The Yale Center for GI Cancers: Challenges and Opportunities

May 18, 2021

Information

Yale Cancer Center Grand Rounds | May 18, 2021

Pamela Kunz, MD and Mandar Deepak Muzumdar, MD

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00:00OK, why don't we? Oh, get started.
00:05We have a good number of
00:08people on the line now.
00:10Welcome to grand rounds.
00:12Today May 18th, 2021.
00:14We're focusing on GI cancers today,
00:16challenges an opportunities and
00:18we'll hear from two members
00:20of that newly formed center.
00:23It was actually the first official
00:25disease center that we formed,
00:27and it's fitting that we
00:31have these two speakers.
00:33And what we'll do is we'll have each
00:36speak for 2025 minutes and then
00:38we'll do some questions right after.
00:41So the first is Doctor Pan Kunz,
00:44who is associate professor of internal
00:46medicine and medical oncology,
00:48and the director of the Center for
00:50GI Cancers and the and the and
00:53the Chief of GI Medical Oncology.
00:56And we're really fortunate to have Pam here.
00:59She's been here less than a year.
01:01She moved from Palo Alto, Atherton.
01:04And two New Haven during a very
01:06tough year to travel.
01:08So we're so happy you came Pam.
01:11She received her medical degree
01:12from Dartmouth Medical School and
01:14Residency and Fellowship at Stanford.
01:16She then state was at Stanford until
01:19she joined us in 2020 at Stanford.
01:21She was the director of the Stanford
01:24Neuroendocrine Tumor Program,
01:25the leader of Endocrine Oncology
01:27Research Group and the Director of
01:30the Neuroendocrine Tumor Fellowship.
01:32As you all probably know,
01:33she's an international leader in
01:35the clinical care of patients
01:36with neuroendocrine tumors.
01:37We call those Nets and ETS and is
01:39advancing the field through clinical
01:41trials and translational research.
01:43She's got a broad investigation or program
01:46and you're going to hear today about her,
01:48her plans,
01:49and what she's already initiated
01:50to really build her own program.
01:52But more importantly,
01:53the entire Geo program here at the Yale
01:56Cancer Center Smile Cancer Hospital,
01:58so Pam,
01:58thanks for being here today and
02:00I'm looking forward to your talk.
02:04Thank you, right?
02:07And right just give me a thumbs
02:08up but can you see my screen OK?
02:11OK, excellent good.
02:12Well thank you everybody and where I
02:14thank you for that kind introduction.
02:16I'm very excited to share with
02:18you our GI cancer program.
02:20But before we jump in I just want
02:22you to save the date for a very
02:25exciting grand rounds in two weeks.
02:27See we're having our first annual
02:29yield Center for GI cancers.
02:31Visiting lectureship with
02:32Doctor Marcia Cruz Korea.
02:33She is a professor of medicine
02:35and biochemistry and the director
02:37of the GI Oncology Program at
02:39the University of Puerto Rico.
02:41She has held leadership roles in ACR,
02:43most recently the women in
02:45Cancer Research Committee and she
02:47was the chairperson for that.
02:49The focus of her research is
02:51understanding genetic and AP
02:52genetic pathways for colorectal
02:53cancer among Hispanic patients.
02:55So we're very excited to host
02:57her in a couple of weeks.
03:01So I will be sharing the virtual
03:03podium today with Doctor, Mandar,
03:05Mazumdar and we are excited to
03:07share with you an overview of the
03:10program and some of the goals Mander
03:12will take on the scientific vision.
03:18So I'd like to start off just by
03:21recognizing that this is a an
03:23incredible team effort and what I
03:25will be talking about today really
03:27is the work of the entire team.
03:29It's been a pleasure to get to meet.
03:32Everybody will be at mostly
03:33by zoom over the last year,
03:35but we have really tremendous
03:37team members and have started
03:40also doing some recruiting.
03:42These are my disclosures,
03:43so I will take on providing you a
03:46background on GI cancers talking about
03:48this newly launched center and then
03:50I'll speak about our patient care,
03:53education and clinical research
03:54initiatives and then I will pass
03:57the baton to Doctor Mazumdar.
03:59So first just a brief background
04:01on GI cancers and aspects that
04:03make up make our center unique.
04:05So if you try to count up all of the
04:08different primary sites in the GI system,
04:11there are at least 12.
04:12Depending on how you count them,
04:14and I think that poses both some
04:17challenges and some opportunities as
04:18we think about developing a center
04:20and really trying to address all of
04:23these different primary sites via all
04:25of the main pillars of patient education,
04:27patient care, education,
04:29and research.
04:30In terms of estimated new cancer cases,
04:33colon, rectal and pancreas are in
04:36the top 10 for both men and women.
04:40However,
04:40there is a larger proportion attributed
04:43to GI cancers or estimated deaths.
04:46In fact,
04:4727% of estimated deaths in men or due
04:50to GI cancers that school in pancreas,
04:54liver,
04:54and oesophageal and for women it's about 21%.
04:58Colon,
04:58pancreas and liver.
05:02We've also had a number of FDA
05:04approvals over the last 12 months.
05:07This is since May of 2020 in fact,
05:10just in the last six weeks we've
05:12had three new FDA approvals in the
05:15immunotherapy space for advanced Asafa Geo,
05:17GE Junction, and gastric cancers.
05:19You'll see in those last three rows
05:22Pembroke Plus for permitting nivo plus
05:24floor permitting and Pembroke Plus
05:26tries to the map in floor permitting.
05:29So it's been very exciting for us.
05:33GI cancers have also been in the
05:35news quite a bit in the last year,
05:38which I think has done a lot to raise
05:42awareness, which is quite important.
05:43So Chadwick Boseman sadly died at a
05:46very young age of colorectal cancer.
05:48Ruth Bader Ginsburg died of
05:50metastatic pancreas cancer.
05:51We've also seen recommendations for the
05:53colon cancer screening age to drop to age 45,
05:56and this is on the basis of a
05:59draft recommendation from the
06:01United States President.
06:02Preventive Services task force.
06:03For average risk, adults age 45 to
06:0649 that they should start screening.
06:09This is not been put into practice just yet.
06:14So in terms of our center,
06:16I think Kevin best for this slide.
06:18Many of you have seen this,
06:20but Roy and I are in a bit of a competition,
06:24so both of our centers have launched.
06:26We went.
06:26We just edged out the thoracic center,
06:29but it's very exciting and there
06:31are 13 more centers yet to launch.
06:34These centers, I think,
06:36as many of you know,
06:37have a shared organizational
06:39structure with a leadership cabinet.
06:41There are common rules in all
06:43the disease centers.
06:44These include the director,
06:45and I will be serving that position
06:47for our center patient care Services
06:49Director Maureen Major Campos and
06:51Operations and planning director.
06:53Which is Kevin best?
06:55I also have a scientific director,
06:57doctor Mandel, Razum Dar,
06:59which I'm very excited about it.
07:00I'm currently serving an interim
07:02role as the clinical director.
07:04We also have the flexibility of
07:07adding a number of ad hoc rules
07:10specific to GI cancers.
07:12We wanted all of the relevant stakeholders
07:15to have a place in this leadership cabinet.
