Center for Gastrointestinal Cancers CME: NETS

March 18, 2022

March 17, 2022

Presentations by: Drs. Pamela Kunz, Sajid Khan, and Mariam Aboian

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00:00So welcome everyone,
00:01my name is Doctor Pamela Koons
00:03and I am a GI medical oncologist.
00:05I am the director of the Center for
00:09Gastrointestinal Cancers at Yale Cancer
00:11Center and Smilow Cancer Hospital.
00:13This is our kickoff for
00:15our spring CME series.
00:17For the Center for GI cancers we are
00:19starting tonight on neuroendocrine tumors
00:21and I will be your host on Thursday,
00:24April 21st.
00:24We will have a CME on rectal cancer
00:27hosted by Doctor Michael Cicchini,
00:29and on Thursday, May 19th.
00:31We will have a CME on gastric
00:33cancers hosted by Doctor Jill Lacy.
00:38So this evening I have the pleasure
00:41of hosting and moderating this
00:44talk on neuroendocrine tumors.
00:46I will be giving a brief overview of Nets
00:49101 and then we'll help moderate the Q&amp;A.
00:52I'm joined by Doctor Miriam,
00:53a boy and an assistant professor
00:56of radiology and nuclear medicine,
00:58and she will be speaking about
01:00the role of molecular imaging and
01:02theranostics in care of patients with
01:04Nets and doctor Saj Khan and associate
01:07professor of surgery and surgical.
01:09Allergy and Section chief
01:11of Hepato Pancreato,
01:12biliary and mixed tumors will be
01:14joining us this evening and talking
01:17about the surgical management
01:18of pancreas and small foulness.
01:21So I will just go ahead and get started,
01:23so I'm just for our audience.
01:25Each of our talks will be about 20 minutes.
01:27Please feel free to put questions
01:29in the chat or Q&amp;A throughout.
01:32We will try to respond with
01:34a typed response throughout,
01:36but we will also have time at the end
01:39for a through Q&amp;A and you can ask them.
01:42These are my disclosures,
01:45so I'm going to talk briefly about the
01:47epidemiology and nomenclature of Nets.
01:49Talk about characteristics that I
01:51think really impact treatment selection
01:54for patients and then talk about
01:56treatment for hormone and tumor control.
01:59I usually like starting with a little
02:01bit of history so neuroendocrine
02:02tumors and the description of
02:05Nets goes back to the late 1800s,
02:08and it was really in the early 1900s that.
02:11Doctor Urban door for a German
02:14pathologist coined the term carcinoid.
02:17It meant cancer like and he described
02:19and felt that there were five key
02:21characteristics that they were.
02:23These tumors were small and multifocal
02:26had undifferentiated cellular formations,
02:28had well defined borders,
02:30no metastatic potential,
02:31and were slow growing and harmless,
02:33and though he contributed really important
02:36early knowledge about this disease,
02:39we now know that many of these
02:41characteristics are not true.
02:43And I think the term carcinoid
02:46and cancer like, unfortunately,
02:47really slowed the field in terms of our
02:51recognition that these are in fact cancers.
02:53The term carcinoid is really fallen
02:55out of favor and instead we are
02:58using the term neuroendocrine tumor
03:01and then by which primary site.
03:03So we have seen an explosion of advances,
03:06both therapeutics and diagnostics
03:09really since 2011.
03:10So in the 1980s we had strept
03:13Zosyn and Ivy alkylating agent,
03:15and octreotide that was initially
03:18approved for hormone control,
03:20and then since 2011 we have had
03:23therapeutic advances in the areas
03:26of biologics of everolimus and snib
03:30somatostatin analogs of lanreotide
03:32to look just at for carcinoid.
03:34Syndrome, Ludo date in 2018.
03:37We'll talk about some of the.
03:39Other systemic agents and then also
03:42some of the imaging agents that
03:44are listed above the timeline.
03:46I like also sort of nailing down the
03:49point that Nets are really not that rare,
03:53so they are rare by incidents,
03:54so incidents being the number of
03:57patients diagnosed per year and for
04:00this is based on a large Sears study
04:03conducted in 2017 and the incidence
04:05rate for Nets is about 7 per 100,000
04:08and this is in the yellow line on the
04:10figure compared to the blue line,
04:12which is the incidence of all
04:14malignant neoplasms which has
04:15remained relatively stable.
04:17However, the the prevalence of
04:19neuroendocrine tumors is actually the
04:22second highest prevalent GI malignancy.
04:25It exceeds stomach and pancreatic
04:28adenocarcinoma combined,
04:29and that's likely because this is a
04:32more indolent disease and patients
04:34live for many years more commonly with
04:37the low grade neuroendocrine tumors.
04:39Nets are epithelial neoplasms
04:41derived from neuroendocrine cells
04:43throughout the body,
04:44most commonly found in the GI tract,
04:46but also in the lungs and other sites,
04:49and most grow slowly in comparison with
04:51their adenocarcinoma counterparts.
04:53The majority are sporadic and the
04:55minority are associated with familial
04:57syndromes such as me and 1,000,000 two.
05:00Von Hippel,
05:01Lindau and Neurofibromatosis
05:02pathognomonic for this disease is
05:05the fact that somatostatin receptors
05:07are present on the cell surface
05:09in about 80 to 90%.
05:10Of netson,
05:12this is typically with somatostatin
05:14receptor type 2.
05:16The diagnostic work up and I will
05:17say if you take away one thing from
05:20this is that the cross sectional
05:21imaging is really the mainstay of how
05:23we monitor the patients with Nets.
05:26Either a multiphasic CT and that
05:29arterial phase is critical if
05:31you're ordering a CT scan or an
05:34MRI somatostatin receptor.
05:35Imaging is important but is not
05:37the primary modality with which
05:39we image these patients.
05:40These are done commonly at time of
05:42diagnosis and for patients with
05:44metastatic disease we may do them.
05:46Annually or every two years,
05:48somatostatin receptor imaging
05:49is now used with gallium 68,
05:52dotatate pet or copper 64,
05:54and I'm going to actually.
05:55This will be a little bit of a teaser.
05:57I'm going to let doctor a boy
05:59and talk more about somatostatin
06:00receptor based imaging.
06:02The tissue diagnosis we like to
06:04know the primary site if we can
06:06identify it and four key data
06:08elements are important when you're
06:10looking at a pathology report.
06:12The Who grade Ki 67 mitotic index.
06:16Degree of differentiation.
06:17We'll talk about that in a moment.
06:20And then tumor markers or hormones
06:22are important for this disease,
06:24but I will say that tumor markers such
06:27as chromogranin or neuron specific
06:30enolase or pancreas statin often
06:32fluctuate and may not actually track
06:35with what's happening radiographically.
06:38The field has swung away from
06:41using these and I often don't use
06:44chroma granite a now because really
06:46the gold standard is the imaging.
06:48Hormones,
06:48however,
06:49such as serotonin or 24 hour urine 5 hiaa,
06:54which is a byproduct or a metabolite
06:56of serotonin.
06:57Those can be useful and should be
07:00tracked overtime.
07:02So I find that there are really six key
07:05characteristics that impact treatment
07:07hormone status stage and burden of
07:10disease grade and differentiation.
07:12Pace of growth,
07:14primary site and somatostatin
07:15receptor status.
07:16I'll spend just a moment on each
07:18of these just to really set
07:20the stage in terms of how we
07:21talk about and think about
07:23treatments for nuts.
07:24So a functional neuroendocrine tumor is
07:27defined as a patient who has symptoms
07:30from a measurable hormone that's
07:32in either the urine or the blood.
07:34Carcinoid syndrome is a
07:36classic example of that.
07:3810% of patients with small intestine
07:40Nets have carcinoid syndrome,
07:41and it's due to production of peptides and
07:44am means such as serotonin or five hiaa,
07:47and it can cause Flushing Venus
07:50telangiectasis as shown in this
07:52picture on on the left diarrhea.
07:54Bronchospasm, valvular fibrosis,
07:57and hypotension.
07:58This is also a picture of a of
08:01the pulmonary and tricuspid
08:03valves that are very fibrotic.
08:05Pancreatic neuroendocrine tumors can also
08:07secrete hormones in about 40% of patients,
08:11most commonly insulin,
08:13followed by gastrin,
08:15Glucagon and vaso intestinal polypeptide,
08:18and the symptoms are really defined by
08:20the hormones secreted and nonfunctional.
08:22Nets are defined as patients who are
08:25either asymptomatic or have symptoms
08:27that are not from hormone access.
08:32So stage and grade.
08:33I think this is I really try to
08:36describe this to patients 'cause
08:38I think for patients in particular
08:40this can be very confusing.
08:41So to this audience however,
08:44stage is very familiar term.
08:46What's interesting is that
08:48the AJC staging criteria have
08:50only included Nets since 2010.
08:53This is a really nice picture here
08:55of a localized pancreatic net,
08:57which will show in the video and
09:00a metastatic pancreatic net with
09:02high degree of liver burden.
09:04As you can see here,
09:05grade is really what the cells
09:07look like under the microscope.
09:08Low grade is slower,
09:10growing higher grade is faster growing.
09:12We really base this on the Ki
09:1467 in mitotic index.
09:16The 2019 digestive WHO
09:18classification is the most recent.
09:21I'm next to the Red Arrow is a.
09:23New change that was made to this
09:25so we have well differentiated.
09:27Net grade 1/2 and three and poorly
09:31differentiated nurkin carcinoma
09:33grade 3 and that's divided into
09:36small cell and large cell.
09:38When I didn't put on this slide
09:39is kind of the breakdown of the
09:41Ki 67 in mitotic index,
09:43but really the take away from
09:45this is that clinically we treat
09:47the grade one and two well
09:49differentiated Nets very similarly.
09:51This well differentiated grade 3
09:53net is a relatively new category.
09:56I think that we have to treat
09:58based on the individual patients
10:00biology bulk of disease.
10:02The poorly differentiated nerdacon
10:04carcinomas are treated very differently.
