Information Session: Pancreatic Cancer

Corporate Speakers:

• Jeffrey Drebin; Memorial Sloan Kettering Cancer Center; Chair of the Department of Surgery
• William Jarnagin; Memorial Sloan Kettering Cancer Center; Chief, Hepatopancreatobiliary Service
• Eileen O'Reilly; Memorial Sloan Kettering Cancer Center; Section Head, Hepatopancreaticobiliary and Neuroendocrine Cancers
• Chris Crane; Memorial Sloan Kettering Cancer Center; Radiation Oncologist
• Christine Iacobuzio-Donahue; Memorial Sloan Kettering Cancer Center; Director, Pancreas Cancer Research
• Robin Brenner; Memorial Sloan Kettering Cancer Center; Clinical Trials Nurse

PRESENTATION

Operator:  Good afternoon and welcome to this Memorial Sloan Kettering information session on pancreatic cancer. 

Our host and moderator for today's call is Dr. Jeffrey Drebin.  Chair of the Department of Surgery at MSK.  I will now turn the call over to Dr. Drebin.  Please go ahead. 

Jeffrey Drebin:  Good afternoon and welcome to this Memorial Sloan Kettering Cancer Center Pancreas Cancer Information Session.  We have a multidisciplinary panel of experts who will address questions that have been previously submitted.  To give you a little background on myself, I'm the Chair of the Department of Surgery here at Memorial Sloan-Kettering and I'm also a surgeon who specializes in pancreas cancer. 

We thank you for joining this call.  We want you to know that Memorial Sloan-Kettering is working hard to keep you and your loved ones safe when you come for an appointment or treatment at any of our locations.  Pancreas cancer has been in the news a lot lately. 

Today, with our panel of experts, we'll answer some of your questions that were shared in advance of the call.  We'll try to get to as many of these questions as possible. 

I want to remind you that our Memorial Sloan-Kettering doctors and care teams are ready and willing to talk to you directly about your concerns and I encourage you to reach out to them to discuss next steps in your care and to ask them many questions that do not get answered on a call here today. 

QUESTIONS AND ANSWERS

Jeffrey Drebin:  I want to start off with a question that addresses the whole issue of cancer care and cancer screenings during this time when COVID has dominated the news.  And certainly, COVID is a frightening syndrome which is flaring throughout the region and throughout the nation. 

But it is critical to remember that cancer kills many more people than COVID and cancer screening, for many forms of cancer, is highly effective at identifying cancer early at a time when treatment is more effective.  We will talk a bit later about pancreas cancer screening which unfortunately is that an earlier stage. 

But things like colon cancer, breast cancer, prostate cancer, cancer of the uterine cervix and lung cancer can be identified at a more curable stage if it's identified early and during the spring when the COVID pandemic first blossomed in the region.  Screenings dropped 80-90% and it's critical that patients, particularly those in high risk groups get those screenings so that they can find their cancers at a time when they're curable. 

All institutions, led by ours but including other major centers around the region are doing everything possible to keep patients safe from COVID infection including screening of patients and staff which should markedly decrease, if not almost completely eliminate the risk that a patient would become infected in the process of obtaining care. 

I'm going to shift gears there because pancreas cancer is really why our listeners are on the line, I'm sure, and we had a lot of questions about the latest treatment advances for pancreas cancer and I'm going to ask Dr. William Jarnagin who is chief of the hepatopancreatic or biliary surgery service and also a very experienced pancreas cancer surgeon. 

Bill, can you talk about what the surgical treatment of this disease involves? 

William Jarnagin:  Yes, Jeff.  And thank – thanks for having me on the panel.  So, surgery for pancreas cancer is generally involves removal of the tumor with part of the pancreas and some of the surrounding tissue or organs that are involved. 

For the most part, this consists of two different types of operations.  One is called the Whipple operation or pancreaticoduodenectomy and this is done for tumors that involve the head of the pancreas or the proximal pancreas as it sometimes is called. 

This is a fairly involved operation that requires removal, not only of the head of the pancreas but also the first part of the intestine called the duodenum, the lower part of the bile duct and the gallbladder if not been removed previously.  And then there's a reconstruction of those structures into the – into the small intestine. 

So, it's fairly involved and it does involve a rear – reorganization to some degree of the upper abdominal organ.  The other operation that’s commonly done for this is called the distal pancreatectomy with a splenectomy, typically, or a left-sided pancreatectomy. 

This is done for tumors that involve the body or tail of the pancreas and involve removing a part of the pancreas as well – as well as the spleen.  These operations, especially the distal pancreatectomy are done – well, they're both done as open operations, meaning traditional incision. 

But increasingly, we're using minimally invasive techniques to do these procedures of the – and that’s being done in greater frequency.  Not so much for the Whipple operation but that is starting to happen a bit more slowly. 

