Center for GI Cancers CME Webinar Series: Biliary Tract Cancer

April 20, 2026

April 16, 2026

Moderated by Jacquelyne Gaddy, MD, MSc, MSCR

Assistant Professor of Medicine (Medical Oncology and Hematology)

Presenters:

Yifei Zhang, MD

Assistant Professor of Medicine (Medical Oncology and Hematology)

Mario Strazzabosco, MD, PhD, MSc

Professor of Medicine, Clinical Program Leader, Liver Cancer Program; Co-Director, Yale Liver Center

Hiroshi Sogawa, MD, MBA

Surgical Director of Liver Transplantation, Transplant & Immunology Surgery

About the speakers

Information

ID: 14079
To Cite: DCA Citation Guide

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00:02Good evening.
00:03Today is April sixteenth,
00:05and welcome to our two
00:06thousand twenty six Center for
00:08GI Cancers CME series.
00:11Tonight, we will focus on
00:13biliary tract cancer specifically.
00:16My name is Jacqueline Gaddy,
00:17and I am an assistant
00:19professor of medicine
00:20and GI medical oncology at
00:22Yale. Thank you so much
00:24for joining us this evening.
00:27I have no disclosures to
00:28review.
00:31I most importantly, besides thanking
00:33all of you for joining
00:34us this evening and those
00:36that may join at a
00:36later date, I also want
00:38to thank my colleagues that
00:39have taken the time to
00:41join us this evening.
00:43Tonight, we will review perioperative
00:46management,
00:47surgical management,
00:48the critical role of hepatology,
00:51and the management of unresectable
00:53and metastatic disease.
00:54I am joined by doctor
00:56Yifei Zhang, a GI medical
00:58oncologist,
00:59doctor Straza Bosco, a hepatologist
01:02and leader of the liver
01:03cancer program and co director
01:05of the Yale Liver Center,
01:08and doctor Sogawa,
01:09the surgical director of liver
01:11transplantation.
01:15I also want to give
01:16a plug for our last
01:17session of the year, which
01:18will be held next month
01:20on May twenty first, which
01:22will be led by doctor
01:23Jill Lacey reviewing pancreatic cancer.
01:30I will get us started
01:31by first providing a simple
01:33background
01:34on biliary tract cancers, which
01:36as I have diagrammed and
01:37pictured here, includes tumor within
01:39the liver and outside of
01:41the liver, which are known
01:42as intrahepatic
01:43and extrahepatic cholangiocarcinoma,
01:45along with gallbladder cancer.
01:48Doctor Straza Bosco will additionally
01:51further discuss the background of
01:52biliary tract cancers, including the
01:54heterogeneity,
01:56mutational profile,
01:58and diagnostic evaluation.
02:03When compared to other GI
02:04tumors, such as colon cancer,
02:06which we often also treat,
02:09Biliary tract cancers are certainly
02:11rare with approximately twelve to
02:13thirteen thousand new cases in
02:14the US per year, with
02:16majority of these being cholangiocarcinoma,
02:18with intrahepatic
02:20specifically
02:21being the most common form
02:22in Western countries.
02:25More specifically, intrahepatic cholangiocarcinoma
02:27has a rising incidence and
02:29mortality.
02:30I have known risk factors
02:32here that are listed, which
02:33again doctor Straza Bosco may
02:35further review. But I think
02:36what it's also really important
02:38to know is that many
02:39patients actually present without any
02:41established risk factor, and they
02:43often, unfortunately, present with advanced
02:46stage disease.
02:51As stated previously, most patients
02:52present with advanced stage disease
02:54with only about twenty five
02:56percent of patients actually presenting
02:58with resectable disease, which doctor
03:00Sobo will review
03:01momentarily.
03:03Despite resection,
03:05up to sixty percent of
03:06patients also recur.
03:08The overall survival rates can
03:10vary by tumor type with
03:12intrahepatic cholangiocarcinoma
03:14having porous prognosis.
03:17Picture here
03:18are
03:19the prognostic
03:20factors that we consider in
03:21biliary tract cancers. And if
03:23you keep these prognostic factors
03:25in mind, these are often
03:26the prognostic factors and the
03:28eligibility criteria that are considered
03:30for high risk clinical trials,
03:32but they include performance status,
03:35resection margins being positive,
03:38lymphometastases,
03:40vascular invasion,
03:42increased
03:43CA ninety nine,
03:44poor histological
03:45differentiation,
03:47along with advanced stage.
03:51As mentioned earlier, my colleagues
03:53and I will discuss
03:54different forms of management depending
03:56on the stage
03:57of biliary tract cancers.
04:00I will now transition to
04:02doctor Straza Bosco, who will
04:04review the role of hepatology
04:05in biliary tract cancer management,
04:08who will then be followed
04:09by doctor Sogawa, who will
04:10discuss the surgical management of
04:12biliary tract cancers.
04:14I encourage each of you
04:15to put any questions in
04:16the chat or enter them
04:18in the question and answer
04:19format. And we will try
04:21to answer them possibly during
04:22the presentation,
04:23but may also save them
04:25for the conclusion of our
04:26session.
04:31Thank you very much,
04:32Jackie, for this beautiful introduction.
04:36Bear with me a second
04:38while I try and fail
04:40to share my
04:42screen? No problem at all,
04:44and I'll let you know
04:45when it's showing.
04:46Okay.
04:50So it should be this
04:51one.
04:53Okay.
04:56Is it showing? It's perfect.
04:58Okay. Thank you very much.
05:00So
05:01my task
05:02tonight is to try to,
05:05refresh,
05:05what
05:06a hepatologist
05:07should know about this, rare,
05:11and yet,
05:13difficult
05:15and prognostically,
05:17unfortunate
05:18cancer.
05:19Okay? And I this is
05:21my disclosure.
05:23So
05:25BERI tract cancer in cholangiocarcinoma
05:28is a heterogeneous
05:29under several,
05:32different categories. So first of
05:34all, is heterogeneous in terms
05:35of cell of origin,
05:37location,
05:39pattern of
05:40growth, morphology,
05:42mutational landscape, and clinical manifestation.
05:44And this cartoon
05:46kind of make the point.
05:48Only recently,
05:49the different tumor have been
05:52classified in a more homogeneous
05:54way.
05:55And so according to the
05:57order of the
05:59the bile ducts, that are
06:01affected by the cancer, we
06:02distinguish the intraepartic
06:04cancer,
06:05cholangiocarcinoma,
06:06the perihealer
06:08cholangiocarcinoma,
06:10and the distal cholangiocarcinoma.
06:12These are,
06:15also,
06:18different histologically
06:20And mutationally,
06:22so, for example,
06:24the.
06:26Intrepatic cholangiocarcinoma
06:28is generated.
06:30From the small interpathic bile
06:32duct and may have different
06:34histological
06:36feature. You see here the
06:38cholangiocellular,
06:40so the smaller,
06:41branches of the bile duct
06:43from the small
06:44type.
06:46And, here you see an
06:47example
06:48of the,
06:49cancer
06:50arising from the large bile
06:52ducts and from the distal
06:54bile duct. But, also, they
06:56are heterogeneous
06:56in terms of type of
06:58growth. So you may have,
07:01the classic
07:02mass forming
07:04cholangiocarcinoma
07:06or the periductal one, but
07:08you may also have the
07:09one that is introductory, and
07:11this is more difficult to
07:12diagnose. Of course.
07:15So
07:16I I briefly mentioned and
07:17also Jack is told that
07:19they are,
07:21their mutational landscape is different
07:23according to their location and
07:25type.
07:26Here, I have,
07:28only show
07:29some of the different,
07:32mutations that are present, but
07:34I want to
07:35draw your attention to the
07:37IDH12,
07:38the
07:39in the.
07:41That can happen in twenty,
07:43twenty two percent of the
07:44intrahepatic,
07:45cholangiocarcinoma
07:48together with other. Whereas in
07:50the periheolar
07:51cholangiocarcinoma,
07:52the b the KRAS,
07:55and have two, three,
07:56and,
07:59TP53 becomes more frequent and
08:01this
08:03is more or less also
08:04the case in the distal,
08:06whereas the IDH12 and the
08:07FTR2
08:09are more classic, really on
08:10the intrepatic
08:12thing. Is this relevant? Yes.
08:14It is. Because,
08:16of the many,
08:18different,
08:20mutations that have been associated
08:21with,
08:23cholangiocarcinoma,
08:25many of them, and they're
08:27just briefly listed here,
08:30can be targeted.
08:33So the first,
08:36the first message here is
08:38that it's always
08:39mandatory, I think,
08:41to,
08:42genotype
08:44this, cancer from from from
08:47the biopsy because it may
08:49have
08:52a treatment.
08:54It may guide the treatment.
08:55Okay?
08:56Now in terms of
09:00risk factor,
09:01as Jackie
09:02said, most cases are sporadic,
09:04so we are not able
09:05to,
09:07find
09:09a cause or a risk
09:11factor. But there are
09:14some condition that are
09:17low that are rare with
09:19low prevalence, like
09:21primary sclerosis, cholangitis,
09:23choroidal disease,
09:25cholestical cyst,
09:27presence of large stones in
09:28the bladder,
09:29and but also chronic liver
09:31disease,
09:32inflammatory, like,
09:34hepatitis,
09:36and HBV,
09:39in which that
09:43that that these condition are
09:44associated with a higher
09:46possibility of of liver cancer.
09:48For example, in the primary
09:49sclerosing cholangitis,
09:51up to fifteen percent of
09:52this patient developed
09:54in the course of their
09:55life, echolangiocarcinoma.
09:58So these are condition that
10:01are not very prevalent,
10:04but they have a significant
10:05risk. So if you look
10:07here into this this plot,
10:10so the risk of,
10:13this is the risk of
10:13having the cancer, and this
10:15is instead the prevalence. So
10:17there are
10:19some condition that have a
