Dr. Angela Chaudhari (Host): Welcome to Parts and Labor, a round table discussion with our OB-GYN experts here at Northwestern Medicine. My name is Dr. Angela Chaudhari, and I'm a minimally invasive gynecologic surgeon and serve as the Chief of Gynecology and Gynecologic Surgery here at Northwestern Medicine. I will be your host today as we talk with members of our Gyne-Oncology Division here at Northwestern Medicine. We will be discussing the research and clinical trials that they are leading and involved with across the country that will help so many patients across our Chicagoland area to really access cutting-edge science for their cancer care.

Let's first meet our esteemed physician panel today. First, Dr. Daniela Matei is our chief of Reproductive Science in the Department of Obstetrics and Gynecology and Hematology and Oncology. She's also the Diana, Princess of Wales Professor of Cancer Research at Northwestern University Feinberg School of Medicine.

Next, Dr. Dario Roque is an associate professor in the Division of Gyne-Oncology in the Department of OB-GYN. In addition to his clinical and research roles, he serves as the fellowship program director of the Gynecologic-Oncology Fellowship here at Northwestern University's Feinberg School of Medicine.

And over here, we have Dr. Emily Hinchcliff, assistant professor in the Division of Gynecologic-Oncology. She's also a very busy clinician, a very busy researcher and also very busy as the program director of the Northwestern University's Obstetrics and Gynecology Residency Program, which I am so proud to announce recently was ranked as the number one OB-GYN Residency Program in the country, in no small part to Dr. Hinchcliff's leadership.

And finally, our fearless leader in Gynecologic-Oncology, Dr. Emma Barber, the John and Ruth Brewer Professor of Gynecology and Cancer Research, and the division chief of Gynecologic-Oncology, as well as the director for Robotic Surgery here in Northwestern Medicine.

This group we have here today are really so impressive. They are national and international speakers discussing their cutting-edge research. They've won so many awards for their work. They've cared for and helped countless patients battle gynecologic malignancy. And I was just speaking before we started this podcast today about how even though I get to work with these doctors every day in the operating room, they take care of so many of my patients, I actually don't get to hear about the research and work that they're doing in caring for patients, really on the cutting-edge of science here at Northwestern Medicine. So, I am super excited for this podcast today, because I get to really learn what this division is doing, okay?

So, before we even get started, you know, people always think, "Oh, you're an OB-GYN," "Oh, you're a GYN surgeon," "I'm a benign GYN surgeon." I get asked all the time if I do cancer surgery and I do not. But I really want to hear like, for our listeners, obviously, we have a lot of physicians that know what GYN-oncologists are, but we may have some patients. What kind of conditions do gynecologic-oncologists care for? Dr. Barber, will you start us off?

Dr. Emma Barber: Yeah. Thanks so much, Angela, for that introduction. And I think it's a really great question because the practice of GYN-Oncology actually also varies a lot across the country. Like what GYN-Onc looks like at one institution can be different from another. So here at Northwestern Medicine, we practice what we consider to be sort of full scope GYN-Oncology care.

So, we do surgery as well as chemotherapy, systemic therapy, immunotherapy, clinical trials for gynecologic cancers. We also perform a lot of like complex benign surgery, right? So, cases that are really difficult, you know, transplanted organs, high BMI, et cetera. So, we do some surgeries that are not cancer, right? But they're just complicated.

We do take care of our own patients in the hospital. So, we admit our own patients to our own service. We don't use a hospitalist and we take care of our patients from diagnosis through surgery, through chemotherapy, and also, you know, end-of-life hospice care. So, it's really that full scope of care and all of those activities are kind of what we're involved in as GYN-oncologists.

Host: I mean, that is what I think really makes the specialty of Gynecologic-Oncology so unique is that you really follow patients through that entire journey. You're not just the surgeon doing the surgery, but you're really this patient's physician caring for that patient throughout their entire battle and journey with cancer. And I know that obviously some patients require chemotherapies. Dr. Matei, can you comment on how sort of what our role is in that?

Dr. Daniela Matei: So, I'm a rare bird, and I'm the one out in this group. I'm a medical-oncologist, so I don't do surgery, but I work closely with the division. I'm embedded, so to say, in the Division of Gynecologic-Oncology. My specialty is chemotherapy and clinical trials for patients with gynecologic cancer, ovarian cancer, cervical cancer, endometrial cancer. And I also run a laboratory where I study ovarian cancer metastasis and resistance to chemotherapy. And I strive to bring some of the findings from the laboratory to the clinic.

