Center for GI Cancers CME Webinar Series: Biliary Tract Cancer

Transcript

• 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