Selected Podcast

Pancreatic Cancer

In this panel discussion, J. Bart Rose, III, MD, Ravikumar Paluri, MD, and Rogeemon Jacob, MD, discuss Pancreatic Cancer, current and evolving therapies and new ways to approach Pancreatic Ductal Adenocarcinoma.
Pancreatic Cancer
Featured Speaker:
Ravikumar Paluri, MD | Rojymon Jacob, MD | J. Bart Rose, III, MD
Dr. Ravikumar Paluri, MD is an oncologist in Birmingham, Alabama. He is affiliated with University of Alabama Hospital.

Learn more about Ravikumar Paluri, MD 

Rojymon Jacob, MD is an Assistant Professor, Radiation Oncology, University of Alabama School of Medicine.

Learn more about Rojymon Jacob, MD 

Dr. J. Bart Rose joined the faculty of the UAB Department of Surgery Division of Surgical Oncology in 2017 as an Assistant Professor. He has a combined research and clinical appointment. He has been engaged in scientific research for fifteen years. His current research focus is on mechanisms driving pancreatic and GI neuroendocrine tumor development; as well as investigating new ways to treat this disease.

Learn more about  J. Bart Rose, III, MD 


Release Date:      November 1, 2018

Expiration Date:  November 1, 2021

Disclosure Information:

Dr. Jacob has the following financial relationships with commercial interests:

Payment for Development of Educational Presentations - Varian SBRT Course
Payment for Lectures, including service on Speakers Bureaus - Medtronics, Varian

Dr. Paluri has the following financial relationships with commercial interests:

Consulting Fee - Ipsen, Amgen
Payment for Lectures, including service on Speakers Bureaus - Alabama Cancer Congress

Dr. Rose has the following financial relationships with commercial interests:

Grants/Research support/Grants pending - Central surgical foundation, Reed Foundation

Drs. Jacob, Paluri and Rose does not intend to discuss the off-label use of a product. No other speakers, planners or content reviewers have any relevant financial relationships to disclose.

There is no commercial support for this activity.
Transcription:

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Melanie Cole (Host): Welcome. Our topic today is New Ways to Approach Pancreatic Cancer. And my guests in this panel discussion today are Dr. Bart Rose, he’s a hepatobiliary and pancreatic surgeon in surgical oncology, Dr. Ravikumar Paluri, he’s a hematologist and medical oncologist and Dr. Rojymon Jacob, He’s a radiation oncologist and they are all at UAB Medicine. Dr. Rose, I would like to start with you. Explain a little bit about pancreatic cancer and the prevalence of this type of cancer today.

J. Bart Rose, III, MD (Guest): Sure, I think when we talk about pancreatic cancer, we are mostly talking about adenocarcinoma of the pancreas as opposed to neuroendocrine tumors. Adenocarcinoma of the pancreas is the fourth leading cause of cancer related deaths in the United States. There’s going to be about 55,000 new cases this year and unfortunately, about 44,000 of those people will die including 750 deaths here in the state of Alabama.

Melanie: Wow. That’s quite a prevalence and statistic, so Dr. Paluri, tell us a little bit about the etiology of pancreatic ductal adenocarcinoma.

Ravikumar Paluri, MD (Guest): So, the risk factors, the causative facts for this pancreatic cancer are broadly categories to whether they are inherited, or they are not inherited. Sometimes you call them environmental risk factors. So, this pancreatic cancer or pancreatic adenocarcinoma aggregates in a few families approximately 10% is what we say the patients who are diagnosed with this cancer have a positive family history. And a few studies did identify a few susceptibility genes such as BRCA ATM and another inherited characteristic that we’re talking about is ABO blood type because bigger studies like nurse health study and health professional follow up studies and they compared the patients with blood group O and other blood group types and what they found was there seems to be a little bit higher risk of incidence of pancreatic cancer in the patients with non O blood group and these findings actually they were even validated in a genome wide association study later. And of course, there needs to be additional studies in a prospective manner to confirm these findings. And the patients with cystic fibrosis, they do have increase risk for the pancreatic cancer and chronic pancreatitis is also a risk factor as well. And so, there are a few other epidemiological studies. They pointed out the association between diabetes and pancreatic cancer and coming to the environmental risk factors and the smoking, alcohol and the diet, like high calorie intake; they were considered to be a risk factors for these malignancies.

Melanie: Dr. Jacob what are some of the hallmarks and the clinical presentation of pancreatic cancer? What are some of the first signs and symptoms?