07:19So these include Sir junk education,
07:21cancer imaging, RAD ONC pathology,
07:23and Network Director,
07:25biorepository advanced endoscopy
07:26and importantly,
07:27a liaison with the GI service line.
07:31You'll see that that GI service line
07:33dotted line is really indicated
07:35to represent a bridge with our
07:37program at Doctor Mario Stresa.
07:39Bosco has done a wonderful job
07:41building a liver cancer program over
07:43many years and we still plan to work
07:46very closely with he and his team.
07:48In addition,
07:49we have started and launched
07:50for disease specific programs,
07:52including pancreas,
07:53neuroendocrine advanced hepatic
07:54bilary and colorectal ING.
07:55Alone.
07:55I'll speak about those in just
07:57a moment and we have some tumor
08:00boards that match up with these,
08:02which we will also talk about.
08:06So we have implemented some
08:07new meetings on the yellow.
08:09The yellow Star indicates things
08:11that have been implemented newly
08:13in the last year, so we have had an
08:16existing trimmer but actually just
08:17yesterday we launched a split, so this
08:20is now a single hour and a half meeting,
08:23but we have an upper GI pancreas net tumor
08:26board and a colorectal **** tumor board.
08:28The Liver Tumor Board is still on Thursdays.
08:31We have our existing DART
08:33clinical trial review,
08:34but we started a Center for GI.
08:36Cancer Seminar series on Thursday
08:38afternoons that consists of Journal
08:41club being led by Doctor Christie Gomez.
08:43Scientifiche talks clinical talks
08:45and industry pipeline talks.
08:47In addition, we've started a number
08:49of working groups and committees.
08:51This includes a GI tumor board
08:53revamp working group.
08:54This initial phase has concluded,
08:56but we will continue to meet quarterly
08:58a GI multi D Clinic working group.
09:00We started this in March and
09:02or having monthly meetings to
09:04pilot some multi D clinic switch,
09:06I will speak about on a later slide.
09:09We have leadership cabinet meetings
09:11and program leader meetings.
09:13So we've been quite busy.
09:15So I'll speak next about our
09:17disease programs.
09:18I want to mention some shared
09:20themes that I won't repeat on
09:22some of the specific slides,
09:24but we all envision in the pancreas,
09:26colorectal advanced hepatic bilary,
09:28and net programs to focus on these pillars.
09:31So multi disciplinary clinics,
09:32tumor boards,
09:33care coordination really
09:34important to GI cancers,
09:35integration of palliative care
09:37and we actually just have newly
09:39recruited Doctor Laura Baum who is
09:41pallative care and he Monk trained.
09:43She will join us this summer.
09:46In terms of education,
09:47we plan on expanding physician
09:49education and CME events,
09:51patient education events,
09:52mentoring with shovel ready,
09:54projects for trainees,
09:55and plan an advanced fellowship
09:57in GI Oncology for research.
09:59We hope to expand on clinical trials,
10:02specifically Iits.
10:03That's something that we need to
10:06increase in our portfolio and I
10:08will let Doctor Mazumdar speak
10:10later about some of our basic and
10:13translational research efforts.
10:14And then Lastly,
10:15advocacy.
10:16I'd like to think of this as the
10:19fourth pillar,
10:20and particularly in my role as the Vice
10:22Chief for DTI and getting more involved
10:24with community engagement and HealthEquity.
10:26I'd like for us to think about these
10:29aspects as we do all of our patient care,
10:31education,
10:32and research.
10:33So the pancreas program is being Co led
10:36by doctors Jill Lacy and Mandar Mazumdar.
10:39And in terms of patient care
10:42would I have done on these sides?
10:44Is underlying some of the key aspects
10:47that are unique to this program
10:50so they have planned a pilot,
10:52pancreatic cancer multi D clinic with
10:54a focus on non metastatic disease.
10:56We have just recently started point of care.
11:00Germline testing with collaboration with
11:01Shabbier your and his cancer genetics team.
11:04Advanced endoscopy expertise.
11:05As I'd mentioned,
11:07we are embedding pallative care
11:08in our program and we had a pink
11:11pancreatic cancer early detection
11:12clinic in terms of education.
11:14We are hoping to launch a pancreatic
11:17cancer interest group for trainees and
11:19then in terms of Community wide efforts,
11:22we had a very successful Yale Pack
11:25seminar series this past year under
11:27Research Summit led by Mandor.
11:30In terms of research,
11:3150% of our new pancreas patients
11:34are consented into clinical trials
11:37and we have been the leading in
11:39roller for clinical trials in
11:41the US between 2016 and 2019,
11:44we treated over 400 patients,
11:4638% at care centers from on clinical trials,
11:49and we plan to grow the IIT.
11:58Samples and this represents 61% of
12:00all of our biorepository samples,
12:02so that's a problem for the other diseases
12:05which we will speak to as an opportunity.
12:08And then we also plan on leveraging
12:11innovative multi omics profiling on the
12:13right are some of our recent publications.
12:16The colorectal program is Co led by
12:20doctors Michael Cicchini Shabbier your
12:22and ready in terms of patient care,
12:25we plan on developing a Nurse
12:28Navigator program,
12:29fully integrating genomics with patient
12:31care and developing an early age of onset
12:35colorectal clinic in terms of education,
12:37we hope to work with stakeholders
12:39such as this Milo screening
12:42program on public campaigns.
12:44This is especially pertinent
12:46as the USPS TF guidelines.
12:48Roll out for the lower
12:51colorectal cancer screening age.
12:53And then, in terms of research
12:55for the colorectal program,
12:57we aim to enhance collection of colorectal
13:00specimen in aryel GI BIOREPOSITORY and
13:03increased clinical trial enrollment,
13:05again with IIT's,
13:06and then expand the early age of
13:09onset colorectal cancer thinktank.
13:11This is a committee that was
13:14started by Shawbury Orangel Mamma.
13:18And then Lastly, our community outreach
13:21and engagement plans for colorectal with
13:24developing targeted strategies and special
13:27emphasis on underserved populations.
13:29The advanced hepatic Bilary program
13:31built will link very closely with Mario,
13:34Tresa, Bosco's liver program.
13:36This is being Co led by doctors,
13:39David Madoff, Stacy Stein and Saj
13:41Khan and the Patient Care Education
13:43and research plans are listed here.
13:46I would say importantly for patient care,
13:49we routine tumor profiling for biliary
13:51cancers has proven in recent years to be
13:54critical in terms of therapy selection.
13:57In terms of education,
13:58we will again work.
14:00Mostly within the liver cancer
14:02program and some of the research
14:04plans are very much in line with
14:06the other shared programmatical's.
14:09The neuroendocrine tumor program.
14:10I will be Co leading with Doctor
14:13Darko Pukaar from nuclear medicine
14:15and from a patient care perspective.
14:18We plan on launching a pre PRT clinic.
14:21For those of you who don't know,
14:24PRT is peptide receptor radionuclide therapy.
14:26The agent is 177 Letitia Ndoda Tate
14:29and we plan on doing this to really
14:32streamline and provide some consistency
14:35for heart patients are getting here.
14:38In terms of education,
14:39we also plan on having more
14:42patient events such as Milo,
14:44carers and hopefully in person
14:46and collaborating with some
14:48of our nonprofit foundations.
