Smilow Shares: World Pancreatic Cancer Day

November 19, 2021

Information

November 18, 2021

Presentations by: Drs. Mandar Muzumdar, Jill Lacy, James Farrell, Laura Baum, and Ronald Salem

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00:00Good evening, my name is modernism.
00:02Darren, a medical oncologist and
00:04scientific director for the Center
00:05for Gastrointestinal Cancers.
00:07It's Milo Cancer Hospital
00:08in the Yale Cancer Center.
00:10I'm delighted to welcome you to
00:12our smaller shares event tonight
00:13centered on new treatment advances
00:15and innovations in pancreatic cancer.
00:18We're honored to bring this
00:19program to you today to commemorate
00:20world Pancreatic Cancer Day.
00:22Joining a coalition of nearly 100
00:25patient advocacy organizations
00:26originating in more than 40
00:28countries across six continents to
00:30raise awareness for this disease.
00:32There is no question that pancreatic
00:34cancer is a great challenge,
00:35though fortunately it remains
00:37a relatively uncommon cancer.
00:39It is anticipated that one in 64
00:40people will be diagnosed with
00:42pancreatic cancer in their lifetime.
00:44The disease currently stands as the
00:4610th most common cause of cancer
00:48in men and the eighth most common
00:49in women in the United States.
00:51In contrast,
00:52pancreatic cancer is the fourth
00:53most common cause of cancer related
00:55deaths in both men and women,
00:56and is expected to rise to the second
00:59overall within the next decade.
01:01Despite these statistics,
01:02there are a number of reasons for optimism.
01:04First,
01:05the last decade has brought multiple
01:07innovations in medical and surgical
01:08treatment that is significantly moved.
01:10The needle on overall outcomes.
01:12Second research,
01:13including from labs here at Yale,
01:16has provided greater knowledge of the
01:18basic biology of pancreatic cancer,
01:20which is informing new treatment strategies.
01:22Third,
01:22the discovery of both genetic and non
01:25genetic risk factors has helped us
01:27better identified those at highest
01:29risk of developing pancreatic cancer.
01:31And to formulate new approaches for
01:33screening and early detection and
01:35finally changes in care delivery
01:37models towards team based,
01:39multidisciplinary,
01:39personalized and holistic care
01:41is leading to improved outcomes
01:44and quality of life for patients.
01:46Tonight you will hear about these
01:48medical and surgical advances,
01:49risk factors and screening methods
01:51and team based holistic care from
01:53key experts in our Center for
01:55gastrointestinal cancers are
01:56interdisciplinary approach to research,
01:58education and clinical care and
02:00pancreatic cancer was recently featured in.
02:02Breakthrough is the annual report
02:03of the Yale Cancer Center,
02:05it's Milo Cancer Hospital.
02:06I encourage you to read more
02:08about our efforts there,
02:09or ask about them in the
02:11question and answer session.
02:12Without further ado,
02:13I'm pleased to introduce
02:14our speakers for tonight.
02:16First up will be Dr Jill Lacy,
02:18professor of medicine,
02:19in the section of medical oncology,
02:21will talk be talking about advances in
02:23medical treatment of pancreatic cancers.
02:25She will be followed by Doctor
02:26Ron Salem Landman,
02:27professor of Surgery and
02:29Chief of Surgical Oncology,
02:30who will discuss surgical
02:32management of pancreatic cancer.
02:34Next, Doctor James Carroll,
02:35Professor of medicine in the
02:37section of digestive diseases,
02:39will review risk factors and
02:40screening for pancreatic cancer.
02:42And finally,
02:42Doctor Laura bomb one of our newest
02:45faculty and Assistant Professor
02:46of Medicine in the section of
02:48Medical Oncology will talk about
02:50palliative care in pancreatic cancer
02:52at the conclusion of the talks,
02:53we will answer the questions
02:55that you post in the
02:56Q&A box, and I will moderate
02:57that session and with that I'll
02:59pass the baton to Doctor Lacy
03:00to get started with the talks.
03:13OK, thank you Mandar. Well,
03:15it's certainly a pleasure to be
03:17here this evening.
03:18I'd like to welcome all of you and
03:20thank you very much for taking some
03:22time out of your evening to join us.
03:24So I'm going to provide kind of a bird's
03:28eye overview of pancreatic cancer and then
03:31focus in on our treatment algorithms,
03:33and in particular the systemic therapies.
03:36That we utilized to treat this disease,
03:38and then I'll conclude with some of the
03:41challenges that we face which Mandar
03:43has alluded to and how we are attacking
03:48those challenges moving forward.
03:50So I'm going to start with some basics.
03:54First of all terminology.
03:56What is pancreatic cancer?
03:58When you hear that someone
04:00has pancreatic cancer,
04:01that usually refers to the most
04:03common type of of of tumors
04:05that arises in in the pancreas.
04:07And the more precise term
04:08for pancreatic cancer,
04:09in that context is pancreatic
04:12ductal adenocarcinoma,
04:13commonly abbreviated P deck.
04:15And P tech does in fact represent more
04:18than 90% of all cancers that start
04:21in the pancreas and we now know that
04:24these tumors arise from the cells
04:26that line the ducts of the pancreas,
04:29and so to Orient you.
04:31I have a cartoon here.
04:35Of the pancreas.
04:36So it's large organ or centered in
04:38the mid abdomen and one of its the
04:41main functions of the pancreas is
04:43to produce digestive enzymes that
04:45are carried through this network
04:47of ducts into the first part of the
04:51small intestine or the duodenum.
04:53And pancreatic ductal adenocarcinomas
04:55arise in the cells that line the stocks.
04:59And we now know that there are
05:02changes in these cells.
05:03Precancerous premium plastic changes
05:05that can be identified under the
05:08microscope along with a sequence of
05:11genetic changes that occur before we
05:13have an overt cancer or carcinoma.
05:16That process takes place probably
05:18over about a decade,
05:20but we don't have any mechanism
05:22to either prevent that process.
05:24To really treat it.
05:27Now there are other tumors that
05:29arise in the pancreas and the most
05:31common of those are tumors that
05:33arise in these little islands or
05:35islets of the pancreas.
05:37These are cells that produce hormones
05:39that are involved in metabolism,
05:40most notably insulin, but also others,
05:42Glucagon and neuroendocrine tumors.
05:44As these are referred to are the most,
05:48the second most common tumors that arise
05:50in the pancreas about 5% now P DAX,
05:53and are under tumors are really
05:55completely different diseases.
05:57In terms of their biology treatment,
05:59Natural History,
05:59they share in common origin in the pancreas,
06:03but but really very little else.
06:05Tonight we're going to be focusing in
06:08on PDX pancreatic ductal adenocarcinomas.
06:12Mandar alluded to in his introduction
06:15the challenges that surround pancreatic
06:17cancer and those certainly are
06:19highlighted by the vital statistics.
06:22So as Mandor mentioned,
06:23this is not a common cancer.
06:25Only about 60,000 cases you know
06:27and this compares to lung cancer,
06:29prostate cancer,
06:30breast cancer all over 200,000
06:32cases a year and although it's
06:34about the 10th most common cause
06:36of cancer in the United States,
06:38I believe it is now a
06:40inched into third place.
06:42In terms of leading cause or cause of
06:44cancer related deaths and moving up in
06:46is projected to be in second place next year.
06:48And also in comparison to the common cancers,
06:52lung, breast, prostate, colorectal,
06:54it does have the most discouraging
06:585 year survival at just under 11%.
07:01And for those patients that have
07:03metastatic or stage four disease,
07:05the five year survival is less than 1%.
07:09In addition, the majority of patients
07:1280% present with advanced disease
07:15that cannot be removed surgically.
07:17So only 20% of patients.
07:19Have resectable disease at the outset
07:22and thus are potentially curable.
07:25However, the news is not all discouraging.
07:27There clearly has been incremental progress
07:30for our patients with pancreas cancer.
07:32Patients are living longer with the disease
07:35and more patients are cured of the disease.
07:37Now this is not due to a giant leap forward,
07:40as we've seen in some other cancers,
07:42like Melanoma with immunotherapy.
07:44But again,
07:45to incremental progress with
07:47improvements in surgical techniques
07:48and post out mortality,
07:50which we'll hear about significant
07:52advances in supportive care.
07:55Earlier diagnosis in part because
07:56of the ease of getting imaging and
07:59some improvements in chemotherapy
08:01and other systemic therapies.
08:05So how do most
08:07patients present with pancreatic cancer?
08:10Most patients present with vague and
08:13nonspecific symptoms that can be confused
08:16with many other benign conditions.
08:18Belly pain back pain, some weight loss,
08:22decrease in appetite,
08:23dyspeptic symptoms, nausea,
08:25changing their stool habits,
08:27just generalized fatigue that 50% of
08:31patients do present with sort of an
08:33alarm symptom of yellowing of the skin.
08:35Eyes and darkening of the urine,
08:37or what we call jaundice,
08:39and this is due to tumors located in
08:42the head of the pancreas blocking or
08:45obstructing the bile duct which drains
08:48bile from the liver into the duodenum.
08:51About 50% of patients and may be
08:54more present with either new onset
08:56diabetes within the past year or a
08:58worsening of their diabetic control.
09:01So there is this very interesting
09:04bidirectional relationship between
09:05diabetes and pancreas cancer,
09:06which we are beginning to understand.
09:09Longstanding diabetes does increase modestly,
09:13only modestly.
09:14The risk of developing pancreatic
09:16cancer and pancreatic cancer itself
09:19causes diabetes and then a smaller.
09:22Percentage of patients will
09:23have pancreatitis,
09:24inflammation of the pancreas due to blockage
09:26of the pancreatic ducts by the tumor,
09:29and they may have recurrent bouts of
09:31pancreatitis for unexplained reasons.
09:33So early detection is a challenge because
09:36the symptoms are not alarmed symptoms.
09:38In most patients.
09:39They're vague and nonspecific,
09:40so there's often a delay,
09:42but ultimately the symptoms will prompt.
09:44Usually imaging either an ultrasound
09:46and then ultimately a CAT scan,
09:48which will in most cases show
09:50a mass in the pancreas,
09:52and in most cases will give us great
09:55information about the stage or the
09:57extent of the disease at diagnosis.
09:59But, as I alluded to before,
10:01the diagnosis is often made, so to speak.
10:04Late with 80% of patients inoperable
10:08at diagnosis.
10:10So once we are suspicious of the
10:13diagnosis of pancreatic cancer,
10:14there's a few things that we
10:15need to do in the evaluation.
10:17First and foremost,
10:17we do want to get a biopsy to confirm
10:20the diagnosis and be certain of what
10:21we are dealing with and currently.
10:23We usually will do that via the
10:27endoscope and this is done by our
10:30gastrointestinal GI colleagues and they
10:33will obtain a biopsy via ultrasound
10:36guided biopsy patients who do have
10:39jaundice at diagnosis will usually.
10:40Undergo a procedure called an ER CP
10:43to have a stent placed to open up
10:45the bile duct that will often relieve
10:48symptoms quite rapidly and will allow
10:50for treatment with chemotherapy
10:52for those patients who on their CT
10:54scan had no evidence of spread of
10:57disease to other sites in the body.
