LOUISVILLE
The James Graham Brown Cancer Center has a long and successful history in Louisville and the region. According to Brown Cancer Center Director Donald Miller, MD, PhD, that legacy began in 1978 with Wilson Wyatt’s vision for creating the best cancer center in the region, so people did not have to travel outside Louisville or the state for specialty cancer care. The center’s mission is simple, says Miller, “to provide state-of-the-art cancer care for patients in Kentucky.”
That vision expanded in July 2015 when KentuckyOne Health and the University of Louisville (U of L), who jointly operate the Brown Cancer Center, announced the opening of a second cancer center location at Medical Center Jewish Northeast in Louisville’s east end. Miller calls the expansion “a major milestone in extending the mission” of the center.
Mark Milburn, vice president of Oncology Services for KentuckyOne Health, says that partnership and the expansion are helping to bring to fruition the vision set forth by KentuckyOne Health’s president and CEO. “Ruth Brinkley was clear when she came to KentuckyOne that she wanted to expand access to all Kentuckians,” says Milburn.
Medical Center Jewish Northeast was a natural choice for the cancer center’s second physical location because much of the infrastructure was already in place. Chemotherapy infusions were already taking place there, and the outpatient center also had PET scanning, diagnostic, and laboratory capabilities. Additionally, it was a rapidly growing suburban area that serves the northern and eastern edges of Jefferson County, as well as surrounding counties. Milburn says, “We saw it as a growing part of the county that would benefit from these services closer to home.”
Not only does the location off I-265 and Old Henry Road serve a new demographic of patients, it also provides some breathing room for the Brown Cancer Center, which was at capacity at its downtown location.
Rooted in Multidisciplinary Care
If there is an overarching philosophy for Brown Cancer Center services, it is multidisciplinary care. “All care at the Brown Cancer Center is multidisciplinary, meaning we have a team of physicians for each different tumor type,” says Miller.
Medical oncologist Beth Riley, MD, FACP, concurs, “We pride ourselves on multidisciplinary care at the Brown Cancer Center, and we’re trying to preserve specialty care at the Northeast location as well.” Riley is the director of the Breast Cancer Multidisciplinary Clinic and director of Clinical Operations at the Brown Cancer Center, and will oversee cancer services at Medical Center Jewish Northeast.
The team at Medical Center Jewish Northeast is made up of six medical oncologists and one radiation oncologist, all with University of Louisville Physicians. Currently, the center’s plan is to start all patients at the downtown location for their initial visit and evaluation in the multidisciplinary clinics to form a treatment plan. Once the plan is formed, patients can choose to have chemotherapy treatments and follow-ups at Medical Center Jewish Northeast because it is closer to their home or work, or simply because they value the ease of parking and access and the greener surroundings (treatment area windows open to views of green fields and trees rather than urban buildings) of the suburban location. Each patient will be discussed at the multidisciplinary tumor conferences downtown, getting the benefit of the entirety of the cancer center’s expertise.
The new location will provide chemotherapy; radiology follow-up, such as CT scans, PET scans, and bone density; and consultations with a radiation oncologist. In the near future, executives and physician leaders hope to add radiation therapy services, clinical trials, a second opinion clinic, and a patient resource center to the Northeast location.
“The primary goal of the new location is to grow the program and to be a destination for referrals,” says Miller. “By the end of two years, we hope to see as many as 25 patients a day at Northeast.” Milburn concurs, adding the goal also includes providing “access to that level of subspecialty care closer to home.”
“We have a strong translational research program at the Brown Cancer Center and a lot of unique clinical trials that go through our multidisciplinary clinics. Eventually our goal is to get clinical trial treatments at Medical Center Jewish Northeast that would not be available at other places,” says Miller.
Clinical Research Provides Novel Therapies for Kentucky, the World
The goal of the Brown Cancer Center’s clinical trial program is simple on principle but monumental in execution. Says Jason Chesney, MD, PhD, deputy director of the Brown Cancer Center, “Our goal is to reduce cancer morbidity in the state and globally.”
The opening of a second cancer center location is a stepping stone towards that goal. “The expansion of the Brown Cancer Center to Jewish Northeast means a lot for research and clinical trials and patient access. It will make available the 150 clinical trials open at the Brown Cancer Center right now. But we are also expanding the clinical research program to include Catholic Health Initiatives Institute for Research and Innovation (CIRI) where our medical oncologists will accrue patients to nationwide trials at the northeast site. That’s another 100 trials,” says Chesney.
The center’s execution of its mission is two-pronged – to develop new therapeutics and improve detection while cancer is at a more curable stage – and the timing could not be more appropriate. “Right now there’s a revolution occurring in oncology. Up to the last several years we’ve used surgery, chemotherapy, and radiation to treat cancer. We had some improvements in survival and quality of life, but we’ve not had the transformative moment where we can markedly reduce cancer-related deaths, and that’s changing right now,” says Chesney.