10:06That will not be the primary topic of.
10:09Kind of the subsequent slides on treatment.
10:11That's typically those patients are
10:13typically treated with platinum at openside.
10:16So pace of growth,
10:17something I was getting to really
10:18does inform our treatment selection.
10:19We may need a patient with a
10:21metastatic low grade net who has very
10:24stable disease or slow progression,
10:25or may have more rapid progression.
10:27Some of those patients may not
10:29need treatment initially.
10:31Observation may be appropriate,
10:33whereas others may have high burden
10:36of disease or symptoms from tumor
10:38bulk and they may need treatment.
10:41Primary site matters,
10:42I know this is a GI focused talk,
10:45but Nets can happen in almost any
10:47organ in the small intestine.
10:49Most commonly that is one of the most
10:52common sites we see commonly in the ilium,
10:55but we will also see pancreatic
10:57Nets and other Nets in the GI tract,
11:00and many clinical trials and treatments
11:02are really tailored based on primary site.
11:05Therefore,
11:05FDA approvals are sometimes limited
11:08specifically to primary sites.
11:10One example of that.
11:12Is synonym for pancreatic Nets.
11:15We now know that somatostatin
11:17receptor status is critical both
11:19for diagnosis and therapy.
11:21Again,
11:21I'm going to let Doctor boy and go into this.
11:24This is an interesting picture
11:25just to show an octreoscan which
11:27has now really completely been
11:29replaced by gallium dotate.
11:31This is the same patient image with an
11:34octreoscan and a gallium 68 dotate pet,
11:37and you can see that the resolution is
11:40far superior with the pet based imaging.
11:42So now we're going to launch in the next
11:45sort of the final half of my presentation
11:47on general treatment categories for nuts.
11:49I will go into some of the specifics
11:51just so that you have access to this.
11:53If you choose to watch this again,
11:56so we have 4 main categories,
11:58somatostatin analogs, peptide receptor,
12:01radionuclide therapy, biologics,
12:03and cytotoxic chemotherapy,
12:04I am going to really focus my conversation or
12:10presentation tonight on antitumor treatments.
12:14Just a brief comment that we know.
12:15So not a statin.
12:16Analogs were really initially developed
12:18for a hormone control and remain as the
12:20primary tool that we use for hormone control,
12:23but I'm not going to go
12:24into just for sake of time.
12:25Details on hormone control tonight,
12:28so somatostatin receptors
12:30and and theranostics again,
12:32I'm going to just use this to
12:33talk about some of the therapies.
12:35Dr Abovyan will go into this as well,
12:38but in terms of my cartoon here,
12:40imagine you have a patient in population
12:42for whom you would like to select out.
12:44Do they have a receptor on the
12:46surface of their cells?
12:47We do in fact have that.
12:49So with the gallium 68 or copper 64 pets,
12:52we select out those
12:53patients using that imaging,
12:54and then we in fact have a targeted
12:56therapy that goes to that target.
12:58So that's theranostics Dr.
12:59Boy and will focus on that.
13:01When I described this to patients,
13:03I used the lock and key
13:05description or analogy.
13:06I think that helps them understand
13:09why we use somatostatin analogs,
13:11why we use the Dota Tate imaging.
13:13So think of the somatostatin
13:15receptor as the lock, the.
13:17Key is the peptide,
13:20and then there's a reporting unit.
13:22So for somatostatin analogs,
13:24we actually have two trials that
13:27demonstrated antitumor effect.
13:29The Pro MID study demonstrated the
13:32effect of octreotide versus placebo,
13:34and the clarinet study demonstrated the
13:37effectiveness of lanreotide versus placebo.
13:39Both had a primary endpoint of of
13:43the permits that it was time to
13:45progression and that the clarinet
13:47study was progression free survival
13:48and they both should have benefit
13:50over placebo octreotide.
13:52Is not formally does not have a
13:55formal FDA label for antitumor effect.
13:58It is primarily in hormone control,
14:00but it is.
14:01These two agents are often
14:02used interchangeably.
14:03Landry Tide was FDA approved
14:05in 2014 as an antitumor agent.
14:10I'd like to put this up because I
14:11get asked this a lot. So how do we
14:13think about dosing for tumor control?
14:15Octreotide LARC is usually used at the
14:1830 milligram I am monthly dose and
14:21lanreotide at 120 milligrams deep. Subq.
14:23There is no need to overlap with short
14:27acting unless it's a functional tumor.
14:29I think there was data years ago that we
14:31needed to do a test dose to test for allergy.
14:34That's not generally needed in
14:36practice and there is little data
14:38to support the routine use.
14:40Above standard dose of somatostatin
14:42analogues for tumor control.
14:44The side effects include nausha, diarrhea,
14:47cholelithiasis, and hyperglycemia.
14:51I'm going to go through these quickly.
14:53I have them just kind of as placeholders,
14:54but Doctor Brian will talk about these,
14:56but we've had incredible advances in
15:00the diagnostics for Nets as well and
15:02there is a very handy paper and I have
15:05this here just as a reference on the
15:07appropriate use criteria for somatostatin
15:09receptor PET imaging and new under consumers.
15:13That's a great reference.
15:14And then in the therapy is something that
15:17also Doctor Boy and will discuss and
15:19specifically around the Netter one phase,
15:22three clinical trial.
15:23So I'll mention it just in passing
15:25that this was a study I had the
15:27opportunity to serve as a key.
15:28I when I was at Stanford.
15:30It's a randomized study that really
15:32set the stage for using their Gnostics
15:35and and specifically alluded it,
15:37and that's it.
15:38Was a positive study.
15:39I will give.
15:40I will give that punchline away
15:42for Doctor O'Brien.
15:43But moving on to some of the
15:45other systemic therapies,
15:45I will spend a few minutes on so.
15:48Everolimus is approved for pancreatic
15:50net and non functional GI and lung Nets.
15:53This is an inventory inhibitor.
15:56There were sister studies Radiant
15:58three and Radiant four and.
16:02Both of them showed a progression
16:04free survival benefit in
16:05these patient populations,
16:06and they were both approved.
16:08So for pancreatic net in 2011 and
16:11for GI and lung Nets in 2016.
16:14And tyrosine kinase inhibitors also
16:16have a role in neuroendocrine tumors.
16:18Sonett nib was approved on the
16:21basis of this randomized study in
16:23patients with well differentiated
16:25advanced pancreatic Nets.
16:26So that's the one that I said we don't
16:28yet have a tyrosine kinase inhibitor
16:31approved for small bowel Nets.
16:32This was also approved on the
16:34basis of a PFS benefit.
16:36You'll notice that most neuroendocrine
16:38tumor clinical trials have progression
16:40free survival as a primary endpoint,
16:42and that's because OS.
16:45Is an impractical endpoint given
16:47that patients tend to receive many
16:50subsequent therapies after these
16:52clinical trials and it be given
16:54the indolence of the disease,
16:56it would be too difficult,
16:57practically speaking,
16:58to use overall survival.
17:00So this was approved in 2011.
17:04Sir Afatinib is not yet FDA approved.
17:06It is under FDA review.
17:09At present,
17:09this was on the basis of two
17:11large studies conducted in China
17:13and then a phase one.
17:14Two study that has been
17:16conducted in the United States
17:18in a more traditionally Western population.
17:20But this was positive in both
17:23pancreatic and extra pancreatic Nets.
17:26And is, I suspect that at some
17:28point this spring or summer,
17:30we will have a decision from the FDA.
17:34I'd like to mention a study on
17:36chemotherapy that I had the opportunity
17:38to lead for pancreatic Nets,
17:40so this was a study of temozolomide versus
17:44capecitabine intimas Olumide for grade
17:46one or two metastatic pancreatic Nets.
17:49This was a study that ultimately
17:51demonstrated that Caped M was superior to
17:55temozolomide alone and median progression.
17:58Free survival was about 23 months
18:01for the combination versus 14 months.
18:04For Thomas Olumide at the time
18:06of the initial analysis,
18:08it appeared as if there was an
18:11overall survival benefit benefit.
18:13Stay tuned.
18:14We have the final analysis submitted
18:16to ASCO for an updated analysis.
18:20I think one of the key takeaways
18:22of this is that we see a higher
18:24response rate than we've seen really
18:26for any of the other therapies.
18:28I did not go into that,
18:29but somatostatin analogues, mtor inhibitors,
18:33tyrosine kinase inhibitors all have a
18:36you know 5% or less objective response rate.
18:39So for patients with pancreatic Nets
18:42who need objective tumor shrinkage,
18:44these are actually very good
18:46therapies to think about.
18:48So let's wrap this up.
18:50I think I have.
18:51Two slides left.
18:51So how do we really think about
18:53sequencing that these treatments?
18:54It's very confusing.
18:55We're actually in a fortunate place
18:57now of having a number of therapies,
18:59but it gets very difficult to know
19:00what order in which we should use them,
19:02so this is adapted from Nancy CN guidelines,
19:05so I would say commonly a first
19:07line treatment is either observation
19:10or octreotide or lanreotide,
19:12but where it gets very confusing as
19:14thinking about second line therapies.
19:16So I have a handy table to
19:18help you think about that,
19:19and I've put them in.
19:20Order of how I generally will think
19:23about using them.
19:24I often will consider using PRT or Ludo
19:27tape or lutathera as the as it's also
19:31called in the second line setting.
19:33It has a modest response rate of
19:35about 18% along PFS and is well
19:38tolerated and we do have to take care
19:41if patients GFR is less than 30 but
19:43we are developing more experience with them.
19:46The chemotherapy tamela mining capecitabine
19:49has the highest response rate.
19:51And should be considered for
19:53patients with pancreatic Nets who
19:55need an objective response.
19:57It does have higher adverse
19:58events for older patients.
20:00I will sometimes consider temozolomide alone.
20:03Forever Elemicin soon if they
20:05both have very low response rates,
20:06the PFS is about a year best for
20:09low volume disease,
20:10but I find that the adverse event
20:13profile is tough for both of these.