10:59We will always want to get a
11:01specialized CAT scan,
11:02we call it a CT pancreatic protocol
11:04scan and this will allow us to
11:07see the relationship of the tumor
11:09to the major blood vessels.
11:11That course through that area,
11:12and to see whether there's any
11:15involvement which in some cases
11:17may delay or even preclude surgery,
11:19and in some cases we will also get a
11:21pet scan that can help with staging
11:23and for all patients.
11:25Now we are having a discussion
11:28about genetic testing.
11:29We're going to hear more about risk factors,
11:31but about 5 to 8% of patients with
11:35pancreatic cancer carry a gene that
11:37they inherited from their mother or
11:39father that has predisposed them.
11:41Or has caused their pancreatic cancer,
11:43most notably the bracket one and bracket.
11:47Two genes that are well associated
11:49with breast and ovarian cancer.
11:51These two genes are also cancer,
11:54causing for pancreatic cancer.
11:56And since 2018,
11:57our professional societies now
12:00recommend that all patients with
12:03this diagnosis consider undergoing
12:05genetic testing to look for a mutation
12:08in their germline DNA that is.
12:11Potentially cancer causing
12:13now why is this important?
12:15Well certainly it can have real
12:17critical implications for the
12:19patient and their management.
12:21For patients that do carry
12:23Braca braka mutated tumor,
12:25we do have a targeted therapy
12:27for these patients.
12:29It is a drug called Elappara,
12:31but has been widely used in bracken
12:35mutated breast and ovarian cancer
12:37and it is a drug that can maintain
12:40a remission from chemotherapy.
12:42And allow patients to be off
12:45of chemotherapy and the cycle
12:47of endless chemotherapy,
12:49and then for those few patients.
12:51And this is less than 1% where we
12:54detect a mutation in a family of
12:57genes that repair damaged DNA so
12:59called MMR or mismatch repair genes.
13:02These are the few patients that will
13:04benefit from immunotherapy genetic
13:06genetic testing obviously has important
13:08implications for family members.
13:10They can be tested and potentially
13:11go into screening and we will.
13:13Hear much more about that later this evening.
13:17So we've done our work up and
13:18we've established this diagnosis.
13:20What next?
13:21It's critically important that
13:23all patients have access to a
13:26multidisciplinary review with
13:28specialists from all the disciplines
13:30involved in caring for this disease.
13:32One major goal of this review
13:34is to review the CAT scan and
13:37to assess receptive abilities.
13:39The patient, a candidate for surgery.
13:42What will preclude surgery is
13:43distant spread of the disease or
13:46extensive vascular involvement.
13:47In this review will also define
13:49the initial treatment at SMILE.
13:51We have a weekly tumor board.
13:53Multidisciplinary review for our patients,
13:56and this is critically important
13:58in establishing their care plan
14:00and optimizing their care.
14:01However,
14:02multidisciplinary care does not end with
14:05the first Tour board review an ongoing,
14:08multidisciplinary management
14:08is really critical.
14:10Again, for optimizing care for our patients,
14:13we may engage our radiation
14:15oncology colleagues.
14:16If patients could benefit from radiation.
14:18Are Gastro Enterology colleagues are
14:20always involved in the care of our
14:23patients managing duodenal obstruction?
14:25Biliary obstruction re biopsying
14:28and then our period of care team
14:30is really critical in helping
14:32manage the tumor related symptoms.
14:34So I'm going to pivot now to our
14:37treatment approach to this disease.
14:39And as is true,
14:40in most cancers that is going
14:42to be driven by the extent of
14:44disease or the so-called stage.
14:46In a pancreas,
14:47cancer really categorized
14:48patients into three stages.
14:50Those who have resectable disease,
14:52no metastases, and no blood vessel
14:54involvement at the other end of the spectrum,
14:56those who already have disseminated
14:58disease to other sites,
14:59metastatic or stage four disease
15:02with the liver belly cavity lung.
15:04And lymph nodes being common sites.
15:07And then there's this middle group where
15:09there is no evidence of distant spread,
15:11but the tumor is growing up to
15:14touching and growing around blood
15:16vessels that are in that area.
15:18This group is a continuum from very
15:21little blood vessel involvement
15:22to quite extensive and has been
15:24broken down into two groups.
15:26Those where there's very little
15:28blood vessel involvement.
15:28We define those as borderline resectable,
15:31so potentially candidates for
15:33surgery and those who have.
15:34Extensive involvement with tumor
15:36growing around major blood vessels and
15:39those are defined as locally advanced,
15:41unresectable.
15:44And then we need to really have a
15:46meeting and a discussion with our
15:49patients about the our goals of our
15:51treatment and those that are resectable
15:54or who have borderline resectable disease.
15:57Those are those patients clearly
15:59are potentially curable,
16:01and it's about 30% of our patients.
16:03Those that have metastatic
16:05disease treatment is palliative,
16:06but in 2021 we still do not
16:08have a cure for those patients.
16:11And then for this group that
16:12have no metastases but locally.
16:14Janssen resectable disease.
16:15This is a treatable subset.
16:18These patients can actually live years.
16:21In some cases.
16:22A few of them will get to surgery if
16:25the tumor shrinks off the blood vessels.
16:28But there is a low rate of cure
16:30for this subset of patients.
16:31And then in terms of the treatment algorithm,
16:33it's highlighted here.
16:36For patients who are resectable surgery,
16:39is is really the centerpiece
16:41of always has been.
16:42But surgery alone cures a
16:45small percentage of patients,
16:47and so using chemotherapy and in 2021,
16:50that is the complicated three
16:52drug regimen Folfiri Knox,
16:54we have really dramatically increased
16:56the cure rate for these patients.
16:59So six months of chemotherapy is generally
17:02the recommended treatment course,
17:03along with surgery for these patients.
17:05For those that do a blood vessel involvement,
17:07we really now have moved towards
17:10administering chemotherapy initially
17:11to virtually all of these patients
17:15to reduce their disease burden
17:18and hopefully enhance the success
17:21rate of surgery and and then,
17:24after usually four to six months,
17:26they may become surgical candidates
17:27if surgery is not possible,
17:29they often will go on to radiation
17:31to maintain protracted Disease
17:33Control and then for our patients
17:35with stage four metastatic disease.
17:37We will be generally treating
17:39them with Kelly of chemotherapy,
17:42so I mentioned the progress in
17:43this disease has been incremental,
17:45and that's largely true,
17:46although in our patients with
17:48Resectable disease,
17:49I think we can say that we did
17:51have a giant leap forward in 2018.
17:54So prior to that period of time,
17:57about 20% of patients present with
18:00respect resectable disease and with
18:02surgery and the chemotherapies
18:03that we were using up to that
18:05point only about 20 to 25%.
18:07Of those patients were cured
18:09in 2018, we learned about the results
18:12of a pivotal trial using full fear
18:15knocks after surgery for six months.
18:17In these patients who've undergone surgery,
18:20and that a treatment doubled the survival.
18:23The five year survival from
18:25about 25% to nearly 50%,
18:26and that was heralded as an immediately
18:29practice changing observation and really,
18:33truly was the biggest advance for pancreatic
18:35cancer that we had seen in my career.
18:37And in the previous 25 years,
18:40so just a few comments about the
18:42regimens that we use in pancreas cancer.
18:44The standard of care FDA approved
18:47list is quite short.
18:49Highlighted folfirinox this is a regimen
18:52that has made a difference unprecedented
18:54benefit in all stages of disease.
18:57It is an essential component
18:58of curative treatment,
18:59but the benefit of Folfiri Knox is it's
19:02some expense in terms of quality of life.
19:05It can be associated with significant
19:07toxicities and side effects so it can
19:10be a tough regimen for for for some
19:12of our patients a couple years after
19:14we learned about full fear in oxen,
19:16it was first evaluated in stage four disease.
19:20Then we learned about a two drug
19:22regimen which is now widely used
19:24in the metastatic setting.
19:25Jim cited in Annette Paclitaxel a simpler
19:28regimen than full fernox better tolerated,
19:31particularly in our older
19:33and frailer patients,
19:34and it is on a regimen that we can
19:37also use in our locally advanced,
19:39unresectable patients.
19:42Or in AT Canon old drug,
19:44it's in the FOLFIRINOX regimen
19:46has been reformulated,
19:47and this may have some advantages,
19:49and this is also used in
19:51the metastatic setting.
19:52We have at present only two targeted
19:55drugs that we can use in this disease.
19:57I've already mentioned elaborate for those
20:00patients with abraka mutated pancreas cancer.
20:03It improves Disease Control as a
20:06maintenance treatment after induction
20:08folfirinox and does allow patients
20:11a break from endless chemotherapy
20:13and then immunotherapy,
20:15which has been so critical for increasing
20:18the cure rate of other cancers,
20:20can be used in that 1% of
20:22patients that carry.
20:24Uhm,
20:24this miss Metro Fair repair
20:27deficiency in their tumors DNA.
20:30Now,
20:30in contrast to resectable disease
20:32that we really haven't had a
20:34major leap forward in terms of
20:36progress in the metastatic setting,
20:38although in 2011 full fernox did
20:40did emerge as a major advance with
20:43a doubling of the median survival
20:45in patients with metastatic disease
20:47and is now widely used along with
20:50the other regimens that I mentioned.
20:52So there has been an acceleration in
20:54the pace of of drug discovery and
20:57improvements in treatment in metastatic.
20:59Setting so this is a busy complicated slide.
21:02I do apologize but but it is the
21:05algorithm that we incorporate
21:07in treatment decisions for our
21:09patients with metastatic disease.
21:11Now the vast majority will
21:13be this middle group,
21:15but I do want to highlight that
21:17when we are dealing with metastatic
21:19disease in addition to the genetic
21:21testing for mutations that a
21:23patient may have inherited,
21:24we also strongly recommend
21:26and attempt to do this in
21:28every patient and that is.
21:30What's referred to as tumor profiling or
21:33genetic profiling or molecular profiling.
21:36So this is analysis of the
21:37DNA of the tumor itself.
21:39We will always find mutations and
21:42what we're really looking for
21:44are mutations for which we may
21:46have a drug that may be active so
21:48actionable or DRUGGABLE mutations.
21:50Again, most patients will
21:52fall into this middle group.
21:54No bracket mutation,
21:55I know deficiency and mismatch repair.
21:59They will usually be treated with chemo.
22:01Therapy for those that are broken,
22:03mutated chemotherapy and then maintenance.
22:05Elaborate is an option,
22:06and those few patients who have
22:09MMR deficiency can go on and
22:11receive immunotherapy.
22:12I've highlighted at the bottom enrollment
22:14in a clinical trial in this disease is
22:17always a consideration at every phase,
22:19from beginning to the last line of treatment.
22:24So Mandar a highlighted at the beginning
22:27the challenges of pancreatic cancer.
22:29And I,
22:30I'm I'm highlighting the same here.
22:33I've already alluded to the fact that most
22:36patients present with advanced disease,
22:38so the challenge is that we
22:39do not have an easy,
22:40accurate screen for the general population
22:42for early detection of this disease.
22:45And then there are really complex biological
22:49challenges that have really challenged
22:52us in developing new therapeutics,
22:55and I again highlighted just
22:56a few of them here.
