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Welcome to UAB MedCast, a continuing education podcast for medical professionals, providing knowledge that is moving medicine forward. Here's Melanie Cole.

Melanie Cole (Host): Welcome to UAB MedCast. I'm Melanie Cole. And today in this thought leader conversation physician round table, we're examining new ways to approach pancreatic cancer. Joining me is Dr. J. Bart Rose, he's a hepatobiliary and pancreatic surgeon in surgical oncology. He's also an assistant professor. Dr. Rojymon Jacob, he's a radiation oncologist and a professor. And Dr. Moh'd Khushman is an Associate Professor of Hematology Oncology. And they're all at UAB Medicine.

Doctors, thank you for joining us today. And Dr. Rose, I'd like to start with you. So can you tell us about pancreatic cancer today? What are we seeing in the trends? What's changed?

Dr J. Bart Rose: Absolutely. Thanks for having us, Melanie. I think the biggest changes that we're most excited about are in the survival around pancreatic cancer. As some of your listeners may know, pancreatic cancer affects about 60,000 patients a year. And unfortunately, about 40,000 of those will end up dying of their disease. And that survival rate at about 9% has been steady for a long time. But in the last two years, we've finally see that hit double digits where we're having 11% of our patients survive. And even though it's a small percentage change, it's very exciting that we're finally moving the needle on this disease that's been so challenging to treat up until this point.

Melanie Cole (Host): That is an exciting update to share, Dr. Rose, and thank you. Now, Dr. Khushman, we did a previous podcast on this topic, so I'd like you to share any exciting updates. Why are we updating this? Any game-changers that you're happy about?

Dr Mohamed Khushman: Yes, there are two important updates that I would like share. The first one is, for patients who have pancreatic cancer that was successfully resected for many years, we did not know the ideal treatment that we give to patients after surgery to prevent the cancer from coming back. We've tried multiple recipes, but the one that really showed the most effective way to prevent the cancer from coming back eventually was identified and it is FOLFIRINOX. So there is a chemotherapy regimen called FOLFIRINOX that has been studied and it showed to be the most effective chemotherapy regimen that we should give to patients who are candidates for, to give the patient the best chance of the cancer not coming back.

The second update that I would like to say is, in the last five years, pretty much every single treatment option that have been approved for patients with pancreatic cancer have been in just a selected group of patients with specific molecular alterations. So moving forward, not all pancreatic cancers are the same. So if any oncologist has a pancreatic cancer patient, that oncologist should put effort to understand and study the molecular alterations of that specific patient, because this could potentially open the door for additional treatment options that are pretty effective, but need to be identified.

Melanie Cole (Host): Thank you so much, Dr. Khushman, for telling us about that. And Dr. Jacob, with the advent of COVID, how have protocols and recommendations changed? What would you like referring physicians to know about the UAB Medicine program for pancreatic cancer?

Dr Rojymon Jacob: Well, Melanie, like the rest of the world, we were impacted by COVID in early 2020. And we had to quickly adapt so that we caused the least risk to our patients and to our staff, while at the same time, not disrupting cancer care. So that's a major challenge. One of the things we did early on was to adopt testing for all of our patients who needed surgery and radiation. So this made sure that the patients who come to the hospital are not infected with COVID. We also took measures to ensure that their risk of exposure to COVID was minimized by cutting down the number of treatments. For example, in radiation, traditionally, we used to do 25 to 30 treatments. Nowadays, we are treating almost all our patients with a 10 to 13 treatment regimen, which is equally effective. Of course, there had to be some adjustments we do on the machine that we had to make in order to facilitate this. And we thought this was a very important thing in terms of risk to our patients for exposure to COVID.

For patients who are undergoing curative treatment, select patients, we started using more of the technique of stereotactic body radiotherapy. This treatment is performed over five treatments and it's found to be very convenient and extremely safe to patients. And in addition, it also frees up time slots on the machine, which is a very valuable resource. So these are all adaptations we made during COVID period. And I'm sure similar adaptations have been made in other specialties too.

Dr J. Bart Rose: And I'd like to add, we have at UAB been long believers in giving chemotherapy upfront before an operation. And I think COVID really solidified that. During some of the big waves that we were seeing, we would try to keep patients on chemotherapy to get them through that wave and then operate them when the hospital wasn't full of COVID.

What we found was that if you got COVID in a post-op setting, your complication rates were significantly higher. So we really tried to limit the admission rates for people who we're immunocompromised and bring them into a hospital that was full of COVID.

Melanie Cole (Host): Dr. Khushman, do you have something to add to this?