Host: That is really amazing. And I think that really sort of like prompts me to really want to know a little bit more about how research does impact people. I can only imagine that there's trials that are from the very start, from diagnostic tools, surgical tools, chemotherapeutic tools and then sort of long-term, life-improving tools, sort of when it comes to research. So, I'm really excited to kind of hear about what's going on in the world of gynecology in terms of research that's happening now.

Emily Hinchcliff: Yeah. So, I think that GYN-Oncology is actually an incredibly exciting place to be right now. Just within the past five to 10 years, we've had truly groundbreaking, practice-changing clinical trials that have come out nationally, and that Northwestern has been involved in that have changed patient's care for the better, whether this is the addition of PARP inhibitors, which is an oral targeted chemotherapeutic for patients with ovarian cancer, that has dramatically changed survival that's in the upfront maintenance setting. So after someone gets chemo, they then go on this medicine to prevent the cancer from coming back, or the addition of immunotherapy in endometrial cancer, for example, where, again, we've seen dramatic improvements in how patients do with the addition of these novel agents. So, I think that it's a really exciting place to be and there's a lot of hope right now in GYN-Oncology. So, all of us who get to practice in this space are just so excited to do so and so excited to continue to kind of push the field forward.

Host: I love that term hope, because I feel like so many times when patients get this cancer diagnosis, they immediately lose that hope. And I love that the doctors caring for them really are saying there is hope, there's new technology coming out, there's new research that's happening to really care for these patients.

Dr. Matei, you mentioned that you obviously are doing a lot of bench and clinical trials work. I'd love to hear a little bit more about some of the novel work that you're doing, immunotherapies, antibody drug conjugates. Come share with us what that means for our listeners.

Dr. Daniela Matei: I will give you some examples that are kind of specific to Northwestern. Immunotherapy has been studied in ovarian cancer here as well as in other centers with modest results. However, combination therapies might enhance the activity of immunotherapy in ovarian cancer. And, for example, in my laboratory, we have studied for a long time epigenetic modifications in cancer, particularly DNA methylation. And we have hypothesized that ovarian cancer is somewhat less responsive to immunotherapy because some of the tumor antigens expressed on the surface of cancer cells are hidden.

And because of that, we hypothesized that with we could use a therapy that would make possible unmasking these tumor antigens and make immunotherapy work better. So since I came to Northwestern, we designed a clinical trial. We obtained both federal support from the Department of Defense as well as support from our partners’ pharmaceutical sponsors. And we conducted a clinical trial for 40 patients with ovarian cancer using a hypomethylating drug to unmask this tumor antigens and immunotherapy. In this trial, we had a few patients, probably about a third that had either responses or stable disease over a long period of time. And we also tried to push a little bit further and obtain biopsies from these tumors before and after treatment. We analyzed these biopsies in my laboratory in the Lurie Cancer Center to try to find predictors of response to treatment. And what we found was something unexpected that had not been reported at the time, which is that B cells, not T cells, are the ones that kind of predict those patients who are likely to benefit from immunotherapy. Subsequently, other investigators also recognized the significance of B cells to immunotherapy. But at the time when we reported the study a couple of years ago, that was a very novel finding. I know that Emily also runs a clinical trial around immunotherapy in a rare ovarian cancer. Emily?

Emily Hinchcliff: Yeah. So, I think that one of the ways that a novel drug kind of impacts patients and gets to patients is exactly as Dr. Matei just mentioned, from her lab finding novel things, finding drugs that can impact those novel things, and then bringing it to patients and seeing what the impact is.

The other way that I think a clinical trial often kind of comes to be is based on iterative improvement of what we know. And so, I designed a clinical trial based on some of my work in fellowship that came out of the results from an additional other clinical trial that showed that in a rare ovarian cancer, something called ovarian clear cell carcinoma. There was a subset of patients who responded really well to immunotherapy, which is not something that we generally think ovarian cancer responds to. And they had a particular mutation inside their cancer cells that we partnered with a pharmaceutical company that has an inhibitor of that particular cell pathway. And so, we are currently combining immunotherapy, which leverages the patient's own immune system, plus this novel agent to see if we can gain the same level of response in patients who don't have that particular mutation.