22:58This is a tumor that infiltrates
23:00locally around blood vessels,
23:01so it makes resection more difficult.
23:04It metastasizes early and often,
23:07often before we even see a mass on imaging.
23:10UM,
23:10this tumor grows in a protective
23:13complex star like material or stroma,
23:17and that really,
23:18we talk about a protective
23:21shield that this confers,
23:23interferes with immune effector
23:24cells and chemotherapy.
23:26Penetrating the tumor while at the same
23:28time giving the tumor growth advantage
23:30pancreatic ductil adenocarcinomas are,
23:34unfortunately.
23:35Invisible to the immune system,
23:36in part because of this stroma,
23:38and thus they are resistant to the
23:41current immuno therapies that have
23:42been so impactful in other tumors
23:44and then in pancreatic cancer.
23:46We do encounter recurring
23:49very common mutations,
23:50notably a gene called K Ras is mutated in
23:54more than 90% of patients and peer FP53
23:57right behind and for all of my career
24:00until literally the last year or so.
24:02Certainly these have been considered,
24:04not.
24:05Druggable,
24:05but now we have a drug that's FDA
24:08approved for a specific KRS mutation,
24:11and there are a whole host of other
24:12drugs in the pipeline that will be
24:14coming into the clinic in the next
24:16year or two that that should be
24:18targeting some of the mutations in KRS
24:20that we encounter in pancreas cancer.
24:22So our understanding of these
24:24challenges as difficult as it is
24:27to list them really is helping us
24:30to develop new therapies really
24:32to get at these challenges.
24:37So it's not all discouraging.
24:39I think really there is much hope
24:42in terms of what's on the horizon,
24:44so certainly immunotherapy,
24:45I think, will become an effective
24:48tool for treating this disease.
24:51We're not there yet,
24:52but there's intensive research.
24:54I'm looking at new
24:55immunotherapy combinations.
24:56We have a number of trials at Yale looking
24:59at combining New Immunotherapeutics
25:01with the current generation,
25:03along with other strategies
25:05including chemotherapy.
25:06And I think we'll get there.
25:08There's intense interest in
25:09looking at drugs to disrupt,
25:11to disrupt that protective and growth,
25:13promoting stroma or scar like tissue.
25:16This is a new area,
25:17but I think this holds great promise and
25:20these drugs will likely be combined with,
25:23for example,
25:24immunotherapy or chemotherapy
25:26to enhance effectiveness.
25:28I mentioned inhibitors of care
25:29as we know that's coming.
25:31I think that's one of the most incredible,
25:33most the most exciting
25:35possibilities in the future.
25:37For patients with PD and again
25:39we expect these drugs to be in
25:41the clinic in the next few years.
25:43Another strategy that's really
25:45just getting going is targeting the
25:48very altered metabolism and energy
25:51utilization of pancreatic cancer.
25:53We can utilize that and exploit
25:55that to treat cancer.
25:57This cancer and then finally more
26:00drugs that we can use to exploit
26:04the impaired repair of damaged DNA.
26:07It occurs not only in the
26:08Baraka mutated tumors,
26:09but in many other of our
26:12pancreatic cancer patients,
26:13and we're learning this as we do more
26:15genomic analysis on these tumors.
26:17I think ultimately we'll be
26:19seeing combination strategies.
26:20I mentioned targeting the stroma
26:23in combination with immunotherapy.
26:25Also with chemotherapy,
26:26and I think that is going
26:28to be the key to the future,
26:30so I think we're really expecting to
26:33see an explosion of new therapies
26:35coming online over the next decade.
26:37It's certainly I know to this
26:40audience cannot come quickly enough,
26:42but I think there certainly is
26:44every reason to be hopeful.
26:47And thank you.
26:52Thank you, Doctor Lacey will
26:53move on to Doctor Salem.
27:05Share my screen.
27:14Can you see my screen?
27:18Well, thank you too.
27:20Man offer the introduction and thank you
27:23to everyone for joining us this evening.
27:25It's particularly nice to see
27:27some the names of some individuals
27:29who I've known for so long,
27:32as well as some individuals who I've had the
27:35pleasure only of meeting rather recently.
27:37So thank you so much for joining.
27:40How like to present to you some of the
27:43some of what we do in the surgery for
27:46pancreas cancer and some of the challenges.
27:49Where I think we have had advances,
27:53so this is from the.
27:56The cancer database and here you
27:58can see that in the estimated number
28:00of new cases of pancreas cancer
28:03in 2021 is about 60,000,
28:04and this has actually gone up fairly
28:07substantially over the course of time.
28:10The estimated death rate is 48,000.
28:14As you can see here,
28:15which is round about the time that I
28:18started doing pancreas surgery at Yale.
28:20The death rate,
28:21and the new cases rate was almost identical.
28:25And as you see,
28:26as time it's done on these two
28:29lines have parted slightly,
28:30but we so do wish that they would
28:33actually diverge a little bit more,
28:34and as you heard the relative
28:37survival rate is 10.8%.
28:39But we do have hopes that the
28:42survival rate will go up with some
28:44of the modalities that doctor
28:46Lacey explained to you,
28:47and some of the other areas that
28:49you will hear about shortly.
28:51And as you just heard in the
28:54previous presentation, only 20%.
28:56Of patients who identified initially
28:58with pancreas cancer are able to
29:01undergo surgery and in patients
29:03who do not undergo surgery,
29:06there is no five year survival.
29:10So the surgical management of pancreas
29:12cancer starts with the worker and
29:15I tell patients that there are two
29:17things that you have to do first.
29:19First of all,
29:20you have to ensure that there is
29:23no evidence of spread and secondly
29:25you have to ensure that the tumor
29:27is removable and as you heard,
29:30by and large,
29:31that in that revolves around the
29:33fact that the tumor does not involve
29:36any major any of the major blood
29:38vessels in such a way.
29:40That they are not re constructable,
29:42and in addition we have to determine
29:45that the patient is sufficiently
29:46healthy in order to tolerate the
29:49surgery which on occasion can be very,
29:51very extensive.
29:52And it's also important for us
29:54to stage and classify the disease
29:57according to what you heard with
29:59my doctor Lacey into Resectable
30:02borderline locally advanced and
30:03metastatic and the treatment of these
30:06is as already discussed by Doctor Lacey.
30:09So let me show you the pancreas.
30:11The pancreas is that banana in the middle.
30:14That sort of brownish area
30:16that is surrounded.
30:17Here's that brownish here.
30:19This is the pancreas.
30:20It's surrounded by the smaller
30:22beginning of the small intestine.
30:24Or duodenum it has the bile duct
30:26going through it right through it,
30:28as the gallbladder close by it has
30:31the artery to the small intestine,
30:33which is known as the
30:35superior mesenteric artery.
30:36And the vein that takes the blood back,
30:38which is a superior mesenteric vein.
30:40And finally, the portal vein.
30:43And as many and as many of you know,
30:46the pancreas is divided by two
30:50imaginary lines into the head.
30:53The body and the tail.
30:57And the surgery or the type of section that
31:00is carried out depends on the location.
31:03If the lesion is in the head,
31:05we carry out a whipple procedure
31:07that you may have heard of,
31:09and sometimes a pilaris
31:10preserving Whipple procedure,
31:12which we shall explain shortly.
31:14If the lesion is in the body or the tail.
31:17We do what's called a distal
31:20pancreatectomy and splenectomy,
31:22and I'll explain the reason
31:24for the splenectomy shortly.
31:26So as many of you have
31:28actually seen in the past,
31:29and for all of my patients
31:30who come to see me,
31:31this is a diagram that I will always draw
31:35to explain the actual process of resection.
31:38So I would like to do that now.
31:40So here's the esophagus.
31:42Yes, that takes food all the way
31:45down into the stomach.
31:46And here's the stomach.
31:47This is the beginning of the
31:49small intestine or the duodenum.
31:50And here's the pancreas and the
31:52pancreatic duct that goes right
31:54through the pancreas itself.
31:56Here's the liver.
31:57This is the bile duct,
31:59and he has the gall bladder.
32:01So that's the anatomy of the area.
32:05Now when we talk about a tumor,
32:09a pancreatic adenocarcinoma
32:10in the head of the pancreas,
32:13this is the type of surgery that's required.
32:17This is what needs to be removed.
32:20We have to remove the head of the
32:24pancreas along this red line here.
32:26We have to remove the bottom parts of
32:29the bile duct along with the gallbladder.
32:33We have to remove a portion of
32:35the small intestine as shown,
32:38and occasionally we'll need to
32:40remove some of the stomach as well.
32:42Depending on how advanced and
32:45large the tumor is,
32:46this is the pie loris which separates
32:50the stomach from the duodenum.
32:52And if we have to take a portion
32:54of the stomach,
32:55this will be known as a classic whipple
32:59procedure or a pancreaticoduodenectomy.
33:02If we are able to save the pie loris,
33:05then we will carry out a pie loris,
33:07preserving Whipple procedure or a pilaris
33:10preserving pancreatico dude and ectomy.
33:13And once that resection is done,
33:17the pancreas gets joined or anastomosed
33:20to the small intestine like this.
33:23The bile docs, now,
33:24without the gold that it gets,
33:26joined to the small intestine like
33:29this and the and the beginning
33:31of the duodenum or stomach,
33:33gets joined to the intestine like this,
33:36and so that's the reconstruction
33:39that we would see.
33:41Post whipple procedure.
33:44At how do people do after
33:45the Whipple procedure?
33:46Well,
33:47it's approximately a six hour operation.
33:50It's not common that people would
33:52require a blood transfusion
33:54about 5 to 10% of the time,
33:56and in general patients will stay one
33:58night in the surgical intensive care unit.
34:01On postoperative days one and two
34:04we will start fluids by mouth and
34:07on the 3rd and 4th day patients
34:09will start taking solid food and
34:12if there are no complications the
34:14average day of discharge will
34:16be approximately on day five,
34:18sometimes as little as early,
34:21rather as day three.
34:23But sometimes you can get complications
34:25which will come to after surgery.
34:27Patients find that they're only able
34:30to eat small meals.
34:32And so they'll have to have meals
34:34about half the size of normal and have
34:36a good size snack in between meals.
34:39And this is something that will need to
34:41take place for approximately 6 weeks,
34:43but by about 6 to 8 weeks,
34:45the vast majority of patients
34:48are back to eating normally.
34:51Now the majority of the cells
34:53that create insulin are in the
34:55body in the tail of the pancreas.
34:58So after the Whipple procedure,
35:00it's unlikely that patients
35:02will require insulin.
35:03If they were not diabetic prior to surgery.
35:06Now the pancreas, as Doctor Lacy,
35:09pointed out also creates enzymes
35:11to help us with digestion,
35:13particularly fats,
35:14and those enzymes are evenly
35:16distributed along the pancreas
35:18and often patients with pancreas.
35:21Cancer will already have some
35:24degree of enzyme deficiency,
35:27and oftentimes patients who have
35:29a whipple procedure for pancreas
35:32cancer will require pancreatic
35:35enzyme supplementations,
35:36and this will take place by taking a
35:39pill right at the very beginning of the meal,
35:42or just at the time of taking a large snack.
