BY ERIN O'DONNELL | PHOTOS BY DAVID SZYMANSKI
James C. Thomas, M.D., Ph.D.
Oncologist at Froedtert & the Medical College of Wisconsin (MCW); section head of solid tumor oncology at the Froedtert & the MCW Clinical Cancer Center; medical director of the Froedtert & the MCW Cancer Clinical Trials Office and the Translational Research Unit
Years of practice
How does Froedtert’s Translational Research Unit help people with cancer?
We wanted to increase our first-in-man and early phase clinical trials, and felt this required a dedicated treatment or infusion area. These are compounds and ideas that look great in the petri dish and in mice, but you’re potentially trying them on human beings for the first time. Despite all the extensive testing, you have to be very careful because human beings aren’t mice. You have to start at a lower dose and monitor them carefully to make sure they’re not having unexpected side effects. You also need to measure whether the compound is getting to the right level. A lot of times we’re trying to prove that the compound is doing what it’s supposed to do. If it is a targeted agent, we need to show evidence that it’s affecting the target, and so we need extra science — extra lab-based studies on blood samples or tumor biopsies to show that the new drug is having the effect that we would expect.
How many hospitals have a dedicated area just for early phase trials?
There are no others in Wisconsin that we know of. But I think it’s going to be a growing trend at academic centers. We were one of the early adopters of this as a concept.
Why might a patient choose to participate in an early phase trial?
We usually have upward of 150 treatment trials at any one time, and they span the gamut from early phase trials to concepts that are farther along. This is basically a way for patients to get tomorrow’s treatments today. These treatments might not be FDA approved for years, so the only way to get access to those drugs now is to participate in a clinical trial. Certainly we have data that shows that people in clinical trials do very well. These concepts, although new, are extremely well vetted. And a lot of people battling cancer are very motivated to be a part of the process to improve things, to help come up with new treatments. Maybe it won’t help them, but it might help the next person who comes into the clinic. People often take that to heart and think it’s an important way to help.
Can you describe an early phase cancer trial that you’re particularly excited about?
We recently had our first-in-man treatment with a chimeric antigen receptor (CAR) T cell. We take a white blood cell out of your body and genetically manipulate it so that it will attack the cancer. We grow a decent-sized number of these cells and infuse that back into the patient, and then the white cells go after the cancer. This is a new kind of immune therapy that’s very exciting. We have a number of trials with CAR T cells, but this particular CAR T cell is actually something that we developed. We hold the new-drug application and are working with the FDA on it. It’s really our baby. Right now we’re using it for leukemia and lymphoma.
There’s another first-generation CAR T cell that’s been FDA approved, but it’s a very expensive therapy; it can cost upward of a half million dollars. Our therapy involves genetically manipulating these cells on site such that they will attack the cancer cells. We can generate these cells quicker and much more cheaply at our facility. It offers the promise of making this available to more patients at more centers. We’re really pioneering this as a concept.
What would people be surprised to learn about you?
I did some stand-up comedy when I was younger, here in Milwaukee during my residency. I also make a mean chocolate-covered caramel apple. When I had my first Honeycrisp apple, I realized that this apple was meant for bigger and better things. I did a lot of experimenting to come up with my recipe, and now it’s my Christmas present for everybody.
Amy Wagner, M.D.
Pediatric and fetal surgeon, Children’s Hospital of Wisconsin (CHW); co-director of the Fetal Concerns Center at CHW; associate professor, Medical College of Wisconsin (MCW)
Years of practice
What is the Fetal Concerns Center at CHW?
The center was developed in 2000 to offer counseling and other services to women diagnosed with any type of abnormality of the fetus. I was recruited in 2011 to start a fetal intervention program. Since 2011 we’ve worked to offer both minimally invasive and open fetal surgery. We offer individualized compassionate care for the entire family, including medical treatment for whatever diagnosis the fetus has, as well as monitoring, and in some cases, fetal surgery. We also coordinate delivery and any surgical care, and any other medical care that would be required by the baby after delivery. There’s only a handful of programs in the country that offer the entire gamut of fetal intervention — probably a dozen at most.
Could you describe one of the problems you address with fetal surgery?
We have done 10 open fetal surgeries for spina bifida since 2014. We’re evaluating a patient next week whose fetus has spina bifida, which is a problem with the spine being exposed. She’s coming to see us because she’s a candidate for fetal surgery to repair the spine of the fetus before birth. There’s research that shows that repairing the spine before the baby’s born allows them to have fewer medical problems after they’re born. The changes in the brain that go along with spina bifida can reverse, and we can see their brain actually normalize while they’re still in utero.
How does fetal surgery differ from other types of surgery?