20:15Everyone ever really miss in
20:17particular is good for insulinoma
20:19because it can cause hyperglycemia,
20:21but it's tough and can cause
20:24pneumonitis and the hyperglycemia
20:25can be difficult for patients
20:28with uncontrolled diabetes.
20:29So takeaways I hope you've
20:31learned that Nets are not
20:32that rare. They are deserving
20:34of high quality basic,
20:35translational and clinical research efforts.
20:37We've had incredible advances
20:39in the last 10 years.
20:41PRT is really a game changer
20:42and I expect the next decade of
20:44clinical trials to be looking
20:46at better patient selection,
20:48minimizing toxicities and increasing
20:50efficacy and multidisciplinary care
20:52and team science is really key for this
20:56disease so I am going to stop share.
20:58I think I'm close to time.
20:59I am going to pass the baton to
21:02Doctor Abovyan and then Doctor Boyd
21:03if you can then pass that baton
21:05when you're done to Doctor Khan and
21:07then we will do a Q and a great.
21:16Thank you doctor Kuntz. This was fantastic.
21:19Sam my screen.
21:32So I'm going to talk about the
21:34role of molecular imaging,
21:36and there are Gnostics in the care of
21:38patients with neural neoplasms I'm in.
21:40I'm at Yale Department of Radiology
21:43and I am in a nuclear medicine
21:46and new radiology sections.
21:50For disclosures, I have a research
21:53collaboration with vistage imaging and I do
21:56clinical trials with Blue Earth diagnostics.
21:58We're going to start a little bit
22:00with standard imaging, CT, and MRI,
22:02but we're not going to focus on this
22:05imaging modalities because they're pretty
22:08well understood in the community and just
22:11kind of going over the basics of it.
22:14For carcinoid tumors, we can do very
22:17nice chest imaging with CT of the chest.
22:20We can do contrast and noncontrast imaging,
22:23and here is an example of
22:25a lung carcinoid lesion.
22:27For pancreatic neuroendocrine
22:29tumors we can do CT imaging.
22:34Enhance CT imaging,
22:35but we can also do MRI and here you
22:39see actually a patient with pancreatic
22:42tail or entropy neoplasm that is
22:45heterogeneous solid and partially cystic
22:47and you can see that it's actually
22:49sometimes difficult to evaluate.
22:53We can also do MRI imaging with
22:56abdominal MRI.
22:57You can do it with contrast
22:58and without contrast,
22:59and you can evaluate in this particular
23:04patient static liver lesions within the.
23:08This MRI pretty well and this actually
23:09is same patient that progressed in
23:11development has to season the liver.
23:15But we want to also start imaging
23:19beyond standard anatomical imaging
23:21with molecular imaging and with
23:24standard and understandable imaging
23:25we can see a lot of the basics of
23:28the of of the anatomy you can see
23:31actually delineate the borders of
23:32the tumor and where they're located,
23:35but it's really hard to say what is
23:38the characteristics of the tumor,
23:40so we're very good at defining the
23:42anatomy and the location and the extent
23:45of the disease and location of disease.
23:47But not so much in terms of is
23:49the same neuroendocrine tumor.
23:51If you just look at the lover?
23:52Or is this something else?
23:55What's really nice is that you can
23:58actually use targeted imaging to describe
24:01the receptors on the surface of tumors,
24:04and you can characterize these.
24:06Reset these unjust imaging
24:08without having to do a biopsy.
24:11And this is an example of
24:13a gallium dotatate PET,
24:14which I'll describe this little alphabet.
24:16So soup in the next few slides,
24:19but what it allows you to do
24:22is to visualize semantics.
24:24Some of some analog binding
24:27to a somatostatin receptor,
24:30and being able to see it light
24:32up on this Cam.
24:34I'm so glad Doctor Kunz mentioned
24:36that tree a scam that used to be
24:38the standard way of trying to see
24:41some exciting receptor receptor
24:43expression on tumors.
24:45And as you can see,
24:46these are not very good images
24:47and they're very hard to see.
24:50And it's very difficult to
24:51tell where the tumor is,
24:53and this is actually the same
24:54patient I showed you earlier.
24:56With pancreatic tail tumor,
24:58and you can barely see
25:01where this illusion is,
25:03and this is a planar imaging,
25:05and if we did SPECT,
25:07we could localize it to
25:09the left upper quadrant,
25:11but it would be very difficult to
25:14localize it to the pancreas very well.
25:16Also, if there were smaller lesions,
25:18we wouldn't be able to see it.
25:20And here's an example of a trio
25:23scan being lined up right next
25:25to door dotate scan gallium
25:28dotatate pet in the same patient,
25:30and you can see how many
25:32lesions are being missed.
25:33An actress can that can be
25:35clearly seen on the pet C team.
25:39But going to the dough depart a
25:43lot of folks ask me Doda what,
25:45what is this Doda and the alphabet soup
25:49of gallium dotatate gallium dooda talk
25:53lutetium dotatate usually confuses folks,
25:56but there's actually a very nice logic to it.
25:59So let's go over that,
26:01because then you will never question
26:04what what these are. So first,
26:07let's talk about labeling in chemistry.
26:10When you're thinking about pet pet
26:13radionuclides such as gallium and copper,
26:16which are used for imaging and pet,
26:18you cannot just attack,
26:20give them to the patient,
26:22they're actually toxic,
26:23so you need to keep them in the cage,
26:26and this is a doda cage,
26:28so you would kill 8 the
26:30gallium 68 in this doda cage,
26:33and what's really nice about this cage.
26:35It has a couple of.
26:36Four different arms and to these arms you
26:40can actually attach your targeting molecule,
26:43so in this case it's actually
26:45a tight analog Tate,
26:48so you attach this peptide to the
26:50doda and you have your radionuclide
26:53chelated inside of the Doda.
26:56So there's a very logical name to this.
26:59This value attach it through
27:01the ARM gallium Doda date.
27:03Very simple, right?
27:05So now that you understand.
27:07This kind of logic it it becomes very
27:10easy to understand how we mean these
27:13scans and with the labeling you can
27:17actually really be able to see this.
27:21So this is a gallium dotate PET CT in
27:24a patient with multiple metastases.
27:28Some medicine receptor positive liver
27:30metastases and you can actually see
27:32that there is also a period where
27:34did metastasis in the lymph node
27:36that's outside of the liver and
27:38here you have kidneys and bladder.
27:42So it really helps you evaluate
27:45the patients in terms of the
27:47appropriate use criteria.
27:48I'm so glad Doctor Kunz had a full
27:51slide on this in terms of evaluating.
27:54Not all patients need to be getting gallium
27:57daughter take pets and there's there.
28:01We're still truly evaluating exactly where
28:03and when we should be doing these scans,
28:07but there's several indications
28:10that should that that can.
28:12That are appropriate and some of
28:15the most most indicative are the
28:18initial staging after histologic
28:20diagnosis of neuroendocrine tumor
28:21and localization of primary tumor
28:24and patients 'cause there this.
28:26This skin is so sensitive form
28:28for for lesions,
28:29so you'll be able to see it and
28:32then the other very common.
28:34Very important point is selection
28:36of patients for some meta stat
28:38and receptive targeted therapy
28:40which we'll talk about it.
28:42Later now what's really nice about this
28:45therapy and this is where it's really
28:49revolutionary in medicine is that you
28:52can use this method to image your tumor,
28:55so you have your radionuclide.
28:57You have your cage and you
29:00have your targeting peptide,
29:01but then after you image the tumor,
29:04all you have to do is to pop this one
29:07out and pop lutetium 177 in so you keep.
29:12A molecule the same.
29:13You keep the targeting the same but.
29:18The radionuclide now is actually emitting
29:21beta particles that can can act as a
29:27therapeutic for neuroendocrine tumors.
29:29So this would be called very logically.
29:32I know you're you're thinking about this.
29:34Lu teach to Doda tape.
29:36There you go. Very simple.
29:39So we imaged with gallium dotatate
29:41and we treat it with lutetium
29:43dotatate and the only thing that
29:45changed was the radionuclide inside.
29:48So you know this drop whatever we imaged.
29:51That's exactly where the treatment went.
29:54Now we don't just have to do lutetium,
29:57we can also use other radionuclides
30:01such as alpha emitters and here
30:04at Yale we're now are approved to
30:06start doing this and it's very
30:08exciting new development to start
30:10doing these therapies in patients.
30:13So how do these alpha and beta emitters work?
30:17Well for lutetium and this is an image from.
30:23AAA a website where basically describes
30:27the mechanism of luthera and you
30:31administer the drug intravenously.
30:34The drug gets taken up into the
30:37neuroendocrine tumor sides.
30:38The drug binds to the receptors
30:40on the tumor sides and gets
30:42internalized inside of the cell.
30:44Through endocytosis and the radionuclide
30:48emits its particles beta particles,
30:51or if using that actinium type of therapy.
30:56Luther, it's really the beta
30:58particles because it's lutetium
31:00177 and that can cause DNA damage.
31:03And once you have DNA damage you can
31:05that can lead to tumor cell death.
31:08And that's and that's the main mechanism.
31:11So to just kind of overview this again
31:15in terms of image guided therapy,
31:17you can select patients for whether
31:20they are eligible for this kind of
31:23therapy with your imaging agent,
31:26gallium dotatate.
31:27And you can see if the patient expresses
31:30this amount of statin receptors in the body,
31:33and in this particular patient
31:35there are multiple metastatic lesion
31:37that can take up the targeting.
31:38Molecule,
31:39then you bring the patient in and
31:42you provide intravenous therapy.
31:44And that is basically the same
31:47as the imaging agent,
31:48except it has the radionuclide
31:50that causes DNA damage.
31:52And what's really interesting
31:55is that lutetium can also emit.
31:59Image trace that you can see on camera
32:02on gamma camera and you can basically
32:05see exactly where lutetium dotatate went.
32:08Now it's not as crisp
32:10and beautiful as pet CT,
32:11but you can actually see
32:14where this therapy went.
