Collaboration is advancing cancer research in Cincinnati

At the forefront: University of Cincinnati Cancer Center

An emphasis on collaboration is helping make Cincinnati a leader in cancer research, according to two local experts. We sat down with those doctors – Dr. William (“Bill”) Barrett and Dr. Andrew Frankart – to learn about the current state and future of cancer research here, and how changes in funding might impact that future.

Barrett is a radiation oncologist at the University of Cincinnati Cancer Center; professor and chair of the radiation oncology department at the UC College of Medicine; and medical director of the Barrett Cancer Building (named after his father, who had the idea for such a center). After starting as an orderly at the hospital 46 years ago, he has now been on the faculty for 33 years. About half to two-thirds of Barrett’s time is spent seeing patients; the rest of his work involves “administratively trying to have the atmosphere where everybody working here can thrive and perform at their best.”  

Frankart is an assistant professor in Barrett’s department. Born and raised in Cincinnati, he did his undergraduate, medical school and residency through the university, where he’s now on faculty. He divides his time evenly between pediatric radiation oncology at Cincinnati Children’s and his cancer research efforts. 

What made you want to go into medicine in general and cancer research more specifically? 

Barrett: When I was in medical school, I liked really every specialty, and really could have done anything. From the job that I had as an orderly, which was between sophomore and junior year in high school, I realized right away that I really, really wanted to be a doctor if I possibly could be. During medical school, you have the opportunity to rotate all different specialties. I liked everything, and I came across this field. Radiation oncology has a lot of variety … and it’s a significant problem. It’s not a trivial thing. People face life-threatening and life-altering diseases. The opportunity to try to be helpful, however possible; to help people be cured, whenever possible; and to be able to provide the atmosphere where, rather than people suffering and being humiliated by the disease, (they) can maintain grace and dignity and comfort throughout. It’s been a great specialty. 

I always tell the medical students, you really can’t go wrong with any specially of medicine. They’re all wonderful specialties. But this one, particularly the relationships we’re able to develop with the patients, it’s pretty special. 

Frankart: I would echo for my journey as well, that being a doctor is really the only thing I’ve ever dreamed of being. So this is a fulfillment of that dream, being able to be here.

Then, particularly as it relates to oncology, I had family members who went through cancer treatment, so I saw that personal side of what it means for someone to go through that journey. As I went into medical school, (I) knew that oncology was the direction I wanted to head, but honestly wasn’t aware of radiation oncology as an option. 

I did a rotation in the department here, where we get to see all the different aspects of oncology, with surgery and medical oncology, radiation, pathology, everyone who’s involved in the care of these patients. Radiation oncology is the one that resonated with me most, probably on two levels. One, on the intellectual level, I like the math and the physics that’s involved with it, the fact that it’s discrete, and you can calculate doses and know exactly what’s happening for a patient plan. The problem-solving that goes with that really appeals to me. Then, more importantly, (there’s) the emotional support Dr. Barrett alluded to that we provide to not only patients, but their families who are all going through this journey together. I have a particularly special place in my heart for kids going through that journey, and that led to selecting that as my focus within radiation oncology. 

I consider it a real privilege to be someone that, hopefully, these families can trust in hard times and know that they can rely on, for me to do the best possible job I can, (for) every patient that comes through the door. 

What are some of the most significant research projects that each of you has worked on in the past? 

Frankart: My broader interest, with the support of the grant (from the American Cancer Society and American Society for Radiation Oncology, or ASTRO) is spatial fractionation. Basically what that means is, normally, we treat tumors to the same dose, trying to have uniform coverage across the entirety of it. With spatial fractionation, we’re intentionally having very, very high-dose regions within a tumor, as well as introducing lower dose regions within a tumor, ideally allowing us to treat larger tumors than we normally can; minimize side effects; and then leverage some of the biology involved with that. The grant is supporting a clinical trial that’s ongoing, and the only one in the region offering that type of therapy.

I have a couple of other trials ongoing in development that are looking at using imaging and then immune correlates to optimize that type of radiation. 

