NOTE Confidence: 0.9729315

00:30:33.560 --> 00:30:34.680
not a huge number, but

NOTE Confidence: 0.9729315

00:30:34.680 --> 00:30:36.280
it is the it is

NOTE Confidence: 0.9729315

00:30:36.280 --> 00:30:36.940
a number,

NOTE Confidence: 0.87888175

00:30:37.720 --> 00:30:38.940
a reasonable number.

NOTE Confidence: 0.97834647

00:30:39.405 --> 00:30:40.065
And so,

NOTE Confidence: 0.97622484

00:30:41.005 --> 00:30:42.465
you know, again, because,

NOTE Confidence: 0.9734676

00:30:43.085 --> 00:30:44.685
of people with persistent cancer,

NOTE Confidence: 0.9734676

00:30:44.685 --> 00:30:46.605
people that develop metastases, people

NOTE Confidence: 0.9734676

00:30:46.605 --> 00:30:48.365
who have recurrent cancer who

NOTE Confidence: 0.9734676

00:30:48.365 --> 00:30:49.505
were once cleared,

NOTE Confidence: 0.972903

00:30:50.685 --> 00:30:52.125
that's sort of the impact.

NOTE Confidence: 0.972903

00:30:52.125 --> 00:30:53.665
So we're you're really deferring

NOTE Confidence: 0.972903

00:30:53.725 --> 00:30:54.225
treatment

NOTE Confidence: 0.99051374

00:30:55.420 --> 00:30:56.860
for the possibility that people

NOTE Confidence: 0.99051374

00:30:56.860 --> 00:30:58.060
have been cured with their

NOTE Confidence: 0.99051374

00:30:58.060 --> 00:30:58.560
nonsurgical

NOTE Confidence: 0.9926735

00:30:59.020 --> 00:30:59.520
approach.

NOTE Confidence: 0.98718846

00:31:00.540 --> 00:31:02.240
And this is not terribly

NOTE Confidence: 0.98718846

00:31:02.460 --> 00:31:04.060
different from what we would

NOTE Confidence: 0.98718846

00:31:04.060 --> 00:31:05.180
see we saw in the

NOTE Confidence: 0.98718846

00:31:05.180 --> 00:31:07.360
German trial with chemo radiation

NOTE Confidence: 0.98866427

00:31:08.225 --> 00:31:08.725
alone.

NOTE Confidence: 0.9697684

00:31:09.745 --> 00:31:11.105
The French trial was a

NOTE Confidence: 0.9697684

00:31:11.105 --> 00:31:12.565
little bit, better

NOTE Confidence: 0.9512028

00:31:12.945 --> 00:31:15.045
in terms of, survival. But

NOTE Confidence: 0.9512028

00:31:15.265 --> 00:31:17.345
sixteen percent cure rate,

NOTE Confidence: 0.93695664

00:31:17.825 --> 00:31:18.565
is not,

NOTE Confidence: 0.9088847

00:31:19.425 --> 00:31:20.305
is is it you know,

NOTE Confidence: 0.9088847

00:31:20.305 --> 00:31:21.505
sixteen to twenty percent, I

NOTE Confidence: 0.9088847

00:31:21.505 --> 00:31:22.565
think, is a reasonable

NOTE Confidence: 0.9993412

00:31:23.480 --> 00:31:23.980
expectation

NOTE Confidence: 0.9707614

00:31:24.440 --> 00:31:27.260
for nonsurgically managed, particularly adenocarcinoma.

NOTE Confidence: 0.9921823

00:31:28.680 --> 00:31:30.040
But there were people that

NOTE Confidence: 0.9921823

00:31:30.040 --> 00:31:31.560
surgery is unlikely to help,

NOTE Confidence: 0.9921823

00:31:31.560 --> 00:31:33.720
people that develop metastases, and

NOTE Confidence: 0.9921823

00:31:33.720 --> 00:31:34.920
there were some people that

NOTE Confidence: 0.9921823

00:31:34.920 --> 00:31:36.520
were cured. And when you

NOTE Confidence: 0.9921823

00:31:36.520 --> 00:31:38.300
add all of those up,

NOTE Confidence: 0.95019454

00:31:39.105 --> 00:31:40.385
you know, there is probably

NOTE Confidence: 0.95019454

00:31:40.385 --> 00:31:42.005
a twenty, twenty five percent,

NOTE Confidence: 0.9777635

00:31:43.745 --> 00:31:44.705
if not a few more

NOTE Confidence: 0.9777635

00:31:44.705 --> 00:31:46.065
that surgery is really not

NOTE Confidence: 0.9777635

00:31:46.065 --> 00:31:47.745
helping. And the question is,

NOTE Confidence: 0.9777635

00:31:47.745 --> 00:31:48.945
can you figure this out?

NOTE Confidence: 0.9777635

00:31:48.945 --> 00:31:49.905
If you knew this ahead

NOTE Confidence: 0.9777635

00:31:49.905 --> 00:31:51.185
of time, who could who

NOTE Confidence: 0.9777635

00:31:51.185 --> 00:31:52.725
was cured by nonsurgical

NOTE Confidence: 0.9893162

00:31:53.025 --> 00:31:54.899
treatment and who was just

NOTE Confidence: 0.9893162

00:31:54.899 --> 00:31:55.399
incurable,

NOTE Confidence: 0.97806865

00:31:56.179 --> 00:31:57.220
that would be very helpful.

NOTE Confidence: 0.97806865

00:31:57.220 --> 00:31:58.019
And I think this is

NOTE Confidence: 0.97806865

00:31:58.019 --> 00:31:59.620
where the most exciting research

NOTE Confidence: 0.97806865

00:31:59.620 --> 00:32:00.820
is coming because this is

NOTE Confidence: 0.97806865

00:32:00.820 --> 00:32:01.940
going to happen in our

NOTE Confidence: 0.97806865

00:32:01.940 --> 00:32:02.440
lifetime,

NOTE Confidence: 0.9736802

00:32:03.460 --> 00:32:05.240
perhaps with cell free DNA,

NOTE Confidence: 0.9415818

00:32:06.914 --> 00:32:08.914
probably not with circulating tumor

NOTE Confidence: 0.9415818

00:32:08.914 --> 00:32:10.434
cells, which was some of

NOTE Confidence: 0.9415818

00:32:10.434 --> 00:32:11.735
my research, unfortunately.

NOTE Confidence: 0.9859126

00:32:12.275 --> 00:32:14.195
But I think AI looking

NOTE Confidence: 0.9859126

00:32:14.195 --> 00:32:15.794
at using AI to look

NOTE Confidence: 0.9859126

00:32:15.794 --> 00:32:16.934
at a lot of,

NOTE Confidence: 0.98887444

00:32:17.554 --> 00:32:18.615
either radiomics

NOTE Confidence: 0.99472517

00:32:19.075 --> 00:32:19.575
or

NOTE Confidence: 0.95637155

00:32:22.320 --> 00:32:22.820
micrographs.

NOTE Confidence: 0.9963859

00:32:23.840 --> 00:32:25.380
I do think there's enormous

NOTE Confidence: 0.9963859

00:32:25.520 --> 00:32:26.020
potential

NOTE Confidence: 0.9810232

00:32:26.720 --> 00:32:28.640
to understand what's going on

NOTE Confidence: 0.9810232

00:32:28.640 --> 00:32:30.240
with our cancers and our

NOTE Confidence: 0.9810232

00:32:30.240 --> 00:32:30.740
treatment,

NOTE Confidence: 0.99776375

00:32:31.679 --> 00:32:33.120
so that we can much

NOTE Confidence: 0.99776375

00:32:33.120 --> 00:32:35.040
more accurately assess things. And

NOTE Confidence: 0.99776375

00:32:35.040 --> 00:32:36.515
so just to close,

NOTE Confidence: 0.9845078

00:32:37.055 --> 00:32:38.675
again, coming back to the

NOTE Confidence: 0.9845078

00:32:38.815 --> 00:32:40.415
the horrors of what is

NOTE Confidence: 0.9845078

00:32:40.415 --> 00:32:41.155
an esophagectomy,

NOTE Confidence: 0.998901

00:32:43.215 --> 00:32:44.255
I I just think it's

NOTE Confidence: 0.998901

00:32:44.255 --> 00:32:46.115
a different era. I think

NOTE Confidence: 0.9974014

00:32:46.495 --> 00:32:46.995
esophagectomies

NOTE Confidence: 0.9997845

00:32:47.455 --> 00:32:48.655
can be done safely. I

NOTE Confidence: 0.9997845

00:32:48.655 --> 00:32:50.175
think people can return to

NOTE Confidence: 0.9997845

00:32:50.175 --> 00:32:51.475
their quality of life

NOTE Confidence: 0.95426214

00:32:51.799 --> 00:32:53.740
as, as an expectation.

NOTE Confidence: 0.98304546

00:32:55.000 --> 00:32:56.280
But I do think this

NOTE Confidence: 0.98304546

00:32:56.280 --> 00:32:57.480
is a Henry Ford quote.

NOTE Confidence: 0.98304546

00:32:57.480 --> 00:32:58.360
Whether you think it can

NOTE Confidence: 0.98304546

00:32:58.360 --> 00:32:59.320
be done or you do

NOTE Confidence: 0.98304546

00:32:59.320 --> 00:32:59.820
not,

NOTE Confidence: 0.99927366

00:33:00.360 --> 00:33:01.880
you are probably right. I

NOTE Confidence: 0.99927366

00:33:01.880 --> 00:33:02.620
think that

NOTE Confidence: 0.940244

00:33:03.904 --> 00:33:04.404
there

NOTE Confidence: 0.997559

00:33:04.865 --> 00:33:06.144
it is not a given

NOTE Confidence: 0.997559

00:33:06.144 --> 00:33:06.625
that,

NOTE Confidence: 0.99936074

00:33:06.945 --> 00:33:08.304
that your surgery is gonna

NOTE Confidence: 0.99936074

00:33:08.304 --> 00:33:09.345
be done in a way

NOTE Confidence: 0.99936074

00:33:09.345 --> 00:33:10.784
that's gonna leave you highly

NOTE Confidence: 0.99936074

00:33:10.784 --> 00:33:11.284
functional.

NOTE Confidence: 0.9808448

00:33:12.144 --> 00:33:13.044
I think Connecticut,

NOTE Confidence: 0.9998648

00:33:13.664 --> 00:33:15.125
is blessed to have

NOTE Confidence: 0.94678783

00:33:16.799 --> 00:33:18.500
a a number of talented,

NOTE Confidence: 0.99126846

00:33:19.120 --> 00:33:21.779
teams, that perform esophageal cancer.

NOTE Confidence: 0.9665495

00:33:22.559 --> 00:33:23.760
We are a three star

NOTE Confidence: 0.9665495

00:33:23.760 --> 00:33:24.880
program for the Society of

NOTE Confidence: 0.9665495

00:33:24.880 --> 00:33:26.080
Thoracic Surgeons, but I can

NOTE Confidence: 0.9665495

00:33:26.080 --> 00:33:27.220
tell you we've trained,

NOTE Confidence: 0.97539717

00:33:27.840 --> 00:33:28.720
a lot of people in

NOTE Confidence: 0.97539717

00:33:28.720 --> 00:33:29.679
the state, and we are

NOTE Confidence: 0.97539717

00:33:29.679 --> 00:33:30.240
not the only,

NOTE Confidence: 0.9950011

00:33:30.945 --> 00:33:31.985
we're not the only group

NOTE Confidence: 0.9950011

00:33:31.985 --> 00:33:33.605
that does this, well.

NOTE Confidence: 0.98304176

00:33:34.065 --> 00:33:34.565
So

NOTE Confidence: 0.97702026

00:33:35.024 --> 00:33:35.684
thank you,

NOTE Confidence: 0.9999101

00:33:36.065 --> 00:33:36.804
very much.

NOTE Confidence: 0.9466847

00:33:39.105 --> 00:33:40.884
Thanks very much, doctor Buffet,

NOTE Confidence: 0.9928713

00:33:41.264 --> 00:33:43.264
for reinforcing the importance of

NOTE Confidence: 0.9928713

00:33:43.264 --> 00:33:44.625
surgery in in this very

NOTE Confidence: 0.9928713

00:33:44.625 --> 00:33:46.590
difficult to treat, tumor type.

NOTE Confidence: 0.9685074

00:33:49.470 --> 00:33:51.230
No questions? Okay. Next, we

NOTE Confidence: 0.9685074

00:33:51.230 --> 00:33:52.429
move on to doctor Du.

NOTE Confidence: 0.9685074

00:33:52.429 --> 00:33:53.470
He's gonna talk to us

NOTE Confidence: 0.9685074

00:33:53.470 --> 00:33:55.090
about the advances in radiation

NOTE Confidence: 0.9685074

00:33:55.150 --> 00:33:55.650
oncology.

NOTE Confidence: 0.94694513

00:33:59.245 --> 00:34:00.625
Okay. Hello, everyone.

NOTE Confidence: 0.9922366

00:34:01.405 --> 00:34:03.405
I'm just going to share

NOTE Confidence: 0.9922366

00:34:03.405 --> 00:34:04.705
my slides here.

NOTE Confidence: 0.97506094

00:34:05.965 --> 00:34:06.465
And,

NOTE Confidence: 0.98332995

00:34:07.085 --> 00:34:08.385
are you seeing my presentation

NOTE Confidence: 0.98332995

00:34:08.605 --> 00:34:09.105
page?

NOTE Confidence: 0.85860324

00:34:10.285 --> 00:34:11.244
I think you need to

NOTE Confidence: 0.85860324

00:34:11.244 --> 00:34:12.844
swap it, Kevin. Okay. Got

NOTE Confidence: 0.85860324

00:34:12.844 --> 00:34:13.665
it. Sorry.

NOTE Confidence: 0.88501173

00:34:26.010 --> 00:34:26.325
Let's,

NOTE Confidence: 0.9955907

00:34:34.484 --> 00:34:35.385
There you go.

NOTE Confidence: 0.9964014

00:34:36.005 --> 00:34:36.505
Okay.

NOTE Confidence: 0.98043716

00:34:37.204 --> 00:34:38.405
So my name is Kevin

NOTE Confidence: 0.98043716

00:34:38.405 --> 00:34:39.945
Du, and, I'm

NOTE Confidence: 0.99901706

00:34:40.310 --> 00:34:41.050
one of the

NOTE Confidence: 0.8267833

00:34:41.350 --> 00:34:42.410
radiation oncologists

NOTE Confidence: 0.90305704

00:34:42.790 --> 00:34:44.650
in the department of therapeutic

NOTE Confidence: 0.90305704

00:34:44.710 --> 00:34:45.210
radiology,

NOTE Confidence: 0.96339506

00:34:46.150 --> 00:34:47.750
here at Yale and, also

NOTE Confidence: 0.96339506

00:34:47.750 --> 00:34:49.350
medical director of the Trumbull

NOTE Confidence: 0.96339506

00:34:49.350 --> 00:34:50.869
Radiation Oncology Center at the

NOTE Confidence: 0.96339506

00:34:50.869 --> 00:34:51.690
Park Avenue,

NOTE Confidence: 0.94953036

00:34:51.989 --> 00:34:52.890
Medical Center.

NOTE Confidence: 0.99657947

00:34:53.590 --> 00:34:54.090
So

NOTE Confidence: 0.9707493

00:34:54.675 --> 00:34:56.355
it's really nice to, spend

NOTE Confidence: 0.9707493

00:34:56.355 --> 00:34:57.555
some time here talking with

NOTE Confidence: 0.9707493

00:34:57.555 --> 00:34:58.275
you about,

NOTE Confidence: 0.9648293

00:34:59.075 --> 00:35:01.415
radiation treatment for esophageal cancer.

NOTE Confidence: 0.91182536

00:35:02.114 --> 00:35:04.035
And, for unfortunately, I have

NOTE Confidence: 0.91182536

00:35:04.035 --> 00:35:04.775
no disclosures.

NOTE Confidence: 0.99150413

00:35:05.875 --> 00:35:06.375
The

NOTE Confidence: 0.7734925

00:35:07.290 --> 00:35:09.050
modern radiation therapy, I just

NOTE Confidence: 0.8473615

00:35:09.530 --> 00:35:10.350
a word,

NOTE Confidence: 0.9826924

00:35:10.730 --> 00:35:11.690
to give you my thoughts

NOTE Confidence: 0.9826924

00:35:11.690 --> 00:35:13.130
is really, I think, you

NOTE Confidence: 0.9826924

00:35:13.130 --> 00:35:14.650
know, all about trying to

NOTE Confidence: 0.9826924

00:35:14.650 --> 00:35:15.150
use

NOTE Confidence: 0.83936524

00:35:15.610 --> 00:35:16.830
radiation biology,

NOTE Confidence: 0.91227627

00:35:17.530 --> 00:35:19.469
advances in physics and computing

NOTE Confidence: 0.91227627

00:35:19.610 --> 00:35:20.110
technology

NOTE Confidence: 0.99875855

00:35:20.755 --> 00:35:21.494
to really

NOTE Confidence: 0.96470207

00:35:22.355 --> 00:35:24.994
improve our therapeutic index. And,

NOTE Confidence: 0.96470207

00:35:25.155 --> 00:35:26.195
there's been a lot of

NOTE Confidence: 0.96470207

00:35:26.195 --> 00:35:28.215
really incredible advances in radiation

NOTE Confidence: 0.9804943

00:35:28.675 --> 00:35:30.375
in the past twenty years.

NOTE Confidence: 0.9365997

00:35:31.155 --> 00:35:33.075
And, really, ultimately, you know,

NOTE Confidence: 0.9365997

00:35:33.075 --> 00:35:34.650
the the kind of the

NOTE Confidence: 0.9365997

00:35:34.650 --> 00:35:35.930
the holy grail for for

NOTE Confidence: 0.9365997

00:35:35.930 --> 00:35:37.130
radiation is really how can

NOTE Confidence: 0.9365997

00:35:37.130 --> 00:35:38.589
we improve functional

NOTE Confidence: 0.9343601

00:35:39.210 --> 00:35:40.829
preservation, organ preservation,

NOTE Confidence: 0.8788292

00:35:41.690 --> 00:35:43.950
and how can we improve

NOTE Confidence: 0.955563

00:35:44.489 --> 00:35:46.570
pathologic complete response and cure

NOTE Confidence: 0.955563

00:35:46.570 --> 00:35:48.030
more patients with radiation.

NOTE Confidence: 0.9700335

00:35:48.895 --> 00:35:49.215
And,

NOTE Confidence: 0.9820822

00:35:49.695 --> 00:35:51.375
so for esophageal cancer, this

NOTE Confidence: 0.9820822

00:35:51.375 --> 00:35:52.995
has actually been looked at

NOTE Confidence: 0.9293524

00:35:53.375 --> 00:35:55.055
really quite a bit in,

NOTE Confidence: 0.9293524

00:35:55.455 --> 00:35:57.215
in in the past, forty

NOTE Confidence: 0.9293524

00:35:57.215 --> 00:35:58.195
years or so.

NOTE Confidence: 0.89959097

00:35:58.495 --> 00:36:00.415
And, just to kind of,

NOTE Confidence: 0.89959097

00:36:00.575 --> 00:36:01.075
give

NOTE Confidence: 0.82076246

00:36:01.535 --> 00:36:03.955
a basic overview, everyone, I

NOTE Confidence: 0.97801113

00:36:04.460 --> 00:36:05.739
I I think, may may

NOTE Confidence: 0.97801113

00:36:05.739 --> 00:36:07.359
be familiar with this, but

NOTE Confidence: 0.97801113

00:36:07.420 --> 00:36:08.700
we have two different types

NOTE Confidence: 0.97801113

00:36:08.700 --> 00:36:10.779
of esophageal cancers. And and,

NOTE Confidence: 0.97801113

00:36:10.779 --> 00:36:12.140
really, in the modern era

NOTE Confidence: 0.97801113

00:36:12.140 --> 00:36:13.900
of esophageal cancer treatment, we

NOTE Confidence: 0.97801113

00:36:13.900 --> 00:36:15.660
approach each one differently in

NOTE Confidence: 0.97801113

00:36:15.660 --> 00:36:16.700
terms of how we think

NOTE Confidence: 0.97801113

00:36:16.700 --> 00:36:18.239
about radiation. So,

NOTE Confidence: 0.99466515

00:36:18.894 --> 00:36:20.994
squamous cell cancers and adenocarcinomas

NOTE Confidence: 0.98722965

00:36:21.694 --> 00:36:22.914
being the two histologies.

NOTE Confidence: 0.94850653

00:36:23.614 --> 00:36:24.894
And then we also think

NOTE Confidence: 0.94850653

00:36:24.894 --> 00:36:26.355
when we think about considerations

NOTE Confidence: 0.94850653

00:36:26.575 --> 00:36:27.234
of radiation,

NOTE Confidence: 0.9759303

00:36:27.775 --> 00:36:28.734
what the look where the

NOTE Confidence: 0.9759303

00:36:28.734 --> 00:36:30.335
location of the cancer is.

NOTE Confidence: 0.9759303

00:36:30.335 --> 00:36:31.375
Is it in the upper

NOTE Confidence: 0.9759303

00:36:31.375 --> 00:36:32.434
cervical esophagus,

NOTE Confidence: 0.99494123

00:36:32.790 --> 00:36:34.710
the middle thoracic, or lower

NOTE Confidence: 0.99494123

00:36:34.710 --> 00:36:35.210
thoracic

NOTE Confidence: 0.6918688

00:36:36.469 --> 00:36:36.969
locations,

NOTE Confidence: 0.99430895

00:36:37.670 --> 00:36:39.610
and how that might affect

NOTE Confidence: 0.885874

00:36:40.630 --> 00:36:42.090
radiation decision making?

NOTE Confidence: 0.97016466

00:36:43.350 --> 00:36:45.030
And, over the years, you

NOTE Confidence: 0.97016466

00:36:45.030 --> 00:36:46.404
know, we've used a lot

NOTE Confidence: 0.97016466

00:36:46.404 --> 00:36:48.565
of different regimens. But as,

NOTE Confidence: 0.97016466

00:36:48.805 --> 00:36:51.065
this panel shows, we've really

NOTE Confidence: 0.9254551

00:36:51.765 --> 00:36:52.884
focused a lot in the

NOTE Confidence: 0.9254551

00:36:52.884 --> 00:36:54.424
United States and,

NOTE Confidence: 0.54207313

00:36:55.285 --> 00:36:56.025
and Europe

NOTE Confidence: 0.99338007

00:36:56.325 --> 00:36:57.785
in terms of looking at

NOTE Confidence: 0.9804342

00:36:58.085 --> 00:36:59.384
combination of chemotherapy,

NOTE Confidence: 0.9941321

00:36:59.684 --> 00:37:00.984
radiation, and surgery.

NOTE Confidence: 0.75358367

00:37:01.710 --> 00:37:02.109
And,

NOTE Confidence: 0.9558782

00:37:02.510 --> 00:37:04.030
since the nineteen eighties, there

NOTE Confidence: 0.9558782

00:37:04.030 --> 00:37:05.790
have been many clinical trials

NOTE Confidence: 0.9558782

00:37:05.790 --> 00:37:06.770
looking at this,

NOTE Confidence: 0.9591956

00:37:07.230 --> 00:37:08.349
and this is all kind

NOTE Confidence: 0.9591956

00:37:08.349 --> 00:37:09.869
of put together in some

NOTE Confidence: 0.9591956

00:37:09.869 --> 00:37:11.550
nice meta analysis a few

NOTE Confidence: 0.9591956

00:37:11.550 --> 00:37:12.290
years ago,

NOTE Confidence: 0.9439774

00:37:13.070 --> 00:37:14.670
showing really, you know, kind

NOTE Confidence: 0.9439774

00:37:14.670 --> 00:37:15.905
of in this as we

NOTE Confidence: 0.9439774

00:37:15.905 --> 00:37:18.065
look down the this, the

NOTE Confidence: 0.9439774

00:37:18.065 --> 00:37:19.685
the unity line here that

NOTE Confidence: 0.9439774

00:37:19.825 --> 00:37:21.425
many of these trials with

NOTE Confidence: 0.9439774

00:37:21.425 --> 00:37:21.925
chemoradiation

NOTE Confidence: 0.92038345

00:37:22.705 --> 00:37:24.405
before rate, surgery

NOTE Confidence: 0.9687857

00:37:24.864 --> 00:37:26.705
suggest a benefit, but not

NOTE Confidence: 0.9687857

00:37:26.705 --> 00:37:29.364
necessarily a statistically significant benefit.

NOTE Confidence: 0.9687857

00:37:29.619 --> 00:37:30.540
But when you combine all

NOTE Confidence: 0.9687857

00:37:30.540 --> 00:37:32.180
of them together, there is

NOTE Confidence: 0.9687857

00:37:32.180 --> 00:37:34.599
something that suggests favoring chemoradiation

NOTE Confidence: 0.9925588

00:37:35.060 --> 00:37:36.520
for esophageal cancers.

NOTE Confidence: 0.9511579

00:37:36.900 --> 00:37:38.599
And very similarly, for chemotherapy

NOTE Confidence: 0.9511579

00:37:38.820 --> 00:37:39.719
without radiation,

NOTE Confidence: 0.9277053

00:37:40.739 --> 00:37:41.219
also,

NOTE Confidence: 0.9193794

00:37:41.540 --> 00:37:43.140
crossing unity. But then when

NOTE Confidence: 0.9193794

00:37:43.140 --> 00:37:44.359
you put them all together,

NOTE Confidence: 0.7760742

00:37:45.174 --> 00:37:46.234
potentially suggesting,

NOTE Confidence: 0.9674092

00:37:46.694 --> 00:37:48.214
although just touching unity,

NOTE Confidence: 0.97795504

00:37:48.614 --> 00:37:51.114
favoring chemotherapy. And so despite,

NOTE Confidence: 0.98826003

00:37:51.655 --> 00:37:52.694
I would say, maybe about

NOTE Confidence: 0.98826003

00:37:52.694 --> 00:37:54.214
twenty years of clinical trial

NOTE Confidence: 0.98826003

00:37:54.214 --> 00:37:54.714
work,

NOTE Confidence: 0.9342064

00:37:55.174 --> 00:37:56.555
the question still remained,

NOTE Confidence: 0.9798894

00:37:57.575 --> 00:37:59.120
really, you know, what what

NOTE Confidence: 0.9798894

00:37:59.280 --> 00:38:00.719
is it is anything better

NOTE Confidence: 0.9798894

00:38:00.719 --> 00:38:02.960
than surgery alone? And, this

NOTE Confidence: 0.9798894

00:38:02.960 --> 00:38:03.620
is where,

NOTE Confidence: 0.87326354

00:38:04.640 --> 00:38:06.739
the cross trial really,

NOTE Confidence: 0.998431

00:38:07.200 --> 00:38:07.700
changed

NOTE Confidence: 0.73964566

00:38:08.000 --> 00:38:08.900
was it was,

NOTE Confidence: 0.94054

00:38:09.280 --> 00:38:10.420
changed the paradigm,

NOTE Confidence: 0.9540043

00:38:10.800 --> 00:38:12.260
when it was published. And,

NOTE Confidence: 0.93443114

00:38:13.280 --> 00:38:15.065
and this is looking at,

NOTE Confidence: 0.93443114

00:38:15.385 --> 00:38:15.885
carboxyl

NOTE Confidence: 0.99076957

00:38:16.424 --> 00:38:16.924
chemotherapy

NOTE Confidence: 0.9990444

00:38:17.305 --> 00:38:17.964
with radiation

NOTE Confidence: 0.9782662

00:38:18.265 --> 00:38:19.244
prior to surgery,

NOTE Confidence: 0.93591636

00:38:19.864 --> 00:38:21.144
compared to surgery alone. And

NOTE Confidence: 0.93591636

00:38:21.144 --> 00:38:22.505
there was an overall survival

NOTE Confidence: 0.93591636

00:38:22.505 --> 00:38:23.005
benefit,

NOTE Confidence: 0.81718564

00:38:23.464 --> 00:38:25.005
using new adjuvant chemoradiation

NOTE Confidence: 0.88863987

00:38:25.785 --> 00:38:27.164
compared to surgery alone.