So, I think that investigator-initiated trials are something that not every institution has. It's something that's unique to Northwestern. And then, I also think that rare tumor trials, trials for patients who have rarer subtypes of cancer are not common, but can be done really successfully at a place like Northwestern because we are such a hub for patients. Dr. Matei, anything else?

Dr. Daniela Matei: I also wanted to mention that one of the major advances for endometrial cancer treatment is incorporating immunotherapy with chemotherapy upfront. But one thing that perhaps is less well-known is that the first study that looked at chemotherapy with immunotherapy in endometrial cancer was a trial that Dr. Barber and myself put together. And that examined the safety of this combination and the activity. The combination was really active. This was a very successful trial, upfront treatment with chemoimmunotherapy. And that actually led to a national trial that examined this combination against chemotherapy alone and demonstrated the superiority of this regimen. So, this, again, shows you how important research done here at Northwestern Medicine is to advance new combinations on the national stage.

Host: I mean, what I am really impressed with everything that I'm hearing about, guys, is that we are really looking at patients' clinical picture, identifying patients who aren't responding to different treatments and different therapies on the clinical side. Taking that back to the bench, actually looking for the markers to actually identify what might be working for people and then trying to put it all together in the clinical space. And this is like all done, like essentially in this room, like with the people in this room, and big teams, of course. But you know, I think that is what I find so unique. And as Dr. Hinchcliff said, like, really there's not a lot of other places when you think about the places in Chicagoland people can go, that they can get sort of this very cutting-edge research that we're looking at your cancer. We're trying to figure out what best treatments are for you, both based on protocols and based on what your cancer looks like and actually taking this further to really advance Gynecologic-Oncology on a much, much larger scale. Such cool work, guys. I'm really, really so impressed as I always have been with all of you.

I think though, you know, it's interesting, as we may have some patients on the call too, obviously every patient wants to know what treatments are going to impact their cancers the best, right? But also, they need to figure out how to live with this cancer, right? And so, I would love to hear sort of what work you guys are doing in symptom science, in survivorship after diagnosis of these cancers. Dr. Barber, I know you do work in this area, so I'm going to leave this to you.

Dr. Emma Barber: Yeah. So, I think I echo everything you said, right? We are cancer doctors, you know, fighting cancer, right? Improving immunotherapy, trying to get better responses and, you know, essentially make this cancer go away, right? It's a huge priority.

But the other thing we hear from our patients is just all of the toxicity of the treatments, right? The surgery, the months and months of chemotherapy. You know, we talked a little bit about maintenance drugs. That's years of therapy that people are taking, right? And so. We hear from patients kind of about how this is affecting them, and symptom science really tries to work on how do we decrease the toxicities of these treatments so people can live, you know, only longer, but also better. And so, that's what I focus on.

We have a few different studies here at Northwestern that have focused on this a lot, on physical activity. We have two NIH-funded clinical trials. One is called Fit4Surgery, one is called Fit4Treatment. Fit4Surgery basically focuses on ovarian cancer patients. They are undergoing chemotherapy prior to surgery. I often tell my patients, like, this surgery is like running a marathon, right? We got to get you ready, right? So, it's about that physical activity beforehand. And that trial completed, we enrolled 30 patients and we found in a randomized trial. And we found actually that they were able to dramatically increase their steps by over like 40% per day, which I was so impressed with our patients, okay, to do that while you're getting chemo, you know, before surgery. But they were really able to increase their steps and we found that this had beneficial effects on patient-reported outcomes, right? Like how they're feeling, what their fatigue is, what their physical function is. And so, you know, we're taking that and trying to do that in a larger study looking at Fit4Surgery, sort of across institutions in a larger population of patients. Fit4Treatment was trying to open it up to more people, right? So, anybody on cancer treatment who's receiving a systemic therapy, immunotherapy, chemotherapy, whatever, for any gynecologic cancer. And so, it's working on trying to increase physical activity. We see that this is associated in a large New England Journal of Medicine publication this summer with improved survival actually from cancer, in colon cancer. So, it's pretty cool. We're trying to bring that to GYN cancer.