10:20high prevalence, but they are
10:22not, but they are rare.
10:23On the other hand, there
10:24are high prevalence factor
10:27that confer a moderate risk.
10:30And we should be aware
10:31of this because
10:33we think to this condition
10:35mostly in terms of
10:37risk factor for hepatocellular
10:39carcinoma,
10:40but that's not the case.
10:42Some of these patient, and
10:43we will see that,
10:45may actually have a cholangiocarcinoma.
10:48Among that, there are alcohol
10:50use disorder, diabetes,
10:53and I will
10:54underlie also the metabolic associated
10:57liver disease,
11:00in his inflammatory
11:01form, which is called MASH.
11:04Some of these patient, particularly
11:06if they are not fully
11:08cirrhotic, may actually have a
11:10intrepartic cholangiocarcinoma.
11:11So this is a very
11:12important second method that you
11:14should bear in mind.
11:16So what happens in,
11:18in primary sclerosing cholangitis?
11:22There is a,
11:24presence of multifocal stricture. In
11:26this multifocal stricture, we harbor
11:29infections,
11:30and chronic infection infection will
11:33end up causing DNA damage,
11:35metaplasia,
11:36low grade dysplasia, high grade,
11:38and cholangiocarcinoma.
11:40And as I said, up
11:41to fifteen percent of the
11:42patient will sooner or later
11:44develop that. So what do
11:45we do in this case?
11:46I mean,
11:49in this case,
11:50we will have it. We'll
11:51discuss that after.
11:53There are surveillance,
11:55protocols. However,
11:57they are not that established
11:59as in the case of
12:00hepatocellular carcinoma.
12:03As I said before, a
12:04condition in which we need
12:06to be very careful
12:07is
12:09steptotic liver disease. In this
12:11case, this is a still
12:12unpublished
12:14series from from Padova,
12:17but it was found that
12:22that in thirty percent of
12:23the cases,
12:25there was a cholangiocarcinoma
12:27in the resected sample rather
12:28than an HCC. And you
12:30can see in this beautiful
12:31slide, the border between the
12:33steatotic,
12:34liver
12:36and and and the cholangiocarcinoma.
12:38So be very careful, and
12:40this is a case that
12:41we had here.
12:43This patient, seventy nine years
12:44old, female,
12:46known to have
12:47a metabolic associated
12:49liver disease related cirrhosis,
12:52overweight with diabetes, high blood
12:54pressure. So all the classic,
12:59science of a potential,
13:02mass holder
13:03shows in the clinic with
13:07with the liver lesion
13:09that might have been classified
13:11as l r five, but
13:13not everything was
13:15consistent with l r five.
13:19And in particular, you see
13:20this this incision here,
13:23this capsule retraction, which were
13:25very suspicious
13:27at the time.
13:28So we decided to do
13:29a biopsy. And and in
13:31fact,
13:32you can see the background
13:33liver, which is classic for
13:37a metabolic associated,
13:39cirrhosis.
13:40And here, the the tumor
13:42was a cholangiocarcinoma.
13:44This patient,
13:46underwent surgery.
13:49Sorry. And,
13:50she's actually doing fine,
13:52four years after,
13:55after the treatment.
13:56So, again,
13:59we need to be very,
14:00cognizant that a lesion in
14:02a, steatotic liver may actually
14:04be
14:05a cholangiocarcinoma.
14:07Okay.
14:08This is a series,
14:09of
14:11more than two thousand patient,
14:13followed by a European registry.
14:17And
14:17you see there,
14:19these are divided in intrahepatic,
14:23perihealer,
14:24and distal.
14:26The risk factor associated
14:28again are in the case
14:30of intrahepatic,
14:31obesity,
14:32diabetes,
14:34viral hepatitis, and cirrhosis.
14:38In the case of the,
14:40perihela
14:42cholangiocarcinoma,
14:43the main factor is actually
14:44the PSC.
14:47Whereas in in the case
14:48of the distal, we have
14:50a metabolic condition like hyperthritillary
14:52terendemia
14:53and and, gastron disease.
14:57So this again confirmed
14:59that the
15:00risk factor
15:02are similar
15:04to those of the hepatocellular
15:05carcinoma somehow.
15:07So how do we go
15:08about the diagnosis? Of course,
15:10we the MRI
15:12is our,
15:14principal
15:15instrument
15:16and the MRCP that is
15:18always,
15:19to be done,
15:21even before
15:24the
15:26ERCP.
15:28Actually, the ERCP now is
15:29is never,
15:31indicated,
15:32if you don't do an
15:33MRCP before.
15:35But the MRCP,
15:36you can do,
15:38either biopsies and lesion that
15:40that that you can see
15:42with a spyglass
15:43or,
15:44do a brush.
15:46We'll talk more about the
15:48brushing. If you see something,
15:50that is suspect, you can
15:52use a endoscopic
15:53ultrasound.
15:55And,
15:57hopefully,
15:58soon,
15:59we will also be able
16:01to use liquid biopsy in
16:03terms of,
16:06ctDNA.
16:15So this is you usually,
16:18the the diagnosis in the
16:20PSC
16:21was done by
16:22brushing. Brushing can give you
16:23a cytological reading. Brushwing can
16:26give you a,
16:29more genetically determined
16:31fish, for example, for certain,
16:37expression of,
16:39genomic expression, but this is
16:41never really,
16:43very,
16:44sensitive. For example, see the
16:46fish is only fifty,
16:48fifty five percent,
16:50of of positivity. So now
16:52there is this new,
16:54technology, which is called Billy
16:56Sack on brushing.
16:57It looks for a certain
16:59sector of a potential mutation
17:01that are most frequent in
17:04in cholangiocarcinoma.
17:06And,
17:07here you can see that,
17:10they
17:11this approach is able to
17:12find a mutation
17:14in patient that would be
17:16otherwise considered negative.
17:18So
17:19the combination
17:20of,
17:23PSYTOLOGY
17:24during the brushing
17:26can,
17:26bring our diagnostic
17:30precision and and sensitivity
17:32up to eighty five percent.
17:34So that is the the
17:35the future in the follow-up
17:36of these patients.
17:39So,
17:40the good thing is that
17:42also the treatment,
17:46prospect are increasing.
17:48Doctor Sugawa will talk about
17:50the resection and the transplant,
17:52and, I think our medical
17:54oncology,
17:56colleague will talk about chemotherapy
17:59and, immunotherapy.
18:01There are more and more,
18:03example of the use of
18:05local regional treatment
18:06for for the treatment of
18:08intraepartic angiocarcinoma.
18:10They can be ablation or
18:12y ninety preferentially.
18:15Stereotactic
18:15body radiation therapy is also
18:17is also
18:19a good alternative for patients
18:21that are otherwise unable to
18:23be treated differently.
18:25I think that as Milo,
18:27we also have a protocol
18:28of
18:29of a particular infusion.
18:31And,
18:32if nothing else work,
18:35you can put a positive
18:37standing.
18:40A little,
18:42intro to what doctor Sugawa
18:44would say,
18:45and, from the US National
18:48Cancer Database
18:49comes for his retrospective
18:51study that shows that,
18:54transplant for early stage intrahepatic
18:57cholangiocarcinoma
18:58is actually actually has a
19:00very good
19:02very good
19:03survival
19:04as respect to other
19:06approaches.
19:07And now the
19:09UNOS also has set up
19:11certain criteria
19:13so that you can actually
19:14transfer this patient.
19:16So,
19:17just to end
19:20and to summarize, so, chronic
19:23carcinoma is a diverse group
19:25of cancer. It's with specific
19:27clinical manifestation.
19:29It's more frequent in a
19:31condition in which there is
19:32chronic
19:33inflammation in the liver.
19:35Their
19:36main characteristic
19:37histologically
19:38is to have a stronger,
19:39there's more plastic
19:41reaction. So the tumor reactive
19:42stroma is very important and
19:44is
19:46believed to be,
19:48one of the condition that
19:49facilitates the metastasis.
19:52They are, in fact,
19:54very
19:55high invasiveness.
19:57And in several cases, unfortunately,
19:59by the time you do
20:00the diagnosis, there is already
20:02a lymph node metastaticization.
20:05The epidemiology
20:06is changing because
20:07of the actual,
20:10very high prevalence of, steatotic
20:13liver disease.
20:14And,
20:15surgery is potentially correlative,
20:18but, can be offered usually
20:20to less than twenty five
20:21percent of the cases. But
20:22we do have
20:24liver transplantation,
20:26And I stop here because
20:28I don't want to enter
20:29the domain of my colleagues.
20:32So finally, this is the,
20:34telephone number of entry of
20:36the Yale liver cancer. And
20:37if I can draw the
20:39attention, whoever is interested,
20:42the FASB,
20:43will have, in August in
20:45Washington,
20:48meeting on the biocomplexity
20:50and molecular medicine liver cancer.
20:53And with that, I unshare.
20:55Thank you. Thank you so
20:57much, doctor Strazzavasco.
20:58That was a great
21:00presentation and overview of how
21:02to approach cholangiocarcinoma
21:04and other biliary tract cancers
21:06in the space of hepatology,
21:08and you also did an
21:09amazing job of transitioning
21:11it over to doctor Sogawa.
21:13So doctor Sogawa will now
21:14spend some time discussing transplant
21:17and resection options for patients
21:19with biliary tract cancers.
21:21Awesome. Thank you.
21:24Let's see. I can share.
21:27Are you able to see?
21:29That's perfect.
21:32Okay.
21:36Just one second.
21:49Okay. So,
21:50good evening, everyone.
21:51Thank,
21:53thank you for,
21:56invitation, and, I'm happy to
21:58talk about surgical management over
21:59chorangiocarcinoma
22:01resection and antibody transplantation.
22:09So it's already, doctor Strauss
22:11Vasco showed us that stem
22:13diagram.
22:14This is very important. In
22:16terms of surgical treatment,
22:18the location dictate what kind
22:19of treatment,
22:21is appropriate.
22:23So the,
22:24intracellular,
22:25intrahepatic cholangiocarcinoma,