We have at least two patients: the mom and the fetus. Sometimes we have three patients at once, because the most common fetoscopic operation we do is for twins. The most complex part of my job is coordinating all the physicians around the operating room table for open surgeries. The mom has an anesthesiologist. The fetus has an anesthesiologist. I’m there, as well as the maternal fetal medicine provider, the neurosurgeon who does the actual work on the spine, and then a fetal cardiologist, who watches every single heartbeat throughout the entire operation. There’s not a lot of space. It’s so much teamwork and coordination. But honestly that’s one of the things I love most. We have the most extraordinary team of physicians who are entirely dedicated, helpful, compassionate and just outstanding doctors. It’s an honor to work among all of them.
It’s amazing to think that fetal surgery is possible.
I know, right? I am totally with you. I did some of my training in San Francisco with the “father of fetal surgery,” Dr. Mike Harrison.* I always think about that — How did he have the courage to say, “I can open a uterus and fix the fetus and close the uterus and everything will be OK?” To be clear, he did it on a lot of animals first. But to even think that humans could tolerate that is just astounding. I’m so glad he had the audacity to do that.
What is the biggest challenge of your job?
By far the biggest challenge is keeping balance in my life. My job can be pretty consuming in a lot of ways. I have two children and a husband, and, you know, I’d like to have some semblance of balance.
I understand that you’re a Wisconsin native.
Yes, I grew up in Waukesha. But I was completely surprised to end up back here. I despise the cold weather and did all my training on the West Coast, in Seattle and San Francisco. My husband was born in California. I convinced him to come to Wisconsin for what we thought was two years, so I could do my pediatric surgical training here. (The fellowship through MCW, which includes practicing at CHW,) is one of the best, if not the best, pediatric surgery training programs in the country. And when they offered me a job to start a fetal intervention program, it was a dream that neither of us could refuse. I just loved being in this hospital. How could I not want to work with these people every day? By that time my husband said, “Why don’t we just stay in Wisconsin? It’s such a nice place for our kids,” so he really likes it here too.
What would people be surprised to know about you?
I’m a secret Bikram yoga addict.
*Editor’s note: Dr. Michael Harrison performed the world’s first open fetal surgery more than 35 years ago at the University of California, San Francisco.
Robert Roth, M.D.
Interventional cardiologist and medical director of the Cardiac Catheterization Lab, Columbia St. Mary’s, part of Ascension; lead clinic physician, Columbia St. Mary’s Cardiovascular Specialists, part of Ascension
Years of practice
What do you find most exciting about your job?
The great thing about this job is that it’s always changing. I do things now that I could never have conceived of when I finished training. Cardiology is always at the forefront of the developments in medicine.
What would you like people to understand about their heart health?
I think the biggest thing is the patient’s responsibility. I see caring for people as a partnership between myself and the patient. My responsibility is, number one, educating people as to what their disease is and how to deal with it. They really need to understand that lifestyle modifications can significantly impact their disease.
Medications and balloons and stents really are secondary to lifestyle modifications: diet, exercise, healthy lifestyle choices, no smoking and all the things that we educate them about. Prevention is paramount.
Ascension is working to develop national service line Centers of Excellence. What does that mean for patients?
Columbia St. Mary’s is now part of Ascension, and we’re bringing together four legacy health systems across Wisconsin. In greater Milwaukee that includes the Columbia St. Mary’s and Wheaton Franciscan Healthcare systems. As part of Ascension, we are part of the largest nonprofit health system in the country. Twice a year I meet with cardiologists from other Ascension hospitals across the nation. We share best practices, compare cases, data and more. As a result, Wisconsin patients are getting the benefit of the best cardiologists across the country, right here close to home. The specifications for a cardiology center of excellence come from the American College of Cardiology and the American Heart Association, and involves delivering the highest level of care in the most efficient way possible. As we do that, we want cardiology patients to have access to our entire integrated system of care, no matter where they live. If a patient enters the hospital in Merrill and has a heart rhythm abnormality that the physician doesn’t know how to treat, that physician has direct access to other Ascension Wisconsin physicians across the state. We’re using telemedicine and electronic health records to support this. That physician in Merrill now has immediate access to a heart rhythm specialist in another part of the state, who can see the heart rhythm in real time and consult directly with that physician.
How can this information-sharing benefit patients?
Here’s one example: Several years ago, through our data registries, we found that we had patients who had bleeding complications after interventional cardiology procedures. We looked at it locally and couldn’t find a single reason for that. Going to one of these national meetings, I found that other hospitals were having similar problems.