35:46Now,
35:46as I mentioned,
35:48there are complications that are
35:50associated with an operation of this
35:52magnitude and the the complications we
35:55see the most would be and anastigmat eclec,
35:58which means leakage from one
36:00of the reconstructions,
36:02and that most commonly is
36:04reconstruction of the pancreatic duct.
36:07Interestingly,
36:07and those patients who receive a
36:10whipple procedure for pancreas cancer,
36:13the likelihood of a pancreatic
36:15duct leak is much lower than
36:18patients who receive a whipple
36:20procedure for other reasons.
36:22Patients may find that it just takes time
36:24for the stomach to start working again,
36:27and we call that delayed gastric emptying.
36:30It's a nuisance,
36:31but it takes time and eventually it resolves.
36:34You can get bleeding,
36:36you can get infection,
36:37and you can even die from this operation.
36:41Now in the centers around the country
36:43that are high referral centers.
36:46In other words, places where they
36:47do a lot of Whipple procedures,
36:49the mortality rate of this operation is.
36:52About 3% that means three out of every
36:55hundred patients will die from the procedure.
36:58If you look at places where the the
37:02the volume is much lower the incidence,
37:05the mortality can be up to 20%,
37:08which is really very high in our institute.
37:11Here at Yale,
37:13the mortality rate is 1%.
37:16Of course we can also get the complications
37:18you get with any type of surgery.
37:20You can get blood clots.
37:21You can get pneumonias.
37:22You can get other infections such as urine,
37:24infections and other infections
37:26can take place as well.
37:28Now all of these complications are
37:31reduced in high volume sentence and
37:33that's really very very important
37:36and we've identified that fact
37:38over the last 10 to 15 years and
37:41increasingly now patients with
37:43pancreas cancer requiring surgery.
37:46Will be referred to high volume centers now.
37:49Dr.
37:50Lacy pointed out that this is a
37:53multidisciplinary type of care
37:55that's required.
37:56But in addition to that,
37:58the type of care that's required
38:00is the care that you see
38:02in high volume centers.
38:03Nurses who are able to identify
38:06problems before they become dangerous.
38:10Surgical intensive care units that
38:12can treat patients with complications.
38:15Interventional radiology.
38:16And interventional gastro enterology.
38:19Who can help us with complications
38:21and avoid any long term morbidity and
38:24clearly any long term mortality that
38:27might be associated with this procedure.
38:30I shall move on now to distal
38:33pancreatectomy and splenectomy,
38:34which is the procedure that is
38:37used for tumors that are located
38:40in the pancreatic body and tail.
38:43Now we take out this part of the
38:45pancreas because that's where the.
38:47It is located but many patients ask well,
38:50why do you take out the spleen
38:52and the answer goes like this,
38:53that the blood vessels that go
38:56to the spleen are very closely
38:58approximated to the pancreas,
39:00and if one tries to preserve them
39:03one risks leaving some cancer
39:06on those blood vessels,
39:08and in addition the lymphatic drainage,
39:12the drainage where cancer goes to
39:14lymph glands goes towards the spleen,
39:16so many of them.
39:18Times when there is metastatic
39:20disease to lymph nodes,
39:21those lymph nodes are located
39:23around the spleen and hence the
39:26spleen needs to be removed.
39:27This procedure is shorter
39:29than a whipple procedure.
39:30It's only about 3 hours.
39:32No reconstructions are necessary and
39:34no removal of any intestine is required.
39:38This pay this operation is
39:40often done laparoscopically.
39:41Lee,
39:41the hospital stay is only three
39:43days on average and there's no
39:46need for intensive care units.
39:47And there is a quicker recovery now.
39:51The function of the pancreas will
39:53generally be preserved by what's
39:55being left behind in the head
39:57and the neck of the pancreas.
39:59But the the loss of the spleen.
40:01Most of the functions of the spleen
40:03will be taken over by the liver,
40:05all except for one which is the
40:07ability to protect oneself against
40:09three different infections.
40:112 pneumonias and a meningitis.
40:14And when you take out the spleen we
40:16will give immunizations against.
40:18Those three infections sub patients
40:22are covered.
40:24So as we as we outlined right
40:27at the very beginning,
40:29what are the advances and the
40:31advances in the surgical management
40:33of pancreas cancer revolve?
40:35Mainly around several issues.
40:37Several several domains.
40:39When is that identification
40:40of early stage disease,
40:42which I think you may hear
40:44from Doctor Farrell.
40:45Now we know that there are
40:49certain disease processes that.
40:51That predispose one to pancreas
40:53cancer and they are pre malignant
40:56in nature and we also know that
41:00improvements in these survival
41:02rates and pancreas cats are really
41:04quite difficult to combine.
41:06So if we can identify a patient who
41:09has a lesion that is just about to
41:12become malignant or has become only
41:14just malignant at the earliest stage,
41:17we are offering the patient
41:20a great advantage by.
41:21Curing them or avoiding a disease
41:24that has a very high mortality rate.
41:27We certainly know that we are able
41:30to make certain unresectable tumors
41:33receptable by neoadjuvant therapy.
41:36Whether that translates into improved
41:39long term survival is unclear,
41:41and the treatment of patients in
41:43high volume centers is some things
41:45that I have alluded to already.
41:47But what have we done here?
41:49So at Yale, what we've done over the last
41:5215 years is we've done a very thorough
41:55analysis of all the modifiable risk.
41:57Factors that exists for complications.
42:01We've identified what we can do to
42:04reduce the pancreatic fistula rate.
42:06We've identified what we can do
42:08to reduce delayed gastric emptying
42:10and to reduce the length of stay
42:13in hospital and facilitate early
42:16treatment with chemotherapy.
42:17So many of these patients have systemic
42:20disease that are cults that if we can get
42:24them on to chemotherapy expeditiously,
42:26we're offering them best opportunity.
42:28Of cure In addition to that,
42:31we enroll our patients in international
42:33quality outcome databases where
42:35we're able to compare our results
42:38with adults and we're able to learn
42:40how to improve our management by
42:42the evaluation of large databases.
42:45Lapre Scopic and robotic approaches
42:48are present,
42:49but currently they don't appear
42:51to be ready for primetime and have
42:54not yet really improved the outcome
42:57of these patients.
42:58So we enrolled our pay all of our patients.
43:01Into the national surgical quality
43:04improvement projects and have found
43:07that our fistula rate and our rate
43:10of delayed gastric emptying is
43:12in the top 10% of the country and
43:15our length of stay is simile.
43:17So so this work has paid off and gives
43:20an idea of how this is an area where so
43:23many different disciplines come together.
43:27In order to provide the very
43:29best outcome to our patients.
43:32And we are extremely grateful to
43:34our nursing staff to our radial
43:36interventional radiologists and
43:38gastroenterologists for what they do
43:40to help us in the man in the surgical
43:43management of this disease process.
43:46And one of my patients who had a
43:49whipple procedure in many years ago
43:51decided to name their pet goat Whipple.
43:53And here is a picture of them.
43:56So hopefully if you have any questions,
43:58hopefully I've answered some of
44:00the questions that you might have
44:02and we look forward to questions
44:03at the end of this session.
44:05Thank you very much.
44:08Thank you Doctor Salem. Please
44:10enter your questions into the Q&A
44:12box at anytime and we'll get to
44:14them at the conclusion of the talks.
44:28I'll take it from here.
44:30Thanks again. Mandarin to smilow
44:33for organizing this evening.
44:36I know it's late and I appreciate
44:38everybody being here and
44:40participating in this symposium.
44:42You've heard a talk about treatment from
44:45both surgical and medical perspective.
44:48My goal in life is to be at
44:49the other end in terms of early
44:51detection and finding this sooner.
44:53Understanding how this disease occurs
44:54and who's at risk for getting it.
44:57So I've been tasked with dealing
44:58with and talking about risk factors
45:00and screening for pancreatic cancer.
45:04There we go.
45:07So some of this has been covered already,
45:09but I think it's worth making
45:11the point that unfortunately with
45:13pancreatic cancer specifically.
45:15A lot of the symptoms that we deal with.
45:16They're very nonspecific,
45:17and as you've heard, are often late,
45:20and so there's not one symptom.
45:23That points to saying, oh,
45:24this is clearly a problem with the pancreas.
45:27A lot of the symptoms that we deal with
45:29could be attributed to your stomach
45:30or your gallbladder or your colon,
45:32for example,
45:33and this needs to be kept in mind
45:35and also in terms of perspective for
45:38individuals concerned about having
45:39this disease and realizing that you
45:41know it's still an uncommon disease.
45:43Although certainly rising incidents
45:45and there are many,
45:46many other benign conditions of
45:48the GI tract and abdomen that can
45:51also present with similar symptoms.
45:54This has also been mentioned before in
45:56terms of how this disease is changing
45:59overtime and becoming a more common disease,
46:02and with these concerns that by
46:042030 or so that it will probably
46:06be account for a large number of
46:08cancer related deaths of all the
46:10entire Council population.
46:12And while there have been advances
46:15with respect to the treatment and
46:17you've heard about some great advances
46:19with respect to medical treatment
46:21and surgery with pancreatic cancer.
46:23We do believe that there needs
46:25to be further advances made with
46:26respect to early detection,
46:28similar to what you've heard when
46:29people talk about colon cancer
46:31screening or breast cancer screening.
46:33So I'm going to broadly talk about,
46:35you know some ideas relating to
46:36this for the general population
46:38as well as the high risk groups.
46:40Specifically when we talk about
46:42the general population,
46:43the idea will be very similar to
46:45having a colonoscopy at the age
46:47of 50 or breast cancer screening.
46:49That's something we could apply to everybody,
46:51not just people, at increased risk.
46:53And so there is increased interest in
46:55this area with respect to blood tests
46:57and the possibility of could there
46:59be a blood test that everybody could
47:01get access to that would pick up.
47:03Pancreatic cancer early,
47:05and there's a lot of different tests
47:06that are you going to hear more and
47:08more about it over the next couple of years.
47:10This is one particular type of blood test.
47:11It's a what's called a multi
47:13cancer blood test,
47:14so this is a blood test that's
47:16designed to actually identify
47:17multiple different types of cancer,
47:19not just pancreatic cancer.
47:21For this one,
47:22this is called cancer seek and the
47:24study that was designed to analyze
47:25it was called the tech study,
47:27and this was designed to identify
47:29colon cancer, breast cancer,
47:31ovarian cancer, kidney cancer,
47:32but also pancreas.
47:34Cancer and this particular study
47:36had to study about 10,000 patients
47:39and of those 10,000 patients,
47:41only 134 patients had a positive
47:45abnormal blood test and ultimately
47:47only 26 cancers were detected.
47:50So this just gives you a broad idea
47:53about how challenging this area is,
47:55but also how uncommon some of
47:58these diseases that were
47:59actually trying to chase are.
48:01Over on the right hand side here a lot
48:03of the Councils that were found turned
48:04out to be breast cancer or lung cancer,
48:06and interestingly there were no pancreas
48:09cancers identified in this particular study.
48:11Again, this is a multi cancer blood test.
48:13It tries to identify a broad
48:16sweep of different cancers.
48:18So there have been some advances to
48:20try and develop cancer blood tests
48:22that are more specific for pancreatic
48:24disease and pancreatic cancer.
48:26This is one particular type,
48:28called the Imrei panic and deep study,
48:31that uses a variety of blood markers.
