Smilow Shares: Understanding NETS

November 10, 2021

Information

November 9, 2021

Presentations By: Drs. Pamela Kunz, John Kunstman, David Madoff, Darko Pucar, and Mariam Aboian

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00:00OK, so I'll go ahead and get
00:01started so welcome everybody.
00:03My name is Pam Kunz.
00:04I am a GI medical oncologist and
00:06I focused on the care of patients
00:09with neuroendocrine tumors and it
00:11is really our pleasure tonight to
00:13do a special patient focused event.
00:16We call them smilow,
00:17shares understanding Nets,
00:19new treatment advances and innovations.
00:23And I have some exciting news,
00:25so this is also timed.
00:26This event is timed with net Cancer
00:29Awareness Day which is tomorrow and
00:31we just got news that Connecticut
00:33has officially acknowledged this
00:36day in the state of Connecticut
00:38as net Cancer Awareness Day and
00:41what's also really exciting.
00:44And this is through advocacy work through
00:46the Carcinoid Cancer Foundation that
00:48the large majority of the United States,
00:51including Puerto Rico has also.
00:53Acknowledged net Cancer Awareness
00:55Day officially on in November 10th.
00:58So I'd like to just briefly
01:00introduce our speakers.
01:01We are going to go in this order,
01:03so I will be speaking first on next 101
01:06and basics of treatment also moderated.
01:08Q&A Doctor Jon Huntsman,
01:10an assistant professor of surgery,
01:12will be speaking about
01:14surgical management of Nets.
01:15Doctor David Madoff,
01:16professor of radiology and
01:18interventional radiology will be
01:20speaking about liver directed treatment.
01:22Dr Darko Poker associate
01:24professor of radiology,
01:26will be talking about imaging of Nets.
01:28And Doctor Miriam,
01:29a boy and an assistant professor
01:31of radiology and nuclear medicine,
01:33will speaking will be speaking
01:35about theranostics and peptide
01:37receptor radionuclide therapy.
01:38So we will start with the basics just
01:40to get everyone on the same page.
01:42In terms of background and nomenclature
01:44and some basics of treatment.
01:47So I'd like to start with a slide that
01:49I think is actually incredibly hopeful.
01:51It is a timeline of development of new
01:55FDA approvals in neuroendocrine tumors,
01:57which are along the.
01:59The bottom part of your screen
02:01and also imaging approvals and
02:02in the last decade we have seen
02:05just an explosion of research in
02:07neuroendocrine tumors and we've had
02:10seven new FDA approvals in a number
02:13of different disease indications.
02:15Pancreatic net long net
02:18Jeannette carcinoid syndrome,
02:20and three new imaging modalities
02:23that have also been approved.
02:25So I'd like to start with
02:26a little bit of history.
02:27I always find this interesting,
02:29so some of you may have heard
02:30of the term carcinoid.
02:32It's actually a German term that
02:34was coined in the early 1900s
02:36by a German pathologist, Dr.
02:38Or burned,
02:38or for whose picture is there on
02:40the right he described this cancer
02:42and meant that it was quote cancer
02:45like I think he contributed a great
02:47deal to the field and really started
02:50some of the research in this area.
02:52But it was a misnomer.
02:54We now in fact know these.
02:55Are cancers and they are coded as
02:57such and treated that way I will and
03:00will speak about more of that later.
03:02Nets can start throughout the
03:04body called the primary site.
03:06That's where they originate,
03:08and they most commonly start in
03:09the GI tract in the lungs.
03:11Nets are rare by incidence,
03:13meaning the number diagnosed per year
03:15but are more common by prevalence,
03:17meaning the number of patients
03:19alive at any given time.
03:20Most grow slowly in comparison with
03:23their adenocarcinoma counterparts.
03:25Adenocarcinomas are the more common type of
03:28GI cancers like the run of the mill, colon,
03:31cancer or run of the mill pancreas cancer.
03:34And somatostatin receptors,
03:36which many of us will touch on,
03:37is is a special receptor on the
03:40surface of neuroendocrine tumor cells,
03:42and they're usually present on
03:44the surface of most net cells.
03:48This is a little bit of a busy table.
03:50I want you to focus along the left.
03:52These are what I consider key patient
03:54characteristics that impact treatment.
03:56We're going to spend a few moments
03:58on on some of these hormone status,
04:00extent and burden of disease.
04:02That's really the stage grade and
04:05differentiation pace of growth.
04:08Primary site and means somatostatin
04:11receptor status.
04:12So let's talk a little bit about hormones.
04:15Some of you may have heard the
04:17terms functional and nonfunctional.
04:18Both functional means that we
04:21have symptoms from hormone access,
04:23a measurable hormone in the urine
04:25or the blood,
04:25and then patients have true symptoms
04:28that are directly attributable to that.
04:30Carcinoid syndrome is a classic example
04:32of that happens in only about 10% of
04:35patients with small intestine Nets.
04:37In the picture you can see flushing
04:39on the cheeks and the nose that
04:41is classic for carcinoid syndrome.
04:43Pancreatic Nets also secrete
04:46hormones insulin, gastrin, Glucagon.
04:48For example,
04:49if a patient who creates insulin
04:51that can cause low blood sugar,
04:53it's more common to have a
04:56non functional net.
04:57So for this it's patients who are
05:00asymptomatic or their symptoms
05:02or not from hormone access.
05:05Let's also talk about the
05:06difference between stage and grade.
05:08These could.
05:08This can be kind of confusing,
05:10so stage I think of where is
05:12the cancer in your body?
05:13What is the extent of disease?
05:16We usually define this based on
05:19something called the AJCC staging
05:21criteria and that uses a scale of
05:23stages one through 4 and it depends
05:25on things like tumor location,
05:27size,
05:28lymph node involvement and metastatic sites.
05:31And here you can see these are two pictures.
05:33Doctor Abovyan will go.
05:34Through this later of a gallium
05:3668 PET scan and on the left in
05:39the middle is a pancreatic net,
05:41and on the right is a patient with
05:43pancreatic net that is spread to the liver.
05:46Now grade.
05:47On the other hand,
05:48is what do the cells look like under
05:50the microscope so we don't have a
05:51pathologist on our panel tonight,
05:53but they are critical member of the team.
05:55They look at these cells and can tell
05:57us is it low grade or slower growing
06:00or high grade and faster growing and
06:02these are primarily based on two features.
06:05One is called the Ki 67
06:07and another mitotic index.
06:08You may see those in your pathology reports.
06:11Those are markers of
06:13proliferation and as of 2019,
06:16the digestive World Health Association
06:19classification break Nets down
06:21into grade 1/2 and three and well
06:24differentiated and poorly differentiated.
06:27Primary site matters,
06:28we used to lump all Nets together,
06:31but we now know that they need
06:33to be researched and often
06:35treated in different ways.
06:37So I gave some examples here
06:39where Nets can originate.
06:40As I'd mentioned earlier,
06:42small intestine is one of the more
06:44common sites and many treatments
06:45are tailored based on primary site.
06:47It's probably worth mentioning
06:48that if you or if you know someone
06:51that has a net that has spread
06:53to another place like the liver,
06:55you don't also have liver cancer it.
06:57It maintains the properties
06:59from where it started,
07:01so it would always be called,
07:03for example a pancreatic net,
07:04but that has spread to the liver.
07:07And this is another theme that we
07:09will touch on Doctor Brian will touch
07:11on this as as well Doctor Poker.
07:13So somatostatin receptors are
07:15the perfect target.
07:16So my cartoon here in green
07:18is the somatostatin receptor.
07:20Imagine you have a large population
07:22you want to figure out who has the
07:24somatostatin receptor. You do.
07:26Gallium 68 pets.
07:28Can you select out those patients
07:30that have this medicine receptor and
07:32then let's say you have a therapy
07:35that targets that receptor using this.
07:37Same target for therapy and diagnostics.
07:39It's called Theranostics and
07:41we actually have a way.
07:43It's sort of.
07:44I'd like you to just think about it and
07:46try to remember this lock and key analogy
07:48so the lock is this medicine receptor.
07:51The key attaches to that lock
07:53and drags along with it,
07:55a radioisotope that we can use
07:57for imaging or for treatment.
07:59These are general treatment
08:01categories for Nets.
08:02We're not going to go into
08:03all of the details here,
08:04but somatostatin analogues,
08:07biologics,
08:08chemotherapy and peptide receptor
08:11radiotherapy are the four main categories.
08:15What I'd like to do is walk you
08:17through a little bit of a treatment
08:19algorithm of how we think about
08:21selecting therapies for patients,
08:23so this is a little bit busy,
08:25and on the next slide I'll give
08:27you a reference and we can make
08:29that available in the chat so
08:31the NCCN or national.
08:34Cancer Network is a guideline
08:36that physicians from but they also
08:38have a patient facing guideline
08:40and we have treatment algorithms
08:42that are based on primary sites,
08:44so this is an example of the lung guidelines.
08:47This is an example of pancreas and
08:50I'll just walk through this one
08:52so often we will start with either
08:55observation or octreotide or lanreotide.
08:57I should mention, by the way,
08:58that this is for patients with
09:01metastatic pancreatic net.
09:02Subsequent therapies could include.
09:04Overall, Mr.
09:05Student of these are both pills,
09:07capecitabine and Tim is Olumide
09:09are both types of chemotherapy.
09:11There also pills 177 Lu Dictate
09:15is the part that Doctor Abovyan
09:17will speak about later.
09:19These are not listed by number
09:21and So what that
09:22generally means is that we tailor
09:24the treatment to a specific patient
09:26based on how the patient is doing
09:28and what our goals of treatment are.
09:31So in for many patients with metastatic Nets.
09:34Our goal is Disease Control,
09:37and many of these agents can achieve that.
09:39There are some that can also
09:41achieve tumor shrinkage,
09:42and that's a conversation depending
09:45on symptoms of the patient and what
09:47we're what we're trying to achieve.
09:49This is the link,
09:50and again I will put this in the chat.
09:52It's a great patient, lay friendly
09:55guideline on these NCCN guidelines.
09:59I'm small, bowel is also.
10:00I'm in an example so I'm just going
10:02to end with a few parting thoughts.
10:04Whether you are newly diagnosed or have
10:06been living with your net for awhile,
10:08I want you to focus on understanding
10:10a few key basic principles.
10:11If your oncologist has not gone
10:13over these with you, please ask.
10:15These are good questions to
10:17bring in hormone status.
10:18What is your stage in grade?
10:20What is your primary site and do you
10:23have presence of somatostatin receptors?
