Melanie Cole (Host): Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole. And we have a panel discussion today to offer gastroenterology updates in hereditary colorectal cancer syndromes. Joining me is Dr. Charles Muller, he's an instructor of Medicine in the Division of Gastroenterology and Hepatology at Northwestern Medicine; Dr. Brittany Szymaniak, she's a genetic counselor and an instructor of Urology at Northwestern Medicine; and Dr. Mohammad Ali Abbass, he's an Assistant Professor of Gastrointestinal Surgery at Northwestern Medicine.

I want to thank you all for being with us today in this panel. Dr. Abbass, I'd like to start with you. Can you tell us a little bit, as we get into this, about your areas of clinical and research focus?

Dr Mohammad Ali Abbass: Thanks, Melanie. So my name is Mohammad Abbass. I'm a colorectal surgeon at Northwestern Memorial Hospital. I specialize in caring for patients with colorectal cancer in general, but specifically in high-risk patients who either have a concerning family history or an inherited cancer predisposition syndrome. My research interest focus on standardizing care for those patients, understanding what we call genotype-phenotype correlation, or how does that gene or genetic problem correlate with a clinical disease and really how to standardize genetic counseling and access to genetic counseling for those patients.

Melanie Cole (Host): It's a really important topic that we are discussing here today. So as we get into this, Dr. Szymaniak, how has diagnosis and treatment of colorectal cancers evolved over the years and hereditary cases in particular? What had been the thought previously regarding these types of colorectal cancers and what is different now? How has that role evolved?

Dr Brittany Szymaniak: So historically, we've relied on clinical diagnostic criteria when it comes to identifying these conditions, because we didn't actually know what the causative genes were. But over the years, our technology has significantly advanced. We now only have genes identified for some of the common inherited colon cancer conditions, things like Lynch syndrome, familial adenomatous polyposis condition. There's a number of other genes that we're now identifying as our scientific understanding continues to expand, and we identify more genetic links with inherited colon cancer. So we've really expanded when it comes to identifying and diagnosing these conditions.

When it comes to the treatment, so for other cancers, they've been able to take advantage of personalized medicine and we're now starting to see those advances in the hereditary cancer space. So for example, we can now utilize things like immunotherapy with Lynch syndrome that takes advantage of the specific pathway that's being affected by this gene mutation. We also have considerations for surgical planning, when somebody has a diagnosis of colon cancer in the setting of Lynch syndrome, which certainly Mohammad and Charlie can speak to more, as well as different types of regimens, even things like aspirin regimens, to help reduce the risk for colon cancer. So things have dramatically changed over the years and we have a lot more options for patients.

Melanie Cole (Host): Well, we certainly do. And Dr. Muller, are there any advances that have significantly augmented your diagnostic and therapeutic capabilities for these types of cancers? Any game-changers you'd like to talk about?

Dr Charles Muller: Yeah, absolutely. And I think Brittany sort of started to allude to this, but one of the biggest therapeutic advances that's been made in Lynch syndrome in particular has been the advent and really the explosion of immune therapy for colon cancer, as well as other types of cancer wherein we leverage the body's own immune system to help treat cancers or even attack cancer cells before they actually form into a tumor. So we've known for a while that Lynch syndrome in particular creates tumors that the immune system is able to recognize. So these types of tumors that arise in Lynch syndrome are highly responsive to immune therapy. So, there have been pretty recent advances in being able to use immune therapy, either by itself or in conjunction with conventional chemo, radiation, or surgery, where we can use this less toxic therapy, and then allow us to kind of minimize these more morbid, conventional cancer treatments.

Another really exciting advancement that is coming down the pipeline is this idea of using vaccines for Lynch syndrome, kind of piggybacking on this principle that the immune system is able to clear Lynch syndrome-related cancers at either an early stage or even before they develop. There is a lot of work being done in developing vaccines that can help us to identify these cancer cells at the earliest stages. And that potentially, you know, even though it's not quite ready for prime time yet for Lynch syndrome patients or colon cancer patients in general, this is something that is a very exciting area of research that could totally change the landscape of colon cancer and Lynch syndrome treatment in general in the next upcoming years.