Dr Mohamed Khushman: Yes. I would like to add that actually a group of GI oncologists have published a paper about modifying practices in GI oncology in the phase of COVID-19. They put recommendations to minimize patients' risk. I'm not going to go through those recommendations, but really the recommendations were really to make changes in the treatment approach and doses to minimize the time the patients spent in the clinic or in the hospital and avoid giving treatment that could potentially lead to patients' admission or have complications from treatment when those treatments have just minimal benefits.

So just to conclude there are some, recommendations that are proposed by expert GI oncologists to reduce the chances of patient's required visit to hospitals and such during COVID outbreak.

Melanie Cole (Host): Well, thank you for that. So I want to give you each a chance to speak about your specialty in this next question. So any research studies that you're involved in that other providers may not know about? Tell us about your own research and how treatment has evolved over the years. Dr. Rose, why don't you start?

Dr J. Bart Rose: Yeah, I think there's some exciting things that are happening around pancreatic cancer right now. We are a site for the Alliance Trial, which is going to be a very important trial. We're trying to figure out in people who have very early stage pancreatic cancer, whether or not giving chemotherapy before an operation and then again after is going to be a better approach than just removing the tumor and trying to give all of the chemotherapy afterwards. And this is a very important question to answer because there are significant pros and cons to both approach and the data is not out there to help us make an informed decision.

Some other interesting work I think that we're doing here at UAB, there is a very common mutation in pancreatic cancers in a gene called KRAS. And some of our investigators are looking at a new drug that targets this and, at least an early models that are being funded through our cancer center, are showing some really impressive results. So I think that's years away from being prime time, but it's exciting work nonetheless.

Melanie Cole (Host): Dr. Khushman, what would you like to add to this?

Dr Mohamed Khushman: We do have a clinical trial portfolio for pancreatic cancer that we are trying to expand. We have just completed a clinical trial for patients with stage IV pancreatic cancer that really may change the standard of care. The standard of care now for patients getting first-line is FOLFIRINOX. The trial we have just completed will replace one medicine with a bioengineered medicine. So this eventually may change the standard of care.

Also, Dr. Vickers, our dean, have introduced us to another group of institutions, and they also have introduced to us a clinical trial that would incorporate the genetic makeup of pancreatic cancer and assessing the response to the current treatment and possibly using this data to decide subsequent treatment.

Melanie Cole (Host): And Dr. Jacob, as a radiation oncologist, tell us a little bit about your role and any research that you would like to share with other providers.

Dr Rojymon Jacob: As Dr. Rose mentioned early on, pancreatic cancer is a very difficult cancer to treat and especially patients who cannot undergo a surgery have a rather bad outcome, a very poor outcome. There's a lot of research using radiation, which has happened for inoperable or difficult to operate pancreatic cancer. And one such study which came out recently from a multi-institutional group in US was using escalated dose of radiation. Basically, you increase the dose of radiation delivered accurately to these tumors without causing damage to surrounding tissue. And one technique, which is used to deliver these high doses of radiation, is called an adaptive radiation, which essentially means the treatment is re-planned every day depending on the location of the small bowel and other structures, which is a very technologically intense radiation planning process.

We have plans to open a similar trial, which is going to be a multi-institutional study, which is currently on the preparation that really makes use of five fraction radiation, increasing the doses, and use an adaptive protocol so that we can treat these tumors with high intensity without causing damage to surrounding structures. We expect based on all the preliminary data that this study is going to have a very major impact on outcome.

Melanie Cole (Host): What an exciting time in your specialties. And the next question highlights this very well. Dr. Khushman, how are genetic molecular studies being analyzed using a variety of molecular techniques to look for genetic changes as well as to potentially screen for pancreatic cancer in people that have a high risk of the disease? What's the potential for enhancing targeted therapies, immunotherapies, or other novel agents that tackle pancreatic cancer in whole new ways?

Dr Mohamed Khushman: Yeah, that is a terrific question. As I mentioned before, the last five years, we really have witnessed multiple new drugs that have been shown to be effective in patients with pancreatic cancer. But those new drugs are only effective in patients with specific molecular alteration. So it is the responsibility of the medical oncologist or the team taking care of the patient to really look for those alterations.

Those alterations can be checked on their tumor biopsy or the blood. We have data to support that both blood and biopsies are good to detect those mutations. But there are some differences between the blood and the tissues. But the bottom line is every patient with pancreatic cancer really needs to have their molecular alterations checked.

