Melanie Cole, MS (Host): Welcome to AHN Med Talks, an informative resource for physicians across various specialties as we delve into the latest medical insights and best practices, ensuring you stay at the forefront of your field. I'm Melanie Cole. And today, our discussion focuses on the AHN Gynecologic Cancer Center of Excellence.

Joining me is Dr. Thomas Krivak. He's the Director, Division of Gynecologic-Oncology and Gynecologic-Oncology Research, and the Director of the Ovarian Cancer Center of Excellence at the Allegheny Health Network. Dr. Krivak, it is a pleasure to have you join us today. As we get into this topic, how has the landscape of gynecologic cancers changed over the course of your career? Have you seen the incidents of these cancers change in recent years? Tell us about what you see in the trends.

Thomas Krivak, MD: That's an excellent question. Thank you for this opportunity as well. So, the landscape has changed greatly. In the last 20 to 25 years, we've seen, unfortunately, the incidences of endometrial cancer increase, we've seen the incidence of ovarian cancer decrease. But really, what has changed is just the therapeutic approaches for these patients that have advanced stage endometrial cancer, advanced stage cervical cancer, as well as ovarian cancer. It's been very exciting these last five to seven years to see just so many clinical trials to see the investment in women's health and women's cancer health by numerous companies to develop these medications.

I would say that really at this point in 2025, ovarian cancer is treated with chemotherapy, debulking surgery, and then some types of maintenance therapy, whether it's going to be utilization of a PARP inhibitor or Avastin, or a combination of these treatments. And then, again, looking for endometrial cancer, we've seen, unfortunately-- like we talked about-- an increase in incidence of endometrial cancer, but we've seen improvements in treatment. Robotic surgery with lymph node assessment, so instead of making large skin incisions, we're making smaller incisions. Patients are healing quickly. And patients with advanced endometrial cancer or recurrent endometrial cancer are now being treated with chemotherapy, chemotherapy as well as immunotherapy, having a longer duration of treatment. And again, we're seeing improved response rates, improved outcomes. It's very, very exciting to take care of patients in this time, because we're having so many new and novel treatments come about.

And then, looking at cervical cancer, again, cervical cancer is a very rare disease. We have HPV testing, HPV vaccines, but we still have patients who present with cervical cancer, whether it's advanced or recurrent. And again, immunotherapy has made a tremendous impact in these patients.

I can remember being as a fellow, as a young doctor back in 1998, 2000, 2002, we didn't have a lot of opportunity for patients with recurrent cervical cancer or metastatic cervical cancer. Now, there are numerous opportunities: chemotherapy, chemoimmunotherapy antibody drug conjugates, such as Tivdak, which is an antibody drug conjugate, which can be used in the second line, has shown that we're giving these patients an opportunity for treatment. Twenty years ago, we didn't have a lot of opportunities for these patients, and now we do.

So, what I can say is the landscape has changed greatly with the majority of cancers that we care for in Gynecologic-Oncology. We have numerous clinical trials and the landscape continues to change rapidly. I feel very fortunate to work at Allegheny Health Network. We have excellent support for our clinical trials. We've participated in numerous clinical trials that have changed the standard of care for these patients. And it's just a great environment for us to practice. It's a great environment for us to engage our patients who get referred here to give them an opportunity for a lot of these cutting-edge medications. So, landscape has changed greatly and how we're talking about treating these cancers today. These patients with these cancers today is probably going to be different in six months, 12 months, and 18 months as well, just with all the innovations that's occurring.

Melanie Cole, MS: Well, it certainly is an exciting time in your profession. Dr. Krivak, what does it mean to be a center of excellence in cancer care? It's not something every hospital or medical center can claim. Tell us a little bit about the primary mission or overarching goal of the cancer center and why it's so important, why you are a center of excellence for gynecologic cancers.