32:16And you can actually start
32:18doing those symmetry.
32:20These images so this kind of technology
32:24allows selection of right patient
32:26and providing the right drug for
32:29the patient and in neuroendocrine
32:31tumors that has really changed how
32:34we change how we treat patients.
32:36So the indications for lutetium dotatate.
32:41So these are the GI neuroendocrine tumors
32:44and they have to be well differentiated.
32:47G1 and G2 tumors.
32:49We need to confirm some metastatic
32:51receptor expression and that can be
32:54done with gallium dotatate PET CT.
32:57We're still allowed to use octreoscan
32:59and sometimes we will use it if
33:01insurance will deny that the pet city,
33:03but you really want to be
33:05doing this with a pet CT.
33:07We also evaluate bone marrow function,
33:09renal function, and liver function.
33:11Yes, and this is the point where nuclear
33:15medicine physicians are starting to
33:18become partners with oncologists and
33:20surgeons in treatment of these patients.
33:23Because we no longer just read the
33:25images were actually evaluated.
33:26Whether the patient is eligible
33:28for the study and we evaluate,
33:30follow up, and we do those symmetry.
33:33And this is of patient oriented,
33:36patient facing role for nuclear
33:39medicine physicians and radiologists.
33:42Now.
33:44Even though the letter one has
33:46established the parameters for
33:48treatment of patients with Sarah,
33:51but we are still,
33:53we're still figuring out the exact
33:56guidelines for which patients will
33:58benefit most, and they're still.
34:00There's a lot of active research
34:02going on in this field,
34:03and it's very exciting to be part of
34:05this field as we're expanding beyond
34:08the netter one. Trial indications.
34:12But you're probably thinking,
34:14well, what about FDG?
34:16GS News and pretty much every
34:19other oncological indication.
34:21How about your endocrine tumors?
34:23Well, a lot of the well differentiated
34:28G1 on your endocrine tumors are
34:30actually not hypermetabolic,
34:31so we there's really no no role
34:33for our DG in the in the well in
34:36the well differentiated once,
34:38and there is the spectrum
34:40that the tumors will express.
34:44A lot of this medicine receptor
34:46and will not have as much.
34:48Hypermetabolic activity,
34:49but the higher grade tumors.
34:52Then you're in different parts.
34:53Sonoma is Angie 3 tumors.
34:56They will have hypermetabolic
34:59activity and there's still a lot of
35:02Gray area in between them as well,
35:03because sometimes they look the
35:05lower grade tumors will also
35:07have hypermetabolic activity,
35:09but in nuclear medicine we
35:11have this idea that there's
35:12dedifferentiation that happens.
35:14So this is a patient with a
35:16well differentiated neuron,
35:17different tumor.
35:18With multiple somatostatin receptor
35:20avid lesions and this is a patient
35:24that had dedifferentiation that
35:25neural different from which the
35:28tumor is now hypermetabolic,
35:29and this tumor may actually be a
35:32photo piknic Ondo Dotate pet as well,
35:35or it can actually expect express
35:37sounds of medicine receptors,
35:38but not as many.
35:40So the exact point where we
35:42would treat these patients,
35:44particularly the ones that have FDG uptake.
35:48Is still not fully evaluated,
35:50but hypermetabolic activity
35:52within these tumors is seen as
35:55a poor prognostic marker.
35:57So in terms of PRT treatment,
36:01the details for this treatment
36:02is we do right now.
36:04Standard dose of 200 millicuries
36:06every eight weeks and we do 8 cycles.
36:10During the therapy we do an amino
36:13acid infusion for renal protection
36:15and we provide antiemetics for nausea
36:20and patients usually will continue
36:22somatostatin and lock therapy at
36:24this during PRT treatment now.
36:26None of you are thinking well. What if?
36:30How do how do we treat a patient?
36:34Every single patient with the same dose?
36:37And you're thinking right,
36:39the whole field of theranostics right
36:43now and treatment PRT treatment
36:45is moving towards personalized
36:47of symmetry and that is becoming
36:51a big talking point with Society
36:53of nuclear medicine and molecular
36:56imaging and major initiatives.
36:58Industry are being taken.
37:02And the reason is there,
37:04nastix agents are becoming more and
37:07more available for different cancers
37:10and in prostate cancer will have a
37:13new theranostic agent that's very
37:15likely to be FDA approved next month.
37:19And with that targeted therapy,
37:21you want to think about it in a couple
37:23different ways and just in terms of
37:25global way with with their Gnostics,
37:27you can image the targets such as
37:29location of the tumors and that way
37:32you can provide targeted therapy
37:34in terms of location of the tumor,
37:36because you can see where the drug
37:38is and then you can just exchange the
37:41radionuclide and and target that therapy.
37:43You can also think of targeted therapy
37:45in another way where you target as
37:47particular step in the mechanism of.
37:49Therapy, and that is targeting
37:53a specific pathway step.
37:55So for FDA approved radiopharmaceuticals
37:58there's really been an explosion
38:02in the recent years.
38:03So it we really kind of started with
38:06a cold see lemon cooling for prostate
38:10cancer and gallium dotatate was
38:12approved when you're entering tumors
38:14in 2016 and then was followed by
38:17Gallium Delta talk and the difference
38:19between Tate and talk is in the peptide
38:22portion of the targeting agent.
38:25And in there they work pretty much
38:28the same in terms of ability to
38:31detect some metastatic receptors.
38:33We also now have a copper 64
38:37labeled DOTATATE and.
38:40The therapy for lutetium builder did was.
38:44He has also been FDA approved for
38:46quite a while now and it was basically
38:48approved based on the meter one trial,
38:51which showed improved progression
38:53free survival in these patients and I
38:57really appreciate Doctor Koontz going over.
39:00For this so for future directions we
39:04have to evaluate PRT efficacy and
39:08higher grade neuroendocrine neoplasms.
39:10We're also working on personalized symmetry,
39:14so providing the right dose to the
39:17patient and hopefully see better
39:19outcomes in patients,
39:21and we need to evaluate indications
39:23for re treatment of patients.
39:26So after they completed the four
39:28cycles of therapy,
39:29what are the indications for repeat?
39:31Treatment another cycle of therapy
39:34and also of the alpha therapeutics.
39:37And another thing that we're working
39:40on here at Yale is personalized tumor
39:43directed analysis with basically doing
39:49volumetric assessment of the different
39:51metastases and generating growth
39:54curves for each individual lesion in
39:58the in volumetric form and following.
40:01Physical growth parks and figuring out
40:04which lesions are growing and needs
40:07targeted therapy through different
40:09ways and which ones are not so, so.
40:15In conclusion,
40:15cross sectional imaging with CT and
40:18MRI can can diagnose and follow
40:20in your Endocrine meal Plaza.
40:23And it's they're really excellent ways
40:27to do imaging for these patients, but.
40:31And molecular imaging of somatostatin
40:34receptor expression allows for better
40:37molecular characterization of new rendering.
40:40Neil plasm's.
40:41Gallium Dotatate pet is very sensitive
40:44for detection of metastatic lesions
40:47and allows to evaluate whether patient
40:50is is eligible for PRT lutetium
40:53dotatate therapy is established
40:55and allows to treat some medicine
40:59and receptor tumors expressing
41:01some extra.
41:04Staten receptor expressing neuron doctrine,
41:06neoplasms, and it allows us to
41:09visualize the location of the therapy
41:12and many advances for personalized
41:13therapy are being evaluated right now,
41:16so stay tuned to this field 'cause
41:18it's really changing how we're
41:20managing their endocrine schermers.
41:22I really want to thank you for your time
41:26and pass the Bhutan to doctor Sajid Khan.
41:41You're on mute. Doctor Khan.
41:57OK, OK, I think I'm unmuted now.
42:00I'm is that right?
42:02OK, yes, OK, alright.
42:04Thank you Doctor rebellion that
42:06was just an outstanding talk.
42:08I learned a lot from that talk and I'm sure
42:10other people in the audience learned a lot.
42:12And Doctor Kunz talk was also at standing.
42:16So, uh, you know, so I'm going to
42:18spend the next 20 minutes talking to
42:20you from a slightly different perspective,
42:22and one that will include the surgical
42:26management of neuroendocrine tumors.
42:27And since just the surgical management
42:30of neuroendocrine tumors is a
42:32large topic in and of itself,
42:35no, over the next 20 minutes,
42:37I'll focus specifically on
42:38pancreas and small bowel,
42:39new render consumers and and I'd love to
42:43ask answer any questions towards the end.
42:46First time I have no disclosures.
42:50So this is a a slide from a paper that
42:54Doctor Kuhn said side didn't hurt talk for.
42:57Looking at it from the
42:59end where they looked at.
43:02Sear based study of the incidence of
43:05neuroendocrine tumors over the course of
43:08time and what's striking about this talk,
43:11and this is kind of the punch line.
43:13One of the points that Romans made
43:15is neuroendocrine tumors are not
43:16necessarily a rare anymore because
43:18the incidence of these is rising and
43:21this includes the focus of this talk,
43:24which will include pancreas
43:25neuroendocrine tumors and as you can see,
43:27there's been a very steady and
43:29then more recently,
43:30a steeper rise in the incidence of pancreas.
43:33Under consumers and in green over here,
43:36a small bowel or under consumers.
43:382 and that'll be the focus of this talk.
43:41I'm sure many people in
43:42the audience know that.
43:44Many of our patients are getting scans.
43:46A cross sectional imaging,
43:48and they're often incidental findings.
43:51And oftentimes these are how
43:53neuroendocrine tumors are discovered
43:54as our other kinds of tumors as well,
43:57and I'm sure that's driving the higher
44:00incidence that that we're seeing over time.
44:03So the interesting thing about
44:05neuroendocrine tumors is that the
44:07survival for neuroendocrine tumors is,
44:10generally speaking,
44:10favorable when we and the focus
44:12again will be on pancreas.