Jeffrey Drebin:  Thank you, Bill.  We have a sort of parallel question talking about the advances in treatment from a medical oncology perspective.  Dr. Eileen O'Reilly who is head of the section of Hepatopancreaticobiliary and Neuroendocrine Cancers at Memorial Sloan-Kettering is on the line. 

Eileen, can you talk about advances in treatment from a medical point of view? 

Eileen O'Reilly:  Sure, Jeff.  Thank you very much and thank you all for joining this afternoon. 

Yes.  So, I think we're seeing some definite progress in pancreas cancer over the last decade.  One of the main phase of treatment is combination chemotherapy and when we look back compared to a period of time ago, treatments are working better for longer, for a given individual, but we clearly need to build on the current standards. 

And one of the important understandings regarding pancreas cancer is the genetic context of the disease.  So, by that, we mean whether a person has a predisposition to developing pancreas cancer and this sort of goes back to the topic of screening, but it also – also intersects with the topic of personalized medicine or precision medicine being able to refine a treatment strategy for a given individual. 

And to give an example there, the BRCA genes, BRCA genes are known for their association with breast and ovary and prostate cancer, but they're also very important in pancreas cancer and may account for about five or six or 7% of people who've been diagnosed with this disease.  But they also underpin specific treatments such as platinum drugs which are part of folfirinox  for example, that’s one of the combination of chemotherapy treatments that’s used. 

And also informed the use of [class] drugs called PERK inhibitors which is an oral class of medications that is now FDA-approved and established as a maintenance treatment for pancreas cancer. 

So, for everybody who is diagnosed with this disease and these are recent guidelines, we recommend genetic screening in terms of looking at the family bloodline to see if there's any genes related to the development bankers cancer, but we also do a parallel detailed analysis on the tumor itself. 

And the integrated findings from both of those informed whether they're replications for a person's family, but also can guide specific treatment strategies.  And there are small subsets of genetic findings for which there are drugs now that we use on the clinic on an everyday basis. 

So, the hope is to be able to refine these treatments even more and to be able to, for some degree, to get away from chemotherapy, although that’s not happening in the – in the short time, but there's certainly glimpses of how to do this on an individual person basis. 

Jeffrey Drebin:  Thank you, Eileen.  There's another question here about radiation therapy.  Radiation therapy as a mode – important and sole modality is often used and even more in combination with chemotherapy or – and/or surgery. 

Chris Crane is a radiation oncologist who specializes in pancreas cancer radiation therapy.  Chris, can you talk about – about some of our advances in radiation therapy? 

Chris Crane:  Yes.  Thank you, Jeff, again, for having me on the panel as well.  I think just briefly, the role of radiation and the preoperative setting for someone who has a potentially respectable cancer is, I think that’s individualized.  I think you have that the jury still out about whether it should routinely be given.  But it does seem to help with margin negative resection. 

There are two ways to think about radiation, are palliative and adjuvant or neoadjuvant dosing which, again, would be something traditionally that would help with (inaudible) resection or historically had been given with the intent of prolonging survival or improving symptoms. 

Now, we are able to give [higher doses] of radiation with specialized techniques.  My colleagues and I have been working on this for close to 15 years and now have a pretty mature approach to giving high dose radiation which is twice the adjuvant and palliative dose. 

This is something that is pretty much universal in the (inaudible) oncology is that there's a dose response that lead to better tumor control, if you can get over certain threshold, we call it ablative radiation.  And we think that we've – based on our very significant numbers now, I think that there is a median survival benefit and a two and three-year survival benefit that’s due to controlling the tumor better, we still have work to do to improve on that. 

But it is something that we think it is a step forward and it can be – it's done very safely.  The only risk is very minor, small 3% or so, 3-8% rate of bleeding that results with transfusion and healing as basically from gastritis.  The challenge of giving these doses of radiation is that the organs move from day-to-day and they move with breathing. 

So, you have to have – the clinicians have to have solutions for those problems in order to give the treatment safely.  And since we're fortunate to have such a great physics department and a large department with a lot of different kinds of resources, we can pull those pieces together and deliver this treatment across our entire network. 

So, we treat more patients with this treatment out in New Jersey and Long Island than we do it at the main hospital.  That’s all standardized and delivered there as well. 

Now, I think that the next steps moving forward, I think that this particular treatment is probably not to be getting any better, but we can combine it with immunotherapy, potentially, and we do have a trial for that, that's seeking to perhaps synergize with radiation with a drug called durvalumab which is approved and was approved, actually, in the high-risk adjuvant setting in lung cancer. 

So, we have a trial that’s trying to [implicate] that – that success.  They try to address the [distant] metastatic component of treatment. 

Now, the other – the other thing to mention is that ablative radiation can now be given in five treatments.  And that is with the technology that we are leading the way in as well, which allows the radiation planning to be duplicated in one hour while the patient's on the machine. 