Most cardiovascular procedures historically have been done from the groin, in the large artery right in the top of the leg. The problem is that’s a large artery, it’s under pressure, and bleeding complications can be life threatening. So a cardiologist in Indiana had begun doing the procedure from the artery in the wrist, right where you feel your pulse. I took a representative group down there, including nurses and other people that worked in our cath lab, and we learned the procedure and brought it back to Columbia St. Mary’s. All seven of our interventional cardiologists now do their procedures primarily from the radial artery. Our patients directly benefit from it. They need no bed rest after the procedure. They can walk out of the cath lab. We have very few bleeding problems from the wrist.
What would people be surprised to learn about you?
One of my hobbies is collecting and repairing antique fountain pens. I got into it because of my grandfather, who always believed in the beauty of the fountain pen and taught me to write. I still carry one and use it whenever I can. I like to distinguish myself from other physicians, because you know the reputation of physicians and handwriting. When I get the opportunity, I like to take my time to write something.
Susanne Krasovich, M.D., (left) and
Maureen Longeway, M.D.
Family medicine, family medicine with obstetrics
Family medicine physicians, ProHealth Care; faculty, ProHealth Family Medicine Residency Program in Waukesha
Years of practice
21 (Krasovich), 8 (Longeway)
You are currently developing a new pregnancy and substance abuse program, scheduled to launch this spring. Why?
Krasovich: We’ve noticed over the years that we have quite a few babies who end up requiring care in the neonatal intensive care unit (NICU) for opioid withdrawal after birth. We’ve also noticed that we have more and more patients, both pregnant and not pregnant, who have substance use disorder and really have limited options for getting help.
Longeway: As family medicine physicians who also provide obstetric care, we take care of women and deliver their babies as well. A lot of times we found that although these women could obtain obstetric care, the obstetricians were less familiar with care for addictions or opioid use. And many internal medicine physicians and even addictionologists are less comfortable managing pregnant women. And so these women really found themselves in a bind. We’re both fully trained in obstetric care, so we know how to manage normal and high-risk pregnancies. At the same time, we also have training in adult medicine and addiction issues, so we are in the one field that addresses both sides of that problem.
What can your program do to help pregnant women with addictions?
Krasovich: The first thing is making sure all providers throughout our system who take care of pregnant women are talking to patients about this issue. It can be a hard conversation —both from the woman’s end and the physician’s end. So we want to do some training and support to help people have those conversations. We’re hoping that we can identify patients earlier and help move them toward treatment through pregnancy.
Is your goal to help pregnant moms quit opioids?
Krasovich: That’s a common misconception. People think the best thing would be to just get them off whatever substance that they’re on, but actually that’s really dangerous for pregnant women. Instead we want to get them into medication-assisted therapy to stabilize things. We want them to stop heroin or oxycodone, and get them onto a safer option like buprenorphine.
We need to think about this almost like a chronic disease. We want to make sure that we identify these women, help get them into treatment if they’re ready, get them a safe pregnancy (and) a safe delivery, but then make sure that we’re providing the lifelong care that will help them be as successful as possible.
Longeway: Family medicine is uniquely positioned to handle this problem and to handle it well. And as a residency program, we are the primary trainers for the area’s family medicine doctors. We also can tailor addiction treatment to the needs of a mom and young baby. We were finding that most treatment programs are built for adults who don’t have newborns. Spending eight hours a day in treatment if you can’t bring your baby is just not feasible for young moms.
(It doesn’t allow them to breastfeed or bond with their babies) — things that are evidence-based methods to improve outcomes for these babies and moms.
What else do you want to accomplish with this program?
Krasovich: We would really like to see fewer babies needing NICU-level care because of significant withdrawal.
What do you want people to know about substance abuse?
Krasovich: If you are trying to live with and work through substance abuse, it’s absolutely something that you can and should talk about with your provider. There are providers who are willing and able to help you, in the same way that we’re able to help people with other challenging, difficult problems.
Longeway: I think a lot of people feel a hopelessness that there isn’t anything to be done, or they think the provider will judge them and won’t be able to do anything for them. But there’s a lot to be done, and people can live with addiction just like they would live with a chronic disease. It doesn’t have to be life-limiting. It really doesn’t.
What’s your ideal winter day when you’re not working?
Longeway: I am kind of a city girl when I can be. And I really enjoy the Milwaukee Art Museum in midwinter. I like soaking up the art, looking out over the frozen lake, and then having some hot coffee somewhere.
Krasovich: My perfect winter day would be about 20 degrees and sunny, with at least a few inches of snow on the ground. I would get outside for a late-morning run or strap on snowshoes and tromp around. I’d spend the rest of the day with my husband and kids doing something we all like to do together, like take in a Broadway show, a movie or a sporting event. We would meet up with extended family or friends for dinner at Fortune (Chinese) Restaurant. There would also be hot chocolate involved.