Through my role at Children’s, I’m additionally involved in flash radiation – ultra high-dose radiation – and finding novel applications of that, in which we’re a global leader as an institution. 

What would you say is Cincinnati’s position in terms of cancer research? How do we fit into the cancer research ecosystem? 

Barrett: You can categorize cancer research, education and clinical care, and our desire is to be at the top of all those areas. They very much complement each other very well. Relative to research, the biggest aspects are to learn what works (and) what doesn’t work, and to innovate and come up with new approaches. 

I think it’s important to look at a trajectory of the different fields. Within cancer, there’s surgical treatment; there’s medical treatment, which involves chemotherapy, immunotherapy, targeting drugs, but systemic therapy in general; and radiation therapy, which is our specialty, of using high-energy radiation to kill cancer cells. Consider the trajectory of where these skills have come from, to get some aspect of where they’re going. 

Within surgery, there’ve been tremendous advances, particularly around perioperative care: People being as healthy as possible (going) into surgeries, being cared for as carefully as possible after surgery, surgical technique themselves –  the use of fiberoptics and robotic surgery and endoscopic surgeries that are done now are often less invasive than they used to be. So surgery’s advanced tremendously. 

Systemic therapies: Chemotherapy, starting in the 1950s, has been evolving over the years. Effective immunotherapy, mainly in less than the last 15 years, has been very much of a home run for many people diagnosed with even widespread cancers. Targeted drugs avoid some of the systemic effects. 

Within our field or radiotherapy, the advancements in physics have been tremendous: The ability to target tumors, avoid normal tissues, (have) less side effects, higher efficacy. 

The biology is what’s really coming on. The molecular revolution has begun, to be able to better understand the specifics of why some tumors are more or less sensitive to radiation, different doses, different treatment schemes, different complementary treatments given with radiation. 

Frankart: I think speaking broadly, as well as to particular strengths within Cincinnati, is the collaborative nature of cancer research. Each of these advances are not happening in silos, the surgeries advancing on its own, and medical oncology and radiation oncology. 

I think that the best science happens when we’re all communicating and working together so that advances can be synergized. That’s a big focus of what my research is trying to work on; the spatial fractionation is not just thinking about the radiation impact, but what does that do to things like immunotherapy that can optimize outcomes for a patient? The more we think together and collaborate as a discipline, paired with the fact that we have these technologic advances that allow us to ask more complicated and advanced questions, I think is really what’s gonna drive progress in the future. 

Barrett: One of the things we try to emphasize is that while nobody wants this diagnosis of cancer, if you have to face this adversary, we want this to be the very best place in the world to do it. That means that everybody involved in the care is committed, relative to the research, learning what works, what doesn’t work, modifying, and then being innovative – trying to think of new ways, new approaches. 

A lot of things (that) advanced in medicine have been serendipitous, the chance findings. But as they say, fortune is a friend of preparation. So it’s important that our eyes are open all the time, looking for signals or things that may have relevance. 

The atmosphere here in the city is, as Andrew said, highly collaborative, highly collegial. I try to emphasize that when it comes to cancer, even though it’s a competitive world out there, the competition is not each other – the competition is this disease, cancer … 

The advantages of the university include the research infrastructure, where, if we have a burning question, there’s people that can help you try to answer that question. (There is) tons of support for innovative, new ideas. The education is really important in training the next generation of nurses, physicists, therapists, physicians that come through this place. Many of the people working in the city have trained here. Then the clinical care – at the university, we have the advantage of subspecialization, where rather than being a jack of all trades, most oncologists here focus on one or two disease sites, become particularly expert in that area, and then collaborate very closely with the physicians in the different specialties … So we have these, as we call them, multidisciplinary working groups of the physicians in those different areas. They collaborate very closely and coordinate through the plan and carry out the treatment.

Frankart: Another strength I would add on to that is that the research focus that we have is also tied into that multidisciplinary structure. When we’re asking research questions, it’s not just an abstract scientific pursuit of trying to figure out a mechanism of how something works. Oftentimes, we have a particular patient in mind that we’ve treated, and we want to improve something for them. That provides a lot of personal motivation for me, certainly, as to why I want to invest so much time and effort into the research side of things. 