22:27which is ten to twenty
22:28percent,
22:29essentially, you wanna do resection,
22:32prostaglandin
22:32lymph node dissection,
22:34or very selective case, the
22:36difference for transplantation is a
22:37indication.
22:38Indicated.
22:39Are you advancing your slides?
22:41We still see the title
22:42slide.
22:43Oh,
22:46okay.
22:59K. Sorry. I am advancing,
23:02from end, but seems like
23:04it's not the case.
23:05Just one second, please. Let
23:07me just stop share. No
23:09problem.
23:18Let me try again.
23:32Okay.
23:33I guess okay. Alright. So
23:35let me let me try
23:36a little
23:42so, again, so I was
23:43talking about the location of
23:44a chorangial carcinoma
23:46dictate
23:47what kind of surgical treatment
23:49is necessary.
23:51Intercepter
23:52interhepatic
23:53chorangial carcinoma,
23:54usually liver resection plus minus
23:57the inflamydinectomy.
23:59Some case, liver transplantation is
24:01indicated.
24:03And if it's a perihilar
24:05chorangial carcinoma, which is people
24:07call Krebskin tumor,
24:09which is required frequently
24:11right hepatectomy, left hepatectomy,
24:13sometimes,
24:14right price segmentectomy
24:16or left right segmentectomy.
24:17Usually, you need a coded
24:19role resection.
24:21Some of the cracked skin
24:22tumor,
24:25the the particularly Mayo Mayo
24:26protocol, liver transplantation,
24:28has a good outcome.
24:31And when you have a
24:32distal cholangiocarcinoma,
24:35the the the the
24:37that cholangiocarcinoma,
24:38is a little bit better
24:41outcome generally speaking, but it's
24:43a distal,
24:45cholangiocarcinoma.
24:46The treatment option,
24:47treatment choice is a Whipple,
24:50pancreaticulodenectomy.
24:59Do you see a distal
25:00chorangial?
25:01Yes. We do. You still.
25:02Yeah.
25:03So the I'm just briefly
25:05talking about the distal chorangial.
25:08As I mentioned in prior
25:09slide, it's, Whipple.
25:11So the workup and also
25:13treatment
25:14is is similar to Whipple's
25:16procedure.
25:18Outcome is still even r
25:20zero resection.
25:21It's better than the pancreas
25:22cancer, generally speaking, by twenty
25:24five to thirty percent.
25:26It's important to have,
25:29r zero resection, if it's
25:30possible.
25:31And then portal vein recon
25:34reconstruction
25:35and lymph node dissection,
25:36these are,
25:37also doesn't change outcomes.
25:45So let me talk about
25:46the surgical,
25:48liver,
25:49resection option for cracked skin
25:51tumor.
25:52Cracked skin tumor is classified
25:54is a biz it is
25:55called bismuth classification.
25:58When you see, type one,
26:00it's mainly,
26:01common hepatic duct and the
26:03type two including hilum.
26:06And type three a, three
26:08three b is is on
26:10the right side or left
26:12side.
26:13And,
26:14bismuth four including both right
26:17and left hepatic duct. So
26:19what does that means, from
26:21the surgical standpoint? And type
26:23one and type two,
26:25generally speaking, you wanna take
26:26a you know, remove,
26:28excise the bile duct
26:30and then plus minus if
26:31you need to have a
26:32hepatic artery and the motor
26:34vein.
26:34You need to have a,
26:36resection if it's needed. But
26:39generally speaking, you need to
26:40have a reconstruction and who
26:41and why.
26:43But relatively,
26:45you don't need to have
26:46a liver resection, not necessarily.
26:48However, type three a or
26:50three b
26:51require major liver resection.
26:54And,
26:55and also the same way
26:57hepatocar three portal vein,
26:59involvement, you need to have
27:00a reconstruction.
27:03That's that's a bigger operation,
27:05generally speaking. And also, you
27:07need to have reconstruction
27:08of bile duct.
27:10Now bismuth four is more
27:12troublesome
27:13because you you have some
27:15both of the hepatic duct
27:16right and left are involved.
27:18So what is that means?
27:19You do need to have
27:21right trisegmentectomy.
27:23So if you have this
27:24only left lateral segment, twenty
27:26percent is left over, which
27:28is generally it's it's too
27:30small
27:31as a remnant. You would
27:32like to have a thirty
27:33to forty percent. So,
27:35in that case, you do
27:36need to have a portal
27:38portal vein embolization
27:39to make a left lateral
27:41segment bigger.
27:43And then, if it's the
27:45other side, it's you might
27:46need to have a left
27:47trisemantectomy.
27:49So these are,
27:51surgery,
27:52outcome, particularly,
27:56like in Nagoya's group, they
27:57have
27:58extraordinary
27:59outcomes.
28:00But
28:01the aim is try to
28:02get r zero resection. It's
28:04r you know, compared to
28:06r one resection,
28:07outcome is, is a is
28:09a different overall five year
28:10survival, thirty to forty percent
28:12if you have r zero
28:14resection. Resection, but r one's
28:15microscopic
28:16is leftover,
28:18is only ten percent.
28:24Preoperative
28:25and adjuvant,
28:27consideration,
28:29is I've already kinda mentioned,
28:33portal vein embolization
28:35to increase,
28:37remnant of liver.
28:39That's a key. And, you
28:41used to be a PTBD,
28:43drainage of a bile duct.
28:45When you have obstructing,
28:47it doesn't function.
28:49But we prefer,
28:51ERCP
28:52to decompress
28:53bile duct,
28:55in terms of a tumor
28:56outcomes. And then, I'm done
28:58going for Azovant and systemic
29:00treatment, but these are,
29:03very important, in the preoperative
29:06treatment of surgical treat, surgical
29:08therapy.
29:11And so there's two landmark
29:13studies. One is from Sloan
29:15Kettering, and one is from
29:17Nagano's group.
29:19Nagino,
29:20and numerous, they have tremendous
29:22outcomes.
29:24But, overall,
29:25the,
29:25when you have a good
29:27liver resection,
29:28you could achieve,
29:30thirty to fifty percent of,
29:33survivals,
29:35but these are selected cases.
29:39Now I just wanna mention
29:40about cracked skin tumor,
29:42Mayo protocol.
29:44Mayo group has been,
29:46advocating for liver transplantation
29:48for this cracked skin tumor.
29:51They are very, very,
29:54extensive protocol,
29:56prior to transplant and also
29:58before, when you're listing a
30:00patient.
30:02Then,
30:04it's it's by all means,
30:05it's very selected
30:07cases. The original study was
30:09from PSC.
30:11And then when you have
30:12the, cholangiocarcinoma,
30:13they find out. They're going
30:15for transplant. But even that,
30:17the de novo, without the
30:18PSC,
30:20they apply the same methodology,
30:22and it seems like it's
30:23achieving the same outcomes.
30:25However, because of,
30:27lots of,
30:29this is truly multi multidisciplinary
30:32preparations
30:33needed. Not too many transplant
30:35centers, not necessarily be support
30:37that treatment. However,
30:41the outcomes,
30:43are
30:45very good outcomes. Five years
30:47fibro is about sixty five
30:49percent,
30:50both PSC and non PSC.
30:53The UNOS actually,
30:55will give, exception point if
30:57it's a meet criteria for
30:59this Kratzkin tumor liver transplant
31:01case.
31:04The original studies, is a
31:07Mayo studies.
31:08That was confirmed by,
31:11worldwide,
31:12unit studies and also international,
31:16studies
31:17as well.
31:21Now,
31:22I think this is more
31:23focusing on for intracellular
31:26intrahepatic,
31:27cholangiocarcinoma.
31:30The reason why being,
31:32it seems like incidence of
31:34intrahepatic
31:35cholangiocarcinoma
31:36has increasing,
31:38as well as,
31:40trans liver transplantation
31:42for intrahepatic
31:43liver,
31:44cholangiocarcinoma
31:46has progressed tremendously.
31:49But overall, the PRINCEPRO is,
31:52something,
31:53similar.
31:55However, resection,
31:57is almost like a hepacillary
31:59carcinoma liver resection.
32:01Maybe only difference would be,
32:04would be ideal to obtain,
32:07lymph node dissection,
32:09to have a more, lymph
32:10node is that will be
32:11a prognostic and also therapeutic.
32:15However,
32:16five year,
32:18survival,
32:19r zero resection steroids twenty
32:21five to thirty five percent,
32:23of, interest,
32:25intrahepatic cholangiocarcinoma.
32:31And landmark studies is,
32:33Hopkins and,
32:35Sloan's group.
32:38Its outcome is something similar.
32:40Generally speaking,
32:41it's the importance
32:43of r zero section,
32:45for surgical cases.
32:48And the challenge is sometimes
32:49is, do you have,
32:51enough remnant volume
32:53after resection? That's that's a
32:55challenge in cases, particularly cirrhotic
32:57patient.
33:02So now,
33:04maybe last, particularly,
33:07last five years or so,
33:10the this, you know, transplant
33:12community,
33:12we are more focusing on
33:14it is called transplant on
33:16colosy.
33:17So the hepatocellular carcinoma, obviously,
33:20we've been transplanting for many,
33:22many years.
33:23However,
33:24we we start focusing on
33:26for cholangiocarcinoma
33:28and also colorectal metastasis
33:30to the liver. Some selected
33:32cases is. And,
33:35particularly opening up idea
33:37of, and also people pay
33:39attention to,
33:41this, chorangiocarcinoma
33:43liver transplantation
33:44is,
33:45in two thousand fourteen, sixteen,
33:49Spanish studies and, which shows
33:51about, below two centimeter,
33:54chorangiocarcinoma.
33:55And the transplant outcome is
33:57essentially fantastic,
33:59almost,
34:00a hundred percent, survival,
34:02for very,
34:04small number of cases.
34:07And that's also confirmed in
34:09multiple studies.
34:10And,
34:12as doctor Suresh Vasco had
34:14showed, actually,
34:16you know, three centimeter cut
34:18off. It depends on, studies,
34:20but that was,
34:23made into
34:25UNOS,
34:26create a policy for UNOS
34:28exception.
34:30It's smaller than three centimeter
34:31of cholangiocarcinoma