Some of the drugs that have been approved and shown to be effective in the last five years are immunotherapy for patients with MSI-high pancreatic cancer and patients with high tumor mutational burden, TMB, also patients with BRCA1, BRCA2 and PALB2 mutations. Those patients benefit from platinum-based chemotherapy and PARP inhibitor.

There is a molecular alteration called NTRK fusions. Those also have a new target for them. And some of the newest targets that we have are NRG1 fusions, KRAS-G12C mutations and RETs alterations. So really the last five years, like I've said, have witnessed multiple new drugs that have been shown to be effective. And some of them have already been approved by the FDA. So it is important for us to look for those alterations by testing the tissue or the blood.

Melanie Cole (Host): I'd like to give you each a chance for a final thought here. Such a fascinating episode. And Dr. Rose, starting here with you. You represent three specialties. I'd like you to tell us about your combined clinic and why it is relevant and what are you finding are the largest benefits of this multidisciplinary approach, which is so important for these complex patients.

Dr J. Bart Rose: I think these complex cancers require complex treatment. And I think we've realized that no one physician is really going to be able to be keeping up on all the rapid changes that are occurring in the treatment of this disease. And we rely on each other to deliver the highest level of care to our patients. And to do this effectively, we have to practice in multidisciplinary fashion.

So at UAB for example, we get all of our patients in. we have a commitment for them to be seen by everybody within two weeks. Oftentimes on the same day, they'll be seen by both a surgeon, a medical oncologist, and often radiation oncology. They get presented at a multidisciplinary tumor board that we have every week and we get a chance to review their case, not just with the single person who saw them, but with the entire team and that often leads to changes in treatment. People will remember certain opportunities that may be available for this patient. They may be a candidate for a certain clinical trial. And I think that that really allows for a tailored approach for every patient to ensure that they get the most optimal outcome that's possible.

Melanie Cole (Host): Dr.. Jacob, what's next when it comes to this area of study? Any promising new therapies? Give us a blueprint for future research in this exciting time and the new ways to approach pancreatic cancer.

Dr Rojymon Jacob: Melanie, I think the next 10 years, we'll see changes on three major fronts. First of all, in the area of early detection. This is very important because surgery is a very important component of care of these patients and the vast majority of patients present late in the course of disease and they are not able to undergo surgery. So we really need to detect cancer early.

There are a number of newer tests which are coming up. Some of them are going to be based on detection of circulating cancer cell DNA in the blood. This will help to detect cancer early, in a stage in which the surgeons can perform a definitive surgery and cure these patients. So that's a major change which is going to happen.

Secondly, patients are going to have personalized therapies because even within pancreatic cancer, there are a wide spectrum of cancers caused by different types of molecular mutations. As Dr. Khushman mentioned earlier, molecular testing is going to be commonplace. We are going to look for mutations and changes in genetic makeup and they are going to be specifically addressed.

In terms of radiation treatment, I think the major change is going to be identifying patients who are eligible for escalated dose of radiation, especially inoperable tumors where you can increase the dose sufficiently high so that they can ablate these cancers without causing damage of surrounding tissue. And that's a marvel of new technology.

So, early detection, personalized therapy and a safe delivery of focused radiation are three areas where there's going to be a lot of changes in the next few years.

Melanie Cole (Host): Well, I hope you'll all join us again and update us as all of these things change, so that other providers can hear about all of the exciting work that you're doing at UAB Medicine. Dr. Rose, why don't you wrap it up for us? Any meaningful endpoints, referral information, when you feel it's important to refer to the experts at UAB Medicine? The biggest takeaways for other providers.

Dr J. Bart Rose: I think the most important thing to remember is that pancreatic cancer can be curable and that it is oftentimes very treatable, even if it is not curable. We can extend the life of these patients, improve their quality of life. And for people who may have more advanced disease, I think offering them access to clinical trials is very important because, while we may not have the cure today, the next clinical trial could be the promising treatment that we're all hoping for.

So giving patients options and just remembering that this can be a curable disease, and it's important to refer patients to people who have expertise in this disease. I think that we do a very good job here at UAB, and that we're always happy to see these patients and we commit to getting them in and getting them seen in a multidisciplinary fashion rapidly. We can be contacted through the MIST line through our website, and also through a direct phone number.

Melanie Cole (Host): Excellent points, all. Thank you so much for coming on and sharing your incredible expertise in this exciting time in your field for other referring physicians. And a physician can refer a patient to UAB Medicine by calling the MIST line at 1-800-UAB-MIST or by visiting the website at uabmedicine.org/physician. That concludes this episode of UAB MedCast. I'm Melanie Cole. Thank you so much for joining us today.