What are your current research projects and what impacts could those projects have down the road? 

Frankart: Ongoing is a clinical trial investigating a specific application of spatial fractionation called lattice therapy. It’s an approach that allows us to give much higher doses than we otherwise could give to large tumors that are causing symptoms for patients, while also allowing it to be a safe treatment, so that there’s minimal side effects associated with it, hopefully. That’s something that’s unique to the region … and it’s as a result of this clinical trial and the grant support. 

The next steps of things I’m working on are ways to inform that treatment planning based upon biology. One of the projects that’s being supported by Ride Cincinnati (a cycling fundraiser) is using MRI studies to look at tumors during a course of radiation and evaluating what changes within a tumor, as opposed to the usual time points of just before and after treatment. If we better understand what’s happening inside of a tumor during radiation therapy, we might be able to better tailor those therapies to individual patients. Also working with colleagues in medical oncology to figure out how that treatment planning with radiation might best be customized to an individual patient, to optimize synergy with things like immunotherapy. 

Barrett: My personal focus has been more in the clinical research side, trying to understand best approaches for diseases that I see the most of, which are genitourinary, particularly prostate cancer, and also had neck cancers … 

The atmosphere we have here is everybody’s getting smarter every day. Part of that is having all the trainees, the students, the residents, the fellows, they’re constantly asking why something’s being done a certain way. That often leads to new ideas. It’s a very dynamic, constantly stimulating atmosphere in medicine in general, particularly in an academic center like this. 

How are government funding cuts affecting cancer research? 

Frankart: Federal funding is a hallmark of what cancer research advances have been driven by, and is, by number, one of the larger funding sources. So whenever there’s uncertainty around that funding, it forces us to be creative in approaches to obtain the funding to do the projects that we want to do. We are fortunate within cancer that it is something that is well supported by other avenues, like private foundations, because it is something that impacts so many people at a personal level. So there’s a lot of enthusiasm for progress to be made in the field. 

Personally, I try to keep an eye both on the traditional federal routes of funding that have been historically relied upon, while also looking out for these other avenues of private support that can fund pilot studies to help us investigate what the right questions are, so we’re more selective about what we’re submitting for federal funding. Or, in some cases, there’s funding sources that are sufficient to allow these projects to go ahead independently. It’s probably more of a change in the balance of where those funds are coming from. But still, trying to make every effort to not slow the progress that overall needs to happen. 

Barrett: Research funding is always a struggle … In terms of what percentage of applied-for grants actually gets funded … historically, it’s been 15 percent or 10 percent, to as low as 5 percent, so it’s always a struggle. It’s a highly competitive process. 

The reality is, though, that people are typically so motivated to advance the fields that many research ideas are, in many respects, unfunded – meaning that people are working on Sundays, unpaid, to advance their ideas. That’s been the spirit of medicine, the spirit of medical science, for many years, and will continue to be, regardless of what the funding opportunities are … 

Andrew mentioned other sources. Ride Cincinnati has been tremendously helpful. It’s an independent entity that funds ideas. Ride Cincinnati has evolved; this will be the 20th year. Initially, it was exclusively designed to fund breast cancer research at the University of Cincinnati, and that’s how it was for the first, at least 10 years. Then it broadened somewhat to include other disease types within the university … exclusive to research. Then in the last year, it broadened further, in two respects. One, to not fund exclusively research, but also to fund educational initiatives and clinical initiatives. And two, to involve not exclusively the university, but the entire community. Every health system, every medical practice, every cancer research organization, every cancer surgery organization in the region was invited to submit grants for funding. There were 28 grants submitted from the community and the university, all of which were funded. 

Frankart: I think that type of community funding is really critical in this funding environment, because the types of questions that those are supporting on the research side fall into a category of pilot studies. (That’s) where you really have an interesting and novel question, but you need some preliminary data to support it for a larger grant application. It’s impossible to have that progress without laying a foundation. So having something like the Ride Cincinnati grant supporting the project I had mentioned is critical, and that data is going to be used in subsequent grant applications. You really need that foundation to be successful overall in the area. 