NOTE Confidence: 0.99396664

00:38:28.025 --> 00:38:29.700
When you break out squamous

NOTE Confidence: 0.99396664

00:38:29.700 --> 00:38:31.320
cell cancers and adenocarcinomas,

NOTE Confidence: 0.9906285

00:38:32.260 --> 00:38:32.760
really,

NOTE Confidence: 0.9663272

00:38:33.060 --> 00:38:34.980
it became very clear that

NOTE Confidence: 0.9663272

00:38:34.980 --> 00:38:36.660
the survival benefit for the

NOTE Confidence: 0.9663272

00:38:36.660 --> 00:38:38.340
CROS trial is really driven

NOTE Confidence: 0.9663272

00:38:38.340 --> 00:38:40.520
by, the squamous cell cancer

NOTE Confidence: 0.9663272

00:38:40.580 --> 00:38:42.420
subset and and not as

NOTE Confidence: 0.9663272

00:38:42.420 --> 00:38:43.640
much by the adenocarcinoma

NOTE Confidence: 0.9963119

00:38:45.094 --> 00:38:46.315
esophageal cancers.

NOTE Confidence: 0.9567976

00:38:47.335 --> 00:38:48.954
And, really interestingly,

NOTE Confidence: 0.9067021

00:38:49.654 --> 00:38:50.795
you know, carboxyl

NOTE Confidence: 0.95799625

00:38:51.575 --> 00:38:53.515
did not seem to affect,

NOTE Confidence: 0.99658513

00:38:54.055 --> 00:38:55.035
distant recurrence

NOTE Confidence: 0.9830616

00:38:55.414 --> 00:38:57.414
rates. That is, that even

NOTE Confidence: 0.9830616

00:38:57.414 --> 00:38:59.194
though this combination of chemotherapy

NOTE Confidence: 0.9684183

00:38:59.494 --> 00:38:59.994
radiation

NOTE Confidence: 0.9995074

00:39:00.375 --> 00:39:00.750
was

NOTE Confidence: 0.88127804

00:39:01.230 --> 00:39:01.730
better,

NOTE Confidence: 0.8810759

00:39:02.110 --> 00:39:04.690
at at reducing local regional

NOTE Confidence: 0.8810759

00:39:04.750 --> 00:39:05.250
recurrence,

NOTE Confidence: 0.9012535

00:39:06.270 --> 00:39:06.750
that,

NOTE Confidence: 0.97523874

00:39:07.630 --> 00:39:08.750
it it really didn't seem

NOTE Confidence: 0.97523874

00:39:08.750 --> 00:39:10.350
to decrease the rate of

NOTE Confidence: 0.97523874

00:39:10.350 --> 00:39:12.370
distant metastatic disease. So,

NOTE Confidence: 0.93356186

00:39:12.750 --> 00:39:14.430
ultimately, the conclusion from the

NOTE Confidence: 0.93356186

00:39:14.430 --> 00:39:15.250
CROS trial,

NOTE Confidence: 0.9563751

00:39:16.164 --> 00:39:17.645
my takeaway is that it

NOTE Confidence: 0.9563751

00:39:17.765 --> 00:39:19.385
it's a really good regimen

NOTE Confidence: 0.9563751

00:39:19.684 --> 00:39:21.545
probably for squamous cell cancers,

NOTE Confidence: 0.9989249

00:39:22.325 --> 00:39:23.924
but we probably can do

NOTE Confidence: 0.9989249

00:39:23.924 --> 00:39:25.305
better for adenocarcinomas.

NOTE Confidence: 0.9750802

00:39:27.605 --> 00:39:28.105
And

NOTE Confidence: 0.99273163

00:39:28.969 --> 00:39:29.930
there's been a lot of

NOTE Confidence: 0.99273163

00:39:29.930 --> 00:39:31.930
trials since then reported about

NOTE Confidence: 0.99273163

00:39:31.930 --> 00:39:32.910
effective chemotherapy

NOTE Confidence: 0.98968965

00:39:33.210 --> 00:39:33.950
for adenocarcinomas.

NOTE Confidence: 0.95302373

00:39:34.650 --> 00:39:36.829
And, looking at more

NOTE Confidence: 0.8715957

00:39:37.289 --> 00:39:37.789
aggressive

NOTE Confidence: 0.9989544

00:39:38.650 --> 00:39:39.150
chemotherapies,

NOTE Confidence: 0.9139224

00:39:40.890 --> 00:39:43.069
it does seem that chemotherapy

NOTE Confidence: 0.98036945

00:39:44.385 --> 00:39:45.825
may be equivalent or better

NOTE Confidence: 0.98036945

00:39:45.825 --> 00:39:46.565
than chemoradiation

NOTE Confidence: 0.9961568

00:39:47.025 --> 00:39:48.145
in the setting of surgical

NOTE Confidence: 0.9961568

00:39:48.145 --> 00:39:49.364
resections for adenocarcinomas.

NOTE Confidence: 0.9782527

00:39:49.825 --> 00:39:50.625
And I'm just going to

NOTE Confidence: 0.9782527

00:39:50.625 --> 00:39:51.745
focus on one of those

NOTE Confidence: 0.9782527

00:39:51.745 --> 00:39:53.505
trials, the ISOPEC trial, which

NOTE Confidence: 0.9782527

00:39:53.505 --> 00:39:54.325
made a big

NOTE Confidence: 0.93456566

00:39:55.105 --> 00:39:56.705
splash this year, very high

NOTE Confidence: 0.93456566

00:39:56.705 --> 00:39:58.860
impact, high profile publication.

NOTE Confidence: 0.9068372

00:39:59.800 --> 00:40:00.840
And, this,

NOTE Confidence: 0.9576851

00:40:01.400 --> 00:40:03.900
was run looking at randomizing

NOTE Confidence: 0.77799994

00:40:05.239 --> 00:40:05.739
perioperative

NOTE Confidence: 0.81196034

00:40:06.200 --> 00:40:07.100
FLOT chemotherapy,

NOTE Confidence: 0.92056715

00:40:08.200 --> 00:40:09.719
compared to the cross regimen

NOTE Confidence: 0.92056715

00:40:09.719 --> 00:40:10.605
of carboxyl

NOTE Confidence: 0.95658016

00:40:10.985 --> 00:40:12.045
and and radiation,

NOTE Confidence: 0.99887335

00:40:12.745 --> 00:40:13.565
for adenocarcinomas.

NOTE Confidence: 0.9617509

00:40:14.745 --> 00:40:17.065
And, it showed that the

NOTE Confidence: 0.9617509

00:40:17.065 --> 00:40:18.205
survival was improved

NOTE Confidence: 0.78997606

00:40:18.505 --> 00:40:18.905
with,

NOTE Confidence: 0.9902141

00:40:19.625 --> 00:40:20.125
perioperative

NOTE Confidence: 0.9996723

00:40:20.425 --> 00:40:20.925
chemotherapy

NOTE Confidence: 0.78782034

00:40:21.225 --> 00:40:21.725
flot,

NOTE Confidence: 0.95808756

00:40:22.185 --> 00:40:23.965
compared to the CROS regimen,

NOTE Confidence: 0.8909981

00:40:25.310 --> 00:40:27.230
with a really impressive five

NOTE Confidence: 0.8909981

00:40:27.230 --> 00:40:28.770
year overall survival rates.

NOTE Confidence: 0.97282887

00:40:29.070 --> 00:40:29.390
And,

NOTE Confidence: 0.92552495

00:40:29.870 --> 00:40:30.370
even,

NOTE Confidence: 0.9898635

00:40:30.910 --> 00:40:31.730
in adenocarcinomas,

NOTE Confidence: 0.8897419

00:40:33.150 --> 00:40:36.050
with, aggressive chemotherapy, FLOT regimen,

NOTE Confidence: 0.9797493

00:40:36.510 --> 00:40:38.830
an improved pathologic complete response

NOTE Confidence: 0.9797493

00:40:38.830 --> 00:40:40.215
rate compared to the CROS

NOTE Confidence: 0.9797493

00:40:40.295 --> 00:40:40.795
regimen.

NOTE Confidence: 0.9764259

00:40:41.495 --> 00:40:42.395
And so

NOTE Confidence: 0.9540929

00:40:42.695 --> 00:40:44.295
the ISOPEG trial really showed

NOTE Confidence: 0.9540929

00:40:44.295 --> 00:40:45.975
us, I think, that FLOT

NOTE Confidence: 0.9540929

00:40:45.975 --> 00:40:46.475
chemotherapy,

NOTE Confidence: 0.88911104

00:40:47.575 --> 00:40:48.075
is,

NOTE Confidence: 0.951824

00:40:48.455 --> 00:40:50.935
really the appropriate regimen for,

NOTE Confidence: 0.99916965

00:40:51.255 --> 00:40:52.395
esophageal adenocarcinomas

NOTE Confidence: 0.8362315

00:40:53.335 --> 00:40:55.250
and, probably more effective in

NOTE Confidence: 0.8362315

00:40:55.250 --> 00:40:55.750
carboxyl.

NOTE Confidence: 0.93477803

00:40:57.250 --> 00:40:58.770
The question though is is

NOTE Confidence: 0.93477803

00:40:58.770 --> 00:41:00.150
really this idea

NOTE Confidence: 0.94548684

00:41:00.450 --> 00:41:02.390
of with more effective chemotherapy,

NOTE Confidence: 0.9141725

00:41:03.489 --> 00:41:04.469
you know, can,

NOTE Confidence: 0.9984503

00:41:05.410 --> 00:41:05.910
radiation

NOTE Confidence: 0.9993931

00:41:06.290 --> 00:41:07.270
still add

NOTE Confidence: 0.93956137

00:41:08.855 --> 00:41:10.214
to to to the benefit

NOTE Confidence: 0.93956137

00:41:10.214 --> 00:41:12.555
of neoadjuvant therapy before surgery

NOTE Confidence: 0.8386874

00:41:13.734 --> 00:41:15.755
when you're using FLOT chemotherapy

NOTE Confidence: 0.8386874

00:41:15.895 --> 00:41:16.875
instead of carboxyl

NOTE Confidence: 0.653569

00:41:17.575 --> 00:41:18.075
chemotherapy?

NOTE Confidence: 0.94067365

00:41:19.255 --> 00:41:20.935
And, this is a little

NOTE Confidence: 0.94067365

00:41:20.935 --> 00:41:22.055
bit of an older trial,

NOTE Confidence: 0.94067365

00:41:22.055 --> 00:41:22.555
but

NOTE Confidence: 0.95892406

00:41:23.550 --> 00:41:25.330
I like this trial because

NOTE Confidence: 0.95892406

00:41:25.390 --> 00:41:26.930
this trial kinda compared

NOTE Confidence: 0.928161

00:41:27.469 --> 00:41:28.370
in a,

NOTE Confidence: 0.8803042

00:41:28.989 --> 00:41:30.050
roundabout way,

NOTE Confidence: 0.9896265

00:41:31.070 --> 00:41:31.390
chemo

NOTE Confidence: 0.8389592

00:41:31.870 --> 00:41:32.930
FOLFOX chemotherapy

NOTE Confidence: 0.7327613

00:41:33.469 --> 00:41:34.210
to carboxyl,

NOTE Confidence: 0.9522022

00:41:34.989 --> 00:41:37.330
both with, radiation treatment.

NOTE Confidence: 0.9711281

00:41:37.835 --> 00:41:39.934
And this is a, adaptive

NOTE Confidence: 0.9361513

00:41:40.234 --> 00:41:42.494
trial. So patients were randomized

NOTE Confidence: 0.9361513

00:41:42.714 --> 00:41:44.974
to either FOLFOX or cobrataxol.

NOTE Confidence: 0.990111

00:41:45.594 --> 00:41:46.815
And then if they responded

NOTE Confidence: 0.990111

00:41:46.875 --> 00:41:47.994
to one or the other

NOTE Confidence: 0.990111

00:41:47.994 --> 00:41:48.494
chemotherapy,

NOTE Confidence: 0.99396664

00:41:49.674 --> 00:41:51.434
they then continued on that

NOTE Confidence: 0.99396664

00:41:51.434 --> 00:41:51.934
chemotherapy

NOTE Confidence: 0.805387

00:41:52.795 --> 00:41:53.219
with,

NOTE Confidence: 0.99530375

00:41:53.700 --> 00:41:55.780
radiation. If they were resistant

NOTE Confidence: 0.99530375

00:41:55.780 --> 00:41:57.380
to that chemotherapy, they actually

NOTE Confidence: 0.99530375

00:41:57.380 --> 00:41:58.840
switched over to the other

NOTE Confidence: 0.99530375

00:41:58.980 --> 00:42:00.739
type of chemotherapy together with

NOTE Confidence: 0.99530375

00:42:00.739 --> 00:42:01.239
radiation.

NOTE Confidence: 0.923828

00:42:01.940 --> 00:42:03.540
And, the five year old

NOTE Confidence: 0.923828

00:42:03.540 --> 00:42:05.460
overall survival here was about

NOTE Confidence: 0.923828

00:42:05.460 --> 00:42:06.739
fifty three percent. This is

NOTE Confidence: 0.923828

00:42:06.739 --> 00:42:08.359
a phase two trial randomized

NOTE Confidence: 0.923828

00:42:08.420 --> 00:42:09.825
trial, so a smaller trial

NOTE Confidence: 0.923828

00:42:09.825 --> 00:42:11.585
than than, or phase three

NOTE Confidence: 0.923828

00:42:11.585 --> 00:42:12.645
trial. But still,

NOTE Confidence: 0.9190451

00:42:13.105 --> 00:42:14.625
five year overall survival of

NOTE Confidence: 0.9190451

00:42:14.625 --> 00:42:16.225
fifty three page percent, which

NOTE Confidence: 0.9190451

00:42:16.225 --> 00:42:17.744
is about similar to the

NOTE Confidence: 0.9190451

00:42:17.744 --> 00:42:19.344
winning arm of isopec. And

NOTE Confidence: 0.9190451

00:42:19.344 --> 00:42:21.605
then also the PCR rates

NOTE Confidence: 0.9591317

00:42:22.059 --> 00:42:24.079
for the, folks who responded

NOTE Confidence: 0.9591317

00:42:24.140 --> 00:42:25.520
to FOLFOX chemotherapy

NOTE Confidence: 0.89428324

00:42:25.980 --> 00:42:28.000
was, significantly higher,

NOTE Confidence: 0.9991979

00:42:28.779 --> 00:42:30.160
at twenty six percent.

NOTE Confidence: 0.9897013

00:42:30.859 --> 00:42:32.239
So, you know,

NOTE Confidence: 0.94706815

00:42:32.700 --> 00:42:34.344
I I think that, again,

NOTE Confidence: 0.94706815

00:42:34.344 --> 00:42:35.625
this is kind of comparing

NOTE Confidence: 0.94706815

00:42:35.625 --> 00:42:36.905
two trials, which you're not

NOTE Confidence: 0.94706815

00:42:36.905 --> 00:42:38.585
really supposed to do. But,

NOTE Confidence: 0.94706815

00:42:38.825 --> 00:42:39.864
you know, it kinda gives

NOTE Confidence: 0.94706815

00:42:39.864 --> 00:42:41.225
you a a suggestion that

NOTE Confidence: 0.94706815

00:42:41.225 --> 00:42:41.725
maybe

NOTE Confidence: 0.9001851

00:42:42.185 --> 00:42:44.025
FOLFOX based or five f

NOTE Confidence: 0.9001851

00:42:44.025 --> 00:42:45.945
u based, excuse me, multi

NOTE Confidence: 0.9001851

00:42:45.945 --> 00:42:46.844
agent chemotherapy

NOTE Confidence: 0.87881356

00:42:49.250 --> 00:42:50.290
is the way to go

NOTE Confidence: 0.87881356

00:42:50.290 --> 00:42:51.670
with a favorable

NOTE Confidence: 0.9991643

00:42:51.969 --> 00:42:53.430
five year overall survival

NOTE Confidence: 0.84817034

00:42:54.130 --> 00:42:55.809
and, that the path CR

NOTE Confidence: 0.84817034

00:42:55.809 --> 00:42:56.290
rate,

NOTE Confidence: 0.8298259

00:42:56.609 --> 00:42:57.349
may be

NOTE Confidence: 0.9998503

00:42:57.650 --> 00:42:58.150
improved

NOTE Confidence: 0.88608426

00:42:58.609 --> 00:43:00.210
still even in the setting

NOTE Confidence: 0.88608426

00:43:00.210 --> 00:43:02.050
of five of even five

NOTE Confidence: 0.88608426

00:43:02.050 --> 00:43:03.190
of few based chemotherapy,

NOTE Confidence: 0.9381008

00:43:03.890 --> 00:43:05.315
you know, with with a

NOTE Confidence: 0.9381008

00:43:05.315 --> 00:43:07.234
more favorable path CR rate

NOTE Confidence: 0.9381008

00:43:07.234 --> 00:43:08.694
with the addition of radiation.

NOTE Confidence: 0.9449672

00:43:09.795 --> 00:43:11.174
And where this is important

NOTE Confidence: 0.9449672

00:43:11.234 --> 00:43:13.094
is is really this idea

NOTE Confidence: 0.9449672

00:43:13.315 --> 00:43:13.714
that,

NOTE Confidence: 0.9506056

00:43:14.835 --> 00:43:17.075
doctor Boffa just really, went

NOTE Confidence: 0.9506056

00:43:17.075 --> 00:43:18.114
through in a lot of

NOTE Confidence: 0.9506056

00:43:18.114 --> 00:43:19.234
detail, which is that there's

NOTE Confidence: 0.9506056

00:43:19.234 --> 00:43:20.780
this kind of attractive

NOTE Confidence: 0.8911786

00:43:22.840 --> 00:43:24.360
concept of saying, okay. For

NOTE Confidence: 0.8911786

00:43:24.360 --> 00:43:26.040
folks who have a complete

NOTE Confidence: 0.8911786

00:43:26.040 --> 00:43:27.480
pathologic risk or a complete

NOTE Confidence: 0.8911786

00:43:27.480 --> 00:43:29.020
clinical response to chemoradiation,

NOTE Confidence: 0.9958804

00:43:29.719 --> 00:43:30.940
can we avoid surgery?

NOTE Confidence: 0.9499997

00:43:31.560 --> 00:43:33.320
And, so the SANSO trial

NOTE Confidence: 0.9499997

00:43:33.320 --> 00:43:34.575
is one example of that

NOTE Confidence: 0.9499997

00:43:34.655 --> 00:43:36.275
trial. There's others.

NOTE Confidence: 0.8661986

00:43:36.974 --> 00:43:37.454
And,

NOTE Confidence: 0.99396837

00:43:37.775 --> 00:43:40.015
interestingly enough, you know, they

NOTE Confidence: 0.99396837

00:43:40.015 --> 00:43:41.135
did look at the global

NOTE Confidence: 0.99396837

00:43:41.135 --> 00:43:42.114
quality of life,

NOTE Confidence: 0.99792457

00:43:42.575 --> 00:43:43.954
in the Sano trial,

NOTE Confidence: 0.9342499

00:43:44.494 --> 00:43:45.855
which did improve in the

NOTE Confidence: 0.9342499

00:43:45.855 --> 00:43:47.535
short term, but, seemed to

NOTE Confidence: 0.9342499

00:43:47.535 --> 00:43:48.239
level out

NOTE Confidence: 0.9368196

00:43:48.800 --> 00:43:49.920
in the long term. And

NOTE Confidence: 0.9368196

00:43:49.920 --> 00:43:50.719
so that was kind of

NOTE Confidence: 0.9368196

00:43:50.719 --> 00:43:52.260
an interesting finding where,

NOTE Confidence: 0.9724949

00:43:52.719 --> 00:43:54.239
despite patients really,

NOTE Confidence: 0.81598324

00:43:54.640 --> 00:43:55.140
probably,

NOTE Confidence: 0.99848974

00:43:55.600 --> 00:43:56.100
preferring

NOTE Confidence: 0.79077375

00:43:56.880 --> 00:43:57.540
to avoid

NOTE Confidence: 0.72875416

00:43:57.840 --> 00:43:58.340
surgery

NOTE Confidence: 0.9593627

00:43:58.960 --> 00:44:00.400
that, their quality of life

NOTE Confidence: 0.9593627

00:44:00.400 --> 00:44:02.160
may actually improve given enough

NOTE Confidence: 0.9593627

00:44:02.160 --> 00:44:03.219
time after surgery.

NOTE Confidence: 0.9968358

00:44:03.655 --> 00:44:05.175
And, you know, speaking of

NOTE Confidence: 0.9968358

00:44:05.175 --> 00:44:06.075
quality of life,

NOTE Confidence: 0.91181624

00:44:06.535 --> 00:44:07.815
this has been looked at

NOTE Confidence: 0.91181624

00:44:07.815 --> 00:44:09.195
out of from the Netherlands.

NOTE Confidence: 0.91181624

00:44:09.255 --> 00:44:09.755
And,

NOTE Confidence: 0.99128366

00:44:10.055 --> 00:44:10.855
you know, I think the

NOTE Confidence: 0.99128366

00:44:10.855 --> 00:44:12.635
idea here is that with

NOTE Confidence: 0.99128366

00:44:12.855 --> 00:44:13.355
chemoradiation

NOTE Confidence: 0.97385454

00:44:16.250 --> 00:44:17.530
across the board, maybe about

NOTE Confidence: 0.97385454

00:44:17.530 --> 00:44:19.469
twenty to thirty percent pathologic

NOTE Confidence: 0.97385454

00:44:19.530 --> 00:44:21.450
complete response rates across most

NOTE Confidence: 0.97385454

00:44:21.450 --> 00:44:21.950
studies.

NOTE Confidence: 0.9802397

00:44:22.650 --> 00:44:23.150
That

NOTE Confidence: 0.62139475

00:44:23.930 --> 00:44:24.089
the

NOTE Confidence: 0.9680446

00:44:24.730 --> 00:44:26.089
again, the holy grail is

NOTE Confidence: 0.9680446

00:44:26.089 --> 00:44:27.210
really to try to figure

NOTE Confidence: 0.9680446

00:44:27.210 --> 00:44:29.049
out, is there any way

NOTE Confidence: 0.9680446

00:44:29.049 --> 00:44:30.989
that we can, really accurately

NOTE Confidence: 0.9680446

00:44:31.130 --> 00:44:33.535
assess pathologic complete response rates?

NOTE Confidence: 0.98131603

00:44:33.914 --> 00:44:34.795
Is there any way that

NOTE Confidence: 0.98131603

00:44:34.795 --> 00:44:35.454
we can,

NOTE Confidence: 0.9859411

00:44:35.994 --> 00:44:37.755
increase the the number of

NOTE Confidence: 0.9859411

00:44:37.755 --> 00:44:39.454
patients that achieve this pathologic

NOTE Confidence: 0.9859411

00:44:39.674 --> 00:44:41.214
complete response rate? But,

NOTE Confidence: 0.9994976

00:44:41.515 --> 00:44:43.454
this is a nice demonstration

NOTE Confidence: 0.96696454

00:44:43.914 --> 00:44:46.015
that patients prefer organ preservation.

NOTE Confidence: 0.9518907

00:44:47.130 --> 00:44:48.170
You know? And, actually, they

NOTE Confidence: 0.9518907

00:44:48.170 --> 00:44:49.930
considered organ preservation as the

NOTE Confidence: 0.9518907

00:44:49.930 --> 00:44:52.010
second most important factor after

NOTE Confidence: 0.9518907

00:44:52.010 --> 00:44:53.069
overall survival

NOTE Confidence: 0.94783676

00:44:53.529 --> 00:44:55.289
and, even would accept a

NOTE Confidence: 0.94783676

00:44:55.289 --> 00:44:56.829
a trade off in survival

NOTE Confidence: 0.94783676

00:44:56.969 --> 00:44:59.049
for significant probability of organ

NOTE Confidence: 0.94783676

00:44:59.049 --> 00:45:01.085
preservation. And so, again, this

NOTE Confidence: 0.94783676

00:45:01.085 --> 00:45:02.605
is something where there's a

NOTE Confidence: 0.94783676

00:45:02.605 --> 00:45:03.904
real need here

NOTE Confidence: 0.9997561

00:45:04.605 --> 00:45:05.265
to improve

NOTE Confidence: 0.90912575

00:45:05.565 --> 00:45:06.944
our results with chemoradiation,

NOTE Confidence: 0.9720071

00:45:08.045 --> 00:45:09.085
and and try to make

NOTE Confidence: 0.9720071

00:45:09.085 --> 00:45:11.265
this a more realistic feasible

NOTE Confidence: 0.9996958

00:45:11.724 --> 00:45:12.864
option for patients.

NOTE Confidence: 0.81606925

00:45:13.964 --> 00:45:14.464
So,

NOTE Confidence: 0.9953497

00:45:15.164 --> 00:45:15.984
in summary,

NOTE Confidence: 0.9397381

00:45:16.340 --> 00:45:18.020
just the Yale approach to

NOTE Confidence: 0.9397381

00:45:18.020 --> 00:45:18.520
chemoradiation,

NOTE Confidence: 0.87805617

00:45:19.140 --> 00:45:20.260
you know, based on off

NOTE Confidence: 0.87805617

00:45:20.260 --> 00:45:21.160
the CROS trial,

NOTE Confidence: 0.97957426

00:45:22.260 --> 00:45:24.180
the squamous cell cancers really

NOTE Confidence: 0.97957426

00:45:24.180 --> 00:45:26.100
had the, the best outcomes

NOTE Confidence: 0.97957426

00:45:26.100 --> 00:45:27.000
there of any

NOTE Confidence: 0.7793524

00:45:27.620 --> 00:45:28.120
preoperative,

NOTE Confidence: 0.9366701

00:45:28.980 --> 00:45:30.920
trial for squamous cells. So,

NOTE Confidence: 0.8917355

00:45:31.585 --> 00:45:33.585
squamous cell cancers, we're following

NOTE Confidence: 0.8917355

00:45:33.585 --> 00:45:34.705
at this point the cross

NOTE Confidence: 0.8917355

00:45:34.705 --> 00:45:35.205
regimen.