Chesney points to two new classes of drugs: immune checkpoint inhibitors and oncolytic viruses. Immune checkpoint inhibitors block the antibodies that turn off the immune system. MD-UPDATE discussed two immune checkpoint inhibitors that target the checkpoint dubbed PD-1 in last year’s oncology issue #89. Since that time, two PD-1 inhibitors, pembrolizumab (Keytruda®) and nivolumab (Opdivo®), have been FDA approved for both melanoma and lung cancer. “What started in melanoma is spreading across multiple solid and liquid cancer types. The most recent data shows they are effective in colon, liver, breast, and head and neck cancers,” says Chesney. “I believe these two drugs are going to reduce cancer-related deaths in the US by about 15 percent.”
Oncolytic viruses, which are injected directly into tumors, act as an accelerator to stimulate the immune system. “We’re seeing dramatic results with just the oncolytic virus itself. If you add the oncolytic viruses and immune checkpoint inhibitors together, we’re seeing synergistic improvements in activity in terms of tumor regression and survival,” says Chesney.
Right now, the Brown Cancer Center is the number one site in the country for a trial of an oncolytic virus called TVEC with the immune checkpoint inhibitor ipilimumab (Yervoy®) in melanoma. Chesney says, “One hundred percent of patients are responding,” which is unheard of in cancer treatment.
The center is also working with industry sponsor Amgen to test the combination concept in multiple cancer types. They are opening a phase 1 trial to directly inject liver metastases with the oncolytic virus for the treatment of multiple cancer types including cancers of the lung, breast, colon, kidney, pancreas, and liver. The next step will be combining liver injections with PD-1 inhibitors.
“The importance of these trials for stage 4 cancer cannot be overstated. These trials are the one treatment modality that gives these patients hope for long-term survival,” says Chesney. And improving access and enrollment is a critical component of addressing cancer mortality. “Right now the estimate is that three percent of adult cancer patients enroll in clinical trials. That needs to go to 50 or 75 percent,” says Chesney. Comparatively 70 percent of pediatric cancer patients enroll in trials. “It’s my belief if you can’t tell a patient you have a more than 75 percent chance of curing them with the current regimens, then you should put them on a clinical trial,” says Chesney.
Another exciting aspect of the Brown Cancer Center’s research program is the use of tobacco to make cancer vaccines. The center has two vaccines going into early phase clinical trials in the next year to 18 months – one for cervical cancer and one for colon cancer. Miller describes them as “one of a kind in the world” and says they are oral agents that should be much less expensive than current treatments. “We think that will be important worldwide,” he says.
Breast Cancer Multidisciplinary Clinic
Breast cancer is the most common cancer in women. Thankfully, advances in mammography, genetic testing, and new therapies are changing the way clinicians fight breast cancer.
The Breast Cancer Multidisciplinary Clinic at the Brown Cancer Center has recently added new practitioners and technology to fight the disease. New physicians include a specialty fellowship-trained breast surgeon, Nicolas Ajkay, MD, who has been with the center for about a year and adds a new layer of expertise to the team, and a new medical oncology partner, Mounika Mandadi, MD.
New technology includes the addition of tomosynthesis, or 3D mammography, in the diagnostic breast center at the Brown Cancer Center. Tomosynthesis is a new option in breast cancer screening that may enhance the detection of early breast cancers. However Riley cautions, “Despite new advances, we still have a problem with at-risk women not receiving timely mammograms.” She encourages physicians to adhere to American Cancer Society screening guidelines, which say discussions should start at age 40, and all women should have regular screening by age 50.
Advances in genetic testing have identified genes that were not recognized just five years ago. “The field of genetics in the last couple of years has really expanded in terms of genetic testing available, as well as identified genes, which we now recognize put people at risk for breast cancer,” says Riley. Patients who screened negative for BRCA1 and BRCA2 in the past but have a strong family history should consider rescreening for newly identified genes, such as PALB2. Genetic screening is available at the Brown Cancer Center, and genetic counselors are part of the center’s multidisciplinary clinics.
Clinical trials through the breast clinic are growing, and that means increased access to new developments. “We are working on bringing novel therapies, including immune therapies, in the form of clinical trials to patients. This includes what I call ‘homegrown’ drugs that were developed by scientists here at the Brown Cancer Center,” says Riley. The short-term goal is to extend these trials to patients at Medical Center Jewish Northeast.
Lung Cancer Multidisciplinary Clinic
Kentucky leads the nation in lung cancer deaths, and medical oncologist/hematologist Goetz Kloecker, MD, MBA, MSPH, FACP, says this translates to hundreds of new lung cancer patients for the Brown Cancer Center each year. Luckily, advances in screening and treatment of lung cancer are also on the rise. “There’s a tsunami of research and progress right now,” says Kloecker, who is director of the Lung Cancer Multidisciplinary Clinic and fellowship program director for Oncology/Hematology.