The last thing I'll mention is another thing we heard a lot from our patients is this chemo brain concept. So, we have an active trial that just closed of 60 patients looking at a cognitive intervention, right? How do we improve sort of brain functioning using sort of some computer games, essentially tools, you know, that are obviously validated and studied to try to improve cognitive function. So, we're excited to present those results. We're writing them all up now, you know, for the meeting, coming up, but again with symptom signs, just trying to see how do we attack these things that patients are telling us about? Fatigue, nausea, neuropathy, chemo brain. You know, how can we improve all these things so that our patients live better?

Host: I mean, I just think, as I'm listening to you, I think, you know, it's absolutely the opposite of what often people think. They think they get this cancer diagnosis, they are going to have chemo, and they're going to like be stuck in bed. And then, how am I going to be like up and ready for surgery? And I think it's amazing that we're actually starting to really get people on their feet, really get them sort of really prepped and ready for surgery. And I think, for patients out there listening, I think this is such an important thing to hear and understand. Of course, you're going to need your rest during those times as you're going through treatments, but you also can be out there and being active and really keeping your body healthy, during all this work. So really, really amazing research, you guys.

Again, I am really overwhelmed by the work that you do for our cancer patients. And just to reiterate for our listeners, you know, Gyne-Oncology really covers cervical cancer, ovarian cancer, uterine cancers, like we do all the cancers of the pelvis, peritoneal cancers. And so, like, these sorts of research studies that we're doing are really impacting people with all those different cancer types. You know, when we think about research though, there's a lot in the media, and I know our physicians listening certainly hear about this, that really the studies are designed for like one type of person, one, you know, certain type of age, certain type of health, certain type of race. And really, when we think about all these studies we're doing, you know, are they really applicable to people across the spectrum of people getting these cancers. Dr. Burke, I know you work a lot with diverse populations and cancer care. I'd love to hear your thoughts about this.

Dr. Dario Roque: Yeah. So, one of the first things that I like to tell patients is when they come to see me, they have to ask me, "Do you have a clinical trial available for me?" Because I believe that should be the standard of care across the board, especially in patients that have recurrent cancer.

And just like we've been talking about, there's definitely been a lot of advancements in GYN cancer as a result of those clinical trials. The issue that I have seen, and not only me, many people have noticed is the number of diverse patient populations that are actually enrolled in those trials is very small, which is not surprising, because, you know, a lot of times those trials are open in places like Northwestern, which is in downtown Chicago, a very large academic medical center. And we are very, very lucky to have all of those trials accessible for us here and for our patients. But the moment you start to move away from the downtown area, so the moment you go to the south side, the west side, you start to get into rural Illinois, then there's still patients with gynecologic cancers in those areas that; A, either don't have the access to these clinical trials or they don't trust clinical trials because, I believe, a lot of times people say, "I don't want to be a guinea pig."

So, part of my work is to go out into this community. So, I do a lot of work with community-based organizations, and I'll give a couple shout outs to Sisters Working It Out, ALAS, these are community-based organizations that work with cancer patients by supporting them. And I go out and they have a lot of seminars talking about clinical trials, just cancer in general and supporting their patients. And part of my job is to help them understand this is why clinical trials is so important. And I also want to give a shout out to the Bears Care Organization because they are the philanthropic arm of the Chicago Bears. And they have supported some of my work in terms of being able to go out in the community and helping promote the importance of clinical trials. Because I think we need to increase the diversity of clinical trials. And the work that the Bears Care have supported have allowed me to develop this website. It's called Impact Chicago. And the goal is to collate all of the clinical trials available throughout Chicago, not just at Northwestern or other institutions, just to make it easier for some of those community-based organizations to help their patients find clinical trials that are applicable to them and help direct them to the correct institution. Because a lot of what we do is collaborate with other institutions as well, because many times we may have trials that are not open somewhere else, and those institutions can refer patients to us and vice versa. We collaborate a lot with physicians and other institutions so that we can refer patients to them if they have an applicable trial.

Host: You know, can you just speak to this term of like being a guinea pig in a trial, right? I think a lot of patients feel that way, like, "I just want to do what's there because that is what's been proven and that can really help me." How do you talk to patients about why these clinical trials are so important, why they should participate, and really how that impacts them both personally and in the larger scale?