Thomas Krivak, MD: I would say that you look at what are we focused on? We're focused on this population of patients who have Gynecologic-Oncology, and that's what we're focused on. Our clinical trials are focused on that, our surgeons are focused on that, including myself. Our pathologists are focused. We have gynecological pathologists. A lot of our pathology, a lot of surgeons that we do at some of our outreach institutions will get reviewed here. So again, it's a multidisciplinary approach with numerous people. And this includes having patients coming in from West Virginia, Ohio, New York, into West Penn, into some of our regional hospitals and just having excellence in nursing care, having private rooms, allowing us to provide this care in a compassionate manner, in a private manner, so that they feel like they're getting one-on-one care from their clinician as well as their nurses, as well as having nurse navigators in this part of being able to provide comprehensive care.

So, to me, the Cancer Center of Excellence, the Gynecologic Cancer Center of Excellence, really is just saying that when you come to us, we're going to focus on women, women's health, women with gynecologic cancers. And everybody in our institution here is focused on delivering compassionate care, as well as the most up-to-date, cutting-edge care. And really, that's what we're trying to strive for at AHN within the division.

Melanie Cole, MS: Well, thank you for telling us that. Now, let's talk about some of the exciting innovations in the treatment of gynecologic cancers. Why don't you start with robotic surgery and how that's really broken onto the scene and changed a lot for women undergoing these types of surgeries?

Thomas Krivak, MD: Absolutely. I think robotic surgery, again, we go back, you asked me about the landscape. I finished my fellowship in 2002. We didn't even have the robot then. I had to get trained in the robot in 2009, 2010, and then develop these skills. And we've seen it just kind of multiply. I can still remember having to make large skin incisions, wound infection rates higher, have to remove numerous, numerous lymph nodes.

Now, we have sentinel lymph nodes where we can inject the surface and inject the uterus and be able to tailor our lymph node removal to decrease operative time. We have puncture incisions, small incisions about the size of your index finger, the nail tip there, five to eight millimeters. Again, these patients can recover quickly, lower wound infections. And if unfortunately they have advanced stage disease, that allows them to recover quickly, so they may move on to the next therapy, whether it's chemotherapy, immunotherapy, radiation, or combination of those treatments.

So, I would say that when I look at my career and say, wow, we would have five or six patients admitted to the hospital because they would have wound infection from these large skin incisions, we don't see that anymore. And again, patients are recovering quicker and they do like that because, again, it's not just about wound infections, it's about getting back to your quality of life. "I'm a teacher, I want to get back to my students," "I'm a mother, I want to get back to my kids. I want to be able to drive them to their practices. You know, I want to be able to help around the house and do kind of things and enjoy my life." So really, it's about quality of life, getting on with your treatment, those kind of things. So, robotic surgery has really been a game-changer in patients with endometrial cancer as well as ovarian cancer. And we're blessed, I think we have seven robots at West Penn and have an excellent robotic program.

Melanie Cole, MS: Wow, it really is amazing how you've seen it transform over your career. Now, what about things like immunotherapy? Because that is really an exciting part of your profession, Dr. Krivak. Speak about immunotherapy for endometrial cancer, and you were talking just a bit about cervical cancer and the advent of HPV vaccines and HPV screening and how that's really also changed the landscape of cervical cancer, but you are still seeing it. So, speak about how you're using immunotherapy for these cancers.

Thomas Krivak, MD: Immunotherapy is definitely a game-changer, no doubt about it. When we looked at the trials, and most of the people listening to this podcast are going to have read the trials that combine Keytruda with chemotherapy, dostarlimab with chemotherapy, and then get prolonged maintenance, as atezolizumab, durvalumab. All these studies were positive studies that showed the majority of these patients had improvement in response rates, duration of response, as well as improvement in progression-free and some trials showing improvement in overall survival. So again, improving access to care, improving these patients to be able to get immunotherapy is really important.

When I talk with patients about immunotherapy, I kind of tell them it's like hijacking your immune system. You're going to get exposed to this medication that kind of hijacks your immune system to have those T cells go back and attack those cancer cells. So hopefully, they'll provide on longer duration of response. And that's what we saw in endometrial cancer and as well as for cervical cancer, again looking at patients who had metastatic disease to the lungs of the liver, things of that sort.