14:50In terms of research,
14:51the BIOREPOSITORY is also
14:53enriched for nut cases,
14:54and we hope to build on this and then,
14:57in terms of clinical trials,
14:59we have a real opportunity that should be
15:02a key site for impactful clinical trials.
15:05In fact,
15:05we are one of five Centers for a
15:08international clinical trial Meter
15:092 on which I sit on the steering
15:12committee and there are a number
15:15of other novel peptide receptor
15:16radionuclide agents that we hope
15:18to examine in clinical trials.
15:20And we have a number of grants
15:23in the works that will hopefully
15:25start bringing together both Yale
15:28Science and outside science.
15:30Moving on to patient care.
15:33So this data represents new patient visits
15:36from both in the tank and Sir junk.
15:40This does not include radiation
15:42oncology and in our leadership cabinet
15:44meetings we have started reviewing
15:47data and key performance indicators
15:49with the goal to develop a dashboard
15:51of GI cancer specific metrics.
15:53So as you can see here,
15:56this is trends overtime.
15:57We certainly dipped and have really
16:00plateaued since the covid pandemic,
16:02but we have bounced back.
16:11Another interesting set of data
16:13that we looked at it then courtesy
16:16of Kevin Best was our Connecticut
16:18population and distribution of GI
16:20Services across our service area,
16:23and I think this is helpful for us as
16:25we think about developing and placing
16:28services in specific locations.
16:30So as an example here in red
16:33or a GI medical oncology.
16:35Providers in yellow GI radiation oncology.
16:40And in green GI surgical oncology,
16:42so there certainly clustered
16:44at areas of denser population.
16:45Those are in the dark blue,
16:48but I think there are still
16:50certainly some opportunities.
16:52Another data slide that I found also
16:55especially interesting as we think
16:57about sort of strategic planning,
17:00is the incidence of new GI
17:02cancers across the state.
17:04We here look at colon stomach,
17:07Asafa, Geo liver,
17:08and pancreas the the higher rates for
17:12the state are in red and I have kind of
17:16squares around the two disease sites where.
17:20Our rates are higher than the US rates,
17:23and that's true for both
17:25stomach and pancreas,
17:26and I think that's perhaps why we
17:28actually accrue so successfully to
17:30pancreatic cancer clinical trials
17:32and have a very robust clinical and
17:35research program in pancreas cancer.
17:37Would like to also mention you know,
17:40like almost everybody,
17:41covid has disrupted our outpatient practice.
17:44GI Medical Oncology main campus
17:46is still on the 1st floor of
17:48the North Haven Care Center.
17:50I'd like to use this as an opportunity
17:53to really thank my nursing partners
17:56Ali and seller Ooley Hazare PSM,
17:58Kathleen Moseman and Vanna Dest.
18:00We have worked hard to try to
18:03make this space work for our team.
18:06There are still some challenges for sure,
18:09but we're appreciative.
18:10Of some of the small wins that we've had,
18:13such as a new counter space and
18:14putting in a for new workstations.
18:18I'll mention just briefly,
18:20our GI tumor burden multi D efforts,
18:22so as I had mentioned yesterday,
18:25we launched our split of the GI Tumor Board.
18:28This was initiated due to really
18:30incredible growth in our tumor board.
18:32We had really outgrown the existing time
18:35and this is really with credit due to Stacy
18:38sign and more in the lead and others,
18:41and in addition the colorectal team would
18:44like to launch the National Accreditation
18:46Program for Rectal Cancer and in.
18:48Order to do so and become an accredited site.
18:51We are required to have a separate
18:53tumor board so the upper GI pancreas
18:56and net tumor board will be led by
18:58Stacy Stein in the colorectal ****
19:00tumor board is being led by an poncho
19:02and hadn't put out happy and tell.
19:05This is our actually tumor board
19:07from yesterday via zoom.
19:08I'd like to also re late take this
19:10as an opportunity to thank Lauren
19:12Mallette who does an incredible job
19:14with tumor board and the support from
19:16other leaders to make this happen.
19:18It was a little bit more complicated than
19:21I imagined, but to Kevin Billingsley,
19:22hell Terra David.
19:23Fisher, Sonya, Bricelyn tide Wilcox.
19:27Are multi D clinics or a work in
19:30progress and we are building on some
19:32lessons learned from the earlier
19:34colorectal cancer pilot that was done
19:36in North Haven and delayed by Covid.
19:38We have plans for 2 pilots of
19:41colorectal cancer,
19:42multi Dion Trumbull and a pancreas
19:43multi D at main campus and we have
19:46already started some smaller working
19:48groups and are meeting regularly to
19:50try to think about some strategic
19:52planning that that includes some
19:54of the elements listed here such
19:56as enhancing signature of care.
19:58Aligning with our existing disease programs.
20:01Aligning with local expertise
20:02and specialties.
20:03Selecting an optimal location and then later
20:06on we will work on operational topics,
20:09workflow being creative with Tele health,
20:12etc.
20:14Lastly,
20:15in the round with patient care,
20:17I'd like to mention that our team
20:19members make important contributions to
20:21the NCC and panels are institutional,
20:24representative issues,
20:25and Higgins who sits on the NCC
20:27and guidelines steering Committee,
20:29and she's been very helpful,
20:31helpful with guidance around this.
20:33So Stacy Stein serves on the hepatic
20:35biliary piano.
20:36John Kunsman on the pancreas, panel,
20:38Sajc on on the neuroendocrine tumor panel,
20:41Jill Lacey on the Asafa Geo.
20:43Gastric panel in Kim Jong on the small bowel,
20:47colon, rectal,
20:48****.
20:49Channel so let's move on and talk
20:53about education.
20:54I'd like to give two of our fellows
20:56a big shout.
20:58Out papers just gave presentations
20:59last week at our fellow research
21:02retreat and Doctor Timmel Patel
21:03gave a presentation on clinical
21:05outcomes or first line,
21:07full fear and ox versus Gen Plusnet,
21:09paclitaxel in metastatic pancreas.
21:11Cancer Timmel is a senior fellow
21:14will be graduating this year and
21:16has taken a job with the FDA where
21:19he will serve as a medical officer
21:21in the GI Cancer Review team.
21:23So in this study.
21:25Timol and his mentors Gelasia Michael
21:27Cicchini wanted to compare overall
21:30survival and time to treatment.
21:32Discontinuation for two main chemotherapy
21:35regiments from metastatic pancreas.
21:36Cancer folfirinox in gym mat paclitaxel.
21:39They reviewed over 300 patients and found
21:42that patients treated with Firstline
21:44full paradox had increased survival.
21:47These patients were younger and less
21:49likely to be admitted while on treatment
21:53and rates of treatment discontinuation.
21:55Due to toxicity actually similar
21:58between the two regiments.
22:00I'm Secondly, Doctor James Zang is
22:02currently on RT32 training grants.
22:04She has one more year left on that
22:07she presented on her project at MGM
22:10T expression in colorectal cancer,
22:13the immune microenvironment in
22:14response to DNA damaging agents.
22:16Her mentors are Doctor Kurt Shelper,
22:19Michael Cicchini and Jill Lacey,
22:21and her specific aims and I will not go
22:24into all of the details on her project,
22:28which are were beautifully presented by her.