Rojymon Jacob, MD (Guest): Well Melanie the commonest symptom related to pancreatic cancer is the development of jaundice. Jaundice is as you all know, is the yellowing of the eyes and skin and this can happen due to the obstruction of bile ducts due to an enlarging pancreatic tumor. Because of the obstruction to the bile ducts; there could be impaired biliary flow into the bowel which can result in light colored stools or greasy stools. This can also happen due to insufficient pancreatic enzymes which are produced within the pancreas. So, the ability to digest food may be impaired. This can lead to weight loss or poor appetite, fatigue. Some patients have nausea and vomiting because once again because of blocked bile duct or because the tumor pressing in the door to them. And finally, pain or bellyache is also a common symptom that patients present with because pancreas has a really rich nexus of nerves, so pain can be sometimes really excruciating and typically in the upper abdomen. Rare symptoms such as blood clots or gallbladder enlargement, liver enlargement can happen. And also, there is a percentage of patients who present with diabetes. Diabetes as you know is due to abnormally high blood sugar levels which or are due to reduced production of insulin within the pancreas and the reduction in pancreatic insulin of course because of the cancer cells diminishing the active area of insulin making cells. So, these are the common symptoms with which patients present.

Melanie: Dr. Rose it would seem that one of the most important aspects and before we get into some of the newer treatments; is early diagnosis and tell us how important that is to improve outcome prediction and what are some valuable tools that you are using to aid in this early diagnosis? I mean Dr. Jacob has just mentioned jaundice and such but speak about what else you are using and how important this is.

Dr. Rose: Well like most cancers, the outcomes are closely tied to how advanced the cancer is when we find it. So, very early stage pancreas cancers; those that have not left the pancreas or metastasized or involved the lymph nodes have much more favorable outcomes. We have about a 40% chance of curing people if they don’t have metastatic disease or involved lymph nodes. If they have no metastatic disease but their lymph nodes are involved; that drops down to about 20%, it’s variable to get full treatment. Unfortunately, we don’t have good screening tests for pancreas cancer. Oftentimes we find this because of one of the symptoms that Dr. Jacob mentioned and about 50% of the time, that’s at a point where the tumor is already spread to another organ and about 30% of the time; where it has spread in the region of the pancreas to the point that makes resection difficult. So, this can be a rather difficult disease to diagnose. Some people are looking at ways to diagnose this earlier using certain markers in the blood stream, but we really don’t have any good evidence that that is ready to be implemented in the clinics today.

Melanie: Dr. Paluri how important is disease staging as an essential factor in PDAC therapies? Tell us also what’s going on with genetics and early detection?

Dr. Paluri: Sure Melanie. As Dr. Rose just pointed out, about the prognostic factors and we need the staging workup upfront to identify these high-risk factors because they are the ones that will determine in the future the overall prognosis. So, essentially the goal of the staging workup is to assess the extent of the disease spread to the lymph nodes or to the other organs and also identify those patients who are eligible for the resection with a curative intent. And so, at this time, we are staging with a TNM of AJCC and I think the version currently is 8th edition of 2017. And coming to your next question about the genetics and the early detection as I mentioned earlier about 10% of the patients have a possible heritable genetic component and that can be attributed to the genetic causes. There are essentially two categories in there as well. So, one is a genetic predisposition syndrome. For instance, if the patient has hereditary breast cancer or ovarian cancer and they are at high risk of developing the pancreatic cancer as well. And the other syndrome are inherited pancreatitis, Li-Fraumeni syndrome and there are a few others as well. And the second category is a familial pancreatic cancer, and these are the patients who do not have a genetic predisposition risk, but they are defined as a family with at least two first degree relatives who had pancreatic cancer in them. So, that’s why the time of the history and physical is very important to have a personal family history in detail because if you suspect any of them a genetic counseling - a referral to the genetic counselor would help in identifying the genetic component. So, a few studies were undertaken to identify the strategies to detect early. But they were not successful. Part of the reason is what studies have shown was there is no difference in the overall survival when they screen everybody and also because the screening involves this detection with endoscopic ultrasound. Sometimes these mortalities itself would put the patient at risk for some adverse effects. So, what studies are suggesting is you look at only the very selected subgroup of the patients who are at high risk because of this genetic issue to have the screening. And otherwise, there is no formal screening strategies at this time for the pancreatic cancer for the general population just like we do colonoscopies for the colon cancer.