So, that addresses the organ motion component in real time as opposed to taking five weeks to do the plan which is the normal way.  So, this just basically, for us, it enables us to do the treatment in a much more convenient way in five treatments. 

Jeffrey Drebin:  All right.  Well, let's – let's move along.  We sort of had touch based – Eileen mentioned the fact that there is a genetic component to pancreatic cancer in many patients.  And on the call, we have Christine Iacobuzio-Donahue who's director of the Memorial Sloan Kettering Center for Pancreas Cancer Research. 

Christine, many of our listeners are very concerned about cancer genetics and whether there's a familial risk and what we know about the genes responsible for pancreas cancer.  Can you handle that one? 

Christine Iacobuzio-Donahue:  I can.  Thank you, Jeff.  I appreciate being on this panel with my colleagues. 

So, there is a bright side of looking after genetic aspects of pancreatic cancer is that it's information that we can learn, that we can do something about. 

So, for example, if you take just unselected populations of patients, just all [comers] that come in and if you sequence their normal DNA, just to see what is their constitutional makeup, as much as 20% of patients may have a mutation and the most common mutation that may be seen is in BRCA 2 or related genes BRCA 1 and PALB2 and that’s important because that is, as Eileen was saying, that it's actionable.  That makes tumors responsive to particular treatments. 

But those mutations can also recur in the tumor-specifically and not in the germline.  So, that is something that we can act on – act on with respect to pancreas cancer.  We are learning, with respect to the genetics, that usually, there are four genes that are very commonly mutated in pancreas cancer, those as KRAS, p53, CDKN2A and SMAD4. 

But not everybody has a mutation in those genes and 5%, maybe upwards, getting close to 10% of patients do not have a KRAS.  We are finding those patient have alternative mechanisms of actuated – activating cellular pathways that a KRAS mutation normally would. 

And again, those are actionable.  For example, there's data coming out that some patients that have a KRAS wild-type tumor can have a fusion in the – in a gene called NRG1 and that is certainly targetable.  So, this is, again, something that is present about 1% of people but it is something that we can do. 

So, with respect to the germline, for most patients who have a family history, we will not be able to find a genetic explanation.  That doesn’t mean there isn't one but I think family history is always the most important aspect about getting a sense of how the patients – what their [pre decision] may be. 

So, that’s where we are right now that we – like Eileen said, we certainly advocate for a germline testing on every patient in the event that we do find something.  And in some patients, we will find something that’s actionable and it's important to know your history and advocate for yourself, I think, and tell your doctor.  And you know we definitely advocate for germline testing. 

Jeffrey Drebin:  Thank you.  Thank you, Christine.  It's very helpful. 

So, that leads to the whole issue of clinical trials.  There are all sorts of innovative compounds being tested, specific targeted agents, sometimes immunotherapies or other very innovative trials. 

And we have – one of our clinical trials nurses, Robin Brenner, who's been involved in helping a large number of patients on to clinical trials at MSK.  Robin, can you talk about how patients are maybe evaluated for trials in and how patients can find out what their options are? 

Robin Brenner:  Yes.  Thank you, Jeff.  First, let me just acknowledge that as everyone is hearing right now, it's very exciting time and a very hopeful time for researching pancreas cancer and the privilege to be part of this team and of our patients who are participating in clinical trials. 

There's a myriad of treatments for every stage of pancreas cancer as we're going to hear and have heard, patients who have surgically resectable disease, borderline resectable, locally advanced pancreas cancer and pancreas cancer that has spread outside of the pancreas or metastatic. 

And as you've heard, the researchers are committed not only to the treatment of the disease and symptom management, but investigating how to best maintain quality of life and further looking into early detection of pancreas cancer or genomic sequencing and gaining insight into the cancers microenvironment and the unique features of the individual patient cancer and how it changes along the treatment continuum. 

Some of these trials do not involve therapeutic or treatment of the cancer, but involve what's called biospecimen trials and [if there], then I think of patients as heroes because they're contributing to the body of knowledge that may affect them directly or the patients at large. 

So, our actively enrolling therapeutic trials currently are over 15 clinical trial this is amazing.  And more trials are opening up every month.  The combinations of immunotherapy and chemotherapy immune modulators that change the metabolisms of the cancers and pathways in which they spread and grow, really changing the platform that the cancer works off of. 

These are done in combination with chemotherapy.  There are absolutely no placebos used in treatment of pancreas cancer patients. 

Targeted therapies that basically are attracted and work on specific molecules on or in the cancer cell as well as identify targeting mutations such KRAS or a BRCA mutation.  These treatments are selective to the cancer cells only and are not benign in their side effects but they do not affect the entire systemic held such as chemotherapy does. 