George Bobustuc, M.D.
Neurologist and neuro-oncologist, Aurora Health Care; medical director of Aurora Health Care’s neuro-oncology program
Years of practice
What is the Aurora Research Institute?
It’s the research arm of Aurora Health Care. Aurora Health Care has a long history of research and currently has 500 research projects, including 300 active clinical trials — mainly in the areas of cancer, neurosciences and cardiovascular medicine. The Aurora Neuroscience Innovation Institute focuses on researching brain cancer and neurodegenerative diseases.
How is your research attacking the problem of cancer?
Most of our work is driven by our view that cancer is not a chaotic event, but a structured response to a chronic, out-of-proportion stressor.
We think there are some common pathways supporting tumor growth across cancers. We try to understand the commonalities across cancers, which is different from what other researchers are doing today.
We are trying today, using more and more advanced tools to go through a crash site (and) using a philosophy that puts us at a disadvantage. Think of tumor tissue as a crash site on a highway. You have a bunch of cars that are really looking bad, and you’re trying to figure out which car started the accident. You might think, “That big blue truck probably started it because it is turned around 180 or 270 degrees.” But we don’t really care what started it, or how bad the crash site looks. What really fuels the growth is not what started it. It is the multitude of signaling pathways supporting growth — functions that rely on separate groups of genes, which we are not routinely looking for when we do next-generation sequencing.
There are certain groups of genes that support tumor growth across cancers. We want to manipulate those genes in smart ways to stop growth, stop migration (and) stop new vessel formation. These actors in these pathways are not coded into our DNA to give us cancer, but to help us develop from an egg to an embryo and so forth (and) support specific, specialized functions in normal cells. This is the key to the cure: (which) set of common genes are involved in allowing a normal cell (to) activate pathways already coded into our DNA that support cancer growth. The initiating event — be that a germ line mutation or a spontaneous one or a virus pushing the wrong genetic/gene expression buttons — is not all that important to cure cancer. This is how our basic science research philosophy is different.
Given the commonalities across solid tumors, I think treatment will rely on several smart combinations of drugs that will be very easy to use, which will effectively stop abnormal signaling in cancer cells across cancers. It is as if you take the electric grid down and leave the whole town in the dark. A sort of a rapid fire e-bomb, if you wish. You do not need to know much about what is in front of you to take a grid down using an e-bomb. So (the) key is to design smart, small RNA molecules that would create the equivalent of e-waves and stop signaling in tumors. This is what will make them vulnerable to very small amounts of chemotherapy. When thinking about cancer this way, you could imagine that someday cancer will be treated by primary care physicians in their office by choosing smart combinations of drugs.
What kinds of drugs are you combining, and why?
We’ve learned in the lab that when we slow down cell signaling, we make tumors significantly more sensitive to chemotherapy and can use chemotherapy at significantly lower doses. For example, disulfiram, also known as Antabuse, is a drug that has been around for (more than) 60 years to treat alcoholism, but it turns out it inhibits key enzymes that are important to our approach. When we add a small amount of copper to disulfiram, we can make a fairly chemo-resistant aggressive brain cancer more sensitive to chemotherapy and radiation.
When will patients benefit from your research?
Some of my patients have already benefited. Because these medications are already approved, we can use them off-label in patients who do not have any other choices when standard of treatment fails. We also just began a trial in which we offer this treatment up front to patients with brain tumors known as glioblastoma multiforme.
What does your job involve on a daily basis?
I wake up thinking about my patients, and thinking about strategies for their problems. And I come in to the hospital and start seeing patients in the clinic and on the floor. And then I go home and keep thinking about it. We do a lot of work interpreting what is happening to patients based on their MRI findings, their laboratory values and their side-effect profile. That’s key to our approach of tailoring the combination treatments to the patient; we adjust doses and frequency of treatment to the patient.
What is the biggest challenge of your work?
Delivering bad news is probably the toughest. Patients have their scans in the morning and then walk over to the clinic, and I talk to them about the scans.
I check on the scans before I go in and collect myself to make sure that I can deliver that news in the most compassionate and, most importantly, the most constructive way.
Describe your perfect winter day when you’re not working.
I have two Pulis. These are Hungarian shepherd dogs. They’re sisters, and their names are Kinga and Reka. They really like snow, and so I would love a day outside with my dogs and lots of snow. We would probably spend hours outside.
Tell us something fun about yourself.
While I don’t have kids, I really like to interact with my young nephews and nieces. One summer while they were all visiting their grandparents in Romania I actually dressed up as Santa and pretended I was lost. They were asking all these questions about how I got there and why I was lost, and they were very concerned about me not being on time for Christmas.