34:33with six months,
34:35observation.
34:36As far as this doesn't
34:37progress,
34:39UNOS will give,
34:41it is called MMT minus
34:43three, which is like a
34:44MER score twenty eight, the
34:46same as a hepatocellular carcinoma
34:48when you have exception point.
34:50So that will open up,
34:52the big paradigm
34:54for,
34:55liver transplantation for intrahepatic
34:58liver,
34:59cholangiocarcinoma.
35:03So the,
35:04so rational array is still
35:07even,
35:08r zero resection case.
35:10Liver resection does not give
35:12you,
35:14great outcome.
35:16And then the small
35:18size
35:19or
35:20intrahepatic
35:21liver
35:22chorangiocarcinoma
35:23outcome
35:24seems to be promising.
35:28Therefore,
35:29and ours and the unit's,
35:31change of policy. So the
35:32last year,
35:34I asked,
35:36doctor Jaffe,
35:37you know, our hepatologist, and
35:39then working with all the
35:40SMILOs,
35:42group,
35:43we create,
35:44Yale's,
35:45chorangiocarcinoma
35:46protocol,
35:47for liver transplantation. I would
35:49like to show it to
35:50you.
35:53So the inclusion this is
35:55the inclusion criteria and exclusion
35:57criteria.
35:58Inclusion criteria is, is adult
36:00and, either,
36:03cholangiocarcinoma,
36:04by tissue diagnosis
36:06or mixed tumor, cholangiocarcinoma,
36:10that can be included.
36:13And, obviously,
36:14there's no
36:15lymph node or some distance
36:17of metathesis,
36:19that would be excluded,
36:20from the criteria.
36:25And and, obviously, there's,
36:28patient need to tolerate the
36:30transplant, so the,
36:32cardiopulmonary
36:34function need to be appropriate.
36:38Workup and staging is, something
36:41similar to,
36:44as
36:44a,
36:46workup for, cholangiocarcinoma,
36:48MRI, CT scan,
36:50and then also PET scan.
36:54And we do need to
36:55have tissue diagnosis.
37:00So this is a major,
37:01probably,
37:02takeaway from,
37:04our protocol.
37:06So we don't,
37:09exclude,
37:10the size. If we let's
37:12say, even, like, ten centimeter
37:13cholangiocarcinoma,
37:15that's not necessarily the automatic,
37:17no for,
37:19that protocol.
37:22It's more important would be
37:23a tumor biology,
37:25has a response to neoadjuvant
37:27treatment.
37:28But we do we cut
37:30we make a cut with
37:31two centimeter versus above two
37:33centimeter. Below the two centimeter,
37:36the patient will go, like,
37:37hypocerebral carcinoma,
37:39going to have a neoadsibone
37:41treatment such as particularly for
37:43this is, like, Y ninety
37:45or,
37:46radiation based, that'd be better.
37:47But, abrasion,
37:50try to maintain,
37:51for the next six months.
37:54Then,
37:57the, patient may,
37:59have a MET score. So
38:01the transplantation,
38:03from deceased donor is a
38:04feasible option.
38:06Now if above two centimeter
38:08or mars multifocal,
38:12cholangiocarcinoma
38:14And then, we mandated,
38:17neosporin the chemo treatment, essentially,
38:20and then to see the
38:21response.
38:23The issue is,
38:26above three centimeter,
38:29the UNOS does not give
38:31you exception point. So so
38:33that means if you have
38:35a multiple multifocal,
38:38cholangiocarcinoma
38:39or,
38:40if,
38:42above,
38:44above three centimeter
38:45tumor,
38:46then,
38:47the only option will be
38:49a living donor liver transplant.
38:51So that's the only,
38:52the problem is. But,
38:54none of this,
38:57We will be able to
38:59see the tumor biology. So
39:01if it's have a response
39:02to it, even to, like,
39:03say, ten centimeter chorangiocarcinoma,
39:07if you, if the patient
39:09have a good tumor response,
39:11to a chemo,
39:13as far as the living
39:14donor is available, then, we
39:16we will,
39:17after we discuss in,
39:21tumor board and also, the
39:22meeting,
39:23we will,
39:25trying to go for live
39:27donor liver transplant.
39:32So, again, this is something
39:34it's it's the same,
39:36same same,
39:37same in a different,
39:40color, but,
39:41so two centimeter and above
39:43two centimeter. This is a
39:44year year's protocol.
39:47Each institution have a different
39:49protocol, but,
39:51we are open to,
39:53have this, patient,
39:56coming to this protocol. We
39:58we just,
39:59kind of finalized
40:01few months ago.
40:04And,
40:06it's important to have a
40:08postoperative,
40:10tree surveillance.
40:12So,
40:14MRI,
40:15over abdomen and also the
40:17CT scan of chest. That's
40:19every three months, every six
40:20months,
40:22and then,
40:24so creating tumor DNA,
40:26and then we will,
40:28do a surveillance like a
40:29hepatocellular carcinoma post reverse transplantation.
40:37I think because we missed
40:39one one side maybe.
40:42Oh, here.
40:44After the transplant, email suppression,
40:47user reusing attack or emails
40:49in the beginning,
40:51but at least from a
40:52certain point or earlier or
40:55some selected case even from
40:56the beginning,
40:57we were using,
40:58rapamycin.
41:00That's,
41:02that'd be a potential benefit,
41:04for antitumor effect,
41:07and then corticosteroid
41:08for three months.
41:13And back to in terms
41:15of surgery,
41:15there's some,
41:17things,
41:18it's important. We
41:21actually, generally speaking, it's a,
41:22you know, liver transplant program
41:24we're using in machine perfusion.
41:27So once the liver is
41:28out, from deceased donor, we
41:30put into the
41:31normal thermic machine perfusion.
41:33You know, normal, oxygenated blood
41:36is coming in. So you
41:37don't have to,
41:39rushing into the transplant within
41:41eight hours or twelve hours.
41:43We can wait. So what
41:45does that means is
41:46this case, hepatectomy,
41:49maybe,
41:50a little bit tricky because
41:51of radiation, chemotherapy.
41:55So but we we can
41:57take a time to do
41:58a hepatectomy
41:59about removing the liver and
42:01put the livers in.
42:03And particularly
42:05radiation, we have to be
42:06careful about, tilia and the
42:08biliary reconstructions.
42:10And living donor is certainly,
42:12could be a,
42:14very important,
42:15role, particularly for the patient,
42:17above three centimeter,
42:19chorangio or multiple chorangiocarcinoma.
42:22As far as they have
42:23good response to chemotherapy,
42:27these are,
42:28good candidates for liver transplantation.
42:34So my key, key takeaway
42:36is,
42:38always r zero resection is,
42:40most important from surgical standpoint.
42:44Anatomy
42:44where the location is,
42:46that dictates surgical treatment.
42:50Liver transplant
42:51patient,
42:52outcome seems like transformative
42:54for selected,
42:56CT scan tumor or intrahepatic,
42:59craniocarcinoma.
43:02Multidisciplinary
43:03management is essential,
43:05and,
43:07obviously,
43:08hepatologist and medical oncologist, radiation
43:11oncologist,
43:12intervention radiologist.
43:14And,
43:15so,
43:16you know, it's a cancer
43:17treatment is generally speaking,
43:20we do this, but particularly
43:22so for chorangiocarcinoma,
43:25in very,
43:26surgical treatment.
43:29And then,
43:30emerging therapies,
43:31changing the landscape including a
43:33transplant, but immunotherapies,
43:36I I think that's be
43:37a
43:38good,
43:39transition to next speaker, I
43:41believe.
43:43Doctor Sogoa, that was amazing.
43:45Thank you so much. It
43:46really shows that
43:47so much has changed and
43:49evolved in the space of
43:50managing cholangiocarcinoma
43:52and allowing for more hope
43:53and better options for our
43:55patients. So thank you so
43:56much. I will
43:58now begin to discuss
44:00systemic therapy in the perioperative
44:02setting. If you wanna just
44:04stop sharing screen, and I
44:05will hopefully
44:07be able to do the
44:07same.
44:09Yep.
44:10Thank you. Thank you.
44:21I think as you said,
44:22that was a great
44:24transition to discussing systemic therapy.
44:27When we think about all
44:28that doctor Sogawa, doctor Straza
44:30Bosco has shared this evening
44:31so far, I think that
44:33it's now a good time
44:34to discuss, well, what do
44:35we do in the perioperative
44:37setting? So I will spend
44:39some time discussing
44:40options for patients in the
44:42neoadjuvant setting.
44:44I will review a couple
44:45of studies, but also keep
44:47our time, in mind as
44:48well. But I'll also discuss
44:50adjuvant therapy as doctor Sogawa
44:52very briefly alluded to.
44:54I will discuss hepatic arterial
44:56infusion therapy, but save a
44:58little bit of time for
44:59my colleague, doctor Zeng, to
45:00discuss that as well briefly.
45:02And then we will end
45:03with discussing
45:05metastatic and unresectable
45:07management.
45:09For biliary tract cancers, there's
45:12evidence that the use of
45:13chemotherapy is appropriate in nearly
45:15all settings,
45:17especially,
45:18in the adjuvant setting, but
45:19most importantly,
45:21as doctor Zhang will discuss,
45:22in the metastatic setting.
45:24But there has been recent
45:26data that further supports what
45:28are options that we can
45:29consider in the neoadjuvant
45:32setting.
45:33I'm going to spend some
45:34time first discussing what our
45:35options are currently that are
45:37evolving in the neoadjuvant setting.
45:40And that particularly,
45:42as I have listed here,
45:43is the ZsaB NEOGOLD study,
45:45which was just published,
45:46I think, maybe less than
45:48a couple months ago but
45:49earlier this year.
45:51And there is an open
45:52clinical trial, which I will
45:53discuss,
45:55also the BILCAP study,
45:57and then, as I said,
45:58HAI therapy.
46:04I now will briefly discuss
46:06the neoadjuvant gulp study.
46:09The neoadjuvant gulp study was
46:11recently published, and what that
46:13study looked at ultimately
46:14was the role of neoadjuvant
46:16chemotherapy
46:18plus immunotherapy
46:19plus targeted therapy for patients,