44:14Neuroendocrine tumors and small
44:16bowel neuroendocrine tumors and
44:18the survival is dependent on grade,
44:22and we're not going to talk too
44:24much about grade three grade 4 door
44:26under consumers and much of what
44:28we see are grade one and grade tuna
44:31under consumers and the survival.
44:33Is is usually favorable and that leads to.
44:38That the perspective of how these new
44:40entrants should be managed and you know,
44:43and you know I'm going to give you my
44:46perspective as a surgical oncologist.
44:48And I think we all have our
44:49own perspectives on things.
44:50And as a surgical oncologist at
44:53longer progression free survivals,
44:55the longer survivals impact how?
44:57What kind of surgical management
44:58we offer to our patients.
45:02So for the talk, we'll break it up
45:04into the remainder of the talk.
45:05Will break it up into three different.
45:08Sessions one will be the pink
45:10richner endocrine tumors,
45:11which I'll talk about first.
45:13I'll follow that with the small
45:15bowel and are under consumers.
45:16And lastly, we talk about metastatic
45:19neuroendocrine tumors as well.
45:21These are common surgical scenarios
45:23that maybe some of your patients
45:26have experienced and and hopefully
45:29this will provide some types.
45:32So in regards to the pancreas
45:35narender consumers.
45:36So you know,
45:36I think in order to understand
45:38if someone needs an operation,
45:40one needs to just understand the
45:41basics of the neuroendocrine tumors.
45:43And you know these are some of the points
45:44that are important to a surgical oncologist.
45:46When we see patients who think
45:48christner under consumers.
45:49I'm I'm very interested in tumor
45:51biology and I could tell that to
45:53rebooting is also from her very
45:54elaborate talk and pink Krishna
45:56render from rumors arise from the
45:58endocrine cells of the pancreas,
46:00which are important to understand
46:03and they account for 3% of
46:06pancreas tumors altogether.
46:08So still pancreatic ductal
46:10adenocarcinomas and other kinds
46:12of tumors comprise majority but 3%
46:15of pink christner under consumers
46:17are comprised of by peanuts.
46:19The median age at diagnosis is 60
46:22years and the survival is longer
46:24than that anchors adenocarcinoma,
46:26so that's very important point
46:28to understand is as all of us
46:30in the audience have.
46:31I'm sure I can understand,
46:33and they're obviously people.
46:35Some celebrities over the years that
46:38we have observed that have been
46:39diagnosed with these kinds of tumors.
46:41Both adenocarcinoma.
46:42I think Christina render consumers.
46:45The note status is very important,
46:47so patients with node negative
46:50peanuts tend to
46:51have them. Sorry to interrupt you,
46:53your slide is not projecting it maybe.
46:57Yep, there you go. Perfect, thanks.
47:01Sorry, so the survival is very
47:03important based on the nodal status.
47:05So patients with no negative peanuts have
47:09a very favorable survival at 136 months.
47:12The addition of noteworthy metastasis
47:15to lymph nodes decreases at survival
47:18to 77 months and one patient
47:21present with distant metastases.
47:23This survival is 24 months and
47:26you know that's important to
47:28understand because 60% of patients
47:30do present with distant metastases.
47:32And I think that plays into
47:34the decision making process.
47:35So for how to treat the patient
47:38to optimally and as doctor Kunz
47:40had mentioned during her talk,
47:41majority of cases are sporadic
47:43and some are familiar.
47:48Pink Reisner under consumers are
47:50nonfunctioning tumors and and
47:52functioning tumors and and by this what
47:55I mean is that nonfunctioning tumors
47:57do not produce clinical symptoms,
48:00even though the tumors can't
48:01still produce hormones,
48:02but they don't produce enough
48:04hormones that cause clinical symptoms.
48:05The nonfunctioning tumors,
48:08now in the updated literature,
48:11revealed account for about
48:1375% of these tumors.
48:14I think some of this has to do with
48:15these smaller new render consumers,
48:17the child.
48:17Talk a little bit about that are
48:19diagnosed more and more frequently
48:21in that number has increased over
48:24overtime and then functioning tumors,
48:26so functioning tumors are tumors
48:27that have hormone hypersecretion that
48:29does lead to clinical manifestation.
48:32The six types are listed here,
48:34which are insulinomas most
48:35commonly that we see Glucagon,
48:37omas,
48:38gastrinomas VIP,
48:39omas Mathis adenomas and others
48:41as well functioning tumors tend
48:43to have better survival than
48:46nonfunctioning tumors and part of this.
48:48Probably is patient present symptom
48:49with symptomatology earlier than
48:51non functioning tumors and that
48:52might lead to a better survival
48:54ultimately because it was diagnosed
48:56or earlier on in the process.
49:00So when a surgical oncologist,
49:02if you come to Yale Surgical and
49:03I see one of the Yale surgical
49:05oncologists you know there are
49:07certain things that we think are
49:08important to to guide our principles
49:10of of sort of surgical management of
49:12patients for assessing a patient.
49:14For that and our goals for surgery are
49:16the first is to maximize local control,
49:19so I think that's a very important point
49:20for not just bankers neuroendocrine tumors,
49:22but in general for other types
49:25of neuroendocrine tumors as well.
49:27Another goal is to increase ones.
49:29Quality of Life OK,
49:30so sometimes that even non functioning
49:32tumors can have an adverse effect
49:33on the individuals quality of life.
49:35So surgery can improve, increase funds,
49:38quality of life progression.
49:40Free survival is an important point
49:42as well too given the the the the
49:44behavior of these tumors a lot of times
49:47we focus on progression free survival
49:49and not as much as overall survival.
49:52So progression free survival is very
49:53important for this kind of tumor.
49:55Generally speaking we aim for
49:57R0 resection margins and that's
49:59something we strive for for many.
50:01Kinds of search conchology
50:03operations and that just simply means
50:05microscopically and grossly negative.
50:07We'll talk a little bit more about.
50:08There's some different that's
50:09not always the case,
50:10but that's for some of the metastatic tumors.
50:12But we are usually striving for
50:15an artist or section and the other
50:17final goal is we try to alleviate
50:18clinical symptoms,
50:19and this is very important for those
50:21with the functioning or underprint tumors.
50:23And and with the source of the hormone,
50:26hypersecretion is removed.
50:27It can substantially alleviate ones
50:30clinical symptoms in the completely.
50:32Address it altogether.
50:34And we also, you know,
50:35with our surgeries and a lot of
50:38these pancreas cases can be major
50:40operations and us.
50:41But we do try to limit our short
50:44term morbidity and the long term
50:46morbidity as well too in the few.
50:48See one of the surgical oncologists at Yale.
50:50We our role is taking this
50:52into consideration.
50:55So, so I'm gonna give you some
50:58specific surgical scenarios here
50:59that may be of some use and you know
51:02one scenario includes a patient that
51:04presents the localized non metastatic
51:06pancreas neuroendocrine tumor.
51:08And generally speaking,
51:09we respect the for the resection is feasible.
51:11The meeting survival in the
51:15literature is 7.1 years,
51:17but the important thing to understand,
51:19and is that about half the patients
51:22do recur at two almost three years.
51:25So recurrence free survival is
51:27important to consider here as well,
51:29so so many patients to recur.
51:34Another common scenario are these small
51:36pink trees that are under 15 years,
51:38so these are pink creature under
51:39consumers that when we when
51:41we say that there are small,
51:42we're thinking 1.5 to 2 centimeters in the
51:45depends on which studies you're looking at.
51:47There's a good study out of
51:48the University of Chicago.
51:49There's another good study out of
51:51Massachusetts General and then that's
51:53where this number of less than two
51:55centimeters or 1.5 to 2 centimeters comes up,
51:58because given the behavior
52:00of neuroendocrine pancreas,
52:01neuroendocrine tumors in general.
52:03Sometimes surgery is not
52:05necessary for these patients,
52:07but I would recommend careful
52:11observation and you know each patient
52:14is an individual and we need to every
52:17patient should be evaluated individually
52:19and and but oftentimes patients with
52:22smaller tumors can be observed,
52:25you know, and I just want to make
52:26a quick comment about that.
52:27And that being said,
52:28you know if there's a young
52:29patient that's diagnosed with.
52:30They say, for example,
52:321.8 centimeter neuroendocrine
52:33tumor that's in.
52:35Yeah,
52:35in her late 20s or so,
52:38you know one can make a reasonable argument
52:40that with a longer life term expectancy,
52:42maybe that might not be the person we tried.
52:44Decide to observe with the small neuron
52:46consumer and we do survey these patients.
52:48And if there are changes to
52:50their cross sectional imaging,
52:51which is an important point
52:53for neuroendocrine tumors,
52:54we will consider them per section.
52:58Another scenario that sometimes
52:59comes up is a locally advanced and
53:01metastatic on fund, resectable.
53:05Patient in that kind of a scenario,
53:07you know, sometimes we consider
53:09palliative surgery with some
53:11of the options listed here,
53:13and that's sometimes a scenario
53:15and then limited liver metastases.
53:18We're going to talk at the last
53:19third of this talk a little bit more
53:22about metastatic disease and in some
53:24patients with limited liver metastases.
53:26Will will use a asynchronous approach
53:28where the primary tumors are addressed
53:30and the liver tumors is addressed,
53:32or we considered a surgery in a staged.
53:35Fashion.
53:37So for all of these for sections I'm
53:40I just figured I'd share some patient
53:43examples for you to try to put it
53:46into some perspective and and the
53:48first patient I'd like to present is
53:51an 80 year old male who presented
53:54with hypoglycemic episodes and he had
53:56what's called the Whipple's triad,
53:58which we've heard about,
54:00and for Pinkerton are under consumers,
54:03what we teach our residents is, you know,
54:05if if you're ones considering a functional.
54:08Increased our hundred tumor work up
54:09starts with the biochemical workup and
54:11this patient did have a biochemical
54:13work work up,
54:14which indeed was consistent with insulinoma.
54:17After the biochemical work up,
54:18then we preceded with the localization
54:20studies to identify where this tumor
54:23is located and and in this patient.