22:31At the specific aims are to quantify
22:33MGMT expression in colorectal cancer
22:35cohorts and assess Association of MGMT
22:38expression with DNA damage repair,
22:41adaptive tumor, immune response,
22:43and overall survival,
22:44and then Secondly review some of these
22:47same characteristics in an investigator
22:49initiated clinical trial launched
22:51by Doctor Cicchini and Tamil Patel
22:54using tamazula, my dental lab rib.
22:57So very exciting.
22:59In the realm of patient education,
23:02we tested out the Smilow shares platform,
23:04which was actually very user
23:06friendly and lots of fun during
23:08colorectal Cancer Awareness Month.
23:10In March we gave two separate presentations,
23:12one to the New Haven community and
23:15the other to the Greenwich Community,
23:17and we took advantage of again local
23:20expertise, particularly in Greenwich.
23:21We collaborated with one of the
23:24colorectal surgeons at Greenwich
23:25Hospital and two of our Care center,
23:28medical oncologists,
23:28Doctor Lee and Doctor.
23:32So moving on to clinical research.
23:35So how does the GI DART clinical trial
23:38portfolio compare internally and again?
23:40These are metrics that we are looking
23:42at in the course of our leadership
23:45cabinet discussions. A thank you.
23:48Great thank you to Christina Weishar CTM.
23:50So the GI DART clinical trial portfolio is
23:548% of YCS overall clinical trial portfolio,
23:56yet it represents actually 11% of
23:59all the clinical trial accruals.
24:01We have proved quite well.
24:03And 14% of analytic cases indicating
24:06that we could potentially do better.
24:085% of the GI cancer analytic case
24:11volume accrues to clinical trials,
24:14so we are higher than the national benchmark.
24:17However, the NCI expectation is as much as
24:2120%, so for sure it opportunity to do better,
24:25or GI DART sponsor mix is as follows.
24:2844% industry, 39% NCI, and 17% IIT.
24:31The ideal is thought to be a third,
24:34a third a third, so we certainly
24:37would like to increase our IIT.
24:39Portfolio.
24:41Our accrual trends follow the overall
24:44YCC accrual trends with a dip during
24:47covid and we are now starting to recover
24:50and our accrual over the last 12 months
24:53has been heavily reliant on cooperative
24:55group studies and industry studies.
24:57And note that the numbers on this slide
25:00represent trials managed by the GI Dark,
25:03but we have a number of patients
25:05that go on to other other darts,
25:08such as phase one.
25:12We are grateful and very relyant
25:14on our care center colleagues for
25:17accrual to our clinical trials.
25:19In fact,
25:2038% of our clinical trial accruals came
25:23from our care centers between 2016 and 2019.
25:29I'd like to highlight two of our
25:32investigator initiated clinical trials that
25:34first here is pidd by Doctor Jill Lacey.
25:36It's a phase two study of PERI
25:39operative modified folfirinox
25:40and localized pancreas cancer.
25:42It's a single arm study in which
25:44patients receive 6 cycles of modified
25:46folfirinox followed by surgery followed
25:48by 6 more cycles of modified folfirinox.
25:51This is actually one patient
25:53away from completing enrollment,
25:55so we're very excited about
25:57that and I think that.
25:59There will be some very interesting
26:02correlative's that come along with this.
26:05Doctor Kim Jong is leading another
26:08investigator initiated trial,
26:09a phase two study to evaluate modified
26:13folfirinox and stereotactic body radiation
26:16and nonmetastatic unrespectable key back.
26:19In this study, patients received up
26:21front fulfi Rannoch 6 to 12 cycles,
26:24followed by SPRT, followed by surgery.
26:28There are a number of really.
26:32It's a very interesting correlative's
26:34that are multi disciplinary including
26:37US elastography with doctors Farallones
26:40leniency T DNA with Doctor Patel,
26:43molecular and immune future
26:45assessment with doctors.
26:47Cikini Joshi Farallon Sklar
26:49and development of pancreatic
26:51organoids instructor Joshi.
26:58I also would like to really give
27:00some kudos to Doctor Michael Cicchini
27:03who has just received his KO 8,
27:06so this is really a beautiful combination
27:08of the clinical and translational research.
27:11So the title of his Kaylie does DNA
27:14damage as a tool to enhance the
27:17immunogenicity of cold GI tumors.
27:19His mentorship committee is listed here.
27:21His aims in his K-8.
27:23I'll just read them and won't
27:25go into the details.
27:27But it is to perform clinical
27:29trials with novel combinations of
27:31DNA damaging agents for patients
27:33with MGMT promoter hypomethylated
27:35colorectal cancer to identify
27:37predictive biomarkers for novel
27:39alculator combinations in CRC and Tour desk,
27:43assess DNA damage is a tool to enhance the
27:47immunogenicity of cold colorectal tumors.
27:51I'd like to end with a couple of
27:54new projects that we're working on.
27:56This one is actually very exciting and
27:58I'll give a little bit of a teaser and
28:01I think Roy and add Captain and I are
28:04talking about finding another forum,
28:06but we are working on a clinical
28:08trial matching project in GI oncology
28:10with Guangdong and Wade Schultz and
28:12a team to really determine if we
28:14can match patients to the clinical
28:16trial at the right time,
28:18accurately efficiently with high
28:20volume in a project that's scalable.
28:22Other team members included Kathy and
28:24Christina Weiss, myself in your fish back.
28:28We are using this clinical trial on
28:31its Michael Cicchini is tamazula.
28:33My dental lab rib study.
28:35As a pilot we've selected for inclusion
28:38criteria in which Gwen and Wade and their
28:41team use natural language processing
28:43and structuring data from the EMR.
28:46This is the workflow focus on the orange
28:49box and we are using the entry event in the
28:53pre screening event as pilots right now.
28:56Just to give you a sense of the numbers,
28:59we that blue top line looks at the number
29:02of visits to GI Oncology Department by
29:04week followed by the number of patients
29:06unique patients to GI oncology by week,
29:09then down in Gray.
29:10The number of patients with colorectal cancer
29:12than those with metastatic stage four,
29:14and then ultimately that bottom
29:16line where you see the numbers in
29:18red range from 10 to 15 patients
29:20per week that could potentially be
29:22eligible for this clinical trial.
29:24How great would it be if
29:26you got in your inbox?
29:27A list of eligible patients every
29:30week for your individual trials.
29:32So this pilot was incredibly
29:34effective and efficient.
29:35It had about a 98% accuracy rate and it
29:38really cut down on the amount of time.
29:42So before we estimated 3.11 minutes
29:44per chart for 10 week full time
29:46working hours and afterwards 1.82
29:49minutes per chart which just equals
29:51three days of full time working hours.
29:54So I'm really excited to see
29:57where where this goes.
29:59Lastly,
30:00Aryel GI tumor biorepository is a
30:02real foundation for our program.
30:04This is being PII by by Doctor John,
30:07Councilman and the technician Joanna,
30:09who it's been in existence since
30:122012 and we have over 1100 patients,
30:15but it certainly has, like many things,
30:17taken a bit of a hit during covid.
30:21John has really taken this as an
30:23opportunity to revamp and modernize,
30:25so our accrual numbers have certainly
30:28increased overtime or biorepository.
30:29Is over represented with colon,
30:32rectal and pancreas tumors.