46:21using specifically
46:23GemOx
46:24plus lenvatinib
46:26and torapalumab.
46:27This is not a commonly
46:29used regimen when we think
46:30about the combination
46:31of this particular regimen, but,
46:33certainly,
46:34GemOx is a very known
46:36well known regimen in the
46:37setting of
46:39metastatic
46:40therapy in the biliary tract
46:41setting. And then we also,
46:43as we know, have evidence
46:44for immunotherapy
46:45in this setting as well.
46:47And furthermore, just to give
46:48you a little bit of
46:49history, it builds upon prior
46:50work that this team had
46:52established looking at this regimen
46:53for patients, but more so
46:55in the unresectable
46:56setting trying to convert these
46:59patients.
47:00This particular study, however, it
47:02enrolled one hundred and seventy
47:04eight patients as I have
47:05listed here, specifically
47:06looking at patients with high
47:08risk intrahepatic cholangiocarcinoma.
47:11And patients or, actually, those
47:13in the audience may consider,
47:14well, what is high risk?
47:15And that has been in
47:17this study and oftentimes other
47:18studies defined as a large
47:20tumor size,
47:22multifocal disease,
47:23vascular invasion,
47:25hepatic portal lymphadenopathy
47:27or lymph nodes, I should
47:28say,
47:29or increased CA nineteen nine,
47:33which I previously reviewed when
47:34I first started discussing prognostic
47:36factors. So you can certainly
47:37see the overlap.
47:39Patients were randomized to receive
47:41neoadjuvant
47:42gulp, which I just reviewed
47:44that regimen,
47:45versus upfront surgery. And all
47:47of the patients enrolled
47:48were then treated with eight
47:50cycles of adjuvant capecitabine.
47:52The primary endpoint for this
47:54study was event free survival.
47:57And I think what's really
47:58important is that it's the
47:59first randomized study to show
48:01evidence for new adjuvant therapy
48:03in this particular clinical space.
48:09The results are shown here,
48:11sharing the Kaplan Meier as
48:12you can see in the
48:13bottom right, but a hundred
48:14and seventy eight patients were
48:15randomized as I mentioned,
48:17and eighty eight patients were
48:18randomized to the neoadjuvant
48:20group. Important to know when
48:22reviewing the table one that
48:23there was an overall even
48:25distribution
48:26of the characteristics
48:27in each of the arms
48:28as far as the characteristics
48:30specifically
48:31considering stage,
48:32CA ninety nine, performance status,
48:35and tumor characteristics.
48:38One may ask, well, how
48:39many of the patients actually
48:41completed the neoadjuvant therapy? And
48:43it's important to note that
48:44ninety four percent of the
48:45neoadjuvant group actually did complete
48:47all of the planned cycles.
48:50The median event for event
48:52free survival or EFS was
48:54eighteen months in the neoadjuvant
48:55group compared to eight point
48:56seven in the patients that
48:58had upfront surgery,
49:00and the overall survival was
49:01seventy nine percent in the
49:02neoadjuvant group compared to sixty
49:04one percent of those that
49:06went to upfront resection.
49:08So what are the takeaways?
49:10Ultimately,
49:11I think that we are
49:12now starting to see data
49:14that there certainly can be
49:15a role for considering neoadjuvant
49:17therapy for patients with high
49:19risk intrahepatic cholangiocarcinoma,
49:22and, ultimately, further studies are
49:24needed.
49:26With that being said,
49:28for those that are here
49:29practicing in our area, we
49:30certainly have an open clinical
49:32trial that I would encourage
49:33you that if you have
49:34any patients that meet these
49:36criteria,
49:37that we do have a
49:38open study, which is under
49:40the PI of doctor Raghav
49:41Sundar, one of our medical
49:42oncologists and experts here, which
49:44is a phase two trial
49:45that evaluates the role of
49:47JEM Systerva
49:48as neoadjuvant
49:50therapy for high risk intra,
49:52intra intrahepatic
49:54cholangiocarcinoma.
49:56And similar to the overlap
49:57of what I reviewed for
49:58the NEOGOLD study when considering
50:01the high risk features, In
50:02this study, high risk is
50:03considered as greater than
50:06five centimeters greater than or
50:07equal to five centimeters as
50:08far as the tumor size.
50:10Is there any multifocality
50:12of the disease,
50:13vascular invasion,
50:15suspected or confirmed lymph nodes,
50:17a CA nineteen nine greater
50:19than two hundred.
50:22And here I have the
50:23study schema really just showing
50:24that the role of the
50:26near or how it is
50:27actually operationalized
50:28with four cycles prior to
50:30and four cycles after.
50:37In addition,
50:38we've besides talking about neoadjuvant,
50:41there is certainly the role
50:43that has been further explored
50:44of what the role of
50:46adjuvant therapy is.
50:48As mentioned by probably all
50:49of us at this point,
50:51biliary tract cancer certainly are
50:53associated with a poor prognosis,
50:54and the rate of recurrence
50:55is rather high up to
50:57or greater than fifty percent.
50:59So adjuvant therapy certainly has
51:01been recommended, which is really
51:02guided by patient
51:04comorbidities,
51:05their preference, and then also
51:07recovery from surgery.
51:13There have been few adjuvant
51:14studies evaluating the role of
51:16adjuvant therapy for biliary tract
51:18cancer. Many of these studies,
51:19however, we should note have
51:21been small. They've also been
51:22nonrandomized,
51:23and many have also been
51:25retrospective.
51:26But our clinical decision for
51:28using capecitabine
51:29in the adjuvant setting is
51:30really largely guided by the
51:32BILCAP study.
51:35As you can see here,
51:37within the e NCCN guidelines,
51:40adjuvant capecitabine
51:42is recommended and is considered
51:43a category one recommendation,
51:45and this is an ultimate
51:47decision
51:48from the data from BILCap.
51:50And I will review that
51:51because many in the room
51:52may say, well, the results
51:53from BILCap were limited as
51:55far as what the actual
51:56intention to treat results were,
51:58and I will review that.
52:03Described here, the BILCAP study
52:05was a phase three randomized
52:06study ultimately evaluating the role
52:09of adjuvant capecitabine
52:10versus observation in patients that
52:12had undergone resection for biliary
52:14tract cancers.
52:16Foraging forty three patients were
52:17part of this study, and
52:18they ultimately were randomized to
52:20either adjuvant
52:21capecitabine with eight cycles versus
52:23observation,
52:24and the primary endpoint was
52:26overall survival.
52:30The takeaway is, which is
52:32what leads to the controversy
52:33as far as do we
52:34recommend adjuvant case, cytobine,
52:37or do we not?
52:39I've listed the amount of
52:41patients randomized as I just
52:42recently reviewed, And I also
52:44want to note similarly to
52:46the NeoGOLD study that the
52:47patients were overall matched in
52:49regards to ECOD
52:50tumor characteristics.
52:53A little bit over half
52:54of the patients completed all
52:56the planned cycles.
52:59The recurrence free survival did
53:01favor the treatment group, which
53:03I think is important to
53:04know.
53:05But the endpoint, again, which
53:07was overall survival, did not
53:08reach statistical significance in the
53:10patients for the inpatient to
53:12treat, which I have noted
53:13here as far as the
53:14data.
53:15But the endpoint for overall
53:17survival
53:17and the protocol
53:19actually did. So I think
53:21as far as when we
53:22were thinking about this for
53:23the per protocol analysis,
53:25this is what ultimately contributes
53:27to
53:28us still recommending
53:30adjuvant capecitabine
53:31and also understanding that, again,
53:33these patients have high recurrence
53:35risk, and we have limited
53:36data for alternative therapies.
53:42When discussing
53:43with our patients, I think
53:44it should be a shared
53:45decision making, really thinking about,
53:47do they have any other
53:48comorbidities,
53:49DPD,
53:50and all of the things
53:51that will ultimately guide our
53:53decision to recommend
53:55adjuvant capecitabine.
54:00I'll briefly review chemo radiation
54:03because some may say, well,
54:04what happens if after surgery,
54:06after doctor Sogawa discussed surgery
54:08that there's an r one
54:10resection,
54:11so positive resection margin. So
54:13there are some patients that
54:14we may have a shared
54:15decision making, multidisciplinary
54:17tumor board to discuss the
54:19role of adjuvant chemoradiation.
54:22For the sake of time,
54:23I won't go into the
54:23greatest detail, but I think
54:25things to consider for your
54:26patient population when considering,
54:29should I
54:30actually recommend
54:31chemoradiation
54:32is is there no positivity?
54:35Is there positive resection margin?
54:37And then ultimately, shared decision
54:38making.
54:42Additionally,
54:44earlier, I believe doctor Strazzabasco
54:46may have mentioned,
54:47hepatic arterial infusion.
54:50And I think, ultimately,
54:51for this particular patient population,
54:55high risk of recurrence,
54:57poor prognosis, it's really important
54:59to consider what are the
55:01other therapies that we can
55:02consider in this particular setting,
55:05especially in the perioperative management.
55:07And I'll make sure to
55:08save a little bit of
55:09time because I know doctor
55:10Zhang will also discuss this
55:11as well.
55:13But when we think about
55:15HAI specifically,
55:16we ultimately think about what
55:18the role of this is.
55:19So when we think about,
55:21floxiridine