Very, very exciting and I know you'll hear more about this today, is vaccine trials.  There's unique vaccine trial that Dr. Balachandran is the principal investigator on and it's an interdepartmental trial with surgery as well as medical oncology.  It's unique.  It basically is a personalized vaccine that's developed from the patient's old tumor. 

So, these are very exciting development they build of established therapies and introduce novel agents or new agents that are not FDA approved.  So, the decision, as to which trial or even if a trial is an option for an individual patient is based on many factors.  It's part of the well-developed care plan between the patient, family, and physician.  And considerations in the planning will be the stage of the disease, the patient's overall well-being and state of wellness and symptoms. 

Past treatment history.  If any characteristics and unique features of their own cancer and their and the presence and absence of mutation.  Most importantly, the patient's desire and ability to participate in a clinical trial, participating in clinical trials requires extra effort, the possibility of known and unknown side effects.  And so, fully informed and conscious of the decision-making processes is essential. 

And knowing that a clinical trial is not identified as better than the FDA-approved treatment, it offers additional novel cutting-edge science that for the individual who wishes to participate and who is eligible to participate wants to. 

So, I guess in summation, regardless of any patient or individual background, nothing in your life prepares you for this type of decision, participating in a trial or not.  It's a thoughtful decision and our physicians and research team here want to listen to understand who you are as an individual, what your goals are, to expertly inform and guide and support you and your family along the decision process and along your journey.  Thank you. 

Jeffrey Drebin:  Thank you, Robin.  You had mentioned the exciting efforts in immunotherapy, immunotherapy has really been a game changer for other types of cancer, melanoma, lung cancer would be prominent examples. 

Eileen, can you talk about immunotherapy and where we're at in pancreas cancer?  That seems a higher bar right now. 

Eileen O'Reilly:  Yes, indeed.  But I do think there's a lot happening and I think we are going to solve this issue of making pancreas cancer an immune responsive malignancy with all the really exciting science that's going on. 

So, just thinking about this, there's about 1% of people with pancreas cancer who have a context of what we call mismatch repair deficiency or something called [Lynch] syndrome which is part of the reason why their cancer develops in the first place. 

And for that small subset, immunotherapy drugs, the one – that ones they advertised on the television every day are effective and useful and are part of standard practice and are FDA approved for pancreas cancer. 

But that, in truth is the minority of people with this disease.  And so the strategies that are in development are to try to get the immune system activated in pancreas cancer to get the right cells present in the tumor to switch them on and to have the immune system do the work against the cancer cells as opposed to the treatment directly tackling the cancer cells once on a – in [innate] immune system be activated. 

And so, there are lots of ways to do this.  And, Robin, in her very comprehensive review there of clinical trials and what they're about, provided some context for this.  So, one way that is a building block is adding immunotherapy to chemotherapy.  There's a whole series of trials with that type of platform and adding additional agents to that. 

The other strategies are combining immune therapy and the class of drugs which is previously mentioned called PARP inhibitors.  There's in certain genetic context that looks to be a very interesting way to proceed. 

There are a number of vaccines and you heard about one exciting one in the early phase that's been looked at after people have undergone surgery, but there are others targeting and RAS and RAS being a critical gene in the development sustenance of pancreas cancer and it's present in about 90% of people who have this cancer in the tumor.  It's not a gene that one inherits and it's been, again, a high bar to tackle this gene but there are now some strategies looking at vaccinating against KRAS which I think we're going to see a whole series of developments in – in that space over the next couple of years. 

And then there are other approaches that we're learning from our colleagues who look after patients with blood disorders such leukemias and lymphomas and things like CAR T cells which are highly innovative strategies that switch on the immune system and target specific molecules on the surface of cancer cells. 

Again, early in development in pancreas cancer but that and related T cell approaches are a very, very active area of research.  And it's, I would say, it's a key part of our portfolio here at MSK in various settings of pancreas cancer. 

Jeffrey Drebin:  Thank you, Eileen.  It's – our listeners may be interested to know that the vaccine trial that is ongoing for the personalized vaccine trial that Robin referred to which is being led by Dr. Balachandran and by yourself, Dr. O'Reilly, is actually involves a custom vaccine that is an mRNA vaccine made by the company that’s collaborating with Pfizer on the COVID vaccine that people may read about last week. 

So, although the COVID vaccine will hopefully get into widespread use sometime in the coming months, patients at Memorial going back to the early part of this year have been receiving mRNA vaccines against personalized tumor antigens made by the same company.  So, this technology, I think, is something that is clearly advancing on many fronts. 

I'm going to shift gears a little bit because in the subject of clinical trials, Chris, what do we have in radiation therapy trials?  I'm asking Chris Crane.  I'm sorry.  We have two Chrises on the line.  Chris Crane.  What do we have for radiation therapy trial? 

Chris Crane:  Now, the one that I mentioned before, I think the most promising avenue forward in the clinical trial realm is to try and again use the effect of antigen shedding by an ablative radiation dose as – and combine that with immunotherapy.  So, we have a trial that uses immunotherapy with durvalumab during radiation and after ablative radiation. 