10:26I'd like to leave you with
10:27some really positive thoughts,
10:28so we've made so many advances
10:30in the last 10 years.
10:31In terms of treatment and imaging,
10:33academic centers like Yale
10:35will have clinical trials.
10:37We will always talk to you about what
10:39clinical trials are available and
10:40what standard of care treatments are
10:43available and clinical trials are
10:44really the way we make progress and
10:46they are definitely reason for hope.
10:48So I am going to stop share.
10:51I'm going to pass the baton to my
10:53colleague Doctor John compliment.
10:56Hello there, can you guys
10:58hear me yes. Alright.
11:04See my screen.
11:13Not quite, it still looks dark,
11:16but maybe it's just thinking.
11:20Ah, there we go. There we go.
11:24Let's see if I can get my.
11:26Alright, can you see it still?
11:29Yes perfect alright good.
11:32So good evening, everybody welcome
11:34and thanks to the Cancer Center for
11:36organizing this and asking me to speak.
11:39I'm going to go pretty quickly because
11:40there's a lot to talk about with
11:42neuroendocrine tumors and a fair bit of
11:44the treatment doesn't involve surgery,
11:46so I'm going to try and give a very.
11:49You know top flight overview
11:51and some examples.
11:52I will tell you there are some pictures
11:54up of surgical procedures and specimens
11:58on these slides, not right away,
12:00but a little bit further so.
12:02Just a forewarning on,
12:04I'll try and remember to point it
12:06out before I get to those slides,
12:07but if anybody might want to turn off
12:10their monitor and just listen in if you
12:13don't want to see pictures from from, say,
12:17an operation, you may wish to do that.
12:19So without further ado.
12:21For this portion of the conversation,
12:24a few quick objectives we want to talk about.
12:28What are the indications for surgery?
12:29In other words, what it?
12:30Why would we take somebody to
12:32surgery for under consumer?
12:34Really a big focus,
12:35and I think Dr Kunz already alluded
12:37to this is that every case really
12:39requires an individualized approach,
12:41and there may be sometimes where
12:42folks with even a localized or
12:44under consumer can forgo surgery,
12:46and we'll talk about an example of that,
12:48and then we'll talk about what does
12:50surgery entail? What are some options?
12:52Uhm,
12:53and we're going to focus really
12:54on pancreatic,
12:55nor under consumers and small bowel
12:57and or under consumers as sort of the.
13:00Broad example,
13:00most common examples of those that
13:03are approached by surgery and then
13:05talked briefly at the end about
13:07what role surgery can play in
13:09metastatic under under consumer.
13:10So just starting with pancreatic
13:12nor under consumers,
13:13as mentioned by Doctor Kunz,
13:15you know the the biggest top level
13:17classification for pancreatic and under
13:19consumers is whether they're functional.
13:20In other words,
13:22are they secreting hormones?
13:23And that also tells us not
13:25only how the symptoms present,
13:26but also sometimes how they behave and some
13:28can behave in a more indolent manner like.
13:30Insulinomas and in the past,
13:32because virtually everybody with a
13:34hormone oversecretion would have symptoms.
13:36This is how people were diagnosed,
13:38but nowadays non functional
13:40neurons are consumers.
13:42Depending on which paper you read
13:43it can be almost three quarters
13:45or more of patients these days
13:48are diagnosed with non functional
13:50peanuts and they're diagnosed.
13:51Incidentally they can still have
13:53symptoms though if that peanut
13:54is large enough to call paint,
13:56cause pain,
13:57nausea or sometimes even jaundice.
13:59So here's an example of a CAT scan
14:00and I'm not going to do much.
14:02Imaging because we have some
14:03real experts later in the talk,
14:04but that's a pancreas on the CAT scan.
14:07If you've never seen one before and
14:09it's an important tool that we use
14:12to stage or determine where in the
14:14spectrum of grade and extent of
14:16disease each individual patient lies.
14:19So you know we want to characterize
14:20the tumor and
14:21you can see the tumor there
14:22with the yellow arrow on it.
14:23It's it's actually very easy to see
14:25in or under consumers of the pancreas
14:27because they do take up that Ivy
14:29contrast so well and are so bright
14:31and we use some other modalities.
14:33Including nuclear medicine, MRI,
14:34and sometimes endoscopy to stage
14:36and make the diagnosis and also a
14:38number of blood tests for both tumor
14:40markers and hormones if needed,
14:42prior to coming up with a treatment plan.
14:44Again, all these things can create
14:46small but sometimes very important
14:48and critical differences in how we go
14:50about treating patients with surgery.
14:52Kind of a theme of the talk is just that.
14:54Individuality.
14:54Like I said, if there are metastases,
14:56I think the good news is and this was
14:58already alluded to as well is that
15:00there are treatment options and there
15:01are many treatment options they're evolving.
15:03And they're growing,
15:04and sometimes surgery can be
15:06used for a localized pancreatic,
15:08nor under consumer surgery is really
15:10the primary modality for treatment.
15:12All functional neuroendocrine tumors.
15:13In other words,
15:14those that are secreting hormones,
15:16should be respected and in in patients
15:18that are good candidates for surgery
15:20and patients with non functional
15:21neuron are consumers of the pancreas if
15:24they're symptomatic causing those jaundice.
15:26So domino pain, those kind of things.
15:28But what about patients with incidentally
15:32discovered neuroendocrine tumors?
15:33You know, for localized disease,
15:35in other words,
15:37non metastatic disease,
15:38the biopsy and staging tests can
15:40really help to guide our behavior.
15:42So what are some things that could make
15:44us think that perhaps observation and
15:46no surgery might be the right way to go
15:49for a pancreatic nor under consumer?
15:50Well,
15:51if we see one of those lower grade
15:53lymph node or sorry lower grade tumors,
15:55tumors that have no lymph nodes that
15:57are enlarged that are suspicious for
15:59early spread and very small tumor size.
16:01So it's important to remember
16:03that all peanuts.
16:04Do have the potential to grow
16:05and spread all of them do so.
16:07They can't be ignored,
16:09even if they're small or or less worrisome,
16:11but we do know that for a subset of peanuts,
16:14the likelihood of spread is very
16:16low and I just want to touch on this
16:18because this is an area of controversy.
16:20Uhm,
16:20some of the data for this really
16:22has evolved over the last ten years
16:24and I just want to show you a few
16:26quick studies so you know one of
16:28the earlier ones came out of the
16:29Mayo Clinic and they looked at
16:30patients with tumors that were less
16:32than 4 centimeters in size.
16:33And this was a single hospital.
16:34Very small series,
16:35but it got everybody talking because
16:37it seemed to suggest that small tumors
16:39did just as well as larger tumors.
16:41If they had a resection or not.
16:43However,
16:44using even more restrictive criteria,
16:46a study out of Duke a few years
16:48later showed that patients
16:49that didn't have surgery.
16:50At a 50% worse survival than
16:52patients that were observed,
16:54it's really hard to reconcile
16:56those two pieces of data.
16:57A study from our institution looked
16:59at very small neuroendocrine tumors,
17:01tumors in a national database study
17:03and it showed that for very small
17:05tumors those under a centimeter,
17:0795% of patients were alive at 10 years,
17:10although some did develop lymph node
17:12spread and ultimately underwent surgery.
17:13So probably the best study came
17:15out in New York, where they looked
17:17at small tumors over four years,
17:18and this was a single institution, but.
17:20A very well controlled study and
17:22basically what it told us is that
17:24for small tumors the outcomes
17:25are the same if they're observed,
17:27but some of them will progress
17:29to needing a reception,
17:30so it's really important to watch,
17:32so the take home point from
17:34a surgeon standpoint.
17:35Are there pancreatic near under
17:37consumers that are safe to observe?
17:39Yes, but who are those candidates?
17:41So First off, like I said,
17:43they can't have any hormone hypersecretion
17:44they've got to be asymptomatic.
17:46No evidence of lymph nodes spread
17:49that very well differentiated
17:50or low grade pathology.
17:52A small tumor,
17:53and then most importantly they're
17:54amenable to follow up because we
17:57have seen patients that because
17:58the follow up has been LAX,
18:00have progressed and ultimately
18:02have tumor spread,
18:03that might have been resectable at
18:06one point and potentially curable.
18:09So what do we for patients that do need
18:11surgery that don't meet those criteria?
18:13What are our goals?
18:14So we want to maximize local control.
18:15What does that mean?
18:16We want to remove the lymph nodes
18:18around the pancreas because we
18:19know that the lymph nodes are
18:21frequent spot of early spread.
18:23Also,
18:23we want to get in our zero section
18:24or one with negative margins and we
18:26want to improve patients quality
18:28of life if they're symptomatic.
18:29And of course we want to minimize
18:31any complications from surgery.
18:33So how do we pick what operation to do?
18:35The tumor location is very important,
18:37whether or not it needs the lymph nodes.
18:39Removed is also very important and
18:41patient preference is also considered two,
18:44so enucleation is a technique that
18:46really just removes the tumor from
18:48the pancreas without removing much of
18:50the surrounding pancreatic tissue.
18:52Now that sounds great,
18:54but not all pancreatic neuron or
18:55consumers are amenable to this really.
18:58Only very small or very benign
19:00behaving tumors like insulinomas are
19:02candidates for this, most or not,
19:04and even for those type of
19:06reassuring tumors if they're close
19:08to this pancreatic duct.
19:09Here the complication rate goes
19:11very high if that duct is injured,
19:14so it's really a small number of
19:16patients that are candidates for it,
19:18and there's going to be some pictures
19:20now of some pathology and surgical cases,
19:22so there's there's the warning,
19:24but this is what it looks like
19:26after we perform the procedure.
19:27You can see the tumor there in
19:29the middle and just a little bit
19:31of normal pancreas around it.
19:33And this was an insulinoma
19:35this particular case,
19:36again, the number of patients that are
19:38candidates for that is quite small.
19:39If they are not candidates for enucleation,
19:43then the position of the tumor within
19:45the pancreas is really what leads to the
19:47decision and the big deciding point is
19:49whether it's in the head of the pancreas,
19:51in which case the Whipple procedure
19:53pancreaticoduodenectomy is the
19:54procedure of choice or the left
19:56side of the pancreas where a distal
19:58pancreatectomy is the procedure of choice,
20:00and sometimes that includes the
20:02spleen removed along with it,
20:04and sometimes not.
20:05So just talking a little bit more
20:08about distal pancreatectomy.
20:10It's for its tumor again.