55:22or FUDR,
55:23which is a metabolic intermediate
55:25of five f u, it's
55:27infused through the hepatic arterio,
55:29and it has a ninety
55:30percent first pass hepatic extraction
55:32rate. That's really important when
55:33we're thinking about intrahepatic cholangiocarcinoma,
55:36which which is why this
55:38is used in HAI.
55:40And this is possibly what
55:41contributes to the overall potential
55:43to convert patients to resectable
55:45status so we can get
55:46them to doctor Sogawa
55:47and also to ultimately contribute
55:49to improving survival.
55:51The limitations of the current
55:53data ultimately do, they're limited
55:55in the space of the
55:56fact that we don't have
55:56nonrandomized
55:57studies,
55:58which really could strengthen our
56:00overall recommendation for considering HAI.
56:03But despite this, this is
56:04certainly an option to consider
56:06for your patients that could
56:07potentially be considered for resection
56:10through ultimate conversion.
56:13And these are the patients
56:14that you would want to
56:15think about as long as
56:16they don't have any extra
56:17hepatic disease,
56:19if they have preserved functional
56:20status, of course, and preserved
56:22liver function.
56:26In summary,
56:28which many of us have
56:29already said,
56:30biliary tract cancers are certainly
56:32heterogeneous,
56:32and they require multidisciplinary
56:34management,
56:35hence our panel tonight.
56:37There's growing data to support
56:39neoadjuvant therapy, especially for our
56:41our high risk patients.
56:43It's really important to explore
56:44clinical trial patients, and, ultimately,
56:47further work is needed in
56:48this space.
56:49I now will transition to
56:51doctor Zhang who will end
56:52our discussion this evening
56:54discussing the role of metastatic
56:56disease and unresectable disease.
57:02Alright. Thank you so much,
57:03Jackie. Let me try to
57:04share my slides. Of course.
57:10Alright.
57:21Does that all look okay?
57:22That's perfect, doctor Dang. Okay.
57:24Great. Thank you so much,
57:25Jackie, for,
57:27that great transition. And, also,
57:28I'm very grateful to have
57:30the opportunity to speak tonight.
57:32Thank you for everybody for
57:33staying fit as well. So
57:35I'll be focusing on the
57:36management of metastatic biliary tract
57:38cancer from medical oncology perspective
57:41with emphasis on systemic therapy,
57:43molecular profiling,
57:45as well as treatment sequencing.
57:47And then we'll also talk
57:48about a few practical issues
57:50that come up in real
57:51world care.
57:54I have no relevant disclosures.
57:58So this is a brief
57:59outline of how we're gonna
58:00approach the talk.
58:02I'll start with a brief
58:03case to frame the discussion,
58:05and then we'll review the
58:06molecular's landscape and biomarkers
58:08relevant to advanced disease.
58:11From there, I'll move through
58:12first and second line therapy
58:14and then discuss targeted therapy
58:16and sequencing.
58:17And we'll briefly touch on
58:19a selective role of hepatic
58:20arterial infusion,
58:22like Jackie did, and then
58:23close with some practical considerations
58:25and future directions.
58:28So ground to ground the
58:29discussion,
58:30I'll start with a patient
58:31of mine. This is the
58:33eighty three year old woman
58:34who came to me with
58:35advanced cholangiocarcinoma.
58:37Genomic profiling was obtained at
58:39diagnosis and identified an IDH1
58:42mutation.
58:43She started,
58:44standard first line therapy with
58:46gemcitabine,
58:47cisplatin,
58:47and darvalumab.
58:49I'll come back to her
58:50later, but first, I wanna
58:51review why that genomic result
58:53mattered.
58:55So we have seen this
58:57previously tonight, but one of
58:58the key concepts in advanced
59:00biliary tract cancer is that
59:01these tumors are molecularly heterogeneous
59:04and differ by subtype.
59:05Intrahepatic cholangiocarcinoma,
59:08which can be further classified
59:09into small duct and large
59:10ducts,
59:11is enriched before actionable alterations
59:13such as IDH one mutations
59:15and FGFR
59:16two fusions,
59:17whereas extrahepatic
59:19disease, more often, Harper KRAS,
59:21TP fifty three, and HER2
59:23alterations.
59:24So the importance of this
59:25is not just biologic classification.
59:28In the metastatic setting, it
59:30directly influences the molecular testing
59:33and ultimately the treatment options.
59:35So once we recognize that
59:37these tumors differ molecularly,
59:39the next practical question is
59:41how we identify those differences
59:42in clinic.
59:45So in practice, c ninety
59:47nine is commonly followed, but
59:49it has important limitations.
59:51It is not useful for
59:52screening, and its role is
59:54mainly prognostic
59:55and in following trends over
59:56time.
59:57An important limitation for CA99
60:00diagnosis
01:00:01is that it's absent in
01:00:02about ten percent of individuals
01:00:03who lack the Lewis antigen.
01:00:06Additionally,
01:00:07elevated levels of these proteins
01:00:08may also be detected in
01:00:10individuals with biliary obstruction or
01:00:12other benign biliary disease.
01:00:15There's a lot of interest
01:00:16in emergent biomarkers such as
01:00:18cell free DNA, circulating RNA,
01:00:21extracellular
01:00:21vesicles, and metabolomics.
01:00:24But at this point, those
01:00:25remain investigational.
01:00:27So for treatment decisions today,
01:00:29tissue based NGS remains the
01:00:31standard, and ideally, it should
01:00:33be obtained early in metastatic
01:00:34disease.
01:00:36So with that framework in
01:00:37mind, I'll move into first
01:00:39line treatment where the standard
01:00:40has changed meaningfully in the
01:00:42last few years.
01:00:45So for more than a
01:00:47decade, cisplatin and gencitabine remain
01:00:49the backbone of first line
01:00:50therapy after ABC zero two.
01:00:53The major recent advance has
01:00:54been the addition of immunotherapy.
01:00:57So here we talk about
01:00:58the TOPAS one trial, which
01:00:59established darvelumab plus gemcitabine and
01:01:02cisplatin
01:01:03as the new first line
01:01:04standard,
01:01:05with a median overall survival
01:01:06of twelve point nine months
01:01:08versus eleven point three months
01:01:09and a hazard ratio of
01:01:11point seven six.
01:01:12The absolute benefit is modest,
01:01:14but it is meaningful,
01:01:16and it moved the field
01:01:17beyond chemotherapy
01:01:18alone.
01:01:20So not shown on this
01:01:21slide here is a second
01:01:22randomized phase three clinical trial,
01:01:24which is the Kino nine
01:01:25six six, which also supports
01:01:27additional
01:01:28addition of immune checkpoint inhibitor
01:01:30to Cisgene.
01:01:31In that trial, pembrolizumab
01:01:33or placebo was added to
01:01:35cisgene, which also improved overall
01:01:37survival in the pembrolizumab
01:01:39arm. So in practice, for
01:01:41most FIT patients, chemoimmunotherapy
01:01:43is now the default first
01:01:45line approach.
01:01:47But even with that advanced,
01:01:48outcomes remain limited,
01:01:50and many patients eventually require
01:01:52or consider for second line
01:01:53therapy.
01:01:56So in the second line
01:01:57setting, the ABC zero six
01:01:59trial established Fofox as a
01:02:01standard cytotoxic
01:02:02option
01:02:03after progression
01:02:05on first line therapy.
01:02:06The benefit again is modest
01:02:08with median overall survival of
01:02:10six point two months in
01:02:11the Fofox and active symptom
01:02:13control arm versus five point
01:02:15three months in the active
01:02:16symptom control only.
01:02:18So this is a practice
01:02:19defining study, but it also
01:02:21highlights a major unmet need
01:02:22in the disease.
01:02:24In real world practice, second
01:02:25line treatment is often more
01:02:27constrained than the trial setting
01:02:28was just.
01:02:32So clinically, Fofax remains the
01:02:34standard second line regimen.
01:02:37Liposomal
01:02:38irinotecan
01:02:39and five of you is
01:02:40also using some settings, but
01:02:42the data are mixed, as
01:02:43reflected by the NIFTI and
01:02:44NELIRIC trial, which show contradictory
01:02:47results.
01:02:48Importantly,
01:02:49only about half the patients
01:02:51ever reach second line therapy,
01:02:53which is one reason early
01:02:54molecular profiling matters so much.
01:02:57If actionable
01:02:58alterations identify upfront, they can
01:03:00create options at progression.
01:03:03And that leads to the
01:03:04next slide, which is that
01:03:05standard chemotherapy
01:03:06still leaves us with substantial
01:03:08limitations.
01:03:10So despite the progress we
01:03:12have made, the median overall
01:03:14survival for metastatic biliary tract
01:03:16cancer remains around a year.
01:03:18Second line chemotherapy
01:03:20offers limited benefit,
01:03:21and we still lack reliable
01:03:23benefit biomarkers for immunotherapy
01:03:25response.
01:03:27The majority of patients do
01:03:28not have currently actionable targets.
01:03:31So what this field needs
01:03:32is better predictive biomarkers,
01:03:34better sequencing
01:03:35strategies,
01:03:36and broader access to molecular
01:03:38testing and targeted therapies.
01:03:41So to show how early
01:03:42molecular profiling can change management,
01:03:44I'll return to the patient
01:03:45I introduced earlier.
01:03:48This patient initially responded to
01:03:50gemcitabine cisplatin and durvalumab,
01:03:53And this lasted for about
01:03:55six months. But then she
01:03:57developed progression with enlargement of
01:03:59the primary lesion and new
01:04:00intrahepatic
01:04:01metastasis.
01:04:03This is where the molecular