This strategy has been successful in lung cancer and improving survival and patients treated with [tentative] radiation that could be due to what we call an abscopal effect or it simply could be an adjuvant effect.  It's unclear. 

But I think that this is – this is something that could have promise in patients with pancreatic cancer.  We have another trial which is for the high-risk adjuvant – I'm sorry, the high-risk surgical patients who may not be going to surgery.  This is simply a trial that where we give ablative radiation. 

If their tumor becomes resectable, they have surgery.  And the purposes of that trial is really more to document the possible adverse event that could occur if you're giving high doses of radiation and patients go to surgery. 

But I think the most promising thing that we do that’s unique is giving the high-dose of radiation for patients who are most likely not going to be going surgery in the first place.  It's not really always on a clinical trial but that’s the novel thing that we do. 

Jeffrey Drebin:  Thank you.  Thank you, Chris.  Well, I think we've all talked about the clinical trials and it's exciting time.  But it's really research that drives these advances. 

And, Christine, as the leader of the Pancreas Cancer Research Center, can you talk briefly maybe about some advances that are being made on the research front that will ultimately lead to advances in diagnosis and treatment circulating tumor DNA, stroma, other things that you wanted to – you might want to come about? 

Christine Iacobuzio-Donahue:  Absolutely.  And it will be a challenge to keep it short because there are so many incredible things going on in the center.  I think one of the main things to mention is that we have created a very large resource of what are called patient derived organoid models and what that entails of taking a piece of the live tissue, for example, if Bill or Jeff do an operation and they remove pancreas.  We would take a sample of that and put it into a culture and be able to keep it alive. 

But in three dimensions, a way that of growing the tumor that’s much more representative of how the tumor is growing in a person.  And with those models, we've been able to do a number of things.  And one of them, that we're exploring in doing a lot with is related to a concept that's really emerged in the past two years about pancreas cancer is that pancreas cancer has two phenotypes or two different ways of growing and presenting of cells. 

So, for example, there's a typical pancreas cancer where the cells grow as little glands and then there is what's called a basal like pancreas cancer where the pancreas cancer cells transform into more of a squamous cell kind of morphologies.  So, squamous cells or cells that line your esophagus, for example. 

And that is the change that’s been recognized for years, but the significance of it is really only now come to light and been appreciated that it is something that pancreatic cancers, for example, the squamous phenotype used to be thought of as a rare variance, so we now [know] not so rare and if you look hard enough for it, many pancreatic cancers undergo this transformation. 

And it's important because that transformation is associated with resistance of therapies that we know work for our patients with pancreatic cancer.  So, we are working very hard to best identify the biomarkers of that type so we can identify which tumors are going to develop this phenotype. 

We are working to find drugs that might the cells, once are squamous, become more sensitive to and we've completed a high throughput screen related to that. 

And basically, we're using these organoid models which represent the full spectrum of pancreatic cancer genetics and genomics to really understand how to do personalized medicine, how to best achieve that, an efficient way for every patient. 

And I'll just say one final thing were doing.  It ties back to what Eileen had mentioned, again, about patients with BRCA2 mutations are more likely to be sensitive to cisplatin or PARP inhibitors. 

When patient have a BRCA 2 mutation and they're sensitive to those therapies, they – actually they have what we call a BRCAness phenotype.  But we actually say many pancreas cancers that have a BRCAness phenotype.  They behave just like they have a BRCA 2 mutation, but there's no mutation in the gene. 

So, there's actually many more patients who might be amenable to those therapies and we are working very hard using the organoid to really try to define what that means.  And again, all towards using this information so when somebody comes to MSK and their diagnosed, we'll be able to look at their tumor and figure out all the genetics and all the mechanisms going on to personalize the optimal therapy for that patient should the standard of care stop working. 

Jeffrey Drebin:  Thank you, Chris.  I hope when we hold these sessions in the coming years, many of those great projects will have moved to the clinic and be helping our patients. 

Christine Iacobuzio-Donahue:  I think they will. 

Jeffrey Drebin:  I'm going to shift gears a little bit to Robin.  We had a listener who asked are there any daily activities that will help to prevent pancreas cancer?  Robin? 

Robin Brenner:  Well, thanks.  I wish I had the magic answer here.  But in summary, there's some preliminary and ongoing research that shows there are several things we all happen or control to reduce the risk of pancreas cancer.  But there's not one thing specifically. 

For a select group of individuals, there is specific preventative actions that may be recommended based on presence of an inherited genetic findings such as a BRCA mutation.  But in general, we can all, if we are, stop smoking, reduce alcohol intake, lose weight if you're obese because obesity is a risk factor for pancreas cancer.  Limit red meat and poultry with skin.  Limit process, smoked, or cured meats such as hotdogs, bacon, beef jerky that are made with nitrates and preservative. 