30:34We certainly hope to expand on this.
30:38And as I'd mentioned,
30:39John really has revamped the infrastructure,
30:42so we have an existing steering committee,
30:44but we now actually have a new
30:47location and BML.
30:48We have a brand new freezer and
30:50John has completely overhauled the
30:52consent and intake process to reduce
30:55the survey link for patients and to
30:57add explicit language for modern
30:59research activities such as multi
31:01omics cell lines and organoids
31:03and deposition of anonymized
31:04data in the public repository's.
31:06And we have a number of examples of active.
31:10Projects including a study in pydoc
31:12with UCLA and then Elappara Bram study
31:14on this multi institution study.
31:16So we have a number of future needs,
31:19including more,
31:20broader and more diverse tumor collection,
31:22resumption of specimen collection in
31:24our care centers and updating our database.
31:27I'm going to just end with a mention
31:29of some really exciting work that Wade
31:32Schultz and his team are doing to use
31:35a computational health platform to
31:37build an integrated clinical database.
31:39So imagine.
31:40That you have all of your structured
31:43E HR data, imaging, pathology,
31:45genetics, all of these data sources.
31:48You put it into a funnel and this
31:51is a essentially a workflow you
31:53can create curated data by the use
31:56of red cap and then Wade and his
31:59team create aid and integrated user
32:02interface so that it really minimizes
32:05redundancy of manual data entry.
32:07The CHP news cases include COVID-19,
32:10in which they were.
32:12The teams were quite prolific.
32:14Hematology is just starting to launch
32:17this and integrating a number of key
32:20structured databases including C,
32:23Bioportal,
32:23Redcap omaf genomic data in registry data.
32:28So to end, you know,
32:30I think that we have a number of strengths.
32:33We have a high patient volume
32:35within our network.
32:36We have a large clinical trial and
32:38financially healthy portfolio.
32:39Still that we're hoping to maintain.
32:42We have an existing and expanding
32:44biorepository and strong basic
32:45and translational science.
32:46I think we have a lot of opportunities
32:49in the next one to five years,
32:52including expanding our clinical
32:53trial portfolio with IIT's.
32:54I think really investing
32:56and expanding and the.
32:57Biorepository,
32:58I think that will help us help
33:00lead us to better team science and
33:03then in the long term or medium
33:05term goals of obtaining multipy
33:07and program project funding.
33:09So I will stop there.
33:12And pass the baton to Amanda,
33:14and then we'll take questions after right?
33:16Thanks, Pam. I think we should
33:18move on to Amanda and then
33:20we'll do questions at the end.
33:22Please put your questions in the chat.
33:24I know I have a few for you,
33:27but now we're very fortunate to have.
33:29Mandar was Amdar who is assistant
33:30professor of genetics and Medicine.
33:32He's part of the Yale
33:34Cancer Biology Institute,
33:34threes at West Campus,
33:36and my Dream is one day will hold one of
33:39our grand rounds in person on West Campus.
33:41I promised that tomorrow I'm
33:43in many years ago.
33:44We will hold to that scientific director
33:46of the Center for Gastrointestinal
33:48Cancers here at the hospital
33:50and just quickly his background.
33:53He's also has a Stanford background
33:55medical degree from Stanford
33:57and then internship residency at
33:58some small Hospital in Boston,
34:00Brigham and Women's Hospital,
34:02Dana Farber Cancer Institute.
34:03And then he completed his postdoctoral
34:06research at the Koch Institute of
34:08Integrative Cancer Research at MIT,
34:10so a lot more I can say about manager,
34:14but I will.
34:15Let you hear about his work, and I'm Amanda.
34:17The floor is yours.
34:19Great thank you Roy for
34:21the kind introduction.
34:22I just want to build on what Doctor
34:24Kunz is described and talk a little
34:27bit more about up challenges and
34:29opportunities in translational research,
34:31specifically in GI cancers at Yale.
34:33So I'll briefly discuss some more
34:36detailed metrics on the current
34:37state of GI Cancer Research at Yale
34:40and then talk about some of our
34:42goals in building translational
34:44Sciences within the center.
34:45Describing four specific
34:46overarching initiatives.
34:47Distance shown here and then,
34:49talk a few.
34:50A bit about some of the more specific
34:52initiatives that we have planned
34:53using pancreatic cancer and the
34:55Yale Pancreatic Cancer Collaborative
34:57is an example of the types of
34:59things that we're hoping for.
35:01So I'd like to start by saying that
35:04GI Cancer Research at Yale within
35:06the Cancer Center is prolific,
35:09high impact and inclusive.
35:10Shown here are data from the Cancer
35:13Center GI cancer related publications
35:15over an 18 month types time span.
35:18From July 2019 to December 2020,
35:21and as you can see,
35:23there were more than 130 publications
35:25for GI cancer related research
35:27within this 18 month time span,
35:29amounting to about 7.5 publications
35:31per month,
35:32which I personally thought was
35:34quite impressive given that many
35:36of our investigators were dealing
35:38with the pandemic during this time.
35:40Importantly,
35:41more than 1/4 of these publications,
35:43four published in high impact journals,
35:45and they represented the full
35:47spectrum of diseases within.
35:49The GI space, including pancreatic cancers,
35:52colorectal and **** cancers,
35:54gastroesophageal liver cancers.
35:55Furthermore,
35:56these publications included 47
35:58individual investigators within
35:59the Cancer Center.
36:01Again,
36:01quite a diverse crew including
36:04basic scientists,
36:05clinical and translational scientists,
36:07and epidemiologists.
36:08Now the story is very similar for
36:11active research funding where the GI
36:14cancer portfolio includes nearly $5
36:17million in direct costs of research funding.
36:21This is about 2/3 in peer reviewed.
36:24Either NIH or competitive foundation grants.
36:27And the remaining from industry or
36:30non peer reviewed foundation grants.
36:32You can see there is a heavy influx
36:34of money focused on pancreatic cancer,
36:37but there is a good spread across
36:40the different disease programs.
36:42Additionally,
36:42this funding has been accumulated by
36:4524 independent investigators with
36:47a very similar spread in the basic
36:49clinical translational epidemiologic space.
36:51Importantly, most of these funding sources,
36:53in fact, the vast majority,
36:55are really independent grants,
36:57single investigators,
36:58and so the hope is to really love
37:01leverage this great breath.
37:03Of scientific expertise,
37:04clinical care,
37:05and clinical research expertise
37:06and try and build and synergize
37:08their efforts into teams,
37:09and that's sort of the major goal
37:11of where we're going to go with
37:14the GI Cancer Center.
37:15So again,
37:16one of our major goals is to build
37:18across display research teams
37:20that bring together clinical,
37:22translational,
37:23basic and population health scientists.
37:25With the plan to allow these teams
37:27to enable team based research grants
37:29including multi P IR ones, PO1.
37:32Since for grants to try and grow
37:34investigator initiated trials
37:35based on yell science Doctor Kunz,
37:37allude to the fact that less than 20%
37:40of our current grants are
37:42investigator initiated would like
37:44to bump that up to at least a
37:46third if not a half really showing.
37:48Sort of the importance of science
37:50within Yale and and what can result
37:53in terms of translational care.
37:55And finally, we'd like to use
37:57these teams to inspire trainees
37:59towards the Korean translational.