NOTE Confidence: 0.9959903

00:45:35.825 --> 00:45:36.725
For adenocarcinomas,

NOTE Confidence: 0.9851182

00:45:37.905 --> 00:45:39.364
it's clear that FLOT chemotherapy

NOTE Confidence: 0.92035335

00:45:39.825 --> 00:45:41.505
is is probably the best

NOTE Confidence: 0.92035335

00:45:41.505 --> 00:45:42.005
chemotherapy

NOTE Confidence: 0.7949929

00:45:42.864 --> 00:45:43.364
regimen.

NOTE Confidence: 0.98588216

00:45:43.710 --> 00:45:45.230
And, we may actually add

NOTE Confidence: 0.98588216

00:45:45.230 --> 00:45:45.890
in radiation,

NOTE Confidence: 0.9850485

00:45:46.670 --> 00:45:47.950
on top of that depending

NOTE Confidence: 0.9850485

00:45:47.950 --> 00:45:48.450
on,

NOTE Confidence: 0.9096054

00:45:49.469 --> 00:45:51.250
on on certain risk factors.

NOTE Confidence: 0.9887194

00:45:51.790 --> 00:45:53.790
So patients who are at

NOTE Confidence: 0.9887194

00:45:53.790 --> 00:45:54.910
high risk who are high

NOTE Confidence: 0.9887194

00:45:54.910 --> 00:45:56.915
risk surgical candidates, who are,

NOTE Confidence: 0.9887194

00:45:57.155 --> 00:45:58.755
maybe unlikely to ever get

NOTE Confidence: 0.9887194

00:45:58.755 --> 00:46:00.375
to surgery because of comorbidities

NOTE Confidence: 0.9502031

00:46:01.155 --> 00:46:03.415
or, or or age or,

NOTE Confidence: 0.9401237

00:46:04.435 --> 00:46:06.135
high risk of metastatic disease.

NOTE Confidence: 0.9754576

00:46:06.594 --> 00:46:07.555
You know, these are probably

NOTE Confidence: 0.9754576

00:46:07.555 --> 00:46:08.614
patients that,

NOTE Confidence: 0.96699786

00:46:09.315 --> 00:46:11.094
may be better served with

NOTE Confidence: 0.96699786

00:46:11.100 --> 00:46:11.600
chemoradiation,

NOTE Confidence: 0.98268384

00:46:13.020 --> 00:46:14.540
bulky cancers where there may

NOTE Confidence: 0.98268384

00:46:14.540 --> 00:46:15.660
be a risk of positive

NOTE Confidence: 0.98268384

00:46:15.660 --> 00:46:16.880
margins with surgery,

NOTE Confidence: 0.9887628

00:46:17.180 --> 00:46:18.400
and extensive lymphadenopathy

NOTE Confidence: 0.99238116

00:46:18.700 --> 00:46:19.980
where radiation may help to

NOTE Confidence: 0.99238116

00:46:19.980 --> 00:46:20.780
cover the,

NOTE Confidence: 0.99918246

00:46:21.180 --> 00:46:22.080
nodal basins.

NOTE Confidence: 0.9898069

00:46:23.915 --> 00:46:25.435
And then as a as

NOTE Confidence: 0.9898069

00:46:25.435 --> 00:46:26.494
a as a final

NOTE Confidence: 0.9706682

00:46:27.114 --> 00:46:27.855
two minute,

NOTE Confidence: 0.86490154

00:46:28.474 --> 00:46:29.695
one minute, two minute,

NOTE Confidence: 0.82174426

00:46:33.114 --> 00:46:33.994
notes that,

NOTE Confidence: 0.96234876

00:46:34.635 --> 00:46:36.075
you know, at Yale, we

NOTE Confidence: 0.96234876

00:46:36.075 --> 00:46:37.135
do have some,

NOTE Confidence: 0.9950271

00:46:37.835 --> 00:46:39.420
newer things coming down the

NOTE Confidence: 0.9950271

00:46:39.420 --> 00:46:41.200
line for esophageal cancer.

NOTE Confidence: 0.97730553

00:46:42.219 --> 00:46:42.700
And,

NOTE Confidence: 0.88187665

00:46:43.020 --> 00:46:44.160
one approach which,

NOTE Confidence: 0.9975353

00:46:44.619 --> 00:46:45.520
again, is

NOTE Confidence: 0.976645

00:46:45.980 --> 00:46:47.420
getting more traction is this

NOTE Confidence: 0.976645

00:46:47.420 --> 00:46:48.400
idea of treating,

NOTE Confidence: 0.99880594

00:46:49.260 --> 00:46:50.960
limited metastatic disease

NOTE Confidence: 0.9995471

00:46:51.339 --> 00:46:52.239
with curative

NOTE Confidence: 0.88875633

00:46:52.540 --> 00:46:53.599
intent. And,

NOTE Confidence: 0.9995634

00:46:54.085 --> 00:46:54.585
this

NOTE Confidence: 0.8493693

00:46:54.885 --> 00:46:55.925
is this is,

NOTE Confidence: 0.9381765

00:46:56.645 --> 00:46:58.245
the SABRE COMET trial, which

NOTE Confidence: 0.9381765

00:46:58.245 --> 00:46:59.225
looked at metastatic

NOTE Confidence: 0.8916459

00:46:59.844 --> 00:47:00.745
cancer patients,

NOTE Confidence: 0.9778697

00:47:01.205 --> 00:47:02.645
a small trial, one to

NOTE Confidence: 0.9778697

00:47:02.645 --> 00:47:04.025
five metastatic lesions,

NOTE Confidence: 0.85576504

00:47:04.805 --> 00:47:06.505
with standard of care,

NOTE Confidence: 0.9925134

00:47:07.205 --> 00:47:07.705
palliation

NOTE Confidence: 0.9889931

00:47:08.245 --> 00:47:08.745
versus

NOTE Confidence: 0.95234907

00:47:09.730 --> 00:47:11.110
standard of care with,

NOTE Confidence: 0.9986895

00:47:11.890 --> 00:47:12.390
SBRT

NOTE Confidence: 0.94764006

00:47:12.690 --> 00:47:14.230
showing a survival benefit,

NOTE Confidence: 0.9418633

00:47:15.010 --> 00:47:16.370
with the addition of local

NOTE Confidence: 0.9418633

00:47:16.370 --> 00:47:18.610
therapy with high dose ablative

NOTE Confidence: 0.9418633

00:47:18.610 --> 00:47:19.110
radiation.

NOTE Confidence: 0.72842324

00:47:20.130 --> 00:47:20.630
And,

NOTE Confidence: 0.9626008

00:47:21.825 --> 00:47:23.285
a series from MD Anderson

NOTE Confidence: 0.9626008

00:47:23.505 --> 00:47:24.325
for esophageal

NOTE Confidence: 0.94660807

00:47:24.625 --> 00:47:26.224
gastric cancers looking at a

NOTE Confidence: 0.94660807

00:47:26.224 --> 00:47:27.125
similar concept,

NOTE Confidence: 0.9390966

00:47:27.744 --> 00:47:29.585
patients getting systemic therapy with

NOTE Confidence: 0.9390966

00:47:29.585 --> 00:47:30.645
an excellent response,

NOTE Confidence: 0.9372527

00:47:31.025 --> 00:47:32.864
and then consolidation surgery or

NOTE Confidence: 0.9372527

00:47:32.864 --> 00:47:35.049
radiation. And, you know, kind

NOTE Confidence: 0.9372527

00:47:35.049 --> 00:47:35.630
of intriguingly,

NOTE Confidence: 0.97067064

00:47:36.489 --> 00:47:37.790
even up to,

NOTE Confidence: 0.9791163

00:47:38.329 --> 00:47:39.069
ten years,

NOTE Confidence: 0.9672538

00:47:39.530 --> 00:47:41.130
about a twenty percent survival

NOTE Confidence: 0.9672538

00:47:41.130 --> 00:47:42.430
in this highly selected

NOTE Confidence: 0.98868394

00:47:42.730 --> 00:47:43.549
single institution

NOTE Confidence: 0.95250726

00:47:44.010 --> 00:47:45.150
retrospective study.

NOTE Confidence: 0.9644006

00:47:45.690 --> 00:47:47.705
But, certainly suggested that maybe

NOTE Confidence: 0.9644006

00:47:47.705 --> 00:47:48.985
in some patients, there can

NOTE Confidence: 0.9644006

00:47:48.985 --> 00:47:50.285
be long term survival

NOTE Confidence: 0.855969

00:47:50.745 --> 00:47:51.965
with, consolidative,

NOTE Confidence: 0.99963933

00:47:52.665 --> 00:47:53.165
radiation.

NOTE Confidence: 0.98396295

00:47:53.945 --> 00:47:55.625
And so at Yale, we

NOTE Confidence: 0.98396295

00:47:55.625 --> 00:47:56.765
have this trial,

NOTE Confidence: 0.87950796

00:47:57.145 --> 00:47:57.545
through,

NOTE Confidence: 0.99679554

00:47:58.025 --> 00:47:59.405
open at this point,

NOTE Confidence: 0.9531354

00:48:00.105 --> 00:48:01.225
which is open through the

NOTE Confidence: 0.9531354

00:48:01.225 --> 00:48:03.200
ECOG group, looking at this

NOTE Confidence: 0.9531354

00:48:03.200 --> 00:48:05.359
concept of consolidative radiation in

NOTE Confidence: 0.9531354

00:48:05.359 --> 00:48:06.579
patients with oligometastatic

NOTE Confidence: 0.9596157

00:48:07.039 --> 00:48:09.039
HER2 negative esophageal or gastric

NOTE Confidence: 0.9596157

00:48:09.039 --> 00:48:09.539
cancer,

NOTE Confidence: 0.99782974

00:48:10.239 --> 00:48:11.839
patients with less than five

NOTE Confidence: 0.99782974

00:48:11.839 --> 00:48:12.980
metastatic lesions,

NOTE Confidence: 0.97337437

00:48:13.680 --> 00:48:15.219
and at least stable disease

NOTE Confidence: 0.97337437

00:48:15.440 --> 00:48:17.295
with first line systemic therapy

NOTE Confidence: 0.97337437

00:48:17.295 --> 00:48:18.355
and then continuing

NOTE Confidence: 0.84900224

00:48:18.655 --> 00:48:19.475
on to,

NOTE Confidence: 0.9968764

00:48:20.494 --> 00:48:21.775
radiation treatment to all of

NOTE Confidence: 0.9968764

00:48:21.775 --> 00:48:23.075
the metastatic sites.

NOTE Confidence: 0.99302024

00:48:23.535 --> 00:48:23.935
And,

NOTE Confidence: 0.9633246

00:48:24.734 --> 00:48:25.855
you know, we're this is,

NOTE Confidence: 0.9633246

00:48:26.015 --> 00:48:26.755
this is

NOTE Confidence: 0.92221904

00:48:27.775 --> 00:48:29.855
an international trial and open

NOTE Confidence: 0.92221904

00:48:29.855 --> 00:48:30.994
now for enrollment.

NOTE Confidence: 0.9930917

00:48:31.710 --> 00:48:33.550
And then, finally, just because,

NOTE Confidence: 0.9930917

00:48:33.869 --> 00:48:34.770
you can't have

NOTE Confidence: 0.91244775

00:48:35.310 --> 00:48:37.230
radiation a radiation talk without

NOTE Confidence: 0.91244775

00:48:37.230 --> 00:48:38.850
some something with new technology,

NOTE Confidence: 0.9272599

00:48:40.270 --> 00:48:41.170
just a

NOTE Confidence: 0.79571176

00:48:41.790 --> 00:48:42.530
note that

NOTE Confidence: 0.97292423

00:48:43.835 --> 00:48:45.674
that Yale is is going

NOTE Confidence: 0.97292423

00:48:45.674 --> 00:48:47.515
to be opening Connecticut's first

NOTE Confidence: 0.97292423

00:48:47.515 --> 00:48:48.575
proton center,

NOTE Confidence: 0.960035

00:48:48.875 --> 00:48:49.994
and this should be opening

NOTE Confidence: 0.960035

00:48:49.994 --> 00:48:51.434
up toward the end of,

NOTE Confidence: 0.960035

00:48:51.755 --> 00:48:52.575
next year,

NOTE Confidence: 0.98526716

00:48:53.594 --> 00:48:55.055
in Wallingford, Connecticut.

NOTE Confidence: 0.94157076

00:48:55.835 --> 00:48:58.094
And, protons are really attractive,

NOTE Confidence: 0.99609137

00:48:59.040 --> 00:48:59.540
and,

NOTE Confidence: 0.9851756

00:49:00.080 --> 00:49:02.020
you know, cutting edge radiation

NOTE Confidence: 0.9761925

00:49:02.320 --> 00:49:02.820
technology.

NOTE Confidence: 0.95481396

00:49:04.000 --> 00:49:05.700
And the advantage of protons

NOTE Confidence: 0.95481396

00:49:05.840 --> 00:49:07.840
is that, where X rays

NOTE Confidence: 0.95481396

00:49:07.840 --> 00:49:09.040
go through your body and

NOTE Confidence: 0.95481396

00:49:09.040 --> 00:49:10.575
no matter how carefully we

NOTE Confidence: 0.96230197

00:49:11.295 --> 00:49:11.795
aim,

NOTE Confidence: 0.99298996

00:49:12.335 --> 00:49:14.114
x rays at the esophagus,

NOTE Confidence: 0.99298996

00:49:14.175 --> 00:49:15.614
there's always this low dose

NOTE Confidence: 0.99298996

00:49:15.614 --> 00:49:17.295
spread of radiation to the

NOTE Confidence: 0.99298996

00:49:17.295 --> 00:49:18.355
lungs and heart,

NOTE Confidence: 0.9691226

00:49:18.974 --> 00:49:19.795
that protons,

NOTE Confidence: 0.9941583

00:49:20.415 --> 00:49:21.454
stop. And so,

NOTE Confidence: 0.9808959

00:49:21.855 --> 00:49:23.214
you can see in this

NOTE Confidence: 0.9808959

00:49:23.214 --> 00:49:24.655
example of a proton plan

NOTE Confidence: 0.9808959

00:49:24.655 --> 00:49:25.990
delivering dose to the rate

NOTE Confidence: 0.9808959

00:49:26.070 --> 00:49:27.750
to the to the primary

NOTE Confidence: 0.9808959

00:49:27.750 --> 00:49:28.250
tumor,

NOTE Confidence: 0.9509959

00:49:28.630 --> 00:49:29.830
but really sparing a lot

NOTE Confidence: 0.9509959

00:49:29.830 --> 00:49:31.430
more lung from this low

NOTE Confidence: 0.9509959

00:49:31.430 --> 00:49:33.190
dose and very importantly, sparing

NOTE Confidence: 0.9509959

00:49:33.190 --> 00:49:34.310
a lot more hearts. And

NOTE Confidence: 0.9509959

00:49:34.310 --> 00:49:35.290
we know that,

NOTE Confidence: 0.8658671

00:49:35.989 --> 00:49:37.610
survival is actually improved,

NOTE Confidence: 0.9412799

00:49:38.230 --> 00:49:39.830
the the less heart dose

NOTE Confidence: 0.9412799

00:49:39.830 --> 00:49:42.094
we we, we deliver. And,

NOTE Confidence: 0.9938836

00:49:42.575 --> 00:49:43.614
that that's a that's a

NOTE Confidence: 0.9938836

00:49:43.614 --> 00:49:45.714
big risk with esophageal cancer.

NOTE Confidence: 0.9075751

00:49:46.414 --> 00:49:46.914
So,

NOTE Confidence: 0.95534045

00:49:48.414 --> 00:49:50.094
this is, something we're looking

NOTE Confidence: 0.95534045

00:49:50.094 --> 00:49:51.694
forward to and and, again,

NOTE Confidence: 0.95534045

00:49:51.694 --> 00:49:53.075
will be a big benefit,

NOTE Confidence: 0.9995609

00:49:53.535 --> 00:49:54.655
you know, for our patients

NOTE Confidence: 0.9995609

00:49:54.655 --> 00:49:55.635
here in Connecticut.

NOTE Confidence: 0.991416

00:49:56.289 --> 00:49:58.069
So, thank you. I apologize

NOTE Confidence: 0.991416

00:49:58.130 --> 00:49:58.950
for going

NOTE Confidence: 0.92443836

00:49:59.250 --> 00:50:00.230
over, and,

NOTE Confidence: 0.99913955

00:50:00.849 --> 00:50:01.349
I'll

NOTE Confidence: 0.88176525

00:50:01.650 --> 00:50:02.950
turn it back to,

NOTE Confidence: 0.9891441

00:50:03.969 --> 00:50:04.869
doctor Sundar.

NOTE Confidence: 0.9573423

00:50:06.930 --> 00:50:08.609
Thanks. Thanks, Kevin. That was

NOTE Confidence: 0.9573423

00:50:08.609 --> 00:50:09.890
really fantastic, and,

NOTE Confidence: 0.98529834

00:50:10.625 --> 00:50:11.744
looking forward to having a

NOTE Confidence: 0.98529834

00:50:11.744 --> 00:50:12.244
multidisciplinary,

NOTE Confidence: 0.9932763

00:50:13.184 --> 00:50:14.385
discussion on some of the

NOTE Confidence: 0.9932763

00:50:14.385 --> 00:50:14.885
cases,

NOTE Confidence: 0.99805945

00:50:15.585 --> 00:50:16.325
after this.

NOTE Confidence: 0.9803079

00:50:16.704 --> 00:50:18.405
I'm gonna give the last,

NOTE Confidence: 0.83652663

00:50:19.265 --> 00:50:20.325
planned talk.

NOTE Confidence: 0.82190824

00:50:30.400 --> 00:50:30.880
Right.

NOTE Confidence: 0.97419715

00:50:31.440 --> 00:50:32.559
And so for the last

NOTE Confidence: 0.97419715

00:50:32.559 --> 00:50:33.780
part, I'm gonna cover,

NOTE Confidence: 0.9721829

00:50:34.239 --> 00:50:34.739
updates,

NOTE Confidence: 0.9903134

00:50:35.040 --> 00:50:36.239
over the last year in

NOTE Confidence: 0.9903134

00:50:36.239 --> 00:50:37.219
systemic therapies,

NOTE Confidence: 0.95631534

00:50:38.094 --> 00:50:39.695
mainly covering the three main

NOTE Confidence: 0.95631534

00:50:39.695 --> 00:50:42.195
components of, HER2 targeted therapies,

NOTE Confidence: 0.90724325

00:50:42.975 --> 00:50:44.495
as Doctor. Gibson talked about,

NOTE Confidence: 0.90724325

00:50:44.495 --> 00:50:46.335
GLAADIN eighteen point two, as

NOTE Confidence: 0.90724325

00:50:46.335 --> 00:50:48.335
well as, some immunotherapy updates

NOTE Confidence: 0.90724325

00:50:48.335 --> 00:50:48.995
as well.

NOTE Confidence: 0.98564124

00:50:50.880 --> 00:50:51.760
And this has been one

NOTE Confidence: 0.98564124

00:50:51.760 --> 00:50:53.040
of the most exciting aspects

NOTE Confidence: 0.98564124

00:50:53.040 --> 00:50:53.780
of gastroesophageal

NOTE Confidence: 0.96461153

00:50:54.160 --> 00:50:55.680
cancers is that in terms

NOTE Confidence: 0.96461153

00:50:55.680 --> 00:50:57.780
of just putative therapeutic targets,

NOTE Confidence: 0.96461153

00:50:57.920 --> 00:50:59.119
we can see that this

NOTE Confidence: 0.96461153

00:50:59.119 --> 00:51:00.579
entire space has really

NOTE Confidence: 0.95629174

00:51:01.200 --> 00:51:02.480
exploded over the past few

NOTE Confidence: 0.95629174

00:51:02.480 --> 00:51:04.295
years. We have multiple different

NOTE Confidence: 0.95629174

00:51:04.295 --> 00:51:05.494
drugs that are coming into

NOTE Confidence: 0.95629174

00:51:05.494 --> 00:51:06.315
the space. And

NOTE Confidence: 0.98106235

00:51:06.614 --> 00:51:07.114
by,

NOTE Confidence: 0.99849856

00:51:07.654 --> 00:51:08.154
improving

NOTE Confidence: 0.96599114

00:51:08.614 --> 00:51:10.055
systemic control as well as

NOTE Confidence: 0.96599114

00:51:10.055 --> 00:51:11.994
response rates to primary tumors,

NOTE Confidence: 0.96599114

00:51:12.135 --> 00:51:13.674
the idea is in combination,

NOTE Confidence: 0.96599114

00:51:13.734 --> 00:51:14.694
as you can see, with

NOTE Confidence: 0.96599114

00:51:14.694 --> 00:51:16.234
radiation as well as surgery,

NOTE Confidence: 0.96599114

00:51:16.370 --> 00:51:17.330
the goal is to try

NOTE Confidence: 0.96599114

00:51:17.330 --> 00:51:18.710
and be able to cure

NOTE Confidence: 0.96599114

00:51:18.850 --> 00:51:20.210
a lot much larger number

NOTE Confidence: 0.96599114

00:51:20.210 --> 00:51:21.810
of patients who are suffering

NOTE Confidence: 0.96599114

00:51:21.810 --> 00:51:22.550
from gastroesophageal

NOTE Confidence: 0.9992427

00:51:22.930 --> 00:51:24.050
cancer than what we could

NOTE Confidence: 0.9992427

00:51:24.050 --> 00:51:24.870
in the past.

NOTE Confidence: 0.97868985

00:51:28.050 --> 00:51:29.330
So in the HER2 space,

NOTE Confidence: 0.97868985

00:51:29.330 --> 00:51:30.230
we know that,

NOTE Confidence: 0.99926186

00:51:30.770 --> 00:51:31.830
the data from

NOTE Confidence: 0.90038526

00:51:32.424 --> 00:51:34.025
keynote eight eleven, which looked

NOTE Confidence: 0.90038526

00:51:34.025 --> 00:51:35.484
at patients with,

NOTE Confidence: 0.96393615

00:51:35.944 --> 00:51:37.565
advanced unresectable gastrosophageal

NOTE Confidence: 0.9775046

00:51:38.105 --> 00:51:40.285
cancers that were HER2 positive,

NOTE Confidence: 0.964901

00:51:41.385 --> 00:51:43.145
newly diagnosed. And upfront, they

NOTE Confidence: 0.964901

00:51:43.145 --> 00:51:43.885
were randomized

NOTE Confidence: 0.9993036

00:51:44.265 --> 00:51:45.885
to receive either chemotherapy

NOTE Confidence: 0.92428267

00:51:46.480 --> 00:51:48.239
in combination of trastuzumab, which

NOTE Confidence: 0.92428267

00:51:48.239 --> 00:51:49.620
has been the Toga regimen,

NOTE Confidence: 0.92428267

00:51:49.840 --> 00:51:50.880
which we have been giving

NOTE Confidence: 0.92428267

00:51:50.880 --> 00:51:52.480
patients for the past ten

NOTE Confidence: 0.92428267

00:51:52.480 --> 00:51:53.300
plus years,

NOTE Confidence: 0.99646544

00:51:54.160 --> 00:51:55.460
to also then receive

NOTE Confidence: 0.9927233

00:51:56.560 --> 00:51:57.060
pembrolizumab.

NOTE Confidence: 0.9865925

00:51:57.760 --> 00:51:59.120
And this trial had early

NOTE Confidence: 0.9865925

00:51:59.120 --> 00:52:00.160
results that read out a

NOTE Confidence: 0.9865925

00:52:00.160 --> 00:52:02.025
couple of years ago. And,

NOTE Confidence: 0.99744034

00:52:02.965 --> 00:52:04.085
we know that there was

NOTE Confidence: 0.99744034

00:52:04.085 --> 00:52:06.025
a progression free survival benefit

NOTE Confidence: 0.99744034

00:52:06.244 --> 00:52:07.705
for the addition of pembrolizumab

NOTE Confidence: 0.93552923

00:52:08.565 --> 00:52:10.085
to the Toga regimen with

NOTE Confidence: 0.93552923

00:52:10.085 --> 00:52:11.305
chemotherapy and trastuzumab.

NOTE Confidence: 0.97189486

00:52:11.765 --> 00:52:12.805
And this has been now

NOTE Confidence: 0.97189486

00:52:12.805 --> 00:52:14.440
the standard of care for

NOTE Confidence: 0.97189486

00:52:14.440 --> 00:52:16.280
patients over the past couple

NOTE Confidence: 0.97189486

00:52:16.280 --> 00:52:17.560
of years, where if you're

NOTE Confidence: 0.97189486

00:52:17.560 --> 00:52:18.380
HER2 positive,

NOTE Confidence: 0.9356334

00:52:18.840 --> 00:52:19.980
the addition of pembrolizumab,

NOTE Confidence: 0.9121219

00:52:20.920 --> 00:52:23.100
has demonstrated survival benefit.

NOTE Confidence: 0.9892447

00:52:23.400 --> 00:52:25.080
Last year, we actually saw

NOTE Confidence: 0.9892447

00:52:25.080 --> 00:52:26.219
the overall survival,

NOTE Confidence: 0.91660345

00:52:26.680 --> 00:52:28.440
results that was presented by

NOTE Confidence: 0.91660345

00:52:28.440 --> 00:52:30.505
Doctor Janjie Guyan and, also

NOTE Confidence: 0.91660345

00:52:30.505 --> 00:52:31.545
published in the New England

NOTE Confidence: 0.91660345

00:52:31.545 --> 00:52:33.305
Journal of Medicine. And there

NOTE Confidence: 0.91660345

00:52:33.305 --> 00:52:34.445
continues to be

NOTE Confidence: 0.9721156

00:52:34.825 --> 00:52:36.425
a clear separation of the

NOTE Confidence: 0.9721156

00:52:36.425 --> 00:52:38.105
curves and a survival benefit

NOTE Confidence: 0.9721156

00:52:38.105 --> 00:52:39.405
for the addition of pembrolizumab.

NOTE Confidence: 0.94251144

00:52:41.065 --> 00:52:42.460
This is the long one

NOTE Confidence: 0.94251144

00:52:42.460 --> 00:52:44.080
of the longest overall survivals

NOTE Confidence: 0.94251144

00:52:44.140 --> 00:52:45.980
we've seen at twenty months

NOTE Confidence: 0.94251144

00:52:45.980 --> 00:52:47.600
for patients who received pembrolizumab

NOTE Confidence: 0.95997924

00:52:48.140 --> 00:52:49.580
compared to sixteen point eight

NOTE Confidence: 0.95997924

00:52:49.580 --> 00:52:50.860
months for those that received

NOTE Confidence: 0.95997924

00:52:50.860 --> 00:52:51.360
placebo

NOTE Confidence: 0.8626291

00:52:51.660 --> 00:52:52.860
with a very nice hazard

NOTE Confidence: 0.8626291

00:52:52.860 --> 00:52:54.560
ratio zero point eight zero.