Go ahead and do your routine cancer screening and physical exams because pancreas cancer is often found unintentionally through routine team exams.  And if you have a family history of pancreas cancer or BRCA mutation, speak with your physician about recommending a screening MRI or other screening test that they might recommend. 

And be alert your symptoms.  Be present and listen to your body.  Symptoms such as bloating, pain, sudden onset of diabetes, especially after the age of 50, weight loss, yellowing at the skin called jaundice are all symptoms to be alert for and to seek medical advice. 

So, identify your risk factors.  Ethnic – ethnicity is something also that may [pair] you with a higher risk such as Afro-American ethnicity, Eastern European background, having Ashkenazi Jewish background are also risk factors.  History of personal chronic pancreatitis, a family history of [tumor], close relatives with pancreas cancer or breast cancer or ovarian cancer or prostate cancer. 

Environmental exposure is always something we think of as what am I exposed to, is this going to cause cancer?  Well, it's not like the diagnosis of mesothelioma which is directly attributable to exposure to asbestos, here we have no direct connection established as yet.  Currently, research is there. 

But we know that pancreas cancer is one of the diagnoses recognized from 9/11 exposure.  So, be aware, be present.  Listen to your body.  And overall, just remain active and enjoy the things you've been doing. 

Jeffrey Drebin:  Thank you, Robin.  Good advice for us all. 

Bill, several of our listeners asked about the different tumor types.  When we talk about pancreas cancer, there are actually several types of cancer that can arise in the pancreas and sometimes that has important implications for treatment or prognosis.  Could you go through those? 

William Jarnagin:  Sure.  So, the tumors of the pancreas, solid – solid masses that arise in the pancreas are more often malignant than not.  And the cancers of the pancreas are generally broken down into two different types, those of the exocrine pancreas or the spells and other structures that they deal with, the manufacturer and transport of digestive enzymes into the intestine or of the endocrine pancreas and those of the cells in the pancreas that make hormones that do various things such as insulin, and glucagon, regulate sugar metabolism, et cetera. 

Tumors of the exocrine pancreas are much more common and they include the typical, what's called ductal adenocarcinoma which is the most common type of cancer that arises in the pancreas. 

And that's – when we say the word – the words pancreas cancer, that's what everyone thinks of.  And this is the most aggressive form of cancer that can arise in the pancreas. 

There are some subtypes of this, however.  There's typically adenocarcinoma of which is a description of how the cells look under the microscope to the pathologist.  There can be cells that have a squamous differentiation and look a little bit different although they tend to behave similarly to the adenocarcinoma types. 

There is also a type of cancer that arises in a condition called IPMN and we'll talk about that a little bit later, I think.  This is a type of a cyst that arises in the pancreas that is benign it starts but then progresses in some people to cancer. 

And this can give rise to a particular type of cancer called colloid carcinoma and this is certainly an invasive cancer.  But it has a better prognosis than the typical ductal adenocarcinoma that I mentioned previously. 

The endocrine tumors are a very interesting group of tumors that – and make these cells or these tumors arise from the different endocrine cells within the pancreas.  And in some patients, they can – they have hormonal activity that that mimics the cells of origin from which they arise. 

So, for example, some people have something called an insulinoma which is a tumor that secretes insulin and high amounts and can cause problems with sugar levels or a gastrinoma which makes of these tumors make a protein that stimulates the stomach to make acid. 

Many of these are – have a fairly benign course, although, certainly others can be more aggressive in spread.  Most of these pancreatic neuroendocrine tumors, however, are what we call nonfunctional.  They don’t make proteins that have any effect on other organs. 

These pancreatic endocrine tumors have a wide spectrum of behaviors.  They range anywhere from something called well-differentiated and low-grade tumors which are often well-behaved tumors over time and can often be cured with surgery to tumors of much higher grades which are more aggressive and more difficult to control. 

The endocrine tumors are typically, I say, have a better prognosis than the exocrine tumor, pancreatic ductal cancer.  But they still are aggressive and they – they do cause problems and they can kill people. 

This is a type of tumor that Steve Jobs had.  The pancreatic ductal adenocarcinoma is a type of cancer that Alex Trebek has.  So, both men, unfortunately, died of their cancers and it just shows to how both can have lethal outcomes. 

But those are, by far, the most common types we see.  There are other less common types such as something called an acinar cell carcinoma which arises from the acinar cells and within the pancreas that make some of these digestive enzymes. 

Also, unusual type, something called the solid pseudopapillary tumor which is a type of tumor we often see in young people mostly in women that is often cured with surgery, but in some people can spread and give rise to metastatic disease.  But those are – those are much less common tumors. 

Jeffrey Drebin:  Thank you, Bill.  And a sort of related question that people asked about.  What – what do we mean when we talk about cancer stages and for – I'll take that one. 