38:01She, like Cancer Research Doctor
38:02Kunz highlighted several of our
38:04trainings doing trainees doing really
38:06exciting science within this space.
38:08We like to to recruit even more
38:10to really further the mission.
38:12And Jack answers.
38:13Ultimately,
38:14the goal is to make Yale's destination
38:16Center for GI cancers such that
38:18Yale is synonymous for outstanding,
38:20not only clinical care,
38:22but also homegrown science.
38:23That translates to the clinic.
38:26Now there are number of challenges
38:28that get in the way of boosting
38:31translational science in GI cancers.
38:33Indeed,
38:33these are challenges that Roy could
38:35speak to for thoracic or even other cancers,
38:38and also challenges that exist
38:40across the academic spectrum,
38:42and these include a lack of time
38:44or lack of institutional resources,
38:46a lack of knowledge or expertise,
38:49or even awareness of potential
38:50collaborators within the institution.
38:52And as team based science is increasing.
38:55Ensuring adequate recognition or
38:58opportunities for career advancement.
39:00So in terms of overarching initiatives
39:02to combat these particular challenges,
39:04we've come up with four.
39:06One is to really emphasize
39:08community building,
39:09which is hopefully to bring awareness
39:11of potential collaborators,
39:13enhance the community knowledge
39:14and expertise,
39:15and that can be leveraged towards
39:17team based grants.
39:18Additionally,
39:19try to enhance research education
39:21across spectrum to try and get
39:23basic scientists to communicate
39:25with clinical scientists and vice
39:27versa to enhance knowledge and
39:29to bring together teams.
39:30The third pillar is to develop resources
39:33that's both financial in terms of
39:35grants and funding pilot funding,
39:37but also institutional resources for
39:39tissue resources such as bio banks
39:42that are hard to come by and hard
39:44to leverage within individual labs.
39:46And finally,
39:47we like to take advantage of these
39:49great developments and disseminate
39:51it to the Community using web based
39:54or social media platforms as an
39:56opportunity not only to tell everyone
39:58what a great place Yale is for GI
40:01Cancer Research and clinical care.
40:03But also potentially to recruit outside
40:06funding to support some of these others.
40:09So to start to chip away and sort
40:12of build some of these pillars,
40:14a group of us started the yellow
40:17Pancreatic cancer collaborative
40:19or yellow pack.
40:20Shown here is the steering committee
40:22that includes Mary leaders in
40:24pancreatic Cancer Research and
40:26clinical care across different
40:27divisions and departments.
40:29Including medical oncology,
40:30radiation oncology surgical oncology,
40:32gastroenterology,
40:32pathology and the basic Sciences.
40:34We formed the Yale Pack,
40:36which is an inclusive team of physicians,
40:39scientists and trainings that seeks
40:41to synergise the strengths of the
40:43L science and clinical expertise
40:45to accelerate transformative
40:47research and pancreatic cancer
40:48to sort of nucleates the LPK,
40:50we held a summit for Community
40:53building last August.
40:55This was a entirely virtual
40:57summit that included more than
40:59130 participants. Importantly,
41:01more than a third of whom were trainees
41:04in participation included 16 different
41:06departments and three institutes.
41:09We had 16 different speakers who either
41:12were actively pursuing pancreatic
41:13Cancer Research initiatives or those
41:16shown in red had not prior previously
41:19been involved in pancreatic Cancer
41:21Research to highlight existing research,
41:24as well as to engage.
41:26Scientists with innovative technologies
41:27that could be applied to this research
41:30space and through these efforts,
41:32we've been able to actually
41:34generate some teams.
41:35I'll describe a few here of examples of
41:38multidisciplinary teams in GI cancers,
41:39one of which is involves our own lab
41:42in collaboration with the key being
41:44endocrinology and submit the Krishnaswamy
41:46in genetics and computer science,
41:48in which we have been studying and
41:51identifying a novel intra pancreatic
41:52endocrine exocrine hormonal
41:54signaling axis that is a driver.
41:56Pancreatic ductal and questionable
41:59progression in obesity.
42:01Luisa Escobar hires in radiation therapy,
42:03has partnered with Jeff Townsend by
42:06Statistics John Chrisman and Surgery
42:08and Nick Joe Sheehan immunology to
42:10understand RNA splicing and tumors,
42:12adaptation and a tumor immunity building
42:15off really seminal science from the
42:18Escobar Hoyos slab that identified a
42:20novel role for Mutant P 53 and splicing
42:23regulation and pancreatic cancer.
42:25Both of these teams based grants have
42:28been recently funded by the Damon
42:30Runyon Rachleff Innovation Award,
42:31highlighting that these team based
42:34approaches are really well received by
42:37funding organizations in the NCI alike.
42:40The Teen Challenge awards that have been
42:42pioneered by the Cancer Center have also
42:45funded several GI cancer related teams.
42:47I'll highlight two of them here.
42:50This one,
42:50led by set hers on in chemistry that
42:52tries to examine the molecular cancer
42:55microbiology and the underpinnings of
42:57microbiome associated carcinogenesis.
42:59Building on work from South Arizona
43:01and collaborator Jason Crawford
43:02on synthesizing the Genotoxin.
43:04Cali Bactine,
43:05which is thought to be an inducer
43:07of colorectal cancer.
43:09And leveraging this kind of seminal
43:12pre pre clinical work to understand
43:15pathogenesis by which microbiomes promote
43:18cancer in particular colorectal cancer.
43:21And another grant funded by the Teen
43:23Challenge Award is includes Auto Group
43:26in collaboration with John Wessel,
43:27Mirsky,
43:28Anne Rd,
43:28Hoffer and Comparative Medicine
43:30which seeks to define the effects of
43:32dietary fatty acids on breast cancer
43:34and pancreatic cancer progression,
43:36leveraging innovative high fat diets
43:38than Metro diapers group has developed
43:40that represented the diversity of bias
43:42found in human cancers and trying to
43:44identify effects on host Physiology as
43:46well as on tumor progression and you
43:49can see there's a diversity of effects.
43:51On pancreatic cancer progression
43:53using these diets.
43:55Beyond building teams,
43:56we've also been interested in
43:59educating these teams on the latest
44:02and greatest advances and basic
44:04science and clinical and translational
44:06science by forming the Yale Pancreatic
44:09Cancer Collaborative Seminars series.
44:11This included an outstanding cadre
44:13of investigators,
44:14principally outside of Yale,
44:16who encompass that Breath of basic
44:19two clinical science,
44:20as shown here,
44:22and was an opportunity for our
44:25community to learn about.
44:27The advances in pancreatic
44:28Cancer Research and care,
44:29and to try and build upon some of
44:32what has already come before us and
44:34really understand the unmet needs in
44:36this space and how Yale could position
44:39itself to meet these particular needs.
44:42Another core initiative for our group is
44:45to really build resource development.
44:47Doctor Kunz highlighted the GI cancer
44:50Biobank, which is actually quite prolific,
44:52includes a large number of samples in the
44:55pancreatic cancer and codirector cancer,
44:57and specifically and beyond.
44:59Expanding this to other cancers
45:01in the GI space.
45:02We've also been working closely with
45:05their collaborators in surgery,
45:07Yelp, Pathology,
45:07and Lab Medicine to develop new
45:10living cancer models.