NOTE Confidence: 0.92759347

00:52:54.860 --> 00:52:55.260
And,

NOTE Confidence: 0.9924702

00:52:56.495 --> 00:52:57.614
however, one of the things

NOTE Confidence: 0.9924702

00:52:57.614 --> 00:52:59.075
to note about this trial

NOTE Confidence: 0.9924702

00:52:59.295 --> 00:53:00.435
is the fact that,

NOTE Confidence: 0.99860126

00:53:01.135 --> 00:53:02.435
there was clearly a

NOTE Confidence: 0.9993474

00:53:02.735 --> 00:53:03.795
lack of benefit

NOTE Confidence: 0.97346634

00:53:04.175 --> 00:53:05.555
of the addition of pembrolizumab

NOTE Confidence: 0.97346634

00:53:05.775 --> 00:53:06.975
for those that had a

NOTE Confidence: 0.97346634

00:53:06.975 --> 00:53:07.875
PD L1,

NOTE Confidence: 0.97605836

00:53:08.415 --> 00:53:09.775
CPS score of less than

NOTE Confidence: 0.97605836

00:53:09.775 --> 00:53:11.369
one. And in this group

NOTE Confidence: 0.97605836

00:53:11.369 --> 00:53:12.430
of patients, actually,

NOTE Confidence: 0.9715288

00:53:12.730 --> 00:53:14.349
the survival was poorer

NOTE Confidence: 0.9271481

00:53:14.650 --> 00:53:16.089
for the patients that received

NOTE Confidence: 0.9271481

00:53:16.089 --> 00:53:18.329
the pembrolizumab con considered compared

NOTE Confidence: 0.9271481

00:53:18.329 --> 00:53:19.770
to standard of care, and

NOTE Confidence: 0.9271481

00:53:19.770 --> 00:53:20.969
that led the FDA to

NOTE Confidence: 0.9271481

00:53:20.969 --> 00:53:21.950
actually update

NOTE Confidence: 0.9854532

00:53:23.075 --> 00:53:24.275
the indication for the role

NOTE Confidence: 0.9854532

00:53:24.275 --> 00:53:24.855
of pembrolizumab

NOTE Confidence: 0.87365323

00:53:25.315 --> 00:53:27.555
and restricted only to patients

NOTE Confidence: 0.87365323

00:53:27.555 --> 00:53:29.815
that are tumors that had,

NOTE Confidence: 0.9274899

00:53:30.515 --> 00:53:32.114
both a co expression of

NOTE Confidence: 0.9274899

00:53:32.114 --> 00:53:33.974
HER2 as well as PDL1.

NOTE Confidence: 0.9297818

00:53:34.619 --> 00:53:36.140
And so now in terms

NOTE Confidence: 0.9297818

00:53:36.140 --> 00:53:36.960
of the HER2,

NOTE Confidence: 0.988716

00:53:37.500 --> 00:53:38.480
positive gastroesophageal

NOTE Confidence: 0.97619605

00:53:39.019 --> 00:53:39.519
cancers,

NOTE Confidence: 0.6417427

00:53:40.700 --> 00:53:41.359
and gastroesophageal

NOTE Confidence: 0.9683005

00:53:41.739 --> 00:53:42.239
adenocarcinomas

NOTE Confidence: 0.9160629

00:53:42.859 --> 00:53:44.880
for frontline treatment, the recommendation

NOTE Confidence: 0.9160629

00:53:45.099 --> 00:53:46.460
is in combination with the

NOTE Confidence: 0.9160629

00:53:46.460 --> 00:53:47.680
platinum and fluoropyrimidine

NOTE Confidence: 0.94371504

00:53:48.460 --> 00:53:49.755
doublet is to look at

NOTE Confidence: 0.94371504

00:53:49.755 --> 00:53:51.755
the PDL one score. And

NOTE Confidence: 0.94371504

00:53:51.755 --> 00:53:53.275
the PDL one CPS is

NOTE Confidence: 0.94371504

00:53:53.275 --> 00:53:54.954
less than one, then the

NOTE Confidence: 0.94371504

00:53:54.954 --> 00:53:56.155
recommendation is only for the

NOTE Confidence: 0.94371504

00:53:56.155 --> 00:53:57.135
addition of trastuzumab.

NOTE Confidence: 0.98226714

00:53:57.755 --> 00:53:58.795
But if the PDL one

NOTE Confidence: 0.98226714

00:53:58.795 --> 00:54:00.335
CPS is one or greater,

NOTE Confidence: 0.98226714

00:54:00.474 --> 00:54:01.835
then the recommendation is to

NOTE Confidence: 0.98226714

00:54:01.835 --> 00:54:02.895
add trastuzumab

NOTE Confidence: 0.965136

00:54:03.275 --> 00:54:04.555
with a PD one blockade

NOTE Confidence: 0.965136

00:54:04.555 --> 00:54:05.510
with pembrolizumab,

NOTE Confidence: 0.9791344

00:54:05.969 --> 00:54:07.570
and that's kind of what

NOTE Confidence: 0.9791344

00:54:07.570 --> 00:54:09.250
we now follow as a

NOTE Confidence: 0.9791344

00:54:09.250 --> 00:54:10.690
standard of care for HER2

NOTE Confidence: 0.9791344

00:54:10.690 --> 00:54:11.670
positive gastroesophageal

NOTE Confidence: 0.9969052

00:54:12.130 --> 00:54:12.630
cancers.

NOTE Confidence: 0.9682605

00:54:15.410 --> 00:54:16.850
Switching gears a little bit,

NOTE Confidence: 0.9682605

00:54:16.850 --> 00:54:18.310
we know that, trastuzumab

NOTE Confidence: 0.8999248

00:54:18.610 --> 00:54:20.705
deruxtecan, which is antibody drug

NOTE Confidence: 0.8999248

00:54:20.705 --> 00:54:21.205
conjugate,

NOTE Confidence: 0.6719125

00:54:22.225 --> 00:54:23.445
before two HER2,

NOTE Confidence: 0.99586713

00:54:23.825 --> 00:54:24.325
demonstrated

NOTE Confidence: 0.83484435

00:54:24.945 --> 00:54:26.085
a survival benefit

NOTE Confidence: 0.9334021

00:54:26.385 --> 00:54:27.285
compared to,

NOTE Confidence: 0.9217951

00:54:27.825 --> 00:54:29.665
physician's choice of chemotherapy in

NOTE Confidence: 0.9217951

00:54:29.665 --> 00:54:31.105
the Destiny Gastric o one

NOTE Confidence: 0.9217951

00:54:31.105 --> 00:54:31.605
study.

NOTE Confidence: 0.9943581

00:54:31.985 --> 00:54:33.265
And this actually led to

NOTE Confidence: 0.9943581

00:54:33.265 --> 00:54:33.925
the approval

NOTE Confidence: 0.89251024

00:54:34.329 --> 00:54:35.790
of trastuzumab, deruxtecan

NOTE Confidence: 0.8112163

00:54:36.170 --> 00:54:36.670
about,

NOTE Confidence: 0.99858975

00:54:37.609 --> 00:54:38.910
four years ago now

NOTE Confidence: 0.93608594

00:54:39.250 --> 00:54:39.750
for,

NOTE Confidence: 0.9945266

00:54:40.650 --> 00:54:42.410
patients that had progressed on

NOTE Confidence: 0.9945266

00:54:42.410 --> 00:54:44.510
frontline treatment with trastuzumab

NOTE Confidence: 0.7071789

00:54:45.450 --> 00:54:45.950
and,

NOTE Confidence: 0.9898162

00:54:46.569 --> 00:54:47.069
then

NOTE Confidence: 0.94289774

00:54:48.355 --> 00:54:50.215
were treated with trastuzumab deruxtecan,

NOTE Confidence: 0.94289774

00:54:50.355 --> 00:54:51.555
which is the antibody drug

NOTE Confidence: 0.94289774

00:54:51.555 --> 00:54:52.055
conjugate.

NOTE Confidence: 0.9190724

00:54:54.995 --> 00:54:56.595
The the initial data that

NOTE Confidence: 0.9190724

00:54:56.595 --> 00:54:58.595
was presented in, Destiny Gastric

NOTE Confidence: 0.9190724

00:54:58.595 --> 00:55:00.435
o one was purely generated

NOTE Confidence: 0.9190724

00:55:00.435 --> 00:55:02.114
from an Asian study. And

NOTE Confidence: 0.9190724

00:55:02.114 --> 00:55:03.540
this is why we had

NOTE Confidence: 0.9190724

00:55:03.540 --> 00:55:04.900
the SNE gastric o four

NOTE Confidence: 0.9190724

00:55:04.900 --> 00:55:06.980
study that, was a randomized

NOTE Confidence: 0.9190724

00:55:06.980 --> 00:55:08.900
phase three trial, specifically in

NOTE Confidence: 0.9190724

00:55:08.900 --> 00:55:10.840
the second line setting for,

NOTE Confidence: 0.9296732

00:55:11.620 --> 00:55:13.380
patients that have progressed on

NOTE Confidence: 0.9296732

00:55:13.380 --> 00:55:15.000
frontline treatment with trazuzumab

NOTE Confidence: 0.974752

00:55:15.380 --> 00:55:15.880
based,

NOTE Confidence: 0.9953038

00:55:16.260 --> 00:55:16.760
treatments.

NOTE Confidence: 0.9971636

00:55:17.060 --> 00:55:17.560
And

NOTE Confidence: 0.92216015

00:55:17.955 --> 00:55:19.795
importantly in this study, all

NOTE Confidence: 0.92216015

00:55:19.795 --> 00:55:21.175
patients had a rebiopsy

NOTE Confidence: 0.9859956

00:55:21.635 --> 00:55:22.135
of

NOTE Confidence: 0.958673

00:55:22.435 --> 00:55:24.755
the tumors and confirmed HER2

NOTE Confidence: 0.958673

00:55:24.755 --> 00:55:26.614
positivity before they were randomized.

NOTE Confidence: 0.99025834

00:55:26.995 --> 00:55:28.355
And they were randomized to

NOTE Confidence: 0.99025834

00:55:28.355 --> 00:55:29.495
receive either trastuzumab,

NOTE Confidence: 0.63302934

00:55:29.795 --> 00:55:30.295
duraxtecan,

NOTE Confidence: 0.99102247

00:55:30.755 --> 00:55:31.735
or paclitaxel

NOTE Confidence: 0.8059999

00:55:32.114 --> 00:55:32.935
and ramosirumab.

NOTE Confidence: 0.8766024

00:55:33.930 --> 00:55:34.430
And,

NOTE Confidence: 0.9860861

00:55:36.170 --> 00:55:37.369
this actually had a press

NOTE Confidence: 0.9860861

00:55:37.369 --> 00:55:39.369
release that announced that this

NOTE Confidence: 0.9860861

00:55:39.369 --> 00:55:41.069
study met its primary endpoint

NOTE Confidence: 0.9860861

00:55:41.210 --> 00:55:42.910
for overall survival, suggesting

NOTE Confidence: 0.80450004

00:55:44.170 --> 00:55:45.849
that trastuzumab, durax deacon has

NOTE Confidence: 0.80450004

00:55:45.849 --> 00:55:46.910
not did

NOTE Confidence: 0.9590916

00:55:47.755 --> 00:55:49.594
demonstrate an overall survival benefit

NOTE Confidence: 0.9590916

00:55:49.594 --> 00:55:51.135
over paclitaxel and ramosirumab,

NOTE Confidence: 0.9397551

00:55:51.675 --> 00:55:52.715
and this is actually going

NOTE Confidence: 0.9397551

00:55:52.715 --> 00:55:53.535
to be presented,

NOTE Confidence: 0.9885849

00:55:53.994 --> 00:55:55.355
as an oral abstract at

NOTE Confidence: 0.9885849

00:55:55.355 --> 00:55:56.715
ASCO in a couple of

NOTE Confidence: 0.9885849

00:55:56.715 --> 00:55:57.215
months.

NOTE Confidence: 0.9349797

00:55:58.235 --> 00:55:59.275
And we're looking forward to

NOTE Confidence: 0.9349797

00:55:59.275 --> 00:56:00.549
hear these data, and this

NOTE Confidence: 0.9349797

00:56:00.549 --> 00:56:01.289
will be practice

NOTE Confidence: 0.9693277

00:56:01.670 --> 00:56:03.190
reaffirming in the United States

NOTE Confidence: 0.9693277

00:56:03.190 --> 00:56:04.630
where we are very often

NOTE Confidence: 0.9693277

00:56:04.630 --> 00:56:07.109
using trastuzumab, deruxtecan. In second

NOTE Confidence: 0.9693277

00:56:07.109 --> 00:56:08.150
line, one of the take

NOTE Confidence: 0.9693277

00:56:08.150 --> 00:56:09.510
home messages from this trial

NOTE Confidence: 0.9693277

00:56:09.510 --> 00:56:10.250
would be,

NOTE Confidence: 0.9880244

00:56:10.630 --> 00:56:12.170
the the concept of potentially

NOTE Confidence: 0.9880244

00:56:12.309 --> 00:56:13.210
looking to rebiopsy

NOTE Confidence: 0.98104364

00:56:13.510 --> 00:56:15.145
patients and confirm the HER2

NOTE Confidence: 0.98104364

00:56:15.145 --> 00:56:15.645
positivity

NOTE Confidence: 0.9738075

00:56:15.945 --> 00:56:18.025
status before treating these patients

NOTE Confidence: 0.9738075

00:56:18.025 --> 00:56:18.525
with,

NOTE Confidence: 0.9944374

00:56:18.825 --> 00:56:20.445
another HER2 targeted therapy.

NOTE Confidence: 0.9264663

00:56:22.345 --> 00:56:23.705
We also saw very early

NOTE Confidence: 0.9264663

00:56:23.705 --> 00:56:25.565
data from Destiny Gastric O3

NOTE Confidence: 0.9264663

00:56:25.625 --> 00:56:26.585
where they were trying to

NOTE Confidence: 0.9264663

00:56:26.585 --> 00:56:27.965
bring trastuzumab deruxtecan

NOTE Confidence: 0.83325326

00:56:28.265 --> 00:56:29.085
into frontline

NOTE Confidence: 0.92954254

00:56:29.500 --> 00:56:31.020
in combination with five,

NOTE Confidence: 0.8570735

00:56:31.340 --> 00:56:32.480
five FU chemotherapy

NOTE Confidence: 0.9882964

00:56:33.260 --> 00:56:34.160
and pembrolizumab.

NOTE Confidence: 0.98089135

00:56:35.180 --> 00:56:35.680
And,

NOTE Confidence: 0.98614997

00:56:36.460 --> 00:56:38.000
these data were actually presented,

NOTE Confidence: 0.85616887

00:56:38.380 --> 00:56:40.219
late last year, by doctor

NOTE Confidence: 0.85616887

00:56:40.219 --> 00:56:41.180
Janjigin at,

NOTE Confidence: 0.9106867

00:56:41.660 --> 00:56:42.160
ESMO,

NOTE Confidence: 0.97771674

00:56:42.540 --> 00:56:44.060
where there was actually very

NOTE Confidence: 0.97771674

00:56:44.060 --> 00:56:44.560
promising,

NOTE Confidence: 0.96164936

00:56:45.465 --> 00:56:47.145
waterfall plots that we saw

NOTE Confidence: 0.96164936

00:56:47.145 --> 00:56:48.605
of the combination of trastuzumab,

NOTE Confidence: 0.96164936

00:56:48.825 --> 00:56:49.325
daroxetecan

NOTE Confidence: 0.86582977

00:56:49.785 --> 00:56:51.864
with chemotherapy with five f

NOTE Confidence: 0.86582977

00:56:51.864 --> 00:56:53.005
u and pembrolizumab.

NOTE Confidence: 0.99844897

00:56:53.625 --> 00:56:54.685
And you can see,

NOTE Confidence: 0.99701744

00:56:55.065 --> 00:56:56.745
almost all the patients responded

NOTE Confidence: 0.99701744

00:56:56.745 --> 00:56:58.525
to treatment with a progression

NOTE Confidence: 0.99701744

00:56:58.585 --> 00:56:59.945
free survival of about ten

NOTE Confidence: 0.99701744

00:56:59.945 --> 00:57:00.445
months.

NOTE Confidence: 0.99912626

00:57:01.020 --> 00:57:02.320
One of the concerns about

NOTE Confidence: 0.82965326

00:57:02.620 --> 00:57:03.820
the ethnic gastric o three

NOTE Confidence: 0.82965326

00:57:03.820 --> 00:57:04.320
was,

NOTE Confidence: 0.9446842

00:57:04.860 --> 00:57:06.400
the higher dose of trastuzumab

NOTE Confidence: 0.9446842

00:57:06.620 --> 00:57:08.140
derazecan with six point four

NOTE Confidence: 0.9446842

00:57:08.140 --> 00:57:10.060
milligrams per kilogram actually had

NOTE Confidence: 0.9446842

00:57:10.060 --> 00:57:11.520
quite a lot of toxicities.

NOTE Confidence: 0.9860489

00:57:11.980 --> 00:57:13.420
And so they actually opened

NOTE Confidence: 0.9860489

00:57:13.420 --> 00:57:15.234
a second cohort with a

NOTE Confidence: 0.9860489

00:57:15.234 --> 00:57:16.355
lower dose of five point

NOTE Confidence: 0.9860489

00:57:16.355 --> 00:57:17.795
four milligrams per kilogram of,

NOTE Confidence: 0.751405

00:57:18.435 --> 00:57:19.655
atrazuzumab deruxtecan.

NOTE Confidence: 0.97348523

00:57:20.115 --> 00:57:21.815
And this had very similar

NOTE Confidence: 0.97348523

00:57:21.875 --> 00:57:23.075
sort of response rates and

NOTE Confidence: 0.97348523

00:57:23.075 --> 00:57:23.575
survival,

NOTE Confidence: 0.98967

00:57:23.875 --> 00:57:25.395
but had much, much lower

NOTE Confidence: 0.98967

00:57:25.395 --> 00:57:25.895
toxicities.

NOTE Confidence: 0.9688569

00:57:26.675 --> 00:57:27.875
And this is what has

NOTE Confidence: 0.9688569

00:57:27.875 --> 00:57:29.820
now translated into the DESTINY

NOTE Confidence: 0.9688569

00:57:29.820 --> 00:57:31.740
gastric o five trial, which

NOTE Confidence: 0.9688569

00:57:31.740 --> 00:57:33.900
is looking at frontline HER2

NOTE Confidence: 0.9688569

00:57:33.900 --> 00:57:36.240
positive gastric cancer and randomizing

NOTE Confidence: 0.9688569

00:57:36.300 --> 00:57:38.240
patients to receive TDXD

NOTE Confidence: 0.918596

00:57:38.780 --> 00:57:40.000
chemotherapy and pembrolizumab

NOTE Confidence: 0.92214674

00:57:40.700 --> 00:57:42.380
versus the toga versus the

NOTE Confidence: 0.92214674

00:57:42.380 --> 00:57:44.505
keynote eight eleven regimen with,

NOTE Confidence: 0.92214674

00:57:44.984 --> 00:57:45.484
chemotherapy,

NOTE Confidence: 0.9640145

00:57:45.865 --> 00:57:47.164
trastuzumab, and pembrolizumab.

NOTE Confidence: 0.9387101

00:57:48.345 --> 00:57:49.545
And this trial is actually

NOTE Confidence: 0.9387101

00:57:49.545 --> 00:57:51.005
opening at Yale very soon.

NOTE Confidence: 0.9255125

00:57:54.105 --> 00:57:56.345
Next, switching gears. Doctor Gibson

NOTE Confidence: 0.9255125

00:57:56.345 --> 00:57:57.865
spoke about claudine eighteen point

NOTE Confidence: 0.9255125

00:57:57.865 --> 00:57:58.260
two.

NOTE Confidence: 0.96573013

00:57:58.740 --> 00:58:00.340
This is a normal protein

NOTE Confidence: 0.96573013

00:58:00.340 --> 00:58:02.420
that's expressed, tight junction protein

NOTE Confidence: 0.96573013

00:58:02.420 --> 00:58:03.480
that's seen in,

NOTE Confidence: 0.9578125

00:58:04.020 --> 00:58:05.400
normal gastric mucosa.

NOTE Confidence: 0.99091977

00:58:05.780 --> 00:58:06.280
But,

NOTE Confidence: 0.9640464

00:58:07.220 --> 00:58:08.660
in cancer cells, the the

NOTE Confidence: 0.9640464

00:58:08.660 --> 00:58:10.180
the claudin eighteen the tumor

NOTE Confidence: 0.9640464

00:58:10.180 --> 00:58:11.640
cells lose the polarity

NOTE Confidence: 0.96101385

00:58:12.035 --> 00:58:13.335
that leads to an overexpression

NOTE Confidence: 0.96101385

00:58:13.475 --> 00:58:14.755
of claudin eighteen point two

NOTE Confidence: 0.96101385

00:58:14.755 --> 00:58:15.415
on surface,

NOTE Confidence: 0.97334146

00:58:15.715 --> 00:58:16.455
and zolbituximab

NOTE Confidence: 0.9969059

00:58:16.835 --> 00:58:18.435
is a monoclonal antibody that

NOTE Confidence: 0.9969059

00:58:18.435 --> 00:58:19.875
binds to claudin eighteen point

NOTE Confidence: 0.9969059

00:58:19.875 --> 00:58:20.375
two.

NOTE Confidence: 0.97220194

00:58:22.435 --> 00:58:23.555
A couple of years ago

NOTE Confidence: 0.97220194

00:58:23.555 --> 00:58:24.950
now, we saw,

NOTE Confidence: 0.959265

00:58:25.330 --> 00:58:27.090
two randomized phase three trials,

NOTE Confidence: 0.959265

00:58:27.090 --> 00:58:28.710
the SPOTLIGHT and GLO trials.

NOTE Confidence: 0.959265

00:58:28.930 --> 00:58:30.050
Both trials looked at the

NOTE Confidence: 0.959265

00:58:30.050 --> 00:58:31.270
combination of chemotherapy.

NOTE Confidence: 0.9808459

00:58:31.890 --> 00:58:33.349
SPOTLIGHT looked at FOLFOX,

NOTE Confidence: 0.98714536

00:58:33.810 --> 00:58:34.310
while,

NOTE Confidence: 0.9391488

00:58:34.770 --> 00:58:36.070
GLO looked at KPOXX

NOTE Confidence: 0.94105256

00:58:36.575 --> 00:58:37.715
with or without zolpidemap

NOTE Confidence: 0.97839934

00:58:38.335 --> 00:58:39.855
in patients that had an

NOTE Confidence: 0.97839934

00:58:39.855 --> 00:58:41.695
overexpression of claudine eighteen point

NOTE Confidence: 0.97839934

00:58:41.695 --> 00:58:43.695
two, which doctor Gibson explained

NOTE Confidence: 0.97839934

00:58:43.695 --> 00:58:44.975
was in more than seventy

NOTE Confidence: 0.97839934

00:58:44.975 --> 00:58:46.015
five percent of the tumor

NOTE Confidence: 0.97839934

00:58:46.015 --> 00:58:47.795
cells. And in both trials,

NOTE Confidence: 0.983256

00:58:48.895 --> 00:58:50.355
there was an overall survival

NOTE Confidence: 0.983256

00:58:50.415 --> 00:58:51.780
benefit for the addition of

NOTE Confidence: 0.983256

00:58:51.780 --> 00:58:52.280
zolpituximab

NOTE Confidence: 0.71050566

00:58:52.740 --> 00:58:53.400
two chemotherapy

NOTE Confidence: 0.9262026

00:58:54.100 --> 00:58:55.780
with an overall survival benefit

NOTE Confidence: 0.9262026

00:58:55.780 --> 00:58:57.220
improvement of about three months

NOTE Confidence: 0.9262026

00:58:57.220 --> 00:58:58.420
in both trials and a

NOTE Confidence: 0.9262026

00:58:58.420 --> 00:58:59.700
hazards ratio of zero point

NOTE Confidence: 0.9262026

00:58:59.700 --> 00:59:00.520
seven five.

NOTE Confidence: 0.97930723

00:59:00.820 --> 00:59:01.780
There was also a very

NOTE Confidence: 0.97930723

00:59:01.780 --> 00:59:03.540
clear improvement in progression free

NOTE Confidence: 0.97930723

00:59:03.540 --> 00:59:05.220
survival that was matched on

NOTE Confidence: 0.97930723

00:59:05.220 --> 00:59:06.885
both trials. And this led

NOTE Confidence: 0.97930723

00:59:06.885 --> 00:59:08.665
to the approval of zolbituximab

NOTE Confidence: 0.9811585

00:59:09.365 --> 00:59:09.865
in,

NOTE Confidence: 0.97349006

00:59:10.405 --> 00:59:12.085
the United States. The FDA

NOTE Confidence: 0.97349006

00:59:12.085 --> 00:59:13.445
approved it in October last

NOTE Confidence: 0.97349006

00:59:13.445 --> 00:59:14.665
year. And so,

NOTE Confidence: 0.980831

00:59:15.205 --> 00:59:16.245
most patients that have an

NOTE Confidence: 0.980831

00:59:16.245 --> 00:59:17.845
expression of claudoin eighteen point

NOTE Confidence: 0.980831

00:59:17.845 --> 00:59:19.385
two can be offered zolbituximab

NOTE Confidence: 0.99548495

00:59:19.845 --> 00:59:21.145
in combination with chemotherapy.

NOTE Confidence: 0.97507364

00:59:23.849 --> 00:59:25.690
Interestingly, in both trials, there

NOTE Confidence: 0.97507364

00:59:25.690 --> 00:59:27.390
was no improvement in objective

NOTE Confidence: 0.97507364

00:59:27.450 --> 00:59:28.890
response rates to the addition

NOTE Confidence: 0.97507364

00:59:28.890 --> 00:59:29.470
of zolpidemab.

NOTE Confidence: 0.9415065

00:59:29.770 --> 00:59:30.809
So although there was a

NOTE Confidence: 0.9415065

00:59:30.809 --> 00:59:33.050
survival improvement, there was no

NOTE Confidence: 0.9415065

00:59:33.050 --> 00:59:34.829
objective response rate improvement,

NOTE Confidence: 0.8547376

00:59:35.530 --> 00:59:36.030
with,

NOTE Confidence: 0.9295767

00:59:36.494 --> 00:59:37.295
in as you can see

NOTE Confidence: 0.9295767

00:59:37.295 --> 00:59:38.575
in spotlight, it was sixty

NOTE Confidence: 0.9295767

00:59:38.575 --> 00:59:39.795
point seven in the zolbituximab

NOTE Confidence: 0.84288245

00:59:40.095 --> 00:59:41.474
arm and sixty two

NOTE Confidence: 0.9973839

00:59:41.855 --> 00:59:43.795
percent in the placebo arm.