54:25Here, this is the the frontal
54:28images and and it shows.
54:30I don't think my arrow is projecting here,
54:32but there's a hyper enhancing mass in
54:36the head of the pancreas which is seen.
54:39And that is sometimes the look
54:40of how a neuron tumor shows
54:42up on cross sectional imaging,
54:44and we performed a pancreaticoduodenectomy
54:47with an extended lymphadenectomy on this
54:50patient specimen seen on the right,
54:52and interestingly,
54:53immediately the patients hypoglycemic
54:55episodes were completely resolved and
54:58provided this gentleman with many,
55:00many years of custom free life.
55:06Next, I'd like to transition to
55:09small bowel neuroendocrine tumors.
55:11And these are tumors that are
55:14submucosal neoplasms which primarily
55:16arise from the jejunum and the ileum.
55:18And there they do have
55:20neuroendocrine differentiation,
55:21just like some of these other tumors
55:23that we're talking about today.
55:25They have an ability to secrete
55:28functional hormones and a means they
55:30are the most common tumor of the
55:32small bowel with malignant potential.
55:34Which is interesting because this is
55:36shifted because when I was in intern
55:39almost 20 years ago now we used to not
55:42look at small bowel neuronal tumors as
55:45the most common small bowel tumors.
55:47We would think more of adenocarcinoma
55:49and then more often even benign tumors.
55:51But interestingly,
55:52now neuroendocrine small bowel
55:54tumors are the most common.
55:56Small bowel tumor with Fullington potential.
56:00Nearly a third of these tumors arise
56:02relatively close to the ileocecal valve,
56:05and that the reason that's important
56:07is our operative decision making
56:09takes that into consideration.
56:11Many patients present with multifocal
56:13disease that's also very important.
56:15When I talk about surgical approaches,
56:18and about 35% of patients
56:21present with distant metastases,
56:23so surgical resection is a preferred
56:25frontline treatment for these patients.
56:29And the reasons for that is number one.
56:31It can improve survival.
56:33Number two can reduce the risk
56:36for developing metastatic disease.
56:38#3 can alleviate symptoms and
56:41finally #4 it can prevent or delay
56:43the onset of symptom development,
56:44and that's important as we
56:46talk a little bit more here.
56:49So you know.
56:49So like I thought it would be
56:51useful to go over some scenarios
56:52that some of your patients may
56:54present with into the hospital.
56:55And 11 scenario is in east symptomatic
56:59prime patient that the patient presents
57:01with asymptomatic disease with the
57:04primary tumor without distant metastases.
57:06So even though these patients
57:08present with asymptomatic disease,
57:10in retrospect,
57:11many of them will have some symptomatology.
57:15And they won't know about it until
57:17after they've had their surgery.
57:19But that symptomatology may have prompted
57:21their imaging in the 1st place and
57:23the cross sectional imaging Dr Booing
57:25can speak to this better than I can,
57:27but oftentimes it shows something such
57:29as a mesenteric or small bowel mass,
57:32which is hyper enhancing.
57:34Speculated or calcified,
57:36and interestingly in the operating room,
57:38you know,
57:39the speculation is something we
57:41really appreciate because these
57:43tumors in the OR or the mesenteric
57:44mass in the OR tend to be fixed,
57:46fixated posteriorly,
57:47as opposed to something that
57:50some freely movable,
57:52which is the case with some of
57:54the benign small bowel tumors
57:55and even small biologists.
57:57Another scenario is an asymptomatic
57:59primary tumor with distant metastasis.
58:02I'm going to talk a little bit
58:04about about that.
58:04In the last scenario,
58:05because I think that's going to
58:07be an important thing to go over.
58:10And and and symptomatically.
58:12You know, sometimes these neuroendocrine
58:14tumors present with the bowel obstruction,
58:17abdominal pain, bleeding,
58:18and the and the so-called
58:21carcinoid syndrome as well so.
58:25An approach that is important is
58:27expectations for our patients suffer.
58:29Patient knows what to expect in a non
58:31emergent setting prior to undergoing
58:33a surgical and conchological section.
58:35It goes along way for their
58:37satisfaction down the road.
58:38That's something that our
58:40our group at Yale uses.
58:42So we talked to our patients ahead of
58:46surgery and one thing that we talked
58:48to our patients about is sometimes that
58:50because of the multifocality of these tumors,
58:53larger areas of small bowel
58:54need to be respected.
58:55Lead to increased frequency of
58:58their bowels of bowel movements.
59:00We also consider perceptibility.
59:01A lot of it comes down to the mesenteric
59:04artery and the vein superior mesenteric,
59:06artery and vein.
59:07That's something we strongly consider for
59:10respectability for these guys into tumors,
59:12we and the surgery usually entails,
59:15and indirectly or small bowel
59:17resection with a lymphadenectomy.
59:18Sometimes it involves resection
59:20of a mesenteric mass,
59:22which is how a patient may present,
59:24and in the operating room.
59:26It's very important to palpate
59:29for synchronous tumors,
59:30so so open operations are preferred
59:32and I just want to spend just a
59:35minute talking about that as well too.
59:37So we do a lot of laparoscopic and
59:40minimally invasive surgery at at Yale.
59:42A lot of our operations are done
59:44in that manner,
59:45and the way I look at laparoscopy
59:47and minimally invasive surgeries
59:48that it should be a tool to provide
59:51a good oncologic operation.
59:53It shouldn't not be the other way around,
59:55meaning someone should not get.
59:56A minimally invasive surgery just
59:58for the sake of getting minimally
60:00invasive surgery,
01:00:01but so so for the way we approach
01:00:03these are we usually will do them.
01:00:05Laparoscopic Lee roulette,
01:00:06metastases and sometimes we could
01:00:08make a very small incision and
01:00:10eviscerate the tumor and palpate
01:00:12the entire small bowel to make
01:00:14sure that they're synchronous.
01:00:15Tumors are are not missed,
01:00:16which sometimes is the case with
01:00:18true laparoscopic operations.
01:00:19For these small bell,
01:00:21any tease we value for distant
01:00:24metastases and sometimes consider a
01:00:26cholecystectomy and a lot of that.
01:00:27Ends up being a conversation with the
01:00:30surgical oncologist and medical oncologist,
01:00:32and about this patient may be a
01:00:34candidate for lanreotide in the
01:00:36future which can predispose to the
01:00:38development of gallstones. Uhm?
01:00:41So so a few scenarios.
01:00:43So patient presents with an incidental
01:00:46finding on cross sectional imaging.
01:00:48You know our suggestions are the
01:00:50patient should be evaluated by a
01:00:52surgical oncologist per section
01:00:53the patient presents,
01:00:55with an isolated mesenteric
01:00:57mass or small bowel mass,
01:00:59and the reasons we consider surgery
01:01:01are again, it could be diagnostic.
01:01:03Sometimes these tumors are not
01:01:04always new render consumers,
01:01:06but they usually are when we look
01:01:07at it with our radiologists,
01:01:09but sometimes they're not,
01:01:10so it's something to consider.
01:01:12In,
01:01:12the operation is potentially curative
01:01:14and this is very important.
01:01:16It can avoid future symptoms
01:01:18of bowel obstruction,
01:01:19bleeding or ischaemia,
01:01:20which sometimes happens in these
01:01:22small bells are under primary.
01:01:23Tumors are left alone,
01:01:25so that's an important point to
01:01:27mention and we and we do see
01:01:28that sometime and again with the
01:01:30patient that had an arrangement
01:01:32in which was being observed and
01:01:34so and the patient can present
01:01:36with some symptoms down the road.
01:01:39And of course it can avoid reduced risk.
01:01:41For tests.
01:01:44Another scenario is an asymptomatic
01:01:46primary with distant metastasis,
01:01:47and again this can be.
01:01:50This would suggest to be evaluated
01:01:52by a surgical oncologist and and
01:01:54the reasons for surgery in order
01:01:56to avoid future complications and
01:01:59metastasis and and discomfort.
01:02:02This kind of an approach can
01:02:03still provide a profession free
01:02:04survival advantage.
01:02:08And then and then, if patients.
01:02:10Sometimes patients present symptomatically
01:02:12and impatient that's presenting
01:02:14symptomatically should probably just get
01:02:15to the operating room and be seen by a
01:02:18general surgeon in the local hospital.
01:02:19Because sometimes these patients you
01:02:21know don't have room to be transferred,
01:02:23and they and acute ballot traction
01:02:25should just usually be managed
01:02:27locally and the reasons for this.
01:02:29Of course the obvious it
01:02:31alleviates her symptoms.
01:02:32That it can be diagnosed
01:02:34and be potentially cured.
01:02:36And a patient example here is an
01:02:39asymptomatic patient patient with
01:02:41an asymptomatic small bell NET.
01:02:43This is a 59 year old male who presented
01:02:45with a 4.2 centimeter hyper enhancing
01:02:47mesenteric mass on CT for abdominal pain,
01:02:50which resolved by the time we evaluated
01:02:54him and then this picture shows a CAT scan
01:02:57with a hyper In Sync 4.2 centimeter mass,
01:03:00which we ended up taking to
01:03:02the OR and resecting which is
01:03:04showing all the way in the right.
01:03:06And we did an enbloc small bowel
01:03:09resection with the mesenteric mass
01:03:11and the and the surgical pathology
01:03:14revealed multifocal tumors.
01:03:16Node positive disease without metastasis,
01:03:19and it was a grade one tear.
01:03:22And finally,
01:03:23I'll end this session by submitting
01:03:25metastatic here under consumers.
01:03:27So again,
01:03:28some perspective on things from
01:03:30a surgeon's perspective that so
01:03:31the reason we find this important
01:03:33is because the third patient,
01:03:34present with cysteine metastasis
01:03:36in the liver,
01:03:37happens to be the most common
01:03:39site of metastasis.