01:04:04result identified at diagnosis becomes
01:04:07clinically important.
01:04:08Because she had a known
01:04:09IDH one mutation,
01:04:11she had a rational targeted
01:04:13option available at progression.
01:04:17So now we'll take a
01:04:18look at targeted therapy and
01:04:20how it it fits into
01:04:21treatment sequencing in biliary tract
01:04:23cancer.
01:04:25About thirty to forty percent
01:04:27of patients with biliary tract
01:04:28cancer harbor actionable alterations.
01:04:31The two best established examples
01:04:33in intrahepatic disease disease or
01:04:34IDH one mutations and FGFR
01:04:37two fusions.
01:04:39For IDH one mutant disease,
01:04:40ivositanib
01:04:41is a approved targeted option
01:04:43and showed overall survival benefit
01:04:45despite substantial crossover.
01:04:48FGFR
01:04:49inhibitors such as pemigatinib and
01:04:51fudimbatimab
01:04:52have shown meaningful activity, and
01:04:54in selected patients, compared favorably
01:04:56with traditional second line chemotherapy.
01:04:59HER2 is particularly relevant in
01:05:01extrahepatic
01:05:02and gallbladder cancers.
01:05:04A very recent study from
01:05:05the Horizon BTC one study
01:05:08showed durable activity with zenidetimab
01:05:11in previously treated HER2 positive
01:05:13metastatic biliary cancer,
01:05:15with a confirmed response rate
01:05:17of about forty one percent
01:05:18and a median overall survival
01:05:20of fifteen months,
01:05:22which further supports HER2 as
01:05:23a meaningful target in this
01:05:25disease.
01:05:26BRAF V600E
01:05:28is another important, though less
01:05:29common target.
01:05:31So target therapy has become
01:05:32an important part of modern
01:05:34sequencing,
01:05:35not just an as a
01:05:36niche consideration.
01:05:39So in addition to the
01:05:40currently approved targets, there are
01:05:42also rare but actionable alterations
01:05:44and broader precision strategies
01:05:46that are beginning to shape
01:05:48how we think about sequencing.
01:05:51So these are the, rare
01:05:52but clinically relevant alterations, such
01:05:55as MSI high disease, NTRK
01:05:57fusions, and in selected cases,
01:05:59RET or NRG one fusions.
01:06:02In fact, patients with MSI
01:06:04high may greatly benefit from
01:06:06pembrolizumab
01:06:07treatment,
01:06:08as they are shown to
01:06:09have an oral response rate
01:06:10in the seventies,
01:06:12which is significantly higher than
01:06:13the response rates that are
01:06:15observed in patients with pancreatic
01:06:17cancer.
01:06:18Higher PD L1 expression may
01:06:20also correlate with slightly better
01:06:21outcomes,
01:06:22but this measure is not
01:06:24suitable to select patients.
01:06:26More broadly, we're moving beyond
01:06:28one mutation, one drug thinking,
01:06:30and more toward precision sequencing
01:06:32concepts,
01:06:33including sequential FGFR
01:06:34inhibition,
01:06:36resistance monitoring, and the possible
01:06:38use of liquid biopsy to
01:06:39guide subsequent therapy.
01:06:41The main point is that
01:06:43molecular testing will not just
01:06:44inform one treatment option, but
01:06:46the sequence of care over
01:06:48time.
01:06:50So this is the algorithm
01:06:52that I adapted from the
01:06:53recent nature review that provides
01:06:55a simplified overview of management.
01:06:57I'll focus on the right
01:06:59hand side, which pertains to
01:07:00advanced endometastatic
01:07:02disease.
01:07:03The first key step is
01:07:04comprehensive molecular profiling.
01:07:07Most FIT patients start with
01:07:08first line chemoimmunotherapy,
01:07:10and then at progression,
01:07:12management branches based on whether
01:07:14an actionable alteration is present.
01:07:17If it is, our target
01:07:18this therapy becomes the preferred
01:07:20next step.
01:07:21If not, second line chemotherapy
01:07:23remains a reasonable option.
01:07:25So this algorithm really highlights
01:07:27a central role of molecular
01:07:28profiling,
01:07:29not just as a diagnostic
01:07:31exercise,
01:07:32but as a decision point
01:07:33that determines subsequent lines of
01:07:35therapy.
01:07:38So although my focus is
01:07:39on systemic therapy, hepatic arterial
01:07:42infusions worth mentioning in selected
01:07:44patients with unresectable
01:07:46liver confined intrahepatic cholangiocarcinoma.
01:07:49In a systemic review, response
01:07:51rates were about forty one
01:07:53percent with a median PFS
01:07:55of ten months and OS
01:07:56of just over twenty one
01:07:57months.
01:07:59Most recently,
01:08:00the Dutch pump two phase
01:08:01two study in JCO
01:08:04evaluated
01:08:05the
01:08:06HAI HAE pump with concurrent
01:08:07gemcitabine and cisplatin
01:08:09and asked support for this
01:08:11approach in carefully selected patients.
01:08:13This is not a routine
01:08:15option for most patients with
01:08:17metastatic disease, but it is
01:08:19reasonable to consider at experience
01:08:21centers with multidisciplinary
01:08:23review.
01:08:27So in practice, treatment decisions
01:08:29in metastatic
01:08:31biliary tract cancers are shaped
01:08:33not only by biology, but
01:08:35also by real world factors.
01:08:37Candidate selection depends on performance
01:08:39status, organ function,
01:08:41disease distribution,
01:08:42and molecular profile.
01:08:44Access barriers are also very
01:08:46real, including delays in referral,
01:08:48limited availability of comprehensive NGS,
01:08:52and unequal access to targeted
01:08:53or liver directed therapies.
01:08:56Because benefit is
01:08:57often modest beyond first line,
01:08:59quality of life and patient
01:09:00goals should remain central.
01:09:02And finally,
01:09:03multidisciplinary
01:09:04care and patient advocacy
01:09:06are often essential in navigating
01:09:08these complex decisions.
01:09:11So So looking ahead, the
01:09:12field is continuing to evolve
01:09:13beyond the current approved targets.
01:09:16There are multiple novel targets
01:09:18and strategies under investigation,
01:09:20including KRAS directed therapies,
01:09:23expanded HER2 strategies,
01:09:25claudan eighteen point two, and
01:09:27MDM two.
01:09:28At the same time, we're
01:09:29also seeing increased interest in
01:09:31combination approaches,
01:09:32resistance informed sequencing,
01:09:34and liquid biopsy guided strategies.
01:09:38Many of these remain investigational,
01:09:40but the broader direction is
01:09:41clear.
01:09:42We're moving toward increasing individualized
01:09:45therapy supported by molecularly selected
01:09:47trials.
01:09:49So to close, these are
01:09:50the main points I hope
01:09:51you'll take away.
01:09:53So to summarize, first, chemoimmunotherapy
01:09:56is now the first line
01:09:58standard for most FIT patients
01:10:00with metastatic biliary tract cancer.
01:10:03Second, early molecular profiling is
01:10:05essential to identify actionable alterations
01:10:08and to guide later sequencing.
01:10:11Third, targeted therapies have meaningfully
01:10:13expanded options beyond chemotherapy for
01:10:16selected patients.
01:10:17And finally,
01:10:19patient selection,
01:10:20access, and multidisciplinary
01:10:22care remain critical in translating
01:10:24these advances into real world
01:10:26practice.
01:10:28This remains a very challenging
01:10:29disease, but precision oncology is
01:10:31clearly changing how we approach
01:10:33it.
01:10:34Thank you.
01:10:37Thank you so much, doctor
01:10:38Zhang, for wrapping it up
01:10:39and just really making sure
01:10:41we really understand that so
01:10:42much has evolved in this
01:10:44space, especially for options for
01:10:45our patients and the need
01:10:46for tumor profiling
01:10:48early to offer additional options
01:10:50after progression on first line
01:10:52therapy. Thank you so much.
01:10:54I noticed that we do
01:10:56not have any questions in
01:10:57the chat, and I noticed
01:10:59that we also have gone
01:11:00over an hour, but
01:11:02just for some multidisciplinary
01:11:04discussion, given that it's rare
01:11:06that all of us are
01:11:07here together, I figured I
01:11:08allow us to at least
01:11:09have time for some few
01:11:11moments of discussion to maybe
01:11:12generate some questions. And if
01:11:14not, we can end the
01:11:15night.
01:11:16But I'll start off, and
01:11:18I'll ask doctor Sogel a
01:11:19question for you. You reviewed
01:11:23the actual criteria for considering
01:11:26patients for transplant, and I
01:11:28wanted to know if you
01:11:29could discuss what are some
01:11:31common barriers
01:11:32that may reduce the overall
01:11:34equitable approach for transplant for
01:11:37these patients.
01:11:39Well, I think,
01:11:41one thing that we don't
01:11:42know is,
01:11:44somebody who is a resection
01:11:46candidate
01:11:47and,
01:11:49is a transplant will be
01:11:50a beneficial or not. We
01:11:51don't have any trials.
01:11:53So,
01:11:54like, in like, about cerebrocarcinoma,
01:11:57for example,
01:11:58you know, that's also something
01:12:00similar too. When you have
01:12:01a liver resection, it's it's
01:12:03it's available.
01:12:04We
01:12:05tend to go into liver
01:12:06resection if it's liver is,
01:12:09liver function is remain.
01:12:12And but outcome is, generally
01:12:15speaking, actually, transplantation
01:12:17have as a better survival,
01:12:20than the resection if it's,
01:12:21you know, if it's in
01:12:23so, it's good within the
01:12:25Meran's criteria.
01:12:26However, utility of, you know,
01:12:28liver trans you know, or,
01:12:30you know, scarcity of, organs.
01:12:32And then so, therefore,
01:12:33most of our practice,
01:12:36generally, if it's somebody who