Dr Mohammad Ali Abbass: I would like to add to what Charlie was saying, there's currently a big national trial for the Lynch syndrome vaccine that's happening, where we'll be enrolling some patients with that trial over the next couple of months. So, people can reach out to us if they have any questions.

Melanie Cole (Host): Certainly an exciting time to be in your field. And, Dr. Abbass, we're going to get into more of the genetics with Dr. Szymaniak, but as we see improved coordination of care, and the opportunity to assess each patient from many viewpoints, can you speak about the importance of that multidisciplinary team? I mean, you guys represent three specialties that all work together for these hereditary colorectal cancers. What are you finding are the largest benefits of that multidisciplinary approach for these patients?

Dr Mohammad Ali Abbass: Historically, management of these patients, especially patients with polyposis, for example, like one of those syndromes, it used to be simple where we had simple rules. We just follow them and just decide on the management of the patients. For example, they have an X number of polyps in the rectum. Then, we remove the rectum or we leave the rectum in place. But with time, we started to learn more and with collaboration with genetic counselors ,gastroenterologists are able to have some advanced techniques to add for removing larger polyps, having even a medical geneticist involved in the conversation and help us understand more how the gene works and how it's working in that specific family. We're understanding truly the natural history of disease, not only overall as a disease, but also in each family specifically. So now, we're able to tailor each treatment, not only based on the disease only, but based on that specific family and how that gene is working in that family.

We always try to keep like a couple of goals in our mind when we're working as a big team like this. Our goal is really trying to avoid death from cancer. So we tailor our treatment just to make sure that the patient is not going to develop cancer and die with it. And also to maintain the patient's quality of life and balancing those goals is very important. We can't just aim on preventing cancer and doing big operations and big interventions and toxic medication. We just need to always balance quality of life and preventing death from cancer. And having a team like Brittany and Charlie and a lot of other people helps us reach a better and more decisive treatment plan.

Melanie Cole (Host): What interesting points you made. And as long as we're talking about family, Dr. Szymaniak, what are the personal and family history features of hereditary colorectal cancer? And while you're answering that speak about the importance of other family members being identified and evaluated by physicians. So tell us a little bit about how the program works and how you identify family members who might be at risk or affected.

Dr Brittany Szymaniak: There's a couple different features that we tend to specifically look for in families. So one of the biggest things is going to be younger ages of diagnosis. Typically, with colon cancer, we're thinking under the age of 50, we're looking for multiple generations of related or similar kinds of cancer. So are we seeing histories of other colon cancer, other GI cancers, stomach, small bowel, as well as things like uterine cancer, ovarian cancer? And we're also not just taking into account a colon cancer diagnosis, like Mohammad alluded to, we also are thinking about polyp histories for patients. So do we have somebody who has a significant polyp burden? Do they have a relative with a significant polyp burden? We're looking for individuals who have multiple cancer histories. So do we actually see somebody who has more than one colon primary or has a combination of a colon cancer and one of those other cancers that I mentioned earlier? We look for rare cancers, things like pancreatic cancer, ovarian certainly would fall into that category as well. Less relevant with Lynch syndrome, but we do in any hereditary cancer evaluation, take into account ancestry, specifically Ashkenazi Jewish ancestry, because there's mutations that are more common in that population, but there are certain Lynch syndrome mutations that are seen more frequently in the Ashkenazi Jewish population.

So we're not only looking at the patient's history, but we're looking at this family history. So it's really important when somebody is talking to their doctor that they're mentioning these other histories in the family so that this can be something that can be flagged for a genetics evaluation. Because if we identify something in the family, that's not only going to impact our patient, but it's going to impact other at risk people that we need to now increased screening for, to either prevent a cancer or catch it early when it's more treatable.

