The Yale Center for GI Cancers: Challenges and Opportunities

Transcript

• 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.