01:12:37is a resection candidate, we're
01:12:39going for resection
01:12:40rather than the transplantation. So
01:12:42that's part certainly, we need
01:12:44to have a more clarity
01:12:46for this.
01:12:47And,
01:12:49what I see more and
01:12:50more patient who's, for the
01:12:52chorangio,
01:12:53was found at is the
01:12:54latest stage of age.
01:12:56So,
01:12:58you know, age is not
01:12:59necessarily be a it's a
01:13:01biological age is more important,
01:13:03but
01:13:04not too many people who
01:13:06can go for liver transplantation,
01:13:08like a later of seventies
01:13:10or eighties.
01:13:11It's very hard to do
01:13:12a liver transplantation.
01:13:14So that's that's another,
01:13:16limitation.
01:13:18Number three would be,
01:13:22particularly,
01:13:24above three centimeter.
01:13:26Even you have,
01:13:27downstaging,
01:13:29be able to give a
01:13:30chemo,
01:13:32may potentially get the exception
01:13:34point. However, it's not the
01:13:36automatic exception.
01:13:37So the only,
01:13:39possibility, a living donor. So
01:13:41not not everyone can have
01:13:43a living donor. So that's,
01:13:47limitation
01:13:48of at this moment.
01:13:51Thank you.
01:13:52Doctor Strzad Bosco, this is,
01:13:55a question for you and
01:13:56really thinking about potential audience
01:13:58members.
01:13:59What are ways that
01:14:01oncologists
01:14:03can better partner
01:14:04with hepatologists
01:14:06to ultimately
01:14:07improve the outcomes for our
01:14:09patients diagnosed with biliary tract
01:14:11cancers?
01:14:15Oh, you're muted, doctor Strassbosco.
01:14:20Can you hear me now?
01:14:22Yes. I can.
01:14:23Well, I think that that
01:14:25it's a it's a it's
01:14:26a very,
01:14:27stronger and daily partnership, to
01:14:30be honest.
01:14:31Hepatologists
01:14:33are the one that,
01:14:34probably diagnosing
01:14:36more,
01:14:38intraepartic cholangiocarcinoma,
01:14:41and
01:14:42so we,
01:14:44receive the patient.
01:14:46We,
01:14:48kind of work up the
01:14:49patient reaches the anguities. But
01:14:51then after that,
01:14:53it's, it's, it's really teamwork,
01:14:56between,
01:14:57oncology,
01:14:59surgery.
01:15:01Intervention, radiology.
01:15:04And,
01:15:05you know, these cases are,
01:15:07of course, less, frequent than
01:15:09hepatosarcosinoma,
01:15:10but I think that with
01:15:11the hepatosarcosinoma,
01:15:12we are very well
01:15:14oiled and integrated
01:15:17multidisciplinary
01:15:20tumor board and and and
01:15:22and approach.
01:15:24And thinking about
01:15:25the,
01:15:28transplant for,
01:15:30intraparticle angiocarcinoma,
01:15:33it seems to me
01:15:35that there is a there
01:15:36is a clear,
01:15:38clear patient where this may
01:15:39be indicated. Right? So, you
01:15:41know, as we discussed, many
01:15:43patient with
01:15:45cholangiocarcinoma,
01:15:47they have steatotic liver disease.
01:15:49Sometimes they they have, cirrhosis.
01:15:52This patient, particularly if they
01:15:54are diagnosed with small,
01:15:56small,
01:15:57tumor, they are
01:15:59difficult to be resected.
01:16:01And,
01:16:04maybe this patient also,
01:16:06a little more compromised.
01:16:08So
01:16:09immunotherapy
01:16:11adjuvant is not something that
01:16:12you think about, but they
01:16:13could very easily be treated
01:16:16by local regional
01:16:18treatment and go down immediately,
01:16:20go down the the transplant,
01:16:23way, for example. Right? So
01:16:24we see the patient with,
01:16:27downstage the tumor. We we
01:16:29we buy
01:16:30time, and that is key.
01:16:32It's very important.
01:16:34And then we try to,
01:16:36to to to transfer the
01:16:37patient. And in in this
01:16:39phase also,
01:16:40medical oncology comes in as
01:16:42we discussed, particularly
01:16:43if this tumor are larger
01:16:45than two centimeter with, with
01:16:47an adjuvant treatment.
01:16:51So
01:16:52it's it's very difficult to
01:16:54say
01:16:55where they are the boundaries,
01:16:56honestly,
01:16:58of these different
01:17:00professionals
01:17:01that are working together,
01:17:07to provide the best treatment
01:17:08for our patients.
01:17:14Thank you so much, doctor
01:17:15Strazzavasco. I think we have
01:17:17one question in the chat,
01:17:18so I appreciate,
01:17:19that one question being put
01:17:21in the chat. And that's
01:17:22specifically
01:17:23about the NEOGOLD study. I
01:17:24think you raise a certainly
01:17:26a good point regarding this
01:17:28recently published,
01:17:29study,
01:17:30which,
01:17:31again, is the first study
01:17:33in this particular space.
01:17:35There's certainly as we get
01:17:37further and out further out
01:17:38as far as thinking about
01:17:40about forty two to forty
01:17:41eight months as far as
01:17:43where those tells are closely
01:17:44meeting, which is ultimately what
01:17:46you're alluding to.
01:17:47I think
01:17:49that tells me that we
01:17:51just need more information.
01:17:52You know, the study was
01:17:54a Chinese study, which means
01:17:55that I think it would
01:17:56be also helpful to have
01:17:57this study done similarly here
01:18:00in Western countries,
01:18:02but I don't think that
01:18:03it shows us that we
01:18:04should not consider neoadjuvant therapy.
01:18:07I think it just ultimately
01:18:08shows us that more work
01:18:10is done. More work is
01:18:11done. If I can add
01:18:12if I can add a
01:18:14a general consideration about the
01:18:15taste of the government mayor
01:18:18is the fact they are
01:18:20very tricky
01:18:21because you should look also
01:18:23at the
01:18:24how the cases
01:18:26decrease.
01:18:28Some of the some of
01:18:29the,
01:18:31trial that was shown at
01:18:32the end that the two,
01:18:33three patient on the on
01:18:35the later stages. And so
01:18:38how significant can they be?
01:18:41Yeah. I think.
01:18:43So many many trials failed
01:18:45the test of the of
01:18:46the tails,
01:18:48but
01:18:49how significant that is is
01:18:51is is a is a
01:18:52question that I always ask
01:18:53myself
01:18:54Yeah. Because the number of
01:18:56patient are certainly not the
01:18:57number that for which the
01:18:58study has been designed.
01:19:02Doctor Zhang, I think I'll
01:19:04end with asking you one
01:19:05question before we wrap up
01:19:07for the evening.
01:19:08But and we can kinda
01:19:09discuss this together as well.
01:19:11But one question I often
01:19:12think about when I'm thinking
01:19:14about our patients that have
01:19:15undergone resection,
01:19:16and now they're coming to
01:19:18us and referred by surgery
01:19:20to discuss the role of
01:19:21adjuvant capecitabine.
01:19:24What limits you from offering
01:19:26adjuvant capecitabine
01:19:28or what says I'm absolutely
01:19:30going to do it versus
01:19:32every patient I recommend adjuvant,
01:19:34Kate?
01:19:35Yeah. Great question. So in
01:19:37general, yes, for patients after
01:19:39upfront chemo resection,
01:19:41adjuvant keeps sit sitavine remains
01:19:43a standard based on the
01:19:44BILCAT trial.
01:19:46Assuming that they have recovered,
01:19:47you know, adequately from the
01:19:49surgery and also enough fitness
01:19:51for the treatment.
01:19:52But in practice, you know,
01:19:54the decision has been visualized
01:19:55based on margin status, nodal
01:19:57status,
01:19:58like, performance status, and patient
01:20:00preference too. I think I
01:20:02really appreciate your point during
01:20:04the talk about, you know,
01:20:05patients having high risk of
01:20:06recurrence, and currently, we don't
01:20:08have many other alternatives. You
01:20:10know? So that's something you
01:20:11present upfront with them and
01:20:12also the modest benefit.
01:20:15But in general, I think
01:20:16in the absence of, you
01:20:17know, definitive, like, the fit
01:20:19like, lack of fitness or
01:20:20preference, I would still offer
01:20:22it to most patients.
01:20:24I agree with you. And
01:20:24I think, you know, this
01:20:26is one of those conversations
01:20:27that
01:20:29share decision making. I, you
01:20:31know, review the data with
01:20:32them and show the limitations
01:20:34as NCCN.
01:20:35In their footnote, they highlight,
01:20:37you know, what happened as
01:20:39far as the intention to
01:20:40treat versus per protocol results.
01:20:43But as you alluded to,
01:20:44doctor Zhang, ultimately,
01:20:46we don't have any other
01:20:47alternatives.
01:20:48You know, it's not like,
01:20:49okay. Well, I can offer
01:20:50this instead. And what we
01:20:51do know, which is what
01:20:52I often share with, my
01:20:54patients, is that there's such
01:20:55a high risk of recurrence.
01:20:57And, ultimately,
01:20:58when we think about capecitabine
01:21:00compared to, let's just say,
01:21:02FOLFOX or some other
01:21:04more multi agent regimen,
01:21:06there's less toxicities
01:21:08associated with it depending on
01:21:09what their comorbidities
01:21:11are, DPD testing, etcetera.
01:21:13So I certainly agree with
01:21:14you.
01:21:16If there are no other
01:21:17questions in the chat, which
01:21:19it does not look like
01:21:20it is, I first want
01:21:21to thank my panelists
01:21:23for speaking this evening, for
01:21:25taking time to
01:21:27educate our community
01:21:28and coming together. And I
01:21:30also want to thank all
01:21:31of the
01:21:32guests that came tonight or
01:21:34will come later,
01:21:35and for all of those
01:21:36that helped organize this event.
01:21:38Thank you so much for
01:21:39joining. Have a good evening.
01:21:41You, Kylie, Jack Jackie, for
01:21:43making this
01:21:45beautiful panel.
01:21:46Of course. Thanks.
01:21:48Thank you. Bye. Thank you
01:21:49so much. Good