What do you see in terms of the near future of cancer research as well as the more distant future? What do you see coming down the pipeline? 

Frankart: I think that in the next couple of years, it’s really looking at what Dr. Barrett alluded to. As we better understand the biology, what’s going on inside of tumors, that allows us to customize therapies more to individual patients, and to simply have the technological ability to make those assessments and to tailor treatment plans. Before, we may not have been able to look at that level of granularity of an individual tumor. Even if we could, we may not have the technology to deliver sufficiently distinguishable therapies to be different between patients. We are at a nexus right now where both of those are converging. In the coming years, I think that’ll become particularly manifest. 

In the next decade or so, I think – along a similar theme – as computing power increases, as our understanding of tumors increases, the ability to leverage technology so that we look at an individual patient, individual tumor, individual cells within a patient’s tumor and customize therapy to that, working among all those different specialties within oncology. So that it’s not so much that you come in and are treated for X type of cancer, but you, as an individual, have this that we recommend as your treatment approach, and we have the ability to verify for you that this is the best approach. It may differ from someone who comes in with the exact same diagnosis, because of these features that we can understand at the biology level. 

Barrett: Early detection, I think, is also going to play a bigger role in the very near future. Right now, there are several cancers that are somewhat effectively screened for. But part of this molecular revolution is the ability to, within blood tests and urine tests and stool tests, to detect fragments of tumor cells way before they could ever be detected radiographically or by any clinical examination. That has the opportunity to change things pretty dramatically …

Prevention is really important. There is the latency, meaning that if somebody is exposed to something that may cause a cancer – whether it’s environmental carcinogens, cigarette smoke, chemicals or a virus – it may be five or 10 or 20 or 30 years before the cancer manifests. It’s been very difficult, historically, to track that … 

Through this molecular revolution, (we’ll) be able to better assess potential environmental carcinogens people come into contact with; importance of dietary changes and how that changes cancer prevalence and susceptibility; better understanding the immune system, which has seen an enormous advance in the last 15 years. People have appreciated for well over 100 years the immune system is important in cancer progressing or not. It’s only in the last less than 15 years that there are effective drugs that have allowed people’s immune systems to attack and kill cancer cells that their immune system otherwise couldn’t get to. These drugs are taking away the protective effects that the cancers develop themselves. When it works, it’s dramatic; there are people walking around now, disease-free, who eight years ago flat out would not have been. That’s only going to continue to improve.

How might Cincinnati’s role in cancer research change? Do you see Cincinnati growing in this area? 

Barrett: Very much … One of the things we really try to emphasize in our community here is collegiality, collaboration and an unselfish approach to people working together for the greater good. We have so many resources in this region … We put a lot of effort into bringing these groups together. People who wouldn’t otherwise normally even communicate get to know each other and to potentially have collaborative projects. 

Frankart: I can comment, as an earlier career person in the research field, that it’s very important to feel like you have institutional support to ask big questions and to push things ahead, and not feel like you’re being discouraged from asking those types of things in favor of a status quo. I think that here, there is that significant drive to want to improve things for the patients in front of us. And we recognize that part of doing that is asking those big questions advancing research. So the support that the institution has, that the community has, for that is exactly what you would ask for when you’re thinking about what institutions going ahead are going to be driving research. 

Are there any misconceptions about cancer research out there that you wish that you could clear up? 

Frankart: Thankfully, it’s not something that I’ve personally run into as much, but just the concept of research in general as being more experimental from a patient’s perspective than sometimes it is. Because oftentimes, when we’re going into these projects (as evidenced by the amount that goes into a grant), there’s a lot of foundational science that goes into the questions we’re asking … There’s very logical and ordered steps by the time it gets to something that we’re evaluating in patients. Hopefully, that’s something that increases the level of comfort and enthusiasm for participating in research, and hopefully (patients) viewing it more as an opportunity to access something that’s novel and that we’re excited about, because we wouldn’t bring it to that space if it wasn’t something that we thought could help patients. As opposed to (patients) being worried that we’re trying something that we don’t really have a foundation for. 