NOTE Confidence: 0.9875892

00:59:45.375 --> 00:59:47.134
One of the problems with,

NOTE Confidence: 0.9875892

00:59:47.535 --> 00:59:48.035
zolbituximab

NOTE Confidence: 0.98872113

00:59:48.770 --> 00:59:49.670
is that because

NOTE Confidence: 0.9658399

00:59:50.130 --> 00:59:51.410
the claudine eighteen point two

NOTE Confidence: 0.9658399

00:59:51.410 --> 00:59:52.690
is expressed in the normal

NOTE Confidence: 0.9658399

00:59:52.690 --> 00:59:53.589
gastric mucosa

NOTE Confidence: 0.9724057

00:59:53.890 --> 00:59:55.250
is that there is quite

NOTE Confidence: 0.9724057

00:59:55.250 --> 00:59:56.530
a lot of nausea and

NOTE Confidence: 0.9724057

00:59:56.530 --> 00:59:58.390
vomiting that these patients express,

NOTE Confidence: 0.97883725

00:59:58.849 --> 01:00:00.690
these patients face, and the

NOTE Confidence: 0.97883725

01:00:00.690 --> 01:00:02.130
nausea and vomiting is very

NOTE Confidence: 0.97883725

01:00:02.130 --> 01:00:02.630
often

NOTE Confidence: 0.9990757

01:00:03.705 --> 01:00:05.065
maximum in the first couple

NOTE Confidence: 0.9990757

01:00:05.065 --> 01:00:05.725
of cycles

NOTE Confidence: 0.999874

01:00:06.025 --> 01:00:06.525
of

NOTE Confidence: 0.87155604

01:00:08.105 --> 01:00:08.925
treatment with zolbituximab.

NOTE Confidence: 0.9490612

01:00:09.945 --> 01:00:10.445
And,

NOTE Confidence: 0.9865456

01:00:11.305 --> 01:00:12.985
for the medical oncologist listening

NOTE Confidence: 0.9865456

01:00:12.985 --> 01:00:14.345
to this talk, one would

NOTE Confidence: 0.9865456

01:00:14.345 --> 01:00:15.085
say, hey.

NOTE Confidence: 0.9892752

01:00:15.410 --> 01:00:16.290
We know how to deal

NOTE Confidence: 0.9892752

01:00:16.290 --> 01:00:18.530
with, high dose chemotherapy and

NOTE Confidence: 0.9892752

01:00:18.530 --> 01:00:19.650
nausea and vomiting, and this

NOTE Confidence: 0.9892752

01:00:19.650 --> 01:00:20.530
is not something that we

NOTE Confidence: 0.9892752

01:00:20.530 --> 01:00:21.650
need to be taught again.

NOTE Confidence: 0.9892752

01:00:21.650 --> 01:00:22.530
But the truth is that

NOTE Confidence: 0.9892752

01:00:22.530 --> 01:00:23.650
the nausea and vomiting for

NOTE Confidence: 0.9892752

01:00:23.650 --> 01:00:24.150
zolbituximab

NOTE Confidence: 0.9919917

01:00:24.610 --> 01:00:25.970
is so unique that they

NOTE Confidence: 0.9919917

01:00:25.970 --> 01:00:27.010
actually had to have a

NOTE Confidence: 0.9919917

01:00:27.010 --> 01:00:28.150
consensus guidelines

NOTE Confidence: 0.9613719

01:00:28.505 --> 01:00:29.705
for the management of the

NOTE Confidence: 0.9613719

01:00:29.705 --> 01:00:31.245
nausea and vomiting with zolpidemaximab.

NOTE Confidence: 0.9757508

01:00:31.785 --> 01:00:33.145
This was a consensus guideline

NOTE Confidence: 0.9757508

01:00:33.145 --> 01:00:34.185
just published a couple of

NOTE Confidence: 0.9757508

01:00:34.185 --> 01:00:35.885
months ago, and the recommendation

NOTE Confidence: 0.9550126

01:00:36.425 --> 01:00:38.025
is actually for using a

NOTE Confidence: 0.9550126

01:00:38.025 --> 01:00:40.105
highly hematogenic regimen with an

NOTE Confidence: 0.9550126

01:00:40.105 --> 01:00:41.165
NK1 inhibitor,

NOTE Confidence: 0.962303

01:00:41.705 --> 01:00:43.165
five HT3 inhibitor,

NOTE Confidence: 0.9071665

01:00:43.690 --> 01:00:44.190
dexamethasone,

NOTE Confidence: 0.99221325

01:00:44.490 --> 01:00:45.470
as well as olanzapine

NOTE Confidence: 0.8999043

01:00:46.010 --> 01:00:47.790
with other recommendations of triplet

NOTE Confidence: 0.8999043

01:00:48.010 --> 01:00:49.230
anti nausea, vomiting,

NOTE Confidence: 0.95696515

01:00:49.930 --> 01:00:51.450
regimens as well. But at

NOTE Confidence: 0.95696515

01:00:51.450 --> 01:00:52.890
Yale, we have actually adopted

NOTE Confidence: 0.95696515

01:00:52.890 --> 01:00:54.410
the four drug regimen for

NOTE Confidence: 0.95696515

01:00:54.410 --> 01:00:56.170
the treatment of patients receiving

NOTE Confidence: 0.95696515

01:00:56.170 --> 01:00:56.670
sorbituximab,

NOTE Confidence: 0.9532445

01:00:57.785 --> 01:00:58.985
And the nausea and vomiting

NOTE Confidence: 0.9532445

01:00:58.985 --> 01:01:00.185
has definitely been a lot

NOTE Confidence: 0.9532445

01:01:00.185 --> 01:01:00.925
more manageable

NOTE Confidence: 0.9948685

01:01:01.385 --> 01:01:02.525
with this regimen.

NOTE Confidence: 0.93013656

01:01:07.145 --> 01:01:08.185
Again, a couple of months

NOTE Confidence: 0.93013656

01:01:08.185 --> 01:01:09.305
ago, we also saw the

NOTE Confidence: 0.93013656

01:01:09.305 --> 01:01:10.825
results for joint analysis of

NOTE Confidence: 0.93013656

01:01:10.825 --> 01:01:12.270
both the Spotlight and Lou.

NOTE Confidence: 0.93013656

01:01:12.350 --> 01:01:14.030
Again reinforcing this idea that

NOTE Confidence: 0.93013656

01:01:14.030 --> 01:01:15.090
the addition of zolbituximab

NOTE Confidence: 0.9290588

01:01:15.790 --> 01:01:16.450
to chemotherapy

NOTE Confidence: 0.9987833

01:01:16.830 --> 01:01:17.490
was beneficial

NOTE Confidence: 0.9573283

01:01:17.790 --> 01:01:19.070
with a very nice hazards

NOTE Confidence: 0.9573283

01:01:19.070 --> 01:01:20.350
ratio of zero point seven

NOTE Confidence: 0.9573283

01:01:20.350 --> 01:01:21.730
seven for overall survival.

NOTE Confidence: 0.8680723

01:01:22.030 --> 01:01:22.990
And this was published in

NOTE Confidence: 0.8680723

01:01:22.990 --> 01:01:24.030
the New England of General

NOTE Confidence: 0.8680723

01:01:24.030 --> 01:01:24.530
Medicine,

NOTE Confidence: 0.9979938

01:01:25.070 --> 01:01:26.370
a couple of months ago.

NOTE Confidence: 0.97181416

01:01:28.155 --> 01:01:29.195
One of the things that

NOTE Confidence: 0.97181416

01:01:29.195 --> 01:01:30.735
are unique with gastric esophageal

NOTE Confidence: 0.97181416

01:01:30.795 --> 01:01:32.315
cancers is the fact that

NOTE Confidence: 0.97181416

01:01:32.315 --> 01:01:33.535
a lot of the biomarkers

NOTE Confidence: 0.97181416

01:01:33.595 --> 01:01:35.275
that we use are not

NOTE Confidence: 0.97181416

01:01:35.275 --> 01:01:37.435
oncogene drivers, and therefore are

NOTE Confidence: 0.97181416

01:01:37.435 --> 01:01:38.175
not uniquely

NOTE Confidence: 0.98056877

01:01:38.475 --> 01:01:40.290
present in each tumor. And

NOTE Confidence: 0.98056877

01:01:40.290 --> 01:01:41.170
there is a lot of

NOTE Confidence: 0.98056877

01:01:41.170 --> 01:01:42.470
overlap in the coexpression

NOTE Confidence: 0.9911601

01:01:42.770 --> 01:01:44.470
of these biomarkers in tumors.

NOTE Confidence: 0.9675822

01:01:44.770 --> 01:01:45.810
This means that there could

NOTE Confidence: 0.9675822

01:01:45.810 --> 01:01:47.170
be patients that have or

NOTE Confidence: 0.9675822

01:01:47.170 --> 01:01:48.610
tumors that have expression of

NOTE Confidence: 0.9675822

01:01:48.610 --> 01:01:50.150
both PD L1 and claudin,

NOTE Confidence: 0.9675822

01:01:50.370 --> 01:01:52.130
claudin and HER2. And there's

NOTE Confidence: 0.9675822

01:01:52.130 --> 01:01:53.410
a lot of because a

NOTE Confidence: 0.9675822

01:01:53.410 --> 01:01:55.175
lot of the targeted therapies

NOTE Confidence: 0.9675822

01:01:55.175 --> 01:01:56.775
are combined with chemotherapy in

NOTE Confidence: 0.9675822

01:01:56.775 --> 01:01:57.435
the frontline,

NOTE Confidence: 0.9971136

01:01:57.735 --> 01:01:58.875
there's a lot of confusion

NOTE Confidence: 0.9971136

01:01:59.015 --> 01:01:59.755
on whether,

NOTE Confidence: 0.9502647

01:02:00.215 --> 01:02:01.735
patients who have coexpression of

NOTE Confidence: 0.9502647

01:02:01.735 --> 01:02:03.175
both Claudin and PDL one,

NOTE Confidence: 0.9502647

01:02:03.175 --> 01:02:05.095
for example, should receive either

NOTE Confidence: 0.9502647

01:02:05.095 --> 01:02:05.595
immunotherapy

NOTE Confidence: 0.9897117

01:02:06.135 --> 01:02:08.215
or Claudin targeted therapies in

NOTE Confidence: 0.9897117

01:02:08.215 --> 01:02:08.715
frontline.

NOTE Confidence: 0.9216214

01:02:09.330 --> 01:02:10.690
And to actually answer this

NOTE Confidence: 0.9216214

01:02:10.690 --> 01:02:12.210
question, we are the the

NOTE Confidence: 0.9216214

01:02:12.210 --> 01:02:13.650
Lucerne trial is looking at

NOTE Confidence: 0.9216214

01:02:13.650 --> 01:02:15.750
both HER2 positive and PDL1

NOTE Confidence: 0.9216214

01:02:15.970 --> 01:02:17.830
positive metastatic gastrosophageal

NOTE Confidence: 0.87970865

01:02:18.210 --> 01:02:20.370
cancers and randomizing these patients

NOTE Confidence: 0.87970865

01:02:20.370 --> 01:02:22.230
who receive chemotherapy and pembrolizumab

NOTE Confidence: 0.95436937

01:02:22.930 --> 01:02:24.070
with or without zolbituximab.

NOTE Confidence: 0.9440243

01:02:24.865 --> 01:02:25.985
And this is another trial

NOTE Confidence: 0.9440243

01:02:25.985 --> 01:02:27.105
that's gonna be opening up

NOTE Confidence: 0.9440243

01:02:27.105 --> 01:02:28.305
at Yale soon for patients

NOTE Confidence: 0.9440243

01:02:28.305 --> 01:02:29.985
that have both expression of

NOTE Confidence: 0.9440243

01:02:29.985 --> 01:02:32.225
HER2 and, not HER2. Sorry.

NOTE Confidence: 0.9440243

01:02:32.225 --> 01:02:33.765
Of PDL one and claudin.

NOTE Confidence: 0.9487794

01:02:34.625 --> 01:02:35.845
This is an error. Sorry.

NOTE Confidence: 0.9794173

01:02:40.180 --> 01:02:41.079
And, of course,

NOTE Confidence: 0.9963938

01:02:41.380 --> 01:02:42.420
all of us are familiar

NOTE Confidence: 0.9963938

01:02:42.420 --> 01:02:43.799
with the idea of of,

NOTE Confidence: 0.98121333

01:02:44.740 --> 01:02:46.819
immunotherapy in combination with,

NOTE Confidence: 0.70559376

01:02:47.460 --> 01:02:47.960
chemotherapy

NOTE Confidence: 0.9631309

01:02:48.579 --> 01:02:50.500
for frontline treatment of metastatic,

NOTE Confidence: 0.9631309

01:02:50.500 --> 01:02:52.365
gastric, esophageal cancers. We have

NOTE Confidence: 0.9631309

01:02:52.365 --> 01:02:54.445
multiple different clinical trials with

NOTE Confidence: 0.9631309

01:02:54.445 --> 01:02:54.945
pembrolizumab,

NOTE Confidence: 0.99145377

01:02:55.485 --> 01:02:56.705
nivolumab, tislelizumab,

NOTE Confidence: 0.99319965

01:02:57.245 --> 01:02:58.845
all FDA approved for frontline

NOTE Confidence: 0.99319965

01:02:58.845 --> 01:02:59.345
treatment,

NOTE Confidence: 0.8768903

01:03:00.285 --> 01:03:01.665
in combination with chemotherapy.

NOTE Confidence: 0.9393696

01:03:02.765 --> 01:03:04.465
There's a lot of controversy

NOTE Confidence: 0.9393696

01:03:04.605 --> 01:03:06.400
around the PDL one cutoff.

NOTE Confidence: 0.9393696

01:03:06.400 --> 01:03:07.840
And as doctor Gibson mentioned,

NOTE Confidence: 0.9393696

01:03:07.840 --> 01:03:08.560
we are not going to

NOTE Confidence: 0.9393696

01:03:08.560 --> 01:03:09.760
go into that rabbit hole

NOTE Confidence: 0.9393696

01:03:09.760 --> 01:03:11.120
today. But the idea is

NOTE Confidence: 0.9393696

01:03:11.120 --> 01:03:11.620
that,

NOTE Confidence: 0.939337

01:03:12.000 --> 01:03:13.520
the general principle is that

NOTE Confidence: 0.939337

01:03:13.520 --> 01:03:15.620
for PD L1 experiencing tumors,

NOTE Confidence: 0.939337

01:03:15.760 --> 01:03:17.300
that the addition of immunotherapy

NOTE Confidence: 0.9588177

01:03:17.600 --> 01:03:19.140
to chemotherapy in frontline

NOTE Confidence: 0.9630162

01:03:19.520 --> 01:03:21.700
is, considered standard of care.

NOTE Confidence: 0.9908289

01:03:23.255 --> 01:03:24.535
One of the questions is,

NOTE Confidence: 0.9908289

01:03:24.535 --> 01:03:25.415
is there a role for

NOTE Confidence: 0.9908289

01:03:25.415 --> 01:03:27.435
the continuation of immunotherapy

NOTE Confidence: 0.9682118

01:03:27.735 --> 01:03:29.415
into second line? And here

NOTE Confidence: 0.9682118

01:03:29.415 --> 01:03:30.955
we have the PARAMUNE study,

NOTE Confidence: 0.9682118

01:03:31.095 --> 01:03:32.695
which is looking at adding

NOTE Confidence: 0.9682118

01:03:32.695 --> 01:03:33.195
nivolumab

NOTE Confidence: 0.9812114

01:03:33.495 --> 01:03:35.015
to a second line regimen

NOTE Confidence: 0.9812114

01:03:35.015 --> 01:03:36.555
of paclitaxel and ramasirumab

NOTE Confidence: 0.9108539

01:03:37.220 --> 01:03:38.579
for tumors that have a

NOTE Confidence: 0.9108539

01:03:38.579 --> 01:03:40.260
PD L1 CPS score of

NOTE Confidence: 0.9108539

01:03:40.260 --> 01:03:41.079
one or greater.

NOTE Confidence: 0.93183285

01:03:41.940 --> 01:03:43.220
And this study is also

NOTE Confidence: 0.93183285

01:03:43.220 --> 01:03:44.119
gonna be opening,

NOTE Confidence: 0.99858934

01:03:45.140 --> 01:03:46.279
at Yale soon.

NOTE Confidence: 0.93859994

01:03:49.345 --> 01:03:50.785
And lastly, moving into the

NOTE Confidence: 0.93859994

01:03:50.785 --> 01:03:52.645
earlier phase of resectable gastroesophageal

NOTE Confidence: 0.97197264

01:03:53.025 --> 01:03:53.845
cancer space,

NOTE Confidence: 0.98855704

01:03:54.625 --> 01:03:56.005
we have had the CheckMate

NOTE Confidence: 0.98855704

01:03:56.065 --> 01:03:57.745
five seventy seven study that

NOTE Confidence: 0.98855704

01:03:57.745 --> 01:03:59.025
looked at patients that had

NOTE Confidence: 0.98855704

01:03:59.025 --> 01:04:00.085
undergone chemoradiation

NOTE Confidence: 0.9026021

01:04:00.385 --> 01:04:01.839
and surgery, and then,

NOTE Confidence: 0.95400494

01:04:02.240 --> 01:04:03.680
did not for those who

NOTE Confidence: 0.95400494

01:04:03.680 --> 01:04:05.140
had not achieved a pathological

NOTE Confidence: 0.95400494

01:04:05.280 --> 01:04:07.280
complete response were randomized to

NOTE Confidence: 0.95400494

01:04:07.280 --> 01:04:09.220
either receive nivolumab or placebo.

NOTE Confidence: 0.9670264

01:04:09.520 --> 01:04:10.720
And this study had a

NOTE Confidence: 0.9670264

01:04:10.720 --> 01:04:12.480
disease free survival benefit, and

NOTE Confidence: 0.9670264

01:04:12.480 --> 01:04:13.440
this has been something that

NOTE Confidence: 0.9670264

01:04:13.440 --> 01:04:14.480
we have been offering our

NOTE Confidence: 0.9670264

01:04:14.480 --> 01:04:14.980
patients.

NOTE Confidence: 0.80230856

01:04:15.359 --> 01:04:15.859
But,

NOTE Confidence: 0.9723106

01:04:17.735 --> 01:04:18.535
in a couple of months,

NOTE Confidence: 0.9723106

01:04:18.535 --> 01:04:19.255
we are going to see

NOTE Confidence: 0.9723106

01:04:19.255 --> 01:04:20.855
the overall survival data that

NOTE Confidence: 0.9723106

01:04:20.855 --> 01:04:21.815
are going to be presented

NOTE Confidence: 0.9723106

01:04:21.815 --> 01:04:22.635
at ASCO.

NOTE Confidence: 0.96729916

01:04:23.015 --> 01:04:23.975
And we are looking forward

NOTE Confidence: 0.96729916

01:04:23.975 --> 01:04:25.095
to see whether the overall

NOTE Confidence: 0.96729916

01:04:25.095 --> 01:04:26.455
survival will be positive for

NOTE Confidence: 0.96729916

01:04:26.455 --> 01:04:27.675
this important trial.

NOTE Confidence: 0.9552657

01:04:28.775 --> 01:04:30.055
We also saw data from

NOTE Confidence: 0.9552657

01:04:30.055 --> 01:04:31.950
KEYNOTE-five eighty five that looked

NOTE Confidence: 0.9552657

01:04:31.950 --> 01:04:33.330
at the addition of pembrolizumab

NOTE Confidence: 0.86257094

01:04:33.950 --> 01:04:35.650
two chemotherapy in the perioperative

NOTE Confidence: 0.94180804

01:04:36.030 --> 01:04:38.030
setting followed by surgery. And

NOTE Confidence: 0.94180804

01:04:38.030 --> 01:04:39.390
this was actually a negative

NOTE Confidence: 0.94180804

01:04:39.390 --> 01:04:40.609
trial where,

NOTE Confidence: 0.9555266

01:04:41.230 --> 01:04:42.770
although there was an event

NOTE Confidence: 0.9555266

01:04:42.830 --> 01:04:44.830
event free survival benefit, this

NOTE Confidence: 0.9555266

01:04:44.830 --> 01:04:46.849
did not achieve statistical significance

NOTE Confidence: 0.99812746

01:04:47.335 --> 01:04:49.015
and the overall survival benefit

NOTE Confidence: 0.99812746

01:04:49.015 --> 01:04:49.675
was not

NOTE Confidence: 0.9454245

01:04:50.055 --> 01:04:50.555
positive

NOTE Confidence: 0.99276924

01:04:50.855 --> 01:04:52.715
for the addition of pembrolizumab

NOTE Confidence: 0.668659

01:04:53.175 --> 01:04:53.915
two chemotherapy.

NOTE Confidence: 0.93426174

01:04:55.255 --> 01:04:56.935
However, we also saw data

NOTE Confidence: 0.93426174

01:04:56.935 --> 01:04:58.295
from the MATAHONE study that

NOTE Confidence: 0.93426174

01:04:58.295 --> 01:05:00.235
was a more cleanly designed,

NOTE Confidence: 0.95090187

01:05:00.690 --> 01:05:03.010
single endpoint study and with

NOTE Confidence: 0.95090187

01:05:03.010 --> 01:05:04.470
a more consistent chemotherapy

NOTE Confidence: 0.92861253

01:05:04.770 --> 01:05:06.150
backbone with FLOT,

NOTE Confidence: 0.94173247

01:05:06.450 --> 01:05:07.970
and in this study, patients

NOTE Confidence: 0.94173247

01:05:07.970 --> 01:05:10.450
with FLOT were, come were

NOTE Confidence: 0.94173247

01:05:10.450 --> 01:05:12.230
randomized to either receive durvalumab

NOTE Confidence: 0.9239268

01:05:12.690 --> 01:05:14.575
or placebo and then underwent

NOTE Confidence: 0.9239268

01:05:14.575 --> 01:05:16.595
surgery and then either continue

NOTE Confidence: 0.9239268

01:05:16.815 --> 01:05:18.655
with durvalumab and FLOT. And

NOTE Confidence: 0.9239268

01:05:18.655 --> 01:05:20.255
this study, we saw earlier

NOTE Confidence: 0.9239268

01:05:20.255 --> 01:05:20.755
data,

NOTE Confidence: 0.9961098

01:05:21.135 --> 01:05:22.335
looking at an improvement in

NOTE Confidence: 0.9961098

01:05:22.335 --> 01:05:22.835
pathological

NOTE Confidence: 0.96320426

01:05:23.135 --> 01:05:25.375
complete response of nineteen percent

NOTE Confidence: 0.96320426

01:05:25.375 --> 01:05:27.640
versus seven percent. But, at

NOTE Confidence: 0.96320426

01:05:27.640 --> 01:05:29.080
ASCO this year, we are

NOTE Confidence: 0.96320426

01:05:29.080 --> 01:05:30.920
gonna see, as a plenary

NOTE Confidence: 0.96320426

01:05:30.920 --> 01:05:32.780
session, the event free survival,

NOTE Confidence: 0.9186796

01:05:33.240 --> 01:05:33.980
of Matterhorn,

NOTE Confidence: 0.94569683

01:05:34.280 --> 01:05:35.960
and the press release announced

NOTE Confidence: 0.94569683

01:05:35.960 --> 01:05:37.080
that this had achieved its

NOTE Confidence: 0.94569683

01:05:37.080 --> 01:05:38.119
primary endpoint and is a

NOTE Confidence: 0.94569683

01:05:38.119 --> 01:05:39.400
positive study. So this is

NOTE Confidence: 0.94569683

01:05:39.400 --> 01:05:41.180
definitely gonna be practice changing,

NOTE Confidence: 0.94569683

01:05:41.375 --> 01:05:43.135
and very likely patients are

NOTE Confidence: 0.94569683

01:05:43.135 --> 01:05:44.174
going to start going to

NOTE Confidence: 0.94569683

01:05:44.174 --> 01:05:44.915
be offered,

NOTE Confidence: 0.9095459

01:05:45.535 --> 01:05:47.234
FLOT in combination with dorvelumab,

NOTE Confidence: 0.874245

01:05:48.174 --> 01:05:49.635
or resectable gastroesophageal

NOTE Confidence: 0.9983559

01:05:50.174 --> 01:05:50.674
adenocarcinomas.

NOTE Confidence: 0.98272085

01:05:52.655 --> 01:05:53.535
And we are going to

NOTE Confidence: 0.98272085

01:05:53.535 --> 01:05:55.020
have multiple on the background

NOTE Confidence: 0.98272085

01:05:55.020 --> 01:05:55.820
of that, we are going

NOTE Confidence: 0.98272085

01:05:55.820 --> 01:05:57.760
to have multiple perioperative chemotherapy

NOTE Confidence: 0.9669682

01:05:58.460 --> 01:06:00.780
plus, novel therapeutic trials that

NOTE Confidence: 0.9669682

01:06:00.780 --> 01:06:01.980
are opening up at Yale

NOTE Confidence: 0.9669682

01:06:01.980 --> 01:06:02.700
in the next,

NOTE Confidence: 0.999078

01:06:03.100 --> 01:06:03.840
few months.

NOTE Confidence: 0.99773484

01:06:05.100 --> 01:06:05.820
At the end of the

NOTE Confidence: 0.99773484

01:06:05.820 --> 01:06:07.660
day, from a systemic therapy

NOTE Confidence: 0.99773484

01:06:07.660 --> 01:06:08.160
perspective,

NOTE Confidence: 0.9252017

01:06:08.525 --> 01:06:09.645
I think Doctor. Gibson will

NOTE Confidence: 0.9252017

01:06:09.645 --> 01:06:11.085
also agree that we should

NOTE Confidence: 0.9252017

01:06:11.085 --> 01:06:12.925
be testing all our biomarkers

NOTE Confidence: 0.9252017

01:06:12.925 --> 01:06:15.165
upfront for HER2 PDL1 claudine

NOTE Confidence: 0.9252017

01:06:15.165 --> 01:06:16.525
as well as mismatch repair

NOTE Confidence: 0.9252017

01:06:16.525 --> 01:06:17.025
deficiency.

NOTE Confidence: 0.9333852

01:06:17.645 --> 01:06:18.685
We know that addition of

NOTE Confidence: 0.9333852

01:06:18.685 --> 01:06:19.185
pembrolizumab

NOTE Confidence: 0.8252821

01:06:19.485 --> 01:06:21.345
two chemotherapy and HER2 positive,

NOTE Confidence: 0.9959966

01:06:22.150 --> 01:06:22.650
tumors

NOTE Confidence: 0.9342676

01:06:22.950 --> 01:06:24.630
are beneficial except in PD

NOTE Confidence: 0.9342676

01:06:24.630 --> 01:06:25.850
L1 negative tumors.

NOTE Confidence: 0.9850421

01:06:26.390 --> 01:06:27.450
The addition of zolbituximab

NOTE Confidence: 0.9555306

01:06:28.150 --> 01:06:28.810
is important,

NOTE Confidence: 0.9463174

01:06:29.350 --> 01:06:30.630
for patients that are claudan

NOTE Confidence: 0.9463174

01:06:30.630 --> 01:06:31.770
eighteen point two positive,

NOTE Confidence: 0.9785141

01:06:32.070 --> 01:06:33.930
but, the management of toxicities

NOTE Confidence: 0.8906624

01:06:34.230 --> 01:06:34.970
will be key.