20:11That's located in the body or
20:13tail of the pancreas.
20:14Sometimes it's performed open,
20:15but many times in fact,
20:17the vast majority of the time today,
20:19especially at Yale, we can perform
20:21it in a minimally invasive fashion.
20:23If the spleen needs to be removed,
20:25it's a case by case decision as I said,
20:27but if it does need to be removed,
20:29we can compensate for that lack of a
20:31spleen with vaccinations against a few of
20:33the organisms that the spleen helps with,
20:35so it doesn't affect one's life.
20:38Just a very quick video here.
20:41Skip the video.
20:42Very quick video if I can make it work.
20:46Let's see here.
20:48I guess I can't.
20:50I will try one more time.
20:55Think I have to go in here.
20:57Here we go. So this is a video of a
21:00laparoscopic distal pancreatectomy.
21:03What I'm doing here is elevating
21:05the stomach and getting into
21:06what's called the lesser SAC,
21:07and you can see the tumor is sitting right
21:09there with the white arrow pointed at it.
21:11The pancreas is running right and
21:13left on the bottom of the screen,
21:14so the first thing we do is mobilize
21:16and get that tumor elevated and
21:18completely get the pancreas lifted up
21:20there so we can see above and below it,
21:22and in doing that we can access the vessels
21:25that supply the pancreas and the spleen.
21:27In this case you see me
21:28holding the splenic artery.
21:29They're just about to come around it.
21:31That splenic artery supplies the spleen,
21:33and the pancreas.
21:34It's divided with a vascular stapler and
21:36then we fully mobilized the pancreas and
21:38divide it medial to where the tumor is.
21:41So we make sure we get that negative margin,
21:43and then once that's all done,
21:46we just pop it in a little plastic baggie and
21:48pull it out and that's all there is to it.
21:51After the surgery,
21:52just switch back here after the surgery.
21:55Patients usually go home in
21:56about three or four days.
21:57Sorry.
22:00It was in control of my.
22:03Presentation here.
22:04Well, suffice to say,
22:06they go home in about three
22:08or four days if all is well.
22:11For Whipple procedure,
22:12it's a bit more extensive.
22:13Most people are in the hospital
22:14about five or six days,
22:16and the reason it's more expensive
22:17is because the head of the pancreas.
22:19If the tumor is there,
22:21is unfortunately sharing a blood
22:22supply with all these other organs,
22:24so it is a bit more of an involved operation,
22:27but the remaining pancreas,
22:28the bile duct and the stomach
22:30are all reconnected and patients
22:32are able to eat and go about
22:34their their life lifestyle just
22:35as they did before the surgery.
22:37Once they recover.
22:37So a lot of patients ask me
22:39is pancreatic surgery safe,
22:41especially the Whipple.
22:42Procedure and it properly selected
22:44patients in properly selected
22:46institutions and surgeons.
22:47The answer is most definitely yes.
22:49So there's a very strong correlation
22:52between surgeon volume and also
22:54institutional volume for whether
22:55or not these procedures are safe.
22:58The reason that is it's not just the surgeon,
23:00but it's the nurses.
23:01It's the radiologist, it's the ICU doctors.
23:04It's so that if there is a
23:06complication it's recognized early,
23:07treated successfully and the patient is
23:10still discharged with a great outcome.
23:12So just for some examples,
23:14before COVID for five years at Yale,
23:16we were doing annually about 85 cases a
23:20year between the four surgeons that do them,
23:23which is an extremely high volume center.
23:27Just so you have some statistics,
23:29you know historically.
23:30The mortality for Whipple procedure,
23:32the length of stay was very long and
23:34the complication rate was very high,
23:36which is why it's still a
23:37very daunting operation.
23:38But nowadays,
23:39especially at Yale,
23:41it's a very safe operation and our
23:43outcomes in national databases are
23:45in the top ten percentile the nation.
23:47So just to summarize,
23:49like I said,
23:50the goals of the surgery are not
23:51just to control the disease,
23:52but improve the quality of life while
23:54minimizing the possibility for complications.
23:56There's those three major operations,
23:58and the choice of operation
24:00is largely dictated by.
24:01Where the tumor is and the outcomes are
24:03excellent when done at high volume centers.
24:05Just switching gears for
24:06the last minute or two,
24:07I want to talk about enteric
24:09neuron or consumers.
24:10Those in the bowel as Doctor Kunz alluded to.
24:13They can really arise anywhere,
24:15just as an example,
24:15because it's one of the more common ones.
24:17We'll talk about those
24:18to the small intestine.
24:20It's actually been the most
24:21common tumor because of the
24:23incidental findings since 2000.
24:24In the small intestine,
24:26only about 25 to 40% of
24:29patients present with symptoms.
24:31Uhm?
24:32You can see some obstructed bowel
24:34here on the left with the tumor there.
24:36And this is something called an
24:38intussusception where the bowel
24:40gets sort of inserted on itself
24:42and it also creates discomfort
24:44and and obstruction.
24:46But most are diagnosed incidentally
24:47because there's a very high
24:49incidence of lymph nodes spread
24:50into the mesentery and this
24:52mesentery is the structure where the blood
24:54vessels and lymph nodes run to the intestine.
24:56So what does that mean?
24:57We do the same kind of staging work up,
24:59but what we oftentimes see these lymph nodes
25:01in the mesentery and sometimes they're small.
25:04Like that sometimes a little bigger and
25:07sometimes quite large and they can be
25:09involving some of these major blood vessels.
25:11So when we take patients to the ER for
25:13a small bowel, nor under consumer,
25:15our goal is again to clear the primary tumor.
25:18But an important point is that many,
25:19many, many patients up to a
25:22third have multiple tumors.
25:24So if we use a minimally invasive approach,
25:26which we do when we can,
25:27we have to inspect the entire bowel.
25:29We also want to clear all those lymph nodes.
25:32And again we want to minimize complications.
25:34So in the last few slides just showing it.
25:36So when I talk about multifocality,
25:38here's a length of intestine and
25:40here you can see five separate
25:41tumors in that length of intestine.
25:43So when we do do the operation,
25:45minimally invasively,
25:46we use some tricks like this sleeve here
25:49this plastic sleeve to allow us to take
25:51the bowel out of the body and inspect
25:53it with still very small incisions and
25:55when there is mesenteric involvement
25:57on the major blood vessels like this,
25:59we sometimes have to do very careful
26:01dissections to remove a big portion
26:03of the mesentery while preserving.
26:05Those large arteries and veins,
26:06and here's just a few operative
26:09photographs and then the last slide.
26:11I just want to talk about
26:13surgery and metastatic disease,
26:14so sometimes surgery is the right answer
26:17for patients with metastatic disease.
26:19Generally,
26:19if the vast majority can be removed
26:22or sometimes all of it can be removed.
26:25Again,
26:25this can sometimes be done laparoscopically.
26:27Lee.
26:29And we can do this through
26:31fairly small incisions.
26:31Here's that piece of liver
26:33after it's been resected.
26:34So just in closing,
26:36like I said,
26:37patients really need to be
26:38managed on an individual level
26:40because there's so much nuanced.
26:41It's important to be at
26:43an experienced center,
26:44and the key considerations for the
26:45surgery is making sure all of the
26:47tumors and all of the lymph nodes
26:49are removed and carefully selected.
26:50Patients can still get a benefit
26:52even if there's metastatic disease.
26:54So last slide with just my partners in
26:57surgical oncology and our research staff.
27:00And I'll end it there and stick around
27:02for any questions at the very end,
27:04so I'll stop my sharing.
27:09After constant thanks so much,
27:10we're going to do questions all
27:12at the end, so Dr Madoff will join,
27:16and I'll just remind everybody to
27:18please put questions in the Q&A
27:20we're aiming for about 45 minutes
27:22total of some presentations,
27:24and then we'll leave plenty
27:25of time for questions.
27:27Thanks, doctor medical.
27:29OK, so if when you see my slides, yes,
27:32perfect. OK, great, so first I'd like to
27:35thank you Doctor Kunz and the Center for
27:39GI cancers at Smiley Cancer Hospital.
27:41For inviting me to speak tonight on
27:43the topic of liver directed therapies
27:45for neuroendocrine liver metastases.
27:47As you've already heard from both doctors,
27:49spoons, and kinsmen, there are now many
27:51surgical and medical options for this.
27:53Typically slow growing group of diseases,
27:56so the reason why I am speaking tonight
27:58is that despite these advances,
28:00the literature,
28:01including this study from Doctor James Yao
28:03at the MD Anderson Cancer Center in Houston,
28:06and our own clinical experience,
28:08has shown that the poorest
28:10prognostic variable is involvement.
28:12Of tumors within the liver.
28:15Therefore, I'm here to introduce you to
28:17the field of interventional radiology,
28:19and even more specifically
28:21interventional oncology,
28:22which has been used for a few decades.
28:24In the armamentarium treat patients
28:26in new endocrine, liver metastases,
28:28interventional oncology,
28:29or we now call IO is a subspecialty
28:33of radiology that utilizes minimally
28:36invasive procedures to diagnose and treat
28:38patients with various forms of cancer.
28:40The benefits of IO treatments are many.
28:42Our procedures are mostly done in the
28:45outpatient setting are often done with
28:47moderate sedation or local anesthetic,
28:48and without the need for general anesthesia.
28:51There is no surgical incision and instead
28:54we operate through small pin holes,
28:57which usually leave no scar.
28:59The procedures usually result in
29:02immediate tumor death are minimally
29:04invasive with being both cost and
29:07time effective and hopefully lead to
29:09a gentle patient experience because
29:11they are done with image guidance.
29:12They're very accurate with reduced
29:14risk of trauma to adjacent organs
29:16or structures and have minimal
29:18side effects that often lead to
29:20an improved quality of life.
29:21And Please note that interventional
29:24oncology is not radiation oncology.
29:27Fact Interventional Oncology is
29:29now become the fourth pillar
29:30of oncology joining medical,
29:32surgical and radiation oncology.
29:34IO therapies are now incorporated
29:37into multiple NCCN guidelines.
29:39We are valued participants in many tumor
29:41boards and we offer clinical trials
29:43that can further define the role of
29:46these treatments in overall cancer care.
29:48So there are multiple ways that
29:50intervention oncology can get involved
29:52in the management of patients with
29:54neuroendocrine liver metastases and
29:56includes diagnosis with pertanian
29:58image guided biopsy and treatments
30:00which include primary adjutant
30:02in neoadjuvant tumor therapy,
30:03postoperative complication management,
30:06central venous access palliation,
30:09and many others.