When I was a young doctor, 2002, 2004, we had short responses, few responses with chemotherapy. Now, we're seeing some patients have durable responses. We're having the immune system go in and attack and having some memory there. So, these patients have long, durable responses. So to me, immunotherapy is really a game-changer for patients with endometrial cancer.

Cervical cancer, unfortunately, it's fallen short a little bit ovarian cancer, but we're still working on that. And we do, we need to continue to make progress with these. Immunotherapy hasn't cured everybody. So again, clinical trials are still very important. Just like I said, I love being at AHN, because we can do clinical trials because not everybody gets cured. It's a much higher percentage, but again, game-changing. When we see patients, we don't want them to have advanced cancer. We want to get in the pre-cancer, early cancer. But if they have advanced or recurrent cancer, we know we have effective therapies that they can undergo. And we know that we have effective opportunities for clinical trials that will compare the standard of care to potentially more effective treatments.

So, to me, immunotherapy is a game-changer. And again, if somebody's going through their cancer journey, if they're not being offered some of these medications, they really need to get on the internet and they need to think about it. Any of the providers out there can reach out and give us a call to be able to talk to us about this. But to me, I think it's an outstanding opportunity for our patients who have recurrent or advanced disease in the endometrial cancer or cervical cancer setting.

Melanie Cole, MS: Dr. Krivak, tell us about novel antibody drug conjugates for Gynecologic-Oncology. Let other providers know the exciting work you're doing at AHN.

Thomas Krivak, MD: Yeah. I mean, antibody drug conjugates are a game-changer, just like immunotherapy. Again, these things are rapidly evolving. We have HER2-based therapies. We have tissue factor-based therapies, folate-targeted therapies, Trop-2-targeted therapies, and there's others coming, CDH6.

So, we look for differential expressions as everybody knows, and then we try to develop a target to those. And they're developing these targets, these novel targets that hopefully are differential expressed in cancer versus standard, or regular cells. And we're seeing delivery of these medications, these payloads into higher concentrations into the tumor, as well as having a bystander effect. So, we have novel targets. Some of these require biomarker-driven, some of them don't. And again, we're on the five-yard line here of understanding some of these medications and we've got 95 yards to go. Very exciting. Utilizing in HER2, in 3+ and 2+ patients who have endometrial cancer, cervical cancer, ovarian cancer, I've seen some dramatic responses. I talked about Tivdak for cervical cancer, very, very exciting antibody drug conjugate. And then, mirvetuximab is very, very exciting for platinum-resistant ovarian cancer.

Again, three antibody drug conjugates that are FDA approved for the treatment of these patients with cancer, and have showed dramatic responses in some patients. And again, it's all about giving these folks an opportunity. It's all about giving our patients an opportunity. We have trials looking at Trop2 antibody drug conjugate as well. And again, very exciting seeing some incredible responses when comparing this to standard chemotherapy.

So, these are going to continue to rapidly develop as we all go to our conferences such as ASCO or SGO, these meetings. We're just seeing numerous medications. And it's really nice to see the investment from the pharmaceutical industry in women's health as well as the investment, again, in AHN because this takes time. It takes physician time. It takes clinicians time to allow us to have this time to develop these clinical trials with pharmaceutical companies, as well as with the government to bring these trials to our patients.

Melanie Cole, MS: Well, there's certainly so many exciting advancements in your field, Dr. Krivak. But one of the more important things I feel for patients and for providers because it adds benefit to both, is the multidisciplinary team and how it's so ideal for managing some very complex patients. I'd like you to speak about your team, including the role of nurse navigators and how they can really help patients navigate that very dizzying world of cancer care.

Thomas Krivak, MD: Yeah, that's a great point. Teams accomplish much more than individuals. There's no doubt about that. So when I look at our team at AHN in multidisciplinary, I agree, it's nurse navigators, which play a tremendous role, because healthcare is so complex. Sometimes I look at it and think, if I had a partner who was going through one of these treatments, could I actually navigate her through that? And so, it's nice having a nurse navigator who can come in and see a patient, say, "Hey, listen, I know we talked about chemotherapy, radiation therapy, ports, genetic counseling. I'm going to help walk you through this." The doctors and the nurses and the APPs are going to talk about this, but we're going to help get you your appointment to get your port placed. We're going to help get your appointment to make sure that you're getting your chemotherapy education and understanding where you're going for that, as well as followup for your genetic counseling. So, nurse navigation, I think, is one of the most important things. This is a phone number the patients can call when they get confused or when they feel overwhelmed.