Dr. Rose: And I would like to add to Dr. Paluri’s comments that there are – there is some work being done mostly in single institution centers looking at genetic components that may predict response to treatment. There is some very early data suggesting in a single institution trial that by using a six gene panel that we may be able to predict better who is going to respond to which type of chemotherapy and that could be very useful in the future but as we mentioned before; it’s not quite ready for prime time.

Melanie: Dr. Rose sticking with you for just a minute. Speak about some of the current issues in medical or surgical management and how important when you are diagnosing and staging this is patient selection and if it’s metastasized then that changes what you would decide to do? Yes?

Dr. Rose: It’s extremely important. I think that as a surgeon, I can heave an impact on this disease if it’s a local disease, but unfortunately, the aggressiveness of pancreatic cancer and the lack of the effectiveness of our systemic treatments currently limits a little bit what we can do with metastatic disease. For disease that is still contained to the pancreas or the region of the pancreas and hasn’t spread to distant organs; then patient selection becomes key. These operations to remove these tumors are very complex. They carry with them significant morbidity, both in the short and long-term with impacts in quality of life. So, if somebody – you really have to have a good discussion with these patients and make sure that they are in optimal fitness before embarking on a surgical resection.

Melanie: Such an important point. So, now let’s talk about some of the new ways to approach it including some of the combination or targeted or adjuvant therapies, Dr. Paluri we will start with you.

Dr. Paluri: Starting with the adjuvant treatments, so a few years ago it started with a single drug to be given in postoperative setting and recent ASCO update showed that giving three drugs, three cytotoxic drugs FOLFIRINOX have significantly improved overall survival compared to the single agent. And in addition, the targeted therapies are making their way into some subpopulation of the patients whose tumors have certain mutations. And immunotherapy alone did not show that much of a promising outcome, but they do have a role in very highly selected subgroup and now there have been a few studies that are ongoing with the combination of targeted and immunotherapies. And also, the combination of radiation and chemotherapies and it also seemed to be a very effective strategy. We do have protocol here at UAB and then another important – I want to bring to attention is sequence of the treatment. So, there have been a significant change just recently, the way we treat this cancer. It used to be you start with a surgery if the cancer seems to be resectable, then proceed with adjuvant chemotherapy. But what they found was there has been a lot of recurrence rate in spite of the surgery upfront followed by adjuvant. So, now the needle is moving towards total neoadjuvant where you start with a neoadjuvant chemotherapy that means you do chemotherapy upfront and then you do the surgery and followed by chemotherapy or the radiation depending upon whatever the outcome it is from the pathology.

Dr. Rose: Well I would just say I would like to echo what Dr. Paluri mentioned in that after an operation that’s extremely difficult for these patients to get all their intended therapy and only about 75% of these patients traditionally began adjuvant treatment or chemotherapy after their operation with only maybe at best half of them completing all of their intended chemotherapy. So, it was very difficult for these patients even to get a single agent after a large pancreatic operation which is one of the reasons why we have been switching to giving it to them prior to the operation to ensure that they get adequate systemic treatment.

Melanie: And as this is – this kind of panel discussion is so multidisciplinary and fascinating that I’m able to have all three of you on to speak about the succession of treatment. Let’s look a little bit on the horizon and in the future of pancreatic cancer. So, Dr. Rose I’d like to start with you. Some promising new therapies in the surgical area and even you have talked about patient selection, so, you tell us what you are seeing happen on the horizon and what you are doing at UAB that will be of interest to other providers.

Dr. Rose: I think that the operation itself has not changed much in the last half a century but what we have gotten much better at is getting patients with more advanced disease to the operating room, having them recover more quickly and getting on to intended treatment at higher rates than they used to be. So, I think now that we have some better systemic treatments, we have switched to giving treatment upfront with chemotherapy and now potentially adding radiation as a component to that; we are operating on people that before, had very advanced disease locally that involved not only mesenteric veins but also arteries where their resection of the tumor along with these major vessels was not associated with an improved outcome but in large institution studies we are starting to see that that may change and that is most likely due to this new combination treatment approach where they are giving most of their treatment upfront.

Melanie: That’s fascinating. Now Dr. Jacob to you, and I’d like you to talk about the horizon picture a little bit too as a radiation oncologist where is your role in this now and is it coming in even before surgical intervention?