48:33They're kind of pooled together and tested.
48:36And when you hear about this test,
48:38you hear some very positive things about
48:40it in terms of how good it functions.
48:42We talk about operating characteristics.
48:44But the reality is,
48:46is that when this when this blood test
48:48is then applied to a general population,
48:51it results in what we call a
48:53lot of false positive tests.
48:54Meaning people are told that
48:56they have a positive blood test.
48:58But after we complete the work up,
49:00which could include CAT scans
49:02and MRI scans and endoscopies,
49:04the vast majority of patients will
49:07not end up having cancer for sure.
49:09We will find some, but it causes.
49:11You can imagine a lot of unnecessary worry.
49:14So this is one of the major problems.
49:16The challenges we have when we try to
49:18develop tests for the general population.
49:21And that's why we then start to focus
49:23more on what we call high risk groups.
49:25So people who are at an increased
49:28risk of developing pancreatic cancer.
49:31One of these groups are individuals
49:32who have pancreatic cysts.
49:33This was alluded to by Doctor
49:35Salem earlier on pancreatic cysts.
49:37These are little fluid collections
49:39in the pancreas are incredibly
49:41common in the population,
49:42maybe about 6 million people in the
49:45United States alone probably have
49:46some form of a pancreatic cyst.
49:48They're picked up,
49:49incidentally by CAT scans or
49:51MRI scans are done.
49:52Here's a small little sis
49:54sitting in the pancreas,
49:55or here's an MRI scan showing multiple cysts.
49:58And we know for a fact that
50:00some of these cysts, again,
50:02not all of these cysts,
50:03but some of these cysts can go on
50:06and develop a cancer in the system.
50:08This is something that we're
50:09concerned about and we follow,
50:10and we do a lot of investment
50:13investigations to figure out.
50:14Interestingly,
50:14we also know that's in patients
50:16that have these cysts.
50:18They may also develop a pancreatic
50:20cancer somewhere else in the gland,
50:22albeit at a very small race.
50:25But it's important to make the
50:27point that the vast majority of
50:28people who have pancreatic cysts,
50:30despite everything that I've said,
50:32uhm, nothing happens.
50:34There.
50:34Cyst doesn't change.
50:36They certainly don't
50:37undergo pancreatic surgery,
50:39and the vast majority do not develop cancer.
50:42So a lot of work and emphasis
50:43is in this area trying to figure
50:45out which patients are truly at
50:46risk in which patients are not.
50:50Another high risk group are those
50:53individuals that have either a familial
50:56or genetic risk of pancreatic cancer.
50:58I won't challenge people to tell me
51:00who these people in the picture are,
51:02but it's important to understand
51:05that if you have increasing numbers
51:07of first degree relatives in your
51:09family with pancreatic cancer,
51:11your risk of developing type
51:13attic cancer actually increases.
51:15So as you go from having one
51:17firstview relative to two first
51:18degree relatives all the way up to.
51:20Three first degree relatives,
51:22your relative risk,
51:23your rate of developing,
51:25or your risk of developing pancreatic
51:27cancer increases significantly when
51:29we look at this and try to understand
51:31what's being inherited here.
51:33What are the genes the most
51:35common gene found in this scenario
51:37is the bracket to gene,
51:39but it still doesn't account for
51:41the vast majority of patients.
51:43Who had this familial risk?
51:45And so we don't understand everything
51:48about familial pancreatic cancer.
51:49Maybe it's a shared environmental issue.
51:51Maybe it's the microbiome.
51:53Maybe it's the bugs in your gut
51:55that are contributing to this.
51:56I will apologize for this slide,
51:58but I've tried to make it as a as
52:00as as more readable as possible,
52:02but it's an important slide.
52:04Here is a list of the currently
52:07accepted based cancer susceptibility
52:08genes that are in all our DNA that we
52:12carry around what we call our germ
52:14line as opposed to being in the tumor.
52:18They're they're listed here
52:18on the left hand side.
52:19You've heard about some of them
52:22before those bracket two ATM.
52:23There's some particularly high risk
52:26ones called like CDKN 2A or P16.
52:29There's a cootie georgene down here STK 11.
52:33There's also an intermediate
52:35risk group including bracket,
52:37two ATM and PAL B2,
52:40and then some lower risk genes such
52:42as those seen in Lynch syndrome.
52:44And these all have a varying rate
52:47of risk or relative risk of of
52:50the developing pancreatic cancer.
52:53But on the flip side,
52:54they're also found in individuals who
52:57present with sporadic pancreatic cancer.
53:00There are also associated as
53:01you can understand for,
53:03like with bracket two in bracket,
53:04one with the risk of developing
53:06other cancers such as breast
53:07cancer and ovarian cancer.
53:09So what do we do with
53:10this type of information?
53:11This information that
53:12we have available to us.
53:14One thing is weird.
53:15Able to risk or give advice to people
53:18about lifestyle modifications.
53:19So for example,
53:21hereditary pancreatitis is a
53:22well characterized gene that's
53:24inherited or patients present with
53:26recurrent attacks of pancreatitis
53:28at a relatively early age.
53:30By the time that their their pancreas
53:33is disease and is resulting in
53:35problems with absorption and diabetes
53:37there well into their 20s and 30s
53:39and then the risk of pancreatic
53:41cancer takes off at a much earlier
53:43the age than the general population.
53:45In these patients,
53:46age of 40s and 50s.
53:49What we know is that if these patients smoke,
53:53and if we ask these patients to smoke,
53:55stop smoking because smoking is
53:57a significant risk factor for
53:59pancreatic cancer, they can reduce
54:02their risk of developing chronic cancer,
54:04we assume, but we actually don't have
54:06a lot of data that this applies to
54:09other genetic risk factor individuals.
54:12Such as the bracket, two population,
54:13but we certainly assume that's likely true.
54:16The second thing that we do with this
54:18sort of information about knowledge
54:19of genes that we we carry that
54:21increase people's susceptibility.
54:23Developing pancreatic cancer is developed.
54:25Some form of surveillance program to try
54:28and see if we can find either the cancers
54:31early or even the pre cancers early.
54:33This is doctor Lacy and Doctor Salem
54:36alluded to really takes a multidisciplinary
54:38approach where a combination of imaging
54:41with radiology such as an MRI and or CT
54:44scan in combination with an endoscopic.
54:45Percent take a very close look at the
54:48pancreas to see if we can identify again.
54:50Early masses or cysts that are concerning
54:53the pancreas that we would recommend.
54:55Patients undergo surgical resection for
54:58to either manage an early cancer or to
55:01manage patient who has a pre invasive lesion.
55:05For this we have a pancreatic cancer
55:07early detection clinic established
55:09through the SMILOW Cancer Genetics group
55:11and through this group we look and we
55:14follow a large group of patients in our
55:17pancreas cancer surveillance program.
55:19These groups I've kind of alluded to before,
55:21but I'll just go over them one more time.
55:23There's a high risk groups such as those
55:26individuals would put Fiaker syndrome.
55:28There's this very large cohort of
55:30individuals who have just a family history,
55:33be it two or more.
55:34First or second degree relatives
55:36with pancreatic cancer,
55:38but no obvious germline gene abnormality
55:40that we can find on a blood test.
55:43Then there are those variety of individuals
55:46who carry germline mutations in their
55:48blood and for most of these individuals,
55:50I think it's important to stay.
55:52They need to have at least one family
55:54member with pancreatic cancer before
55:56their risk becomes significant.
55:58The exceptions are P16 for this
56:01particular group and then finally
56:03the group of hereditary pancreatitis
56:05that I alluded to before.
56:08So far we're falling about 205 patients,
56:11again with a broad inclusion of indications
56:14including predominantly family history alone,
56:18as well as a large cohort of
56:20individuals with BRACA 2 gene mutations.
56:24The third thing that we do with this
56:26piece of information about gene
56:28susceptibility for pancreatic cancer.
56:30It's kind of flip it upside down.
56:32And what's been noticed is that if you
56:35take all individuals presenting with
56:38pancreatic cancer, about 10% of them.
56:41If you check their blood,
56:43will carry one of these genes.
56:46OK, some gene that is related to
56:48pancreatic cancer development or
56:50cancer development in general,
56:52so it'll include again bracket
56:56280 M P50P53.
56:57The APC gene in the lynch genes,
56:59so across the board a large percentage,
57:03or a sizable percentage of individuals
57:05who present with pancreatic cancer.
57:07And we're not talking about
57:08looking at the tumor itself,
57:09but looking in their blood
57:11will have an abnormality.
57:13And what's that has led to is our
57:17national guidelines changing in 2019
57:19to state that all newly diagnosed
57:23pancreatic ductal adenocarcinoma patients
57:25undergo what's called germline testing.
57:27So Dr.
57:27Lacey alluded to this earlier on.
57:29This is in addition to tumor testing
57:32and for patients who have both local
57:35disease as well as men static disease.
57:38And so, as I say, all patients now,
57:40with the diagnosis of pancreatic cancer,
57:41should be offered genetic
57:43testing regardless of their age.
57:46The patient declines testing or
57:48unfortunately dies prior to having testing.
57:50It is recommended that a first degree
57:53relative that patient is offered testing.
57:55There are multiple platforms
57:57which provide adequate testing,
57:59and they're not just limited
58:00to the bracket variance.
58:02As I say,
58:02they tent,
58:03they typically encompass a long list
58:05that I've shown you and if patients have
58:08had previous testing just for abraka,
58:10it's recommended that that
58:11be updated and it's again.
58:13Doctor Lacey alluded to positive tests
58:16also have implications for treatment.
58:19But in the early detection sphere,
58:22the concept of cascade testing is
58:24now front and center and the idea
58:26is that a patient who is presented
58:28with pancreatic cancer and who
58:31undergoes germline testing and is
58:33found to have a positive or worrisome
58:37germline mutation that that patients
58:39family or first degree relatives
58:41at least are then educated and are
58:44made to understood or understand
58:46the significance that not only
58:48is there a pancreatic cancer.
58:50In the family,
58:51but that there is likely a germline
58:54mutation and that has implications
58:56for first degree relatives.
58:58So siblings, children, parents.
59:00This is just an example of an
59:03individual with pancreatic cancer
59:05here who had a PAL B2 mutation.
59:09At least four individuals were tested
59:12123 and four up here within the family.
59:15Two of them were found to be carriers of
59:17the PAL B2 mutation and are undergoing
59:20pancreatic cancer surveillance,
59:22so this is the world of cascade testing,
59:23which you're going to hear more and more.
59:27I'd like to finish up on the final
59:29high risk category that we that we are
59:32concerned about and this is diabetes.
59:34There is a link between diabetes
59:36and pancreatic cancer.
59:38For sure individuals with longstanding
59:40diabetes has been appreciated.
59:42Our risks for developing pancreatic cancer.
59:45But there's probably a more important
59:49and significant relationship going on
59:52whereby pancreatic cancer actually
59:54results in envelops sugar abnormalities,
59:58ultimately resulting in diabetes.
01:00:01There are large number of patients
01:00:04with a diagnosis of type 2 diabetes.
01:00:07This is a late onset diabetes
01:00:10presenting in the United States.