Barrett: It’s imperative that we maintain critical thinking, meaning guarding against the hype of a new idea, getting ahead of the true efficacy. That’s where the science of the research is so important – to thoroughly investigate whether something really is safe, is really better, before it gets employed. 

Dr. Barrett, you created the Cincinnati Cancer Foundation. Can you share what led you to create it? 

Barrett: Like a lot of people, (I’m) constantly trying to think of ways that could improve cancer care in the region. About 12 years ago, I saw a 15-year-old guy who had been diagnosed with lymphoma in his neck. To make a long story short, it wound up being a misdiagnosis, and this kid almost got chemotherapy he didn’t need for a disease he didn’t have. How often does this happen? 

In the same week, I saw a patient who had been sent four hours out of town for a disease, but easily could have been taken care of here locally. It spoke to the competition between health systems, where somebody may be referred four hours away, or 12 hours away, rather than across the street … 

I went to the dean of the medical school, and I said, ‘Would you allow me to start an independent second opinion service?’ He said, ‘Well, do your second opinions here.’ I said, ‘We do second opinions here; we’ll continue to. What I’m talking about is something that would be physically, geographically, administratively distinct from the university. I want to do it in Norwood, because it’s a central place in the region. If you Google ‘Cincinnati, Ohio,’ the center of the city, geographically, is the corner of Montgomery Road and Norwood Lateral. So I wanted to rent a space there. He said, ‘how are you going to get paid for it.’ I said, ‘I’m gonna do it for free.’ He said, ‘when are you gonna do it?’ ‘I’m gonna do it on weekends.’ He said, ‘how are you gonna pay for the rent of the space and the equipment?’ I said ‘well, there happens to be a family who wants to support the cancer cause in the region. They think this is a good idea to have second opinions, and they want to do it independently. They don’t want to give to a large organization like University of Cincinnati.’

I went to the university president and said, ‘will you allow me to start an independent foundation for this purpose, and he said, ‘certainly.’ 

That’s how the Cincinnati Cancer Foundation started. That’s how Cincinnati Cancer Advisors started, which is the second opinion entity. I started seeing people on weekends for five years. Never paid myself for this, to this day; my work has been exclusively voluntary … What’s different about this is that so often, if somebody does want a second opinion for their cancer, they go out of town, it’s inconvenient, it’s expensive, the quality is quite variable, there may or may not be communication with the local physician. If somebody goes for multiple opinions, they almost never talk to each other, often just adding confusion from offering conflicting suggestions. Very importantly … second opinions are given widely throughout the country for many diseases, (and) are largely a recruiting tool to recruit patients to that institution for care. I wanted to create something that would be the opposite of all this. There would be no charge whatsoever. Platinum-level, two-hour consultation; immediate communication with the treating oncologist; and no attempt to recruit the patient for care – consultation only … The patients I would see on those weekends, I would suggest they go back where they started, but with the recommendation that may be the same, maybe it’s reassurance. Or maybe it suggests a change in care … 

We’ve grown to six (paid) physicians, some of whom are full time and some are part time. All very senior people, in their ’60s and ’70s, they’re towards the end of their career. They are no longer practicing clinical medicine, in terms of actually treating patients, but now they’re available for their tremendous expertise over 30 to 40 years, and their network of connections they have around the country to ask for people’s opinions on behalf of the patients’ care. So the scenario is that a patient with a newly diagnosed cancer can refer themselves, or be referred by their doctor … 

Prior to their arrival, our physicians have read everything about them from their histories, from their medical records. They spend literally two hours face-to-face with the patient and family; answer every question; immediately call the patients’ treating oncologist. They tell them, ‘I saw your patient, told them they’re great hands with you. And since we had time, we called this expert in Philadelphia who focuses on this cancer. Here is their suggestion, in case you want to incorporate this into your plan.’ 