Melanie Cole (Host): So you just mentioned that you can then identify those members and they can receive screening and even possibly medical management that could help prevent that morbidity and mortality. Can you just speak briefly about the practical aspects of genetic testing for other providers that are counseling their patients? Because not only is it genetic testing, but there is counseling that goes with it, which includes, as you mentioned, the history and evaluation, but also emotional status, preferences, all of those things. Can you just speak a little bit about your program?

Dr Brittany Szymaniak: So for any patient that is coming in for an evaluation, certainly we're talking with the patient about what the impact and significance of this testing is going to be. Because like I've said before, this isn't just about the patient, this is about the family. And sometimes, we have patients that are really motivated to try and figure out why there's all this cancer history in the family so that they can then maybe prevent that from happening in future generations if we can start doing increased screening for them. Sometimes we can have a patient that's maybe in the middle of a diagnosis that it becomes more of a conversation of, you know, when might be the right time for them to think about testing? Is this something that they want to put on their plate now? Is this maybe something that we evaluate a little bit later after they've had some time to kind of deal with their diagnosis and treatment? And we always talk to the patient about whether or not this is information that they want to know, because ultimately this is still something that's voluntary and is something that the patient can decide whether or not they want to know. But of course, we're talking to the patient about the benefits of testing and why it can be so important to be able to identify these conditions in families.

Melanie Cole (Host): You made great points and that's such an important part of this whole picture. Dr. Muller, what advancements have been made in tailored medical and surgical management of Lynch syndrome? What makes Northwestern Medicine so uniquely qualified to treat these cases?

Dr Charles Muller: That's a great question, Melanie. So, we've learned a lot about Lynch syndrome over the past several years and have had a pretty significant paradigm shift in how it's been treated. So historically, especially when we didn't have widespread genetic testing, when we identified individuals with Lynch syndrome, it was kind of a cookie cutter diagnosis in terms of how we would screen people and how we would manage people if they developed a cancer. Over the past several years though, as genetic testing has sort of exploded and we have been able to make use of pretty large prospective registries across multiple institutions, constituting thousands of patients with Lynch syndrome, we're able to define better what the cancer spectrum and risks are with each of the individual Lynch syndrome genes, and then potentially even what an individual mutation within a gene might imply for a patient's cancer risk.

So nowadays, we're able to look at an individual's particular mutation and be able to make more tailored recommendations about how they should be screened because some people have considerably lower colon cancer risk, for example, than individuals with the most highly penetrant genes that we've identified. We also take into account family history for an individual. When we look at someone with a particular mutation, it's important to factor in what sort of cancers have run in the family, even if we think a gene might be particularly low risk for a certain type of cancer. If we see that a certain cancer is running pretty frequently in a family, then that's going to be a red flag for us and will kind of make us want to do more intensive surveillance.

One of the advantages of Northwestern is really our multidisciplinary group of people who have a lot of expertise in this. So we have people who are at the top of their game and know the latest research about genetics, but also have a lot of experience with more the art of hereditary colon cancer treatment and how to factor in family histories and patient values in terms of how we do treatment. So we have a weekly discussion about our hereditary cancer and Lynch syndrome in particular patients that includes people from multiple specialties, all the stakeholders who would be involved in a patient screening, and we can kind of put a patient's case together and look at the whole picture holistically to come up with a tailored plan.

So, this is something that Northwestern is uniquely situated to do. The other advantage that we have is that we, in our hereditary cancer clinics, are compiling a registry of Lynch syndrome patients. So as we see these patients come through our clinics, we're able to compile clinical data to learn more about them. And, not only that, if we have therapies available, we have a pipeline ready for accessing new and innovative therapies for Lynch syndrome patients, so it's a really exciting time to be treating Lynch syndrome at Northwestern.

Melanie Cole (Host): Well, it certainly is. And Dr. Abbass, can you describe what's been learned about optimal management and surveillance of adenomatous polyposis syndromes. What makes Northwestern Medicine uniquely qualified to treat these cases?