01:00:12In fact,
01:00:13when you look at all patients presenting
01:00:16with pancreatic ductal adenocarcinoma,
01:00:18a blood sugar abnormality can be
01:00:21found in up to 85% of this group.
01:00:24Now they're not all diabetic,
01:00:25and it's probably the classic
01:00:27new onset diabetic population
01:00:29within newly diagnosed pancreatic.
01:00:31Duct adenocarcinoma is
01:00:32probably the order of 20%.
01:00:34But when you look at other ways of
01:00:36looking at blood glucose abnormalities,
01:00:38beard, advanced prediabetic stages,
01:00:40or impaired fasting glucose,
01:00:42the total number is actually
01:00:44quite a significant number,
01:00:45and some of you are probably
01:00:46familiar with this.
01:00:47Presentations of diabetes a year or two
01:00:49before a diagnosis of pancreatic cancer,
01:00:52or more difficult to control.
01:00:53Diabetes leading up to before a
01:00:56diagnosis of pancreatic cancer was made.
01:00:58When this has been studied and individuals
01:01:01have looked at patients presenting
01:01:04with pancreatic cancer and diabetes,
01:01:07we've been able to follow these patients
01:01:09back to about three years before their
01:01:12diagnosis of pancreatic cancer and being
01:01:14able to find some blood sugar abnormality.
01:01:17Now it's a very subtle
01:01:18abnormality that's there,
01:01:19and these patients didn't present
01:01:21with frank diabetes until about
01:01:236:00 or 12 months before their
01:01:25presentation of pancreatic cancer,
01:01:26but there's clearly something going on here.
01:01:29That is interesting on a
01:01:31certain kind of clinical level,
01:01:33but also provides us a very unique
01:01:35way of now trying to identify yet
01:01:39another high risk group of patients
01:01:42that we can target for surveillance.
01:01:45It's for pancreatic cancer,
01:01:46and there's a variety of
01:01:47studies underway nationally,
01:01:49but also here in Connecticut that look at
01:01:52new onset hyperglycemia and diabetes as
01:01:54a way of identifying patients with new,
01:01:59newly diagnosed pancreatic cancer.
01:02:02So in summary.
01:02:03We're not ready for general
01:02:05population screening just yet,
01:02:07but there is a lot of work going on
01:02:09with respect to trying to develop blood
01:02:11tests that would be highly accurate.
01:02:13But for now,
01:02:14we're focusing on high risk groups.
01:02:16Pancreatic cysts,
01:02:17which we've mentioned individuals
01:02:18with a family history and who are
01:02:21inheriting genes that are increasing
01:02:23risk of developing pancreatic cancer,
01:02:25and this new area of germline testing
01:02:29for affected asymptomatic family members,
01:02:32but also keep your eye on the
01:02:33area of new onset diabetes because
01:02:35it's clearly associated with an
01:02:37increased risk of pancreatic cancer,
01:02:39and we hope to be able to harness
01:02:41this to identify more patients.
01:02:43At an earlier stage.
01:02:45I will thank you for your attention
01:02:47and just leave you here with a list
01:02:50of the ongoing pancreatic cancer
01:02:51surveillance clinical studies that
01:02:53are open at Yale in the realm of
01:02:56pancreatic cysts, familial pancreatic cancer,
01:02:58and now more recently, diabetes.
01:03:00Thank you.
01:03:04Thanks doctor Farrell.
01:03:06We will close with the doctor bomb.
01:03:10Hi, let me see if I can share my screen.
01:03:45Can you guys see and hear me OK? We
01:03:48can hear you like the no screen yeah
01:03:51no screen yeah.
01:03:52Oh it didn't work OK. Will try again.
01:04:06How about now
01:04:07you're good. OK great
01:04:09so uhm. Thank you so much
01:04:12for including me tonight.
01:04:13In this talk, I'm honored to
01:04:15be here to discuss the role of
01:04:17palliative care and pancreas cancer.
01:04:21So in the next 10 minutes,
01:04:2310 to 15 minutes,
01:04:24we'll discuss the basics of what
01:04:26is palliative care conceptually
01:04:28and theoretically and what it
01:04:30is here at smilow and we'll talk
01:04:32about when is the right time during
01:04:35pancreas cancer treatment to get
01:04:37involved with the palliative care team.
01:04:39We will also discuss the common
01:04:41question of what is the difference
01:04:44between palliative care and Hospice?
01:04:46Does anyone recognize the graphic?
01:04:50They don't have audience participation
01:04:51'cause I can't see all of you,
01:04:52but that is a 7th floor healing garden
01:04:55by the hematology infusion suites.
01:05:01So palliative care is a specialized
01:05:03type of medical care which is sometimes
01:05:06called supportive oncology in the
01:05:08context of cancer care, and I think
01:05:11helps conceptualize it for patients.
01:05:13Palliative care doctors completed
01:05:15advanced specialized fellowship
01:05:16and palliative medicine,
01:05:17including how to address pain
01:05:19and symptoms and assist with
01:05:21complex medical decision making,
01:05:22prognosis and communication.
01:05:23But palliative care is usually
01:05:26provided by a whole team of providers,
01:05:28including doctors.
01:05:29Nurses, psychologists,
01:05:30pharmacists and other clinicians
01:05:32who can provide an added layer of
01:05:36support for patients and families
01:05:38facing life threatening illnesses.
01:05:40Palliative care is focused on the
01:05:42patient and their family in order
01:05:44to help provide the care that is
01:05:46best for that particular patient.
01:05:48Like I mentioned,
01:05:49palliative care is for patients and
01:05:51families with a life threatening or
01:05:53life limiting illness to support them
01:05:55through the their disease course,
01:05:57including symptom management.
01:06:00Understanding prognosis.
01:06:03And when appropriate,
01:06:04assisting with end with end of life care,
01:06:08legacy building and decision making.
01:06:17This graphic shows a view of health as
01:06:20the intersection of physical, mental,
01:06:22social and spiritual well being which
01:06:24are all part of a holistic view of our
01:06:26well being and good health as humans.
01:06:28Cancer is obviously a disease of the
01:06:31physical body, but pancreas cancer
01:06:33impacts all areas of our health.
01:06:35The approach of palliative care is to treat
01:06:37the person holistically considering the
01:06:39aspects of their treatment and well being.
01:06:41Other than fighting the cancer itself.
01:06:44That can be addressed to improve their care.
01:06:46This includes physical, mental,
01:06:48social and spiritual health,
01:06:50and it means understanding how the illness
01:06:52is impacting the patient as a person.
01:06:56In this graphic you see the palliative
01:06:59care treatment team in the center is
01:07:01the patient and family surrounding
01:07:03the patient and family and also
01:07:05working together are different
01:07:06members of the palliative care team.
01:07:08The graphic includes doctors.
01:07:10Nurse practitioners to
01:07:12spiritual care providers,
01:07:13such as chaplains and social workers,
01:07:15but there are others not
01:07:17represented in this pictorial.
01:07:21Given the big picture,
01:07:22holistic view of patient care
01:07:24and the fact that each person
01:07:26has different needs, weather,
01:07:27spiritual, physical, emotional, etc.
01:07:30The palliative care team
01:07:31is multi disciplinary.
01:07:32Multidisciplinary means that
01:07:33it's many different types of
01:07:35providers and here it's Milo.
01:07:37Like I mentioned, we don't just have
01:07:39physicians nurse practitioners,
01:07:40chaplains and social workers.
01:07:41We also have bereavement counselors,
01:07:43nurse coordinators,
01:07:44nurses, art therapists,
01:07:46pharmacists and a collaboration with
01:07:47the Yale Law School for issues related
01:07:49to custody or legacy or other legal.
01:07:52Issues that arise when facing a life
01:07:54limiting or life threatening illness.
01:07:56We have inpatient and outpatient
01:07:58palliative care available and the
01:08:00outpatient is for oncology patients only.
01:08:02For cancer patients only,
01:08:04but that includes logitudinal follow
01:08:06up with the with the palliative
01:08:08care interdisciplinary team.
01:08:12So the Yale Palliative Care services
01:08:16just to detail that a little more
01:08:19specifically includes an inpatient konsult
01:08:21service for both adults and children.
01:08:24Pediatric patients for
01:08:27cancer and non cancer teams.
01:08:30And then in the outpatient it includes
01:08:33cancer only outpatient konsult service
01:08:36which has scheduled clinics Mondays
01:08:39through Fridays and is available
01:08:40at both New Haven and North Haven.
01:08:43So that's part of care can be provided
01:08:46in the hospital as a konsult service or
01:08:48in the outpatient setting as a konsult
01:08:51service at the same site as your as
01:08:53your visit with your oncology team.
01:08:56In the future home based palliative care may
01:08:58also be an option depending on insurance,
01:09:01but it's not yet available as
01:09:02the standard treatment at SMILOW.
01:09:07Nope, sorry, there we go.
01:09:10So the question we now turn to is when
01:09:12is it appropriate to involve palliative
01:09:14care and pancreas cancer treatment?
01:09:17Here you see two graphics on
01:09:19the cancer care continuum.
01:09:22That means the way that
01:09:24cancer is treated overtime.
01:09:25The first shows an old-fashioned
01:09:27model of palliative care where
01:09:29palliative care is simply used as it
01:09:32transitioned to end of life care or
01:09:34Hospice care in a in a disease that
01:09:36is no longer responding to disease,
01:09:38modifying or life prolonging treatments.
01:09:41However, research has shown that
01:09:44patients with cancer benefit from
01:09:46earlier integrated palliative care,
01:09:48particularly with challenging
01:09:50diseases like pancreas cancer.
01:09:52Thus, now we can say that
01:09:54palliative care is for any age,
01:09:55patient, and any stage of disease,
01:09:57including patients with palliative with
01:10:00pancreas cancer with curative intent,
01:10:02treatment plans.
01:10:04Palliative care is there to support
01:10:05the patient and family through
01:10:06a life threatening illness.
01:10:07In this case their pancreas cancer journey.
01:10:10And when the treatment plans are
01:10:12currative to support them through the
01:10:14process of their pain and symptoms
01:10:16and other decision making with
01:10:18treatment plans that aren't caritive
01:10:20that treatment goals may change
01:10:22overtime and the role of palliative
01:10:24care can also change overtime.
01:10:26The palliative care team may
01:10:27step in more or less to help with
01:10:29symptoms and improve quality of
01:10:30life depending on the current needs
01:10:32of the patient and family.
01:10:40That brings us to the next question.
01:10:43What is the difference between
01:10:45palliative care and Hospice care?
01:10:47When the disease does continue to
01:10:49progress or the treatment stopped,
01:10:51working patients with pancreas cancer
01:10:52may begin to face discussions and
01:10:55decisions about end of life care.
01:10:56One question that frequently arises
01:10:58in my experience is what is Hospice
01:11:01and what is the difference between
01:11:03palliative care and Hospice?
01:11:05It's important to understand the end of life.
01:11:08Care is one component of palliative care,
01:11:11and that includes Hospice but
01:11:13not all palliative care.
01:11:14Treatment is focused on end of life.
01:11:16Palliative care may be provided
01:11:18at the same time as chemotherapy,
01:11:20disease, directed treatments,
01:11:22surgical interventions,
01:11:23and life prolonging therapies.