As with breast cancer, the fight against lung cancer begins with screening. The Brown Cancer Center began its lung cancer screening program three years ago, before it became standard of care. Since then, 17 KentuckyOne Health facilities, including Brown Cancer Center, have been recognized as Lung Cancer Alliance Screening Centers of Excellence.
Kloecker says the problem with lung cancer is that 60–70 percent of cancers are found at an advanced stage of 3 or 4, rather than the curable stages 1 and 2. “Low-dose CT scans are very sensitive to find little nodules and early cancers not found by chest x-ray,” says Kloecker. “By doing a screening CT, you find it in the early stage and can remove it and have a much better change of curing it. That’s why mortality is reduced by 20 percent.”
On the horizon, Kloecker says the Brown Cancer Center is working on a breath test and a blood test for lung cancer detection. The breath test analyzes chemicals exhaled in the breath to predict if a lung nodule is cancerous. The blood test evaluates the calorimetric profiles of blood plasma to detect cancer.
When it comes to treatment, the multidisciplinary clinic’s philosophy relies heavily on clinical trials to provide novel therapies. “We want to try new treatments and medications to get results better than the standard of care,” says Kloecker.
There are two immunotherapy drugs FDA-approved for lung cancer – pembrolizumab and nivolumab. “The treatment makes it impossible for cancer cells to hide from the immune system, so immune cells can attack it and slow the disease down and cause remission where all others have failed,” says Kloecker. He also points to one particular treatment for squamous cell carcinoma that doubles life expectancy in patients who already failed chemotherapy and other traditional treatments.
The discovery of oncogene mutations that initiate cancer has led to the creation of targeted therapies that are often as simple as taking a pill to achieve remission. “Unfortunately, we haven’t identified oncogenes in the majority of patients. It’s about 10 to 15 percent of the population where we can start with a pill to shut down cancer,” says Kloecker, but he is still encouraged by the prospects.
As part of a grant, the Brown Cancer Center is in the second year of a study exploring ways to improve lung cancer care in Kentucky. Unfortunately, one of the big challenges is that 20–35 percent of patients with stage 4 lung cancer do not get treatment. But there is a misconception that these patients are limited to rural areas of the state. “I can tell you it happens in non-Appalachian areas and urban areas. The stereotypes are not true. Untreated lung cancer patients are out there in the cities too,” says Kloecker.
The project includes analysis of why patients are not getting treatment (whether it be access, stigma, or the fatalism of patients or providers) and efforts to educate providers on the myths and facts of treatment advances. “Once primary care physicians and providers see that, it will hopefully change referral patterns, and the enthusiasm of physicians will transfer to patients,” says Kloecker.
The Power and Synergy of a Regional Network
The KentuckyOne Health and U of L partnership is particularly fruitful in cancer care, where the breadth of KentuckyOne’s reach throughout the state, coupled with U of L’s expertise and research portfolio, are making huge strides. “Our ancillary programs have seen the benefit. We have a single cancer registry across KentuckyOne,” says Milburn, which has increased efficiency of data collection and submission.
Both Miller and Milburn point to the synergies between community and academic physicians as a benefit of the collaboration. Milburn says part of the leadership team’s job is introducing these physicians to one another to provide optimal care. An area Milburn is particularly proud of is specialty pharmacy. “We’ve worked hard to create specialty pharmacy programming with guidance from the Brown Cancer Center and from community-based physicians,” he says. Having their own specialty pharmacy program allows them critical input and ultimately more control over outcomes in a growing area of cancer treatment.
Another example of the synergy is unified leadership. “All of our cancer programming is under the same operational leader, Nancy Bowles,” says Milburn. “We have confidence we are providing the same level of quality everywhere because it is being overseen by the same leader across all facilities.” Physician leadership and oversight is also an important component of their success.
Education of patients and providers remains a priority. To continue to spread the word about advances in cancer detection and treatment, the Brown Cancer Center is expanding its website for patients and partnering with KentuckyOne to access their statewide network of referrals through primary care clinics and emergency departments.
Whether it be in prevention, detection, or treatment, the James Graham Brown Cancer Center is on the forefront of a transformative moment in cancer care. Its commitment to expand access to all Kentuckians and make discoveries that impact global cancer morbidity and mortality are certainly worthy of its mission.
Right now there’s a revolution occurring in oncology. Up to the last several years … we’ve not had the transformative moment where we can markedly reduce cancer-related deaths, and that’s changing right now.
Patients who screened negative for BRCA1 and BRCA2 in the past but have a strong family history of breast cancer should consider rescreening for newly identified genes, such as PALB2.