For cancer stages, virtually, all cancers have a staging system which refers to the extent of disease or how advanced the disease when it is, when it's identified in general stage I disease as in pancreas cancer is a very small and localized tumor and stage IV is a tumor that is already metastatic and has spread to other organs. 

In pancreas cancer which is a little different than other tumor types, stages two and three are defined more by their resectability than by other aspects of how they may have spread.  So, stage II is a tumor that can still be removed.  It's bigger than stage I.  It may or may not have spread to lymph nodes but there is nothing that precludes potential surgery and cure. 

Stage III is locally advanced.  This is a tumor that is growing around blood vessels generally in a way that cannot be removed but has not spread beyond that one region of the body.  And those are tumors which are particularly – we're excited about the possibility of ablative radiation along with chemotherapy for those patients, and in some cases, for bringing those patients under control and even downstage and are tumors to being surgically resectable. 

There's a radiation therapy question.  This is a very specific one, Chris, and I'm not sure it's – you'll have to interpret it because I'm not – I don't know the answer to it. 

Somebody asked how long does it take for bone marrow to recover from targeted radiation on pancreas cancer lymph nodes and is there anything to aid in that bone marrow recovery? 

Chris Crane:  Well, the targeted radiation is really focused away from the bone marrows.  The bone marrow is only minimally affected, so you would only need to have maybe 20% of the dose to the bone marrow to affect the bone marrow but it's fired up away that you may only – you know only the affect, a few (inaudible) body, maybe less than 5% of the bone marrow with radiation treatment. 

But you do three circulating immature hepato – hematopoietic elements that can cause maybe a 10% drop in counts.  But that typically will rebound within a month.  So, really, radiation, has a minimal effect on the counts. 

Jeffrey Drebin:  Thank you.  Thank you.  Different question.  And, Robin, I'm going to direct this one.  Do you – someone wrote in and asked what about studies showing cannabis, which is medical marijuana, may help with this disease or with pain and symptom control?  Can you speak to that? 

Robin Brenner:  Yes.  Absolutely.  So, this comes up very frequently and medical marijuana is increasingly popular complement to traditional medications and treatments for symptoms of pain as well as nausea, anxiety, and cancer diagnosis as well as other diseases.  

However, most marijuana-based products at large do not have an FDA approval so we don't know everything that's in them.  And more evidence is definitely needed, clinical research is needed to confirm the safety, the doses, the scheduling, the effectiveness of marijuana-based products. 

Some therapeutic trials for pancreas cancer actually prohibit the use of cannabis products and herbs, so you need to be fully open and discuss your desire to take these products and where you're getting them.  But there are preliminary studies that suggest marijuana may be of help. 

And of note, all the physicians that I worked with are very supportive of prescribed medical marijuana and the key here is to prescribed.  At MSK, we integrate the supportive care team in managing symptoms and that management may include a prescription for medical marijuana. 

Be aware that there are state laws and guidelines and regulations as to dispensing the marijuana.  So, there's a lot more to come on this subject. 

Jeffrey Drebin:  Well, thank you, Robin. 

Eileen, we had – we did have a question about the pancreatic neuroendocrine tumors which Bill sort of mentioned and pointed out that in general, they're better actors but they can still be lethal.  Do we have breakthroughs in treatment for these? 

Eileen O'Reilly:  So, emerging therapies for neuroendocrine cancers.  Well, one of the – the major ones that we all have our eyes on is something called peptides receptor radio nucleotide therapy or PRRT for short.  And this is a form of targeted radiation that was FDA approved, about two years ago now in North America.  And actually, we used to, traditionally, refer patients to Europe for this. 

But basically, it's using radiation which is given into the vein which targets molecules on the surface of the cancer cells and delivers local treatments and now has become integrated as part of a standard treatment for neuroendocrine cancers as long as they express the target for the radiation. 

So, that’s one important strategy.  The other areas that are in active development are targeting the blood supply of neuroendocrine cancers.  So, I think Dr. Jarnagin mentioned that these cancers have a relatively rich blood supply.  They look different on imaging. 

So, that can be exploited from the perspective of shutting off the blood supply by mechanical means by doing a procedure that our colleagues in interventional radiology do, but also by using certain medications that shut off the blood supply under a number of these that have been approved or in the late stages of development or under review by the FDA.  So, that's kind of an exciting area. 

And for some of the neuroendocrine cancers, the ones that are more what we call biologically active, so the cells are turning over at higher rates.  Those tend to be more responsive to serve traditional chemotherapy approaches and their immune therapy combined with chemotherapy is proving to be an active strategy.  So, that’s a very topical area, also, in terms of development. 

So, I think there's a lot happening and a number of trials ,in particular, trying to sort out some of the nuances of how best to deliver PRRT, what's the best component of the drug, how frequent to give it, et cetera.  So, these are very active areas of research right now. 