The idea is to, altruistically, try to raise all the cancer care throughout the region and make it unnecessary in the vast majority of cases for people to leave the region for their care. It’s been very successful. We send surveys to all the patients who’ve been seen, who mostly say it’s the best medical experience they’ve ever had in their life … We send surveys to the physicians, whose patients have been seen. And rather than becoming defensive about possibly being second guessed by this entity, instead, they find it really reassuring that the patient has been told they’re in good hands …  

It’s helpful to the patient in optimizing their plan – our tagline is ‘great care, begins with a great plan.’ It is helpful to the physician to be able to take care of that patient … (and) to take care of other patients they may see in the future (using) what they learned this time around. 

And the whole region now knows that their work may be reviewed by this independent entity, so everybody’s raising their game. 

About a third of the time, there’s complete agreement with the plan that was already in place, just reassurance … About a third of the time, there’s a minor suggested change, a mild and moderate suggested change in plan. About a third of the time, there’s a very significant, suggested change of plan … 

When I started this, I said that an important benchmark would be how often physicians started referring patients to this entity; how often physicians would not feel threatened by this potential second guessing approach. Now, about half of the patients have come referred by physicians. People have embraced it and don’t feel threatened by it, and find it a value-add to the community. 

It exists noplace else in the world. This is the only place in the world where you can get a completely free, no administrative hassle, no pre-certification, no insurance, no hassle whatsoever … 

What allows this thing to be completely independent, completely objective, is the fact it’s not part of a health system, it’s not part of a corporation, it’s not part of an insurance company … So there’s no even potential conflict of interest for the recommendations that people are making. A supportive philanthropic basis is critical, and our city, is, arguably, the most philanthropic city in the country …

How does the work there fit in it all with the research that you all are doing?

Barrett: In the discussions our clinicians have with the clinicians at other places, questions come up constantly, in terms of, would this have been better, would that have been better. With that, ideas are germinated that otherwise might not have occurred. There’s interaction that doesn’t otherwise necessarily happen, because medicine can sometimes be siloed. People get used to working in their health system. This cuts across all that. 

Is there anything else that either of you would want to share about your work specifically or about cancer research in Cincinnati in general? 

Frankart: I’m biased because this is where my clinical area is, but I think another strength and unique aspect to Cincinnati is really the spectrum of how cancer impacts people across ages. Having the expertise at Cincinnati Children’s covering all the way from infants that we treat there, through adulthood over here, and the opportunities that that provides for synergy as well. Knowing that there are certainly biologic differences between pediatric and adult patients and their cancers, but there’s real strengths to each institution that we can lend to each other and advance cancer treatment ways that other cities don’t have that ability to do. 

Barrett: That’s a great point. Also, the example that Children’s Hospital provides, in that we have, literally, the number one children’s hospital in the world right here in Cincinnati. That our city was able to develop that, it certainly is a tremendous example of what can be established in other medical realms and arts. Particularly in cancer; that is our goal, to become the premier. cancer center of the world. Children’s has proven it cat be done here locally … 

One of the things we put a lot of emphasis into is bringing people together from different entities, different industries, that would not normally ever see each other or interact. We’ve had an annual, we call it ‘charge’ against cancer, as opposed to a cancer retreat, of which there are many … 

A couple years ago, we asked people to fantasize about where their field could be, sometime in the future – five, 10, 50, 100 years from now. The way we organize these, typically, is they have competitions between groups of people together. We’ll have 12 groups, eight people in each group, so 96 people, people who don’t know each other and who’ve never worked together from different entities – engineers, biologists, physicists, people from corporations downtown, people from the physics department and main campus, people from DAAP … 

Asking that question, a novel idea that came up was to try to turn the bacteria in people’s intestines, that microbiome as it’s referred to, into cancer-eating bacteria … It got funded that day for $100,000, because the whole group of 96 voted on what they thought the best idea was, and that’s an idea that’s in the process, still, of applying for federal funding; it’s taking root. 

One of the things that’s come out of that is trying to understand why there’s become this epidemic of colon cancer in younger people in this country. Nobody’s had a good answer for it, but there are a lot more young people with colon cancer than there were 20 years ago. This group thinks they may be onto it. There may be a particular substance in certain foods that affect the microbiome in such a way that leads to carcinogenesis. Whether it’s gonna pan out or not, we don’t know. It’s those types of group meetings that originate these new ideas. 

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