NOTE Confidence: 0.9271035

01:06:36.695 --> 01:06:38.535
Darvelumab in combination with FLOT

NOTE Confidence: 0.9271035

01:06:38.535 --> 01:06:39.895
is likely to be practice

NOTE Confidence: 0.9271035

01:06:39.895 --> 01:06:40.935
changing in the next few

NOTE Confidence: 0.9271035

01:06:40.935 --> 01:06:42.855
months. And we have multiple

NOTE Confidence: 0.9271035

01:06:42.855 --> 01:06:44.135
trial options for patients with

NOTE Confidence: 0.9271035

01:06:44.135 --> 01:06:46.295
gastrointestinal cancers across the entire

NOTE Confidence: 0.9271035

01:06:46.295 --> 01:06:46.795
network.

NOTE Confidence: 0.96702904

01:06:47.735 --> 01:06:49.255
And, with that, I'm going

NOTE Confidence: 0.96702904

01:06:49.255 --> 01:06:50.955
to, end my talk.

NOTE Confidence: 0.93380165

01:06:58.150 --> 01:06:59.550
We do have a a

NOTE Confidence: 0.93380165

01:06:59.550 --> 01:07:00.470
a few more minutes for

NOTE Confidence: 0.93380165

01:07:00.470 --> 01:07:01.990
question and answers. I encourage

NOTE Confidence: 0.93380165

01:07:01.990 --> 01:07:04.090
folks to, drop in questions

NOTE Confidence: 0.93380165

01:07:04.150 --> 01:07:04.970
into the,

NOTE Confidence: 0.9640831

01:07:05.270 --> 01:07:06.310
either into the chat or

NOTE Confidence: 0.9640831

01:07:06.310 --> 01:07:07.270
into the q and a

NOTE Confidence: 0.9640831

01:07:07.270 --> 01:07:07.665
box.

NOTE Confidence: 0.99622613

01:07:08.625 --> 01:07:09.365
In the meanwhile,

NOTE Confidence: 0.97272545

01:07:09.905 --> 01:07:11.205
we we have,

NOTE Confidence: 0.9911337

01:07:12.225 --> 01:07:12.945
one of our,

NOTE Confidence: 0.9050329

01:07:13.265 --> 01:07:14.245
attendees who's,

NOTE Confidence: 0.96473247

01:07:14.705 --> 01:07:16.465
actually an esophageal cancer survivor

NOTE Confidence: 0.96473247

01:07:16.465 --> 01:07:18.225
who's gone through the entire

NOTE Confidence: 0.96473247

01:07:18.225 --> 01:07:19.285
journey of chemoradiation

NOTE Confidence: 0.934466

01:07:19.665 --> 01:07:20.645
as well as surgery,

NOTE Confidence: 0.98366195

01:07:20.945 --> 01:07:22.485
and perhaps we could give

NOTE Confidence: 0.99113035

01:07:23.520 --> 01:07:24.020
miss

NOTE Confidence: 0.9884436

01:07:24.480 --> 01:07:24.980
Deepika

NOTE Confidence: 0.9776625

01:07:25.360 --> 01:07:27.440
a chance to talk. Emily,

NOTE Confidence: 0.9776625

01:07:27.440 --> 01:07:28.500
do you think we could

NOTE Confidence: 0.9776625

01:07:28.640 --> 01:07:29.440
see if we could get

NOTE Confidence: 0.9776625

01:07:29.440 --> 01:07:29.940
Deepika,

NOTE Confidence: 0.95819646

01:07:31.040 --> 01:07:32.240
speaking right, or is she

NOTE Confidence: 0.95819646

01:07:32.240 --> 01:07:33.780
already a panelist with us?

NOTE Confidence: 0.9094937

01:07:37.805 --> 01:07:39.645
Okay. I think Deepika has

NOTE Confidence: 0.9094937

01:07:39.645 --> 01:07:40.145
speaking.

NOTE Confidence: 0.9992243

01:07:41.565 --> 01:07:42.625
Deepika, can you hear us?

NOTE Confidence: 0.9734708

01:07:43.005 --> 01:07:44.125
Yeah. I can hear you,

NOTE Confidence: 0.9734708

01:07:44.125 --> 01:07:45.744
but am I audible?

NOTE Confidence: 0.97470987

01:07:47.484 --> 01:07:49.089
Hi. Thanks for thanks for

NOTE Confidence: 0.97470987

01:07:49.089 --> 01:07:50.869
joining the call and, for,

NOTE Confidence: 0.83664477

01:07:51.890 --> 01:07:53.490
dialing in dialing in. Like

NOTE Confidence: 0.83664477

01:07:53.490 --> 01:07:54.530
to share Let's share with

NOTE Confidence: 0.83664477

01:07:54.530 --> 01:07:55.030
us

NOTE Confidence: 0.8141272

01:07:55.390 --> 01:07:55.890
a

NOTE Confidence: 0.97761756

01:07:56.250 --> 01:07:56.750
little

NOTE Confidence: 0.664279

01:07:57.109 --> 01:07:57.609
bit.

NOTE Confidence: 0.9529146

01:07:57.970 --> 01:07:59.510
Yeah. Am am I audible?

NOTE Confidence: 0.97222936

01:08:01.315 --> 01:08:02.355
Yeah. It's a little bit

NOTE Confidence: 0.97222936

01:08:02.355 --> 01:08:04.295
faint, but, maybe you could

NOTE Confidence: 0.7283297

01:08:04.835 --> 01:08:06.375
Hey. Into the mic, please.

NOTE Confidence: 0.9465224

01:08:07.395 --> 01:08:08.755
Yeah. I am sorry for

NOTE Confidence: 0.9465224

01:08:08.755 --> 01:08:08.995
that,

NOTE Confidence: 0.93165743

01:08:10.355 --> 01:08:12.195
for the voice thing because

NOTE Confidence: 0.95157516

01:08:13.155 --> 01:08:14.595
one more. Hello. Am I

NOTE Confidence: 0.95157516

01:08:14.595 --> 01:08:15.895
am I audible now?

NOTE Confidence: 0.94797224

01:08:16.880 --> 01:08:17.920
Yeah. Please go ahead. It'll

NOTE Confidence: 0.94797224

01:08:17.920 --> 01:08:18.880
be it'll be great to

NOTE Confidence: 0.94797224

01:08:18.880 --> 01:08:20.340
hear your, journey,

NOTE Confidence: 0.99958545

01:08:20.719 --> 01:08:21.780
through this entire

NOTE Confidence: 0.5881271

01:08:24.479 --> 01:08:25.300
Okay. Process.

NOTE Confidence: 0.88987

01:08:26.079 --> 01:08:27.599
I I I'm sorry. I'm

NOTE Confidence: 0.88987

01:08:27.599 --> 01:08:29.619
sorry about my voice. So

NOTE Confidence: 0.9637112

01:08:30.195 --> 01:08:32.195
hello, everyone. I'm Deepika Karki.

NOTE Confidence: 0.9637112

01:08:32.195 --> 01:08:32.935
I'm currently

NOTE Confidence: 0.9777539

01:08:33.554 --> 01:08:35.314
a research fellow at Mayo

NOTE Confidence: 0.9777539

01:08:35.314 --> 01:08:35.814
Clinic,

NOTE Confidence: 0.9788977

01:08:36.275 --> 01:08:37.574
Jacksonville, Florida.

NOTE Confidence: 0.9970282

01:08:38.354 --> 01:08:39.474
And as of today, I

NOTE Confidence: 0.9970282

01:08:39.474 --> 01:08:41.255
am four years cancer free.

NOTE Confidence: 0.9921929

01:08:41.635 --> 01:08:43.494
I was diagnosed with esophageal

NOTE Confidence: 0.9921929

01:08:43.715 --> 01:08:44.215
cancer

NOTE Confidence: 0.9511399

01:08:44.755 --> 01:08:45.689
when I was,

NOTE Confidence: 0.99655896

01:08:46.410 --> 01:08:47.710
twenty five years old,

NOTE Confidence: 0.9586689

01:08:48.090 --> 01:08:49.390
which is four years ago,

NOTE Confidence: 0.9985895

01:08:50.090 --> 01:08:51.370
and I was diagnosed on

NOTE Confidence: 0.9985895

01:08:51.370 --> 01:08:52.989
the in the initial stages.

NOTE Confidence: 0.99038595

01:08:54.650 --> 01:08:56.750
It was a squamous cancer,

NOTE Confidence: 0.99038595

01:08:56.810 --> 01:08:58.489
and it was it was

NOTE Confidence: 0.99038595

01:08:58.489 --> 01:09:00.410
located thirty eight centimeters from

NOTE Confidence: 0.99038595

01:09:00.410 --> 01:09:01.070
the incisors.

NOTE Confidence: 0.9853849

01:09:02.075 --> 01:09:04.075
It was fifteen centimeters long,

NOTE Confidence: 0.9853849

01:09:04.075 --> 01:09:06.015
and it was two millimeters

NOTE Confidence: 0.9853849

01:09:06.314 --> 01:09:06.814
thickness.

NOTE Confidence: 0.99793166

01:09:07.435 --> 01:09:08.955
So I had multiple rounds

NOTE Confidence: 0.99793166

01:09:08.955 --> 01:09:09.695
of chemotherapy,

NOTE Confidence: 0.9992971

01:09:10.875 --> 01:09:11.375
radiotherapy

NOTE Confidence: 0.91093135

01:09:11.835 --> 01:09:13.435
followed by resection of my

NOTE Confidence: 0.91093135

01:09:13.435 --> 01:09:13.935
esophagus.

NOTE Confidence: 0.99849

01:09:14.875 --> 01:09:15.375
And

NOTE Confidence: 0.9906889

01:09:15.900 --> 01:09:16.640
post resection,

NOTE Confidence: 0.9966159

01:09:17.740 --> 01:09:19.260
one of the complications that

NOTE Confidence: 0.9966159

01:09:19.260 --> 01:09:20.479
I'm facing is

NOTE Confidence: 0.9798711

01:09:20.860 --> 01:09:22.460
the paralysis of my right

NOTE Confidence: 0.9798711

01:09:22.460 --> 01:09:24.620
vocal cord. Hence, my voice

NOTE Confidence: 0.9798711

01:09:24.620 --> 01:09:26.540
is very hoarse, and I'm

NOTE Confidence: 0.9798711

01:09:26.540 --> 01:09:27.600
sorry for that.

NOTE Confidence: 0.98363125

01:09:28.155 --> 01:09:29.195
But, yeah, it was a

NOTE Confidence: 0.98363125

01:09:29.195 --> 01:09:30.954
great talk, and, you know,

NOTE Confidence: 0.98363125

01:09:30.954 --> 01:09:32.155
it's really nice to see

NOTE Confidence: 0.98363125

01:09:32.155 --> 01:09:32.895
all the

NOTE Confidence: 0.9990439

01:09:33.354 --> 01:09:35.195
developments that has been happening

NOTE Confidence: 0.9990439

01:09:35.195 --> 01:09:36.094
in this field.

NOTE Confidence: 0.9380082

01:09:36.715 --> 01:09:38.415
I'm from Nepal originally,

NOTE Confidence: 0.98141134

01:09:39.195 --> 01:09:40.795
so all my treatment was

NOTE Confidence: 0.98141134

01:09:40.795 --> 01:09:42.554
done there, and it does

NOTE Confidence: 0.98141134

01:09:42.554 --> 01:09:44.850
not have as many resources

NOTE Confidence: 0.85564226

01:09:45.150 --> 01:09:46.990
as that was stocked in

NOTE Confidence: 0.85564226

01:09:46.990 --> 01:09:47.490
this

NOTE Confidence: 0.98696315

01:09:47.870 --> 01:09:50.450
amazing webinar today. But, yeah,

NOTE Confidence: 0.98696315

01:09:50.510 --> 01:09:52.350
just wanted to share it

NOTE Confidence: 0.98696315

01:09:52.350 --> 01:09:53.410
with all of you.

NOTE Confidence: 0.91218054

01:09:56.265 --> 01:09:58.025
Thanks, Deepika. It's it's really

NOTE Confidence: 0.91218054

01:09:58.025 --> 01:09:59.625
great to have, a success

NOTE Confidence: 0.91218054

01:09:59.625 --> 01:10:00.745
story and it's very difficult

NOTE Confidence: 0.91218054

01:10:00.745 --> 01:10:02.905
to, treat tumor type, and,

NOTE Confidence: 0.99041593

01:10:03.225 --> 01:10:04.844
it's great to see you,

NOTE Confidence: 0.95091975

01:10:06.344 --> 01:10:07.545
talk so proudly about your

NOTE Confidence: 0.95091975

01:10:07.545 --> 01:10:08.905
illness and share so greatly

NOTE Confidence: 0.95091975

01:10:08.905 --> 01:10:09.945
about the journey that you've

NOTE Confidence: 0.95091975

01:10:09.945 --> 01:10:10.685
gone through.

NOTE Confidence: 0.9967039

01:10:11.280 --> 01:10:12.560
Yeah. So a few points,

NOTE Confidence: 0.9967039

01:10:12.880 --> 01:10:14.080
that I wanted to talk

NOTE Confidence: 0.9967039

01:10:14.080 --> 01:10:15.540
about after listening to

NOTE Confidence: 0.95514804

01:10:15.920 --> 01:10:17.280
all the wonderful speakers was

NOTE Confidence: 0.95514804

01:10:17.280 --> 01:10:18.880
that, we didn't talk a

NOTE Confidence: 0.95514804

01:10:18.880 --> 01:10:20.660
lot about radiation pneumonitis,

NOTE Confidence: 0.9965068

01:10:21.439 --> 01:10:22.800
and that's something that I

NOTE Confidence: 0.9965068

01:10:22.800 --> 01:10:23.540
live with.

NOTE Confidence: 0.9711579

01:10:23.920 --> 01:10:25.635
And, you know, and, also,

NOTE Confidence: 0.9711579

01:10:25.635 --> 01:10:26.994
currently, I'm working on this

NOTE Confidence: 0.9711579

01:10:26.994 --> 01:10:28.114
project that is kind of

NOTE Confidence: 0.9711579

01:10:28.114 --> 01:10:29.175
looking at the

NOTE Confidence: 0.98425007

01:10:29.554 --> 01:10:31.255
cognitive function in patients,

NOTE Confidence: 0.95605105

01:10:32.275 --> 01:10:33.155
who are die who are

NOTE Confidence: 0.95605105

01:10:33.155 --> 01:10:34.835
diagnosed with cancer, you know,

NOTE Confidence: 0.95605105

01:10:34.835 --> 01:10:36.994
in their adolescent period at

NOTE Confidence: 0.95605105

01:10:36.994 --> 01:10:38.215
a very young age.

NOTE Confidence: 0.998623

01:10:38.830 --> 01:10:40.110
So I actually did a

NOTE Confidence: 0.998623

01:10:40.110 --> 01:10:41.410
case report on myself

NOTE Confidence: 0.972751

01:10:42.030 --> 01:10:42.910
that I'm more than happy

NOTE Confidence: 0.972751

01:10:42.910 --> 01:10:43.949
to share with the team.

NOTE Confidence: 0.972751

01:10:43.949 --> 01:10:45.229
And I feel like if

NOTE Confidence: 0.972751

01:10:45.229 --> 01:10:46.770
we could have more trials

NOTE Confidence: 0.99145985

01:10:47.469 --> 01:10:49.090
targeting on, like, young,

NOTE Confidence: 0.99497867

01:10:49.469 --> 01:10:51.489
you know, young patient cohort

NOTE Confidence: 0.99497867

01:10:51.550 --> 01:10:52.050
group

NOTE Confidence: 0.89927614

01:10:52.429 --> 01:10:54.050
because we mainly talk about

NOTE Confidence: 0.97441417

01:10:54.485 --> 01:10:56.165
therapies for elderly or, you

NOTE Confidence: 0.97441417

01:10:56.165 --> 01:10:57.945
know, young pediatric patients.

NOTE Confidence: 0.99847865

01:10:58.405 --> 01:10:59.205
But we don't have a

NOTE Confidence: 0.99847865

01:10:59.205 --> 01:11:01.045
lot of trials that kind

NOTE Confidence: 0.99847865

01:11:01.045 --> 01:11:02.405
of look at a major

NOTE Confidence: 0.99847865

01:11:02.405 --> 01:11:04.085
chunk, you know, of that

NOTE Confidence: 0.99847865

01:11:04.085 --> 01:11:04.585
particular

NOTE Confidence: 0.9863863

01:11:04.885 --> 01:11:06.990
patient population, and we talked

NOTE Confidence: 0.9863863

01:11:06.990 --> 01:11:08.850
about quality of life too.

NOTE Confidence: 0.9863863

01:11:08.990 --> 01:11:10.270
So my voice is something

NOTE Confidence: 0.9863863

01:11:10.270 --> 01:11:11.150
that I kind of have

NOTE Confidence: 0.9863863

01:11:11.150 --> 01:11:12.850
to explain on an everyday

NOTE Confidence: 0.9863863

01:11:12.910 --> 01:11:13.410
basis.

NOTE Confidence: 0.9610504

01:11:14.350 --> 01:11:15.550
So that's that. And I

NOTE Confidence: 0.9610504

01:11:15.550 --> 01:11:16.370
was initially

NOTE Confidence: 0.9782476

01:11:16.990 --> 01:11:18.450
I had dumping syndrome,

NOTE Confidence: 0.9478572

01:11:18.865 --> 01:11:20.785
which was very bad. And

NOTE Confidence: 0.9478572

01:11:20.785 --> 01:11:22.945
even now, I sometimes have

NOTE Confidence: 0.9478572

01:11:22.945 --> 01:11:24.005
posterior hypertension

NOTE Confidence: 0.98811483

01:11:24.865 --> 01:11:25.685
and hypoglycemia.

NOTE Confidence: 0.9957947

01:11:26.785 --> 01:11:27.825
So those are some of

NOTE Confidence: 0.9957947

01:11:27.825 --> 01:11:29.445
the quality of life barriers

NOTE Confidence: 0.9957947

01:11:29.505 --> 01:11:30.165
for me.

NOTE Confidence: 0.9639097

01:11:30.800 --> 01:11:32.640
And, yeah, just something that

NOTE Confidence: 0.9639097

01:11:32.640 --> 01:11:33.940
I wanted to share about

NOTE Confidence: 0.9639097

01:11:34.080 --> 01:11:35.040
with the team, with the

NOTE Confidence: 0.9639097

01:11:35.040 --> 01:11:36.740
prospects of maybe

NOTE Confidence: 0.9950657

01:11:37.600 --> 01:11:39.700
maybe, like, more amazing projects

NOTE Confidence: 0.9950657

01:11:39.760 --> 01:11:41.360
that might just come up

NOTE Confidence: 0.9950657

01:11:41.360 --> 01:11:42.180
in the future.

NOTE Confidence: 0.9545496

01:11:44.885 --> 01:11:45.925
Thanks, Deepika. I think you

NOTE Confidence: 0.9545496

01:11:45.925 --> 01:11:46.965
bring up some very, very

NOTE Confidence: 0.9545496

01:11:46.965 --> 01:11:47.845
good points, and maybe we

NOTE Confidence: 0.9545496

01:11:47.845 --> 01:11:48.885
could use this as the

NOTE Confidence: 0.9545496

01:11:48.885 --> 01:11:49.925
starting point for some of

NOTE Confidence: 0.9545496

01:11:49.925 --> 01:11:51.285
the discussions that we wanted

NOTE Confidence: 0.9545496

01:11:51.285 --> 01:11:52.405
to have. And I think

NOTE Confidence: 0.9545496

01:11:52.405 --> 01:11:53.765
both doctor Balfa and doctor

NOTE Confidence: 0.9545496

01:11:53.765 --> 01:11:54.585
Nus spoke,

NOTE Confidence: 0.97837484

01:11:55.125 --> 01:11:56.585
about this point that

NOTE Confidence: 0.9992955

01:11:56.920 --> 01:11:58.519
we need to correctly select

NOTE Confidence: 0.9992955

01:11:58.519 --> 01:11:59.900
the folks that may

NOTE Confidence: 0.97686124

01:12:00.280 --> 01:12:02.119
benefit from radiation and also

NOTE Confidence: 0.97686124

01:12:02.119 --> 01:12:03.559
be spared from radiation and

NOTE Confidence: 0.97686124

01:12:03.559 --> 01:12:05.179
similarly benefit from,

NOTE Confidence: 0.97424245

01:12:05.800 --> 01:12:07.159
surgery and be spared from

NOTE Confidence: 0.97424245

01:12:07.159 --> 01:12:08.599
surgery. And this brings up

NOTE Confidence: 0.97424245

01:12:08.599 --> 01:12:09.659
this point that,

NOTE Confidence: 0.90806925

01:12:10.215 --> 01:12:11.255
all all the patients that

NOTE Confidence: 0.90806925

01:12:11.255 --> 01:12:12.375
are treated at Yale are

NOTE Confidence: 0.90806925

01:12:12.375 --> 01:12:13.435
discussing a multidisciplinary

NOTE Confidence: 0.85814667

01:12:13.814 --> 01:12:15.354
tumor board. Very often,

NOTE Confidence: 0.9626075

01:12:15.814 --> 01:12:16.614
the four of us are

NOTE Confidence: 0.9626075

01:12:16.614 --> 01:12:18.135
on those tumor boards discussing

NOTE Confidence: 0.9626075

01:12:18.135 --> 01:12:19.094
who would be the right

NOTE Confidence: 0.9626075

01:12:19.094 --> 01:12:20.295
patients to get the right

NOTE Confidence: 0.9626075

01:12:20.295 --> 01:12:21.114
sort of treatments.

NOTE Confidence: 0.99251395

01:12:21.574 --> 01:12:22.074
And,

NOTE Confidence: 0.99362403

01:12:22.455 --> 01:12:23.655
we are reaching a point

NOTE Confidence: 0.99362403

01:12:23.655 --> 01:12:24.215
where we are,

NOTE Confidence: 0.9618455

01:12:25.620 --> 01:12:27.639
getting to a more personalized

NOTE Confidence: 0.9618455

01:12:27.699 --> 01:12:28.600
sort of treatment

NOTE Confidence: 0.96224326

01:12:28.979 --> 01:12:30.659
using biomarkers and other sort

NOTE Confidence: 0.96224326

01:12:30.659 --> 01:12:32.260
of strategies to decide on

NOTE Confidence: 0.96224326

01:12:32.260 --> 01:12:33.800
which patients should be benefiting

NOTE Confidence: 0.9711886

01:12:34.179 --> 01:12:36.020
from which aspects of the

NOTE Confidence: 0.9711886

01:12:36.020 --> 01:12:37.300
various therapies that we have

NOTE Confidence: 0.9711886

01:12:37.300 --> 01:12:37.800
available.

NOTE Confidence: 0.95985633

01:12:38.595 --> 01:12:39.315
But maybe it would be

NOTE Confidence: 0.95985633

01:12:39.315 --> 01:12:40.755
nice to hear from, doctor

NOTE Confidence: 0.95985633

01:12:40.755 --> 01:12:41.715
Du and doctor Boffa a

NOTE Confidence: 0.95985633

01:12:41.715 --> 01:12:43.075
little bit on the the

NOTE Confidence: 0.95985633

01:12:43.075 --> 01:12:44.195
thoughts that we go through

NOTE Confidence: 0.95985633

01:12:44.195 --> 01:12:46.115
when we decide on these,

NOTE Confidence: 0.9936233

01:12:46.835 --> 01:12:48.355
cases on whether we should

NOTE Confidence: 0.9936233

01:12:48.355 --> 01:12:49.955
be offering radiation as well

NOTE Confidence: 0.9936233

01:12:49.955 --> 01:12:51.095
as offering surgery.

NOTE Confidence: 0.99611425

01:12:54.420 --> 01:12:54.920
Sure.

NOTE Confidence: 0.9910341

01:12:55.380 --> 01:12:57.139
You know, Deepika, thank you

NOTE Confidence: 0.9910341

01:12:57.139 --> 01:12:58.520
for sharing your

NOTE Confidence: 0.9619288

01:12:59.619 --> 01:13:01.460
your cancer journey. And it

NOTE Confidence: 0.9619288

01:13:01.699 --> 01:13:02.840
you know, I think that

NOTE Confidence: 0.9619288

01:13:03.059 --> 01:13:05.724
it's important that overall survival

NOTE Confidence: 0.9619288

01:13:05.784 --> 01:13:06.604
is not,

NOTE Confidence: 0.99990094

01:13:07.545 --> 01:13:08.045
everything

NOTE Confidence: 0.93973285

01:13:08.425 --> 01:13:10.264
and that that we really

NOTE Confidence: 0.93973285

01:13:10.264 --> 01:13:11.645
have to look at,

NOTE Confidence: 0.9375098

01:13:12.425 --> 01:13:14.045
quality of life. And,

NOTE Confidence: 0.98449373

01:13:14.665 --> 01:13:16.204
I think that the

NOTE Confidence: 0.9958439

01:13:16.880 --> 01:13:18.080
one of the things that

NOTE Confidence: 0.9958439

01:13:18.080 --> 01:13:19.200
that I I do think

NOTE Confidence: 0.9958439

01:13:19.200 --> 01:13:20.640
we do really well here

NOTE Confidence: 0.9958439

01:13:20.640 --> 01:13:22.340
is when things don't go

NOTE Confidence: 0.9983423

01:13:22.640 --> 01:13:24.240
the way that we would

NOTE Confidence: 0.9983423

01:13:24.240 --> 01:13:25.380
love them to go,

NOTE Confidence: 0.9934229

01:13:26.160 --> 01:13:27.140
to, you know,

NOTE Confidence: 0.99983054

01:13:27.760 --> 01:13:29.460
have ways to mitigate

NOTE Confidence: 0.9784275

01:13:30.365 --> 01:13:32.545
complications of treatment. And so,

NOTE Confidence: 0.9869952

01:13:33.405 --> 01:13:34.925
whether it's a recurrent nerve

NOTE Confidence: 0.9869952

01:13:34.925 --> 01:13:36.145
issue and medializing

NOTE Confidence: 0.9139715

01:13:36.525 --> 01:13:37.505
cords or,

NOTE Confidence: 0.9836427

01:13:38.285 --> 01:13:39.165
you know, having, like, a

NOTE Confidence: 0.9836427

01:13:39.165 --> 01:13:41.185
world class ENT team,

NOTE Confidence: 0.7552013

01:13:42.925 --> 01:13:43.425
or,

NOTE Confidence: 0.94898754

01:13:44.285 --> 01:13:46.020
really a great pulmonary team.

NOTE Confidence: 0.94898754

01:13:46.020 --> 01:13:47.300
But but I think your

NOTE Confidence: 0.94898754

01:13:47.300 --> 01:13:48.739
your points are are really

NOTE Confidence: 0.94898754

01:13:48.739 --> 01:13:50.340
well taken. And and I,

NOTE Confidence: 0.94898754

01:13:50.340 --> 01:13:51.159
you know, I

NOTE Confidence: 0.9808472

01:13:51.460 --> 01:13:52.840
I I think I never

NOTE Confidence: 0.9300961

01:13:53.300 --> 01:13:54.739
ever talk anybody into an

NOTE Confidence: 0.9300961

01:13:54.739 --> 01:13:55.239
esophageectomy

NOTE Confidence: 0.98943883

01:13:55.619 --> 01:13:56.820
because it really is a

NOTE Confidence: 0.98943883

01:13:56.820 --> 01:13:58.199
trade off. It's an investment.