45:11Based on these perspective collection
45:14of samples.
45:15These include patient drives into
45:17graphs and patient derived organoids
45:19with the hope of developing and
45:21molecularly characterizing some
45:22of these very precious tissues.
45:24Now importantly,
45:25many of these tissues are quite limited,
45:27particularly in diseases like
45:29pancreatic cancer,
45:30where the tumor fraction is quite low,
45:32and so we need to be able to leverage
45:35emerging technologies that are able to
45:38garner a large quantity of information
45:40from small and scare samples.
45:43Answer To that end,
45:44our collaborative has tried to bring
45:46together innovative scientists such
45:48as Stephen weighing in genetics
45:50and wrong thing and biomedical
45:52engineering who developed interesting
45:54multi omics technologies that allow
45:56spatial analysis of gene expression,
45:59protein expression and even 3D
46:01genome organization in very scarce
46:03tissue based samples.
46:04And so we're excited of the possibility
46:07of taking advantage of the Bio Bank to
46:10do deep molecular characterization to
46:12build resources that could be leveraged.
46:15Or to address particular questions
46:18that our investigators might have.
46:20And finally,
46:20I think it's important for us to be able
46:23to expand and let the community know
46:26about our translational science efforts.
46:28Shown here are the breakthroughs
46:30magazine this year that highlighted
46:32the team building that we've done
46:34in the pancreatic cancer space.
46:36And shown here also is the ability
46:38to use Twitter to really expand our
46:40reach of our center and in hopes
46:42of not only educating the community
46:45but also potentially as a fund
46:47raising mechanism in the future.
46:49So what are some of the future
46:51specific plans we have in mind
46:53to meet these initiatives?
46:54One is we like to expand the
46:56activities we've done in pancreatic
46:58cancer to the other centers to focus
47:00on community building through a
47:02similar types of summits or seminar
47:04series across our core programs.
47:07We'd also like to develop some cross
47:09program initiatives within the center.
47:11Importantly,
47:11we want to focus on physician
47:13scientist recruitment in GI cancers.
47:15I think they serve as.
47:22And in the center from Michael
47:24Instagram Cology, which is actively
47:26pursuing junior physician scientists,
47:28recruits and we hope to be able to bring in
47:32more who have a real focus in GI cancers.
47:36We also want to try and bridge the gap
47:38between basic and clinical scientists,
47:40and to do that, we're going to try
47:43and launch the doctors in series.
47:45This is a series to allow clinicians to
47:48educate basic researchers on the diagnosis,
47:50treatment, and importantly, the unmet needs.
47:52For specific answers only.
47:53This will these be important
47:55community building events,
47:56but also an opportunity to educate
47:58our basic science community on the
48:01challenges faced in the clinic.
48:03We want to include basic and translational
48:05research talks into the CME events within
48:08our community that Doctor Kunz described
48:10again as an education initiative,
48:12but also an opportunity for outreach.
48:16We want to facilitate team
48:17based grant funding,
48:18in particular trying to take advantage
48:21of internal support such as TCA.
48:22The team challenge awarded the
48:24teacher grants and ultimately to
48:26direct these teams and support these
48:28teams administratively towards
48:29developing or program project grants.
48:31Just peel ones and spores we want
48:33to increase Accessibility in Electro
48:35characterization of biobank samples.
48:36Doctor Kunz describe some events,
48:38some initiatives in the computational side.
48:40We also want to leverage some
48:42of the multi omics technologies.
48:44And finally we want to fundraise
48:46towards the center and disease
48:47programs to support this translation.
48:49Research clearly to be able to build these
48:52teams and provide private pilot funding.
48:54Some amount of philanthropy
48:55is going to be required.
48:58And to do that we want to create
49:00a unified Twitter and website
49:01presence to really unify the center,
49:03but also to make key announcements
49:06of advances in translational
49:07science within our center.
49:09And so with that,
49:10we're happy to take any questions.
49:14Thank you both.
49:15That was absolutely wonderful. Well,
49:16we'll put some some questions in the chat,
49:19so maybe I'll start, you know,
49:21for you, Pam can you speak a
49:23little bit about you talked about
49:25screening for colorectal cancer?
49:27Can you talk about what the
49:29current guidelines are and how
49:30we're addressing that here?
49:32At? Yes, my own.
49:33Also, the whole HealthEquity
49:34issue around this.
49:35How are you making sure that all
49:38patients are getting in for a screening?
49:42So, so at present the recommended
49:44screening age is still 50
49:46on the USPS TF guidelines.
49:47The draft has not been accepted
49:49into practice just yet.
49:51So what I will say,
49:52I have an in since my husband is a
49:55gastroenterologist in the community,
49:57but he has said that I think this
49:59is appropriate that we recommend
50:01that if patients who are between
50:03the ages of 45 and 40 niner
50:05interested that they check with
50:07their insurance company first.
50:08I mean, I anticipate that this will
50:11in fact be adopted and then we will.
50:14Have a considerable education to do
50:16and I think that partnering with
50:18shabbier your and this the colorectal
50:21cancer program Shabbir died and his team.
50:23We talked a lot about outreach
50:25and and how we can improve our
50:28efforts in that space.
50:31Right, you mentioned you're
50:32using Wades database.
50:33Are you able to look through
50:34that database by the patients
50:35that you're screening,
50:37representing the Community in general,
50:38or their areas to enhance?
50:41So we are just starting working with Wade,
50:44but that's an excellent idea and I
50:46think ways that we can leverage that
50:48and also with with Marcelonis Smith.
50:52Amanda, why is pancreatic cancer
50:54so difficult to to treat?
50:56You know, you have these new these
50:58new approaches, but immunotherapy.
50:59It doesn't seem to work as well there
51:02as in many of the other cancers.
51:04What's the reason for that?
51:07Yeah, I think there's a number of kind
51:10of unique features of pancreatic cancer,
51:12in particular that make it
51:14particularly challenging for
51:16therapeutics and even therapy space.
51:17It's well known that pancreatic
51:19cancer has a quite a bit of a
51:22different stromal microenvironment.
51:24In particular, it's thought
51:25that this micro environment made
51:27up of fibroblast immune cells,
51:29like macrophages in particular,
51:30as well as exercising matrix proteins,
51:33can be quite immunosuppressive,
51:34and even in mismatch repair deficient.
51:37Pancreatic cancer is the response.
51:38Rates are quite a bit lower than,
51:41for example,
51:42what we'd see in colorectal cancer,
51:44suggesting that there's something
51:45unique about the intrinsic
51:47biology of pancreatic cancer,
51:48and I think the stroma quite
51:50plays quite a bit of a role.
51:53Importantly, pancreatic cancer
51:54is genetically fairly bland.
51:55It gets 4 hallmark recurrent
51:57genetic alterations,
51:58in particular in the proto oncogene carass,
52:00and three other tumor suppressor genes.
52:03So in terms of targetable
52:04genetic alterations,
52:05there are few.
52:06And even within care as mutations
52:08there currently targetable
52:091G12C mutations are quite rare,
52:11only found by two to 3% in our own
52:14data suggested that even if you
52:16had a perfect chaos inhibitor,
52:18resistance is likely to emerge
52:19at least half of the cases,
52:21and so I think there are a number
52:23of factors that lead to the poor
52:26outcomes of pancreatic cancer,
52:27and I think one aspect that deserves
52:30more attention is prevention in the disease.