Dr. Dario Roque: So, one of the first things that I tell patients, in cancer clinical trials, you're always going to get treatment. You're either going to get the standard treatment or the standard treatment plus a newer drug. Sometimes for trials that are earlier phase, meaning that are first-in-human studies, in those cases you're still getting a treatment that may or that may not have been approved already. But those are situations where really there's not a lot of other options left. So, the amount of benefit that you can derive from that trial is significantly higher than you're not receiving any treatment at all.

So, one of the biggest myth that I try to dispel with patients is the idea that you're going to be getting some sort of placebo or sugar pill. In cancer clinical trials, you're always, always, always going to get some sort of treatment, whether it's like standard, standard plus something new, or something really revolutionary that will give you the opportunity to be exposed to a treatment that is otherwise not available to the general public.

Host: Yeah. That is so helpful to hear. I feel like that is what I hear so much from patients. I heard about this clinical trial, but I'm not really comfortable with being experimented on and I think that's the real key message when we think about the work that we're all doing here and the clinical trials we're bringing to patients, is that really they are not being experimented on. We are actually testing drugs that have been tested before, and we're seeing how effective they are for treatments in comparison to protocol. Dr. Matei?

Dr. Daniela Matei: I would like to add that many of our patients are extremely generous. There is also the other side of the coin where patients want to help the women that come after them, and they know that participating in clinical trials will impact maybe not them. But the future patients with ovarian cancer or endometrial cancer, and I'm always personally very grateful to all these patients who maybe subject themselves to more testing and more blood draws so that we can further our knowledge and advance medicine.

Host: Yeah. Great shout out, Dr. Matei, to those patients that are really doing that extra work to really help all the patients around them.

Okay, guys, as we close up, let's talk about how patients get to you. How do they get to these trials? How can we do it? Already, Dr. Roque has mentioned all of his community outreach, amazing work that he's doing in order to get patients to like learn about the trials that might be available for our physician listeners, you know, how can they get people here working in a clinical trial? How can they figure out whether they're the right person to refer? Where do we go from here?

Dr. Emma Barber: Yeah. Yeah, I think a lot of this is, you know, sort of built-in relationships, right? But we also have a large network of Northwestern Medicine, right? And so, there's been a ton of work in increasing clinical trials, infrastructure, making sure that, especially sort of federal trials, things like that are available sort of throughout the health system so that a patient, if they, you know, are that rural patient that's living far west of the city, that they have a place, that they can go to get a clinical trial that's not coming all the way downtown.

We do still have, you know, some of the phase I studies, some of the really complex drug regimens, right? Those are only going to be downtown. But with the system, the goal is that even if you're coming to sort of, you know, anywhere in the Northwestern system that you know, tumors are screened, patients are evaluated to be able to say, "Hey, this drug matches your mutation. This is a really good opportunity for you," you know, then it may be worth sort of coming downtown. But we've really tried to increase the clinical trials infrastructure. Especially, for example, some of my trials more, than like 40-50% of the cohort actually comes from outside the downtown hub.

So, we want to really access those patients, make it be representative, right? Both to offer something to them, but also make sure that our results reflect, you know, real world, not just this downtown location.

Host: I mean, that's why I'm so excited that your role, Dr. Barber, has really expanded across the system to allow our physicians across the Northwestern system to really be able to refer down to you. And I hope you know, for anybody listening, our community partners out across Chicagoland, outside of the Northwestern medicine system, know that we're here for your patients. We're here to really help get them into these trials that really may benefit both their long-term survival as well as their long-term quality of life, looking at both our basic science and our clinical research. I'd love to hear any final comments for the group before we close out today.

Dr. Emma Barber: Yeah. I would echo, it's an amazing time to be a GYN-oncologist. The treatments we have, I mean, we all have stories of patients, you know, we heard so much about immunotherapy and trying to figure out how to make it work because when you see it work, it's amazing, right? Patients that have, you know, huge tumors, metastatic disease that are mine, that are totally cancer-free, you know, from immunotherapy. And so, I think it's just a really exciting time to be in our field.

Host: Thank you all so much for being here today. And thank you all for the work you do both clinically, on the bench, in the office, really caring for patients from the start of their diagnosis all the way through their journey and battle with cancer. Thank you all for being here today and thank you to our listeners for listening.