Jeffrey Drebin:  Thank you.  That’s – that sounds exciting. 

Bill, we had some questions regarding pancreas cysts and we certainly see large numbers of these at Memorial Sloan-Kettering.  Can you talk about the sort of different types of cyst and how we follow these patients? 

William Jarnagin:  Sure.  Yes.  We are seeing more and more people with these and it's not clear whether people are developing cysts more or we're seeing them more because people get – they get scanned more frequently and the scans are just better at finding them. 

But regardless, they are – for many people, they are clinically really not all relevant.  But they are a source of great anxiety. 

Pancreatic cysts can happen because of inflammatory changes in the pancreas after an episode of pancreatitis or they can be congenital types of cysts.  And these, generally, don't have any [fibrocystic] cancer.  The cyst, however, that we are most concerned about are the ones that are precancerous in nature. 

And these include a cyst called IPMN which stands for intraductal papillary mucinous neoplasm and another type called a mucinous cystadenoma.  Both of these types do carry some risk of malignant change. 

For the IPMN type, there's two different varieties.  One is called a main duct IPMN and the other is called the side branch type.  And the main duct type has much greater risk of cancer than the side branch type.  And thankfully, that’s a less common variety. 

And so mostly, what we see are people who have the so-called side branch IPMNs and this cyst do have some malignant potential but the vast majority of them never – never become cancer.  And it depends a lot on size and other imaging features in terms of the ones that we are worried about and intervene on. 

So, for most people, this cyst don’t become an issue but we don't know which ones are which.  And unfortunately, we have to follow everybody overtime and make sure that they – that they're not changing.  If they change, we then sort of recommend in many people during an endoscopic ultrasound to the system further and maybe do a biopsy. 

And in cysts that are developing these worrisome changes, we do go to surgery to remove them because that risk of cancer starts to increase.  The other type of system that concerns us is this mucinous cyst adenoma, a fairly uncommon type of lesion that we often see in women.  In fact, most often see in women. 

This cyst can actually grow to some size in some people and can cause some symptoms.  But we typically, when we know about them and diagnose them, we remove them because of that risk of cancer and try to eliminate it. 

Jeffrey Drebin:  Thank you.  That’s, I think, the complexity of the whole cyst story, really, I think points out how important it to see an expert like Dr. Jarnagin who can help you sort through which – which type of cyst you have and what needs to be done to manage it most safely. 

We're running very short on time but we do have a few more questions.  Christine, just a – maybe a real quick answer, everyone's excited about research.  What would you say is the most promising thing?  If we had to – if you had to sort of hope or bet on what's going to be the breakthrough that we see over the next few years, where do you think that's going to be? 

Christine Iacobuzio-Donahue:  I will put my money on immunotherapy for pancreatic cancer.  That immunotherapy in combination with agents that exploit DNA damage, repair pathways.  I think that's really going to be a game changer for pancreatic cancer. 

Jeffrey Drebin:  Thank you.  As my grandmother used to say, from your lips to God's ears. 

I'm going to ask our last question to Eileen.  We hear from patients and family members asking how they can help move research and treatment forward.  Can you touch on that? 

Eileen O'Reilly:  Yes.  Thanks.  Thanks, Jeff.  Yes.  And this is a very important topic. 

And as we always say to patients and families that they're our strength and they are our partners and kind of raise awareness and advocate for this disease to participation – to participate where appropriate in terms of fundraising and trials and all of that, I think, is enormously important and helpful, 

And as we also discussed that what is today's current standards went to the rigor and assessments of critical trials, right, and trials and the science and the research is the future.  And I think that's so, so important and you we're enormously appreciative of all the support and help that all our patients and the huge community that we have here at MSK and around the country, sort of appreciate for the needs for this disease. 

Jeffrey Drebin:  Well, thank you for that Eileen.  I want to wrap up now.  I want to thanks everyone who submitted questions and apologize to those whose questions we didn't get to. 

Thank you everyone who took the time to join the call and I want to thank our speakers who have participated and shared their expertise.  We hope you found this session informative and helpful and we plan to host more calls like this in the future and we look forward to speaking with you again. 

A replay of this call will be available soon on our website, MSKCC.org.  We are all dedicated to moving your cancer care forward and want to encourage you again, to be in touch with your MSK doctors and care teams, make all your appointments, do your screening, live that healthy lifestyle. 

If you obtain marijuana, get it from a medical dispensary, not on the street corner.  And schedule all of your procedures.  Don't delay your care.  COVID is frightening but cancer is frightening and remains frightening. 

Please be safe and take care of yourself and your loved ones.  Thank you all. 

Operator:  This concludes today's call.  Thank you for joining Memorial Sloan-Kettering's Information Session for Patients and Caregivers.  Have a good evening.