Again, important part of our team are APPs, you know, our advanced practice providers. We have folks in our office that help with the chemotherapy with all our clinical trials. Donna Kinzler is absolutely wonderful. She's great with the patients. She helps manage all our patients on clinical trials, chemotherapy, chemotherapy side effects. Again, looking at what else is in the multidisciplinary team. Nurses, our hospital nurses are very important. Our pathologists are very, very important. Our collaborators in Radiation Oncology are very important. Our Medical Oncology colleagues, because everybody can't be treated at one institution. So, some people are being treated with Medical Oncology in the community, which is absolutely wonderful. And then, we come together with a tumor board where we sit down and review patients. And at times, what's really, really nice is that our colleagues can call into the tumor board, have cases presented that are complex. So, we can all look at CT scans, look at PET scans, look at pathology, look at what they've been through to help kind of give additional advice to help treat those patients.

So, to me, it's a large multidisciplinary team, which again is always hard to navigate. Having that nurse navigator up top, having a physician assistant or the nurse practitioners helping us care for these patients so they have people to call if the doctor's not available or in surgery to talk side effects, to talk side effects of chemotherapy, as well as having our clinical trials research team. A lot of times we'll say, "Hey, this patient looks like may be a good clinical trial candidate." We'll talk with the patients about it, but they'll be able to reach out to the clinical trials team as well as the nurses to ask further questions as well as ourselves. So to me, I think a lot of this is very, very important.

I can use an example that we have a patient who is on the RAMP 301 trial, which is a trial evaluating two novel medications for a very rare disease called low-grade serous ovarian cancer. Most ovarian cancer is high-grade, a small percentage is low-grade, and it can be a slow indolent type of cancer to treat, and it was a multidisciplinary approach that identified the patient. I talked with the patient about the clinical trial week, have her enrolled in the clinical trial. And then Donna Kinzler and myself and the team kind of helped manage her through four cycles of treatment. She's had some side effects. We helped mitigate those side effects. But she's had a fall in her C-125, and she's had almost a complete response on her CT scan after about four treatments.

And again, that's very, very incredible because this disease was slow, indolent, not a lot of treatment opportunities. We opened the clinical trial. We saw how this medication worked. She got on clinical trial, she randomized to the investigational agents, and our team here was ready to get her treated about this. And I think we were the first site in the United States to open this RAMP 301 trial. So again, that's a true team effort, which provided excellent care and excellent opportunities for the patients in Western Pennsylvania that suffer from low-grade serous cancer.

Melanie Cole, MS: Well, while we're on the subject of clinical trials, I'd like you to tell us about the HOTT trial for ovarian cancer and hip at the time of surgery, and any other cutting-edge clinical trials that you would like to mention.

Thomas Krivak, MD: Absolutely. The HOTT trial, I think, is very, very important. We've utilized heated intraoperative chemotherapy for a long period of time. And again, we need to do the trials to say half the women are going to get it, half the women aren't. And do the women who receive heated intraoperative chemotherapy, do they do better? Do they do the same? Or potentially, do they do worse? Again, when we look at a phase III trial, we're looking at outcomes to include increased response rate, increased progression-free survival, increased overall survival. But we're also looking at side effects. Is the surgery too debilitating? Is the intraoperative chemotherapy for 90 minutes too debilitating?

So, this trial randomizes patients to receive heated intraoperative chemotherapy, cisplatinum versus none. It randomizes them at the time of surgery. So, we consent the patients, we take them to the surgery, we do the debulking surgery. Once we know that they're optimally debulk, they're going to be randomized. And then, after surgery, they heal in the hospital, they get their additional chemotherapy, and then they go on to maintenance treatment. Maintenance treatment is that low dose treatment, that extra treatment for another two to three years. This trial utilizes niraparib for three years. And so to me, I think it's a very, very important trial in that patients get treated aggressively with chemotherapy, debulking surgery. Half the women are going to get heated cisplatinum during surgery, the other half aren't. And then, patients are going to be on niraparib for two to three years.