NOTE Confidence: 0.965471

01:13:58.945 --> 01:14:00.145
It's and I'm sure you

NOTE Confidence: 0.965471

01:14:00.145 --> 01:14:01.265
could attest. It's a it's

NOTE Confidence: 0.965471

01:14:01.265 --> 01:14:03.205
a it's a tremendous recovery,

NOTE Confidence: 0.9987316

01:14:04.545 --> 01:14:05.985
and that trade off has

NOTE Confidence: 0.9987316

01:14:05.985 --> 01:14:06.885
to be meaningful.

NOTE Confidence: 0.9285773

01:14:07.505 --> 01:14:09.765
The potential gains in survival

NOTE Confidence: 0.9285773

01:14:09.985 --> 01:14:10.800
have to be,

NOTE Confidence: 0.9601652

01:14:11.439 --> 01:14:12.880
meaningful. And and this is

NOTE Confidence: 0.9601652

01:14:12.880 --> 01:14:14.479
a you know, I've had

NOTE Confidence: 0.9601652

01:14:14.479 --> 01:14:16.239
several patients in their late

NOTE Confidence: 0.9601652

01:14:16.239 --> 01:14:16.739
twenties,

NOTE Confidence: 0.975209

01:14:18.079 --> 01:14:18.579
and,

NOTE Confidence: 0.9764377

01:14:19.040 --> 01:14:19.920
but but a lot of

NOTE Confidence: 0.9764377

01:14:19.920 --> 01:14:21.599
our patients are in their

NOTE Confidence: 0.9764377

01:14:21.599 --> 01:14:23.199
eighties and are facing this.

NOTE Confidence: 0.9764377

01:14:23.199 --> 01:14:24.559
So you have both ends

NOTE Confidence: 0.9764377

01:14:24.559 --> 01:14:25.920
of the spectrum and trying

NOTE Confidence: 0.9764377

01:14:25.920 --> 01:14:26.579
to really

NOTE Confidence: 0.9998686

01:14:27.255 --> 01:14:28.235
be transparent

NOTE Confidence: 0.9998349

01:14:28.614 --> 01:14:29.114
about

NOTE Confidence: 0.99172115

01:14:29.814 --> 01:14:31.034
what is the potential,

NOTE Confidence: 0.99988556

01:14:31.895 --> 01:14:32.554
to gain

NOTE Confidence: 0.93710667

01:14:33.175 --> 01:14:33.655
from,

NOTE Confidence: 0.9987374

01:14:34.135 --> 01:14:36.074
each modality of treatment,

NOTE Confidence: 0.9955937

01:14:37.175 --> 01:14:37.675
including

NOTE Confidence: 0.95339805

01:14:38.054 --> 01:14:40.455
systemic treatment and radiation and

NOTE Confidence: 0.95339805

01:14:40.455 --> 01:14:40.955
surgery,

NOTE Confidence: 0.9537811

01:14:42.310 --> 01:14:43.930
and what is the likelihood

NOTE Confidence: 0.9991208

01:14:44.390 --> 01:14:46.469
of experiencing an event that

NOTE Confidence: 0.9991208

01:14:46.469 --> 01:14:46.969
degrades

NOTE Confidence: 0.9735679

01:14:47.270 --> 01:14:48.330
quality of life?

NOTE Confidence: 0.98614335

01:14:51.590 --> 01:14:53.510
Yeah. I'll I'll follow,

NOTE Confidence: 0.8614213

01:14:53.989 --> 01:14:55.610
doctor Boffa's radiation

NOTE Confidence: 0.9989146

01:14:56.545 --> 01:14:57.045
generally

NOTE Confidence: 0.87581575

01:14:57.665 --> 01:14:59.345
follows surgery, but, the,

NOTE Confidence: 0.9971585

01:15:00.145 --> 01:15:01.525
this is something where,

NOTE Confidence: 0.932918

01:15:02.145 --> 01:15:03.125
miss Karki,

NOTE Confidence: 0.94049364

01:15:03.585 --> 01:15:04.625
you know, this is really,

NOTE Confidence: 0.94049364

01:15:05.104 --> 01:15:06.625
an amazing story, and thank

NOTE Confidence: 0.94049364

01:15:06.625 --> 01:15:07.825
you so much for sharing.

NOTE Confidence: 0.94049364

01:15:07.825 --> 01:15:08.325
Congratulations

NOTE Confidence: 0.9952904

01:15:09.025 --> 01:15:10.485
on on your fourth anniversary

NOTE Confidence: 0.93691206

01:15:11.025 --> 01:15:12.610
of of of being cancer

NOTE Confidence: 0.93691206

01:15:12.610 --> 01:15:13.110
free.

NOTE Confidence: 0.8929612

01:15:13.650 --> 01:15:14.790
It's really amazing.

NOTE Confidence: 0.9709115

01:15:15.410 --> 01:15:16.710
I I share,

NOTE Confidence: 0.9754405

01:15:17.890 --> 01:15:18.850
a lot of what you

NOTE Confidence: 0.9754405

01:15:18.850 --> 01:15:20.210
say where, you know, I

NOTE Confidence: 0.9754405

01:15:20.370 --> 01:15:21.410
when I walk in and

NOTE Confidence: 0.9754405

01:15:21.410 --> 01:15:23.570
talk to, patients in the

NOTE Confidence: 0.9754405

01:15:23.570 --> 01:15:24.070
room,

NOTE Confidence: 0.9619093

01:15:25.465 --> 01:15:27.145
I I do try to

NOTE Confidence: 0.9619093

01:15:27.145 --> 01:15:27.645
really

NOTE Confidence: 0.99927974

01:15:27.945 --> 01:15:29.545
take into account and try

NOTE Confidence: 0.99927974

01:15:29.545 --> 01:15:31.225
to figure out what the

NOTE Confidence: 0.99927974

01:15:31.225 --> 01:15:32.685
right treatment is for them.

NOTE Confidence: 0.9976883

01:15:32.985 --> 01:15:34.925
Radiation is a difficult treatment.

NOTE Confidence: 0.9976883

01:15:34.985 --> 01:15:36.104
It's a it's a lengthy

NOTE Confidence: 0.9976883

01:15:36.104 --> 01:15:36.604
treatment.

NOTE Confidence: 0.9609415

01:15:37.145 --> 01:15:38.585
You know, there's a lot

NOTE Confidence: 0.9609415

01:15:38.585 --> 01:15:38.745
of,

NOTE Confidence: 0.9920557

01:15:40.460 --> 01:15:42.000
side effects that are associated

NOTE Confidence: 0.9920557

01:15:42.060 --> 01:15:43.760
with radiation to the esophagus.

NOTE Confidence: 0.9157795

01:15:44.620 --> 01:15:44.939
And,

NOTE Confidence: 0.93140405

01:15:45.500 --> 01:15:47.179
and and, and so it

NOTE Confidence: 0.93140405

01:15:47.179 --> 01:15:48.939
really is not, the the

NOTE Confidence: 0.93140405

01:15:48.939 --> 01:15:50.239
right treatment for everybody.

NOTE Confidence: 0.9697584

01:15:50.860 --> 01:15:51.360
However,

NOTE Confidence: 0.93518037

01:15:51.739 --> 01:15:53.515
you know, in overall, we

NOTE Confidence: 0.93518037

01:15:53.515 --> 01:15:54.875
try to assemble a treatment

NOTE Confidence: 0.93518037

01:15:54.875 --> 01:15:56.075
package that is,

NOTE Confidence: 0.9893793

01:15:56.955 --> 01:15:58.575
that combines the best

NOTE Confidence: 0.7817507

01:16:00.715 --> 01:16:02.095
chances of success

NOTE Confidence: 0.9969849

01:16:03.275 --> 01:16:04.955
together with trying to figure

NOTE Confidence: 0.9969849

01:16:04.955 --> 01:16:05.915
out what's best for the

NOTE Confidence: 0.9969849

01:16:05.915 --> 01:16:07.375
patient's quality of life

NOTE Confidence: 0.99732196

01:16:07.810 --> 01:16:08.550
going forward.

NOTE Confidence: 0.9812358

01:16:09.490 --> 01:16:11.090
We need better treatments. That's

NOTE Confidence: 0.9812358

01:16:11.090 --> 01:16:11.750
for sure.

NOTE Confidence: 0.99609184

01:16:12.210 --> 01:16:13.810
So that's where the research

NOTE Confidence: 0.99609184

01:16:13.810 --> 01:16:14.310
that,

NOTE Confidence: 0.92579395

01:16:14.689 --> 01:16:17.010
doctor Raghav is, Sundar is

NOTE Confidence: 0.92579395

01:16:17.010 --> 01:16:18.550
talking about are so important,

NOTE Confidence: 0.9652001

01:16:19.170 --> 01:16:20.870
novel novel therapies.

NOTE Confidence: 0.93995297

01:16:21.435 --> 01:16:22.735
You know, proton therapy,

NOTE Confidence: 0.9886974

01:16:23.035 --> 01:16:24.555
I'm really sorry to hear

NOTE Confidence: 0.9886974

01:16:24.555 --> 01:16:26.155
that your your lungs were

NOTE Confidence: 0.9886974

01:16:26.155 --> 01:16:27.775
impacted by the treatments.

NOTE Confidence: 0.99883807

01:16:28.314 --> 01:16:29.354
You know, I think that's

NOTE Confidence: 0.99883807

01:16:29.354 --> 01:16:31.595
a big advantage of newer

NOTE Confidence: 0.99883807

01:16:31.595 --> 01:16:32.095
radiation

NOTE Confidence: 0.94718647

01:16:32.795 --> 01:16:35.215
therapies like proton therapy, which,

NOTE Confidence: 0.94718647

01:16:35.490 --> 01:16:37.189
you know, patients don't have

NOTE Confidence: 0.95805955

01:16:38.130 --> 01:16:39.729
may have only limited access

NOTE Confidence: 0.95805955

01:16:39.729 --> 01:16:41.010
to. You know, protons are

NOTE Confidence: 0.95805955

01:16:41.010 --> 01:16:41.750
not everywhere.

NOTE Confidence: 0.9488009

01:16:42.930 --> 01:16:43.729
And but,

NOTE Confidence: 0.9438608

01:16:44.210 --> 01:16:46.210
but, has been demonstrated really

NOTE Confidence: 0.9438608

01:16:46.210 --> 01:16:48.210
to reduce the dose to

NOTE Confidence: 0.9438608

01:16:48.210 --> 01:16:49.330
the to the lungs and

NOTE Confidence: 0.9438608

01:16:49.330 --> 01:16:50.530
the heart as as I

NOTE Confidence: 0.9438608

01:16:50.530 --> 01:16:51.030
was

NOTE Confidence: 0.99673533

01:16:51.465 --> 01:16:52.285
showing earlier.

NOTE Confidence: 0.8742898

01:16:53.305 --> 01:16:53.545
But,

NOTE Confidence: 0.94864064

01:16:54.745 --> 01:16:56.104
that being said, I'm so

NOTE Confidence: 0.94864064

01:16:56.104 --> 01:16:57.165
glad that you're

NOTE Confidence: 0.9175957

01:16:58.425 --> 01:17:00.905
doing well after treatment and,

NOTE Confidence: 0.9229301

01:17:01.385 --> 01:17:03.385
you know, and and at

NOTE Confidence: 0.9229301

01:17:03.385 --> 01:17:04.685
a at a great place

NOTE Confidence: 0.83831364

01:17:05.385 --> 01:17:06.205
down in Florida,

NOTE Confidence: 0.99147904

01:17:06.860 --> 01:17:08.860
you know, pursuing pursuing things

NOTE Confidence: 0.99147904

01:17:08.860 --> 01:17:10.240
that are important to you.

NOTE Confidence: 0.99147904

01:17:10.460 --> 01:17:11.520
Thank you for sharing.

NOTE Confidence: 0.9955519

01:17:13.180 --> 01:17:13.680
Thanks,

NOTE Confidence: 0.93681914

01:17:14.140 --> 01:17:15.900
doctor Du. I I have

NOTE Confidence: 0.93681914

01:17:15.900 --> 01:17:17.580
a question to doctor Gibson

NOTE Confidence: 0.93681914

01:17:17.580 --> 01:17:19.260
as well as to, Deepika

NOTE Confidence: 0.93681914

01:17:19.260 --> 01:17:19.760
because,

NOTE Confidence: 0.97218275

01:17:21.375 --> 01:17:23.454
if, Deepika, you shared your

NOTE Confidence: 0.97218275

01:17:23.454 --> 01:17:24.735
your your case report with

NOTE Confidence: 0.97218275

01:17:24.735 --> 01:17:25.854
us, and you actually achieved

NOTE Confidence: 0.97218275

01:17:25.854 --> 01:17:27.635
a pathological complete response.

NOTE Confidence: 0.9834098

01:17:28.175 --> 01:17:30.275
So my question is,

NOTE Confidence: 0.89560384

01:17:31.775 --> 01:17:33.554
to to Deepika will be

NOTE Confidence: 0.96091133

01:17:34.400 --> 01:17:35.920
at that point where you

NOTE Confidence: 0.96091133

01:17:35.920 --> 01:17:37.139
had to make the judgment

NOTE Confidence: 0.96091133

01:17:37.280 --> 01:17:38.639
call, you would have been

NOTE Confidence: 0.96091133

01:17:38.639 --> 01:17:41.119
peri clinical complete response. And

NOTE Confidence: 0.96091133

01:17:41.119 --> 01:17:42.719
so the decision to still

NOTE Confidence: 0.96091133

01:17:42.719 --> 01:17:44.079
go ahead with surgery to

NOTE Confidence: 0.96091133

01:17:44.079 --> 01:17:45.199
be really sure that you

NOTE Confidence: 0.96091133

01:17:45.199 --> 01:17:46.739
have no disease left behind,

NOTE Confidence: 0.96091133

01:17:46.814 --> 01:17:47.935
I wanna hear your thoughts

NOTE Confidence: 0.96091133

01:17:47.935 --> 01:17:49.555
on the journey. And separately

NOTE Confidence: 0.97512054

01:17:49.935 --> 01:17:51.555
to, doctor Gibson is,

NOTE Confidence: 0.98671234

01:17:52.415 --> 01:17:54.175
how much of discordance do

NOTE Confidence: 0.98671234

01:17:54.175 --> 01:17:54.755
you see

NOTE Confidence: 0.9831087

01:17:55.055 --> 01:17:57.215
between CCR and PCR? Because

NOTE Confidence: 0.9831087

01:17:57.215 --> 01:17:58.255
that's always gonna be this

NOTE Confidence: 0.9831087

01:17:58.255 --> 01:17:59.535
judgment call when we try

NOTE Confidence: 0.9831087

01:17:59.535 --> 01:18:00.755
to head down this nonoperative

NOTE Confidence: 0.95553863

01:18:01.055 --> 01:18:02.275
route. And

NOTE Confidence: 0.99947375

01:18:03.600 --> 01:18:05.219
do we always need to

NOTE Confidence: 0.94302624

01:18:05.840 --> 01:18:07.280
get PCR for us to

NOTE Confidence: 0.94302624

01:18:07.280 --> 01:18:08.560
be confident that we've gotten

NOTE Confidence: 0.94302624

01:18:08.560 --> 01:18:10.000
rid of everything, or is

NOTE Confidence: 0.94302624

01:18:10.000 --> 01:18:11.040
CCR good enough? I mean,

NOTE Confidence: 0.94302624

01:18:11.040 --> 01:18:12.080
doctor Buffa spoke a little

NOTE Confidence: 0.94302624

01:18:12.080 --> 01:18:12.800
bit about it, but I'd

NOTE Confidence: 0.94302624

01:18:12.800 --> 01:18:14.000
like to hear your thoughts

NOTE Confidence: 0.94302624

01:18:14.000 --> 01:18:15.280
on this. Maybe we'll hear

NOTE Confidence: 0.94302624

01:18:15.280 --> 01:18:16.560
doctor Gibson's thoughts as and

NOTE Confidence: 0.94302624

01:18:16.560 --> 01:18:18.645
then listen to what Deepika

NOTE Confidence: 0.94302624

01:18:18.645 --> 01:18:19.784
had to think about. Sure.

NOTE Confidence: 0.9824874

01:18:21.525 --> 01:18:22.885
Yeah. I also wanna say

NOTE Confidence: 0.9824874

01:18:22.885 --> 01:18:24.585
thank you to, to Deepika

NOTE Confidence: 0.9824874

01:18:24.645 --> 01:18:25.685
for sharing her story. I

NOTE Confidence: 0.9824874

01:18:25.685 --> 01:18:26.244
think it's,

NOTE Confidence: 0.98450214

01:18:26.645 --> 01:18:28.324
it's incredible to hear these,

NOTE Confidence: 0.975283

01:18:29.910 --> 01:18:31.850
these real life experiences,

NOTE Confidence: 0.99594665

01:18:32.310 --> 01:18:33.910
and it really paints a

NOTE Confidence: 0.99594665

01:18:33.910 --> 01:18:35.830
picture of of what people

NOTE Confidence: 0.99594665

01:18:35.830 --> 01:18:36.489
go through

NOTE Confidence: 0.9740044

01:18:36.870 --> 01:18:38.410
when I sign that report,

NOTE Confidence: 0.99442774

01:18:38.949 --> 01:18:40.489
that there's, you know, cancer

NOTE Confidence: 0.99442774

01:18:40.550 --> 01:18:41.050
found.

NOTE Confidence: 0.9324438

01:18:42.710 --> 01:18:43.770
I think for

NOTE Confidence: 0.95855963

01:18:44.835 --> 01:18:46.595
you know, I I

NOTE Confidence: 0.9822429

01:18:47.235 --> 01:18:48.354
it's actually a really good

NOTE Confidence: 0.9822429

01:18:48.354 --> 01:18:49.735
question, you know, clinical,

NOTE Confidence: 0.988012

01:18:50.195 --> 01:18:52.195
complete clinical response versus complete

NOTE Confidence: 0.988012

01:18:52.195 --> 01:18:53.335
pathological response.

NOTE Confidence: 0.9983182

01:18:55.395 --> 01:18:56.135
I actually

NOTE Confidence: 0.9927437

01:18:56.850 --> 01:18:58.530
don't have a study on

NOTE Confidence: 0.9927437

01:18:58.530 --> 01:18:59.650
the off the top of

NOTE Confidence: 0.9927437

01:18:59.650 --> 01:19:01.489
my head that, sort of

NOTE Confidence: 0.9927437

01:19:01.489 --> 01:19:03.330
looked into that. We are

NOTE Confidence: 0.9927437

01:19:03.330 --> 01:19:05.489
not following that as a,

NOTE Confidence: 0.9949651

01:19:07.409 --> 01:19:08.150
as a

NOTE Confidence: 0.6328612

01:19:08.530 --> 01:19:09.030
metric,

NOTE Confidence: 0.9159984

01:19:09.445 --> 01:19:10.245
at Yale that I know

NOTE Confidence: 0.9159984

01:19:10.245 --> 01:19:11.845
of unless doctor Baffa has

NOTE Confidence: 0.9159984

01:19:11.845 --> 01:19:12.825
something that,

NOTE Confidence: 0.982456

01:19:13.765 --> 01:19:15.604
his group, is doing. So

NOTE Confidence: 0.982456

01:19:15.604 --> 01:19:16.645
I actually think it would

NOTE Confidence: 0.982456

01:19:16.645 --> 01:19:17.045
be,

NOTE Confidence: 0.99952453

01:19:17.525 --> 01:19:19.365
interesting to, you know, look

NOTE Confidence: 0.99952453

01:19:19.365 --> 01:19:20.485
into that a little bit

NOTE Confidence: 0.99952453

01:19:20.485 --> 01:19:20.985
more.

NOTE Confidence: 0.9694653

01:19:23.900 --> 01:19:25.179
I I will I will

NOTE Confidence: 0.9694653

01:19:25.179 --> 01:19:27.420
say that complete pathological response

NOTE Confidence: 0.9694653

01:19:27.420 --> 01:19:28.560
is not a simple,

NOTE Confidence: 0.9804735

01:19:30.860 --> 01:19:32.239
concept. I think,

NOTE Confidence: 0.98827255

01:19:33.179 --> 01:19:34.939
I would encourage anybody who

NOTE Confidence: 0.98827255

01:19:34.939 --> 01:19:36.880
reads papers that evaluate that

NOTE Confidence: 0.98827255

01:19:37.100 --> 01:19:38.800
to understand how exactly

NOTE Confidence: 0.9951357

01:19:39.795 --> 01:19:40.535
the esophagus

NOTE Confidence: 0.9684067

01:19:41.155 --> 01:19:42.375
resections were,

NOTE Confidence: 0.9958285

01:19:42.835 --> 01:19:43.335
examined.

NOTE Confidence: 0.950832

01:19:43.955 --> 01:19:46.114
And when we examine post

NOTE Confidence: 0.950832

01:19:46.114 --> 01:19:47.175
treatment esophagectomy

NOTE Confidence: 0.99701583

01:19:47.475 --> 01:19:47.975
specimen,

NOTE Confidence: 0.9844911

01:19:48.675 --> 01:19:50.035
we have a protocol where

NOTE Confidence: 0.9844911

01:19:50.035 --> 01:19:51.875
we examine the entire tumor

NOTE Confidence: 0.9844911

01:19:51.875 --> 01:19:52.775
bed histologically,

NOTE Confidence: 0.98966765

01:19:54.100 --> 01:19:55.699
and that can sometimes be

NOTE Confidence: 0.98966765

01:19:55.699 --> 01:19:56.979
really difficult to tell. So

NOTE Confidence: 0.98966765

01:19:56.979 --> 01:19:58.180
we end up submitting, you

NOTE Confidence: 0.98966765

01:19:58.180 --> 01:19:59.699
know, the entire area where

NOTE Confidence: 0.98966765

01:19:59.699 --> 01:20:01.160
the tumor might have been,

NOTE Confidence: 0.9956907

01:20:01.780 --> 01:20:02.920
if we can't identify,

NOTE Confidence: 0.9911916

01:20:03.699 --> 01:20:04.820
a a good tumor bed.

NOTE Confidence: 0.9911916

01:20:04.820 --> 01:20:06.280
So we're, you know, doing

NOTE Confidence: 0.9911916

01:20:06.340 --> 01:20:07.400
a complete assessment

NOTE Confidence: 0.9542267

01:20:07.780 --> 01:20:08.260
of that,

NOTE Confidence: 0.9901445

01:20:09.785 --> 01:20:11.165
of the tumor site.

NOTE Confidence: 0.9675174

01:20:11.865 --> 01:20:13.785
And I would say there's

NOTE Confidence: 0.9675174

01:20:13.785 --> 01:20:14.285
not,

NOTE Confidence: 0.9882247

01:20:16.985 --> 01:20:18.345
you know, depending on where

NOTE Confidence: 0.9882247

01:20:18.345 --> 01:20:19.005
you practice,

NOTE Confidence: 0.9406811

01:20:19.305 --> 01:20:20.365
that might be different.

NOTE Confidence: 0.99730873

01:20:20.905 --> 01:20:22.205
There might be different approaches

NOTE Confidence: 0.99730873

01:20:22.345 --> 01:20:24.670
of how pathology is assessed.

NOTE Confidence: 0.9970091

01:20:25.050 --> 01:20:26.110
And so I think

NOTE Confidence: 0.9958202

01:20:26.969 --> 01:20:28.010
before you sort of look

NOTE Confidence: 0.9958202

01:20:28.010 --> 01:20:28.810
at a paper and look

NOTE Confidence: 0.9958202

01:20:28.810 --> 01:20:30.650
at the pathologic complete response

NOTE Confidence: 0.9958202

01:20:30.650 --> 01:20:31.949
data, understanding

NOTE Confidence: 0.9973249

01:20:32.250 --> 01:20:33.530
what the protocol was to

NOTE Confidence: 0.9973249

01:20:33.530 --> 01:20:35.050
examine the esophagus is an

NOTE Confidence: 0.9973249

01:20:35.050 --> 01:20:35.550
extremely

NOTE Confidence: 0.895017

01:20:36.010 --> 01:20:37.229
important exercise,

NOTE Confidence: 0.9992131

01:20:38.195 --> 01:20:39.235
because if they did not

NOTE Confidence: 0.9992131

01:20:39.235 --> 01:20:41.255
examine the entire tumor bed,

NOTE Confidence: 0.9617583

01:20:43.235 --> 01:20:44.114
you know, they might have

NOTE Confidence: 0.9617583

01:20:44.114 --> 01:20:45.314
missed that residual bit of

NOTE Confidence: 0.9617583

01:20:45.314 --> 01:20:46.835
cancer that was in there.

NOTE Confidence: 0.9617583

01:20:46.835 --> 01:20:48.034
And we see that. We

NOTE Confidence: 0.9617583

01:20:48.034 --> 01:20:48.994
see that. We we will

NOTE Confidence: 0.9617583

01:20:48.994 --> 01:20:50.434
submit an entire tumor bed,

NOTE Confidence: 0.9617583

01:20:50.434 --> 01:20:51.715
you know, let's say a

NOTE Confidence: 0.9617583

01:20:51.715 --> 01:20:53.580
three centimeter scar at, you

NOTE Confidence: 0.9617583

01:20:53.580 --> 01:20:55.119
know, above the g junction.

NOTE Confidence: 0.98672324

01:20:55.820 --> 01:20:57.340
We'll submit that, examine that

NOTE Confidence: 0.98672324

01:20:57.340 --> 01:20:58.780
in, you know, fifteen, twenty

NOTE Confidence: 0.98672324

01:20:58.780 --> 01:21:00.400
blocks, and there'll be cancer

NOTE Confidence: 0.98672324

01:21:00.460 --> 01:21:01.260
on one or two of

NOTE Confidence: 0.98672324

01:21:01.260 --> 01:21:01.760
them

NOTE Confidence: 0.97987664

01:21:02.540 --> 01:21:03.659
and not the rest. And

NOTE Confidence: 0.97987664

01:21:03.659 --> 01:21:05.099
so you really could miss

NOTE Confidence: 0.97987664

01:21:05.099 --> 01:21:05.900
it if you're not doing

NOTE Confidence: 0.97987664

01:21:05.900 --> 01:21:07.215
a complete pathologic response. So

NOTE Confidence: 0.97987664

01:21:07.215 --> 01:21:09.135
that's my one cautionary tale

NOTE Confidence: 0.97987664

01:21:09.135 --> 01:21:09.955
about that

NOTE Confidence: 0.9775854

01:21:10.335 --> 01:21:11.955
and data about that.

NOTE Confidence: 0.97832614

01:21:12.335 --> 01:21:14.014
But, yeah, I I don't

NOTE Confidence: 0.97832614

01:21:14.014 --> 01:21:15.054
I don't know the data

NOTE Confidence: 0.97832614

01:21:15.054 --> 01:21:15.955
offhand comparing

NOTE Confidence: 0.98546475

01:21:16.335 --> 01:21:18.494
the clinical versus pathological response.