01:03:40Metastasis is important because
01:03:42it negatively affects revival as,
01:03:44as we know,
01:03:45and that's the case with all cancers,
01:03:47and there's a increased risk of
01:03:49death compared to an individual
01:03:51that has localized disease.
01:03:53Clinical presentation can
01:03:54include hormonal symptoms,
01:03:56and that's more often the case
01:03:57for small bowel and any tease.
01:03:59This could be diarrhea,
01:04:01wheezing and flushing,
01:04:03and sometimes the patients could
01:04:05have valves are right sided valvular
01:04:07disease which can lead to heart failure.
01:04:10Increase your under.
01:04:11Consumers are important.
01:04:12They're at their often nonfunctional
01:04:16in cases of metastasis.
01:04:18The goal for the arguments supporting
01:04:21surgery for metastatic any teas
01:04:23are the first in the important
01:04:25thing is to control the tumor
01:04:27burden and by respecting ones
01:04:29metastatic neuroendocrine tumors.
01:04:31The progression free survival improves
01:04:34the patients as a whole and you know
01:04:38the literature can show five year
01:04:40overall five year survival up to 74%.
01:04:42That's overall survival,
01:04:43but the important thing to understand
01:04:45is there's a high risk of recurrence.
01:04:47Despite that kind of an approach,
01:04:49so even though I'm talking
01:04:50about 5 year old roll survival,
01:04:52if 74% the recurrence rate
01:04:54is nearly is over 80%.
01:04:57But there is benefit to doing
01:04:58this because it can provide
01:04:59effective symptom control,
01:05:00particularly for functioning tumors.
01:05:01It could prevent or delay the
01:05:04sequelae of carcinoid syndromes.
01:05:05It can improve one's performance
01:05:07status and pain,
01:05:09and this is the case more for
01:05:12nonfunctioning tumors and the number
01:05:13has shifted us to the number of the
01:05:15percent of tumor that we'd like to site,
01:05:17or reducing individual.
01:05:17And there was a time where.
01:05:19We used to think more along the
01:05:21lines of 90% but more recent
01:05:23literature has suggested that that
01:05:25number might be closer to 70%.
01:05:27Reduction of the tumor burden,
01:05:29and it's important if one can
01:05:30have this kind of cytoreduction,
01:05:32and we usually try to remove the
01:05:34primary tumor in the regional disease
01:05:36in this 70% number that I mentioned.
01:05:38But even if one does not have their
01:05:41primary tumor that's identified.
01:05:42One can still consider a cytoreductive
01:05:44surgery if greater than 70% of the
01:05:47disease burden that's clinically
01:05:49present can be addressed.
01:05:50And extrahepatic disease is not a
01:05:52contraindication to the surgical
01:05:54site or reduction.
01:05:57The tools that we use in surgical
01:06:00oncology for Cytoreduction,
01:06:01and I'm focusing a little bit more
01:06:02on the liver because I'm very
01:06:03biased towards the liver and, uh,
01:06:05I like operating the liver and then
01:06:06this ends up being the most one
01:06:08of the most common sites for the
01:06:09most common cited medicine disease.
01:06:11For any tease, we often will try to do
01:06:13what's called prank while sparing resections,
01:06:15because, as I mentioned before,
01:06:17many of these patients were occur and
01:06:20and they can have a longer survival,
01:06:23and they can recur in the liver,
01:06:24so we try to do prank whispering resections.
01:06:26Impossible understanding that.
01:06:27Well, if there's another recurrence
01:06:29down the road,
01:06:31it can allow the patient for a
01:06:33second liver operation or liver
01:06:35directed therapy down the road.
01:06:36But sometimes we do need to perform
01:06:39major head protect me as given the
01:06:41distribution of the testis is sometimes
01:06:43we consider a microwave ablation where
01:06:46we put a probe into the center of the
01:06:48tumor or sometimes our interventional
01:06:50radiology colleagues who are very
01:06:52adept at doing that can do that as well too.
01:06:54And if they can do it in
01:06:56the last invasive fashion,
01:06:57that's always.
01:06:57Investing for the patient and surgical
01:07:00site or rejection should be attempted
01:07:02when it's anatomically feasible and it
01:07:04can be performed with a low morbidity.
01:07:07So I'll end with a patient example,
01:07:10and this is a 62 year old male who,
01:07:12when I had seen him,
01:07:14was five years after the status posted,
01:07:16dissipate protect me for nonfunctioning
01:07:18tankers or under consumer one of his smile.
01:07:22Medical oncologists was surveying
01:07:23him and and identified enlarge.
01:07:26Enlarge incompat exclusions on
01:07:28surveillance cross sectional images.
01:07:31And this doesn't show everything,
01:07:32but this is a patient that had three
01:07:35tumors when we had seen seen him,
01:07:37one in the left lateral liver,
01:07:39one in the left medial liver,
01:07:41and then one in the right liver.
01:07:42And and then we went ahead and we
01:07:45actually needed to do a a major
01:07:47liver section for the left side,
01:07:49and apparently sparing resection on the
01:07:51right side to clear all of the disease.
01:07:54And and we did a cholecystectomy
01:07:56in this case as well too,
01:07:59and the pathology revealed
01:08:01for neuroendocrine tumors,
01:08:02which were identified in the liver,
01:08:04which were well differentiated.
01:08:09So the surgical manager of papers at
01:08:11small bowel neuroendocrine tumors,
01:08:12the incidence is rising.
01:08:15Section of primary neuroendocrine tumors.
01:08:17This clinical benefit and we've shown that,
01:08:20and I've shown that the pancreas for
01:08:22under consumers those non functioning,
01:08:23functioning and for small Val
01:08:25any teas and finally surgical
01:08:27site of reduction for metastatic.
01:08:29Any tease has clinical benefit at
01:08:31greater than 70% of the tumor burden.
01:08:34Which percentage.
01:08:34OK, thank you for your time.
01:08:42Thank you to doctors appointment and con.
01:08:44Those were both great presentations,
01:08:47so I think what we'll try to do is
01:08:49tackle some of the questions that
01:08:51have come through the chat and I also
01:08:53have some questions for the two of
01:08:55you and we can have a conversation.
01:08:56So one of the the first questions
01:09:01that came through is I think this
01:09:03was in reference and Doctor Boy
01:09:04and maybe I'll direct this to you.
01:09:06Is can the Ludo dictate treatment?
01:09:12PRT if it started early I'm
01:09:16can we achieve cure from this?
01:09:20And particularly if the cancer load is low,
01:09:23that's I think aspirational,
01:09:25but I will allow you to maybe
01:09:27comment some on that.
01:09:29What are the goals of treatment and in
01:09:30what setting do we typically use it?
01:09:33Yeah, this is a really great question now.
01:09:38The indications for which PRT is
01:09:41being used for right now is for.
01:09:44For well differentiated tumors,
01:09:46and when we do the therapy majority of the
01:09:50tumors actually do not decrease in size,
01:09:55but it does slow their growth,
01:09:57so there's significant improvement
01:09:59in progression. Free survival.
01:10:01So no, this is not a cure,
01:10:04but it does improve symptoms and
01:10:07improve survival. In patients.
01:10:11So that's for the lutetium.
01:10:14We still have a lot of other therapies in in
01:10:18the pipeline that we're still evaluating,
01:10:20but the goal is not cure.
01:10:22The goal is extension of life
01:10:24and improvement of symptoms.
01:10:27Thank you, there was another question that
01:10:30I think perhaps Doctor Khan can answer.
01:10:32So and I think you addressed this
01:10:35a little bit in the course of your
01:10:37presentation such so is it possible
01:10:39that we maybe can't find the primary,
01:10:42but we do see metastatic disease.
01:10:45You touched on that a little bit in the
01:10:47course of your surgical indications,
01:10:49but maybe you can address that some. Yes,
01:10:51yeah, so that's not an uncommon scenario.
01:10:54Back spoons, and that's very good question.
01:10:57And you know it is all worth it to look
01:11:00for the primary tumor and do a thorough
01:11:03exhaustive look for the primary tumor.
01:11:05However, the primary tumor cannot be found.
01:11:08There is benefit towards some.
01:11:10If a patient has a resectable
01:11:12metastatic disease,
01:11:13which could be said or reduced to over 70%,
01:11:16and the morbidity is is not very high.
01:11:21Uh, I would still recommend
01:11:23consideration for surgical cytoreduction
01:11:25because of the improvement in
01:11:26the professional free survival.
01:11:30And I'll just comment this.
01:11:31You know, entity of unknown primaries is
01:11:33certainly something that we come across,
01:11:35although I will say I think that's less
01:11:38in the era of gallium 68 PET scans.
01:11:40I think we are often identifying
01:11:43the primary a little bit more
01:11:45easily with better imaging so,
01:11:47but we do still see that I have a
01:11:50couple of questions actually there.
01:11:51I think there is one more in the Q&amp;A
01:11:53from the audience, so this is something.
01:11:56Maybe I'll tackle first,
01:11:57but would welcome comments
01:11:58from from my partners.
01:12:00Here, so some cancers,
01:12:02even lung adenocarcinomas,
01:12:04had endocrine secretion.
01:12:05How can we treat that?
01:12:07I didn't personally spend a lot of time
01:12:09talking about how we treat hormone control,
01:12:11but I think for certainly for many
01:12:15patients with neuroendocrine related
01:12:17hormones secretion we the mainstay is
01:12:20really using somatostatin analogs.
01:12:22First they were approved on the
01:12:24basis of controlling hormones,
01:12:26specifically carcinoid syndrome,
01:12:27which is diarrhea and flushing.
01:12:30They are also indicated in some.
01:12:31Other forms of hormones secretion,
01:12:33including gastrinomas and others.
01:12:38But we also try to PSI to reduce or
01:12:41kind of reduce the bulk of the tumor,
01:12:44either through surgery as Doctor Khan
01:12:47indicated or other systemic treatments
01:12:49that have the ability to shrink the tumor.
01:12:52So cytotoxic chemotherapy can do that.
01:12:55Doctor Khan, I think, spoke about
01:12:56some of the like oblated procedures.