This trial really, really is important to help look at, is it the medication and the drug delivery of the heated intraoperative chemotherapy? Does it improve outcomes as well as look at the side effects? Because again, it adds about two hours worth of surgical time to two and a half hours worth of surgical time for these patients. So, I think that's an outstanding trial. I'm glad the GOG is doing it. I feel privileged that we're able to participate in it.

I already mentioned the RAMP 301 trial for low-grade serous cancer. I would say anybody who has a patient who has a low-grade serous ovarian cancer, if they're looking for a clinical trial, the two novel agents in this trial are very, very interesting and appear to have a great response rate from the previous trials that have been done. I am more than happy to see them at AHN, so we can consider enrolling them on trial.

And again, looking at Trop2, I think Trop2 is a novel antibody drug conjugate. And again, looking at trials that are evaluating Trop2 expression and Trop2 antibody drug conjugates for endometrial cancer patients, cervical cancer patients, as well as ovarian cancer patients. That's the next thing that we're looking at.

So, we have clinical trials available for all those patients. And it's really so exciting to have numerous clinical trials that appear appear to be so effective in the phase I and phase II realm that we're removing into phase III, that these are just so exciting to be a part of. Very, very exciting to be able to offer these to our patients.

Melanie Cole, MS: Wow, that is exciting. And Dr. Krivak, you've given us so much to think about. My goodness. Before we wrap up, I'd like you to speak about how the center ensures that patients and their families are supported throughout this treatment. You've told us about the multidisciplinary team. You've told us the importance of the nurse navigators and all the exciting trials and innovations going on in gynecologic cancers. Speak about the focus on patient-directed goals of care and quality of life, because certainly keeping cancer patients alive is paramount, but the quality of life is also of utmost importance. Can you just give us a little summary of what you've spoken about today, the key takeaways and why that is so important for these patients?

Thomas Krivak, MD: Absolutely. Quality life's the most important thing. We're having cancer successes with treatments. We want to make sure they have a good quality of life. The multidisciplinary approach is very, very important. The team approach, very, very important. And again, everything is focused on the patient. Advanced practice providers helping us with patients.

We do have an ambassador program that is connecting cancer survivors and people going through treatment to help give supportive care for those folks. It just initiated, it's a huge initiative. Again, because sometimes when people are going through cancer, they want to have people to talk with, people who understand what they've been through. And so, we've instituted this program as well. And really, it always boils down to the patient. Everything that we do, we look at the patients who wants a clinical trial, who doesn't, who wants to be treated at West Penn, who wants to be closer to home and get them treated closer to home, what is the best thing for the patient and the family? That's is the first question that we all want to ask when we see that patient.

And you're right, you know, having programs that talk about survivorship, having survivorship programs that we do every now and then to allow people outside the office to talk to their doctor, to talk with other patients is tremendously important. Having classes, cooking classes that they can have at AHN Wexford, the hospital there, and looking at complementary things that some patients want, some patients don't.

So really, as we go through this cancer journey, it's just an awesome experience for me as a clinician, I feel so privileged to take care of these patients. Anytime a patient chooses me to be their doctor, it's like a huge compliment as I get to kind of go through this journey, and this journey is very different for each patient. And it's our job as clinicians, it's our job as the multidisciplinary team to figure out how to best guide that patient, that family, through that journey.

Melanie Cole, MS: Wow, Dr. Krivak, I can certainly hear the passion in your voice for what you do for a living and the compassion for your patients going through these very scary cancers. Thank you so much for joining us and sharing your incredible expertise with us today about all the exciting things in your field. And to learn more or to refer your patient to Dr. Krivak at AHN, please call 844-MD-REFER, or you can visit ahn.org. Thank you so much for listening to this edition of AHN Med Talks with the Allegheny Health Network. I'm Melanie Cole.