NOTE Confidence: 0.99913865

01:21:18.814 --> 01:21:19.854
So that's something I would

NOTE Confidence: 0.99913865

01:21:19.854 --> 01:21:20.514
need to

NOTE Confidence: 0.9834376

01:21:21.250 --> 01:21:22.210
look into a little bit

NOTE Confidence: 0.9834376

01:21:22.210 --> 01:21:22.710
more.

NOTE Confidence: 0.97195977

01:21:23.330 --> 01:21:24.130
And I don't know if

NOTE Confidence: 0.97195977

01:21:24.130 --> 01:21:25.270
anybody else has,

NOTE Confidence: 0.93105537

01:21:26.610 --> 01:21:27.810
insight into that. I bet

NOTE Confidence: 0.93105537

01:21:27.889 --> 01:21:29.090
I'm sure Dan has some

NOTE Confidence: 0.93105537

01:21:29.090 --> 01:21:30.369
insight or, Kevin, I see

NOTE Confidence: 0.93105537

01:21:30.369 --> 01:21:31.889
you unmuted as well. I

NOTE Confidence: 0.93105537

01:21:31.889 --> 01:21:32.929
think you can flip a

NOTE Confidence: 0.93105537

01:21:32.929 --> 01:21:33.429
coin

NOTE Confidence: 0.7413661

01:21:33.810 --> 01:21:35.750
with a a complete response,

NOTE Confidence: 0.7413661

01:21:35.889 --> 01:21:36.130
and,

NOTE Confidence: 0.9709976

01:21:37.145 --> 01:21:38.665
and that'll be about as

NOTE Confidence: 0.9709976

01:21:38.665 --> 01:21:39.545
good as any,

NOTE Confidence: 0.8765298

01:21:40.265 --> 01:21:40.765
anything.

NOTE Confidence: 0.9789843

01:21:41.705 --> 01:21:43.485
To Dan's point, I think

NOTE Confidence: 0.9789843

01:21:43.705 --> 01:21:45.945
we we absolutely need better

NOTE Confidence: 0.9789843

01:21:45.945 --> 01:21:47.005
ways of assessing,

NOTE Confidence: 0.77982044

01:21:48.265 --> 01:21:49.725
such as circulating,

NOTE Confidence: 0.9425833

01:21:50.344 --> 01:21:51.989
you know, blood test, tumor

NOTE Confidence: 0.9425833

01:21:51.989 --> 01:21:54.010
markers, or, you know, even

NOTE Confidence: 0.9425833

01:21:54.309 --> 01:21:55.210
AI approaches.

NOTE Confidence: 0.9962432

01:21:55.909 --> 01:21:57.269
That's really the the most

NOTE Confidence: 0.9962432

01:21:57.269 --> 01:21:58.250
important question

NOTE Confidence: 0.93655515

01:21:58.630 --> 01:21:59.449
with chemoradiation

NOTE Confidence: 0.62604386

01:22:00.309 --> 01:22:00.789
and,

NOTE Confidence: 0.9738174

01:22:01.269 --> 01:22:02.789
these days, I think, and

NOTE Confidence: 0.9738174

01:22:02.789 --> 01:22:04.170
something which could really

NOTE Confidence: 0.99618423

01:22:05.915 --> 01:22:06.415
revolutionize

NOTE Confidence: 0.9951118

01:22:06.715 --> 01:22:07.915
the the field, I think,

NOTE Confidence: 0.9951118

01:22:07.915 --> 01:22:09.275
and really improve our patient

NOTE Confidence: 0.9951118

01:22:09.275 --> 01:22:09.775
care.

NOTE Confidence: 0.9930099

01:22:11.354 --> 01:22:12.395
Yeah. I I agree with

NOTE Confidence: 0.9930099

01:22:12.395 --> 01:22:14.315
that. It's it's about there's

NOTE Confidence: 0.9930099

01:22:14.315 --> 01:22:16.315
about a fifty percent false

NOTE Confidence: 0.9930099

01:22:16.315 --> 01:22:17.935
negative rate to the clinical

NOTE Confidence: 0.9179543

01:22:18.235 --> 01:22:20.330
evaluation. That is really what

NOTE Confidence: 0.9179543

01:22:20.390 --> 01:22:22.410
presaino showed. That's what,

NOTE Confidence: 0.93091786

01:22:23.430 --> 01:22:24.330
we'd found,

NOTE Confidence: 0.9108674

01:22:25.270 --> 01:22:25.770
when

NOTE Confidence: 0.9723387

01:22:26.070 --> 01:22:27.590
I was in Cleveland, and

NOTE Confidence: 0.9723387

01:22:27.590 --> 01:22:29.450
it's it's a pretty consistent,

NOTE Confidence: 0.9821565

01:22:30.229 --> 01:22:30.729
thing.

NOTE Confidence: 0.9956912

01:22:31.030 --> 01:22:32.070
But we know that not

NOTE Confidence: 0.9956912

01:22:32.070 --> 01:22:33.130
every pathologic

NOTE Confidence: 0.9848079

01:22:33.590 --> 01:22:35.325
complete responder is cured.

NOTE Confidence: 0.99224997

01:22:36.125 --> 01:22:37.245
So it's it's,

NOTE Confidence: 0.8292417

01:22:38.925 --> 01:22:39.985
but but the

NOTE Confidence: 0.98055494

01:22:40.445 --> 01:22:41.965
Joanna, that's a really interesting

NOTE Confidence: 0.98055494

01:22:41.965 --> 01:22:43.005
point that I didn't really

NOTE Confidence: 0.98055494

01:22:43.005 --> 01:22:44.225
think about is how,

NOTE Confidence: 0.9653612

01:22:45.645 --> 01:22:47.485
the processing does you know,

NOTE Confidence: 0.9653612

01:22:47.485 --> 01:22:48.445
I you know, you're

NOTE Confidence: 0.97405446

01:22:50.100 --> 01:22:51.300
nobody likes to look for

NOTE Confidence: 0.97405446

01:22:51.300 --> 01:22:52.760
things they don't wanna find.

NOTE Confidence: 0.9979857

01:22:53.060 --> 01:22:53.560
And,

NOTE Confidence: 0.9917455

01:22:54.020 --> 01:22:55.139
you know, it it's,

NOTE Confidence: 0.97376543

01:22:56.179 --> 01:22:57.460
it is interesting to know

NOTE Confidence: 0.97376543

01:22:57.540 --> 01:22:59.139
understand the different processing. That

NOTE Confidence: 0.97376543

01:22:59.139 --> 01:23:00.340
would be an interesting study

NOTE Confidence: 0.97376543

01:23:00.340 --> 01:23:01.860
is to sort of look

NOTE Confidence: 0.97376543

01:23:01.860 --> 01:23:03.800
at complete pathologic responders,

NOTE Confidence: 0.9917289

01:23:04.955 --> 01:23:06.875
have different centers look at

NOTE Confidence: 0.9917289

01:23:06.875 --> 01:23:07.995
the same things to see

NOTE Confidence: 0.9917289

01:23:07.995 --> 01:23:09.675
if there's concordance in that.

NOTE Confidence: 0.9917289

01:23:09.675 --> 01:23:10.875
But I think just looking

NOTE Confidence: 0.9917289

01:23:10.875 --> 01:23:12.075
at the protocols and sort

NOTE Confidence: 0.9917289

01:23:12.075 --> 01:23:13.595
of understanding how people are

NOTE Confidence: 0.9917289

01:23:13.595 --> 01:23:14.095
assessing

NOTE Confidence: 0.9276007

01:23:14.475 --> 01:23:14.955
that,

NOTE Confidence: 0.9563937

01:23:15.995 --> 01:23:17.275
that point, I think, would

NOTE Confidence: 0.9563937

01:23:17.275 --> 01:23:18.575
be interesting. Yep.

NOTE Confidence: 0.9951438

01:23:21.939 --> 01:23:24.100
And just on that note,

NOTE Confidence: 0.9951438

01:23:24.100 --> 01:23:24.979
you can see that a

NOTE Confidence: 0.9951438

01:23:24.979 --> 01:23:26.260
new study is forming at

NOTE Confidence: 0.9951438

01:23:26.260 --> 01:23:27.159
the end of this

NOTE Confidence: 0.65662575

01:23:27.780 --> 01:23:28.280
with

NOTE Confidence: 0.9292027

01:23:28.820 --> 01:23:29.560
this group.

NOTE Confidence: 0.9314238

01:23:30.260 --> 01:23:31.060
But I I mean, I

NOTE Confidence: 0.9314238

01:23:31.060 --> 01:23:32.100
also want to highlight the

NOTE Confidence: 0.9314238

01:23:32.100 --> 01:23:33.405
fact that we are very,

NOTE Confidence: 0.9314238

01:23:33.405 --> 01:23:34.865
very dependent on the pathologist

NOTE Confidence: 0.9314238

01:23:35.085 --> 01:23:37.085
for our decision making. So

NOTE Confidence: 0.9314238

01:23:37.085 --> 01:23:38.445
we're very grateful to having

NOTE Confidence: 0.9314238

01:23:38.445 --> 01:23:39.885
a very strong and collaborative

NOTE Confidence: 0.9314238

01:23:39.885 --> 01:23:41.645
pathology team at Yale that

NOTE Confidence: 0.9314238

01:23:41.645 --> 01:23:42.525
helps us make a lot

NOTE Confidence: 0.9314238

01:23:42.525 --> 01:23:43.825
of these decisions downstream.

NOTE Confidence: 0.99357486

01:23:45.085 --> 01:23:46.604
Deepika, are you unmuted? Can

NOTE Confidence: 0.99357486

01:23:46.604 --> 01:23:48.465
you share your thoughts on

NOTE Confidence: 0.99357486

01:23:48.660 --> 01:23:49.400
going for

NOTE Confidence: 0.8117706

01:23:49.860 --> 01:23:51.080
surgery? Hello?

NOTE Confidence: 0.7811075

01:23:51.540 --> 01:23:52.740
Is he here? Yeah. Yeah.

NOTE Confidence: 0.7811075

01:23:52.740 --> 01:23:53.240
I'm

NOTE Confidence: 0.9960175

01:23:53.780 --> 01:23:54.900
so sorry. I always do

NOTE Confidence: 0.9960175

01:23:54.900 --> 01:23:56.340
the voice test before I

NOTE Confidence: 0.9960175

01:23:56.340 --> 01:23:56.840
speak.

NOTE Confidence: 0.8988762

01:23:57.300 --> 01:23:58.500
So, yeah, as as for

NOTE Confidence: 0.8988762

01:23:58.500 --> 01:23:59.540
me, it was like after

NOTE Confidence: 0.8988762

01:23:59.540 --> 01:24:00.200
I finished

NOTE Confidence: 0.9940662

01:24:01.060 --> 01:24:02.740
my treatment with chemo and

NOTE Confidence: 0.9940662

01:24:02.740 --> 01:24:03.800
radio, my

NOTE Confidence: 0.96387595

01:24:04.445 --> 01:24:06.465
surgeon, he performed an endoscopy

NOTE Confidence: 0.96387595

01:24:06.525 --> 01:24:07.185
on me.

NOTE Confidence: 0.9784242

01:24:07.564 --> 01:24:08.765
And on that, he found

NOTE Confidence: 0.9784242

01:24:08.765 --> 01:24:09.425
a polyp.

NOTE Confidence: 0.9960694

01:24:09.885 --> 01:24:11.245
And I was actually, like,

NOTE Confidence: 0.9960694

01:24:11.245 --> 01:24:13.005
clinically well ever since my

NOTE Confidence: 0.9960694

01:24:13.005 --> 01:24:13.505
first

NOTE Confidence: 0.9711915

01:24:13.965 --> 01:24:15.485
dose, like, my first session

NOTE Confidence: 0.9711915

01:24:15.485 --> 01:24:17.085
of chemotherapy. So there was,

NOTE Confidence: 0.9711915

01:24:17.085 --> 01:24:18.800
like, never a question of

NOTE Confidence: 0.9711915

01:24:18.800 --> 01:24:20.500
not being a clinical responder.

NOTE Confidence: 0.97486013

01:24:21.280 --> 01:24:22.320
But when he found that

NOTE Confidence: 0.97486013

01:24:22.320 --> 01:24:22.820
polypony

NOTE Confidence: 0.994848

01:24:23.120 --> 01:24:24.180
follow-up endoscopy

NOTE Confidence: 0.9674077

01:24:24.960 --> 01:24:26.560
and considering my age, like,

NOTE Confidence: 0.9674077

01:24:26.560 --> 01:24:27.380
he kind of

NOTE Confidence: 0.8309182

01:24:27.840 --> 01:24:29.460
counseled me and my family

NOTE Confidence: 0.8309182

01:24:29.520 --> 01:24:30.320
for his of a check

NOTE Confidence: 0.8309182

01:24:30.320 --> 01:24:31.140
to me. And,

NOTE Confidence: 0.90590686

01:24:31.760 --> 01:24:32.880
yeah, that's I think how

NOTE Confidence: 0.90590686

01:24:32.880 --> 01:24:34.675
I how I, like, cave

NOTE Confidence: 0.90590686

01:24:34.675 --> 01:24:35.415
into it.

NOTE Confidence: 0.992328

01:24:35.795 --> 01:24:36.915
And that being said, I

NOTE Confidence: 0.992328

01:24:36.915 --> 01:24:38.515
think the initial months were

NOTE Confidence: 0.992328

01:24:38.515 --> 01:24:40.295
definitely very hard because

NOTE Confidence: 0.92669153

01:24:40.675 --> 01:24:42.215
I couldn't eat and,

NOTE Confidence: 0.9784475

01:24:42.594 --> 01:24:43.715
you know, I had dumping

NOTE Confidence: 0.9784475

01:24:43.715 --> 01:24:45.074
syndrome, and it was very

NOTE Confidence: 0.9784475

01:24:45.074 --> 01:24:45.574
hard.

NOTE Confidence: 0.9992325

01:24:45.875 --> 01:24:47.210
But right now,

NOTE Confidence: 0.9778263

01:24:48.150 --> 01:24:49.430
like, years down the line,

NOTE Confidence: 0.9778263

01:24:49.430 --> 01:24:50.410
I'm able to

NOTE Confidence: 0.90382373

01:24:50.870 --> 01:24:52.489
have a full meal and

NOTE Confidence: 0.90226316

01:24:52.790 --> 01:24:53.770
I'm much better.

NOTE Confidence: 0.9960389

01:24:54.150 --> 01:24:55.670
And just the fact that

NOTE Confidence: 0.9960389

01:24:55.670 --> 01:24:57.290
my parents and my family,

NOTE Confidence: 0.99771464

01:24:58.405 --> 01:24:59.685
we're all kind of, you

NOTE Confidence: 0.99771464

01:24:59.685 --> 01:25:01.525
know, happy that the main

NOTE Confidence: 0.99771464

01:25:01.525 --> 01:25:02.025
source

NOTE Confidence: 0.9834868

01:25:02.405 --> 01:25:03.845
of where the lesion was

NOTE Confidence: 0.9834868

01:25:03.845 --> 01:25:05.225
is gone from my body.

NOTE Confidence: 0.9983615

01:25:05.604 --> 01:25:06.725
So I think that's one

NOTE Confidence: 0.9983615

01:25:06.725 --> 01:25:07.705
sense of, like,

NOTE Confidence: 0.9700817

01:25:08.165 --> 01:25:09.365
relief that me and my

NOTE Confidence: 0.9700817

01:25:09.365 --> 01:25:10.425
family have.

NOTE Confidence: 0.96065885

01:25:10.890 --> 01:25:12.409
And my follow-up PET scans

NOTE Confidence: 0.96065885

01:25:12.409 --> 01:25:14.090
have also come out all

NOTE Confidence: 0.96065885

01:25:14.090 --> 01:25:14.590
clean.

NOTE Confidence: 0.98735154

01:25:15.210 --> 01:25:16.650
So I guess that also

NOTE Confidence: 0.98735154

01:25:16.650 --> 01:25:18.409
kind of helped me and

NOTE Confidence: 0.98735154

01:25:18.409 --> 01:25:19.870
my family make that judgment

NOTE Confidence: 0.9987877

01:25:20.489 --> 01:25:20.989
about

NOTE Confidence: 0.870597

01:25:21.370 --> 01:25:22.810
to go or not with

NOTE Confidence: 0.870597

01:25:22.810 --> 01:25:23.469
the suffragectomy.

NOTE Confidence: 0.97846615

01:25:23.850 --> 01:25:25.290
So, yeah, I think that

NOTE Confidence: 0.97846615

01:25:25.290 --> 01:25:26.110
really helped.

NOTE Confidence: 0.9510446

01:25:27.225 --> 01:25:28.824
Thanks, Deepika. This is really

NOTE Confidence: 0.9510446

01:25:28.824 --> 01:25:30.185
nice to hear your journey

NOTE Confidence: 0.9510446

01:25:30.185 --> 01:25:31.385
and, glad to hear that

NOTE Confidence: 0.9510446

01:25:31.385 --> 01:25:32.125
you recovered.

NOTE Confidence: 0.9581813

01:25:33.304 --> 01:25:34.585
I think part of the

NOTE Confidence: 0.9581813

01:25:34.585 --> 01:25:36.025
decision to do to operate

NOTE Confidence: 0.9581813

01:25:36.025 --> 01:25:37.225
would have also been that

NOTE Confidence: 0.9581813

01:25:37.225 --> 01:25:38.344
you were diagnosed at a

NOTE Confidence: 0.9581813

01:25:38.344 --> 01:25:39.145
very young age, and I

NOTE Confidence: 0.9581813

01:25:39.145 --> 01:25:40.364
think most people

NOTE Confidence: 0.93285435

01:25:41.040 --> 01:25:42.400
to to Gibson's point, most

NOTE Confidence: 0.93285435

01:25:42.400 --> 01:25:43.860
people wouldn't want to risk

NOTE Confidence: 0.93285435

01:25:44.000 --> 01:25:45.520
leaving any tumor behind. So

NOTE Confidence: 0.93285435

01:25:45.520 --> 01:25:46.260
that's great.

NOTE Confidence: 0.9608191

01:25:46.800 --> 01:25:47.520
I have a couple of

NOTE Confidence: 0.9608191

01:25:47.520 --> 01:25:48.560
questions on the chat. I

NOTE Confidence: 0.9608191

01:25:48.560 --> 01:25:50.000
think both I'll try and

NOTE Confidence: 0.9608191

01:25:50.000 --> 01:25:50.500
address.

NOTE Confidence: 0.9850043

01:25:50.960 --> 01:25:52.400
So one question is the

NOTE Confidence: 0.9850043

01:25:52.400 --> 01:25:53.805
question of looking at the

NOTE Confidence: 0.9850043

01:25:53.805 --> 01:25:54.545
addition of trastuzumab

NOTE Confidence: 0.929893

01:25:55.085 --> 01:25:56.864
with FLOT for HER2 positive,

NOTE Confidence: 0.99709845

01:25:57.564 --> 01:25:58.064
adenocarcinoma.

NOTE Confidence: 0.9698562

01:25:58.925 --> 01:26:00.045
So we actually have the

NOTE Confidence: 0.9698562

01:26:00.045 --> 01:26:01.645
innovation trial that looked at

NOTE Confidence: 0.9698562

01:26:01.645 --> 01:26:02.145
this,

NOTE Confidence: 0.9146043

01:26:03.245 --> 01:26:04.844
with both trastuzumab as well

NOTE Confidence: 0.9146043

01:26:04.844 --> 01:26:06.364
as pertuzumab, not with FLOT,

NOTE Confidence: 0.9146043

01:26:06.364 --> 01:26:08.205
but with older chemotherapy regimens,

NOTE Confidence: 0.9146043

01:26:08.205 --> 01:26:09.185
which was negative.

NOTE Confidence: 0.953915

01:26:09.860 --> 01:26:11.079
And so that study,

NOTE Confidence: 0.96535856

01:26:12.500 --> 01:26:14.020
didn't show any benefit in

NOTE Confidence: 0.96535856

01:26:14.020 --> 01:26:15.219
the addition of HER2 in

NOTE Confidence: 0.96535856

01:26:15.219 --> 01:26:17.079
the perioperative setting. And so

NOTE Confidence: 0.96535856

01:26:17.219 --> 01:26:18.739
we need to be careful

NOTE Confidence: 0.96535856

01:26:18.739 --> 01:26:20.340
about extrapolating data from the

NOTE Confidence: 0.96535856

01:26:20.340 --> 01:26:21.780
metastatic setting and moving it

NOTE Confidence: 0.96535856

01:26:21.780 --> 01:26:23.814
into the perioperative setting without

NOTE Confidence: 0.96535856

01:26:23.814 --> 01:26:25.575
having clinical trials support some

NOTE Confidence: 0.96535856

01:26:25.575 --> 01:26:26.395
of these data?

NOTE Confidence: 0.93928087

01:26:26.854 --> 01:26:28.215
The other question was any

NOTE Confidence: 0.93928087

01:26:28.215 --> 01:26:29.835
chance of improving on CROS?

NOTE Confidence: 0.9422726

01:26:30.935 --> 01:26:32.215
That part actually, the truth

NOTE Confidence: 0.9422726

01:26:32.215 --> 01:26:33.575
is, at least at Yale,

NOTE Confidence: 0.9422726

01:26:33.575 --> 01:26:34.935
we all firmly believe that

NOTE Confidence: 0.9422726

01:26:34.935 --> 01:26:36.295
CROS was not the best

NOTE Confidence: 0.9422726

01:26:36.295 --> 01:26:37.995
regimen from a chemo radiation

NOTE Confidence: 0.9422726

01:26:38.055 --> 01:26:38.555
perspective

NOTE Confidence: 0.7326939

01:26:38.935 --> 01:26:39.970
for adenocarcinomas,

NOTE Confidence: 0.89777315

01:26:41.229 --> 01:26:41.729
specifically

NOTE Confidence: 0.9053665

01:26:42.110 --> 01:26:43.710
for squamous cell cancers is

NOTE Confidence: 0.9053665

01:26:43.710 --> 01:26:44.670
a different story, and we

NOTE Confidence: 0.9053665

01:26:44.670 --> 01:26:46.590
think carboxyl in combination with

NOTE Confidence: 0.9053665

01:26:46.590 --> 01:26:48.210
radiation is beneficial.

NOTE Confidence: 0.94337076

01:26:50.430 --> 01:26:52.284
Importantly, the CROS regimen has

NOTE Confidence: 0.94337076

01:26:52.284 --> 01:26:53.324
a much lower dose of

NOTE Confidence: 0.94337076

01:26:53.324 --> 01:26:54.684
radiation with just forty one

NOTE Confidence: 0.94337076

01:26:54.684 --> 01:26:55.965
point four grammes, which is

NOTE Confidence: 0.94337076

01:26:55.965 --> 01:26:57.085
very different from a more

NOTE Confidence: 0.94337076

01:26:57.085 --> 01:26:58.525
definitive dose of radiation, which

NOTE Confidence: 0.94337076

01:26:58.525 --> 01:26:59.905
is fifty point four grammes.

NOTE Confidence: 0.94337076

01:26:59.965 --> 01:27:01.405
And the carbotaxol is at

NOTE Confidence: 0.94337076

01:27:01.405 --> 01:27:02.945
very low doses of chemotherapy,

NOTE Confidence: 0.94337076

01:27:03.164 --> 01:27:05.085
which is, fifty milligrams or

NOTE Confidence: 0.94337076

01:27:05.085 --> 01:27:07.580
kilogram of, paclitaxel weekly for

NOTE Confidence: 0.94337076

01:27:07.580 --> 01:27:09.180
five cycles and one point

NOTE Confidence: 0.94337076

01:27:09.180 --> 01:27:09.660
five,

NOTE Confidence: 0.9157403

01:27:10.700 --> 01:27:11.760
AUC of carboplactin,

NOTE Confidence: 0.96907

01:27:12.300 --> 01:27:13.580
five for five cycles, which

NOTE Confidence: 0.96907

01:27:13.580 --> 01:27:14.939
typically is not good enough

NOTE Confidence: 0.96907

01:27:14.939 --> 01:27:16.780
for systemic control. And so

NOTE Confidence: 0.96907

01:27:16.780 --> 01:27:18.140
most of the regimens that

NOTE Confidence: 0.96907

01:27:18.140 --> 01:27:19.420
we use would have much

NOTE Confidence: 0.96907

01:27:19.420 --> 01:27:20.640
higher doses of chemotherapy,

NOTE Confidence: 0.92602354

01:27:22.395 --> 01:27:24.335
with chemoRAS either using FOLFOX,

NOTE Confidence: 0.92602354

01:27:24.395 --> 01:27:25.595
like the CAOGB eight zero

NOTE Confidence: 0.92602354

01:27:25.595 --> 01:27:27.375
eight zero three regimen, or

NOTE Confidence: 0.92602354

01:27:27.435 --> 01:27:28.715
just having FLOT as a

NOTE Confidence: 0.92602354

01:27:28.715 --> 01:27:29.935
chemotherapy with,

NOTE Confidence: 0.87295943

01:27:30.555 --> 01:27:31.695
five FU oxaliplatin

NOTE Confidence: 0.90115714

01:27:31.995 --> 01:27:32.975
as well as docetaxel,

NOTE Confidence: 0.9630259

01:27:33.755 --> 01:27:35.595
to improve the perioperative outcomes.

NOTE Confidence: 0.9630259

01:27:35.595 --> 01:27:36.600
And this is an area

NOTE Confidence: 0.9630259

01:27:36.600 --> 01:27:37.719
of a lot of controversy

NOTE Confidence: 0.9630259

01:27:37.719 --> 01:27:38.860
and a lot of research,

NOTE Confidence: 0.90584177

01:27:40.679 --> 01:27:42.360
that people are people are

NOTE Confidence: 0.90584177

01:27:42.360 --> 01:27:43.179
working on.

NOTE Confidence: 0.9513092

01:27:43.639 --> 01:27:44.439
We are at the top

NOTE Confidence: 0.9513092

01:27:44.439 --> 01:27:45.159
of the hour, so I'm

NOTE Confidence: 0.9513092

01:27:45.159 --> 01:27:46.199
gonna take a chance take

NOTE Confidence: 0.9513092

01:27:46.199 --> 01:27:47.800
this opportunity to thank everyone

NOTE Confidence: 0.9513092

01:27:47.800 --> 01:27:49.320
for joining us today. Take

NOTE Confidence: 0.9513092

01:27:49.320 --> 01:27:51.344
this opportunity to have, have

NOTE Confidence: 0.9513092

01:27:51.564 --> 01:27:53.405
my fantastic panelists joining me

NOTE Confidence: 0.9513092

01:27:53.405 --> 01:27:54.764
and giving great talks, and,

NOTE Confidence: 0.9837678

01:27:55.804 --> 01:27:56.764
thank you very much for

NOTE Confidence: 0.9837678

01:27:56.764 --> 01:27:57.724
joining us today, and have

NOTE Confidence: 0.9837678

01:27:57.724 --> 01:27:58.465
a great evening.