52:33One of the one of the key factors
52:35to poor outcomes is often late
52:37stage of diagnosis,
52:39where more than 80% of patients
52:40are found at a time when they're
52:42not surgically resectable,
52:44which really is the mainstay
52:45curative option in this disease,
52:47and So what can we do to understand
52:49when this disease emerges?
52:51Can we intervene earlier?
52:52Can we identify earlier disease,
52:54and can we even develop strategies for
52:56prevention by understanding risk factors?
52:57For example, how they play a role,
53:00and that's sort of driven some of
53:02our own efforts in the obesity.
53:04Pancreatic cancer space.
53:07Other genetic risks as well and I
53:09have to use big data AI approaches.
53:11Do you think we'd find some some genomic
53:14factors that might tell us who might need
53:17need to be screened earlier?
53:19Yeah, there are a number of genetic
53:21factors that have been identified
53:23only about 10% of pancreatic cancers
53:25are thought to be familial in nature,
53:27and a subset of those patients will
53:30have known genetic alterations
53:31and our screening clinic here.
53:33Led by James Farrell,
53:34is focused on that in trying to.
53:37Follow these familial cases
53:38not only in terms of genetics,
53:40but also to understand other risk
53:42factors such as new onset diabetes.
53:45And it turns out about 1% of
53:47pancreatic cancer cases can be
53:49identified when you want to diabetes.
53:51Could we use that as a biomarker
53:53of sort of early detection?
53:55And so there are a number of
53:57avenues that people are exploring,
53:59and certainly big data type
54:01approaches that mirror that match.
54:03Clinical prior clinical history
54:04to pancreatic cancer developments
54:06again may be taking advantage of.
54:09EMR mining, like Wade Schultz is doing,
54:11could help identify some of those
54:13patients and identify other risk
54:15factors and their number of groups,
54:17including the Dana Farber Group
54:19that is trying to build risk scores.
54:21That combined with genetics as
54:23well as non genetic factors to
54:25truly determine who are perhaps
54:27the most highest risk.
54:28And finally,
54:29I think we still need to further optimize.
54:32What are the best screening protocols?
54:34Is it a combination of
54:35endoscopic ultrasound imaging,
54:36blood based biomarkers?
54:37All of those are active areas investigation.
54:40We have a few questions,
54:42so Pam, you're very modest.
54:43I actually, I'm waiting to see how
54:45you do the GI program and I'm at
54:47all the long program after you you
54:49just fantastic and I have to just
54:51compliment you coming here during
54:53this very difficult year and telling
54:55this amazing group together between
54:56the campuses and I just think it's
54:58remarkable and I guess zoom has helped
55:00a little bit but hopefully at some
55:02point we'll see each other in person.
55:04But how do you clinically with care
55:06on going at 15 different care centers?
55:08And I was impressed by that
55:10picture where you actually.
55:11All the different people,
55:12how are you putting practice plans in
55:15place and knowing that someone who
55:16goes to North Haven versus someone that
55:18goes to Greenwich or Main campus is
55:21getting the same sort of approach and
55:23and care for one of these diseases?
55:27That that's a great question.
55:28You know, I'd say that the first step
55:31has been creating forums where our
55:33team members will get together and
55:35I have to say that we've had just
55:38really tremendous virtual attendance,
55:39and I think that's one silver lining
55:42of the zoom format is that we have no
55:4430 to 40 people attending tumor board,
55:47averaging 40 patients attending
55:48our seminar series,
55:49and those that's really community building.
55:51I think Mandar spoke to that as well,
55:54and I think as soon as we have
55:56that as a foundation,
55:58it creates other opportunities
55:59for collaboration.
56:00I'm Julie, she is our Director of Education
56:03in our leadership cabinet and I know that.
56:07She's told me this,
56:08but I think I can say this,
56:11but I think she's she and I and the
56:13team are really eager to work on
56:15that signature of Karen and talking.
56:18That's why we have Journal clubs.
56:19We talk about standard practices very
56:21openly with all of our team members,
56:23and we have really tremendous.
56:26Dissipation from our care center
56:28members and you know,
56:29I think that's helped by Jeremy Corbyn's.
56:31Key really being an integral
56:33part of our team.
56:34He has been for a long time and I think
56:36infusing his role that's helping as well.
56:41Absolutely,
56:41I would just at the end of the hour.
56:43Any other questions or comments?
56:45One thing I'll ask you mentioned it.
56:47You make sure Lacey ask both of you.
56:49I see a lot of fellows on the line.
56:51One of the one of the groups is fellows room,
56:54so I guess there hopefully
56:55had getting a solution there.
56:57If not, let me know for next week,
56:59but the question is,
57:00do you have projects you know our
57:02fellows and we have great fellows?
57:04Medical students might even be
57:05some undergraduates listening.
57:06I don't any one of their projects.
57:08How it's one find a project
57:09in GI cancer Mandar.
57:10If they wanted to work in the lab
57:12or between a lab in the clinic,
57:13or Pam in the clinic,
57:14can you let us know?
57:17Yeah, I think one of our goals
57:18is to make very accessible shovel
57:20ready projects for people with
57:22limited time medical students,
57:24residents, fellows and I think
57:25there are a couple of advantages.
57:27The one is the biobank
57:29which is quite expensive,
57:30particularly in again pancreatic
57:32cancer and colorectal cancer that
57:33might allow tissue based analysis
57:35that might be more efficient.
57:37The second is we have a
57:39large number of patients,
57:40particularly the pancreatic cancer space,
57:42that we followed for many years,
57:44and so some of this studies,
57:45for example, what?
57:46Doctor Patel has done is based
57:48on those types of retrospective
57:50analysis and this clinical database
57:53that we have in GI cancers.
57:54And so again those types of
57:57projects are probably much more
57:59numerous and we need to make
58:01those clearer and make them more
58:03shovel ready so that we can get
58:05our trainees involved quickly.
58:08In any any further I'll just yeah,
58:10I'll if I can just add right,
58:12you know we had our one of our
58:15programs director's meetings last
58:16week and we as a those four programs,
58:18all the code leaders identified as
58:20our next top priority doing just
58:22that of really developing this list
58:24as we have new trainees coming in
58:26in July and having that available.
58:29Right, and you guys are great.
58:31Actually one big part of
58:32the shovel is the handle,
58:33which is the mentor ship and on these
58:35projects you don't want to have a good idea,
58:37but you know it's I can tell you
58:39from my own career it's having
58:40mentors and people that help you
58:42so I can see you have that.
58:44And plenty of that in the GI Group will
58:46look forward to having you back in six
58:47months or so to hear more progress,
58:49maybe bring some other members of the group,
58:51but this is been a fantastic
58:53grand rounds today.
58:53Will look forward to your first grand
58:55rounds for the GI program with an invited
58:57guest from Puerto Rico in two weeks and.
58:59Thank you all.
59:00Thanks everyone for coming today
59:02and we'll see you back next week
59:04for Cancer Center grand rounds.
59:05Thank you.
59:06Pam, Amanda.
59:07Thank you, thanks.