30:11So percutaneous.
30:12Image guided biopsy is now the standard
30:14procedure for most non palpable masses,
30:16allowing us to obtain diagnosis.
30:18And precise histologic analysis and
30:21this can therefore direct modality
30:23and order of therapeutic options,
30:25and in fact, because of its utility,
30:28percutaneous biopsies are really
30:29one of the most important procedures
30:32that I do on a daily basis.
30:34So this is a relatively standard
30:36treatment algorithm for treating
30:38patients with advanced neuroendocrine
30:40tumors to the liver.
30:42IO's role is highlighted here in red,
30:45you can see that we become
30:46involved when there is
30:47a need for convergence or respectability.
30:50And when surgery is either contraindicated
30:52due to comorbidities when the disease
30:55burden is highly complex or diffuse,
30:57and when patients are symptomatic
31:00and refractory to other
31:01medical types of treatment.
31:03So to clarify, we can convert patients
31:06to respectability by improving
31:07performance status and reducing
31:09the risk of postoperative failure.
31:12We can treat symptoms refractory
31:13to medical management and allow
31:15most patients to benefit from a
31:18sustained symptom free interval.
31:19Lastly.
31:20We can try to influence patients
31:22with progressive disease burden
31:24that is palliate those with bulk
31:26related symptoms will prevent those
31:28with marginal deterioration of
31:30liver function tests to progress
31:32to fulminant liver failure.
31:36So the main types of liver directed
31:38therapy first we see a procedure here
31:41called portal vein embolization,
31:42which has the main use of preoperatively
31:45growing the liver that will remain
31:47after a large surgery since the
31:49days of the ancient Greeks and
31:51the story of Prometheus,
31:52we have known that the liver regenerates.
31:54This procedure works by blocking
31:56most of the blood supply to the
31:58part of the liver to be removed
31:59and forced the blood to the part
32:01of the liver that will remain.
32:03This will lead to liver growth and therefore.
32:06Can reduce the number of overall
32:09postoperative complications and increase
32:11the number of patients who are at
32:13risk for liver failure after surgery.
32:15Next we have pretty nice oblation
32:17which has the goal of eradicating
32:20all viable malignant cells while
32:22sparing normal surrounding tissues.
32:24We can treat tumors with unfavorable
32:27distribution patterns or locations
32:29for resection and those with multiple
32:31comorbidities that are not able to have
32:34surgery for neuroendocrine tumors.
32:36It is often used in patients with low
32:39volume disease and for debulking there
32:41are many different types of ablation,
32:42ranging from heating,
32:44freezing and electrocuting tumors.
32:46They all have nuances,
32:47so the physician performing the procedure
32:50will need to be aware of these.
32:51These procedures are typically done
32:53as outpatient and are repeatable,
32:55but they do often require general anesthesia.
32:59Lastly,
32:59we have transarterial therapy that
33:01is often used for unresectable
33:03tumors in patients with progressive
33:06disease or are symptomatic or when
33:09liver involvement is at least 30%.
33:11It's also used for tumors in
33:13difficult or dangerous locations
33:14for resection or equation.
33:16The rationale for a transarterial approach
33:17is that the tumoral blood supply,
33:19largely derived from hepatic artery,
33:21and that we can deliver intravascular
33:24agents via selective catheter
33:26positioning under fluoroscopy
33:28and therefore minimize systemic
33:30complications and toxicities.
33:32There are currently three main categories
33:35of techniques which I will discuss shortly.
33:38So the typical way transarterial
33:40procedures are done is through a
33:42tiny incision in the groin and rest
33:44in each tuber catheter is advanced
33:46into the large artery in the abdomen.
33:48That's the aorta and then snaked
33:50into the liver arterial supply.
33:53Various agents toxic to tumors are
33:56then administered to kill the tumors.
33:58And here we see early and late phases
34:01of an arteriogram with the circles or balls,
34:05all representing a tumors that are
34:07filled with radio graphic contrast dye.
34:12So there are four main types
34:14of transarterial therapies,
34:15and they are all shown here,
34:16TE or bland embolization is
34:18the administration of small,
34:20biochemically inert beads that
34:22destroy tumor solely by causing
34:25ischaemia or lack of blood flow.
34:27Chemoembolization is divided into
34:29conventional and drug eluting beads.
34:31Each uses chemotherapy administered via
34:34delivery vehicle and oily substance known
34:36as lipiodol or bland beads that have
34:38been soaked in chemotherapy and then
34:41diluted chemotherapy into the tumor.
34:43Lastly, there is radioembolization
34:45whereby a radiation source,
34:47typically Y 90 or 1890,
34:50is attached to an inner particle
34:53infused into the tumoral blood supply.
34:56So how does one decide which type
34:58of therapy you should receive?
34:59Well, it's based on a number of
35:01factors that include disease,
35:02location and extent, such as the as
35:05diffuse or localized as we see here.
35:07There are numerous.
35:10There's procedural considerations,
35:11such as the advantages and
35:13disadvantages of each.
35:14There's tumor Histology.
35:16There is also the expected outcomes,
35:19such as what we find with bland embolization,
35:21working best for carcinoid,
35:24where chemoembolization actually works
35:26better for a pancreatic neuroendocrine,
35:29and of course patient preference.
35:31It's important for patients to
35:33understand that while we can
35:34advise and make recommendations,
35:36it's ultimately the patients
35:37choice for what should be done.
35:40So I wanted to just show in
35:41the next few minutes.
35:42It's just a few patient cases that
35:45highlight the liver directed therapy.
35:47Here we see a neuroendocrine tumor patient
35:49with multiple tumors throughout the liver.
35:51The liver remnant was deemed too
35:53small and we therefore performed
35:55a portal vein embolization.
35:57The left lateral liver,
35:59which we can see here grew and
36:03the patient therefore underwent a
36:06successful major liver resection with
36:09an uneventful postoperative course.
36:11Here we have a patient with
36:13carcinoid syndrome caused by this
36:15small tumor indicated by the arrow.
36:17There's two member was in a very
36:19difficult location and due to the
36:21carcinoid syndrome had two poor
36:23nutritional status to undergo surgery.
36:25I emboli as the tumor.
36:27The tumor got smaller and the
36:29symptoms resolved.
36:30She ultimately gained 30 pounds
36:32and the patient was therefore able
36:34to undergo the uneventful surgery.
36:38Here we see a small tumor,
36:40indicated by the white arrow,
36:42but the tumor was symptomatic
36:44is shown in the right liver.
36:46I used ultrasound guidance to place
36:48the probe into the mass and use
36:50microwave ablation to heat until
36:52the tumor and 18 months later
36:54this patient had no recurrence.
36:56This is another case of a patient
36:58with carcinoid syndrome who
36:59underwent bland embolization,
37:01again with inner inactive beads.
37:03After four rounds of therapy,
37:05you can see that on the right the
37:07tumors are much smaller and much less.
37:10Much less easy to see,
37:12and she therefore became symptom free.
37:15Here we have a woman with
37:17extremely rapidly progressive
37:18rectal neuroendocrine tumor.
37:20Despite systemic therapy.
37:21In fact,
37:22her tumors were growing at a control
37:23at a very short period of time and
37:25we were able to treat these tumors
37:27in all areas of her liver with
37:29multiple rounds of chemo embolization.
37:30Here we see massive necrosis of
37:33the tumors in the right liver,
37:35fortunately,
37:35were able to stop the progression
37:36and even treated tumors,
37:38and she's doing very well.
37:40And lastly,
37:40this is a patient with carcinoid who
37:42had diffuse tumors with radio and
37:45treated with radio embolization.
37:46We can see the numerous tumors
37:48and the right liver and scan.
37:50The Brimstone scan shown here,
37:53which shows the the radio embolization
37:56particles within the right liver,
37:59and this patient was treated with
38:00both in both lobes and ultimately
38:02had stable disease.
38:03I noted to be after one year,
38:06so before I finish I just wanted
38:07to bring to your attention the
38:10Redneck clinical trial.
38:11This is a study that's looking
38:12to compare the outcomes of bland
38:14embolization chemoembolization,
38:15although the drug eluting bead.
38:17Part of the chemo embolization
38:19arm has been stopped due to higher
38:21toxicity than had been previously expected.
38:24So, in conclusion,
38:25neuroendocrine tumor liver metastases
38:27therapies should be individually tailored,
38:30and fortunately,
38:30there are many side of reductive options
38:32to help with survival in palliation.
38:34Its therapeutic modality discussed does
38:37have advantages and disadvantages,
38:39but given the limited time,
38:40I was not able to go into much detail.
38:43Clearly,
38:43it takes a high level of expertise
38:46and considerable experience.
38:47To ensure good outcomes.
38:49However,
38:50if you do need such a treatment option,
38:52you should discuss in detail with
38:53your family and physicians which
38:55therapy may be best for you and
38:57suitable for your circumstance.
38:58And thank you for your attention.
39:02Thank you doctor math that was great.
39:04We will move now to Doctor Parker
39:07and then Doctor Brian will follow.
39:21Can you all see my screen?
39:24Yes, OK, great.
39:26So good evening everyone.
39:29Thank you for attending this
39:31session and also thank you Doctor
39:33Constance Milo for organizing this session.
39:35I will briefly discuss imaging
39:38focusing on the dotted scan and
39:40actually the quality of image Ng
39:43does matter because many of these
39:45tumors are small and we want to do
39:49our best really to detect them and
39:51also to look for their changes so.
39:55If you're diagnosed with
39:56new rendering tumors,
39:57domain scan that you will be receiving
40:00is either city or MRI of the abdomen
40:03and pelvis and as you have seen in
40:06prior imaging that has been shown,
40:08they are very well seen.
40:10But that's only because a
40:12special protocol was applied,
40:14so these otherwise subtle
40:16tumors can be well seen.
40:19When it comes to the dotted path,
40:22you probably heard that
40:23there are two options,
40:24one with the gallium and other with copper.
40:27But don't worry,
40:29are they actually performing very well?
40:32Clinically,
40:32both of them,
40:34and they have replaced prior octreoscan
40:36and he really these days you shouldn't
40:39be getting anymore deactivated scans
40:41because daughter taste so much better.
40:44However,
40:45daughter did is only complementary
40:47to see T and MRI.
40:50And it should be used critical
40:53junctions in your management.
40:55There is another type of the
40:57scan which is with the glucose,
40:59which you probably heard,
41:01because that's like a main pet scan.