01:11:25Hospice, on the other hand,
01:11:27it's focused purely on symptom management
01:11:29and comfort care at the end of life.
01:11:31Palliative care and Hospice both
01:11:33share a common goal of alleviating.
01:11:35Distress enhancing quality of
01:11:37life but take place at different
01:11:39times in the disease course.
01:11:46Here you see a different graphic
01:11:48again of the cancer care continuum,
01:11:50but this is the graphic of
01:11:52the cancer continuum from
01:11:53the perspective of Hospice.
01:11:55So what, then is Hospice?
01:11:56And who should consider it?
01:11:58Hospice care for patients
01:11:59and families at end of life.
01:12:03In this graphic we again see the
01:12:05palliative care integrated and growing
01:12:07in its role and its importance while
01:12:10disease directed therapies such
01:12:11as chemotherapy are being given,
01:12:13but in the purple you see
01:12:15the transition to Hospice,
01:12:16and in this Hospice care graphic
01:12:18you also see a new stage of cancer
01:12:21when cancer is not cured and is
01:12:23terminal which is the bereavement
01:12:25stage and includes the family.
01:12:28Hospice care focuses on the patient who
01:12:30is no longer benefiting from cancer
01:12:32directed therapies such as chemo or surgery,
01:12:35and focuses on supporting the patients
01:12:37comfort at the end of their life.
01:12:39This can be ours today's days,
01:12:42to weeks or weeks to months.
01:12:43Hospices us a philosophy of care
01:12:46focused on patient comfort,
01:12:48dignity in quality of life,
01:12:50and helps patients to navigate
01:12:51the end of their lives.
01:12:55The Hospice services can take place at
01:12:58home in the hospital or in a facility,
01:13:00and this brings me to my second point,
01:13:02that Hospice is truly two things.
01:13:04It is a philosophy of care,
01:13:05as you see detailed on this slide.
01:13:11But it is also an insurance benefit
01:13:14that provides specific levels of
01:13:16care and specific services to
01:13:18eligible patients, eligible patients,
01:13:20or those with a life expectancy critic
01:13:23did to be less than six months.
01:13:25If the disease is allowed
01:13:26to run its natural course.
01:13:28In that sense,
01:13:29it is important to know that Hospice
01:13:31is a covered financial benefit that
01:13:33normally is given in the home and
01:13:35includes connections to nurses on
01:13:36call to call with questions some small
01:13:38amount of assistance in the home and
01:13:41support such as medications, hospital.
01:13:42But in the house or other home
01:13:45safety adaptations, however,
01:13:46it is rarely 24 hour care except under
01:13:49short term limited conditions and
01:13:51the burden of the 24 hour care still
01:13:53remains on the family or private pay.
01:13:58Patients with pancreas cancer will
01:14:00potentially benefit from Hospice at different
01:14:02times in the course of their disease,
01:14:04depending on their treatment options.
01:14:06Depending on their personal needs.
01:14:08Depending on their goals of care,
01:14:10each person is different and one goal
01:14:12of palliative care of the palliative
01:14:14care team and palliative care in general
01:14:16is to help patients and families
01:14:17navigate these types of decisions,
01:14:19such as wind to enroll in
01:14:21Hospice when the time arises,
01:14:22and this is also an important role of the
01:14:25oncologists over the course of the illness.
01:14:27To help the patient with decision making.
01:14:29About disease, directed therapies.
01:14:31Persons comfort measures.
01:14:33And this brings me to my final
01:14:35point of this of this talk.
01:14:37The goal of providing palliative care
01:14:39it's of people with pancreas cancer
01:14:41is to provide patient centered care.
01:14:43The goal of palliative care and oncology
01:14:45treatment teams is to provide the
01:14:46patient with the care that is right for
01:14:48them that is individualized and that
01:14:50aligns with their goals and values.
01:14:52Part of that can be helping patients
01:14:54and families understand their disease,
01:14:56understand their treatment options,
01:14:58and understand their expected outcomes.
01:15:00It can be supporting their symptoms
01:15:01and treating their pain, and it can be.
01:15:04Providing us.
01:15:05Emotional support to the patient and family.
01:15:07Of course,
01:15:08this can and will change overtime
01:15:10for each individual person,
01:15:12and it's important to have an open and
01:15:14ongoing communication and discussion
01:15:15between patients and their medical
01:15:17teams as to what the current course
01:15:20of treatment and future looks like.
01:15:23And that concludes my section.
01:15:25Thank you very much.
01:15:28Thank you Doctor Baum for educating
01:15:30us on the personalized holistic
01:15:32approach to care that we pursue here
01:15:34at Smilow will get started with the
01:15:37question and answer session now
01:15:38and maybe I'll start with one of
01:15:40the questions for Doctor Farrell.
01:15:41How does someone get involved in
01:15:43genetic testing for pancreatic cancer?
01:15:46Does your oncologist make a referral?
01:15:48Is testing done during chemotherapy
01:15:49or afterwards?
01:15:51OK, thanks for that question.
01:15:53So I think it's important to start by
01:15:56saying for the purpose of terminology
01:15:58there are two types of genetic testings.
01:16:02There's testing on your blood and
01:16:04there's testing on your tumor.
01:16:06Both are typically initiated
01:16:09by the oncologist.
01:16:11The oncologist for certainly when they're
01:16:12trying to come up with management plan,
01:16:14would request that the tissue the
01:16:17tumor be tested for mutations,
01:16:19which again Dr Lacy alluded to.
01:16:22The issue of germline testing
01:16:24whereby your blood is tested to look
01:16:27for those inherited genes is also
01:16:29typically initiated in that setting
01:16:31after a diagnosis by the medical
01:16:34oncologist and the patient is referred
01:16:37to the cancer genetic services.
01:16:39Here at smilow they then undergo
01:16:42formal cancer, genetic counseling.
01:16:43Blood tests are ordered and then
01:16:45when the results come back they're
01:16:47shared both with the oncologist
01:16:49as well as the rest of the team.
01:16:51So those are two different strategies.
01:16:53Whereby a patient would end up with
01:16:56genetic testing for family members
01:16:58who are concerned about their risks.
01:17:01They can also seek out the cancer
01:17:04genetic services to inquire about
01:17:05the risks and also now that we
01:17:07have specific disease,
01:17:09specific clinics such as pancreas
01:17:11and breast as well as colon
01:17:13cancer for individual cancers.
01:17:15Great
01:17:16yeah we had a question in the chat and
01:17:18one in the Q&A about chemotherapy.
01:17:20Maybe I'll refer this to Doctor Lacy.
01:17:23There's a question about how
01:17:24many cycles of chemotherapy or
01:17:26given what are the side effects,
01:17:27and are there any new pills that
01:17:29could target the tumor site only to
01:17:31avoid some of those side effects?
01:17:34Thank you for that great
01:17:35question. You've hit some of the
01:17:37really key aspects of chemotherapy
01:17:39treatment for our patients,
01:17:42so I mentioned full fear knocks a lot in
01:17:45my talk because I think it has probably
01:17:48had the greatest impact on improving
01:17:51outcomes in terms of Survival II.
01:17:55Also mentioned is at some expense.
01:17:57Spence, with respect to side effects,
01:17:59so with regards to full fernox
01:18:01for patients who are operable and
01:18:03surgery is a part of their overall.
01:18:06Management plan the recommended
01:18:08duration of chemotherapy is six months,
01:18:11which which translates into 12 cycles.
01:18:14We do treatment every other week,
01:18:16so about two treatments a month.
01:18:18There is some emerging data
01:18:20that the duration matters,
01:18:22that patients who get all 12 cycles,
01:18:26even if there are some delays
01:18:28and dose reductions,
01:18:29do have a higher cure rate an and.
01:18:32So we really aim to achieve that goal.
01:18:36In some cases we will be giving
01:18:38the chemotherapy before surgery,
01:18:40depending on whether there's
01:18:41a need to do that.
01:18:42Usually that's driven by
01:18:44vascular involvement,
01:18:44or in some cases some chemotherapy
01:18:48before in some chemotherapy afterwards,
01:18:51full fernox is, is or can be.
01:18:54It's not in all patients a tough regimen,
01:18:57their common,
01:18:58and it is a little bit involved
01:19:00because patients have to be in
01:19:01the office for at least a good
01:19:03half a day to do the treatment.
01:19:05It's three chemo drugs plus a vitamin.
01:19:06They have to be infused and it takes
01:19:09awhile along with the pre medications
01:19:11for nausea and then when they leave
01:19:13the office they will continue to have
01:19:15one of the drugs infusing with the
01:19:17home portable infusion pump for two
01:19:19days so it's a little bit cumbersome
01:19:22and I do know that patients get tired
01:19:24of coming into the clinic every
01:19:26other week to get full fear knocks.
01:19:28In terms of side effects,
01:19:29if it is,
01:19:30it is highly variable and I have
01:19:34yet to identify those patients who
01:19:35will sail through it and those
01:19:37patients who will struggle.
01:19:38In general,
01:19:39we say that older frailer patients will have
01:19:41a more difficult time and more toxicity,
01:19:43and I think that is true,
01:19:45but other than that it's actually
01:19:47quite difficult to really identify
01:19:49in advance what we're going to
01:19:51encounter in each individual patient.
01:19:53Common side effects are feeling tired,
01:19:55ultra taste,
01:19:57some nausea, queasiness.
01:19:58Which we can manage usually quite well.
01:20:03So an odd side effect of this regimen is
01:20:06something we refer to as cold sensitivity
01:20:08every time the patient touches something
01:20:10or drink something cold, they get in
01:20:14very unpleasant obnoxious sensation,
01:20:16and none of the side effects are serious,
01:20:18but they affect quality of life.
01:20:20There are a few serious side effects.
01:20:22One's risk of infection.
01:20:23That risk is quite low with the
01:20:26supportive care that we have,
01:20:27but still infection in the setting of
01:20:30chemotherapy can be serious rhythm,
01:20:32life threatening.
01:20:33And the other a serious side
01:20:35effect is severe diarrhea,
01:20:37which can happen in about 5% of patients.
01:20:39Some patients don't have
01:20:41serious side effects,
01:20:42they just kind of feel crummy all the
01:20:45way through so you know it is a bit of
01:20:47a Pyrrhic victory with full fear knocks.
01:20:49And you know,
01:20:50we wish we had an easier regimen,
01:20:51both in terms of administration
01:20:54and side effects.
01:20:56Gemcitabine and abraxane.
01:20:59So let me let me pivot back to the other
01:21:02part of the question is duration so.
01:21:04For resectable disease, at six months,
01:21:06for patients who have.
01:21:09Incurable advanced disease in
01:21:11pancreas cancer.
01:21:13We generally prefer not to just stop all
01:21:15the drugs and take a chemotherapy holiday,
01:21:18'cause the likelihood of the disease
01:21:21becoming active again quickly is high,
01:21:23but it is difficult to be on a regimen
01:21:25like filthy rhynocs indefinitely,
01:21:27so we will tend to modify the regimen
01:21:30as we go along and withdraw drugs to
01:21:34make it more palatable for patients.
01:21:36The other regimen gemcitabine and ABRAXANE,
01:21:38is easier.
01:21:39In the sense that there is
01:21:42typically A and not the NADA.
01:21:47And the diarrhea.