01:12:59We often we didn't talk tonight a
01:13:01lot about liver directed treatments,
01:13:03but I think that when patients
01:13:06have secretion of hormones,
01:13:07we really it's tricky.
01:13:09Because we need to think about
01:13:11both managing the hormones and
01:13:12managing the tumor itself.
01:13:14So doctor,
01:13:14can you have any other comments on that?
01:13:17Yeah, I know, I think those are why you
01:13:20know if if if an individual has a patient.
01:13:23If a if a provider has a patient with,
01:13:25you know neuroendocrine tumor general,
01:13:27but in this specific scenario
01:13:29it's good to have them evaluate
01:13:31in a multidisciplinary fashion.
01:13:32Because surgery.
01:13:33I'm not saying everyone needs surgery
01:13:36and sometimes systemic options are
01:13:39much more effective at controlling
01:13:41these symptoms than surgical options.
01:13:44And and I think that's why you
01:13:45know an active discussion by a
01:13:48multidisciplinary tumor board.
01:13:49Is it is very beneficial for the patient,
01:13:52but you know if if one is able
01:13:54to control you,
01:13:54know a high burden of disease like
01:13:56I threw the number of 70% out there.
01:13:58That's that's for surgical literature.
01:14:00But I don't know if this is true or not,
01:14:02but perhaps that would is true for
01:14:05non-surgical approaches as well too.
01:14:07And I think if we're able to
01:14:08address the source of where the
01:14:10hormones are being separated from,
01:14:11we could probably really provide some
01:14:12good clinical abilities to our patients.
01:14:15Right, right now I agree.
01:14:16Good doctor Brian.
01:14:17I have a question that comes up almost
01:14:20in many of my patient interactions
01:14:23and also when I'm teaching trainees
01:14:25this actually just came up yesterday.
01:14:28How do we interpret SUV on Gallium 68 pet?
01:14:32Should we pay attention to it?
01:14:34Is it different than how
01:14:35we think about FDG pet?
01:14:39Oh yeah, that's a great question.
01:14:41It's a we can give a whole
01:14:43lecture tracer uptake,
01:14:46so I would I would think too.
01:14:50I I do recommend to, so it's a.
01:14:52It's a general unit of Tracer
01:14:55update that's generalized
01:14:56to patient body weight.
01:14:59But the the big issue?
01:15:05Hope we lost Doctor Abovyan there for a
01:15:08moment. So hopefully she will be back.
01:15:09I can text her, we technical issues.
01:15:13Related to the tax, there will be a
01:15:15doctor boy and we lost you for
01:15:17just a minute. Maybe you can
01:15:19repeat the last portion of that.
01:15:22Oh sorry, I was having Internet connectivity
01:15:24issues so so in terms of that SUV is
01:15:27it's a it's a way to measure tracer
01:15:29uptake normalized to patient body weight.
01:15:32And it is a semi quantitative that measure.
01:15:35Now there's a whole field of
01:15:38quantitative pet that requires very
01:15:40complex mathematical modeling.
01:15:41And here at EO.
01:15:43Under the guidance of Doctor Rich Carson,
01:15:46their leader leaders,
01:15:47they go pet center in quantitative PET
01:15:49imaging and we're still trying to figure
01:15:51out how to apply to clinical practice
01:15:53because it's not used in clinical practice.
01:15:55But as UV is kind of a poor man's
01:15:58approach to try to quantitate so
01:16:00it's a semi quantitative measure,
01:16:02but I would really focus on looking
01:16:05at the CVS within a specific tracer.
01:16:08So if you're going to compare
01:16:11SUV values only,
01:16:12compare them between gallium dotate scan.
01:16:15Don't compare them between gallium
01:16:17dotate and don't talk or gallium dotate,
01:16:19and if you're so,
01:16:21if you have a patient that's
01:16:23being imaged with MTG pad,
01:16:24then you can compare the SUV values.
01:16:28But if you're patient change
01:16:30significantly so supposedly lost a
01:16:32lot of weight in between the scans,
01:16:35then you have to be really careful
01:16:37and usually in nuclear medicine
01:16:40when we do the reports,
01:16:42we do mention the numbers
01:16:44'cause everybody wants some.
01:16:45Connotation,
01:16:45but we do try to use language as
01:16:49well because it is it's it is
01:16:52a semi quantitative analysis.
01:16:55Thank you, yeah that's helpful.
01:16:58Doctor Khan I have a question that
01:17:00comes up a lot in tumor board.
01:17:02You know, I think I'd
01:17:04love to hear from you of.
01:17:06Are there situations or or notable
01:17:08situations where you're like?
01:17:10Gosh, I really wish I saw this
01:17:12patient earlier, like when?
01:17:14When should medical oncologists or surgeons
01:17:16in the community be thinking about surgery?
01:17:20When should it be on their radar?
01:17:21I'd say specifically for metastatic disease.
01:17:24OK, you know
01:17:27the first. Maybe I can also answer
01:17:29one about non metastatic disease.
01:17:31Some you know. I think if one identifies
01:17:34a hypervascular mesenteric mass,
01:17:35I would consider that I
01:17:37wouldn't just sit on it.
01:17:39I would consider sending it to
01:17:40one of the surgical oncology,
01:17:41or at least one of the general
01:17:43surgeon to evaluate for for it,
01:17:44because you know,
01:17:45every so often we do see a patient that
01:17:48has had this followed a cross sectional
01:17:51imaging and then presents with you
01:17:53know some sort of a problem with the.
01:17:55Primary small bowel related issue.
01:17:57Whether it's this kimia infarct
01:17:59or balance truction and then it
01:18:01becomes more of an emerging problem.
01:18:03And it's something that I probably
01:18:04could be less of a bigger operation
01:18:07for metastatic disease as well too.
01:18:09So actually,
01:18:10the last patient I presented was being
01:18:13followed for awhile because the the
01:18:17tumors were were visible and I had
01:18:20given a talk on liver metastasis about.
01:18:22You know around that time and
01:18:24then the the individual who.
01:18:26Caring for that patient was didn't
01:18:28realize that surgical options
01:18:29and options for that patient,
01:18:31so I think if a patient is known to
01:18:34have a neuroendocrine tumor and perhaps
01:18:36present was the liver metastases,
01:18:38I think it's worth it for that
01:18:40patient to be seen by GI medical
01:18:42oncologist or surgical oncologist.
01:18:43Because I do think that we can
01:18:47provide a good progression free
01:18:49survival benefit for most patients
01:18:50in that kind of a scenario.
01:18:52If with a good multidisciplinary approach.
01:18:58Great thank you and doctor Brian.
01:19:01Maybe I'll ask you one one more and sort of.
01:19:04I'd say a really exciting direction
01:19:06and something you and I are
01:19:08partnering on is really thinking
01:19:10about a theranostics program.
01:19:12Can you speak to how you think the field
01:19:14is changing and how we are likely to see
01:19:18the development of theranostics programs?
01:19:21Sort of in multiple locations,
01:19:23but maybe the value of that.
01:19:25What that means and and sort of how
01:19:27nuclear medicine docs are going to be.
01:19:29Providing direct patient care.
01:19:32Oh, thank you. Yes,
01:19:33this is a very exciting field and
01:19:35I just came back from Society of
01:19:37Nuclear Medicine and Molecular Imaging
01:19:39Therapeutics conference where we met
01:19:42for several days and talked about
01:19:44how different sites across USA are
01:19:47starting the theranostics centers and
01:19:50their layout plans and how they're
01:19:52going to be treating the patients.
01:19:54And this is really changing
01:19:56radiology and nuclear medicine.
01:19:58We are now going back to senior patients.
01:20:01We're now we're now becoming.
01:20:03Parts of teams with oncologists and
01:20:05surgeons and really practicing together
01:20:08and with radiation oncology as well and
01:20:10we're really practicing together as a
01:20:13team in terms of taking care of patients.
01:20:17There's sites where patient is being
01:20:20seen by their GI oncologist and followed
01:20:23up by a visit with nuclear medicine Doc
01:20:27to discuss PRRT and the specifics of
01:20:30radiation based therapy radionuclide.
01:20:34Therapy and that really helps patients
01:20:37in terms of understanding what
01:20:38they're going to be undergoing and
01:20:41their side effects and the risks.
01:20:43The nuclear medicine physicians
01:20:44are following up on the patients
01:20:46and are involved in in the care.
01:20:48So another thing that's really helpful
01:20:51is that we're starting to combine
01:20:53chemotherapy with radionuclide therapy
01:20:55and trials and trying to see how we can
01:20:59improve the efficacy of these therapies.
01:21:01And the only way to do it
01:21:02is to work together.
01:21:04So it's a really exciting team
01:21:06based approach that's happening
01:21:08across the country and it's it's
01:21:11really gonna change radiology
01:21:12and how we care for our patients.
01:21:17Not very exciting, I think.
01:21:19Lots of opportunities for asking for
01:21:21for both providing really excellent
01:21:23patient care and I think you know
01:21:25one thing we can speak to is really
01:21:28the importance of multidisciplinary
01:21:29care for the care of these patients.
01:21:31I think the intent was to have three
01:21:33different disciplines represented on
01:21:34on this panel tonight and I think
01:21:36we all certainly work together and
01:21:38caring for our patients with Nets.
01:21:41So I think what we can do is
01:21:43I don't see other.
01:21:44I don't know if Doctor Boyd or
01:21:46Doctor Khan you had any other
01:21:47burning questions for each other
01:21:48or anything that has come up.
01:21:53If not, I really want to thank the
01:21:55two of you. Certainly for your time
01:21:58and and excellent presentations,
01:22:00I want to thank our audience for
01:22:02their time and and listing tonight.
01:22:05This will. This has been recorded
01:22:06so we will make this available to
01:22:09the Community and stay tuned for our
01:22:13future GCM E series in April and May.
01:22:16We will promote those and hope
01:22:17that some of you will listen again.
01:22:19So thank you and have a wonderful evening.