41:03It's not used commonly in your endocrine
41:06tumors because fortunately tumors are less
41:09aggressive and don't take much of EVD,
41:12but if we occasionally suspect more
41:15aggressive tumor that is faster growing
41:18or so called your endocrine carcinoma.
41:21Is a more aggressive than typical
41:24in your endocrine tumors,
41:26we may actually use ABT scans.
41:32So this is a picture of our
41:35Siemens scanner at Yale,
41:37New Haven Hospital and I've I got the
41:40picture with two of my technologies and
41:43as you will see our technology is a great.
41:46They are very friendly and you
41:48would enjoy your visit with them.
41:50And don't worry.
41:51I mean it's not really scary.
41:53I mean yes for very close top phobic
41:55patients it could be a challenge,
41:57but most patients actually
41:59do very well with the scans.
42:01The scans are available from
42:03Monday to Friday and it takes
42:06about 25 to 40 minutes to perform.
42:09There are some small differences
42:11between the tracers and also
42:13depends on your height.
42:14Obviously if you are taller it will
42:16take a little bit more to do it.
42:20So this is an example of a normal
42:24dotted scan, and as you can see most of
42:27the activity is kinda in the abdomen,
42:30but you would also see a normal pituitary,
42:33normal salivary glands,
42:34and then in the abdomen you'll see
42:37normal levels, spleen, kidneys.
42:38There will be activity and the ball
42:41and some tracer will be excreted in
42:44the bladder and tracer is actually.
42:49Uh, targeting so called someone to
42:52Staten peptide receptors in the body
42:54and you will actually hear about
42:56these in all the lectures a little
42:58bit from the from all the speakers.
43:01And as you can see,
43:04the challenges that neuroendocrine
43:06tumors and normal activity is the kind
43:09of most frequent in this abdominal area.
43:12It can be busy,
43:13so that is why we use a so called
43:17cross sectional imaging very using the.
43:20Activity from data date with a CAT
43:22scan so we can localize precisely no
43:26both normal structures and the tumor,
43:29and I just want to mention something
43:31for your knowledge is that the pancreas
43:34and bowel which you were usually.
43:37These tumors originate have a
43:39normal variable activity in.
43:41Sometimes it can be confusing.
43:43So generally if someone suspects
43:45the tumor on the dotted scan,
43:48it would require ECT.
43:50For MRI validation or occasionally
43:53and endoscopy will be performed.
43:56But you cannot just use dot it alone
44:00without validating with CT and MRI.
44:03So this is an example of a metastatic
44:06well differentiated neuron,
44:07endocrine tumors,
44:08and these tumors that avidly take Dr.
44:11Tate,
44:12and they usually have activity
44:14more than normal levels.
44:15So you hear see metastatic disease
44:17in the level with the blue arrow
44:19and you see how the activity
44:21is above the normal level.
44:23And some of them can be as high to have
44:26activity above normal spleen and we
44:29have some scoring system that actually
44:32uses liver and spleen to actually
44:35classify the ability of these tumors.
44:37And as you can see,
44:39it's amazingly sensitive because
44:41this was actually very very tiny
44:44primary in the pancreas that later
44:47on metal styles in the liver.
44:49As you can see with the blue arrow
44:52and to the abdominal cavity.
44:54As you can see with the green arrow and
44:57the advantage of daughter to scan is
45:00that sometimes can detect either disease,
45:03either in areas that are not covered with
45:06the standard CAT scan or MRI or something.
45:08Sometimes the lesions that are not
45:11visible with standard CAT scan and MRI.
45:14Uh,
45:15and not commonly,
45:18but if you have a large practice like
45:21at Yale for your Android rumors,
45:23you will see a a fair number of people
45:26that have tumors in addition to yell
45:29at to the liver and abdominal cavity.
45:33Also in the skeleton.
45:34And this is where a doctor date
45:37is a particularly valuable because
45:39it would be very difficult to scan
45:42the entire body.
45:44With the CT or MRI and moreover DOT
45:46is also frequently more sensitive
45:49than this modality is particularly
45:51more sensitive than city,
45:53so if you have disease that is in the bond,
45:57you may actually be scanned more
46:00frequently with daughter did.
46:01Usually you get dotted the
46:03scans every one to two years,
46:05but you get can get more frequent order
46:07to scan if you have a skeletal disease,
46:09especially if someone
46:12suspects the progression.
46:14In the areas that are
46:15not covered by CT or MRI.
46:19Now, imaging interpretation is
46:22complicated and really expertise,
46:25and of the your readers do matter,
46:29and it fortunately all of us
46:32to see a lot of these scans,
46:35and we have a lengthy experience
46:38in interpreting those scans.
46:40So one thing which I would also have to
46:44mention to you when you are reading your
46:46report report is only the first step.
46:48The final decision on the response
46:51or progression is not made
46:53by uncle by radiologists.
46:55It is made by your oncologist,
46:57so you usually don't get alarmed
47:02with your report until you actually
47:04speak with your oncologist,
47:05which will put those findings
47:08in very better context for you.
47:11And one thing which also is important
47:13to mention is you don't get alarmed.
47:16Neuroendocrine tumors,
47:17chronic disease with which
47:19you would live for decades,
47:22so minor responses are minor progressions
47:24may not be clinically significant
47:26to justify the management change,
47:29so if they if someone describes some new
47:33small lesion that may not actually be
47:36serious or required management change.
47:40Size measurements are
47:41validated in city and MRI,
47:43but not on daughter date.
47:45So in order for look to the size changes
47:48you would have to stay with your main
47:51modality and one thing which everyone
47:53gets cares about is SUV changes,
47:56so that's a unit that we use to
48:00express activity on PET scans.
48:02But for your endocrine tumors
48:04and daughter date,
48:06these are not really clinically relevant,
48:09so increase in SUVs.
48:11Does not mean progression and decreasing
48:14as leaves does not mean response.
48:19And a little bit about the logistics.
48:22So again, your main modality would
48:24be either CAT scan or MRI, depending
48:27on the preference of young cologist.
48:29And for patients with metastatic
48:32neuroendocrine tumors on treatment they
48:35are usually recommended every three to six
48:38months for to look for changes in tumor size.
48:41If you have surgery,
48:43and especially if they were able to
48:46remove most of the tumor, all the tumors.
48:48The scan will be performed
48:50a little bit less frequent,
48:52usually at 6 or 12 months,
48:54to monitor for recurrence dotted path scans.
49:00Usually performed a diagnosis to
49:02determine the tumor spread or what
49:05would be the medical terms is staging
49:09the doctor Conser spoke about and then
49:12everyone to two years to look for areas
49:15of progression not detected by CAT
49:17scan or MRI of the abdomen and pelvis
49:21and prior to lutathera treatment which
49:24has revolutionized the field like
49:26Doctor Boy and will talk to you about.
49:29And occasionally,
49:31a rare patients with aggressive
49:35disease would receive a FDG PET scans
49:39and that would be some to be like
49:42a brief overview of the image Ng.
49:45Thank you.
49:48Doctor Packer, thank you.
49:49We will end up with doctor a boy and
49:52then we'll open up for questions.
49:54Can someone stop my share for some reason?
49:56I have hard time stopping.
49:58Oh OK, I was able. Thank you thanks.
50:16Take your time.
50:31I'll remind everybody to please
50:33keep putting your questions
50:35in the Q&A and we're trying to
50:37answer them as they come in,
50:39and we'll address some of them.
50:40Also at the end.
50:54Perfect Merriam that looks great.
50:58Thank you, thank you so
51:00much and thank you all
51:03the speakers for fantastic
51:04presentations and particularly Doctor
51:07Cooker for great overview of the
51:09imaging of neuroendocrine tumors.
51:12And I will address fairly quickly
51:16in terms of what is theranostics
51:19when we think about imaging,
51:22we think about CAT scans and MRI scans and a
51:25lot of the times we are seeing just anatomy.
51:28We see the liver, the vertebral body,
51:32the spleen, the stomach,
51:34the subcutaneous fat.
51:36That's that's what we see and
51:38how we interpret.
51:39We can also see a little bit
51:41in terms of where the tumor is,
51:42and so here's a couple of
51:44tumors in the liver.
51:45But we want to start seeing
51:47with nuclear medicine,
51:48and this is what was really exciting.
51:50Doctor Prakash presentation is to see
51:53beyond anatomy and to see into the function,
51:57so nuclear medicine allows us to do that.
51:59So here's an example of just seeing
52:02the anatomy and seeing the just basic
52:06imaging characteristics of the tumor.
52:08But we want to start heading towards
52:11this and you're looking at this
52:13right now and you're saying, well,
52:14actually this image doesn't look that good.
52:16It's it's kind of hard to see
52:19what's going on.
52:20I'm not even sure.
52:21Where the liver is here,
52:23and if you think about it,
52:26each cancer cell here is holding a light bulb
52:30and this light bulb is sending a signal.
52:33Hey,
52:34I am a very specific looking cell
52:37and that's what you're seeing here.
52:39You actually see tumors here that
52:41are in this particular patient.
52:43You also see some splenic uptake
52:45and some normal tissue uptake,
52:47but not so much majority of the
52:49signal comes from tumors.
52:50And if you look at the corresponding to.
52:53The see T you can see that piece
52:55tumors are not as easily seen without
52:58this fantastic agent called gallium
53:00Dotatate as Doctor Picard discussed just now.
53:04But what does that mean?
53:06What is this gallium dotatate?
53:08I know some of the students sometimes
53:10when they rotate with me they say Dodo.
53:12What? What is this though?
53:14Does tracer?
53:16Well it turns out gallium Dotatate
53:20will dissect it point by point.
53:23But it really allows us to visualize
53:27cells surface of the tumor and the
53:29receptors on that solid surface and
53:32the way it's able to visualize it is
53:35by the ligand that binds to the receptor.
53:38And because the ligand is radioactive,
53:41it lights up like a light bulb.
53:43And the reason why it lights up
53:46only on tumors is exactly how Dr.
53:49Kunz described the lock and key.
53:52The idea,
53:53so the receptor you can think
53:56of it as a lock and the lag,
53:59and you think you can think of it is a key,
54:01and there's a very specific interaction
54:04between the wagon dinner receptor.
54:06So when you're giving this radioactive drug,
54:10it goes specifically to the cells
54:12that have this receptor and targets
54:14those cancer cells that are holding
54:17up this light bulb and saying,
54:19hey,
54:19we're here and that's your
54:21how you're able to
54:23specifically target.
54:24Therapy to this location.
54:28How do we give the radioactive nuclide?