Dr. Jacob: Okay Melanie. As was mentioned, pancreatic cancer requires multimodality, multispecialty treatment and as a radiation oncologist, my role is number one to improve the likelihood of Dr. Rose being able to remove the tumor by surgery. And I can facilitate this by shrinking the tumor and if for whatever reason, the tumor continues to be inoperable; even after chemotherapy and radiation; then the radiation should be able to reduce the likelihood of regrowth and also to prevent local symptoms. And by local symptoms I specifically mean pain, which is a very common local symptom and obstruction. So, that being the role of radiation; in the coming years, I hope that we will see more precise delivery of radiation to the target. Already radiation is delivered in a very highly accurate fashion. Accuracies in the order of millimeters. We would see the accuracy improve even further so that there is very little spill of radiation to the surrounding local normal structures where we don’t want the radiation to go. And as you know, side effects happen when radiation spills to the surrounding structures. So, we will see techniques being developed which will limit the dose spilled to normal structures. There will be increasing use of stereotactic radiation which is highly focused radiation delivered over five or six treatments instead of the classic 25-30 treatments. We are likely to see increasing use of radiation prior to surgery even though there is no evidence right now there are a number of institutions which are looking into the role of treating patients prior to surgery in all patients. It is likely that they would be – there could be a benefit and finally, we will be making use of techniques such as proton therapy which fortunately UAB is securing a proton machine which will be operational in 2020. We will be making use of the proton machine to more precisely direct our radiation to the targets. So, these are some of the advances that I see in the immediate future in pancreatic cancer care from the radiation oncology perspective.

Melanie: And Dr. Paluri from your perspective as a hematologist medical oncologist, tell us your horizon picture and how this multidisciplinary and multimodal approach to pancreatic cancer really involves all of you and what you see happening.

Dr. Paluri: So, from the medical oncology standpoint, I want to mention that there have been a few challenges in terms of developing the systemic treatment, the chemotherapy. If you look into the last five years, there were not many approvals for the pancreatic cancer. This all boils down to the inherent complex biology of this cancer. So, at this point, the need to manage this cancer in a multidisciplinary manner and the best way to handle any treatment for the pancreatic cancer patients as suggested by the NCCN guidelines or any of the national guidelines is to treat the patient on the clinical trials. So, if you look into the clinical trials right now we now there are several trials with the combination of targeted treatments and also immunotherapies looking into the fine spot where how to get to the right point where we can treat these cancers in a better manner. So, at UAB, and we do have a clinical trial and one of the trials is again the multidisciplinary interventions just like what we all talked about looking at the sequence, that means we give chemo or radiation upfront and looking at the strategy so we have a locally advanced cancer trial where we treat the patients with chemotherapy followed by stereotactic body radiation and if it become resectable, then they will be going for the surgery. So this is how – so we all three disciplines will interact to manage this cancer.

Melanie: Fascinating. Dr. Rose last word to you. Tell other physicians what you would like them to know about pancreatic cancer and when you feel it’s really important to refer to UAB Medicine.

Dr. Rose: Yeah, I think that the important message here is that pancreatic cancer can be treatable. It’s important to have especially patients who have no evidence of metastatic disease should be seen by a surgeon and even those patients who do have metastatic disease really should consider being seen by somebody to discuss clinical trials which Dr. Paluri mentioned that we have a number here. But there was a study that was done over a decade ago now that found that even patients with the earliest stage of cancer were only getting referred to surgery about 40% of the time. And I think it’s very important to have patients be evaluated in a multidisciplinary fashion at all stages of the disease before they decide to go on to palliative treatment.

Lastly, I’d like to mention that in order for us to provide a truly multidisciplinary care experience at UAB, we have launched a pancreatic biliary disease center that brings all the people that have been on this Med Cast along with other providers in surgical oncology, medical, radiation oncology, pathology, transplant, critical care, genetics together including advanced GI and IR and really treat these patients in a true multidisciplinary fashion. Patients can be referred directly to our center and can contact us either through our website or at 1-833-UAB-4PDC, pancreatobiliary disease center. We look forward to helping in any way that we can and working with all providers within the community and all aspects of care for these complex patients.

Melanie: Thank you gentlemen so much for joining us today and for sharing your expertise and explaining the sequencing and what you see on the horizon for pancreatic cancer. Thank you again for coming on the show. A community physician can refer a patient to UAB Medicine by calling the MIST line at 1-800-UAB-MIST. That’s 1-800-822-6478. You’re listening to UAB Med Cast. For more information on resources available at UAB Medicine you can go to www.uabmedicine.org/physician, that’s www.uabmedicine.org/physician. This is Melanie Cole. Thanks so much for listening.