01:21:48So the GI side effects.
01:21:50The gastrointestinal side
01:21:51effects are much less prominent.
01:21:53There still is the fatigue
01:21:55and the risk of infection.
01:21:57There is a more hair loss
01:21:59with gemcitabine ABRAXANE.
01:22:00I think which is definitely an
01:22:01issue for a lot of patients.
01:22:03So again, these have made a difference,
01:22:05but they are not the easiest regiments.
01:22:07There's no question about that.
01:22:10And then the second part of the question is,
01:22:12are there ways of making these
01:22:14drugs target more specifically the
01:22:16tumor and not the other other sites?
01:22:18Maybe I'll jump in here and say that this
01:22:20is clearly an active area of research.
01:22:22We would love to minimize side effects
01:22:25and maximize effect on the tumor,
01:22:27and there are several approaches that are
01:22:29being currently tried in preclinical studies.
01:22:31So prior to getting to the clinic as
01:22:34well as in in clinical studies to mix
01:22:36drugs into particular nanoparticles.
01:22:39So small particles that.
01:22:40You can put various things on the surface
01:22:43to try and direct it more specifically
01:22:45to the tumor cells and other approaches
01:22:47to conjugate these drugs to specific
01:22:50proteins called antibodies that can
01:22:53detect particular other proteins that
01:22:55are specific to our the tumor cells,
01:22:58and perhaps would lead to less
01:23:00side effects to normal tissue.
01:23:02So it's clearly an active air investigation
01:23:06to try and improve tumor specific
01:23:08targeting and to minimize side effects.
01:23:11Uh, maybe we'll move to the next
01:23:14question for Doctor Farrell.
01:23:16What percentage of pancreatic cancer
01:23:17patients have no identifiable risk factors?
01:23:22So I focused on in the talk more on
01:23:25the familial or genetic aspects of it,
01:23:28and the reality is, is that the majority
01:23:30of patients presenting with pancreatic
01:23:32cancer do not have those risk factors?
01:23:34They don't have an identifiable
01:23:36strong family history, or when you
01:23:38go looking for a germline mutation.
01:23:40One of those mutations,
01:23:41and so we consider this group to be sporadic.
01:23:45But there are of course a whole
01:23:46bunch of lifestyle issues that
01:23:48may increase your risk for it,
01:23:49so smoking we alluded to.
01:23:52Beasty is certainly a factor in their race
01:23:56is also being considered risk factor.
01:23:58With African Americans having an increased
01:24:01risk of developing pancreatic cancer,
01:24:03the idea of course that there are
01:24:05people who don't have obvious risk
01:24:07factors developing pancreatic cancers.
01:24:09Unfortunately,
01:24:09we see this and it can be quite.
01:24:12It can be quite alarming to try
01:24:14and understand exactly what were
01:24:16the factors in play here,
01:24:17probably related to issues of microbiome or
01:24:20some other environmental exposure issues so.
01:24:22Uhm again, it's about 10,
01:24:24maybe to 15% that either have a familial
01:24:27and or a genetic risk factor that we can
01:24:30test for for the remainder of individuals.
01:24:33A fair percentage have
01:24:35identified risk factors,
01:24:36but yes,
01:24:37there is a percentage of
01:24:38individuals who when you go asking,
01:24:39do not have a clearly identified
01:24:42risk factor for pancreatic cancer.
01:24:45And
01:24:46then we have another chemotherapy question.
01:24:47Uh, I think best referred to Doctor Lacey.
01:24:49What percentage of your patients develop
01:24:52resistant resistance to full pronox?
01:24:54And after how many infusions?
01:24:58Right, so here we're talking about
01:25:01patients with advanced disease.
01:25:03Either locally advanced,
01:25:04unresectable, who are not going
01:25:07into surgery or metastatic disease.
01:25:09And you know these both of these groups.
01:25:15Will eventually stop
01:25:17getting benefit from Fernox.
01:25:20There we will see that the tumor is
01:25:22progressing and the tumor markers are
01:25:24going up and we will conclude that the
01:25:27chemotherapy is no longer working,
01:25:29so those patients have developed resistance.
01:25:32There are many complex mechanisms that are
01:25:35involved, some of which we understand,
01:25:36many of which we don't,
01:25:38but it is inevitable, really.
01:25:41In the vast majority of patients
01:25:43that at some time at some point.
01:25:45The chemotherapy will stop working.
01:25:48So the average time it you know I I
01:25:52don't like these types of numbers
01:25:53because no patient is an average
01:25:55and it is all over the map.
01:25:56But in the clinical in the initial
01:25:58clinical trial of Fear Knocks.
01:26:00That was presented in 2011.
01:26:03It was about five to six months come
01:26:07before patients develop resistance
01:26:09with the chemotherapy stopped working.
01:26:11But I would say that there's there's
01:26:14a very significant percentage of
01:26:17patients who derive benefit from
01:26:19this regimen much longer than that,
01:26:20and I I have had patients on full
01:26:23fear knocks and then transitioning
01:26:25to a maintenance regimen for a
01:26:27couple of years so it is hard to
01:26:29draw conclusions from some of those
01:26:31averages for an individual patient.
01:26:35And we're getting running short on time,
01:26:36so maybe I'll ask the last
01:26:38question to all of you and
01:26:40maybe start with Doctor Salem.
01:26:41What are you hopeful for
01:26:44for pancreatic cancer care?
01:26:45I want in the future.
01:26:54So that's really a good
01:26:56question, you know. Pancreas
01:26:58cancer is just been difficult in
01:27:00in in so many different ways.
01:27:03You know the diagnosis differs difficult.
01:27:05The radiology is difficult.
01:27:06The surgery is difficult to chemotherapy,
01:27:08is difficult, nothing is.
01:27:11Easy about pancreas cancer, but really,
01:27:14I think what you've heard today is
01:27:16the improvements in chemotherapy.
01:27:19You've heard about the
01:27:21improvements in early diagnosis.
01:27:23Heard about the identification of
01:27:25genetic markers that can help us
01:27:28and really also of course the most
01:27:30important you know palliative care
01:27:32'cause so many of our patients
01:27:34do require that essentially.
01:27:35So what I would hope for really is
01:27:38improvement in all of these areas
01:27:39and I think all of these areas
01:27:42show promise and I think that's
01:27:44what makes it exciting for us.
01:27:46And you know,
01:27:47the challenge is not insurmountable
01:27:48and I do believe that in all of
01:27:50these areas we will see progress
01:27:52over the next decade.
01:27:54Doctor Baum
01:27:57uhm? So it's a good question since I
01:27:59gave the palliative care talk maybe
01:28:01I'll say a non palliative care answer,
01:28:04which is that I always think
01:28:06about and I'm not very old.
01:28:08As you mentioned I'm the most junior
01:28:10person here so when I was in residency
01:28:12at NYU there was a physician,
01:28:14a medical oncologist who did all of
01:28:17the treatment for the metastatic
01:28:19Melanoma patients and I thought,
01:28:22Oh my God, who would want to do that?
01:28:25It's such a difficult disease.
01:28:26They do so poorly,
01:28:28and then there's been really,
01:28:30truly disruptive innovation.
01:28:31Really huge developments where we
01:28:34see metastatic Melanoma patients
01:28:37being cured with novel therapies,
01:28:39and I think that.
01:28:41For pancreas cancer,
01:28:43what has to happen in our lifetime
01:28:46and soon as some kind of big new
01:28:50way of thinking and and scientific
01:28:52change that that we don't see
01:28:55coming and that makes this a
01:28:58more easily treatable cancer?
01:29:00I think that is the real
01:29:01way to think about that.
01:29:03There's things that we don't
01:29:04know about yet and that they're
01:29:06scientists working on it.
01:29:07And then,
01:29:08uhm,
01:29:08I do hope that with patients who are
01:29:11currently dealing with pancreas cancer
01:29:13that we will be able to give them
01:29:16the treatment that is best for them,
01:29:18and that that gives them the
01:29:21best outcomes possible under
01:29:22the current circumstances.
01:29:24Doctor Farrell
01:29:27you know when I go back and look at things
01:29:30that I wrote about pancreatic disease.
01:29:3210 in 10 or 15 years ago and I I realized how
01:29:36much in the dark ages we were and how much.
01:29:40Progress has been made at least in
01:29:42our understanding of diseases were
01:29:44a lot more sophisticated about.
01:29:46We think about it, there's been a lot
01:29:49of exciting research in this area,
01:29:51and so it's slow and sometimes the
01:29:54applications to patient care to improve
01:29:56patient outcomes and quality of life are
01:29:59slow, but they are actually happening,
01:30:02and I think that's where I kind
01:30:03of take a lot of solace from.
01:30:06This is a long game.
01:30:07This is not a Sprint.
01:30:08This is a marathon for all of us.
01:30:10Specially our patients, and so you know,
01:30:12I'm optimistic that we're going
01:30:14in the right direction.
01:30:16Yes, it's going to take some other major
01:30:18achievements that have to be made,
01:30:20but when I look back and see where
01:30:22we've come from and what we have gained
01:30:24over the last five ten years ago now,
01:30:26I mean not just in the diagnostics,
01:30:27but even in the therapeutic area.
01:30:30And I'm optimistic for the future
01:30:32and for our patients.
01:30:35And will doctor Lacey will
01:30:36give you the final word.
01:30:38Oh well, thank you everyone
01:30:40for your comments.
01:30:41'cause you have basically expressed
01:30:45my thoughts. So what's left?
01:30:48So what's on my wish list for this
01:30:52disease is a prevention strategy.
01:30:55We know that there's a very long
01:30:57latency period where those pancreatic
01:31:00ductal cells are undergoing changes.
01:31:02Their premium plastic,
01:31:03sort of analogous to the polyp in the colon.
01:31:06It takes 10 years to turn into
01:31:08a cancer now for colon cancer.
01:31:10We can remove the polyp.
01:31:12It's not so simple in the pancreas,
01:31:13but if we could identify a medication
01:31:16that has as few side effects and is.
01:31:19Effective in reversing some of those changes,
01:31:21I mean that changes that would be that
01:31:23would be for me the most incredible
01:31:26breakthrough for this disease.
01:31:28Of short of that, I'm getting back to.
01:31:32We are.
01:31:32We are new early diagnosis patients
01:31:34present with advanced stage disease.
01:31:36You know we need the kind of breakthrough
01:31:38they had in the Melanoma field.
01:31:39As, as Laura alluded to,
01:31:40is that kind of come from immunotherapy.
01:31:42I think many of us think so because
01:31:44that's where the major breakthroughs
01:31:46have come with other diseases.
01:31:47But we may be surprised.
01:31:49Maybe some of these other strategies
01:31:51or combinations of strategies
01:31:53will give us that giant leap
01:31:54forward that we're all hoping for.
01:31:57Great, so it's clear that clinical care
01:31:59is slowly improving in pancreatic cancer,
01:32:01and I think, as everyone alluded to,
01:32:03research is hopefully gonna make major
01:32:05breakthroughs in the coming years.
01:32:07And so on. That hopeful note.
01:32:08I want to thank our speakers for their
01:32:11insightful comments and educating us today,
01:32:13and also thank all of you
01:32:15at home for your attention.
01:32:17Have a great evening.