54:31Well, actually we want to be extremely safe,
54:34so we put it in a cage and it's
54:36a chemical cage, but you could
54:38think of it as a cage right here.
54:40So the radionuclide is located in the
54:43cage and then we attach the key to it.
54:47That will take it directly
54:49to the cancer cell.
54:50So this key takes this payload with
54:53it to destroy the cancer cells.
54:56So how? Let's dissect what this means.
54:59So the radionuclide you see right here.
55:02That's can be.
55:04We can pick any radionuclide.
55:06It could be the imaging radionuclide
55:08or it can be a therapy radionuclide.
55:10But here we're talking about the imaging.
55:12So gallium or copper.
55:15And then the cage is Dora,
55:18so that's what Dora means.
55:19It literally is just a cage,
55:21and it's ubiquitous.
55:22You can use the same cage for different
55:26radionuclides and then Tate is our
55:29actually targeting molecule the key.
55:32And when you combine them all,
55:33you get this payload and it
55:36goes into the body and directly
55:40finds these specific receptors
55:42and connects with the lock.
55:44So then you have the lock and key.
55:47And that's you were able to really
55:50target specific cells and the way
55:52we call it is gallium dooda Tate.
55:55So radionuclide cage and that key.
56:01That's basically how it works.
56:03Now, how does the therapy work well?
56:05The the cage and the key are the same,
56:09but the radionuclide is different so
56:12the radionuclide could be lutetium,
56:14actinium,
56:14or bismuth and we're working on these
56:17kinds of therapies at Yale to start
56:19bringing you these kinds of therapies so
56:22that we can provide the best care for you.
56:25And then the cage stays the same and
56:27the targeting molecule stays the same.
56:29The tape.
56:31So with this method you can
56:34actually image the patient.
56:36With the same drug then exchanged
56:38their radionuclide from the cage for
56:41the treat for the treating drug and
56:43treat the patient with the same drug.
56:45So you're basically providing
56:47very targeted therapy.
56:49And then the therapy will go straight
56:52to the somatostatin receptor and we
56:54will call it very similarly lutetium.
56:57So the radionuclide dooda the
56:59cage and Tate which is a targeting
57:01molecule or the key.
57:05And this is the basis for image
57:07guided therapy or therapy.
57:08Or as we know theranostics,
57:10we do the imaging with the imaging
57:13agent that gallium dotatate and
57:14then you can see all the tumors
57:16are lighting up throughout the body
57:19because they have this receptor and the
57:22cells are holding up the light bulb.
57:24I'm saying here we are.
57:25We're right here.
57:26We're expressing this receptor.
57:28Then we give the therapy
57:31with lutetium dotatate,
57:32which is identical drug as the gallium.
57:35To date, except the only thing that's
57:37different is the radionuclide.
57:39This is our imaging Euclid and this
57:42is our treatment radionuclide and then.
57:46We can actually do posttreatment imaging
57:48and we can see exactly where the drug went,
57:52which tumors the drug went to,
57:55and we can even estimate the dose the
57:58that the individual tumors obtained,
58:01and then we can send them to the
58:04interventional ecology and surgery
58:05for targeted therapy,
58:07as most greatly discussed earlier.
58:09So this therapy approaches is
58:13actually not very novel, but the.
58:16Approach to neuron decurrent
58:19tumors is very novel.
58:21And this therapy allows us to
58:23pick the right patient and use
58:26the right drug for the patient.
58:28Now the concept of targeted therapy
58:30has been available for a very long
58:33time and the idea for targeted therapy
58:36is to treat cancer by by targeting
58:38proteins and pathways that control
58:40how cancer cells grow and divide and spread.
58:43But when you give a drug that targets it,
58:46specific pathway or specific protein,
58:48there's no way you can target it to
58:52specific tumor cell with their Gnostics
58:55were actually able to image the targets.
58:58And make sure that the the patients
59:01tumors are expressing the targets
59:03that we're planning to attack,
59:05and then target the therapy and
59:08then see where the drug went and
59:10calculate the dose the tumor received.
59:13That is the advantage of theranostics,
59:15and it's the next kind of the targeted
59:21therapy 2.0 you can think of it that way.
59:24Now it's actually a very
59:27developing field right now and.
59:29You can see that over the last
59:32several years there's been a
59:34lot of advances in imaging of
59:37neuroendocrine tumors and therapy
59:39of new injecting tumors with different.
59:42Uhm, agents being an FDA approved,
59:45but it's not just neuroendocrine tumors.
59:47We're also the field is also developing
59:50therapies for prostate cancer for breast
59:53cancer and imaging agents as well.
59:56So this is an emerging field and we're
59:58jumping on this field at Yale by building
01:00:01out their Gnostics group here as well.
01:00:06Many of you have may have
01:00:08already read this article.
01:00:09This is the Seminole work that
01:00:11came out of the net of one trial,
01:00:14which is a phase three trial of
01:00:16lutetium dotatate from mid Kutner
01:00:18endocrine tumors and it led to FDA
01:00:21approval of the lutetium dotatate,
01:00:23or, as it's also known, ludera.
01:00:27Uhm, it, uh,
01:00:28the reason why it was approved was
01:00:30on the basis of prolonged progression,
01:00:32free survival and about 18% of the
01:00:37patient had significant tumor shrinkage.
01:00:39The treatment with Ludera is actually
01:00:41very well tolerated by most,
01:00:43with very few serious side effects.
01:00:47And the way this works is the principle
01:00:50of peptide receptor reuniclus therapy,
01:00:52or, as you all know it,
01:00:53as PRT when you inject the
01:00:56drug into the vein,
01:00:58it travels throughout the body,
01:00:59but then concentrates around the
01:01:01neuroendocrine tumor sites because
01:01:03the neuron decurrent tumors
01:01:04expressed the somatostatin receptors.
01:01:07Once these drugs are once lutetium,
01:01:11dority binds to the semester Staten
01:01:14receptors, the receptors get internalised.
01:01:17Or endocytosed inside of the cell.
01:01:21The lutetium is able to emit beta
01:01:24particles and result in DNA damage,
01:01:27which can cause tumor cell death,
01:01:30and that can actually cause
01:01:32some reduction in tumor volume.
01:01:34Or prevention of growth.
01:01:37So in conclusion,
01:01:39there Gnostics integrates diagnosis
01:01:41and therapy in a single flat platform.
01:01:44It allows to select right drug
01:01:47for the right patient,
01:01:49lutathera as a lot of you know,
01:01:51is an FDA approved drug for
01:01:53neuroendocrine tumors and has been
01:01:55shown to prolong progression.
01:01:57Free survival.
01:01:58And here at Yale,
01:02:00we are dedicated to develop and bring
01:02:03future theranostics and to help patients.
01:02:06Like you and really advanced the field
01:02:08so that we have better therapies.
01:02:15Thank you Doctor Brian.
01:02:16So great presentations.
01:02:18I really want to thank everybody.
01:02:20All of our speakers for their
01:02:22time and explaining things,
01:02:24and I hope for our audience that gave
01:02:26a nice overview of the state of both.
01:02:29Kind of what exciting advances we've
01:02:31seen in the last decade and really kind
01:02:34of some practical tips on understanding
01:02:37your net and on treatment options.
01:02:40So we've been trying to answer
01:02:41some of the questions in the chat.
01:02:42I may select a few of those as we.
01:02:46You know, go through our Q&A
01:02:47so this is the time.
01:02:48Please feel free to ask your questions.
01:02:51I'm going to start with just a
01:02:53few general ones and I'm gonna
01:02:55start with Doctor Kunstman.
01:02:56So we we talked a lot about the
01:03:00importance of multidisciplinary care for
01:03:02patients with neuroendocrine tumors.
01:03:04Can you describe what a tumor
01:03:06board is for our audience?
01:03:08And you know how we talk
01:03:10about taking care of patients?
01:03:13Sure. You know, a tumor board is a
01:03:18little bit of a misnomer because it's
01:03:20really a board of a lot of people that
01:03:23treats tumors to discuss patients.
01:03:25But essentially it's a group not
01:03:27unlike the one you see before us,
01:03:29but much larger, including.
01:03:33Possibly many surgeons,
01:03:34many medical oncologists,
01:03:36many radiologists, pathologists.
01:03:40Conventional oncologists etc.
01:03:41All of which are involved in
01:03:44treating a particular tumor type,
01:03:46site or location.
01:03:48Just as an example at Yale,
01:03:50we have a tumor board that specializes
01:03:53in neuroendocrine and related GI
01:03:56cancers that meets weekly and
01:03:58sometimes you know it's just a matter
01:04:01of a provider really wanting to find
01:04:04out if anybody else has any other
01:04:06ideas or about a change in therapy.
01:04:09Other times it's really an.
01:04:10Open conversation,
01:04:11but I think it's critical because
01:04:14obviously we're all very specialized
01:04:16in what we do and there may be
01:04:18things that one of us doesn't know,
01:04:20and it's actually critical.
01:04:21I think we've all said in the
01:04:23refrain from tonight that you're
01:04:25really treated by a group you're
01:04:27not treated by an individual,
01:04:29and you know the tumor board process
01:04:31is a critical part about that.
01:04:34Yeah, thank you. That's perfect.
01:04:36You know it includes our nuclear medicine
01:04:38physicians or interventional radiologists.
01:04:40All of the people on here are
01:04:42part of that team report.
01:04:43So Dr Madoff, I have a question for
01:04:46you about liver directed therapy.
01:04:48So often you know either
01:04:50myself or even at tumor board,
01:04:52will identify a patient that may be
01:04:55appropriate for liver directed therapy.
01:04:57There are a number to choose from.
01:04:58I don't pick what I generally
01:05:00refer patients to.
01:05:02I let you and your team
01:05:04really help pick which maybe.
01:05:06The optimal treatment for the patient,
01:05:07can you walk us through a little
01:05:09bit what goes into your mind about
01:05:11selecting between some of the available
01:05:13treatments that you mentioned?
01:05:14Yes,
01:05:15that's a great question.
01:05:17That is, you know a very difficult question
01:05:21because unfortunately at this time,
01:05:24and this is what the retina
01:05:25trial is supposed to figure out.
01:05:28Is a what? Is the best treatment
01:05:31for any particular disease so.
01:05:36Like I like, I had mentioned, UM,
01:05:39when patients have very low volume disease.
01:05:42If they have very small tumors and very what
01:05:45I would consider non challenging locations.
01:05:49Which means for example that if it's in the
01:05:52liver and it's small maybe 1 centimeter,
01:05:55it's not near any major arteries
01:05:57or veins or bile ducts.
01:06:00It should be easily treated with ablation.
01:06:05That being said,
01:06:05there are a lot of challenges where
01:06:08tumors are sitting in a really difficult
01:06:10location and either would be surgical.
01:06:13Candidates could even be potentially,
01:06:16I guess, and they're not here tonight.
01:06:17But radiation oncology patients but are
01:06:20right on a very difficult structure,
01:06:24so in those cases I probably
01:06:28would choose emblow therapy.
01:06:30Now between the envelope or
01:06:32the embolization therapies,
01:06:33there's a lot of nuances and that.
01:06:35Like I said,
01:06:35I haven't had really a lot of chance
01:06:37to get into all the details of them,
01:06:40but you know,
01:06:41for neuroendocrine where we know
01:06:44that patients live pretty long
01:06:46and hopefully prosperous lives.
01:06:51You know you have to also consider what's
01:06:53going on in the normal underlying liver.
01:06:55It's not simply the tumors,
01:06:57but it's also what is what you will
01:06:59be living with, because technically,
01:07:01the tumors themselves are not, even
01:07:04though they're you know they're function.
01:07:05It could be functional,
01:07:06they're not functioning as normal
01:07:08liver cells, so you only have you
01:07:11know so many liver cells,
01:07:12so you know you have to worry about the.
01:07:16I guess the collateral damage.
01:07:18OK, so I know there's been a lot of interest.
01:07:21In for example,
01:07:23review embolization radio embolization
01:07:24is as we discussed in outpatient therapy.
01:07:28It is because it gives radiation
01:07:32and not cause ischaemia.
01:07:34It doesn't typically result in a lot of pain,
01:07:37so the tumors themselves can,
01:07:40and there are also.
01:07:41It's also guided by vascularity,
01:07:44so these neuroendocrine tumors,
01:07:45as I showed are really hyper vascular,
01:07:49meaning that they are.
01:07:50They suck up tumors.
01:07:52In a very subtle treatment in a very big way.
01:07:55But you know when you're young,
01:07:57you're in your 40s and you have
01:07:59a therapy or you need a therapy.
01:08:02I pretty much try not to give
01:08:05radiation because there's only so many
01:08:07times you can give the radiation.
01:08:10I would say that it's not repeatable
01:08:12in the same way an ablation or
01:08:14another type of embolization is,
01:08:17so these are just thoughts.
01:08:19Always go through my head when I'm speaking.
01:08:22To a patient and you know what we didn't
01:08:24say is that part of interventional
01:08:26oncology is even though we're radiologists,
01:08:28we see patients the same way that you know,
01:08:31Doctor Prince Manor. Dr.
01:08:33Kunz see them. So I have my own clinic.
01:08:37It's not the way interventional
01:08:38radiology used to be practiced,
01:08:40but in 20 in the 21st century.
01:08:43And that's 2021, you know,
01:08:45we do formal consultations,
01:08:47go through the images,
01:08:49walk patients through the different
01:08:51types of scenarios.
01:08:53And it's actually very, I must say,
01:08:55enjoyable. Great thanks so much.
01:08:59Yeah
01:09:00that was that was super helpful.
01:09:01I mean, I think hopefully the audience
01:09:03can get a sense and I think one of
01:09:05the real keys takeaways from tonight
01:09:07is that we really try tailoring the
01:09:09treatment to an individual patient.
01:09:11So one size does not fit all.
01:09:13There are some general principles
01:09:15for how we treat patients with Nets,
01:09:17but we really do tailor the treatment.
01:09:20And many of those decisions
01:09:21are made at our tumor boards.
01:09:23So I have a question for Doctor
01:09:25Pickart was asked in the Q&A,
01:09:26but I'm gonna ask it just broadly so.
01:09:28Everyone can see the answer,
01:09:30so this is really around like thinking
01:09:34about can you speak about examples
01:09:36of the details showing lesions
01:09:37that are false positive you know,
01:09:39and I think that I think was really
01:09:41important as we were learning
01:09:43to read these scans.
01:09:44I think that expert centers were very
01:09:47familiar with what is false positive.
01:09:50Can you speak to that a little bit dark?
01:09:51Oh yeah,
01:09:53that's always a concern with any scan,
01:09:56regardless whether it's a nuclear
01:09:58medicine scan or an atomic.
01:10:00Can, because imaging is usually very,
01:10:03very helpful to find things, but really,
01:10:07the specificity sometimes comes for imaging,
01:10:10but usually for at least in the cancer
01:10:13requires a tissue confirmation.
01:10:16So undoubtedly specifically,
01:10:18the concerns are, for example,
01:10:21that inflammatory conditions can
01:10:24mimic neuroendocrine tumors and
01:10:26also there is a concern that other
01:10:28cancer in the body can take data.
01:10:30State and again creates the confusion.
01:10:33Now we have a so called craning scale which
01:10:37basically classifieds whether they are
01:10:39more active than level but less active.
01:10:43The spleen which should be called
01:10:45training tree and then the lesions
01:10:47that are more active than level
01:10:49would be craning 40 with the lesions
01:10:51of training tree and training for.
01:10:53We have a way more confidence that
01:10:56they are actually neuroendocrine tumors
01:10:59but again at any critical juncture.
01:11:03For the treatment,
01:11:04tissue confirmation would still
01:11:06be the gold standard.
01:11:08And I think we have one good question.
01:11:10I'm just going to try to kinda try
01:11:13to make it a little bit more broad.
01:11:15So basically if someone has pancreatic,
01:11:19had lesions,
01:11:20which endoscopic are ultrasound,
01:11:23couldn't confirm what would be the
01:11:26option I can start that we can for
01:11:29example do dotted scant and to
01:11:31demonstrate high activity above liver
01:11:33or spleen to increase the confidence.
01:11:36But we actually need a tissue.
01:11:39To determine Ki 67 and differentiation
01:11:42to guide the management.
01:11:44So I'm going to leave to A to our
01:11:47panel members to see how they
01:11:50would approach this situation.
01:11:52I completely agree and I think I
01:11:53might have answered that question,
01:11:55but yes, I I totally agree with that.
01:11:57I might turn to Doctor Brian and
01:11:59just ask a little bit about you know
01:12:02this peptide receptor radiotherapy
01:12:04that I think has really been a major
01:12:07advance in the landscape of patients.
01:12:10With nuts, can you talk us through
01:12:12the day of a treatment like what?
01:12:14What happens like when patients
01:12:16come in to get this treatment?
01:12:18I think there's a lot of fear
01:12:19because it's a form of radiation,
01:12:21but most of my patients I'll tell you,
01:12:23come back and stated me, Doc,
01:12:24that was a lot easier than I
01:12:26thought it was going to be,
01:12:27but maybe I'll let you walk us
01:12:28through what the treatment is like.
01:12:31Oh sure, thank you so
01:12:32much for great question.
01:12:34Uhm, so the day of treatment is
01:12:37actually pretty straightforward when
01:12:39we just started with PRT used to be
01:12:42a much longer day and but now we have
01:12:45much more advanced amino acid solutions,
01:12:48so the experience is much much much easier.
01:12:51We have a really nice therapy room
01:12:54on the 8th floor of the Smilow
01:12:57hospital and it's basically.
01:12:59You get a nice view and you
01:13:03stay in the nice in the room.
01:13:06The room is nicely protected
01:13:10and is lined with.
01:13:12Protective paperwork and also
01:13:15Chuck Stew and I'm sorry I should
01:13:17have included a picture of that.
01:13:20That would have been really nice,
01:13:21but you kind of will see everything
01:13:23is protected because we don't want
01:13:26any drops or radioactivity anywhere.
01:13:28You will receive your amino acid
01:13:30infusion and usually you're in a
01:13:33comfortable bed and then we will
01:13:36stop by and chat with you about the
01:13:39therapy and about how we will enter.
01:13:42Administer the therapy and discuss
01:13:43the side effects and the precautions
01:13:45for after the therapy and then
01:13:47will administer the therapy,
01:13:49which doesn't take very long.
01:13:50It's usually in the order
01:13:52of like 30 minutes and.
01:13:56Ivy and then after that, the immunotherapy.
01:14:00Will you know,
01:14:01I said infusion will continue
01:14:03and you will be discharged,
01:14:05so it's pretty straightforward process.
01:14:07It's not very exciting,
01:14:08but that's how we like to keep it.
01:14:11And then we'll spend a lot of time
01:14:14just chatting during the infusion.
01:14:16So
01:14:17thank you, yeah,
01:14:18and just to follow up on that.
01:14:20So the amino acid infusion for everybody
01:14:22is to help protect the kidneys.
01:14:25This was. Sort of started like decades
01:14:28ago when this therapy was originated
01:14:30in Europe and it originally used
01:14:32a combination of amino acids that
01:14:34caused quite a bit of nausha now
01:14:36only uses two amino acids called
01:14:39arginine and lysine and and those
01:14:41tend to not 'cause as much nausha,
01:14:44so it's a much better tolerated.
01:14:46In total it's about a four
01:14:48to six hour and infusion,
01:14:49and it's given every two months for
01:14:52a total of four doses is really
01:14:54the standard course just to get.
01:14:57Get focused and sense of that,
01:14:58so thanks, Marion.
01:15:00I'm gonna try to go back to the
01:15:02Q&A and and try to answer a few
01:15:04questions so one I will try answering.
01:15:06So does your clinic have a specific
01:15:09approach to sequencing order of treatments,
01:15:11especially for well differentiated
01:15:13grade three nor under consumers.
01:15:15So I'll mention that this is
01:15:18a relatively new category,
01:15:20as I mentioned in my talk,
01:15:22new under consumers are broken up into
01:15:24this three main buckets grade one,
01:15:26grade two and grade three,
01:15:28also by degree of differentiation.
01:15:31The well differentiated tumors tend
01:15:33to look more like the normal cells in
01:15:36that organ and poorly differentiated
01:15:38tumors tend to look very different
01:15:40and kind of disorganized cells
01:15:42different than the primary organ and
01:15:46so well differentiated generally
01:15:48means that it's slower growing.
01:15:51But grade three is in the faster
01:15:53growing bucket,
01:15:54so I tell patients we usually
01:15:57borrow from both treatment buckets.
01:15:59We worry that these may be a little bit.
01:16:01Faster growing,
01:16:01but we can often use therapies that
01:16:04are reserved for the slower growing tumors,
01:16:07and the question is a great one.
01:16:09And actually this answer
01:16:10generally applies to all Nets.
01:16:12We don't have clinical trials or data
01:16:15that helps guide which what order
01:16:18in which to give these treatments.
01:16:21We are in a fortunate place right
01:16:22now to have a number of therapies,
01:16:24but we don't yet know which one
01:16:26we should start with necessarily,
01:16:28and this is what where we then really
01:16:30tailor the approach to a given.
01:16:31Patients, so for example,
01:16:34if someone is having symptoms,
01:16:36IE pain from spots in the liver
01:16:38or pain from somewhere else,
01:16:40maybe we need to use something
01:16:43that shrinks the cancer.
01:16:44If someone is having symptoms
01:16:46from hormone secretion,
01:16:47we maybe need to use a therapy that
01:16:49helps lower those hormone levels.
01:16:51So all of these things are discussed
01:16:53with this entire treatment team and
01:16:56we help come up with the best plan.
01:16:59I'm gonna answer or ask another
01:17:00question and see if anyone from the
01:17:03group wants to try to answer this.
01:17:05So how common is it for Nets to be a
01:17:08precursor for other forms of cancer?
01:17:10For example bladder cancer or lymphoma, Dr.
01:17:14Kunzman. Do you feel like tackling that one?
01:17:18Yeah, I mean, I think that's
01:17:19actually a very good question,
01:17:20because whenever we talk about.
01:17:23Cancers that can have a more indolent
01:17:26course such as neuroendocrine tumors.
01:17:30It naturally creates a
01:17:32question in your mind you know,
01:17:34is it leading to something more aggressive.
01:17:36Now in the case of bladder cancer?
01:17:38For lymphoma or colon cancer etc etc.
01:17:42Now those are totally distinct entities
01:17:45and neuroendocrine tumors are not
01:17:48precursors pursy to other forms of cancer.
01:17:52So the answer to that question is no,
01:17:55but certainly we do see the
01:17:57differentiation status and the grades
01:18:00sometimes evolve overtime and a
01:18:02previously indolent neuroendocrine
01:18:04tumor can become more aggressive.
01:18:06That's why I think there was one of the
01:18:08questions the chat box about you know,
01:18:10a diagnosis and once removed,
01:18:13what's the next steps?
01:18:15That's why surveillance,
01:18:16and really a long term relationship
01:18:19with your neuroendocrine team
01:18:21is so critical to sort of.
01:18:24Find out about those changes as soon
01:18:27as possible and whether you know the
01:18:28way to mitigate it is with a therapy.
01:18:31Yep, great, thank you.
01:18:32Well we have about 10 minutes left
01:18:34and I am going to end by going around
01:18:37and asking all of our panelists
01:18:38what they're most hopeful about in
01:18:41the field of Narendra consumers.
01:18:43What where you hope to see the field go?
01:18:45Specifically what you do,
01:18:47and I'm I'm going to start
01:18:50with Doctor Madoff.
01:18:52Sorry to put you on the spot,
01:18:54this is a hard one because as we discussed,
01:18:59I mean interventional radiology
01:19:01interventional oncology has been
01:19:04actually at the forefront for
01:19:06like maybe close to four decades.
01:19:09I used to work at Indy Anderson
01:19:11in Houston and we had some of the
01:19:14pioneering work on envelope therapy for
01:19:16for carcinoid and and and the light.
01:19:20So I would I think would be great
01:19:23and I guess Merriam had kind of
01:19:26alluded to is how interventional
01:19:28radiology or interventional oncology
01:19:31could play a role in theranostics.
01:19:34You know there's been talk
01:19:38years ago about nanomedicine?
01:19:40And, uh, you know the idea was
01:19:43that you have this, you know,
01:19:45nanotechnology that then gets,
01:19:47you know, to the exact target.
01:19:50However, it's been found that
01:19:52most of the most of the material
01:19:55injected never actually makes it.
01:19:58To the target.
01:19:59So you have a lot of stuff
01:20:00going to the target,
01:20:02but you don't actually,
01:20:03but most of it degrades in advance.
01:20:05So with imaging and imaging guidance
01:20:08we could localize these kinds
01:20:11of therapies to the tumor itself
01:20:14without having to go through all
01:20:17the other circulatory issues.
01:20:20And in that way would be able to get a
01:20:23much better and like we talked about,
01:20:25targeted therapy.
01:20:28Great thank you. Maybe I'll
01:20:30pass to Doctor Abovyan next.
01:20:34Thank you well, I went
01:20:38into nuclear medicine when I saw PRT as
01:20:42I was training at UCSF and I was just
01:20:46blown away by these amazing therapies.
01:20:48But I just remember watching the
01:20:51tumors after party and majority of the
01:20:54patients did not have the tumor shrink.
01:20:56Yes, they'll have.
01:20:58They had improved progression free survival,
01:21:00but the tumors were not drinking as much as.
01:21:04As I would like to come so
01:21:06we have a fantastic key,
01:21:09but I really want that radionuclide
01:21:11that will make him shrink.
01:21:12So I think that's where we're going
01:21:15to be heading to and testing the
01:21:18radionuclides that can potentially
01:21:19make these tumors shrank.
01:21:22And also of course,
01:21:23work with Doctor Madoff and
01:21:25Doctor Parker and Doctor Kunz and
01:21:27Doctor Kuzman for for building
01:21:29Arthur Gnostics Center so.
01:21:33Great thanks ma'am.
01:21:34Yes, I'm excited about that too.
01:21:36So doctor Pukaar,
01:21:37what are you most hopeful about?
01:21:40Uh, well short term,
01:21:42obviously we need to develop alternative
01:21:45centers because we we actually
01:21:49expect explosion of these therapies
01:21:52vote for new rendering tumors,
01:21:54but also for the other cancers.
01:21:55There are a lot of exciting agents coming
01:21:59now in terms own on more scientific level.
01:22:03Probably the goal for your endocrine
01:22:06tumors is to basically have that
01:22:09run into real chronic disease.
01:22:11Doesn't shorten the lion and
01:22:14doesn't produce morbidity,
01:22:16so one of the thing on the imaging site.
01:22:20It would be good for us to develop a
01:22:24little bit different imaging criteria
01:22:26which would not lead us to change or
01:22:28do therapist too frequently before
01:22:31actually the other prior therapy
01:22:34is not really stopping working,
01:22:36which I I think will probably have to
01:22:39make make a criteria that are specific to.
01:22:42Neorion Deklin tumors will,
01:22:44because of other cancers,
01:22:45are more aggressive and those criteria
01:22:48probably are too aggressive for
01:22:50your endocrine purposes and then
01:22:52obviously which everyone is loading.
01:22:54I mean, in theory,
01:22:56if you can minimize the toxicity
01:22:59to surrounding tissue,
01:23:01you can actually theoretically
01:23:03deliver the dose that would eliminate
01:23:06all your cancers from your body.
01:23:08No one that ever reached so far
01:23:12because it toxicity to the.
01:23:14Normal tissue is was always too limiting,
01:23:17but there is at least that are
01:23:20at a theoretical goal.
01:23:22And just to mention along those lines
01:23:26will be getting a probably by the
01:23:29end of the next year at machine,
01:23:31which is called reflection,
01:23:33which can use the pet guidance
01:23:36to eliminate a lot of metastatic
01:23:40sites with radiation which is going
01:23:43to add another excellent.
01:23:44Way to minimize your tumors and
01:23:47really enable you to live long
01:23:50and prosperous life without you
01:23:52rendering tumors defining you,
01:23:54but rather you living your normal life.
01:23:59Thank you Doctor Kinsman any final thoughts?
01:24:02Things you're hopeful for. Yeah,
01:24:04I have to say actually the thing
01:24:06I'm hopeful for is the other
01:24:08people on this call because.
01:24:11You know, as I think we let me explain,
01:24:15what I mean by that.
01:24:16So as I think you may have gathered,
01:24:19you know some of the surgeries that
01:24:20we do are technically quite complex,
01:24:22but there's a limit to what we can do in
01:24:26the operating room in terms of who's a
01:24:29candidate for surgery and through the work,
01:24:32both from a diagnostic standpoint.
01:24:35So theranostic standpoint and you know,
01:24:37right now, I think Doctor Madoff
01:24:39alluded to some of his techniques.
01:24:41We're operating on and potentially
01:24:44curing people that would have never been
01:24:48candidates for surgery just a few years ago.
01:24:52You know, when I was in medical
01:24:54school and I was starting the journey
01:24:57to becoming a surgical oncologist.
01:25:00You know people were saying, well,
01:25:01by the time you finish your training,
01:25:02you know cancer.
01:25:03It's all going to be figured out.
01:25:04You know you're not gonna.
01:25:06You're not gonna need anything.
01:25:07You're not gonna have anything to do.
01:25:09In reality, we're busier than ever,
01:25:11because patients that previously
01:25:14were basically told, you know,
01:25:16we can only offer you best supportive care.
01:25:19You know,
01:25:20potentially through portal vein embolization.
01:25:24You know we can reset that liver
01:25:27tumor potentially through.
01:25:28You know, pet dotate.
01:25:30We can identify that last reservoir
01:25:32of disease and taken out,
01:25:34you know, so it's a really,
01:25:35really exciting time, I think.
01:25:38And you know,
01:25:39surgery is like the only field in
01:25:41medicine that's actively working
01:25:43towards its own obsolescence.
01:25:44But you know,
01:25:46I'm more excited than ever because there's
01:25:49so many folks that were able to help now.
01:25:52That perhaps you know,
01:25:53in the very recent past didn't
01:25:55necessarily have those kind of options,
01:25:57so that's it's a time of really good,
01:26:00great excitement.
01:26:02Great, thank you know I I
01:26:04share the hope on this call.
01:26:06Mentioned by all of the speakers,
01:26:08and I think you know,
01:26:09having I've been in this field now
01:26:11for about 12 years and I think you
01:26:13know over the course of that time,
01:26:15I've taken care of some patients for
01:26:17that entire duration of time and they
01:26:20in their lifetimes have benefited from
01:26:22clinical advances through clinical trials.
01:26:24So I think I'm really hopeful
01:26:26about these advances also,
01:26:28so I just want to thank the speakers
01:26:29so much for their time tonight.
01:26:31I want to thank the audience for
01:26:33your listening and participation.
01:26:35This the this whole talk.
01:26:37Will be available online so
01:26:38you can go back to it.
01:26:39You can share with your friends and family.
01:26:43We're certainly available for for
01:26:45questions and or consultations,
01:26:48but thanks,
01:26:48we're excited to really build the.
01:26:50Net community at Yale.
01:26:52So thanks everybody.