Dr Mohammad Ali Abbass: We approach those cases as a team. So for example, a patient that has FAP or polyposis, me and Charlie will take care of them together from the beginning. So usually, the age of presentation is late teens if the family is new to us. If we've known the family before, we'll start seeing those, children around age 11 or 12. We'll start doing their colonoscopies around age 12, because we want to monitor the number of polyps they have and how is that changing over. And based on that number of polyps, we'll usually have a conversation between me and Charlie and sometimes with the genetic counselors based on the specific gene mutation and the location of it. And then we'll decide based on how things are changing over time when is the best time to operate on that patient. And if there are other things we can do before operating on them. We also keep in mind focusing on the psychosocial aspect of the patient, because we want to allow them to just grow and avoid getting a big operation throughout their early teen years. So we try to make sure we monitor them closely until after high school and then offer them an operation after that.

The advancement that have happened, like I mentioned before, is we don't just follow rules and means of like specific numbers, specific time do this intervention. We look at the patient as a whole, like Charlie mentioned, and we approach it holistically. So how is the patient feeling? How's their psychological status? How is their polyp burden changing over time? What is their gene mutation and what is their family history? And then, we decide on a plan to approach them.

Charlie also mentioned the registry that we have. We enroll patients that have polyposis or Lynch syndrome in that registry and the purpose of it, for us to keep tabs on when are the patients due for their next set of surveillance. And we make sure that we alert those patients so they won't miss their surveillance. Also, we use that registry to look at our data and see if we're learning something over time or do we need to change how we're doing things too?

Melanie Cole (Host): This is a great topic. What an interesting and informative podcast this has been. Dr. Muller, what else is important for physicians to keep in mind when treating patients with hereditary colorectal cancers?

Dr Charles Muller: I think that the most important thing for physicians to keep in mind is that individuals with a hereditary colon cancer diagnosis, that this is often a scary time for them where they're facing prospective surgery or chemotherapy or radiation. And a lot of times, there's a tunnel vision for patients about their cancer treatments. So the considerations of their at-risk family members or of their additional cancer risks that might be associated with their hereditary colon cancer, sort of take a backseat to that. So I think that's where our job comes in as physicians who take care of people with hereditary cancer, we have to consider these things for them.

And as Mohammad mentioned, we try to factor this in with the psychosocial aspects and try to gauge when patients are ready to handle these bigger issues that might be an issue more down the line while they're focusing on the immediate cancer treatment. So, it's one of the most rewarding aspects of taking care of people with hereditary cancer, is that this is really a family problem, but it's also a family solution. So we get to see patients across multiple generations. And often this is success story when you're able to engage multiple family members, identify people before they get cancer and then implement these screening strategies so that we can prevent them from getting cancer down the line.

Melanie Cole (Host): And Dr. Szymaniak, last word to you. I'd like you to summarize this all for us as a genetic counselor and bring it all home. What do you feel were the most important takeaways of this multidisciplinary approach to hereditary colorectal cancers?

Dr Brittany Szymaniak: So really, some of the things that we want physicians to keep in mind about this topic is our understanding of the genetics has greatly expanded. So there's a lot more testing that we can be doing for patients now than we were able to do 10 years ago. And making sure that they're talking to their patients about family history so that if there is concerning histories, can we then identify something in the family by doing testing and taking into consideration all of the other aspects that come with these inherited cancer conditions, like we've been talking about. Things like treatment, things like surgery planning, things like vaccines that could be coming down the road and trying to figure out what's going to be the best timing for the patient, what's going to be the best care that we can give these patients and their families. So how can we incorporate all of this information into practice so that we're doing the best for our patients and our families.

Dr Mohammad Ali Abbass: We always tell patients also if they live far away or they have a family member that lives far away, they they can feel free to have their physicians reach out because making decisions is easier for us because we're a big group and we see those patients more often. But if they have a family member that lives far away and they're being taken care of at a different institution, we say just reach out to us and we're happy to help the physicians make a decision that's appropriate for that family member.

Melanie Cole (Host): That's a great point, Dr. Abbass. Thank you all so much for joining us today. Such an interesting topic. And to refer your patient or for more information, please visit our website at breakthroughsforphysicians.nm.org/gastro to get connected with one of our providers. That concludes this episode of Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole.